FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Neckers, L
Ricketts, CJ
Linehan, WM
AF Neckers, Len
Ricketts, Christopher J.
Linehan, W. Marston
TI New Insights into von Hippel-Lindau Function Highlighted by
Investigation of the Trichloroethylene-Induced p.P81S Hotspot Mutation
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID RENAL-CELL CARCINOMA; TUMOR-SUPPRESSOR GENE; CANCER; EXPOSURE
C1 [Neckers, Len; Ricketts, Christopher J.; Linehan, W. Marston] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, CRC Room 1W-5940,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM WML@nih.gov
FU Intramural NIH HHS
NR 14
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 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-. Natl. Cancer Inst.
PD SEP
PY 2013
VL 105
IS 18
BP 1339
EP 1340
DI 10.1093/jnci/djt240
PG 2
WC Oncology
SC Oncology
GA 232GH
UT WOS:000325479900003
PM 23990664
ER
PT J
AU Amiri-Kordestani, L
Kamangar, F
Zujewski, JA
AF Amiri-Kordestani, Laleh
Kamangar, Farin
Zujewski, Jo Anne
TI Inflammatory Breast Cancer: Yet Another Risk of the Obesity Epidemic?
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID EXPRESSION; CARCINOMA; SUBTYPES; DENSITY
C1 [Amiri-Kordestani, Laleh; Zujewski, Jo Anne] NCI, Med Oncol Branch, Ctr Canc Res, Rockville, MD 20850 USA.
[Kamangar, Farin] Morgan State Univ, Sch Community Hlth & Policy, Baltimore, MD 21239 USA.
RP Zujewski, JA (reprint author), NCI, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
EM zujewskj@mail.nih.gov
NR 21
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 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-. Natl. Cancer Inst.
PD SEP
PY 2013
VL 105
IS 18
BP 1340
EP 1342
DI 10.1093/jnci/djt236
PG 4
WC Oncology
SC Oncology
GA 232GH
UT WOS:000325479900004
PM 24046389
ER
PT J
AU Schmitz, KH
Neuhouser, ML
Agurs-Collins, T
Zanetti, KA
Cadmus-Bertram, L
Dean, LT
Drake, BF
AF Schmitz, Kathryn H.
Neuhouser, Marian L.
Agurs-Collins, Tanya
Zanetti, Krista A.
Cadmus-Bertram, Lisa
Dean, Lorraine T.
Drake, Bettina F.
TI Impact of Obesity on Cancer Survivorship and the Potential Relevance of
Race and Ethnicity
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Review
ID QUALITY-OF-LIFE; BODY-MASS INDEX; STAGE BREAST-CANCER; POPULATION-BASED
SAMPLE; IOWA WOMENS HEALTH; LONG-TERM BREAST; AFRICAN-AMERICAN;
PROSTATE-CANCER; PHYSICAL-ACTIVITY; RISK-FACTORS
AB Evidence that obesity is associated with cancer incidence and mortality is compelling. By contrast, the role of obesity in cancer survival is less well understood. There is inconsistent support for the role of obesity in breast cancer survival, and evidence for other tumor sites is scant. The variability in findings may be due in part to comorbidities associated with obesity itself rather than with cancer, but it is also possible that obesity creates a physiological setting that meaningfully alters cancer treatment efficacy. In addition, the effects of obesity at diagnosis may be distinct from the effects of weight change after diagnosis. Obesity and related comorbid conditions may also increase risk for common adverse treatment effects, including breast cancer-related lymphedema, fatigue, poor health-related quality of life, and worse functional health. Racial and ethnic groups with worse cancer survival outcomes are also the groups for whom obesity and related comorbidities are more prevalent, but findings from the few studies that have addressed these complexities are inconsistent. We outline a broad theoretical framework for future research to clarify the specifics of the biological-social-environmental feedback loop for the combined and independent contributions of race, comorbid conditions, and obesity on cancer survival and adverse treatment effects. If upstream issues related to comorbidities, race, and ethnicity partly explain the purported link between obesity and cancer survival outcomes, these factors should be among those on which interventions are focused to reduce the burden of cancer.
C1 [Schmitz, Kathryn H.; Dean, Lorraine T.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Neuhouser, Marian L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Agurs-Collins, Tanya; Zanetti, Krista A.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Cadmus-Bertram, Lisa] Univ Calif San Diego, Moores Canc Ctr, San Diego, CA 92103 USA.
[Drake, Bettina F.] Washington Univ, Dept Surg, St Louis, MO USA.
RP Schmitz, KH (reprint author), Univ Penn, Perelman Sch Med, 423 Guardian Dr,8th Fl Blockley Hall, Philadelphia, PA 19104 USA.
EM schmitz@upenn.edu
OI Drake, Bettina/0000-0001-9340-5848
FU National Institutes of Health [U54-CA155850, U01CA116850, 1U54CA155435,
U54 CA155496]
FX This work was supported by grants from the National Institutes of Health
(U54-CA155850 at University of Pennsylvania [KHS, LTD]; U01CA116850 at
the Fred Hutchinson Cancer Research Center [MLN]; 1U54CA155435 at
University of California at San Diego [LC-B]; and U54 CA155496 at
Washington University [BFD]).
NR 138
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U1 3
U2 17
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-. Natl. Cancer Inst.
PD SEP
PY 2013
VL 105
IS 18
BP 1344
EP 1354
DI 10.1093/jnci/djt223
PG 11
WC Oncology
SC Oncology
GA 232GH
UT WOS:000325479900006
PM 23990667
ER
PT J
AU Schairer, C
Li, Y
Frawley, P
Graubard, BI
Wellman, RD
Buist, DSM
Kerlikowske, K
Onega, TL
Anderson, WF
Miglioretti, DL
AF Schairer, Catherine
Li, Yan
Frawley, Peter
Graubard, Barry I.
Wellman, Robert D.
Buist, Diana S. M.
Kerlikowske, Karla
Onega, Tracy L.
Anderson, William F.
Miglioretti, Diana L.
TI Risk Factors for Inflammatory Breast Cancer and Other Invasive Breast
Cancers
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID BODY-MASS INDEX; DENSITY
AB Background We investigated risk factors for inflammatory breast cancer (IBC), a rare, aggressive, and poorly understood breast cancer that is characterized by diffuse breast skin erythema and edema.
Methods We included 617 IBC case subjects in a nested case-control study from the Breast Cancer Surveillance Consortium database (1994-2009). We also included 1151 noninflammatory, locally advanced, invasive breast cancers with chest wall/breast skin involvement (LABC), 7600 noninflammatory invasive case subjects without chest wall/breast skin involvement (BC), and 93 654 control subjects matched to case subjects on age and year at diagnosis and mammography registry. We present estimates of rate ratios (RRs) and 95% confidence intervals (CI) from conditional logistic regression analyses for each case group vs control subjects based on multiply imputed datasets.
Results First-degree family history of breast cancer and high mammographic breast density increased risk of IBC, LABC, and BC. High body mass index (BMI) increased IBC risk irrespective of menopausal status and estrogen receptor (ER) expression; rate ratios for BMI 30 and greater vs BMI less than 25 were 3.90 (95% CI = 1.50 to 10.14) in premenopausal women and 3.70 (95% CI = 1.98 to 6.94) in peri/postmenopausal women not currently using hormones. BMI 30 and greater slightly increased risk of ER-positive BC (RR = 1.40; 95% CI = 1.11 to 1.76). Statistically significant reductions in risk of ER-negative IBC with older age at first birth and of ER-positive IBC with higher education were not seen for LABC and BC of the same ER status.
Conclusions Different associations with BMI, age at first birth, and education between IBC and/or LABC and BC suggest a distinct etiology for IBC.
C1 [Li, Yan] Univ Maryland, Joint Program Survey Methodol, College Pk, MD 20742 USA.
[Frawley, Peter; Wellman, Robert D.; Buist, Diana S. M.; Miglioretti, Diana L.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Schairer, Catherine; Graubard, Barry I.; Anderson, William F.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Kerlikowske, Karla] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Kerlikowske, Karla] Univ Calif San Francisco, Dept Epidemiol Biostat, San Francisco, CA 94143 USA.
[Onega, Tracy L.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA.
[Miglioretti, Diana L.] Univ Calif Davis Sch Med, Dept Publ Hlth Sci, Davis, CA USA.
RP Schairer, C (reprint author), NCI, 9609 Med Ctr Dr,Rm 7E612, Bethesda, MD 20892 USA.
EM schairec@exchange.nih.gov
FU National Cancer Institute [U01CA63740, U01CA86076, U01CA86082,
U01CA63736, U01CA70013, U01CA69976, U01CA63731, U01CA70040,
HHSN261201100031C]; Intramural Research Program at the National Cancer
Institute, National Institutes of Health
FX This work was supported by the National Cancer Institute-funded BCSC
(U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976,
U01CA63731, U01CA70040, HHSN261201100031C) and by the Intramural
Research Program at the National Cancer Institute, National Institutes
of Health.
NR 23
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U1 0
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-. Natl. Cancer Inst.
PD SEP
PY 2013
VL 105
IS 18
BP 1373
EP 1384
DI 10.1093/jnci/djt206
PG 12
WC Oncology
SC Oncology
GA 232GH
UT WOS:000325479900009
PM 24046390
ER
PT J
AU Ellis, RJ
Boufraqech, M
Jain, M
Patel, D
Nilubol, N
He, M
Zhang, LS
Kebebew, E
AF Ellis, Ryan J.
Boufraqech, Myriem
Jain, Meenu
Patel, Dhaval
Nilubol, Naris
He, Mei
Zhang, Lisa
Kebebew, Electron
TI Programmed Death-Ligand 1 as a prognostic marker in papillary thyroid
cancer
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Meeting Abstract
CT 99th Annual Clinical Congress of the American-College-of-Surgeons / 68th
Annual Sessions of the Owen H Wangensteen Surgical Forum on Fundamental
Surgical Problems
CY OCT 06-10, 2013
CL Washington, DC
SP Amer Coll Surg
C1 [Ellis, Ryan J.; Boufraqech, Myriem; Jain, Meenu; Patel, Dhaval; Nilubol, Naris; He, Mei; Zhang, Lisa; Kebebew, Electron] NCI, Bethesda, MD 20892 USA.
RI Boufraqech, Myriem/E-4823-2016
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
EI 1879-1190
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD SEP
PY 2013
VL 217
IS 3
SU S
BP S30
EP S30
PG 1
WC Surgery
SC Surgery
GA 233OG
UT WOS:000325577900044
ER
PT J
AU Upham, TC
Rao, M
Atay, SM
Siddiqui, MM
Hong, YK
Raiji, MT
Hong, JA
Zhang, MR
Linehan, WM
Schrump, DS
AF Upham, Trevor C.
Rao, Mahadev
Atay, Scott M.
Siddiqui, M. Minhaj
Hong, Young K.
Raiji, Manish T.
Hong, Julie A.
Zhang, Mary R.
Linehan, W. Martson
Schrump, David S.
TI Cigarette smoke modulates glucose utilization in human lung cancer cells
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Meeting Abstract
CT 99th Annual Clinical Congress of the American-College-of-Surgeons / 68th
Annual Sessions of the Owen H Wangensteen Surgical Forum on Fundamental
Surgical Problems
CY OCT 06-10, 2013
CL Washington, DC
SP Amer Coll Surg
C1 [Upham, Trevor C.; Rao, Mahadev; Atay, Scott M.; Siddiqui, M. Minhaj; Hong, Young K.; Raiji, Manish T.; Hong, Julie A.; Zhang, Mary R.; Linehan, W. Martson; Schrump, David S.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
EI 1879-1190
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD SEP
PY 2013
VL 217
IS 3
SU S
BP S40
EP S41
PG 4
WC Surgery
SC Surgery
GA 233OG
UT WOS:000325577900069
ER
PT J
AU O'Seaghdha, CM
Hwang, SJ
Ho, JE
Vasan, RS
Levy, D
Fox, CS
AF O'Seaghdha, Conall M.
Hwang, Shih-Jen
Ho, Jennifer E.
Vasan, Ramachandran S.
Levy, Daniel
Fox, Caroline S.
TI Elevated Galectin-3 Precedes the Development of CKD
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE; PLASMA TOTAL
HOMOCYSTEINE; ALL-CAUSE MORTALITY; HEART-FAILURE; RENAL-INSUFFICIENCY;
DIABETES-MELLITUS; CARDIOVASCULAR-DISEASE; GENERAL-POPULATION;
BLOOD-PRESSURE
AB Galectin-3, a profibrotic mediator, is linked to the development of renal fibrosis in animal models and inversely correlates with GFR in humans, but whether galectin-3 predicts incident kidney disease is unknown. Here, we assessed renal outcomes for 2450 Framingham Offspring participants who attended examination 6 (1995-1998) and had follow-up data at examination 8 (2005-2008). Renal outcomes of interest included rapid decline in renal function (3 ml/min per 1.73 m(2) per year decline in estimated GFR [eGFR]), CKD (eGFR < 60 ml/min per 1.73 m(2)), and albuminuria (albumin-to-creatinine ratio 17 mg/g in men or 25 mg/g in women). We used multivariable logistic regression models to evaluate associations between galectin-3 with incident renal outcomes at examination 8. During a mean follow-up of 10.1 years, GFR declined rapidly in 241 (9.2%) participants, incident CKD developed in 277 (11.3%), and albuminuria developed in 194 (10.1%). Higher plasma levels of galectin-3 were associated with rapid decline in eGFR (per 1-SD log-galectin-3; adjusted odds ratio [OR], 1.49; 95% confidence interval [CI], 1.28 to 1.73]) and a higher risk of incident CKD (OR, 1.47; 95% CI, 1.27 to 1.71), but not with the risk of incident albuminuria. The addition of galectin-3 to clinical predictors improved the C-statistic (0.837-0.845; P=0.02) but did not reach predefined thresholds for clinically significant improvements to risk prediction based on reclassification indices. In conclusion, elevated levels of plasma galectin-3 are associated with increased risks of rapid GFR decline and of incident CKD in the community, which calls for further study in higher-risk groups.
C1 [O'Seaghdha, Conall M.; Hwang, Shih-Jen; Ho, Jennifer E.; Vasan, Ramachandran S.; Levy, Daniel; Fox, Caroline S.] NHLBI, Intramural Res Program, Framingham Heart Study, Framingham, MA 01702 USA.
[O'Seaghdha, Conall M.; Hwang, Shih-Jen; Ho, Jennifer E.; Vasan, Ramachandran S.; Levy, Daniel; Fox, Caroline S.] Ctr Populat Studies, Bethesda, MD USA.
[O'Seaghdha, Conall M.] Massachusetts Gen Hosp, Div Renal, Boston, MA 02114 USA.
[Ho, Jennifer E.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
[O'Seaghdha, Conall M.] Beaumont Hosp, Div Nephrol & Transplantat, Dublin 9, Ireland.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Sect Cardiol & Prevent Med, Boston, MA 02118 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Epidemiol Sect, Boston, MA 02118 USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA.
RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM foxca@nhlbi.nih.gov
OI Ho, Jennifer/0000-0002-7987-4768; Ramachandran,
Vasan/0000-0001-7357-5970
FU National Heart, Lung, and Blood Institute [N01-HC-25195]; American Heart
Association
FX The Framingham Heart Study is supported by the National Heart, Lung, and
Blood Institute (N01-HC-25195). J.E.H. is supported by an American Heart
Association Clinical Research Program award.
NR 69
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U2 11
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 SEP
PY 2013
VL 24
IS 9
BP 1470
EP 1477
DI 10.1681/ASN.2012090909
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 227EO
UT WOS:000325092900018
PM 23766533
ER
PT J
AU Miller, LR
AF Miller, Lara R.
TI Lymphatic Function and the Immune Response to Microbial or Viral
Infection
SO LYMPHATIC RESEARCH AND BIOLOGY
LA English
DT Article
AB The National Institute of Allergy and Infectious Diseases (NIAID) is the primary institute within the National Institutes of Health (NIH) that conducts and supports basic and applied research to better understand, treat, and ultimately prevent infectious, immunologic, and allergic diseases. For more than 60 years, NIAID research has led to new therapies, vaccines, diagnostic tests, and other technologies that have improved the health of millions of people in the United States and around the world.
C1 [Miller, Lara R.] NIAID, Basic Immunol Branch, Div Allergy Immunol & Transplantat, NIH,DHHS, Bethesda, MD 20892 USA.
RP Miller, LR (reprint author), NIAID, Basic Immunol Branch, Div Allergy Immunol & Transplantat, 6610 Rockledge Dr,Room 6307, Bethesda, MD 20892 USA.
EM lrmiller@niaid.nih.gov
FU The National Institute of Allergy and Infectious Diseases (NIAID);
National Institutes of Health (NIH)
FX The National Institute of Allergy and Infectious Diseases (NIAID) is the
primary institute within the National Institutes of Health (NIH) that
conducts and supports basic and applied research to better understand,
treat, and ultimately prevent infectious, immunologic, and allergic
diseases. For more than 60 years, NIAID research has led to new
therapies, vaccines, diagnostic tests, and other technologies that have
improved the health of millions of people in the United States and
around the world.
NR 0
TC 0
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U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1539-6851
EI 1557-8585
J9 LYMPHAT RES BIOL
JI Lymphat. Res. Biol.
PD SEP 1
PY 2013
VL 11
IS 3
SI SI
BP 116
EP 116
DI 10.1089/lrb.2013.0010
PG 1
WC Medicine, Research & Experimental; Physiology
SC Research & Experimental Medicine; Physiology
GA 219AY
UT WOS:000324477300002
PM 24024575
ER
PT J
AU Nutman, TB
AF Nutman, Thomas B.
TI Insights into the Pathogenesis of Disease in Human Lymphatic Filariasis
SO LYMPHATIC RESEARCH AND BIOLOGY
LA English
DT Article
ID HUMAN BANCROFTIAN FILARIASIS; ADULT WUCHERERIA-BANCROFTI;
PARASITE-SPECIFIC ANERGY; BRUGIA-MALAYI; ENDEMIC AREA; T-CELLS;
ULTRASONOGRAPHIC EVIDENCE; INFLAMMATORY RESPONSES; TISSUE-FLUID; SCROTAL
AREA
AB Although two thirds of the 120 million people infected with lymph-dwelling filarial parasites have subclinical infections, approximate to 40 million have lymphedema and/or other pathologic manifestations including hydroceles (and other forms of urogenital disease), episodic adenolymphangitis, lymphedema, and (in its most severe form) elephantiasis. Adult filarial worms reside in the lymphatics and lymph nodes and induce lymphatic dilatation. Progressive lymphatic damage and pathology results primarily from the host inflammatory response to the parasites but also perhaps from the host inflammatory response to the parasite's Wolbachia endosymbiont and as a consequence of superimposed bacterial or fungal infections. This review will attempt to shed light on disease pathogenesis in lymphatic filariasis.
C1 [Nutman, Thomas B.] NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA.
RP Nutman, TB (reprint author), Bldg 4,Room B1-03,4 Ctr Dr, Bethesda, MD 20892 USA.
EM tnutman@niaid.nih.gov
FU Intramural Research Program of the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX This work was supported by the Intramural Research Program of the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health.
NR 59
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U1 1
U2 17
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1539-6851
EI 1557-8585
J9 LYMPHAT RES BIOL
JI Lymphat. Res. Biol.
PD SEP 1
PY 2013
VL 11
IS 3
SI SI
BP 144
EP 148
DI 10.1089/lrb.2013.0021
PG 5
WC Medicine, Research & Experimental; Physiology
SC Research & Experimental Medicine; Physiology
GA 219AY
UT WOS:000324477300007
PM 24044755
ER
PT J
AU Samuel-Hodge, CD
Garcia, BA
Johnston, LF
Gizlice, Z
Ni, A
Cai, JW
Kraschnewski, JL
Gustafson, AA
Norwood, AF
Glasgow, RE
Gold, AD
Graham, JW
Evenson, KR
Trost, S
Keyserling, TC
AF Samuel-Hodge, Carmen D.
Garcia, Beverly A.
Johnston, Larry F.
Gizlice, Ziya
Ni, Andy
Cai, Jianwen
Kraschnewski, Jennifer L.
Gustafson, Alison A.
Norwood, Arnita F.
Glasgow, Russell E.
Gold, Alison D.
Graham, John W.
Evenson, Kelly R.
Trost, Stewart
Keyserling, Thomas C.
TI Translation of a Behavioral Weight Loss Intervention for Mid-life,
Low-Income Women in Local Health Departments
SO OBESITY
LA English
DT Article
ID PHYSICAL-ACTIVITY; RANDOMIZED-TRIAL; PRIMARY-CARE; RURAL COMMUNITIES;
CLINICAL-TRIAL; RISK-FACTORS; OBESITY; ADULTS; MANAGEMENT; US
AB Objective: To translate a behavioral weight loss intervention for mid-life, low-income women in real world settings.
Design and Methods: In this pragmatic clinical trial, we randomly selected six North Carolina county health departments and trained their current staff to deliver a 16-session evidence-based behavioral weight loss intervention (special intervention, SI). SI weight loss outcomes were compared to a delayed intervention (DI) control group.
Results: Of 432 women expressing interest, 189 completed baseline measures and were randomized within health departments to SI (N = 126) or DI (N = 63). At baseline, average age was 51 years, 53% were African American, mean weight was 100 kg, and BMI averaged 37 kg/m(2). A total of 96 (76%) SI and 55 (87%) DI participants returned for 5-month follow-up measures. The crude weight change was -3.1 kg in the SI and -0.4 kg in the DI group, for a difference of 2.8 kg (95% CI 1.4 to 4.1, p = 0.0001). Diet quality and physical activity improved significantly more in the SI group, and estimated intervention costs were $327 per participant.
Conclusion: This pragmatic short-term weight loss intervention targeted to low-income mid-life women yielded meaningful weight loss when translated to the county health department setting.
C1 [Samuel-Hodge, Carmen D.] Univ N Carolina, Dept Nutr, Gillings Sch Publ Hlth, Chapel Hill, NC 27599 USA.
[Samuel-Hodge, Carmen D.] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
[Samuel-Hodge, Carmen D.; Garcia, Beverly A.; Johnston, Larry F.; Gizlice, Ziya; Norwood, Arnita F.; Keyserling, Thomas C.] Univ N Carolina, UNC Ctr Hlth Promot & Dis Prevent, Chapel Hill, NC USA.
[Cai, Jianwen] Univ N Carolina, Dept Biostat, Gillings Sch Publ Hlth, Chapel Hill, NC USA.
[Kraschnewski, Jennifer L.] Penn State Coll Med, Div Gen Internal Med, Hershey, PA USA.
[Gustafson, Alison A.] Univ Kentucky, Dept Nutr, Lexington, KY USA.
[Glasgow, Russell E.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA.
[Gold, Alison D.] Hudson River Healthcare Inc, New York, NY USA.
[Graham, John W.] Univ N Carolina, NC Inst Publ Hlth, Chapel Hill, NC USA.
[Evenson, Kelly R.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Trost, Stewart] Oregon State Univ, Dept Nutr & Exercise Sci, Corvallis, OR 97331 USA.
[Keyserling, Thomas C.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA.
RP Samuel-Hodge, CD (reprint author), Univ N Carolina, Dept Nutr, Gillings Sch Publ Hlth, Chapel Hill, NC 27599 USA.
EM carmen_samuel@unc.edu
RI Trost, Stewart/B-5948-2012
OI Trost, Stewart/0000-0001-9587-3944
FU Centers for Disease Control and Prevention (CDC) [5R18DP001144];
University of North Carolina Center for Health Promotion and Disease
Prevention (a CDC prevention research center) through by CDC cooperative
agreement [U48/DP000059]
FX This study was supported through funding by the Centers for Disease
Control and Prevention (CDC) grant No. 5R18DP001144. Other support was
provided by the University of North Carolina Center for Health Promotion
and Disease Prevention (a CDC prevention research center) through
funding by CDC cooperative agreement No. U48/DP000059. These funding
sources had no involvement with the preparation of this manuscript or
the decision to submit for publication. Dr. Glasgow is now with the
National Cancer Institute (NCI). This article does not necessarily
reflect the opinions of the CDC or the NCI. We are grateful for the
participation of the six county health departments in North Carolina
that participated in the study: Davidson, Forsyth, Lincoln, Nash,
Pasquotank, and Warren.
NR 41
TC 5
Z9 5
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1930-7381
EI 1930-739X
J9 OBESITY
JI Obesity
PD SEP
PY 2013
VL 21
IS 9
BP 1764
EP 1773
DI 10.1002/oby.20317
PG 10
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 231ON
UT WOS:000325426600033
PM 23408464
ER
PT J
AU Nielsen, S
Sumner, AE
Miller, BV
Turkova, H
Klein, S
Jensen, MD
AF Nielsen, Soren
Sumner, Anne E.
Miller, Bernard V., III
Turkova, Hana
Klein, Samuel
Jensen, Michael D.
TI Free Fatty Acid Flux in African-American and Caucasian Adults-Effect of
Sex and Race
SO OBESITY
LA English
DT Article
ID SUBCUTANEOUS ADIPOSE-TISSUE; X-RAY ABSORPTIOMETRY; INSULIN-RESISTANCE;
WHITE WOMEN; BODY-FAT; ENERGY-EXPENDITURE; VISCERAL OBESITY; GLYCEROL
RELEASE; METABOLISM; GLUCOSE
AB Objective: Obesity, insulin resistance, and diabetes disproportionately affect African-American (AA) women. Abnormal adipose tissue free fatty acid (FFA) release is associated with these conditions. Resting energy expenditure (REE) and sex predict FFA release in Caucasians, but whether this is true in AA is unknown. The sex-specific relationships between FFA release, REE, and race was compared.
Design and Methods: 100 adults (47% AA, 50% male, age 32 +/- 8 years [mean +/- SD]) from three different centers underwent duplicate measures of FFA release ([U-C-13] palmitate) and REE (indirect calorimetry). Body composition was determined by DXA and abdominal imaging.
Results: AA participants had lower REE, but similar FFA concentrations and flux compared with Caucasian participants. The significant predictors of palmitate release were REE, sex, and race. REE and FFA flux were correlated in both sexes and both races. In a multiple linear regression analysis with palmitate flux as the dependent variable and REE, sex, race, total fat mass, fat-free mass, and insulin as independent variables, REE was the only independent predictor of FFA release in men. Both REE and race predicted palmitate flux in women.
Conclusions: FFA flux is related to REE, but the relationship differs in AA and Caucasian women.
C1 [Nielsen, Soren] Aarhus Univ Hosp, Dept Endocrinol & Internal Med, DK-8000 Aarhus, Denmark.
[Nielsen, Soren; Jensen, Michael D.] Mayo Clin, Endocrine Res Unit, Rochester, MN 55905 USA.
[Sumner, Anne E.; Miller, Bernard V., III] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MA USA.
[Miller, Bernard V., III; Klein, Samuel] Washington Univ, Sch Med, Ctr Human Nutr, St Louis, MO USA.
[Miller, Bernard V., III; Klein, Samuel] Washington Univ, Sch Med, Atkins Ctr Excellence Obes Med, St Louis, MO USA.
[Turkova, Hana] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
RP Jensen, MD (reprint author), Mayo Clin, Endocrine Res Unit, Rochester, MN 55905 USA.
EM jensen@mayo.edu
FU U.S. Public Health Service [K40484, DK50456, UL1 RR024150, DK 37948, DK
56341, UL1 RR024992]; Novo Nordic Foundation; Mayo Foundation; NIDDK;
NICHD
FX We acknowledge the technical assistance of the staff of the Mayo Clinic
GCRC. This work was supported by grants DK40484, DK50456, and UL1
RR024150 from the U.S. Public Health Service; by DK 37948, DK 56341, UL1
RR024992 (SK) from the U.S. Public Health Service; by grants from the
Novo Nordic Foundation (to SN), and by the Mayo Foundation. Anne E.
Sumner and Bernard V. Miller III were supported by the intramural
program of NIDDK. Hana Turkova was supported by the intramural program
of NICHD.
NR 28
TC 5
Z9 5
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1930-7381
EI 1930-739X
J9 OBESITY
JI Obesity
PD SEP
PY 2013
VL 21
IS 9
BP 1836
EP 1842
DI 10.1002/oby.20322
PG 7
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 231ON
UT WOS:000325426600043
PM 23418014
ER
PT J
AU Ebong, IA
Goff, DC
Rodriguez, CJ
Chen, HY
Bluemke, DA
Szklo, M
Bertoni, AG
AF Ebong, Imo A.
Goff, David C., Jr.
Rodriguez, Carlos J.
Chen, Haiying
Bluemke, David A.
Szklo, Moyses
Bertoni, Alain G.
TI The Relationship Between Measures of Obesity and Incident Heart Failure:
The Multi-Ethnic Study of Atherosclerosis
SO OBESITY
LA English
DT Article
ID LEFT-VENTRICULAR HYPERTROPHY; CORONARY-ARTERY CALCIUM; INDEPENDENT
RISK-FACTOR; BODY-MASS INDEX; CARDIOVASCULAR-DISEASE; WAIST
CIRCUMFERENCE; METABOLIC SYNDROME; PHYSICAL-ACTIVITY; ABDOMINAL OBESITY;
ASSOCIATION
AB Objective: To evaluate the strength of association of body mass index (BMI) and waist circumference (WC) with incident heart failure (HF), exploring our associations by ethnicity and age.
Design and Methods: 6,809 participants, aged 45-84 years old, without clinical cardiovascular disease (2000-2002), from the Multi-Ethnic Study of Atherosclerosis were included. Cox-Proportional hazards models were used to examine associations of BMI and WC with incident HF. The predictive abilities of BMI and WC were compared using receiver operating characteristic curves.
Results: Over a median follow-up of 7.6 years, there were 176 cases. BMI and WC were associated with incident HF in men (1.33 [1.10-1.61] and 1.38 [1.18-1.62], respectively] and women (1.70 [1.33-2.17] and 1.64 [1.29-2.08], respectively). These associations became non-significant after adjusting for obesity-related conditions (hypertension, dysglycemia, hypercholesterolemia, left ventricular hypertrophy, kidney disease, and inflammation). The associations of BMI and WC did not vary significantly by ethnicity or age-group, but were inverse in Hispanic men. The area under the curve for BMI and WC was 0.749 and 0.750, respectively, in men and 0.782 and 0.777, respectively, in women.
Conclusions: The association between obesity and incident HF is largely mediated by obesity-related conditions. BMI and WC have similar predictive abilities for incident HF.
C1 [Ebong, Imo A.] Univ So Calif, Dept Med, Los Angeles, CA USA.
[Goff, David C., Jr.] Colorado Sch Publ Hlth, Aurora, CO USA.
[Rodriguez, Carlos J.; Bertoni, Alain G.] Wake Forest Univ, Bowman Gray Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA.
[Rodriguez, Carlos J.; Bertoni, Alain G.] Wake Forest Univ, Bowman Gray Sch Med, Dept Med, Winston Salem, NC 27103 USA.
[Chen, Haiying] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
[Bluemke, David A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Szklo, Moyses] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
RP Ebong, IA (reprint author), Univ So Calif, Dept Med, Los Angeles, CA USA.
EM ebong@usc.edu
OI Bluemke, David/0000-0002-8323-8086
FU National Heart, Lung and Blood Institute (NHLBI) [N01-HC-95159,
N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164,
N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169];
NHLBI [5 T32 HL087730-03]
FX 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. The MESA study was supported by contracts
N01-HC-95159 through N01-HC-95169 from the National Heart, Lung and
Blood Institute (NHLBI). The T32 training grant was supported by grant 5
T32 HL087730-03 from the NHLBI. Imo Ebong proposed the study, analyzed
data and drafted the manuscript. David Goff, Carlos Rodriguez, and Alain
Bertoni contributed to study design and proposal development. Haiying
Chen analyzed data and supervised data analysis. Moyses Szklo and David
Bluemke contributed to manuscript writing and reviewed the draft for
intellectual content. All authors contributed to data interpretation,
revision of the manuscript draft, and approved the final version of the
manuscript.
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 1930-7381
EI 1930-739X
J9 OBESITY
JI Obesity
PD SEP
PY 2013
VL 21
IS 9
BP 1915
EP 1922
DI 10.1002/oby.20298
PG 8
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 231ON
UT WOS:000325426600053
PM 23441088
ER
PT J
AU Bray, M
Pomeroy, J
Knowler, WC
Bersamin, A
Hopkins, S
Brage, S
Stanhope, K
Havel, PJ
Boyer, BB
AF Bray, Maria
Pomeroy, Jeremy
Knowler, William C.
Bersamin, Andrea
Hopkins, Scarlett
Brage, Soren
Stanhope, Kimber
Havel, Peter J.
Boyer, Bert B.
TI Simple Anthropometrics Are More Correlated with Health Variables Than
Are Estimates of Body Composition in Yup'ik People
SO OBESITY
LA English
DT Article
ID CARDIOVASCULAR RISK-FACTORS; X-RAY ABSORPTIOMETRY; WAIST CIRCUMFERENCE;
METABOLIC SYNDROME; MASS INDEX; ADOLESCENTS; ADIPOSITY; BMI; FAT
AB Objectives: To (1) evaluate the relationships between several indices of obesity with obesity-related risk factors; (2) compare the accuracy of body composition estimates derived from anthropometry and bioimpedance analysis (BIA) to estimates of body composition assessed by doubly-labeled water (DLW); and (3) establish equations for estimating fat mass (FM), fat-free mass (FFM), and percent body fat (PBF) in Yup'ik people.
Design and Methods: Participants included 1,056 adult Yup'ik people from 11 communities in Southwestern Alaska. In a sub-study of 30 participants, we developed population-specific linear regression models for estimating FM, FFM, and PBF from anthropometrics, age, sex, and BIA against criterion measures derived from total body water assessed with DLW. These models were then used with the population cohort and we analyzed the relationships between obesity indices and several health-related and disease status variables: (1) fasting plasma lipids, (2) glucose, (3) HbA1c, (4) adiponectin, (5) blood pressure, (6) diabetes (DM), and (7) cerebrocoronary vascular disease (CCVD) which includes stroke and heart disease.
Results: The best model for estimating FM in the sub-study used only three variables-sex, waist circumference (WC), and hip circumference and had multiple R-2=0.9730. FFM and PBF were calculated from FM and body weight.
Conclusion: WC and other anthropometrics were more highly correlated with a number of obesity-elated risk factors than were direct estimates of body composition. Body composition in Yup'ik people can be accurately estimated from simple anthropometrics.
C1 [Bray, Maria; Knowler, William C.; Bersamin, Andrea; Hopkins, Scarlett; Boyer, Bert B.] Univ Alaska Fairbanks, Ctr Alaska Native Hlth Res, Fairbanks, AK 99775 USA.
[Pomeroy, Jeremy; Knowler, William C.] NIDDK, NIH, Phoenix, AZ USA.
[Brage, Soren] MRC, Epidemiol Unit, Cambridge, England.
[Stanhope, Kimber; Havel, Peter J.] Univ Calif Davis, Sch Vet Med, Dept Mol Biosci, Davis, CA 95616 USA.
[Stanhope, Kimber; Havel, Peter J.] Univ Calif Davis, Dept Nutr, Davis, CA 95616 USA.
RP Boyer, BB (reprint author), Univ Alaska Fairbanks, Ctr Alaska Native Hlth Res, Fairbanks, AK 99775 USA.
EM bboyer@alaska.edu
FU National Institutes of Health [R01DK074842, P20RR016430]; Intramural
Research Program of the National Institute of Diabetes; Digestive and
Kidney Diseases and funding to the University of Alaska President
FX This study was supported by Award Number R01DK074842 and P20RR016430
(Boyer). Dr. Peter Havel's laboratory receives support from National
Institutes of Health grants HL075675, HL091333, HL107256, AT003545, and
DK097307. This work was supported in part by the Intramural Research
Program of the National Institute of Diabetes and Digestive and Kidney
Diseases and funding to the University of Alaska President for
dedicating unrestricted funds from British Petroleum and ConocoPhillips.
NR 13
TC 1
Z9 1
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1930-7381
EI 1930-739X
J9 OBESITY
JI Obesity
PD SEP
PY 2013
VL 21
IS 9
BP E435
EP E438
DI 10.1002/oby.20125
PG 4
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 231ON
UT WOS:000325426600013
PM 23666898
ER
PT J
AU Pan, Q
Delahanty, LM
Jablonski, KA
Knowler, WC
Kahn, SE
Florez, JC
Franks, PW
AF Pan, Qing
Delahanty, Linda M.
Jablonski, Kathleen A.
Knowler, William C.
Kahn, Steven E.
Florez, Jose C.
Franks, Paul W.
CA Diabet Prevention Program Res Grp
TI Variation at the Melanocortin 4 Receptor Gene and Response to
Weight-Loss Interventions in the Diabetes Prevention Program
SO OBESITY
LA English
DT Article
ID LIFE-STYLE INTERVENTION; BODY-MASS INDEX; COMMON VARIANTS; PIMA-INDIANS;
MC4R GENE; BASE-LINE; OBESITY; METFORMIN; COHORT; RISK
AB Objective: To assess associations and genotype x treatment interactions for melanocortin 4 receptor (MC4R) locus variants and obesity-related traits.
Design and Methods: Diabetes prevention program (DPP) participants (N = 3,819, of whom 3,356 were genotyped for baseline and 3,234 for longitudinal analyses) were randomized into intensive lifestyle modification (diet, exercise, weight loss), metformin or placebo control. Adiposity was assessed in a subgroup (n = 909) using computed tomography. All analyses were adjusted for age, sex, ethnicity and treatment.
Results: The rs1943218 minor allele was nominally associated with short-term (6 month; P = 0.032) and long-term (2 year; P = 0.038) weight change. Eight SNPs modified response to treatment on short-term (rs17066856, rs9966412, rs17066859, rs8091237, rs17066866, rs7240064) or long-term (rs12970134, rs17066866) reduction in body weight, or diabetes incidence (rs17066829) (all P-interaction < 0.05).
Conclusion: This is the first study to comprehensively assess the role of MC4R variants and weight regulation in a weight loss intervention trial. One MC4R variant was directly associated with obesity-related traits or diabetes; numerous other variants appear to influence body weight and diabetes risk by modifying the protective effects of the DPP interventions.
C1 [Pan, Qing; Jablonski, Kathleen A.] George Washington Univ, Biostat Ctr, Dept Biostat & Epidemiol, Dept Stat, Rockville, MD USA.
[Delahanty, Linda M.] Massachusetts Gen Hosp, Diabet Res Ctr, MGH Diabet Ctr, Dept Med, Boston, MA 02114 USA.
[Delahanty, Linda M.; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Knowler, William C.] NIDDK, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA.
[Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA USA.
[Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA.
[Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Franks, Paul W.] Lund Univ, Dept Clin Sci, Malmo, Sweden.
[Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Franks, Paul W.] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
RP Franks, PW (reprint author), Lund Univ, Dept Clin Sci, Malmo, Sweden.
EM paul.franks@med.lu.se
OI Franks, Paul/0000-0002-0520-7604; Kahn, Steven/0000-0001-7307-9002
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
of the National Institutes of Health; NIDDK; Indian Health Service;
Office of Research on Minority Health; National Institute of Child
Health and Human Development; National Institute on Aging; Centers for
Disease Control and Prevention; Office of Research on Women's Health;
Department of Veterans Affairs; American Diabetes Association; McKesson
BioServices Corp.; Matthews Media Group, Inc.; Henry M. Jackson
Foundation; Novo Nordisk; Swedish Research Council; Swedish Heart-Lung
Foundation; Swedish Diabetes Association; [R01 DK072041-02]
FX The National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK) of the National Institutes of Health provided funding to the
clinical centers and the Coordinating Center for the design and conduct
of the study; collection, management, analysis, and interpretation of
the data (U01 DK048489). The Southwestern American Indian Centers were
supported directly by the NIDDK and the Indian Health Service. The
General Clinical Research Center Program, National Center for Research
Resources supported data collection at many of the clinical centers.
Funding for data collection and participant support was also provided by
the Office of Research on Minority Health, the National Institute of
Child Health and Human Development, the National Institute on Aging, the
Centers for Disease Control and Prevention, the Office of Research on
Women's Health, the Department of Veterans Affairs, and the American
Diabetes Association. This research was also supported, in part, by the
intramural research program of the NIDDK. McKesson BioServices Corp.,
Matthews Media Group, Inc., and the Henry M. Jackson Foundation provided
support services under subcontract with the Coordinating Center. This
work was funded by R01 DK072041-02 to JCF and KAJ (PWF and WCK are
unpaid co-investigators). PWF was supported by grants from Novo Nordisk,
the Swedish Research Council, the Swedish Heart-Lung Foundation and the
Swedish Diabetes Association. SEK is supported in part by the Department
of Veterans Affairs. JCF has received consulting honoraria from
Novartis, Lilly and Pfizer. No other potential conflict of interest is
declared by any author.
NR 28
TC 11
Z9 11
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1930-7381
EI 1930-739X
J9 OBESITY
JI Obesity
PD SEP
PY 2013
VL 21
IS 9
BP E520
EP E526
DI 10.1002/oby.20459
PG 7
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 231ON
UT WOS:000325426600026
PM 23512951
ER
PT J
AU Koonin, EV
AF Koonin, Eugene V.
TI Genome as a stochastic evolutionary machine Comment on "How life changes
itself: The Read-Write (RW) genome" by James Shapiro
SO PHYSICS OF LIFE REVIEWS
LA English
DT Editorial Material
ID ELEMENTS; SYSTEM; PHAGE
C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM koonin@ncbi.nlm.nih.gov
FU Intramural NIH HHS
NR 18
TC 1
Z9 1
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1571-0645
EI 1873-1457
J9 PHYS LIFE REV
JI Phys. Life Rev.
PD SEP
PY 2013
VL 10
IS 3
BP 341
EP 343
DI 10.1016/j.plrev.2013.07.017
PG 3
WC Biology; Biophysics
SC Life Sciences & Biomedicine - Other Topics; Biophysics
GA 231UW
UT WOS:000325444900018
PM 23933228
ER
PT J
AU Lugassy, C
Peault, B
Wadehra, M
Kleinman, HK
Barnhill, RL
AF Lugassy, Claire
Peault, Bruno
Wadehra, Madhuri
Kleinman, Hynda K.
Barnhill, Raymond L.
TI Could pericytic mimicry represent another type of melanoma cell
plasticity with embryonic properties?
SO PIGMENT CELL & MELANOMA RESEARCH
LA English
DT Article
ID EXON-15 BRAF MUTATIONS; CUTANEOUS MELANOMA; NRAS MUTATIONS; SUBTYPES;
FREQUENCIES; UNCOMMON; SITES
AB We hypothesize that the interaction between angiotropic melanoma cells and the abluminal vascular surface can induce or sustain embryonic and/or stem cell migratory properties in these tumor cells. As a result, such angiotropic melanoma cells may migrate along the abluminal vascular surface, demonstrating pericytic mimicry. Through these cellular interactions, melanoma cells may migrate toward secondary sites.
C1 [Lugassy, Claire; Wadehra, Madhuri; Barnhill, Raymond L.] Univ Calif Los Angeles, Med Ctr, Jonsson Comprehens Canc Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90024 USA.
[Peault, Bruno] Univ Edinburgh, Queens Med Res Inst, Ctr Cardiovasc Sci, Edinburgh, Midlothian, Scotland.
[Peault, Bruno] Univ Calif Los Angeles, Med Ctr, Orthopaed Hosp Res Ctr, Los Angeles, CA 90024 USA.
[Kleinman, Hynda K.] NIDCR, NIH, Bethesda, MD USA.
RP Barnhill, RL (reprint author), Univ Calif Los Angeles, Med Ctr, Jonsson Comprehens Canc Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90024 USA.
EM RBarnhill@mednet.ucla.edu
FU Medical Research Council [G1000816]
NR 11
TC 11
Z9 11
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-1471
EI 1755-148X
J9 PIGM CELL MELANOMA R
JI Pigment Cell Melanoma Res.
PD SEP
PY 2013
VL 26
IS 5
BP 746
EP 754
DI 10.1111/pcmr.12120
PG 9
WC Oncology; Cell Biology; Dermatology
SC Oncology; Cell Biology; Dermatology
GA 204TG
UT WOS:000323391700021
PM 23789776
ER
PT J
AU Stokes, W
Srinivas, G
McFarland, R
Kulpa-Eddy, J
Casey, W
Walker, A
Draayer, H
Sebring, R
Brown, K
Balks, E
Stirling, C
Klaasen, E
Hill, R
Rippke, B
Ruby, K
Alt, D
Mukhopadhyay, S
Kojima, H
Johnson, N
Rinckel, L
Doelling, V
Jones, B
AF Stokes, William
Srinivas, Geetha
McFarland, Richard
Kulpa-Eddy, Jodie
Casey, Warren
Walker, Angela
Draayer, Hans
Sebring, Randy
Brown, Karen
Balks, Elisabeth
Stirling, Catrina
Klaasen, Eric
Hill, Richard
Rippke, Byron
Ruby, Kevin
Alt, David
Mukhopadhyay, Suman
Kojima, Hajime
Johnson, Nelson
Rinckel, Lori
Doelling, Vivian
Jones, Brett
TI Report on the international workshop on alternative methods for
Leptospira vaccine potency testing: State of the science and the way
forward
SO BIOLOGICALS
LA English
DT Article
DE Leptospira vaccines; Alternative methods; Potency; Replacement;
Refinement; Reduction
ID RELATIVE POTENCY; LETHAL INFECTION; DISEASE; ASSAY; BUPRENORPHINE;
INTERROGANS; BACTERINS; PATHOGEN; POMONA
AB Routine potency testing of Leptospira vaccines is mostly conducted using a vaccination challenge test that involves large numbers of hamsters and unrelieved pain and distress. NICEATM, ICCVAM, and their international partners organized a workshop to review the state of the science of alternative methods that might replace, reduce, and refine the use of animals for veterinary Leptospira vaccine potency testing and to identify ways to advance improved alternative methods. Vaccine manufacturers were encouraged to initiate or continue product-specific validation using in vitro enzyme-linked immunosorbent assays as replacements for potency testing of four common Leptospira serogroups. Participants discussed the potential for eliminating the back-titration procedure in the hamster challenge assay, which could reduce animal use by 50% for each individual potency test. Further animal reduction may also be possible by using cryopreserved Leptospira stock to replace continual passaging through hamsters. Serology assays were identified as a way to further reduce and refine animal use but should be considered only after attempting in vitro assays. Workshop participants encouraged consideration of analgesics and use of earlier humane endpoints when the hamster vaccination challenge potency assay is used. International harmonization of alternative potency methods was recommended to avoid duplicative potency testing to meet regionally different requirements.
C1 [Stokes, William; Casey, Warren] NIEHS, Natl Toxicol Program Interagcy Ctr Evaluat Altern, Div Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA.
[Srinivas, Geetha; Walker, Angela; Hill, Richard; Rippke, Byron; Ruby, Kevin] USDA, Ctr Vet Biol, Ames, IA 50010 USA.
[McFarland, Richard] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA.
[Kulpa-Eddy, Jodie] USDA, Anim & Plant Hlth Inspect Serv, Riverdale, MD 20737 USA.
[Draayer, Hans] Gourdneck View Consulting LLC, Portage, MI 49002 USA.
[Sebring, Randy] Colorado Serum Co, Denver, CO 80216 USA.
[Brown, Karen] Pair ODocs Consultants, Parkville, MO 64152 USA.
[Balks, Elisabeth] Paul Ehrlich Inst, D-63225 Langen, Germany.
[Stirling, Catrina] Pfizer Ltd, Sandwich CT13 9NJ, Kent, England.
[Klaasen, Eric] MSD Anim Hlth, NL-5830 AA Boxmeer, Netherlands.
[Alt, David] USDA ARS, Ames, IA 50010 USA.
[Mukhopadhyay, Suman] NIAID, Bethesda, MD 20892 USA.
[Kojima, Hajime] Natl Inst Hlth Sci, Japanese Ctr Validat Alternat Methods, Setagaya Ku, Tokyo 1585801, Japan.
[Johnson, Nelson; Rinckel, Lori; Doelling, Vivian; Jones, Brett] Integrated Lab Syst Inc, Morrisville, NC 27560 USA.
RP Casey, W (reprint author), NIEHS, Natl Toxicol Program Interagcy Ctr Evaluat Altern, Div Natl Toxicol Program, NIH, POB 12233,MD K2-16, Res Triangle Pk, NC 27709 USA.
EM warren.casey@nih.gov
FU NICEATM; ICCVAM; EURL ECVAM; JaCVAM
FX The authors extend their sincere appreciation to all participants in the
international workshop for their contributions leading to the workshop
conclusions and recommendations. The members of the Leptospira Workshop
Organizing Committee, ICCVAM Interagency Biologics Working Group, and
NICEATM staff are acknowledged for their contributions to the planning
of the workshop, and all the invited experts are acknowledged for their
presentations and contributions to breakout group discussions and
workshop proceedings. Participating national/international validation
organizations from the International Cooperation on Alternative Test
Methods, including NICEATM, ICCVAM, EURL ECVAM, and JaCVAM, are also
gratefully acknowledged for their scientific contributions and financial
support. Finally, the authors gratefully acknowledge Dr. Raymond Tice
and Dr. John Bucher from the National Institute of Environmental Health
Sciences, National Institutes of Health, USA for their review of the
manuscript.
NR 62
TC 0
Z9 0
U1 0
U2 7
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1045-1056
J9 BIOLOGICALS
JI Biologicals
PD SEP
PY 2013
VL 41
IS 5
SI SI
BP 279
EP 294
DI 10.1016/j.biologicals.2013.06.013
PG 16
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Pharmacology & Pharmacy
GA 231VU
UT WOS:000325447300001
PM 23890729
ER
PT J
AU Qin, L
Smith, BD
Tsai, HL
Yaghi, NK
Neela, PH
Moake, M
Fu, J
Kasamon, YL
Prince, GT
Goswami, M
Rosner, GL
Levitsky, HI
Hourigan, CS
AF Qin, L.
Smith, B. D.
Tsai, H-L
Yaghi, N. K.
Neela, P. H.
Moake, M.
Fu, J.
Kasamon, Y. L.
Prince, G. T.
Goswami, M.
Rosner, G. L.
Levitsky, H. I.
Hourigan, C. S.
TI Induction of high-titer IgG antibodies against multiple
leukemia-associated antigens in CML patients with clinical responses to
K562/GVAX immunotherapy
SO BLOOD CANCER JOURNAL
LA English
DT Article
DE leukemia; chronic myeloid; cancer vaccines; immunotherapy; K562 cells
ID CHRONIC MYELOID-LEUKEMIA; BONE-MARROW TRANSPLANTATION; CHRONIC
MYELOGENOUS LEUKEMIA; GRAFT-VERSUS-LEUKEMIA; DONOR LYMPHOCYTE INFUSION;
CD8(+) T-CELLS; CELLULAR IMMUNOTHERAPY; CANCER-IMMUNOTHERAPY; PEPTIDE
VACCINATION; IMMUNE-RESPONSES
AB The ability to target myeloid leukemia with immunotherapy would represent a significant therapeutic advance. We report here immunological analysis of clinical trials of primary and secondary vaccination with K562/GM-CSF immunotherapy in adult chronic phase chronic myeloid leukemia patients (CML-CP) with suboptimal responses to imatinib mesylate. Using serological analysis of recombinant cDNA expression libraries of K562 with autologous vaccinated patient serum, we have identified 12 novel chronic myeloid leukemia-associated antigens (LAAs). We show that clinical responses following K562/GM-CSF vaccination are associated with induction of high-titer antibody responses to multiple LAAs. We observe markedly discordant patterns of baseline and induced antibody responses in these identically vaccinated patients. No single antigen was recognized in all responses to vaccination. We demonstrate that an additional 'booster' vaccination series can be given safely to those with inadequate responses to initial vaccination, and is associated with more frequent induction of IgG responses to antigens overexpressed in K562 vaccine compared with primary CML-CP. Finally, those with induced immune responses to the same LAAs often shared HLA subtypes and patients with clinical responses following vaccination recognized a partially shared but non-identical spectrum of antigens; both findings have potentially significant implications for cancer vaccine immunotherapy.
C1 [Qin, L.; Smith, B. D.; Tsai, H-L; Yaghi, N. K.; Neela, P. H.; Moake, M.; Fu, J.; Kasamon, Y. L.; Prince, G. T.; Rosner, G. L.; Levitsky, H. I.; Hourigan, C. S.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA.
[Goswami, M.; Hourigan, C. S.] NHLBI, Myeloid Malignancies Sect, Hematol Branch, Bethesda, MD 20892 USA.
[Levitsky, H. I.] Roche Glycart AG, Schlieren, Switzerland.
RP Hourigan, CS (reprint author), NHLBI, Myeloid Malignancies Sect, Hematol Branch, Room 6C 103C,10 Ctr Dr, Bethesda, MD 20892 USA.
EM hourigan@nih.gov
RI Hourigan, Christopher/S-2476-2016
OI Hourigan, Christopher/0000-0002-6189-8067
FU National Institutes of Health [5R01CA142620, 5T32AI007247, P30CA006973];
Intramural Research Program of the NIH, National Heart, Lung and Blood
Institute; Samuel Smith Award for Leukemia Research
FX We wish to thank Jerry Radich (Seattle), Nancy Hensel and A John Barrett
(Bethesda) for the gift of CML samples and Mary S Leffell of the
Clinical Immunogenetics Laboratory at the Johns Hopkins University
School of Medicine for molecular HLA typing results. This research was
supported by the National Institutes of Health grants 5R01CA142620,
5T32AI007247, P30CA006973 and the Intramural Research Program of the
NIH, National Heart, Lung and Blood Institute. BDS and CSH were also
supported in part by the Samuel Smith Award for Leukemia Research.
NR 60
TC 9
Z9 9
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2044-5385
J9 BLOOD CANCER J
JI Blood Cancer J.
PD SEP
PY 2013
VL 3
AR UNSP e145
DI 10.1038/bcj.2013.44
PG 11
WC Oncology
SC Oncology
GA 229PW
UT WOS:000325280500006
PM 24013666
ER
PT J
AU Fann, DYW
Lee, SY
Manzanero, S
Tang, SC
Gelderblom, M
Chunduri, P
Bernreuther, C
Glatzel, M
Cheng, YL
Thundyil, J
Widiapradja, A
Lok, KZ
Foo, SL
Wang, YC
Li, YI
Drummond, GR
Basta, M
Magnus, T
Jo, DG
Mattson, MP
Sobey, CG
Arumugam, TV
AF Fann, D. Yang-Wei
Lee, S-Y
Manzanero, S.
Tang, S-C
Gelderblom, M.
Chunduri, P.
Bernreuther, C.
Glatzel, M.
Cheng, Y-L
Thundyil, J.
Widiapradja, A.
Lok, K-Z
Foo, S. L.
Wang, Y-C
Li, Y-I
Drummond, G. R.
Basta, M.
Magnus, T.
Jo, D-G
Mattson, M. P.
Sobey, C. G.
Arumugam, T. V.
TI Intravenous immunoglobulin suppresses NLRP1 and NLRP3
inflammasome-mediated neuronal death in ischemic stroke
SO CELL DEATH & DISEASE
LA English
DT Article
DE IVIg; ischemic stroke; inflammasome; cell death; caspase
ID GLYCATION END-PRODUCTS; ANTHRAX LETHAL TOXIN; SPINAL-CORD-INJURY;
CELL-DEATH; BRAIN-INJURY; CEREBRAL-ISCHEMIA; MOLECULAR PLATFORM;
ACTIVATION; MECHANISMS; INHIBITION
AB Multi-protein complexes called inflammasomes have recently been identified and shown to contribute to cell death in tissue injury. Intravenous immunoglobulin (IVIg) is an FDA-approved therapeutic modality used for various inflammatory diseases. The objective of this study is to investigate dynamic responses of the NLRP1 and NLRP3 inflammasomes in stroke and to determine whether the NLRP1 and NLRP3 inflammasomes can be targeted with IVIg for therapeutic intervention. Primary cortical neurons were subjected to glucose deprivation (GD), oxygen-glucose deprivation (OGD) or simulated ischemia-reperfusion (I/R). Ischemic stroke was induced in C57BL/6J mice by middle cerebral artery occlusion, followed by reperfusion. Neurological assessment was performed, brain tissue damage was quantified, and NLRP1 and NLRP3 inflammasome protein levels were evaluated. NLRP1 and NLRP3 inflammasome components were also analyzed in postmortem brain tissue samples from stroke patients. Ischemia-like conditions increased the levels of NLRP1 and NLRP3 inflammasome proteins, and IL-1 beta and IL-18, in primary cortical neurons. Similarly, levels of NLRP1 and NLRP3 inflammasome proteins, IL-1 beta and IL-18 were elevated in ipsilateral brain tissues of cerebral I/R mice and stroke patients. Caspase-1 inhibitor treatment protected cultured cortical neurons and brain cells in vivo in experimental stroke models. IVIg treatment protected neurons in experimental stroke models by a mechanism involving suppression of NLRP1 and NLRP3 inflammasome activity. Our findings provide evidence that the NLRP1 and NLRP3 inflammasomes have a major role in neuronal cell death and behavioral deficits in stroke. We also identified NLRP1 and NLRP3 inflammasome inhibition as a novel mechanism by which IVIg can protect brain cells against ischemic damage, suggesting a potential clinical benefit of therapeutic interventions that target inflammasome assembly and activity.
C1 [Fann, D. Yang-Wei; Lee, S-Y; Manzanero, S.; Chunduri, P.; Cheng, Y-L; Thundyil, J.; Widiapradja, A.; Lok, K-Z; Foo, S. L.; Arumugam, T. V.] Univ Queensland, Sch Biomed Sci, St Lucia, Qld, Australia.
[Tang, S-C; Wang, Y-C; Li, Y-I] Natl Taiwan Univ Hosp, Stroke Ctr, Dept Neurol, Taipei, Taiwan.
[Gelderblom, M.; Magnus, T.] Univ Clin Hamburg Eppendorf, Dept Neurol, Hamburg, Germany.
[Bernreuther, C.; Glatzel, M.] Univ Clin Hamburg Eppendorf, Inst Neuropathol, Hamburg, Germany.
[Drummond, G. R.; Sobey, C. G.] Monash Univ, Dept Pharmacol, Clayton, Vic 3168, Australia.
[Basta, M.] Biovisions Inc, Potomac, MD USA.
[Jo, D-G; Arumugam, T. V.] Sungkyunkwan Univ, Sch Pharm, Suwon, South Korea.
[Mattson, M. P.] NIA, Lab Neurosci, Intramural Res Program, Baltimore, MD 21224 USA.
[Arumugam, T. V.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Physiol, Singapore 117595, Singapore.
RP Arumugam, TV (reprint author), Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Physiol, MD9, Singapore 117595, Singapore.
EM chris.sobey@monash.edu; phstva@nus.edu.sg
RI Sobey, Christopher/A-2786-2008; Chunduri, Prasad/J-2141-2014; Glatzel,
Markus/G-3356-2011; Arumugam, Thiruma/B-4898-2011;
OI Glatzel, Markus/0000-0002-7720-8817; Tang,
Sung-Chun/0000-0003-3731-5973; Basta, Milan/0000-0001-5958-9241;
Drummond, Grant/0000-0001-8556-9738; Chunduri,
Prasad/0000-0001-7297-7580; LI, YU-I/0000-0002-9888-1541; Manzanero,
Silvia/0000-0002-5294-7082
FU The ARC Future Fellowship [FT100100427]; Academia Sinica, Biosignature
grant [BM102021169]; National Institute on Aging Intramural Research
Program
FX The ARC Future Fellowship (FT100100427) awarded to TVA, Academia Sinica,
Biosignature grant (BM102021169) to SCT and the National Institute on
Aging Intramural Research Program supported this work. CGS and GRD are
Senior Research Fellows of the National Health and Medical Research
Council of Australia.
NR 53
TC 70
Z9 72
U1 7
U2 31
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-4889
J9 CELL DEATH DIS
JI Cell Death Dis.
PD SEP
PY 2013
VL 4
AR e790
DI 10.1038/cddis.2013.326
PG 10
WC Cell Biology
SC Cell Biology
GA 230VC
UT WOS:000325370300007
PM 24008734
ER
PT J
AU Moss, B
AF Moss, Bernard
TI Poxvirus DNA Replication
SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
LA English
DT Article
ID VACCINIA VIRUS-DNA; TEMPERATURE-SENSITIVE MUTANTS; HOLLIDAY JUNCTION
RESOLVASES; THREONINE PROTEIN-KINASE; I3L GENE-PRODUCT; VIRAL-DNA;
CYTOPLASMIC FACTORIES; POLYMERASE GENE; INFECTED CELLS; A20R PROTEIN
AB Poxviruses are large, enveloped viruses that replicate in the cytoplasm and encode proteins for DNA replication and gene expression. Hairpin ends link the two strands of the linear, double-stranded DNA genome. Viral proteins involved in DNA synthesis include a 117-kDa polymerase, a helicase-primase, a uracil DNA glycosylase, a processivity factor, a single-stranded DNA-binding protein, a protein kinase, and a DNA ligase. A viral FEN1 family protein participates in double-strand break repair. The DNA is replicated as long concatemers that are resolved by a viral Holliday junction endonuclease.
C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
EM bmoss@nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX I thank George Katsafanas for help with the figures. The review was
written with the support of the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 109
TC 15
Z9 15
U1 3
U2 13
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1943-0264
J9 CSH PERSPECT BIOL
JI Cold Spring Harbor Perspect. Biol.
PD SEP
PY 2013
VL 5
IS 9
AR a010199
DI 10.1101/cshperspect.a010199
PG 12
WC Cell Biology
SC Cell Biology
GA 228EO
UT WOS:000325168700006
ER
PT J
AU Mueller, F
Stasevich, TJ
Mazza, D
McNally, JG
AF Mueller, Florian
Stasevich, Timothy J.
Mazza, Davide
McNally, James G.
TI Quantifying transcription factor kinetics: At work or at play?
SO CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY
LA English
DT Review
DE Competition-ChIP; kinetic modeling; live-cell imaging; non-specific
binding; specific binding; transcription; transcription factor dynamics
ID FLUORESCENCE CORRELATION SPECTROSCOPY; SINGLE-MOLECULE LEVEL;
PROTEIN-DNA INTERACTIONS; TATA-BINDING PROTEIN; LIVING CELLS;
GENE-EXPRESSION; IN-VIVO; GLUCOCORTICOID-RECEPTOR; ANOMALOUS DIFFUSION;
LIVE CELLS
AB Transcription factors (TFs) interact dynamically in vivo with chromatin binding sites. Here we summarize and compare the four different techniques that are currently used to measure these kinetics in live cells, namely fluorescence recovery after photobleaching (FRAP), fluorescence correlation spectroscopy (FCS), single molecule tracking (SMT) and competition ChIP (CC). We highlight the principles underlying each of these approaches as well as their advantages and disadvantages. A comparison of data from each of these techniques raises an important question: do measured transcription kinetics reflect biologically functional interactions at specific sites (i.e. working TFs) or do they reflect non-specific interactions (i.e. playing TFs)? To help resolve this dilemma we discuss five key unresolved biological questions related to the functionality of transient and prolonged binding events at both specific promoter response elements as well as non-specific sites. In support of functionality, we review data suggesting that TF residence times are tightly regulated, and that this regulation modulates transcriptional output at single genes. We argue that in addition to this site-specific regulatory role, TF residence times also determine the fraction of promoter targets occupied within a cell thereby impacting the functional status of cellular gene networks. Thus, TF residence times are key parameters that could influence transcription in multiple ways.
C1 [Mueller, Florian] Inst Pasteur, CNRS, Computat Imaging & Modeling Unit, Paris, France.
[Mueller, Florian] Ecole Normale Super, Inst Biol, F-75231 Paris, France.
[Stasevich, Timothy J.] Osaka Univ, Grad Sch Frontier Biosci, Osaka, Japan.
[Mazza, Davide] Univ Milan, Osped San Raffaele, Ist Sci, Ctr Imaging Sperimentale, I-20127 Milan, Italy.
[Mazza, Davide] Univ Vita Salute San Raffaele, Milan, Italy.
[McNally, James G.] NCI, Fluorescence Imaging Grp, NIH, Bethesda, MD 20892 USA.
RP McNally, JG (reprint author), NCI, Fluorescence Imaging Grp, NIH, Bethesda, MD 20892 USA.
EM mcnallyj@exchange.nih.gov
RI Mueller, Florian/C-9075-2012; Mazza, Davide/R-5340-2016
OI Mueller, Florian/0000-0002-9622-4396; Mazza, Davide/0000-0003-2776-4142
FU Fondation pour la Recherche Medicale en France (FRM); Japan Society for
the Promotion of Science (JSPS); Marie Curie international incoming
fellowship [GA: 27432]; National Institutes of Health, National Cancer
Institute, Center for Cancer Research
FX FM was supported by the Fondation pour la Recherche Medicale en France
(FRM). TS was supported by the Japan Society for the Promotion of
Science (JSPS). DM was supported by Marie Curie international incoming
fellowship (GA: 27432). JM was supported by the intramural program of
the National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 138
TC 27
Z9 27
U1 5
U2 44
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1040-9238
J9 CRIT REV BIOCHEM MOL
JI Crit. Rev. Biochem. Mol. Biol.
PD SEP-OCT
PY 2013
VL 48
IS 5
BP 492
EP 514
DI 10.3109/10409238.2013.833891
PG 23
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 229PY
UT WOS:000325280700006
PM 24025032
ER
PT J
AU Wang, MY
Wang, HJH
Lakatta, EG
AF Wang, Mingyi
Wang, Hejia H.
Lakatta, Edward G.
TI Milk Fat Globule Epidermal Growth Factor VIII Signaling in Arterial Wall
Remodeling
SO CURRENT VASCULAR PHARMACOLOGY
LA English
DT Article
DE Milk fat globule epidermal growth factor VIII; arterial remodeling;
intervention
ID SMOOTH-MUSCLE-CELLS; COMPARATIVE PROTEOMIC ANALYSIS; CIRCULATING
MICROPARTICLES; METABOLIC SYNDROME; ENDOTHELIAL-CELLS; ELDERLY-PATIENTS;
APOPTOTIC CELLS; FACTOR RECEPTOR; MAJOR PROTEINS; MOUSE MODEL
AB Arterial inflammation and remodeling, important sequellae of advancing age, are linked to the pathogenesis of age-associated arterial diseases e.g. hypertension, atherosclerosis, and metabolic disorders. Recently, high-throughput proteomic screening has identified milk fat globule epidermal growth factor VIII (MFG-E8) as a novel local biomarker for aging arterial walls. Additional studies have shown that MFG-E8 is also an element of the arterial inflammatory signaling network. The transcription, translation, and signaling levels of MFG-E8 are increased in aged, atherosclerotic, hypertensive, and diabetic arterial walls in vivo as well as activated vascular smooth muscle cells (VSMC) and a subset of macrophages in vitro. In VSMC, MFG-E8 increases proliferation and invasion as well as the secretion of inflammatory molecules. In endothelial cells (EC), MFG-E8 facilitates apoptosis. In addition, MFG-E8 has been found to be an essential component of the endothelial-derived microparticles that relay biosignals and modulate arterial wall phenotypes.
This review mainly focuses upon the landscape of MFG-E8 expression and signaling in adverse arterial remodeling. Recent discoveries have suggested that MFG-E8 associated interventions are novel approaches for the retardation of the enhanced rates of VSMC proliferation and EC apoptosis that accompany arterial wall inflammation and remodeling during aging and age-associated arterial disease.
C1 [Wang, Mingyi; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA.
[Wang, Hejia H.] Univ Penn, Sch Arts & Sci, Philadelphia, PA 19104 USA.
RP Wang, MY (reprint author), NIA, Cardiovasc Sci Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM mingyiw@grc.nia.nih.gov
FU National Institute on Aging, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute on Aging, National Institutes of Health.
NR 82
TC 7
Z9 9
U1 0
U2 9
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1570-1611
J9 CURR VASC PHARMACOL
JI Current Vascular Pharmacology
PD SEP
PY 2013
VL 11
IS 5
BP 768
EP 776
PG 9
WC Pharmacology & Pharmacy; Peripheral Vascular Disease
SC Pharmacology & Pharmacy; Cardiovascular System & Cardiology
GA 224EJ
UT WOS:000324865000014
PM 22272902
ER
PT J
AU Cupul-Uicab, LA
Klebanoff, MA
Brock, JW
Longnecker, MP
AF Cupul-Uicab, Lea A.
Klebanoff, Mark A.
Brock, John W.
Longnecker, Matthew P.
TI Prenatal Exposure to Persistent Organochlorines and Childhood Obesity in
the US Collaborative Perinatal Project
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
ID BODY-MASS INDEX; ENDOCRINE-DISRUPTING CHEMICALS;
POLYCHLORINATED-BIPHENYLS; CAUSAL-DIAGRAMS; IN-UTERO; GROWTH;
OVERWEIGHT; CHILDREN; BIRTH; RISK
AB Background: In some previous studies, prenatal exposure to persistent organochlorines such as 1,1,-dichloro-2,2-bis(p-chlorophenyl) ethylene (p,p' -DDE), polychlorinated biphenyls (PCBs), and hexachlorobenzene (HCB) has been associated with higher body mass index (BMI) in children.
Objective: Our goal was to evaluate the association of maternal serum levels of beta-hexachlorocyclohexane (beta-HCH), p,p' -DDE, dichlorodiphenyltrichloroethane (p,p' -DDT), dieldrin, heptachlor epoxide, HCB, trans-nonachlor, oxychlordane, and PCBs with offspring obesity during childhood.
Methods: The analysis was based on a subsample of 1,915 children followed until 7 years of age as part of the U.S. Collaborative Perinatal Project (CPP). The CPP enrolled pregnant women in 1959-1965; exposure levels were measured in third-trimester maternal serum that was collected before these organochlorines were banned in the United States. Childhood overweight and obesity were defined using age-and sex-specific cut points for BMI as recommended by the International Obesity Task Force.
Results: Adjusted results did not show clear evidence for an association between organochlorine exposure and obesity; however, a suggestive finding emerged for dieldrin. Compared with those in the lowest quintile (dieldrin, <0.57 mu g/L), odds of obesity were 3.6 (95% CI: 1.3, 10.5) for the fourth and 2.3 (95% CI: 0.8, 7.1) for the highest quintile. Overweight and BMI were unrelated to organochlorine exposure.
Conclusions: In this population with relatively high levels of exposure to organochlorines, no clear associations with obesity or BMI emerged.
C1 [Cupul-Uicab, Lea A.; Longnecker, Matthew P.] Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Epidemiol Branch, Res Triangle Pk, NC USA.
[Cupul-Uicab, Lea A.] Natl Inst Publ Hlth, Ctr Populat Hlth Res, Cuernavaca 62100, Morelos, Mexico.
[Klebanoff, Mark A.] Ohio State Univ, Coll Med, Columbus, OH 43210 USA.
[Klebanoff, Mark A.] Nationwide Childrens Hosp, Res Inst, Columbus, OH USA.
[Brock, John W.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA.
RP Cupul-Uicab, LA (reprint author), Natl Inst Publ Hlth, Ctr Populat Hlth Res, Ave Univ 655, Cuernavaca 62100, Morelos, Mexico.
EM lea.cupul@insp.mx
RI CUPUL UICAB, LEA/C-8699-2014;
OI CUPUL UICAB, LEA/0000-0001-6190-4474; Longnecker,
Matthew/0000-0001-6073-5322
FU National Institute of Environmental Health Sciences; National Institutes
of Health
FX This research was supported by the Intramural Research Program of the
National Institute of Environmental Health Sciences, National Institutes
of Health.
NR 41
TC 19
Z9 19
U1 1
U2 12
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD SEP
PY 2013
VL 121
IS 9
BP 1103
EP 1109
DI 10.1289/ehp.1205901
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 227XS
UT WOS:000325149600027
PM 23799652
ER
PT J
AU Schmidt, LS
AF Schmidt, Laura S.
TI Birt-Hogg-Dube syndrome: from gene discovery to molecularly targeted
therapies
SO FAMILIAL CANCER
LA English
DT Article
DE Birt-Hogg-Dube syndrome; BHD; FLCN; Folliculin; FNIP1; FNIP2; Tumor
suppressor; Inherited kidney cancer; Fibrofolliculoma
ID ACTIVATED PROTEIN-KINASE; RENAL TUMORS; BHD GENE; SPONTANEOUS
PNEUMOTHORAX; INTESTINAL POLYPOSIS; POLYCYSTIC KIDNEYS; SUPPRESSOR GENE;
MTOR ACTIVATION; CELL-LINE; FLCN
AB Since the hallmark dermatologic features of Birt-Hogg-Dub, (BHD) syndrome were first described by three Canadian physicians in 1977, the clinical manifestations of BHD have been expanded to include hamartomas of the hair follicle, lung cysts, increased risk for spontaneous pneumothorax and kidney neoplasia. Twenty-five years later the causative gene FLCN was identified, and the mutation spectrum has now been defined to include mainly protein truncating mutations, but also rare missense mutations and large gene deletions/duplication. Second "hit" FLCN mutations in BHD kidney tumors and loss of tumorigenic potential of the FLCN-null UOK257 tumor cell line when FLCN is re-expressed underscore a tumor suppressor role for FLCN. The identification of novel FLCN interacting proteins FNIP1 and FNIP2/L and their interaction with 5'-AMP activated protein kinase (AMPK) has provided a link between FLCN and the AMPK-mTOR axis and suggested molecular targets for therapeutic intervention to treat BHD kidney cancer and fibrofolliculomas. The generation of FLCN-null cell lines and in vivo animal models in which FLCN (or FNIP1) has been inactivated have provided critical reagents to facilitate mechanistic studies of FLCN function. Research efforts utilizing these critical FLCN-deficient cell lines and mice have begun to uncover important signaling pathways in which FLCN and its protein partners may play a role, including TGF-beta signaling, TFE3 transcriptional regulation, PGC1-alpha driven mitochondrial biogenesis, apoptotic response to cell stress, and vesicular transport. As the mechanisms by which FLCN inactivation leads to BHD manifestations are clarified, we can begin to develop therapeutic agents that target the pathways dysregulated in FLCN-deficient fibrofolliculomas and kidney tumors, providing improved prognosis and quality of life for BHD patients.
C1 [Schmidt, Laura S.] SAIC Frederick Inc, Basic Sci Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Schmidt, Laura S.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Schmidt, LS (reprint author), NCI, Urol Oncol Branch, NIH, Bldg 10 CRC Rm 1-3961,10 Ctr Dr MSC 1107, Bethesda, MD 20892 USA.
EM schmidtl@mail.nih.gov
FU NIH, Frederick National Lab, Center for Cancer Research; Frederick
National Laboratory for Cancer Research, National Institutes of Health
[HHSN261200800001E]
FX This research was supported in part by the Intramural Research Program
of the NIH, Frederick National Lab, Center for Cancer Research. This
project has been funded in part with Federal funds from the Frederick
National Laboratory for Cancer Research, National Institutes of Health,
under contract HHSN261200800001E. The content of this publication does
not necessarily reflect the views or policies of the Department of
Health and Human Services, not does mention of trade names, commercial
products or organizations imply endorsement by the U.S. Government.
NR 45
TC 16
Z9 16
U1 0
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1389-9600
J9 FAM CANCER
JI Fam. Cancer
PD SEP
PY 2013
VL 12
IS 3
SI SI
BP 357
EP 364
DI 10.1007/s10689-012-9574-y
PG 8
WC Oncology; Genetics & Heredity
SC Oncology; Genetics & Heredity
GA 231OJ
UT WOS:000325426200002
PM 23108783
ER
PT J
AU Stamatakis, L
Metwalli, AR
Middelton, LA
Linehan, WM
AF Stamatakis, Lambros
Metwalli, Adam R.
Middelton, Lindsay A.
Linehan, W. Marston
TI Diagnosis and management of BHD-associated kidney cancer
SO FAMILIAL CANCER
LA English
DT Article
DE Birt-Hogg-Dube; Clinical; Management; Syndrome; Kidney cancer; BHD;
Renal cell carcinoma
ID HOGG-DUBE-SYNDROME; RENAL TUMORS; SPONTANEOUS PNEUMOTHORAX; THERMAL
ABLATION; GENE; MUTATIONS; IDENTIFICATION; NEOPLASMS; FAMILIES; PROTEIN
AB In addition to the associated cutaneous and pulmonary manifestations, individuals with the Birt-Hogg-Dub, (BHD) syndrome have an increased risk of developing kidney cancer, which is often bilateral and multifocal. The risk of developing a renal tumor in this population does not decrease with age and therefore warrants a lifelong screening approach. We recommend abdominal imaging every 36 months in individuals without renal lesions at initial screening. Once renal tumors are identified, they should be followed with interval imaging studies until the largest tumor reaches 3 cm in maximal diameter, at which point nephron-sparing surgery should be ideally pursued. While the histology of renal tumors can vary in the BHD syndrome, most tumors possess a relatively indolent natural history and do not require adjuvant therapy if resected when localized to the kidney. With this approach, the vast majority of patients will achieve a curative oncologic outcome and avoid the medical sequelae of chronic renal insufficiency that could otherwise result from total nephrectomy.
C1 [Stamatakis, Lambros; Metwalli, Adam R.; Middelton, Lindsay A.; Linehan, W. Marston] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, 10 Ctr Dr MSC 1107,CRC Room 1W-5940, Bethesda, MD 20892 USA.
EM WML@nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research. The authors
wish to thank Georgia Shaw (editorial and graphics support), Dr. Maria
J. Merino (for providing the BHD kidney cancer histology images), and
Rabindra Gautam (for providing the radiologic images).
NR 22
TC 17
Z9 17
U1 0
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1389-9600
J9 FAM CANCER
JI Fam. Cancer
PD SEP
PY 2013
VL 12
IS 3
SI SI
BP 397
EP 402
DI 10.1007/s10689-013-9657-4
PG 6
WC Oncology; Genetics & Heredity
SC Oncology; Genetics & Heredity
GA 231OJ
UT WOS:000325426200007
PM 23703644
ER
PT J
AU Middelton, LA
AF Middelton, Lindsay A.
TI Birt-Hogg-Dube: beyond the clinical manifestations (vol 12, pg 97, 2013)
SO FAMILIAL CANCER
LA English
DT Correction
C1 NCI, NIH, Urol Oncol Branch, Bethesda, MD 20892 USA.
RP Middelton, LA (reprint author), NCI, NIH, Urol Oncol Branch, Bethesda, MD 20892 USA.
EM middeltl@mail.nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1389-9600
J9 FAM CANCER
JI Fam. Cancer
PD SEP
PY 2013
VL 12
IS 3
SI SI
BP 403
EP 403
DI 10.1007/s10689-013-9663-6
PG 1
WC Oncology; Genetics & Heredity
SC Oncology; Genetics & Heredity
GA 231OJ
UT WOS:000325426200008
ER
PT J
AU Thambisetty, M
Metter, J
Yang, A
Dolan, H
Marano, C
Zonderman, AB
Troncoso, JC
Zhou, Y
Wong, DF
Ferrucci, L
Egan, J
Resnick, SM
O'Brien, RJ
AF Thambisetty, Madhav
Metter, Jeffrey
Yang, An
Dolan, Hillary
Marano, Christopher
Zonderman, Alan B.
Troncoso, Juan C.
Zhou, Yun
Wong, Dean F.
Ferrucci, Luigi
Egan, Josephine
Resnick, Susan M.
O'Brien, Richard J.
TI Glucose Intolerance, Insulin Resistance, and Pathological Features of
Alzheimer Disease in the Baltimore Longitudinal Study of Aging
SO JAMA NEUROLOGY
LA English
DT Article
ID COGNITIVE DECLINE; DIABETES-MELLITUS; TOLERANCE TEST; RISK; DEMENTIA;
COMMUNITY; BRAIN; IMPAIRMENT; ROTTERDAM; HISAYAMA
AB IMPORTANCE Peripheral glucose homeostasis has been implicated in the pathogenesis of Alzheimer disease (AD). The relationship among diabetes mellitus, insulin, and AD is an important area of investigation. However, whether cognitive impairment seen in those with diabetes is mediated by excess pathological features of AD or other related abnormalities, such as vascular disease, remains unclear.
OBJECTIVE To investigate the association between serial measures of glucose intolerance and insulin resistance and in vivo brain beta-amyloid burden, measured with carbon 11-labeled Pittsburgh Compound B (11C-PiB), and AD pathology at autopsy.
DESIGN Scores calculated from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) and Braak criteria were correlated with measures of hyperglycemia, hyperinsulinemia, glucose intolerance, and insulin resistance in 197 participants who underwent autopsy after death and who had undergone 2 or more oral glucose tolerance tests (OGTT) using grouped analyses and a continuous mixed-models analysis. The same measures of glucose intolerance and insulin resistance were also correlated with brain 11C-PiB retention in an additional 53 living subjects from the Baltimore Longitudinal Study of Aging neuroimaging study.
SETTING Prospective, serially assessed cohort of community-dwelling subjects.
PARTICIPANTS Cohort 1 consisted of 197 participants enrolled in the Baltimore Longitudinal Study of Aging who had 2 or more OGTTs during life and a complete brain autopsy after death. Cohort 2 consisted of 53 living subjects who had 2 or more OGTTs and underwent brain 11C-PiB positron emission tomography.
EXPOSURES Autopsy and 11C-PiB positron emission tomography.
MAIN OUTCOMES AND MEASURES The correlation of brain markers of AD, including CERAD score, Braak score, and 11C-PiB retention, with serum markers of glucose homeostasis using grouped and continuous mixed-models analyses.
RESULTS We found no significant correlations between measures of brain AD pathology or 11C-PiB beta-amyloid load and glucose intolerance or insulin resistance in subjects who had a mean (SD) of 6.4 (3.2) OGTTs during 22.1 (8.0) years of follow-up. Thirty subjects with frank diabetes mellitus who received medications also had AD pathology scores that were similar to those of the cohort as a whole.
CONCLUSIONS AND RELEVANCE In this prospective cohort with multiple assessments of glucose intolerance and insulin resistance, measures of glucose and insulin homeostasis are not associated with AD pathology and likely play little role in AD pathogenesis. Long-term therapeutic trials are important to elucidate this issue.
C1 [Thambisetty, Madhav; Metter, Jeffrey; Yang, An; Zonderman, Alan B.; Ferrucci, Luigi; Egan, Josephine; Resnick, Susan M.] NIA, Res Program, Baltimore, MD 21224 USA.
[Dolan, Hillary; O'Brien, Richard J.] Johns Hopkins Bayview Med Ctr, Dept Neurol, Baltimore, MD 21224 USA.
[Marano, Christopher] Johns Hopkins Bayview Med Ctr, Dept Psychiat, Baltimore, MD 21224 USA.
[Troncoso, Juan C.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Zhou, Yun; Wong, Dean F.] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA.
RP O'Brien, RJ (reprint author), Johns Hopkins Bayview Med Ctr, Dept Neurol, Mason Lord Ctr Tower,Ste 5100, Baltimore, MD 21224 USA.
EM robrien@jhmi.edu
OI Zonderman, Alan B/0000-0002-6523-4778
FU National Institute on Aging (NIA) [P50 AG05146, U01 AG033655]; Burroughs
Wellcome Fund for Translational Research; Intramural Research Program,
NIA, National Institutes of Health
FX This study was supported by grants P50 AG05146 and U01 AG033655 from the
National Institute on Aging (NIA); by the Burroughs Wellcome Fund for
Translational Research; and by the Intramural Research Program, NIA,
National Institutes of Health.
NR 35
TC 44
Z9 45
U1 2
U2 17
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6149
J9 JAMA NEUROL
JI JAMA Neurol.
PD SEP
PY 2013
VL 70
IS 9
BP 1167
EP 1172
DI 10.1001/jamaneurol.2013.284
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 228TB
UT WOS:000325211600013
PM 23897112
ER
PT J
AU Chattaraj, P
Reimold, FR
Muskett, JA
Shmukler, BE
Chien, WW
Madeo, AC
Pryor, SP
Zalewski, CK
Butman, JA
Brewer, CC
Kenna, MA
Alper, SL
Griffith, AJ
AF Chattaraj, Parna
Reimold, Fabian R.
Muskett, Julie A.
Shmukler, Boris E.
Chien, Wade W.
Madeo, Anne C.
Pryor, Shannon P.
Zalewski, Christopher K.
Butman, John A.
Brewer, Carmen C.
Kenna, Margaret A.
Alper, Seth L.
Griffith, Andrew J.
TI Use of SLC26A4 Mutation Testing for Unilateral Enlargement of the
Vestibular Aqueduct
SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY
LA English
DT Article
ID GENOTYPE-PHENOTYPE CORRELATION; NONSYNDROMIC HEARING-LOSS;
PENDRED-SYNDROME; ALLELIC VARIANTS; GENE; DEAFNESS; DOMAIN; EVA; PDS
AB IMPORTANCE Approximately one-half of all subjects with unilateral or bilateral hearing loss with enlargement of the vestibular aqueduct (EVA) will have SLC26A4 gene mutations. The number (0, 1, or 2) of mutant alleles of SLC26A4 detected in an individual subject with EVA is each associated with a distinct combination of diagnostic and prognostic information as well as probability of recurrence of EVA in siblings.
OBJECTIVE To evaluate the results of SLC26A4 mutation testing in subjects with unilateral EVA. (The study objective was formulated before data were collected.)
DESIGN Prospective cross-sectional study of cohort ascertained between 1998 and 2012.
SETTING National Institutes of Health Clinical Center, a federal biomedical research facility.
PARTICIPANTS Twenty-four subjects (10 males, 14 females) with unilateral EVA, defined as a midpoint diameter greater than 1.5 mm, who were referred or self-referred to participate in a study about the clinical and molecular analysis of EVA. Twenty-one (87.5%) of 24 subjects were white. Mean age was 10.3 years (age range, 5-39 years).
INTERVENTION SLC26A4 mutation analysis.
MAIN OUTCOMES AND MEASURES Audiometric results, the presence or absence of EVA, and the number of mutant alleles of SLC26A4.
RESULTS Approximately 8.3% of the subjects with unilateral EVA had 2 mutant SLC26A4 alleles, 16.7% had 1 mutant allele, and 75.0% had 0 mutant alleles.
CONCLUSIONS AND RELEVANCE Unilateral EVA can be associated with all possible SLC26A4 genotype results. The distinct combination of prognoses and recurrence probability associated with each genotype supports the clinical use of testing for SLC26A4 mutations in subjects with unilateral EVA.
C1 [Chattaraj, Parna; Muskett, Julie A.; Madeo, Anne C.; Pryor, Shannon P.; Zalewski, Christopher K.; Brewer, Carmen C.; Griffith, Andrew J.] Natl Inst Deafness & Other Commun Disorders, Otolaryngol Branch, NIH, Rockville, MD 20850 USA.
[Reimold, Fabian R.; Shmukler, Boris E.; Alper, Seth L.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Renal, Boston, MA USA.
[Chien, Wade W.] Natl Inst Deafness & Other Commun Disorders, Off Clin Director, NIH, Bethesda, MD USA.
[Butman, John A.] NIH, Radiol & Imaging Sci Clin Ctr, Bethesda, MD 20892 USA.
[Kenna, Margaret A.] Boston Childrens Hosp, Dept Otolaryngol, Boston, MA USA.
[Kenna, Margaret A.] Boston Childrens Hosp, Dept Commun Enhancement, Boston, MA USA.
[Kenna, Margaret A.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
RP Griffith, AJ (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, 5 Res Ct,Room 2B28, Rockville, MD 20850 USA.
EM griffita@nidcd.nih.gov
RI Butman, John/J-2780-2013
OI Butman, John/0000-0002-1547-9195
FU National Institutes of Health [Z01-DC-000082, Z01-DC-000060,
Z01-DC-000064, R01 DK43495, R30 DK34854]; Robert Bosch Foundation
FX This study was supported by intramural research funds Z01-DC-000082 (Dr
Chien) and Z01-DC-000060 and Z01-DC-000064 (Dr Griffith), by grants R01
DK43495 and R30 DK34854 (The Harvard Digestive Diseases Center) (Dr
Alper) from the National Institutes of Health, and by the Robert Bosch
Foundation (Dr Reinmold).
NR 20
TC 7
Z9 7
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6181
J9 JAMA OTOLARYNGOL
JI JAMA Otolaryngol-Head Neck Surg.
PD SEP
PY 2013
VL 139
IS 9
BP 907
EP 913
DI 10.1001/jamaoto.2013.4185
PG 7
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 228IZ
UT WOS:000325180700005
PM 24051746
ER
PT J
AU Blasi, G
De Virgilio, C
Papazacharias, A
Taurisano, P
Gelao, B
Fazio, L
Ursini, G
Sinibaldi, L
Andriola, I
Masellis, R
Romano, R
Rampino, A
Di Giorgio, A
Lo Bianco, L
Caforio, G
Piva, F
Popolizio, T
Bellantuono, C
Todarello, O
Kleinman, JE
Gadaleta, G
Weinberger, DR
Bertolino, A
AF Blasi, Giuseppe
De Virgilio, Caterina
Papazacharias, Apostolos
Taurisano, Paolo
Gelao, Barbara
Fazio, Leonardo
Ursini, Gianluca
Sinibaldi, Lorenzo
Andriola, Ileana
Masellis, Rita
Romano, Raffaella
Rampino, Antonio
Di Giorgio, Annabella
Lo Bianco, Luciana
Caforio, Grazia
Piva, Francesco
Popolizio, Teresa
Bellantuono, Cesario
Todarello, Orlando
Kleinman, Joel E.
Gadaleta, Gemma
Weinberger, Daniel R.
Bertolino, Alessandro
TI Converging Evidence for the Association of Functional Genetic Variation
in the Serotonin Receptor 2a Gene With Prefrontal Function and
Olanzapine Treatment
SO JAMA PSYCHIATRY
LA English
DT Article
ID ATYPICAL ANTIPSYCHOTIC-DRUGS; WORKING-MEMORY PERFORMANCE; AMINO-ACID
SUBSTITUTIONS; 5-HT2A RECEPTOR; ATTENTIONAL CONTROL; CLINICAL-RESPONSE;
HIS452TYR POLYMORPHISM; PSYCHIATRIC-DISORDERS; COGNITIVE IMPAIRMENTS;
VAL(158)MET GENOTYPE
AB IMPORTANCE Serotonin (5-hydroxytryptamine) receptor 2a (5-HT2AR) signaling is important for modulation of corticostriatal pathways and prefrontal activity during cognition. Furthermore, newer antipsychotic drugs target 5-HT2AR. A single-nucleotide polymorphism in the 5-HT2AR gene (HTR2A rs6314, C>T; OMIM 182135) has been weakly associated with differential 5-HT2AR signaling and with physiologic as well as behavioral effects.
OBJECTIVE To use a hierarchical approach to determine the functional effects of this single-nucleotide polymorphism on 5-HT2AR messenger RNA and protein expression, on prefrontal phenotypes linked with genetic risk for schizophrenia, and on treatment with olanzapine.
DESIGN In silico predictions, in vitro, and case-control investigations.
SETTING Academic and clinical facilities.
PARTICIPANTS The postmortem study included 112 brains from healthy individuals; the in vivo investigation included a total sample of 371 healthy individuals and patients with schizophrenia.
EXPOSURES Patients received olanzapine monotherapy for 8 weeks.
MAIN OUTCOMES AND MEASURES In silico predictions, messenger RNA, and protein expression in postmortem human prefrontal cortex and HeLa cells, functional magnetic resonance imaging prefrontal activity and behavior during working memory and attention in healthy individuals, and response to an 8-week trial of olanzapine treatment in patients with schizophrenia.
RESULTS Bioinformatic analysis predicted that rs6314 alters patterns of splicing, with possible effects on HTR2A expression. Moreover, the T allele was associated with reduced prefrontal messenger RNA expression in postmortem prefrontal cortex, with reduced protein expression in vitro, inefficient prefrontal blood oxygen level-dependent functional magnetic resonance imaging response during working memory and attentional control processing, and impaired working memory and attention behavior, as well as with attenuated improvement in negative symptoms after olanzapine treatment.
CONCLUSIONS AND RELEVANCE Our results suggest that HTR2A rs6314 affects 5-HT2AR expression and functionally contributes to genetic modulation of known endophenotypes of schizophrenia-like higher-level cognitive behaviors and related prefrontal activity, as well as response to treatment with olanzapine.
C1 [Blasi, Giuseppe; Papazacharias, Apostolos; Taurisano, Paolo; Gelao, Barbara; Fazio, Leonardo; Ursini, Gianluca; Andriola, Ileana; Masellis, Rita; Romano, Raffaella; Rampino, Antonio; Lo Bianco, Luciana; Caforio, Grazia; Bertolino, Alessandro] Aldo Moro Univ, Grp Psychiat Neurosci, Dept Neurosci & Sense Organs, Bari, Italy.
[De Virgilio, Caterina; Gadaleta, Gemma] Aldo Moro Univ, Dept Biochem & Mol Biol Ernesto Quagliariello, Bari, Italy.
[Sinibaldi, Lorenzo; Di Giorgio, Annabella; Popolizio, Teresa] Ist Ricovero & Cura Carattere Sci Casa Sollievo, San Giovanni Rotondo, Italy.
[Lo Bianco, Luciana; Bellantuono, Cesario] Polytech Univ Marche, United Hosp Ancona, Psychiat Unit, Dept Mental Hlth, Ancona, Italy.
[Piva, Francesco] Polytech Univ Marche, Dept Biochem Biol & Genet, Ancona, Italy.
[Todarello, Orlando] Aldo Moro Univ, Dept Neurosci & Sense Organs, Bari, Italy.
[Kleinman, Joel E.] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA.
[Weinberger, Daniel R.] Lieber Inst Brain Dev, Baltimore, MD USA.
RP Bertolino, A (reprint author), Univ Bari Aldo Moro, Dipartimento Neurosci & Organi Senso, Piazza Giulio Cesare 9, I-70124 Bari, Italy.
EM alessandro.bertolino@uniba.it
RI Rampino, Antonio/Q-4465-2016; Di Giorgio, Annabella /D-7353-2017;
OI Rampino, Antonio/0000-0002-9654-3266; Di Giorgio, Annabella
/0000-0001-7876-3495; Papazacharias, Apostolos/0000-0001-5470-1601;
PIVA, Francesco/0000-0003-1850-2482
FU Brain and Behavior Research Foundation
FX This study was supported in part by a National Alliance for Research on
Schizophrenia and Depression (now Brain and Behavior Research
Foundation) Young Investigator Award to Dr Blasi.
NR 71
TC 18
Z9 19
U1 2
U2 6
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-622X
J9 JAMA PSYCHIAT
JI JAMA Psychiatry
PD SEP
PY 2013
VL 70
IS 9
BP 921
EP 930
DI 10.1001/jamapsychiatry.2013.1378
PG 10
WC Psychiatry
SC Psychiatry
GA 228JN
UT WOS:000325182200007
PM 23842608
ER
PT J
AU Seaquist, ER
Miller, ME
Fonseca, V
Ismail-Beigi, F
Launer, LJ
Punthakee, Z
Sood, A
AF Seaquist, Elizabeth R.
Miller, Michael E.
Fonseca, Vivian
Ismail-Beigi, Faramarz
Launer, Lenore J.
Punthakee, Zubin
Sood, Ajay
TI Effect of thiazolidinediones and insulin on cognitive outcomes in
ACCORD-MIND
SO JOURNAL OF DIABETES AND ITS COMPLICATIONS
LA English
DT Article
DE Thiazolidinediones; Insulin; Diabetes; Cognition
ID ROSIGLITAZONE; DISEASE; ASSOCIATION; IMPAIRMENT; MORTALITY; ADULTS; RISK
AB Objective: To examine the relationship of cognitive performance to exposure to insulin (INS) and thiazolidinediones (TZD) in the ACCORD-MIND cohort.
Methods: Participants (55-80 years) with type 2 diabetes (T2D), hemoglobin A1c (HbA1c) > 7.5% (> 58 mmol/mol), and a high risk of cardiovascular events were randomly assigned to receive intensive control targeting HbA1c to < 6.0% (42 mmol/mol) or a standard strategy targeting HbA1c to 7.0%-7.9% (53-63 mmol/mol). The Digit Symbol Substitution Test (DSST) was assessed at baseline and at 20 and 40 months. Exposure to INS was calculated as average daily dose/kg of body weight; exposure to rosiglitazone (ROS) was calculated as days of ROS prescription in the intervals preceding the 20- and 40-month DSSTs.
Results: At baseline, INS use was associated with reduced DSST performance, but not after controlling for comorbidities and lab values. There was no relationship between use of a TZID and DSST performance on at baseline. ROS but not INS exposure was associated with greater decline in DSST performance over 40 months in subjects randomized to the intensive but not the standard group.
Conclusions: Exposure to a TZD may increase cognitive decline in some patients with T2D. However, these results may be confounded by unexplained differences between participants. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Seaquist, Elizabeth R.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA.
[Miller, Michael E.] Wake Forest Univ, Div Publ Hlth Sci, Winston Salem, NC 27109 USA.
[Fonseca, Vivian] Tulane Univ, Dept Med, Endocrinol Sect, New Orleans, LA 70118 USA.
[Ismail-Beigi, Faramarz; Sood, Ajay] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Ismail-Beigi, Faramarz; Sood, Ajay] Cleveland VA Med Ctr, Cleveland, OH USA.
[Launer, Lenore J.] NIA, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Punthakee, Zubin] McMaster Univ, Dept Med, Hamilton, ON, Canada.
RP Seaquist, ER (reprint author), Univ Minnesota, Dept Med, Box 736 UMHC, Minneapolis, MN 55455 USA.
EM seaqu001@umn.edu
FU National Heart, Lung, and Blood Institute [N01-HC-95178, N01-HC-95179,
N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184,
IAA-Y1-HC-9035, IAA-Y1-HC-1010]; National Institutes of Health; National
Institute of Diabetes and Digestive and Kidney Diseases; National
Institute on Aging, and the National Eye Institute; Centers for Disease
Control and Prevention; General Clinical Research Centers
FX This work was supported by Grants (N01-HC-95178, N01-HC-95179,
N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184,
IAA-Y1-HC-9035, and IAA-Y1-HC-1010) from the National Heart, Lung, and
Blood Institute; by other components of the National Institutes of
Health, including the National Institute of Diabetes and Digestive and
Kidney Diseases, the National Institute on Aging, and the National Eye
Institute; by the Centers for Disease Control and Prevention; and by
General Clinical Research Centers. The following companies provided
study medications, equipment, or supplies: Abbott Laboratories, Amylin
Pharmaceutical, AstraZeneca, Bayer HealthCare, Closer Healthcare,
GlaxoSmithKline, King Pharmaceuticals, Merck, Novartis, Novo Nordisk,
Omron Healthcare, Sanofi-Aventis, and Schering-Plough.
NR 17
TC 12
Z9 12
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1056-8727
J9 J DIABETES COMPLICAT
JI J. Diabetes Complications
PD SEP-OCT
PY 2013
VL 27
IS 5
BP 485
EP 491
DI 10.1016/j.jdiacomp.2013.03.005
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 229WX
UT WOS:000325299700014
PM 23680059
ER
PT J
AU Hsu, C
Abad, JD
Morgan, RA
AF Hsu, Cary
Abad, John D.
Morgan, Richard A.
TI Characterization of human T lymphocytes engineered to express
interleukin-15 and herpes simplex virus-thymidine kinase
SO JOURNAL OF SURGICAL RESEARCH
LA English
DT Article
DE Human; T cells; Retroviral vector; Gene therapy; Cytokine; Cancer
immunotherapy; Suicide gene
ID CELL-TRANSFER THERAPY; METASTATIC MELANOMA; ADOPTIVE IMMUNOTHERAPY;
SUICIDE-GENE; IL-15 GENE; CANCER; CYTOKINE; LEUKEMIA; DISEASE; BIOLOGY
AB Introduction: Preclinical studies have demonstrated that tumor-reactive T cells expressing the interleukin (IL)-15 transgene had enhanced activity. Gene therapy strategies using IL-15 should include a safety mechanism in anticipation of possible adverse effects because IL-15 overexpression has been implicated in autoimmune disorders and may be involved in the pathogenesis of some leukemias. We developed a retroviral vector carrying both IL-15 and the herpes simplex virus-thymidine kinase (HSV-TK) suicide gene and characterized its application in the transduction of human T lymphocytes.
Methods: A retroviral vector carrying IL-15 and HSV-TK genes was optimized for the transduction of human T lymphocytes. IL-15 production was measured by enzyme-linked immunosorbent assay. Thymidine incorporation and cell viability assays were used to assess the efficacy of the HSV-TK suicide gene. Genetically modified tumor-infiltrating lymphocytes (TILs) were assayed for survival after withdrawal from exogenous IL-2. The activity and specificity of retrovirally transduced TILs were assessed using tumor coculture assays.
Results: Human T cells transduced with the IL-15 HSV-TK vector exhibited thymidine uptake in the absence of exogenous cytokine support and survived in culture for up to 80 d without IL-2. IL-15 HSV-TK-transduced T cells were efficiently killed by ganciclovir at concentrations as low as 0.1 mu M. TILs transduced with the IL-15 HSV-TK vector retained specific recognition of HLA-A2+, MART1+ melanomas, even after withdrawal of IL-2.
Conclusions: Human T lymphocytes genetically modified with the IL-15 HSV-TK retroviral vector retained the ability to recognize tumor antigen while gaining the ability to secrete IL-15 and prolong their own survival. IL-15 HSV-TK-transduced T cells expressed HSV-TK and could be efficiently eliminated by ganciclovir. Published by Elsevier Inc.
C1 [Hsu, Cary] Univ Calif Los Angeles, David Geffen Sch Med, Div Surg Oncol, Dept Gen Surg, Los Angeles, CA 90095 USA.
[Abad, John D.] Indiana Univ Hlth Goshen Ctr Canc Care, Dept Surg, Div Surg Oncol, Goshen, IN USA.
[Morgan, Richard A.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Hsu, C (reprint author), Univ Calif Los Angeles, Dept Gen Surg, Div Surg Oncol, David Geffen Sch Med, 1304 15th St,Suite 102, Santa Monica, CA 90404 USA.
EM caryhsu@mednet.ucla.edu
FU Intramural NIH HHS [Z99 CA999999]
NR 26
TC 2
Z9 3
U1 1
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0022-4804
J9 J SURG RES
JI J. Surg. Res.
PD SEP
PY 2013
VL 184
IS 1
BP 282
EP 289
DI 10.1016/j.jss.2013.03.054
PG 8
WC Surgery
SC Surgery
GA 207NX
UT WOS:000323609400047
PM 23582229
ER
PT J
AU Ouaguia, L
Morales, O
Senechal, M
Wychowski, C
Carpentier, A
Aoudjehane, L
Calmus, Y
de Launoit, Y
Conti, F
Delhem, N
AF Ouaguia, L.
Morales, O.
Senechal, M.
Wychowski, C.
Carpentier, A.
Aoudjehane, L.
Calmus, Y.
de Launoit, Y.
Conti, F.
Delhem, N.
TI In vitro infection with HCV increases the suppressive phenotype and
activity of the human regulatory T cell
SO JOURNAL OF VIRAL HEPATITIS
LA English
DT Meeting Abstract
CT Viral Hepatitis Congress
CY SEP 26-28, 2013
CL Frankfurt, GERMANY
C1 [Ouaguia, L.; Morales, O.; Senechal, M.; de Launoit, Y.; Delhem, N.] Inst Biol Lille, CNRS, UMR 8161, Lille, France.
[Wychowski, C.] Ctr Infect & Immun Lille, CNRS, INSERM, U1019,UMR8204, Lille, France.
[Carpentier, A.] NIH, Bethesda, MD 20892 USA.
[Aoudjehane, L.; Calmus, Y.; Conti, F.] Univ Paris 06, Paris, France.
[Aoudjehane, L.; Calmus, Y.; Conti, F.] CdR St Antoine, INSERM, UMR S 938, Paris, France.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1352-0504
J9 J VIRAL HEPATITIS
JI J. Viral Hepatitis
PD SEP
PY 2013
VL 20
SU 3
SI SI
BP 3
EP 3
PG 1
WC Gastroenterology & Hepatology; Infectious Diseases; Virology
SC Gastroenterology & Hepatology; Infectious Diseases; Virology
GA 225XI
UT WOS:000324998100006
ER
PT J
AU Yamaguchi, N
Driscoll, CA
Werdelin, L
Abramov, AV
Csorba, G
Cuisin, J
Fernholm, B
Hiermeier, M
Hills, D
Hunter, L
Itakura, H
Johansson, US
Kascheev, V
Krohmann, K
Martin, T
Nowak-Kemp, M
Pavlinov, IY
Renoud, F
Tomsett, L
van der Mije, S
Zholnerovskaya, E
Groves, C
Kitchener, AC
Nijman, V
Macdonald, DW
AF Yamaguchi, Nobuyuki
Driscoll, Carlos A.
Werdelin, Lars
Abramov, Alexei V.
Csorba, Gabor
Cuisin, Jacques
Fernholm, Bo
Hiermeier, Michael
Hills, Daphne
Hunter, Luke
Itakura, Hiroyuki
Johansson, Ulf S.
Kascheev, Vitaliy
Krohmann, Katrin
Martin, Thomas
Nowak-Kemp, Malgosia
Pavlinov, Igor Ya.
Renoud, Francis
Tomsett, Louise
van der Mije, Steven
Zholnerovskaya, Elena
Groves, Colin
Kitchener, Andrew C.
Nijman, Vincent
Macdonald, David W.
TI Locating specimens of extinct tiger (Panthera tigris) subspecies: Javan
tiger (P. t. sondaica), Balinese tiger (P. t. balica), and Caspian tiger
(P. t. virgata), including previously unpublished specimens
SO MAMMAL STUDY
LA English
DT Article
DE Central Asia; conservation; Indonesia; museum; Sunda Islands
ID PHYLOGEOGRAPHY; CONSERVATION; POPULATIONS; PHYLOGENY; SIZE; ASIA; LEO
AB Recent advances in multivariate statistics, and in ancient DNA techniques, have greatly increased understanding of tiger phylogeography. However, regardless of advances in analytical methodology, researchers will continue to need access to specimens for morphological measurements and sampling for genetic analysis. The tiger has become increasingly endangered, and out of the nine putative tiger subspecies, three (Javan, Balinese, and Caspian) have become extinct in the last 100 years, leaving the specimens kept in natural history collections as the only materials available for research. Frustratingly little information is widely available concerning the specimens of these extinct tiger subspecies. We conducted an extensive search for specimens of extinct tiger subspecies, and also developed a simple on-site method to assign unprovenanced and probable Indonesian specimens to either Javan/Balinese or Sumatran subspecies. We located a total of 88 Javan, 11 Balinese, and 46 Caspian tigers, including seven new Javan tigers, and three Balinese tigers that were not widely known previously. These specimens are critical for research in order to understand the intraspecific phylogeny and evolutionary history of the tiger.
C1 [Yamaguchi, Nobuyuki; Driscoll, Carlos A.; Macdonald, David W.] Univ Oxford, Dept Zool, Wildlife Conservat Res Unit, Recanati Kaplan Ctr, Abingdon OX13 5QL, Oxon, England.
[Driscoll, Carlos A.] NCI, Lab Genom Div, Frederick, MD 21702 USA.
[Werdelin, Lars; Fernholm, Bo; Johansson, Ulf S.] Swedish Museum Nat Hist, SE-10405 Stockholm, Sweden.
[Abramov, Alexei V.] Russian Acad Sci, Inst Zool, St Petersburg 199034, Russia.
[Csorba, Gabor] Hungarian Nat Hist Museum, H-1088 Budapest, Hungary.
[Cuisin, Jacques] Natl Museum Nat Hist, F-75005 Paris, France.
[Hiermeier, Michael; Renoud, Francis] Bavarian State Collect Zool, D-81247 Munich, Germany.
[Hills, Daphne; Tomsett, Louise] Nat Hist Museum, London SW7 5BD, England.
[Hunter, Luke] Wildlife Conservat Soc, Great Cats Program, Bronx, NY 10460 USA.
[Itakura, Hiroyuki] Cat Museum, Ito City, Shizuoka 4130235, Japan.
[Kascheev, Vitaliy] Inst Zool, Alma Ata 480060, Kazakhstan.
[Krohmann, Katrin; Martin, Thomas] Senckenberg Res Inst, D-60325 Frankfurt, Germany.
[Krohmann, Katrin; Martin, Thomas] Nat Hist Museum, D-60325 Frankfurt, Germany.
[Nowak-Kemp, Malgosia] Univ Oxford, Museum Nat Hist, Oxford OX1 3PW, England.
[Pavlinov, Igor Ya.] Moscow MV Lomonosov State Univ, Zool Museum, Moscow 125009, Russia.
[van der Mije, Steven] Netherlands Ctr Biodivers Naturalis, Natl Museum Nat Hist, NL-2300 RA Leiden, Netherlands.
[Zholnerovskaya, Elena] Russian Acad Sci, Siberian Zool Museum, Novosibirsk 630091, Russia.
[Groves, Colin] Australian Natl Univ, Sch Archaeol & Anthropol, Canberra, ACT 0200, Australia.
[Kitchener, Andrew C.] Natl Museums Scotland, Edinburgh EH1 1JF, Midlothian, Scotland.
[Kitchener, Andrew C.] Univ Edinburgh, Inst Geog, Sch Geosci, Edinburgh EH8 9XP, Midlothian, Scotland.
[Nijman, Vincent] Univ Amsterdam, Zool Museum, NL-1092 AD Amsterdam, Netherlands.
RP Yamaguchi, N (reprint author), Univ Qatar, Dept Biol & Environm Sci, POB 2713, Doha, Qatar.
EM yamaguchi@qu.edu.qa
RI Abramov, Alexei/A-9334-2011
OI Abramov, Alexei/0000-0001-9709-4469
FU Recanati-Kaplan Foundation
FX We thank the European Union SYNTHESYS programme for allowing NY to visit
the National Museum of Natural History, Paris, France, and the Museum of
Natural History, Berlin, Germany, to examine skulls, and British Airways
for transport between the UK and Kazakhstan, together with support of
DWM by the Recanati-Kaplan Foundation. We also thank Robert Asher,
Amankul Bekenov, Alex Borissenko, Peter Giere, Vitaliy Gromov, Olavi
Gronwall, Roman Jashenko, Paula Jenkins, Sergey Kruskop, Natasha
Lopatina, Doris Morike, Adri Rol, Richard Sabin, Chris Smeenk, Alexei
Tikhonov, Irene Thomas, Peter van Bree, Hein van Grouw, Detlef Willborn
for their kind support for locating specimens at their collections.
NR 30
TC 2
Z9 3
U1 2
U2 51
PU MAMMALOGICAL SOC JAPAN
PI KYOTO
PA C/O NAKANISHI PRINTING CO, LTD, KAMIGYO-KU, KYOTO, 602-8048, JAPAN
SN 1343-4152
EI 1348-6160
J9 MAMM STUDY
JI Mamm. Study
PD SEP
PY 2013
VL 38
IS 3
BP 187
EP 198
PG 12
WC Zoology
SC Zoology
GA 228MX
UT WOS:000325192000005
ER
PT J
AU Li, F
Jiang, CT
Krausz, KW
Li, YF
Albert, I
Hao, HP
Fabre, KM
Mitchell, JB
Patterson, AD
Gonzalez, FJ
AF Li, Fei
Jiang, Changtao
Krausz, Kristopher W.
Li, Yunfei
Albert, Istvan
Hao, Haiping
Fabre, Kristin M.
Mitchell, James B.
Patterson, Andrew D.
Gonzalez, Frank J.
TI Microbiome remodelling leads to inhibition of intestinal farnesoid X
receptor signalling and decreased obesity
SO NATURE COMMUNICATIONS
LA English
DT Article
ID BILE-ACID METABOLISM; GUT MICROBIOTA; INSULIN-RESISTANCE;
GLUCOSE-HOMEOSTASIS; MICE; METABOLOMICS; CERAMIDE; METAGENOMICS;
ACCUMULATION; CANCER
AB The antioxidant tempol reduces obesity in mice. Here we show that tempol alters the gut microbiome by preferentially reducing the genus Lactobacillus and its bile salt hydrolase (BSH) activity leading to the accumulation of intestinal tauro-beta-muricholic acid (T-beta-MCA). T-beta-MCA is an farnesoid X receptor (FXR) nuclear receptor antagonist, which is involved in the regulation of bile acid, lipid and glucose metabolism. Its increased levels during tempol treatment inhibit FXR signalling in the intestine. High-fat diet-fed intestine-specific Fxr-null (Fxr(Delta IE)) mice show lower diet-induced obesity, similar to tempol-treated wild-type mice. Further, tempol treatment does not decrease weight gain in Fxr(Delta IE) mice, suggesting that the intestinal FXR mediates the anti-obesity effects of tempol. These studies demonstrate a biochemical link between the microbiome, nuclear receptor signalling and metabolic disorders, and suggest that inhibition of FXR in the intestine could be a target for anti-obesity drugs.
C1 [Li, Fei; Jiang, Changtao; Krausz, Kristopher W.; Hao, Haiping; Patterson, Andrew D.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Li, Yunfei; Albert, Istvan] Penn State Univ, Bioinformat Consulting Ctr, University Pk, PA 16802 USA.
[Fabre, Kristin M.; Mitchell, James B.] NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Patterson, Andrew D.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
[Patterson, Andrew D.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA.
RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM gonzalef@mail.nih.gov
RI Li, Fei/F-6849-2013; Li, Yunfei/F-1546-2015; Patterson,
Andrew/G-3852-2012;
OI Patterson, Andrew/0000-0003-2073-0070; Hao, Haiping/0000-0003-2522-7546
FU Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health; Pennsylvania Department
of Health using Tobacco CURE Funds
FX We thank Grace L. Guo (Rutgers University) for providing the PGL4-Shp-TK
firefly luciferase construct and human FXR expression plasmid and Paul
A. Dawson (Wake Forest University School of Medicine) for providing the
human ASBT expression plasmid. This work was supported by the Intramural
Research Program of the Center for Cancer Research, National Cancer
Institute, National Institutes of Health. Sequencing was provided by the
Penn State Genomics Core Facility, University Park, PA. This project was
funded, in part, under a grant with the Pennsylvania Department of
Health using Tobacco CURE Funds.
NR 45
TC 108
Z9 113
U1 14
U2 79
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD SEP
PY 2013
VL 4
AR 2384
DI 10.1038/ncomms3384
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 232ZB
UT WOS:000325532400001
PM 24064762
ER
PT J
AU Carlson, CS
Matise, TC
North, KE
Haiman, CA
Fesinmeyer, MD
Buyske, S
Schumacher, FR
Peters, U
Franceschini, N
Ritchie, MD
Duggan, DJ
Spencer, KL
Dumitrescu, L
Eaton, CB
Thomas, F
Young, A
Carty, C
Heiss, G
Le Marchand, L
Crawford, DC
Hindorff, LA
Kooperberg, CL
AF Carlson, Christopher S.
Matise, Tara C.
North, Kari E.
Haiman, Christopher A.
Fesinmeyer, Megan D.
Buyske, Steven
Schumacher, Fredrick R.
Peters, Ulrike
Franceschini, Nora
Ritchie, Marylyn D.
Duggan, David J.
Spencer, Kylee L.
Dumitrescu, Logan
Eaton, Charles B.
Thomas, Fridtjof
Young, Alicia
Carty, Cara
Heiss, Gerardo
Le Marchand, Loic
Crawford, Dana C.
Hindorff, Lucia A.
Kooperberg, Charles L.
CA PAGE Consortium
TI Generalization and Dilution of Association Results from European GWAS in
Populations of Non-European Ancestry: The PAGE Study
SO PLOS BIOLOGY
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CORONARY-ARTERY-DISEASE; LINKAGE
DISEQUILIBRIUM; LOCI; REPLICATION; MUTATIONS; VARIANTS; CHINESE; TRAITS;
DESIGN
AB The vast majority of genome-wide association study (GWAS) findings reported to date are from populations with European Ancestry (EA), and it is not yet clear how broadly the genetic associations described will generalize to populations of diverse ancestry. The Population Architecture Using Genomics and Epidemiology (PAGE) study is a consortium of multi-ancestry, population-based studies formed with the objective of refining our understanding of the genetic architecture of common traits emerging from GWAS. In the present analysis of five common diseases and traits, including body mass index, type 2 diabetes, and lipid levels, we compare direction and magnitude of effects for GWAS-identified variants in multiple non-EA populations against EA findings. We demonstrate that, in all populations analyzed, a significant majority of GWAS-identified variants have allelic associations in the same direction as in EA, with none showing a statistically significant effect in the opposite direction, after adjustment for multiple testing. However, 25% of tagSNPs identified in EA GWAS have significantly different effect sizes in at least one non-EA population, and these differential effects were most frequent in African Americans where all differential effects were diluted toward the null. We demonstrate that differential LD between tagSNPs and functional variants within populations contributes significantly to dilute effect sizes in this population. Although most variants identified from GWAS in EA populations generalize to all non-EA populations assessed, genetic models derived from GWAS findings in EA may generate spurious results in non-EA populations due to differential effect sizes. Regardless of the origin of the differential effects, caution should be exercised in applying any genetic risk prediction model based on tagSNPs outside of the ancestry group in which it was derived. Models based directly on functional variation may generalize more robustly, but the identification of functional variants remains challenging.
C1 [Carlson, Christopher S.; Peters, Ulrike; Young, Alicia; Carty, Cara; Kooperberg, Charles L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Matise, Tara C.] Rutgers State Univ, Dept Genet, Piscataway, NJ USA.
[North, Kari E.; Franceschini, Nora; Heiss, Gerardo] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[North, Kari E.; Franceschini, Nora; Heiss, Gerardo] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA.
[Haiman, Christopher A.; Schumacher, Fredrick R.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Fesinmeyer, Megan D.] Seattle Childrens Res Inst, Ctr Child Hlth Behav & Dev, Seattle, WA USA.
[Buyske, Steven] Rutgers State Univ, Dept Stat & Biostat, Piscataway, NJ USA.
[Ritchie, Marylyn D.] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA.
[Duggan, David J.] Translat Genom Res Inst, Phoenix, AZ USA.
[Spencer, Kylee L.] Heidelberg Univ, Dept Biol & Environm Sci, Tiffin, OH USA.
[Dumitrescu, Logan; Crawford, Dana C.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Ctr Human Genet Res, Nashville, TN 37232 USA.
[Eaton, Charles B.] Brown Univ, Dept Family Med, Pawtucket, RI USA.
[Thomas, Fridtjof] Univ Tennessee, Ctr Hlth Sci, Div Biostat & Epidemiol, Dept Prevent Med,Coll Med, Memphis, TN 38163 USA.
[Le Marchand, Loic] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA.
[Hindorff, Lucia A.] NHGRI, Div Genom Med, NIH, Bethesda, MD 20892 USA.
RP Carlson, CS (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
EM ccarlson@fhcrc.org
RI Tiirikainen, Maarit/B-6954-2012; Nato, Alejandro/J-3880-2016;
OI Buyske, Steven/0000-0001-8539-5416; Tiirikainen,
Maarit/0000-0002-8124-3818; Nato, Alejandro/0000-0002-8745-9046; Bush,
William/0000-0002-9729-6519
FU National Human Genome Research Institute (NHGRI) [U01HG004798-01,
U01HG004802, U01HG004803]; NHLBI [N01-HV-48195, HHSN268201200036C,
N01-HC-85239, N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103,
N01 HC-55222, N01-HC-75150, N01-HC-45133]; Centers for Disease Control
and Prevention; National Cancer Institute [R37CA54281, R01 CA63,
P01CA33619, U01CA136792, U01CA98758]; NIH; US Department of Health and
Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13,
32115, 32118-32119, 32122, 42107-26, 42129-32, 44221]; National
Institutes of Health, National Heart, Lung and Blood Institute
[N01-HC-95095, N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050,
N01-HC-45134, N01-HC-05187, N01-HC-45205]; NIA [AG-023629, AG-15928,
AG-20098, AG-027058]; National Center for Research Resources
[M01-RR00425]; National Institute of Diabetes and Digestive and Kidney
Diseases [DK063491]; National Institutes of Mental Health; N.H.L.B.I
[HL080295, U01 HL65520, U01 HL41642, U01 HL41652, U01 HL41654, U01
HL65521, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019,
N01-HC-55020, N01-HC-55021, N01-HC-55022]
FX The Population Architecture Using Genomics and Epidemiology (PAGE)
program is funded by the National Human Genome Research Institute
(NHGRI). The data and materials included in this report result from a
collaboration between the following studies: The "Epidemiologic
Architecture for Genes Linked to Environment (EAGLE)'' is funded through
the NHGRI PAGE program (U01HG004798-01). Genotyping services for select
NHANES III SNPs presented here were also provided by the Johns Hopkins
University under federal contract number (N01-HV-48195) from NHLBI. The
study participants derive from the National Health and Nutrition
Examination Surveys (NHANES), and these studies are supported by the
Centers for Disease Control and Prevention. The findings and conclusions
in this report are those of the authors and do not necessarily represent
the views of the Centers for Disease Control and Prevention. The
Multiethnic Cohort study (MEC) characterization of epidemiological
architecture is funded through the NHGRI PAGE program (U01HG004802). The
MEC study is funded through the National Cancer Institute (R37CA54281,
R01 CA63, P01CA33619, U01CA136792, and U01CA98758). Funding support for
the "Epidemiology of putative genetic variants: The Women's Health
Initiative'' study is provided through the NHGRI PAGE program
(U01HG004790). The WHI program is funded by the National Heart, Lung,
and Blood Institute; NIH; and US Department of Health and Human Services
through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9,
32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221.
Funding support for the Genetic Epidemiology of Causal Variants Across
the Life Course (CALiCo) program was provided through the NHGRI PAGE
program (U01HG004803). The following studies contributed to this
manuscript and are funded by the following agencies: The Atherosclerosis
Risk in Communities (ARIC) Study is carried out as a collaborative study
supported by National Heart, Lung, and Blood Institute contracts
N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020,
N01-HC-55021, N01-HC-55022. The Coronary Artery Risk Development in
Young Adults (CARDIA) study is supported by the following National
Institutes of Health, National Heart, Lung and Blood Institute
contracts: N01-HC-95095; N01-HC-48047; N01-HC-48048; N01-HC-48049;
N01-HC-48050; N01-HC-45134; N01-HC-05187; and N01-HC-45205. The
Cardiovascular Health Study (CHS) is supported by NHLBI contracts
HHSN268201200036C, N01-HC-85239, N01-HC-85079 through N01-HC-85086;
N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133 and
NHLBI grant HL080295, with additional contribution from NINDS.
Additional support was provided through AG-023629, AG-15928, AG-20098,
and AG-027058 from the NIA. See also https://chs-nhlbi.org/. CHS GWAS
DNA handling and genotyping was supported in part by National Center for
Research Resources grant M01-RR00425 to the Cedars-Sinai General
Clinical Research Center Genotyping core and National Institute of
Diabetes and Digestive and Kidney Diseases grant DK063491 to the
Southern California Diabetes Endocrinology Research Center. The Strong
Heart Study (SHS) is supported by NHLBI grants U01 HL65520, U01 HL41642,
U01 HL41652, U01 HL41654, and U01 HL65521. The opinions expressed in
this paper are those of the author(s) and do not necessarily reflect the
views of the Indian Health Service.; Assistance with phenotype
harmonization, SNP selection and annotation, data cleaning, data
management, integration and dissemination, and general study
coordination was provided by the PAGE Coordinating Center
(U01HG004801-01). The National Institutes of Mental Health also
contributes to the support for the Coordinating Center. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 31
TC 40
Z9 40
U1 2
U2 16
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1545-7885
J9 PLOS BIOL
JI PLoS. Biol.
PD SEP
PY 2013
VL 11
IS 9
AR e1001661
DI 10.1371/journal.pbio.1001661
PG 11
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA 224SU
UT WOS:000324910500017
PM 24068893
ER
PT J
AU Candia, J
Maunu, R
Driscoll, M
Biancotto, A
Dagur, P
McCoy, JP
Sen, HN
Wei, L
Maritan, A
Cao, K
Nussenblatt, RB
Banavar, JR
Losert, W
AF Candia, Julian
Maunu, Ryan
Driscoll, Meghan
Biancotto, Angelique
Dagur, Pradeep
McCoy, J. Philip, Jr.
Sen, H. Nida
Wei, Lai
Maritan, Amos
Cao, Kan
Nussenblatt, Robert B.
Banavar, Jayanth R.
Losert, Wolfgang
TI From Cellular Characteristics to Disease Diagnosis: Uncovering
Phenotypes with Supercells
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID FLOW-CYTOMETRY DATA; GILFORD PROGERIA SYNDROME; CD4(+) T-CELLS;
SINGLE-CELL; HETEROGENEITY; EXPRESSION; IMMUNE
AB Cell heterogeneity and the inherent complexity due to the interplay of multiple molecular processes within the cell pose difficult challenges for current single-cell biology. We introduce an approach that identifies a disease phenotype from multiparameter single-cell measurements, which is based on the concept of `` supercell statistics'', a single-cell-based averaging procedure followed by a machine learning classification scheme. We are able to assess the optimal tradeoff between the number of single cells averaged and the number of measurements needed to capture phenotypic differences between healthy and diseased patients, as well as between different diseases that are difficult to diagnose otherwise. We apply our approach to two kinds of single-cell datasets, addressing the diagnosis of a premature aging disorder using images of cell nuclei, as well as the phenotypes of two non-infectious uveitides (the ocular manifestations of Behc, et's disease and sarcoidosis) based on multicolor flow cytometry. In the former case, one nuclear shape measurement taken over a group of 30 cells is sufficient to classify samples as healthy or diseased, in agreement with usual laboratory practice. In the latter, our method is able to identify a minimal set of 5 markers that accurately predict Behc, et's disease and sarcoidosis. This is the first time that a quantitative phenotypic distinction between these two diseases has been achieved. To obtain this clear phenotypic signature, about one hundred CD8(+) T cells need to be measured. Although the molecular markers identified have been reported to be important players in autoimmune disorders, this is the first report pointing out that CD8(+) T cells can be used to distinguish two systemic inflammatory diseases. Beyond these specific cases, the approach proposed here is applicable to datasets generated by other kinds of state-of-the-art and forthcoming single-cell technologies, such as multidimensional mass cytometry, single-cell gene expression, and single-cell full genome sequencing techniques.
C1 [Candia, Julian; Maunu, Ryan; Driscoll, Meghan; Banavar, Jayanth R.; Losert, Wolfgang] Univ Maryland, Dept Phys, College Pk, MD 20742 USA.
[Candia, Julian] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Candia, Julian] Univ La Plata, IFLYSIB, La Plata, Buenos Aires, Argentina.
[Candia, Julian] Univ La Plata, CONICET, La Plata, Buenos Aires, Argentina.
[Biancotto, Angelique; McCoy, J. Philip, Jr.] NIH, Ctr Human Immunol Autoimmun & Inflammat, Bethesda, MD 20892 USA.
[Biancotto, Angelique; Dagur, Pradeep; McCoy, J. Philip, Jr.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Sen, H. Nida; Wei, Lai; Nussenblatt, Robert B.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Maritan, Amos] Univ Padua, Dipartimento Fis G Galilei, Consorzio Nazl Interuniv Sci Fis Mat, Padua, Italy.
[Maritan, Amos] Ist Nazl Fis Nucl, Padua, Italy.
[Cao, Kan] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA.
RP Candia, J (reprint author), Univ Maryland, Dept Phys, College Pk, MD 20742 USA.
EM candia@umd.edu
RI Wei, Lai/D-1088-2014;
OI Candia, Julian/0000-0001-5793-8989
FU NIH [R00AG029761, R01GM085574, PHY1205965, 5T32CA154274-03]; CONICET
(Argentina)
FX KC was supported by NIH grant R00AG029761. WL and JC were partially
supported by NIH grants R01GM085574 and PHY1205965. JC was partially
supported by CONICET (Argentina) and NIH Project Number 5T32CA154274-03
(T32 Training Grant in Cancer Biology). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 38
TC 12
Z9 12
U1 2
U2 15
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD SEP
PY 2013
VL 9
IS 9
AR e1003215
DI 10.1371/journal.pcbi.1003215
PG 10
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA 227AZ
UT WOS:000325080900016
PM 24039568
ER
PT J
AU Bacolla, A
Temiz, NA
Yi, M
Ivanic, J
Cer, RZ
Donohue, DE
Ball, EV
Mudunuri, US
Wang, GL
Jain, A
Volfovsky, N
Luke, BT
Stephens, RM
Cooper, DN
Collins, JR
Vasquez, KM
AF Bacolla, Albino
Temiz, Nuri A.
Yi, Ming
Ivanic, Joseph
Cer, Regina Z.
Donohue, Duncan E.
Ball, Edward V.
Mudunuri, Uma S.
Wang, Guliang
Jain, Aklank
Volfovsky, Natalia
Luke, Brian T.
Stephens, Robert M.
Cooper, David N.
Collins, Jack R.
Vasquez, Karen M.
TI Guanine Holes Are Prominent Targets for Mutation in Cancer and Inherited
Disease
SO PLOS GENETICS
LA English
DT Article
ID SQUAMOUS-CELL CARCINOMA; ONE-ELECTRON OXIDATION; DEPENDENT DNA-DAMAGE;
B-FORM DNA; LUNG-CANCER; DENSITY FUNCTIONALS; NONCODING SEQUENCES;
SOMATIC MUTATION; BASE COMPOSITION; GGG TRIPLETS
AB Single base substitutions constitute the most frequent type of human gene mutation and are a leading cause of cancer and inherited disease. These alterations occur non-randomly in DNA, being strongly influenced by the local nucleotide sequence context. However, the molecular mechanisms underlying such sequence context-dependent mutagenesis are not fully understood. Using bioinformatics, computational and molecular modeling analyses, we have determined the frequencies of mutation at G.C bp in the context of all 64 5'-NGNN-3' motifs that contain the mutation at the second position. Twenty-four datasets were employed, comprising >530,000 somatic single base substitutions from 21 cancer genomes, >77,000 germline single-base substitutions causing or associated with human inherited disease and 16.7 million benign germline single-nucleotide variants. In several cancer types, the number of mutated motifs correlated both with the free energies of base stacking and the energies required for abstracting an electron from the target guanines ( ionization potentials). Similar correlations were also evident for the pathological missense and nonsense germline mutations, but only when the target guanines were located on the non-transcribed DNA strand. Likewise, pathogenic splicing mutations predominantly affected positions in which a purine was located on the non-transcribed DNA strand. Novel candidate driver mutations and tissue-specific mutational patterns were also identified in the cancer datasets. We conclude that electron transfer reactions within the DNA molecule contribute to sequence context-dependent mutagenesis, involving both somatic driver and passenger mutations in cancer, as well as germline alterations causing or associated with inherited disease.
C1 [Bacolla, Albino; Wang, Guliang; Jain, Aklank; Vasquez, Karen M.] Univ Texas Austin, Dell Pediat Res Inst, Div Pharmacol & Toxicol, Austin, TX 78712 USA.
[Bacolla, Albino; Temiz, Nuri A.; Yi, Ming; Ivanic, Joseph; Cer, Regina Z.; Donohue, Duncan E.; Mudunuri, Uma S.; Volfovsky, Natalia; Luke, Brian T.; Stephens, Robert M.; Collins, Jack R.] SAIC Frederic Inc, Frederick Natl Lab Canc Res, Adv Biomed Comp Ctr, Frederick, MD USA.
[Ball, Edward V.; Cooper, David N.] Cardiff Univ, Sch Med, Inst Med Genet, Cardiff CF10 3AX, S Glam, Wales.
RP Bacolla, A (reprint author), Univ Texas Austin, Dell Pediat Res Inst, Div Pharmacol & Toxicol, Austin, TX 78712 USA.
EM karen.vasquez@austin.utexas.edu
RI Bacolla, Albino/N-3877-2013;
OI Bacolla, Albino/0000-0003-0206-8423; Cooper, David
N./0000-0002-8943-8484
FU NIH [CA097175, CA093729]; NCI/NIH [HHSN261200800001E]; Frederick
National Laboratory for Cancer Research; CBIIT/caBIG ISRCE; BIOBASE
GmbH; Cardiff University
FX This work was supported by grants from the NIH (CA097175 and CA093729)
to KMV, NCI/NIH contract HHSN261200800001E to AB and the Frederick
National Laboratory for Cancer Research, and CBIIT/caBIG ISRCE yellow
task #09-260 to the Frederick National Laboratory for Cancer Research.
DNC and EVB received financial support from BIOBASE GmbH through a
license agreement (for HGMD) with Cardiff University. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 103
TC 11
Z9 11
U1 1
U2 18
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD SEP
PY 2013
VL 9
IS 9
AR e1003816
DI 10.1371/journal.pgen.1003816
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA 226ZM
UT WOS:000325076600071
PM 24086153
ER
PT J
AU Lada, AG
Stepchenkova, EI
Waisertreiger, ISR
Noskov, VN
Dhar, A
Eudy, JD
Boissy, RJ
Hirano, M
Rogozin, IB
Pavlov, YI
AF Lada, Artem G.
Stepchenkova, Elena I.
Waisertreiger, Irina S. R.
Noskov, Vladimir N.
Dhar, Alok
Eudy, James D.
Boissy, Robert J.
Hirano, Masayuki
Rogozin, Igor B.
Pavlov, Youri I.
TI Genome-Wide Mutation Avalanches Induced in Diploid Yeast Cells by a Base
Analog or an APOBEC Deaminase
SO PLOS GENETICS
LA English
DT Article
ID SACCHAROMYCES-CEREVISIAE GENOME; HUMAN CANCERS EXPRESS; DNA-REPLICATION;
ESCHERICHIA-COLI; ADAPTIVE MUTATION; MUTAGENIC SPECIFICITY; CYTOSINE
DEAMINATION; MISMATCH REPAIR; GENE; 6-N-HYDROXYLAMINOPURINE
AB Genetic information should be accurately transmitted from cell to cell; conversely, the adaptation in evolution and disease is fueled by mutations. In the case of cancer development, multiple genetic changes happen in somatic diploid cells. Most classic studies of the molecular mechanisms of mutagenesis have been performed in haploids. We demonstrate that the parameters of the mutation process are different in diploid cell populations. The genomes of drug-resistant mutants induced in yeast diploids by base analog 6-hydroxylaminopurine (HAP) or AID/APOBEC cytosine deaminase PmCDA1 from lamprey carried a stunning load of thousands of unselected mutations. Haploid mutants contained almost an order of magnitude fewer mutations. To explain this, we propose that the distribution of induced mutation rates in the cell population is uneven. The mutants in diploids with coincidental mutations in the two copies of the reporter gene arise from a fraction of cells that are transiently hypersensitive to the mutagenic action of a given mutagen. The progeny of such cells were never recovered in haploids due to the lethality caused by the inactivation of single-copy essential genes in cells with too many induced mutations. In diploid cells, the progeny of hypersensitive cells survived, but their genomes were saturated by heterozygous mutations. The reason for the hypermutability of cells could be transient faults of the mutation prevention pathways, like sanitization of nucleotide pools for HAP or an elevated expression of the PmCDA1 gene or the temporary inability of the destruction of the deaminase. The hypothesis on spikes of mutability may explain the sudden acquisition of multiple mutational changes during evolution and carcinogenesis.
C1 [Lada, Artem G.; Stepchenkova, Elena I.; Waisertreiger, Irina S. R.; Pavlov, Youri I.] Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA.
[Stepchenkova, Elena I.] Vavilov Inst Gen Genet, St Petersburg Branch, St Petersburg, Russia.
[Stepchenkova, Elena I.; Pavlov, Youri I.] St Petersburg Univ, Dept Genet, St Petersburg, Russia.
[Noskov, Vladimir N.] J Craig Venter Inst, Rockville, MD USA.
[Dhar, Alok; Eudy, James D.] Univ Nebraska, Med Ctr, Dept Genet Cell Biol & Anat, Omaha, NE USA.
[Dhar, Alok; Eudy, James D.] Univ Nebraska, Med Ctr, Munroe Meyer Inst, Omaha, NE USA.
[Boissy, Robert J.] Univ Nebraska, Med Ctr, Dept Internal Med, Omaha, NE USA.
[Hirano, Masayuki] Emory Univ, Emory Vaccine Ctr, Dept Pathol & Lab Med, Atlanta, GA USA.
[Rogozin, Igor B.] Natl Ctr Biotechnol Informat, NIH, Natl Lib Med, Bethesda, MD USA.
RP Lada, AG (reprint author), Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA.
EM ypavlov@unmc.edu
RI Stepchenkova, Elena/F-9931-2014
OI Stepchenkova, Elena/0000-0002-5854-8701
FU UNMC Eppley Cancer Center; NCI [CA129925]; Smoking Disease Research
Program DHHS grant [2013-21]; Russian Federal Government Research
Program "Innovative Scientific Personnel"; Federal Grant-in-Aid Program
"Human Capital for Science and Education in Innovative Russia" [8654];
Graduate Research Fellowship from the University of Nebraska Medical
Center; NIH [R01AI072435, R01GM100151]; Intramural Research Program of
the National Library of Medicine at the National Institutes of
Health/DHHS; NCRR [1S10RR027754-01, 5P20RR016469, RR018788-08]; National
Institute for General Medical Science (NIGMS) [8P20GM103427,
GM103471-09]; [14.740.11.0916]
FX The work was supported by UNMC Eppley Cancer Center seed grants and, in
part, by NCI grant CA129925; Smoking Disease Research Program DHHS grant
2013-21; by the Russian Federal Government Research Program "Innovative
Scientific Personnel"; State Contract 14.740.11.0916 to YIP; Federal
Grant-in-Aid Program "Human Capital for Science and Education in
Innovative Russia 2009-2013" to YIP; and the Federal Grant-in-Aid
Program "Human Capital for Science and Education in Innovative Russia"
(Governmental Contract No. 8654). AGL was supported by a Graduate
Research Fellowship from the University of Nebraska Medical Center. MH
was supported by NIH grants R01AI072435 and R01GM100151. IBR is
supported by the Intramural Research Program of the National Library of
Medicine at the National Institutes of Health/DHHS. The University of
Nebraska DNA Sequencing Core receives partial support from the NCRR
(1S10RR027754-01, 5P20RR016469, RR018788-08) and the National Institute
for General Medical Science (NIGMS) (8P20GM103427, GM103471-09). This
publication's contents are the sole responsibility of the authors and do
not necessarily represent the official views of the NIH, NCI or NIGMS.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 73
TC 20
Z9 20
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD SEP
PY 2013
VL 9
IS 9
AR e1003736
DI 10.1371/journal.pgen.1003736
PG 17
WC Genetics & Heredity
SC Genetics & Heredity
GA 226ZM
UT WOS:000325076600012
PM 24039593
ER
PT J
AU O'Seaghdha, CM
Wu, HS
Yang, Q
Kapur, K
Guessous, I
Zuber, AM
Kottgen, A
Stoudmann, C
Teumer, A
Kutalik, Z
Mangino, M
Dehghan, A
Zhang, WH
Eiriksdottir, G
Li, G
Tanaka, T
Portas, L
Lopez, LM
Hayward, C
Lohman, K
Matsuda, K
Padmanabhan, S
Firsov, D
Sorice, R
Ulivi, S
Brockhaus, AC
Kleber, ME
Mahajan, A
Ernst, FD
Gudnason, V
Launer, LJ
Mace, A
Boerwinckle, E
Arking, DE
Tanikawa, C
Nakamura, Y
Brown, MJ
Gaspoz, JM
Theler, JM
Siscovick, DS
Psaty, BM
Bergmann, S
Vollenweider, P
Vitart, V
Wright, AF
Zemunik, T
Boban, M
Kolcic, I
Navarro, P
Brown, EM
Estrada, K
Ding, JZ
Harris, TB
Bandinelli, S
Hernandez, D
Singleton, AB
Girotto, G
Ruggiero, D
d'Adamo, AP
Robino, A
Meitinger, T
Meisinger, C
Davies, G
Starr, JM
Chambers, JC
Boehm, BO
Winkelmann, BR
Huang, J
Murgia, F
Wild, SH
Campbell, H
Morris, AP
Franco, OH
Hofman, A
Uitterlinden, AG
Rivadeneira, F
Volker, U
Hannemann, A
Biffar, R
Hoffmann, W
Shin, SY
Lescuyer, P
Henry, H
Schurmann, C
Munroe, PB
Gasparini, P
Pirastu, N
Ciullo, M
Gieger, C
Marz, W
Lind, L
Spector, TD
Smith, AV
Rudan, I
Wilson, JF
Polasek, O
Deary, IJ
Pirastu, M
Ferrucci, L
Liu, YM
Kestenbaum, B
Kooner, JS
Witteman, JCM
Nauck, M
Kao, WHL
Wallaschofski, H
Bonny, O
Fox, CS
Bochud, M
AF O'Seaghdha, Conall M.
Wu, Hongsheng
Yang, Qiong
Kapur, Karen
Guessous, Idris
Zuber, Annie Mercier
Koettgen, Anna
Stoudmann, Candice
Teumer, Alexander
Kutalik, Zoltan
Mangino, Massimo
Dehghan, Abbas
Zhang, Weihua
Eiriksdottir, Gudny
Li, Guo
Tanaka, Toshiko
Portas, Laura
Lopez, Lorna M.
Hayward, Caroline
Lohman, Kurt
Matsuda, Koichi
Padmanabhan, Sandosh
Firsov, Dmitri
Sorice, Rossella
Ulivi, Sheila
Brockhaus, A. Catharina
Kleber, Marcus E.
Mahajan, Anubha
Ernst, Florian D.
Gudnason, Vilmundur
Launer, Lenore J.
Mace, Aurelien
Boerwinckle, Eric
Arking, Dan E.
Tanikawa, Chizu
Nakamura, Yusuke
Brown, Morris J.
Gaspoz, Jean-Michel
Theler, Jean-Marc
Siscovick, David S.
Psaty, Bruce M.
Bergmann, Sven
Vollenweider, Peter
Vitart, Veronique
Wright, Alan F.
Zemunik, Tatijana
Boban, Mladen
Kolcic, Ivana
Navarro, Pau
Brown, Edward M.
Estrada, Karol
Ding, Jingzhong
Harris, Tamara B.
Bandinelli, Stefania
Hernandez, Dena
Singleton, Andrew B.
Girotto, Giorgia
Ruggiero, Daniela
d'Adamo, Adamo Pio
Robino, Antonietta
Meitinger, Thomas
Meisinger, Christa
Davies, Gail
Starr, John M.
Chambers, John C.
Boehm, Bernhard O.
Winkelmann, Bernhard R.
Huang, Jie
Murgia, Federico
Wild, Sarah H.
Campbell, Harry
Morris, Andrew P.
Franco, Oscar H.
Hofman, Albert
Uitterlinden, Andre G.
Rivadeneira, Fernando
Voelker, Uwe
Hannemann, Anke
Biffar, Reiner
Hoffmann, Wolfgang
Shin, So-Youn
Lescuyer, Pierre
Henry, Hughes
Schurmann, Claudia
Munroe, Patricia B.
Gasparini, Paolo
Pirastu, Nicola
Ciullo, Marina
Gieger, Christian
Maerz, Winfried
Lind, Lars
Spector, Tim D.
Smith, Albert V.
Rudan, Igor
Wilson, James F.
Polasek, Ozren
Deary, Ian J.
Pirastu, Mario
Ferrucci, Luigi
Liu, Yongmei
Kestenbaum, Bryan
Kooner, Jaspal S.
Witteman, Jacqueline C. M.
Nauck, Matthias
Kao, W. H. Linda
Wallaschofski, Henri
Bonny, Olivier
Fox, Caroline S.
Bochud, Murielle
CA SUNLIGHT Consortium
GEFOS Consortium
TI Meta-Analysis of Genome-Wide Association Studies Identifies Six New Loci
for Serum Calcium Concentrations
SO PLOS GENETICS
LA English
DT Article
ID IMPRINTED PHLDA2 GENE; VITAMIN-D METABOLISM; PARATHYROID-HORMONE;
PHOSPHATE HOMEOSTASIS; PLACENTAL EXPRESSION; UROGENITAL SYSTEM;
RENAL-FUNCTION; MAMMARY-GLAND; BIRTH-WEIGHT; PLASMA
AB Calcium is vital to the normal functioning of multiple organ systems and its serum concentration is tightly regulated. Apart from CASR, the genes associated with serum calcium are largely unknown. We conducted a genome-wide association meta-analysis of 39,400 individuals from 17 population-based cohorts and investigated the 14 most strongly associated loci in <= 21,679 additional individuals. Seven loci (six new regions) in association with serum calcium were identified and replicated. Rs1570669 near CYP24A1 (P = 9.1E-12), rs10491003 upstream of GATA3 (P = 4.8E-09) and rs7481584 in CARS (P = 1.2E-10) implicate regions involved in Mendelian calcemic disorders: Rs1550532 in DGKD (P = 8.2E-11), also associated with bone density, and rs7336933 near DGKH/KIAA0564 (P = 9.1E-10) are near genes that encode distinct isoforms of diacylglycerol kinase. Rs780094 is in GCKR. We characterized the expression of these genes in gut, kidney, and bone, and demonstrate modulation of gene expression in bone in response to dietary calcium in mice. Our results shed new light on the genetics of calcium homeostasis.
C1 [O'Seaghdha, Conall M.; Wu, Hongsheng; Yang, Qiong; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[O'Seaghdha, Conall M.; Wu, Hongsheng; Yang, Qiong; Fox, Caroline S.] NHLBI, Ctr Populat Studies, Framingham, MA USA.
[O'Seaghdha, Conall M.] Massachusetts Gen Hosp, Div Renal, Boston, MA 02114 USA.
[Wu, Hongsheng; Yang, Qiong] Boston Univ, Dept Biostat, Boston, MA 02215 USA.
[Wu, Hongsheng] Univ Split, Sch Med, Dept Med Biol, Split, Croatia.
[Kapur, Karen; Kutalik, Zoltan; Mace, Aurelien; Bergmann, Sven] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland.
[Guessous, Idris; Bochud, Murielle] Univ Lausanne Hosp, Inst Social & Prevent Med IUMSP, Lausanne, Switzerland.
[Guessous, Idris; Theler, Jean-Marc] Univ Hosp Geneva, Dept Community Med & Primary Care & Emergency Med, Div Primary Care Med, Unit Populat Epidemiol, Geneva, Switzerland.
[Guessous, Idris] ASF, Geriatr Unit, Florence, Italy.
[Zuber, Annie Mercier; Stoudmann, Candice; Firsov, Dmitri; Bonny, Olivier] Univ Lausanne, Dept Pharmacol & Toxicol, Lausanne, Switzerland.
[Koettgen, Anna] Freiburg Univ Hosp, Div Renal, Freiburg, Germany.
[Koettgen, Anna; Kao, W. H. Linda] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Teumer, Alexander; Ernst, Florian D.; Voelker, Uwe; Schurmann, Claudia] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany.
[Kutalik, Zoltan; Mace, Aurelien; Bergmann, Sven] Swiss Inst Bioinformat, Lausanne, Switzerland.
[Mangino, Massimo; Spector, Tim D.] Kings Coll London, London, England.
[Dehghan, Abbas; Franco, Oscar H.; Hofman, Albert; Witteman, Jacqueline C. M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Zhang, Weihua; Chambers, John C.; Kooner, Jaspal S.] Ealing Gen Hosp, Catheter Lab, Southall, Middx, England.
[Zhang, Weihua; Chambers, John C.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
[Eiriksdottir, Gudny; Gudnason, Vilmundur; Smith, Albert V.] Iceland Heart Assoc Res Inst, Kopavogur, Iceland.
[Li, Guo; Siscovick, David S.; Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Tanaka, Toshiko] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Portas, Laura; Murgia, Federico; Pirastu, Mario] CNR Traversa La Crucca, Inst Populat Genet, Sassari, Italy.
[Lopez, Lorna M.; Davies, Gail; Starr, John M.; Deary, Ian J.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.
[Hayward, Caroline; Vitart, Veronique; Wright, Alan F.; Navarro, Pau] Univ Edinburgh, MRC IGMM, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.
[Lohman, Kurt] ClinPhenomics GmbH&Co KG, Cardiol Grp, Frankfurt, Germany.
[Matsuda, Koichi; Tanikawa, Chizu; Nakamura, Yusuke] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Mol Med Lab, Tokyo, Japan.
[Padmanabhan, Sandosh] Univ Glasgow, Div Cardiovasc & Med Sci, BHF Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland.
[Sorice, Rossella; Ruggiero, Daniela; Ciullo, Marina] CNR, Inst Genet & Biophys Adriano Buzzati Traverso, I-80125 Naples, Italy.
[Ulivi, Sheila; Girotto, Giorgia; d'Adamo, Adamo Pio; Robino, Antonietta; Gasparini, Paolo; Pirastu, Nicola] IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy.
[Brockhaus, A. Catharina; Gieger, Christian] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, Neuherberg, Germany.
[Brockhaus, A. Catharina] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany.
[Kleber, Marcus E.] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, D-89069 Ulm, Germany.
[Kleber, Marcus E.; Maerz, Winfried] Heidelberg Univ, Med Fac Mannheim, Mannheim Inst Publ Hlth Social & Prevent Med, Mannheim, Germany.
[Mahajan, Anubha; Morris, Andrew P.] Wellcome Trust Ctr Human Genet, Oxford, England.
[Gudnason, Vilmundur; Smith, Albert V.] Univ Iceland, Reykjavik, Iceland.
[Launer, Lenore J.; Harris, Tamara B.; Ferrucci, Luigi] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Boerwinckle, Eric] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA.
[Arking, Dan E.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA.
[Brown, Morris J.] Univ Cambridge, Cambridge Inst Med Res, Cambridge, England.
[Gaspoz, Jean-Michel] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Siscovick, David S.; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA.
[Siscovick, David S.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Vollenweider, Peter] Univ Lausanne Hosp, Dept Med, Lausanne, Switzerland.
[Zemunik, Tatijana; Kolcic, Ivana; Polasek, Ozren] Univ Split, Fac Med, Split, Croatia.
[Boban, Mladen] Univ Split, Fac Med, Dept Pharmacol, Split, Croatia.
[Brown, Edward M.; Ding, Jingzhong] Univ Hosp Geneva, Div Lab Med, Geneva, Switzerland.
[Estrada, Karol; Uitterlinden, Andre G.; Rivadeneira, Fernando] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA.
[Bandinelli, Stefania] Wellcome Trust Sanger Inst, Dept Human Genet, Cambridge, England.
[Hernandez, Dena; Singleton, Andrew B.] NIA, Mol Genet Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Meitinger, Thomas] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Human Genet, Neuherberg, Germany.
[Meitinger, Thomas] Wentworth Inst Technol, Dept Comp Sci & Networking, Boston, MA USA.
[Meisinger, Christa] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany.
[Chambers, John C.] Univ London Imperial Coll Sci Technol & Med, London, England.
[Boehm, Bernhard O.] Univ Ulm, Dept Internal Med 1, Med Ctr, D-89069 Ulm, Germany.
[Boehm, Bernhard O.] Univ London Imperial Coll Sci Technol & Med, LKC Sch Med, Singapore, Singapore.
[Boehm, Bernhard O.] Nanyang Technol Univ, Singapore 639798, Singapore.
[Winkelmann, Bernhard R.] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA.
[Huang, Jie] Univ Hosp Geneva, Dept Community Med & Primary Care & Emergency Med, Div Primary Care Med, Geneva, Switzerland.
[Wild, Sarah H.; Campbell, Harry; Rudan, Igor; Wilson, James F.] Univ Edinburgh, Sch Med, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
[Hannemann, Anke; Nauck, Matthias; Wallaschofski, Henri] Ernst Moritz Arndt Univ Greifswald, Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany.
[Biffar, Reiner] Univ Med Greifswald, Dept Prosthet Dent Gerostomatol & Dent Mat, Greifswald, Germany.
[Hoffmann, Wolfgang] Univ Med Greifswald, Inst Community Med, Greifswald, Germany.
[Shin, So-Youn] Wellcome Trust Sanger Inst, Hinxton, England.
[Lescuyer, Pierre] Wake Forest Sch Med, Dept Biostat Sci, Div Publ Hlth Sci, Winston Salem, NC USA.
[Henry, Hughes] Univ Lausanne Hosp, Clin Chem Lab, Lausanne, Switzerland.
[Munroe, Patricia B.] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.
[Maerz, Winfried] Synlab Ctr Lab Diagnost, Heidelberg, Germany.
[Lind, Lars] Univ Uppsala Hosp, Inst Med Sci, Uppsala, Sweden.
[Liu, Yongmei] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC USA.
[Kestenbaum, Bryan] Univ Washington, Dept Med, Div Nephrol, Seattle, WA 98195 USA.
[Kooner, Jaspal S.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Natl Heart & Lung Inst, Fac Med, London, England.
[Kooner, Jaspal S.] Imperial Coll Healthcare NHS Trust, London, England.
[Kao, W. H. Linda] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
[Bonny, Olivier] Univ Lausanne Hosp, Serv Nephrol, Lausanne, Switzerland.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
RP O'Seaghdha, CM (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA.
EM foxca@nhlbi.nih.gov; Murielle.Bochud@chuv.ch
RI Smith, Albert/K-5150-2015; ruggiero, daniela/K-5638-2016; Schurmann,
Claudia/L-1204-2016; Bochud, Murielle/A-3981-2010; mangino,
massimo/F-5134-2011; Hayward, Caroline/M-8818-2016; Padmanabhan,
Sandosh/S-3963-2016; Boban, Mladen/E-2777-2017; Kolcic,
Ivana/E-2713-2017; Colaus, PsyColaus/K-6607-2013; Gasparini,
Paolo/B-6173-2014; d'Adamo, Adamo Pio/G-4064-2011; Meisinger,
Christine/B-5358-2014; Singleton, Andrew/C-3010-2009; Yang,
Qiong/G-5438-2014; Boehm, Bernhard/F-8750-2015; Gudnason,
Vilmundur/K-6885-2015; Wilson, James F/A-5704-2009; Polasek,
Ozren/B-6002-2011; Meitinger, Thomas/O-1318-2015; Rivadeneira,
Fernando/O-5385-2015; Rudan, Igor/I-1467-2012
OI Kleber, Marcus/0000-0003-0663-7275; Dehghan, Abbas/0000-0001-6403-016X;
Pirastu, Nicola/0000-0002-5363-3886; Padmanabhan,
Sandosh/0000-0003-3869-5808; Gieger, Christian/0000-0001-6986-9554;
Meisinger, Christa/0000-0002-9026-6544; Girotto,
Giorgia/0000-0003-4507-6589; Navarro, Pau/0000-0001-5576-8584; Smith,
Albert/0000-0003-1942-5845; ruggiero, daniela/0000-0003-3898-7827;
Schurmann, Claudia/0000-0003-4158-9192; Bochud,
Murielle/0000-0002-5727-0218; mangino, massimo/0000-0002-2167-7470;
Hayward, Caroline/0000-0002-9405-9550; Kolcic,
Ivana/0000-0001-7918-6052; Lescuyer, Pierre/0000-0001-6986-8738;
d'Adamo, Adamo Pio/0000-0001-9367-4909; Gudnason,
Vilmundur/0000-0001-5696-0084; Wilson, James F/0000-0001-5751-9178;
Polasek, Ozren/0000-0002-5765-1862; Rivadeneira,
Fernando/0000-0001-9435-9441; Rudan, Igor/0000-0001-6993-6884
FU MIUR [5571/DSPAR/2002]; (FIRB) D. M. [718/Ric/2005];
[3100AO-116323/1,310000-112552]; [LSHG-CT-2006- 018947]; [108-1080315-
0302]; [N01-HC-25195]; [N02-HL-6-4278]; [N01AG62101]; [N01AG62103];
[N01AG62106]; [1R01AG032098-01A1]; [HHSN268200782096C];
[ICS110.1/RF97.71]; [263 MD 9164]; [263 MD 821336]; [N01-AG-1-2100];
[HHSN268201100005C]; [HHSN268201100006C]; [HHSN268201100007C];
[HHSN268201100008C]; [HHSN268201100009C]; [HHSN268201100010C];
[HHSN268201100011C]; [HSN268201100012C]; [01ZZ 0403];
[HEALTH-F2-2008-201865-GEFOS]; [HEALTH-F4-2007-201413];
[QLG2-CT-2002-01254]; [R01HL087641]; [R01HL59367]; [R01HL086694];
[U01HG004402]; [HHSN268200625226C]; [O3598/2-1]; [UL1RR025005];
[N01-HC-85239]; [N01-HC-85079]; [N01-HC-85080]; [N01-HC-85081];
[N01-HC-85082]; [N01-HC-85083]; [N01-HC-85084]; [N01-HC-85085];
[N01-HC-85086]; [N01-HC-35129]; [N01 HC-15103]; [N01 HC-55222]; [N01
- HC-75150]; [N01-HC-45133]; [HHSN268201200036C]; [HL080295];
[HL087652]; [HL105756]; [AG-023629]; [AG]; [SP/04/002.
G0700704/84698]; [LSHG-CT-2006-018947]; [01ZZ9603]; [01ZZ0103];
[01ZZ0403]; [03IS2061A]; [03ZIK012]; [175.010.2005.011];
[911-03-012]; [014-93-015]; [RIDE2. 050-060-810]; [vici, 918-76-619];
[Vasoplus-037254]; [FIRB - RBIN064YAT]; [LSHM-CT-2004-503485];
[WT064890]; [-15928]; [AG-20098]; [AG-027058]; [UL1RR033176];
[UL1TR000124]; [DK063491]; [33CSCO- 122661]; [3200BO-111361/2];
[WT081682]; [G20234]; [091746/Z/10/Z]; [G9521010D]; [PG/02/128];
[SP/04/002]; [PP00P3-133648]
FX All grant numbers for each human study and for the animal studies are
listed in the Acknowledgement section of the Supplementary material.
There is no specific funding for the GWAS meta-analysis itself. Grant
numbers: N01-AG-1-2100. HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C, and HSN268201100012C, R01HL087641,
R01HL59367, R01HL086694, U01HG004402, HHSN268200625226C. KO3598/2-1.
UL1RR025005. 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, HL080295, HL087652, HL105756, AG-023629, AG-15928,
AG-20098, AG-027058, UL1RR033176, UL1TR000124, DK063491. 33CSCO- 122661,
3200BO-111361/2, 3100AO-116323/1,310000-112552. LSHG-CT-2006- 018947.
108- 1080315-0302. LSHG-CT-2006-018947, 108-1080315- 0302. 108-1080315-
0302. N01-HC-25195. N02-HL-6-4278. N01AG62101, N01AG62103, N01AG62106.
1R01AG032098-01A1. HHSN268200782096C. ICS110.1/RF97.71. 263 MD 9164 and
263 MD 821336. SP/04/002. G0700704/84698. (MIUR) no. 5571/DSPAR/2002 and
(FIRB) D. M. no. 718/Ric/2005. LSHG-CT-2006-018947. 01ZZ9603, 01ZZ0103,
01ZZ0403, 03IS2061A, 03ZIK012. 175.010.2005.011, 911-03-012. 014-93-015;
RIDE2. 050-060-810. vici, 918-76-619. Vasoplus-037254. FIRB -
RBIN064YAT. LSHM-CT-2004-503485. WT064890, WT081682. 01ZZ9603, 01ZZ0103,
and 01ZZ 0403. 03IS2061A. 03ZIK012. HEALTH-F2-2008-201865-GEFOS.
HEALTH-F4-2007-201413. QLG2-CT-2002-01254. G20234. 091746/Z/10/Z.
G9521010D. PG/02/128. SP/04/002. SP/04/002. PP00P3-133648. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 51
TC 23
Z9 23
U1 1
U2 41
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD SEP
PY 2013
VL 9
IS 9
AR e1003796
DI 10.1371/journal.pgen.1003796
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA 226ZM
UT WOS:000325076600054
PM 24068962
ER
PT J
AU Phelan, JD
Saba, I
Zeng, H
Kosan, C
Messer, MS
Olsson, HA
Fraszczak, J
Hildeman, DA
Aronow, BJ
Moroy, T
Grimes, HL
AF Phelan, James D.
Saba, Ingrid
Zeng, Hui
Kosan, Christian
Messer, Malynda S.
Olsson, H. Andre
Fraszczak, Jennifer
Hildeman, David A.
Aronow, Bruce J.
Moeroey, Tarik
Grimes, H. Leighton
TI Growth factor independent-1 Maintains Notch1-Dependent Transcriptional
Programming of Lymphoid Precursors
SO PLOS GENETICS
LA English
DT Article
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ZINC-FINGER PROTEIN; HEMATOPOIETIC
STEM-CELLS; NOTCH SIGNALING CONTROLS; T-LINEAGE SPECIFICATION; C-MYC;
ACTIVATING MUTATIONS; ENRICHMENT ANALYSIS; TUMOR-SUPPRESSOR; REPRESSOR
GFI1
AB Growth factor independent 1 (Gfi1) is a transcriptional repressor originally identified as a gene activated in T-cell leukemias induced by Moloney-murine-leukemia virus infection. Notch1 is a transmembrane receptor that is frequently mutated in human T-cell acute lymphoblastic leukemia (T-ALL). Gfi1 is an important factor in the initiation and maintenance of lymphoid leukemias and its deficiency significantly impedes Notch dependent initiation of T-ALL in animal models. Here, we show that immature hematopoietic cells require Gfi1 to competently integrate Notch-activated signaling. Notch1 activation coupled with Gfi1 deficiency early in T-lineage specification leads to a dramatic loss of T-cells, whereas activation in later stages leaves development unaffected. In Gfi1 deficient multipotent precursors, Notch activation induces lethality and is cell autonomous. Further, without Gfi1, multipotent progenitors do not maintain Notch1-activated global expression profiles typical for T-lineage precursors. In agreement with this, we find that both lymphoid-primed multipotent progenitors (LMPP) and early T lineage progenitors (ETP) do not properly form or function in Gfi1(-/-) mice. These defects correlate with an inability of Gfi1(-/-) progenitors to activate lymphoid genes, including IL7R, Rag1, Flt3 and Notch1. Our data indicate that Gfi1 is required for hematopoietic precursors to withstand Notch1 activation and to maintain Notch1 dependent transcriptional programming to determine early T-lymphoid lineage identity.
C1 [Phelan, James D.; Messer, Malynda S.; Olsson, H. Andre; Hildeman, David A.; Grimes, H. Leighton] Cincinnati Childrens Hosp Med Ctr, Div Cellular & Mol Immunol, Cincinnati, OH 45229 USA.
[Saba, Ingrid; Kosan, Christian; Fraszczak, Jennifer; Moeroey, Tarik] Inst Rech Clin Montreal, Montreal, PQ H2W 1R7, Canada.
[Saba, Ingrid; Moeroey, Tarik] Inst Rech Clin Montreal, Dept Microbiol Infectiol & Immunol, Montreal, PQ H2W 1R7, Canada.
[Zeng, Hui] Capital Med Univ, Beijing Ditan Hosp, Inst Infect Dis, Beijing, Peoples R China.
[Aronow, Bruce J.] Cincinnati Childrens Hosp Med Ctr, Div Biomed Informat, Cincinnati, OH 45229 USA.
[Grimes, H. Leighton] Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol, Cincinnati, OH 45229 USA.
RP Phelan, JD (reprint author), NCI, Metab Branch, Bethesda, MD 20892 USA.
EM Tarik.Moroy@ircm.qc.ca; Lee.Grimes@cchmc.org
RI Hildeman, David/I-4884-2015; Kosan, Christian/C-1213-2017;
OI Hildeman, David/0000-0002-0421-8483; Kosan,
Christian/0000-0002-8387-3653; Grimes, H. Leighton/0000-0001-8162-6758
FU UC Cancer Therapeutics T32 training grant [T32-CA117846]; Canada
Research Chair (Tier 1); CIHR [MOP - 84238, MOP - 111011]; CRS;
CancerFree Kids; Leukemia and Lymphoma Society of America; NIH
[CA105152, CA159845]; Alex's Lemonade Stand
FX JDP was a Pelotonia Fellow
(http://cancer.osu.edu/research/researcheducation/pelotoniafellowshippro
gram/pages/index.aspx) in the Immunobiology Graduate Program at the
University of Cincinnati College of Medicine, who was also supported by
the UC Cancer Therapeutics T32 training grant (T32-CA117846). TM was
supported by a Canada Research Chair (Tier 1) and grants from the CIHR
(MOP - 84238, MOP - 111011, http://www.cihr-irsc.gc.ca/e/193.html) and
the CRS (http://www.src-crs.ca/en-CA). HLG was supported by the
CancerFree Kids (www.cancerfreekids.org/), Leukemia and Lymphoma Society
of America (http://www.lls.org/), NIH (CA105152, CA159845,
http://www.nih.gov) and Alex's Lemonade Stand
(http://www.alexslemonade.org). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 76
TC 12
Z9 12
U1 1
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7390
EI 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD SEP
PY 2013
VL 9
IS 9
AR e1003713
DI 10.1371/journal.pgen.1003713
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA 226ZM
UT WOS:000325076600004
PM 24068942
ER
PT J
AU Armstrong, AB
Segars, JH
AF Armstrong, Alicia Brooks
Segars, James H.
TI Correcting Reproductive Health Disparities in Women: An Opportunity to
Improve the Health of Future Generations
SO SEMINARS IN REPRODUCTIVE MEDICINE
LA English
DT Editorial Material
ID IN-VITRO FERTILIZATION; ASIAN ETHNICITY; DEVELOPMENTAL ORIGINS;
BLACK-WOMEN; OUTCOMES; TECHNOLOGY; WHITE
C1 [Armstrong, Alicia Brooks; Segars, James H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
RP Segars, JH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, CRC, Bldg 10,Room E1-3140,10 Ctr Dr, Bethesda, MD 20892 USA.
EM segarsj@mail.nih.gov
FU Intramural NIH HHS [ZIE HD008737-13]
NR 14
TC 0
Z9 0
U1 0
U2 0
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 1526-8004
J9 SEMIN REPROD MED
JI Semin. Reprod. Med.
PD SEP
PY 2013
VL 31
IS 5
BP 313
EP 315
DI 10.1055/s-0033-1348888
PG 3
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 198DV
UT WOS:000322903000002
PM 23934690
ER
PT J
AU Owen, CM
Goldstein, EH
Clayton, JA
Segars, JH
AF Owen, Carter M.
Goldstein, Ellen H.
Clayton, Janine A.
Segars, James H.
TI Racial and Ethnic Health Disparities in Reproductive Medicine: An
Evidence-Based Overview
SO SEMINARS IN REPRODUCTIVE MEDICINE
LA English
DT Article
DE racial disparities; ancestry informative markers; admixture;
infertility; transgenerational; epigenetic; developmental origins of
adult disease
ID ANCESTRY INFORMATIVE MARKERS; VITRO FERTILIZATION OUTCOMES; ADVERSE
BIRTH OUTCOMES; INFANT-MORTALITY-RATES; AFRICAN-AMERICAN;
BIOMEDICAL-RESEARCH; PERINATAL PERIODS; HUMAN-POPULATIONS;
GENETIC-STRUCTURE; PRETERM BIRTH
AB Racial and ethnic health disparities in reproductive medicine exist across the life span and are costly and burdensome to our healthcare system. Reduction and ultimate elimination of health disparities is a priority of the National Institutes of Health who requires reporting of race and ethnicity for all clinical research it supports. Given the increasing rates of admixture in our population, the definition and subsequent genetic significance of self-reported race and ethnicity used in health disparity research is not straightforward. Some groups have advocated using self-reported ancestry or carefully selected single-nucleotide polymorphisms, also known as ancestry informative markers, to sort individuals into populations. Despite the limitations in our current definitions of race and ethnicity in research, there are several clear examples of health inequalities in reproductive medicine extending from puberty and infertility to obstetric outcomes. We acknowledge that socioeconomic status, education, insurance status, and overall access to care likely contribute to the differences, but these factors do not fully explain the disparities. Epigenetics may provide the biologic link between these environmental factors and the transgenerational disparities that are observed. We propose an integrated view of health disparities across the life span and generations focusing on the metabolic aspects of fetal programming and the effects of environmental exposures. Interventions aimed at improving nutrition and minimizing adverse environmental exposures may act synergistically to reverse the effects of these epigenetic marks and improve the outcome of our future generations.
C1 [Owen, Carter M.] Univ Penn, Sch Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA.
[Goldstein, Ellen H.] Dartmouth Hitchcock Med Ctr, Dept Obstet & Gynecol, Lebanon, NH 03766 USA.
[Clayton, Janine A.] NIH, Off Res Womens Hlth, Bethesda, MD 20892 USA.
[Segars, James H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
RP Segars, JH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, CRC, Bldg 10,Room E1-3140,10 Ctr Dr, Bethesda, MD 20892 USA.
EM segarsj@mail.nih.gov
OI Owen, Carter Monique/0000-0002-5012-2706
FU Intramural NIH HHS [ZIE HD008737-13]
NR 76
TC 8
Z9 8
U1 0
U2 21
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 1526-8004
J9 SEMIN REPROD MED
JI Semin. Reprod. Med.
PD SEP
PY 2013
VL 31
IS 5
BP 317
EP 324
DI 10.1055/s-0033-1348889
PG 8
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 198DV
UT WOS:000322903000003
PM 23934691
ER
PT J
AU Sauerbrun-Cutler, MT
Segars, JH
AF Sauerbrun-Cutler, May-Tal
Segars, James H.
TI Do In Utero Events Contribute to Current Health Disparities in
Reproductive Medicine?
SO SEMINARS IN REPRODUCTIVE MEDICINE
LA English
DT Article
DE DOHaD; preterm labor; obesity; African Americans; preterm birth
ID POLYCYSTIC-OVARY-SYNDROME; INTRAUTERINE GROWTH RESTRICTION;
AFRICAN-AMERICAN WOMEN; PRETERM BIRTH; DEVELOPMENTAL ORIGINS; ADULT
DISEASE; OMEGA-3-FATTY-ACID SUPPLEMENTATION; EPIGENETIC MODIFICATION;
MATERNAL NUTRITION; PRENATAL EXPOSURE
AB Health disparities exist in reproductive medicine as discussed in detail in the subsequent articles of this issue; however, in most cases, the exact cause of these differences is unknown. Some of these disparities can be linked to environmental exposures such as alcohol and other hazardous toxic exposures (polycarbonate, pesticides, nicotine) in adults. In addition, low socioeconomic status, behavioral risk factors, and lack of education have been linked to poor obstetric and reproductive outcomes in minority groups. Aside from these various environmental exposures later in life, there is evidence that adverse events in utero could contribute to poor reproductive outcome in specific minority groups. We will focus on the developmental origins of health and disease as a possible causal mechanism for health disparities in reproductive diseases, as this perspective may suggest tractable solutions of how to address and eliminate these health disparities.
C1 [Sauerbrun-Cutler, May-Tal; Segars, James H.] St Lukes Roosevelt Hosp, Dept Obstet & Gynecol, New York, NY 10025 USA.
Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
RP Segars, JH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, CRC, Bldg 10,Room 1E3140,10 Ctr Dr, Bethesda, MD 20892 USA.
EM segarsj@mail.nih.gov
FU Intramural Research Division of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development
FX This work was supported by the Intramural Research Division of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development.
NR 68
TC 3
Z9 3
U1 1
U2 4
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 1526-8004
J9 SEMIN REPROD MED
JI Semin. Reprod. Med.
PD SEP
PY 2013
VL 31
IS 5
BP 325
EP 332
DI 10.1055/s-0033-1348890
PG 8
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 198DV
UT WOS:000322903000004
PM 23934692
ER
PT J
AU Ramnitz, MS
Lodish, MB
AF Ramnitz, Mary Scott
Lodish, Maya B.
TI Racial Disparities in Pubertal Development
SO SEMINARS IN REPRODUCTIVE MEDICINE
LA English
DT Article
DE puberty; menarche; Tanner stage; race
ID SECONDARY SEXUAL CHARACTERISTICS; BODY-MASS INDEX; NUTRITION EXAMINATION
SURVEY; HEALTH-EXAMINATION-SURVEY; OFFICE SETTINGS NETWORK;
BLOOD-INSTITUTE GROWTH; US CHILDREN; PEDIATRIC RESEARCH;
NATIONAL-HEALTH; BOGALUSA HEART
AB The question of whether or not children, particularly girls, are entering puberty earlier than they did in the past has been a concern in both the medical community and the general population. A secular trend analysis of the current data on pubertal timing in boys and girls is limited by variations in the study design, the population assessed, and the methods used to determine pubertal development. These differences present a challenge when interpreting the available data, especially when comparing multiple studies. The influence of race on pubertal timing and development had not been assessed before the 1970s. The purpose of this article is to review the reported variations in pubertal timing among different racial/ethnic groups. Data suggest African American girls enter puberty earlier and reach menarche earlier than Caucasian and Hispanic girls. In addition, the trend toward earlier timing of puberty seems to be occurring faster in African American girls compared with Caucasian girls over the past 25 years. While the mechanism and understanding of the cause of racial disparities in pubertal development remain to be discerned, genetic and/or environmental factors may play a role and require further investigation.
C1 [Ramnitz, Mary Scott; Lodish, Maya B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
RP Ramnitz, MS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, CRC, Room 1-3330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA.
EM ramnitzms@mail.nih.gov
FU Intramural Research Division of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development
FX This work was supported by the Intramural Research Division of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development.
NR 30
TC 5
Z9 6
U1 5
U2 14
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 1526-8004
J9 SEMIN REPROD MED
JI Semin. Reprod. Med.
PD SEP
PY 2013
VL 31
IS 5
BP 333
EP 339
DI 10.1055/s-0033-1348891
PG 7
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 198DV
UT WOS:000322903000005
PM 23934693
ER
PT J
AU Plowden, TC
Novak, CM
Spong, CY
AF Plowden, Torie C.
Novak, Christopher M.
Spong, Catherine Y.
TI Disparities in Obstetrical Outcomes in ART Pregnancies Compared with
Natural Conceptions
SO SEMINARS IN REPRODUCTIVE MEDICINE
LA English
DT Article
DE assisted reproduction; spontaneous conception; ethnic disparities
ID IN-VITRO-FERTILIZATION; ASSISTED REPRODUCTIVE TECHNOLOGY;
INTRACYTOPLASMIC SPERM INJECTION; LOW-BIRTH-WEIGHT; PRETERM BIRTH;
PERINATAL OUTCOMES; SINGLETON PREGNANCIES; ASIAN ETHNICITY;
CEREBRAL-PALSY; INTRAUTERINE INSEMINATION
AB Health disparities are observed in all fields of medicine and reproductive health is not immune to this phenomenon. The incidence of women using infertility treatments to conceive is increasing. Women undergoing assisted reproduction appear to be at increased risk of adverse outcomes, and minority women tend to be at even greater risk. This article examines several adverse obstetrical outcomes including preterm birth, congenital malformations, and preeclampsia among women receiving infertility treatments compared with those who conceive spontaneously. It will further examine societal costs associated with these procedures.
C1 [Plowden, Torie C.] Bayne Jones Army Community Hosp, Dept Obstet & Gynecol, Ft Polk, LA 71459 USA.
[Novak, Christopher M.] Ft Drum Obstet & Gynecol Clin, Watertown, NY USA.
[Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Plowden, TC (reprint author), Bayne Jones Army Community Hosp, Dept Obstet & Gynecol, 1585 3rd St, Ft Polk, LA 71459 USA.
EM tcomeaux@gmail.com
NR 61
TC 0
Z9 0
U1 4
U2 13
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 1526-8004
J9 SEMIN REPROD MED
JI Semin. Reprod. Med.
PD SEP
PY 2013
VL 31
IS 5
BP 340
EP 346
DI 10.1055/s-0033-1348892
PG 7
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 198DV
UT WOS:000322903000006
PM 23934694
ER
PT J
AU Catherino, WH
Eltoukhi, HM
Al-Hendy, A
AF Catherino, William H.
Eltoukhi, Heba M.
Al-Hendy, Ayman
TI Racial and Ethnic Differences in the Pathogenesis and Clinical
Manifestations of Uterine Leiomyoma
SO SEMINARS IN REPRODUCTIVE MEDICINE
LA English
DT Article
DE uterine leiomyoma; African American; ethnicity; molecular; risk factor
ID CATECHOL-O-METHYLTRANSFERASE; SMOOTH-MUSCLE-CELLS; AFRICAN-AMERICAN
WOMEN; GROWTH-FACTOR-BETA; GONADOTROPIN-RELEASING-HORMONE;
ACTIVATED-RECEPTOR-GAMMA; TRANS-RETINOIC ACID; MAJOR LIFE EVENTS; EKER
RAT MODEL; VITAMIN-D
AB Uterine leiomyomas are the most common benign gynecologic condition. The prevalence is three times more common among women of African ethnicity. Disparity in this disease is evidenced by earlier age of onset, greater severity of symptoms, and different response to treatment. Although the pathogenesis of disease development is not completely known, growing evidence focuses on investigating the molecular mechanisms in disease development and the influence of ethnicity. Variation in the expression levels or function of estrogen and progesterone receptors, polymorphism of genes involved in estrogen synthesis and/or metabolism (COMT, CYP17), retinoic acid nuclear receptors (retinoid acid receptor-, retinoid X receptor-), and aberrant expression of micro-RNAs (miRNAs) are some of the molecular mechanisms that may be involved. Nutritional factors, such as vitamin D deficiency, might also contribute to the higher incidence in dark skinned populations who are also commonly suffer from hypovitaminosis D. Culture and environmental difference might have a role in disease development. Further analysis and better understanding of these mechanisms will provide insight into the molecular basis of racial disparities in leiomyoma formation and will help to develop new innovations in leiomyoma treatment.
C1 [Catherino, William H.; Eltoukhi, Heba M.] NICHHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
[Catherino, William H.] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA.
[Eltoukhi, Heba M.] Suez Canal Univ, Dept Obstet & Gynecol, Ismailia, Egypt.
[Al-Hendy, Ayman] Meharry Med Coll, Ctr Womens Hlth Res, Dept Obstet & Gynecol, Nashville, TN 37208 USA.
RP Al-Hendy, A (reprint author), Meharry Med Coll, Ctr Womens Hlth Res, Dept Obstet & Gynecol, 1005 Dr DB Todd Jr Blvd, Nashville, TN 37208 USA.
EM Ahendy@MMC.edu
FU NIH
FX The authors acknowledge the support and assistance of Drs. DeCherney and
Zahn. This research was supported, in part, by NIH grants to authors
A.A. and W.C.
NR 128
TC 17
Z9 19
U1 2
U2 11
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 1526-8004
J9 SEMIN REPROD MED
JI Semin. Reprod. Med.
PD SEP
PY 2013
VL 31
IS 5
BP 370
EP 379
DI 10.1055/s-0033-1348896
PG 10
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 198DV
UT WOS:000322903000010
PM 23934698
ER
PT J
AU Mohiuddin, M
Singh, A
Corcoran, P
Thomas, M
Hoyt, R
Lewis, B
Clark, T
Eckhaus, M
Wolf, E
Reimann, K
Ayares, D
Horvath, K
AF Mohiuddin, Muhammad
Singh, Avneesh
Corcoran, Philip
Thomas, Marvin
Hoyt, Robert
Lewis, Billeta
Clark, Tannia
Eckhaus, Michael
Wolf, Eckhard
Reimann, Keith
Ayares, David
Horvath, Keith
TI Over 9 months graft survival of GTKO.hCD46tg.hTMtg pig heterotopic heart
xenograft in Anti CD40 (2C10) treated baboon
SO XENOTRANSPLANTATION
LA English
DT Meeting Abstract
CT Joint Congress of 12th International-Xenotransplantation-Association and
Organ Transplantation in ABO-incompatible and Hyperimmunized Recipients
CY NOV 10-13, 2013
CL Osaka, JAPAN
SP Int Xenotransplantat Assoc, Transplantat Soc, Int Xenotransplantat Assoc
C1 [Mohiuddin, Muhammad; Singh, Avneesh; Corcoran, Philip; Horvath, Keith] NHLBI, Cardiothorac Surg Res Program, NIH, Bethesda, MD 20892 USA.
[Thomas, Marvin; Lewis, Billeta; Eckhaus, Michael] NIH, DVR, ORS, Bethesda, MD 20892 USA.
[Hoyt, Robert; Clark, Tannia] NHLBI, LAMS, NIH, Bethesda, MD 20892 USA.
[Wolf, Eckhard] Univ Munich, Inst Mol Anim Breeding & Biotechnol, Munich, Germany.
[Reimann, Keith] Univ Massachusetts, Boston, MA 02125 USA.
[Ayares, David] Revivicor Inc, Blacksburgh, VA USA.
RI Mohiuddin, Muhammad/M-4642-2013
OI Mohiuddin, Muhammad/0000-0003-4654-783X
NR 0
TC 1
Z9 1
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0908-665X
EI 1399-3089
J9 XENOTRANSPLANTATION
JI Xenotransplantation
PD SEP
PY 2013
VL 20
IS 5
SI SI
BP 329
EP 329
PG 1
WC Medicine, Research & Experimental; Transplantation
SC Research & Experimental Medicine; Transplantation
GA 224YG
UT WOS:000324928400046
ER
PT J
AU Singh, A
Corcoran, P
Thomas, M
Hoyt, R
Lewis, B
Clark, T
Eckhaus, M
Reimann, K
Ayares, D
Horvath, K
Mohiuddin, M
AF Singh, Avneesh
Corcoran, Philip
Thomas, Marvin
Hoyt, Robert
Lewis, Billeta
Clark, Tannia
Eckhaus, Michael
Reimann, Keith
Ayares, David
Horvath, Keith
Mohiuddin, Muhammad
TI Low and tapering dose of anti CD40 (2C10 or 3A8) for 8-week duration
fails to extend GTKO.hCD46Tg pig to baboon cardiac xenograft survival
beyond 5 months
SO XENOTRANSPLANTATION
LA English
DT Meeting Abstract
CT Joint Congress of 12th International-Xenotransplantation-Association and
Organ Transplantation in ABO-incompatible and Hyperimmunized Recipients
CY NOV 10-13, 2013
CL Osaka, JAPAN
SP Int Xenotransplantat Assoc, Transplantat Soc, Int Xenotransplantat Assoc
C1 [Singh, Avneesh; Corcoran, Philip; Horvath, Keith; Mohiuddin, Muhammad] NHLBI, Cardiothorac Surg Res Program, NIH, Bethesda, MD 20892 USA.
[Thomas, Marvin; Lewis, Billeta; Eckhaus, Michael] NIH, DVR, ORS, Bethesda, MD 20892 USA.
[Clark, Tannia] NHLBI, LAMS, NIH, Bethesda, MD 20892 USA.
[Reimann, Keith] Univ Massachusetts, Boston, MA 02125 USA.
[Ayares, David] Revivicor Inc, Blacksburgh, VA USA.
RI Mohiuddin, Muhammad/M-4642-2013
OI Mohiuddin, Muhammad/0000-0003-4654-783X
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 0908-665X
EI 1399-3089
J9 XENOTRANSPLANTATION
JI Xenotransplantation
PD SEP
PY 2013
VL 20
IS 5
SI SI
BP 342
EP 342
PG 1
WC Medicine, Research & Experimental; Transplantation
SC Research & Experimental Medicine; Transplantation
GA 224YG
UT WOS:000324928400084
ER
PT J
AU Singh, A
Seavey, C
Corcoran, P
Lewis, B
Thomas, M
Hoyt, R
Ayares, D
Horvath, K
Mohiuddin, M
AF Singh, Avneesh
Seavey, Caleb
Corcoran, Philip
Lewis, Billeta
Thomas, Marvin
Hoyt, Robert
Ayares, David
Horvath, Keith
Mohiuddin, Muhammad
TI Pig to baboon heterotopic cardiac xenotransplantation: Potential role of
baboon CD4+CD25(Hi) FOxP3+T regulatory cells in long-term graft survival
SO XENOTRANSPLANTATION
LA English
DT Meeting Abstract
CT Joint Congress of 12th International-Xenotransplantation-Association and
Organ Transplantation in ABO-incompatible and Hyperimmunized Recipients
CY NOV 10-13, 2013
CL Osaka, JAPAN
SP Int Xenotransplantat Assoc, Transplantat Soc, Int Xenotransplantat Assoc
C1 [Singh, Avneesh; Seavey, Caleb; Corcoran, Philip; Horvath, Keith; Mohiuddin, Muhammad] NHLBI, Cardiothorac Surg Res Program, NIH, Bethesda, MD 20892 USA.
[Lewis, Billeta; Thomas, Marvin] NIH, DVR, ORS, Bethesda, MD 20892 USA.
[Hoyt, Robert] NHLBI, LAMS, NIH, Bethesda, MD 20892 USA.
[Ayares, David] Revivicor Inc, Blacksburgh, VA USA.
RI Mohiuddin, Muhammad/M-4642-2013
OI Mohiuddin, Muhammad/0000-0003-4654-783X
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 0908-665X
EI 1399-3089
J9 XENOTRANSPLANTATION
JI Xenotransplantation
PD SEP
PY 2013
VL 20
IS 5
SI SI
BP 343
EP 343
PG 1
WC Medicine, Research & Experimental; Transplantation
SC Research & Experimental Medicine; Transplantation
GA 224YG
UT WOS:000324928400085
ER
PT J
AU Mohiuddin, M
AF Mohiuddin, Muhammad
TI Ex vivo expanded Tregs suppress the baboon anti-pig T and B cell
response
SO XENOTRANSPLANTATION
LA English
DT Meeting Abstract
CT Joint Congress of 12th International-Xenotransplantation-Association and
Organ Transplantation in ABO-incompatible and Hyperimmunized Recipients
CY NOV 10-13, 2013
CL Osaka, JAPAN
SP Int Xenotransplantat Assoc, Transplantat Soc, Int Xenotransplantat Assoc
C1 [Mohiuddin, Muhammad] NHLBI, Cardiothorac Surg Res Program, NIH, Bethesda, MD 20892 USA.
RI Mohiuddin, Muhammad/M-4642-2013
OI Mohiuddin, Muhammad/0000-0003-4654-783X
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 0908-665X
EI 1399-3089
J9 XENOTRANSPLANTATION
JI Xenotransplantation
PD SEP
PY 2013
VL 20
IS 5
SI SI
BP 349
EP 349
PG 1
WC Medicine, Research & Experimental; Transplantation
SC Research & Experimental Medicine; Transplantation
GA 224YG
UT WOS:000324928400104
ER
PT J
AU Clark, T
Singh, A
Corcoran, P
Thomas, M
Hoyt, R
Lewis, B
Horvath, K
Mohiuddin, M
AF Clark, Tannia
Singh, Avneesh
Corcoran, Philip
Thomas, Marvin
Hoyt, Robert
Lewis, Billeta
Horvath, Keith
Mohiuddin, Muhammad
TI Use of echocardiography to assess heterotopic cardiac xenograft function
and clot reduction therapeutic intervention in a transgenic pig to
baboon model
SO XENOTRANSPLANTATION
LA English
DT Meeting Abstract
CT Joint Congress of 12th International-Xenotransplantation-Association and
Organ Transplantation in ABO-incompatible and Hyperimmunized Recipients
CY NOV 10-13, 2013
CL Osaka, JAPAN
SP Int Xenotransplantat Assoc, Transplantat Soc, Int Xenotransplantat Assoc
C1 [Clark, Tannia; Hoyt, Robert; Horvath, Keith; Mohiuddin, Muhammad] NHLBI, LAMS, NIH, Bethesda, MD 20892 USA.
[Clark, Tannia; Singh, Avneesh; Corcoran, Philip; Thomas, Marvin; Hoyt, Robert; Lewis, Billeta; Horvath, Keith; Mohiuddin, Muhammad] Revivicor Inc, Blacksburgh, VA USA.
[Singh, Avneesh; Corcoran, Philip] NHLBI, Cardiothorac Surg Res Program, NIH, Bethesda, MD 20892 USA.
[Thomas, Marvin; Lewis, Billeta] NIH, DVR, ORS, Bethesda, MD 20892 USA.
RI Mohiuddin, Muhammad/M-4642-2013
OI Mohiuddin, Muhammad/0000-0003-4654-783X
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 0908-665X
EI 1399-3089
J9 XENOTRANSPLANTATION
JI Xenotransplantation
PD SEP
PY 2013
VL 20
IS 5
SI SI
BP 360
EP 360
PG 1
WC Medicine, Research & Experimental; Transplantation
SC Research & Experimental Medicine; Transplantation
GA 224YG
UT WOS:000324928400134
ER
PT J
AU Corcoran, P
Singh, A
Lewis, B
Thomas, M
Clark, T
Hoyt, R
Horvath, K
Mohiuddin, M
AF Corcoran, Philip
Singh, Avneesh
Lewis, Billeta
Thomas, Marvin
Clark, Tannia
Hoyt, Robert
Horvath, Keith
Mohiuddin, Muhammad
TI Telemetry, echocardiography and manual palpation of heterotopic cardiac
xenograft together improves the measurement accuracy of graft
contractility
SO XENOTRANSPLANTATION
LA English
DT Meeting Abstract
CT Joint Congress of 12th International-Xenotransplantation-Association and
Organ Transplantation in ABO-incompatible and Hyperimmunized Recipients
CY NOV 10-13, 2013
CL Osaka, JAPAN
SP Int Xenotransplantat Assoc, Transplantat Soc, Int Xenotransplantat Assoc
C1 [Corcoran, Philip; Singh, Avneesh; Horvath, Keith; Mohiuddin, Muhammad] NHLBI, Cardiothorac Surg Res Program, NIH, Bethesda, MD 20892 USA.
[Lewis, Billeta; Thomas, Marvin] NIH, DVR, ORS, Bethesda, MD 20892 USA.
NHLBI, LAMS, NIH, Bethesda, MD 20892 USA.
[Clark, Tannia; Hoyt, Robert] Revivicor Inc, Blacksburgh, VA USA.
RI Mohiuddin, Muhammad/M-4642-2013
OI Mohiuddin, Muhammad/0000-0003-4654-783X
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 0908-665X
EI 1399-3089
J9 XENOTRANSPLANTATION
JI Xenotransplantation
PD SEP
PY 2013
VL 20
IS 5
SI SI
BP 378
EP 378
PG 1
WC Medicine, Research & Experimental; Transplantation
SC Research & Experimental Medicine; Transplantation
GA 224YG
UT WOS:000324928400187
ER
PT J
AU Ouimet, MC
Pradhan, AK
Simons-Morton, BG
Divekar, G
Mehranian, H
Fisher, DL
AF Ouimet, Marie Claude
Pradhan, Anuj K.
Simons-Morton, Bruce G.
Divekar, Gautam
Mehranian, Hasmik
Fisher, Donald L.
TI The effect of male teenage passengers on male teenage drivers: Findings
from a driving simulator study
SO ACCIDENT ANALYSIS AND PREVENTION
LA English
DT Article
DE Driving; Risky behavior; Social influence; Peers; Adolescence; Male
ID SOCIAL FACILITATION; SENSATION-SEEKING; EYE-MOVEMENTS; ADOLESCENT
SMOKING; PEER INFLUENCES; MERE PRESENCE; RISK-TAKING; SELF-ESTEEM;
BEHAVIOR; DRINKING
AB Studies have shown that teenage drivers are less attentive, more frequently exhibit risky driving behavior, and have a higher fatal crash risk in the presence of peers. The effects of direct peer pressure and conversation on young drivers have been examined. Little is known about the impact on driving performance of the presence of a non-interacting passenger and subtle modes of peer influence, such as perceived social norms. The goal of this study was to examine if teenagers would engage in more risky driving practices and be less attentive in the presence of a passenger (vs. driving alone) as well as with a risk-accepting (vs. risk-averse) passenger. A confederate portrayed the passenger's characteristics mainly by his non-verbal attitude. The relationship between driver characteristics and driving behavior in the presence of a passenger was also examined. Thirty-six male participants aged 16-17 years old were randomly assigned to drive with a risk-accepting or risk-averse passenger. Main outcomes included speed, headway, gap acceptance, eye glances at hazards, and horizontal eye movement. Driver characteristics such as tolerance of deviance, susceptibility to peer pressure, and self-esteem were measured. Compared to solo driving, the presence of a passenger was associated with significantly fewer eye glances at hazards and a trend for fewer horizontal eye movements. Contrary to the hypothesis, however, Passenger Presence was associated with waiting for a greater number of vehicles to pass before initiating a left turn. Results also showed, contrary to the hypothesis, that participants with the risk-accepting passenger maintained significantly longer headway with the lead vehicle and engaged in more eye glances at hazards than participants with the risk-averse passenger. Finally, when driving with the passenger, earlier initiation of a left turn in a steady stream of oncoming vehicles was significantly associated with higher tolerance of deviance and susceptibility to peer pressure, while fewer eye glances at hazards was linked to lower self-esteem. While the results of this study were mixed, they suggest that the presence of a teenage passenger can affect some aspects of teenage driver behavior even in the absence of overt pressure and distraction. Results are discussed in relation to theoretical concepts of social influence and social facilitation models. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Ouimet, Marie Claude] Univ Sherbrooke, Fac Med & Hlth Sci, Longueuil, PQ J4A 0A8, Canada.
[Pradhan, Anuj K.; Simons-Morton, Bruce G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA.
[Divekar, Gautam; Mehranian, Hasmik; Fisher, Donald L.] Univ Massachusetts, Dept Mech & Ind Engn, Amherst, MA 01003 USA.
RP Ouimet, MC (reprint author), Univ Sherbrooke, Fac Med & Hlth Sci, 150 Charles Lemoyne Pl Suite 200, Longueuil, PQ J4A 0A8, Canada.
EM Marie.Claude.Ouimet@USherbrooke.ca
OI Pradhan, Anuj/0000-0002-7612-4208; Simons-Morton,
Bruce/0000-0003-1099-6617
FU Intramural NIH HHS [ZIA HD001707-15]; PHS HHS [HHSN267200700281P]
NR 57
TC 17
Z9 17
U1 1
U2 40
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0001-4575
J9 ACCIDENT ANAL PREV
JI Accid. Anal. Prev.
PD SEP
PY 2013
VL 58
BP 132
EP 139
DI 10.1016/j.aap.2013.04.024
PG 8
WC Ergonomics; Public, Environmental & Occupational Health; Social
Sciences, Interdisciplinary; Transportation
SC Engineering; Public, Environmental & Occupational Health; Social
Sciences - Other Topics; Transportation
GA 221KE
UT WOS:000324657000018
PM 23727554
ER
PT J
AU Taylor, T
Pradhan, AK
Divekar, G
Romoser, M
Muttart, J
Gomez, R
Pollatsek, A
Fisher, DL
AF Taylor, T.
Pradhan, A. K.
Divekar, G.
Romoser, M.
Muttart, J.
Gomez, R.
Pollatsek, A.
Fisher, D. L.
TI The view from the road: The contribution of on-road glance-monitoring
technologies to understanding driver behavior
SO ACCIDENT ANALYSIS AND PREVENTION
LA English
DT Article
DE On-road; Eye-tracking; Eye movements; Glance-monitoring; Hazard
anticipation; Attention maintenance; Novice driver; Older driver;
Distraction; Automobile crashes
ID EXPERIENCED DRIVERS; EYE-MOVEMENTS; VISUAL-SEARCH; NOVICE DRIVERS; OLDER
DRIVERS; CRASH RISK; ATTENTION; PATTERNS; VEHICLE; DISTRACTION
AB Using glance-monitoring technologies for on-road studies is an excellent way to investigate driver behaviors in an ecologically valid setting. Recent advances in glance-monitoring technologies have made it possible to conduct on-road studies of drivers' glance behavior that heretofore were simply not possible. Yet it is not always easy to determine which glance-monitoring technology to use for a particular application. Here, we first identify the generic capabilities of the various glance-monitoring technologies. We then describe how particular glance-monitoring technologies have been used in the field to (a) identify the skill deficiencies of novice and older drivers, (b) evaluate the effectiveness of training programs that are designed to reduce deficits in these skills, and (c) address interface issues both inside (e.g., collision warning systems) and outside (e.g., yield markings) the vehicle. The limitations and advantages of on-road eye-tracking and the associated glance-monitoring technologies are identified throughout. A comparison, where possible, is made between the results of on-road eye-tracking studies of drivers' behaviors and the results of those studies conducted in the laboratory. Overall, the use of appropriate on-road glance-monitoring technologies has greatly enhanced our theoretical understanding of why drivers behave the way they do, and this knowledge has paved the way for significant improvements in road user safety. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Taylor, T.; Divekar, G.; Romoser, M.; Muttart, J.; Gomez, R.; Fisher, D. L.] Univ Massachusetts, Dept Mech & Ind Engn, Amherst, MA 01003 USA.
[Pradhan, A. K.] NIH, Bethesda, MD 20892 USA.
[Pollatsek, A.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA.
RP Taylor, T (reprint author), Univ Massachusetts, Dept Mech & Ind Engn, Amherst, MA 01003 USA.
EM fisher@ecs.umass.edu; anujkp@gmail.com; gautamdivekar20000@gmail.com;
mromoser@ecs.umass.edu; jmuttart@engin.umass.edu;
ragomez@engin.umass.edu; pollatsek@psych.umass.edu; fisher@ecs.umass.edu
OI Pradhan, Anuj/0000-0002-7612-4208
FU NICHD NIH HHS [R01HD057153-01]
NR 76
TC 15
Z9 18
U1 2
U2 30
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0001-4575
J9 ACCIDENT ANAL PREV
JI Accid. Anal. Prev.
PD SEP
PY 2013
VL 58
BP 175
EP 186
DI 10.1016/j.aap.2013.02.008
PG 12
WC Ergonomics; Public, Environmental & Occupational Health; Social
Sciences, Interdisciplinary; Transportation
SC Engineering; Public, Environmental & Occupational Health; Social
Sciences - Other Topics; Transportation
GA 221KE
UT WOS:000324657000023
PM 23548549
ER
PT J
AU Pletnev, VZ
Pletneva, NV
Lukyanov, KA
Souslova, EA
Fradkov, AF
Chudakov, DM
Chepurnykh, T
Yampolsky, IV
Wlodawer, A
Dauter, Z
Pletnev, S
AF Pletnev, Vladimir Z.
Pletneva, Nadya V.
Lukyanov, Konstantin A.
Souslova, Ekaterina A.
Fradkov, Arkady F.
Chudakov, Dmitry M.
Chepurnykh, Tatyana
Yampolsky, Ilia V.
Wlodawer, Alexander
Dauter, Zbigniew
Pletnev, Sergei
TI Structure of the red fluorescent protein from a lancelet (Branchiostoma
lanceolatum): a novel GYG chromophore covalently bound to a nearby
tyrosine
SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
LA English
DT Article
ID GFP-LIKE PROTEINS; STATE PROTON-TRANSFER; CIS PEPTIDE-BONDS;
CRYSTAL-STRUCTURE; AMPHIOXUS GENOME; GREEN; EVOLUTION; VARIANTS; FAMILY;
CORAL
AB A key property of proteins of the green fluorescent protein (GFP) family is their ability to form a chromophore group by post-translational modifications of internal amino acids, e. g. Ser65-Tyr66-Gly67 in GFP from the jellyfish Aequorea victoria (Cnidaria). Numerous structural studies have demonstrated that the green GFP-like chromophore represents the 'core' structure, which can be extended in red-shifted proteins owing to modifications of the protein backbone at the first chromophore-forming position. Here, the three-dimensional structures of green laGFP (lambda(ex)/lambda(em) = 502/511 nm) and red laRFP (lambda(ex)/lambda(em) similar or equal to 521/592 nm), which are fluorescent proteins (FPs) from the lancelet Branchiostoma lanceolatum (Chordata), were determined together with the structure of a red variant laRFP-Delta S83 (deletion of Ser83) with improved folding. Lancelet FPs are evolutionarily distant and share only similar to 20% sequence identity with cnidarian FPs, which have been extensively characterized and widely used as genetically encoded probes. The structure of red-emitting laRFP revealed three exceptional features that have not been observed in wild-type fluorescent proteins from Cnidaria reported to date: (i) an unusual chromophore-forming sequence Gly58-Tyr59-Gly60, (ii) the presence of Gln211 at the position of the conserved catalytic Glu (Glu222 in Aequorea GFP), which proved to be crucial for chromophore formation, and (iii) the absence of modifications typical of known red chromophores and the presence of an extremely unusual covalent bond between the Tyr59 C-beta atom and the hydroxyl of the proximal Tyr62. The impact of this covalent bond on the red emission and the large Stokes shift (similar to 70 nm) of laRFP was verified by extensive structure-based site-directed mutagenesis.
C1 [Pletnev, Vladimir Z.; Pletneva, Nadya V.; Lukyanov, Konstantin A.; Souslova, Ekaterina A.; Fradkov, Arkady F.; Chudakov, Dmitry M.; Chepurnykh, Tatyana; Yampolsky, Ilia V.] Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow, Russia.
[Wlodawer, Alexander] NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA.
[Dauter, Zbigniew; Pletnev, Sergei] NCI, Synchrotron Radiat Res Ctr, Macromol Crystallog Lab, Argonne, IL 60439 USA.
[Pletnev, Sergei] SAIC Frederick, Basic Res Program, Argonne, IL 60439 USA.
RP Pletnev, VZ (reprint author), Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow, Russia.
EM vzpletnev@gmail.com; pletnevs@mail.nih.gov
RI Chudakov, Dmitriy/G-7741-2014; Pletneva, Nadya/F-7839-2014; Pletnev,
Vladimir/Q-6151-2016; Yampolsky, Ilia/R-6798-2016
OI Chudakov, Dmitriy/0000-0003-0430-790X; Yampolsky,
Ilia/0000-0003-2558-2476
FU US Department of Energy, Office of Science, Office of Basic Energy
Sciences [W-31-109-Eng-38]; National Cancer Institute, National
Institutes of Health (NIH) [HHSN261200800001E]; Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research; Russian Foundation for Basic Research [12-04-31615]; Ministry
of Education and Science of the Russian Federation [14.512.11.0052]
FX Diffraction experiments were carried out on beamline 22-ID of the
Southeast Regional Collaborative Access Team (SER-CAT) located at the
Advanced Photon Source, Argonne National Laboratory. Use of the APS was
supported by the US Department of Energy, Office of Science, Office of
Basic Energy Sciences under Contract No. W-31-109-Eng-38. This project
has been supported in part with Federal funds from the National Cancer
Institute, National Institutes of Health (NIH) contract No.
HHSN261200800001E, by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research, by a grant from
the Russian Foundation for Basic Research 12-04-31615 and by the
Ministry of Education and Science of the Russian Federation (project
14.512.11.0052). The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does the mention of trade names, commercial products, or
organizations imply endorsement by the US Government.
NR 53
TC 4
Z9 4
U1 1
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0907-4449
J9 ACTA CRYSTALLOGR D
JI Acta Crystallogr. Sect. D-Biol. Crystallogr.
PD SEP
PY 2013
VL 69
BP 1850
EP 1860
DI 10.1107/S0907444913015424
PN 9
PG 11
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biophysics; Crystallography
SC Biochemistry & Molecular Biology; Biophysics; Crystallography
GA 223PG
UT WOS:000324818000022
PM 23999308
ER
PT J
AU Swanson, CA
Pearce, EN
AF Swanson, Christine A.
Pearce, Elizabeth N.
TI Iodine Insufficiency: A Global Health Problem?
SO ADVANCES IN NUTRITION
LA English
DT Editorial Material
ID INFANTS; WOMEN
AB As a result of collaborative efforts with international organizations and the salt industry, many developing and developed countries practice universal salt iodization (USI) or have mandatory salt fortification programs. As a consequence, the prevalence of iodine deficiency decreased dramatically. The United States and Canada are among the few developed countries that do not practice USI. Such an undertaking would require evidence of deficiency among vulnerable population groups, including pregnant women, newborns, and developing infants. Government agencies in the United States rely heavily on data from NHANES to assess the iodine status of the general population and pregnant women in particular. NHANES data suggest that pregnant women in the United States remain mildly deficient This is important, because the developing fetus is dependent on maternal iodine intake for normal brain development throughout pregnancy. Professional societies have recommended that pregnant and lactating women, or those considering pregnancy, consume a supplement providing 150 mu g iodine daily. The United States and Canada collaborate on the daily recommended intake and are also confronted with the challenge of identifying the studies needed to determine if USI is likely to be beneficial to vulnerable population groups without exposing them to harm.
C1 [Swanson, Christine A.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
[Pearce, Elizabeth N.] Boston Univ, Sch Med, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA.
RP Swanson, CA (reprint author), NIH, Off Dietary Supplements, Bldg 10, Bethesda, MD 20892 USA.
FU American Society for Nutrition
FX This article is a summary of the symposium, "Iodine Insufficiency A
Global Health Problem?," held April 21, 2013, at the ASN Scientific
Sessions and Annual Meeting at Experimental Biology 2013 in Boston, MA.
The symposium was sponsored by the American Society for Nutrition The
organizer has indicated that related reviews of this symposium will be
submitted for publication in upcoming issues of Advances in Nutrition.
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PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 2161-8313
EI 2156-5376
J9 ADV NUTR
JI Adv. Nutr.
PD SEP
PY 2013
VL 4
IS 5
BP 533
EP 535
DI 10.3945/an.113.004192
PG 3
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 217KH
UT WOS:000324357900008
PM 24038248
ER
PT J
AU Gaine, PC
Balentine, DA
Erdman, JW
Dwyer, JT
Ellwood, KC
Hu, FB
Russell, RM
AF Gaine, P. Courtney
Balentine, Douglas A.
Erdman, John W., Jr.
Dwyer, Johanna T.
Ellwood, Kathleen C.
Hu, Frank B.
Russell, Robert M.
TI Are Dietary Bioactives Ready for Recommended Intakes?
SO ADVANCES IN NUTRITION
LA English
DT Editorial Material
AB Research has shown that numerous dietary bioactive components that are not considered essential may still be beneficial to health. The dietary reference intake (DRI) process has been applied to nonessential nutrients, such as fiber, yet the majority of bioactive components await a recommended intake. Despite a plethora of new research over the past several years on the health effects of bioactives, it is possible that the field may never reach a point where the current DRI framework is suitable for these food components. If bioactives are to move toward dietary guidance, they will likely require an alternative path to get there.
C1 [Gaine, P. Courtney] Int Life Sci Inst, North Amer Branch, Washington, DC USA.
[Balentine, Douglas A.] Unilever, Englewood Cliffs, NJ USA.
[Erdman, John W., Jr.] Univ Illinois, Urbana, IL 61801 USA.
[Dwyer, Johanna T.] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Ellwood, Kathleen C.] Coll Southern Maryland, La Plata, MD USA.
[Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA.
[Russell, Robert M.] Tufts Univ, Boston, MA 02111 USA.
[Russell, Robert M.] NIH, Bethesda, MD 20892 USA.
RP Gaine, PC (reprint author), Int Life Sci Inst, North Amer Branch, Washington, DC USA.
EM cgaine@ilsi.org
OI Dwyer, Johanna/0000-0002-0783-1769
FU American Society for Nutrition; ASN Dietary Bioactives RIS; North
American Branch of the International Life Sciences Institute's Committee
on Flavonoids
FX This article is a summary of the symposium "Are Dietary Bioactives Ready
for Recommended Intakes?" held April 21, 2013, at the ASN Scientific
Sessions and Annual Meeting at Experimental Biology 2013 in Boston, MA.
The symposium was sponsored by the American Society for Nutrition, the
ASN Dietary Bioactives RIS, and the North American Branch of the
International Life Sciences Institute's Committee on Flavonoids This is
a free access article, distributed under terms
(http.//www.nutrition.org/publications/guidelines-and-policies/license/)
that permit unrestricted noncommercial use, distribution, and
reproduction in any medium, provided the original work is properly
cited.
NR 0
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U1 0
U2 4
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 2161-8313
EI 2156-5376
J9 ADV NUTR
JI Adv. Nutr.
PD SEP
PY 2013
VL 4
IS 5
BP 539
EP 541
DI 10.3945/an.113.004226
PG 3
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 217KH
UT WOS:000324357900010
PM 24038250
ER
PT J
AU Webb, D
Leahy, MM
Milner, JA
Allison, DB
Dodd, KW
Gaine, PC
Matthews, RAJ
Schneeman, BO
Tucker, KL
Young, SS
AF Webb, Densie
Leahy, Margaret M.
Milner, John A.
Allison, David B.
Dodd, Kevin W.
Gaine, P. Courtney
Matthews, Robert A. J.
Schneeman, Barbara O.
Tucker, Katherine L.
Young, S. Stanley
TI Strategies to Optimize the Impact of Nutritional Surveys and
Epidemiological Studies
SO ADVANCES IN NUTRITION
LA English
DT Editorial Material
AB The development of nutrition and health guidelines and policies requires reliable scientific information. Unfortunately, theoretical considerations and empirical evidence indicate that a large percentage of science-based claims rely on studies that fail to replicate. The session "Strategies to Optimize the Impact of Nutrition Surveys and Epidemiological Studies" focused on the elements of design, interpretation, and communication of nutritional surveys and epidemiological studies to enhance and encourage the production of reliable, objective evidence for use in developing dietary guidance for the public. The speakers called for more transparency of research, raw data, consistent data-staging techniques, and improved data analysis. New approaches to collecting data are urgently needed to increase the credibility and utility of findings from nutrition epidemiological studies. Such studies are critical for furthering our knowledge and understanding of the effects of diet on health.
C1 [Leahy, Margaret M.] Coca Cola Co, Atlanta, GA USA.
[Milner, John A.] ARS, USDA, Beltsville, MD USA.
[Allison, David B.] Univ Alabama Birmingham, Birmingham, AL USA.
[Dodd, Kevin W.] NCI, Bethesda, MD 20892 USA.
[Gaine, P. Courtney] Int Life Sci Inst, North Amer Branch, Washington, DC USA.
[Matthews, Robert A. J.] Aston Univ, Birmingham B4 7ET, W Midlands, England.
[Schneeman, Barbara O.] Univ Calif Davis, Davis, CA 95616 USA.
[Tucker, Katherine L.] Northeastern Univ, Boston, MA 02115 USA.
[Young, S. Stanley] Natl Inst Stat Sci, Res Triangle Pk, NC USA.
EM dwebb1@austin.rr.com
FU American Society for Nutrition; North American Branch of the
International Life Sciences Institute's Committee on Carbohydrates;
Frontiers Foundation; Federal Trade Commission
FX This article is a summary of the symposium "Strategies to Optimize the
Impact of Nutritional Surveys and Epidemiological Studies" held April
20, 2013 at the ASN Scientific Sessions and Annual Meeting at
Experimental Biology 2013 in Boston, MA. The symposium was sponsored by
the American Society for Nutrition and the North American Branch of the
International Life Sciences Institute's Committee on Carbohydrates. This
is a free access article, distributed under terms
(http://www.nutrition.org/publications/guidelines-and-policies/license/)
that permit unrestricted noncommercial use, distribution, and
reproduction in any medium, provided the original work is properly
cited.; Author disclosures: M. M. Leahy is Vice-Chair of International
Life Sciences Institute (ILSI) North America's Carbohydrates Committee.
J. A. Milner is an ILSI Global, IFIC, and McCormick Science Institute
Board Member. D B. Allison has received financial and other benefits
from the Frontiers Foundation, Federal Trade Commission, and other
government, nonprofit, and for-profit organizations. K. L Tucker is a
scientific advisor to (ILSI North America and has received support from
the Kraft Foods Group. S. S. Young is a member of the OmicSoft
Scientific Advisory and the AJCN Editorial Boards. K. W. Dodd, P. C.
Gaine, R. A. J. Matthews, and B. O. Schneeman, no conflicts of interest.
NR 0
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PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 2161-8313
EI 2156-5376
J9 ADV NUTR
JI Adv. Nutr.
PD SEP
PY 2013
VL 4
IS 5
BP 545
EP 547
DI 10.3945/an.113.004259
PG 3
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 217KH
UT WOS:000324357900012
PM 24038252
ER
PT J
AU Cogswell, ME
Elliott, P
Wang, CY
Rhodes, DG
Pfeiffer, CM
Loria, CM
AF Cogswell, Mary E.
Elliott, Paul
Wang, Chia-Yih
Rhodes, Donna G.
Pfeiffer, Christine M.
Loria, Catherine M.
TI Assessing US Sodium Intake through Dietary Data and Urine Biomarkers
SO ADVANCES IN NUTRITION
LA English
DT Editorial Material
ID POTASSIUM EXCRETION; SPECIMEN; ADULTS
AB Sodium intake is related to blood pressure, an established risk factor for heart disease and stroke. Reducing intake may save billions in United States health care dollars annually. Efforts targeting sodium reductions make accurate monitoring vital, yet limited information exists on the accuracy of the current data to assess sodium intake in the United States population. In this symposium, new findings were presented on the accuracy of estimating population 24-h urinary excretion of sodium from spot urine specimens or sodium intake from 24-h dietary recalls. Differences in accuracy by sex, BMI, and race were apparent as well as by timing of spot urine collections. Although some published equations appear promising for estimating group means, others are biased. Individual estimates of sodium intake were highly variable and adjustment for within-individual variation in intake is required for estimating population prevalence or percentiles. Estimates indicated United States sodium intake remains high.
C1 [Cogswell, Mary E.; Pfeiffer, Christine M.] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA.
[Elliott, Paul] Univ London Imperial Coll Sci Technol & Med, London, England.
[Wang, Chia-Yih] Ctr Dis Control & Prevent, Hyattsville, MD USA.
[Rhodes, Donna G.] USDA, Beltsville, MD 20705 USA.
[Loria, Catherine M.] NIH, Bethesda, MD 20892 USA.
