FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Janne, PA
Shaw, AT
Giaccone, G
Camidge, DR
Shreeve, SM
Goldberg, Z
Tang, Y
Solomon, B
AF Janne, P. A.
Shaw, A. T.
Giaccone, G.
Camidge, D. R.
Shreeve, S. M.
Goldberg, Z.
Tang, Y.
Solomon, B.
TI PHASE I TRIAL OF IRREVERSIBLE PAN-ERBB INHIBITOR DACOMITINIB (DAC) IN
COMBINATION WITH ALK/MET INHIBITOR CRIZOTINIB (CRIZ) IN PREVIOUSLY
TREATED ADVANCED NON-SMALL CELL LUNG CANCER (NSCLC)
SO ANNALS OF ONCOLOGY
LA English
DT Meeting Abstract
CT 37th Congress of the European-Society-for-Medical-Oncology (ESMO)
CY SEP 28-OCT 02, 2012
CL Vienna, AUSTRIA
SP European Soc Med Oncol (ESMO)
C1 [Janne, P. A.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Shaw, A. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Giaccone, G.] NCI, Thorac Oncol Sect, Bethesda, MD 20892 USA.
[Camidge, D. R.] Univ Colorado, Ctr Canc, Aurora, CO USA.
[Shreeve, S. M.; Goldberg, Z.; Tang, Y.] Pfizer Oncol, Res & Dev, La Jolla, CA USA.
[Solomon, B.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia.
NR 0
TC 1
Z9 1
U1 0
U2 4
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 2012
VL 23
SU 9
BP 423
EP 423
PG 1
WC Oncology
SC Oncology
GA 014XL
UT WOS:000309409002225
ER
PT J
AU Reck, M
Hassan, R
Jahan, T
Kindler, HL
Bazhenova, L
Fatato, P
Heyburn, JW
Parno, J
Maltzman, JD
Wallin, B
AF Reck, M.
Hassan, R.
Jahan, T.
Kindler, H. L.
Bazhenova, L.
Fatato, P.
Heyburn, J. W.
Parno, J.
Maltzman, J. D.
Wallin, B.
TI A MULTI-CENTER PHASE II CLINICAL TRIAL OF THE CHIMERIC ANTI-MESOTHELIN
MONOCLONAL ANTIBODY AMATUXIMAB IN COMBINATION WITH CHEMOTHERAPY FOR
FRONTLINE THERAPY OF MALIGNANT PLEURAL MESOTHELIOMA: UPDATED CLINICAL
OUTCOMES AND CORRELATIVE STUDIES
SO ANNALS OF ONCOLOGY
LA English
DT Meeting Abstract
CT 37th Congress of the European-Society-for-Medical-Oncology (ESMO)
CY SEP 28-OCT 02, 2012
CL Vienna, AUSTRIA
SP European Soc Med Oncol (ESMO)
C1 [Reck, M.] Krankenhaus Grosshansdorf, Grosshansdorf, Germany.
[Hassan, R.] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Jahan, T.] Univ Calif San Francisco, Div Hematol Oncol, San Francisco, CA 94143 USA.
[Kindler, H. L.] Univ Chicago, Div Oncol, Chicago, IL 60637 USA.
[Bazhenova, L.] UCSD Moores Canc Ctr, La Jolla, CA USA.
[Fatato, P.; Heyburn, J. W.; Parno, J.; Maltzman, J. D.; Wallin, B.] Morphotek, Oncol, Exton, PA USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
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 2012
VL 23
SU 9
BP 493
EP 493
PG 1
WC Oncology
SC Oncology
GA 014XL
UT WOS:000309409002451
ER
PT J
AU Foster, BL
AF Foster, Brian L.
TI Methods for studying tooth root cementum by light microscopy
SO INTERNATIONAL JOURNAL OF ORAL SCIENCE
LA English
DT Review
DE bone; bone sialoprotein; cementum; dentin; dentin matrix protein 1;
osteopontin; periodontal ligament; tooth development
ID ALKALINE-PHOSPHATASE; PERIODONTAL-LIGAMENT; HUMAN TEETH;
EXTRACELLULAR-MATRIX; ELECTRON-MICROSCOPY; RAT CEMENTUM; DENTIN; BONE;
OSTEOPONTIN; TISSUE
AB The tooth root cementum is a thin, mineralized tissue covering the root dentin that is present primarily as acellular cementum on the cervical root and cellular cementum covering the apical root. While cementum shares many properties in common with bone and dentin, it is a unique mineralized tissue and acellular cementum is critical for attachment of the tooth to the surrounding periodontal ligament (PDL). Resources for methodologies for hard tissues often overlook cementum and approaches that may be of value for studying this tissue. To address this issue, this report offers detailed methodology, as well as comparisons of several histological and immunohistochemical stains available for imaging the cementum-PDL complex by light microscopy. Notably, the infrequently used Alcian blue stain with nuclear fast red counterstain provided utility in imaging cementum in mouse, porcine and human teeth. While no truly unique extracellular matrix markers have been identified to differentiate cementum from the other hard tissues, immunohistochemistry for detection of bone sialoprotein (BSP), osteopontin (OPN), and dentin matrix protein 1 (DMP1) is a reliable approach for studying both acellular and cellular cementum and providing insight into developmental biology of these tissues. Histological and immunohistochemical approaches provide insight on developmental biology of cementum. International Journal of Oral Science (2012) 4, 119-128; doi:10.1038/ijos.2012.57; published online 21 September 2012
C1 [Foster, Brian L.] Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, NIH, Bethesda, MD USA.
RP Foster, BL (reprint author), 9000 Rockville Pike,Bldg 50,Room 4120, Bethesda, MD 20892 USA.
EM Brian.Foster@nih.gov
RI Foster, Brian/H-8375-2015
OI Foster, Brian/0000-0003-3444-0576
FU Intramural Research Program of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases of the National Institutes of Health
FX This research was supported (in part) by the Intramural Research Program
of the National Institute of Arthritis and Musculoskeletal and Skin
Diseases of the National Institutes of Health. Thanks to Dr Martha
Somerman (NIAMS, NIH, Bethesda, MD, USA) and Dr Tracy Popowics
(University of Washington School of Dentistry, Seattle, WA, USA) for
critically reading and providing editorial suggestions on the
manuscript. Thanks to Jirawan Wade (University of Washington School of
Dentistry) for histological sectioning of mouse tissues. Thanks to Dr
Tracy Popowics for preparing and providing porcine tissue samples, and
Dr Kuang-Dah Yeh (University of Washington School of Dentistry) for
porcine tissue processing and sectioning. Thanks to Dr Jose Luis Millan
(Sanford Burnham Institute, La Jolla, CA, USA) for providing Alp! mice.
Thanks to Dr Francisco H Nociti and Cristiane R Salmon (Campinas State
University, Piracicaba, SP, Brazil) for mouse tissues for DMP1 IHC.
NR 50
TC 25
Z9 26
U1 2
U2 16
PU SICHUAN UNIV
PI CHENGDU
PA SICHUAN UNIV, CHENGDU, SICHUAN, 610064 00000, PEOPLES R CHINA
SN 1674-2818
J9 INT J ORAL SCI
JI Int. J. Oral Sci.
PD SEP
PY 2012
VL 4
IS 3
BP 119
EP 128
DI 10.1038/ijos.2012.57
PG 10
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 020ZE
UT WOS:000309854300001
PM 22996273
ER
PT J
AU Bowles, EJA
Wellman, R
Feigelson, HS
Onitilo, AA
Freedman, AN
Delate, T
Allen, LA
Nekhlyudov, L
Goddard, KAB
Davis, RL
Habel, LA
Yood, MU
McCarty, C
Magid, DJ
Wagner, EH
AF Bowles, Erin J. Aiello
Wellman, Robert
Feigelson, Heather Spencer
Onitilo, Adedayo A.
Freedman, Andrew N.
Delate, Thomas
Allen, Larry A.
Nekhlyudov, Larissa
Goddard, Katrina A. B.
Davis, Robert L.
Habel, Laurel A.
Yood, Marianne Ulcickas
McCarty, Catherine
Magid, David J.
Wagner, Edward H.
CA Pharmacovigilance Study Team
TI Risk of Heart Failure in Breast Cancer Patients After Anthracycline and
Trastuzumab Treatment: A Retrospective Cohort Study
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID PLUS ADJUVANT CHEMOTHERAPY; OLDER WOMEN; CLINICAL-TRIALS; CARDIAC
SAFETY; CYCLOPHOSPHAMIDE; EPIRUBICIN; THERAPY; RECOMMENDATIONS;
CARDIOTOXICITY; METHOTREXATE
AB Clinical trials demonstrated that women treated for breast cancer with anthracycline or trastuzumab are at increased risk for heart failure and/or cardiomyopathy (HF/CM), but the generalizability of these findings is unknown. We estimated real-world adjuvant anthracycline and trastuzumab use and their associations with incident HF/CM.
We conducted a population-based, retrospective cohort study of 12 500 women diagnosed with incident, invasive breast cancer from January 1, 1999 through December 31, 2007, at eight integrated Cancer Research Network health systems. Using administrative procedure and pharmacy codes, we identified anthracycline, trastuzumab, and other chemotherapy use. We identified incident HF/CM following chemotherapy initiation and assessed risk of HF/CM with time-varying chemotherapy exposures vs no chemotherapy. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for age at diagnosis, stage, Cancer Research Network site, year of diagnosis, radiation therapy, and comorbidities.
Among 12 500 women (mean age = 60 years, range = 2299 years), 29.6% received anthracycline alone, 0.9% received trastuzumab alone, 3.5% received anthracycline plus trastuzumab, 19.5% received other chemotherapy, and 46.5% received no chemotherapy. Anthracycline and trastuzumab recipients were younger, with fewer comorbidities than recipients of other chemotherapy or none. Compared with no chemotherapy, the risk of HF/CM was higher in patients treated with anthracycline alone (adjusted HR = 1.40, 95% CI = 1.11 to 1.76), although the increased risk was similar to other chemotherapy (adjusted HR = 1.49, 95% CI = 1.25 to 1.77); the risk was highly increased in patients treated with trastuzumab alone (adjusted HR = 4.12, 95% CI = 2.30 to 7.42) or anthracycline plus trastuzumab (adjusted HR = 7.19, 95% CI = 5.00 to 10.35).
Anthracycline and trastuzumab were primarily used in younger, healthier women and associated with increased HF/CM risk compared with no chemotherapy. This population-based observational study complements findings from clinical trials on cancer treatment safety.
C1 [Bowles, Erin J. Aiello; Wellman, Robert; Wagner, Edward H.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98101 USA.
[Feigelson, Heather Spencer; Delate, Thomas; Magid, David J.] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA.
[Onitilo, Adedayo A.; McCarty, Catherine] Marshfield Clin Weston Ctr, Dept Hematol Oncol, Weston, WI USA.
[Onitilo, Adedayo A.] Marshfield Clin Res Fdn, Marshfield, WI USA.
[Freedman, Andrew N.] NCI, Bethesda, MD 20892 USA.
[Allen, Larry A.] Univ Colorado, Div Cardiol, Aurora, CO USA.
[Nekhlyudov, Larissa] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA.
[Nekhlyudov, Larissa] Harvard Pilgrim Hlth Care Inst, Boston, MA USA.
[Nekhlyudov, Larissa] Harvard Vanguard Med Associates, Dept Med, Boston, MA USA.
[Goddard, Katrina A. B.] Kaiser Permanente NW, Ctr Hlth Res, Portland, OR USA.
[Davis, Robert L.] Kaiser Permanente Georgia, Ctr Hlth Res SE, Atlanta, GA USA.
[Habel, Laurel A.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA.
[Yood, Marianne Ulcickas] Henry Ford Hosp & Hlth Syst, Dept Res, Detroit, MI USA.
[McCarty, Catherine] Essentia Inst Rural Hlth, Duluth, MN USA.
RP Bowles, EJA (reprint author), Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, 1730 Minor Ave,Ste 1600, Seattle, WA 98101 USA.
EM bowles.e@ghc.org
OI Ulcickas Yood, Marianne/0000-0003-4204-0871
FU National Cancer Institute at the National Institutes of Health [U19 CA
79689]
FX This work was supported by the National Cancer Institute at the National
Institutes of Health through an administrative supplement to the Cancer
Research Network (grant number U19 CA 79689 to EHW).
NR 40
TC 147
Z9 149
U1 1
U2 11
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD SEP
PY 2012
VL 104
IS 17
BP 1293
EP 1305
DI 10.1093/jnci/djs317
PG 13
WC Oncology
SC Oncology
GA 002PJ
UT WOS:000308544000008
PM 22949432
ER
PT J
AU Marshall, JCA
Collins, JW
Nakayama, J
Horak, CE
Liewehr, DJ
Steinberg, SM
Albaugh, M
Vidal-Vanaclocha, F
Palmieri, D
Barbier, M
Murone, M
Steeg, PS
AF Marshall, Jean-Claude A.
Collins, Joshua W.
Nakayama, Joji
Horak, Christine E.
Liewehr, David J.
Steinberg, Seth M.
Albaugh, Mary
Vidal-Vanaclocha, Fernando
Palmieri, Diane
Barbier, Maryse
Murone, Maximilien
Steeg, Patricia S.
TI Effect of Inhibition of the Lysophosphatidic Acid Receptor 1 on
Metastasis and Metastatic Dormancy in Breast Cancer
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID PROTEIN-COUPLED RECEPTORS; GREEN FLUORESCENT PROTEIN; KINASE
ALPHA-ISOFORM; CARCINOMA-CELL-LINE; IN-VITRO; SUPPRESSOR PROTEINS;
DIPHOSPHATE KINASE; TUMOR-GROWTH; ADENOCARCINOMA CELLS;
SIGNAL-TRANSDUCTION
AB Previous studies identified the human nonmetastatic gene 23 (NME1, hereafter Nm23-H1) as the first metastasis suppressor gene. An inverse relationship between Nm23-H1 and expression of lysophosphatidic acid receptor 1 gene (LPAR1, also known as EDG2 or hereafter LPA1) has also been reported. However, the effects of LPA1 inhibition on primary tumor size, metastasis, and metastatic dormancy have not been investigated.
The LPA1 inhibitor Debio-0719 or LPA1 short hairpinned RNA (shRNA) was used. Primary tumor size and metastasis were investigated using the 4T1 spontaneous metastasis mouse model and the MDA-MB-231T experimental metastasis mouse model (n = 13 mice per group). Proliferation and p38 intracellular signaling in tumors and cell lines were determined by immunohistochemistry and western blot to investigate the effects of LPA1 inhibition on metastatic dormancy. An analysis of variance-based two-tailed t test was used to determine a statistically significant difference between treatment groups.
In the 4T1 spontaneous metastasis mouse model, Debio-0719 inhibited the metastasis of 4T1 cells to the liver (mean = 25.2 liver metastases per histologic section for vehicle-treated mice vs 6.8 for Debio-0719-treated mice, 73.0% reduction, P < .001) and lungs (mean = 6.37 lesions per histologic section for vehicle-treated mice vs 0.73 for Debio-0719-treated mice, 88.5% reduction, P < .001), with no effect on primary tumor size. Similar results were observed using the MDA-MB-231T experimental pulmonary metastasis mouse model. LPA1 shRNA also inhibited metastasis but did not affect primary tumor size. In 4T1 metastases, but not primary tumors, expression of the proliferative markers Ki67 and pErk was reduced by Debio-0719, and phosphorylation of the p38 stress kinase was increased, indicative of metastatic dormancy.
The data identify Debio-0719 as a drug candidate with metastasis suppressor activity, inducing dormancy at secondary tumor sites.
C1 [Marshall, Jean-Claude A.; Collins, Joshua W.; Nakayama, Joji; Horak, Christine E.; Palmieri, Diane; Steeg, Patricia S.] NCI, Womens Canc Sect, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Liewehr, David J.; Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA.
[Albaugh, Mary] NCI, Inst Appl Mol Med, Lab Anim Sci Program, SAIC Frederick, Frederick, MD 21701 USA.
[Vidal-Vanaclocha, Fernando] CEU San Pablo Univ, Sch Med, Madrid, Spain.
[Vidal-Vanaclocha, Fernando] Hosp Madrid Sci Fdn, Madrid, Spain.
[Barbier, Maryse; Murone, Maximilien] Debiopharm SA, Lausanne, Switzerland.
RP Steeg, PS (reprint author), NIH, Bldg 37,Rm 1122, Bethesda, MD 20892 USA.
EM steegp@mail.nih.gov
RI Palmieri, Diane/B-4258-2015
FU National Cancer Institute and Breast Cancer Research Stamp Fund; ISCIII
[ADE09/90041]; Burdinola Professorship on Molecular Medicine
FX Intramural program of the National Cancer Institute and Breast Cancer
Research Stamp Fund awarded through competitive peer review by the
National Cancer Institute ( to PSS); ISCIII (ADE09/90041) and the
Burdinola Professorship on Molecular Medicine ( to FV-V).
NR 98
TC 40
Z9 41
U1 0
U2 13
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD SEP
PY 2012
VL 104
IS 17
BP 1306
EP 1319
DI 10.1093/jnci/djs319
PG 14
WC Oncology
SC Oncology
GA 002PJ
UT WOS:000308544000009
PM 22911670
ER
PT J
AU Pal, RK
Yasmin, H
Nahar, L
Datta, BK
Chowdhury, AA
Kundu, JK
Bachar, SC
Sarker, SD
AF Pal, Rajib Kumar
Yasmin, Hasina
Nahar, Lutfun
Datta, Bidyut Kanti
Chowdhury, Abul Kalam Azad
Kundu, Joydeb Kumar
Bachar, Sitesh Chandra
Sarker, Satyajit Dey
TI Synthesis of 5,6-Dichloroindan-1-Acids and their Tetrazolyl Derivatives
as Analgesic and Anti-inflammatory Agents
SO MEDICINAL CHEMISTRY
LA English
DT Article
DE Indan acids; Indanyl tetrazoles; 5,6-dichloroindan-1-carboxylic acid;
5,6-dichloroindan-1-acetic Acid; 5-(5 ',6 '-dichloroindan-1
'-yl)-tetrazole; 5-(5 ',6 '-dichloroindan-1 '-yl)-methyltetrazole;
Carrageenan; Analgesic activity; Anti-inflammatory activity
ID BIOLOGICAL EVALUATION; AMIDE DERIVATIVES; ACID; CARRAGEENIN; RAT;
5-(INDAN-1'-YL)METHYLTETRAZOLES; 5-(INDAN-1'-YL)TETRAZOLES; EDEMA; PAW
AB Indan derivatives, namely, 5-(5',6'-dichloroindan-1'-yl)-tetrazole (12a) and 5-(5', 6'-dichloroindan-1'-yl)methyltetrazole (12b), were synthesized conveniently from 5,6-dichloroindan-1-carboxylic acid (9a) and 5,6-dichloroindan-1-acetic acid (9b), respectively, as potential analgesic and anti-inflammatory agents. The analgesic and anti-inflammatory properties of 9a, 9b, 12a and 12b were evaluated by the acetic acid induced writhing in Swiss albino mice and the carrageenan-induced rat paw edema models, respectively. Compounds 9a and 12a exhibited significant analgesic activity with the doses of 50 and 100 mg/kg body weight, comparable to that of the positive controls, phenylbutazone, indomethacin and aminopyrine. The anti-inflammatory potencies of 9a and 12a were also comparable to that of the positive control, phenylbutazone. Compounds 9b and 12b showed analgesic and anti-inflammatory activities, but were weaker than that of compounds 9a and 12a.
C1 [Sarker, Satyajit Dey] Wolverhampton Univ, Dept Pharm, Sch Appl Sci, Wolverhampton WV1 1LY, W Midlands, England.
[Pal, Rajib Kumar] NIA, NIH, Baltimore, MD 21224 USA.
[Yasmin, Hasina] State Univ Bangladesh, Dept Pharm, Dhaka 1209, Bangladesh.
[Nahar, Lutfun] De Montfort Univ, Leicester Sch Pharm, Leicester LE1 9BH, Leics, England.
[Datta, Bidyut Kanti; Kundu, Joydeb Kumar; Bachar, Sitesh Chandra] Univ Dhaka, Fac Pharm, Dept Pharmaceut Technol, Dhaka 1000, Bangladesh.
[Chowdhury, Abul Kalam Azad] Univ Dhaka, Fac Pharm, Dept Clin Pharm & Pharmacol, Dhaka 1000, Bangladesh.
RP Sarker, SD (reprint author), Wolverhampton Univ, Dept Pharm, Sch Appl Sci, MA Bldg,Wulfruna St, Wolverhampton WV1 1LY, W Midlands, England.
EM S.Sarker@wlv.ac.uk
FU Ministry of Science and Technology, Government of Bangladesh, Dhaka
[BPROMA/SHA-9/B: ANU:/2000/339]
FX The authors are grateful to the Ministry of Science and Technology,
Government of Bangladesh, Dhaka, for granting a special allocation No.
BPROMA/SHA-9/B: ANU:/2000/339 dt 22/05/2001 to perform some aspects of
this project. Some of the MS analyses were performed at the EPSRC
National Mass Spectrometry Service Centre in Swansea, Wales, UK.
NR 33
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U1 0
U2 5
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1573-4064
J9 MED CHEM
JI Med. Chem.
PD SEP
PY 2012
VL 8
IS 5
BP 874
EP 882
PG 9
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 018HH
UT WOS:000309650400013
PM 22741799
ER
PT J
AU Cecchi, F
Bottaro, DP
AF Cecchi, Fabiola
Bottaro, Donald P.
TI Novel Antagonists of Heparin Binding Growth Factors
SO ONCOTARGET
LA English
DT Editorial Material
ID RECEPTOR ACTIVATION; VEGF RECEPTOR; HEPATOCYTE; SULFATE; DOMAINS
C1 [Cecchi, Fabiola; Bottaro, Donald P.] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
RP Bottaro, DP (reprint author), NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
EM dbottaro@helix.nih.gov
RI Bottaro, Donald/F-8550-2010
OI Bottaro, Donald/0000-0002-5057-5334
NR 10
TC 1
Z9 1
U1 0
U2 1
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD SEP
PY 2012
VL 3
IS 9
BP 911
EP 912
PG 2
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 020MR
UT WOS:000309815300003
PM 22989865
ER
PT J
AU Zhang, F
Rothermund, K
Gangadharan, SB
Pommier, Y
Prochownik, EV
Lazo, JS
AF Zhang, Fang
Rothermund, Kristi
Gangadharan, Sajithlal B.
Pommier, Yves
Prochownik, Edward V.
Lazo, John S.
TI Phenotypic Screening Reveals Topoisomerase I as a Breast Cancer Stem
Cell Therapeutic Target
SO ONCOTARGET
LA English
DT Article
DE cancer stem cell; Topoisomerase I; small molecule inhibitor; compound
library screening
ID BETA-LAPACHONE; CARCINOMA-CELLS; CAMPTOTHECIN; IDENTIFICATION;
RESISTANCE; LEUKEMIA; PATHWAY; CYTOTOXICITY; INHIBITORS; POPULATION
AB Cancer stem cells (CSCs) are a subpopulation generally thought to be responsible for cancer initiation and progression. Because CSCs are often rare in the total tumor cell population and differentiate rapidly when grown in culture, it has been challenging to uncover compounds that selectively target CSCs. We previously described CSC-emulating cells derived from breast cancer cell lines that maintained a stable undifferentiated state. We optimized a phenotypic assay with these cells and screened 1,280-bioactive compounds, identifying five that preferentially inhibited CSC-like cell proliferation. Using a compound-guided target identification approach, we found high topoisomerase I (Topo I) expression levels in breast CSC-like cells and primary breast CSCs. Structurally unrelated small molecules targeting Topo I preferentially inhibited CSC-like cells. These results illustrate the substantial power of this CSC phenotypic screening platform and promote Topo I as a potential molecular therapeutic target for therapies aimed at expunging CSCs.
C1 [Lazo, John S.] Univ Virginia, Dept Pharmacol & Chem, Charlottesville, VA USA.
[Zhang, Fang; Rothermund, Kristi; Gangadharan, Sajithlal B.; Prochownik, Edward V.] Univ Pittsburgh, Sect Hematol Oncol, Childrens Hosp Pittsburgh UPMC, Pittsburgh, PA USA.
[Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Lazo, JS (reprint author), Univ Virginia, Dept Pharmacol & Chem, Charlottesville, VA USA.
EM lazo@virginia.edu
FU Susan G. Komen for the Cure(R) Research Program Postdoctoral Fellowship
[KG101468]
FX We thank Jean Latimer for providing the primary breast cancer cells.
Fang Zhang is supported by Susan G. Komen for the Cure (R) Research
Program Postdoctoral Fellowship (KG101468). This publication is in
memory of the late Merrill J. Egorin, who continues to inspire our
research.
NR 50
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U1 0
U2 5
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD SEP
PY 2012
VL 3
IS 9
BP 998
EP 1010
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 020MR
UT WOS:000309815300012
PM 22948175
ER
PT J
AU Vosters, JL
Roescher, N
Polling, EJ
Illei, GG
Tak, PP
AF Vosters, Jelle L.
Roescher, Nienke
Polling, Eline J.
Illei, Gabor G.
Tak, Paul P.
TI The expression of APRIL in Sjogren's syndrome: aberrant expression of
APRIL in the salivary gland
SO RHEUMATOLOGY
LA English
DT Article
DE Sjogren's syndrome; minor salivary glands; a proliferation inducing
ligand
ID TUMOR-NECROSIS-FACTOR; SYSTEMIC-LUPUS-ERYTHEMATOSUS; CELL-ACTIVATING
FACTOR; EPITHELIAL-CELLS; RHEUMATOID-ARTHRITIS; GENE-EXPRESSION; FACTOR
FAMILY; BAFF; STIMULATION; ASSOCIATION
AB Objective. A proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF) are B-cell-related mediators and may play a role in the pathogenesis in SS. In this descriptive study we assessed the expression of APRIL and BAFF in the minor salivary gland and serum from SS patients.
Methods. Paraffin-embedded minor salivary gland sections from SS patients, non-SS controls and healthy volunteers were analysed by immunohistochemistry. Digital image quantification was performed to evaluate the expression of BAFF, APRIL and transmembrane activator and CAML interactor. Furthermore, serum was analysed for soluble BAFF and APRIL levels by ELISA. All the data were also analysed for subjects with decreased and normal stimulated salivary flow independent of the classification.
Results. APRIL expression was lower in minor salivary gland biopsies from SS patients compared with healthy volunteers and to a lesser extent non-SS controls, whereas BAFF expression was similar in all groups. Soluble APRIL levels in serum were increased in SS patients and in subjects with decreased salivary flow independent of the classification.
Conclusion. APRIL salivary gland tissue levels are decreased, suggesting that targeting this cytokine locally in the salivary glands would not benefit SS patients. Moreover, the discrepancy between local and systemic levels is striking and future research should assess this in more detail.
C1 [Vosters, Jelle L.; Roescher, Nienke; Polling, Eline J.; Tak, Paul P.] Univ Amsterdam, Acad Med Ctr, Div Clin Immunol & Rheumatol, NL-1105 AZ Amsterdam, Netherlands.
[Vosters, Jelle L.; Roescher, Nienke; Illei, Gabor G.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA.
RP Vosters, JL (reprint author), Univ Amsterdam, Acad Med Ctr, Div Clin Immunol & Rheumatol, F4-105,Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
EM j.l.vosters@amc.uva.nl
FU Dutch Arthritis Association [NR 07-1-406]; National Institute of Dental
and Craniofacial Research (NIDCR)
FX This work was supported by a Dutch Arthritis Association grant (NR
07-1-406) to J.L.V. and National Institute of Dental and Craniofacial
Research (NIDCR) intramural research grant to N.R. and G.G.I.
NR 20
TC 6
Z9 6
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-0324
J9 RHEUMATOLOGY
JI RHEUMATOLOGY
PD SEP
PY 2012
VL 51
IS 9
BP 1557
EP 1562
DI 10.1093/rheumatology/kes080
PG 6
WC Rheumatology
SC Rheumatology
GA 992ME
UT WOS:000307779700007
PM 22562936
ER
PT J
AU Mitchell, JE
Selzer, F
Kalarchian, MA
Devlin, MJ
Strain, GW
Elder, KA
Marcus, MD
Wonderlich, S
Christian, NJ
Yanovski, SZ
AF Mitchell, James E.
Selzer, Faith
Kalarchian, Melissa A.
Devlin, Michael J.
Strain, Gladys W.
Elder, Katherine A.
Marcus, Marsha D.
Wonderlich, Steve
Christian, Nicholas J.
Yanovski, Susan Z.
TI Psychopathology before surgery in the Longitudinal Assessment of
Bariatric Surgery-3 (LABS-3) Psychosocial Study
SO SURGERY FOR OBESITY AND RELATED DISEASES
LA English
DT Article
DE Psychopathology; Eating disorders; Binge eating disorder
ID QUALITY-OF-LIFE; GASTRIC BYPASS-SURGERY; STRUCTURED CLINICAL INTERVIEWS;
TERM FOLLOW-UP; MORBIDLY OBESE; WEIGHT-LOSS; PSYCHIATRIC-DISORDERS;
EATING DISTURBANCES; DSM-IV; COMORBIDITY
AB Background: Current and previous psychopathology in bariatric surgery candidates is believed to be common. Accurate prevalence estimates, however, are difficult to obtain given that bariatric surgery candidates often wish to appear psychiatrically healthy when undergoing psychiatric evaluation for approval for surgery. Also, structured diagnostic assessments have been infrequently used.
Methods: The present report concerned 199 patients enrolled in the Longitudinal Assessment of Bariatric Surgery study, who also participated in the Longitudinal Assessment of Bariatric Surgery-3 psychopathology substudy. The setting was 3 university hospitals, 1 private not-for-profit research institute, and 1 community hospital. All the patients were interviewed independently of the usual preoperative psychosocial evaluation process. The patients were explicitly informed that the data would not be shared with the surgical team unless certain high-risk behaviors, such as suicidality, that could lead to adverse perioperative outcomes were reported.
Results: Most of the patients were women (82.9%) and white (nonwhite 7.6%, Hispanic 5.0%). The median age was 46.0 years, and the median body mass index was 44.9 kg/m(2). Of the 199 patients, 33.7% had >= 1 current Axis I disorder, and 68.8% had >= 1 lifetime Axis I disorder. Also, 38.7% had a lifetime history of a major depressive disorder, and 33.2% had a lifetime diagnosis of alcohol abuse or dependence. All these rates were much greater than the population-based prevalence rates obtained for this age group in the National Comorbidity Survey Replication Study. Also, 13.1% had a lifetime diagnosis and 10.1% had a current diagnosis of a binge eating disorder.
Conclusion: The current and lifetime rates of psychopathology are high in bariatric surgery candidates, and the lifetime rates of affective disorder and alcohol use disorders are particularly prominent. Finally, binge eating disorder is present in approximately 1 in 10 bariatric surgery candidates. (Surg Obes Relat Dis 2012;8:533-541.) (c) 2012 American Society for Metabolic and Bariatric Surgery. All rights reserved.
C1 [Mitchell, James E.; Wonderlich, Steve] Univ N Dakota, Sch Med & Hlth Sci, Neuropsychiat Res Inst, Fargo, ND 58102 USA.
[Selzer, Faith; Christian, Nicholas J.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA.
[Kalarchian, Melissa A.; Marcus, Marsha D.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA.
[Devlin, Michael J.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA.
[Strain, Gladys W.] Cornell Univ, Weill Cornell Sch Med, New York, NY 10021 USA.
[Elder, Katherine A.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Yanovski, Susan Z.] NIDDKD, NIH, Bethesda, MD 20892 USA.
RP Mitchell, JE (reprint author), Univ N Dakota, Sch Med & Hlth Sci, Neuropsychiat Res Inst, 120 S 8th St, Fargo, ND 58102 USA.
EM mitchell@medicine.nodak.edu
OI Kalarchian, Melissa/0000-0003-2099-9299
FU National Institute of Diabetes and Digestive and Kidney Diseases
[DSS-U01DK066557]; Columbia University [U01-DK66667]; Cornell University
Medical Center [ULI1-RR024996, UL1-RR0241531]; Neuropsychiatric Research
Institute [U01 -DK66471]; University of Pittsburgh Medical Center
[U01-DK66585]
FX This clinical study was a cooperative agreement funded by the National
Institute of Diabetes and Digestive and Kidney Diseases (grant
DSS-U01DK066557), Columbia University (grant U01-DK66667 [in
collaboration with Cornell University Medical Center, grant
ULI1-RR024996]), Neuropsychiatric Research Institute (grant U01
-DK66471), and University of Pittsburgh Medical Center (grant
U01-DK66585 [in collaboration with Cornell University Medical Center,
grant UL1-RR0241531]).
NR 47
TC 63
Z9 64
U1 2
U2 18
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1550-7289
J9 SURG OBES RELAT DIS
JI Surg. Obes. Relat. Dis.
PD SEP-OCT
PY 2012
VL 8
IS 5
BP 533
EP 541
DI 10.1016/j.soard.2012.07.001
PG 9
WC Surgery
SC Surgery
GA 018VQ
UT WOS:000309695100006
PM 22920965
ER
PT J
AU Blackstone, R
Bunt, JC
Cortes, MC
Sugerman, HJ
AF Blackstone, Robin
Bunt, Joy C.
Cortes, Melisa Celaya
Sugerman, Harvey J.
TI Type 2 diabetes after gastric bypass: remission in five models using
HbA1c, fasting blood glucose, and medication status
SO SURGERY FOR OBESITY AND RELATED DISEASES
LA English
DT Article
DE Bariatric surgery; Diabetes mellitus; Type 2 diabetes mellitus;
Roux-en-Y gastric bypass; Fasting blood glucose; Insulin; Hemoglobin A1c
ID LONG-TERM MORTALITY; ROUX-EN-Y; MORBIDLY OBESE-PATIENTS; BARIATRIC
SURGERY; WEIGHT-LOSS; FOLLOW-UP; GASTROINTESTINAL SURGERY;
CLINICAL-PRACTICE; US POPULATION; LIFE-STYLE
AB Background: The remission rates of type 2 diabetes mellitus (T2DM) after Roux-en-Y gastric bypass (RYGB) vary according to the glycosylated hemoglobin A1c (HbA1c), fasting blood glucose (FG), and medication status. Our objectives were to describe remission using the American Diabetes Association standards for defining normoglycemia and to identify the factors related to the preoperative severity of T2DM that predict remission to normoglycemia, independent of weight loss, after RYGB. The setting was an urban not-for-profit community hospital.
Methods: We performed a retrospective analysis of prospectively collected data from a cohort of 2275 patients who qualified for bariatric surgery (2001-2008). Five different models for defining remission (no diabetes medication and a FG < 100 mg/dL; no diabetes medication and HbA1c < 6.0; no diabetes medication and HbA1c < 5.7%; no diabetes medication, FG < 100 mg/dL, and HbA1c < 6.0%; and no diabetes medication, FG < 100 mg/dL, and HbAlc < 5.7%) were compared in 505 obese patients with T2DM 14 months after RYGB. The secondary aims were to determine the effects of preoperative insulin therapy and the duration of known T2DM on remission.
Results: Of the 505 patients, 43.2% achieved remission using the most stringent criteria (no diabetes medication, HbA1c < 5.7%, and FG < 100 mg/dL) compared with 59.4% using the most liberal definition (no diabetes medication and FG < 100 mg/dL; P < .001). The remission rates were greater for patients not taking insulin preoperatively (53.8% versus 13.5%, P < .001) and for patients with a more recent preoperative T2DM diagnosis (8.9 versus 3.7 yr, P < .001).
Conclusion: Remission, defined at a threshold less than what would be expected to result in microvascular damage, was achieved in 43.2% of diabetic patients by 14 months after RYGB. A more recent diagnosis of T2DM and the absence of preoperative insulin therapy were significant predictors, regardless of how remission was defined, independent of the percentage of excess weight loss. (Surg Obes Relat Dis 2012;8:548-555.) (c) 2012 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.
C1 [Blackstone, Robin; Cortes, Melisa Celaya] Scottsdale Healthcare Bariatr Ctr, Scottsdale, AZ 85258 USA.
[Blackstone, Robin] Univ Arizona, Coll Med, Dept Surg, Phoenix, AZ USA.
[Bunt, Joy C.] NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, Dept Hlth & Human Serv, Phoenix, AZ USA.
[Cortes, Melisa Celaya] Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Div Epidemiol & Biostat, Tucson, AZ USA.
[Sugerman, Harvey J.] Virginia Commonwealth Univ, Dept Surg, Richmond, VA USA.
RP Blackstone, R (reprint author), Scottsdale Healthcare Bariatr Ctr, 10210 N 92nd St,Suite 101, Scottsdale, AZ 85258 USA.
EM blackstonemd@mac.com
FU Intramural Research Program of the National Institutes of Health;
National Institute of Diabetes and Digestive and Kidney Diseases
FX Supported in part (contribution of J.C.B.) by the Intramural Research
Program of the National Institutes of Health and National Institute of
Diabetes and Digestive and Kidney Diseases.
NR 47
TC 39
Z9 42
U1 2
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1550-7289
J9 SURG OBES RELAT DIS
JI Surg. Obes. Relat. Dis.
PD SEP-OCT
PY 2012
VL 8
IS 5
BP 548
EP 555
DI 10.1016/j.soard.2012.05.005
PG 8
WC Surgery
SC Surgery
GA 018VQ
UT WOS:000309695100008
PM 22721581
ER
PT J
AU Shinohara, RT
Goldsmith, J
Mateen, FJ
Crainiceanu, C
Reich, DS
AF Shinohara, R. T.
Goldsmith, J.
Mateen, F. J.
Crainiceanu, C.
Reich, D. S.
TI Predicting Breakdown of the Blood-Brain Barrier in Multiple Sclerosis
without Contrast Agents
SO AMERICAN JOURNAL OF NEURORADIOLOGY
LA English
DT Article
ID ATTENUATED INVERSION-RECOVERY; NEPHROGENIC SYSTEMIC FIBROSIS;
GADOLINIUM; FREQUENCY; SEVERITY; LESIONS
AB BACKGROUND AND PURPOSE: Disruption of the BBB in MS is associated with the development of new lesions and clinical relapses and signifies the presence of active inflammation. It is most commonly detected as enhancement on MR imaging performed with contrast agents that are costly and occasionally toxic. We investigated whether the BBB status in white matter lesions may be indirectly ascertained via examination of features on T1- and T2-weighted images obtained before the injection of a contrast agent.
MATERIALS AND METHODS: We considered 93 brain MR imaging studies on 16 patients that included T1-, T2-, and T2-weighted FLAIR images and predicted voxel wise enhancement after intravenous injection of a gadolinium chelate. We then used these voxel-level predictions to determine the presence or absence of abnormal enhancement anywhere in the brain.
RESULTS: On a voxel-by-voxel basis, enhancement can be predicted by using contrast-free measures with an AUC of 0.83 (95% CI, 0.80-0.87). At the whole-brain level, enhancement can be predicted with an AUC of 0.72 (95% CI, 0.62-0.82).
CONCLUSIONS: In many cases, breakdown of the BBB in acute MS lesions may be inferred without the need to inject an MR imaging contrast agent. The inference relies on intrinsic properties of tissue damage in acute lesions. Although contrast studies are more accurate, they may sometimes be unnecessary.
C1 [Shinohara, R. T.; Goldsmith, J.; Crainiceanu, C.; Reich, D. S.] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA.
[Mateen, F. J.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA.
[Shinohara, R. T.; Reich, D. S.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA.
RP Shinohara, RT (reprint author), Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA.
EM taki.shinohara@gmail.com
RI Reich, Daniel/E-5701-2010
OI Reich, Daniel/0000-0002-2628-4334
FU Intramural Research Program of NINDS; NINDS [R01NS060910]; Epidemiology
and Biostatistics of Aging Training grant [T32 A0000247]; National
Institutes of Health, National Institute of Environmental Health
Sciences [2T32Es012871]
FX This work was supported by the Intramural Research Program of NINDS and
by NINDS R01NS060910 (R.T.S., J.G., C.C.). R.T.S. is supported by
Epidemiology and Biostatistics of Aging Training grant T32 A0000247.
A.J.G. is supported by Training Grant 2T32Es012871, from the National
Institutes of Health, National Institute of Environmental Health
Sciences.; Jeff Goldsmith-UNRELATED: Grants/Grants Pending: NINDS.
Ciprian Crainiceanu-UNRELATED: Consultancy: Merck, On-X, Comments: work
on sleep electroencephalography, unrelated to this article; work on an
adaptive clinical trial on mitral valve surgery.
NR 15
TC 6
Z9 7
U1 0
U2 0
PU AMER SOC NEURORADIOLOGY
PI OAK BROOK
PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA
SN 0195-6108
J9 AM J NEURORADIOL
JI Am. J. Neuroradiol.
PD SEP
PY 2012
VL 33
IS 8
BP 1586
EP 1590
DI 10.3174/ajnr.A2997
PG 5
WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 016AN
UT WOS:000309489800029
PM 22442041
ER
PT J
AU Houghton, LC
Booth, M
Hampshire, KR
Ziegler, RG
Katki, HA
Troisi, R
Hoover, RN
Chowdhury, OA
Bentley, GR
AF Houghton, Lauren C.
Booth, Mark
Hampshire, Kate R.
Ziegler, Regina G.
Katki, Hormuzd A.
Troisi, Rebecca
Hoover, Robert N.
Chowdhury, Osul A.
Bentley, Gillian R.
TI Should we include adrenarche in pubertal assessments?
SO ANNALS OF HUMAN BIOLOGY
LA English
DT Meeting Abstract
C1 [Houghton, Lauren C.; Ziegler, Regina G.; Katki, Hormuzd A.; Troisi, Rebecca; Hoover, Robert N.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Houghton, Lauren C.; Booth, Mark; Hampshire, Kate R.; Bentley, Gillian R.] Univ Durham, Durham DH1 3HP, England.
RI Booth, Mark/D-2266-2011; Katki, Hormuzd/B-4003-2015
OI Booth, Mark/0000-0002-5507-888X;
NR 0
TC 0
Z9 0
U1 0
U2 3
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0301-4460
J9 ANN HUM BIOL
JI Ann. Hum. Biol.
PD SEP-OCT
PY 2012
VL 39
IS 5
BP 449
EP 449
PG 1
WC Anthropology; Biology; Public, Environmental & Occupational Health
SC Anthropology; Life Sciences & Biomedicine - Other Topics; Public,
Environmental & Occupational Health
GA 022CS
UT WOS:000309933300016
ER
PT J
AU Zhang, W
Gao, JH
Yan, ZF
Liu, Z
Huang, XY
Sun, L
Yu, SY
Cao, CJ
Zuo, LJ
Hong, JS
Wang, YJ
Wang, XM
AF Zhang, W.
Gao, J. -H.
Yan, Z. -F.
Liu, Z.
Huang, X. -Y.
Sun, L.
Yu, S. -Y.
Cao, C. -J.
Zuo, L. -J.
Hong, J. -S.
Wang, Y. -J.
Wang, X. -M.
TI Minimally toxic dose of lipopolysaccharide and alpha-synuclein elicited
synergistic dopaminergic neurodegeneration: role and mechanisms of
microglial NOX2
SO EUROPEAN JOURNAL OF NEUROLOGY
LA English
DT Meeting Abstract
CT 16th Congress of the European-Federation-of-Neurological-Societies
(EFNS)
CY SEP 08-11, 2012
CL Stockholm, SWEDEN
SP European Federat Neurol Soc (EFNS)
C1 [Zhang, W.; Gao, J. -H.; Yan, Z. -F.; Liu, Z.; Huang, X. -Y.; Sun, L.; Yu, S. -Y.; Cao, C. -J.; Zuo, L. -J.; Wang, Y. -J.] Capital Med Univ, Beijing Tiantan Hosp, Beijing, Peoples R China.
[Hong, J. -S.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
[Wang, X. -M.] Capital Med Univ, Beijing, Peoples R China.
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 1351-5101
J9 EUR J NEUROL
JI Eur. J. Neurol.
PD SEP
PY 2012
VL 19
SU 1
SI SI
BP 57
EP 57
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 014FD
UT WOS:000309359700111
ER
PT J
AU Calvo, A
Restagno, G
Brunetti, M
Ossola, I
Majounie, E
Renton, AE
Canosa, A
Manera, U
Bersano, E
Moglia, C
Mora, G
Traynor, BJ
Chio, A
AF Calvo, A.
Restagno, G.
Brunetti, M.
Ossola, I.
Majounie, E.
Renton, A. E.
Canosa, A.
Manera, U.
Bersano, E.
Moglia, C.
Mora, G.
Traynor, B. J.
Chio, A.
TI UNC13A influences survival in an Italian population-based series
SO EUROPEAN JOURNAL OF NEUROLOGY
LA English
DT Meeting Abstract
CT 16th Congress of the European-Federation-of-Neurological-Societies
(EFNS)
CY SEP 08-11, 2012
CL Stockholm, SWEDEN
SP European Federat Neurol Soc (EFNS)
C1 [Calvo, A.; Canosa, A.; Manera, U.; Bersano, E.; Moglia, C.; Chio, A.] Univ Turin, ALS Ctr, S Giovanni Battista Hosp, Turin, Italy.
[Restagno, G.; Brunetti, M.; Ossola, I.] ASO OIRMS Anna, Mol Genet Unit, Turin, Italy.
[Majounie, E.] NIA, Neuromuscular Dis Res Unit, Bethesda, MD 20892 USA.
[Renton, A. E.; Traynor, B. J.] NIA, Mol Genet Unit, Neurogenet Lab, Bethesda, MD 20892 USA.
[Mora, G.] Salvatore Maugeri Fdn, IRCCS, ALS Ctr, Milan, Italy.
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 1351-5101
J9 EUR J NEUROL
JI Eur. J. Neurol.
PD SEP
PY 2012
VL 19
SU 1
SI SI
BP 262
EP 262
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 014FD
UT WOS:000309359701126
ER
PT J
AU Zhuang, Z
Yang, C
Lonser, RR
AF Zhuang, Z.
Yang, C.
Lonser, R. R.
TI Dissecting the molecular signalling pathways critical for astrocyte
activation and astrocytoma pathogenesis
SO EUROPEAN JOURNAL OF NEUROLOGY
LA English
DT Meeting Abstract
CT 16th Congress of the European-Federation-of-Neurological-Societies
(EFNS)
CY SEP 08-11, 2012
CL Stockholm, SWEDEN
SP European Federat Neurol Soc (EFNS)
C1 [Zhuang, Z.; Yang, C.; Lonser, R. R.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1351-5101
J9 EUR J NEUROL
JI Eur. J. Neurol.
PD SEP
PY 2012
VL 19
SU 1
SI SI
BP 762
EP 762
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 014FD
UT WOS:000309359705139
ER
PT J
AU Sallo, FB
Peto, T
Egan, C
Wolf-Schnurrbusch, UEK
Clemons, TE
Gillies, MC
Pauleikhoff, D
Rubin, GS
Chew, EY
Bird, AC
AF Sallo, Ferenc B.
Peto, Tunde
Egan, Catherine
Wolf-Schnurrbusch, Ute E. K.
Clemons, Traci E.
Gillies, Mark C.
Pauleikhoff, Daniel
Rubin, Gary S.
Chew, Emily Y.
Bird, Alan C.
CA MacTel Study Grp
TI "En face" OCT Imaging of the IS/OS Junction Line in Type 2 Idiopathic
Macular Telangiectasia
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; JUXTAFOVEOLAR RETINAL TELANGIECTASIS;
HIGH-SPEED; RETINITIS-PIGMENTOSA; HIGH-RESOLUTION; MICROPERIMETRY;
DEGENERATION; TOPOGRAPHY; IMAGES; ABNORMALITIES
AB PURPOSE. We investigated abnormalities of the photoreceptor inner/outer segment (IS/OS) junction layer viewed "en face" and their functional correlates in type 2 idiopathic macular telangiectasia (type 2 MacTel).
METHODS. Segmentation and "en face" imaging of the IS/OS lines in spectral domain optical coherence tomographic (SD-OCT) volumes were performed manually. Mesopic retinal sensitivity thresholds were determined using a Nidek MP1 microperimeter. "En face'' SD-OCT images and microperimetric data were superimposed over images of the fundus. Retinal structure and characteristics of type 2 MacTel were analyzed, and associations of structural changes with function were investigated.
RESULTS. We examined 49 eyes of 28 patients (mean age 62.6 +/- 9.4 years). Total IS/OS break area ranged from 0.04 to 2.23 mm(2) (mean 0.63 mm(2), SD 0.53 mm(2)) and 0.03 to 1.49 mm(2) (mean 0.49 mm(2), SD 0.42 mm(2)) in right and left eyes, respectively. A correlation between fellow eyes was present (Spearman correlation rho = 0.770, P < 0.01). An assessment of the repeatability of IS/OS lesion area measurements (n = 19 eyes) revealed an intra-class correlation coefficient of 0.99 (95% confidence interval [CI] of 0.975-0.996). Retinal areas corresponding to an IS/OS break showed a mean retinal sensitivity of 8.3 +/- 5.8 and 8.7 +/- 5.7 decibels (dB) in right and left eyes, respectively. Mean sensitivity over retinal areas outside the lesion was significantly higher, 17.0 +/- 3.3 and 16.7 +/- 3.6 dB in right and left eyes, respectively (paired t-test, P < 0.01). Mean aggregate retinal sensitivity loss was 33.5 +/- 30.4 dB (n = 40), correlating well with IS/OS lesion area (Pearson correlation coefficient = 0.848, P < 0.01).