RP Cogswell, ME (reprint author), Ctr Dis Control & Prevent, Atlanta, GA 30333 USA.
EM mcogswell@cdc.gov
FU ASN; U.S. Department of Health and Human Services; USDA; CDC
[200-2010-43842]; National Institute for Health Research (NIHR)
Biomedical Research Centre at Imperial College Healthcare National
Health Service (NHS) Trust and Imperial College
FX This article is a summary of the symposium "Assessing U.S. Sodium Intake
Through Dietary Data and Urine Biomarkers" held April 24, 2013 at the
ASN Scientific Sessions and Annual Meeting at Experimental Biology 2013
in Boson, MA. The symposium was sponsored by the ASN and endorsed by ASN
the Medical Nutrition Council.; Supported by the U.S. Department of
Health and Human Services and USDA. Dr. Elliot's work supported by CDC
contract no. 200-2010-43842. Dr. Elliott also acknowledges support from
the National Institute for Health Research (NIHR) Biomedical Research
Centre at Imperial College Healthcare National Health Service (NHS)
Trust and Imperial College. He is an NIHR Senior Investigator. The
findings and conclusions in this report are those of the authors and do
not necessarily represent the official position of the CDC nor those of
the NHS, the NIHR or the Department of Health, UK.
NR 5
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PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 2161-8313
EI 2156-5376
J9 ADV NUTR
JI Adv. Nutr.
PD SEP
PY 2013
VL 4
IS 5
BP 560
EP 562
DI 10.3945/an.113.004309
PG 3
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 217KH
UT WOS:000324357900017
PM 24038257
ER
PT J
AU Zachwieja, J
Hentges, E
Hill, JO
Black, R
Vassileva, M
AF Zachwieja, Jeffrey
Hentges, Eric
Hill, James O.
Black, Richard
Vassileva, Maria
TI Public-Private Partnerships: The Evolving Role of Industry Funding in
Nutrition Research
SO ADVANCES IN NUTRITION
LA English
DT Editorial Material
AB The global burdens of morbidity and mortality associated with obesity-related chronic diseases are crippling public health and are predicted to exponentially increase over the next 3 decades. Meanwhile, the resources necessary to conduct research that may offer solutions to the obesity epidemic continue to decline and funding has become increasingly difficult to secure. Alternative models for funding nutrition and health research are necessary to make considerable and timely progress to improve public health. Key stakeholders include, but are not limited to, government agencies, foundations, private industry, and nongovernmental organizations.
C1 [Zachwieja, Jeffrey] Dairy Res Inst, Rosemont, IL USA.
[Hentges, Eric] Int Life Sci Inst North Amer, Washington, DC USA.
[Hill, James O.] Univ Colorado, Anschutz Hlth & Wellness Ctr, Boulder, CO 80309 USA.
[Black, Richard] PepsiCo Global Nutr, Purchase, NY USA.
[Vassileva, Maria] Fdn Natl Inst Hlth, Bethesda, MD USA.
RP Zachwieja, J (reprint author), Dairy Res Inst, Rosemont, IL USA.
FU ASN; Dairy Research Institute
FX This article is a summary of the symposium, "Public-Private
Partnerships: The Evolving Role of Industry Funding in Nutrition
Research" held April 23, 2013 at the American Society for Nutrition
Scientific Sessions and Annual Meeting held in conjunction with
Experimental Biology 2013 in Boston, MA. The symposium was sponsored by
the ASN and an educational grant from the Dairy Research Institute.
NR 1
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U2 16
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 2161-8313
EI 2156-5376
J9 ADV NUTR
JI Adv. Nutr.
PD SEP
PY 2013
VL 4
IS 5
BP 570
EP 572
DI 10.3945/an.113.004382
PG 3
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 217KH
UT WOS:000324357900021
PM 24038261
ER
PT J
AU Ohlhorst, SD
Russell, R
Bier, D
Klurfeld, DM
Li, ZP
Mein, JR
Milner, J
Ross, AC
Stover, P
Konopka, E
AF Ohlhorst, Sarah D.
Russell, Robert
Bier, Dennis
Klurfeld, David M.
Li, Zhaoping
Mein, Jonathan R.
Milner, John
Ross, A. Catharine
Stover, Patrick
Konopka, Emily
TI Nutrition research to affect food and a healthy lifespan
SO ADVANCES IN NUTRITION
LA English
DT Article
ID MEDITERRANEAN DIET; CHILDREN
AB Proper nutrition offers one of the most effective and least costly ways to decrease the burden of many diseases and their associated risk factors, including obesity. Nutrition research holds the key to increasing our understanding of the causes of obesity and its related comorbidities and thus holds promise to markedly influence global health and economies. After outreach to 75 thought leaders, the American Society for Nutrition (ASN) convened a Working Group to identify the nutrition research needs whose advancement will have the greatest projected impact on the future health and well-being of global populations. ASN's Nutrition Research Needs focus on the following high priority areas: 1) variability in individual responses to diet and foods; 2) healthy growth, development, and reproduction; 3) health maintenance; 4) medical management; 5) nutrition-related behaviors; and 6) food supply/environment. ASN hopes the Nutrition Research Needs will prompt collaboration among scientists across all disciplines to advance this challenging research agenda given the high potential for translation and impact on public health. Furthermore, ASN hopes the findings from the Nutrition Research Needs will stimulate the development and adoption of new and innovative strategies that can be applied toward the prevention and treatment of nutrition-related diseases. The multidisciplinary nature of nutrition research requires stakeholders with differing areas of expertise to collaborate on multifaceted approaches to establish the evidence-based nutrition guidance and policies that will lead to better health for the, global population. In addition to the identified research needs, ASN also identified 5 tools that are critical to the advancement of the Nutrition Research Needs: 1) omics, 2) bioinformatics, 3) databases, 4) biomarkers, and 5) cost-effectiveness analysis.
C1 [Ohlhorst, Sarah D.; Konopka, Emily] Amer Soc Nutr, Bethesda, MD 20814 USA.
[Russell, Robert] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
[Russell, Robert] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[Bier, Dennis] Baylor Coll Med, Childrens Nutr Res Ctr, USDA ARS, Dept Pediat, Houston, TX 77030 USA.
[Klurfeld, David M.] USDA ARS, Human Nutr Program, Beltsville, MD USA.
[Li, Zhaoping] Univ Calif Los Angeles, Ctr Human Nutr, Los Angeles, CA USA.
[Li, Zhaoping] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Mein, Jonathan R.] Monsanto Vegetable Seed, Monsanto Ctr Food & Nutr Res, Kannapolis, NC USA.
[Milner, John] NCI, NIH, Bethesda, MD 20892 USA.
[Ross, A. Catharine] Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA.
[Stover, Patrick] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA.
[Konopka, Emily] Nazareth Coll, Rochester, NY USA.
RP Ohlhorst, SD (reprint author), Amer Soc Nutr, 9650 Rockville Pike, Bethesda, MD 20814 USA.
EM sohlhorst@nutrition.org
NR 12
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U1 0
U2 16
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 2161-8313
J9 ADV NUTR
JI Adv. Nutr.
PD SEP
PY 2013
VL 4
IS 5
BP 579
EP 584
DI 10.3945/an.113004176
PG 6
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 217KH
UT WOS:000324357900025
PM 24038264
ER
PT J
AU Geda, YE
Schneider, LS
Gitlin, LN
Miller, DS
Smith, GS
Bell, J
Evans, J
Lee, M
Porsteinsson, A
Lanctot, KL
Rosenberg, PB
Sultzer, DL
Francis, PT
Brodaty, H
Padala, PP
Onyike, CU
Ortiz, LA
Ancoli-Israel, S
Bliwise, DL
Martin, JL
Vitiello, MV
Yaffe, K
Zee, PC
Herrmann, N
Sweet, RA
Ballard, C
Khin, NA
Alfaro, C
Murray, PS
Schultz, S
Lyketsos, CG
AF Geda, Yonas E.
Schneider, Lon S.
Gitlin, Laura N.
Miller, David S.
Smith, Gwenn S.
Bell, Joanne
Evans, Jovier
Lee, Michael
Porsteinsson, Anton
Lanctot, Krista L.
Rosenberg, Paul B.
Sultzer, David L.
Francis, Paul T.
Brodaty, Henry
Padala, Prasad P.
Onyike, Chiadikaobi U.
Ortiz, Luis Agueera
Ancoli-Israel, Sonia
Bliwise, Donald L.
Martin, Jennifer L.
Vitiello, Michael V.
Yaffe, Kristine
Zee, Phyllis C.
Herrmann, Nathan
Sweet, Robert A.
Ballard, Clive
Khin, Ni A.
Alfaro, Cara
Murray, Patrick S.
Schultz, Susan
Lyketsos, Constantine G.
CA Neuropsychiat Syndromes
TI Neuropsychiatric symptoms in Alzheimer's disease: Past progress and
anticipation of the future
SO ALZHEIMERS & DEMENTIA
LA English
DT Article
DE Neuropsychiatric symptoms; Behavioral and psychological symptoms of
dementia; Agitation/aggression; Sleep disorders; Depression; Apathy;
Psychosis; Delusions; Hallucinations; Dementia; Alzheimer's disease;
Mild cognitive impairment; Mild behavioral impairment
ID MILD COGNITIVE IMPAIRMENT; VASCULAR DEPRESSION HYPOTHESIS; PITTSBURGH
COMPOUND-B; ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; BEHAVIORAL
SYMPTOMS; NATIONAL INSTITUTE; RANDOMIZED-TRIAL; RATING-SCALE;
DOUBLE-BLIND
AB Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) are widespread and disabling. This has been known since Dr. Alois Alzheimer's first case, Frau Auguste D., presented with emotional distress and delusions of infidelity/excessive jealousy, followed by cognitive symptoms. Being cognizant of this, in 2010 the Alzheimer's Association convened a research roundtable on the topic of NPS in AD. A major outcome of the roundtable was the founding of a Professional Interest Area (PIA) within the International Society to Advance Alzheimer's Research and Treatment (ISTAART). The NPS-PIA has prepared a series of documents that are intended to summarize the literature and provide more detailed specific recommendations for NPS research. This overview paper is the first of these living documents that will be updated periodically as the science advances. The overview is followed by syndrome-specific synthetic reviews and recommendations prepared by NPS-PIA workgroups on depression, apathy, sleep, agitation, and psychosis. (C) 2013 The Alzheimer's Association. All rights reserved.
C1 [Geda, Yonas E.] Mayo Clin, Coll Med, Dept Psychiat, Scottsdale, AZ USA.
[Geda, Yonas E.] Mayo Clin, Coll Med, Dept Neurol, Scottsdale, AZ USA.
[Schneider, Lon S.] Univ So Calif, Los Angeles, CA USA.
[Gitlin, Laura N.] Johns Hopkins Univ, Sch Nursing, Baltimore, MD USA.
[Miller, David S.] Bracket, Wayne, PA USA.
[Smith, Gwenn S.; Rosenberg, Paul B.; Onyike, Chiadikaobi U.; Lyketsos, Constantine G.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Div Geriatr Psychiat & Neuropsychiat, Baltimore, MD 21218 USA.
[Evans, Jovier] NIMH, Geriatr Res Branch, Geriatr Translat Neurosci & MultiModal Interv Pro, Geriatr Pharmacol Intervent, Bethesda, MD 20892 USA.
[Lee, Michael] Univ Minnesota, Inst Translat Neurosci, Dept Neurosci, Minneapolis, MN USA.
[Lee, Michael] Univ Minnesota, Inst Translat Neurosci, Ctr Neurodegenerat Dis, Minneapolis, MN USA.
[Porsteinsson, Anton] Univ Rochester, Sch Med & Dent Rochester, Dept Psychiat, Rochester, NY USA.
[Lanctot, Krista L.] Sunnybrook Res Inst, Brain Sci Program, Toronto, ON, Canada.
[Lanctot, Krista L.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada.
[Lanctot, Krista L.] Univ Toronto, Dept Pharmacol, Toronto, ON, Canada.
[Lanctot, Krista L.] Univ Toronto, Dept Toxicol, Toronto, ON, Canada.
[Sultzer, David L.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, Los Angeles, CA 90024 USA.
[Sultzer, David L.] VA Greater Angeles Healthcare Syst, Psychiat Serv, Los Angeles, CA USA.
[Francis, Paul T.] Kings Coll London, Wolfson Ctr Age Related Dis, London, England.
[Brodaty, Henry] Univ New S Wales, Dementia Collaborat Res Ctr, Sydney, NSW, Australia.
[Padala, Prasad P.] Cent Arkansas Vet Healthcare Syst, Geriatr Res Educ & Clin Ctr, Little Rock, AR USA.
[Padala, Prasad P.] Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA.
[Ortiz, Luis Agueera] C1BERSAM, Madrid, Spain.
[Ortiz, Luis Agueera] Univ Hosp Doce Octubre, Madrid, Spain.
[Ancoli-Israel, Sonia] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
[Ancoli-Israel, Sonia] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
[Bliwise, Donald L.] Emory Univ, Sch Med, Wesley Woods Hlth Ctr, Dept Neurol, Atlanta, GA USA.
[Martin, Jennifer L.] Univ Calif Los Angeles, Educ & Clin Ctr, VA Greater Angeles Healthcare Geriatr Res, Los Angeles, CA USA.
[Martin, Jennifer L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Vitiello, Michael V.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
[Zee, Phyllis C.] Northwestern Univ, Feinberg Sch Med, Dept Neurol, Chicago, IL 60611 USA.
[Sweet, Robert A.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA.
[Sweet, Robert A.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA.
[Sweet, Robert A.; Murray, Patrick S.] VA Pittsburgh Healthcare Syst, VISN 4 Mental Illness Res Educ & Clin Ctr MIRECC, Pittsburgh, PA USA.
[Ballard, Clive] Kings Coll London, Wolfson Ctr Age Related Dis, Biomed Res Unit, Inst Psychiat & Alzheimers Soc, London WC2R 2LS, England.
[Khin, Ni A.; Alfaro, Cara] US FDA, Ctr Drug Evaluat & Res, Off Drug Evaluat 1 OND, Div Psychiat Prod, Silver Spring, MD USA.
[Schultz, Susan] Univ Iowa, Carver Coll Med, Dept Psychiat, Iowa City, IA USA.
RP Lyketsos, CG (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Div Geriatr Psychiat & Neuropsychiat, Baltimore, MD 21218 USA.
RI Lee, Michael/D-9491-2013; Francis, Paul/A-9199-2008;
OI Lee, Michael/0000-0001-5865-9682; Murray, Patrick/0000-0002-6525-2888;
Vitiello, Michael/0000-0002-9776-0473; Lanctot, Krista
L./0000-0001-7024-6637
FU NIMH [K01-MH68351, R24-MH074779, R01-MH079814, RC1-MH090770-01]; NIA
[U01-AG006786]; National Center for Research Resources [RR024150];
Robert Wood Johnson Foundation; European Union Regional Development Fund
[FNUSA-ICRC: CZ.1.05/1.1.00/02.0123]; Baxter; Elan Pharmaceuticals;
Johnson Johnson; Eli Lilly; Myriad; Novartis; Pfizer; Abbott
Laboratories; AC Immune; Allergan; Allon; Alzheimer Drug Discovery
Foundation; AstraZeneca; Bristol-Myers Squibb; Elan; Exonhit; Forest;
GlaxoSmithKline; Ipsen Pharmaceuticals; Lundbeck; Medavante; Medivation;
Merck; Merz; Roche; Sanofi-Aventis; Schering-Plough; Schwabe; Toyama;
Transition Therapeutics; Alzheimer's Association [IIRG-07-28686]; Johns
Hopkins Alzheimer's Disease Research Center [P50-AG005146]; NIMH, MA;
Associated Jewish Federation of Baltimore; Weinberg Foundation; Eisai;
Lilly; Ortho-McNeil; Bristol-Myers; National Football League; Functional
Neuromodulation Inc.
FX The authors thank Dr. Michelle M. Mielke for her helpful comments and
feedback on early drafts of this manuscript. Dr. Geda was supported by
NIMH grant K01-MH68351, NIA grant U01-AG006786 (the Mayo Clinic Study of
Aging), National Center for Research Resources grant RR024150 (Mayo
Clinic CTSA [Career Transition Award]), the Robert Wood Johnson
Foundation (Harold Amos Scholar), and the European Union Regional
Development Fund (Project FNUSA-ICRC: CZ.1.05/1.1.00/02.0123). Dr.
Schneider reports being an editor on the Cochrane Collaboration Dementia
and Cognitive Improvement Group, which oversees systematic reviews of
drugs for cognitive impairment and dementia. He received a grant from
the Alzheimer's Association for a registry for dementia and cognitive
impairment trials; he is also in receipt of grant or research support
from Baxter, Elan Pharmaceuticals, Johnson & Johnson, Eli Lilly, Myriad,
Novartis, and Pfizer. He has served as a consultant for or received
consulting fees from Abbott Laboratories, AC Immune, Allergan, Allon,
the Alzheimer Drug Discovery Foundation, AstraZeneca, Bristol-Myers
Squibb, Elan, Eli Lilly, Exonhit, Forest, GlaxoSmithKline, Ipsen
Pharmaceuticals, Johnson & Johnson, Lundbeck, Myriad, Medavante,
Medivation, Merck, Merz, Novartis, Pfizer, Roche, Sanofi-Aventis,
Schering-Plough, Schwabe, Toyama, and Transition Therapeutics. Dr.
Gitlin was supported by NIMH grants R24-MH074779, R01-MH079814, and
RC1-MH090770-01 and Alzheimer's Association grant IIRG-07-28686 and
served on the Phillips Life Line Falls Advisory Board. Dr. Miller is a
full-time employee of Bracket. Dr. Lyketsos was supported by the Johns
Hopkins Alzheimer's Disease Research Center (P50-AG005146). He has
received grant support (research or CME) from NIMH, MA, the Associated
Jewish Federation of Baltimore, the Weinberg Foundation, Forest,
GlaxoSmithKline, Eisai, Pfizer, AstraZeneca, Lilly, Ortho-McNeil,
Bristol-Myers, Novartis, the National Football League, Elan, and
Functional Neuromodulation Inc. He has served as consultant/advisor for
AstraZeneca, GlaxoSmithKline, Eisai, Novartis, Forest, Supernus, Adlyfe,
Takeda, Wyeth, Lundbeck, Merz, Lilly, Pfizer, Genentech, Elan, the NFL
Players Association, the NFL Benefits Office, Avanir, and Zinfandel. He
has also received honorarium or travel support from Pfizer, Forest,
GlaxoSmithKline, and Health Monitor.
NR 68
TC 75
Z9 76
U1 8
U2 43
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1552-5260
J9 ALZHEIMERS DEMENT
JI Alzheimers. Dement.
PD SEP
PY 2013
VL 9
IS 5
BP 602
EP 608
DI 10.1016/j.jalz.2012.12.001
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 222IN
UT WOS:000324724500015
PM 23562430
ER
PT J
AU Whirledge, S
Xu, XJ
Cidlowski, JA
AF Whirledge, Shannon
Xu, Xiaojiang
Cidlowski, John A.
TI Global Gene Expression Analysis in Human Uterine Epithelial Cells
Defines New Targets of Glucocorticoid and Estradiol Antagonism
SO BIOLOGY OF REPRODUCTION
LA English
DT Article
DE epithelial cells; ESR1; estrogen receptor; glucocorticoid receptor;
microarray; NR3C1; uterus
ID STIMULATING-HORMONE RECEPTOR; FEMALE REPRODUCTIVE-TRACT; FACTOR-BINDING
PROFILES; OPEN-ACCESS DATABASE; TRANSCRIPTION FACTOR; EMBRYO
IMPLANTATION; STROMAL CELLS; INFLAMMATORY RESPONSE; MICROARRAY ANALYSIS;
MOUSE UTERUS
AB In preparation for embryo implantation and pregnancy, the uterine epithelium undergoes a genomic and biological transition that mediates adhesion and invasion of the blastocyst. These events resemble an inflammatory response, and the immune system likely takes an active role in the establishment and maintenance of pregnancy. Although glucocorticoids are primary mediators of the immune system, the functional role of glucocorticoid signaling in the uterine epithelium is not well defined. To investigate the dynamic relationship between glucocorticoids and reproductive hormones, we performed whole-genome microarray analysis in a human uterine endometrial cancer cell line (ECC1 cells) treated with the synthetic glucocorticoid dexamethasone (Dex) alone or in combination with estradiol (E-2). Over 10 000 genes were significantly regulated in the presence of Dex and/or E-2. Surprisingly, unique targets of Dex and E-2 together represented the largest group of regulated genes. Ingenuity pathway analysis found both overlapping and independent regulated networks for each hormone. Several hundred genes were found to be coregulated by Dex and E-2, including several that were antagonistically regulated. The effects of glucocorticoids and E-2 are mediated primarily through the glucocorticoid receptor (NR3C1) and estrogen receptor (ESR1), respectively. In silico promoter analysis revealed that NR3C1 and ESR1 response elements are enriched in antagonistically regulated genes, and signaling through these receptors was required for antagonism. Glucocorticoid and E-2 antagonism of target genes may represent a critical junction between the immune system and female reproductive system. Moreover, identification and ontology analysis of glucocorticoid-regulated genes in a uterine epithelial-like cell line suggests that glucocorticoid signaling regulates important biological functions, including immune cell trafficking and embryonic development.
C1 [Whirledge, Shannon; Cidlowski, John A.] NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Xu, Xiaojiang] NIEHS, Lab Integrat Bioinformat, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Cidlowski, JA (reprint author), NIEHS, NIH, MD F3-07,POB 12233, Res Triangle Pk, NC 27709 USA.
EM cidlows1@niehs.nih.gov
FU Intramural Research Program of the NIH National Institute of
Environmental Health Sciences
FX Supported by the Intramural Research Program of the NIH National
Institute of Environmental Health Sciences.
NR 75
TC 12
Z9 12
U1 0
U2 2
PU SOC STUDY REPRODUCTION
PI MADISON
PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA
SN 0006-3363
J9 BIOL REPROD
JI Biol. Reprod.
PD SEP
PY 2013
VL 89
IS 3
AR 66
DI 10.1095/biolreprod.113.111054
PG 17
WC Reproductive Biology
SC Reproductive Biology
GA 226AS
UT WOS:000325007200017
PM 23843231
ER
PT J
AU FitzGerald, LM
Kumar, A
Boyle, EA
Zhang, YZ
McIntosh, LM
Kolb, S
Stott-Miller, M
Smith, T
Karyadi, DM
Ostrander, EA
Hsu, L
Shendure, J
Stanford, JL
AF FitzGerald, Liesel M.
Kumar, Akash
Boyle, Evan A.
Zhang, Yuzheng
McIntosh, Laura M.
Kolb, Suzanne
Stott-Miller, Marni
Smith, Tiffany
Karyadi, Danielle M.
Ostrander, Elaine A.
Hsu, Li
Shendure, Jay
Stanford, Janet L.
TI Germline Missense Variants in the BTNL2 Gene Are Associated with
Prostate Cancer Susceptibility
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID AUTISM SPECTRUM DISORDERS; BRCA2 GENE; MUTATIONS; HOXB13; RISK; LOCI;
SEQUENCE; IDENTIFICATION; INFLAMMATION; SARCOIDOSIS
AB Background: Rare, inherited mutations account for 5% to 10% of all prostate cancer cases. However, to date, few causative mutations have been identified.
Methods: To identify rare mutations for prostate cancer, we conducted whole-exome sequencing (WES) in multiple kindreds (n = 91) from 19 hereditary prostate cancer (HPC) families characterized by aggressive or early-onset phenotypes. Candidate variants (n = 130) identified through family- and bioinformatics-based filtering of WES data were then genotyped in an independent set of 270 HPC families (n = 819 prostate cancer cases; n = 496 unaffected relatives) for replication. Two variants with supportive evidence were subsequently genotyped in a population-based case-control study (n = 1,155 incident prostate cancer cases; n = 1,060 age-matched controls) for further confirmation. All participants were men of European ancestry.
Results: The strongest evidence was for two germline missense variants in the butyrophilin-like 2 (BTNL2) gene (rs41441651, p. Asp336Asn and rs28362675, p.Gly454Cys) that segregated with affection status in two of the WES families. In the independent set of 270 HPC families, 1.5% (rs41441651; P = 0.0032) and 1.2% (rs28362675; P = 0.0070) of affected men, but no unaffected men, carried a variant. Both variants were associated with elevated prostate cancer risk in the population-based study (rs41441651: OR, 2.7; 95% CI, 1.27-5.87; P = 0.010; rs28362675: OR, 2.5; 95% CI, 1.16-5.46; P = 0.019).
Conclusions: Results indicate that rare BTNL2 variants play a role in susceptibility to both familial and sporadic prostate cancer.
Impact: Results implicate BTNL2 as a novel prostate cancer susceptibility gene. (C) 2013 AACR.
C1 [FitzGerald, Liesel M.; Zhang, Yuzheng; McIntosh, Laura M.; Kolb, Suzanne; Stott-Miller, Marni; Hsu, Li; Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Kumar, Akash; Boyle, Evan A.; Shendure, Jay] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA USA.
[Stanford, Janet L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
[Smith, Tiffany; Karyadi, Danielle M.; Ostrander, Elaine A.] NHGRI, NIH, Canc Genet Branch, Bethesda, MD 20892 USA.
RP Stanford, JL (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,POB 19024,M4-B874, Seattle, WA 98109 USA.
EM jstanfor@fhcrc.org
OI Boyle, Evan/0000-0003-4494-9771; Shendure, Jay/0000-0002-1516-1865;
Ostrander, Elaine/0000-0001-6075-9738
FU U.S. National Cancer Institute, NIH [RO1 CA080122, P50 CA097186]; Fred
Hutchinson Cancer Research Center; Prostate Cancer Foundation; NIH
[HHSN268200782096C]; NHLBI [RC2 HL-103010, RC2 HL-102923, RC2 HL-102924,
RC2 HL-102925, RC2 HL-102926]; Achievement Award for College Scientists
Fellowship; Lowell Milken Prostate Cancer Foundation Young Investigator
Award; Intramural Program of the National Human Genome Research
Institute; Prostate Cancer Foundation Creativity Award
FX This work was supported by grants from the U.S. National Cancer
Institute, NIH (grant numbers RO1 CA080122 and P50 CA097186 to J.L.
Stanford); with additional support from the Fred Hutchinson Cancer
Research Center; and the Prostate Cancer Foundation. Sequencing services
were provided by the Center for Inherited Disease Research, which is
funded through a contract from NIH to The Johns Hopkins University
(contract no. HHSN268200782096C). Funding for GO ESP was provided by
NHLBI grants RC2 HL-103010 (HeartGO), RC2 HL-102923 (LungGO), and RC2
HL-102924 (WHISP). The exome sequencing was conducted through NHLBI
grants RC2 HL-102925 (BroadGO) and RC2 HL-102926 (SeattleGO). A. Kumar
is supported by an Achievement Award for College Scientists Fellowship;
J. Shendure is supported by The Lowell Milken Prostate Cancer Foundation
Young Investigator Award; E. A. Ostrander is supported by the Intramural
Program of the National Human Genome Research Institute; J. L. Stanford
is supported by a Prostate Cancer Foundation Creativity Award.
NR 47
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Z9 12
U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD SEP
PY 2013
VL 22
IS 9
BP 1520
EP 1528
DI 10.1158/1055-9965.EPI-13-0345
PG 9
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 221QV
UT WOS:000324674500005
PM 23833122
ER
PT J
AU Karami, S
Andreotti, G
Koutros, S
Barry, KH
Moore, LE
Han, S
Hoppin, JA
Sandler, DP
Lubin, JH
Burdette, LA
Yuenger, J
Yeager, M
Freeman, LEB
Blair, A
Alavanja, MCR
AF Karami, Sara
Andreotti, Gabriella
Koutros, Stella
Barry, Kathryn Hughes
Moore, Lee E.
Han, Summer
Hoppin, Jane A.
Sandler, Dale P.
Lubin, Jay H.
Burdette, Laurie A.
Yuenger, Jeffrey
Yeager, Meredith
Freeman, Laura E. Beane
Blair, Aaron
Alavanja, Michael C. R.
TI Pesticide Exposure and Inherited Variants in Vitamin D Pathway Genes in
Relation to Prostate Cancer
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; NON-HODGKINS-LYMPHOMA; AGRICULTURAL HEALTH; SUN
EXPOSURE; RISK-FACTORS; APPLICATORS; PREVENTION; RECEPTOR;
POLYMORPHISMS; RADIATION
AB Background: Vitamin D and its metabolites are believed to impede carcinogenesis by stimulating cell differentiation, inhibiting cell proliferation, and inducing apoptosis. Certain pesticides have been shown to deregulate vitamin D's anticarcinogenic properties. We hypothesize that certain pesticides may be linked to prostate cancer via an interaction with vitamin D genetic variants.
Methods: We evaluated interactions between 41 pesticides and 152 single-nucleotide polymorphisms (SNP) in nine vitamin D pathway genes among 776 prostate cancer cases and 1,444 male controls in a nested case-control study of Caucasian pesticide applicators within the Agricultural Health Study. We assessed P-interaction values using likelihood ratio tests from unconditional logistic regression and a false discovery rate (FDR) to account for multiple comparisons.
Results: Five significant interactions (P < 0.01) displayed a monotonic increase in prostate cancer risk with individual pesticide use in one genotype and no association in the other. These interactions involved parathion and terbufos use and three vitamin D genes (VDR, RXRB, and GC). The exposure-response pattern among participants with increasing parathion use with the homozygous CC genotype for GC rs7041 compared with unexposed participants was noteworthy [low vs. no exposure: OR, 2.58, 95% confidence interval (CI), 1.07-6.25; high vs. no exposure: OR, 3.09, 95% CI, 1.10-8.68; P-interaction = 3.8 x 10(-3)].
Conclusions: In this study, genetic variations in vitamin D pathway genes, particularly GC rs7041, an SNP previously linked to lower circulating vitamin D levels, modified pesticide associations with prostate cancer risk.
Impact: Because our study is the first to examine this relationship, additional studies are needed to rule out chance findings. (C) 2013 AACR.
C1 [Karami, Sara; Andreotti, Gabriella; Koutros, Stella; Barry, Kathryn Hughes; Moore, Lee E.; Han, Summer; Lubin, Jay H.; Freeman, Laura E. Beane; Blair, Aaron; Alavanja, Michael C. R.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
[Burdette, Laurie A.; Yuenger, Jeffrey; Yeager, Meredith] SAIC Frederick Inc, Natl Canc Inst Frederick, Core Genotyping Facil, Frederick, MD USA.
[Hoppin, Jane A.; Sandler, Dale P.] NIH, Epidemiol Branch, Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
RP Karami, S (reprint author), NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, 6120 Execut Blvd,EPS 8121, Rockville, MD 20852 USA.
EM karamis@mail.nih.gov
OI Sandler, Dale/0000-0002-6776-0018
FU Intramural Research Program of the NCI, Division of Cancer Epidemiology
and Genetics [Z01CP010119]; National Institute of Environmental Health
Sciences (NIEHS), NIH [Z01ES049030]
FX This research was supported by the Intramural Research Program of the
NCI, Division of Cancer Epidemiology and Genetics (Z01CP010119) and the
National Institute of Environmental Health Sciences (NIEHS;
Z01ES049030), NIH.
NR 63
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Z9 8
U1 1
U2 18
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD SEP
PY 2013
VL 22
IS 9
BP 1557
EP 1566
DI 10.1158/1055-9965.EPI-12-1454
PG 10
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 221QV
UT WOS:000324674500009
PM 23833127
ER
PT J
AU Andreotti, G
Birmann, B
De Roos, AJ
Spinelli, J
Cozen, W
Camp, NJ
Moysich, K
Chiu, B
Steplowski, E
Krzystan, J
Boffetta, P
Benhaim-Luzon, V
Brennan, P
de Sanjose, S
Costas, L
Costantini, AS
Miligi, L
Cocco, P
Becker, N
Foretova, L
Maynadie, M
Nieters, A
Staines, A
Tricot, G
Milliken, K
Weisenburger, D
Zheng, TZ
Baris, D
Purdue, MP
AF Andreotti, Gabriella
Birmann, Brenda
De Roos, Anneclaire J.
Spinelli, John
Cozen, Wendy
Camp, Nicola J.
Moysich, Kirsten
Chiu, Brian
Steplowski, Emily
Krzystan, Joseph
Boffetta, Paolo
Benhaim-Luzon, Veronique
Brennan, Paul
de Sanjose, Silvia
Costas, Laura
Costantini, Adele Seniori
Miligi, Lucia
Cocco, Pierluigi
Becker, Nikolaus
Foretova, Lenka
Maynadie, Marc
Nieters, Alexandra
Staines, Anthony
Tricot, Guido
Milliken, Kevin
Weisenburger, Dennis
Zheng, Tongzhang
Baris, Dalsu
Purdue, Mark P.
TI A Pooled Analysis of Alcohol Consumption and Risk of Multiple Myeloma in
the International Multiple Myeloma Consortium
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID NON-HODGKIN-LYMPHOMA; CONNECTICUT WOMEN; CIGARETTE-SMOKING; COHORT;
DIET; NEOPLASMS; BEVERAGES; DRINKING; TOBACCO; CELLS
AB Background: Recent findings suggest that alcohol consumption may reduce risk of multiple myeloma.
Methods: To better understand this relationship, we conducted an analysis of six case-control studies participating in the International Multiple Myeloma Consortium (1,567 cases, 7,296 controls). Summary ORs and 95% confidence intervals (CI) relating different measures of alcohol consumption and multiple myeloma risk were computed by unconditional logistic regression with adjustment for age, race, and study center.
Results: Cases were significantly less likely than controls to report ever drinking alcohol (men: OR = 0.72; 95% CI, 0.59-0.89; women: OR = 0.81; 95% CI, 0.68-0.95). The inverse association with multiple myeloma was stronger when comparing current to never drinkers (men: OR = 0.57; 95% CI, 0.45-0.72; women: OR = 0.55; 95% CI, 0.45-0.68), but null among former drinkers. We did not observe an exposure-response relationship with increasing alcohol frequency, duration, or cumulative lifetime consumption. Additional adjustment for body mass index, education, or smoking did not affect our results; and the patterns of association were similar for each type of alcohol beverage examined.
Conclusions: Our study is, to our knowledge, the largest of its kind to date, and our findings suggest that alcohol consumption may be associated with reduced risk of multiple myeloma.
Impact: Prospective studies, especially those conducted as pooled analyses with large sample sizes, are needed to confirm our findings and further explore whether alcohol consumption provides true biologic protection against this rare, highly fatal malignancy. (C) 2013 AACR.
C1 [Andreotti, Gabriella; Baris, Dalsu; Purdue, Mark P.] NIH, DHHS, Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Steplowski, Emily; Krzystan, Joseph] Informat Management Serv Inc, Silver Spring, MD USA.
[Birmann, Brenda] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[Birmann, Brenda] Harvard Med Sch, Boston, MA USA.
[De Roos, Anneclaire J.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Spinelli, John] Univ British Columbia, BC Canc Agcy, Vancouver, BC V5Z 1M9, Canada.
[Spinelli, John] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC V5Z 1M9, Canada.
[Cozen, Wendy] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Cozen, Wendy] Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Camp, Nicola J.] Univ Utah, Sch Med, Div Genet Epidemiol, Salt Lake City, UT USA.
[Moysich, Kirsten] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[Boffetta, Paolo] Mt Sinai Sch Med, New York, NY USA.
[Chiu, Brian] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA.
[Tricot, Guido] Univ Iowa, Dept Internal Med, Iowa City, IA USA.
[Weisenburger, Dennis] Univ Nebraska, Med Ctr, Pathol & Microbiol Dept, Lincoln, NE USA.
[Zheng, Tongzhang] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA.
[Boffetta, Paolo] Int Prevent Res Inst, Lyon, France.
[Benhaim-Luzon, Veronique; Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France.
[Maynadie, Marc] Univ Burgundy, Registry Hematol Malignanc Cote, EA4184, Dijon, France.
[de Sanjose, Silvia; Costas, Laura] Univ Barcelona, IDIBELL, Catalan Inst Oncol, Unit Infect & Canc, Barcelona, Spain.
[Costas, Laura] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada.
[Costantini, Adele Seniori; Miligi, Lucia] Ctr Study & Prevent Canc, Unit Occupat & Environm Epidemiol, Florence, Italy.
[Cocco, Pierluigi] Univ Cagliari, Dept Publ Hlth, Occupat Hlth Sect, Cagliari, Italy.
[Becker, Nikolaus] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Nieters, Alexandra] German Canc Res Ctr, Div Clin Epidemiol, Heidelberg, Germany.
[Foretova, Lenka] Masaryk Mem Canc Inst, Dep Canc Epidemiol & Genet, Brno, Czech Republic.
[Staines, Anthony] Publ Hlth Univ Coll, Dept Publ Hlth, Dublin, Ireland.
RP Andreotti, G (reprint author), Natl Canc Inst, Med Ctr 6909, Dr Rm 6E622,MSC 9704, Bethesda, MD 20892 USA.
EM andreotg@mail.nih.gov
RI Spinelli, John/B-6210-2013; de Sanjose Llongueras, Silvia/H-6339-2014;
Purdue, Mark/C-9228-2016;
OI Purdue, Mark/0000-0003-1177-3108; Costas, Laura/0000-0003-2755-302X;
Staines, Anthony/0000-0001-9161-1357
FU Leukemia and Lymphoma Society [6067-09]; NCI [CA152336, P30 CA42014, K07
CA115687, CA149445]; HCI Cancer Center; NCI SEER [HHSN261201000026C];
Utah State Department of Health; University of Utah; European Regional
Development Fund; State Budget of the Czech Republic (RECAMO)
[CZ.1.05/2.1.00/03.0101]; American Cancer Society [RSG-11-020-01-CNE]
FX Funding for the Utah study was in part from the Leukemia and Lymphoma
Society 6067-09 (N.J. Camp) and the NCI CA152336 (N.J. Camp). Data
collection for the Utah resource was made possible by the Utah
Population Database (UPDB) and the Utah Cancer Registry (UCR). Partial
support for all datasets within the UPDB was provided by the University
of Utah Huntsman Cancer Institute (HCI) and the HCI Cancer Center
Support grant, P30 CA42014 from the NCI. The UCR is funded by contract
HHSN261201000026C from the NCI SEER program with additional support from
the Utah State Department of Health and the University of Utah. The work
was supported by the European Regional Development Fund and the State
Budget of the Czech Republic (RECAMO, CZ.1.05/2.1.00/03.0101). The work
conducted by B. Birmann was supported in part by grants from the NCI
(K07 CA115687, CA149445) and the American Cancer Society
(RSG-11-020-01-CNE).
NR 28
TC 6
Z9 6
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD SEP
PY 2013
VL 22
IS 9
BP 1620
EP 1627
DI 10.1158/1055-9965.EPI-13-0334
PG 8
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 221QV
UT WOS:000324674500015
PM 23964064
ER
PT J
AU Wernli, KJ
Kitahara, CM
Tamers, SL
Al-Temimi, MH
Braithwaite, D
AF Wernli, Karen J.
Kitahara, Cari M.
Tamers, Sara L.
Al-Temimi, Mohammed H.
Braithwaite, Dejana
TI Undertaking Cancer Research in International Settings: Report from the
American Society for Preventive Oncology Special Interest Group on
International Issues in Cancer
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID HEALTH RECORDS REGISTER; STRESSFUL LIFE EVENTS; COHORT PROFILE; ALCOHOL;
HEIGHT
AB The mission of the American Society for Preventive Oncology Special Interest Group in International Issues in Cancer is to serve as a worldwide cancer prevention resource. At the 2013 annual meeting, we presented three early career investigators who conducted research with international collaborators as part of postdoctoral studies. We present a synopsis of each of the scientific presentations. The investigators also highlight useful strategies to encourage a more successful international collaboration, including seeking out existing collaborations between colleagues and international researchers, maintaining awareness and sensitivity of cultural norms, establishing clear communication about investigator roles and expectations, and persevering in the face of potential challenges due to the nature of these collaborations. Incorporation of these key elements could prove useful for researchers interested in pursuing cross-country projects. (C) 2013 AACR.
C1 [Wernli, Karen J.] Grp Hlth Res Inst, Seattle, WA USA.
[Kitahara, Cari M.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Tamers, Sara L.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA.
[Tamers, Sara L.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA.
[Al-Temimi, Mohammed H.] Univ Utah, Dept Family & Prevent Med, Div Publ Hlth, Salt Lake City, UT USA.
[Braithwaite, Dejana] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94107 USA.
RP Braithwaite, D (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, 185 Berry St,Suite 5700, San Francisco, CA 94107 USA.
EM DBraithwaite@epi.ucsf.edu
RI Kitahara, Cari/R-8267-2016
FU Agency for Healthcare Research and Quality K12 Comparative Effectiveness
Research Scholar Award [K12 HS019482]; Intramural Research Program of
the National Cancer Institute (NCI), NIH; NIH/NCI Harvard Education
Program in Cancer Prevention and Control [R25 CA057713]; NIH/NCI
Reducing Social Disparities in Cancer Risk [K05 CA108663-05]; European
Commission Public Health Programme, DG Sanco [2006 319]; American Cancer
Society [121891-MRSG-12-007-01-CPHPS]
FX K.J. Wernli was supported in part by Agency for Healthcare Research and
Quality K12 Comparative Effectiveness Research Scholar Award (K12
HS019482). C. M. Kitahara was supported in part by the Intramural
Research Program of the National Cancer Institute (NCI), NIH. S. L.
Tamers was supported in part by the NIH/NCI Harvard Education Program in
Cancer Prevention and Control (R25 CA057713; PI G. Sorensen), and the
NIH/NCI Reducing Social Disparities in Cancer Risk (K05 CA108663-05 to
GS). The work of M. H. Al-Temimi was part of the Women in Europe against
Lung Cancer and Smoking (WELAS) project, which was supported by the
European Commission Public Health Programme, DG Sanco (Grant # 2006
319). D. Braithwaite was supported in part by Grant #
121891-MRSG-12-007-01-CPHPS from the American Cancer Society.
NR 20
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U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD SEP
PY 2013
VL 22
IS 9
BP 1638
EP 1641
DI 10.1158/1055-9965.EPI-13-0655
PG 4
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 221QV
UT WOS:000324674500019
PM 23845714
ER
PT J
AU Boudreaux, ED
Miller, I
Goldstein, AB
Sullivan, AF
Allen, MH
Manton, AP
Arias, SA
Camargo, CA
AF Boudreaux, Edwin D.
Miller, Ivan
Goldstein, Amy B.
Sullivan, Ashley F.
Allen, Michael H.
Manton, Anne P.
Arias, Sarah A.
Camargo, Carlos A., Jr.
TI The Emergency Department Safety Assessment and Follow-up Evaluation
(ED-SAFE): Method and design considerations
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Article
DE Suicide; Research methods; Mental health; Emergency department
ID SUICIDAL-BEHAVIOR; INTERVENTION RESEARCH; RISK; HEALTH; PREVALENCE;
THOUGHTS; FIREARMS; SYSTEM
AB Background: Due to the concentration of individuals at-risk for suicide, an emergency department visit represents an opportune time for suicide risk screening and intervention.
Purpose: The Emergency Department Safety Assessment and Follow-up Evaluation (ED-SAFE) uses a quasi-experimental, interrupted time series design to evaluate whether (1) a practical approach to universally screening ED patients for suicide risk leads to improved detection of suicide risk and (2) a multi-component intervention delivered during and after the ED visit improves suicide-related outcomes.
Methods: This paper summarizes the ED-SAFE's study design and methods within the context of considerations relevant to effectiveness research in suicide prevention and pertinent human participants concerns. 1440 suicidal individuals, from 8 general ED's nationally will be enrolled during three sequential phases of data collection (480 individuals/phase): (1) Treatment as Usual; (2) Universal Screening; and (3) Intervention. Data from the three phases will inform two separate evaluations: Screening Outcome (Phases 1 and 2) and Intervention (Phases 2 and 3). Individuals will be followed for 12 months. The primary study outcome is a composite reflecting completed suicide, attempted suicide, aborted or interrupted attempts, and implementation of rescue procedures during an outcome assessment.
Conclusions: While 'classic' randomized control trials (RCT) are typically selected over quasi-experimental designs, ethical and methodological issues may make an RCT a poor fit for complex interventions in an applied setting, such as the ED. ED-SAFE represents an innovative approach to examining the complex public health issue of suicide prevention through a multi-phase, quasi-experimental design embedded in 'real world' clinical settings. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Dept Emergency Med, Worcester, MA 01655 USA.
[Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA.
[Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Worcester, MA 01655 USA.
[Miller, Ivan] Butler Hosp, Providence, RI 02906 USA.
[Goldstein, Amy B.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA.
[Goldstein, Amy B.] NIMH, Div Serv & Intervent Res, NIH, Bethesda, MD 20892 USA.
[Sullivan, Ashley F.; Arias, Sarah A.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Allen, Michael H.] Univ Colorado, Depress Ctr, Aurora, CO USA.
[Allen, Michael H.] VISN 19 MIRECC, Aurora, CO USA.
[Manton, Anne P.] Cape Cod Hosp, Cape Psychiat Ctr, Cape Cod, MA USA.
RP Boudreaux, ED (reprint author), Univ Massachusetts, Sch Med, LA 189,55 Lake Ave North, Worcester, MA 01655 USA.
EM Edwin.Boudreaux@umassmed.edu
RI Allen, Michael/A-8776-2011;
OI Boudreaux, Edwin/0000-0002-3223-6371; Arias, Sarah/0000-0003-1832-8824
FU National Institute on Mental Health [U01MH088278]
FX The project described was supported by Award Number U01MH088278 from the
National Institute on Mental Health. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institute of Mental Health or the
National Institutes of Health. None of the authors have financial
conflicts of interest to disclose.
NR 26
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U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1551-7144
J9 CONTEMP CLIN TRIALS
JI Contemp. Clin. Trials
PD SEP
PY 2013
VL 36
IS 1
BP 14
EP 24
DI 10.1016/j.cct.2013.05.008
PG 11
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 225KH
UT WOS:000324961300002
PM 23707435
ER
PT J
AU Eastmond, DA
Vulimiri, SV
French, JE
Sonawane, B
AF Eastmond, David A.
Vulimiri, Suryanarayana V.
French, John E.
Sonawane, Babasaheb
TI The use of genetically modified mice in cancer risk assessment:
Challenges and limitations
SO CRITICAL REVIEWS IN TOXICOLOGY
LA English
DT Review
DE Carcinogen; concordance; dose-response; hazard identification;
mechanism; pathway-specificity; study duration; transgenic
ID TRANSGENIC MOUSE MODELS; HA-RAS GENE; SHORT-TERM CARCINOGENICITY;
CENTER-DOT-AC; WILD-TYPE P53; TG.AC MICE; IDENTIFYING CARCINOGENS;
CHEMICAL CARCINOGENESIS; COLLABORATIVE CROSS; ALTERNATIVE MODELS
AB The use of genetically modified (GM) mice to assess carcinogenicity is playing an increasingly important role in the safety evaluation of chemicals. While progress has been made in developing and evaluating mouse models such as the Trp53(+/-), Tg.AC and the rasH2, the suitability of these models as replacements for the conventional rodent cancer bioassay and for assessing human health risks remains uncertain. The objective of this research was to evaluate the use of accelerated cancer bioassays with GM mice for assessing the potential health risks associated with exposure to carcinogenic agents. We compared the published results from the GM bioassays to those obtained in the National Toxicology Program's conventional chronic mouse bioassay for their potential use in risk assessment. Our analysis indicates that the GM models are less efficient in detecting carcinogenic agents but more consistent in identifying non-carcinogenic agents. We identified several issues of concern related to the design of the accelerated bioassays (e.g., sample size, study duration, genetic stability and reproducibility) as well as pathway-dependency of effects, and different carcinogenic mechanisms operable in GM and non-GM mice. The use of the GM models for dose-response assessment is particularly problematic as these models are, at times, much more or less sensitive than the conventional rodent cancer bioassays. Thus, the existing GM mouse models may be useful for hazard identification, but will be of limited use for dose-response assessment. Hence, caution should be exercised when using GM mouse models to assess the carcinogenic risks of chemicals.
C1 [Eastmond, David A.] Univ Calif Riverside, Dept Cell Biol & Neurosci, Riverside, CA 92521 USA.
[Vulimiri, Suryanarayana V.; Sonawane, Babasaheb] US EPA, Natl Ctr Environm Assessment, Washington, DC 20460 USA.
[French, John E.] NIEHS, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
RP Eastmond, DA (reprint author), Univ Calif Riverside, Dept Cell Biol & Neurosci, Riverside, CA 92521 USA.
EM david.eastmond@ucr.edu
OI Vulimiri, Suryanarayana/0000-0003-3734-0036
FU Intramural NIH HHS [Z99 ES999999]
NR 140
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U1 0
U2 15
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1040-8444
EI 1547-6898
J9 CRIT REV TOXICOL
JI Crit. Rev. Toxicol.
PD SEP
PY 2013
VL 43
IS 8
BP 611
EP 631
DI 10.3109/10408444.2013.822844
PG 21
WC Toxicology
SC Toxicology
GA 219EV
UT WOS:000324489800001
PM 23985072
ER
PT J
AU Kennedy, AP
Epstein, DH
Phillips, KA
Preston, KL
AF Kennedy, Ashley P.
Epstein, David H.
Phillips, Karran A.
Preston, Kenzie L.
TI Sex differences in cocaine/heroin users: Drug-use triggers and craving
in daily life
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE Ecological momentary assessment; Sex differences; Craving; Cocaine;
Heroin; Drug cues; Gender; Methadone treatment
ID ECOLOGICAL MOMENTARY ASSESSMENT; SUBSTANCE-ABUSE TREATMENT;
GENDER-DIFFERENCES; DEPENDENT WOMEN; MENSTRUAL-CYCLE; SMOKED COCAINE;
HEROIN USERS; ADDICT CAREERS; ALCOHOL; MEN
AB Background: Studies of sex differences have shown that men and women with drug-use disorders differ in course and outcome and in cue-induced activation of putative brain "control network" areas. We evaluated sex differences in daily functioning and subjective events related to drug use with ecological momentary assessment (EMA).
Methods: EMA data were collected from cocaine- and heroin-using outpatients (72 men; 42 women) in methadone maintenance in 2-5 randomly prompted (RP) entries per day and in participant-initiated entries for heroin or cocaine use or craving, for up to 25 weeks. Urine drug screens were conducted three times weekly. Data were analyzed via repeated-measures logistic regression, using sex as a predictor of responses.
Results: In RP reports, women and men reported significantly different patterns of drug-cue exposure, with women significantly more likely to report having seen cocaine or been tempted to use in the past hour. Women also had higher craving after past-hour exposure to drug cues. In reports of drug use, women, compared to men, were more likely to report that they had used more cocaine than they had meant to, tended to feel guilty more often after drug use, and to have used despite trying not to use.
Conclusions: These findings provide real-time behavioral evidence that women respond differently than men to exposure to drug cues and to drug use, consistent with laboratory and brain-imaging findings. This information may be useful for development of sex-specific treatment strategies. Published by Elsevier Ireland Ltd.
C1 [Kennedy, Ashley P.; Epstein, David H.; Phillips, Karran A.; Preston, Kenzie L.] NIDA, NIH, Treatment Sect,Clin Pharmacol & Therapeut Res Bra, Intramural Res Program,Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
RP Preston, KL (reprint author), NIDA, Intramural Res Program, Clin Pharmacol & Therapeut Branch, Room 01B602,251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM kpreston@intra.nida.nih.gov
RI Preston, Kenzie/J-5830-2013
OI Preston, Kenzie/0000-0003-0603-2479
FU Intramural Research Program of the NIH National Institute on Drug Abuse
FX This research was supported by the Intramural Research Program of the
NIH National Institute on Drug Abuse.
NR 48
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U1 3
U2 26
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0376-8716
J9 DRUG ALCOHOL DEPEN
JI Drug Alcohol Depend.
PD SEP 1
PY 2013
VL 132
IS 1-2
BP 29
EP 37
DI 10.1016/j.drugalcdep.2012.12.025
PG 9
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 216KE
UT WOS:000324281400004
PM 23357742
ER
PT J
AU Wu, LT
Swartz, MS
Burchett, B
Blazer, DG
AF Wu, Li-Tzy
Swartz, Marvin S.
Burchett, Bruce
Blazer, Dan G.
CA NIDA AAPI Workgrp
TI Tobacco use among Asian Americans, Native Hawaiians/Pacific Islanders,
and mixed-race individuals: 2002-2010
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE Asian Americans; Mixed race; Pacific Islanders; Cigarette smoking;
Tobacco use; National Survery on Drug Use and Health (NSDUH)
ID UNITED-STATES; SMOKELESS TOBACCO; CIGARETTE-SMOKING; HEALTH;
ADOLESCENTS; MORTALITY
AB Background: Non-Hispanic Asian Americans, Native Hawaiians/Pacific Islanders (NHs/PIs), and mixed-race individuals are the fastest growing segments of the US population. We examined prevalences and correlates of tobacco use among these understudied groups. Prevalences among whites were included as a comparison.
Methods: Data were drawn from the 2002-2010 National Surveys on Drug Use and Health. Respondents aged >= 12 years were assessed for current (past-month) use of cigarettes, cigars, smokeless tobacco (chewing tobacco, snuff), and pipe tobacco. Respondents' race/ethnicity, age, sex, household income, government assistance, urbanicity of residence, residential stability, self-rated health, alcohol use, and drug use were examined as correlates.
Results: Between 2002 and 2010, there was a decline in the prevalence of cigarette smoking among whites (26.9% in 2002; 24.3% in 2010) and Asian Americans (18.0% in 2002; 11.1% in 2010). Prevalence of pipe tobacco use among mixed-race individuals increased from 0.2% in 2002 to 1.6% in 2010; there was little change in the prevalence of cigar and smokeless tobacco use in these racial/ethnic groups. Adjusted analyses showed that, compared with Asian Americans, mixed-race individuals had greater odds of using four tobacco products, and NHs/PIs had greater odds of using cigarettes, cigars, and smokeless tobacco. Regardless of race/ethnicity, male sex was a correlate of use of cigars, smokeless tobacco, and pipe tobacco; alcohol and drug use increased the odds of cigarette and cigar smoking.
Conclusions: These new findings show prevalent tobacco use among NHs/PIs and mixed-race individuals, and highlight the importance of including these populations in future research and reporting. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
C1 [Wu, Li-Tzy; Swartz, Marvin S.; Burchett, Bruce; Blazer, Dan G.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA.
[NIDA AAPI Workgrp] Natl Inst Drug Abuse Asian Amer & Pacific Islande, Bethesda, MD 20892 USA.
RP Wu, LT (reprint author), Duke Univ, Sch Med, Med Ctr, Dept Psychiat & Behav Sci, Box 3903, Durham, NC 27710 USA.
EM litzy.wu@duke.edu
FU U.S. National Institute on Drug Abuse of the National Institutes of
Health [HHSN271200900499P, R33DA027503, R01DA019623]; Duke University
FX This work was made possible by research support from the U.S. National
Institute on Drug Abuse of the National Institutes of Health
(HHSN271200900499P, R33DA027503, and R01DA019623 to LT Wu) and by Duke
University. The sponsoring agency had no further role in the study
design and analysis, the writing of the report, or the decision to
submit the paper for publication. The opinions expressed in this paper
are solely those of the authors.
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PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0376-8716
J9 DRUG ALCOHOL DEPEN
JI Drug Alcohol Depend.
PD SEP 1
PY 2013
VL 132
IS 1-2
BP 87
EP 94
DI 10.1016/j.drugalcdep.2013.01.008
PG 8
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 216KE
UT WOS:000324281400012
PM 23394689
ER
PT J
AU Hill, KP
Bennett, HE
Griffin, ML
Connery, HS
Fitzmaurice, GM
Subramaniam, G
Woody, GE
Weiss, RD
AF Hill, Kevin P.
Bennett, Heather E.
Griffin, Margaret L.
Connery, Hilary S.
Fitzmaurice, Garrett M.
Subramaniam, Geetha
Woody, George E.
Weiss, Roger D.
TI Association of cannabis use with opioid outcomes among opioid-dependent
youth
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE Cannabis use; Opioid dependence; Buprenorphine; Adolescent substance
abuse
ID METHADONE-MAINTENANCE; OPIATE-DEPENDENCE; MARIJUANA USE; TRIAL;
ADOLESCENTS
AB Objective: Cannabis use is common among opioid-dependent patients, but studies of its association with treatment outcome are mixed. In this secondary analysis, the association of cannabis use with opioid treatment outcome is assessed.
Methods: In the main study, participants (n=152) aged 15-21 years were randomized to receive psychosocial treatments and either a 12-week course of buprenorphine-naloxone with a dose taper to zero in weeks 9-12, or a 2-week detoxification with buprenorphine-naloxone. Drug use was assessed by self-report and urine drug screen at baseline and during study weeks 1-12. The association between cannabis and opioid use at weeks 4, 8, and 12 was examined using logistic regression models.
Results: Participants reported a median of 3.0 days (range = 0-30) cannabis use in the past month; half (50.3%; n=77) reported occasional use, one-third reported no use (33.1%; n = 50), and one-sixth reported daily cannabis use (16.6%; n = 25). Median lifetime cannabis use was 4.0 years (range = 0-11) and median age of initiation of use was 15.0 years (range 9-21). Neither past cannabis use (age of initiation and use in the month prior to baseline) nor concurrent use was associated with level of opioid use.
Conclusions: Overall, cannabis use had no association with opioid use over 12 weeks in this sample of opioid-dependent youth. While cannabis use remains potentially harmful, it was not a predictor of poor opioid treatment outcome. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
C1 [Hill, Kevin P.; Bennett, Heather E.; Griffin, Margaret L.; Connery, Hilary S.; Fitzmaurice, Garrett M.; Weiss, Roger D.] McLean Hosp, Div Alcohol & Drug Abuse, Belmont, MA 02478 USA.
[Hill, Kevin P.; Griffin, Margaret L.; Connery, Hilary S.; Fitzmaurice, Garrett M.; Weiss, Roger D.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Subramaniam, Geetha] NIDA, Ctr Clin Trials Network, Bethesda, MD 20892 USA.
[Woody, George E.] Univ Penn, Treatment Res Inst, Dept Psychiat, Philadelphia, PA 19106 USA.
RP Hill, KP (reprint author), McLean Hosp, 115 Mill St, Belmont, MA 02478 USA.
EM khill@mclean.harvard.edu
FU NIDA [K99/R00 DA029115, K24 DA022288]; NIDA CTN [U10 DA15831]; Adam
Corneel Young Investigator Fellowship from McLean Hospital
FX This study was supported by NIDA K99/R00 DA029115 (Kevin P. Hill, MD,
MHS, PI), NIDA K24 DA022288 (Roger D. Weiss, MD, PI), NIDA CTN U10
DA15831 and the Adam Corneel Young Investigator Fellowship from McLean
Hospital to Dr. Hill. The publications committee of the CTN gave final
approval of the analysis and interpretation of the data and approved the
manuscript.
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PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0376-8716
J9 DRUG ALCOHOL DEPEN
JI Drug Alcohol Depend.
PD SEP 1
PY 2013
VL 132
IS 1-2
BP 342
EP 345
DI 10.1016/j.drugalcdep.2013.02.030
PG 4
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 216KE
UT WOS:000324281400049
PM 23528523
ER
PT J
AU Compton, WM
Dawson, DA
Goldstein, RB
Grant, BF
AF Compton, Wilson M.
Dawson, Deborah A.
Goldstein, Rise B.
Grant, Bridget F.
TI Crosswalk between DSM-IV dependence and DSM-5 substance use disorders
for opioids, cannabis, cocaine and alcohol
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE DSM-IV; DSM-5; Substance use disorder; Concordance; Kappa; Diagnosis
ID NATIONAL EPIDEMIOLOGIC SURVEY; CONTROLLED-TRIAL; UNITED-STATES;
COMORBIDITY; PREVALENCE; DISABILITY; DIAGNOSIS; THERAPY; ADULTS; ABUSE
AB Background: Ascertaining agreement between DSM-IV and DSM-5 is important to determine the applicability of treatments for DSM-IV conditions to persons diagnosed according to the proposed DSM-5.
Methods: Data from a nationally representative sample of US adults were used to compare concordance of past-year DSM-IV opioid, cannabis, cocaine and alcohol dependence with past-year DSM-5 disorders at thresholds of 3+, 4+, 5+ and 6+ positive DSM-5 criteria among past-year users of opioids (n = 264), cannabis (n = 1622), cocaine (n = 271) and alcohol (n = 23,013). Substance-specific 2 x 2 tables yielded overall concordance (kappa), sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV).
Results: For DSM-IV alcohol, cocaine and opioid dependence, optimal concordance occurred when 4+ DSM-5 criteria were endorsed, corresponding to the threshold for moderate DSM-5 alcohol, cocaine and opioid use disorders. Maximal concordance of DSM-IV cannabis dependence and DSM-5 cannabis use disorder occurred when 6+ criteria were endorsed, corresponding to the threshold for severe DSM-5 cannabis use disorder. At these optimal thresholds, sensitivity, specificity, PPV and NPV generally exceeded 85% (>75% for cannabis).
Conclusions: Overall, excellent correspondence of DSM-IV dependence with DSM-5 substance use disorders was documented in this general population sample of alcohol, cannabis, cocaine and opioid users. Applicability of treatments tested for DSM-IV dependence is supported by these results for those with a DSM-5 alcohol, cocaine or opioid use disorder of at least moderate severity or severe cannabis use disorder. Further research is needed to provide evidence for applicability of treatments for persons with milder substance use disorders. Published by Elsevier Ireland Ltd.
C1 [Compton, Wilson M.] NIDA, Div Epidemiol Serv & Prevent Res, NIH, Bethesda, MD 20892 USA.
[Dawson, Deborah A.; Goldstein, Rise B.; Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, NIH, Bethesda, MD USA.
[Dawson, Deborah A.] Kelly Govt Serv, Bethesda, MD USA.
RP Compton, WM (reprint author), 6001 Execut Blvd,MSC 9589, Bethesda, MD 20892 USA.
EM wcompton@nida.nih.gov
OI Goldstein, Rise/0000-0002-9603-9473
FU National Institute on Alcohol Abuse and Alcoholism, National Institutes
of Health, US Department of Health and Human Services; National
Institutes of Health, National Institute on Alcohol Abuse and Alcoholism
FX The study on which this paper is based, the National Longitudinal
Alcohol Epidemiologic Survey (NLAES), is sponsored by the National
Institute on Alcohol Abuse and Alcoholism, National Institutes of
Health, US Department of Health and Human Services. This research was
supported in part by the Intramural Program of the National Institutes
of Health, National Institute on Alcohol Abuse and Alcoholism. All
authors are Federal government employees, and none of the authors has
any financial conflict of interest to report.
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PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0376-8716
J9 DRUG ALCOHOL DEPEN
JI Drug Alcohol Depend.
PD SEP 1
PY 2013
VL 132
IS 1-2
BP 387
EP 390
DI 10.1016/j.drugalcdep.2013.02.036
PG 4
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 216KE
UT WOS:000324281400057
PM 23642316
ER
PT J
AU Krijthe, BP
Kunst, A
Benjamin, EJ
Lip, GYH
Franco, OH
Hofman, A
Witteman, JCM
Stricker, BH
Heeringa, J
AF Krijthe, Bouwe P.
Kunst, Anton
Benjamin, Emelia J.
Lip, Gregory Y. H.
Franco, Oscar H.
Hofman, Albert
Witteman, Jacqueline C. M.
Stricker, Bruno H.
Heeringa, Jan
TI Projections on the number of individuals with atrial fibrillation in the
European Union, from 2000 to 2060
SO EUROPEAN HEART JOURNAL
LA English
DT Article
DE Atrial fibrillation; Epidemiology
ID HEART-FAILURE; GENERAL-POPULATION; STROKE PREVENTION; UNITED-STATES;
RISK-FACTOR; PREVALENCE; ROTTERDAM; TRENDS; MORTALITY; FLUTTER
AB Aims Since atrial fibrillation (AF) is associated with increased risks of cardiovascular and cerebrovascular complications, estimations on the number of individuals with AF are relevant to healthcare planning. We aimed to project the number of individuals with AF in the Netherlands and in the European Union from 2000 to 2060.
Methods and results Age-and sex-specific AF prevalence estimates were obtained from the prospective community-based Rotterdam Study. Population projections for the Netherlands and the European Union were obtained from the European Union's statistics office. In the age stratum of 55-59 years, the prevalence of AF was 1.3% in men (95% CI: 0.4-3.6%) and 1.7% in women (95% CI: 0.7-4.0%). The prevalence of AF increased to 24.2% in men (95% CI: 18.5-30.7%), and 16.1% in women (95% CI: 13.1-19.4%), for those >85 years of age. This age-and sex-specific prevalence remained stable during the years of follow-up. Furthermore, we estimate that in the European Union, 8.8 million adults over 55 years had AF in 2010 (95% CI: 6.5-12.3 million). We project that this number will double by 2060 to 17.9 million (95% CI: 13.6-23.7 million) if the age-and sex-specific prevalence remains stable.
Conclusion We estimate that from 2010 to 2060, the number of adults 55 years and over with AF in the European Union will more than double. As AF is associated with significant morbidities and mortality, this increasing number of individuals with AF may have major public health implications.
C1 [Krijthe, Bouwe P.; Franco, Oscar H.; Hofman, Albert; Witteman, Jacqueline C. M.; Stricker, Bruno H.; Heeringa, Jan] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands.
[Kunst, Anton] Univ Amsterdam, Amsterdam Med Ctr, Dept Publ Hlth, Amsterdam, Netherlands.
[Benjamin, Emelia J.] NHLBI, Framingham, MA USA.
[Benjamin, Emelia J.] Boston Univ Framingham Heart Study, Framingham, MA USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Evans Dept Med,Cardiol & Prevent Med Sect, Boston, MA 02118 USA.
[Lip, Gregory Y. H.] Univ Birmingham, City Hosp, Ctr Cardiovasc Sci, Birmingham, W Midlands, England.
[Stricker, Bruno H.] Inspectorate Hlth Care, The Hague, Netherlands.
RP Stricker, BH (reprint author), Erasmus MC, Dept Epidemiol, POB 2040, NL-3000 CA Rotterdam, Netherlands.
EM b.stricker@erasmusmc.nl
FU Erasmus Medical Center; Erasmus University Rotterdam; Netherlands
Organization for Scientific Research (NWO); Netherlands Organization for
Health Research and Development (ZonMw); Research Institute for Diseases
in the Elderly (RIDE); Netherlands Heart Foundation; Ministry of
Education, Culture and Science; Ministry of Health Welfare and Sports;
European Commission (DG XII); Municipality of Rotterdam;
[1R01HL092577]; [1R01 HL102214]; [1RC1HL101056]
FX The Rotterdam Study is supported by the Erasmus Medical Center and
Erasmus University Rotterdam; The Netherlands Organization for
Scientific Research (NWO); The Netherlands Organization for Health
Research and Development (ZonMw); the Research Institute for Diseases in
the Elderly (RIDE); The Netherlands Heart Foundation; the Ministry of
Education, Culture and Science; the Ministry of Health Welfare and
Sports; the European Commission (DG XII); and the Municipality of
Rotterdam. E.J.B. was funded by 1R01HL092577, 1R01 HL102214, and
1RC1HL101056.
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U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
J9 EUR HEART J
JI Eur. Heart J.
PD SEP
PY 2013
VL 34
IS 35
BP 2746
EP 2751
DI 10.1093/eurheartj/eht280
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 228FW
UT WOS:000325172300010
PM 23900699
ER
PT J
AU Wang, XF
Wang, SB
Ohkoshi, E
Wang, LT
Hamel, E
Qian, K
Morris-Natschke, SL
Lee, KH
Xie, L
AF Wang, Xiao-Feng
Wang, Sheng-Biao
Ohkoshi, Emika
Wang, Li-Ting
Hamel, Ernest
Qian, Keduo
Morris-Natschke, Susan L.
Lee, Kuo-Hsiung
Xie, Lan
TI N-Aryl-6-methoxy-1,2,3,4-tetrahydroquinolines: A novel class of
antitumor agents targeting the colchicine site on tubulin
SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
DE N-Aryl-6-methoxy-1,2,3,4-tetrahydroquinolines; Cytotoxicity; Tubulin
polymerization inhibitors; Colchicine binding site
ID VASCULAR DISRUPTING AGENTS; TUMOR-CELL LINES; CATALYZED AMINATION;
ANTICANCER DRUGS; DIVERSE PANEL; BINDING; POLYMERIZATION; DERIVATIVES;
INSIGHT; DESIGN
AB Structural optimizations of the prior lead 1a led to the discovery of a series of N-aryl-6-methoxy-1,2,3,4-tetrahydroquinoline derivatives as a novel class of tubulin polymerization inhibitors targeted at the colchicine binding site. The most active compound 6d showed extremely high cytotoxicity against a human tumor cell line panel (A549, KB, KBvin, and DU145) with GI(50) values ranging from 1.5 to 1.7 nM, significantly more potent than paclitaxel, especially against the drug-resistant KBvin cell line, in the same assays. Analogs 5f, 6b, 6c, and 6e were also quite potent, with a GI(50) range of 0.011-0.19 mu M. In further studies, active compounds 6b e and 5f significantly inhibited tubulin assembly, with IC50 values of 0.92 -1.0 mu M and strongly inhibited colchicine binding to tubulin, with inhibition rates of 75-99% (at 5 mu M), comparable with or more potent than combretastatin A-4 (IC50 0.96 mu M). Current studies included design, synthesis, and biological evaluations of 24 new compounds (series 3-6). Related SAR analysis, molecular modeling, and evaluation of essential drug-like properties, i.e. water solubility, log P, and in vitro metabolic stability, were also performed. (C) 2013 Elsevier Masson SAS. All rights reserved.
C1 [Wang, Xiao-Feng; Wang, Sheng-Biao; Xie, Lan] Beijing Inst Pharmacol & Toxicol, Beijing 100850, Peoples R China.
[Ohkoshi, Emika; Wang, Li-Ting; Qian, Keduo; Morris-Natschke, Susan L.; Lee, Kuo-Hsiung] Univ N Carolina, UNC Eshelman Sch Pharm, Nat Prod Res Labs, Chapel Hill, NC 27599 USA.
[Wang, Xiao-Feng] Urumqi Gen Hosp, Dept Pharm, Lanzhou Mil Region 830000, Urumqi, Peoples R China.
[Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program,NIH, Div Canc Treatment & Diagnosis,Frederick Natl Lab, Ft Detrick, MD 21702 USA.
[Lee, Kuo-Hsiung; Xie, Lan] China Med Univ & Hosp, Chinese Med Res & Dev, Taichung, Taiwan.
RP Xie, L (reprint author), Beijing Inst Pharmacol & Toxicol, 27 Tai Ping Rd, Beijing 100850, Peoples R China.
EM lanxieshi@yahoo.com
FU Natural Science Foundation of China (NSFC) [81120108022, 30930106]; NIH
from the National Cancer Institute [CA17625-32]; Taiwan Department of
Health, China Medical University Hospital Cancer Research Center of
Excellence [DOH100-TD-C-111-005]
FX This investigation was supported by Grants 81120108022 and 30930106 from
the Natural Science Foundation of China (NSFC) awarded to Dr. Lan Xie
and NIH Grant CA17625-32 from the National Cancer Institute awarded to
Dr. K. H. Lee. This study was also supported in part by the Taiwan
Department of Health, China Medical University Hospital Cancer Research
Center of Excellence (DOH100-TD-C-111-005).
NR 26
TC 16
Z9 17
U1 2
U2 34
PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
PI PARIS
PA 23 RUE LINOIS, 75724 PARIS, FRANCE
SN 0223-5234
EI 1768-3254
J9 EUR J MED CHEM
JI Eur. J. Med. Chem.
PD SEP
PY 2013
VL 67
BP 196
EP 207
DI 10.1016/j.ejmech.2013.06.041
PG 12
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 227NY
UT WOS:000325121800022
PM 23867604
ER
PT J
AU Lim, HJ
Dersch, CM
Rothman, RB
Deschamps, JR
Jacobson, AE
Rice, KC
AF Lim, Hwan Jung
Dersch, Christina M.
Rothman, Richard B.
Deschamps, Jeffrey R.
Jacobson, Arthur E.
Rice, Kenner C.
TI Probes for narcotic receptor mediated phenomena. 48. C7-and
C8-substituted 5-phenylmorphan opioids from diastereoselective
alkylation
SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
DE C7-and C8-substituted 5-phenylmorphans; Opioid receptor affinity;
"One-pot" diastereoselective synthesis
ID OXIDE-BRIDGED PHENYLMORPHANS; N-PHENETHYL ANALOGS; MU; AFFINITY;
ANTAGONIST; SERIES
AB The exploration of the effect of substituents at C7 and C8 of the 5-phenylmorphans on their affinity for opioid receptors was enabled by our recently introduced "one pot" diastereoselective synthesis that provided C7-oxo, hydroxy and alkyl substituents, C8-alkyl substituted 5-phenylmorphans, and compounds that had a new cyclohexane ring that includes the C7 and C8 carbon atoms of the 5-phenylmorphan. The affinity of the 5-phenylmorphans for opioid receptors is increased by a C8-methyl substituent, compared with its C7 analog. The affinity of the newly synthesized compounds is generally for the mu-opioid receptor, rather than the delta- or kappa-receptors. Addition of a new cyclohexane ring to the C7 and C8 positions on the cyclohexane ring of the 5-phenylmorphans enhances mu-receptor affinity, bringing the K-i to the subnanomolar level. Unexpectedly, the N-methyl substituted compounds generally had higher affinity than comparable N-phenethyl-substituted relatives. The configurations of two compounds were determined by single-crystal X-ray crystallographic analyses. Published by Elsevier Masson SAS.
C1 [Lim, Hwan Jung; Jacobson, Arthur E.; Rice, Kenner C.] Natl Inst Drug Abuse, NIH, Dept Hlth & Human Serv, Drug Design & Synth Sect,Chem Biol Res Branch, Bethesda, MD 20892 USA.
[Lim, Hwan Jung; Jacobson, Arthur E.; Rice, Kenner C.] Natl Inst Alcohol Abuse & Alcoholism, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Dersch, Christina M.; Rothman, Richard B.] Natl Inst Drug Abuse, Addict Res Ctr, NIH, Dept Hlth & Human Serv,Clin Psychopharmacol Sect, Baltimore, MD 21224 USA.
[Deschamps, Jeffrey R.] USN, Res Lab, Struct Matter Lab, Naval Res Lab, Washington, DC 20375 USA.
RP Rice, KC (reprint author), Natl Inst Drug Abuse, NIH, Dept Hlth & Human Serv, Drug Design & Synth Sect,Chem Biol Res Branch, 5625 Fishers Lane,Room 4N03, Bethesda, MD 20892 USA.
EM kr21f@nih.gov
OI Deschamps, Jeffrey/0000-0001-5845-0010
FU NIH Intramural Research Programs of the National Institute on Drug Abuse
(NIDA); National Institute of Alcohol Abuse and Alcoholism; NIH
Intramural Research Program of the National Institute on Drug Abuse
(NIDA); NIDA [Y1-DA1101]; Naval Research Laboratory (NRL)
FX The work of the Drug Design and Synthesis Section, CBRB, NIDA, & NIAAA,
was supported by the NIH Intramural Research Programs of the National
Institute on Drug Abuse (NIDA) and the National Institute of Alcohol
Abuse and Alcoholism. The Clinical Psychopharmacology Section, CBRB,
NIDA, was supported by the NIH Intramural Research Program of the
National Institute on Drug Abuse (NIDA). We also thank Dr. Klaus
Gawrisch and Dr. Walter Teague (Laboratory of Membrane Biochemistry and
Biophysics, NIAAA, for NMR spectral data). The authors also express
their thanks to Noel Whittaker, Mass Spectrometry Facility, NIDDK, for
mass spectral data. The X-ray crystallographic work was supported by
NIDA through an Interagency Agreement #Y1-DA1101 with the Naval Research
Laboratory (NRL).
NR 16
TC 1
Z9 1
U1 0
U2 5
PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
PI PARIS
PA 23 RUE LINOIS, 75724 PARIS, FRANCE
SN 0223-5234
EI 1768-3254
J9 EUR J MED CHEM
JI Eur. J. Med. Chem.
PD SEP
PY 2013
VL 67
BP 335
EP 343
DI 10.1016/j.ejmech.2013.06.030
PG 9
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 227NY
UT WOS:000325121800035
PM 23880358
ER
PT J
AU Fejzo, MS
Magtira, A
Schoenberg, FP
MacGibbon, K
Mullin, P
Romero, R
Tabsh, K
AF Fejzo, Marlena S.
Magtira, Aromalyn
Schoenberg, Frederic Paik
MacGibbon, Kimber
Mullin, Patrick
Romero, Roberto
Tabsh, Khalil
TI Antihistamines and other prognostic factors for adverse outcome in
hyperemesis gravidarum
SO EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY
LA English
DT Article
DE Hyperemesis gravidarum; Antihistamines; Fetal outcome; Nausea; Pregnancy
ID PARENTERAL-NUTRITION; PREGNANCY; NAUSEA; COMPLICATIONS; COHORT; WOMEN
AB Objective: The purpose of this study is to determine the frequency of adverse perinatal outcome in women with hyperemesis gravidarum and identify prognostic factors.
Study design: This is a case-control study in which outcomes of first pregnancies were compared between 254 women with hyperemesis gravidarum treated with intravenous fluids and 308 controls. Prognostic factors were identified by comparing the clinical profile of patients with hyperemesis gravidarum with a normal and an adverse pregnancy outcome. Binary responses were analyzed using either a Chi-square or Fisher exact test and continuous responses were analyzed using a t-test.
Results: Women with hyperemesis gravidarum have over a 4-fold increased risk of poor outcome including preterm birth and lower birth weight (p < 0.0001). Among maternal characteristics, only gestational hypertension had an influence on outcome (p < 0.0001). Treatment as an outpatient and/or by alternative medicine (acupuncture/acupressure/Bowen massage) was associated with a positive outcome (p < 0.0089). Poor outcomes were associated with early start of symptoms (p < 0.019), and treatment with methylprednisolone (p < 0.0217), promethazine (p < 0.0386), and other antihistamines [diphenhydramine (Benadryl), dimenhydrinate (Gravol), doxylamine (Unisom), hydroxyzine (Vistaril/Atarax), doxylamine and pyridoxine (Diclectin/Bendectin)] (p < 0.0151) independent of effectiveness. Among these medications, only the other antihistamines were prescribed independent of severity: they were effective in less than 20% of cases and were taken by almost 50% of patients with an adverse outcome.
Conclusion: Poor outcomes are significantly greater in women with HG and are associated with gestational hypertension, early symptoms, and antihistamine use. Given these results, there is an urgent need to address the safety and effectiveness of medications containing antihistamines in women with severe nausea of pregnancy. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
C1 [Fejzo, Marlena S.; Tabsh, Khalil] Univ Calif Los Angeles, Dept Obstet & Gynecol, Los Angeles, CA 90024 USA.
[Magtira, Aromalyn; Schoenberg, Frederic Paik] Univ Calif Los Angeles, Dept Stat, Los Angeles, CA USA.
[MacGibbon, Kimber] Hyperemesis Educ & Res Fdn, Leesburg, VA USA.
[Mullin, Patrick] Univ So Calif, Keck Sch Med, Dept Maternal Fetal Med, Los Angeles, CA 90033 USA.
[Romero, Roberto] NICHD, NIH, DHHS, Perinatol Res Branch,Dept Hlth & Human Serv, Bethesda, MD USA.
[Romero, Roberto] NICHD, NIH, DHHS, Perinatol Res Branch,Dept Hlth & Human Serv, Detroit, MI USA.
RP Fejzo, MS (reprint author), 675 Charles E Young Dr, Los Angeles, CA 90095 USA.
EM mfejzo@mednet.ucla.edu
OI MacGibbon, Kimber/0000-0002-6534-3114
FU Intramural NIH HHS [ZIA HD002400-22]
NR 21
TC 10
Z9 10
U1 1
U2 15
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0301-2115
J9 EUR J OBSTET GYN R B
JI Eur. J. Obstet. Gynecol. Reprod. Biol.
PD SEP
PY 2013
VL 170
IS 1
BP 71
EP 76
DI 10.1016/j.ejogrb.2013.04.017
PG 6
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 227OA
UT WOS:000325122000014
PM 23751910
ER
PT J
AU Handjaras, G
Ricciardi, E
Szczepanik, J
Pietrini, P
Furey, ML
AF Handjaras, Giacomo
Ricciardi, Emiliano
Szczepanik, Joanna
Pietrini, Pietro
Furey, Maura L.
TI Cholinergic enhancement differentially modulates neural response to
encoding during face identity and face location working memory tasks
SO EXPERIMENTAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Acetylcholinesterase inhibitors; cholinergic system; face perception;
working memory; fMRI; visual cortex
ID CEREBRAL-BLOOD-FLOW; CAT VISUAL-CORTEX; FUNCTIONAL-ORGANIZATION;
ATTENTIONAL FUNCTIONS; SPATIAL INTEGRATION; SELECTIVE ATTENTION;
EXTRASTRIATE CORTEX; ACETYLCHOLINE; COGNITION; SYSTEMS
AB Potentiation of cholinergic transmission influences stimulus processing by enhancing signal detection through suppression and/or filtering out of irrelevant information (bottom-up modulation) and with top-down task-oriented executive mechanisms based on the recruitment of prefrontal and parietal attentional systems. The cholinergic system also plays a critical role in working memory (WM) processes and preferentially modulates WM encoding, likely through stimulus-processing mechanisms. Previous research reported increased brain responses in visual extrastriate cortical regions during cholinergic enhancement in the encoding phase of WM, independently addressing object and spatial encoding. The current study used functional magnetic resonance imaging to determine the effects of cholinergic enhancement on encoding of key visual processing features. Subjects participated in two scanning sessions, one during an intravenous (i.v.) infusion of saline and the other during an infusion of the acetylcholinesterase inhibitor physostigmine. In each scan session, subjects alternated between a face identity recognition and a spatial location WM. Enhanced cholinergic function increased neural activity in the ventral stream during encoding of face identity and in the dorsal stream during encoding of face location. Conversely, a reduction in brain response was found for scrambled sensorimotor control images. The cholinergic effects on neural activity in the ventral stream during encoding of face identity were stronger than those observed in the dorsal stream during encoding of face location, likely as a consequence of the role of acetylcholine in establishing the inherently relevant nature of face identity. Despite the limited sample-size, the results suggest the stimulus-dependent role of cholinergic system in signal detection, as they show that cholinergic potentiation enhances neural activity in regions associated with early perceptual processing in a selective manner depending on the attended stimulus feature.
C1 [Handjaras, Giacomo; Ricciardi, Emiliano; Pietrini, Pietro] Univ Pisa, Lab Clin Biochem & Mol Biol, I-56126 Pisa, Italy.
[Handjaras, Giacomo; Pietrini, Pietro] Pisa Univ Hosp, Clin Psychol Branch, I-56126 Pisa, Italy.
[Szczepanik, Joanna; Furey, Maura L.] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA.
RP Ricciardi, E (reprint author), Univ Pisa, Lab Clin Biochem & Mol Biol, I-56126 Pisa, Italy.
EM emiliano.ricciardi@bioclinica.unipi.it
RI Ricciardi, Emiliano/E-6929-2011;
OI Ricciardi, Emiliano/0000-0002-7178-9534; Handjaras,
Giacomo/0000-0001-5677-8434
FU Intramural Research Program at the National Institute of Mental Health
[00-M-0056]
FX The authors thank James V. Haxby for input and support during early
stages of this project, and Sabrina Danti and Anna Gaglianese for
comments on an earlier version of the manuscript. The study was founded
by the Intramural Research Program at the National Institute of Mental
Health and approved by the Institutional Review Board (National
Institutes of Health Protocol 00-M-0056).
NR 47
TC 2
Z9 2
U1 0
U2 3
PU ROYAL SOC MEDICINE PRESS LTD
PI LONDON
PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND
SN 1535-3702
J9 EXP BIOL MED
JI Exp. Biol. Med.
PD SEP
PY 2013
VL 238
IS 9
BP 999
EP 1008
DI 10.1177/1535370213497326
PG 10
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 220LA
UT WOS:000324584000003
PM 23975732
ER
PT J
AU Nilsen, WJ
Pavel, M
AF Nilsen, Wendy J.
Pavel, Misha
TI Moving Behavioral Theories into the 21st Century
SO IEEE PULSE
LA English
DT Article
ID HEALTH; PEOPLE
C1 [Nilsen, Wendy J.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA.
[Pavel, Misha] Natl Sci Fdn, Arlington, VA 22230 USA.
RP Nilsen, WJ (reprint author), NIH, Off Behav & Social Sci Res, Bldg 10, Bethesda, MD 20892 USA.
EM nilsenwj@od.nih.gov
NR 9
TC 6
Z9 6
U1 0
U2 2
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 2154-2287
J9 IEEE PULSE
JI IEEE Pulse
PD SEP-OCT
PY 2013
VL 4
IS 5
BP 25
EP 28
DI 10.1109/MPUL.2013.2271682
PG 4
WC Engineering, Biomedical
SC Engineering
GA 224KH
UT WOS:000324883400008
PM 24056790
ER
PT J
AU Liew, SL
Agashe, H
Bhagat, N
Paek, A
Bulea, TC
AF Liew, Sook-Lei
Agashe, Harshavardhan
Bhagat, Nikunj
Paek, Andrew
Bulea, Thomas C.
TI A Clinical Roadmap for Brain-Neural Machine Interfaces
SO IEEE PULSE
LA English
DT Article
C1 [Liew, Sook-Lei] NINDS, NIH, Bethesda, MD 20892 USA.
[Agashe, Harshavardhan; Bhagat, Nikunj; Paek, Andrew] Univ Houston, Dept Elect & Comp Engn, Houston, TX 77004 USA.
[Bulea, Thomas C.] NIH, Dept Rehabil Med, Bethesda, MD 20892 USA.
RP Liew, SL (reprint author), NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM liews@mail.nih.gov
FU National Institutes of Health (NIH) [NS082045]; NSF [IIS-1313620]; TIRR
Memorial Hermann; University of Houston; Rice University; University
Hospital of Tubingen, Germany; Instituto Tecnologico y de Estudios
Superiores de Monterrey, Mexico
FX We thank Dr. Jose Contreras-Vidal and Dr. Surjo Soekadar for their kind
invitation to allow us to serve as scribes for the conference. This
conference was funded by the National Institutes of Health (NIH) (Grant
No. NS082045), NSF (Grant No. IIS-1313620), TIRR Memorial Hermann, the
University of Houston, Rice University, and University Hospital of
Tubingen, Germany. We also acknowledge the funding provided by the
Instituto Tecnologico y de Estudios Superiores de Monterrey, Mexico, and
industry sponsors.
NR 3
TC 2
Z9 2
U1 0
U2 3
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 2154-2287
J9 IEEE PULSE
JI IEEE Pulse
PD SEP-OCT
PY 2013
VL 4
IS 5
BP 44
EP 48
DI 10.1109/MPUL.2013.2271686
PG 5
WC Engineering, Biomedical
SC Engineering
GA 224KH
UT WOS:000324883400011
PM 24056793
ER
PT J
AU Klee, MM
AF Klee, Maurice M.
TI The Ebb and Flow of Patent Law
SO IEEE PULSE
LA English
DT Editorial Material
C1 [Klee, Maurice M.] Michigan State Univ, Coll Engn, E Lansing, MI 48824 USA.
[Klee, Maurice M.] NIH, Bethesda, MD USA.
EM mk@maurieklee.com
NR 0
TC 0
Z9 0
U1 0
U2 5
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 2154-2287
J9 IEEE PULSE
JI IEEE Pulse
PD SEP-OCT
PY 2013
VL 4
IS 5
BP 52
EP +
DI 10.1109/MPUL.2013.2271418
PG 2
WC Engineering, Biomedical
SC Engineering
GA 224KH
UT WOS:000324883400013
PM 24180026
ER
PT J
AU Jawad, S
Liu, BY
Li, ZY
Katamay, R
Campos, M
Wei, L
Sen, HN
Ling, D
Estrada, FM
Amaral, J
Chan, CC
Fariss, R
Gordon, S
Nussenblatt, RB
AF Jawad, Shayma
Liu, Baoying
Li, Zhiyu
Katamay, Robert
Campos, Mercedes
Wei, Lai
Sen, H. Nida
Ling, Diamond
Estrada, Fernando Martinez
Amaral, Juan
Chan, Chi-Chao
Fariss, Robert
Gordon, Siamon
Nussenblatt, Robert B.
TI The Role of Macrophage Class A Scavenger Receptors in a Laser-Induced
Murine Choroidal Neovascularization Model
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE AMD; CNV; macrophages; scavenger receptors
ID RETINAL-PIGMENT EPITHELIUM; MONOCYTE CHEMOTACTIC PROTEIN-3;
LOW-DENSITY-LIPOPROTEIN; FACTOR-H POLYMORPHISM; MACULAR DEGENERATION;
DEPENDENT PHAGOCYTOSIS; INFLAMMATORY RESPONSE; COMPLEMENT ACTIVATION;
HUMAN EOSINOPHILS; CHEMOKINE
AB PURPOSE. Laser-induced choroidal neovascularization (CNV) is a widely used model to mimic many features of CNV resulting from wet AMD. Macrophages have been implicated in the pathogenesis of AMD. Class A scavenger receptors, scavenger receptor-A (SR-A) and macrophage receptor with collagenous domain (MARCO), are expressed on macrophages and are associated with macrophage function. The goal of this study is to examine the role of macrophage scavenger receptors in immune cell recruitment and the formation of CNV.
METHODS. Laser photocoagulation was performed in wild-type and knockout mice with deletion of SR-A (SR-A(-/-)), MARCO (MARCO(-/-)), or both SR-A and MARCO double knockout (DKO). Immune cell recruitment at different time points and CNV lesions at 14 days after laser treatment were evaluated through immunostaining and confocal microscopy. Microarray analysis was performed in eyes 1 day after laser injury.
RESULTS. Wild-type eyes showed higher chemokine/receptor expression compared with knockout eyes after laser injury. Scavenger receptor deficiency markedly impaired the recruitment of neutrophils and macrophages to CNV lesions at 1- and 3-days post laser injury, respectively. Significantly reduced CNV volumes were found in the eyes from scavenger receptor knockout mice compared with wild-type mice.
CONCLUSIONS. The deficiency of scavenger receptors impairs the formation of CNV and immune cell recruitment. Our findings suggest a potential role for scavenger receptors in contributing to CNV formation and inflammation in AMD.
C1 [Jawad, Shayma; Liu, Baoying; Li, Zhiyu; Katamay, Robert; Wei, Lai; Sen, H. Nida; Ling, Diamond; Chan, Chi-Chao; Nussenblatt, Robert B.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Campos, Mercedes; Fariss, Robert] NEI, Biol Imaging Core, NIH, Bethesda, MD 20892 USA.
[Estrada, Fernando Martinez; Gordon, Siamon] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England.
[Amaral, Juan] NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Liu, BY (reprint author), Immunol Lab, Bldg 10,Room 10N112,10 Ctr Dr, Bethesda, MD 20892 USA.
EM liuba@nei.nih.gov; drbob@nei.nih.gov
RI Wei, Lai/D-1088-2014
FU National Institutes of Health, National Eye Institute
FX Supported by grants from the Intramural Research Program of National
Institutes of Health, National Eye Institute.
NR 92
TC 8
Z9 9
U1 0
U2 3
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD SEP
PY 2013
VL 54
IS 9
BP 5959
EP 5970
DI 10.1167/iovs.12-11380
PG 12
WC Ophthalmology
SC Ophthalmology
GA 228EV
UT WOS:000325169500005
PM 23927892
ER
PT J
AU Domalpally, A
Danis, RP
Chew, EY
Clemons, TE
Reed, S
SanGiovanni, JP
Ferris, FL
AF Domalpally, Amitha
Danis, Ronald P.
Chew, Emily Y.
Clemons, Traci E.
Reed, Susan
SanGiovanni, John Paul
Ferris, Frederick L., III
CA Age-Related Eye Dis Study 2 Res Gr
TI Evaluation of Optimized Digital Fundus Reflex Photographs for Lens
Opacities in the Age-Related Eye Disease Study 2: AREDS2 Report 7
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE cataract; lens opacity; AREDS2
ID CATARACT GRADING SYSTEM; REPORT NO. 4; TRIAL
AB PURPOSE. We described the system for grading lens opacities using stereoscopic digital fundus reflex photographs in the Age-Related Eye Disease Study 2 (AREDS2) and compared reproducibility with the AREDS lens grading system, which used retroillumination film images.
METHODS. Stereoscopic fundus reflex photographs were acquired in a standardized fashion at baseline and annually. Images were enhanced and evaluated in the red channel at a central reading center. Percentage involvement of cortical and posterior subcapsular (PSC) lens opacities within the central 5 mm diameter zone of a modified AREDS lens grid was estimated. Reproducibility was assessed for contemporaneous variability (ongoing, monthly regrade on 5% of submissions, n = 777 eyes) and temporal drift (regrading a subset of baseline photographs annually, n = 88).
RESULTS. In the contemporaneous exercise, the agreement for presence of cortical opacities was 93% (kappa = 0.86) and for PSC opacities it was 97% (kappa = 0.83). Intraclass correlation (ICC) for area of central zone involvement was 0.95 for cortical and 0.99 for PSC opacities. Historic data for contemporaneous regrading of film-based images in AREDS showed an ICC of 0.94 for cortical and 0.82 for PSC. The final annual temporal drift exercise had a reproducibility of 95% for cortical and PSC opacities.
CONCLUSIONS. Digital grading using fundus reflex images with image enhancing tools has reproducibility comparable to film-based retroillumination images, and may be useful for centralized objective lens opacity assessment in clinical trials using widely available fundus cameras. Red reflex images limit evaluation to cortical and PSC opacities, and do not permit assessment of nuclear opacities. (ClinicalTrials.gov number, NCT00345176.)
C1 [Domalpally, Amitha; Danis, Ronald P.; Reed, Susan] Fundus Photograph Reading Ctr, Dept Ophthalmol & Visual Sci, Madison, WI USA.
[Chew, Emily Y.; SanGiovanni, John Paul; Ferris, Frederick L., III] NEI, NIH, Bethesda, MD USA.
[Clemons, Traci E.] EMMES Corp, Rockville, MD USA.
RP Danis, RP (reprint author), Univ Wisconsin, Dept Ophthalmol & Visual Sci, 8010 Excelsior Dr, Madison, WI 53717 USA.
EM rpdanis@wisc.edu
RI Domalpally, Amitha/B-2367-2015
FU NIH [U10-EY013018, HHS-N-260-2005-00007-C]; Administrative Data Base
(ADB) [N01-EY-5-0007]
FX Supported by NIH Grant U10-EY013018 (RD) and intramural program funds
from NIH Contract No. HHS-N-260-2005-00007-C, and Administrative Data
Base (ADB) Contract No. N01-EY-5-0007.
NR 15
TC 2
Z9 3
U1 0
U2 2
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD SEP
PY 2013
VL 54
IS 9
BP 5989
EP 5994
DI 10.1167/iovs.13-12301
PG 6
WC Ophthalmology
SC Ophthalmology
GA 228EV
UT WOS:000325169500009
PM 23887802
ER
PT J
AU Sullivan, LS
Bowne, SJ
Reeves, MJ
Blain, D
Goetz, K
NDifor, V
Vitez, S
Wang, XJ
Tumminia, SJ
Daiger, SP
AF Sullivan, Lori S.
Bowne, Sara J.
Reeves, Melissa J.
Blain, Delphine
Goetz, Kerry
NDifor, Vida
Vitez, Sally
Wang, Xinjing
Tumminia, Santa J.
Daiger, Stephen P.
TI Prevalence of Mutations in eyeGENE Probands With a Diagnosis of
Autosomal Dominant Retinitis Pigmentosa
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE retinitis pigmentosa; eyeGENE; DNA sequencing; inherited retinal
diseases; mutation prevalences
ID DISEASE-CAUSING MUTATIONS; DEGENERATION SLOW GENE; RHODOPSIN GENE; POINT
MUTATION; FAMILIES; PROTEIN; IDENTIFICATION; ADRP; RPGR; OPHTHALMOLOGY
AB PURPOSE. To screen samples from patients with presumed autosomal dominant retinitis pigmentosa (adRP) for mutations in 12 disease genes as a contribution to the research and treatment goals of the National Ophthalmic Disease Genotyping and Phenotyping Network (eyeGENE).
METHODS. DNA samples were obtained from eyeGENE. A total of 170 probands with an intake diagnosis of adRP were tested through enrollment in eyeGENE. The 10 most common genes causing adRP (IMPDH1, KLHL7, NR2E3, PRPF3/RP18, PRPF31/RP11, PRPF8/RP13, PRPH2/RDS, RHO, RP1, and TOPORS) were chosen for PCR-based dideoxy sequencing, along with the two X-linked RP genes, RPGR and RP2. RHO, PRPH2, PRPF31, RPGR, and RP2 were completely sequenced, while only mutation hotspots in the other genes were analyzed.
RESULTS. Disease-causing mutations were identified in 52% of the probands. The frequencies of disease-causing mutations in the 12 genes were consistent with previous studies.
CONCLUSIONS. The Laboratory for Molecular Diagnosis of Inherited Eye Disease at the University of Texas in Houston has thus far received DNA samples from 170 families with a diagnosis of adRP from the eyeGENE Network. Disease-causing mutations in autosomal genes were identified in 48% (81/170) of these families while mutations in X-linked genes accounted for an additional 4% (7/170). Of the 55 distinct mutations detected, 19 (33%) have not been previously reported. All diagnostic results were returned by eyeGENE to participating patients via their referring clinician. These genotyped samples along with their corresponding phenotypic information are also available to researchers who may request access to them for further study of these ophthalmic disorders.
C1 [Sullivan, Lori S.; Bowne, Sara J.; Daiger, Stephen P.] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA.
[Reeves, Melissa J.; Blain, Delphine; Goetz, Kerry; NDifor, Vida; Vitez, Sally; Wang, Xinjing] NEI, NIH, Ophthalm Genet & Visual Funct Branch, Bethesda, MD 20892 USA.
[Tumminia, Santa J.] NEI, NIH, Off Director, Bethesda, MD 20892 USA.
RP Daiger, SP (reprint author), Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA.
EM stephen.p.daiger@uth.tmc.edu
FU National Institutes of Health/National Eye Institute (NIH/NEI)
[HHS-N-260-2007-00001-C]; National Ophthalmic Genotyping and Phenotyping
Network of the NEI, or eyeGENE; NIH/NEI [EY007142]; Foundation Fighting
Blindness; CLIA Certified Laboratory [45D0935007]
FX Supported by the National Institutes of Health/National Eye Institute
(NIH/NEI) under Contract No. HHS-N-260-2007-00001-C; by the National
Ophthalmic Genotyping and Phenotyping Network of the NEI, or eyeGENE (a
registered trademark of the National Institutes of Health) (Protocol
06-EI-0236); by NIH/NEI Grant EY007142; and by Center and Module grants
from the Foundation Fighting Blindness. Stephen P. Daiger is Director of
a CLIA Certified Laboratory (45D0935007) in the eyeGENE Network.
NR 47
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U1 0
U2 9
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD SEP
PY 2013
VL 54
IS 9
BP 6255
EP 6261
DI 10.1167/iovs.13-12605
PG 7
WC Ophthalmology
SC Ophthalmology
GA 228EV
UT WOS:000325169500041
PM 23950152
ER
PT J
AU Armstrong, J
Mitnitski, A
Launer, L
White, L
Rockwood, K
AF Armstrong, J.
Mitnitski, A.
Launer, L.
White, L.
Rockwood, K.
TI Frailty in Relation to Late-Life Cognition: Poisson Regression Models in
Data from the Honolulu-Asian Aging Study
SO IRISH JOURNAL OF MEDICAL SCIENCE
LA English
DT Meeting Abstract
C1 [Armstrong, J.; Mitnitski, A.; Rockwood, K.] Dalhousie Univ, Halifax, NS, Canada.
[Launer, L.] NIA, Bethesda, MD 20892 USA.
[White, L.] Univ Hawaii, Honolulu, HI 96822 USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU SPRINGER LONDON LTD
PI LONDON
PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND
SN 0021-1265
J9 IRISH J MED SCI
JI Irish J. Med. Sci.
PD SEP
PY 2013
VL 182
SU 6
BP S237
EP S237
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 217CU
UT WOS:000324335000086
ER
PT J
AU Arakelyan, A
Fitzgerald, W
Margolis, L
Grivel, JC
AF Arakelyan, Anush
Fitzgerald, Wendy
Margolis, Leonid
Grivel, Jean-Charles
TI Nanoparticle-based flow virometry for the analysis of individual virions
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; CELL-MEMBRANE-PROTEINS; CUCUMBER
MOSAIC-VIRUS; HOST HLA-DR; OPPORTUNISTIC INFECTION; HIV-1 INFECTION;
IN-VIVO; CYTOMETRY; PARTICLES; ANTIBODY
AB While flow cytometry has been used to analyze the antigenic composition of individual cells, the antigenic makeup of viral particles is still characterized predominantly in bulk. Here, we describe a technology, "flow virometry," that can be used for antigen detection on individual virions. The technology is based on binding magnetic nanoparticles to virions, staining the virions with monoclonal antibodies, separating the formed complexes with magnetic columns, and characterizing them with flow cytometers. We used this technology to study the distribution of two antigens (HLA-DR and LFA-1) that HIV-1 acquires from infected cells among individual HIV-1 virions. Flow virometry revealed that the antigenic makeup of virions from a single preparation is heterogeneous. This heterogeneity could not be detected with bulk analysis of viruses. Moreover, in two preparations of the same HIV-1 produced by different cells, the distribution of antigens among virions was different. In contrast, HIV-1 of two different HIV-1 genotypes replicating in the same cells became somewhat antigenically similar. This nanotechnology allows the study of virions in bodily fluids without virus propagation and in principle is not restricted to the analysis of HIV, but can be applied to the analysis of the individual surface antigenic makeup of any virus.
C1 [Arakelyan, Anush; Fitzgerald, Wendy; Margolis, Leonid; Grivel, Jean-Charles] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD USA.
RP Margolis, L (reprint author), NIH, 10 Ctr Dr,Bldg 10,Rm 9D58, Bethesda, MD 20892 USA.
EM margolis@helix.nih.gov; grivelj@mail.nih.gov
FU NCI, NIH [HHSN261200800001E]; intramural program of the Eunice
Kennedy-Shriver National Institute of Child Health and Human Development
FX The authors would like to thank John Mascola for providing VRC01, Tome
Hope for providing GFP-expressing HIV-1, Mimi Gosh for providing samples
of CVL, and Michael Lederman for providing plasma samples obtained from
HIV-1-infected patients. These experiments used reagents provided by the
AIDS and Cancer Virus Program, SAIC Frederick, Inc./National Cancer
Institute (NCI), Frederick, supported with Federal funds from the NCI,
NIH, under contract HHSN261200800001E. We are grateful to Elena Zaitseva
for her excellent guidance in staining virions with lipophilic dyes and
to Sonia Zicari for her generous help with dengue viruses. We are
thankful to Jeremy Swan and Yumiko Shepherd for the preparation of
Figure 1. This work was supported by the intramural program of the
Eunice Kennedy-Shriver National Institute of Child Health and Human
Development.
NR 47
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U1 3
U2 21
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD SEP
PY 2013
VL 123
IS 9
BP 3716
EP 3727
DI 10.1172/JCI67042
PG 12
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 220DQ
UT WOS:000324562600017
PM 23925291
ER
PT J
AU Yang, JY
Yoshihara, K
Tanaka, K
Hatae, M
Masuzaki, H
Itamochi, H
Takano, M
Ushijima, K
Tanyi, JL
Coukos, G
Lu, YL
Mills, GB
Verhaak, RGW
AF Yang, Ji-Yeon
Yoshihara, Kosuke
Tanaka, Kenichi
Hatae, Masayuki
Masuzaki, Hideaki
Itamochi, Hiroaki
Takano, Masashi
Ushijima, Kimio
Tanyi, Janos L.
Coukos, George
Lu, Yiling
Mills, Gordon B.
Verhaak, Roel G. W.
CA Canc Genome Atlas TOGA Res Network
TI Predicting time to ovarian carcinoma recurrence using protein markers
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID ANDROGEN RECEPTOR EXPRESSION; PROPORTIONAL HAZARDS MODEL;
GYNECOLOGIC-ONCOLOGY-GROUP; FALSE DISCOVERY RATE; FUNCTIONAL ANNOTATION;
PROTEOMIC ANALYSIS; PROGNOSTIC-FACTORS; CANCER STATISTICS; SEROUS
CARCINOMA; GENE-EXPRESSION
AB Patients with ovarian cancer are at high risk of tumor recurrence. Prediction of therapy outcome may provide therapeutic avenues to improve patient outcomes. Using reverse-phase protein arrays, we generated ovarian carcinoma protein expression profiles on 412 cases from TCGA and constructed a PRotein-driven index of OVARian cancer (PROVAR). PROVAR significantly discriminated an independent cohort of 226 high-grade serous ovarian carcinomas into groups of high risk and low risk of tumor recurrence as well as short-term and long-term survivors. Comparison with gene expression-based outcome classification models showed a significantly improved capacity of the protein-based PROVAR to predict tumor progression. Identification of protein markers linked to disease recurrence may yield insights into tumor biology. When combined with features known to be associated with outcome, such as BRCA mutation, PROVAR may provide clinically useful predictions of time to tumor recurrence.
C1 [Yang, Ji-Yeon; Yoshihara, Kosuke; Verhaak, Roel G. W.] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77230 USA.
[Yoshihara, Kosuke; Tanaka, Kenichi] Niigata Univ, Grad Sch Med & Dent Sci, Dept Obstet & Gynecol, Niigata, Japan.
[Tanaka, Kenichi] Niigata Med Ctr Hosp, Niigata, Japan.
[Hatae, Masayuki] Kagoshima City Hosp, Dept Obstet & Gynecol, Kagoshima, Japan.
[Masuzaki, Hideaki] Nagasaki Univ, Sch Med, Dept Obstet & Gynecol, Nagasaki 852, Japan.
[Itamochi, Hiroaki] Tottori Univ, Sch Med, Dept Obstet & Gynecol, Tottori 680, Japan.
[Canc Genome Atlas TOGA Res Network] NCI, NIH, Bethesda, MD 20892 USA.
[Takano, Masashi] Natl Def Med Coll, Dept Obstet & Gynecol, Tokorozawa, Saitama 359, Japan.
[Ushijima, Kimio] Kurume Univ, Sch Med, Dept Obstet & Gynecol, Kurume, Fukuoka 830, Japan.
[Tanyi, Janos L.; Coukos, George] Univ Penn, Div Gynecol Oncol, Philadelphia, PA 19104 USA.
[Lu, Yiling; Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77230 USA.
RP Verhaak, RGW (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, 1400 Pressler Dr,Unit 1410, Houston, TX 77230 USA.
EM rverhaak@mdanderson.org
OI Yoshihara, Kosuke/0000-0002-2254-3378
FU NCI [5 P50 CA083639-12, CA143883, P50 CA083639]; MD Anderson RPPA Core
Facility; NIH [CA016672]
FX The results published here are in whole or part based upon data
generated by the TCGA pilot project established by the National Cancer
Institute (NCI) and NHGRI. Information about TCGA and the investigators
and institutions who constitute TCGA research network can be found at
http://cancergenome.nih.gov/. This work is supported by NCI award no. 5
P50 CA083639-12 (to R.G.W. Verhaak), NCI grant no. CA143883 (MD Anderson
Genome Data Analysis Center) and P50 CA083639 (to G.B. Mills), and MD
Anderson RPPA Core Facility (supported by NIH grant CA016672).
NR 50
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U1 0
U2 8
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD SEP
PY 2013
VL 123
IS 9
BP 3740
EP 3750
DI 10.1172/JCI68509
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 220DQ
UT WOS:000324562600019
PM 23945238
ER
PT J
AU Liu, WL
Yan, M
Sugui, JA
Li, HZ
Xu, CF
Joo, J
Kwon-Chung, KJ
Coleman, WG
Rodgers, GP
AF Liu, Wenli
Yan, Ming
Sugui, Janyce A.
Li, Hongzhen
Xu, Chengfu
Joo, Jungsoo
Kwon-Chung, Kyung J.
Coleman, William G.
Rodgers, Griffin P.
TI Olfm4 deletion enhances defense against Staphylococcus aureus in chronic
granulomatous disease
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID ASPERGILLUS-FUMIGATUS; INNATE IMMUNITY; RHIZOPUS-ORYZAE; MICE;
NEUTROPHILS; ACTIVATION; INFECTION; PROTEASES; INVITRO; HYPHAE
AB Chronic granulomatous disease (CGD) patients have recurrent life-threatening bacterial and fungal infections. Olfactomedin 4 (OLFM4) is a neutrophil granule protein that negatively regulates host defense against bacterial infection. The goal of this study was to evaluate the impact of Olfm4 deletion on host defense against Staphylococcus aureus and Aspergillus fumigatus in a murine X-linked gp91pbox-deficiency CGD model. We found that intracellular killing and in vivo clearance of S. aureus, as well as resistance to S. aureus sepsis, were significantly increased in gp91phox and Olfm4 double-deficient mice compared with CGD mice. The activities of cathepsin C and its downstream proteases (neutrophil elastase and cathepsin G) and serum levels of IL-1 beta, IL-6, IL-12p40, CXCL2, G-CSF, and GM-CSF in Olfm4-deficient as well as gp91phox and Olfm4 double-deficient mice were significantly higher than those in WT and CGD mice after challenge with S. aureus. We did not observe enhanced defense against A. fumigatus in Olfm4-deficient mice using a lung infection model. These results show that Olfm4 deletion can successfully enhance immune defense against S. aureus, but not A. fumigatus, in CGD mice. These data suggest that OLFM4 may be an important target in CGD patients for the augmentation of host defense against bacterial infection.
C1 [Liu, Wenli; Li, Hongzhen; Rodgers, Griffin P.] NHLBI, Mol & Clin Hematol Branch, Bethesda, MD 20892 USA.
[Yan, Ming; Xu, Chengfu; Joo, Jungsoo; Coleman, William G.] NIDDK, Lab Biochem & Genet, Bethesda, MD 20892 USA.
[Sugui, Janyce A.; Kwon-Chung, Kyung J.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Rodgers, GP (reprint author), NHLBI, Mol & Clin Hematol Branch, NIH, Bldg 10,Room 9N119,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM wcoleman@helix.nih.gov; gr5n@nih.gov
NR 23
TC 17
Z9 17
U1 0
U2 2
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD SEP
PY 2013
VL 123
IS 9
BP 3751
EP 3755
DI 10.1172/JCI68453
PG 5
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 220DQ
UT WOS:000324562600020
PM 23908114
ER
PT J
AU Goyama, S
Schibler, J
Cunningham, L
Zhang, Y
Rao, Y
Nishimoto, N
Nakagawa, M
Olsson, A
Wunderlich, M
Link, KA
Mizukawa, B
Grimes, HL
Kurokawa, M
Liu, PP
Huang, G
Mulloy, JC
AF Goyama, Susumu
Schibler, Janet
Cunningham, Lea
Zhang, Yue
Rao, Yalan
Nishimoto, Nahoko
Nakagawa, Masahiro
Olsson, Andre
Wunderlich, Mark
Link, Kevin A.
Mizukawa, Benjamin
Grimes, H. Leighton
Kurokawa, Mineo
Liu, P. Paul
Huang, Gang
Mulloy, James C.
TI Transcription factor RUNX1 promotes survival of acute myeloid leukemia
cells
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID METHYLTRANSFERASE GENE EZH2; HEMATOPOIETIC STEM-CELLS; MYELODYSPLASTIC
SYNDROME; ADULT HEMATOPOIESIS; MLL-AF9 LEUKEMIA; SOMATIC MUTATIONS;
PROGENITOR CELLS; SELF-RENEWAL; DIFFERENTIATION; LEUKEMOGENESIS
AB RUNX1 is generally considered a tumor suppressor in myeloid neoplasms. Inactivating RUNX1 mutations have frequently been found in patients with myelodysplastic syndrome (MDS) and cytogenetically normal acute myeloid leukemia (AML). However, no somatic RUNX1 alteration was found in AMLs with leukemogenic fusion proteins, such as core-binding factor (CBF) leukemia and MLL fusion leukemia, raising the possibility that RUNX1 could actually promote the growth of these leukemia cells. Using normal human cord blood cells and those expressing leukemogenic fusion proteins, we discovered a dual role of RUNX1 in myeloid leukemogenesis. RUNX1 overexpression inhibited the growth of normal cord blood cells by inducing myeloid differentiation, whereas a certain level of RUNX1 activity was required for the growth of AML1-ETO and MLL-AF9 cells. Using a mouse genetic model, we also showed that the combined loss of Runx1/Cbfb inhibited leukemia development induced by MLL-AF9. RUNX2 could compensate for the loss of RUNX1. The survival effect of RUNX1 was mediated by BCL2 in MLL fusion leukemia. Our study unveiled an unexpected prosurvival role for RUNX1 in myeloid leukemogenesis. Inhibiting RUNX1 activity rather than enhancing it could be a promising therapeutic strategy for AMLs with leukemogenic fusion proteins.
C1 [Goyama, Susumu; Schibler, Janet; Zhang, Yue; Rao, Yalan; Wunderlich, Mark; Link, Kevin A.; Mizukawa, Benjamin; Grimes, H. Leighton; Huang, Gang; Mulloy, James C.] Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA.
[Cunningham, Lea; Liu, P. Paul] NIH, Natl Canc Inst, Ctr Canc Res, Oncogenesis & Dev Sect, Bethesda, MD 20892 USA.
[Nishimoto, Nahoko; Nakagawa, Masahiro; Kurokawa, Mineo] Univ Tokyo, Grad Sch Med, Dept Hematol & Oncol, Tokyo, Japan.
[Olsson, Andre; Grimes, H. Leighton] Cincinnati Childrens Hosp Med Ctr, Div Immunobiol, Cincinnati, OH 45229 USA.
RP Mulloy, JC (reprint author), Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA.
EM james.mulloy@cchmc.org
RI Liu, Paul/A-7976-2012;
OI Liu, Paul/0000-0002-6779-025X; Grimes, H. Leighton/0000-0001-8162-6758
FU Institutional Clinical and Translational Science Award; NIH/NCRR grant
[1UL1RR026314-01]; Translational Trials Development and Support
Laboratory award (USPHS) [MO1 RR 08084]; a Center of Excellence in
Molecular Hematology P30 award [DK090971]; Cancer Free Kids Foundation
for Cancer Research; Intramural Research Program of the National Human
Genome Research Institute, NIH; JSPS Postdoctoral Fellowship
FX We thank the Flow Cytometry Core, the Mouse Core, and the Microarray
Core at Cincinnati Children's Hospital Medical Center for their help.
This work was supported by an Institutional Clinical and Translational
Science Award; an NIH/NCRR grant (1UL1RR026314-01); a Translational
Trials Development and Support Laboratory award (USPHS, MO1 RR 08084); a
Center of Excellence in Molecular Hematology P30 award (DK090971); a
grant from the Cancer Free Kids Foundation for Cancer Research (to J.C.
Mulloy and S. Goyama); a grant from the Intramural Research Program of
the National Human Genome Research Institute, NIH (to P.P. Liu); and a
JSPS Postdoctoral Fellowship for Research Abroad (to S. Goyama). J.C.
Mulloy is a Leukemia and Lymphoma Society Scholar. The contents of the
manuscript are solely the responsibility of the authors and donor
necessarily represent the official views of the NIH.
NR 53
TC 38
Z9 39
U1 0
U2 7
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD SEP
PY 2013
VL 123
IS 9
BP 3876
EP 3888
DI 10.1172/JCI68557
PG 13
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 220DQ
UT WOS:000324562600032
PM 23979164
ER
PT J
AU Nayak, G
Lee, SI
Yousaf, R
Edelmann, SE
Trincot, C
Van Itallie, CM
Sinha, GP
Rafeeq, M
Jones, SM
Belyantseva, IA
Anderson, JM
Forge, A
Frolenkov, GI
Riazuddinl, S
AF Nayak, Gowri
Lee, Sue I.
Yousaf, Rizwan
Edelmann, Stephanie E.
Trincot, Claire
Van Itallie, Christina M.
Sinha, Ghanshyam P.
Rafeeq, Maria
Jones, Sherri M.
Belyantseva, Inna A.
Anderson, James M.
Forge, Andrew
Frolenkov, Gregory I.
Riazuddinl, Saima
TI Tricellulin deficiency affects tight junction architecture and cochlear
hair cells
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID STRIA VASCULARIS; INNER-EAR; INTERCELLULAR-JUNCTIONS; EPITHELIAL-CELLS;
BARRIER FUNCTION; EXPRESSION; HEARING; DEAFNESS; OCCLUDIN;
ELECTROMOTILITY
AB The two compositionally distinct extracellular cochlear fluids, endolymph and perilymph, are separated by tight junctions that outline the scala media and reticular lamina. Mutations in TRIC (also known as MARVELD2), which encodes a tricellular tight junction protein known as tricellulin, lead to nonsyndromic hearing loss (DFNB49). We generated a knockin mouse that carries a mutation orthologous to the TRIC coding mutation linked to DFNB49 hearing loss in humans. Tricellulin was absent from the tricellular junctions in the inner ear epithelia of the mutant animals, which developed rapidly progressing hearing loss accompanied by loss of mechanosensory cochlear hair cells, while the endocochlear potential and paracellular permeability of a biotin-based tracer in the stria vascularis were unaltered. Freeze-fracture electron microscopy revealed disruption of the strands of intramembrane particles connecting bicellular and tricellular junctions in the inner ear epithelia of tricellulin-deficient mice. These ultrastructural changes may selectively affect the paracellular permeability of ions or small molecules, resulting in a toxic microenvironment for cochlear hair cells. Consistent with this hypothesis, hair cell loss was rescued in tricellulin-deficient mice when generation of normal endolymph was inhibited by a concomitant deletion of the transcription factor, Pou3f4. Finally, comprehensive phenotypic screening showed a broader pathological phenotype in the mutant mice, which highlights the non-redundant roles played by tricellulin.
C1 [Nayak, Gowri; Yousaf, Rizwan; Trincot, Claire; Riazuddinl, Saima] Cincinnati Childrens Hosp Res Fdn, Div Pediat Otolaryngol Head & Neck Surg, Mol Genet Lab, Cincinnati, OH 45229 USA.
[Nayak, Gowri; Yousaf, Rizwan; Trincot, Claire; Riazuddinl, Saima] Univ Cincinnati, Coll Med, Dept Otolaryngol, Cincinnati, OH USA.
[Lee, Sue I.; Belyantseva, Inna A.] NIDCD, Sect Human Genet, Mol Genet Lab, NIH, Rockville, MD USA.
[Edelmann, Stephanie E.; Sinha, Ghanshyam P.; Frolenkov, Gregory I.] Univ Kentucky, Dept Physiol, Lexington, KY USA.
[Van Itallie, Christina M.; Anderson, James M.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Rafeeq, Maria] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan.
[Jones, Sherri M.] Univ Nebraska, Dept Special Educ & Commun Disorders, Omaha, NE 68182 USA.
[Forge, Andrew] UCL, Ctr Auditory Res, London, England.
RP Riazuddinl, S (reprint author), Cincinnati Childrens Hosp Res Fdn, Mol Genet Lab, 3333 Burnet Ave,MLC2018, Cincinnati, OH 45229 USA.
EM Saima.Riazuddin@cchmc.org
OI Frolenkov, Gregory/0000-0002-9810-5024
FU Deafness Research Foundation grant; Action on Hearing Loss grant;
National Institute on Deafness and Other Communication Disorders
(NIDCD/NIH) [R01 DC011748, DC011803, R01 DC006443, R01 DC009434,
DC000039-15]; International Center for Genetic Engineering and
Biotechnology, Trieste, Italy [CRP/PAK08-01]
FX We thank Thomas Friedman, Zubair Ahmed, Elodie Richard, and Arnaud Giese
for critiques of our ideas and manuscript, Elizabeth Wilson for
genotyping and maintaining our mouse colonies, and Manna Li and Kira
Rehn for technical assistance. We also thank Penelope Friedman for her
review of the Tric knockin mice biochemical and histology results. This
work was supported by a Deafness Research Foundation grant, Action on
Hearing Loss grant, and National Institute on Deafness and Other
Communication Disorders (NIDCD/NIH) research grants (R01 DC011748 and
DC011803 to S. Riazuddin; R01 DC006443 to S.M. Jones; R01 DC009434 to
G.I. Frolenkov; the intramural funds from NIDCD DC000039-15) as well as
the International Center for Genetic Engineering and Biotechnology,
Trieste, Italy (project CRP/PAK08-01).
NR 59
TC 29
Z9 29
U1 1
U2 14
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD SEP
PY 2013
VL 123
IS 9
BP 4036
EP 4049
DI 10.1172/JCI69031
PG 14
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 220DQ
UT WOS:000324562600044
PM 23979167
ER
PT J
AU Das, A
Tanigawa, S
Karner, CM
Xin, M
Lum, L
Chen, C
Olson, EN
Perantoni, AO
Carroll, TJ
AF Das, Amrita
Tanigawa, Shunsuke
Karner, Courtney M.
Xin, Mei
Lum, Lawrence
Chen, Chuo
Olson, Eric N.
Perantoni, Alan O.
Carroll, Thomas J.
TI Stromal-epithelial crosstalk regulates kidney progenitor cell
differentiation
SO NATURE CELL BIOLOGY
LA English
DT Article
ID TUMOR-SUPPRESSOR PATHWAY; HIPPO PATHWAY; CARDIOMYOCYTE PROLIFERATION;
RENAL DEVELOPMENT; HEART SIZE; GROWTH; CONSERVATION; FAT; MORPHOGENESIS;
DISRUPTION
AB Present models suggest that the fate of the kidney epithelial progenitors is solely regulated by signals from the adjacent ureteric bud. The bud provides signals that regulate the survival, renewal and differentiation of these cells. Recent data suggest that Wnt9b, a ureteric-bud-derived factor, is sufficient for both progenitor cell renewal and differentiation. How the same molecule induces two seemingly contradictory processes is unknown. Here, we show that signals from the stromal fibroblasts cooperate with Wnt9b to promote differentiation of the progenitors. The atypical cadherin Fat4 encodes at least part of this stromal signal. Our data support a model whereby proper kidney size and function is regulated by balancing opposing signals from the ureteric bud and stroma to promote renewal and differentiation of the nephron progenitors.
C1 [Das, Amrita; Karner, Courtney M.; Carroll, Thomas J.] Univ Texas SW Med Ctr Dallas, Dept Internal Med Nephrol, Dallas, TX 75390 USA.
[Das, Amrita; Karner, Courtney M.; Xin, Mei; Olson, Eric N.; Carroll, Thomas J.] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA.
[Tanigawa, Shunsuke; Perantoni, Alan O.] NCI, Canc & Dev Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Lum, Lawrence] Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA.
[Chen, Chuo] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
RP Carroll, TJ (reprint author), Univ Texas SW Med Ctr Dallas, Dept Internal Med Nephrol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM Thomas.carroll@utsouthwestern.edu
OI Chen, Chuo/0000-0002-3118-4901
FU Japanese Society for the Promotion of Science; NIH [R01DK080004,
R01DK095057]; National Cancer Institute's Center for Cancer Research;
George O'Brien Kidney Research Center at UTSW
FX We thank Y. Yang (NIH, USA) for providing the Vangl2 mutant mice, M.
Takeichi (RIKEN Center for Developmental Biology, Japan) for providing
the Fat4 full-length and ECD plasmids, J. Cabera for artwork and O.
Cleaver, Q. Li and D. Marciano for reading and commenting on the
manuscript. This work was supported by a post-doctoral fellowship from
the A.H.A. to A.D. and from the Japanese Society for the Promotion of
Science to S.T., the NIH (R01DK080004 and R01DK095057 to T.C.) and
National Cancer Institute's Center for Cancer Research (A.P.). This work
was supported by the George O'Brien Kidney Research Center at UTSW.
NR 33
TC 51
Z9 51
U1 0
U2 16
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1465-7392
EI 1476-4679
J9 NAT CELL BIOL
JI Nat. Cell Biol.
PD SEP
PY 2013
VL 15
IS 9
BP 1035
EP +
DI 10.1038/ncb2828
PG 22
WC Cell Biology
SC Cell Biology
GA 213IP
UT WOS:000324050000004
PM 23974041
ER
PT J
AU Ezan, J
Lasvaux, L
Gezer, A
Novakovic, A
May-Simera, H
Belotti, E
Lhoumeau, AC
Birnbaumer, L
Beer-Hammer, S
Borg, JP
Le Bivic, A
Nurnberg, B
Sans, N
Montcouquiol, M
AF Ezan, Jerome
Lasvaux, Lea
Gezer, Aysegul
Novakovic, Ana
May-Simera, Helen
Belotti, Edwige
Lhoumeau, Anne-Catherine
Birnbaumer, Lutz
Beer-Hammer, Sandra
Borg, Jean-Paul
Le Bivic, Andre
Nuernberg, Bernd
Sans, Nathalie
Montcouquiol, Mireille
TI Primary cilium migration depends on G-protein signalling control of
subapical cytoskeleton
SO NATURE CELL BIOLOGY
LA English
DT Article
ID PLANAR CELL POLARITY; BARDET-BIEDL-SYNDROME; HETEROTRIMERIC G-PROTEINS;
INNER-EAR; MICROTUBULE DYNAMICS; MAMMALIAN COCHLEA; PAR PROTEINS;
POLARIZATION; EXPRESSION; CILIARY
AB In ciliated mammalian cells, the precise migration of the primary cilium at the apical surface of the cells, also referred to as translational polarity, defines planar cell polarity (PCP) in very early stages. Recent research has revealed a co-dependence between planar polarization of some cell types and cilium positioning at the surface of cells. This important role of the primary cilium in mammalian cells is in contrast with its absence from Drosophila melanogaster PCP establishment. Here, we show that deletion of GTP-binding protein alpha-i subunit 3 (G alpha(i3)) and mammalian Partner of inscuteable (mPins) disrupts the migration of the kinocilium at the surface of cochlear hair cells and affects hair bundle orientation and shape. Inhibition of G-protein function in vitro leads to kinocilium migration defects, PCP phenotype and abnormal hair bundle morphology. We show that G alpha(i3)/mPins are expressed in an apical and distal asymmetrical domain, which is opposite and complementary to an aPKC/Par-3/Par-6b expression domain, and non-overlapping with the core PCP protein Vangl2. Thus G-protein-dependent signalling controls the migration of the cilium cell autonomously, whereas core PCP signalling controls long-range tissue PCP.
C1 [Ezan, Jerome; Lasvaux, Lea; Gezer, Aysegul; Sans, Nathalie; Montcouquiol, Mireille] INSERM, Planar Polar & Plast Grp, Neuroctr Magendie, F-33077 Bordeaux, France.
[Ezan, Jerome; Lasvaux, Lea; Gezer, Aysegul; Sans, Nathalie; Montcouquiol, Mireille] Univ Bordeaux, Neuroctr Magendie, F-33077 Bordeaux, France.
[Novakovic, Ana; Beer-Hammer, Sandra; Nuernberg, Bernd] Univ Tubingen, Dept Pharmacol & Expt Therapy, Inst Expt & Clin Pharmacol & Toxicol, Eberhard Karls Univ Hosp & Clin, D-72074 Tubingen, Germany.
[Novakovic, Ana; Beer-Hammer, Sandra; Nuernberg, Bernd] Univ Tubingen, Interfac Ctr Pharmacogen & Drug Res, D-72074 Tubingen, Germany.
[May-Simera, Helen] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
[Belotti, Edwige; Lhoumeau, Anne-Catherine; Borg, Jean-Paul] CRCM, INSERM, U1068, F-13009 Marseille, France.
[Belotti, Edwige; Lhoumeau, Anne-Catherine; Borg, Jean-Paul] CRCM, CNRS, UMR7258, F-13009 Marseille, France.
[Belotti, Edwige; Lhoumeau, Anne-Catherine; Borg, Jean-Paul] Inst J Paoli I Calmettes, F-13009 Marseille, France.
[Belotti, Edwige; Lhoumeau, Anne-Catherine; Borg, Jean-Paul] Aix Marseille Univ, F-13007 Marseille, France.
[Birnbaumer, Lutz] NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, Durham, NC 27709 USA.
[Le Bivic, Andre] CNRS, UMR 7288, IBDML, F-13288 Marseille 09, France.
[Le Bivic, Andre] Aix Marseille Univ, IBDML, F-13288 Marseille, France.
RP Montcouquiol, M (reprint author), INSERM, Planar Polar & Plast Grp, Neuroctr Magendie, F-33077 Bordeaux, France.
EM mireille.montcouquiol@inserm.fr
RI Beer-Hammer, Sandra/C-7442-2014;
OI montcouquiol, mireille/0000-0001-8739-6519
FU INSEAM; Conseil Regional d'Aquitaine Neurocampus program; La Fondation
pour la Recherche Medicale; European Commission Coordination Action
ENINET [LSHM-CT-2005-19063]; Ligue Nationale Contre le Cancer; EUCAAD;
Fondation ARC pour la Recherche sur le Cancer; Deutsche
Forschungsgemeinschaft (DFG); Intramural Research Program of the NIH
[Z01-ES-101643]; European FP7 program [HEALTH-F2-2008-200234]; ANR
[BLAN07-2-186738]; [ANR-08-MNPS-040-01]
FX We thank the animal and genotyping facilities' members of the
Neurocentre for technical assistance, notably H. Doat and D. Gonzales.
We also thank the entire team of the Bordeaux Imaging Center (BIC) for
the constant technical assistance, notably P. Legros, S. Marais and C.
Poujol. We thank P. Beales (UCL, UK) for the Mkks mutants. We thank L.
Mays (Tubingen, Germany) for critical reading of the manuscript, and F.
Schweisguth (Paris, France) and J. Raff (Oxford, UK) for thoughtful
discussions. We apologize to all whose relevant work could not be cited.
This research was supported by an INSEAM grant to M.M. and N.S., the
Conseil Regional d'Aquitaine Neurocampus program, La Fondation pour la
Recherche Medicale (M.M., N.S., J.E., A-C.L.), ANR-08-MNPS-040-01
(M.M.), the European Commission Coordination Action ENINET
(LSHM-CT-2005-19063; N.S. and M.M.), Ligue Nationale Contre le Cancer
(Label 2010, J-P.B.), EUCAAD (FP7 program, J-P.B.), Fondation ARC pour
la Recherche sur le Cancer (B.N., E.B.), the Deutsche
Forschungsgemeinschaft (DFG; B.N., S.B-H.), the Intramural Research
Program of the NIH (Project Z01-ES-101643 to L.B.), the European FP7
program (HEALTH-F2-2008-200234, A.L.B.) and ANR (BLAN07-2-186738,
A.L.B.).
NR 39
TC 36
Z9 37
U1 0
U2 16
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1465-7392
J9 NAT CELL BIOL
JI Nat. Cell Biol.
PD SEP
PY 2013
VL 15
IS 9
BP 1107
EP +
DI 10.1038/ncb2819
PG 17
WC Cell Biology
SC Cell Biology
GA 213IP
UT WOS:000324050000011
PM 23934215
ER
PT J
AU Iyer, LM
Zhang, DP
Burroughs, AM
Aravind, L
AF Iyer, Lakshminarayan M.
Zhang, Dapeng
Burroughs, A. Maxwell
Aravind, L.
TI Computational identification of novel biochemical systems involved in
oxidation, glycosylation and other complex modifications of bases in DNA
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID TRANSFER-RNA; ESCHERICHIA-COLI; COMPARATIVE GENOMICS; NATURAL-HISTORY;
TET PROTEINS; ALPHA-PUTRESCINYLTHYMINE; STRUCTURE PREDICTION;
CRYSTAL-STRUCTURE; MODIFYING ENZYME; BINDING DOMAINS
AB Discovery of the TET/JBP family of dioxygenases that modify bases in DNA has sparked considerable interest in novel DNA base modifications and their biological roles. Using sensitive sequence and structure analyses combined with contextual information from comparative genomics, we computationally characterize over 12 novel biochemical systems for DNA modifications. We predict previously unidentified enzymes, such as the kinetoplastid J-base generating glycosyltransferase (and its homolog GREB1), the catalytic specificity of bacteriophage TET/JBP proteins and their role in complex DNA base modifications. We also predict the enzymes involved in synthesis of hypermodified bases such as alpha-glutamylthymine and alphaputrescinylthymine that have remained enigmatic for several decades. Moreover, the current analysis suggests that bacteriophages and certain nucleo-cytoplasmic large DNA viruses contain an unexpectedly diverse range of DNA modification systems, in addition to those using previously characterized enzymes such as Dam, Dcm, TET/JBP, pyrimidine hydroxymethylases, Mom and glycosyltransferases. These include enzymes generating modified bases such as deazaguanines related to queuine and archaeosine, pyrimidines comparable with lysidine, those derived using modified S-adenosyl methionine derivatives and those using TET/JBP-generated hydroxymethyl pyrimidines as biosynthetic starting points. We present evidence that some of these modification systems are also widely dispersed across prokaryotes and certain eukaryotes such as basidiomycetes, chlorophyte and stramenopile alga, where they could serve as novel epigenetic marks for regulation or discrimination of self from non-self DNA. Our study extends the role of the PUA-like fold domains in recognition of modified nucleic acids and predicts versions of the ASCH and EVE domains to be novel 'readers' of modified bases in DNA. These results open opportunities for the investigation of the biology of these systems and their use in biotechnology.
C1 [Iyer, Lakshminarayan M.; Zhang, Dapeng; Burroughs, A. Maxwell; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM aravind@ncbi.nlm.nih.gov
FU US Department of Health and Human Services (National Library of
Medicine, National Institutes of Health (NIH)); NIH
FX Intramural funds of the US Department of Health and Human Services
(National Library of Medicine, National Institutes of Health (NIH)).
Funding for open access charge: The intra-mural funds of the NIH.
NR 118
TC 26
Z9 26
U1 1
U2 26
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD SEP
PY 2013
VL 41
IS 16
BP 7635
EP 7655
DI 10.1093/nar/gkt573
PG 21
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 228GG
UT WOS:000325173300014
PM 23814188
ER
PT J
AU Huang, SYN
Murai, J
Dalla Rosa, I
Dexheimer, TS
Naumova, A
Gmeiner, WH
Pommier, Y
AF Huang, Shar-yin N.
Murai, Junko
Dalla Rosa, Ilaria
Dexheimer, Thomas S.
Naumova, Alena
Gmeiner, William H.
Pommier, Yves
TI TDP1 repairs nuclear and mitochondrial DNA damage induced by
chain-terminating anticancer and antiviral nucleoside analogs
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID STRAND BREAK REPAIR; I CLEAVAGE COMPLEXES; TOPOISOMERASE-I;
PHOSPHODIESTERASE TDP1; SPINOCEREBELLAR ATAXIA; ARA-C; DIFFERENTIAL
INCORPORATION; AXONAL NEUROPATHY; POLYMERASE; CELLS
AB Chain-terminating nucleoside analogs (CTNAs) that cause stalling or premature termination of DNA replication forks are widely used as anticancer and antiviral drugs. However, it is not well understood how cells repair the DNA damage induced by these drugs. Here, we reveal the importance of tyrosyl-DNA phosphodiesterase 1 (TDP1) in the repair of nuclear and mitochondrial DNA damage induced by CTNAs. On investigating the effects of four CTNAs-acyclovir (ACV), cytarabine (Ara-C), zidovudine (AZT) and zalcitabine (ddC)-we show that TDP1 is capable of removing the covalently linked corresponding CTNAs from DNA 3'-ends. We also show that Tdp1(-/-) cells are hypersensitive and accumulate more DNA damage when treated with ACV and Ara-C, implicating TDP1 in repairing CTNA-induced DNA damage. As AZT and ddC are known to cause mitochondrial dysfunction, we examined whether TDP1 repairs the mitochondrial DNA damage they induced. We find that AZT and ddC treatment leads to greater depletion of mitochondrial DNA in Tdp1(-/-) cells. Thus, TDP1 seems to be critical for repairing nuclear and mitochondrial DNA damage caused by CTNAs.
C1 [Huang, Shar-yin N.; Murai, Junko; Dalla Rosa, Ilaria; Naumova, Alena; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Murai, Junko] Kyoto Univ, Grad Sch Med, Dept Radiat Genet, Sakyo Ku, Kyoto 6068501, Japan.
[Dexheimer, Thomas S.] NIH, NIH Chem Genom Ctr, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
[Gmeiner, William H.] Wake Forest Sch Med, Dept Canc Biol, Winston Salem, NC 27157 USA.
RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM pommier@nih.gov
FU Intramural Program of the National Cancer Institute, Center for Cancer
Research [Z01 BC006150]; NIH-NCI [U01 CA102532]
FX Intramural Program of the National Cancer Institute, Center for Cancer
Research [Z01 BC006150]; NIH-NCI [U01 CA102532]. Funding for open access
charge: Intramural Program of the National Cancer Institute, Center for
Cancer Research [Z01 BC006150].
NR 55
TC 27
Z9 28
U1 0
U2 16
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD SEP
PY 2013
VL 41
IS 16
BP 7793
EP 7803
DI 10.1093/nar/gkt483
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 228GG
UT WOS:000325173300026
PM 23775789
ER
PT J
AU Zhuang, R
Rao, JN
Zou, TT
Liu, L
Xiao, L
Cao, S
Hansraj, NZ
Gorospe, M
Wang, JY
AF Zhuang, Ran
Rao, Jaladanki N.
Zou, Tongtong
Liu, Lan
Xiao, Lan
Cao, Shan
Hansraj, Natasha Z.
Gorospe, Myriam
Wang, Jian-Ying
TI miR-195 competes with HuR to modulate stim1 mRNA stability and regulate
cell migration
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID BINDING PROTEIN HUR; INTESTINAL EPITHELIAL RESTITUTION; OPERATED CA2+
CHANNEL; DEPENDENT KINASE 4; PLASMA-MEMBRANE; SUPPRESSES TUMORIGENICITY;
HEPATOCELLULAR-CARCINOMA; TRANSLATIONAL CONTROL; COMPETITIVE-BINDING;
MUCOSAL RESTITUTION
AB Stromal interaction molecule 1 (Stim1) functions as a sensor of Ca2+ within stores and plays an essential role in the activation of store-operated Ca2+ entry (SOCE). Although lowering Stim1 levels reduces store-operated Ca2+ entry and inhibits intestinal epithelial repair after wounding, the mechanisms that control Stim1 expression remain unknown. Here, we show that cellular Stim1 abundance is controlled posttranscriptionally via factors that associate with 3'-untranslated region (3'-UTR) of stim1 mRNA. MicroRNA-195 (miR-195) and the RNA-binding protein HuR competed for association with the stim1 3'-UTR and regulated stim1 mRNA decay in opposite directions. Interaction of miR-195 with the stim1 3'-UTR destabilized stim1 mRNA, whereas the stability of stim1 mRNA increased with HuR association. Interestingly, ectopic miR-195 overexpression enhanced stim1 mRNA association with argonautecontaining complexes and increased the colocalization of tagged stim1 RNA with processing bodies (P-bodies); the translocation of stim1 mRNA was abolished by HuR overexpression. Moreover, decreased levels of Stim1 by miR-195 overexpression inhibited cell migration over the denuded area after wounding but was rescued by increasing HuR levels. In sum, Stim1 expression is controlled by two factors competing for influence on stim1 mRNA stability: the mRNA-stabilizing protein HuR and the decay-promoting miR-195.
C1 [Zhuang, Ran; Rao, Jaladanki N.; Zou, Tongtong; Liu, Lan; Xiao, Lan; Cao, Shan; Hansraj, Natasha Z.; Wang, Jian-Ying] Univ Maryland, Sch Med, Dept Surg, Cell Biol Grp, Baltimore, MD 21201 USA.
[Zhuang, Ran; Rao, Jaladanki N.; Zou, Tongtong; Liu, Lan; Xiao, Lan; Cao, Shan; Hansraj, Natasha Z.; Wang, Jian-Ying] Baltimore Vet Affairs Med Ctr, Baltimore, MD 21201 USA.
[Wang, Jian-Ying] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA.
[Gorospe, Myriam] NIA, Genet Lab, IRP, NIH, Baltimore, MD 21224 USA.
RP Wang, JY (reprint author), Univ Maryland, Sch Med, Dept Surg, Cell Biol Grp, Baltimore, MD 21201 USA.
EM jwang@smail.umaryland.edu
FU US Department of Veterans Affairs; National Institutes of Health (NIH)
[DK57819, DK61972, DK68491]; National Institute on Aging-Intramural
Research Program, NIH; National Institute of Diabetes and Digestive and
Kidney Diseases
FX Merit Review Grants (to J-Y.W. and J.N.R.) from US Department of
Veterans Affairs and from National Institutes of Health (NIH) [DK57819,
DK61972, DK68491 to J-Y.W.]; National Institute on Aging-Intramural
Research Program, NIH (to M.G.). Funding for open access charge:
National Institute of Diabetes and Digestive and Kidney Diseases.
NR 66
TC 30
Z9 30
U1 0
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD SEP
PY 2013
VL 41
IS 16
BP 7905
EP 7919
DI 10.1093/nar/gkt565
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 228GG
UT WOS:000325173300035
PM 23804758
ER
PT J
AU Cho, DY
Przytycka, TM
AF Cho, Dong-Yeon
Przytycka, Teresa M.
TI Dissecting cancer heterogeneity with a probabilistic genotype-phenotype
model
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID CLINICALLY RELEVANT SUBTYPES; PATTERN DISCOVERY; GENE-EXPRESSION;
GENOMIC DATA; GLIOBLASTOMA; NETWORKS; PATHWAYS; BREAST
AB One of the obstacles hindering a better understanding of cancer is its heterogeneity. However, computational approaches to model cancer heterogeneity have lagged behind. To bridge this gap, we have developed a new probabilistic approach that models individual cancer cases as mixtures of subtypes. Our approach can be seen as a meta-model that summarizes the results of a large number of alternative models. It does not assume predefined subtypes nor does it assume that such subtypes have to be sharply defined. Instead given a measure of phenotypic similarity between patients and a list of potential explanatory features, such as mutations, copy number variation, microRNA levels, etc., it explains phenotypic similarities with the help of these features. We applied our approach to Glioblastoma Multiforme (GBM). The resulting model Prob_GBM, not only correctly inferred known relationships but also identified new properties underlining phenotypic similarities. The proposed probabilistic framework can be applied to model relations between similarity of gene expression and a broad spectrum of potential genetic causes.
C1 [Cho, Dong-Yeon; Przytycka, Teresa M.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Przytycka, TM (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM przytyck@ncbi.nlm.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Library of Medicine
FX Funding for open access charge: Intramural Research Program of the
National Institutes of Health, National Library of Medicine.
NR 37
TC 6
Z9 6
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD SEP
PY 2013
VL 41
IS 17
BP 8011
EP 8020
DI 10.1093/nar/gkt577
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 228HF
UT WOS:000325175900010
PM 23821670
ER
PT J
AU Eun, B
Sampley, ML
Van Winkle, MT
Good, AL
Kachman, MM
Pfeifer, K
AF Eun, Bokkee
Sampley, Megan L.
Van Winkle, Matthew T.
Good, Austin L.
Kachman, Marika M.
Pfeifer, Karl
TI The Igf2/H19 muscle enhancer is an active transcriptional complex
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID TISSUE-SPECIFIC ENHANCERS; NONCODING RNAS; HUMAN GENOME;
GENE-TRANSCRIPTION; X-CHROMOSOME; HUMAN-CELLS; PROMOTERS; LOCUS;
METHYLATIONS; COACTIVATOR
AB In eukaryotic cells, gene expression is mediated by enhancer activation of RNA polymerase at distant promoters. Recently, distinctions between enhancers and promoters have been blurred by the discovery that enhancers are associated with RNA polymerase and are sites of RNA synthesis. Here, we present an analysis of the insulin-like growth factor 2/H19 muscle enhancer. This enhancer includes a short conserved core element that is organized into chromatin typical of mammalian enhancers, binds tissue-specific transcription factors and functions on its own in vitro to activate promoter transcription. However, in a chromosomal context, this element is not sufficient to activate distant promoters. Instead, enhancer function also requires transcription in cis of a long non-coding RNA, Nctc1. Thus, the insulin-like growth factor 2/H19 enhancer is an active transcriptional complex whose own transcription is essential to its function.
C1 [Eun, Bokkee; Sampley, Megan L.; Van Winkle, Matthew T.; Good, Austin L.; Kachman, Marika M.; Pfeifer, Karl] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
[Eun, Bokkee] Korea Univ, Coll Med, Core Lab, Seoul 136701, South Korea.
RP Pfeifer, K (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
EM pfeiferk@mail.nih.gov
OI Pfeifer, Karl/0000-0002-0254-682X
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD), Division of Intramural Research [1ZIAHD001804]
FX Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD), Division of Intramural Research [1ZIAHD001804].
Funding for open access charge: Eunice Kennedy Shriver NICHD Division of
Intramural Research [1ZIAHD001804].
NR 48
TC 9
Z9 10
U1 0
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD SEP
PY 2013
VL 41
IS 17
BP 8126
EP 8134
DI 10.1093/nar/gkt597
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 228HF
UT WOS:000325175900019
PM 23842673
ER
PT J
AU Nagarajavel, V
Iben, JR
Howard, BH
Maraia, RJ
Clark, DJ
AF Nagarajavel, V.
Iben, James R.
Howard, Bruce H.
Maraia, Richard J.
Clark, David J.
TI Global 'bootprinting' reveals the elastic architecture of the yeast
TFIIIB-TFIIIC transcription complex in vivo
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID RNA-POLYMERASE-III; SACCHAROMYCES-CEREVISIAE; BUDDING YEAST; READ
ALIGNMENT; FISSION YEAST; GENES; NUCLEOSOME; GENOME; LOCALIZATION;
CHROMATIN
AB TFIIIB and TFIIIC are multi-subunit factors required for transcription by RNA polymerase III. We present a genome-wide high-resolution footprint map of TFIIIB-TFIIIC complexes in Saccharomyces cerevisiae, obtained by paired-end sequencing of micrococcal nuclease-resistant DNA. On tRNA genes, TFIIIB and TFIIIC form stable complexes with the same distinctive occupancy pattern but in mirror image, termed 'bootprints'. Global analysis reveals that the TFIIIB-TFIIIC transcription complex exhibits remarkable structural elasticity: tRNA genes vary significantly in length but remain protected by TFIIIC. Introns, when present, are markedly less protected. The RNA polymerase III transcription terminator is flexibly accommodated within the transcription complex and, unexpectedly, plays a major structural role by delimiting its 3'-boundary. The ETC sites, where TFIIIC binds without TFIIIB, exhibit different bootprints, suggesting that TFIIIC forms complexes involving other factors. We confirm six ETC sites and report a new site (ETC10). Surprisingly, TFIIIC, but not TFIIIB, interacts with some centromeric nucleosomes, suggesting that interactions between TFIIIC and the centromere may be important in the 3D organization of the nucleus.
C1 [Nagarajavel, V.; Iben, James R.; Howard, Bruce H.; Maraia, Richard J.; Clark, David J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD USA.
RP Clark, DJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD USA.
EM maraiar@mail.nih.gov; clarkda@mail.nih.gov
FU Intramural Research program of the NIH (NICHD); National Institutes of
Health Intramural Program (NICHD)
FX Intramural Research program of the NIH (NICHD). Funding for open access
charge: National Institutes of Health Intramural Program (NICHD).
NR 46
TC 21
Z9 21
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD SEP
PY 2013
VL 41
IS 17
BP 8135
EP 8143
DI 10.1093/nar/gkt611
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 228HF
UT WOS:000325175900020
PM 23856458
ER
PT J
AU Kazemian, M
Pham, H
Wolfe, SA
Brodsky, MH
Sinha, S
AF Kazemian, Majid
Pham, Hannah
Wolfe, Scot A.
Brodsky, Michael H.
Sinha, Saurabh
TI Widespread evidence of cooperative DNA binding by transcription factors
in Drosophila development
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID PROTEIN-PROTEIN INTERACTIONS; GAGA FACTOR; COLLABORATIVE COMPETITION;
INTERACTOME NETWORK; CHROMATIN-STRUCTURE; GENE-EXPRESSION; REGULATORY
CODE; GLOBAL ANALYSIS; INTERACTION MAP; PARTNER CODE
AB Regulation of eukaryotic gene transcription is often combinatorial in nature, with multiple transcription factors (TFs) regulating common target genes, often through direct or indirect mutual interactions. Many individual examples of cooperative binding by directly interacting TFs have been identified, but it remains unclear how pervasive this mechanism is during animal development. Cooperative TF binding should be manifest in genomic sequences as biased arrangements of TF-binding sites. Here, we explore the extent and diversity of such arrangements related to gene regulation during Drosophila embryogenesis. We used the DNA-binding specificities of 322 TFs along with chromatin accessibility information to identify enriched spacing and orientation patterns of TF-binding site pairs. We developed a new statistical approach for this task, specifically designed to accurately assess inter-site spacing biases while accounting for the phenomenon of homotypic site clustering commonly observed in developmental regulatory regions. We observed a large number of short-range distance preferences between TF-binding site pairs, including examples where the preference depends on the relative orientation of the binding sites. To test whether these binding site patterns reflect physical interactions between the corresponding TFs, we analyzed 27 TF pairs whose binding sites exhibited short distance preferences. In vitro protein-protein binding experiments revealed that > 65% of these TF pairs can directly interact with each other. For five pairs, we further demonstrate that they bind cooperatively to DNA if both sites are present with the preferred spacing. This study demonstrates how DNA-binding motifs can be used to produce a comprehensive map of sequence signatures for different mechanisms of combinatorial TF action.
C1 [Kazemian, Majid; Sinha, Saurabh] Univ Illinois, Dept Comp Sci, Urbana, IL USA.
[Kazemian, Majid] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD USA.
[Kazemian, Majid] NHLBI, Ctr Immunol, NIH, Bethesda, MD USA.
[Pham, Hannah; Wolfe, Scot A.; Brodsky, Michael H.] Univ Massachusetts, Program Gene Funct & Express, Sch Med, Amherst, MA 01003 USA.
[Wolfe, Scot A.] Univ Massachusetts, Dept Biochem & Mol Pharmacol, Sch Med, Amherst, MA 01003 USA.
[Brodsky, Michael H.] Univ Massachusetts, Dept Mol Med, Sch Med, Amherst, MA 01003 USA.
[Sinha, Saurabh] Univ Illinois, Inst Genom Biol, Urbana, IL USA.
RP Sinha, S (reprint author), Univ Illinois, Dept Comp Sci, Urbana, IL USA.
EM Michael.brodsky@umassmed.edu; sinhas@illinois.edu
OI Kazemian, Majid/0000-0001-7080-8820
FU National Institutes of Health (NIH) [GM085233]; National Science
Foundation [DBI-0746303]; National Human Genome Research Institute of
the NIH [R01 HG004744-01]
FX Funding for open access charge: National Institutes of Health (NIH)
[GM085233]; National Science Foundation [DBI-0746303 to S.S.]; National
Human Genome Research Institute of the NIH [R01 HG004744-01 to M.H.B.
and S.A.W.].
NR 78
TC 24
Z9 24
U1 0
U2 15
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD SEP
PY 2013
VL 41
IS 17
BP 8237
EP 8252
DI 10.1093/nar/gkt598
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 228HF
UT WOS:000325175900027
PM 23847101
ER
PT J
AU Shuga, J
Zeng, Y
Novak, R
Lan, Q
Tang, XJ
Rothman, N
Vermeulen, R
Li, LY
Hubbard, A
Zhang, LP
Mathies, RA
Smith, MT
AF Shuga, Joe
Zeng, Yong
Novak, Richard
Lan, Qing
Tang, Xiaojiang
Rothman, Nathaniel
Vermeulen, Roel
Li, Laiyu
Hubbard, Alan
Zhang, Luoping
Mathies, Richard A.
Smith, Martyn T.
TI Single molecule quantitation and sequencing of rare translocations using
microfluidic nested digital PCR
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID MINIMAL RESIDUAL DISEASE; FOLLICULAR LYMPHOMA; HEALTHY-INDIVIDUALS;
CHROMOSOMAL BREAKPOINT; CARRYING CELLS; DNA; T(14/18); MUTATIONS;
EXPOSURE; LEUKEMIA
AB Cancers are heterogeneous and genetically unstable. New methods are needed that provide the sensitivity and specificity to query single cells at the genetic loci that drive cancer progression, thereby enabling researchers to study the progression of individual tumors. Here, we report the development and application of a bead-based hemi-nested microfluidic droplet digital PCR (dPCR) technology to achieve 'quantitative' measurement and single-molecule sequencing of somatically acquired carcinogenic translocations at extremely low levels (<10(-6)) in healthy subjects. We use this technique in our healthy study population to determine the overall concentration of the t(14;18) translocation, which is strongly associated with follicular lymphoma. The nested dPCR approach improves the detection limit to 1 x 10(-7) or lower while maintaining the analysis efficiency and specificity. Further, the bead-based dPCR enabled us to isolate and quantify the relative amounts of the various clonal forms of t(14; 18) translocation in these subjects, and the single-molecule sensitivity and resolution of dPCR led to the discovery of new clonal forms of t(14; 18) that were otherwise masked by the conventional quantitative PCR measurements. In this manner, we created a quantitative map for this carcinogenic mutation in this healthy population and identified the positions on chromosomes 14 and 18 where the vast majority of these t(14; 18) events occur.
C1 [Shuga, Joe; Hubbard, Alan; Zhang, Luoping; Smith, Martyn T.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA.
[Zeng, Yong; Mathies, Richard A.] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
[Zeng, Yong] Univ Kansas, Dept Chem, Lawrence, KS 66045 USA.
[Novak, Richard; Mathies, Richard A.] Univ Calif Berkeley, UC San Francisco UC Berkeley Grad Program Bioengn, Berkeley, CA 94720 USA.
[Lan, Qing; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20852 USA.
[Tang, Xiaojiang; Li, Laiyu] Guangdong Poison Control Ctr, Guangzhou 510300, Guangdong, Peoples R China.
[Vermeulen, Roel] Univ Utrecht, Environm Epidemiol Div, Inst Risk Assessment Sci, NL-3508 Utrecht, Netherlands.
RP Smith, MT (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA.
EM martynts@berkeley.edu
FU Trans-National Institutes of Health Genes, Environment and Health
Initiative, Biological Response Indicators of Environmental Systems
Center Grant [U54 ES016115-01]; National Institute of Environmental
Health Sciences Superfund Basic Research Program [P42 ES004705]; Canary
Foundation; American Cancer Society [116373-PFTED-08-251-01-SIED];
University of Kansas; National Science Foundation Graduate Research
Fellowship; National Institutes of Health [U54 ES016115-01]
FX Trans-National Institutes of Health Genes, Environment and Health
Initiative, Biological Response Indicators of Environmental Systems
Center Grant [U54 ES016115-01 to M. T. S. and R. A. M.] and National
Institute of Environmental Health Sciences Superfund Basic Research
Program Grant [P42 ES004705 to M. T. S.]; Canary Foundation and ACS
Postdoctoral Fellowship Award in Early Detection
[116373-PFTED-08-251-01-SIED to J.S.] from the American Cancer Society;
New faculty start-up funds from the University of Kansas (in part to
Y.Z.). National Science Foundation Graduate Research Fellowship (to
R.N.). Funding for open access charge: National Institutes of Health
[U54 ES016115-01].
NR 42
TC 17
Z9 18
U1 2
U2 63
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD SEP
PY 2013
VL 41
IS 16
AR e159
DI 10.1093/nar/gkt613
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 228GG
UT WOS:000325173300007
PM 23873959
ER
PT J
AU Blanch-Hartigan, D
Ruben, MA
AF Blanch-Hartigan, Danielle
Ruben, Mollie A.
TI Training clinicians to accurately perceive their patients: Current state
and future directions
SO PATIENT EDUCATION AND COUNSELING
LA English
DT Article; Proceedings Paper
CT International Conference on Communication in Healthcare (ICCH)
CY 2012
CL Univ St Andrews, Med Sch, St Andrews, SCOTLAND
SP European Assoc Commun Healthcare
HO Univ St Andrews, Med Sch
DE Training; Person perception accuracy; Medical education; Emotion
recognition; Patient-centered care
ID IMPROVE PHYSICIANS DETECTION; MEDICAL-STUDENTS; NONVERBAL-COMMUNICATION;
INTERPERSONAL SKILLS; EMOTION RECOGNITION; DETECTING DECEPTION; FACIAL
EXPRESSIONS; SEQUENCE-ANALYSIS; SELF-ASSESSMENT; CANCER-PATIENTS
AB Objective: To review the literature on training clinicians' person perception accuracy, or the ability to correctly judge patients' states and traits. To present the importance of training this skill, share evidence it is a trainable skill, and suggest evidence-based recommendations for implementing training.
Methods: We conducted a literature review on person perception training studies developed for or implemented with clinicians. We also summarized measures to evaluate training efficacy, barriers to implementation, and future research directions.
Results: Training studies exist to improve clinicians' ability to perceive patients' emotions, pain, distress, and depression. These varied in training approach, length of training, and study design. Ten of 13 studies showed training benefited person perception accuracy.
Conclusions: The medical literature and previous meta-analysis on person perception training across contexts demonstrate that training person perception accuracy can be effective. Examples of effective trainings provide suggestions of best-practices for future efforts in this area.
Practice implications: More evidence is needed to create and implement trainings which produce not only differences in accuracy but also in patient care and outcomes. Medical curriculum developers and researchers should collaborate to create effective person perception trainings for clinicians. Published by Elsevier Ireland Ltd.
C1 [Blanch-Hartigan, Danielle] NCI, Div Canc Control & Populat Sci, Off Canc Survivorship, Bethesda, MD 20892 USA.
[Ruben, Mollie A.] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA.
RP Blanch-Hartigan, D (reprint author), NCI, Off Canc Survivorship, 6116 Execut Blvd,Suite 404,MSC 8336, Rockville, MD 20892 USA.
EM danielleblanch@gmail.com
OI Ruben, Mollie/0000-0001-8918-8932
NR 67
TC 8
Z9 8
U1 3
U2 17
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0738-3991
J9 PATIENT EDUC COUNS
JI Patient Educ. Couns.
PD SEP
PY 2013
VL 92
IS 3
SI SI
BP 328
EP 336
DI 10.1016/j.pec.2013.02.010
PG 9
WC Public, Environmental & Occupational Health; Social Sciences,
Interdisciplinary
SC Public, Environmental & Occupational Health; Social Sciences - Other
Topics
GA 221KM
UT WOS:000324657800008
PM 23490175
ER
PT J
AU Gallaher, AM
Das, S
Xiao, Z
Andresson, T
Kieffer-Kwon, P
Happel, C
Ziegelbauer, J
AF Gallaher, Amelia M.
Das, Sudipto
Xiao, Zhen
Andresson, Thorkell
Kieffer-Kwon, Philippe
Happel, Christine
Ziegelbauer, Joseph
TI Proteomic Screening of Human Targets of Viral microRNAs Reveals
Functions Associated with Immune Evasion and Angiogenesis
SO PLOS PATHOGENS
LA English
DT Article
ID SARCOMA-ASSOCIATED HERPESVIRUS; NF-KAPPA-B; INFLAMMATORY-CYTOKINE
EXPRESSION; HUMAN GAMMA-HERPESVIRUSES; VIRUS-ENCODED MICRORNAS; HUMAN
ENDOTHELIAL-CELLS; HEME OXYGENASE-1; GENE-TRANSFER; PROTEIN-SYNTHESIS;
UBIQUITIN LIGASE
AB Kaposi's sarcoma (KS) is caused by infection with Kaposi's sarcoma-associated herpesvirus (KSHV). The virus expresses unique microRNAs (miRNAs), but the targets and functions of these miRNAs are not completely understood. In order to identify human targets of viral miRNAs, we measured protein expression changes caused by multiple KSHV miRNAs using pulsed stable labeling with amino acids in cell culture (pSILAC) in primary endothelial cells. This led to the identification of multiple human genes that are repressed at the protein level, but not at the miRNA level. Further analysis also identified that KSHV miRNAs can modulate activity or expression of upstream regulatory factors, resulting in suppressed activation of a protein involved in leukocyte recruitment (ICAM1) following lysophosphatidic acid treatment, as well as up-regulation of a pro-angiogenic protein (HIF1 alpha), and up-regulation of a protein involved in stimulating angiogenesis (HMOX1). This study aids in our understanding of miRNA mechanisms of repression and miRNA contributions to viral pathogenesis.
C1 [Gallaher, Amelia M.; Kieffer-Kwon, Philippe; Happel, Christine; Ziegelbauer, Joseph] NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA.
[Das, Sudipto; Xiao, Zhen; Andresson, Thorkell] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
RP Gallaher, AM (reprint author), NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA.
EM ziegelbauerjm@mail.nih.gov
OI Ziegelbauer, Joseph/0000-0001-6464-6941
FU Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health; National Cancer
Institute [HHSN261200800001E]
FX This work was supported by the Intramural Research Program of the Center
for Cancer Research, National Cancer Institute, National Institutes of
Health and with federal funds from the National Cancer Institute under
Contract HHSN261200800001E. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 58
TC 16
Z9 16
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD SEP
PY 2013
VL 9
IS 9
AR e1003584
DI 10.1371/journal.ppat.1003584
PG 14
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 224WM
UT WOS:000324922300014
PM 24039573
ER
PT J
AU Garver, LS
Oliveira, GD
Barillas-Mury, C
AF Garver, Lindsey S.
Oliveira, Giselle de Almeida
Barillas-Mury, Carolina
TI The JNK Pathway Is a Key Mediator of Anopheles gambiae Antiplasmodial
Immunity
SO PLOS PATHOGENS
LA English
DT Article
ID NF-KAPPA-B; SMOOTH-MUSCLE-CELLS; PLASMODIUM-BERGHEI; SIGNALING PATHWAYS;
MALARIA PARASITE; MIDGUT CELLS; DROSOPHILA; INFECTION; ACTIVATION;
MOSQUITOS
AB The innate immune system of Anopheles gambiae mosquitoes limits Plasmodium infection through multiple molecular mechanisms. For example, midgut invasion by the parasite triggers an epithelial nitration response that promotes activation of the complement-like system. We found that suppression of the JNK pathway, by silencing either Hep, JNK, Jun or Fos expression, greatly enhanced Plasmodium infection; while overactivating this cascade, by silencing the suppressor Puckered, had the opposite effect. The JNK pathway limits infection via two coordinated responses. It induces the expression of two enzymes (HPx2 and NOX5) that potentiate midgut epithelial nitration in response to Plasmodium infection and regulates expression of two key hemocyte-derived immune effectors (TEP1 and FBN9). Furthermore, the An. gambiae L3-5 strain that has been genetically selected to be refractory (R) to Plasmodium infection exhibits constitutive overexpression of genes from the JNK pathway, as well as midgut and hemocyte effector genes. Silencing experiments confirmed that this cascade mediates, to a large extent, the drastic parasite elimination phenotype characteristic of this mosquito strain. In sum, these studies revealed the JNK pathway as a key regulator of the ability of An. gambiae mosquitoes to limit Plasmodium infection and identified several effector genes mediating these responses.
C1 [Garver, Lindsey S.; Oliveira, Giselle de Almeida; Barillas-Mury, Carolina] Natl Inst Hlth, Natl Inst Allergy & Infect Dis, Lab Malaria & Vector Res, Rockville, MD USA.
RP Garver, LS (reprint author), Natl Inst Hlth, Natl Inst Allergy & Infect Dis, Lab Malaria & Vector Res, Rockville, MD USA.
EM cbarillas@niaid.nih.gov
OI Oliveira, Giselle/0000-0002-5898-7843; Garver,
Lindsey/0000-0003-2893-0130
FU Intramural Research Program of the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health; Malaria Infection Biology Research and Training
Program, NIAID, NIH
FX This work was supported by the Intramural Research Program of the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health. LSG received funding
from the Malaria Infection Biology Research and Training Program, NIAID,
NIH. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 40
TC 32
Z9 33
U1 0
U2 12
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD SEP
PY 2013
VL 9
IS 9
AR e1003622
DI 10.1371/journal.ppat.1003622
PG 10
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 224WM
UT WOS:000324922300036
PM 24039583
ER
PT J
AU Huijben, S
Bell, AS
Sim, DG
Tomasello, D
Mideo, N
Day, T
Read, AF
AF Huijben, Silvie
Bell, Andrew S.
Sim, Derek G.
Tomasello, Danielle
Mideo, Nicole
Day, Troy
Read, Andrew F.
TI Aggressive Chemotherapy and the Selection of Drug Resistant Pathogens
SO PLOS PATHOGENS
LA English
DT Article
ID COMMUNITY-ACQUIRED PNEUMONIA; MALARIA PARASITES; ANTIBIOTIC-RESISTANCE;
BACTERIAL-MENINGITIS; COMPETITIVE RELEASE; PLASMODIUM-CHABAUDI;
EVOLUTION; POPULATION; DYNAMICS; THERAPY
AB Drug resistant pathogens are one of the key public health challenges of the 21 st century. There is a widespread belief that resistance is best managed by using drugs to rapidly eliminate target pathogens from patients so as to minimize the probability that pathogens acquire resistance de novo. Yet strong drug pressure imposes intense selection in favor of resistance through alleviation of competition with wild-type populations. Aggressive chemotherapy thus generates opposing evolutionary forces which together determine the rate of drug resistance emergence. Identifying treatment regimens which best retard resistance evolution while maximizing health gains and minimizing disease transmission requires empirical analysis of resistance evolution in vivo in conjunction with measures of clinical outcomes and infectiousness. Using rodent malaria in laboratory mice, we found that less aggressive chemotherapeutic regimens substantially reduced the probability of onward transmission of resistance (by.150-fold), without compromising health outcomes. Our experiments suggest that there may be cases where resistance evolution can be managed more effectively with treatment regimens other than those which reduce pathogen burdens as fast as possible.
C1 [Huijben, Silvie; Bell, Andrew S.; Sim, Derek G.; Tomasello, Danielle; Mideo, Nicole; Read, Andrew F.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Huijben, Silvie; Bell, Andrew S.; Sim, Derek G.; Tomasello, Danielle; Mideo, Nicole; Read, Andrew F.] Penn State Univ, Dept Entomol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Day, Troy] Queens Univ, Dept Math, Kingston, ON, Canada.
[Day, Troy] Queens Univ, Dept Stat, Kingston, ON, Canada.
[Day, Troy] Queens Univ, Dept Biol, Kingston, ON K7L 3N6, Canada.
[Read, Andrew F.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Huijben, S (reprint author), CRESIB Barcelona Ctr Int Hlth Res, Barcelona, Spain.
EM silviehuijben@gmail.com; a.read@psu.edu
FU National Institute of General Medical Sciences [R01GM089932]
FX This work was supported by the National Institute of General Medical
Sciences (R01GM089932). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 52
TC 28
Z9 28
U1 1
U2 28
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD SEP
PY 2013
VL 9
IS 9
AR e1003578
DI 10.1371/journal.ppat.1003578
PG 9
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 224WM
UT WOS:000324922300011
PM 24068922
ER
PT J
AU Omsland, A
Hackstadt, T
Heinzen, RA
AF Omsland, Anders
Hackstadt, Ted
Heinzen, Robert A.
TI Bringing Culture to the Uncultured: Coxiella burnetii and Lessons for
Obligate Intracellular Bacterial Pathogens
SO PLOS PATHOGENS
LA English
DT Article
ID CHLAMYDIA-TRACHOMATIS; LEGIONELLA-PNEUMOPHILA; PROTEINS; TRANSPORT;
DIFFERENTIATION; MACROPHAGES; INCLUSION; PROBES; CELLS
C1 [Omsland, Anders; Hackstadt, Ted] NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT USA.
[Heinzen, Robert A.] NIAID, Coxiella Pathogenesis Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT USA.
RP Omsland, A (reprint author), NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT USA.
EM rheinzen@niaid.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Institute of Allergy and Infectious Diseases
FX This work was funded by the Intramural Research Program of the National
Institutes of Health, National Institute of Allergy and Infectious
Diseases. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 31
TC 6
Z9 6
U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD SEP
PY 2013
VL 9
IS 9
AR e1003540
DI 10.1371/journal.ppat.1003540
PG 5
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 224WM
UT WOS:000324922300005
PM 24039571
ER
PT J
AU Hikosaka, O
Yamamoto, S
Yasuda, M
Kim, HF
AF Hikosaka, Okihide
Yamamoto, Shinya
Yasuda, Masaharu
Kim, Hyoung F.
TI Why skill matters
SO TRENDS IN COGNITIVE SCIENCES
LA English
DT Review
ID SACCADIC EYE-MOVEMENTS; BASAL GANGLIA; MOTOR SKILL; SELECTIVE ATTENTION;
VISUAL-ATTENTION; CAUDATE-NUCLEUS; PARIETAL CORTEX; HABIT FORMATION;
RESPONSE BIAS; REWARD
AB Maximizing rewards per unit time is ideal for success and survival in humans and animals. This goal can be approached by speeding up behavior aiming at rewards and this is done most efficiently by acquiring skills. Importantly, reward-directed skills consist of two components: finding a good object (i.e., object skill) and acting on the object (i.e., action skill), which occur sequentially. Recent studies suggest that object skill is based on high-capacity memory for object value associations. When a learned object is encountered the corresponding memory is quickly expressed as a valuebased gaze bias, leading to the automatic acquisition or avoidance of the object. Object skill thus plays a crucial role in increasing rewards per unit time.
C1 [Hikosaka, Okihide; Yamamoto, Shinya; Yasuda, Masaharu; Kim, Hyoung F.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
[Yamamoto, Shinya] Natl Inst Adv Ind Sci & Technol, Human Technol Res Inst, Tsukuba, Ibaraki 3058568, Japan.
RP Hikosaka, O (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM oh@lsr.nei.nih.gov
RI Yamamoto, Shinya/S-3134-2016
OI Yamamoto, Shinya/0000-0002-0505-8848
FU intramural research program at the National Eye Institute
FX This work was supported by the intramural research program at the
National Eye Institute.
NR 108
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U1 7
U2 35
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 1364-6613
J9 TRENDS COGN SCI
JI TRENDS COGN. SCI.
PD SEP
PY 2013
VL 17
IS 9
BP 434
EP 441
DI 10.1016/j.tics.2013.07.001
PG 8
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA 223DJ
UT WOS:000324784000004
PM 23911579
ER
PT J
AU Ferrari, PF
Tramacere, A
Simpson, EA
Iriki, A
AF Ferrari, Pier F.
Tramacere, Antonella
Simpson, Elizabeth A.
Iriki, Atsushi
TI Mirror neurons through the lens of epigenetics
SO TRENDS IN COGNITIVE SCIENCES
LA English
DT Review
ID GENE-EXPRESSION; PREMOTOR CORTEX; FACE PREFERENCE; MATERNAL-CARE;
PARIETAL LOBE; SYSTEM; BRAIN; PLASTICITY; EVOLUTION; MOTOR
AB The consensus view in mirror neuron research is that mirror neurons comprise a uniform, stable execution observation matching system. In this opinion article, we argue that, in light of recent evidence, this is at best an incomplete and oversimplified view of mirror neurons, where activity is actually variable and more plastic than previously theorized. We propose an epigenetic account for understanding developmental changes in sensorimotor systems, including variations in mirror neuron activity. Although associative and genetic accounts fail to consider the complexity of genetic and nongenetic interactions, we propose a new evolutionary developmental biology (evo-devo) perspective, which predicts that environmental differences early in development should produce variations in mirror neuron response patterns, tuning them to the social environment.
C1 [Ferrari, Pier F.; Tramacere, Antonella; Simpson, Elizabeth A.] Univ Parma, Dipartimento Neurosci, I-43100 Parma, Italy.
[Simpson, Elizabeth A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Poolesville, MD USA.
[Tramacere, Antonella; Iriki, Atsushi] RIKEN Brain Sci Inst, Saitama, Japan.
RP Ferrari, PF (reprint author), Univ Parma, Dipartimento Neurosci, I-43100 Parma, Italy.
EM pierfrancesco.ferrari@unipr.it
OI Simpson, Elizabeth/0000-0003-2715-2533
FU Division of Intramural Research, NICHD [P01HD064653]; Worl-dleading
Innovative R&D on Science and Technology
FX This research was supported by the Division of Intramural Research,
NICHD, NICHD P01HD064653, and by the Funding Program for Worl-dleading
Innovative R&D on Science and Technology. We thank Valentina Sclafani
and Sebo Uithol for their comments on an early version of this paper.
NR 76
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U1 4
U2 31
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 1364-6613
J9 TRENDS COGN SCI
JI TRENDS COGN. SCI.
PD SEP
PY 2013
VL 17
IS 9
BP 450
EP 457
DI 10.1016/j.tics.2013.07.003
PG 8
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA 223DJ
UT WOS:000324784000006
PM 23953747
ER
PT J
AU Strober, W
AF Strober, Warren
TI Impact of the gut microbiome on mucosal inflammation
SO TRENDS IN IMMUNOLOGY
LA English
DT Review
DE Gut microbiome; Mucosal regulatory T cells; Anti-inflammatory organisms;
Proinflammatory (colitogenic organisms); Inflammatory Bowel Disease
ID INVASIVE ESCHERICHIA-COLI; CROHNS-DISEASE; BOWEL-DISEASE;
ULCERATIVE-COLITIS; ILEAL MUCOSA; INTESTINAL INFLAMMATION; RECEPTOR;
MICE; COLONIZATION; MACROPHAGES
AB In the past 10 years it has become increasingly apparent that the gut microbiome has profound effects on the immune system to which it is juxtaposed, the mucosal immune system. Here, I explore recent studies in which the effects of the microbiota expand or facilitate anti-inflammatory or regulatory immunological machinery or which favor development of proinflammatory immunological machinery in this system. I then focus on how these opposing processes play out in inflammatory bowel disease (IBD); a disease in which normal immune homeostasis is disturbed and inflammation takes hold.
C1 NIAID, NIH, Bethesda, MD USA.
RP Strober, W (reprint author), NIAID, NIH, Bethesda, MD USA.
EM Wstrober@niaid.nih.gov
FU Intramural NIH HHS [ZIA AI000354-27]
NR 47
TC 20
Z9 21
U1 3
U2 23
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1471-4906
J9 TRENDS IMMUNOL
JI Trends Immunol.
PD SEP
PY 2013
VL 34
IS 9
BP 423
EP 430
DI 10.1016/j.it.2013.07.001
PG 8
WC Immunology
SC Immunology
GA 225OG
UT WOS:000324971600001
PM 23957963
ER
PT J
AU Kadmiel, M
Cidlowski, JA
AF Kadmiel, Mahita
Cidlowski, John A.
TI Glucocorticoid receptor signaling in health and disease
SO TRENDS IN PHARMACOLOGICAL SCIENCES
LA English
DT Review
DE stress hormones; inflammation; nuclear receptor; glucocorticoid-response
element
ID CONGENITAL ADRENAL-HYPERPLASIA; OBSTRUCTIVE PULMONARY-DISEASE; INNATE
IMMUNE-SYSTEM; GENE-EXPRESSION; CARDIOVASCULAR-SYSTEM; RESPONSE
ELEMENTS; FUTURE-DIRECTIONS; LUNG MATURATION; BETA-ISOFORM; NR3C1 GENE
AB Glucocorticoids are steroid hormones regulated in a circadian and stress-associated manner to maintain various metabolic and homeostatic functions that are necessary for life. Synthetic glucocorticoids are widely prescribed drugs for many conditions including asthma, chronic obstructive pulmonary disease (COPD), and inflammatory disorders of the eye. Research in the past few years has begun to unravel the profound complexity of glucocorticoid signaling and has contributed remarkably to improved therapeutic strategies. Glucocorticoids signal through the glucocorticoid receptor (GR), a member of the superfamily of nuclear receptors, in both genomic and non-genomic ways in almost every tissue in the human body. In this review, we provide an update on glucocorticoid receptor signaling and highlight the role of GR signaling in physiological and pathophysiological conditions in the major organ systems in the human body.
C1 [Kadmiel, Mahita; Cidlowski, John A.] NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, 111 TW Alexander Dr,MD F3-07, Res Triangle Pk, NC 27709 USA.
EM cidlows1@niehs.nih.gov
FU NIEHS Intramural Research Program of the National Institutes of Health
FX The authors thank all members of the Molecular Endocrinology Group for
critical reading of this manuscript. They apologize to colleagues whose
work they were unable to cite owing to space limitations. They thank
these individuals for all their work that has significantly contributed
to our current understanding of GR action. This work was supported by
the NIEHS Intramural Research Program of the National Institutes of
Health.
NR 110
TC 109
Z9 112
U1 11
U2 79
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0165-6147
J9 TRENDS PHARMACOL SCI
JI Trends Pharmacol. Sci.
PD SEP
PY 2013
VL 34
IS 9
BP 518
EP 530
DI 10.1016/j.tips.2013.07.003
PG 13
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 229DE
UT WOS:000325241200006
PM 23953592
ER
PT J
AU Restaino, M
Matthews, FE
Minett, T
Albanese, E
Brayne, C
Stephan, BCM
AF Restaino, Marialuisa
Matthews, Fiona E.
Minett, Thais
Albanese, Emiliano
Brayne, Carol
Stephan, Blossom Christa Maree
TI Predicting risk of 2-year incident dementia using the CAMCOG total and
subscale scores
SO AGE AND AGEING
LA English
DT Article
DE cognition; dementia risk prediction; Cambridge Cognitive Examination
(CAMCOG); classification and regression tree (CART) analysis; predictive
accuracy; older people
ID MILD COGNITIVE IMPAIRMENT; CONCISE NEUROPSYCHOLOGICAL TEST; ELDERLY
POPULATION-SAMPLE; PSYCHOMETRIC PROPERTIES; DIAGNOSIS; INSTRUMENT;
PROFILE
AB Objective: to identify cognitive changes associated with an increased risk of 2-year incident dementia using the Cambridge Cognitive Examination (CAMCOG).
Design: longitudinal population representative sample aged 65+ years.
Methods: individuals were from the Medical Research Council Cognitive Function and Ageing Study. Classification and Regression Tree analysis was used to detect the optimal cut-off value for the CAMCOG total, subscales and composite memory and non-memory scores, for predicting dementia. Sensitivity and specificity of each cut-off score were assessed.
Results: from the 2,053 individuals without dementia at the first assessment, 137 developed dementia at the 2-year follow-up. The results indicate similar discriminative accuracy for incident dementia based on the CAMCOG total, memory subscale and composite scores. However, sensitivity and specificity of cut-off values were generally moderate. Scores on the non-memory subscales generally had high sensitivity but low specificity. Compared with the CAMCOG total score they had significantly lower discriminative accuracy.
Conclusion: in a population setting, cut-off scores from the CAMCOG memory subscales predicted dementia with reasonable accuracy. Scores on the non-memory scales have lower accuracy and are not recommend for predicting high-risk cases unless all non-memory subdomain scores are combined. The added value of cognition when assessed using the CAMCOG to other risk factors (e.g. health and genetics) should be tested within a risk prediction framework.
C1 [Restaino, Marialuisa] Univ Salerno, Dept Econ & Stat, Fisciano, SA, Italy.
[Matthews, Fiona E.] Inst Publ Hlth, MRC Biostat Unit, Cambridge CB2 0SR, England.
[Minett, Thais; Brayne, Carol] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB2 0SR, England.
[Albanese, Emiliano] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, WA USA.
[Stephan, Blossom Christa Maree] Newcastle Univ, Inst Hlth & Soc, Newcastle Upon Tyne NE2 4AX, Tyne & Wear, England.
RP Stephan, BCM (reprint author), Newcastle Univ, Inst Hlth & Soc, Baddiley Clark Bldg,Richardson Rd, Newcastle Upon Tyne NE2 4AX, Tyne & Wear, England.
EM blossom.stephan@ncl.ac.uk
RI Restaino, Marialuisa/L-5665-2015;
OI Restaino, Marialuisa/0000-0002-1150-8278; Stephan,
Blossom/0000-0002-1235-360X; Matthews, Fiona/0000-0002-1728-2388
FU Medical Research Council [G9901400]; Department of Health; National
Institute on Aging, National Institutes of Health
FX MRC CFAS has been funded by the Medical Research Council (G9901400) and
Department of Health. E. A. is supported by the Intramural Research
Program of the National Institute on Aging, National Institutes of
Health.
NR 19
TC 4
Z9 5
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0002-0729
J9 AGE AGEING
JI Age Ageing
PD SEP
PY 2013
VL 42
IS 5
BP 649
EP 653
DI 10.1093/ageing/aft082
PG 5
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 204BX
UT WOS:000323341000020
PM 23872637
ER
PT J
AU Kimmel, SE
French, B
Anderson, JL
Gage, BF
Johnson, JA
Rosenberg, YD
Geller, NL
Kasner, SE
Eby, CS
Joo, J
Caldwell, MD
Goldhaber, SZ
Hart, RG
Cifelli, D
Madigan, R
Brensinger, CM
Goldberg, S
Califf, RM
Ellenberg, JH
AF Kimmel, Stephen E.
French, Benjamin
Anderson, Jeffrey L.
Gage, Brian F.
Johnson, Julie A.
Rosenberg, Yves D.
Geller, Nancy L.
Kasner, Scott E.
Eby, Charles S.
Joo, Jungnam
Caldwell, Michael D.
Goldhaber, Samuel Z.
Hart, Robert G.
Cifelli, Denise
Madigan, Rosemary
Brensinger, Colleen M.
Goldberg, Suzanne
Califf, Robert M.
Ellenberg, Jonas H.
CA COAG Investigators
TI Rationale and design of the Clarification of Optimal Anticoagulation
through Genetics trial
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID ORAL ANTICOAGULATION; ATRIAL-FIBRILLATION; AFRICAN-AMERICANS; COAG
TRIAL; WARFARIN; INTENSITY; METAANALYSIS; POPULATION; ALGORITHMS;
CAUCASIANS
AB Background Current dosing practices for warfarin are empiric and result in the need for frequent dose changes as the international normalized ratio gets too high or too low. As a result, patients are put at increased risk for thromboembolism, bleeding, and premature discontinuation of anticoagulation therapy. Prior research has identified clinical and genetic factors that can alter warfarin dose requirements, but few randomized clinical trials have examined the utility of using clinical and genetic information to improve anticoagulation control or clinical outcomes among a large, diverse group of patients initiating warfarin.
Methods The COAG trial is a multicenter, double-blind, randomized trial comparing 2 approaches to guiding warfarin therapy initiation: initiation of warfarin therapy based on algorithms using clinical information plus an individual's genotype using genes known to influence warfarin response ("genotype-guided dosing") versus only clinical information ("clinical-guided dosing") (www.clinicaltrials.gov Identifier: NCT00839657).
Results The COAG trial design is described. The study hypothesis is that, among 1,022 enrolled patients, genotype-guided dosing relative to clinical-guided dosing during the initial dosing period will increase the percentage of time that patients spend in the therapeutic international normalized ratio range in the first 4 weeks of therapy.
Conclusion The COAG will determine if genetic information provides added benefit above and beyond clinical information alone.
C1 [Kimmel, Stephen E.; French, Benjamin; Kasner, Scott E.; Cifelli, Denise; Madigan, Rosemary; Brensinger, Colleen M.; Ellenberg, Jonas H.] Univ Penn Hlth Syst, Perelman Sch Med, Philadelphia, PA USA.
[Anderson, Jeffrey L.] Univ Utah, Sch Med, Salt Lake City, UT USA.
[Gage, Brian F.; Eby, Charles S.] Washington Univ, Sch Med, St Louis, MO USA.
[Johnson, Julie A.] Univ Florida, Gainesville, FL USA.
[Rosenberg, Yves D.; Geller, Nancy L.; Joo, Jungnam; Goldberg, Suzanne] NHLBI, NIH, Bethesda, MD 20892 USA.
[Caldwell, Michael D.] Marshfield Clin Fdn Med Res & Educ, Marshfield, WI USA.
[Goldhaber, Samuel Z.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Hart, Robert G.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Ellenberg, Jonas H.] Duke Univ, Med Ctr, Durham, NC USA.
RP Kimmel, SE (reprint author), Univ Penn, Sch Med, 923 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA.
EM stevek@mail.med.upenn.edu
FU National Heart Lung and Blood Institute [HHSN268200800003C]
FX This work was supported under contract HHSN268200800003C from the
National Heart Lung and Blood Institute.
NR 32
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U1 0
U2 5
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
J9 AM HEART J
JI Am. Heart J.
PD SEP
PY 2013
VL 166
IS 3
BP 435
EP +
DI 10.1016/j.ahj.2013.04.009
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 214UZ
UT WOS:000324163600016
PM 24016491
ER
PT J
AU Mentz, RJ
Bittner, V
Schulte, PJ
Fleg, JL
Pina, IL
Keteyian, SJ
Moe, G
Nigam, A
Swank, AM
Onwuanyi, AE
Fitz-Gerald, M
Kao, A
Ellis, SJ
Kraus, WE
Whellan, DJ
O'Connor, CM
AF Mentz, Robert J.
Bittner, Vera
Schulte, Phillip J.
Fleg, Jerome L.
Pina, Ileana L.
Keteyian, Steven J.
Moe, Gordon
Nigam, Anil
Swank, Ann M.
Onwuanyi, Anekwe E.
Fitz-Gerald, Meredith
Kao, Andrew
Ellis, Stephen J.
Kraus, William E.
Whellan, David J.
O'Connor, Christopher M.
TI Race, exercise training, and outcomes in chronic heart failure: Findings
from Heart Failure - A Controlled Trial Investigating Outcomes in
Exercise TraiNing (HF-ACTION)
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID QUALITY-OF-CARE; RANDOMIZED CONTROLLED-TRIAL; RACIAL-DIFFERENCES;
AFRICAN-AMERICANS; MEDICARE BENEFICIARIES; STABLE OUTPATIENTS;
PROGNOSTIC VALUE; RISK-FACTORS; MORTALITY; SCORE
AB Background The strength of race as an independent predictor of long-term outcomes in a contemporary chronic heart failure (HF) population and its association with exercise training response have not been well established. We aimed to investigate the association between race and outcomes and to explore interactions with exercise training in patients with ambulatory HF.
Methods We performed an analysis of HF-ACTION, which randomized 2331 patients with HF having an ejection fraction <= 35% to usual care with or without exercise training. We examined characteristics and outcomes (mortality/hospitalization, mortality, and cardiovascular mortality/HF hospitalization) by race using adjusted Cox models and explored an interaction with exercise training.
Results There were 749 self-identified black patients (33%). Blacks were younger with significantly more hypertension and diabetes, less ischemic etiology, and lower socioeconomic status versus whites. Blacks had shorter 6-minute walk distance and lower peak VO2 at baseline. Over a median follow-up of 2.5 years, black race was associated with increased risk for all outcomes except mortality. After multivariable adjustment, black race was associated with increased mortality/hospitalization (hazard ratio [HR] 1.16, 95% CI 1.01-1.33) and cardiovascular mortality/HF hospitalization (HR 1.46, 95% CI 1.20-1.77). The hazard associated with black race was largely caused by increased HF hospitalization (HR 1.58, 95% CI 1.27-1.96), given similar cardiovascular mortality. There was no interaction between race and exercise training on outcomes (P > .5).
Conclusions Black race in patients with chronic HF was associated with increased prevalence of modifiable risk factors, lower exercise performance, and increased HF hospitalization, but not increased mortality or a differential response to exercise training.
C1 [Mentz, Robert J.; Kraus, William E.; O'Connor, Christopher M.] Duke Univ, Durham, NC USA.
[Bittner, Vera; Fitz-Gerald, Meredith] Univ Alabama Birmingham, Birmingham, AL USA.
[Schulte, Phillip J.; Ellis, Stephen J.] DCRI, Durham, NC USA.
[Fleg, Jerome L.] NHLBI, Bethesda, MD 20892 USA.
[Pina, Ileana L.] Montefiore Einstein Med Ctr, New York, NY USA.
[Keteyian, Steven J.] Henry Ford Hosp, Detroit, MI 48202 USA.
[Moe, Gordon] St Michaels Hosp, Toronto, ON M5B 1W8, Canada.
[Nigam, Anil] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.
[Nigam, Anil] Univ Montreal, Montreal, PQ, Canada.
[Swank, Ann M.] Univ Louisville, Louisville, KY 40292 USA.
[Onwuanyi, Anekwe E.] Morehouse Sch Med, Atlanta, GA 30310 USA.
[Kao, Andrew] St Lukes Midamer Heart Inst, Kansas City, MO USA.
[Whellan, David J.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
RP Mentz, RJ (reprint author), 2301 Erwin Rd, Durham, NC 27710 USA.
EM robert.mentz@duke.edu
OI Bittner, Vera/0000-0001-9456-850X; Kraus, William E/0000-0003-1930-9684
FU National Heart, Lung, and Blood Institute
FX The HF-ACTION study was funded by the National Heart, Lung, and Blood
Institute, but no extramural funding was used to support the current
analysis. The authors are solely responsible for the design and conduct
of this study, all analyses, the drafting and editing of the manuscript,
and its final contents.
NR 31
TC 13
Z9 13
U1 1
U2 10
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
J9 AM HEART J
JI Am. Heart J.
PD SEP
PY 2013
VL 166
IS 3
BP 488
EP +
DI 10.1016/j.ahj.2013.06.002
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 214UZ
UT WOS:000324163600023
PM 24016498
ER
PT J
AU Allison, MA
Bluemke, DA
McClelland, R
Cushman, M
Criqui, MH
Polak, JF
Lima, JA
AF Allison, Matthew A.
Bluemke, David A.
McClelland, Robyn
Cushman, Mary
Criqui, Michael H.
Polak, Joseph F.
Lima, Joao A.
TI Relation of Leptin to Left Ventricular Hypertrophy (from the
Multi-Ethnic Study of Atherosclerosis)
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID CARDIAC-HYPERTROPHY; MAGNETIC-RESONANCE; WEIGHT-LOSS; OBESITY; MICE;
MASS; HEART; ASSOCIATION; RESISTANCE; IMPACT
AB Increasing adiposity increases the risk for left ventricular (LV) hypertrophy. Adipokines are hormone-like substances from adipose tissue that influence several metabolic pathways relevant to LV hypertrophy. Data were obtained from participants enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA) who underwent magnetic resonance imaging of the heart and who also had fasting venous blood assayed for 4 distinct adipokines (adiponectin, leptin, tumor necrosis factor-alpha, and resistin). One-thousand four hundred sixty four MESA participants had complete data. The mean age was 61.5 years, the mean body mass index was 27.6 kg/m(2), and 49% were women. With adjustment for age, gender, race, height, and weight, multivariate linear regression modeling revealed that a 1-SD increment in leptin was significantly associated with smaller LV mass (beta: -4.66% predicted, p <0.01), LV volume (-5.87% predicted, p <0.01), stroke volume (-3.23 ml, p <0.01), and cardiac output (-120 ml/min, p = 0.01) as well as a lower odds ratio for the presence of LV hypertrophy (odds ratio 0.65, p <0.01), but a higher ejection fraction (0.44%, p = 0.05). Additional adjustment for the traditional cardiovascular disease risk factors, insulin resistance, physical activity, education, income, inflammatory biomarkers, other selected adipokines, and pericardial fat did not materially change the magnitude or significance of the associations. The associations between the other adipokines and LV structure and function were inconsistent and largely nonsignificant. In conclusion, the results indicate that higher levels of leptin are associated with more favorable values of several measures of LV structure and function. Published by Elsevier Inc.
C1 [Allison, Matthew A.; Criqui, Michael H.] Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA.
[Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, NIH, Ctr Clin, Bethesda, MD USA.
[McClelland, Robyn] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Cushman, Mary] Univ Vermont, Dept Med, Burlington, VT USA.
[Polak, Joseph F.] Tufts Med Ctr, Dept Radiol, Boston, MA USA.
[Lima, Joao A.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
RP Allison, MA (reprint author), Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA.
EM mallison@ucsd.edu
OI Bluemke, David/0000-0002-8323-8086; Allison, Matthew/0000-0003-0777-8272
FU National Heart, Lung, and Blood Institute, Bethesda, Maryland
[R01-HL-088451, HC-95159, N01-HC-95165, N01-HC-95169]
FX This research was supported by a grant R01-HL-088451 and contracts
N01-HC-95159 through N01-HC-95165 and N01-HC-95169 from the National
Heart, Lung, and Blood Institute, Bethesda, Maryland.
NR 26
TC 15
Z9 15
U1 0
U2 4
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 SEP 1
PY 2013
VL 112
IS 5
BP 726
EP 730
DI 10.1016/j.amjcard.2013.04.053
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 210ZZ
UT WOS:000323875200019
PM 23711806
ER
PT J
AU Wyss, A
Hashibe, M
Chuang, SC
Lee, YCA
Zhang, ZF
Yu, GP
Winn, DM
Wei, QY
Talamini, R
Szeszenia-Dabrowska, N
Sturgis, EM
Smith, E
Shangina, O
Schwartz, SM
Schantz, S
Rudnai, P
Purdue, MP
Eluf-Neto, J
Muscat, J
Morgenstern, H
Michaluart, P
Menezes, A
Matos, E
Mates, IN
Lissowska, J
Levi, F
Lazarus, P
La Vecchia, C
Koifman, S
Herrero, R
Hayes, RB
Franceschi, S
Wunsch, V
Fernandez, L
Fabianova, E
Daudt, AW
Dal Maso, L
Curado, MP
Chen, C
Castellsague, X
de Carvalho, MB
Cadoni, G
Boccia, S
Brennan, P
Boffetta, P
Olshan, AF
AF Wyss, Annah
Hashibe, Mia
Chuang, Shu-Chun
Lee, Yuan-Chin Amy
Zhang, Zuo-Feng
Yu, Guo-Pei
Winn, Deborah M.
Wei, Qingyi
Talamini, Renato
Szeszenia-Dabrowska, Neonila
Sturgis, Erich M.
Smith, Elaine
Shangina, Oxana
Schwartz, Stephen M.
Schantz, Stimson
Rudnai, Peter
Purdue, Mark P.
Eluf-Neto, Jose
Muscat, Joshua
Morgenstern, Hal
Michaluart, Pedro, Jr.
Menezes, Ana
Matos, Elena
Mates, Ioan Nicolae
Lissowska, Jolanta
Levi, Fabio
Lazarus, Philip
La Vecchia, Carlo
Koifman, Sergio
Herrero, Rolando
Hayes, Richard B.
Franceschi, Silvia
Wuensch-Filho, Victor
Fernandez, Leticia
Fabianova, Eleonora
Daudt, Alexander W.
Dal Maso, Luigino
Curado, Maria Paula
Chen, Chu
Castellsague, Xavier
de Carvalho, Marcos Brasilino
Cadoni, Gabriella
Boccia, Stefania
Brennan, Paul
Boffetta, Paolo
Olshan, Andrew F.
TI Cigarette, Cigar, and Pipe Smoking and the Risk of Head and Neck
Cancers: Pooled Analysis in the International Head and Neck Cancer
Epidemiology Consortium
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Review
DE head and neck neoplasms; smoking
ID UPPER AERODIGESTIVE TRACT; UNITED-STATES VETERANS; UPPER
DIGESTIVE-TRACT; ORAL-CAVITY; ALCOHOL-CONSUMPTION; PHARYNGEAL CANCER;
TOBACCO SMOKING; DRINKING; MEN; ASSOCIATION
AB Cigar and pipe smoking are considered risk factors for head and neck cancers, but the magnitude of effect estimates for these products has been imprecisely estimated. By using pooled data from the International Head and Neck Cancer Epidemiology (INHANCE) Consortium (comprising 13,935 cases and 18,691 controls in 19 studies from 1981 to 2007), we applied hierarchical logistic regression to more precisely estimate odds ratios and 95% confidence intervals for cigarette, cigar, and pipe smoking separately, compared with reference groups of those who had never smoked each single product. Odds ratios for cigar and pipe smoking were stratified by ever cigarette smoking. We also considered effect estimates of smoking a single product exclusively versus never having smoked any product (reference group). Among never cigarette smokers, the odds ratio for ever cigar smoking was 2.54 (95% confidence interval (CI): 1.93, 3.34), and the odds ratio for ever pipe smoking was 2.08 (95% CI: 1.55, 2.81). These odds ratios increased with increasing frequency and duration of smoking (P-trend <= 0.0001). Odds ratios for cigar and pipe smoking were not elevated among ever cigarette smokers. Head and neck cancer risk was elevated for those who reported exclusive cigar smoking (odds ratio = 3.49, 95% CI: 2.58, 4.73) or exclusive pipe smoking (odds ratio = 3.71, 95% CI: 2.59, 5.33). These results suggest that cigar and pipe smoking are independently associated with increased risk of head and neck cancers.
C1 [Wyss, Annah; Olshan, Andrew F.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
[Hashibe, Mia; Lee, Yuan-Chin Amy] Univ Utah, Sch Med, Dept Family & Prevent Med, Salt Lake City, UT 84112 USA.
[Chuang, Shu-Chun] Natl Hlth Res Inst, Inst Populat Hlth Sci, Miaoli, Taiwan.
[Zhang, Zuo-Feng] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA.
[Yu, Guo-Pei] New York Med Coll, Dept Otolaryngol, New York, NY USA.
[Yu, Guo-Pei] Peking Univ, Med Informat Ctr, Beijing 100871, Peoples R China.
[Winn, Deborah M.] NIH, NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Wei, Qingyi; Sturgis, Erich M.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Div Canc Prevent & Populat Sci, Houston, TX 77030 USA.
[Talamini, Renato; Dal Maso, Luigino] Natl Canc Inst Aviano, Epidemiol & Biostat Unit, Aviano, Italy.
[Szeszenia-Dabrowska, Neonila] Inst Occupat Med, Dept Epidemiol, Lodz, Poland.
[Sturgis, Erich M.] Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, Div Surg, Houston, TX 77030 USA.
[Smith, Elaine] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA.
[Shangina, Oxana] NN Blokhin Canc Res Ctr, Inst Carcinogenesis, Dept Epidemiol & Prevent, Moscow, Russia.
[Schwartz, Stephen M.; Chen, Chu] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
[Schwartz, Stephen M.; Chen, Chu] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Schantz, Stimson] New York Eye & Ear Infirm, Dept Otolaryngol, Biostat & Epidemiol Serv, New York, NY 10003 USA.
[Rudnai, Peter] Natl Inst Environm Hlth, Dept Environm Epidemiol, Budapest, Hungary.
[Purdue, Mark P.] NIH, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NCI, Bethesda, MD 20892 USA.
[Eluf-Neto, Jose] Univ Sao Paulo, Fac Med, Dept Prevent Med, Sao Paulo, Brazil.
[Muscat, Joshua] Penn State Coll Med, Dept Publ Hlth Sci, Hershey, PA USA.
[Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA.
[Morgenstern, Hal] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Michaluart, Pedro, Jr.] Univ Sao Paulo, Fac Med, Head & Neck Serv, Sao Paulo, Brazil.
[Menezes, Ana] Univ Fed Pelotas, Pelotas, Brazil.
[Matos, Elena] Univ Buenos Aires, Angel H Roffo Inst Oncol, Buenos Aires, DF, Argentina.
[Mates, Ioan Nicolae] Carol Davila Univ Med & Pharm, Bucharest, Romania.
[Lissowska, Jolanta] Maria Sklodowska Curie Mem Canc Ctr & Inst Oncol, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Levi, Fabio] Vaudois Univ, Ctr Hosp, Canc Epidemiol Unit, Lausanne, Switzerland.
[Levi, Fabio] Vaudois Univ, Ctr Hosp, Vaud Canc Registry, Lausanne, Switzerland.
[Levi, Fabio] Univ Lausanne, Lausanne, Switzerland.
[Lazarus, Philip] Washington State Univ, Coll Pharm, Dept Pharmaceut Sci, Spokane, WA USA.
[La Vecchia, Carlo] Univ Milan, Mario Negri Inst Pharmacol Res, Dept Epidemiol, Milan, Italy.
[La Vecchia, Carlo] Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy.
[Koifman, Sergio] Fundacao Oswaldo Cruz, Natl Sch Publ Hlth, Dept Epidemiol, Rio De Janeiro, Brazil.
[Herrero, Rolando] Int Agcy Res Canc, Prevent & Implementat Grp, F-69372 Lyon, France.
[Hayes, Richard B.] NYU, Sch Med, Div Epidemiol, Dept Populat Hlth, New York, NY USA.
[Franceschi, Silvia] Int Agcy Res Canc, Infect & Canc Epidemiol Grp, F-69372 Lyon, France.
[Wuensch-Filho, Victor] Univ Sao Paulo, Fac Publ Hlth, Dept Epidemiol, Sao Paulo, Brazil.
[Fernandez, Leticia] Inst Oncol & Radiobiol, Havana, Cuba.
[Fabianova, Eleonora] Reg Author Publ Hlth Banska Bystrica, Banska Bystrica, Slovakia.
[Daudt, Alexander W.] Clin Hosp Porto Alegre, Porto Alegre, RS, Brazil.
[Curado, Maria Paula; Boffetta, Paolo] Int Prevent Res Inst, Lyon, France.
[Castellsague, Xavier] Catalan Inst Oncol, Lhospitalet De Llobregat, Spain.
[de Carvalho, Marcos Brasilino] Heliopolis Hosp, Mol Biol Lab, Sao Paulo, Brazil.
[Cadoni, Gabriella] Univ Cattolica Sacro Cuore, A Gemelli Hosp, Dept Head & Neck Surg Otorhinolaryngol, I-00168 Rome, Italy.
[Boccia, Stefania] Univ Cattolica Sacro Cuore, Inst Hyg, I-00168 Rome, Italy.
[Boccia, Stefania] Inst Res Hospitalizat & Hlth Care, Rome, Italy.
[Brennan, Paul] Int Agcy Res Canc, Genet Epidemiol Grp, F-69372 Lyon, France.
[Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA.
RP Olshan, AF (reprint author), Gillings Sch Global Publ Hlth, Dept Epidemiol, CB 7435,2101B McGavran Greenberg Hall, Chapel Hill, NC 27599 USA.
EM andy_olshan@unc.edu
RI Chuang, Shu-Chun/N-3358-2013; Menezes, Ana/G-7266-2012; Castellsague
Pique, Xavier/N-5795-2014; Szeszenia-Dabrowska, Neonila/F-7190-2010;
Eluf-Neto, Jose/B-2522-2009; Purdue, Mark/C-9228-2016; Curado, Maria
Paula/M-6200-2013; Mates, Ioan Nicolae/E-9255-2017
OI Lissowska, Jolanta/0000-0003-2695-5799; dal maso,
luigino/0000-0001-6163-200X; La Vecchia, Carlo/0000-0003-1441-897X;
Hayes, Richard/0000-0002-0918-661X; Ioan Nicoale,
Mates/0000-0001-7210-0615; Schwartz, Stephen/0000-0001-7499-8502;
Castellsague Pique, Xavier/0000-0002-0802-3595; Eluf-Neto,
Jose/0000-0001-7504-2115; Purdue, Mark/0000-0003-1177-3108; Curado,
Maria Paula/0000-0001-8172-2483;
FU Union for International Cancer Control International Cancer Technology
Transfer Fellowship; National Cancer Institute [T32-CA09330, R03
CA113157]; National Institute of Environmental Health Sciences
[T32ES007018]
FX This work was supported by a Union for International Cancer Control
International Cancer Technology Transfer Fellowship, by the National
Cancer Institute (grants T32-CA09330 and R03 CA113157), and by the
National Institute of Environmental Health Sciences (grant T32ES007018).
NR 34
TC 27
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U1 1
U2 36
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 SEP 1
PY 2013
VL 178
IS 5
BP 679
EP 690
DI 10.1093/aje/kwt029
PG 12
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 211YX
UT WOS:000323949800003
PM 23817919
ER
PT J
AU Olson, SH
Hsu, M
Satagopan, JM
Maisonneuve, P
Silverman, DT
Lucenteforte, E
Anderson, KE
Borgida, A
Bracci, PM
Bueno-de-Mesquita, HB
Cotterchio, M
Dai, Q
Duell, EJ
Fontham, EH
Gallinger, S
Holly, EA
Ji, BT
Kurtz, RC
La Vecchia, C
Lowenfels, AB
Luckett, B
Ludwig, E
Petersen, GM
Polesel, J
Seminara, D
Strayer, L
Talamini, R
AF Olson, Sara H.
Hsu, Meier
Satagopan, Jaya M.
Maisonneuve, Patrick
Silverman, Debra T.
Lucenteforte, Ersilia
Anderson, Kristin E.
Borgida, Ayelet
Bracci, Paige M.
Bueno-de-Mesquita, H. Bas
Cotterchio, Michelle
Dai, Qi
Duell, Eric J.
Fontham, Elizabeth H.
Gallinger, Steven
Holly, Elizabeth A.
Ji, Bu-Tian
Kurtz, Robert C.
La Vecchia, Carlo
Lowenfels, Albert B.
Luckett, Brian
Ludwig, Emmy
Petersen, Gloria M.
Polesel, Jerry
Seminara, Daniela
Strayer, Lori
Talamini, Renato
CA Pancreatic Canc Case-Control Conso
TI Allergies and Risk of Pancreatic Cancer: A Pooled Analysis From the
Pancreatic Cancer Case-Control Consortium
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Review
DE allergic rhinitis; case-control studies; hypersensitivity; pancreatic
neoplasms
ID NUTRITION EXAMINATION SURVEY; MEDICAL CONDITIONS; NATIONAL-HEALTH;
LIFE-STYLE; HISTORY; POPULATION; ATOPY; ASTHMA; GLIOMA; ANTIHISTAMINE
AB In order to quantify the risk of pancreatic cancer associated with history of any allergy and specific allergies, to investigate differences in the association with risk according to age, gender, smoking status, or body mass index, and to study the influence of age at onset, we pooled data from 10 case-control studies. In total, there were 3,567 cases and 9,145 controls. Study-specific odds ratios and 95% confidence intervals were calculated by using unconditional logistic regression adjusted for age, gender, smoking status, and body mass index. Between-study heterogeneity was assessed by using the Cochran Q statistic. Study-specific odds ratios were pooled by using a random-effects model. The odds ratio for any allergy was 0.79 (95% confidence interval (CI): 0.62, 1.00) with heterogeneity among studies (P < 0.001). Heterogeneity was attributable to one study; with that study excluded, the pooled odds ratio was 0.73 (95% CI: 0.64, 0.84) (P-heterogeneity = 0.23). Hay fever (odds ratio = 0.74, 95% CI: 0.56, 0.96) and allergy to animals (odds ratio = 0.62, 95% CI: 0.41, 0.94) were related to lower risk, while there was no statistically significant association with other allergies or asthma. There were no major differences among subgroups defined by age, gender, smoking status, or body mass index. Older age at onset of allergies was slightly more protective than earlier age.
C1 [Olson, Sara H.; Hsu, Meier; Satagopan, Jaya M.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
[Maisonneuve, Patrick] European Inst Oncol, Div Epidemiol & Biostat, Milan, Italy.
[Silverman, Debra T.; Ji, Bu-Tian] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Lucenteforte, Ersilia; La Vecchia, Carlo] Mario Negri Inst Pharmacol Res, Dept Epidemiol, Milan, Italy.
[Lucenteforte, Ersilia] Univ Florence, Dept Preclin & Clin Pharmacol, Florence, Italy.
[Polesel, Jerry; Talamini, Renato] Ctr Riferimento Oncol, I-33081 Aviano, PN, Italy.
[Bracci, Paige M.; Fontham, Elizabeth H.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Fontham, Elizabeth H.] Louisiana State Univ, Hlth Sci Ctr, Dept Publ Hlth & Prevent Med, New Orleans, LA USA.
[Luckett, Brian] Tulane Univ, Sch Publ Hlth & Trop Med, Prevent Res Ctr, New Orleans, LA USA.
[Cotterchio, Michelle] Canc Care Ontario, Prevent & Canc Control, Toronto, ON, Canada.
[Borgida, Ayelet] Mt Sinai Hosp, Zane Cohen Ctr Digest Dis, Toronto, ON M5G 1X5, Canada.
[Dai, Qi] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Dept Med, Nashville, TN 37212 USA.
[Duell, Eric J.] Catalan Inst Oncol, Unit Nutr Environm & Canc, Barcelona, Spain.
[Anderson, Kristin E.; Strayer, Lori] Univ Minnesota, Div Epidemiol & Community Hlth, Masonic Canc Ctr, Minneapolis, MN USA.
[Seminara, Daniela] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands.
[Bueno-de-Mesquita, H. Bas] Univ Med Ctr, Dept Gastroenterol & Hepatol, Utrecht, Netherlands.
[Gallinger, Steven] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Ctr Canc Genet, Toronto, ON M5G 1X5, Canada.
[Kurtz, Robert C.; Ludwig, Emmy] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
[Lowenfels, Albert B.] New York Med Coll, Dept Surg, Valhalla, NY 10595 USA.
[Petersen, Gloria M.] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA.
[Petersen, Gloria M.] Mayo Clin, Coll Med, Dept Gastroenterol, Rochester, MN USA.
[Petersen, Gloria M.] Mayo Clin, Coll Med, Dept Med Genet, Rochester, MN USA.
RP Olson, SH (reprint author), Dept Epidemiol & Biostat, 307 East 63rd St,3rd Floor, New York, NY 10065 USA.
EM olsons@mskcc.org
RI Gallinger, Steven/E-4575-2013;
OI La Vecchia, Carlo/0000-0003-1441-897X; Lucenteforte,
Ersilia/0000-0001-5608-5902; Maisonneuve, Patrick/0000-0002-5309-4704;
Duell, Eric J/0000-0001-5256-0163; Satagopan, Jaya/0000-0001-7102-5633;
Polesel, Jerry/0000-0001-9381-1520
FU National Cancer Institute, National Institutes of Health [CA141570,
CA137420, CA58697, CA97075, CA74783, CA098889, CA59706, CA108370,
CA109767, CA89726, CA121846]; Italian Association for Cancer Research
(AIRC) [10068]; Ministry of Welfare, Health, and Culture [808]; Polish
Cancer Program [PR-6]; Cancer Research Society; Fondation Hotel-Dieu de
Montreal; Fonds de la Recherche en Sante du Quebec-Sante; National
Cancer Institute of Canada; Louisiana Board of Regents Millennium Trust
Health Excellence Fund [HEF (20002005]; Intramural Research Program of
the Division of Cancer Epidemiology and Genetics, National Cancer
Institute, National Institutes of Health [N01-CP-51090, N01-CP-51089,
N01-CP-51092, N01-CP-05225, N01-CP31022, N01-CP-05227]; Rombauer
Pancreatic Cancer Research Fund; California Department of Public Health;
National Cancer Institute's Surveillance, Epidemiology, and End Results
Program [N01-PC-35136]; Centers for Disease Control and Prevention's
National Program of Cancer Registries [U55/CCR921930-02]; Prevention,
Control, and Population Research Goldstein Award; Society of the MSKCC;
Geoffrey Beene Cancer Research Fund; Christopher D. Smithers Foundation,
Inc.; Spanish Ministry of Health [ISCIII RETICC RD06/0020]
FX This pooled analysis was supported by grants CA141570 (to S. H. O.) and
CA137420 (to J. M. S.) from the National Cancer Institute, National
Institutes of Health. The Milan and Italy studies were supported by the
Italian Association for Cancer Research (AIRC, Project 10068). The
Minnesota study was supported by grant CA58697 from the National Cancer
Institute, National Institutes of Health. The SEARCH study in Utrecht,
the Netherlands, was supported by grant 808 from the Ministry of
Welfare, Health, and Culture (formerly Ministry of Health and
Environmental Hygiene) of the Netherlands. The SEARCH study in Opole,
Poland, was funded by Polish Cancer Program PR-6. The SEARCH study in
Montreal, Canada, was supported by the Cancer Research Society, the
Fondation Hotel-Dieu de Montreal, and the Fonds de la Recherche en Sante
du Quebec-Sante. The SEARCH study in Toronto was supported by the
National Cancer Institute of Canada. The Louisiana State University
study was supported by the Louisiana Board of Regents Millennium Trust
Health Excellence Fund (Project 5: HEF (20002005, Genetics Studies in
the Acadian Population)). The Ontario Pancreas Cancer Study was
supported by grants CA97075 (as part of the Pancreatic Cancer Genetic
Epidemiology (PACGENE) Consortium) and CA74783 from the National Cancer
Institute, National Institutes of Health; the Lustgarten Foundation for
Pancreatic Cancer Research; and PancreaticCancerCanada.
TheNationalCancerInstitute study was funded by the Intramural Research
Program of the Division of Cancer Epidemiology and Genetics, National
Cancer Institute, National Institutes of Health (N01-CP-51090,
N01-CP-51089, N01-CP-51092, N01-CP-05225, N01-CP31022, N01-CP-05227).
The University of California, San Francisco, study was supported in part
by grants CA098889, CA59706, CA108370, CA109767, CA89726, andCA121846
from the National Cancer Institute, National Institutes of Health, and
by the Rombauer Pancreatic Cancer Research Fund. The collection of
cancer incidence data for the University of California, San Francisco,
study was supported by the California Department of Public Health as
part of the statewide cancer reporting program; the National Cancer
Institute's Surveillance, Epidemiology, and End Results Program under
contract N01-PC-35136 awarded to the Northern California Cancer Center;
and the Centers for Disease Control and Prevention's National Program of
Cancer Registries, under agreement U55/CCR921930-02 awarded to the
Public Health Institute. The Pancreatic Cancer Family Registry at the
MSKCC was supported by the Prevention, Control, and Population Research
Goldstein Award, the Society of the MSKCC, and the Geoffrey Beene Cancer
Research Fund. Financial support for A. B. L. is from the Christopher D.
Smithers Foundation, Inc. E. J. D. is supported by the Spanish Ministry
of Health (ISCIII RETICC RD06/0020).
NR 38
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Z9 15
U1 0
U2 20
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD SEP 1
PY 2013
VL 178
IS 5
BP 691
EP 700
DI 10.1093/aje/kwt052
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 211YX
UT WOS:000323949800004
PM 23820785
ER
PT J
AU Mannisto, T
Mendola, P
Reddy, U
Laughon, SK
AF Maennistoe, Tuija
Mendola, Pauline
Reddy, Uma
Laughon, S. Katherine
TI Neonatal Outcomes and Birth Weight in Pregnancies Complicated by
Maternal Thyroid Disease
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE anemia; neonatal; birth weight; intensive care; neonatal; pregnancy;
respiratory distress syndrome; newborn; thyroid diseases
ID POPULATION-BASED COHORT; SUBCLINICAL HYPOTHYROIDISM; GESTATIONAL-AGE;
DYSFUNCTION; FETAL; HYPOTHYROXINEMIA; HYPERTHYROIDISM; EPIDEMIOLOGY;
POSTPARTUM; CONCEPTION
AB Maternal hypothyroidism has previously been shown to increase risk for neonatal intensive care treatment, but otherwise the association between thyroid diseases and neonatal morbidity is understudied. The Consortium on Safe Labor, a retrospective cohort (2002-2008), included 223,512 singleton deliveries of which 0.2% had hyperthyroidism, 1.4% primary and 0.1% iatrogenic hypothyroidism, and 1.3% other/unspecified thyroid disease. Logistic regression with generalized estimating equations estimated adjusted odds ratios of adverse outcomes. Intensive care treatment was more common for neonates of women with thyroid disease. Hyperthyroidism and primary hypothyroidism were associated with sepsis, respiratory distress syndrome, transient tachypnea, and apnea. Iatrogenic hypothyroidism was associated with sepsis and neonatal anemia. Hyperthyroidism was also associated with rare outcomes (prevalence, <1%) including cardiomyopathy, retinopathy of prematurity, and neonatal thyroid diseases. Hyperthyroid non-Hispanic black women had higher odds of term infants that weighed <2,500 g, and hypothyroid non-Hispanic white women had higher odds of large-for-gestational-age infants. These analyses were stratified by race/ethnicity due to interaction. Associations were similar in analyses restricted to term infants. In conclusion, thyroid diseases were associated with increased neonatal morbidity. Although we lacked data on treatment during pregnancy, these nationwide data suggest a need for better thyroid disease management to reduce neonatal morbidity.
C1 [Maennistoe, Tuija; Mendola, Pauline; Laughon, S. Katherine] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD 20852 USA.
[Reddy, Uma] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, Ctr Dev Biol & Perinatal Med, NIH, Rockville, MD 20852 USA.
RP Mannisto, T (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd,7B05, Rockville, MD 20852 USA.
EM mannistoti@mail.nih.gov
OI Mannisto, Tuija/0000-0002-6382-9153; Mendola,
Pauline/0000-0001-5330-2844; Grantz, Katherine/0000-0003-0276-8534
FU Intramural Research Program of the National Institutes of Health, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development; Intramural Research Program of the Eunice Kennedy Shriver
National Institute of Child Health and Human Development, National
Institutes of Health [HHSN267200603425C]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development.; The data included in this paper
were obtained from the Consortium on Safe Labor, which was supported by
the Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health, through contract HHSN267200603425C. The institutions involved in
the Consortium include the following, in alphabetical order: Baystate
Medical Center, Springfield, Massachusetts; Cedars-Sinai Medical Center
Burnes Allen Research Center, Los Angeles, California; Christiana Care
Health System, Newark, Delaware; George-town University Hospital,
MedStar Health, Washington, DC; Indiana University Clarian Health,
Indianapolis, Indiana; Intermountain Healthcare and the University of
Utah, Salt Lake City, Utah; Maimonides Medical Center, Brooklyn, New
York; MetroHealth Medical Center, Cleveland, Ohio; Summa Health System,
Akron City Hospital, Akron, Ohio; The EMMES Corporation, Rockville,
Maryland (Data Coordinating Center); University of Illinois at Chicago,
Chicago, Illinois; University of Miami, Miami, Florida; and University
of Texas Health Science Center at Houston, Houston, Texas.
NR 35
TC 14
Z9 16
U1 1
U2 18
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 SEP 1
PY 2013
VL 178
IS 5
BP 731
EP 740
DI 10.1093/aje/kwt031
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 211YX
UT WOS:000323949800009
PM 23666815
ER
PT J
AU Rodriguez, AC
Solomon, D
Herrero, R
Hildesheim, A
Gonzalez, P
Wacholder, S
Porras, C
Jimenez, S
Schiffman, M
AF Cecilia Rodriguez, Ana
Solomon, Diane
Herrero, Rolando
Hildesheim, Allan
Gonzalez, Paula
Wacholder, Sholom
Porras, Carolina
Jimenez, Silvia
Schiffman, Mark
CA CVT Grp
TI Impact of Human Papillomavirus Vaccination on Cervical Cytology
Screening, Colposcopy, and Treatment
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE cervical cancer; HPV; HPV vaccination; human papillomavirus; screening
ID HPV-16/18 AS04-ADJUVANTED VACCINE; BLIND PATRICIA TRIAL; OF-STUDY
ANALYSIS; YOUNG-WOMEN; COSTA-RICA; GUANACASTE; INFECTION; EFFICACY;
SYSTEM
AB The impact of human papillomavirus (HPV) vaccination on cervical screening, colposcopy, and treatment is incompletely understood. In 2004-2005, investigators in the Costa Rica Vaccine Trial randomized 7,466 women aged 1825 years, 1: 1, to receive HPV vaccination or hepatitis A vaccination. The worst-ever cytology diagnosis and the 4-year cumulative proportions of colposcopy referral and treatment by vaccination arm were compared for 2 cohorts. The total vaccinated cohort included 6,844 women who provided cervical samples. The naive cohort included 2,284 women with no evidence of previous HPV exposure. In the total vaccinated cohort, HPV-vaccinated women had a significant (P = 0.01) reduction in cytological abnormalities: 12.4% for high-grade lesions and 5.9% for minor lesions. Colposcopy referral was reduced by 7.9% (P = 0.03) and treatment by 11.3% (P = 0.24). Greater relative reductions in abnormal cytology (P < 0.001) were observed for HPV-vaccinated women in the naive cohort: 49.2% for high-grade lesions and 18.1% for minor lesions. Colposcopy referral and treatment were reduced by 21.3% (P = 0.01) and 45.6% (P = 0.08), respectively, in the naive cohort. The overall impact on health services will be modest in the first years after vaccine introduction among young adult women, even in regions with high coverage.
C1 [Cecilia Rodriguez, Ana; Herrero, Rolando; Gonzalez, Paula; Porras, Carolina; Jimenez, Silvia] INCIENSA Fdn, Guanacaste Epidemiol Project, San Jose, Costa Rica.
[Solomon, Diane; Hildesheim, Allan; Wacholder, Sholom; Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Herrero, Rolando; Gonzalez, Paula] Int Agcy Res Canc, Prevent & Implementat Grp, F-69372 Lyon, France.
RP Rodriguez, AC (reprint author), INCIENSA Fdn, Guanacaste Epidemiol Project, Torre La Sabana, San Jose, Costa Rica.
EM acrodriguez@racsa.co.cr
RI Hildesheim, Allan/B-9760-2015
OI Hildesheim, Allan/0000-0003-0257-2363
FU NCI [N01-CP-11005]; Office of Research on Women's Health, US National
Institutes of Health
FX The Costa Rica Vaccine Trial was part of a longstanding collaboration
between investigators in Costa Rica and the US National Cancer Institute
(NCI), was sponsored and funded by the NCI (contract N01-CP-11005) with
support from the Office of Research on Women's Health, US National
Institutes of Health, and was conducted in agreement with the Ministry
of Health of Costa Rica. Vaccine for the trial was provided by
GlaxoSmithKline Biologicals (Rixensart, Belgium) under a Clinical Trials
Agreement with the NCI. GlaxoSmithKline Biologicals also provided
support for aspects of the trial associated with the regulatory
submission needs of the company.
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PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD SEP 1
PY 2013
VL 178
IS 5
BP 752
EP 760
DI 10.1093/aje/kwt047
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 211YX
UT WOS:000323949800011
PM 23843026
ER
PT J
AU Park, SL
Cheng, I
Pendergrass, SA
Kucharska-Newton, AM
Lim, U
Ambite, JL
Caberto, CP
Monroe, KR
Schumacher, F
Hindorff, LA
Oetjens, MT
Wilson, S
Goodloe, RJ
Love, SA
Henderson, BE
Kolonel, LN
Haiman, CA
Crawford, DC
North, KE
Heiss, G
Ritchie, MD
Wilkens, LR
Le Marchand, L
AF Park, Sungshim Lani
Cheng, Iona
Pendergrass, Sarah A.
Kucharska-Newton, Anna M.
Lim, Unhee
Ambite, Jose Luis
Caberto, Christian P.
Monroe, Kristine R.
Schumacher, Fredrick
Hindorff, Lucia A.
Oetjens, Matthew T.
Wilson, Sarah
Goodloe, Robert J.
Love, Shelly-Ann
Henderson, Brian E.
Kolonel, Laurence N.
Haiman, Christopher A.
Crawford, Dana C.
North, Kari E.
Heiss, Gerardo
Ritchie, Marylyn D.
Wilkens, Lynne R.
Le Marchand, Loic
TI Association of the FTO Obesity Risk Variant rs8050136 With Percentage of
Energy Intake From Fat in Multiple Racial/Ethnic Populations
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE energy intake; fat mass and obesity-associated (FTO) gene; obesity;
percent calories from fat; race/ethnicity
ID BODY-MASS INDEX; DIETARY-INTAKE; FOOD-INTAKE; EPIDEMIOLOGY PAGE;
GENE-EXPRESSION; LOCI; BMI; EXPENDITURE; TRAITS; HEALTH
AB Common obesity risk variants have been associated with macronutrient intake; however, these associations' generalizability across populations has not been demonstrated. We investigated the associations between 6 obesity risk variants in (or near) the NEGR1, TMEM18, BDNF, FTO, MC4R, and KCTD15 genes and macronutrient intake (carbohydrate, protein, ethanol, and fat) in 3 Population Architecture using Genomics and Epidemiology (PAGE) studies: the Multiethnic Cohort Study (1993-2006) (n = 19,529), the Atherosclerosis Risk in Communities Study (1987-1989) (n = 11,114), and the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) Study, which accesses data from the Third National Health and Nutrition Examination Survey (1991-1994) (n = 6,347). We used linear regression, with adjustment for age, sex, and ethnicity, to estimate the associations between obesity risk genotypes and macronutrient intake. A fixed-effects meta-analysis model showed that the FTO rs8050136 A allele (n = 36,973) was positively associated with percentage of calories derived from fat (beta(meta) = 0.2244 (standard error, 0.0548); P = 4 x10(-5)) and inversely associated with percentage of calories derived from carbohydrate (beta(meta) = -0.2796 (standard error, 0.0709); P = 8 x 10(-5)). In the Multiethnic Cohort Study, percentage of calories from fat assessed at baseline was a partial mediator of the rs8050136 effect on body mass index (weight (kg)/height (m)(2)) obtained at 10 years of follow-up (mediation of effect = 0.0823 kg/m(2),95% confidence interval: 0.0559, 0.1128). Our data provide additional evidence that the association of FTO with obesity is partially mediated by dietary intake.
C1 [Park, Sungshim Lani; Lim, Unhee; Caberto, Christian P.; Kolonel, Laurence N.; Wilkens, Lynne R.; Le Marchand, Loic] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96813 USA.
[Cheng, Iona] Canc Prevent Inst Calif, Fremont, CA USA.
[Pendergrass, Sarah A.; Ritchie, Marylyn D.] Penn State Univ, Ctr Syst Genom, Dept Biochem & Mol Biol, University Pk, PA 16802 USA.
[Kucharska-Newton, Anna M.; Love, Shelly-Ann; North, Kari E.; Heiss, Gerardo] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
[Ambite, Jose Luis] Univ So Calif, Inst Informat Sci, Marina Del Rey, CA 90292 USA.
[Monroe, Kristine R.; Schumacher, Fredrick; Henderson, Brian E.; Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Hindorff, Lucia A.] NHGRI, Off Populat Genom, NIH, Bethesda, MD 20892 USA.
[Oetjens, Matthew T.; Wilson, Sarah; Goodloe, Robert J.; Crawford, Dana C.] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN 37235 USA.
[Crawford, Dana C.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37235 USA.
[North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA.
RP Park, SL (reprint author), Univ Hawaii, Ctr Canc, Program Epidemiol, 701 Ilalo St,5th Floor, Honolulu, HI 96813 USA.
EM lpark@cc.hawaii.edu
FU National Human Genome Research Institute (NHGRI); Genetic Epidemiology
of Causal Variants Across the Life Course (CALiCo) Consortium
[U01HG004803]; Epidemiologic Architecture for Genes Linked to
Environment (EAGLE) Study [U01HG004798]; Multiethnic Cohort (MEC) Study
[U01HG004802]; Women's Health Initiative [U01HG004790]; PAGE
Coordinating Center [U01HG004801, U01HG 004801]; NHGRI PAGE Study
[U01HG004803, U01HG004798, U01HG004802]; Centers for Disease Control and
Prevention; National Cancer Institute [R37CA54281, R01 CA63, P01CA33619,
U01CA136792, U01CA98758]; National Heart, Lung, and Blood Institute
[HHSN268201100005C, HHSN26820 1100006C, HSN268201100007C,
HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN26820
1100011C, HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694];
NHGRI [U01HG004402]; National Institutes of Health (NIH)
[HHSN268200625226C]; [UL1RR025005]
FX The Population Architecture using Genomics and Epidemiology (PAGE) Study
is funded by the National Human Genome Research Institute (NHGRI),
supported by grants U01HG004803 (Genetic Epidemiology of Causal Variants
Across the Life Course (CALiCo) Consortium), U01HG004798 (Epidemiologic
Architecture for Genes Linked to Environment (EAGLE) Study), U01HG004802
(Multiethnic Cohort (MEC) Study), U01HG004790 (Women's Health
Initiative), and U01HG004801 (PAGE Coordinating Center), and their
respective NHGRI American Recovery and Reinvestment Act (ARRA)
supplements. The data and materials included in this report resulted
from a collaboration between the following studies: The EAGLE Study is
funded through the NHGRI PAGE Study (grant U01HG004798-01 and its NHGRI
ARRA supplement). The study participants were derived from the Third
National Health and Nutrition Examination Survey, which is supported by
the Centers for Disease Control and Prevention. The MEC characterization
of epidemiologic architecture is funded through the NHGRI PAGE Study
(grant U01HG004802 and its NHGRI ARRA supplement). The MEC Study is
funded by the National Cancer Institute (grants R37CA54281, R01 CA63,
P01CA33619, U01CA136792, and U01CA98758). Funding for CALiCo was
provided through the NHGRI PAGE Study (grant U01HG004803). The
Atherosclerosis Risk in Communities (ARIC) Study is carried out as a
collaborative study supported by National Heart, Lung, and Blood
Institute contracts HHSN268201100005C, HHSN26820 1100006C,
HSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN26820 1100011C, and HHSN268201100012C; National
Heart, Lung, and Blood Institute grants R01HL087641, R01HL59367, and
R01HL086694; NHGRI contract U01HG004402; and National Institutes of
Health (NIH) contract HHSN268200625226C. The infrastructure of the ARIC
Study was partly supported by grant UL1RR025005, a component of the NIH
and the NIH Roadmap for Medical Research. Assistance with phenotype
harmonization, single-nucleotide polymorphism selection and annotation,
data-cleaning, data management, integration, and dissemination, and
general study coordination was provided by the PAGE Coordinating Center
(grant U01HG 004801). The National Institute of Mental Health also
contributes support for the Coordinating Center.
NR 58
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PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD SEP 1
PY 2013
VL 178
IS 5
BP 780
EP 790
DI 10.1093/aje/kwt028
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 211YX
UT WOS:000323949800014
PM 23820787
ER
PT J
AU Mondul, AM
Giovannucci, E
Platz, EA
AF Mondul, Alison M.
Giovannucci, Edward
Platz, Elizabeth A.
TI A Prospective Study of Statin Drug Use and Lower Urinary Tract Symptoms
in Older Men
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE cohort; lower urinary tract symptoms; risk; statin drug
ID BENIGN PROSTATIC HYPERPLASIA; RISK; ENLARGEMENT; ASSOCIATION; CANCER;
INDEX
AB Dyslipidemia and chronic inflammation may play a role in the cause of lower urinary tract symptoms (LUTS) in older men. Use of statin drugs, which are prescribed to lower cholesterol and appear to reduce inflammation, may decrease the incidence or progression of LUTS. The associations of statin drug use with LUTS incidence and progression were prospectively evaluated in the Health Professionals Follow-up Study from 1992 to 2008. Hazard ratios and 95% confidence intervals of incident LUTS (from no or a low International Prostate Symptom Score (IPSS) of 0-7 to a moderate or worse IPSS of >= 15; n = 5,790 cases in 24,715 men) and of LUTS progression (from modest IPSS of 8-14 to severe IPSS of >= 20; n = 2,238 cases in 8,709 men) were calculated comparing current statin use with nonuse. The hazard ratios of LUTS incidence and progression comparing current use to nonuse were greater than 1. However, when comparisons were restricted to participants who used drugs to treat hypertension (a surrogate for uptake of medical care), statin use was not associated with LUTS incidence (hazard ratio = 1.02, 95% confidence interval: 0.94, 1.12) or progression (hazard ratio = 0.98, 95% confidence interval: 0.85, 1.13). Thus, statin use is unlikely to beneficially influence the development or course of LUTS. The present study highlights a methodological issue (confounding) that must be addressed in observational studies on the use of common drugs for indications other than the primary use.
C1 [Mondul, Alison M.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Giovannucci, Edward] Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA.
[Giovannucci, Edward] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Platz, Elizabeth A.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Platz, Elizabeth A.] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA.
[Platz, Elizabeth A.] Johns Hopkins Univ, Sch Med, Brady Urol Res Inst, Baltimore, MD USA.
RP Mondul, AM (reprint author), 9609 Med Ctr Dr,Room 6E328, Rockville, MD 20850 USA.
EM mondulam@mail.nih.gov
OI Mondul, Alison/0000-0002-8843-1416
FU Urologic Diseases in America Project [N01 DK70003]; Public Health
Service from the National Institutes of Health, Department of Health and
Human Services [R01 DK45779, P01 CA55075, P50 DK82998]
FX This study was supported by The Urologic Diseases in America Project
(grant N01 DK70003) and by Public Health Service grants R01 DK45779
(Harvard), P01 CA55075 (Harvard), and P50 DK82998 (Hopkins) from the
National Institutes of Health, Department of Health and Human Services.
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U1 0
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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 SEP 1
PY 2013
VL 178
IS 5
BP 797
EP 803
DI 10.1093/aje/kwt055
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 211YX
UT WOS:000323949800016
PM 23847173
ER
PT J
AU Ferreccio, C
Smith, AH
Duran, V
Barlaro, T
Benitez, H
Valdes, R
Aguirre, JJ
Moore, LE
Acevedo, J
Vasquez, MI
Perez, L
Yuan, Y
Liaw, J
Cantor, KP
Steinmaus, C
AF Ferreccio, Catterina
Smith, Allan H.
Duran, Viviana
Barlaro, Teresa
Benitez, Hugo
Valdes, Rodrigo
Jose Aguirre, Juan
Moore, Lee E.
Acevedo, Johanna
Isabel Vasquez, Maria
Perez, Liliana
Yuan, Yan
Liaw, Jane
Cantor, Kenneth P.
Steinmaus, Craig
TI Case-Control Study of Arsenic in Drinking Water and Kidney Cancer in
Uniquely Exposed Northern Chile
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE arsenic; case-control; Chile; drinking water; kidney cancer
ID CIGARETTE-SMOKING; LUNG-CANCER; MORTALITY; TOXICITY; BLADDER
AB Millions of people worldwide are exposed to arsenic in drinking water. The International Agency for Research on Cancer has concluded that ingested arsenic causes lung, bladder, and skin cancer. However, a similar conclusion was not made for kidney cancer because of a lack of research with individual data on exposure and dose-response. With its unusual geology, high exposures, and good information on past arsenic water concentrations, northern Chile is one of the best places in the world to investigate the carcinogenicity of arsenic. We performed a case-control study in 2007-2010 of 122 kidney cancer cases and 640 population-based controls with individual data on exposure and potential confounders. Cases included 76 renal cell, 24 transitional cell renal pelvis and ureter, and 22 other kidney cancers. For renal pelvis and ureter cancers, the adjusted odds ratios by average arsenic intakes of <400, 400-1,000, and >1,000 mu g/day (median water concentrations of 60, 300, and 860 mu g/L) were 1.00, 5.71 (95% confidence interval: 1.65, 19.82), and 11.09 (95% confidence interval: 3.60, 34.16) (P-trend < 0.001), respectively. Odds ratios were not elevated for renal cell cancer. With these new findings, including evidence of dose-response, we believe there is now sufficient evidence in humans that drinking-water arsenic causes renal pelvis and ureter cancer.
C1 [Ferreccio, Catterina; Acevedo, Johanna; Perez, Liliana] Pontificia Univ Catolica Chile, Dept Salud Publ, Santiago, Chile.
[Smith, Allan H.; Yuan, Yan; Liaw, Jane; Steinmaus, Craig] Univ Calif Berkeley, Sch Publ Hlth, Arsen Res Grp, Berkeley, CA 94720 USA.
[Duran, Viviana; Barlaro, Teresa] Hosp Reg Iquique, Unidad Anat Patol, Iquique, Chile.
[Benitez, Hugo] Hosp Reg Antofagasta, Unidad Anat Patol, Antofagasta, Chile.
[Valdes, Rodrigo] Histonor Ltda, Labs Anat Patol, Antofagasta, Chile.
[Jose Aguirre, Juan] Citonet Ltda, Labs Anat Patol, Antofagasta, Chile.
[Moore, Lee E.; Cantor, Kenneth P.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Isabel Vasquez, Maria] Univ Tarapaca, Arica, Chile.
[Steinmaus, Craig] Calif Environm Protect Agcy, Off Environm Hlth Hazard Assessment, Oakland, CA USA.
RP Steinmaus, C (reprint author), Univ Calif Berkeley, Sch Publ Hlth, 50 Univ Hall,MC7360, Berkeley, CA 94720 USA.
EM craigs@berkeley.edu
FU US National Institute of Environmental Health Sciences [R01 ES014032-01,
P42 ES04705]
FX This work was supported by grants R01 ES014032-01 and P42 ES04705 from
the US National Institute of Environmental Health Sciences.
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U2 35
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 SEP 1
PY 2013
VL 178
IS 5
BP 813
EP 818
DI 10.1093/aje/kwt059
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 211YX
UT WOS:000323949800018
PM 23764934
ER
PT J
AU Freeman, LEB
Blair, A
Lubin, JH
Stewart, PA
Hayes, RB
Hoover, RN
Hauptmann, M
AF Freeman, Laura E. Beane
Blair, Aaron
Lubin, Jay H.
Stewart, Patricia A.
Hayes, Richard B.
Hoover, Robert N.
Hauptmann, Michael
TI Mortality from solid tumors among workers in formaldehyde industries: An
update of the NCI cohort
SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE
LA English
DT Article
DE formaldehyde; cancer; epidemiology
ID NATIONAL-CANCER-INSTITUTE; OCCUPATIONAL RISK-FACTORS; SQUAMOUS-CELL
CARCINOMA; JOB-EXPOSURE MATRIX; NASOPHARYNGEAL CANCER; LUNG-CANCER;
CHEMICAL WORKERS; SINONASAL CANCER; UNITED-STATES; NASAL CAVITY
AB Background Formaldehyde, a widely used chemical, is considered a human carcinogen.
Methods We extended follow-up of the largest industrial cohort of workers in formaldehyde industries (n=25,619) by 10 years through 2004. Standardized mortality ratios (SMRs) and rate ratios (RRs) were calculated for deaths from solid tumors using quantitative formaldehyde exposure estimates.
Results During 998,239 person-years, 13,951 deaths occurred. With one additional death, previously observed excesses for nasopharyngeal cancer (n=10) persisted for peak, average intensity and cumulative exposure; RRs in the highest exposure categories were 7.66 (95% CI: 0.94, 62.34), P-trend=0.005, 11.54 (95% CI: 1.38, 96.81), P-trend=0.09, and 2.94 (95% CI: 0.65, 13.28), P-trend=0.06, respectively. For all cancer, solid tumors and lung cancer, SMRs among exposed workers were elevated, but internal analyses revealed no positive associations with formaldehyde exposure.
Conclusions Consistent with previous analyses of this cohort, this update continues to suggest a link between formaldehyde exposure and nasopharyngeal cancer. Am. J. Ind. Med. 56:1015-1026, 2013. (c) 2013 Wiley Periodicals, Inc.
C1 [Freeman, Laura E. Beane; Blair, Aaron] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,US Dept HHS, Bethesda, MD 20892 USA.
[Lubin, Jay H.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,US Dept HHS, Bethesda, MD 20892 USA.
[Stewart, Patricia A.] Stewart Exposure Assessments LLC, Arlington, VA USA.
[Hayes, Richard B.] NYU Med Ctr, Dept Environm Med, Div Epidemiol, New York, NY 10016 USA.
[Hoover, Robert N.] Div Canc Epidemiol & Genet, Epidemiol & Biostat Program, Bethesda, MD USA.
[Hauptmann, Michael] Netherlands Canc Inst, Dept Epidemiol & Biostat, Amsterdam, Netherlands.
RP Freeman, LEB (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,US Dept HHS, Bethesda, MD 20892 USA.
EM freemala@mail.nih.gov
OI Hayes, Richard/0000-0002-0918-661X
FU Intramural Research Program of the National Cancer Institute
FX Contract grant sponsor: Intramural Research Program of the National
Cancer Institute.
NR 61
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U1 1
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0271-3586
EI 1097-0274
J9 AM J IND MED
JI Am. J. Ind. Med.
PD SEP
PY 2013
VL 56
IS 9
BP 1015
EP 1026
DI 10.1002/ajim.22214
PG 12
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 200XX
UT WOS:000323106000004
ER
PT J
AU Beck, L
Bomback, AS
Choi, MJ
Holzman, LB
Langford, C
Mariani, LH
Somers, MJ
Trachtman, H
Waldman, M
AF Beck, Laurence
Bomback, Andrew S.
Choi, Michael J.
Holzman, Larry B.
Langford, Carol
Mariani, Laura H.
Somers, Michael J.
Trachtman, Howard
Waldman, Meryl
TI KDOQI US Commentary on the 2012 KDIGO Clinical Practice Guideline for
Glomerulonephritis
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Editorial Material
ID RANDOMIZED CONTROLLED-TRIAL; IDIOPATHIC MEMBRANOUS NEPHROPATHY; FOCAL
SEGMENTAL GLOMERULOSCLEROSIS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; DENSE
DEPOSIT DISEASE; ACUTE-RENAL-FAILURE; RESISTANT NEPHROTIC SYNDROME;
MINIMAL-CHANGE DISEASE; ANTIBODY-ASSOCIATED VASCULITIS; ANCA-ASSOCIATED
VASCULITIS
AB Glomerulonephritis (GN) is an important cause of morbidity and mortality in patients of all ages throughout the world. Because these disorders are relatively rare, it is difficult to perform randomized clinical trials to define optimal treatment for many of the specific glomerulopathies. In the absence of high-grade evidence to guide the care of glomerular diseases, in June 2012, KDIGO (Kidney Disease: Improving Global Outcomes) published an international clinical guideline for GN. The Work Group report represents an important review of the literature in this area and offers valid and useful guidelines for the most common situations that arise in the management of patients with glomerular disease. This commentary, developed by a panel of clinical experts convened by the National Kidney Foundation, attempts to put the GN guideline into the context of the US health care system. Overall, we support the vast majority of the recommendations and highlight select areas in which epidemiological factors and medical practice patterns in this country justify modifications and adjustments in order to achieve favorable outcomes. There remain large gaps in our knowledge of the best approaches to treat glomerular disease and we strongly endorse an expanded clinical research effort to improve the health and long-term outcomes of children and adults with GN. (C) 2013 by the National Kidney Foundation, Inc.
C1 [Beck, Laurence] Boston Univ Sch Med, Boston, MA USA.
[Bomback, Andrew S.] Columbia Univ Med Ctr, New York, NY USA.
[Choi, Michael J.] Johns Hopkins Univ Sch Med, Baltimore, MD USA.
[Holzman, Larry B.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Langford, Carol] Cleveland Clin, Cleveland, OH 44106 USA.
[Mariani, Laura H.] Univ Michigan Sch Med, Ann Arbor, MI USA.
[Somers, Michael J.] Boston Childrens Hosp, Boston, MA USA.
[Trachtman, Howard] New York Univ Langone Med Ctr, New York, NY USA.
[Waldman, Meryl] NIDDK, NIH, Bethesda, MD USA.
RP Choi, MJ (reprint author), Johns Hopkins Univ, Div Nephrol, Dept Med, 1830 E Monument St,Ste 416, Baltimore, MD 21287 USA.
EM mchoi3@jhmi.edu
OI Beck, Laurence/0000-0003-1482-4089; Trachtman,
Howard/0000-0001-7447-9489
NR 206
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U1 2
U2 16
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD SEP
PY 2013
VL 62
IS 3
BP 403
EP 441
DI 10.1053/j.ajkd.2013.06.002
PG 39
WC Urology & Nephrology
SC Urology & Nephrology
GA 212ZZ
UT WOS:000324023700002
PM 23871408
ER
PT J
AU Kasiske, BL
Anderson-Haag, T
Ibrahim, HN
Pesavento, TE
Weir, MR
Nogueira, JM
Cosio, FG
Kraus, ES
Rabb, HH
Kalil, RS
Posselt, AA
Kimmel, PL
Steffes, MW
AF Kasiske, Bertram L.
Anderson-Haag, Teresa
Ibrahim, Hassan N.
Pesavento, Todd E.
Weir, Matthew R.
Nogueira, Joseph M.
Cosio, Fernando G.
Kraus, Edward S.
Rabb, Hamid H.
Kalil, Roberto S.
Posselt, Andrew A.
Kimmel, Paul L.
Steffes, Michael W.
TI A Prospective Controlled Study of Kidney Donors: Baseline and 6-Month
Follow-up
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Chronic kidney disease; unilateral nephrectomy; glomerular filtration
rate; patient safety; mineral and bone disorders
ID GLOMERULAR-FILTRATION-RATE; STAGE RENAL-DISEASE; SINGLE-CENTER
EXPERIENCE; LONG-TERM CONSEQUENCES; SERUM URIC-ACID; INSULIN-RESISTANCE;
UNILATERAL NEPHRECTOMY; MINERAL METABOLISM; CYSTATIN C;
CARDIOVASCULAR-DISEASE
AB Background: Most previous studies of living kidney donors have been retrospective and have lacked suitable healthy controls. Needed are prospective controlled studies to better understand the effects of a mild reduction in kidney function from kidney donation in otherwise healthy individuals.
Study Design: Prospective, controlled, observational cohort study.
Setting & Participants: Consecutive patients approved for donation at 8 transplant centers in the United States were asked to participate. For every donor enrolled, an equally healthy control with 2 kidneys who theoretically would have been suitable to donate a kidney also was enrolled.
Predictor: Kidney donation.
Measurements: At baseline predonation and at 6 months after donation, medical history, vital signs, measured (iohexol) glomerular filtration rate, and other measurements were collected. There were 201 donors and 198 controls who completed both baseline and 6-month visits and form the basis of this report.
Results: Compared with controls, donors had 28% lower glomerular filtration rates at 6 months (94.6 +/- 15.1 [SD] vs 67.6 +/- 10.1 mL/min/1.73 m(2); P < 0.001), associated with 23% greater parathyroid hormone (42.8 +/- 15.6 vs 52.7 +/- 20.9 pg/mL; P < 0.001), 5.4% lower serum phosphate (3.5 +/- 0.5 vs 3.3 +/- 0.5 mg/dL; P < 0.001), 3.7% lower hemoglobin (13.6 +/- 1.4 vs 13.1 +/- 1.2 g/dL; P < 0.001), 8.2% greater uric acid (4.9 +/- 1.2 vs 5.3 +/- 1.1 mg/dL; P < 0.001), 24% greater homocysteine (1.2 +/- 0.3 vs 1.5 +/- 0.4 mg/L; P < 0.001), and 1.5% lower high-density lipoprotein cholesterol (54.9 +/- 16.4 vs 54.1 +/- 13.9 mg/dL; P = 0.03) levels. There were no differences in albumin-creatinine ratios (5.0 [IQR, 4.0-6.6] vs 5.0 [IQR, 3.3-5.4] mg/g; P = 0.5), office blood pressures, or glucose homeostasis.
Limitations: Short duration of follow-up and possible bias resulting from an inability to screen controls with kidney and vascular imaging performed in donors.
Conclusions: Kidney donors have some, but not all, abnormalities typically associated with mild chronic kidney disease 6 months after donation. Additional follow-up is warranted. (C) 2013 by the National Kidney Foundation, Inc.
C1 [Kasiske, Bertram L.; Anderson-Haag, Teresa] Hennepin Cty Med Ctr, Dept Med, Minneapolis, MN 55415 USA.
[Ibrahim, Hassan N.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA.
[Pesavento, Todd E.] Ohio State Univ, Dept Med, Columbus, OH 43210 USA.
[Weir, Matthew R.; Nogueira, Joseph M.] Univ Maryland Sch Med, Dept Med, Baltimore, MD USA.
[Cosio, Fernando G.] Mayo Clin, Dept Med, Rochester, MN USA.
[Kraus, Edward S.; Rabb, Hamid H.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Kalil, Roberto S.] Univ Iowa, Dept Med, Iowa City, IA 52242 USA.
[Posselt, Andrew A.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA.
[Kimmel, Paul L.] NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD USA.
[Steffes, Michael W.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
RP Kasiske, BL (reprint author), Hennepin Cty Med Ctr, Dept Med, 701 Pk Ave, Minneapolis, MN 55415 USA.
EM kasis001@umn.edu
FU National Institutes of Health [U01 DK066013]; Minneapolis Medical
Research Foundation, Minneapolis, MN
FX This study was funded by the National Institutes of Health under
cooperative agreement U01 DK066013, Paul L. Kimmel, MD, Project Officer.
It was also supported by funds from the Minneapolis Medical Research
Foundation, Minneapolis, MN.
NR 70
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U2 20
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD SEP
PY 2013
VL 62
IS 3
BP 577
EP 586
DI 10.1053/j.ajkd.2013.01.027
PG 10
WC Urology & Nephrology
SC Urology & Nephrology
GA 212ZZ
UT WOS:000324023700019
PM 23523239
ER
PT J
AU St Peter, WL
Weinhandl, ED
Flessner, MF
AF St Peter, Wendy L.
Weinhandl, Eric D.
Flessner, Michael F.
TI In Reply to 'Primary Objective of Study of Sitagliptin in Patients With
ESRD on Dialysis'
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Letter
C1 [St Peter, Wendy L.] Univ Minnesota, Coll Pharm, Minneapolis, MN 55455 USA.
[St Peter, Wendy L.; Weinhandl, Eric D.] Minneapolis Med Res Fdn Inc, Minneapolis, MN USA.
[Flessner, Michael F.] NIH, Bethesda, MD 20892 USA.
RP St Peter, WL (reprint author), Univ Minnesota, Coll Pharm, Minneapolis, MN 55455 USA.
OI St Peter, Wendy/0000-0002-2201-3019
NR 4
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 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD SEP
PY 2013
VL 62
IS 3
BP 642
EP 643
DI 10.1053/j.ajkd.2013.06.009
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA 212ZZ
UT WOS:000324023700028
PM 23972059
ER
PT J
AU Baxter, SL
Pistilli, M
Pujari, SS
Liesegang, TL
Suhler, EB
Thorne, JE
Foster, CS
Jabs, DA
Levy-Clarke, GA
Nussenblatt, RB
Rosenbaum, JT
Kempen, JH
AF Baxter, Sally L.
Pistilli, Maxwell
Pujari, Siddharth S.
Liesegang, Teresa L.
Suhler, Eric B.
Thorne, Jennifer E.
Foster, C. Stephen
Jabs, Douglas A.
Levy-Clarke, Grace A.
Nussenblatt, Robert B.
Rosenbaum, James T.
Kempen, John H.
TI Risk of Choroidal Neovascularization among the Uveitides
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID PUNCTATE INNER CHOROIDOPATHY; INTRAVITREAL BEVACIZUMAB; MULTIFOCAL
CHOROIDITIS; REGRESSION-ANALYSIS; DISEASES; VEGF; COMPLICATIONS;
NOMENCLATURE; PANUVEITIS; SECONDARY
AB PURPOSE: To evaluate the risk, risk factors, and visual impact of choroidal neovascularization (CNV) in uveitis cases.
DESIGN: Retrospective cohort study.
METHODS: Standardized medical record review at 5 tertiary centers.
RESULTS: Among 15 137 uveitic eyes (8868 patients), CNV was rare in the cases of anterior or intermediate uveitis. Among the 4041 eyes (2307 patients) with posterior uveitis or panuveitis, 81(2.0%) had CNV at presentation. Risk factors included posterior uveitis in general and specific uveitis syndromes affecting the outer retina retinal pigment epithelium choroid interface. Among the 2364 eyes (1357 patients) with posterior uveitis or panuveitis and free of CNV at the time of cohort entry, the cumulative 2-year incidence of CNV was 2.7% (95% confidence interval [CI], 1.8% to 3.5%). Risk factors for incident CNV included currently active inflammation (adjusted hazard ratio [aHR], 2.13; 95% CI, 1.26 to 3.60), preretinal neovascularization (aHR, 3.19; 95% CI, 1.30 to 7.80), and prior diagnosis of CNV in the contralateral eye (aHR, 5.79; 95% CI, 2.77 to 12.09). Among specific syndromes, the incidence was greater in Vogt-Koyanagi-Harada syndrome (aHR, 3.37; 95% CI, 1.52 to 7.46) and punctate inner choroiditis (aHR, 8.67; 95% CI, 2.83 to 26.54). Incident CNV was associated with a 2-line loss of visual acuity (+0.19 logarithm of the minimal angle of resolution units; 95% CI, 0.079 to 0.29) from the preceding visit.
CONCLUSIONS: CNV is an uncommon complication Of uveitis associated with visual impairment that occurs more commonly in forms affecting the outer retina retinal pigment epithelium choroid interface, during periods of inflammatory activity, in association with preretinal neovascularization, and in second eyes of patients with unilateral CNV. Because CNV is treatable, a systematic approach to early detection in high-risk patients may be appropriate. ((C) 2013 by Elsevier Inc. All rights reserved.)
C1 [Baxter, Sally L.; Kempen, John H.] Univ Penn, Perelman Sch Med, Scheie Eye Inst, Philadelphia, PA 19104 USA.
[Pistilli, Maxwell; Kempen, John H.] Univ Penn, Perelman Sch Med, Ctr Prevent Ophthalmol & Biostat, Dept Ophthalmol, Philadelphia, PA 19104 USA.
[Pujari, Siddharth S.; Foster, C. Stephen] Massachusetts Eye Res & Surg Inst, Cambridge, MA USA.
[Pujari, Siddharth S.] Vasan Eye Care Hosp, Belgaum, Karnataka, India.
[Liesegang, Teresa L.; Suhler, Eric B.; Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA.
[Suhler, Eric B.; Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA.
[Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA.
[Thorne, Jennifer E.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA.
[Thorne, Jennifer E.; Jabs, Douglas A.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Foster, C. Stephen] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA.
[Jabs, Douglas A.] Icahn Sch Med Mt Sinai, Dept Ophthalmol, New York, NY USA.
[Jabs, Douglas A.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY USA.
[Levy-Clarke, Grace A.; Nussenblatt, Robert B.] NEI, Immunol Lab, Bethesda, MD 20892 USA.
[Levy-Clarke, Grace A.] Johnson & Johnson, New Brunswick, NJ USA.
[Rosenbaum, James T.] Legacy Hlth Syst, Devers Eye Inst, Portland, OR USA.
[Kempen, John H.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
RP Kempen, JH (reprint author), Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, 3535 Market St,Suite 700, Philadelphia, PA 19104 USA.
EM john.kempen@uphs.upenn.edu
OI Pistilli, Maxwell/0000-0002-4266-4150
FU Research to Prevent Blindness, Inc, New York, New York; Paul and Evanina
Mackall Foundation; National Eye Institute; Department of Veterans'
Affairs
FX ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE
OF POTENTIAL CONFLICTS OF INTEREST and the following were reported.
Jennifer E. Thome serves a consultant for Allergan and XOMA. C. Stephen
Foster serves as a lecturer for Alcon, Inspire, Ista, and Centocor; as a
Consultant for Sirion; as a consultant and lecturer for Allergan and
Bausch & Lomb; and as an equity owner for EyeGate. Douglas A. Jabs
serves a consultant for Abbott Laboratories, Alcon Laboratories,
Allergan Pharmaceutical Corporation, Corcept Therapeutics, Genentech,
Genzyme Corporation, GlaxoSmith Kline, and Roche Pharmaceuticals and is
a member of the Data and Safety Monitoring Board for Applied Genetic
Technologies Corporation and Novartis Pharmaceutical Corporation. Grace
A. Levy-Clarke is employed by Johnson & Johnson Vision Care. James T.
Rosenbaum serves or has served as a consultant for Abbott Laboratories,
Amgen, Allergan, Genentech, Novartis, and UCB and has been involved in
clinical trials for Abbott Laboratories, Genentech, Lux Biosciences, and
Eyegate Pharma. John H. Kempen serves or has served as a consultant for
Alcon, Allergan, Can-Fite, Clearside, Lux Biosciences, Sanofi-Pasteur,
and Xoma. Supported primarily by Grant EY014943 from the National Eye
Institute, National Institutes of Health, Bethesda, Maryland (J.H.K.).
Additional support was provided by Research to Prevent Blindness, Inc,
New York, New York, and the Paul and Evanina Mackall Foundation. Dr
Kempen was a Research to Prevent Blindness James S Adams Special Scholar
Award recipient, Dr Thome was a Research to Prevent Blindness Harrington
Special Scholar Award recipient, and Drs Jabs and Rosenbaum were
Research to Prevent Blindness Senior Scientific Investigator Award
recipients during the course of the study. Dr Levy-Clarke was previously
supported by and Dr Nussenblatt continues to be supported by intramural
funds from the National Eye Institute. Dr Suhler receives support from
the Department of Veterans' Affairs. None of the sponsors had any role
in the design and conduct of the report; collection, management,
analysis, and interpretation of the data; or in the preparation, review,
and approval of this manuscript. Involved in Design and conduct of study
(S.L.B., M.P., J.H.K.); Collection, management, analysis, and
interpretation of data (all authors); Preparation of manuscript (S.L.B.,
M.P., J.H.K.); and review and approval of manuscript (all authors).
NR 28
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U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD SEP
PY 2013
VL 156
IS 3
BP 468
EP 477
DI 10.1016/j.ajo.2013.04.040
PG 10
WC Ophthalmology
SC Ophthalmology
GA 214RM
UT WOS:000324153500009
PM 23795984
ER
PT J
AU Toy, BC
Krishnadev, N
Indaram, M
Cunningham, D
Cukras, CA
Chew, EY
Wong, WT
AF Toy, Brian C.
Krishnadev, Nupura
Indaram, Maanasa
Cunningham, Denise
Cukras, Catherine A.
Chew, Emily Y.
Wong, Wai T.
TI Drusen Regression is Associated With Local Changes in Fundus
Autofluorescence in Intermediate Age-Related Macular Degeneration
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; SCANNING LASER OPHTHALMOSCOPE; GEOGRAPHIC
ATROPHY; SOFT DRUSEN; BRUCHS MEMBRANE; PIGMENT; PHOTOCOAGULATION;
MACULOPATHY; PATHOGENESIS; MACROPHAGES
AB PURPOSE: To investigate the association of spontaneous drusen regression in intermediate age-related macular degeneration (AMD) with Changes on fundus photography and fundus autofluorescence (FAF) imaging.
DESIGN: Prospective observational case series.
METHODS: Fundus images from 58 eyes (in 58 patients) with intermediate AMD and large drusen were assessed over 2 years for areas of drusen regression that exceeded the area of circle Cl (diameter 125 mu m; Age-Related Eye Disease Study grading protocol). Manual segmentation and computer-based image analysis were used to detect and delineate areas of drusen regression. Delineated regions were graded as to their appearance on fundus photographs and FAF images, and changes in FAF signal were graded manually and quantitated using automated image analysis.
RESULTS: Drusen regression was detected in approximately half of study eyes using manual (48%) and computer-assisted (50%) techniques. At year-2, the clinical appearance of areas of drusen regression on fundus photography was mostly unremarkable, with a majority of eyes (71%) demonstrating no detectable clinical abnormalities, and the remainder (29%) showing minor pigmentary changes. However, drusen regression areas were associated with local changes in FAF that were significantly more prominent than changes on fundus photography. A majority of eyes (64%-66%) demonstrated a predominant decrease in overall FAF signal, while 14%-21% of eyes demonstrated a predominant increase in overall FAF signal.
CONCLUSIONS: FAF imaging demonstrated that drusen regression in intermediate AMD was often accompanied by changes in local autofluorescence signal. Drusen regression may be associated with concurrent structural and physiologic changes in the outer retina. (Published by Elsevier Inc.)
C1 [Toy, Brian C.; Indaram, Maanasa; Wong, Wai T.] NEI, Unit Neuron Glia Interact Retinal Dis, NIH, Bethesda, MD 20892 USA.
[Krishnadev, Nupura; Cukras, Catherine A.; Chew, Emily Y.] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
[Cunningham, Denise] NEI, Off Clin Director, NIH, Bethesda, MD 20892 USA.
RP Wong, WT (reprint author), NEI, Unit Neuron Glia Interact Retinal Dis, NIH, Bldg 6,Room 215, Bethesda, MD 20892 USA.
EM wongw@nei.nih.gov
RI Wong, Wai/B-6118-2017
OI Wong, Wai/0000-0003-0681-4016
FU Clinical Research Training Program; National Institutes of Health
(Bethesda, Maryland, USA); Pfizer Inc (New York, New York, USA);
National Eye Institute Intramural Research Program (Bethesda, Maryland,
USA)
FX ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE
OF POTENTIAL CONFLICTS OF INTEREST. Financial disclosures: B.T. was
supported by the Clinical Research Training Program, a public-private
partnership supported jointly by the National Institutes of Health
(Bethesda, Maryland, USA) and Pfizer Inc (New York, New York, USA; via a
grant to the Foundation for the National Institutes of Health [Bethesda,
Maryland, USA] from Pfizer). The sponsor or funding organization had no
role in the design or conduct of this research. This research was funded
by the National Eye Institute Intramural Research Program (Bethesda,
Maryland, USA). Contributions of authors: design of study (B.T., N.K.,
E.C., W.W.); conduct of study (N.K., D.C., C.C., E.Y., W.W.); analysis
and interpretation of data (B.T., N.K., M.I., W.W.); writing of
manuscript (B.T., N.K., M.I., D.C., C.C., E.Y., W.W.); and final
approval of version to be published (B.T., N.K., M.I., D.C., C.C., E.Y.,
W.W.).
NR 56
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Z9 9
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD SEP
PY 2013
VL 156
IS 3
BP 532
EP 542
DI 10.1016/j.ajo.2013.04.031
PG 11
WC Ophthalmology
SC Ophthalmology
GA 214RM
UT WOS:000324153500015
PM 23830564
ER
PT J
AU Martinez-Anton, A
Sokolowska, M
Kern, S
Davis, AS
Alsaaty, S
Taubenberger, JK
Sun, JF
Cai, RM
Danner, RL
Eberlein, M
Logun, C
Shelhamer, JH
AF Martinez-Anton, Asuncion
Sokolowska, Milena
Kern, Steven
Davis, A. Sally
Alsaaty, Sara
Taubenberger, Jeffery K.
Sun, Junfeng
Cai, Rongman
Danner, Robert L.
Eberlein, Michael
Logun, Carolea
Shelhamer, James H.
TI Changes in microRNA and mRNA Expression with Differentiation of Human
Bronchial Epithelial Cells
SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
LA English
DT Article
DE airways epithelium; differentiation; microarrays; mucin 1; cell division
cycle homolog A
ID TRANSMEMBRANE CONDUCTANCE REGULATOR; AIR-LIQUID INTERFACE;
CYSTIC-FIBROSIS; MUCOCILIARY DIFFERENTIATION; MIR-17-92 CLUSTER; MUCIN
1; PROLIFERATION; TARGETS; CDC25A; PATHOGENESIS
AB We studied the changes in expression of microRNAs (miRNAs or miRs) and mRNA in normal human bronchial epithelial cells as they differentiate from an undifferentiated monolayer to a differentiated pseudostratified epithelium after 28 days of air-liquid interface (ALI) culture. After 28 days in ALI, the epithelial cells differentially expressed basal, ciliated, and goblet cell markers. Using Affymetrix microarrays, 20 human miRNAs were found to be up-regulated, whereas 35 miRNAs were found to be down-regulated in differentiated cells compared with undifferentiated cells. An analysis of changes in global mRNA expression revealed that 1,201 probe sets demonstrated an 8-fold change (FC) or greater at Day 28 of ALI culture. Of these, 816 were up-regulated and 385 were down-regulated. With differentiation, miR-449a increased (FC, 38.15), and was related to changes in mRNA for cell division cycle 25 homolog A (FC, 0.11). MiR-455 decreased (FC, 0.12) and was related to changes in mRNA for the epithelial cell marker, mucin 1 (FC, 136). Transfection with anti-miR-449 or miR-455-3p resulted in changes in target protein expression (cell division cycle 25 homolog A and mucin 1, respectively), whereas transfection with reporter genes with 3'-untranslated regions of these targets confirmed control of expression through that structure. Therefore, changes in specific miRNAs during human airway epithelial cell differentiation control gene and protein expression important for differentiation.
C1 [Martinez-Anton, Asuncion; Sokolowska, Milena; Kern, Steven; Alsaaty, Sara; Sun, Junfeng; Cai, Rongman; Danner, Robert L.; Eberlein, Michael; Logun, Carolea; Shelhamer, James H.] NIAID, Dept Crit Care Med, Ctr Clin, NIH, Bethesda, MD 20892 USA.
[Davis, A. Sally; Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Shelhamer, JH (reprint author), NIH, 9000 Rockville Pike,Bldg 10,Room 2C145, Bethesda, MD 20892 USA.
EM jshelhamer@cc.nih.gov
RI Cai, Rongman/C-5998-2015; Martinez Anton, Asuncion/A-5806-2017;
OI Cai, Rongman/0000-0003-2404-4852; Martinez Anton,
Asuncion/0000-0001-9758-5911; Davis, Anne/0000-0001-5711-3936
FU National Institutes of Health intramural research program
FX This work was supported by the National Institutes of Health intramural
research program.
NR 45
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U1 1
U2 10
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1044-1549
J9 AM J RESP CELL MOL
JI Am. J. Respir. Cell Mol. Biol.
PD SEP
PY 2013
VL 49
IS 3
BP 384
EP 395
DI 10.1165/rcmb.2012-0368OC
PG 12
WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
GA 215FQ
UT WOS:000324195400006
PM 23590309
ER
PT J
AU Zhou, J
Enewold, L
Zahm, SH
Jatoi, I
Shriver, C
Anderson, WF
Jeffery, DD
Andaya, A
Potter, JF
McGlynn, KA
Zhu, KM
AF Zhou, Jing
Enewold, Lindsey
Zahm, Shelia H.
Jatoi, Ismail
Shriver, Craig
Anderson, William F.
Jeffery, Diana D.
Andaya, Abegail
Potter, John F.
McGlynn, Katherine A.
Zhu, Kangmin
TI Breast conserving surgery versus mastectomy: the influence of
comorbidities on choice of surgical operation in the Department of
Defense health care system
SO AMERICAN JOURNAL OF SURGERY
LA English
DT Article
DE Breast cancer; Breast conserving surgery; Comorbidity; Department of
Defense health system; Mastectomy; Military
ID 20-YEAR FOLLOW-UP; CANCER PATIENTS; ADJUVANT CHEMOTHERAPY;
RANDOMIZED-TRIAL; OLDER WOMEN; POSTOPERATIVE RADIOTHERAPY;
RADIATION-THERAPY; LOCAL RECURRENCE; SURVIVAL; CARCINOMA
AB BACKGROUND: Studies on the effect of comorbidities on breast cancer operation have been limited and inconsistent. This study investigated whether pre-existing comorbidities influenced breast cancer surgical operation in an equal access health care system.
METHODS: This study was based on linked Department of Defense cancer registry and medical claims data. The study subjects were patients diagnosed with stage I to III breast cancer during 2001 to 2007. Logistic regression was used to determine if comorbidity was associated with operation type and time between diagnosis and operation.
RESULTS: Breast cancer patients with comorbidities were more likely to receive mastectomy (odds ratio [OR] = 1.27; 95% confidence interval [CI], 1.14 to 1.42) than breast conserving surgery plus radiation. Patients with comorbidities were also more likely to delay having operation than those without comorbidities (OR = 1.27; 95% CI, 1.14 to 1.41).
CONCLUSIONS: In an equal access health care system, comorbidity was associated with having a mastectomy and with a delay in undergoing operation. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Zhou, Jing; Shriver, Craig; Andaya, Abegail; Potter, John F.; Zhu, Kangmin] Walter Reed Natl Mil Med Ctr, John P Murtha Canc Ctr, Bethesda, MD USA.
[Enewold, Lindsey; Zahm, Shelia H.; Anderson, William F.; McGlynn, Katherine A.] NCI, NIH, Bethesda, MD 20892 USA.
[Jatoi, Ismail] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Shriver, Craig] Walter Reed Natl Mil Med Ctr, Gen Surg Serv, Bethesda, MD USA.
[Shriver, Craig; Potter, John F.; Zhu, Kangmin] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Jeffery, Diana D.] Tricare Management Act, Falls Church, VA USA.
RP Zhu, KM (reprint author), Walter Reed Natl Mil Med Ctr, John P Murtha Canc Ctr, Div Mil Epidemiol & Populat Sci, 11300 Rockville Pike,Suite 1215, Rockville, MD 20852 USA.
EM kangmin.zhu@usuhs.edu
RI Zahm, Shelia/B-5025-2015
FU John P. Murtha Cancer Center; Walter Reed National Military Medical
Center via the Uniformed Services University of the Health Sciences;
Henry M. Jackson Foundation for the Advancement of Military Medicine;
National Cancer Institute
FX This project was supported by John P. Murtha Cancer Center, Walter Reed
National Military Medical Center via the Uniformed Services University
of the Health Sciences under the auspices of the Henry M. Jackson
Foundation for the Advancement of Military Medicine and by the
intramural research program of the National Cancer Institute. The
original data linkage was supported by the former United States Military
Cancer Institute (USMCI) and Division of Cancer Epidemiology and
Genetics (DCEG), National Cancer Institute. The views expressed in this
article are those of the author and do not necessarily reflect the
official policy or position of the Department of the Navy, Army,
Department of Defense, National Cancer Institute, or the U. S.
Government. Nothing in the presentation implies any federal/DOD/DON
endorsement.
NR 41
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Z9 5
U1 0
U2 7
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9610
J9 AM J SURG
JI Am. J. Surg.
PD SEP
PY 2013
VL 206
IS 3
BP 393
EP 399
DI 10.1016/j.amjsurg.2013.01.034
PG 7
WC Surgery
SC Surgery
GA 213YK
UT WOS:000324096400017
PM 23866763
ER
PT J
AU Fung, KW
Kayaalp, M
Callaghan, F
McDonald, CJ
AF Fung, Kin Wah
Kayaalp, Mehmet
Callaghan, Fiona
McDonald, Clement J.
TI Comparison of Electronic Pharmacy Prescription Records With Manually
Collected Medication Histories in an Emergency Department
SO ANNALS OF EMERGENCY MEDICINE
LA English
DT Article
ID ADVERSE DRUG EVENTS; ADMISSION; DISCREPANCIES; VISITS
AB Study objective: Medication history is an essential part of patient assessment in emergency care. Patient-reported medication history can be incomplete. We study whether an electronic pharmacy-sourced prescription record can supplement the patient-reported history.
Methods: In a community hospital, we compared the patient-reported history obtained by triage nurses to a proprietary electronic pharmacy record in all emergency department (ED) patients during 3 months.
Results: Of 9,426 triaged patients, 5,001 (53%) had at least 1 (mean 7.7) prescription medication in the full-year electronic pharmacy record. Counting only recent prescription medications (supply lasting to at least 7 days before the ED visit), 3,688 patients (39%) had at least 1 (mean 4.0) recent medication. After adjustment for possible false-positive results, recent electronic prescription medication record enriched the patient-reported history by 28% (adding 1.1 drugs per patient). However, only 60% of patients with any active prescription medications from either source had any recent prescription medications in their electronic pharmacy record.
Conclusion: The electronic pharmacy prescription record augments the manually collected history.
C1 [Fung, Kin Wah; Kayaalp, Mehmet; Callaghan, Fiona; McDonald, Clement J.] NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bethesda, MD 20892 USA.
RP McDonald, CJ (reprint author), NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
EM clemmcdonald@mail.nih.gov
FU National Naval Medical Center; Intramural Research Program of the
National Institutes of Health, National Library of Medicine
FX By Annals policy, all authors are required to disclose any and all
commercial, financial, and other relationships in any way related to the
subject of this article as per ICMJE conflict of interest guidelines
(see www.icmje.org). The authors have stated that no such relationships
exist. This work was funded in part by the National Naval Medical Center
in support of the Bethesda Hospitals' Emergency Preparedness Partnership
and was supported by the Intramural Research Program of the National
Institutes of Health, National Library of Medicine.
NR 21
TC 2
Z9 3
U1 0
U2 4
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-0644
J9 ANN EMERG MED
JI Ann. Emerg. Med.
PD SEP
PY 2013
VL 62
IS 3
BP 205
EP 211
DI 10.1016/j.annemergmed.2013.04.014
PG 7
WC Emergency Medicine
SC Emergency Medicine
GA 218QS
UT WOS:000324448100004
PM 23688770
ER
PT J
AU Elagawany, M
Schmitt, M
Ghiaty, A
El-Etrawy, AS
Ibrahim, MA
Bihel, F
Sbardelotto, AB
Pessoa, C
Nguyen, TL
Hamel, E
Bourguignon, JJ
AF Elagawany, Mohamed
Schmitt, Martine
Ghiaty, Adel
El-Etrawy, A. Sh.
Ibrahim, Mohamed A.
Bihel, Frederic
Sbardelotto, Aline Borba
Pessoa, Claudia
Tam Luong Nguyen
Hamel, Ernest
Bourguignon, Jean Jacques
TI Synthesis and Antiproliferative Effects of 5,6-Disubstituted
Pyridazin-3(2H)-ones Designed as Conformationally Constrained
Combretastatin A-4 Analogues
SO ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
LA English
DT Article
DE Pyridazine; Combretastatin A-4; Cytotoxicity; Suzuki-Miyaura cross
coupling; Anticancer agent and Tubulin activity
ID CYTOTOXIC EVALUATION; TUBULIN; POTENT; AGENTS; POLYMERIZATION;
DERIVATIVES; INHIBITORS
AB Novel 5,6-disubstituted pyridazin-3(2H)-one derivatives were designed and synthesized as combretastatin A-4 analogues. Our objective was to overcome the spontaneous cis to trans isomerization of the compound. We therefore replaced the cis-double bond with a pyridazine ring. The antiproliferative activity of the novel analogues was evaluated against four human cancer cell lines (HL-60, MDA-MB-435, SF-295 and HCT-8). We found that the analogues had little activity either against selected cell lines or against purified tubulin. Molecular modeling studies may account for their inactivity.
C1 [Elagawany, Mohamed; Schmitt, Martine; Ibrahim, Mohamed A.; Bihel, Frederic; Bourguignon, Jean Jacques] Univ Strasbourg, Fac Pharm, Lab Innovat Therapeut, UMR 7200, F-67401 Illkirch Graffenstaden, France.
[Elagawany, Mohamed; El-Etrawy, A. Sh.; Ibrahim, Mohamed A.] Misr Univ Sci & Technol, Organ Chem Dept, Coll Pharm, Giza, Egypt.
[Ghiaty, Adel] Al Azhar Univ, Organ Chem Dept, Fac Pharm, Cairo 11884, Egypt.
[Sbardelotto, Aline Borba; Pessoa, Claudia] Univ Fed Ceara, Dept Fisiol & Farmacol, BR-60430270 Fortaleza, Ceara, Brazil.
[Tam Luong Nguyen] NIAID, Biodef Drug Dev Sect, Div Microbiol & Infect Dis, NIH, Bethesda, MD 20892 USA.
[Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program,NIH, Div Canc Treatment & Diag,Frederick Natl Lab Canc, Frederick, MD 21702 USA.
RP Elagawany, M (reprint author), Univ Strasbourg, Fac Pharm, Lab Innovat Therapeut, UMR 7200, 74 Route Rhin,BP 60024, F-67401 Illkirch Graffenstaden, France.
EM alfath_tours@yahoo.com; mschmitt@unistra.fr
RI Schmitt, Martine/B-5878-2016; BIHEL, Frederic/B-2895-2008
OI Schmitt, Martine/0000-0002-8723-9502; BIHEL,
Frederic/0000-0002-4122-0929
FU Intramural NIH HHS [Z99 CA999999]
NR 18
TC 1
Z9 1
U1 1
U2 13
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1871-5206
J9 ANTI-CANCER AGENT ME
JI Anti-Cancer Agents Med. Chem.
PD SEP
PY 2013
VL 13
IS 7
BP 1133
EP 1140
PG 8
WC Oncology; Chemistry, Medicinal
SC Oncology; Pharmacology & Pharmacy
GA 215ZG
UT WOS:000324249500018
PM 23574386
ER
PT J
AU Marfeo, EE
Haley, SM
Jette, AM
Eisen, SV
Ni, PS
Bogusz, K
Meterko, M
McDonough, CM
Chan, L
Brandt, DE
Rasch, EK
AF Marfeo, Elizabeth E.
Haley, Stephen M.
Jette, Alan M.
Eisen, Susan V.
Ni, Pengsheng
Bogusz, Kara
Meterko, Mark
McDonough, Christine M.
Chan, Leighton
Brandt, Diane E.
Rasch, Elizabeth K.
TI Conceptual Foundation for Measures of Physical Function and Behavioral
Health Function for Social Security Work Disability Evaluation
SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
LA English
DT Article
DE Concept formation; Disability evaluation; Disabled persons; Mental
health; Rehabilitation; Work disability
ID MENTAL-DISORDERS; INTERNATIONAL CLASSIFICATION; PERSONALITY; ICF;
PERFORMANCE; PERSPECTIVE; PREDICTORS; MODEL; REHABILITATION;
PARTICIPATION
AB Physical and mental impairments represent the 2 largest health condition categories for which workers receive Social Security disability benefits. Comprehensive assessment of physical and mental impairments should include aspects beyond medical conditions such as a person's underlying capabilities as well as activity demands relevant to the context of work. The objective of this article is to describe the initial conceptual stages of developing new measurement instruments of behavioral health and physical functioning relevant for Social Security work disability evaluation purposes. To outline a clear conceptualization of the constructs to be measured, 2 content models were developed using structured and informal qualitative approaches. We performed a structured literature review focusing on work disability and incorporating aspects of the International Classification of Functioning, Disability and Health as a unifying taxonomy for framework development. Expert interviews provided advice and consultation to enhance face validity of the resulting content models. The content model for work-related behavioral health function identifies 5 major domains: (1) behavior control, (2) basic interactions, (3) temperament and personality, (4) adaptability, and (5) workplace behaviors. The content model describing physical functioning includes 3 domains: (1) changing and maintaining body position, (2) whole-body mobility, and (3) carrying, moving, and handling objects. These content models informed subsequent measurement properties including item development and measurement scale construction, and provided conceptual coherence guiding future empirical inquiry. The proposed measurement approaches show promise to comprehensively and systematically assess physical and behavioral health functioning relevant to work. (C) 2013 by the American Congress of Rehabilitation Medicine
C1 [Marfeo, Elizabeth E.; Haley, Stephen M.; Jette, Alan M.; Ni, Pengsheng; Bogusz, Kara; McDonough, Christine M.] Boston Univ, Sch Publ Hlth, Hlth & Disabil Res Inst, Boston, MA 02118 USA.
[Eisen, Susan V.] Edith Nourse Rogers Mem Vet Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA.
[Eisen, Susan V.; Meterko, Mark] Boston Univ, Sch Publ Hlth, Hlth Policy & Management Dept, Boston, MA 02118 USA.
[McDonough, Christine M.] Geisel Sch Med, Dartmouth Inst Hlth Policy & Clin Practice, Lebanon, NH USA.
[Chan, Leighton; Brandt, Diane E.; Rasch, Elizabeth K.] NIH, Dept Rehabil Med, Mark O Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
RP Marfeo, EE (reprint author), Boston Univ, Sch Publ Hlth, Hlth & Disabil Res Inst, 715 Albany St,T5W, Boston, MA 02118 USA.
EM emarfeo@bu.edu
FU Social Security Administration and National Institutes of Health
(SSA-NIH) Interagency Agreements (NIH) [HHSN269200900004C,
HHSN269201000011C, HHSN269201100009I]; NIH
FX Supported by Social Security Administration and National Institutes of
Health (SSA-NIH) Interagency Agreements (NIH contract nos.
HHSN269200900004C, HHSN269201000011C, HHSN269201100009I) and by the NIH
intramural research program.
NR 62
TC 10
Z9 10
U1 3
U2 21
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0003-9993
J9 ARCH PHYS MED REHAB
JI Arch. Phys. Med. Rehabil.
PD SEP
PY 2013
VL 94
IS 9
BP 1645
EP 1652
DI 10.1016/j.apmr.2013.03.015
PG 8
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 214QZ
UT WOS:000324151900001
PM 23548543
ER
PT J
AU McDonough, CM
Jette, AM
Ni, PS
Bogusz, K
Marfeo, EE
Brandt, DE
Chan, L
Meterko, M
Haley, SM
Rasch, EK
AF McDonough, Christine M.
Jette, Alan M.
Ni, Pengsheng
Bogusz, Kara
Marfeo, Elizabeth E.
Brandt, Diane E.
Chan, Leighton
Meterko, Mark
Haley, Stephen M.
Rasch, Elizabeth K.
TI Development of a Self-Report Physical Function Instrument for Disability
Assessment: Item Pool Construction and Factor Analysis
SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
LA English
DT Article; Proceedings Paper
CT Meeting of the International-Association-of-Bodily-Impairment
CY SEP 12, 2012
CL Montreal, CANADA
SP Int Assoc Bodily Impairment
DE Disability evaluation; Disabled persons; Factor analysis, statistical;
Insurance; Questionnaires; Rehabilitation
ID INFORMATION-SYSTEM PROMIS; FIT INDEXES; OUTCOMES MEASUREMENT; CRITERIA;
MODELS; BANKS
AB Objectives: To build a comprehensive item pool representing work-relevant physical functioning and to test the factor structure of the item pool. These developmental steps represent initial outcomes of a broader project to develop instruments for the assessment of function within the context of Social Security Administration (SSA) disability programs.
Design: Comprehensive literature review; gap analysis; item generation with expert panel input; stakeholder interviews; cognitive interviews; cross-sectional survey administration; and exploratory and confirmatory factor analyses to assess item pool structure.
Setting: In-person and semistructured interviews and Internet and telephone surveys.
Participants: Sample of SSA claimants (n=1017) and a normative sample of adults from the U.S. general population (n=999).
Interventions: Not applicable.
Main Outcome Measure: Model fit statistics.
Results: The final item pool consisted of 139 items. Within the claimant sample, 58.7% were white; 31.8% were black; 46.6% were women; and the mean age was 49.7 years. Initial factor analyses revealed a 4-factor solution, which included more items and allowed separate characterization of: (1) changing and maintaining body position, (2) whole body mobility, (3) upper body function, and (4) upper extremity fine motor. The final 4-factor model included 91 items. Confirmatory factor analyses for the 4-factor models for the claimant and the normative samples demonstrated very good fit. Fit statistics for claimant and normative samples, respectively, were: Comparative Fit Index=.93 and .98; Tucker-Lewis Index =.92 and .98; and root mean square error approximation=.05 and .04.
Conclusions: The factor structure of the physical function item pool closely resembled the hypothesized content model. The 4 scales relevant to work activities offer promise for providing reliable information about claimant physical functioning relevant to work disability. (C) 2013 by the American Congress of Rehabilitation Medicine
C1 [McDonough, Christine M.; Jette, Alan M.; Ni, Pengsheng; Bogusz, Kara; Marfeo, Elizabeth E.; Meterko, Mark] Boston Univ, Sch Publ Hlth, Hlth & Disabil Res Inst, Dept Hlth Policy & Management, Boston, MA 02118 USA.
[McDonough, Christine M.] Geiset Sch Med, Dartmouth Inst Hlth Policy & Clin Practice, Lebanon, NH USA.
[Brandt, Diane E.; Chan, Leighton; Rasch, Elizabeth K.] NIH, Dept Rehabil Med, Clin Res Ctr, Bethesda, MD 20892 USA.
RP McDonough, CM (reprint author), Boston Univ, Sch Publ Hlth, Hlth & Disabil Res Inst, 715 Albany St T5W, Boston, MA 02118 USA.
EM cmm@bu.edu
OI Jette, Alan/0000-0002-2117-9973; Ni, Pengsheng/0000-0003-1774-2185;
McDonough, Christine/0000-0002-4493-8610; Marfeo,
Elizabeth/0000-0003-3848-6918
FU CLC NIH HHS [HHSN269200900004C, HHSN269200900004I, HHSN269201000011C,
HHSN269201100009I]; Intramural NIH HHS [ZIA CL060065-06]; NIAMS NIH HHS
[P60 AR062799]; PHS HHS [HHSN269200900004C, HHSN269201000011C,
HHSN269201100009I]
NR 37
TC 10
Z9 12
U1 2
U2 24
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0003-9993
J9 ARCH PHYS MED REHAB
JI Arch. Phys. Med. Rehabil.
PD SEP
PY 2013
VL 94
IS 9
BP 1653
EP 1660
DI 10.1016/j.apmr.2013.03.011
PG 8
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 214QZ
UT WOS:000324151900002
PM 23542402
ER
PT J
AU Ni, PS
McDonough, CM
Jette, AM
Bogusz, K
Marfeo, EE
Rasch, EK
Brandt, DE
Meterko, M
Haley, SM
Chan, L
AF Ni, Pengsheng
McDonough, Christine M.
Jette, Alan M.
Bogusz, Kara
Marfeo, Elizabeth E.
Rasch, Elizabeth K.
Brandt, Diane E.
Meterko, Mark
Haley, Stephen M.
Chan, Leighton
TI Development of a Computer-Adaptive Physical Function Instrument for
Social Security Administration Disability Determination
SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
LA English
DT Article; Proceedings Paper
CT Meeting of the International-Association-of-Bodily-Impairment
CY SEP 12, 2012
CL Montreal, CANADA
SP Int Assoc Bodily Impairment
DE Disability evaluation; Disabled persons; Health Status Indicators;
Insurance; Psychometrics; Questionnaires; Rehabilitation; Statistical
model
ID ITEM RESPONSE THEORY; INFORMATION-SYSTEM PROMIS; FIT INDEX; OUTCOMES;
EFFICIENCY; BANK; REHABILITATION; PERFORMANCE; MODELS; S-X-2
AB Objectives: To develop and test an instrument to assess physical function for Social Security Administration (SSA) disability programs, the SSA-Physical Function (SSA-PF) instrument. Item response theory (IRT) analyses were used to (1) create a calibrated item bank for each of the factors identified in prior factor analyses, (2) assess the fit of the items within each scale, (3) develop separate computer-adaptive testing (CAT) instruments for each scale, and (4) conduct initial psychometric testing.
Design: Cross-sectional data collection; IRT analyses; CAT simulation.
Setting: Telephone and Internet survey.
Participants: Two samples: SSA claimants (n=1017) and adults from the U.S. general population (n=999).
Interventions: None.
Main Outcome Measures: Model fit statistics, correlation, and reliability coefficients.
Results: IRT analyses resulted in 5 unidimensional SSA-PF scales: Changing & Maintaining Body Position, Whole Body Mobility, Upper Body Function, Upper Extremity Fine Motor, and Wheelchair Mobility for a total of 102 items. High CAT accuracy was demonstrated by strong correlations between simulated CAT scores and those from the full item banks. On comparing the simulated CATs with the full item banks, very little loss of reliability or precision was noted, except at the lower and upper ranges of each scale. No difference in response patterns by age or sex was noted. The distributions of claimant scores were shifted to the lower end of each scale compared with those of a sample of U.S. adults.
Conclusions: The SSA-PF instrument contributes important new methodology for measuring the physical function of adults applying to the SSA disability programs. Initial evaluation revealed that the SSA-PF instrument achieved considerable breadth of coverage in each content domain and demonstrated noteworthy psychometric properties. (C) 2013 by the American Congress of Rehabilitation Medicine
C1 [Ni, Pengsheng; McDonough, Christine M.; Jette, Alan M.; Bogusz, Kara; Marfeo, Elizabeth E.; Meterko, Mark] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Hlth & Disabil Res Inst, Boston, MA USA.
[McDonough, Christine M.] Geisel Sch Med, Dartmouth Inst Hlth Policy & Clin Practice, Lebanon, NH USA.
[Rasch, Elizabeth K.; Brandt, Diane E.; Chan, Leighton] NIH, Dept Rehabil Med, Clin Res Ctr, Bethesda, MD 20892 USA.
RP Ni, PS (reprint author), Hlth & Disabil Res Inst, 715 Albany St T5W, Boston, MA 02118 USA.
EM psni@bu.edu
OI Jette, Alan/0000-0002-2117-9973; Ni, Pengsheng/0000-0003-1774-2185;
Marfeo, Elizabeth/0000-0003-3848-6918; McDonough,
Christine/0000-0002-4493-8610
FU CLC NIH HHS [HHSN269200900004C, HHSN269200900004I, HHSN269201000011C,
HHSN269201100009I]; Intramural NIH HHS [ZIA CL060065-06]; NIAMS NIH HHS
[P60 AR062799]; PHS HHS [HHSN269200900004C, HHSN269201000011C,
HHSN269201100009I]
NR 33
TC 10
Z9 10
U1 0
U2 14
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0003-9993
J9 ARCH PHYS MED REHAB
JI Arch. Phys. Med. Rehabil.
PD SEP
PY 2013
VL 94
IS 9
BP 1661
EP 1669
DI 10.1016/j.apmr.2013.03.021
PG 9
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 214QZ
UT WOS:000324151900003
PM 23578594
ER
PT J
AU Marfeo, EE
Ni, PS
Haley, SM
Jette, AM
Bogusz, K
Meterko, M
McDonough, CM
Chan, L
Brandt, DE
Rasch, EK
AF Marfeo, Elizabeth E.
Ni, Pengsheng
Haley, Stephen M.
Jette, Alan M.
Bogusz, Kara
Meterko, Mark
McDonough, Christine M.
Chan, Leighton
Brandt, Diane E.
Rasch, Elizabeth K.
TI Development of an Instrument to Measure Behavioral Health Function for
Work Disability: Item Pool Construction and Factor Analysis
SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
LA English
DT Article
DE Disability evaluation; Mental health; Outcome assessment (health care);
Psychometrics; Rehabilitation
ID QUALITY-OF-LIFE; INFORMATION-SYSTEM PROMIS; PSYCHIATRIC DISABILITIES;
MENTAL-HEALTH; INDIVIDUALS; NEUROLOGY; PEOPLE; MODEL; BANKS; ICF
AB Objectives: To develop a broad set of claimant-reported items to assess behavioral health functioning relevant to the Social Security disability determination processes, and to evaluate the underlying structure of behavioral health functioning for use in development of a new functional assessment instrument.
Design: Cross-sectional.
Setting: Community.
Participants: Item pools of behavioral health functioning were developed, refined, and field tested in a sample of persons applying for Social Security disability benefits (N=1015) who reported difficulties working because of mental or both mental and physical conditions.
Interventions: None.
Main Outcome Measure: Social Security Administration Behavioral Health (SSA-BH) measurement instrument.
Results: Confirmatory factor analysis (CFA) specified that a 4-factor model (self-efficacy, mood and emotions, behavioral control, social interactions) had the optimal fit with the data and was also consistent with our hypothesized conceptual framework for characterizing behavioral health functioning. When the items within each of the 4 scales were tested in CFA, the fit statistics indicated adequate support for characterizing behavioral health as a unidimensional construct along these 4 distinct scales of function.
Conclusions: This work represents a significant advance both conceptually and psychometrically in assessment methodologies for work-related behavioral health. The measurement of behavioral health functioning relevant to the context of work requires the assessment of multiple dimensions of behavioral health functioning. Specifically, we identified a 4-factor model solution that represented key domains of work-related behavioral health functioning. These results guided the development and scale formation of a new SSA-BH instrument. (C) 2013 by the American Congress of Rehabilitation Medicine
C1 [Marfeo, Elizabeth E.; Ni, Pengsheng; Haley, Stephen M.; Jette, Alan M.; Bogusz, Kara; Meterko, Mark; McDonough, Christine M.] Boston Univ, Sch Publ Hlth, Hlth & Disabil Res Inst, Boston, MA 02118 USA.
[Chan, Leighton; Brandt, Diane E.; Rasch, Elizabeth K.] NIH, Dept Rehabil Med, Mark O Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
[McDonough, Christine M.] Geisel Sch Med, Dartmouth Inst Hlth Policy & Clin Practice, Lebanon, NH USA.
RP Marfeo, EE (reprint author), Boston Univ, Sch Publ Hlth, Hlth & Disabil Res Inst, 715 Albany St,T5W, Boston, MA 02118 USA.
EM emarfeo@bu.edu
OI Marfeo, Elizabeth/0000-0003-3848-6918
FU SSA-NIH [HHSN269200900004C, HHSN269201000011C, HHSN269201100009I]; NIH
FX Supported by SSA-NIH Interagency Agreements (NIH contract nos.
HHSN269200900004C, HHSN269201000011C, HHSN269201100009I) and by the NIH
intramural research program.
NR 36
TC 8
Z9 8
U1 2
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 0003-9993
J9 ARCH PHYS MED REHAB
JI Arch. Phys. Med. Rehabil.
PD SEP
PY 2013
VL 94
IS 9
BP 1670
EP 1678
DI 10.1016/j.apmr.2013.03.013
PG 9
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 214QZ
UT WOS:000324151900004
PM 23548542
ER
PT J
AU Marfeo, EE
Ni, PS
Haley, SM
Bogusz, K
Meterko, M
McDonough, CM
Chan, L
Rasch, EK
Brandt, DE
Jette, AM
AF Marfeo, Elizabeth E.
Ni, Pengsheng
Haley, Stephen M.
Bogusz, Kara
Meterko, Mark
McDonough, Christine M.
Chan, Leighton
Rasch, Elizabeth K.
Brandt, Diane E.
Jette, Alan M.
TI Scale Refinement and Initial Evaluation of a Behavioral Health Function
Measurement Tool for Work Disability Evaluation
SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
LA English
DT Article
DE Disability evaluation; Outcome assessment (health care); Rehabilitation;
United States Social Security Administration
ID ITEM RESPONSE THEORY; FIT INDEX; PERFORMANCE; RELIABILITY; MODELS;
S-X-2; PAC
AB Objective: To use item response theory (IRT) data simulations to construct and perform initial psychometric testing of a newly developed instrument, the Social Security Administration Behavioral Health Function (SSA-BH) instrument, that aims to assess behavioral health functioning relevant to the context of work.
Design: Cross-sectional survey followed by IRT calibration data simulations.
Setting: Community.
Participants: Sample of individuals applying for Social Security Administration disability benefits: claimants (n=1015) and a normative comparative sample of U.S. adults (n=1000).
Interventions: None.
Main Outcome Measure: SSA-BH measurement instrument.
Results: IRT analyses supported the unidimensionality of 4 SSA-BH scales: mood and emotions (35 items), self-efficacy (23 items), social interactions (6 items), and behavioral control (15 items). All SSA-BH scales demonstrated strong psychometric properties including reliability, accuracy, and breadth of coverage. High correlations of the simulated 5- or 10-item computer adaptive tests with the full item bank indicated robust ability of the computer adaptive testing approach to comprehensively characterize behavioral health function along 4 distinct dimensions.
Conclusions: Initial testing and evaluation of the SSA-BH instrument demonstrated good accuracy, reliability, and content coverage along all 4 scales. Behavioral function profiles of Social Security Administration claimants were generated and compared with age- and sex-matched norms along 4 scales: mood and emotions, behavioral control, social interactions, and self-efficacy. Using the computer adaptive test-based approach offers the ability to collect standardized, comprehensive functional information about claimants in an efficient way, which may prove useful in the context of the Social Security Administration's work disability programs. (C) 2013 by the American Congress of Rehabilitation Medicine
C1 [Marfeo, Elizabeth E.; Ni, Pengsheng; Haley, Stephen M.; Bogusz, Kara; Meterko, Mark; McDonough, Christine M.; Jette, Alan M.] Boston Univ, Sch Publ Hlth, Hlth & Disabil Res Inst, Boston, MA 02118 USA.
[McDonough, Christine M.] Geisel Sch Med, Dartmouth Inst Hlth Policy & Clin Practice, Lebanon, NH USA.
[Chan, Leighton; Rasch, Elizabeth K.; Brandt, Diane E.] NIH, Dept Rehabil Med, Mark O Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
RP Marfeo, EE (reprint author), Boston Univ, Sch Publ Hlth, Hlth & Disabil Res Inst, 715 Albany St,T5W, Boston, MA 02118 USA.
EM emarfeo@bu.edu
OI Jette, Alan/0000-0002-2117-9973; Ni, Pengsheng/0000-0003-1774-2185;
McDonough, Christine/0000-0002-4493-8610; Marfeo,
Elizabeth/0000-0003-3848-6918
FU Social Security Administration and the National Institutes of Health
Interagency Agreements (National Institutes of Health)
[HHSN269200900004C, HHSN269201000 011C, HHSN269201100009I]; National
Institutes of Health
FX Supported by Social Security Administration and the National Institutes
of Health Interagency Agreements (National Institutes of Health contract
nos. HHSN269200900004C, HHSN269201000 011C, and HHSN269201100009I); and
the National Institutes of Health Intramural Research Program.
NR 33
TC 8
Z9 8
U1 2
U2 11
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0003-9993
J9 ARCH PHYS MED REHAB
JI Arch. Phys. Med. Rehabil.
PD SEP
PY 2013
VL 94
IS 9
BP 1679
EP 1686
DI 10.1016/j.apmr.2013.03.012
PG 8
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 214QZ
UT WOS:000324151900005
PM 23542404
ER
PT J
AU McIver, ZA
Yin, F
Hughes, T
Battiwalla, M
Ito, S
Koklanaris, E
Haggerty, J
Barrett, AJ
AF McIver, Z. A.
Yin, F.
Hughes, T.
Battiwalla, M.
Ito, S.
Koklanaris, E.
Haggerty, J.
Barrett, A. John
TI Second hematopoietic SCT for leukemia relapsing after myeloablative T
cell-depleted transplants does not prolong survival
SO BONE MARROW TRANSPLANTATION
LA English
DT Article
DE second SCT; leukemia; relapse; T-depleted; survival
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; OUTCOMES; AML; MALIGNANCIES; MDS
AB Patients with leukemia relapsing after allogeneic hematopoietic SCT have a dismal prognosis. A second SCT offers a further opportunity for cure, but has a high rate of treatment failure. To determine the utility of this option, we analyzed 59 consecutive patients relapsing after a myeloablative HLA-matched sibling T cell-depleted (TCD) SCT. Twenty-five patients (13 relapsing within 6 months and 12 relapsing between 6 and 170 months after the first SCT) received a T-replete second SCT. Thirty-eight patients relapsing early had a shorter survival than the 21 patients relapsing later (median 96 vs 298 days, P = 0.0002). In patients relapsing early, the second SCT did not improve OS compared with patients receiving non-SCT treatments (median survival 109 vs 80 days, P = 0.41). In patients relapsing late, despite an early trend in favor of second SCT, survival was comparable for patients receiving a second SCT compared with non retransplanted patients (median survival 363.5 vs 162 days, P = 0.49). Disappointingly, our results do not demonstrate an important survival benefit for a second T-replete allogeneic SCT to treat relapse following a TCD SCT.
C1 [McIver, Z. A.; Yin, F.; Hughes, T.; Battiwalla, M.; Ito, S.; Koklanaris, E.; Haggerty, J.; Barrett, A. John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP McIver, ZA (reprint author), NHLBI, Hematol Branch, NIH, 10 Ctr Dr,Blg 10-CRC Rm 3-5320, Bethesda, MD 20892 USA.
EM zmciver@tulane.edu; fang.yin@nih.gov
FU National Heart, Lung, and Blood Institute
FX The study was sponsored by the National Heart, Lung, and Blood
Institute, and registered as ClinicalTrials.gov-registered trials
NCT00001623, NCT00001873, NCT00353860, NCT00066300, NCT00079391,
NCT00398346 and NCT00467961.
NR 20
TC 5
Z9 5
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD SEP
PY 2013
VL 48
IS 9
BP 1192
EP 1197
DI 10.1038/bmt.2013.39
PG 6
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA 214VX
UT WOS:000324166300008
PM 23524640
ER
PT J
AU Alavanja, MCR
Ross, MK
Bonner, MR
AF Alavanja, Michael C. R.
Ross, Matthew K.
Bonner, Matthew R.
TI Reply to Increased cancer burden among pesticide applicators and others
due to pesticide exposure
SO CA-A CANCER JOURNAL FOR CLINICIANS
LA English
DT Letter
C1 [Alavanja, Michael C. R.] NCI, Div Canc Epidemiol & Genet, North Bethesda, MD USA.
[Ross, Matthew K.] Mississippi State Univ, Coll Vet Med, Dept Basic Sci, Ctr Environm Hlth Sci, Mississippi State, MS 39762 USA.
[Bonner, Matthew R.] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
RP Alavanja, MCR (reprint author), NCI, Div Canc Epidemiol & Genet, North Bethesda, MD USA.
FU Intramural NIH HHS [ZIA CP010119-17]
NR 5
TC 3
Z9 3
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-9235
J9 CA-CANCER J CLIN
JI CA-Cancer J. Clin.
PD SEP
PY 2013
VL 63
IS 5
BP 366
EP 367
DI 10.3322/caac.21193
PG 2
WC Oncology
SC Oncology
GA 213BT
UT WOS:000324029100007
PM 23722636
ER
PT J
AU Stamatakis, L
Siddiqui, MM
Nix, JW
Logan, J
Rais-Bahrami, S
Walton-Diaz, A
Hoang, AN
Vourganti, S
Truong, H
Shuch, B
Parnes, HL
Turkbey, B
Choyke, PL
Wood, BJ
Simon, RM
Pinto, PA
AF Stamatakis, Lambros
Siddiqui, M. Minhaj
Nix, Jeffrey W.
Logan, Jennifer
Rais-Bahrami, Soroush
Walton-Diaz, Annerleim
Hoang, Anthony N.
Vourganti, Srinivas
Hong Truong
Shuch, Brian
Parnes, Howard L.
Turkbey, Baris
Choyke, Peter L.
Wood, Bradford J.
Simon, Richard M.
Pinto, Peter A.
TI Accuracy of multiparametric magnetic resonance imaging in confirming
eligibility for active surveillance for men with prostate cancer
SO CANCER
LA English
DT Article
DE prostate neoplasms; active surveillance; magnetic resonance imaging;
early detection of cancer
ID TUMOR VOLUME; BIOPSY; MANAGEMENT; FUSION; MRI; PREDICTION; EXPERIENCE;
UPDATE; TRUS
AB BACKGROUND Active surveillance (AS) is an attempt to avoid overtreatment of clinically insignificant prostate cancer (PCa); however, patient selection remains controversial. Multiparametric prostate magnetic resonance imaging (MP-MRI) may help better select AS candidates.
METHODS We reviewed a cohort of men who underwent MP-MRI with MRI/Ultrasound fusion-guided prostate biopsy and selected potential AS patients at entry using Johns Hopkins criteria. MP-MRI findings were assessed, including number of lesions, dominant lesion diameter, total lesion volume, prostate volume, and lesion density (calculated as total lesion volume/prostate volume). Lesions were assigned a suspicion score for cancer by MRI. AS criteria were reapplied based on the confirmatory biopsy, and accuracy of MP-MRI in predicting AS candidacy was assessed. Logistic regression modeling and chi-square statistics were used to assess associations between MP-MRI interpretation and biopsy results.
RESULTS Eighty-five patients qualified for AS with a mean age of 60.2 years and mean prostate-specific antigen level of 4.8 ng/mL. Of these, 25 patients (29%) were reclassified as not meeting AS criteria based on confirmatory biopsy. Number of lesions, lesion density, and highest MRI lesion suspicion were significantly associated with confirmatory biopsy AS reclassification. These MRI-based factors were combined to create a nomogram that generates a probability for confirmed AS candidacy.
CONCLUSION As clinicians counsel patients with PCa, MP-MRI may contribute to the decision-making process when considering AS. Three MRI-based factors (number of lesions, lesion suspicion, and lesion density) were associated with confirmatory biopsy outcome and reclassification. A nomogram using these factors has promising predictive accuracy for which future validation is necessary. Cancer 2013;119:3359-66. Published 2013. This article is a U.S. Government work and is in the public domain in the USA
C1 [Stamatakis, Lambros; Siddiqui, M. Minhaj; Nix, Jeffrey W.; Logan, Jennifer; Rais-Bahrami, Soroush; Walton-Diaz, Annerleim; Hoang, Anthony N.; Vourganti, Srinivas; Hong Truong; Shuch, Brian; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Parnes, Howard L.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Turkbey, Baris; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
[Wood, Bradford J.; Pinto, Peter A.] NCI, Ctr Intervent Oncol, Bethesda, MD 20892 USA.
[Wood, Bradford J.; Pinto, Peter A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Simon, Richard M.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
RP Pinto, PA (reprint author), NCI, Urol Oncol Branch, NIH, 10 Ctr Dr,MSC 1210,Bldg 10 CRC Room 2W-5940, Bethesda, MD 20892 USA.
EM pintop@mail.nih.gov
OI Siddiqui, Mohummad/0000-0002-4484-6820; Rais-Bahrami,
Soroush/0000-0001-9466-9925
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX This study was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 29
TC 90
Z9 90
U1 1
U2 5
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 SEP
PY 2013
VL 119
IS 18
BP 3359
EP 3366
DI 10.1002/cncr.28216
PG 8
WC Oncology
SC Oncology
GA 211EN
UT WOS:000323887900017
PM 23821585
ER
PT J
AU Dowling, EC
Chawla, N
Forsythe, LP
de Moor, J
McNeel, T
Rozjabek, HM
Ekwueme, DU
Yabroff, KR
AF Dowling, Emily C.
Chawla, Neetu
Forsythe, Laura P.
de Moor, Janet
McNeel, Timothy
Rozjabek, Heather M.
Ekwueme, Donatus U.
Yabroff, K. Robin
TI Lost productivity and burden of illness in cancer survivors with and
without other chronic conditions
SO CANCER
LA English
DT Article
DE MEPS; quality of life; cancer survivors; chronic conditions;
comorbidities
ID MENTAL-HEALTH STATUS; QUALITY-OF-LIFE; CARE; LIMITATIONS; RECORDS; AGE
AB BACKGROUND Cancer survivors may experience long-term and late effects from treatment that adversely affect health and limit functioning. Few studies examine lost productivity and disease burden in cancer survivors compared with individuals who have other chronic conditions or by cancer type.
METHODS We identified 4960 cancer survivors and 64,431 other individuals from the 2008-2010 Medical Expenditure Panel Survey and compared multiple measures of disease burden, including health status and lost productivity, between conditions and by cancer site for cancer survivors. All analyses controlled for the effects of age, sex, race/ethnicity, and number of comorbid conditions.
RESULTS Overall, in adjusted analyses in multiple models, cancer survivors with another chronic disease (heart disease or diabetes) experienced higher levels of burden compared with individuals with a history of cancer only, chronic disease only, and neither cancer, heart disease, nor diabetes across multiple measures (P<.05). Among cancer survivors, individuals with short survival cancers and multiple cancers consistently had the highest levels of burden across multiple measures (P<.0001).
CONCLUSIONS Cancer survivors who have another chronic disease experience more limitations and higher levels of burden across multiple measures. Limitations are particularly severe in cancer survivors with short survival cancer and multiple cancers. Cancer 2013;119:3393-401. (c) 2013 American Cancer Society.
C1 [Dowling, Emily C.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA.
[Chawla, Neetu; Forsythe, Laura P.; de Moor, Janet; Rozjabek, Heather M.; Yabroff, K. Robin] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[McNeel, Timothy] Informat Management Serv Inc, Rockville, MD USA.
[Ekwueme, Donatus U.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA.
RP Dowling, EC (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA.
EM edowling@mgh-ita.org
OI Yabroff, K. Robin/0000-0003-0644-5572
NR 27
TC 14
Z9 14
U1 2
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 SEP
PY 2013
VL 119
IS 18
BP 3393
EP 3401
DI 10.1002/cncr.28214
PG 9
WC Oncology
SC Oncology
GA 211EN
UT WOS:000323887900021
PM 23794146
ER
PT J
AU Witherspoon, M
Chen, QY
Kopelovich, L
Gross, SS
Lipkin, SM
AF Witherspoon, Mavee
Chen, Qiuying
Kopelovich, Levy
Gross, Steven S.
Lipkin, Steven M.
TI Unbiased Metabolite Profiling Indicates That a Diminished Thymidine Pool
Is the Underlying Mechanism of Colon Cancer Chemoprevention by
Alpha-Difluoromethylornithine
SO CANCER DISCOVERY
LA English
DT Article
ID DEOXYRIBONUCLEOSIDE TRIPHOSPHATE POOLS; S-ADENOSYLMETHIONINE
DECARBOXYLASE; METHYLENETETRAHYDROFOLATE REDUCTASE; POLYAMINE
METABOLISM; CELLS; INHIBITION; PREVENTION; MOUSE; TRIAL; CARCINOGENESIS
AB The ornithine decarboxylase inhibitor alpha-difluoromethylornithine (DFMO) is a highly effective chemopreventive agent for colorectal cancer thought to act via polyamine depletion. However, in DFMO-treated patients, mucosal polyamine levels do not directly correlate with colorectal cancer risk. Untargeted metabolite profiling was used to broadly survey DFMO actions on colon cancer cell metabolism. We found that DFMO treatment of Apc(Min) intestinal tumors and human colorectal cancer cells is associated with reduced levels of folate-dependent metabolites, including S-adenosylmethionine (SAM), thymidine pools, and related pathway intermediates. We hypothesized that unrestrained SAM consumption/regeneration constitutes a futile DFMO-triggered cascade that can steal tetrahydrofolate from thymidylate synthase and thereby diminish thymidine pools. In accord with this hypothesis, DFMO treatment altered the folate cofactor balance and thymidine supplementation prevented DFMO-elicited cytostasis without restoring polyamine levels. These findings suggest that thymidine metabolite pool insufficiency is a fundamental mechanism of DFMO cytostatic activity.
SIGNIFICANCE: A previously unappreciated metabolic linkage between polyamine and thymidine biosynthesis is revealed, based on the competing requirement of these pathways for a limited pool of tetrahydrofolate cofactor. This study identifies the first shared mechanism for colorectal cancer chemoprevention and chemotherapy, suggesting a common metabolic target for both premalignant and malignant colon cells. (C) 2013 AACR.
C1 [Witherspoon, Mavee; Lipkin, Steven M.] Weill Cornell Med Coll, Dept Med Genet Med & Cell Biol, New York, NY 10021 USA.
[Chen, Qiuying; Gross, Steven S.] Weill Cornell Med Coll, Dept Pharmacol, New York, NY 10021 USA.
[Kopelovich, Levy] NCI, Div Chemoprevent, Frederick, MD 21701 USA.
RP Lipkin, SM (reprint author), Weill Cornell Med Coll, Room 718 HSS,101 City Dr, New York, NY 10021 USA.
EM ssgross@med.cornell.edu; stl2012@med.cornell.edu
FU NCI [NO1-CN 43302]; NHLBI [R37 HL87062]
FX This research was supported by NCI NO1-CN 43302 (to S. M. Lipkin), NHLBI
grant R37 HL87062 (to S. S. Gross), and gifts from the Agilent
Foundation and Matthew Bell.
NR 41
TC 16
Z9 16
U1 0
U2 10
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 2159-8274
J9 CANCER DISCOV
JI Cancer Discov.
PD SEP
PY 2013
VL 3
IS 9
BP 1072
EP 1081
DI 10.1158/2159-8290.CD-12-0305
PG 10
WC Oncology
SC Oncology
GA 215YH
UT WOS:000324246600026
PM 23771434
ER
PT J
AU Subbaramaiah, K
Sue, E
Bhardwaj, P
Du, BH
Hudis, CA
Giri, D
Kopelovich, L
Zhou, XK
Dannenberg, AJ
AF Subbaramaiah, Kotha
Sue, Erika
Bhardwaj, Priya
Du, Baoheng
Hudis, Clifford A.
Giri, Dilip
Kopelovich, Levy
Zhou, Xi Kathy
Dannenberg, Andrew J.
TI Dietary Polyphenols Suppress Elevated Levels of Proinflammatory
Mediators and Aromatase in the Mammary Gland of Obese Mice
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID NF-KAPPA-B; INDUCED INSULIN-RESISTANCE; BODY-MASS INDEX; BREAST-CANCER;
POSTMENOPAUSAL WOMEN; PROSTATE-CANCER; ANDROGEN RECEPTOR;
KINASE-ACTIVITY; ADIPOSE-TISSUE; EXPRESSION
AB In postmenopausal women, obesity is a risk factor for the development of hormone receptor-positive breast cancer driven by estrogen. After menopause, aromatization of androgen precursors in adipose tissue is a major synthetic source of estrogen. Recently, in mouse models and women, we identified an obesity-inflammation-aromatase axis. This obesity-induced inflammation is characterized by crown-like structures (CLS) consisting of dead adipocytes encircled by macrophages in breast white adipose tissue. CLS occur in association with NF-kappa B activation, elevated levels of proinflammatory mediators, and increased aromatase expression. Saturated fatty acids released from adipocytes have been linked to obesity-related white adipose tissue inflammation. Here we found that stearic acid, a prototypic saturated fatty acid, stimulated Akt-dependent activation of NF-kappa B resulting in increased levels of proinflammatory mediators [TNF-alpha, interleukin (IL)-1 beta, COX-2] in macrophages leading, in turn, to the induction of aromatase. Several polyphenols (resveratrol, curcumin, epigallocatechin gallate) blocked these inductive effects of stearic acid. Zyflamend, a widely used polyherbal preparation that contains numerous polyphenols, possessed similar suppressive effects. In a mouse model of obesity, treatment with Zyflamend suppressed levels of phospho-Akt, NF-kappa B binding activity, proinflammatory mediators, and aromatase in the mammary gland. Collectively, these results suggest that targeting the activation of NF-kappa B is a promising approach for reducing levels of proinflammatory mediators and aromatase in inflamed mouse mammary tissue. Further investigation in obese women is warranted. Cancer Prev Res; 6(9); 886-97. (C) 2013 AACR.
C1 [Subbaramaiah, Kotha; Sue, Erika; Bhardwaj, Priya; Du, Baoheng; Hudis, Clifford A.; Dannenberg, Andrew J.] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA.
[Zhou, Xi Kathy] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY 10065 USA.
[Hudis, Clifford A.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
[Giri, Dilip] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA.
[Kopelovich, Levy] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Dannenberg, AJ (reprint author), Weill Cornell Med Coll, Dept Med, 525 East 68th St,Room F-206, New York, NY 10065 USA.
EM ksubba@med.cornell.edu; ajdannen@med.cornell.edu
FU NCI [1R01CA154481, N01-CN-43302]; NIH [UL1-RR024996]; Breast Cancer
Research Foundation; New Chapter, Inc.; Botwinick-Wolfensohn Foundation
FX This work was supported by NCI 1R01CA154481, NCI N01-CN-43302, NIH
UL1-RR024996, the Breast Cancer Research Foundation, New Chapter, Inc.,
and the Botwinick-Wolfensohn Foundation (in memory of Mr. and Mrs.
Benjamin Botwinick).
NR 49
TC 9
Z9 9
U1 0
U2 9
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD SEP
PY 2013
VL 6
IS 9
BP 886
EP 897
DI 10.1158/1940-6207.CAPR-13-0140
PG 12
WC Oncology
SC Oncology
GA 214XH
UT WOS:000324171000002
PM 23880231
ER
PT J
AU Zhang, G
He, PJ
Gaedcke, J
Ghadimi, BM
Ried, T
Yfantis, HG
Lee, DH
Hanna, N
Alexander, HR
Hussain, SP
AF Zhang, Geng
He, Peijun
Gaedcke, Jochen
Ghadimi, B. Michael
Ried, Thomas
Yfantis, Harris G.
Lee, Dong H.
Hanna, Nader
Alexander, H. Richard
Hussain, S. Perwez
TI FOXL1, a Novel Candidate Tumor Suppressor, Inhibits Tumor Aggressiveness
and Predicts Outcome in Human Pancreatic Cancer
SO CANCER RESEARCH
LA English
DT Article
ID APOPTOSIS-INDUCING LIGAND; FORKHEAD TRANSCRIPTION FACTOR;
MULTIPLE-MYELOMA PATIENTS; GENE-EXPRESSION PROFILES;
INTRAEPITHELIAL-NEOPLASIA; DUCTAL ADENOCARCINOMA; DECOY RECEPTORS;
CELL-SURVIVAL; FAS LIGAND; TRAIL
AB The forkhead box L1 (FOXL1) transcription factor regulates epithelial proliferation and development of gastrointestinal tract and has been implicated in gastrointestinal tumorigenesis in mouse models. However, the role of FOXL1 in pancreatic cancer development and progression remains to be elucidated. Here, we report that higher expression of FOXL1 is significantly associated with better clinical outcome in human pancreatic ductal adenocarcinoma (PDAC). A lower FOXL1 expression is correlated with metastasis and advanced pathologic stage of pancreatic cancer. Mechanistic analyses showed that overexpression of FOXL1 induces apoptosis and inhibits proliferation and invasion in pancreatic cancer cells, whereas silencing of FOXL1 by siRNA inhibits apoptosis and enhances tumor cell growth and invasion. Furthermore, FOXL1 overexpression significantly suppressed the growth of tumor xenografts in nude mice. FOXL1 promoted apoptosis partly through the induction of TNF-related apoptosis-inducing ligand (TRAIL) in pancreatic cancer cells. In addition, FOXL1 suppressed the transcription of zinc finger E-box-binding homeobox 1 (ZEB1), an activator of epithelial-mesenchymal transition, and the negative regulation of ZEB1 contributed to the inhibitory effect of FOXL1 on tumor cell invasion. Taken together, our findings suggest that FOXL1 expression is a candidate predictor of clinical outcome in patients with resected PDAC and it plays an inhibitory role in pancreatic tumor progression. Cancer Res; 73(17); 5416-25. (C) 2013 AACR.
C1 [Zhang, Geng; He, Peijun; Hussain, S. Perwez] NCI, Pancreat Canc Unit, Human Carcinogenesis Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Ried, Thomas] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
[Gaedcke, Jochen; Ghadimi, B. Michael] Univ Med, Dept Gen & Visceral Surg, Gottingen, Germany.
[Yfantis, Harris G.; Lee, Dong H.] Univ Maryland, Sch Med, Baltimore Vet Affairs Med Ctr, Baltimore, MD 21201 USA.
[Hanna, Nader; Alexander, H. Richard] Univ Maryland, Sch Med, Dept Surg, Div Surg Oncol, Baltimore, MD 21201 USA.
[Hanna, Nader; Alexander, H. Richard] Univ Maryland, Sch Med, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
RP Hussain, SP (reprint author), NCI, Pancreat Canc Unit, Human Carcinogenesis Lab, NIH, 37 Convent Dr,Bldg 37,Room 3044B, Bethesda, MD 20892 USA.
EM hussainp@mail.nih.gov
FU National Cancer Institute, Center for Cancer Research, NIH
FX This work is supported by Intramural Research Program of the National
Cancer Institute, Center for Cancer Research, NIH.
NR 47
TC 9
Z9 11
U1 0
U2 8
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD SEP 1
PY 2013
VL 73
IS 17
BP 5416
EP 5425
DI 10.1158/0008-5472.CAN-13-0362
PG 10
WC Oncology
SC Oncology
GA 214ER
UT WOS:000324114400013
PM 23801748
ER
PT J
AU Saud, SM
Young, MR
Jones-Hall, YL
Ileva, L
Evbuomwan, MO
Wise, J
Colburn, NH
Kim, YS
Bobe, G
AF Saud, Shakir M.
Young, Matthew R.
Jones-Hall, Yava L.
Ileva, Lilia
Evbuomwan, Moses O.
Wise, Jennifer
Colburn, Nancy H.
Kim, Young S.
Bobe, Gerd
TI Chemopreventive Activity of Plant Flavonoid Isorhamnetin in Colorectal
Cancer Is Mediated by Oncogenic Src and beta-Catenin
SO CANCER RESEARCH
LA English
DT Article
ID PROTEIN-TYROSINE KINASE; COLON-CANCER; FAMILY KINASES;
ULCERATIVE-COLITIS; C-SRC; EXPRESSION; CSK; INFLAMMATION; PREVENTION;
CELLS
AB Analysis of the Polyp Prevention Trial showed an association between an isorhamnetin-rich diet and a reduced risk of advanced adenoma recurrence; however, the mechanism behind the chemoprotective effects of isorhamnetin remains unclear. Here, we show that isorhamnetin prevents colorectal tumorigenesis of FVB/N mice treated with the chemical carcinogen azoxymethane and subsequently exposed to colonic irritant dextran sodium sulfate (DSS). Dietary isorhamnetin decreased mortality, tumor number, and tumor burden by 62%, 35%, and 59%, respectively. MRI, histopathology, and immunohistochemical analysis revealed that dietary isorhamnetin resolved the DSS-induced inflammatory response faster than the control diet. Isorhamnetin inhibited AOM/DSS-induced oncogenic c-Src activation and beta-catenin nuclear translocation, while promoting the expression of C-terminal Src kinase (CSK), a negative regulator of Src family of tyrosine kinases. Similarly, in HT-29 colon cancer cells, isorhamnetin inhibited oncogenic Src activity and beta-catenin nuclear translocation by inducing expression of csk, as verified by RNA interference knockdown of csk. Our observations suggest the chemoprotective effects of isorhamnetin in colon cancer are linked to its anti-inflammatory activities and its inhibition of oncogenic Src activity and consequential loss of nuclear beta-catenin, activities that are dependent on CSK expression. Cancer Res; 73(17); 5473-84. (C) 2013 AACR.
C1 [Saud, Shakir M.; Kim, Young S.] NCI, Nutr Sci Res Grp, Canc Prevent Div, Rockville, MD USA.
[Saud, Shakir M.; Young, Matthew R.; Colburn, Nancy H.] NCI, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21702 USA.
[Ileva, Lilia] SAIC Frederick, Small Anim Imaging Program, Frederick, MD USA.
[Wise, Jennifer] SAIC Frederick, Lab Anim Sci, Frederick, MD USA.
[Evbuomwan, Moses O.] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Jones-Hall, Yava L.] Purdue Univ, Coll Vet Med, Comparat Pathobiol Dept, W Lafayette, IN 47907 USA.
[Bobe, Gerd] Oregon State Univ, Linus Pauling Inst, Corvallis, OR 97331 USA.
[Bobe, Gerd] Oregon State Univ, Dept Anim & Rangeland Sci, Corvallis, OR 97331 USA.
RP Young, MR (reprint author), NCI, Bldg 576 Rm 100D, Frederick, MD 21702 USA.
EM youngma@mail.nih.gov
FU Office of Complementary and Alternative Medicine, Office of Dietary
Supplements; Division of Cancer Prevention; Intramural Research Program,
National Cancer Institute, NIH, Department of Health and Human Services
(DHHS), Bethesda, MD
FX This study was funded by the Office of Complementary and Alternative
Medicine, Office of Dietary Supplements, the Division of Cancer
Prevention and the Intramural Research Program, National Cancer
Institute, NIH, Department of Health and Human Services (DHHS),
Bethesda, MD.
NR 40
TC 26
Z9 27
U1 1
U2 16
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 SEP 1
PY 2013
VL 73
IS 17
BP 5473
EP 5484
DI 10.1158/0008-5472.CAN-13-0525
PG 12
WC Oncology
SC Oncology
GA 214ER
UT WOS:000324114400018
PM 23824743
ER
PT J
AU Aggarwal, M
Banerjee, T
Sommers, JA
Iannascoli, C
Pichierri, P
Shoemaker, RH
Brosh, RM
AF Aggarwal, Monika
Banerjee, Taraswi
Sommers, Joshua A.
Iannascoli, Chiara
Pichierri, Pietro
Shoemaker, Robert H.
Brosh, Robert M., Jr.
TI Werner Syndrome Helicase Has a Critical Role in DNA Damage Responses in
the Absence of a Functional Fanconi Anemia Pathway
SO CANCER RESEARCH
LA English
DT Article
ID DOUBLE-STRAND BREAKS; CROSS-LINK REPAIR; HOMOLOGOUS RECOMBINATION;
GENOMIC STABILITY; SYNDROME PROTEIN; BLOOMS-SYNDROME; WRN; INHIBITION;
DEFICIENT; ARREST
AB Werner syndrome is genetically linked to mutations in WRN that encodes a DNA helicase-nuclease believed to operate at stalled replication forks. Using a newly identified small-molecule inhibitor of WRN helicase (NSC 617145), we investigated the role of WRN in the interstrand cross-link (ICL) response in cells derived from patients with Fanconi anemia, a hereditary disorder characterized by bone marrow failure and cancer. In FA-D2(-/-) cells, NSC 617145 acted synergistically with very low concentrations of mitomycin C to inhibit proliferation in a WRN-dependent manner and induce double-strand breaks (DSB) and chromosomal abnormalities. Under these conditions, ataxia-telangiectasia mutated activation and accumulation of DNA-dependent protein kinase, catalytic subunit pS2056 foci suggested an increased number of DSBs processed by nonhomologous end-joining (NHEJ). Rad51 foci were also elevated in FA-D2(-/-) cells exposed to NSC 617145 and mitomycin C, suggesting that WRN helicase inhibition interferes with later steps of homologous recombination at ICL-induced DSBs. Thus, when the Fanconi anemia pathway is defective, WRN helicase inhibition perturbs the normal ICL response, leading to NHEJ activation. Potential implication for treatment of Fanconi anemia-deficient tumors by their sensitization to DNA cross-linking agents is discussed. Cancer Res; 73(17); 5497-507. (C) 2013 AACR.
C1 [Aggarwal, Monika; Banerjee, Taraswi; Sommers, Joshua A.; Brosh, Robert M., Jr.] NIA, Lab Mol Gerontol, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
[Shoemaker, Robert H.] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21701 USA.
[Iannascoli, Chiara; Pichierri, Pietro] Ist Super Sanita, Sect Expt & Computat Carcinogenesis, I-00161 Rome, Italy.
RP Brosh, RM (reprint author), NIA, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM broshr@mail.nih.gov
FU NIH, National Institute on Aging; National Cancer Institute; Fanconi
Anemia Research Fund
FX This work was supported by Intramural Research Program of NIH, National
Institute on Aging, and National Cancer Institute, and Fanconi Anemia
Research Fund (R.M. Brosh, Jr.).
NR 36
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U1 1
U2 11
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 SEP 1
PY 2013
VL 73
IS 17
BP 5497
EP 5507
DI 10.1158/0008-5472.CAN-12-2975
PG 11
WC Oncology
SC Oncology
GA 214ER
UT WOS:000324114400020
PM 23867477
ER
PT J
AU Wan, BB
Yin, JH
Horvath, K
Sarkar, J
Chen, Y
Wu, J
Wan, K
Lu, J
Gu, PL
Yu, EY
Lue, NF
Chang, S
Liu, Y
Lei, M
AF Wan, Bingbing
Yin, Jinhu
Horvath, Kent
Sarkar, Jaya
Chen, Yong
Wu, Jian
Wan, Ke
Lu, Jian
Gu, Peili
Yu, Eun Young
Lue, Neal F.
Chang, Sandy
Liu, Yie
Lei, Ming
TI SLX4 Assembles a Telomere Maintenance Toolkit by Bridging Multiple
Endonucleases with Telomeres
SO CELL REPORTS
LA English
DT Article
ID HOLLIDAY JUNCTION RESOLVASE; DNA-REPAIR; MAMMALIAN TELOMERES; TRF1;
LENGTH; MECHANISM; PROTEINS; CIRCLES; CELLS; LOOP
AB SLX4 interacts with several endonucleases to resolve structural barriers in DNA metabolism. SLX4 also interacts with telomeric protein TRF2 in human cells. The molecular mechanism of these interactions at telomeres remains unknown. Here, we report the crystal structure of the TRF2-binding motif of SLX4 (SLX4(TBM)) in complex with the TRFH domain of TRF2 (TRF2(TRFH)) and map the interactions of SLX4 with endonucleases SLX1, XPF, and MUS81. TRF2 recognizes a unique HxLxP motif on SLX4 via the peptide-binding site in its TRFH domain. Telomeric localization of SLX4 and associated nucleases depend on the SLX4-endonuclease and SLX4-TRF2 interactions and the protein levels of SLX4 and TRF2. SLX4 assembles an endonuclease toolkit that negatively regulates telomere length via SLX1-catalyzed nucleolytic resolution of telomere DNA structures. We propose that the SLX4-TRF2 complex serves as a double-layer scaffold bridging multiple endonucleases with telomeres for recombination-based telomere maintenance.
C1 [Wan, Bingbing; Chen, Yong; Wu, Jian; Lei, Ming] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 200031, Peoples R China.
[Wan, Bingbing; Chen, Yong; Wu, Jian; Lei, Ming] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Natl Ctr Prot Sci Shanghai, Shanghai 200031, Peoples R China.
[Wan, Bingbing; Wan, Ke; Lei, Ming] Univ Michigan, Sch Med, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA.
[Wan, Bingbing; Wan, Ke; Lei, Ming] Univ Michigan, Sch Med, Dept Biol Chem, Ann Arbor, MI 48109 USA.
[Yin, Jinhu; Horvath, Kent; Sarkar, Jaya; Lu, Jian; Liu, Yie] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21044 USA.
[Horvath, Kent] Univ Med & Dent New Jersey, New Jersey Med Sch, Grad Sch Biomed Sci, Newark, NJ 07103 USA.
[Gu, Peili; Chang, Sandy] Yale Univ, Sch Med, Dept Lab Med & Pathol, New Haven, CT 06520 USA.
[Yu, Eun Young; Lue, Neal F.] Cornell Univ, Weill Med Coll, WR Hearst Microbiol Res Ctr, Dept Microbiol & Immunol, New York, NY 10065 USA.
RP Liu, Y (reprint author), NIA, Lab Mol Gerontol, NIH, 251 Bayview Dr, Baltimore, MD 21044 USA.
EM liuyie@mail.nih.gov; leim@sibcb.ac.cn
FU Ministry of Science and Technology of China [2013CB910400]; NIA,
National Institutes of Health, USA
FX We thank Dr. J. Wade Harper for the templates of SLX4 and its
interacting nucleases and Bob Wersto, Tonya Wolf, Honwei Liu, Chorong
Song, and Cuong Nguyen for technical support. M. L. is a Howard Hughes
Medical Institute Early Career Scientist. This work was supported by
grants from the Ministry of Science and Technology of China
(2013CB910400) and the Intramural Research Program of the NIA, National
Institutes of Health, USA.
NR 24
TC 39
Z9 39
U1 1
U2 28
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD SEP
PY 2013
VL 4
IS 5
BP 861
EP 869
DI 10.1016/j.celrep.2013.08.017
PG 9
WC Cell Biology
SC Cell Biology
GA 216LZ
UT WOS:000324286300002
PM 24012755
ER
PT J
AU Wu, JJ
Liu, J
Chen, EB
Wang, JJ
Cao, L
Narayan, N
Fergusson, MM
Rovira, II
Allen, M
Springer, DA
Lago, CU
Zhang, SL
DuBois, W
Ward, T
deCabo, R
Gavrilova, O
Mock, B
Finkel, T
AF Wu, J. Julie
Liu, Jie
Chen, Edmund B.
Wang, Jennifer J.
Cao, Liu
Narayan, Nisha
Fergusson, Marie M.
Rovira, Ilsa I.
Allen, Michele
Springer, Danielle A.
Lago, Cory U.
Zhang, Shuling
DuBois, Wendy
Ward, Theresa
deCabo, Rafael
Gavrilova, Oksana
Mock, Beverly
Finkel, Toren
TI Increased Mammalian Lifespan and a Segmental and Tissue-Specific Slowing
of Aging after Genetic Reduction of mTOR Expression
SO CELL REPORTS
LA English
DT Article
ID HETEROGENEOUS MICE; OLDER ADULTS; STEM-CELLS; RAPAMYCIN; GROWTH; TOR;
DROSOPHILA; PATHWAY; DISEASE; KINASE
AB We analyzed aging parameters using a mechanistic target of rapamycin (mTOR) hypomorphic mouse model. Mice with two hypomorphic (mTOR(Delta/Delta)) alleles are viable but express mTOR at approximately 25% of wild-type levels. These animals demonstrate reduced mTORC1 and mTORC2 activity and exhibit an approximately 20% increase in median survival. While mTOR(Delta/Delta) mice are smaller than wild-type mice, these animals do not demonstrate any alterations in normalized food intake, glucose homeostasis, or metabolic rate. Consistent with their increased lifespan, mTOR(Delta/Delta) mice exhibited a reduction in a number of aging tissue biomarkers. Functional assessment suggested that, as mTOR(Delta/Delta) mice age, they exhibit a marked functional preservation in many, but not all, organ systems. Thus, in a mammalian model, while reducing mTOR expression markedly increases overall lifespan, it affects the age-dependent decline in tissue and organ function in a segmental fashion.
C1 [Wu, J. Julie; Liu, Jie; Chen, Edmund B.; Wang, Jennifer J.; Narayan, Nisha; Fergusson, Marie M.; Rovira, Ilsa I.; Lago, Cory U.; Finkel, Toren] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA.
[Allen, Michele; Springer, Danielle A.] NHLBI, Murine Phenotyping Core, NIH, Bethesda, MD 20892 USA.
[Zhang, Shuling; DuBois, Wendy; Mock, Beverly] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
[Gavrilova, Oksana] NIDDK, Mouse Metab Core, NIH, Bethesda, MD 20892 USA.
[Cao, Liu] China Med Univ, Key Lab Med Cell Biol, Shenyang 110001, Peoples R China.
[Ward, Theresa; deCabo, Rafael] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA.
RP Finkel, T (reprint author), NHLBI, Ctr Mol Med, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM finkelt@nih.gov
RI Mock, Beverly/B-3110-2015; de Cabo, Rafael/J-5230-2016;
OI Mock, Beverly/0000-0003-2479-4549; de Cabo, Rafael/0000-0002-3354-2442;
, rafael/0000-0003-2830-5693
FU NIH
FX We are grateful to Kumiko Torisu for helpful advice; Zu-Xi Yu for help
with tissue sectioning; Lauren Brinster for animal pathology advice;
William Jou and Tatyana Chanturiya for help with the metabolic testing;
and David Allison, Timothy Mark Beasley, and John Dawson for statistical
assistance. This work was supported by the NIH Intramural Research
Program.
NR 31
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U1 1
U2 28
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD SEP
PY 2013
VL 4
IS 5
BP 913
EP 920
DI 10.1016/j.celrep.2013.07.030
PG 8
WC Cell Biology
SC Cell Biology
GA 216LZ
UT WOS:000324286300008
PM 23994476
ER
PT J
AU Quax, TEF
Wolf, YI
Koehorst, JJ
Wurtzel, O
van der Oost, R
Ran, WQ
Blombach, F
Makarova, KS
Brouns, SJJ
Forster, AC
Wagner, EGH
Sorek, R
Koonin, EV
van der Oost, J
AF Quax, Tessa E. F.
Wolf, Yuri I.
Koehorst, Jasper J.
Wurtzel, Omri
van der Oost, Richard
Ran, Wenqi
Blombach, Fabian
Makarova, Kira S.
Brouns, Stan J. J.
Forster, Anthony C.
Wagner, E. Gerhart H.
Sorek, Rotem
Koonin, Eugene V.
van der Oost, John
TI Differential Translation Tunes Uneven Production of Operon-Encoded
Proteins
SO CELL REPORTS
LA English
DT Article
ID ESCHERICHIA-COLI; GENE-EXPRESSION; MESSENGER-RNAS; CODON BIAS;
TRANSCRIPTION; SEQUENCE; RIBOSOME; BACTERIA; GENOME; ARCHITECTURE
AB Clustering of functionally related genes in operons allows for coregulated gene expression in prokaryotes. This is advantageous when equal amounts of gene products are required. Production of protein complexes with an uneven stoichiometry, however, requires tuning mechanisms to generate subunits in appropriate relative quantities. Using comparative genomic analysis, we show that differential translation is a key determinant of modulated expression of genes clustered in operons and that codon bias generally is the best in silico indicator of unequal protein production. Variable ribosome density profiles of polycistronic transcripts correlate strongly with differential translation patterns. In addition, we provide experimental evidence that de novo initiation of translation can occur at intercistronic sites, allowing for differential translation of any gene irrespective of its position on a polycistronic messenger. Thus, modulation of translation efficiency appears to be a universal mode of control in bacteria and archaea that allows for differential production of operon-encoded proteins.
C1 [Quax, Tessa E. F.; Koehorst, Jasper J.; van der Oost, Richard; Blombach, Fabian; Brouns, Stan J. J.; van der Oost, John] Wageningen Univ, Microbiol Lab, NL-6703 HB Wageningen, Netherlands.
[Wolf, Yuri I.; Ran, Wenqi; Makarova, Kira S.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
[Wurtzel, Omri; Sorek, Rotem] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel.
[Forster, Anthony C.; Wagner, E. Gerhart H.] Uppsala Univ, Dept Cell & Mol Biol, S-75124 Uppsala, Sweden.
RP Quax, TEF (reprint author), Wageningen Univ, Microbiol Lab, Dreijenpl 10, NL-6703 HB Wageningen, Netherlands.
EM tessa.quax@wur.nl; john.vanderoost@wur.nl
OI Koehorst, Jasper Jan/0000-0001-8172-8981; Blombach,
Fabian/0000-0001-5337-8662
FU Netherlands Organization for Scientific Research (NWO) via an ALW TOP
grant [854.10.003]; ALW Vidi grant [864.11.005]; Ministere de
l'Enseignement Superieur et de la Recherche de France; U.S. Department
of Health and Human Services intramural program (National Library of
Medicine, NIH); Azrieli PhD fellowship; ERC-StG grant [260432]; Israeli
Science Foundation [ISF-1303/12]; Swedish Research Council; Uppsala RNA
Research Centre
FX We thank Jonathan Weissman and Gene-Wei Li (UCSF) for providing ribosome
profiling data and stimulating discussions. This project was funded by
the Netherlands Organization for Scientific Research (NWO) via an ALW
TOP grant (854.10.003) to J.v.d.O. and an ALW Vidi grant (864.11.005) to
S.J.J.B. T. E. F. Q. was supported by a fellowship from the Ministere de
l'Enseignement Superieur et de la Recherche de France. Y.I.W., W. R., K.
S. M., and E. V. K. were supported by the U.S. Department of Health and
Human Services intramural program (National Library of Medicine, NIH).
O.W. was supported by an Azrieli PhD fellowship, and R. S. was supported
by an ERC-StG grant (260432) and the Israeli Science Foundation (grant
ISF-1303/12). A. C. F. and E. G. H. W. were supported by grants from the
Swedish Research Council, including the Uppsala RNA Research Centre.
NR 45
TC 21
Z9 21
U1 1
U2 16
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD SEP
PY 2013
VL 4
IS 5
BP 938
EP 944
DI 10.1016/j.celrep.2013.07.049
PG 7
WC Cell Biology
SC Cell Biology
GA 216LZ
UT WOS:000324286300011
PM 24012761
ER
PT J
AU Chandramohan, V
Bao, XH
Keir, ST
Pegram, CN
Szafranski, SE
Piao, H
Wikstrand, CJ
McLendon, RE
Kuan, CT
Pastan, IH
Bigner, DD
AF Chandramohan, Vidyalakshmi
Bao, Xuhui
Keir, Stephen T.
Pegram, Charles N.
Szafranski, Scott E.
Piao, Hailan
Wikstrand, Carol J.
McLendon, Roger E.
Kuan, Chien-Tsun
Pastan, Ira H.
Bigner, Darell D.
TI Construction of an Immunotoxin, D2C7-(scdsFv)-PE38KDEL, Targeting EGFRwt
and EGFRvIII for Brain Tumor Therapy
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID GROWTH-FACTOR-RECEPTOR; PHASE-II TRIAL; HUMAN GLIOBLASTOMA-MULTIFORME;
INTEGRATED GENOMIC ANALYSIS; SINGLE-CHAIN IMMUNOTOXIN; MALIGNANT GLIOMA;
MONOCLONAL-ANTIBODIES; XENOGRAFTS; EXPRESSION; CELLS
AB Purpose: The EGF receptor gene (EGFR) is most frequently amplified and overexpressed, along with its deletion mutant, EGFRvIII, in glioblastoma. We tested the preclinical efficacy of the recombinant immunotoxin, D2C7-(scdsFv)-PE38KDEL, which is reactive with a 55-amino acid (AA) region present in the extracellular domain of both EGFRwt (583-637 AAs) and EGFRvIII (292-346 AAs) proteins.
Experimental Design: The binding affinity and specificity of D2C7-(scdsFv)-PE38KDEL for EGFRwt and EGFRvIII were measured by surface-plasmon resonance and flow cytometry. In vitro cytotoxicity of D2C7-(scdsFv)-PE38KDEL was measured by inhibition of protein synthesis in human EGFRwt-transfected NR6 (NR6W), human EGFRvIII-transfected NR6 (NR6M), EGFRwt-overexpressing A431-epidermoid-carcinoma, and glioblastoma xenograft cells (43, D08-0493MG, D2159MG, and D270MG). In vivo antitumor efficacy of D2C7-(scdsFv)-PE38KDEL was evaluated using 43, NR6M, and D270MG orthotopic tumor models.
Results: The KD of D2C7-(scdsFv)-PE38KDEL for EGFRwt and EGFRvIII was 1.6 x 10(-9) mol/L and 1.3 x 10(-9) mol/L, respectively. Flow cytometry with NR6W and NR6M cells confirmed the specificity of D2C7-(scdsFv)-PE38KDEL for EGFRwt and EGFRvIII. The D2C7-(scdsFv)-PE38KDEL IC50 was 0.18 to 2.5 ng/mL on cells expressing EGFRwt (NR6W, A431, 43, and D08-0493MG). The D2C7-(scdsFv)-PE38KDEL IC50 was approximately 0.25 ng/mL on EGFRvIII-expressing cells (NR6M) and on EGFRwt- and EGFRvIII-expressing glioblastoma xenograft cells (D2159MG and D270MG). Significantly, in intracranial tumor models of 43, NR6M, and D270MG, treatment with D2C7-(scdsFv)-PE38KDEL by convection-enhanced delivery prolonged survival by 310% (P = 0.006), 28% (P = 0.002), and 166% (P = 0.001), respectively.
Conclusions: In preclinical studies, the D2C7-(scdsFv)-PE38KDEL immunotoxin exhibited significant potential for treating brain tumors expressing EGFRwt, EGFRvIII, or both. (C)2013 AACR.
C1 [Chandramohan, Vidyalakshmi; Bao, Xuhui; Keir, Stephen T.; Pegram, Charles N.; Szafranski, Scott E.; Piao, Hailan; McLendon, Roger E.; Kuan, Chien-Tsun; Bigner, Darell D.] Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr, Durham, NC 27710 USA.
[Chandramohan, Vidyalakshmi; Bao, Xuhui; Keir, Stephen T.; Pegram, Charles N.; Szafranski, Scott E.; Piao, Hailan; McLendon, Roger E.; Kuan, Chien-Tsun; Bigner, Darell D.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA.
[Pastan, Ira H.] NCI, NIH, Ctr Canc Res, Mol Biol Lab, Bethesda, MD 20892 USA.
[Bao, Xuhui] Fudan Univ, Huashan Hosp, Dept Neurol, Shanghai 200433, Peoples R China.
[Wikstrand, Carol J.] Saba Univ, Sch Med, Saba, Dutch Caribbean, Netherlands.
RP Bigner, DD (reprint author), Duke Univ, Med Ctr, Dept Pathol, Box 3156,177 MSRB 1,Res Dr, Durham, NC 27710 USA.
EM darell.bigner@duke.edu
FU NIH [P50 NS020023-29, P01 CA154291-01, R37 CA011898-42, P30
CA014236-39]; Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research
FX The study was funded in part by the following NIH grants: P50
NS020023-29 (to D. D. Bigner), P01 CA154291-01 (to D. D. Bigner), R37
CA011898-42 (NCI Merit Award to D. D. Bigner), and P30 CA014236-39 (to
M. B. Kastan). This research was supported in part by grants from the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research (to I. H. Pastan).
NR 49
TC 19
Z9 20
U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD SEP 1
PY 2013
VL 19
IS 17
BP 4717
EP 4727
DI 10.1158/1078-0432.CCR-12-3891
PG 11
WC Oncology
SC Oncology
GA 213ZE
UT WOS:000324098400020
PM 23857604
ER
PT J
AU Figg, WD
Chau, CH
Madan, RA
Gulley, JL
Gao, R
Sissung, TM
Spencer, S
Beatson, M
Aragon-Ching, J
Steinberg, SM
Dahut, WL
AF Figg, William D.
Chau, Cindy H.
Madan, Ravi A.
Gulley, James L.
Gao, Rui
Sissung, Tristan M.
Spencer, Shawn
Beatson, Melony
Aragon-Ching, Jeanny
Steinberg, Seth M.
Dahut, William L.
TI Phase II Study of Satraplatin and Prednisone in Patients With Metastatic
Castration-Resistant Prostate Cancer: A Pharmacogenetic Assessment of
Outcome and Toxicity
SO CLINICAL GENITOURINARY CANCER
LA English
DT Article
DE ERCC1; Genotyping; Prostate cancer; Satraplatin; XRCC1
ID CELL LUNG-CANCER; PLATINUM-BASED CHEMOTHERAPY; NUCLEOTIDE
EXCISION-REPAIR; ADVANCED COLORECTAL-CANCER; COMPLEMENTATION GROUP-1
POLYMORPHISM; MITOXANTRONE PLUS PREDNISONE; ERCC1 CODON-118
POLYMORPHISM; EPITHELIAL OVARIAN-CANCER; ADVANCED NSCLC PATIENTS;
COMBINATION CHEMOTHERAPY
AB Genetic polymorphisms in DNA repair enzymes (excision repair cross-complementing group 1 [ERCC1] and x-ray cross-complementing group 1 [XRCC1]) may predict treatment outcome and response to platinum-based treatment. Twenty-four patients were enrolled in this single-arm study to assess the association between ERCC1 and XRCC1 gene variants and treatment outcomes with satraplatin in patients with docetaxel-refractory metastatic castration-resistant prostate cancer.
Background: We assessed the effect of excision repair cross-complementing group 1 (ERCC1) and x-ray cross-complementing group 1 (XRCC1) gene polymorphisms on treatment outcomes with satraplatin and prednisone in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel-based therapy. Patients and Methods: Twenty-four patients were enrolled in this single arm study. The primary objective was to determine if the presence of ERCC1 Asn118Asn (N118N, 500C>T, rs11615) and XRCC1 Arg399Gln (R399Q, 1301G>A, rs25487) genetic variants might be associated with an impact on progression-free survival (PFS); secondary objectives included overall response, survival, and toxicity. Results: After population stratification by race, white patients carrying heterozygous or variant genotypes at the ERCC1 C>T locus had a >3-fold longer median PFS (5.8 vs. 1.8 months; 2P = .18, adjusted) and 5-fold longer median overall survival (OS) (15.7 vs. 3.2 months; 2P = .010, adjusted) than did patients carrying only wild-type alleles. For the XRCC1 G>A variant, without regard to race, patients carrying the wild-type GG alleles had a longer PFS (9.3 months) than those carrying GA or AA alleles (2.7 months; 2P = .02). Similarly, those carrying GG alleles did not reach median OS, whereas those carrying GA or AA alleles had a median OS of 9.6 months (2P = .12, adjusted). Multivariable analysis by using Cox proportional hazards modeling demonstrated that only XRCC1 was associated with PFS. Conclusions: To our knowledge, this is the first prospective study to date in patients with metastatic castration-resistant prostate cancer that describes predictive germline polymorphisms of ERCC1 and XRCC1 for assessing the clinical activity of satraplatin. Published by Elsevier Inc.
C1 [Figg, William D.; Chau, Cindy H.; Madan, Ravi A.; Gulley, James L.; Gao, Rui; Sissung, Tristan M.; Beatson, Melony; Dahut, William L.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Spencer, Shawn] Natl Canc Inst Frederick, Clin Pharmacol Program, SAIC Frederick Inc, Bethesda, MD USA.
[Aragon-Ching, Jeanny] George Washington Univ, Med Ctr, Dept Med, Div Hematol & Oncol, Washington, DC 20037 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, CCR, NIH, Bethesda, MD 20892 USA.
RP Figg, WD (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, Bldg 10,Room 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM figgw@helix.nih.gov
RI Mendez, Pedro /J-8955-2016; Gulley, James/K-4139-2016; Figg Sr,
William/M-2411-2016;
OI Mendez, Pedro /0000-0001-6713-7907; Gulley, James/0000-0002-6569-2912;
Aragon-Ching, Jeanny/0000-0002-6714-141X
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; Intramural Research Program of the Center for
Cancer Research, National Cancer Institute, National Institutes of
Health
FX We thank the nursing staff of National Cancer Institute and the fellows
of the Medical Oncology Branch at National Cancer Institute for their
care of our patients; Eileen Curreri for data management assistance.
Most importantly, we appreciate the patients with cancer who enroll in
investigational trials to advance the knowledge of this disease. This
project has been funded in whole or in part with federal funds from the
National Cancer Institute, National Institutes of Health, under contract
number HHSN261200800001E (Shawn Spencer). This work was supported by the
Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health. This is a US Government
work. There are no restrictions on its use. The views expressed within
this article do not necessarily reflect those of the US Government.
NR 59
TC 10
Z9 10
U1 0
U2 9
PU CIG MEDIA GROUP, LP
PI DALLAS
PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA
SN 1558-7673
J9 CLIN GENITOURIN CANC
JI Clin. Genitourin. Cancer
PD SEP
PY 2013
VL 11
IS 3
BP 229
EP 237
DI 10.1016/j.clgc.2013.04.007
PG 9
WC Oncology; Urology & Nephrology
SC Oncology; Urology & Nephrology
GA 215ZX
UT WOS:000324251400003
PM 23684781
ER
PT J
AU Rojan, A
Funches, R
Regan, MM
Gulley, JL
Bubley, GJ
AF Rojan, Adam
Funches, Renee
Regan, Meredith M.
Gulley, James L.
Bubley, Glenn J.
TI Dramatic and Prolonged PSA Response After Retreatment With a PSA Vaccine
SO CLINICAL GENITOURINARY CANCER
LA English
DT Article
DE Immunologic response; PROSTVAC-VF; Revaccination
ID RESISTANT PROSTATE-CANCER; TRIAL; IMMUNOTHERAPY
C1 [Rojan, Adam; Bubley, Glenn J.] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA.
[Funches, Renee] Midatlantic Permanente Med Grp, Dept Hematol Oncol, Washington, DC USA.
[Regan, Meredith M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Gulley, James L.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Bubley, GJ (reprint author), Beth Israel Deaconess Med Ctr, CLS 449,330 Brookline Ave, Boston, MA 02215 USA.
EM gbubley@bidmc.harvard.edu
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 11
TC 2
Z9 2
U1 0
U2 1
PU CIG MEDIA GROUP, LP
PI DALLAS
PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA
SN 1558-7673
J9 CLIN GENITOURIN CANC
JI Clin. Genitourin. Cancer
PD SEP
PY 2013
VL 11
IS 3
BP 362
EP 364
DI 10.1016/j.clgc.2013.01.003
PG 3
WC Oncology; Urology & Nephrology
SC Oncology; Urology & Nephrology
GA 215ZX
UT WOS:000324251400024
PM 23791437
ER
PT J
AU Bagci, U
Jaster-Miller, K
Olivier, KN
Yao, JH
Mollura, DJ
AF Bagci, Ulas
Jaster-Miller, Kirsten
Olivier, Kenneth N.
Yao, Jianhua
Mollura, Daniel J.
TI Synergistic combination of clinical and imaging features predicts
abnormal imaging patterns of pulmonary infections
SO COMPUTERS IN BIOLOGY AND MEDICINE
LA English
DT Article
DE Infectious diseases; Parainfluenza; Pneumonias; NTM; Biomarker; Texture
analysis; Lung CT; Feature extraction; AmRMR
ID BOOSTED DECISION TREES; FEATURE-SELECTION; MUTUAL INFORMATION; DATA
SETS; DIAGNOSIS; TEXTURE; CANCER; REGRESSION
AB We designed and tested a novel hybrid statistical model that accepts radiologic image features and clinical variables, and integrates this information in order to automatically predict abnormalities in chest computed-tomography (CT) scans and identify potentially important infectious disease biomarkers. In 200 patients, 160 with various pulmonary infections and 40 healthy controls, we extracted 34 clinical variables from laboratory tests and 25 textural features from CT images. From the CT scans, pleural effusion (PE), linear opacity (or thickening) (LT), tree-in-bud (TIB), pulmonary nodules, ground glass opacity (GGO), and consolidation abnormality patterns were analyzed and predicted through clinical, textural (imaging), or combined attributes. The presence and severity of each abnormality pattern was validated by visual analysis of the CT scans. The proposed biomarker identification system included two important steps: (i) a coarse identification of an abnormal imaging pattern by adaptively selected features (AmRMR), and (ii) a fine selection of the most important features from the previous step, and assigning them as biomarkers, depending on the prediction accuracy. Selected biomarkers were used to classify normal and abnormal patterns by using a boosted decision tree (BDT) classifier. For all abnormal imaging patterns, an average prediction accuracy of 76.15% was obtained. Experimental results demonstrated that our proposed biomarker identification approach is promising and may advance the data processing in clinical pulmonary infection research and diagnostic techniques. Published by Elsevier Ltd.
C1 [Bagci, Ulas; Jaster-Miller, Kirsten; Mollura, Daniel J.] NIH, Ctr Infect Dis Imaging, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Yao, Jianhua] NIH, Clin Image Proc Serv, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Olivier, Kenneth N.] NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
RP Bagci, U (reprint author), NIH, Ctr Infect Dis Imaging, Dept Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA.
EM ulas.bagci@nih.gov
OI Bagci, Ulas/0000-0001-7379-6829
FU Center for Infectious Disease Imaging (CIDI); Intramural Program of the
National Institutes of Allergy and Infectious Diseases (NIAID);
Intramural Research Program of the National Institutes of Biomedical
Imaging and Bioengineering (NIBIB) at the National Institutes of Health
(NIH)
FX We thank Albert Wu and Omer Aras for visual scoring, and T. Palmore for
useful information on clinical variables. This research is supported by
the Center for Infectious Disease Imaging (CIDI), the Intramural Program
of the National Institutes of Allergy and Infectious Diseases (NIAID),
and the Intramural Research Program of the National Institutes of
Biomedical Imaging and Bioengineering (NIBIB) at the National Institutes
of Health (NIH). We thank Brent Foster for useful discussions on the
revised paper, and Kristine Evers for editing of this paper.
NR 30
TC 2
Z9 2
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0010-4825
J9 COMPUT BIOL MED
JI Comput. Biol. Med.
PD SEP 1
PY 2013
VL 43
IS 9
BP 1241
EP 1251
DI 10.1016/j.compbiomed.2013.06.008
PG 11
WC Biology; Computer Science, Interdisciplinary Applications; Engineering,
Biomedical; Mathematical & Computational Biology
SC Life Sciences & Biomedicine - Other Topics; Computer Science;
Engineering; Mathematical & Computational Biology
GA 214RY
UT WOS:000324154700017
PM 23930819
ER
PT J
AU Alinger, JB
Ireland, R
Bosio, CM
AF Alinger, J. B.
Ireland, R.
Bosio, C. M.
TI Bacterial driven inhibition of IL-12p40 in primary human cells via
modulation of IRF1 and IRF8 independent of GPCR signaling and IL-10
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Alinger, J. B.; Ireland, R.; Bosio, C. M.] NIAID, Immun Pulm Pathogens Sect, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RI Bosio, Catharine/D-7456-2015
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 243
EP 244
DI 10.1016/j.cyto.2013.06.007
PG 2
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700016
ER
PT J
AU Bekisz, J
Eichberg, D
Dolan, M
Zhao, TM
Zoon, KC
AF Bekisz, Joseph
Eichberg, Daniel
Dolan, Michael
Zhao, Tongmao
Zoon, Kathryn C.
TI Characterization of human interferon-alpha subtypes and mutants
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Bekisz, Joseph; Eichberg, Daniel; Zhao, Tongmao; Zoon, Kathryn C.] NIAID, Cytokine Biol Sect, NIH, Bethesda, MD 20892 USA.
[Dolan, Michael] NIAID, Bioinformat & Computat Biosci Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 247
EP 247
DI 10.1016/j.cyto.2013.06.021
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700030
ER
PT J
AU Bergamaschi, C
Chen, S
Valentin, A
Kulkarni, V
Bear, J
Rosati, M
Alicea, C
Beach, RK
Sowder, R
Chertova, E
Felber, BK
Pavlakis, GN
AF Bergamaschi, Cristina
Chen, Stephanie
Valentin, Antonio
Kulkarni, Viraj
Bear, Jenifer
Rosati, Margherita
Alicea, Candido
Beach, Rachel Kelly
Sowder, Raymond
Chertova, Elena
Felber, Barbara K.
Pavlakis, George N.
TI Heterodimeric IL-15 regulates the balance of effector and regulatory
cells, favoring anti-tumor responses
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Bergamaschi, Cristina; Valentin, Antonio; Rosati, Margherita; Beach, Rachel Kelly; Felber, Barbara K.] NCI, Human Retrovirus Pathogenesis Sect, Vaccine Branch, CCR, Frederick, MD 21701 USA.
[Chen, Stephanie; Kulkarni, Viraj; Bear, Jenifer; Alicea, Candido; Beach, Rachel Kelly; Pavlakis, George N.] NCI, Human Retrovirus Sect, Vaccine Branch, CCR, Frederick, MD 21701 USA.
[Sowder, Raymond; Chertova, Elena] SAIC Frederick Inc, Retroviral Prot Chem Core, AIDS & Canc Virus Program, FNLCR, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 247
EP 248
DI 10.1016/j.cyto.2013.06.023
PG 2
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700032
ER
PT J
AU Chen, KQ
Liu, MY
Liu, Y
Wang, CY
Yoshimura, T
Gong, WH
Le, YY
Tessarollo, L
Wang, JM
AF Chen, Keqiang
Liu, Mingyong
Liu, Ying
Wang, Chunyan
Yoshimura, Teizo
Gong, Wanghua
Le, Yingying
Tessarollo, Lino
Wang, Ji Ming
TI Signal relay by CCR2 and formylpeptide receptor-2 (Fpr2) in the
recruitment of monocyte-derived dendritic cells in allergic airway
inflammation
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Chen, Keqiang; Liu, Mingyong; Liu, Ying; Wang, Chunyan; Yoshimura, Teizo; Wang, Ji Ming] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.
[Gong, Wanghua] SAIC Frederick, Frederick, MD 21702 USA.
[Le, Yingying] Chinese Acad Sci, Inst Nutr Sci, Shanghai 200031, Peoples R China.
[Tessarollo, Lino] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 253
EP 253
DI 10.1016/j.cyto.2013.06.045
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700054
ER
PT J
AU Chong, WP
Chen, J
Silver, PB
Horai, R
Mattapallil, MJ
Zhou, R
Caspi, RR
AF Chong, Wai Po
Chen, Jun
Silver, Phyllis B.
Horai, Reiko
Mattapallil, Mary J.
Zhou, Ru
Caspi, Rachel R.
TI Reciprocal interaction between NK and DC regulates the autopathogenic
Th17 response by controlling the innate IFN-gamma/IL-27 axis
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Chong, Wai Po; Chen, Jun; Silver, Phyllis B.; Horai, Reiko; Mattapallil, Mary J.; Zhou, Ru; Caspi, Rachel R.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 254
EP 254
DI 10.1016/j.cyto.2013.06.049
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700058
ER
PT J
AU Dai, L
Lidie, KB
Chen, Q
Adelsberger, JW
Zheng, X
Huang, DW
Yang, J
Lempicki, RA
Rehman, T
Dewar, RL
Wang, YM
Hornung, RL
Canizales, KA
Lockett, SJ
Lane, HC
Imamichi, T
AF Dai, Lue
Lidie, Kristy B.
Chen, Qian
Adelsberger, Joseph W.
Zheng, Xin
Huang, DaWei
Yang, Jun
Lempicki, Richard A.
Rehman, Tauseef
Dewar, Robin L.
Wang, Yanmei
Hornung, Ronald L.
Canizales, Kelsey A.
Lockett, Stephen J.
Lane, H. Clifford
Imamichi, Tomozumi
TI IL-27 inhibits HIV-1 infection in human macrophages by down-regulating
host factor SPTBN1 during monocyte to macrophage differentiation
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Dai, Lue; Lidie, Kristy B.; Chen, Qian; Adelsberger, Joseph W.; Zheng, Xin; Huang, DaWei; Yang, Jun; Lempicki, Richard A.; Rehman, Tauseef; Dewar, Robin L.; Wang, Yanmei; Hornung, Ronald L.; Canizales, Kelsey A.; Imamichi, Tomozumi] Sci Applicat Int Corp Frederick Inc, Appl & Dev Directorate, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Lockett, Stephen J.] Sci Applicat Int Corp Frederick Inc, Adv Technol Program Directorate, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Lane, H. Clifford] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RI Lempicki, Richard/E-1844-2012
OI Lempicki, Richard/0000-0002-7059-409X
NR 0
TC 0
Z9 0
U1 0
U2 9
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 257
EP 257
DI 10.1016/j.cyto.2013.06.061
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700070
ER
PT J
AU Datta, S
AF Datta, Sandip
TI IL-20 receptor signaling inhibits cutaneous IL-1 beta and IL-17A
production to promote methicillin-resistant staphylococcus aureus
infection
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Datta, Sandip] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 257
EP 257
DI 10.1016/j.cyto.2013.06.064
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700073
ER
PT J
AU Du, N
Kwon, HJ
Li, P
Oh, J
Liao, W
Leonard, WJ
AF Du, Ning
Kwon, Hyok-Joon
Li, Peng
Oh, Jangsuk
Liao, Wei
Leonard, Warren J.
TI EGR2 is critical for peripheral Naive T cell differentiation and the
T-cell mediated response to influenza
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
NHLBI, Ctr Immunol, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 260
EP 260
DI 10.1016/j.cyto.2013.06.075
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700084
ER
PT J
AU Durum, SK
Li, WQ
Zenatti, P
Ribeiro, D
Zuurbier, L
Silva, MC
Paganin, M
Tritapoe, J
Hixon, JA
Silveira, AB
Cardoso, BA
Sarmento, LM
Correia, N
Toribio, ML
Kobarg, J
Horstmann, M
Pieters, R
Brandalise, SR
Ferrando, AA
Meijerink, JP
Yunes, JA
Barata, JT
AF Durum, Scott K.
Li, W. Q.
Zenatti, P.
Ribeiro, D.
Zuurbier, L.
Silva, M. C.
Paganin, M.
Tritapoe, J.
Hixon, J. A.
Silveira, A. B.
Cardoso, B. A.
Sarmento, L. M.
Correia, N.
Toribio, M. L.
Kobarg, J.
Horstmann, M.
Pieters, R.
Brandalise, S. R.
Ferrando, A. A.
Meijerink, J. P.
Yunes, J. A.
Barata, J. T.
TI IL-7R: Mutations in T-ALL and polymorphisms in autoimmunity
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Durum, Scott K.; Li, W. Q.; Tritapoe, J.; Hixon, J. A.] NCI, Bethesda, MD 20892 USA.
[Ribeiro, D.; Silva, M. C.; Cardoso, B. A.; Sarmento, L. M.; Correia, N.; Barata, J. T.] Univ Lisbon, P-1699 Lisbon, Portugal.
[Paganin, M.; Ferrando, A. A.] Columbia Univ, New York, NY 10027 USA.
[Toribio, M. L.] Univ Autonoma Madrid, E-28049 Madrid, Spain.
[Horstmann, M.] Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany.
[Brandalise, S. R.; Yunes, J. A.] Univ Estadual Campinas, BR-13081970 Campinas, SP, Brazil.
NR 0
TC 0
Z9 0
U1 1
U2 5
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 260
EP 261
DI 10.1016/j.cyto.2013.06.077
PG 2
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700086
ER
PT J
AU Green, DS
Bekisz, J
Dolan, M
Zoon, KC
AF Green, Daniel S.
Bekisz, Joseph
Dolan, Michael
Zoon, Kathryn C.
TI Characterization of the interferon alpha inducible protein LY6E
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Green, Daniel S.; Bekisz, Joseph; Zoon, Kathryn C.] NIAID, Cytokine Biol Sect, NIH, Bethesda, MD 20892 USA.
[Dolan, Michael] NIAID, Bioinformat & Computat Biosci Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 267
EP 267
DI 10.1016/j.cyto.2013.06.104
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700113
ER
PT J
AU Griffin, AJ
Crane, DD
Wehrly, TD
Bosio, CM
AF Griffin, Amanda J.
Crane, Debbie D.
Wehrly, Tara D.
Bosio, Catharine M.
TI Virulent Francisella tularensis do not induce arginase as a mechanism of
virulence
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Griffin, Amanda J.; Crane, Debbie D.; Wehrly, Tara D.; Bosio, Catharine M.] NIAID, Immun Pulm Pathogens Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
RI Bosio, Catharine/D-7456-2015
NR 0
TC 0
Z9 0
U1 0
U2 3
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 267
EP 267
DI 10.1016/j.cyto.2013.06.106
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700115
ER
PT J
AU Ha, HL
Wang, HS
Pisitkun, P
Kim, JC
Morasso, M
Udey, M
Siebenlist, U
AF Ha, Hve-Lin
Wang, Hongshan
Pisitkun, Prapaporn
Kim, Jin-Chul
Morasso, Maria
Udey, Mark
Siebenlist, Ulrich
TI Critical cell-type specific functions of the Il-17 receptor signaling
adaptor CIKS/ACT1 in imiquimod-induced psoriasis
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Ha, Hve-Lin; Wang, Hongshan; Pisitkun, Prapaporn; Siebenlist, Ulrich] NIAID, Immune Activat Sect, Lab Mol Immunol, Bethesda, MD 20892 USA.
[Udey, Mark] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 268
EP 269
DI 10.1016/j.cyto.2013.06.112
PG 2
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700121
ER
PT J
AU Hanson, ML
Hixon, JA
Li, WQ
Felber, BK
Anver, MR
Stewart, CA
Shen, W
McLean, M
Rottiers, P
Steidler, L
Durum, SK
AF Hanson, Miranda L.
Hixon, Julie A.
Li, Wenqing
Felber, Barbara K.
Anver, Miriam R.
Stewart, Charles A.
Shen, Wei
McLean, Mairi
Rottiers, Pieter
Steidler, Lothar
Durum, Scott K.
TI Lactococcus lactis expressing IL-27: A potential therapeutic for
inflammatory bowel disease
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Hanson, Miranda L.; Hixon, Julie A.; Li, Wenqing; Stewart, Charles A.; Shen, Wei; McLean, Mairi; Durum, Scott K.] NCI, Canc Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA.
[Felber, Barbara K.] NCI, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21701 USA.
[Anver, Miriam R.] NCI, Lab Anim Serv Program, Sci Applicat Int Corp, Ctr Canc Res, Frederick, MD 21701 USA.
[Rottiers, Pieter; Steidler, Lothar] ActoGenix NV, Zwijnaarde, Belgium.
NR 0
TC 0
Z9 0
U1 0
U2 5
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 269
EP 269
DI 10.1016/j.cyto.2013.06.115
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700124
ER
PT J
AU Harper, MS
Barrett, BS
Smith, DS
Heilman, KJ
Li, SX
Dittmer, U
Hasenkrug, KJ
Santiago, ML
AF Harper, Michael S.
Barrett, Bradley S.
Smith, Diana S.
Heilman, Karl J.
Li, Sam X.
Dittmer, Ulf
Hasenkrug, Kim J.
Santiago, Mario L.
TI Interferon-alpha therapy enhances the anti-friend virus B cell response
through Apobec3
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Harper, Michael S.; Barrett, Bradley S.; Smith, Diana S.; Heilman, Karl J.; Li, Sam X.; Santiago, Mario L.] Univ Colorado Denver, Div Infect Dis, Aurora, CO USA.
[Dittmer, Ulf] Univ Duisburg Essen, Duisburg, Germany.
[Hasenkrug, Kim J.] NIAID, Rocky Mt Labs, Hamilton, MT 59840 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 270
EP 270
DI 10.1016/j.cyto.2013.06.117
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700126
ER
PT J
AU Hodge, DL
Berthet, C
Coppola, V
Shirota, H
Reynolds, D
Sanford, M
Lin, FC
Klinman, DM
Young, HA
AF Hodge, Deborah L.
Berthet, Cyril
Coppola, Vincenzo
Shirota, Hidekazu
Reynolds, Della
Sanford, Michael
Lin, Fanching
Klinman, Dennis M.
Young, Howard A.
TI Loss of IFN-gamma 3 ' untranslated region AU-rich element affects
B220+cell populations in novel murine lupus model
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Hodge, Deborah L.; Shirota, Hidekazu; Reynolds, Della; Sanford, Michael; Lin, Fanching; Klinman, Dennis M.; Young, Howard A.] NCI, Expt Immunol Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.
[Berthet, Cyril] Oncodesign, Dijon, France.
[Coppola, Vincenzo] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA.
RI Coppola, Vincenzo/E-2917-2011
OI Coppola, Vincenzo/0000-0001-6163-1779
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 271
EP 271
DI 10.1016/j.cyto.2013.06.123
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700132
ER
PT J
AU Jin, TC
Jiang, JS
Smith, P
Xiao, TS
AF Jin, Tengchuan
Jiang, Jiansheng
Smith, Patrick
Xiao, Tsan Sam
TI Sensing of DNA by innate immune receptors
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Jin, Tengchuan; Jiang, Jiansheng; Smith, Patrick; Xiao, Tsan Sam] NIAID, Struct Immunobiol Unit, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RI Xiao, Tsan/I-7616-2013; Xiao, Tsan/A-8590-2010
OI Xiao, Tsan/0000-0001-9688-475X;
NR 0
TC 0
Z9 0
U1 0
U2 14
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 274
EP 274
DI 10.1016/j.cyto.2013.06.135
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700144
ER
PT J
AU Johnson, CL
Green, DS
Bekisz, J
Zoon, KC
AF Johnson, Chase L.
Green, Daniel S.
Bekisz, Joseph
Zoon, Kathryn C.
TI In vitro eradication of serous ovarian cancer with IFN-alpha 2 alpha and
IFN-gamma in combination with monocytes
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Johnson, Chase L.; Green, Daniel S.; Bekisz, Joseph; Zoon, Kathryn C.] NIAID, Cytokine Biol Sect, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 274
EP 274
DI 10.1016/j.cyto.2013.06.136
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700145
ER
PT J
AU Kurotaki, D
Osato, N
Nishiyama, A
Yamamoto, M
Ban, T
Sato, H
Nakabayashi, J
Umehara, M
Nakazawa, M
Miyake, N
Matsumoto, N
Ozato, K
Tamura, T
AF Kurotaki, Daisuke
Osato, Naoki
Nishiyama, Akira
Yamamoto, Michio
Ban, Tatsuma
Sato, Hideaki
Nakabayashi, Jun
Umehara, Marina
Nakazawa, Masatoshi
Miyake, Noriko
Matsumoto, Naomichi
Ozato, Keiko
Tamura, Tomohiko
TI The IRF8-KLF4 transcription factor cascade is essential for the
development of monocytes
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Kurotaki, Daisuke; Osato, Naoki; Nishiyama, Akira; Yamamoto, Michio; Ban, Tatsuma; Sato, Hideaki; Nakabayashi, Jun; Umehara, Marina; Tamura, Tomohiko] Yokohama City Univ, Grad Sch Med, Dept Immunol, Yokohama, Kanagawa 232, Japan.
[Nakazawa, Masatoshi] Yokohama City Univ, Grad Sch Med, Dept Expt Anim Sci, Yokohama, Kanagawa 232, Japan.
[Miyake, Noriko; Matsumoto, Naomichi] Yokohama City Univ, Grad Sch Med, Dept Human Genet, Yokohama, Kanagawa 232, Japan.
[Ozato, Keiko] NICHHD, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
U2 4
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 279
EP 279
DI 10.1016/j.cyto.2013.06.157
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700166
ER
PT J
AU Le Saout, C
Hasley, RB
Imamichi, H
Tcheung, L
Luckey, M
Park, H
Hu, ZH
Sneller, M
Lane, HC
Catalfamo, M
AF Le Saout, Cecile
Hasley, Rebecca B.
Imamichi, Hiromi
Tcheung, Lueng
Luckey, Megan
Park, Hyun
Hu, Zonghui
Sneller, Michael
Lane, H. Clifford
Catalfamo, Marta
TI Lymphopenia modulates levels of signal transducer and activator of
transcription-1 expression leading to enhanced CD4 T cell responsiveness
to type-I IFN
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Le Saout, Cecile; Hasley, Rebecca B.; Imamichi, Hiromi; Tcheung, Lueng; Sneller, Michael; Lane, H. Clifford; Catalfamo, Marta] NIAID, CMRS Lab Immunoregulat, NIH, Bethesda, MD 20892 USA.
[Luckey, Megan; Park, Hyun] NCI, Expt Immunol Branch, CCR, NIH, Bethesda, MD 20892 USA.
[Hu, Zonghui] NIAID, Biostat Res Branch, DCR, NIH, Bethesda, MD 20892 USA.
RI Davis, Megan/F-5339-2015
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 280
EP 280
DI 10.1016/j.cyto.2013.06.161
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700170
ER
PT J
AU Lin, B
Fraser, IDC
AF Lin, Bin
Fraser, Iain D. C.
TI Investigating the mechanism of TLR signaling crosstalk in mouse
macrophages
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Lin, Bin; Fraser, Iain D. C.] NIAID, Signaling Syst Unit, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 282
EP 282
DI 10.1016/j.cyto.2013.06.170
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700179
ER
PT J
AU Lin, FC
Saleh, B
Hodge, DL
Boelte, K
Chan, T
Keller, JP
Young, HA
AF Lin, Fanching
Saleh, Bahara
Hodge, Deborah L.
Boelte, Kimberly
Chan, Tim
Keller, Jonathon P.
Young, Howard A.
TI IFN-gamma causes aplastic anemia by altering HSC composition and
interrupting lineage differentiation
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Lin, Fanching; Saleh, Bahara; Hodge, Deborah L.; Boelte, Kimberly; Chan, Tim; Young, Howard A.] NCI, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21701 USA.
[Keller, Jonathon P.] NCI, Hematopoiesis & Stem Cell Biol Sect, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 282
EP 282
DI 10.1016/j.cyto.2013.06.171
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700180
ER
PT J
AU Meylan, F
Hawley, E
Barron, L
Barlow, J
Tan, CY
Penumetcha, P
Richard, A
Chen, X
Paul, WE
Wynn, TA
Gery, I
McKenzie, A
Siegel, RM
AF Meylan, Francoise
Hawley, Eric
Barron, Luke
Barlow, Jillian
Tan, Cuyian
Penumetcha, Pallavi
Richard, Arianne
Chen, Xi
Paul, William E.
Wynn, Thomas A.
Gery, Igal
McKenzie, Andrew
Siegel, Richard M.
TI The TNF family member TL1A: A key player in type 2 immunity in both
adaptive and innate lymphocytes
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Barron, Luke; Barlow, Jillian; Chen, Xi; Paul, William E.; Wynn, Thomas A.] NIAID, Immunopathogenesis Sect, LPD, Bethesda, MD 20892 USA.
[Barlow, Jillian; Tan, Cuyian; Chen, Xi; Paul, William E.; Gery, Igal] NEI, Expt Immunol Sect, NIH, Bethesda, MD 20892 USA.
[Barlow, Jillian; Chen, Xi; Paul, William E.; McKenzie, Andrew] Univ Cambridge, Mol Biol Lab, Cambridge, England.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 285
EP 285
DI 10.1016/j.cyto.2013.06.183
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700192
ER
PT J
AU Morrow, AN
Zoon, KC
AF Morrow, A. N.
Zoon, K. C.
TI Ribavirin enhances and prolongs IFN signaling and ISG expression in
virally-infected human lung epithelial cells
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Morrow, A. N.; Zoon, K. C.] NIAID, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 285
EP 285
DI 10.1016/j.cyto.2013.06.184
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700193
ER
PT J
AU Muchmore, B
Tang, W
Porter-Gill, P
Kohaar, I
Liu, LY
Brand, N
Park, H
Dickensheets, H
Sheikh, F
Rehermann, B
Donnelly, RP
O'Brien, TR
Prokunina-Olsson, L
AF Muchmore, Brian
Tang, Wei
Porter-Gill, Patricia
Kohaar, Indu
Liu, Luyang
Brand, Nathan
Park, Heiyoung
Dickensheets, Harold
Sheikh, Faruk
Rehermann, Barbara
Donnelly, Raymond P.
O'Brien, Thomas R.
Prokunina-Olsson, Ludmila
TI Identification and characterization of interferon-lambda 4 (IFN-lambda
4), a novel class-2 cytokine which impairs clearance of hepatitis C
virus
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Muchmore, Brian; Tang, Wei; Porter-Gill, Patricia; Kohaar, Indu; Liu, Luyang; Brand, Nathan; Prokunina-Olsson, Ludmila] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Park, Heiyoung; Rehermann, Barbara] NIDDK, Immunol Sect, Liver Dis Branch, Bethesda, MD USA.
[Dickensheets, Harold; Sheikh, Faruk; Donnelly, Raymond P.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA.
[O'Brien, Thomas R.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 7
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 286
EP 286
DI 10.1016/j.cyto.2013.06.185
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700194
ER
PT J
AU Olejnik, J
Marzi, A
Feldmann, H
Muhlberger, E
AF Olejnik, Judith
Marzi, Andrea
Feldmann, Heinz
Muehlberger, Elke
TI Differences in cytokine responses during infection with high and low
pathogenic Ebola viruses
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Olejnik, Judith; Muehlberger, Elke] Boston Univ, Dept Microbiol, Boston, MA 02215 USA.
[Olejnik, Judith; Muehlberger, Elke] Boston Univ, Natl Emerging Infect Dis Labs, Boston, MA 02215 USA.
[Marzi, Andrea; Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA.
NR 0
TC 0
Z9 0
U1 1
U2 16
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 287
EP 288
DI 10.1016/j.cyto.2013.06.192
PG 2
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700201
ER
PT J
AU Ozato, K
Yoshimi, R
Yoshida, Y
Gupta, M
Yoshii, H
Munasinghe, J
Maximova, O
Xiong, HB
Wang, HS
Morse, HC
AF Ozato, Keiko
Yoshimi, Ryusuke
Yoshida, Yuko
Gupta, Monica
Yoshii, Hiroaki
Munasinghe, Jeeva
Maximova, Olga
Xiong, Huabao
Wang, Hongsheng
Morse, Herbert C.
TI IRF8 regulates autophagy and activates microglia to exacerbate
neuroinflammation
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Ozato, Keiko; Yoshimi, Ryusuke; Yoshida, Yuko; Gupta, Monica; Yoshii, Hiroaki] NICHD, Program Genom Differentiat, NIH, Bethesda, MD USA.
[Munasinghe, Jeeva] NINDS, Lab Mol Imaging, NIH, Bethesda, MD 20892 USA.
[Maximova, Olga] NIH, Infect Dis Lab, Bethesda, MD 20892 USA.
[Xiong, Huabao] Mt Sinai Sch Med, Inst Immunol, New York, NY USA.
[Wang, Hongsheng; Morse, Herbert C.] NIAID, Immunogenet Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 1
U2 3
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 288
EP 289
DI 10.1016/j.cyto.2013.06.197
PG 2
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700206
ER
PT J
AU Rasmussen, AL
Falzarano, D
de Wit, E
Feldmann, F
Okumura, A
Scott, DP
Brining, D
Bushmaker, T
Martellaro, C
Benecke, AG
Munster, VJ
Feldmann, H
Katze, MG
AF Rasmussen, Angela L.
Falzarano, Darryl
de Wit, Emmie
Feldmann, Friederike
Okumura, Atsushi
Scott, Dana P.
Brining, Douglas
Bushmaker, Trent
Martellaro, Cynthia
Benecke, Arndt G.
Munster, Vincent J.
Feldmann, Heinz
Katze, Michael G.
TI Transcriptional signatures of pathogenesis and successful type I
interferon and ribavirin therapy in a rhesus macaque model of MERS-CoV
infection
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Rasmussen, Angela L.; Okumura, Atsushi; Katze, Michael G.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA.
[Falzarano, Darryl; de Wit, Emmie; Martellaro, Cynthia; Feldmann, Heinz] Dis Modeling & Transmiss, Hamilton, MT USA.
[Feldmann, Friederike] NIAID, Off Operat Management, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT USA.
[Scott, Dana P.; Brining, Douglas] NIAID, Rocky Mt Vet Branch, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT USA.
[Bushmaker, Trent; Munster, Vincent J.] NIAID, Virus Ecol Units, Virol Lab, Div Intramural Res,NIH,Rocky Mt Labs, Hamilton, MT USA.
[Benecke, Arndt G.] Univ Paris 06, Ctr Natl Rech Sci, UMR7224, Paris, France.
RI Okumura, Atsushi/E-8012-2015
OI Okumura, Atsushi/0000-0002-7779-3059
NR 0
TC 0
Z9 0
U1 0
U2 3
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 291
EP 292
DI 10.1016/j.cyto.2013.06.209
PG 2
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700218
ER
PT J
AU Ren, M
Li, P
Zheng, M
Peltz, G
Leonard, WJ
AF Ren, Min
Li, Peng
Zheng, Ming
Peltz, Gary
Leonard, Warren J.
TI Towards the identification novel regulators for Th1 differentiation by
computational genetics
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Ren, Min; Li, Peng; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Zheng, Ming; Peltz, Gary] Stanford Univ, Dept Anesthesia, Sch Med, Stanford, CA 94305 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 292
EP 292
DI 10.1016/j.cyto.2013.06.212
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700221
ER
PT J
AU Roychoudhuri, R
Hirahara, K
Mousavi, K
Clever, D
Bonelli, M
Sciume, G
Zare, H
Vahedi, G
Klebanoff, C
Sartorelli, V
Kanno, Y
Gattinoni, L
Nakamura, A
Muto, A
O'Shea, J
Restifo, N
AF Roychoudhuri, R.
Hirahara, K.
Mousavi, K.
Clever, D.
Bonelli, M.
Sciume, G.
Zare, H.
Vahedi, G.
Klebanoff, C.
Sartorelli, V.
Kanno, Y.
Gattinoni, L.
Nakamura, A.
Muto, A.
O'Shea, J.
Restifo, N.
TI BACH2 represses effector differentiation and cytokine expression to
stabilize T-reg-mediated immune homeostasis
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Roychoudhuri, R.; Clever, D.; Klebanoff, C.; Gattinoni, L.; Restifo, N.] NCI, NIH, Bethesda, MD 20892 USA.
[Hirahara, K.; Mousavi, K.; Bonelli, M.; Sciume, G.; Zare, H.; Vahedi, G.; Sartorelli, V.; Kanno, Y.; O'Shea, J.] NIAMSD, Bethesda, MD 20892 USA.
[Nakamura, A.; Muto, A.] Tohoku Univ, Sendai, Miyagi 980, Japan.
RI Hirahara, Kiyoshi/E-2460-2017
OI Hirahara, Kiyoshi/0000-0002-9128-9449
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 294
EP 294
DI 10.1016/j.cyto.2013.06.220
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700229
ER
PT J
AU Salerno, F
Engels, S
Zhao, WQ
Hodge, D
Young, HA
Medema, JP
Wolkers, MC
AF Salerno, Fiamma
Engels, Sander
Zhao, Wanqi
Hodge, Deborah
Young, Howard A.
Medema, Jan Paul
Wolkers, Monika C.
TI Post-transcriptional regulation of interferon gamma in memory CD8(+) T
cells
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Salerno, Fiamma; Engels, Sander; Zhao, Wanqi; Wolkers, Monika C.] Sanquin Res, Dept Hematopoiesis, Amsterdam, Netherlands.
[Hodge, Deborah; Young, Howard A.] NCI, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21701 USA.
[Medema, Jan Paul] Univ Amsterdam, Acad Med Ctr, Ctr Expt Mol Med, Lab Expt Oncol & Radiobiol LEXOR, NL-1105 AZ Amsterdam, Netherlands.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 295
EP 295
DI 10.1016/j.cyto.2013.06.224
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700233
ER
PT J
AU Sandler, NG
Zhu, RT
Estes, JD
Boritz, E
Rao, S
Lifson, JD
Levin, D
Schreiber, G
Langer, JA
Douek, DC
AF Sandler, Netanya G.
Zhu, Richard T.
Estes, Jacob D.
Boritz, Eli
Rao, Srinivas
Lifson, Jeffrey D.
Levin, Doron
Schreiber, Gideon
Langer, Jerome A.
Douek, Daniel C.
TI A novel type I interferon antagonist has in vivo efficacy in a model of
SIV infection in rhesus macaques
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Sandler, Netanya G.; Zhu, Richard T.; Boritz, Eli; Rao, Srinivas; Douek, Daniel C.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Estes, Jacob D.; Lifson, Jeffrey D.] Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Frederick, MD USA.
[Levin, Doron; Schreiber, Gideon] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel.
[Langer, Jerome A.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pharmacol, Piscataway, NJ 08854 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 296
EP 296
DI 10.1016/j.cyto.2013.06.226
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700235
ER
PT J
AU Sasaki, H
Kurotak, D
Sato, H
Morse, HC
Ozato, K
Tamura, T
AF Sasaki, Haruka
Kurotak, Daisuke
Sato, Hideaki
Morse, Herbert C.
Ozato, Keiko
Tamura, Tomohiko
TI The transcription factor IRF8 is required for the development of
basophils
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Sasaki, Haruka; Kurotak, Daisuke; Sato, Hideaki; Tamura, Tomohiko] Yokohama City Univ, Grad Sch Med, Dept Immunol, Yokohama, Kanagawa 232, Japan.
[Morse, Herbert C.] NIAID, Immunogenet Lab, NIH, Bethesda, MD 20892 USA.
[Ozato, Keiko] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 296
EP 296
DI 10.1016/j.cyto.2013.06.229
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700238
ER
PT J
AU Schmeisser, H
Fey, SB
Horowitz, J
Fischer, ER
Balinsky, CA
Miyake, K
Bekisz, J
Snow, AL
Zoon, KC
AF Schmeisser, Hana
Fey, Samuel B.
Horowitz, Julie
Fischer, Elizabeth R.
Balinsky, Corey A.
Miyake, Kotaro
Bekisz, Joseph
Snow, Andrew L.
Zoon, Kathryn C.
TI MTOR-signaling pathway plays a role in induction of autophagy by type I
interferons
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Schmeisser, Hana; Fey, Samuel B.; Horowitz, Julie; Balinsky, Corey A.; Miyake, Kotaro; Bekisz, Joseph; Zoon, Kathryn C.] NIAID, NIH, Cytokine Biol Sect, Bethesda, MD 20892 USA.
[Fischer, Elizabeth R.] NIAID, NIH, Rocky Mt Labs, Res Technol Sect, Hamilton, MT USA.
[Snow, Andrew L.] Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 297
EP 297
DI 10.1016/j.cyto.2013.06.231
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700240
ER
PT J
AU Silverman, RH
Zhang, R
Jha, BK
Ogden, KM
Dong, BH
Elliott, R
Zhao, L
Patton, JT
Weiss, SR
AF Silverman, Robert H.
Zhang, Rong
Jha, Babal K.
Ogden, Kristen M.
Dong, Beihua
Elliott, Ruth
Zhao, Ling
Patton, John T.
Weiss, Susan R.
TI Homologous 2 ',5 '-phosphodiesterases from disparate RNA viruses
antagonize antiviral innate immunity
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Silverman, Robert H.; Jha, Babal K.; Dong, Beihua] Cleveland Clin, Dept Canc Biol, Lerner Res Inst, Cleveland, OH 44106 USA.
[Zhang, Rong; Elliott, Ruth; Zhao, Ling; Weiss, Susan R.] Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Ogden, Kristen M.; Patton, John T.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RI Patton, John/P-1390-2014
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 300
EP 301
DI 10.1016/j.cyto.2013.06.247
PG 2
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700256
ER
PT J
AU Wan, ECK
Oh, J
Li, P
West, EE
Wong, EA
Andraski, AB
Spolski, R
Yu, ZX
He, JP
Kelsall, BL
Leonard, WJ
AF Wan, Edwin Chi-Keung
Oh, Jangsuk
Li, Peng
West, Erin E.
Wong, Elizabeth A.
Andraski, Allison B.
Spolski, Rosanne
Yu, Zu-Xi
He, Jianping
Kelsall, Brian L.
Leonard, Warren J.
TI The cytokines IL-21 and GM-CSF have opposing regulatory roles in the
apoptosis of conventional dendritic cells
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Wan, Edwin Chi-Keung; Oh, Jangsuk; Li, Peng; West, Erin E.; Wong, Elizabeth A.; Andraski, Allison B.; Spolski, Rosanne; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Yu, Zu-Xi] NHLBI, Pathol Core, NIH, Bethesda, MD 20892 USA.
[He, Jianping; Kelsall, Brian L.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
U2 3
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 307
EP 307
DI 10.1016/j.cyto.2013.06.273
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700282
ER
PT J
AU Wang, HY
Ma, CA
Zhao, YG
Fan, XY
Zhou, Q
Edmonds, P
Uzel, G
Oliveria, JB
Orange, J
Jain, A
AF Wang, Hong-Ying
Ma, Chi A.
Zhao, Yongge
Fan, Xiying
Zhou, Qing
Edmonds, Pamela
Uzel, Gulbu
Oliveria, Joao Bosco
Orange, Jordan
Jain, Ashish
TI Antibody deficiency associated with an inherited autosomal dominant
mutation in TWEAK
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Wang, Hong-Ying; Ma, Chi A.; Zhao, Yongge; Fan, Xiying; Edmonds, Pamela; Jain, Ashish] NIAID, Host Def Lab, Bethesda, MD 20892 USA.
[Uzel, Gulbu] NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
[Oliveria, Joao Bosco] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Orange, Jordan] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 308
EP 308
DI 10.1016/j.cyto.2013.06.276
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700285
ER
PT J
AU Whibley, N
Mamo, AJ
Traggiai, E
Kolbinger, F
Vogel, B
Kammuller, M
Siebenlist, U
Gaffen, SL
AF Whibley, Natasha
Mamo, Anna J.
Traggiai, Elisabetta
Kolbinger, Frank
Vogel, Beate
Kammueller, Michael
Siebenlist, Ulrich
Gaffen, Sarah L.
TI Experimental analysis of acute murine oral candidiasis after in vivo
Anti-IL-17A/IL-17F treatment and in knockout mice
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Whibley, Natasha; Mamo, Anna J.; Gaffen, Sarah L.] Univ Pittsburgh, Div Rheumatol & Clin Immunol, Pittsburgh, PA 15260 USA.
[Traggiai, Elisabetta; Kolbinger, Frank; Vogel, Beate; Kammueller, Michael] Novartis Inst Biomed Res, Basel, Switzerland.
[Siebenlist, Ulrich] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 309
EP 309
DI 10.1016/j.cyto.2013.06.282
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700291
ER
PT J
AU Zaritsky, LA
Zoon, KC
AF Zaritsky, Luna A.
Zoon, Kathryn C.
TI The differential regulation of the interferon alpha subtypes in response
to viral infection
SO CYTOKINE
LA English
DT Meeting Abstract
CT Annual Joint Conference of the International-Cytokine-Society and the
International-Society-for-Interferon-and-Cytokine-Research
CY SEP 29-OCT 03, 2013
CL San Francisco, CA
SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res
C1 [Zaritsky, Luna A.; Zoon, Kathryn C.] NIAID, Cytokine Biol Sect, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD SEP
PY 2013
VL 63
IS 3
SI SI
BP 313
EP 313
DI 10.1016/j.cyto.2013.06.298
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 212WO
UT WOS:000324013700307
ER
PT J
AU Blumberg, S
Lloyd-Smith, JO
AF Blumberg, S.
Lloyd-Smith, J. O.
TI Comparing methods for estimating R-0 from the size distribution of
subcritical transmission chains
SO EPIDEMICS
LA English
DT Article
DE Stuttering chain; Basic reproductive number; Transmission heterogeneity;
Imperfect observation; Measles
ID INFECTIOUS-DISEASES; BRANCHING-PROCESSES; MEASLES ELIMINATION;
UNITED-STATES; SURVEILLANCE; VACCINATION; EMERGENCE; OUTBREAKS;
POLIOMYELITIS; IMMUNIZATION
AB Many diseases exhibit subcritical transmission (i.e. 0 < R-0 < 1) so that infections occur as self-limited 'stuttering chains'. Given an ensemble of stuttering chains, information about the number of cases in each chain can be used to infer R-0, which is of crucial importance for monitoring the risk that a disease will emerge to establish endemic circulation. However, the challenge of imperfect case detection has led authors to adopt a variety of work-around measures when inferring R-0, such as discarding data on isolated cases or aggregating intermediate-sized chains together. Each of these methods has the potential to introduce bias, but a quantitative comparison of these approaches has not been reported. By adapting a model based on a negative binomial offspring distribution that permits a variable degree of transmission heterogeneity, we present a unified analysis of existing R-0 estimation methods. Simulation studies show that the degree of transmission heterogeneity, when improperly modeled, can significantly impact the bias of R-0 estimation methods designed for imperfect observation. These studies also highlight the importance of isolated cases in assessing whether an estimation technique is consistent with observed data. Analysis of data from measles outbreaks shows that likelihood scores are highest for models that allow a flexible degree of transmission heterogeneity. Aggregating intermediate sized chains often has similar performance to analyzing a complete chain size distribution. However, truncating isolated cases is beneficial only when surveillance systems clearly favor full observation of large chains but not small chains. Meanwhile, if data on the type and proportion of cases that are unobserved were known, we demonstrate that maximum likelihood inference of R-0 could be adjusted accordingly. This motivates the need for future empirical and theoretical work to quantify observation error and incorporate relevant mechanisms into stuttering chain models used to estimate transmission parameters. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Blumberg, S.; Lloyd-Smith, J. O.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Blumberg, S.; Lloyd-Smith, J. O.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA USA.
[Blumberg, S.] Univ Calif San Francisco, Francis I Proctor Fdn, San Francisco, CA 94143 USA.
RP Blumberg, S (reprint author), Univ Calif San Francisco, Francis I Proctor Fdn, 95 Kirkham St, San Francisco, CA 94143 USA.
EM blumberg.seth@gmail.com; jlloydsmith@ucla.edu
RI Lloyd-Smith, James/K-4080-2012
OI Lloyd-Smith, James/0000-0001-7941-502X
FU RAPIDD program of the Science and Technology Directorate, Department of
Homeland Security; Fogarty International Center, National Institutes of
Health; National Science Foundation [EF-0928690, PHY05-51164]; National
Institute of Health MIDAS program (Modeling Infectious Disease Agent
Study) [NIH NIGMS 1-U01-GM087728]; De Logi Chair in Biological Sciences
FX Feedback provided by anonymous reviewers lead to substantial
improvements of this manuscript. Financial support was provided by the
RAPIDD program of the Science and Technology Directorate, Department of
Homeland Security, the Fogarty International Center, National Institutes
of Health, and by the National Science Foundation under grants
EF-0928690 and PHY05-51164. SB is also grateful to the National
Institute of Health MIDAS program (Modeling Infectious Disease Agent
Study, grant number NIH NIGMS 1-U01-GM087728). JLS is also grateful for
the support of the De Logi Chair in Biological Sciences.
NR 33
TC 11
Z9 11
U1 3
U2 19
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1755-4365
J9 EPIDEMICS-NETH
JI Epidemics
PD SEP
PY 2013
VL 5
IS 3
BP 131
EP 145
DI 10.1016/j.epidem.2013.05.002
PG 15
WC Infectious Diseases
SC Infectious Diseases
GA 213ZX
UT WOS:000324100600002
PM 24021520
ER
PT J
AU Silbergleit, R
Lowenstein, D
Durkalski, V
Conwit, R
AF Silbergleit, Robert
Lowenstein, Daniel
Durkalski, Valerie
Conwit, Robin
CA NETT Investigators
TI Lessons from the RAMPART study-and which is the best route of
administration of benzodiazepines in status epilepticus
SO EPILEPSIA
LA English
DT Article
DE Midazolam; Lorazepam; Comparative efficacy; Emergency medical services;
Intramuscular
ID DIAZEPAM; MIDAZOLAM; TRIALS
AB Early treatment of prolonged seizures with benzodiazepines given intravenously by paramedics in the prehospital setting had been shown to be associated with improved outcomes, but the comparative efficacy and safety of an intramuscular (IM) route, which is faster and consistently achievable, was previously unknown. RAMPART (the Rapid Anticonvulsant Medication Prior to Arrival Trial) was a double-blind randomized clinical trial to determine if the efficacy of intramuscular (IM) midazolam is noninferior by a margin of 10% to that of intravenous (IV) lorazepam in patients treated by paramedics for status epilepticus (SE). In children and adults with >5min of convulsions and who are still seizing at paramedic arrival, midazolam administered by IM autoinjector was noninferior to IV lorazepam on the primary efficacy outcome with comparable safety. Patients treated with IM midazolam were more likely to have stopped seizing at emergency department (ED) arrival, without emergency medical services (EMS) rescue therapy, and were less likely to require any hospitalization or admission to an intensive care unit. Lessons from the RAMPART study's findings and potential implications on clinical practice, on the potential role of other routes of administration, on the effect of timing of interventions, and on future clinical trials are discussed.
C1 [Silbergleit, Robert] Univ Michigan, Dept Emergency Med, Ann Arbor, MI 48105 USA.
[Lowenstein, Daniel] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
[Durkalski, Valerie] Med Univ S Carolina, Dept Publ Hlth Sci, Coll Med, Charleston, SC 29425 USA.
[Conwit, Robin] NINDS, NIH, Bethesda, MD 20892 USA.
RP Silbergleit, R (reprint author), Univ Michigan, Dept Emergency Med, 24 Frank Lloyd wright Dr, Ann Arbor, MI 48105 USA.
EM Robert.silbergleit@umich.edu
FU National Institute of Neurological Disorders and Stroke (NINDS)
[5U01NS056975-04]; Office of the Director, National Institutes of Health
(OD); BARDA; NIH CounterACT program
FX This work is supported by award 5U01NS056975-04 from the National
Institute of Neurological Disorders and Stroke (NINDS), the Office of
the Director, National Institutes of Health (OD), BARDA, and the NIH
CounterACT program. This trial is registered with Clinical Trials.gov
(NCT00809146).
NR 7
TC 12
Z9 12
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0013-9580
J9 EPILEPSIA
JI Epilepsia
PD SEP
PY 2013
VL 54
SU 6
SI SI
BP 74
EP 77
DI 10.1111/epi.12284
PG 4
WC Clinical Neurology
SC Neurosciences & Neurology
GA 210JA
UT WOS:000323826600022
PM 24001080
ER
PT J
AU Horvath, KA
AF Horvath, Keith A.
TI Welcome (bienvenida, bienvenue, willkommen, pryzwitanie, accoglienza,
welkom) to the new EACTS cardiac surgery database
SO EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY
LA English
DT Editorial Material
DE Database; European cardiac surgery; Outcomes
C1 [Horvath, Keith A.] NIH, NHLBI Cardiothorac Surg Res Program, Bethesda, MD 20892 USA.
RP Horvath, KA (reprint author), 10 Ctr Dr,MSC 1550,10-B1D47, Bethesda, MD 20892 USA.
EM khorvath@nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1010-7940
J9 EUR J CARDIO-THORAC
JI Eur. J. Cardio-Thorac. Surg.
PD SEP
PY 2013
VL 44
IS 3
BP E181
EP E181
DI 10.1093/ejcts/ezt323
PG 1
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 204FL
UT WOS:000323350400004
PM 23786915
ER
PT J
AU Shaffer, BC
Modric, M
Stetler-Stevenson, M
Arthur, DC
Steinberg, SM
Liewehr, DJ
Fowler, DH
Gale, RP
Bishop, MR
Pavletic, SZ
AF Shaffer, Brian C.
Modric, Marko
Stetler-Stevenson, Maryalice
Arthur, Diane C.
Steinberg, Seth M.
Liewehr, David J.
Fowler, Daniel H.
Gale, Robert P.
Bishop, Michael R.
Pavletic, Steven Z.
TI Rapid complete donor lymphoid chimerism and graft-versus-leukemia effect
are important in early control of chronic lymphocytic leukemia
SO EXPERIMENTAL HEMATOLOGY
LA English
DT Article
ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; MINIMAL RESIDUAL
DISEASE; ALLOGENEIC TRANSPLANTATION; PROGRESSION-FREE; CLL3X TRIAL;
ENGRAFTMENT; MALIGNANCIES; SURVIVAL; CHEMOTHERAPY
AB Eradication of minimal residual disease (MRD) after allotransplantation in persons with chronic lymphocytic leukemia (CLL) is associated with lower rates of relapse. Rapid engraftment of donor lymphocyte elements can contribute to MRD control, but it remains unclear whether this strategy will benefit patients. In this study, we report the incidence of MRD eradication and graft-versus-host disease (GvHD) in persons with rapid versus later donor T lymphocyte engraftment after lymphodepleting chemotherapy and reduced intensity conditioning (RIC) allotransplantation. Twenty-seven subjects received lymphodepleting chemotherapy to facilitate donor engraftment followed by fludarabine and cyclophosphamide RIC and a blood cell allograft. MRD was monitored by multicolor flow cytometry after transplantation. Complete donor T lymphoid chimerism (TLC) and myeloid chimerism (MC) were achieved in 25 subjects at a median of 28 days (range, 14-60 days) and 21 days (range, 14-180 days), respectively. Achieving complete donor TLC by day 14 versus day 28 or later correlated with occurrence of grade 2 or higher acute GvHD (90% [95% confidence interval {CI}, 78-100%] versus 35% [95% CI, 16-54%]; p = 0.014) and better control of MRD in the bone marrow at day 100, median 0% (range, 0-0.1%) versus 8.5% (range, 0-92%; p = 0.016). Among 11 persons with early donor TLC, none had progressive disease, and seven died of treatment -related mortality (TRM). In persons with later development of TLC, 8 of 16 had progressive disease and 2 died of TRM. Time to donor myeloid chimerism had no effect on outcomes. Rapid establishment of donor TLC resulted in more complete eradication of early MRD, but greater incidence of acute GvHD and TRM in persons with CLL undergoing RIC allotransplantation. Published by Elsevier Inc. on behalf of ISEH - Society for Hematology and Stem Cells.
C1 [Shaffer, Brian C.; Fowler, Daniel H.; Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Modric, Marko; Stetler-Stevenson, Maryalice; Arthur, Diane C.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Steinberg, Seth M.; Liewehr, David J.] NCI, Biostat & Data Management Sect, Off Clin Director, NIH, Rockville, MD USA.
[Gale, Robert P.] Univ London Imperial Coll Sci Technol & Med, Dept Med, Div Expt Med, Haematol Sect, London, England.
[Bishop, Michael R.] Univ Chicago, Div Hematol & Oncol, Chicago, IL 60637 USA.
RP Shaffer, BC (reprint author), Expt Transplantat & Immunol Branch, 10 Ctr Dr,Bldg 10 CRC,Room 3-3248, Bethesda, MD 20892 USA.
EM shafferbc@mail.nih.gov
FU Center for Cancer Research, the Intramural Program of the National
Cancer Institute, National Institutes of Health; National Institutes of
Health Research Biomedical Research Centre
FX This work was supported by the Center for Cancer Research, the
Intramural Program of the National Cancer Institute, National Institutes
of Health. R.P.G. acknowledges support from the National Institutes of
Health Research Biomedical Research Centre funding scheme.
NR 35
TC 6
Z9 6
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0301-472X
J9 EXP HEMATOL
JI Exp. Hematol.
PD SEP
PY 2013
VL 41
IS 9
BP 772
EP 778
DI 10.1016/j.exphem.2013.04.015
PG 7
WC Hematology; Medicine, Research & Experimental
SC Hematology; Research & Experimental Medicine
GA 217KU
UT WOS:000324359200003
PM 23689118
ER
PT J
AU Uchida, N
Hsieh, MM
Washington, KN
Tisdale, JF
AF Uchida, Naoya
Hsieh, Matthew M.
Washington, Kareem N.
Tisdale, John F.
TI Efficient transduction of human hematopoietic repopulating cells with a
chimeric HIV1-based vector including SIV capsid
SO EXPERIMENTAL HEMATOLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; GENE-THERAPY; LENTIVIRAL VECTOR;
STEM-CELLS; RESTRICTION FACTORS; TRIM5-ALPHA; PROTEASOME; ACTIVATION;
HIV-1; INHIBITION
AB Innate immune factors, such as TRIM5 alpha and cyclophilin A (CypA), act as a major restriction factor of retroviral infection among species. When HIV1 infects human cells, HIV1 capsid binds to human CypA to escape from human TRIM5 alpha restriction. However, in rhesus cells, the mismatch between HIV1 capsid and rhesus CypA is recognized by rhesus TRIM5 alpha to reduce HIV1 infectivity through proteasomal degradation. To circumvent this block, we previously developed a chimeric HIV1 vector (HIV) that substituted HIV1 capsid with SIV capsid, and it significantly increased transduction efficiency for nonhuman primate cells. In this study, we evaluated whether the chi HIV vector efficiently transduces human cells, and the transduction efficiency might increase by a CypA inhibitor (cyclosporine) and a proteasome inhibitor (MG132). The chi HIV vector could transduce human CD34(+) cells, as efficiently as the HIV1 vector, in vitro and in xenograft mice, even in the mismatch between SIV capsid and human CypA. Cyclosporine decreased transduction efficiency with the HIV1 vector, whereas it slightly increased transduction efficiency with the chi HIV vector in human CD34(+) cells. MG132 increased transduction efficiency with both chi HIV and HIV1 vectors in the same manner. However, MG132 was toxic to human CD34(+) cells at high concentrations, and both drugs had a small range of effective dosage. These findings demonstrate that both chi HIV and HIV1 vectors have similar transduction efficiency for human hematopoietic repopulating cells, suggesting that the chi HIV vector escapes from TRIM5 alpha restriction, which is independent of human CypA. Published by Elsevier Inc. on behalf of ISEH - Society for Hematology and Stem Cells.
C1 [Uchida, Naoya; Hsieh, Matthew M.; Washington, Kareem N.; Tisdale, John F.] NIDDK, Mol & Clin Hematol Branch, NHLBI, NIH, Bethesda, MD USA.
[Washington, Kareem N.] Howard Univ, Coll Med, Howard Univ Hosp, Dept Pediat & Child Hlth,Div Genet & Human Genet, Washington, DC USA.
RP Tisdale, JF (reprint author), Mol & Clin Hematol Branch, 9000 Rockville Pike,Bldg 10,9N112, Bethesda, MD 20892 USA.
EM johntis@mail.nih.gov
FU National Heart, Lung, and Blood Institute; National Institute of
Diabetes, Digestive, and Kidney Diseases at the National Institutes of
Health
FX We thank Hayato Unno for help with this study. This work was supported
by the intramural research program of the National Heart, Lung, and
Blood Institute and the National Institute of Diabetes, Digestive, and
Kidney Diseases at the National Institutes of Health.
NR 33
TC 5
Z9 5
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0301-472X
J9 EXP HEMATOL
JI Exp. Hematol.
PD SEP
PY 2013
VL 41
IS 9
BP 779
EP 788
DI 10.1016/j.exphem.2013.04.014
PG 10
WC Hematology; Medicine, Research & Experimental
SC Hematology; Research & Experimental Medicine
GA 217KU
UT WOS:000324359200004
PM 23665451
ER
PT J
AU Kubinak, JL
Ruff, JS
Cornwall, DH
Middlebrook, EA
Hasenkrug, KJ
Potts, WK
AF Kubinak, J. L.
Ruff, J. S.
Cornwall, D. H.
Middlebrook, E. A.
Hasenkrug, K. J.
Potts, W. K.
TI Experimental viral evolution reveals major histocompatibility complex
polymorphisms as the primary host factors controlling pathogen
adaptation and virulence
SO GENES AND IMMUNITY
LA English
DT Article
DE MHC; experimental evolution; serial passage; host-pathogen
ID CYTOTOXIC T-LYMPHOCYTES; EMERGING INFECTIOUS-DISEASES; CAPTIVE BREEDING
PROGRAMS; GENETIC DIVERSITY; MHC POLYMORPHISM; ESCAPE MUTATIONS;
LABORATORY MOUSE; VIRUS-INFECTION; HUMAN HEALTH; SELECTION
AB Using an experimental evolution approach, we recently demonstrated that the mouse-specific pathogen Friend virus (FV) complex adapted to specific major histocompatibility complex (MHC) genotypes, which resulted in fitness tradeoffs when viruses were exposed to hosts possessing novel MHC polymorphisms. Here we report the analysis of patterns of pathogen adaptation and virulence evolution from viruses adapting to one of three hosts that differ across the entire genome (A/WySn, DBA/2J and BALB/c). We found that serial passage of FV complex through these mouse genotypes resulted in significant increases in pathogen fitness (156-fold) and virulence (11-fold). Adaptive responses by post-passage viruses also resulted in host-genotype-specific patterns of adaptation. To evaluate the relative importance of MHC versus non-MHC polymorphisms as factors influencing pathogen adaptation and virulence, we compared the magnitude of fitness tradeoffs incurred by post-passage viruses when infecting hosts possessing either novel MHC polymorphisms alone or hosts possessing novel MHC and non-MHC polymorphisms. MHC polymorphisms alone accounted for 71% and 83% of the total observed reductions in viral fitness and virulence in unfamiliar host genotypes, respectively. Strikingly, these data suggest that genetic polymorphisms within the MHC, a gene region representing only similar to 0.1% of the genome, are major host factors influencing pathogen adaptation and virulence evolution.
C1 [Kubinak, J. L.; Ruff, J. S.; Cornwall, D. H.; Middlebrook, E. A.; Potts, W. K.] Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA.
[Kubinak, J. L.] Univ Utah, Dept Pathol, Salt Lake City, UT 84112 USA.
[Hasenkrug, K. J.] NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA.
RP Kubinak, JL (reprint author), Univ Utah, Dept Biol, 257 South 1400 East, Salt Lake City, UT 84112 USA.
EM jason.kubinak@path.utah.edu
OI Cornwall, Douglas/0000-0002-8536-3139; Potts, Wayne/0000-0003-4137-0326
FU National Science Foundation [DEB 0918969, DEB 0910052, DGE 08-41233]
FX This work was supported by National Science Foundation Grant DEB 0918969
(to WKP and Dr Fred Adler); National Science Foundation Doctoral
Dissertation Improvement Grant DEB 0910052 (to JLK and WKP); and
National Science Foundation Educational Outreach Grant DGE 08-41233 (to
JLK and JSR). We thank Dr Sandra Ruscetti for her useful insights
regarding FV complex as well as her generous provision of reagents
throughout these experiments. We also thank Linda Morrison for her help
in the design and optimization of assays. Finally, we thank two
anonymous reviewers for their constructive comments during manuscript
preparation.
NR 42
TC 5
Z9 5
U1 0
U2 28
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1466-4879
J9 GENES IMMUN
JI Genes Immun.
PD SEP
PY 2013
VL 14
IS 6
BP 365
EP 372
DI 10.1038/gene.2013.27
PG 8
WC Genetics & Heredity; Immunology
SC Genetics & Heredity; Immunology
GA 213ZR
UT WOS:000324099900003
PM 23698707
ER
PT J
AU Yu, ZS
Ren, MD
Wang, ZX
Zhang, B
Rong, YKS
Jiao, RJ
Gao, GJ
AF Yu, Zhongsheng
Ren, Mengda
Wang, Zhanxiang
Zhang, Bo
Rong, Yikang S.
Jiao, Renjie
Gao, Guanjun
TI Highly Efficient Genome Modifications Mediated by CRISPR/Cas9 in
Drosophila
SO GENETICS
LA English
DT Article
ID GUIDED CAS9 NUCLEASE; GENE; MELANOGASTER; TALEN
AB We report that Cas9/gRNA mediates efficient genetic modifications in Drosophila. Through targeting seven loci, we achieved a germline efficiency of up to 100%. Genes in both heterochromatin and euchromatin can be modified efficiently. Thus the Cas9/gRNA system is an attractive tool for rapid disruption of essentially any gene in Drosophila.
C1 [Yu, Zhongsheng; Jiao, Renjie] Chinese Acad Sci, Inst Biophys, State Key Lab Brain & Cognit Sci, Beijing 100101, Peoples R China.
[Ren, Mengda; Gao, Guanjun] Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China.
[Wang, Zhanxiang; Zhang, Bo] Peking Univ, Coll Life Sci, Minist Educ, Key Lab Cell Proliferat & Differentiat, Beijing 100871, Peoples R China.
[Yu, Zhongsheng] Univ Chinese Acad Sci, Beijing 100080, Peoples R China.
[Rong, Yikang S.] NCI, Lab Biochem & Mol Biol, NIH, Bethesda, MD 20892 USA.
RP Jiao, RJ (reprint author), Chinese Acad Sci, Inst Biophys, Datun Rd 15, Beijing 100101, Peoples R China.
EM rjiao@sun5.ibp.ac.cn; gaogu@mail.tsinghua.edu.cn
RI Yu, Zhongsheng/C-8764-2015; Wang, Zhanxiang/K-4162-2016
OI Yu, Zhongsheng/0000-0001-6348-5293; Wang, Zhanxiang/0000-0003-4066-1498
FU National Natural Science Foundation of China, NSFC [31171278, 31271542];
973 program [2009CB918702, 2012CB825504]; NSFC [31071087, 31271573];
National Cancer Institute
FX We thank Dr. Jingwei Xiong for providing the plasmid of pMD19-T gRNA
scaffold vector, Wei Wei and Wenyuan Li for technical assistance in DNA
sequencing and constructing the pSP6-2sNLS-spcas9 plasmid, and Dr. Hui
Wang for providing the bacterium strain of S. pyogenes that contains the
Cas9 gene. This work was supported by the grants from the National
Natural Science Foundation of China, NSFC (31171278, 31271542). R.J. is
supported by the grants from the 973 program (2009CB918702 and
2012CB825504) and the NSFC (31071087 and 31271573). Research in Y.S.R.'s
laboratory is supported by the intramural program of National Cancer
Institute.
NR 14
TC 122
Z9 137
U1 8
U2 114
PU GENETICS SOC AM
PI BETHESDA
PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
SN 1943-2631
J9 GENETICS
JI Genetics
PD SEP
PY 2013
VL 195
IS 1
BP 289
EP +
DI 10.1534/genetics.113.153825
PG 17
WC Genetics & Heredity
SC Genetics & Heredity
GA 214YC
UT WOS:000324174200024
PM 23833182
ER
PT J
AU Fu, R
Wassif, CA
Yanjanin, NM
Watkins-Chow, DE
Baxter, LL
Incao, A
Liscum, L
Sidhu, R
Firnkes, S
Graham, M
Ory, DS
Porter, FD
Pavan, WJ
AF Fu, Rao
Wassif, Christopher A.
Yanjanin, Nicole M.
Watkins-Chow, Dawn E.
Baxter, Laura L.
Incao, Art
Liscum, Laura
Sidhu, Rohini
Firnkes, Sally
Graham, Mark
Ory, Daniel S.
Porter, Forbes D.
Pavan, William J.
TI Efficacy of N-acetylcysteine in phenotypic suppression of mouse models
of NiemannPick disease, type C1
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID LIPID STORAGE DISORDER; PICK-DISEASE; OXIDATIVE STRESS; CHOLESTEROL
HOMEOSTASIS; NEURONAL CHOLESTEROL; LYSOSOMAL CALCIUM; MURINE MODEL;
EVERY ORGAN; BALB/C MICE; NPC1
AB NiemannPick disease, type C1 (NPC1), which arises from a mutation in the NPC1 gene, is characterized by abnormal cellular storage and transport of cholesterol and other lipids that leads to hepatic disease and progressive neurological impairment. Oxidative stress has been hypothesized to contribute to the NPC1 disease pathological cascade. To determine whether treatments reducing oxidative stress could alleviate NPC1 disease phenotypes, the in vivo effects of the antioxidant N-acetylcysteine (NAC) on two mouse models for NPC1 disease were studied. NAC was able to partially suppress phenotypes in both antisense-induced (NPC1ASO) and germline (Npc1/) knockout genetic mouse models, confirming the presence of an oxidative stress-related mechanism in progression of NPC1 phenotypes and suggesting NAC as a potential molecule for treatment. Gene expression analyses of NAC-treated NPC1ASO mice suggested NAC affects pathways distinct from those initially altered by Npc1 knockdown, data consistent with NAC achieving partial disease phenotype suppression. In a therapeutic trial of short-term NAC administration to NPC1 patients, no significant effects on oxidative stress in these patients were identified other than moderate improvement of the fraction of reduced CoQ10, suggesting limited efficacy of NAC monotherapy. However, the mouse model data suggest that the distinct antioxidant effects of NAC could provide potential treatment of NPC1 disease, possibly in concert with other therapeutic molecules at earlier stages of disease progression. These data also validated the NPC1ASO mouse as an efficient model for candidate NPC1 drug screening, and demonstrated similarities in hepatic phenotypes and genome-wide transcript expression patterns between the NPC1ASO and Npc1/ models.
C1 [Fu, Rao; Wassif, Christopher A.; Yanjanin, Nicole M.; Porter, Forbes D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dept Hlth & Human Serv, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
[Watkins-Chow, Dawn E.; Baxter, Laura L.; Incao, Art; Pavan, William J.] NHGRI, Dept Hlth & Human Serv, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Liscum, Laura] Tufts Univ, Dept Physiol, Sch Med, Boston, MA 02111 USA.
[Sidhu, Rohini; Firnkes, Sally; Ory, Daniel S.] Washington Univ, Sch Med, Diabet Cardiovasc Dis Ctr, St Louis, MO 63110 USA.
[Graham, Mark] Isis Pharmaceut Inc, Cardiovasc Grp, Dept Antisense Drug Discovery, Carlsbad, CA 92008 USA.
RP Pavan, WJ (reprint author), NHGRI, Dept Hlth & Human Serv, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
EM bpavan@mail.nih.gov
RI Sidhu, Rohini/G-3547-2012;
OI Wassif, Christopher/0000-0002-2524-1420; Watkins-Chow,
Dawn/0000-0002-4355-0868
FU National Human Genome Research Institute, National Institutes of Health;
Dana's Angels Research Trust; Eunice Kennedy Shriver National Institute
of Child Health and Human Development; Ara Parseghian Medical Research
Foundation; Office of Rare Diseases; National Institutes of Health
Clinical Center
FX This work was supported by the intramural research program of the
National Human Genome Research Institute, National Institutes of Health
(W.J.P., A. I., D. E. W-C., L. L. B.); Dana's Angels Research Trust
(D.S.O, R. S., S. F.); the intramural research program of the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(F. D. P, C. A. W., N.M.Y.); the Ara Parseghian Medical Research
Foundation (D.O., F. D. P., N.M.Y.); and a Bench to Bedside award from
the Office of Rare Diseases and the National Institutes of Health
Clinical Center.
NR 63
TC 10
Z9 10
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD SEP 1
PY 2013
VL 22
IS 17
BP 3508
EP 3523
DI 10.1093/hmg/ddt206
PG 16
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 198KK
UT WOS:000322921400010
PM 23666527
ER
PT J
AU Graff, M
Ngwa, JS
Workalemahu, T
Homuth, G
Schipf, S
Teumer, A
Volzke, H
Wallaschofski, H
Abecasis, GR
Edward, L
Francesco, C
Sanna, S
Scheet, P
Schlessinger, D
Sidore, C
Xiao, XJ
Wang, ZM
Chanock, SJ
Jacobs, KB
Hayes, RB
Hu, F
Van Dam, RM
Crout, RJ
Marazita, ML
Shaffer, JR
Atwood, LD
Fox, CS
Heard-Costa, NL
White, C
Choh, AC
Czerwinski, SA
Demerath, EW
Dyer, TD
Towne, B
Amin, N
Oostra, BA
Van Duijn, CM
Zillikens, MC
Esko, T
Nelis, M
Nikopensius, T
Metspalu, A
Strachan, DP
Monda, K
Qi, L
North, KE
Cupples, LA
Gordon-Larsen, P
Berndt, SI
AF Graff, Mariaelisa
Ngwa, Julius S.
Workalemahu, Tsegaselassie
Homuth, Georg
Schipf, Sabine
Teumer, Alexander
Voelzke, Henry
Wallaschofski, Henri
Abecasis, Goncalo R.
Edward, Lakatta
Francesco, Cucca
Sanna, Serena
Scheet, Paul
Schlessinger, David
Sidore, Carlo
Xiao, Xiangjun
Wang, Zhaoming
Chanock, Stephen J.
Jacobs, Kevin B.
Hayes, Richard B.
Hu, Frank
Van Dam, Rob M.
Crout, Richard J.
Marazita, Mary L.
Shaffer, John R.
Atwood, Larry D.
Fox, Caroline S.
Heard-Costa, Nancy L.
White, Charles
Choh, Audrey C.
Czerwinski, Stefan A.
Demerath, Ellen W.
Dyer, Thomas D.
Towne, Bradford
Amin, Najaf
Oostra, Ben A.
Van Duijn, Cornelia M.
Zillikens, M. Carola
Esko, Tonu
Nelis, Mari
Nikopensius, Tit
Metspalu, Andres
Strachan, David P.
Monda, Keri
Qi, Lu
North, Kari E.
Cupples, L. Adrienne
Gordon-Larsen, Penny
Berndt, Sonja I.
CA GIANT Consortium
TI Genome-wide analysis of BMI in adolescents and young adults reveals
additional insight into the effects of genetic loci over the life course
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID BODY-MASS INDEX; CHILDHOOD OBESITY; COMMON VARIANTS; EARLY-ONSET; FAT
MASS; ASSOCIATION; RISK; FTO; WEIGHT; SH2B1
AB Genetic loci for body mass index (BMI) in adolescence and young adulthood, a period of high risk for weight gain, are understudied, yet may yield important insight into the etiology of obesity and early intervention. To identify novel genetic loci and examine the influence of known loci on BMI during this critical time period in late adolescence and early adulthood, we performed a two-stage meta-analysis using 14 genome-wide association studies in populations of European ancestry with data on BMI between ages 16 and 25 in up to 29 880 individuals. We identified seven independent loci (P 5.0 10(8)) near FTO (P 3.72 10(23)), TMEM18 (P 3.24 10(17)), MC4R (P 4.41 10(17)), TNNI3K (P 4.32 10(11)), SEC16B (P 6.24 10(9)), GNPDA2 (P 1.11 10(8)) and POMC (P 4.94 10(8)) as well as a potential secondary signal at the POMC locus (rs2118404, P 2.4 10(5) after conditioning on the established single-nucleotide polymorphism at this locus) in adolescents and young adults. To evaluate the impact of the established genetic loci on BMI at these young ages, we examined differences between the effect sizes of 32 published BMI loci in European adult populations (aged 1890) and those observed in our adolescent and young adult meta-analysis. Four loci (near PRKD1, TNNI3K, SEC16B and CADM2) had larger effects and one locus (near SH2B1) had a smaller effect on BMI during adolescence and young adulthood compared with older adults (P 0.05). These results suggest that genetic loci for BMI can vary in their effects across the life course, underlying the importance of evaluating BMI at different ages.
C1 [Graff, Mariaelisa; Monda, Keri; North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Graff, Mariaelisa; Gordon-Larsen, Penny] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA.
[Ngwa, Julius S.; White, Charles; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Workalemahu, Tsegaselassie; Hu, Frank; Van Dam, Rob M.; Qi, Lu] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Homuth, Georg; Teumer, Alexander] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany.
[Schipf, Sabine; Voelzke, Henry] Univ Med Greifswald, Inst Community Med, Greifswald, Germany.
[Wallaschofski, Henri] Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany.
[Abecasis, Goncalo R.; Sidore, Carlo] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Edward, Lakatta; Schlessinger, David; Sidore, Carlo] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
[Francesco, Cucca; Sanna, Serena] CNR, Ist Ric Genet & Biomed, Cagliari, Italy.
[Scheet, Paul; Xiao, Xiangjun] Univ Texas MD Anderson, Dept Epidemiol, Houston, TX USA.
[GIANT Consortium] GIANT, Bethesda, MD USA.
[Wang, Zhaoming; Chanock, Stephen J.; Jacobs, Kevin B.; Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Wang, Zhaoming; Jacobs, Kevin B.] NCI Frederick, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Hayes, Richard B.] NYU Med Ctr, New York, NY 10016 USA.
[Hu, Frank] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Hu, Frank] Harvard Univ, Sch Med, Boston, MA USA.
[Van Dam, Rob M.] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore.
[Van Dam, Rob M.] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore 117595, Singapore.
[Crout, Richard J.] W Virginia Univ, Dept Periodont, Morgantown, WV 26506 USA.
[Marazita, Mary L.] Univ Pittsburgh, Dept Oral Biol, Ctr Craniofacial & Dent Genet, Pittsburgh, PA USA.
[Shaffer, John R.] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA.
[Atwood, Larry D.; Fox, Caroline S.; Heard-Costa, Nancy L.] NHLBIs Framingham Heart Study, Framingham, MA USA.
[Ngwa, Julius S.; Atwood, Larry D.; Heard-Costa, Nancy L.; Cupples, L. Adrienne] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Choh, Audrey C.; Czerwinski, Stefan A.; Towne, Bradford] Wright State Univ, Sch Med, Dayton, OH USA.
[Demerath, Ellen W.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA.
[Dyer, Thomas D.] Texas Biomed Res Inst, Dept Genet, Houston, TX USA.
[Amin, Najaf; Oostra, Ben A.; Van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Zillikens, M. Carola] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Van Duijn, Cornelia M.] Ctr Med Syst Biol, Leiden, Netherlands.
[Esko, Tonu; Nelis, Mari; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.
[Esko, Tonu; Nikopensius, Tit; Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia.
[Esko, Tonu; Nelis, Mari; Metspalu, Andres] Estonian Bioctr, Tartu, Estonia.
[Nelis, Mari] Univ Geneva, Sch Med, Dept Med Genet & Dev, CH-1211 Geneva, Switzerland.
[Strachan, David P.] St Georges Univ London, Div Populat Hlth Sci & Educ, London, England.
[Monda, Keri] Amgen Inc, Ctr Observat Res, Thousand Oaks, CA 91320 USA.
[North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA.
[Gordon-Larsen, Penny] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA.
RP Graff, M (reprint author), Univ N Carolina, Dept Epidemiol, Bank Amer Ctr, 137 East Franklin Str,Suite 306, Chapel Hill, NC 27517 USA.