CONCLUSIONS. "En face" OCT imaging of the IS/OS junction layer provides a functionally relevant method for assessing disease severity in type 2 MacTel. (Invest Ophthalmol Vis Sci. 2012; 53: 6145-6152) DOI: 10.1167/iovs.12-10580
C1 [Sallo, Ferenc B.] Moorfields Eye Hosp NHS Fdn Trust, Dept Res & Dev, Reading Ctr, Moorfields Eye Hosp, London EC1V 2PD, England.
[Bird, Alan C.] Moorfields Eye Hosp, Inherited Eye Dis, London, England.
[Sallo, Ferenc B.; Peto, Tunde; Rubin, Gary S.] UCL Inst Ophthalmol, London, England.
[Sallo, Ferenc B.; Wolf-Schnurrbusch, Ute E. K.] Univ Hosp Bern, Bern Photog Reading Ctr, Dept Ophthalmol, CH-3010 Bern, Switzerland.
[Peto, Tunde] Moorfields Eye Hosp NHS Fdn Trust, NIHR Biomed Res Ctr Ophthalmol, London EC1V 2PD, England.
[Clemons, Traci E.] EMMES Corp, Rockville, MD USA.
[Gillies, Mark C.] Univ Sydney, Save Sight Inst, Sydney, NSW 2006, Australia.
[Pauleikhoff, Daniel] St Franziskus Hosp, Munster, Germany.
[Chew, Emily Y.] NEI, NIH, Bethesda, MD 20892 USA.
RP Sallo, FB (reprint author), Moorfields Eye Hosp NHS Fdn Trust, Dept Res & Dev, Reading Ctr, Moorfields Eye Hosp, 162 City Rd, London EC1V 2PD, England.
EM Ferenc.Sallo@moorfields.nhs.uk
RI gillies, mark/B-3242-2012; Wolf, Sebastian/B-8782-2008; Sahel,
Jose-Alain/F-3172-2017
OI Wolf, Sebastian/0000-0002-7467-7028;
FU Lowy Medical Research Institute (LMRI); NIHR
FX Supported by the Lowy Medical Research Institute (LMRI) and the NIHR.
NR 50
TC 28
Z9 28
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 2012
VL 53
IS 10
BP 6145
EP 6152
DI 10.1167/iovs.12-10580
PG 8
WC Ophthalmology
SC Ophthalmology
GA 016NQ
UT WOS:000309526200022
PM 22899757
ER
PT J
AU Pilotto, A
Panza, F
Sancarlo, D
Paroni, G
Maggi, S
Ferrucci, L
AF Pilotto, Alberto
Panza, Francesco
Sancarlo, Daniele
Paroni, Giulia
Maggi, Stefania
Ferrucci, Luigi
TI Usefulness of the multidimensional prognostic index (MPI) in the
management of older patients with chronic kidney disease
SO JOURNAL OF NEPHROLOGY
LA English
DT Article
DE Aging; All-cause mortality; Chronic kidney disease; Comprehensive
geriatric assessment; Elderly; Multidimensional prognostic index
ID COMPREHENSIVE GERIATRIC ASSESSMENT; GLOMERULAR-FILTRATION-RATE;
LONG-TERM MORTALITY; ELDERLY-PATIENTS; 1-YEAR MORTALITY; ALL-CAUSE;
VALIDATION; ADULTS; HOSPITALIZATION; PREVALENCE
AB In older patients, given the central role of prognosis in clinical decision-making, there is an urgent need to develop accurate, validated, and rigorously tested prognostic indices. Current data suggest that in older patients not only physical but also psychological, cognitive, functional, nutritional, biological, and social factors may contribute to the increased risk of negative outcomes including institutionalization, hospitalization, and mortality. Recently, a Multidimensional Prognostic Index (MPI), derived from a standardized comprehensive geriatric assessment that included information from eight domains, i.e. basal and instrumental activities of daily living, cognitive and nutritional status, the risk for pressure sores, comorbidities, drug use, and co-habitation status was effective in predicting short- and long-term all-cause mortality risk in hospitalized patients with various acute and chronic conditions, including chronic kidney disease (CKD). In a consecutive cohort of patients with CKD the MPI accuracy in predicting mortality was significantly higher than the accuracy of the estimated glomerular filtration rate (eGFR). More recently, findings from hospital-based cohorts suggest that adding MPI information to the eGFR markedly improved the prediction of two-year all-cause mortality in older patients with CKD. While further studies are needed to assess the potential usefulness of this prognostic tool in clinical practice, a multidimensional assessment for all-cause mortality risk prediction should be considered in older patients with CKD. These findings support the concept that considering multidimensional aggregate information is very important for predicting short- and long-term all-cause mortality in older subjects with CKD, and that it may be important for the identification of more suitable management of these patients.
C1 [Pilotto, Alberto] S Antonio Hosp, Geriatr Unit, Azienda ULSS Padova 16, I-35127 Padua, Italy.
[Pilotto, Alberto; Panza, Francesco; Sancarlo, Daniele; Paroni, Giulia] IRCCS Casa Sollievo Sofferenza, Dept Med Sci, Gerontol Geriatr Res Lab, Foggia, Italy.
[Maggi, Stefania] CNR, Aging Sect, Padua, Italy.
[Ferrucci, Luigi] NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21224 USA.
RP Pilotto, A (reprint author), S Antonio Hosp, Geriatr Unit, Azienda ULSS Padova 16, Via Facciolati 71, I-35127 Padua, Italy.
EM alberto.pilotto@sanita.padova.it
RI Sancarlo, Daniele/C-1056-2017; Paroni, Giulia/C-3768-2017;
OI Sancarlo, Daniele/0000-0001-9541-6364; Paroni,
Giulia/0000-0003-0240-8475; Panza, Francesco/0000-0002-7220-0656
FU Ministero della Salute, IRCCS Research Program; Intramural Research
Program of the National Institute of Aging, Baltimore, USA
FX This work was supported by the Ministero della Salute, IRCCS Research
Program 2009-2011, Line 2: Malattie complesse, and by the Intramural
Research Program of the National Institute of Aging, Baltimore, USA.
NR 44
TC 7
Z9 7
U1 2
U2 6
PU WICHTIG EDITORE
PI MILAN
PA 72/74 VIA FRIULI, 20135 MILAN, ITALY
SN 1121-8428
J9 J NEPHROL
JI J. Nephrol.
PD SEP-OCT
PY 2012
VL 25
SU 19
SI SI
BP S79
EP S84
DI 10.5301/jn.5000162
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA 015IV
UT WOS:000309440500014
PM 22641578
ER
PT J
AU Thoolen, B
ten Kate, FJW
van Diest, PJ
Malarkey, DE
Elmore, SA
Maronpot, RR
AF Thoolen, Bob
ten Kate, Fiebo J. W.
van Diest, Paul J.
Malarkey, David E.
Elmore, Susan A.
Maronpot, Robert R.
TI Comparative Histomorphological Review of Rat and Human Hepatocellular
Proliferative Lesions
SO JOURNAL OF TOXICOLOGIC PATHOLOGY
LA English
DT Review
DE liver; hepatocellular carcinoma; hepatocellular adenoma; large cell
change; small cell change; foci of cellular alteration
ID LIVER-CELL DYSPLASIA; FOCAL NODULAR HYPERPLASIA; CHRONIC
VIRAL-HEPATITIS; EMBRYONAL TURKEY LIVER; ALTERED HEPATOCYTES;
MALIGNANT-TRANSFORMATION; SUBTYPE CLASSIFICATION; PROGENITOR CELLS;
PREDICTIVE-VALUE; CARCINOMA
AB In this comparative review, histomorphological features of common nonneoplastic and neoplastic hepatocyte lesions of rats and humans are examined using ME-stained slides. The morphological similarities and differences of both neoplastic (hepatocellular carcinoma and hepatocellular adenoma) and presumptive preneoplastic lesions (large and small cell change in humans and foci of cellular alteration in rats) are presented and discussed. There are major similarities in the diagnostic features, growth patterns and behavior of both rat and human hepatocellular proliferative lesions and in the process of hepatocarcinogenesis. Further study of presumptive preneoplastic lesions in humans and rats should help to further define their role in progression to hepatocellular neoplasia in both species. (DOI: 10.1293/tox.25.189; J Toxicol Pathol 2012; 25: 189-199)
C1 [Thoolen, Bob] Global Pathol Support, NL-2596 BA The Hague, Netherlands.
[Thoolen, Bob; ten Kate, Fiebo J. W.; van Diest, Paul J.] Univ Med Ctr Utrecht, NL-3508 GA Utrecht, Netherlands.
[Malarkey, David E.; Elmore, Susan A.] NIEHS, Natl Toxicol Program, Cellular & Mol Pathol Branch, Res Triangle Pk, NC 27709 USA.
[Maronpot, Robert R.] Maronpot Consulting LLC, Raleigh, NC 27607 USA.
RP Thoolen, B (reprint author), Global Pathol Support, Benoordenhoutseweg 23, NL-2596 BA The Hague, Netherlands.
EM bob.thoolen@gpstox-path.com
FU Division of the National Toxicology Program of the NIH, National
Institute of Environmental Health Sciences
FX This research was supported [in part] by the Division of the National
Toxicology Program of the NIH, National Institute of Environmental
Health Sciences. This article may be the work product of an employee or
group of employees of the National Institute of Environmental Health
Sciences (NIEHS), National Institutes of Health (NIH), however, the
statements, opinions or conclusions contained therein do not necessarily
represent the statements, opinions or conclusions of NIEHS, NIH or the
United States government.
NR 95
TC 5
Z9 5
U1 2
U2 5
PU JAPANESE SOC TOXICOLOGIC PATHOLOGY
PI TOKYO
PA DEPT ACAD SOC, MEDICAL TRIBUNE INC, ITALIAN CULTURAL INST BLDG 8F
2-1-30, KUDAN MINAMI, CHIYODA, TOKYO, 102-0074, JAPAN
SN 0914-9198
J9 J TOXICOL PATHOL
JI J. Toxicol. Pathol.
PD FAL
PY 2012
VL 25
IS 3
BP 189
EP 199
DI 10.1293/tox.25.189
PG 11
WC Pathology; Toxicology
SC Pathology; Toxicology
GA 017CH
UT WOS:000309567200001
PM 22988337
ER
PT J
AU Camp, KM
Lloyd-Puryear, MA
Huntington, KL
AF Camp, Kathryn M.
Lloyd-Puryear, Michele A.
Huntington, Kathleen L.
TI Nutritional treatment for inborn errors of metabolism: Indications,
regulations, and availability of medical foods and dietary supplements
using phenylketonuria as an example
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Review
DE Inborn errors of metabolism; Inherited metabolic disorders;
Phenylketonuria; PKU; Medical food; Treatment
AB Medical foods and dietary supplements are used to treat rare inborn errors of metabolism (IEM) identified through state-based universal newborn screening. These products are regulated under Food and Drug Administration (FDA) food and dietary supplement statutes. The lack of harmony in terminology used to refer to medical foods and dietary supplements and the misuse of words that imply that FDA regulates these products as drugs have led to confusion. These products are expensive and, although they are used for medical treatment of IEM, third-party payer coverage of these products is inconsistent across the United States. Clinicians and families report termination of coverage in late adolescence, failure to cover treatment during pregnancy, coverage for select conditions only, or no coverage. We describe the indications for specific nutritional treatment products for IEM and their regulation, availability, and categorization. We conclude with a discussion of the problems that have contributed to the paradox of identifying individuals with IEM through newborn screening but not guaranteeing that they receive optimal treatment. Throughout the paper, we use the nutritional treatment of phenylketonuria as an example of IEM treatment. (c) 2012 Elsevier Inc. All rights reserved.
C1 [Camp, Kathryn M.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
[Lloyd-Puryear, Michele A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
[Huntington, Kathleen L.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA.
RP Camp, KM (reprint author), 6100 Execut Blvd, Rockville, MD 20892 USA.
EM campkm@od.nih.gov; lloydpuryearma@mail.nih.gov; huntingt@ohsu.edu
FU Intramural NIH HHS [Z99 OD999999]
NR 21
TC 25
Z9 25
U1 1
U2 32
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 2012
VL 107
IS 1-2
SI SI
BP 3
EP 9
DI 10.1016/j.ymgme.2012.07.005
PG 7
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 014KI
UT WOS:000309374200001
PM 22854513
ER
PT J
AU Haddad, MR
Macri, CJ
Holmes, CS
Goldstein, DS
Jacobson, BE
Centeno, JA
Popek, EJ
Gahl, WA
Kaler, SG
AF Haddad, Marie Reine
Macri, Charles J.
Holmes, Courtney S.
Goldstein, David S.
Jacobson, Beryl E.
Centeno, Jose A.
Popek, Edwina J.
Gahl, Wiliam A.
Kaler, Stephen G.
TI In utero copper treatment for Menkes disease associated with a severe
ATP7A mutation
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE Copper; ATP7A; Fetal therapy; Menkes disease; mRNA splicing
ID PEDIATRIC REFERENCE INTERVALS; DEVELOPING BRAIN; THERAPY; TRANSPORT;
PLASMA; VARIABILITY; EXPRESSION; DIAGNOSIS; PROTEINS
AB Menkes disease is a lethal X-linked recessive neurodegenerative disorder of copper transport caused by mutations in ATP7A, which encodes a copper-transporting ATPase. Early postnatal treatment with copper injections often improves clinical outcomes in affected infants. While Menkes disease newborns appear normal neurologically, analyses of fetal tissues including placenta indicate abnormal copper distribution and suggest a prenatal onset of the metal transport defect In an affected fetus whose parents found termination unacceptable and who understood the associated risks, we began in utero copper histidine treatment at 31.5 weeks gestational age. Copper histidine (900 mu g per dose) was administered directly to the fetus by intramuscular injection (fetal quadriceps or gluteus) under ultrasound guidance. Percutaneous umbilical blood sampling enabled serial measurement of fetal copper and ceruloplasmin levels that were used to guide therapy over a four-week period. Fetal copper levels rose from 17 mu g/dL prior to treatment to 45 mu g/dL, and ceruloplasmin levels from 39 mg/L to 122 mg/L After pulmonary maturity was confirmed biochemically, the baby was delivered at 35.5 weeks and daily copper histidine therapy (250 mu g Sc bid.) was begun. Despite this very early intervention with copper, the infant showed hypotonia, developmental delay, and electroencephalographic abnormalities and died of respiratory failure at 5.5 months of age. The patient's ATP7A mutation (Q724H), which severely disrupted mRNA splicing, resulted in complete absence of ATP7A protein on Westem blots. These investigations suggest that prenatally initiated copper replacement is inadequate to correct Menkes disease caused by severe loss-of-function mutations, and that postnatal ATP7A gene addition represents a rational approach in such circumstances. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Haddad, Marie Reine; Kaler, Stephen G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Human Copper Metab, Program Mol Med, NIH, Bethesda, MD 20892 USA.
[Macri, Charles J.] George Washington Univ, Sch Med, Dept Obstet & Gynecol, Div Maternal Fetal Med, Washington, DC USA.
[Holmes, Courtney S.; Goldstein, David S.] NINDS, Sect Neurocardiol, NIH, Bethesda, MD 20892 USA.
[Jacobson, Beryl E.] BC Childrens Hosp, Dept Clin Biochem, Vancouver, BC, Canada.
[Centeno, Jose A.] Joint Pathol Ctr, Div Biophys Toxicol, Silver Spring, MD USA.
[Popek, Edwina J.] Texas Childrens Hosp, Baylor Coll Med, Dept Pediat Pathol, Houston, TX 77030 USA.
[Gahl, Wiliam A.] NHGRI, Sect Human Biochem Genet, NIH, Bethesda, MD 20892 USA.
RP Kaler, SG (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Human Copper Metab, Program Mol Med, NIH, Bldg 10,Room 10N313,10 Ctr Dr,MSC 1853, Bethesda, MD 20892 USA.
EM kalers@mail.nih.gov
FU Intramural NIH HHS [ZIA HD008768-08]
NR 34
TC 9
Z9 10
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 1096-7192
EI 1096-7206
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD SEP-OCT
PY 2012
VL 107
IS 1-2
SI SI
BP 222
EP 228
DI 10.1016/j.ymgme.2012.05.008
PG 7
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 014KI
UT WOS:000309374200030
PM 22695177
ER
PT J
AU Vanderver, A
Tonduti, D
Auerbach, S
Schmidt, JL
Parikh, S
Gowans, GC
Jackson, KE
Brock, PL
Patterson, M
Nehrebecky, M
Godfrey, R
Zein, WM
Gahl, W
Toro, C
AF Vanderver, Adeline
Tonduti, Davide
Auerbach, Sarah
Schmidt, Johanna L.
Parikh, Sumit
Gowans, Gordon C.
Jackson, Kelly E.
Brock, Pamela L.
Patterson, Marc
Nehrebecky, Michelle
Godfrey, Rena
Zein, Wadih M.
Gahl, William
Toro, Camilo
TI Neurotransmitter abnormalities and response to supplementation in SPG11
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE Spastic paraparesis; Dopa responsive dystonia; Neurotransmitter
disorder; SPG11
ID HEREDITARY SPASTIC PARAPLEGIA; THIN CORPUS-CALLOSUM; SPATACSIN
MUTATIONS; DEGENERATION; PARAPARESIS; SPECTRUM
AB Objective: To report the detection of secondary neurotransmitter abnormalities in a group of SPG11 patients and describe treatment with L-dopa/carbidopa and sapropterin.
Design: Case reports.
Setting: National Institutes of Health in the Undiagnosed Disease Program; Children's National Medical Center in the Myelin Disorders Bioregistry Program.
Patients: Four SPG11 patients with a clinical picture of progressive spastic paraparesis complicated by extrapyramidal symptoms and maculopathy.
Interventions: L-Dopa/carbidopa and sapropterin.
Results: 3/4 patients presented secondary neurotransmitter abnormalities; 4/4 partially responded to L-dopa as well as sapropterin.
Conclusions: In the SPG11 patient with extrapyramidal symptoms, a trial of L-dopa/carbidopa and sapropterin anti/or evaluation of cerebrospinal fluid neurotransmitters should be considered. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Vanderver, Adeline; Auerbach, Sarah; Schmidt, Johanna L.] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA.
[Tonduti, Davide] Univ Pavia, IRCCS C Mondino Natl Inst, Child Neurol & Psychiat Unit, Neurol Fdn, I-27100 Pavia, Italy.
[Parikh, Sumit] Cleveland Clin, Neurol Inst, Ctr Pediat Neurol & Neurosurg, Cleveland, OH 44106 USA.
[Gowans, Gordon C.; Jackson, Kelly E.; Brock, Pamela L.] Univ Louisville, Weisskopf Child Evaluat Ctr, Louisville, KY 40292 USA.
[Patterson, Marc] Mayo Clin Childrens Ctr, Dept Neurol, Rochester, MN USA.
[Patterson, Marc] Mayo Clin Childrens Ctr, Dept Pediat, Rochester, MN USA.
[Patterson, Marc] Mayo Clin Childrens Ctr, Dept Med Genet, Rochester, MN USA.
[Nehrebecky, Michelle; Godfrey, Rena; Gahl, William; Toro, Camilo] NIH, NIH Undiagnosed Dis Program, Off Director, Bethesda, MD 20892 USA.
[Zein, Wadih M.] NEI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Gahl, William] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Vanderver, A (reprint author), Childrens Natl Med Ctr, Ctr Genet Med Res CGMR, 111 Michigan Ave NW, Washington, DC 20010 USA.
EM avanderv@childrensnational.org
RI tonduti, davide/K-1673-2016;
OI tonduti, davide/0000-0001-9371-7454; Patterson, Marc/0000-0002-1116-126X
FU National Human Genome Research Institute, NIH
FX Patients 1, 2 and 3 were enrolled via the Myelin Disorders Bioregistry
Program and all patients were evaluated as part of the Undiagnosed
Disease Program at the National Institutes of Health (NIH). Thanks are
given to the administrative staff of the Undiagnosed Disease Program
(UDP) for their logistical efforts. Thanks are also given to referring
physicians and patients described in this report, in particular Dr.
Steven Vernino for his assistance on outpatient care in one case.
Interpretation of neurotransmitter abnormalities was assisted by Dr.
Philip Pearl at Children's National Medical Center. The contributions of
A.V. were supported by the intramural program at the National Human
Genome Research Institute, NIH. Assistance in description of mutation
status was provided by Khalida Liaquat, MS, CGC, Genetic Counselor at
Athena Diagnostics.
NR 18
TC 3
Z9 3
U1 1
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 2012
VL 107
IS 1-2
SI SI
BP 229
EP 233
DI 10.1016/j.ymgme.2012.05.020
PG 5
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 014KI
UT WOS:000309374200031
PM 22749184
ER
PT J
AU Wuchty, S
Arjona, D
Bozdag, S
Bauer, PO
AF Wuchty, Stefan
Arjona, Dolores
Bozdag, Serdar
Bauer, Peter O.
TI Involvement of microRNA families in cancer
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID GENES; ONCOGENES; ONCOMIRS; TARGETS; NETWORK
AB Collecting representative sets of cancer microRNAs (miRs) from the literature we show that their corresponding families are enriched in sets of highly interacting miR families. Targeting cancer genes on a statistically significant level, such cancer miR families strongly intervene with signaling pathways that harbor numerous cancer genes. Clustering miR family-specific profiles of pathway intervention, we found that different miR families share similar interaction patterns. Resembling corresponding patterns of cancer miRs families, such interaction patterns may indicate a miR family's potential role in cancer. As we find that the number of targeted cancer genes is a naive proxy for a cancer miR family, we design a simple method to predict candidate miR families based on gene-specific interaction profiles. Assessing the impact of miR families to distinguish between (non-)cancer genes, we predict a set of 84 potential candidate families, including 75% of initially collected cancer miR families. Further confirming their relevance, predicted cancer miR families are significantly indicated in increasing, non-random numbers of tumor types.
C1 [Wuchty, Stefan] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
[Arjona, Dolores] GeneDX Inc, Gaithersburg, MD 20877 USA.
[Bozdag, Serdar; Bauer, Peter O.] NCI, Neurooncol Branch, NINDS, NIH, Bethesda, MD 20892 USA.
RP Wuchty, S (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM wuchtys@ncbi.nlm.nih.gov
FU The National Institutes of Health/Department of Health and Human Service
(DHHS) (Intramural Research program of the National Library of Medicine)
FX Funding for open access charge: The National Institutes of
Health/Department of Health and Human Service (DHHS) (Intramural
Research program of the National Library of Medicine).
NR 32
TC 8
Z9 9
U1 0
U2 3
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 2012
VL 40
IS 17
BP 8219
EP 8226
DI 10.1093/nar/gks627
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 015RS
UT WOS:000309464300013
PM 22743268
ER
PT J
AU Zeng, ZH
Sharma, A
Ju, LM
Murai, J
Umans, L
Vermeire, L
Pommier, Y
Takeda, S
Huylebroeck, D
Caldecott, KW
El-Khamisy, SF
AF Zeng, Zhihong
Sharma, Abhishek
Ju, Limei
Murai, Junko
Umans, Lieve
Vermeire, Liesbeth
Pommier, Yves
Takeda, Shunichi
Huylebroeck, Danny
Caldecott, Keith W.
El-Khamisy, Sherif F.
TI TDP2 promotes repair of topoisomerase I-mediated DNA damage in the
absence of TDP1
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID STRAND BREAK REPAIR; SPINOCEREBELLAR ATAXIA; PHOSPHODIESTERASE 1; AXONAL
NEUROPATHY; VERTEBRATE CELLS; ENZYME; PROTEIN; COMPLEXES; VANADATE;
MUTATION
AB The abortive activity of topoisomerases can result in clastogenic and/or lethal DNA damage in which the topoisomerase is covalently linked to the 3'- or 5'-terminus of a DNA strand break. This type of DNA damage is implicated in chromosome translocations and neurological disease and underlies the clinical efficacy of an important class of anticancer topoisomerase 'poisons'. Tyrosyl DNA phosphodiesterase-1 protects cells from abortive topoisomerase I (Top1) activity by hydrolyzing the 3'-phosphotyrosyl bond that links Top1 to a DNA strand break and is currently the only known human enzyme that displays this activity in cells. Recently, we identified a second tyrosyl DNA phosphodiesterase (TDP2; aka TTRAP/EAPII) that possesses weak 3'-tyrosyl DNA phosphodiesterase (3'-TDP) activity, in vitro. Herein, we have examined whether TDP2 contributes to the repair of Top1-mediated DNA breaks by deleting Tdp1 and Tdp2 separately and together in murine and avian cells. We show that while deletion of Tdp1 in wild-type DT40 cells and mouse embryonic fibroblasts decreases DNA strand break repair rates and cellular survival in response to Top1-induced DNA damage, deletion of Tdp2 does not. However, deletion of both Tdp1 and Tdp2 reduces rates of DNA strand break repair and cell survival below that observed in Tdp1(-/-) cells, suggesting that Tdp2 contributes to cellular 3'-TDP activity in the absence of Tdp1. Consistent with this idea, over-expression of human TDP2 in Tdp1(-/-)/Tdp2(-/-/-) DT40 cells increases DNA strand break repair rates and cell survival above that observed in Tdp1(-/-) DT40 cells, suggesting that Tdp2 over-expression can partially complement the defect imposed by loss of Tdp1. Finally, mice lacking both Tdp1 and Tdp2 exhibit greater sensitivity to Top1 poisons than do mice lacking Tdp1 alone, further suggesting that Tdp2 contributes to the repair of Top1-mediated DNA damage in the absence of Tdp1. In contrast, we failed to detect a contribution for Tdp1 to repair Top2-mediated damage. Together, our data suggest that Tdp1 and Tdp2 fulfil overlapping roles following Top1-induced DNA damage, but not following Top2-induced DNA damage, in vivo.
C1 [Zeng, Zhihong; Sharma, Abhishek; Ju, Limei; Caldecott, Keith W.; El-Khamisy, Sherif F.] Univ Sussex, Genome Damage & Stabil Ctr, Sch Life Sci, Brighton BN1 9RQ, E Sussex, England.
[Murai, Junko; Pommier, Yves] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Umans, Lieve; Vermeire, Liesbeth; Huylebroeck, Danny] Univ Leuven, Dept Dev & Regenerat, Lab Mol Biol Celgen, Louvain, Belgium.
[Takeda, Shunichi] Kyoto Univ, Dept Radiat Genet, Kyoto, Japan.
[El-Khamisy, Sherif F.] Ain Shams Univ, Dept Biochem, Fac Pharm, Cairo, Egypt.
RP El-Khamisy, SF (reprint author), Univ Sussex, Genome Damage & Stabil Ctr, Sch Life Sci, Sci Pk Rd, Brighton BN1 9RQ, E Sussex, England.
EM k.w.caldecott@sussex.ac.uk; smfame20@sussex.ac.uk
OI , Sherif/0000-0003-2721-7763; Huylebroeck, Danny/0000-0003-4862-1079
FU MRC [MR/J006750/1]; Wellcome trust [085284, 091043]; EC FP6 Integrated
Project EndoTrack and Interuniversity Attraction Pole [IUAP-P6/20];
VIB7; Wellcome Trust
FX Z.Z. and L.J. were funded by MRC grants to K.W.C. [MR/J006750/1]; A.S.
was funded by Wellcome trust grants to S.E.K. [085284 and 091043];
Generation of the Tdp2 (Ttrap)-/- mouse in the DH laboratory
was supported by the EC FP6 Integrated Project EndoTrack and
Interuniversity Attraction Pole IUAP-P6/20 and, in an early phase, VIB7
funding. Center for Cancer Research, the Intramural Program of the US
National Cancer Institute, NIH [to J.M. and Y.P.]. Funding for open
access charge: Wellcome Trust Fellowship (to S.E.K.).
NR 26
TC 34
Z9 36
U1 1
U2 19
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 2012
VL 40
IS 17
BP 8371
EP 8380
DI 10.1093/nar/gks622
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 015RS
UT WOS:000309464300026
PM 22740648
ER
PT J
AU Berquist, BR
Canugovi, C
Sykora, P
Wilson, DM
Bohr, VA
AF Berquist, Brian R.
Canugovi, Chandrika
Sykora, Peter
Wilson, David M., III
Bohr, Vilhelm A.
TI Human Cockayne syndrome B protein reciprocally communicates with
mitochondrial proteins and promotes transcriptional elongation
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID RNA-POLYMERASE-II; BASE EXCISION-REPAIR; CSB ERCC6 GENE; DNA-DAMAGE;
FACTOR-A; OXIDATIVE STRESS; COUPLING FACTOR; IN-VITRO; MUTATIONS;
ACCUMULATION
AB Cockayne syndrome (CS) is a rare human disorder characterized by pathologies of premature aging, neurological abnormalities, sensorineural hearing loss and cachectic dwarfism. With recent data identifying CS proteins as physical components of mitochondria, we sought to identify protein partners and roles for Cockayne syndrome group B (CSB) protein in this organelle. CSB was found to physically interact with and modulate the DNA-binding activity of the major mitochondrial nucleoid, DNA replication and transcription protein TFAM. Components of the mitochondrial transcription apparatus (mitochondrial RNA polymerase, transcription factor 2B and TFAM) all functionally interacted with CSB and stimulated its double-stranded DNA-dependent adenosine triphosphatase activity. Moreover, we found that patient-derived CSB-deficient cells exhibited a defect in efficient mitochondrial transcript production and that CSB specifically promoted elongation by the mitochondrial RNA polymerase in vitro. These observations provide strong evidence for the importance of CSB in maintaining mitochondrial function and argue that the pathologies associated with CS are in part, a direct result of the roles that CSB plays in mitochondria.
C1 [Berquist, Brian R.; Canugovi, Chandrika; Sykora, Peter; Wilson, David M., III; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM wilsonda@mail.nih.gov; vbohr@nih.gov
FU National Institutes of Health, National Institute on Aging; NIH
FX Intramural Research Program of the National Institutes of Health,
National Institute on Aging. Funding for open access charge: NIH.
NR 57
TC 25
Z9 25
U1 1
U2 10
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 2012
VL 40
IS 17
BP 8392
EP 8405
DI 10.1093/nar/gks565
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 015RS
UT WOS:000309464300028
PM 22743267
ER
PT J
AU Kanagaraj, R
Parasuraman, P
Mihaljevic, B
van Loon, B
Burdova, K
Konig, C
Furrer, A
Bohr, VA
Hubscher, U
Janscak, P
AF Kanagaraj, Radhakrishnan
Parasuraman, Prasanna
Mihaljevic, Boris
van Loon, Barbara
Burdova, Kamila
Koenig, Christiane
Furrer, Antonia
Bohr, Vilhelm A.
Huebscher, Ulrich
Janscak, Pavel
TI Involvement of Werner syndrome protein in MUTYH-mediated repair of
oxidative DNA damage
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID BASE EXCISION-REPAIR; POLYMERASE-LAMBDA; REPLICATION FORK; 8-OXO-GUANINE
REPAIR; FLAP ENDONUCLEASE-1; HELICASE ACTIVITY; HUMAN RECQ5-BETA; WRN;
CELLS; GLYCOSYLASE
AB Reactive oxygen species constantly generated as by-products of cellular metabolism readily attack genomic DNA creating mutagenic lesions such as 7,8-dihydro-8-oxo-guanine (8-oxo-G) that promote aging. 8-oxo-G:A mispairs arising during DNA replication are eliminated by base excision repair initiated by the MutY DNA glycosylase homologue (MUTYH). Here, by using formaldehyde crosslinking in mammalian cell extracts, we demonstrate that the WRN helicase/exonuclease defective in the premature aging disorder Werner syndrome (WS) is recruited to DNA duplex containing an 8-oxo-G:A mispair in a manner dependent on DNA polymerase lambda (Pol lambda) that catalyzes accurate DNA synthesis over 8-oxo-G. Similarly, by immunofluorescence, we show that Pol lambda is required for accumulation of WRN at sites of 8-oxo-G lesions in human cells. Moreover, we show that nuclear focus formation of WRN and Pol lambda induced by oxidative stress is dependent on ongoing DNA replication and on the presence of MUTYH. Cell viability assays reveal that depletion of MUTYH suppresses the hypersensitivity of cells lacking WRN and/or Pol lambda to oxidative stress. Biochemical studies demonstrate that WRN binds to the catalytic domain of Pol lambda and specifically stimulates DNA gap filling by Pol lambda over 8-oxo-G followed by strand displacement synthesis. Our results suggest that WRN promotes long-patch DNA repair synthesis by Pol lambda during MUTYH-initiated repair of 8-oxo-G:A mispairs.
C1 [Kanagaraj, Radhakrishnan; Mihaljevic, Boris; Koenig, Christiane; Janscak, Pavel] Univ Zurich, Inst Mol Canc Res, CH-8057 Zurich, Switzerland.
[Parasuraman, Prasanna; van Loon, Barbara; Furrer, Antonia; Huebscher, Ulrich] Univ Zurich, Inst Vet Biochem & Mol Biol, CH-8057 Zurich, Switzerland.
[Burdova, Kamila] Acad Sci Czech Republic, Inst Mol Genet, Prague 14300, Czech Republic.
[Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD USA.
RP Janscak, P (reprint author), Univ Zurich, Inst Mol Canc Res, Winterthurerstr 190, CH-8057 Zurich, Switzerland.
EM hubscher@vetbio.uzh.ch; pjanscak@imcr.uzh.ch
RI Janscak, Pavel/G-6189-2014; Radhakrishnan, Kanagaraj/O-3205-2016
FU Swiss National Science Foundation [31003A-129747/1, 3100-109312/2]; UBS
AG; Oncosuisse [KLS-02344-02-2009]; Stiftung zur Krebsbekampfung;
University of Zurich; National Institutes of Health Intramural Program
of the National Institute on Aging [Z01-AG000726-17]; Swiss National
Science Foundation
FX Swiss National Science Foundation [31003A-129747/1 to P.J.];
[3100-109312/2 to U.H., P.P. and B.V.L.]; UBS AG to P.J. and R.K.;
Oncosuisse [KLS-02344-02-2009 to P.J.]; Stiftung zur Krebsbekampfung (to
P.J.); University of Zurich (to U. H., B. V. L. and P.J.). National
Institutes of Health Intramural Program of the National Institute on
Aging [Z01-AG000726-17, in part]. Funding for open access charge: Swiss
National Science Foundation.
NR 45
TC 11
Z9 12
U1 3
U2 9
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 2012
VL 40
IS 17
BP 8449
EP 8459
DI 10.1093/nar/gks648
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 015RS
UT WOS:000309464300033
PM 22753033
ER
PT J
AU Takeda, Y
Jothi, R
Birault, V
Jetten, AM
AF Takeda, Yukimasa
Jothi, Raja
Birault, Veronique
Jetten, Anton M.
TI ROR gamma directly regulates the circadian expression of clock genes and
downstream targets in vivo
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID ORPHAN NUCLEAR RECEPTOR; REV-ERB-ALPHA; HISTONE ACETYLATION; PROFILING
REVEALS; DEFICIENT MICE; TRANSCRIPTION; METABOLISM; BETA;
DIFFERENTIATION; STAGGERER
AB In this study, we demonstrate that the lack of retinoic acid-related orphan receptor (ROR) gamma or alpha expression in mice significantly reduced the peak expression level of Cry1, Bmal1, E4bp4, Rev-Erb alpha and Per2 in an ROR isotype- and tissue-selective manner without affecting the phase of their rhythmic expression. Analysis of ROR gamma/ROR alpha double knockout mice indicated that in certain tissues ROR gamma and ROR alpha exhibited a certain degree of redundancy in regulating clock gene expression. Reporter gene analysis showed that ROR gamma was able to induce reporter gene activity through the RORE-containing regulatory regions of Cry1, Bmal1, Rev-Erb alpha and E4bp4. Co-expression of Rev-Erb alpha or addition of a novel ROR antagonist repressed this activation. ChIP-Seq and ChIP-Quantitative real-time polymerase chain reaction (QPCR) analysis demonstrated that in vivo ROR gamma regulate these genes directly and in a Zeitgeber time (ZT)-dependent manner through these ROREs. This transcriptional activation by RORs was associated with changes in histone acetylation and chromatin accessibility. The rhythmic expression of ROR gamma 1 by clock proteins may lead to the rhythmic expression of ROR gamma 1 target genes. The presence of ROR gamma binding sites and its down-regulation in ROR gamma(-/-) liver suggest that the rhythmic expression of Avpr1a depends on ROR gamma consistent with the concept that ROR gamma 1 provides a link between the clock machinery and its regulation of metabolic genes.
C1 [Takeda, Yukimasa; Jetten, Anton M.] NIEHS, Cell Biol Sect, NIH, Res Triangle Pk, NC 27709 USA.
[Jothi, Raja] NIEHS, Syst Biol Grp, Biostat Branch, Div Intramural Res,NIH, Res Triangle Pk, NC 27709 USA.
[Birault, Veronique] GlaxoSmithKline Ltd, Med Chem, Med Res Ctr, Stevenage, Herts, England.
RP Jetten, AM (reprint author), NIEHS, Cell Biol Sect, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM jetten@niehs.nih.gov
RI Jothi, Raja/G-3780-2015;
OI Jetten, Anton/0000-0003-0954-4445
FU National Institute of Environmental Health Sciences, National Institutes
of Health [Z01-ES-101586]; National Institute of Environmental Health
Sciences, National Institutes of Health
FX Intramural Research Program of the National Institute of Environmental
Health Sciences, National Institutes of Health [Z01-ES-101586]. Funding
for open access charge: National Institute of Environmental Health
Sciences, National Institutes of Health.
NR 55
TC 40
Z9 43
U1 2
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 2012
VL 40
IS 17
BP 8519
EP 8535
DI 10.1093/nar/gks630
PG 17
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 015RS
UT WOS:000309464300038
PM 22753030
ER
PT J
AU Carmel, L
Koonin, EV
Dracheva, S
AF Carmel, Liran
Koonin, Eugene V.
Dracheva, Stella
TI Dependencies among Editing Sites in Serotonin 2C Receptor mRNA
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID 5-HT2C RECEPTORS; CONSTITUTIVE ACTIVITY; HUMAN BRAIN; ADAR2; SUICIDE;
GENE; IDENTIFICATION; TRANSCRIPTOME; PHARMACOLOGY; SELECTIVITY
AB The serotonin 2C receptor (5-HT2CR)-a key regulator of diverse neurological processes-exhibits functional variability derived from editing of its pre-mRNA by site-specific adenosine deamination (A-to-I pre-mRNA editing) in five distinct sites. Here we describe a statistical technique that was developed for analysis of the dependencies among the editing states of the five sites. The statistical significance of the observed correlations was estimated by comparing editing patterns in multiple individuals. For both human and rat 5-HT2CR, the editing states of the physically proximal sites A and B were found to be strongly dependent. In contrast, the editing states of sites C and D, which are also physically close, seem not to be directly dependent but instead are linked through the dependencies on sites A and B, respectively. We observed pronounced differences between the editing patterns in humans and rats: in humans site A is the key determinant of the editing state of the other sites, whereas in rats this role belongs to site B. The structure of the dependencies among the editing sites is notably simpler in rats than it is in humans implying more complex regulation of 5-HT2CR editing and, by inference, function in the human brain. Thus, exhaustive statistical analysis of the 5-HT2CR editing patterns indicates that the editing state of sites A and B is the primary determinant of the editing states of the other three sites, and hence the overall editing pattern. Taken together, these findings allow us to propose a mechanistic model of concerted action of ADAR1 and ADAR2 in 5-HT2CR editing. Statistical approach developed here can be applied to other cases of interdependencies among modification sites in RNA and proteins.
C1 [Carmel, Liran] Hebrew Univ Jerusalem, Dept Genet, Alexander Silberman Inst Life Sci, Fac Sci, IL-91904 Jerusalem, Israel.
[Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Dracheva, Stella] James J Peters Vet Affairs Med Ctr, Bronx, NY USA.
[Dracheva, Stella] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA.
RP Carmel, L (reprint author), Hebrew Univ Jerusalem, Dept Genet, Alexander Silberman Inst Life Sci, Fac Sci, J Safra Campus, IL-91904 Jerusalem, Israel.
EM Stella.Dracheva@mssm.edu
FU European Union Marie Curie International Reintegration Grant
[PIRG05-GA-2009-248639]; Lohenstein August and Elza Foundation;
Intramural Program of the US Department of Health and Human Services
(National Library of Medicine, NIH); VA Merit award; NIMH grant
[MH090352]; Hope for Depression Foundation grant; VISN3 Mental Illness
Research and Education Clinical Center (MIRECC)
FX LC was supported by the European Union Marie Curie International
Reintegration Grant (PIRG05-GA-2009-248639), and by the Lohenstein
August and Elza Foundation. EVK is supported by the Intramural Program
of the US Department of Health and Human Services (National Library of
Medicine, NIH). SD is supported by VA Merit award, NIMH MH090352 grant,
the Hope for Depression Foundation grant, and by the VISN3 Mental
Illness Research and Education Clinical Center (MIRECC). The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 43
TC 2
Z9 3
U1 0
U2 3
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 2012
VL 8
IS 9
AR e1002663
DI 10.1371/journal.pcbi.1002663
PG 13
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA 016IJ
UT WOS:000309510900008
PM 22969417
ER
PT J
AU Gething, PW
Elyazar, IRF
Moyes, CL
Smith, DL
Battle, KE
Guerra, CA
Patil, AP
Tatem, AJ
Howes, RE
Myers, MF
George, DB
Horby, P
Wertheim, HFL
Price, RN
Mueller, I
Baird, K
Hay, SI
AF Gething, Peter W.
Elyazar, Iqbal R. F.
Moyes, Catherine L.
Smith, David L.
Battle, Katherine E.
Guerra, Carlos A.
Patil, Anand P.
Tatem, Andrew J.
Howes, Rosalind E.
Myers, Monica F.
George, Dylan B.
Horby, Peter
Wertheim, Heiman F. L.
Price, Ric N.
Mueeller, Ivo
Baird, Kevin
Hay, Simon I.
TI A Long Neglected World Malaria Map: Plasmodium vivax Endemicity in 2010
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID DUFFY-BLOOD-GROUP; ARTEMISININ COMBINATION THERAPY; BRAZILIAN AMAZON
REGION; NEW-GUINEAN CHILDREN; FALCIPARUM-MALARIA; P. VIVAX; ATLAS
PROJECT; PARASITE RATE; RISK-FACTORS; TRANSMISSION
AB Background: Current understanding of the spatial epidemiology and geographical distribution of Plasmodium vivax is far less developed than that for P. falciparum, representing a barrier to rational strategies for control and elimination. Here we present the first systematic effort to map the global endemicity of this hitherto neglected parasite.
Methodology and Findings: We first updated to the year 2010 our earlier estimate of the geographical limits of P. vivax transmission. Within areas of stable transmission, an assembly of 9,970 geopositioned P. vivax parasite rate (PvPR) surveys collected from 1985 to 2010 were used with a spatiotemporal Bayesian model-based geostatistical approach to estimate endemicity age-standardised to the 1-99 year age range (PvPR(1-99)) within every 5x5 km resolution grid square. The model incorporated data on Duffy negative phenotype frequency to suppress endemicity predictions, particularly in Africa. Endemicity was predicted within a relatively narrow range throughout the endemic world, with the point estimate rarely exceeding 7% PvPR(1-99). The Americas contributed 22% of the global area at risk of P. vivax transmission, but high endemic areas were generally sparsely populated and the region contributed only 6% of the 2.5 billion people at risk (PAR) globally. In Africa, Duffy negativity meant stable transmission was constrained to Madagascar and parts of the Horn, contributing 3.5% of global PAR. Central Asia was home to 82% of global PAR with important high endemic areas coinciding with dense populations particularly in India and Myanmar. South East Asia contained areas of the highest endemicity in Indonesia and Papua New Guinea and contributed 9% of global PAR.
Conclusions and Significance: This detailed depiction of spatially varying endemicity is intended to contribute to a much-needed paradigm shift towards geographically stratified and evidence-based planning for P. vivax control and elimination.
C1 [Gething, Peter W.; Moyes, Catherine L.; Battle, Katherine E.; Guerra, Carlos A.; Patil, Anand P.; Howes, Rosalind E.; Myers, Monica F.; Hay, Simon I.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford OX1 3PS, England.
[Elyazar, Iqbal R. F.; Baird, Kevin] Eijkman Oxford Clin Res Unit, Jakarta, Indonesia.
[Smith, David L.] Johns Hopkins Bloomberg Sch Publ Hlth, Johns Hopkins Malaria Res Inst, Baltimore, MD USA.
[Smith, David L.; Tatem, Andrew J.; George, Dylan B.; Hay, Simon I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Tatem, Andrew J.] Univ Florida, Dept Geog, Gainesville, FL 32611 USA.
[Tatem, Andrew J.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL 32611 USA.
[Horby, Peter; Wertheim, Heiman F. L.] Wellcome Trust Major Overseas Programme, Oxford Univ Clin Res Unit, Ho Chi Minh City, Vietnam.
[Horby, Peter; Wertheim, Heiman F. L.; Price, Ric N.; Baird, Kevin] Univ Oxford, Ctr Trop Med, Nuffield Dept Med, Oxford, England.
[Price, Ric N.] Charles Darwin Univ, Menzies Sch Hlth Res, Global Hlth Div, Darwin, NT 0909, Australia.
[Price, Ric N.] Royal Darwin Hosp, Div Med, Darwin, NT, Australia.
[Mueeller, Ivo] Papua New Guinea Inst Med Res, Goroka, Papua N Guinea.
RP Gething, PW (reprint author), Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, S Parks Rd, Oxford OX1 3PS, England.
EM peter.gething@zoo.ox.ac.uk; simon.i.hay@gmail.com
RI Mueller, Ivo/C-7251-2013; Horby, Peter/D-1585-2013; Hay,
Simon/F-8967-2015; Smith, David/L-8850-2013; Wertheim,
Heiman/F-3338-2016
OI Price, Richard/0000-0003-2000-2874; Mueller, Ivo/0000-0001-6554-6889;
Hay, Simon/0000-0002-0611-7272; Horby, Peter/0000-0002-9822-1586;
Gething, Peter/0000-0001-6759-5449; Battle,
Katherine/0000-0003-2401-2615; Moyes, Catherine/0000-0002-8028-4079;
Smith, David/0000-0003-4367-3849; Wertheim, Heiman/0000-0002-5003-5565
FU Wellcome Trust [095066, 091835, 085406, 089276/Z/09/Z, B9RJIXO];
University of Oxford-Li Ka Shing Foundation Global Health Program;
Oxford Tropical Network; Bill and Melinda Gates Foundation [49446,
1032350]; Li Ka Shing Foundation; RAPIDD program of the Science and
Technology Directorate; Department of Homeland Security; Fogarty
International Center, National Institutes of Health; Wellcome Trust, UK;
Global Fund to Fight AIDS, Tuberculosis, and Malaria
FX SIH is funded by a Senior Research Fellowship from the Wellcome Trust
(#095066), which also supports PWG, CAG, and KEB. CLM and APP are funded
by a Biomedical Resources Grant from the Wellcome Trust (#091835). REH
is funded by a Biomedical Resources Grant from the Wellcome Trust
(#085406). IRFE is funded by grants from the University of Oxford-Li Ka
Shing Foundation Global Health Program and the Oxford Tropical Network.
DLS and AJT are supported by grants from the Bill and Melinda Gates
Foundation (#49446, #1032350) (http://www.gatesfoundation.org). PH is
supported by Wellcome Trust grants 089276/Z/09/Z and the Li Ka Shing
Foundation. RNP is a Wellcome Trust Senior Fellow in Clinical Science
(#091625). JKB is supported by a Wellcome Trust grant (#B9RJIXO). PWG,
APP, DLS, AJT, DBG, and SIH also acknowledge support from the RAPIDD
program of the Science and Technology Directorate, Department of
Homeland Security, and the Fogarty International Center, National
Institutes of Health (http://www.fic.nih.gov). This work forms part of
the output of the Malaria Atlas Project (MAP, http://www.map.ox.ac.uk),
principally funded by the Wellcome Trust, UK
(http://www.wellcome.ac.uk). MAP also acknowledges the support of the
Global Fund to Fight AIDS, Tuberculosis, and Malaria
(http://www.theglobalfund.org). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 109
TC 184
Z9 186
U1 9
U2 47
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD SEP
PY 2012
VL 6
IS 9
AR e1814
DI 10.1371/journal.pntd.0001814
PG 12
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 016OH
UT WOS:000309528100017
PM 22970336
ER
PT J
AU Enewold, L
Mechanic, LE
Bowman, ED
Platz, EA
Alberg, AJ
AF Enewold, Lindsey
Mechanic, Leah E.
Bowman, Elise D.
Platz, Elizabeth A.
Alberg, Anthony J.