EM migraff@email.unc.edu
RI van Dam, Rob/F-9674-2010;
OI van Dam, Rob/0000-0002-7354-8734; Heard-Costa,
Nancy/0000-0001-9730-0306; Cupples, L. Adrienne/0000-0003-0273-7965;
Sidore, Carlo/0000-0001-7504-7477; sanna, serena/0000-0002-3768-1749;
Esko, Tonu/0000-0003-1982-6569; Hayes, Richard/0000-0002-0918-661X
FU National Institutes of Health [R01HD057194, HHSN268200625226C,
R01-HD012252, R01-HD053685, R01-DK064391, R01-AR052147]; National Heart,
Lung, and Blood Institute [N01-HC-55015, N01-HC-55016, N01-HC-55018,
N01-HC-55019, N01-HC- 55020, N01-HC-55021, N01-HC-55022, R01HL087641,
R01HL59367, R01HL086694]; National Human Genome Research Institute
[U01HG004402]; National Center for Research Resources (NCRR) [UL1 RR
025005]; Medical Research Council [G0000934]; Wellcome Trust
[068545/Z/02, 076113/B/04/Z]; National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK); National Institute of Allergy and
Infectious Diseases (NIAID); National Human Genome Research Institute
(NHGRI); National Institute of Child Health and Human Development
(NICHD); Juvenile Diabetes Research Foundation International (JDRF);
EUROSPAN (European Special Populations Research Network); European
Commission FP6 STRP [018947, LSHG-CT-2006-01947]; Netherlands
Organization for Scientific Research; Erasmus MC; Centre for Medical
Systems Biology (CMSB); Netherlands Brain Foundation (HersenStichting
Nederland); ENGAGE; OPENGENE; Estonian Government [SF0180142s08];
Estonian Research Roadmap through Estonian Ministry of Education and
Research [3.2.0304.11-0312]; Center of Excellence in Genomics (EXCEGEN);
University of Tartu [SP1GVARENG]; National Heart, Lung and Blood
Institute's Framingham Heart Study [N01-HC-25195]; Affymetrix, Inc.
[N02-HL-6-4278]; Department of Medicine at Boston University School of
Medicine; Boston Medical Center; NIH [R01HD057194]; National Institutes
of Dental and Craniofacial Research [U01-DE018903]; NIDCR [R01-DE
014899]; National Institutes of Health (NIH) [HHSN268200782096C]; NIDCR
through CIDR's NIH; National Institutes of Health (Boston Obesity
Nutrition Research Center) [HL71981, DK46200]; American Heart
Association [0730094N]; Division of Cancer Epidemiology and Genetics,
National Cancer Institute, NIH; Federal Ministry of Education and
Research [01ZZ9603, 01ZZ0103, 01ZZ0403, 03IS2061A, 03ZIK012]; Ministry
of Cultural Affairs; Social Ministry of the Federal State of
Mecklenburg-West Pomerania; Siemens Healthcare, Erlangen, Germany;
Federal State of Mecklenburg-West Pomerania; National Institute on Aging
(NIA) and National Institutes of Health (NIH) [NO1-AG-1-2109]; [U01
DK062418]
FX This work was funded by National Institutes of Health (R01HD057194).;
Atherosclerosis Risk in Communities (ARIC). The Atherosclerosis Risk in
Communities Study is carried out as a collaborative study supported by
National Heart, Lung, and Blood Institute (N01-HC-55015, N01-HC-55016,
N01-HC-55018, N01-HC-55019, N01-HC- 55020, N01-HC-55021, N01-HC-55022,
R01HL087641, R01HL59367 and R01HL086694); National Human Genome Research
Institute (U01HG004402); and National Institutes of Health
(HHSN268200625226C). Infrastructure was partly supported by a component
of the National Institutes of Health and NIH Roadmap for Medical
Research (UL1RR025005). The project described was supported by the
National Center for Research Resources (NCRR) (UL1 RR 025005).; British
1958 Birth Cohort (B58C). We acknowledge the use of phenotype and
genotype data from the British 1958 Birth Cohort DNA collection, funded
by the Medical Research Council (G0000934) and the Wellcome Trust
(068545/Z/02) (http://www.b58cgene.sgul.ac.uk/). Genotyping for the
B58C-WTCCC subset was funded by the Wellcome Trust (076113/B/04/Z). The
B58C-T1DGC genotyping utilized resources provided by the Type 1 Diabetes
Genetics Consortium, a collaborative study sponsored by the National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK),
National Institute of Allergy and Infectious Diseases (NIAID), National
Human Genome Research Institute (NHGRI), National Institute of Child
Health and Human Development (NICHD), and Juvenile Diabetes Research
Foundation International (JDRF) and supported by U01 DK062418.; Erasmus
Rucphen Family (EUROSPAN) (ERF). The genotyping for the ERF study was
supported by EUROSPAN (European Special Populations Research Network)
and the European Commission FP6 STRP (018947; LSHG-CT-2006-01947). The
ERF study was further supported by grants from the Netherlands
Organization for Scientific Research, Erasmus MC, the Centre for Medical
Systems Biology (CMSB) and the Netherlands Brain Foundation
(HersenStichting Nederland).; Estonian Genome Center, University of
Tartu (EGCUT). EGCUT received financing by (ENGAGE, OPENGENE), targeted
financing from Estonian Government (funding no: SF0180142s08), Estonian
Research Roadmap through Estonian Ministry of Education and Research
(3.2.0304.11-0312), Center of Excellence in Genomics (EXCEGEN) and
Development Fund of University of Tartu (funding no: SP1GVARENG).;
Framingham Heart Study (FramHS). This research was partially supported
by the National Heart, Lung and Blood Institute's Framingham Heart Study
(contract no: N01-HC-25195) and its contract with Affymetrix, Inc., for
genotyping services (contract no. N02-HL-6-4278). A portion of this
research utilized the Linux Cluster for Genetic Analysis (LinGA-II)
funded by the Robert Dawson Evans Endowment of the Department of
Medicine at Boston University School of Medicine and Boston Medical
Center. Analyses of the Framingham data were supported by subcontract to
Boston University under NIH (R01HD057194).; Dental Caries: Whole Genome
Association and Gene x Environment Studies (GENEVA Dental Caries).
Funding support for the GWAS project was provided by the National
Institutes of Dental and Craniofacial Research (U01-DE018903). Data and
samples were provided by the Center for Oral Health Research in
Appalachia, a collaboration of the University of Pittsburgh and West
Virginia University funded by NIDCR (R01-DE 014899); genotyping was done
by the Johns Hopkins University Center for Inherited Disease Research
(CIDR) which is fully funded through a federal contract from the
National Institutes of Health (NIH) to The Johns Hopkins University
(contract no: HHSN268200782096C). Funds for this project's genotyping
were provided by the NIDCR through CIDR's NIH contract. Assistance with
phenotype harmonization and genotype cleaning, as well as with general
study coordination, was provided by the GENEVA Coordinating Center
(www.genevastudy.org; U01-HG004446).; Fels Longitudinal Study (Fels).
This work was supported by the National Institutes of Health
(R01-HD012252, R01-HD053685, R01-DK064391, R01-AR052147).; The Nurses'
Health Study/Health Professionals Follow up Study (NHS/HPFS). This study
was supported by National Institutes of Health grants [HL71981 and
DK46200 (Boston Obesity Nutrition Research Center)] and by an American
Heart Association Scientist Development Award (0730094N).; Prostate,
Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO/PLCO2). The
Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial
was funded by the Intramural Research Program of the Division of Cancer
Epidemiology and Genetics, National Cancer Institute, NIH.; Study of
Health in Pomerania (SHIP). SHIP is part of the Community Medicine
Research net of the University of Greifswald, Germany, which is funded
by the Federal Ministry of Education and Research (01ZZ9603, 01ZZ0103
and 01ZZ0403), the Ministry of Cultural Affairs as well as the Social
Ministry of the Federal State of Mecklenburg-West Pomerania, and the
network 'Greifswald Approach to Individualized Medicine (GANI_MED)'
funded by the Federal Ministry of Education and Research (03IS2061A).
Genome-wide data have been supported by the Federal Ministry of
Education and Research (03ZIK012) and a joint grant from Siemens
Healthcare, Erlangen, Germany, and the Federal State of Mecklenburg-West
Pomerania.; Study of Health in Sardinia, Italy (SardNIA). This work was
supported in part by the Intramural Research Program of the National
Institute on Aging (NIA) and National Institutes of Health (NIH)
(NO1-AG-1-2109).
NR 40
TC 42
Z9 45
U1 1
U2 16
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 SEP 1
PY 2013
VL 22
IS 17
BP 3597
EP 3607
DI 10.1093/hmg/ddt205
PG 11
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 198KK
UT WOS:000322921400017
PM 23669352
ER
PT J
AU Sebastiano, C
Zhao, XR
Deng, FM
Das, K
AF Sebastiano, Christopher
Zhao, Xiangrong
Deng, Fang-Ming
Das, Kasturi
TI Cystic lesions of the adrenal gland: our experience over the last 20
years
SO HUMAN PATHOLOGY
LA English
DT Article
DE Adrenal cyst; Pseudocyst; Endothelial cyst; Epithelial cyst;
Radiopathologic correlation
ID OF-THE-LITERATURE; PSEUDOCYSTS; MANAGEMENT; VARIANTS; PATIENT
AB Cystic lesions of the adrenal gland are uncommon, often presenting with nonspecific clinical and radiologic findings, and are thus underrecognized. They are occasionally associated with malignant neoplasms, which can greatly mimic benign lesions and carry detrimental clinical consequences if misdiagnosed. Here we present our 20-year experience (1992-2012) with these lesions at an academic medical center. Among more than 4500 adrenal gland specimens, 31 cases of adrenal lesions with a predominant cystic component were identified in 30 patients with an age range of 34 to 86 years (median, 55.5 years) and a male/female ratio of 13:17. Macroscopic descriptions, available histologic and immunostain slides, and available radiologic records were reviewed for all included cases. Radiologic studies and gross examination correlated well, and hemorrhage (26 cases; 84%) and encapsulation (25 cases; 81%) appeared to be nonspecific radiologic/gross features shared across histologic subtypes. Microscopic review identified 12 cases (39%) of pseudocysts, 2 cases (6%) of endothelium-derived cysts, and 17 cases (55%) of epithelium-derived cysts. Among these 31 cystic adrenal lesions, 2 cases (6%) were malignant neoplasms (1 epithelioid angiosarcoma, 1 adrenocortical carcinoma). Radiologic impression and histopathologic diagnosis were concordant in 11 (73%) of the 15 cases for which radiologic records were available. This study represents the second largest case series to date on cystic adrenal lesions and presents a comprehensive review on their demographic, clinical, radiologic, and gross and microscopic pathologic features, as well as their differential diagnoses. Published by Elsevier Inc.
C1 [Sebastiano, Christopher; Zhao, Xiangrong; Deng, Fang-Ming; Das, Kasturi] NYU, Langone Med Ctr, Dept Pathol, New York, NY 10016 USA.
RP Zhao, XR (reprint author), NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM xiangrong.zhao@nih.gov
NR 29
TC 6
Z9 6
U1 0
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0046-8177
J9 HUM PATHOL
JI Hum. Pathol.
PD SEP
PY 2013
VL 44
IS 9
BP 1797
EP 1803
DI 10.1016/j.humpath.2013.02.002
PG 7
WC Pathology
SC Pathology
GA 214RF
UT WOS:000324152500013
PM 23618356
ER
PT J
AU Smith, CE
Ngwa, J
Tanaka, T
Qi, Q
Wojczynski, MK
Lemaitre, RN
Anderson, JS
Manichaikul, A
Mikkila, V
Van Rooij, FJA
Ye, Z
Bandinelli, S
Frazier-Wood, AC
Houston, DK
Hu, F
Langenberg, C
McKeown, NM
Mozaffarian, D
North, KE
Viikari, J
Zillikens, MC
Djousse, L
Hofman, A
Kahonen, M
Kabagambe, EK
Loos, RJF
Saylor, GB
Forouhi, NG
Liu, Y
Mukamal, KJ
Chen, YDI
Tsai, MY
Uitterlinden, AG
Raitakari, O
Van Duijn, CM
Arnett, DK
Borecki, IB
Cupples, LA
Ferrucci, L
Kritchevsky, SB
Lehtimaki, T
Qi, L
Rotter, JI
Siscovick, DS
Wareham, NJ
Witteman, JCM
Ordovas, JM
Nettleton, JA
AF Smith, C. E.
Ngwa, J.
Tanaka, T.
Qi, Q.
Wojczynski, M. K.
Lemaitre, R. N.
Anderson, J. S.
Manichaikul, A.
Mikkila, V.
Van Rooij, F. J. A.
Ye, Z.
Bandinelli, S.
Frazier-Wood, A. C.
Houston, D. K.
Hu, F.
Langenberg, C.
McKeown, N. M.
Mozaffarian, D.
North, K. E.
Viikari, J.
Zillikens, M. C.
Djousse, L.
Hofman, A.
Kahonen, M.
Kabagambe, E. K.
Loos, R. J. F.
Saylor, G. B.
Forouhi, N. G.
Liu, Y.
Mukamal, K. J.
Chen, Y-D I.
Tsai, M. Y.
Uitterlinden, A. G.
Raitakari, O.
Van Duijn, C. M.
Arnett, D. K.
Borecki, I. B.
Cupples, L. A.
Ferrucci, L.
Kritchevsky, S. B.
Lehtimaki, T.
Qi, Lu
Rotter, J. I.
Siscovick, D. S.
Wareham, N. J.
Witteman, J. C. M.
Ordovas, J. M.
Nettleton, J. A.
TI Lipoprotein receptor-related protein 1 variants and dietary fatty acids:
meta-analysis of European origin and African American studies
SO INTERNATIONAL JOURNAL OF OBESITY
LA English
DT Article
DE low-density lipoprotein receptor-related protein 1; SNPs; saturated
fatty acids; gene-diet interactions
ID GENE-ENVIRONMENT INTERACTIONS; OBESITY-ASSOCIATED GENE; WEIGHT-LOSS
DIETS; ADIPOSE-TISSUE; BODY-WEIGHT; ASSOCIATION; MASS; EXPRESSION;
COHORT; SAMPLE
AB OBJECTIVE: Low-density lipoprotein-related receptor protein 1 (LRP1) is a multi-functional endocytic receptor and signaling molecule that is expressed in adipose and the hypothalamus. Evidence for a role of LRP1 in adiposity is accumulating from animal and in vitro models, but data from human studies are limited. The study objectives were to evaluate (i) relationships between LRP1 genotype and anthropometric traits, and (ii) whether these relationships were modified by dietary fatty acids.
DESIGN AND METHODS: We conducted race/ethnic-specific meta-analyses using data from 14 studies of US and European whites and 4 of African Americans to evaluate associations of dietary fatty acids and LRP1 genotypes with body mass index (BMI), waist circumference and hip circumference, as well as interactions between dietary fatty acids and LRP1 genotypes. Seven single-nucleotide polymorphisms (SNPs) of LRP1 were evaluated in whites (N up to 42 000) and twelve SNPs in African Americans (N up to 5800).
RESULTS: After adjustment for age, sex and population substructure if relevant, for each one unit greater intake of percentage of energy from saturated fat (SFA), BMI was 0.104 kg m(-2) greater, waist was 0.305 cm larger and hip was 0.168 cm larger (all P<0.0001). Other fatty acids were not associated with outcomes. The association of SFA with outcomes varied by genotype at rs2306692 (genotyped in four studies of whites), where the magnitude of the association of SFA intake with each outcome was greater per additional copy of the T allele: 0.107 kg m(-2) greater for BMI (interaction P - 0.0001), 0.267 cm for waist (interaction P = 0.001) and 0.21 cm for hip (interaction P = 0.001). No other significant interactions were observed.
CONCLUSION: Dietary SFA and LRP1 genotype may interactively influence anthropometric traits. Further exploration of this, and other diet x genotype interactions, may improve understanding of interindividual variability in the relationships of dietary factors with anthropometric traits.
C1 [Smith, C. E.; McKeown, N. M.; Ordovas, J. M.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Nutr & Genom Lab, Boston, MA 02111 USA.
[Ngwa, J.; Cupples, L. A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Tanaka, T.; Ferrucci, L.] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Qi, Q.; Hu, F.; Qi, Lu] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Wojczynski, M. K.; Borecki, I. B.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
[Lemaitre, R. N.] Univ Washington, Dept Med, Seattle, WA USA.
[Anderson, J. S.; Saylor, G. B.] Wake Forest Sch Med, Cardiol Sect, Dept Internal Med, Winston Salem, NC USA.
[Manichaikul, A.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
[Manichaikul, A.] Univ Virginia, Div Biostat & Epidemiol, Charlottesville, VA USA.
[Mikkila, V.] Univ Helsinki, Dept Food & Environm Sci, Helsinki, Finland.
[Van Rooij, F. J. A.; Hofman, A.; Uitterlinden, A. G.; Van Duijn, C. M.; Witteman, J. C. M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Van Rooij, F. J. A.; Zillikens, M. C.; Hofman, A.; Uitterlinden, A. G.; Van Duijn, C. M.; Witteman, J. C. M.] NGI, NCHA, Leiden, Netherlands.
[Ye, Z.; Langenberg, C.; Loos, R. J. F.; Forouhi, N. G.; Wareham, N. J.] Addenbrookes Hosp, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
[Bandinelli, S.] Azienda Sanitaria Firenze, Geriatr Rehabil Unit, Florence, Italy.
[Frazier-Wood, A. C.; Kabagambe, E. K.; Arnett, D. K.] Univ Alabama Birmingham, Sect Stat Genet, Dept Epidemiol, Birmingham, AL USA.
[Frazier-Wood, A. C.; Kabagambe, E. K.; Arnett, D. K.] Univ Alabama Birmingham, Off Energet, Birmingham, AL USA.
[Houston, D. K.; Kritchevsky, S. B.] Wake Forest Univ, Sch Med, Sticht Ctr Aging, Winston Salem, NC 27109 USA.
[Hu, F.; Qi, Lu] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Hu, F.; Qi, Lu] Harvard Univ, Sch Med, Boston, MA USA.
[Mozaffarian, D.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Mozaffarian, D.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Mozaffarian, D.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA.
[Mozaffarian, D.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA.
[Mozaffarian, D.] Harvard Univ, Sch Med, Boston, MA USA.
[North, K. E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[North, K. E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA.
[Viikari, J.] Univ Turku, Dept Med, Turku, Finland.
[Viikari, J.] Turku Univ Hosp, FIN-20520 Turku, Finland.
[Zillikens, M. C.; Uitterlinden, A. G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Djousse, L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA.
[Djousse, L.] Boston VA Healthcare Syst, Boston, MA USA.
[Kahonen, M.] Univ Tampere, Dept Clin Physiol, FIN-33101 Tampere, Finland.
[Kahonen, M.] Tampere Univ Hosp, Tampere, Finland.
[Liu, Y.] Wake Forest Univ, Bowman Gray Sch Med, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC USA.
[Mukamal, K. J.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA.
[Chen, Y-D I.; Rotter, J. I.] Cedars Sinai Med Ctr, Med Genet Res Inst, Los Angeles, CA 90048 USA.
[Tsai, M. Y.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
[Raitakari, O.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.
[Raitakari, O.] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, FIN-20520 Turku, Finland.
[Cupples, L. A.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Lehtimaki, T.] Univ Tampere, Fimlab Labs, Dept Clin Chem, FIN-33101 Tampere, Finland.
[Lehtimaki, T.] Tampere Univ Hosp, Tampere, Finland.
[Siscovick, D. S.] Univ Washington, Dept Med, Seattle, WA USA.
[Siscovick, D. S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Ordovas, J. M.] CNIC, Dept Epidemiol & Populat Genet, Madrid, Spain.
[Ordovas, J. M.] Estudios Avanzados Alimentac, Inst Madrilenos, Madrid, Spain.
[Nettleton, J. A.] Univ Texas Hlth Sci Ctr Houston, Div Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA.
RP Ordovas, JM (reprint author), Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Nutr & Genom Lab, 711 Washington St, Boston, MA 02111 USA.
EM jose.ordovas@tufts.edu
RI Djousse, Luc/F-5033-2017; Wood, Lekki/B-8053-2010;
OI Djousse, Luc/0000-0002-9902-3047; Wood, Lekki/0000-0001-7616-2119;
Forouhi, Nita/0000-0002-5041-248X
FU National Heart, Lung and Blood Institute [HHSN268 201100005C,
HHSN268201100006C, HHSN268201100007C, HHSN268201100008C,
HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268
201100012C]; National Human Genome Research Institute [U01HG004402];
National Institutes of Health [HHSN268200625226C, UL1RR025005,
HHSN268200782096C, HL71981, CA055075, CA87969, CA49449]; NIH Roadmap for
Medical Research; National Institutes of Health, National Institute of
Diabetes and Digestive and Kidney Diseases [5K01DK 082729-04]; NHLBI
[N01-HC-85239, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082,
N01-HC-85083, N01-HC-85084, N01-HC-85085, N01-HC-85086, N01-HC-35129];
NIA [AG-023629, AG-15928, AG-20098, AG-027058, R01 AG032098]; National
Center of Advancing Translational Technologies CTSI [UL1TR000124];
National Institute of Diabetes and Digestive and Kidney Diseases
[DK063491]; Medical Research Council; Cancer Research United Kingdom;
Stroke Association; British Heart Foundation; Research Into Ageing;
Academy of Medical Science; NIH from NHLBI [R01 HL087700, R01 HL088215];
NIDDK [R01 DK075681, R01 DK8925601]; Wellcome Trust; Affymetrix, Inc.
[N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of
Medicine at Boston University School of Medicine; Boston Medical Center;
NIH/NIDDK [R01 DK089256-01]; USDA [58-1950-7-707]; US Department of
Agriculture Research Service [53-K06-5-10, 58-1950-9-001]; Intramural
Research Program of the NIH, National Institute on Aging [N01AG62101,
N01AG62103, N01AG62106]; American Heart Association [0730094N]; Italian
Ministry of Health; US National Institute on Aging [263 MD 9164, 263 MD
821336]; National Heart, Lung and Blood Institute (NHLBI) [N01-HC-95159,
N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164,
N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169,
RR-024156]; Netherlands Organisation of Scientific Research NWO
Investments [175.010.2005.011, 911-03-012]; Research Institute for
Diseases in the Elderly [014-93-015]; Netherlands Genomics Initiative
(NGI)/Netherlands Organisation for Scientific Research (NWO)
[050-060-810]; Erasmus Medical Center; 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; Municipality of Rotterdam; Academy of
Finland [126925, 121584, 124282, 129378, 117787, 41071]; Social
Insurance Institution of Finland, Kuopio, Tampere; Turku University
Hospital Medical Funds [9M048, 9N035]; Juho Vainio Foundation; Paavo
Nurmi Foundation; Finnish Foundation of Cardiovascular Research; Finnish
Cultural Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen
Foundation; NHLBI. [N02-HL-6-4278, N01 HC-15103, N01 HC-55222,
N01-HC-75150, N01-HC-45133, HHSN268201200036C, HL080295, R01-HL085251,
HL087652, HL105756, N01-HC-25195, U01-HL072524]; [R01HL087641];
[R01HL59367]; [R01HL086694]; [P50 HL105185-01]; [ICS110.1/RF97.71];
[R01HL071051]; [R01HL071205]; [R01HL071250]; [R01HL071251];
[R01HL071252]; [R01HL 071258]; [R01HL071259]
FX The Atherosclerosis Risk In Communities (ARIC) Study is carried out as a
collaborative study supported by National Heart, Lung and Blood
Institute contracts (HHSN268 201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C and HHSN268 201100012C),
R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research
Institute contract U01HG004402; and National Institutes of Health
contract HHSN268200625226C. We the staff and participants of the ARIC
study for their important contributions. Infrastructure was partly
supported by Grant Number UL1RR025005, a component of the National
Institutes of Health and NIH Roadmap for Medical Research. Dr Nettleton
is supported by a K01 from the National Institutes of Health, National
Institute of Diabetes and Digestive and Kidney Diseases (5K01DK
082729-04). Cardiovascular Health Study (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, R01-HL085251 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.htm. DNA handling and
genotyping was supported in part by National Center of Advancing
Translational Technologies CTSI grant UL1TR000124 and National Institute
of Diabetes and Digestive and Kidney Diseases grant DK063491 to the
Southern California Diabetes Endocrinology Research Center. European
Prospective Investigation of Cancer Norfolk (EPIC Norfolk): EPIC-Norfolk
is supported by grant funding from the Medical Research Council and
Cancer Research United Kingdom with additional support from the Stroke
Association, British Heart Foundation, Research Into Ageing and the
Academy of Medical Science. The Family Heart Study (FamHS) work was
supported by NIH grants R01 HL087700, R01 HL088215 (Michael A. Province)
from NHLBI; and R01 DK075681 and R01 DK8925601 from NIDDK (Ingrid B.
Borecki). The investigators thank the staff and participants of the
FamHS for their important contributions. The Fenland Study is funded by
the Wellcome Trust and the Medical Research Council. We are grateful to
all the volunteers for their time and help and to the General
Practitioners and practice staff for help with recruitment. We thank the
Fenland Study co-ordination team, the Field Epidemiology team and the
Fenland Study investigators. Biochemical assays were performed by the
National Institute for Health Research, Cambridge Biomedical Research
Centre, Core Biochemistry Assay Laboratory and the Cambridge University
Hospitals NHS Foundation Trust. The Framingham Offspring Study and
Framingham Third Generation Study (FHS) were conducted in part using
data and resources from the Framingham Heart Study of the National Heart
Lung and Blood Institute of the National Institutes of Health and Boston
University School of Medicine. The analyses reflect intellectual input
and resource development from the Framingham Heart Study investigators
participating in the SNP Health Association Resource (SHARe) project.
This work was partially supported by the National Heart, Lung and Blood
Institute's Framingham Heart Study (Contract No. N01-HC-25195) and its
contract with Affymetrix, Inc., for genotyping services (Contract No.
N02-HL-6-4278).; A portion of this research utilized the Linux Cluster
for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans
Endowment of the Department of Medicine at Boston University School of
Medicine and Boston Medical Center. Dr Cupples and Mr Ngwa are partially
supported by NIH/NIDDK grant R01 DK089256-01. Dr Nicola McKeown is
supported by the USDA agreement No. 58-1950-7-707. The GOLDN (Genetics
of Lipid Lowering Drugs and Diet Network) study was funded by the
National Heart, Lung and Blood Institute Grant No. U01-HL072524, Genetic
and Environmental Determinants of Triglycerides. Dr Smith and Dr Ordovas
are partially supported by P50 HL105185-01 and contracts 53-K06-5-10 and
58-1950-9-001 from the US Department of Agriculture Research Service.
The Health, Aging and Body Composition (Health ABC) study was supported
in part by the Intramural Research Program of the NIH, National
Institute on Aging contracts N01AG62101, N01AG62103 and N01AG62106. The
genome-wide association study was funded by NIA grant R01 AG032098 to
Wake Forest University Health Sciences and genotyping services were
provided by the Center for Inherited Disease Research (CIDR). CIDR is
fully funded through a federal contract from the National Institutes of
Health to The Johns Hopkins University, contract number
HHSN268200782096C. Health Professionals Follow-up Study (HPFS): The HPFS
was supported by grants HL71981 and CA055075 from the National
Institutes of Health. Dr Lu Qi is a recipient of the American Heart
Association Scientist Development Award (0730094N). We thank the
participants of the HPFS for their continued cooperation. Invecchiare in
Chianti (aging in the Chianti area, InCHIANTI) study investigators thank
the Intramural Research Program of the NIH, National Institute on Aging
who are responsible for the InCHIANTI samples. Investigators also thank
the InCHIANTI participants. The InCHIANTI study baseline (1998-2000) was
supported as a 'targeted project' (ICS110.1/RF97.71) by the Italian
Ministry of Health and in part by the US National Institute on Aging
(Contracts: 263 MD 9164 and 263 MD 821336). MESA and the MESA SHARe
project are conducted and supported by contracts N01-HC-95159 through
N01-HC-95169 and RR-024156 from the National Heart, Lung and Blood
Institute (NHLBI). Funding for MESA SHARe genotyping was provided by
NHLBI Contract N02-HL-6-4278. MESA Family is conducted and supported in
collaboration with MESA investigators; support is provided by grants and
contracts R01HL071051, R01HL071205, R01HL071250, R01HL071251,
R01HL071252, R01HL 071258, R01HL071259. We thank the participants of the
MESA study, the Coordinating Center, MESA investigators, and study staff
for their valuable contributions. A full list of participating MESA
investigators and institutions can be found at
http://www.mesa-nhlbi.org. Nurses Health Study (NHS): The NHS was
supported by grants HL71981, CA87969 and CA49449 from the National
Institutes of Health. Dr Lu Qi is a recipient of the American Heart
Association Scientist Development Award (0730094N). We thank the
participants of the NHS for their continued cooperation. Rotterdam
Study: The generation and management of GWAS genotype data for the
Rotterdam Study is supported by the Netherlands Organisation of
Scientific Research NWO Investments (nr. 175.010.2005.011, 911-03-012).
This study is funded by the Research Institute for Diseases in the
Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative
(NGI)/Netherlands Organisation for Scientific Research (NWO) project nr.
050-060-810.; We thank Pascal Arp, Mila Jhamai, Marijn Verkerk, Lizbeth
Herrera and Marjolein Peters for their help in creating the GWAS
database, and Karol Estrada and Maksim V. Struchalin for their support
in creation and analysis of imputed data. The Rotterdam Study is funded
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. We are grateful to the study participants, the staff from the
Rotterdam Study and the participating general practitioners and
pharmacists. Young Finns Study: The Young Finns Study has been
financially supported by the Academy of Finland: grants 126925, 121584,
124282, 129378 (Salve), 117787 (Gendi) and 41071 (Skidi), the Social
Insurance Institution of Finland, Kuopio, Tampere and Turku University
Hospital Medical Funds (grant 9M048 and 9N035 for TeLeht), Juho Vainio
Foundation, Paavo Nurmi Foundation, Finnish Foundation of Cardiovascular
Research and Finnish Cultural Foundation, Tampere Tuberculosis
Foundation and Emil Aaltonen Foundation (T. L). The authors gratefully
acknowledge the statistical analyses provided by Ville Aalto.
NR 39
TC 3
Z9 3
U1 0
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0307-0565
J9 INT J OBESITY
JI Int. J. Obes.
PD SEP
PY 2013
VL 37
IS 9
BP 1211
EP 1220
DI 10.1038/ijo.2012.215
PG 10
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 216QX
UT WOS:000324300100008
PM 23357958
ER
PT J
AU Bekelman, JE
Schultheiss, T
De Gonzalez, B
AF Bekelman, Justin E.
Schultheiss, Timothy
De Gonzalez, Berrington
TI Subsequent Malignancies After Photon Versus Proton Radiation Therapy
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Editorial Material
ID CHILDHOOD-CANCER SURVIVOR; 5-YEAR SURVIVORS; NEOPLASMS
C1 [Bekelman, Justin E.] Univ Penn, Dept Radiat Oncol, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Bekelman, Justin E.] Univ Penn, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Bekelman, Justin E.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA.
[Schultheiss, Timothy] City Hope Canc Ctr, Dept Radiat Oncol, Los Angeles, CA USA.
[De Gonzalez, Berrington] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Bekelman, JE (reprint author), Dept Radiat Oncol, 3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM bekelman@uphs.upenn.edu
OI Schultheiss, Timothy/0000-0002-8984-196X
FU NCI NIH HHS [1K07CA16316-01]
NR 9
TC 9
Z9 9
U1 1
U2 7
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 SEP 1
PY 2013
VL 87
IS 1
BP 10
EP 12
DI 10.1016/j.ijrobp.2013.05.016
PG 3
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 216UE
UT WOS:000324309500006
PM 23810521
ER
PT J
AU Reilly, EAO
Sharma, S
Klinger, R
Gubbins, L
Kelly, C
Lyons, T
Maguire, A
Aherne, S
Barry, M
Conlon, S
McCaffrey, J
Harrison, M
Glynn, S
McCann, A
Kell, M
AF Reilly, E. A. O.
Sharma, S.
Klinger, R.
Gubbins, L.
Kelly, C.
Lyons, T.
Maguire, A.
Aherne, S.
Barry, M.
Conlon, S.
McCaffrey, J.
Harrison, M.
Glynn, S.
McCann, A.
Kell, M.
TI Low MAD2 Protein Expression is a Predictor of Poor Outcome After
Chemotherapy & Radiotherapy in Oestrogen Receptor Negative Breast Cancer
SO IRISH JOURNAL OF MEDICAL SCIENCE
LA English
DT Meeting Abstract
C1 [Reilly, E. A. O.; Sharma, S.; Klinger, R.; Gubbins, L.; McCann, A.] UCD Sch Med & Med Sci SMMS, UCD Conway Inst Biomol & Biomed Res, Dept Pathol, Belfield, Ireland.
[Kelly, C.; Lyons, T.; McCaffrey, J.] Mater Misericordiae Univ Hosp, Dept Oncol, Dublin 1, Ireland.
[Maguire, A.; Aherne, S.] St Vincents Univ Hosp, Dept Pathol, Dublin 4, Ireland.
[Barry, M.; Kell, M.] Mater Misericordiae Univ Hosp, Dept Surg, Dublin 1, Ireland.
[Conlon, S.; Harrison, M.] Mater Misericordiae Univ Hosp, Dept Pathol, Dublin 1, Ireland.
[Glynn, S.] NCI, Dept Prostate Canc Inst, NUI Galway, Bethesda, MD 20892 USA.
RI Glynn, Sharon/D-7136-2013
OI Glynn, Sharon/0000-0003-1459-2580
NR 0
TC 0
Z9 0
U1 0
U2 4
PU SPRINGER LONDON LTD
PI LONDON
PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND
SN 0021-1265
J9 IRISH J MED SCI
JI Irish J. Med. Sci.
PD SEP
PY 2013
VL 182
SU 7
MA 37
BP S331
EP S331
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 217CX
UT WOS:000324335400038
ER
PT J
AU Ballard-Barbash, R
Krebs-Smith, SM
Neuhouser, ML
AF Ballard-Barbash, Rachel
Krebs-Smith, Susan M.
Neuhouser, Marian L.
TI Potential to Link Dietary Patterns in the Food Supply and Populations to
Health
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID EATING INDEX-2005; COLORECTAL-CANCER; RISK
C1 [Ballard-Barbash, Rachel; Krebs-Smith, Susan M.] NCI, Appl Res Program, Bethesda, MD 20892 USA.
[Neuhouser, Marian L.] Fred Hutchinson Canc Res Ctr, Prevent Ctr, Seattle, WA 98104 USA.
RP Ballard-Barbash, R (reprint author), NCI, Appl Res Program, Div Canc Control & Populat Sci, NCI Shady Grove, Rm 3E406,9609 Med Ctr Dr,MSC 9762, Bethesda, MD 20892 USA.
EM barbashr@mail.nih.gov
NR 14
TC 0
Z9 0
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 JNCI-J NATL CANCER I
JI JNCI-. Natl. Cancer Inst.
PD SEP
PY 2013
VL 105
IS 17
BP 1265
EP 1267
DI 10.1093/jnci/djt220
PG 4
WC Oncology
SC Oncology
GA 213EW
UT WOS:000324038500005
PM 23949328
ER
PT J
AU Jochmanova, I
Yang, CZ
Zhuang, ZP
Pacak, K
AF Jochmanova, Ivana
Yang, Chunzhang
Zhuang, Zhengping
Pacak, Karel
TI Hypoxia-Inducible Factor Signaling in Pheochromocytoma: Turning the
Rudder in the Right Direction
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Review
ID RENAL-CELL-CARCINOMA; ENDOCRINE NEOPLASIA TYPE-2; ENDOTHELIAL
GROWTH-FACTOR; HIPPEL-LINDAU-DISEASE; TUMOR-SUPPRESSOR PROTEIN; FACTOR
1-ALPHA HIF-1-ALPHA; SDHD GENE-MUTATIONS; KAPPA-B ACTIVITY; C-MYC;
FACTOR-I
AB Many solid tumors, including pheochromocytoma (PHEO) and paraganglioma (PGL), are characterized by a (pseudo) hypoxic signature. (Pseudo) hypoxia has been shown to promote both tumor progression and resistance to therapy. The major mediators of the transcriptional hypoxic response are hypoxia-inducible factors (HIFs). High levels of HIFs lead to transcription of hypoxia-responsive genes, which are involved in tumorigenesis. PHEOs and PGLs are catecholamine-producing tumors arising from sympathetic-or parasympathetic-derived chromaffin tissue. In recent years, substantial progress has been made in understanding the metabolic disturbances present in PHEO and PGL, especially because of the identification of some diseases-usceptibility genes. To date, fifteen PHEO and PGL susceptibility genes have been identified. Based on the main transcription signatures of the mutated genes, PHEOs and PGLs have been divided into two clusters, pseudohypoxic cluster 1 and cluster 2, rich in kinase receptor signaling and protein translation pathways. Although these two clusters seem to show distinct signaling pathways, recent data suggest that both clusters are interconnected by HIF signaling as the important driver in their tumorigenesis, and mutations in most PHEO and PGL susceptibility genes seem to affect HIF-alpha regulation and its downstream signaling pathways. HIF signaling appears to play an important role in the development and growth of PHEOs and PGLs, which could suggest new therapeutic approaches for the treatment of these tumors.
C1 [Jochmanova, Ivana; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Yang, Chunzhang; Zhuang, Zhengping] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Jochmanova, Ivana] PJ Safarik Univ Kosice, Fac Med, Dept Internal Med 1, Kosice, Slovakia.
RP Pacak, K (reprint author), Eunice Kennedy Shriver NICHD, Sect Med Neuroendocrinol, Program Reprod & Adult Endocrinol, NIH, Bldg 10-CRC,1E-3140,10 Ctr Dr, Bethesda, MD 20892 USA.
EM karel@mail.nih.gov
RI Jochmanova, Ivana/I-9011-2016
OI Jochmanova, Ivana/0000-0003-2346-461X
NR 244
TC 36
Z9 39
U1 1
U2 17
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 JNCI-J NATL CANCER I
JI JNCI-. Natl. Cancer Inst.
PD SEP
PY 2013
VL 105
IS 17
BP 1270
EP 1283
DI 10.1093/jnci/djt201
PG 14
WC Oncology
SC Oncology
GA 213EW
UT WOS:000324038500007
PM 23940289
ER
PT J
AU Arem, H
Reedy, J
Sampson, J
Jiao, L
Hollenbeck, AR
Risch, H
Mayne, ST
Stolzenberg-Solomon, RZ
AF Arem, Hannah
Reedy, Jill
Sampson, Josh
Jiao, Li
Hollenbeck, Albert R.
Risch, Harvey
Mayne, Susan T.
Stolzenberg-Solomon, Rachael Z.
TI The Healthy Eating Index 2005 and Risk for Pancreatic Cancer in the
NIH-AARP Study
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID RETIRED-PERSONS DIET; GLYCEMIC LOAD; POSTMENOPAUSAL WOMEN;
AMERICAN-ASSOCIATION; NATIONAL-INSTITUTES; LARGE COHORT; PATTERNS;
EPIDEMIOLOGY
AB Background Dietary pattern analyses characterizing combinations of food intakes offer conceptual and statistical advantages over food-and nutrient-based analyses of disease risk. However, few studies have examined dietary patterns and pancreatic cancer risk and none focused on the 2005 Dietary Guidelines for Americans. We used the Healthy Eating Index 2005 (HEI-2005) to estimate the association between meeting those dietary guidelines and pancreatic cancer risk.
Methods We calculated the HEI-2005 score for 537 218 men and women in the National Institutes of Health-American Association of Retired Persons Diet and Health Study using responses to food frequency questionnaires returned in 1995 and 1996. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of pancreatic cancer according to HEI-2005 quintiles and explored effect modification by known risk factors. P-interaction values were calculated using the Wald test. All statistical tests were two-sided.
Results We identified 2383 incident, exocrine pancreatic cancer cases (median = 10.5 years follow-up). Comparing participants who met the most dietary guidelines (Q5) with those who met the fewest guidelines (Q1), we observed a reduced risk of pancreatic cancer (HR = 0.85, 95% CI = 0.74 to 0.97). Among men there was an interaction by body mass index (P-interaction = .03), with a hazard ratio of 0.72 (95% CI = 0.59 to 0.88) comparing Q5 vs Q1 in overweight/obese men (body mass index = 25 kg/m(2)) but no association among normal weight men.
Conclusions Our findings support the hypothesis that consuming a high-quality diet, as scored by the HEI-2005, may reduce the risk of pancreatic cancer.
C1 [Arem, Hannah; Risch, Harvey; Mayne, Susan T.] Yale Univ, Sch Publ Hlth, New Haven, CT USA.
[Arem, Hannah; Reedy, Jill; Stolzenberg-Solomon, Rachael Z.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Reedy, Jill] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Jiao, Li] Baylor Coll Med, Houston, TX 77030 USA.
[Hollenbeck, Albert R.] AARP, Washington, DC USA.
[Risch, Harvey; Mayne, Susan T.] Yale Canc Ctr, New Haven, CT USA.
RP Arem, H (reprint author), 9609 Med Ctr Dr,Rm 6E324, Bethesda, MD 20892 USA.
EM Aremhe2@mail.nih.gov
FU Yale-NCI predoctoral training grant [T32 CA105666]; Intramural Research
Program of the National Institutes of Health, National Cancer Institute
FX This work was supported in part by the Yale-NCI predoctoral training
grant T32 CA105666 to STM. This research was also supported in part by
the Intramural Research Program of the National Institutes of Health,
National Cancer Institute.
NR 30
TC 21
Z9 21
U1 2
U2 8
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 JNCI-J NATL CANCER I
JI JNCI-. Natl. Cancer Inst.
PD SEP
PY 2013
VL 105
IS 17
BP 1298
EP 1305
DI 10.1093/jnci/djt185
PG 8
WC Oncology
SC Oncology
GA 213EW
UT WOS:000324038500010
PM 23949329
ER
PT J
AU Kotani, K
Sekine, Y
Ishikawa, S
Ikpot, IZ
Suzuki, K
Remaley, AT
AF Kotani, Kazuhiko
Sekine, Yoshitaka
Ishikawa, Shizukiyo
Ikpot, Imoh Z.
Suzuki, Kazuhiro
Remaley, Alan T.
TI High-Density Lipoprotein and Prostate Cancer: An Overview
SO JOURNAL OF EPIDEMIOLOGY
LA English
DT Review
DE epidemiology; HDL-cholesterol; apoA-I; prostate tumor
ID INHIBIT TUMOR-DEVELOPMENT; METABOLIC SYNDROME; HDL CHOLESTEROL;
RISK-FACTOR; CELLS; PROLIFERATION; COHORT; HYPERCHOLESTEROLEMIA;
CAPABILITY; EXPRESSION
AB Prostate cancer is a common disease in modern, developed societies and has a high incidence and mortality. High-density lipoprotein cholesterol (HDL-C) has recently received much attention as a possible risk marker of prostate cancer development and prognosis. In the present article, we summarized findings from epidemiologic studies of the association between HDL-C and prostate cancer. Low HDL-C level was found to be a risk and prognostic factor of prostate cancer in several epidemiologic studies, although the overall linkage between HDL and prostate cancer has not been definitively established. The mechanisms for this association remain uncertain; however, limited data from experimental studies imply a possible role of HDL in the pathophysiology of prostate cancer. More epidemiologic research, in combination with experimental studies, is needed in this field.
C1 [Kotani, Kazuhiko; Sekine, Yoshitaka; Ikpot, Imoh Z.; Remaley, Alan T.] NHLBI, Cardiopulm Branch, NIH, Bethesda, MD 20892 USA.
[Kotani, Kazuhiko] Jichi Med Univ, Dept Clin Lab Med, Shimotsuke, Tochigi 3290498, Japan.
[Sekine, Yoshitaka; Suzuki, Kazuhiro] Gunma Univ, Grad Sch Med, Dept Urol, Maebashi, Gumma 371, Japan.
[Ishikawa, Shizukiyo] Jichi Med Univ, Ctr Community Med, Div Community & Family Med, Shimotsuke, Tochigi 3290498, Japan.
RP Kotani, K (reprint author), Jichi Med Univ, Dept Clin Lab Med, 3311-1 Yakushiji, Shimotsuke, Tochigi 3290498, Japan.
EM kazukotani@jichi.ac.jp
FU NIH funds from NHLBI
FX None declared. Research was in part supported from intramural NIH funds
from NHLBI.
NR 35
TC 16
Z9 17
U1 1
U2 11
PU JAPAN EPIDEMIOLOGICAL ASSOC
PI TOKYO
PA C/O UNIBO PRESS, HONGO MT BLDG 4F, 7-2-2 HONGO, BUNKYO-KU, TOKYO,
113-0033, JAPAN
SN 0917-5040
J9 J EPIDEMIOL
JI J. Epidemiol.
PD SEP
PY 2013
VL 23
IS 5
BP 313
EP 319
DI 10.2188/jea.JE20130006
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 214PO
UT WOS:000324146500001
PM 23985823
ER
PT J
AU Turcotte, S
Gros, A
Hogan, K
Tran, E
Hinrichs, CS
Wunderlich, JR
Dudley, ME
Rosenberg, SA
AF Turcotte, Simon
Gros, Alena
Hogan, Katherine
Tran, Eric
Hinrichs, Christian S.
Wunderlich, John R.
Dudley, Mark E.
Rosenberg, Steven A.
TI Phenotype and Function of T Cells Infiltrating Visceral Metastases from
Gastrointestinal Cancers and Melanoma: Implications for Adoptive Cell
Transfer Therapy
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID COLORECTAL-CANCER; AUTOLOGOUS TUMOR; PROGNOSTIC-SIGNIFICANCE; TRANSFER
IMMUNOTHERAPY; LYMPHOCYTE-CULTURES; LIVER METASTASES; RANDOMIZED TRIAL;
DENDRITIC CELLS; GASTRIC-CANCER; EXPRESSION
AB Adoptive cell transfer of tumor-infiltrating lymphocytes (TILs) can mediate cancer regression in patients with metastatic melanoma, but whether this approach can be applied to common epithelial malignancies remains unclear. In this study, we compared the phenotype and function of TILs derived from liver and lung metastases from patients with gastrointestinal (GI) cancers (n = 14) or melanoma (n = 42). Fewer CD3(+) T cells were found to infiltrate GI compared with melanoma metastases, but the proportions of CD8(+) cells, T cell differentiation stage, and expression of costimulatory molecules were similar for both tumor types. Clinical-scale expansion up to similar to 50 x 10(9) T cells on average was obtained for all patients with GI cancer and melanoma. From GI tumors, however, TIL outgrowth in high-dose IL-2 yielded 22 +/- 1.4% CD3(+)CD8(+) cells compared with 63 +/- 2.4% from melanoma (p < 0.001). IFN-gamma ELISA demonstrated MHC class I-mediated reactivity of TIL against autologous tumor in 5 of 7 GI cancer patients tested (9% of 188 distinct TIL cultures) and in 9 of 10 melanoma patients (43% of 246 distinct TIL cultures). In these assays, MHC class I-mediated up-regulation of CD137 (4-1BB) expression on CD8(+) cells suggested that 0-3% of TILs expanded from GI cancer metastases were tumor-reactive. This study implies that the main challenge to the development of TIL adoptive cell transfer for metastatic GI cancers may not be the in vitro expansion of bulk TILs, but the ability to select and enrich for tumor-reactive T cells.
C1 [Turcotte, Simon; Gros, Alena; Hogan, Katherine; Tran, Eric; Hinrichs, Christian S.; Wunderlich, John R.; Dudley, Mark E.; Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
RP Rosenberg, SA (reprint author), NCI, Surg Branch, 10 Ctr Dr MSC 1201,CRC Room 3-3940, Bethesda, MD 20892 USA.
EM sar@nih.gov
OI Gros, Alena/0000-0002-1207-1880
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 45
TC 23
Z9 23
U1 0
U2 14
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD SEP 1
PY 2013
VL 191
IS 5
BP 2217
EP 2225
DI 10.4049/jimmunol.1300538
PG 9
WC Immunology
SC Immunology
GA 204TU
UT WOS:000323393300022
PM 23904171
ER
PT J
AU Kuka, M
Munitic, I
Torchia, MLG
Ashwell, JD
AF Kuka, Mirela
Munitic, Ivana
Torchia, Maria Letizia Giardino
Ashwell, Jonathan D.
TI CD70 Is Downregulated by Interaction with CD27
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID LYMPHOCYTIC CHORIOMENINGITIS VIRUS; COSTIMULATORY LIGAND CD70; T-CELL
RESPONSES; DENDRITIC CELLS; MEMBRANE-RECEPTORS; MURINE CD70; TNF FAMILY;
IN-VIVO; EXPRESSION; MEMBER
AB Engagement of the receptor CD27 by CD70 affects the magnitude and quality of T cell responses in a variety of infection models, and exaggerated signaling via this pathway results in enhanced immune responses and autoimmunity. One means by which signaling is regulated is tight control of cell surface CD70, which is expressed on dendritic cells (DCs), T cells, and B cells only upon activation. In this article, we show that a second level of regulation also is present. First, although undetectable on the cell surface by flow cytometry, immature DCs have a small pool of CD70 that continuously recycles from the plasma membrane. In addition, surface levels of CD70 on DCs and T cells were higher in mice deficient in CD27, or on DCs for which the interaction between CD70 and CD27 was precluded by blocking Abs. Binding of CD70 by its receptor resulted in downregulation of CD70 transcription and protein levels, suggesting that CD70-mediated "reverse signals" regulate its own levels. Therefore, the ability of CD70 to trigger costimulation is self-regulated when it binds its complementary receptor.
C1 [Kuka, Mirela; Munitic, Ivana; Torchia, Maria Letizia Giardino; Ashwell, Jonathan D.] NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA.
RP Ashwell, JD (reprint author), NCI, Ctr Canc Res, NIH, Bldg 37,Room 3002C, Bethesda, MD 20892 USA.
EM jda@pop.nci.nih.gov
OI KUKA, MIRELA/0000-0001-9418-1559
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health
FX This work was supported by the Intramural Research Program of the Center
for Cancer Research, National Cancer Institute, National Institutes of
Health.
NR 35
TC 9
Z9 10
U1 0
U2 5
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD SEP 1
PY 2013
VL 191
IS 5
BP 2282
EP 2289
DI 10.4049/jimmunol.1300868
PG 8
WC Immunology
SC Immunology
GA 204TU
UT WOS:000323393300029
PM 23913967
ER
PT J
AU Takai, S
Schlom, J
Tucker, J
Tsang, KY
Greiner, JW
AF Takai, Shinji
Schlom, Jeffrey
Tucker, Joanne
Tsang, Kwong Y.
Greiner, John W.
TI Inhibition of TGF-beta 1 Signaling Promotes Central Memory T Cell
Differentiation
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID GROWTH-FACTOR-BETA; TGF-BETA; INFLUENZA NUCLEOPROTEIN; LYMPHOCYTES-T;
EFFECTOR; GENERATION; IMMUNITY; PHENOTYPE; MIGRATION; DEVELOP
AB This study affirmed that isolated CD8(+) T cells express mRNA and produce TGF-beta following cognate peptide recognition. Blockage of endogenous TGF-beta with either a TGF-beta-blocking Ab or a small molecule inhibitor of TGF-beta RI enhances the generation of CD62L(high)/CD44(high) central memory CD8(+) T cells accompanied with a robust recall response. Interestingly, the augmentation within the central memory T cell pool occurs in lieu of cellular proliferation or activation, but with the expected increase in the ratio of the Eomesoderm/T-bet transcriptional factors. Yet, the signal transduction pathway(s) seems to be noncanonical, independent of SMAD or mammalian target of rapamycin signaling. Enhancement of central memory generation by TGF-beta blockade is also confirmed in human PBMCs. The findings underscore the role(s) that autocrine TGF-beta plays in T cell homeostasis and, in particular, the balance of effector/memory and central/memory T cells. These results may provide a rationale to targeting TGF-beta signaling to enhance Ag-specific CD8(+) T cell memory against a lethal infection or cancer.
C1 [Takai, Shinji; Schlom, Jeffrey; Tucker, Joanne; Tsang, Kwong Y.; Greiner, John W.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Greiner, JW (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bldg 10,Room 8B09,10 Ctr Dr, Bethesda, MD 20892 USA.
EM jg117s@nih.gov
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health
FX This work was supported by the Intramural Research Program of the Center
for Cancer Research, National Cancer Institute, National Institutes of
Health.
NR 30
TC 5
Z9 7
U1 2
U2 7
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD SEP 1
PY 2013
VL 191
IS 5
BP 2299
EP 2307
DI 10.4049/jimmunol.1300472
PG 9
WC Immunology
SC Immunology
GA 204TU
UT WOS:000323393300031
PM 23904158
ER
PT J
AU Anuradha, R
George, PJ
Hanna, LE
Chandrasekaran, V
Kumaran, P
Nutman, TB
Babu, S
AF Anuradha, Rajamanickam
George, Parakkal Jovvian
Hanna, Luke E.
Chandrasekaran, Vedachalam
Kumaran, Paul
Nutman, Thomas B.
Babu, Subash
TI IL-4-, TGF-beta-, and IL-1-Dependent Expansion of Parasite
Antigen-Specific Th9 Cells Is Associated with Clinical Pathology in
Human Lymphatic Filariasis
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID REGULATORY T-CELLS; DIFFERENTIATION; DISEASE; INTERLEUKIN-9; INFECTION;
RESPONSES; PU.1
AB Th9 cells are a subset of CD4(+) T cells, shown to be important in allergy, autoimmunity, and antitumor responses; however, their role in human infectious diseases has not been explored in detail. We identified a population of IL-9 and IL-10 coexpressing cells (lacking IL-4 expression) in normal individuals. These cells respond to antigenic and mitogenic stimulation, but are distinct from IL-9(+) Th2 cells. We also demonstrate that these Th9 cells exhibit Ag-specific expansion in a chronic helminth infection (lymphatic filariasis). Comparison of Th9 responses reveals that individuals with pathology associated with filarial infection exhibit significantly expanded frequencies of filarial Ag-induced Th9 cells, but not of IL9(+)Th2 cells in comparison with filarial-infected individuals without associated disease. Moreover, the per cell production of IL-9 is significantly higher in Th9 cells compared with IL9(+)Th2 cells, indicating that the Th9 cells are the predominant CD4(+) T cell subset producing IL-9 in the context of human infection. This expansion was reflected in elevated Ag-stimulated IL-9 cytokine levels in whole blood culture supernatants. Finally, the frequencies of Th9 cells correlated positively with the severity of lymphedema (and presumed inflammation) in filarial-diseased individuals. This expansion of Th9 cells was dependent on IL-4, TGF-beta, and IL-1 in vitro. We have therefore identified an important human CD4(+) T cell subpopulation coexpressing IL-9 and IL-10, but not IL-4, the expansion of which is associated with disease in chronic lymphatic filariasis and could potentially have an important role in the pathogenesis of other inflammatory disorders.
C1 [Anuradha, Rajamanickam; George, Parakkal Jovvian; Babu, Subash] Int Ctr Excellence Res, Natl Inst Hlth, Madras 600031, Tamil Nadu, India.
[Hanna, Luke E.; Chandrasekaran, Vedachalam; Kumaran, Paul] Natl Inst Res TB, Madras 600031, Tamil Nadu, India.
[Nutman, Thomas B.; Babu, Subash] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Babu, S (reprint author), Int Ctr Excellence Res, Natl Inst Res TB, Natl Inst Hlth, Madras 600031, Tamil Nadu, India.
EM sbabu@mail.nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health.
NR 35
TC 16
Z9 16
U1 0
U2 4
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD SEP 1
PY 2013
VL 191
IS 5
BP 2466
EP 2473
DI 10.4049/jimmunol.1300911
PG 8
WC Immunology
SC Immunology
GA 204TU
UT WOS:000323393300048
PM 23913964
ER
PT J
AU Kole, A
He, JP
Rivollier, A
Silveira, DD
Kitamura, K
Maloy, KJ
Kelsall, BL
AF Kole, Abhisake
He, JianPing
Rivollier, Aymeric
Silveira, Danielle D.
Kitamura, Kazuya
Maloy, Kevin J.
Kelsall, Brian L.
TI Type I IFNs Regulate Effector and Regulatory T Cell Accumulation and
Anti-Inflammatory Cytokine Production during T Cell-Mediated Colitis
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CHRONIC INTESTINAL INFLAMMATION; DENDRITIC CELLS; INTERFERON-ALPHA/BETA;
LY6C(HI) MONOCYTES; TH17 CELLS; SCID MICE; INDUCTION; ACTIVATION;
RECEPTOR; PROMOTE
AB We explored the function of endogenous type I IFNs (IFN-1) in the colon using the T cell adoptive transfer model of colitis. Colon mononuclear phagocytes (MPs) constitutively produced IFN-1 in a Toll/IL-1R domain-containing adapter-inducing IFN-beta-dependent manner. Transfer of CD4(+)CD45RB(hi) T cells from wild-type (WT) or IFN-alpha/beta receptor subunit 1 knockout (IFNAR1(-/-)) mice into RAG(-/-) hosts resulted in similar onset and severity of colitis. In contrast, RAG(-/-) x IFNAR1(-/-) double knockout (DKO) mice developed accelerated severe colitis compared with RAG(-/-) hosts when transferred with WT CD4(+)CD45RB(hi) T cells. IFNAR signaling on host hematopoietic cells was required to delay colitis development. MPs isolated from the colon lamina propria of IFNAR1(-/-) mice produced less IL-10, IL-1R antagonist, and IL-27 compared with WT MPs. Accelerated colitis development in DKO mice was characterized by early T cell proliferation and accumulation of CD11b(+)CD103(-) dendritic cells in the mesenteric lymph nodes, both of which could be reversed by systemic administration of IL-1R antagonist (anakinra). Cotransfer of CD4(+) CD25(+) regulatory T cells (Tregs) from WT or IFNAR1(-/-) mice prevented disease caused by CD4(+)CD45RB(hi) T cells. However, WT CD4(+)CD25(+)Foxp3(GFP+) Tregs cotransferred with CD4(+)CD45RB(hi) T cells into DKO hosts failed to expand or maintain Foxp3 expression and gained effector functions in the colon. To our knowledge, these data are the first to demonstrate an essential role for IFN-1 in the production of anti-inflammatory cytokines by gut MPs and the indirect maintenance of intestinal T cell homeostasis by both limiting effector T cell expansion and promoting Treg stability.
C1 [Kole, Abhisake; He, JianPing; Rivollier, Aymeric; Silveira, Danielle D.; Kitamura, Kazuya; Kelsall, Brian L.] NIAID, Mucosal Immunobiol Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Maloy, Kevin J.] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England.
RP Kelsall, BL (reprint author), NIAID, Mucosal Immunobiol Sect, Lab Mol Immunol, NIH, Bldg 10,Room 113,10 Ctr Dr,MSC 1886, Bethesda, MD 20892 USA.
EM bkelsall@niaid.nih.gov
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 54
TC 25
Z9 25
U1 1
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 SEP 1
PY 2013
VL 191
IS 5
BP 2771
EP 2779
DI 10.4049/jimmunol.1301093
PG 9
WC Immunology
SC Immunology
GA 204TU
UT WOS:000323393300077
PM 23913971
ER
PT J
AU Tan, IL
Mowry, EM
Steele, SU
Pardo, CA
McArthur, JC
Nath, A
Venkatesan, A
AF Tan, Ik Lin
Mowry, Ellen M.
Steele, Sonya U.
Pardo, Carlos A.
McArthur, Justin C.
Nath, Avindra
Venkatesan, Arun
TI Brainstem encephalitis: etiologies, treatment, and predictors of outcome
SO JOURNAL OF NEUROLOGY
LA English
DT Article
DE Rhombencephalitis; Brainstem encephalitis; Brain biopsy; Autoimmune;
Inflammatory; Glucose
ID HERPES-SIMPLEX ENCEPHALITIS; ACUTE DISSEMINATED ENCEPHALOMYELITIS;
INFECTIOUS ENCEPHALITIS; CLINICAL ANALYSIS; DEFINITIONS; DIAGNOSIS;
FRANCE
AB Brainstem encephalitis (BE) is an uncommon condition. We sought to characterize clinical presentations, etiologies, response to treatment, and predictors of outcome. We performed a retrospective review of non-HIV infected patients diagnosed with BE at Johns Hopkins Hospital (January 1997-April 2010). We characterized clinical and paraclinical features, and used regression models to assess associations with poor outcome. BE was diagnosed in 81 patients. An etiology was identified in 58 of 81 (71.6 %) of cases, most of which were confirmed or probable inflammatory/autoimmune conditions. Of the remaining 23 cases in which a specific diagnosis remained undefined, clinical presentation, CSF, neuroimaging studies, and outcomes were similar to the inflammatory/autoimmune group. Brain biopsy identified a specific diagnosis in 7 of 14 patients (50 %). Fifteen patients (18.5 %) either died or had a poor outcome. In multivariate logistic regression models, a higher CSF protein (per 5 mg/dl, OR = 1.11, 95 % CI: 1.03-1.20), a higher CSF glucose (per 5 mg/dl, OR = 1.36, 95 % CI: 1.09-1.70), and higher serum glucose (per 5 mg/dl, OR = 1.27, 95 % CI: 1.06-1.52) were independently associated with increased odds of poor outcome. Inflammatory and non-infectious conditions accounted for most cases of BE. Higher CSF protein and glucose were independently associated with poor outcome. In immunocompetent patients with BE of undefined etiology despite extensive investigation, a trial of immunosuppressive treatment may be warranted, though deterioration clinically or on magnetic resonance imaging should prompt a brain biopsy.
C1 [Tan, Ik Lin; Pardo, Carlos A.; McArthur, Justin C.; Venkatesan, Arun] Johns Hopkins Univ, Sch Med, Johns Hopkins Encephalitis Ctr, Baltimore, MD USA.
[Tan, Ik Lin; Mowry, Ellen M.; Steele, Sonya U.; Pardo, Carlos A.; McArthur, Justin C.; Venkatesan, Arun] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Nath, Avindra] NINDS, Sect Infect Nervous Syst, NIH, Bethesda, MD 20892 USA.
[Venkatesan, Arun] Johns Hopkins Neuroimmunol & Neuroinfectious Dis, Baltimore, MD 21287 USA.
RP Venkatesan, A (reprint author), Johns Hopkins Neuroimmunol & Neuroinfectious Dis, 600 N Wolfe St,Meyer 6-113, Baltimore, MD 21287 USA.
EM avenkat2@jhmi.edu
FU NIH [K23NS067055]; National MS Society [RG4407A2]; NIH; Biogen-Idec;
Gliamed; HHMI; Maryland Stem Cell Research Foundation; National Multiple
Sclerosis Society
FX Financial disclosure: Ellen M. Mowry: Funding NIH K23NS067055; National
MS Society RG4407A2. Receipt of free study medication from Teva
Neurological. Justin C. McArthur: Grants from NIH, Biogen-Idec, payment
from lectures, speakers' bureau in various universities, book royalties,
stock option from Gliamed. Avindra Nath: Consultant to Biogen Idec and
Diogenix. Arun Venkatesan: Grants from NIH, HHMI, Maryland Stem Cell
Research Foundation, National Multiple Sclerosis Society. Ik Lin Tan,
Sonya Steele, Carlos Pardo-Villamizar report no financial disclosure.
NR 26
TC 4
Z9 5
U1 0
U2 1
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0340-5354
J9 J NEUROL
JI J. Neurol.
PD SEP
PY 2013
VL 260
IS 9
BP 2312
EP 2319
DI 10.1007/s00415-013-6986-z
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 213ZL
UT WOS:000324099200014
PM 23749332
ER
PT J
AU Bettencourt, C
Morris, HR
Singleton, AB
Hardy, J
Houlden, H
AF Bettencourt, Conceicao
Morris, Huw R.
Singleton, Andrew B.
Hardy, John
Houlden, Henry
TI Exome sequencing expands the mutational spectrum of SPG8 in a family
with spasticity responsive to L-DOPA treatment
SO JOURNAL OF NEUROLOGY
LA English
DT Letter
ID AUTOSOMAL-DOMINANT; PARAPLEGIA; LOCUS; GENE
C1 [Bettencourt, Conceicao; Morris, Huw R.; Hardy, John; Houlden, Henry] UCL Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England.
[Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
RP Bettencourt, C (reprint author), UCL Inst Neurol, Dept Mol Neurosci, Queen Sq, London WC1N 3BG, England.
EM c.bettencourt@ucl.ac.uk
RI Hardy, John/C-2451-2009; Morris, Huw/B-8527-2008; Singleton,
Andrew/C-3010-2009; Houlden, Henry/C-1532-2008
OI Bettencourt, Conceicao/0000-0001-9090-7690; Morris,
Huw/0000-0002-5473-3774; Houlden, Henry/0000-0002-2866-7777
FU Medical Research Council [MR/J004758/1, , G0700943, G0802760, G1001253,
G108/638, G1100643, MC_G1000735]; Parkinson's UK [G-1107]; Wellcome
Trust [, 089698]
NR 8
TC 6
Z9 7
U1 0
U2 4
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0340-5354
EI 1432-1459
J9 J NEUROL
JI J. Neurol.
PD SEP
PY 2013
VL 260
IS 9
BP 2414
EP 2416
DI 10.1007/s00415-013-7044-6
PG 3
WC Clinical Neurology
SC Neurosciences & Neurology
GA 213ZL
UT WOS:000324099200031
PM 23881105
ER
PT J
AU Al-Uzri, A
Matheson, M
Gipson, DS
Mendley, SR
Hooper, SR
Yadin, O
Rozansky, DJ
Moxey-Mims, M
Furth, SL
Warady, BA
Gerson, AC
AF Al-Uzri, Amira
Matheson, Matthew
Gipson, Debbie S.
Mendley, Susan R.
Hooper, Stephen R.
Yadin, Ora
Rozansky, David J.
Moxey-Mims, Marva
Furth, Susan L.
Warady, Bradley A.
Gerson, Arlene C.
CA Chronic Kidney Dis Children CKiD
TI The Impact of Short Stature on Health-Related Quality of Life in
Children with Chronic Kidney Disease
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID GROWTH-HORMONE TREATMENT; SEX-DIFFERENCES; HEIGHT; ADOLESCENCE; COHORT;
NAPRTCS; UREMIA
AB Objectives To compare the health-related quality of life (HRQoL) of children with chronic kidney disease (CKD) and short stature (SS) with that of children with CKD and normal height (NH), to evaluate the impact of catch-up growth and growth hormone (GH) use on HRQoL, and to describe the concordance of perceptions of HRQoL between children with SS and NH and their parents.
Study design Four hundred eighty-three children and/or parents enrolled in the multicenter Chronic Kidney Disease in Children study who had completed the Pediatric Quality of Life Inventory (Version 4.0) on at least 2 Chronic Kidney Disease in Children study visits composed this substudy population. Participants were dichotomized into NH or SS groups. The demographic characteristics that varied at baseline (sex, glomerular filtration rate, and parent education) were controlled for in the main analysis evaluating the impact of catch-up growth and use of GH on HRQoL.
Results Multivariate modeling (controlling for confounding variables) revealed a significant association between both catch-up growth and GH use on parent-proxy reports of child physical functioning (P < .05) and social functioning (P < .05). Older children with CKD (15-17 years old) had significantly higher ratings than their parents on the Pediatric Quality of Life Inventory Physical, Emotional, Social, and School Functioning scales compared with younger children (8-14 years old).
Conclusion The finding that height gains and GH use are associated with increases in physical and social functioning by parent report provides additional support for interventions to improve height in children with CKD. The importance of evaluating both the parent and child perceptions of HRQoL is supported by our results.
C1 [Al-Uzri, Amira; Rozansky, David J.] Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR 97201 USA.
[Matheson, Matthew] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Gipson, Debbie S.] Mott Childrens Hosp, Dept Pediat, Ann Arbor, MI USA.
[Mendley, Susan R.] Univ Maryland, Sch Med, Dept Pediat, Baltimore, MD 21201 USA.
[Hooper, Stephen R.] Univ N Carolina, Sch Med, Carolina Inst Dev Disabil, Chapel Hill, NC USA.
[Yadin, Ora] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA.
[Moxey-Mims, Marva] NIDDK, NIH, Bethesda, MD 20892 USA.
[Furth, Susan L.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA.
[Warady, Bradley A.] Childrens Mercy Hosp & Clin, Dept Pediat, Kansas City, MO USA.
[Gerson, Arlene C.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA.
RP Al-Uzri, A (reprint author), Oregon Hlth & Sci Univ, Dept Pediat, 3181 Sw Sam Jackson Pk Rd, Portland, OR 97201 USA.
FU National Institute of Diabetes and Digestive and Kidney Diseases; Eunice
Kennedy Shriver National Institute of Child Health and Human
Development; National Heart, Lung, and Blood Institute [UO1-DK-66143,
UO1-DK-66174, U01-DK-82194, UO1-DK-66116]
FX Funded by the National Institute of Diabetes and Digestive and Kidney
Diseases, the Eunice Kennedy Shriver National Institute of Child Health
and Human Development, and the National Heart, Lung, and Blood Institute
(UO1-DK-66143, UO1-DK-66174, U01-DK-82194, and UO1-DK-66116). The
authors are solely responsible for the data analysis, and interpretation
of data, in the writing of the report, and the decision to submit the
paper for publication. The authors declare no conflicts of interest.
NR 29
TC 17
Z9 18
U1 0
U2 10
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
J9 J PEDIATR-US
JI J. Pediatr.
PD SEP
PY 2013
VL 163
IS 3
BP 736
EP +
DI 10.1016/j.jpeds.2013.03.016
PG 7
WC Pediatrics
SC Pediatrics
GA 212LQ
UT WOS:000323985300028
PM 23628375
ER
PT J
AU Chaiworapongsa, T
Romero, R
Whitten, A
Tarca, AL
Bhatti, G
Draghici, S
Chaemsaithong, P
Miranda, J
Hassan, SS
AF Chaiworapongsa, Tinnakorn
Romero, Roberto
Whitten, Amy
Tarca, Adi L.
Bhatti, Gaurav
Draghici, Sorin
Chaemsaithong, Piya
Miranda, Jezid
Hassan, Sonia S.
TI Differences and similarities in the transcriptional profile of
peripheral whole blood in early and late-onset preeclampsia: insights
into the molecular basis of the phenotype of preeclampsiaa
SO JOURNAL OF PERINATAL MEDICINE
LA English
DT Article; Proceedings Paper
CT 58th Annual Scientific Meeting of the
Society-for-Gynecologic-Investigation
CY MAR 16-26, 2011
CL Miami Beach, FL
SP Soc Gynecol Invest
DE Affymetrix; gene expression; H19; microarray; PAX gene; PCR
transcriptomic; pregnancy; white blood cell count
ID FOR-GESTATIONAL-AGE; BECKWITH-WIEDEMANN-SYNDROME; GENE-EXPRESSION
PROFILES; EPITHELIAL MEMBRANE PROTEIN-1; LINKING PLACENTAL ISCHEMIA;
MESSENGER-RNA EXPRESSION; AFRICAN-AMERICAN WOMEN; GROWTH-FACTOR
RECEPTOR; LONG-TERM MORTALITY; MICROARRAY ANALYSIS
AB Objective: Preeclampsia (PE) can be sub-divided into early-and late-onset phenotypes. The pathogenesis of these two phenotypes has not been elucidated. To gain insight into the mechanisms of disease, the transcriptional profiles of whole blood from women with early-and late-onset PE were examined.
Methods: A cross-sectional study was conducted to include women with: i) early-onset PE (diagnosed prior to 34 weeks, n = 25); ii) late-onset PE (after 34 weeks, n = 47); and iii) uncomplicated pregnancy (n = 61). Microarray analysis of mRNA expression in peripheral whole blood was undertaken using Affymetrix microarrays. Differential gene expression was evaluated using a moderated t-test (false discovery rate < 0.1 and fold change > 1.5), adjusting for maternal white blood cell count and gestational age. Validation by real-time qRT-PCR was performed in a larger sample size [early PE (n = 31), late PE (n = 72) and controls (n = 99)] in all differentially expressed genes. Gene ontology analysis and pathway analysis were performed.
Results: i) 43 and 28 genes were differentially expressed in early-and late-onset PE compared to the control group, respectively; ii) qRT-PCR confirmed the micro-array results for early and late-onset PE in 77% (33/43) and 71% (20/28) of genes, respectively; iii) 20 genes that are involved in coagulation (SERPINI2), immune regulation (VSIG4, CD24), developmental process (H19) and inflammation (S100A10) were differentially expressed in early-onset PE alone. In contrast, only seven genes that encoded proteins involved in innate immunity (LTF, ELANE) and cell-to-cell recognition in the nervous system (CNTNAP3) were differentially expressed in late-onset PE alone. Thirteen genes that encode proteins involved in host defense (DEFA4, BPI, CTSG, LCN2), tight junctions in blood-brain barrier (EMP1) and liver regeneration (ECT2) were differentially expressed in both early-and late-onset PE.
Conclusion: Early-and late-onset PE are characterized by a common signature in the transcriptional profile of whole blood. A small set of genes were differentially regulated in early-and late-onset PE. Future studies of the biological function, expression timetable and protein expression of these genes may provide insight into the pathophysiology of PE.
C1 [Chaiworapongsa, Tinnakorn; Romero, Roberto] Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, Detroit, MI 48201 USA.
[Chaiworapongsa, Tinnakorn; Romero, Roberto; Whitten, Amy; Tarca, Adi L.; Chaemsaithong, Piya; Miranda, Jezid; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Chaiworapongsa, Tinnakorn; Romero, Roberto; Whitten, Amy; Tarca, Adi L.; Chaemsaithong, Piya; Miranda, Jezid; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Chaiworapongsa, Tinnakorn; Whitten, Amy; Chaemsaithong, Piya; Miranda, Jezid; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
[Tarca, Adi L.; Bhatti, Gaurav; Draghici, Sorin] Wayne State Univ, Dept Comp Sci, Detroit, MI 48202 USA.
RP Chaiworapongsa, T (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM tchaiwor@med.wayne.edu; romeror@mail.nih.gov
FU Intramural NIH HHS [ZIA HD002400-22]; NICHD NIH HHS [HHSN275201300006C]
NR 203
TC 10
Z9 11
U1 0
U2 10
PU WALTER DE GRUYTER GMBH
PI BERLIN
PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY
SN 0300-5577
J9 J PERINAT MED
JI J. Perinat. Med.
PD SEP
PY 2013
VL 41
IS 5
BP 485
EP 504
DI 10.1515/jpm-2013-0082
PG 20
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 213JM
UT WOS:000324052900002
PM 23793063
ER
PT J
AU Lam-Rachlin, J
Romero, R
Korzeniewski, SJ
Schwartz, AG
Chaemsaithong, P
Hernandez-Andrade, E
Dong, Z
Yeo, L
Hassan, SS
Chaiworapongsa, T
AF Lam-Rachlin, Jennifer
Romero, Roberto
Korzeniewski, Steven J.
Schwartz, Alyse G.
Chaemsaithong, Piya
Hernandez-Andrade, Edgar
Dong, Zhong
Yeo, Lami
Hassan, Sonia S.
Chaiworapongsa, Tinnakorn
TI Infection and smoking are associated with decreased plasma concentration
of the anti-aging protein, alpha-klotho
SO JOURNAL OF PERINATAL MEDICINE
LA English
DT Article; Proceedings Paper
CT 33rd Annual Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine
(SMFM)
CY FEB 11-16, 2013
CL San Francisco, CA
SP Soc Maternal Fetal Med
DE Inflammation; intrauterine infection; prematurity; preterm labor;
preterm prelabor rupture of membranes
ID PRETERM PREMATURE RUPTURE; AMNIOTIC-FLUID INTERLEUKIN-6; MATERNAL SERUM
INTERLEUKIN-6; FETAL MEMBRANE DISTENSION; SONOGRAPHIC SHORT CERVIX;
NECROSIS-FACTOR-ALPHA; PLACEBO-CONTROLLED TRIAL;
PROGESTERONE-RECEPTOR-A; PITUITARY-ADRENAL AXIS; WHITE-MATTER LESIONS
AB Objective: The objective of this study was to determine whether maternal plasma concentrations of soluble alpha-klotho are different between women with microbial invasion of the intra-amniotic cavity (MIAC) and those without MIAC among preterm labor and intact membranes (PTL) or preterm prelabor rupture of membranes (pPROM).
Methods : A cross-sectional study was conducted to include women in the following groups: i) PTL with MIAC (n = 14); ii) PTL without MIAC (n = 79); iii) pPROM with MIAC (n = 30); and iv) pPROM without MIAC (n = 33). MIAC was defined as a positive amniotic fluid culture for microorganisms (aerobic/anaerobic bacteria or genital mycoplasmas). Amniotic fluid samples were obtained within 48 h of maternal blood collection. Plasma concentration of soluble alpha-klotho was determined by ELISA.
Results : i) The median plasma concentration (pg/mL) of soluble alpha-klotho was significantly lower in patients with MIAC than in those without MIAC (787.0 vs. 1117.8; P < 0.001). ii) Among patients with PTL, those with MIAC had a lower median plasma concentration (pg/mL) of soluble alpha-klotho than those without MIAC (787.0 vs. 1138.9; P = 0.007). iii) Among patients with pPROM, those with MIAC had a lower median plasma concentration (pg/mL) of soluble alpha-klotho than those without MIAC (766.4 vs. 1001.6; P = 0.045). iv) There was no significant difference in the median plasma concentration of soluble alpha-klotho between PPROM without MIAC and PTL without MIAC (1001.6 pg/mL vs. 1138.9 pg/mL, respectively; P = 0.5). v) After adjustment for potential confounders (maternal age, tobacco use, gestational age at venipuncture), soluble alpha-klotho remained significantly associated with MIAC (P = 0.02); and vi) Among patients without MIAC, smoking was significantly associated with a lower median plasma concentration soluble alpha-klotho than in non-smokers (794.2 pg/mL vs. 1382.0 pg/mL, respectively; P < 0.001); however, this difference was not observed in patients with MIAC.
Conclusions : Intra-amniotic infection occurring at preterm gestations (regardless of membrane status) was associated with a decrease in maternal plasma concentrations of soluble a-klotho. Moreover, among patients without infection, the plasma concentration of a-klotho was lower in smokers.
C1 [Lam-Rachlin, Jennifer; Romero, Roberto] Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, Detroit, MI 48201 USA.
[Lam-Rachlin, Jennifer; Romero, Roberto; Korzeniewski, Steven J.; Schwartz, Alyse G.; Chaemsaithong, Piya; Hernandez-Andrade, Edgar; Dong, Zhong; Yeo, Lami; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Lam-Rachlin, Jennifer; Korzeniewski, Steven J.; Schwartz, Alyse G.; Chaemsaithong, Piya; Hernandez-Andrade, Edgar; Yeo, Lami; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
RP Lam-Rachlin, J (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM jla@med.wayne.edu; romeror@mail.nih.gov
FU Intramural NIH HHS [ZIA HD002400-21]; NICHD NIH HHS [HHSN275201300006C]
NR 214
TC 7
Z9 7
U1 1
U2 7
PU WALTER DE GRUYTER GMBH
PI BERLIN
PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY
SN 0300-5577
J9 J PERINAT MED
JI J. Perinat. Med.
PD SEP
PY 2013
VL 41
IS 5
BP 581
EP 594
DI 10.1515/jpm-2013-0084
PG 14
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 213JM
UT WOS:000324052900015
PM 23770558
ER
PT J
AU Wu, XW
Subramaniam, S
Case, DA
Wu, KW
Brooks, BR
AF Wu, Xiongwu
Subramaniam, Sriram
Case, David A.
Wu, Katherine W.
Brooks, Bernard R.
TI Targeted conformational search with map-restrained self-guided Langevin
dynamics: Application to flexible fitting into electron microscopic
density maps
SO JOURNAL OF STRUCTURAL BIOLOGY
LA English
DT Article
DE Self-guided Langevin dynamics; Targeted conformational search; Electron
microscopy; Flexible fitting; Map-restraint
ID GROUP-II CHAPERONIN; LOW-RESOLUTION MAPS; CRYOELECTRON MICROSCOPY;
MOLECULAR-DYNAMICS; ATOMIC STRUCTURES; PROTEIN STRUCTURES; CRYO-EM;
ENERGY; MODEL; STATE
AB We present a map-restrained self-guided Langevin dynamics (MapSGLD) simulation method for efficient targeted conformational search. The targeted conformational search represents simulations under restraints defined by experimental observations and/or by user specified structural requirements. Through map-restraints, this method provides an efficient way to maintain substructures and to set structure targets during conformational searching. With an enhanced conformational searching ability of self-guided Langevin dynamics, this approach is suitable for simulating large-scale conformational changes, such as the formation of macromolecular assemblies and transitions between different conformational states. Using several examples, we illustrate the application of this method in flexible fitting of atomic structures into density maps derived from cryo-electron microscopy. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved.
C1 [Wu, Xiongwu; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA.
[Subramaniam, Sriram] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Case, David A.] Rutgers State Univ, BioMaPS Inst, Piscataway, NJ 08854 USA.
[Case, David A.] Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA.
[Wu, Katherine W.] Thomas Jefferson High Sch Sci & Technol, Alexandria, VA 22312 USA.
RP Wu, XW (reprint author), NHLBI, Lab Computat Biol, NIH, 5635 Fishers Lane,Room T919, Bethesda, MD 20892 USA.
EM wuxw@nhlbi.nih.gov
FU National Heart, Lung, and Blood Institute [Z01 HL001027-30]; National
Cancer Institute
FX This research was supported by the Intramural Research Programs of
National Heart, Lung, and Blood Institute (Z01 HL001027-30) and the
National Cancer Institute.
NR 49
TC 9
Z9 9
U1 0
U2 17
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1047-8477
J9 J STRUCT BIOL
JI J. Struct. Biol.
PD SEP
PY 2013
VL 183
IS 3
BP 429
EP 440
DI 10.1016/j.jsb.2013.07.006
PG 12
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 217GO
UT WOS:000324347900015
PM 23876978
ER
PT J
AU Ellis, RJ
Patel, D
Prodanov, T
Sadowski, S
Nilubol, N
Adams, K
Steinberg, SM
Pacak, K
Kebebew, E
AF Ellis, Ryan J.
Patel, Dhaval
Prodanov, Tamara
Sadowski, Samira
Nilubol, Naris
Adams, Karen
Steinberg, Seth M.
Pacak, Karel
Kebebew, Electron
TI Response after Surgical Resection of Metastatic Pheochromocytoma and
Paraganglioma: Can Postoperative Biochemical Remission Be Predicted?
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Article
ID MALIGNANT PHEOCHROMOCYTOMA; GENE-MUTATIONS; SURVIVAL; SDHB
AB BACKGROUND: Aggressive surgical resection with intent to cure and surgical debulking procedures are commonly recommended in patients with metastatic pheochromocytoma and paraganglioma. To date there are no data on operative outcomes of patients after surgical resection of metastatic pheochromocytoma and paraganglioma to determine if such an approach is appropriate and what factors may be associated with a favorable outcome.
STUDY DESIGN: We performed a retrospective analysis of 30 patients with metastatic pheochromocytoma/paraganglioma who underwent surgical treatment. Clinical characteristics and genetic factors were analyzed as predictors of biochemical response to surgery.
RESULTS: Thirty patients underwent a total of 42 operations, with a median follow-up time of 24 months (range 1 to 114 months). Complete disease resection (R0/R1) was achieved in 18 (42.9%) cases; 24 cases (57.1%) were debulking (R2) procedures without intent to cure. Complete biochemical remission was achieved in 10 (23.8%) cases and partial biochemical response was achieved in 23 (54.8%) cases. Patients with disease confined to the abdomen were more likely to achieve and maintain a biochemical response postoperatively than those with extra-abdominal disease (p = 0.0003). Debulking operations were significantly less likely to achieve or maintain biochemical palliation, with only 1 patient maintaining a biochemical response 12 months postoperatively (p < 0.0001). Patients were less likely to obtain pharmacologic independence after debulking (p = 0.0003), with only 2 (8.3%) not requiring pharmacotherapy 6 months after the intervention. Factors not associated with biochemical response to surgery include sex, family history, SDHB mutation status, systemic therapy, and preoperative biochemical profile.
CONCLUSIONS: Depending on the extent of disease, patients with metastatic pheochromocytoma/paraganglioma can benefit from aggressive operative intervention and resection with intent to cure. Debulking procedures are unlikely to achieve clinically significant biochemical response, with any biochemical response achieved being very short-lived. ((c) 2013 by the American College of Surgeons)
C1 [Ellis, Ryan J.; Patel, Dhaval; Sadowski, Samira; Nilubol, Naris; Kebebew, Electron] NCI, Endocrine Oncol Branch, Bethesda, MD 20892 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Off Clin Director, Bethesda, MD 20892 USA.
[Prodanov, Tamara; Adams, Karen; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Ellis, Ryan J.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
RP Kebebew, E (reprint author), NCI, Endocrine Oncol Branch, Clin Res Ctr, Bldg 10 CRC,Room 3-5581, Bethesda, MD 20892 USA.
EM kebebewe@mail.nih.gov
OI Patel, Dhaval/0000-0002-5744-568X
FU Intramural NIH HHS [Z99 CA999999]
NR 31
TC 5
Z9 5
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD SEP
PY 2013
VL 217
IS 3
BP 489
EP 496
DI 10.1016/j.jamcollsurg.2013.04.027
PG 8
WC Surgery
SC Surgery
GA 213GK
UT WOS:000324043300013
PM 23891076
ER
PT J
AU Roschewski, M
Farooqui, M
Aue, G
Wilhelm, F
Wiestner, A
AF Roschewski, M.
Farooqui, M.
Aue, G.
Wilhelm, F.
Wiestner, A.
TI Phase I study of ON 01910.Na (Rigosertib), a multikinase PI3K inhibitor
in relapsed/refractory B-cell malignancies
SO LEUKEMIA
LA English
DT Letter
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; SMALL-MOLECULE INHIBITOR; SOLID TUMORS;
CYCLIN D1; DIAGNOSIS; LYMPHOMA; CRITERIA; CANCER; AGENTS
C1 [Roschewski, M.] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA.
[Roschewski, M.; Farooqui, M.; Aue, G.; Wiestner, A.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Wilhelm, F.] Onconova Therapeut Inc, Newtown, PA USA.
RP Roschewski, M (reprint author), NCI, Metab Branch, NIH, Bethesda, MD 20892 USA.
EM wiestnea@nhlbi.nih.gov
FU Intramural NIH HHS [ZIA HL002346-09]
NR 14
TC 7
Z9 7
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD SEP
PY 2013
VL 27
IS 9
BP 1920
EP 1923
DI 10.1038/leu.2013.79
PG 5
WC Oncology; Hematology
SC Oncology; Hematology
GA 214UT
UT WOS:000324162700018
PM 23486532
ER
PT J
AU Chen, YT
Lan, Q
Zheng, TZ
Zhao, N
Holford, TR
Lerro, C
Dai, M
Huang, H
Liang, JX
Ma, SG
Leaderer, B
Boyle, P
Chanock, S
Rothman, N
Zhang, YW
AF Chen, Yingtai
Lan, Qing
Zheng, Tongzhang
Zhao, Nan
Holford, Theodore R.
Lerro, Catherine
Dai, Min
Huang, Huang
Liang, Jiaxin
Ma, Shuangge
Leaderer, Brian
Boyle, Peter
Chanock, Stephen
Rothman, Nathaniel
Zhang, Yawei
TI Polymorphisms in JAK/STAT signaling pathway genes and risk of
non-Hodgkin lymphoma
SO LEUKEMIA RESEARCH
LA English
DT Article
DE JAK/STAT signaling pathway; Non-Hodgkin lymphoma; Polymorphism;
Case-control study
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; GENOME-WIDE ASSOCIATION; JAK-STAT PATHWAY;
MOLECULAR TARGETS; IFN-GAMMA; SUSCEPTIBILITY; CELLS; CANCER;
INFLAMMATION; ACTIVATION
AB Impaired function of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway genes leads to immunodeficiency and various hematopoietic disorders. We evaluated the association between genetic polymorphisms (SNPs) in 12 JAK/STAT pathway genes (JAK3, STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, STAT6, SCOS1, SCOS2, SCOS3, and SCOS4) and NHL risk in a population-based case-control study of Connecticut women. We identified three SNPs in STAT3 (rs12949918 and rs6503695) and STAT4 (rs932169) associated with NHL risk after adjustment for multiple comparison. Our results suggest that genetic variation in JAK/STAT pathway genes may play a role in lymphomagenesis and warrants further investigation. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Chen, Yingtai; Dai, Min] Chinese Acad Med Sci, Canc Inst Hosp, Beijing 100730, Peoples R China.
[Lan, Qing; Chanock, Stephen; Rothman, Nathaniel] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
[Zheng, Tongzhang; Zhao, Nan; Holford, Theodore R.; Lerro, Catherine; Huang, Huang; Liang, Jiaxin; Ma, Shuangge; Leaderer, Brian; Zhang, Yawei] Yale Univ, Sch Publ Hlth, New Haven, CT 06520 USA.
[Boyle, Peter] Int Prevent Res Inst, Lyon, France.
RP Zhang, YW (reprint author), Yale Univ, Sch Publ Hlth, Dept Environm Hlth Sci, 60 Coll St,LEPH 440, New Haven, CT 06520 USA.
EM yawei.zhang@yale.edu
RI Boyle, Peter/A-4380-2014
OI Boyle, Peter/0000-0001-6251-0610
FU NIH [CA62006, CA165923, 1D43TW008323, 1D43TW007864, HD70324]; Intramural
Research Program of the National Cancer Institute
FX This research was supported by the NIH grants CA62006, CA165923,
1D43TW008323, 1D43TW007864, and HD70324, and the Intramural Research
Program of the National Cancer Institute.
NR 42
TC 6
Z9 7
U1 0
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0145-2126
J9 LEUKEMIA RES
JI Leuk. Res.
PD SEP
PY 2013
VL 37
IS 9
BP 1120
EP 1124
DI 10.1016/j.leukres.2013.05.003
PG 5
WC Oncology; Hematology
SC Oncology; Hematology
GA 213YW
UT WOS:000324097600023
PM 23768868
ER
PT J
AU Hosgood, HD
Chapman, RS
He, XZ
Hu, W
Tian, LW
Liu, LZ
Lai, H
Chen, W
Rothman, N
Lan, Q
AF Hosgood, H. Dean, III
Chapman, Robert S.
He, Xingzhou
Hu, Wei
Tian, Linwei
Liu, Larry Z.
Lai, Hong
Chen, Wei
Rothman, Nathaniel
Lan, Qing
TI History of lung disease and risk of lung cancer in a population with
high household fuel combustion exposures in rural China
SO LUNG CANCER
LA English
DT Article
DE Chronic lung disease; Lung cancer; Never smoking; Xuanwei; China
ID INDOOR AIR-POLLUTION; EPIDEMIOLOGIC EVIDENCE; XUAN-WEI; SMOKING;
TUBERCULOSIS; IMPROVEMENT
AB History of chronic lung diseases and household coal use for heating and cooking are established risk factors of lung cancer; however, few studies have been able to explore these risk factors simultaneously. Xuanwei, China, has some of the highest rates of lung cancer in China and most residents experience substantial in-home coal smoke exposures. Using a population-based case-control study of 498 lung cancer cases and 498 age-matched controls, we evaluated the risk of lung cancer in relation to coal smoke exposure and history of chronic lung diseases, including chronic obstructive pulmonary disease (COPD), asthma, tuberculosis (TB), chronic bronchitis, and emphysema. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by conditional logistic regression adjusting for potential confounders. We observed an increased risk of lung cancer with history of any chronic lung disease among males (OR = 14.2; 95%CI = 4.3-46.9), females (OR = 2.6; 95%CI = 1.1-63), smokers (OR = 12.7; 95%CI = 3.5-45.8), and nonsmokers (OR = 2.6; 95%CI = 1.1-6.4). Specifically, TB (OR = 83.7; 95%CI = 11.0-634.7), COPD (OR = 3.2; 95%CI = 1.7-6.0), and emphysema and chronic bronchitis (OR = 3.3; 95%CI = 1.7-6.4) were associated with increased risks. These findings suggest that history of chronic lung diseases may also increase risk of lung cancer in populations with indoor coal smoke exposures. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
C1 [Hosgood, H. Dean, III; Hu, Wei; Rothman, Nathaniel; Lan, Qing] NCI, NIH, DHHS, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Hosgood, H. Dean, III] Albert Einstein Coll Med, Div Epidemiol, Bronx, NY 10467 USA.
[Chapman, Robert S.] Chulalongkorn Univ, Coll Publ Hlth Sci, Bangkok, Thailand.
[He, Xingzhou] Chinese Ctr Dis Control & Prevent, Inst Environm Hlth & Engn, Beijing, Peoples R China.
[Tian, Linwei] Chinese Univ Hong Kong, Sch Publ Hlth & Primary Care, Hong Kong, Hong Kong, Peoples R China.
[Liu, Larry Z.] Cornell Univ, Weill Med Coll, Dept Publ Hlth, New York, NY 10021 USA.
[Lai, Hong] Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USA.
[Chen, Wei] Forest Labs Inc, Harborside Financial Ctr, Jersey City, NJ USA.
RP Hosgood, HD (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Div Epidemiol, 1300 Morris Pk Ave,Belfer 1309, Bronx, NY 10461 USA.
EM dean.hosgood@einstein.yu.edu
RI Hu, Wei/M-3524-2013; Tian, Linwei/A-9736-2009
OI Tian, Linwei/0000-0002-4739-1534
FU Chinese Academy of Preventive Medicine; Yunnan Province Antiepidemic
Station; U.S. Environmental Protection Agency; Intramural Research
Program of the National Institutes of Health
FX This research was supported by the Chinese Academy of Preventive
Medicine, the Yunnan Province Antiepidemic Station, the U.S.
Environmental Protection Agency, and the Intramural Research Program of
the National Institutes of Health.
NR 23
TC 9
Z9 13
U1 2
U2 19
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0169-5002
J9 LUNG CANCER
JI Lung Cancer
PD SEP
PY 2013
VL 81
IS 3
BP 343
EP 346
DI 10.1016/j.lungcan.2013.06.019
PG 4
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 217JI
UT WOS:000324355400005
PM 23891511
ER
PT J
AU Choy, JS
O'Toole, E
Schuster, BM
Crisp, MJ
Karpova, TS
McNally, JG
Winey, M
Gardner, MK
Basrai, MA
AF Choy, John S.
O'Toole, Eileen
Schuster, Breanna M.
Crisp, Matthew J.
Karpova, Tatiana S.
McNally, James G.
Winey, Mark
Gardner, Melissa K.
Basrai, Munira A.
TI Genome-wide haploinsufficiency screen reveals a novel role for
gamma-TuSC in spindle organization and genome stability
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID YEAST SACCHAROMYCES-CEREVISIAE; KINASE-A PATHWAY; BUDDING YEAST; MITOTIC
SPINDLE; POLE BODY; MICROTUBULE ORGANIZATION; ASPERGILLUS-NIDULANS;
ELECTRON TOMOGRAPHY; ANAPHASE SPINDLE; GENE DELETION
AB How subunit dosage contributes to the assembly and function of multimeric complexes is an important question with implications in understanding biochemical, evolutionary, and disease mechanisms. Toward identifying pathways that are susceptible to decreased gene dosage, we performed a genome-wide screen for haploinsufficient (HI) genes that guard against genome instability in Saccharomyces cerevisiae. This led to the identification of all three genes (SPC97, SPC98, and TUB4) encoding the evolutionarily conserved.-tubulin small complex (gamma-TuSC), which nucleates microtubule assembly. We found that hemizygous gamma-TuSC mutants exhibit higher rates of chromosome loss and increases in anaphase spindle length and elongation velocities. Fluorescence microscopy, fluorescence recovery after photobleaching, electron tomography, and model convolution simulation of spc98/+ mutants revealed improper regulation of interpolar (iMT) and kinetochore (kMT) microtubules in anaphase. The underlying cause is likely due to reduced levels of Tub4, as overexpression of TUB4 suppressed the spindle and chromosome segregation defects in spc98/+ mutants. We propose that gamma-TuSC is crucial for balanced assembly between iMTs and kMTs for spindle organization and accurate chromosome segregation. Taken together, the results show how gene dosage studies provide critical insights into the assembly and function of multisubunit complexes that may not be revealed by using traditional studies with haploid gene deletion or conditional alleles.
C1 [Choy, John S.; Crisp, Matthew J.; Basrai, Munira A.] NCI, Genet Branch, Bethesda, MD 20892 USA.
[Karpova, Tatiana S.; McNally, James G.] NCI, Fluorescent Imaging Facil, Lab Receptor Biol & Gene Express, Ctr Canc Res, Bethesda, MD 20892 USA.
[O'Toole, Eileen; Winey, Mark] Univ Colorado, Dept Cellular & Dev Biol, Boulder, CO 80309 USA.
[Schuster, Breanna M.; Gardner, Melissa K.] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA.
RP Basrai, MA (reprint author), NCI, Genet Branch, Bethesda, MD 20892 USA.
EM klei0091@umn.edu; basraim@mail.nih.gov
FU National Institutes of General Medical Sciences [8P41GM103431];
Biomedical Sciences; National Institutes of Health [GM-100122, GM51312];
National Cancer Institute; National Institutes of Health
FX We thank Tom Giddings and Christina Clarissa for electron microscopy
specimen preparation; Janet Meehl-Fox for yeast cultures; Charlie Boone,
Duncan Clarke, Trisha Davis, and Manuel Mendoza for reagents; Jackie
Vogel for critical reading of the manuscript and sharing unpublished
results; Hannah Klein for advice on fluctuation analysis; and Basrai
laboratory members for discussions. E.O.T. is supported by Grant
8P41GM103431 from the National Institutes of General Medical Sciences to
Andreas Hoenger (Department of Molecular, Cellular and Developmental
Biology, University of Colorado-Boulder). M.K.G. and B.M.S. are
supported by a grant from the Pew Scholars Program in the Biomedical
Sciences and National Institutes of Health Grant GM-100122. M.W. is
supported by National Institutes of Health Grant GM51312. J.S.C. and
M.A.B. are supported by the Intramural Research Program of the National
Cancer Institute, National Institutes of Health.
NR 62
TC 3
Z9 3
U1 0
U2 5
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD SEP 1
PY 2013
VL 24
IS 17
BP 2753
EP 2763
DI 10.1091/mbc.E12-12-0902
PG 11
WC Cell Biology
SC Cell Biology
GA 219GH
UT WOS:000324493800015
PM 23825022
ER
PT J
AU Farley, MN
Schmidt, LS
Mester, JL
Pena-Llopis, S
Pavia-Jimenez, A
Christie, A
Vocke, CD
Ricketts, CJ
Peterson, J
Middelton, L
Kinch, L
Grishin, N
Merino, MJ
Metwalli, AR
Xing, C
Xie, XJ
Dahia, PLM
Eng, C
Linehan, WM
Brugarolas, J
AF Farley, Megan N.
Schmidt, Laura S.
Mester, Jessica L.
Pena-Llopis, Samuel
Pavia-Jimenez, Andrea
Christie, Alana
Vocke, Cathy D.
Ricketts, Christopher J.
Peterson, James
Middelton, Lindsay
Kinch, Lisa
Grishin, Nick
Merino, Maria J.
Metwalli, Adam R.
Xing, Chao
Xie, Xian-Jin
Dahia, Patricia L. M.
Eng, Charis
Linehan, W. Marston
Brugarolas, James
TI A Novel Germline Mutation in BAP1 Predisposes to Familial Clear-Cell
Renal Cell Carcinoma
SO MOLECULAR CANCER RESEARCH
LA English
DT Article
ID UBIQUITIN HYDROLASE; SOMATIC MUTATIONS; UVEAL MELANOMA; KIDNEY CANCER;
PARAGANGLIOMA; MESOTHELIOMA
AB Renal cell carcinoma (RCC) clusters in some families. Familial RCC arises from mutations in several genes, including the von Hippel-Lindau (VHL) tumor suppressor, which is also mutated in sporadic RCC. However, a significant percentage of familial RCC remains unexplained. Recently, we discovered that the BRCA1-associated protein-1 (BAP1) gene is mutated in sporadic RCC. The BAP1 gene encodes a nuclear deubiquitinase and appears to be a classic two-hit tumor suppressor gene. Somatic BAP1 mutations are associated with high-grade, clear-cell RCC (ccRCC) and poor patient outcomes. To determine whether BAP1 predisposes to familial RCC, the BAP1 gene was sequenced in 83 unrelated probands with unexplained familial RCC. Interestingly, a novel variant (c.41T>A; p.L14H) was uncovered that cosegregated with the RCC phenotype. The p.L14H variant targets a highly conserved residue in the catalytic domain, which is frequently targeted by missense mutations. The family with the novel BAP1 variant was characterized by early-onset ccRCC, occasionally of high Fuhrman grade, and lacked other features that typify VHL syndrome. These findings suggest that BAP1 is an early-onset familial RCC predisposing gene. (C) 2013 AACR.
C1 [Farley, Megan N.; Pena-Llopis, Samuel; Pavia-Jimenez, Andrea; Christie, Alana; Xie, Xian-Jin; Brugarolas, James] Univ Texas SW Med Ctr Dallas, Simmons Comprehens Canc Ctr, Dallas, TX 75390 USA.
[Farley, Megan N.] Univ Texas SW Med Ctr Dallas, Dept Clin Genet, Dallas, TX 75390 USA.
[Pena-Llopis, Samuel; Pavia-Jimenez, Andrea; Brugarolas, James] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
[Pena-Llopis, Samuel; Pavia-Jimenez, Andrea; Brugarolas, James] Univ Texas SW Med Ctr Dallas, Dept Dev Biol, Dallas, TX 75390 USA.
[Kinch, Lisa; Grishin, Nick] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
[Xing, Chao] Univ Texas SW Med Ctr Dallas, McDermott Ctr Human Growth & Dev, Dallas, TX 75390 USA.
[Dahia, Patricia L. M.] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, Dept Med, San Antonio, TX 78229 USA.
[Schmidt, Laura S.; Vocke, Cathy D.; Ricketts, Christopher J.; Peterson, James; Middelton, Lindsay; Metwalli, Adam R.; Linehan, W. Marston] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Merino, Maria J.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Schmidt, Laura S.] SAIC Frederick Inc, Basic Sci Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Mester, Jessica L.; Eng, Charis] Cleveland Clin, Genom Med Inst, Cleveland, OH USA.
[Mester, Jessica L.; Eng, Charis] Cleveland Clin, Lerner Res Inst, Cleveland, OH USA.
[Mester, Jessica L.; Eng, Charis] Cleveland Clin, Taussig Canc Inst, Cleveland, OH USA.
[Eng, Charis] Case Western Reserve Univ, Sch Med, Dept Genet & Genome Sci, Cleveland, OH USA.
[Eng, Charis] Case Western Reserve Univ, Sch Med, CASE Comprehens Canc Ctr, Cleveland, OH USA.
RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, Bldg 10 CRC 1W5940, Bethesda, MD 20892 USA.
EM WML@nih.gov; james.brugarolas@utsouthwestern.edu
OI Eng, Charis/0000-0002-3693-5145
FU Intramural Research Program of the NIH, NCI, Center for Cancer Research;
Frederick National Laboratory for Cancer Research, NIH
[HHSN261200800001E]; [CPRIT RP101075]; [1P30CA142543]
FX This work was supported by private donations in honor of Mr. Thomas M.
Green, Sr. and of a second anonymous patient of Dr. J. Brugarolas as
well as grants CPRIT RP101075 and 1P30CA142543. In addition, the work
was also supported by grants from the Intramural Research Program of the
NIH, NCI, Center for Cancer Research, and was funded, in part, with
federal funds from the Frederick National Laboratory for Cancer
Research, NIH, under Contract HHSN261200800001E (to L. Schmidt).
NR 33
TC 46
Z9 46
U1 2
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1541-7786
J9 MOL CANCER RES
JI Mol. Cancer Res.
PD SEP
PY 2013
VL 11
IS 9
BP 1061
EP 1071
DI 10.1158/1541-7786.MCR-13-0111
PG 11
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 219RE
UT WOS:000324525500010
PM 23709298
ER
PT J
AU Larocca, C
Cohen, JR
Fernando, RI
Huang, B
Hamilton, DH
Palena, C
AF Larocca, Cecilia
Cohen, Joseph R.
Fernando, Romaine I.
Huang, Bruce
Hamilton, Duane H.
Palena, Claudia
TI An Autocrine Loop between TGF-beta 1 and the Transcription Factor
Brachyury Controls the Transition of Human Carcinoma Cells into a
Mesenchymal Phenotype
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID GROWTH-FACTOR-BETA; TGF-BETA; CANCER PROGRESSION; STEM-CELLS; GENE;
BREAST; DISEASE; MOUSE; SNAIL; EMT
AB The epithelial-mesenchymal transition (EMT) is a process associated with the metastasis of solid tumors as well as with the acquisition of resistance to standard anticancer modalities. A major initiator of EMT in carcinoma cells is TGF-beta, which has been shown to induce the expression of several transcription factors ultimately responsible for initiating and maintaining the EMT program. We have previously identified Brachyury, a T-box transcription factor, as an inducer of mesenchymal features in human carcinoma cells. In this study, a potential link between Brachyury and TGF-beta signaling has been investigated. The results show for the first time that Brachyury expression is enhanced during TGF-beta 1-induced EMT in various human cancer cell lines, and that a positive feedback loop is established between Brachyury and TGF-beta 1 in mesenchymal-like tumor cells. In this context, Brachyury overexpression is shown to promote upregulation of TGF-beta 1 at the mRNA and protein levels, an effect mediated by activation of the TGF-beta 1 promoter in the presence of high levels of Brachyury. Furthermore, inhibition of TGF-beta 1 signaling by a small-molecule inhibitor of TGF-beta receptor type I decreases Brachyury expression, induces a mesenchymal-to-epithelial transition, and renders cancer cells more susceptible to chemotherapy. This study thus has implications for the future development of clinical trials using TGF-beta inhibitors in combination with other anticancer agents. (C) 2013 AACR.
C1 [Larocca, Cecilia; Cohen, Joseph R.; Fernando, Romaine I.; Huang, Bruce; Hamilton, Duane H.; Palena, Claudia] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Palena, C (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B14,MSC 1750, Bethesda, MD 20892 USA.
EM palenac@mail.nih.gov
FU Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, NIH
FX This work is supported by the funds from the Intramural Research Program
of the Center for Cancer Research, National Cancer Institute, NIH.
NR 49
TC 24
Z9 27
U1 0
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD SEP
PY 2013
VL 12
IS 9
BP 1805
EP 1815
DI 10.1158/1535-7163.MCT-12-1007
PG 11
WC Oncology
SC Oncology
GA 214YE
UT WOS:000324174600011
PM 23783250
ER
PT J
AU Nelson, F
Salter, A
Narayana, P
Gustafson, T
Conwit, R
Wang, J
Cofield, SS
Cutter, G
Lublin, FD
Wolinsky, J
AF Nelson, Flavia
Salter, Amber
Narayana, Ponnada
Gustafson, Tarah
Conwit, Robin
Wang, Jing
Cofield, Stacey S.
Cutter, Gary
Lublin, Fred D.
Wolinsky, Jerry
TI MRI OUTCOMES AND MS DIAGNOSIS CRITERIA IN THE COMBIRX TRIAL
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
CT 18th Annual Meeting of
Americas-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis
(ACTRIMS)
CY MAY 31-JUN 01, 2013
CL Orlando, FL
SP Americas Comm Treatment & Res Multiple Sclerosis
DE Epidemiology of MS
C1 [Nelson, Flavia; Narayana, Ponnada; Wolinsky, Jerry] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA.
[Salter, Amber; Wang, Jing; Cofield, Stacey S.; Cutter, Gary] Univ Alabama Birmingham, Birmingham, AL USA.
[Gustafson, Tarah; Lublin, Fred D.] Mt Sinai Sch Med, Corinne Goldsmith Dickinson Ctr Multiple Sclerosi, New York, NY USA.
[Conwit, Robin] NINDS, NIH, Bethesda, MD 20892 USA.
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 1352-4585
J9 MULT SCLER J
JI Mult. Scler. J.
PD SEP
PY 2013
VL 19
IS 10
BP 1392
EP 1393
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 208VM
UT WOS:000323709300028
ER
PT J
AU Oh, J
Saidha, S
Chen, M
Smith, S
Prince, J
Jones, C
van Zijl, P
Diener-West, M
Reich, DS
Calabresi, PA
AF Oh, Jiwon
Saidha, Shiv
Chen, Min
Smith, Seth
Prince, Jerry
Jones, Craig
van Zijl, Peter
Diener-West, Marie
Reich, Daniel S.
Calabresi, Peter A.
TI RELATIVE CLINICAL UTILITY OF QUANTITATIVE MRI MEASURES IN THE SPINAL
CORD IN MS PATIENTS
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
CT 18th Annual Meeting of
Americas-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis
(ACTRIMS)
CY MAY 31-JUN 01, 2013
CL Orlando, FL
SP Americas Comm Treatment & Res Multiple Sclerosis
DE Imaging and MS
C1 [Oh, Jiwon; Saidha, Shiv; Chen, Min; Prince, Jerry; Diener-West, Marie; Calabresi, Peter A.] Johns Hopkins Univ, Baltimore, MD USA.
[Smith, Seth] Vanderbilt Univ, Inst Imaging Sci, Dept Radiol & Radiol Sci Biomed Engn Phys & Astro, Nashville, TN 37235 USA.
[Jones, Craig; van Zijl, Peter] Johns Hopkins Univ, Dept Radiol & Radiol Sci, Baltimore, MD USA.
[Jones, Craig; van Zijl, Peter] Kennedy Krieger Inst, FM Kirby Ctr Funct Brain Imaging, Baltimore, MD USA.
[Reich, Daniel S.] NINDS, Translat Neuroradiol Unit, Bethesda, MD 20892 USA.
[Reich, Daniel S.] Johns Hopkins Univ, Bethesda, MD USA.
[Reich, Daniel S.] Johns Hopkins Univ, Dept Radiol & Radiol Sci, Bethesda, MD USA.
RI Prince, Jerry/A-3281-2010; Reich, Daniel/E-5701-2010
OI Prince, Jerry/0000-0002-6553-0876; Reich, Daniel/0000-0002-2628-4334
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 1352-4585
J9 MULT SCLER J
JI Mult. Scler. J.
PD SEP
PY 2013
VL 19
IS 10
BP 1392
EP 1392
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 208VM
UT WOS:000323709300027
ER
PT J
AU Nash, RA
Hutton, GJ
Racke, MK
Popat, U
Devine, SM
Georges, GE
Griffith, LM
Muraro, PA
Openshaw, H
Sayre, P
Stuve, O
Arnold, DL
Spychala, M
Lim, N
Malhotra, S
Phippard, D
Wundes, A
Kraft, GH
Bowen, JD
AF Nash, Richard A.
Hutton, George J.
Racke, Michael K.
Popat, Uday
Devine, Steven M.
Georges, George E.
Griffith, Linda M.
Muraro, Paolo A.
Openshaw, Harry
Sayre, Peter
Stuve, Olaf
Arnold, Douglas L.
Spychala, Meagan
Lim, Noha
Malhotra, Sachin
Phippard, Deborah
Wundes, Annette
Kraft, George H.
Bowen, James D.
TI 2-YEAR FOLLOW-UP RESULTS OF THE HALT MS CLINICAL TRIAL (ITN033AI)
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
CT 18th Annual Meeting of
Americas-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis
(ACTRIMS)
CY MAY 31-JUN 01, 2013
CL Orlando, FL
SP Americas Comm Treatment & Res Multiple Sclerosis
DE Disease-modifying treatments in MS; Imaging and MS; Immunology and MS
C1 [Nash, Richard A.] PSL, Colorado Blood Canc Inst, Denver, CO USA.
[Hutton, George J.] Baylor Coll Med, Houston, TX 77030 USA.
[Racke, Michael K.; Devine, Steven M.] Ohio State Univ, Wexner Med Ctr, Columbus, OH 43210 USA.
[Popat, Uday] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Georges, George E.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Griffith, Linda M.] NIAID, NIH, Bethesda, MD 20892 USA.
[Muraro, Paolo A.] Univ London Imperial Coll Sci Technol & Med, London, England.
[Openshaw, Harry] City Hope Natl Med Ctr, Duarte, CA 91010 USA.
[Sayre, Peter; Phippard, Deborah] Immune Tolerance Network, San Francisco, CA USA.
[Stuve, Olaf] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Arnold, Douglas L.] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada.
[Arnold, Douglas L.] NeuroRx Res, Montreal, PQ, Canada.
[Spychala, Meagan] Rho Fed Syst Div Inc, Chapel Hill, NC USA.
[Lim, Noha; Malhotra, Sachin] Immune Tolerance Network, Boston, MA USA.
[Wundes, Annette; Kraft, George H.] Univ Washington, Seattle, WA 98195 USA.
[Bowen, James D.] Swedish Med Ctr, Seattle, WA USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1352-4585
J9 MULT SCLER J
JI Mult. Scler. J.
PD SEP
PY 2013
VL 19
IS 10
MA P20
BP 1407
EP 1408
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 208VM
UT WOS:000323709300055
ER
PT J
AU Oh, J
Seigo, M
Saidha, S
Sotirchos, ES
Zackowski, KM
Chen, M
Prince, J
Diener-West, M
Calabresi, PA
Reich, DS
AF Oh, Jiwon
Seigo, Michaela
Saidha, Shiv
Sotirchos, Elias S.
Zackowski, Kathleen M.
Chen, Min
Prince, Jerry
Diener-West, Marie
Calabresi, Peter A.
Reich, Daniel S.
TI SPINAL CORD NORMALIZATION IN MULTIPLE SCLEROSIS
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
CT 18th Annual Meeting of
Americas-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis
(ACTRIMS)
CY MAY 31-JUN 01, 2013
CL Orlando, FL
SP Americas Comm Treatment & Res Multiple Sclerosis
DE Imaging and MS
C1 [Oh, Jiwon; Seigo, Michaela; Saidha, Shiv; Sotirchos, Elias S.; Chen, Min; Prince, Jerry; Diener-West, Marie] Johns Hopkins Univ, Baltimore, MD USA.
[Zackowski, Kathleen M.; Calabresi, Peter A.] Johns Hopkins Sch Med, Baltimore, MD USA.
[Reich, Daniel S.] NINDS, Translat Neuroradiol Unit, Bethesda, MD 20892 USA.
RI Prince, Jerry/A-3281-2010; Reich, Daniel/E-5701-2010
OI Prince, Jerry/0000-0002-6553-0876; Reich, Daniel/0000-0002-2628-4334
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 1352-4585
J9 MULT SCLER J
JI Mult. Scler. J.
PD SEP
PY 2013
VL 19
IS 10
MA P22
BP 1408
EP 1409
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 208VM
UT WOS:000323709300057
ER
PT J
AU Bashir, K
Cofield, SS
Cutter, G
Wolinsky, J
Gustafson, T
Conwit, R
Salter, A
Wang, J
Lublin, FD
AF Bashir, Khurram
Cofield, Stacey S.
Cutter, Gary
Wolinsky, Jerry
Gustafson, Tarah
Conwit, Robin
Salter, Amber
Wang, Jing
Lublin, Fred D.
TI CLINICAL OUTCOMES AND MS DIAGNOSIS CRITERIA IN THE COMBIRX TRIAL
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
CT 18th Annual Meeting of
Americas-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis
(ACTRIMS)
CY MAY 31-JUN 01, 2013
CL Orlando, FL
SP Americas Comm Treatment & Res Multiple Sclerosis
DE Epidemiology of MS
C1 [Bashir, Khurram; Cofield, Stacey S.; Cutter, Gary; Salter, Amber; Wang, Jing] Univ Alabama Birmingham, Birmingham, AL USA.
[Wolinsky, Jerry] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA.
[Gustafson, Tarah; Lublin, Fred D.] Corinne Goldsmith Dickinson Ctr Multiple Sclerosi, New York, NY USA.
[Conwit, Robin] NINDS, NIH, Bethesda, MD 20892 USA.
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 1352-4585
J9 MULT SCLER J
JI Mult. Scler. J.
PD SEP
PY 2013
VL 19
IS 10
MA P42
BP 1418
EP 1419
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 208VM
UT WOS:000323709300077
ER
PT J
AU Jourdan, T
Godlewski, G
Cinar, R
Bertola, A
Szanda, G
Liu, J
Tam, J
Han, T
Mukhopadhyay, B
Skarulis, MC
Ju, C
Aouadi, M
Czech, MP
Kunos, G
AF Jourdan, Tony
Godlewski, Grzegorz
Cinar, Resat
Bertola, Adeline
Szanda, Gergo
Liu, Jie
Tam, Joseph
Han, Tiffany
Mukhopadhyay, Bani
Skarulis, Monica C.
Ju, Cynthia
Aouadi, Myriam
Czech, Michael P.
Kunos, George
TI Activation of the Nlrp3 inflammasome in infiltrating macrophages by
endocannabinoids mediates beta cell loss in type 2 diabetes
SO NATURE MEDICINE
LA English
DT Article
ID THIOREDOXIN-INTERACTING PROTEIN; INDUCED INSULIN-RESISTANCE; CB1
RECEPTOR ANTAGONIST; DIET-INDUCED OBESITY; CANNABINOID RECEPTORS; NALP3
INFLAMMASOME; ADIPOSE-TISSUE; BODY-WEIGHT; ER STRESS; MICE
AB Type 2 diabetes mellitus (T2DM) progresses from compensated insulin resistance to beta cell failure resulting in uncompensated hyperglycemia, a process replicated in the Zucker diabetic fatty (ZDF) rat, The Nlrp3 inflammasome has been implicated in obesity-induced insulin resistance and beta cell failure. Endocannabinoids contribute to insulin resistance through activation of peripheral CB1 receptors (CB(1)Rs) and also promote beta cell failure. Here we show that beta cell failure in adult ZDF rats is not associated with CB1R signaling in beta cells, but rather in M1 macrophages infiltrating into pancreatic islets, and that this leads to activation of the Nlrp3-ASC inflammasome in the macrophages. These effects are replicated in vitro by incubating wild-type human or rodent macrophages, but not macrophages from CB1R-deficient (Cnr1(-/-)) or Nirp3(-/-) mice, with the endocannabinoid anandamide. Peripheral CB1R blockade, in vivo depletion of macrophages or macrophage-specific knockdown of CB1R reverses or prevents these changes and restores normoglycemia and glucose-induced insulin secretion. These findings implicate endocannabinoids and inflammasome activation in beta cell failure and identify macrophage-expressed CB1R as a therapeutic target in T2DM.
C1 [Jourdan, Tony; Godlewski, Grzegorz; Cinar, Resat; Szanda, Gergo; Liu, Jie; Tam, Joseph; Han, Tiffany; Mukhopadhyay, Bani; Kunos, George] NIAAA, Lab Physiol Studies, US Natl Inst Hlth, Bethesda, MD USA.
[Bertola, Adeline] NIAAA, Lab Liver Dis, US Natl Inst Hlth, Bethesda, MD USA.
[Skarulis, Monica C.] NIDDK, Diabet Endocrinol & Obes Branch, US Natl Inst Hlth, Bethesda, MD USA.
[Ju, Cynthia] Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Aurora, CO USA.
[Aouadi, Myriam; Czech, Michael P.] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA USA.
RP Jourdan, T (reprint author), NIAAA, Lab Physiol Studies, US Natl Inst Hlth, Bethesda, MD USA.
EM jourdant@mail.nih.gov; george.kunos@nih.gov
OI CINAR, RESAT/0000-0002-8597-7253; Bertola, Adeline/0000-0002-4885-8423
FU intramural NIH funds; NIH [DK085753, AI046629]
FX We thank J.F. McElroy and R.J. Chorvat (Jenrin Discovery) for providing
the CB1R antagonist JD5037 and its inactive diastereomer, O.
Gavrilova (NIDDK, US National Institutes of Health (NIH)) for advice on
pancreatic islet isolation, J. Harvey-White for technical assistance, D.
Feng for FACS analyses, R. Kechrid for assistance with the animal
studies and P. Staker for collecting human blood specimens. This study
was supported by intramural NIH funds. The work from M.P.C.'s laboratory
was supported by grants from the NIH (DK085753 and AI046629).
NR 59
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PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD SEP
PY 2013
VL 19
IS 9
BP 1132
EP 1140
DI 10.1038/nm.3265
PG 9
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 213TP
UT WOS:000324083500027
PM 23955712
ER
PT J
AU Emblem, KE
Mouridsen, K
Bjornerud, A
Farrar, CT
Jennings, D
Borra, RJH
Wen, PY
Ivy, P
Batchelor, TT
Rosen, BR
Jain, RK
Sorensen, AG
AF Emblem, Kyrre E.
Mouridsen, Kim
Bjornerud, Atle
Farrar, Christian T.
Jennings, Dominique
Borra, Ronald J. H.
Wen, Patrick Y.
Ivy, Percy
Batchelor, Tracy T.
Rosen, Bruce R.
Jain, Rakesh K.
Sorensen, A. Gregory
TI Vessel architectural imaging identifies cancer patient responders to
anti-angiogenic therapy
SO NATURE MEDICINE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MAGNETIC-SUSCEPTIBILITY; ANTIANGIOGENIC
THERAPY; GLIOBLASTOMA PATIENTS; TUMOR ANGIOGENESIS; KINASE INHIBITOR; MR
CONTRAST; VASCULATURE; MICROCIRCULATION; MECHANISMS
AB Measurement of vessel caliber by magnetic resonance imaging (MRI) is a valuable technique for in vivo monitoring of hemodynamic status and vascular development, especially in the brain. Here, we introduce a new paradigm in MRI termed vessel architectural imaging (VAI) that exploits an overlooked temporal shift in the magnetic resonance signal, forming the basis for vessel caliber estimation, and show how this phenomenon can reveal new information on vessel type and function not assessed by any other noninvasive imaging technique. We also show how this biomarker can provide new biological insights into the treatment of patients with cancer. As an example, we demonstrate using VAI that anti-angiogenic therapy can improve microcirculation and oxygen saturation and reduce vessel calibers in patients with recurrent glioblastomas and, more crucially, that patients with these responses have prolonged survival. Thus, VAI has the potential to identify patients who would benefit from therapies.
C1 [Emblem, Kyrre E.; Mouridsen, Kim; Farrar, Christian T.; Jennings, Dominique; Borra, Ronald J. H.; Rosen, Bruce R.; Sorensen, A. Gregory] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Emblem, Kyrre E.; Mouridsen, Kim; Farrar, Christian T.; Jennings, Dominique; Borra, Ronald J. H.; Rosen, Bruce R.; Sorensen, A. Gregory] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA.
[Emblem, Kyrre E.; Mouridsen, Kim; Farrar, Christian T.; Jennings, Dominique; Borra, Ronald J. H.; Wen, Patrick Y.; Batchelor, Tracy T.; Rosen, Bruce R.; Jain, Rakesh K.; Sorensen, A. Gregory] Harvard Univ, Sch Med, Boston, MA USA.
[Emblem, Kyrre E.; Bjornerud, Atle] Oslo Univ Hosp, Intervent Ctr, Oslo, Norway.
[Mouridsen, Kim] Univ Aarhus, Ctr Funct Integrat Neurosci, Aarhus, Denmark.
[Mouridsen, Kim] Univ Aarhus, MINDLab, Aarhus, Denmark.
[Bjornerud, Atle] Univ Oslo, Dept Phys, Oslo, Norway.
[Borra, Ronald J. H.] Turku Univ Hosp, Med Imaging Ctr Southwest Finland, FIN-20520 Turku, Finland.
[Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA.
[Ivy, Percy] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Batchelor, Tracy T.; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA.
[Batchelor, Tracy T.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Sorensen, A. Gregory] Siemens Healthcare Hlth Serv, Malvern, PA USA.
RP Emblem, KE (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
EM kyrre@mmr.mgh.harvard.edu
RI Emblem, Kyrre/H-6691-2012;
OI Emblem, Kyrre/0000-0002-6580-9519; Borra, Ronald/0000-0001-8072-1243
FU US Public Health Service [R21CA117079, S10RR023401, S10RR019307,
S10RR019254, S10RR023043, S10RR021110, R01CA137254, R01CA129371,
5R01NS060918, K24CA125440, P0ICA80124, K25AG029415]; US National Cancer
Institute [NCT00035656]; SAIC-Frederick Inc. [26XS263]; Norwegian
Research Council [191088/F20]; South-Eastern Norway Regional Health
Authority Grant [2013069]; Danish Research Foundation (Center of
Functionally Integrative Neuroscience); Ministry of Science, Innovation
and Technology Denmark (Investment Capital for University Research);
Sigrid Juselius Foundation; Instrumentarium Research Foundation; Academy
of Finland; Paulo Foundation; Finnish Medical Foundation; Harvard
Catalyst Harvard Clinical and Translational Science Center (US National
Institutes of Health Award) [UL1 RR 025758, M01-RR-01066]; Harvard
University
FX The authors thank T. Stylianopoulos (Department of Mechanical and
Manufacturing Engineering, University of Cyprus) and J.W. Baish
(Department of Mechanical and Biomedical Engineering, Bucknell
University) for critical reading of this manuscript. This work was
funded by the US Public Health Service (grants R21CA117079, S10RR023401,
S10RR019307, S10RR019254, S10RR023043, S10RR021110, R01CA137254,
R01CA129371, 5R01NS060918, K24CA125440, P0ICA80124 and K25AG029415), by
the US National Cancer Institute (http://www.clinicaltrials.gov/,
NCT00035656); SAIC-Frederick Inc. grant 26XS263; Norwegian Research
Council grant 191088/F20; South-Eastern Norway Regional Health Authority
Grant 2013069; the Danish Research Foundation (Center of Functionally
Integrative Neuroscience); the Ministry of Science, Innovation and
Technology Denmark (Investment Capital for University Research); the
Sigrid Juselius Foundation; the Instrumentarium Research Foundation; the
Academy of Finland; the Paulo Foundation; and the Finnish Medical
Foundation. This work was conducted with support from Harvard Catalyst
Harvard Clinical and Translational Science Center (US National
Institutes of Health Award nos. UL1 RR 025758 and M01-RR-01066 and
financial contributions from Harvard University and its affiliated
academic healthcare centers). The content is solely the responsibility
of the authors and does not necessarily represent the official views of
Harvard Catalyst, Harvard University and its affiliated academic health
care centers, the US National Center for Research Resources or the US
National Institutes of Health.
NR 27
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U1 1
U2 29
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD SEP
PY 2013
VL 19
IS 9
BP 1178
EP 1183
DI 10.1038/nm.3289
PG 6
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 213TP
UT WOS:000324083500035
PM 23955713
ER
PT J
AU Kenworthy, L
Yerys, BE
Weinblatt, R
Abrams, DN
Wallace, GL
AF Kenworthy, Lauren
Yerys, Benjamin E.
Weinblatt, Rachel
Abrams, Danielle N.
Wallace, Gregory L.
TI Motor Demands Impact Speed of Information Processing in Autism Spectrum
Disorders
SO NEUROPSYCHOLOGY
LA English
DT Article
DE autism spectrum disorder; processing speed; motor abilities;
communication
ID HIGH-FUNCTIONING AUTISM; ASPERGER-SYNDROME; COGNITIVE-ABILITIES;
INSPECTION TIME; WISC-IV; CHILDREN; INTELLIGENCE; IMPAIRMENT; DYSPRAXIA;
ADHD
AB The apparent contradiction between preserved or even enhanced perceptual processing speed on inspection time tasks in autism spectrum disorders (ASD) and impaired performance on complex processing speed tasks that require motor output (e.g., Wechsler Processing Speed Index) has not yet been systematically investigated. This study investigates whether adding motor output demands to an inspection time task impairs ASD performance compared to that of typically developing control (TDC) children. The performance of children with ASD (n = 28; mean Full Scale IQ (FSIQ) = 115) and TDC (n = 25; mean FSIQ = 122) children was compared on processing speed tasks with increasing motor demand. Correlations were run between ASD task performance and Autism Diagnostic Observation Schedule (ADOS) Communication scores. Performance by the ASD and TDC groups on a simple perceptual processing speed task with minimal motor demand was equivalent, though it diverged (ASD worse than TDC) on 2 tasks with the same stimuli but increased motor output demands. ASD performance on the moderate but not the high speeded motor output demand task was negatively correlated with ADOS communication symptoms. These data address the apparent contradiction between preserved inspection time in the context of slowed "processing speed" in ASD. They show that processing speed is preserved when motor demands are minimized, but that increased motor output demands interfere with the ability to act on perceptual processing of simple stimuli. Reducing motor demands (e.g., through the use of computers) may increase the capacity of people with ASD to demonstrate good perceptual processing in a variety of educational, vocational, and social settings.
C1 [Kenworthy, Lauren; Yerys, Benjamin E.; Weinblatt, Rachel; Abrams, Danielle N.] Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders, Rockville, MD 20850 USA.
[Yerys, Benjamin E.] Childrens Hosp Philadelphia, Ctr Autism Res, Philadelphia, PA 19104 USA.
[Wallace, Gregory L.] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA.
RP Kenworthy, L (reprint author), Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders, 15245 Shady Grove Rd,Suite 350, Rockville, MD 20850 USA.
EM lkenwort@cnmc.org
OI Wallace, Gregory/0000-0003-0329-5054
FU NIH, National Institute of Mental Health Intramural Research Program;
NIH, National Institute of Mental Health [K23MH086111]; Singer Family
Foundation; Isadore and Bertha Gudelsky Family Foundation
FX We thank the children and families who offered their time for the
current study. We also thank Mike Anderson for use of task stimuli.
There are no conflicts of interest, financial or otherwise, for the
authors involved directly or indirectly with this article. Lauren
Kenworthy and Gregory L. Wallace were supported by the NIH, National
Institute of Mental Health Intramural Research Program. Benjamin E.
Yerys was supported by a K23 Career Development Award from the NIH,
National Institute of Mental Health (K23MH086111). Lauren Kenworthy and
Benjamin E. Yerys were also supported by awards from The Singer Family
Foundation and The Isadore and Bertha Gudelsky Family Foundation.
NR 28
TC 5
Z9 5
U1 3
U2 13
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0894-4105
J9 NEUROPSYCHOLOGY
JI Neuropsychology
PD SEP
PY 2013
VL 27
IS 5
BP 529
EP 536
DI 10.1037/a0033599
PG 8
WC Psychology, Clinical; Neurosciences; Psychology
SC Psychology; Neurosciences & Neurology
GA 212VV
UT WOS:000324011800003
PM 23937483
ER
PT J
AU Yerys, BE
Kenworthy, L
Jankowski, KF
Strang, J
Wallace, GL
AF Yerys, Benjamin E.
Kenworthy, Lauren
Jankowski, Kathryn F.
Strang, John
Wallace, Gregory L.
TI Separate Components of Emotional Go/No-Go Performance Relate to Autism
Versus Attention Symptoms in Children With Autism
SO NEUROPSYCHOLOGY
LA English
DT Article
DE autism; attention-deficit/hyperactivity disorder; cognitive control;
response inhibition; emotion
ID DEFICIT/HYPERACTIVITY DISORDER; EXECUTIVE FUNCTIONS; SPECTRUM DISORDERS;
SUSTAINED ATTENTION; ADHD; HYPERACTIVITY; ENDOPHENOTYPES; INDIVIDUALS;
IMPAIRMENT; INTERVIEW
AB Objective: The present investigation examined whether higher functioning children with autism would demonstrate impaired response inhibition performance in an emotional go/no-go task, and whether severity of attention-deficit/hyperactivity disorder (ADHD) or autism symptoms correlated with performance. Method: Forty-four children (21 meeting criteria for autism; 23 typically developing controls [TDCs]) completed an emotional go/no-go task in which an emotional facial expression (angry, fearful, happy, or sad) was the go stimulus and a neutral facial expression was the no-go stimulus, and vice versa. Results: The autism group was faster than the TDC group on all emotional go,trials. Moreover, the children in the autism group who had the fastest reaction times on emotional go trials were rated as having the greatest number of symptoms (Autism Diagnostic Observation Schedule Social + Communication score), even after accounting for the association with ADHD symptoms. The autism group also made more impulsive responses (i.e., lower d', more false alarms) than the TDC group on all trials. As d' decreased or false alarms increased, so. did ADHD symptoms. Hyperactivity/impulsivity symptoms were significantly correlated with false alarms, but inattention symptoms were not. There was not a significant relationship between no-go false alarms and autism symptoms; even after partialing out associations with autism symptoms, the significant correlation between ADHD symptoms and no-go false alarms remained. Conclusion: The present findings support a comorbidity model that argues for shared and independent risk factors, because ADHD and autism symptoms related to independent aspects of emotional go/no-go performance.
C1 [Yerys, Benjamin E.] Childrens Hosp Philadelphia, Ctr Autism Res, Philadelphia, PA 19104 USA.
[Yerys, Benjamin E.; Kenworthy, Lauren; Jankowski, Kathryn F.; Strang, John] Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders, Washington, DC 20010 USA.
[Yerys, Benjamin E.; Kenworthy, Lauren; Jankowski, Kathryn F.; Strang, John] Childrens Natl Med Ctr, Childrens Res Inst, Washington, DC 20010 USA.
[Wallace, Gregory L.] NIMH, Lab Brain & Cognit, Intramural Res Program, Bethesda, MD 20892 USA.
RP Yerys, BE (reprint author), Ctr Autism Res, 3535 Market St,Suite 860, Philadelphia, PA 19104 USA.
EM yerysb@email.chop.edu
OI Jankowski, Kathryn/0000-0003-3096-0814; Wallace,
Gregory/0000-0003-0329-5054
FU Intramural Research Program of the National Institutes of Health,
National Institute of Mental Health; Isadore and Bertha Gudelsky
Foundation; Elizabeth and Frederick Singer Foundation; National
Institute of Mental Health [K23MH086111, R21MH092615]
FX We thank the families for volunteering their time and effort to
participate in our studies. This research was supported in part by the
Intramural Research Program of the National Institutes of Health,
National Institute of Mental Health, Isadore and Bertha Gudelsky
Foundation, the Elizabeth and Frederick Singer Foundation, and the
National Institute of Mental Health Awards K23MH086111 (PI: Benjamin E.
Yerys) and R21MH092615 (PI: Benjamin E. Yerys). We thank Rachel
Weinblatt and Jennifer Sokoloff from the Center for Autism Spectrum
Disorders at Children's National Medical Center for their assistance in
data collection. The content is solely the responsibility of the authors
and does not necessarily represent the official views of the National
Institute of Mental Health or the National Institutes of Health.
NR 43
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U1 6
U2 37
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0894-4105
J9 NEUROPSYCHOLOGY
JI Neuropsychology
PD SEP
PY 2013
VL 27
IS 5
BP 537
EP 545
DI 10.1037/a0033615
PG 9
WC Psychology, Clinical; Neurosciences; Psychology
SC Psychology; Neurosciences & Neurology
GA 212VV
UT WOS:000324011800004
PM 23937480
ER
PT J
AU Wong, SJ
Campbell, B
Massey, B
Lynch, DP
Cohen, EEW
Blair, E
Selle, R
Shklovskaya, J
Jovanovic, BD
Skripkauskas, S
Dew, A
Kulesza, P
Parimi, V
Bergan, RC
Szabo, E
AF Wong, Stuart J.
Campbell, Bruce
Massey, Becky
Lynch, Denis P.
Cohen, Ezra E. W.
Blair, Elizabeth
Selle, Rebecca
Shklovskaya, Julia
Jovanovic, Borko D.
Skripkauskas, Silvia
Dew, Alexander
Kulesza, Peter
Parimi, Vamsi
Bergan, Raymond C.
Szabo, Eva
TI A phase I trial of aminolevulinic acid-photodynamic therapy for
treatment of oral leukoplakia
SO ORAL ONCOLOGY
LA English
DT Article
DE Leukoplakia; Aminolevulinic acid; Photodynamic therapy; Phase I; Laser
ID DYSPLASTIC BARRETTS-ESOPHAGUS; TOPICAL 5-AMINOLEVULINIC ACID;
LIGHT-EMITTING DIODE; VERRUCOUS HYPERPLASIA; EPITHELIAL DYSPLASIA;
INDUCED FLUORESCENCE; CANCER; ERYTHROLEUKOPLAKIA; LESIONS; CAVITY
AB Background: Photodynamic therapy with aminolevulinic acid (ALA PDT) for oral leukoplakia has shown promising effects in regression of oral leukoplakia. Although ALA has been extensively studied and is an ideal photosensitizer, the optimal light dose for treatment of oral leukoplakia has not been determined. We conducted a phase I study to determine MTD and DLT of PDT in patients treated with ALA for leukoplakia.
Methods: Patients with histologically confirmed oral leukoplakia received a single treatment of ALA PDT in cohorts with escalating doses of light (585 nm). Clinical, histologic, and biologic markers were assessed.
Results: Analysis of 11 participants is reported. No significant toxicity from ALA PDT was observed in patients who received ALA with a light dose of up to 4 J/cm(2). One participant experienced transient grade 3 transaminase elevation due to ALA. One participant had a partial clinical response 3 months after treatment. Biologic mucosal risk markers showed no significant associations. Determination of MTD could not be accomplished within a feasible timeframe for completion of the study.
Conclusions: ALA PDT could be safely administered with a light dose up to 4 J/cm(2) and demonstrated activity. Larger studies are needed to fully elucidate the MTD and efficacy of ALA-PDT. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
C1 [Wong, Stuart J.; Campbell, Bruce; Massey, Becky; Selle, Rebecca] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Lynch, Denis P.] Marquette Univ, Sch Dent, Milwaukee, WI 53233 USA.
[Cohen, Ezra E. W.; Blair, Elizabeth] Univ Chicago, Ctr Comprehens Canc, Chicago, IL 60637 USA.
[Bergan, Raymond C.] Northwestern Univ, Ctr Mol Innovat & Drug Discovery, Chicago, IL 60611 USA.
[Szabo, Eva] NCI, Canc Prevent Div, NIH, Chicago, IL USA.
RP Wong, SJ (reprint author), Med Coll Wisconsin, Div Hematol Oncol, Dept Med, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA.
EM swong@mcw.edu
RI Parimi, Vamsi/P-5675-2014;
OI Campbell, Bruce/0000-0001-9485-5728
FU [N01CN35157]
FX Supported by N01CN35157. Stuart Marcus, M. D., Ph. D. (DUSA
Pharmaceuticals, Wilmingham, MA) for supplying agent and device, and
Judy Smith (DCP) for study support.
NR 26
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U1 0
U2 11
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1368-8375
J9 ORAL ONCOL
JI Oral Oncol.
PD SEP
PY 2013
VL 49
IS 9
BP 970
EP 976
DI 10.1016/j.oraloncology.2013.05.011
PG 7
WC Oncology; Dentistry, Oral Surgery & Medicine
SC Oncology; Dentistry, Oral Surgery & Medicine
GA 213HJ
UT WOS:000324046200021
PM 23845699
ER
PT J
AU Huang, YP
Cao, YF
Fang, ZZ
Zhang, YY
Hu, CM
Sun, XY
Yu, ZW
Zhu, X
Hong, M
Yang, L
Sun, HZ
AF Huang, Yin-Peng
Cao, Yun-Feng
Fang, Zhong-Ze
Zhang, Yan-Yan
Hu, Cui-Min
Sun, Xiao-Yu
Yu, Zhen-Wen
Zhu, Xu
Hong, Mo
Yang, Lu
Sun, Hong-Zhi
TI Glycyrrhetinic Acid Exhibits Strong Inhibitory Effects Towards
UDP-Glucuronosyltransferase (UGT) 1A3 and 2B7
SO PHYTOTHERAPY RESEARCH
LA English
DT Article
DE licorice; glycyrrhizic acid; glycyrrhetinic acid;
UDP-glucuronosyltransferases (UGTs); herb-drug interaction
ID DRUG-DRUG INTERACTIONS; HUMAN LIVER; GLUCURONIDATION; POLYMORPHISM;
CELLS
AB The aim of the present study is to evaluate the inhibitory effects of liver UDP-glucuronosyltransferases (UGTs) by glycyrrhizic acid and glycyrrhetinic acid, which are the bioactive ingredients isolated from licorice. The results showed that glycyrrhetinic acid exhibited stronger inhibition towards all the tested UGT isoforms, indicating that the deglycosylation process played an important role in the inhibitory potential towards UGT isoforms. Furthermore, the inhibition kinetic type and parameters were determined for the inhibition of glycyrrhetinic acid towards UGT1A3 and UGT2B7. Data fitting using Dixon and Lineweaver-Burk plots demonstrated that the inhibition of UGT1A3 and UGT2B7 by glycyrrhetinic acid was best fit to competitive and noncompetitive type, respectively. The second plot using the slopes from Lineweaver-Burk plots versus glycyrrhetinic acid concentrations was employed to calculate the inhibition kinetic parameters (K-i), and the values were calculated to be 0.2 and 1.7M for UGT1A3 and UGT2B7, respectively. All these results remind us the possibility of UGT inhibition-based herb-drug interaction. However, the explanation of these in vitro parameters should be paid more caution due to complicated factors, including the probe substrate-dependent UGT inhibition behaviour, environmental factors affecting the abundance of herbs' ingredients, and individual difference of pharmacokinetic factors. Copyright (c) 2012 John Wiley & Sons, Ltd.
C1 [Huang, Yin-Peng; Sun, Hong-Zhi] Liaoning Med Univ, Affiliated Hosp 1, Jinzhou 121001, Peoples R China.
[Cao, Yun-Feng; Fang, Zhong-Ze; Zhang, Yan-Yan; Sun, Xiao-Yu; Yu, Zhen-Wen; Zhu, Xu; Hong, Mo; Yang, Lu; Sun, Hong-Zhi] Chinese Acad Sci, Dalian Inst Chem Phys, Joint Ctr Translat Med, Dalian 116023, Peoples R China.
[Cao, Yun-Feng; Fang, Zhong-Ze; Zhang, Yan-Yan; Sun, Xiao-Yu; Yu, Zhen-Wen; Zhu, Xu; Hong, Mo; Yang, Lu; Sun, Hong-Zhi] Liaoning Med Univ, Affiliated Hosp 1, Dalian 116023, Peoples R China.
[Fang, Zhong-Ze; Hu, Cui-Min] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Sun, HZ (reprint author), Liaoning Med Univ, Affiliated Hosp 1, Jinzhou 121001, Peoples R China.
EM cmushz@163.com
FU National Natural Science Foundation of China [81202586]
FX This work was supported by the National Natural Science Foundation of
China (No. 81202586).
NR 25
TC 11
Z9 13
U1 2
U2 28
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0951-418X
J9 PHYTOTHER RES
JI Phytother. Res.
PD SEP
PY 2013
VL 27
IS 9
BP 1358
EP 1361
DI 10.1002/ptr.4875
PG 4
WC Chemistry, Medicinal; Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 213AB
UT WOS:000324024000016
PM 23148031
ER
PT J
AU Sutin, AR
Costa, PT
Evans, MK
Zonderman, AB
AF Sutin, Angelina R.
Costa, Paul T., Jr.
Evans, Michele K.
Zonderman, Alan B.
TI Personality Assessment in a Diverse Urban Sample
SO PSYCHOLOGICAL ASSESSMENT
LA English
DT Article
DE personality assessment; psychometrics; literacy; Openness to Experience;
socioeconomic status
ID LIFE-SPAN; STABILITY; EDUCATION; TRAITS
AB In the present research, the authors examined the data quality and replicability of the Revised NEO Personality Inventory (NEO-PI-R) factor structure in a sample that varied in ethnicity, socioeconomic status, and literacy. Participants (N = 546), drawn from the Healthy Aging in Neighborhoods of Diversity Across the Life Span study, were African American (58%) and White (42%) urban dwellers living above (49%) and below (51%) 125% of the federal poverty line. The NEO-PI-R, administered via telephone, was evaluated for data quality (percent valid, acquiescence, internal consistency), congruence with the normative factor structure, and readability. All indices of data quality and factor congruence were excellent in the full sample. Literacy was the most consistent predictor of data quality. A slightly worse structure was found for the Openness to Experience and Extraversion factors among lower socioeconomic status African American and White participants. The overall index of factor congruence, however, supports replication of the normative structure well beyond chance levels even among those with lower literacy. Despite the challenges of low literacy, the present findings indicate that personality traits can be assessed reliably in socioeconomically diverse populations that include those living in poverty.
C1 [Sutin, Angelina R.] Florida State Univ, Coll Med, Dept Med Humanities & Social Sci, Tallahassee, FL 32306 USA.
[Sutin, Angelina R.; Costa, Paul T., Jr.; Evans, Michele K.; Zonderman, Alan B.] NIA, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Sutin, AR (reprint author), Florida State Univ, Coll Med, Dept Med Humanities & Social Sci, Tallahassee, FL 32306 USA.
EM angelina.sutin@med.fsu.edu
OI Zonderman, Alan B/0000-0002-6523-4778
FU Intramural NIH HHS [Z99 AG999999]
NR 21
TC 6
Z9 6
U1 1
U2 5
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 1040-3590
J9 PSYCHOL ASSESSMENT
JI Psychol. Assess.
PD SEP
PY 2013
VL 25
IS 3
BP 1007
EP 1012
DI 10.1037/a0032396
PG 6
WC Psychology, Clinical
SC Psychology
GA 212PH
UT WOS:000323994800030
PM 23815114
ER
PT J
AU Keck, TM
Yang, HJ
Bi, GH
Huang, Y
Zhang, HY
Srivastava, R
Gardner, EL
Newman, AH
Xi, ZX
AF Keck, Thomas M.
Yang, Hong-Ju
Bi, Guo-Hua
Huang, Yong
Zhang, Hai-Ying
Srivastava, Ratika
Gardner, Eliot L.
Newman, Amy Hauck
Xi, Zheng-Xiong
TI Fenobam sulfate inhibits cocaine-taking and cocaine-seeking behavior in
rats: implications for addiction treatment in humans
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Cocaine; Fenobam; Self-administration; Reinstatement; Cocaine-seeking
behavior; Incubation of cocaine craving; mGluR5
ID METABOTROPIC GLUTAMATE RECEPTORS; NEGATIVE ALLOSTERIC MODULATORS;
CUE-INDUCED REINSTATEMENT; MGLUR5 ANTAGONIST MPEP; STRESS-INDUCED
RELAPSE; NUCLEUS-ACCUMBENS; DRUG-SEEKING; IN-VIVO; SUBSYNAPTIC
LOCALIZATION; SQUIRREL-MONKEYS
AB Rationale The metabotropic glutamate receptor subtype 5 (mGluR5) has been reported to be critically involved in drug reward and addiction. Because the mGluR5 negative allosteric modulators (NAMs) 2-methyl-6-(phenylethynyl)pyridine (MPEP) and 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP) significantly inhibit addictive like behaviors of cocaine and other drugs of abuse in experimental animals, it has been suggested that mGluR5 NAMs may have translational potential for treatment of addiction in humans. However, neither MPEP nor MTEP have been evaluated in humans due to their off-target actions and rapid metabolism.
Objectives Herein, we evaluate a potential candidate for translational addiction research: a new sulfate salt formulation of fenobam, a selective mGluR5 NAM that has been investigated in humans.
Results In rats, fenobam sulfate had superior pharmacokinetics compared to the free base, with improved maximal plasma concentration (C-max) and longer half life. Oral (p.o.) administration of fenobam sulfate (30 or 60 mg/kg) inhibited intravenous (i.v.) cocaine self-administration, cocaine-induced reinstatement of drug-seeking behavior, and cocaine-associated cue-induced cocaine-seeking behavior in rats. Fenobam sulfate also inhibited p.o. sucrose self-administration and sucrose-induced reinstatement of sucrose-seeking behavior, but had no effect on locomotion.
Conclusions This study provides additional support for the role of mGluR5 signaling in cocaine addiction and suggests that fenobam sulfate may have translational potential in medication development for the treatment of cocaine addiction in humans.
C1 [Keck, Thomas M.; Newman, Amy Hauck] Mol Targets & Medicat Discovery Branch, Med Chem Sect, Baltimore, MD 21224 USA.
[Yang, Hong-Ju; Bi, Guo-Hua; Zhang, Hai-Ying; Srivastava, Ratika; Gardner, Eliot L.; Xi, Zheng-Xiong] NIDA, Neuropsychopharmacol Sect, Chem Biol Res Branch, Intramural Res Program,NIH,DHHS, Baltimore, MD 21224 USA.
[Huang, Yong] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA.
RP Newman, AH (reprint author), Mol Targets & Medicat Discovery Branch, Med Chem Sect, Baltimore, MD 21224 USA.
EM anewman@intra.nida.nih.gov; zxi@mail.nih.gov
RI Keck, Thomas/G-9798-2012;
OI Keck, Thomas/0000-0003-1845-9373; Srivastava,
Rakesh/0000-0002-0065-4069; Zhang, Haiying/0000-0003-0593-5940
FU Intramural Research Program of the National Institute on Drug Abuse,
National Institutes of Health, Department of Health and Human Services;
NIH Postdoctoral Intramural Research Training Associate (IRTA)
Fellowship; NIDA [N01DA-9-8883]
FX This research was supported by the Intramural Research Program of the
National Institute on Drug Abuse, National Institutes of Health,
Department of Health and Human Services. T. M. K. was supported by an
NIH Postdoctoral Intramural Research Training Associate (IRTA)
Fellowship. Pharmacokinetic data was provided under NIDA Contract,
N01DA-9-8883. We thank Drs. Phil Skolnick and Amrat Patel, Division of
Pharmacotherapies and Medical Consequences of Drug Abuse, National
Institute on Drug Abuse, for providing the fenobam free base and fenobam
sulfate, helpful discussions, and critical reading of this manuscript.
NR 66
TC 11
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U1 0
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD SEP
PY 2013
VL 229
IS 2
BP 253
EP 265
DI 10.1007/s00213-013-3106-9
PG 13
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 214OP
UT WOS:000324143700005
PM 23615919
ER
PT J
AU Tanda, G
Li, SM
Mereu, M
Thomas, AM
Ebbs, AL
Chun, LE
Tronci, V
Green, JL
Zou, MF
Kopajtic, TA
Newman, AH
Katz, JL
AF Tanda, Gianluigi
Li, Su Min
Mereu, Maddalena
Thomas, Alexandra M.
Ebbs, Aaron L.
Chun, Lauren E.
Tronci, Valeria
Green, Jennifer L.
Zou, Mu-Fa
Kopajtic, Theresa A.
Newman, Amy Hauck
Katz, Jonathan L.
TI Relations between stimulation of mesolimbic dopamine and place
conditioning in rats produced by cocaine or drugs that are tolerant to
dopamine transporter conformational change
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Dopamine transporter conformation; Accumbens shell; Drug abuse; Dopamine
microdialysis; Place preference; Benztropine analogs; Cocaine
ID UPTAKE INHIBITORS; INTRAVENOUS COCAINE; NUCLEUS-ACCUMBENS;
3-ALPHA-DIPHENYLMETHOXYTROPANE ANALOGS; EXTRACELLULAR DOPAMINE;
BENZTROPINE ANALOGS; IN-VIVO; BINDING; AMPHETAMINE; TRANSMISSION
AB Rationale Dopamine transporter (DAT) conformation plays a role in the effectiveness of cocaine-like and other DAT inhibitors. Cocaine-like stimulants are intolerant to DAT conformation changes having decreased potency in cells transfected with DAT constructs that face the cytosol compared to wild-type DAT. In contrast, analogs of benztropine (BZT) are among compounds that are less affected by DAT conformational change.
Methods We compared the displacement of radioligand binding to various mammalian CNS sites, acute stimulation of accumbens shell dopamine levels, and place conditioning in rats among cocaine and four BZT analogs with Cl substitutions on the diphenyl-ether system including two with carboalkoxy substitutions at the 2-position of the tropane ring.
Results Binding assays confirmed high-affinity and selectivity for the DAT with the BZT analogs which also produced significant stimulation of mesolimbic dopamine efflux. Because BZT analogs produced temporal patterns of extracellular dopamine levels different from those by cocaine (3-10 mg/kg, i.p.), the place conditioning produced by BZT analogs and cocaine was compared at doses and times at which both the increase in dopamine levels and rates of increase were similar to those produced by an effective dose of cocaine. Despite this equilibration, none of the BZT analogs tested produced significant place conditioning.
Conclusions The present results extend previous findings suggesting that cocaine-like actions are dependent on a binding equilibrium that favors the outward conformational state of the DAT. In contrast, BZT analogs with reduced dependence on DAT conformation have reduced cocaine-like behavioral effects and may prove useful in development of medications for stimulant abuse.
C1 [Tanda, Gianluigi; Li, Su Min; Mereu, Maddalena; Thomas, Alexandra M.; Ebbs, Aaron L.; Chun, Lauren E.; Tronci, Valeria; Green, Jennifer L.; Kopajtic, Theresa A.; Katz, Jonathan L.] NIDA, Psychobiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Zou, Mu-Fa; Newman, Amy Hauck] NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Katz, JL (reprint author), NIDA, Psychobiol Sect, Intramural Res Program, NIH, 251 Bayview Blvd,NIDA Suite 200, Baltimore, MD 21224 USA.
EM jkatz@mail.nih.gov
RI Tanda, Gianluigi/B-3318-2009;
OI Tanda, Gianluigi/0000-0001-9526-9878; Katz, Jonathan/0000-0002-1068-1159
FU NIDA Intramural Research Program
FX The present report was funded by NIDA Intramural Research Program.
NR 48
TC 7
Z9 8
U1 1
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD SEP
PY 2013
VL 229
IS 2
BP 307
EP 321
DI 10.1007/s00213-013-3109-6
PG 15
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 214OP
UT WOS:000324143700010
PM 23612854
ER
PT J
AU Phillips, SM
Wojcicki, TR
McAuley, E
AF Phillips, Siobhan M.
Wojcicki, Thomas R.
McAuley, Edward
TI Physical activity and quality of life in older adults: an 18-month panel
analysis
SO QUALITY OF LIFE RESEARCH
LA English
DT Article
DE Physical activity; Quality of life; Self-efficacy; Older adults
ID MAXIMUM-LIKELIHOOD-ESTIMATION; STRUCTURAL EQUATION MODELS;
SELF-EFFICACY; ACTIVITY SCALE; ELDERLY PASE; MISSING DATA; SATISFACTION;
HEALTH; PARTICIPATION; MAINTENANCE
AB Although physical activity has been associated with quality of life (QOL), the empirical evidence regarding the mechanisms underlying this relationship is limited. In the present study, we examined the mediating roles played by self-efficacy and health status in the physical activity-QOL relationship from baseline to 18-month follow-up in a sample of community-dwelling older adults.
Community-dwelling adults (N = 321, M age = 63.8 years) were recruited to participate in a cross-sectional study and were later contacted to participate in an 18-month follow-up. Individuals completed a battery of questionnaires assessing physical activity, self-efficacy, physical self-worth, disability limitations, and quality of life. A panel analysis within a covariance modeling framework was used to analyze the data.
Overall, the model was a good fit to the data (chi(2) = 61.00, df = 29, p < 0.001, standardized root mean residual = 0.05, Comparative Fit Index = 0.97) with changes in physical activity indirectly influencing change in life satisfaction from baseline to 18 months via changes in exercise self-efficacy, physical self-worth, and disability limitations independent of baseline relationships and demographic factors. Specifically, increases in physical activity were associated with increases in exercise self-efficacy which, in turn, was associated with higher physical self-worth and fewer disability limitations which were associated with greater life satisfaction.
The findings from this study suggest the relationship between physical activity and global QOL in older adults may be mediated by more proximal modifiable outcomes that can be targeted in physical activity programs and interventions.
C1 [Phillips, Siobhan M.; Wojcicki, Thomas R.; McAuley, Edward] Univ Illinois, Dept Kinesiol & Community Hlth, Urbana, IL 61801 USA.
[Phillips, Siobhan M.] NCI, Ctr Canc Training, Bethesda, MD 20892 USA.
RP Phillips, SM (reprint author), NCI, Ctr Canc Training, 6120 Execut Blvd,Suite 150E, Bethesda, MD 20892 USA.
EM smphillips19@gmail.com
OI Wojcicki, Thomas/0000-0001-6320-413X
FU National Institute on Aging [AG020118]; University of Illinois Urbana
Champaign
FX This study was funded in part by a grant from the National Institute on
Aging (AG020118) and a Shahid and Ann Carlson Khan Professorship in
Applied Health Sciences at the University of Illinois Urbana Champaign.
NR 43
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U1 2
U2 32
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-9343
J9 QUAL LIFE RES
JI Qual. Life Res.
PD SEP
PY 2013
VL 22
IS 7
BP 1647
EP 1654
DI 10.1007/s11136-012-0319-z
PG 8
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 214BL
UT WOS:000324105100013
PM 23161331
ER
PT J
AU Sarkin, AJ
Groessl, EJ
Carlson, JA
Tally, SR
Kaplan, RM
Sieber, W
Ganiats, TG
AF Sarkin, Andrew J.
Groessl, Erik J.
Carlson, Jordan A.
Tally, Steven R.
Kaplan, Robert M.
Sieber, William J.
Ganiats, Theodore G.
TI Development and validation of a mental health subscale from the Quality
of Well-Being Self-Administered
SO QUALITY OF LIFE RESEARCH
LA English
DT Article
DE QWB-SA; Quality of life; Mental health; Mental illness; Mental health
screening
ID OF-LIFE; MAJOR DEPRESSION; IQOLA PROJECT; SURVEY SF-36; ILLNESS;
SCHIZOPHRENIA; INDEXES; SYSTEM; MODEL; SCALE
AB The purpose of this study was to create and validate a mental health subscale for the Quality of Well-Being Self-Administered (QWB-SA).
The QWB-SA and other measures such as the Profile of Mood States (POMS), Medical Outcomes Study 36 Item Short Form (SF-36), EuroQOL 5D (EQ-5D), and Health Utilities Index Mark 2 (HUI) were administered to three samples: a general population (N = 3,844), a non-psychiatric medical population (N = 535), and a psychiatric population (N = 915). Independent expert ratings of which items represented the construct of mental health were used along with psychometric methods to develop and validate a 10-item QWB-SA mental health scale.
The mental health scale demonstrated high internal consistency (Cronbach's alpha = 0.827-0.842) and strong correlations with other measures of mental health, such as the POMS (r = -0.77), mental health scale from the SF-36 (r = 0.72), EQ-5D mood item (r = 0.61), and HUI Emotion Scale (r = 0.59). It was not highly correlated with measures of physical health. Among the psychiatric population, the new mental health scale was moderately correlated with indicators of psychiatric problem severity.
It is now possible to report outcomes and relationships with mental health in studies that use the QWB-SA. This new mental health subscale can also be used with the large volume of previously collected data using the QWB-SA to examine the impact of illnesses and interventions on mental health-related quality of life.
C1 [Sarkin, Andrew J.; Groessl, Erik J.; Carlson, Jordan A.; Tally, Steven R.; Ganiats, Theodore G.] Univ Calif San Diego, Hlth Serv Res Ctr, La Jolla, CA 92093 USA.
[Sarkin, Andrew J.; Sieber, William J.; Ganiats, Theodore G.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA.
[Kaplan, Robert M.] NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Sarkin, AJ (reprint author), Univ Calif San Diego, Hlth Serv Res Ctr, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM asarkin@ucsd.edu
FU NIA NIH HHS [P01 AG020679]
NR 46
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U1 1
U2 11
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-9343
J9 QUAL LIFE RES
JI Qual. Life Res.
PD SEP
PY 2013
VL 22
IS 7
BP 1685
EP 1696
DI 10.1007/s11136-012-0296-2
PG 12
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 214BL
UT WOS:000324105100017
PM 23104088
ER
PT J
AU Weickert, TW
Mattay, VS
Das, S
Bigelow, LB
Apud, JA
Egan, MF
Weinberger, DR
Goldberg, TE
AF Weickert, Thomas W.
Mattay, Venkata S.
Das, Saumitra
Bigelow, Llewellyn B.
Apud, Jose A.
Egan, Michael F.
Weinberger, Daniel R.
Goldberg, Terry E.
TI Dopaminergic therapy removal differentially effects learning in
schizophrenia and Parkinson's disease
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE Schizophrenia; Parkinson's disease; Frontal-striatal circuitry;
Dopamimetics; Probabilistic association learning; Antipsychotics
ID EMISSION COMPUTERIZED-TOMOGRAPHY; CAUDATE-NUCLEUS; MEMORY-SYSTEMS;
HUNTINGTONS-DISEASE; NEURAL RESPONSES; COGNITIVE SKILL; BASAL GANGLIA;
REWARD; CLASSIFICATION; RECEPTOR
AB Studies of patients with Parkinson's disease receiving dopamimetics report conflicting evidence for early learning of probabilistic cue-outcome associations that elicits frontal-striatal activity. Previous studies of probabilistic association learning in patients with schizophrenia administered antipsychotics have displayed conflicting evidence for normal and abnormal learning. The role of dopaminergic treatment (dopamimetic versus dopamine antagonistic) effects on probabilistic association learning in these diseases that directly impact the dopamine system is not fully understood. The current study examined the effects of dopaminergic therapies on probabilistic association learning in 13 patients with schizophrenia and 8 patients with Parkinson's disease under two conditions: after withdrawal from dopaminergic treatment and following administration of appropriate dopaminergic treatment. Medication order was counterbalanced in both groups. Patients with Parkinson's disease failed to demonstrate any significant improvement over 150 trials, under both conditions (receiving or withdrawn from dopamimetics). Patients with schizophrenia withdrawn from antipsychotics displayed significant improvement during later trials only. These results demonstrate an effect of dopamine (DA) signaling on probabilistic association learning in that: (1) dopamine replacement therapy in Parkinson's disease is insufficient to significantly improve probabilistic association learning and (2) DA receptor blockade impairs and removal of DA receptor blockade significantly improves frontal-striatal-dependent probabilistic association learning in schizophrenia, which is a novel finding and is opposite to the effects shown following removal of DA receptor blockade on other cognitive domains reported previously. Crown Copyright (C) 2013 Published by Elsevier B.V. All rights reserved.
C1 [Weickert, Thomas W.; Mattay, Venkata S.; Das, Saumitra; Bigelow, Llewellyn B.; Apud, Jose A.; Egan, Michael F.; Weinberger, Daniel R.; Goldberg, Terry E.] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
RP Weickert, TW (reprint author), Univ New S Wales, Sch Psychiat, Neurosci Res Australia, Barker St, Randwick, NSW 2031, Australia.
EM t.weickert@unsw.edu.au
FU NIMH; Weinberger Lab.
FX This work was supported by the NIMH Intramural Research Program with
direct funding from the Weinberger Lab. This organization had no further
role in the 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 41
TC 7
Z9 7
U1 0
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD SEP
PY 2013
VL 149
IS 1-3
BP 162
EP 166
DI 10.1016/j.schres.2013.06.028
PG 5
WC Psychiatry
SC Psychiatry
GA 211UQ
UT WOS:000323937200025
PM 23830543
ER
PT J
AU Sadowski, SM
Kebebew, E
AF Sadowski, Samira M.
Kebebew, Electron
TI Which Hemostatic Surgical Devices Should Be Used for Thyroid Surgery, or
Should We Just Continue to Clamp and Tie?
SO THYROID
LA English
DT Editorial Material
ID LIGASURE
C1 [Sadowski, Samira M.; Kebebew, Electron] NCI, Endocrine Oncol Branch, Bethesda, MD 20892 USA.
RP Kebebew, E (reprint author), NCI, Endocrine Oncol Branch, Bldg 10 CRC,Room 3-3940,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA.
EM kebebewe@mail.nih.gov
NR 11
TC 0
Z9 0
U1 0
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
J9 THYROID
JI Thyroid
PD SEP 1
PY 2013
VL 23
IS 9
BP 1047
EP 1048
DI 10.1089/thy.2013.0286
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 213LT
UT WOS:000324059400001
PM 23688251
ER
PT J
AU Bisoffi, Z
Buonfrate, D
Sequi, M
Mejia, R
Cimino, RO
Krolewiecki, AJ
Albonico, M
Gobbo, M
Bonafini, S
Requena-Mendez, A
Munoz, J
Nutman, TB
AF Bisoffi, Z.
Buonfrate, D.
Sequi, M.
Mejia, R.
Cimino, R. O.
Krolewiecki, A. J.
Albonico, M.
Gobbo, M.
Bonafini, S.
Requena-Mendez, A.
Munoz, J.
Nutman, T. B.
TI Comparison of diagnostic accuracy of five serodiagnostic tests for
strongyloidiasis
SO TROPICAL MEDICINE & INTERNATIONAL HEALTH
LA English
DT Meeting Abstract
C1 [Bisoffi, Z.; Buonfrate, D.; Sequi, M.; Albonico, M.; Gobbo, M.; Bonafini, S.] Sacro Cuore Hosp, Ctr Trop Dis, Verona, Italy.
[Mejia, R.; Nutman, T. B.] NIAID, NIH, Bethesda, MD 20892 USA.
[Cimino, R. O.; Krolewiecki, A. J.] Natl Univ Salta, Salta, Argentina.
[Requena-Mendez, A.; Munoz, J.] Univ Barcelona, Hosp Clin, Barcelona Ctr Int Hlth Res CRESIB, E-08007 Barcelona, Spain.
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 1360-2276
J9 TROP MED INT HEALTH
JI Trop. Med. Int. Health
PD SEP
PY 2013
VL 18
SU 1
SI SI
BP 57
EP 57
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 213BS
UT WOS:000324029000145
ER
PT J
AU Clark, C
Bhat, S
Talaat, K
Babu, S
Swaminathan, S
Kumarasamy, N
Nutman, T
AF Clark, C.
Bhat, S.
Talaat, K.
Babu, S.
Swaminathan, S.
Kumarasamy, N.
Nutman, T.
TI Bystander impairment of HIV-specific immune responses by co-incident
filarial (W. bancrofti) infection
SO TROPICAL MEDICINE & INTERNATIONAL HEALTH
LA English
DT Meeting Abstract
C1 [Clark, C.; Nutman, T.] NIAID, NIH, Bethesda, MD 20892 USA.
[Bhat, S.; Babu, S.] NIRT Int Ctr Excellence Res, Natl Inst Hlth, Madras, Tamil Nadu, India.
[Talaat, K.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Swaminathan, S.] Natl Inst Res TB, Chennai, Tamil Nadu, India.
[Kumarasamy, N.] YRG Care, Madras, Tamil Nadu, India.
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 1360-2276
J9 TROP MED INT HEALTH
JI Trop. Med. Int. Health
PD SEP
PY 2013
VL 18
SU 1
SI SI
BP 175
EP 175
PG 1
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 213BS
UT WOS:000324029000473
ER
PT J
AU Steagall, WK
Pacheco-Rodriguez, G
Glasgow, CG
Ikeda, Y
Lin, JP
Zheng, G
Moss, J
AF Steagall, Wendy K.
Pacheco-Rodriguez, Gustavo
Glasgow, Connie G.
Ikeda, Yoshihiko
Lin, Jing-Ping
Zheng, Gang
Moss, Joel
TI Osteoprotegerin Contributes to the Metastatic Potential of Cells with a
Dysfunctional TSC2 Tumor-Suppressor Gene
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID BONE-MINERAL DENSITY; TRAIL-INDUCED APOPTOSIS; KAPPA-B LIGAND; TUBEROUS
SCLEROSIS COMPLEX; CORONARY-ARTERY-DISEASE; PROSTATE-CANCER CELLS;
PULMONARY LYMPHANGIOLEIOMYOMATOSIS; RECEPTOR ACTIVATOR;
ENDOTHELIAL-CELLS; SURVIVAL FACTOR
AB In addition to its effects on bone metabolism, osteoprotegerin (OPG), a soluble member of the tumor necrosis factor family of receptors, promotes smooth muscle cell proliferation and migration and may act as a survival factor for tumor cells. We hypothesized that these cellular mechanisms of OPG may be involved in the growth and proliferation of lymphangioleiomyomatosis (LAM) cells, abnormal smooth muscle-like cells with mutations in one of the tuberous sclerosis complex tumor-suppressor genes (TSC1/TSC2) that cause LAM, a multisystem disease characterized by cystic lung destruction, lymphatic infiltration, and abdominal tumors. Herein, we show that OPG stimulated proliferation of cells cultured from explanted LAM lungs, and selectively induced migration of LAM cells identified by the loss of heterozygosity for TSC2. Consistent with these observations, cells with TSC2 toss of heterozygosity expressed the OPG receptors, receptor activator of NF-kappa B ligand, syndecan-1, and syndecan-2. LAM lung nodules showed reactivities to antibodies to tumor necrosis factor related apoptosis-inducing ligand, receptor activator of NF-kappa B ligand, syndecan-1, and syndecan-2. LAM Lung nodules also produced OPG, as shown by expression of OPG mRNA and colocalization of reactivities to anti-OPG and anti-gp100 (HMB45) antibodies in LAM lung nodules. Serum OPG was significantly higher in LAM patients than in normal volunteers. Based on these data, it appears that OPG may have tumor-promoting roles in the pathogenesis of lymphangioleiomyomatosis, perhaps acting as both autocrine and paracrine factors.
C1 [Steagall, Wendy K.; Pacheco-Rodriguez, Gustavo; Glasgow, Connie G.; Ikeda, Yoshihiko; Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
[Lin, Jing-Ping; Zheng, Gang] NHLBI, Off Biostat Res, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
RP Moss, J (reprint author), NIH, 9000 Rockville Pike,Bldg 10 Room 6D05, Bethesda, MD 20892 USA.
EM mossj@nhlbi.nih.gov
FU Intramural Research Program; NIH; National Heart, Lung, and Blood
Institute; Oak Ridge Institute for Science and Education senior
fellowship
FX Supported by the Intramural Research Program, the NIH, the National
Heart, Lung, and Blood Institute, and an Oak Ridge Institute for Science
and Education senior fellowship (Y.I.).
NR 66
TC 1
Z9 1
U1 0
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD SEP
PY 2013
VL 183
IS 3
BP 938
EP 950
DI 10.1016/j.ajpath.2013.05.024
PG 13
WC Pathology
SC Pathology
GA 210WP
UT WOS:000323866000027
PM 23867796
ER
PT J
AU Lee, D
Vandrey, R
Milman, G
Bergamaschi, M
Mendu, DR
Murray, JA
Barnes, AJ
Huestis, MA
AF Lee, Dayong
Vandrey, Ryan
Milman, Garry
Bergamaschi, Mateus
Mendu, Damodara R.
Murray, Jeannie A.
Barnes, Allan J.
Huestis, Marilyn A.
TI Oral fluid/plasma cannabinoid ratios following controlled oral THC and
smoked cannabis administration
SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY
LA English
DT Article
DE Cannabis; Marijuana; Delta9-tetrahydrocannabinol; Oral fluid; Plasma;
Ratio
ID 2-DIMENSIONAL GAS-CHROMATOGRAPHY; MOTOR-VEHICLE CRASHES; SIMULTANEOUS
QUANTIFICATION; PHARMACOKINETIC PROPERTIES; MASS-SPECTROMETRY;
WHOLE-BLOOD; FLUID; PLASMA; DELTA(9)-TETRAHYDROCANNABINOL; DRUGS
AB Oral fluid (OF) is a valuable biological alternative for clinical and forensic drug testing. Evaluating OF to plasma (OF/P) cannabinoid ratios provides important pharmacokinetic data on the disposition of drug and factors influencing partition between matrices. Eleven chronic cannabis smokers resided on a closed research unit for 51 days. There were four 5-day sessions of 0, 30, 60, and 120 mg oral a dagger(9)-tetrahydrocannabinol (THC)/day followed by a five-puff smoked cannabis challenge on Day 5. Each session was separated by 9 days ad libitum cannabis smoking. OF and plasma specimens were analyzed for THC and metabolites. During ad libitum smoking, OF/P THC ratios were high (median, 6.1; range, 0.2-348.5) within 1 h after last smoking, decreasing to 0.1-20.7 (median, 2.1) by 13.0-17.1 h. OF/P THC ratios also decreased during 5-days oral THC dosing, and after the smoked cannabis challenge, median OF/P THC ratios decreased from 1.4 to 5.5 (0.04-245.6) at 0.25 h to 0.12 to 0.17 (0.04-5.1) at 10.5 h post-smoking. In other studies, longer exposure to more potent cannabis smoke and oromucosal cannabis spray was associated with increased OF/P THC peak ratios. Median OF/P 11-nor-9-carboxy-THC (THCCOOH) ratios were 0.3-2.5 (range, 0.1-14.7) ng/mu g, much more consistent in various dosing conditions over time. OF/P THC, but not THCCOOH, ratios were significantly influenced by oral cavity contamination after smoking or oromucosal spray of cannabinoid products, followed by time-dependent decreases. Establishing relationships between OF and plasma cannabinoid concentrations is essential for making inferences of impairment or other clinical outcomes from OF concentrations.
C1 [Lee, Dayong; Milman, Garry; Bergamaschi, Mateus; Mendu, Damodara R.; Barnes, Allan J.; Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
[Vandrey, Ryan; Murray, Jeannie A.] Johns Hopkins Univ, Sch Med, Behav Biol Res Ctr, Baltimore, MD 21224 USA.
RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, Biomed Res Ctr, 251 Bayview Blvd Suite 200, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU National Institute on Drug Abuse [R01 DA025044]; National Institute on
Drug Abuse, NIH
FX This research was funded by grant R01 DA025044 from the National
Institute on Drug Abuse and by the Intramural Research Program, National
Institute on Drug Abuse, NIH. The funding sources had no role in study
design, data collection and analysis, or presentation of results. This
study was registered on clinicaltrials.gov (NCT00893074).
NR 37
TC 12
Z9 12
U1 2
U2 35
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1618-2642
J9 ANAL BIOANAL CHEM
JI Anal. Bioanal. Chem.
PD SEP
PY 2013
VL 405
IS 23
BP 7269
EP 7279
DI 10.1007/s00216-013-7159-8
PG 11
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 208CJ
UT WOS:000323653400012
PM 23831756
ER
PT J
AU Arem, H
Mayne, ST
Sampson, J
Risch, H
Stolzenberg-Solomon, RZ
AF Arem, Hannah
Mayne, Susan T.
Sampson, Joshua
Risch, Harvey
Stolzenberg-Solomon, Rachael Z.
TI Dietary fat intake and risk of pancreatic cancer in the Prostate, Lung,
Colorectal and Ovarian Cancer Screening Trial
SO ANNALS OF EPIDEMIOLOGY
LA English
DT Article
DE Dietary fats; Cohort studies; Pancreatic neoplasms; Epidemiology
ID FUNCTIONAL DYSPEPSIA; CARCINOGENESIS; MEAT; SMOKING; INSULIN; SMOKERS;
MODELS; COHORT; HEALTH; ACIDS
AB Purpose: Epidemiologic and experimental studies suggest that dietary fat intake may affect risk of pancreatic cancer, but published results are inconsistent.
Methods: We examined risk associations for specific types of dietary fat intakes and related food sources among 111,416 participants in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We used Cox proportional hazards regression to examine associations between fat intake and pancreatic cancer risk.
Results: Over a mean 8.4 years of follow-up, 411 pancreatic cancer cases were identified. We observed an inverse association between saturated fat intake and pancreatic cancer risk (hazard ratio [HR], 0.64 comparing extreme quintiles; 95% confidence interval [CI], 0.46-0.88), but the association became weaker and nonsignificant when individuals with fewer than 4 years of follow-up were excluded to avoid possible reverse causation (HR, 0.88; 95% CI, 0.58-1.33). Total fat intake showed a similar pattern of association, whereas intakes of monounsaturated and polyunsaturated fats and fats from animal or plant sources showed no associations with risk.
Conclusions: These results do not support the hypothesis of increased pancreatic cancer risk with higher fat consumption overall or by specific fat type or source. Dietary changes owing to undetected disease may explain the observed inverse association with saturated fat. Published by Elsevier Inc.
C1 [Arem, Hannah; Mayne, Susan T.; Risch, Harvey] Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT USA.
[Arem, Hannah; Sampson, Joshua; Stolzenberg-Solomon, Rachael Z.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Mayne, Susan T.; Risch, Harvey] Yale Canc Ctr, New Haven, CT USA.
RP Arem, H (reprint author), NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, 9609 Med Ctr Dr,Room 6E324, Bethesda, MD 20892 USA.
EM aremhe2@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute; Division of Cancer Prevention, National
Cancer Institute, National Institutes of Health, DHHS; [T32 CA105666]
FX This work was supported in part by the training grant T32 CA105666. This
research was also supported in part by the Intramural Research Program
of the National Institutes of Health, National Cancer Institute. This
research was supported by contracts from the Division of Cancer
Prevention, National Cancer Institute, National Institutes of Health,
DHHS. The authors thank Drs. Christine Berg and Philip Prorok, Division
of Cancer Prevention, National Cancer Institute, the Screening Center
investigators and staff of the Prostate, Lung, Colorectal, and Ovarian
(PLCO) Cancer Screening Trial, Mr. Tom Riley and staff, Information
Management Services, Inc., Ms. Barbara O'Brien and staff, Westat, Inc.
Most important, we acknowledge the study participants for their
contributions to making this study possible.
NR 31
TC 9
Z9 10
U1 0
U2 17
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1047-2797
J9 ANN EPIDEMIOL
JI Ann. Epidemiol.
PD SEP
PY 2013
VL 23
IS 9
BP 571
EP 575
DI 10.1016/j.annepidem.2013.06.006
PG 5
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 210TE
UT WOS:000323856700008
PM 23890797
ER
PT J
AU Kamper-Jorgensen, M
Rostgaard, K
Glaser, SL
Zahm, SH
Cozen, W
Smedby, KE
Sanjose, S
Chang, ET
Zheng, T
La Vecchia, C
Serraino, D
Monnereau, A
Kane, EV
Miligi, L
Vineis, P
Spinelli, JJ
McLaughlin, JR
Pahwa, P
Dosman, JA
Vornanen, M
Foretova, L
Maynadie, M
Staines, A
Becker, N
Nieters, A
Brennan, P
Boffetta, P
Cocco, P
Hjalgrim, H
AF Kamper-Jorgensen, M.
Rostgaard, K.
Glaser, S. L.
Zahm, S. H.
Cozen, W.
Smedby, K. E.
Sanjose, S.
Chang, E. T.
Zheng, T.
La Vecchia, C.
Serraino, D.
Monnereau, A.
Kane, E. V.
Miligi, L.
Vineis, P.
Spinelli, J. J.
McLaughlin, J. R.
Pahwa, P.
Dosman, J. A.
Vornanen, M.
Foretova, L.
Maynadie, M.
Staines, A.
Becker, N.
Nieters, A.
Brennan, P.
Boffetta, P.
Cocco, P.
Hjalgrim, H.
TI Cigarette smoking and risk of Hodgkin lymphoma and its subtypes: a
pooled analysis from the International Lymphoma Epidemiology Consortium
(InterLymph)
SO ANNALS OF ONCOLOGY
LA English
DT Review
DE Hodgkin lymphoma; case-control; cigarette smoking; epidemiology;
Epstein-Barr virus; individual patient data meta-analysis
ID CHILDHOOD SOCIAL-ENVIRONMENT; SOFT-TISSUE SARCOMA; ALCOHOL-DRINKING;
INFECTIOUS-MONONUCLEOSIS; SOCIOECONOMIC-STATUS; LOGISTIC-REGRESSION;
MALIGNANT-LYMPHOMAS; TOBACCO SMOKING; UNITED-STATES; FOLLOW-UP
AB The etiology of Hodgkin lymphoma (HL) remains incompletely characterized. Studies of the association between smoking and HL have yielded ambiguous results, possibly due to differences between HL subtypes.
Through the InterLymph Consortium, 12 case-control studies regarding cigarette smoking and HL were identified. Pooled analyses on the association between smoking and HL stratified by tumor histology and Epstein-Barr virus (EBV) status were conducted using random effects models adjusted for confounders. Analyses included 3335 HL cases and 14 278 controls.
Overall, 54.5% of cases and 57.4% of controls were ever cigarette smokers. Compared with never smokers, ever smokers had an odds ratio (OR) of HL of 1.10 [95% confidence interval (CI) 1.01-1.21]. This increased risk reflected associations with mixed cellularity cHL (OR = 1.60, 95% CI 1.29-1.99) and EBV-positive cHL (OR = 1.81, 95% CI 1.27-2.56) among current smokers, whereas risk of nodular sclerosis (OR = 1.09, 95% CI 0.90-1.32) and EBV-negative HL (OR = 1.02, 95% CI 0.72-1.44) was not increased.
These results support the notion of etiologic heterogeneity between HL subtypes, highlighting the need for HL stratification in future studies. Even if not relevant to all subtypes, our study emphasizes that cigarette smoking should be added to the few modifiable HL risk factors identified.
C1 [Kamper-Jorgensen, M.] Univ Copenhagen, Dept Publ Hlth, DK-1014 Copenhagen K, Denmark.
[Kamper-Jorgensen, M.; Rostgaard, K.; Hjalgrim, H.] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark.
[Glaser, S. L.] Canc Prevent Inst Calif, Dept Res, Fremont, CA USA.
[Zahm, S. H.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Cozen, W.] Univ So Calif, Dept Prevent Med & Pathol, Los Angeles, CA USA.
[Smedby, K. E.] Karolinska Inst, Unit Clin Epidemiol, Dept Med, Stockholm, Sweden.
[Sanjose, S.] Inst Catala Oncol, Unit Infect & Canc, Barcelona, Spain.
[Chang, E. T.] Exponent Inc, Hlth Sci Practice, Menlo Pk, CA USA.
[Glaser, S. L.; Chang, E. T.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
[Foretova, L.] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic.
[La Vecchia, C.] Ist Ric Farmacol Mario Negri IRCCS, Dept Epidemiol, Chieti, Italy.
[La Vecchia, C.] Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy.
[Serraino, D.] IRCCS Ctr Riferimento Oncol, Sci Directorate, Epidemiol & Biostatist Unit, Aviano, Italy.
[Monnereau, A.] Ctr Res Epidemiol & Populat Hlth CESP, INSERM, Environmental Epidemiol Canc Grp, U1018, Villejuif, France.
[Monnereau, A.] Registry Hematol Malignancies Gironde, Dept Clin Res & Med Informat, Bergonie Inst, Bordeaux, France.
[Miligi, L.] ISPO Canc Prevent & Res Inst, Environm & Occupat Epidemiol Unit, Florence, Italy.
[Vineis, P.] Univ London Imperial Coll Sci Technol & Med, London, England.
[Spinelli, J. J.] BC Canc Agcy, Vancouver, BC, Canada.
[Spinelli, J. J.] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC V5Z 1M9, Canada.
[McLaughlin, J. R.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[McLaughlin, J. R.] Mt Sinai Hosp Joseph & Wolf Lebov Hlth Complex, Samuel Lunenfeld Res Inst, Toronto, ON, Canada.
[Pahwa, P.] Univ Saskatchewan, Dept Community Hlth & Epidemiol, Saskatoon, SK, Canada.
[Zheng, T.] Yale Univ, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA.
[Becker, N.] German Canc Res Ctr, Dept Canc Epidemiol, Heidelberg, Germany.
[Cocco, P.] Univ Cagliari, Dept Publ Hlth, Monserrato, Italy.
[Nieters, A.] Univ Freiburg Klinikum, Dept Canc Epidemiol & Genet, Freiburg, Germany.
[Maynadie, M.] Univ Burgundy, Registre Hemopathies Malignes Cote Or EA4184, Dijon, France.
[Maynadie, M.] Univ Hosp, Dijon, France.
[Brennan, P.] Int Agcy Res Canc, Genet Sect, F-69372 Lyon, France.
[Boffetta, P.] Mt Sinai Sch Med, Tisch Canc Inst & Inst Translat Epidemiol, New York, NY USA.
[Boffetta, P.] Int Prevent Res Inst, Lyon, France.
[Vornanen, M.] Fimlab Labs, Dept Pathol, Tampere, Finland.
RP Kamper-Jorgensen, M (reprint author), Univ Copenhagen, Dept Publ Hlth, Oster Farimagsgade 5,Postbox 2099, DK-1014 Copenhagen K, Denmark.
EM maka@sund.ku.dk
RI Spinelli, John/B-6210-2013; Monnereau, Alain/L-1249-2014;
OI Monnereau, Alain/0000-0002-5056-1397; Kamper-Jorgensen,
Mads/0000-0001-6393-5258; Staines, Anthony/0000-0001-9161-1357;
Serraino, Diego/0000-0003-0565-8920; La Vecchia,
Carlo/0000-0003-1441-897X; Rostgaard, Klaus/0000-0001-6220-9414
FU NIH [5 ROI CA 69269]; Nordic Cancer Union; Plan Danmark [16-02-D];
Italian Association for Cancer Research
FX The study was supported by NIH (grant number 5 ROI CA 69269), Nordic
Cancer Union (no grant number), Plan Danmark grant number is 16-02-D,
and the Italian Association for Cancer Research (no grant number).
NR 60
TC 11
Z9 11
U1 0
U2 12
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
J9 ANN ONCOL
JI Ann. Oncol.
PD SEP
PY 2013
VL 24
IS 9
BP 2245
EP 2255
DI 10.1093/annonc/mdt218
PG 11
WC Oncology
SC Oncology
GA 212DT
UT WOS:000323963100006
PM 23788758
ER
PT J
AU Ando, H
Sato, T
Tomaru, U
Yoshida, M
Utsunomiya, A
Yamauchi, J
Araya, N
Yagishita, N
Coler-Reilly, A
Shimizu, Y
Yudoh, K
Hasegawa, Y
Nishioka, K
Nakajima, T
Jacobson, S
Yamano, Y
AF Ando, Hitoshi
Sato, Tomoo
Tomaru, Utano
Yoshida, Mari
Utsunomiya, Atae
Yamauchi, Junji
Araya, Natsumi
Yagishita, Naoko
Coler-Reilly, Ariella
Shimizu, Yukiko
Yudoh, Kazuo
Hasegawa, Yasuhiro
Nishioka, Kusuki
Nakajima, Toshihiro
Jacobson, Steven
Yamano, Yoshihisa
TI Positive feedback loop via astrocytes causes chronic inflammation in
virus-associated myelopathy
SO BRAIN
LA English
DT Article
DE HTLV-1; HAM/TSP; CXCL10; CXCR3; astrocyte
ID I-ASSOCIATED MYELOPATHY; T-CELL LEUKEMIA; TROPICAL SPASTIC PARAPARESIS;
SPINAL-CORD LESIONS; HTLV-I; PROVIRAL LOAD; PERIPHERAL-BLOOD; CYTOKINE
EXPRESSION; MONONUCLEAR-CELLS; INTERFERON-GAMMA
AB Human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a rare neurodegenerative disease characterized by chronic inflammation in the spinal cord. We hypothesized that a positive feedback loop driven by chemokines may be responsible for the chronic inflammation in HAM/TSP. We aimed to determine the identity of these chemokines, where they are produced, and how they drive chronic inflammation in HAM/TSP. We found that patients with HAM/TSP have extraordinarily high levels of the chemokine CXCL10 (also known as IP-10) and an abundance of cells expressing the CXCL10-binding receptor CXCR3 in the cerebrospinal fluid. Histological analysis revealed that astrocytes are the main producers of CXCL10 in the spinal cords of patients with HAM/TSP. Co-culture of human astrocytoma cells with CD4(+) T cells from patients with HAM/TSP revealed that astrocytes produce CXCL10 in response to IFN-gamma secreted by CD4(+) T cells. Chemotaxis assays results suggest that CXCL10 induces migration of peripheral blood mononuclear cells to the central nervous system and that anti-CXCL10 neutralizing antibody can disrupt this migration. In short, we inferred that human T-lymphotropic virus type 1-infected cells in the central nervous system produce IFN-gamma that induces astrocytes to secrete CXCL10, which recruits more infected cells to the area via CXCR3, constituting a T helper type 1-centric positive feedback loop that results in chronic inflammation.
C1 [Ando, Hitoshi; Sato, Tomoo; Yamauchi, Junji; Araya, Natsumi; Yagishita, Naoko; Coler-Reilly, Ariella; Shimizu, Yukiko; Yamano, Yoshihisa] St Marianna Univ, Sch Med, Inst Med Sci, Dept Rare Dis Res, Kawasaki, Kanagawa 2168512, Japan.
[Tomaru, Utano] Hokkaido Univ, Grad Sch Med, Dept Pathol, Sapporo, Hokkaido, Japan.
[Yoshida, Mari] Aichi Med Univ, Inst Med Sci Ageing, Aichi, Japan.
[Utsunomiya, Atae] Imamura Bun In Hosp, Dept Haematol, Kagoshima, Japan.
[Yudoh, Kazuo] St Marianna Univ, Sch Med, Inst Med Sci, Kawasaki, Kanagawa 2168512, Japan.
[Hasegawa, Yasuhiro] St Marianna Univ, Sch Med, Dept Neurol, Kawasaki, Kanagawa 2168512, Japan.
[Nishioka, Kusuki; Nakajima, Toshihiro] Tokyo Med Univ, Inst Med Sci, Tokyo 1608402, Japan.
[Jacobson, Steven] NIH, Viral Immunol Sect, Neuroimmunol Branch, Bethesda, MD 20892 USA.
RP Yamano, Y (reprint author), St Marianna Univ, Sch Med, Inst Med Sci, Dept Rare Dis Res,Miyamae Ku, 2-16-1 Sugao, Kawasaki, Kanagawa 2168512, Japan.
EM yyamano@marianna-u.ac.jp
FU project "Research on Measures for Intractable Disease"; Ministry of
Health Labour and Welfare; Ministry of Education, Culture, Sports,
Science and Technology; MEXT
FX This work was partly supported by project "Research on Measures for
Intractable Disease," a matching fund subsidy from the Ministry of
Health Labour and Welfare, a Grant-in-Aid for Scientific Research from
the Ministry of Education, Culture, Sports, Science and Technology, and
the MEXT-Supported Program for the Strategic Research Foundation at
Private Universities, 2008-2012.
NR 55
TC 17
Z9 17
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
J9 BRAIN
JI Brain
PD SEP
PY 2013
VL 136
BP 2876
EP 2887
DI 10.1093/brain/awt183
PN 9
PG 12
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 212EM
UT WOS:000323965100024
PM 23892452
ER
PT J
AU Wu, T
Hallett, M
AF Wu, Tao
Hallett, Mark
TI Reply: The cerebellum in Parkinson's disease and parkinsonism in
cerebellar disorders
SO BRAIN
LA English
DT Letter
ID SCA2 PARKINSONISM
C1 [Wu, Tao] Capital Med Univ, Beijing Inst Geriatr, Key Lab Neurodegenerat Disorders, Dept Neurobiol,Minist Educ,Xuanwu Hosp, Beijing 100053, Peoples R China.
[Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA.
RP Wu, T (reprint author), Capital Med Univ, Beijing Inst Geriatr, Key Lab Neurodegenerat Disorders, Dept Neurobiol,Minist Educ,Xuanwu Hosp, Beijing 100053, Peoples R China.
EM wutao69@gmail.com
NR 8
TC 3
Z9 3
U1 0
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
J9 BRAIN
JI Brain
PD SEP
PY 2013
VL 136
BP E249
EP U18
DI 10.1093/brain/awt100
PN 9
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 212EM
UT WOS:000323965100004
PM 23739172
ER
PT J
AU Li, WQ
Park, Y
Wu, JW
Ren, JS
Goldstein, AM
Taylor, PR
Hollenbeck, AR
Freedman, ND
Abnet, CC
AF Li, Wen-Qing
Park, Yikyung
Wu, Jennifer W.
Ren, Jian-Song
Goldstein, Alisa M.
Taylor, Philip R.
Hollenbeck, Albert R.
Freedman, Neal D.
Abnet, Christian C.
TI Index-based Dietary Patterns and Risk of Esophageal and Gastric Cancer
in a Large Cohort Study
SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Article
DE Food Habits; Esophageal Neoplasms; Stomach Neoplasms
ID SQUAMOUS-CELL CARCINOMA; MEDITERRANEAN DIET; NATIONAL INSTITUTES;
VEGETABLE INTAKE; QUALITY SCORES; ADENOCARCINOMA; POPULATION; FRUIT;
INFLAMMATION; CONSUMPTION
AB BACKGROUND & AIMS: Diet could affect risk for esophageal and gastric cancers, but associations have been inconsistent. The diet is complex, so studies of dietary patterns, rather than studies of individual foods, might be more likely to identify cancer risk factors. There is limited research on index-based dietary patterns and esophageal and gastric cancers. We prospectively evaluated associations between the Healthy Eating Index-2005 (HEI-2005) and alternate Mediterranean Diet (aMED) scores and risk of esophageal and gastric cancers.
METHODS: We analyzed data from 494,968 participants in the National Institutes of Health-AARP Diet and Health study, in which AARP members (age, 51-70 y) completed a self-administered baseline food frequency questionnaire between 1995 and 1996. Their answers were used to estimate scores for each index.
RESULTS: During the follow-up period (1995-2006), participants developed 215 esophageal squamous cell carcinomas (ESCCs), 633 esophageal adenocarcinomas (EACs), 453 gastric cardia adenocarcinomas, and 501 gastric noncardia adenocarcinomas. Higher scores from the HEI-2005 were associated with a reduced risk of ESCC (comparing the highest quintile with the lowest quintile: hazard ratio, 0.51; 95% confidence interval, 0.31-0.86; P-trend = .001) and EAC (hazard ratio, 0.75; 95% confidence interval, 0.57-0.98; P-trend = .01). We observed an inverse association between ESCC, but not EAC, and a higher aMED score (meaning a higher-quality diet). HEI-2005 and aMED scores were not associated significantly with gastric cardia or noncardia adenocarcinomas.
CONCLUSIONS: By using data collected from 1995 through 2006 from the National Institutes of Health-AARP Diet and Health Study, HEI-2005 and aMED scores were associated inversely with risk for esophageal cancers, particularly ESCC. Adherence to dietary recommendations might help prevent esophageal cancers.
C1 [Li, Wen-Qing; Goldstein, Alisa M.; Taylor, Philip R.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20850 USA.
[Park, Yikyung; Wu, Jennifer W.; Ren, Jian-Song; Freedman, Neal D.; Abnet, Christian C.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20850 USA.
[Hollenbeck, Albert R.] AARP, Washington, DC USA.
RP Li, WQ (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
EM liw9@mail.nih.gov
RI Li, Wenqing/N-2293-2014; Abnet, Christian/C-4111-2015; Freedman,
Neal/B-9741-2015;
OI Li, Wenqing/0000-0002-1283-4091; Abnet, Christian/0000-0002-3008-7843;
Freedman, Neal/0000-0003-0074-1098; Park, Yikyung/0000-0002-6281-489X
FU National Cancer Institute, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health. The study
sponsor was not involved in the study design, data collection, data
analysis, manuscript writing, or review.
NR 28
TC 17
Z9 18
U1 0
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1542-3565
J9 CLIN GASTROENTEROL H
JI Clin. Gastroenterol. Hepatol.
PD SEP
PY 2013
VL 11
IS 9
BP 1130
EP U136
DI 10.1016/j.cgh.2013.03.023
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 210FU
UT WOS:000323816100018
PM 23591281
ER
PT J
AU Hernaez, R
McLean, J
Lazo, M
Brancati, FL
Hirschhorn, JN
Borecki, IB
Harris, TB
Nguyen, T
Kamel, IR
Bonekamp, S
Eberhardt, MS
Clark, JM
Kao, WHL
Speliotes, EK
AF Hernaez, Ruben
McLean, Jody
Lazo, Mariana
Brancati, Frederick L.
Hirschhorn, Joel N.
Borecki, Ingrid B.
Harris, Tamara B.
Thutrang Nguyen
Kamel, Ihab R.
Bonekamp, Susanne
Eberhardt, Mark S.
Clark, Jeanne M.
Kao, Wen Hong Linda
Speliotes, Elizabeth K.
CA Genetics Obesity-Related Liver Dis
TI Association Between Variants in or Near PNPLA3, GCKR, and PPP1R3B With
Ultrasound-Defined Steatosis Based on Data From the Third National
Health and Nutrition Examination Survey
SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Article
DE Nonalcoholic Fatty Liver Disease; Replication; Candidate Gene Study;
Genome-wide Association Study; SNP
ID FATTY LIVER-DISEASE; GENOME-WIDE ASSOCIATION; US ADULTS; SUSCEPTIBILITY
LOCI; METABOLIC SYNDROME; FASTING GLUCOSE; IDENTIFIES LOCI; PREVALENCE;
METAANALYSIS; GLYCOGEN
AB BACKGROUND & AIMS: A genome-wide association study associated 5 genetic variants with hepatic steatosis (identified by computerized tomography) in individuals of European ancestry. We investigated whether these variants were associated with measures of hepatic steatosis (HS) in non-Hispanic white (NHW), non-Hispanic black, and Mexican American (MA) participants in the US population-based National Health and Nutrition Examination Survey III, phase 2.
METHODS: We analyzed data from 4804 adults (1825 NHW, 1442 non-Hispanic black, and 1537 MA; 51.7% women; mean age at examination, 42.5 y); the weighted prevalence of HS was 37.3%. We investigated whether ultrasound-measured HS, with and without increased levels of alanine aminotransferase (ALT), or level of ALT alone, was associated with rs738409 (patatin-like phospholipase domain-containing protein 3 [PNPLA3]), rs2228603 (neurocan [NCAN]), rs12137855 (lysophospholipase-like 1), rs780094 (glucokinase regulatory protein [GCKR]), and rs4240624 (protein phosphatase 1, regulatory subunit 3b [PPP1R3B]) using regression modeling in an additive genetic model, controlling for age, age-squared, sex, and alcohol consumption.
RESULTS: The G allele of rs738409 (PNPLA3) and the T allele of rs780094 (GCKR) were associated with HS with a high level of ALT (odds ratio [OR], 1.36; P = .01; and OR, 1.30; P = .03, respectively). The A allele of rs4240624 (PPP1R3B) and the T allele of rs2228603 (NCAN) were associated with HS (OR, 1.28; P = .03; and OR, 1.40; P = .04, respectively). Variants of PNPLA3 and NCAN were associated with ALT level among all 3 ancestries. Some single-nucleotide polymorphisms were associated with particular races or ethnicities: variants in PNPLA3, NCAN, GCKR, and PPP1R3B were associated with NHW and variants in PNPLA3 were associated with MA. No variants were associated with NHB.
CONCLUSIONS: We used data from the National Health and Nutrition Examination Survey III to validate the association between rs738409 (PNPLA3), rs780094 (GCKR), and rs4240624 (PPP1R3B) with HS, with or without increased levels of ALT, among 3 different ancestries. Some, but not all, associations between variants in NCAN, lysophospholipase-like 1, GCKR, and PPP1R3B with HS (with and without increased ALT level) were significant within subpopulations.
C1 [Hernaez, Ruben; Lazo, Mariana; Brancati, Frederick L.; Clark, Jeanne M.] Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA.
[Kamel, Ihab R.; Bonekamp, Susanne] Johns Hopkins Sch Med, Dept Radiol, Baltimore, MD USA.
[Hernaez, Ruben; Lazo, Mariana; Brancati, Frederick L.; Clark, Jeanne M.; Kao, Wen Hong Linda] Johns Hopkins Univ, Dept Epidemiol, Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Brancati, Frederick L.; Clark, Jeanne M.; Kao, Wen Hong Linda] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
[Hernaez, Ruben] Georgetown Univ Hosp, Washington Hosp Ctr, Dept Med, Washington, DC 20007 USA.
[McLean, Jody] NOVA Res Co, Bethesda, MD USA.
[Hirschhorn, Joel N.; Thutrang Nguyen] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Hirschhorn, Joel N.; Thutrang Nguyen] Childrens Hosp, Div Genet, Boston, MA 02115 USA.
[Hirschhorn, Joel N.; Thutrang Nguyen] Childrens Hosp, Program Genom, Boston, MA 02115 USA.
[Hirschhorn, Joel N.; Thutrang Nguyen; Speliotes, Elizabeth K.] Broad Inst, Cambridge, MA USA.
[Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
[Harris, Tamara B.] NIH, Natl Inst Aging, Intramural Res Program, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Eberhardt, Mark S.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA.
[Speliotes, Elizabeth K.] Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA.
[Speliotes, Elizabeth K.] Univ Michigan, Ctr Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.
RP Speliotes, EK (reprint author), Univ Michigan, 6520 MSRBI,SPC 5682,1150 W Med Ctr Dr, Ann Arbor, MI 48109 USA.
EM espeliot@med.umich.edu
RI Hernaez, Ruben/C-4039-2014;
OI Hernaez, Ruben/0000-0002-1518-4020; Bonekamp,
Susanne/0000-0001-5847-5656
FU American Diabetes Association [7-07-MN-08]; Doris Duke Medical
Foundation; National Institutes of Health [K23DK080145-01, R01DK075787,
5R01DK075681, R01 DK083393]
FX Supported by the American Diabetes Association Mentor-Based Fellowship
Program 7-07-MN-08 (R.H., M.L., F.L.B.), Doris Duke Medical Foundation
(E.K.S.), National Institutes of Health grants K23DK080145-01 (E.K.S.),
R01DK075787 (J.N.H.), 5R01DK075681 (I.B.B.), and R01 DK083393 (J.M.C.,
R.H., M.L., F.L.B., I.R.H., S.B., W.H.L.K.).
NR 32
TC 35
Z9 37
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1542-3565
J9 CLIN GASTROENTEROL H
JI Clin. Gastroenterol. Hepatol.
PD SEP
PY 2013
VL 11
IS 9
BP 1183
EP U203
DI 10.1016/j.cgh.2013.02.011
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 210FU
UT WOS:000323816100027
PM 23416328
ER
PT J
AU Lukacs, B
Cornu, JN
Aout, M
Tessier, N
Hodee, C
Haab, F
Cussenot, O
Merliere, Y
Moysan, V
Vicaut, E
AF Lukacs, Bertrand
Cornu, Jean-Nicolas
Aout, Mounir
Tessier, Natacha
Hodee, Christophe
Haab, Francois
Cussenot, Olivier
Merliere, Yvon
Moysan, Veronique
Vicaut, Eric
TI Management of Lower Urinary Tract Symptoms Related to Benign Prostatic
Hyperplasia in Real-life Practice in France: A Comprehensive Population
Study
SO EUROPEAN UROLOGY
LA English
DT Article
DE 5 alpha-Reductase inhibitors; alpha(1)-Blockers; Benign prostatic
obstruction; Claim database; Epidemiology; Phytotherapy; Population
study
ID TRIUMPH PROJECT; SAW PALMETTO; PRIMARY-CARE; MEN; GUIDELINES; THERAPY;
PREVALENCE; PATTERNS; BPH; AUA
AB Background: Male lower urinary tract symptoms (LUTS) are one of the most treated diseases, but little is known about patient trajectories in current clinical practice.
Objective: To describe the dynamic treatment patterns of LUTS presumably due to benign prostatic obstruction (BPO).
Design, settings, and participants: All prescriptions of alpha(1)-adrenergic receptor blocking agents (alpha(1)-blockers), 5 alpha-reductase inhibitors (5-ARIs), and phytotherapy, and all surgeries related to BPO performed in France from 2004 to 2008 were identified using two distinct administrative claim databases maintained by the National Health Insurance system that covers the entire population. After linking the two data sets, all consecutive treatment events were analyzed for each patient.
Outcome measurements and statistical analysis: Drug prescription details were assessed for each year, region, and prescriber qualification. Medical treatment initiation, interruption, evolution, and events after surgical management (hospital stay, reoperation, complication rates, and subsequent medical prescriptions) were also investigated.
Results and limitations: Overall, 2 620 269 patients were treated within 5 yr, with important geographic variations. Medical treatment was interrupted for approximately 16% of patients. The alpha(1)-blockers were prescribed most frequently, but phytotherapy surprisingly accounted for 27% of all monotherapies and 54% of all combination therapies. General practitioners and urologists (92% and 3.7% of overall prescribers, respectively) exhibited a similar prescription profile. Treatment initiation was medical in 95.4% of cases, consisting primarily of mono- therapy using alpha(1)-blockers (60.3%), phytotherapy (31.8%), or 5-ARIs (7.9%). Treatment was modified at extremely high rates within 12 mo of initiation (8.7%, 14.6%, and 12.9%, respectively). The median hospital stay for surgical management was far higher than in clinical trials. Long-term surgical complications and reoperation rates favored open prostatectomy. Incidence of pharmacologic treatment after surgery was as high as 13.8% at 12 mo.
Conclusions: This unique dynamic evaluation of clinical practice revealed unexpected results that contrast with previously published evidence from clinical trials. This approach may merit monitored and targeted measures to improve the level of care in the field. (C) 2013 European Association of Urology. Published by Elsevier B. V. All rights reserved.
C1 [Lukacs, Bertrand; Cornu, Jean-Nicolas; Haab, Francois; Cussenot, Olivier] Univ Paris 06, Tenon Hosp, AP HP, Dept Urol, Paris, France.
[Cornu, Jean-Nicolas] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Aout, Mounir; Tessier, Natacha; Vicaut, Eric] Univ Paris 07, Lariboisiere Fernand Widal Hosp, AP HP, Clin Res Unit, Paris, France.
[Hodee, Christophe] AP HP, Dept Informat, Paris, France.
[Merliere, Yvon] Ctr Rech Etud & Observat Condit Vie CREDOC, Paris, France.
[Merliere, Yvon; Moysan, Veronique] CNAMTS, Paris, France.
[Moysan, Veronique] CNAMTS, Bordeaux, France.
RP Lukacs, B (reprint author), Tenon Hosp, Dept Urol, 4 Rue Chine, F-75020 Paris, France.
EM bertrand.lukacs@tnn.aphp.fr; jncornu@hotmail.fr
FU Clinical Research Unit, Lariboisiere Fernand Widal Hospital, Assistance
Publique - Hopitaux de Paris, University Denis Diderot, Paris, France;
Association Nationale des Malades du Cancer de la Prostate
FX This study was financed by the Clinical Research Unit, Lariboisiere
Fernand Widal Hospital, Assistance Publique - Hopitaux de Paris,
University Denis Diderot, Paris, France. A grant was received from the
Association Nationale des Malades du Cancer de la Prostate. This
academic study was designed, conducted, analyzed, and written completely
independently of any sponsor. The Association Nationale des Malades du
Cancer de la Prostate did not participate in the design or conduct of
the study; the collection, analysis, and interpretation of the data; or
the preparation, review, or approval of the manuscript.
NR 35
TC 21
Z9 21
U1 0
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0302-2838
J9 EUR UROL
JI Eur. Urol.
PD SEP
PY 2013
VL 64
IS 3
BP 493
EP 501
DI 10.1016/j.eururo.2013.02.026
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 211VF
UT WOS:000323938700037
PM 23465519
ER
PT J
AU Shallom, SJ
Gardina, PJ
Myers, TG
Sebastian, Y
Conville, P
Calhoun, LB
Tettelin, H
Olivier, KN
Uzel, G
Sampaio, EP
Holland, SM
Zelazny, AM
AF Shallom, Shamira J.
Gardina, Paul J.
Myers, Timothy G.
Sebastian, Yinong
Conville, Patricia
Calhoun, Leslie B.
Tettelin, Herve
Olivier, Kenneth N.
Uzel, Gulbu
Sampaio, Elizabeth P.
Holland, Steven M.
Zelazny, Adrian M.
TI New Rapid Scheme for Distinguishing the Subspecies of the Mycobacterium
abscessus Group and Identifying Mycobacterium massiliense Isolates with
Inducible Clarithromycin Resistance
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID DESORPTION IONIZATION-TIME; FLIGHT MASS-SPECTROMETRY; GROWING
MYCOBACTERIA; TAXONOMIC STATUS; CYSTIC-FIBROSIS; CULTURE-MEDIA;
IDENTIFICATION; CHELONAE; BOLLETII; OUTBREAK
AB Mycobacterium abscessus (M. abscessus sensu lato, or the M. abscessus group) comprises three closely related taxa whose taxonomic statuses are under revision, i.e., M. abscessus sensu stricto, Mycobacterium bolletii, and Mycobacterium massiliense. We describe here a simple, robust, and cost-effective PCR-based method for distinguishing among M. abscessus, M. massiliense, and M. bolletii. Based on the M. abscessus ATCC 19977(T) genome, regions that discriminated between M. abscessus and M. massiliense were identified through array-based comparative genomic hybridization. A typing scheme using PCR primers designed for four of these locations was applied to 46 well-characterized clinical isolates comprising 29 M. abscessus, 15 M. massiliense, and 2 M. bolletii isolates previously identified by multitarget sequencing. Interestingly, 2 isolates unequivocally identified as M. massiliense were shown to have a full-length erm(41) gene instead of the expected gene deletion and showed inducible clarithromycin resistance after 14 days. We propose using this PCR-based typing scheme combined with erm(41) PCR for straightforward identification of M. abscessus, M. massiliense, and M. bolletii and the assessment of inducible clarithromycin resistance. This method can be easily integrated into a routine workflow to provide subspecies-level identification within 24 h after isolation of the M. abscessus group.
C1 [Shallom, Shamira J.; Conville, Patricia; Calhoun, Leslie B.; Zelazny, Adrian M.] NIH, Microbiol Serv, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Gardina, Paul J.; Myers, Timothy G.; Sebastian, Yinong] NIAID, Genom Technol Sect, Res Technol Branch, Div Intramural Res,NIH, Bethesda, MD 20892 USA.
[Tettelin, Herve] Univ Maryland, Sch Med, Inst Genome Sci, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
[Olivier, Kenneth N.; Uzel, Gulbu; Sampaio, Elizabeth P.; Holland, Steven M.; Zelazny, Adrian M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Sampaio, Elizabeth P.] Inst Oswaldo Cruz, Leprosy Lab, BR-20001 Rio De Janeiro, Brazil.
RP Zelazny, AM (reprint author), NIH, Microbiol Serv, Dept Lab Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM azelazny@mail.nih.gov
FU NIH; NIH Clinical Center; National Institute of Allergy and Infectious
Diseases; National Institute of Allergy and Infectious Diseases,
National Institutes of Health [HHSN272200900007C]
FX The Intramural Research Program of the NIH, the NIH Clinical Center, and
the National Institute of Allergy and Infectious Diseases supported this
research. H.T. was supported in part with federal funds from the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health (contract HHSN272200900007C).
NR 30
TC 32
Z9 32
U1 0
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD SEP
PY 2013
VL 51
IS 9
BP 2943
EP 2949
DI 10.1128/JCM.01132-13
PG 7
WC Microbiology
SC Microbiology
GA 202KL
UT WOS:000323214200022
PM 23804391
ER
PT J
AU Balaban, RS
AF Balaban, Robert S.
TI Evaluation of scientific productivity and excellence in the NHLBI
Division of Intramural Research
SO JOURNAL OF GENERAL PHYSIOLOGY
LA English
DT Editorial Material
C1 NHLBI, Bethesda, MD 20824 USA.
RP Balaban, RS (reprint author), NHLBI, Bethesda, MD 20824 USA.
NR 1
TC 1
Z9 1
U1 0
U2 4
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1295
J9 J GEN PHYSIOL
JI J. Gen. Physiol.
PD SEP
PY 2013
VL 142
IS 3
BP 177
EP 178
DI 10.1085/jgp.201311076
PG 2
WC Physiology
SC Physiology
GA 207ZJ
UT WOS:000323643300002
PM 23980190
ER
PT J
AU Stern, MD
Rios, E
Maltsev, VA
AF Stern, Michael D.
Rios, Eduardo
Maltsev, Victor A.
TI Life and death of a cardiac calcium spark
SO JOURNAL OF GENERAL PHYSIOLOGY
LA English
DT Article
ID POLYMORPHIC VENTRICULAR-TACHYCARDIA; INDUCED CA2+ RELEASE; IN MOUSE
MODEL; RYANODINE RECEPTOR; SARCOPLASMIC-RETICULUM; LUMINAL CA2+;
SKELETAL-MUSCLE; MYOCYTES; TERMINATION; LEAK
AB Calcium sparks in cardiac myocytes are brief, localized calcium releases from the sarcoplasmic reticulum (SR) believed to be caused by locally regenerative calcium-induced calcium release (CICR) via couplons, clusters of ryanodine receptors (RyRs). How such regeneration is terminated is uncertain. We performed numerical simulations of an idealized stochastic model of spark production, assuming a RyR gating scheme with only two states (open and closed). Local depletion of calcium in the SR was inevitable during a spark, and this could terminate sparks by interrupting CICR, with or without assumed modulation of RyR gating by SR lumenal calcium. Spark termination by local SR depletion was not robust: under some conditions, sparks could be greatly and variably prolonged, terminating by stochastic attrition-a phenomenon we dub "spark metastability." Spark fluorescence rise time was not a good surrogate for the duration of calcium release. Using a highly simplified, deterministic model of the dynamics of a couplon, we show that spark metastability depends on the kinetic relationship of RyR gating and junctional SR refilling rates. The conditions for spark metastability resemble those produced by known mutations of RyR2 and CASQ2 that cause life-threatening triggered arrhythmias, and spark metastability may be mitigated by altering the kinetics of the RyR in a manner similar to the effects of drugs known to prevent those arrhythmias. The model was unable to explain the distributions of spark amplitudes and rise times seen in chemically skinned cat atrial myocytes, suggesting that such sparks may be more complex events involving heterogeneity of couplons or local propagation among sub-clusters of RyRs.
C1 [Stern, Michael D.; Maltsev, Victor A.] NIA, Lab Cardiovasc Sci, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Rios, Eduardo] Rush Univ, Dept Mol Biophys & Physiol, Chicago, IL 60612 USA.
RP Stern, MD (reprint author), NIA, Lab Cardiovasc Sci, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM SternMi@mail.nih.gov
FU Intramural Research Program of the National Institute on Aging, National
Institutes of Health (NIH)
FX This work was supported by the Intramural Research Program of the
National Institute on Aging, National Institutes of Health (NIH).
NR 46
TC 23
Z9 23
U1 1
U2 11
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1295
J9 J GEN PHYSIOL
JI J. Gen. Physiol.