TI Association of Matrix Metalloproteinase-1 Polymorphisms with Risk of
COPD and Lung Cancer and Survival in Lung Cancer
SO ANTICANCER RESEARCH
LA English
DT Article
DE Lung cancer; case-control; survival; chronic bronchitis; emphysema;
matrix metalloproteinase-1; gene polymorphism; rs11292517
ID MATRIX-METALLOPROTEINASE-1; PROMOTER; EXPRESSION; SUSCEPTIBILITY;
EMPHYSEMA; MMP1
AB Background: The primary risk factor for chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC) is cigarette smoking but shared susceptibility factors, such as variations in the matrix metalloproteinase-1 (MMPI) gene, may also underlie both diseases. Materials and Methods: Cases with prevalent COPD (n=167), incident NSCLC (n=242), or prevalent COPD plus incident NSCLC (n=128) were compared to disease-free controls (n=338) to assess six MMP1 polymorphisms. The association between these polymorphisms and survival in NSCLC was also evaluated. Results: Rs11292517 among African-Americans [odds ratio (OR)=5.48, 95% confidence interval (CI)=1.17-25.72] and rs2071230 among Caucasians (OR=2.51, 95% CI=1.09-5.77) appeared to be associated with NSCLC risk in the presence of COPD. Rs470558 appeared to be associated with survival in NSCLC among African-Americans (hazard ratio=3.94; 95%CI=1.14-13.63). No associations remained after adjusting for multiple comparisons. Conclusion: Polymorphisms in MMPI were not consistently associated with prevalent COPD or incident NSCLC nor with survival in NSCLC.
C1 [Enewold, Lindsey] US Mil Canc Inst, Henry M Jackson Fdn, Rockville, MD 20852 USA.
[Enewold, Lindsey; Platz, Elizabeth A.; Alberg, Anthony J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Mechanic, Leah E.; Bowman, Elise D.] NCI, Ctr Canc Res, Human Carcinogenesis Lab, Baltimore, MD USA.
[Alberg, Anthony J.] Med Univ S Carolina, Hollings Canc Ctr, Canc Prevent & Control Program, Charleston, SC 29425 USA.
RP Enewold, L (reprint author), US Mil Canc Inst, Henry M Jackson Fdn, 11300 Rockville Pike,Suite 1215, Rockville, MD 20852 USA.
EM lenewold@yahoo.com
FU NIH; NCI; CCR; National Institute of Environmental Health Sciences [ES
07141]
FX This research was supported by the Intramural Research Program of the
NIH, NCI and CCR. L.E. was supported by a National Institute of
Environmental Health Sciences Training Grant [ES 07141].
NR 22
TC 1
Z9 1
U1 0
U2 0
PU INT INST ANTICANCER RESEARCH
PI ATHENS
PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22,
ATHENS 19014, GREECE
SN 0250-7005
J9 ANTICANCER RES
JI Anticancer Res.
PD SEP
PY 2012
VL 32
IS 9
BP 3917
EP 3922
PG 6
WC Oncology
SC Oncology
GA 012NN
UT WOS:000309243200041
PM 22993337
ER
PT J
AU Enewold, L
Mechanic, LE
Bowman, ED
Platz, EA
Alberg, AJ
AF Enewold, Lindsey
Mechanic, Leah E.
Bowman, Elise D.
Platz, Elizabeth A.
Alberg, Anthony J.
TI SERPINA1 and ELA2 Polymorphisms Are Not Associated with COPD or Lung
Cancer
SO ANTICANCER RESEARCH
LA English
DT Article
DE Lung cancer; case-control; chronic bronchitis; emphysema; alpha1
antitrypsin; neutrophil elastase; gene polymorphism; SNPs
ID OBSTRUCTIVE PULMONARY-DISEASE; NEUTROPHIL ELASTASE GENE;
ALPHA(1)-ANTITRYPSIN DEFICIENCY; PROMOTER REGION; RISK; EPIDEMIOLOGY;
METAANALYSIS; EMPHYSEMA; ALLELE; LOCUS
AB Background: Through their roles in tissue remodeling, variants in the genes that encode alpha1-antitrypsin (AAT) and neutrophil elastase (NE) were hypothesized to be associated with the risk of both chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC). Materials and Methods: Cases with prevalent COPD (n=145), incident NSCLC (n=203) or prevalent COPD plus NSCLC (n=118) were compared to disease-free controls (n=317), to assess two functional polymorphisms in serpin peptidase inhibitor, clade A, member 1 (SERPINA1), which encodes AAT, and eleven tagging polymorphisms in and around elastase 2 (ELA2), which encodes NE. All analyses were stratified by race. Results: Among African-Americans, the less efficient SERPINA1 variant appeared to be associated with increased risk of prevalent COPD but only in the presence of NSCLC (odds ratio=7.39; 95% confidence interval=1.03-53.21) and not after correcting for multiple comparisons. Conclusion: Variations in SERPINA1 and ELA2 were not consistently or strongly associated with the risk of either COPD or NSCLC in either race.
C1 [Enewold, Lindsey] US Mil Canc Inst, Henry M Jackson Fdn, Rockville, MD 20852 USA.
[Enewold, Lindsey; Platz, Elizabeth A.; Alberg, Anthony J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Mechanic, Leah E.; Bowman, Elise D.] NCI, Ctr Canc Res, Human Carcinogenesis Lab, Bethesda, MD USA.
[Alberg, Anthony J.] Med Univ S Carolina, Hollings Canc Ctr, Canc Prevent & Control Program, Charleston, SC 29425 USA.
RP Enewold, L (reprint author), US Mil Canc Inst, Henry M Jackson Fdn, 11300 Rockville Pike,Suite 1215, Rockville, MD 20852 USA.
EM lenewold@yahoo.com
FU NIH; NCI; CCR; National Institute of Environmental Health Sciences [ES
07141]
FX This research was supported by the Intramural Research Program of the
NIH, NCI and CCR. L.E. was supported by a National Institute of
Environmental Health Sciences Training Grant [ES 07141].
NR 27
TC 0
Z9 0
U1 0
U2 2
PU INT INST ANTICANCER RESEARCH
PI ATHENS
PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22,
ATHENS 19014, GREECE
SN 0250-7005
J9 ANTICANCER RES
JI Anticancer Res.
PD SEP
PY 2012
VL 32
IS 9
BP 3923
EP 3928
PG 6
WC Oncology
SC Oncology
GA 012NN
UT WOS:000309243200042
PM 22993338
ER
PT J
AU Chong, A
Wehrly, TD
Child, R
Hansen, B
Hwang, S
Virgin, HW
Celli, J
AF Chong, Audrey
Wehrly, Tara D.
Child, Robert
Hansen, Bryan
Hwang, Seungmin
Virgin, Herbert W.
Celli, Jean
TI Cytosolic clearance of replication-deficient mutants reveals Francisella
tularensis interactions with the autophagic pathway
SO AUTOPHAGY
LA English
DT Article
DE Francisella; pathogenesis; cytosol; autophagy; clearance; LC3;
ubiquitin; SQSTM1/p62
ID LIVE VACCINE STRAIN; HOST-CELL DEATH; SELECTIVE AUTOPHAGY; BACTERIAL
PATHOGENS; HUMAN MACROPHAGES; PURINE AUXOTROPH; IFN-GAMMA; SCHU S4;
ESCAPE; TARGETS
AB Cytosolic bacterial pathogens must evade intracellular innate immune recognition and clearance systems such as autophagy to ensure their survival and proliferation. The intracellular cycle of the bacterium Francisella tularensis is characterized by rapid phagosomal escape followed by extensive proliferation in the macrophage cytoplasm. Cytosolic replication, but not phagosomal escape, requires the locus FTT0369c, which encodes the dipA gene (deficient in intracellular replication A). Here, we show that a replication-deficient, Delta dipA mutant of the prototypical SchuS4 strain is eventually captured from the cytosol of murine and human macrophages into double-membrane vacuoles displaying the late endosomal marker, LAMP1, and the autophagy-associated protein, LC3, coinciding with a reduction in viable intracellular bacteria. Capture of SchuS4 Delta dipA was not dipA-specific as other replication-deficient bacteria, such as chloramphenicol-treated SchuS4 and a purine auxotroph mutant SchuS4 Delta purMCD, were similarly targeted to autophagic vacuoles. Vacuoles containing replication-deficient bacteria were labeled with ubiquitin and the autophagy receptors SQSTM1/p62 and NBR1, and their formation was decreased in macrophages from either ATG5-, LC3B-or SQSTM1-deficient mice, indicating recognition by the ubiquitin-SQSTM1-LC3 pathway. While a fraction of both the wild-type and the replication-impaired strains were ubiquitinated and recruited SQSTM1, only the replication-defective strains progressed to autophagic capture, suggesting that wild-type Francisella interferes with the autophagic cascade. Survival of replication-deficient strains was not restored in autophagy-deficient macrophages, as these bacteria died in the cytosol prior to autophagic capture. Collectively, our results demonstrate that replication-impaired strains of Francisella are cleared by autophagy, while replication-competent bacteria seem to interfere with autophagic recognition, therefore ensuring survival and proliferation.
C1 [Chong, Audrey; Wehrly, Tara D.; Child, Robert; Celli, Jean] NIAID, NIH, Lab Intracellular Parasites, Tularemia Pathogenesis Sect, Hamilton, MT USA.
[Hansen, Bryan] NIAID, NIH, Rocky Mt Labs, Elect Microscopy Unit,Res Technol Branch, Hamilton, MT USA.
[Hwang, Seungmin; Virgin, Herbert W.] Univ Sch Med, Dept Pathol & Immunol, St Louis, MO USA.
[Virgin, Herbert W.] Washington Univ, Sch Med, Midwest Reg Ctr Excellence Biodef & Emerging Inf, St Louis, MO USA.
RP Celli, J (reprint author), NIAID, NIH, Lab Intracellular Parasites, Tularemia Pathogenesis Sect, Hamilton, MT USA.
EM jcelli@niaid.nih.gov
OI Hwang, Seungmin/0000-0003-0846-5462
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases
FX We thank Preeti Malik-Kale and Olivia Steele-Mortimer for providing
human peripheral blood monocytes. This work was supported by the
Intramural Research Program of the National Institutes of Health,
National Institute of Allergy and Infectious Diseases.
NR 63
TC 39
Z9 40
U1 0
U2 13
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1554-8627
J9 AUTOPHAGY
JI Autophagy
PD SEP
PY 2012
VL 8
IS 9
BP 1342
EP 1356
DI 10.4161/auto.20808
PG 15
WC Cell Biology
SC Cell Biology
GA 003TO
UT WOS:000308634400007
PM 22863802
ER
PT J
AU Liu, W
Phang, JM
AF Liu, Wei
Phang, James M.
TI Proline dehydrogenase (oxidase), a mitochondrial tumor suppressor, and
autophagy under the hypoxia microenvironment
SO AUTOPHAGY
LA English
DT Article
DE proline dehydrogenase/oxidase; metabolic stress; hypoxia; autophagy;
apoptosis
AB Proline dehydrogenase (oxidase, PRODH/POX), the first enzyme in the pathway of proline catabolism, has been identified as a mitochondrial, metabolic tumor suppressor, which is downregulated in a variety of human tumors. However, our recent findings show that PRODH/POX is upregulated by hypoxia in vitro and in vivo. The combination of low glucose and hypoxia produces additive effects on PRODH/POX expression. Both hypoxia and glucose depletion enhance PRODH/POX expression through AMP-activated protein kinase (AMPK) activation to promote tumor cell survival. Nevertheless, the mechanisms underlying PRODH/POX prosurvival functions are different for hypoxia and low-glucose conditions. Glucose depletion with or without hypoxia elevates PRODH/POX and proline utilization to supply ATP for cellular energy needs. Interestingly, under hypoxia PRODH/POX induces protective autophagy by generating reactive oxygen species (ROS). AMPK is the main initiator of stress-triggered autophagy. Thus, PRODH/POX acts as a downstream effector of AMPK in the activation of autophagy under hypoxia. This regulation was confirmed to be independent of the mechanistic target of rapamycin (MTOR) pathway, a major downstream target of AMPK signaling.
C1 [Liu, Wei; Phang, James M.] NIH, Frederick Natl Lab Canc Res, Ctr Canc Res, Metab & Canc Susceptibil Sect,Basic Res Lab, Frederick, MD USA.
RP Phang, JM (reprint author), NIH, Frederick Natl Lab Canc Res, Ctr Canc Res, Metab & Canc Susceptibil Sect,Basic Res Lab, Frederick, MD USA.
EM phangj@mail.nih.gov
RI liu, wei /E-7340-2012
NR 0
TC 11
Z9 11
U1 0
U2 6
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1554-8627
J9 AUTOPHAGY
JI Autophagy
PD SEP
PY 2012
VL 8
IS 9
BP 1407
EP 1409
DI 10.4161/auto.21152
PG 3
WC Cell Biology
SC Cell Biology
GA 003TO
UT WOS:000308634400019
PM 22885468
ER
PT J
AU Zhang, ZW
Chen, Z
Troendle, JF
Zhang, J
AF Zhang, Zhiwei
Chen, Zhen
Troendle, James F.
Zhang, Jun
TI Causal Inference on Quantiles with an Obstetric Application
SO BIOMETRICS
LA English
DT Article
DE Double robustness; Inverse probability weighting; Missing data; Outcome
regression; Propensity score; Stratification; Subclassification
ID DOUBLY ROBUST ESTIMATION; PROPENSITY SCORE; INCOMPLETE DATA; MISSING
DATA; MODELS; BIAS
AB The current statistical literature on causal inference is primarily concerned with population means of potential outcomes, while the current statistical practice also involves other meaningful quantities such as quantiles. Motivated by the Consortium on Safe Labor (CSL), a large observational study of obstetric labor progression, we propose and compare methods for estimating marginal quantiles of potential outcomes as well as quantiles among the treated. By adapting existing methods and techniques, we derive estimators based on outcome regression (OR), inverse probability weighting, and stratification, as well as a doubly robust (DR) estimator. By incorporating stratification into the DR estimator, we further develop a hybrid estimator with enhanced numerical stability at the expense of a slight bias under misspecification of the OR model. The proposed methods are illustrated with the CSL data and evaluated in simulation experiments mimicking the CSL.
C1 [Zhang, Zhiwei] US FDA, Div Biostat, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
[Chen, Zhen] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA.
[Troendle, James F.] NHLBI, Off Biostat Res, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
[Zhang, Jun] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, MOE, Shanghai 200092, Peoples R China.
[Zhang, Jun] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Shanghai Key Lab Childrens Environm Hlth, Shanghai 200092, Peoples R China.
RP Zhang, ZW (reprint author), US FDA, Div Biostat, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
EM zhiwei.zhang@fda.hhs.gov
NR 28
TC 2
Z9 2
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0006-341X
J9 BIOMETRICS
JI Biometrics
PD SEP
PY 2012
VL 68
IS 3
BP 697
EP 706
DI 10.1111/j.1541-0420.2011.01712.x
PG 10
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology; Mathematics
GA 011RW
UT WOS:000309183600007
PM 22150612
ER
PT J
AU Berger, VW
AF Berger, Vance W.
TI Comment on Proschan et al. (2011), Out of the Frying Pan and in to the
Fire?'"
SO BIOMETRICS
LA English
DT Letter
C1 NCI, Biometry Res Grp, Bethesda, MD 20892 USA.
RP Berger, VW (reprint author), NCI, Biometry Res Grp, Execut Plaza N,Suite 3131,6130 Execut Blvd,MSC 73, Bethesda, MD 20892 USA.
EM vb78c@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 0006-341X
J9 BIOMETRICS
JI Biometrics
PD SEP
PY 2012
VL 68
IS 3
BP 990
EP 990
PG 1
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology; Mathematics
GA 011RW
UT WOS:000309183600037
PM 23013224
ER
PT J
AU Proschan, M
Brittain, E
Kammerman, L
AF Proschan, Michael
Brittain, Erica
Kammerman, Lisa
TI Comment on Proschan et al. (2011), Out of the Frying Pan and in to the
Fire?
SO BIOMETRICS
LA English
DT Letter
C1 [Proschan, Michael; Brittain, Erica] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA.
[Kammerman, Lisa] US FDA, Div Biometr 3, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
RP Proschan, M (reprint author), NIAID, Biostat Res Branch, 6700A Rockledge Dr,Room 5140, Bethesda, MD 20892 USA.
EM ProschaM@niaid.nih.gov
NR 4
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0006-341X
J9 BIOMETRICS
JI Biometrics
PD SEP
PY 2012
VL 68
IS 3
BP 990
EP 991
PG 2
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology; Mathematics
GA 011RW
UT WOS:000309183600038
ER
PT J
AU Baker, SG
AF Baker, Stuart G.
TI Comments on Nie et al. (2011), Biometrics, Early View"
SO BIOMETRICS
LA English
DT Letter
C1 NCI, Biometry Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Baker, SG (reprint author), NCI, Biometry Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
EM sb16i@nih.gov
NR 3
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0006-341X
J9 BIOMETRICS
JI Biometrics
PD SEP
PY 2012
VL 68
IS 3
BP 992
EP 992
PG 1
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology; Mathematics
GA 011RW
UT WOS:000309183600039
PM 23013226
ER
PT J
AU Clough, E
Oliver, B
AF Clough, Emily
Oliver, Brian
TI Genomics of sex determination in Drosophila
SO BRIEFINGS IN FUNCTIONAL GENOMICS
LA English
DT Article
DE drosophila; transcriptome; sex determination; effector; selector
ID BIASED GENE-EXPRESSION; GENITAL IMAGINAL DISC; ZINC-FINGER PROTEIN;
DOUBLESEX PROTEINS; DETERMINATION HIERARCHY; MOLECULAR ANALYSIS;
TRANSFORMER GENE; MELANOGASTER; DIFFERENTIATION; GERMLINE
AB Drosophilists have identified many, or perhaps most, of the key regulatory genes determining sex using classical genetics, however, regulatory genes must ultimately result in the deployment of the genome in a quantitative manner, replete with complex interactions with other regulatory pathways. In the last decade, genomics has provided a rich picture of the transcriptional profile of the sexes that underlies sexual dimorphism. The current challenge is linking transcriptional profiles with the regulatory genes. This will be a complex synthesis, but the prospects for progress are outstanding.
C1 [Clough, Emily] Columbia Univ, New York, NY 10027 USA.
[Oliver, Brian] Case Western Reserve Univ, Antony Mahowald Lab, Cleveland, OH 44106 USA.
[Oliver, Brian] Bruce Baker Lab, Stanford, CA USA.
RP Clough, E (reprint author), NIDDKD, Sect Dev Genom, NIH, 50 South Dr, Bethesda, MD 20892 USA.
EM cloughea@mail.nih.gov
FU NIH, NIDDK
FX We thank our colleagues in the lab for many discussions and comments on
the manuscript. This work supported by the Intramural Research Program
of the NIH, NIDDK.
NR 81
TC 8
Z9 8
U1 4
U2 26
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 2041-2649
J9 BRIEF FUNCT GENOMICS
JI Brief. Funct. Genomics
PD SEP
PY 2012
VL 11
IS 5
SI SI
BP 387
EP 394
DI 10.1093/bfgp/els019
PG 8
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 015PQ
UT WOS:000309458800007
PM 23023665
ER
PT J
AU Wu, JY
Shen, EJ
Shi, DS
Sun, ZS
Cai, T
AF Wu, Jinyu
Shen, Enjian
Shi, Dashuang
Sun, ZhongSheng
Cai, Tao
TI Identification of a novel Cys146X mutation of SOD1 in familial
amyotrophic lateral sclerosis by whole-exome sequencing
SO GENETICS IN MEDICINE
LA English
DT Article
DE amyotrophic lateral sclerosis (ALS); motor neuron disease; mutation;
superoxide dismutase 1 gene (SOD1); whole-exome sequencing
ID SUPEROXIDE-DISMUTASE; ALS; GENETICS; PROGRAM; ONSET
AB Purpose: Familial amyotrophic lateral sclerosis has been linked to mutations in 15 genes, and it is believed these genes account for less than 20-30% of Chinese patients with familial amyotrophic lateral sclerosis. Of the 163 different superoxide dismutase 1 gene mutations in arnyotrophic lateral sclerosis 1, only 6.1% of them were from individuals of Chinese origin. Therefore, to quickly learn the causative gene for patients with familial amyotrophic lateral sclerosis in a Chinese pedigree, we opted to apply whole-exome sequencing as a diagnostic tool.
Methods: To avoid time-consuming screening of known familial amyotrophic lateral sclerosis candidate genes by PCR-Sanger sequencing, we conducted whole-exome sequencing toward selected individuals of a four-generation familial amyotrophic lateral sclerosis family.
Results: Patients in the family showed autosomal dominant features, as well as a mean onset age of 35.3 years, and a mean duration of 2.1 years. By deep sequencing analysis, we identified a novel p.Cys146X SOD1 mutation in all examined patients. Genotype-phenotype and SOD1 structural model analysis revealed the effects of the Cys57-Cys146 disulfide bond formation and the C-terminal dimer contact region on the disease phenotypes.
Conclusion: The Cys146X mutation causes familial amyotrophic lateral sclerosis with severe phenotypes. Whole-exome sequencing becomes an attractive diagnostic tool for identifying causative genes, particularly for neurological disorders with unusual phenotypes, pleiotropic malformations, multiple known candidate genes, and complicated inheritance patterns.
C1 [Wu, Jinyu; Shen, Enjian; Sun, ZhongSheng; Cai, Tao] Wenzhou Med Coll, Inst Genom Med, Wenzhou, Peoples R China.
[Shi, Dashuang] George Washington Univ, Med Genet Res Ctr, Washington, DC USA.
[Shi, Dashuang] George Washington Univ, Childrens Natl Med Ctr, Dept Integrat Syst Biol, Washington, DC USA.
[Sun, ZhongSheng] Chinese Acad Sci, Beijing Inst Life Sci, Beijing, Peoples R China.
[Cai, Tao] Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD USA.
RP Sun, ZS (reprint author), Wenzhou Med Coll, Inst Genom Med, Wenzhou, Peoples R China.
EM sunzs@mail.biols.ac.cn; tcai@mail.nih.gov
FU National Natural Science Foundation of China [81110114]; Natural Science
Foundation of Zhejiang Province [Z2110521]
FX We thank the patients and their families for their participation in this
study. We thank the National Key Laboratory of Medical Genetics, at
Changsha, for assisting in DNA sample collection in this study. This
work was supported by the National Natural Science Foundation of China
(81110114) and the Natural Science Foundation of Zhejiang Province
(Z2110521).
NR 20
TC 8
Z9 8
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1098-3600
J9 GENET MED
JI Genet. Med.
PD SEP
PY 2012
VL 14
IS 9
BP 823
EP 826
DI 10.1038/gim.2012.50
PG 4
WC Genetics & Heredity
SC Genetics & Heredity
GA 005RN
UT WOS:000308767600009
PM 22595939
ER
PT J
AU Westgeest, KB
de Graaf, M
Fourment, M
Bestebroer, TM
van Beek, R
Spronken, MIJ
de Jong, JC
Rimmelzwaan, GF
Russell, CA
Osterhaus, ADME
Smith, GJD
Smith, DJ
Fouchier, RAM
AF Westgeest, Kim B.
de Graaf, Miranda
Fourment, Mathieu
Bestebroer, Theo M.
van Beek, Ruud
Spronken, Monique I. J.
de Jong, Jan C.
Rimmelzwaan, Guus F.
Russell, Colin A.
Osterhaus, Albert D. M. E.
Smith, Gavin J. D.
Smith, Derek J.
Fouchier, Ron A. M.
TI Genetic evolution of the neuraminidase of influenza A (H3N2) viruses
from 1968 to 2009 and its correspondence to haemagglutinin evolution
SO JOURNAL OF GENERAL VIROLOGY
LA English
DT Article
ID PHYLOGENETIC ANALYSIS; ANTIGENIC VARIATION; MAXIMUM-LIKELIHOOD; RNA
VIRUSES; 3-DIMENSIONAL STRUCTURE; SIALIC-ACID; AMINO-ACID; SEQUENCES;
VARIANTS; ANTIBODY
AB Each year, influenza viruses cause epidemics by evading pre-existing humoral immunity through mutations in the major glycoproteins: the haemagglutinin (HA) and the neuraminidase (NA). In 2004, the antigenic evolution of HA of human influenza A (H3N2) viruses was mapped (Smith et al., Science 305, 371-376, 2004) from its introduction in humans in 1968 until 2003. The current study focused on the genetic evolution of NA and compared it with HA using the dataset of Smith and colleagues, updated to the epidemic of the 2009/2010 season. Phylogenetic trees and genetic maps were constructed to visualize the genetic evolution of NA and HA. The results revealed multiple reassortment events over the years. Overall rates of evolutionary change were lower for NA than for HA1 at the nucleotide level. Selection pressures were estimated, revealing an abundance of negatively selected sites and sparse positively selected sites. The differences found between the evolution of NA and HA1 warrant further analysis of the evolution of NA at the phenotypic level, as has been done previously for HA.
C1 [Westgeest, Kim B.; de Graaf, Miranda; Bestebroer, Theo M.; van Beek, Ruud; Spronken, Monique I. J.; de Jong, Jan C.; Rimmelzwaan, Guus F.; Osterhaus, Albert D. M. E.; Fouchier, Ron A. M.] Erasmus MC, Dept Virol, NL-3000 CA Rotterdam, Netherlands.
[de Graaf, Miranda; Russell, Colin A.; Smith, Derek J.] Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England.
[Fourment, Mathieu; Smith, Gavin J. D.] Duke NUS Grad Med Sch, Program Emerging Infect Dis, Singapore 169857, Singapore.
[Russell, Colin A.; Smith, Derek J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Fouchier, RAM (reprint author), Erasmus MC, Dept Virol, NL-3000 CA Rotterdam, Netherlands.
EM r.fouchier@erasmusmc.nl
RI Fourment, Mathieu/E-4665-2012; Fouchier, Ron/A-1911-2014;
OI Fouchier, Ron/0000-0001-8095-2869; Fourment,
Mathieu/0000-0001-8153-9822; Osterhaus, Albert/0000-0002-6074-1172;
Russell, Colin/0000-0002-2113-162X; Smith, Gavin JD/0000-0001-5031-468X
FU NWO-VICI grant; NIH [HHSN266200700010C]
FX The authors would gratefully like to thank Dr Mathilde Richard for
constructive discussions, Stefan van der Vliet and Oanh Vuong for
excellent technical assistance and Ton Marzec for providing part of the
influenza A (H3N2) virus isolates. We are grateful for the outstanding
training received at the 15th and 16th International Bioinformatics
Workshop on Virus Evolution and Molecular Epidemiology, September 2009,
Rotterdam and 2010, Baltimore
(http://regaweb.med.kuleuven.be/workshop/). This work was supported by
an NWO-VICI grant and NIH contract no. HHSN266200700010C.
NR 74
TC 17
Z9 22
U1 3
U2 19
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 0022-1317
J9 J GEN VIROL
JI J. Gen. Virol.
PD SEP
PY 2012
VL 93
BP 1996
EP 2007
DI 10.1099/vir.0.043059-0
PN 9
PG 12
WC Biotechnology & Applied Microbiology; Virology
SC Biotechnology & Applied Microbiology; Virology
GA 009OM
UT WOS:000309035100019
PM 22718569
ER
PT J
AU Cui, J
Tachedjian, G
Tachedjian, M
Holmes, EC
Zhang, SY
Wang, LF
AF Cui, Jie
Tachedjian, Gilda
Tachedjian, Mary
Holmes, Edward C.
Zhang, Shuyi
Wang, Lin-Fa
TI Identification of diverse groups of endogenous gammaretroviruses in
mega- and microbats
SO JOURNAL OF GENERAL VIROLOGY
LA English
DT Article
ID PRIMATE EVOLUTION; FRUIT BATS; RETROVIRUSES; ORIGIN; PHYLOGENIES;
RESERVOIRS; DISCOVERY; VIRUSES; DISEASE; HUMANS
AB A previous phylogenetic study suggested that mammalian gammaretroviruses may have originated in bats. Here we report the discovery of RNA transcripts from two putative endogenous gammaretroviruses in frugivorous (Rousettus leschenaultii retrovirus, RIRV) and insectivorous (Megaderma lyra retrovirus, MIRV) bat species. Both genomes possess a large deletion in pol, indicating that they are defective retroviruses. Phylogenetic analysis places RIRV and MIRV within the diversity of mammalian gammaretroviruses, with the former falling closer to porcine endogenous retroviruses and the latter to Mus dunni endogenous virus, koala retrovirus and gibbon ape leukemia virus. Additional genomic mining suggests that both microbat (Myotis lucifugus) and megabat (Pteropus vampyrus) genomes harbour many copies of endogenous retroviral forms related to RIRV and MIRV. Furthermore, phylogenetic analysis reveals the presence of three genetically diverse groups of endogenous gammaretroviruses in bat genomes, with M. lucifugus possessing members of all three groups. Taken together, this study indicates that bats harbour distinct gammaretroviruses and may have played an important role as reservoir hosts during the diversification of mammalian gammaretroviruses.
C1 [Cui, Jie; Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Tachedjian, Gilda] Burnet Inst, Ctr Virol, Retroviral Biol & Antivirals Lab, Melbourne, Vic 3004, Australia.
[Tachedjian, Gilda] Monash Univ, Dept Microbiol, Clayton, Vic 3168, Australia.
[Tachedjian, Gilda] Monash Univ, Dept Med, Melbourne, Vic 3004, Australia.
[Tachedjian, Mary; Wang, Lin-Fa] CSIRO Livestock Ind, Australian Anim Hlth Lab, Geelong, Vic 3220, Australia.
[Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Zhang, Shuyi] E China Normal Univ, Inst Adv Interdisciplinary Res, Inst Mol Ecol & Evolut, Shanghai 200062, Peoples R China.
[Wang, Lin-Fa] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3010, Australia.
RP Cui, J (reprint author), Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
EM jiecui@yahoo.com
OI Tachedjian, Gilda/0000-0002-7733-7037; Cui, Jie/0000-0001-8176-9951;
Holmes, Edward/0000-0001-9596-3552
FU National Health and Medical Research Council of Australia [543105];
CSIRO Office of the Chief Executive via an OCE Science Leader Award;
Institute of Molecular Ecology and Evolution, East China Normal
University
FX We thank Lina Wang and Mengyao Dai (Institute of Molecular Ecology and
Evolution, East China Normal University) for experimental support. G. T.
was supported by the National Health and Medical Research Council of
Australia Senior Research Fellowship 543105 and the Victorian
Operational Infrastructure Support Program was received by the Burnet
Institute. L.-F. W. was supported by the CSIRO Office of the Chief
Executive via an OCE Science Leader Award.
NR 25
TC 22
Z9 22
U1 1
U2 20
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 0022-1317
EI 1465-2099
J9 J GEN VIROL
JI J. Gen. Virol.
PD SEP
PY 2012
VL 93
BP 2037
EP 2045
DI 10.1099/vir.0.043760-0
PN 9
PG 9
WC Biotechnology & Applied Microbiology; Virology
SC Biotechnology & Applied Microbiology; Virology
GA 009OM
UT WOS:000309035100023
PM 22694899
ER
PT J
AU Feero, WG
Kuo, GM
Jenkins, JF
Rackover, MA
AF Feero, W. Gregory
Kuo, Grace M.
Jenkins, Jean F.
Rackover, Michael A.
TI Pharmacist education in the era of genomic medicine
SO JOURNAL OF THE AMERICAN PHARMACISTS ASSOCIATION
LA English
DT Review
DE Pharmacogenomics; pharmacogenetics; pharmacy education
ID PHARMACOGENOMICS; CURRICULA
AB Pharmacists are increasingly expected to incorporate an understanding of the genomic contributions to medication management in their daily practice, and a general consensus exists that many pharmacists are not adequately prepared to effectively make use of genomic information. In November 2011, the National Human Genome Research Institute of the National Institutes of Health convened a meeting to discuss the status of genomics education for pharmacists. A variety of pharmacist organizations and other stakeholder groups attended the 2-day event and explored the current status of pharmacist genomic education, barriers and facilitators to enhanced education, and important next steps to ensure that pharmacists are prepared for the coming decades. This report summarizes the background, content, and outcomes from this meeting.
C1 [Jenkins, Jean F.] NHGRI, Genom Healthcare Branch, NIH, Bethesda, MD 20892 USA.
[Feero, W. Gregory] Maine Dartmouth Family Med Residency, Augusta, GA USA.
[Kuo, Grace M.] Univ Calif San Diego, San Diego, CA 92103 USA.
[Rackover, Michael A.] Philadelphia Univ, Sch Sci & Hlth, Physician Assistant Program, Philadelphia, PA USA.
RP Jenkins, JF (reprint author), NHGRI, Genom Healthcare Branch, NIH, Bldg 31,Room 4B09,31 Ctr Dr, Bethesda, MD 20892 USA.
EM jean.jenkins@nih.gov
FU National Human Genome Research Institute of the National Institutes of
Health
FX The meeting described in this article was funded by the National Human
Genome Research Institute of the National Institutes of Health.
NR 23
TC 3
Z9 3
U1 0
U2 8
PU AMER PHARMACEUTICAL ASSOC
PI WASHINGTON
PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 USA
SN 1544-3191
J9 J AM PHARM ASSOC
JI J. Am. Pharm. Assoc.
PD SEP-OCT
PY 2012
VL 52
IS 5
BP E113
EP E121
DI 10.1331/JAPhA.2012.12149
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 014AD
UT WOS:000309346500010
ER
PT J
AU Yang, JJ
Bellgowan, PSF
Martin, A
AF Yang, Jiongjiong
Bellgowan, Patrick S. F.
Martin, Alex
TI Threat, domain-specificity and the human amygdala
SO NEUROPSYCHOLOGIA
LA English
DT Article
DE Amygdala; fMRI; Object category; Faces; Affect
ID FACIAL EXPRESSIONS; EMOTION; FACES; ATTENTION; STIMULI; FEAR;
PREPAREDNESS; PERCEPTION; REDUCTION; KNOWLEDGE
AB It is well documented that the human amygdala responds strongly to human faces, especially when depicting negative emotions. The extent to which the amygdala also responds to other animate entities - as well as to inanimate objects - and how that response is modulated by the object's perceived affective valence and arousal value remains unclear. To address these issues, subjects performed a repetition detection task to photographs of negative, neutral, and positive faces, animals, and manipulable objects equated for emotional valence and arousal level. Both the left and right amygdala responded more to animate entities than manipulable objects, especially for negative objects (fearful faces, threatening animals, versus weapons) and to neutral stimuli (faces with neutral expressions, neutral animals, versus tools). Thus, in the absence of contextual cues, the human amygdala responds to threat associated with some object categories (animate things) but not others (weapons). Although failing to activate the amygdala, relative to viewing other manipulable objects, viewing weapons did elicit an enhanced response in dorsal stream regions linked to object action. Thus, our findings suggest two circuits underpinning an automatic response to threatening stimuli; an amygdala-based circuit for animate entities, and a cortex-based circuit for responding to manmade, manipulable objects. Published by Elsevier Ltd.
C1 [Yang, Jiongjiong; Bellgowan, Patrick S. F.; Martin, Alex] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
RP Martin, A (reprint author), Natl Inst Mental Hlth DIRP, NIH, Bldg 10,Room 4C-104,MSC-1366, Bethesda, MD 20892 USA.
EM alexmartin@mail.nih.gov
FU NIMH Intramural Research Program at the National Institutes of Health
FX This work was supported by the NIMH Intramural Research Program at the
National Institutes of Health.
NR 43
TC 15
Z9 15
U1 1
U2 7
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3932
J9 NEUROPSYCHOLOGIA
JI Neuropsychologia
PD SEP
PY 2012
VL 50
IS 11
BP 2566
EP 2572
DI 10.1016/j.neuropsychologia.2012.07.001
PG 7
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA 013QA
UT WOS:000309318700004
PM 22820342
ER
PT J
AU Taber, DR
Chriqui, JF
Perna, FM
Powell, LM
Chaloupka, FJ
AF Taber, Daniel R.
Chriqui, Jamie F.
Perna, Frank M.
Powell, Lisa M.
Chaloupka, Frank J.
TI Weight Status Among Adolescents in States That Govern Competitive Food
Nutrition Content
SO PEDIATRICS
LA English
DT Article
DE competitive foods; state laws; BMI; adolescent
ID SUGAR-SWEETENED BEVERAGES; US PUBLIC-SCHOOLS; ARKANSAS ACT 1220;
BODY-MASS INDEX; CHILDHOOD OBESITY; VENDING MACHINES; DIETARY-INTAKE;
CHILDREN; POLICY; IMPLEMENTATION
AB OBJECTIVES: To determine if state laws regulating nutrition content of foods and beverages sold outside of federal school meal programs ("competitive foods") are associated with lower adolescent weight gain. \\
METHODS: The Westlaw legal database identified state competitive food laws that were scored by using the Classification of Laws Associated with School Students criteria. States were classified as having strong, weak, or no competitive food laws in 2003 and 2006 based on law strength and comprehensiveness. Objective height and weight data were obtained from 6300 students in 40 states in fifth and eighth grade (2004 and 2007, respectively) within the Early Childhood Longitudinal Study-Kindergarten Class. General linear models estimated the association between baseline state laws (2003) and within-student changes in BMI, overweight status, and obesity status. Fixed-effect models estimated the association between law changes during follow-up (2003-2006) and within-student changes in BMI and weight status.
RESULTS: Students exposed to strong laws at baseline gained, on average, 0.25 fewer BMI units (95% confidence interval: -0.54, 0.03) and were less likely to remain overweight or obese over time than students in states with no laws. Students also gained fewer BMI units if exposed to consistently strong laws throughout follow-up (beta = -0.44, 95% confidence interval: -0.71, -0.18). Conversely, students exposed to weaker laws in 2006 than 2003 had similar BMI gain as those not exposed in either year.
CONCLUSIONS: Laws that regulate competitive food nutrition content may reduce adolescent BMI change if they are comprehensive, contain strong language, and are enacted across grade levels. Pediatrics 2012; 130: 437444
C1 [Taber, Daniel R.; Chriqui, Jamie F.; Powell, Lisa M.; Chaloupka, Frank J.] Univ Illinois, Ctr Hlth Policy, Inst Hlth Res & Policy, Chicago, IL 60608 USA.
[Chriqui, Jamie F.] Univ Illinois, Dept Polit Sci, Chicago, IL 60608 USA.
[Powell, Lisa M.; Chaloupka, Frank J.] Univ Illinois, Dept Econ, Chicago, IL 60608 USA.
[Perna, Frank M.] NCI, Hlth Behav Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Taber, DR (reprint author), Univ Illinois, Ctr Hlth Policy, Inst Hlth Res & Policy, 1747 W Roosevelt Rd, Chicago, IL 60608 USA.
EM dtaber@uic.edu
FU Robert Wood Johnson Foundation; National Heart, Lung, and Blood
Institute [R01HL096664]; National Cancer Institute [HHSN261201000350P,
HHSN261201100522P]; National Institutes of Health (NIH)
FX Support for this study was provided by the Robert Wood Johnson
Foundation to the Bridging the Gap Program at the University of Illinois
at Chicago (PI: Frank Chaloupka); grant number R01HL096664 from the
National Heart, Lung, and Blood Institute (PI: Lisa Powell); and
contracts HHSN261201000350P and HHSN261201100522P from the National
Cancer Institute to the University of Illinois at Chicago (PI: Jamie
Chriqui). The views expressed herein are solely those of the authors and
do not reflect the official views or positions of the Robert Wood
Johnson Foundation; the National Heart, Lung, and Blood Institute; the
National Cancer Institute; or the National Institutes of Health. Funded
by the National Institutes of Health (NIH).
NR 52
TC 44
Z9 45
U1 2
U2 20
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD SEP
PY 2012
VL 130
IS 3
BP 437
EP 444
DI 10.1542/peds.2011-3353
PG 8
WC Pediatrics
SC Pediatrics
GA 014XO
UT WOS:000309409300045
PM 22891223
ER
PT J
AU Hinton, CF
Neuspiel, DR
Gubernick, RS
Geleske, T
Healy, J
Kemper, AR
Lloyd-Puryear, MA
Saul, RA
Thompson, BH
Kaye, CI
AF Hinton, Cynthia F.
Neuspiel, Daniel R.
Gubernick, Ruth S.
Geleske, Timothy
Healy, Jill
Kemper, Alex R.
Lloyd-Puryear, Michele A.
Saul, Robert A.
Thompson, Barry H.
Kaye, Celia I.
TI Improving Newborn Screening Follow-up in Pediatric Practices: Quality
Improvement Innovation Network
SO PEDIATRICS
LA English
DT Article
DE newborn screening; quality of health care
AB OBJECTIVE: To implement a 6-month quality improvement project in 15 primary care pediatric practices to improve short-term newborn screening (NBS) follow-up.
METHODS: At the start of the project, each practice completed a survey to evaluate office systems related to NBS and completed a chart audit. Practice teams were provided information about NBS and trained in quality-improvement methods, and then implemented changes to improve care. Monthly chart audits over a 6-month period were completed to assess change.
RESULTS: At baseline, almost half of practices completed assessment of infants for NBS; after 6 months, 80% of practices completed assessment of all infants. Only 2 practices documented all in-range results and shared them with parents at baseline; by completion, 10 of 15 practices documented and shared in-range results for >= 70% of infants. Use of the American College of Medical Genetics ACTion sheets, a decision support tool, increased from 1 of 15 practices at baseline to 7 of 15 at completion.
CONCLUSIONS: Practices were successful in improving NBS processes, including assessment, documentation, and communication with families. Providers perceived no increase in provider time at first visit, 2- to 4-week visit, or during first contact with the family of an infant with an out-of-range result after implementation of improved processes. Primary care practices increased their use of decision support tools after the project. Pediatrics 2012;130:e669-e675
C1 [Kaye, Celia I.] Univ Colorado Sch Med, Aurora, CO 80045 USA.
[Hinton, Cynthia F.] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA USA.
[Neuspiel, Daniel R.] Levine Childrens Hosp Carolinas Med Ctr, Charlotte, NC USA.
[Gubernick, Ruth S.] RSG Consulting, Cherry Hill, NJ USA.
[Geleske, Timothy] N Arlington Pediat, Arlington Hts, IL USA.
[Healy, Jill] Amer Acad Pediat, Elk Grove Village, IL USA.
[Kemper, Alex R.] Duke Univ, Dept Pediat, Durham, NC 27706 USA.
[Kemper, Alex R.] Duke Univ, Duke Clin Res Inst, Durham, NC USA.
[Lloyd-Puryear, Michele A.] NIH, Off Rare Dis Res, Bethesda, MD 20892 USA.
[Saul, Robert A.] Greenwood Genet Ctr, Greenwood, SC 29646 USA.
[Thompson, Barry H.] Amer Coll Med Genet, Bethesda, MD USA.
RP Kaye, CI (reprint author), Univ Colorado Sch Med, Anschutz Med Campus,13001 E 17th Pl,Room E1330, Aurora, CO 80045 USA.
EM celia.kaye@ucdenver.edu
FU American College of Medical Genetics [U22MC03957]; American Academy of
Pediatrics
FX Supported in part through a cooperative agreement between the Maternal
and Child Health Bureau/Health Resources and Services Administration and
the American College of Medical Genetics, grant U22MC03957, and the
American Academy of Pediatrics.
NR 6
TC 1
Z9 1
U1 1
U2 4
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD SEP
PY 2012
VL 130
IS 3
BP E669
EP E675
DI 10.1542/peds.2011-2920
PG 7
WC Pediatrics
SC Pediatrics
GA 014XO
UT WOS:000309409300025
PM 22869832
ER
PT J
AU Shneider, BL
Magee, JC
Bezerra, JA
Haber, B
Karpen, SJ
Raghunathan, T
Rosenthal, P
Schwarz, K
Suchy, FJ
Kerkar, N
Turmelle, Y
Whitington, PF
Robuck, PR
Sokol, RJ
AF Shneider, Benjamin L.
Magee, John C.
Bezerra, Jorge A.
Haber, Barbara
Karpen, Saul J.
Raghunathan, Trivellore
Rosenthal, Philip
Schwarz, Kathleen
Suchy, Frederick J.
Kerkar, Nanda
Turmelle, Yumirle
Whitington, Peter F.
Robuck, Patricia R.
Sokol, Ronald J.
CA Childhood Liver Dis Res Educ Netwo
TI Efficacy of Fat-Soluble Vitamin Supplementation in Infants With Biliary
Atresia
SO PEDIATRICS
LA English
DT Article
DE cholestasis; nutrition; liver; vitamin deficiency
ID POLYETHYLENE GLYCOL-1000 SUCCINATE; CHRONIC CHILDHOOD CHOLESTASIS;
E-DEFICIENCY; LIVER-DISEASE; CYSTIC-FIBROSIS; K DEFICIENCY; CHILDREN;
ABSORPTION; 25-HYDROXYVITAMIN-D; MULTICENTER
AB OBJECTIVE: Cholestasis predisposes to fat-soluble vitamin (FSV) deficiencies. A liquid multiple FSV preparation made with tocopheryl polyethylene glycol-1000 succinate (TPGS) is frequently used in infants with biliary atresia (BA) because of ease of administration and presumed efficacy. In this prospective multicenter study, we assessed the prevalence of FSV deficiency in infants with BA who received this FSV/TPGS preparation.
METHODS: Infants received FSV/TPGS coadministered with additional vitamin K as routine clinical care in a randomized double-blinded, placebo-controlled trial of corticosteroid therapy after hepatoportoenterostomy (HPE) for BA (identifier NCT 00294684). Levels of FSV, retinol binding protein, total serum lipids, and total bilirubin (TB) were measured 1, 3, and 6 months after HPE.
RESULTS: Ninety-two infants with BA were enrolled in this study. Biochemical evidence of FSV insufficiency was common at all time points for vitamin A (29%-36% of patients), vitamin D (21%-37%), vitamin K (10%-22%), and vitamin E (16%-18%). Vitamin levels were inversely correlated with serum TB levels. Biochemical FSV insufficiency was much more common (15%-100% for the different vitamins) in infants whose TB was >= 2 mg/dL. At 3 and 6 months post HPE, only 3 of 24 and 0 of 23 infants, respectively, with TB >2 mg/dL were sufficient in all FSV.
CONCLUSIONS: Biochemical FSV insufficiency is commonly observed in infants with BA and persistent cholestasis despite administration of a TPGS containing liquid multiple FSV preparation. Individual vitamin supplementation and careful monitoring are warranted in infants with BA, especially those with TB >2 mg/dL. Pediatrics 2012;130:e607-e614
C1 [Shneider, Benjamin L.] Childrens Hosp Pittsburgh UPMC, Div Pediat Gastoenterol Hepatol & Nutr, Dept Pediat, Pittsburgh, PA 15224 USA.
[Magee, John C.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA.
[Raghunathan, Trivellore] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
[Bezerra, Jorge A.] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH USA.
[Haber, Barbara] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA.
[Karpen, Saul J.] Texas Childrens Hosp, Dept Pediat, Houston, TX 77030 USA.
[Rosenthal, Philip] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA.
[Schwarz, Kathleen] Johns Hopkins Univ, Dept Pediat, Baltimore, MD 21218 USA.
[Suchy, Frederick J.; Sokol, Ronald J.] Childrens Hosp Colorado, Aurora, CO USA.
[Suchy, Frederick J.; Sokol, Ronald J.] Univ Colorado Sch Med, Dept Pediat, Aurora, CO USA.
[Kerkar, Nanda] Mt Sinai Sch Med, Dept Pediat, New York, NY USA.
[Turmelle, Yumirle] Washington Univ, Dept Pediat, St Louis, MO 63130 USA.
[Whitington, Peter F.] Childrens Mem Hosp, Dept Pediat, Chicago, IL 60614 USA.
[Robuck, Patricia R.] NIDDKD, NIH, Bethesda, MD 20892 USA.
RP Shneider, BL (reprint author), Childrens Hosp Pittsburgh UPMC, Div Pediat Gastoenterol Hepatol & Nutr, Dept Pediat, 4401 Penn Ave, Pittsburgh, PA 15224 USA.
EM benjamin.shneider@chp.edu
FU National Center for Research Resources [5M01 RR00069, UL1RR025780,
UL1RR024153, UL1RR024134, UL1RR024131, UL1RR025005, UL1RR025741,
UL1RR029877, UL1RR026314, UL1RR024992]; National Institute of Diabetes,
Digestive and Kidney Diseases [DK 62453, DK 62497, DK 62481, DK 62470,
DK 62500, DK 62530, DK 62445, DK 62466, DK 62456, DK 62452, DK 62436];
National Institutes of Health (NIH)
FX This work was supported by the National Center for Research Resources
(5M01 RR00069 [Dr Sokol], UL1RR025780 [Colorado],
UL1RR024153[Pittsburgh], UL1RR024134 [Philadelphia], UL1RR024131 [San
Francisco], UL1RR025005 [Baltimore], UL1RR025741 [Chicago], UL1RR029877
[New York], UL1RR026314 [Cincinnati], UL1RR024992 [St. Louis]) and U01
grants from the National Institute of Diabetes, Digestive and Kidney
Diseases (DK 62453 [Dr Sokol], DK 62497 [Dr Bezerra], DK 62481 [Dr
Haber], DK 62470 [Dr Karpen], DK 62500 [Dr Robuck], DK 62530 [Dr
Schwarz], DK 62445 [Drs Suchy and Kerkar], DK 62466 [Dr Shneider], DK
62456 [Dr Magee], DK 62452 [Dr Turmelle], and DK 62436 [Dr Whitington]).
Funded by the National Institutes of Health (NIH).
NR 25
TC 21
Z9 22
U1 0
U2 7
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
EI 1098-4275
J9 PEDIATRICS
JI Pediatrics
PD SEP
PY 2012
VL 130
IS 3
BP E607
EP E614
DI 10.1542/peds.2011-1423
PG 8
WC Pediatrics
SC Pediatrics
GA 014XO
UT WOS:000309409300018
PM 22891232
ER
PT J
AU Insel, TR
AF Insel, Thomas R.
TI An Interview with Thomas R. Insel, MD
SO PSYCHIATRIC ANNALS
LA English
DT Editorial Material
C1 [Insel, Thomas R.] NIMH, Bethesda, MD 20892 USA.
[Insel, Thomas R.] NIH, Bethesda, MD 20892 USA.
RP Insel, TR (reprint author), NIMH, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 0048-5713
J9 PSYCHIAT ANN
JI Psychiatr. Ann.
PD SEP
PY 2012
VL 42
IS 9
BP 350
EP 351
PG 2
WC Psychiatry
SC Psychiatry
GA 014ZF
UT WOS:000309413800009
ER
PT J
AU Shafighi, M
Fathi, AR
Brun, C
Huemer, GM
Wirth, R
Hunger, R
Banic, A
Constantinescu, MA
AF Shafighi, Maziar
Fathi, Ali R.
Brun, Claudio
Huemer, Georg M.
Wirth, Raphael
Hunger, Robert
Banic, Andrej
Constantinescu, Mihai A.
TI Topical application of 17 beta-estradiol (E2) improves skin flap
survival through activation of endothelial nitric oxide synthase in rats
SO WOUND REPAIR AND REGENERATION
LA English
DT Article
ID ESTROGEN-RECEPTOR-ALPHA; GROWTH-FACTOR-BETA; CARDIOMYOCYTE APOPTOSIS;
ISCHEMIC NECROSIS; PROGENITOR CELLS; SEX-HORMONES; IN-VIVO; ESTRADIOL;
MODEL; ANGIOGENESIS
AB This study investigates the influence of 17 beta-estradiol (E2) on nitric oxide (NO) production in endothelial cell cultures and the effect of topical E2 on the survival of skin flap transplants in a rat model. Human umbilical vein endothelial cells were treated with three different E2 concentrations and nitrite (NO2) concentrations, as well as endothelial nitric oxide synthase (eNOS) protein expressions were analyzed. In vivo, random-pattern skin flaps were raised in female Wistar rats 14 days following ovariectomy and treated with placebo ointment (group 1), E2 as gel (group 2), and E2 via plaster (group 3). Flap perfusion, survival, and NO2 levels were measured on postoperative day 7. In vitro, E2 treatment increased NO2 concentration in cell supernatant and eNOS expression in cell lysates (p < 0.05). In vivo, E2 treated (gel and plaster groups) demonstrated significantly increased skin flap survival compared to the placebo group (p < 0.05). E2 plaster-treated animals exhibited higher NO2 blood levels than placebo (p < 0.05) paralleling the in vitro observations. E2 increases NO production in endothelial cells via eNOS activation. Topical E2 application can significantly increase survival of ischemically challenged skin flaps in a rat model and may augment wound healing in other ischemic situations via activation of NO production.
C1 [Shafighi, Maziar; Brun, Claudio; Wirth, Raphael; Banic, Andrej; Constantinescu, Mihai A.] Univ Hosp, Inselspital, Dept Plast Reconstruct & Hand Surg, CH-3010 Bern, Switzerland.
[Shafighi, Maziar; Brun, Claudio; Wirth, Raphael; Hunger, Robert; Banic, Andrej; Constantinescu, Mihai A.] Univ Bern, CH-3012 Bern, Switzerland.
[Fathi, Ali R.] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD USA.
[Huemer, Georg M.] Gen Hosp Linz, Sect Plast Surg, Linz, Austria.
[Hunger, Robert] Univ Hosp, Inselspital, Dept Dermatol, CH-3010 Bern, Switzerland.
RP Shafighi, M (reprint author), Univ Hosp, Inselspital, Dept Plast Reconstruct & Hand Surg, CH-3010 Bern, Switzerland.
EM maziar_shafighi@yahoo.com
NR 38
TC 3
Z9 7
U1 3
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1067-1927
J9 WOUND REPAIR REGEN
JI Wound Repair Regen.
PD SEP-OCT
PY 2012
VL 20
IS 5
BP 740
EP 747
DI 10.1111/j.1524-475X.2012.00816.x
PG 8
WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery
SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery
GA 008GI
UT WOS:000308945000273
PM 22805596
ER
PT J
AU Severinsen, K
Kraft, JF
Koldso, H
Vinberg, KA
Rothman, RB
Partilla, JS
Wiborg, O
Blough, B
Schiott, B
Sinning, S
AF Severinsen, Kasper
Kraft, Johan F.
Koldso, Heidi
Vinberg, Katrine A.
Rothman, Richard B.
Partilla, John S.
Wiborg, Ove
Blough, Bruce
Schiott, Birgit
Sinning, Steffen
TI Binding of the Amphetamine-like 1-Phenyl-piperazine to Monoamine
Transporters
SO ACS CHEMICAL NEUROSCIENCE
LA English
DT Article
DE Dopamine transporter; serotonin transporter; induced fit docking;
phenyl-piperazine; cocaine; LeuT
ID BIOGENIC-AMINE TRANSPORTERS; HUMAN SEROTONIN TRANSPORTER; POTENTIAL
TREATMENT AGENTS; DOPAMINE TRANSPORTER; FORCE-FIELD; NEUROTRANSMITTER
TRANSPORTERS; DOPAMINE/SEROTONIN RELEASERS; COCAINE; IDENTIFICATION;
ADDICTION
AB The human serotonin transporter (hSERT), the human dopamine transporter (hDAT), and the human norepinephrine transporter (hNET) facilitate the active uptake of the neurotransmitters serotonin, dopamine, and norepinephrine from the synaptic cleft. Drugs of abuse such as MDMA (streetname "ecstasy") and certain 1-phenyl-piperazine (PP) analogs such as 1-(3-chlorophenyl)-piperazine (mCPP) elicit their stimulatory effect by elevating the synaptic concentration of serotonin by blocking or reversing the normal transport activity of hSERT. Recent data suggest that certain analogs of PP may be able to counteract the addictive effect of cocaine. Little is still known about the precise mechanism by which MDMA and PP analogs function at hSERT, hDAT, and hNET and even less is known about the specific protein ligand interactions. In this study, we provide a comprehensive biochemical examination of a repertoire of PP analogs in hSERT, hDAT, and hNET. Combined with induced fit docking models and molecular dynamics simulations of PP and 1-(3-hydroxyphenyl)-piperazine (3-OH-PP) bound to hSERT and hDAT, we present detailed molecular insight into the promiscuous binding of PP analogs in the monoamine transporters. We find that PP analogs inhibit uptake as well as induce release in all three monoamine transporters. We also find that the selectivity of the PP analogs can be adjusted by carefully selecting substituents on the PP skeleton.
C1 [Kraft, Johan F.; Koldso, Heidi; Schiott, Birgit] Aarhus Univ, Dept Chem, Ctr Insoluble Prot Struct InSPIN, Interdisciplinary Nanosci Ctr iNANO, DK-8000 Aarhus C, Denmark.
[Severinsen, Kasper; Vinberg, Katrine A.; Wiborg, Ove; Sinning, Steffen] Aarhus Univ Hosp, Ctr Psychiat Res, Lab Mol Neurobiol, Risskov, Denmark.
[Blough, Bruce] Res Triangle Inst, Ctr Organ & Med Chem, Res Triangle Pk, NC 27709 USA.
[Rothman, Richard B.; Partilla, John S.] NIDA, Translat Pharmacol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Schiott, B (reprint author), Aarhus Univ, Dept Chem, Ctr Insoluble Prot Struct InSPIN, Interdisciplinary Nanosci Ctr iNANO, Langelandsgade 140, DK-8000 Aarhus C, Denmark.
EM birgit@chem.au.dk; steffen.sinning@cpf.au.dk
RI Schiott, Birgit/F-5067-2011;
OI Schiott, Birgit/0000-0001-9937-1562; Sinning,
Steffen/0000-0001-6971-6929
FU Lundbeck Foundation; Carlsberg Foundation; Novo Nordisk Foundation;
Danish Strategic Research Council; Danish National Research Foundation;
National Institute of Drug Abuse (USA) [DA12790]; Aarhus Graduate School
of Science (AGSoS); iNANOSchool; Intramural Research Program, National
Institute on Drug Abuse, NIH, DHHS, Baltimore, MD
FX The research was supported by grants from the Lundbeck, Carlsberg, and
Novo Nordisk Foundations, the Danish Strategic Research Council, the
Danish National Research Foundation, and the National Institute of Drug
Abuse (USA, Grant DA12790). Computations were possible through
allocations of time at the Centre for Scientific Computing, Aarhus. We
thank Aarhus Graduate School of Science (AGSoS) and iNANOSchool for
financial support. Portions of this work were supported by the
Intramural Research Program, National Institute on Drug Abuse, NIH,
DHHS, Baltimore, MD.
NR 53
TC 19
Z9 19
U1 1
U2 9
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1948-7193
J9 ACS CHEM NEUROSCI
JI ACS Chem. Neurosci.
PD SEP
PY 2012
VL 3
IS 9
BP 693
EP 705
DI 10.1021/cn300040f
PG 13
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences
& Neurology
GA 009HI
UT WOS:000309016500008
PM 23019496
ER
PT J
AU Yekkirala, AS
Banks, ML
Lunzer, MM
Negus, SS
Rice, KC
Portoghese, PS
AF Yekkirala, Ajay S.
Banks, Matthew L.
Lunzer, Mary M.
Negus, Stevens S.
Rice, Kenner C.
Portoghese, Philip S.
TI Clinically Employed Opioid Analgesics Produce Antinociception via
mu-delta Opioid Receptor Heteromers in Rhesus Monkeys
SO ACS CHEMICAL NEUROSCIENCE
LA English
DT Article
DE Analgesics; Allosterism; GPCR heteromers; opioid antagonism; primates
ID PHARMACOLOGICAL CHARACTERIZATION; NARCOTIC ANTAGONISTS; AGONIST SNC80;
MORPHINE; MICE; DEPENDENCE; CLONING; EXPRESSION; TOLERANCE;
HETERODIMERIZATION
AB Morphine and related drugs are widely employed as analgesics despite the side effects associated with their use. Although morphine is thought to mediate analgesia through mu opioid receptors, delta opioid receptors have been implicated in mediating some side effects such as tolerance and dependence. Here we present evidence in rhesus monkeys that morphine, fentanyl, and possibly methadone selectively activate mu-delta heteromers to produce antinociception that is potently antagonized by the delta opioid receptor antagonist, naltrindole (NTI). Studies with HEK293 cells expressing mu-delta heteromeric opioid receptors exhibit a similar antagonism profile of receptor activation in the presence of NTI. In mice, morphine was potently inhibited by naltrindole when administered intrathecally, but not intracerebroventricularly, suggesting the possible involvement of mu-delta heteromers in the spinal cord of rodents. Taken together, these results strongly suggest that, in primates, mu-delta heteromers are allosterically coupled and mediate the antinociceptive effects of three clinically employed opioid analgesics that have been traditionally viewed as mu-selective. Given the known involvement of delta receptors in morphine tolerance and dependence, our results implicate mu-delta heteromers in mediating both antinociception and these side effects in primates. These results open the door for further investigation in humans.
C1 [Yekkirala, Ajay S.; Lunzer, Mary M.; Portoghese, Philip S.] Univ Minnesota, Coll Pharm, Dept Med Chem, Minneapolis, MN 55455 USA.
[Yekkirala, Ajay S.; Portoghese, Philip S.] Univ Minnesota, Sch Med, Dept Pharmacol, Minneapolis, MN 55455 USA.
[Banks, Matthew L.; Negus, Stevens S.] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA.
[Rice, Kenner C.] NIDA, Chem Biol Res Branch, Bethesda, MD 20892 USA.
[Rice, Kenner C.] NIAAA, NIH, DHHS, Bethesda, MD 20892 USA.
RP Portoghese, PS (reprint author), Univ Minnesota, Coll Pharm, Dept Med Chem, 8-111 Weaver Densford Hall, Minneapolis, MN 55455 USA.
EM porto001@umn.edu
RI Banks, Matthew/K-4429-2014
OI Banks, Matthew/0000-0003-4949-5246
FU NIH from National Institute on Drug Abuse (NIDA) [R01-DA01533,
R01-DA011460, T32-DA007027]; Intramural Research Programs of NIDA;
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
FX This work was supported by NIH Grants R01-DA01533, R01-DA011460 and
T32-DA007027 from the National Institute on Drug Abuse (NIDA). A portion
of this work was also supported by Intramural Research Programs of NIDA
and National Institute on Alcohol Abuse and Alcoholism (NIAAA).
NR 41
TC 12
Z9 12
U1 0
U2 7
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1948-7193
J9 ACS CHEM NEUROSCI
JI ACS Chem. Neurosci.
PD SEP
PY 2012
VL 3
IS 9
BP 720
EP 727
DI 10.1021/cn300049m
PG 8
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences
& Neurology
GA 009HI
UT WOS:000309016500010
PM 23019498
ER
PT J
AU Baysan, M
Sarac, K
Chandrasekaran, R
AF Baysan, Mehmet
Sarac, Kamil
Chandrasekaran, R.
TI Polynomial time solution to minimum forwarding set problem in wireless
networks under disk coverage model
SO AD HOC NETWORKS
LA English
DT Article
DE Minimum forwarding set problem; Multi-point relay; Energy efficient
communication; Disk graphs
ID AD HOC NETWORKS; APPROXIMATION ALGORITHMS; GRAPHS; TOPOLOGY
AB In this paper, we consider a practical problem, called Minimum Forwarding Set Problem (MFSP), that emerges within the context of implementing (energy efficient) communication protocols for wireless ad hoc or sensor networks. For a given node v, MFSP asks for a minimum cardinality subset of 1-hop neighbors of v to cover v's 2-hop neighbors. MFSP problem is also known as multi-point relay (MPR) problem. It is shown to be an NP-complete problem for its general case that does not consider the coverage characteristics of wireless transmissions. In this paper, we present two polynomial time algorithms to solve the MFSP problem under disk coverage model for wireless transmissions. In our earlier work, we presented a polynomial time algorithm for this problem under unit disk coverage model. In the current work, we present several observations on the geometric characteristics of wireless transmissions under disk coverage model and build two alternative dynamic programming based solutions with different run time and space complexities to the problem. Disk coverage model is a more general model because it allows nodes to use arbitrary power levels for transmissions. As a result, the presented algorithms provide a more practical solution that can be used as a building block for energy efficient communication protocols designed for wireless ad hoc and sensor networks. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Sarac, Kamil; Chandrasekaran, R.] Univ Texas Dallas, Dept Comp Sci, Richardson, TX 75083 USA.
[Baysan, Mehmet] NINDS, Neurooncol Branch, NCI, NIH, Bethesda, MD 20892 USA.
RP Sarac, K (reprint author), Univ Texas Dallas, Dept Comp Sci, Richardson, TX 75083 USA.
EM mehmet.baysan@nih.gov; ksarac@utdallas.edu; chandra@utdallas.edu
NR 34
TC 2
Z9 2
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1570-8705
J9 AD HOC NETW
JI Ad Hoc Netw.
PD SEP
PY 2012
VL 10
IS 7
BP 1253
EP 1266
DI 10.1016/j.adhoc.2012.03.009
PG 14
WC Computer Science, Information Systems; Telecommunications
SC Computer Science; Telecommunications
GA 984RQ
UT WOS:000307209600007
ER
PT J
AU Yildirim, E
Carey, MA
Card, JW
Dietrich, A
Flake, GP
Zhang, YP
Bradbury, JA
Rebolloso, Y
Germolec, DR
Morgan, DL
Zeldin, DC
Birnbaumer, L
AF Yildirim, Eda
Carey, Michelle A.
Card, Jeffrey W.
Dietrich, Alexander
Flake, Gordon P.
Zhang, Yingpei
Bradbury, J. Alyce
Rebolloso, Yvette
Germolec, Dori R.
Morgan, Daniel L.
Zeldin, Darryl C.
Birnbaumer, Lutz
TI Severely blunted allergen-induced pulmonary Th2 cell response and lung
hyperresponsiveness in type 1 transient receptor potential
channel-deficient mice
SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
LA English
DT Article
DE calcium entry; transient receptor potential; cation channel;
store-operated channel; allergy
ID CAPACITATIVE CA2+ ENTRY; TRPC CHANNELS; T-CELL; ENDOTHELIAL-CELLS;
MICROVASCULAR PERMEABILITY; ENDOPLASMIC-RETICULUM; INTERFERON-GAMMA;
AIRWAY RESPONSE; TRPC1(-/-) MICE; ACTIVATION
AB Yildirim E, Carey MA, Card JW, Dietrich A, Flake GP, Zhang Y, Bradbury JA, Rebolloso Y, Germolec DR, Morgan DL, Zeldin DC, Birnbaumer L. Severely blunted allergen-induced pulmonary Th2 cell response and lung hyperresponsiveness in type 1 transient receptor potential channel-deficient mice. Am J Physiol Lung Cell Mol Physiol 303: L539-L549, 2012. First published July 13, 2012; doi:10.1152/ajplung.00389.2011.-Transient receptor potential channels (TRPCs) are widely expressed and regulate Ca2+ entry in the cells that participate in the pathophysiology of airway hyperreactivity, inflammation, and remodeling. In vitro studies point to a role for TRPC1-mediated Ca2+ signaling in several of these cell types; however, physiological evidence is lacking. Here we identify TRPC1 signaling as proinflammatory and a regulator of lung hyperresponsiveness during allergen-induced pulmonary response. TRPC1-deficient (Trpc1(-/-)) mice are hyposensitive to methacholine challenge and have significantly reduced allergen-induced pulmonary leukocyte infiltration coupled with an attenuated T helper type 2 (Th2) cell response. Upon in vitro allergen exposure, Trpc1(-/-) splenocytes show impaired proliferation and T cell receptor-induced IL-2 production. A high number of germinal centers in spleens of Trpc1(-/-) mice and elevated levels of immunoglobulins in their serum are indicative of dysregulated B cell function and homeostasis. Thus we propose that TRPC1 signaling is necessary in lymphocyte biology and in regulation of allergen-induced lung hyperresponsiveness, making TRPC1 a potential target for treatment of immune diseases and asthma.
C1 [Birnbaumer, Lutz] NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv,Intramural Res Program, Res Triangle Pk, NC 27709 USA.
[Dietrich, Alexander] Univ Calif Los Angeles, David Geffen Sch Med, Dept Anesthesiol, Los Angeles, CA 90095 USA.
RP Birnbaumer, L (reprint author), NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv,Intramural Res Program, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM birnbau1@niehs.nih.gov
RI Dietrich, Alexander/G-8619-2013;
OI Yildirim, Eda/0000-0002-4796-3854; Dietrich,
Alexander/0000-0002-1168-8707
FU National Institutes of Health: National Institute of Environmental
Health Sciences [ZO1-ES-101684, ZO1-ES-025043]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health: National Institute of Environmental
Health Sciences Grants ZO1-ES-101684 (L. Birnbaumer) and ZO1-ES-025043
(D. C. Zeldin). This research was conducted in part at the National
Institutes of Environmental Health Sciences Inhalation Facility under
contract to Alion Science and Technology.
NR 64
TC 8
Z9 9
U1 0
U2 4
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1040-0605
J9 AM J PHYSIOL-LUNG C
JI Am. J. Physiol.-Lung Cell. Mol. Physiol.
PD SEP
PY 2012
VL 303
IS 6
BP L539
EP L549
DI 10.1152/ajplung.00389.2011
PG 11
WC Physiology; Respiratory System
SC Physiology; Respiratory System
GA 010QN
UT WOS:000309109300007
PM 22797250
ER
PT J
AU Seidel, S
Neymeyer, H
Kahl, T
Roschel, T
Mutig, K
Flower, R
Schnermann, J
Bachmann, S
Paliege, A
AF Seidel, S.
Neymeyer, H.
Kahl, T.
Roeschel, T.
Mutig, K.
Flower, R.
Schnermann, J.
Bachmann, S.
Paliege, A.
TI Annexin A1 modulates macula densa function by inhibiting cyclooxygenase
2
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Article
DE annexin A1; juxtaglomerular apparatus; prostaglandins; glucocorticoid;
formyl-peptide receptors
ID FORMYL PEPTIDE RECEPTOR; NITRIC-OXIDE; CORTICAL CYCLOOXYGENASE-2;
PROSTAGLANDIN E-2; GENE-EXPRESSION; RENAL-CORTEX; RAT-KIDNEY; CELLS;
SECRETION; RELEASE
AB Seidel S, Neymeyer H, Kahl T, Roschel T, Mutig K, Flower R, Schnermann J, Bachmann S, Paliege A. Annexin A1 modulates macula densa function by inhibiting cyclooxygenase 2. Am J Physiol Renal Physiol 303: F845-F854, 2012. First published July 11, 2012; doi:10.1152/ajprenal.00704.2011.-Annexin A1 (ANXA1) exerts anti-inflammatory effects through multiple mechanisms including inhibition of prostaglandin synthesis. Once secreted, ANXA1 can bind to G protein-coupled formyl peptide receptors (Fpr) and activate diverse cellular signaling pathways. ANXA1 is known to be expressed in cells of the juxtaglomerular apparatus, but its relation to the expression of cyclooxygenase 2 (COX-2) in thick ascending limb and macula densa cells has not been elucidated. We hypothesized that ANXA1 regulates the biosynthesis of COX-2. ANXA1 abundance in rat kidney macula densa was extensively colocalized with COX-2 (95%). Furosemide, an established stimulus for COX-2 induction, caused enhanced expression of both ANXA1 and COX-2 with maintained colocalization (99%). In ANXA1-deficient mice, COX-2-positive cells were more numerous than in control mice (+107%; normalized to glomerular number; P < 0.05) and renin expression was increased (+566%; normalized to glomerular number; P < 0.05). Cultured macula densa cells transfected with full-length rat ANXA1 revealed downregulation of COX-2 mRNA (-59%; P < 0.05). Similarly, treatment with dexamethasone suppressed COX-2 mRNA in the cells (-49%; P < 0.05), while inducing ANXA1 mRNA (+56%; P < 0.05) and ANXA1 protein secretion. Inhibition of the ANXA-1 receptor Fpr1 with cyclosporin H blunted the effect of dexamethasone on COX-2 expression. These data show that ANXA1 exerts an inhibitory effect on COX-2 expression in the macula densa. ANXA1 may be a novel intrinsic modulator of renal juxtaglomerular regulation by inhibition of PGE2 synthesis.
C1 [Seidel, S.; Neymeyer, H.; Kahl, T.; Roeschel, T.; Mutig, K.; Bachmann, S.; Paliege, A.] Charite, Dept Anat, D-10115 Berlin, Germany.
[Flower, R.] Univ London, William Harvey Res Inst, Dept Biochem Pharmacol, London, England.
[Schnermann, J.] NIDDK, Bethesda, MD USA.
RP Paliege, A (reprint author), Charite, Dept Anat, Philippstr 12, D-10115 Berlin, Germany.
EM alexander.paliege@charite.de
FU Deutsche Forschungsgemeinschaft [FOR 667]
FX The Deutsche Forschungsgemeinschaft (FOR 667) supported these studies.
NR 48
TC 1
Z9 2
U1 0
U2 3
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1931-857X
J9 AM J PHYSIOL-RENAL
JI Am. J. Physiol.-Renal Physiol.
PD SEP
PY 2012
VL 303
IS 6
BP F845
EP F854
DI 10.1152/ajprenal.00704.2011
PG 10
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA 012RQ
UT WOS:000309254600007
PM 22791338
ER
PT J
AU Murphey-Corb, M
Rajakumar, P
Michael, H
Nyaundi, J
Didier, PJ
Reeve, AB
Mitsuya, H
Sarafianos, SG
Parniak, MA
AF Murphey-Corb, Michael
Rajakumar, Premeela
Michael, Heather
Nyaundi, Julia
Didier, Peter J.
Reeve, Aaron B.
Mitsuya, Hiroaki
Sarafianos, Stefan G.
Parniak, Michael A.
TI Response of Simian Immunodeficiency Virus to the Novel Nucleoside
Reverse Transcriptase Inhibitor 4 '-Ethynyl-2-Fluoro-2 '-Deoxyadenosine
In Vitro and In Vivo
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID RESISTANCE MUTATIONS; DRUG-RESISTANCE; POTENT ACTIVITY; MACAQUE; TYPE-1;
ASSOCIATION; MONOTHERAPY; INFECTION; THERAPY; FAILURE
AB Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) are essential components in first-line therapy for human immunodeficiency virus (HIV) infection. However, long-term treatment with existing NRTIs can be associated with significant toxic side effects and the emergence of drug-resistant strains. The identification of new NRTIs for the continued management of HIV-infected people therefore is paramount. In this report, we describe the response of a primary isolate of simian immunodeficiency virus (SIV) to 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) both in vitro and in vivo. EFdA was 3 orders of magnitude better than tenofovir (TFV), zidovudine (AZT), and emtricitabine (FTC) in blocking replication of SIV in monkey peripheral blood mononuclear cells (PBMCs) in vitro, and in a preliminary study using two Sly-infected macaques with advanced AIDS, it was highly effective at treating Sly infection and AIDS symptoms in vivo. Both animals had 3- to 4-log decreases in plasma virus burden within 1 week of EFdA therapy (0.4 mg/kg of body weight, delivered subcutaneously twice a day) that eventually became undetectable. Clinical signs of disease (diarrhea, weight loss, and poor activity) also resolved within the first month of treatment. No detectable clinical or pathological signs of drug toxicity were observed within 6 months of continuous therapy. Virus suppression was sustained until drug treatment was discontinued, at which time virus levels rebounded. Although the rebound virus contained the M184V/I mutation in the viral reverse transcriptase, EFdA was fully effective in maintaining suppression of mutant virus throughout the drug treatment period. These results suggest that expanded studies with EFdA are warranted.
C1 [Murphey-Corb, Michael; Michael, Heather; Nyaundi, Julia; Reeve, Aaron B.; Parniak, Michael A.] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA 15260 USA.
[Rajakumar, Premeela] New England Natl Primate Res Ctr, Southborough, MA USA.
[Didier, Peter J.] Tulane Natl Primate Res Ctr, Covington, LA USA.
[Sarafianos, Stefan G.] Univ Missouri, Dept Mol Microbiol, Columbia, MO USA.
[Mitsuya, Hiroaki] NIH, Expt Virol Sect, Bethesda, MD 20892 USA.
RP Murphey-Corb, M (reprint author), Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA 15260 USA.
EM mcorb@pitt.edu
OI Sarafianos, Stefan G/0000-0002-5840-154X
FU Public Health Service from National Institutes of Health [AI079801,
AI076119, AI055944]; Yamasa Corporation, Chiba, Japan
FX This work was supported by Public Health Service grants AI079801
(M.A.P.), AI076119 (S.G.S.), and AI055944 (M.M.C.) from the National
Institutes of Health and a grant-in-aid from Yamasa Corporation, Chiba,
Japan.
NR 25
TC 15
Z9 15
U1 0
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD SEP
PY 2012
VL 56
IS 9
BP 4707
EP 4712
DI 10.1128/AAC.00723-12
PG 6
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 994CN
UT WOS:000307908600019
PM 22713337
ER
PT J
AU Suzuki, S
Haruyama, N
Nishimura, F
Kulkarni, AB
AF Suzuki, Shigeki
Haruyama, Naoto
Nishimura, Fusanori
Kulkarni, Ashok B.
TI Dentin sialophosphoprotein and dentin matrix protein-1: Two highly
phosphorylated proteins in mineralized tissues
SO ARCHIVES OF ORAL BIOLOGY
LA English
DT Article
DE DSPP; DMP-1; Genetically engineered mouse models; Cell signalling
molecules; Astacin family proteinases
ID LINKED GLYCOPROTEINS SIBLINGS; BONE MORPHOGENETIC PROTEIN; IN-VIVO;
DENTINOGENESIS IMPERFECTA; GLYCOSAMINOGLYCAN CHAINS; DMP1-DEFICIENT
MICE; GENE-TRANSCRIPTION; PHOSPHOPHORYN DPP; SIALOPROTEIN; DMP1
AB Dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP-1) are highly phosphorylated proteins that belong to the family of small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and are essential for proper development of hard tissues such as teeth and bones. In order to understand how they contribute to tissue organization, DSPP and DMP-1 have been analyzed for over a decade using both in vivo and in vitro techniques. Among the five SIBLINGs, the DSPP and DMP-1 genes are located next to each other and their gene and protein structures are most similar. In this review we examine the phenotypes of the genetically engineered mouse models of DSPP and DMP-1 and also introduce complementary in vitro studies into the molecular mechanisms underlying these phenotypes. DSPP affects the mineralization of dentin more profoundly than DMP-1. In contrast, DMP-1 significantly affects bone mineralization and importantly controls serum phosphate levels by regulating serum FGF-23 levels, whereas DSPP does not show any systemic effects. DMP-1 activates integrin signalling and is endocytosed into the cytoplasm whereupon it is translocated to the nucleus. In contrast, DSPP only activates integrin-dependent signalling. Thus it is now clear that both DSPP and DMP-1 contribute to hard tissue mineralization and the tissues affected by each are different presumably as a result of their different expression levels. In fact, in comparison with DMP-1, the functional analysis of cell signalling by DSPP remains relatively unexplored. (C) 2012 Elsevier LtdElsevier Ltd. All rights reserved.
C1 [Suzuki, Shigeki; Nishimura, Fusanori] Hiroshima Univ, Grad Sch Biomed Sci, Div Cervico Gnathostomatol, Dept Dent Sci Hlth Promot,Minami Ku, Hiroshima 7348553, Japan.
[Suzuki, Shigeki; Kulkarni, Ashok B.] Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
[Haruyama, Naoto] Tokyo Med & Dent Univ, Sect Maxillofacial Orthognath, Dept Maxillofacial Reconstruct & Funct,Bunkyo Ku, Div Maxillofacial Neck Reconstruct,Grad Sch, Tokyo 1138549, Japan.
[Haruyama, Naoto] Tokyo Med & Dent Univ, GCOE Program, Int Res Ctr Mol Sci Tooth & Bone Dis, Bunkyo Ku, Tokyo 1138549, Japan.
RP Suzuki, S (reprint author), Hiroshima Univ, Grad Sch Biomed Sci, Div Cervico Gnathostomatol, Dept Dent Sci Hlth Promot,Minami Ku, 1-2-3 Kasumi, Hiroshima 7348553, Japan.
EM suzukis@hiroshima-u.ac.jp
RI Haruyama, Naoto/D-1993-2011
OI Haruyama, Naoto/0000-0001-6225-5816
FU Intramural NIH HHS [Z01 DE000698-10]
NR 85
TC 27
Z9 28
U1 2
U2 21
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0003-9969
J9 ARCH ORAL BIOL
JI Arch. Oral Biol.
PD SEP
PY 2012
VL 57
IS 9
BP 1165
EP 1175
DI 10.1016/j.archoralbio.2012.03.005
PG 11
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 008RS
UT WOS:000308974800003
PM 22534175
ER
PT J
AU Cifani, C
Di Bonaventura, MVM
Ubaldi, M
Rice, KC
Ciccocioppo, R
Massi, M
AF Cifani, C.
Di Bonaventura, M. V. Micioni
Ubaldi, M.
Rice, K. C.
Ciccocioppo, R.
Massi, M.
TI ROLE OF CRF SYSTEM IN A MODEL OF BINGE EATING IN FEMALE RATS
SO BEHAVIOURAL PHARMACOLOGY
LA English
DT Meeting Abstract
CT European-Behavioural-Pharmacology-Society Workshop on Eating Behaviour
and Obesity
CY SEP 07-09, 2012
CL Lecce, ITALY
SP European Behav Pharmacol Soc
C1 [Cifani, C.; Di Bonaventura, M. V. Micioni; Ubaldi, M.; Ciccocioppo, R.; Massi, M.] Univ Camerino, Sch Pharm, I-62032 Camerino, Italy.
[Rice, K. C.] NIDA, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0955-8810
J9 BEHAV PHARMACOL
JI Behav. Pharmacol.
PD SEP
PY 2012
VL 23
IS 5-6
BP 629
EP 629
PG 1
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA 985EL
UT WOS:000307246100034
ER
PT J
AU Shaham, Y
AF Shaham, Y.
TI THE USE OF THE REINSTATEMENT MODEL TO STUDY THE NEUROBIOLOGY OF RELAPSE
TO FOOD SEEKING DURING DIETING
SO BEHAVIOURAL PHARMACOLOGY
LA English
DT Meeting Abstract
CT European-Behavioural-Pharmacology-Society Workshop on Eating Behaviour
and Obesity
CY SEP 07-09, 2012
CL Lecce, ITALY
SP European Behav Pharmacol Soc
C1 [Shaham, Y.] Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0955-8810
J9 BEHAV PHARMACOL
JI Behav. Pharmacol.
PD SEP
PY 2012
VL 23
IS 5-6
BP 629
EP 629
PG 1
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA 985EL
UT WOS:000307246100032
ER
PT J
AU Stokes, W
McFarland, R
Kulpa-Eddy, J
Gatewood, D
Levis, R
Halder, M
Pulle, G
Kojima, H
Casey, W
Gaydamaka, A
Miller, T
Brown, K
Lewis, C
Chapsal, JM
Bruckner, L
Gairola, S
Kamphuis, E
Rupprecht, CE
Wunderli, P
McElhinney, L
De Mattia, F
Gamoh, K
Hill, R
Reed, D
Doelling, V
Johnson, N
Allen, D
Rinckel, L
Jones, B
AF Stokes, William
McFarland, Richard
Kulpa-Eddy, Jodie
Gatewood, Donna
Levis, Robin
Halder, Marlies
Pulle, Gayle
Kojima, Hajime
Casey, Warren
Gaydamaka, Alexander
Miller, Timothy
Brown, Karen
Lewis, Charles
Chapsal, Jean-Michel
Bruckner, Lukas
Gairola, Sunil
Kamphuis, Elisabeth
Rupprecht, Charles E.
Wunderli, Peter
McElhinney, Lorraine
De Mattia, Fabrizio
Gamoh, Koichiro
Hill, Richard
Reed, David
Doelling, Vivian
Johnson, Nelson
Allen, David
Rinckel, Lori
Jones, Brett
TI Report on the international workshop on alternative methods for human
and veterinary rabies vaccine testing: State of the science and planning
the way forward
SO BIOLOGICALS
LA English
DT Article
DE Rabies vaccines; Potency; Replacement; Refinement; Reduction;
Implementation; In vitro
ID MONOCLONAL-ANTIBODY; ANTIGENIC PROPERTIES; POTENCY TEST; ANIMAL USE;
GLYCOPROTEIN; VIRUS; ELISA; CHALLENGE; MICE
AB Potency testing of most human and veterinary rabies vaccines requires vaccination of mice followed by a challenge test using an intracerebral injection of live rabies virus. NICEATM, ICCVAM, and their international partners organized a workshop to review the availability and validation status of alternative methods that might reduce, refine, or replace the use of animals for rabies vaccine potency testing, and to identify research and development efforts to further advance alternative methods. Workshop participants agreed that general anesthesia should be used for intracerebral virus injections and that humane endpoints should be used routinely as the basis for euthanizing animals when conducting the mouse rabies challenge test. Workshop participants recommended as a near-term priority replacement of the mouse challenge with a test validated to ensure potency, such as the mouse antibody serum neutralization test for adjuvanted veterinary rabies vaccines for which an international collaborative study was recently completed. The workshop recommended that an in vitro antigen quantification test should be a high priority for product-specific validation of human and non-adjuvanted veterinary rabies vaccines. Finally, workshop participants recommended greater international cooperation to expedite development, validation, regulatory acceptance, and implementation of alternative test methods for rabies vaccine potency testing.
C1 [Stokes, William; Casey, Warren] NIEHS, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, Div Natl Toxicol Program,NIH, Res Triangle Pk, NC 27709 USA.
[McFarland, Richard; Levis, Robin] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA.
[Kulpa-Eddy, Jodie] US Anim & Plant Hlth Inspect Serv, USDA, Vet Serv, Riverdale, MD 20737 USA.
[Gatewood, Donna; Lewis, Charles; Hill, Richard] USDA, Ctr Vet Biol, Ames, IA 50010 USA.
[Halder, Marlies] Commiss European Communities, Joint Res Ctr, Inst Hlth & Consumer Protect, European Union Reference Lab Alternat Anim Testin, I-21027 Ispra, Varese, Italy.
[Pulle, Gayle] Hlth Canada, Ctr Vaccine Evaluat, Ottawa, ON K1A 0L2, Canada.
[Kojima, Hajime] Natl Inst Hlth Sci, Japanese Ctr Validat Alternat Methods, Setagaya Ku, Tokyo 1585801, Japan.
[Gaydamaka, Alexander] Inst Anim Hlth, Washington, DC USA.
[Miller, Timothy] Benchmark Biolabs, Lincoln, NE 68528 USA.
[Brown, Karen] Pair ODocs Consultants, Parkville, MO 64152 USA.
[Chapsal, Jean-Michel] Sanofi Pasteur, Lyon, France.
[Bruckner, Lukas] Inst Viruskrankheiten & Immunprophylaxe, CH-3147 Mittelhausern, Switzerland.
[Gairola, Sunil] Serum Inst India Ltd, Pune 411028, Maharashtra, India.
[Kamphuis, Elisabeth] Paul Ehrlich Inst, D-63225 Langen, Germany.
[Rupprecht, Charles E.] Ctr Dis Control & Prevent, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30329 USA.
[McElhinney, Lorraine] Anim Hlth & Vet Labs Agcy, Weybridge CH64 7TE, Surrey, England.
[De Mattia, Fabrizio] MSD Anim Hlth, NL-5830 AA Boxmeer, Netherlands.
[Gamoh, Koichiro] Minist Agr, Natl Vet Assay Lab, Kokubunji, Tokyo, Japan.
[Reed, David] D E Reed & Associates, Chanhassen, MN 55317 USA.
[Doelling, Vivian; Johnson, Nelson; Allen, David; Rinckel, Lori; Jones, Brett] Integrated Lab Syst Inc, Morrisville, NC 27560 USA.
RP Stokes, W (reprint author), NIEHS, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, Div Natl Toxicol Program,NIH, POB 12233,MD K2-16, Res Triangle Pk, NC 27709 USA.
EM stokes@niehs.nih.gov
RI McElhinney, Lorraine/C-7997-2011; APHA, Staff publications/E-6082-2010
OI McElhinney, Lorraine/0000-0002-6022-348X;
FU International Cooperation on Alternative Test Method (ICATM);
NICEATM-ICCVAM; European Union Reference Laboratory for Alternatives to
Animal Testing (EURL ECVAM); Health Canada; Japanese Center for the
Validation of Alternative Methods (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 Rabies 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
contributions to breakout group discussions and workshop proceedings.
Participating national/international validation organizations from the
International Cooperation on Alternative Test Method (ICATM) are also
gratefully acknowledged for their scientific contributions and financial
support, including NICEATM-ICCVAM, the European Union Reference
Laboratory for Alternatives to Animal Testing (EURL ECVAM), Health
Canada, and the Japanese Center for the Validation of Alternative
Methods (JaCVAM). Finally, the authors gratefully acknowledge Dr.
Rajendra Chhabra and Dr. Michael Humble from the National Institute of
Environmental Health Sciences, National Institutes of Health, USA for
their review of the manuscript.
NR 48
TC 13
Z9 13
U1 0
U2 17
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 2012
VL 40
IS 5
BP 369
EP 381
DI 10.1016/j.biologicals.2012.07.005
PG 13
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Pharmacology & Pharmacy
GA 010IB
UT WOS:000309087000008
PM 22884673
ER
PT J
AU Patrone, D
Resnik, D
Chin, L
AF Patrone, Daniel
Resnik, David
Chin, Lisa
TI BIOSECURITY AND THE REVIEW AND PUBLICATION OF DUAL-USE RESEARCH OF
CONCERN
SO BIOSECURITY AND BIOTERRORISM-BIODEFENSE STRATEGY PRACTICE AND SCIENCE
LA English
DT Review
ID JOURNALS; POLICIES; SCIENCE; FLU
AB Dual-use research of concern (DURC) is scientific research with significant potential for generating information that could be used to harm national security, the public health, or the environment. Editors responsible for journal policies and publication decisions play a vital role in ensuring that effective safeguards exist to cope with the risks of publishing scientific research with dual-use implications. We conducted an online survey of 127 chief editors of life science journals in 27 countries to examine their attitudes toward and experience with the review and publication of dual-use research of concern. Very few editors (11) had experience with biosecurity review, and no editor in our study reported having ever refused a submission on biosecurity grounds. Most respondents (74.8%) agreed that editors have a responsibility to consider biosecurity risks during the review process, but little consensus existed among editors on how to handle specific issues in the review and publication of research with potential dual-use implications. More work is needed to establish consensus on standards for the review and publication of dual-use research of concern in life science journals.
C1 [Patrone, Daniel] SUNY Coll Oneonta, Broome Community Coll, Dept Philosophy, Binghamton, NY USA.
[Resnik, David] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
[Chin, Lisa] Univ London, Int Programmes, Dept Publ Hlth, London, England.
RP Patrone, D (reprint author), SUNY Coll Oneonta, Dept Philosophy, 325 Fitzelle SUNY Oneonta, Oneonta, NY 13820 USA.
EM dpatrone@gmail.com
NR 29
TC 6
Z9 6
U1 0
U2 9
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1538-7135
J9 BIOSECUR BIOTERROR
JI Biosecur. Bioterror.
PD SEP
PY 2012
VL 10
IS 3
BP 290
EP 298
DI 10.1089/bsp.2012.0011
PG 9
WC Public, Environmental & Occupational Health; International Relations
SC Public, Environmental & Occupational Health; International Relations
GA 006EY
UT WOS:000308803500013
PM 22871221
ER
PT J
AU Brittain, EH
Fay, MP
Follmann, DA
AF Brittain, Erica H.
Fay, Michael P.
Follmann, Dean A.
TI A valid formulation of the analysis of noninferiority trials under
random effects meta-analysis
SO BIOSTATISTICS
LA English
DT Article
DE Active control trial; Clinical trial; Meta-analysis; Noninferiority
trial; Random effects; Synthesis method
ID NON-INFERIORITY TRIALS; DESIGN; ISSUES
AB A noninferiority (NI) trial is sometimes employed to show efficacy of a new treatment when it is unethical to randomize current patients to placebo because of the established efficacy of a standard treatment. Under this framework, if the NI trial determines that the treatment advantage of the standard to the new drug (i.e. S-N) is less than the historic advantage of the standard to placebo (S-P), then the efficacy of the new treatment (N-P) is established indirectly. We explicitly combine information from the NI trial with estimates from a random effects model, allowing study-to-study variability in k historic trials. Existing methods under random effects, such as the synthesis method, fail to account for the variability of the true standard versus placebo effect in the NI trial. Our method effectively uses a prediction interval for the missing standard versus placebo effect rather than a confidence interval of the mean. The consequences are to increase the variance of the synthesis method by incorporating a prediction variance term and to approximate the null distribution of the new statistic with a t with k-1 degrees of freedom instead of the standard normal. Thus, it is harder to conclude NI of the new to (predicted) placebo, compared with traditional methods, especially when k is small or when between study variability is large. When the between study variances are nonzero, we demonstrate substantial Type I error rate inflation with conventional approaches; simulations suggest that the new procedure has only modest inflation, and it is very conservative when between study variances are zero. An example is used to illustrate practical issues.
C1 [Brittain, Erica H.; Fay, Michael P.; Follmann, Dean A.] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA.
RP Brittain, EH (reprint author), NIAID, Biostat Res Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM ebrittain@niaid.nih.gov
OI Fay, Michael P./0000-0002-8643-9625
NR 15
TC 13
Z9 13
U1 2
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1465-4644
J9 BIOSTATISTICS
JI Biostatistics
PD SEP
PY 2012
VL 13
IS 4
BP 637
EP 649
DI 10.1093/biostatistics/kxs006
PG 13
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA 007JY
UT WOS:000308885800006
PM 22467938
ER
PT J
AU Li, Y
Graubard, BI
AF Li, Yan
Graubard, Barry I.
TI Pseudo semiparametric maximum likelihood estimation exploiting gene
environment independence for population-based case-control studies with
complex samples
SO BIOSTATISTICS
LA English
DT Article
DE Hardy-Weinberg equilibrium; Population weights; Selection probability;
Stratified multistage cluster sampling; Taylor linearization
ID INFERENCE
AB Advances in human genetics have led to epidemiological investigations not only of the effects of genes alone but also of gene-environment (G-E) interaction. A widely accepted design strategy in the study of how G-E relate to disease risks is the population-based case-control study (PBCCS). For simple random samples, semiparametric methods for testing G-E have been developed by Chatterjee and Carroll in 2005. The use of complex sampling in PBCCS that involve differential probabilities of sample selection of cases and controls and possibly cluster sampling is becoming more common. Two complexities, weighting for selection probabilities and intracluster correlation of observations, are induced by the complex sampling. We develop pseudo-semiparametric maximum likelihood estimators (pseudo-SPMLE) that apply to PBCCS with complex sampling. We study the finite sample performance of the pseudo-SPMLE using simulations and illustrate the pseudo-SPMLE with a US case-control study of kidney cancer.
C1 [Li, Yan] Univ Texas Arlington, Dept Math, Arlington, TX 76001 USA.
[Graubard, Barry I.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Li, Y (reprint author), Univ Texas Arlington, Dept Math, Arlington, TX 76001 USA.
EM liyanna@uta.edu; graubarb@mail.nih.gov
FU NIH [UCA159424A]
FX The research was supported by NIH grant UCA159424A.
NR 23
TC 1
Z9 1
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1465-4644
J9 BIOSTATISTICS
JI Biostatistics
PD SEP
PY 2012
VL 13
IS 4
BP 711
EP 723
DI 10.1093/biostatistics/kxs008
PG 13
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA 007JY
UT WOS:000308885800011
PM 22522235
ER
PT J
AU Kley, RA
Serdaroglu-Oflazer, P
Leber, Y
Odgerel, Z
van der Ven, PFM
Olive, M
Ferrer, I
Onipe, A
Mihaylov, M
Bilbao, JM
Lee, HS
Hohfeld, J
Djinovic-Carugo, K
Kong, K
Tegenthoff, M
Peters, SA
Stenzel, W
Vorgerd, M
Goldfarb, LG
Furst, DO
AF Kley, Rudolf A.
Serdaroglu-Oflazer, Piraye
Leber, Yvonne
Odgerel, Zagaa
van der Ven, Peter F. M.
Olive, Montse
Ferrer, Isidro
Onipe, Adekunle
Mihaylov, Mariya
Bilbao, Juan M.
Lee, Hee S.
Hoehfeld, Joerg
Djinovic-Carugo, Kristina
Kong, Kester
Tegenthoff, Martin
Peters, Soeren A.
Stenzel, Werner
Vorgerd, Matthias
Goldfarb, Lev G.
Fuerst, Dieter O.
TI Pathophysiology of protein aggregation and extended phenotyping in
filaminopathy
SO BRAIN
LA English
DT Article
DE myofibrillar myopathy; filaminopathy; filamin C mutation;
immunoglobulin-like domain; limb-girdle myopathy
ID UBIQUITIN-PROTEASOME SYSTEM; MYOFIBRILLAR MYOPATHY; MUSCULAR-DYSTROPHY;
MUTANT UBIQUITIN; SKELETAL-MUSCLE; IN-VIVO; MOLECULAR CHAPERONES;
OXIDATIVE STRESS; STRUCTURAL BASIS; BINDING PROTEIN
AB Mutations in FLNC cause two distinct types of myopathy. Disease associated with mutations in filamin C rod domain leading to expression of a toxic protein presents with progressive proximal muscle weakness and shows focal destructive lesions of polymorphous aggregates containing desmin, myotilin and other proteins in the affected myofibres; these features correspond to the profile of myofibrillar myopathy. The second variant associated with mutations in the actin-binding domain of filamin C is characterized by weakness of distal muscles and morphologically by non-specific myopathic features. A frameshift mutation in the filamin C rod domain causing haploinsufficiency was also found responsible for distal myopathy with some myofibrillar changes but no protein aggregation typical of myofibrillar myopathies. Controversial data accumulating in the literature require re-evaluation and comparative analysis of phenotypes associated with the position of the FLNC mutation and investigation of the underlying disease mechanisms. This is relevant and necessary for the refinement of diagnostic criteria and developing therapeutic approaches. We identified a p.W2710X mutation in families originating from ethnically diverse populations and re-evaluated a family with a p. V930_T933del mutation. Analysis of the expanded database allows us to refine clinical and myopathological characteristics of myofibrillar myopathy caused by mutations in the rod domain of filamin C. Biophysical and biochemical studies indicate that certain pathogenic mutations in FLNC cause protein misfolding, which triggers aggregation of the mutant filamin C protein and subsequently involves several other proteins. Immunofluorescence analyses using markers for the ubiquitin-proteasome system and autophagy reveal that the affected muscle fibres react to protein aggregate formation with a highly increased expression of chaperones and proteins involved in proteasomal protein degradation and autophagy. However, there is a noticeably diminished efficiency of both the ubiquitin-proteasome system and autophagy that impairs the muscle capacity to prevent the formation or mediate the degradation of aggregates. Transfection studies of cultured muscle cells imitate events observed in the patient's affected muscle and therefore provide a helpful model for testing future therapeutic strategies.