PD SEP
PY 2013
VL 142
IS 3
BP 257
EP 274
DI 10.1085/jgp.201311034
PG 18
WC Physiology
SC Physiology
GA 207ZJ
UT WOS:000323643300009
PM 23980195
ER
PT J
AU Stampalija, T
Chaiworapongsa, T
Romero, R
Chaemsaithong, P
Korzeniewski, SJ
Schwartz, AG
Ferrazzi, EM
Dong, Z
Hassan, SS
AF Stampalija, Tamara
Chaiworapongsa, Tinnakorn
Romero, Roberto
Chaemsaithong, Piya
Korzeniewski, Steven J.
Schwartz, Alyse G.
Ferrazzi, Enrico M.
Dong, Zhong
Hassan, Sonia S.
TI Maternal plasma concentrations of sST2 and angiogenic/anti-angiogenic
factors in preeclampsia
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE Biomarker; interleukin-33; pregnancy; sflt-1; Th2 immune response;
VEGFR-1
ID LATE-ONSET PREECLAMPSIA; UTERINE ARTERY DOPPLER; FOR-GESTATIONAL-AGE;
INTRAUTERINE GROWTH RESTRICTION; FACTOR RECEPTOR-1 CONCENTRATION;
PREGNANCY-INDUCED HYPERTENSION; ENDOTHELIAL-CELL DYSFUNCTION; LINKING
PLACENTAL ISCHEMIA; ATRIAL-NATRIURETIC-PEPTIDE; TYPE-2 CYTOKINE
PRODUCTION
AB Objectives: Angiogenic/anti-angiogenic factors have emerged as one of the promising biomarkers for the prediction of preeclampsia. Since not all patients with preeclampsia can be identified by these analytes, the search for additional biomarkers continues. The soluble form of ST2 (sST2), a protein capable of binding to interleukin (IL)-33 and thus contributing to a Th1-biased immune response, has been reported to be elevated in maternal plasma of women with preeclampsia. The aims of this study were to examine: (1) differences in maternal plasma concentrations of sST2 and IL-33 between women diagnosed with preeclampsia and those having uncomplicated pregnancies; (2) the relationship between sST2, umbilical and uterine artery Doppler velocimetry, and the severity of preeclampsia; and (3) the performance of sST2 and angiogenic/anti-angiogenic factors in identifying patients with preeclampsia at the time of diagnosis.
Methods: This cross-sectional study included women with preeclampsia (n = 106) and women with an uncomplicated pregnancy (n = 131). Plasma concentrations of sST2, IL-33, soluble vascular endothelial growth factor receptor (sVEGFR)-1, soluble endoglin (sEng) and placental growth factor (PlGF) were determined by enzyme linked immune sorbent assay. Area under the receiver operating characteristic curve (AUC) for the identification of preeclampsia was examined for each analyte.
Results: (1) Patients with preeclampsia had a higher mean plasma concentrations of sST2 than those with an uncomplicated pregnancy (p < 0.0001), while no significant difference in the mean plasma concentration of IL-33 between the two groups was observed; (2) the magnitude of this difference was greater in early-onset, compared to late-onset disease, and in severe compared to mild preeclampsia; (3) sST2 plasma concentrations did not correlate with the results of uterine or umbilical artery Doppler velocimetry (p = 0.7 and p = 1, respectively) among women with preeclampsia; (4) sST2 correlated positively with plasma concentrations of sVEGFR1-1 and sEng (Spearman's Rho = 0.72 and 0.63; each p < 0.0001), and negatively with PlGF (Spearman's Rho = -0.56, p < 0.0001); and (5) while the AUC achieved by sST2 and angiogenic/anti-angiogenic factors in identifying women with preeclampsia at the time of diagnosis were non-significantly different prior to term (<37 weeks of gestation), thereafter the AUC achieved by sST2 was significantly less than that achieved by angiogenic/anti-angiogenic factors.
Conclusions: Preeclampsia is associated with increased maternal plasma concentrations of sST2. The findings that sST2 concentrations do not correlate with uterine or umbilical artery Doppler velocimetry in women with preeclampsia suggest that elevated maternal plasma sST2 concentrations in preeclampsia are not related to the increased impedance to flow in the utero-placental circulation. The performance of sST2 in identifying preeclampsia at the time of diagnosis prior to 37 weeks of gestation was comparable to that of angiogenic/anti-angiogenic factors. It remains to be elucidated if an elevation of maternal plasma sST2 concentrations in pregnancy is specific to preeclampsia.
C1 [Stampalija, Tamara; Chaiworapongsa, Tinnakorn; Romero, Roberto; Chaemsaithong, Piya; Korzeniewski, Steven J.; Schwartz, Alyse G.; Dong, Zhong; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Stampalija, Tamara; Chaiworapongsa, Tinnakorn; Chaemsaithong, Piya; Korzeniewski, Steven J.; Schwartz, Alyse G.; Hassan, Sonia S.] Wayne State Univ, Detroit Med Ctr, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Stampalija, Tamara; Ferrazzi, Enrico M.] Univ Milan, Childrens Hosp Buzzi, Dept Obstet Gynecol, Milan, Italy.
RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM romeror@mail.nih.gov
RI Stampalija, Tamara/K-4900-2014
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Department of Health and
Human Services (NICHD/NIH); NICHD, NIH [HSN275201300006C]
FX This research was supported, in part, by the Perinatology Research
Branch, Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health, Department of Health and Human Services (NICHD/NIH); and, in
part, with Federal funds from NICHD, NIH under Contract No.
HSN275201300006C.
NR 177
TC 15
Z9 15
U1 0
U2 10
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1476-7058
EI 1476-4954
J9 J MATERN-FETAL NEO M
JI J. Matern.-Fetal Neonatal Med.
PD SEP
PY 2013
VL 26
IS 14
BP 1359
EP 1370
DI 10.3109/14767058.2013.784256
PG 12
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 203ZI
UT WOS:000323333300001
PM 23488689
ER
PT J
AU Stampalija, T
Romero, R
Korzeniewski, SJ
Chaemsaithong, P
Miranda, J
Yeo, L
Dong, Z
Hassan, SS
Chaiworapongsa, T
AF Stampalija, Tamara
Romero, Roberto
Korzeniewski, Steven J.
Chaemsaithong, Piya
Miranda, Jezid
Yeo, Lami
Dong, Zhong
Hassan, Sonia S.
Chaiworapongsa, Tinnakorn
TI Soluble ST2 in the fetal inflammatory response syndrome: in vivo
evidence of activation of the anti-inflammatory limb of the immune
response
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE Funisitis; IL-10; inflammation; intra-amniotic infection/inflammation;
preterm labor
ID PRETERM PREMATURE RUPTURE; TUMOR-NECROSIS-FACTOR; AMNIOTIC-FLUID
INFECTION; TOLL-LIKE RECEPTORS; BLOOD-CELL COUNT; T-HELPER-CELL;
INHIBITS CYTOKINE PRODUCTION; POLYMERASE-CHAIN-REACTION; HERPES-SIMPLEX
INFECTION; CENTRAL-NERVOUS-SYSTEM
AB Objective: Inflammation is a mechanism of host response to infection, which can be harmful when inappropriately modulated. Soluble ST2 (sST2) is a decoy receptor of interleukin (IL)-33, and this complex modulates the balance in the Th1/Th2 immune response. Moreover, sST2 inhibits the production of pro-inflammatory cytokines in cooperation with an anti-inflammatory cytokine, IL-10. The objectives of this study were to: (1) determine whether umbilical cord plasma sST2 concentration differs between preterm neonates with and without funisitis and between those with and without the fetal inflammatory response syndrome (FIRS); and (2) evaluate the relationship between sST2 and IL-10 among neonates with funisitis and/or FIRS.
Methods: Umbilical cord plasma was collected from neonates delivered prematurely due to preterm labor or preterm prelabor rupture of membranes with (n = 36), and without funisitis (n = 30). FIRS (umbilical cord IL-6 concentration >= 17.5 pg/mL) was identified in 29 neonates. Plasma sST2 and IL-10 concentrations were determined by enzyme linked immune sorbent assay.
Results: The median umbilical cord plasma sST2 concentration was 6.7-fold higher in neonates with FIRS than in those without FIRS (median 44.6 ng/mL, interquartile range (IQR) 13.8-80.3 ng/mL versus median 6.7 ng/mL, IQR 5.6-20.1 ng/mL; p < 0.0001). Similarly, the median umbilical cord plasma sST2 concentration was 2.7-fold higher in neonates with funisitis than in those without funisitis (median 19.1 ng/mL; IQR 7.1-75.0 ng/mL versus median 7.2 ng/mL; IQR 5.9-23.1 ng/mL; p = 0.008). There was a strong positive correlation between sST2 and IL-10 in neonates with funisitis and/or FIRS (Spearman's Rho = 0.7, p < 0.0001).
Conclusion: FIRS and funisitis are associated with an elevation of umbilical cord plasma concentrations of soluble ST2. This protein represents an important mediator of the immune response in neonates diagnosed with FIRS by promoting an anti-inflammatory effect in association with IL-10.
C1 [Stampalija, Tamara; Romero, Roberto; Korzeniewski, Steven J.; Chaemsaithong, Piya; Miranda, Jezid; Yeo, Lami; Dong, Zhong; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Stampalija, Tamara; Romero, Roberto; Korzeniewski, Steven J.; Chaemsaithong, Piya; Miranda, Jezid; Yeo, Lami; Dong, Zhong; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Stampalija, Tamara; Korzeniewski, Steven J.; Chaemsaithong, Piya; Miranda, Jezid; Yeo, Lami; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn] Wayne State Univ, Dept Obstet Gynecol, Detroit, MI 48201 USA.
[Stampalija, Tamara] Univ Milan, Dept Biol & Clin Sci, Milan, Italy.
RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM romeror@mail.nih.gov
RI Stampalija, Tamara/K-4900-2014
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Department of Health and
Human Services [HHSN275201300006C]
FX This project has been funded in whole or in part with Federal funds from
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Department of Health and
Human Services, under Contract No. HHSN275201300006C.
NR 202
TC 9
Z9 9
U1 0
U2 6
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 SEP
PY 2013
VL 26
IS 14
BP 1384
EP 1393
DI 10.3109/14767058.2013.784258
PG 10
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 203ZI
UT WOS:000323333300004
PM 23488731
ER
PT J
AU Floreani, A
Caroli, D
Lazzari, R
Memmo, A
Vidali, E
Colavito, D
D'Arrigo, A
Leon, A
Romero, R
Gervasi, MT
AF Floreani, Annarosa
Caroli, Diego
Lazzari, Roberta
Memmo, Alessia
Vidali, Elisa
Colavito, Davide
D'Arrigo, Antonello
Leon, Alberta
Romero, Roberto
Gervasi, Maria Teresa
TI Intrahepatic cholestasis of pregnancy: new insights into its
pathogenesis
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE Genetics; intrahepatic cholestsis of pregnancy; microarray
ID PHOSPHOLIPID TRANSFER PROTEIN; MDR3 GENE; MUTATION; PRURITUS;
GABAPENTIN; TRANSPORT; VARIANTS; PROFILES; WOMEN; BURNS
AB Aim: To search a specific gene expression profile in women with intrahepatic cholestasis of pregnancy (ICP) and to evaluate the maternal and foetal outcome.
Methods: We consecutively enrolled 12 women with ICP and 12 healthy pregnant controls. The gene expression profile was assayed with the microarray technique including a panel of 5541 human genes. Microarray data were validated by real-time PCR technique.
Results: Caesarean delivery was performed in eight patients with ICP versus three controls (p = 0.05). ICP women delivered at earlier gestational age than control (p < 0.001). Foetal distress was recorded in two babies, but we failed to find any correlation between bile salt concentration and foetal distress. Twenty genes potentially correlated with ICP were found differentially expressed (p < 0.05). Among these, three belong to genetic classes involved in pathogenic mechanisms of ICP: (1) pathophysiology of pruritus (GABRA2, cases versus controls = 2, upregulated gene); (2) lipid metabolism and bile composition (HLPT, cases versus controls = 0.6, down-regulated gene) and (3) protein trafficking and cytoskeleton arrangement (KIFC3, cases versus controls = 0.5, down-regulated gene).
Conclusions: Different gene expression may contribute to the complex pathogenesis of ICP. An upregulation of GABRA2 receptor may indicate that GABA may play a role in the pathogenesis of pruritus in this condition.
C1 [Floreani, Annarosa; Caroli, Diego; Lazzari, Roberta] Univ Padua, Dept Surg Oncol & Gastroenterol, Padua, Italy.
[Memmo, Alessia; Vidali, Elisa; Gervasi, Maria Teresa] Azienda Osped, Dept Obstet & Gynaecol, Padua, Italy.
[Colavito, Davide; D'Arrigo, Antonello; Leon, Alberta] Res & Innovat, Padua, Italy.
[Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Romero, Roberto] Wayne State Univ, Sch Med, Dept Obstet & Gynaecol, Detroit, MI USA.
RP Floreani, A (reprint author), Dept Surg & Gastroenterol Sci, Via Giustiniani 2, I-35128 Padua, Italy.
EM annarosa.floreani@unipd.it
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, NIH, DHHS
FX The authors report no conflict of interest. The research was supported,
in part, by the Perinatology Research Branch, Division of Intramural
Research, Eunice Kennedy Shriver National Institute of Child Health and
Human Development, NIH, DHHS and by a Ministerial grant (ex 60% fund).
NR 35
TC 10
Z9 12
U1 0
U2 4
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 SEP
PY 2013
VL 26
IS 14
BP 1410
EP 1415
DI 10.3109/14767058.2013.783810
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 203ZI
UT WOS:000323333300008
PM 23480690
ER
PT J
AU Brown, P
Gipson, C
AF Brown, Patricia
Gipson, Chester
TI A word from OLAW and USDA
SO LAB ANIMAL
LA English
DT Editorial Material
C1 [Brown, Patricia] NIH, HHS, OD, OLAW,OER, Bethesda, MD 20892 USA.
[Gipson, Chester] USDA, APHIS, AC, Washington, DC USA.
RP Brown, P (reprint author), NIH, HHS, OD, OLAW,OER, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0093-7355
J9 LAB ANIMAL
JI Lab Anim.
PD SEP
PY 2013
VL 42
IS 9
BP 318
EP 318
PG 1
WC Veterinary Sciences
SC Veterinary Sciences
GA 211AO
UT WOS:000323876700015
PM 23965560
ER
PT J
AU Hughes, L
AF Hughes, LaTesa
TI Training initiatives for non-native English speakers in Laboratory
animal care
SO LAB ANIMAL
LA English
DT Editorial Material
C1 NIH, Bethesda, MD 20892 USA.
RP Hughes, L (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0093-7355
J9 LAB ANIMAL
JI Lab Anim.
PD SEP
PY 2013
VL 42
IS 9
BP 335
EP 335
PG 1
WC Veterinary Sciences
SC Veterinary Sciences
GA 211AO
UT WOS:000323876700020
PM 23965567
ER
PT J
AU Key, TJ
Appleby, PN
Reeves, GK
Travis, RC
Alberg, AJ
Barricarte, A
Berrino, F
Krogh, V
Sieri, S
Brinton, LA
Dorgan, JF
Dossus, L
Dowsett, M
Eliassen, AH
Fortner, RT
Hankinson, SE
Helzlsouer, KJ
Hoffman-Bolton, J
Comstock, GW
Kaaks, R
Kahle, LL
Koenig, K
Zeleniuch-Jacquotte, A
Muti, P
Overvad, K
Peeters, PHM
Riboli, E
Rinaldi, S
Rollison, DE
Stanczyk, FZ
Trichopoulos, D
Tworoger, SS
Tworoger, SS
Vineis, P
AF Key, T. J.
Appleby, P. N.
Reeves, G. K.
Travis, R. C.
Alberg, A. J.
Barricarte, A.
Berrino, F.
Krogh, V.
Sieri, S.
Brinton, L. A.
Dorgan, J. F.
Dossus, L.
Dowsett, M.
Eliassen, A. H.
Fortner, R. T.
Hankinson, S. E.
Helzlsouer, K. J.
Hoffman-Bolton, J.
Comstock, George W.
Kaaks, R.
Kahle, L. L.
Koenig, K.
Zeleniuch-Jacquotte, A.
Muti, P.
Overvad, K.
Peeters, P. H. M.
Riboli, E.
Rinaldi, S.
Rollison, D. E.
Stanczyk, F. Z.
Trichopoulos, D.
Tworoger, S. S.
Tworoger, S. S.
Vineis, P.
TI Sex hormones and risk of breast cancer in premenopausal women: a
collaborative reanalysis of individual participant data from seven
prospective studies
SO LANCET ONCOLOGY
LA English
DT Article
ID GROWTH-FACTOR LEVELS; POSTMENOPAUSAL WOMEN; ENDOGENOUS HORMONES; SERUM
ANDROGENS; TESTOSTERONE; NUTRITION; ESTRADIOL; ESTROGENS; ETIOLOGY;
DISEASE
AB Background Associations between circulating concentrations of oestrogens, progesterone, and androgens with breast cancer and related risk factors in premenopausal women are not well understood. We aimed to characterise these associations with a pooled analysis of data from seven studies.
Methods Individual participant data for prediagnostic sex hormone and sex hormone-binding globulin (SHBG) concentrations were contributed from seven prospective studies. We restricted analyses to women who were premenopausal and younger than 50 years at blood collection, and to women with breast cancer diagnosed before age 50 years. We estimated odds ratios (ORs) with 95% CIs for breast cancer associated with hormone concentrations by conditional logistic regression in cases and controls matched for age, date of blood collection, and day of cycle, with stratification by study and further adjustment for cycle phase. We examined associations of hormones with risk factors for breast cancer in control women by comparing geometric mean hormone concentrations in categories of these risk factors, adjusted for study, age, phase of menstrual cycle, and body-mass index (BMI). All statistical tests were two-sided.
Findings We included data for up to 767 women with breast cancer and 1699 controls in the risk analyses. Breast cancer risk was associated with a doubling in concentrations of oestradiol (OR 1.19, 95% CI 1.06-1.35), calculated free oestradiol (1.17, 1.03-1.33), oestrone (1.27, 1.05-1.54), androstenedione (1.30, 1.10-1.55), dehydroepiandrosterone sulphate (1.17, 1.04-1.32), testosterone (1.18, 1.03-1.35), and calculated free testosterone (1.08, 0.97-1.21). Breast cancer risk was not associated with luteal phase progesterone (doubling in concentration OR 1.00, 95% CI 0.92-1.09), and adjustment for other factors had little effect on any of these ORs. Cross-sectional analyses in control women showed several associations of sex hormones with breast cancer risk factors.
Interpretation Circulating oestrogens and androgens are positively associated with the risk for breast cancer in premenopausal women.
C1 [Key, T. J.; Appleby, P. N.; Reeves, G. K.; Travis, R. C.] Univ Oxford, Canc Epidemiol Unit, Nuffi eld Dept Populat Hlth, Oxford, England.
[Alberg, A. J.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Alberg, A. J.] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA.
[Barricarte, A.] Navarre Publ Hlth Inst, Pamplona, Spain.
[Berrino, F.; Krogh, V.; Sieri, S.] Fondazione IRCCS Ist Nazl Tumori, Milan, Italy.
[Brinton, L. A.] Natl Canc Inst, Bethesda, MD USA.
[Dorgan, J. F.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Dossus, L.] INSERM, Ctr Res Epidemiol & Populat Hlth, CESP, Nutr Hormones & Womens Hlth Team, Villejuif, France.
[Dowsett, M.] Inst Canc Res, London SW3 6JB, England.
[Eliassen, A. H.] Harvard Univ, Sch Med, Channing Div Network Med, Dept Med, Boston, MA USA.
[Eliassen, A. H.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Eliassen, A. H.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Fortner, R. T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med,Dept Med, Boston, MA 02115 USA.
[Fortner, R. T.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Hankinson, S. E.] Harvard Univ, Sch Med, Boston, MA USA.
[Hankinson, S. E.] Brigham & Womens Hosp, Channing Div Network Med, Dept Med, Boston, MA 02115 USA.
[Hankinson, S. E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Trichopoulos, D.] Acad Athens, Bur Epidemiol Res, Athens, Greece.
[Trichopoulos, D.] Hellen Hlth Fdn, Athens, Greece.
[Tworoger, S. S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med,Dept Med, Boston, MA 02115 USA.
[Tworoger, S. S.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Vineis, P.] HuGeF Fdn, Turin, Italy.
[Vineis, P.] Imperial Coll, London, England.
RP Key, TJ (reprint author), Univ Oxford, Nuffield Dept Populat Hlth, Endogenous Hormones & Breast Canc Collaborat Grp, Canc Epidemiol Unit, Richard Doll Bldg, Oxford OX3 7LF, England.
EM tim.key@ceu.ox.ac.uk
RI Brinton, Louise/G-7486-2015; Krogh, Vittorio/K-2628-2016; Sieri,
Sabina/K-4667-2016;
OI Brinton, Louise/0000-0003-3853-8562; Krogh,
Vittorio/0000-0003-0122-8624; Sieri, Sabina/0000-0001-5201-172X;
Fortner, Renee/0000-0002-1426-8505
FU Cancer Research UK
FX Funding Cancer Research UK.
NR 39
TC 49
Z9 49
U1 0
U2 12
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
J9 LANCET ONCOL
JI Lancet Oncol.
PD SEP
PY 2013
VL 14
IS 10
BP 1009
EP 1019
DI 10.1016/S1470-2045(13)70301-2
PG 11
WC Oncology
SC Oncology
GA 211WM
UT WOS:000323942500047
ER
PT J
AU Griebel, G
Holmes, A
AF Griebel, Guy
Holmes, Andrew
TI 50 years of hurdles and hope in anxiolytic drug discovery
SO NATURE REVIEWS DRUG DISCOVERY
LA English
DT Review
ID ANXIETY-LIKE BEHAVIOR; CORTICOTROPIN-RELEASING-FACTOR;
NATIONAL-COMORBIDITY-SURVEY; GLUTAMIC-ACID DECARBOXYLASE; SEROTONIN
5-HT1A RECEPTOR; CB1 CANNABINOID RECEPTORS; ELEVATED PLUS-MAZE; DSM-IV
DISORDERS; NULL MUTANT MICE; FEAR-POTENTIATED STARTLE
AB Anxiety disorders are the most prevalent group of psychiatric diseases, and have high personal and societal costs. The search for novel pharmacological treatments for these conditions is driven by the growing medical need to improve on the effectiveness and the side effect profile of existing drugs. A huge volume of data has been generated by anxiolytic drug discovery studies, which has led to the progression of numerous new molecules into clinical trials. However, the clinical outcome of these efforts has been disappointing, as promising results with novel agents in rodent studies have very rarely translated into effectiveness in humans. Here, we analyse the major trends from preclinical studies over the past 50 years conducted in the search for new drugs beyond those that target the prototypical anxiety-associated GABA (gamma-aminobutyric acid)-benzodiazepine system, which have focused most intensively on the serotonin, neuropeptide, glutamate and endocannabinoid systems. We highlight various key issues that may have hampered progress in the field, and offer recommendations for how anxiolytic drug discovery can be more effective in the future.
C1 [Griebel, Guy] Sanofi, Exploratory Unit, F-91385 Chilly Mazarin, France.
[Holmes, Andrew] US Natl Inst Alcohol Abuse & Alcoholism, Lab Behav & Genom Neurosci, US Natl Inst Hlth, Rockville, MD 20852 USA.
RP Griebel, G (reprint author), Sanofi, Exploratory Unit, F-91385 Chilly Mazarin, France.
EM Guy.Griebel@sanofi.com
RI Griebel, Guy/F-8752-2014
OI Griebel, Guy/0000-0002-6052-9438
FU Intramural NIH HHS [ZIA AA000411-10]
NR 286
TC 84
Z9 88
U1 8
U2 46
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1776
EI 1474-1784
J9 NAT REV DRUG DISCOV
JI Nat. Rev. Drug Discov.
PD SEP
PY 2013
VL 12
IS 9
BP 667
EP 687
DI 10.1038/nrd4075
PG 21
WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy
SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy
GA 211EF
UT WOS:000323887000018
PM 23989795
ER
PT J
AU Eisenberg, DP
Kleinman, J
Berman, KF
AF Eisenberg, Daniel Paul
Kleinman, Joel
Berman, Karen F.
TI Commentary on "Synergistic Effects of COMT and TPH2 on Social Cognition"
Epistasis and Complex Neuropsychiatric Phenotypes
SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES
LA English
DT Editorial Material
C1 [Eisenberg, Daniel Paul; Berman, Karen F.] NIMH, Sect Integrat Neuroimaging, NIH, Intramural Res Program,DHHS, Bethesda, MD 20892 USA.
[Kleinman, Joel] NIMH, Neuropathol Sect, NIH, Intramural Res Program,DHHS, Bethesda, MD 20892 USA.
RP Eisenberg, DP (reprint author), NIMH, Sect Integrat Neuroimaging, NIH, 9000 Rockville Pike,Bldg 10,Room 3C209, Bethesda, MD 20892 USA.
EM eisenbergd@mail.nih.gov
RI Eisenberg, Daniel/C-7432-2014; Eisenberg, Daniel/S-4342-2016
FU Intramural NIH HHS [Z01 MH002717-13]
NR 5
TC 0
Z9 0
U1 0
U2 1
PU GUILFORD PUBLICATIONS INC
PI NEW YORK
PA 72 SPRING STREET, NEW YORK, NY 10012 USA
SN 0033-2747
J9 PSYCHIATRY
JI Psychiatry-Interpers. Biol. Process.
PD FAL
PY 2013
VL 76
IS 3
BP 295
EP 297
PG 3
WC Psychiatry
SC Psychiatry
GA 210TD
UT WOS:000323856600008
PM 23965266
ER
PT J
AU Kozmin, SG
Schaaper, RM
AF Kozmin, Stanislav G.
Schaaper, Roel M.
TI Genetic characterization of moaB mutants of Escherichia coli
SO RESEARCH IN MICROBIOLOGY
LA English
DT Article
DE Molybdenum cofactor; moaABCDE operon; mogA gene;
6-N-Hydroxylaminopurine; Chlorate resistance
ID MOLYBDENUM-COFACTOR BIOSYNTHESIS; HYDROXYLATED BASE ANALOGS; RESISTANCE;
K-12; COLLECTION; REDUCTASE; STRAINS
AB The moaABCDE operon of Escherichia coli encodes enzymes essential for the biosynthesis of the molybdenum cofactor (Moco). However, the role of the moaB gene within this operon has remained enigmatic. Here, we have investigated the effect of moaB defects on two phenotypes diagnostic for Moco-deficiency: chlorate-resistance and sensitivity to the base analog 6-N-hydroxylaminopurine (HAP). We found that transposon insertions in moaB caused partial Moco-deficiency associated with chlorate-resistance, but not for HAP-sensitivity. On the other hand, in-frame deletions of moaB, or moaB overexpression, had no effect on either phenotype. Our combined data are consistent with the lack of any role for MoaB in Moco biosynthesis in E. coli. Published by Elsevier Masson SAS on behalf of Institut Pasteur.
C1 [Kozmin, Stanislav G.; Schaaper, Roel M.] NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA.
RP Schaaper, RM (reprint author), NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA.
EM stanislav.kozmin@duke.edu; schaaper@niehs.nih.gov
RI Kozmin, Stanislav/J-6849-2012
OI Kozmin, Stanislav/0000-0002-4128-4447
FU National Institute of Environmental Health Sciences (NIEHS) [ES050170]
FX We thank Drs. K. Chan and M. Itsko of the NIEHS for their helpful
comments on the manuscript for this paper. This work was supported by
project ES050170 of the Intramural Research Program of the National
Institute of Environmental Health Sciences (NIEHS).
NR 21
TC 0
Z9 0
U1 1
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0923-2508
J9 RES MICROBIOL
JI Res. Microbiol.
PD SEP
PY 2013
VL 164
IS 7
BP 689
EP 694
DI 10.1016/j.resmic.2013.05.001
PG 6
WC Microbiology
SC Microbiology
GA 212VL
UT WOS:000324010800001
PM 23680484
ER
PT J
AU Szabo, S
Xu, Y
Romero, R
Fule, T
Karaszi, K
Bhatti, G
Varkonyi, T
Varkonyi, I
Krenacs, T
Dong, Z
Tarca, AL
Chaiworapongsa, T
Hassan, SS
Papp, Z
Kovalszky, I
Than, NG
AF Szabo, Szilvia
Xu, Yi
Romero, Roberto
Fule, Tibor
Karaszi, Katalin
Bhatti, Gaurav
Varkonyi, Tibor
Varkonyi, Ildiko
Krenacs, Tibor
Dong, Zhong
Tarca, Adi L.
Chaiworapongsa, Tinnakorn
Hassan, Sonia S.
Papp, Zoltan
Kovalszky, Ilona
Than, Nandor Gabor
TI Changes of placental syndecan-1 expression in preeclampsia and HELLP
syndrome
SO VIRCHOWS ARCHIV
LA English
DT Article
DE Cell signaling; Pregnancy; Proteoglycan; Syncytiotrophoblast; Systemic
inflammation; Virtual microscopy
ID INTRAUTERINE GROWTH RESTRICTION; ELEVATED LIVER-ENZYMES;
FOR-GESTATIONAL-AGE; CELL-SURFACE; SERUM CONCENTRATIONS;
HEPARAN-SULFATE; PREGNANCY; PROTEOGLYCANS; TRANSMEMBRANE; MICROARRAY
AB Preeclampsia is characterized by maternal systemic anti-angiogenic and pro-inflammatory states. Syndecan-1 is a cell surface proteoglycan expressed by the syncytiotrophoblast, which plays an important role in angiogenesis and resolution of inflammation. Our aim was to examine placental syndecan-1 expression in preeclampsia with or without hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. Placentas were obtained from women in the following groups: (1) late-onset preeclampsia (n=8); (2) early-onset preeclampsia without (n=7) and (3) with HELLP syndrome (n=8); (4) preterm controls (n=5); and (5) term controls (n=9). Tissue microarrays (TMAs) were constructed from paraffin-embedded placentas. TMA slides were immunostained for syndecan-1 and evaluated using microscopy, virtual microscopy, and semi-automated image analysis. Maternal sera from patients with preeclampsia (n=49) and controls (n=32) were immunoassayed for syndecan-1. BeWo cells were treated with Forskolin or Latrunculin B or kept in ischemic conditions. SDC1 expression and syndecan-1 production were investigated with qRT-PCR, confocal microscopy, and immunoassays. Syndecan-1 was localized to the syncytiotrophoblast apical membrane in normal placentas. Syndecan-1 immunoscores were higher in late-onset preeclampsia (p=0.0001) and early-onset preeclampsia with or without HELLP syndrome (p=0.02 for both) than in controls. Maternal serum syndecan-1 concentration was lower in preeclampsia (median, 673 ng/ml; interquartile range, 459-1,161 ng/ml) than in controls (1,158 ng/ml; 622-1,480 ng/ml). SDC1 expression and syndecan-1 immunostainings in BeWo cells and syndecan-1 concentrations in supernatants increased during cell differentiation. Disruption of the actin cytoskeleton with Latrunculin B decreased syndecan-1 release, while ischemic conditions increased it. Syncytiotrophoblastic syndecan-1 expression depends on the differentiation of villous trophoblasts, and trophoblastic syndecan-1 release is decreased in preeclampsia and HELLP syndrome. This phenomenon may be related to the disturbed syncytiotrophoblastic cortical actin cytoskeleton and associated with maternal anti-angiogenic and pro-inflammatory states in these syndromes.
C1 [Szabo, Szilvia] Semmelweis Univ, Fac Hlth Sci, Dept Morphol & Physiol, H-1085 Budapest, Hungary.
[Xu, Yi; Romero, Roberto; Bhatti, Gaurav; Dong, Zhong; Tarca, Adi L.; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.; Than, Nandor Gabor] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, US Dept HHS, Bethesda, MD USA.
[Fule, Tibor; Karaszi, Katalin; Krenacs, Tibor; Kovalszky, Ilona] Semmelweis Univ, Fac Med, Dept Pathol & Expt Canc Res 1, H-1085 Budapest, Hungary.
[Varkonyi, Tibor; Papp, Zoltan; Than, Nandor Gabor] Semmelweis Univ, Fac Med, Dept Obstet & Gynecol 1, H-1085 Budapest, Hungary.
[Papp, Zoltan; Than, Nandor Gabor] Matern Private Clin Obstet, Budapest, Hungary.
[Varkonyi, Ildiko] Sundsvall Hosp, Dept Pathol & Cytol, Sundsvall, Sweden.
[Tarca, Adi L.] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA.
[Chaiworapongsa, Tinnakorn; Hassan, Sonia S.; Than, Nandor Gabor] Wayne State Univ, Dept Obstet & Gynecol, Sch Med, Detroit, MI 48201 USA.
RP Romero, R (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, US Dept HHS, Bethesda, MD USA.
EM romeror@mail.nih.gov; koval@korb1.sote.hu; gabor_than@yahoo.com
FU European Union FP6 [Pregenesys 037244]; Hungarian Scientific Research
Fund (OTKA) [67925]; Perinatology Research Branch, Division of
Intramural Research, Eunice Kennedy Shriver National Institute of Child
Health and Human Development, National Institutes of Health, U. S.
Department of Health and Human Services
FX The authors are grateful to Dr. Noemi Mihalik, Edit Parsch, Levente
Ficsor, and Gabor Kiszler (Budapest), and to Rona Wang, Yang Jiang,
Olesya Plazyo, Mary Olive, Sandy Field, Ted Price, and Gerardo Rodriguez
(Detroit) for their helpful technical assistance, and to Maureen McGerty
and Andrea Bernard (Wayne State University) for their critical readings
of the manuscript. Figure 6 was adapted from Riquelme et al. [59] with
kind permission from Springer Science and Business Media. This research
has been supported in part by the following grants: the European Union
FP6 Grant "Pregenesys 037244" (to N.G.T.), the Hungarian Scientific
Research Fund (OTKA) Grant 67925 (to N.G.T.), and the Perinatology
Research Branch, Division of Intramural Research, Eunice Kennedy Shriver
National Institute of Child Health and Human Development, National
Institutes of Health, U. S. Department of Health and Human Services.
NR 67
TC 6
Z9 7
U1 0
U2 11
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0945-6317
J9 VIRCHOWS ARCH
JI Virchows Arch.
PD SEP
PY 2013
VL 463
IS 3
BP 445
EP 458
DI 10.1007/s00428-013-1426-0
PG 14
WC Pathology
SC Pathology
GA 211KB
UT WOS:000323904700010
PM 23807541
ER
PT J
AU Garrison, AR
Radoshitzky, SR
Kota, KP
Pegoraro, G
Ruthel, G
Kuhn, JH
Altamura, LA
Kwilas, SA
Bavari, S
Haucke, V
Schmaljohn, CS
AF Garrison, Aura R.
Radoshitzky, Sheli R.
Kota, Krishna P.
Pegoraro, Gianluca
Ruthel, Gordon
Kuhn, Jens H.
Altamura, Louis A.
Kwilas, Steven A.
Bavari, Sina
Haucke, Volker
Schmaljohn, Connie S.
TI Crimean-Congo hemorrhagic fever virus utilizes a clathrin- and early
endosome-dependent entry pathway
SO VIROLOGY
LA English
DT Article
DE Bunyavirus; CCHF; Crimean-Congo hemorrhagic fever; Nairovirus; Virus
entry
ID RECEPTOR-MEDIATED ENDOCYTOSIS; CELL-FUSION; CONFORMATIONAL-CHANGES;
MAMMALIAN-CELLS; HOST-CELLS; GLYCOPROTEIN; PSEUDOVIRIONS; ACIDIFICATION;
REPLICATION; TRAFFICKING
AB The early events in Crimean-Congo hemorrhagic fever virus (CCHFV) have not been completely characterized. Earlier work indicated that CCHFV likely enters cells by clathrin-mediated endocytosis (CME). Here we provide confirmatory evidence for CME entry by showing that CCHFV infection is inhibited in cells treated with Pitstop 2, a drug that specifically and reversibly interferes with the dynamics of clathrin-coated pits. Additionally, we show that CCHFV infection is inhibited by siRNA depletion of the clathrin pit associated protein AP-2. Following CME entry, we show that CCHFV has a pH-dependent entry step, with virus inactivation occurring at pH 6.0 and below. To more precisely define the endosomal trafficking of CCHFV, we show for the first time that overexpression of the dominant negative forms of Rab5 protein but not Rab7 protein inhibits CCHFV infection. These results indicate that CCHFV likely enters cells through the early endosomal compalunent. Published by Elsevier Inc.
C1 [Garrison, Aura R.; Radoshitzky, Sheli R.; Kota, Krishna P.; Pegoraro, Gianluca; Ruthel, Gordon; Altamura, Louis A.; Kwilas, Steven A.; Bavari, Sina; Schmaljohn, Connie S.] US Army Med Res Inst Infect Dis, Ft Detrick, MD USA.
[Kuhn, Jens H.] NIAID, Integrated Res Facil Ft Detrick, NIH, Ft Detrick, MD USA.
[Haucke, Volker] Leibniz Inst Mol Pharmakol FMP, Berlin, Germany.
RP Schmaljohn, CS (reprint author), US Army Med Res Inst Infect Dis, 1425 Porter St, Ft Detrick, MD USA.
EM connie.schmaljohn@us.army.mil
RI Kuhn, Jens H./B-7615-2011;
OI Kuhn, Jens H./0000-0002-7800-6045; Pegoraro,
Gianluca/0000-0003-2843-9464; Haucke, Volker/0000-0003-3119-6993
FU Military Infectious Diseases Research Program; NIAID
[HHSN272200200016I]; German Funding Agency DFG [SFB765/B04]
FX This work was funded by the Military Infectious Diseases Research
Program. JHK performed this work as an employee of Tunnell Government
Services, a subcontractor to Battelle Memorial Institute under its prime
contract with NIAID, under Contract no. HHSN272200200016I. V.H.
gratefully acknowledges support by the German Funding Agency DFG
(SFB765/B04).
NR 60
TC 18
Z9 18
U1 0
U2 15
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD SEP
PY 2013
VL 444
IS 1-2
BP 45
EP 54
DI 10.1016/j.virol.2013.05.030
PG 10
WC Virology
SC Virology
GA 210ZJ
UT WOS:000323873600007
PM 23791227
ER
PT J
AU Vasilakis, N
Widen, S
Mayer, SV
Seymour, R
Wood, TG
Popov, V
Guzman, H
da Rosa, APAT
Ghedin, E
Holmes, EC
Walker, PJ
Tesh, RB
AF Vasilakis, Nikos
Widen, Steven
Mayer, Sandra V.
Seymour, Robert
Wood, Thomas G.
Popov, Vsevolov
Guzman, Hilda
da Rosa, Amelia P. A. Travassos
Ghedin, Elodie
Holmes, Edward C.
Walker, Peter J.
Tesh, Robert B.
TI Niakha virus: A novel member of the family Rhabdoviridae isolated from
phlebotomine sandflies in Senegal
SO VIROLOGY
LA English
DT Article
DE Niakha virus (NIAV); Rhabdoviridae; Phlebotomine sandflies; Complement
fixation; West Africa
ID VESICULAR STOMATITIS-VIRUS; GLYCOPROTEIN-G; ARBOVIRUSES; PHYLOGENIES;
ALIGNMENT; GENES; SMART; FORM
AB Members of the family Rhabdoviridae have been assigned to eight genera but many remain unassigned. Rhabdoviruses have a remarkably diverse host range that includes terrestrial and marine animals, invertebrates and plants. Transmission of some rhabdoviruses often requires an arthropod vector, such as mosquitoes, midges, sandflies, ticks, aphids and leafhoppers, in which they replicate. Herein we characterize Niakha virus (NIAV), a previously uncharacterized rhabdovirus isolated from phebotomine sandflies in Senegal. Analysis of the 11,124 nt genome sequence indicates that it encodes the five common rhabdovirus proteins with alternative ORFs in the M, G and L genes. Phylogenetic analysis of the L protein indicate that NIAV's closest relative is Oak Vale rhabdovirus, although in this analysis NIAV is still so phylogenetically distinct that it might be classified as distinct from the eight currently recognized Rhabdoviridae genera. This observation highlights the vast, and yet not fully recognized diversity, of this family. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Vasilakis, Nikos; Mayer, Sandra V.; Seymour, Robert; Popov, Vsevolov; Guzman, Hilda; da Rosa, Amelia P. A. Travassos; Tesh, Robert B.] Ctr Biodef & Emerging Infect Dis, Galveston, TX USA.
[Vasilakis, Nikos; Mayer, Sandra V.; Seymour, Robert; Popov, Vsevolov; Guzman, Hilda; da Rosa, Amelia P. A. Travassos; Tesh, Robert B.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA.
[Vasilakis, Nikos; Tesh, Robert B.] Univ Texas Med Branch, Ctr Trop Dis, Galveston, TX 77555 USA.
[Vasilakis, Nikos; Tesh, Robert B.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77555 USA.
[Widen, Steven; Wood, Thomas G.] Univ Texas Med Branch, Dept Biochem & Mol Biol, Galveston, TX 77555 USA.
[Ghedin, Elodie] Univ Pittsburgh, Dept Computat & Syst Biol, Ctr Vaccine Res, Pittsburgh, PA 15261 USA.
[Holmes, Edward C.] Univ Sydney, Sch Biol Sci, Sydney Emerging Infect & Biosecur Inst, Sydney, NSW 2006, Australia.
[Holmes, Edward C.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia.
[Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Walker, Peter J.] CSIRO Anim Food & Hlth Sci, Australian Anim Hlth Lab, Geelong, Vic 3220, Australia.
RP Vasilakis, N (reprint author), Univ Texas Med Branch, Ctr Biodef & Emerging Infect Dis, 2-138D Keiller Bldg,301 Univ Blvd, Galveston, TX 77555 USA.
EM nivasila@utmb.edu
RI Walker, Peter/H-6059-2013;
OI Walker, Peter/0000-0003-1851-642X; Holmes, Edward/0000-0001-9596-3552
FU Department of Pathology; Institute for Human Infection and Immunity; NIH
[HHSN272201000040I/HHSN27200004/D04]; NHMRC Australia Fellowship
FX The authors are grateful to the late Jean Pierre Digoutte for providing
Niakha virus strain DakArD 88909, to Gerald Campbell for his assistance
in the histological evaluation of stained brain sections, and to
Frederick A. Murphy for help in interpreting the electron micrographs of
the virus. This work was supported in part by the Department of
Pathology start up funds and a grant from the Institute for Human
Infection and Immunity to NV and NIH contract
HHSN272201000040I/HHSN27200004/D04 to RBT. ECH is supported by an NHMRC
Australia Fellowship. The authors have no conflicting financial
interests.
NR 28
TC 12
Z9 12
U1 1
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD SEP
PY 2013
VL 444
IS 1-2
BP 80
EP 89
DI 10.1016/j.virol.2013.05.035
PG 10
WC Virology
SC Virology
GA 210ZJ
UT WOS:000323873600011
PM 23773405
ER
PT J
AU Satheshkumar, PS
Chavre, J
Moss, B
AF Satheshkumar, P. S.
Chavre, James
Moss, Bernard
TI Role of the vaccinia virus O3 protein in cell entry can be fulfilled by
its Sequence flexible transmembrane domain
SO VIROLOGY
LA English
DT Article
DE Poxvirus entry; Membrane fusion; Entry-fusion complex; Transmembrane
protein; Mutagenesis
ID SURFACE HEPARAN-SULFATE; MEMBRANE-PROTEIN; FUSION COMPLEX; ESSENTIAL
COMPONENT; POXVIRUS ENTRY; MATURE VIRIONS; HOST-CELLS; L1 PROTEIN; GENE;
BINDS
AB The vaccinia virus O3 protein, a component of the entry-fusion complex, is encoded by all chordopox-viruses. We constructed truncation mutants and demonstrated that the transmembrane domain, which comprises two-thirds of this 35 amino acid protein, is necessary and sufficient for interaction with the entry-fusion complex and function in cell entry. Nevertheless, neither single amino acid substitutions nor alanine scanning mutagenesis revealed essential amino acids within the transmembrane domain. Moreover, replication-competent mutant viruses were generated by randomization of 10 amino acids of the transmembrane domain. Of eight unique viruses, two contained only two amino acids in common with wild type and the remainder contained one or none within the randomized sequence. Although these mutant viruses formed normal size plaques, the entry-fusion complex did not co-purify with the mutant O3 proteins suggesting a less stable interaction. Thus, despite low specific sequence requirements, the transmembrane domain is sufficient for function in entry. Published by Elsevier Inc.
C1 [Satheshkumar, P. S.; Chavre, James; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 33 North Dr,MSC 3210, Bethesda, MD 20892 USA.
EM bmoss@nih.gov
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX We thank Catherine Cotter for cell culture and Jason Laliberte and Karl
Erlandson for helpful discussions. The research was supported by
intramural funds of the National Institute of Allergy and Infectious
Diseases, National Institutes of Health.
NR 31
TC 4
Z9 6
U1 0
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD SEP
PY 2013
VL 444
IS 1-2
BP 148
EP 157
DI 10.1016/j.virol.2013.06.003
PG 10
WC Virology
SC Virology
GA 210ZJ
UT WOS:000323873600018
PM 23816434
ER
PT J
AU Dunn, LL
Boyer, PL
Clark, PK
Hughes, SH
AF Dunn, Linda L.
Boyer, Paul L.
Clark, Patrick K.
Hughes, Stephen H.
TI Mutations in HIV-1 reverse transcriptase cause misfolding and
miscleavage by the viral protease
SO VIROLOGY
LA English
DT Article
DE HIV-1; Reverse transcriptase; Protease; Stability; Differential scanning
fluorescence
ID IMMUNODEFICIENCY-VIRUS TYPE-1; RIBONUCLEASE-H ACTIVITY; DIMERIZATION;
INSTABILITY; SUBUNIT; VIRIONS
AB Previous work on mutations in the thumb of HIV-1 reverse transcriptase (RT) showed that the majority of the mutant RTs were degraded (by the viral protease) to various extents in virions. This degradation was, in most cases, temperature sensitive, and presumably was due to a partial unfolding of the protein at 37 degrees C.
We used recombinant proteins to investigate the effects of the mutations on the thermal stability and proteolytic degradation of RT.
Both subunits contribute to the stability of RT. In general, the differences in stability between the mutants and WT were greater if the mutation was in p51 rather than p66. Expressing the Pol polyprotein containing the RT mutants in Escherichia coli produced results similar to what was seen in virions; the mutant RTs were misfolded and/or degraded at 37 degrees C, but were better folded and processed at 30 degrees C. Published by Elsevier Inc.
C1 [Dunn, Linda L.; Boyer, Paul L.; Hughes, Stephen H.] NCI, HIV Drug Resistance Program, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
[Clark, Patrick K.] SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA.
RP Hughes, SH (reprint author), NCI, HIV Drug Resistance Program, Ctr Canc Res, NIH, POB B, Frederick, MD 21702 USA.
EM dunnli@mail.nih.gov; boyerp@mail.nih.gov; clarkpk@mail.nih.gov;
hughesst@mail.nih.gov
FU National Cancer Institute, NIH [HHSN26120080001E]; Intramural Research
Program of the National Institutes of Health (NIH), National Cancer
Institute, Center for Cancer Research
FX This study was supported in part by the Intramural Research Program of
the National Institutes of Health (NIH), National Cancer Institute,
Center for Cancer Research, and in part with federal funds from the
National Cancer Institute, NIH, under contract HHSN26120080001E.
NR 19
TC 5
Z9 5
U1 1
U2 9
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD SEP
PY 2013
VL 444
IS 1-2
BP 241
EP 249
DI 10.1016/j.virol.2013.06.017
PG 9
WC Virology
SC Virology
GA 210ZJ
UT WOS:000323873600028
PM 23850459
ER
PT J
AU Changula, K
Yoshida, R
Noyori, O
Marzi, A
Miyamoto, H
Ishijima, M
Yokoyama, A
Kajihara, M
Feldmann, H
Mweene, AS
Takada, A
AF Changula, Katendi
Yoshida, Reiko
Noyori, Osamu
Marzi, Andrea
Miyamoto, Hiroko
Ishijima, Mari
Yokoyama, Ayaka
Kajihara, Masahiro
Feldmann, Heinz
Mweene, Aaron S.
Takada, Ayato
TI Mapping of conserved and species-specific antibody epitopes on the Ebola
virus nucleoprotein
SO VIRUS RESEARCH
LA English
DT Article
DE Ebola virus; Nucleoprotein; Antibody epitope; Monoclonal antibody;
Synthetic peptide
ID LINKED-IMMUNOSORBENT-ASSAY; MONOCLONAL-ANTIBODIES; MARBURG VIRUSES;
GLYCOPROTEIN; PARTICLES; ANTIGEN; COMPLEX; VP40
AB Filoviruses (viruses in the genus Ebolavirus and Marburgvirus in the family Filoviridae) cause severe haemorrhagic fever in humans and nonhuman primates. Rapid, highly sensitive, and reliable filovirus-specific assays are required for diagnostics and outbreak control. Characterisation of antigenic sites in viral proteins can aid in the development of viral antigen detection assays such immunochromatography-based rapid diagnosis. We generated a panel of mouse monoclonal antibodies (mAbs) to the nucleoprotein (NP) of Ebola virus belonging to the species Zaire ebolavirus. The mAbs were divided into seven groups based on the profiles of their specificity and cross-reactivity to other species in the Ebolavirus genus. Using synthetic peptides corresponding to the Ebola virus NP sequence, the mAb binding sites were mapped to seven antigenic regions in the C-terminal half of the NP, including two highly conserved regions among all five Ebolavirus species currently known. Furthermore, we successfully produced species-specific rabbit antisera to synthetic peptides predicted to represent unique filovirus B-cell epitopes. Our data provide useful information for the development of Ebola virus antigen detection assays. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Changula, Katendi; Mweene, Aaron S.; Takada, Ayato] Univ Zambia, Sch Vet Med, Lusaka, Zambia.
[Changula, Katendi] SACIDS, Morogoro, Tanzania.
[Yoshida, Reiko; Noyori, Osamu; Miyamoto, Hiroko; Ishijima, Mari; Yokoyama, Ayaka; Kajihara, Masahiro; Takada, Ayato] Hokkaido Univ, Res Ctr Zoonosis Control, Div Global Epidemiol, Sapporo, Hokkaido 0010020, Japan.
[Marzi, Andrea; Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT USA.
RP Takada, A (reprint author), Hokkaido Univ, Res Ctr Zoonosis Control, Kita Ku, Kita 20 Nishi 10, Sapporo, Hokkaido 0010020, Japan.
EM atakada@czc.hokudai.ac.jp
RI YOSHIDA, Reiko/F-6883-2012
FU Japan Science and Technology Agency within the framework of the Science
and Technology Research Partnership for Sustainable Development
(SATREPS); Japan Initiative for Global Research Network on Infectious
Diseases (J-GRID); Ministry of Health, Labour and Welfare of Japan;
National Institute of Allergy and Infectious Diseases (NIAID), National
Institutes of Health (NIH).
FX We thank Dr. Hideki Ebihara (National Institute of Allergy and
Infectious Diseases, National Institutes of Health, Rocky Mountain
Laboratories) for valuable advice and Kim Barrymore for editing the
manuscript: This work was supported by the Japan Science and Technology
Agency within the framework of the Science and Technology Research
Partnership for Sustainable Development (SATREPS) and by the Japan
Initiative for Global Research Network on Infectious Diseases (J-GRID).
Funding was also provided by a Grant-in-Aid from the Ministry of Health,
Labour and Welfare of Japan, and in part by the Intramural Research
Program of the National Institute of Allergy and Infectious Diseases
(NIAID), National Institutes of Health (NIH).
NR 23
TC 8
Z9 8
U1 7
U2 37
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1702
J9 VIRUS RES
JI Virus Res.
PD SEP
PY 2013
VL 176
IS 1-2
BP 83
EP 90
DI 10.1016/j.virusres.2013.05.004
PG 8
WC Virology
SC Virology
GA 210TV
UT WOS:000323858500010
PM 23702199
ER
PT J
AU Levitt, AL
Singh, R
Cox-Foster, DL
Rajotte, E
Hoover, K
Ostiguy, N
Holmes, EC
AF Levitt, Abby L.
Singh, Rajwinder
Cox-Foster, Diana L.
Rajotte, Edwin
Hoover, Kelli
Ostiguy, Nancy
Holmes, Edward C.
TI Cross-species transmission of honey bee viruses in associated arthropods
SO VIRUS RESEARCH
LA English
DT Article
DE Deformed wing virus (DWV); Phylogenetic analysis; Virus detection; Apis
mellifera
ID DEFORMED-WING-VIRUS; MITES VARROA-DESTRUCTOR; ACUTE PARALYSIS VIRUS;
APIS-MELLIFERA L.; RNA VIRUSES; EVOLUTIONARY GENETICS; POPULATION
BIOLOGY; MUTATION-RATES; EMERGENCE; INFECTION
AB There are a number of RNA virus pathogens that represent a serious threat to the health of managed honey bees (Apis mellifera). That some of these viruses are also found in the broader pollinator community suggests the wider environmental spread of these viruses, with the potential for a broader impact on ecosystems. Studies on the ecology and evolution of these viruses in the arthropod community as a whole may therefore provide important insights into these potential impacts. We examined managed A. mellifera colonies, nearby non-Apis hymenopteran pollinators, and other associated arthropods for the presence of five commonly occurring picorna-like RNA viruses of honey bees - black queen cell virus, deformed wing virus, Israeli acute paralysis virus, Kashmir bee virus and sacbrood virus. Notably, we observed their presence in several arthropod species. Additionally, detection of negative-strand RNA using strand-specific RT-PCR assays for deformed wing virus and Israeli acute paralysis virus suggests active replication of deformed wing virus in at least six non-Apis species and active replication of Israeli acute paralysis virus in one non-Apis species. Phylogenetic analysis of deformed wing virus also revealed that this virus is freely disseminating across the species sampled in this study. In sum, our study indicates that these viruses are not specific to the pollinator community and that other arthropod species have the potential to be involved in disease transmission in pollinator populations. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Levitt, Abby L.] Penn State Univ, Huck Inst Life Sci, Intercoll Program Genet, University Pk, PA 16802 USA.
[Singh, Rajwinder; Cox-Foster, Diana L.; Rajotte, Edwin; Hoover, Kelli; Ostiguy, Nancy] Penn State Univ, Dept Entomol, University Pk, PA 16802 USA.
[Holmes, Edward C.] Univ Sydney, Sch Biol Sci, Sydney Emerging Infect & Biosecur Inst, Sydney, NSW 2006, Australia.
[Holmes, Edward C.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia.
[Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Hoover, K (reprint author), Penn State Univ, Dept Entomol, 501 ASI Bldg, University Pk, PA 16802 USA.
EM kxh25@psu.edu
OI Holmes, Edward/0000-0001-9596-3552
FU Alphawood Foundation; Pennsylvania Department of Agriculture [ME
446716]; Haagen Dazs Graduate Fellowship in Pollinator Health; NHMRC
Australia Fellowship
FX We thank Jeremy Fitzgerald and Christina Grozinger's group at the
Department of Entomology at The Pennsylvania State University for
assistance in collecting samples and the Penn State Genomics Core
Facility, University Park, PA for sequencing services. Funding provided
by the Alphawood Foundation, the Pennsylvania Department of Agriculture
(Grant No. ME 446716), and the Haagen Dazs Graduate Fellowship in
Pollinator Health. ECH is supported by an NHMRC Australia Fellowship.
NR 50
TC 26
Z9 30
U1 8
U2 96
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1702
EI 1872-7492
J9 VIRUS RES
JI Virus Res.
PD SEP
PY 2013
VL 176
IS 1-2
BP 232
EP 240
DI 10.1016/j.virusres.2013.06.013
PG 9
WC Virology
SC Virology
GA 210TV
UT WOS:000323858500027
PM 23845302
ER
PT J
AU Ozarslan, E
Koay, CG
Shepherd, TM
Komlosh, ME
Irfanoglu, MO
Pierpaoli, C
Basser, PJ
AF Oezarslan, Evren
Koay, Cheng Guan
Shepherd, Timothy M.
Komlosh, Michal E.
Irfanoglu, M. Okan
Pierpaoli, Carlo
Basser, Peter J.
TI Mean apparent propagator (MAP) MRI: A novel diffusion imaging method for
mapping tissue microstructure
SO NEUROIMAGE
LA English
DT Article
DE Diffusion; Propagator; ODF; Return-to-origin; Non-Gaussianity;
Anisotropy; Volume; Hermite; SHORE; Generalized DTI; GDTI
ID NON-GAUSSIAN DIFFUSION; GENERALIZED DIFFUSION; FIELD GRADIENT; WEIGHTED
MRI; SPHERICAL DECONVOLUTION; PROBABILITY DENSITY; RAT HIPPOCAMPUS; AXON
DIAMETER; SPIN ECHOES; HUMAN BRAIN
AB Diffusion-weighted magnetic resonance (MR) signals reflect information about underlying tissue microstructure and cytoarchitecture. We propose a quantitative, efficient, and robust mathematical and physical framework for representing diffusion-weighted MR imaging (MRI) data obtained in "q-space," and the corresponding "mean apparent propagator (MAP)" describing molecular displacements in "r-space." We also define and map novel quantitative descriptors of diffusion that can be computed robustly using this MAP-MRI framework.
We describe efficient analytical representation of the three-dimensional q-space MR signal in a series expansion of basis functions that accurately describes diffusion in many complex geometries. The lowest order term in this expansion contains a diffusion tensor that characterizes the Gaussian displacement distribution, equivalent to diffusion tensor MRI (DTI). Inclusion of higher order terms enables the reconstruction of the true average propagator whose projection onto the unit "displacement" sphere provides an orientational distribution function (ODF) that contains only the orientational dependence of the diffusion process. The representation characterizes novel features of diffusion anisotropy and the non-Gaussian character of the three-dimensional diffusion process. Other important measures this representation provides include the return-to-the-origin probability (RTOP), and its variants for diffusion in one- and two-dimensions-the return-to-the-plane probability (RTPP), and the return-to-the-axis probability (RTAP), respectively. These zero net displacement probabilities measure the mean compartment (pore) volume and cross-sectional area in distributions of isolated pores irrespective of the pore shape.
MAP-MRI represents a new comprehensive framework to model the three-dimensional q-space signal and transform it into diffusion propagators. Experiments on an excised marmoset brain specimen demonstrate that MAP-MRI provides several novel, quantifiable parameters that capture previously obscured intrinsic features of nervous tissue microstructure. This should prove helpful for investigating the functional organization of normal and pathologic nervous tissue. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Oezarslan, Evren; Komlosh, Michal E.; Irfanoglu, M. Okan; Pierpaoli, Carlo; Basser, Peter J.] NICHD, Sect Tissue Biophys & Biomimet, PPITS, NIH, Bethesda, MD 20892 USA.
[Oezarslan, Evren; Komlosh, Michal E.; Irfanoglu, M. Okan] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA.
[Oezarslan, Evren] Harvard Univ, Brigham & Womens Hosp, Dept Radiol, Sch Med, Boston, MA 02215 USA.
[Koay, Cheng Guan] Univ Wisconsin, Dept Med Phys, Madison, WI 53705 USA.
[Shepherd, Timothy M.] NYU, Dept Radiol, Langone Med Ctr, New York, NY 10016 USA.
RP Ozarslan, E (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Radiol, Sch Med, Boston, MA 02215 USA.
EM evren@bwh.harvard.edu
RI Ozarslan, Evren/B-4858-2013
OI Ozarslan, Evren/0000-0003-0859-1311
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD); National
Institutes of Health (NIH); Department of Defense in the Center for
Neuroscience and Regenerative Medicine (CNRM); Henry M. Jackson
Foundation (HJF); NIH [IRCMH090912-01, R01MH074794]
FX The authors gratefully acknowledge Drs. John D. Newman and Afonso C.
Silva for the marmoset brain specimen and Liz Salak for editing the
manuscript. Special thanks to Jian Cheng for pointing out an error in
(Ozarslan et al., 2009c). Support for this work included funding from:
(i) the Intramural Research Program of the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (NICHD), the
National Institutes of Health (NIH), and (ii) the Department of Defense
in the Center for Neuroscience and Regenerative Medicine (CNRM) and the
Henry M. Jackson Foundation (HJF). (iii) CGK was supported in part by
NIH grant no. IRCMH090912-01. (iv) EO was supported in part by NIH
R01MH074794.
NR 74
TC 49
Z9 49
U1 2
U2 36
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 SEP
PY 2013
VL 78
BP 16
EP 32
DI 10.1016/j.neuroimage.2013.04.016
PG 17
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 165MV
UT WOS:000320488900003
PM 23587694
ER
PT J
AU Warren, K
AF Warren, K.
TI FETAL ALCOHOL SPECTRUM DISORDERS: STRANGE BEGINNINGS TO CUTTING EDGE
RESEARCH ESBRA & ISBRA JOINT SYMPOSIUM
SO ALCOHOL AND ALCOHOLISM
LA English
DT Meeting Abstract
C1 [Warren, K.] NIAAA, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0735-0414
J9 ALCOHOL ALCOHOLISM
JI Alcohol Alcohol.
PD SEP
PY 2013
VL 48
SU 1
BP 18
EP 19
PG 2
WC Substance Abuse
SC Substance Abuse
GA 204EP
UT WOS:000323348200079
ER
PT J
AU Leggio, L
AF Leggio, L.
TI STUDYING THE ROLE OF FEEDING-RELATED PATHWAYS IN ALCOHOLISM VIA HUMAN
LABORATORY STUDIES
SO ALCOHOL AND ALCOHOLISM
LA English
DT Meeting Abstract
C1 [Leggio, L.] NIAAA, Lab Clin & Translat Studies, Bethesda, MD USA.
RI Leggio, Lorenzo/M-2972-2016
NR 0
TC 1
Z9 1
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0735-0414
J9 ALCOHOL ALCOHOLISM
JI Alcohol Alcohol.
PD SEP
PY 2013
VL 48
SU 1
BP 27
EP 27
PG 1
WC Substance Abuse
SC Substance Abuse
GA 204EP
UT WOS:000323348200119
ER
PT J
AU Ramchandani, V
AF Ramchandani, V.
TI CHARACTERIZATION OF OPERANT INTRAVENOUS ALCOHOL SELF-ADMINISTRATION IN
HUMANS
SO ALCOHOL AND ALCOHOLISM
LA English
DT Meeting Abstract
C1 [Ramchandani, V.] NIAAA, Lab Clin & Translat Studies, Sect Human Psychopharmacol, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0735-0414
J9 ALCOHOL ALCOHOLISM
JI Alcohol Alcohol.
PD SEP
PY 2013
VL 48
SU 1
BP 27
EP 27
PG 1
WC Substance Abuse
SC Substance Abuse
GA 204EP
UT WOS:000323348200118
ER
PT J
AU van Meurs, JBJ
Pare, G
Schwartz, SM
Hazra, A
Tanaka, T
Vermeulen, SH
Cotlarciuc, I
Yuan, X
Malarstig, A
Bandinelli, S
Bis, JC
Morn, H
Brown, MJ
Chen, C
Chen, YD
Clarke, RJ
Dehghan, A
Erdmann, J
Ferrucci, L
Hamsten, A
Hofman, A
Hunten, DJ
Goel, A
Johnson, AD
Kathiresan, S
Kampman, E
Kiel, DP
Kiemeney, LA
Chambers, JC
Kraft, P
Lindemans, J
McKnight, B
Nelson, CP
O'Donnell, CJ
Psaty, BM
Ridken, PM
Rivadeneira, F
Rose, LM
Seedoif, U
Siscovick, DS
Schunkert, H
Selhub, J
Ueland, PM
Vollenweiden, P
Waeben, G
Waterworth, DM
Watkins, H
Witteman, JCM
den Heijen, M
Jacques, P
Uitterlinden, AG
Koonet, JS
Rader, DJ
Reilly, MP
Moose, V
Chasman, DI
Samani, NJ
Ahmadi, KR
AF van Meurs, Joyce B. J.
Pare, Guillaume
Schwartz, Stephen M.
Hazra, Aditi
Tanaka, Toshiko
Vermeulen, Sita H.
Cotlarciuc, Ioana
Yuan, Xin
Malarstig, Anders
Bandinelli, Stefania
Bis, Joshua C.
Morn, Henk
Brown, Morris J.
Chen, Constance
Chen, Yii-Der
Clarke, Robert J.
Dehghan, Abbas
Erdmann, Jeanette
Ferrucci, Luigi
Hamsten, Anders
Hofman, Albert
Hunten, David J.
Goel, Anuj
Johnson, Andrew D.
Kathiresan, Secar
Kampman, Ellen
Kiel, Douglas P.
Kiemeney, Lamberius Aim
Chambers, John C.
Kraft, Peter
Lindemans, Jan
McKnight, Barbara
Nelson, Christopher P.
O'Donnell, Christopher J.
Psaty, Bruce M.
Ridken, Paul M.
Rivadeneira, Fernando
Rose, Lynda M.
Seedoif, Udo
Siscovick, David S.
Schunkert, Heribert
Selhub, Jacob
Ueland, Per M.
Vollenweiden, Peter
Waeben, Gerard
Waterworth, Dawn M.
Watkins, Hugh
Witteman, Jacqueline C. M.
den Heijen, Martin
Jacques, Paul
Uitterlinden, Andre G.
Koonet, Jaspal S.
Rader, Dan J.
Reilly, Muredach P.
Moose, Vincent
Chasman, Daniel I.
Samani, Nilesh J.
Ahmadi, Kourosh R.
TI Common genetic loci influencing plasma homocysteine concentrations and
their effect on risk of coronary artery disease
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CARDIOVASCULAR-DISEASE; MENDELIAN
RANDOMIZATION; HEART-DISEASE; EXPRESSION; METAANALYSIS; MTHFR;
POLYMORPHISM; WOMEN; IDENTIFICATION
AB Background: The strong observational association between total homocysteine (tHcy) concentrations and risk of coronary artery disease (CAD) and the null associations in the homocysteinelowering trials have prompted the need to identify genetic variants associated with homocysteine concentrations and risk of CAD.
Objective: We tested whether common genetic polymorphisms associated with variation in tlicy are also associated with CAD.
Design: We conducted a meta-analysis of genome-wide association studies (GWAS) on tHcy concentrations in 44,147 individuals of European descent. Polymolphisms associated with tHcy (P < 10(-8)) were tested for association with CAD in 31,400 cases and 92,927 controls.
Results: Common variants at 13 loci, explaining 5.9% of the variation in tHcy, were associated with tHcy concentrations, including 6 novel loci in or near MMACHC (2.1 X 10(-9)), SLC17A3 (1.0 x 10(-8)), GTPB10 (1.7 X 10(-8)), CUBN (7.5 X 10(-1)), HNFlA (1.2 x 10(-12)), and FUT2 (6.6 x 10(-9)), and variants previously reported at or near the MTHFR, MTR, CPS1, MUT, NOX4, DPEP1, and CBS genes. Individuals within the highest 10% of the genotype risk score (GRS) had 3-gmol/L higher mean tHcy concentrations than did those within the lowest 10% of the GRS (P = 1 X 10(-36)). The GRS was not associated with risk of CAD (OR: 1.01; 95% CI: 0.98, 1.04; P = 0.49).
Conclusions: We identified several novel loci that influence plasma tHcy concentrations. Overall, common genetic variants that influence plasma tHcy concentrations are not associated with risk of CAD in white populations, which further refutes the causal relevance of moderately elevated tHey concentrations and tHcy-related pathways for CAD.
C1 [van Meurs, Joyce B. J.; Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Dehghan, Abbas; Hofman, Albert; Rivadeneira, Fernando; Witteman, Jacqueline C. M.; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[van Meurs, Joyce B. J.; Rivadeneira, Fernando] Netherlands Consortium Hlth Aging, Netherlands Genom Initiat, Leiden, Netherlands.
[Pare, Guillaume] McMaster Univ, Dept Pathol, Hamilton, ON, Canada.
[Schwartz, Stephen M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Hazra, Aditi; Chen, Constance; Hunten, David J.; Kraft, Peter] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dep Med, Boston, MA 02115 USA.
[Hazra, Aditi; Chen, Constance; Hunten, David J.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Tanaka, Toshiko; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Vermeulen, Sita H.] Radboud Univ Nijmegen, Med Ctr, Dept Hlth Evidence, Nijmegen, Netherlands.
[Cotlarciuc, Ioana; Ahmadi, Kourosh R.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England.
[Yuan, Xin; Waterworth, Dawn M.; Moose, Vincent] GlaxoSmithKline, Div Genet, King Of Prussia, PA USA.
[Yuan, Xin; Vollenweiden, Peter; Waeben, Gerard; Waterworth, Dawn M.; Moose, Vincent] Univ Lausanne, Dept Med, Div Internal Med, Lausanne, Switzerland.
[Yuan, Xin; Vollenweiden, Peter; Waeben, Gerard; Waterworth, Dawn M.; Moose, Vincent] Univ Lausanne, Ctr Hosp Univ Vaudois, Lausanne, Switzerland.
[Malarstig, Anders; Hamsten, Anders] Karolinska Inst, Atherosclerosis Res Unit, Stockholm, Sweden.
[Bandinelli, Stefania] Azienda Sanitaria Firenze, Geriatr Unit, Florence, Italy.
Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands.
[Brown, Morris J.] Univ Cambridge, Clin Pharmacol Unit, Cambridge, England.
[Chen, Yii-Der] Cedars Sinai Med Ctr, Med Genet Res Inst, Los Angeles, CA 90048 USA.
[Clarke, Robert J.] Univ Oxford, Clin Trial Serv Unit, Oxford OX1 2JD, England.
[Clarke, Robert J.] Univ Oxford, Epidemiol Studies Unit, Oxford OX1 2JD, England.
[Erdmann, Jeanette; Schunkert, Heribert] Univ Lubeck, Med Klin 2, Lubeck, Germany.
[Goel, Anuj; Watkins, Hugh] Univ Oxford, Dept Cardiovasc Med, Oxford OX1 2JD, England.
[Selhub, Jacob; Jacques, Paul] Tufts Univ, Vitamin Metab & Aging Lab, Boston, MA 02111 USA.
[Selhub, Jacob; Jacques, Paul] Tufts Univ, Nutrit Epidemiol Program, Boston, MA 02111 USA.
[Johnson, Andrew D.; Kiel, Douglas P.; O'Donnell, Christopher J.; Jacques, Paul] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Kathiresan, Secar] Cardiovasc Res Ctr, Boston, MA USA.
[Kathiresan, Secar] Div Cardiol, Boston, MA USA.
[Kampman, Ellen] Wageningen Univ, Div Human Nutr, NL-6700 AP Wageningen, Netherlands.
[Kiel, Douglas P.] Hebrew SeniorLife Inst Aging Res, Boston, MA USA.
[Kiel, Douglas P.] Harvard Univ, Sch Med, Boston, MA USA.
[Koonet, Jaspal S.] Natl Heart & Lung Inst, Bethesda, MD USA.
[McKnight, Barbara] Imperial Coll London, London, England.
[McKnight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Nelson, Christopher P.; Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.
[Nelson, Christopher P.; Samani, Nilesh J.] Glenfield Hosp, NIHR, Leicester Cardiovascular Biomed Res Unit, Leicester, Leics, England.
[Reilly, Muredach P.] Univ Washington, Cardiovascular Hlth Res Unit, Dept Med, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Cardiovascular Hlth Res Unit, Dept Epidemiol, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Cardiovascular Hlth Res Unit, Dept Hlth Serv, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA.
[Ridken, Paul M.; Rose, Lynda M.; Chasman, Daniel I.] Harvard Univ, Sch Med, Dept Prevent Med, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Seedoif, Udo] Univ Munster, Inst Arterioskleroseforsch, D-48149 Munster, Germany.
[Ueland, Per M.] Univ Bergen Haukeland, Bergen, Norway.
[Ueland, Per M.] Bergen Univ Hosp, Bergen, Norway.
[Rader, Dan J.; Reilly, Muredach P.] Univ Penn, Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Rader, Dan J.; Reilly, Muredach P.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Samani, Nilesh J.] Leicester NTHR Biomed Res Unit Cardiovasc Dis, Leicester, Leics, England.
[Erdmann, Jeanette; Schunkert, Heribert] Univ Lubeck, Deutsch Zentrum Herz Kreislauf Forschung, Lubeck, Germany.
[den Heijen, Martin] Vrije Univ Amsterdam Med Ctr, Dept Internal Med, Amsterdam, Netherlands.
[Ahmadi, Kourosh R.] Univ Surrey, Dept Nutr & Metab, Fac Hlth & Med Sci, Guildford GU2 5XH, Surrey, England.
RP Ahmadi, KR (reprint author), Univ Surrey, Dept Nutr & Metab, Fac Hlth & Med Sci, Guildford GU2 5XH, Surrey, England.
EM k.ahmadi@surrey.co.uk
RI Colaus, PsyColaus/K-6607-2013; Kiemeney, Lambertus/D-3357-2009; Erdmann,
Jeanette/P-7513-2014; Ueland, Per/C-7340-2013; den Heijer,
Martin/J-8036-2015; Kampman, E./H-8057-2014; Rivadeneira,
Fernando/O-5385-2015; Vermeulen, H.H.M./L-4716-2015; Johnson,
Andrew/G-6520-2013;
OI Kiemeney, Lambertus/0000-0002-2368-1326; Erdmann,
Jeanette/0000-0002-4486-6231; Kiel, Douglas/0000-0001-8474-0310; den
Heijer, Martin/0000-0003-3620-5617; Rivadeneira,
Fernando/0000-0001-9435-9441; Blom, Henk/0000-0001-5202-9241; Schwartz,
Stephen/0000-0001-7499-8502; Seedorf, Udo/0000-0003-4652-5358; Watkins,
Hugh/0000-0002-5287-9016; Dehghan, Abbas/0000-0001-6403-016X
FU Netherlands Consortium for Healthy Aging, Rotterdam, Leiden the
Netherlands; Department of Pathology; McMaster University, Hamilton,
Canada; Cardiovascular Health Research Unit, Department of Epidemiology,
University of Washington, Seattle, WA; Channing Laboratory, Department
of Medicine, Brigham; Women's Hospital, Harvard Medical School and
Department of Epidemiology, Harvard School of Public Health, Boston;
Clinical Research Branch, National Institute on Aging, Baltimore, MD;
Department for Health Evidence, Radboud University Medical Centre,
Nijmegen, the Netherlands; Department of Twin Research and Genetic
Epidemiology, King's College London, London, United Kingdom; Genetics
Division, GlaxoSmithKline, King of Prussia, PA; Department of Medicine,
Division of Internal Medicine, Centre Hospitalier Universitaire Vaudois
and University of Lausanne, Lausanne, Switzerland
FX From the Departments of Internal Medicine (JBJvM, FR, and AGU),
Epidemiology (AD, A Hofman, FR, JCMVV, and AGU), and Clinical Chemistry
(IL), Erasmus MC, Rotterdam, the Netherlands; the Netherlands Genomics
Initiative, sponsored by the Netherlands Consortium for Healthy Aging,
Rotterdam, Leiden the Netherlands (JBJvM and FR); the Department of
Pathology, McMaster University, Hamilton, Canada (GP); the
Cardiovascular Health Research Unit, Department of Epidemiology,
University of Washington, Seattle, WA (SMS); the Channing Laboratory,
Department of Medicine, Brigham and Women's Hospital, Harvard Medical
School and Department of Epidemiology, Harvard School of Public Health,
Boston (AH, CC, DJH, and PK); the Clinical Research Branch, National
Institute on Aging, Baltimore, MD (TT, and LF); the Department for
Health Evidence, Radboud University Medical Centre, Nijmegen, the
Netherlands (SHY and LALMK); the Department of Twin Research and Genetic
Epidemiology, King's College London, London, United Kingdom (IC and
KRA); the Genetics Division, GlaxoSmithKline, King of Prussia, PA (XY,
DMW, and VM); the Department of Medicine, Division of Internal Medicine,
Centre Hospitalier Universitaire Vaudois and University of Lausanne,
Lausanne, Switzerland (XY, PV, GW, DIVIW, and VM); the Atherosclerosis
Research Unit, Karolinska Institute, Stockholm, Sweden (AM and A
Hamsten); the Geriatric Unit, Azienda Sanitaria Firenze, Florence, Italy
(SB); the VU Medical Centre, Amsterdam, the Netherlands (HB); the
Clinical Pharmacology Unit, University of Cambridge, Cambridge, United
Kingdom (MJB); the Medical Genetics Research Institute, Cedars-Sinai
Medical Centre, Los Angeles, CA (Y-DC); the Clinical Trial Service Unit
and Epidemiological Studies Unit, University of Oxford, United Kingdom
(RJC); Medizinische Klinik It, Universitat zu Liibeck, Liibeck, Germany
(JE and HS); the Department of Cardiovascular Medicine, University of
Oxford, United Kingdom (AG and HW); the Vitamin Metabolism and Aging
Laboratory and Nutritional Epidemiology Program, Tufts University,
Boston, MA (JS and PJ); the Framingham Heart Study, National Heart,
Lung, and Blood Institute, Framingham, MA (ADJ, DPK, CJO, and PJ); the
Cardiovascular Research Center and Cardiology Division, Boston, MA (SK);
the Division of Human Nutrition, Wageningen University, Wageningen, the
Netherlands (EK); the Hebrew Senior Life Institute for Aging Research
and Harvard Medical School, Boston, MA (DPK); the Department of
Epidemiology and Biostatistics (JCC) and the National Heart and Lung
Institute (JSK), Imperial College of London, United Kingdom; the
Department of Biostatistics, University of Washington, Seattle, WA (BM);
the Department of Cardiovascular Sciences, University of Leicester,
Leicester (CPN and NJS) and NIHR Leicester Cardiovascular Biomedical
Research Unit, Glenfield Hospital, Leicester, United Kingdom (CPN and
NJS); the Cardiovascular Health Research Unit, Departments of Medicine,
Epidemiology, and Health Services, University of Washington and the
Group Health Research Institute, Group Health Cooperative, Seattle, WA
(BMP); the Division of Preventive Medicine, Brigham and Women's
Hospital, Harvard Medical School, Boston, MA (PMR, LMR, and DIC); the
Institut fur Arterioskleroseforschung an der Universitat Miinster,
Miinster, Germany (US); the University of Bergen/ Haukeland, University
Hospital Bergen, Bergen, Norway (PMU); the Cardiovascular Institute and
Division of Translational Medicine and Human Genetics, Department of
Medicine, University of Pennsylvania School of Medicine, Philadelphia; ,
PA (DJR and MPR); Leicester NTHR Biomedical Research Unit in
Cardiovascular Disease, Leicester, United Kingdom (NJS); the Deutsches
Zentrum fur Herz-Kreislauf-Forschung, Universitat zu Liibeck, Lubeck,
Germany (TB and HS); the Department of Internal Medicine, VU Medical
Center, Amsterdam, the Netherlands (MdH); and the Department of
Nutrition and Metabolism, Faculty of Health and Medical Sciences,
University of Surrey, Guildford, United Kingdom (KRA).
NR 47
TC 40
Z9 40
U1 0
U2 17
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD SEP
PY 2013
VL 98
IS 3
BP 668
EP 676
DI 10.3945/ajcn.112.044545
PG 9
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 206OT
UT WOS:000323532700007
PM 23824729
ER
PT J
AU Miller, PE
Cross, AJ
Subar, AF
Krebs-Smith, SM
Park, Y
Powell-Wiley, T
Hollenbeck, A
Reedy, J
AF Miller, Paige E.
Cross, Amanda J.
Subar, Amy F.
Krebs-Smith, Susan M.
Park, Yikyung
Powell-Wiley, Tiffany
Hollenbeck, Albert
Reedy, Jill
TI Comparison of 4 established DASH diet indexes: examining associations of
index scores and colorectal cancer
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID FOOD FREQUENCY QUESTIONNAIRES; HEALTH-AMERICAN-ASSOCIATION;
RETIRED-PERSONS DIET; NATIONAL-INSTITUTES; BLOOD-PRESSURE; HYPERTENSION;
RISK; PATTERNS; ADHERENCE; DISEASE
AB Background: Multiple diet indexes have been developed to capture the Dietary Approaches to Stop Hypertension (DASH) dietary pattern and examine relations with health outcomes but have not been compared within the same study population to our knowledge.
Objective: We compared 4 established DASH indexes and examined associations with colorectal cancer.
Design: Scores were generated from a food-frequency questionnaire in the NIH-AARP Diet and Health Study (n = 491,841). Separate indexes defined by Dixon (7 food groups, saturated fat, and alcohol), Mellen (9 nutrients), Fung (7 food groups and sodium), and Gunther (8 food groups) were used. HRs and 95% CIs for colorectal cancer were generated by using Cox proportional hazard models.
Results: From 1995 through 2006, 6752 incident colorectal cancer cases were ascertained. In men, higher scores were associated with reduced colorectal cancer incidence by comparing highest to lowest quintiles for all indexes as follows: Dixon (HR: 0.77; 95% CI: 0.69, 0.87), Mellen (HR: 0.78; 95% CI: 031, 0.86), Fung (HR: 0.75; 95% CI: 0.68, 0.83), and Gunther (HR: 0.81; 95% CI: 0.74, 0.90). Higher scores in women were inversely associated with colorectal cancer incidence by using methods defined by Mellen (HR: 0.79; 95% CI: 0.68, 0.91), Fung (HR: 0.84; 95% CI: 0.73, 0.96), and Gunther (HR: 0.84; 95% CI: 0.73.0.97) but not Dixon (BR: 1.01; 95% CI: 0.80, 1.28).
Conclusion: The consistency in findings, particularly in men, suggests that all indexes capture an underlying construct inherent in the DASH dietary pattern, although the specific index used can affect results.
C1 [Miller, Paige E.] NCI, Canc Prevent Fellowship Program, Rockville, MD USA.
[Cross, Amanda J.; Park, Yikyung] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Subar, Amy F.; Krebs-Smith, Susan M.; Reedy, Jill] NCI, Div Canc Control & Populat Sci, Rockville, MD USA.
[Miller, Paige E.] Exponent Inc, Ctr Epidemiol Biostat & Computat Biol, Chicago, IL USA.
[Powell-Wiley, Tiffany] NHLBI, Cardiovasc & Pulm Branch, Bethesda, MD 20892 USA.
[Hollenbeck, Albert] AARP, Washington, DC USA.
RP Miller, PE (reprint author), Exponent Inc, 525 West Monroe St,Suite 1050, Chicago, IL 60661 USA.
EM pmiller@exponent.com
OI Park, Yikyung/0000-0002-6281-489X
FU Cancer Prevention Fellowship Program; Intramural Research Program,
National Cancer Institute, NIH
FX Supported by the Cancer Prevention Fellowship Program and the Intramural
Research Program, National Cancer Institute, NIH.
NR 30
TC 18
Z9 18
U1 0
U2 11
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD SEP
PY 2013
VL 98
IS 3
BP 794
EP 803
DI 10.3945/ajcn.113.063602
PG 10
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 206OT
UT WOS:000323532700022
PM 23864539
ER
PT J
AU Folio, LR
Sandouk, A
Huang, JX
Solomon, JM
Apolo, AB
AF Folio, Les R.
Sandouk, Aline
Huang, Jiaxin
Solomon, Jeffrey M.
Apolo, Andrea B.
TI Consistency and Efficiency of CT Analysis of Metastatic Disease:
Semiautomated Lesion Management Application Within a PACS
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Article
DE metastatic cancer; quantitative imaging; RECIST; tumor assessment;
volumetric measurements
ID IMAGE REGISTRATION; TUMOR SEGMENTATION; SOLID TUMORS; LUNG-CANCER;
CLASSIFICATION; VARIABILITY; PULMONARY; SCANS
AB OBJECTIVE. The purpose of this study was to evaluate the success, consistency, and efficiency of a semiautomated lesion management application within a PACS in the analysis of metastatic lesions in serial CT examinations of cancer patients.
MATERIALS AND METHODS. Two observers using baseline and follow-up CT data independently reviewed 93 target lesions (17 lung, five liver, 71 lymph node) in 50 patients with either metastatic bladder or prostate cancer. The observers measured the longest axis (or short axis for lymph nodes) of each lesion and made Response Evaluation Criteria in Solid Tumors (RECIST) determinations using manual and lesion management application methods. The times required for examination review, RECIST calculations, and data input were recorded. The Wilcoxon signed rank test was used to assess time differences, and Bland-Altman analysis was used to assess interobserver agreement within the manual and lesion management application methods. Percentage success rates were also reported.
RESULTS. With the lesion management application, most lung and liver lesions were semiautomatically segmented. Comparison of the lesion management application and manual methods for all lesions showed a median time saving of 45% for observer 1 (p < 0.05) and 28% for observer 2 (p = 0.05) on follow-up scans versus 28% for observer 1 (p < 0.05) and 9% for observer 2 (p = 0.087) on baseline scans. Variability of measurements showed mean percentage change differences of only 8.9% for the lesion management application versus 26.4% for manual measurements.
CONCLUSION. With the lesion management application method, most lung and liver lesions were successfully segmented semiautomatically; the results were more consistent between observers; and assessment of tumor size was faster than with the manual method.
C1 [Folio, Les R.; Sandouk, Aline; Huang, Jiaxin; Solomon, Jeffrey M.] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
[Solomon, Jeffrey M.] Expert Image Anal LLC, Potomac, MD USA.
[Apolo, Andrea B.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Folio, LR (reprint author), NIH, Dept Radiol & Imaging Sci, Ctr Clin, 10 Ctr Dr,Bldg 10,Rm 1C340, Bethesda, MD 20892 USA.
EM les.folio@nih.gov
FU Intramural Research Program of the National Institutes of Health
FX Supported in part by the Intramural Research Program of the National
Institutes of Health.
NR 31
TC 7
Z9 7
U1 2
U2 11
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
EI 1546-3141
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD SEP
PY 2013
VL 201
IS 3
BP 618
EP 625
DI 10.2214/AJR.12.10136
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 207LP
UT WOS:000323601500041
PM 23971455
ER
PT J
AU Lennartz, F
Hoenen, T
Lehmann, M
Groseth, A
Garten, W
AF Lennartz, Frank
Hoenen, Thomas
Lehmann, Maria
Groseth, Allison
Garten, Wolfgang
TI The role of oligomerization for the biological functions of the
arenavirus nucleoprotein
SO ARCHIVES OF VIROLOGY
LA English
DT Article
ID VIRUS-LIKE PARTICLES; VIRAL-RNA SYNTHESIS; MATRIX PROTEIN-Z;
LASSA-VIRUS; IMMUNE SUPPRESSION; TERMINAL REGION; REPLICATION; NP;
TRANSCRIPTION; REVEALS
AB The Lassa virus nucleoprotein (NP) is a multifunctional protein that plays an essential role in many aspects of the viral life cycle, including RNA encapsidation, viral transcription and replication, recruitment of ribonucleoprotein complexes to viral budding sites, and inhibition of the host cell interferon response. While it is known that NP is capable of forming oligomers, both the oligomeric state of NP in mammalian cells and the significance of NP oligomerization for its various functions remain unclear. Here, we demonstrate that Lassa virus NP solely forms trimers upon expression in mammalian cells. Using a minigenome assay we show that mutants that are not able to form stable trimers are no longer functional during transcription and/or replication of the minigenome, indicating that NP trimerization is essential for transcription and/or replication of the viral genome. However, mutations leading to destabilization of the NP trimer did not impact the incorporation of NP into virus-like particles or its ability to suppress interferon-induced gene expression, two important functions of arenavirus NP.
C1 [Lennartz, Frank; Hoenen, Thomas; Groseth, Allison; Garten, Wolfgang] Univ Marburg, Inst Virol, D-35043 Marburg, Germany.
[Hoenen, Thomas; Groseth, Allison] NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT 59840 USA.
[Lehmann, Maria] Bernhard Nocht Inst Trop Med, Dept Virol, D-20359 Hamburg, Germany.
RP Garten, W (reprint author), Univ Marburg, Inst Virol, Hans Meerwein Str 2, D-35043 Marburg, Germany.
EM garten@staff.uni-marburg.de
OI Hoenen, Thomas/0000-0002-5829-6305
FU Deutsche Forschungsgemeinschaft [SPP1175, SFB593]; Stiftung zur
Forderung von Forschung und Lehre am Fachbereich Medizin der
Philipps-Universitat Marburg; Studienstiftung des deutschen Volkes;
Schering Foundation; Canadian Institutes of Health Research; NIH, NIAID
FX We thank Thomas Strecker for critical manuscript review and Petra
Neubauer-Radel for expert technical assistance. We further thank Stephan
Becker (Philipps University Marburg), Thomas Strecker (Philipps
University Marburg) and Takashi Fujita (Kyoto University) for kindly
providing plasmids. This work was supported by grants from the Deutsche
Forschungsgemeinschaft (SPP1175 and SFB593), the "Stiftung zur Forderung
von Forschung und Lehre am Fachbereich Medizin der Philipps-Universitat
Marburg", the "Studienstiftung des deutschen Volkes" (F. L.), the
Schering Foundation (T. H.), the Canadian Institutes of Health Research
(A. G.), and in part by the Intramural Research Program of the NIH,
NIAID.
NR 35
TC 3
Z9 3
U1 0
U2 3
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0304-8608
J9 ARCH VIROL
JI Arch. Virol.
PD SEP
PY 2013
VL 158
IS 9
BP 1895
EP 1905
DI 10.1007/s00705-013-1684-9
PG 11
WC Virology
SC Virology
GA 208CS
UT WOS:000323654600007
PM 23553456
ER
PT J
AU Lorenzo, FR
Yang, CZ
Lanikova, L
Butros, L
Zhuang, ZP
Prchal, JT
AF Lorenzo, Felipe R.
Yang, Chunzhang
Lanikova, Lucie
Butros, Linda
Zhuang, Zhengping
Prchal, Josef T.
TI Novel compound VHL heterozygosity (VHL T124A/L188V) associated with
congenital polycythaemia
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Letter
DE polycythaemia; erythrocytosis; mutations; molecular haematology;
genetics
ID CHUVASH POLYCYTHEMIA; MUTATION; ERYTHROPOIETIN; ERYTHROCYTOSIS;
PARAGANGLIOMA; RECEPTOR; GENE
C1 [Lorenzo, Felipe R.; Lanikova, Lucie; Prchal, Josef T.] Univ Utah, Div Hematol, Salt Lake City, UT 84112 USA.
[Lorenzo, Felipe R.; Lanikova, Lucie; Prchal, Josef T.] VA Hlth Care, Salt Lake City, UT USA.
[Yang, Chunzhang; Zhuang, Zhengping] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Lanikova, Lucie] Palacky Univ, Fac Med & Dent, Dept Biol, CR-77147 Olomouc, Czech Republic.
[Butros, Linda] Univ New Mexico, Albuquerque, NM 87131 USA.
RP Lorenzo, FR (reprint author), Univ Utah, Div Hematol, Salt Lake City, UT 84112 USA.
EM josef.prchal@hsc.utah.edu
RI Lanikova, Lucie/F-7720-2013
FU NCI NIH HHS [P01 CA108671, P01CA108671]
NR 10
TC 5
Z9 5
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1048
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD SEP
PY 2013
VL 162
IS 6
BP 851
EP 853
DI 10.1111/bjh.12431
PG 3
WC Hematology
SC Hematology
GA 209BL
UT WOS:000323728600018
PM 23772956
ER
PT J
AU Kolesar, JM
Traynor, AM
Holen, KD
Hoang, T
Seo, S
Kim, K
Alberti, D
Espinoza-Delgado, I
Wright, JJ
Wilding, G
Bailey, HH
Schelman, WR
AF Kolesar, Jill M.
Traynor, Anne M.
Holen, Kyle D.
Hoang, Tien
Seo, Songwon
Kim, KyungMann
Alberti, Dona
Espinoza-Delgado, Igor
Wright, John J.
Wilding, George
Bailey, Howard H.
Schelman, William R.
TI Vorinostat in combination with bortezomib in patients with advanced
malignancies directly alters transcription of target genes
SO CANCER CHEMOTHERAPY AND PHARMACOLOGY
LA English
DT Article
DE SAHA; Vorinostat; PS-341; Bortezomib; Phase I
ID SUBEROYLANILIDE HYDROXAMIC ACID; T-CELL LYMPHOMA; DOWN-REGULATION; HDAC
INHIBITOR; EXPRESSION; APOPTOSIS; DEACETYLASES; TUMORS; KIT
AB Vorinostat is a small molecule inhibitor of class I and II histone deacetylase enzymes which alters the expression of target genes including the cell cycle gene p21, leading to cell cycle arrest and apoptosis.
Patients enrolled in a phase I trial were treated with vorinostat alone on day 1 and vorinostat and bortezomib in combination on day 9. Paired biopsies were obtained in eleven subjects. Blood samples were obtained on days 1 and 9 of cycle 1 prior to dosing and 2 and 6 h post-dosing in all 60 subjects. Gene expression of p21, HSP70, AKT, Nur77, ERB1, and ERB2 was evaluated in peripheral blood mononuclear cells and tissue samples. Chromatin immunoprecipitation of p21, HSP70, and Nur77 was also performed in biopsy samples.
In peripheral blood mononuclear cells, Nur77 was significantly and consistently decreased 2 h after vorinostat administration on both days 1 and 9, median ratio of gene expression relative to baseline of 0.69 with interquartile range 0.49-1.04 (p < 0.001); 0.28 (0.15-0.7) (p < 0.001), respectively, with more pronounced decrease on day 9, when patients received both vorinostat and bortezomib. p21, a downstream target of Nur77, was significantly decreased on day 9, 2 and 6 h after administration of vorinostat and bortezomib, 0.67 (0.41-1.03) (p < 0.01); 0.44 (0.25-1.3) (p < 0.01), respectively. The ChIP assay demonstrated a protein-DNA interaction, in this case interaction of Nur77, HSP70 and p21 with acetylated histone H3, at baseline and at day 9 after treatment with vorinostat in tissue biopsies in most patients.
Vorinostat inhibits Nur77 expression, which in turn may decrease p21 and AKT expression in PBMCs. The influence of vorinostat on target gene expression in tumor tissue was variable; however, most patients demonstrated interaction of acetylated H3 with Nur77, HSP70, and p21 which provides evidence of interaction with the transcriptionally active acetylated H3.
C1 [Kolesar, Jill M.; Traynor, Anne M.; Holen, Kyle D.; Hoang, Tien; Seo, Songwon; Kim, KyungMann; Alberti, Dona; Wilding, George; Bailey, Howard H.; Schelman, William R.] Univ Wisconsin, Carbone Comprehens Canc Ctr, Madison, WI 53792 USA.
[Seo, Songwon; Kim, KyungMann] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53792 USA.
[Espinoza-Delgado, Igor; Wright, John J.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Kolesar, JM (reprint author), Univ Wisconsin, Carbone Comprehens Canc Ctr, 600 Highland Ave,K4-554 CSC, Madison, WI 53792 USA.
EM jmkolesar@pharmacy.wisc.edu
FU Early Clinical Trials of Anti-Cancer Agents with Phase I Emphasis, NCI;
CTEP Translational Research Initiative [UO1 CA062491]; Clinical and
Translational Science Award, National Center for Research Resources, NIH
[1UL 1RR025011]; NIH/NCI [P30 CA014520]
FX We thank the University of Wisconsin Carbone Cancer Center (UWCCC)
Analytical Instrumentation Laboratory for Pharmacokinetics,
Pharmacodynamics, and Pharmacogenetics (3P Lab) for acquisition of gene
expression and chromatin precipitation data for this research. We also
thank the patients who participated in this clinical trial, and the
nurses and research specialist of the UWCCC Phase I Program for their
efforts in conducting and managing this trial. UO1 CA062491, Early
Clinical Trials of Anti-Cancer Agents with Phase I Emphasis, NCI; CTEP
Translational Research Initiative, Contract; and 1UL 1RR025011, Clinical
and Translational Science Award, National Center for Research Resources,
NIH. The authors would like to thank the University of Wisconsin Carbone
Cancer Center (UWCCC) for use of its Shared Services to complete this
research. This work is supported in part by NIH/NCI P30 CA014520 to the
UW Carbone Cancer Center.
NR 17
TC 2
Z9 2
U1 1
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0344-5704
J9 CANCER CHEMOTH PHARM
JI Cancer Chemother. Pharmacol.
PD SEP
PY 2013
VL 72
IS 3
BP 661
EP 667
DI 10.1007/s00280-013-2242-6
PG 7
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA 208CK
UT WOS:000323653600018
PM 23903894
ER
PT J
AU Gulley, JL
Heery, CR
Madan, RA
Walter, BA
Merino, MJ
Dahut, WL
Tsang, KY
Schlom, J
Pinto, PA
AF Gulley, James L.
Heery, Christopher R.
Madan, Ravi A.
Walter, Beatriz A.
Merino, Maria J.
Dahut, William L.
Tsang, Kwong-Yok
Schlom, Jeffrey
Pinto, Peter A.
TI Phase I study of intraprostatic vaccine administration in men with
locally recurrent or progressive prostate cancer
SO CANCER IMMUNOLOGY IMMUNOTHERAPY
LA English
DT Article
DE Cancer vaccine; Immunotherapy; PROSTVAC; Intratumoral vaccine; Prostate
cancer
ID DIVERSIFIED SUBCUTANEOUS/INTRATUMORAL VACCINATION; MULTIPLE
COSTIMULATORY MOLECULES; TUMOR-INFILTRATING LYMPHOCYTES;
COLONY-STIMULATING FACTOR; CD8(+) T-CELLS; COMBINATION THERAPY;
CUTANEOUS MELANOMA; PROGNOSTIC-FACTOR; DENDRITIC CELLS; GENE-THERAPY
AB The primary end point of this study was to determine the safety and feasibility of intraprostatic administration of PSA-TRICOM vaccine [encoding transgenes for prostate-specific antigen (PSA) and 3 costimulatory molecules] in patients with locally recurrent or progressive prostate cancer. This trial was a standard 3 + 3 dose escalation with 6 patients each in cohorts 4 and 5 to gather more immunologic data. Nineteen of 21 patients enrolled had locally recurrent prostate cancer after definitive radiation therapy, and 2 had no local therapy. All cohorts received initial subcutaneous vaccination with recombinant vaccinia (rV)-PSA-TRICOM and intraprostatic booster vaccinations with recombinant fowlpox (rF)-PSA-TRICOM. Cohorts 3-5 also received intraprostatic rF-GM-CSF. Cohort 5 received additional subcutaneous boosters with rF-PSA-TRICOM and rF-GM-CSF. Patients had pre- and post-treatment prostate biopsies, and analyses of peripheral and intraprostatic immune cells were performed. There were no dose-limiting toxicities, and the maximum tolerated dose was not reached. The most common grade 2 adverse events were fever (38 %) and subcutaneous injection site reactions (33 %); the single grade 3 toxicity was transient fever. Overall, 19 of 21 patients on trial had stable (10) or improved (9) PSA values. There was a marked increase in CD4(+) (p = 0.0002) and CD8(+) (p = 0.0002) tumor infiltrates in post- versus pre-treatment tumor biopsies. Four of 9 patients evaluated had peripheral immune responses to PSA or NGEP. Intraprostatic administration of PSA-TRICOM is safe and feasible and can generate a significant immunologic response. Improved serum PSA kinetics and intense post-vaccination inflammatory infiltrates were seen in the majority of patients. Clinical trials examining clinical end points are warranted.
C1 [Gulley, James L.; Heery, Christopher R.; Madan, Ravi A.; Tsang, Kwong-Yok; Schlom, Jeffrey] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Walter, Beatriz A.; Merino, Maria J.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Dahut, William L.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Pinto, Peter A.] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Gulley, JL (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, 10 Ctr Dr,8B09 MSC 1750, Bethesda, MD 20892 USA.
EM gulleyj@mail.nih.gov
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
FU Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health
FX Grant support was provided by the Intramural Research Program of the
Center for Cancer Research, National Cancer Institute, National
Institutes of Health. The authors thank Benedetto Farsaci and Caroline
Jochems for their helpful discussions, Diane J. Poole for her technical
assistance, and Bonnie L. Casey and Debra Weingarten for their editorial
assistance in the preparation of this manuscript.
NR 44
TC 15
Z9 15
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-7004
J9 CANCER IMMUNOL IMMUN
JI Cancer Immunol. Immunother.
PD SEP
PY 2013
VL 62
IS 9
BP 1521
EP 1531
DI 10.1007/s00262-013-1448-0
PG 11
WC Oncology; Immunology
SC Oncology; Immunology
GA 208DS
UT WOS:000323657500008
PM 23836412
ER
PT J
AU Weissman, AM
AF Weissman, Allan M.
TI Ubiquitin and Drug Discovery: Challenges and Opportunities INTRODUCTION
SO CELL BIOCHEMISTRY AND BIOPHYSICS
LA English
DT Editorial Material
C1 NCI, Lab Prot Dynam & Signaling, Ctr Canc Res, Frederick, MD 21702 USA.
RP Weissman, AM (reprint author), NCI, Lab Prot Dynam & Signaling, Ctr Canc Res, Frederick, MD 21702 USA.
EM amw@nih.gov
FU Intramural NIH HHS [ZIA BC010292-15]
NR 0
TC 0
Z9 0
U1 0
U2 3
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1085-9195
J9 CELL BIOCHEM BIOPHYS
JI Cell Biochem. Biophys.
PD SEP
PY 2013
VL 67
IS 1
SI SI
BP 1
EP 2
DI 10.1007/s12013-013-9620-x
PG 2
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 208FR
UT WOS:000323663300001
PM 23754620
ER
PT J
AU Kotlarz, A
Tukaj, S
Krzewski, K
Brycka, E
Lipinska, B
AF Kotlarz, Agnieszka
Tukaj, Stefan
Krzewski, Konrad
Brycka, Elzbieta
Lipinska, Barbara
TI Human Hsp40 proteins, DNAJA1 and DNAJA2, as potential targets of the
immune response triggered by bacterial DnaJ in rheumatoid arthritis
SO CELL STRESS & CHAPERONES
LA English
DT Article
DE Anti-Hsp40 autoantibodies; Hsp40 in rheumatoid arthritis;
Cross-reactivity of anti-Hsp40 antibodies; Anti-DNAJ monoclonal
antibodies; Molecular mimicry
ID HEAT-SHOCK-PROTEIN; T-CELL REGULATION; HUMAN HOMOLOG; INFLAMMATION;
HSP70; CHAPERONE; IMPORT; DJ2
AB Hsp40 proteins of bacterial and human origin are suspected to be involved in the pathogenesis of rheumatoid arthritis (RA). It has been shown that sera of RA patients contain increased levels of antibodies directed to bacterial and human Hsp40s. The aim of this work was to explore immunological similarities between the bacterial (DnaJ) and human (DNAJA1 and DNAJA2) Hsp40 proteins in relation to their possible involvement in the RA. Using polyclonal antibodies directed against a full-length DnaJ or its domains, against DNAJA1 and DNAJA2, as well as monoclonal anti-DnaJ antibodies, we found immunological similarities between the bacterial and human Hsp40s. Both ELISA and Western blotting showed that these similarities were not restricted to the conserved J domains but were also present in the C-terminal variable regions. We also found a positive correlation between the levels of the anti-DnaJ and anti-DNAJA1 antibodies in the sera of RA patients. This finding supports the molecular mimicry hypothesis that human Hsp40 could be the targets of antibodies originally directed against bacterial DnaJ in RA.
C1 [Kotlarz, Agnieszka; Krzewski, Konrad; Lipinska, Barbara] Univ Gdansk, Dept Biochem, PL-80308 Gdansk, Poland.
[Tukaj, Stefan] Univ Gdansk, Dept Plant Physiol & Biotechnol, PL-80308 Gdansk, Poland.
[Brycka, Elzbieta] Univ Gdansk, Dept Mol Virol, PL-80822 Gdansk, Poland.
[Brycka, Elzbieta] Med Univ Gdansk, PL-80822 Gdansk, Poland.
[Krzewski, Konrad] NIAID, NIH, Rockville, MD USA.
RP Lipinska, B (reprint author), Univ Gdansk, Dept Biochem, Wita Stwosza 59, PL-80308 Gdansk, Poland.
EM lipinska@biotech.ug.gda.pl
RI Tukaj, Stefan/G-6746-2014
FU Polish Ministry of Science and Higher Education [1610/B/P01/2008/35]
FX We would like to express our thanks to Dr. B. Szewczyk for his help with
overproducing proteins in the baculovirus system. We are very grateful
to Dr. Kazutoyo Terada for his generous gift of the pMal-c2x/hdj2 and
pVL1393/hdj3 plasmids. This work was supported by a grant from the
Polish Ministry of Science and Higher Education (no. 1610/B/P01/2008/35)
to BL.
NR 26
TC 4
Z9 4
U1 0
U2 7
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1355-8145
J9 CELL STRESS CHAPERON
JI Cell Stress Chaperones
PD SEP
PY 2013
VL 18
IS 5
BP 653
EP 659
DI 10.1007/s12192-013-0407-1
PG 7
WC Cell Biology
SC Cell Biology
GA 203GI
UT WOS:000323279300010
PM 23408083
ER
PT J
AU Dehdashti, SJ
Zheng, W
Gever, JR
Wilhelm, R
Nguyen, DT
Sittampalam, G
McKew, JC
Austin, CP
Prusiner, SB
AF Dehdashti, Seameen J.
Zheng, Wei
Gever, Joel R.
Wilhelm, Robert
Dac-Trung Nguyen
Sittampalam, Gurusingham
McKew, John C.
Austin, Christopher P.
Prusiner, Stanley B.
TI A High-Throughput Screening Assay for Determining Cellular Levels of
Total Tau Protein
SO CURRENT ALZHEIMER RESEARCH
LA English
DT Article
DE Alzheimer's disease; FRET-based assay; high-throughput screening assay;
prions; neurodegenerative diseases; tau protein
ID ALZHEIMERS-DISEASE; BRAIN-INJURY; PHOSPHORYLATION; DEGRADATION;
PROPAGATION; INHIBITORS; TAUOPATHY; MELATONIN; DEMENTIA; FTDP-17
AB The microtubule-associated protein (MAP) tau has been implicated in the pathology of numerous neurodegenerative diseases. In the past decade, the hyperphosphorylated and aggregated states of tau protein have been important targets in the drug discovery field for the potential treatment of Alzheimer's disease. Although several compounds have been reported to reduce the hyperphosphorylated state of tau or impact the stabilization of tau, their therapeutic activities are remain to be validated. Recently, reduction of total cellular tau protein has emerged as an alternate intervention point for drug development and a potential treatment of tauopathies. We have developed and optimized homogenous assays, using the AlphaLISA and HTRF assay technologies, for the quantification of total cellular tau protein levels in the SH-SY5Y neuroblastoma cell line. The signal-to-basal ratios were 375 and 5.3, and the Z' factors were 0.67 and 0.60 for the AlphaLISA and HTRF tau assays, respectively. The clear advantages of these homogeneous tau assays over conventional total tau assays, such as ELISA and Western blot, are the elimination of plate wash steps and miniaturization of the assay into 1536-well plate format for the ultra-high-throughput screening of large compound libraries.
C1 [Dehdashti, Seameen J.; Zheng, Wei; Dac-Trung Nguyen; Sittampalam, Gurusingham; McKew, John C.; Austin, Christopher P.] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Gever, Joel R.; Wilhelm, Robert; Prusiner, Stanley B.] Univ Calif San Francisco, Inst Neurodegenerat Dis, San Francisco, CA 94143 USA.
[Gever, Joel R.; Wilhelm, Robert; Prusiner, Stanley B.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
RP Zheng, W (reprint author), NIH, Natl Ctr Adv Translat Sci, 9800 Med Ctr Dr,MSC 3370, Bethesda, MD 20892 USA.
EM wzheng@mail.nih.gov
FU National Center for Advancing Translational Sciences, National
Institutes of Health; NIH [AG021601, AG031220]; Tau Consortium; Sherman
Fairchild Foundation; Rainwater Charitable Foundation
FX This work was supported by the Intramural Research Program of the
Therapeutics for Rare and Neglected Diseases, National Center for
Advancing Translational Sciences, National Institutes of Health. We
thank the compound management team in NCATS for their support. This work
was also supported by research grants from the NIH to S. B. P. (AG021601
and AG031220). Additionally, S. B. P. gratefully acknowledges the
support of the Tau Consortium, the Sherman Fairchild Foundation, and the
Rainwater Charitable Foundation.
NR 36
TC 9
Z9 9
U1 1
U2 17
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1567-2050
EI 1875-5828
J9 CURR ALZHEIMER RES
JI Curr. Alzheimer Res.
PD SEP
PY 2013
VL 10
IS 7
BP 679
EP 687
PG 9
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 211ET
UT WOS:000323888500002
PM 23905996
ER
PT J
AU Kreitman, RJ
AF Kreitman, Robert J.
TI Hairy Cell Leukemia-New Genes, New Targets
SO CURRENT HEMATOLOGIC MALIGNANCY REPORTS
LA English
DT Article
DE BL22; BRAF; CD22; Dabrafenib; HCL variant; IGHV4-34; Immunotoxin; MAPK;
Melanoma; Moxetumomab pasudotox; Purine analog; Recombinant immunotoxin;
Trametinib; V600E; Vemurafenib
ID BRAF V600E MUTATION; IMMUNOTOXIN RFB4(DSFV)-PE38 BL22; TERM-FOLLOW-UP;
ANTI-CD20 MONOCLONAL-ANTIBODY; CHRONIC LYMPHOCYTIC-LEUKEMIA;
NATIONAL-CANCER-INSTITUTE; MINIMAL RESIDUAL DISEASE; LOW-DOSE
VEMURAFENIB; PHASE-II TRIAL; RECOMBINANT IMMUNOTOXIN
AB Hairy cell leukemia (HCL), a B cell malignancy comprising 2 % of all leukemias, has become quite exciting recently with regard to the development of new targets for therapy. This review will focus on advancements made within the past 1-2 years in targeted therapy for this disease. These advances may be grouped into two very difference categories, namely targeting of CD22 with the recombinant immunotoxin moxetumomab pasudotox, and targeting of the mutated BRAF component of the MAP kinase pathway. Moxetumomab pasudotox in phase I testing was recently reported to be associated with an overall response rate of 86 % and a complete remission (CR) rate of 46 % in 28 patients with relapsed and refractory HCL. Many of the CRs are without minimal residual disease (MRD). Severe or dose limiting toxicity was not observed on this trial, but a completely reversible and largely asymptomatic form of grade 2 hemolytic uremic syndrome occurred in two patients during retreatment. This agent has commenced phase III multicenter testing to validate its phase I results. An extensive number of studies have documented the V600E mutation in nearly all HCL patients, but not in similar hematologic malignancies. The thymidine kinase inhibitor vemurafenib, which inhibits the V600E mutant of BRAF, was reported to induce a CR in multiply relapsed and refractory HCL, with nearly complete clearing of MRD. One additional partial and one additional complete remission were subsequently reported.
C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Kreitman, RJ (reprint author), NCI, Mol Biol Lab, NIH, 37-5124B,37 CONVENT DR MSC 4255, Bethesda, MD 20892 USA.
EM kreitmar@mail.nih.gov
NR 134
TC 8
Z9 8
U1 0
U2 7
PU CURRENT MEDICINE GROUP
PI PHILADELPHIA
PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA
SN 1558-8211
J9 CURR HEMATOL MALIG R
JI Curr. Hematol. Malig. Rep.
PD SEP
PY 2013
VL 8
IS 3
BP 184
EP 195
DI 10.1007/s11899-013-0167-0
PG 12
WC Oncology; Hematology
SC Oncology; Hematology
GA 209EI
UT WOS:000323736700003
PM 23892906
ER
PT J
AU Duncan, WC
Zarate, CA
AF Duncan, Wallace C., Jr.
Zarate, Carlos A., Jr.
TI Ketamine, Sleep, and Depression: Current Status and New Questions
SO CURRENT PSYCHIATRY REPORTS
LA English
DT Article
DE Ketamine; NMDAantagonist; Sleep; Major depressive disorder; MDD;
Synaptic plasticity; Slow wave sleep; Slow wave activity; SWA; AMPA;
Mood; Rapid antidepressant response; Neurotrophic factors; Brain-derived
neurotrophic factor; BDNF; Treatment-resistant depression; Bipolar
depression; Sleep disorders; Psychiatry
ID RESISTANT MAJOR DEPRESSION; ACTIVITY-DEPENDENT SECRETION;
GLYCOGEN-SYNTHASE KINASE-3; NMDA RECEPTOR BLOCKADE; D-ASPARTATE
ANTAGONIST; SLOW-WAVE SLEEP; STAR-ASTERISK-D; VAL66MET POLYMORPHISM;
NEUROTROPHIC FACTOR; LITHIUM-CARBONATE
AB Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has well-described rapid antidepressant effects in clinical studies of individuals with treatment-resistant major depressive disorder (MDD). Preclinical studies investigating the effects of ketamine on brain-derived neurotrophic factor (BDNF) and on sleep slow wave activity (SWA) support its use as a prototype for investigating the neuroplastic mechanisms presumably involved in the mechanism of rapidly acting antidepressants. This review discusses human EEG slow wave sleep parameters and plasma BDNF as central and peripheral surrogate markers of plasticity, and their use in assessing ketamine's effects. Acutely, ketamine elevates BDNF levels, as well as early night SWA and high-amplitude slow waves; each of these measures correlates with change in mood in depressed patients who respond to ketamine. The slow wave effects are limited to the first night post-infusion, suggesting that their increase is part of an early cascade of events triggering improved mood. Increased total sleep and decreased waking occur during the first and second night post infusion, suggesting that these measures are associated with the enduring treatment response observed with ketamine.
C1 [Duncan, Wallace C., Jr.; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Zarate, CA (reprint author), NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
EM zaratec@mail.nih.gov
FU Intramural NIH HHS [ZIA MH002857-08, ZIA MH002927-03]
NR 65
TC 11
Z9 12
U1 3
U2 31
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1523-3812
J9 CURR PSYCHIAT REP
JI Curr. Psychiatry Rep.
PD SEP
PY 2013
VL 15
IS 9
AR 394
DI 10.1007/s11920-013-0394-z
PG 7
WC Psychiatry
SC Psychiatry
GA 208DI
UT WOS:000323656400001
PM 23949569
ER
PT J
AU Vereb, G
Lockett, SJ
AF Vereb, Gyoergy
Lockett, Stephen J.
TI Microscopy of molecular interactions
SO CYTOMETRY PART A
LA English
DT Editorial Material
C1 [Vereb, Gyoergy] Univ Debrecen, Dept Biophys & Cell Biol, Med & Hlth Sci Ctr, Debrecen, Hungary.
[Vereb, Gyoergy] Univ Debrecen, MTA DE Cell Biol & Signaling Res Grp, Med & Hlth Sci Ctr, Debrecen, Hungary.
[Lockett, Stephen J.] SAIC Frederick Inc, Opt Microscopy & Anal Lab, Adv Technol Program, Frederick, MD USA.
[Lockett, Stephen J.] Frederick Natl Lab Canc Res, Frederick, MD USA.
RP Vereb, G (reprint author), Univ Debrecen, Dept Biophys & Cell Biol, Med & Hlth Sci Ctr, Debrecen, Hungary.
EM vereb@med.unideb.hu; locketts@mail.nih.gov
RI Vereb, Gyorgy/A-4241-2008
OI Vereb, Gyorgy/0000-0003-2157-3265
NR 0
TC 3
Z9 3
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4922
EI 1552-4930
J9 CYTOM PART A
JI Cytom. Part A
PD SEP
PY 2013
VL 83
IS 9
SI SI
BP 763
EP 764
DI 10.1002/cyto.a.22339
PG 2
WC Biochemical Research Methods; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 205YF
UT WOS:000323480200001
PM 24038840
ER
PT J
AU Renz, M
AF Renz, Malte
TI Fluorescence microscopy-A historical and technical perspective
SO CYTOMETRY PART A
LA English
DT Review
DE fluorescence microscopy; historical perspective; diffraction-limited
microscopy; super-resolution microscopy
ID STRUCTURED-ILLUMINATION MICROSCOPY; LASER-SCANNING-MICROSCOPE;
PHOTOACTIVATED LOCALIZATION MICROSCOPY; OPTICAL RECONSTRUCTION
MICROSCOPY; INTERNAL-REFLECTION FLUORESCENCE; DIGITAL IMAGING
MICROSCOPY; PHOTON-COUNTING HISTOGRAM; LOW-DENSITY-LIPOPROTEIN;
CORRELATION SPECTROSCOPY; PHOTOBLEACHING RECOVERY
AB For a little more than a century, fluorescence microscopy has been an essential source of major discoveries in cell biology. Recent developments improved both visualization and quantification by fluorescence microscopy imaging and established a methodology of fluorescence microscopy. By outlining basic principles and their historical development, I seek to provide insight into and understanding of the ever-growing tools of fluorescence microscopy. Thereby, this synopsis may help the interested researcher to choose a fluorescence microscopic method capable of addressing a specific scientific question. (c) 2013 International Society for Advancement of Cytometry
C1 [Renz, Malte] Albert Einstein Coll Med, Dept Obstet & Gynecol & Womens Hlth, Bronx, NY 10461 USA.
[Renz, Malte] Eunice Kennedy Shriver Inst Child Hlth & Human De, NIH, Bethesda, MD 20892 USA.
RP Renz, M (reprint author), Albert Einstein Coll Med, Dept Obstet & Gynecol & Womens Hlth, Bronx, NY 10461 USA.
EM mrenz@montefiore.org
NR 139
TC 7
Z9 8
U1 15
U2 96
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4922
J9 CYTOM PART A
JI Cytom. Part A
PD SEP
PY 2013
VL 83
IS 9
SI SI
BP 767
EP 779
DI 10.1002/cyto.a.22295
PG 13
WC Biochemical Research Methods; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 205YF
UT WOS:000323480200003
PM 23585290
ER
PT J
AU Fisher, L
Hessler, D
Glasgow, RE
Arean, PA
Masharani, U
Naranjo, D
Strycker, LA
AF Fisher, Lawrence
Hessler, Danielle
Glasgow, Russell E.
Arean, Patricia A.
Masharani, Umesh
Naranjo, Diana
Strycker, Lisa A.
TI REDEEM: A Pragmatic Trial to Reduce Diabetes Distress
SO DIABETES CARE
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; MANAGEMENT SUPPORT PROGRAM;
SELF-MANAGEMENT; GLYCEMIC CONTROL; DEPRESSIVE SYMPTOMS; INTERVENTION;
OUTCOMES; SCALE; RECRUITMENT; THERAPY
AB OBJECTIVE To compare three interventions to reduce diabetes distress (DD) and improve self-management among non-clinically depressed adults with type 2 diabetes mellitus (T2DM).RESEARCH DESIGN AND METHODS In REDEEM, 392 adults with T2DM and DD were randomized to computer-assisted self-management (CASM), CASM plus DD-specific problem solving (CAPS), or a computer-administered minimal supportive intervention. Primary outcomes were Diabetes Distress Scale (DDS) total, the Emotional Burden (EB) and Regimen Distress (RD) DDS subscales, and diet, exercise, and medication adherence.RESULTS Significant and clinically meaningful reductions in DD (DDS, EB, and RD) and self-management behaviors occurred in all three conditions (P < 0.001), with no significant between-group differences. There was, however, a significant group x baseline distress interaction (P < 0.02), in which patients with high baseline RD in the CAPS condition displayed significantly larger RD reductions than those in the other two conditions. RD generated the most distress and displayed the greatest distress reduction as a result of intervention. The pace of DD reduction varied by patient age: older patients demonstrated significant reductions in DD early in the intervention, whereas younger adults displayed similar reductions later. Reductions in DD were accompanied by significant improvements in healthy eating, physical activity, and medication adherence, although not by change in HbA(1c).CONCLUSIONS DD is malleable and highly responsive to intervention. Interventions that enhance self-management also reduce DD significantly, but DD-specific interventions may be necessary for patients with high initial levels of DD. Future research should identify the minimal, most cost-effective interventions to reduce DD and improve self-management.
C1 [Fisher, Lawrence; Hessler, Danielle; Arean, Patricia A.; Masharani, Umesh; Naranjo, Diana] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Glasgow, Russell E.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA.
[Strycker, Lisa A.] Oregon Res Inst, Eugene, OR 97403 USA.
RP Fisher, L (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA.
EM fisherl@fcm.ucsf.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
[DK061937]
FX This research was funded by National Institute of Diabetes and Digestive
and Kidney Diseases (NIDDK) Grant DK061937.
NR 39
TC 52
Z9 55
U1 0
U2 15
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD SEP
PY 2013
VL 36
IS 9
BP 2551
EP 2558
DI 10.2337/dc12-2493
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 205CZ
UT WOS:000323420200038
PM 23735726
ER
PT J
AU Jasuja, GK
Travison, TG
Davda, M
Rose, AJ
Zhang, AQ
Kushnir, MM
Rockwood, AL
Meikle, W
Coviello, AD
D'Agostino, R
Vasan, RS
Bhasin, S
AF Jasuja, Guneet Kaur
Travison, Thomas G.
Davda, Maithili
Rose, Adam J.
Zhang, Anqi
Kushnir, Mark M.
Rockwood, Alan L.
Meikle, Wayne
Coviello, Andrea D.
D'Agostino, Ralph
Vasan, Ramachandran S.
Bhasin, Shalender
TI Circulating Estrone Levels Are Associated Prospectively With Diabetes
Risk in Men of the Framingham Heart Study
SO DIABETES CARE
LA English
DT Article
ID HORMONE-BINDING GLOBULIN; TANDEM MASS-SPECTROMETRY; ENDOGENOUS
SEX-HORMONES; MIDDLE-AGED MEN; POSTMENOPAUSAL WOMEN; INSULIN
CONCENTRATIONS; REPLACEMENT THERAPY; GLUCOSE-TOLERANCE; GLYCEMIC
CONTROL; ESTRADIOL LEVELS
AB OBJECTIVE In postmenopausal women and preclinical murine models, estrogen administration reduces diabetes risk; however, the relationship of estradiol and estrone to diabetes in men is poorly understood. We determined the relationship between circulating estradiol and estrone levels and diabetes risk in community-dwelling men of the Framingham Heart Study (FHS).RESEARCH DESIGN AND METHODS Cross-sectional relationships of estradiol and estrone levels with diabetes were assessed at examination 7 (1998-2001) in FHS generation 2 men (n = 1,458); prospective associations between hormone levels at examination 7 and incident diabetes were assessed 6.8 years later at examination 8. Type 2 diabetes mellitus was defined as fasting glucose >125 mg/dL, medication use, or both. Estradiol, estrone, and testosterone levels were measured with liquid chromatography-tandem mass spectrometry, and free estradiol and estrone were calculated.RESULTS In cross-sectional models, men with elevated estrone and estradiol had 40% and 62% increased likelihoods of existing diabetes per cross-sectional doubling of estrone and estradiol levels, respectively. Free estrone (cross-sectional odds ratio 1.28 [95% CI 1.02-1.62], P = 0.04) was associated with impaired fasting glucose at examination 7. There was an increase in risk of existing diabetes with increasing quartiles of total and free estrone and estradiol and an increase in risk of incident diabetes with increasing quartiles of estrone levels. In multivariate longitudinal analyses, a twofold increase in total or free estrone levels at examination 7 was associated with 77 and 93% increases, respectively, in odds of incident diabetes at examination 8.CONCLUSIONS Although both estradiol and estrone exhibit cross-sectional associations with diabetes in men, in longitudinal analyses estrone is a more sensitive marker of diabetes risk than is estradiol.
C1 [Jasuja, Guneet Kaur; D'Agostino, Ralph] Boston Univ, Dept Math, Boston, MA 02215 USA.
[Jasuja, Guneet Kaur; Rose, Adam J.; D'Agostino, Ralph] Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA.
[Travison, Thomas G.; Davda, Maithili; Zhang, Anqi; Coviello, Andrea D.; Bhasin, Shalender] Boston Univ, Sch Med, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA.
[Travison, Thomas G.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Rose, Adam J.] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA.
[Kushnir, Mark M.; Rockwood, Alan L.; Meikle, Wayne] Univ Utah, ARUP Labs, Salt Lake City, UT USA.
[Coviello, Andrea D.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA.
[Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
RP Jasuja, GK (reprint author), Boston Univ, Dept Math, Boston, MA 02215 USA.
EM guneetk@bu.edu
OI Ramachandran, Vasan/0000-0001-7357-5970
FU National Institutes of Health [1RO1-AG-31206, 5R01-DK-092938]; Boston
Claude D. Pepper Older Americans Independence Center from the National
Institute on Aging [5P30-AG-031679]; Centers for Disease Control and
Prevention Foundation; National Heart, Lung, and Blood Institute's
Framingham Heart Study [N01-HC-25195]
FX This project was supported primarily by National Institutes of Health
grants 1RO1-AG-31206 and 5R01-DK-092938 to R. S. V. and S. B. Additional
support was provided by the Boston Claude D. Pepper Older Americans
Independence Center Grant 5P30-AG-031679 from the National Institute on
Aging and by a grant from the Centers for Disease Control and Prevention
Foundation. The Framingham Heart Study is supported by the National
Heart, Lung, and Blood Institute's Framingham Heart Study contract
N01-HC-25195.
NR 34
TC 8
Z9 8
U1 3
U2 6
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD SEP
PY 2013
VL 36
IS 9
BP 2591
EP 2596
DI 10.2337/dc12-2477
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 205CZ
UT WOS:000323420200044
PM 23690532
ER
PT J
AU Cheng, YLJ
Imperatore, G
Geiss, LS
Wang, J
Saydah, SH
Cowie, CC
Gregg, EW
AF Cheng, Yiling J.
Imperatore, Giuseppina
Geiss, Linda S.
Wang, Jing
Saydah, Sharon H.
Cowie, Catherine C.
Gregg, Edward W.
TI Secular Changes in the Age-Specific Prevalence of Diabetes Among US
Adults: 1988-2010
SO DIABETES CARE
LA English
DT Article
ID BODY-MASS INDEX; TO-HEIGHT RATIO; WAIST CIRCUMFERENCE; CARDIOMETABOLIC
RISK; EXPERT COMMITTEE; UNITED-STATES; TRENDS; OBESITY; POPULATION;
MORTALITY
AB OBJECTIVE To examine the age-specific changes of prevalence of diabetes among U.S. adults during the past 2 decades.RESEARCH DESIGN AND METHODS This study included 22,586 adults sampled in three periods of the National Health and Nutrition Examination Survey (1988-1994, 1999-2004, and 2005-2010). Diabetes was defined as having self-reported diagnosed diabetes or having a fasting plasma glucose level 126 mg/dL or HbA(1c) 6.5% (48 mmol/mol).RESULTS The number of adults with diabetes increased by 75% from 1988-1994 to 2005-2010. After adjusting for sex, race/ethnicity, and education level, the prevalence of diabetes increased over the two decades across all age-groups. Younger adults (20-34 years of age) had the lowest absolute increase in diabetes prevalence of 1.0%, followed by middle-aged adults (35-64) at 2.7% and older adults (65) at 10.0% (all P < 0.001). Comparing 2005-2010 with 1988-1994, the adjusted prevalence ratios (PRs) by age-group were 2.3, 1.3, and 1.5 for younger, middle-aged, and older adults, respectively (all P < 0.05). After additional adjustment for body mass index (BMI), waist-to-height ratio (WHtR), or waist circumference (WC), the adjusted PR remained statistically significant only for adults 65 years of age.CONCLUSIONS During the past two decades, the prevalence of diabetes increased across all age-groups, but adults 65 years of age experienced the largest increase in absolute change. Obesity, as measured by BMI, WHtR, or WC, was strongly associated with the increase in diabetes prevalence, especially in adults <65.
C1 [Cheng, Yiling J.; Imperatore, Giuseppina; Geiss, Linda S.; Wang, Jing; Saydah, Sharon H.; Gregg, Edward W.] Ctr Dis Control & Prevent, Div Diabet Translat, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA.
[Cowie, Catherine C.] NIDDK, NIH, Bethesda, MD USA.
RP Cheng, YLJ (reprint author), Ctr Dis Control & Prevent, Div Diabet Translat, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA.
EM ycheng@cdc.gov
NR 38
TC 74
Z9 74
U1 0
U2 9
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD SEP
PY 2013
VL 36
IS 9
BP 2690
EP 2696
DI 10.2337/dc12-2074
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 205CZ
UT WOS:000323420200058
PM 23637354
ER
PT J
AU Rosenquist, KJ
Massaro, JM
Pencina, KM
D'Agostino, RB
Beiser, A
O'Connor, GT
O'Donnell, CJ
Wolf, PA
Polak, JF
Seshadri, S
Fox, CS
AF Rosenquist, Klara J.
Massaro, Joseph M.
Pencina, Karol M.
D'Agostino, Ralph B.
Beiser, Alexa
O'Connor, George T.
O'Donnell, Christopher J.
Wolf, Philip A.
Polak, Joseph F.
Seshadri, Sudha
Fox, Caroline S.
TI Neck Circumference, Carotid Wall Intima-Media Thickness, and Incident
Stroke
SO DIABETES CARE
LA English
DT Letter
C1 [Rosenquist, Klara J.; Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol & Metab, Boston, MA 02115 USA.
[Rosenquist, Klara J.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
[Rosenquist, Klara J.; Massaro, Joseph M.; D'Agostino, Ralph B.; Beiser, Alexa; O'Connor, George T.; O'Donnell, Christopher J.; Wolf, Philip A.; Seshadri, Sudha; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Rosenquist, Klara J.; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Div Intramural Res, Framingham, MA USA.
[Rosenquist, Klara J.; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Ctr Populat Studies, Framingham, MA USA.
[Massaro, Joseph M.; Beiser, Alexa] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Pencina, Karol M.; D'Agostino, Ralph B.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[O'Connor, George T.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Beiser, Alexa; Wolf, Philip A.; Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Polak, Joseph F.] Tufts Med Ctr, Dept Radiol, Boston, MA USA.
RP Fox, CS (reprint author), Brigham & Womens Hosp, Div Endocrinol & Metab, 75 Francis St, Boston, MA 02115 USA.
EM foxca@nhlbi.nih.gov
OI Massaro, Joseph/0000-0002-2682-4812; Seshadri,
Sudha/0000-0001-6135-2622; Beiser, Alexa/0000-0001-8551-7778
FU NHLBI NIH HHS [HL081352, N01-HC-25195, N01HC25195, R01 HL069003, R01
HL081352, T32 HL007224]; NIA NIH HHS [R01 AG008122, R01 AG033193]; NINDS
NIH HHS [R01 NS017950, R01 NS17950]; PHS HHS [R01 031287, R01 033193,
R01 08122, R01 33040]
NR 5
TC 8
Z9 8
U1 0
U2 2
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD SEP
PY 2013
VL 36
IS 9
BP E153
EP E154
DI 10.2337/dc13-0379
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 205CZ
UT WOS:000323420200011
PM 23970728
ER
PT J
AU Guirguis, E
Hockman, S
Chung, YW
Ahmad, F
Gavrilova, O
Raghavachari, N
Yang, YQ
Niu, G
Chen, XY
Yu, ZX
Liu, SW
Degerman, E
Manganiello, V
AF Guirguis, Emilia
Hockman, Steven
Chung, Youn Wook
Ahmad, Faiyaz
Gavrilova, Oksana
Raghavachari, Nalini
Yang, Yanqin
Niu, Gang
Chen, Xiaoyuan
Yu, Zu Xi
Liu, Shiwei
Degerman, Eva
Manganiello, Vincent
TI A Role for Phosphodiesterase 3B in Acquisition of Brown Fat
Characteristics by White Adipose Tissue in Male Mice
SO ENDOCRINOLOGY
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; INSULIN-RESISTANCE; ADIPOCYTE DIFFERENTIATION;
ENERGY HOMEOSTASIS; PPAR-GAMMA; TRANSCRIPTIONAL COMPLEX;
MITOCHONDRIAL-FUNCTION; SKELETAL-MUSCLE; DEFICIENT MICE; OBESITY
AB Obesity is linked to various diseases, including insulin resistance, diabetes, and cardiovascular disorders. The idea of inducing white adipose tissue (WAT) to assume characteristics of brown adipose tissue (BAT), and thus gearing it to fat burning instead of storage, is receiving serious consideration as potential treatment for obesity and related disorders. Phosphodiesterase 3B (PDE3B) links insulin-and cAMP-signaling networks in tissues associated with energy metabolism, including WAT. We used C57BL/6 PDE3B knockout (KO) mice to elucidate mechanisms involved in the formation of BAT in epididymal WAT (EWAT) depots. Examination of gene expression profiles in PDE3B KO EWAT revealed increased expression of several genes that block white and promote brown adipogenesis, such as C-terminal binding protein, bone morphogenetic protein 7, and PR domain containing 16, but a clear BAT-like phenotype was not completely induced. However, acute treatment of PDE3B KO mice with the beta 3-adrenergic agonist, CL316243, markedly increased the expression of cyclooxygenase-2, which catalyzes prostaglandin synthesis and is thought to be important in the formation of BAT in WAT and the elongation of very long-chain fatty acids 3, which is linked to BAT recruitment upon cold exposure, causing a clear shift toward fat burning and the induction of BAT in KO EWAT. These data provide insight into the mechanisms of BAT formation in mouse EWAT, suggesting that, in a C57BL/6 background, an increase in cAMP, caused by ablation of PDE3B and administration of CL316243, may promote differentiation of prostaglandin-responsive progenitor cells in the EWAT stromal vascular fraction into functional brown adipocytes.
C1 [Guirguis, Emilia; Hockman, Steven; Chung, Youn Wook; Ahmad, Faiyaz; Liu, Shiwei; Manganiello, Vincent] NHLBI, Pulm Cardiovasc Branch, NIH, Bethesda, MD 20892 USA.
[Raghavachari, Nalini; Yang, Yanqin] NHLBI, Genom Core, NIH, Bethesda, MD 20892 USA.
[Gavrilova, Oksana] NIDDK, NIH, Bethesda, MD 20892 USA.
[Niu, Gang; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA.
[Yu, Zu Xi] NIH, Pathol Core, Bethesda, MD 20892 USA.
[Degerman, Eva] Lund Univ, Dept Expt Med Sci, Div Diabet Metab & Endocrinol, SE-22184 Lund, Sweden.
RP Guirguis, E (reprint author), NHLBI, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM emilia.guirguis@nih.gov; manganiv@nhlbi.nih.gov
FU National Heart, Lung, and Blood Institute; National Institute of
Diabetes and Digestive and Kidney Diseases; National Institute of
Biomedical Imaging and Bioengineering Intramural Research Programs;
Swedish Research Council [3362]
FX This work was supported by the National Heart, Lung, and Blood Institute
(to E. G., S. H., Y.W.C., F. A., N.R., Y.Y., S. L., Z.X.Y., V. M.), the
National Institute of Diabetes and Digestive and Kidney Diseases (to
O.G.), the National Institute of Biomedical Imaging and Bioengineering
Intramural Research Programs (to G.N., X. C.), and the Swedish Research
Council Project 3362 (to E. D.).
NR 77
TC 10
Z9 10
U1 0
U2 4
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD SEP
PY 2013
VL 154
IS 9
BP 3152
EP 3167
DI 10.1210/en.2012-2185
PG 16
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 207RE
UT WOS:000323620100020
PM 23766131
ER
PT J
AU Murthy, SRK
Thouennon, E
Li, WS
Cheng, Y
Bhupatkar, J
Cawley, NX
Lane, M
Merchenthaler, I
Loh, YP
AF Murthy, S. R. K.
Thouennon, E.
Li, W. -S.
Cheng, Y.
Bhupatkar, J.
Cawley, N. X.
Lane, M.
Merchenthaler, I.
Loh, Y. P.
TI Carboxypeptidase E Protects Hippocampal Neurons During Stress in Male
Mice by Up-regulating Pro-survival BCL2 Protein Expression
SO ENDOCRINOLOGY
LA English
DT Article
ID CHRONIC PSYCHOSOCIAL STRESS; CENTRAL-NERVOUS-SYSTEM; MESSENGER-RNA;
RAT-BRAIN; SPATIAL MEMORY; GLUCOCORTICOIDS; MORPHOLOGY; PRETREATMENT;
COMBINATION; ISCHEMIA
AB Prolonged chronic stress causing elevated plasma glucocorticoids leads to neurodegeneration. Adaptation to stress (allostasis) through neuroprotective mechanisms can delay this process. Studies on hippocampal neurons have identified carboxypeptidase E (CPE) as a novel neuroprotective protein that acts extracellularly, independent of its enzymatic activity, although the mechanism of action is unclear. Here, we aim to determine if CPE plays a neuroprotective role in allostasis in mouse hippocampus during chronic restraint stress (CRS), and the molecular mechanisms involved. Quantitative RT-PCR/in situ hybridization and Western blots were used to assay for mRNA and protein. After mild CRS (1 h/d for 7 d), CPE protein and mRNA were significantly elevated in the hippocampal CA3 region, compared to naive littermates. In addition, luciferase reporter assays identified a functional glucocorticoid regulatory element within the cpe promoter that mediated the up-regulation of CPE expression in primary hippocampal neurons following dexamethasone treatment, suggesting that circulating plasma glucocorticoids could evoke a similar effect on CPE in the hippocampus in vivo. Overexpression of CPE in hippocampal neurons, or CRS in mice, resulted in elevated prosurvival BCL2 protein/mRNA and p-AKT levels in the hippocampus; however, CPE-/- mice showed a decrease. Thus, during mild CRS, CPE expression is up-regulated, possibly contributed by glucocorticoids, to mediate neuroprotection of the hippocampus by enhancing BCL2 expression through AKT signaling, and thereby maintaining allostasis.
C1 [Murthy, S. R. K.; Thouennon, E.; Cheng, Y.; Bhupatkar, J.; Cawley, N. X.; Loh, Y. P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
[Li, W. -S.] Sun Yat Sen Univ, Sch Life Sci, Guangzhou 510275, Guangdong, Peoples R China.
[Lane, M.; Merchenthaler, I.] Univ Maryland, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
RP Loh, YP (reprint author), NIH, 49 Convent Dr,Bldg 49,Room 5A-22, Bethesda, MD 20892 USA.
EM lohp@mail.nih.gov
OI Cheng, Yong/0000-0002-7529-4408
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Bethesda, Maryland
FX This research was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Bethesda, Maryland.
NR 38
TC 7
Z9 7
U1 0
U2 1
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD SEP
PY 2013
VL 154
IS 9
BP 3284
EP 3293
DI 10.1210/en.2013-1118
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 207RE
UT WOS:000323620100032
PM 23825125
ER
PT J
AU Liu, JF
Tolaney, SM
Birrer, M
Fleming, GF
Buss, MK
Dahlberg, SE
Lee, H
Whalen, C
Tyburski, K
Winer, E
Ivy, P
Matulonis, UA
AF Liu, Joyce F.
Tolaney, Sara M.
Birrer, Michael
Fleming, Gini F.
Buss, Mary K.
Dahlberg, Suzanne E.
Lee, Hang
Whalen, Christin
Tyburski, Karin
Winer, Eric
Ivy, Percy
Matulonis, Ursula A.
TI A Phase 1 trial of the poly(ADP-ribose) polymerase inhibitor olaparib
(AZD2281) in combination with the anti-angiogenic cediranib (AZD2171) in
recurrent epithelial ovarian or triple-negative breast cancer
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Article
DE Olaparib; PARP-inhibitor; Cediranib; Anti-angiogenic; Ovarian; Breast;
Phase 1
ID HOMOLOGOUS RECOMBINATION; DOWN-REGULATION; SOLID TUMORS; DNA-REPAIR;
BEVACIZUMAB; HYPOXIA; RAD51; BRCA1; CELLS
AB Background: Poly(ADP-ribose) polymerase (PARP)-inhibitors and anti-angiogenics have activity in recurrent ovarian and breast cancer; however, the effect of combined therapy against PARP and angiogenesis in this population has not been reported. We investigated the toxicities and recommended phase 2 dosing (RP2D) of the combination of cediranib, a multitargeted inhibitor of vascular endothelial growth factor receptor (VEGFR)-1/2/3 and olaparib, a PARP-inhibitor (NCT01116648).
Methods: Cediranib tablets once daily and olaparib capsules twice daily were administered orally in a standard 3+3 dose escalation design. Patients with recurrent ovarian or metastatic triple-negative breast cancer were eligible. Patients had measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or met Gynecologic Cancer InterGroup (GCIG) CA125 criteria. No prior PARP-inhibitors or anti-angiogenics in the recurrent setting were allowed.
Results: 28 patients (20 ovarian, 8 breast) enrolled to 4 dose levels. 2 dose limiting toxicities (DLTs) (1 grade 4 neutropenia >= 4 days; 1 grade 4 thrombocytopenia) occurred at the highest dose level (cediranib 30 mg daily; olaparib 400 mg twice daily [BID]). The RP2D was cediranib 30 mg daily and olaparib 200 mg BID. Grade 3 or higher toxicities occurred in 75% of patients, and included grade 3 hypertension (25%) and grade 3 fatigue (18%). One grade 3 bowel obstruction occurred. The overall response rate (ORR) in the 18 RECIST-evaluable ovarian cancer patients was 44%, with a clinical benefit rate (ORR plus stable disease (SD) >24 weeks) of 61%. None of the seven evaluable breast cancer patients achieved clinical response; two patients had stable disease for >24 weeks.
Interpretation: The combination of cediranib and olaparib has haematologic DLTs and anticipated class toxicities, with promising evidence of activity in ovarian cancer patients. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Liu, Joyce F.; Tolaney, Sara M.; Whalen, Christin; Tyburski, Karin; Winer, Eric; Matulonis, Ursula A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Birrer, Michael] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA.
[Fleming, Gini F.] Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA.
[Buss, Mary K.] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA.
[Dahlberg, Suzanne E.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.
[Lee, Hang] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA.
[Ivy, Percy] NIH, Canc Therapy Evaluat Program, Bethesda, MD USA.
RP Liu, JF (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA.
EM joyce_liu@dfci.harvard.edu
FU Cancer Therapy Evaluation Program of the National Cancer Institute;
National Institutes of Health [3 U01 CA062490-16S2]
FX This study was sponsored by the Cancer Therapy Evaluation Program of the
National Cancer Institute and supported by a Grant through the National
Institutes of Health (3 U01 CA062490-16S2). The funding source had no
role in the conduct, data collection or analysis of the study.
NR 23
TC 51
Z9 59
U1 2
U2 17
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD SEP
PY 2013
VL 49
IS 14
BP 2972
EP 2978
DI 10.1016/j.ejca.2013.05.020
PG 7
WC Oncology
SC Oncology
GA 207MM
UT WOS:000323604700003
PM 23810467
ER
PT J
AU Tandle, AT
Kramp, T
Kil, WJ
Halthore, A
Gehlhaus, K
Shankavaram, U
Tofilon, PJ
Caplen, NJ
Camphausen, K
AF Tandle, Anita T.
Kramp, Tamalee
Kil, Whoon J.
Halthore, Aditya
Gehlhaus, Kristen
Shankavaram, Uma
Tofilon, Philip J.
Caplen, Natasha J.
Camphausen, Kevin
TI Inhibition of polo-like kinase 1 in glioblastoma multiforme induces
mitotic catastrophe and enhances radiosensitisation
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Article
DE Glioblastoma multiforme; PLK1; GSK461364A; siRNA; Radiation
ID DNA-DAMAGE CHECKPOINT; ADJUVANT TEMOZOLOMIDE; THERAPEUTIC TARGET;
CANCER-THERAPY; CELL-LINES; RNAI; RADIOTHERAPY; GROWTH; BRAIN; PLK1
AB Glioblastoma multiforme (GBM) is the most common primary brain tumour in the United States of America (USA) with a median survival of approximately 14 months. Low survival rates are attributable to the aggressiveness of GBM and a lack of understanding of the molecular mechanisms underlying GBM. The disruption of signalling pathways regulated either directly or indirectly by protein kinases is frequently observed in cancer cells and thus the development of inhibitors of specific kinases has become a major focus of drug discovery in oncology. To identify protein kinases required for the survival of GBM we performed a siRNA-based RNAi screen focused on the human kinome in GBM. Inhibition of the polo-like kinase 1 (PLK1) induced a reduction in the viability in two different GBM cell lines. To assess the potential of inhibiting PLK1 as a treatment strategy for GBM we examined the effects of a small molecule inhibitor of PLK1, GSK461364A, on the growth of GBM cells. PLK1 inhibition arrested cells in the mitotic phase of the cell cycle and induced cell kill by mitotic catastrophe. GBM engrafts treated with GSK461364A showed statistically significant inhibition of tumour growth. Further, exposure of different GBM cells to RNAi or GSK461364A prior to radiation resulted in an increase in their radiosensitivity with dose enhancement factor ranging from 1.40 to 1.53 with no effect on normal cells. As a measure of DNA double strand breaks, gamma H2AX levels were significantly higher in the combined modality as compared to the individual treatments. This study suggests that PLK1 is an important therapeutic target for GBM and can enhance radiosensitivity in GBM. Published by Elsevier Ltd.
C1 [Tandle, Anita T.; Kramp, Tamalee; Kil, Whoon J.; Halthore, Aditya; Shankavaram, Uma; Tofilon, Philip J.; Camphausen, Kevin] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Gehlhaus, Kristen; Caplen, Natasha J.] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Camphausen, K (reprint author), NCI, Radiat Oncol Branch, 10 Ctr Dr B2-3561, Bethesda, MD 20892 USA.
EM camphauk@mail.nih.gov
RI Caplen, Natasha/H-2768-2016
OI Caplen, Natasha/0000-0002-0001-9460
FU National Institutes of Health, National Cancer Institute
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute.
NR 37
TC 21
Z9 22
U1 0
U2 14
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD SEP
PY 2013
VL 49
IS 14
BP 3020
EP 3028
DI 10.1016/j.ejca.2013.05.013
PG 9
WC Oncology
SC Oncology
GA 207MM
UT WOS:000323604700009
PM 23790466
ER
PT J
AU Morris, CP
Torrero, MN
Larson, D
Evans, H
Shi, YH
Cox, RT
Mitre, E
AF Morris, C. Paul
Torrero, Marina N.
Larson, David
Evans, Holly
Shi, Yinghui
Cox, Rachel T.
Mitre, Edward
TI Vaccination with intestinal tract antigens does not induce protective
immunity in a permissive model of filariasis
SO EXPERIMENTAL PARASITOLOGY
LA English
DT Article
DE Filaria; Litomosoides sigmodontis; Vaccine; Hidden; Antigen; Intestine;
Helminth
ID ASPARAGINYL ENDOPEPTIDASE SM32; CHRONIC LYMPHATIC FILARIASIS; JIRDS
MERIONES-UNGUICULATUS; H-GAL-GP; HAEMONCHUS-CONTORTUS;
LITOMOSOIDES-SIGMODONTIS; BRUGIA-MALAYI; DIROFILARIA-IMMITIS; HOOKWORM
INFECTION; NEUTRALIZING ANTIBODIES
AB Antigens obtained from the intestinal tract of filarial nematodes have been proposed as potential safe and effective vaccine candidates. Because they may be 'hidden' from the immune response during natural infection, yet accessible by antibodies induced by vaccination, intestinal antigens may have a low potential for eliciting allergic responses when vaccinating previously infected individuals. Despite prior promising data, vaccination with intestinal antigens has yet to be tested in a permissive model of filariasis. In this study we investigated the efficacy of vaccination with filarial intestinal antigens in the permissive Litomosoides sigmodontis BALB/c model of filariasis, and we evaluated the extent to which these antigens are recognized by the immune system during and after infection. Infected BALB/c mice developed lower IgG antibody responses to soluble intestinal antigens (GutAg) than to soluble antigens of whole worms (LsAg). Similarly, GutAg induced less proliferation and less production of IL-4 and IFN gamma from splenocytes of infected mice than LsAg. In contrast to these differences, active infection resulted in equivalent levels of circulating GutAg-specific IgE and LsAg-specific IgE levels. Consistent with this, basophil activation, as assessed by flow cytometric staining of intracellular basophil IL-4 expression, was equivalent in response to GutAg and LsAg. Vaccination with GutAg adsorbed to CpG/alum induced GutAg specific IgG1 and IgG2A production, with GutAg specific IgG titers greater than 5-fold higher than those measured in previously infected animals. Despite this response to GutAg vaccination, vaccinated mice harbored similar parasite burdens 8 weeks post infection when compared to non-vaccinated controls. These studies demonstrate that soluble antigens obtained from the intestinal tracts of L. sigmodontis have some qualities of 'hidden' antigens, but they still sensitize mice to allergic reactions and fail to protect against future infection when given as a vaccine adsorbed to alum/CPG. Published by Elsevier Inc.
C1 [Morris, C. Paul; Torrero, Marina N.; Larson, David; Evans, Holly; Shi, Yinghui; Mitre, Edward] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Microbiol & Immunol, Bethesda, MD 20852 USA.
[Cox, Rachel T.] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Biochem, Bethesda, MD 20852 USA.
[Morris, C. Paul] NIAID, NIH, Bethesda, MD 20892 USA.
RP Mitre, E (reprint author), Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Microbiol & Immunol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM edward.mitre@usuhs.edu
OI Morris, Christopher/0000-0002-5989-3638
FU Uniformed Services University of the Health Sciences [R073UE]
FX We thank Karen Wolcott and Kateryna Lund at the Uniformed Services
University Biomedical Instrumentation Center for support with Flow
Cytometry. This work was supported by the Uniformed Services University
of the Health Sciences grant number R073UE.
NR 45
TC 2
Z9 2
U1 0
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4894
J9 EXP PARASITOL
JI Exp. Parasitol.
PD SEP
PY 2013
VL 135
IS 1
BP 87
EP 95
DI 10.1016/j.exppara.2013.05.018
PG 9
WC Parasitology
SC Parasitology
GA 207UD
UT WOS:000323629200013
PM 23792131
ER
PT J
AU Simeonov, A
AF Simeonov, Anton
TI Recent developments in the use of differential scanning fluorometry in
protein and small molecule discovery and characterization
SO EXPERT OPINION ON DRUG DISCOVERY
LA English
DT Review
DE chemical chaperones; differential scanning fluorometry; fluorescence
thermal shift; inhibitor mechanism of action; pharmacological
chaperones; thermal stabilization
ID THERMAL SHIFT ASSAYS; DRUG DISCOVERY; MONOCLONAL-ANTIBODY;
LIGAND-BINDING; STABILITY; IDENTIFICATION; FLUORESCENCE; AFFINITY;
INHIBITORS; THERMODYNAMICS
AB Introduction: Despite tremendous advances in the application of biophysical methods in drug discovery, the preponderance of instruments and techniques still require sophisticated analyses by dedicated personnel and/or large amounts of frequently hard-to-produce proteins. A technique which carries the promise of simplicity and relatively low protein consumption is the differential scanning fluorometry (DSF). This technique monitors protein through the use of environmentally sensitive fluorescent dye, in a temperature-ramp regime by observing the gradual exposure to the solvent of otherwise buried hydrophobic faces of protein domains.
Areas covered: This review describes recent developments in the field of DSF. This article pays a particular emphasis on the advances published during the 2010 - 2013 period.
Expert opinion: There has been a significant diversification of DSF applications beyond initial small molecule discovery into areas such as protein therapeutic development, formulation studies and various mechanistic investigations. This serves as a further indication of the broad penetration of the technique. In the small molecule arena, DSF has expanded toward sophisticated co-dependency MOA tests, demonstrating the wealth of information which the technique can provide. Importantly, the first public deposition of a large screening dataset may enable the use of thermal stabilization data in refining in silico models for small molecule binding.
C1 NIH, Natl Ctr Adv Translat Sci, Div Discovery Innovat, Bethesda, MD 20892 USA.
RP Simeonov, A (reprint author), NIH, Natl Ctr Adv Translat Sci, Div Discovery Innovat, 9800 Med Ctr Dr, Bethesda, MD 20892 USA.
EM asimeono@mail.nih.gov
FU US National Institutes of Health
FX A Simeonov is supported by the US National Institutes of Health.
NR 70
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Z9 10
U1 5
U2 52
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1746-0441
J9 EXPERT OPIN DRUG DIS
JI Expert. Opin. Drug Discov.
PD SEP
PY 2013
VL 8
IS 9
BP 1071
EP 1082
DI 10.1517/17460441.2013.806479
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 206FA
UT WOS:000323502200003
PM 23738712
ER
PT J
AU Kim, KH
Dmitriev, IP
Saddekni, S
Kashentseva, EA
Harris, RD
Aurigemma, R
Bae, S
Singh, KP
Siegal, GP
Curiel, DT
Alvarez, RD
AF Kim, Kenneth H.
Dmitriev, Igor P.
Saddekni, Souheil
Kashentseva, Elena A.
Harris, Raymond D.
Aurigemma, Rosemarie
Bae, Sejong
Singh, Karan P.
Siegal, Gene P.
Curiel, David T.
Alvarez, Ronald D.
TI A phase I clinical trial of Ad5/3-Delta 24, a novel serotype-chimeric,
infectivity-enhanced, conditionally-replicative adenovirus (CRAd), in
patients with recurrent ovarian cancer
SO GYNECOLOGIC ONCOLOGY
LA English
DT Article
DE CRAd; Gene therapy; Infectivity-enhanced adenoviral vectors; Ovarian
cancer
ID ONCOLYTIC ADENOVIRUS; GENE-TRANSFER; THERAPEUTIC-EFFICACY; STAGE-III;
PACLITAXEL; CISPLATIN; RECEPTOR; TROPISM; DISEASES; ONYX-015
AB Objective. The conditionally replicative adenovirus Ad5/3-Delta 24 has a type-3 knob incorporated into the type-5 fiber that facilitates enhanced ovarian cancer infectivity. Preclinical studies have shown that Ad5/3-Delta 24 achieves significant oncolysis and anti-tumor activity in ovarian cancer models. The purpose of this study was to evaluate in a phase I trial the feasibility and safety of intraperitoneal (IP) Ad5/3-Delta 24 in recurrent ovarian cancer patients.
Methods. Eligible patients were treated with IP Ad5/3-Delta 24 for 3 consecutive days in one of three dose cohorts ranging 1 x 10(10)-1 x 10(12) vp. Toxicity was assessed utilizing CfC grading and efficacy with RECIST. Ascites, serum, and other samples were obtained to evaluate gene transfer, generation of wildtype virus, viral shedding, and antibody response.
Results. Nine of 10 patients completed treatment per protocol. A total of 15 vector-related adverse events were experienced in 5 patients. These events included fever or chills, nausea, fatigue, and myalgia. All were grades 1-2 in nature, transient, and medically managed. Of the 8 treated patients evaluable for response, six patients had stable disease and 2 patients had progressive disease. Three patients had decreased, FA-125 from pretreatment levels one month after treatment Ancillary biologic studies indicated Ad5/3-Delta 24 replication in patients in the higher dose cohorts. All patients experienced an anti-adenoviral neutralizing antibody, effect.
Conclusions. This study suggests the feasibility and safety of a serotype chimeric infectivity-enhanced CRAd, Ad5/3-Delta 24, as a potential therapeutic option for recurrent ovarian cancer patients. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Kim, Kenneth H.] Univ N Carolina, Div Gynecol Oncol, Chapel Hill, NC 27515 USA.
[Dmitriev, Igor P.; Kashentseva, Elena A.; Curiel, David T.] Washington Univ, Sch Med, Div Canc Biol, St Louis, MO 63130 USA.
[Saddekni, Souheil] Univ Alabama Birmingham, Dept Radiol, Birmingham, AL 35249 USA.
[Harris, Raymond D.] NIAID, Off Biodef Res Affairs, DMID, NIH, Bethesda, MD USA.
[Aurigemma, Rosemarie] NCI, Biol Resources Branch, Bethesda, MD 20892 USA.
[Bae, Sejong; Singh, Karan P.] Univ Alabama Birmingham, Biostat & Informat Shared Facil BBSF, Birmingham, AL 35249 USA.
[Siegal, Gene P.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35249 USA.
[Alvarez, Ronald D.] Univ Alabama Birmingham, Div Gynecol Oncol, Birmingham, AL 35249 USA.
RP Alvarez, RD (reprint author), Univ Alabama Birmingham, Div Gynecol Oncol, 176F Rm 10250,619 19th St South, Birmingham, AL 35249 USA.
EM rdalvarez@uab.edu
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; UAB Comprehensive Cancer Center's Clinical Protocol
and Data Management Shared Facility [P30 CA013148]
FX Financial support: This project has been funded in whole or in part with
funds from the National Cancer Institute, National Institutes of Health,
under Contract No. HHSN261200800001E. The content of this publication
does not necessarily reflect the views of polities of the Department of
Health and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
This research was also supported by the UAB Comprehensive Cancer
Center's Clinical Protocol and Data Management Shared Facility (P30
CA013148).
NR 31
TC 25
Z9 26
U1 2
U2 10
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD SEP
PY 2013
VL 130
IS 3
BP 518
EP 524
DI 10.1016/j.ygyno.2013.06.003
PG 7
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 208OB
UT WOS:000323687900023
PM 23756180
ER
PT J
AU Luhn, P
Houldsworth, J
Cahill, L
Schiffman, M
Castle, PE
Zuna, RE
Dunn, ST
Gold, MA
Walker, J
Wentzensen, N
AF Luhn, Patricia
Houldsworth, Jane
Cahill, Lynnette
Schiffman, Mark
Castle, Philip E.
Zuna, Rosemary E.
Dunn, S. Terence
Gold, Michael A.
Walker, Joan
Wentzensen, Nicolas
TI Chromosomal gains measured in cytology samples from women with abnormal
cervical cancer screening results
SO GYNECOLOGIC ONCOLOGY
LA English
DT Article
DE Cervical cancer; Genomic gains; 3q26; FISH; HPV
ID TELOMERASE GENE TERC; GENOMIC AMPLIFICATION; CENTROSOME DUPLICATION;
UTERINE CERVIX; COPY NUMBER; PAP-SMEARS; CELL-LINES; HPV TYPE; IN-SITU;
CARCINOMA
AB Objective. Chromosomal gains at 3q26, 5p15 and 20q13 have been described in cervical precancer and cancer. We evaluated a novel fluorescence in situ hybridization (FISH) assay that detects gains at these three loci simultaneously as a possible biomarker for detecting cervical precancer.
Methods. Chromosomal copy numbers at 3q26, 5p15, 20q13 and the centromere of chromosome7 (cen7) in liquid-based cytology specimens from 168 women enrolled in the Biopsy Study were determined by FISH. The number of cells with >= 3 or >= 4 signals for a genomic locus was enumerated and diagnostic test performance measures were calculated using receiver operating characteristic (ROC) analyses. Sensitivity and specificity values were determined for the detection of CIN2 + and/or HSIL.
Results. The median number of cells with >= 3 signals increased with the severity of cervical lesion for each genomic locus (p-trend < 0.02 for each locus). ROC analysis for the number of cells with >= 3 signals resulted in area under the curve values of 0.70 (95% CI: 0.54-0.86), 0.67 (0.52-0.83), 0.67 (0.51-0.83) and 0.78 (0.64-0.92) for 3q26, 5p15, 20q13 and cen7, respectively, for the detection of CIN2 + and/or HSIL. Positivity for gains at multiple loci resulted in only slightly better test performance measures than those for the individual probes for four distinct combinations of probes.
Conclusions. Chromosomal gains at 3q26, 5p15, 20q13 and cen7 are associated with severity of cervical lesions. Further studies are required to quantify risk stratification of FISH assays for cervical cancer screening. Published by Elsevier Inc.
C1 [Luhn, Patricia; Schiffman, Mark; Wentzensen, Nicolas] NCI, Div Epidemiol & Genet, Rockville, MD USA.
[Luhn, Patricia] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, Rockville, MD USA.
[Houldsworth, Jane; Cahill, Lynnette] Canc Genet Inc, Rutherford, NJ USA.
[Castle, Philip E.] Albert Einstein Coll Med, New York, NY USA.
[Zuna, Rosemary E.; Dunn, S. Terence] Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA.
[Gold, Michael A.] Univ Oklahoma, Sch Community Med, Tulsa Canc Inst, Dept Obstet & Gynecol, Tulsa, OK USA.
[Walker, Joan] Univ Oklahoma, Hlth Sci Ctr, Dept Obstet & Gynecol, Oklahoma City, OK 73190 USA.
RP Luhn, P (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM luhnpa@mail.nih.gov
FU National Institutes of Health [R44CA139667]
FX This research was funded, in part, by the National Institutes of Health
(R44CA139667) (JH).
NR 31
TC 11
Z9 11
U1 0
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD SEP
PY 2013
VL 130
IS 3
BP 595
EP 600
DI 10.1016/j.ygyno.2013.06.005
PG 6
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 208OB
UT WOS:000323687900035
PM 23769811
ER
PT J
AU Bundorf, MK
Mata, R
Schoenbaum, M
Bhattacharya, J
AF Bundorf, M. Kate
Mata, Rui
Schoenbaum, Michael
Bhattacharya, Jay
TI Are Prescription Drug Insurance Choices Consistent With Expected Utility
Theory?
SO HEALTH PSYCHOLOGY
LA English
DT Article
DE expected utility maximization; prospect theory; Medicare Part D; risk;
information
ID MEDICARE PART-D; DECISION-MAKING; RISK AVOIDANCE; PLAN CHOICE;
HEALTH-RISK; GRAPHS; METAANALYSIS; DISPLAYS; BEHAVIOR; SCALE
AB Objective: To determine the extent to which people make choices inconsistent with expected utility theory when choosing among prescription drug insurance plans and whether tabular or graphical presentation format influences the consistency of their choices. Method: Members of an Internet-enabled panel chose between two Medicare prescription drug plans. The "low variance" plan required higher out-of-pocket payments for the drugs respondents usually took but lower out-of-pocket payments for the drugs they might need if they developed a new health condition than the "high variance" plan. The probability of a change in health varied within subjects and the presentation format (text vs. graphical) and the affective salience of the clinical condition (abstract vs. risk related to specific clinical condition) varied between subjects. Respondents were classified based on whether they consistently chose either the low or high variance plan. Logistic regression models were estimated to examine the relationship between decision outcomes and task characteristics. Results: The majority of respondents consistently chose either the low or high variance plan, consistent with expected utility theory. Half of respondents consistently chose the low variance plan. Respondents were less likely to make discrepant choices when information was presented in graphical format. Conclusions: Many people, although not all, make choices consistent with expected utility theory when they have information on differences among plans in the variance of out-of-pocket spending. Medicare beneficiaries would benefit from information on the extent to which prescription drug plans provide risk protection.
C1 [Bundorf, M. Kate] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
[Mata, Rui] Univ Basel, Dept Psychol, Basel, Switzerland.
[Schoenbaum, Michael] NIMH, Bethesda, MD 20892 USA.
[Bhattacharya, Jay] Stanford Univ, Sch Med, Ctr Primary Care & Outcomes Res, Stanford, CA 94305 USA.
RP Bundorf, MK (reprint author), Stanford Univ, Sch Med, HRP Redwood Bldg,259 Campus Dr, Stanford, CA 94305 USA.
EM bundorf@stanford.edu
RI Mata, Rui/K-8138-2015
OI Mata, Rui/0000-0002-1679-906X
FU Stanford Center on Longevity
FX This research was supported in part by the Stanford Center on Longevity.
The views expressed in this article do not necessarily reflect the
opinions of the National Institutes of Health, the Department of Health
and Human Services, or the federal government.
NR 31
TC 3
Z9 3
U1 5
U2 14
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0278-6133
J9 HEALTH PSYCHOL
JI Health Psychol.
PD SEP
PY 2013
VL 32
IS 9
SI SI
BP 986
EP 994
DI 10.1037/a0033517
PG 9
WC Psychology, Clinical; Psychology
SC Psychology
GA 209ZO
UT WOS:000323799300008
PM 24001249
ER
PT J
AU Gubin, M
Techasintana, P
Chen, J
Calaluce, R
Magee, J
Martindale, J
Gorospe, M
Casolaro, V
Stellato, C
Atasoy, U
AF Gubin, Matt
Techasintana, Pat
Chen, Jing
Calaluce, Robert
Magee, Joe
Martindale, Jennifer
Gorospe, Myriam
Casolaro, Vincenzo
Stellato, Christiana
Atasoy, Ulus
TI RNA-BINDING PROTEIN HUR COORDINATELY REGULATES GATA-3, CD4+TH2 AND TH17
CYTOKINE GENE EXPRESSION IN DOSE-DEPENDENT MANNER
SO INTERNAL MEDICINE JOURNAL
LA English
DT Meeting Abstract
C1 [Gubin, Matt; Techasintana, Pat; Chen, Jing; Calaluce, Robert; Magee, Joe; Atasoy, Ulus] Univ Missouri, Columbia, MO USA.
[Martindale, Jennifer; Gorospe, Myriam] NIA, NIH, Baltimore, MD 21224 USA.
[Casolaro, Vincenzo; Stellato, Christiana] Johns Hopkins Univ, Baltimore, MD USA.
RI Casolaro, Vincenzo/E-9144-2010; Stellato, Cristiana/P-3001-2015
OI Casolaro, Vincenzo/0000-0001-9810-0488; Stellato,
Cristiana/0000-0002-1294-8355
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 1444-0903
J9 INTERN MED J
JI Intern. Med. J.
PD SEP
PY 2013
VL 43
SU 4
SI SI
BP 2
EP 2
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 208NG
UT WOS:000323685200006
ER
PT J
AU Junttila, IS
Watson, C
Kummola, L
Chen, X
Hu-Li, J
Guo, LY
Yagi, R
Paul, WE
AF Junttila, Ilkka S.
Watson, Cynthia
Kummola, Laura
Chen, Xi
Hu-Li, Jane
Guo, Liying
Yagi, Ryoji
Paul, William E.
TI Efficient cytokine-induced IL-13 production by mast cells requires both
IL-33 and IL-3
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Mast cells; basophils; allergic inflammation; cytokines; signal
transducer and activator of transcription 5; tyrosine phosphorylation;
BAC transgenic mouse; DsRed fluorochrome
ID EXPRESSION; LIPOPOLYSACCHARIDE
AB Background: IL-13 is a critical effector cytokine for allergic inflammation. It is produced by several cell types, including mast cells, basophils, and T(H)2 cells. In mast cells and basophils its induction can be stimulated by cross-linkage of immunoglobulin receptors or cytokines. The IL-1 family members IL-33 and IL-18 have been linked to induction of IL-13 production by mast cells and basophils. In CD4 T(H)2 cells IL-33-mediated production of IL-13 requires simultaneous signal transducer and activator of transcription (STAT) 5 activation.
Objective: Here we have addressed whether cytokine-induced IL-13 production in mast cells and basophils follows the same logic as in T(H)2 cells: requirement of 2 separate signals.
Methods: By generating a bacterial artificial chromosome (BAC) transgenic IL-13 reporter mouse, we measured IL-13 production in mast cells and basophils.
Results: In mast cells harvested from peritoneal cavities, 2 cytokine signals are required for IL-13 production: IL-33 and IL-3. In bone marrow mast cells IL-13 production requires IL-33, but the requirement for a STAT5 inducer is difficult to evaluate because these cells require the continuous presence of IL-3 (a STAT5 activator) for survival. Poorer STAT5 inducers in culture (IL-4 or stem cell factor) result in less IL-13 production on IL-33 challenge, but the addition of exogenous IL-3 enhances IL-13 production. This implies that bone marrow-derived mast cells, like peritoneal mast cells and T(H)2 cells, require stimulation both by an IL-1 family member and a STAT5 inducer to secrete IL-13. Basophils follow the same rule; splenic basophils produce IL-13 in response to IL-18 or IL-33 plus IL-3.
Conclusion: Optimal IL-13 production from mast cells and basophils requires 2 cytokine signals.
C1 [Junttila, Ilkka S.; Watson, Cynthia; Chen, Xi; Hu-Li, Jane; Guo, Liying; Yagi, Ryoji; Paul, William E.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Junttila, Ilkka S.; Kummola, Laura] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland.
[Junttila, Ilkka S.] Pirkanmaa Hosp Dist, Fimlab Labs, Tampere, Finland.
RP Junttila, IS (reprint author), Biokatu 4,Rm C-306, Tampere 33520, Finland.
EM ilkka.junttila@uta.fi; wpaul@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases Intramural
Program; Finnish Medical Foundation; Competitive Research Funding of the
Tampere University Hospital [9N018]; Sigrid Juselius Foundation; Fimlab
laboratories [X51409]; Competitive Research Funding of Tampere
University Hospital; Fimlab Laboratories; Sigrig Juselius Foundation
FX Supported by the National Institute of Allergy and Infectious Diseases
Intramural Program (to I.S.J., C.W., X.C., J.H.-L., L.G., R.Y., and
W.E.P.), the Finnish Medical Foundation (to I.S.J.), Competitive
Research Funding of the Tampere University Hospital (grant 9N018, to
I.S.J.), the Sigrid Juselius Foundation (to I.S.J. and L.K.), and Fimlab
laboratories (grant X51409, to I.S.J.).; I. S. Junttila has been
supported by one or more grants from Competitive Research Funding of
Tampere University Hospital, Fimlab Laboratories, and the Sigrid
Juselius Foundation. L. Kummola has been supported by one or more grants
from the Sigrig Juselius Foundation. The rest of the authors declare
that they have no relevant conflicts of interest.
NR 22
TC 21
Z9 22
U1 0
U2 6
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD SEP
PY 2013
VL 132
IS 3
BP 704
EP +
DI 10.1016/j.jaci.2013.03.033
PG 19
WC Allergy; Immunology
SC Allergy; Immunology
GA 207OS
UT WOS:000323612000023
PM 23683462
ER
PT J
AU van der Schot, G
Zhang, ZY
Vernon, R
Shen, Y
Vranken, WF
Baker, D
Bonvin, AMJJ
Lange, OF
AF van der Schot, Gijs
Zhang, Zaiyong
Vernon, Robert
Shen, Yang
Vranken, Wim F.
Baker, David
Bonvin, Alexandre M. J. J.
Lange, Oliver F.
TI Improving 3D structure prediction from chemical shift data
SO JOURNAL OF BIOMOLECULAR NMR
LA English
DT Article
DE Nuclear magnetic resonance; Protein structure calculation; CS-ROSETTA;
Sparse data
ID PROTEIN-STRUCTURE DETERMINATION; NMR STRUCTURE DETERMINATION; STRUCTURE
GENERATION; ROSETTA; PLUS
AB We report advances in the calculation of protein structures from chemical shift nuclear magnetic resonance data alone. Our previously developed method, CS-Rosetta, assembles structures from a library of short protein fragments picked from a large library of protein structures using chemical shifts and sequence information. Here we demonstrate that combination of a new and improved fragment picker and the iterative sampling algorithm RASREC yield significant improvements in convergence and accuracy. Moreover, we introduce improved criteria for assessing the accuracy of the models produced by the method. The method was tested on 39 proteins in the 50-100 residue size range and yields reliable structures in 70 % of the cases. All structures that passed the reliability filter were accurate (< 2 RMSD from the reference).
C1 [van der Schot, Gijs; Bonvin, Alexandre M. J. J.] Univ Utrecht, Bijvoet Ctr Biomol Res, Fac Sci Chem, NL-3584 CH Utrecht, Netherlands.
[Zhang, Zaiyong; Lange, Oliver F.] Tech Univ Munich, Biomol NMR, D-85747 Garching, Germany.
[Zhang, Zaiyong; Lange, Oliver F.] Tech Univ Munich, Dept Chem, Munich Ctr Integrated Prot Sci, D-85747 Garching, Germany.
[Vernon, Robert; Baker, David] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
[Shen, Yang] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Vranken, Wim F.] VIB, Dept Biol Struct, B-1050 Brussels, Belgium.
[Vranken, Wim F.] Vrije Univ Brussel, Struct Biol Brussels, B-1050 Brussels, Belgium.
[Baker, David] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
[Lange, Oliver F.] Helmholtz Zentrum Munchen, Inst Biol Struct, D-85764 Neuherberg, Germany.
RP Bonvin, AMJJ (reprint author), Univ Utrecht, Bijvoet Ctr Biomol Res, Fac Sci Chem, Padualaan 8, NL-3584 CH Utrecht, Netherlands.
EM a.m.j.j.bonvin@uu.nl; oliver.lange@tum.de
RI Bonvin, Alexandre/A-5420-2009; Shen, Yang/C-3064-2008; Baker,
David/K-8941-2012; Vranken, Wim/J-5051-2016
OI Bonvin, Alexandre/0000-0001-7369-1322; Shen, Yang/0000-0003-1408-8034;
Baker, David/0000-0001-7896-6217; Vranken, Wim/0000-0001-7470-4324
FU German Science Foundation (DFG) [LA 1817/3-1]; Brussels Institute for
Research and Innovation (Innoviris) [BB2B 2010-1-12]; NIDDK; European
Grid Initiative (EGI) through the national GRID Initiative of Belgium
[261572]; European Grid Initiative (EGI) through the national GRID
Initiative of France; European Grid Initiative (EGI) through the
national GRID Initiative of Italy; European Grid Initiative (EGI)
through the national GRID Initiative of Germany; European Grid
Initiative (EGI) through the national GRID Initiative of Netherlands
(via the Dutch BiG Grid project); European Grid Initiative (EGI) through
the national GRID Initiative of Portugal; European Grid Initiative (EGI)
through the national GRID Initiative of Spain; European Grid Initiative
(EGI) through the national GRID Initiative of UK; European Grid
Initiative (EGI) through the national GRID Initiative of South Africa;
European Grid Initiative (EGI) through the national GRID Initiative of
Malaysia; European Grid Initiative (EGI) through the national GRID
Initiative of Taiwan
FX This work was supported by the German Science Foundation (DFG) Grant LA
1817/3-1 (to Z. Z. and O. F. L.), the Brussels Institute for Research
and Innovation (Innoviris) grant BB2B 2010-1-12 (to W. F. V.), and the
Intramural Research Program of the NIDDK (to Y. S.). The WeNMR project
(European FP7 e-Infrastructure Grant, Contract No. 261572,
www.wenmr.eu), supported by the European Grid Initiative (EGI) through
the national GRID Initiatives of Belgium, France, Italy, Germany, the
Netherlands (via the Dutch BiG Grid project), Portugal, Spain, UK, South
Africa, Malaysia, Taiwan and the Latin America GRID infrastructure via
the Gisela project is acknowledged for the use of web portals, computing
and storage facilities.
NR 22
TC 15
Z9 15
U1 1
U2 24
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0925-2738
J9 J BIOMOL NMR
JI J. Biomol. NMR
PD SEP
PY 2013
VL 57
IS 1
BP 27
EP 35
DI 10.1007/s10858-013-9762-6
PG 9
WC Biochemistry & Molecular Biology; Spectroscopy
SC Biochemistry & Molecular Biology; Spectroscopy
GA 208JH
UT WOS:000323673800004
PM 23912841
ER
PT J
AU Jean-Pierre, P
Winters, PC
Clark, JA
Warren-Mears, V
Wells, KJ
Post, DM
LaVerda, N
Van Duyn, MA
Fiscella, K
AF Jean-Pierre, Pascal
Winters, Paul C.
Clark, Jack A.
Warren-Mears, Victoria
Wells, Kristen J.
Post, Douglas M.
LaVerda, Nancy
Van Duyn, Mary Ann
Fiscella, Kevin
CA Patient Nav Res Program Grp
TI Do Better-Rated Navigators Improve Patient Satisfaction with
Cancer-Related Care?
SO JOURNAL OF CANCER EDUCATION
LA English
DT Article
DE Patient navigation; Cancer disparities; Patient Satisfaction with
Interpersonal Relationship with Navigators; Patient Satisfaction with
Cancer-Related Care
ID HEALTH DISPARITIES; RESEARCH-PROGRAM
AB Patient navigation has emerged as a promising strategy for addressing racial-ethnic and socioeconomic disparities in cancer-related care. However, little is known about the impact of patients' perception of the quality of navigation on patient outcomes. We examined the impact of better-rated navigators on patients' satisfaction with cancer-related care. The sample included 1,593 adults (85.8 % with abnormal cancer screening and 14.2 % with confirmed cancer diagnosis) who received patient navigation. We defined better-rated navigators as those scoring above the first quartile of mean scores on the Patient Satisfaction with Interpersonal Relationship with Navigator scale. We defined patient satisfaction based on scores above or below the median of the Patient Satisfaction with Cancer-Related Care (PSCC) scale. We controlled for patient and site characteristics using backward selection logistic regression analyses. Among patients with abnormal screening, having a better-rated navigator was associated with higher score on the PSCC (p < 0.05). After controlling for other bivariate predictors of satisfaction (e.g., age, race, income, and household size), navigation by better-rated navigators was associated with a greater likelihood of having higher patient satisfaction [odds ratio (OR), 1.38; 95 % confidence interval (CI), 1.05-1.82]. Similar findings between better-rated navigators and score on the PSCC were found for participants with diagnosed cancer (OR, 3.06; 95 % CI, 1.56-6.0). Patients navigated by better-rated navigators reported higher satisfaction with their cancer-related care.
C1 [Jean-Pierre, Pascal] Harper Canc Res Inst, Notre Dame, IN USA.
[Winters, Paul C.; Fiscella, Kevin] Univ Rochester, Med Ctr, Dept Family Med, Rochester, NY 14642 USA.
[Clark, Jack A.] Boston Univ, Sch Publ Hlth, Ctr Hlth Qual Outcomes & Econ Res VA HSR&D, Boston, MA USA.
[Warren-Mears, Victoria] Tribal Epidemiol Ctr, Northwest Portland Area Indian Hlth Board, Portland, OR USA.
[Wells, Kristen J.] Univ S Florida, Coll Med, Ctr Evidence Based Med & Hlth Outcomes Res, Tampa, FL USA.
[Post, Douglas M.] Ohio State Wexner Med Ctr, Dept Family Med, Columbus, OH USA.
[LaVerda, Nancy] George Washington Univ, Med Ctr, Inst Canc, Washington, DC 20037 USA.
[Van Duyn, Mary Ann] NCI, Ctr Reduce Canc Hlth Dispar, Rockville, MD USA.
[Jean-Pierre, Pascal] Univ Notre Dame, Dept Psychol, Notre Dame, IN 46556 USA.
RP Jean-Pierre, P (reprint author), Univ Notre Dame, Dept Psychol, 109 Haggar Hall, Notre Dame, IN 46556 USA.
EM PJeanpierre@nd.edu
RI Wells, Kristen/J-1838-2012;
OI Clark, Jack/0000-0002-7424-1670
FU Walther Cancer Foundation; National Cancer Institute Center to Reduce
Cancer Health Disparities [3U01CA116924-03S1, U01 CA116924 01,
1R25CA10261801A1, U01CA116892, U01CA117281, U01CA116903, U01CA116937,
U01CA116885, U01CA116875, U01CA116925]; American Cancer Society
[SIRSG-05-253-01]
FX Dr. Pascal Jean-Pierre wishes to acknowledge the support of the Walther
Cancer Foundation. This study was supported by grants from the National
Cancer Institute Center to Reduce Cancer Health Disparities
(3U01CA116924-03S1, U01 CA116924 01, 1R25CA10261801A1, U01CA116892,
U01CA117281, U01CA116903, U01CA116937, U01CA116885, U01CA116875, and
U01CA116925) and the American Cancer Society (SIRSG-05-253-01).
NR 23
TC 2
Z9 2
U1 0
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0885-8195
J9 J CANCER EDUC
JI J. Cancer Educ.
PD SEP
PY 2013
VL 28
IS 3
BP 527
EP 534
DI 10.1007/s13187-013-0498-5
PG 8
WC Oncology; Education, Scientific Disciplines; Public, Environmental &
Occupational Health
SC Oncology; Education & Educational Research; Public, Environmental &
Occupational Health
GA 206JN
UT WOS:000323516400022
PM 23807598
ER
PT J
AU van der Veen, JW
Shen, J
AF van der Veen, Jan Willem
Shen, Jun
TI Regional difference in GABA levels between medial prefrontal and
occipital cortices
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE N-acetylaspartate (NAA); creatine; glutamate + glutamine (Glx);
gamma-aminobutyric acid (GABA); prefrontal cortex; occipital cortex;
white matter; gray matter
ID MAGNETIC-RESONANCE-SPECTROSCOPY; GAMMA-AMINOBUTYRIC-ACID; HUMAN BRAIN;
IN-VIVO; DEPRESSED-PATIENTS; DISORDER; CORTEX
AB Purpose: To avoid the confounding effects of variations in tissue composition this study measured regional GABA differences using two voxels with the same tissue composition.
Materials and Methods: Eighteen healthy adult volunteers were scanned using a 3 Tesla GE clinical scanner with a J-coupling based editing sequence. Spectroscopy voxels were placed in the medial prefrontal (MPFC) and occipital cortex (OCC) with essentially the same gray and white matter fractions.
Results: A 16% (P = 0.0001) significantly higher GABA to creatine ratio was found in the OCC (0.1103 +/- 0.0050) compared with the MPFC (0.0953 +/- 0.0041). When normalized to tissue water, GABA concentrations in the OCC were 14% higher than in the MPFC.
Conclusion: A difference in GABA concentration was found between the OCC and MPFC voxels in healthy subjects which is attributable to differences other than tissue composition. J. Magn. Reson. Imaging 2013;38:745-750. (c) 2013 Wiley Periodicals, Inc.
C1 [van der Veen, Jan Willem; Shen, Jun] NIMH, Magnet Resonance Spectroscopy Core Facil, Bethesda, MD 20892 USA.
[Shen, Jun] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
RP van der Veen, JW (reprint author), NIMH, Magnet Resonance Spectroscopy Core Facil, Bldg 10,Room 2D50,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM veen@nih.gov
FU Intramural Research Program of the National Institute of Mental Health,
National Institutes of Health (IRP-NIMH-NIH)
FX Contract grant sponsor: the Intramural Research Program of the National
Institute of Mental Health, National Institutes of Health
(IRP-NIMH-NIH).
NR 30
TC 10
Z9 10
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-1807
J9 J MAGN RESON IMAGING
JI J. Magn. Reson. Imaging
PD SEP
PY 2013
VL 38
IS 3
BP 745
EP 750
DI 10.1002/jmri.24009
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 208TL
UT WOS:000323702500031
PM 23349060
ER
PT J
AU Yu, FS
Wang, ZF
Tanaka, M
Chiu, CT
Leeds, P
Zhang, YM
Chuang, DM
AF Yu, Fengshan
Wang, Zhifei
Tanaka, Mikiei
Chiu, Chi-Tso
Leeds, Peter
Zhang, Yumin
Chuang, De-Maw
TI Posttrauma cotreatment with lithium and valproate: reduction of lesion
volume, attenuation of blood-brain barrier disruption, and improvement
in motor coordination in mice with traumatic brain injury Laboratory
investigation
SO JOURNAL OF NEUROSURGERY
LA English
DT Article
DE traumatic brain injury; lithium; valproate; neuroprotection;
acetylhistone H3; mouse
ID MOOD STABILIZERS LITHIUM; BIPOLAR DISORDER; MOUSE MODEL; ACID;
INHIBITION; NEURODEGENERATION; DEFICITS; DISEASE; ROLES; HDAC
AB Object. Although traumatic brain injury (TBI) is the leading cause of death and morbidity in young adults, no effective pharmaceutical treatment is available. By inhibiting glycogen synthase kinase-3 (GSK-3) and histone deacetylases (HDACs), respectively, lithium and valproate (VPA) have beneficial effects in diverse neurodegenerative diseases. Furthermore, in an excitotoxic neuronal model and in animal models of amyotrophic lateral sclerosis, Huntington disease, and stroke, combined treatment with lithium and VPA produces more robust neuroprotective effects than treatment with either agent alone. Building on previous work that establishes that therapeutic doses of either lithium or VPA have beneficial effects in mouse models of TBI, this study evaluated the effects of combined treatment with subeffective doses of lithium and VPA in a mouse model of TBI.
Methods. Male C57BL/6 mice underwent TBI and were subsequently treated with lithium, VPA, or a combination of lithium and VPA 15 minutes post-TBI and once daily thereafter for up to 3 weeks; all doses were subeffective (1 mEq/kg of lithium and 200 mg/kg of VPA). Assessed parameters included lesion volume via H & E staining; blood-brain bather (BBB) integrity via immunoglobulin G extravasation; neurodegeneration via Fluoro-Jade B staining; motor coordination via a beam-walk test; and protein levels of acetylhistone H3, phospho-GSK-3 beta, and beta-catenin via Western blotting.
Results. Posttrauma treatment with combined subeffective doses of lithium and VPA significantly reduced lesion volume, attenuated BBB disruption, and mitigated hippocampal neurodegeneration 3 days after TBI. As expected, subeffective doses of lithium or VPA alone did not have these beneficial effects. Combined treatment also improved motor coordination starting from Day 7 and persisting at least 21 days after TBI. Acetylation of histone H3, an index of HDAC inhibition, was robustly increased by the combined treatment 3 days after TBI.
Conclusions. Cotreatment with subeffective doses of lithium and VPA significantly attenuated TBI-induced brain lesion, BBB disruption, and neurodegeneration, and robustly improved long-term functional recovery. These findings suggest that potentiating histone acetylation by HDAC inhibition is probably part of the mechanism underlying the beneficial effects associated with this combined treatment for TBI. Because both lithium and VPA have a long history of safe clinical use, the results suggest that using a combination of these 2 agents at subtherapeutic doses to treat patients with TBI may also reduce side effects and enhance tolerability.
C1 [Yu, Fengshan; Wang, Zhifei; Chiu, Chi-Tso; Leeds, Peter; Chuang, De-Maw] NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
[Yu, Fengshan; Zhang, Yumin; Chuang, De-Maw] Ctr Neurosci & Regenerat Med, Bethesda, MD USA.
[Yu, Fengshan; Tanaka, Mikiei; Zhang, Yumin] Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA.
RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, NIH, 10 Ctr Dr,MSC 1363, Bethesda, MD 20892 USA.
EM chuang@mail.nih.gov
FU Center for Neuroscience and Regenerative Medicine of the Department of
Defense; Blast Lethality Injury and Research Program; Intramural
Research Program of the National Institute of Mental Health, National
Institutes of Health (IRP-NIMH-NIH)
FX This work was funded in part by the Center for Neuroscience and
Regenerative Medicine of the Department of Defense, the Blast Lethality
Injury and Research Program, and the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health
(IRP-NIMH-NIH). The authors have no conflicts of interest to disclose,
financial or otherwise.
NR 28
TC 23
Z9 23
U1 0
U2 14
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 SEP
PY 2013
VL 119
IS 3
BP 766
EP 773
DI 10.3171/2013.6.JNS13135
PG 8
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 204IJ
UT WOS:000323358700029
PM 23848820
ER
PT J
AU Zamora-Ros, R
Rabassa, M
Cherubini, A
Urpi-Sarda, M
Bandinelli, S
Ferrucci, L
Andres-Lacueva, C
AF Zamora-Ros, Raul
Rabassa, Montserrat
Cherubini, Antonio
Urpi-Sarda, Mireia
Bandinelli, Stefania
Ferrucci, Luigi
Andres-Lacueva, Cristina
TI High Concentrations of a Urinary Biomarker of Polyphenol Intake Are
Associated with Decreased Mortality in Older Adults
SO JOURNAL OF NUTRITION
LA English
DT Article
ID NUTRITION EPIC-SPAIN; CARDIOVASCULAR-DISEASE; DIETARY FLAVONOIDS;
CANCER-RISK; MEDITERRANEAN DIET; PHENOLIC-ACIDS; SPANISH COHORT; HUMANS;
FOOD; EXCRETION
AB Polyphenols might have a role in the prevention of several chronic diseases, but evaluating total dietary polyphenol (TDP) intake from self-reported questionnaires is inaccurate and unreliable. A promising alternative is to use total urinary polyphenol (TUP) concentration as a proxy measure of intake. The current study evaluated the relationship between TUPs and TDPs and all-cause mortality during a 12-y period among older adult participants. The study population included 807 men and women aged 65 y and older from the Invecchiare in Chianti study, a population-based cohort study of older adults living in the Chianti region of Tuscany, Italy. TUP concentrations were measured at enrolment (1998-2000) using the Folin-Ciocalteau assay after a solid-phase extraction. TDPs were also estimated at baseline throughout a validated food frequency questionnaire and using our database based on USDA and Phenol-Explorer databases. We modeled associations using Kaplan-Meier survival and Cox proportional hazards models, with adjustment for potential confounders. During the 12-y follow-up, 274 participants (34%) died. At enrollment, TUP excretion adjusted for age and sex tended to be greater in participants who survived 1163 +/- 62 mg gallic acid equivalents (GAE)/d)I than in those who died (143 +/- 63 mg GAE/d) (P = 0.07). However, no significant differences were observed for TDPs. In the multivariable Cox model, participants in the highest tertile of TUP at enrolment had a lower mortality rate than those in the lowest tertile [HR = 0.70 (95% Cl: 0.49-0.99); P-trend = 0.045], whereas no significant associations were found between TDP and overall mortality. TUP is an independent risk factor for mortality among community-dwelling older adults, suggesting that high dietary intake of polyphenols may be associated with longevity.
C1 [Zamora-Ros, Raul; Rabassa, Montserrat; Urpi-Sarda, Mireia; Andres-Lacueva, Cristina] Univ Barcelona, Dept Nutr & Food Sci, XaRTA INSA, INGENIO CONSOLIDER Program,Pharm Sch, Barcelona, Spain.
[Zamora-Ros, Raul] Bellvitge Biomed Res Inst, Catalan Inst Oncol, Unit Nutr Environm & Canc, Barcelona, Spain.
[Cherubini, Antonio] Univ Perugia, Sch Med, Dept Clin & Expt Med, Inst Gerontol & Geriatr, I-06100 Perugia, Italy.
[Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA.
RP Cherubini, A (reprint author), Italian Natl Res Ctr Aging, Geriatr Hosp, Ancona, Italy.
EM a.cherubini@inrca.it
RI Urpi-Sarda, Mireia/D-5937-2013; Andres-Lacueva, Cristina/J-3377-2012;
OI Urpi-Sarda, Mireia/0000-0002-4064-5175; Andres-Lacueva,
Cristina/0000-0002-8494-4978; Cherubini, Antonio/0000-0003-0261-9897
FU Italian Ministry of Health; United States National Institute on Aging;
Spanish Ministry of Science and Innovation [AGL2009-13906-C02-01];
Mapfre Foundation; University of Barcelona; Barcelona Knowledge Campus;
Campus of International Excellence program of the Spanish Ministry of
Education, Culture and Sport; MICINN; European Social Funds; Spanish
postdoctoral programme Fondo de Investigacion Sanitaria [CD09/00133]
FX Supported in part by the Italian Ministry of Health and by the United
States National Institute on Aging. This study was also supported by
grants from the Spanish Ministry of Science and Innovation
(INGENIO-CONSOLIDER program, FUN-C-Food CSD2007-063,
AGL2009-13906-C02-01), the Mapfre Foundation, and the University of
Barcelona, Barcelona Knowledge Campus, Campus of International
Excellence program of the Spanish Ministry of Education, Culture and
Sport. Further support was from MICINN and the European Social Funds [to
the Ramon y Cajal contract (Ramon y Cajal Programme)] and the Spanish
postdoctoral programme Fondo de Investigacion Sanitaria (no.
CD09/00133).
NR 44
TC 12
Z9 12
U1 1
U2 20
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
J9 J NUTR
JI J. Nutr.
PD SEP
PY 2013
VL 143
IS 9
BP 1445
EP 1450
DI 10.3945/jn.113.177121
PG 6
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 205SX
UT WOS:000323466200012
PM 23803472
ER
PT J
AU MacKillop, J
Acker, JD
Bollinger, J
Clifton, A
Miller, JD
Campbell, WK
Goodie, AS
AF MacKillop, James
Acker, John D.
Bollinger, Jared
Clifton, Allan
Miller, Joshua D.
Campbell, W. Keith
Goodie, Adam S.
TI Brief Report: The Brief Alcohol Social Density Assessment (BASDA):
Convergent, Criterion-Related, and Incremental Validity
SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS
LA English
DT Article
ID ADOLESCENT SUBSTANCE USE; DRINKING MOTIVES; CONSTRUCT-VALIDITY;
COLLEGE-STUDENTS; NETWORK ANALYSIS; YOUNG ADULTHOOD; UNITED-STATES;
ABUSE; SWITZERLAND; INVOLVEMENT
AB Objective: Alcohol misuse is substantially influenced by social factors, but systematic assessments of social network drinking are typically lengthy. The goal of the present study was to provide further validation of a brief measure of social network alcohol use, the Brief Alcohol Social Density Assessment (BASDA), in a sample of emerging adults. Specifically, the study sought to examine the BASDA's convergent, criterion, and incremental validity in relation to well-established measures of drinking motives and problematic drinking. Method: Participants were 354 undergraduates who were assessed using the BASDA, the Alcohol Use Disorders Identification Test (AUDIT), and the Drinking Motives Questionnaire. Results: Significant associations were observed between the BASDA index of alcohol-related social density and alcohol misuse, social motives, and conformity motives, supporting convergent validity Criterion-related validity was supported by evidence that significantly greater alcohol involvement was present in the social networks of individuals scoring at or above an AUDIT score of 8, a validated criterion for hazardous drinking. Finally, the BASDA index was significantly associated with alcohol misuse above and beyond drinking motives in relation to AUDIT scores, supporting incremental validity. Conclusions: Taken together, these findings provide further support for the BASDA as an efficient measure of drinking in an individual's social network. Methodological considerations as well as recommendations for future investigations in this area are discussed.
C1 [MacKillop, James; Acker, John D.; Miller, Joshua D.; Campbell, W. Keith; Goodie, Adam S.] Univ Georgia, Dept Psychol, Athens, GA 30602 USA.
[MacKillop, James] Brown Univ, Dept Behav & Social Sci, Providence, RI 02912 USA.
[Bollinger, Jared] NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, Bethesda, MD USA.
[Clifton, Allan] Vassar Coll, Dept Psychol, Poughkeepsie, NY 12601 USA.
RP MacKillop, J (reprint author), Univ Georgia, Dept Psychol, 100 Hooper St, Athens, GA 30602 USA.
EM jmackill@uga.edu
FU National Institutes of Health [K23 AA016936]; National Center for
Responsible Gaming
FX This research was supported by National Institutes of Health Grant K23
AA016936 (J.M.) and the National Center for Responsible Gaming (A.S.G.,
A.C., J.D.M., W.K.C.).
NR 34
TC 1
Z9 1
U1 2
U2 10
PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV
PI PISCATAWAY
PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA
SN 1937-1888
J9 J STUD ALCOHOL DRUGS
JI J. Stud. Alcohol Drugs
PD SEP
PY 2013
VL 74
IS 5
BP 810
EP 815
PG 6
WC Substance Abuse; Psychology
SC Substance Abuse; Psychology
GA 206OG
UT WOS:000323531400019
PM 23948542
ER
PT J
AU Chuang, GY
Acharya, P
Schmidt, SD
Yang, YP
Louder, MK
Zhou, TQ
Do Kwon, Y
Pancera, M
Bailer, RT
Doria-Rose, NA
Nussenzweig, MC
Mascola, JR
Kwong, PD
Georgiev, IS
AF Chuang, Gwo-Yu
Acharya, Priyamvada
Schmidt, Stephen D.
Yang, Yongping
Louder, Mark K.
Zhou, Tongqing
Do Kwon, Young
Pancera, Marie
Bailer, Robert T.
Doria-Rose, Nicole A.
Nussenzweig, Michel C.
Mascola, John R.
Kwong, Peter D.
Georgiev, Ivelin S.
TI Residue-Level Prediction of HIV-1 Antibody Epitopes Based on
Neutralization of Diverse Viral Strains
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID STRUCTURAL BASIS; MONOCLONAL-ANTIBODIES; POTENT NEUTRALIZATION; RATIONAL
DESIGN; BINDING; VIRUS; BROAD; GP120; RECOGNITION; CD4
AB Delineation of antibody epitopes at the residue level is key to understanding antigen resistance mutations, designing epitope-specific probes for antibody isolation, and developing epitope-based vaccines. Ideally, epitope residues are determined in the context of the atomic-level structure of the antibody-antigen complex, though structure determination may in many cases be impractical. Here we describe an efficient computational method to predict antibody-specific HIV-1 envelope (Env) epitopes at the residue level, based on neutralization panels of diverse viral strains. The method primarily utilizes neutralization potency data over a set of diverse viral strains representing the antigen, and enhanced accuracy could be achieved by incorporating information from the unbound structure of the antigen. The method was evaluated on 19 HIV-1 Env antibodies with neutralization panels comprising 181 diverse viral strains and with available antibody-antigen complex structures. Prediction accuracy was shown to improve significantly over random selection, with an average of greater-than-8-fold enrichment of true positives at the 0.05 false-positive rate level. The method was used to prospectively predict epitope residues for two HIV-1 antibodies, 8ANC131 and 8ANC195, for which we experimentally validated the predictions. The method is inherently applicable to antigens that exhibit sequence diversity, and its accuracy was found to correlate inversely with sequence conservation of the epitope. Together the results show how knowledge inherent to a neutralization panel and unbound antigen structure can be utilized for residue-level prediction of antibody epitopes.
C1 [Chuang, Gwo-Yu; Acharya, Priyamvada; Schmidt, Stephen D.; Yang, Yongping; Louder, Mark K.; Zhou, Tongqing; Do Kwon, Young; Pancera, Marie; Bailer, Robert T.; Doria-Rose, Nicole A.; Mascola, John R.; Kwong, Peter D.; Georgiev, Ivelin S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Nussenzweig, Michel C.] Rockefeller Univ, Lab Mol Immunol, New York, NY 10021 USA.
[Nussenzweig, Michel C.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA.
RP Georgiev, IS (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM ivelin.georgiev@nih.gov
RI Zhou, Tongqing/A-6880-2010; Kwon, Young Do/A-6957-2010; Schmidt,
Stephen/B-5398-2012
OI Zhou, Tongqing/0000-0002-3935-4637;
FU Intramural Research Program of the Vaccine Research Center, NIAID;
International AIDS Vaccine Initiative's Neutralizing Antibody
Consortium; Office of AIDS Research, NIH; Bill and Melinda Gates
Foundation [38619s]; NIH [AI 100663-01, AI 100148-01]
FX This work was supported by the Intramural Research Program of the
Vaccine Research Center, NIAID, the International AIDS Vaccine
Initiative's Neutralizing Antibody Consortium, the Office of AIDS
Research, NIH, and the following grants to M.C.N.: Bill and Melinda
Gates Foundation grant 38619s and NIH grants AI 100663-01 and AI
100148-01. M.C.N. is an HHMI investigator.
NR 55
TC 25
Z9 25
U1 0
U2 11
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD SEP
PY 2013
VL 87
IS 18
BP 10047
EP 10058
DI 10.1128/JVI.00984-13
PG 12
WC Virology
SC Virology
GA 205DE
UT WOS:000323420800009
PM 23843642
ER
PT J
AU Stokes, KL
Currier, MG
Sakamoto, K
Lee, S
Collins, PL
Plemper, RK
Moore, ML
AF Stokes, Kate L.
Currier, Michael G.
Sakamoto, Kaori
Lee, Sujin
Collins, Peter L.
Plemper, Richard K.
Moore, Martin L.
TI The Respiratory Syncytial Virus Fusion Protein and Neutrophils Mediate
the Airway Mucin Response to Pathogenic Respiratory Syncytial Virus
Infection
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID NECROSIS-FACTOR-ALPHA; IN-VITRO; MEMBRANE-FUSION; TNF-ALPHA;
INFLAMMATORY PROTEIN-2; EPITHELIAL-CELLS; DISEASE SEVERITY;
GENE-EXPRESSION; INFLUENZA-VIRUS; ALLERGIC-ASTHMA
AB Respiratory syncytial virus (RSV) is the leading cause of death due to a viral etiology in infants. RSV disease is characterized by epithelial desquamation, neutrophilic bronchiolitis and pneumonia, and obstructive pulmonary mucus. It has been shown that infection of BALB/cJ mice with RSV clinical isolate A2001/2-20 (2-20) results in a higher early viral load, greater airway necrosis, and higher levels of interleukin-13 (IL-13) and airway mucin expression than infection with RSV laboratory strain A2. We hypothesized that the fusion (F) protein of RSV 2-20 is a mucus-inducing viral factor. In vitro, the fusion activity of 2-20 F but not that of A2 F was enhanced by expression of RSV G. We generated a recombinant F-chimeric RSV by replacing the F gene of A2 with the F gene of 2-20, generating A2-2-20F. Similar to the results obtained with the parent 2-20 strain, infection of BALB/cJ mice with A2-2-20F resulted in a higher early viral load and higher levels of subsequent pulmonary mucin expression than infection with the A2 strain. A2-2-20F infection induced greater necrotic airway damage and neutrophil infiltration than A2 infection. We hypothesized that the neutrophil response to A2-2-20F infection is involved in mucin expression. Antibody-mediated depletion of neutrophils in RSV-infected mice resulted in lower tumor necrosis factor alpha levels, fewer IL-13-expressing CD4 T cells, and less airway mucin production in the lung. Our data are consistent with a model in which the F and attachment (G) glycoprotein functional interaction leads to enhanced fusion and F is a key factor in airway epithelium infection, pathogenesis, and subsequent airway mucin expression.
C1 [Stokes, Kate L.; Currier, Michael G.; Lee, Sujin; Plemper, Richard K.; Moore, Martin L.] Emory Univ, Dept Pediat, Atlanta, GA 30322 USA.
[Stokes, Kate L.; Currier, Michael G.; Lee, Sujin; Plemper, Richard K.; Moore, Martin L.] Childrens Healthcare Atlanta, Atlanta, GA USA.
[Sakamoto, Kaori] Univ Georgia, Coll Vet Med, Dept Pathol, Athens, GA 30602 USA.
[Collins, Peter L.] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA.
RP Moore, ML (reprint author), Emory Univ, Dept Pediat, Atlanta, GA 30322 USA.
EM martin.moore@emory.edu
FU NIH [1R01AI087798, 1U19AI095227]
FX This work was supported by the following grants: NIH 1R01AI087798 and
NIH 1U19AI095227.
NR 72
TC 29
Z9 31
U1 0
U2 11
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD SEP
PY 2013
VL 87
IS 18
BP 10070
EP 10082
DI 10.1128/JVI.01347-13
PG 13
WC Virology
SC Virology
GA 205DE
UT WOS:000323420800011
PM 23843644
ER
PT J
AU Samal, S
Khattar, SK
Paldurai, A
Palaniyandi, S
Zhu, XP
Collins, PL
Samal, SK
AF Samal, Sweety
Khattar, Sunil K.
Paldurai, Anandan
Palaniyandi, Senthilkumar
Zhu, Xiaoping
Collins, Peter L.
Samal, Siba K.
TI Mutations in the Cytoplasmic Domain of the Newcastle Disease Virus
Fusion Protein Confer Hyperfusogenic Phenotypes Modulating Viral
Replication and Pathogenicity
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HEMAGGLUTININ-NEURAMINIDASE PROTEIN; RESPIRATORY-SYNCYTIAL-VIRUS;
POLARIZED EPITHELIAL-CELLS; PARAMYXOVIRUS-F-PROTEIN; AMINO-ACID CHANGE;
MEMBRANE-FUSION; SORTING SIGNALS; TERMINAL REGION; COILED-COIL;
GLYCOPROTEIN
AB The Newcastle disease virus (NDV) fusion protein (F) mediates fusion of viral and host cell membranes and is a major determinant of NDV pathogenicity. In the present study, we demonstrate the effects of functional properties of F cytoplasmic tail (CT) amino acids on virus replication and pathogenesis. Out of a series of C-terminal deletions in the CT, we were able to rescue mutant viruses lacking two or four residues (r Delta 2 and r Delta 4). We further rescued viral mutants with individual amino acid substitutions at each of these four terminal residues (rM553A, rK552A, rT551A, and rT550A). In addition, the NDV F CT has two conserved tyrosine residues (Y524 and Y527) and a dileucine motif (LL536-537). In other paramyxoviruses, these residues were shown to affect fusion activity and are central elements in basolateral targeting. The deletion of 2 and 4 CT amino acids and single tyrosine substitution resulted in hyperfusogenic phenotypes and increased viral replication and pathogenesis. We further found that in rY524A and rY527A viruses, disruption of the targeting signals did not reduce the expression on the apical or basolateral surface in polarized Madin-Darby canine kidney cells, whereas in double tyrosine mutant, it was reduced on both the apical and basolateral surfaces. Interestingly, in rL536A and rL537A mutants, the F protein expression was more on the apical than on the basolateral surface, and this effect was more pronounced in the rL537A mutant. We conclude that these wild-type residues in the NDV F CT have an effect on regulating F protein biological functions and thus modulating viral replication and pathogenesis.
C1 [Samal, Sweety; Khattar, Sunil K.; Paldurai, Anandan; Palaniyandi, Senthilkumar; Zhu, Xiaoping; Samal, Siba K.] Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
[Collins, Peter L.] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA.
RP Samal, SK (reprint author), Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
EM ssamal@umd.edu
RI Palaniyandi, Senthilkumar/B-9575-2016
FU NIAID [N01A060009]; NIAID, NIH Intramural Research Program
FX This research was supported by NIAID contract no. N01A060009 (85%
support) and NIAID, NIH Intramural Research Program (15% support).
NR 61
TC 10
Z9 11
U1 0
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD SEP
PY 2013
VL 87
IS 18
BP 10083
EP 10093
DI 10.1128/JVI.01446-13
PG 11
WC Virology
SC Virology
GA 205DE
UT WOS:000323420800012
PM 23843643
ER
PT J
AU Martin, C
Buckler-White, A
Wollenberg, K
Kozak, CA
AF Martin, Carrie
Buckler-White, Alicia
Wollenberg, Kurt
Kozak, Christine A.
TI The Avian XPR1 Gammaretrovirus Receptor Is under Positive Selection and
Is Disabled in Bird Species in Contact with Virus-Infected Wild Mice
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID MURINE LEUKEMIA VIRUSES; CELL-SURFACE RECEPTOR; MOUSE XENOTROPIC
GAMMARETROVIRUSES; MUS-MUSCULUS-MOLOSSINUS; HOST-RANGE; HOUSE MICE;
LABORATORY MOUSE; RETROVIRUS XMRV; C VIRUSES; ORIGIN
AB Xenotropic mouse leukemia viruses (X-MLVs) are broadly infectious for mammals except most of the classical strains of laboratory mice. These gammaretroviruses rely on the XPR1 receptor for entry, and the unique resistance of laboratory mice is due to two mutations in different putative XPR1 extracellular loops. Cells from avian species differ in susceptibility to X-MLVs, and 2 replacement mutations in the virus-resistant chicken XPR1 (K496Q and Q579E) distinguish it from the more permissive duck and quail receptors. These substitutions align with the two mutations that disable the laboratory mouse XPR1. Mutagenesis of the chicken and duck genes confirms that residues at both sites are critical for virus entry. Among 32 avian species, the 2 disabling XPR1 mutations are found together only in the chicken, an omnivorous, ground-dwelling fowl that was domesticated in India and/or Southeast Asia, which is also where X-MLV-infected house mice evolved. The receptor-disabling mutations are also present separately in 5 additional fowl and raptor species, all of which are native to areas of Asia populated by the virus-infected subspecies Mus musculus castaneus. Phylogenetic analysis showed that the avian XPR1 gene is under positive selection at sites implicated in receptor function, suggesting a defensive role for XPR1 in the avian lineage. Contact between bird species and virus-infected mice may thus have favored selection of mouse virus-resistant receptor orthologs in the birds, and our data suggest that similar receptor-disabling mutations were fixed in mammalian and avian species exposed to similar virus challenges.
C1 [Martin, Carrie; Buckler-White, Alicia; Kozak, Christine A.] NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA.
[Wollenberg, Kurt] NIAID, Bioinformat & Computat Biosci Branch, Bethesda, MD 20892 USA.
RP Kozak, CA (reprint author), NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA.
EM ckozak@niaid.nih.gov
OI Blanchard, Carrie/0000-0002-1236-4245
FU Intramural Research Program of the NIAID, NIH
FX This work was supported by the Intramural Research Program of the NIAID,
NIH.
NR 71
TC 8
Z9 8
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD SEP
PY 2013
VL 87
IS 18
BP 10094
EP 10104
DI 10.1128/JVI.01327-13
PG 11
WC Virology
SC Virology
GA 205DE
UT WOS:000323420800013
PM 23843647
ER
PT J
AU Pastrana, DV
Ray, U
Magaldi, TG
Schowalter, RM
Cuburu, N
Buck, CB
AF Pastrana, Diana V.
Ray, Upasana
Magaldi, Thomas G.
Schowalter, Rachel M.
Cuburu, Nicolas
Buck, Christopher B.
TI BK Polyomavirus Genotypes Represent Distinct Serotypes with Distinct
Entry Tropism
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HIGH-THROUGHPUT; VIRUS; SEQUENCE; VP1; IDENTIFICATION; GANGLIOSIDES;
VARIABILITY; POPULATIONS; REACTIVITY; MUTATIONS
AB BK polyomavirus (BKV) causes significant urinary tract pathogenesis in immunosuppressed individuals, including kidney and bone marrow transplant recipients. It is currently unclear whether BKV-neutralizing antibodies can moderate or prevent BKV disease. We developed reporter pseudoviruses based on seven divergent BKV isolates and performed neutralization assays on sera from healthy human subjects. The results demonstrate that BKV genotypes I, II, III, and IV are fully distinct serotypes. While nearly all healthy subjects had BKV genotype I-neutralizing antibodies, a majority of subjects did not detectably neutralize genotype III or IV. Surprisingly, BKV subgenotypes Ib1 and Ib2 can behave as fully distinct serotypes. This difference is governed by as few as two residues adjacent to the cellular glycan receptor-binding site on the virion surface. Serological analysis of mice given virus-like particle (VLP)-based BKV vaccines confirmed these findings. Mice administered a multivalent VLP vaccine showed high-titer serum antibody responses that potently cross-neutralized all tested BKV genotypes. Interestingly, each of the neutralization serotypes bound a distinct spectrum of cell surface receptors, suggesting a possible connection between escape from recognition by neutralizing antibodies and cellular attachment mechanisms. The finding implies that different BKV genotypes have different cellular tropisms and pathogenic potentials in vivo. Individuals who are infected with one BKV serotype may remain humorally vulnerable to other BKV serotypes after implementation of T cell immunosuppression. Thus, prevaccinating organ transplant recipients with a multivalent BKV VLP vaccine might reduce the risk of developing posttransplant BKV disease.
C1 [Pastrana, Diana V.; Ray, Upasana; Magaldi, Thomas G.; Schowalter, Rachel M.; Cuburu, Nicolas; Buck, Christopher B.] NCI, Cellular Oncol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Buck, CB (reprint author), NCI, Cellular Oncol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
EM BuckC@mail.nih.gov
OI Buck, Christopher/0000-0003-3165-8094
FU Intramural Research Program of the NIH; Center for Cancer Research; NCI
Director's Intramural Innovation Award Program
FX This work was by the Intramural Research Program of the NIH, with
support from the Center for Cancer Research and the NCI Director's
Intramural Innovation Award Program.
NR 42
TC 25
Z9 25
U1 0
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD SEP
PY 2013
VL 87
IS 18
BP 10105
EP 10113
DI 10.1128/JVI.01189-13
PG 9
WC Virology
SC Virology
GA 205DE
UT WOS:000323420800014
PM 23843634
ER
PT J
AU Acharya, P
Luongo, TS
Georgiev, IS
Matz, J
Schmidt, SD
Louder, MK
Kessler, P
Yang, YP
McKee, K
O'Dell, S
Chen, L
Baty, D
Chames, P
Martin, L
Mascola, JR
Kwong, PD
AF Acharya, Priyamvada
Luongo, Timothy S.
Georgiev, Ivelin S.
Matz, Julie
Schmidt, Stephen D.
Louder, Mark K.
Kessler, Pascal
Yang, Yongping
McKee, Krisha
O'Dell, Sijy
Chen, Lei
Baty, Daniel
Chames, Patrick
Martin, Loic
Mascola, John R.
Kwong, Peter D.
TI Heavy Chain-Only IgG2b Llama Antibody Effects Near-Pan HIV-1
Neutralization by Recognizing a CD4-Induced Epitope That Includes
Elements of Coreceptor- and CD4-Binding Sites
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; CD4 BINDING-SITE; ENVELOPE GLYCOPROTEINS;
STRUCTURAL BASIS; POTENT NEUTRALIZATION; BROAD NEUTRALIZATION; DOMAIN
ANTIBODIES; RECEPTOR-BINDING; GP120 CORE; IMMUNOGENICITY
AB The conserved HIV-1 site of coreceptor binding is protected from antibody-directed neutralization by conformational and steric restrictions. While inaccessible to most human antibodies, the coreceptor site has been shown to be accessed by antibody fragments. In this study, we used X-ray crystallography, surface plasmon resonance, and pseudovirus neutralization to characterize the gp120-envelope glycoprotein recognition and HIV-1 neutralization of a heavy chain-only llama antibody, named JM4. We describe full-length IgG2b and IgG3 versions of JM4 that target the coreceptor-binding site and potently neutralize over 95% of circulating HIV-1 isolates. Contrary to established trends that show improved access to the coreceptor-binding region by smaller antibody fragments, the single-domain (VHH) version of JM4 neutralized less well than the full-length IgG2b version of JM4. The crystal structure at 2.1-angstrom resolution of VHH JM4 bound to HIV-1 YU2 gp120 stabilized in the CD4-bound state by the CD4-mimetic miniprotein, M48U1, revealed a JM4 epitope that combined regions of coreceptor recognition (including the gp120 bridging sheet, V3 loop, and beta 19 strand) with gp120 structural elements involved in recognition of CD4 such as the CD4-binding loop. The structure of JM4 with gp120 thus defines a novel CD4-induced site of vulnerability involving elements of both co-receptor- and CD4-binding sites. The potently neutralizing JM4 IgG2b antibody that targets this newly defined site of vulnerability adds to the expanding repertoire of broadly neutralizing antibodies that effectively neutralize HIV-1 and thereby potentially provides a new template for vaccine development and target for HIV-1 therapy.