C1 [Kley, Rudolf A.; Tegenthoff, Martin; Vorgerd, Matthias] Ruhr Univ Bochum, Dept Neurol, Univ Hosp Bergmannsheil, Neuromuscular Ctr Ruhrgebiet, D-44789 Bochum, Germany.
[Serdaroglu-Oflazer, Piraye] Istanbul Univ, Dept Neurol, Istanbul Fac Med, TR-34390 Istanbul, Turkey.
[Leber, Yvonne; van der Ven, Peter F. M.; Mihaylov, Mariya; Hoehfeld, Joerg; Fuerst, Dieter O.] Univ Bonn, Inst Cell Biol, Dept Mol Cell Biol, D-53121 Bonn, Germany.
[Odgerel, Zagaa; Lee, Hee S.; Goldfarb, Lev G.] NIH, Bethesda, MD 20892 USA.
[Olive, Montse; Ferrer, Isidro] IDIBELL Hosp Univ Bellvitge, Dept Pathol, Inst Neuropathol, Barcelona 08907, Spain.
[Olive, Montse; Ferrer, Isidro] CIBERNED, Barcelona 08907, Spain.
[Onipe, Adekunle; Djinovic-Carugo, Kristina] Univ Vienna, Max F Perutz Labs, Dept Struct & Computat Biol, A-1030 Vienna, Austria.
[Bilbao, Juan M.] Univ Toronto, Sunnybrook Med Ctr, Dept Pathol, Toronto, ON M4N 3M5, Canada.
[Djinovic-Carugo, Kristina] Univ Ljubljana, Dept Biochem, Fac Chem & Chem Technol, Ljubljana 1000, Slovenia.
[Kong, Kester] Univ Toronto, Toronto Western Hosp, Div Neurol, Dept Med, Toronto, ON M5T 1S8, Canada.
[Peters, Soeren A.] Ruhr Univ Bochum, Dept Radiol, Univ Hosp Bergmannsheil, D-44789 Bochum, Germany.
[Stenzel, Werner] Charite Univ Med Berlin, Dept Neuropathol, D-10117 Berlin, Germany.
RP Kley, RA (reprint author), Ruhr Univ Bochum, Dept Neurol, Univ Hosp Bergmannsheil, Neuromuscular Ctr Ruhrgebiet, Burkle de la Camp Pl 1, D-44789 Bochum, Germany.
EM rudolf.kley@rub.de
OI Olive, Montse/0000-0001-5727-0165
FU German Research foundation [KL 2487/1-1, FOR1228, FOR1352]; German
Ministry of Education and Research [01GM0887]; Ruhr-University Bochum
[FoRUM K042-09]; Spanish Instituto de Salud Carlos III [PI08-574];
Intramural Research Program of the National Institute of Neurological
Disorders and Stroke, NIH
FX The German Research foundation [KL 2487/1-1 to R. A. K., FOR1228 to
Y.H., M. V., D.O.F., FOR1352 to J.H., K.Dj.-C., D.O.F.]; the German
Ministry of Education and Research [01GM0887 to R. A. K., P.F.M.v.d.V.,
M. V., D.O.F.]; the Ruhr-University Bochum [FoRUM K042-09 to R. A. K.];
and the Spanish Instituto de Salud Carlos III [PI08-574 to M.O.]. This
research was supported in part by the Intramural Research Program of the
National Institute of Neurological Disorders and Stroke, NIH.
NR 79
TC 24
Z9 24
U1 1
U2 11
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
J9 BRAIN
JI Brain
PD SEP
PY 2012
VL 135
BP 2642
EP 2660
DI 10.1093/brain/aws200
PN 9
PG 19
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 007FG
UT WOS:000308873600008
PM 22961544
ER
PT J
AU Gotts, SJ
Simmons, WK
Milbury, LA
Wallace, GL
Cox, RW
Martin, A
AF Gotts, Stephen J.
Simmons, W. Kyle
Milbury, Lydia A.
Wallace, Gregory L.
Cox, Robert W.
Martin, Alex
TI Fractionation of social brain circuits in autism spectrum disorders
SO BRAIN
LA English
DT Article
DE autism spectrum disorders; functional connectivity; resting state
functional MRI; limbic system; cluster analysis
ID INTRINSIC FUNCTIONAL ARCHITECTURE; CEREBRAL-CORTEX; DIAGNOSTIC
INTERVIEW; DEFAULT NETWORK; NEURAL BASIS; CONNECTIVITY; FMRI; STATE;
COGNITION; AMYGDALA
AB Autism spectrum disorders are developmental disorders characterized by impairments in social and communication abilities and repetitive behaviours. Converging neuroscientific evidence has suggested that the neuropathology of autism spectrum disorders is widely distributed, involving impaired connectivity throughout the brain. Here, we evaluate the hypothesis that decreased connectivity in high-functioning adolescents with an autism spectrum disorder relative to typically developing adolescents is concentrated within domain-specific circuits that are specialized for social processing. Using a novel whole-brain connectivity approach in functional magnetic resonance imaging, we found that not only are decreases in connectivity most pronounced between regions of the social brain but also they are selective to connections between limbic-related brain regions involved in affective aspects of social processing from other parts of the social brain that support language and sensorimotor processes. This selective pattern was independently obtained for correlations with measures of social symptom severity, implying a fractionation of the social brain in autism spectrum disorders at the level of whole circuits.
C1 [Gotts, Stephen J.; Milbury, Lydia A.; Wallace, Gregory L.; Martin, Alex] NIMH, Sect Cognit Neuropsychol, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
[Simmons, W. Kyle] Laureate Inst Brain Res, Tulsa, OK 74136 USA.
RP Gotts, SJ (reprint author), NIMH, Sect Cognit Neuropsychol, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
EM gottss@mail.nih.gov
RI Gotts, Stephen/J-4842-2012; Simmons, William/K-8925-2015;
OI Simmons, William/0000-0002-0399-9003; Wallace,
Gregory/0000-0003-0329-5054
FU National Institute of Mental Health, NIH, Division of Intramural
Research
FX This study was supported by the National Institute of Mental Health,
NIH, Division of Intramural Research.
NR 96
TC 90
Z9 91
U1 7
U2 42
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
J9 BRAIN
JI Brain
PD SEP
PY 2012
VL 135
BP 2711
EP 2725
DI 10.1093/brain/aws160
PN 9
PG 15
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 007FG
UT WOS:000308873600013
PM 22791801
ER
PT J
AU Zhang, YJ
Granholm, AC
Huh, K
Shan, LF
Diaz-Ruiz, O
Malik, N
Olson, L
Hoffer, BJ
Lupica, CR
Hoffman, AF
Backman, CM
AF Zhang, YaJun
Granholm, Ann-Charlotte
Huh, Kyounghee
Shan, Lufei
Diaz-Ruiz, Oscar
Malik, Nasir
Olson, Lars
Hoffer, Barry J.
Lupica, Carl R.
Hoffman, Alexander F.
Baeckman, Cristina M.
TI PTEN deletion enhances survival, neurite outgrowth and function of
dopamine neuron grafts to MitoPark mice
SO BRAIN
LA English
DT Article
DE transplantation; substantia nigra; striatal innervation; Akt; mTOR
ID POSITRON-EMISSION-TOMOGRAPHY; SEVERE PARKINSONS-DISEASE; RAT MODEL; AXON
REGENERATION; RECEPTOR SUPERSENSITIVITY; MESENCEPHALIC GRAFTS;
NEUROTROPHIC FACTOR; TRANSPLANTATION; CELLS; STRIATUM
AB Clinical trials in Parkinson's disease have shown that transplants of embryonic mesencephalic dopamine neurons form new functional connections within the host striatum, but the therapeutic benefits have been highly variable. One obstacle has been poor survival and integration of grafted dopamine neurons. Activation of Akt, a serine/threonine kinase that promotes cell survival and growth, increases the ability of neurons to survive after injury and to regenerate lost neuronal connections. Because the lipid phosphatase, phosphatase and tensin homolog (PTEN) inhibits Akt, we generated a mouse with conditional knock-out of PTEN in dopamine neurons, leading to constitutive expression of Akt in these neurons. Ventral mesencephalic tissue from dopamine phosphatase and tensin homologue knock-out or control animals was then transplanted bilaterally into the dopamine depleted striata of MitoPark mice that express a parkinsonian phenotype because of severe respiratory chain dysfunction in dopamine neurons. After transplantation into MitoPark mice, PTEN-deficient dopamine neurons were less susceptible to cell death, and exhibited a more extensive pattern of fibre outgrowth compared to control grafts. Voltammetric measurements demonstrated that dopamine release and reuptake were significantly increased in the striata of animals receiving dopamine PTEN knock-out transplants. These animals also displayed enhanced spontaneous and drug-induced locomotor activity, relative to control transplanted MitoPark mice. Our results suggest that disinhibition of the Akt-signalling pathway may provide a valuable strategy to enhance survival, function and integration of grafted dopamine neurons within the host striatum and, more generally, to improve survival and integration of different forms of neural grafts.
C1 [Lupica, Carl R.; Hoffman, Alexander F.; Baeckman, Cristina M.] NIDA, Cellular Neurobiol Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Granholm, Ann-Charlotte] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA.
[Granholm, Ann-Charlotte] Med Univ S Carolina, Ctr Ageing, Charleston, SC 29425 USA.
[Olson, Lars] Karolinska Inst, Dept Neurosci, SE-17177 Stockholm, Sweden.
[Hoffer, Barry J.] Case Western Reserve, Sch Med, Dept Neurosurg, Cleveland, OH 44106 USA.
[Zhang, YaJun; Huh, Kyounghee; Shan, Lufei; Diaz-Ruiz, Oscar; Malik, Nasir; Baeckman, Cristina M.] NIDA, Integrat Neurosci Branch, Intramural Res Programme, NIH, Baltimore, MD 21224 USA.
RP Backman, CM (reprint author), NIDA, Cellular Neurobiol Branch, Intramural Res Program, NIH, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM cbackman@mail.nih.gov
RI backman, cristina/C-1276-2013; Hoffman, Alexander/H-3035-2012
OI Hoffman, Alexander/0000-0002-2676-0628
FU U.S. National Institutes of Health; National Institute on Drug Abuse
Intramural Research Program; Swedish Research Council, Swedish Brain
Power, the Karolinska Distinguished Professor Award
FX This work was supported by the U.S. National Institutes of Health, the
National Institute on Drug Abuse Intramural Research Program and The
Swedish Research Council, Swedish Brain Power, the Karolinska
Distinguished Professor Award.
NR 56
TC 15
Z9 15
U1 0
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
EI 1460-2156
J9 BRAIN
JI Brain
PD SEP
PY 2012
VL 135
BP 2736
EP 2749
DI 10.1093/brain/aws196
PN 9
PG 14
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 007FG
UT WOS:000308873600015
PM 22961549
ER
PT J
AU Johnson, JO
Gibbs, JR
Megarbane, A
Urtizberea, JA
Hernandez, DG
Foley, AR
Arepalli, S
Pandraud, A
Simon-Sanchez, J
Clayton, P
Reilly, MM
Muntoni, F
Abramzon, Y
Houlden, H
Singleton, AB
AF Johnson, Janel O.
Gibbs, J. Raphael
Megarbane, Andre
Urtizberea, J. Andoni
Hernandez, Dena G.
Foley, A. Reghan
Arepalli, Sampath
Pandraud, Amelie
Simon-Sanchez, Javier
Clayton, Peter
Reilly, Mary M.
Muntoni, Francesco
Abramzon, Yevgeniya
Houlden, Henry
Singleton, Andrew B.
TI Exome sequencing reveals riboflavin transporter mutations as a cause of
motor neuron disease
SO BRAIN
LA English
DT Article
DE motor neuron disease; ALS; riboflavin; BVVL; SLC52A2
ID VAN-LAERE-SYNDROME; DEAFNESS; PALSY
AB Brown-Vialetto-Van Laere syndrome was first described in 1894 as a rare neurodegenerative disorder characterized by progressive sensorineural deafness in combination with childhood amyotrophic lateral sclerosis. Mutations in the gene, SLC52A3 (formerly C20orf54), one of three known riboflavin transporter genes, have recently been shown to underlie a number of severe cases of Brown-Vialetto-Van Laere syndrome; however, cases and families with this disease exist that do not appear to be caused by SLC52A3 mutations. We used a combination of linkage and exome sequencing to identify the disease causing mutation in an extended Lebanese Brown-Vialetto-Van Laere kindred, whose affected members were negative for SLC52A3 mutations. We identified a novel mutation in a second member of the riboflavin transporter gene family (gene symbol: SLC52A2) as the cause of disease in this family. The same mutation was identified in one additional subject, from 44 screened. Within this group of 44 patients, we also identified two additional cases with SLC52A3 mutations, but none with mutations in the remaining member of this gene family, SLC52A1. We believe this strongly supports the notion that defective riboflavin transport plays an important role in Brown-Vialetto-Van Laere syndrome. Initial work has indicated that patients with SLC52A3 defects respond to riboflavin treatment clinically and biochemically. Clearly, this makes an excellent candidate therapy for the SLC52A2 mutation-positive patients identified here. Initial riboflavin treatment of one of these patients shows promising results.
C1 [Johnson, Janel O.; Gibbs, J. Raphael; Hernandez, Dena G.; Pandraud, Amelie; Reilly, Mary M.; Houlden, Henry] UCL, Inst Neurol, MRC, Dept Mol Neurosci,Ctr Neuromuscular Dis, London WC1N 3BG, England.
[Johnson, Janel O.; Gibbs, J. Raphael; Hernandez, Dena G.; Pandraud, Amelie; Reilly, Mary M.; Houlden, Henry] UCL, Inst Neurol, Reta Lila Weston Inst Neurol Studies, London WC1N 3BG, England.
[Johnson, Janel O.; Gibbs, J. Raphael; Hernandez, Dena G.; Arepalli, Sampath; Simon-Sanchez, Javier; Abramzon, Yevgeniya; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Urtizberea, J. Andoni] Hosp Marin, MPR, Praticien Hosp, F-64700 Hendaye, France.
[Foley, A. Reghan; Muntoni, Francesco] UCL, Inst Child Hlth, MRC, Ctr Neuromuscular Disorders, London WC1N 1EH, England.
[Foley, A. Reghan; Muntoni, Francesco] UCL, Inst Child Hlth, Dubowitz Neuromuscular Ctr, London WC1N 1EH, England.
[Foley, A. Reghan; Clayton, Peter; Muntoni, Francesco] Great Ormond St Hosp Sick Children, London WC1N 1EH, England.
[Clayton, Peter] UCL, Inst Child Hlth, Clin & Mol Genet Unit, London WC1N 1EH, England.
RP Houlden, H (reprint author), UCL, Inst Neurol, MRC, Dept Mol Neurosci,Ctr Neuromuscular Dis, Queen Sq, London WC1N 3BG, England.
EM h.houlden@ucl.ac.uk; singleta@mail.nih.gov
RI Clayton, Peter/C-1523-2008; Houlden, Henry/C-1532-2008; Singleton,
Andrew/C-3010-2009
OI Houlden, Henry/0000-0002-2866-7777;
FU National Institute of Neurological Disorders and Stroke; National
Institute on Ageing, National Institutes of Health, Department of Health
and Human Services [Z01 AG 000958-08]; MRC [G0802760]; Wellcome Trust;
NIHR UCLH/UCL Comprehensive Biomedical Research Centre; Great Ormond
Street Children's Charity
FX This work was supported, in part, by the Intramural Research Programs of
the National Institute of Neurological Disorders and Stroke and the
National Institute on Ageing, National Institutes of Health, Department
of Health and Human Services; project number Z01 AG 000958-08. We thank
the MRC (H.H. MRC fellowship G0802760 and MRC neuromuscular centre
grant) and the Wellcome Trust for financial support. A.R.F. is a
Muscular Dystrophy Campaign fellow. This study was supported by the NIHR
UCLH/UCL Comprehensive Biomedical Research Centre. F.M. is supported by
the Great Ormond Street Children's Charity.
NR 15
TC 39
Z9 40
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 2012
VL 135
BP 2875
EP 2882
DI 10.1093/brain/aws161
PN 9
PG 8
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 007FG
UT WOS:000308873600027
PM 22740598
ER
PT J
AU Guan, Z
Qin, J
Zhang, B
AF Guan, Zhong
Qin, Jing
Zhang, Biao
TI Information borrowing methods for covariate-adjusted ROC curve
SO CANADIAN JOURNAL OF STATISTICS-REVUE CANADIENNE DE STATISTIQUE
LA English
DT Article
DE Bootstrap; covariate-adjusted ROC curve; density ratio model; diagnostic
test; logistic regression model; semiparametric likelihood; sensitivity;
specificity; Primary 60G05; secondary 60G09; 60P10
ID GOODNESS-OF-FIT; OPERATING CHARACTERISTIC CURVES; BOOTSTRAP; MODEL
AB In medical diagnostic testing problems, the covariate adjusted receiver operating characteristic (ROC) curves have been discussed recently for achieving the best separation between disease and control. Due to various restrictions such as cost, the availability of patients, and ethical issues quite frequently only limited information is available. As a result, we are unlikely to have a large enough overall sample size to support reliable direct estimations of ROCs for all the underlying covariates of interest. For example, some genetic factors are less commonly observable compared with others. To get an accurate covariate adjusted ROC estimation, novel statistical methods are needed to effectively utilize the limited information. Therefore, it is desirable to use indirect estimates that borrow strength by employing values of the variables of interest from neighbouring covariates. In this paper we discuss two semiparametric exponential tilting models, where the density functions from different covariate levels share a common baseline density, and the parameters in the exponential tilting component reflect the difference among the covariates. With the proposed models, the estimated covariate adjusted ROC is much smoother and more efficient than the nonparametric counterpart without borrowing information from neighbouring covariates. A simulation study and a real data application are reported. The Canadian Journal of Statistics 40: 569587; 2012 (c) 2012 Statistical Society of Canada
C1 [Guan, Zhong] Indiana Univ, Dept Math Sci, South Bend, IN 46634 USA.
[Qin, Jing] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA.
[Zhang, Biao] Univ Toledo, Dept Math, Toledo, OH 43606 USA.
RP Guan, Z (reprint author), Indiana Univ, Dept Math Sci, South Bend, IN 46634 USA.
EM zguan@iusb.edu
NR 22
TC 0
Z9 0
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0319-5724
J9 CAN J STAT
JI Can. J. Stat.-Rev. Can. Stat.
PD SEP
PY 2012
VL 40
IS 3
BP 569
EP 587
DI 10.1002/cjs.11145
PG 19
WC Statistics & Probability
SC Mathematics
GA 992IR
UT WOS:000307769400009
ER
PT J
AU Menon, MP
Pittaluga, S
Jaffe, ES
AF Menon, Madhu P.
Pittaluga, Stefania
Jaffe, Elaine S.
TI The Histological and Biological Spectrum of Diffuse Large B-Cell
Lymphoma in the World Health Organization Classification
SO CANCER JOURNAL
LA English
DT Review
DE Diffuse large B-cell lymphoma; plasmablastic lymphoma; Burkitt lymphoma;
double-hit lymphoma; gray zone lymphoma; Hodgkin lymphoma; cutaneous
lymphoma; central nervous system; immunophenotyping
ID PYOTHORAX-ASSOCIATED LYMPHOMA; PRIMARY EFFUSION LYMPHOMA; GRAY ZONE
LYMPHOMA; HIV-SERONEGATIVE PATIENT; NERVOUS-SYSTEM LYMPHOMA; DA-EPOCH-R;
GENE-EXPRESSION; HODGKIN LYMPHOMA; CLINICOPATHOLOGICAL ENTITY;
PLASMABLASTIC LYMPHOMA
AB Diffuse large B-cell lymphomas (DLBCLs) are aggressive B-cell lymphomas that are clinically, pathologically, and genetically diverse, in part reflecting the functional diversity of the B-cell system. The focus in recent years has been toward incorporation of clinical features, morphology, immunohistochemistry, and ever evolving genetic data into the classification scheme. The 2008 World Health Organization classification reflects this complexity with the addition of several new entities and variants. The discovery of distinct subtypes by gene expression profiling heralded a new era with a focus on pathways of transformation as well as a promise of more targeted therapies, directed at specific pathways. Some DLBCLs exhibit unique clinical characteristics with a predilection for specific anatomic sites; the anatomic site often reflects underlying biological distinctions. Recently, the spectrum of Epstein-Barr virus (EBV) Ydriven B-cell proliferations in patients without iatrogenic or congenital immunosuppression has been better characterized; most of these occur in patients of advanced age and include Epstein-Barr virus (EBV) Ypositive large B-cell lymphoma of the elderly. Human herpesvirus 8 is involved in the pathogenesis of primary effusion lymphoma, which can present as a "solid variant." Two borderline categories were created; one deals with tumors at the interface between classic Hodgkin lymphoma and DLBCL. The second confronts the interface between Burkitt lymphoma and DLBCL, so-called "B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma" in the 2008 classification. Most cases harbor both MYC and BCL2 translocations and are highly aggressive. Another interesting entity is anaplastic lymphoma kinase-positive DLBCL, which renders itself potentially targetable by anaplastic lymphoma kinase inhibitors. Ongoing investigations at the genomic level, with both exome and whole-genome sequencing, are sure to reveal new pathways of transformation in the future.
C1 [Menon, Madhu P.; Pittaluga, Stefania; Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Jaffe, ES (reprint author), NIH, Bldg 10,Room 2B42,10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA.
EM elainejaffe@nih.gov
OI Jaffe, Elaine/0000-0003-4632-0301
FU Intramural NIH HHS [ZIA SC000550-31]
NR 118
TC 38
Z9 46
U1 1
U2 18
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1528-9117
J9 CANCER J
JI Cancer J.
PD SEP-OCT
PY 2012
VL 18
IS 5
BP 411
EP 420
DI 10.1097/PPO.0b013e31826aee97
PG 10
WC Oncology
SC Oncology
GA 012EP
UT WOS:000309218600006
PM 23006945
ER
PT J
AU Roschewski, M
Wilson, WH
AF Roschewski, Mark
Wilson, Wyndham H.
TI Lymphomatoid Granulomatosis
SO CANCER JOURNAL
LA English
DT Review
DE Lymphomatoid granulomatosis; LYG; Epstein-Barr virus; EBV
ID B-LYMPHOCYTES; RITUXIMAB
AB Lymphomatoid granulomatosis (LYG) is a very rare Epstein-Barr virus (EBV)-driven lymphoproliferative disease. The atypical lymphoid cells directly accumulate within affected tissues and clinically present in the form of infiltrative lesions. It is usually a progressive disorder that virtually always involves the lung and characteristically presents as bilateral pulmonary nodules. Other commonly affected organ systems include the skin, central nervous system, and kidneys. The rareness of LYG in conjunction with its nonspecific presentation contributes to delays in diagnosis in many situations. Pathologically, it is characterized by the presence of an angiocentric and angiodestructive accumulation of varying numbers of T cells with varying numbers of atypical clonal EBV-positive B cells in a polymorphous inflammatory background. It can be subclassified using a grading system based on the number of EBV-positive large B-cell malignant cells, which is critical in selecting appropriate management strategies. Lower-grade LYG occasionally undergoes spontaneous remission and is best managed with strategies designed to enhance the host's underlying immune system, whereas high-grade LYG is best managed by combination chemoimmunotherapy but has inferior outcomes. Lymphomatoid granulomatosis can lead to progressive pulmonary failure, central nervous system disease, or progression to overt EBV-positive lymphoma without appropriate recognition and management. Improvements in the modern understanding of the biology of LYG, particularly the precise role of EBV in its pathogenesis, offer promise in the development of improved management strategies.
C1 [Wilson, Wyndham H.] NCI, Lymphoma Therapeut Sect, Metab Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Roschewski, Mark] Walter Reed Natl Mil Med Ctr, Hematol Malignancy Sect, Bethesda, MD USA.
RP Wilson, WH (reprint author), NCI, Lymphoma Therapeut Sect, Metab Branch, Ctr Canc Res,NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM wilsonw@mail.nih.gov
OI Roschewski, Mark/0000-0003-0278-2635
FU NIH
FX All research support comes from the intramural research program of the
NIH.
NR 21
TC 24
Z9 27
U1 0
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1528-9117
J9 CANCER J
JI Cancer J.
PD SEP-OCT
PY 2012
VL 18
IS 5
BP 469
EP 474
DI 10.1097/PPO.0b013e31826c5e19
PG 6
WC Oncology
SC Oncology
GA 012EP
UT WOS:000309218600015
PM 23006954
ER
PT J
AU Raveh, A
Valitsky, M
Shani, L
Coorssen, JR
Blank, PS
Zimmerberg, J
Rahamimoff, R
AF Raveh, Adi
Valitsky, Michael
Shani, Liora
Coorssen, Jens R.
Blank, Paul S.
Zimmerberg, Joshua
Rahamimoff, Rami
TI Observations of calcium dynamics in cortical secretory vesicles
SO CELL CALCIUM
LA English
DT Article
DE Secretory vesicles; Calcium dynamics; Confocal microscopy; Fluctuation
analysis; Super-Poisson statistics
ID SEA-URCHIN EGGS; SYNAPTIC VESICLES; FLUORESCENT CALCIUM; TRIGGERED
EXOCYTOSIS; TRANSMITTER RELEASE; PHOTON STATISTICS; ELECTRIC ORGAN; CA2+
SIGNALS; ION CHANNELS; CELLS
AB Calcium (Ca2+) dynamics were evaluated in fluorescently labeled sea urchin secretory vesicles using confocal microscopy. 71% of the vesicles examined exhibited one or more transient increases in the fluorescence signal that was damped in time. The detection of transient increases in signal was dependent upon the affinity of the fluorescence indicator; the free Ca2+ concentration in the secretory vesicles was estimated to be in the range of similar to 10 to 100 mu M. Non-linear stochastic analysis revealed the presence of extra variance in the Ca2+ dependent fluorescence signal. This noise process increased linearly with the amplitude of the Ca2+ signal. Both the magnitude and spatial properties of this noise process were dependent upon the activity of vesicle p-type (Ca(nu)2.1) Ca2+ channels. Blocking the p-type Ca2+ channels with omega-agatoxin decreased signal variance, and altered the spatial noise pattern within the vesicle. These fluorescence signal properties are consistent with vesicle Ca2+ dynamics and not simply due to obvious physical properties such as gross movement artifacts or pH driven changes in Ca2+ indicator fluorescence. The results suggest that the free Ca2+ content of cortical secretory vesicles is dynamic; this property may modulate the exocytotic fusion process. Published by Elsevier Ltd.
C1 [Blank, Paul S.; Zimmerberg, Joshua] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD USA.
[Raveh, Adi; Valitsky, Michael; Shani, Liora; Rahamimoff, Rami] Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Physiol, IL-91010 Jerusalem, Israel.
[Raveh, Adi; Valitsky, Michael; Shani, Liora; Rahamimoff, Rami] Hebrew Univ Jerusalem, Hadassah Med Sch, Bernard Katz Minerva Ctr Cell Biophys, IL-91010 Jerusalem, Israel.
[Coorssen, Jens R.] Univ Western Sydney, Dept Mol Physiol, Sch Med, Campbelltown, NSW, Australia.
[Coorssen, Jens R.] Univ Western Sydney, Mol Med Res Grp, Campbelltown, NSW, Australia.
RP Blank, PS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD USA.
EM blankp@mail.nih.gov
FU NIH; Eunice Kennedy Shriver National Institute of Child Health and Human
Development; US-Israel Binational Science Foundation; Israeli Science
Foundation
FX We thank Drs. Halina Meiri, Sam Hess, Jonathan Epstein and Rea Ravin for
helpful discussions. We thank Ms. Nadia Meschetnik for her participation
in part of the experiments. This research was supported, in part, by the
Intramural Research Program of the NIH, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, a US-Israel Binational
Science Foundation Grant, and the Israeli Science Foundation.
NR 70
TC 3
Z9 4
U1 0
U2 7
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0143-4160
J9 CELL CALCIUM
JI Cell Calcium
PD SEP-OCT
PY 2012
VL 52
IS 3-4
SI SI
BP 217
EP 225
DI 10.1016/j.ceca.2012.06.009
PG 9
WC Cell Biology
SC Cell Biology
GA 013ME
UT WOS:000309308700005
PM 22831912
ER
PT J
AU Krishnan, S
Fernandez, GE
Sacks, DB
Prasadarao, NV
AF Krishnan, Subramanian
Fernandez, G. Esteban
Sacks, David B.
Prasadarao, Nemani V.
TI IQGAP1 mediates the disruption of adherens junctions to promote
Escherichia coli K1 invasion of brain endothelial cells
SO CELLULAR MICROBIOLOGY
LA English
DT Article
ID MEMBRANE PROTEIN-A; KINASE-C; CALMODULIN; CDC42; ACTIN; ADHESION;
RECEPTOR; PERMEABILITY; CYTOSKELETON; SALMONELLA
AB The transcellular entry of Escherichia coli K1 through human brain microvascular endothelial cells (HBMEC) is responsible for tight junction disruption, leading to brain oedema in neonatal meningitis. Previous studies demonstrated that outer membrane protein A (OmpA) of E.?coli K1 interacts with its receptor, Ecgp96, to induce PKC-a phosphorylation, adherens junction (AJ) disassembly (by dislodging beta-catenin from VE-cadherin), and remodelling of actin in HBMEC. We report here that IQGAP1 mediates beta-catenin dissociation from AJs to promote actin polymerization required for E.?coli K1 invasion of HBMEC. Overexpression of C-terminal truncated IQGAP1 (IQ?C) that cannot bind beta-catenin prevents both AJ disruption and E.?coli K1 entry. Of note, phospho-PKC-a interacts with the C-terminal portion of Ecgp96 as well as with VE-cadherin after IQGAP1-mediated AJ disassembly. HBMEC overexpressing either C-terminal truncated Ecgp96 (Ecgp96?200) or IQ?C upon infection with E.?coli showed no interaction ofphospho-PKC-a with Ecgp96. These data indicate that the binding of OmpA to Ecgp96 induces PKC-a phosphorylation and association of phospho-PKC-a with Ecgp96, and then signals IQGAP1 to detach beta-catenin from AJs. Subsequently, IQGAP1/beta-catenin bound actin translocates to the site of E.?coli K1 attachment to promote invasion.
C1 [Krishnan, Subramanian; Prasadarao, Nemani V.] Univ So Calif, Childrens Hosp Los Angeles, Sch Med, Div Infect Dis,Dept Pediat,Saban Res Inst, Los Angeles, CA 90027 USA.
[Fernandez, G. Esteban] Univ So Calif, Childrens Hosp Los Angeles, Sch Med, Cellular Imaging Core,Saban Res Inst, Los Angeles, CA 90027 USA.
[Sacks, David B.] NIH, Dept Lab Med, Bethesda, MD 20892 USA.
[Prasadarao, Nemani V.] Univ So Calif, Childrens Hosp Los Angeles, Sch Med, Dept Surg,Saban Res Inst, Los Angeles, CA 90027 USA.
RP Prasadarao, NV (reprint author), Univ So Calif, Childrens Hosp Los Angeles, Sch Med, Div Infect Dis,Dept Pediat,Saban Res Inst, Los Angeles, CA 90027 USA.
EM pnemani@chla.usc.edu
OI Sacks, David/0000-0003-3100-0735
FU NIH [AI40567, NS73115]; National Institutes of Health
FX We thank Beric Henderson, University of Sydney, Australia for providing
GFP-beta-catenin and Mark Frey of Children's Hospital Los Angeles for
pEGFP-N1 control vector. This work was supported by NIH grants AI40567
and NS73115 to N. V. P. and by the Intramural Program of the National
Institutes of Health to D. B. S.
NR 36
TC 21
Z9 21
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1462-5814
J9 CELL MICROBIOL
JI Cell Microbiol.
PD SEP
PY 2012
VL 14
IS 9
BP 1415
EP 1433
DI 10.1111/j.1462-5822.2012.01805.x
PG 19
WC Cell Biology; Microbiology
SC Cell Biology; Microbiology
GA 993GJ
UT WOS:000307844700009
PM 22519731
ER
PT J
AU Turan, TN
Lynn, MJ
Nizam, A
Lane, B
Egan, BM
Le, NA
Lopes-Virella, MF
Hermayer, KL
Benavente, O
White, CL
Brown, WV
Caskey, MF
Steiner, MR
Vilardo, N
Stufflebean, A
Derdeyn, CP
Fiorella, D
Janis, S
Chimowitz, MI
AF Turan, Tanya N.
Lynn, Michael J.
Nizam, Azhar
Lane, Bethany
Egan, Brent M.
Ngoc-Anh Le
Lopes-Virella, Maria F.
Hermayer, Kathie L.
Benavente, Oscar
White, Carole L.
Brown, W. Virgil
Caskey, Michelle F.
Steiner, Meghan R.
Vilardo, Nicole
Stufflebean, Andrew
Derdeyn, Colin P.
Fiorella, David
Janis, Scott
Chimowitz, Marc I.
CA SAMMPRIS Investigators
TI Rationale, Design, and Implementation of Aggressive Risk Factor
Management in the Stenting and Aggressive Medical Management for
Prevention of Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) Trial
SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES
LA English
DT Article
DE stroke; cerebrovascular circulation; risk factors; atherosclerosis;
lifestyle
ID TRANSIENT ISCHEMIC ATTACK; CORONARY-ARTERY-DISEASE; DENSITY-LIPOPROTEIN
CHOLESTEROL; HEALTH-CARE PROFESSIONALS; HIGH-DOSE ATORVASTATIN;
TREATMENT PANEL-III; CAROTID STENOSIS; DOUBLE-BLIND;
CARDIOVASCULAR-DISEASE; PHYSICAL-ACTIVITY
C1 [Turan, Tanya N.; Egan, Brent M.; Lopes-Virella, Maria F.; Hermayer, Kathie L.; Caskey, Michelle F.; Steiner, Meghan R.; Stufflebean, Andrew; Chimowitz, Marc I.] Med Univ S Carolina, Charleston, SC USA.
[Lynn, Michael J.; Nizam, Azhar; Lane, Bethany; Ngoc-Anh Le; Brown, W. Virgil] Emory Univ, Atlanta, GA 30322 USA.
[Ngoc-Anh Le; Brown, W. Virgil] Atlanta VAMC, Decatur, GA USA.
[Benavente, Oscar] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[White, Carole L.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Vilardo, Nicole] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA.
[Derdeyn, Colin P.] Washington Univ, St Louis, MI USA.
[Janis, Scott] NINDS, Bethesda, MD 20892 USA.
[Fiorella, David] SUNY Stony Brook, Stony Brook, NY 11794 USA.
RP Turan, TN (reprint author), MUSC Stroke Program 19 Hagood Ave,Suite 501,Harbo, Charleston, SC 29425 USA.
EM turan@musc.edu
OI Le, Ngoc-Anh/0000-0002-2634-4798; Turan, Tanya/0000-0001-5399-8845;
Derdeyn, Colin/0000-0002-5932-2683
FU United States Public Health Service National Institute of Neurological
Disorders and Stroke (NINDS) [U01 NS058728]; NIH-funded K23 grant award
[1 K23 NS069668-01A1]; Investigator-Sponsored Study Program of Astra
Zeneca; National Institute of Neurological Disorders and Stroke (NINDS)
[U01 NS058728]; NINDS K23 award [K23 NS069668]; NIH/NINDS [K23
NS069668]; National Eye Institute; Microvention Terumo; Medtronic;
Takeda; Novartis; NIH-funded study, BIOSIS: Biomarkers of Ischemic
Outcomes in Systemic Intracranial Stroke; American Diabetes Association
(ADA); Sanofi-Aventis; Eli Lilly; Novo Nordisk; NIH (DCCT/EDIC trial);
Astra Zeneca; NINDS [P50 55977, R01 NS051631, 1 R01 NS36643, 1 K24
NS050307, 1 R01 NS051688]; Codman/Johnson and Johnson; NFocus; W.L. Gore
and Associates; EV3/Covidien
FX The SAMMPRIS trial was funded by a research grant (U01 NS058728) from
the United States Public Health Service National Institute of
Neurological Disorders and Stroke (NINDS). In addition, Dr Tanya Turan's
NIH-funded K23 grant award (1 K23 NS069668-01A1), provided support for
her time and effort as the Director of Risk Factor Management. Corporate
Support: Stryker Neurovascular (formerly Boston Scientific
Neurovascular) provided study devices and supplemental funding for third
party device distribution, site monitoring and study auditing. This
research was also supported by the Investigator-Sponsored Study Program
of Astra Zeneca that donates rosuvastatin (Crestor) to study patients.;
Drs Turan, Derdeyn, Fiorella, Janis, and Chimowitz, and M.J.L. and B.L.
serve on the Executive Committee of the SAMMPRIS trial, which is funded
by the National Institute of Neurological Disorders and Stroke (NINDS)
(grant number: U01 NS058728). All except Dr Janis have received salary
support from the SAMMPRIS grant. Dr Turan is currently supported by a
NINDS K23 award (K23 NS069668). Dr Janis is the NINDS Program Officer
for the trial. Drs Egan, Le, Lopes-Virella, Hermayer, Benavente, White,
and Brown serve on the SAMMPRIS Risk Factor Committee and were
reimbursed from the SAMMPRIS grant for these efforts. A.N. serves at the
Statistical Coordinating Center and receives salary support from the
SAMMPRIS grant. M.C., M.S., N.V., and A.S. served in support roles for
the Risk Factor Committee and received salary support from the SAMMPRIS
grant for these efforts. None of the authors have any financial
relationship with the INTERxVENT Lifestyle Program. The following
investigators report additional support:; Dr Turan is the current
recipient of a K23 grant from NIH/NINDS (K23 NS069668) for research
related to intracranial stenosis. She currently serves on blinded
Neurological Events Adjudication Committees for an industry funded
diabetes mellitus drug trial (Boehringer Ingelheim), a NINDS-funded
observational study of vertebrobasilar stenosis (VERiTAS), and an
industry funded patent foramen ovale closure trial (W.L. Gore and
Associates) and is compensated for those activities. She has also served
as an expert witness in medical legal cases.; M.J.L. receives grant
support from the National Eye Institute. He is the principal
investigator of the Coordinating Center for Infant Aphakia Treatment
Study (EY013287) and a coinvestigator on the Core Grant for Vision
Research (EY006360).; B.F.L. has received consulting fees from
Microvention Terumo.; Dr Egan has received research support from
Medtronic, Takeda, and Novartis. He has been a consultant for Medtronic
and Blue Cross.; Dr Le has received research support for the NIH-funded
study, BIOSIS: Biomarkers of Ischemic Outcomes in Systemic Intracranial
Stroke.; Dr Hermayer has received research support from the American
Diabetes Association (ADA), Sanofi-Aventis, Eli Lilly, Novo Nordisk, and
the NIH (DCCT/EDIC trial). Dr Hermayer has received speakers' bureau
appointment payments from Sanofi-Aventis, Eli Lilly, Amylin, and
Boehringer Ingelheim.; Dr Brown has received research support from Astra
Zeneca, speakers' bureau appointment payments from Abbott, Merck,
Liposcience, and Kowa, and honoraria from Merck, Liposcience, and
Pfizer. Dr Brown has acted as a consultant to Amgen, Genzyme, Anthera,
Cerenis, Pfizer, and Bristol-Myers Squibb. He has also served as an
expert witness in a legal case involving Merck.; Dr Derdeyn receives
grant support from the NINDS (P50 55977; R01 NS051631). He is also on
the Scientific Advisory Board for W. L. Gore and Associates and is the
Chair of the Scientific Advisory Board for Pulse Therapeutics.; Dr
Fiorella has received institutional research support from Siemens
Medical Imaging and Microvention, consulting fees from Codman/Johnson
and Johnson, NFocus, W.L. Gore and Associates, and EV3/Covidien, and
royalties from Codman/Johnson and Johnson. He has received honoraria
from Scientia and has ownership interest in CVSL and Vascular
Simulations.; Dr Janis is a program director at the National Institute
of Neurological Disorders and Stroke.; Dr Chimowitz has received
research grants from NINDS to fund the WASID trial (1 R01 NS36643) and
to fund other research on intracranial stenosis (1 K24 NS050307 and 1
R01 NS051688). He currently serves on the stroke adjudication committee
of an industry funded osteoporosis drug trial (Merck and Co., Inc.) and
on the DSMB of another industry funded patent foramen ovale closure
trial (W.L. Gore and Associates) and is compensated for those
activities. He has also served as an expert witness in medical legal
cases.
NR 50
TC 21
Z9 21
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-7705
J9 CIRC-CARDIOVASC QUAL
JI Circ.-Cardiovasc. Qual. Outcomes
PD SEP
PY 2012
VL 5
IS 5
BP E51
EP E60
DI 10.1161/CIRCOUTCOMES.112.966911
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 010QK
UT WOS:000309109000003
PM 22991350
ER
PT J
AU Prasad, V
AF Prasad, Vinay
TI The conundrum of cost-effectiveness
SO CLEVELAND CLINIC JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID EFFICACY
C1 NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Prasad, V (reprint author), NCI, Med Oncol Branch, NIH, 10 Ctr Dr,10-12N226, Bethesda, MD 20892 USA.
EM vinayak.prasad@nih.gov
NR 6
TC 0
Z9 0
U1 0
U2 0
PU CLEVELAND CLINIC
PI CLEVELAND
PA 9500 EUCLID AVE, CLEVELAND, OH 44106 USA
SN 0891-1150
J9 CLEV CLIN J MED
JI Clevel. Clin. J. Med.
PD SEP
PY 2012
VL 79
IS 9
BP 610
EP 611
DI 10.3949/ccjm.79a.12129
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 004JP
UT WOS:000308678300004
PM 22949341
ER
PT J
AU Sacks, DB
AF Sacks, David B.
TI Measuring and reporting hemoglobin A1c
SO CLINICAL BIOCHEMISTRY
LA English
DT Editorial Material
ID DIABETES-MELLITUS; HUMAN BLOOD; STANDARDIZATION; SYSTEM
C1 [Sacks, David B.] NIH, Dept Lab Med, Bethesda, MD 20892 USA.
RP Sacks, DB (reprint author), Bldg 10,Rm 2C306,10 Ctr Dr, Bethesda, MD 20892 USA.
EM sacksdb@mail.nih.gov
OI Sacks, David/0000-0003-3100-0735
FU Intramural NIH HHS
NR 18
TC 1
Z9 1
U1 0
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0009-9120
J9 CLIN BIOCHEM
JI Clin. Biochem.
PD SEP
PY 2012
VL 45
IS 13-14
BP 1046
EP 1047
DI 10.1016/j.clinbiochem.2012.07.084
PG 2
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 007PA
UT WOS:000308899400009
PM 22842088
ER
PT J
AU Dominguez, D
Jawara, M
Martino, N
Sinaii, N
Grady, C
AF Dominguez, Dinora
Jawara, Mandy
Martino, Nicole
Sinaii, Ninet
Grady, Christine
TI Commonly performed procedures in clinical research: A benchmark for
payment
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Article
DE Paying research subjects; Remuneration; Compensating participants
ID PAYING RESEARCH PARTICIPANTS; RESEARCH SUBJECT; PRICE
AB Slow or insufficient enrollment in clinical research and a high demand for research participants raises questions about the need for and use of incentives to participate, including payment. Much of the available literature on payment to research participants focuses on ethical concerns, and rarely addresses guidelines, benchmarks, or formulas to assist investigators to assign or evaluate appropriate payment for individuals who take part in clinical research trials and procedures.
Using four years of data collected about the inconvenience units assigned by intramural investigators to selected clinical research procedures conducted at the National Institutes of Health (NIH) Clinical Center, this study provides payment benchmarks for commonly performed procedures.
Results were obtained from data collected on 36,273 incidents of payment made for procedures to research participants from August 2004 to August 2008. Analysis of the inconvenience units value assigned to specific procedures suggests that despite a wide distribution and frequent outliers, a convergence in practice around the center of distribution for most procedures does exist. As one of the first published studies reporting data reflecting payment amount for specific clinical research procedures, these data can guide investigators and institutional review boards as they establish and review an appropriate amount of payment to offer research participants. Our data may be useful in promoting payment standards for procedures, thereby complementing proposals or guidelines that advise payment calculations according to time and procedures. Published by Elsevier Inc.
C1 [Dominguez, Dinora; Jawara, Mandy; Martino, Nicole] NIH Clin Ctr, Off Commun Patient Recruitment & Publ Liaison, Bethesda, MD 20892 USA.
[Sinaii, Ninet] NIH Clin Ctr, Biostat & Clin Epidemiol Serv, Bethesda, MD 20892 USA.
[Grady, Christine] NIH Clin Ctr, Dept Bioeth, Bethesda, MD 20892 USA.
RP Martino, N (reprint author), NIH Clin Ctr, Off Commun Patient Recruitment & Publ Liaison, Bethesda, MD 20892 USA.
EM martinon@cc.nih.gov
FU Intramural Research Program of the NIH, Clinical Center
FX This research was supported in part by the Intramural Research Program
of the NIH, Clinical Center.
NR 20
TC 4
Z9 5
U1 2
U2 4
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 2012
VL 33
IS 5
BP 860
EP 868
DI 10.1016/j.cct.2012.05.001
PG 9
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 995XY
UT WOS:000308049800002
PM 22580210
ER
PT J
AU Enama, ME
Hu, ZH
Gordon, I
Costner, P
Ledgerwood, JE
Grady, C
AF Enama, Mary E.
Hu, Zonghui
Gordon, Ingelise
Costner, Pamela
Ledgerwood, Julie E.
Grady, Christine
CA VRC 306 307 Consent Study Teams
TI Randomization to standard and concise informed consent forms:
Development of evidence-based consent practices
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Article
DE Clinical trial; Informed consent; Institutional Review Board;
Comprehension; Research subject
ID CLINICAL-TRIALS; VACCINE; IMMUNOGENICITY
AB Background: Consent to participate in research is an important component of the conduct of ethical clinical trials. Current consent practices are largely policy-driven. This study was conducted to assess comprehension of study information and satisfaction with the consent form between subjects randomized to concise or to standard informed consent forms as one approach to developing evidence-based consent practices.
Methods: Participants (N = 111) who enrolled into two Phase I investigational influenza vaccine protocols (VRC 306 and VRC 307) at the NIH Clinical Center were randomized to one of two IRB-approved consents; either a standard or concise form. Concise consents had an average of 63% fewer words. All other aspects of the consent process were the same. Questionnaires about the study and the consent process were completed at enrollment and at the last visit in both studies.
Results: Subjects using concise consent forms scored as well as those using standard length consents in measures of comprehension (7 versus 7, p = 0.79 and 20 versus 21, p = 0.13), however, the trend was for the concise consent group to report feeling better informed. Both groups thought the length and detail of the consent form were appropriate.
Conclusions: Randomization of study subjects to different length IRB-approved consent forms as one method for developing evidence-based consent practices, resulted in no differences in study comprehension or satisfaction with the consent form. A concise consent form may be used ethically in the context of a consent process conducted by well-trained staff with opportunities for discussion and education throughout the study. Published by Elsevier Inc.
C1 [Enama, Mary E.; Gordon, Ingelise; Costner, Pamela; Ledgerwood, Julie E.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Hu, Zonghui] NIAID, Biostat Res Branch, Div Clin Res, NIH, Bethesda, MD 20892 USA.
[Grady, Christine] NIH Clin Ctr, Dept Bioeth, Bethesda, MD 20892 USA.
RP Enama, ME (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr,MSC 3017, Bethesda, MD 20892 USA.
EM Mary.Enama@nih.gov
FU National Institutes of Health (NIH) through the Vaccine Research Center
(VRC); National Institute of Allergy and Infectious Diseases (NIAID);
Department of Bioethics, NIH Clinical Center
FX National Institutes of Health (NIH) through the Vaccine Research Center
(VRC), National Institute of Allergy and Infectious Diseases (NIAID) and
the Department of Bioethics, NIH Clinical Center.
NR 15
TC 15
Z9 15
U1 0
U2 7
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 2012
VL 33
IS 5
BP 895
EP 902
DI 10.1016/j.cct.2012.04.005
PG 8
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 995XY
UT WOS:000308049800006
PM 22542645
ER
PT J
AU Ellis, SD
Carpenter, WR
Minasian, LM
Weiner, BJ
AF Ellis, Shellie D.
Carpenter, William R.
Minasian, Lori M.
Weiner, Bryan J.
TI Effect of state-mandated insurance coverage on accrual to community
cancer clinical trials
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Article
DE State policy; Clinical trial enrollment; Community Clinical Oncology
Program
ID ONCOLOGY PROGRAM; ASSURING ACCESS; POLICY CHANGE; CARE; ENROLLMENT;
PARTICIPATION; BARRIERS; COSTS; REIMBURSEMENT; LEGISLATION
AB Thirty-five U.S. states and territories have implemented policies requiring insurers to cover patient care costs in the context of cancer clinical trials: however, evidence of the effectiveness of these policies is limited. This study assesses the impact of state insurance mandates on clinical trial accrual among community-based practices participating in the NCI Community Clinical Oncology Program (CCOP), which enrolls approximately one-third of all NCI cancer trial participants. We analyzed CCOP clinical trial enrollment over 17 years in 37 states, 14 of which implemented coverage policies, using fixed effects least squares regression to estimate the effect of state policies on trial accrual among community providers, controlling for state and CCOP differences in capacity to recruit. Of 91 CCOPs active during this time, 28 were directly affected by coverage mandates. Average recruitment per CCOP between 1991 and 2007 was 95.1 participants per year (SD = 55.8). CCOPs in states with a mandate recruited similar numbers of participants compared to states without a mandate. In multivariable analysis, treatment trial accrual among CCOPs in states that had implemented a coverage mandate, was not statistically different than accrual among CCOPs in states that did not implement a coverage mandate ((beta = 2.95, p = 0.681). State mandates did not appear to confer a benefit in terms of CCOP clinical trial accrual. State policies vary in strength, which may have diluted their effect on accrual. Nonetheless, policy mandates alone may not have a meaningful impact on participation in clinical trials in these states. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Ellis, Shellie D.; Carpenter, William R.; Weiner, Bryan J.] Univ N Carolina, Dept Hlth Policy & Management, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA.
[Minasian, Lori M.] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
RP Ellis, SD (reprint author), Univ N Carolina, Dept Hlth Policy & Management, Gillings Sch Global Publ Hlth, 1101 McGavran Greenberg Hall,CB 7411, Chapel Hill, NC 27599 USA.
EM sdellis@email.unc.edu
RI Carpenter, William/E-5125-2013; Ellis, Shellie/I-4811-2015
OI Ellis, Shellie/0000-0002-3599-0804
FU National Cancer Institute at the National Institutes of Health
[R25CA116339, R01CA124402]
FX This work was supported by the National Cancer Institute at the National
Institutes of Health (R25CA116339 and R01CA124402). The sponsor had no
role in the design of the study, data collection or analysis, or
decision to submit the paper. As an expert in the Community Clinical
Oncology Program and clinical trial infrastructure, Dr Minasian
participated in the interpretation of results and writing of the
manuscript.
NR 39
TC 2
Z9 2
U1 0
U2 4
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 2012
VL 33
IS 5
BP 933
EP 941
DI 10.1016/j.cct.2012.06.001
PG 9
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 995XY
UT WOS:000308049800011
PM 22683991
ER
PT J
AU Mohebati, A
Knutson, A
Zhou, XK
Smith, JJ
Brown, PH
Dannenberg, AJ
Szabo, E
AF Mohebati, Arash
Knutson, Allison
Zhou, Xi Kathy
Smith, Judith J.
Brown, Powel H.
Dannenberg, Andrew J.
Szabo, Eva
TI A web-based screening and accrual strategy for a cancer prevention
clinical trial in healthy smokers
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Article
DE Clinical trial; Accrual; Recruitment; Advertising; Craigslist; Internet
ID RECRUITMENT EXPERIENCE; CHEMOPREVENTION
AB Screening and recruitment of qualified subjects for clinical trials is an essential component of translational research, and it can be quite challenging if the most efficient recruitment method is not utilized. In this report, we describe a successful web-based screening and accrual method used in a randomized prospective chemoprevention clinical trial with urinary biomarker endpoints. The targeted study population was a group of at-risk healthy current smokers with no evidence of lung disease. Craigslist was used as the sole recruitment modality for this study. All interested subjects were directed to a pre-screening website, in which subject questionnaire responses were linked to the study coordinator's secure e-mail account. Of the 429 initial inquiries, 189 individuals were initially eligible based on the questionnaire response. One hundred twenty-two people were telephone-screened, of whom 98 subjects were consented, 84 were randomized and 77 subjects completed the study successfully. Utilizing this single web-based advertising strategy, accrual for the trial was completed 7 months prior to the projected date. Craigslist is a cost effective and efficient web-based resource that can be utilized in accruing subjects to some chemoprevention trials. Published by Elsevier Inc.
C1 [Smith, Judith J.; Szabo, Eva] NCI, Lung & Upper Aerodigest Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Mohebati, Arash] Mem Sloan Kettering Canc Ctr, Dept Surg, Head & Neck Serv, New York, NY 10021 USA.
[Knutson, Allison; Dannenberg, Andrew J.] Cornell Univ, Dept Med, Weill Med Coll, New York, NY 10021 USA.
[Zhou, Xi Kathy] Cornell Univ, Dept Publ Hlth, Div Biostat & Epidemiol, Weill Med Coll, New York, NY 10021 USA.
[Brown, Powel H.] Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent, Div OVP Canc Prevent & Populat Sci, Houston, TX 77030 USA.
RP Szabo, E (reprint author), NCI, Lung & Upper Aerodigest Res Grp, Canc Prevent Div, NIH, 6130 Execut Blvd,Room 2132, Bethesda, MD 20892 USA.
EM szaboe@mail.nih.gov
FU NIH [T32 CA09685, N01-CN-35159]
FX This work was supported by NIH grant T32 CA09685 (AM) and by NIH
contract N01-CN-35159.
NR 17
TC 2
Z9 2
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1551-7144
J9 CONTEMP CLIN TRIALS
JI Contemp. Clin. Trials
PD SEP
PY 2012
VL 33
IS 5
BP 942
EP 948
DI 10.1016/j.cct.2012.07.004
PG 7
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 995XY
UT WOS:000308049800012
PM 22771576
ER
PT J
AU Winhusen, T
Brady, KT
Stitzer, M
Woody, G
Lindblad, R
Kropp, F
Brigham, G
Liu, D
Sparenborg, S
Sharma, G
VanVeldhuisen, P
Adinoff, B
Somoza, E
AF Winhusen, Theresa
Brady, Kathleen T.
Stitzer, Maxine
Woody, George
Lindblad, Robert
Kropp, Frankie
Brigham, Gregory
Liu, David
Sparenborg, Steven
Sharma, Gaurav
VanVeldhuisen, Paul
Adinoff, Bryon
Somoza, Eugene
TI Evaluation of buspirone for relapse-prevention in adults with cocaine
dependence: An efficacy trial conducted in the real world
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Article
DE Cocaine; Buspirone; Relapse-prevention; Contingency management
ID PLACEBO-CONTROLLED TRIAL; INCENTIVE-SENSITIZATION THEORY; ENHANCE
NALTREXONE TREATMENT; RANDOMIZED CLINICAL-TRIAL; CONTINGENCY MANAGEMENT;
SUBSTANCE USE; OPIOID DEPENDENCE; DEPRESSION SCALE; ATTENTIONAL BIAS;
HOSPITAL ANXIETY
AB Cocaine dependence is a significant public health problem for which there are currently no FDA-approved medications. Hence, identifying candidate compounds and employing an efficient evaluation process is crucial. This paper describes key design decisions made for a National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) study that uses a novel two-stage process to evaluate buspirone (60 mg/day) for cocaine-relapse prevention. The study includes pilot (N=60) and full-scale (estimated N=264) trials. Both trials will be randomized, double-blind, and placebo-controlled and both will enroll treatment-seeking cocaine-dependent participants engaged in inpatient/residential treatment and scheduled for outpatient treatment post-discharge. All participants will receive contingency management in which incentives are given for medication adherence as evaluated by the Medication Events Monitoring System (MEMS). The primary outcome measure is maximum days of continuous cocaine abstinence, as assessed by twice-weekly urine drug screens (UDS) and self-report, during the 15-week outpatient treatment phase. Drug-abuse outcomes include cocaine use as assessed by UDS and self-report of cocaine use, other substance use as assessed by LIDS and self-report of substance use (i.e., alcohol and/or illicit drugs), cocaine bingeing, HIV risk behavior, quality of life, functioning, and substance abuse treatment attendance. Unique aspects of the study include conducting an efficacy trial in community treatment programs, a two-stage process to efficiently evaluate buspirone, and an evaluation of mediators by which buspirone might exert a beneficial effect on relapse prevention. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Winhusen, Theresa; Kropp, Frankie; Brigham, Gregory; Somoza, Eugene] Univ Cincinnati, Dept Psychiat & Behav Neurosci, Coll Med, Cincinnati, OH 45220 USA.
[Brady, Kathleen T.] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA.
[Stitzer, Maxine] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Sch Med, Bayview Med Ctr, Baltimore, MD 21224 USA.
[Woody, George] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19106 USA.
[Lindblad, Robert; Sharma, Gaurav; VanVeldhuisen, Paul] EMMES Corp, Rockville, MD 20850 USA.
[Brigham, Gregory] Maryhaven, Columbus, OH 43207 USA.
[Liu, David; Sparenborg, Steven] NIDA, Ctr Clin Trials Network, Bethesda, MD 20892 USA.
[Adinoff, Bryon] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA.
[Adinoff, Bryon] VA N Texas Hlth Care Syst, Dallas, TX 75216 USA.
[Somoza, Eugene] Vet Affairs Med Ctr VISN 10, Cincinnati, OH 45220 USA.
RP Winhusen, T (reprint author), Univ Cincinnati, Dept Psychiat & Behav Neurosci, Coll Med, 3210 Jefferson Ave, Cincinnati, OH 45220 USA.
EM winhusen@carc.uc.edu
OI Winhusen, Theresa/0000-0002-3364-0739; Brigham,
Gregory/0000-0003-1150-4493
FU National Institute on Drug Abuse, National Drug Abuse Treatment Clinical
Trials Network, National Institutes of Health [U10-DA013732,
U10DA013727, U10 DA013034, U10DA013043, U10DA020024-07,
HHSN271200522081C, HHSN271200900034C]; National Institute on Drug Abuse;
National Institute on Alcohol Abuse and Alcoholism; Department of
Veterans Affairs
FX This work was supported by the National Institute on Drug Abuse,
National Drug Abuse Treatment Clinical Trials Network, National
Institutes of Health, by grants: U10-DA013732 to the University of
Cincinnati (Theresa Winhusen), U10DA013727 (Kathleen Brady and John
March), U10 DA013034 (Maxine L Stitzer and Robert P. Schwartz),
U10DA013043 (George Woody), U10DA020024-07 (Madhukar Trivedi) and
through contract nos. HHSN271200522081C and HHSN271200900034C.; Dr.
Adinoff has served as a consultant for Shook, Hardy & Bacon LLP (medical
malpractice consultant, tobacco companies) and Teva Pharmaceutical
Industries Ltd. and has received funding from the National Institute on
Drug Abuse, National Institute on Alcohol Abuse and Alcoholism, and the
Department of Veterans Affairs.
NR 69
TC 13
Z9 13
U1 4
U2 15
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 2012
VL 33
IS 5
BP 993
EP 1002
DI 10.1016/j.cct.2012.05.003
PG 10
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 995XY
UT WOS:000308049800018
PM 22613054
ER
PT J
AU Whang, W
Burg, MM
Carney, RM
Freedland, KE
Bigger, JT
Catellier, D
Czajkowski, S
Frasure-Smith, N
Haas, DC
Jaffe, AS
Lesperance, F
Medina, V
Duer-Hefele, J
Osorio, GA
Parsons, F
Shapiro, PA
Sheps, DS
Vaccarino, V
Davidson, KW
AF Whang, William
Burg, Matthew M.
Carney, Robert M.
Freedland, Kenneth E.
Bigger, J. Thomas
Catellier, Diane
Czajkowski, Susan
Frasure-Smith, Nancy
Haas, Donald C.
Jaffe, Allan S.
Lesperance, Francois
Medina, Vivian
Duer-Hefele, Joan
Osorio, Gabrielle A.
Parsons, Faith
Shapiro, Peter A.
Sheps, David S.
Vaccarino, Viola
Davidson, Karina W.
TI Design and baseline data from the vanguard of the Comparison of
Depression Interventions after Acute Coronary Syndrome (CODIACS)
randomized controlled trial
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Article
DE Clinical trial; Depression; Acute coronary syndrome
ID MYOCARDIAL-INFARCTION; HEART-DISEASE; CARE MANAGEMENT; METAANALYSIS;
ASSOCIATION; SYMPTOMS; EVENTS; ANTIDEPRESSANT; PSYCHOTHERAPY; PREVENTION
AB This paper describes the rationale and design of the vanguard for the Comparison of Depression Interventions after Acute Coronary Syndrome (CODIACS), a multicenter, randomized, controlled trial of a patient preference-based, stepped care protocol for persistent depressive symptoms after acute coronary syndrome (ACS). The overall aim of the vanguard phase was to determine whether the patient-preference, stepped care protocol, which is based on the intervention used in the recent Coronary Psychosocial Evaluation Studies (COPES) trial, was feasible in patients with recent ACS who were recruited from 5 geographically diverse sites. Innovative design features of this trial include randomization to either initial patient-preference of treatment or to a referred care arm in which the primary care provider decided upon care. Additionally, delivery of psychotherapy was accomplished by telephone, or webcam, depending upon patient preference. The vanguard phase provides estimates of eligibility and screening/enrollment ratios, patient acceptance of screening, and retention. In this report, we describe the innovative features and the baseline results of the vanguard phase of CODIACS. The data from this vanguard study will be used to finalize planning for a large, phase III clinical trial designed to evaluate the effect of treatment on depressive symptoms, coronary events, and death. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Whang, William; Burg, Matthew M.; Bigger, J. Thomas; Medina, Vivian; Duer-Hefele, Joan; Osorio, Gabrielle A.; Parsons, Faith; Shapiro, Peter A.; Davidson, Karina W.] Columbia Univ, Med Ctr, New York, NY USA.
[Carney, Robert M.; Freedland, Kenneth E.] Washington Univ, Sch Med, St Louis, MO USA.
[Catellier, Diane] Univ N Carolina, Chapel Hill, NC USA.
[Czajkowski, Susan] NHLBI, Washington, DC USA.
[Frasure-Smith, Nancy] McGill Univ, Montreal, PQ, Canada.
[Haas, Donald C.] Univ Penn, Philadelphia, PA 19104 USA.
[Jaffe, Allan S.] Mayo Clin, Rochester, MN USA.
[Frasure-Smith, Nancy; Lesperance, Francois] Univ Montreal, Montreal, PQ, Canada.
[Sheps, David S.; Vaccarino, Viola] Emory Univ, Sch Med, Atlanta, GA USA.
RP Davidson, KW (reprint author), PH9-314,622 W 168th St, New York, NY 10032 USA.
EM kd2124@mail.cumc.columbia.edu
RI Lesperance, Francois/C-4716-2015
OI Lesperance, Francois/0000-0003-4604-2823
FU NHLBI NIH HHS [R01 HL114924, K24 HL084034, P01 HL088117, RC2 HL101663]
NR 21
TC 5
Z9 5
U1 2
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1551-7144
J9 CONTEMP CLIN TRIALS
JI Contemp. Clin. Trials
PD SEP
PY 2012
VL 33
IS 5
BP 1003
EP 1010
DI 10.1016/j.cct.2012.05.005
PG 8
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 995XY
UT WOS:000308049800019
PM 22640924
ER
PT J
AU Fedorowski, A
Franceschini, N
Brody, J
Liu, CY
Verwoert, GC
Boerwinkle, E
Couper, D
Rice, KM
Rotter, JI
Mattace-Raso, F
Uitterlinden, A
Hofman, A
Almgren, P
Sjogren, M
Hedblad, B
Larson, MG
Newton-Cheh, C
Wang, TJ
Rose, KM
Psaty, BM
Levy, D
Witteman, J
Melander, O
AF Fedorowski, Artur
Franceschini, Nora
Brody, Jennifer
Liu, Chunyu
Verwoert, Germaine C.
Boerwinkle, Eric
Couper, David
Rice, Kenneth M.
Rotter, Jerome I.
Mattace-Raso, Francesco
Uitterlinden, Andre
Hofman, Albert
Almgren, Peter
Sjogren, Marketa
Hedblad, Bo
Larson, Martin G.
Newton-Cheh, Christopher
Wang, Thomas J.
Rose, Kathryn M.
Psaty, Bruce M.
Levy, Daniel
Witteman, Jacqueline
Melander, Olle
TI Orthostatic hypotension and novel blood pressure-associated gene
variants: Genetics of Postural Hemodynamics (GPH) Consortium
SO EUROPEAN HEART JOURNAL
LA English
DT Article
DE Orthostatic hypotension; Genetics; Single nucleotide polymorphism;
Steroid 17-alpha-hydroxylase; Natriuretic peptides; Adrenomedullin
ID GENOME-WIDE ASSOCIATION; PRIMARY SJOGRENS-SYNDROME; MALMO PREVENTIVE
PROJECT; ATHEROSCLEROSIS RISK; PREDICTS MORTALITY; HYPERTENSION;
COMMUNITIES; DIAGNOSIS; HEART; DISEASE
AB Orthostatic hypotension (OH), an independent predictor of mortality and cardiovascular events, strongly correlates with hypertension. Recent genome-wide studies have identified new loci influencing blood pressure (BP) in populations, but their impact on OH remains unknown.
A total of 38 970 men and women of European ancestry from five population-based cohorts were included, of whom 2656 (6.8) met the diagnostic criteria for OH (systolic/diastolic BP drop epsilon 20/10 mmHg within 3 min of standing). Thirty-one recently discovered BP-associated single nucleotide polymorphisms (SNPs) were examined using an additive genetic model and the major allele as referent. Relations between OH, orthostatic systolic BP response, and genetic variants were assessed by inverse variance-weighted meta-analysis. We found Bonferroni adjusted (P 0.0016) significant evidence for association between OH and the EBF1 locus (rs11953630, per-minor-allele odds ratio, 95 confidence interval: 0.90, 0.850.96; P 0.001), and nominal evidence (P 0.05) for CYP17A1 (rs11191548: 0.85, 0.750.95; P 0.005), and NPR3-C5orf23 (rs1173771: 0.92, 0.870.98; P 0.009) loci. Among subjects not taking BP-lowering drugs, three SNPs within the NPPA/NPPB locus were nominally associated with increased risk of OH (rs17367504: 1.13, 1.021.24; P 0.02, rs198358: 1.10, 1.011.20; P 0.04, and rs5068: 1.22, 1.041.43; P 0.01). Moreover, an ADM variant was nominally associated with continuous orthostatic systolic BP response in the adjusted model (P 0.04).
The overall association between common gene variants in BP loci and OH was generally weak and the direction of effect inconsistent with resting BP findings. These results suggest that OH and resting BP share few genetic components.
C1 [Fedorowski, Artur; Melander, Olle] Skane Univ Hosp, Ctr Emergency Med, S-20502 Malmo, Sweden.
[Fedorowski, Artur; Almgren, Peter; Sjogren, Marketa; Hedblad, Bo; Melander, Olle] Lund Univ, Clin Res Ctr, Dept Clin Sci, Malmo, Sweden.
[Franceschini, Nora; Rose, Kathryn M.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Brody, Jennifer; Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Brody, Jennifer; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Brody, Jennifer; Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Liu, Chunyu; Larson, Martin G.; Wang, Thomas J.; Levy, Daniel] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Liu, Chunyu; Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
[Verwoert, Germaine C.; Mattace-Raso, Francesco; Uitterlinden, Andre; Hofman, Albert; Witteman, Jacqueline] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Verwoert, Germaine C.; Mattace-Raso, Francesco; Uitterlinden, Andre] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Verwoert, Germaine C.; Uitterlinden, Andre; Witteman, Jacqueline] Netherlands Genome Initiat NGI, Netherlands Consortium Healthy Aging NCHA, The Hague, Netherlands.
[Boerwinkle, Eric] Univ Texas Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX USA.
[Couper, David] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA.
[Rice, Kenneth M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Larson, Martin G.] Boston Univ, Dept Math, Boston, MA 02215 USA.
[Newton-Cheh, Christopher; Wang, Thomas J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
[Newton-Cheh, Christopher; Wang, Thomas J.] Harvard Univ, Sch Med, Boston, MA USA.
[Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Newton-Cheh, Christopher] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
RP Fedorowski, A (reprint author), Skane Univ Hosp, Ctr Emergency Med, Entrance 35,Floor 2, S-20502 Malmo, Sweden.
EM artur.fedorowski@med.lu.se
RI Rice, Kenneth/A-4150-2013; Mattace- Raso, Francesco/L-2541-2015;
OI Rice, Kenneth/0000-0001-5779-4495; Larson, Martin/0000-0002-9631-1254
FU Lund University; Zoll
FX Detailed information on the sources of funding can be found in the
Supplementary material online (Funding and Acknowledgements Section).
Funding to pay the Open Access publication charges for this article was
provided by Lund University.; B.M.P. serves on a DSMB for a clinical
trial of a device funded by the manufacturer (Zoll).
NR 40
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U2 5
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 2012
VL 33
IS 18
BP 2331
EP 2341
DI 10.1093/eurheartj/ehs058
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 007KF
UT WOS:000308886500014
PM 22504314
ER
PT J
AU Gallo, E
Katzman, S
Villarino, AV
AF Gallo, Eugenio
Katzman, Shoshana
Villarino, Alejandro V.
TI IL-13-producing Th1 and Th17 cells characterize adaptive responses to
both self and foreign antigens
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
DE Adaptative response; IL-13; Th1; Th2; Th17
ID CD4(+) T-CELLS; UNIQUE FUNCTIONS; IL-4; PLASTICITY; MECHANISMS;
EXPRESSION; CYTOKINE; PRODUCE; SUBSET
AB In helper T cells, IL-13 is traditionally considered a Th2-type cytokine that is coexpressed with IL-4. Using mouse models of immunization and autoimmunity, we demonstrate that IL-13 is frequently uncoupled from IL-4, and that it can be produced by both IFN-gamma(+) Th1 cells and IL-17(+) Th17 cells. We report that these IL-13-producing Th1 and Th17 cells are distinct from classical IL-4(+) Th2 cells and that they are relatively common, appearing in the context of both protective and pathogenic T-cell responses. We also demonstrate that IL-13 and Th2-type cytokines can have important consequences in Th1- and Th17-dominated settings, such as lymphopenia-induced autoimmune disease, where they can be either pro- or anti-inflammatory, depending on whether they act on innate or adaptive immune cells. Taken together, our studies indicate that IL-13 production is more widespread than previously appreciated and that blocking this cytokine may have therapeutic benefits even in settings where traditional IL-4-driven Th2-type responses are not evident.
C1 [Gallo, Eugenio; Katzman, Shoshana; Villarino, Alejandro V.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA.
RP Villarino, AV (reprint author), NIAMSD, NIH, 9000 Rockville Pike,10 Ctr Dr,Bldg 10,Room 13C120, Bethesda, MD 20892 USA.
EM Alejandro.Villarino@nih.gov
OI Villarino, Alejandro/0000-0001-8068-2176
FU NIH [RO1AI64677, PA-05-015]
FX The authors thank Dr. Abul Abbas (UCSF) for mice, reagents, and advice.
We also thank Dr. J. O'Shea (NIH) and members of the O'Shea laboratory
for discussions. Research supported by NIH grant RO1AI64677 and a
minority supplement to A. V. V. (PA-05-015).
NR 17
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U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-2980
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD SEP
PY 2012
VL 42
IS 9
BP 2322
EP 2328
DI 10.1002/eji.201142227
PG 7
WC Immunology
SC Immunology
GA 000RH
UT WOS:000308404800015
PM 22684943
ER
PT J
AU Brown, PL
Shepard, PD
Elmer, GI
Stockman, S
McFarland, R
Mayo, CL
Cadet, JL
Krasnova, IN
Greenwald, M
Schoonover, C
Vogel, MW
AF Brown, P. Leon
Shepard, Paul D.
Elmer, Greg I.
Stockman, Sara
McFarland, Rebecca
Mayo, Cheryl L.
Cadet, Jean Lud
Krasnova, Irina N.
Greenwald, Martin
Schoonover, Carrie
Vogel, Michael W.
TI Altered spatial learning, cortical plasticity and hippocampal anatomy in
a neurodevelopmental model of schizophrenia-related endophenotypes
SO EUROPEAN JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE animal model; cytosine arabinoside; long-term potentiation;
methylazoxymethanol; rat; spatial learning
ID LONG-TERM POTENTIATION; PREFRONTAL CORTEX PATHWAY; METHYLAZOXYMETHANOL
ACETATE; ANIMAL-MODEL; CELL DISARRAY; NEURON SIZE; ARA-C; RAT;
IMPAIRMENT; DOPAMINE
AB Adult rats exposed to the DNA-methylating agent methylazoxymethanol on embryonic day 17 show a pattern of neurobiological deficits that model some of the neuropathological and behavioral changes observed in schizophrenia. Although it is generally assumed that these changes reflect targeted disruption of embryonic neurogenesis, it is unknown whether these effects generalise to other antimitotic agents administered at different stages of development. In the present study, neurochemical, behavioral and electrophysiological techniques were used to determine whether exposure to the antimitotic agent Ara-C later in development recapitulates some of the changes observed in methylazoxymethanol (MAM)-treated animals and in patients with schizophrenia. Male rats exposed to Ara-C (30 mg/kg/day) at embryonic days 19.5 and 20.5 show reduced cell numbers and heterotopias in hippocampal CA1 and CA2/3 regions, respectively, as well as cell loss in the superficial layers of the pre- and infralimbic cortex. Birth date labeling with bromodeoxyuridine reveals that the cytoarchitectural changes in CA2/3 are a consequence rather that a direct result of disrupted cortical neurogenesis. Ara-C-treated rats possess elevated levels of cortical dopamine and DOPAC (3,4-didyhydroxypheylacetic acid) but no change in norepinephrine or serotonin. Ara-C-treated rats are impaired in their ability to learn the Morris water maze task and showed diminished synaptic plasticity in the hippocampocortical pathway. These data indicate that disruption of neurogenesis at embryonic days 19.5 and 20.5 constitutes a useful model for the comparative study of deficits observed in other gestational models and their relationship to cognitive changes observed in schizophrenia.
C1 [Brown, P. Leon; Shepard, Paul D.; Elmer, Greg I.; Stockman, Sara; McFarland, Rebecca; Mayo, Cheryl L.; Greenwald, Martin; Schoonover, Carrie; Vogel, Michael W.] Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA.
[Brown, P. Leon; Shepard, Paul D.; Elmer, Greg I.] Univ Maryland, Sch Med, Program Neurosci, Baltimore, MD 21201 USA.
[Cadet, Jean Lud; Krasnova, Irina N.] NIDA, Mol Neuropsychiat Res Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD USA.
RP Vogel, MW (reprint author), NIMH, Off Res Training & Career Dev, Div Neurosci & Basic Behav Sci, 6001 Execut Blvd, Bethesda, MD 20892 USA.
EM vogel.michael1066@gmail.com
OI Vogel, Michael/0000-0002-8402-1495; McFarland,
Rebecca/0000-0003-0081-2677
FU PHS [MH-076854]
FX We gratefully acknowledge the assistance of Dr Adam C. Puche with
photomicroscopy. This study was supported by PHS grant MH-076854
(M.W.V.). This article was prepared while M.W.V. was employed at the
University of Maryland School of Medicine. The opinions expressed in
this article are the authors' own and do not reflect the view of the
National Institutes of Health, the Department of Health and Human
Services, or the United States government.
NR 62
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U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0953-816X
J9 EUR J NEUROSCI
JI Eur. J. Neurosci.
PD SEP
PY 2012
VL 36
IS 6
BP 2773
EP 2781
DI 10.1111/j.1460-9568.2012.08204.x
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 008EU
UT WOS:000308941000006
PM 22762562
ER
PT J
AU Mesen, TB
Segars, JH
AF Mesen, Tolga B.
Segars, James H.
TI The genuine empty follicle syndrome: is the king naked? REPLY
SO FERTILITY AND STERILITY
LA English
DT Letter
C1 [Mesen, Tolga B.; Segars, James H.] NICHHD, Program Reprod & Adult Endocrinol, Bethesda, MD 20892 USA.
[Mesen, Tolga B.] Carolinas Med Ctr, Dept Obstet & Gynecol, Charlotte, NC 28203 USA.
RP Mesen, TB (reprint author), NICHHD, Program Reprod & Adult Endocrinol, Bethesda, MD 20892 USA.
NR 6
TC 0
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U1 2
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2012
VL 98
IS 3
BP E22
EP E22
DI 10.1016/j.fertnstert.2012.07.1099
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 000QO
UT WOS:000308402400005
ER
PT J
AU Gao, B
Waisman, A
AF Gao, Bin
Waisman, Ari
TI Th17 Cells Regulate Liver Fibrosis by Targeting Multiple Cell Types:
Many Birds With One Stone
SO GASTROENTEROLOGY
LA English
DT Editorial Material
ID HEPATITIS; DISEASE; IL-17; INTERLEUKIN-22; INFLAMMATION; HEPATOCYTES;
MACROPHAGES; CYTOKINES; IL-22
C1 [Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA.
[Waisman, Ari] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Mol Med, Mainz, Germany.
RP Gao, B (reprint author), NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA.
EM bgao@mail.nih.gov; waisman@uni-mainz.de
RI Waisman, Ari/C-7383-2015
OI Waisman, Ari/0000-0003-4304-8234
NR 20
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U1 1
U2 4
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD SEP
PY 2012
VL 143
IS 3
BP 536
EP 539
DI 10.1053/j.gastro.2012.07.031
PG 4
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 000PO
UT WOS:000308399300032
PM 22842060
ER
PT J
AU Reidy, M
Miot, M
Masison, DC
AF Reidy, Michael
Miot, Marika
Masison, Daniel C.
TI Prokaryotic Chaperones Support Yeast Prions and Thermotolerance and
Define Disaggregation Machinery Interactions
SO GENETICS
LA English
DT Article
ID SHOCK PROTEIN COMPLEMENTS; SACCHAROMYCES-CEREVISIAE; PSI+ PRION; HSP104
CHAPERONE; MOLECULAR CHAPERONE; AGGREGATED PROTEINS; COMMON MECHANISM;
CENTRAL PORE; CELL-GROWTH; PROPAGATION
AB Saccharomyces cerevisiae Hsp104 and Escherichia coli ClpB are Hsp100 family AAA+ chaperones that provide stress tolerance by cooperating with Hsp70 and Hsp40 to solubilize aggregated protein. Hsp104 also remodels amyloid in vitro and promotes propagation of amyloid prions in yeast, but ClpB does neither, leading to a view that Hsp104 evolved these activities. Although biochemical analyses identified disaggregation machinery components required for resolubilizing proteins, interactions among these components required for in vivo functions are not clearly defined. We express prokaryotic chaperones in yeast to address these issues and find ClpB supports both prion propagation and thermotolerance in yeast if it is modified to interact with yeast Hsp70 or if E. coli Hsp70 and its cognate nucleotide exchange factor (NEF) are present. Our findings show prion propagation and thermotolerance in yeast minimally require cooperation of species-specific Hsp100, Hsp70, and NEF with yeast Hsp40. The functions of this machinery in prion propagation were directed primarily by Hsp40 Sis1p, while thermotolerance relied mainly on Hsp40 Ydj1p. Our results define cooperative interactions among these components that are specific or interchangeable across life kingdoms and imply Hsp100 family disaggregases possess intrinsic amyloid remodeling activity.
C1 [Reidy, Michael; Masison, Daniel C.] NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
[Miot, Marika] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Masison, DC (reprint author), NIDDKD, Lab Biochem & Genet, NIH, Bldg 8,Room 225,8 Ctr Dr, Bethesda, MD 20892 USA.
EM masisond@helix.nih.gov
OI miot, marie-caroline/0000-0002-3697-6510; Reidy,
Michael/0000-0002-9290-7595
FU NIH, National Institute of Diabetes and Digestive and Kidney Diseases;
National Cancer Institute, Center for Cancer Research
FX We thank Sue Wickner [National Institutes of Health (NIH), Bethesda, MD]
and John Glover (University of Toronto) for antibodies, and NIH
colleagues for insightful discussion and critical reading of the
manuscript. This work was supported by the Intramural Research Program
of the NIH, National Institute of Diabetes and Digestive and Kidney
Diseases, and National Cancer Institute, Center for Cancer Research.
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PU GENETICS SOC AM
PI BETHESDA
PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
SN 0016-6731
J9 GENETICS
JI Genetics
PD SEP
PY 2012
VL 192
IS 1
BP 185
EP U389
DI 10.1534/genetics.112.142307
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA 009BZ
UT WOS:000309001800014
PM 22732191
ER
PT J
AU Chiang, CWK
Liu, CT
Lettre, G
Lange, LA
Jorgensen, NW
Keating, BJ
Vedantam, S
Nock, NL
Franceschini, N
Reiner, AP
Demerath, EW
Boerwinkle, E
Rotter, JI
Wilson, JG
North, KE
Papanicolaou, GJ
Cupples, LA
Murabito, JM
Hirschhorn, JN
AF Chiang, Charleston W. K.
Liu, Ching-Ti
Lettre, Guillaume
Lange, Leslie A.
Jorgensen, Neal W.
Keating, Brendan J.
Vedantam, Sailaja
Nock, Nora L.
Franceschini, Nora
Reiner, Alex P.
Demerath, Ellen W.
Boerwinkle, Eric
Rotter, Jerome I.
Wilson, James G.
North, Kari E.
Papanicolaou, George J.
Cupples, L. Adrienne
Murabito, Joanne M.
Hirschhorn, Joel N.
CA Genetic Invest ANthropometric Trai
TI Ultraconserved Elements in the Human Genome: Association and
Transmission Analyses of Highly Constrained Single-Nucleotide
Polymorphisms
SO GENETICS
LA English
DT Article
ID CONSERVED NONCODING SEQUENCES; WIDE ASSOCIATION; GENOTYPING ERRORS;
HUMAN HEIGHT; TRANSMISSION/DISEQUILIBRIUM TEST; REPRODUCTIVE FITNESS;
COMPLEX TRAITS; FAMILY DATA; VARIANTS; LOCI
AB Ultraconserved elements in the human genome likely harbor important biological functions as they are dosage sensitive and are able to direct tissue-specific expression. Because they are under purifying selection, variants in these elements may have a lower frequency in the population but a higher likelihood of association with complex traits. We tested a set of highly constrained SNPs (hcSNPs) distributed genome-wide among ultraconserved and nearly ultraconserved elements for association with seven traits related to reproductive (age at natural menopause, number of children, age at first child, and age at last child) and overall [longevity, body mass index (BMI), and height] fitness. Using up to 24,047 European-American samples from the National Heart, Lung, and Blood Institute Candidate Gene Association Resource (CARe), we observed an excess of associations with BMI and height. In an independent replication panel the most strongly associated SNPs showed an 8.4-fold enrichment of associations at the nominal level, including three variants in previously identified loci and one in a locus (DENND1A) previously shown to be associated with polycystic ovary syndrome. Finally, using 1430 family trios, we showed that the transmissions from heterozygous parents to offspring of the derived alleles of rare (frequency <= 0.5%) hcSNPs are not biased, particularly after adjusting for the rates of genotype missingness and error in the data. The lack of transmission bias ruled out an immediately and strongly deleterious effect due to the rare derived alleles, consistent with the observation that mice homozygous for the deletion of ultraconserved elements showed no overt phenotype. Our study also illustrated the importance of carefully modeling potential technical confounders when analyzing genotype data of rare variants.
C1 [Chiang, Charleston W. K.; Vedantam, Sailaja; Hirschhorn, Joel N.] Childrens Hosp, Genet Program, Boston, MA 02115 USA.
[Chiang, Charleston W. K.; Vedantam, Sailaja; Hirschhorn, Joel N.] Childrens Hosp, Div Genet, Boston, MA 02115 USA.
[Chiang, Charleston W. K.; Vedantam, Sailaja; Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Chiang, Charleston W. K.; Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Chiang, Charleston W. K.; Vedantam, Sailaja; Hirschhorn, Joel N.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
[Liu, Ching-Ti; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Lettre, Guillaume] Univ Montreal, Fac Med, Montreal, PQ H3C 3J7, Canada.
[Lettre, Guillaume] Inst Cardiol Montreal, Montreal, PQ H1T 1C8, Canada.
[Lange, Leslie A.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Jorgensen, Neal W.] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA.
[Keating, Brendan J.] Univ Penn, Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Keating, Brendan J.] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA.
[Nock, Nora L.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
[Franceschini, Nora; North, Kari E.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Reiner, Alex P.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Demerath, Ellen W.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA.
[Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
[Papanicolaou, George J.; Cupples, L. Adrienne] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Murabito, Joanne M.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02215 USA.
RP Hirschhorn, JN (reprint author), Childrens Hosp, Genet Program, CLS 16065,300 Longwood Ave, Boston, MA 02115 USA.
EM joelh@broadinstitute.org
OI Nock, Nora L./0000-0002-6476-6692; Chiang,
Charleston/0000-0002-0668-7865
FU National Science Foundation; National Heart, Lung, and Blood Institute
(NHLBI) [HHSN268200960009C, HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268 201100009C,
HHSN268201100010C, HHSN268201100011C, HHSN268201100012C]
FX The authors thank J. Aylor, N. Dermond, R. Goodloe, C. Johnson,, E.
Larkin, A. Newman, W. Post, S. Redline, P. Schreiner, N. Zakai, and X.
Zhu for assistance with phenotype definition within different CARe
cohorts; members of the Candidate Gene Association Resource (CARe)
Anthropometric and Aging working groups, past and present members of the
Hirschhorn laboratory, and C.-t. Wu for ideas and comments; Vivian U.
for assistance in the graphical representation in Figure 3; and D.
Farlow, Y. Meng, C. D. Palmer, and T. Young for assistance with analysis
within the CARe framework. The authors thank the staff and participants
of the Atherosclerosis Risk in Communities (ARIC) study for their
important contributions. This work was supported by a graduate research
fellowship from the National Science Foundation (to C. W. K. C.). The
CARe acknowledges the support of the National Heart, Lung, and Blood
Institute (NHLBI) and the contributions of the research institutions,
study investigators, field staff, and study participants in creating
this resource for biomedical research (NHLBI contract no.
HHSN268200960009C). The following eight parent studies have contributed
parent study data, ancillary study data, and DNA samples through the
Broad Institute (N01-HC-65226) to create this genotype/phenotype
database for wide dissemination to the biomedical research community:
the ARIC study, the Cardiovascular Health Study (CHS), the Cleveland
Family Study (CFS), the Coronary Artery Risk Development in Young Adults
(CARDIA) study, the Framingham Heart Study (FHS), the Jackson Heart
Study (JHS), the Multi-Ethnic Study of Atherosclerosis (MESA), and the
Sleep Heart Health Study (SHHS). Individual study funding attributions
can be obtained at
http://public.nhlbi.nih.gov/GeneticsGenomics/home/care.aspx. The
Atherosclerosis Risk in Communities Study is carried out as a
collaborative study supported by NHLBI contracts HHSN268201100005C,
HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268
201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C.
NR 49
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U1 0
U2 13
PU GENETICS SOC AM
PI BETHESDA
PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
SN 0016-6731
J9 GENETICS
JI Genetics
PD SEP
PY 2012
VL 192
IS 1
BP 253
EP U515
DI 10.1534/genetics.112.141945
PG 28
WC Genetics & Heredity
SC Genetics & Heredity
GA 009BZ
UT WOS:000309001800019
PM 22714408
ER
PT J
AU Clatworthy, MR
Petrie-Aronin, C
Mathews, R
Smith, KGC
Germain, RN
AF Clatworthy, M. R.
Petrie-Aronin, C.
Mathews, R.
Smith, K. G. C.
Germain, R. N.
TI Immune complexes enhance dendritic cell migration to lymph nodes
SO IMMUNOLOGY
LA English
DT Meeting Abstract
CT European Congress of Immunology
CY SEP 05-08, 2012
CL Glasgow, SCOTLAND
C1 [Clatworthy, M. R.; Mathews, R.; Smith, K. G. C.] Univ Cambridge, Cambridge Inst Med Res, Cambridge, England.
[Petrie-Aronin, C.; Germain, R. N.] LSB NIAID, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0019-2805
J9 IMMUNOLOGY
JI Immunology
PD SEP
PY 2012
VL 137
SU 1
SI SI
BP 68
EP 68
PG 1
WC Immunology
SC Immunology
GA 011TW
UT WOS:000309189100158
ER
PT J
AU Zhou, Q
Haupt, S
Prots, I
Thuemmler, K
Kremmer, E
Lipsky, P
Schulze-Koops, H
Skapenko, A
AF Zhou, Q.
Haupt, S.
Prots, I.
Thuemmler, K.
Kremmer, E.
Lipsky, P.
Schulze-Koops, H.
Skapenko, A.
TI miRNA regulation of cell proliferation by targeting the expression of
GARP
SO IMMUNOLOGY
LA English
DT Meeting Abstract
CT European Congress of Immunology
CY SEP 05-08, 2012
CL Glasgow, SCOTLAND
C1 [Zhou, Q.; Haupt, S.; Prots, I.; Thuemmler, K.; Schulze-Koops, H.; Skapenko, A.] Univ Munich, Med Klin & Poliklin 4, Div Rheumatol & Clin Immunol, Munich, Germany.
[Kremmer, E.] Helmholz Ctr Munich Deutsch Forschungszentrum Ges, Inst Mol Immunol, Munich, Germany.
[Lipsky, P.] NIAMSD, Autoimunigy Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0019-2805
J9 IMMUNOLOGY
JI Immunology
PD SEP
PY 2012
VL 137
SU 1
SI SI
BP 74
EP 74
PG 1
WC Immunology
SC Immunology
GA 011TW
UT WOS:000309189100174
ER
PT J
AU Turner, JE
Wilhelm, C
Helmby, H
Stockinger, B
AF Turner, J. E.
Wilhelm, C.
Helmby, H.
Stockinger, B.
TI IL-9 enhances accumulation of pulmonary IL-13(+)IL-5(+) innate lymphoid
cells and promotes lung damage repair after N. brasiliensis infection
SO IMMUNOLOGY
LA English
DT Meeting Abstract
CT European Congress of Immunology
CY SEP 05-08, 2012
CL Glasgow, SCOTLAND
C1 [Turner, J. E.; Stockinger, B.] MRC Natl Inst Med Res, London, England.
[Wilhelm, C.] NIH, Mucosal Immun Sect, Bethesda, MD 20892 USA.
[Helmby, H.] London Sch Hygene & Trop Med, London, England.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0019-2805
J9 IMMUNOLOGY
JI Immunology
PD SEP
PY 2012
VL 137
SU 1
SI SI
BP 99
EP 99
PG 1
WC Immunology
SC Immunology
GA 011TW
UT WOS:000309189100231
ER
PT J
AU Jakobsen, M
Anderse, A
Berg, R
Bak, R
Hansen, K
Jin, T
Jensen, S
Ostergaard, L
Fitzgerald, K
Towers, G
Xiao, T
Mogensen, T
Mikkelsen, J
Paludan, S
AF Jakobsen, M.
Anderse, A.
Berg, R.
Bak, R.
Hansen, K.
Jin, T.
Jensen, S.
Ostergaard, L.
Fitzgerald, K.
Towers, G.
Xiao, T.
Mogensen, T.
Mikkelsen, J.
Paludan, S.
TI IFI16 senses stem-rich single-stranded DNA and induces innate immune
responses to control HIV replication
SO IMMUNOLOGY
LA English
DT Meeting Abstract
CT European Congress of Immunology
CY SEP 05-08, 2012
CL Glasgow, SCOTLAND
C1 [Jakobsen, M.; Anderse, A.; Bak, R.; Hansen, K.; Jensen, S.; Mikkelsen, J.; Paludan, S.] Aarhus Univ, Inst Biomed, Aarhus C, Denmark.
[Berg, R.; Ostergaard, L.; Mogensen, T.] Aarhus Univ Hosp, Dept Infect Dis, DK-8000 Aarhus C, Denmark.
[Jin, T.; Xiao, T.] NIAID, Immunol Lab, Bethasda, MD USA.
[Fitzgerald, K.] Univ Massachusetts, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA.
[Towers, G.] UCL, MRC Ctr Med Mol Virol, London, England.
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 0019-2805
J9 IMMUNOLOGY
JI Immunology
PD SEP
PY 2012
VL 137
SU 1
SI SI
BP 154
EP 154
PG 1
WC Immunology
SC Immunology
GA 011TW
UT WOS:000309189101092
ER
PT J
AU Roulland, S
Sungalee, S
Mamessier, E
Morgado, E
Gregoire, E
Monvoisin, C
Menard, C
Navarro, JM
Eberle, FC
Chasson, L
Mancini, S
Tellier, J
Piquenot, JM
Ruminy, P
Chetaille, B
Jaffe, ES
Schiff, C
Hardwigsen, J
Tarte, K
Nadel, B
AF Roulland, S.
Sungalee, S.
Mamessier, E.
Morgado, E.
Gregoire, E.
Monvoisin, C.
Menard, C.
Navarro, J. M.
Eberle, F. C.
Chasson, L.
Mancini, S.
Tellier, J.
Piquenot, J. M.
Ruminy, P.
Chetaille, B.
Jaffe, E. S.
Schiff, C.
Hardwigsen, J.
Tarte, K.
Nadel, B.
TI Iterative germinal center re-entries of memory B-cells with t(14;18)
translocation and early steps of follicular lymphoma progression
SO IMMUNOLOGY
LA English
DT Meeting Abstract
CT European Congress of Immunology
CY SEP 05-08, 2012
CL Glasgow, SCOTLAND
C1 [Roulland, S.; Sungalee, S.; Mamessier, E.; Morgado, E.; Navarro, J. M.; Chasson, L.; Mancini, S.; Tellier, J.; Schiff, C.; Nadel, B.] INSERM, U1104, Ctr Immunol Marseille Luminy, F-13258 Marseille, France.
[Gregoire, E.; Hardwigsen, J.] Hop Conception, Dept Surg & Liver Transplantat, Marseille, France.
[Monvoisin, C.; Menard, C.; Tarte, K.] INSERM, U917, EFS Bretagne, Rennes, France.
[Eberle, F. C.; Jaffe, E. S.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Piquenot, J. M.; Ruminy, P.] INSERM, Ctr Henri Becquerel, U918, Rouen, France.
[Chetaille, B.] Inst J Paoli I Calmettes, Dept Pathol, F-13009 Marseille, France.
RI Nadel, Bertrand/J-2197-2014
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 0019-2805
J9 IMMUNOLOGY
JI Immunology
PD SEP
PY 2012
VL 137
SU 1
SI SI
BP 163
EP 163
PG 1
WC Immunology
SC Immunology
GA 011TW
UT WOS:000309189101116
ER
PT J
AU Mamessier, E
Song, JY
Eberle, FE
Chetaille, B
Birnbaum, D
Pittaluga, S
Roulland, S
Jaffe, ES
Nadel, B
AF Mamessier, E.
Song, J. Y.
Eberle, F. E.
Chetaille, B.
Birnbaum, D.
Pittaluga, S.
Roulland, S.
Jaffe, E. S.
Nadel, B.
TI Early oncogenic hits in follicular lymphoma precursors
SO IMMUNOLOGY
LA English
DT Meeting Abstract
CT European Congress of Immunology
CY SEP 05-08, 2012
CL Glasgow, SCOTLAND
C1 [Mamessier, E.; Roulland, S.; Nadel, B.] CIML, Marseille, France.
[Song, J. Y.; Eberle, F. E.; Pittaluga, S.; Jaffe, E. S.] NIH, Pathol Lab, Bethesda, MD 20892 USA.
[Chetaille, B.] IPC, Pathol Lab, Marseille, France.
[Birnbaum, D.] CRCM, Marseille, France.
RI Nadel, Bertrand/J-2197-2014
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 0019-2805
J9 IMMUNOLOGY
JI Immunology
PD SEP
PY 2012
VL 137
SU 1
SI SI
BP 164
EP 164
PG 1
WC Immunology
SC Immunology
GA 011TW
UT WOS:000309189101119
ER
PT J
AU Kole, A
He, J
Rivollier, A
Kitamura, K
Maloy, K
Kelsall, B
AF Kole, A.
He, J.
Rivollier, A.
Kitamura, K.
Maloy, K.
Kelsall, B.
TI Essential role for type I interferons in the regulation of T cell
mediated colitis
SO IMMUNOLOGY
LA English
DT Meeting Abstract
CT European Congress of Immunology
CY SEP 05-08, 2012
CL Glasgow, SCOTLAND
C1 [Kole, A.; Maloy, K.] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England.
[He, J.; Rivollier, A.; Kitamura, K.; Kelsall, B.] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0019-2805
J9 IMMUNOLOGY
JI Immunology
PD SEP
PY 2012
VL 137
SU 1
SI SI
BP 213
EP 213
PG 1
WC Immunology
SC Immunology
GA 011TW
UT WOS:000309189101243
ER
PT J
AU Lammers, KM
Chieppa, M
Liu, L
Parent, CA
Fasano, A
AF Lammers, K. M.
Chieppa, M.
Liu, L.
Parent, C. A.
Fasano, A.
TI Neutrophils are rapidly recruited by PT-gliadin itself
SO IMMUNOLOGY
LA English
DT Meeting Abstract
CT European Congress of Immunology
CY SEP 05-08, 2012
CL Glasgow, SCOTLAND
C1 [Lammers, K. M.; Fasano, A.] Univ Maryland, Sch Med, Mucosal Biol Res Ctr, Baltimore, MD 21201 USA.
[Chieppa, M.] NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Liu, L.; Parent, C. A.] NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0019-2805
J9 IMMUNOLOGY
JI Immunology
PD SEP
PY 2012
VL 137
SU 1
SI SI
BP 218
EP 218
PG 1
WC Immunology
SC Immunology
GA 011TW
UT WOS:000309189101259
ER
PT J
AU Kelada, S
Sethupathy, P
Okoye, I
Belkaid, Y
Porcella, S
Czeiso, S
Wynn, T
Wilson, M
AF Kelada, S.