C1 [Acharya, Priyamvada; Luongo, Timothy S.; Georgiev, Ivelin S.; Schmidt, Stephen D.; Louder, Mark K.; Yang, Yongping; McKee, Krisha; O'Dell, Sijy; Chen, Lei; Mascola, John R.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Matz, Julie; Baty, Daniel; Chames, Patrick] INSERM, U1068, CRCM, F-13258 Marseille, France.
[Kessler, Pascal; Martin, Loic] CEA, IBiTecS, Serv Ingn Mol Prot, Gif Sur Yvette, France.
RP Kwong, PD (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM acharyap@mail.nih.gov; pdkwong@nih.gov
RI Schmidt, Stephen/B-5398-2012; MARTIN, loic/E-1627-2011; Chames,
Patrick/R-1800-2016;
OI MARTIN, loic/0000-0002-7940-2955; Chames, Patrick/0000-0002-6104-6286;
Baty, Daniel/0000-0001-8443-4444
FU Intramural AIDS Targeted Anti-retroviral Program (IATAP), NIH;
Intramural Research Program of the Vaccine Research Center, National
Institute of Allergy and Infectious Diseases, NIH; Framework Program
[242135]; Agence Nationale de Recherche sur le SIDA (ANRS); ANRS; INSERM
transfert; OSEO; FP7 program NAMDIATREAM; U.S. Department of Energy,
Basic Energy Sciences, Office of Science [W-31-109-Eng-38]
FX Support for this work was provided by the Intramural AIDS Targeted
Anti-retroviral Program (IATAP), NIH, the Intramural Research Program of
the Vaccine Research Center, National Institute of Allergy and
Infectious Diseases, NIH, the Framework Program (FP7/2010-2014) under
grant agreement no. 242135 (CHAARM), and Agence Nationale de Recherche
sur le SIDA (ANRS). J.M. was supported by a fellowship from ANRS. D.B.
and P.C. are members of the IBiSA nanobody platform of CRCM, supported
by INSERM transfert, OSEO, and FP7 program NAMDIATREAM. Use of sector 22
(Southeast Region Collaborative Access team) at the Advanced Photon
Source was supported by the U.S. Department of Energy, Basic Energy
Sciences, Office of Science, under contract number W-31-109-Eng-38.
NR 49
TC 9
Z9 9
U1 1
U2 13
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD SEP
PY 2013
VL 87
IS 18
BP 10173
EP 10181
DI 10.1128/JVI.01332-13
PG 9
WC Virology
SC Virology
GA 205DE
UT WOS:000323420800020
PM 23843638
ER
PT J
AU Maruri-Avidal, L
Weisberg, AS
Moss, B
AF Maruri-Avidal, Liliana
Weisberg, Andrea S.
Moss, Bernard
TI Association of the Vaccinia Virus A11 Protein with the Endoplasmic
Reticulum and Crescent Precursors of Immature Virions
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID NASCENT VIRAL MEMBRANES; ENVELOPE PROTEIN; EXTERNAL SCAFFOLD; F10
KINASE; MORPHOGENESIS; BIOGENESIS; RIFAMPICIN; INSERTION; ENCODES; CELLS
AB The apparent de novo formation of viral membranes within cytoplasmic factories is a mysterious, poorly understood first step in poxvirus morphogenesis. Genetic studies identified several viral proteins essential for membrane formation and the assembly of immature virus particles. Their repression results in abortive replication with the accumulation of dense masses of viroplasm. In the present study, we further characterized one of these proteins, A11, and investigated its association with cellular and viral membranes under normal and abortive replication conditions. We discovered that A11 colocalized in cytoplasmic factories with the endoplasmic reticulum (ER) and L2, another viral protein required for morphogenesis. Confocal microscopy and subcellular fractionation indicated that A11 was not membrane associated in uninfected cells, whereas L2 still colocalized with the ER. Cellfree transcription and translation experiments indicated that both A11 and L2 are tail-anchored proteins that associate post-translationally with membranes and likely require specific cytoplasmic targeting chaperones. Transmission electron microscopy indicated that A11, like L2, associated with crescent membranes and immature virions during normal infection and with vesicles and tubules near masses of dense viroplasm during abortive infection in the absence of the A17 or A14 protein component of viral membranes. When the synthesis of A11 was repressed, "empty" immature-virion-like structures formed in addition to masses of viroplasm. The immature-virion-like structures were labeled with antibodies to A17 and to the D13 scaffold protein and were closely associated with calnexin-labeled ER. These studies revealed similarities and differences between A11 and L2, both of which may be involved in the recruitment of the ER for virus assembly.
C1 [Maruri-Avidal, Liliana; Weisberg, Andrea S.; Moss, Bernard] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
RP Moss, B (reprint author), NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
EM bmoss@nih.gov
FU Division of Intramural Research, NIAID, NIH
FX The research was supported by the Division of Intramural Research,
NIAID, NIH.
NR 50
TC 8
Z9 9
U1 1
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD SEP
PY 2013
VL 87
IS 18
BP 10195
EP 10206
DI 10.1128/JVI.01601-13
PG 12
WC Virology
SC Virology
GA 205DE
UT WOS:000323420800023
PM 23864611
ER
PT J
AU Maldarelli, F
Kearney, M
Palmer, S
Stephens, R
Mican, J
Polis, MA
Davey, RT
Kovacs, J
Shao, W
Rock-Kress, D
Metcalf, JA
Rehm, C
Greer, SE
Lucey, DL
Danley, K
Alter, H
Mellors, JW
Coffin, JM
AF Maldarelli, Frank
Kearney, Mary
Palmer, Sarah
Stephens, Robert
Mican, JoAnn
Polis, Michael A.
Davey, Richard T.
Kovacs, Joseph
Shao, Wei
Rock-Kress, Diane
Metcalf, Julia A.
Rehm, Catherine
Greer, Sarah E.
Lucey, Daniel L.
Danley, Kristen
Alter, Harvey
Mellors, John W.
Coffin, John M.
TI HIV Populations Are Large and Accumulate High Genetic Diversity in a
Nonlinear Fashion
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATITIS-C VIRUS; DRUG-RESISTANCE
MUTATIONS; DYNAMICS IN-VIVO; CHRONIC INFECTION; REVERSE-TRANSCRIPTASE;
PERIPHERAL-BLOOD; VIRAL LOAD; EVOLUTION; TYPE-1
AB HIV infection is characterized by rapid and error-prone viral replication resulting in genetically diverse virus populations. The rate of accumulation of diversity and the mechanisms involved are under intense study to provide useful information to understand immune evasion and the development of drug resistance. To characterize the development of viral diversity after infection, we carried out an in-depth analysis of single genome sequences of HIV pro-pol to assess diversity and divergence and to estimate replicating population sizes in a group of treatment-naive HIV-infected individuals sampled at single (n = 22) or multiple, longitudinal (n = 11) time points. Analysis of single genome sequences revealed nonlinear accumulation of sequence diversity during the course of infection. Diversity accumulated in recently infected individuals at rates 30-fold higher than in patients with chronic infection. Accumulation of synonymous changes accounted for most of the diversity during chronic infection. Accumulation of diversity resulted in population shifts, but the rates of change were low relative to estimated replication cycle times, consistent with relatively large population sizes. Analysis of changes in allele frequencies revealed effective population sizes that are substantially higher than previous estimates of approximately 1,000 infectious particles/infected individual. Taken together, these observations indicate that HIV populations are large, diverse, and slow to change in chronic infection and that the emergence of new mutations, including drug resistance mutations, is governed by both selection forces and drift.
C1 [Maldarelli, Frank; Kearney, Mary; Palmer, Sarah; Danley, Kristen; Coffin, John M.] NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21701 USA.
[Stephens, Robert; Shao, Wei] SAIC, ISP Adv Biomed Comp Ctr, Frederick, MD USA.
[Mican, JoAnn; Polis, Michael A.; Davey, Richard T.; Rock-Kress, Diane; Metcalf, Julia A.; Rehm, Catherine] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Kovacs, Joseph] NIH, Dept Crit Care, Bethesda, MD 20892 USA.
[Greer, Sarah E.; Alter, Harvey] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
[Lucey, Daniel L.] Washington Hosp Ctr, Div Infect Dis, Washington, DC 20010 USA.
[Mellors, John W.] Univ Pittsburgh, Div Infect Dis, Pittsburgh, PA USA.
[Coffin, John M.] Tufts Univ, Dept Mol Biol & Microbiol, Boston, MA 02111 USA.
RP Maldarelli, F (reprint author), NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21701 USA.
EM fmalli@mail.nih.gov
OI Polis, Michael/0000-0002-9151-2268
FU F.M. Kirby Foundation
FX J.M.C. was a research professor of the American Cancer Society with
support from the F.M. Kirby Foundation.
NR 61
TC 25
Z9 27
U1 2
U2 24
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD SEP
PY 2013
VL 87
IS 18
BP 10313
EP 10323
DI 10.1128/JVI.01225-12
PG 11
WC Virology
SC Virology
GA 205DE
UT WOS:000323420800033
PM 23678164
ER
PT J
AU Drosten, C
Seilmaier, M
Corman, VM
Hartmann, W
Scheible, G
Sack, S
Guggemos, W
Kallies, R
Muth, D
Junglen, S
Muller, MA
Haas, W
Guberina, N
Rohnisch, T
Schmid-Wendtner, M
Aldabbagh, S
Dittmer, U
Gold, H
Graf, P
Bonin, F
Rambaut, A
Wendtner, CM
AF Drosten, Christian
Seilmaier, Michael
Corman, Victor M.
Hartmann, Wulf
Scheible, Gregor
Sack, Stefan
Guggemos, Wolfgang
Kallies, Rene
Muth, Doreen
Junglen, Sandra
Muller, Marcel A.
Haas, Walter
Guberina, Nana
Rohnisch, Tim
Schmid-Wendtner, Monika
Aldabbagh, Souhaib
Dittmer, Ulf
Gold, Hermann
Graf, Petra
Bonin, Frank
Rambaut, Andrew
Wendtner, Clemens-Martin
TI Clinical features and virological analysis of a case of Middle East
respiratory syndrome coronavirus infection
SO LANCET INFECTIOUS DISEASES
LA English
DT Article
ID VIRUS; EMC; TROPISM; ASSAY; PCR
AB Background The Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging virus involved in cases and case clusters of severe acute respiratory infection in the Arabian Peninsula, Tunisia, Morocco, France, Italy, Germany, and the UK. We provide a full description of a fatal case of MERS-CoV infection and associated phylogenetic analyses.
Methods We report data for a patient who was admitted to the Klinikum Schwabing (Munich, Germany) for severe acute respiratory infection. We did diagnostic RT-PCR and indirect immunofluorescence. From time of diagnosis, respiratory, faecal, and urine samples were obtained for virus quantification. We constructed a maximum likelihood tree of the five available complete MERS-CoV genomes.
Findings A 73-year-old man from Abu Dhabi, United Arab Emirates, was transferred to Klinikum Schwabing on March 19, 2013, on day 11 of illness. He had been diagnosed with multiple myeloma in 2008, and had received several lines of treatment. The patient died on day 18, due to septic shock. MERS-CoV was detected in two samples of bronchoalveolar fluid. Viral loads were highest in samples from the lower respiratory tract (up to 1.2x10(6) copies per mL). Maximum virus concentration in urine samples was 2691 RNA copies per mL on day 13; the virus was not present in the urine after renal failure on day 14. Stool samples obtained on days 12 and 16 contained the virus, with up to 1031 RNA copies per g (dose to the lowest detection limit of the assay). One of two oronasal swabs obtained on day 16 were positive, but yielded little viral RNA (5370 copies per mL). No virus was detected in blood. The full virus genome was combined with four other available full genome sequences in a maximum likelihood phylogeny, correlating branch lengths with dates of isolation. The time of the common ancestor was halfway through 2011. Addition of novel genome data from an unlinked case treated 6 months previously in Essen, Germany, showed a clustering of viruses derived from Qatar and the United Arab Emirates.
Interpretation We have provided the first complete viral load profile in a case of MERS-CoV infection. MERS-CoV might have shedding patterns that are different from those of severe acute respiratory syndrome and so might need alternative diagnostic approaches.
C1 [Drosten, Christian; Corman, Victor M.; Kallies, Rene; Muth, Doreen; Junglen, Sandra; Muller, Marcel A.; Aldabbagh, Souhaib] Univ Bonn, Med Ctr, Inst Virol, D-53105 Bonn, Germany.
[Seilmaier, Michael; Hartmann, Wulf; Scheible, Gregor; Sack, Stefan; Guggemos, Wolfgang; Schmid-Wendtner, Monika] Klinikum Schwabing, D-80804 Munich, Germany.
[Haas, Walter] Robert Koch Inst, Dept Infect Epidemiol, Berlin, Germany.
[Guberina, Nana] Univ Duisburg Essen, Dept Internal Med, Essen, Germany.
[Dittmer, Ulf] Univ Duisburg Essen, Inst Virol, Essen, Germany.
[Rohnisch, Tim; Schmid-Wendtner, Monika] Interdisziplinares Onkol Zentrum, Munich, Germany.
[Gold, Hermann; Graf, Petra] Dept Hlth & Environm, Munich, Germany.
[Bonin, Frank] Ruhrlandklinik, Dept Intens Care, Essen, Germany.
[Rambaut, Andrew] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh, Midlothian, Scotland.
[Rambaut, Andrew] NIH, Forgarty Int Ctr, Bethesda, MD 20892 USA.
RP Drosten, C (reprint author), Univ Bonn, Med Ctr, Inst Virol, D-53105 Bonn, Germany.
EM drosten@virology-bonn.de; clemens.wendtner@klinikum-muenchen.de
RI Junglen, Sandra/I-3033-2012;
OI Mueller, Marcel/0000-0003-2242-5117; Corman, Victor
Max/0000-0002-3605-0136; Rambaut, Andrew/0000-0003-4337-3707
FU European research project on emerging diseases detection and response
(EMPERIE) [223498]; German Centre for Infection Research and Education;
German research council [01KIO701, DR 772/3-1]
FX This work was supported by a European research project on emerging
diseases detection and response (EMPERIE; contract No 223498). CD has
received infrastructural support from the German Centre for Infection
Research, which included full funding of the position of VC. Virological
analyses were partly support by the German Ministry for Research and
Education and the German research council (grants 01KIO701 and DR
772/3-1). We thank Tobias BIeicker, Sebastian Brunink, Monika
Eschbach-Bludau, Stephan Kallies, Heike Kirberg, Tobias Klant, Ingrid
Kroning, and Astrid Schneider (Institute of Virology, Bonn, Germany) for
excellent technical assistance.
NR 25
TC 142
Z9 150
U1 6
U2 44
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1473-3099
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD SEP
PY 2013
VL 13
IS 9
BP 745
EP 751
DI 10.1016/S1473-3099(13)70154-3
PG 7
WC Infectious Diseases
SC Infectious Diseases
GA 205SU
UT WOS:000323465900019
PM 23782859
ER
PT J
AU Subramanian, S
Chandramouli, GVR
McMillan, A
Gullapalli, RP
Devasahayam, N
Mitchell, JB
Matsumoto, S
Krishna, MC
AF Subramanian, Sankaran
Chandramouli, Gadisetti V. R.
McMillan, Alan
Gullapalli, Rao P.
Devasahayam, Nallathamby
Mitchell, James B.
Matsumoto, Shingo
Krishna, Murali C.
TI Evaluation of partial k-space strategies to speed up time-domain EPR
imaging
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE MRI; time-domain EPR imaging; partial Fourier; partial k-space
acquisition; conjugate symmetry; single-point imaging; homodyne
detection; projection onto convex sets (POCS)
ID ELECTRON-PARAMAGNETIC-RESONANCE; TUMOR OXYGENATION; RECONSTRUCTION; MRI;
RESOLUTION; OPTIMIZATION; TRAJECTORIES; DESIGN; IMAGES; FMRI
AB Narrow-line spin probes derived from the trityl radical have led to the development of fast in vivo time-domain EPR imaging. Pure phase-encoding imaging modalities based on the single-point imaging scheme have demonstrated the feasibility of three-dimensional oximetric images with functional information in minutes. In this article, we explore techniques to improve the temporal resolution and circumvent the relatively short biological half-lives of trityl probes using partial k-space strategies. There are two main approaches: one involves the use of the Hermitian character of the k-space by which only part of the k-space is measured and the unmeasured part is generated using the Hermitian symmetry. This approach is limited in success by the accuracy of numerical estimate of the phase roll in the k-space that corrupts the Hermiticy. The other approach is to measure only a judicially chosen reduced region of k-space (a centrosymmetric ellipsoid region) that more or less accounts for >70% of the k-space energy. Both of these aspects were explored in Fourier transform-EPR imaging with a doubling of scan speed demonstrated by considering ellipsoid geometry of the k-space. Partial k-space strategies help improve the temporal resolution in studying fast dynamics of functional aspects in vivo with infused spin probes. Magn Reson Med 70:745-753, 2013. (c) 2012 Wiley Periodicals, Inc.
C1 [Subramanian, Sankaran; Devasahayam, Nallathamby; Mitchell, James B.; Matsumoto, Shingo; Krishna, Murali C.] NCI, Radiat Biol Branch, CCR, NIH, Bethesda, MD 20892 USA.
[Chandramouli, Gadisetti V. R.] GenEpria Consulting Inc, Columbia, MD USA.
[McMillan, Alan; Gullapalli, Rao P.] Univ Maryland, Sch Med, Dept Diagnost Radiol & Nucl Med, Baltimore, MD 21201 USA.
RP Krishna, MC (reprint author), NCI, Radiat Biol Branch, CCR, NIH, Bldg 10,Room B3B69, Bethesda, MD 20892 USA.
EM murali@helix.nih.gov
FU Intramural NIH HHS [Z01 BC010476-05]
NR 32
TC 4
Z9 4
U1 1
U2 25
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0740-3194
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD SEP
PY 2013
VL 70
IS 3
BP 745
EP 753
DI 10.1002/mrm.24508
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 206SU
UT WOS:000323543600016
PM 23045171
ER
PT J
AU Hiraishi, H
Shin, BS
Udagawa, T
Nemoto, N
Chowdhury, W
Graham, J
Cox, C
Reid, M
Brown, SJ
Asano, K
AF Hiraishi, Hiroyuki
Shin, Byung-Sik
Udagawa, Tsuyoshi
Nemoto, Naoki
Chowdhury, Wasimul
Graham, Jymie
Cox, Christian
Reid, Megan
Brown, Susan J.
Asano, Katsura
TI Interaction between 25S rRNA A Loop and Eukaryotic Translation
Initiation Factor 5B Promotes Subunit Joining and Ensures Stringent AUG
Selection
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID START CODON SELECTION; IN-VIVO; SACCHAROMYCES-CEREVISIAE;
CRYSTAL-STRUCTURE; SITE SELECTION; DNA-DAMAGE; COMPLEX; YEAST; BINDING;
GCN4
AB In yeast, 25S rRNA makes up the major mass and shape of the 60S ribosomal subunit. During the last step of translation initiation, eukaryotic initiation factor 5B (eIF5B) promotes the 60S subunit joining with the 40S initiation complex (IC). Malfunctional 60S subunits produced by misfolding or mutation may disrupt the 40S IC stalling on the start codon, thereby altering the stringency of initiation. Using several point mutations isolated by random mutagenesis, here we studied the role of 25S rRNA in start codon selection. Three mutations changing bases near the ribosome surface had strong effects, allowing the initiating ribosomes to skip both AUG and non-AUG codons: C2879U and U2408C, altering the A loop and P loop, respectively, of the peptidyl transferase center, and G1735A, mapping near a Eukarya-specific bridge to the 40S subunit. Overexpression of eIF5B specifically suppressed the phenotype caused by C2879U, suggesting functional interaction between eIF5B and the A loop. In vitro reconstitution assays showed that C2879U decreased eIF5B-catalyzed 60S subunit joining with a 40S IC. Thus, eIF5B interaction with the peptidyl transferase center A loop increases the accuracy of initiation by stabilizing the overall conformation of the 80S initiation complex. This study provides an insight into the effect of ribosomal mutations on translation profiles in eukaryotes.
C1 [Hiraishi, Hiroyuki; Udagawa, Tsuyoshi; Nemoto, Naoki; Chowdhury, Wasimul; Graham, Jymie; Cox, Christian; Reid, Megan; Brown, Susan J.; Asano, Katsura] Kansas State Univ, Div Biol, Mol Cellular & Dev Biol Program, Manhattan, KS 66506 USA.
[Brown, Susan J.] Kansas State Univ, Div Biol, Arthropod Genom Ctr, Manhattan, KS 66506 USA.
[Shin, Byung-Sik] Eunice Kennedy Shriver NICHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD USA.
RP Asano, K (reprint author), Kansas State Univ, Div Biol, Mol Cellular & Dev Biol Program, Manhattan, KS 66506 USA.
EM kasano@ksu.edu
FU NIH [GM64781]; Kansas COBRE PSF pilot grant; KSU Terry Johnson Cancer
Center; KSU Division of Biology; NCRR [5P20RR016475]; NIGMS
[8P20GM103418]; Intramural Research Program of the National Institutes
of Health; NIH, ARRA
FX This work was supported by NIH R01 grant GM64781 and its ARRA supplement
(K. A.), a Kansas COBRE PSF pilot grant (K. A.), an Innovative Award
from KSU Terry Johnson Cancer Center (K. A.), an internal grant from the
KSU Division of Biology (K. A.), and grants from NCRR (5P20RR016475) and
NIGMS (8P20GM103418) (S.J.B.) and, in part, by the Intramural Research
Program of the National Institutes of Health (B.-S.S. and Thomas E.
Dever).
NR 44
TC 5
Z9 5
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD SEP
PY 2013
VL 33
IS 18
BP 3540
EP 3548
DI 10.1128/MCB.00771-13
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 208BQ
UT WOS:000323651200001
PM 23836883
ER
PT J
AU Lee, BS
Gapud, EJ
Zhang, SC
Dorsett, Y
Bredemeyer, A
George, R
Callen, E
Daniel, JA
Osipovich, O
Oltz, EM
Bassing, CH
Nussenzweig, A
Lees-Miller, S
Hammel, M
Chen, BPC
Sleckman, BP
AF Lee, Baeck-Seung
Gapud, Eric J.
Zhang, Shichuan
Dorsett, Yair
Bredemeyer, Andrea
George, Rosmy
Callen, Elsa
Daniel, Jeremy A.
Osipovich, Oleg
Oltz, Eugene M.
Bassing, Craig H.
Nussenzweig, Andre
Lees-Miller, Susan
Hammel, Michal
Chen, Benjamin P. C.
Sleckman, Barry P.
TI Functional Intersection of ATM and DNA-Dependent Protein Kinase
Catalytic Subunit in Coding End Joining during V(D)J Recombination
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID DOUBLE-STRAND-BREAK; TELANGIECTASIA MUTATED ATM; ATAXIA-TELANGIECTASIA;
SIGNAL JOINT; LYMPHOCYTE DEVELOPMENT; GENOMIC INSTABILITY; NONSENSE
MUTATION; CELL-LINES; PKCS; REPAIR
AB V(D)J recombination is initiated by the RAG endonuclease, which introduces DNA double-strand breaks (DSBs) at the border between two recombining gene segments, generating two hairpin-sealed coding ends and two blunt signal ends. ATM and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) are serine-threonine kinases that orchestrate the cellular responses to DNA DSBs. During V(D) J recombination, ATM and DNA-PKcs have unique functions in the repair of coding DNA ends. ATM deficiency leads to instability of postcleavage complexes and the loss of coding ends from these complexes. DNA-PKcs deficiency leads to a nearly complete block in coding join formation, as DNA-PKcs is required to activate Artemis, the endonuclease that opens hairpin-sealed coding ends. In contrast to loss of DNA-PKcs protein, here we show that inhibition of DNA-PKcs kinase activity has no effect on coding join formation when ATM is present and its kinase activity is intact. The ability of ATM to compensate for DNA-PKcs kinase activity depends on the integrity of three threonines in DNA-PKcs that are phosphorylation targets of ATM, suggesting that ATM can modulate DNA-PKcs activity through direct phosphorylation of DNA-PKcs. Mutation of these threonine residues to alanine (DNA-PKcs(3A)) renders DNA-PKcs dependent on its intrinsic kinase activity during coding end joining, at a step downstream of opening hairpin-sealed coding ends. Thus, DNA-PKcs has critical functions in coding end joining beyond promoting Artemis endonuclease activity, and these functions can be regulated redundantly by the kinase activity of either ATM or DNA-PKcs.
C1 [Lee, Baeck-Seung; Gapud, Eric J.; Dorsett, Yair; Bredemeyer, Andrea; George, Rosmy; Osipovich, Oleg; Oltz, Eugene M.; Sleckman, Barry P.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA.
[Zhang, Shichuan; Chen, Benjamin P. C.] Univ Texas SW Med Ctr Dallas, Dept Radiat Oncol, Div Mol Radiat Biol, Dallas, TX 75390 USA.
[Callen, Elsa; Nussenzweig, Andre] NCI, Lab Genome Integr, NIH, Bethesda, MD 20892 USA.
[Daniel, Jeremy A.] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Prot Res, Copenhagen, Denmark.
[Bassing, Craig H.] Univ Penn, Childrens Hosp Philadelphia, Dept Pathol & Lab Med, Ctr Childhood Canc Res,Div Canc Pathobiol, Philadelphia, PA 19104 USA.
[Bassing, Craig H.] Univ Penn, Dept Pathol & Lab Med, Abramson Family Canc Res Inst, Philadelphia, PA USA.
[Bassing, Craig H.] Univ Penn, Immunol Grad Grp, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Lees-Miller, Susan] Univ Calgary, Dept Biochem & Mol Biol, Calgary, AB, Canada.
[Lees-Miller, Susan] Univ Calgary, Southern Alberta Canc Res Inst, Calgary, AB, Canada.
[Hammel, Michal] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Phys Biosci Div, Berkeley, CA 94720 USA.
RP Sleckman, BP (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA.
EM sleckman@immunology.wustl.edu
RI Daniel, Jeremy/S-4729-2016;
OI Daniel, Jeremy/0000-0002-1981-5571; Bredemeyer,
Andrea/0000-0003-2970-5998
FU National Institutes of Health [CA136470, AI074953, AI47829, CA92584,
GM105404]; Lawrence Berkeley National Lab IDAT program; CIHR [691369]
FX This work was supported by National Institutes of Health grants CA136470
(B. P. S.), AI074953 (B. P. S.), AI47829 (B. P. S.), CA92584 (S. L.-M.
and M. H.), and GM105404 (M. H.). M. H. was also supported by the
Lawrence Berkeley National Lab IDAT program, and S. L.-M. was supported
by CIHR grant 691369.
NR 64
TC 12
Z9 14
U1 0
U2 14
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 SEP
PY 2013
VL 33
IS 18
BP 3568
EP 3579
DI 10.1128/MCB.00308-13
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 208BQ
UT WOS:000323651200003
PM 23836881
ER
PT J
AU Fogel, AI
Dlouhy, BJ
Wang, CX
Ryu, SW
Neutzner, A
Hasson, SA
Sideris, DP
Abeliovich, H
Youle, RJ
AF Fogel, Adam I.
Dlouhy, Brian J.
Wang, Chunxin
Ryu, Seung-Wook
Neutzner, Albert
Hasson, Samuel A.
Sideris, Dionisia P.
Abeliovich, Hagai
Youle, Richard J.
TI Role of Membrane Association and Atg14-Dependent Phosphorylation in
Beclin-1-Mediated Autophagy
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID III PHOSPHATIDYLINOSITOL 3-KINASE; BECLIN 1; SACCHAROMYCES-CEREVISIAE;
ENDOPLASMIC-RETICULUM; TUMOR-SUPPRESSOR; BINDING; PROTEIN; DOMAIN;
YEAST; GENE
AB During autophagy, a double membrane envelops cellular material for trafficking to the lysosome. Human beclin-1 and its yeast homologue, Atg6/Vps30, are scaffold proteins bound in a lipid kinase complex with multiple cellular functions, including autophagy. Several different Atg6 complexes exist, with an autophagy-specific form containing Atg14. However, the roles of Atg14 and beclin-1 in the activation of this complex remain unclear. We here addressed the mechanism of beclin-1 complex activation and reveal two critical steps in this pathway. First, we identified a unique domain in beclin-1, conserved in the yeast homologue Atg6, which is involved in membrane association and, unexpectedly, controls autophagosome size and number in yeast. Second, we demonstrated that human Atg14 is critical in controlling an autophagy-dependent phosphorylation of beclin-1. We map these novel phosphorylation sites to serines 90 and 93 and demonstrate that phosphorylation at these sites is necessary for maximal autophagy. These results help clarify the mechanism of beclin-1 and Atg14 during autophagy.
C1 [Fogel, Adam I.; Dlouhy, Brian J.; Wang, Chunxin; Ryu, Seung-Wook; Neutzner, Albert; Hasson, Samuel A.; Sideris, Dionisia P.; Abeliovich, Hagai; Youle, Richard J.] NINDS, Biochem Sect, NIH, Bethesda, MD 20892 USA.
[Dlouhy, Brian J.] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA.
[Ryu, Seung-Wook] Korea Adv Inst Sci & Technol, Cell Signaling & Bioimaging Lab, Dept Bio & Brain Engn, KAIST Inst BioCentury, Taejon, South Korea.
[Abeliovich, Hagai] Hebrew Univ Jerusalem, Inst Biochem Food Sci & Nutr, IL-76100 Rehovot, Israel.
RP Youle, RJ (reprint author), NINDS, Biochem Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM youler@ninds.nih.gov
RI Wang, Chunxin/B-9312-2016;
OI Wang, Chunxin/0000-0001-6015-6806; Neutzner, Albert/0000-0001-9254-5558
FU NINDS; National Institutes of Health; Israel Science Fund [1016/07]
FX This work was supported by the NINDS, National Institutes of Health, and
by Israel Science Fund grant 1016/07 (to H.A.).
NR 39
TC 28
Z9 34
U1 0
U2 8
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 SEP
PY 2013
VL 33
IS 18
BP 3675
EP 3688
DI 10.1128/MCB.00079-13
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 208BQ
UT WOS:000323651200011
PM 23878393
ER
PT J
AU Taylor, JE
Pacheco, MA
Bacon, DJ
Beg, MA
Machado, RL
Fairhurst, RM
Herrera, S
Kim, JY
Menard, D
Povoa, MM
Villegas, L
Mulyanto
Snounou, G
Cui, LW
Zeyrek, FY
Escalante, AA
AF Taylor, Jesse E.
Pacheco, M. Andreina
Bacon, David J.
Beg, Mohammad A.
Machado, Ricardo Luiz
Fairhurst, Rick M.
Herrera, Socrates
Kim, Jung-Yeon
Menard, Didier
Povoa, Marinete Marins
Villegas, Leopoldo
Mulyanto
Snounou, Georges
Cui, Liwang
Zeyrek, Fadile Yildiz
Escalante, Ananias A.
TI The Evolutionary History of Plasmodium vivax as Inferred from
Mitochondrial Genomes: Parasite Genetic Diversity in the Americas
SO MOLECULAR BIOLOGY AND EVOLUTION
LA English
DT Article
DE molecular clock; population structure; demographic history
ID HUMAN MALARIA PARASITE; ANCIENT POPULATION EXPANSION; DNA POLYMORPHISM
DATA; SOUTH-AMERICA; FALCIPARUM; ORIGIN; AMAZON; ASIA; ELIMINATION;
HUMANS
AB Plasmodium vivax is the most prevalent human malaria parasite in the Americas. Previous studies have contrasted the genetic diversity of parasite populations in the Americas with those in Asia and Oceania, concluding that New World populations exhibit low genetic diversity consistent with a recent introduction. Here we used an expanded sample of complete mitochondrial genome sequences to investigate the diversity of P. vivax in the Americas as well as in other continental populations. We show that the diversity of P. vivax in the Americas is comparable to that in Asia and Oceania, and we identify several divergent clades circulating in South America that may have resulted from independent introductions. In particular, we show that several haplotypes sampled in Venezuela and northeastern Brazil belong to a clade that diverged from the other P. vivax lineages at least 30,000 years ago, albeit not necessarily in the Americas. We propose that, unlike in Asia where human migration increases local genetic diversity, the combined effects of the geographical structure and the low incidence of vivax malaria in the Americas has resulted in patterns of low local but high regional genetic diversity. This could explain previous views that P. vivax in the Americas has low genetic diversity because these were based on studies carried out in limited areas. Further elucidation of the complex geographical pattern of P. vivax variation will be important both for diversity assessments of genes encoding candidate vaccine antigens and in the formulation of control and surveillance measures aimed at malaria elimination.
C1 [Taylor, Jesse E.; Pacheco, M. Andreina; Escalante, Ananias A.] Arizona State Univ, Biodesign Inst, Ctr Evolutionary Med & Informat, Tempe, AZ 85287 USA.
[Bacon, David J.] Naval Res Lab, Washington, DC USA.
[Beg, Mohammad A.] Aga Khan Univ, Dept Pathol & Microbiol, Karachi, Pakistan.
[Machado, Ricardo Luiz] Fac Med Sao Jose do Rio Preto, Ctr Invest Microrganismos, Dept Doencas Dermatol Infecciosas & Parasitarias, Sao Paulo, Brazil.
[Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
[Herrera, Socrates] Univ Valle, Caucaseco Sci Res Ctr, Inst Immunol, Cali, Colombia.
[Kim, Jung-Yeon] Korea Ctr Dis Control & Prevent, Div Malaria & Parasit Dis, Osong, South Korea.
[Menard, Didier] Inst Pasteur Cambodge, Phnom Penh, Cambodia.
[Povoa, Marinete Marins] Evandro Chagas Inst, Belem, Para, Brazil.
[Villegas, Leopoldo] ICF Int, Int Hlth & Dev Div, Calverton, MD USA.
[Mulyanto] Univ Mataram, Fac Med, Immunobiol Lab, Mataram, Indonesia.
[Snounou, Georges] Univ Paris 06, Paris, France.
[Snounou, Georges] INSERM, Paris, France.
[Cui, Liwang] Penn State Univ, Dept Entomol, University Pk, PA 16802 USA.
[Zeyrek, Fadile Yildiz] Harran Univ, Sch Med, Dept Microbiol, Sanliurfa, Turkey.
[Escalante, Ananias A.] Arizona State Univ, Sch Life Sci, Tempe, AZ 85287 USA.
RP Escalante, AA (reprint author), Arizona State Univ, Biodesign Inst, Ctr Evolutionary Med & Informat, Tempe, AZ 85287 USA.
EM Ananias.Escalante@asu.edu
RI Menard, Didier/O-3294-2013; Dantas Machado, Ricardo Luiz/P-1288-2014
OI Menard, Didier/0000-0003-1357-4495; Dantas Machado, Ricardo
Luiz/0000-0002-8955-3204
FU US National Institutes of Health [R01 GM080586]; Latin American Center
for Malaria Research and Control [U19AI089702]; National Institute of
Allergy and Infectious Diseases
FX The authors thank the DNA laboratory at the School of Life Sciences for
their technical support. This work was supported by the US National
Institutes of Health (R01 GM080586 to A.A.E., the Latin American Center
for Malaria Research and Control U19AI089702, and the Intramural
Research Program of the National Institute of Allergy and Infectious
Diseases to R.M.F.). The content of this article is solely the
responsibility of the authors and does not represent the views of the US
National Institutes of Health.
NR 61
TC 32
Z9 32
U1 1
U2 33
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0737-4038
EI 1537-1719
J9 MOL BIOL EVOL
JI Mol. Biol. Evol.
PD SEP
PY 2013
VL 30
IS 9
BP 2050
EP 2064
DI 10.1093/molbev/mst104
PG 15
WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
Heredity
GA 207QE
UT WOS:000323616600006
PM 23733143
ER
PT J
AU Tarazona-Santos, E
Machado, M
Magalhaes, WCS
Chen, R
Lyon, F
Burdett, L
Crenshaw, A
Fabbri, C
Pereira, L
Pinto, L
Redondo, RAF
Sestanovich, B
Yeager, M
Chanock, SJ
AF Tarazona-Santos, Eduardo
Machado, Moara
Magalhaes, Wagner C. S.
Chen, Renee
Lyon, Fernanda
Burdett, Laurie
Crenshaw, Andrew
Fabbri, Cristina
Pereira, Latife
Pinto, Laelia
Redondo, Rodrigo A. F.
Sestanovich, Ben
Yeager, Meredith
Chanock, Stephen J.
TI Evolutionary Dynamics of the Human NADPH Oxidase Genes CYBB, CYBA, NCF2,
and NCF4: Functional Implications
SO MOLECULAR BIOLOGY AND EVOLUTION
LA English
DT Article
DE innate immunity; immunogenetics; chronic granulomatous disease
ID NATURAL-SELECTION; HUMAN GENOME; POPULATION-GENETICS; DNA-SEQUENCE;
DISEASE; POLYMORPHISM; ASSOCIATION; MAP; SUSCEPTIBILITY; MUTATIONS
AB The phagocyte NADPH oxidase catalyzes the reduction of O-2 to reactive oxygen species with microbicidal activity. It is composed of two membrane-spanning subunits, gp91-phox and p22-phox (encoded by CYBB and CYBA, respectively), and three cytoplasmic subunits, p40-phox, p47-phox, and p67-phox (encoded by NCF4, NCF1, and NCF2, respectively). Mutations in any of these genes can result in chronic granulomatous disease, a primary immunodeficiency characterized by recurrent infections. Using evolutionary mapping, we determined that episodes of adaptive natural selection have shaped the extracellular portion of gp91-phox during the evolution of mammals, which suggests that this region may have a function in host-pathogen interactions. On the basis of a resequencing analysis of approximately 35 kb of CYBB, CYBA, NCF2, and NCF4 in 102 ethnically diverse individuals (24 of African ancestry, 31 of European ancestry, 24 of Asian/Oceanians, and 23 US Hispanics), we show that the pattern of CYBA diversity is compatible with balancing natural selection, perhaps mediated by catalase-positive pathogens. NCF2 in Asian populations shows a pattern of diversity characterized by a differentiated haplotype structure. Our study provides insight into the role of pathogen-driven natural selection in an innate immune pathway and sheds light on the role of CYBA in endothelial, nonphagocytic NADPH oxidases, which are relevant in the pathogenesis of cardiovascular and other complex diseases.
C1 [Tarazona-Santos, Eduardo; Chen, Renee; Sestanovich, Ben; Chanock, Stephen J.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Gaithersburg, MD USA.
[Tarazona-Santos, Eduardo; Machado, Moara; Magalhaes, Wagner C. S.; Lyon, Fernanda; Pereira, Latife; Pinto, Laelia] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Biol Geral, Belo Horizonte, MG, Brazil.
[Burdett, Laurie; Crenshaw, Andrew; Yeager, Meredith] NCI FCRDC, Intramural Res Support Program, SAIC Frederick, Frederick, MD USA.
[Burdett, Laurie; Crenshaw, Andrew; Yeager, Meredith] NCI, Core Genotype Facil, NIH, Gaithersburg, MD USA.
[Fabbri, Cristina] Univ Bologna, Dipartimento Biol Evoluzionist Sperimentale, Bologna, Italy.
[Redondo, Rodrigo A. F.] IST Austria, A-3400 Klosterneuburg, Austria.
RP Tarazona-Santos, E (reprint author), NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Gaithersburg, MD USA.
EM edutars@icb.ufmg.br; chanocks@mail.nih.gov
RI Magalhaes, Wagner/D-8822-2015
FU National Cancer Institute (NCI); National Institutes of Health (NIH);
University of Bologna; Fogarty International Center; National Cancer
Institute [1R01TW007894]; Conselho Nacional de Desenvolvimento
Cientifico e Tecnologico (Brazil) [307556/2012-3]
FX S.J.C. conceived the study; E. T.-S., M. M., F. L., R. C., A. C., C. F.,
L. P., and B. S. generated the data/analyzed the sequences; L. B., A.
C., W. C. S. M., and M.Y. provided tools for data generation and
analyses; E. T.-S., M. M., F. L., W. C. S. M., and R. R. performed
population genetics analyses; E. T.-S. and M. M. prepared tables and
figures; E. T.-S. and S.J.C. wrote the manuscript. All the authors
contributed with discussions about the results. The authors are grateful
to Silvia Fuselli for discussions of our results, to Fernando Levi
Soares for technical assistance with the figures and the Sequencing
Group of the Core Genotyping Facility (National Cancer Institute) for
their technical assistance. This work was supported by the Intramural
Research Program of the National Cancer Institute (NCI) and National
Institutes of Health (NIH). C. F. was supported by the University of
Bologna. E. T-S., M. M., W. C. S. M., and F. L. were supported by the
Fogarty International Center and National Cancer Institute
(1R01TW007894), Conselho Nacional de Desenvolvimento Cientifico e
Tecnologico (Brazil, Grant 307556/2012-3), Fundacao de Amparo a Pesquisa
de Minas Gerais (Brazil, CBB PPM 00265/12) and the Brazilian Ministry of
Education (CAPES Agency, grant PNPD 02567/09-1).
NR 59
TC 5
Z9 5
U1 0
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0737-4038
J9 MOL BIOL EVOL
JI Mol. Biol. Evol.
PD SEP
PY 2013
VL 30
IS 9
BP 2157
EP 2167
DI 10.1093/molbev/mst119
PG 11
WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
Heredity
GA 207QE
UT WOS:000323616600014
PM 23821607
ER
PT J
AU Shrivastav, S
Zhang, LY
Okamoto, K
Lee, H
Lagranha, C
Abe, Y
Balasubramanyam, A
Lopaschuk, GD
Kino, T
Kopp, JB
AF Shrivastav, Shashi
Zhang, Liyan
Okamoto, Koji
Lee, Hewang
Lagranha, Claudia
Abe, Yoshifusa
Balasubramanyam, Ashok
Lopaschuk, Gary D.
Kino, Tomoshige
Kopp, Jeffrey B.
TI HIV-1 Vpr Enhances PPAR beta/delta-Mediated Transcription, Increases
PDK4 Expression, and Reduces PDC Activity
SO MOLECULAR ENDOCRINOLOGY
LA English
DT Article
ID PROLIFERATOR-ACTIVATED RECEPTORS; VIRAL PROTEIN-R;
PYRUVATE-DEHYDROGENASE COMPLEX; FATTY-ACIDS; SKELETAL-MUSCLE;
METABOLISM; MECHANISMS; DELTA; GAMMA; RESPONSES
AB HIV infection and its therapy are associated with disorders of lipid metabolism and bioenergetics. Previous work has suggested that viral protein R (Vpr) may contribute to the development of lipodystrophy and insulin resistance observed in HIV-1-infected patients. In adipocytes, Vpr suppresses mRNA expression of peroxisomal proliferator-activating receptor-gamma (PPAR gamma)-responsive genes and inhibits differentiation. We investigated whether Vpr might interact with PPAR beta/delta and influence its transcriptional activity. In the presence of PPAR beta/delta, Vpr induced a 3.3-fold increase in PPAR response element-driven transcriptional activity, a 1.9-fold increase in pyruvate dehydrogenase kinase 4 (PDK4) protein expression, and a 1.6-fold increase in the phosphorylated pyruvate dehydrogenase subunit E1 alpha leading to a 47% decrease in the activity of the pyruvate dehydrogenase complex in HepG2 cells. PPAR beta/delta knockdown attenuated Vpr-induced enhancement of endogenous PPAR beta/delta-responsive PDK4 mRNA expression. Vpr induced a 1.3-fold increase in mRNA expression of both carnitine palmitoyltransferase vertical bar (CPT1) and acetyl-coenzyme A acyltransferase 2 (ACAA2) and doubled the activity of beta-hydroxylacyl coenzyme A dehydrogenase (HADH). Vpr physically interacted with the ligand-binding domain of PPAR beta/delta in vitro and in vivo. Consistent with a role in energy expenditure, Vpr increased state-3 respiration in isolated mitochondria (1.16-fold) and basal oxygen consumption rate in intact HepG2 cells (1.2-fold) in an etomoxir-sensitive manner, indicating that the oxygen consumption rate increase is beta-oxidation-dependent. The effects of Vpr on PPAR response element activation, pyruvate dehydrogenase complex activity, and beta-oxidation were reversed by specific PPAR beta/delta antagonists. These results support the hypothesis that Vpr contributes to impaired energy metabolism and increased energy expenditure in HIV patients.
C1 [Shrivastav, Shashi; Okamoto, Koji; Lee, Hewang; Abe, Yoshifusa; Kopp, Jeffrey B.] NIDDK, Kidney Dis Sect, Bethesda, MD 20892 USA.
[Lagranha, Claudia] NHLBI, Lab Cardiac Physiol, Bethesda, MD 20892 USA.
[Kino, Tomoshige] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Unit Mol Hormone Act, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
[Zhang, Liyan; Lopaschuk, Gary D.] Univ Alberta, Mazankowski Alberta Heart Inst, Cardiovasc Res Ctr, Edmonton, AB, Canada.
[Balasubramanyam, Ashok] Baylor Coll Med, Diabet Res Ctr, Div Diabet Endocrinol & Metab, Houston, TX 77030 USA.
[Lee, Hewang] Univ Maryland, Sch Med, Dept Med, Div Nephrol, Baltimore, MD 21201 USA.
RP Kopp, JB (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA.
EM jbkopp@nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases;
National Heart Lung and Blood Institute; Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health, Bethesda, Maryland; Baylor College of Medicine Diabetes Research
Center [P30-DK079638, 5P01HL074940-08]; University of Maryland School of
Medicine; Children's National Medical Center; [R01-DK081553]
FX This study was funded in part by the Intramural Research Programs of the
National Institute of Diabetes and Digestive and Kidney Diseases, the
National Heart Lung and Blood Institute and the Eunice Kennedy Shriver
National Institute of Child Health and Human Development, National
Institutes of Health, Bethesda, Maryland. Support was also provided by
R01-DK081553 (to A. B.) and the Baylor College of Medicine Diabetes
Research Center P30-DK079638 and by 5P01HL074940-08 (principal
investigator, R. A. Felder; Project 3 principal investigator, P. A.
Jose), University of Maryland School of Medicine Start-up Funds, and
Children's National Medical Center Intramural Avery award (to H.L.).
NR 38
TC 6
Z9 6
U1 1
U2 8
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0888-8809
J9 MOL ENDOCRINOL
JI Mol. Endocrinol.
PD SEP
PY 2013
VL 27
IS 9
BP 1564
EP 1576
DI 10.1210/me.2012-1370
PG 13
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 209NN
UT WOS:000323765200016
PM 23842279
ER
PT J
AU Rodriguez-Gil, JL
Larson, DM
Wassif, CA
Yanjanin, NM
Anderson, SM
Kirby, MR
Trivedi, NS
Porter, FD
Pavan, WJ
AF Rodriguez-Gil, Jorge L.
Larson, Denise M.
Wassif, Christopher A.
Yanjanin, Nicole M.
Anderson, Stacie M.
Kirby, Martha R.
Trivedi, Niraj S.
Porter, Forbes D.
Pavan, William J.
TI A somatic cell defect is associated with the onset of neurological
symptoms in a lysosomal storage disease
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE Niemann-Pick disease, type C1; NPC1; Lysosomal storage disorders;
Neurodegenerative disorders
ID NIEMANN-PICK-DISEASE; CHOLESTEROL REDUCTION
AB Mutations in individuals with the lysosomal storage disorder Niemann-Pick disease, type C1 (NPC1) are heterogeneous, not localized to specific protein domains, and not correlated to time of onset or disease severity. We demonstrate direct correlation of the time of neurological symptom onset with the severity of lysosomal defects in NPC1 patient-derived fibroblasts. This is a novel assay for NPC1 individuals that may be predictive of NPC1 disease progression and broadly applicable to other lysosomal disorders. Published by Elsevier Inc.
C1 [Rodriguez-Gil, Jorge L.; Larson, Denise M.; Pavan, William J.] NHGRI, Genet Dis Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Wassif, Christopher A.; Yanjanin, Nicole M.; Porter, Forbes D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Anderson, Stacie M.; Kirby, Martha R.] NHGRI, Flow Cytometry Core, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Trivedi, Niraj S.] NHGRI, Genome Technol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Pavan, WJ (reprint author), NHGRI, Genet Dis Res Branch, NIH, 49 Convent Dr,Room 4A82, Bethesda, MD 20892 USA.
EM bpavan@mail.nih.gov
OI Wassif, Christopher/0000-0002-2524-1420
FU National Human Genome Research Institute, National Institutes of Health;
Eunice Kennedy Shriver National Institute of Child Health and Human
Development; Ara Parseghian Medical Research Foundation; Office of Rare
Diseases; National Institutes of Health Clinical Center
FX We thank Cynthia J. Tifft for helpful discussions, Laura Baxter for
editing the manuscript Stephen Wincovitch for support in
imaging/microscopy, Larry N. Singh for assistance in mutation analysis
software and the contributions of the caretakers, patients, and their
families who participated in this study. This work was supported by the
intramural research program of the National Human Genome Research
Institute, National Institutes of Health, the intramural research
program of the Eunice Kennedy Shriver National Institute of Child Health
and Human Development, the Ara Parseghian Medical Research Foundation,
and a Bench to Bedside award from the Office of Rare Diseases and the
National Institutes of Health Clinical Center.
NR 10
TC 1
Z9 1
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 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD SEP-OCT
PY 2013
VL 110
IS 1-2
BP 188
EP 190
DI 10.1016/j.ymgme.2013.06.010
PG 3
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 209ZP
UT WOS:000323799400028
PM 23850077
ER
PT J
AU Gold, PW
AF Gold, P. W.
TI Evidence that stress per se has a role in the precipitation and natural
history of depressive illness
SO MOLECULAR PSYCHIATRY
LA English
DT Editorial Material
ID MAJOR DEPRESSION; HIPPOCAMPAL NEUROGENESIS; LIFE EVENTS; BIOCHEMICAL
MANIFESTATIONS; SIGNALING PATHWAYS; BLOOD-COAGULATION; SOCIAL SUPPORT;
SERUM-LEVELS; WOMEN; DISORDER
C1 NIMH, Bethesda, MD 20892 USA.
RP Gold, PW (reprint author), NIMH, Bethesda, MD 20892 USA.
EM PhilipGold@mail.nih.gov
NR 29
TC 2
Z9 2
U1 0
U2 12
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD SEP
PY 2013
VL 18
IS 9
BP 954
EP 956
DI 10.1038/mp.2013.85
PG 3
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 207JS
UT WOS:000323595300002
PM 23969379
ER
PT J
AU Grillon, C
Krimsky, M
Charney, DR
Vytal, K
Ernst, M
Cornwell, B
AF Grillon, C.
Krimsky, M.
Charney, D. R.
Vytal, K.
Ernst, M.
Cornwell, B.
TI Oxytocin increases anxiety to unpredictable threat
SO MOLECULAR PSYCHIATRY
LA English
DT Letter
ID CENTRAL AMYGDALA; FEAR; HUMANS
C1 [Grillon, C.; Krimsky, M.; Charney, D. R.; Vytal, K.; Cornwell, B.] NIMH, Neurobiol Fear & Anxiety Sect, Intramural Res Program, Bethesda, MD 20892 USA.
[Ernst, M.] NIMH, Emot Dev & Affect Neurosci Branch, Intramural Res Program, Bethesda, MD 20892 USA.
RP Grillon, C (reprint author), NIMH, Neurobiol Fear & Anxiety Sect, Intramural Res Program, Bethesda, MD 20892 USA.
EM christian.grillon@nih.gov
FU Intramural NIH HHS [ZIA MH002798-12]; NIMH NIH HHS [Z01 MH002798]
NR 10
TC 43
Z9 43
U1 2
U2 28
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD SEP
PY 2013
VL 18
IS 9
BP 958
EP 960
DI 10.1038/mp.2012.156
PG 4
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 207JS
UT WOS:000323595300004
PM 23147382
ER
PT J
AU Silverman, MN
Mukhopadhyay, P
Belyavskaya, E
Tonelli, LH
Revenis, BD
Doran, JH
Ballard, BE
Tam, J
Pacher, P
Sternberg, EM
AF Silverman, M. N.
Mukhopadhyay, P.
Belyavskaya, E.
Tonelli, L. H.
Revenis, B. D.
Doran, J. H.
Ballard, B. E.
Tam, J.
Pacher, P.
Sternberg, E. M.
TI Glucocordwticoid receptor dimerization is required for proper recovery
of LPS-induced inflammation, sickness behavior and metabolism in mice
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE cytokine; depression; hippocampus; HPA axis; hypothalamus;
thermoregulation
ID PITUITARY-ADRENAL AXIS; CENTRAL-NERVOUS-SYSTEM; ENDOGENOUS
GLUCOCORTICOIDS PROTECT; INNATE IMMUNE-SYSTEM; GENE-EXPRESSION; KAPPA-B;
MAJOR DEPRESSION; VIRAL-INFECTION; DNA-BINDING; PHYSIOLOGICAL-RESPONSES
AB Endogenous glucocorticoids are essential for mobilizing energy resources, restraining inflammatory responses and coordinating behavior to an immune challenge. Impaired glucocorticoid receptor (GR) function has been associated with impaired metabolic processes, enhanced inflammation and exaggerated sickness and depressive-like behaviors. To discern the molecular mechanisms underlying GR regulation of physiologic and behavioral responses to a systemic immune challenge, GR(dim) mice, in which absent GR dimerization leads to impaired GR-DNA-binding-dependent mechanisms but intact GR protein-protein interactions, were administered low-dose lipopolysaccharide (LPS). GR(dim)-LPS mice exhibited elevated and prolonged levels of plasma corticosterone (CORT), interleukin (IL)-6 and IL-10 (but not plasma tumor necrosis factor-a (TNF alpha)), enhanced early expression of brain TNF alpha, IL-1 beta and IL-6 mRNA levels, and impaired later central TNFa mRNA expression. Exaggerated sickness behavior (lethargy, piloerection, ptosis) in the GR(dim)-LPS mice was associated with increased early brain proinflammatory cytokine expression and late plasma CORT levels, but decreased late brain TNF alpha expression. GR(dim)-LPS mice also exhibited sustained locomotor impairment in the open field, body weight loss and metabolic alterations measured by indirect calorimetry, as well as impaired thermoregulation. Taken together, these data indicate that GR dimerization-dependent DNA-binding mechanisms differentially regulate systemic and central cytokine expression in a cytokine-and time-specific manner, and are essential for the proper regulation and recovery of multiple physiologic responses to low-dose endotoxin. Moreover, these results support the concept that GR protein-protein interactions are not sufficient for glucocorticoids to exert their full anti-inflammatory effects and suggest that glucocorticoid responses limited to GR monomer-mediated transcriptional effects could predispose individuals to prolonged behavioral and metabolic sequelae of an enhanced inflammatory state.
C1 [Silverman, M. N.; Belyavskaya, E.; Revenis, B. D.; Doran, J. H.; Ballard, B. E.; Sternberg, E. M.] NIMH, Sect Neuroendocrine Immunol & Behav, NIH, Bethesda, MD 20892 USA.
[Mukhopadhyay, P.; Tam, J.; Pacher, P.] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD USA.
[Tonelli, L. H.] Univ Maryland, Sch Med, Dept Psychiat, Mood & Anxiety Program, Baltimore, MD 21201 USA.
[Sternberg, E. M.] Univ Arizona, Coll Med, Arizona Ctr Integrat Med, Tucson, AZ 85724 USA.
RP Sternberg, EM (reprint author), Univ Arizona, Coll Med, Arizona Ctr Integrat Med, POB 245153, Tucson, AZ 85724 USA.
EM esternberg@email.arizona.edu
RI Pacher, Pal/B-6378-2008; MUKHOPADHYAY, PARTHA/G-3890-2010
OI Pacher, Pal/0000-0001-7036-8108; MUKHOPADHYAY,
PARTHA/0000-0002-1178-1274
FU NIH (National Institute of Mental Health (NIMH)); NIH (National
Institute on Alcohol Abuse and Alcoholism (NIAAA)); Henry M Jackson
Foundation (Bethesda, MD, USA); Center for Neuroscience and Regenerative
Medicine (Uniformed Services University of the Health Sciences,
Bethesda, MD, USA)
FX This work was supported by the NIH (intramural funds from the National
Institute of Mental Health (NIMH) to EM Sternberg and from the National
Institute on Alcohol Abuse and Alcoholism (NIAAA) to P Pacher).
Additional support was received by the Henry M Jackson Foundation
(Bethesda, MD, USA-MNS salary) and the Center for Neuroscience and
Regenerative Medicine (Uniformed Services University of the Health
Sciences, Bethesda, MD, USA). We thank Dr Gunther Schutz (German Cancer
Research Centre, Heidelberg, Germany) for providing homozygous
GRdim mouse breeder pairs to Taconic Farms (Rockville, MD,
USA). We also thank Laura Tucker (Uniformed Services University of the
Health Sciences, Center for Neuroscience and Regenerative Medicine,
Mouse Behavioral Assessment Core, Bethesda, MD, USA) for instruction on
the ANY-maze software used to analyze our open field data and Dr Sandor
Batkai (Laboratory of Physiologic Studies, NIAAA, NIH, Bethesda, MD,
USA) for setting up the metabolic chambers.
NR 106
TC 15
Z9 16
U1 2
U2 18
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD SEP
PY 2013
VL 18
IS 9
BP 1006
EP 1017
DI 10.1038/mp.2012.131
PG 12
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 207JS
UT WOS:000323595300011
PM 23089634
ER
PT J
AU Lee, SH
Ripke, S
Neale, BM
Faraone, SV
Purcell, SM
Perlis, RH
Mowry, BJ
Thapar, A
Goddard, ME
Witte, JS
Absher, D
Agartz, I
Akil, H
Amin, F
Andreassen, OA
Anjorin, A
Anney, R
Anttila, V
Arking, DE
Asherson, P
Azevedo, MH
Backlund, L
Badner, JA
Bailey, AJ
Banaschewski, T
Barchas, JD
Barnes, MR
Barrett, TB
Bass, N
Battaglia, A
Bauer, M
Bayes, M
Bellivier, F
Bergen, SE
Berrettini, W
Betancur, C
Bettecken, T
Biederman, J
Binder, EB
Black, DW
Blackwood, DHR
Bloss, CS
Boehnke, M
Boomsma, DI
Breen, G
Breuer, R
Bruggeman, R
Cormican, P
Buccola, NG
Buitelaar, JK
Bunney, WE
Buxbaum, JD
Byerley, WF
Byrne, EM
Caesar, S
Cahn, W
Cantor, RM
Casas, M
Chakravarti, A
Chambert, K
Choudhury, K
Cichon, S
Cloninger, CR
Collier, DA
Cook, EH
Coon, H
Cormand, B
Corvin, A
Coryell, WH
Craig, DW
Craig, IW
Crosbie, J
Cuccaro, ML
Curtis, D
Czamara, D
Datta, S
Dawson, G
Day, R
De Geus, EJ
Degenhardt, F
Djurovic, S
Donohoe, GJ
Doyle, AE
Duan, JB
Dudbridge, F
Duketis, E
Ebstein, RP
Edenberg, HJ
Elia, J
Ennis, S
Etain, B
Fanous, A
Farmer, AE
Ferrier, IN
Flickinger, M
Fombonne, E
Foroud, T
Frank, J
Franke, B
Fraser, C
Freedman, R
Freimer, NB
Freitag, CM
Friedl, M
Frisen, L
Gallagher, L
Gejman, PV
Georgieva, L
Gershon, ES
Geschwind, DH
Giegling, I
Gill, M
Gordon, SD
Gordon-Smith, K
Green, EK
Greenwood, TA
Grice, DE
Gross, M
Grozeva, D
Guan, WH
Gurling, H
De Haan, L
Haines, JL
Hakonarson, H
Hallmayer, J
Hamilton, SP
Hamshere, ML
Hansen, TF
Hartmann, AM
Hautzinger, M
Heath, AC
Henders, AK
Herms, S
Hickie, IB
Hipolito, M
Hoefels, S
Holmans, PA
Holsboer, F
Hoogendijk, WJ
Hottenga, JJ
Hultman, CM
Hus, V
Ingason, A
Ising, M
Jamain, S
Jones, EG
Jones, I
Jones, L
Tzeng, JY
Kahler, AK
Kahn, RS
Kandaswamy, R
Keller, MC
Kennedy, JL
Kenny, E
Kent, L
Kim, Y
Kirov, GK
Klauck, SM
Klei, L
Knowles, JA
Kohli, MA
Koller, DL
Konte, B
Korszun, A
Krabbendam, L
Krasucki, R
Kuntsi, J
Kwan, P
Landen, M
Langstrom, N
Lathrop, M
Lawrence, J
Lawson, WB
Leboyer, M
Ledbetter, DH
Lee, PH
Lencz, T
Lesch, KP
Levinson, DF
Lewis, CM
Li, J
Lichtenstein, P
Lieberman, JA
Lin, DY
Linszen, DH
Liu, CY
Lohoff, FW
Loo, SK
Lord, C
Lowe, JK
Lucae, S
MacIntyre, DJ
Madden, PAF
Maestrini, E
Magnusson, PKE
Mahon, PB
Maier, W
Malhotra, AK
Mane, SM
Martin, CL
Martin, NG
Mattheisen, M
Matthews, K
Mattingsdal, M
McCarroll, SA
McGhee, KA
McGough, JJ
McGrath, PJ
McGuffin, P
McInnis, MG
McIntosh, A
McKinney, R
McLean, AW
McMahon, FJ
McMahon, WM
McQuillin, A
Medeiros, H
Medland, SE
Meier, S
Melle, I
Meng, F
Meyer, J
Middeldorp, CM
Middleton, L
Milanova, V
Miranda, A
Monaco, AP
Montgomery, GW
Moran, JL
Moreno-De-Luca, D
Morken, G
Morris, DW
Morrow, EM
Moskvina, V
Muglia, P
Muhleisen, TW
Muir, WJ
Muller-Myhsok, B
Murtha, M
Myers, RM
Myin-Germeys, I
Neale, MC
Nelson, SF
Nievergelt, CM
Nikolov, I
Nimgaonkar, V
Nolen, WA
Nothen, MM
Nurnberger, JI
Nwulia, EA
Nyholt, DR
O'Dushlaine, C
Oades, RD
Olincy, A
Oliveira, G
Olsen, L
Ophoff, RA
Osby, U
Owen, MJ
Palotie, A
Parr, JR
Paterson, AD
Pato, CN
Pato, MT
Penninx, BW
Pergadia, ML
Pericak-Vance, MA
Pickard, BS
Pimm, J
Piven, J
Posthuma, D
Potash, JB
Poustka, F
Propping, P
Puri, V
Quested, DJ
Quinn, EM
Ramos-Quiroga, JA
Rasmussen, HB
Raychaudhuri, S
Rehnstrom, K
Reif, A
Ribases, M
Rice, JP
Rietschel, M
Roeder, K
Roeyers, H
Rossin, L
Rothenberger, A
Rouleau, G
Ruderfer, D
Rujescu, D
Sanders, AR
Sanders, SJ
Santangelo, SL
Sergeant, JA
Schachar, R
Schalling, M
Schatzberg, AF
Scheftner, WA
Schellenberg, GD
Scherer, SW
Schork, NJ
Schulze, TG
Schumacher, J
Schwarz, M
Scolnick, E
Scott, LJ
Shi, JX
Shilling, PD
Shyn, SI
Silverman, JM
Slager, SL
Smalley, SL
Smit, JH
Smith, EN
Sonuga-Barke, EJS
St Clair, D
State, M
Steffens, M
Steinhausen, HC
Strauss, JS
Strohmaier, J
Stroup, TS
Sutcliffe, JS
Szatmari, P
Szelinger, S
Thirumalai, S
Thompson, RC
Todorov, AA
Tozzi, F
Treutlein, J
Uhr, M
van den Oord, EJCG
Van Grootheest, G
Van Os, J
Vicente, AM
Vieland, VJ
Vincent, JB
Visscher, PM
Walsh, CA
Wassink, TH
Watson, SJ
Weissman, MM
Werge, T
Wienker, TF
Wijsman, EM
Willemsen, G
Williams, N
Willsey, AJ
Witt, SH
Xu, W
Young, AH
Yu, TW
Zammit, S
Zandi, PP
Zhang, P
Zitman, FG
Zollner, S
Devlin, B
Kelsoe, JR
Sklar, P
Daly, MJ
O'Donovan, MC
Craddock, N
Sullivan, PF
Smoller, JW
Kendler, KS
Wray, NR
AF Lee, S. Hong
Ripke, Stephan
Neale, Benjamin M.
Faraone, Stephen V.
Purcell, Shaun M.
Perlis, Roy H.
Mowry, Bryan J.
Thapar, Anita
Goddard, Michael E.
Witte, John S.
Absher, Devin
Agartz, Ingrid
Akil, Huda
Amin, Farooq
Andreassen, Ole A.
Anjorin, Adebayo
Anney, Richard
Anttila, Verneri
Arking, Dan E.
Asherson, Philip
Azevedo, Maria H.
Backlund, Lena
Badner, Judith A.
Bailey, Anthony J.
Banaschewski, Tobias
Barchas, Jack D.
Barnes, Michael R.
Barrett, Thomas B.
Bass, Nicholas
Battaglia, Agatino
Bauer, Michael
Bayes, Monica
Bellivier, Frank
Bergen, Sarah E.
Berrettini, Wade
Betancur, Catalina
Bettecken, Thomas
Biederman, Joseph
Binder, Elisabeth B.
Black, Donald W.
Blackwood, Douglas H. R.
Bloss, Cinnamon S.
Boehnke, Michael
Boomsma, Dorret I.
Breen, Gerome
Breuer, Rene
Bruggeman, Richard
Cormican, Paul
Buccola, Nancy G.
Buitelaar, Jan K.
Bunney, William E.
Buxbaum, Joseph D.
Byerley, William F.
Byrne, Enda M.
Caesar, Sian
Cahn, Wiepke
Cantor, Rita M.
Casas, Miguel
Chakravarti, Aravinda
Chambert, Kimberly
Choudhury, Khalid
Cichon, Sven
Cloninger, C. Robert
Collier, David A.
Cook, Edwin H.
Coon, Hilary
Cormand, Bru
Corvin, Aiden
Coryell, William H.
Craig, David W.
Craig, Ian W.
Crosbie, Jennifer
Cuccaro, Michael L.
Curtis, David
Czamara, Darina
Datta, Susmita
Dawson, Geraldine
Day, Richard
De Geus, Eco J.
Degenhardt, Franziska
Djurovic, Srdjan
Donohoe, Gary J.
Doyle, Alysa E.
Duan, Jubao
Dudbridge, Frank
Duketis, Eftichia
Ebstein, Richard P.
Edenberg, Howard J.
Elia, Josephine
Ennis, Sean
Etain, Bruno
Fanous, Ayman
Farmer, Anne E.
Ferrier, I. Nicol
Flickinger, Matthew
Fombonne, Eric
Foroud, Tatiana
Frank, Josef
Franke, Barbara
Fraser, Christine
Freedman, Robert
Freimer, Nelson B.
Freitag, Christine M.
Friedl, Marion
Frisen, Louise
Gallagher, Louise
Gejman, Pablo V.
Georgieva, Lyudmila
Gershon, Elliot S.
Geschwind, Daniel H.
Giegling, Ina
Gill, Michael
Gordon, Scott D.
Gordon-Smith, Katherine
Green, Elaine K.
Greenwood, Tiffany A.
Grice, Dorothy E.
Gross, Magdalena
Grozeva, Detelina
Guan, Weihua
Gurling, Hugh
De Haan, Lieuwe
Haines, Jonathan L.
Hakonarson, Hakon
Hallmayer, Joachim
Hamilton, Steven P.
Hamshere, Marian L.
Hansen, Thomas F.
Hartmann, Annette M.
Hautzinger, Martin
Heath, Andrew C.
Henders, Anjali K.
Herms, Stefan
Hickie, Ian B.
Hipolito, Maria
Hoefels, Susanne
Holmans, Peter A.
Holsboer, Florian
Hoogendijk, Witte J.
Hottenga, Jouke-Jan
Hultman, Christina M.
Hus, Vanessa
Ingason, Andres
Ising, Marcus
Jamain, Stephane
Jones, Edward G.
Jones, Ian
Jones, Lisa
Tzeng, Jung-Ying
Kaehler, Anna K.
Kahn, Rene S.
Kandaswamy, Radhika
Keller, Matthew C.
Kennedy, James L.
Kenny, Elaine
Kent, Lindsey
Kim, Yunjung
Kirov, George K.
Klauck, Sabine M.
Klei, Lambertus
Knowles, James A.
Kohli, Martin A.
Koller, Daniel L.
Konte, Bettina
Korszun, Ania
Krabbendam, Lydia
Krasucki, Robert
Kuntsi, Jonna
Kwan, Phoenix
Landen, Mikael
Langstrom, Niklas
Lathrop, Mark
Lawrence, Jacob
Lawson, William B.
Leboyer, Marion
Ledbetter, David H.
Lee, Phil H.
Lencz, Todd
Lesch, Klaus-Peter
Levinson, Douglas F.
Lewis, Cathryn M.
Li, Jun
Lichtenstein, Paul
Lieberman, Jeffrey A.
Lin, Dan-Yu
Linszen, Don H.
Liu, Chunyu
Lohoff, Falk W.
Loo, Sandra K.
Lord, Catherine
Lowe, Jennifer K.
Lucae, Susanne
MacIntyre, Donald J.
Madden, Pamela A. F.
Maestrini, Elena
Magnusson, Patrik K. E.
Mahon, Pamela B.
Maier, Wolfgang
Malhotra, Anil K.
Mane, Shrikant M.
Martin, Christa L.
Martin, Nicholas G.
Mattheisen, Manuel
Matthews, Keith
Mattingsdal, Morten
McCarroll, Steven A.
McGhee, Kevin A.
McGough, James J.
McGrath, Patrick J.
McGuffin, Peter
McInnis, Melvin G.
McIntosh, Andrew
McKinney, Rebecca
McLean, Alan W.
McMahon, Francis J.
McMahon, William M.
McQuillin, Andrew
Medeiros, Helena
Medland, Sarah E.
Meier, Sandra
Melle, Ingrid
Meng, Fan
Meyer, Jobst
Middeldorp, Christel M.
Middleton, Lefkos
Milanova, Vihra
Miranda, Ana
Monaco, Anthony P.
Montgomery, Grant W.
Moran, Jennifer L.
Moreno-De-Luca, Daniel
Morken, Gunnar
Morris, Derek W.
Morrow, Eric M.
Moskvina, Valentina
Muglia, Pierandrea
Muehleisen, Thomas W.
Muir, Walter J.
Mueller-Myhsok, Bertram
Murtha, Michael
Myers, Richard M.
Myin-Germeys, Inez
Neale, Michael C.
Nelson, Stan F.
Nievergelt, Caroline M.
Nikolov, Ivan
Nimgaonkar, Vishwajit
Nolen, Willem A.
Noethen, Markus M.
Nurnberger, John I.
Nwulia, Evaristus A.
Nyholt, Dale R.
O'Dushlaine, Colm
Oades, Robert D.
Olincy, Ann
Oliveira, Guiomar
Olsen, Line
Ophoff, Roel A.
Osby, Urban
Owen, Michael J.
Palotie, Aarno
Parr, Jeremy R.
Paterson, Andrew D.
Pato, Carlos N.
Pato, Michele T.
Penninx, Brenda W.
Pergadia, Michele L.
Pericak-Vance, Margaret A.
Pickard, Benjamin S.
Pimm, Jonathan
Piven, Joseph
Posthuma, Danielle
Potash, James B.
Poustka, Fritz
Propping, Peter
Puri, Vinay
Quested, Digby J.
Quinn, Emma M.
Antoni Ramos-Quiroga, Josep
Rasmussen, Henrik B.
Raychaudhuri, Soumya
Rehnstroem, Karola
Reif, Andreas
Ribases, Marta
Rice, John P.
Rietschel, Marcella
Roeder, Kathryn
Roeyers, Herbert
Rossin, Lizzy
Rothenberger, Aribert
Rouleau, Guy
Ruderfer, Douglas
Rujescu, Dan
Sanders, Alan R.
Sanders, Stephan J.
Santangelo, Susan L.
Sergeant, Joseph A.
Schachar, Russell
Schalling, Martin
Schatzberg, Alan F.
Scheftner, William A.
Schellenberg, Gerard D.
Scherer, Stephen W.
Schork, Nicholas J.
Schulze, Thomas G.
Schumacher, Johannes
Schwarz, Markus
Scolnick, Edward
Scott, Laura J.
Shi, Jianxin
Shilling, Paul D.
Shyn, Stanley I.
Silverman, Jeremy M.
Slager, Susan L.
Smalley, Susan L.
Smit, Johannes H.
Smith, Erin N.
Sonuga-Barke, Edmund J. S.
St Clair, David
State, Matthew
Steffens, Michael
Steinhausen, Hans-Christoph
Strauss, John S.
Strohmaier, Jana
Stroup, T. Scott
Sutcliffe, James S.
Szatmari, Peter
Szelinger, Szabocls
Thirumalai, Srinivasa
Thompson, Robert C.
Todorov, Alexandre A.
Tozzi, Federica
Treutlein, Jens
Uhr, Manfred
van den Oord, Edwin J. C. G.
Van Grootheest, Gerard
Van Os, Jim
Vicente, Astrid M.
Vieland, Veronica J.
Vincent, John B.
Visscher, Peter M.
Walsh, Christopher A.
Wassink, Thomas H.
Watson, Stanley J.
Weissman, Myrna M.
Werge, Thomas
Wienker, Thomas F.
Wijsman, Ellen M.
Willemsen, Gonneke
Williams, Nigel
Willsey, A. Jeremy
Witt, Stephanie H.
Xu, Wei
Young, Allan H.
Yu, Timothy W.
Zammit, Stanley
Zandi, Peter P.
Zhang, Peng
Zitman, Frans G.
Zoellner, Sebastian
Devlin, Bernie
Kelsoe, John R.
Sklar, Pamela
Daly, Mark J.
O'Donovan, Michael C.
Craddock, Nicholas
Sullivan, Patrick F.
Smoller, Jordan W.
Kendler, Kenneth S.
Wray, Naomi R.
CA Cross-Disorder Grp Psychiat Genomi
Int Inflammatory Bowel Dis Genetic
TI Genetic relationship between five psychiatric disorders estimated from
genome-wide SNPs
SO NATURE GENETICS
LA English
DT Article
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY
DISORDER; AUTISM SPECTRUM DISORDERS; MAJOR DEPRESSIVE DISORDER; BIPOLAR
DISORDER; COMMON SNPS; CROHNS-DISEASE; SCHIZOPHRENIA; RISK; ASSOCIATION
AB Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 +/- 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 +/- 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 +/- 0.06 s.e.), and ADHD and major depressive disorder (0.32 +/- 0.07 s.e.), low between schizophrenia and ASD (0.16 +/- 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.
C1 [Lee, S. Hong; Mowry, Bryan J.; Byrne, Enda M.; Visscher, Peter M.; Wray, Naomi R.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.
[Ripke, Stephan; Neale, Benjamin M.; Purcell, Shaun M.; Anttila, Verneri; Raychaudhuri, Soumya; Daly, Mark J.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Ripke, Stephan; Neale, Benjamin M.; Purcell, Shaun M.; Anttila, Verneri; Raychaudhuri, Soumya; Daly, Mark J.] Harvard Univ, Sch Med, Boston, MA USA.
[Ripke, Stephan; Neale, Benjamin M.; Purcell, Shaun M.; Perlis, Roy H.; Bergen, Sarah E.; Chambert, Kimberly; McCarroll, Steven A.; Moran, Jennifer L.; O'Dushlaine, Colm; Raychaudhuri, Soumya; Rossin, Lizzy; Scolnick, Edward; Daly, Mark J.; Smoller, Jordan W.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, 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.
[Purcell, Shaun M.; Ruderfer, Douglas; Sklar, Pamela] Icahn Sch Med Mt Sinai, Dept Psychiat, Div Psychiat Genom, New York, NY USA.
[Perlis, Roy H.; Bergen, Sarah E.; Lee, Phil H.; Smoller, Jordan W.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Mowry, Bryan J.] Queensland Ctr Mental Hlth Res, Wacol, Qld, Australia.
[Thapar, Anita; Fraser, Christine; Georgieva, Lyudmila; Gordon-Smith, Katherine; Grozeva, Detelina; Hamshere, Marian L.; Holmans, Peter A.; Jones, Ian; Kirov, George K.; Moskvina, Valentina; Nikolov, Ivan; Owen, Michael J.; Williams, Nigel; Zammit, Stanley; O'Donovan, Michael C.; Craddock, Nicholas] Cardiff Univ, Sch Med, MRC, Ctr Neuropsychiat Genet & Genom, Cardiff CF10 3AX, S Glam, Wales.
[Thapar, Anita; Fraser, Christine; Georgieva, Lyudmila; Jones, Ian; Kirov, George K.; Nikolov, Ivan; Owen, Michael J.; Williams, Nigel; Zammit, Stanley; O'Donovan, Michael C.; Craddock, Nicholas] Cardiff Univ, Sch Med, Inst Psychol Med & Clin Neurosci, Cardiff CF10 3AX, S Glam, Wales.
[Goddard, Michael E.] Dept Environm & Primary Ind Victoria, Biosci Res Div, Melbourne, Vic, Australia.
[Goddard, Michael E.] Univ Melbourne, Fac Land & Environm, Melbourne, Vic, Australia.
[Witte, John S.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Absher, Devin; Myers, Richard M.] HudsonAlpha Inst Biotechnol, Huntsville, AL USA.
[Agartz, Ingrid; Andreassen, Ole A.; Djurovic, Srdjan; Mattingsdal, Morten; Melle, Ingrid] Univ Oslo, Inst Clin Med, KG Jebsen Ctr Psychosis Res, Oslo, Norway.
[Agartz, Ingrid] Diakonhjemmet Hosp, Dept Res, Oslo, Norway.
[Akil, Huda; Meng, Fan; Thompson, Robert C.; Watson, Stanley J.] Univ Michigan, Mol & Behav Neurosci Inst, Mol Psychiat Lab, Ann Arbor, MI 48109 USA.
[Amin, Farooq] Emory Univ, Atlanta Vet Affairs Med Ctr, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA.
[Andreassen, Ole A.; Melle, Ingrid] Oslo Univ Hosp, Div Mental Hlth & Addict, Oslo, Norway.
[Anjorin, Adebayo; Bass, Nicholas; Choudhury, Khalid; Gurling, Hugh; Kandaswamy, Radhika; Krasucki, Robert; Lawrence, Jacob; McQuillin, Andrew; Pimm, Jonathan; Puri, Vinay] UCL, Mental Hlth Sci Unit, London, England.
[Anney, Richard; Cormican, Paul; Corvin, Aiden; Donohoe, Gary J.; Gallagher, Louise; Gill, Michael; Kenny, Elaine; Morris, Derek W.; Quinn, Emma M.] Univ Dublin Trinity Coll, Dept Psychiat, Dublin 2, Ireland.
[Arking, Dan E.; Chakravarti, Aravinda] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA.
[Asherson, Philip; Breen, Gerome; Collier, David A.; Craig, Ian W.; Farmer, Anne E.; Kuntsi, Jonna; Lewis, Cathryn M.; McGuffin, Peter] Kings Coll London, Inst Psychiat, MRC, Social Genet & Dev Psychiat SGDP Ctr, London, England.
[Azevedo, Maria H.; Oliveira, Guiomar] Univ Coimbra, Fac Med, Coimbra, Portugal.
[Backlund, Lena; Frisen, Louise; Osby, Urban; Schalling, Martin] Karolinska Inst, Ctr Mol Med, Dept Mol Med & Surg, Stockholm, Sweden.
[Badner, Judith A.; Gershon, Elliot S.] Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA.
[Bailey, Anthony J.] Univ British Columbia, Dept Psychiat, Vancouver, BC, Canada.
[Banaschewski, Tobias] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Child & Adolescent Psychiat & Psychotherapy, Mannheim, Germany.
[Barchas, Jack D.] Cornell Univ, Weill Med Coll, Dept Psychiat, New York, NY 10021 USA.
[Barnes, Michael R.] GlaxoSmithKline, London, England.
[Barrett, Thomas B.] Portland VA Med Ctr, Portland, OR USA.
[Battaglia, Agatino] Stella Maris Inst Child & Adolescent Neuropsychia, Pisa, Italy.
[Bauer, Michael] Carl Gustav Carus Univ Hosp, Dept Psychiat & Psychotherapy, Dresden, Germany.
[Bayes, Monica] Parc Cient Barcelona, Ctr Nacl Anal Genom, Barcelona, Spain.
[Bellivier, Frank; Etain, Bruno; Jamain, Stephane; Leboyer, Marion] Hop Henri Mondor, INSERM, U955, F-94010 Creteil, France.
[Bellivier, Frank] Univ Paris 07, Paris, France.
[Bellivier, Frank] Grp Hosp St Louis, AP HP, Dept Psychiat, Paris, France.
[Bellivier, Frank; Etain, Bruno; Jamain, Stephane; Leboyer, Marion] Fdn FondaMental, ENBREC European Network Bipolar Res Expert Ctr Gr, Creteil, France.
[Bergen, Sarah E.; Hultman, Christina M.; Kaehler, Anna K.; Landen, Mikael; Langstrom, Niklas; Lichtenstein, Paul; Magnusson, Patrik K. E.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Berrettini, Wade; Elia, Josephine; Lohoff, Falk W.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
[Betancur, Catalina] INSERM, U952, Paris, France.
[Betancur, Catalina] CNRS, Unite Mixte Rech UMR 7224, Paris, France.
[Betancur, Catalina] Univ Paris 06, Paris, France.
[Bettecken, Thomas; Binder, Elisabeth B.; Czamara, Darina; Holsboer, Florian; Ising, Marcus; Kohli, Martin A.; Lucae, Susanne; Mueller-Myhsok, Bertram; Uhr, Manfred] Max Planck Inst Psychiat, D-80804 Munich, Germany.
[Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Programs Pediat Psychopharmacol & Adul, Boston, MA 02114 USA.
[Black, Donald W.; Coryell, William H.; Potash, James B.; Wassink, Thomas H.] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA.
[Blackwood, Douglas H. R.; MacIntyre, Donald J.; McGhee, Kevin A.; McIntosh, Andrew; McLean, Alan W.; Muir, Walter J.; Pickard, Benjamin S.] Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh, Midlothian, Scotland.
[Bloss, Cinnamon S.; Schork, Nicholas J.; Smith, Erin N.] Scripps Translat Sci Inst, La Jolla, CA USA.
[Bloss, Cinnamon S.] Scripps Hlth, La Jolla, CA USA.
[Boehnke, Michael; Flickinger, Matthew; Guan, Weihua; Kwan, Phoenix; Scott, Laura J.; Zhang, Peng; Zoellner, Sebastian] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.
[Boehnke, Michael; Flickinger, Matthew; Guan, Weihua; Kwan, Phoenix; Scott, Laura J.; Zhang, Peng; Zoellner, Sebastian] Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Boomsma, Dorret I.; De Geus, Eco J.; Hottenga, Jouke-Jan; Middeldorp, Christel M.; Willemsen, Gonneke] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.
[Boomsma, Dorret I.; De Geus, Eco J.; Penninx, Brenda W.; Smit, Johannes H.; Van Grootheest, Gerard; Willemsen, Gonneke] EMGO Inst Hlth & Care Res, Amsterdam, Netherlands.
[Boomsma, Dorret I.; De Geus, Eco J.; Hottenga, Jouke-Jan; Middeldorp, Christel M.; Penninx, Brenda W.] Neurosci Campus Amsterdam, Amsterdam, Netherlands.
[Breen, Gerome] Natl Inst Heath Res, Biomed Res Ctr Mental Hlth, London, England.
[Breen, Gerome] Maudsley Natl Hlth Serv NHS Trust, London, England.
[Breen, Gerome] Inst Psychiat, London, England.
[Breuer, Rene; Frank, Josef; Meier, Sandra; Rietschel, Marcella; Strohmaier, Jana; Treutlein, Jens; Witt, Stephanie H.] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, Mannheim, Germany.
[Bruggeman, Richard] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands.
[Buccola, Nancy G.] Louisiana State Univ, Sch Nursing, Hlth Sci Ctr, New Orleans, LA USA.
[Buitelaar, Jan K.; Franke, Barbara] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Cognit Neurosci, NL-6525 ED Nijmegen, Netherlands.
[Bunney, William E.] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA.
[Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Psychiat, Seaver Autism Ctr Res & Treatment, New York, NY USA.
[Byerley, William F.; Hamilton, Steven P.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Byerley, William F.] NCIRE Northern Calif Inst Q Res & Educ, San Francisco, CA USA.
[Caesar, Sian; Gordon-Smith, Katherine; Jones, Lisa] Univ Birmingham, Dept Psychiat, Birmingham, W Midlands, England.
[Cahn, Wiepke; Kahn, Rene S.] Univ Med Ctr, Rudolf Magnus Inst Neurosci, Dept Psychiat, Utrecht, Netherlands.
[Cantor, Rita M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Casas, Miguel; Antoni Ramos-Quiroga, Josep; Ribases, Marta] Hosp Univ Vall Hebron, CIBERSAM Ctr Invest Biomed Area Salud Mental, Dept Psychiat, Barcelona, Spain.
[Casas, Miguel; Antoni Ramos-Quiroga, Josep] Univ Autonoma Barcelona, Dept Psychiat & Legal Med, E-08193 Barcelona, Spain.
[Cichon, Sven; Degenhardt, Franziska; Herms, Stefan; Muehleisen, Thomas W.; Noethen, Markus M.] Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany.
[Cichon, Sven] Res Ctr Julich, Inst Neurosci & Med INM 1, Julich, Germany.
[Cichon, Sven; Degenhardt, Franziska; Mattheisen, Manuel; Muehleisen, Thomas W.; Noethen, Markus M.; Propping, Peter; Schumacher, Johannes] Univ Bonn, Inst Human Genet, Bonn, Germany.
[Cichon, Sven; Herms, Stefan] Univ Basel, Div Med Genet, Dept Biomed, Basel, Switzerland.
[Cloninger, C. Robert; Heath, Andrew C.; Madden, Pamela A. F.; Pergadia, Michele L.; Todorov, Alexandre A.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Cook, Edwin H.] Univ Illinois, Dept Psychiat, Inst Juvenile Res, Chicago, IL 60612 USA.
[Coon, Hilary; McMahon, William M.] Univ Utah, Dept Psychiat, Salt Lake City, UT USA.
[Cormand, Bru] Univ Barcelona, Fac Biol, Dept Genet, Barcelona, Spain.
[Cormand, Bru] Biomed Network Res Ctr Rare Dis CIBERER, Barcelona, Spain.
[Cormand, Bru] Univ Barcelona IBUB, Inst Biomed, Barcelona, Spain.
[Craig, David W.; Szelinger, Szabocls] Translat Genom Res Inst, Phoenix, AZ USA.
[Crosbie, Jennifer; Schachar, Russell] Univ Toronto, Hosp Sick Children, Neurosci & Mental Hlth Program, Toronto, ON M5G 1X8, Canada.
[Cuccaro, Michael L.; Pericak-Vance, Margaret A.] Univ Miami, John P Hussman Inst Human Genom, Miami, FL USA.
[Curtis, David] Univ London, East London NHS Fdn Trust, London, England.
[Czamara, Darina; Mueller-Myhsok, Bertram] Munich Cluster Syst Neurol SyNergy, Munich, Germany.
[Datta, Susmita] UCL, Genet Inst, London, England.
[Dawson, Geraldine] Autism Speaks, New York, NY USA.
[Dawson, Geraldine] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
[Dawson, Geraldine; Piven, Joseph] Univ N Carolina, Carolina Inst Dev Disabil, Chapel Hill, NC USA.
[Day, Richard; Matthews, Keith] Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Div Neurosci, Dundee DD1 9SY, Scotland.
[Djurovic, Srdjan] Oslo Univ Hosp, Dept Med Genet, Oslo, Norway.
[Doyle, Alysa E.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Duan, Jubao; Gejman, Pablo V.; Sanders, Alan R.] NorthShore Univ Hlth Syst, Dept Psychiat & Behav Sci, Evanston, IL USA.
[Duan, Jubao; Gejman, Pablo V.; Sanders, Alan R.] Univ Chicago, Evanston, IL USA.
[Dudbridge, Frank] London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London WC1, England.
[Duketis, Eftichia; Freitag, Christine M.; Poustka, Fritz] Goethe Univ Frankfurt, Dept Child & Adolescent Psychiat Psychosomat & Ps, D-60054 Frankfurt, Germany.
[Ebstein, Richard P.] Natl Univ Singapore, Dept Psychol, Singapore 117548, Singapore.
[Edenberg, Howard J.] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA.
[Edenberg, Howard J.; Foroud, Tatiana; Koller, Daniel L.; Nurnberger, John I.] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA.
[Elia, Josephine] Univ Penn, AI Dupont Hosp Children, Philadelphia, PA 19104 USA.
[Ennis, Sean] Univ Coll Med Sci, Sch Med, Dublin, Ireland.
[Etain, Bruno; Jamain, Stephane; Leboyer, Marion] Univ Paris Est, Fac Med, Creteil, France.
[Etain, Bruno; Jamain, Stephane; Leboyer, Marion] Hop H Mondor A Chenevier, AP HP, Dept Psychiat, Creteil, France.
[Fanous, Ayman] Georgetown Univ, Sch Med, Dept Psychiat, Washington, DC USA.
[Fanous, Ayman; Neale, Michael C.; Kendler, Kenneth S.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA.
[Ferrier, I. Nicol; Parr, Jeremy R.; Young, Allan H.] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Fombonne, Eric] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA.
[Fombonne, Eric] Oregon Hlth & Sci Univ, Inst Dev & Disabil, Portland, OR 97201 USA.
[Freedman, Robert; Olincy, Ann] Univ Colorado Denver, Dept Psychiat, Aurora, CO USA.
[Freimer, Nelson B.; Loo, Sandra K.; Nelson, Stan F.; Ophoff, Roel A.; Smalley, Susan L.] Univ Calif Los Angeles, Dept Neurobehav Genet, Los Angeles, CA USA.
[Friedl, Marion; Giegling, Ina; Hartmann, Annette M.; Konte, Bettina; Rujescu, Dan] Univ Halle, Dept Psychiat, Halle, Germany.
[Geschwind, Daniel H.; Lowe, Jennifer K.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA.
[Geschwind, Daniel H.; Lowe, Jennifer K.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst, Ctr Autism Res & Treatment, Los Angeles, CA 90095 USA.
[Gordon, Scott D.; Henders, Anjali K.; Martin, Nicholas G.; Medland, Sarah E.; Montgomery, Grant W.; Nyholt, Dale R.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Green, Elaine K.] Univ Plymouth, Dept Biomed & Biol Sci, Plymouth PL4 8AA, Devon, England.
[Greenwood, Tiffany A.; McKinney, Rebecca; Nievergelt, Caroline M.; Shilling, Paul D.; Kelsoe, John R.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
[Grice, Dorothy E.] Icahn Sch Med Mt Sinai, Div Tics OCD & Related Disorders, New York, NY USA.
[Grice, Dorothy E.; Silverman, Jeremy M.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY USA.
[Gross, Magdalena; Hoefels, Susanne; Maier, Wolfgang] Univ Bonn, Dept Psychiat, Bonn, Germany.
[Guan, Weihua] Univ Minnesota, Div Biostat, Minneapolis, MN USA.
[De Haan, Lieuwe] Univ Amsterdam, Acad Med Ctr, Dept Psychiat, NL-1012 WX Amsterdam, Netherlands.
[Haines, Jonathan L.] Vanderbilt Univ, Med Ctr, Ctr Human Genet Res, Nashville, TN USA.
[Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Div Human Genet, Philadelphia, PA 19104 USA.
[Hakonarson, Hakon] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA.
[Hallmayer, Joachim] Stanford Univ, Sch Med, Dept Psychiat, Stanford, CA 94305 USA.
[Hamshere, Marian L.; Holmans, Peter A.; Moskvina, Valentina] Cardiff Univ, Biostat & Bioinformat Unit, Cardiff, S Glam, Wales.
[Hansen, Thomas F.; Ingason, Andres; Olsen, Line; Rasmussen, Henrik B.; Werge, Thomas] Copenhagen Univ Hosp, Inst Biol Psychiat, Roskilde, Denmark.
[Hansen, Thomas F.; Ingason, Andres; Mattheisen, Manuel; Olsen, Line; Rasmussen, Henrik B.; Werge, Thomas] iPSYCH, Lundbeck Initiat Integrat Psychiat Res, Roskilde, Denmark.
[Hautzinger, Martin] Univ Tubingen, Dept Clin & Dev Psychol, Tubingen, Germany.
[Hickie, Ian B.] Univ Sydney, Brain & Mind Res Inst, Sydney, NSW 2006, Australia.
[Hipolito, Maria; Lawson, William B.; Nwulia, Evaristus A.] Howard Univ, Coll Med, Dept Psychiat & Behav Sci, Washington, DC USA.
[Hoogendijk, Witte J.] Erasmus MC, Dept Psychiat, Rotterdam, Netherlands.
[Hus, Vanessa] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA.
[Jones, Edward G.] Univ Calif Davis, Ctr Neurosci, Davis, CA 95616 USA.
[Tzeng, Jung-Ying] N Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC 27695 USA.
[Keller, Matthew C.] Univ Colorado, Dept Psychol, Boulder, CO 80309 USA.
[Kennedy, James L.] Ctr Addict & Mental Hlth, Psychiat Neurogenet Sect, Toronto, ON, Canada.
[Kent, Lindsey] Univ St Andrews, Sch Med, St Andrews, Fife, Scotland.
[Kim, Yunjung; Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Klauck, Sabine M.] German Canc Res Ctr, Div Mol Genome Anal, Heidelberg, Germany.
[Klei, Lambertus; Devlin, Bernie] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA.
[Knowles, James A.; Medeiros, Helena; Pato, Carlos N.; Pato, Michele T.] Univ So Calif, Keck Sch Med, Dept Psychiat, Zilkha Neurogenet Inst, Los Angeles, CA 90033 USA.
[Korszun, Ania] Queen Mary Univ London, Wolfson Inst Preventit Med, London, England.
[Krabbendam, Lydia; Myin-Germeys, Inez; Van Os, Jim] Maastricht Univ, Med Ctr, South Limburg Mental Hlth Res & Teaching Network, Dept Psychiat & Neuropsychol, Maastricht, Netherlands.
[Landen, Mikael] Univ Gothenburg, Inst Neurosci & Physiol, Gothenburg, Sweden.
[Lathrop, Mark] Ctr Natl Genotypage, Evry, France.
[Ledbetter, David H.; Martin, Christa L.] Geisinger Hlth Syst, Autism & Dev Med Inst, Danville, PA USA.
[Lencz, Todd; Malhotra, Anil K.] Long Isl Jewish Hlth Syst, Zucker Hillside Hosp, Div North Shore, Dept Psychiat,Div Res, Glen Oaks, NY USA.
[Lencz, Todd; Malhotra, Anil K.] Feinstein Inst Med Res, Ctr Psychiat Neurosci, Manhasset, NY USA.
[Lencz, Todd; Malhotra, Anil K.] Yeshiva Univ, Albert Einstein Coll Med, Dept Psychiat & Behav Sci, Bronx, NY USA.
[Lesch, Klaus-Peter] Univ Wurzburg, ADHD Clin Res Unit, Dept Psychiat Psychosomat & Psychotherapy, Div Mol Psychiat, D-97070 Wurzburg, Germany.
[Lesch, Klaus-Peter] Maastricht Univ, Sch Mental Hlth & Neurosci MHENS, Dept Psychiat & Psychol, Maastricht, Netherlands.
[Levinson, Douglas F.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
[Li, Jun] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
[Lieberman, Jeffrey A.; McGrath, Patrick J.] Columbia Univ, New York State Psychiat Inst, New York, NY USA.
[Lin, Dan-Yu] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA.
[Linszen, Don H.] Univ Amsterdam, Acad Med Ctr, Dept Psychiat, NL-1105 AZ Amsterdam, Netherlands.
[Liu, Chunyu] Univ Illinois, Dept Psychiat, Inst Human Genet, Chicago, IL 60612 USA.
[Loo, Sandra K.; Smalley, Susan L.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA.
[Lord, Catherine] Weill Cornell Med Coll, Ctr Autism & Developing Brain, White Plains, NY USA.
[Maestrini, Elena] Univ Bologna, Dept Pharm & Biotechnol, Bologna, Italy.
[Mahon, Pamela B.; Schulze, Thomas G.] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD USA.
[Mane, Shrikant M.] Yale Ctr Genome Anal, Orange, CT USA.
[Mattheisen, Manuel] Aarhus Univ, Dept Biomed, Aarhus, Denmark.
[Mattheisen, Manuel] Univ Bonn, Dept Genom Math, Bonn, Germany.
[Mattingsdal, Morten] Sorlandet Hosp, Kristiansand, Norway.
[McGough, James J.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst, Los Angeles, CA 90095 USA.
[McInnis, Melvin G.; Zhang, Peng; Zoellner, Sebastian] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA.
[McIntosh, Andrew; McLean, Alan W.; Muir, Walter J.; Pickard, Benjamin S.] Univ Edinburgh, Mol Med Ctr, Edinburgh, Midlothian, Scotland.
[McMahon, Francis J.] NIMH, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Meyer, Jobst] Univ Trier, Dept Neurobehav Genet, Trier, Germany.
[Middleton, Lefkos] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England.
[Milanova, Vihra] Alexander Univ Hosp, Psychiat Clin 1, Dept Psychiat, Sofia, Bulgaria.
[Miranda, Ana] Univ Valencia, Dept Dev & Educ Psychol, Valencia, Spain.
[Monaco, Anthony P.] Univ Oxford, Ctr Human Genet, Wellcome Trust, Oxford, England.
[Monaco, Anthony P.] Tufts Univ, Off President, Medford, MA 02155 USA.
[Moreno-De-Luca, Daniel; Sanders, Stephan J.; State, Matthew] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA.
[Morken, Gunnar] St Olavs Hosp, Dept Psychiat, Trondheim, Norway.
[Morken, Gunnar] Norwegian Univ Sci & Technol, Dept Neurosci, N-7034 Trondheim, Norway.
[Morrow, Eric M.] Brown Univ, Dept Mol Biol Cell Biol & Biochem, Providence, RI 02912 USA.
[Morrow, Eric M.] Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA.
[Muglia, Pierandrea; Tozzi, Federica] GlaxoSmithKline Res & Dev Ltd, Neurosci Ctr Excellence Drug Discovery, Verona, Italy.
[Muehleisen, Thomas W.] Univ Bonn, Life & Brain Ctr, Bonn, Germany.
[Murtha, Michael; Sanders, Stephan J.; State, Matthew; Willsey, A. Jeremy] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA.
[Nimgaonkar, Vishwajit] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA.
[Nimgaonkar, Vishwajit] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA.
[Nolen, Willem A.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, NL-9713 AV Groningen, Netherlands.
[Nurnberger, John I.] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA.
[Oades, Robert D.] Univ Duisburg Essen, Clin Child & Adolescent Psychiat & Psychotherapy, Essen, Germany.
[Oliveira, Guiomar] Ctr Hosp Coimbra, Pediat Hosp, Res & Clin Training Dept, Coimbra, Portugal.
[Oliveira, Guiomar] Univ Coimbra, Coimbra, Portugal.
[Ophoff, Roel A.] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA.
[Ophoff, Roel A.] Univ Med Ctr Utrecht, Dept Psychiat, Utrecht, Netherlands.
[Palotie, Aarno; Rehnstroem, Karola] Sanger Inst, Cambridge, England.
[Paterson, Andrew D.] Hosp Sick Children, Program Genet & Genom Biol, Toronto, ON M5G 1X8, Canada.
[Paterson, Andrew D.; Xu, Wei] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Penninx, Brenda W.; Smit, Johannes H.; Van Grootheest, Gerard] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands.
[Posthuma, Danielle] Vrije Univ Amsterdam Med Ctr, Dept Funct Genom, Amsterdam, Netherlands.
[Posthuma, Danielle] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Amsterdam, Netherlands.
[Posthuma, Danielle] Erasmus Univ, Med Ctr, Dept Child & Adolescent Psychiat, Rotterdam, Netherlands.
[Quested, Digby J.] Univ Oxford, Acad Dept Psychiat, Oxford, England.
[Reif, Andreas] Univ Wurzburg, Dept Psychiat, Wurzburg, Germany.
[Ribases, Marta] Vall dHebron Res Inst, Psychiat Genet Unit, Barcelona, Spain.
[Rice, John P.] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA.
[Roeder, Kathryn] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA.
[Roeyers, Herbert; Sonuga-Barke, Edmund J. S.] Univ Ghent, Dept Expt Clin & Hlth Psychol, B-9000 Ghent, Belgium.
[Rothenberger, Aribert] Univ Med Gottingen, Gottingen, Germany.
[Rouleau, Guy] McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ, Canada.
[Sanders, Stephan J.; State, Matthew; Willsey, A. Jeremy] Yale Univ, Dept Genet, New Haven, CT USA.
[Sanders, Stephan J.] Yale Univ, Program Neurogenet, New Haven, CT USA.
[Santangelo, Susan L.] Maine Med Ctr, Dept Psychiat, Portland, ME 04102 USA.
[Santangelo, Susan L.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Sergeant, Joseph A.] Vrije Univ Amsterdam, Dept Clin Neuropsychol, Amsterdam, Netherlands.
[Schatzberg, Alan F.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA.
[Scheftner, William A.] Rush Univ, Med Ctr, Rush Ambulatory Behav Hlth, Chicago, IL 60612 USA.
[Schellenberg, Gerard D.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA.
[Scherer, Stephen W.] Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 1X8, Canada.
[Schork, Nicholas J.; Smith, Erin N.] Scripps Res Inst, La Jolla, CA 92037 USA.
[Schulze, Thomas G.] Univ Gottingen, Dept Psychiat & Psychotherapy, D-37073 Gottingen, Germany.
[Schwarz, Markus] Psychiat Ctr Nordbaden, Wiesloch, Germany.
[Shi, Jianxin] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Shyn, Stanley I.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Slager, Susan L.] Mayo Clin, Rochester, MN USA.
[Sonuga-Barke, Edmund J. S.] Univ Southampton, Dev Brain & Behav Lab, Acad Unit Psychol, Southampton, Hants, England.
[St Clair, David] Univ Aberdeen, Inst Med Sci, Aberdeen, Scotland.
[Steffens, Michael] Fed Inst Drugs & Med Devices BfArM, Res Dept, Bonn, Germany.
[Steinhausen, Hans-Christoph] Aalborg Univ Hosp, Res Unit Child & Adolescent Psychiat, Aalborg, Denmark.
[Steinhausen, Hans-Christoph] Univ Basel, Basel, Switzerland.
[Steinhausen, Hans-Christoph] Univ Zurich, Dept Child & Adolescent Psychiat, Zurich, Switzerland.
[Strauss, John S.; Vincent, John B.] Ctr Addict & Mental Hlth, Mol Neuropsychiat & Dev Lab, Toronto, ON, Canada.
[Stroup, T. Scott] Columbia Univ, Dept Psychiat, New York, NY USA.
[Sutcliffe, James S.] Vanderbilt Univ, Vanderbilt Brain Inst, Nashville, TN 37235 USA.
[Szatmari, Peter] Univ Toronto, Dept Psychiat, Toronto, ON, Canada.
[Szatmari, Peter] Hosp Sick Children, Neurosci & Mental Hlth Program, Toronto, ON M5G 1X8, Canada.
[Szatmari, Peter] Ctr Addict & Mental Hlth, Toronto, ON, Canada.
[Thirumalai, Srinivasa] Oxford Hlth NHS Fdn Trust, Marlborough House Secure Unit, Milton Keynes, Bucks, England.
[van den Oord, Edwin J. C. G.] Virginia Commonwealth Univ, Ctr Biomarker Res & Personalized Med, Richmond, VA USA.
[Vicente, Astrid M.] Inst Nacl Saude Dr Ricardo Jorge, Lisbon, Portugal.
[Vicente, Astrid M.] BioFIG Ctr Biodivers Funct & Integrat Genom, Lisbon, Portugal.
[Vicente, Astrid M.] Inst Gulbenkian Ciencias, Lisbon, Portugal.
[Vieland, Veronica J.] Nationwide Childrens Hosp, Battelle Ctr Math Med, Columbus, OH USA.
[Visscher, Peter M.] Univ Queensland, Diamantina Inst, Brisbane, Qld, Australia.
[Walsh, Christopher A.] Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA.
[Walsh, Christopher A.] Childrens Hosp, Div Genet, Boston, MA 02115 USA.
[Walsh, Christopher A.] Harvard Univ, Sch Med, Dept Neurol, Ctr Life Sci, Boston, MA 02115 USA.
[Walsh, Christopher A.] Harvard Univ, Sch Med, Dept Pediat, Ctr Life Sci, Boston, MA 02115 USA.
[Weissman, Myrna M.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA.
[Werge, Thomas] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
[Wienker, Thomas F.] Univ Bonn, Inst Med Biometry, Bonn, Germany.
[Wijsman, Ellen M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Wijsman, Ellen M.] Univ Washington, Dept Med, Seattle, WA USA.
[Young, Allan H.] Kings Coll London, Inst Psychiat, Ctr Affect Disorders, London, England.
[Yu, Timothy W.] Harvard Univ, Childrens Hosp Boston, Sch Med, Div Genet, Boston, MA USA.
[Zandi, Peter P.] Johns Hopkins Univ, Dept Mental Hlth, Baltimore, MD USA.
[Zitman, Frans G.] Leiden Univ, Med Ctr, Dept Psychiat, Leiden, Netherlands.
[Kelsoe, John R.] Vet Affairs San Diego Healthcare Syst, Special Treatment & Evaluat Program, Dept Psychiat, San Diego, CA USA.
[Kendler, Kenneth S.] Virginia Commonwealth Univ, Dept Human & Mol Genet, Richmond, VA USA.
[Kendler, Kenneth S.] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA.
RP Wray, NR (reprint author), Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.
EM naomi.wray@uq.edu.au
RI van Grootheest, Gerard/C-6942-2014; Kahler, Anna/J-2874-2012; Franke,
Barbara/D-4836-2009; Nolen, Willem/E-9006-2014; Morrow,
Eric/J-2767-2013; McGuffin, Peter/A-1565-2012; Sonuga-Barke,
Edmund/D-9137-2011; McIntosh, Andrew/B-9379-2008; Kuntsi,
Jonna/G-9750-2011; Scherer, Stephen /B-3785-2013; Cichon,
Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Herms, Stefan/J-1949-2014;
Stroup, Thomas/F-9188-2014; Magnusson, Patrik/C-4458-2017; Lesch,
Klaus-Peter/J-4906-2013; Vicente, Astrid/F-8692-2014; Miranda,
Ana/G-8619-2015; Cormand, Bru/H-5338-2015; Montgomery,
Grant/B-7148-2008; Zhang, Peng/N-2920-2014; Mattheisen,
Manuel/B-4949-2012; Paterson, Andrew/A-4088-2011; Melle, Ingrid
/B-4858-2011; Schumacher, Johannes/F-4970-2015; Ruderfer,
Douglas/M-5795-2016; Lohoff, Falk/M-7951-2016; Lencz, Todd/J-3418-2014;
BELLIVIER, FRANK/H-5197-2012; McQuillin, Andrew/C-1623-2008; Franke,
Andre/B-2151-2010; Nyholt, Dale/C-8384-2013; Monaco,
Anthony/A-4495-2010; Bailey, Anthony/J-2860-2014; Liu,
Chang/B-7249-2009; Thompson, Richard/J-8879-2014; Binder,
Elisabeth/K-8905-2014; Myin-Germeys, Inez /L-5106-2014; Lee, Sang
Hong/A-2569-2011; Breen, Gerome/A-5540-2010; Hansen, Thomas/O-5965-2014;
Wray, Naomi/C-8639-2015; Holmans, Peter/F-4518-2015; Sutcliffe,
James/C-1348-2012
OI van Grootheest, Gerard/0000-0003-4350-6661; Franke,
Barbara/0000-0003-4375-6572; McGuffin, Peter/0000-0002-9888-2907;
McIntosh, Andrew/0000-0002-0198-4588; Scherer, Stephen
/0000-0002-8326-1999; Cichon, Sven/0000-0002-9475-086X; Cichon,
Sven/0000-0002-9475-086X; Andreassen, Ole A./0000-0002-4461-3568;
Oliveira, Guiomar/0000-0002-7049-1277; Thapar,
Anita/0000-0002-3689-737X; Etain, Bruno/0000-0002-5377-1488; Visscher,
Peter/0000-0002-2143-8760; Gearry, Richard/0000-0002-2298-5141; Faraone,
Stephen/0000-0002-9217-3982; Edenberg, Howard/0000-0003-0344-9690;
Medland, Sarah/0000-0003-1382-380X; Pickard,
Benjamin/0000-0002-2374-6329; Steffens, Michael/0000-0002-6445-8593; de
Geus, Eco/0000-0001-6022-2666; Martin, Nicholas/0000-0003-4069-8020;
Betancur, Catalina/0000-0002-3327-4804; Yu, Timothy/0000-0003-2988-7701;
Buxbaum, Joseph/0000-0001-8898-8313; Bruggeman,
Richard/0000-0002-3238-8471; Weissman, Myrna/0000-0003-3490-3075;
Palmieri, Orazio/0000-0002-0019-7929; Anney,
Richard/0000-0002-6083-407X; Agartz, Ingrid/0000-0002-9839-5391; Nothen,
Markus/0000-0002-8770-2464; Ribases, Marta/0000-0003-1039-1116; Donohoe,
Gary/0000-0003-3037-7426; Sanders, Stephan/0000-0001-9112-5148; Buccola,
Nancy/0000-0003-1378-4636; Ramos-Quiroga, Josep
Antoni/0000-0003-1622-0350; Escott-Price, Valentina/0000-0003-1784-5483;
lichtenstein, paul/0000-0003-3037-5287; Kent,
Lindsey/0000-0002-5315-3399; Moran, Jennifer/0000-0002-5664-4716;
Nievergelt, Caroline/0000-0001-5766-8923; Goddard,
Michael/0000-0001-9917-7946; Schachar, Russell/0000-0002-2015-4395;
Zammit, Stanley/0000-0002-2647-9211; Herms, Stefan/0000-0002-2786-8200;
Stroup, Thomas/0000-0002-3123-0672; Morris, Derek/0000-0002-3413-570X;
Myin-Germeys, Inez/0000-0002-3731-4930; Jamain,
Stephane/0000-0002-4321-4100; Greenwood, Tiffany/0000-0002-6080-6503;
KELLER, MATTHEW/0000-0002-6075-9882; Nurnberger,
John/0000-0002-7674-1767; Gill, Michael/0000-0003-0206-5337; McMahon,
Francis/0000-0002-9469-305X; Corvin, Aiden/0000-0001-6717-4089;
MacIntyre, Donald J/0000-0001-6963-1335; O'Donovan,
Michael/0000-0001-7073-2379; Hamilton, Steven/0000-0001-8106-6260;
Barnes, Michael/0000-0001-9097-7381; Backlund, Lena/0000-0001-9399-5024;
Gallagher, Louise/0000-0001-9462-2836; Lesch,
Klaus-Peter/0000-0001-8348-153X; Willsey, Arthur/0000-0002-9922-3612;
Vicente, Astrid/0000-0001-7134-8037; Craig, Ian/0000-0002-4063-1005;
Bergen, Sarah/0000-0002-5888-0034; Anttila, Verneri/0000-0002-0073-4675;
Laukens, Debby/0000-0002-1984-5850; Wijsman, Ellen/0000-0002-2725-6669;
Matthews, Keith/0000-0002-4478-5888; Miranda, Ana/0000-0001-6998-5686;
Cormand, Bru/0000-0001-5318-4382; Montgomery, Grant/0000-0002-4140-8139;
Zhang, Peng/0000-0003-1182-1392; Mattheisen, Manuel/0000-0002-8442-493X;
Paterson, Andrew/0000-0002-9169-118X; Melle, Ingrid
/0000-0002-9783-548X; Schumacher, Johannes/0000-0001-9217-6457;
Ruderfer, Douglas/0000-0002-2365-386X; Lencz, Todd/0000-0001-8586-338X;
McQuillin, Andrew/0000-0003-1567-2240; Franke,
Andre/0000-0003-1530-5811; Monaco, Anthony/0000-0001-7480-3197; Bailey,
Anthony/0000-0003-4257-972X; Lee, Sang Hong/0000-0001-9701-2718; Breen,
Gerome/0000-0003-2053-1792; Hansen, Thomas/0000-0001-6703-7762; Wray,
Naomi/0000-0001-7421-3357; Holmans, Peter/0000-0003-0870-9412;
Sutcliffe, James/0000-0001-5200-6007
FU Australian Research Council [FT0991360, DE130100614]; Australian
National Health and Medical Research Council [613608, 1011506, 1047956];
National Institute of Mental Health (NIMH) [U01 MH085520]; Netherlands
Scientific Organization (NOW) [480-05-003]; Dutch Brain Foundation; VU
University
FX This research was directly supported by the Australian Research Council
(FT0991360 and DE130100614) and the Australian National Health and
Medical Research Council (613608, 1011506 and 1047956). The PGC
Cross-Disorder Group is supported by National Institute of Mental Health
(NIMH) grant U01 MH085520. Statistical analyses were carried out on the
Genetic Cluster Computer (see URLs), which is financially supported by
the Netherlands Scientific Organization (NOW; 480-05-003; principal
investigator D.P.) along with a supplement from the Dutch Brain
Foundation and VU University. Numerous (> 100) grants from government
agencies along with substantial private and foundation support worldwide
enabled the collection of phenotype and genotype data, without which
this research would not be possible; grant numbers are listed in primary
PGC publications or in the Supplementary Note.
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PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD SEP
PY 2013
VL 45
IS 9
BP 984
EP +
DI 10.1038/ng.2711
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA 209ID
UT WOS:000323748200007
ER
PT J
AU Smith, RP
Taher, L
Patwardhan, RP
Kim, MJ
Inoue, F
Shendure, J
Ovcharenko, I
Ahituv, N
AF Smith, Robin P.
Taher, Leila
Patwardhan, Rupali P.
Kim, Mee J.
Inoue, Fumitaka
Shendure, Jay
Ovcharenko, Ivan
Ahituv, Nadav
TI Massively parallel decoding of mammalian regulatory sequences supports a
flexible organizational model
SO NATURE GENETICS
LA English
DT Article
ID TRANSCRIPTION FACTORS; GENE-EXPRESSION; HEART ENHANCERS; IN-VIVO; DNA;
LIVER; ELEMENTS; BINDING; GENOME; DISSECTION
AB Despite continual progress in the cataloging of vertebrate regulatory elements, little is known about their organization and regulatory architecture. Here we describe a massively parallel experiment to systematically test the impact of copy number, spacing, combination and order of transcription factor binding sites on gene expression. A complex library of similar to 5,000 synthetic regulatory elements containing patterns from 12 liver-specific transcription factor binding sites was assayed in mice and in HepG2 cells. We find that certain transcription factors act as direct drivers of gene expression in homotypic clusters of binding sites, independent of spacing between sites, whereas others function only synergistically. Heterotypic enhancers are stronger than their homotypic analogs and favor specific transcription factor binding site combinations, mimicking putative native enhancers. Exhaustive testing of binding site permutations suggests that there is flexibility in binding site order. Our findings provide quantitative support for a flexible model of regulatory element activity and suggest a framework for the design of synthetic tissue-specific enhancers.
C1 [Smith, Robin P.; Kim, Mee J.; Inoue, Fumitaka; Ahituv, Nadav] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA.
[Smith, Robin P.; Kim, Mee J.; Inoue, Fumitaka; Ahituv, Nadav] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
[Taher, Leila; Ovcharenko, Ivan] NIH, Natl Ctr Biotechnol Informat, Computat Biol Branch, Natl Lib Med, Bethesda, MD USA.
[Taher, Leila] Univ Rostock, Inst Biostat & Informat Med & Ageing Res, D-18055 Rostock, Germany.
[Patwardhan, Rupali P.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
RP Shendure, J (reprint author), Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
EM shendure@u.washington.edu; ovcharen@nih.gov; nadav.ahituv@ucsf.edu
OI Ahituv, Nadav/0000-0002-7434-8144; Shendure, Jay/0000-0002-1516-1865
FU National Human Genome Research Institute (NHGRI) [1R01HG006768];
University of California, San Francisco (UCSF) Liver Center [P30
DK026743]; National Institute of Child and Human Development
[R01HD059862]; NHGRI [R01HG005058]; National Institute of General
Medical Sciences [GM61390]; National Institute of Neurological Disorders
and Stroke [1R01NS079231]; National Institute of Diabetes and Digestive
and Kidney Diseases [1R01DK090382]; Simons Foundation [SFARI 256769];
Canadian Institutes of Health Research (CIHR); US National Institutes of
Health [T32 GM007175]; UCSF Quantitative Biosciences Consortium
fellowship for Interdisciplinary Research; Amgen Research Excellence in
Bioengineering and Therapeutic Sciences fellowship; US National
Institutes of Health, National Library of Medicine
FX This work was supported by National Human Genome Research Institute
(NHGRI) grant 1R01HG006768 (N.A. and J.S.) and the Pilot/Feasibility
grant from the University of California, San Francisco (UCSF) Liver
Center (P30 DK026743). N.A. is also supported by National Institute of
Child and Human Development grant R01HD059862, NHGRI grant R01HG005058,
National Institute of General Medical Sciences grant GM61390, National
Institute of Neurological Disorders and Stroke grant 1R01NS079231,
National Institute of Diabetes and Digestive and Kidney Diseases grant
1R01DK090382 and the Simons Foundation (SFARI 256769). R. P. S. was
supported in part by a Canadian Institutes of Health Research (CIHR)
fellowship in hepatology. M.J.K. was supported in part by US National
Institutes of Health training grant T32 GM007175, the UCSF Quantitative
Biosciences Consortium fellowship for Interdisciplinary Research and the
Amgen Research Excellence in Bioengineering and Therapeutic Sciences
fellowship. This work was funded in part by the Intramural Research
Program of the US National Institutes of Health, National Library of
Medicine (I.O.).
NR 47
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PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD SEP
PY 2013
VL 45
IS 9
BP 1021
EP +
DI 10.1038/ng.2713
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 209ID
UT WOS:000323748200011
PM 23892608
ER
PT J
AU Xu, DY
Shen, WP
Guo, R
Xue, YT
Peng, W
Sima, J
Yang, J
Sharov, A
Srikantan, S
Yang, JD
Fox, D
Qian, Y
Martindale, JL
Piao, YL
Machamer, J
Joshi, SR
Mohanty, S
Shaw, AC
Lloyd, TE
Brown, GW
Ko, MSH
Gorospe, M
Zou, SG
Wang, WD
AF Xu, Dongyi
Shen, Weiping
Guo, Rong
Xue, Yutong
Peng, Wei
Sima, Jian
Yang, Jay
Sharov, Alexei
Srikantan, Subramanya
Yang, Jiandong
Fox, David, III
Qian, Yong
Martindale, Jennifer L.
Piao, Yulan
Machamer, James
Joshi, Samit R.
Mohanty, Subhasis
Shaw, Albert C.
Lloyd, Thomas E.
Brown, Grant W.
Ko, Minoru S. H.
Gorospe, Myriam
Zou, Sige
Wang, Weidong
TI Top3 beta is an RNA topoisomerase that works with fragile X syndrome
protein to promote synapse formation
SO NATURE NEUROSCIENCE
LA English
DT Article
ID MENTAL-RETARDATION PROTEIN; FOCAL ADHESION KINASE; MESSENGER-RNA;
III-ALPHA; DNA-DAMAGE; STRESS GRANULES; DROSOPHILA; FMRP; SCHIZOPHRENIA;
TRANSLATION
AB Topoisomerases are crucial for solving DNA topological problems, but they have not been linked to RNA metabolism. Here we show that human topoisomerase 3 beta (Top3 beta) is an RNA topoisomerase that biochemically and genetically interacts with FMRP, a protein that is deficient in fragile X syndrome and is known to regulate the translation of mRNAs that are important for neuronal function, abnormalities of which are linked to autism. Notably, the FMRP-Top3 beta interaction is abolished by a disease-associated mutation of FMRP, suggesting that Top3 beta may contribute to the pathogenesis of mental disorders. Top3 beta binds multiple mRNAs encoded by genes with neuronal functions linked to schizophrenia and autism. Expression of one such gene, that encoding protein tyrosine kinase 2 (ptk2, also known as focal adhesion kinase or FAK), is reduced in the neuromuscular junctions of Top3 beta mutant flies. Synapse formation is defective in Top3 beta mutant flies and mice, as well as in FMRP mutant flies and mice. Our findings suggest that Top3 beta acts as an RNA topoisomerase and works with FMRP to promote the expression of mRNAs that are crucial for neurodevelopment and mental health.
C1 [Xu, Dongyi; Shen, Weiping; Guo, Rong; Xue, Yutong; Peng, Wei; Yang, Jiandong; Fox, David, III; Wang, Weidong] NIA, Genome Instabil & Chromatin Remodeling Sect, NIH, Baltimore, MD 21224 USA.
[Xu, Dongyi] Peking Univ, Sch Life Sci, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China.
[Sima, Jian] NIA, Human Genet Sect, NIH, Baltimore, MD 21224 USA.
[Yang, Jay; Brown, Grant W.] Univ Toronto, Dept Biochem, Toronto, ON, Canada.
[Sharov, Alexei; Qian, Yong; Piao, Yulan; Ko, Minoru S. H.] NIA, Dev Genom & Aging Sect, NIH, Baltimore, MD 21224 USA.
[Srikantan, Subramanya; Martindale, Jennifer L.; Gorospe, Myriam] NIA, RNA Regulat Sect, Genet Lab, NIH, Baltimore, MD 21224 USA.
[Machamer, James; Lloyd, Thomas E.] Johns Hopkins Univ, Sch Med, Dept Neurol & Neurosci, Baltimore, MD USA.
[Joshi, Samit R.; Mohanty, Subhasis; Shaw, Albert C.] Yale Univ, Sch Med, Dept Internal Med, Infect Dis Sect, New Haven, CT 06510 USA.
[Zou, Sige] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA.
RP Zou, SG (reprint author), NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA.
EM zous@mail.nih.gov; wangw@grc.nia.nih.gov
OI srikantan, subramanya/0000-0003-1810-6519; Xu,
Dongyi/0000-0001-5711-2618
FU Intramural Research Program of the NIA [Z01 AG000657-08]; NIH; Johns
Hopkins Center for Neuroscience Research [NS050274]; Canadian Institutes
of Health research grant [MOP-79368]; National Basic Research Program of
China [2013CB911002]; National Natural Science Foundation of China
[31271435]
FX We thank T. Hsieh (Duke University) for Drosophila Top3 beta reagents;
J.C. Wang (Harvard University) for Top3 beta knockout mice; D. Zarnescu
(University of Illinois), T. Jongens (University of Pennsylvania) and G.
Dreyfuss (University of Pennsylvania) for dfmr1 fly strains and
antibodies; S. Warren (Emory University), S. Ceman (University of
Illinois) and Y. Feng (Emory University) for vectors of FMR1 variants;
U. Fischer (University of Wuerzburg) for vectors of TDRD3 and FMR1
orthologs; A. Hoogeveen (Erasmus University) for FXR1 and FXR2
antibodies; R. Hynes (Massachusetts Institute of Technology) and R.
Palmer (Umea University) for FAK reagents; T. Enomoto (Tohoku
University) for Top3b-/-DT40 cells; and R. Hanai (Rikkyo
University) for the Top3 beta vector. We thank E. Chen, D.J. Pan and Y.
Feng for advice and assistance, S. K. Lee for assistance and D.
Schlessinger for support and critical reading of the manuscript. This
work is supported in part by the Intramural Research Program of the NIA
(Z01 AG000657-08), the NIH, the Johns Hopkins Center for Neuroscience
Research (NS050274), Canadian Institutes of Health research grant
MOP-79368 (to G. W. B.), the National Basic Research Program of China
(2013CB911002) and the National Natural Science Foundation of China
(31271435). This study used the high-performance computational
capabilities of the Biowulf Linux cluster at the NIH, Bethesda,
Maryland, USA (http://biowulf.nih.gov).
NR 63
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PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD SEP
PY 2013
VL 16
IS 9
BP 1238
EP U112
DI 10.1038/nn.3479
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA 207KN
UT WOS:000323597500015
PM 23912945
ER
PT J
AU Mathur, BN
Tanahira, C
Tamamaki, N
Lovinger, DM
AF Mathur, Brian N.
Tanahira, Chiyoko
Tamamaki, Nobuaki
Lovinger, David M.
TI Voltage drives diverse endocannabinoid signals to mediate striatal
microcircuit-specific plasticity
SO NATURE NEUROSCIENCE
LA English
DT Article
ID ACID AMIDE HYDROLASE; MEDIUM SPINY NEURONS; PARVALBUMIN-IMMUNOREACTIVE
NEURONS; DIACYLGLYCEROL LIPASE-ALPHA; FAST-SPIKING INTERNEURONS;
LONG-TERM DEPRESSION; PROJECTION NEURONS; BASAL GANGLIA; MICE LACKING;
SYNAPTIC-TRANSMISSION
AB The dorsolateral striatum and cannabinoid type 1 receptor (CB1) signaling mediate habitual action learning, which is thought to require a balance of activity in the direct and indirect striatal output pathways. However, very little is known about how the high CB1-expressing striatal inhibitory microcircuitry might contribute to long-term plasticity capable of sculpting direct and indirect pathway output. Using optogenetic and molecular interrogation of striatal GABAergic microcircuits, we examined voltage-dependent long-term depression of inhibitory synapses (iLTD) onto mouse and rat medium spiny projection neurons (MSNs). The observed iLTD involved recruitment of different endocannabinoid types and showed both presynaptic and postsynaptic selectivity for MSN subtypes, ultimately resulting in a powerful disinhibition of direct pathway MSNs. These results suggest a new role for voltage states in gating circuit-specific forms of synaptic plasticity and illuminate possible circuit dynamics underlying action control.
C1 [Mathur, Brian N.; Lovinger, David M.] NIAAA, Sect Synapt Pharmacol, Lab Integrat Neurosci, US Natl Inst Hlth, Bethesda, MD USA.
[Tanahira, Chiyoko; Tamamaki, Nobuaki] Kumamoto Univ, Grad Sch Med, Dept Morphol Neural Sci, Honjo, Kumamoto, Japan.
RP Lovinger, DM (reprint author), NIAAA, Sect Synapt Pharmacol, Lab Integrat Neurosci, US Natl Inst Hlth, Bethesda, MD USA.
EM lovindav@mail.nih.gov
FU Intramural NIH HHS [Z99 AA999999]
NR 50
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U2 17
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD SEP
PY 2013
VL 16
IS 9
BP 1275
EP U157
DI 10.1038/nn.3478
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 207KN
UT WOS:000323597500019
PM 23892554
ER
PT J
AU Cole, MW
Reynolds, JR
Power, JD
Repovs, G
Anticevic, A
Braver, TS
AF Cole, Michael W.
Reynolds, Jeremy R.
Power, Jonathan D.
Repovs, Grega
Anticevic, Alan
Braver, Todd S.
TI Multi-task connectivity reveals flexible hubs for adaptive task control
SO NATURE NEUROSCIENCE
LA English
DT Article
ID HUMAN CEREBRAL-CORTEX; INTRINSIC FUNCTIONAL CONNECTIVITY; PREFRONTAL
CORTEX; COGNITIVE CONTROL; HUMAN BRAIN; PSYCHOPHYSIOLOGICAL
INTERACTIONS; FRONTOPARIETAL CORTEX; VISUAL-ATTENTION; NETWORKS; REGIONS
AB Extensive evidence suggests that the human ability to adaptively implement a wide variety of tasks is preferentially a result of the operation of a fronto-parietal brain network (FPN). We hypothesized that this network's adaptability is made possible by flexible hubs: brain regions that rapidly update their pattern of global functional connectivity according to task demands. Using recent advances in characterizing brain network organization and dynamics, we identified mechanisms consistent with the flexible hub theory. We found that the FPN's brain-wide functional connectivity pattern shifted more than those of other networks across a variety of task states and that these connectivity patterns could be used to identify the current task. Furthermore, these patterns were consistent across practiced and novel tasks, suggesting that reuse of flexible hub connectivity patterns facilitates adaptive (novel) task performance. Together, these findings support a central role for fronto-parietal flexible hubs in cognitive control and adaptive implementation of task demands.
C1 [Cole, Michael W.; Braver, Todd S.] Washington Univ, Dept Psychol, St Louis, MO 63130 USA.
[Reynolds, Jeremy R.] Univ Denver, Dept Psychol, Denver, CO 80208 USA.
[Power, Jonathan D.] Washington Univ, Dept Psychol, St Louis, MO USA.
[Repovs, Grega] Univ Ljubljana, Dept Psychol, Ljubljana 61000, Slovenia.
[Anticevic, Alan] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA.
[Anticevic, Alan] Yale Univ, Abraham Ribicoff Res Facil, New Haven, CT USA.
[Anticevic, Alan] Natl Inst Alcohol Abuse, New Haven, CT USA.
[Anticevic, Alan] Alcoholism Ctr Translat Neurosci Alcoholism, New Haven, CT USA.
RP Cole, MW (reprint author), Washington Univ, Dept Psychol, St Louis, MO 63130 USA.
EM mwcole@mwcole.net
RI Cole, Michael/G-1056-2010;
OI Cole, Michael/0000-0003-4329-438X; Repovs, Grega/0000-0003-1837-3879;
Braver, Todd/0000-0002-2631-3393
FU US National Institutes of Health [K99MH096801, DP5OD012109-01]; Brain
and Behavior Research Foundation (NARSAD) Young Investigator Award
FX We thank S. Petersen, D. Bassett and J. Etzel for helpful feedback and
suggestions during preparation of this manuscript. We also thank W.
Schneider for access to data from his laboratory. Our work was supported
by the US National Institutes of Health under awards K99MH096801
(M.W.C.), DP5OD012109-01 (A.A.) and a Brain and Behavior Research
Foundation (NARSAD) Young Investigator Award (A.A.).
NR 58
TC 222
Z9 223
U1 11
U2 87
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD SEP
PY 2013
VL 16
IS 9
BP 1348
EP U247
DI 10.1038/nn.3470
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 207KN
UT WOS:000323597500028
PM 23892552
ER
PT J
AU Milner, JD
Holland, SM
AF Milner, Joshua D.
Holland, Steven M.
TI The cup runneth over: lessons from the ever-expanding pool of primary
immunodeficiency diseases
SO NATURE REVIEWS IMMUNOLOGY
LA English
DT Review
ID HYPER-IGE SYNDROME; CHRONIC MUCOCUTANEOUS CANDIDIASIS; HERPES-SIMPLEX
ENCEPHALITIS; ACUTE MYELOID-LEUKEMIA; T-CELL SURVIVAL;
IMMUNOGLOBULIN-SECRETING CELLS; HYPOMORPHIC RAG1 MUTATIONS; FUNCTION
STAT1 MUTATIONS; OF-FUNCTION MUTATIONS; B-CELL
AB A recent surge in newly described primary immunodeficiencies (PIDs) has highlighted new physiological and pathophysiological pathways that affect the immune system. Furthermore, the study of individuals with PIDs has substantially improved our understanding of basic cellular and signalling pathways in host defence and immune regulation. Single-gene defects can lead to disease manifestations that range from extremely narrow infectious phenotypes to remarkably broad multisystem effects. Hypomorphic or hypermorphic gene mutations often occur in human diseases; when coupled with the fact that humans are exposed to naturally encountered antigens and pathogens, this helps to make the case that the study of immunological diseases in humans should be at the forefront of basic immunological research.
C1 [Milner, Joshua D.] NIAID, Allerg Inflammat Unit, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Holland, Steven M.] NIAID, Lab Clin Infect Dis, Clin Res Ctr B34141, NIH, Bethesda, MD 20892 USA.
RP Milner, JD (reprint author), NIAID, Allerg Inflammat Unit, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jdmilner@niaid.nih.go; smh@nih.gov
FU Division of Intramural Research, US National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This work has been supported by the Division of Intramural Research, US
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 122
TC 38
Z9 38
U1 1
U2 23
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1733
J9 NAT REV IMMUNOL
JI Nat. Rev. Immunol.
PD SEP
PY 2013
VL 13
IS 9
BP 635
EP 648
DI 10.1038/nri3493
PG 14
WC Immunology
SC Immunology
GA 208BA
UT WOS:000323648900009
PM 23887241
ER
PT J
AU Kwong, PD
Mascola, JR
Nabel, GJ
AF Kwong, Peter D.
Mascola, John R.
Nabel, Gary J.
TI Broadly neutralizing antibodies and the search for an HIV-1 vaccine: the
end of the beginning
SO NATURE REVIEWS IMMUNOLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODIES; CROSS-CLADE
NEUTRALIZATION; MUCOSAL SHIV CHALLENGE; B-CELL RESPONSES; STRUCTURAL
BASIS; POTENT NEUTRALIZATION; ENVELOPE GLYCOPROTEIN; HIV-1-INFECTED
INDIVIDUALS; CRYSTAL-STRUCTURE
AB The field of HIV-1 vaccine research has seen a renaissance with the identification of antibodies that neutralize most circulating HIV-1 strains. An understanding of the structural mode of target recognition that these antibodies use and the immune pathways that lead to their development is emerging. This knowledge has provided fundamental insights into the pathways that elicit broadly neutralizing antibodies and provides a foundation for active and passive immunization strategies to prevent HIV-1 infection.
C1 [Kwong, Peter D.; Mascola, John R.; Nabel, Gary J.] NIAID, Vaccine Res Ctr, US Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Nabel, GJ (reprint author), Sanofi, 640 Mem Dr, Cambridge, MA 02139 USA.
EM Gary.Nabel@sanofi.com
RI Cheng, Yushao/E-6256-2011
FU Intramural Research Program of the Vaccine Research Center, National
Institute of Allergy and Infectious Diseases, US National Institutes of
Health
FX We thank B. Hartman and J. Stuckey for assistance with display items, J.
Gorman for modelling for Figure 1, A. Tislerics for manuscript
preparation, N. Michael for helpful discussions, and members of the
Virology Laboratory, the Structural Biology Section, the Structural
Bioinformatics Core, and the Humoral Immunology Section, Vaccine
Research Center, for discussions and comments on the manuscript. Support
for this work was provided by the Intramural Research Program of the
Vaccine Research Center, National Institute of Allergy and Infectious
Diseases, US National Institutes of Health.
NR 104
TC 128
Z9 130
U1 5
U2 73
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1733
J9 NAT REV IMMUNOL
JI Nat. Rev. Immunol.
PD SEP
PY 2013
VL 13
IS 9
BP 693
EP 701
DI 10.1038/nri3516
PG 9
WC Immunology
SC Immunology
GA 208BA
UT WOS:000323648900013
PM 23969737
ER
PT J
AU Zhong, L
Wang, JTL
Wen, DR
Aris, V
Soteropoulos, P
Shapiro, BA
AF Zhong, Ling
Wang, Jason T. L.
Wen, Dongrong
Aris, Virginie
Soteropoulos, Patricia
Shapiro, Bruce A.
TI Effective Classification of MicroRNA Precursors Using Feature Mining and
AdaBoost Algorithms
SO OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY
LA English
DT Article
ID SUPPORT VECTOR MACHINES; SEQUENCING DATA; CIRCULATING MICRORNAS;
EXPRESSION; IDENTIFICATION; PREDICTION; CELLS; GENES; RNAS; DROSOPHILA
AB MicroRNAs play important roles in most biological processes, including cell proliferation, tissue differentiation, and embryonic development, among others. They originate from precursor transcripts (pre-miRNAs), which contain phylogenetically conserved stem-loop structures. An important bioinformatics problem is to distinguish the pre-miRNAs from pseudo pre-miRNAs that have similar stem-loop structures. We present here a novel method for tackling this bioinformatics problem. Our method, named MirID, accepts an RNA sequence as input, and classifies the RNA sequence either as positive (i.e., a real pre-miRNA) or as negative (i.e., a pseudo pre-miRNA). MirID employs a feature mining algorithm for finding combinations of features suitable for building pre-miRNA classification models. These models are implemented using support vector machines, which are combined to construct a classifier ensemble. The accuracy of the classifier ensemble is further enhanced by the utilization of an AdaBoost algorithm. When compared with two closely related tools on twelve species analyzed with these tools, MirID outperforms the existing tools on the majority of the twelve species. MirID was also tested on nine additional species, and the results showed high accuracies on the nine species. The MirID web server is fully operational and freely accessible at http://bioinformatics.njit.edu/MirID/. Potential applications of this software in genomics and medicine are also discussed.
C1 [Zhong, Ling; Wang, Jason T. L.; Wen, Dongrong] New Jersey Inst Technol, Bioinformat Program, Newark, NJ 07102 USA.
[Zhong, Ling; Wang, Jason T. L.; Wen, Dongrong] New Jersey Inst Technol, Dept Comp Sci, Newark, NJ 07102 USA.
[Aris, Virginie; Soteropoulos, Patricia] Univ Med & Dent New Jersey, New Jersey Med Sch, Publ Hlth Res Inst, Ctr Appl Genom, Newark, NJ 07103 USA.
[Shapiro, Bruce A.] NCI, Computat RNA Struct Grp, Ctr Canc Res, Nanobiol Program, Frederick, MD 21701 USA.
RP Wang, JTL (reprint author), New Jersey Inst Technol, Bioinformat Program, GITC Bldg,Room 4211,218 Cent Ave, Newark, NJ 07102 USA.
EM wangj@njit.edu
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research
FX We thank the reviewers for their thoughtful comments and constructive
suggestions. This research was supported in part by the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research. The current findings were presented in part in
preliminary form in the Proceedings of the 2012 IEEE International
Conference on Bioinformatics and Biomedicine (Zhong et al., 2012).
NR 57
TC 4
Z9 4
U1 0
U2 16
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1536-2310
J9 OMICS
JI OMICS
PD SEP 1
PY 2013
VL 17
IS 9
BP 486
EP 493
DI 10.1089/omi.2013.0011
PG 8
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 210HD
UT WOS:000323820700004
PM 23808606
ER
PT J
AU McGowen, MR
Weckle, A
Agnew, D
Benirschke, K
Savage-Rumbaugh, S
Kim, CJ
Wagner, GP
Romero, R
Wildman, DE
AF McGowen, Michael R.
Weckle, Amy
Agnew, Dalen
Benirschke, Kurt
Savage-Rumbaugh, Sue
Kim, Chong Jai
Wagner, Guenter P.
Romero, Robert
Wildman, Derek E.
TI GENE EXPRESSION IN THE TERM PLACENTA OF THE OPOSSUM MONODELPHIS
DOMESTICA AND THE EVOLUTION OF THE THERIAN PLACENTA
SO PLACENTA
LA English
DT Meeting Abstract
CT Meeting of the International-Federation-of-Placenta-Associations (IFPA)
CY SEP 11-14, 2013
CL Whistler, CANADA
SP Int Federat Placenta Assoc (IFPA)
C1 [McGowen, Michael R.; Weckle, Amy; Wildman, Derek E.] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI USA.
[Agnew, Dalen] Michigan State Univ, Coll Vet Med, Diagnost Ctr Populat & Anim Hlth, E Lansing, MI 48824 USA.
[Benirschke, Kurt] Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA.
[Savage-Rumbaugh, Sue] Great Ape Trust Bonobo Hope Sanctuary, Des Moines, IA USA.
[Kim, Chong Jai] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA.
[Wagner, Guenter P.] Yale Univ, Dept Ecol & Evolutionary Biol, New Haven, CT USA.
[Wagner, Guenter P.] Yale Univ, Yale Syst Biol Inst, New Haven, CT USA.
[Kim, Chong Jai; Romero, Robert] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Detroit, MI USA.
[Wildman, Derek E.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
NR 0
TC 0
Z9 0
U1 2
U2 5
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0143-4004
J9 PLACENTA
JI Placenta
PD SEP
PY 2013
VL 34
IS 9
BP A24
EP A25
DI 10.1016/j.placenta.2013.06.075
PG 2
WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
GA 207GW
UT WOS:000323587900084
ER
PT J
AU Salafia, C
Yampolsky, M
Vulk, D
Stodgell, CJ
Katzman, PJ
Culhane, J
Landrigan, P
Szabo, S
Thieux, N
Swanson, J
Dole, N
Varner, MW
Moye, J
Miller, R
AF Salafia, Carolyn
Yampolsky, Michael
Vulk, Denis
Stodgell, C. J.
Katzman, P. J.
Culhane, J.
Landrigan, P.
Szabo, S.
Thieux, N.
Swanson, J.
Dole, N.
Varner, M. W.
Moye, John
Miller, Richard
TI MAPPING PLACENTAL TOPOLOGY FROM 3D SCANS, THE GRAPHIC DISPLAY OF
VARIATION IN ARBORISATION ACROSS GESTATION
SO PLACENTA
LA English
DT Meeting Abstract
CT Meeting of the International-Federation-of-Placenta-Associations (IFPA)
CY SEP 11-14, 2013
CL Whistler, CANADA
SP Int Federat Placenta Assoc (IFPA)
C1 [Salafia, Carolyn] Placental Analyt LLC, Larchmont, NY USA.
[Salafia, Carolyn] New York State Inst Basic Res Dev Disabil, Staten Isl, NY 10314 USA.
[Yampolsky, Michael] Univ Toronto, Toronto, ON, Canada.
[Vulk, Denis] Royal Inst Technol, Kungliga Tekniska Hogskolan, Stockholm, Sweden.
[Stodgell, C. J.; Katzman, P. J.; Culhane, J.; Landrigan, P.; Szabo, S.; Thieux, N.; Swanson, J.; Dole, N.; Varner, M. W.; Moye, John; Miller, Richard] Natl Childrens Study Placenta Consortium, Bethesda, MD USA.
[Stodgell, C. J.; Katzman, P. J.; Miller, Richard] Univ Rochester, Sch Med & Dent, Rochester, NY USA.
[Culhane, J.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Landrigan, P.] Mt Sinai Sch Med, New York, NY USA.
[Szabo, S.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Thieux, N.] S Dakota State Univ, Brookings, SD USA.
[Swanson, J.] Univ Calif Irvine, Irvine, CA USA.
[Dole, N.] Univ N Carolina, Chapel Hill, NC USA.
[Varner, M. W.] Univ Utah, Salt Lake City, UT USA.
[Moye, John] NIH, Natl Childrens Study, Bethesda, MD 20892 USA.
OI Stodgell, Christopher/0000-0002-1666-5299
NR 0
TC 1
Z9 1
U1 0
U2 2
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0143-4004
J9 PLACENTA
JI Placenta
PD SEP
PY 2013
VL 34
IS 9
BP A73
EP A74
DI 10.1016/j.placenta.2013.06.219
PG 2
WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
GA 207GW
UT WOS:000323587900227
ER
PT J
AU Salafia, C
Girardi, T
Yampolsky, M
Shlakhter, O
Newschaffer, C
Fallin, D
Walker, C
Stodgell, CJ
Katzman, PJ
Culhane, J
Landrigan, P
Szabo, S
Thieux, N
Swanson, J
Dole, N
Varner, MW
Moye, J
Miller, R
AF Salafia, Carolyn
Girardi, Theresa
Yampolsky, Michael
Shlakhter, Oleksandr
Newschaffer, Craig
Fallin, Danielle
Walker, Cheryl
Stodgell, C. J.
Katzman, P. J.
Culhane, J.
Landrigan, P.
Szabo, S.
Thieux, N.
Swanson, J.
Dole, N.
Varner, M. W.
Moye, John
Miller, Richard
TI CHORIONIC VASCULAR STRUCTURE AND PLACENTAL FUNCTIONAL EFFICIENCY (BETA)
DIFFER IN HIGH AND LOW AUTISM RISK PLACENTAL COHORTS
SO PLACENTA
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Federation-of-Placenta-Associations
(IFPA)
CY SEP 11-14, 2013
CL Whistler, CANADA
SP Int Federat Placenta Assoc (IFPA)
C1 [Salafia, Carolyn; Girardi, Theresa; Yampolsky, Michael] Placental Analyt LLC, Larchmont, NY USA.
[Salafia, Carolyn; Girardi, Theresa] New York State Off Mental Retardat & Dev Disabil, Inst Basic Res, Staten Isl, NY USA.
[Yampolsky, Michael; Shlakhter, Oleksandr] Univ Toronto, Toronto, ON, Canada.
[Shlakhter, Oleksandr] Alberta Hlth Serv, Edmonton, AB, Canada.
[Newschaffer, Craig] Drexel Univ, Philadelphia, PA 19104 USA.
[Fallin, Danielle] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Walker, Cheryl] Univ Calif Davis, Davis, CA 95616 USA.
[Stodgell, C. J.; Katzman, P. J.; Culhane, J.; Landrigan, P.; Szabo, S.; Thieux, N.; Swanson, J.; Dole, N.; Varner, M. W.; Moye, John; Miller, Richard] Natl Childrens Study Placenta Consortium, Bethesda, MD USA.
[Stodgell, C. J.; Katzman, P. J.; Miller, Richard] Univ Rochester, Sch Med & Dent, Rochester, NY USA.
[Culhane, J.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Landrigan, P.] Mt Sinai Sch Med, New York, NY USA.
[Szabo, S.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Thieux, N.] S Dakota State Univ, Brookings, SD 57007 USA.
[Swanson, J.] Univ Calif Irvine, Irvine, CA USA.
[Dole, N.] Univ N Carolina, Chapel Hill, NC USA.
[Varner, M. W.] Univ Utah, Salt Lake City, UT USA.
[Moye, John] NIH, Natl Childrens Study, Bethesda, MD 20892 USA.
OI Stodgell, Christopher/0000-0002-1666-5299
NR 0
TC 0
Z9 0
U1 0
U2 1
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0143-4004
J9 PLACENTA
JI Placenta
PD SEP
PY 2013
VL 34
IS 9
BP A72
EP A72
DI 10.1016/j.placenta.2013.06.217
PG 1
WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
GA 207GW
UT WOS:000323587900225
ER
PT J
AU Salafia, C
Misra, D
Stodgell, C
Katzman, P
Ruffolo, L
Culhane, J
Wadlinger, S
Wapner, R
Torres, C
Landrigan, P
Littman, L
Sheffield, P
Leuthner, S
Szabo, S
Thieux, N
Specker, B
Swanson, J
Miller, RK
Moye, J
Durkin, M
AF Salafia, Carolyn
Misra, Dawn
Stodgell, C.
Katzman, P.
Ruffolo, L.
Culhane, J.
Wadlinger, S.
Wapner, R.
Torres, C.
Landrigan, P.
Littman, L.
Sheffield, P.
Leuthner, S.
Szabo, S.
Thieux, N.
Specker, B.
Swanson, J.
Miller, R. K.
Moye, John
Durkin, M.
TI THE MAJORTIY OF VARIANCE IN BIRTHWEIGHT RELATIVE TO PLACENTAL WEIGHT (AS
BETA = LN(PW)/LN(BW) IS ACCOUNTED FOR BY DETAILED NOVEL PLACENTAL
MEASURES: IMPLICATIONS FOR FETAL ORIGINS WORK
SO PLACENTA
LA English
DT Meeting Abstract
CT Meeting of the International-Federation-of-Placenta-Associations (IFPA)
CY SEP 11-14, 2013
CL Whistler, CANADA
SP Int Federat Placenta Assoc (IFPA)
C1 [Salafia, Carolyn; Misra, Dawn] Placental Analyt LLC, Larchmont, NY USA.
[Salafia, Carolyn; Misra, Dawn; Stodgell, C.; Katzman, P.; Ruffolo, L.; Culhane, J.; Wadlinger, S.; Wapner, R.; Torres, C.; Landrigan, P.; Littman, L.; Sheffield, P.; Leuthner, S.; Szabo, S.; Thieux, N.; Specker, B.; Swanson, J.; Miller, R. K.; Moye, John; Durkin, M.] Natl Childrens Study Placenta Consortium, Bethesda, MD USA.
[Stodgell, C.; Katzman, P.; Ruffolo, L.; Miller, R. K.] Univ Rochester, Sch Med & Dent, Rochester, NY USA.
[Culhane, J.; Wadlinger, S.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Wapner, R.; Torres, C.] Columbia Univ, New York, NY USA.
[Landrigan, P.; Littman, L.; Sheffield, P.] Icahn Schhol Med, New York, NY USA.
[Leuthner, S.; Szabo, S.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Thieux, N.; Specker, B.] S Dakota State Univ, Brookings, SD 57007 USA.
[Swanson, J.] Univ Calif Irvine, Irvine, CA USA.
[Salafia, Carolyn; Misra, Dawn; Stodgell, C.; Katzman, P.; Ruffolo, L.; Culhane, J.; Wadlinger, S.; Wapner, R.; Torres, C.; Landrigan, P.; Littman, L.; Sheffield, P.; Leuthner, S.; Szabo, S.; Thieux, N.; Specker, B.; Swanson, J.; Miller, R. K.; Moye, John; Durkin, M.] Univ N Carolina, Chapel Hill, NC USA.
[Salafia, Carolyn; Misra, Dawn; Stodgell, C.; Katzman, P.; Ruffolo, L.; Culhane, J.; Wadlinger, S.; Wapner, R.; Torres, C.; Landrigan, P.; Littman, L.; Sheffield, P.; Leuthner, S.; Szabo, S.; Thieux, N.; Specker, B.; Swanson, J.; Miller, R. K.; Moye, John; Durkin, M.] Univ Utah, Salt Lake City, UT USA.
[Durkin, M.] Univ Wisconsin, Madison, WI USA.
[Moye, John] NIH, Natl Childrens Study, Bethesda, MD 20892 USA.
RI Durkin, Maureen/B-7834-2015
NR 0
TC 0
Z9 0
U1 0
U2 3
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0143-4004
J9 PLACENTA
JI Placenta
PD SEP
PY 2013
VL 34
IS 9
BP A14
EP A15
DI 10.1016/j.placenta.2013.06.044
PG 2
WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
GA 207GW
UT WOS:000323587900053
ER
PT J
AU Koscso, B
Trepakov, A
Csoka, B
Nemeth, ZH
Pacher, P
Eltzschig, HK
Hasko, G
AF Koscso, Balazs
Trepakov, Alexey
Csoka, Balazs
Nemeth, Zoltan H.
Pacher, Pal
Eltzschig, Holger K.
Hasko, Gyoergy
TI Stimulation of A(2B) adenosine receptors protects against
trauma-hemorrhagic shock-induced lung injury
SO PURINERGIC SIGNALLING
LA English
DT Article
DE Trauma; Hemorrhagic shock; A(2B) adenosine receptor; BAY 60-6583
ID MULTIPLE ORGAN FAILURE; CARDIAC DYSFUNCTION; MACROPHAGE FUNCTION;
TNF-ALPHA; INFLAMMATION; IL-10; MICE; RESUSCITATION; ACTIVATION;
MECHANISMS
AB Inflammation is responsible for secondary organ failure after trauma and hemorrhagic shock (T/HS). Adenosine, acting through four G protein-coupled cell surface receptors, A(1), A(2A), A(2B), and A(3), exerts a number of tissue protective and anti-inflammatory effects. The goal of the present study was to test the effect of A(2B) adenosine receptor stimulation on T/HS-induced organ injury and inflammation in rats. Rats after T/HS were resuscitated with Ringer's lactate containing the A(2B) receptor agonist BAY 60-6583 or its vehicle. We found that BAY 60-6583 decreased T/HS-induced lung permeability and plasma creatine kinase levels but failed to affect T/HS-induced lung neutrophil infiltration and I kappa B alpha expression and plasma alanine aminotransferase levels. Thus, we conclude that stimulation of A(2B) receptors protects against T/HS-induced lung and muscle injury.
C1 [Koscso, Balazs; Trepakov, Alexey; Csoka, Balazs; Hasko, Gyoergy] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA.
[Eltzschig, Holger K.] Univ Colorado, Sch Med, Dept Anesthesiol, Mucosal Inflammat Program, Aurora, CO USA.
[Nemeth, Zoltan H.] Morristown Med Ctr, Dept Surg, Morristown, NJ USA.
[Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, Bethesda, MD USA.
[Hasko, Gyoergy] Univ Debrecen, Med & Hlth Sci Ctr, Dept Med Chem, H-4012 Debrecen, Hungary.
RP Hasko, G (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, 185 S Orange Ave, Newark, NJ 07103 USA.
EM haskoge@umdnj.edu
RI Pacher, Pal/B-6378-2008;
OI Pacher, Pal/0000-0001-7036-8108; Csoka, Balazs/0000-0002-7562-1130
FU National Institutes of Health [R01GM066189]; USAMRMC [09065004,
W81XWH-10-1-1015]; Hungarian Scientific Research Fund (OTKA) [CK 78275];
National Heart Institute [R01-HL0921, R01-DK083385, R01-HL098294];
Crohn's and Colitis Foundation of America
FX This work was supported by National Institutes of Health grants
R01GM066189; USAMRMC grant log# 09065004 (contract W81XWH-10-1-1015);
Hungarian Scientific Research Fund (OTKA) grant CK 78275 to GH; National
Heart Institute Grants R01-HL0921, R01-DK083385, and R01-HL098294; and a
grant by the Crohn's and Colitis Foundation of America to HKE.
NR 30
TC 2
Z9 2
U1 0
U2 10
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1573-9538
EI 1573-9546
J9 PURINERG SIGNAL
JI Purinergic Signal.
PD SEP
PY 2013
VL 9
IS 3
BP 427
EP 432
DI 10.1007/s11302-013-9362-7
PG 6
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 209HQ
UT WOS:000323746700011
PM 23584760
ER
PT J
AU Choyke, PL
AF Choyke, Peter L.
TI Science to Practice: Imaging Cancer-associated Fibroblasts: No Innocent
Bystanders
SO RADIOLOGY
LA English
DT Editorial Material
ID TUMOR STROMA
AB The era of stromal-based therapies is coming, and methods to image the stroma are likely to become vital to improved understanding of the intricate interrelationships of these cells. Because fibroblasts are so important for the initiation of cancer, stromal-based therapies may serve as preventive regimens in patients who are at high risk for recurrent disease. The method described by Vandsburger et al uses a reporter-gene magnetic resonance (MR) imaging- agent paradigm that withstands dilution from cell division while allowing imaging without ionizing radiation. The requirement for gene transfection makes near-term clinical translation unlikely, but the opportunities for studying cancer-associated fibroblast activity in tumor models and observing and modulating their migratory behavior is an exciting prospect, one that is hoped to bring tangible benefits to patients with cancer.
C1 NCI, Mol Imaging Program, Bethesda, MD 20892 USA.
RP Choyke, PL (reprint author), NCI, Mol Imaging Program, Bldg 10,Room B3B69F, Bethesda, MD 20892 USA.
EM pchoyke@nih.gov
NR 7
TC 1
Z9 1
U1 0
U2 6
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD SEP
PY 2013
VL 268
IS 3
BP 617
EP 618
DI 10.1148/radiol.13131447
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 205CR
UT WOS:000323419300001
PM 23970505
ER
PT J
AU Pinsky, PF
Gierada, DS
Nath, PH
Kazerooni, E
Amorosa, J
AF Pinsky, Paul F.
Gierada, David S.
Nath, P. Hrudaya
Kazerooni, Ella
Amorosa, Judith
TI National Lung Screening Trial: Variability in Nodule Detection Rates in
Chest CT Studies
SO RADIOLOGY
LA English
DT Article
ID SEMIAUTOMATED VOLUME MEASUREMENTS; LOW-DOSE CT; CANCER; RADIOLOGISTS;
AGREEMENT; ACCURACY
AB Purpose: To characterize the variability in radiologists' interpretations of computed tomography (CT) studies in the National Lung Screening Trial (NLST) (including assessment of false-positive rates [FPRs] and sensitivity), to examine factors that contribute to variability, and to evaluate trade-offs between FPRs and sensitivity among different groups of radiologists.
Materials and Methods: The HIPAA-compliant NLST was approved by the institutional review board at each screening center; all participants provided informed consent. NLST radiologists reported overall screening results, nodule-specific findings, and recommendations for diagnostic follow-up. A noncalcified nodule of 4 mm or larger constituted a positive screening result. The FPR was defined as the rate of positive screening examinations in participants without a cancer diagnosis within 1 year. Descriptive analyses and mixed-effects models were utilized. The average odds ratio (OR) for a false-positive result across all pairs of radiologists was used as a measure of variability.
Results: One hundred twelve radiologists at 32 screening centers each interpreted 100 or more NLST CT studies, interpreting 72 160 of 75 126 total NLST CT studies in aggregate. The mean FPR for radiologists was 28.7% +/- 13.7 (standard deviation), with a range of 3.8%-69.0%. The model yielded an average OR of 2.49 across all pairs of radiologists and an OR of 1.83 for pairs within the same screening center. Mean FPRs were similar for academic versus nonacademic centers (27.9% and 26.7%, respectively) and for centers inside (25.0%) versus outside (28.7%) the U. S. "histoplasmosis belt." Aggregate sensitivity was 96.5% for radiologists with FPRs higher than the median (27.1%), compared with 91.9% for those with FPRs lower than the median (P = .02).
Conclusion: There was substantial variability in radiologists' FPRs. Higher FPRs were associated with modestly higher sensitivity. (C)RSNA, 2013
C1 [Pinsky, Paul F.] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Gierada, David S.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA.
[Nath, P. Hrudaya] Univ Alabama Birmingham, Dept Radiol, Birmingham, AL USA.
[Kazerooni, Ella] Univ Michigan, Dept Radiol, Sch Med, Ann Arbor, MI 48109 USA.
[Amorosa, Judith] New Jersey Med Coll, Canc Inst New Jersey, New Brunswick, NJ USA.
RP Pinsky, PF (reprint author), NCI, Canc Prevent Div, NIH, 6130 Execut Blvd, Bethesda, MD 20892 USA.
EM pp4f@nih.gov
FU National Institutes of Health [U01-CA-80098, U01-CA-79778, N01-CN-25514,
N01-CN-25522, N01-CN-25515, N01-CN-25512, N01-CN-25513, N01-CN-25516,
N01-CN-25511, N01-CN-25524, N01-CN-25518, N01-CN-75022]
FX This research was supported by the National Institutes of Health (grants
U01-CA-80098 and U01-CA-79778 and contracts N01-CN-25514, N01-CN-25522,
N01-CN-25515, N01-CN-25512, N01-CN-25513, N01-CN-25516, N01-CN-25511,
N01-CN-25524, N01-CN-25518, and N01-CN-75022).
NR 16
TC 16
Z9 16
U1 0
U2 10
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD SEP
PY 2013
VL 268
IS 3
BP 865
EP 873
DI 10.1148/radiol.13121530
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 205CR
UT WOS:000323419300028
PM 23592767
ER
PT J
AU Chen, MY
Shanbhag, SM
Arai, AE
AF Chen, Marcus Y.
Shanbhag, Sujata M.
Arai, Andrew E.
TI Radiation Dose of Second-Generation 320-Detector Row CT Response
SO RADIOLOGY
LA English
DT Letter
C1 [Chen, Marcus Y.; Shanbhag, Sujata M.; Arai, Andrew E.] NHLBI, Adv Cardiovasc Imaging Lab, Cardiovasc & Pulm Branch, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Chen, MY (reprint author), NHLBI, Adv Cardiovasc Imaging Lab, Cardiovasc & Pulm Branch, NIH,Dept Hlth & Human Serv, 10 Ctr Dr,Bldg 10,Room B1D416, Bethesda, MD 20892 USA.
EM marcus.chen@nih.gov
NR 3
TC 0
Z9 0
U1 0
U2 0
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD SEP
PY 2013
VL 268
IS 3
BP 928
EP 928
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 205CR
UT WOS:000323419300043
PM 24137710
ER
PT J
AU Cheng, J
Chen, C
Kristopher, KW
Manna, SK
Scerba, M
Friedman, FK
Luecke, H
Idle, JR
Gonzalez, FJ
AF Cheng, Jie
Chen, Chi
Kristopher, Krausz W.
Manna, Soumen K.
Scerba, Mike
Friedman, Fred K.
Luecke, Hans
Idle, Jeffrey R.
Gonzalez, Frank J.
TI Identification of 2-Piperidone as a Biomarker of CYP2E1 Activity Through
Metabolomic Phenotyping
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE CYP2E1; biomarker; metabolomics; 2-piperidone; cadaverine
ID CYTOCHROME-P450 2E1; OXIDATIVE STRESS; IN-VIVO; HEPATOTOXICITY;
ACETAMINOPHEN; MOUSE; PHARMACOLOGY; INHIBITION; CATABOLISM; EXPRESSION
AB Cytochrome P450 2E1 (CYP2E1) is a key enzyme in the metabolic activation of many low molecular weight toxicants and also an important contributor to oxidative stress. A noninvasive method to monitor CYP2E1 activity in vivo would be of great value for studying the role of CYP2E1 in chemical-induced toxicities and stress-related diseases. In this study, a mass spectrometrybased metabolomic approach was used to identify a metabolite biomarker of CYP2E1 through comparing the urine metabolomes of wild-type (WT), Cyp2e1-null, and CYP2E1-humanized mice. Metabolomic analysis with multivariate models of urine metabolites revealed a clear separation of Cyp2e1-null mice from WT and CYP2E1-humanized mice in the multivariate models of urine metabolomes. Subsequently, 2-piperidone was identified as a urinary metabolite that inversely correlated to the CYP2E1 activity in the three mouse lines. Backcrossing of WT and Cyp2e1-null mice, together with targeted analysis of 2-piperidone in mouse serum, confirmed the genotype dependency of 2-piperidone. The accumulation of 2-piperidone in the Cyp2e1-null mice was mainly caused by the changes in the biosynthesis and degradation of 2-piperidone because compared with the WT mice, the conversion of cadaverine to 2-piperidone was higher, whereas the metabolism of 2-piperidone to 6-hydroxy-2-piperidone was lower in the Cyp2e1-null mice. Overall, untargeted metabolomic analysis identified a correlation between 2-piperidone concentrations in urine and the expression and activity of CYP2E1, thus providing a noninvasive metabolite biomarker that can be potentially used in to monitor CYP2E1 activity.
C1 [Cheng, Jie; Chen, Chi; Kristopher, Krausz W.; Manna, Soumen K.; Friedman, Fred K.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Chen, Chi] Univ Minnesota, Dept Food Sci & Nutr, St Paul, MN 55108 USA.
[Scerba, Mike; Luecke, Hans] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Idle, Jeffrey R.] Univ Bern, Dept Clin Res, Hepatol Res Grp, CH-3010 Bern, Switzerland.
RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, Bldg 37,Room 3106, Bethesda, MD 20892 USA.
EM fjgonz@helix.nih.gov
RI Friedman, Fred/D-4208-2016;
OI Idle, Jeff/0000-0002-6143-1520
FU National Cancer Institute Intramural Research Program
FX National Cancer Institute Intramural Research Program.
NR 35
TC 3
Z9 3
U1 1
U2 20
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
J9 TOXICOL SCI
JI Toxicol. Sci.
PD SEP
PY 2013
VL 135
IS 1
BP 37
EP 47
DI 10.1093/toxsci/kft143
PG 11
WC Toxicology
SC Toxicology
GA 207SQ
UT WOS:000323624500004
PM 23811823
ER
PT J
AU Yeo, L
Romero, R
AF Yeo, Lami
Romero, Roberto
TI Fetal Intelligent Navigation Echocardiography (FINE): a novel method for
rapid, simple, and automatic examination of the fetal heart
SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY
LA English
DT Article
DE 4D; cardiac; congenital heart disease; fetal heart; prenatal diagnosis;
spatiotemporal image correlation; STIC; ultrasound; Virtual Intelligent
Sonographer Assistance; VIS-Assistance (R)
ID SPATIOTEMPORAL IMAGE CORRELATION; STANDARD CARDIAC VIEWS;
PRENATAL-DIAGNOSIS; 4-DIMENSIONAL ULTRASOUND; OUTFLOW TRACTS;
GREAT-ARTERIES; 3-DIMENSIONAL ULTRASOUND; INVERSION MODE; 4-CHAMBER
VIEW; INTERNET LINK
AB Objective To describe a novel method (Fetal Intelligent Navigation Echocardiography (FINE)) for visualization of standard fetal echocardiography views from volume datasets obtained with spatiotemporal image correlation (STIC) and application of intelligent navigation' technology.
Methods We developed a method to: 1) demonstrate nine cardiac diagnostic planes; and 2) spontaneously navigate the anatomy surrounding each of the nine cardiac diagnostic planes (Virtual Intelligent Sonographer Assistance (VIS-Assistance (R))). The method consists of marking seven anatomical structures of the fetal heart. The following echocardiography views are then automatically generated: 1) four chamber; 2) five chamber; 3) left ventricular outflow tract; 4) short-axis view of great vessels/right ventricular outflow tract; 5) three vessels and trachea; 6) abdomen/stomach; 7) ductal arch; 8) aortic arch; and 9) superior and inferior vena cava. The FINE method was tested in a separate set of 50 STIC volumes of normal hearts (18.6-37.2weeks of gestation), and visualization rates for fetal echocardiography views using diagnostic planes and/or VIS-Assistance (R) were calculated. To examine the feasibility of identifying abnormal cardiac anatomy, we tested the method in four cases with proven congenital heart defects (coarctation of aorta, tetralogy of Fallot, transposition of great vessels and pulmonary atresia with intact ventricular septum).
Results In normal cases, the FINE method was able to generate nine fetal echocardiography views using: 1) diagnostic planes in 78-100% of cases; 2) VIS-Assistance (R) in 98-100% of cases; and 3) a combination of diagnostic planes and/or VIS-Assistance (R) in 98-100% of cases. In all four abnormal cases, the FINE method demonstrated evidence of abnormal fetal cardiac anatomy.
Conclusions The FINE method can be used to visualize nine standard fetal echocardiography views in normal hearts by applying intelligent navigation' technology to STIC volume datasets. This method can simplify examination of the fetal heart and reduce operator dependency. The observation of abnormal echocardiography views in the diagnostic planes and/or VIS-Assistance (R) should raise the index of suspicion for congenital heart disease. Published 2013. This article is a U.S. Government work and is in the public domain in the USA
C1 [Yeo, Lami; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Yeo, Lami; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Yeo, Lami] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
[Yeo, Lami; Romero, Roberto] Hutzel Womens Hosp, Detroit Med Ctr, Detroit, MI 48201 USA.
RP Yeo, L (reprint author), Hutzel Womens Hosp, Perinatol Res Branch, NICHD, NIH,DHHS, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM lyeo@med.wayne.edu; romeror@mail.nih.gov
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, NIH, DHHS; Medge Platforms, Inc., New York, NY, USA;
Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Department of Health and
Human Services (NICHD/NIH); Federal funds from NICHD, NIH
[HHSN275201300006C]
FX The work of Dr Roberto Romero was supported by the Perinatology Research
Branch, Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, NIH, DHHS. Dr Roberto
Romero has contributed to this work as part of his official duties as an
employee of the United States Federal Government. Dr Lami Yeo was funded
by Wayne State University through a service contract in support of the
Perinatology Research Branch. The contributions of Mr Abella and Mr
Gayoso were funded by Medge Platforms, Inc., New York, NY, USA.; This
research was supported, in part, by the Perinatology Research Branch,
Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health, Department of Health and Human Services (NICHD/NIH); and, in
part, with Federal funds from NICHD, NIH under Contract No.
HHSN275201300006C.
NR 106
TC 16
Z9 22
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0960-7692
J9 ULTRASOUND OBST GYN
JI Ultrasound Obstet. Gynecol.
PD SEP
PY 2013
VL 42
IS 3
BP 268
EP 284
DI 10.1002/uog.12563
PG 17
WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine &
Medical Imaging
SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine &
Medical Imaging
GA 209HJ
UT WOS:000323746000005
PM 24000158
ER
PT J
AU Funk, EK
Shaffer, A
Shivakumar, B
Sneller, M
Polis, MA
Masur, H
Heytens, L
Nelson, A
Kwan, R
Kottilil, S
Kohli, A
AF Funk, Emily K.
Shaffer, Ashton
Shivakumar, Bhavana
Sneller, Michael
Polis, Michael A.
Masur, Henry
Heytens, Laura
Nelson, Amy
Kwan, Richard
Kottilil, Shyam
Kohli, Anita
TI Short Communication: Interferon/Ribavirin Treatment for HCV Is
Associated with the Development of Hypophosphatemia in HIV/Hepatitis C
Virus-Coinfected Patients
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; TENOFOVIR DISOPROXIL FUMARATE;
HIV-INFECTED PATIENTS; CHRONIC HEPATITIS-C; PLUS RIBAVIRIN;
NATURAL-HISTORY; LIVER FIBROSIS; THERAPY; PROGRESSION; PREVALENCE
AB One-third of all HIV-infected individuals in the United States are estimated to be coinfected with the hepatitis C virus (HCV). Treatment of chronic hepatitis C in patients coinfected with HIV is a complex problem associated with toxicities and drug interactions between HIV antiretrovirals and interferon and ribavirin. In recent HCV treatment studies, we observed a previously unreported development of hypophosphatemia in HIV/HCV-coinfected patients treated with interferon/ribavirin (IFN/RBV). To further investigate this observation, we retrospectively reviewed 61 HIV/HCV-coinfected patients on antiretrovirals (ARVs) during treatment with IFN/RBV as well as 154 HIV-infected patients treated with ARVs alone. We found that HIV/HCV-coinfected patients on IFN/RBV therapy were more likely to develop frequent (57% vs. 13%, IFN/RBV-treated patients vs. no IFN/RBV; chi(2) = 0.001) and higher-grade hypophosphatemia (67.0% Grade 2, 33.3% Grade 3 vs. 94.7% Grade 2, 5.3% Grade 3, IFN/RBV-treated patients vs. no IFN/RBV; chi(2) < 0.001) than untreated patients. In addition, we found that the new onset of hypophosphatemia after IFN/RBV treatment initiation was followed by a diminished frequency of this toxicity upon cessation of IFN/RBV, supporting the idea that a drug-drug interaction may increase the risk of this toxicity. To understand the risks of developing this toxicity, we evaluated the association between individual ARV use and hypophosphatemia incidence. Our data suggest that concomitant tenofovir (TDF) use may be a risk factor for the development of hypophosphatemia in HIV/HCV-coinfected patients treated with IFN/RBV. Although the etiology of this abnormality is likely multifactorial, clinicians should be aware of hypophosphatemia as a potential marker of renal toxicity in HIV/HCV-coinfected patients being treated with IFN/RBV regimens.
C1 [Funk, Emily K.; Shaffer, Ashton; Shivakumar, Bhavana; Sneller, Michael; Polis, Michael A.; Heytens, Laura; Nelson, Amy; Kwan, Richard; Kottilil, Shyam; Kohli, Anita] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Masur, Henry] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Kohli, Anita] SAIC Frederick Inc, Clin Res Directorate CMRP, Frederick Natl Lab Canc Res, Frederick, MD USA.
RP Kohli, A (reprint author), NIAID, NIH, 10 Ctr Dr,Bldg 10-11C442, Bethesda, MD 20892 USA.
EM kohlia@niaid.nih.gov
OI Polis, Michael/0000-0002-9151-2268
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
contract no. HHSN261200800001E. The data were presented in part at CROI
2012 in Seattle, WA.
NR 26
TC 7
Z9 7
U1 0
U2 3
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD SEP
PY 2013
VL 29
IS 9
BP 1190
EP 1194
DI 10.1089/aid.2013.0035
PG 5
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 204NL
UT WOS:000323372600002
PM 23701022
ER
PT J
AU Manuel, SL
Sehgal, M
Khan, ZK
Goedert, JJ
Betts, MR
Jain, P
AF Manuel, Sharron L.
Sehgal, Mohit
Khan, Zafar K.
Goedert, James J.
Betts, Michael R.
Jain, Pooja
TI An Altered Maturation and Adhesion Phenotype of Dendritic Cells in
Diseased Individuals Compared to Asymptomatic Carriers of Human T Cell
Leukemia Virus Type 1
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID HTLV-I INFECTION; FLOW-CYTOMETRY; PD-1 BLOCKADE; RHESUS MACAQUES; TAX
PROTEIN; EXPRESSION; HIV; BLOOD; LYMPHOCYTES; ACTIVATION
AB The immunopathogenic mechanisms underlying human T cell leukemia virus type 1 (HTLV-1)-mediated diseases such as adult T cell leukemia (ATL) and HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) are not clearly understood. As critical effectors of antiviral immune response, dendritic cells (DCs) are implicated to play an important role in determining the outcome of HTLV-1 infection. However, a complete understanding of their role in any disease pathogenesis requires extensive assessment of the phenotypic and functional state of DCs. To enable this, we developed a polychromatic antibody cocktail comprising key phenotypic and functional markers of DCs and applied it in a patient cohort from the HTLV-1 endemic region, Jamaica, consisted of seronegative controls, asymptomatic carriers (ACs), ATL, and HAM/TSP patients. This ex vivo analyses included two major subsets of blood DCs, myeloid and plasmacytoid (mDCs and pDCs, respectively). The comparative analyses of results demonstrated a decreased pDC frequency in both ATL and HAM/TSP patients as compared to ACs and seronegative controls. Similarly, CD86 expression on both mDCs and pDCs was significantly higher in HAM/TSP (but not ATL) patients compared to ACs. Interestingly, HLA-DR expression was significantly lower on pDCs of patients as compared to carriers; however, for mDCs, only the HAM/TSP group had significantly lower expression of HLA-DR. Unlike HAM/TSP individuals, ATL individuals had higher HLA-ABC expression on mDCs compared to ACs. Finally, both mDCs and pDCs of HAM/ TSP patients had significantly higher expression of the programmed death ligand 1 (PD-L1) compared to ACs. Overall, this study suggests that DCs exhibit a differential phenotypic and functional profile between patients (ATL and HAM/TSP) and carriers of HTLV-1 and could provide an important tool for understanding HTLV-1 immunopathogenesis during infection and disease.
C1 [Manuel, Sharron L.; Sehgal, Mohit; Khan, Zafar K.; Jain, Pooja] Drexel Univ, Coll Med, Dept Microbiol & Immunol, Philadelphia, PA 19104 USA.
[Manuel, Sharron L.; Sehgal, Mohit; Khan, Zafar K.; Jain, Pooja] Drexel Univ, Coll Med, Drexel Inst Biotechnol & Virol, Philadelphia, PA 19104 USA.
[Goedert, James J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Betts, Michael R.] Univ Penn, Sch Med, Dept Microbiol & Immunol, Philadelphia, PA 19104 USA.
RP Jain, P (reprint author), Drexel Univ, Coll Med, Dept Microbiol & Immunol, 3805 Old Easton Rd, Doylestown, PA 18902 USA.
EM pjain@drexelmed.edu
FU Public Health Service, National Institutes of Health; NIAID [R01
AI077414, R21 AI 093172-01]; NCI [R01 CA054559]; Philadelphia NeuroAIDS
Training Grant [T32 MH079785]
FX This work was supported by the Public Health Service, National
Institutes of Health, wherein P.J. was funded through NIAID R01 AI077414
and NCI R01 CA054559 while Z.K.K. was funded through NIAID R21 AI
093172-01. In addition, we thank the Philadelphia NeuroAIDS Training
Grant T32 MH079785 that has supported the efforts of S. Manuel.
NR 53
TC 4
Z9 4
U1 0
U2 5
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD SEP
PY 2013
VL 29
IS 9
BP 1273
EP 1285
DI 10.1089/aid.2013.0054
PG 13
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 204NL
UT WOS:000323372600015
PM 23750452
ER
PT J
AU White, CL
Pergola, PE
Szychowski, JM
Talbert, R
Cervantes-Arriaga, A
Clark, HD
Del Brutto, OH
Godoy, IE
Hill, MD
Pelegri, A
Sussman, CR
Taylor, AA
Valdivia, J
Anderson, DC
Conwit, R
Benavente, OR
AF White, Carole L.
Pergola, Pablo E.
Szychowski, Jeff M.
Talbert, Robert
Cervantes-Arriaga, Amin
Clark, Heather D.
Del Brutto, Oscar H.
Esteban Godoy, Ivan
Hill, Michael D.
Pelegri, Antoni
Sussman, Craig R.
Taylor, Addison A.
Valdivia, Jose
Anderson, Dave C.
Conwit, Robin
Benavente, Oscar R.
CA SPS3 Investigators
TI Blood Pressure After Recent Stroke: Baseline Findings From the Secondary
Prevention of Small Subcortical Strokes Trial
SO AMERICAN JOURNAL OF HYPERTENSION
LA English
DT Article
DE blood pressure control; blood pressure; ethnicity; hypertension;
ischemic stroke; lacunar stroke; risk factors; stroke prevention; white
matter disease
ID CONVERTING-ENZYME-INHIBITOR; TRANSIENT ISCHEMIC ATTACK; RECURRENT
STROKE; RANDOMIZED TRIAL; LOWERING REGIMEN; UNITED-STATES; HYPERTENSION;
RISK; MANAGEMENT; GUIDELINES
AB BACKGROUND
Hypertension is the most powerful risk factor for stroke. The aim of this study was to characterize baseline blood pressure in participants in the Secondary Prevention of Small Subcortical Strokes trial.
METHODS
For this cross-sectional analysis, participants were categorized by baseline systolic blood pressure (SBP) < 120, 120-139, 140-159, 160-179, and 180 mm Hg and compared on demographic and clinical characteristics. Predictors of SBP < 140 mm Hg were examined.
RESULTS
Mean SBP was 143 +/- 19 mm Hg while receiving an average of 1.7 antihypertensive medications; SBP >= 140 mm Hg for 53% and >= 160 mm Hg for 18% of the 3,020 participants. Higher SBP was associated with a history of hypertension and hypertension for longer duration (both P < 0.0001). Higher SBPs were associated with more extensive white matter disease on magnetic resonance imaging (P < 0.0001). There were significant differences in entry-level SBP when participants were categorized by race and region (both P < 0.0001). Black participants were more likely to have SBP >= 140 mm Hg. Multivariable logistic regression showed an independent effect for region with those from Canada more likely (odds ratio = 1.7; 95% confidence interval, 1.29, 2.32) to have SBP < 140 mm Hg compared with participants from United States.
CONCLUSIONS
In this cohort with symptomatic lacunar stroke, more than half had uncontrolled hypertension at approximately 2.5 months after stroke. Regional, racial, and clinical differences should be considered to improve control and prevent recurrent stroke.
C1 [White, Carole L.] Univ Texas Hlth Sci Ctr San Antonio, Sch Nursing, San Antonio, TX 78229 USA.
[Pergola, Pablo E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.
[Pergola, Pablo E.] Renal Associates PA, San Antonio, TX USA.
[Szychowski, Jeff M.] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA.
[Talbert, Robert] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA.
[Cervantes-Arriaga, Amin] Natl Inst Neurol & Neurosurg, Neurodegenerat Res Unit, Mexico City, DF, Mexico.
[Clark, Heather D.] Univ Ottawa, Dept Med, Ottawa, ON, Canada.
[Clark, Heather D.] Ottawa Hosp, Ottawa, ON, Canada.
[Del Brutto, Oscar H.] Hosp Clin Kennedy, Dept Neurol Sci, Guayaquil, Ecuador.
[Esteban Godoy, Ivan] Pontificia Univ Catolica Chile, Dept Med, Santiago, Chile.
[Hill, Michael D.] Univ Calgary, Hotchkiss Brain Inst, Dept Clin Neurosci, Calgary, AB, Canada.
[Pelegri, Antoni] Hosp Sagrat Cor, Dept Nephrol, Barcelona, Spain.
[Sussman, Craig R.] Vanderbilt Univ, Med Ctr, Div Gen Internal Med, Nashville, TN USA.
[Sussman, Craig R.] Vanderbilt Univ, Med Ctr, Div Endocrinol Metab, Nashville, TN USA.
[Taylor, Addison A.] Baylor Coll Med, Dept Med, Div Hypertens & Clin Pharmacol, Sect Cardiovasc Res, Houston, TX 77030 USA.
[Valdivia, Jose] Hosp Alberto Sabogal, Dept Med, Lima, Peru.
[Anderson, Dave C.] Univ Minnesota, Sch Med, Hennepin Cty Med Ctr, Minneapolis, MN 55455 USA.
[Conwit, Robin] NINDS, Off Clin Res, Bethesda, MD 20892 USA.
[Benavente, Oscar R.] Univ British Columbia, Dept Med, Div Neurol, Brain Res Ctr, Vancouver, BC V6T 1W5, Canada.
RP Pergola, PE (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.
EM ppergola@raparesearch.com
RI Hill, Michael/C-9073-2012
OI Hill, Michael/0000-0002-6269-1543
FU National Institute of Neurological Disorders and Stroke [2 U01
NS38529-04A1]
FX The SPS3 study was funded by the National Institute of Neurological
Disorders and Stroke (2 U01 NS38529-04A1). We gratefully acknowledge the
contributions of the SPS3 investigators and coordinators.
NR 38
TC 11
Z9 11
U1 0
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0895-7061
J9 AM J HYPERTENS
JI Am. J. Hypertens.
PD SEP
PY 2013
VL 26
IS 9
BP 1114
EP 1122
DI 10.1093/ajh/hpt076
PG 9
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 203NB
UT WOS:000323298800009
PM 23736109
ER
PT J
AU Yabroff, KR
Short, PF
Machlin, S
Dowling, E
Rozjabek, H
Li, CY
McNeel, T
Ekwueme, DU
Virgo, KS
AF Yabroff, K. Robin
Short, Pamela F.
Machlin, Steven
Dowling, Emily
Rozjabek, Heather
Li, Chunyu
McNeel, Timothy
Ekwueme, Donatus U.
Virgo, Katherine S.
TI Access to Preventive Health Care for Cancer Survivors
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID 2ND PRIMARY CANCERS; UNITED-STATES; MEDICAL-CARE; BREAST; MAINTENANCE
AB Background: Access to health care, particularly effective primary and secondary preventive care, is critical for cancer survivors, in order to minimize the adverse sequelae of cancer and its treatment.
Purpose: The goal of the study was to evaluate the association between cancer survivorship and access to primary and preventive health care.
Methods: Cancer survivors (n=4960) and individuals without a cancer history (n=64,431) aged >= 18 years, from the 2008-2010 Medical Expenditure Panel Survey (MEPS), were evaluated. Multiple measures of access and preventive services use were compared. The association between cancer survivorship and access and preventive services was evaluated with multivariate logistic regression models, stratified by age group (18-64 years and >= 65 years), controlling for the effects of age, gender, race/ethnicity, education, marital status, and comorbidities. Data were analyzed in 2013.
Results: Cancer survivors aged >= 65 years had equivalent or greater access and preventive services use than individuals without a cancer history, in adjusted analyses. However, among those aged 18-64 years with private health insurance, cancer survivors were more likely than other individuals to have a usual source of care and to use preventive services, whereas uninsured or publicly insured cancer survivors were generally less likely to have a usual source of care and to use preventive services than were uninsured or publicly insured adults without a cancer history.
Conclusions: Although access and preventive care use in cancer survivors is generally equivalent or greater compared to that of other individuals, disparities for uninsured and publicly insured cancer survivors aged 18-64 years suggest that improvements in survivor care are needed. Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine
C1 [Yabroff, K. Robin; Rozjabek, Heather] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Machlin, Steven] Agcy Healthcare Res & Qual, Ctr Financing Access & Cost Trends, Rockville, MD USA.
[McNeel, Timothy] Informat Management Serv Inc, Calverton, MD USA.
[Short, Pamela F.] Penn State Univ, Ctr Hlth Care & Policy Res, University Pk, PA 16802 USA.
[Dowling, Emily] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA.
[Li, Chunyu; Ekwueme, Donatus U.] CDC, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA.
[Virgo, Katherine S.] Intramural Res Dept, Hlth Serv Res Program, Amer Canc Soc, Natl Home Off, Atlanta, GA USA.
RP Yabroff, KR (reprint author), NCI, Hlth Serv & Econ Branch, 9609 Med Ctr Dr,3E436, Rockville, MD 20850 USA.
EM yabroffr@mail.nih.gov
NR 28
TC 10
Z9 10
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD SEP
PY 2013
VL 45
IS 3
BP 304
EP 312
DI 10.1016/j.amepre.2013.04.021
PG 9
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 202CU
UT WOS:000323191900008
ER
PT J
AU Gorelick, DA
Goodwin, RS
Schwilke, E
Schroeder, JR
Schwope, DM
Kelly, DL
Ortemann-Renon, C
Bonnet, D
Huestis, MA
AF Gorelick, David A.
Goodwin, Robert S.
Schwilke, Eugene
Schroeder, Jennifer R.
Schwope, David M.
Kelly, Deanna L.
Ortemann-Renon, Catherine
Bonnet, Denis
Huestis, Marilyn A.
TI Around-the-clock oral THC effects on sleep in male chronic daily
cannabis smokers
SO AMERICAN JOURNAL ON ADDICTIONS
LA English
DT Article
ID ADMINISTERED DELTA-9-TETRAHYDROCANNABINOL; MARIJUANA; HUMANS; ADULTS
AB Background and Objectives: Delta 9-tetrahydrocannabinol (THC) promotes sleep in animals; clinical use of THC is associated with somnolence. Human laboratory studies of oral THC have not shown consistent effects on sleep. We prospectively evaluated self-reported sleep parameters during controlled oral THC administration to research volunteers.
Methods: Thirteen male chronic daily cannabis smokers (mean +/- SD age 24.6 +/- 3.7 years, self-reported smoking frequency of 5.5 +/- 5.9 (range 1-24) joint-equivalents daily at study entry) were administered oral THC doses (20 mg) around-the-clock for 7 days (40-120 mg daily) starting the afternoon after admission. The St. Mary's Hospital Sleep Questionnaire was completed every morning. Plasma THC and 11-OH-THC (active metabolite) concentrations were measured in venous blood samples collected every evening. Changes in sleep characteristics over time and associations between sleep characteristics and plasma cannabinoid concentrations were evaluated with repeated measures mixed linear regression.
Results: Higher evening THC and 11-OH-THC concentrations were significantly associated with shorter sleep latency, less difficulty falling asleep, and more daytime sleep the following day. In contrast, the duration of calculated and self-reported nighttime sleep decreased slightly (3.54 and 5.34 minutes per night, respectively) but significantly during the study.
Conclusions: These findings suggest that tolerance to the somnolent effects of THC may have occurred, but results should be considered preliminary due to design limitations.
Scientific Significance: Somnolence from oral THC may dissipate with chronic, high-dose use. This has implications for patients who may take chronic oral THC for medicinal purposes, including cannabis dependence treatment.
C1 [Gorelick, David A.; Goodwin, Robert S.; Schwilke, Eugene; Schwope, David M.; Huestis, Marilyn A.] NIDA, Chem & Drug Metab Sect, NIH, Baltimore, MD 21224 USA.
[Schroeder, Jennifer R.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Kelly, Deanna L.] Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA.
[Ortemann-Renon, Catherine; Bonnet, Denis] Sanofi Aventis Rech, Montpellier, France.
RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab Sect, IRP, NIH, 251 Bayview Blvd,Room 05A721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU Intramural NIH HHS [Z01 DA000414-10, Z01 DA000414-11, Z01 DA000415-10,
Z01 DA000415-11]
NR 19
TC 7
Z9 7
U1 0
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1055-0496
J9 AM J ADDICTION
JI Am. J. Addict.
PD SEP
PY 2013
VL 22
IS 5
BP 510
EP 514
DI 10.1111/j.1521-0391.2013.12003.x
PG 5
WC Substance Abuse
SC Substance Abuse
GA 202DV
UT WOS:000323194600014
PM 23952899
ER
PT J
AU Liu, W
Harman, MP
Hancock, C
Phang, JM
AF Liu, Wei
Harman, Meredith P.
Hancock, Chad
Phang, James M.
TI The control of proline metabolism in cancers by oncogenic and tumor
suppressor signalings
SO AMINO ACIDS
LA English
DT Meeting Abstract
C1 [Liu, Wei; Harman, Meredith P.; Hancock, Chad; Phang, James M.] NCI, Metab & Canc Susceptibil Sect, Basic Res Lab, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0939-4451
J9 AMINO ACIDS
JI Amino Acids
PD SEP
PY 2013
VL 45
IS 3
BP 585
EP 585
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 202JZ
UT WOS:000323212600086
ER
PT J
AU Hancock, CN
Phang, JM
AF Hancock, Chad N.
Phang, James M.
TI Effects of co-regulation of proline oxidase and succinate dehydrogenase
on mitochondrial respiration
SO AMINO ACIDS
LA English
DT Meeting Abstract
C1 [Hancock, Chad N.; Phang, James M.] Frederick Natl Lab Canc Res, Basic Res Lab, Metab & Canc Susceptibil Sect, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 5
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0939-4451
J9 AMINO ACIDS
JI Amino Acids
PD SEP
PY 2013
VL 45
IS 3
BP 593
EP 593
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 202JZ
UT WOS:000323212600112
ER
PT J
AU Louis, JF
Thoma, ME
Sorensen, DN
McLain, AC
King, RB
Sundaram, R
Keiding, N
Louis, GMB
AF Louis, J. F.
Thoma, M. E.
Sorensen, D. N.
McLain, A. C.
King, R. B.
Sundaram, R.
Keiding, N.
Louis, G. M. Buck
TI The prevalence of couple infertility in the United States from a male
perspective: evidence from a nationally representative sample
SO ANDROLOGY
LA English
DT Article
ID CURRENT-DURATION APPROACH; TIME-TO-PREGNANCY; SEMEN QUALITY; TESTICULAR
CANCER; OLDER MEN; FERTILITY; AGE; POPULATION; FECUNDITY; HEALTH
AB Infertility is a couple-based fecundity impairment, although population level research is largely based upon information reported by female partners. Of the few studies focusing on male partners, most focus on the utilization of infertility services rather than efforts to estimate the prevalence and determinants of infertility as reported by male partners. Data from a nationally representative sample of men aged 15-44 years who participated in the 2002 National Survey of Family Growth (NSFG) were used to estimate the prevalence of infertility and determinants of longer time-to-pregnancy (TTP) using the novel current duration (CD) approach. Using backward recurrence time parametric survival methods, we estimated infertility prevalence (TTP > 12 months) and time ratios (TR) associated with TTP as derived from males' reported CD of their pregnancy attempt. The estimated prevalence of infertility was 12.0% (95% CI: 7.0, 23.2). Longer TTP was associated with older male age (35-45 vs. 17-24 years) (TR: 2.49; 95% CI: 1.03, 6.03), biological childlessness (TR: 1.53; 95% CI: 1.07, 2.19) and lack of health insurance (TR: 1.73; 95% CI: 1.02, 2.94) after controlling for the differences in couples' age and other socioeconomic factors. The prevalence of infertility based on male reporting is consistent with estimates of infertility in the US found in prospective cohort studies and CD studies based on female reporting. Our findings suggest that male partners can reliably inform about couple infertility. Interventions and services aimed at reducing couple infertility should include attention to male factors associated with longer TTP identified in this study.
C1 [Louis, J. F.; Thoma, M. E.; Sundaram, R.; Louis, G. M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD USA.
[Sorensen, D. N.; Keiding, N.] Univ Copenhagen, Dept Biostat, Copenhagen, Denmark.
[McLain, A. C.] Univ S Carolina, Dept Epidemiol & Biostat, Columbia, SC 29208 USA.
[King, R. B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Populat Dynam Branch, NIH, Rockville, MD USA.
RP Louis, GMB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd Room 7B03, Bethesda, MD 20892 USA.
EM louisg@mail.nih.gov
OI Louis, Jean F/0000-0003-0339-647X; Sundaram,
Rajeshwari/0000-0002-6918-5002; Buck Louis, Germaine/0000-0002-1774-4490
FU U.S. Department of Health and Human Services: Eunice Kennedy Shriver
National Institute for Child Health and Human Development (NICHD);
National Institutes of Health (NIH); Office of Population Affairs; CDC's
National Center for Health Statistics (CDC/NCHS); CDC's Division of
HIV/AIDS Prevention (CDC/DHAP); CDC's Division of Sexually Transmitted
Disease Prevention (CDC/DSTDP); CDC's Division of Reproductive Health
(CDC/DRH); Office of the Assistant Secretary for Planning and Evaluation
(OASPE); Children's Bureau of the Administration for Children and
Families; Intramural Research Program, NICHD, NIH
FX The 2002 NSFG was conducted by the Centers for Disease Control and
Prevention's (CDC) National Center for Health Statistics (NCHS) with the
support and assistance of a number of other organizations and
individuals, with the participation and funding support of the following
programs of the U.S. Department of Health and Human Services: Eunice
Kennedy Shriver National Institute for Child Health and Human
Development (NICHD), National Institutes of Health (NIH), Office of
Population Affairs, CDC's National Center for Health Statistics
(CDC/NCHS), CDC's Division of HIV/AIDS Prevention (CDC/DHAP), CDC's
Division of Sexually Transmitted Disease Prevention (CDC/DSTDP), CDC's
Division of Reproductive Health (CDC/DRH), Office of the Assistant
Secretary for Planning and Evaluation (OASPE), Children's Bureau of the
Administration for Children and Families. The analysis and writing of
this paper was supported by the Intramural Research Program, NICHD, NIH.
NR 47
TC 40
Z9 40
U1 1
U2 19
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-2919
J9 ANDROLOGY-US
JI Andrology
PD SEP
PY 2013
VL 1
IS 5
BP 741
EP 748
DI 10.1111/j.2047-2927.2013.00110.x
PG 8
WC Andrology
SC Endocrinology & Metabolism
GA 204RJ
UT WOS:000323385700011
PM 23843214
ER
PT J
AU Moayeri, M
Crown, D
Jiao, GS
Kim, S
Johnson, A
Leysath, C
Leppla, SH
AF Moayeri, Mahtab
Crown, Devorah
Jiao, Guan-Sheng
Kim, Seongjin
Johnson, Alan
Leysath, Clinton
Leppla, Stephen H.
TI Small-Molecule Inhibitors of Lethal Factor Protease Activity Protect
against Anthrax Infection
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID EDEMA TOXIN; KINASE-KINASE; IDENTIFICATION; DYSFUNCTION; ANTIBODIES;
ANTIDOTES; BARRIER; MODEL; SHOCK; RATS
AB Bacillus anthracis, the causative agent of anthrax, manifests its pathogenesis through the action of two secreted toxins. The bipartite lethal and edema toxins, a combination of lethal factor or edema factor with the protein protective antigen, are important virulence factors for this bacterium. We previously developed small-molecule inhibitors of lethal factor proteolytic activity (LFIs) and demonstrated their in vivo efficacy in a rat lethal toxin challenge model. In this work, we show that these LFIs protect against lethality caused by anthrax infection in mice when combined with subprotective doses of either antibiotics or neutralizing monoclonal antibodies that target edema factor. Significantly, these inhibitors provided protection against lethal infection when administered as a monotherapy. As little as two doses (10 mg/kg) administered at 2 h and 8 h after spore infection was sufficient to provide a significant survival benefit in infected mice. Administration of LFIs early in the infection was found to inhibit dissemination of vegetative bacteria to the organs in the first 32 h following infection. In addition, neutralizing antibodies against edema factor also inhibited bacterial dissemination with similar efficacy. Together, our findings confirm the important roles that both anthrax toxins play in establishing anthrax infection and demonstrate the potential for small-molecule therapeutics targeting these proteins.
C1 [Moayeri, Mahtab; Crown, Devorah; Leysath, Clinton; Leppla, Stephen H.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD USA.
[Jiao, Guan-Sheng; Kim, Seongjin; Johnson, Alan] PanTheraBiopharma LLC, Aiea, HI USA.
RP Moayeri, M (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD USA.
EM mmoayeri@niaid.nih.gov
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases; National Institute of Diabetes and Digestive and
Kidney Diseases; NIH [U01 AI078067]
FX This research was supported in part by the Intramural Research Program
of the National Institute of Allergy and Infectious Diseases and the
National Institute of Diabetes and Digestive and Kidney Diseases. A.J.,
G.-S.J., and S. K. are supported by NIH grant U01 AI078067.
NR 38
TC 13
Z9 13
U1 0
U2 10
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
EI 1098-6596
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD SEP
PY 2013
VL 57
IS 9
BP 4139
EP 4145
DI 10.1128/AAC.00941-13
PG 7
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 203IL
UT WOS:000323285500006
PM 23774434
ER
PT J
AU Lin, PL
Coleman, T
Carney, JPJ
Lopresti, BJ
Tomko, J
Fillmore, D
Dartois, V
Scanga, C
Frye, LJ
Janssen, C
Klein, E
Barry, CE
Flynn, JL
AF Lin, Philana Ling
Coleman, Teresa
Carney, Jonathan P. J.
Lopresti, Brian J.
Tomko, Jaime
Fillmore, Dan
Dartois, Veronique
Scanga, Charles
Frye, L. James
Janssen, Christopher
Klein, Edwin
Barry, Clifton E., III
Flynn, JoAnne L.
TI Radiologic Responses in Cynomolgus Macaques for Assessing Tuberculosis
Chemotherapy Regimens
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID POSITRON-EMISSION-TOMOGRAPHY; GAMMA RELEASE ASSAYS;
MYCOBACTERIUM-TUBERCULOSIS; PULMONARY TUBERCULOSIS; THERAPEUTIC
RESPONSE; LATENT TUBERCULOSIS; F-18-FDG PET/CT; ENDEMIC COUNTRY; MURINE
MODEL; FDG PET
AB Trials to test new drugs currently in development against tuberculosis in humans are impractical. All animal models to prioritize new regimens are imperfect, but nonhuman primates (NHPs) infected with Mycobacterium tuberculosis develop active tuberculosis (TB) disease with a full spectrum of lesion types seen in humans. Serial 2-deoxy-2-[F-18]-fluoro-D-glucose (FDG) positron emission tomography (PET) with computed tomography (CT) imaging was performed on cynomolgus macaques during infection and chemotherapy with individual agents or the four-drug combination therapy most widely used globally. The size and metabolic activity of lung granulomas varied among animals and even within a single animal during development of disease. Individual granulomas within untreated animals had highly local and independent outcomes, some progressing in size and FDG uptake, while others waned, illustrating the highly dynamic nature of active TB. At necropsy, even untreated animals were found to have a proportion of sterile lesions consistent with the dynamics of this infection. A more marked reduction in overall metabolic activity in the lungs (decreased FDG uptake) was associated with effective treatment. A reduction in the size of individual lesions correlated with a lower bacterial burden at necropsy. Isoniazid treatment was associated with a transient increase in metabolic activity in individual lesions, whereas a net reduction occurred in most lesions from rifampin-treated animals. Quadruple-drug therapy resulted in the highest decrease in FDG uptake. The findings of PET-CT imaging may provide an important early correlate of the efficacy of novel combinations of new drugs that can be directly translated to human clinical trials.
C1 [Lin, Philana Ling] Univ Pittsburgh, Dept Pediat, Childrens Hosp Pittsburgh, Med Ctr,Sch Med, Pittsburgh, PA 15260 USA.
[Coleman, Teresa; Carney, Jonathan P. J.; Lopresti, Brian J.] Univ Pittsburgh, Dept Radiol, Med Ctr, Pittsburgh, PA 15260 USA.
[Tomko, Jaime; Fillmore, Dan; Scanga, Charles; Flynn, JoAnne L.] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA 15260 USA.
[Dartois, Veronique] Univ Med & Dent New Jersey, Dept Med, Newark, NJ 07103 USA.
[Scanga, Charles; Frye, L. James; Flynn, JoAnne L.] Univ Pittsburgh, Ctr Vaccine Res, Pittsburgh, PA USA.
[Janssen, Christopher; Klein, Edwin] Univ Pittsburgh, Div Lab Anim Res, Pittsburgh, PA USA.
[Barry, Clifton E., III] NIAID, TB Res Sect, NIH, Bethesda, MD 20892 USA.
RP Flynn, JL (reprint author), Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA 15260 USA.
EM joanne@pitt.edu
RI Barry, III, Clifton/H-3839-2012; Lopresti, Brian/O-2465-2016
OI Lopresti, Brian/0000-0002-0595-0203
FU Bill and Melinda Gates Foundation TB Drug Accelerator; Intramural
Research Program of the NIAID, NIH
FX These studies were supported by the Bill and Melinda Gates Foundation TB
Drug Accelerator and (in part) by the Intramural Research Program of the
NIAID, NIH.
NR 35
TC 53
Z9 54
U1 1
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
EI 1098-6596
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD SEP
PY 2013
VL 57
IS 9
BP 4237
EP 4244
DI 10.1128/AAC.00277-13
PG 8
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 203IL
UT WOS:000323285500018
PM 23796926
ER
PT J
AU Thanassoulis, G
Peloso, GM
O'Donnell, CJ
AF Thanassoulis, George
Peloso, Gina M.
O'Donnell, Christopher J.
TI Genomic Medicine for Improved Prediction and Primordial Prevention of
Cardiovascular Disease
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Editorial Material
DE atherosclerosis; cholesterol; genetics; genomics; myocardial infarction;
prediction; prevention; risk
ID CORONARY-HEART-DISEASE; GENETIC RISK SCORE; MENDELIAN RANDOMIZATION;
TRIAL; ASSOCIATION
C1 [Thanassoulis, George] McGill Univ, Ctr Hlth, Montreal, PQ H3A 2T5, Canada.
[Peloso, Gina M.; O'Donnell, Christopher J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[O'Donnell, Christopher J.] Natl Heart Lung & Blood Inst, Framingham, MA USA.
RP O'Donnell, CJ (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM odonnellc@nhlbi.nih.gov
FU Intramural NIH HHS [Z99 HL999999, ZIA HL006002-06]
NR 21
TC 5
Z9 5
U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD SEP
PY 2013
VL 33
IS 9
BP 2049
EP 2050
DI 10.1161/ATVBAHA.113.301814
PG 2
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 203UY
UT WOS:000323320700002
PM 23946465
ER
PT J
AU Altarifi, AA
Rice, KC
Negus, SS
AF Altarifi, Ahmad A.
Rice, Kenner C.
Negus, S. Stevens
TI Abuse-related effects of mu-opioid analgesics in an assay of
intracranial self-stimulation in rats: modulation by chronic morphine
exposure
SO BEHAVIOURAL PHARMACOLOGY
LA English
DT Article
DE chronic morphine; drug abuse; fentanyl; intracranial self-stimulation;
methadone; nalbuphine; rat; tolerance
ID MIXED-ACTION OPIOIDS; CROSS-TOLERANCE; HEALTHY-VOLUNTEERS; FOOD
PRESENTATION; SQUIRREL-MONKEYS; RHESUS-MONKEYS; RECEPTOR; AGONISTS;
SENSITIZATION; WITHDRAWAL
AB Intracranial self-stimulation (ICSS) is an operant procedure in which responding is maintained by electrical brain stimulation. Stimulation frequency can be varied rapidly to maintain a wide range of baseline response rates, and drugs' effects can be evaluated simultaneously on both low ICSS rates maintained by low stimulation frequencies and high ICSS rates maintained by high stimulation frequencies. ICSS facilitation' indicates drug-induced increases in low ICSS rates and is often considered an abuse-related effect, whereas ICSS depression' indicates decreases in high ICSS rates and may indicate abuse-limiting effects. This study examined the roles of mu-agonist efficacy and of previous mu-agonist exposure as determinants of mu-agonist effects on ICSS in rats with electrodes implanted into the medial forebrain bundle. The high-efficacy, intermediate-efficacy, and low-efficacy mu agonists methadone, fentanyl, and nalbuphine were tested during escalating regimens of morphine exposure (vehicle, 3.2, and 18 mg/kg/day). During vehicle treatment, methadone and fentanyl primarily depressed ICSS, whereas nalbuphine produced weak facilitation that was not dose dependent. Chronic morphine produced tolerance to ICSS depression and increased expression of ICSS facilitation. These results suggest that mu-agonist exposure increases the expression of abuse-related ICSS facilitation by mu agonists with a broad range of efficacies at mu receptors.
C1 [Altarifi, Ahmad A.; Negus, S. Stevens] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA.
[Rice, Kenner C.] NIAAA, Chem Biol Res Branch, NIDA, Bethesda, MD USA.
[Altarifi, Ahmad A.] Jordan Univ Sci & Technol, Fac Med, Irbid, Jordan.
RP Negus, SS (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, 410 North 12th St,POB 980613, Richmond, VA 23298 USA.
EM ssnegus@vcu.edu
FU NIH [R01-NS070715, T32-DA007027]; National Institute on Drug Abuse;
National Institute on Alcohol Abuse and Alcoholism
FX This research was supported by NIH grants R01-NS070715 and T32-DA007027
and by training support from the Jordan University of Science and
Technology. A portion of this work was also supported by the Intramural
Research Programs of the National Institute on Drug Abuse and the
National Institute on Alcohol Abuse and Alcoholism.
NR 43
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U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0955-8810
J9 BEHAV PHARMACOL
JI Behav. Pharmacol.
PD SEP
PY 2013
VL 24
IS 5-6
BP 459
EP 470
DI 10.1097/FBP.0b013e328364c0bd
PG 12
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA 202NX
UT WOS:000323225500013
PM 23881045
ER
PT J
AU Comer, SD
Metz, VE
Cooper, ZD
Kowalczyk, WJ
Jones, JD
Sullivan, MA
Manubay, JM
Vosburg, SK
Smith, ME
Peyser, D
Saccone, PA
AF Comer, Sandra D.
Metz, Verena E.
Cooper, Ziva D.
Kowalczyk, William J.
Jones, Jermaine D.
Sullivan, Maria A.
Manubay, Jeanne M.
Vosburg, Suzanne K.
Smith, Mary E.
Peyser, Deena
Saccone, Phillip A.
TI Comparison of a drug versus money and drug versus drug
self-administration choice procedure with oxycodone and morphine in
opioid addicts
SO BEHAVIOURAL PHARMACOLOGY
LA English
DT Article
DE abuse liability; buprenorphine maintenance; human; morphine : oxycodone
ratio; opioid dependence; physiological and subjective effects;
self-administration procedure
ID BUPRENORPHINE-NALOXONE; INTRANASAL HEROIN; MAINTAINED HUMANS; PAIN
MANAGEMENT; DEPENDENCE; ABUSE; ANALGESICS
AB This double-blind, placebo-controlled study investigated the effects of oral morphine (0, 45, 135 mg/70 kg) and oral oxycodone (0, 15, 45 mg/70 kg) on buprenorphine-maintained opioid addicts. As a 3 : 1 morphine : oxycodone oral dose ratio yielded equivalent subjective and physiological effects in nondependent individuals, this ratio was used in the present study. Two self-administration laboratory procedures - that is, a drug versus money and a drug versus drug procedure - were assessed. Study participants (N=12) lived in the hospital and were maintained on 4 mg/day sublingual buprenorphine. When participants chose between drug and money, money was preferred over all drug doses; only high-dose oxycodone was self-administered more than placebo. When participants chose between drug and drug, both drugs were chosen more than placebo, high doses of each drug were chosen over low doses, and high-dose oxycodone was preferred over high-dose morphine. The subjective, performance-impairing, and miotic effects of high-dose oxycodone were generally greater than those of high-dose morphine. The study demonstrated that a 3 : 1 oral dose ratio of morphine : oxycodone was not equipotent in buprenorphine-dependent individuals. Both self-administration procedures were effective for assessing the relative reinforcing effects of drugs; preference for one procedure should be driven by the specific research question of interest.
C1 [Comer, Sandra D.; Metz, Verena E.; Cooper, Ziva D.; Jones, Jermaine D.; Sullivan, Maria A.; Manubay, Jeanne M.; Vosburg, Suzanne K.; Smith, Mary E.; Peyser, Deena] Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Dept Psychiat, Div Substance Abuse, New York, NY 10032 USA.
[Kowalczyk, William J.] NIDA, NIH, IRP,Clin Pharmacol & Therapeut Branch, Nicotine Pharmacol Sect, Baltimore, MD USA.
[Saccone, Phillip A.] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA.
RP Comer, SD (reprint author), Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Dept Psychiat, Div Substance Abuse, 1051 Riverside Dr,Unit 120, New York, NY 10032 USA.
EM sdc10@columbia.edu
RI Cooper, Ziva/L-2009-2014;
OI Kowalczyk, William/0000-0001-8026-285X
FU NIDA [DA09236]
FX The authors gratefully acknowledge NIDA for providing funding for this
study (DA09236). NIDA had no role in study design or in the decision to
submit the paper for publication. NIDA also had no role in the
collection, analysis, and interpretation of data or in the writing of
the report. The authors thank Drs Jennifer Hanner, Benjamin Nordstrom,
Shabnam Shakibaie, and Soteri Polydorou for providing medical coverage
during laboratory sessions and participant screening. In addition, they
thank Janet Murray, RN, and Claudia Tindall, NP, for providing nursing
support during the study. Portions of these data were presented at the
2007 and 2009 meetings of the College on Problems of Drug Dependence.
NR 21
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U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0955-8810
J9 BEHAV PHARMACOL
JI Behav. Pharmacol.
PD SEP
PY 2013
VL 24
IS 5-6
BP 504
EP 516
DI 10.1097/FBP.0b013e328363d1c4
PG 13
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA 202NX
UT WOS:000323225500019
PM 23839029
ER
PT J
AU Galski, H
Oved-Gelber, T
Simanovsky, M
Lazarovici, P
Gottesman, MM
Nagler, A
AF Galski, Hanan
Oved-Gelber, Tamar
Simanovsky, Masha
Lazarovici, Philip
Gottesman, Michael M.
Nagler, Arnon
TI P-glycoprotein-dependent resistance of cancer cells toward the extrinsic
TRAIL apoptosis signaling pathway
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE Apoptosis; P-glycoprotein; TRAIL; Resistance; Modulators
ID MULTIDRUG-RESISTANCE; IMMUNE-SYSTEM; HEMATOLOGICAL MALIGNANCIES; DEATH
RECEPTOR; THERAPEUTICS; CYTOTOXICITY; ACTIVATION; EXPRESSION; REVERSAL;
ANTIBODY
AB The TNF-related apoptosis-inducing ligand (TRAIL or Apo2L) preferentially cause apoptosis of malignant cells in vitro and in vivo without severe toxicity. Therefore, TRAIL or agonist antibodies to the TRAIL DR4 and DR5 receptors are used in cancer therapy. However, many malignant cells are intrinsically-resistant or acquire resistance to TRAIL. It has been previously proposed that the multidrug transporter P-glycoprotein (Pgp) might play a role in resistance of cells to intrinsic apoptotic pathways by interfering with components of ceramide metabolism or by modulating the electrochemical gradient across the plasma membrane. In this study we investigated whether Pgp also confers resistance toward extrinsic death ligands of the TNF family. To this end we focused our study on HeLa cells carrying a tetracycline-repressible plasmid system which shuts down Pgp expression in the presence of tetracycline. Our findings demonstrate that expression of Pgp is a significant factor conferring resistance to TRAIL administration, but not to other death ligands such as TNF-alpha. and Fas ligand. Moreover, blocking Pgp transport activity sensitizes the malignant cells toward TRAIL. Therefore, Pgp transport function is required to confer resistance to TRAIL. Although the resistance to TRAIL-induced apoptosis is Pgp specific, TRAIL itself is not a direct substrate of Pgp. Pgp expression has no effect on the level of the TRAIL receptors DR4 and DR5. These findings might have clinical implications since the combination of TRAIL therapy with administration of Pgp modulators might sensitize TRAIL resistant tumors. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Galski, Hanan; Oved-Gelber, Tamar; Simanovsky, Masha; Nagler, Arnon] Chaim Sheba Med Ctr, Div Hematol, Lab Mol Immunol, IL-52621 Tel Hashomer, Ramat Gan, Israel.
[Lazarovici, Philip] Hebrew Univ Jerusalem, Sch Pharm, Inst Drug Sci, IL-91905 Jerusalem, Israel.
[Gottesman, Michael M.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Galski, H (reprint author), Chaim Sheba Med Ctr, Lab Mol Immunobiol, IL-52621 Tel Hashomer, Ramat Gan, Israel.
EM hgalski@sheba.health.gov.il
FU Israel Science Foundation [ISF494/04-08]; Israel Cancer Association
(ICA) [20052008]
FX This study has been performed as part of T. O-G Ph.D. thesis. This study
supported in part by grants from The Israel Science Foundation
(ISF494/04-08) and Israel Cancer Association (ICA # 20052008) granted to
H.G & A.N.
NR 36
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U1 2
U2 20
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0006-2952
J9 BIOCHEM PHARMACOL
JI Biochem. Pharmacol.