Sethupathy, P.
Okoye, I.
Belkaid, Y.
Porcella, S.
Czeiso, S.
Wynn, T.
Wilson, M.
TI miR-182 and miR-10a are key regulators of treg specialisation and
function during Th2 and Th1-associated inflammation
SO IMMUNOLOGY
LA English
DT Meeting Abstract
CT European Congress of Immunology
CY SEP 05-08, 2012
CL Glasgow, SCOTLAND
C1 [Kelada, S.; Sethupathy, P.] NIH, Ctr Human Genome, Bethesda, MD 20892 USA.
[Okoye, I.; Czeiso, S.; Wilson, M.] MRC Natl Inst Med Res, London, England.
[Belkaid, Y.; Porcella, S.; Wynn, T.] NIH, LPD, Bethesda, MD 20892 USA.
OI Kelada, Samir/0000-0003-2676-9232
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 0019-2805
J9 IMMUNOLOGY
JI Immunology
PD SEP
PY 2012
VL 137
SU 1
SI SI
BP 226
EP 226
PG 1
WC Immunology
SC Immunology
GA 011TW
UT WOS:000309189101278
ER
PT J
AU Deban, L
Gibbons, DL
Abeler-Dorner, L
Raine, T
Hwang, IY
Jandke, A
Wencker, M
Irving, PM
Kehrl, JH
Hayday, AC
AF Deban, L.
Gibbons, D. L.
Abeler-Doerner, L.
Raine, T.
Hwang, I. Y.
Jandke, A.
Wencker, M.
Irving, P. M.
Kehrl, J. H.
Hayday, A. C.
TI RGS-1 in intestinal T cell trafficking and responsiveness
SO IMMUNOLOGY
LA English
DT Meeting Abstract
CT European Congress of Immunology
CY SEP 05-08, 2012
CL Glasgow, SCOTLAND
C1 [Deban, L.; Jandke, A.; Wencker, M.] Canc Res UK, Immunosurveillance Lab, London, England.
[Gibbons, D. L.; Abeler-Doerner, L.; Hayday, A. C.] Kings Coll London, Peter Gorer Dept Immunobiol, London WC2R 2LS, England.
[Raine, T.] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England.
[Hwang, I. Y.; Kehrl, J. H.] NIAID, Cell Mol Immunol Sect B, Bethesda, MD 20892 USA.
[Irving, P. M.] Biomed Res Ctr, Natl Inst Hlth Res, London, England.
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 0019-2805
J9 IMMUNOLOGY
JI Immunology
PD SEP
PY 2012
VL 137
SU 1
SI SI
BP 386
EP 386
PG 1
WC Immunology
SC Immunology
GA 011TW
UT WOS:000309189103038
ER
PT J
AU Leboeuf, D
Hennion-Tscheltzoff, O
Gauthier, SD
Mackall, CL
Guimond, M
AF Leboeuf, D.
Hennion-Tscheltzoff, O.
Gauthier, S. D.
Mackall, C. L.
Guimond, M.
TI TCR triggering controls IL7 responsiveness and homeostatic expansion of
CD4+T cells during IL7 therapy
SO IMMUNOLOGY
LA English
DT Meeting Abstract
CT European Congress of Immunology
CY SEP 05-08, 2012
CL Glasgow, SCOTLAND
C1 [Leboeuf, D.; Hennion-Tscheltzoff, O.; Gauthier, S. D.; Guimond, M.] Maisonneuve Rosemont Hosp, Res Ctr, Montreal, PQ, Canada.
[Mackall, C. L.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 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 0019-2805
J9 IMMUNOLOGY
JI Immunology
PD SEP
PY 2012
VL 137
SU 1
SI SI
BP 430
EP 430
PG 1
WC Immunology
SC Immunology
GA 011TW
UT WOS:000309189103158
ER
PT J
AU Carregaro, V
Lima, D
Costa, D
Oliveira, C
Milanezi, C
Valenzuela, J
Ribeiro, JM
Cunha, F
Silva, J
AF Carregaro, V.
Lima-Junior, D.
Costa, D.
Oliveira, C.
Milanezi, C.
Valenzuela, J.
Ribeiro, J. M.
Cunha, F.
Silva, J.
TI Nucleosides from phlebotomus papatasi salivary gland exacerbate
leishmaniasis by generating tolerogenic dendritic cells-dependent treg
SO IMMUNOLOGY
LA English
DT Meeting Abstract
CT European Congress of Immunology
CY SEP 05-08, 2012
CL Glasgow, SCOTLAND
C1 [Carregaro, V.; Lima-Junior, D.; Costa, D.; Milanezi, C.; Cunha, F.; Silva, J.] Univ Sao Paulo, Fac Med Ribeirao Preto, BR-14049 Ribeirao Preto, Brazil.
[Oliveira, C.] Univ Fed Triangulo Mineiro, Inst Biol & Nat Sci, Uberaba, Brazil.
[Valenzuela, J.; Ribeiro, J. M.] NIAID, NIH, Sect Vector Biol, Bethesda, MD 20892 USA.
[Valenzuela, J.; Ribeiro, J. M.] Vector Mol Biol Unit, Lab Malaria & Vector Res, Bethesda, MD USA.
OI Souza Lima Junior, Djalma/0000-0002-2092-8047
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 0019-2805
J9 IMMUNOLOGY
JI Immunology
PD SEP
PY 2012
VL 137
SU 1
SI SI
BP 561
EP 561
PG 1
WC Immunology
SC Immunology
GA 011TW
UT WOS:000309189104268
ER
PT J
AU Mahony, R
Maraia, RJ
Jefferies, CA
AF Mahony, R.
Maraia, R. J.
Jefferies, C. A.
TI A role for the autoantigen La in the regulation of IFN production and
progression of SLE?
SO IMMUNOLOGY
LA English
DT Meeting Abstract
CT European Congress of Immunology
CY SEP 05-08, 2012
CL Glasgow, SCOTLAND
C1 [Mahony, R.; Jefferies, C. A.] Royal Coll Surgeons Ireland, Dublin 2, Ireland.
[Maraia, R. J.] NICHHD, NIH, Bethesda, MD 20892 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 0019-2805
J9 IMMUNOLOGY
JI Immunology
PD SEP
PY 2012
VL 137
SU 1
SI SI
BP 571
EP 572
PG 2
WC Immunology
SC Immunology
GA 011TW
UT WOS:000309189105020
ER
PT J
AU Garcia, GR
Ribeiro, JM
Maruyama, SR
Gardinassi, LG
Nelson, K
Rossi, D
Ferreira, BR
Galvao, FC
Zanelli, CF
Valentini, SR
Maia, AM
Santos, IKFD
AF Garcia, G. R.
Ribeiro, J. M.
Maruyama, S. R.
Gardinassi, L. G.
Nelson, K.
Rossi, D.
Ferreira, B. R.
Galvao, F. C.
Zanelli, C. F.
Valentini, S. R.
Maia, A. M.
de Miranda Santos, I. K. F.
TI Identification of new antigens from Rhipicephalus microplus ticks
associated to infestation phenotypes of susceptibility or resistance in
bovine hosts
SO IMMUNOLOGY
LA English
DT Meeting Abstract
CT European Congress of Immunology
CY SEP 05-08, 2012
CL Glasgow, SCOTLAND
C1 [Garcia, G. R.; Maruyama, S. R.; Gardinassi, L. G.; de Miranda Santos, I. K. F.] Univ Sao Paulo, Med Sch Ribeirao Preto, BR-14049 Ribeirao Preto, Brazil.
[Ribeiro, J. M.] NIAID, NIH USA, Rockville, MD USA.
[Nelson, K.] Virginia Commonwealth Univ, Ctr Study Biol Complex, Richmond, VA USA.
[Rossi, D.; Galvao, F. C.; Zanelli, C. F.; Valentini, S. R.] Sao Paulo State Univ, Sch Pharmaceut Sci, Araraquara, Brazil.
[Ferreira, B. R.] Univ Sao Paulo, Ribeirao Preto Sch Nursing, BR-14049 Ribeirao Preto, Brazil.
[Maia, A. M.] Univ Sao Paulo, Sch Anim Sci & Food Technol, Pirassununga, Brazil.
RI de Miranda Santos, Isabel/B-7597-2012; zanelli, cleslei/C-1916-2013;
Garcia, Gustavo/E-5182-2013; Ferreira, Beatriz/C-2003-2012; de Miranda
Santos, Isabel/D-5261-2016
OI de Miranda Santos, Isabel/0000-0002-0438-4430; Ferreira,
Beatriz/0000-0002-6781-2236;
NR 0
TC 0
Z9 0
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0019-2805
J9 IMMUNOLOGY
JI Immunology
PD SEP
PY 2012
VL 137
SU 1
SI SI
BP 627
EP 627
PG 1
WC Immunology
SC Immunology
GA 011TW
UT WOS:000309189105176
ER
PT J
AU Tosi, G
Forlani, G
Andresen, V
Turci, M
Bertazzoni, U
Franchini, G
Accolla, R
AF Tosi, G.
Forlani, G.
Andresen, V.
Turci, M.
Bertazzoni, U.
Franchini, G.
Accolla, R.
TI Human oncogenic retrovirus HTLV-1 replication is suppressed by the MHC
class II transcriptional activator CIITA via an inhibitory action on the
viral transactivator Tax-1
SO IMMUNOLOGY
LA English
DT Meeting Abstract
CT European Congress of Immunology
CY SEP 05-08, 2012
CL Glasgow, SCOTLAND
C1 [Andresen, V.] Inst Med, Hematol Sect, Bergen, Norway.
[Turci, M.; Bertazzoni, U.] Dept Life & Reprod Sci, Sect Biol & Genet, Verona, Italy.
[Franchini, G.] NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0019-2805
J9 IMMUNOLOGY
JI Immunology
PD SEP
PY 2012
VL 137
SU 1
SI SI
BP 639
EP 639
PG 1
WC Immunology
SC Immunology
GA 011TW
UT WOS:000309189105211
ER
PT J
AU Cohen, CJ
Horovitz-Fried, M
Morgan, RA
Goldstein, R
Daniel-Meshulam, I
AF Cohen, C. J.
Horovitz-Fried, M.
Morgan, R. A.
Goldstein, R.
Daniel-Meshulam, I.
TI 4-1BB engineered human T-cells demonstrate enhanced function and mediate
regression of established melanoma tumors
SO IMMUNOLOGY
LA English
DT Meeting Abstract
CT European Congress of Immunology
CY SEP 05-08, 2012
CL Glasgow, SCOTLAND
C1 [Cohen, C. J.; Horovitz-Fried, M.; Goldstein, R.; Daniel-Meshulam, I.] Bar Ilan Univ, Fac Life Sci, Ramat Gan, Israel.
[Morgan, R. A.] NCI, Surg Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0019-2805
J9 IMMUNOLOGY
JI Immunology
PD SEP
PY 2012
VL 137
SU 1
SI SI
BP 678
EP 678
PG 1
WC Immunology
SC Immunology
GA 011TW
UT WOS:000309189106043
ER
PT J
AU Mourin, G
Appay, V
Iglesias, MC
Fastenackels, S
Autran, B
Sauce, D
Price, D
Almeida, J
Stern, M
Roux, A
AF Mourin, G.
Appay, V.
Iglesias, M. C.
Fastenackels, S.
Autran, B.
Sauce, D.
Price, D.
Almeida, J.
Stern, M.
Roux, A.
TI CMV-specific CD8+T-cell immunity is a co-factor for acute rejection in
lung transplantation
SO IMMUNOLOGY
LA English
DT Meeting Abstract
CT European Congress of Immunology
CY SEP 05-08, 2012
CL Glasgow, SCOTLAND
C1 [Mourin, G.; Appay, V.; Iglesias, M. C.; Fastenackels, S.; Sauce, D.; Roux, A.] INSERM, UMR S 945, Paris, France.
[Autran, B.] Grp Hosp Pitie Salpetriere, AP HP, Lab Immunol Cellulaire & Tissulaire, F-75634 Paris, France.
[Price, D.] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff, S Glam, Wales.
[Almeida, J.] NIH, Human Immunol Sect, Bethesda, MD 20892 USA.
[Stern, M.] Hop Foch, Serv Pneumol, Suresnes, France.
RI Price, David/C-7876-2013; sauce, delphine/H-1990-2014
OI Price, David/0000-0001-9416-2737; sauce, delphine/0000-0003-4596-7373
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 0019-2805
J9 IMMUNOLOGY
JI Immunology
PD SEP
PY 2012
VL 137
SU 1
SI SI
BP 738
EP 738
PG 1
WC Immunology
SC Immunology
GA 011TW
UT WOS:000309189106207
ER
PT J
AU Massa, C
Thomas, C
Wang, E
Marincola, F
Seliger, B
AF Massa, C.
Thomas, C.
Wang, E.
Marincola, F.
Seliger, B.
TI 'Omic'-based comparison of different formulation of vaccine DC
SO IMMUNOLOGY
LA English
DT Meeting Abstract
CT European Congress of Immunology
CY SEP 05-08, 2012
CL Glasgow, SCOTLAND
C1 [Massa, C.; Thomas, C.; Seliger, B.] Univ Halle Wittenberg, Inst Med Immunol, Halle, Saale, Germany.
[Wang, E.; Marincola, F.] NIH, Dept Transfus, Med Clin Ctr, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0019-2805
J9 IMMUNOLOGY
JI Immunology
PD SEP
PY 2012
VL 137
SU 1
SI SI
BP 753
EP 753
PG 1
WC Immunology
SC Immunology
GA 011TW
UT WOS:000309189106244
ER
PT J
AU Sullivan, N
Asiedu, C
Baily, M
Stanley, D
AF Sullivan, N.
Asiedu, C.
Baily, M.
Stanley, D.
TI Identification and generation of CD8 T-cell subsets required for vaccine
protection against Ebolavirus
SO IMMUNOLOGY
LA English
DT Meeting Abstract
CT European Congress of Immunology
CY SEP 05-08, 2012
CL Glasgow, SCOTLAND
C1 [Sullivan, N.; Asiedu, C.; Stanley, D.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
[Baily, M.] NIAID, NIH, Ft Belvior, VA 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 0019-2805
J9 IMMUNOLOGY
JI Immunology
PD SEP
PY 2012
VL 137
SU 1
SI SI
BP 761
EP 761
PG 1
WC Immunology
SC Immunology
GA 011TW
UT WOS:000309189106268
ER
PT J
AU Doubeni, CA
Major, JM
Laiyemo, AO
Schootman, M
Zauber, AG
Hollenbeck, AR
Sinha, R
Allison, J
AF Doubeni, Chyke A.
Major, Jacqueline M.
Laiyemo, Adeyinka O.
Schootman, Mario
Zauber, Ann G.
Hollenbeck, Albert R.
Sinha, Rashmi
Allison, Jeroan
TI Contribution of Behavioral Risk Factors and Obesity to Socioeconomic
Differences in Colorectal Cancer Incidence
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID HEALTH-AMERICAN-ASSOCIATION; RETIRED-PERSONS DIET; PHYSICAL-ACTIVITY;
NATIONAL-INSTITUTES; UNITED-STATES; MEDICARE ENROLLEES; COLON-CANCER;
PREVENTION; MORTALITY; INDEX
AB Health behaviors are known risk factors for colorectal cancer and are more common in low socioeconomic status (SES) populations. We evaluated the extent to which behavioral risk factors and body mass index (BMI) explain SES disparities in colorectal cancer incidence, overall and by tumor location.
We analyzed prospective National Institutes of Health-AARP Diet and Health Study data on 506 488 participants who were recruited in 19951996 from six US states and two metropolitan areas and followed through 2006. Detailed baseline data on risk factors for colorectal cancer, including health behaviors, were obtained using questionnaires. SES was measured by self-reported education and census-tract data. The outcome was primary incident invasive colorectal adenocarcinoma. Poisson regression was used to estimate the association between SES and risk of incident colorectal cancer, with adjustment for age, sex, race and ethnicity, family history, and state of residence. The model estimates were used to derive percentage mediation by behavioral risk factors; bias-corrected 95% confidence intervals were obtained through bootstrap techniques.
Seven-thousand six-hundred seventy-six participants developed colorectal cancer during follow-up. SES differences in prevalence of physical inactivity, unhealthy diet, smoking, and unhealthy weight each explained between 11.3% (BMI) and 21.6% (diet) of the association between education and risk of colorectal cancer and between 8.6% (smoking) and 15.3% (diet) of the association between neighborhood SES and risk of colorectal cancer. Health behaviors and BMI combined explained approximately 43.9% (95% CI 35.1% to 57.9%) of the association of education and 36.2% (95% CI 28.0% to 51.2%) of the association of neighborhood SES with risk of colorectal cancer. The percentage explained by all factors and BMI combined was largest for right colon cancers and smallest for rectal cancers.
A substantial proportion of the socioeconomic disparity in risk of new-onset colorectal cancer, and particularly of right colon cancers, may be attributable to the higher prevalence of adverse health behaviors in low-SES populations.
C1 [Doubeni, Chyke A.] Univ Penn, Dept Family Med & Community Hlth, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Doubeni, Chyke A.; Allison, Jeroan] Univ Massachusetts, Sch Med, Dept Family Med & Community Hlth, Worcester, MA USA.
[Major, Jacqueline M.; Sinha, Rashmi] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Laiyemo, Adeyinka O.] Howard Univ, Dept Med, Washington, DC 20059 USA.
[Schootman, Mario] Washington Univ, Sch Med, Dept Med, Div Hlth Behav Res, St Louis, MO 63110 USA.
[Zauber, Ann G.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
[Hollenbeck, Albert R.] AARP, Washington, DC USA.
RP Doubeni, CA (reprint author), Univ Penn, Dept Family Med & Community Hlth, Perelman Sch Med, 2 Gates,3400 Spruce St, Philadelphia, PA 19104 USA.
EM Chyke.Doubeni@uphs.upenn.edu
OI Doubeni, Chyke/0000-0001-7495-0285; Schootman,
Mario/0000-0003-1162-8824; Allison, Jeroan/0000-0003-4472-2112
FU National Cancer Institute at the National Institutes of Health
[K01CA127118, U01 CA151736, U54CA091431-09S1, R01 CA137750]; Florida
Department of Health (FDOH)
FX This report was supported in part by awards from the National Cancer
Institute at the National Institutes of Health (K01CA127118 and U01
CA151736 to CAD, U54CA091431-09S1 to AOL, and R01 CA137750 to MS). This
analysis was conducted in collaboration with intramural scientists at
the National Cancer Institute, who participated in the analysis and
interpretation of the data, the writing of the manuscript, and the
decision to submit it for publication. However, the contents of this
report are solely the responsibility of the authors and do not
necessarily represent the official views of the National Institutes of
Health or the National Cancer Institute. The authors have no conflicts
of interest.; 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.
Cancer incidence data from California were collected by the California
Department of Health Services, Cancer Surveillance Section. Cancer
incidence data from the Detroit metropolitan area were collected by the
Michigan Cancer Surveillance Program, Community Health Administration,
State of Michigan. The Florida cancer incidence data used in this report
were collected by the Florida Cancer Data System (FCDC) under contract
with the Florida Department of Health (FDOH). 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 Medical Center
in New Orleans. Cancer incidence data from New Jersey were collected by
the New Jersey State Cancer Registry, Cancer Epidemiology Services, New
Jersey State Department of Health and Senior Services. Cancer incidence
data from North Carolina were collected by the North Carolina Central
Cancer Registry. 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. Cancer
incidence data from Texas were collected by the Texas Cancer Registry,
Cancer Epidemiology and Surveillance Branch, Texas Department of State
Health Services.
NR 42
TC 39
Z9 40
U1 1
U2 22
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 2012
VL 104
IS 18
BP 1353
EP 1362
DI 10.1093/jnci/djs346
PG 10
WC Oncology
SC Oncology
GA 010ZG
UT WOS:000309132500006
PM 22952311
ER
PT J
AU Xu, FH
Xiong, D
Xu, YF
Cao, SM
Xue, WQ
Qin, HD
Liu, WS
Cao, JY
Zhang, Y
Feng, QS
Chen, LZ
Li, MZ
Liu, ZW
Liu, Q
Hong, MH
Shugart, YY
Zeng, YX
Zeng, MS
Jia, WH
AF Xu, Feng-Hua
Xiong, Dan
Xu, Ya-Fei
Cao, Su-Mei
Xue, Wen-Qiong
Qin, Hai-De
Liu, Wen-Sheng
Cao, Jing-Yan
Zhang, Ying
Feng, Qi-Sheng
Chen, Li-Zhen
Li, Man-Zhi
Liu, Zhi-Wei
Liu, Qing
Hong, Ming-Huang
Shugart, Yin Yao
Zeng, Yi-Xin
Zeng, Mu-Sheng
Jia, Wei-Hua
TI An Epidemiological and Molecular Study of the Relationship Between
Smoking, Risk of Nasopharyngeal Carcinoma, and EpsteinBarr Virus
Activation
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID LINKED-IMMUNOSORBENT-ASSAY; ANTIBODY-POSITIVE PERSONS; SQUAMOUS-CELL
CARCINOMA; BARR-VIRUS; CIGARETTE-SMOKING; EPITHELIAL-CELLS;
UNITED-STATES; LUNG-CANCER; CAPSID ANTIGEN; TOBACCO-SMOKE
AB Elevated levels of antibodies against antigens in the EpsteinBarr virus (EBV) lytic phase are important predictive markers for nasopharyngeal carcinoma (NPC) risk. Several lifestyle factors, including smoking, have also been associated with NPC risk. We hypothesized that some specific lifestyle factors induce transformation of EBV from the latent to the lytic stage and contribute to NPC occurrence.
We conducted a casecontrol study using data from male case patients (n = 1316) and control subjects (n = 1571) living in Guangdong Province, an area in China at high risk for NPC, to study potential NPC risk factors and EBV inducers. Two independent healthy male populations from a second high-risk area (n = 1657) and a low-risk area (n = 1961) were also included in the analysis of potential EBV inducers using logistic regression models. In vitro assays were performed to investigate the effect of cigarette smoke extract on EBV activation in two EBV-positive cell lines. All statistical tests were two-sided.
Smoking was associated with an increased risk of NPC among the Guangdong participants with 2040 and 40 or more pack-years vs never smokers (OR = 1.52, 95% CI = 1.22 to 1.88 and OR = 1.76, 95% CI = 1.34 to 2.32, respectively; P-trend < .001). Smoking was the only factor linked to EBV seropositivity among the expanded control group and the independent low-risk population. In vitro experiments showed that cigarette smoke extract promoted EBV replication, induced the expression of the immediate-early transcriptional activators Zta and Rta, and increased transcriptional expression levels of BFRF3 and gp350 in the lytic phase.
Smoking is not only associated with NPC risk in individuals from China but is also associated with EBV seropositivity in healthy males and is involved in EBV activation.
C1 [Xu, Feng-Hua; Xiong, Dan; Xu, Ya-Fei; Xue, Wen-Qiong; Qin, Hai-De; Liu, Wen-Sheng; Cao, Jing-Yan; Zhang, Ying; Feng, Qi-Sheng; Li, Man-Zhi; Liu, Zhi-Wei; Zeng, Yi-Xin; Zeng, Mu-Sheng; Jia, Wei-Hua] Sun Yat Sen Univ, Ctr Canc, Dept Expt Res, State Key Lab Oncol S China, Guangzhou 510060, Guangdong, Peoples R China.
[Xu, Feng-Hua; Jia, Wei-Hua] Sun Yat Sen Univ, Dept Med Stat & Epidemiol, Sch Publ Hlth, Guangzhou 510060, Guangdong, Peoples R China.
[Cao, Su-Mei; Liu, Qing; Hong, Ming-Huang] Sun Yat Sen Univ, Ctr Canc, Clin Trials Ctr, State Key Lab Oncol S China, Guangzhou 510060, Guangdong, Peoples R China.
[Cao, Su-Mei; Liu, Qing; Hong, Ming-Huang] Sun Yat Sen Univ, Ctr Canc, Inst Drug Clin Trials, Guangzhou 510060, Guangdong, Peoples R China.
[Shugart, Yin Yao] NIMH, Unit Stat Genom, Div Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Jia, WH (reprint author), Sun Yat Sen Univ, Ctr Canc, Dept Expt Res, State Key Lab Oncol S China, 651 Dongfeng Rd E, Guangzhou 510060, Guangdong, Peoples R China.
EM zengmsh@mail.sysu.edu.cn; jiawh@sys-ucc.org.cn
FU Ministry of Science and Technology of China [2011CB504300,
2011ZX09307-001-04]; National Natural Science Funds for Distinguished
Young Scholar [81025014]; National Natural Science Foundation of China
[81000925]; Guangdong Department of Science and Technology
[2008A060201009]
FX Ministry of Science and Technology of China (2011CB504300;
2011ZX09307-001-04), National Natural Science Funds for Distinguished
Young Scholar (81025014), the National Natural Science Foundation of
China (81000925), and Guangdong Department of Science and Technology
(2008A060201009).
NR 83
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U1 1
U2 18
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 2012
VL 104
IS 18
BP 1396
EP 1410
DI 10.1093/jnci/djs320
PG 15
WC Oncology
SC Oncology
GA 010ZG
UT WOS:000309132500010
PM 22972969
ER
PT J
AU Castle, PE
Glass, AG
Rush, BB
Scott, DR
Wentzensen, N
Gage, JC
Buckland, J
Rydzak, G
Lorincz, AT
Wacholder, S
AF Castle, Philip E.
Glass, Andrew G.
Rush, Brenda B.
Scott, David R.
Wentzensen, Nicolas
Gage, Julia C.
Buckland, Julie
Rydzak, Greg
Lorincz, Attila T.
Wacholder, Sholom
TI Clinical Human Papillomavirus Detection Forecasts Cervical Cancer Risk
in Women Over 18 Years of Follow-Up
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; NEOPLASIA GRADE 3; ASC-US CYTOLOGY;
INTRAEPITHELIAL NEOPLASIA; CONVENTIONAL CYTOLOGY; INCIDENCE TRENDS;
UNITED-STATES; HPV TYPE-16; DNA; ADENOCARCINOMA
AB Purpose
To describe the long-term (>= 10 years) benefits of clinical human papillomavirus (HPV) DNA testing for cervical precancer and cancer risk prediction.
Methods
Cervicovaginal lavages collected from 19,512 women attending a health maintenance program were retrospectively tested for HPV using a clinical test. HPV positives were tested for HPV16 and HPV18 individually using a research test. A Papanicolaou (Pap) result classified as atypical squamous cells of undetermined significance (ASC-US) or more severe was considered abnormal. Women underwent follow-up prospectively with routine annual Pap testing up to 18 years. Cumulative incidence rates (CIRs) of >= grade 3 cervical intraepithelial neoplasia (CIN3+) or cancer for enrollment test results were calculated.
Results
A baseline negative HPV test provided greater reassurance against CIN3+ over the 18-year follow-up than a normal Pap (CIR, 0.90% v 1.27%). Although both baseline Pap and HPV tests predicted who would develop CIN3+ within the first 2 years of follow-up, only HPV testing predicted who would develop CIN3+ 10 to 18 years later (P = .004). HPV16- and HPV18-positive women with normal Pap were at elevated risk of CIN3+ compared with other HPV-positive women with normal Pap and were at similar risk of CIN3+ compared with women with a low-grade squamous intraepithelial Pap.
Conclusion
HPV testing to rule out cervical disease followed by Pap testing and possibly combined with the detection of HPV16 and HPV18 among HPV positives to identify those at immediate risk of CIN3+ would be an efficient algorithm for cervical cancer screening, especially in women age 30 years or older. J Clin Oncol 30:3044-3050. (C) 2012 by American Society of Clinical Oncology
C1 [Castle, Philip E.] Amer Soc Clin Pathologists, Washington, DC 20005 USA.
[Glass, Andrew G.; Rush, Brenda B.; Scott, David R.] Kaiser Permanente Ctr Hlth Res, Portland, OR USA.
[Wentzensen, Nicolas; Gage, Julia C.; Wacholder, Sholom] NCI, NIH, Bethesda, MD 20892 USA.
[Buckland, Julie; Rydzak, Greg] Informat Management Serv Inc, Silver Spring, MD USA.
[Lorincz, Attila T.] Queen Mary Univ London, Wolfson Inst Prevent Med, London, England.
RP Castle, PE (reprint author), Amer Soc Clin Pathologists, 1225 New York Ave NW,Suite 350, Washington, DC 20005 USA.
EM philip.castle@ascp.org
FU Intramural Research Program of the National Cancer Institute, National
Institutes of Health, Bethesda, MD; Qiagen
FX Supported in part by the Intramural Research Program of the National
Cancer Institute, National Institutes of Health, Bethesda, MD.; Although
all authors completed the disclosure declaration, the following
author(s) and/or an author's immediate family member(s) indicated a
financial or other interest that is relevant to the subject matter under
consideration in this article. Certain relationships marked with a "U"
are those for which no compensation was received; those relationships
marked with a "C" were compensated. For a detailed description of the
disclosure categories, or for more information about ASCO's conflict of
interest policy, please refer to the Author Disclosure Declaration and
the Disclosures of Potential Conflicts of Interest section in
Information for Contributors. Employment or Leadership Position: None
Consultant or Advisory Role: Philip E. Castle, Merck (C), Qiagen (U),
Roche (U); Attila T. Lorincz, Qiagen (C) Stock Ownership: Attila T.
Lorincz, Qiagen Honoraria: None Research Funding: Attila T. Lorincz,
Qiagen Expert Testimony: None Other Remuneration: None
NR 41
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U1 1
U2 8
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD SEP 1
PY 2012
VL 30
IS 25
BP 3044
EP 3050
DI 10.1200/JCO.2011.38.8389
PG 7
WC Oncology
SC Oncology
GA 002TM
UT WOS:000308558800008
PM 22851570
ER
PT J
AU Ito, T
Igarashi, H
Jensen, RT
AF Ito, Tetsuhide
Igarashi, Hisato
Jensen, Robert T.
TI Therapy of metastatic pancreatic neuroendocrine tumors (pNETs): recent
insights and advances
SO JOURNAL OF GASTROENTEROLOGY
LA English
DT Review
DE Neuroendocrine tumor; Pancreatic endocrine tumor; Liver metastases;
Gastrinoma; Insulinoma; Surgery; Chemotherapy; Streptozotocin;
Everolimus; Sunitinib; Somatostatin; Octreotide; Lanreotide; Hepatic
transarterial embolization; Liver transplantation; Peptide receptor
radionuclide therapy; Somatostatin receptor; SIRT; Chemoembolization;
Unresectable liver metastases
ID ENETS CONSENSUS GUIDELINES; ISLET-CELL-CARCINOMA; ENDOCRINE
GASTROENTEROPANCREATIC TUMORS; SOMATOSTATIN RECEPTOR SCINTIGRAPHY;
ZOLLINGER-ELLISON-SYNDROME; SELECTIVE INTERNAL RADIATION; GUIDED ETHANOL
ABLATION; LIVER METASTASES; PROGNOSTIC-FACTORS; LONG-TERM
AB Neuroendocrine tumors (NETs) [carcinoids, pancreatic neuroendocrine tumors (pNETs)] are becoming an increasing clinical problem because not only are they increasing in frequency, but they can frequently present with advanced disease that requires diagnostic and treatment approaches different from those used in the neoplasms that most physicians are used to seeing and treating. In the past few years there have been numerous advances in all aspects of NETs including: an understanding of their unique pathogenesis; specific classification systems developed which have prognostic value; novel methods of tumor localization developed; and novel treatment approaches described. In patients with advanced metastatic disease these include the use of newer chemotherapeutic approaches, an increased understanding of the role of surgery and cytoreductive methods, the development of methods for targeted delivery of cytotoxic agents, and the development of targeted medical therapies (everolimus, sunitinib) based on an increased understanding of the disease biology. Although pNETs and gastrointestinal NETs share many features, recent studies show they differ in pathogenesis and in many aspects of diagnosis and treatment, including their responsiveness to different therapies. Because of limited space, this review will be limited to the advances made in the management and treatment of patients with advanced metastatic pNETs over the past 5 years.
C1 [Jensen, Robert T.] NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA.
[Ito, Tetsuhide; Igarashi, Hisato] Kyushu Univ, Dept Med & Bioregulatory Sci, Grad Sch Med Sci, Higashi Ku, Fukuoka 8128582, Japan.
RP Jensen, RT (reprint author), NIDDK, Digest Dis Branch, NIH, Bldg 10,Room 9C-103, Bethesda, MD 20892 USA.
EM robertj@bdg10.niddk.nih.gov
RI U-ID, Kyushu/C-5291-2016
FU NIDDK, NIH
FX This work was partially supported by intramural funds of NIDDK, NIH.
NR 214
TC 36
Z9 36
U1 0
U2 14
PU SPRINGER JAPAN KK
PI TOKYO
PA CHIYODA FIRST BLDG EAST, 3-8-1 NISHI-KANDA, CHIYODA-KU, TOKYO, 101-0065,
JAPAN
SN 0944-1174
EI 1435-5922
J9 J GASTROENTEROL
JI J. Gastroenterol.
PD SEP
PY 2012
VL 47
IS 9
BP 941
EP 960
DI 10.1007/s00535-012-0642-8
PG 20
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 006LY
UT WOS:000308821900001
PM 22886480
ER
PT J
AU Fedorova, OV
Kashkin, VA
Zakharova, IO
Lakatta, EG
Bagrov, AY
AF Fedorova, Olga V.
Kashkin, Vladimir A.
Zakharova, Irina O.
Lakatta, Edward G.
Bagrov, Alexei Y.
TI Age-associated increase in salt sensitivity is accompanied by a shift in
the atrial natriuretic peptide modulation of the effect of
marinobufagenin on renal and vascular sodium pump
SO JOURNAL OF HYPERTENSION
LA English
DT Article
DE aging; cyclic guanosine monophosphate; dietary sodium; hypertension;
marinobufagenin; Na/K-ATPase; natriuretic peptides; protein kinase G;
salt sensitivity
ID ENDOGENOUS CARDIOTONIC STEROIDS; BLOOD-PRESSURE; NA,K-ATPASE ACTIVITY;
MONOCLONAL-ANTIBODY; DIETARY-SODIUM; NA/K-ATPASE; HYPERTENSION;
INHIBITION; RATS; PHOSPHORYLATION
AB Background: Marinobufagenin (MBG) promotes natriuresis via inhibition of renotubular Na/K-ATPase (NKA) and causes vasoconstriction via inhibition of vascular NKA. Atrial natriuretic peptide (ANP), via cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG)-dependent mechanism, sensitizes renal NKA to MBG but reduces MBG-induced inhibition of vascular NKA. As aging is associated with a downregulation of cGMP/PKG signaling, we hypothesized that in older rats, ANP would not potentiate renal effects of MBG and would not oppose vascular effects of MBG.
Methods: In younger (3-month-old) and older (12-month-old) Sprague-Dawley rats, we compared SBP, natriuresis, activity of NKA in aorta and renal medulla, and levels of MBG and alpha-ANP at baseline and following acute NaCl loading (20%, 2.5 ml/kg, intraperitoneally), and studied modulation of MBG-induced NKA inhibition by alpha-ANP in vitro.
Results: As compared with younger rats, NaCl-loaded older rats exhibited a greater MBG response, greater SBP elevation (25 vs. 10 mmHg, P < 0.01) and greater inhibition of NKA in aorta (39 vs. 7%, P < 0.01), 30% less natriuresis, and less inhibition of renal NKA (25 vs. 42%, P < 0.05) in the presence of comparable responses of alpha-ANP and cGMP. In aorta and kidney of older rats, the levels of PKG were reduced, the levels of phosphodiesterase-5 were increased compared with that in young rats, and alpha-ANP failed to modulate MBG-induced NKA inhibition.
Conclusion: Age-associated downregulation of cGMP/PKG-dependent signaling impairs the ability of ANP to modulate the effects of MBG on the sodium pump, which contributes to salt sensitivity.
C1 [Bagrov, Alexei Y.] NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Bagrov, AY (reprint author), NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM bagrova@mail.nih.gov
OI Kashkin, Vladimir/0000-0002-7202-0233
FU National Institute on Aging, NIH
FX Supported by Intramural Research Program, National Institute on Aging,
NIH. Authors gratefully acknowledge excellent technical support by
Danielle Joseph and Chad Boily.
NR 35
TC 5
Z9 5
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0263-6352
J9 J HYPERTENS
JI J. Hypertens.
PD SEP
PY 2012
VL 30
IS 9
BP 1817
EP 1826
DI 10.1097/HJH.0b013e328356399b
PG 10
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 006EF
UT WOS:000308801600020
PM 22796708
ER
PT J
AU McKee, TC
Rabe, D
Bokesch, HR
Grkovic, T
Whitson, EL
Diyabalanage, T
Van Wyk, AWW
Marcum, SR
Gardella, RS
Gustafson, KR
Linehan, WM
McMahon, JB
Bottaro, DP
AF McKee, Tawnya C.
Rabe, Daniel
Bokesch, Heidi R.
Grkovic, Tanja
Whitson, Emily L.
Diyabalanage, Thushara
Van Wyk, Albert W. W.
Marcum, Stephanie R.
Gardella, Roberta S.
Gustafson, Kirk R.
Linehan, W. Marston
McMahon, James B.
Bottaro, Donald P.
TI Inhibition of Hypoxia Inducible Factor-2 Transcription: Isolation of
Active Modulators from Marine Sponges
SO JOURNAL OF NATURAL PRODUCTS
LA English
DT Article
ID STREPTOMYCES-LAVENDULAE; TUMOR-GROWTH; HALICLONA SP; STEREOCHEMISTRY;
HETERONEMIN; PUUPEHENONE; MIMOSAMYCIN; METABOLITES; SUFFICIENT;
SUBSTANCE
AB Renal or kidney cancer accounts for about 3% of all cancer cases reported each year in the U.S. Molecular signatures that define the cancer, such as the loss of functional VHL, are found in both sporadic and familial cases of cancer. In clear cell renal cancer, the transcription factor HIF-2 alpha has been shown to have a distinct role in tumorigenesis. Our laboratories developed a cell-based screen to identify modulators of HIF-2 alpha. Screening of the NCI's Natural Product Extract Repository resulted in the identification of 10 sponge extracts, from which 12 compounds were isolated. The biological evaluation of these compounds will be discussed including evaluation of HIF-1 alpha vs HIF-2 alpha selectivity and the isolated compounds' effects on mRNA from several pathways regulated by HIF.
C1 [McKee, Tawnya C.; Bokesch, Heidi R.; Grkovic, Tanja; Whitson, Emily L.; Diyabalanage, Thushara; Van Wyk, Albert W. W.; Marcum, Stephanie R.; Gardella, Roberta S.; Gustafson, Kirk R.; McMahon, James B.] Ctr Canc Res, Mol Targets Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Rabe, Daniel; Linehan, W. Marston; Bottaro, Donald P.] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Bokesch, Heidi R.] SAIC Frederick Inc, Frederick, MD 21702 USA.
RP McKee, TC (reprint author), Ctr Canc Res, Mol Targets Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
EM mckeeta@mail.nih.gov
RI Grkovic, Tanja/B-8874-2012; Bottaro, Donald/F-8550-2010
OI Bottaro, Donald/0000-0002-5057-5334
FU Molecular Targets Laboratory; Urologic Oncology Branch, Intramural
Research Program of NIH, National Cancer Institute, Center for Cancer
Research; National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This project has been supported in part by the Molecular Targets
Laboratory and the Urologic Oncology Branch, Intramural Research Program
of NIH, National Cancer Institute, Center for Cancer Research, and 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 SK-RC-28
cells were generously provided by L. Old (Ludwig Institute for Cancer
Research), and the RCC4 cells were generously provided by K. Kok
(University of Groningen).
NR 28
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U1 2
U2 23
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0163-3864
J9 J NAT PROD
JI J. Nat. Prod.
PD SEP
PY 2012
VL 75
IS 9
BP 1632
EP 1636
DI 10.1021/np300211x
PG 5
WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy
GA 011XO
UT WOS:000309199800018
PM 22928967
ER
PT J
AU Kiyatkin, EA
Lenoir, M
AF Kiyatkin, Eugene A.
Lenoir, Magalie
TI Rapid fluctuations in extracellular brain glucose levels induced by
natural arousing stimuli and intravenous cocaine: fueling the brain
during neural activation
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
DE amperometry; enzyme-based sensors; cerebral blood flow; arousal;
neuronal activation
ID CEREBRAL-BLOOD-FLOW; FREELY MOVING RATS; STRIATAL NEURONAL-ACTIVITY;
PARS-RETICULATA NEURONS; NUCLEUS-ACCUMBENS; SUBSTANTIA-NIGRA;
UNRESTRAINED RATS; EEG DESYNCHRONIZATION; DOPAMINE RELEASE; AWAKE
AB Kiyatkin EA, Lenoir M. Rapid fluctuations in extracellular brain glucose levels induced by natural arousing stimuli and intravenous cocaine: fueling the brain during neural activation. J Neurophysiol 108: 1669-1684, 2012. First published June 20, 2012; doi: 10.1152/jn.00521.2012.-Glucose, a primary energetic substrate for neural activity, is continuously influenced by two opposing forces that tend to either decrease its extracellular levels due to enhanced utilization in neural cells or increase its levels due to entry from peripheral circulation via enhanced cerebral blood flow. How this balance is maintained under physiological conditions and changed during neural activation remains unclear. To clarify this issue, enzyme-based glucose sensors coupled with high-speed amperometry were used in freely moving rats to evaluate fluctuations in extracellular glucose levels induced by brief audio stimulus, tail pinch (TP), social interaction with another rat (SI), and intravenous cocaine (1 mg/kg). Measurements were performed in nucleus accumbens (NAcc) and substantia nigra pars reticulata (SNr), which drastically differ in neuronal activity. In NAcc, where most cells are powerfully excited after salient stimulation, glucose levels rapidly (latency 2-6 s) increased (30-70 mu M or 6-14% over baseline) by all stimuli; the increase differed in magnitude and duration for each stimulus. In SNr, where most cells are transiently inhibited by salient stimuli, TP, SI, and cocaine induced a biphasic glucose response, with the initial decrease (-20-40 mu M or 5-10% below baseline) followed by a reboundlike increase. The critical role of neuronal activity in mediating the initial glucose response was confirmed by monitoring glucose currents after local microinjections of glutamate (GLU) or procaine (PRO). While intra-NAcc injection of GLU transiently increased glucose levels in this structure, intra-SNr PRO injection resulted in rapid, transient decreases in SNr glucose. Therefore, extracellular glucose levels in the brain change very rapidly after physiological and pharmacological stimulation, the response is structure specific, and the pattern of neuronal activity appears to be a critical factor determining direction and magnitude of physiological fluctuations in glucose levels.
C1 [Kiyatkin, Eugene A.] NIDA, In Vivo Electrophysiol Unit, Behav Neurosci Branch, Intramural Res Program,NIH,DHHS, Baltimore, MD 21224 USA.
RP Kiyatkin, EA (reprint author), NIDA, In Vivo Electrophysiol Unit, Behav Neurosci Branch, Intramural Res Program,NIH,DHHS, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM ekiyatki@intra.nida.nih.gov
FU Intramural Research Program of the National Institute on Drug Abuse
FX This study was supported by the Intramural Research Program of the
National Institute on Drug Abuse.
NR 61
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U1 0
U2 4
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD SEP
PY 2012
VL 108
IS 6
BP 1669
EP 1684
DI 10.1152/jn.00521.2012
PG 16
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 009BK
UT WOS:000309000100012
PM 22723672
ER
PT J
AU Theodore, WH
Martinez, AR
Khan, OI
Liew, CJ
Auh, S
Dustin, IM
Heiss, J
Sato, S
AF Theodore, William H.
Martinez, Ashley R.
Khan, Omar I.
Liew, Clarissa J.
Auh, Sungyoung
Dustin, Irene M.
Heiss, John
Sato, Susumu
TI PET of Serotonin 1A Receptors and Cerebral Glucose Metabolism for
Temporal Lobectomy
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Article
DE glucose metabolism; positron emission tomography; serotonin receptors;
temporal lobe epilepsy
ID LOBE EPILEPSY SURGERY; POSITRON-EMISSION-TOMOGRAPHY; 5-HT1A RECEPTORS;
WHITE-MATTER; F-18-FDG PET; NORMAL MRI; BINDING; PREDICTORS;
ABNORMALITIES; INCREASES
AB The objective of this study was to compare 5-hydroxytryptamine receptor 1A (5-HT1A) PET with cerebral metabolic rate of glucose (CMRgIc) PET for temporal lobectomy planning. Methods: We estimated 5-HT1A receptor binding preoperatively with F-18-trans-4-fluoro-N-2-[4-(2-methoxyphenyl) piperazin-1-yl]ethyl-N-(2-pyridyl) cyclohexane carboxamide (F-18-FCWAY) PET and CMRgIc measurement with F-18-FDG in regions drawn on coregistered MRI after partial-volume correction in 41 patients who had anterior temporal lobectomy with at least a 1-y follow-up. Surgery was tailored to individual preresection evaluations and intraoperative electrocorticography. Mean regional asymmetry values and the number of regions with asymmetry exceeding 2 SDs in 16 healthy volunteers were compared between seizure-free and non-seizure-free patients. F-18-FCWAY but not F-18-FDG and MRI data were masked for surgical decisions and outcome assessment. Results: Twenty-six of 41 (63%) patients seizure-free since surgery had significantly different mesial temporal asymmetries, compared with 15 non-seizure-free patients for both F-18-FCWAY (F-1.39 = 5.87; P = 0.02) and F-18-FDG PET (F-1.38 = 5.79; P = 0.021). The probability of being seizure-free was explained by both F-18-FDG and F-18-FCWAY PET, but not MRI, with a significant additional F-18-FCWAY effect (chi(2)(2) = 9.8796; P = 0.0072) after the probability of being seizure-free was explained by F-18-FDG. Although MRI alone was not predictive, any combination of 2 lateralizing imaging studies was highly predictive of seizure freedom. Conclusion: Our study provides class III evidence that both 5-HT1A receptor PET and CMRgIc PET can contribute to temporal lobectomy planning. Additional studies should explore the potential for temporal lobectomy based on interictal electroencephalography and minimally invasive imaging studies.
C1 [Theodore, William H.; Martinez, Ashley R.; Khan, Omar I.; Liew, Clarissa J.; Dustin, Irene M.] NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA.
[Auh, Sungyoung] NINDS, Off Clin Director, NIH, Bethesda, MD 20892 USA.
[Heiss, John] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Sato, Susumu] NINDS, EEG Sect, NIH, Bethesda, MD 20892 USA.
RP Theodore, WH (reprint author), NINDS, Clin Epilepsy Sect, NIH, Bldg 10,Room 7D-43, Bethesda, MD 20892 USA.
EM theodorw@ninds.nih.gov
OI Heiss, John/0000-0002-3890-0165
FU NINDS Division of Intramural Research
FX The study was supported by the NINDS Division of Intramural Research. No
other potential conflict of interest relevant to this article was
reported.
NR 36
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U1 0
U2 2
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA
SN 0161-5505
J9 J NUCL MED
JI J. Nucl. Med.
PD SEP
PY 2012
VL 53
IS 9
BP 1375
EP 1382
DI 10.2967/jnumed.112.103093
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 004MF
UT WOS:000308685100020
PM 22782314
ER
PT J
AU Pichika, R
Taha, AY
Gao, F
Kotta, K
Cheon, Y
Chang, L
Kiesewetter, D
Rapoport, SI
Eckelman, WC
AF Pichika, Rama
Taha, Ameer Y.
Gao, Fei
Kotta, Kishore
Cheon, Yewon
Chang, Lisa
Kiesewetter, Dale
Rapoport, Stanley I.
Eckelman, William C.
TI The Synthesis and In Vivo Pharmacokinetics of Fluorinated Arachidonic
Acid: Implications for Imaging Neuroinflammation
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Article
DE positron emitting tomography (PET); fluorinated arachidonic acid;
fluoroarachidonic acid; brain; phospholipids; arachidonic acid
signaling; imaging; neuroinflammation; excitotoxicity; biomarker;
Alzheimer's disease; cancer
ID POSITRON-EMISSION-TOMOGRAPHY; THIN-LAYER CHROMATOGRAPHY; BRAIN
LIPID-METABOLISM; HIV-1 TRANSGENIC RATS; 20-FLUOROARACHIDONIC
ACID; UNANESTHETIZED RATS; FATTY-ACID; PHOSPHOLIPIDS; INFLAMMATION;
GLUCOSE
AB Arachidonic acid (AA) is found in high concentrations in brain phospholipids and is released as a second messenger during neurotransmission and much more so during neuroinflammation and excitotoxicity. Upregulated brain AA metabolism associated with neuroinflammation has been imaged in rodents using [1-C-14]AA and with PET in Alzheimer disease patients using [1-C-11]AA. Radiotracer brain AA uptake is independent of cerebral blood flow, making it an ideal tracer despite altered brain functional activity. However, the 20.4-min radioactive half-life of C-11-AA and challenges of routinely synthesizing C-11 fatty acids limit their translational utility as PET biomarkers. Methods: As a first step to develop a clinically useful F-18-fluoroarachidonic acid (F-18-FAA) with a long radioactive half-life of 109.8 min, we report here a high-yield stereoselective synthetic method of non-radioactive 20-F-19-FAA. We tested its in vivo pharmacokinetics by infusing purified nonradioactive F-19-FAA intravenously for 5 min at 2 doses in unanesthetized mice and measured its plasma and brain distribution using gas chromatography-mass spectrometry. Results: Incorporation coefficients of injected F-19-FAA into brain phospholipids (ratio of brain F-19-FAA concentration to plasma input function) were 3- to 29-fold higher for choline glycerophospholipid and phosphatidylinositol than for ethanolamine glycerophospholipid and phosphatidylserine at each of the 2 tested doses. The selectivities and values of incorporation coefficients were comparable to those reported after [1-C-14]AA (the natural arachidonate) infusion in mice. Conclusion: These results suggest that it would be worthwhile to translate our stereoselective synthetic method for F-19-FAA to synthesize positron-emitting F-18-FAA for human brain AA metabolism in neuroinflammatory disorders such as Alzheimer disease.