PD SEP 1
PY 2013
VL 86
IS 5
BP 584
EP 596
DI 10.1016/j.bcp.2013.06.004
PG 13
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 204XL
UT WOS:000323404500003
PM 23774624
ER
PT J
AU Dartois, V
Barry, CE
AF Dartois, Veronique
Barry, Clifton E., III
TI A medicinal chemists' guide to the unique difficulties of lead
optimization for tuberculosis
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Tuberculosis; Drug discovery
ID INTENSIVE PHASE TREATMENT; IN-VITRO MODEL; MYCOBACTERIUM-TUBERCULOSIS;
PULMONARY TUBERCULOSIS; LATENT TUBERCULOSIS; GUINEA-PIG; RABBIT MODEL;
NONREPLICATING PERSISTENCE; TREATMENT STRATEGIES; MURINE TUBERCULOSIS
AB Tuberculosis is a bacterial disease that predominantly affects the lungs and results in extensive tissue pathology. This pathology contributes to the complexity of drug development as it presents discrete microenvironments within which the bacterium resides, often under conditions where replication is limited and intrinsic drug susceptibility is low. This consolidated pathology also results in impaired vascularization that limits access of potential lead molecules to the site of infection. Translating these considerations into a target-product profile to guide lead optimization programs involves implementing unique in vitro and in vivo assays to maximize the likelihood of developing clinically meaningful candidates. (C) 2013 Published by Elsevier Ltd.
C1 [Dartois, Veronique] Univ Med & Dent New Jersey, New Jersey Med Sch, Publ Hlth Res Inst, Newark, NJ 07103 USA.
[Barry, Clifton E., III] NIAID, TB Res Sect, NIH, Bethesda, MD 20892 USA.
RP Barry, CE (reprint author), NIAID, TB Res Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM cbarry@niaid.nih.gov
RI Barry, III, Clifton/H-3839-2012
FU NIAID, NIH; Bill and Melinda Gates Foundation
FX This work was funded (in part) by the Intramural Research Program of the
NIAID, NIH (CEB) and by the TB Drug Accelerator program of the Bill and
Melinda Gates Foundation (VD).
NR 108
TC 46
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U1 2
U2 19
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD SEP 1
PY 2013
VL 23
IS 17
BP 4741
EP 4750
DI 10.1016/j.bmcl.2013.07.006
PG 10
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 202AX
UT WOS:000323187000001
PM 23910985
ER
PT J
AU Li, XP
Qi, J
Yamaguchi, T
Wang, HL
Morales, M
AF Li, Xueping
Qi, Jia
Yamaguchi, Tsuyoshi
Wang, Hui-Ling
Morales, Marisela
TI Heterogeneous composition of dopamine neurons of the rat A10 region:
molecular evidence for diverse signaling properties
SO BRAIN STRUCTURE & FUNCTION
LA English
DT Article
DE Ventral tegmental area; Substantia nigra; Reward; Corelease of dopamine
and glutamate; VGluT2
ID VENTRAL TEGMENTAL AREA; PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS;
INTERFASCICULAR NUCLEUS; GLUTAMATERGIC NEURONS; SUBSTANTIA-NIGRA;
BINDING-PROTEIN; MESSENGER-RNAS; IN-VITRO; MIDBRAIN
AB The A10 region contains different neurons: dopamine (expressing tyrosine hydroxylase; TH), GABA, glutamate-only (expressing the vesicular glutamate transporter 2; VGluT2), and TH-VGluT2 (coexpressing TH and VGluT2). We used three methods to investigate proteins necessary for the synthesis (aromatic l-amino acid decarboxylase, AADC) or transport (vesicular monoamine transporter; VMAT2 or dopamine transporter; DAT) of dopamine within TH neurons in the A10 region. By in situ hybridization-immunohistochemistry, we found that all TH neurons in the A10 region had AADC, but not all had VMAT2, DAT or D2 receptors (D2R). To determine whether TH-VGluT2 neurons account for TH neurons lacking these dopamine markers, we implemented an anatomical "mirror technique", and found that not all TH-VGluT2 neurons lacked VMAT2, DAT or D2R. Next, by quantitative RT-PCR of individual micro-dissected TH neurons, we discovered two classes of TH-VGluT2 and three classes of TH-only neurons with different latero-medial distribution. Some of the TH-VGluT2 neurons had both VMAT2 and DAT (TH-VGluT2 Class 1); others lacked detectable levels of both transporters (TH-VGluT2 Class 2). Most of the TH-only neurons contained VMAT2 and DAT (TH-only Class 1), a few had DAT without detectable VMAT2 (TH-only Class 2), and others lacked detectable levels of both transporters (TH-only Class 3). We concluded that (a) the majority of TH neurons lacking DAT are TH-VGluT2 neurons, (b) very few TH-only neurons express DAT without VMAT2, and (c) TH-VGluT2 neurons lacking DAT also lack VMAT2. Thus, the A10 region contains dopamine neurons with differential compartmentalization and unique signaling properties.
C1 [Li, Xueping; Qi, Jia; Yamaguchi, Tsuyoshi; Wang, Hui-Ling; Morales, Marisela] NIDA, Intramural Res Program, Neuronal Networks Sect, Baltimore, MD 21224 USA.
[Li, Xueping] Xian Med Univ, Xian, Peoples R China.
RP Morales, M (reprint author), NIDA, Intramural Res Program, Neuronal Networks Sect, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM mmorales@intra.nida.nih.gov
RI QI, JIA/A-6337-2014
FU National Institute on Drug Abuse
FX This work was supported by the Intramural Research Program of the
National Institute on Drug Abuse. We thank Bing Liu for her help in
processing brain tissue.
NR 43
TC 43
Z9 43
U1 1
U2 13
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1863-2653
J9 BRAIN STRUCT FUNCT
JI Brain Struct. Funct.
PD SEP
PY 2013
VL 218
IS 5
BP 1159
EP 1176
DI 10.1007/s00429-012-0452-z
PG 18
WC Anatomy & Morphology; Neurosciences
SC Anatomy & Morphology; Neurosciences & Neurology
GA 206CT
UT WOS:000323495100006
PM 22926514
ER
PT J
AU Faranesh, AZ
Lederman, RJ
AF Faranesh, Anthony Z.
Lederman, Robert J.
TI Roadmaps show the way: Coregistration to enhance structural heart
interventions
SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS
LA English
DT Editorial Material
ID MAGNETIC-RESONANCE
C1 [Faranesh, Anthony Z.; Lederman, Robert J.] NHLBI, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
RP Lederman, RJ (reprint author), NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bldg 10,Room 2C713 MSC1538, Bethesda, MD 20892 USA.
EM lederman@nih.gov
OI lederman, robert/0000-0003-1202-6673
FU Intramural NIH HHS [ZID HL006061-04, ZIA HL006039-04]; NHLBI NIH HHS
[ZIA HL005062]
NR 5
TC 1
Z9 1
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1522-1946
J9 CATHETER CARDIO INTE
JI Catheter. Cardiovasc. Interv.
PD SEP 1
PY 2013
VL 82
IS 3
BP 443
EP 444
DI 10.1002/ccd.25115
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 205OP
UT WOS:000323454100043
PM 24038978
ER
PT J
AU Palys, KE
Berger, VW
Alperson, S
AF Palys, Kaitlin E.
Berger, Vance W.
Alperson, Sunny
TI Trial quality checklists: on the need to multiply (not add) scores
SO CLINICAL ORAL INVESTIGATIONS
LA English
DT Letter
C1 [Palys, Kaitlin E.] Virginia Polytech Inst & State Univ, Blacksburg, VA 24061 USA.
[Berger, Vance W.] NCI, Biometry Res Grp, Bethesda, MD 20892 USA.
[Berger, Vance W.] UMBC, Bethesda, MD 20892 USA.
[Alperson, Sunny] Montgomery Coll, Takoma Pk, MD USA.
RP Palys, KE (reprint author), Virginia Polytech Inst & State Univ, Blacksburg, VA 24061 USA.
EM palysk@vt.edu; vb78c@nih.gov; sunny.alperson@montgomerycollege.edu
NR 5
TC 1
Z9 1
U1 0
U2 3
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1432-6981
J9 CLIN ORAL INVEST
JI Clin. Oral Investig.
PD SEP
PY 2013
VL 17
IS 7
BP 1789
EP 1790
DI 10.1007/s00784-013-1020-5
PG 2
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 203EP
UT WOS:000323274000020
PM 23793406
ER
PT J
AU Mercado-Feliciano, M
Herbert, RA
Wyde, ME
Gerken, DK
Hejtmancik, MR
Hooth, MJ
AF Mercado-Feliciano, Minerva
Herbert, Ronald A.
Wyde, Michael E.
Gerken, Diane K.
Hejtmancik, Milton R.
Hooth, Michelle J.
TI Pyrogallol-associated dermal toxicity and carcinogenicity in F344/N rats
and B6C3F1/N mice
SO CUTANEOUS AND OCULAR TOXICOLOGY
LA English
DT Article
DE Hyperkeratosis; hyperplasia; pyrogallol; squamous cell carcinoma;
squamous papilloma
ID ZERO DOSE CONTROL; CONTACT-DERMATITIS; HAIR-DYES; HAIRDRESSERS;
MUTAGENICITY; POLYPHENOLS; AGENTS
AB Pyrogallol (CAS No. 87-66-1), a benzenetriol used historically as a hair dye and currently in a number of industrial applications, was nominated to the National Toxicology Program (NTP) for testing based on the lack of toxicity and carcinogenicity data. Three-month and two-year toxicity studies to determine the toxicity and carcinogenicity of pyrogallol when applied to naive skin (i.e. dermal administration) were conducted in both sexes of F344/N rats and B6C3F1/N mice. In the three-month studies, adult rodents were administered pyrogallol in 95% ethanol five days per week for 3 months at doses of up to 150 mg/kg body weight (rats) or 600 mg/kg (mice). Based on the subchronic studies, the doses for the two-year studies in rats and mice were 5, 20 and 75 mg/kg of pyrogallol. All mice and most rats survived until the end of the three-month study and body weights were comparable to controls. During the two-year study, survival of dosed rats and male mice was comparable to controls; however survival of 75 mg/kg female mice significantly decreased compared to controls. The incidences of microscopic non-neoplastic lesions at the site of application were significantly higher in all dosed groups of rats and mice and in both the 3-months and two-year studies. In the two-year study, hyperplasia, hyperkeratosis and inflammation tended to be more severe in mice than in rats, and in the mice they tended to be more severe in females than in males. The incidence of squamous cell carcinoma at the site of application (SOA) in 75 mg/kg female mice and SOA squamous cell papillomas in 75 mg/kg male mice were greater than controls. Pyrogallol was carcinogenic in female mice and may have caused tumors in male mice.
C1 [Mercado-Feliciano, Minerva; Herbert, Ronald A.; Wyde, Michael E.; Hooth, Michelle J.] NIEHS, Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA.
[Gerken, Diane K.; Hejtmancik, Milton R.] Battelle Mem Inst, Columbus, OH 43201 USA.
RP Hooth, MJ (reprint author), NIEHS, 111 Alexander Dr,Mail Drop K2-13, Res Triangle Pk, NC 27709 USA.
EM hooth@niehs.nih.gov
FU Intramural NIH HHS [Z99 ES999999]
NR 32
TC 2
Z9 2
U1 3
U2 11
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1556-9527
EI 1556-9535
J9 CUTAN OCUL TOXICOL
JI Cutan. Ocul. Toxicol.
PD SEP
PY 2013
VL 32
IS 3
BP 234
EP 240
DI 10.3109/15569527.2012.746358
PG 7
WC Ophthalmology; Toxicology
SC Ophthalmology; Toxicology
GA 206BH
UT WOS:000323490400008
PM 23231012
ER
PT J
AU Laronda, MM
Unno, K
Ishi, K
Serna, VA
Butler, LM
Mills, AA
Orvis, GD
Behringer, RR
Deng, CX
Sinha, S
Kurita, T
AF Laronda, Monica M.
Unno, Kenji
Ishi, Kazutomo
Serna, Vanida A.
Butler, Lindsey M.
Mills, Alea A.
Orvis, Grant D.
Behringer, Richard R.
Deng, Chuxia
Sinha, Satrajit
Kurita, Takeshi
TI Diethylstilbestrol induces vaginal adenosis by disrupting
SMAD/RUNX1-mediated cell fate decision in the Mallerian duct epithelium
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE DES daughter; Vaginal clear cell adenocarcinoma; Endocrine disruptor;
p63
ID ESTROGEN-RECEPTOR-ALPHA; KNOCKOUT MICE; P53 HOMOLOG; IN-UTERO; P63;
FEMALE; EXPOSURE; MOUSE; DIFFERENTIATION; PROLIFERATION
AB Women exposed to diethylstilbestrol (DES) in utero frequently develop vaginal adenosis, from which clear cell adenocarcinoma can arise. Despite decades of extensive investigation, the molecular pathogenesis of DES-associated vaginal adenosis remains elusive. Here we report that DES induces vaginal adenosis by inhibiting the BMP4/Activin A-regulated vaginal cell fate decision through a downregulation of RUNX1. BMP4 and Activin A produced by vaginal mesenchyme synergistically activated the expression of Delta Np63, thus deciding vaginal epithelial cell fate in the Mullerian duct epithelial cells (MDECs) via direct binding of SMADs on the highly conserved 5' sequence of Delta Np63. Therefore, mice in which Smad4 was deleted in MDECs failed to express Delta Np63 in vaginal epithelium and developed adenosis. This SMAD-dependent Delta Np63 activation required RUNX1, a binding partner of SMADs. Conditional deletion of Runx1 in the MDECs induced adenosis in the cranial portion of vagina, which mimicked the effect of developmental DES-exposure. Furthermore, neonatal DES exposure downregulated RUNX1 in the fornix of the vagina, where DES-associated adenosis is frequently found. This observation strongly suggests that the downregulation of RUNX1 is the cause of vaginal adenosis. However, once cell fate was determined, the BMP/Activin-SMAD/RUNX1 signaling pathway became dispensable for the maintenance of Delta Np63 expression in vaginal epithelium. Instead, the activity of the Delta Np63 locus in vaginal epithelium was maintained by a Delta Np63-dependent mechanism. This is the first demonstration of a molecular mechanism through which developmental chemical exposure causes precancerous lesions by altering cell fate. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Laronda, Monica M.; Unno, Kenji; Ishi, Kazutomo; Serna, Vanida A.; Butler, Lindsey M.; Kurita, Takeshi] Northwestern Univ, Feinberg Sch Med, Dept Obstet & Gynecol, Div Reprod Biol, Chicago, IL 60611 USA.
[Mills, Alea A.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
[Orvis, Grant D.; Behringer, Richard R.] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA.
[Deng, Chuxia] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20817 USA.
[Sinha, Satrajit] SUNY Buffalo, Dept Biochem, Ctr Excellence Bioinformat & Life Sci, Buffalo, NY 14203 USA.
RP Kurita, T (reprint author), 303 E Super St,Lurie 7-117, Chicago, IL 60611 USA.
EM t-kurita@northwestern.edu
RI Laronda, Monica/F-9136-2014; Kurita, Takeshi/A-2236-2013; deng,
chuxia/N-6713-2016
OI Kurita, Takeshi/0000-0003-4281-5884;
FU National Institutes of Health [HD30284, RO1CA154358, RO1HD064402]
FX The authors thank Dr. So-Youn Kim for technical help and Stacy A.
Druschitz, Drs. So-Youn Kim, Tsutomu Kume and Gerald R. Cunha for
editorial suggestions. This work was supported by the National
Institutes of Health [HD30284 to R.R.B, RO1CA154358 and RO1HD064402 to
T.K.].
NR 48
TC 7
Z9 7
U1 1
U2 13
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 SEP 1
PY 2013
VL 381
IS 1
BP 5
EP 16
DI 10.1016/j.ydbio.2013.06.024
PG 12
WC Developmental Biology
SC Developmental Biology
GA 204WL
UT WOS:000323401900003
PM 23830984
ER
PT J
AU Rothschild, SC
Lahvic, J
Francescatto, L
McLeod, JJA
Burgess, SM
Tombes, RM
AF Rothschild, Sarah C.
Lahvic, Jamie
Francescatto, Ludmila
McLeod, Jamie J. A.
Burgess, Shawn M.
Tombes, Robert M.
TI CaMK-II activation is essential for zebrafish inner ear development and
acts through Delta-Notch signaling
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE CaMK-II; Cilia; Otolith; Inner ear; Delta-notch
ID PROTEIN-KINASE-II; DRIVEN FLUID-FLOW; MIND-BOMB MUTANT; HAIR-CELLS;
OTOLITH FORMATION; CILIARY MOTILITY; SYNAPTIC VESICLES;
EPITHELIAL-CELLS; KUPFFERS VESICLE; OTIC VESICLE
AB Zebrafish inner ear development is characterized by the crystallization of otoliths onto immotile kinocilia that protrude from sensory "hair" cells. The stereotypical formation of these sensory structures is dependent on the expression of key patterning genes and on Ca2+ signals. One potential target of Ca2+ signaling in the inner ear is the type II Ca2+/calmodulin-dependent protein kinase (CaMK-II), which is preferentially activated in hair cells, with intense activation at the base of kinocilia. In zebrafish, CaMK-II is encoded by seven genes; the expression of one of these genes (camk2g1) is enriched in hair cells. The suppression of camk2g1 expression by antisense morpholino oligonucleotides or inhibition of CaMK-II activation by the pharmacological antagonist, KN-93, results in aberrant otolith formation without preventing cilia formation. In fact, CaMK-II suppression results in additional ciliated hair cells and altered levels of Delta Notch signaling members. DeltaA and deltaD transcripts are increased and DeltaD protein accumulates in hair cells of CaMK-II morphants, indicative of defective recycling and/or exocytosis. Our findings indicate that CaMK-II plays a critical role in the developing ear, influencing cell differentiation through extranuclear effects on Delta Notch signaling. Continued expression and activation of CaMK-II in maculae and cristae in older embryos suggests continued roles in auditory sensory maturation and transduction. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Rothschild, Sarah C.; Lahvic, Jamie; Francescatto, Ludmila; McLeod, Jamie J. A.; Tombes, Robert M.] Virginia Commonwealth Univ, Dept Biol, Richmond, VA 23284 USA.
[Burgess, Shawn M.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA.
RP Tombes, RM (reprint author), Virginia Commonwealth Univ, Dept Biol, Richmond, VA 23284 USA.
EM rtombes@vcu.edu
OI Burgess, Shawn/0000-0003-1147-0596
FU National Science Foundation [IOS-0817658]
FX The authors gratefully acknowledge Paul Vorster, Minh Nguyen, Bennett
Childs, Rachel Troch, and Amritha Yelamilli for their assistance with
this study and Amanda Dickinson, Greg Walsh, James Lister, Bruce Riley,
Bernard Thisse, Alan Davidson, Lila Solnica-Krezel, and lain Drummond
for sharing useful reagents and advice. Supported by National Science
Foundation Grant IOS-0817658.
NR 63
TC 2
Z9 2
U1 0
U2 10
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 SEP 1
PY 2013
VL 381
IS 1
BP 179
EP 188
DI 10.1016/j.ydbio.2013.05.028
PG 10
WC Developmental Biology
SC Developmental Biology
GA 204WL
UT WOS:000323401900018
PM 23747599
ER
PT J
AU Toyama, R
Kim, MH
Rebbert, ML
Gonzales, J
Burgess, H
Dawid, IB
AF Toyama, Reiko
Kim, Mi Ha
Rebbert, Martha L.
Gonzales, John
Burgess, Harold
Dawid, Igor B.
TI Habenular commissure formation in zebrafish is regulated by the pineal
gland-specific gene unc119c
SO DEVELOPMENTAL DYNAMICS
LA English
DT Article
DE Zebrafish; pineal gland; epiphysis; habenular commissure; unc119; wnt4
ID RETINAL DEGENERATION; WNT PROTEINS; TRANSMEMBRANE PROTEIN;
NERVOUS-SYSTEM; PHOTORECEPTOR; TRAFFICKING; SECRETION; ABLATION;
ELEGANS; NITROREDUCTASE
AB Background: The zebrafish pineal gland (epiphysis) is a site of melatonin production, contains photoreceptor cells, and functions as a circadian clock pacemaker. Since it is located on the surface of the forebrain, it is accessible for manipulation and, therefore, is a useful model system to analyze pineal gland function and development. We previously analyzed the pineal transcriptome during development and showed that many genes exhibit a highly dynamic expression pattern in the pineal gland. Results: Among genes preferentially expressed in the zebrafish pineal gland, we identified a tissue-specific form of the unc119 gene family, unc119c, which is highly preferentially expressed in the pineal gland during day and night at all stages examined from embryo to adult. When expression of unc119c was inhibited, the formation of the habenular commissure (HC) was specifically compromised. The Unc119c interacting factors Arl3l1 and Arl3l2 as well as Wnt4a also proved indispensible for HC formation. Conclusions: We suggest that Unc119c, together with Arl3l1/2, plays an important role in modulating Wnt4a production and secretion during HC formation in the forebrain of the zebrafish embryo. Developmental Dynamics 242: 10331042, 2013. (C) 2013 Wiley Periodicals, Inc.
C1 [Toyama, Reiko; Kim, Mi Ha; Rebbert, Martha L.; Burgess, Harold; Dawid, Igor B.] NICHD, Program Genom Dev, NIH, Bethesda, MD USA.
[Gonzales, John] NICHD, Charles River, NIH, Bethesda, MD USA.
RP Dawid, IB (reprint author), Bldg 6B,Room 420,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM idawid@nih.gov
RI Burgess, Harold/B-8474-2015
OI Burgess, Harold/0000-0003-1966-7801
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX Grant sponsor: Intramural Research Program of the Eunice Kennedy Shriver
National Institute of Child Health and Human Development.
NR 46
TC 4
Z9 5
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1058-8388
J9 DEV DYNAM
JI Dev. Dyn.
PD SEP
PY 2013
VL 242
IS 9
BP 1033
EP 1042
DI 10.1002/dvdy.23994
PG 10
WC Anatomy & Morphology; Developmental Biology
SC Anatomy & Morphology; Developmental Biology
GA 203TB
UT WOS:000323315200004
PM 23749482
ER
PT J
AU Hsu, JC
Koo, H
Harunaga, JS
Matsumoto, K
Doyle, AD
Yamada, KM
AF Hsu, Jeff C.
Koo, Hyun
Harunaga, Jill S.
Matsumoto, Kazue
Doyle, Andrew D.
Yamada, Kenneth M.
TI Region-specific epithelial cell dynamics during branching morphogenesis
SO DEVELOPMENTAL DYNAMICS
LA English
DT Article
DE organ morphogenesis; salivary gland; cell migration; basement membrane;
integrin; myosin II; E-cadherin; KikGR
ID MOUSE SUBMANDIBULAR-GLAND; EXTRACELLULAR-MATRIX; LUNG DEVELOPMENT;
MYOSIN-IIA; MIGRATION; PHOSPHORYLATION; MECHANISMS; MORPHOLOGY;
INVASION; INSIGHTS
AB Background: Epithelial cells of developing embryonic organs, such as salivary glands, can display substantial motility during branching morphogenesis. Their dynamic movements and molecules involved in their migration are not fully characterized. Results: We generated transgenic mice expressing photoconvertible KikGR and tracked the movements of individual cells highlighted by red fluorescence in different regions of developing salivary glands. Motility was highest for outer bud epithelial cells adjacent to the basement membrane, lower in inner bud cells, and lowest in duct cells. The highly motile outer cells contacting the basement membrane were pleomorphic, whereas inner cells were rounded. Peripheral cell motility was disrupted by antibodies inhibiting alpha 6+beta 1 integrins and the nonmuscle myosin II inhibitor blebbistatin. Inner bud cell migration was unaffected by these inhibitors, but their rate of migration was stimulated by inhibiting E-cadherin. Conclusions: Cell motility in developing salivary glands was highest in cells in contact with the basement membrane. The basement membrane-associated motility of these outer bud cells depended on integrins and myosin II, but not E-cadherin. In contrast, motility of inner bud cells was restrained by E-cadherin. These findings identify the importance of integrin-dependent basement membrane association for the morphology, tissue organization, and lateral motility of morphogenetic epithelial cells. Developmental Dynamics 242: 1066-1077, 2013. (C) 2013 Wiley Periodicals, Inc.
C1 [Hsu, Jeff C.; Koo, Hyun; Harunaga, Jill S.; Matsumoto, Kazue; Doyle, Andrew D.; Yamada, Kenneth M.] NIDCR, Cell Biol Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
[Koo, Hyun] Univ Rochester, Med Ctr, Ctr Oral Biol, Rochester, NY 14642 USA.
RP Doyle, AD (reprint author), NIDCR, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
EM kenneth.yamada@nih.gov
FU National Institute of Dental and Craniofacial Research, National
Institutes of Health
FX We thank Dr. Atsushi Miyawaki for the KikGR photo-convertible
fluorescence probe and for advice, Dr. Kenn Holmbeck for advice on
recombineering, Dr. Andrzej Dlugosz for the pCLE GFP plasmid, and Andrew
Cho, Bradford Hall, Ashok Kulkarni, and the NIDCR Gene Targeting Core
for generating KikGR transgenic mouse lines. Supported by the Intramural
Research Program of the National Institute of Dental and Craniofacial
Research, National Institutes of Health.
NR 49
TC 16
Z9 16
U1 1
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1058-8388
J9 DEV DYNAM
JI Dev. Dyn.
PD SEP
PY 2013
VL 242
IS 9
BP 1066
EP 1077
DI 10.1002/dvdy.24000
PG 12
WC Anatomy & Morphology; Developmental Biology
SC Anatomy & Morphology; Developmental Biology
GA 203TB
UT WOS:000323315200007
PM 23780688
ER
PT J
AU Lizunov, VA
Lee, JP
Skarulis, MC
Zimmerberg, J
Cushman, SW
Stenkula, KG
AF Lizunov, Vladimir A.
Lee, Jo-Ping
Skarulis, Monica C.
Zimmerberg, Joshua
Cushman, Samuel W.
Stenkula, Karin G.
TI Impaired Tethering and Fusion of GLUT4 Vesicles in Insulin-Resistant
Human Adipose Cells
SO DIABETES
LA English
DT Article
ID FAT-CELLS; DIABETES-MELLITUS; PLASMA-MEMBRANE; PHOSPHORYLATION;
TRANSLOCATION; ADIPOCYTES; OBESITY; SURFACE; TRAFFICKING; DISEASE
AB Systemic glucose homeostasis is profoundly influenced by adipose cell function. Here we investigated GLUT4 dynamics in living adipose cells from human subjects with varying BMI and insulin sensitivity index (S-i) values. Cells were transfected with hemagglutinin (HA)-GLUT4-green fluorescent protein (GFP)/mCherry (red fluorescence), and were imaged live using total internal reflection fluorescence and confocal microscopy. HA-GLUT4-GFP redistribution to the plasma membrane (PM) was quantified by surface-exposed HA epitope. In the basal state, GLUT4 storage vesicle (GSV) trafficking to and fusion with the PM were invariant with donor subject S-i, as was total cell-surface GLUT4. In cells from insulin-sensitive subjects, insulin augmented GSV tethering and fusion approximately threefold, resulting in a corresponding increase in total PM GLUT4. However, with decreasing S-i, these effects diminished progressively. All insulin-induced effects on GLUT4 redistribution and trafficking correlated strongly with S-i and only weakly with BMI. Thus, while basal GLUT4 dynamics and total cell-surface GLUT4 are intact in human adipose cells, independent of donor S-i, cells from insulin-resistant donors show markedly impaired GSV tethering and fusion responses to insulin, even after overnight culture. This altered insulin responsiveness is consistent with the hypothesis that adipose cellular dysfunction is a primary contributor to systemic metabolic dysfunction.
C1 [Lizunov, Vladimir A.; Zimmerberg, Joshua] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD USA.
[Lee, Jo-Ping; Cushman, Samuel W.; Stenkula, Karin G.] NIH, Expt Diabet Metab & Nutr Sect, Bethesda, MD 20892 USA.
[Skarulis, Monica C.] Natl Inst Diabet & Digest & Kidney Dis, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD USA.
[Stenkula, Karin G.] Lund Univ, Lund, Sweden.
RP Zimmerberg, J (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD USA.
EM joshz@mail.nih.gov
RI Bai, Li/N-8311-2013
FU Intramural Research Programs of the National Institute of Diabetes and
Digestive and Kidney Diseases; Eunice Kennedy Shriver National Institute
of Child Health and Human Development, National Institutes of Health
FX This work was supported by the Intramural Research Programs of the
National Institute of Diabetes and Digestive and Kidney Diseases and the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health.
NR 25
TC 7
Z9 7
U1 0
U2 7
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD SEP
PY 2013
VL 62
IS 9
BP 3114
EP 3119
DI 10.2337/db12-1741
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 205DG
UT WOS:000323421000018
PM 23801575
ER
PT J
AU Deshpande, SD
Putta, S
Wang, M
Lai, JY
Bitzer, M
Nelson, RG
Lanting, LL
Kato, M
Natarajan, R
AF Deshpande, Supriya D.
Putta, Sumanth
Wang, Mei
Lai, Jennifer Y.
Bitzer, Markus
Nelson, Robert G.
Lanting, Linda L.
Kato, Mitsuo
Natarajan, Rama
TI Transforming Growth Factor-beta-Induced Cross Talk Between p53 and a
MicroRNA in the Pathogenesis of Diabetic Nephropathy
SO DIABETES
LA English
DT Article
ID KIDNEY-DISEASE; RENAL FIBROSIS; EXPRESSION; MECHANISM; PATHWAY; INJURY;
GENE; CONTRIBUTES; ACTIVATION; GLOMERULI
AB Elevated p53 expression is associated with several kidney diseases including diabetic nephropathy (DN). However, the mechanisms are unclear. We report that expression levels of transforming growth factor-beta 1 (TGF-beta), p53, and microRNA-192 (miR-192) are increased in the renal cortex of diabetic mice, and this is associated with enhanced glomerular expansion and fibrosis relative to nondiabetic mice. Targeting miR-192 with locked nucleic acid-modified inhibitors in vivo decreases expression of p53 in the renal cortex of control and streptozotocin-injected diabetic mice. Furthermore, mice with genetic deletion of miR-192 in vivo display attenuated renal cortical TGF-beta and p53 expression when made diabetic, and have reduced renal fibrosis, hypertrophy, proteinuria, and albuminuria relative to diabetic wild-type mice. In vitro promoter regulation studies show that TGF-beta induces reciprocal activation of miR-192 and p53, via the miR-192 target Zeb2, leading to augmentation of downstream events related to DN. Inverse correlation between miR-192 and Zeb2 was observed in glomeruli of human subjects with early DN, consistent with the mechanism seen in mice. Our results demonstrate for the first time a TGF-beta-induced feedback amplification circuit between p53 and miR-192 related to the pathogenesis of DN, and that miR-192-knockout mice are protected from key features of DN.
C1 [Deshpande, Supriya D.; Natarajan, Rama] City Hope Natl Med Ctr, Beckman Res Inst, Irell & Manella Grad Sch Biol Sci, Duarte, CA USA.
[Deshpande, Supriya D.; Putta, Sumanth; Wang, Mei; Lanting, Linda L.; Kato, Mitsuo; Natarajan, Rama] City Hope Natl Med Ctr, Beckman Res Inst, Dept Diabet & Metab Dis Res, Div Mol Diabet Res, Duarte, CA USA.
[Lai, Jennifer Y.; Bitzer, Markus] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Nelson, Robert G.] Natl Inst Diabet & Digest & Kidney Dis, NIH, Phoenix, AZ USA.
RP Natarajan, R (reprint author), City Hope Natl Med Ctr, Beckman Res Inst, Irell & Manella Grad Sch Biol Sci, Duarte, CA USA.
EM mkato@coh.org; rnatarajan@coh.org
RI Kato, Mitsuo/D-5411-2009
FU National Institutes of Health [R01-DK-081705, R01-DK-058191]; Intramural
Research Program of the National Institute of Diabetes and Digestive and
Kidney Diseases
FX This work was supported by grants from the National Institutes of Health
(R01-DK-081705 and R01-DK-058191 to R.N.) and by the Intramural Research
Program of the National Institute of Diabetes and Digestive and Kidney
Diseases (to R.G.N.).
NR 49
TC 53
Z9 58
U1 1
U2 27
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD SEP
PY 2013
VL 62
IS 9
BP 3151
EP 3162
DI 10.2337/db13-0305
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 205DG
UT WOS:000323421000022
PM 23649518
ER
PT J
AU Weil, EJ
Fufaa, G
Jones, LI
Lovato, T
Lemley, KV
Hanson, RL
Knowler, WC
Bennett, PH
Yee, B
Myers, BD
Nelson, RG
AF Weil, E. Jennifer
Fufaa, Gudeta
Jones, Lois I.
Lovato, Tracy
Lemley, Kevin V.
Hanson, Robert L.
Knowler, William C.
Bennett, Peter H.
Yee, Berne
Myers, Bryan D.
Nelson, Robert G.
TI Effect of Losartan on Prevention and Progression of Early Diabetic
Nephropathy in American Indians With Type 2 Diabetes
SO DIABETES
LA English
DT Article
ID GLOMERULAR STRUCTURAL-CHANGES; CONVERTING-ENZYME-INHIBITOR; MELLITUS;
MICROALBUMINURIA; DISEASE; IRBESARTAN; ENALAPRIL; YOUNG
AB Angiotensin receptor blockers are renoprotective in hypertensive azotemic patients with type 2 diabetes, but their efficacy in early diabetic kidney disease is uncertain. We performed a 6-year randomized clinical trial in 169 American Indians with type 2 diabetes and normoalbuminuria (albumin/creatinine ratio [ACR] <30 mg/g; n = 91) or microalbuminuria (ACR 30-299 mg/g; n = 78) at baseline. The primary outcome was decline in glomerular filtration rate (GFR) to 60 mL/min or to half the baseline value in subjects who entered with GFR <120 mL/min. Another outcome was differences in glomerular structure at end of treatment. Subjects received 100 mg losartan or placebo daily. GFR was measured annually; 111 subjects underwent kidney biopsies. Only nine subjects reached the GFR outcome, and the unadjusted hazard ratio (losartan vs. placebo) was 0.50 (95% CI, 0.12-1.99). Differences in mesangial fractional volume were not estimated in the combined albuminuria groups because of an interaction with treatment assignment. In separate analyses, mesangial fractional volume was lower in subjects treated with losartan in the microalbuminuria group (18.8 vs. 25.6%; P = 0.02), but not in the normoalbuminuria group (19.6 vs. 17.8%; P = 0.86). Treatment with losartan may preserve some features of kidney structure in American Indians with type 2 diabetes and microalbuminuria.
C1 [Weil, E. Jennifer; Fufaa, Gudeta; Jones, Lois I.; Lovato, Tracy; Hanson, Robert L.; Knowler, William C.; Bennett, Peter H.; Nelson, Robert G.] Natl Inst Diabet & Digest & Kidney Dis, NIH, Phoenix, AZ USA.
[Lemley, Kevin V.] Childrens Hosp Los Angeles, Div Nephrol, Los Angeles, CA 90027 USA.
[Yee, Berne] Southwest Kidney Inst, Phoenix, AZ USA.
[Myers, Bryan D.] Stanford Univ, Div Nephrol, Sch Med, Stanford, CA 94305 USA.
RP Nelson, RG (reprint author), Natl Inst Diabet & Digest & Kidney Dis, NIH, Phoenix, AZ USA.
EM rnelson@nih.gov
RI Hanson, Robert/O-3238-2015
OI Hanson, Robert/0000-0002-4252-7068
FU National Institute of Diabetes and Digestive and Kidney Diseases;
American Diabetes Association [1-08-CR-42]
FX This research was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases, the
American Diabetes Association (Clinical Science Award 1-08-CR-42), and
by Merck, which provided the study drug and placebo tablets. No other
potential conflicts of interest relevant to this article were reported.
NR 26
TC 24
Z9 24
U1 1
U2 7
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD SEP
PY 2013
VL 62
IS 9
BP 3224
EP 3231
DI 10.2337/db12-1512
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 205DG
UT WOS:000323421000030
PM 23545707
ER
PT J
AU Bonner, JS
Lantier, L
Hocking, KM
Kang, L
Owolabi, M
James, FD
Bracy, DP
Brophy, CM
Wasserman, DH
AF Bonner, Jeffrey S.
Lantier, Louise
Hocking, Kyle M.
Kang, Li
Owolabi, Mark
James, Freyja D.
Bracy, Deanna P.
Brophy, Colleen M.
Wasserman, David H.
TI Relaxin Treatment Reverses Insulin Resistance in Mice Fed a High-Fat
Diet
SO DIABETES
LA English
DT Article
ID MUSCLE GLUCOSE-UPTAKE; ENDOTHELIAL GROWTH-FACTOR; SKELETAL-MUSCLE;
IN-VIVO; BLOOD-FLOW; POTENTIAL MECHANISM; HYPERTENSIVE-RATS; CAPILLARY
DENSITY; NITRIC-OXIDE; MICROVASCULAR RECRUITMENT
AB The endogenous hormone relaxin increases vascular reactivity and angiogenesis. We demonstrate that acute relaxin infusion in lean C57BL/6J mice enhances skeletal muscle perfusion and augments muscle glucose uptake during a hyperinsulinemic-euglycemic clamp. However, an acute effect was absent in mice fed a high-fat (HF) diet for 13 weeks. In contrast, mice fed an HF diet for 13 weeks and continuously treated with relaxin for the final 3 weeks of the diet exhibited decreased fasting blood glucose. Insulin-stimulated whole-body glucose disappearance and percent suppression of hepatic glucose production are corrected by chronic relaxin. The increase in peripheral glucose utilization is a result of augmented in vivo skeletal muscle glucose uptake. Relaxin intervention improves endothelial-dependent vascular reactivity and induces a two-fold proliferation in skeletal muscle capillarity. The metabolic effects of the treatment are not attributed to changes in myocellular insulin signaling. Relaxin intervention reverses the accumulation of collagen III in the liver and collagen III and collagen IV in the heart; this is induced by HF feeding. These studies show the potential of relaxin in the treatment of diet-induced insulin resistance and vascular dysfunction. Relaxin provides a novel therapeutic approach targeting the extramyocellular barriers to insulin action, which are critical to the pathogenesis of insulin resistance.
C1 [Bonner, Jeffrey S.; Lantier, Louise; Kang, Li; Owolabi, Mark; James, Freyja D.; Bracy, Deanna P.; Wasserman, David H.] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37212 USA.
[Kang, Li; Bracy, Deanna P.; Wasserman, David H.] Vanderbilt Univ, Sch Med, Mouse Metab Phenotyping Ctr, Nashville, TN 37212 USA.
[Hocking, Kyle M.; Brophy, Colleen M.] Vanderbilt Univ, Sch Med, Dept Surg, Div Vasc Surg, Nashville, TN 37212 USA.
RP Bonner, JS (reprint author), Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37212 USA.
EM jeffrey.s.bonner@vanderbilt.edu
FU National Institutes of Health [DK054902, DK059637]; Diabetes Research
and Training Center [DK20593]
FX This work was funded by National Institutes of Health grants DK054902
andDK059637 (Mouse Metabolic Phenotyping Center). The Diabetes Research
and Training Center (DK20593) also provided support for this work.
NR 62
TC 15
Z9 15
U1 0
U2 5
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD SEP
PY 2013
VL 62
IS 9
BP 3251
EP 3260
DI 10.2337/db13-0033
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 205DG
UT WOS:000323421000033
PM 23801576
ER
PT J
AU Horton, JK
Stefanick, DF
Gassman, NR
Williams, JG
Gabel, SA
Cuneo, MJ
Prasad, R
Kedar, PS
DeRose, EF
Hou, EW
London, RE
Wilson, SH
AF Horton, Julie K.
Stefanick, Donna F.
Gassman, Natalie R.
Williams, Jason G.
Gabel, Scott A.
Cuneo, Matthew J.
Prasad, Rajendra
Kedar, Padmini S.
DeRose, Eugene F.
Hou, Esther W.
London, Robert E.
Wilson, Samuel H.
TI Preventing oxidation of cellular XRCC1 affects PARP-mediated DNA damage
responses
SO DNA REPAIR
LA English
DT Article
DE DNA polymerase beta; XRCC1; PARP-1; Methyl methanesulfonate; PARP
inhibitor; Poly(ADP-ribose)
ID STRAND-BREAK REPAIR; BASE EXCISION-REPAIR; POLYMERASE-BETA INTERACTION;
LIGASE III-ALPHA; BRCT DOMAIN; NUCLEAR ANTIGEN; PROTEIN; CELLS;
POLY(ADP-RIBOSE); HYPERSENSITIVITY
AB Poly(ADP-ribose) polymerase-1 (PARP-1) binds intermediates of base excision repair (BER) and becomes activated for poly(ADP-ribose) (PAR) synthesis. PAR mediates recruitment and functions of the key BER factors XRCC1 and DNA polymerase beta (pol beta) that in turn regulate PAR. Yet, the molecular mechanism and implications of coordination between XRCC1 and pol beta in regulating the level of PAR are poorly understood. A complex of PARP-1, XRCC1 and pol beta is found in vivo, and it is known that pol beta and XRCC1 interact through a redox-sensitive binding interface in the N-terminal domain of XRCC1. We confirmed here that both oxidized and reduced forms of XRCC1 are present in mouse fibroblasts. To further understand the importance of the C12-C20 oxidized form of XRCC1 and the interaction with pol beta, we characterized cell lines representing stable transfectants in Xrcc1(-/-) mouse fibroblasts of wildtype XRCC1 and two mutants of XRCC1, a novel reduced form with the C12-C20 disulfide bond blocked (C12A) and a reference mutant that is unable to bind pol beta (V88R). XRCC1-deficient mouse fibroblasts are extremely hypersensitive to methyl methanesulfonate (MMS), and transfected wild-type and C12A mutant XRCC1 proteins similarly reversed MMS hypersensitivity. However, after MMS exposure the cellular PAR level was found to increase to a much greater extent in cells expressing the C12A mutant than in cells expressing wild-type XRCC1. PARP inhibition resulted in very strong MMS sensitization in cells expressing wild-type XRCC1, but this sensitization was much less in cells expressing the C12A mutant. The results suggest a role for the oxidized form of XRCC1 in the interaction with pol beta in (1) controlling the PAR level after MMS exposure and (2) enabling the extreme cytotoxicity of PARP inhibition during the MMS DNA damage response. Published by Elsevier B.V.
C1 [Horton, Julie K.; Stefanick, Donna F.; Gassman, Natalie R.; Williams, Jason G.; Gabel, Scott A.; Prasad, Rajendra; Kedar, Padmini S.; DeRose, Eugene F.; Hou, Esther W.; London, Robert E.; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Cuneo, Matthew J.] Oak Ridge Natl Lab, Biol & Soft Matter Div, Oak Ridge, TN 37831 USA.
RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, 111 TW Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA.
EM wilson5@niehs.nih.gov
OI Gassman, Natalie/0000-0002-8488-2332; Cuneo, Matthew/0000-0002-1475-6656
FU Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences [Z01 ES050158, ES050159, Z01 ES050147]
FX This work was supported by the Intramural Research Program of the NIH,
National Institute of Environmental Health Sciences (project numbers Z01
ES050158, ES050159 to S.H.W. and Z01 ES050147 to R.E.L.).
NR 37
TC 12
Z9 14
U1 0
U2 13
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
J9 DNA REPAIR
JI DNA Repair
PD SEP
PY 2013
VL 12
IS 9
BP 774
EP 785
DI 10.1016/j.dnarep.2013.06.004
PG 12
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA 205TT
UT WOS:000323468400010
PM 23871146
ER
PT J
AU Akers, NK
Lan, Q
McHale, CM
Zhang, L
Thomas, R
Hubbard, AE
Rappaport, SM
Vermeulen, R
Lee, G
Yin, S
Rothman, N
Smith, MT
AF Akers, N. K.
Lan, Q.
McHale, C. M.
Zhang, L.
Thomas, R.
Hubbard, A. E.
Rappaport, S. M.
Vermeulen, R.
Lee, G.
Yin, S.
Rothman, N.
Smith, M. T.
TI Application of RNA Sequencing to Detect Fusion Transcripts in
Benzene-Exposed Workers.
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Meeting Abstract
CT 44th Annual Meeting of the
Environmental-Mutagenesis-and-Genomics-Society (EMGS)
CY SEP 21-25, 2013
CL Monterey, CA
SP Environm Mutagenesis & Genom Soc (EMGS)
C1 [Akers, N. K.; McHale, C. M.; Zhang, L.; Thomas, R.; Hubbard, A. E.; Rappaport, S. M.; Smith, M. T.] Univ Calif Berkeley, Sch Publ Hlth, Superfund Res Program, Berkeley, CA 94720 USA.
[Lan, Q.; Rothman, N.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Vermeulen, R.] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands.
[Lee, G.; Yin, S.] Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China.
NR 0
TC 0
Z9 0
U1 0
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD SEP
PY 2013
VL 54
SU 1
BP S51
EP S51
PG 1
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 205FV
UT WOS:000323429400155
ER
PT J
AU Balshaw, DM
AF Balshaw, D. M.
TI Measuring External Environmental Exposures as Part of the Exposome.
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Meeting Abstract
CT 44th Annual Meeting of the
Environmental-Mutagenesis-and-Genomics-Society (EMGS)
CY SEP 21-25, 2013
CL Monterey, CA
SP Environm Mutagenesis & Genom Soc (EMGS)
C1 [Balshaw, D. M.] NIEHS, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 3
U2 16
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD SEP
PY 2013
VL 54
SU 1
BP S15
EP S15
PG 1
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 205FV
UT WOS:000323429400011
ER
PT J
AU Chan, K
Resnick, M
Gordenin, D
AF Chan, K.
Resnick, M.
Gordenin, D.
TI In Vivo Analysis of Translesion DNA Synthesis-Mediated Bypass of Abasic
Sites and Sulfite-Induced Lesions in Single-Strand DNA.
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Meeting Abstract
CT 44th Annual Meeting of the
Environmental-Mutagenesis-and-Genomics-Society (EMGS)
CY SEP 21-25, 2013
CL Monterey, CA
SP Environm Mutagenesis & Genom Soc (EMGS)
C1 [Chan, K.; Resnick, M.; Gordenin, D.] NIEHS, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD SEP
PY 2013
VL 54
SU 1
BP S51
EP S51
PG 1
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 205FV
UT WOS:000323429400158
ER
PT J
AU Heindel, J
AF Heindel, J.
TI Prenatal Exposures to Environmental Pollutants, Epigenetics, and
Children's Health.
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Meeting Abstract
CT 44th Annual Meeting of the
Environmental-Mutagenesis-and-Genomics-Society (EMGS)
CY SEP 21-25, 2013
CL Monterey, CA
SP Environm Mutagenesis & Genom Soc (EMGS)
C1 [Heindel, J.] NIEHS, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD SEP
PY 2013
VL 54
SU 1
BP S16
EP S16
PG 1
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 205FV
UT WOS:000323429400018
ER
PT J
AU Hernandez-Ramon, EE
Wise, JP
Si, N
Wise, SS
Wise, JP
Poirier, MC
AF Hernandez-Ramon, E. E.
Wise, Sr J. P.
Si, N.
Wise, S. S.
Wise, Jr J. P.
Poirier, M. C.
TI Detection of Polycyclic Aromatic Hydrocarbon (PAH)-DNA Adducts in
Epidermis from Sperm Whales (Physeter macrocephalus) in the Gulf of
Mexico.
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Meeting Abstract
CT 44th Annual Meeting of the
Environmental-Mutagenesis-and-Genomics-Society (EMGS)
CY SEP 21-25, 2013
CL Monterey, CA
SP Environm Mutagenesis & Genom Soc (EMGS)
C1 [Hernandez-Ramon, E. E.; Si, N.; Poirier, M. C.] NCI, Carcinogen DNA Interact Sect, LCBG, CCR,NIH, Bethesda, MD 20892 USA.
[Wise, Sr J. P.; Wise, S. S.; Wise, Jr J. P.] Univ So Maine, Dept Appl Sci Med, Wise Lab Environm & Genet Toxicol, Maine Ctr Toxicol & Environm Hlth, Portland, ME 04103 USA.
NR 0
TC 0
Z9 0
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD SEP
PY 2013
VL 54
SU 1
BP S50
EP S50
PG 1
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 205FV
UT WOS:000323429400154
ER
PT J
AU Hobbs, CA
Mercado-Feliciano, M
Cora, MC
McIntyre, BS
Stout, MD
Foster, PM
Shepard, KG
Swartz, CD
Garantziotis, S
Witt, KL
Smith-Roe, SL
AF Hobbs, C. A.
Mercado-Feliciano, M.
Cora, M. C.
McIntyre, B. S.
Stout, M. D.
Foster, P. M.
Shepard, K. G.
Swartz, C. D.
Garantziotis, S.
Witt, K. L.
Smith-Roe, S. L.
TI Black Cohosh Extract is Genotoxic in Rodents and Induces Hematological
Changes Associated with Disruption of Folate Metabolism
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Meeting Abstract
CT 44th Annual Meeting of the
Environmental-Mutagenesis-and-Genomics-Society (EMGS)
CY SEP 21-25, 2013
CL Monterey, CA
SP Environm Mutagenesis & Genom Soc (EMGS)
C1 [Hobbs, C. A.; Shepard, K. G.; Swartz, C. D.] ILS Inc, Genet & Mol Toxicol Div, Res Triangle Pk, NC USA.
[Mercado-Feliciano, M.; Cora, M. C.; McIntyre, B. S.; Stout, M. D.; Foster, P. M.; Witt, K. L.; Smith-Roe, S. L.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Garantziotis, S.] NIEHS, Clin Res Program, Res Triangle Pk, NC 27709 USA.
[Mercado-Feliciano, M.] US EPA, Div Hlth Effects, Off Pesticide Programs, Washington, DC 20460 USA.
RI Garantziotis, Stavros/A-6903-2009
OI Garantziotis, Stavros/0000-0003-4007-375X
NR 0
TC 0
Z9 0
U1 1
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD SEP
PY 2013
VL 54
SU 1
BP S27
EP S27
PG 1
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 205FV
UT WOS:000323429400059
ER
PT J
AU McHale, C
Thomas, R
Lan, Q
Hubbard, A
Zhang, L
Vermeulen, R
Li, G
Rappaport, S
Yin, S
Rothman, N
Smith, M
AF McHale, C.
Thomas, R.
Lan, Q.
Hubbard, A.
Zhang, L.
Vermeulen, R.
Li, G.
Rappaport, S.
Yin, S.
Rothman, N.
Smith, M.
TI Analysis of Global Gene Expression in Benzene-Exposed and Control
Workers by RNA-Sequencing: A Pilot Study.
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Meeting Abstract
CT 44th Annual Meeting of the
Environmental-Mutagenesis-and-Genomics-Society (EMGS)
CY SEP 21-25, 2013
CL Monterey, CA
SP Environm Mutagenesis & Genom Soc (EMGS)
C1 [McHale, C.; Thomas, R.; Hubbard, A.; Zhang, L.; Rappaport, S.; Smith, M.] Univ Calif Berkeley, Berkeley, CA 94720 USA.
[Lan, Q.; Rothman, N.] NCI, Bethesda, MD 20892 USA.
[Vermeulen, R.] Univ Utrecht, Utercht, Netherlands.
[Li, G.; Yin, S.] China Ctr Dis Control, Beijing, Peoples R China.
NR 0
TC 0
Z9 0
U1 1
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD SEP
PY 2013
VL 54
SU 1
BP S40
EP S40
PG 1
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 205FV
UT WOS:000323429400113
ER
PT J
AU Rivera, AV
Sanchez, VC
Poirier, MC
Olivero, OA
AF Rivera, A., V
Sanchez, V. C.
Poirier, M. C.
Olivero, O. A.
TI A Novel Mechanism of Zidovudine-Induced Cytotoxicity Involves Abnormal
Polymerization of alpha and beta-Tubulin.
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Meeting Abstract
CT 44th Annual Meeting of the
Environmental-Mutagenesis-and-Genomics-Society (EMGS)
CY SEP 21-25, 2013
CL Monterey, CA
SP Environm Mutagenesis & Genom Soc (EMGS)
C1 [Rivera, A., V; Poirier, M. C.; Olivero, O. A.] NCI, Carcinogen DNA Interact, NIH, Bethesda, MD 20892 USA.
[Sanchez, V. C.] In Vitro Pathogenesis, Bethesda, MD 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 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD SEP
PY 2013
VL 54
SU 1
BP S39
EP S39
PG 1
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 205FV
UT WOS:000323429400109
ER
PT J
AU Swartz, C
Green, A
Garibaldi, P
Recio, L
Witt, K
AF Swartz, C.
Green, A.
Garibaldi, P.
Recio, L.
Witt, K.
TI Results of Genotoxicity Testing of Drinking Water Contaminants
Demonstrates the Importance of Using a Broad Test Battery
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Meeting Abstract
CT 44th Annual Meeting of the
Environmental-Mutagenesis-and-Genomics-Society (EMGS)
CY SEP 21-25, 2013
CL Monterey, CA
SP Environm Mutagenesis & Genom Soc (EMGS)
C1 [Swartz, C.; Green, A.; Garibaldi, P.; Recio, L.] Integrated Syst Lab, Res Triangle Pk, NC USA.
[Witt, K.] NIEHS, Res Triangle Pk, NC 27709 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 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD SEP
PY 2013
VL 54
SU 1
BP S49
EP S49
PG 1
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 205FV
UT WOS:000323429400150
ER
PT J
AU Wilson, SH
AF Wilson, S. H.
TI Understanding Step-to-Step Coordination during Base Lesion DNA Repair.
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Meeting Abstract
CT 44th Annual Meeting of the
Environmental-Mutagenesis-and-Genomics-Society (EMGS)
CY SEP 21-25, 2013
CL Monterey, CA
SP Environm Mutagenesis & Genom Soc (EMGS)
C1 [Wilson, S. H.] NIEHS, NIH, Res Triangle Pk, NC 27709 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 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD SEP
PY 2013
VL 54
SU 1
BP S22
EP S22
PG 1
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 205FV
UT WOS:000323429400042
ER
PT J
AU Suren, P
Stoltenberg, C
Bresnahan, M
Hirtz, D
Lie, KK
Lipkin, WI
Magnus, P
Reichborn-Kjennerud, T
Schjolberg, S
Susser, E
Oyen, AS
Li, L
Hornig, M
AF Suren, Pal
Stoltenberg, Camilla
Bresnahan, Michaeline
Hirtz, Deborah
Lie, Kari Kveim
Lipkin, W. Ian
Magnus, Per
Reichborn-Kjennerud, Ted
Schjolberg, Synnve
Susser, Ezra
Oyen, Anne-Siri
Li, Leah
Hornig, Mady
TI Early Growth Patterns in Children with Autism
SO EPIDEMIOLOGY
LA English
DT Article
AB Background: Case-control studies have found increased head growth during the first year of life in children with autism spectrum disorder. Length and weight have not been as extensively studied, and there are few studies of population-based samples.
Methods: The study was conducted in a sample of 106,082 children from the population-based Norwegian Mother and Child Cohort. The children were born in 1999-2009; by the end of follow-up on 31 December 2012, the age range was 3.6 through 13.1 years (mean 7.4 years). Measures were obtained prospectively until age 12 months for head circumference and 36 months for length and weight. We compared growth trajectories in autism spectrum disorder cases and noncases using Reed first-order models.
Results: Subjects included 376 children (310 boys and 66 girls) with specialist-confirmed autism spectrum disorder. In boys with autism spectrum disorder, mean head growth was similar to that of other boys, but variability was greater, and 8.7% had macrocephaly (head circumference >97th cohort percentile) by 12 months of age. Autism spectrum disorder boys also had slightly increased body growth, with mean length 1.1cm above and mean weight 300g above the cohort mean for boys at age 12 months. Throughout the first year, the head circumference of girls with autism spectrum disorder was reduced by 0.3cm at birth and 0.5cm at 12 months. Their mean length was similar to that of other girls, but their mean weight was 150-350g below at all ages from birth to 3 years. The reductions in mean head circumference and weight in girls with autism spectrum disorder appear to be driven by those with intellectual disability, genetic disorders, and epilepsy.
Discussion: Growth trajectories in children with autism spectrum disorder diverge from those of other children and the differences are sex specific. Previous findings of increased mean head growth were not replicated.
C1 [Suren, Pal; Li, Leah] UCL Inst Child Hlth, Ctr Paediat Epidemiol & Biostat, London, England.
[Suren, Pal; Stoltenberg, Camilla; Lie, Kari Kveim; Magnus, Per; Reichborn-Kjennerud, Ted; Schjolberg, Synnve; Oyen, Anne-Siri] Norwegian Inst Publ Hlth, N-0403 Oslo, Norway.
[Bresnahan, Michaeline; Lipkin, W. Ian; Susser, Ezra; Hornig, Mady] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA.
[Bresnahan, Michaeline; Susser, Ezra] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Hirtz, Deborah] NINDS, Bethesda, MD 20892 USA.
[Reichborn-Kjennerud, Ted] Univ Oslo, Inst Psychiat, Oslo, Norway.
[Oyen, Anne-Siri] Lovisenberg Hosp, Nic Waals Inst, Oslo, Norway.
RP Suren, P (reprint author), Norwegian Inst Publ Hlth, POB 4404 Nydalen, N-0403 Oslo, Norway.
EM pal.suren@fhi.no
FU Norwegian Ministry of Health and Care Services; Norwegian Ministry of
Education and Research; Research Council of Norway/FUGE [151918];
National Institute of Neurological Disorders and Stroke (NIH/NINDS),
Bethesda [NS47537]; National Institute of Environmental Health Sciences
(NIH/NIEHS), Research Triangle Park, NC [NO-ES-75558]; NINDS [NS47537
[Lipkin]]; Research Council of Norway [185476, 190694]; UK Medical
Research Council (MRC) Career Development Award in Biostatistics; MRC
FX The Norwegian Mother and Child Cohort is supported by the Norwegian
Ministry of Health and Care Services, the Norwegian Ministry of
Education and Research, the Research Council of Norway/FUGE (grant
151918), the National Institute of Neurological Disorders and Stroke
(NIH/NINDS), Bethesda (grant NS47537), and the National Institute of
Environmental Health Sciences (NIH/NIEHS), Research Triangle Park, NC
(contract NO-ES-75558). The Autism Birth Cohort study is funded by the
NINDS (grant NS47537 [Lipkin]). P.S. is funded by the Research Council
of Norway, grant numbers 185476 and 190694. L.L. is funded by a UK
Medical Research Council (MRC) Career Development Award in
Biostatistics. The Centre for Paediatric Epidemiology and Biostatistics
is supported by the MRC in its capacity as the MRC Centre of
Epidemiology for Child Health.
NR 36
TC 18
Z9 18
U1 1
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD SEP
PY 2013
VL 24
IS 5
BP 660
EP 670
DI 10.1097/EDE.0b013e31829e1d45
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 200YL
UT WOS:000323107600006
PM 23867813
ER
PT J
AU Menke, A
Orchard, TJ
Imperatore, G
Bullard, KM
Mayer-Davis, E
Cowie, CC
AF Menke, Andy
Orchard, Trevor J.
Imperatore, Giuseppina
Bullard, Kai McKeever
Mayer-Davis, Elizabeth
Cowie, Catherine C.
TI The Prevalence of Type 1 Diabetes in the United States
SO EPIDEMIOLOGY
LA English
DT Letter
C1 [Menke, Andy] Social & Sci Syst Inc, Silver Spring, MD USA.
[Orchard, Trevor J.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Imperatore, Giuseppina; Bullard, Kai McKeever] Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Diabet Translat, Atlanta, GA USA.
[Mayer-Davis, Elizabeth] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA.
[Cowie, Catherine C.] NIDDK, NIH, Bethesda, MD USA.
RP Menke, A (reprint author), Social & Sci Syst Inc, Silver Spring, MD USA.
EM amenke@s-3.com
OI orchard, trevor/0000-0001-9552-3215
FU Intramural CDC HHS [CC999999]; PHS HHS [GS10F0381L]
NR 8
TC 15
Z9 15
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD SEP
PY 2013
VL 24
IS 5
BP 773
EP 774
DI 10.1097/EDE.0b013e31829ef01a
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 200YL
UT WOS:000323107600019
PM 23903880
ER
PT J
AU Rahu, K
Hakulinen, T
Smailyte, G
Stengrevics, A
Auvinen, A
Inskip, PD
Boice, JD
Rahu, M
AF Rahu, Kaja
Hakulinen, Timo
Smailyte, Giedre
Stengrevics, Aivars
Auvinen, Anssi
Inskip, Peter D.
Boice, John D., Jr.
Rahu, Mati
TI Site-specific cancer risk in the Baltic cohort of Chernobyl cleanup
workers, 1986-2007
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Article
DE Chernobyl nuclear accident; Neoplasms; Incidence; Radiation effects;
Estonia; Latvia; Lithuania
ID THYROID-CANCER; LIQUIDATORS; ESTONIA; CONSEQUENCES; MORTALITY; LATVIA
AB Objective: To assess site-specific cancer risk in the Baltic cohort of Chernobyl cleanup workers, 1986-2007.
Methods: The Baltic cohort includes 17,040 men from Estonia, Latvia and Lithuania who participated in the environmental cleanup after the accident at the Chernobyl Nuclear Power Station in 1986-1991 and who were followed up for cancer incidence until the end of 2007. Cancer cases diagnosed in the cohort and in the male population of each country were identified from the respective national cancer registers. The proportional incidence ratio (PIR) with 95% confidence interval (CI) was used to estimate the site-specific cancer risk in the cohort. For comparison and as it was possible, the site-specific standardised incidence ratio (SIR) was calculated for the Estonian sub-cohort, which was not feasible for the other countries.
Results: Overall, 756 cancer cases were reported during 1986-2007. A higher proportion of thyroid cancers in relation to the male population was found (PIR = 2.76; 95% CI 1.63-4.36), especially among those who started their mission shortly after the accident, in April-May 1986 (PIR = 6.38; 95% CI 2.34-13.89). Also, an excess of oesophageal cancers was noted (PIR = 1.52; 95% CI 1.06-2.11). No increased PIRs for leukaemia or radiation-related cancer sites combined were observed. PIRs and SIRs for the Estonian sub-cohort demonstrated the same site-specific cancer risk pattern.
Conclusion: Consistent evidence of an increase in radiation-related cancers in the Baltic cohort was not observed with the possible exception of thyroid cancer, where conclusions are hampered by known medical examination including thyroid screening among cleanup workers. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Rahu, Kaja; Rahu, Mati] Natl Inst Hlth Dev, Dept Epidemiol & Biostat, EE-11619 Tallinn, Estonia.
[Hakulinen, Timo] Finnish Canc Registry, FIN-00170 Helsinki, Finland.
[Smailyte, Giedre] Vilnius Univ, Inst Oncol, Lithuanian Canc Registry, Vilnius, Lithuania.
[Stengrevics, Aivars] Latvian Canc Registry, Riga, Latvia.
[Auvinen, Anssi] Univ Tampere, Sch Hlth Sci, FIN-33101 Tampere, Finland.
[Auvinen, Anssi] Radiat & Nucl Safety Author, Helsinki, Finland.
[Inskip, Peter D.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Boice, John D., Jr.] Natl Council Radiat Protect & Measurements, Bethesda, MD USA.
[Boice, John D., Jr.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.
RP Rahu, K (reprint author), Natl Inst Hlth Dev, Hiiu 42, EE-11619 Tallinn, Estonia.
EM kaja.rahu@tai.ee
RI Rahu, Mati/A-9981-2008;
OI Auvinen, Anssi/0000-0003-1125-4818
FU Estonian Ministry of Education and Science [SF0940026s07]; Estonian
Research Council [IUT5-1]; National Institutes of Health, National
Cancer Institute, Division of Cancer Epidemiology and Genetics; US
National Cancer Institute [N01-CP-85638-03]
FX This study was supported financially by the Estonian Ministry of
Education and Science (target funding SF0940026s07), the Estonian
Research Council (IUT5-1) and the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Division of
Cancer Epidemiology and Genetics. The initial work was financed by US
National Cancer Institute Contract N01-CP-85638-03.
NR 33
TC 8
Z9 10
U1 1
U2 21
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD SEP
PY 2013
VL 49
IS 13
BP 2926
EP 2933
DI 10.1016/j.ejca.2013.04.014
PG 8
WC Oncology
SC Oncology
GA 194JD
UT WOS:000322627300019
PM 23683549
ER
PT J
AU Ghayee, HK
Giubellino, A
Click, A
Kapur, P
Christie, A
Xie, XJ
Martucci, V
Shay, JW
Souza, RF
Pacak, K
AF Ghayee, Hans K.
Giubellino, Alessio
Click, Arielle
Kapur, Payal
Christie, Alana
Xie, Xian-Jin
Martucci, Victoria
Shay, Jerry W.
Souza, Rhonda F.
Pacak, Karel
TI Phospho-mTOR is not upregulated in metastatic SDHB paragangliomas
SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
DE Paraganglioma; pmTOR; SDHB
ID NEUROENDOCRINE TUMORS; PHEOCHROMOCYTOMA; EVEROLIMUS; MUTATIONS; GROWTH;
HYPOXIA; RAD001
AB Background Pheochromocytomas (PCCs)/paragangliomas (PGLs) are neuroendocrine tumours that may cause arrhythmia and death if untreated. Treatment for patients with metastatic tumours is lacking. As new PCC/PGL susceptibility genes are discovered that are associated with the mTOR pathway, treatment targets focusing on this pathway are being intensively explored.
Design Twenty-one human PCC/PGLs were analysed from two tertiary care centres. Immunohistochemistry (IHC) analysis was performed for phospho-mTOR (pmTOR), phospho-S6K (pS6K), phosphoinositide 3-kinase (PI3K), phospho-4EBP1 (p4EBP1), HIF1 alpha and MIB-1 in 6 metastatic SDHB PCC/PGLs, 15 nonmetastatic PCC/PGLs, (including 1 TMEM127 PCC and 1 nonmetastatic SDHB PGL) and 6 normal adrenal medullas. The product of the intensity of stain and percentage of cells stained was calculated as an H score.
Results Using a two-sample t-test and paired t-test, pmTOR and pS6K had significantly higher H scores in nonmetastatic PCC/PGLs than in metastatic SDHB PCC/PGLs. HIF1 alpha had significantly higher H scores in metastatic SDHB PCC/PGLs compared with nonmetastatic PCC/PGLs and normal adrenal medulla. No difference in H scores was seen with p4EBP1, PI3K and MIB-1 when comparing metastatic SDHB PCC/PGLs and nonmetastatic PCC/PGLs. Significantly higher difference in pS6K was seen in normal adrenal medullas compared to nonmetastatic PCC/PGLs and metastatic SDHB PCC/PGLs.
Conclusion The present results suggest that the use of mTOR inhibitors alone for metastatic SDHB PCC/PGLs may not achieve good therapeutic efficacy in patients.
C1 [Ghayee, Hans K.; Souza, Rhonda F.] Univ Texas SW Med Ctr Dallas, VA North Texas Hlth Care Syst, Dept Internal Med, Dallas, TX 75235 USA.
[Giubellino, Alessio; Martucci, Victoria; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
[Click, Arielle; Shay, Jerry W.] Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75235 USA.
[Kapur, Payal] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75235 USA.
[Christie, Alana; Xie, Xian-Jin] Univ Texas SW Med Ctr Dallas, Simmons Canc Ctr, Dallas, TX 75235 USA.
[Xie, Xian-Jin] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75235 USA.
RP Pacak, K (reprint author), Eunice Kennedy Shriver NICHD, Sect Med Neuroendocrinol, NIH, CRC, Bldg 10,Room 1E-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA.
EM karel@mail.nih.gov
FU North American Neuroendocrine Tumor Society (NANETS); American Cancer
Society University of Texas Southwestern Institutional Grant
FX The authors are grateful to Amita Kathuria, MD at the University of
Texas Southwestern Medical Center for helpful discussions and for
reviewing this manuscript. This study was funded by the North American
Neuroendocrine Tumor Society (NANETS) and the American Cancer Society
University of Texas Southwestern Institutional Grant (to HKG).
NR 22
TC 5
Z9 5
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-2972
J9 EUR J CLIN INVEST
JI Eur. J. Clin. Invest.
PD SEP
PY 2013
VL 43
IS 9
BP 970
EP 977
DI 10.1111/eci.12127
PG 8
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 201PA
UT WOS:000323152800010
PM 23889685
ER
PT J
AU Klabunde, CN
Willis, GB
Casalino, LP
AF Klabunde, Carrie N.
Willis, Gordon B.
Casalino, Lawrence P.
TI Facilitators and Barriers to Survey Participation by Physicians: A Call
to Action for Researchers
SO EVALUATION & THE HEALTH PROFESSIONS
LA English
DT Article
DE survey; physician; response rates; qualitative research; clinicians
ID RESPONSE RATES; MEDICAL GROUPS
AB Surveys of health care providers are a well-established tool for obtaining information about the organization and delivery of care as well as about provider knowledge and attitudes. However, declining response rates to provider surveys are a widely acknowledged concern. Although a number of studies have identified specific methods for increasing response rates in health care providerand particularly physiciansurveys, few have addressed the more fundamental question of what motivates or deters providers from survey participation. We briefly review theoretical perspectives concerning why providers choose to participate in surveys, and what is known about facilitators and barriers to participation. We then describe several research designs (i.e., focus groups, key informant interviews, diary and office workflow studies, surveying the surveyors, and follow-back studies of respondents/nonrespondents) for obtaining empirical data on facilitators and barriers to survey participation, particularly by physicians and medical groups. Researchers must begin to build an evidence base for understanding provider decisions concerning survey participation.
C1 [Klabunde, Carrie N.; Willis, Gordon B.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Casalino, Lawrence P.] Weill Cornell Med Coll, Dept Publ Hlth, Div Outcomes & Effectiveness Res, New York, NY USA.
RP Klabunde, CN (reprint author), NCI, Appl Res Program, Div Canc Control & Populat Sci, EPN 4005,6130 Execut Blvd, Bethesda, MD 20892 USA.
EM KlabundC@mail.nih.gov
NR 31
TC 16
Z9 16
U1 0
U2 17
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0163-2787
J9 EVAL HEALTH PROF
JI Eval. Health Prof.
PD SEP
PY 2013
VL 36
IS 3
SI SI
BP 279
EP 295
DI 10.1177/0163278713496426
PG 17
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 205HK
UT WOS:000323434100002
PM 23975758
ER
PT J
AU Kranick, SM
Hallett, M
AF Kranick, Sarah M.
Hallett, Mark
TI Neurology of volition
SO EXPERIMENTAL BRAIN RESEARCH
LA English
DT Review
DE Volition; Agency; Will; Movement disorders; Psychogenic; Anosognosia;
Alien hand; Passivity phenomena
ID LA-TOURETTE SYNDROME; MOVEMENT-RELATED POTENTIALS; MOTOR CONVERSION
DISORDER; ALIEN HAND SYNDROME; HUNTINGTONS-DISEASE; UTILIZATION
BEHAVIOR; VOLUNTARY MOVEMENT; SENSORY CONSEQUENCES; PSYCHOGENIC TREMOR;
STRUCTURAL-CHANGES
AB Neurological disorders of volition may be characterized by deficits in willing and/or agency. When we move our bodies through space, it is the sense that we intended to move (willing) and that our actions were a consequence of this intention (self-agency) that gives us the sense of voluntariness and a general feeling of being "in control." While it is possible to have movements that share executive machinery ordinarily used for voluntary movement but lack a sense of voluntariness, such as psychogenic movement disorders, it is also possible to claim volition for presumed involuntary movements (early chorea) or even when no movement is produced (anosognosia). The study of such patients should enlighten traditional models of how the percepts of volition are generated in the brain with regard to movement. We discuss volition and its components as multi-leveled processes with feedforward and feedback information flow, and dependence on prior expectations as well as external and internal cues.
C1 [Kranick, Sarah M.; Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA.
RP Kranick, SM (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, 10-6-5700,10 Ctr Dr,MSC 1430, Bethesda, MD 20892 USA.
EM sarah.kranick@nih.gov
FU NINDS Intramural Program
FX This research was supported by the NINDS Intramural Program.
NR 83
TC 8
Z9 9
U1 8
U2 30
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0014-4819
J9 EXP BRAIN RES
JI Exp. Brain Res.
PD SEP
PY 2013
VL 229
IS 3
BP 313
EP 327
DI 10.1007/s00221-013-3399-2
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA 203IY
UT WOS:000323287000004
PM 23329204
ER
PT J
AU Beinart, R
Khurram, IM
Liu, ST
Yarmohammadi, H
Halperin, HR
Bluemke, DA
Gai, N
van der Geest, RJ
Lima, JAC
Calkins, H
Zimmerman, SL
Nazarian, S
AF Beinart, Roy
Khurram, Irfan M.
Liu, Songtao
Yarmohammadi, Hirad
Halperin, Henry R.
Bluemke, David A.
Gai, Neville
van der Geest, Rob J.
Lima, Joao A. C.
Calkins, Hugh
Zimmerman, Stefan L.
Nazarian, Saman
TI Cardiac magnetic resonance T1 mapping of left atrial myocardium
SO HEART RHYTHM
LA English
DT Article
DE Atrial fibrillation; Cardiac magnetic resonance; T1 mapping; Left atrial
fibrosis; Late gadolinium enhancement
ID CATHETER ABLATION; DELAYED-ENHANCEMENT; PULMONARY VEIN; FIBRILLATION;
FIBROSIS; MRI; CARDIOMYOPATHY; DISEASE; DYSFUNCTION; ASSOCIATION
AB BACKGROUND Cardiac magnetic resonance (CMR) T1 mapping is an emerging tool for objective quantification of myocardial fibrosis.
OBJECTIVES To (a) establish the feasibility of left atrial (LA) T1 measurements, (b) determine the range of LA T1 values in patients with atrial fibrillation (AF) vs healthy volunteers, and (c) validate T1 mapping vs LA intracardiac electrogram voltage amplitude measures.
METHODS CMR imaging at 1.5 T was performed in 51 consecutive patients before AF ablation and in 16 healthy volunteers. T1 measurements were obtained from the posterior LA myocardium by using the modified Look-Locker inversion-recovery sequence. Given the established association of reduced electrogram amplitude with fibrosis, intracardiac point-by-point bipolar LA voltage measures were recorded for the validation of T1 measurements.
RESULTS The median LA T1 relaxation time was shorter in patients with AF (387 [interquartile range 364-428] ms) compared to healthy volunteers (459 [interquartile range 418-532] ms; P < .001) and was shorter in patients with AF with prior ablation compared to patients without prior ablation (P = .035). In a generalized estimating equations model., adjusting for data clusters per participant, age, rhythm during CMR, prior ablation, AF type, hypertension, and diabetes, each 100-ms increase in T1 relaxation time was associated with 0.1 mV increase in intracardiac bipolar LA voltage (P = .025).
CONCLUSIONS Measurement of the LA myocardium T1 relaxation time is feasible and strongly associated with invasive voltage measures. This methodology may improve the quantification of fibrotic changes in thin-walled myocardial tissues.
C1 [Beinart, Roy; Khurram, Irfan M.; Yarmohammadi, Hirad; Halperin, Henry R.; Lima, Joao A. C.; Calkins, Hugh; Nazarian, Saman] Johns Hopkins Univ Hosp, Div Cardiol, Baltimore, MD 21287 USA.
[Liu, Songtao; Bluemke, David A.; Gai, Neville] NIH, Bethesda, MD 20892 USA.
[van der Geest, Rob J.] Leiden Univ, Dept Radiol, Leiden, Netherlands.
[Zimmerman, Stefan L.] Johns Hopkins Univ Hosp, Dept Radiol, Baltimore, MD 21287 USA.
RP Beinart, R (reprint author), Johns Hopkins Univ Hosp, 702 Rutland Ave,Traylor 903, Baltimore, MD 21287 USA.
EM rbeiner1@jhmi.edu
RI van der Geest, Rob/J-8193-2015;
OI van der Geest, Rob/0000-0002-9084-5597; Bluemke,
David/0000-0002-8323-8086
FU National Institutes of Health [K23HL089333]; Dr Francis P. Chiaramonte
Foundation; Norbert and Louise Grunwald Cardiac Arrhythmia Research
Fund; Biosense Webste
FX The study was funded by National Institutes of Health grant K23HL089333
(to Dr Nazarian) and by the Dr Francis P. Chiaramonte Foundation and the
Norbert and Louise Grunwald Cardiac Arrhythmia Research Fund. Dr
Nazarian is on the MRI Advisory Panel (unpaid) for Medtronic and is a
scientific advisor to Biosense Webster; he is also the principal
investigator for research funding awarded to Johns Hopkins from Biosense
Webster and from the National Institutes of Health (K23HL089333). Dr van
der Geest is a consultant to Medis Medical Imaging Systems.
NR 34
TC 31
Z9 31
U1 3
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1547-5271
J9 HEART RHYTHM
JI Heart Rhythm
PD SEP
PY 2013
VL 10
IS 9
BP 1325
EP 1331
DI 10.1016/j.hrthm.2013.01.003
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 206CQ
UT WOS:000323494600021
PM 23643513
ER
PT J
AU Nugent, AC
Luckenbaugh, DA
Wood, SE
Bogers, W
Zarate, CA
Drevets, WC
AF Nugent, Allison C.
Luckenbaugh, David A.
Wood, Suzanne E.
Bogers, Wendy
Zarate, Carlos A., Jr.
Drevets, Wayne C.
TI Automated subcortical segmentation using FIRST: Test-retest reliability,
interscanner reliability, and comparison to manual segmentation
SO HUMAN BRAIN MAPPING
LA English
DT Article
DE brain; volume; amygdale; hippocampus; caudate; putamen; pallidum;
accumbens; thalamus
ID BIPOLAR DISORDER; MOOD DISORDERS; BRAIN VOLUMES; MRI
AB Multiple techniques exist for the automated segmentation of magnetic resonance images (MRIs). The validity of these techniques can be assessed by evaluating test-retest reliability, interscanner reliability, and consistency with manual segmentation. We evaluate these measures for the FSL/FIRST subcortical segmentation tool. We retrospectively analyzed 190 MRI scans from 87 subjects with mood or anxiety disorders and healthy volunteers scanned multiple times on different platforms (N = 56) and/or the same platform (N = 45, groups overlap), and 146 scans from subjects who underwent both high-resolution and whole brain imaging in a single session, for comparison with manual segmentation of the hippocampus. The thalamus, caudate, putamen, hippocampus, and pallidum were reliably segmented in different sessions on the same scanner (Intraclass correlation coefficient (ICC) > 0.83 scanners and diagnostic groups pooled). In these regions, the range of between platform reliabilities were lower (0.527 < ICC < 0.953), although values below 0.7 were due to systematic differences between platforms or low reliability in the hippocampus between eight- and single-channel coil platforms. Accumbens and amygdala segmentations were generally unreliable within and between scanning platforms. ICC values for hippocampal volumes between automated and manual segmentations were acceptable (ICC > 0.7, groups pooled), and both methods detected significant differences between genders. In addition, FIRST segmentations were consistent with manual segmentations (in a subset of images; N = 20) in the left caudate and bilateral putamen. This retrospective analysis assesses realistic performance of the algorithm in conditions like those found in multisite trials or meta-analyses. In addition, the inclusion of psychiatric patients establishes reliability in subjects exhibiting volumetric abnormalities, validating patient studies. Hum Brain Mapp 34:2313-2329, 2013. (c) 2012 Wiley Periodicals, Inc.
C1 [Nugent, Allison C.; Luckenbaugh, David A.; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA.
[Wood, Suzanne E.] Temple Univ, Sch Med, Philadelphia, PA 19122 USA.
[Bogers, Wendy; Drevets, Wayne C.] Univ Oklahoma, Coll Med, Dept Psychiat, Laureate Inst Brain Res, Tulsa, OK USA.
RP Nugent, AC (reprint author), NIMH, Sect Neuroimaging Mood Disorders, Expt Therapeut & Pathophysiol Branch, NIH, 10 Ctr Dr,MSC 1030, Bethesda, MD 20892 USA.
EM nugenta@mail.nih.gov
OI Nugent, Allison/0000-0003-2569-2480
FU NIMH (Intramural Research Program)
FX Contract grant sponsor: NIMH (Intramural Research Program).
NR 18
TC 33
Z9 33
U1 1
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 SEP
PY 2013
VL 34
IS 9
BP 2313
EP 2329
DI 10.1002/hbm.22068
PG 17
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 203UZ
UT WOS:000323320800026
PM 22815187
ER
PT J
AU You, XZ
Adjouadi, M
Wang, J
Guillen, MR
Bernal, B
Sullivan, J
Donner, E
Bjornson, B
Berl, M
Gaillard, WD
AF You, Xiaozhen
Adjouadi, Malek
Wang, Jin
Guillen, Magno R.
Bernal, Byron
Sullivan, Joseph
Donner, Elizabeth
Bjornson, Bruce
Berl, Madison
Gaillard, William D.
TI A decisional space for fMRI pattern separation using the principal
component analysisa comparative study of language networks in pediatric
epilepsy
SO HUMAN BRAIN MAPPING
LA English
DT Article
DE brain activation pattern; data-driven clustering; fMRI; epilepsy;
language; lateralization indices; PCA-based decisional space; visual
rating
ID INTRACAROTID AMOBARBITAL PROCEDURE; FUNCTIONAL MRI; WADA TEST; CEREBRAL
LATERALIZATION; BRAIN INJURY; DOMINANCE; ACTIVATION; HANDEDNESS;
LOCALIZATION; PEOPLE
AB Atypical functional magnetic resonance imaging (fMRI) language patterns may be identified by visual inspection or by region of interest (ROI)-based laterality indices (LI) but are constrained by a priori assumptions. We compared a data-driven novel application of principal component analysis (PCA) to conventional methods. We studied 122 fMRI data sets from control and localization-related epilepsy patients provided by five children's hospitals. Each subject performed an auditory description decision task. The data sets, acquired with different scanners but similar acquisition parameters, were processed through fMRIB software library to obtain 3D activation maps in standard space. A PCA analysis was applied to generate the decisional space and the data cluster into three distinct activation patterns. The classified activation maps were interpreted by (1) blinded reader rating based on predefined language patterns and (2) by language area ROI-based LI (i.e., fixed threshold vs. bootstrap approaches). The different classification results were compared through inter-rater agreement statistics. The unique decisional space classified activation maps into three clusters (a) lower intensity typical language representation, (b) higher intensity typical, as well as (c) higher intensity atypical representation. Inter-rater agreements among the three raters were excellent (Fleiss = 0.85, P = 0.05). There was substantial to excellent agreement between the conventional visual rating and LI methods ( = 0.69-0.82, P = 0.05). The PCA-based method yielded excellent agreement with conventional methods ( = 0.82, P = 0.05). The automated and data-driven PCA decisional space segregates language-related activation patterns in excellent agreement with current clinical rating and ROI-based methods. Hum Brain Mapp 34:2330-2342, 2013. (c) 2012 Wiley Periodicals, Inc.
C1 [You, Xiaozhen] Florida Int Univ, Dept Biomed Engn, Miami, FL 33174 USA.
[You, Xiaozhen] Georgetown Univ, Dept Psychol, Washington, DC 20057 USA.
[Adjouadi, Malek; Wang, Jin] Florida Int Univ, Dept Elect & Comp Engn, Miami, FL 33174 USA.
[Guillen, Magno R.; Bernal, Byron] Miami Childrens Hosp, Dept Radiol, Miami, FL USA.
[Sullivan, Joseph] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA.
[Donner, Elizabeth] Hosp Sick Children, Dept Neurol, Toronto, ON M5G 1X8, Canada.
[Bjornson, Bruce] BC Childrens Hosp, Div Neurol, Vancouver, BC, Canada.
[Bjornson, Bruce] Child & Family Res Inst, Vancouver, BC, Canada.
[Berl, Madison; Gaillard, William D.] George Washington Univ, Childrens Natl Med Ctr, Dept Neurosci, Washington, DC USA.
[Gaillard, William D.] Georgetown Univ, Dept Neurol, Washington, DC USA.
[Gaillard, William D.] NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA.
RP Adjouadi, M (reprint author), Florida Int Univ, Coll Engn & Comp, 10555 W Flagler St,EC 2672, Miami, FL 33174 USA.
EM adjouadi@fiu.edu
RI Bjornson, Bruce/A-8616-2010;
OI Bjornson, Bruce/0000-0002-1465-6196; Guilen, Magno/0000-0001-9649-8429
FU American Epilepsy Society [NINDS R01 NS44280]; Children's Research
Institute Avery Award, Intellectual and Developmental Disabilities
Research Center at Children's National Medical Center [NIH IDDRC
P30HD40677]; General Clinic Research Center [NIH GCRC M01-RR13297];
National Science Foundation [HRD-0833093, CNS-0959985, CNS-1042341];
Ware Foundation; Miami Children's Hospital
FX Contract grant sponsor: The American Epilepsy Society; Contract grant
number: NINDS R01 NS44280; Contract grant sponsor: Children's Research
Institute Avery Award, Intellectual and Developmental Disabilities
Research Center at Children's National Medical Center; Contract grant
number: NIH IDDRC P30HD40677; Contract grant sponsor: The General Clinic
Research Center; Contract grant number: NIH GCRC M01-RR13297; Contract
grant sponsor: The National Science Foundation; Contract grant numbers:
HRD-0833093, CNS-0959985, CNS-1042341; Contract grant sponsor: Ware
Foundation and the joint Neuro-Engineering Program with Miami Children's
Hospital.
NR 48
TC 8
Z9 8
U1 0
U2 9
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 SEP
PY 2013
VL 34
IS 9
BP 2330
EP 2342
DI 10.1002/hbm.22069
PG 13
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 203UZ
UT WOS:000323320800027
PM 22461299
ER
PT J
AU Kantor, DB
Palmer, CD
Young, TR
Meng, Y
Gajdos, ZK
Lyon, H
Price, AL
Pollack, S
London, SJ
Loehr, LR
Smith, LJ
Kumar, R
Jacobs, DR
Petrini, MF
O'Connor, GT
White, WB
Papanicolaou, G
Burkart, KM
Heckbert, SR
Barr, RG
Hirschhorn, JN
AF Kantor, David B.
Palmer, Cameron D.
Young, Taylor R.
Meng, Yan
Gajdos, Zofia K.
Lyon, Helen
Price, Alkes L.
Pollack, Samuela
London, Stephanie J.
Loehr, Laura R.
Smith, Lewis J.
Kumar, Rajesh
Jacobs, David R., Jr.
Petrini, Marcy F.
O'Connor, George T.
White, Wendy B.
Papanicolaou, George
Burkart, Kristin M.
Heckbert, Susan R.
Barr, R. Graham
Hirschhorn, Joel N.
TI Replication and fine mapping of asthma-associated loci in individuals of
African ancestry
SO HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; POPULATIONS; METAANALYSIS; VARIANTS;
SUSCEPTIBILITY; EFFICIENT; DISEASE; SAMPLE; GENE
AB Asthma originates from genetic and environmental factors with about half the risk of disease attributable to heritable causes. Genome-wide association studies, mostly in populations of European ancestry, have identified numerous asthma-associated single nucleotide polymorphisms (SNPs). Studies in populations with diverse ancestries allow both for identification of robust associations that replicate across ethnic groups and for improved resolution of associated loci due to different patterns of linkage disequilibrium between ethnic groups. Here we report on an analysis of 745 African-American subjects with asthma and 3,238 African-American control subjects from the Candidate Gene Association Resource (CARe) Consortium, including analysis of SNPs imputed using 1,000 Genomes reference panels and adjustment for local ancestry. We show strong evidence that variation near RAD50/IL13, implicated in studies of European ancestry individuals, replicates in individuals largely of African ancestry. Fine mapping in African ancestry populations also refined the variants of interest for this association. We also provide strong or nominal evidence of replication at loci near ORMDL3/GSDMB, IL1RL1/IL18R1, and 10p14, all previously associated with asthma in European or Japanese populations, but not at the PYHIN1 locus previously reported in studies of African-American samples. These results improve the understanding of asthma genetics and further demonstrate the utility of genetic studies in populations other than those of largely European ancestry.
C1 [Kantor, David B.] Boston Childrens Hosp, Div Crit Care Med, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA.
[Palmer, Cameron D.; Young, Taylor R.; Meng, Yan; Gajdos, Zofia K.; Lyon, Helen; Hirschhorn, Joel N.] Broad Inst, Program Med & Populat Genet, Cambridge Ctr 7, Cambridge, MA 02142 USA.
[Price, Alkes L.; Pollack, Samuela] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Price, Alkes L.; Pollack, Samuela] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[London, Stephanie J.] NIEHS, Div Intramural Res, DHHS, NIH, Res Triangle Pk, NC 27709 USA.
[Loehr, Laura R.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA.
[Smith, Lewis J.] Northwestern Univ, Feinberg Sch Med, Div Pulm & Crit Care Med, Chicago, IL 60611 USA.
[Kumar, Rajesh] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA.
[Jacobs, David R., Jr.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA.
[Petrini, Marcy F.] Univ Mississippi, Med Ctr, Div Pulm Crit Care & Sleep Med, Jackson, MS 39216 USA.
[O'Connor, George T.] Boston Univ, Dept Med, Ctr Pulm, Sch Med, Boston, MA 02118 USA.
[White, Wendy B.] Tougaloo Coll, Tougaloo, MS 39174 USA.
[White, Wendy B.] Jackson Heart Study, Tougaloo, MS 39174 USA.
[Papanicolaou, George] NHLBI, Div Prevent & Populat Sci, NIH, Rockledge Ctr 2, Bethesda, MD 20892 USA.
[Burkart, Kristin M.] Columbia Univ, Coll Phys & Surg, Div Pulm Allergy & Crit Care, New York, NY 10032 USA.
[Heckbert, Susan R.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.
[Barr, R. Graham] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, Dept Med,Coll Phys & Surg, New York, NY 10032 USA.
[Hirschhorn, Joel N.] Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
RP Hirschhorn, JN (reprint author), Broad Inst, Program Med & Populat Genet, Cambridge Ctr 7, Cambridge, MA 02142 USA.
EM david.kantor@childrens.harvard.edu; joelh@broadinstitute.org
OI Smith, Lewis J/0000-0002-4728-1562; O'Connor,
George/0000-0002-6476-3926; London, Stephanie/0000-0003-4911-5290
FU National Heart, Lung, and Blood Institute [HHSN26800625226C,
N01-HC-95170, N01-HC-95171, N01-HC-95172]; National Institutes of Health
[T32 5T32HD040128-09]; American Asthma Foundation; American Medical
Association; NIH, National Institute of Environmental Health Sciences;
University of North Carolina at Chapel Hill [N01-HC-55015,
N01-HC-55018]; Baylor Medical College [N01-HC-55016]; University of
Mississippi Medical Center [N01-HC-55021]; University of Minnesota
[N01-HC-55019, N01-HC-48048, N01-HC-95163]; Johns Hopkins University
[N01-HC-55020, N01-HC-95162, N01-HC-95168]; University of Texas, Houston
[N01-HC-55022]; University of Alabama at Birmingham [N01-HC-48047,
N01-HC- 95095]; 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]; National Institute on Minority Health and
Health Disparities; National Institute on Biomedical Imaging and
Bioengineering; University of Washington [N01-HC-95159]; University of
California, Los Angeles [N01-HC-95160]; Columbia University
[N01-HC-95161]; 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]; NIH
[R01-HL077612, RC1-HL100543, R01-HL093081]
FX This work is supported by Contract HHSN26800625226C from the National
Heart, Lung, and Blood Institute, T32 5T32HD040128-09 from the National
Institutes of Health, the American Asthma Foundation, the American
Medical Association Seed Grant Research Program, and the Intramural
Research Program of the NIH, National Institute of Environmental Health
Sciences. The authors wish to acknowledge the support of the National
Heart, Lung, and Blood Institute and the contributions of the research
institutions, study investigators, field staff, and study participants
in creating the CARe resource for biomedical research. The following
studies, funded by the listed National Institutes of Health grants, were
utilized in this study. Atherosclerosis Risk in Communities (ARIC):
University of North Carolina at Chapel Hill (N01-HC-55015,
N01-HC-55018), Baylor Medical College (N01-HC-55016), University of
Mississippi Medical Center (N01-HC-55021), University of Minnesota
(N01-HC-55019), Johns Hopkins University (N01-HC-55020), University of
Texas, Houston (N01-HC-55022). Coronary Artery Risk in Young Adults:
University of Alabama at Birmingham (N01-HC-48047, N01-HC- 95095),
University of Minnesota (N01-HC-48048), Northwestern University
(N01-HC-48049), Kaiser Foundation Research Institute (N01-HC-48050),
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: Contracts N01-HC-95170,
N01-HC-95171, N01-HC-95172 from the National Heart, Lung, and Blood
Institute and the National Institute on Minority Health and Health
Disparities, with additional support from the National Institute on
Biomedical Imaging and Bioengineering. Multi-Ethnic Study of
Atherosclerosis: University of Washington (N01-HC-95159), University of
California, Los Angeles (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). Pulmonary phenotyping and analyses in
MESA are funded by NIH grants R01-HL077612, RC1-HL100543 and
R01-HL093081.
NR 38
TC 2
Z9 3
U1 0
U2 11
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
J9 HUM GENET
JI Hum. Genet.
PD SEP
PY 2013
VL 132
IS 9
BP 1039
EP 1047
DI 10.1007/s00439-013-1310-7
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 202UW
UT WOS:000323246200006
PM 23666277
ER
PT J
AU Shriner, D
AF Shriner, Daniel
TI Impact of Hardy-Weinberg disequilibrium on post-imputation quality
control
SO HUMAN GENETICS
LA English
DT Letter
C1 NHGRI, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA.
RP Shriner, D (reprint author), NHGRI, Ctr Res Genom & Global Hlth, Bldg 12A,Room 4047,12 South Dr,MSC 5635, Bethesda, MD 20892 USA.
EM shrinerda@mail.nih.gov
FU NCRR NIH HHS [2M01RR010284]; NHGRI NIH HHS [Z01HG200362]; NIGMS NIH HHS
[S06GM008016-320107, S06GM008016-380111]
NR 5
TC 2
Z9 2
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
J9 HUM GENET
JI Hum. Genet.
PD SEP
PY 2013
VL 132
IS 9
BP 1073
EP 1075
DI 10.1007/s00439-013-1336-x
PG 3
WC Genetics & Heredity
SC Genetics & Heredity
GA 202UW
UT WOS:000323246200009
PM 23842951
ER
PT J
AU Nickerson, ML
Im, KM
Misner, KJ
Tan, W
Lou, H
Gold, B
Wells, DW
Bravo, HC
Fredrikson, KM
Harkins, TT
Milos, P
Zbar, B
Linehan, WM
Yeager, M
Andresson, T
Dean, M
Bova, GS
AF Nickerson, Michael L.
Im, Kate M.
Misner, Kevin J.
Tan, Wei
Lou, Hong
Gold, Bert
Wells, David W.
Bravo, Hector C.
Fredrikson, Karin M.
Harkins, Timothy T.
Milos, Patrice
Zbar, Berton
Linehan, W. Marston
Yeager, Meredith
Andresson, Thorkell
Dean, Michael
Bova, G. Steven
TI Somatic Alterations Contributing to Metastasis of a Castration-Resistant
Prostate Cancer
SO HUMAN MUTATION
LA English
DT Article
DE tumor heterogeneity; somatic mutation; metastasis; epigenetic modifiers;
BRCA1; TMPRSS2; ERG; PBRM1; TET2
AB Metastatic castration-resistant prostate cancer (mCRPC) is a lethal disease, and molecular markers that differentiate indolent from aggressive subtypes are needed. We sequenced the exomes of five metastatic tumors and healthy kidney tissue from an index case with mCRPC to identify lesions associated with disease progression and metastasis. An Ashkenazi Jewish (AJ) germline founder mutation, del185AG in BRCA1, was observed and AJ ancestry was confirmed. Sixty-two somatic variants altered proteins in tumors, including cancer-associated genes, TMPRSS2-ERG, PBRM1, and TET2. The majority (n=53) of somatic variants were present in all metastases and only a subset (n=31) was observed in the primary tumor. Integrating tumor next-generation sequencing and DNA copy number showed somatic loss of BRCA1 and TMPRSS2-ERG. We sequenced 19 genes with deleterious mutations in the index case in additional mCRPC samples and detected a frameshift, two somatic missense alterations, tumor loss of heterozygosity, and combinations of germline missense SNPs in TET2. In summary, genetic analysis of metastases from an index case permitted us to infer a chronology for the clonal spread of disease based on sequential accrual of somatic lesions. The role of TET2 in mCRPC deserves additional analysis and may define a subset of metastatic disease. Published 2013 Wiley Periodicals, Inc.
C1 [Nickerson, Michael L.; Im, Kate M.; Misner, Kevin J.; Gold, Bert; Zbar, Berton; Dean, Michael] NCI, Canc & Inflammat Program, NIH, Frederick, MD 21702 USA.
[Tan, Wei; Lou, Hong] NCI, Basic Sci Program, SAIC Frederick, NIH, Frederick, MD 21702 USA.
[Wells, David W.] NCI, Genet Core, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
[Bravo, Hector C.] Univ Maryland, Dept Comp Sci, Ctr Bioinformat & Computat Biol, College Pk, MD 20742 USA.
[Fredrikson, Karin M.; Harkins, Timothy T.] Roche Diagnost Corp, Indianapolis, IN USA.
[Milos, Patrice] Helicos BioSci Corp, Cambridge, MA USA.
[Linehan, W. Marston] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Yeager, Meredith] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Andresson, Thorkell] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick,NIH, Frederick, MD 21702 USA.
[Bova, G. Steven] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Bova, G. Steven] Univ Tampere, Inst Biomed Technol, FIN-33101 Tampere, Finland.
RP Nickerson, ML (reprint author), NCI, Canc & Inflammat Program, Bldg 560,Room 21-21, Frederick, MD 21702 USA.
EM nickersonml@mail.nih.gov; deanm@mail.nih.gov
RI Dean, Michael/G-8172-2012;
OI Dean, Michael/0000-0003-2234-0631; Corrada Bravo,
Hector/0000-0002-1255-4444
FU NIH; National Cancer Institute Center for Cancer Research; National
Institutes of Health [CA92234, HHSN26120080001E]; American Cancer
Society; Association for the Cure of Cancer of the Prostate
FX Contract grant sponsors: NIH; The National Cancer Institute Center for
Cancer Research; National Institutes of Health funding (CA92234,
HHSN26120080001E); John and Kathe Dyson; The American Cancer Society;
and the Association for the Cure of Cancer of the Prostate.
NR 68
TC 18
Z9 18
U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1059-7794
EI 1098-1004
J9 HUM MUTAT
JI Hum. Mutat.
PD SEP
PY 2013
VL 34
IS 9
BP 1231
EP 1241
DI 10.1002/humu.22346
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 200YZ
UT WOS:000323109200009
PM 23636849
ER
PT J
AU Johnston, JJ
Wen, KK
Keppler-Noreuil, K
McKane, M
Maiers, JL
Greiner, A
Sapp, JC
DeMali, KA
Rubenstein, PA
Biesecker, LG
AF Johnston, Jennifer J.
Wen, Kuo-Kuang
Keppler-Noreuil, Kim
McKane, Melissa
Maiers, Jessica L.
Greiner, Alexander
Sapp, Julie C.
DeMali, Kris A.
Rubenstein, Peter A.
Biesecker, Leslie G.
CA NIH Intramural Sequencing Ctr
TI Functional Analysis of a De Novo ACTB Mutation in a Patient with
Atypical Baraitser-Winter Syndrome
SO HUMAN MUTATION
LA English
DT Article
DE actin; ACTB; Dubowitz; Baraitser-Winter syndrome
AB Exome sequence analysis can be instrumental in identifying the genetic etiology behind atypical disease. We report a patient presenting with microcephaly, dysmorphic features, and intellectual disability with a tentative diagnosis of Dubowitz syndrome. Exome analysis was performed on the patient and both parents. A de novo missense variant was identified in ACTB, c.349G>A, p.E117K. Recent work in Baraitser-Winter syndrome has identified ACTB and ACTG1 mutations in a cohort of individuals, and we rediagnosed the patient with atypical Baraitser-Winter syndrome. We performed functional characterization of the variant actin and show that it alters cell adhesion and polymer formation supporting its role in disease. We present the clinical findings in the patient, comparison of this patient to other patients with ACTB/ACTG1 mutations, and results from actin functional studies that demonstrate novel functional attributes of this mutant protein. (C) 2013 Wiley Periodicals, Inc.
C1 [Johnston, Jennifer J.; Keppler-Noreuil, Kim; Sapp, Julie C.; Biesecker, Leslie G.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Wen, Kuo-Kuang; McKane, Melissa; Maiers, Jessica L.; Greiner, Alexander; DeMali, Kris A.; Rubenstein, Peter A.] Univ Iowa, Iowa City, IA USA.
[NIH Intramural Sequencing Ctr] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA.
RP Johnston, JJ (reprint author), NHGRI, Bldg 49,Room 4C64, Bethesda, MD 20892 USA.
EM jjohnsto@mail.nih.gov
FU National Institutes of Health [DC8803]; National Science Foundation
[1120478]
FX Contract grant sponsors: National Institutes of Health (#DC8803);
National Science Foundation (#1120478).
NR 35
TC 8
Z9 8
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1059-7794
J9 HUM MUTAT
JI Hum. Mutat.
PD SEP
PY 2013
VL 34
IS 9
BP 1242
EP 1249
DI 10.1002/humu.22350
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 200YZ
UT WOS:000323109200010
PM 23649928
ER
PT J
AU Tan, XH
Anzick, SL
Khan, SG
Ueda, T
Stone, G
DiGiovanna, JJ
Tamura, D
Wattendorf, D
Busch, D
Brewer, CC
Zalewski, C
Butman, JA
Griffith, AJ
Meltzer, PS
Kraemer, KH
AF Tan, Xiaohui
Anzick, Sarah L.
Khan, Sikandar G.
Ueda, Takahiro
Stone, Gary
DiGiovanna, John J.
Tamura, Deborah
Wattendorf, Daniel
Busch, David
Brewer, Carmen C.
Zalewski, Christopher
Butman, John A.
Griffith, Andrew J.
Meltzer, Paul S.
Kraemer, Kenneth H.
TI Chimeric Negative Regulation of p14ARF and TBX1 by a t(9;22)
Translocation Associated with Melanoma, Deafness, and DNA Repair
Deficiency
SO HUMAN MUTATION
LA English
DT Article
DE melanoma; TBX1; deafness; p14ARF; PATRR22; DiGeorge syndrome
AB Melanoma is the most deadly form of skin cancer and DiGeorge syndrome (DGS) is the most frequent interstitial deletion syndrome. We characterized a novel balanced t(9;22)(p21;q11.2) translocation in a patient with melanoma, DNA repair deficiency, and features of DGS including deafness and malformed inner ears. Using chromosome sorting, we located the 9p21 breakpoint in CDKN2A intron 1. This resulted in underexpression of the tumor suppressor p14 alternate reading frame (p14ARF); the reduced DNA repair was corrected by transfection with p14ARF. Ultraviolet radiation-type p14ARF mutations in his melanoma implicated p14ARF in its pathogenesis. The 22q11.2 breakpoint was located in a palindromic AT-rich repeat (PATRR22). We identified a new gene, FAM230A, that contains PATRR22 within an intron. The 22q11.2 breakpoint was located 800 kb centromeric to TBX1, which is required for inner ear development. TBX1 expression was greatly reduced. The translocation resulted in a chimeric transcript encoding portions of p14ARF and FAM230A. Inhibition of chimeric p14ARF-FAM230A expression increased p14ARF and TBX1 expression and improved DNA repair. Expression of the chimera in normal cells produced dominant negative inhibition of p14ARF. Similar chimeric mRNAs may mediate haploinsufficiency in DGS or dominant negative inhibition of other genes such as those involved in melanoma. Published 2013 Wiley Periodicals, Inc.
C1 [Tan, Xiaohui; Khan, Sikandar G.; Ueda, Takahiro; DiGiovanna, John J.; Tamura, Deborah; Kraemer, Kenneth H.] NCI, DNA Repair Sect, Dermatol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Anzick, Sarah L.; Stone, Gary; Meltzer, Paul S.] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Wattendorf, Daniel] Off Air Force Surgeon Gen, Washington, DC USA.
[Busch, David] Armed Forces Inst Pathol, Washington, DC 20306 USA.
[Brewer, Carmen C.; Zalewski, Christopher; Griffith, Andrew J.] Natl Inst Deafness & Commun Disorders, Otolaryngol Branch, Bethesda, MD USA.
[Butman, John A.] NIH, Radiol Branch, Ctr Clin, Bethesda, MD 20892 USA.
RP Kraemer, KH (reprint author), NCI, Dermatol Branch, Bldg 37 Room 4002, Bethesda, MD 20892 USA.
EM kraemerk@nih.gov
RI Butman, John/J-2780-2013
OI Butman, John/0000-0002-1547-9195
FU National Cancer Institute; National Institute of Deafness and
Communication Disorders; Clinical Center, National Institutes of Health,
Bethesda, Maryland
FX This work was supported by the Intramural Research Program of the
National Cancer Institute, the National Institute of Deafness and
Communication Disorders, and the Clinical Center, National Institutes of
Health, Bethesda, Maryland. We thank Drs. Paul Bergstresser and Clay
Cockerell for assistance in care of the patient, Drs. Vladimir Larionov,
Robert Walker, and Alexander Kovalchuk for assistance in molecular
analysis, Drs. Medha Bhagwhat and Paul Khavari for bioinformatics
advice, Dr. Doris Wu for expertise in mouse ear development, and Drs.
Kurt Kohn and Allan Balmian for metabolic pathway analysis.
NR 76
TC 6
Z9 6
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1059-7794
J9 HUM MUTAT
JI Hum. Mutat.
PD SEP
PY 2013
VL 34
IS 9
BP 1250
EP 1259
DI 10.1002/humu.22354
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 200YZ
UT WOS:000323109200011
PM 23661601
ER
PT J
AU Barnes, AM
Duncan, G
Weis, M
Paton, W
Cabral, WA
Mertz, EL
Makareeva, E
Gambello, MJ
Lacbawan, FL
Leikin, S
Fertala, A
Eyre, DR
Bale, SJ
Marini, JC
AF Barnes, Aileen M.
Duncan, Geraldine
Weis, MaryAnn
Paton, William
Cabral, Wayne A.
Mertz, Edward L.
Makareeva, Elena
Gambello, Michael J.
Lacbawan, Felicitas L.
Leikin, Sergey
Fertala, Andrzej
Eyre, David R.
Bale, Sherri J.
Marini, Joan C.
TI Kuskokwim Syndrome, a Recessive Congenital Contracture Disorder, Extends
the Phenotype of FKBP10 Mutations
SO HUMAN MUTATION
LA English
DT Article
DE osteogenesis imperfecta; contractures; FKBP65; FKBP10; Bruck syndrome;
cross-linking
AB Recessive mutations in FKBP10 at 17q21.2, encoding FKBP65, cause both osteogenesis imperfecta (OI) and Bruck syndrome (OI plus congenital contractures). Contractures are a variable manifestation of null/missense FKBP10 mutations. Kuskokwim syndrome (KS) is an autosomal recessive congenital contracture disorder found among Yup'ik Eskimos. Linkage mapping of KS to chromosome 17q21, together with contractures as a feature of FKBP10 mutations, made FKBP10 a candidate gene. We identified a homozygous three-nucleotide deletion in FKBP10 (c.877_879delTAC) in multiple Kuskokwim pedigrees; 3% of regional controls are carriers. The mutation deletes the highly conserved p.Tyr293 residue in FKBP65's third peptidyl-prolyl cis-trans isomerase domain. FKBP10 transcripts are normal, but mutant FKBP65 is destabilized to a residual 5%. Collagen synthesized by KS fibroblasts has substantially decreased hydroxylation of the telopeptide lysine crucial for collagen cross-linking, with 2%-10% hydroxylation in probands versus 60% in controls. Matrix deposited by KS fibroblasts has marked reduction in maturely cross-linked collagen. KS collagen is disorganized in matrix, and fibrils formed in vitro had subtle loosening of monomer packing. Our results imply that FKBP10 mutations affect collagen indirectly, by ablating FKBP65 support for collagen telopeptide hydroxylation by lysyl hydroxylase 2, thus decreasing collagen cross-links in tendon and bone matrix. FKBP10 mutations may also underlie other arthrogryposis syndromes. Published 2013. This article has been contributed to by US Government employees and their work is in the public domain in the USA.
C1 [Barnes, Aileen M.; Cabral, Wayne A.; Marini, Joan C.] NICHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD 20892 USA.
[Duncan, Geraldine; Bale, Sherri J.] NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA.
[Weis, MaryAnn; Eyre, David R.] Univ Washington, Orthopaed Res Labs, Seattle, WA 98195 USA.
[Paton, William] Alaska Native Med Ctr, Dept Orthopaed, Anchorage, AK USA.
[Mertz, Edward L.; Makareeva, Elena; Leikin, Sergey] NICHD, Sect Phys Biochem, NIH, Bethesda, MD 20892 USA.
[Fertala, Andrzej] Thomas Jefferson Univ, Dept Orthopaed Surg, Philadelphia, PA 19107 USA.
RP Marini, JC (reprint author), NICHD, Bone & Extracellular Matrix Branch, NIH, Bldg 10,Rm 10D39,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM oidoc@helix.nih.gov
RI Makareeva, Elena/F-5183-2011; Leikin, Sergey/A-5518-2008
OI Leikin, Sergey/0000-0001-7095-0739
FU NICHD; NIAMS; NIH [HD22657, AR37694, AR37318, AR061118, AR048544]
FX Contract grant sponsors: NICHD; NIAMS; NIH (HD22657, AR37694, AR37318,
AR061118, and AR048544).
NR 31
TC 16
Z9 16
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1059-7794
J9 HUM MUTAT
JI Hum. Mutat.
PD SEP
PY 2013
VL 34
IS 9
BP 1279
EP 1288
DI 10.1002/humu.22362
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 200YZ
UT WOS:000323109200014
PM 23712425
ER
PT J
AU Whelton, SP
Blankstein, R
Al-Mallah, MH
Lima, JAC
Bluemke, DA
Hundley, WG
Polak, JF
Blumenthal, RS
Nasir, K
Blaha, MJ
AF Whelton, Seamus P.
Blankstein, Ron
Al-Mallah, Mouaz H.
Lima, Joao A. C.
Bluemke, David A.
Hundley, W. Gregory
Polak, Joseph F.
Blumenthal, Roger S.
Nasir, Khurram
Blaha, Michael J.
TI Association of Resting Heart Rate With Carotid and Aortic Arterial
Stiffness: Multi-Ethnic Study of Atherosclerosis
SO HYPERTENSION
LA English
DT Article
DE cardiovascular diseases; heart rate; magnetic resonance imaging;
ultrasonography; vascular stiffness
ID SYMPATHETIC-NERVE ACTIVITY; MYOCARDIAL-INFARCTION; RISK-FACTOR;
CARDIOVASCULAR-DISEASE; ESSENTIAL-HYPERTENSION; INDEPENDENT PREDICTOR;
DISTENSIBILITY; HUMANS; MORTALITY; PRESSURE
AB Resting heart rate is an easily measured, noninvasive vital sign that is associated with cardiovascular disease events. The pathophysiology of this association is not known. We investigated the relationship between resting heart rate and stiffness of the carotid (a peripheral artery) and the aorta (a central artery) in an asymptomatic multi-ethnic population. Resting heart rate was recorded at baseline in the Multi-Ethnic Study of Atherosclerosis (MESA). Distensibility was used as a measure of arterial elasticity, with a lower distensibility indicating an increase in arterial stiffness. Carotid distensibility was measured in 6484 participants (98% of participants) using B-mode ultrasound, and aortic distensibility was measured in 3512 participants (53% of participants) using cardiac MRI. Heart rate was divided into quintiles and we used progressively adjusted models that included terms for physical activity and atrioventricular nodal blocking agents. Mean resting heart rate of participants (mean age, 62 years; 47% men) was 63 bpm (SD, 9.6 bpm). In unadjusted and fully adjusted models, carotid distensibility and aortic distensibility decreased monotonically with increasing resting heart rate (P for trend <0.001 and 0.009, respectively). The relationship was stronger for carotid versus aortic distensibility. Similar results were seen using the resting heart rate taken at the time of MRI scanning. Our results suggest that a higher resting heart rate is associated with an increased arterial stiffness independent of atrioventricular nodal blocker use and physical activity level, with a stronger association for a peripheral (carotid) compared with a central (aorta) artery.
C1 [Whelton, Seamus P.] Johns Hopkins Bloomberg Sch Publ Hlth, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
[Whelton, Seamus P.; Blumenthal, Roger S.; Nasir, Khurram; Blaha, Michael J.] Johns Hopkins Ciccarone Ctr Prevent Heart Dis, Baltimore, MD 21287 USA.
[Blankstein, Ron] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA.
[Blankstein, Ron] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Al-Mallah, Mouaz H.] Natl Guard Hlth Affairs, King Abdul Aziz Med City Riyadh, King Abdul Aziz Cardiac Ctr, Cardiac Imaging, Riyadh, Saudi Arabia.
[Lima, Joao A. C.; Blumenthal, Roger S.; Nasir, Khurram; Blaha, Michael J.] Johns Hopkins Sch Med, Div Cardiol, Baltimore, MD USA.
[Bluemke, David A.] Ctr Clin, Bethesda, MD USA.
[Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA.
[Hundley, W. Gregory] Wake Forest Univ, Dept Internal Med Cardiol, Winston Salem, NC 27109 USA.
[Polak, Joseph F.] Tufts Univ, Sch Med, Dept Radiol, Tufts Med Ctr, Boston, MA 02111 USA.
[Nasir, Khurram] Baptist Hlth South Florida, Ctr Prevent & Wellness, Miami, FL USA.
[Nasir, Khurram] Florida Int Univ, Herbert Wertheim Coll Med, Dept Med, Miami, FL 33199 USA.
[Nasir, Khurram] Florida Int Univ, Dept Epidemiol, Robert Stempel Coll Publ Hlth, Miami, FL 33199 USA.
RP Blaha, MJ (reprint author), Johns Hopkins Ciccarone Ctr Prevent Heart Dis, Johns Hopkins Sch Med, Div Cardiol, 1830 E Monument St,Carnegie 565A, Baltimore, MD 21287 USA.
EM mblaha1@jhmi.edu
OI Bluemke, David/0000-0002-8323-8086; Al-Mallah, Mouaz/0000-0003-2348-0484
FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95169];
NCRR [UL1-RR-024156, UL1-RR-025005]
FX This research was supported by contracts N01-HC-95159 through
N01-HC-95169 from the National Heart, Lung, and Blood Institute and by
grants UL1-RR-024156 and UL1-RR-025005 from NCRR.
NR 51
TC 27
Z9 30
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD SEP
PY 2013
VL 62
IS 3
BP 477
EP 484
DI 10.1161/HYPERTENSIONAHA.113.01605
PG 8
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 201OA
UT WOS:000323149700017
PM 23836802
ER
PT J
AU Cheng, S
Gupta, DK
Claggett, B
Sharrett, AR
Shah, AM
Skali, H
Takeuchi, M
Ni, HY
Solomon, SD
AF Cheng, Susan
Gupta, Deepak K.
Claggett, Brian
Sharrett, A. Richey
Shah, Amil M.
Skali, Hicham
Takeuchi, Madoka
Ni, Hanyu
Solomon, Scott D.
TI Differential Influence of Distinct Components of Increased Blood
Pressure on Cardiovascular Outcomes: From the Atherosclerosis Risk in
Communities Study
SO HYPERTENSION
LA English
DT Article
DE blood pressure; cardiovascular diseases; epidemiology; hypertension;
outcomes assessment
ID CORONARY-ARTERY-DISEASE; PULSE-WAVE VELOCITY; AGE-RELATED-CHANGES;
MYOCARDIAL-INFARCTION; HEART-FAILURE; HYPERTENSIVE PATIENTS;
MORTALITY-RATES; SEX-DIFFERENCES; UNITED-STATES; ALL-CAUSE
AB Elevation in blood pressure (BP) increases risk for all cardiovascular events. Nevertheless, the extent to which different indices of BP elevation may be associated to varying degrees with different cardiovascular outcomes remains unclear. We studied 13340 participants (aged 54 +/- 6 years, 56% women and 27% black) of the Atherosclerosis Risk in Communities Study who were free of baseline cardiovascular disease. We used Cox proportional hazards models to compare the relative contributions of systolic BP, diastolic BP, pulse pressure, and mean arterial pressure to risk for coronary heart disease, heart failure, stroke, and all-cause mortality. For each multivariable-adjusted model, the largest area under the receiver-operating curve (AUC) and smallest -2 log-likelihood values were used to identify BP measures with the greatest contribution to risk prediction for each outcome. A total of 2095 coronary heart disease events, 1669 heart failure events, 771 stroke events, and 3016 deaths occurred during 18 +/- 5 years of follow-up. In multivariable analyses adjusting for traditional cardiovascular risk factors, the BP measures with the greatest risk contributions were the following: systolic BP for coronary heart disease (AUC=0.74); pulse pressure for heart failure (AUC=0.79); systolic BP for stroke (AUC=0.74); and pulse pressure for all-cause mortality (AUC=0.74). With few exceptions, results were similar in analyses stratified by age, sex, and race. Our data indicate that distinct BP components contribute variably to risk for different cardiovascular outcomes.
C1 [Cheng, Susan; Gupta, Deepak K.; Claggett, Brian; Shah, Amil M.; Skali, Hicham; Takeuchi, Madoka; Solomon, Scott D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA.
[Sharrett, A. Richey] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Ni, Hanyu] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Cheng, S (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA.
EM scheng3@partners.org
OI Skali, Hicham/0000-0002-5629-4138
FU National Heart, Lung, and Blood Institute [HHSN268201100005C,
HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN2682011000
09C, HHSN268201100010C, HHSN268201100011C, HHSN268 201100012C]; Ellison
Foundation; [K99-HL-107642]
FX The Atherosclerosis Risk in Communities (ARIC) Study is a collaborative
study supported by the following National Heart, Lung, and Blood
Institute contracts: HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN2682011000 09C,
HHSN268201100010C, HHSN268201100011C, and HHSN268 201100012C. Dr Cheng
is supported in part by K99-HL-107642 and a grant from the Ellison
Foundation.
NR 43
TC 8
Z9 8
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD SEP
PY 2013
VL 62
IS 3
BP 492
EP 498
DI 10.1161/HYPERTENSIONAHA.113.01561
PG 7
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 201OA
UT WOS:000323149700019
PM 23876475
ER
PT J
AU Goldenberg, RL
McClure, EM
Kodkany, B
Wembodinga, G
Pasha, O
Esamai, F
Tshefu, A
Patel, A
Mabaye, H
Goudar, S
Saleem, S
Waikar, M
Langer, A
Bose, CL
Rubens, CE
Wright, LL
Moore, J
Blanc, A
AF Goldenberg, Robert L.
McClure, Elizabeth M.
Kodkany, Bhala
Wembodinga, Gilbert
Pasha, Omrana
Esamai, Fabian
Tshefu, Antoinette
Patel, Archana
Mabaye, Hillary
Goudar, Shivaparasad
Saleem, Sarah
Waikar, Manjushri
Langer, Ana
Bose, Carl L.
Rubens, Craig E.
Wright, Linda L.
Moore, Janet
Blanc, Ann
TI A multi-country study of the "intrapartum stillbirth and early neonatal
death indicator" in hospitals in low-resource settings
SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS
LA English
DT Article
DE Doptone; Fetal heart tones; Hospital-based perinatal mortality; Neonatal
mortality; Perinatal mortality; Stillbirth
ID NEWBORN; BIRTHS
AB Objective: To determine the feasibility of introducing a simple indicator of quality of obstetric and neonatal care and to determine the proportion of potentially avoidable perinatal deaths in hospitals in low-income countries. Methods: Between September 1, 2011, and February 29, 2012, data were collected from consecutive women who were admitted to the labor ward of 1 of 6 hospitals in 4 low-income countries. Fetal heart tones on admission were monitored, and demographic and birth data were recorded. Results: Data were obtained for 3555 women and 3593 neonates (including twins). The doptone was used on 97% of women admitted. The overall perinatal mortality rate was 34 deaths per 1000 deliveries. Of the perinatal deaths, 40%-45% occurred in the hospital and were potentially preventable by better hospital care. Conclusion: The results demonstrated that it is possible to accurately determine fetal viability on admission via a doptone. Implementation of doptone use, coupled with a concise data record, might form the basis of a low-cost and sustainable program to monitor and evaluate efforts to improve quality of care and ultimately might help to reduce the in-hospital component of perinatal mortality in low-income countries. (C) 2013 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
C1 [Goldenberg, Robert L.] Columbia Univ, Dept Obstet & Gynecol, New York, NY 10032 USA.
[McClure, Elizabeth M.; Moore, Janet] Res Triangle Inst, Dept Social Stat & Environm Sci, Durham, NC USA.
[Kodkany, Bhala; Goudar, Shivaparasad] Jawaharlal Nehru Med Coll, Karnataka Lingayat Educ Soc, Dept Obstet, Belgaum, India.
[Wembodinga, Gilbert; Tshefu, Antoinette] Sch Publ Hlth, Kinshasa, Zaire.
[Pasha, Omrana; Saleem, Sarah] Aga Khan Univ, Dept Community Hlth Sci, Karachi, Pakistan.
[Esamai, Fabian; Mabaye, Hillary] Moi Univ, Dept Pediat, Eldoret, Kenya.
[Patel, Archana; Waikar, Manjushri] Lata Med Res Fdn, Nagpur, Maharashtra, India.
[Langer, Ana] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA.
[Bose, Carl L.] Univ N Carolina, Dept Pediat, Chapel Hill, NC USA.
[Rubens, Craig E.] Seattle Childrens Hosp, Global Alliance Prevent Preterm Birth & Stillbirt, Seattle, WA USA.
[Wright, Linda L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Goldenberg, RL (reprint author), Columbia Univ, Coll Med, Dept Obstet & Gynecol, New York, NY 10032 USA.
EM rlg88@columbia.edu
OI GOUDAR, SHIVAPRASAD/0000-0002-8680-7053
FU Bill & Melinda Gates Foundation; Eunice Kennedy Shriver NICHD Global
Network for Women's and Children's Health Research grants [U01 HD042372,
U01 HD040607, U01 HD040636, U01 HD058322, U01 HD058326]
FX Support for the study design meeting and study were provided by the Bill
& Melinda Gates Foundation-funded Maternal Health Task Force at
EngenderHealth, GAPPS and by the Eunice Kennedy Shriver NICHD Global
Network for Women's and Children's Health Research grants (U01 HD042372,
U01 HD040607, U01 HD040636, U01 HD058322, U01 HD058326). GAPPS (C.E.R.),
MHTF (A.L., A.B.), and NICHD (L.L.W.) contributed to development of the
study protocol and review of the manuscript.
NR 10
TC 12
Z9 12
U1 0
U2 5
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0020-7292
J9 INT J GYNECOL OBSTET
JI Int. J. Gynecol. Obstet.
PD SEP
PY 2013
VL 122
IS 3
BP 230
EP 233
DI 10.1016/j.ijgo.2013.04.008
PG 4
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 204XS
UT WOS:000323405200012
PM 23796259
ER
PT J
AU Preuss, N
Salehi, B
van der Veen, JW
Shen, J
Drevets, WC
Hodgkinson, C
Goldman, D
Hasler, G
AF Preuss, Nora
Salehi, Basira
van der Veen, Jan Willem
Shen, Jun
Drevets, Wayne C.
Hodgkinson, Colin
Goldman, David
Hasler, Gregor
TI Associations between prefrontal gamma-aminobutyric acid concentration
and the tryptophan hydroxylase isoform 2 gene, a panic disorder risk
allele in women
SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE GABA; genetics; magnetic resonance spectroscopy; single nucleotide
polymorphisms; tryptophan hydroxylase 2
ID MAGNETIC-RESONANCE SPECTROSCOPY; MAJOR DEPRESSION;
TRYPTOPHAN-HYDROXYLASE-2 GENE; TRANSMISSION DISEQUILIBRIUM; POLYMORPHIC
VARIANTS; GABA CONCENTRATIONS; BIPOLAR DISORDER; SEX-DIFFERENCES; TPH2
GENE; IN-VIVO
AB Associations between the central serotonergic and gamma-aminobutyric acid (GABA) systems play key roles in the prefrontal cortical regulation of emotion and cognition and in the pathophysiology and pharmacotherapy of highly prevalent psychiatric disorders. The goal of this study was to test the effects of common variants of the tryptophan hydroxylase isoform 2 (TPH2) gene on GABA concentration in the prefrontal cortex (PFC) using magnetic resonance spectroscopy. In this study involving 64 individuals, we examined the associations between prefrontal cortical GABA concentration and 12 single nucleotide polymorphisms (SNPs) spanning the TPH2 gene, including rs4570625 (-703 G/T SNP), a potentially functional TPH2 polymorphism that has been associated with decreased TPH2 mRNA expression and panic disorder. Our results revealed a significant association between increased GABA concentration in the PFC and the T-allele frequencies of two TPH2 SNPs, namely rs4570625 (-703 G/T) and rs2129575 (p <= 0.0004) and the C-allele frequency of one TPH2 SNP, namely rs1386491 (p=0.0003) in female subjects. We concluded that rs4570625 (-703 G/T), rs2129575 and rs1386491 play a significant role in GABAergic neurotransmission and may contribute to the sex-specific dysfunction of the GABAergic system in the PFC.
C1 [Preuss, Nora] Univ Bern, Dept Psychol, CH-3012 Bern, Switzerland.
[Salehi, Basira; Hasler, Gregor] Univ Bern, Psychiat Univ Hosp, CH-3012 Bern, Switzerland.
[van der Veen, Jan Willem] NIMH, Magnet Resonance Spect Core, Bethesda, MD 20892 USA.
[Shen, Jun] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA.
[Drevets, Wayne C.] Laureate Inst Brain Res, Tulsa, OK USA.
[Drevets, Wayne C.] Univ Oklahoma, Coll Med, Tulsa, OK USA.
[Drevets, Wayne C.] Johnson & Johnson Inc, Janssen Res & Dev LLC, Titusville, NJ USA.
[Hodgkinson, Colin; Goldman, David] NIAAA, Neurogenet Lab, Bethesda, MD USA.
RP Hasler, G (reprint author), Psychiat Univ Hosp, Bolligenstr 111, CH-3000 Bern 60, Switzerland.
EM g.hasler@bluewin.ch
RI Hasler, Gregor/E-4845-2012; Goldman, David/F-9772-2010
OI Hasler, Gregor/0000-0002-8311-0138; Goldman, David/0000-0002-1724-5405
FU Intramural Research Program of the National Institutes of Mental Health;
Lundebck; Servier; Lilly; Bistol-Myers Squibb; GlaxoSmithKline; Astra
Zeneca
FX This research was supported by the Intramural Research Program of the
National Institutes of Mental Health. We thank Qiaoping Yuan and
Pei-Hong Shen for their support in data management and bioinformatics.
Gregor Hasler received honoraria or consulting fees from Lundebck,
Servier, Lilly, Bistol-Myers Squibb, GlaxoSmithKline and Astra Zeneca
for projects unrelated to this study. Wayne Drevets, M. D. is an
employee of Johnson & Johnson, Inc. and has consulted for Myriad/Rules
Based Medicine and Eisai, Inc. for projects unrelated to this study.
NR 62
TC 4
Z9 4
U1 1
U2 14
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1461-1457
J9 INT J NEUROPSYCHOPH
JI Int. J. Neuropsychopharmacol.
PD SEP
PY 2013
VL 16
IS 8
BP 1707
EP 1717
DI 10.1017/S1461145713000254
PG 11
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 201TQ
UT WOS:000323166300002
PM 23552096
ER
PT J
AU Cheung, WY
Aziz, N
Noone, AM
Rowland, JH
Potosky, AL
Ayanian, JZ
Virgo, KS
Ganz, PA
Stefanek, M
Earle, CC
AF Cheung, Winson Y.
Aziz, Noreen
Noone, Anne-Michelle
Rowland, Julia H.
Potosky, Arnold L.
Ayanian, John Z.
Virgo, Katherine S.
Ganz, Patricia A.
Stefanek, Michael
Earle, Craig C.
TI Physician preferences and attitudes regarding different models of cancer
survivorship care: a comparison of primary care providers and
oncologists
SO JOURNAL OF CANCER SURVIVORSHIP
LA English
DT Article
DE Cancer; Survivorship; Care models; Physician; Preferences
ID FOLLOW-UP; BREAST-CANCER; COLORECTAL-CANCER; PREVENTIVE CARE; SPECIALTY
CARE; DIAGNOSIS; INTERFACE; TRENDS; VIEWS
AB New strategies for delivering cancer follow-up care are needed. We surveyed primary care providers (PCPs) and oncologists to assess how physician attitudes toward and self-efficacy with cancer follow-up affect preferences for different cancer survivorship models.
The survey of physician attitudes regarding the care of cancer survivors was mailed to a randomly selected national sample of PCPs and oncologists to evaluate their perspectives regarding physician roles, knowledge about survivorship care processes, and views on cancer surveillance. Multinomial logistic regression models were constructed to examine how physician attitudes towards, and self-efficacy with, their own skills affected preferences for different cancer survivorship care models.
Of 3,434 physicians identified, a total of 2,026 participants provided eligible responses: 938 PCPs and 1,088 oncologists. Most PCPs (51 %) supported a PCP/shared care model; whereas, the majority of specialists (59 %) strongly endorsed an oncologist-based model (p < 0.001). Less than a quarter of PCPs and oncologists preferred specialized survivor clinics. A significant proportion of oncologists (87 %) did not feel that PCPs should take on the primary role of cancer follow-up. Most PCPs believed that they were better able to perform breast and colorectal cancer follow-up (57 %), detect recurrent cancers (74 %), and offer psychosocial support (50 %), but only a minority (32 %) was willing to assume primary responsibility. PCPs already involved with cancer surveillance (43 %) were more likely to prefer a PCP/shared care than oncologist-based survivorship model (OR, 2.08; 95 % CI, 1.34-3.23).
PCPs and oncologists have different preferences for models of cancer survivorship care. Prior involvement with cancer surveillance was one of the strongest predictors of PCPs' willingness to assume this responsibility.
C1 [Cheung, Winson Y.] British Columbia Canc Agcy, Div Med Oncol, Vancouver, BC V5Z 4E6, Canada.
[Aziz, Noreen] NINR, Off Extramural Programs, Div Extramural Act, NIH, Bethesda, MD 20892 USA.
[Noone, Anne-Michelle] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Rowland, Julia H.] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Potosky, Arnold L.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.
[Ayanian, John Z.] Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA.
[Ayanian, John Z.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Virgo, Katherine S.] Amer Canc Soc, Hlth Serv Res Program, Intramural Res Dept, Atlanta, GA 30329 USA.
[Virgo, Katherine S.; Stefanek, Michael] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Med, Div Canc Prevent & Control Res, Los Angeles, CA 90024 USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Publ Hlth, Div Canc Prevent & Control Res, Los Angeles, CA 90024 USA.
[Earle, Craig C.] Ontario Inst Canc Res, Toronto, ON, Canada.
[Earle, Craig C.] Inst Clin Evaluat Sci, Toronto, ON M4N 3M5, Canada.
RP Earle, CC (reprint author), Inst Clin Evaluat Sci, 2075 Bayview Ave,G Wing 106, Toronto, ON M4N 3M5, Canada.
EM craig.earle@ices.on.ca
RI chen, zhu/K-5923-2013
FU National Cancer Institute [HHSN261201000316C]
FX National Cancer Institute HHSN261201000316C and intramural support from
the American Cancer Society
NR 34
TC 25
Z9 25
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1932-2259
J9 J CANCER SURVIV
JI J. Cancer Surviv.-Res. Pract.
PD SEP
PY 2013
VL 7
IS 3
BP 343
EP 354
DI 10.1007/s11764-013-0281-y
PG 12
WC Oncology; Social Sciences, Biomedical
SC Oncology; Biomedical Social Sciences
GA 197WM
UT WOS:000322883100007
PM 23526165
ER
PT J
AU Stanton, AL
Morra, ME
Diefenbach, MA
Miller, SM
Perocchia, RS
Raich, PC
Fleisher, L
Wen, KY
Tran, ZV
Mohamed, NE
George, R
Bright, MA
Marcus, AC
AF Stanton, Annette L.
Morra, Marion E.
Diefenbach, Michael A.
Miller, Suzanne M.
Perocchia, Rosemarie Slevin
Raich, Peter C.
Fleisher, Linda
Wen, Kuang-Yi
Zung Vu Tran
Mohamed, Nihal E.
George, Roshini
Bright, Mary Anne
Marcus, Alfred C.
TI Responding to a significant recruitment challenge within three
nationwide psychoeducational trials for cancer patients
SO JOURNAL OF CANCER SURVIVORSHIP
LA English
DT Article
DE Cancer; Accrual; Recruitment; Randomized controlled trial;
Psychoeducational; Survivorship
ID RANDOMIZED CONTROLLED-TRIAL; SPANISH-SPEAKING SMOKERS; STAGE
BREAST-CANCER; INFORMATION-SERVICE; MINORITY WOMEN; STRATEGIES;
RETENTION; INTERVENTION; PREVENTION; SURVIVORS
AB When faced with a significant recruitment challenge for three nationwide psychoeducational trials targeting prostate and breast cancer patients, the Cancer Information Service Research Consortium initiated outreach efforts to increase accrual. Recruitment is reported by major outreach strategy to inform the use of similar campaigns, either as primary recruitment efforts or to supplement "in-reach" recruitment within oncology settings.
During a 33-month period, recruitment was tracked from the National Cancer Institute's Cancer Information Service (CIS), the American Cancer Society (ACS), Dr. Susan Love Research Foundation's Love/Avon Army of Women (AOW), Internet advertising, press releases, radio/television interviews, recruitment materials in community venues, and outreach to churches and cancer support organizations.
Across projects, the majority (89 %) of recruited participants (N = 2,134) was obtained from the CIS (n = 901, 19 months of recruitment), AOW (n = 869, 18 months), and ACS (n = 123, 12 months). Other efforts showed minimal gain in recruitment.
Cancer information programs (e.g., CIS and ACS) and registries of individuals willing to participate in cancer-related research (e.g., AOW) can represent exceptional resources for outreach recruitment of cancer patients, especially when the eligibility criteria are highly restrictive. However, these resources do not yield samples representative of the larger population of adults diagnosed with cancer, and conclusions from such trials must be tempered accordingly.
Inadequate recruitment to randomized controlled trials limits the creation of useful interventions for cancer survivors. By enrolling in cancer registries and taking part in research, cancer survivors can contribute to the development of effective resources for the survivor population.
C1 [Stanton, Annette L.] Univ Calif Los Angeles, Johnsson Comprehens Canc Ctr, Dept Psychol, Los Angeles, CA 90095 USA.
[Stanton, Annette L.] Univ Calif Los Angeles, Johnsson Comprehens Canc Ctr, Dept Psychiat Biobehav Sci, Los Angeles, CA 90095 USA.
[Morra, Marion E.] Morra Commun, Milford, CT USA.
[Miller, Suzanne M.; Fleisher, Linda; Wen, Kuang-Yi] Fox Chase Temple Hlth, Philadelphia, PA USA.
[Mohamed, Nihal E.; Bright, Mary Anne] Icahn Sch Med Mt Sinai, New York, NY USA.
[Perocchia, Rosemarie Slevin] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Raich, Peter C.] Denver Hlth & Hosp Author, Denver, CO USA.
[Zung Vu Tran; Marcus, Alfred C.] Univ Colorado, Ctr Canc, Denver, CO 80262 USA.
[George, Roshini] Amer Canc Soc, Atlanta, GA 30329 USA.
[Bright, Mary Anne] NCI, Off Publ Informat & Resource Management, Off Commun & Educ, Bethesda, MD 20892 USA.
RP Stanton, AL (reprint author), Univ Calif Los Angeles, Johnsson Comprehens Canc Ctr, Dept Psychol, 1285 Franz Hall,Box 951563, Los Angeles, CA 90095 USA.
EM astanton@ucla.edu
OI Tran, Zung/0000-0002-9322-9562
FU NCI of the National Institutes of Health [5P01CA057586]
FX This research was supported by grant 5P01CA057586 from the NCI of the
National Institutes of Health.
NR 41
TC 2
Z9 2
U1 0
U2 10
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1932-2259
J9 J CANCER SURVIV
JI J. Cancer Surviv.-Res. Pract.
PD SEP
PY 2013
VL 7
IS 3
BP 392
EP 403
DI 10.1007/s11764-013-0282-x
PG 12
WC Oncology; Social Sciences, Biomedical
SC Oncology; Biomedical Social Sciences
GA 197WM
UT WOS:000322883100011
PM 23595235
ER
PT J
AU Jena, AB
Prasad, V
AF Jena, Anupam B.
Prasad, Vinay
TI Duty Hour Reform in a Shifting Medical Landscape
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
ID MYOCARDIAL-INFARCTION; PATIENT SAFETY; RESIDENT; SUPERVISION; EMERGENCY;
WORK; MORTALITY; EDUCATION; ERROR; CARE
AB The circumstances that led to the death of Libby Zion in 1984 prompted national discussions about the impact of resident fatigue on patient outcomes. Nearly 30 years later, national duty hour reforms largely motivated by patient safety concerns have demonstrated a negligible impact of duty hour reductions on patient mortality. We suggest that the lack of an impact of duty hour reforms on patient mortality is due to a different medical landscape today than existed in 1984. Improvements in quality of care made possible by computerized order entry, automated medication checks, inpatient pharmacists, and increased resident supervision have, among other systemic changes, diminished the adverse impact that resident fatigue is able to have on patient outcomes. Given this new medical landscape, advocacy towards current and future duty hour reforms may be best justified by evidence of the impact of duty hour reform on resident wellbeing, education, and burnout.
C1 [Jena, Anupam B.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Jena, Anupam B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Jena, Anupam B.] Natl Bur Econ Res, Cambridge, MA 02138 USA.
[Prasad, Vinay] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Jena, AB (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA.
EM jena@hcp.med.harvard.edu; vinayak.prasad@nih.gov
NR 23
TC 2
Z9 2
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD SEP
PY 2013
VL 28
IS 9
BP 1238
EP 1240
DI 10.1007/s11606-013-2439-8
PG 3
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 202XR
UT WOS:000323254700028
PM 23568191
ER
PT J
AU Leclezio, L
Jansen, AC
Whittemore, VH
Whilmshurst, J
Schlegel, B
de Vries, PJ
AF Leclezio, L.
Jansen, A. C.
Whittemore, V. H.
Whilmshurst, J.
Schlegel, B.
de Vries, P. J.
TI THE TUBEROUS SCLEROSIS COMPLEX ASSOCIATED NEUROPSYCHIATRIC DISORDERS
(TAND) CHECKLIST - PILOT VALIDATION OF A NEW SCREENING TOOL FOR
NEUROPSYCHIATRIC MANIFESTATIONS IN TSC
SO JOURNAL OF INTELLECTUAL DISABILITY RESEARCH
LA English
DT Meeting Abstract
DE TSC; TAND
C1 [Leclezio, L.; de Vries, P. J.] Univ Cape Town, Div Child & Adolescent Psychiat, ZA-7700 Rondebosch, South Africa.
[Jansen, A. C.] Vrije Univ Brussel, Pediat Neurol Unit, UZ Brussel, Brussels, Belgium.
[Whittemore, V. H.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA.
[Whilmshurst, J.; Schlegel, B.] Univ Cape Town, Dept Paediat Neurol, Red Cross War Mem Childrens Hosp, ZA-7700 Rondebosch, South Africa.
RI Jansen, Anna/P-3121-2014
OI Jansen, Anna/0000-0002-3835-2824
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 0964-2633
J9 J INTELL DISABIL RES
JI J. Intell. Disabil. Res.
PD SEP
PY 2013
VL 57
IS 9
BP 800
EP 800
PG 1
WC Education, Special; Genetics & Heredity; Clinical Neurology; Psychiatry;
Rehabilitation
SC Education & Educational Research; Genetics & Heredity; Neurosciences &
Neurology; Psychiatry; Rehabilitation
GA 201DS
UT WOS:000323121500021
ER
PT J
AU Yaniv, Y
Sirenko, S
Ziman, BD
Spurgeon, HA
Maltsev, VA
Lakatta, EG
AF Yaniv, Yael
Sirenko, Syevda
Ziman, Bruce D.
Spurgeon, Harold A.
Maltsev, Victor A.
Lakatta, Edward G.
TI New evidence for coupled clock regulation of the normal automaticity of
sinoatrial nodal pacemaker cells: Bradycardic effects of ivabradine are
linked to suppression of intracellular Ca2+ cycling
SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
LA English
DT Article
DE Sinoatrial nodal pacemaker cells; Ca2+ cycling; Ion channels;
Physiology; Sarcoplasmic reticulum
ID HEART-RATE REDUCTION; RYANODINE RECEPTOR; CARDIAC PREPARATIONS; RABBIT;
PHOSPHORYLATION; SIZE; DEPOLARIZATION; MECHANISM; CHANNELS; SYSTEM
AB Beneficial clinical bradycardic effects of ivabradine (IVA) have been interpreted solely on the basis of If inhibition, because IVA specifically inhibits I-f in sinoatrial nodal pacemaker cells (SANC). However, it has been recently hypothesized that SANC normal automaticity is regulated by crosstalk between an "M clock," the ensemble of surface membrane ion channels, and a "Ca2+ clock," the sarcoplasmic reticulum (SR). We tested the hypothesis that crosstalk between the two clocks regulates SANC automaticity, and that indirect suppression of the Ca2+ clock further contributes to IVA-induced bradycardia. IVA (3 mu M) not only reduced If amplitude by 45 +/- 6% in isolated rabbit SANC, but the IVA-induced slowing of the action potential (AP) firing rate was accompanied by reduced SR Ca2+ load, slowed intracellular Ca2+ cycling kinetics, and prolonged the period of spontaneous local Ca2+ releases (LCRs) occurring during diastolic depolarization. Direct and specific inhibition of SERCA2 by cyclopiazonic acid (CPA) had effects similar to IVA on LCR period and AP cycle length. Specifically, the LCR period and AP cycle length shift toward longer times almost equally by either direct perturbations of the M clock (IVA) or the Ca2+ clock (CPA), indicating that the LCR period reports the crosstalk between the clocks. Our numerical model simulations predict that entrainment between the two clocks that involves a reduction in I-NCX( during diastolic depolarization is required to explain the experimentally AP firing rate reduction by IVA. In summary, our study provides new evidence that a coupled-clock system regulates normal cardiac pacemaker cell automaticity. Thus, IVA-induced bradycardia includes a suppression of both clocks within this system. Published by Elsevier Ltd.
C1 [Yaniv, Yael; Sirenko, Syevda; Ziman, Bruce D.; Spurgeon, Harold A.; Maltsev, Victor A.; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Lakatta, EG (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Intramural Res Program,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM LakattaE@mail.nih.gov
RI Yaniv, Yael/B-3311-2015
OI Yaniv, Yael/0000-0002-5183-6284
FU Intramural Research Program of the National Institute on Aging, National
Institutes of Health
FX The work was supported entirely by the Intramural Research Program of
the National Institute on Aging, National Institutes of Health.
NR 27
TC 22
Z9 22
U1 0
U2 16
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2828
EI 1095-8584
J9 J MOL CELL CARDIOL
JI J. Mol. Cell. Cardiol.
PD SEP
PY 2013
VL 62
BP 80
EP 89
DI 10.1016/j.yjmcc.2013.04.026
PG 10
WC Cardiac & Cardiovascular Systems; Cell Biology
SC Cardiovascular System & Cardiology; Cell Biology
GA 198RV
UT WOS:000322940900011
PM 23651631
ER
PT J
AU Goldstein, DS
Sullivan, P
Holmes, C
Miller, GW
Alter, S
Strong, R
Mash, DC
Kopin, IJ
Sharabi, Y
AF Goldstein, David S.
Sullivan, Patti
Holmes, Courtney
Miller, Gary W.
Alter, Shawn
Strong, Randy
Mash, Deborah C.
Kopin, Irwin J.
Sharabi, Yehonatan
TI Determinants of buildup of the toxic dopamine metabolite DOPAL in
Parkinson's disease
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE DOPAC; DOPAL; dopamine; DOPET; monoamine oxidase; Parkinson's disease
ID REDUCED VESICULAR STORAGE; ALPHA-SYNUCLEIN; SUBSTANTIA-NIGRA; IN-VIVO;
NEURODEGENERATIVE DISEASES; ALDEHYDE DEHYDROGENASE; KNOCKOUT MICE; HUMAN
BRAIN; PC12 CELLS; 3,4-DIHYDROXYPHENYLACETALDEHYDE
AB Intra-neuronal metabolism of dopamine (DA) begins with production of 3,4-dihydroxyphenylacetaldehyde (DOPAL), which is toxic. According to the catecholaldehyde hypothesis,' DOPAL destroys nigrostriatal DA terminals and contributes to the profound putamen DA deficiency that characterizes Parkinson's disease (PD). We tested the feasibility of using post-mortem patterns of putamen tissue catechols to examine contributions of altered activities of the type 2 vesicular monoamine transporter (VMAT2) and aldehyde dehydrogenase (ALDH) to the increased DOPAL levels found in PD. Theoretically, the DA:DOPA concentration ratio indicates vesicular uptake, and the 3,4-dihydroxyphenylacetic acid:DOPAL ratio indicates ALDH activity. We validated these indices in transgenic mice with very low vesicular uptake (VMAT2-Lo) or with knockouts of the genes encoding ALDH1A1 and ALDH2 (ALDH1A1,2 KO), applied these indices in PD putamen, and estimated the percent decreases in vesicular uptake and ALDH activity in PD. VMAT2-Lo mice had markedly decreased DA:DOPA (50 vs. 1377, p<0.0001), and ALDH1A1,2 KO mice had decreased 3,4-dihydroxyphenylacetic acid:DOPAL (1.0 vs. 11.2, p<0.0001). In PD putamen, vesicular uptake was estimated to be decreased by 89% and ALDH activity by 70%. Elevated DOPAL levels in PD putamen reflect a combination of decreased vesicular uptake of cytosolic DA and decreased DOPAL detoxification by ALDH.
C1 [Goldstein, David S.; Sullivan, Patti; Holmes, Courtney; Kopin, Irwin J.; Sharabi, Yehonatan] NINDS, Clin Neurocardiol Sect, Clin Neurosci Program, Div Intramural Res,NIH, Bethesda, MD 20892 USA.
[Miller, Gary W.; Alter, Shawn] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
[Strong, Randy] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA.
[Strong, Randy] South Texas Vet Hlth Care Network, San Antonio, TX USA.
[Mash, Deborah C.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Sharabi, Yehonatan] Tel Aviv Univ, Sackler Fac Med, IL-52621 Tel Hashomer, Israel.
RP Goldstein, DS (reprint author), 9000 Rockville Pike,Bldg 10 Rm 5N220, Bethesda, MD 20892 USA.
EM goldsteind@ninds.nih.gov
OI Miller, Gary/0000-0001-8984-1284
FU National Institute of Neurological Disorders and Stroke
FX The research reported here was supported by the intramural research
program of the National Institute of Neurological Disorders and Stroke.
We thank Margaret Basile and Margaret Wey for numerous tissue samples,
neurochemical data from which were important for the present report. The
Authors have no conflicts of interest to disclose.
NR 52
TC 39
Z9 39
U1 1
U2 17
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD SEP
PY 2013
VL 126
IS 5
BP 591
EP 603
DI 10.1111/jnc.12345
PG 13
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 204TV
UT WOS:000323393400005
PM 23786406
ER
PT J
AU Gulvady, AA
Ciolino, HP
Cabrera, RM
Jolly, CA
AF Gulvady, Apeksha A.
Ciolino, Henry P.
Cabrera, Robert M.
Jolly, Christopher A.
TI Resveratrol inhibits the deleterious effects of diet-induced obesity on
thymic function
SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY
LA English
DT Article
DE Thymus; Mouse; Obesity; Resveratrol; T cell; Diet
ID CALORIC RESTRICTION; MICE; METABOLISM; INVOLUTION; CHILDREN; DISEASE
AB Obesity is associated with an increased risk of infectious diseases. It has been shown to have deleterious effects on cell-mediated immunity, including reducing thymocyte numbers and altering responses of thymocytes to pathogens. In the current study, we examined the efficacy of the antiobesity phytochemical resveratrol in preventing the deleterious effects of a high-fat diet on thymic anatomy and function. Compared to C57BI/6 male mice fed a low-fat diet, mice on a high-fat diet had a significant increase in thymic weight and lipid content, and a disrupted anatomy, including a reduction of the medullary compartment and absence of a corticomedullary junction. There were a decrease in thymic cellularity and mature T-cell output, and a disrupted T-cell maturation, as evidenced by increased double-negative and decreased single- and double-positive thymocytes. Mice that had been fed resveratrol along with a high-fat diet had a dose-dependent reversal in all these parameters. Western blots from thymi showed that obese mice had lower levels of the key stimulators of lipid metabolism, phospho-5' adenosine monophosphate-activated protein kinase and its downstream target, carnitine palmitoyl transferase-1; this was restored to normal levels in resveratrol-fed mice. Resveratrol also reversed an increase in glycerol-3-phosphate acyltransferase-1, the enzyme that catalyzes the first step in triglycerol synthesis. Taken together, these results indicate that resveratrol is a potent inhibitor of the deleterious effects of diet-induced obesity on thymic anatomy and function, and this may hold promise in preventing obesity-related deficits in cell-mediated immunity. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Gulvady, Apeksha A.; Cabrera, Robert M.; Jolly, Christopher A.] Univ Texas Austin, Dept Nutr Sci, Dell Pediat Res Inst, Austin, TX 78723 USA.
[Ciolino, Henry P.] NCI, Off Canc Ctr, Rockville, MD 20852 USA.
RP Jolly, CA (reprint author), Univ Texas Austin, Dept Nutr Sci, Dell Pediat Res Inst, 1400 Barbara Jordan Blvd,R1800, Austin, TX 78723 USA.
EM jolly@austin.utexas.edu
NR 27
TC 6
Z9 6
U1 2
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0955-2863
EI 1873-4847
J9 J NUTR BIOCHEM
JI J. Nutr. Biochem.
PD SEP
PY 2013
VL 24
IS 9
BP 1625
EP 1633
DI 10.1016/j.jnutbio.2013.02.003
PG 9
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA 204XP
UT WOS:000323404900010
PM 23561698
ER
PT J
AU Jonnalagadda, SR
Del Fiol, G
Medlin, R
Weir, C
Fiszman, M
Mostafa, J
Liu, HF
AF Jonnalagadda, Siddhartha Reddy
Del Fiol, Guilherme
Medlin, Richard
Weir, Charlene
Fiszman, Marcelo
Mostafa, Javed
Liu, Hongfang
TI Automatically extracting sentences from Medline citations to support
clinicians' information needs
SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
LA English
DT Article
DE clinical decision support; information needs; knowledge summary; natural
language processing
ID CLASSIFICATION MODELS; PHYSICIANS; QUESTIONS; CARE; SEARCH; MET
AB Objective
Online health knowledge resources contain answers to most of the information needs raised by clinicians in the course of care. However, significant barriers limit the use of these resources for decision-making, especially clinicians' lack of time. In this study we assessed the feasibility of automatically generating knowledge summaries for a particular clinical topic composed of relevant sentences extracted from Medline citations.
Methods
The proposed approach combines information retrieval and semantic information extraction techniques to identify relevant sentences from Medline abstracts. We assessed this approach in two case studies on the treatment alternatives for depression and Alzheimer's disease.
Results
A total of 515 of 564 (91.3%) sentences retrieved in the two case studies were relevant to the topic of interest. About one-third of the relevant sentences described factual knowledge or a study conclusion that can be used for supporting information needs at the point of care.
Conclusions
The high rate of relevant sentences is desirable, given that clinicians' lack of time is one of the main barriers to using knowledge resources at the point of care. Sentence rank was not significantly associated with relevancy, possibly due to most sentences being highly relevant. Sentences located closer to the end of the abstract and sentences with treatment and comparative predications were likely to be conclusive sentences. Our proposed technical approach to helping clinicians meet their information needs is promising. The approach can be extended for other knowledge resources and information need types.
C1 [Jonnalagadda, Siddhartha Reddy; Liu, Hongfang] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA.
[Del Fiol, Guilherme; Weir, Charlene] Univ Utah, Dept Biomed Informat, Salt Lake City, UT USA.
[Fiszman, Marcelo] Natl Lib Med, Lister Hill Ctr, Bethesda, MD USA.
[Medlin, Richard; Mostafa, Javed] Univ N Carolina, Chapel Hill, NC USA.
[Weir, Charlene] VA Med Ctr, Salt Lake City, UT USA.
RP Jonnalagadda, SR (reprint author), Mayo Clin, Dept Hlth Sci Res, 200 1st St SW, Rochester, MN 55905 USA.
EM siddhartha@mayo.edu
OI Del Fiol, Guilherme/0000-0001-9954-6799
FU NSF [1117286]; NIH CTSA [UL1TR000083]; Agency for Healthcare Research
and Quality [K01HS018352]
FX JM and RM have been partially funded for this research through NSF Award
1117286 and the NIH CTSA Award UL1TR000083. GDF was supported by grant
number K01HS018352 from the Agency for Healthcare Research and Quality.
NR 34
TC 7
Z9 7
U1 2
U2 14
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1067-5027
J9 J AM MED INFORM ASSN
JI J. Am. Med. Inf. Assoc.
PD SEP
PY 2013
VL 20
IS 5
BP 995
EP 1000
DI 10.1136/amiajnl-2012-001347
PG 6
WC Computer Science, Information Systems; Computer Science,
Interdisciplinary Applications; Health Care Sciences & Services;
Information Science & Library Science; Medical Informatics
SC Computer Science; Health Care Sciences & Services; Information Science &
Library Science; Medical Informatics
GA 201UJ
UT WOS:000323168200027
PM 23100128
ER
PT J
AU Shaikh, Q
Kamal, AK
AF Shaikh, Quratulain
Kamal, Ayeesha Kamran
TI My patient has carotid stenosis. Should he get stenting or
endarterectomy?
SO JOURNAL OF THE PAKISTAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Kamal, Ayeesha Kamran] Aga Khan Univ Hosp, Fogarty Int Ctr, Int Cerebrovasc Translat Clin Res Training Progra, Stroke Serv & Vasc Fellowship Program, Karachi, Pakistan.
Aga Khan Univ Hosp, Natl Inst Neurol Disorders & Stroke, Karachi, Pakistan.
RP Kamal, AK (reprint author), Aga Khan Univ Hosp, Fogarty Int Ctr, Int Cerebrovasc Translat Clin Res Training Progra, Stroke Serv & Vasc Fellowship Program, Karachi, Pakistan.
EM ayeesha.kamal@aku.edu
FU FIC NIH HHS [D43TW008660, D43 TW008660]
NR 2
TC 0
Z9 0
U1 1
U2 1
PU PAKISTAN MEDICAL ASSOC
PI KARACHI
PA PMA HOUSE, AGA KHAN III RD, KARACHI, 00000, PAKISTAN
SN 0030-9982
J9 J PAK MED ASSOC
JI J. Pak. Med. Assoc.
PD SEP
PY 2013
VL 63
IS 9
BP 1201
EP 1201
PG 1
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 205QL
UT WOS:000323459500029
PM 24601208
ER
PT J
AU Priola, SA
Ward, AE
McCall, SA
Trifilo, M
Choi, YP
Solforosi, L
Williamson, RA
Cruite, JT
Oldstone, MBA
AF Priola, Suzette A.
Ward, Anne E.
McCall, Sherman A.
Trifilo, Matthew
Choi, Young Pyo
Solforosi, Laura
Williamson, R. Anthony
Cruite, Justin T.
Oldstone, Michael B. A.
TI Lack of Prion Infectivity in Fixed Heart Tissue from Patients with
Creutzfeldt-Jakob Disease or Amyloid Heart Disease
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY; CHRONIC WASTING DISEASE; SINGLE
AMINO-ACID; TRANSGENIC MICE; INCUBATION-TIME; PERIPHERAL-NERVES;
BLOOD-TRANSFUSION; HAMSTER SCRAPIE; SKELETAL-MUSCLE; NERVOUS-SYSTEM
AB In most forms of prion disease, infectivity is present primarily in the central nervous system or immune system organs such as spleen and lymph node. However, a transgenic mouse model of prion disease has demonstrated that prion infectivity can also be present as amyloid deposits in heart tissue. Deposition of infectious prions as amyloid in human heart tissue would be a significant public health concern. Although abnormal disease-associated prion protein (PrPSc) has not been detected in heart tissue from several amyloid heart disease patients, it has been observed in the heart tissue of a patient with sporadic Creutzfeldt-Jakob Disease (sCJD), the most common form of human prion disease. In order to determine whether prion infectivity can be found in heart tissue, we have inoculated formaldehyde fixed brain and heart tissue from two sCJD patients, as well as prion protein positive fixed heart tissue from two amyloid heart disease patients, into transgenic mice overexpressing the human prion protein. Although the sCJD brain samples led to clinical or subclinical prion infection and deposition of PrPSc in the brain, none of the inoculated heart samples resulted in disease or the accumulation of PrPSc. Thus, our results suggest that prion infectivity is not likely present in cardiac tissue from sCJD or amyloid heart disease patients.
C1 [Priola, Suzette A.; Ward, Anne E.; Choi, Young Pyo] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT USA.
[McCall, Sherman A.] USAMRIID, Ft Detrick, MD USA.
[Trifilo, Matthew; Solforosi, Laura; Williamson, R. Anthony; Cruite, Justin T.; Oldstone, Michael B. A.] Scripps Res Inst, Dept Immunol Microbial Sci, La Jolla, CA 92037 USA.
RP Priola, SA (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT USA.
EM spriola@niaid.nih.gov
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health; USPHS [AG04342]
FX This research was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, and USPHS grant AG04342.
NR 52
TC 1
Z9 1
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD SEP
PY 2013
VL 87
IS 17
BP 9501
EP 9510
DI 10.1128/JVI.00692-13
PG 10
WC Virology
SC Virology
GA 201NO
UT WOS:000323148500010
PM 23785217
ER
PT J
AU Chen, ZC
Sosnovtsev, SV
Bok, K
Parra, GI
Makiya, M
Agulto, L
Green, KY
Purcell, RH
AF Chen, Zhaochun
Sosnovtsev, Stanislav V.
Bok, Karin
Parra, Gabriel I.
Makiya, Michelle
Agulto, Liane
Green, Kim Y.
Purcell, Robert H.
TI Development of Norwalk Virus-Specific Monoclonal Antibodies with
Therapeutic Potential for the Treatment of Norwalk Virus Gastroenteritis
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID BLOOD GROUP ANTIGENS; HEPATITIS-C VIRUS; INFECTIOUS NONBACTERIAL
GASTROENTERITIS; INFLUENZA-A-VIRUSES; MEMORY B-CELLS; 3-DIMENSIONAL
STRUCTURE; NEUTRALIZING ANTIBODY; PROTECTIVE ANTIGEN; STRUCTURAL BASIS;
VACCINIA VIRUS
AB Passive immunoprophylaxis or immunotherapy with norovirus-neutralizing monoclonal antibodies (MAbs) could be a useful treatment for high-risk populations, including infants and young children, the elderly, and certain patients who are debilitated or immunocompromised. In order to obtain antinorovirus MAbs with therapeutic potential, we stimulated a strong adaptive immune response in chimpanzees to the prototype norovirus strain Norwalk virus (NV) (genogroup I. 1). A combinatorial phage Fab display library derived from mRNA of the chimpanzees' bone marrow was prepared, and four distinct Fabs reactive with Norwalk recombinant virus-like particles (rVLPs) were recovered, with estimated binding affinities in the subnanomolar range. Mapping studies showed that the four Fabs recognized three different conformational epitopes in the protruding (P) domain of NV VP1, the major capsid protein. The epitope of one of the Fabs, G4, was further mapped to a specific site involving a key amino acid residue, Gly365. One additional specific Fab (F11) was recovered months later from immortalized memory B cells and partially characterized. The anti-NV Fabs were converted into full-length IgG (MAbs) with human gamma 1 heavy chain constant regions. The anti-NV MAbs were tested in the two available surrogate assays for Norwalk virus neutralization, which showed that the MAbs could block carbohydrate binding and inhibit hemagglutination by NV rVLP. By mixing a single MAb with live Norwalk virus prior to challenge, MAbs D8 and B7 neutralized the virus and prevented infection in a chimpanzee. Because chimpanzee immunoglobulins are virtually identical to human immunoglobulins, these chimpanzee anticapsid MAbs may have a clinical application.
C1 [Chen, Zhaochun; Makiya, Michelle; Agulto, Liane; Purcell, Robert H.] NIAID, Infect Dis Lab, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Sosnovtsev, Stanislav V.; Bok, Karin; Parra, Gabriel I.; Green, Kim Y.] NIAID, Infect Dis Lab, Natl Inst Hlth, Cardiovasc Sect, Bethesda, MD 20892 USA.
RP Chen, ZC (reprint author), NIAID, Infect Dis Lab, Natl Inst Hlth, Bethesda, MD 20892 USA.
EM zchen@niaid.nih.gov; kgreen@niaid.nih.gov
OI Parra, Gabriel/0000-0002-1102-4740
FU Intramural Research Program of the NIAID, NIH
FX This research was supported by the Intramural Research Program of the
NIAID, NIH.
NR 68
TC 22
Z9 22
U1 1
U2 10
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD SEP
PY 2013
VL 87
IS 17
BP 9547
EP 9557
DI 10.1128/JVI.01376-13
PG 11
WC Virology
SC Virology
GA 201NO
UT WOS:000323148500014
PM 23785216
ER
PT J
AU Magadan, JG
Khurana, S
Das, SR
Frank, GM
Stevens, J
Golding, H
Bennink, JR
Yewdell, JW
AF Magadan, Javier G.
Khurana, Surender
Das, Suman R.
Frank, Gregory M.
Stevens, James
Golding, Hana
Bennink, Jack R.
Yewdell, Jonathan W.
TI Influenza A Virus Hemagglutinin Trimerization Completes Monomer Folding
and Antigenicity
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID VIRAL MEMBRANE-PROTEINS; INTRACELLULAR-TRANSPORT; RECEPTOR-BINDING;
MONOCLONAL-ANTIBODIES; NEUTRALIZING ANTIBODY; ENDOPLASMIC-RETICULUM;
GOLGI-COMPLEX; FUSION; CELLS; SITE
AB Influenza A virus (IAV) remains an important human pathogen largely because of antigenic drift, the rapid emergence of anti-body escape mutants that precludes durable vaccination. The most potent neutralizing antibodies interact with cognate epitopes in the globular "head" domain of hemagglutinin (HA), a homotrimeric glycoprotein. The H1 HA possesses five distinct regions defined by a large number of mouse monoclonal antibodies (MAbs), i.e., Ca1, Ca2, Cb, Sa, and Sb. Ca1-Ca2 sites require HA trimerization to attain full antigenicity, consistent with their locations on opposite sides of the trimer interface. Here, we show that full antigenicity of Cb and Sa sites also requires HA trimerization, as revealed by immunofluorescence microscopy of IAV-infected cells and biochemically by pulse-chase radiolabeling experiments. Surprisingly, epitope antigenicity acquired by HA trimerization persists following acid triggering of the globular domains dissociation and even after proteolytic release of monomeric heads from acid-treated HA. Thus, the requirement for HA trimerization by trimer-specific MAbs mapping to the Ca, Cb, and Sa sites is not dependent upon the bridging of adjacent monomers in the native HA trimer. Rather, complete antigenicity of HA (and, by inference, immunogenicity) requires a final folding step that accompanies its trimerization. Once this conformational change occurs, HA trimers themselves would not necessarily be required to induce a highly diverse neutralizing response to epitopes in the globular domain.
C1 [Magadan, Javier G.; Das, Suman R.; Bennink, Jack R.; Yewdell, Jonathan W.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
[Khurana, Surender; Frank, Gregory M.; Golding, Hana] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
[Stevens, James] Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA.
RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
EM jyewdell@niaid.nih.gov
FU Division of Intramural Research of the National Institute of Allergy and
Infectious Diseases
FX This work was supported by the Division of Intramural Research of the
National Institute of Allergy and Infectious Diseases.
NR 47
TC 11
Z9 11
U1 1
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD SEP
PY 2013
VL 87
IS 17
BP 9742
EP 9753
DI 10.1128/JVI.00471-13
PG 12
WC Virology
SC Virology
GA 201NO
UT WOS:000323148500032
PM 23824811
ER
PT J
AU Arnold, MM
Barro, M
Patton, JT
AF Arnold, Michelle M.
Barro, Mario
Patton, John T.
TI Rotavirus NSP1 Mediates Degradation of Interferon Regulatory Factors
through Targeting of the Dimerization Domain
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID INNATE IMMUNE-RESPONSE; VIRAL NUCLEIC-ACIDS; CRYSTAL-STRUCTURE;
TRANSCRIPTION FACTOR; ANTIVIRAL RESPONSES; IRF FAMILY; ACTIVATION;
PROTEIN; PHOSPHORYLATION; EXPRESSION
AB Rotavirus nonstructural protein NSP1 can inhibit expression of interferon (IFN) and IFN-stimulated gene products by inducing proteasome-mediated degradation of IFN-regulatory factors (IRFs), including IRF3, IRF5, and IRF7. All IRF proteins share an N-terminal DNA-binding domain (DBD), and IRF3, IRF5, and IRF7 contain a similar C-proximal IRF association domain (IAD) that mediates IRF dimerization. An autoinhibitory domain (ID) at the extreme C terminus interacts with the IAD, burying residues necessary for IRF dimerization. Phosphorylation of serine/threonine residues in the ID induces charge repulsions that unmask the IAD, enabling IRF dimerization and subsequent nuclear translocation. To define the region of IRF proteins targeted for degradation by NSP1, we generated IRF3 and IRF7 truncation mutants and transiently expressed each with simian SA11-4F NSP1. These assays indicated that the IAD represented a necessary and sufficient target for degradation. Because NSP1 did not mediate degradation of truncated forms of the IAD, NSP1 likely requires a structurally intact IAD for recognition and targeting of IRF proteins. IRF9, which contains an IAD-like region that directs interactions with signal inducer and activator of transcription (STAT) proteins, was also targeted for degradation by NSP1, while IRF1, which lacks an IAD, was not. Analysis of mutant forms of IRF3 unable to undergo dimerization or that were constitutively dimeric showed that both were targeted for degradation by NSP1. These results indicate that SA11-4F NSP1 can induce degradation of inactive and activated forms of IAD-containing IRF proteins (IRF3 to IRF9), allowing a multipronged attack on IFN-based pathways that promote antiviral innate and adaptive immune responses.
C1 [Arnold, Michelle M.; Barro, Mario; Patton, John T.] NIAID, Rotavirus Mol Biol Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Patton, JT (reprint author), NIAID, Rotavirus Mol Biol Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jpatton@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 65
TC 18
Z9 20
U1 0
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD SEP
PY 2013
VL 87
IS 17
BP 9813
EP 9821
DI 10.1128/JVI.01146-13
PG 9
WC Virology
SC Virology
GA 201NO
UT WOS:000323148500038
PM 23824805
ER
PT J
AU Petrovas, C
Yamamoto, T
Price, DA
Rao, SS
Klatt, NR
Brenchley, JM
Douek, DC
Gostick, E
Angermann, BR
Grossman, Z
Macallan, DC
Meier-Schellersheim, M
Koup, RA
AF Petrovas, Constantinos
Yamamoto, Takuya
Price, David A.
Rao, Srinivas S.
Klatt, Nichole R.
Brenchley, Jason M.
Douek, Daniel C.
Gostick, Emma
Angermann, Bastian R.
Grossman, Zvi
Macallan, Derek C.
Meier-Schellersheim, Martin
Koup, Richard A.
TI High Production Rates Sustain In Vivo Levels of PD-1(high) Simian
Immunodeficiency Virus-Specific CD8 T Cells in the Face of Rapid
Clearance
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HIV-INFECTION; RHESUS MACAQUES; PD-1; TURNOVER; LYMPHOCYTES; EXPRESSION;
CD4(+); VACCINATION; REGULATOR; SIVMAC251
AB Programmed Death 1 (PD-1) expression by human/simian immunodeficiency virus (HIV/SIV)-specific CD8 T cells has been associated with defective cytokine production and reduced in vitro proliferation capacity. However, the cellular mechanisms that sustain PD-1(high) virus-specific CD8 T cell responses during chronic infection are unknown. Here, we show that the PD-1(high) phenotype is associated with accelerated in vivo CD8 T cell turnover in SIV-infected rhesus macaques, especially within the SIV-specific CD8 T cell pool. Mathematical modeling of 5-bromo-2' deoxyuridine (BrdU) labeling dynamics demonstrated a significantly increased generation rate of PD-1(high) compared to PD-1(low) CD8 T cells in all memory compartments. Simultaneous analysis of Ki67 and BrdU kinetics revealed a complex in vivo turnover profile whereby only a small fraction of PD-1(high) cells, but virtually all PD-1(low) cells, returned to rest after activation. Similar kinetics operated in both chronic and acute SIV infection. Our data suggest that the persistence of PD-1(high) SIV-specific CD8 T cells in chronic infection is maintained in vivo by a mechanism involving high production coupled with a high disappearance rate.
C1 [Petrovas, Constantinos; Yamamoto, Takuya; Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Price, David A.; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Rao, Srinivas S.] NIAID, Lab Anim Med, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Price, David A.; Gostick, Emma] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff CF10 3AX, S Glam, Wales.
[Klatt, Nichole R.; Brenchley, Jason M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Angermann, Bastian R.; Meier-Schellersheim, Martin] NIAID, Program Syst Immunol & Infect Dis Modeling, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Grossman, Zvi] Tel Aviv Univ, Sch Med, IL-69978 Tel Aviv, Israel.
[Grossman, Zvi] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Macallan, Derek C.] Univ London, St Georges Hosp, Div Clin Sci, Infect & Immun Res Ctr, London, England.
RP Petrovas, C (reprint author), NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM petrovasc@mail.nih.gov; mms@niaid.nih.gov
RI Yamamoto, Takuya/L-2642-2013; Price, David/C-7876-2013;
OI Yamamoto, Takuya/0000-0003-3753-1211; Price, David/0000-0001-9416-2737;
Macallan, Derek/0000-0002-3014-7148
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health. D. A. P. is a Wellcome Trust Senior Investigator.
NR 24
TC 5
Z9 5
U1 0
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD SEP
PY 2013
VL 87
IS 17
BP 9836
EP 9844
DI 10.1128/JVI.01001-13
PG 9
WC Virology
SC Virology
GA 201NO
UT WOS:000323148500040
PM 23824823
ER
PT J
AU Bamunusinghe, D
Liu, QP
Lu, XY
Oler, A
Kozak, CA
AF Bamunusinghe, Devinka
Liu, Qingping
Lu, Xiaoyu
Oler, Andrew
Kozak, Christine A.
TI Endogenous Gammaretrovirus Acquisition in Mus musculus Subspecies
Carrying Functional Variants of the XPR1 Virus Receptor
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID MURINE LEUKEMIA-VIRUS; CELL-SURFACE RECEPTOR; MOUSE XENOTROPIC
GAMMARETROVIRUSES; LONG TERMINAL REPEATS; MITOCHONDRIAL-DNA; LABORATORY
MOUSE; RETROVIRUS XMRV; WILD MICE; ORIGIN; SEQUENCE
AB The xenotropic and polytropic mouse leukemia viruses (X-MLVs and P-MLVs, respectively) have different host ranges but use the same functionally polymorphic receptor, XPR1, for entry. Endogenous retroviruses (ERVs) of these 2 gammaretrovirus sub-types are largely segregated in different house mouse subspecies, but both MLV types are found in the classical strains of laboratory mice, which are genetic mosaics of 3 wild mouse subspecies. To describe the subspecies origins of laboratory mouse XP-MLV ERVs and their coevolutionary trajectory with their XPR1 receptor, we screened the house mouse subspecies for known and novel Xpr1 variants and for the individual full-length XP-MLV ERVs found in the sequenced C57BL mouse genome. The 12 X-MLV ERVs predate the origins of laboratory mice; they were all traced to Japanese wild mice and are embedded in the 5% of the laboratory mouse genome derived from the Asian Mus musculus musculus and, in one case, in the <1% derived from M. m. castaneus. While all 31 P-MLV ERVs map to the 95% of the laboratory mouse genome derived from P-MLV-infected M. m. domesticus, no C57BL P-MLV ERVs were found in wild M. m. domesticus. All M. m. domesticus mice carry the fully permissive XPR1 receptor allele, but all of the various restrictive XPR1 receptors, including the X-MLV-restricting laboratory mouse Xpr1(n) and a novel M. m. castaneus allele, originated in X-MLV-infected Asian mice. Thus, P-MLV ERVs show more insertional polymorphism than X-MLVs, and these differences in ERV acquisition and fixation are linked to subspecies-specific and functionally distinct XPR1 receptor variants.
C1 [Bamunusinghe, Devinka; Liu, Qingping; Lu, Xiaoyu; Kozak, Christine A.] NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA.
[Oler, Andrew] NIAID, Bioinformat & Computat Biosci Branch, Bethesda, MD 20892 USA.
RP Kozak, CA (reprint author), NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA.
EM ckozak@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases, Bethesda, MD
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, Bethesda, MD.
NR 56
TC 9
Z9 9
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD SEP
PY 2013
VL 87
IS 17
BP 9845
EP 9855
DI 10.1128/JVI.01264-13
PG 11
WC Virology
SC Virology
GA 201NO
UT WOS:000323148500041
PM 23824809
ER
PT J
AU Ke, RA
Lloyd-Smith, JO
AF Ke, Ruian
Lloyd-Smith, James O.
TI Coadaptive Stability of Interfering Particles with HIV-1 When There Is
an Evolutionary Conflict
SO JOURNAL OF VIROLOGY
LA English
DT Letter
ID IMMUNODEFICIENCY-VIRUS TYPE-1; DIMERIZATION; INFECTION; GENOMES; DESIGN
C1 [Ke, Ruian; Lloyd-Smith, James O.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA.
[Lloyd-Smith, James O.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Ke, RA (reprint author), Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA.
EM ruian@ucla.edu
RI Lloyd-Smith, James/K-4080-2012
OI Lloyd-Smith, James/0000-0001-7941-502X
NR 9
TC 1
Z9 1
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD SEP
PY 2013
VL 87
IS 17
BP 9959
EP 9959
DI 10.1128/JVI.00705-13
PG 1
WC Virology
SC Virology
GA 201NO
UT WOS:000323148500056
PM 23943739
ER
PT J
AU Gao, N
Yoon, GS
Liu, X
Mi, X
Chen, W
Standiford, TJ
Yu, FSX
AF Gao, N.
Yoon, G. Sang
Liu, X.
Mi, X.
Chen, W.
Standiford, T. J.
Yu, F-S X.
TI Genome-wide transcriptional analysis of differentially expressed genes
in flagellin-pretreated mouse corneal epithelial cells in response to
Pseudomonas aeruginosa: involvement of S100A8/A9
SO MUCOSAL IMMUNOLOGY
LA English
DT Article
ID TOLL-LIKE RECEPTOR; IN-VITRO; BACTERIAL-INFECTION; INNATE IMMUNITY;
UP-REGULATION; CALPROTECTIN; DEFENSE; PROTEIN; INFLAMMATION; BINDING
AB We previously showed that pre-exposure of the cornea to Toll-like receptor 5 ligand flagellin induces profound mucosal innate protection against infections by modifying gene expression. Taking advantage of easily procurable epithelial cell population, this study is the first report to use genome-wide cDNA microarray approach to document genes associated with flagellin-induced protection against Pseudomonas aeruginosa in corneal epithelial cells (CECs). Infection altered the expression of 675 genes (497 up and 178 down), while flagellin pretreatment followed by infection resulted in a great increase in 890 gene upregulated and 37 genes downregulated. Comparing these two groups showed 209 differentially expressed genes (157 up, 52 down). Notably, among 114 genes categorized as defense related, S100A8/A9 are the two most highly induced genes by flagellin, and their expression in the corneal was confirmed by realtime PCR and immunohistochemistry. Neutralization of S100A8 and, to a less extent, A9, resulted in significantly increased bacterial burden and severe keratitis. Collectively, our study identifies many differentially expressed genes by flagellin in CECs in response to Pseudomonas. These novel gene expression signatures provide new insights and clues into the nature of protective mechanisms established by flagellin and new therapeutic targets for reducing inflammation and for controlling microbial infection.
C1 [Gao, N.; Mi, X.; Yu, F-S X.] Wayne State Univ, Sch Med, Dept Ophthalmol, Detroit, MI 48202 USA.
[Yoon, G. Sang; Liu, X.; Yu, F-S X.] Wayne State Univ, Sch Med, Dept Anat & Cell Biol, Detroit, MI USA.
[Liu, X.] Chinese Acad Med Sci, Dept Ophthalmol, Peking Union Med Coll Hosp, Beijing 100730, Peoples R China.
[Chen, W.] Genom Core Lab Natl Inst Diabet & Digest & Kidney, Bethesda, MD USA.
[Standiford, T. J.] Univ Michigan, Med Ctr, Dept Internal Med, Div Pulm & Crit Care Med, Ann Arbor, MI 48109 USA.
RP Yu, FSX (reprint author), Wayne State Univ, Sch Med, Dept Ophthalmol, Detroit, MI 48202 USA.
EM fyu@med.wayne.edu
FU NIH/NEI [R01-EY010869, R01-EY017960, P30-EY004068, R01-HL097564];
Midwest Eye Bank; Research to Prevent Blindness
FX This study was supported by grants NIH/NEI R01-EY010869, R01-EY017960,
P30-EY004068, R01-HL097564, Midwest Eye Bank, Research to Prevent
Blindness.
NR 66
TC 8
Z9 8
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1933-0219
J9 MUCOSAL IMMUNOL
JI Mucosal Immunol.
PD SEP
PY 2013
VL 6
IS 5
BP 993
EP 1005
DI 10.1038/mi.2012.137
PG 13
WC Immunology
SC Immunology
GA 203YV
UT WOS:000323331800013
PM 23340821
ER
PT J
AU Overstreet, MG
Gaylo, A
Angermann, BR
Hughson, A
Hyun, YM
Lambert, K
Acharya, M
Billroth-MacLurg, AC
Rosenberg, AF
Topham, DJ
Yagita, H
Kim, M
Lacy-Hulbert, A
Meier-Schellersheim, M
Fowell, DJ
AF Overstreet, Michael G.
Gaylo, Alison
Angermann, Bastian R.
Hughson, Angela
Hyun, Young-Min
Lambert, Kris
Acharya, Mridu
Billroth-MacLurg, Alison C.
Rosenberg, Alexander F.
Topham, David J.
Yagita, Hideo
Kim, Minsoo
Lacy-Hulbert, Adam
Meier-Schellersheim, Martin
Fowell, Deborah J.
TI Inflammation-induced interstitial migration of effector CD4(+) T cells
is dependent on integrin alpha(V)
SO NATURE IMMUNOLOGY
LA English
DT Article
ID DELAYED-TYPE HYPERSENSITIVITY; IN-VIVO; DENDRITIC CELLS; LEUKOCYTE
MIGRATION; INFLUENZA INFECTION; LYMPH-NODES; V INTEGRINS; FIBRONECTIN;
EXPRESSION; MOTILITY
AB Leukocytes must traverse inflamed tissues to effectively control local infection. Although motility in dense tissues seems to be integrin independent and based on actomyosin-mediated protrusion and contraction, during inflammation, changes to the extracellular matrix (ECM) may necessitate distinct motility requirements. Indeed, we found that the interstitial motility of T cells was critically dependent on Arg-Gly-Asp (RGD)-binding integrins in the inflamed dermis. Inflammation-induced deposition of fibronectin was functionally linked to higher expression of integrin alpha(V) on effector CD4(+) T cells. By intravital multiphoton imaging, we found that the motility of CD4(+) T cells was dependent on alpha(V) expression. Selective blockade or knockdown of alpha(V) arrested T helper type 1 (T(H)1) cells in the inflamed tissue and attenuated local effector function. Our data demonstrate context-dependent specificity of lymphocyte movement in inflamed tissues that is essential for protective immunity.
C1 [Overstreet, Michael G.; Gaylo, Alison; Hughson, Angela; Hyun, Young-Min; Lambert, Kris; Billroth-MacLurg, Alison C.; Topham, David J.; Kim, Minsoo; Fowell, Deborah J.] Univ Rochester, Aab Inst Biomed Sci, David H Smith Ctr Vaccine Biol & Immunol, Rochester, NY 14627 USA.
[Overstreet, Michael G.; Gaylo, Alison; Hyun, Young-Min; Billroth-MacLurg, Alison C.; Topham, David J.; Kim, Minsoo; Fowell, Deborah J.] Univ Rochester, Dept Microbiol & Immunol, Rochester, NY USA.
[Angermann, Bastian R.; Meier-Schellersheim, Martin] NIAID, Computat Biol Unit, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
[Acharya, Mridu; Lacy-Hulbert, Adam] Massachusetts Gen Hosp, Dept Pediat, Program Dev Immunol, Boston, MA 02114 USA.
[Acharya, Mridu; Lacy-Hulbert, Adam] Harvard Univ, Sch Med, Boston, MA USA.
[Rosenberg, Alexander F.] Univ Rochester, Med Ctr, Div Allergy Immunol & Rheumatol, Rochester, NY 14642 USA.
[Yagita, Hideo] Juntendo Univ, Dept Immunol, Tokyo, Japan.
RP Fowell, DJ (reprint author), Univ Rochester, Aab Inst Biomed Sci, David H Smith Ctr Vaccine Biol & Immunol, Rochester, NY 14627 USA.
EM deborah_fowell@urmc.rochester.edu
OI Lacy-Hulbert, Adam/0000-0003-2162-0156
FU US National Institutes of Health [AI072690, AI088427, HL018208,
HL087088, AI089079]; American Heart Association [11SDG7520018]; National
Institute of Allergy and Infectious Diseases
FX We thank N. Killeen (University of California, San Francisco) for WT15
mice; R. Locksley (University of California, San Francisco) for
IFN-gamma reporter mice (Yeti mice); M. Nussenzweig (The Rockefeller
University) for CD11c-YFP mice; R. Hynes (MIT) for Itga5fl/fl
mice; B. Leon and F. Lund (University of Alabama) for H.
polygyrus-infected tissue; R. Germain and J. Egen for technical
assistance; K. Kasischke, L. Callahan, E. Brown and the University of
Rochester Medical Center Multiphoton Core for support; Kihong Lim for
technical assistance; J. Miller and S. Georas for comments on the
manuscript; and members of the Fowell and Kim laboratories for
discussions and support. Supported by the US National Institutes of
Health (AI072690 and AI088427 to D. J. F.; HL018208 and HL087088 to M.
K.; and AI089079 to M.G.O.), the American Heart Association
(11SDG7520018 to Y.-M.H.) and the intramural program of the National
Institute of Allergy and Infectious Diseases (B. R. A. and M.M.-S.).
NR 55
TC 36
Z9 36
U1 0
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 SEP
PY 2013
VL 14
IS 9
BP 949
EP +
DI 10.1038/ni.2682
PG 12
WC Immunology
SC Immunology
GA 204OS
UT WOS:000323377700012
PM 23933892
ER
PT J
AU Song, R
Zhang, HY
Peng, XQ
Su, RB
Yang, RF
Li, J
Xi, ZX
Gardner, EL
AF Song, Rui
Zhang, Hai-Ying
Peng, Xiao-Qing
Su, Rui-Bin
Yang, Ri-Fang
Li, Jin
Xi, Zheng-Xiong
Gardner, Eliot L.
TI Dopamine D-3 receptor deletion or blockade attenuates cocaine-induced
conditioned place preference in mice
SO NEUROPHARMACOLOGY
LA English
DT Article
DE Cocaine; Dopamine; D-3 receptor; YQA-14; Reward; Conditioned place
preference
ID WILD-TYPE MICE; AGONIST 7-OH-DPAT; SEEKING BEHAVIOR; KNOCKOUT MICE;
RAT-BRAIN; RHESUS-MONKEYS; MUTANT MICE; LOCALIZATION; PHARMACOLOGY;
ANTAGONISTS
AB The dopamine (DA) D-3 receptor (D3R) has received much attention in medication development for treatment of addiction. However, the functional role of the D3R in drug reward and addiction has been a matter of debate. We recently reported that D-3 receptor-knockout (D-3(-/-)) mice display increased vulnerability to cocaine self-administration, which we interpret as a compensatory response to attenuated cocaine reward after D3R deletion. Here we report that D-3(-/-) mice displayed attenuated cocaine-induced conditioned place response (CPP) compared to wild-type mice. Similarly, blockade of brain D(3)Rs by YQA-14, a novel DA D-3 receptor antagonist, significantly and dose-dependently inhibits acquisition and expression of cocaine-induced CPP in WT mice, but not in D-3(-/-) mice. These findings suggest that: 1) D(3)Rs play an important role in mediating cocaine's rewarding effects; and 2) YQA-14 is a highly potent and selective D3R antagonist in vivo, which deserves further study as a candidate for treatment of cocaine addiction. Published by Elsevier Ltd.
C1 [Song, Rui; Zhang, Hai-Ying; Peng, Xiao-Qing; Xi, Zheng-Xiong; Gardner, Eliot L.] NIDA, Intramural Res Program, Baltimore, MD 21224 USA.
[Song, Rui; Su, Rui-Bin; Yang, Ri-Fang; Li, Jin] Beijing Inst Pharmacol & Toxicol, Beijing 100850, Peoples R China.
RP Li, J (reprint author), Beijing Inst Pharmacol & Toxicol, Beijing 100850, Peoples R China.
EM lijin@nic.bmi.ac.cn; zxi@intra.nida.nih.gov
OI PENG, XIAOQING/0000-0002-7272-5428; Yang, Rifang/0000-0001-8087-9614;
Zhang, Haiying/0000-0003-0593-5940
FU U.S. National Institute on Drug Abuse Intramural Research Program;
National Basic Research Program of China [2009CB522008]; Natural Science
Foundation of China [81102425]
FX This work was supported by the U.S. National Institute on Drug Abuse
Intramural Research Program, the National Basic Research Program of
China (Grant No. 2009CB522008) and the Natural Science Foundation of
China (Grant No. 81102425).
NR 36
TC 11
Z9 12
U1 0
U2 13
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD SEP
PY 2013
VL 72
BP 82
EP 87
DI 10.1016/j.neuropharm.2013.04.042
PG 6
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 185CC
UT WOS:000321941800010
PM 23643749
ER
PT J
AU Van Swearingen, AED
Sanchez, CL
Frisbee, SM
Williams, A
Walker, QD
Korach, KS
Kuhn, CM
AF Van Swearingen, Amanda E. D.
Sanchez, Cristina L.
Frisbee, Suzanne M.
Williams, Antonia
Walker, Q. David
Korach, Kenneth S.
Kuhn, Cynthia M.
TI Estradiol replacement enhances cocaine-stimulated locomotion in female
C57BL/6 mice through estrogen receptor alpha
SO NEUROPHARMACOLOGY
LA English
DT Article
DE Behavior; Cocaine; Dopamine; Estradiol; Mice; Ovariectomy
ID CONDITIONED PLACE PREFERENCE; STRIATAL DOPAMINE RELEASE; TANDEM
MASS-SPECTROMETRY; SELF-ADMINISTER COCAINE; VENTRAL TEGMENTAL AREA;
LONG-TERM ESTROGEN; SEX-DIFFERENCES; ER-BETA; OVARIAN HORMONES;
MESSENGER-RNA
AB Psychostimulant effects are enhanced by ovarian hormones in women and female rodents. Estradiol increases behavioral responses to psychostimulants in women and female rats, although the underlying mechanism is unknown. This study utilized mice to investigate the time frame and receptor mediation of estradiol's enhancement of cocaine-induced behavior as mice enable parallel use of genetic, surgical and pharmacological methods. The spontaneous behavior of Sham and Ovariectomized (Ovx) female wildtype (WT) mice was determined during habituation to a novel environment and after cocaine administration. Ovx mice were replaced with vehicle (sesame oil) or 17 beta-estradiol (E2) for 2 days or 30 min prior to a cocaine challenge to investigate the time course of E2's effects. To examine receptor mediation of estradiol effects, Ovx mice replaced for 2 days with either the ER alpha-selective agonist PPT or the ER beta-selective agonist DPN - were compared to Sham mice, and mice lacking either ER alpha (alpha ERKO) or ER beta (beta ERKO) were compared to WT littermates. Ovx mice exhibited fewer ambulations during habituation than Sham females. Cocaine-induced increases in behavioral ratings were greater in Sham than in Ovx mice. Two days but not 30 min of E2 replacement in Ovx mice increased cocaine responses to Sham levels. PPT replacement also increased the cocaine response relative to vehicle- or DPN- treated Ovx mice. alpha ERKO mice displayed modestly attenuated behavioral responses to novelty and cocaine compared to alpha WT littermates, but no behavioral differences were found between beta ERKO and beta WT mice. These results suggest that E2 enhances cocaine-stimulated locomotion in mice predominantly through ER alpha. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Van Swearingen, Amanda E. D.; Sanchez, Cristina L.; Frisbee, Suzanne M.; Williams, Antonia; Walker, Q. David; Kuhn, Cynthia M.] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA.
[Sanchez, Cristina L.] Rhein Westfal TH Aachen, Clin Child & Adolescent Psychiat Psychosomat & Ps, D-52074 Aachen, Nordrhein Westf, Germany.
[Korach, Kenneth S.] NIEHS, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA.
RP Kuhn, CM (reprint author), Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Room 100-B,Res Pk Bldg 2,POB 3813, Durham, NC 27710 USA.
EM aedvs@email.unc.edu; cristina.sanchez@duke.edu;
suzannefrisbee@alumni.ecu.edu; antonia.williams@yahoo.com;
qdwalker@duke.edu; korach@niehs.nih.gov; ckuhn@duke.edu
OI Sanchez, Cristina L./0000-0001-6380-4282; Korach,
Kenneth/0000-0002-7765-418X
FU NIDA [N01DA-9-7767, DA009079]; Division of Intramural Research of the
NIEHS [Z01ES70065]
FX The authors thank the laboratory of Dr. David Moody at the Center for
Human Toxicology, University of Utah for the assessment of COC
concentrations through NIDA Contract N01DA-9-7767. This work was
supported by NIDA grant #DA009079 to CMK. Support was provided by the
Division of Intramural Research of the NIEHS to KSK Z01ES70065. All
experiments in this study comply with all applicable current laws in the
United States.
NR 103
TC 5
Z9 5
U1 0
U2 12
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD SEP
PY 2013
VL 72
BP 236
EP 249
DI 10.1016/j.neuropharm.2013.04.015
PG 14
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 185CC
UT WOS:000321941800026
PM 23608737
ER
PT J
AU Duan, Q
van Gelderen, P
Duyn, J
AF Duan, Qi
van Gelderen, Peter
Duyn, Jeff
TI Improved Bloch-Siegert based B-1 mapping by reducing off-resonance shift
SO NMR IN BIOMEDICINE
LA English
DT Article
DE high field MRI; flip angle; wavelength effects; B-1 mapping; transmit
sense
AB An MRI method based on the Bloch-Siegert (BS) shift phenomenon was recently proposed as a fast and precise way to map a radio frequency (RF) transmit field (B-1(+) field). For MRI at high field, the mapping sensitivity of this approach was limited by tissue heating associated with a BS irradiation pulse. To mitigate this, we investigated the possibility of lowering the off-resonance frequency of this pulse since theoretical analysis indicated that the sensitivity of Bloch-Siegert based B-1(+) mapping could be substantially improved when irradiating closer to resonance. Using optimized irradiation pulse shape and gradient crushers to minimize direct excitation effects, in vivo experiments on human brains at 7T confirmed improved sensitivity with this approach. Improved sensitivity translated into an 80% reduction in B-1(+) estimation errors without increasing tissue heating. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.
C1 [Duan, Qi; van Gelderen, Peter; Duyn, Jeff] NINDS, Adv MRI Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
RP Duan, Q (reprint author), 10 Ctr Dr,Room B1D728,Bldg 10, Bethesda, MD 20892 USA.
EM Qi.Duan@nih.gov
RI Duan, Qi/J-7916-2016
OI Duan, Qi/0000-0002-2407-6611
FU National Institute of Neurological Disorders and Stroke
FX This research was supported by the Intramural Research Program of the
National Institute of Neurological Disorders and Stroke. The authors
would also like to thank Dr. Sacolick for providing the original Fermi
pulse used in (5) and the reviewers of this and related studies
submitted by our group for their constructive comments.
NR 24
TC 10
Z9 10
U1 2
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0952-3480
J9 NMR BIOMED
JI NMR Biomed.
PD SEP
PY 2013
VL 26
IS 9
BP 1070
EP 1078
DI 10.1002/nbm.2920
PG 9
WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
GA 200OO
UT WOS:000323078700003
PM 23355474
ER
PT J
AU Navarathna, DHMLP
Munasinghe, J
Lizak, MJ
Nayak, D
McGavern, DB
Roberts, DD
AF Navarathna, Dhammika H. M. L. P.
Munasinghe, Jeeva
Lizak, Martin J.
Nayak, Debasis
McGavern, Dorian B.
Roberts, David D.
TI MRI confirms loss of blood-brain barrier integrity in a mouse model of
disseminated candidiasis
SO NMR IN BIOMEDICINE
LA English
DT Article
DE Candida albicans; murine disseminated candidiasis; blood-brain barrier;
MRI; extracellular vascular contrast agent Gd-DTPA; ultrasmall iron
oxide particles; intravital two-photon microscopy
ID CENTRAL-NERVOUS-SYSTEM; IRON-OXIDE PARTICLES; USPIO-ENHANCED MR;
INFECTIOUS OSTEOMYELITIS; MACROPHAGE INFILTRATION; CELL RECRUITMENT;
VIRAL-INFECTION; IN-VITRO; ALBICANS; INFLAMMATION
AB Disseminated candidiasis primarily targets the kidneys and brain in mice and humans. Damage to these critical organs leads to the high mortality associated with such infections, and invasion across the blood-brain barrier can result in fungal meningoencephalitis. Candida albicans can penetrate a brain endothelial cell barrier in vitro through transcellular migration, but this mechanism has not been confirmed in vivo. MRI using the extracellular vascular contrast agent gadolinium diethylenetriaminepentaacetic acid demonstrated that integrity of the blood-brain barrier is lost during C. albicans invasion. Intravital two-photon laser scanning microscopy was used to provide the first real-time demonstration of C. albicans colonizing the living brain, where both yeast and filamentous forms of the pathogen were found. Furthermore, we adapted a previously described method utilizing MRI to monitor inflammatory cell recruitment into infected tissues in mice. Macrophages and other phagocytes were visualized in kidney and brain by the administration of ultrasmall iron oxide particles. In addition to obtaining new insights into the passage of C. albicans across the brain microvasculature, these imaging methods provide useful tools to study further the pathogenesis of C. albicans infections, to define the roles of Candida virulence genes in kidney versus brain infection and to assess new therapeutic measures for drug development. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.
C1 [Navarathna, Dhammika H. M. L. P.; Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Munasinghe, Jeeva; Lizak, Martin J.; Nayak, Debasis; McGavern, Dorian B.] NINDS, NIH, Bethesda, MD 20892 USA.
RP Roberts, DD (reprint author), NIH, Bldg 10,Room 2A33,10 Ctr Dr, Bethesda, MD 20892 USA.
EM droberts@helix.nih.gov
RI Roberts, David/A-9699-2008;
OI Roberts, David/0000-0002-2481-2981; McGavern, Dorian/0000-0001-9568-545X
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research [Z01 SC 009173]; National Institute of Neurological
Disorders and Stroke
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research (DDR, Z01 SC 009173) and National Institute of
Neurological Disorders and Stroke (MJL, DBM).
NR 54
TC 8
Z9 8
U1 1
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0952-3480
J9 NMR BIOMED
JI NMR Biomed.
PD SEP
PY 2013
VL 26
IS 9
BP 1125
EP 1134
DI 10.1002/nbm.2926
PG 10
WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
GA 200OO
UT WOS:000323078700009
PM 23606437
ER
PT J
AU Blomberg, BA
Akers, SR
Saboury, B
Mehta, NN
Cheng, G
Torigian, DA
Lim, E
Del Bello, C
Werner, TJ
Alavi, A
AF Blomberg, Bjoern A.
Akers, Scott R.
Saboury, Babak
Mehta, Nehal N.
Cheng, Gang
Torigian, Drew A.
Lim, Esther
Del Bello, Catherine
Werner, Thomas J.
Alavi, Abass
TI Delayed time-point F-18-FDG PET CT imaging enhances assessment of
atherosclerotic plaque inflammation
SO NUCLEAR MEDICINE COMMUNICATIONS
LA English
DT Article
DE atherosclerosis; fluorine-18 fluorodeoxyglucose; multiple time-point
imaging; positron emission tomography
ID POSITRON-EMISSION-TOMOGRAPHY; VASCULAR INFLAMMATION; FLUORODEOXYGLUCOSE
UPTAKE; LARGE ARTERIES; FDG-PET; RISK; RESOLUTION; WALL
AB Objective The aim of this study was to determine the ideal circulation time of fluorine-18 fluorodeoxyglucose (F-18-FDG) in order to detect and quantify atherosclerotic plaque inflammation with PET computed tomography (CT) imaging.Methods Fifteen patients underwent multiple time-point imaging at approximate to 60, 120, and 180 min after F-18-FDG administration. For each time point, global assessment of aortic and carotid F-18-FDG uptake was determined qualitatively by visual assessment and semiquantitatively by calculation of the mean and maximum standardized uptake values (SUV) and the corresponding target-to-background ratio (TBR).Results Delayed imaging achieved significant improvement in visualization of atherosclerotic plaque inflammation [Friedman's (2) statistic (d.f.=2, n=15)=24.13, P<0.001, Kendall's W=0.80]. This observation was confirmed by semiquantitative image analysis. At 1 h, the aortic and carotid SUVmean-calculated TBR was 1.05 [95% confidence interval (CI)=0.98, 1.11] and 0.88 (95% CI=0.81, 0.96), respectively. At 3 h, the TBR significantly increased to 1.57 (95% CI=1.28, 1.86; P=0.001) for the aorta and to 1.61 (95% CI=1.36, 1.87; P<0.001) for the carotid arteries. SUVmax-calculated TBRs showed a similar increase over time.Conclusion One- and 2-h F-18-FDG PET CT imaging is suboptimal for global assessment of atherosclerotic plaque inflammation compared with imaging at 3 h. Our data support the utilization of 3-h delayed imaging to obtain optimal data for the detection and quantification of atherosclerotic plaque inflammation in human arteries.
C1 [Blomberg, Bjoern A.; Saboury, Babak; Torigian, Drew A.; Alavi, Abass] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Blomberg, Bjoern A.; Saboury, Babak; Torigian, Drew A.; Werner, Thomas J.; Alavi, Abass] Hosp Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA.
[Akers, Scott R.; Cheng, Gang; Lim, Esther; Del Bello, Catherine] Philadelphia VA Med Ctr, Dept Radiol, Philadelphia, PA USA.
[Mehta, Nehal N.] NHLBI, Bethesda, MD 20892 USA.
[Blomberg, Bjoern A.] Univ Utrecht, Sch Med, Univ Med Ctr Utrecht, Utrecht, Netherlands.
RP Alavi, A (reprint author), 3400 Spruce St, Philadelphia, PA 19104 USA.
EM abass.alavi@uphs.upenn.edu
FU United States Department of Veterans Affairs (VISN 4 CPPF Grant)
FX This study was supported in part by a grant from the United States
Department of Veterans Affairs (VISN 4 CPPF Grant).
NR 29
TC 11
Z9 12
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0143-3636
J9 NUCL MED COMMUN
JI Nucl. Med. Commun.
PD SEP
PY 2013
VL 34
IS 9
BP 860
EP 867
DI 10.1097/MNM.0b013e3283637512
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 202QA
UT WOS:000323232000004
PM 23799532
ER
PT J
AU Akintoye, SO
Boyce, AM
Collins, MT
AF Akintoye, Sunday O.
Boyce, Alison M.
Collins, Michael T.
TI Dental perspectives in fibrous dysplasia and McCune-Albright syndrome
SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY
LA English
DT Article
ID STIMULATORY G-PROTEIN; GS-ALPHA GENE; ACTIVATING MUTATIONS; SKELETAL
PROGENITORS; BONE; OSTEOSARCOMA; MANAGEMENT; ENDOCRINE; SURGERY; LESIONS
AB McCune-Albright syndrome (MAS) is a rare multisystem disorder characterized by the triad of polyostotic fibrous dysplasia (FD), endocrine disorders, and cafe-au-lait skin pigmentation. Ninety percent of MAS patients have FD lesions in the craniofacial area, resulting in significant orofacial deformity, dental disorders, bone pain, and compromised oral health. Maxillomandibular FD is also associated with dental developmental disorders, malocclusion, and high caries index. There are limited data on the outcomes of dental treatments in maxillomandibular FD/MAS patients, because clinicians and researchers have limited access to patients, and there are concerns that dental surgery may activate quiescent jaw FD lesions to grow aggressively. This report highlights current perspectives on dental management issues associated with maxillomandibular FD within the context of MAS.
C1 [Akintoye, Sunday O.] Univ Penn, Sch Dent Med, Dept Oral Med, Philadelphia, PA 19104 USA.
[Boyce, Alison M.] Childrens Natl Med Ctr, Bone Hlth Program, Div Orthopaed & Sports Med, Washington, DC 20010 USA.
[Boyce, Alison M.] Childrens Natl Med Ctr, Div Endocrinol & Diabet, Washington, DC 20010 USA.
[Collins, Michael T.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA.
RP Akintoye, SO (reprint author), Univ Penn, Sch Dent Med, Dept Oral Med, Robert Schattner Room 211,240 South 40th St, Philadelphia, PA 19104 USA.
EM akintoye@dental.upenn.edu
FU National Institutes of Health/United States Department of Health and
Human Services (NIH/DHHS), Bethesda, MD; National Institute of Dental
and Craniofacial Research (NIDCR) [R21DE022826]; National Cancer
Institute (NCI) [K22CA169089]; Division of Intramural Research NIDCR, a
part of the Intramural Research Program of NIH/DHHS; Bone Health Program
at Children's National Medical Center, Washington DC
FX This work was supported in part by National Institutes of Health/United
States Department of Health and Human Services (NIH/DHHS), Bethesda, MD,
grant R21DE022826 from the National Institute of Dental and Craniofacial
Research (NIDCR), and grant K22CA169089 from the National Cancer
Institute (NCI) (S.O.A.); the Division of Intramural Research NIDCR, a
part of the Intramural Research Program of NIH/DHHS (M.T.C. and A.M.B.);
and the Bone Health Program at Children's National Medical Center,
Washington DC (A.M.B.).
NR 44
TC 6
Z9 6
U1 2
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 2212-4403
EI 1528-395X
J9 OR SURG OR MED OR PA
JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol.
PD SEP
PY 2013
VL 116
IS 3
BP E149
EP E155
DI 10.1016/j.oooo.2013.05.023
PG 7
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 205ZM
UT WOS:000323484300001
PM 23953425
ER
PT J
AU Shahzad, M
Sivakumaran, TA
Qaiser, TA
Schultz, JM
Hussain, Z
Flanagan, M
Bhinder, MA
Kissell, D
Greinwald, JH
Khan, SN
Friedman, TB
Zhang, KJ
Riazuddin, S
Riazuddin, S
Ahmed, ZM
AF Shahzad, Mohsin
Sivakumaran, Theru A.
Qaiser, Tanveer A.
Schultz, Julie M.
Hussain, Zawar
Flanagan, Megan
Bhinder, Munir A.
Kissell, Diane
Greinwald, John H., Jr.
Khan, Shaheen N.
Friedman, Thomas B.
Zhang, Kejian
Riazuddin, Saima
Riazuddin, Sheikh
Ahmed, Zubair M.
TI Genetic Analysis through OtoSeq of Pakistani Families Segregating
Prelingual Hearing Loss
SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY
LA English
DT Article
DE hearing loss; Usher syndrome; microdroplet PCR; next-generation
sequencing; clinical diagnosis; genetic etiology; PDS; MYO7A; CDH23
ID SYNDROME TYPE-I; MYOSIN VIIA GENE; USHER-SYNDROME; NONSYNDROMIC
DEAFNESS; MUTATION SPECTRUM; GENOMIC CAPTURE; DIVERSE ORIGINS; CDH23;
HETEROGENEITY; GENERATION
AB Objective
To identify the genetic cause of prelingual sensorineural hearing loss in Pakistani families using a next-generation sequencing (NGS)-based mutation screening test named OtoSeq.
Study Design
Prospective study.
Setting
Research laboratory.
Subjects and Methods
We used 3 fluorescently labeled short tandem repeat (STR) markers for each of the known autosomal recessive nonsyndromic (DFNB) and Usher syndrome (USH) locus to perform a linkage analysis of 243 multigenerational Pakistani families segregating prelingual hearing loss. After genotyping, we focused on 34 families with potential linkage to MYO7A, CDH23, and SLC26A4. We screened affected individuals from a subset of these families using the OtoSeq platform to identify underlying genetic variants. Sanger sequencing was performed to confirm and study the segregation of mutations in other family members. For novel mutations, normal hearing individuals from ethnically matched backgrounds were also tested.
Results
Hearing loss was found to co-segregate with locus-specific STR markers for MYO7A in 32 families, CDH23 in 1 family, and SLC26A4 in 1 family. Using the OtoSeq platform, a microdroplet PCR-based enrichment followed by NGS, we identified mutations in 28 of the 34 families including 11 novel mutations. Sanger sequencing of these mutations showed 100% concordance with NGS data and co-segregation of the mutant alleles with the hearing loss phenotype in the respective families.
Conclusion
Using NGS-based platforms like OtoSeq in families segregating hearing loss will contribute to the identification of common and population-specific mutations, early diagnosis, genetic counseling, and molecular epidemiology.
C1 [Shahzad, Mohsin; Riazuddin, Saima; Ahmed, Zubair M.] Cincinnati Childrens Hosp Res Fdn, Div Ophthalmol, Cincinnati, OH USA.
[Sivakumaran, Theru A.; Flanagan, Megan; Kissell, Diane; Greinwald, John H., Jr.; Zhang, Kejian; Riazuddin, Saima; Ahmed, Zubair M.] Cincinnati Childrens Hosp Res Fdn, Human Genet, Cincinnati, OH USA.
[Sivakumaran, Theru A.; Zhang, Kejian] Univ Cincinnati, Dept Pediat, Cincinnati, OH 45221 USA.
[Qaiser, Tanveer A.; Hussain, Zawar; Bhinder, Munir A.; Khan, Shaheen N.; Riazuddin, Saima; Ahmed, Zubair M.] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan.
[Schultz, Julie M.; Friedman, Thomas B.] NIDCD, Mol Genet Lab, NIH, Bethesda, MD USA.
[Greinwald, John H., Jr.] Cincinnati Childrens Hosp Res Fdn, Cincinnati, OH USA.
[Riazuddin, Sheikh] Univ Hlth Sci, Allama Iqbal Med Coll, Lahore, Pakistan.
[Riazuddin, Sheikh] Univ Lahore, Lahore, Pakistan.
RP Ahmed, ZM (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Pediat Ophthalmol, 3333 Burnet Ave,MLC 7003, Cincinnati, OH 45229 USA.
EM zubair.ahmed@cchmc.org
RI Nasim Khan, Shaheen/F-2135-2015
FU Intramural funds NIDCD [DC000039-15]; NIDCD/NIH [R01 DC011803, R01
DC012564]; RPB Foundation
FX Intramural funds NIDCD DC000039-15 to Thomas B. Friedman. NIDCD/NIH
research grant R01 DC011803 to Saima Riazuddin. Career Development Award
from RPB Foundation to Zubair M. Ahmed. NIDCD/NIH research grant R01
DC012564 to Zubair M. Ahmed.
NR 63
TC 9
Z9 9
U1 0
U2 5
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0194-5998
J9 OTOLARYNG HEAD NECK
JI Otolaryngol. Head Neck Surg.
PD SEP
PY 2013
VL 149
IS 3
BP 478
EP 487
DI 10.1177/0194599813493075
PG 10
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 206BA
UT WOS:000323489500021
PM 23770805
ER
PT J
AU Harry, GJ
AF Harry, G. Jean
TI Microglia during development and aging
SO PHARMACOLOGY & THERAPEUTICS
LA English
DT Review
DE Microglia; P2X receptors; Aging; Development; Synapse stripping
ID CENTRAL-NERVOUS-SYSTEM; TOLL-LIKE RECEPTORS; FOCAL CEREBRAL-ISCHEMIA;
HUMAN ADULT MICROGLIA; TUMOR-NECROSIS-FACTOR; GLYCOSYLATION
END-PRODUCTS; PURINERGIC P2X(7) RECEPTOR; DEVELOPING RAT-BRAIN; GLIAL
TNF-ALPHA; ALZHEIMERS-DISEASE
AB Microglia are critical nervous system-specific cells influencing brain development, maintenance of the neural environment, response to injury, and repair. They contribute to neuronal proliferation and differentiation, pruning of dying neurons, synaptic remodeling and clearance of debris and aberrant proteins. Colonization of the brain occurs during gestation with an expansion following birth with localization stimulated by programmed neuronal death, synaptic pruning, and axonal degeneration. Changes in microglia phenotype relate to cellular processes including specific neurotransmitter, pattern recognition, or immune-related receptor activation. Upon activation, microglia cells have the capacity to release a number of substances, e.g., cytokines, chemokines, nitric oxide, and reactive oxygen species, which could be detrimental or beneficial to the surrounding cells. With aging, microglia shift their morphology and may display diminished capacity for normal functions related to migration, clearance, and the ability to shift from a pro-inflammatory to an anti-inflammatory state to regulate injury and repair. This shift in microglia potentially contributes to increased susceptibility and neurodegeneration as a function of age. In the current review, information is provided on the colonization of the brain by microglia, the expression of various pattern recognition receptors to regulate migration and phagocytosis, and the shift in related functions that occur in normal aging. Published by Elsevier Inc.
C1 NIEHS, Natl Toxicol Program Lab, Res Triangle Pk, NC 27709 USA.
RP Harry, GJ (reprint author), NIEHS, Natl Toxicol Program Lab, MD C1-04,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM harry@niehs.nih.gov
FU National Toxicology Program Division; National Institute of
Environmental Health Sciences; National Institutes of Health; Department
of Health and Human Services [1Z01ES101623, ES021164]
FX This research was supported by the National Toxicology Program Division,
the National Institute of Environmental Health Sciences, the National
Institutes of Health, and the Department of Health and Human Services
#1Z01ES101623 and ES021164. The views expressed in this article are
those of the author and they do not necessarily represent the views or
policies of the National Toxicology Program.
NR 286
TC 88
Z9 92
U1 8
U2 68
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0163-7258
J9 PHARMACOL THERAPEUT
JI Pharmacol. Ther.
PD SEP
PY 2013
VL 139
IS 3
BP 313
EP 326
DI 10.1016/j.pharmthera.2013.04.013
PG 14
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 204VH
UT WOS:000323398900002
PM 23644076
ER
PT J
AU De Luca, P
Moiola, CP
Zalazar, F
Gardner, K
Vazquez, ES
De Siervi, A
AF De Luca, P.
Moiola, C. P.
Zalazar, F.
Gardner, K.
Vazquez, E. S.
De Siervi, A.
TI BRCA1 and p53 regulate critical prostate cancer pathways
SO PROSTATE CANCER AND PROSTATIC DISEASES
LA English
DT Article
DE BRCA1; p53; GADD153; DNA damage
ID E-CADHERIN; TUMOR PROGRESSION; BREAST-CANCER; CELL-LINES; GENE;
CARCINOMAS; EXPRESSION; HEDGEHOG; SUSCEPTIBILITY; TRANSCRIPTION
AB BACKGROUND: Loss or mutations of the BRCA1 gene are associated with increased risk of breast and ovarian cancers and with prostate cancer (PCa) aggressiveness. Previously, we identified GADD153 as a target of BRCA1 protein, which increases doxorubicin sensitivity in human p53 -/- PCa cells (PC3). Considering that p53 is a crucial target in cancer therapy, in this work we investigated p53 role in the regulation of transcription of GADD153.
METHODS: We performed reverse transcription quantitative PCR (RT-qPCR), western blot and luciferase assays to analyze GADD153 and/or BRCA1 expression in response to ultraviolet or doxorubicin exposure in PC3 p53 stable-transfected cells and LNCaP (p53 +/+) cells. BRCA1 protein recruitment to GADD153 promoter was studied by chromatin immunoprecipitation-qPCR. To assess expression of BRCA1 and/or p53 target genes, we used a panel of stable-transfected PCa cell lines. We finally analyzed these genes in vivo using BRCA1-depleted PCa xenograft models.
RESULTS: We found that GADD153 was highly induced by doxorubicin in PC3 cells; however, this response was totally abolished in LNCaP (p53wt) and in p53-restituted PC3 cells. Furthermore, BRCA1 protein associates to GADD153 promoter after DNA damage in the presence of p53. Additionally, we demonstrated that BRCA1 and/or p53 modulate genes involved in DNA damage and cell cycle regulation (cyclin D1, BLM, BRCA2, DDB2, p21(WAF1/CIP1), H3F3B, GADD153, GADD45A, FEN1, CCNB2), EMT (E-cadherin, beta-catenin, vimentin, fibronectin, slug, snail) and Hedgehog pathways (SHH, IHH, DHH, Gli1, PATCH1). Furthermore, xenograft studies demonstrated that BRCA1 knockdown in PC3 cells increased tumor growth and modulated these genes in vivo.
CONCLUSIONS: Although BRCA1 induces GADD153 in a p53 independent manner, p53 abolished GADD153 induction in response to DNA damage. In addition, several important PCa targets are modulated by BRCA1 and p53. Altogether, these data might be important to understand the therapy response of PCa patients.
C1 [De Luca, P.; Moiola, C. P.; Zalazar, F.; Vazquez, E. S.; De Siervi, A.] Univ Buenos Aires, CONICET, IQUIBICEN, Dept Biol Chem,Sch Sci FCEN, Buenos Aires, DF, Argentina.
[Gardner, K.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
RP De Siervi, A (reprint author), Univ Buenos Aires, CONICET, IQUIBICEN, Dept Biol Chem,Sch Sci FCEN, C1428EGA, Buenos Aires, DF, Argentina.
EM adesiervi@qb.fcen.uba.ar
FU Argentinean Agency of Science and Technology (ANPCyT) [PICT 2006-00228,
PICT 2006-00367, PICT 2010-00431]; CONICET; NCI, NIH (USA)
FX This research was supported by the Argentinean Agency of Science and
Technology (ANPCyT PICT 2006-00228, PICT 2006-00367 and PICT
2010-00431). E. Vazquez and A. De Siervi are members of the career of
scientific researcher at the National Research Council (CONICET). P De
Luca holds postdoctoral fellowship from CONICET. C Moiola and F Zalazar
hold PhD scholarships from CONICET. K. Gardner is a principal
investigator at the NCI, NIH (USA).
NR 31
TC 11
Z9 12
U1 0
U2 17
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1365-7852
J9 PROSTATE CANCER P D
JI Prostate Cancer Prostatic Dis.
PD SEP
PY 2013
VL 16
IS 3
BP 233
EP 238
DI 10.1038/pcan.2013.12
PG 6
WC Oncology; Urology & Nephrology
SC Oncology; Urology & Nephrology
GA 201NK
UT WOS:000323148100003
PM 23670255
ER
PT J
AU Forsythe, LP
Rowland, JH
Padgett, L
Blaseg, K
Siegel, SD
Dingman, CM
Gillis, TA
AF Forsythe, Laura P.
Rowland, Julia H.
Padgett, Lynne
Blaseg, Karyl
Siegel, Scott D.
Dingman, Chad M.
Gillis, Theresa A.
TI The cancer psychosocial care matrix: a community-derived evaluative tool
for designing quality psychosocial cancer care delivery
SO PSYCHO-ONCOLOGY
LA English
DT Article
DE psychosocial; care delivery; cancer; survivorship
ID CLINICAL-PRACTICE GUIDELINES; DISEASE PROGRESSION; ONCOLOGY SETTINGS;
ROUTINE CANCER; DEPRESSION; PHYSICIANS; DISTRESS; BREAST; METAANALYSIS;
PERFORMANCE
AB Objective Although the Institute of Medicine provided a vision for effective psychosocial care for cancer survivors, limited guidance exists regarding the essential components of comprehensive care or progressive steps for implementing each component. This paper describes the development of a unique tool for assessing capacity to provide quality psychosocial care to cancer survivors and the results of the first implementation of this tool in community settings. Methods The psychosocial working group of the National Cancer Institute Community Cancer Centers Program (NCCCP) developed the Cancer Psychosocial Care Matrix assessment tool. All NCCCP sites (n=30, enrolled in 2007 and 2010) completed the matrix indicating their capacity for providing psychosocial care at entry into NCCCP (baseline') after 2years of NCCCP participation (2007 sites only) and within the coming year (future aspirations'). Results At baseline, matrix responses reflected few or no systematic processes in place for most components of comprehensive psychosocial care. However, reported capacity to deliver specific components improved at 2years post-NCCCP entry for the 2007 sites and in all NCCCP sites' future aspirations. Conclusions With growing demand on cancer centers to meet new metrics of quality care, the psychosocial matrix can help centers systematically identify and develop steps to address gap areas in their capacity to meet these new standards. The Cancer Psychosocial Care Matrix appears to enable evaluation of psychosocial programs, may promote intentions to improve psychosocial services, and can facilitate communication of best practices' among cancer centers. Copyright (c) 2013 John Wiley & Sons, Ltd.
C1 [Forsythe, Laura P.; Rowland, Julia H.; Padgett, Lynne] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, NIH,DHHS, Rockville, MD USA.
[Forsythe, Laura P.] NCI, Canc Prevent Fellowship Program, Ctr Canc Training, NIH,DHHS, Rockville, MD USA.
[Forsythe, Laura P.] Patient Ctr Outcomes Res Inst, Washington, DC 20036 USA.
[Blaseg, Karyl] Billings Clin Canc Ctr, Billings, MT USA.
[Siegel, Scott D.; Gillis, Theresa A.] Christiana Care Hlth Syst, Helen F Graham Canc Ctr, Newark, DE USA.
[Dingman, Chad M.] Spartanburg Reg Healthcare Syst, Gibbs Canc Ctr, Spartanburg, SC USA.
RP Forsythe, LP (reprint author), Patient Ctr Outcomes Res Inst, 1828 L St NW, Washington, DC 20036 USA.
EM lforsythe@pcori.org
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
Contract No. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the US government. The
authors gratefully acknowledge the contributions of the psychosocial
matrix working group: Karyl Blaseg, Chad M. Dingman, Theresa Gillis,
Margaret Palmer, Julia H. Rowland, Scott D. Siegel, and Amber
Ussin-Davey. We also gratefully acknowledge the efforts of all 30 NCCCP
sites, including the 16 sites enrolled in 2007: Ascension-Seton (TX),
Ascension-Columbia St. Mary's (WI), Ascension-St. Vincent (IN), Billings
Clinic (MT), CHI-Penrose Cancer Center (CO), CHI-Good Samaritan (NE),
CHI-St. Elizabeth (NE), CHI-St. Francis (NE), CHI-St. Joseph (MD),
Christiana Care (DE), Hartford Hospital (CT), Our Lady of the Lake (LA),
Sanford Hospital (SD), Spartanburg Regional Hospital (SC), St. Joseph
Orange (CA), and St. Joseph's Candler (GA); and the 14 sites enrolled in
2010: Einstein Medical Center (PA), Geisinger Medical Center (PA),
Gundersen Lutheran (WI), Lehigh Valley Hospital (PA), Maine Medical
Center (ME), Mercy Medical Center (IA), Northside Hospital (GA), Norton
Suburban Hospital (KY), Providence Portland Medical Center (OR), Saint
Mary's Healthcare (MI), St. Joseph Mercy Hospital (MI), St. Luke's
Regional Medical Center (IA), Queen's Medical Center (HI), and Waukesha
Memorial Hospital (WI). Finally, we especially thank the NCCCP principal
investigators for their commitment to this component of their contract
and the representatives from each NCCCP site to the Survivorship and
Palliative Care Committee.
NR 49
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Z9 7
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1057-9249
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD SEP
PY 2013
VL 22
IS 9
BP 1953
EP 1962
DI 10.1002/pon.3254
PG 10
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA 205NQ
UT WOS:000323451500004
PM 23436558
ER
PT J
AU Jones, P
Blunda, M
Biegel, G
Carlson, LE
Biel, M
Wiener, L
AF Jones, Paul
Blunda, Megan
Biegel, Gina
Carlson, Linda E.
Biel, Matthew
Wiener, Lori
TI Can mindfulness-based interventions help adolescents with cancer?
SO PSYCHO-ONCOLOGY
LA English
DT Article
DE mindfulness; adolescents; cancer; mind-body interventions
ID CHILDREN; TRIAL
AB During the past 30years, there has been an increase in the incidence of cancer in adolescents. While recent studies have illustrated remarkable resilience in youth living with cancer, they can also face daunting acute and chronic adjustment struggles, cognitive and school problems, family and peer relational difficulties, depression, post-traumatic stress symptoms, and other anxiety disorders. Mindfulness-based interventions (MBIs), increasingly shown to be effective in a variety of medical and mental health settings, may be particularly beneficial for adolescents with cancer. This paper reviews evidence from clinical trials of MBIs showing a variety of benefits for adult cancer patients, adolescents with anxiety disorders and chronic pain, and clinically healthy teenagers, which collectively point to likely benefits of MBIs for teen cancer patients. The authors also explore ways that the particular psychological problems often faced by teen cancer patients, including anxiety about the future, may be especially well suited to mindfulness approaches such as learning to observe physical sensations, thoughts, and emotions, as well as cultivating compassion towards themselves and others. The paper concludes with an exploration of unanswered and potential research questions regarding the future use of MBIs with adolescents with cancer, and potentially with teenagers with other chronic diseases. Copyright (c) 2013 John Wiley & Sons, Ltd.
C1 [Jones, Paul; Blunda, Megan; Biegel, Gina; Carlson, Linda E.; Biel, Matthew; Wiener, Lori] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Wiener, L (reprint author), NCI, Ctr Canc Res, Pediat Clin I SE, 10 Ctr Dr,Bldg 10,Room 1-6466, Bethesda, MD 20892 USA.
EM wienerl@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX This work is supported in part by the intramural Research Programs of
the NIH, National Cancer Institute, Center for Cancer Research
NR 19
TC 8
Z9 8
U1 3
U2 35
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1057-9249
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD SEP
PY 2013
VL 22
IS 9
BP 2148
EP 2151
DI 10.1002/pon.3251
PG 4
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA 205NQ
UT WOS:000323451500030
PM 23417883
ER
PT J
AU Bindewald, E
Shapiro, BA
AF Bindewald, Eckart
Shapiro, Bruce A.
TI Computational detection of abundant long-range nucleotide covariation in
Drosophila genomes
SO RNA-A PUBLICATION OF THE RNA SOCIETY
LA English
DT Article
DE Drosophila; RNA-RNA; covariation; interaction network; long-range
interactions
ID RNA-RNA INTERACTION; LARGE GENE LISTS; SECONDARY STRUCTURE PREDICTION;
BASE-PAIRING PROBABILITIES; SEQUENCE ALIGNMENTS; SEMANTIC SIMILARITY;
PARTITION-FUNCTION; GO TERMS; TOOL; NANOPARTICLES
AB Functionally important nucleotide base-pairing often manifests itself in sequence alignments in the form of compensatory base changes (covariation). We developed a novel index-based computational method (CovaRNA) to detect long-range covariation on a genomic scale, as well as another computational method (CovStat) for determining the statistical significance of observed covariation patterns in alignment pairs. Here we present an all-versus-all search for nucleotide covariation in Drosophila genomic alignments. The search is genome wide, with the restriction that only alignments that correspond to euchromatic regions, which consist of at least 10 Drosophila species, are being considered (59% of the euchromatic genome of Drosophila melanogaster). We find that long-range covariations are especially prevalent between exons of mRNAs as well as noncoding RNAs; the majority of the observed covariations appear as not reverse complementary, but as synchronized mutations, which could be due to interactions with common interaction partners or due to the involvement of genomic elements that are antisense of annotated transcripts. The involved genes are enriched for functions related to regionalization as well as neural and developmental processes. These results are computational evidence that RNA-RNA long-range interactions are a widespread phenomenon that is of fundamental importance to a variety of cellular processes.
C1 [Bindewald, Eckart] SAIC Frederick Inc, Basic Sci Program, Ctr Canc Res, Nanobiol Program,Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Shapiro, Bruce A.] NCI, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA.
RP Shapiro, BA (reprint author), NCI, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA.
EM shapirbr@mail.nih.gov
FU Frederick National Laboratory for Cancer Research, National Institutes
of Health [HHSN261200800001E]; Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research
FX Computational support by the NCI Advanced Biomedical Computing Center
(ABCC) as well as the NIH Helix/Biowulf facility is highly appreciated.
This work has been funded in whole or in part with Federal funds from
the Frederick National Laboratory for Cancer Research, National
Institutes of Health, under Contract No. HHSN261200800001E. This
research was supported (in part) by the Intramural Research Program of
the NIH, National Cancer Institute, Center for Cancer Research. The
content of this publication does not necessarily reflect the views or
policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products, or organizations imply
endorsement by the US Government.
NR 55
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U1 1
U2 4
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1355-8382
J9 RNA
JI RNA-Publ. RNA Soc.
PD SEP
PY 2013
VL 19
IS 9
BP 1171
EP 1182
DI 10.1261/rna.037630.112
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 203UP
UT WOS:000323319600001
PM 23887147
ER
PT J
AU Malagon, F
AF Malagon, Francisco
TI RNase III is required for localization to the nucleoid of the 5 '
pre-rRNA leader and for optimal induction of rRNA synthesis in E. coli
SO RNA-A PUBLICATION OF THE RNA SOCIETY
LA English
DT Article
DE Pre-rRNA; RNase III; nucleoid; ribosomal operon; Fis
ID ESCHERICHIA-COLI; RIBONUCLEASE-III; QUALITY-CONTROL; BINDING-PROTEIN;
GENE-EXPRESSION; TRANSCRIPTION; DEGRADATION; CELLS; BIOGENESIS; BACTERIA
AB It has recently been demonstrated that ribosomes are preferentially localized outside the nucleoid in Escherichia coli, but little is known about the spatial regulation of pre-rRNA processing. In this work, I investigate the cellular distribution of leader pre-rRNAs using RNA-FISH. In contrast to mature rRNA, the 5' proximal leader region associates with the nucleoid, and this association occurs in an RNase III-dependent manner. Moreover, RNase III plays a role in the rapid induction of ribosomal operons during outgrowth and is essential in the absence of the transcriptional regulator Fis, suggesting a linkage of transcription and RNA processing for ribosomal operons in E. coli.
C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Malagon, F (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM malagonf@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research
FX I thank Sankar Adhya for his constant and generous scientific and
financial support and for critical comments on this manuscript. I also
thank Donald Court, Susan Gottesman, and Nadim Majdalani for strains and
plasmids; Donald Court, Brian Peddie, and Nadim Majdalani for comments;
and Cindy Clark, NIH Library Writing Center, for manuscript editing
assistance. This research was supported by the Intramural Research
Program of the National Institutes of Health, National Cancer Institute,
Center for Cancer Research.
NR 56
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U1 1
U2 3
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1355-8382
J9 RNA
JI RNA-Publ. RNA Soc.
PD SEP
PY 2013
VL 19
IS 9
BP 1200
EP 1207
DI 10.1261/rna.038588.113
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 203UP
UT WOS:000323319600004
PM 23893733
ER
PT J
AU Church, G
AF Church, George
TI Please Reanimate Reviving mammoths and other extinct creatures is a good
idea
SO SCIENTIFIC AMERICAN
LA English
DT Editorial Material
C1 [Church, George] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Church, George] NIH, Ctr Excellence Genom Sci Harvard, Bethesda, MD USA.
RP Church, G (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
NR 0
TC 3
Z9 3
U1 4
U2 21
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0036-8733
J9 SCI AM
JI Sci.Am.
PD SEP
PY 2013
VL 309
IS 3
BP 12
EP 12
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 205RC
UT WOS:000323461300011
PM 24003542
ER
PT J
AU Pinkerton, LE
Hein, MJ
Meyers, A
Kamel, F
AF Pinkerton, Lynne E.
Hein, Misty J.
Meyers, Alysha
Kamel, Freya
TI Assessment of ALS mortality in a cohort of formaldehyde-exposed garment
workers
SO AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
LA English
DT Article
ID AMYOTROPHIC-LATERAL-SCLEROSIS; SURVIVAL; UPDATE
C1 [Pinkerton, Lynne E.; Hein, Misty J.; Meyers, Alysha] NIOSH, Industrywide Studies Branch, Div Surveillance Hazard Evaluat & Field Studies, Cincinnati, OH 45226 USA.
[Kamel, Freya] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
RP Pinkerton, LE (reprint author), NIOSH, Industrywide Studies Branch, Div Surveillance Hazard Evaluat & Field Studies, 4676 Columbia Pkwy,R-15, Cincinnati, OH 45226 USA.
EM lep5@cdc.gov
OI Meyers, Alysha/0000-0002-6402-0145; Kamel, Freya/0000-0001-5052-6615
FU Intramural Research Program of the National Institute for Occupational
Safety and Health; Intramural Research Program of the National
Institutes of Health, National Institute of Environmental Health
Sciences
FX This work was supported in part by the Intramural Research Program of
the National Institute for Occupational Safety and Health and in part by
the Intramural Research Program of the National Institutes of Health,
National Institute of Environmental Health Sciences.
NR 14
TC 6
Z9 6
U1 0
U2 6
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 2167-8421
J9 AMYOTROPH LA SCL FR
JI Amyotroph. Lateral Scher. Frontotemp. Degenerat.
PD SEP
PY 2013
VL 14
IS 5-6
BP 353
EP 355
DI 10.3109/21678421.2013.778284
PG 3
WC Clinical Neurology
SC Neurosciences & Neurology
GA 196NR
UT WOS:000322782800005
PM 23570513
ER
PT J
AU Fondell, E
O'Reilly, EJ
Fitzgerald, KC
Falcone, GJ
McCullough, ML
Park, Y
Kolonel, LN
Ascherio, A
AF Fondell, Elinor
O'Reilly, Eilis J.
Fitzgerald, Kathryn C.
Falcone, Guido J.
McCullough, Marjorie L.
Park, Yikyung
Kolonel, Laurence N.
Ascherio, Alberto
TI Magnesium intake and risk of amyotrophic lateral sclerosis: Results from
five large cohort studies
SO AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
LA English
DT Article
DE Amyotrophic lateral sclerosis; motor neuron disease; longitudinal cohort
studies; epidemiology; magnesium
ID FOOD FREQUENCY QUESTIONNAIRE; SOCIETY CANCER PREVENTION; BASE-LINE
CHARACTERISTICS; DIETARY-INTAKE; DISEASE; DISORDERS; HEALTH;
PATHOGENESIS; ASSOCIATION; SURVIVAL
AB A low magnesium intake has been suggested to be associated with amyotrophic lateral sclerosis (ALS) in pathological and case-control studies, but prospective studies in humans are lacking.
The relation between dietary intake of magnesium and ALS risk was explored in five large prospective cohort studies (the Nurses' Health Study, the Health Professionals Follow-up Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort Study, and the National Institutes of Health-AARP Diet and Health Study), comprising over 1,050,000 males and females contributing 1093 cases of ALS during a mean of 15 years of follow-up. Cox proportional hazards models were used within each cohort, and cohort-specific estimates were subsequently pooled using a random-effects model. Results demonstrated that dietary magnesium intake was not associated with ALS risk, relative risk 1.07, 95% confidence interval 0.88-1.31 comparing the highest quintile of intake with the lowest. This finding does not support a protective effect of magnesium intake on ALS risk. Further analyses should explore magnesium intake in combination with heavy metal exposure and genetic variants affecting magnesium absorption.
C1 [Fondell, Elinor; O'Reilly, Eilis J.; Fitzgerald, Kathryn C.; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Falcone, Guido J.; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Falcone, Guido J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[McCullough, Marjorie L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Park, Yikyung] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Kolonel, Laurence N.] Univ Hawaii, Program Epidemiol, Ctr Canc, Honolulu, HI 96822 USA.
[Ascherio, Alberto] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
[Ascherio, Alberto] Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Fondell, E (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 655 Huntington Ave, Boston, MA 02115 USA.
EM efondell@hsph.harvard.edu
RI Falcone, Guido/L-2287-2016;
OI Falcone, Guido/0000-0002-6407-0302; Park, Yikyung/0000-0002-6281-489X
FU National Institute of Neurological Diseases and Stroke [RO1 NS045893];
National Cancer Institute [PO1 CA87969, PO1 CA055075]
FX This work was supported by a grant from the National Institute of
Neurological Diseases and Stroke (RO1 NS045893) and by grants from the
National Cancer Institute (PO1 CA87969 and PO1 CA055075).
NR 37
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U1 0
U2 6
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 2167-8421
J9 AMYOTROPH LA SCL FR
JI Amyotroph. Lateral Scher. Frontotemp. Degenerat.
PD SEP
PY 2013
VL 14
IS 5-6
BP 356
EP 361
DI 10.3109/21678421.2013.803577
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 196NR
UT WOS:000322782800006
PM 23777266
ER
PT J
AU Fang, F
Al-Chalabi, A
Ronnevi, LO
Turner, MR
Wirdefeldt, K
Kamel, F
Ye, WM
AF Fang, Fang
Al-Chalabi, Ammar
Ronnevi, Lars-Olof
Turner, Martin R.
Wirdefeldt, Karin
Kamel, Freya
Ye, Weimin
TI Amyotrophic lateral sclerosis and cancer: A register-based study in
Sweden
SO AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
LA English
DT Article
DE Amyotrophic lateral sclerosis; cancer; melanoma; odds ratio; relative
risk
ID MOTOR-NEURON DISEASE; PARKINSONS-DISEASE; PROSPECTIVE COHORT;
RISK-FACTOR; DIAGNOSIS; METAANALYSIS; SMOKING
AB Comorbidity of cancer with ALS has been studied previously. Detailed description of the temporal relationship between cancer and ALS is, however, lacking. We conducted a nested case-control study of ALS in Sweden during 1987-2009, including 5481 cases of ALS identified from the Swedish Patient Register and 27,405 controls randomly selected from the general Swedish population. Odds ratios (ORs) for association of ALS with previous cancer diagnosis and incidence rate ratios (IRRs) of cancer after diagnosis were calculated to compare ALS patients with ALS-free individuals. Overall, a previous cancer diagnosis was not associated with subsequent risk of ALS (OR 1.00; 95% CI 0.91-1.10). No overall association was observed for any specific cancer type. An increased risk of ALS was observed during the first year after cancer diagnosis (OR 1.50; 95% CI 1.17-1.92). In contrast, a lower risk of cancer was observed in ALS patients after diagnosis compared with ALS-free individuals (IRR 0.84; 95% CI 0.69-1.02). The risk reduction was seen primarily two or more years after ALS diagnosis (IRR 0.64; 95% CI 0.45-0.88). Our results provide no evidence for comorbidity of cancer and ALS overall. Surveillance biases seem the most likely explanation for the limited associations detected.
C1 [Fang, Fang; Wirdefeldt, Karin; Ye, Weimin] Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.
[Ronnevi, Lars-Olof; Wirdefeldt, Karin] Karolinska Inst, Dept Clin Neurosci, S-17177 Stockholm, Sweden.
[Al-Chalabi, Ammar] Kings Coll London, Inst Psychiat, MRC, Ctr Neurodegenerat Res, London, England.
[Turner, Martin R.] Univ Oxford, Nuffield Dept Clin Neurosci, Oxford, England.
[Kamel, Freya] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA.
RP Fang, F (reprint author), Karolinska Inst, Dept Med Epidemiol & Biostat, Box 281, S-17177 Stockholm, Sweden.
EM fang.fang@ki.se
RI Al-Chalabi, Ammar/E-5361-2010;
OI Al-Chalabi, Ammar/0000-0002-4924-7712; Fang, Fang/0000-0002-3310-6456;
Kamel, Freya/0000-0001-5052-6615; Turner, Martin/0000-0003-0267-3180
FU Swedish Research Council; Swedish Society for Medical Research
FX This study was supported by Swedish Research Council grants (F. F. and
W. Y.) and the Swedish Society for Medical Research (F. F.).
NR 26
TC 9
Z9 9
U1 0
U2 5
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 2167-8421
J9 AMYOTROPH LA SCL FR
JI Amyotroph. Lateral Scher. Frontotemp. Degenerat.
PD SEP
PY 2013
VL 14
IS 5-6
BP 362
EP 368
DI 10.3109/21678421.2013.775309
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 196NR
UT WOS:000322782800007
PM 23527497
ER
PT J
AU Myatt, L
Clifton, RG
Roberts, JM
Spong, CY
Wapner, RJ
Thorp, JM
Mercer, BM
Peaceman, AM
Ramin, SM
Carpenter, MW
Sciscione, A
Tolosa, JE
Saade, G
Sorokin, Y
Anderson, GD
AF Myatt, L.
Clifton, R. G.
Roberts, J. M.
Spong, C. Y.
Wapner, R. J.
Thorp, J. M., Jr.
Mercer, B. M.
Peaceman, A. M.
Ramin, S. M.
Carpenter, M. W.
Sciscione, A.
Tolosa, J. E.
Saade, G.
Sorokin, Y.
Anderson, G. D.
CA Eunice Kennedy Shriver Natl Inst
TI Can changes in angiogenic biomarkers between the first and second
trimesters of pregnancy predict development of pre-eclampsia in a
low-risk nulliparous patient population?
SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY
LA English
DT Article
DE Angiogenesis; endoglin; platelet growth factor; pre-eclampsia; sFlt-1
ID PLACENTA GROWTH-FACTOR; FOR-GESTATIONAL-AGE; SOLUBLE ENDOGLIN; MATERNAL
PLASMA; 1ST-TRIMESTER; WOMEN; 2ND-TRIMESTER; HYPERTENSION; MARKERS
AB Objective To determine if change in maternal angiogenic biomarkers between the first and second trimesters predicts pre-eclampsia in low-risk nulliparous women. Design A nested case-control study of change in maternal plasma soluble Flt-1 (sFlt-1), soluble endoglin (sEng) and placenta growth factor (PlGF). We studied 158 pregnancies complicated by preeclampsia and 468 normotensive nonproteinuric controls. Setting Amulticentre study in 16 academicmedical centres in the USA. Population Low-risk nulliparous women. Methods Luminex assays for PlGF, sFlt-1 and sEng performed on maternal EDTA plasma collected at 9-12, 15-18 and 23-26 weeks of gestation. Rate of change of analyte between first and either early or late second trimester was calculated with and without adjustment for baseline clinical characteristics. Main outcome measures Change in PlGF, sFlt-1 and sEng. Results Rates of change of PlGF, sEng and sFlt-1 between first and either early or late second trimesters were significantly different in women who developed pre-eclampsia, severe pre-eclampsia or early-onset pre-eclampsia compared with women who remained normotensive. Inclusion of clinical characteristics (race, body mass index and blood pressure at entry) increased sensitivity for detecting severe and particularly early-onset pre-eclampsia but not preeclampsia overall. Receiver operating characteristics curves for change from first to early second trimester in sEng, PlGF and sFlt-1 with clinical characteristics had areas under the curve of 0.88, 0.84 and 0.86, respectively, and for early-onset pre-eclampsia with sensitivities of 88% (95% CI 64-99), 77% (95% CI 50-93) and 77% (95% CI 50-93) for 80% specificity, respectively. Similar results were seen in the change from first to late second trimester. Conclusion Change in angiogenic biomarkers between first and early second trimester combined with clinical characteristics has strong utility for predicting early-onset pre-eclampsia.
C1 [Myatt, L.] Univ Cincinnati, Dept Obstet & Gynecol, Cincinnati, OH USA.
[Clifton, R. G.] George Washington Univ, Ctr Biostat, Washington, DC USA.
[Roberts, J. M.] Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA.
[Spong, C. Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Wapner, R. J.] Columbia Univ, Dept Obstet & Gynecol, New York, NY USA.
[Thorp, J. M., Jr.] Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA.
[Mercer, B. M.] Case Western Reserve Univ, MetroHlth Med Ctr, Dept Maternal Fetal Med, Cleveland, OH 44106 USA.
[Peaceman, A. M.] Northwestern Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA.
[Ramin, S. M.] Univ Texas Hlth Sci Ctr Houston, Dept Obstet Gynecol & Reprod Sci, Houston, TX 77030 USA.
[Carpenter, M. W.] Brown Univ, Dept Obstet & Gynecol, Providence, RI 02912 USA.
[Sciscione, A.] Christiana Care Hlth Syst, Dept Obstet & Gynecol, Newark, DE USA.
[Tolosa, J. E.] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA.
[Saade, G.] Univ Texas Med Branch, Dept Obstet & Gynecol, Galveston, TX 77555 USA.
[Sorokin, Y.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
[Anderson, G. D.] Univ Texas Med Branch, Dept Obstet & Gynecol, Galveston, TX 77555 USA.
RP Myatt, L (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Mail Code 7836,7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM myattl@uthscsa.edu
OI Peaceman, Alan/0000-0002-4515-4850
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) [HD34208, HD27869, HD40485, HD40560, HD40544,
HD34116, HD40512, HD21410, HD40545, HD40500, HD27915, HD34136, HD27860,
HD53118, HD53097, HD27917, HD36801]; National Heart, Lung, and Blood
Institute; National Center for Research Resources [M01 RR00080, UL1
RR024153, UL1 RR024989]
FX The project described was supported by grants from the Eunice Kennedy
Shriver National Institute of Child Health and Human Development (NICHD)
(HD34208, HD27869, HD40485, HD40560, HD40544, HD34116, HD40512, HD21410,
HD40545, HD40500, HD27915, HD34136, HD27860, HD53118, HD53097, HD27917,
and HD36801); the National Heart, Lung, and Blood Institute; and the
National Center for Research Resources (M01 RR00080, UL1 RR024153, UL1
RR024989) and its contents do not necessarily represent the official
view of NICHD, NHLBI, NCRR or NIH.
NR 21
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U1 0
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1470-0328
J9 BJOG-INT J OBSTET GY
JI BJOG
PD SEP
PY 2013
VL 120
IS 10
BP 1183
EP 1191
DI 10.1111/1471-0528.12128
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 199YT
UT WOS:000323032500004
PM 23331974
ER
PT J
AU Brasky, TM
Li, YL
Jaworowicz, DJ
Potischman, N
Ambrosone, CB
Hutson, AD
Nie, J
Shields, PG
Trevisan, M
Rudra, CB
Edge, SB
Freudenheim, JL
AF Brasky, Theodore M.
Li, Yanli
Jaworowicz, David J., Jr.
Potischman, Nancy
Ambrosone, Christine B.
Hutson, Alan D.
Nie, Jing
Shields, Peter G.
Trevisan, Maurizio
Rudra, Carole B.
Edge, Stephen B.
Freudenheim, Jo L.
TI Pregnancy-related characteristics and breast cancer risk
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Gestational hypertension; Gestational diabetes; Nausea; Pre-eclampsia;
Pregnancy weight gain; Vomiting
ID HUMAN CHORIONIC-GONADOTROPIN; CARCINOMA IN-SITU; HYPEREMESIS GRAVIDARUM;
POSTMENOPAUSAL WOMEN; SUBSEQUENT RISK; MATERNAL RISK; YOUNG-WOMEN; MCF-7
CELLS; EARLY-LIFE; NAUSEA
AB Breast tissues undergo extensive physiologic changes during pregnancy, which may affect breast carcinogenesis. Gestational hypertension, preeclampsia/eclampsia, gestational diabetes, pregnancy weight gain, and nausea and vomiting (N&V) during pregnancy may be indicative of altered hormonal and metabolic profiles and could impact breast cancer risk. Here, we examined associations between these characteristics of a woman's pregnancy and her subsequent breast cancer risk. Participants were parous women that were recruited to a population-based case-control study (Western New York Exposures and Breast Cancer Study). Cases (n = 960), aged 35-79 years, had incident, primary, histologically confirmed breast cancer. Controls (n = 1,852) were randomly selected from motor vehicle records (< 65 years) or Medicare rolls (a parts per thousand yen65 years). Women were queried on their lifetime pregnancy experiences. Multivariable-adjusted logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs). N&V during pregnancy was inversely associated with breast cancer risk. Relative to those who never experienced N&V, ever experiencing N&V was associated with decreased risk (OR 0.69, 95 % CI 0.56-0.84) as were increased N&V severity (p trend < 0.001), longer duration (p trend < 0.01), and larger proportion of affected pregnancies (p trend < 0.0001) among women with a parts per thousand yen3 pregnancies. Associations were stronger for more recent pregnancies (< 5 years). Findings did not differ by menopausal status or breast cancer subtype including estrogen receptor and HER2 expression status. Other pregnancy characteristics examined were not associated with risk. We observed strong inverse associations between pregnancy N&V and breast cancer risk. Replication of these findings and exploration of underlying mechanisms could provide important insight into breast cancer etiology and prevention.
C1 [Brasky, Theodore M.; Shields, Peter G.] Ohio State Univ, Coll Med, Div Canc Prevent & Control, Columbus, OH 43210 USA.
[Brasky, Theodore M.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43201 USA.
[Li, Yanli; Jaworowicz, David J., Jr.; Nie, Jing; Rudra, Carole B.; Freudenheim, Jo L.] SUNY Buffalo, Dept Social & Prevent Med, Sch Publ Hlth & Hlth Profess, Buffalo, NY 14260 USA.
[Jaworowicz, David J., Jr.] Cognigen Corp, Dept Pharmacometr Serv, Buffalo, NY USA.
[Potischman, Nancy] NCI, Off Associate Director, Appl Res Program, Bethesda, MD 20892 USA.
[Ambrosone, Christine B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[Hutson, Alan D.] SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Dept Biostat, Buffalo, NY 14260 USA.
[Trevisan, Maurizio] CUNY, Sch Biomed Educ, New York, NY 10021 USA.
[Edge, Stephen B.] Roswell Pk Canc Inst, Dept Surg Oncol, Buffalo, NY 14263 USA.
RP Brasky, TM (reprint author), Ohio State Univ, Ctr Comprehens Canc, 1590 N High St,Suite 525, Columbus, OH 43201 USA.
EM Theodore.Brasky@osumc.edu
FU National Institute on Alcohol Abuse and Alcoholism [P50-AA09802];
Department of Defense Breast Cancer Research Program [DAMD-179616202,
DAMD 17030446]
FX This work was supported in part by the National Institute on Alcohol
Abuse and Alcoholism (P50-AA09802), and the Department of Defense Breast
Cancer Research Program (DAMD-179616202, DAMD 17030446).
NR 53
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U1 0
U2 9
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD SEP
PY 2013
VL 24
IS 9
BP 1675
EP 1685
DI 10.1007/s10552-013-0242-9
PG 11
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 197VF
UT WOS:000322879200005
PM 23737027
ER
PT J
AU Cross, AJ
Hollenbeck, AR
Park, Y
AF Cross, Amanda J.
Hollenbeck, Albert R.
Park, Yikyung
TI A large prospective study of risk factors for adenocarcinomas and
malignant carcinoid tumors of the small intestine
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Demographic; Lifestyle; Risk factors; Small intestine; Cancer;
Adenocarcinoma; Carcinoid
ID SMALL-BOWEL CANCER; NEUROENDOCRINE TUMORS; COLORECTAL-CANCER;
UNITED-STATES; EPIDEMIOLOGY; SURVIVAL; ASSOCIATION; SMOKING; COHORT
AB Small intestinal cancer is increasing in the U.S.A, yet little is known about its etiology. Our aim was to prospectively evaluate risk factors for this malignancy by the two main histologic subtypes (adenocarcinomas and carcinoids).
Hazard ratios and 95 % confidence intervals (CI) were estimated for all incident small intestinal cancers (n = 237), adenocarcinomas (n = 84), and malignant carcinoids (n = 124), by demographic and lifestyle factors among 498,376 men and women.
Age was the only risk factor for adenocarcinomas (HR for a parts per thousand yen65 vs. 50-55 years = 3.12, 95 % CI 1.33, 7.31). Age (HR for a parts per thousand yen65 vs. 50-55 years = 3.31, 95 % CI 1.51, 7.28), male sex (HR = 1.44, 95 % CI 1.01, 2.05), body mass index (BMI, HR for a parts per thousand yen35 vs. 18.5-< 25 kg/m(2) = 1.95, 95 % CI 1.06, 3.58), and current menopausal hormone therapy use (HR = 1.94, 95 % CI 1.07, 3.50) were positively associated with malignant carcinoids. A family history of any cancer or colorectal cancer (HR = 1.42, 95 % CI 0.99, 2.03; 1.61, 0.97, 2.65, respectively), or a personal history of colorectal polyps (HR = 1.51, 95 % CI 0.92, 2.46) produced elevated, but not statistically significant, risks for malignant carcinoids. Race, education, diabetes, smoking, physical activity, and alcohol intake were not associated with either histologic subtype.
Risk factors differed according to cancer subtype; only age was associated with adenocarcinomas, whereas age, male sex, BMI, and menopausal hormone therapy use were positively associated with malignant carcinoids.
C1 [Cross, Amanda J.; Park, Yikyung] NCI, DCEG, DHHS, NIH, Rockville, MD 20852 USA.
[Hollenbeck, Albert R.] AARP, Washington, DC 20049 USA.
RP Cross, AJ (reprint author), NCI, DCEG, DHHS, NIH, 6120 Execut Blvd, Rockville, MD 20852 USA.
EM crossa@mail.nih.gov
OI Park, Yikyung/0000-0002-6281-489X
FU National Cancer Institute, National Institutes of Health, Department of
Health and Human Services
FX The authors would like to acknowledge Dr. Arthur Schatzkin who was the
principal investigator of the NIH-AARP Diet and Health study and
tragically passed away on January 20, 2011. Cancer incidence data from
the Atlanta metropolitan area were collected by the Georgia Center for
Cancer Statistics, Department of Epidemiology, Rollins School of Public
Health, Emory University, Atlanta, Georgia. Cancer incidence data from
California were collected by the California Cancer Registry, California
Department of Public Health's Cancer Surveillance and Research Branch,
Sacramento, California. Cancer incidence data from the Detroit
metropolitan area were collected by the Michigan Cancer Surveillance
Program, Community Health Administration, Lansing, Michigan. The Florida
cancer incidence data used in this report were collected by the Florida
Cancer Data System (Miami, Florida) under contract with the Florida
Department of Health, Tallahassee, Florida. The views expressed herein
are solely those of the authors and do not necessarily reflect those of
the FCDC or FDOH. Cancer incidence data from Louisiana were collected by
the Louisiana Tumor Registry, Louisiana State University Health Sciences
Center School of Public Health, New Orleans, Louisiana. Cancer incidence
data from New Jersey were collected by the New Jersey State Cancer
Registry, Cancer Epidemiology Services, New Jersey State Department of
Health, Trenton, New Jersey. Cancer incidence data from North Carolina
were collected by the North Carolina Central Cancer Registry, Raleigh,
North Carolina. Cancer incidence data from Pennsylvania were supplied by
the Division of Health Statistics and Research, Pennsylvania Department
of Health, Harrisburg, Pennsylvania. The Pennsylvania Department of
Health specifically disclaims responsibility for any analyses,
interpretations, or conclusions. Cancer incidence data from Arizona were
collected by the Arizona Cancer Registry, Division of Public Health
Services, Arizona Department of Health Services, Phoenix, Arizona.
Cancer incidence data from Texas were collected by the Texas Cancer
Registry, Cancer Epidemiology and Surveillance Branch, Texas Department
of State Health Services, Austin, Texas. Cancer incidence data from
Nevada were collected by the Nevada Central Cancer Registry, State
Health Division, State of Nevada Department of Health and Human
Services, Las Vegas, Nevada. We are indebted to the participants in the
NIH-AARP Diet and Health Study for their outstanding cooperation. We
also thank Sigurd Hermansen and Kerry Grace Morrissey from Westat for
study outcomes ascertainment and management, in addition to Leslie
Carroll and Adam Risch at Information Management Services for data
support and analysis. This work was supported by the Intramural Research
Program of the National Cancer Institute, National Institutes of Health,
Department of Health and Human Services.
NR 32
TC 3
Z9 3
U1 0
U2 9
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD SEP
PY 2013
VL 24
IS 9
BP 1737
EP 1746
DI 10.1007/s10552-013-0251-8
PG 10
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 197VF
UT WOS:000322879200011
PM 23812550
ER
PT J
AU Palmer, JR
Boggs, DA
Hatch, EE
Troisi, R
Titus-Ernstoff, L
Strohsnitter, WC
Adam, E
Hoover, RN
AF Palmer, Julie R.
Boggs, Deborah A.
Hatch, Elizabeth E.
Troisi, Rebecca
Titus-Ernstoff, Linda
Strohsnitter, William C.
Adam, Ervin
Hoover, Robert N.
TI Prenatal DES exposure in relation to breast size
SO CANCER CAUSES & CONTROL
LA English
DT Article
ID CANCER-RISK; MAMMARY-GLAND; UNITED-STATES; FOLLOW-UP;
DIETHYLSTILBESTROL; AUGMENTATION; MOTHERS; NUMBER
AB Prenatal DES exposure has been associated with increased risk of breast cancer, but the mechanisms are unknown. Larger bra cup size has also been associated with increased breast cancer risk, although not consistently. We investigated the relation of prenatal DES exposure to mammary gland mass, as estimated by bra cup size.
In 2006, 3,222 DES-exposed and 1,463 unexposed women reported their bra cup size, band size (chest circumference), and weight at age 20. Prevalence ratios (PR) were calculated for DES exposure in relation to large bra cup size, with control for year of birth and study cohort. Primary analyses were carried out among women who reported a chest circumference of no more than 32 inches because their cup size would be less influenced by fat mass.
Within this group, DES-exposed women had an estimated 45 % increased prevalence (95 % CI 0.97-2.18) of large cup size (C or greater) relative to unexposed women. The PR was further increased among women in this group who had a body mass index of < 21 at age 20: PR = 1.83 (95 % CI 1.11-3.00). The PR for high-dose DES exposure relative to no exposure was 1.67, 95 % CI 1.02-2.73, whereas there was no association of bra cup size with low-dose exposure.
These results provide support for the hypothesis that in utero DES exposure may result in greater mammary gland mass. Taken together with previous research on bra size and breast cancer risk, these findings suggest a mechanism for a possible association of in utero DES exposure with increased risk of breast cancer.
C1 [Palmer, Julie R.; Boggs, Deborah A.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA.
[Palmer, Julie R.; Hatch, Elizabeth E.] Boston Univ, Sch Med, Dept Epidemiol, Boston, MA 02118 USA.
[Troisi, Rebecca; Hoover, Robert N.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Titus-Ernstoff, Linda] Dartmouth Med Sch, Dept Community & Family Med, Lebanon, NH USA.
[Titus-Ernstoff, Linda] Dartmouth Med Sch, Dept Pediat, Lebanon, NH USA.
[Titus-Ernstoff, Linda] Norris Cotton Canc Ctr, Lebanon, NH USA.
[Strohsnitter, William C.] Tufts Univ New England Med Ctr, Dept Obstet & Gynecol, Boston, MA 02111 USA.
[Adam, Ervin] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA.
RP Palmer, JR (reprint author), Boston Univ, Slone Epidemiol Ctr, 1010 Commonwealth Ave, Boston, MA 02215 USA.
EM jpalmer@bu.edu
OI Hatch, Elizabeth/0000-0001-7901-3928; Palmer, Julie/0000-0002-6534-335X
FU National Cancer Institute, National Institutes of Health, U.S.
Department of Health and Human Services
FX This research was support by a contract from the National Cancer
Institute, National Institutes of Health, U.S. Department of Health and
Human Services. We thank the field center study managers, Diane
Anderson, Elizabeth Barnard, Toni Oliver, Elaine Campbell, Polly
Goralski, Kathleen Rowlings, Helen Bond, Ann Urbanovitch, and Kathyln
Tucke. We also appreciate the support of Cathy Ann Grundmayer, Shelley
Niwa, and Bob Saal of Westat, Inc., for study- wide coordination
efforts. Finally, we thank the DES-exposed and unexposed daughters for
their longstanding participation in this study.
NR 30
TC 3
Z9 3
U1 1
U2 11
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD SEP
PY 2013
VL 24
IS 9
BP 1757
EP 1761
DI 10.1007/s10552-013-0248-3
PG 5
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 197VF
UT WOS:000322879200013
PM 23775027
ER
PT J
AU Adiseshaiah, PP
Clogston, JD
McLeland, CB
Rodriguez, J
Potter, TM
Neun, BW
Skoczen, SL
Shanmugavelandy, SS
Kester, M
Stern, ST
McNeil, SE
AF Adiseshaiah, Pavan P.
Clogston, Jeffrey D.
McLeland, Christopher B.
Rodriguez, Jamie
Potter, Timothy M.
Neun, Barry W.
Skoczen, Sarah L.
Shanmugavelandy, Sriram S.
Kester, Mark
Stern, Stephan T.
McNeil, Scott E.
TI Synergistic combination therapy with nanoliposomal C6-ceramide and
vinblastine is associated with autophagy dysfunction in hepatocarcinoma
and colorectal cancer models
SO CANCER LETTERS
LA English
DT Article
DE Combination therapy; Autophagy; Ceramide
ID MALIGNANT GLIOMA-CELLS; PORCINE KIDNEY-CELLS; INDUCED APOPTOSIS;
TUMOR-SUPPRESSOR; HEPATOCELLULAR-CARCINOMA; TARGETING AUTOPHAGY;
CERAMIDE; TUMORIGENESIS; CYTOTOXICITY; INHIBITION
AB Autophagy, a catabolic survival pathway, is gaining attention as a potential target in cancer. In human liver and colon cancer cells, treatment with an autophagy inducer, nanoliposomal C6-ceramide, in combination with the autophagy maturation inhibitor, vinblastine, synergistically enhanced apoptotic cell death. Combination treatment resulted in a marked increase in autophagic vacuole accumulation and decreased autophagy maturation, without diminution of the autophagy flux protein P62. In a colon cancer xenograft model, a single intravenous injection of the drug combination significantly decreased tumor growth in comparison to the individual treatments. Most importantly, the combination treatment did not result in increased toxicity as assessed by body weight loss. The mechanism of combination treatment-induced cell death both in vitro and in vivo appeared to be apoptosis. Supportive of autophagy flux blockade as the underlying synergy mechanism, treatment with other autophagy maturation inhibitors, but not autophagy initiation inhibitors, were similarly synergistic with C6-ceramide. Additionally, knockout of the autophagy protein Beclin-1 suppressed combination treatment-induced apoptosis in vitro. In conclusion, in vitro and in vivo data support a synergistic antitumor activity of the nanoliposomal C6-ceramide and vinblastine combination, potentially mediated by an autophagy mechanism. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
C1 [Adiseshaiah, Pavan P.; Clogston, Jeffrey D.; McLeland, Christopher B.; Rodriguez, Jamie; Potter, Timothy M.; Neun, Barry W.; Skoczen, Sarah L.; Stern, Stephan T.; McNeil, Scott E.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Nanotechnol Characterizat Lab, Adv Technol Program, Frederick, MD 21702 USA.
[Shanmugavelandy, Sriram S.; Kester, Mark] Penn State Univ, Dept Pharmacol, Coll Med, Hershey, PA 17033 USA.
RP Stern, ST (reprint author), SAIC Frederick Inc, Frederick Natl Lab Canc Res, Nanotechnol Characterizat Lab, Adv Technol Program, Frederick, MD 21702 USA.
EM sternstephan@mail.nih.gov
RI Nanotechnology Characterization Lab, NCL/K-8454-2012
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; Ebberly Fund of Penn State College of Medicine
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
contract HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government. The
project was also funded, in part (MK), through support from the Ebberly
Fund of Penn State College of Medicine.
NR 50
TC 22
Z9 23
U1 0
U2 32
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3835
EI 1872-7980
J9 CANCER LETT
JI Cancer Lett.
PD SEP 1
PY 2013
VL 337
IS 2
BP 254
EP 265
DI 10.1016/j.canlet.2013.04.034
PG 12
WC Oncology
SC Oncology
GA 201JP
UT WOS:000323138200013
PM 23664889
ER
PT J
AU Camargo, JF
Lobo, SA
Hsu, AP
Zerbe, CS
Wormser, GP
Holland, SM
AF Camargo, Jose F.
Lobo, Stephen A.
Hsu, Amy P.
Zerbe, Christa S.
Wormser, Gary P.
Holland, Steven M.
TI MonoMAC Syndrome in a Patient With a GATA2 Mutation: Case Report and
Review of the Literature
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Review
DE GATA2; MonoMAC; monocytopenia; mycobacterial infection; immunodeficiency
ID SPORADIC MONOCYTOPENIA; AUTOSOMAL-DOMINANT; IMMUNODEFICIENCY;
MYELODYSPLASIA; LYMPHEDEMA; DISEASE
AB We report a case of MonoMAC syndrome in a patient with a GATA2 mutation and discuss the manifestations, diagnosis, and treatment of this novel immunodeficiency disorder.
C1 [Camargo, Jose F.; Lobo, Stephen A.; Wormser, Gary P.] New York Med Coll, Dept Med, Div Infect Dis, Valhalla, NY 10595 USA.
[Hsu, Amy P.; Zerbe, Christa S.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
RP Camargo, JF (reprint author), New York Med Coll, Div Infect Dis, Munger Pavil,Rm 245, Valhalla, NY 10595 USA.
EM josefcamargo@gmail.com
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This work was supported in part by the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 12
TC 20
Z9 20
U1 0
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD SEP 1
PY 2013
VL 57
IS 5
BP 697
EP 699
DI 10.1093/cid/cit368
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 199DJ
UT WOS:000322974400010
PM 23728141
ER
PT J
AU Kahn, JA
Xu, JH
Kapogiannis, BG
Rudy, B
Gonin, R
Liu, N
Wilson, CM
Worrell, C
Squires, KE
AF Kahn, Jessica A.
Xu, Jiahong
Kapogiannis, Bill G.
Rudy, Bret
Gonin, Rene
Liu, Nancy
Wilson, Craig M.
Worrell, Carol
Squires, Kathleen E.
TI Immunogenicity and Safety of the Human Papillomavirus 6, 11, 16, 18
Vaccine in HIV-Infected Young Women
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE immunogenicity; safety; human papillomavirus; vaccine; HIV infected
ID CERVICAL INTRAEPITHELIAL NEOPLASIA; IMMUNODEFICIENCY-VIRUS TYPE-1;
PARTICLE VACCINE; QUADRIVALENT VACCINE; DOUBLE-BLIND; EFFICACY; RISK;
LESIONS; TRIAL; HPV
AB Background. The objective of this study was to determine whether the 3-dose quadrivalent human papillomavirus (HPV) vaccine series (HPV-6, -11, -16, -18) is immunogenic and safe in young women infected with human immunodeficiency virus (HIV).
Methods. We enrolled 99 women aged 16-23 years in a phase 2, open-label, multicenter trial, conducted from 2008 to 2011 by the Adolescent Medicine Trials Network for HIV/AIDS Interventions. Outcome measures were immunogenicity 4 weeks after dose 3, measured by (1) geometric mean titers (GMTs) and (2) seroconversion rates for HPV-6, -11, -16, and -18, among those seronegative and HPV DNA negative for each type. Immune responses were compared to those of a historical comparison group of HIV-negative women (n = 267) using univariate methods. Clinical and laboratory adverse events were assessed after each dose.
Results. The mean age of subjects was 21.4 years; 80% were non-Hispanic black, 69 were not taking antiretroviral therapy (ART), and 30 were taking ART. No differences in GMTs were noted among participants taking ART vs the comparison group, but GMTs were lower in participants not taking ART vs the comparison group for HPV-16 (2393 vs 3892 milli-Merck units per milliliter [mMU/mL], P = .012) and HPV-18 (463 vs 801 mMU/mL, P = .003). Seroconversion rates were 100% for HPV-6, -11, -16, and -18 among participants taking ART. Rates ranged from 92.3% (for HPV-18) to 100.0% (for HPV-6) among participants not taking ART. One severe adverse event (fatigue) was noted.
Conclusions. In a sample of HIV-infected women who were HPV DNA and HPV seronegative, immune responses to HPV vaccination were generally robust and the vaccine was well tolerated.
C1 [Kahn, Jessica A.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Kahn, Jessica A.] Univ Cincinnati, Coll Med, Cincinnati, OH 45221 USA.
[Xu, Jiahong; Gonin, Rene; Liu, Nancy] Westat Corp, Rockville, MD USA.
[Kapogiannis, Bill G.; Worrell, Carol] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, NIH, Rockville, MD USA.
[Rudy, Bret] NYU, Sch Med, New York, NY USA.
[Wilson, Craig M.] Univ Alabama Birmingham, Sch Publ Hlth, Birmingham, AL USA.
[Squires, Kathleen E.] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA.
RP Kahn, JA (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Adolescent Med, MLC 4000,3333 Burnet Ave, Cincinnati, OH 45229 USA.
EM jessica.kahn@cchmc.org
FU AIDS Interventions (ATN) from the National Institutes of Health through
the NICHD [U01 HD 040533, U01 HD 040474]; National Institute on Drug
Abuse; National Institute of Mental Health; National Institutes of
Health [AI-51519]; Einstein Cancer Research Center from the National
Cancer Institute [P30CA013330]; General Clinical Research Center Program
of the National Center for Research Resources, National Institutes of
Health, Department of Health and Human Services [M01RR020359];
University of Pennsylvania/Children's Hospital of Philadelphia
[NCRRUL1-RR-024134]; Louisiana Board of Regents RC/EEP [RC/EEP06]; Merck
Co, Inc.
FX This work was supported by AIDS Interventions (ATN) from the National
Institutes of Health (grant numbers U01 HD 040533 and U01 HD 040474)
through the NICHD (to B. G. K., C. W.), with supplemental funding from
the National Institute on Drug Abuse (N. Borek) and the National
Institute of Mental Health (P. Brouwers, S. Allison). The study was
scientifically reviewed by the ATN's Therapeutic Leadership Group.
ATN-affiliated investigators and program staff supervised the design and
conduct of the study; collection, management, analysis, and
interpretation of the data; and preparation, review, and approval of the
manuscript. Network, scientific, and logistical support was provided by
the ATN Coordinating Center (C. Wilson, C. Partlow) at The University of
Alabama at Birmingham. Network operations and analytic support was
provided by the ATN Data and Operations Center at Westat, Inc (J.
Korelitz, B. Driver). The following ATN sites participated in this
study: Children's National Medical Center (D'Angelo, Hagler, Trexler);
Children's Hospital of Philadelphia (Douglas, Tanney, DiBenedetto); John
H. Stroger Jr Hospital of Cook County and the Ruth M. Rothstein CORE
Center (Martinez, Bojan, Jackson, Henry-Reid); University of Puerto Rico
(Febo, Ayala-Flores, Fuentes-Gomez); Montefiore Medical Center
(Futterman, Enriquez-Bruce, Campos); Tulane University Health Sciences
Center (Abdalian, Kozina, Baker); University of Miami School of Medicine
(Friedman, Maturo, Major-Wilson); Children's Diagnostic and Treatment
Center (Puga, Leonard, Inman); St Jude's Children's Research Hospital
(Flynn, Dillard); Children's Memorial (Garofalo, Brennan, Flanagan);
University of South Florida, Tampa (Emmanuel, Straub, Lujan-Zilberman,
Julian, Rebolledo); Children's Hospital of Los Angeles (Belzer, Flores,
Tucker); Mount Sinai Medical Center (Steever, Geiger); and University of
Maryland (Peralta, Gorle).; In addition, R. Burk utilized core
facilities of the Einstein-Montefiore Center for AIDS funded by the
National Institutes of Health (AI-51519) and the Einstein Cancer
Research Center (grant number P30CA013330) from the National Cancer
Institute. Two of the sites utilized their General Clinical Research
Center/Pediatric Clinical Research Center for the study. The centers
were supported by grants from the General Clinical Research Center
Program of the National Center for Research Resources, National
Institutes of Health, Department of Health and Human Services as
follows: Children's National Medical Center (grant number M01RR020359)
and University of Pennsylvania/Children's Hospital of Philadelphia
(grant number NCRRUL1-RR-024134). The site at Tulane University Health
Sciences Center utilized its Clinical and Translational Research Center
for the study; the center was supported in whole or in part by funds
provided through the Louisiana Board of Regents RC/EEP (grant number
RC/EEP06). Vaccine and HPV GMTs were provided through the
Investigator-Initiated Studies Program of Merck & Co, Inc.
NR 33
TC 31
Z9 31
U1 0
U2 11
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 SEP 1
PY 2013
VL 57
IS 5
BP 735
EP 744
DI 10.1093/cid/cit319
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 199DJ
UT WOS:000322974400017
PM 23667266
ER
PT J
AU Falcone, EL
Adegbulugbe, AA
Sheikh, V
Imamichi, H
Dewar, RL
Hammoud, DA
Sereti, I
Lane, HC
AF Falcone, E. Liana
Adegbulugbe, Ademiposi A.
Sheikh, Virginia
Imamichi, Hiromi
Dewar, Robin L.
Hammoud, Dima A.
Sereti, Irini
Lane, H. Clifford
TI Cerebrospinal Fluid HIV-1 Compartmentalization in a Patient With AIDS
and Acute Varicella-Zoster Virus Meningomyeloradiculitis
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Editorial Material
DE human immunodeficiency virus; viral quasispecies; central nervous system
compartmentalization; varicella-zoster virus; meningomyeloradiculitis
ID CENTRAL-NERVOUS-SYSTEM; ANTIRETROVIRAL THERAPY; MYELITIS; TYPE-1; BLOOD;
INFECTION; BRAIN; COMPLICATIONS; RESERVOIRS; SEQUENCES
AB We report a case of AIDS presenting as varicella-zoster virus (VZV) meningomyeloradiculitis associated with human immunodeficiency virus (HIV) quasispecies compartmentalization within the cerebrospinal fluid (CSF), and a CSF viral load that was 1 log higher than in peripheral blood. Prolonged antiviral therapy for both VZV and HIV type 1 was associated with partial resolution.
C1 [Falcone, E. Liana] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Sheikh, Virginia; Imamichi, Hiromi; Sereti, Irini; Lane, H. Clifford] NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Adegbulugbe, Ademiposi A.] Washington Hosp Ctr, Dept Med, Infect Dis Sect, Washington, DC 20010 USA.
[Dewar, Robin L.] NCI Frederick, Clin Serv Program, SAIC Frederick, Bethesda, MD USA.
[Hammoud, Dima A.] NIH, Ctr Infect Dis Imaging Radiol & Imaging Sci, Bethesda, MD 20892 USA.
RP Falcone, EL (reprint author), NIAID, Lab Clin Infect Dis, NIH, CRC, 10 Ctr Dr,Rm B3-4141,MSC 1684, Bethesda, MD 20892 USA.
EM emilia.falcone@nih.gov
RI Hammoud, Dima/C-2286-2015
NR 28
TC 10
Z9 10
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD SEP 1
PY 2013
VL 57
IS 5
BP E135
EP E142
DI 10.1093/cid/cit356
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 199DJ
UT WOS:000322974400001
PM 23728149
ER
PT J
AU Larochelle, A
AF Larochelle, Andre
TI Generation of red blood cells in vitro: monitoring the process for
improved efficiency
SO CYTOTHERAPY
LA English
DT Editorial Material
ID STEM-CELLS; HEMATOPOIETIC STEM; PROGENITOR CELLS; DIFFERENTIATION;
ERYTHROBLASTS; ENUCLEATION; TRANSFUSION; EXPANSION
C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Larochelle, A (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10CRC,Room 5E-5130,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM larochea@nhlbi.nih.gov
FU Intramural NIH HHS [Z99 HL999999, ZIA HL006172-01]
NR 15
TC 2
Z9 2
U1 0
U2 5
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1465-3249
J9 CYTOTHERAPY
JI Cytotherapy
PD SEP
PY 2013
VL 15
IS 9
BP 1043
EP 1045
DI 10.1016/j.jcyt.2013.06.015
PG 3
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology; Hematology; Medicine, Research & Experimental
SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research
& Experimental Medicine
GA 201KU
UT WOS:000323141300001
PM 23911006
ER
PT J
AU Zeng, XK
Lin, XH
Hou, SX
AF Zeng, Xiankun
Lin, Xinhua
Hou, Steven X.
TI The Osa-containing SWI/SNF chromatin-remodeling complex regulates stem
cell commitment in the adult Drosophila intestine
SO DEVELOPMENT
LA English
DT Article
DE Chromatin-remodeling factor; SWI/SNF; Osa; Intestinal stem cells;
Self-renewal; Differentiation; Drosophila
ID TARGET GENES; MIDGUT; PROTEIN; DIFFERENTIATION; TRANSCRIPTION;
PLURIPOTENCY; HOMEOSTASIS; ACTIVATION; SUPPRESSOR; HOMOLOGY
AB The proportion of stem cells versus differentiated progeny is well balanced to maintain tissue homeostasis, which in turn depends on the balance of the different signaling pathways involved in stem cell self-renewal versus lineage-specific differentiation. In a screen for genes that regulate cell lineage determination in the posterior midgut, we identified that the Osa-containing SWI/SNF (Brahma) chromatin-remodeling complex regulates Drosophila midgut homeostasis. Mutations in subunits of the Osa-containing complex result in intestinal stem cell (ISC) expansion as well as enteroendocrine (EE) cell reduction. We further demonstrated that Osa regulates ISC self-renewal and differentiation into enterocytes by elaborating Notch signaling, and ISC commitment to differentiation into EE cells by regulating the expression of Asense, an EE cell fate determinant. Our data uncover a unique mechanism whereby the commitment of stem cells to discrete lineages is coordinately regulated by chromatin-remodeling factors.
C1 [Zeng, Xiankun; Hou, Steven X.] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA.
[Lin, Xinhua] Chinese Acad Sci, Inst Zool, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100101, Peoples R China.
[Lin, Xinhua] Cincinnati Childrens Hosp Med Ctr, Div Dev Biol, Cincinnati, OH 45229 USA.
RP Zeng, XK (reprint author), NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA.
EM zengx2@mail.nih.gov; hous@mail.nih.gov
FU Intramural Research Program of the National Cancer Institute, National
Institutes of Health; Strategic Priority Research Program of the Chinese
Academy of Sciences Grant [XDA01010101]; Nature Sciences Foundation of
China [31030049]
FX This research was supported by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health. Work in the
X.L. laboratory was supported by grants from the Strategic Priority
Research Program of the Chinese Academy of Sciences Grant [XDA01010101]
and the Nature Sciences Foundation of China [31030049] to X.L. Deposited
in PMC for release after 12 months.
NR 42
TC 20
Z9 20
U1 1
U2 8
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 SEP 1
PY 2013
VL 140
IS 17
BP 3532
EP 3540
DI 10.1242/dev.096891
PG 9
WC Developmental Biology
SC Developmental Biology
GA 200BN
UT WOS:000323041400005
PM 23942514
ER
PT J
AU Kaneko, KJ
DePamphilis, ML
AF Kaneko, Kotaro J.
DePamphilis, Melvin L.
TI TEAD4 establishes the energy homeostasis essential for blastocoel
formation
SO DEVELOPMENT
LA English
DT Article
DE Tead4; Blastocyst; Trophectoderm; Blastocoel; Oxidative stress;
Anti-oxidant; Mouse
ID PREIMPLANTATION MOUSE EMBRYOS; INNER CELL MASS; GENE-EXPRESSION;
MAMMALIAN DEVELOPMENT; TRANSCRIPTION FACTORS; OXIDATIVE STRESS;
AMINO-ACIDS; IN-VITRO; TROPHOBLAST DEVELOPMENT; TROPHECTODERM LINEAGE
AB It has been suggested that during mouse preimplantation development, the zygotically expressed transcription factor TEAD4 is essential for specification of the trophectoderm lineage required for producing a blastocyst. Here we show that blastocysts can form without TEAD4 but that TEAD4 is required to prevent oxidative stress when blastocoel formation is accompanied by increased oxidative phosphorylation that leads to the production of reactive oxygen species (ROS). Both two-cell and eight-cell Tead4(-/-) embryos developed into blastocysts when cultured under conditions that alleviate oxidative stress, and Tead4(-/-) blastocysts that formed under these conditions expressed trophectoderm-associated genes. Therefore, TEAD4 is not required for specification of the trophectoderm lineage. Once the trophectoderm was specified, Tead4 was not essential for either proliferation or differentiation of trophoblast cells in culture. However, ablation of Tead4 in trophoblast cells resulted in reduced mitochondrial membrane potential. Moreover, Tead4 suppressed ROS in embryos and embryonic fibroblasts. Finally, ectopically expressed TEAD4 protein could localize to the mitochondria as well as to the nucleus, a property not shared by other members of the TEAD family. These results reveal that TEAD4 plays a crucial role in maintaining energy homeostasis during preimplantation development.
C1 [Kaneko, Kotaro J.; DePamphilis, Melvin L.] NICHHD, NIH, Bethesda, MD 20892 USA.
RP Kaneko, KJ (reprint author), NICHHD, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM KanekoK@mail.nih.gov
FU Eunice Shriver Kennedy National Institute of Child Health and Human
Development (NICHD) intramural research program
FX This work was supported financially by the Eunice Shriver Kennedy
National Institute of Child Health and Human Development (NICHD)
intramural research program. Deposited in PMC for release after 12
months.
NR 90
TC 19
Z9 19
U1 0
U2 8
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 SEP 1
PY 2013
VL 140
IS 17
BP 3680
EP 3690
DI 10.1242/dev.093799
PG 11
WC Developmental Biology
SC Developmental Biology
GA 200BN
UT WOS:000323041400019
PM 23903192
ER
PT J
AU Meerson, A
Traurig, M
Ossowski, V
Fleming, JM
Mullins, M
Baier, LJ
AF Meerson, A.
Traurig, M.
Ossowski, V.
Fleming, J. M.
Mullins, M.
Baier, L. J.
TI Human adipose microRNA-221 is upregulated in obesity and affects fat
metabolism downstream of leptin and TNF-alpha
SO DIABETOLOGIA
LA English
DT Article
DE ADIPOR1; ETS1; Insulin resistance; Leptin; MicroRNA; miR-221; Obesity;
Pima; Tumour necrosis factor
ID INSULIN-RESISTANCE; PPAR-GAMMA; ADIPOCYTE DIFFERENTIATION; SUBCUTANEOUS
ADIPOSE; RECEPTOR-ALPHA; EXPRESSION; ETS; MIR-221; CANCER; TISSUE
AB MicroRNAs (miRNAs) are short endogenous RNAs that regulate multiple biological processes including adipogenesis and fat metabolism. We sought to identify miRNAs that correlate with BMI and to elucidate their upstream regulation and downstream targets.
Microarray-based expression profiling of 233 miRNAs was performed on subcutaneous abdominal adipose tissue biopsies from 29 non-diabetic Pima Indian participants. Correlation of the expression levels of eight miRNAs with BMI was assessed by quantitative reverse transcription (QRT) PCR in adipose samples from 80 non-diabetic Pima Indians with a BMI of 21.6-54.0 kg/m(2). The upstream regulation of one of these miRNAs, miR-221, was tested by treating cultured human pre-adipocytes with leptin, TNF-alpha and insulin. Predicted targets of miR-221 were validated using QRT-PCR, immunoblots and luciferase assays. The downstream effects of miR-221 overexpression were assayed by proteomic analysis.
Expression levels of miR-221 were positively correlated with BMI (particularly in women) and fasting insulin concentrations, while the levels of miR-193a-3p and miR-193b-5p were negatively correlated with BMI; other miRNAs did not show significant associations in the 80 samples. miR-221 was downregulated by leptin and TNF-alpha treatment in cultured human pre-adipocytes. Conversely, miR-221 overexpression upregulated several proteins involved in fat metabolism, mimicking peroxisome proliferator-activated receptor (PPAR) activation. Furthermore, miR-221 directly downregulated the adiponectin receptor 1 (ADIPOR1) and the transcription factor v-ets erythroblastosis virus E26 oncogene homolog 1 (ETS1). Adiponectin signalling is known to promote insulin sensitivity, and ETS1 is crucial for angiogenesis.
Our data suggest that miR-221 may contribute to the development of the insulin resistance that typically accompanies obesity, by affecting PPAR signalling pathways and by directly downregulating ADIPOR1 and ETS1.
C1 [Meerson, A.; Traurig, M.; Ossowski, V.; Fleming, J. M.; Mullins, M.; Baier, L. J.] NIDDK, NIH, Phoenix, AZ 85004 USA.
RP Baier, LJ (reprint author), NIDDK, NIH, 445 North 5th St, Phoenix, AZ 85004 USA.
EM lbaier@phx.niddk.nih.gov
FU NIDDK
FX This research was funded by the intramural programme of NIDDK.
NR 51
TC 40
Z9 49
U1 3
U2 32
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
J9 DIABETOLOGIA
JI Diabetologia
PD SEP
PY 2013
VL 56
IS 9
BP 1971
EP 1979
DI 10.1007/s00125-013-2950-9
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 200HV
UT WOS:000323059800016
PM 23756832
ER
PT J
AU Franks, PW
Christophi, CA
Jablonski, KA
Delahanty, LM
Horton, ES
Knowler, WC
Florez, JC
AF Franks, P. W.
Christophi, C. A.
Jablonski, K. A.
Delahanty, L. M.
Horton, E. S.
Knowler, W. C.
Florez, J. C.
CA Diabet Prevention Program Res Grp
TI RETRACTED ARTICLE: Common variation in PPARGC1A/B and progression to
diabetes or change in metabolic traits following preventive
interventions: the Diabetes Prevention Program (vol 59, pg 2672, 2010)
SO DIABETOLOGIA
LA English
DT Correction
C1 [Franks, P. W.] Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden.
[Franks, P. W.] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
[Franks, P. W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Franks, P. W.; Christophi, C. A.; Jablonski, K. A.] Washington Univ, Diabet Prevent Program Coordinating Ctr, Ctr Biostat, Rockville, MD 20852 USA.
[Delahanty, L. M.; Florez, J. C.] Massachusetts Gen Hosp, Dept Med, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA.
[Horton, E. S.; Florez, J. C.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA.
[Knowler, W. C.] Natl Inst Diabet & Digest & Kidney Dis, Diabet Epidemiol & Clin Res Sect, NIH, Phoenix, AZ USA.
[Florez, J. C.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
RP Franks, PW (reprint author), Washington Univ, Diabet Prevent Program Coordinating Ctr, Ctr Biostat, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA.
EM paul.franks@med.lu.se
NR 1
TC 1
Z9 1
U1 6
U2 16
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
J9 DIABETOLOGIA
JI Diabetologia
PD SEP
PY 2013
VL 56
IS 9
BP 2102
EP 2102
DI 10.1007/s00125-013-2911-3
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 200HV
UT WOS:000323059800033
ER
PT J
AU Islami, F
Cao, Y
Kamangar, F
Nasrollahzadeh, D
Marjani, HA
Shakeri, R
Fahimi, S
Sotoudeh, M
Dawsey, SM
Abnet, CC
Boffetta, P
Malekzadeh, R
AF Islami, Farhad
Cao, Yin
Kamangar, Farin
Nasrollahzadeh, Dariush
Marjani, Haji-Amin
Shakeri, Ramin
Fahimi, Saman
Sotoudeh, Masoud
Dawsey, Sanford M.
Abnet, Christian C.
Boffetta, Paolo
Malekzadeh, Reza
TI Reproductive factors and risk of esophageal squamous cell carcinoma in
northern Iran: a case-control study in a high-risk area and literature
review
SO EUROPEAN JOURNAL OF CANCER PREVENTION
LA English
DT Article
DE case-control study; esophageal cancer; miscarriage; parity;
reproductive; squamous cell carcinoma
ID GASTRIC-CANCER; POSTMENOPAUSAL WOMEN; HORMONAL FACTORS; 1ST PREGNANCY;
SEX-HORMONES; COHORT; METAANALYSIS; ESTROGEN; ALCOHOL; TOBACCO
AB Several epidemiologic studies have suggested an inverse association between female reproductive factors and the risk of esophageal squamous cell carcinoma (ESCC), but the evidence is not conclusive. We examined the association of the number of pregnancies, live births, and miscarriages/stillbirths in women and the association of the number of children in both sexes with the risk of ESCC in Golestan Province, a high-risk area in Iran. Data from 297 histopathologically confirmed ESCC cases (149 women) and 568 controls (290 women) individually matched to cases for age, sex, and neighborhood of residence were included in this analysis. Conditional logistic regression was used to calculate odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). The average numbers of live births and miscarriages/stillbirths among the controls were 8.2 and 0.8, respectively. Women with six or more live births were at approximate to 1/3 the risk of ESCC as those with 0-3 live births; the OR (95% CI) for having 6-7 live births was 0.33 (0.12-0.92). In contrast, the number of miscarriages/stillbirths was associated with an increase in the risk of ESCC. The OR (95% CI) for at least three versus no miscarriages/stillbirths was 4.43 (2.11-9.33). The number of children in women was suggestive of an inverse association with ESCC, but this association was not statistically significant; in men, no association was observed. The findings of this study support a protective influence of female hormonal factors on the risk of ESCC. However, further epidemiological and mechanistic studies are required to prove a protective association. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Islami, Farhad; Nasrollahzadeh, Dariush; Marjani, Haji-Amin; Shakeri, Ramin; Sotoudeh, Masoud; Malekzadeh, Reza] Univ Tehran Med Sci, Shariati Hosp, Digest Dis Res Ctr, Tehran, Iran.
[Islami, Farhad; Cao, Yin; Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY 10029 USA.
[Islami, Farhad; Cao, Yin; Boffetta, Paolo] Mt Sinai Sch Med, Inst Transit Epidemiol, New York, NY 10029 USA.
[Cao, Yin] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Kamangar, Farin] Morgan State Univ, Sch Community Hlth & Policy, Dept Publ Hlth Anal, Baltimore, MD 21239 USA.
[Dawsey, Sanford M.; Abnet, Christian C.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Nasrollahzadeh, Dariush] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Fahimi, Saman] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
[Boffetta, Paolo] Int Prevent Res Inst, Lyon, France.
[Marjani, Haji-Amin] Golestan Univ Med Sci, Res Ctr Gastroenterol & Hepatol, Gorgan, Iran.
RP Islami, F (reprint author), Mt Sinai Sch Med, Tisch Canc Inst, 1 Gustave L Levy Pl,POB 1057, New York, NY 10029 USA.
EM farhad.islami@mssm.edu
RI Abnet, Christian/C-4111-2015;
OI Abnet, Christian/0000-0002-3008-7843; , Ramin/0000-0003-0487-3629;
Malekzadeh, Reza/0000-0003-1043-3814
FU Digestive Disease Research Center of Tehran University of Medical
Sciences [82-603]; Division of Cancer Epidemiology and Genetics,
National Cancer Institute, National Institutes of Health
FX The Golestan Case-Control Study was supported by the Digestive Disease
Research Center of Tehran University of Medical Sciences (grant number
82-603) and intramural funds of the Division of Cancer Epidemiology and
Genetics, National Cancer Institute, National Institutes of Health. The
funding sources had no role in the design, conduct, statistical analysis
and interpretation of results, or writing of the manuscript.
NR 37
TC 8
Z9 9
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0959-8278
J9 EUR J CANCER PREV
JI Eur. J. Cancer Prev.
PD SEP
PY 2013
VL 22
IS 5
BP 461
EP 466
DI 10.1097/CEJ.0b013e32835c7f87
PG 6
WC Oncology
SC Oncology
GA 202OD
UT WOS:000323226200013
PM 23238586
ER
PT J
AU Yan, T
Li, QZ
Li, YZ
Li, ZH
Zheng, G
AF Yan, Ting
Li, Qizhai
Li, Yuanzhang
Li, Zhaohai
Zheng, Gang
TI Genetic Association With Multiple Traits in the Presence of Population
Stratification
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE inverted regression; genomic control; MultiPhen; pleiotropy;
proportional odds model; population structure; principal component
analysis; variance inflation factor
ID GENOME-WIDE ASSOCIATION; PRINCIPAL-COMPONENTS; QUANTITATIVE TRAITS; RARE
VARIANTS; SUBSTRUCTURE; BINARY; TESTS; POWER; MODEL
AB Testing association between a genetic marker and multiple-dependent traits is a challenging task when both binary and quantitative traits are involved. The inverted regression model is a convenient method, in which the traits are treated as predictors although the genetic marker is an ordinal response. It is known that population stratification (PS) often affects population-based association studies. However, how it would affect the inverted regression for pleiotropic association, especially with the mixed types of traits (binary and quantitative), is not examined and the performance of existing methods to correct for PS using the inverted regression analysis is unknown. In this paper, we focus on the methods based on genomic control and principal component analysis, and investigate type I error of pleiotropic association using the inverted regression model in the presence of PS with allele frequencies and the distributions (or disease prevalences) of multiple traits varying across the subpopulations. We focus on common alleles but simulation results for a rare variant are also reported. An application to the HapMap data is used for illustration.
C1 [Yan, Ting] Cent China Normal Univ, Wuhan, Peoples R China.
[Yan, Ting; Li, Zhaohai] George Washington Univ, Washington, DC USA.
[Yan, Ting] Digital Syst Inc, Chevy Chase, MD USA.
[Li, Qizhai] Chinese Acad Sci, Beijing, Peoples R China.
[Li, Yuanzhang] Walter Reed Army Inst Res, Silver Spring, MD USA.
[Zheng, Gang] NHLBI, Bethesda, MD 20892 USA.
RP Zheng, G (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr, Bethesda, MD 20892 USA.
EM zhengg@nhlbi.nih.gov
OI Li, Yuanzhang/0000-0001-8872-4430
FU Department of the Army In-House Laboratory Independent Research
[W81XWH-11-C-0082]; Small Business Innovation Research [W81XWH11C0511]
FX The part of effort (authors from GWU and WRAIR) is funded by Department
of the Army In-House Laboratory Independent Research W81XWH-11-C-0082
and the Small Business Innovation Research W81XWH11C0511. The views
expressed are those of the authors and should not be construed to
represent the positions of the Department of the Army, Department of
Defense, or National Institutes of Health. None of the authors have any
associations, financial or otherwise, that may present a conflict of
interest. The authors thank Paul O'Reilly for the thoughtful comments
and suggestions.
NR 29
TC 7
Z9 7
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD SEP
PY 2013
VL 37
IS 6
BP 571
EP 580
DI 10.1002/gepi.21738
PG 10
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 198GT
UT WOS:000322911100005
PM 23740720
ER
PT J
AU Monzack, EL
Cunningham, LL
AF Monzack, Elyssa L.
Cunningham, Lisa L.
TI Lead roles for supporting actors: Critical functions of inner ear
supporting cells
SO HEARING RESEARCH
LA English
DT Review
ID AVIAN AUDITORY EPITHELIUM; SENSORY HAIR-CELLS; GUINEA-PIG COCHLEA;
GLUTAMATE-ASPARTATE TRANSPORTER; SPIRAL GANGLION NEURONS; LATERAL-LINE
SYSTEM; CHICK COCHLEA; ACOUSTIC TRAUMA; MAMMALIAN COCHLEA; PRIMARY
PHAGOCYTOSIS
AB Many studies that aim to investigate the underlying mechanisms of hearing loss or balance disorders focus on the hair cells and spiral ganglion neurons of the inner ear. Fewer studies have examined the supporting cells that contact both of these cell types in the cochlea and vestibular end organs. While the roles of supporting cells are still being elucidated, emerging evidence indicates that they serve many functions vital to maintaining healthy populations of hair cells and spiral ganglion neurons. Here we review recent studies that highlight the critical roles supporting cells play in the development, function, survival, death, phagocytosis, and regeneration of other cell types within the inner ear. Many of these roles have also been described for glial cells in other parts of the nervous system, and lessons from these other systems continue to inform our understanding of supporting cell functions.
This article is part of a Special Issue entitled "Annual Reviews 2013". Published by Elsevier B.V.
C1 [Monzack, Elyssa L.; Cunningham, Lisa L.] Natl Inst Deafness & Other Commun Disorders, Rockville, MD 20850 USA.
RP Cunningham, LL (reprint author), 5 Res Court,Room 2A-03, Rockville, MD 20850 USA.
EM elyssa.monzack@nih.gov; lisa.cunningham@nih.gov
FU NIDCD Division of Intramural Research
FX The authors would like to thank Dr. Doris Wu, Dr. Matthew Kelley, Dr.
Meghan Drummond, and Dr. Jonathan Bird for their helpful comments and
suggestions on the manuscript. The authors are also grateful to Dr.
Jonathan Gale for many thoughtful conversations about supporting cells
as well as constructive notes on the development of the text and figures
of this manuscript. This work was supported by the NIDCD Division of
Intramural Research.
NR 140
TC 25
Z9 26
U1 2
U2 16
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-5955
J9 HEARING RES
JI Hear. Res.
PD SEP
PY 2013
VL 303
SI SI
BP 20
EP 29
DI 10.1016/j.heares.2013.01.008
PG 10
WC Audiology & Speech-Language Pathology; Neurosciences;
Otorhinolaryngology
SC Audiology & Speech-Language Pathology; Neurosciences & Neurology;
Otorhinolaryngology
GA 200TS
UT WOS:000323094400003
PM 23347917
ER
PT J
AU Moseman, EA
McGavern, DB
AF Moseman, E. Ashley
McGavern, Dorian B.
TI The great balancing act: regulation and fate of antiviral T-cell
interactions
SO IMMUNOLOGICAL REVIEWS
LA English
DT Review
DE T cells; cytotoxic T cells; viral infection; neuroimmunology; in vivo
imaging; immunotherapies
ID LYMPHOCYTIC CHORIOMENINGITIS VIRUS; CENTRAL-NERVOUS-SYSTEM; PERSISTENT
VIRAL-INFECTION; IMMUNOLOGICAL SYNAPSE FORMATION; BLOOD-BRAIN-BARRIER;
PRESENTING B-CELLS; MHC CLASS-I; DENDRITIC CELLS; LYMPH-NODES;
IMMUNE-RESPONSES
AB The fate of T lymphocytes revolves around a continuous stream of interactions between the T-cell receptor (TCR) and peptide-major histocompatibility complex (MHC) molecules. Beginning in the thymus and continuing into the periphery, these interactions, refined by accessory molecules, direct the expansion, differentiation, and function of T-cell subsets. The cellular context of T-cell engagement with antigen-presenting cells, either in lymphoid or non-lymphoid tissues, plays an important role in determining how these cells respond to antigen encounters. CD8(+) T cells are essential for clearance of a lymphocytic choriomeningitis virus (LCMV) infection, but the virus can present a number of unique challenges that antiviral T cells must overcome. Peripheral LCMV infection can lead to rapid cytolytic clearance or chronic viral persistence; central nervous system infection can result in T-cell-dependent fatal meningitis or an asymptomatic carrier state amenable to immunotherapeutic clearance. These diverse outcomes all depend on interactions that require TCR engagement of cognate peptide-MHC complexes. In this review, we explore the diversity in antiviral T-cell behaviors resulting from TCR engagement, beginning with an overview of the immunological synapse and progressing to regulators of TCR signaling that shape the delicate balance between immunopathology and viral clearance.
C1 [Moseman, E. Ashley; McGavern, Dorian B.] NINDS, NIH, Bethesda, MD 20892 USA.
RP McGavern, DB (reprint author), NINDS, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM mcgavernd@mail.nih.gov
OI McGavern, Dorian/0000-0001-9568-545X
FU National Institutes of Health (NIH)
FX This study was supported by the National Institutes of Health (NIH)
intramural program. The authors have no conflicts of interest to
declare.
NR 171
TC 7
Z9 7
U1 0
U2 17
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0105-2896
J9 IMMUNOL REV
JI Immunol. Rev.
PD SEP
PY 2013
VL 255
IS 1
SI SI
BP 110
EP 124
DI 10.1111/imr.12093
PG 15
WC Immunology
SC Immunology
GA 201OM
UT WOS:000323150900009
PM 23947351
ER
PT J
AU Graham, BS
AF Graham, Barney S.
TI Advances in antiviral vaccine development
SO IMMUNOLOGICAL REVIEWS
LA English
DT Review
DE viral immunity; vaccine development; monoclonal antibodies; neutralizing
antibody; structure-based vaccine design; vaccines
ID RESPIRATORY SYNCYTIAL VIRUS; INFLUENZA-A VIRUSES; MEMORY B-CELLS; GP120
ENVELOPE GLYCOPROTEIN; HUMAN MONOCLONAL-ANTIBODIES; X-RAY-DIFFRACTION;
NEUTRALIZING ANTIBODY; HIV-1 VACCINE; HUMAN-IMMUNOGLOBULIN; POTENT
NEUTRALIZATION
AB Antiviral vaccines have been the most successful biomedical intervention for preventing epidemic viral disease. Vaccination for smallpox in humans and rinderpest in cattle was the basis for disease eradication, and recent progress in polio eradication is promising. Although early vaccines were developed empirically by passage in live animals or eggs, more recent vaccines have been developed because of the advent of new technologies, particularly cell culture and molecular biology. Recent technological advances in gene delivery and expression, nanoparticles, protein manufacturing, and adjuvants have created the potential for new vaccine platforms that may provide solutions for vaccines against viral pathogens for which no interventions currently exist. In addition, the technological convergence of human monoclonal antibody isolation, structural biology, and high-throughput sequencing is providing new opportunities for atomic-level immunogen design. Selection of human monoclonal antibodies can identify immunodominant antigenic sites associated with neutralization and provide reagents for stabilizing and solving the structure of viral surface proteins. Understanding the structural basis for neutralization can guide selection of vaccine targets. Deep sequencing of the antibody repertoire and defining the ontogeny of the desired antibody responses can reveal the junctional recombination and somatic mutation requirements for B-cell recognition and affinity maturation. Collectively, this information will provide new strategic approaches for selecting vaccine antigens, formulations, and regimens. Moreover, it creates the potential for rational vaccine design and establishing a catalogue of vaccine technology platforms that would be effective against any given family or class of viral pathogens and improve our readiness to address new emerging viral threats.
C1 NIAID, NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
RP Graham, BS (reprint author), NIAID, NIH, Vaccine Res Ctr, 40 Convent Dr Bldg 40,Rm 2502, Bethesda, MD 20892 USA.
EM bgraham@nih.gov
FU National Institute of Allergy and Infectious Diseases
FX I thank Dr. Julie E. Ledgerwood and Dr. Kayvon Modjarrad for thoughtful
advice and suggestions. This study was supported by the intramural
funding from the National Institute of Allergy and Infectious Diseases.
The author has no conflicts of interest to declare.
NR 89
TC 10
Z9 11
U1 9
U2 90
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0105-2896
J9 IMMUNOL REV
JI Immunol. Rev.
PD SEP
PY 2013
VL 255
IS 1
SI SI
BP 230
EP 242
DI 10.1111/imr.12098
PG 13
WC Immunology
SC Immunology
GA 201OM
UT WOS:000323150900017
PM 23947359
ER
PT J
AU Minato, Y
Ghosh, A
Faulkner, WJ
Lind, EJ
Bartra, SS
Plano, GV
Jarrett, CO
Hinnebusch, BJ
Winogrodzki, J
Dibrov, P
Hase, CC
AF Minato, Yusuke
Ghosh, Amit
Faulkner, Wyatt J.
Lind, Erin J.
Bartra, Sara Schesser
Plano, Gregory V.
Jarrett, Clayton O.
Hinnebusch, B. Joseph
Winogrodzki, Judith
Dibrov, Pavel
Haese, Claudia C.
TI Na+/H+ Antiport Is Essential for Yersinia pestis Virulence
SO INFECTION AND IMMUNITY
LA English
DT Article
ID LOW-CALCIUM RESPONSE; ESCHERICHIA-COLI; VIBRIO-CHOLERAE; NHAB; PH;
RESISTANCE; HOMEOSTASIS; EXPRESSION; INHIBITORS; BACTERIA
AB Na+/H+ antiporters are ubiquitous membrane proteins that play a central role in the ion homeostasis of cells. In this study, we examined the possible role of Na+/H+ antiport in Yersinia pestis virulence and found that Y. pestis strains lacking the major Na+/H+ antiporters, NhaA and NhaB, are completely attenuated in an in vivo model of plague. The Y. pestis derivative strain lacking the nhaA and nhaB genes showed markedly decreased survival in blood and blood serum ex vivo. Complementation of either nhaA or nhaB in trans restored the survival of the Y. pestis nhaA nhaB double deletion mutant in blood. The nhaA nhaB double deletion mutant also showed inhibited growth in an artificial serum medium, Opti-MEM, and a rich LB-based medium with Na+ levels and pH values similar to those for blood. Taken together, these data strongly suggest that intact Na+/H+ antiport is indispensable for the survival of Y. pestis in the bloodstreams of infected animals and thus might be regarded as a promising noncanonical drug target for infections caused by Y. pestis and possibly for those caused by other blood-borne bacterial pathogens.
C1 [Minato, Yusuke; Ghosh, Amit; Lind, Erin J.; Haese, Claudia C.] Oregon State Univ, Coll Vet Med, Dept Biomed Sci, Corvallis, OR 97331 USA.
[Faulkner, Wyatt J.; Haese, Claudia C.] Oregon State Univ, Dept Microbiol, Coll Sci, Corvallis, OR 97331 USA.
[Bartra, Sara Schesser; Plano, Gregory V.] Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL 33136 USA.
[Jarrett, Clayton O.; Hinnebusch, B. Joseph] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Winogrodzki, Judith; Dibrov, Pavel] Univ Manitoba, Dept Microbiol, Winnipeg, MB R3T 2N2, Canada.
RP Hase, CC (reprint author), Oregon State Univ, Coll Vet Med, Dept Biomed Sci, Corvallis, OR 97331 USA.
EM hasec@science.oregonstate.edu
FU National Institutes of Health [AI-064190-02, AI039575]; NSERC; Natural
Sciences and Engineering Research Council of Canada; Division of
Intramural Research, NIAID, NIH
FX This research was supported by grants from the National Institutes of
Health to C. C. H. (AI-064190-02) and G. V. P (AI039575) and from NSERC,
the Natural Sciences and Engineering Research Council of Canada (to P.
D. and J.W.). B.J.H. was supported by the Division of Intramural
Research, NIAID, NIH.
NR 38
TC 13
Z9 13
U1 0
U2 20
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
J9 INFECT IMMUN
JI Infect. Immun.
PD SEP
PY 2013
VL 81
IS 9
BP 3163
EP 3172
DI 10.1128/IAI.00071-13
PG 10
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 201NM
UT WOS:000323148300011
PM 23774602
ER
PT J
AU Kabeiseman, EJ
Cichos, K
Hackstadt, T
Lucas, A
Moore, ER
AF Kabeiseman, Emily J.
Cichos, Kyle
Hackstadt, Ted
Lucas, Andrea
Moore, Elizabeth R.
TI Vesicle-Associated Membrane Protein 4 and Syntaxin 6 Interactions at the
Chlamydial Inclusion
SO INFECTION AND IMMUNITY
LA English
DT Article
ID TRANS-GOLGI NETWORK; ENDOGENOUSLY SYNTHESIZED SPHINGOMYELIN; TRACHOMATIS
INCLUSION; SNARE COMPLEX; CULTURED FIBROBLASTS; MICROTUBULE NETWORK;
ENDOCYTIC PATHWAY; PLASMA-MEMBRANE; INFECTED CELLS; RAB GTPASES
AB The predominant players in membrane fusion events are the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) family of proteins. We hypothesize that SNARE proteins mediate fusion events at the chlamydial inclusion and are important for chlamydial lipid acquisition. We have previously demonstrated that trans-Golgi SNARE syntaxin 6 localizes to the chlamydial inclusion. To investigate the role of syntaxin 6 at the chlamydial inclusion, we examined the localization and function of another trans-Golgi SNARE and syntaxin 6-binding partner, vesicle-associated membrane protein 4 (VAMP4), at the chlamydial inclusion. In this study, we demonstrate that syntaxin 6 and VAMP4 colocalize to the chlamydial inclusion and interact at the chlamydial inclusion. Furthermore, in the absence of VAMP4, syntaxin 6 is not retained at the chlamydial inclusion. Small interfering RNA (siRNA) knockdown of VAMP4 inhibited chlamydial sphingomyelin acquisition, correlating with a log decrease in infectious progeny. VAMP4 retention at the inclusion was shown to be dependent on de novo chlamydial protein synthesis, but unlike syntaxin 6, VAMP4 recruitment is observed in a species-dependent manner. Notably, VAMP4 knockdown inhibits sphingomyelin trafficking only to inclusions in which it localizes. These data support the hypothesis that VAMP proteins play a central role in mediating eukaryotic vesicular interactions at the chlamydial inclusion and, thus, support chlamydial lipid acquisition and chlamydial development.
C1 [Kabeiseman, Emily J.; Cichos, Kyle; Lucas, Andrea; Moore, Elizabeth R.] Univ S Dakota, Div Basic Biomed Sci, Sanford Sch Med, Vermillion, SD 57069 USA.
[Hackstadt, Ted] NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, Rocky Mt Labs, Hamilton, MT USA.
RP Moore, ER (reprint author), Univ S Dakota, Div Basic Biomed Sci, Sanford Sch Med, Vermillion, SD 57069 USA.
EM Lisa.Moore@usd.edu
FU NIAID [1 K22 AI089856-01A1]; USD/SSOM/BBS; NIAID/NIH
FX This work was supported by an NIAID K22 award (1 K22 AI089856-01A1) and
USD/SSOM/BBS start-up funds both awarded to E.R.M. and an award from the
Intramural Research Program at NIAID/NIH to T.H.
NR 70
TC 7
Z9 7
U1 0
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
J9 INFECT IMMUN
JI Infect. Immun.
PD SEP
PY 2013
VL 81
IS 9
BP 3326
EP 3337
DI 10.1128/IAI.00584-13
PG 12
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 201NM
UT WOS:000323148300026
PM 23798538
ER
PT J
AU Kuhar, DT
Henderson, DK
Struble, KA
Heneine, W
Thomas, V
Cheever, LW
Gomaa, A
Panlilio, AL
AF Kuhar, David T.
Henderson, David K.
Struble, Kimberly A.
Heneine, Walid
Thomas, Vasavi
Cheever, Laura W.
Gomaa, Ahmed
Panlilio, Adelisa L.
CA US Public Hlth Serv Working Grp
TI Updated US Public Health Service Guidelines for the Management of
Occupational Exposures to Human Immunodeficiency Virus and
Recommendations for Postexposure Prophylaxis
SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY
LA English
DT Article
ID TO-CHILD TRANSMISSION; PRIOR ANTIRETROVIRAL THERAPY; CARE WORKERS;
HIV-INFECTION; NEEDLESTICK INJURY; HUMAN BITE; TYPE-1 INFECTION;
LACTIC-ACIDOSIS; PREGNANCY; RISK
AB This report updates US Public Health Service recommendations for the management of healthcare personnel (HCP) who experience occupational exposure to blood and/or other body fluids that might contain human immunodeficiency virus (HIV). Although the principles of exposure management remain unchanged, recommended HIV postexposure prophylaxis (PEP) regimens and the duration of HIV follow-up testing for exposed personnel have been updated. This report emphasizes the importance of primary prevention strategies, the prompt reporting and management of occupational exposures, adherence to recommended HIV PEP regimens when indicated for an exposure, expert consultation in management of exposures, follow-up of exposed HCP to improve adherence to PEP, and careful monitoring for adverse events related to treatment, as well as for virologic, immunologic, and serologic signs of infection. To ensure timely postexposure management and administration of HIV PEP, clinicians should consider occupational exposures as urgent medical concerns, and institutions should take steps to ensure that staff are aware of both the importance of and the institutional mechanisms available for reporting and seeking care for such exposures. The following is a summary of recommendations: (1) PEP is recommended when occupational exposures to HIV occur; (2) the HIV status of the exposure source patient should be determined, if possible, to guide need for HIV PEP; (3) PEP medication regimens should be started as soon as possible after occupational exposure to HIV, and they should be continued for a 4-week duration; (4) new recommendationPEP medication regimens should contain 3 (or more) antiretroviral drugs (listed in Appendix A) for all occupational exposures to HIV; (5) expert consultation is recommended for any occupational exposures to HIV and at a minimum for situations described in Box 1; (6) close follow-up for exposed personnel (Box 2) should be provided that includes counseling, baseline and follow-up HIV testing, and monitoring for drug toxicity; follow-up appointments should begin within 72 hours of an HIV exposure; and (7) new recommendationif a newer fourth-generation combination HIV p24 antigen--HIV antibody test is utilized for follow-up HIV testing of exposed HCP, HIV testing may be concluded 4 months after exposure (Box 2); if a newer testing platform is not available, follow-up HIV testing is typically concluded 6 months after an HIV exposure.
C1 [Kuhar, David T.; Panlilio, Adelisa L.] Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30333 USA.
[Henderson, David K.] NIH, Off Deputy Director Clin Care, Ctr Clin, Bethesda, MD 20892 USA.
[Struble, Kimberly A.] US FDA, Div Antiviral Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Heneine, Walid; Thomas, Vasavi] Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Natl Ctr HIV AIDS Viral Hepatitis STD & TB Preven, Atlanta, GA USA.
[Cheever, Laura W.] US Hlth Resources & Serv Adm, HIV AIDS Bur, Rockville, MD 20857 USA.
[Gomaa, Ahmed] NIOSH, Div Surveillance Hazard Evaluat & Hlth Studies, Ctr Dis Control & Prevent, Cincinnati, OH 45226 USA.
RP Kuhar, DT (reprint author), Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30333 USA.
FU Bristol-Myers Squibb; Janssen; Merck; ViiV; GlaxoSmithKline; Gilead
FX The expert panel consultants report the following competing interests:
J.A. has a board membership with and has received funding from
Bristol-Myers Squibb, Janssen, Merck, and ViiV; J.E. has consulted for
Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Janssen, Merck, and ViiV
and has received grant funding from Bristol-Myers Squibb,
GlaxoSmithKline, Merck, and ViiV; M. S. S. has consulted for
Bristol-Myers Squibb, Gilead, Janssen, Merck, and ViiV and has received
grant funding from Bristol-Myers Squibb, Gilead, Merck, and ViiV; M. L.
T. owns Merck stock. All other authors report no conflicts of interest
relevant to this article.
NR 76
TC 98
Z9 102
U1 2
U2 19
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0899-823X
J9 INFECT CONT HOSP EP
JI Infect. Control Hosp. Epidemiol.
PD SEP 1
PY 2013
VL 34
IS 9
BP 875
EP 892
DI 10.1086/672271
PG 18
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 195LD
UT WOS:000322702900001
PM 23917901
ER
PT J
AU Li, QTQ
Lee, RX
Liang, HS
Wang, GD
Li, JLM
Zhong, YH
Reed, E
AF Li, Quentin Q.
Lee, Rebecca X.
Liang, Huasheng
Wang, Gangduo
Li, Jueli M.
Zhong, Yuhua
Reed, Eddie
TI beta-Elemene enhances susceptibility to cisplatin in resistant ovarian
carcinoma cells via downregulation of ERCC-1 and XIAP and inactivation
of JNK
SO INTERNATIONAL JOURNAL OF ONCOLOGY
LA English
DT Article
DE apoptosis; cisplatin resistance; beta-elemene; Chinese medicine; ovarian
cancer; excision repair cross-complementation group-1; X-linked
inhibitor of apoptosis protein; c-Jun NH2-terminal kinase
ID NUCLEOTIDE EXCISION-REPAIR; MESSENGER-RNA EXPRESSION; PLATINUM-DNA
ADDUCT; LUNG-CANCER CELLS; SOLID TUMOR-CELLS; INDUCED APOPTOSIS;
PROSTATE-CANCER; ANTICANCER CHEMOTHERAPY; SIGNAL-TRANSDUCTION; SYNTHETIC
ANALOGS
AB beta-Elemene is a promising new plant-derived drug with broad-spectrum anticancer activity. It also increases cisplatin cytotoxicity and enhances cisplatin sensitivity in resistant human carcinoma cells. However, little is known about the mechanism of its action. To explore the potential therapeutic application of beta-elemene as a drug-resistance modulator, this study investigated the underlying mechanism of beta-elemene activity in cisplatin-resistant ovarian cancer cells. beta-Elemene enhanced cisplatin sensitivity to a much greater extent in chemoresistant A2780/CP70 and MCAS human ovarian carcinoma cells compared to the chemosensitive parental cell line A2780. The dose-modifying factors for cisplatin were between 35 and 60 for A2780/CP70 cells and between 1.6 and 2.5 for A2780 cells. In the cisplatin-resistant ovarian carcinoma cells, beta-elemene abrogated cisplatin-induced expression of excision repair cross-complementation group-1 (ERCC-1), a marker gene in the nucleotide excision repair pathway that repairs cisplatin-caused DNA damage. In addition, beta-elemene not only reduced the level of X-linked inhibitor of apoptosis protein (XIAP), but also downregulated cisplatin-mediated XIAP expression in chemoresistant cells. Furthermore, beta-elemene blocked the cisplatin-stimulated increase in the level of phosphorylated c-Jun NH2-terminal kinase (JNK) in these cells. These novel findings suggest that the beta-elemene enhancement of cisplatin sensitivity in human chemoresistant ovarian cancer cells is mediated at least in part through the impairment of DNA repair activity and the activation of apoptotic signaling pathways, thereby making resistant ovarian cancer cells susceptible to cisplatin-induced cell death.
C1 [Liang, Huasheng; Zhong, Yuhua] Beihai Inst Endocrine & Metab Dis, Beihai 536000, Guangxi, Peoples R China.
[Li, Quentin Q.; Reed, Eddie] NIH, Bethesda, MD 20892 USA.
[Li, Quentin Q.; Lee, Rebecca X.; Wang, Gangduo; Reed, Eddie] W Virginia Univ, Sch Med, Morgantown, WV 26506 USA.
[Li, Jueli M.] Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA.
RP Li, QTQ (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM liquenti@mail.nih.gov; flowchaos@aliyun.com
FU Natural Science Foundation of Science and Technology Department of
Guangxi Province [0991294]; Guangxi Scientific Research and
Technological Development Program [200901059]; National Institutes of
Health [P20RR16440-010003, P20RR16440-020003, P20RR16440-030003,
P20RR16440-040003]; West Virginia University School of Medicine Research
Grant
FX This publication was made possible by grants from the Natural Science
Foundation of Science and Technology Department of Guangxi Province (no.
0991294); the Guangxi Scientific Research and Technological Development
Program (no. 200901059); and by grants from the National Institutes of
Health (nos. P20RR16440-010003, P20RR16440-020003, P20RR16440-030003,
P20RR16440-040003) and a West Virginia University School of Medicine
Research Grant (to Q.Q.L.).
NR 73
TC 17
Z9 19
U1 0
U2 12
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1019-6439
J9 INT J ONCOL
JI Int. J. Oncol.
PD SEP
PY 2013
VL 43
IS 3
BP 721
EP 728
DI 10.3892/ijo.2013.1996
PG 8
WC Oncology
SC Oncology
GA 190XD
UT WOS:000322375900005
PM 23817665
ER
PT J
AU Iranzo, J
Lobkovsky, AE
Wolf, YI
Koonin, EV
AF Iranzo, Jaime
Lobkovsky, Alexander E.
Wolf, Yuri I.
Koonin, Eugene V.
TI Evolutionary Dynamics of the Prokaryotic Adaptive Immunity System
CRISPR-Cas in an Explicit Ecological Context
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID NATURAL MICROBIAL COMMUNITIES; SULFATE-REDUCING BACTERIA; WADDEN SEA;
STREPTOCOCCUS-THERMOPHILUS; VERTICAL-DISTRIBUTION; POPULATION-DYNAMICS;
DEFENSE SYSTEMS; BLACK SMOKER; DIVERSITY; RNA
AB A stochastic, agent-based mathematical model of the coevolution of the archaeal and bacterial adaptive immunity system, CRISPR-Cas, and lytic viruses shows that CRISPR-Cas immunity can stabilize the virus-host coexistence rather than leading to the extinction of the virus. In the model, CRISPR-Cas immunity does not specifically promote viral diversity, presumably because the selection pressure on each single proto-spacer is too weak. However, the overall virus diversity in the presence of CRISPR-Cas grows due to the increase of the host and, accordingly, the virus population size. Above a threshold value of total viral diversity, which is proportional to the viral mutation rate and population size, the CRISPR-Cas system becomes ineffective and is lost due to the associated fitness cost. Our previous modeling study has suggested that the ubiquity of CRISPR-Cas in hyperthermophiles, which contrasts its comparative low prevalence in mesophiles, is due to lower rates of mutation fixation in thermal habitats. The present findings offer a complementary, simpler perspective on this contrast through the larger population sizes of mesophiles compared to hyperthermophiles, because of which CRISPR-Cas can become ineffective in mesophiles. The efficacy of CRISPR-Cas sharply increases with the number of proto-spacers per viral genome, potentially explaining the low information content of the proto-spacer-associated motif (PAM) that is required for spacer acquisition by CRISPR-Cas because a higher specificity would restrict the number of spacers available to CRISPR-Cas, thus hampering immunity. The very existence of the PAM might reflect the tradeoff between the requirement of diverse spacers for efficient immunity and avoidance of autoimmunity.
C1 [Iranzo, Jaime] INTA CSIC, Ctr Astrobiol, Madrid, Spain.
[Lobkovsky, Alexander E.; Wolf, Yuri I.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
EM koonin@ncbi.nlm.nih.gov
RI Iranzo, Jaime/H-5197-2011
OI Iranzo, Jaime/0000-0002-4538-7726
FU Comunidad de Madrid [MODELICO S2009/ESP-1691]; Spanish MINECO
[FIS2011-27569]; U.S. Department of Health and Human Services
FX J.I. is supported by Comunidad de Madrid through a research grant and
project MODELICO S2009/ESP-1691 and Spanish MINECO through project
FIS2011-27569.; A.E.L., Y.I.W., and E.V.K. are supported by intramural
funds from the U.S. Department of Health and Human Services (to the
National Library of Medicine).
NR 88
TC 15
Z9 15
U1 0
U2 35
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0021-9193
J9 J BACTERIOL
JI J. Bacteriol.
PD SEP
PY 2013
VL 195
IS 17
BP 3834
EP 3844
DI 10.1128/JB.00412-13
PG 11
WC Microbiology
SC Microbiology
GA 200DM
UT WOS:000323047900005
PM 23794616
ER
PT J
AU Cunnington, AJ
Bretscher, MT
Nogaro, SI
Riley, EM
Walther, M
AF Cunnington, Aubrey J.
Bretscher, Michael T.
Nogaro, Sarah I.
Riley, Eleanor M.
Walther, Michael
TI Comparison of parasite sequestration in uncomplicated and severe
childhood Plasmodium falciparum malaria
SO JOURNAL OF INFECTION
LA English
DT Article
DE Cerebral malaria; Microcirculation; Lactic acid; Sequestration; HRP2;
Anaemia; Parasite Biomass
ID CEREBRAL MALARIA; AFRICAN CHILDREN; RANDOMIZED-TRIAL; ADJUNCTIVE
THERAPY; MALAWIAN CHILDREN; PATHOGENESIS; MANAGEMENT; MORTALITY; AGE;
PATHOPHYSIOLOGY
AB Objectives: To determine whether sequestration of parasitized red blood cells differs between children with uncomplicated and severe Plasmodium falciparum malaria.
Methods: We quantified circulating-, total-and sequestered-parasite biomass, using a mathematical model based on plasma concentration of P. falciparum histidine rich protein 2, in Gambian children with severe (n = 127) and uncomplicated (n = 169) malaria.
Results: Circulating-and total-, but not sequestered-, parasite biomass estimates were significantly greater in children with severe malaria than in those with uncomplicated malaria. Sequestered biomass estimates in children with hyperlactataemia or prostration were similar to those in uncomplicated malaria, whereas sequestered biomass was higher in patients with severe anaemia, and showed a trend to higher values in cerebral malaria and fatal cases. Blood lactate concentration correlated with circulating-and total-, but not sequestered parasite biomass. These findings were robust after controlling for age, prior antimalarial treatment and clonality of infection, and over a realistic range of variation in model parameters.
Conclusion: Extensive sequestration is not a uniform requirement for severe paediatric malaria. The pathophysiology of hyperlactataemia and prostration appears to be unrelated to sequestered parasite biomass. Different mechanisms may underlie different severe malaria syndromes, and different therapeutic strategies may be required to improve survival. Published by Elsevier Ltd on behalf of The British Infection Association.
C1 [Cunnington, Aubrey J.; Bretscher, Michael T.; Nogaro, Sarah I.; Riley, Eleanor M.] Univ London London Sch Hyg & Trop Med, Dept Immunol & Infect, Fac Infect & Trop Dis, London WC1E 7HT, England.
[Cunnington, Aubrey J.; Nogaro, Sarah I.; Walther, Michael] Med Res Council UK Labs, Banjul, Gambia.
[Cunnington, Aubrey J.] Univ London Imperial Coll Sci Technol & Med, Dept Med, Paediat Sect, London W2 1PG, England.
[Walther, Michael] NIAID, Immune Regulat Sect, Lab Malaria Immunol & Vaccinol, Div Intramural Res,NIH, Rockville, MD 20852 USA.
RP Walther, M (reprint author), NIAID, Immune Regulat Sect, Lab Malaria Immunol & Vaccinol, Div Intramural Res,NIH, Twinbrook 2 Rm 239 A,12441 Parklawn Dr, Rockville, MD 20852 USA.
EM Michael.Walther@nih.gov
RI Riley, Eleanor/C-8960-2013;
OI Riley, Eleanor/0000-0003-3447-3570; Cunnington,
Aubrey/0000-0002-1305-3529
FU Medical Research Council, UK [G0701427]
FX This work was supported by core funding from the Medical Research
Council, UK to the malaria research programme, and a Medical Research
Council, UK, clinical research training fellowship [G0701427 to A.J.C.].
NR 57
TC 11
Z9 11
U1 0
U2 13
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0163-4453
J9 J INFECTION
JI J. Infect.
PD SEP
PY 2013
VL 67
IS 3
BP 220
EP 230
DI 10.1016/j.jinf.2013.04.013
PG 11
WC Infectious Diseases
SC Infectious Diseases
GA 195XO
UT WOS:000322737300007
PM 23623771
ER
PT J
AU Kumar, NP
Sridhar, R
Banurekha, VV
Jawahar, MS
Nutman, TB
Babu, S
AF Kumar, Nathella Pavan
Sridhar, Rathinam
Banurekha, Vaithilingam V.
Jawahar, Mohideen S.
Nutman, Thomas B.
Babu, Subash
TI Expansion of Pathogen-Specific T-Helper 1 and T-Helper 17 Cells in
Pulmonary Tuberculosis With Coincident Type 2 Diabetes Mellitus
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE T cells; bacterial; cytokines; tuberculosis; diabetes mellitus
ID MYCOBACTERIUM-TUBERCULOSIS; INTERFERON-GAMMA; IMMUNE-RESPONSES;
IFN-GAMMA; MICE; DISEASE; RESISTANCE; CHALLENGE; INFECTION; SYSTEM
AB Background. Type 2 diabetes mellitus (DM) is a major risk factor for the development of active pulmonary tuberculosis, although the immunological mechanisms underlying this interaction remain unexplored. The influence of poorly controlled diabetes on pathogen-specific T-helper 1 (Th1) and T-helper 17 (Th17) responses have not been examined.
Methods. To identify the role of Th1 and Th17 cells in tuberculosis with coincident DM, we examined mycobacteria-specific immune responses in the whole blood of individuals who had tuberculosis with DM and compared them to those in individuals who had tuberculosis without DM.
Results. Tuberculosis coincident with DM is characterized by elevated frequencies of monofunctional and dual-functional CD4(+) Th1 cells following Mycobacterium tuberculosis antigen stimulation and elevated frequencies of Th17 subsets at both baseline and following antigen stimulation. This was associated with increased systemic (plasma) levels of both Th1 and Th17 cytokines and decreased baseline frequencies of natural regulatory T cells but not interleukin 10 or transforming growth factor beta.
Conclusions. Therefore, our data reveal that tuberculosis in persons with DM is characterized by elevated frequencies of Th1 and Th17 cells, indicating that DM is associated with an alteration in the immune response to tuberculosis, leading to a biased induction of Th1- and Th17-mediated cellular responses and likely contributing to increased immune pathology in M. tuberculosis infection.
C1 [Kumar, Nathella Pavan; Babu, Subash] Natl Inst Hlth Int Ctr Excellence Res, Madras, Tamil Nadu, India.
[Kumar, Nathella Pavan; Banurekha, Vaithilingam V.; Jawahar, Mohideen S.] Natl Inst Res TB, Madras, Tamil Nadu, India.
[Sridhar, Rathinam] Govt Stanley Med Hosp, Madras, Tamil Nadu, India.
[Nutman, Thomas B.; Babu, Subash] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Babu, Subash] SAIC Frederick, Frederick, MD USA.
RP Babu, S (reprint author), Natl Inst Res TB, NIH ICER, Madras, Tamil Nadu, India.
EM sbabu@mail.nih.gov
FU Intramural Research Program of the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX This work was supported by the Intramural Research Program of the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health.
NR 34
TC 36
Z9 38
U1 0
U2 9
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD SEP 1
PY 2013
VL 208
IS 5
BP 739
EP 748
DI 10.1093/infdis/jit241
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 198YB
UT WOS:000322958900006
PM 23715661
ER
PT J
AU Kalams, SA
Parker, SD
Elizaga, M
Metch, B
Edupuganti, S
Hural, J
De Rosa, S
Carter, DK
Rybczyk, K
Frank, I
Fuchs, J
Koblin, B
Kim, DH
Joseph, P
Keefer, MC
Baden, LR
Eldridge, J
Boyer, J
Sherwat, A
Cardinali, M
Allen, M
Pensiero, M
Butler, C
Khan, AS
Yan, J
Sardesai, NY
Kublin, JG
Weiner, DB
AF Kalams, Spyros A.
Parker, Scott D.
Elizaga, Marnie
Metch, Barbara
Edupuganti, Srilatha
Hural, John
De Rosa, Stephen
Carter, Donald K.
Rybczyk, Kyle
Frank, Ian
Fuchs, Jonathan
Koblin, Beryl
Kim, Denny H.
Joseph, Patrice
Keefer, Michael C.
Baden, Lindsey R.
Eldridge, John
Boyer, Jean
Sherwat, Adam
Cardinali, Massimo
Allen, Mary
Pensiero, Michael
Butler, Chris
Khan, Amir S.
Yan, Jian
Sardesai, Niranjan Y.
Kublin, James G.
Weiner, David B.
CA NIAID HIV Vaccine Trials Network
TI Safety and Comparative Immunogenicity of an HIV-1 DNA Vaccine in
Combination with Plasmid Interleukin 12 and Impact of Intramuscular
Electroporation for Delivery
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE vaccination; electroporation; plasmid cytokine adjuvant
ID T-CELL RESPONSES; IN-VIVO ELECTROPORATION; IMMUNE-RESPONSES; RHESUS
MACAQUES; CANDIDATE VACCINE; PHASE-1 SAFETY; GROWTH-FACTOR; CYTOKINE;
VIREMIA; IL-12
AB Background. DNA vaccines have been very poorly immunogenic in humans but have been an effective priming modality in prime-boost regimens.
Methods to increase the immunogenicity of DNA vaccines are needed. Methods. HIV Vaccine Trials Network (HVTN) studies 070 and 080 were multicenter, randomized, clinical trials. The human immunodeficiency virus type 1 (HIV-1) PENNVAX(R)-B DNA vaccine (PV) is a mixture of 3 expression plasmids encoding HIV-1 Clade B Env, Gag, and Pol. The interleukin 12 (IL-12) DNA plasmid expresses human IL-12 proteins p35 and p40. Study subjects were healthy HIV-1-uninfected adults 18-50 years old. Four intramuscular vaccinations were given in HVTN 070, and 3 intramuscular vaccinations were followed by electroporation in HVTN 080. Cellular immune responses were measured by intracellular cytokine staining after stimulation with HIV-1 peptide pools.
Results. Vaccination was safe and well tolerated. Administration of PV plus IL-12 with electroporation had a significant dose-sparing effect and provided immunogenicity superior to that observed in the trial without electroporation, despite fewer vaccinations. A total of 71.4% of individuals vaccinated with PV plus IL-12 plasmid with electroporation developed either a CD4(+) or CD8(+) T-cell response after the second vaccination, and 88.9% developed a CD4(+) or CD8(+) T-cell response after the third vaccination.
Conclusions. Use of electroporation after PV administration provided superior immunogenicity than delivery without electroporation. This study illustrates the power of combined DNA approaches to generate impressive immune responses in humans.
C1 [Kalams, Spyros A.; Rybczyk, Kyle] Vanderbilt Univ, Div Infect Dis, Dept Med, Sch Med, Nashville, TN 37232 USA.
[Kalams, Spyros A.; Rybczyk, Kyle] Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA.
[Parker, Scott D.] Univ Alabama Birmingham, Div Infect Dis, Dept Med, Med Ctr, Birmingham, AL USA.
[Elizaga, Marnie; Metch, Barbara; Hural, John; De Rosa, Stephen; Carter, Donald K.; Kublin, James G.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA.
[Edupuganti, Srilatha] Emory Univ, Atlanta, GA 30322 USA.
[Frank, Ian] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Boyer, Jean; Weiner, David B.] Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA.
[Khan, Amir S.; Yan, Jian; Sardesai, Niranjan Y.] Inovio Pharmaceut, Blue Bell, PA USA.
[Fuchs, Jonathan] San Francisco Dept Hlth, San Francisco, CA USA.
[Koblin, Beryl] New York Blood Ctr, Lab Infect Dis Prevent, New York, NY 10021 USA.
[Keefer, Michael C.] Univ Rochester, Sch Med & Dent, New York, NY USA.
[Eldridge, John] Profectus BioSci, Tarrytown, NY USA.
[Kim, Denny H.] Astellas Pharma US, Northbrook, IL USA.
[Joseph, Patrice] Grp Haitien Etud Sarcome Kaposi & Infect Opportun, Port Au Prince, Haiti.
[Baden, Lindsey R.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA.
[Sherwat, Adam; Cardinali, Massimo; Allen, Mary; Pensiero, Michael; Butler, Chris] NIAID, Bethesda, MD 20892 USA.
RP Kalams, SA (reprint author), Vanderbilt Univ, Med Ctr, 1161 21st Ave South,MCN A2207, Nashville, TN 37232 USA.
EM s.kalams@vanderbilt.edu
RI Weiner, David/H-8579-2014;
OI Allen, Mary/0000-0001-8163-0714
FU National Institute of Allergy and Infectious Diseases of the National
Institutes of Health [UM1 AI068614, UM1 AI068635, UM1 AI068618, UM1
AI069452, UM1 AI069418, UM1 AI069511, UM1 AI069421, UM1 AI069412, UM1
AI069470, UM1 AI069439, UM1 AI069534, UM1 AI069496, P01-AI071739]; HVDDT
[HHSN272200800063C]; CTSA [UL1TR000445]
FX This work was supported by the National Institute of Allergy and
Infectious Diseases of the National Institutes of Health (grants UM1
AI068614 [to the HVTN Core FHCRC], UM1 AI068635 [to SCHARP], UM1
AI068618 [to the HVTN Laboratory program FHCRC], UM1 AI069452 [to UAB],
UM1 AI069418 [to Emory], UM1 AI069511 [to Rochester], UM1 AI069421 [to
GHESKIO], UM1 AI069412 [to BWH], UM1 AI069470 [to the New York Blood
Center-Bronx, NY Blood Center-Union Square, and Columbia University],
UM1 AI069439 [to Vanderbilt], UM1 AI069534 [to UPENN], UM1 AI069496 [to
SFDPH], P01-AI071739 [to Penn], HVDDT contract HHSN272200800063C [to
Inovio], and CTSA award no. UL1TR000445 to Vanderbilt.).
NR 44
TC 60
Z9 60
U1 0
U2 10
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD SEP 1
PY 2013
VL 208
IS 5
BP 818
EP 829
DI 10.1093/infdis/jit236
PG 12
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 198YB
UT WOS:000322958900014
PM 23840043
ER
PT J
AU Tobian, AAR
Grabowski, MK
Serwadda, D
Newell, K
Ssebbowa, P
Franco, V
Nalugoda, F
Wawer, MJ
Gray, RH
Quinn, TC
Reynolds, SJ
AF Tobian, Aaron A. R.
Grabowski, Mary K.
Serwadda, David
Newell, Kevin
Ssebbowa, Paschal
Franco, Veronica
Nalugoda, Fred
Wawer, Maria J.
Gray, Ronald H.
Quinn, Thomas C.
Reynolds, Steven J.
CA Rakai Hlth Sci Program
TI Reactivation of Herpes Simplex Virus Type 2 After Initiation of
Antiretroviral Therapy
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE herpes simplex virus type 2 (HSV-2); human immunodeficiency virus (HIV);
immune reconstitution inflammatory syndrome (IRIS); acyclovir;
reactivation; Uganda
ID RECONSTITUTION INFLAMMATORY SYNDROME; PLACEBO-CONTROLLED TRIAL; GENITAL
ULCER DISEASE; HIV-1 ACQUISITION; DOUBLE-BLIND; INFECTION; WOMEN;
UGANDA; RAKAI; MEN
AB Background. The association between initiation of antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection and possible herpes simplex virus type 2 (HSV-2) shedding and genital ulcer disease (GUD) has not been evaluated.
Methods. GUD and vaginal HSV-2 shedding were evaluated among women coinfected with HIV and HSV-2 (n = 440 for GUD and n = 96 for HSV-2 shedding) who began ART while enrolled in a placebo-controlled trial of HSV-2 suppression with acyclovir in Rakai, Uganda. Monthly vaginal swabs were tested for HSV-2 shedding, using a real-time quantitative polymerase chain reaction assay. Prevalence risk ratios (PRRs) of GUD were estimated using log binomial regression. Random effects logistic regression was used to estimate odds ratios (ORs) of HSV-2 shedding.
Results. Compared with pre-ART values, GUD prevalence increased significantly within the first 3 months after ART initiation (adjusted PRR, 1.94; 95% confidence interval [CI], 1.04-3.62) and returned to baseline after 6 months of ART (adjusted PRR, 0.80; 95% CI,.35-1.80). Detection of HSV-2 shedding was highest in the first 3 months after ART initiation (adjusted OR, 2.58; 95% CI, 1.48-4.49). HSV-2 shedding was significantly less common among women receiving acyclovir (adjusted OR, 0.13; 95% CI, .04-.41).
Conclusions. The prevalence of HSV-2 shedding and GUD increased significantly after ART initiation, possibly because of immune reconstitution inflammatory syndrome. Acyclovir significantly reduced both GUD and HSV-2 shedding and should be considered to mitigate these effects following ART initiation.
C1 [Tobian, Aaron A. R.] Johns Hopkins Univ, Dept Pathol, Sch Med, Baltimore, MD 21287 USA.
[Franco, Veronica; Quinn, Thomas C.; Reynolds, Steven J.] Johns Hopkins Univ, Dept Med, Sch Med, Baltimore, MD 21287 USA.
[Grabowski, Mary K.; Wawer, Maria J.; Gray, Ronald H.; Reynolds, Steven J.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD 21287 USA.
[Newell, Kevin] SAIC Frederick, Clin Res Directorate, Clin Monitoring Res Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Quinn, Thomas C.; Reynolds, Steven J.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Serwadda, David; Ssebbowa, Paschal; Nalugoda, Fred; Wawer, Maria J.; Gray, Ronald H.; Reynolds, Steven J.] Rakai Hlth Sci Program, Entebbe, Uganda.
[Serwadda, David] Makerere Univ, Inst Publ Hlth, Kampala, Uganda.
RP Tobian, AAR (reprint author), Johns Hopkins Univ, Dept Pathol, Carnegie 437,600 N Wolfe St, Baltimore, MD 21287 USA.
EM atobian1@jhmi.edu
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health (NIH); National
Cancer Institute, NIH [HHSN26 1200800001E]; NIH [1K23AI093152-01A1];
Doris Duke Charitable Foundation [22006.02]; [PO1 AI-30731-19]
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health (NIH; and in part by program project grant PO1 AI-30731-19); the
National Cancer Institute, NIH (contract HHSN26 1200800001E); the NIH
(grant 1K23AI093152-01A1 to A. A. R. T.); and the Doris Duke Charitable
Foundation (Clinician Scientist Development Award 22006.02 to A. A. R.
T.).
NR 34
TC 15
Z9 15
U1 0
U2 13
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD SEP 1
PY 2013
VL 208
IS 5
BP 839
EP 846
DI 10.1093/infdis/jit252
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 198YB
UT WOS:000322958900016
PM 23812240
ER
PT J
AU Muller, M
Jochemsen, HM
Visseren, FLJ
Grool, AM
Launer, LJ
van der Graaf, Y
Geerlings, MI
AF Muller, M.
Jochemsen, H. M.
Visseren, F. L. J.
Grool, A. M.
Launer, L. J.
van der Graaf, Y.
Geerlings, M. I.
CA SMART-Study Grp
TI Low blood pressure and antihypertensive treatment are independently
associated with physical and mental health status in patients with
arterial disease: the SMART study
SO JOURNAL OF INTERNAL MEDICINE
LA English
DT Article
DE antihypertensive treatment; blood pressure; cardiovascular disease;
mental health; physical health
ID QUALITY-OF-LIFE; UNITED-STATES; 2ND MANIFESTATIONS; DRUG-TREATMENT;
EPIC-NORFOLK; OLDER-ADULTS; HYPERTENSION; POPULATION; DEPRESSION;
MORTALITY
AB Objective. To investigate the independent effects of antihypertensive treatment and blood pressure (BP) levels on physical and mental health status in patients with arterial disease.
Design and setting. Cross-sectional analyses were conducted within the single-centre Secondary Manifestations of ARTerial disease (SMART) study, in a hospital care setting.
Subjects. A total of 5877 patients (mean age 57 years) with symptomatic and asymptomatic arterial disease underwent standardized vascular screening.
Main outcome measure. The primary outcome was self-rated physical and mental health assessed using the 36-item short-form health survey.
Results. In the total population, antihypertensive drug use and increased intensity of antihypertensive treatment were associated with poorer health status independent of important confounders including BP levels; adjusted mean differences [95% confidence interval (CI)] in physical and mental health between n = 0 and n >= 3 antihypertensives were -1.2 (-2.1; -0.3) and -3.5 (-4.4; -2.6), respectively. Furthermore, both lower systolic and lower diastolic BP levels were related to poorer physical and mental health status independent of antihypertensive treatment. Mean differences (95% CI) in physical and mental health status per SD decrease in systolic BP were -0.56 (-0.84; -0.27) and -0.32 (-0.61; -0.03) and per SD decrease in diastolic BP were -0.50 (-0.78; -0.23) and -0.08 (-0.36; 0.20), respectively. The association between low BP and poor health status was particularly present in patients with coronary artery disease.
Conclusions. In a population of patients with asymptomatic and symptomatic arterial disease, antihypertensive treatment and lower BP levels are independently associated with poorer self-rated physical and mental health. These findings suggest that different underlying mechanisms may explain these independent associations.
C1 [Muller, M.] Vrije Univ Amsterdam Med Ctr, Dept Internal Med, Amsterdam, Netherlands.
[Muller, M.; Jochemsen, H. M.; Grool, A. M.; van der Graaf, Y.; Geerlings, M. I.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
[Muller, M.; Launer, L. J.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA.
[Jochemsen, H. M.] Vrije Univ Amsterdam Med Ctr, Alzheimer Ctr, Amsterdam, Netherlands.
[Visseren, F. L. J.] Univ Med Ctr Utrecht, Dept Vasc Med, Utrecht, Netherlands.
[Grool, A. M.] Univ Med Ctr Utrecht, Dept Radiol, Utrecht, Netherlands.
RP Geerlings, MI (reprint author), Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
EM m.geerlings@umcutrecht.nl
FU Netherlands Organization for Scientific Research [904-65-095];
Internationale Stichting Alzheimer Onderzoek [09502]; Alzheimer
Nederland [WE. 15-2011-02]
FX We gratefully acknowledge the members of the SMART Study Group of the
University Medical Center Utrecht: A. Algra, MD, PhD, Julius Center for
Health Sciences and Primary Care and Rudolf Magnus Institute for
Neurosciences, Department of Neurology; P. A. Doevendans, MD, PhD,
Department of Cardiology; Y. van der Graaf, MD, PhD, D. E. Grobbee, MD,
PhD and G. E. H. M. Rutten, MD, PhD, Julius Center for Health Sciences
and Primary Care; L.J. Kappelle, MD, PhD, Department of Neurology; W. P.
Th.M. Mali, MD, PhD, Department of Radiology; F. L. Moll, MD, PhD,
Department of Vascular Surgery; and F.L.J. Visseren, MD, PhD, Department
of Vascular Medicine. This study was supported by a programme grant from
the Netherlands Organization for Scientific Research (project no.
904-65-095) and research grants from the Internationale Stichting
Alzheimer Onderzoek (project no. 09502) and Alzheimer Nederland (project
no. WE. 15-2011-02).
NR 32
TC 4
Z9 4
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0954-6820
J9 J INTERN MED
JI J. Intern. Med.
PD SEP
PY 2013
VL 274
IS 3
BP 241
EP 251
DI 10.1111/joim.12069
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 198FM
UT WOS:000322907600005
PM 23527863
ER
PT J
AU Segre, JA
AF Segre, Julia A.
TI What Does It Take to Satisfy Koch's Postulates Two Centuries Later?:
Microbial Genomics and Propionibacteria acnes
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Article
AB For two centuries, Koch's postulates have set the gold standard for establishing the microbiological etiology of infection and disease. Genomic sequencing now brings finer resolution to both bacterial strain variation and the host genetic state that may predispose to disease. In this issue of the JID, Fitz-Gibbons and colleagues present strain-based resolution of Propionibacterium acnes and its association with the common teenage malady acne vulgaris. Here I examine how Koch's postulates were envisioned and incorporate this finer resolution of both host and microbial states.
C1 NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
RP Segre, JA (reprint author), NHGRI, Genet & Mol Biol Branch, NIH, 49 Convent Dr,Bldg 49 Room 4A26, Bethesda, MD 20892 USA.
EM jsegre@nhgri.nih.gov
FU Intramural NIH HHS [ZIA HG000180-12]
NR 8
TC 6
Z9 6
U1 2
U2 21
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD SEP
PY 2013
VL 133
IS 9
BP 2141
EP 2142
DI 10.1038/jid.2013.260
PG 2
WC Dermatology
SC Dermatology
GA 202GY
UT WOS:000323203300011
PM 23842116
ER
PT J
AU Jones, RJ
Gu, DM
Bjorklund, CC
Kuiatse, I
Remaley, AT
Bashir, T
Vreys, V
Orlowski, RZ
AF Jones, Richard J.
Gu, Dongmin
Bjorklund, Chad C.
Kuiatse, Isere
Remaley, Alan T.
Bashir, Tarig
Vreys, Veronique
Orlowski, Robert Z.
TI The Novel Anticancer Agent JNJ-26854165 Induces Cell Death through
Inhibition of Cholesterol Transport and Degradation of ABCA1
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID DENSITY-LIPOPROTEIN-RECEPTOR; ACUTE MYELOGENOUS LEUKEMIA;
MULTIPLE-MYELOMA; GENE-EXPRESSION; MESSENGER-RNA; LDL RECEPTOR;
TRAFFICKING; DISEASE; EFFLUX; APOPTOSIS
AB JNJ-26854165 (serdemetan) has previously been reported to inhibit the function of the E3 ligase human double minute 2, and we initially sought to characterize its activity in models of mantle cell lymphoma (MCL) and multiple myeloma (MM). Serdemetan induced a dose-dependent inhibition of proliferation in both wildtype (wt) and mutant (mut) p53 cell lines, with IC50 values from 0.25 to 3 mu M/l, in association with an S phase cell cycle arrest. Caspase-3 activation was primarily seen in wtp53-bearing cells but also occurred in mutp53-bearing cells, albeit to a lesser extent. 293T cells treated with JNJ-26854165 and serdemetan-resistant fibroblasts displayed accumulation of cholesterol within endosomes, a phenotype reminiscent of that seen in the ATP-binding cassette subfamily A member-1 (ABCA1) cholesterol transport disorder, Tangiers disease. MM and MCL cells had decreased cholesterol efflux and electron microscopy demonstrated the accumulation of lipid whorls, confirming the lysosomal storage disease phenotype. JNJ-26854165 induced induction of cholesterol regulatory genes, sterol regulatory element-binding transcription factor-1 and -2, liver X receptors alpha and beta, along with increased expression of Niemann-Pick disease type-C1 and -C2. However, JNJ-26854165 induced enhanced ABCA1 turnover despite enhancing transcription. Finally, ABCA1 depletion resulted in enhanced sensitivity to JNJ-26854165. Overall, these findings support the hypothesis that serdemetan functions in part by inhibiting cholesterol transport and that this pathway is a potential new target for the treatment of MCL and MM.
C1 [Jones, Richard J.; Gu, Dongmin; Bjorklund, Chad C.; Kuiatse, Isere; Orlowski, Robert Z.] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Houston, TX 77054 USA.
[Orlowski, Robert Z.] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77054 USA.
[Remaley, Alan T.] NHLBI, Lipoprotein Metab Sect, Cardiopulm Branch, NIH, Bethesda, MD 20892 USA.
[Bashir, Tarig; Vreys, Veronique] Janssen Res & Dev, Beerse, Belgium.
RP Jones, RJ (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, 7455 Fannin St,Unit 403, Houston, TX 77054 USA.
EM rjones@mdanderson.org
FU Cancer Center Support Grant [CA16672]
FX Flow cytometry services were provided by the MD Anderson Flow Cytometry
Core Facility, and electron microscopy was performed at the MD Anderson
Electron Microscopy Core Facility with the assistance of Kenneth Dunner,
which are supported by the Cancer Center Support Grant (CA16672). The
authors are grateful to Shubin Xiong for the gift of the p53-/- and dual
p53-/- and HDM-2-/- MEF cells (Houston, Texas) and to Masanori Daibata
for SP-53 cells (Kochi University, Kochi, Japan).
NR 51
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U1 0
U2 13
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD SEP
PY 2013
VL 346
IS 3
BP 381
EP 392
DI 10.1124/jpet.113.204958
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 201RE
UT WOS:000323159900005
PM 23820125
ER
PT J
AU Gasior, M
Tang, R
Rogawski, MA
AF Gasior, Maciej
Tang, Rebecca
Rogawski, Michael A.
TI Long-Lasting Attenuation of Amygdala-Kindled Seizures after
Convection-Enhanced Delivery of Botulinum Neurotoxins A and B into the
Amygdala in Rats
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; TOXIN-A; TETANUS TOXIN; DOUBLE-BLIND;
SPINAL-CORD; EPILEPSY; INJECTION; RELEASE; BRAIN; TRANSMITTERS
AB Botulinum neurotoxins (BoNTs) are well recognized to cause potent, selective, and long-lasting neuroparalytic actions by blocking cholinergic neurotransmission to muscles and glands. There is evidence that BoNT isoforms can also inhibit neurotransmission in the brain. In this study, we examined whether locally delivered BoNT/A and BoNT/B can attenuate kindling measures in amygdala-kindled rats. Male rats were implanted with a combination infusion cannula-stimulating electrode assembly into the right basolateral amygdala. Fully kindled animals received a single infusion of vehicle or BoNT/A or BoNT/B at doses of 1, 3.2, or 10 ng over a 20-minute period by convection-enhanced delivery. Electrographic (EEG) and behavioral kindling measures were determined at selected times during the 3- to 64-day period after the infusion. BoNT/B produced a dose-dependent elevation in after-discharge threshold and duration and a reduction in the seizure stage and duration of behavioral seizures that lasted for up to 50 days after infusion. BoNT/A had similar effects on EEG measures; behavioral seizure measures were also reduced, but the effect did not reach statistical significance. The effects of both toxins on EEG and behavioral measures progressively resolved during the latter half of the observation period. Animals gained weight normally, maintained normal body temperature, and did not show altered behavior. This study demonstrates for the first time that locally delivered BoNTs can produce prolonged inhibition of brain excitability, indicating that they could be useful for the treatment of brain disorders, including epilepsy, that would benefit from long-lasting suppression of neurotransmission within a circumscribed brain region.
C1 [Gasior, Maciej; Tang, Rebecca; Rogawski, Michael A.] NINDS, Epilepsy Res Sect, NIH, Bethesda, MD 20892 USA.
[Rogawski, Michael A.] Univ Calif Davis, Sch Med, Dept Neurol, Sacramento, CA 95817 USA.
RP Rogawski, MA (reprint author), Univ Calif Davis, Sch Med, Dept Neurol, 4860 Y St,Suite 3700, Sacramento, CA 95817 USA.
EM rogawski@ucdavis.edu
RI Rogawski, Michael/B-6353-2009
OI Rogawski, Michael/0000-0002-3296-8193
FU National Institutes of Health National Institute of Neurological
Disorders and Stroke [NS002877, NS072094, NS079202]; Intramural Research
Program of the National Institutes of Health [National Institute of
Neurological Disorders and Stroke]
FX This work was supported by the National Institutes of Health National
Institute of Neurological Disorders and Stroke [Grants NS002877,
NS072094, NS079202]; and the Intramural Research Program of the National
Institutes of Health [National Institute of Neurological Disorders and
Stroke].
NR 40
TC 3
Z9 3
U1 1
U2 2
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD SEP
PY 2013
VL 346
IS 3
BP 528
EP 534
DI 10.1124/jpet.113.205070
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 201RE
UT WOS:000323159900019
PM 23772062
ER
PT J
AU Tooley, PW
Browning, M
Leighty, RM
AF Tooley, Paul W.
Browning, Marsha
Leighty, Robert M.
TI Inoculum Density Relationships for Infection of Some Eastern US Forest
Species by Phytophthora ramorum
SO JOURNAL OF PHYTOPATHOLOGY
LA English
DT Article
DE epidemiology; ramorum blight; sudden oak death
ID PARASITICA VAR-NICOTIANAE; OAK DEATH PATHOGEN; COLLETOTRICHUM-COCCODES;
WETNESS DURATION; PLANT-AGE; SUSCEPTIBILITY; CALIFORNIA; RESISTANCE;
INOCULATION; TEMPERATURE
AB Our objectives were to establish inoculum density relationships between P.ramorum and selected hosts using detached leaf and whole-plant inoculations. Young plants and detached leaves of Quercus prinus (Chestnut oak), Q.rubra (Northern red oak), Acer rubrum (red maple), Kalmia latifolia (mountain laurel) and Rhododendron Cunningham's White' were dip-inoculated with varying numbers of P.ramorum sporangia, and the total number of diseased and healthy leaves recorded following incubation at 20 degrees C and 100% relative humidity. Calibration threshold estimates for obtaining 50% infected leaves based on linear analysis ranged from 36 to 750 sporangia/ml for the five hosts. Half-life (LD50) estimates (the number of spores for which the per cent of diseased leaves reaches 50% of its total) from asymptotic regression analysis ranged from 94 to 319 sporangia/ml. Statistically significant differences (P=0.0076) were observed among hosts in per cent infection in response to increased inoculum density. Inoculum threshold estimates based on studies with detached leaves were comparable to those obtained using whole plants. P.ramorum hosts and will be useful in disease prediction and for development of pest risk assessments.
C1 [Tooley, Paul W.; Browning, Marsha] ARS, Foreign Dis Weed Sci Res Unit, USDA, Ft Detrick, MD 21702 USA.
[Leighty, Robert M.] Frederick Natl Lab Canc Res, Data Management Serv, Frederick, MD 21702 USA.
RP Tooley, PW (reprint author), ARS, Foreign Dis Weed Sci Res Unit, USDA, 1301 Ditto Ave, Ft Detrick, MD 21702 USA.
EM paul.tooley@ars.usda.gov
FU USDA Forest Service; Pacific Southwest Research Station
FX We gratefully acknowledge the funding for this project provided by the
USDA Forest Service, Pacific Southwest Research Station, and the
technical assistance of Kristin Henderson.
NR 44
TC 5
Z9 5
U1 1
U2 29
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0931-1785
J9 J PHYTOPATHOL
JI J. Phytopathol.
PD SEP
PY 2013
VL 161
IS 9
BP 595
EP 603
DI 10.1111/jph.12107
PG 9
WC Plant Sciences
SC Plant Sciences
GA 195NB
UT WOS:000322708500001
ER
PT J
AU Khraiwesh, H
Lopez-Dominguez, JA
Lopez-Lluch, G
Navas, P
de Cabo, R
Ramsey, JJ
Villalba, JM
Gonzalez-Reyes, JA
AF Khraiwesh, Husam
Lopez-Dominguez, Jose A.
Lopez-Lluch, Guillermo
Navas, Placido
de Cabo, Rafael
Ramsey, Jon J.
Villalba, Jose M.
Gonzalez-Reyes, Jose A.
TI Alterations of Ultrastructural and Fission/Fusion Markers in Hepatocyte
Mitochondria From Mice Following Calorie Restriction With Different
Dietary Fats
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Calorie restriction; Dietary fat; Hepatocyte; Mice; Mitochondrial
ultrastructure; Mitochondrial fission and fusion
ID SKELETAL-MUSCLE MITOCHONDRIA; OXYGEN SPECIES PRODUCTION; RAT-LIVER
MITOCHONDRIA; OXIDATIVE DNA-DAMAGE; PROTON LEAK; SHORT-TERM; PEROXIDE
PRODUCTION; FISCHER-344 RATS; ACID-COMPOSITION; RHESUS-MONKEYS
AB We analyzed ultrastructural changes and markers of fission/fusion in hepatocyte mitochondria from mice submitted to 40% calorie restriction (CR) for 6 months versus ad-libitum-fed controls. To study the effects of dietary fat under CR, animals were separated into three CR groups with soybean oil (also in controls), fish oil, and lard. CR induced differential changes in hepatocyte and mitochondrial size, in the volume fraction occupied by mitochondria, and in the number of mitochondria per hepatocyte. The number of cristae per mitochondrion was significantly higher in all CR groups compared with controls. Proteins related to mitochondrial fission (Fis1 and Drp1) increased with CR, but no changes were detected in proteins involved in mitochondrial fusion (Mfn1, Mfn2, and OPA1). Although many of these changes could be attributed to CR regardless of dietary fat, changing membrane lipid composition by different fat sources did modulate the effects of CR on hepatocyte mitochondria.
C1 [Khraiwesh, Husam; Lopez-Dominguez, Jose A.; Villalba, Jose M.; Gonzalez-Reyes, Jose A.] Univ Cordoba, Dept Biol Celular Fisiol & Inmunol, Cordoba 14014, Spain.
[Lopez-Lluch, Guillermo; Navas, Placido] Univ Pablo Olavide, Ctr Andaluz Biol Desarrollo, Inst Salud Carlos III, CSIC,CIBERER, Seville, Spain.
[de Cabo, Rafael] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA.
[Ramsey, Jon J.] Univ Calif Davis, VM Mol Biosci, Davis, CA 95616 USA.
RP Gonzalez-Reyes, JA (reprint author), Univ Cordoba, Dept Biol Celular Fisiol & Inmunol, Campus Rabanales,Edificio Severo Ochoa,3A Planta, Cordoba 14014, Spain.
EM bc1gorej@uco.es
RI Gonzalez-Reyes, Jose A/K-1367-2014; Lopez-Lluch, Guillermo/N-4742-2014;
de Cabo, Rafael/J-5230-2016;
OI Gonzalez-Reyes, Jose A/0000-0003-1918-5490; Lopez-Lluch,
Guillermo/0000-0001-9830-8502; de Cabo, Rafael/0000-0002-3354-2442; ,
rafael/0000-0003-2830-5693
FU NIH [1R01AG028125-01A1]; Ministerio de Economia y Competitividad
[BFU2011-23578]; Junta de Andalucia Proyectos de Excelencia
[P09-CVI-4887]; Junta de Andalucia Proyectos Internacionales; Junta de
Andalucia [BIO-276]; University of Cordoba [BIO-276]; Agencia Espanola
de Cooperacion Internacional al Desarrollo; Spanish Ministerio de
Educacion
FX This work was supported by NIH grant 1R01AG028125-01A1 (to J.J.R., P.N.,
and J.M.V.), Ministerio de Economia y Competitividad BFU2011-23578 (to
J.M.V.), Junta de Andalucia Proyectos de Excelencia grant P09-CVI-4887
(to J.M.V.), Junta de Andalucia Proyectos Internacionales grant (to
J.M.V.), and BIO-276 (Junta de Andalucia and the University of Cordoba,
to J.M.V.). H. K. was funded by a predoctoral fellowship of the Agencia
Espanola de Cooperacion Internacional al Desarrollo and BIO-276.
J.A.L.D. was funded by a predoctoral fellowship of the Spanish
Ministerio de Educacion and BIO-276.
NR 61
TC 14
Z9 14
U1 0
U2 7
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD SEP
PY 2013
VL 68
IS 9
BP 1023
EP 1034
DI 10.1093/gerona/glt006
PG 12
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 198HL
UT WOS:000322913000005
PM 23403066
ER
PT J
AU Gharib, AM
Zahiri, H
Matta, J
Pettigrew, RI
Abd-Elmoniem, KZ
AF Gharib, Ahmed M.
Zahiri, Homeira
Matta, Jatin
Pettigrew, Roderic I.
Abd-Elmoniem, Khaled Z.
TI Feasibility of coronary artery wall thickening assessment in
asymptomatic coronary artery disease using phase-sensitive
dual-inversion recovery MRI at 3 T
SO MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE Atherosclerosis; Coronary artery imaging; Vessel wall; Black blood MRI;
Phase sensitive; Dual-inversion recovery; 3 T
ID MAGNETIC-RESONANCE ANGIOGRAPHY; VESSEL-WALL; NAVIGATOR CORRECTION;
COMPUTED-TOMOGRAPHY; INITIAL-EXPERIENCE; SPATIAL-RESOLUTION; MOTION
CORRECTION; IMAGE QUALITY; ATHEROSCLEROSIS; TESLA
AB Objectives: The purpose of this study was to (a) investigate the image quality of phase-sensitive dual-inversion recovery (PS-DIR) coronary wall imaging in healthy subjects and in subjects with known coronary artery disease (CAD) and to (b) investigate the utilization of PS-DIR at 3 T in the assessment of coronary artery thickening in subjects with asymptomatic but variable degrees of CAD.
Materials and Methods: A total of 37 subjects participated in this institutional review board-approved and HIPAA-compliant study. These included 21 subjects with known CAD as identified on multidetector computed tomography angiography (MDCT). Sixteen healthy subjects without known history of CAD were included. All subjects were scanned using free-breathing PS-DIR magnetic resonance imaging (MRI) for the assessment of coronary wall thickness at 3 T. Lumen-tissue contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR) and quantitative vessel parameters including lumen area and wall thickness were measured. Statistical analyses were performed.
Results: PS-DIR was successfully completed in 76% of patients and in 88% of the healthy subjects. Phase-sensitive signed-magnitude reconstruction, compared to modulus-magnitude images, significantly improved lumen-tissue CNR in healthy subjects (26.73 +/- 11.95 vs. 14.65 +/- 9.57, P < .001) and in patients (21.45 +/- 7.61 vs. 16.65 +/- 5.85, P < .001). There was no difference in image CNR and SNR between groups. In arterial segments free of plaques, coronary wall was thicker in patients in comparison to healthy subjects (1.74 +/- 0.27 mm vs. 1.17 +/- 0.14 mm, P < .001), without a change in lumen area (4.51 +/- 2.42 mm(2) vs. 5.71 +/- 3.11 mm(2), P = .25).
Conclusions: This is the first study to demonstrate the feasibility of successfully obtaining vessel wall images at 3 T using PS-DIR in asymptomatic patients with known variable degrees of CAD as detected by MDCT. This was achieved with a fixed subject-invariant planning of blood signal nulling. With that limitation alleviated, PS-DIR coronary wall MRI is capable of detecting arterial thickening and positive arterial remodeling at 3 T in asymptomatic CAD. Published by Elsevier Inc.
C1 [Gharib, Ahmed M.; Matta, Jatin; Abd-Elmoniem, Khaled Z.] Natl Inst Diabet & Digest & Kidney Dis, Biomed & Metab Imaging Branch, NIH, Bethesda, MD USA.
[Zahiri, Homeira] NIH, Clin Res Ctr, Bethesda, MD 20892 USA.
[Pettigrew, Roderic I.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA.
RP Abd-Elmoniem, KZ (reprint author), NIH, Clin Res Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM abdelmoniemkz@mail.nih.gov
RI Gharib, Ahmed/O-2629-2016; Abd-Elmoniem, Khaled/B-9289-2008
OI Gharib, Ahmed/0000-0002-2476-481X; Abd-Elmoniem,
Khaled/0000-0002-1001-1702
FU Intramural NIH HHS [Z99 DK999999]
NR 49
TC 5
Z9 5
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0730-725X
J9 MAGN RESON IMAGING
JI Magn. Reson. Imaging
PD SEP
PY 2013
VL 31
IS 7
BP 1051
EP 1058
DI 10.1016/j.mri.2013.03.011
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 198TG
UT WOS:000322944600003
PM 23642801
ER
PT J
AU Dabire, KR
Sawadodgo, S
Diabate, A
Toe, KH
Kengne, P
Ouari, A
Costantini, C
Gouagna, C
Simard, F
Baldet, T
Lehmann, T
Gibson, G
AF Dabire, K. R.
Sawadodgo, S.
Diabate, A.
Toe, K. H.
Kengne, P.
Ouari, A.
Costantini, C.
Gouagna, C.
Simard, F.
Baldet, T.
Lehmann, T.
Gibson, G.
TI Assortative mating in mixed swarms of the mosquito Anopheles gambiae
s.s. M and S molecular forms, in Burkina Faso, West Africa
SO MEDICAL AND VETERINARY ENTOMOLOGY
LA English
DT Article
DE Anopheles gambiae s.s.; assortative mating; mate recognition; mating
behaviour; mixed swarm; molecular forms; Burkina Faso
ID INSECTICIDE RESISTANCE; MALARIA TRANSMISSION; TRANSGENIC MOSQUITOS;
INCIPIENT SPECIATION; TRANSFERRED SPERM; DNA ANALYSIS; CULICIDAE;
DIPTERA; BEHAVIOR; COMPLEX
AB The molecular form composition of Anopheles gambiae Giles s.s. (Diptera: Culicidae) mating swarms and the associated mating pairs (copulae) were investigated during two rainy seasons (July to October, 2005 and July to November, 2006) in the villages of Soumousso and Vallee du Kou (VK7). Although the habitats of these villages differ markedly, sympatric populations of M and S molecular forms of An. gambiae s.s. occur in both places periodically. The main aim was to assess the degree to which these molecular forms mate assortatively. In Soumousso, a wooded savannah habitat, the majority of swarm samples consisted of only S-form males (21/28), although a few M-form males were found in mixed M- and S-form swarms. In VK7, a rice growing area, the majority of swarm samples consisted of only M-form males (38/62), until October and November 2006, when there were nearly as many mixed-form as single-form swarms. Overall, approximate to 60% of M- and S-form swarms were temporally or spatially segregated; the two forms were effectively prevented from encountering each other. Of the remaining 40% of swarms, however, only about half were single-form and the rest were mixed-form. Of the 33 copulae collected from mixed-form swarms, only four were mixed-form pairs, significantly fewer than expected by random pairing between forms ((2) = 10.34, d.f. = 2, P < 0.01). Finally, all specimens of inseminated females were of the same form as the sperm contained within their spermatheca (n = 91), even for the four mixed-form copulae. These findings indicate that assortative mating occurs within mixed-form swarms, mediated most probably by close-range mate recognition cues.
C1 [Dabire, K. R.; Sawadodgo, S.; Diabate, A.; Toe, K. H.; Ouari, A.] IRSS, Bobo Dioulasso, West Africa, Burkina Faso.
[Kengne, P.; Costantini, C.; Gouagna, C.; Simard, F.] Univ Montpellier 2, Univ Montpellier 1, IRD, MIVEGEC, Montpellier, France.
[Baldet, T.] Ctr Rech Entomol Cotonou, Ctr Cooperat Int Rech Agron Dev, IRD, Cotonou, Benin.
[Lehmann, T.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
[Gibson, G.] Univ Greenwich Medway, Nat Resources Inst, Dept Agr Hlth & Environm, Chatham, Kent, England.
RP Dabire, KR (reprint author), IRSS Ctr Muraz, BP 390, Bobo Dioulasso, West Africa, Burkina Faso.
EM dabire_roch@hotmail.com
RI SIMARD, Frederic/J-9489-2016
OI SIMARD, Frederic/0000-0002-2871-5329
FU Multilateral Initiative on Malaria (MIM) Project through
UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training
in Tropical Diseases (TDR) [A60098]; TDR Programme [A50299]
FX This study was financially supported by the Multilateral Initiative on
Malaria (MIM) Project A60098 through the UNICEF/UNDP/World Bank/WHO
Special Programme for Research and Training in Tropical Diseases (TDR)
and by a grant from the TDR Programme to G.G. (A50299). The authors are
grateful to the populations of Soumousso and Vallee du Kou who made this
study possible. We thank Stephen Young (NRI) for assistance with
statistical analyses and Jeremi Rouamba (IRSS) for the maps of VK7 and
Soumousso.
NR 45
TC 20
Z9 20
U1 1
U2 22
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-283X
J9 MED VET ENTOMOL
JI Med. Vet. Entomol.
PD SEP
PY 2013
VL 27
IS 3
BP 298
EP 312
DI 10.1111/j.1365-2915.2012.01049.x
PG 15
WC Entomology; Veterinary Sciences
SC Entomology; Veterinary Sciences
GA 199KC
UT WOS:000322992400007
PM 23360106
ER
PT J
AU Xu, LY
Panel, V
Ma, XR
Du, C
Hugendubler, L
Gavrilova, O
Liu, A
McLaughlin, T
Kaestner, KH
Muellera, E
AF Xu, Lingyan
Panel, Valentine
Ma, Xinran
Du, Chen
Hugendubler, Lynne
Gavrilova, Oksana
Liu, Alice
McLaughlin, Tracey
Kaestner, Klaus H.
Muellera, Elisabetta
TI The Winged Helix Transcription Factor Foxa3 Regulates Adipocyte
Differentiation and Depot-Selective Fat Tissue Expansion
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID NUCLEAR FACTOR 3-GAMMA; ADIPOSE-TISSUE; HEPATOCYTE; METABOLISM; GENES
AB Conversion of mesenchymal stem cells into terminally differentiated adipocytes progresses sequentially through regulated transcriptional steps. While it is clear that the late phases of adipocyte maturation are governed by the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR gamma), less is known about the transcriptional control of the initial stages of differentiation. To identify early regulators, we performed a small interfering RNA (siRNA) screen of Forkhead-box genes in adipocytes and show here for the first time that the winged helix factor Foxa3 promotes adipocyte differentiation by cooperating with C/EBP beta and -delta to transcriptionally induce PPAR gamma expression. Furthermore, we demonstrate that mice with genetic ablation of Foxa3 have a selective decrease in epididymal fat depot and a cell-autonomous defect to induce PPAR gamma specifically in their visceral adipocytes. In obese subjects, FOXA3 is differentially expressed in visceral and subcutaneous adipose depots. Overall, our study implicates Foxa3 in the regulation of adipocyte differentiation and depot-selective adipose tissue expansion.
C1 [Xu, Lingyan; Panel, Valentine; Ma, Xinran; Du, Chen; Hugendubler, Lynne; Muellera, Elisabetta] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD USA.
[Gavrilova, Oksana] NIDDK, Mouse Metab Core Lab, NIH, Bethesda, MD USA.
[Liu, Alice; McLaughlin, Tracey] Stanford Univ, Med Ctr, Dept Med, Div Endocrinol, Stanford, CA 94305 USA.
[Kaestner, Klaus H.] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
[Kaestner, Klaus H.] Univ Penn, Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA.
RP Muellera, E (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD USA.
EM elisabettam@niddk.nih.gov
FU Intramural Research Program of the National Institutes of Health;
National Institute of Diabetes and Digestive and Kidney Diseases;
[P01-DK049210]
FX This research was supported by P01-DK049210 (to K.H.K.) and by the
Intramural Research Program of the National Institutes of Health and
National Institute of Diabetes and Digestive and Kidney Diseases (to
E.M.).
NR 18
TC 10
Z9 10
U1 1
U2 7
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 SEP
PY 2013
VL 33
IS 17
BP 3392
EP 3399
DI 10.1128/MCB.00244-13
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 196ZY
UT WOS:000322817600001
PM 23798556
ER
PT J
AU Wang, TTY
Schoene, NW
Kim, EK
Kim, YS
AF Wang, Thomas T. Y.
Schoene, Norberta W.
Kim, Eun-Kyung
Kim, Young S.
TI Pleiotropic effects of the sirtuin inhibitor sirtinol involves
concentration-dependent modulation of multiple nuclear receptor-mediated
pathways in androgen-responsive prostate cancer cell LNCaP
SO MOLECULAR CARCINOGENESIS
LA English
DT Article
DE androgen; estrogen; insulin-like growth factor-1; xenobiotic metabolism;
sirtinol; sirtuin
ID SACCHAROMYCES-CEREVISIAE; CYCLE ARREST; SIR2; P21(WAF1/CIP1);
IDENTIFICATION; DEACETYLASES; RESVERATROL; PROGRESSION; ACTIVATION;
SENESCENCE
AB Sirtinol is a purported specific inhibitor of the nicotinamide adenine dinucleotide (NAD)-dependent type III histone deacetylase (also known as sirtuin). Sirtinol has been used extensively to identify chemopreventive/chemotherapeutic agents that modulate the sirtuins. However, the molecular effect of sirtinol other than serving as sirtuin inhibitor in cells is less clear. The present study addressed this deficiency in the literature. Based on structural similarity with plant-derived cancer preventive/therapeutic compounds such as 3', 3'-diindolylmethane, resveratrol, and genistein, we hypothesized that sirtinol may act on pathways similar to that affected by these compounds in the human prostate cancer cell LNCaP. We found that treatment of LNCaP cells with sirtinol led to concentration-dependent effects on multiple pathways. Sirtinol inhibited LNCaP cell cycle and growth that was correlated with up-regulation of cyclin-dependent kinase inhibitor 1A mRNA and protein levels. This effect of sirtinol may due in part to modulation of androgen, estrogen, and insulin-like growth factor-1 mediated pathways as sirtinol treatment led to inhibition of mRNA and protein expression of marker genes involved in these pathways. We also found sirtinol activates aryl hydrocarbon-dependent pathways in LNCaP cells. The effects of sirtinol were observed at 25 mu M, a concentration lower than Ki (38 mu M) for sirtuin activity. Based on these results we reasoned that sirtinol exerts pleiotropic effects in cells and that biological effects of sirtinol may not be due solely to inhibition of sirtuin. (c) 2012 Wiley Periodicals, Inc.
C1 [Wang, Thomas T. Y.; Schoene, Norberta W.] ARS, Diet Genom & Immunol Lab, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD 20705 USA.
[Kim, Eun-Kyung; Kim, Young S.] NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
RP Wang, TTY (reprint author), ARS, Genom & Immunol Lab, Beltsville Human Nutr Res Ctr, USDA, 10300 Baltimore Ave,Bldg 307C,Room 132, Beltsville, MD 20705 USA.
FU National Cancer Institute; [1235-51530-053-00D]
FX We would like to thank Drs. Allison Yates and Joseph Urban for reviewing
this manuscript. This work was supported by US appropriated funds to
USDA project number 1235-51530-053-00D (TTYW, NWS) and the National
Cancer Institute (E-KK, YSK).
NR 30
TC 8
Z9 9
U1 3
U2 17
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0899-1987
J9 MOL CARCINOGEN
JI Mol. Carcinog.
PD SEP
PY 2013
VL 52
IS 9
BP 676
EP 685
DI 10.1002/mc.21906
PG 10
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA 198FZ
UT WOS:000322908900002
PM 22495798
ER
PT J
AU Zhang, Q
Pan, J
Wang, Y
Lubet, R
You, M
AF Zhang, Qi
Pan, Jing
Wang, Yian
Lubet, Ronald
You, Ming
TI Beetroot red (betanin) inhibits vinyl carbamate- and
benzo(a)pyrene-induced lung tumorigenesis through apoptosis
SO MOLECULAR CARCINOGENESIS
LA English
DT Article
DE betanin; vinyl carbamate; benzo(a)pyrene; CD31; caspase-3; PARP
ID A/J MICE; CANCER CHEMOPREVENTION; EXTRACT; CARCINOGENESIS; TUMORS;
ANTIOXIDANTS; PROGRESSION; ADRIAMYCIN; CASPASES; EFFICACY
AB Betanin, also called beetroot red, has been extensively used as a food colorant. In this study, the chemopreventive activity of betanin by oral consumption was investigated in two mouse lung tumor models. Vinyl carbamate (VC) and benzo(a)pyrene (B(a)P) were used to induce lung tumors, and female A/J mice were treated with betanin in drinking water. Betanin significantly decreased tumor multiplicity and tumor load induced by both carcinogens. Tumor multiplicity and tumor load were decreased by 20% and 39% in the VC lung model, and by 46% and 65% in the B(a)P lung model, respectively. Betanin reduced the number of CD31+ endothelial microvessels and increased the expression of caspase-3, suggesting that the lung tumor inhibitory effects were through induction of apoptosis and inhibition of angiogenesis. Betanin also induced apoptosis through activated caspase-3, -7, -9, and PARP in human lung cancer cell lines. Our data show that betanin significantly inhibits lung tumorigenesis in A/J mice and merits investigation as a chemopreventive agent for human lung cancer. (c) 2012 Wiley Periodicals, Inc.
C1 [Zhang, Qi; Pan, Jing; Wang, Yian; You, Ming] Washington Univ, Dept Surg, Sch Med, St Louis, MO 63110 USA.
[Lubet, Ronald] NCI, Chemoprevent Branch, Bethesda, MD 20892 USA.
RP You, M (reprint author), Washington Univ, Dept Surg, Campus Box 8109,660 South Euclid Ave, St Louis, MO 63110 USA.
NR 23
TC 6
Z9 8
U1 0
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0899-1987
J9 MOL CARCINOGEN
JI Mol. Carcinog.
PD SEP
PY 2013
VL 52
IS 9
BP 686
EP 691
DI 10.1002/mc.21907
PG 6
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA 198FZ
UT WOS:000322908900003
PM 22456940
ER
PT J
AU Hall, JM
Korach, KS
AF Hall, Julie M.
Korach, Kenneth S.
TI Endocrine disrupting chemicals promote the growth of ovarian cancer
cells via the ER-CXCL12-CXCR4 signaling axis
SO MOLECULAR CARCINOGENESIS
LA English
DT Article
DE endocrine disrupting chemicals (EDCs); ovarian cancer; estrogen
receptor; cell proliferation; CXCL12; CXCR4
ID ESTROGEN-RECEPTOR-ALPHA; GENOME-WIDE ANALYSIS; BREAST-CANCER;
GENE-EXPRESSION; CHEMOKINE CXCL12; BISPHENOL-A; ACTIVATION; MECHANISMS;
GENISTEIN; CARCINOMA
AB The majority of ovarian cancers over-express the estrogen receptor (ER) and grow in response to estrogens. We previously demonstrated that ER induction of the chemokine CXCL12 (stromal cell-derived factor-1) is required for estradiol (E2)-stimulated proliferation of human ovarian carcinoma cells. In the current study, we report that known endocrine disrupting chemicals (EDCs) display mitogenic activities in ovarian cancer cells via their ability to activate the ER and upregulate CXCL12 expression. Notably, the EDCs genistein, bisphenol A and HPTE stimulated both cell proliferation and induction of CXCL12 mRNA and protein in a manner comparable to estradiol. The effects were completely attenuated by the ER antagonist ICI 182,780, revealing that observed activities of these agents were receptor-mediated. In cell proliferation assays, the mitogenic effects of estradiol and EDCs were obviated by siRNAs targeting CXCL12 and restored upon addition of exogenous CXCL12. Furthermore, an inhibitor to the CXCL12 receptor CXCR4 completely attenuated growth-stimulatory effects of E2 and EDCs. These studies highlight a potential role of EDCs possessing estrogenic activities in the etiology of ovarian cancer. Moreover, they suggest that the ER-CXCL12-CXCR4 signaling axis may represent a promising target for development of therapeutics for ER+ ovarian cancers. (c) 2012 Wiley Periodicals, Inc.
C1 [Hall, Julie M.] Campbell Univ, Coll Pharm & Hlth Sci, Buies Creek, NC 27506 USA.
[Korach, Kenneth S.] NIEHS, Lab Reprod & Dev Toxicol, Receptor Biol Sect, NIH, Res Triangle Pk, NC 27709 USA.
RP Hall, JM (reprint author), Campbell Univ, Coll Pharm & Hlth Sci, POB 1090, Buies Creek, NC 27506 USA.
OI Korach, Kenneth/0000-0002-7765-418X
FU Division of Intramural Research, National Institutes of Environmental
Health Sciences, National Institutes of Health [Z01ES70065]
FX This work was supported by the Division of Intramural Research, National
Institutes of Environmental Health Sciences, National Institutes of
Health to KSK (Z01ES70065).
NR 49
TC 16
Z9 16
U1 1
U2 19
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0899-1987
J9 MOL CARCINOGEN
JI Mol. Carcinog.
PD SEP
PY 2013
VL 52
IS 9
BP 715
EP 725
DI 10.1002/mc.21913
PG 11
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA 198FZ
UT WOS:000322908900006
PM 22549810
ER
PT J
AU Fukuda, Y
Takenaka, K
Sparreboom, A
Cheepala, SB
Wu, CP
Ekins, S
Ambudkar, SV
Schuetz, JD
AF Fukuda, Yu
Takenaka, Kazumasa
Sparreboom, Alex
Cheepala, Satish B.
Wu, Chung-Pu
Ekins, Sean
Ambudkar, Suresh V.
Schuetz, John D.
TI Human Immunodeficiency Virus Protease Inhibitors Interact with ATP
Binding Cassette Transporter 4/Multidrug Resistance Protein 4: A Basis
for Unanticipated Enhanced Cytotoxicity
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID MRP4 CONFERS RESISTANCE; HIV-INFECTED PATIENTS; MULTIDRUG-RESISTANCE;
BREAST-CANCER; IN-VITRO; EFFLUX TRANSPORTER; ABC TRANSPORTERS; ANTIVIRAL
DRUGS; P-GLYCOPROTEIN; CELL-LINES
AB Human immunodeficiency virus (HIV) pharmacotherapy, by combining different drug classes such as nucleoside analogs and HIV protease inhibitors (PIs), has increased HIV-patient life expectancy. Consequently, among these patients, an increase in non-HIV-associated cancers has produced a patient cohort requiring both HIV and cancer chemotherapy. We hypothesized that multidrug resistance protein 4/ATP binding cassette transporter 4 (MRP4/ABCC4), a widely expressed transporter of nucleoside-based antiviral medications as well as cancer therapeutics might interact with PIs. Among the PIs evaluated (nelfinavir, ritonavir, amprenavir, saquinavir, and indinavir), only nelfinavir both effectively stimulated MRP4 ATPase activity and inhibited substrate-stimulated ATPase activity. Saos2 and human embryonic kidney 293 cells engineered to overexpress MRP4 were then used to assess transport and cytotoxicity. MRP4 expression reduced intracellular accumulation of nelfinavir and consequently conferred survival advantage to nelfinavir cytotoxicity. Nelfinavir blocked Mrp4-mediated export, which is consistent with its ability to increase the sensitivity of MRP4-expressing cells to methotrexate. In contrast, targeted inactivation of Abcc4/Mrp4 in mouse cells specifically enhanced nelfinavir and 9-(2-phosphonylmethoxyethyl) adenine cytotoxicity. These results suggest that nelfinavir is both an inhibitor and substrate of MRP4. Because nelfinavir is a new MRP4/ABCC4 substrate, we developed a MRP4/ABCC4 pharmacophore model, which showed that the nelfinavir binding site is shared with chemotherapeutic substrates such as adefovir and methotrexate. Our studies reveal, for the first time, that nelfinavir, a potent and cytotoxic PI, is both a substrate and inhibitor of MRP4. These findings suggest that HIV-infected cancer patients receiving nelfinavir might experience both enhanced antitumor efficacy and unexpected adverse toxicity given the role of MRP4/ABCC4 in exporting nucleoside-based antiretroviral medications and cancer chemotherapeutics.
C1 [Fukuda, Yu; Takenaka, Kazumasa; Sparreboom, Alex; Cheepala, Satish B.; Schuetz, John D.] St Jude Childrens Res Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA.
[Wu, Chung-Pu; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Ekins, Sean] Collaborat Chem, Fuquay Varina, NC USA.
RP Schuetz, JD (reprint author), St Jude Childrens Res Hosp, Dept Pharmaceut Sci, 262 Danny Thomas Pl,MS 313, Memphis, TN 38105 USA.
EM John.Schuetz@stjude.org
FU ALSAC; National Institutes of Health National Institute of General
Medical Science [2R01-GM60904]; National Institutes of Health National
Cancer Institute [P30-CA21745, P30-CA21865, P30-CA021765]; Intramural
Research Program of the National Institutes of Health [National Cancer
Institute Center for Cancer Research]
FX This work was supported by ALSAC; the National Institutes of Health
National Institute of General Medical Science [Grant 2R01-GM60904]; and
the National Institutes of Health National Cancer Institute [Grants
P30-CA21745, P30-CA21865, and P30-CA021765]. C.-P. W. and S. V. A. were
supported by the Intramural Research Program of the National Institutes
of Health [National Cancer Institute Center for Cancer Research]. S. E.
is an employee of Collaborations in Chemistry and consults for
Collaborative Drug Discovery Inc., as well as companies in the
pharmaceutical industry, and has no conflicts of interest with this
work.
NR 50
TC 16
Z9 16
U1 1
U2 13
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD SEP
PY 2013
VL 84
IS 3
BP 361
EP 371
DI 10.1124/mol.113.086967
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 200BQ
UT WOS:000323041900007
PM 23775562
ER
PT J
AU Arroyo, ECJ
Arroyo, J
AF Cabib, Enrico
Arroyo, Javier
TI How carbohydrates sculpt cells: chemical control of morphogenesis in the
yeast cell wall
SO NATURE REVIEWS MICROBIOLOGY
LA English
DT Article
ID MOTHER-BUD NECK; SACCHAROMYCES-CEREVISIAE; BUDDING YEAST;
GROWTH-CONTROL; CHITIN; PROTEINS; CYTOKINESIS; RING; BIOSYNTHESIS;
ARCHITECTURE
AB In budding yeast, the neck that connects the mother and daughter cell is the site of essential functions such as organelle trafficking, septum formation and cytokinesis. Therefore, the morphology of this region, which depends on the surrounding cell wall, must be maintained throughout the cell cycle. Growth at the neck is prevented, redundantly, by a septin ring inside the cell membrane and a chitin ring in the cell wall. Here, we describe recent work supporting the hypothesis that attachment of the chitin ring, which forms at the mother-bud neck during budding, to beta-1,3-glucan in the cell wall is necessary to stop growth at the neck. Thus, in this scenario, chemistry controls morphogenesis.
C1 [Cabib, Enrico] NIDDK, Lab Biochem & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Arroyo, Javier] Univ Complutense Madrid, Fac Farm, Dept Microbiol 2, E-28040 Madrid, Spain.
[Arroyo, Javier] Inst Ramon y Cajal Invest Sanitarias, Madrid 28040, Spain.
RP Arroyo, ECJ (reprint author), NIDDK, Lab Biochem & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
EM enricoc@bdg10.niddk.nih.gov
RI Arroyo, Javier/E-9308-2016
OI Arroyo, Javier/0000-0002-1971-1721
FU US National Institutes of Health grant (as part of the Intramural
Research Program of the National Institutes of Diabetes and Digestive
and Kidney Diseases); Spanish Government Ministry of Economy and
Competitiveness [BIO2010-22146]; Universidad Complutense de Madrid
[GR58/08]; Comunidad de Madrid [S2010/BDM-2414]; European Science
Foundation [06-RNP-132]
FX The authors thank V. Cid, O. Cohen-Fix, P. Perez, M. Reidy and C.
Vazquez de Aldana for critical reading of the manuscript, and R. Garcia
for help with the figures. E. C. was supported by a US National
Institutes of Health grant (as part of the Intramural Research Program
of the National Institutes of Diabetes and Digestive and Kidney
Diseases). J.A. acknowledges all the members of his laboratory for their
dedicated work, and C. Nombela and the Special Chair in Genomics and
Proteomics for their support. Research in the J.A. laboratory is
supported by the Spanish Government Ministry of Economy and
Competitiveness (grant BIO2010-22146), the Universidad Complutense de
Madrid (grant GR58/08), the Comunidad de Madrid (grant S2010/BDM-2414)
and the European Science Foundation (grant 06-RNP-132).
NR 66
TC 0
Z9 0
U1 5
U2 18
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1740-1526
EI 1740-1534
J9 NAT REV MICROBIOL
JI Nat. Rev. Microbiol.
PD SEP
PY 2013
VL 11
IS 9
BP 648
EP 655
DI 10.1038/nrmicro3090
PG 8
WC Microbiology
SC Microbiology
GA 202HU
UT WOS:000323205500013
ER
PT J
AU Ananth, CV
Wilcox, AJ
Gyamfi-Bannerman, C
AF Ananth, Cande V.
Wilcox, Allen J.
Gyamfi-Bannerman, Cynthia
TI Obstetrical Interventions for Term First Deliveries in the US
SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY
LA English
DT Article
DE obstetrical interventions; elective deliveries; caesarean delivery;
labour induction
ID UNITED-STATES; NEONATAL-MORTALITY; CESAREAN DELIVERY; VAGINAL BIRTHS;
PRETERM BIRTH; OUTCOMES; RATES; RISK; SECTION; INFANT
AB Background: Labour induction and caesarean are increasingly done without clinical indication. However, little is known about the prevalence of such interventions, or the characteristics of women who receive them. We used the 2003 revision of the US birth certificates to summarise recorded interventions and to characterise maternal profiles associated with such interventions.
Methods: We carried out a retrospective study of 2.35 million primiparous women delivering singleton live births at 37-44 weeks in the US from 2005 to 2008. We used the 2003 revision of the birth certificate to define delivery categories: 'indicated' were those with induced labour or pre-labour caesarean for hypertension, diabetes, chorioamnionitis, failed cephalic version at >= 40 weeks, growth restriction (<3rd centile), or post-term (>= 42 weeks); those with pre-labour caesarean with breech at >= 39 weeks; or those with caesarean with labour lasting >= 12h, failed trial of labour, vacuum/forceps extraction, or fetal intolerance to labour. Remaining deliveries with induction/caesarean were classified as non-indicated' and all other deliveries 'spontaneous'.
Results: Half of all term first births (50%) were delivered after intervention, and half of interventions were non-indicated (26% of all deliveries). Women with interventions were more likely to deliver on a weekday. Non-indicated interventions were more common among socially advantaged women.
Conclusions: Nearly a quarter of US term first deliveries had an indicated intervention, and another quarter received intervention without a recorded clinical indication. Both numbers are probably underestimates.
C1 [Ananth, Cande V.; Gyamfi-Bannerman, Cynthia] Columbia Univ, Dept Obstet & Gynecol, Med Ctr, New York, NY 10032 USA.
[Ananth, Cande V.] Columbia Univ, Dept Epidemiol, Joseph L Mailman Sch Publ Hlth, New York, NY 10032 USA.
[Wilcox, Allen J.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
RP Ananth, CV (reprint author), Columbia Univ, Coll Phys & Surg, Dept Obstet & Gynecol, Med Ctr, 622 W 168th St, New York, NY 10032 USA.
EM cande.ananth@columbia.edu
OI Wilcox, Allen/0000-0002-3376-1311
FU NIH, National Institute of Environmental Health Sciences
FX Allen Wilcox's work is supported by the Intramural Research Program of
the NIH, National Institute of Environmental Health Sciences.
NR 23
TC 7
Z9 7
U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-5022
J9 PAEDIATR PERINAT EP
JI Paediatr. Perinat. Epidemiol.
PD SEP
PY 2013
VL 27
IS 5
BP 442
EP 451
DI 10.1111/ppe.12068
PG 10
WC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
SC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
GA 198IA
UT WOS:000322914700003
PM 23930780
ER
PT J
AU Schisterman, EF
Cole, SR
Ye, AJ
Platt, RW
AF Schisterman, Enrique F.
Cole, Stephen R.
Ye, Aijun
Platt, Robert W.
TI Accuracy Loss Due to Selection Bias in Cohort Studies with Left
Truncation
SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY
LA English
DT Article
DE Selection bias; fixed left truncation; variable left truncation
ID SPONTANEOUS-ABORTION; SURVIVAL ANALYSIS; PROBABILITY; MODELS; AGE
AB Background: Selection is a common problem in paediatric and perinatal epidemiology, and truncation can be thought of as missing person time that can result in selection bias. Left truncation, also known as late or staggered entry, may induce selection bias and/or adversely affect precision. There are two kinds of left truncation: fixed left truncation where the start of follow-up is initiated at a set time, and variable left truncation where follow-up begins at a stochastically varying time-point.
Methods: Using data from a time-to-pregnancy study, augmented by a simulation study, we demonstrate the effects of fixed and variable truncation on estimates of the hazard ratio.
Results: First, fixed or variable non-differential left truncation results in a loss of precision. Fixed or variable differential left truncation results in a bias either towards or away from the null as well as a loss of precision. The extent and direction of this bias is a function of the size and direction of the association between exposure and outcome, and occurs in common scenarios and under a wide range of conditions.
Conclusions: As demonstrated in simulation studies, selection bias due to left truncation could have a serious impact on inferences, especially in the case of fixed or variable differential left truncation. When present in epidemiologic studies, proper accounting for left truncation is just as important as proper accounting for right censoring.
C1 [Schisterman, Enrique F.; Ye, Aijun] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Rockville, MD 20854 USA.
[Cole, Stephen R.] UNC Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
[Platt, Robert W.] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada.
[Platt, Robert W.] McGill Univ, Dept Pediat, Montreal, PQ H3A 2T5, Canada.
RP Schisterman, EF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, 6100 Executive Blvd,7B03, Rockville, MD 20854 USA.
EM schistee@mail.nih.gov
OI Platt, Robert/0000-0002-5981-8443; Schisterman,
Enrique/0000-0003-3757-641X
NR 30
TC 17
Z9 17
U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-5022
J9 PAEDIATR PERINAT EP
JI Paediatr. Perinat. Epidemiol.
PD SEP
PY 2013
VL 27
IS 5
BP 491
EP 502
DI 10.1111/ppe.12073
PG 12
WC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
SC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
GA 198IA
UT WOS:000322914700008
PM 23930785
ER
PT J
AU Ahrens, K
Schisterman, E
AF Ahrens, Katherine
Schisterman, Enrique
TI Untitled
SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY
LA English
DT Letter
C1 [Ahrens, Katherine; Schisterman, Enrique] NICHD, Div Epidemiol Stat & Prevent Res, NIH, DHHS, Rockville, MD 20892 USA.
RP Ahrens, K (reprint author), NICHD, Div Epidemiol Stat & Prevent Res, NIH, DHHS, 6100 Bldg,Room 7B05, Rockville, MD 20892 USA.
EM katherine.ahrens@nih.gov
NR 2
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-5022
J9 PAEDIATR PERINAT EP
JI Paediatr. Perinat. Epidemiol.
PD SEP
PY 2013
VL 27
IS 5
BP 503
EP 503
DI 10.1111/ppe.12065
PG 1
WC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
SC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
GA 198IA
UT WOS:000322914700009
PM 23930786
ER
PT J
AU Schug, TT
Heindel, JJ
Camacho, L
Delclos, KB
Howard, P
Johnson, AF
Aungst, J
Keefe, D
Newbold, R
Walker, NJ
Zoeller, RT
Bucher, JR
AF Schug, Thaddeus T.
Heindel, Jerrold J.
Camacho, Luisa
Delclos, K. Barry
Howard, Paul
Johnson, Anne F.
Aungst, Jason
Keefe, Dennis
Newbold, Retha
Walker, Nigel J.
Zoeller, R. Thomas
Bucher, John R.
TI A new approach to synergize academic and guideline-compliant research:
The CLARITY-BPA research program
SO REPRODUCTIVE TOXICOLOGY
LA English
DT Review
DE Bisphenol A; NIEHS; FDA; NTP; Consortium-based research; Low dose
ID BISPHENOL-A
AB Recently, medical research has seen a strong push toward translational research, or "bench to bedside" collaborations, that strive to enhance the utility of laboratory science for improving medical treatment. The success of that paradigm supports the potential application of the process to other fields, such as risk assessment. Close collaboration among academic, government, and industry scientists may enhance the translation of scientific findings to regulatory decision making. The National Toxicology Program (NTP), National Institute of Environmental Health Sciences (NIEHS), and U.S. Food and Drug Administration (FDA) developed a consortium-based research program to link more effectively academic and guideline-compliant research. An initial proof-of-concept collaboration, the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA), uses bisphenol A (BPA) as a test chemical. The CLARITY-BPA program combines a core perinatal guideline-compliant 2-year chronic toxicity study with mechanistic studies/endpoints conducted by academic investigators. Twelve extramural grantees were selected by NIEHS through an RFA-based initiative to participate in the overall study design and conduct disease-relevant investigations using tissues and animals from the core study. While the study is expected to contribute to our understanding of potential effects of BPA, it also has ramifications beyond this specific focus. Through CLARITY-BPA, NIEHS has established an unprecedented level of collaboration among extramural grantees and regulatory researchers. By drawing upon the strengths of academic and regulatory expertise and research approaches, CLARITY-BPA represents a potential new model for filling knowledge gaps, enhancing quality control, informing chemical risk assessment, and identifying new methods or endpoints for regulatory hazard assessments. Published by Elsevier Inc.
C1 [Schug, Thaddeus T.; Heindel, Jerrold J.] NIEHS, NIH, Div Extramural Res, Res Triangle Pk, NC 27709 USA.
[Camacho, Luisa; Delclos, K. Barry] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Howard, Paul] US FDA, Off Sci Coordinat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Johnson, Anne F.] MDB Inc, Durham, NC 27713 USA.
[Aungst, Jason; Keefe, Dennis] US FDA, Off Food Addit Safety, College Pk, MD 20740 USA.
[Newbold, Retha; Walker, Nigel J.; Bucher, John R.] NIEHS, NIH, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Zoeller, R. Thomas] Univ Massachusetts, Dept Biol, Amherst, MA 01003 USA.
RP Schug, TT (reprint author), Div Extramural Res, 530 Davis Dr,Room 3041 Mail Drop K3-15, Morrisville, NC 27560 USA.
EM Schugt@niehs.nih.gov
RI Walker, Nigel/D-6583-2012
OI Walker, Nigel/0000-0002-9111-6855
FU NIEHS [HHSN273201100086U]
FX This article is the work product of a group that includes employees of
the National Institute of Environmental Health Sciences (NIEHS),
National Institutes of Health (NIH) and the U.S. Food and Drug
Administration (FDA); however, the statements, opinions, or conclusions
contained herein do not necessarily represent the statements, opinions,
or conclusions of FDA, NIEHS, NIH or the United States government. Anne
Johnson is employed by MDB, Inc. under a contract to NIEHS
(HHSN273201100086U). The authors declare they have no actual or
potential competing financial interests.
NR 18
TC 18
Z9 18
U1 1
U2 20
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0890-6238
J9 REPROD TOXICOL
JI Reprod. Toxicol.
PD SEP
PY 2013
VL 40
BP 35
EP 40
DI 10.1016/j.reprotox.2013.05.010
PG 6
WC Reproductive Biology; Toxicology
SC Reproductive Biology; Toxicology
GA 197KE
UT WOS:000322849300005
PM 23747832
ER
PT J
AU Bhutani, D
Zonder, J
Valent, J
Tageja, N
Ayash, L
Deol, A
Al-Kadhimi, Z
Abrams, J
Lum, L
Ratanatharathorn, V
Uberti, J
Abidi, MH
AF Bhutani, Divaya
Zonder, Jeffrey
Valent, Jason
Tageja, Nishant
Ayash, Lois
Deol, Abhinav
Al-Kadhimi, Zaid
Abrams, Judith
Lum, Lawrence
Ratanatharathorn, Voravit
Uberti, Joseph
Abidi, Muneer H.
TI Evaluating the effects of lenalidomide induction therapy on peripheral
stem cells collection in patients undergoing autologous stem cell
transplant for multiple myeloma
SO SUPPORTIVE CARE IN CANCER
LA English
DT Article
DE Lenalidomide; Multiple myeloma; Peripheral stem cells collection
ID INITIAL THERAPY; MOBILIZATION; DEXAMETHASONE; ENGRAFTMENT; CHEMOTHERAPY;
THALIDOMIDE; TRIAL
AB Lenalidomide (LEN) is a relatively new and very effective therapy for multiple myeloma (MM). Prior LEN therapy is associated with an increased risk of peripheral blood stem cell collection (PBSC) failure, particularly with filgrastim (G-CSF) alone. We performed a retrospective chart review of 319 consecutive MM patients who underwent apheresis to collect PBSCs for the first autologous stem cell transplant (ASCT).
The median number of PBSCs collected in the LEN (+) group was significantly less than the LEN (-) group (6.34 vs. 7.52 x 10(6) CD34(+) cells/kg; p = 0.0004). In addition, the median number of apheresis sessions required for adequate PBSCs collection were significantly more in the LEN (+) group as compared to LEN (-) group (2 vs. 1 sessions; p = 0.002). In the LEN (+) group, there was a negative correlation between PBSCs collected and prior number of cycles of LEN (p = 0.0001). Rate of PBSC collection failure was 9 % in the LEN (+) group and 5 % in the LEN (-) group (p = 0.16). Only six patients who failed PBSC collection with G-CSF were able to collect adequate PBSCs with G-CSF + plerixafor. LEN exposure had no effect on neutrophil or platelet recovery post-ASCT.
Up to four cycles of LEN exposure have minimal negative impact on PBSC collection. Despite prolong exposure of LEN, PBSC collection was adequate for two ASCTs in the majority of patients and post-ASCT engraftment was not longer than expected; however, clinical relevance (complication rate, quality of life, cost) of prolonged LEN exposure on both PBSC and ASCT, should be evaluated in prospective clinical trials.
C1 [Bhutani, Divaya; Zonder, Jeffrey; Ayash, Lois; Deol, Abhinav; Al-Kadhimi, Zaid; Abrams, Judith; Lum, Lawrence; Ratanatharathorn, Voravit; Uberti, Joseph; Abidi, Muneer H.] Karmanos Canc Inst, Dept Bone Marrow Transplantat, Detroit, MI 48201 USA.
[Valent, Jason] Cleveland Clin, Cleveland, OH 44106 USA.
[Bhutani, Divaya; Ayash, Lois; Deol, Abhinav; Al-Kadhimi, Zaid; Abrams, Judith; Lum, Lawrence; Ratanatharathorn, Voravit; Uberti, Joseph; Abidi, Muneer H.] Wayne State Univ, Detroit, MI USA.
[Tageja, Nishant] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Abidi, MH (reprint author), Karmanos Canc Inst, Dept Bone Marrow Transplantat, 4100 John R,4 HWCRC,Rm 4257, Detroit, MI 48201 USA.
EM abidim@karmanos.org
OI Abidi, Muneer/0000-0002-9936-6031
FU NCI NIH HHS [P30 CA022453]
NR 20
TC 1
Z9 1
U1 0
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0941-4355
J9 SUPPORT CARE CANCER
JI Support. Care Cancer
PD SEP
PY 2013
VL 21
IS 9
BP 2437
EP 2442
DI 10.1007/s00520-013-1808-5
PG 6
WC Oncology; Health Care Sciences & Services; Rehabilitation
SC Oncology; Health Care Sciences & Services; Rehabilitation
GA 194IY
UT WOS:000322626600009
PM 23591714
ER
PT J
AU Waidyanatha, S
Johnson, JD
Hong, SP
Robinson, VG
Gibbs, S
Graves, SW
Hooth, MJ
Smith, CS
AF Waidyanatha, Suramya
Johnson, Jerry D.
Hong, S. Peter
Robinson, Veronica Godfrey
Gibbs, Seth
Graves, Steven W.
Hooth, Michelle J.
Smith, Cynthia S.
TI Toxicokinetics of alpha-thujone following intravenous and gavage
administration of alpha-thujone or alpha- and beta-thujone mixture in
male and female F344/N rats and B6C3F1 mice
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE Thujone; Gavage; Toxicokinetics; Bioavailability; Rodents; Neurotoxicity
ID ABSINTHE; MEDICINES; WORMWOOD; POISON; FOODS; SAGE
AB Plants containing thujone have widespread use and hence have significant human exposure. alpha-Thujone caused seizures in rodents following gavage administration. We investigated the toxicokinetics of alpha-thujone in male and female F344/N rats and B6C3F1 mice following intravenous and gavage administration of alpha-thujone or a mixture of alpha- and beta-thujone (which will be referred to as alpha,beta-thujone). Absorption of alpha-thujone following gavage administration was rapid without any dose-, species-, sex- or test article-related effect. Absolute bioavailability of alpha-thujone following administration of alpha-thujone or alpha,beta-thujone was generally higher in rats than in mice. In rats, females had higher bioavailability than males following administration of either test article although a sex difference was not observed in mice. C-max and AUC(infinity) increased greater than proportional to the dose in female rats following administration of alpha-thujone and in male and female mice following administration of alpha,beta-thujone suggesting possible saturation of elimination kinetics with increasing dose. Dose-adjusted AUC(infinity) for male and female rats was 5- to 15-fold and 3- to 24-fold higher than mice counterparts following administration of a-thujone and alpha,beta-thujone, respectively (p-value < 0.0001 for all comparisons). Following both intravenous and gavage administration, et-thujone was distributed to the brains of rats and mice with females, in general, having higher brain:plasma ratios than males. These data are in support of the observed toxicity of alpha-thujone and alpha,beta-thujone where females were more sensitive than males of both species to alpha-thujone-induced neurotoxicity. In general there was no difference in toxicokinetics between test articles when normalized to alpha-thujone concentration. Published by Elsevier Inc.
C1 [Waidyanatha, Suramya; Robinson, Veronica Godfrey; Hooth, Michelle J.; Smith, Cynthia S.] NIEHS, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Johnson, Jerry D.; Hong, S. Peter; Gibbs, Seth; Graves, Steven W.] Battelle Mem Inst, Columbus, OH 43201 USA.
RP Waidyanatha, S (reprint author), NIEHS, Div Natl Toxicol Program, 111 Alexander Dr,POB 12233,MD K2-07, Res Triangle Pk, NC 27709 USA.
EM waidyanathas@niehs.nih.gov
FU National Institute of Environmental Health Sciences (NIEHS), National
Institutes of Health, Department of Health and Human Services
[N01-ES-55551]
FX This study was conducted for the National Toxicology Program, National
Institute of Environmental Health Sciences (NIEHS), National Institutes
of Health, Department of Health and Human Services, under Contract No.
N01-ES-55551. The authors are grateful to Drs Michael DeVito and Chad
Blystone for their review of the manuscript.
NR 26
TC 3
Z9 4
U1 3
U2 22
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0041-008X
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD SEP 1
PY 2013
VL 271
IS 2
BP 216
EP 228
DI 10.1016/j.taap.2013.05.001
PG 13
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 200ST
UT WOS:000323091900010
PM 23669748
ER
PT J
AU Glineur, SF
Renshaw, RW
Percopo, CM
Dyer, KD
Dubovi, EJ
Domachowske, JB
Rosenberg, HF
AF Glineur, Stephanie F.
Renshaw, Randall W.
Percopo, Caroline M.
Dyer, Kimberly D.
Dubovi, Edward J.
Domachowske, Joseph B.
Rosenberg, Helene F.
TI Novel pneumoviruses (PnVs): Evolution and inflammatory pathology
SO VIROLOGY
LA English
DT Article
DE Inflammation; Neutrophil; Type I interferon; Chemokine
ID RESPIRATORY SYNCYTIAL VIRUS; MICE MUS-DOMESTICUS; PNEUMONIA VIRUS;
NATURAL HOST; RAT COLONIES; SUBGROUP-A; INFECTION; MOUSE; PVM;
IDENTIFICATION
AB A previous report of a novel pneumovirus (PnV) isolated from the respiratory tract of a dog described its significant homology to the rodent pathogen, pneumonia virus of mice (PVM). The original PnV-Ane4 pathogen replicated in and could be re-isolated in infectious state from mouse lung but elicited minimal mortality compared to PVM strain J3666. Here we assess phylogeny and physiologic responses to 10 new PnV isolates. The G/glycoprotein sequences of all PnVs include elongated amino-termini when compared to the characterized PVMs, and suggest division into groups A and B. While we observed significant differences in cytokine production and neutrophil recruitment to the lungs of BALB/c mice in response to survival doses (50 TCID50 units) of representative group A (114378-10-29-KY-F) and group B (7968-11-OK) PnVs, we observed no evidence for positive selection (dN > dS) among the PnV/PnV, PVM/PnV or PVM/PVM G/glycoprotein or F/fusion protein sequence pairs. Published by Elsevier Inc.
C1 [Glineur, Stephanie F.; Percopo, Caroline M.; Dyer, Kimberly D.; Rosenberg, Helene F.] NIAID, Natl Inst Hlth, Lab Allerg Dis, Inflammat Immunobiol Sect, Bethesda, MD 20892 USA.
[Renshaw, Randall W.; Dubovi, Edward J.] Cornell Univ, Coll Vet Med, Anim Hlth Diagnost Ctr, Ithaca, NY 14851 USA.
[Domachowske, Joseph B.] SUNY Upstate Med Univ, Dept Pediat, Syracuse, NY 13210 USA.
RP Rosenberg, HF (reprint author), NIAID, Natl Inst Hlth, Lab Allerg Dis, Inflammat Immunobiol Sect, Bethesda, MD 20892 USA.
EM hrosenberg@niaid.nih.gov
FU NIAID Division of Intramural Research Project [AI000943]; Huynen
Foundation (University of Liege, Belgium); Rotary Foundation; Rotary
International
FX The authors thank Ms. Melissa Laverack and Ms. Nancy Zylich, Animal
Health Diagnostic Center, College of Veterinary Medicine, Cornell
University, for research technical support. Work presented in this
manuscript is supported by funds from the NIAID Division of Intramural
Research Project #AI000943 to HFR. SG was an awardee of the Huynen
Foundation (University of Liege, Belgium) and the Rotary Foundation,
Rotary International.
NR 34
TC 7
Z9 7
U1 0
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD SEP 1
PY 2013
VL 443
IS 2
BP 257
EP 264
DI 10.1016/j.virol.2013.05.011
PG 8
WC Virology
SC Virology
GA 195FC
UT WOS:000322686700009
PM 23763766
ER
PT J
AU Castillo, BS
Nguyen, N
Wahed, A
Tholpady, A
AF Castillo, Brian S.
Nguyen, Nghia
Wahed, Amer
Tholpady, Ashok
TI Monoclonal Gammopathy Causing Acquired Fanconi Syndrome in a Preterm
Infant
SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Meeting Abstract
C1 [Castillo, Brian S.] UT Houston Med Sch, Houston, TX USA.
[Nguyen, Nghia; Wahed, Amer] Univ Texas Houston, Houston, TX USA.
[Tholpady, Ashok] NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL PATHOLOGY
PI CHICAGO
PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA
SN 0002-9173
EI 1943-7722
J9 AM J CLIN PATHOL
JI Am. J. Clin. Pathol.
PD SEP
PY 2013
VL 140
SU 1
MA 43
BP 43
EP 43
PG 1
WC Pathology
SC Pathology
GA V40HA
UT WOS:000209468500044
ER
PT J
AU Coakley, MF
Leerkes, MR
Barnett, J
Gabrielian, AE
Noble, K
Weber, MN
Huyen, Y
AF Coakley, Meghan F.
Leerkes, Maarten R.
Barnett, Jason
Gabrielian, Andrei E.
Noble, Karlynn
Weber, M. Nick
Huyen, Yentram
TI UNLOCKING THE POWER OF BIG DATA AT THE NATIONAL INSTITUTES OF HEALTH
SO BIG DATA
LA English
DT Article
AB The era of "big data'' presents immense opportunities for scientific discovery and technological progress, with the potential to have enormous impact on research and development in the public sector. In order to capitalize on these benefits, there are significant challenges to overcome in data analytics. The National Institute of Allergy and Infectious Diseases held a symposium entitled "Data Science: Unlocking the Power of Big Data'' to create a forum for big data experts to present and share some of the creative and innovative methods to gleaning valuable knowledge from an overwhelming flood of biological data. A significant investment in infrastructure and tool development, along with more and better-trained data scientists, may facilitate methods for assimilation of data and machine learning, to overcome obstacles such as data security, data cleaning, and data integration.
C1 [Coakley, Meghan F.; Leerkes, Maarten R.; Barnett, Jason; Gabrielian, Andrei E.; Noble, Karlynn; Weber, M. Nick; Huyen, Yentram] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, Bethesda, MD 20892 USA.
RP Huyen, Y (reprint author), NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, OSMO,OD,NIH, 10401 Fernwood Rd,Room 2A11,Mail Stop Code 4821, Bethesda, MD 20892 USA.
EM huyeny@niaid.nih.gov
FU Intramural NIH HHS [Z99 AI999999]
NR 8
TC 1
Z9 1
U1 2
U2 2
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 2167-6461
EI 2167-647X
J9 BIG DATA
JI Big Data
PD SEP
PY 2013
VL 1
IS 3
BP 183
EP 186
DI 10.1089/big.2013.0012
PG 4
WC Computer Science, Interdisciplinary Applications; Computer Science,
Theory & Methods
SC Computer Science
GA V42XJ
UT WOS:000209646200012
PM 27442200
ER
PT J
AU Linehan, WM
AF Linehan, W. Marston
TI Evaluation and screening for hereditary renal cell cancers
SO CUAJ-CANADIAN UROLOGICAL ASSOCIATION JOURNAL
LA English
DT Editorial Material
C1 NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, 10 Ctr Dr MSC 1107,CRC Room 1W-5940, Bethesda, MD 20892 USA.
EM WML@nih.gov
NR 4
TC 3
Z9 3
U1 0
U2 0
PU CANADIAN UROLOGICAL ASSOCIATION
PI DORVAL
PA 185 DORVAL AVENUE, STE 401, DORVAL, QC H9S 5J9, CANADA
SN 1911-6470
EI 1920-1214
J9 CUAJ-CAN UROL ASSOC
JI CUAJ-Can. Urol. Assoc. J.
PD SEP-OCT
PY 2013
VL 7
IS 9-10
BP 324
EP 325
DI 10.5489/cuaj.1685
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA AO9SW
UT WOS:000341698100035
PM 24319510
ER
PT J
AU de Koning, HJ
Plevritis, SK
Meza, R
ten Haaf, K
Munshi, VN
Pinsky, PF
Hazelton, WD
Feuer, EJ
McMahon, PM
AF de Koning, H. J.
Plevritis, S. K.
Meza, R.
ten Haaf, K.
Munshi, V. N.
Pinsky, P. F.
Hazelton, W. D.
Feuer, E. J.
McMahon, P. M.
CA CISNET Lung Modeling Grp
TI Benefits and harms of computed tomography lung cancer screening programs
for high risk populations - using evidence from the 2 largest randomized
controlled trials on lung cancer screening worldwide
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
C1 [de Koning, H. J.; ten Haaf, K.] Erasmus MC, Publ Hlth, Rotterdam, Netherlands.
[Plevritis, S. K.] Stanford Univ, Stanford, CA 94305 USA.
[Meza, R.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Munshi, V. N.; McMahon, P. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Pinsky, P. F.; Feuer, E. J.; CISNET Lung Modeling Grp] NCI, Bethesda, MD 20892 USA.
[Hazelton, W. D.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD SEP
PY 2013
VL 49
SU 3
MA LBA14
BP S7
EP S7
PG 1
WC Oncology
SC Oncology
GA V40HV
UT WOS:000209470600019
ER
PT J
AU Giaccone, G
Bazhenova, L
Nemunaitis, J
Juhasz, E
Ramlau, R
van den Heuvel, MM
Lal, R
Dunlop, DJ
Carrier, E
Fakhrai, H
AF Giaccone, G.
Bazhenova, L.
Nemunaitis, J.
Juhasz, E.
Ramlau, R.
van den Heuvel, M. M.
Lal, R.
Dunlop, D. J.
Carrier, E.
Fakhrai, H.
TI A phase III study of belagenpumatucel-L therapeutic tumor cell vaccine
for non-small cell lung cancer (NSCLC)
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
C1 [Giaccone, G.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Bazhenova, L.] Univ Calif San Diego, Med Oncol Branch, Moores Canc Ctr, Ctr Canc Res, La Jolla, CA USA.
[Nemunaitis, J.] Mary Crowley Med Res Ctr, Med Oncol Branch, Ctr Canc Res, Dallas, TX USA.
[Juhasz, E.] Koranyi Natl Inst TB & Pulmonol I & XIV, Pulmonol, Budapest, Hungary.
[Ramlau, R.] Ctr Lung Dis & TB, Pulmonol, Poznan, Poland.
[van den Heuvel, M. M.] Antoni van Leeuwenhoek Ziekenhuis, Pulmonol, Amsterdam, Netherlands.
[Lal, R.] Guys Hosp, Med Oncol, London SE1 9RT, England.
[Dunlop, D. J.] Glasgow Royal Infirm, Med Oncol, Glasgow G4 0SF, Lanark, Scotland.
[Carrier, E.; Fakhrai, H.] NovaRx Corp, Med Oncol, San Diego, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD SEP
PY 2013
VL 49
SU 3
MA LBA2
BP S2
EP S3
PG 2
WC Oncology
SC Oncology
GA V40HV
UT WOS:000209470600007
ER
PT J
AU Paoletti, X
Le Tourneau, C
Collette, L
Rizzo, E
Lacombe, D
Olmos, D
Siu, L
Percy, Y
Seymour, L
Kaye, SB
Verweij, J
Massard, C
Postel-Vinay, S
Soria, J
AF Paoletti, X.
Le Tourneau, C.
Collette, L.
Rizzo, E.
Lacombe, D.
Olmos, D.
Siu, L.
Percy, Y.
Seymour, L.
Kaye, S. B.
Verweij, J.
Massard, C.
Postel-Vinay, S.
Soria, J.
CA DLT-TARGETT DLT Toxicity
TI Towards new methods for the determination of dose limiting toxicities
and the assessment of the recommended dose for further studies of
non-cytotoxic agents
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
C1 [Massard, C.; Postel-Vinay, S.; Soria, J.] Inst Gustave Roussy, Dept Med, DITEP, Villejuif, France.
[Paoletti, X.] Inst Curie, Dept Stat, Paris, France.
[Le Tourneau, C.] Inst Curie, Dept Med Oncol, Paris, France.
[Collette, L.; Rizzo, E.] EORTC Headquarters, Dept Stat, Brussels, Belgium.
[Lacombe, D.] EORTC Headquarters, Brussels, Belgium.
[Olmos, D.] Spanish Natl Canc Res Ctr CNIO, Clin Res Programme, Prostate Canc & Genitourinary Tumours Clin Res Un, Madrid, Spain.
[Siu, L.] Princess Margaret Canc Ctr, Toronto, ON, Canada.
[Percy, Y.] NCI, Bethesda, MD 20892 USA.
[Percy, Y.] NCI, Div Canc Treatment, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Seymour, L.] NCIC Clin Trials Grp, Kingston, ON, Canada.
[Kaye, S. B.] Royal Marsden Hosp, Inst Canc Res, Drug Dev Unit, Sutton, Surrey, England.
[Verweij, J.] Erasmus MC Canc Inst, Dept Med Oncol, Rotterdam, Netherlands.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD SEP
PY 2013
VL 49
SU 3
MA LBA8
BP S5
EP S5
PG 1
WC Oncology
SC Oncology
GA V40HV
UT WOS:000209470600013
ER
PT J
AU Ahuja, S
Henneke, I
Knudsen, L
Gochuico, BR
Ruppert, C
Ochs, M
Korfei, M
Seeger, W
Guenther, A
Mahavadi, P
AF Ahuja, Saket
Henneke, Ingrid
Knudsen, Lars
Gochuico, Bernadette R.
Ruppert, Clemens
Ochs, Matthias
Korfei, Martina
Seeger, Werner
Guenther, Andreas
Mahavadi, Poornima
TI Deficient autophagy in Hermansky-Pudlak syndrome associated interstitial
pneumonia (HPSIP)
SO EUROPEAN RESPIRATORY JOURNAL
LA English
DT Meeting Abstract
DE Interstitial lung disease; Epithelial cell; Animal models
C1 [Ahuja, Saket; Henneke, Ingrid; Ruppert, Clemens; Korfei, Martina; Seeger, Werner; Guenther, Andreas; Mahavadi, Poornima] Univ Giessen, Dept Internal Med, D-35392 Giessen, Germany.
[Ahuja, Saket; Henneke, Ingrid; Ruppert, Clemens; Korfei, Martina; Seeger, Werner; Guenther, Andreas; Mahavadi, Poornima] Marburg Lung Ctr, D-35392 Giessen, Germany.
[Knudsen, Lars; Ochs, Matthias] Hannover Med Sch, Inst Funct & Appl Anat, Hannover, Germany.
[Gochuico, Bernadette R.] NHGRI, Med Genet Branch, Bethesda, MD 20892 USA.
[Ochs, Matthias] German Ctr Lung Res, DZL, Hannover, Germany.
[Seeger, Werner; Guenther, Andreas] German Ctr Lung Res, DZL, Giessen, Germany.
[Guenther, Andreas] Agaples Lung Clin, Waldhof Elgershausen, Greifenstein, Germany.
EM saket.biotech@gmail.com; Ingrid.Henneke@innere.med.uni-giessen.de;
Knudsen.Lars@mh-hannover.de; gochuicb@mail.nih.gov;
Clemens.Ruppert@innere.med.uni-giessen.de; ochs.matthias@mh-hannover.de;
Martina.Korfei@innere.med.uni-giessen.de;
werner.seeger@innere.med.uni-giessen.de;
andreas.guenther@innere.med.uni-giessen.de;
Poornima.Mahavadi@innere.med.uni-giessen.de
NR 0
TC 0
Z9 0
U1 1
U2 1
PU EUROPEAN RESPIRATORY SOC JOURNALS LTD
PI SHEFFIELD
PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND
SN 0903-1936
EI 1399-3003
J9 EUR RESPIR J
JI Eur. Resp. J.
PD SEP 1
PY 2013
VL 42
SU 57
MA 4838
PG 2
WC Respiratory System
SC Respiratory System
GA V38VH
UT WOS:000209370404479
ER
PT J
AU Geraghty, P
Hardigan, A
Wallace, A
Mirochnitchenko, O
Thankachen, J
D'Armiento, J
Foronjy, R
AF Geraghty, Patrick
Hardigan, Andrew
Wallace, Alison
Mirochnitchenko, Oleg
Thankachen, Jincy
D'Armiento, Jeanine
Foronjy, Robert
TI The GPx1-PTP1B-PP2A axis: A key determinant of airway inflammation and
alveolar destruction
SO EUROPEAN RESPIRATORY JOURNAL
LA English
DT Meeting Abstract
DE COPD - mechanism; Anti-inflammatory; Cell biology
C1 [Geraghty, Patrick; Hardigan, Andrew; Thankachen, Jincy; Foronjy, Robert] Columbia Univ, St Lukes Roosevelt Hosp Ctr, Med, New York, NY 10019 USA.
[Wallace, Alison] Univ British Columbia, Surg, Vancouver, BC V6T 1Z3, Canada.
[Mirochnitchenko, Oleg] NIH, Div Comparat Med, Bethesda, MD 20892 USA.
[D'Armiento, Jeanine] Columbia Univ, Med Ctr, Anesthesiol, New York, NY 10032 USA.
EM pgeraghty@chpnet.org; andrewhardigan@gmail.com; amrwallace@gmail.com;
oleg.mirochnitchenko@nih.gov; jincy.thankachen@gmail.com;
jmd12@columbia.edu; rforonjy@chpnet.org
NR 0
TC 0
Z9 0
U1 1
U2 1
PU EUROPEAN RESPIRATORY SOC JOURNALS LTD
PI SHEFFIELD
PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND
SN 0903-1936
EI 1399-3003
J9 EUR RESPIR J
JI Eur. Resp. J.
PD SEP 1
PY 2013
VL 42
SU 57
MA 3004
PG 1
WC Respiratory System
SC Respiratory System
GA V38VH
UT WOS:000209370400208
ER
PT J
AU Havland, I
Lundholm, C
Lichtenstein, P
Niderheiser, J
Ganiban, J
Spotts, E
Walum, H
Reiss, D
Almqvist, C
AF Havland, Ida
Lundholm, Cecilia
Lichtenstein, Paul
Niderheiser, Jenae
Ganiban, Jody
Spotts, Erica
Walum, Hasse
Reiss, David
Almqvist, Catarina
TI Maternal anxiety and adolescent asthma: Children of twin design suggest
familial effects
SO EUROPEAN RESPIRATORY JOURNAL
LA English
DT Meeting Abstract
DE Asthma - mechanism; Environment; Genetics
C1 [Havland, Ida; Lundholm, Cecilia; Lichtenstein, Paul; Walum, Hasse; Almqvist, Catarina] Karolinska Inst, Epidemiol & Biostat, Stockholm, Sweden.
[Niderheiser, Jenae] Penn State Univ, Psychol, University Pk, PA 16802 USA.
[Ganiban, Jody] George Washington Univ, Psychol, Washington, DC USA.
[Spotts, Erica] NIH, Div Behav & Social Res, Bethesda, MD 20892 USA.
[Reiss, David] Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT USA.
[Almqvist, Catarina] Astrid Lindgren Childrens Hosp, Womens & Childrens Hlth, Stockholm, Sweden.
EM ida.havland@gmail.com; cecilia.lundholm@ki.se; Paul.Lichtenstein@ki.se;
jenaemn@psu.edu; jmganiban@gmail.com; spottse@od.nih.gov;
hasse.walum@ki.se; dxreiss@earthlink.net; Catarina.Almqvist@ki.se
NR 0
TC 0
Z9 0
U1 0
U2 0
PU EUROPEAN RESPIRATORY SOC JOURNALS LTD
PI SHEFFIELD
PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND
SN 0903-1936
EI 1399-3003
J9 EUR RESPIR J
JI Eur. Resp. J.
PD SEP 1
PY 2013
VL 42
SU 57
MA 7216
PG 1
WC Respiratory System
SC Respiratory System
GA V38VH
UT WOS:000209370401223
ER
PT J
AU Kistemaker, L
Bos, S
Hylkema, M
Hiemstra, P
Wess, J
Meurs, H
Kerstjens, H
Gosens, R
AF Kistemaker, Loes
Bos, Sophie
Hylkema, Machteld
Hiemstra, Pieter
Wess, Jurgen
Meurs, Herman
Kerstjens, Huib
Gosens, Reinoud
TI The muscarinic M-3 receptor regulates allergen-induced airway remodeling
in mice
SO EUROPEAN RESPIRATORY JOURNAL
LA English
DT Meeting Abstract
DE Asthma - mechanism; Pharmacology; Inflammation
C1 [Kistemaker, Loes; Bos, Sophie; Meurs, Herman; Gosens, Reinoud] Univ Groningen, Mol Pharmacol, Groningen, Netherlands.
[Hylkema, Machteld] Univ Med Ctr Groningen, Pathol & Med Biol, NL-9713 AV Groningen, Netherlands.
[Hiemstra, Pieter] Leiden Univ, Med Ctr, Pulmonol, Leiden, Netherlands.
[Wess, Jurgen] NIDDK, Bioorgan Chem, Bethesda, MD 20892 USA.
[Kerstjens, Huib] Univ Med Ctr Groningen, Resp Med, NL-9713 AV Groningen, Netherlands.
[Kistemaker, Loes; Bos, Sophie; Hylkema, Machteld; Meurs, Herman; Kerstjens, Huib; Gosens, Reinoud] Univ Groningen, GRIAC Res Inst, Groningen, Netherlands.
EM l.e.m.kistemaker@rug.nl; i.s.t.bos@rug.nl; m.n.hylkema@umcg.nl;
p.s.hiemstra@lumc.nl; jurgenw@helix.nih.gov; h.meurs@rug.nl;
h.a.m.kerstjens@umcg.nl; r.gosens@rug.nl
NR 0
TC 0
Z9 0
U1 0
U2 0
PU EUROPEAN RESPIRATORY SOC JOURNALS LTD
PI SHEFFIELD
PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND
SN 0903-1936
EI 1399-3003
J9 EUR RESPIR J
JI Eur. Resp. J.
PD SEP 1
PY 2013
VL 42
SU 57
MA 1067
PG 1
WC Respiratory System
SC Respiratory System
GA V38VH
UT WOS:000209370403419
ER
PT J
AU Moberg, M
Palchamy, E
Wouters, E
Vestbo, J
Ferrucci, L
Rutten, E
AF Moberg, Mia
Palchamy, Elango
Wouters, Emiel
Vestbo, Jorgen
Ferrucci, Luigi
Rutten, Erica
TI Relationship between vitamin D status and lung function in the Baltimore
longitudinal study of aging
SO EUROPEAN RESPIRATORY JOURNAL
LA English
DT Meeting Abstract
DE Epidemiology; Biomarkers; Lung growth/development
C1 [Moberg, Mia] Hvidovre Univ Hosp, Dept Resp Med, DK-2650 Hvidovre, Denmark.
[Palchamy, Elango; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21225 USA.
[Wouters, Emiel; Rutten, Erica] Ctr Expertise Chron Organ Failure CIRO, Program Dev Ctr, NL-6085 Horn, Netherlands.
[Vestbo, Jorgen] Odense Univ Hosp, Dept Resp Med, DK-5000 Odense, Denmark.
EM miamoberg@hotmail.com; elangop@mail.nih.gov; e.wouters@mumc.nl;
joergen.vestbo@ouh.regionsyddanmark.dk; ferruccilu@mail.nih.gov;
ericarutten@ciro-horn.nl
NR 0
TC 0
Z9 0
U1 0
U2 0
PU EUROPEAN RESPIRATORY SOC JOURNALS LTD
PI SHEFFIELD
PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND
SN 0903-1936
EI 1399-3003
J9 EUR RESPIR J
JI Eur. Resp. J.
PD SEP 1
PY 2013
VL 42
SU 57
MA 1104
PG 1
WC Respiratory System
SC Respiratory System
GA V38VH
UT WOS:000209370401164
ER
EF