C1 [Pichika, Rama; Kotta, Kishore; Eckelman, William C.] Univ Calif San Diego, Dept Radiol, UCSD Ctr Mol Imaging, San Diego, CA 92121 USA.
[Taha, Ameer Y.; Gao, Fei; Cheon, Yewon; Chang, Lisa; Rapoport, Stanley I.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
[Kiesewetter, Dale] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA.
RP Eckelman, WC (reprint author), Univ Calif San Diego, Dept Radiol, UCSD Ctr Mol Imaging, 11388 Sorrento Valley Rd 100, San Diego, CA 92121 USA.
EM weckelman@ucsd.edu
RI Taha, Ameer/E-1979-2013
FU Society of Nuclear Medicine Covidien Seed Grant; Intramural Research
Program of the National Institute on Aging, National Institutes of
Health; Intramural Program of the National Institute of Biomedical
Imaging and Bioengineering, National Institutes of Health
FX We acknowledge the NCI editorial board for reviewing the paper and
providing valuable comments. Financial support for this research was
provided by the Society of Nuclear Medicine Covidien Seed Grant; by the
Intramural Research Program of the National Institute on Aging, National
Institutes of Health; and by the Intramural Program of the National
Institute of Biomedical Imaging and Bioengineering, National Institutes
of Health. No other potential conflict of interest relevant to this
article was reported.
NR 42
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U1 2
U2 14
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA
SN 0161-5505
EI 1535-5667
J9 J NUCL MED
JI J. Nucl. Med.
PD SEP
PY 2012
VL 53
IS 9
BP 1383
EP 1391
DI 10.2967/jnumed.112.105734
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 004MF
UT WOS:000308685100021
PM 22851635
ER
PT J
AU Beydoun, MA
Canas, JA
Beydoun, HA
Chen, XL
Shroff, MR
Zonderman, AB
AF Beydoun, May A.
Canas, J. Atilio
Beydoun, Hind A.
Chen, Xiaoli
Shroff, Monal R.
Zonderman, Alan B.
TI Serum Antioxidant Concentrations and Metabolic Syndrome Are Associated
among U.S. Adolescents in Recent National Surveys
SO JOURNAL OF NUTRITION
LA English
DT Article
ID NUTRITION EXAMINATION SURVEY; RETINOL-BINDING-PROTEIN; C-REACTIVE
PROTEIN; DEPENDENT DIABETES-MELLITUS; PLASMA BETA-CAROTENE; ARTERY RISK
DEVELOPMENT; ALPHA-TOCOPHEROL LEVELS; CORONARY-HEART-DISEASE; BODY-MASS
INDEX; INSULIN-RESISTANCE
AB Specific micronutrients, including retinol, retinyl esters, carotenoids beta-carotene, delta-carotene (cis+trans), p-cryptoxanthin, lutein+zeaxanthin, and total lycopene], vitamin E, and vitamin C have antiinflammatory and antioxidant effects, properties shown to reduce oxidative stress, a process that accompanies the pathogenesis of many chronic diseases. It is still largely unknown whether they are associated with the occurrence of metabolic syndrome (MetS) in the adolescent U.S. population. MetS was defined by the International Diabetes Federation (IDF) criteria. Other non-MetS outcomes relying on blood measurements were elevated HOMA-IR, C-reactive protein (CRP), and hyperuricemia. We tested associations between serum antioxidants and MetS outcomes among adolescents aged 12-19 gamma using cross-sectional data from NHANES 2001-2006 (n = 782-4285). IDF MetS prevalence was estimated at 7% among boys and 3% among girls. In adjusted models, adolescents with MetS had consistently lower carotenoid concentrations compared with their counterparts without MetS. Total carotenoids were also inversely related to HOMA-IR and CRP. Vitamin C was inversely related to uric acid level and MetS binary outcome, Retinol+retinyl esters exhibited an inverse relationship with CRP and a positive relationship with uric acid and HOMA-IR as well as MetS binary outcome. Vitamin E had no association with MetS, particularly after controlling for serum cholesterol and TG. In conclusion, among U.S. adolescents, serum carotenoid concentrations were inversely associated with MetS status, HOMA-IR, and CRP, whereas serum vitamin C was inversely related to MetS status and serum uric acid. Vitamin E had no consistent association with MetS, whereas retinol+retinyl esters had a positive relationship with HOMA-IR, uric acid, and MetS, while being inversely related to CRP. These associations need further study. J. Nutr. 142: 1693-1704,2012.
C1 [Beydoun, May A.; Zonderman, Alan B.] NIA, NIH, Baltimore, MD 21224 USA.
[Beydoun, May A.; Zonderman, Alan B.] Intramural Res Program, Baltimore, MD USA.
[Canas, J. Atilio] Pediat Endocrinol Diabet & Metab Nemours Children, Jacksonville, FL USA.
[Beydoun, Hind A.] Eastern Virginia Med Sch, Grad Program Publ Hlth, Norfolk, VA 23501 USA.
[Chen, Xiaoli] Johns Hopkins Univ, Dept Int Hlth, Bloomberg Sch Publ Hlth, Ctr Human Nutr, Baltimore, MD USA.
[Shroff, Monal R.] Michigan Publ Hlth Inst, Okemos, MI USA.
RP Beydoun, MA (reprint author), NIA, NIH, Baltimore, MD 21224 USA.
EM baydounm@mail.nih.gov
OI Zonderman, Alan B/0000-0002-6523-4778
FU National Institute on Aging, Intramural Research
FX Supported by the National Institute on Aging, Intramural Research.
NR 108
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U1 0
U2 14
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 2012
VL 142
IS 9
BP 1693
EP 1704
DI 10.3945/jn.112.160416
PG 12
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 994CF
UT WOS:000307907800012
PM 22810988
ER
PT J
AU Pullikotil, P
Chen, H
Muniyappa, R
Greenberg, CC
Yang, ST
Reiter, CEN
Lee, JW
Chung, JH
Quon, MJ
AF Pullikotil, Philomena
Chen, Hui
Muniyappa, Ranganath
Greenberg, Cynthia C.
Yang, Shutong
Reiter, Chad E. N.
Lee, Ji-Won
Chung, Jay H.
Quon, Michael J.
TI Epigallocatechin gallate induces expression of heme oxygenase-1 in
endothelial cells via p38 MAPK and Nrf-2 that suppresses proinflammatory
actions of TNF-alpha
SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY
LA English
DT Article
DE Epigallocatechin gallate (EGCG); Heme oxygenase-1; p38 kinase; Nuclear
factor-E2-related factor-2; Endothelium
ID GREEN TEA POLYPHENOL; ANTIOXIDANT RESPONSE ELEMENT; IMPROVES INSULIN
SENSITIVITY; HUMAN NEUROBLASTOMA-CELLS; MAMMARY EPITHELIAL-CELLS;
ACTIVATED PROTEIN-KINASE; TRANSCRIPTION FACTOR; NITRIC-OXIDE; VASCULAR
ENDOTHELIUM; ADHESION MOLECULES
AB Epigallocatechin gallate (EGCG), the major polyphenol in green tea, acutely stimulates production of nitric oxide (NO) from vascular endothelium to reduce hypertension and improve endothelial dysfunction in spontaneously hypertensive rats. Herein, we explored additional mechanisms whereby EGCG may mediate beneficial cardiovascular actions. When compared with vehicle-treated controls, EGCG treatment (2.5 mu M, 8 h) of human aortic endothelial cells (HAEC) caused a similar to three-fold increase in heme oxygenase-1 (HO-1) mRNA and protein with comparable increases in HO-1 activity. This was unaffected by pretreatment of cells with wortmannin, LY294002, PD98059 or L-NAME (PI 3-kinase, MEK and NO synthase inhibitors, respectively). Pretreatment of HAEC with SB203580 (p38 MAPK inhibitor) or siRNA knockdown of p38 MAPK completely blocked EGCG-stimulated induction of HO-1. EGCG treatment also inhibited tumor-necrosis-factor-alpha-stimulated expression of vascular cell adhesion molecule (VCAM)-1 and decreased adhesion of monocytes to HAEC. siRNA knockdown of HO-1, p38 MAPK or Nrf-2 blocked these inhibitory actions of EGCG. In HAEC transiently transfected with a human HO-1 promoter luciferase reporter (or an isolated Nrf-2 responsive region), luciferase activity increased in response to EGCG. This was inhibitable by SB203580 pretreatment. EGCG-stimulated expression of HO-1 and Nrf-2 was blocked by siRNA knockdown of Nrf-2 or p38 MAPK. Finally, liver from mice chronically treated with EGCG had increased HO-1 and decreased VCAM-1 expression. Thus, in vascular endothelium, EGCG requires p38 MAPK to increase expression of Nrf-2 that drives expression of HO-1, resulting in increased HO-1 activity. Increased HO-1 expression may underlie anti-inflammatory actions of EGCG in vascular endothelium that may help mediate beneficial cardiovascular actions of green tea. Published by Elsevier Inc.
C1 [Pullikotil, Philomena; Chen, Hui; Muniyappa, Ranganath; Greenberg, Cynthia C.; Reiter, Chad E. N.; Lee, Ji-Won; Quon, Michael J.] Natl Ctr Complementary & Alternat Med, Diabet Unit, Bethesda, MD 20892 USA.
[Yang, Shutong; Chung, Jay H.] NHLBI, Lab Obes & Aging Res, NIH, Bethesda, MD 20892 USA.
RP Quon, MJ (reprint author), Univ Maryland, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
EM quonm@medicine.umaryland.edu
OI Quon, Michael/0000-0002-9601-9915
FU Intramural Research Program; National Center for Complementary and
Alternative Medicine, National Institutes of Health; NHLBI; American
Diabetes Association; Office of Dietary Supplements, National Institutes
of Health
FX This work was supported in part by the Intramural Research Program,
National Center for Complementary and Alternative Medicine, National
Institutes of Health (M.J.Q) and NHLBI (J.H.C); in part by a Clinical
Research Award from the American Diabetes Association (M.J.Q); and in
part by a grant from the Office of Dietary Supplements, National
Institutes of Health (P.P.).
NR 69
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Z9 37
U1 0
U2 27
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0955-2863
J9 J NUTR BIOCHEM
JI J. Nutr. Biochem.
PD SEP
PY 2012
VL 23
IS 9
BP 1134
EP 1145
DI 10.1016/j.jnutbio.2011.06.007
PG 12
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA 994BJ
UT WOS:000307905500014
PM 22137262
ER
PT J
AU Moss, HB
Chen, CM
Yi, HY
AF Moss, Howard B.
Chen, Chiung M.
Yi, Hsiao-Ye
TI Measures of Substance Consumption Among Substance Users, DSM-IV Abusers,
and Those With DSM-IV Dependence Disorders in a Nationally
Representative Sample
SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS
LA English
DT Article
ID ALCOHOL-USE DISORDERS; GENERAL-POPULATION SAMPLE; EPIDEMIOLOGIC SURVEY;
LATENT STRUCTURE; DRINKING; RELIABILITY; FUTURE
AB Objective: Neither the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised (DSM-III-R), nor the DSM-IV uses measures of substance consumption as part of the diagnostic criteria for substance use disorders. Therefore, this report examined the extent to which frequency and/or quantity of consumption across a broad spectrum of substances are associated with DSM-IV diagnoses of specific substance use disorders and whether there are informative hierarchical levels of consumption among users, abusers, and those who are substance dependent in the U.S. general population. Method: The analyses focused on consumption data from respondents of the 2001-2002 National Epidemiologic Survey of Alcohol and Related Disorders. Multinomial logistic regression was used to predict DSM-IV diagnoses of dependence or abuse based on the continuous consumption measures. Results: Among individuals who used substances, the substances with the greatest liability for dependence were nicotine first and cocaine second. For nearly all substances investigated, users without specific substance use disorders demonstrated lower levels of quantity and frequency of consumption relative to those with DSM-IV abuse and dependence disorders. Dose-response curves for the log odds of abuse and dependence suggested unidimensionality of abuse and dependence for frequency of alcohol drinking; frequency of cannabis use; frequency of opioid use; frequency of hallucinogen use; and, to a lesser extent, frequency of amphetamine use. However, the dose-response curves for the quantity of alcohol consumed demonstrated differential patterns for abuse and dependence such that alcohol dependence has a distinctly greater "quantity of use" relationship than that found among alcohol-abusing individuals. Conclusions: These results confirm the findings of others concerning the unidimensionality of abuse and dependence diagnoses when consumption variables alone are examined and suggest that consumption measures may be useful metrics gauging severity. (J. Stud. Alcohol Drugs, 73, 820-828, 2012)
C1 [Moss, Howard B.] NIAAA, Off Director, NIH, Bethesda, MD 20892 USA.
[Chen, Chiung M.; Yi, Hsiao-Ye] CSR Inc, Alcohol Epidemiol Data Syst, Arlington, VA USA.
RP Moss, HB (reprint author), NIAAA, Off Director, NIH, Room 2007,MSC 9304,5635 Fishers Lane, Bethesda, MD 20892 USA.
EM mossh@mail.nih.gov
NR 24
TC 12
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U1 2
U2 9
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 2012
VL 73
IS 5
BP 820
EP 828
PG 9
WC Substance Abuse; Psychology
SC Substance Abuse; Psychology
GA 009PL
UT WOS:000309037600013
PM 22846246
ER
PT J
AU Rapp, SR
Legault, C
Espeland, MA
Resnick, SM
Hogan, PE
Coker, LH
Dailey, M
Shumaker, SA
AF Rapp, Stephen R.
Legault, Claudine
Espeland, Mark A.
Resnick, Susan M.
Hogan, Patricia E.
Coker, Laura H.
Dailey, Maggie
Shumaker, Sally A.
CA CAT Study Grp
TI Validation of a Cognitive Assessment Battery Administered over the
Telephone
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE cognition; assessment; telephone; validation; tests
ID MINI-MENTAL STATE; ALZHEIMERS-DISEASE; STATUS TICS; IMPAIRMENT;
DEMENTIA; INTERVIEW; VALIDITY; HEALTH; RELIABILITY; MEMORY
AB Objectives To evaluate the validity and reliability of a cognitive test battery and questionnaires administered by telephone. Design Observational study; 110 participants randomly assigned to receive two administrations of the same cognitive test battery 6 months apart in one of four combinations (Time 1 administration/Time 2 administration): telephone/telephone, telephone/face to face, face to face/telephone, face to face/face to face. Setting Academic medical center. Participants One hundred ten women aged 65 to 90 without dementia. Measurements The battery included tests of attention; verbal learning and memory; verbal fluency; executive function; working memory; global cognitive functioning; and self-reported measures of perceived memory problems, depressive symptoms, sleep disturbance, and health-related quality of life. Testretest reliability, concurrent validity, relative bias associated with telephone administration, and change scores were evaluated. Results There were no statistically significant differences in scores on any of the cognitive tests or questionnaires between participants randomly assigned to telephone or face-to-face administration at the Time 1 assessment, indicating equivalence across administration modes. There was no significant bias for tests or questionnaires administered by telephone (P's > .01), nor was there a difference in mean change scores between administration modes except for Category Fluency (P = .01) and California Verbal Learning Test long-delay free recall (P = .004). Mean testretest coefficients for the battery were not significantly different between groups, although individual testretest correlation coefficients were generally higher within modes than between modes. Conclusion Telephone administration of cognitive tests and questionnaires to older women is reliable and valid. Use of telephone batteries can substantially reduce the cost and burden of cognitive assessments and increase enrollment, retention, and data completeness, thereby improving study validity.
C1 [Rapp, Stephen R.] Wake Forest Univ, Bowman Gray Sch Med, Dept Psychiat & Behav Med, Winston Salem, NC 27157 USA.
[Rapp, Stephen R.; Legault, Claudine; Espeland, Mark A.; Hogan, Patricia E.; Coker, Laura H.; Dailey, Maggie; Shumaker, Sally A.] Wake Forest Univ, Bowman Gray Sch Med, Div Publ Hlth Sci, Winston Salem, NC 27157 USA.
[Resnick, Susan M.] NIA, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA.
RP Rapp, SR (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Psychiat & Behav Med, Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM srapp@wakehealth.edu
FU Intramural Research Program, National Institute on Aging (NIA), National
Institutes of Health; General Clinical Research Center of Wake Forest
University Baptist Medical Center [M01-RR07122]
FX The editor in chief has reviewed the conflict of interest checklist
provided by the authors and has determined that the authors have no
financial or any other kind of personal conflicts with this paper. The
Intramural Research Program, National Institute on Aging (NIA), National
Institutes of Health, and the General Clinical Research Center of Wake
Forest University Baptist Medical Center funded the CAT (M01-RR07122).
NR 37
TC 18
Z9 18
U1 2
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD SEP
PY 2012
VL 60
IS 9
BP 1616
EP 1623
DI 10.1111/j.1532-5415.2012.04111.x
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 008ER
UT WOS:000308940700003
PM 22985137
ER
PT J
AU Ferrucci, L
Schrack, JA
Simonsick, EM
Knuth, ND
AF Ferrucci, Luigi
Schrack, Jennifer A.
Simonsick, Eleanor M.
Knuth, Nicolas D.
TI Aging and the Energetic Cost of Life
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Editorial Material
ID EXPENDITURE; METABOLISM; MORTALITY
C1 [Ferrucci, Luigi; Schrack, Jennifer A.; Simonsick, Eleanor M.] NIA, Sect Clin Res Branch, NIH, Baltimore, MD 21224 USA.
[Knuth, Nicolas D.] Towson Univ, Dept Kinesiol, Towson, MD USA.
RP Ferrucci, L (reprint author), NIA, Sect Clin Res Branch, NIH, Baltimore, MD 21224 USA.
FU Intramural NIH HHS [Z99 AG999999]
NR 7
TC 7
Z9 7
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD SEP
PY 2012
VL 60
IS 9
BP 1768
EP 1769
DI 10.1111/j.1532-5415.2012.04102.x
PG 2
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 008ER
UT WOS:000308940700025
PM 22985146
ER
PT J
AU Gao, F
Kasprzak, W
Stupina, VA
Shapiro, BA
Simon, AE
AF Gao, Feng
Kasprzak, Wojciech
Stupina, Vera A.
Shapiro, Bruce A.
Simon, Anne E.
TI A Ribosome-Binding, 3 ' Translational Enhancer Has a T-Shaped Structure
and Engages in a Long-Distance RNA-RNA Interaction
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CAP-INDEPENDENT TRANSLATION; TURNIP CRINKLE VIRUS;
CURRANT-REVERSION-NEPOVIRUS; PLANT VIRAL RNAS; MESSENGER-RNA;
3'-UNTRANSLATED REGIONS; GENE-EXPRESSION; MOSAIC-VIRUS; ELEMENT;
INITIATION
AB Many plant RNA viruses contain elements in their 3' untranslated regions (3' UTRs) that enhance translation. The PTE (Panicum mosaic virus-like translational enhancer) of Pea enation mosaic virus (PEMV) binds to eukaryotic initiation factor 4E (eIF4E), but how this affects translation from the 5' end is unknown. We have discovered a three-way branched element just upstream of the PEMV PTE that engages in a long-distance kissing-loop interaction with a coding sequence hairpin that is critical for the translation of a reporter construct and the accumulation of the viral genome in vivo. Loss of the long-distance interaction was more detrimental than elimination of the adjacent PTE, indicating that the RNA-RNA interaction supports additional translation functions besides relocating the PTE to the 5' end. The branched element is predicted by molecular modeling and molecular dynamics to form a T-shaped structure (TSS) similar to the ribosome-binding TSS of Turnip crinkle virus (TCV). The PEMV element binds to plant 80S ribosomes with a K-d (dissociation constant) of 0.52 mu M and to 60S subunits with a K-d of 0.30 mu M. Unlike the TCV TSS, the PEMV element also binds 40S subunits (K-d, 0.36 mu M). Mutations in the element that suppressed translation reduced either ribosome binding or the RNA-RNA interaction, suggesting that ribosome binding is important for function. This novel, multifunctional element is designated a kl-TSS (kissing-loop T-shaped structure) to distinguish it from the TCV TSS. The kl-TSS has sequence and structural features conserved with the upper portion of most PTE-type elements, which, with the exception of the PEMV PTE, can engage in similar long-distance RNA-RNA interactions.
C1 [Shapiro, Bruce A.] NCI, Ctr Canc Res, Nanobiol Program, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA.
[Gao, Feng; Stupina, Vera A.; Simon, Anne E.] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA.
[Kasprzak, Wojciech] SAIC Frederick Inc, Basic Sci Program, Ctr Canc Res, Nanobiol Program,Frederick Natl Lab Canc Res, Frederick, MD USA.
RP Shapiro, BA (reprint author), NCI, Ctr Canc Res, Nanobiol Program, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA.
EM shapirbr@mail.nih.gov; simona@umd.edu
RI Simon, Anne/B-8713-2014; Gao, Feng/K-4403-2015
FU U.S. Public Health Service [GM 061515-05A2/G120CD, GM 061515-07S1]; NSF
[MCB 1157906]; Frederick National Laboratory for Cancer Research,
National Institutes of Health [HHSN 261200800001E]; Intramural Research
Program of the National Institutes of Health, Frederick National
Laboratory for Cancer Research, Center for Cancer Research
FX This work was supported by grants from the U.S. Public Health Service
(GM 061515-05A2/G120CD and GM 061515-07S1) and NSF (MCB 1157906) to
A.E.S. This publication has been funded in part with federal funds from
the Frederick National Laboratory for Cancer Research, National
Institutes of Health, under contract HHSN 261200800001E, to W.K. This
research was supported in part by the Intramural Research Program of the
National Institutes of Health, Frederick National Laboratory for Cancer
Research, Center for Cancer Research, to B.A.S.
NR 57
TC 18
Z9 18
U1 1
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 2012
VL 86
IS 18
BP 9828
EP 9842
DI 10.1128/JVI.00677-12
PG 15
WC Virology
SC Virology
GA 999TI
UT WOS:000308337500026
PM 22761367
ER
PT J
AU Chang, A
Hackett, BA
Winter, CC
Buchholz, UJ
Dutch, RE
AF Chang, Andres
Hackett, Brent A.
Winter, Christine C.
Buchholz, Ursula J.
Dutch, Rebecca Ellis
TI Potential Electrostatic Interactions in Multiple Regions Affect Human
Metapneumovirus F-Mediated Membrane Fusion
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID RESPIRATORY SYNCYTIAL VIRUS; LOW-PH; IN-VITRO; NONHUMAN-PRIMATES;
PARAMYXOVIRUS F; PROTEIN; HEMAGGLUTININ; REPLICATION; INFECTIONS;
RESIDUES
AB The recently identified human metapneumovirus (HMPV) is a worldwide respiratory virus affecting all age groups and causing pneumonia and bronchiolitis in severe cases. Despite its clinical significance, no specific antiviral agents have been approved for treatment of HMPV infection. Unlike the case for most paramyxoviruses, the fusion proteins (F) of a number of strains, including the clinical isolate CAN97-83, can be triggered by low pH. We recently reported that residue H435 in the HRB linker domain acts as a pH sensor for HMPV CAN97-83 F, likely through electrostatic repulsion forces between a protonated H435 and its surrounding basic residues, K295, R396, and K438, at low pH. Through site-directed mutagenesis, we demonstrated that a positive charge at position 435 is required but not sufficient for F-mediated membrane fusion. Arginine or lysine substitution at position 435 resulted in a hyperfusogenic F protein, while replacement with aspartate or glutamate abolished fusion activity. Studies with recombinant viruses carrying mutations in this region confirmed its importance. Furthermore, a second region within the F-2 domain identified as being rich in charged residues was found to modulate fusion activity of HMPV F. Loss of charge at residues E51, D54, and E56 altered local folding and overall stability of the F protein, with dramatic consequences for fusion activity. As a whole, these studies implicate charged residues and potential electrostatic interactions in function, pH sensing, and overall stability of HMPV F.
C1 [Chang, Andres; Hackett, Brent A.; Dutch, Rebecca Ellis] Univ Kentucky, Dept Mol & Cellular Biochem, Lexington, KY 40536 USA.
[Winter, Christine C.; Buchholz, Ursula J.] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA.
RP Dutch, RE (reprint author), Univ Kentucky, Dept Mol & Cellular Biochem, Lexington, KY 40536 USA.
EM rdutc2@uky.edu
FU NIH from National Center for Research Resources [R01AI051517, 2P20
RR020171]; AHA Great Rivers Affiliate predoctoral fellowship
[10PRE4230022]; Intramural Research Program of the NIH, NIAID Division
FX This work was supported by NIH grants R01AI051517 and 2P20 RR020171 from
the National Center for Research Resources to R.E.D., by AHA Great
Rivers Affiliate predoctoral fellowship 10PRE4230022 to A.C., and by
funds from the Intramural Research Program of the NIH, NIAID Division,
to U.J.B. and C.C.W.
NR 42
TC 10
Z9 12
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 2012
VL 86
IS 18
BP 9843
EP 9853
DI 10.1128/JVI.00639-12
PG 11
WC Virology
SC Virology
GA 999TI
UT WOS:000308337500027
PM 22761366
ER
PT J
AU Schountz, T
Acuna-Retamar, M
Feinstein, S
Prescott, J
Torres-Perez, F
Podell, B
Peters, S
Ye, CY
Black, WC
Hjelle, B
AF Schountz, Tony
Acuna-Retamar, Mariana
Feinstein, Shira
Prescott, Joseph
Torres-Perez, Fernando
Podell, Brendan
Peters, Staci
Ye, Chunyan
Black, William C.
Hjelle, Brian
TI Kinetics of Immune Responses in Deer Mice Experimentally Infected with
Sin Nombre Virus
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HANTAVIRUS PULMONARY SYNDROME; MOUSE PEROMYSCUS-MANICULATUS; VIRAL-RNA
PANHANDLE; CHEMOATTRACTANT PROTEIN-1 MCP-1; SYRIAN GOLDEN-HAMSTER;
T-CELLS; SEOUL-VIRUS; EXPRESSION; MODEL; DISEASE
AB Deer mice are the principal reservoir hosts of Sin Nombre virus, the etiologic agent of most hantavirus cardiopulmonary syndrome cases in North America. Infection of deer mice results in persistence without conspicuous pathology, and most, if not all, infected mice remain infected for life, with periods of viral shedding. The kinetics of viral load, histopathology, virus distribution, and immune gene expression in deer mice were examined. Viral antigen was detected as early as 5 days postinfection and peaked on day 15 in the lungs, hearts, kidneys, and livers. Viral RNA levels varied substantially but peaked on day 15 in the lungs and heart, and antinucleocapsid IgG antibodies appeared in some animals on day 10, but a strong neutralizing antibody response failed to develop during the 20-day experiment. No clinical signs of disease were observed in any of the infected deer mice. Most genes were repressed on day 2, suggesting a typical early downregulation of gene expression often observed in viral infections. Several chemokine and cytokine genes were elevated, and markers of a T cell response occurred but then declined days later. Splenic transforming growth factor beta (TGF-beta) expression was elevated early in infection, declined, and then was elevated again late in infection. Together, these data suggest that a subtle immune response that fails to clear the virus occurs in deer mice.
C1 [Schountz, Tony; Feinstein, Shira; Peters, Staci] Univ Colorado, Sch Biol Sci, Greeley, CO USA.
[Acuna-Retamar, Mariana] Univ Chile, Fac Ciencias Vet & Pecuarias, Dept Patol Anim, Santiago, Chile.
[Prescott, Joseph] NIH, Virol Lab, Rocky Mt Labs, Hamilton, MT USA.
[Torres-Perez, Fernando] Pontificia Univ Catolica Valparaiso, Inst Biol, Valparaiso, Chile.
[Podell, Brendan; Black, William C.] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA.
[Prescott, Joseph; Ye, Chunyan; Hjelle, Brian] Univ New Mexico, Sch Med, Ctr Infect Dis & Immun, Dept Pathol, Albuquerque, NM 87131 USA.
[Prescott, Joseph; Ye, Chunyan; Hjelle, Brian] Univ New Mexico, Sch Med, Ctr Infect Dis & Immun, Dept Biol, Albuquerque, NM 87131 USA.
[Prescott, Joseph; Ye, Chunyan; Hjelle, Brian] Univ New Mexico, Sch Med, Ctr Infect Dis & Immun, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA.
RP Schountz, T (reprint author), Univ Colorado, Sch Biol Sci, Greeley, CO USA.
EM tony.schountz@unco.edu
RI Podell, Brendan/D-8396-2017
OI Podell, Brendan/0000-0003-2548-8826
FU National Institutes of Health (NIH) [AI25489, AI054461, 2 U19 AI45452,
U01 AI 56618, AI45452]; betabetabeta Biological Honor Society; Fogarty
International Center Research [D43 TW007131]; University of Northern
Colorado
FX Funding was provided by National Institutes of Health (NIH) contract
AI25489 and NIH grant AI054461 (to T.S.); NIH grants 2 U19 AI45452, U01
AI 56618, and AI45452 (to B.H.); the beta beta beta Biological Honor
Society (S.F., S.P.); Fogarty International Center Research grant D43
TW007131 (M.A.-R., F.T.-P.), and the University of Northern Colorado
(T.S.).
NR 40
TC 19
Z9 19
U1 1
U2 25
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 2012
VL 86
IS 18
BP 10015
EP 10027
DI 10.1128/JVI.06875-11
PG 13
WC Virology
SC Virology
GA 999TI
UT WOS:000308337500043
PM 22787210
ER
PT J
AU Sekhar, V
McBride, AA
AF Sekhar, Vandana
McBride, Alison A.
TI Phosphorylation Regulates Binding of the Human Papillomavirus Type 8 E2
Protein to Host Chromosomes
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID PROTEASOME-MEDIATED DEGRADATION; BOVINE PAPILLOMAVIRUS; KINASE-A;
MITOTIC CHROMOSOMES; NUCLEAR ANTIGEN; COPY NUMBER; REPLICATION; BRD4;
DNA; ASSOCIATION
AB The papillomavirus E2 proteins are indispensable for the viral life cycle, and their functions are subject to tight regulation. The E2 proteins undergo posttranslational modifications that regulate their properties and roles in viral transcription, replication, and genome maintenance. During persistent infection, the E2 proteins from many papillomaviruses act as molecular bridges that tether the viral genomes to host chromosomes to retain them within the host nucleus and to partition them to daughter cells. The betapapillomavirus E2 proteins bind to pericentromeric regions of host mitotic chromosomes, including the ribosomal DNA loci. We recently reported that two residues (arginine 250 and serine 253) within the chromosome binding region of the human papillomavirus type 8 (HPV8) E2 protein are required for this binding. In this study, we show that serine 253 is phosphorylated, most likely by protein kinase A, and this modulates the interaction of the E2 protein with cellular chromatin. Furthermore, we show that this phosphorylation occurs in S phase, increases the half-life of the E2 protein, and promotes chromatin binding from S phase through mitosis.
C1 [Sekhar, Vandana; McBride, Alison A.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP McBride, AA (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
EM amcbride@nih.gov
OI McBride, Alison/0000-0001-5607-5157
FU NIAID, NIH
FX This work was funded by the Intramural Research Program of the NIAID,
NIH.
NR 44
TC 13
Z9 13
U1 0
U2 1
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 2012
VL 86
IS 18
BP 10047
EP 10058
DI 10.1128/JVI.01140-12
PG 12
WC Virology
SC Virology
GA 999TI
UT WOS:000308337500046
PM 22787207
ER
PT J
AU Caruana, DA
Alexander, GM
Dudek, SM
AF Caruana, Douglas A.
Alexander, Georgia M.
Dudek, Serena M.
TI New insights into the regulation of synaptic plasticity from an
unexpected place: Hippocampal area CA2
SO LEARNING & MEMORY
LA English
DT Review
ID LONG-TERM POTENTIATION; CALCIUM-BINDING PROTEINS; OCULAR DOMINANCE
COLUMNS; VASOPRESSIN 1B RECEPTOR; MONKEY STRIATE CORTEX; ADULT-RAT
HIPPOCAMPUS; SUPRAMAMMILLARY NUCLEUS; VISUAL-CORTEX; SUBSTANCE-P;
GUINEA-PIG
AB The search for molecules that restrict synaptic plasticity in the brain has focused primarily on sensory systems during early postnatal development, as critical periods for inducing plasticity in sensory regions are easily defined. The recent discovery that Schaffer collateral inputs to hippocampal area CA2 do not readily support canonical activity-dependent long-term potentiation (LTP) serves as a reminder that the capacity for synaptic modification is also regulated anatomically across different brain regions. Hippocampal CA2 shares features with other similarly "LTP-resistant" brain areas in that many of the genes linked to synaptic function and the associated proteins known to restrict synaptic plasticity are expressed there. Add to this a rich complement of receptors and signaling molecules permissive for induction of atypical forms of synaptic potentiation, and area CA2 becomes an ideal model system for studying specific modulators of brain plasticity. Additionally, recent evidence suggests that hippocampal CA2 is instrumental for certain forms of learning, memory, and social behavior, but the links between CA2-enriched molecules and putative CA2-dependent behaviors are only just beginning to be made. In this review, we offer a detailed look at what is currently known about the synaptic plasticity in this important, yet largely overlooked component of the hippocampus and consider how the study of CA2 may provide clues to understanding the molecular signals critical to the modulation of synaptic function in different brain regions and across different stages of development.
C1 [Caruana, Douglas A.; Alexander, Georgia M.; Dudek, Serena M.] NIEHS, Neurobiol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Dudek, SM (reprint author), NIEHS, Neurobiol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM dudek@niehs.nih.gov
OI Dudek, Serena M./0000-0003-4094-8368
FU Intramural Research Program of the National Institutes of Health,
National Institute of Environmental Health Sciences [Z01 ES 100221]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Environmental
Health Sciences, Z01 ES 100221. We thank David Armstrong, Jerrel Yakel,
and members of the Dudek lab for their input on earlier drafts of this
manuscript.
NR 100
TC 27
Z9 27
U1 1
U2 15
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1072-0502
J9 LEARN MEMORY
JI Learn. Mem.
PD SEP
PY 2012
VL 19
IS 9
BP 391
EP 400
DI 10.1101/lm.025304.111
PG 10
WC Neurosciences; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA 011MX
UT WOS:000309170200006
PM 22904370
ER
PT J
AU Bernardi, G
Wiley, EO
Mansour, H
Miller, MR
Orti, G
Haussler, D
O'Brien, SJ
Ryder, OA
Venkatesh, B
AF Bernardi, Giacomo
Wiley, Edward O.
Mansour, Hicham
Miller, Michael R.
Orti, Guillermo
Haussler, David
O'Brien, Stephen J.
Ryder, Oliver A.
Venkatesh, Byrappa
TI The fishes of Genome 10K
SO MARINE GENOMICS
LA English
DT Article
DE Genome 10K; Fish genome; Vertebrate genome
ID EVOLUTION
AB The Genome 10K project aims to sequence the genomes of 10,000 vertebrates, representing approximately one genome for each vertebrate genus. Since fishes (cartilaginous fishes, ray-finned fishes and lobe-finned fishes) represent more than 50% of extant vertebrates, it is planned to target 4,000 fish genomes. At present, nearly 60 fish genomes are being sequenced at various public funded labs, and under a Genome 10K and BGI pilot project. An additional 100 fishes have been identified for sequencing in the next phase of Genome 10K project. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Bernardi, Giacomo] Univ Calif Santa Cruz, Dept Ecol & Evolutionary Biol, Santa Cruz, CA 95064 USA.
[Wiley, Edward O.] Univ Kansas, Dept Ecol & Evolutionary Biol, Nat Hist Museum, Lawrence, KS 66045 USA.
[Wiley, Edward O.] Biodivers Res Ctr, Lawrence, KS USA.
[Mansour, Hicham] KAUST, Biosci & Bioengn Lab, Thuwal 239556900, Saudi Arabia.
[Miller, Michael R.] Univ Oregon, Inst Mol Biol, Eugene, OR 97403 USA.
[Orti, Guillermo] George Washington Univ, Dept Biol Sci, Washington, DC 20052 USA.
[Haussler, David] Univ Calif Santa Cruz, Howard Hughes Med Inst, CBSE ITI E2501, Santa Cruz, CA 95064 USA.
[O'Brien, Stephen J.] NCI, Lab Genom Divers, Frederick, MD 21701 USA.
[Ryder, Oliver A.] San Diego Zoo Inst Conservat Res, Escondido, CA USA.
[Venkatesh, Byrappa] Agcy Sci Technol & Res, Inst Mol & Cell Biol, Singapore, Singapore.
RP Bernardi, G (reprint author), Univ Calif Santa Cruz, Dept Ecol & Evolutionary Biol, Santa Cruz, CA 95064 USA.
EM bernardi@ucsc.edu; mcbbv@imcb.a-star.edu.sg
RI Bernardi, Giacomo/F-6346-2011; ASTAR, IMCB/E-2320-2012;
OI Bernardi, Giacomo/0000-0002-8249-4678; Venkatesh,
Byrappa/0000-0003-3620-0277
NR 9
TC 19
Z9 20
U1 0
U2 14
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1874-7787
J9 MAR GENOM
JI Mar. Genom.
PD SEP
PY 2012
VL 7
SI SI
BP 3
EP 6
DI 10.1016/j.margen.2012.02.002
PG 4
WC Genetics & Heredity; Marine & Freshwater Biology
SC Genetics & Heredity; Marine & Freshwater Biology
GA 003NB
UT WOS:000308617400002
PM 22897955
ER
PT J
AU Shafighi, M
Olariu, R
Brun, C
Fathi, AR
Djafarzadeh, S
Jakob, SM
Hunger, RE
Banic, A
Constantinescu, MA
AF Shafighi, Maziar
Olariu, Radu
Brun, Claudio
Fathi, Ali R.
Djafarzadeh, Siamak
Jakob, Stephan M.
Hunger, Robert E.
Banic, Andrej
Constantinescu, Mihai A.
TI The role of androgens on hypoxia-inducible factor (HIF)-1a-induced
angiogenesis and on the survival of ischemically challenged skin flaps
in a rat model
SO MICROSURGERY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; PROSTATE-CANCER; HEART-DISEASE; IN-VITRO;
TESTOSTERONE; NECROSIS; CELLS; HYDROXYLASES; REPERFUSION; HIF-1-ALPHA
AB Background: Effects of androgens on angiogenesis are controversial. Hypoxia-inducible factor (HIF)-1a promotes expression of vascular endothelial growth factor (VEGF) that stimulates angiogenesis. Purpose: This study investigates whether androgens stabilize HIF-1a in endothelial cells, and androgen depletion decreases VEGF concentrations and skin flap survival. Materials and Methods: Male human umbilical vein endothelial cells (HUVECs) were exposed to dihydrotestosterone (DHT) and HIF-1a expression was measured. In male Wistar rats, standardized proximally based random pattern dorsal skin flaps (3 x 9 cm) were raised 4 weeks after orchiectomy and sham operation, respectively (n = 10, each). Flap VEGF concentrations (immunohistochemistry), perfusion (Laser Doppler), and viability (digital planimetry) were measured. Results: DHT induced HIF-1a expression in HUVECs. Androgen depletion induced decreased VEGF expression (P = 0.003), flap perfusion (P < 0.05), and survival (44.4% +/- 5.2%) compared to controls (35.5% +/- 4.5%; P = 0.003). Conclusion: In vitro, androgens may stimulate HIF-1a under normoxic conditions. In rats, androgen depletion decrease VEGF expression and flap survival. (c) 2012 Wiley Periodicals, Inc. Microsurgery 2012.
C1 [Shafighi, Maziar; Olariu, Radu; Brun, Claudio; Banic, Andrej; Constantinescu, Mihai A.] Univ Bern, Univ Hosp, Inselspital, Dept Plast Reconstruct & Hand Surg, CH-3012 Bern, Switzerland.
[Fathi, Ali R.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD USA.
[Djafarzadeh, Siamak; Jakob, Stephan M.] Univ Bern, Univ Hosp, Inselspital, Dept Intens Care Med, CH-3012 Bern, Switzerland.
[Hunger, Robert E.] Univ Bern, Univ Hosp, Inselspital, Dept Dermatol, CH-3012 Bern, Switzerland.
RP Brun, C (reprint author), Univ Hosp Bern, Inselspital, Univ Clin Plast & Hand Surg, CH-3010 Bern, Switzerland.
EM c.brun@gmx.ch
NR 41
TC 4
Z9 4
U1 7
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0738-1085
J9 MICROSURG
JI Microsurgery
PD SEP
PY 2012
VL 32
IS 6
BP 475
EP 481
DI 10.1002/micr.21996
PG 7
WC Surgery
SC Surgery
GA 000NW
UT WOS:000308394100009
PM 22707412
ER
PT J
AU Hwang, SJ
Seol, HJ
Park, YM
Kim, KH
Gorospe, M
Nam, DH
Kim, HH
AF Hwang, Su Jin
Seol, Ho Jun
Park, Young Mi
Kim, Kang Ho
Gorospe, Myriam
Nam, Do-Hyun
Kim, Hyeon Ho
TI MicroRNA-146a suppresses metastatic activity in brain metastasis
SO MOLECULES AND CELLS
LA English
DT Article
DE beta-catenin; brain metastasis; HnRNPC; MicroRNA-146a
ID NF-KAPPA-B; BREAST-CANCER; BETA-CATENIN; MALIGNANT-MELANOMA;
MESSENGER-RNA; CELLS; EXPRESSION; MODEL; PROLIFERATION; DISSEMINATION
AB Primary lung tumors, breast tumors, and melanoma metastasize mainly in the brain where therapy is limited to surgery and radiation. To investigate the molecular basis of brain metastases, we isolated brain-trophic metastatic MDA-MB-435-LvBr2 (LvBr2) cells via left ventricle (LV) injection of MDA-MB-435 cells into immunodeficiency (NOD/SCID) mice. Whereas parent MDA-MB-435 cells displayed an elongated morphology, LvBr2 cells were round and displayed an aggregated distribution. LvBr2 cells expressed lower beta-catenin levels and higher heterogeneous nuclear ribonucleoprotein C1/C2 (hnRNPC) levels than parental cells. Since microRNAs are known to play an important role in cancer progression including metastasis, we screened microRNAs expressed specifically in brain metastases. MicroRNA-146a was almost undetectable in LvBr2 cells and highly expressed in the parental cells. Overexpression of miR-146a increased beta-catenin expression and suppressed the migratory and invasive activity of LvBr2 cells. The miR-146a-elicited decrease in hnRNPC in turn lowered the expression of MMP-1, uPA, and uPAR and inhibited the migratory and invasive activity of LvBr2 cells. Taken together, our findings indicate that miR-146a is virtually absent from brain metastases and can suppress their metastatic potential including their migratory and invasive activities associated with upregulation of beta-catenin and downregulation of hnRNPC.
C1 [Seol, Ho Jun; Kim, Kang Ho; Nam, Do-Hyun] Sungkyunkwan Univ, Sch Med, Canc Stem Cell Res Ctr, Dept Neurosurg, Seoul 135710, South Korea.
[Hwang, Su Jin; Park, Young Mi; Kim, Hyeon Ho] Sungkyunkwan Univ, Samsung Adv Inst Hlth Sci & Technol, Dept Hlth Sci & Technol, Seoul 135710, South Korea.
[Gorospe, Myriam] NIA, Lab Mol Biol & Immunol, IRP, NIH, Baltimore, MD 21224 USA.
[Kim, Hyeon Ho] Samsung Med Ctr, Samsung Biomed Res Inst, Seoul 135710, South Korea.
RP Nam, DH (reprint author), Sungkyunkwan Univ, Sch Med, Canc Stem Cell Res Ctr, Dept Neurosurg, Seoul 135710, South Korea.
EM nsnam@skku.edu; hyeonhkim@skku.edu
FU National Research Foundation of Korea by the Ministry of Education,
Science, and Technology [2011-009329]; Ministry of Health & Welfare
Affairs, Republic of Korea [A092255]; NIA-IRP, NIH
FX We thank Prof. Sunjoo Jeong (Dankook University, Korea) for a reporter
vector expressing GFP mRNA carrying the beta-catenin 3'UTR. This study
was supported by a grant from the Basic Science Research Program,
National Research Foundation of Korea by the Ministry of Education,
Science, and Technology (2011-009329 to H. H. Kim) and the Korea Health
Care technology R&D project, Ministry of Health & Welfare Affairs,
Republic of Korea (A092255). Myriam Gorospe was supported by the
NIA-IRP, NIH.
NR 22
TC 17
Z9 18
U1 2
U2 11
PU KOREAN SOC MOLECULAR & CELLULAR BIOLOGY
PI SEOUL
PA 635-4, YUCKSAM-DONG, GANGNAM-GU, SEOUL 135-703, SOUTH KOREA
SN 1016-8478
J9 MOL CELLS
JI Mol. Cells
PD SEP
PY 2012
VL 34
IS 3
BP 329
EP 334
DI 10.1007/s10059-012-0171-6
PG 6
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 012JO
UT WOS:000309232600013
PM 22949171
ER
PT J
AU Georgiadis, P
Kovacs, K
Kaila, S
Makedonopoulou, P
Anna, L
Poirier, MC
Knudsen, LE
Schoket, B
Kyrtopoulos, SA
AF Georgiadis, Panagiotis
Kovacs, Katalin
Kaila, Stella
Makedonopoulou, Paraskevi
Anna, Livia
Poirier, Miriam C.
Knudsen, Lisbeth E.
Schoket, Bernadette
Kyrtopoulos, Soterios A.
TI Development and validation of a direct sandwich chemiluminescence
immunoassay for measuring DNA adducts of benzo[a]pyrene and other
polycyclic aromatic hydrocarbons
SO MUTAGENESIS
LA English
DT Article
ID WHITE BLOOD-CELLS; LUNG-CANCER PATIENTS; HUMAN-PLACENTA; BREAST-CANCER;
HUMAN TISSUES; AMBIENT AIR; EXPOSURE; DAMAGE; QUANTITATION; LYMPHOCYTES
AB We have developed and validated a sandwich chemiluminescence immunoassay (SCIA) which measures polycyclic aromatic hydrocarbon (PAH)-DNA adducts combining high throughput and adequate sensitivity, appropriate for evaluation of adduct levels in human population studies. Fragmented DNA is incubated with rabbit antiserum elicited against DNA modified with r7,t8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) and subsequently trapped by goat anti-rabbit IgG bound to a solid surface. Anti-single-stranded (ss) DNA antibodies binds in a quantity proportional to the adduct levels and is detected by chemiluminescence. The BPDE DNA SCIA has a limit of detection of 3 adducts per 10(9) nucleotides with 5 mu g DNA per well. We have validated the BPDE DNA SCIA using DNA modified in vitro, DNA from benzo[a]pyrene (BP)-exposed cultured cells and mice. The levels of adduct measured by SCIA were lower (30-60%) than levels of bulky DNA adducts measured in the same samples by P-32-postlabelling. The BPDE DNA SCIA also detected adducts produced in vivo by PAHs other than BP. When blood DNA samples from maternal/infant pairs were assayed by BPDE DNA SCIA, the adduct levels obtained were significantly correlated. However, there was no correlation between P-32-postlabelling and SCIA values for the same samples. The SCIA can be extended to any DNA adduct and is expected to provide, when fully automated, a valuable high-throughput approach in large-scale population studies.
C1 [Georgiadis, Panagiotis; Kaila, Stella; Makedonopoulou, Paraskevi; Kyrtopoulos, Soterios A.] Natl Hellen Res Fdn, Inst Biol Res & Biotechnol, Athens 11635, Greece.
[Kovacs, Katalin; Anna, Livia; Schoket, Bernadette] Natl Inst Environm Hlth, H-1097 Budapest, Hungary.
[Poirier, Miriam C.] NCI, Carcinogen DNA Interact Sect, Lab Canc Biol & Genet, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Knudsen, Lisbeth E.] Univ Copenhagen, Dept Publ Hlth, DK-1014 Copenhagen, Denmark.
RP Georgiadis, P (reprint author), Natl Hellen Res Fdn, Inst Biol Res & Biotechnol, 48 Vassileos Constantinou Ave, Athens 11635, Greece.
EM panosg@eie.gr
OI Knudsen, Lisbeth E./0000-0002-9576-1202
FU European Union [FOOD-CT-2005-513943, FOOD-CT-2005-016320]; intramural
program of the Center for Cancer Research, National Cancer Institute,
National Institutes of Health, Bethesda, MD, USA
FX This work was supported by contracts from the European Union (to S.A.K):
Network of Excellence ECNIS-'Environmental cancer risk, nutrition and
individual susceptibility' and Integrated Project NewGeneris-'Newborns
and genotoxic exposure risks' (contract numbers FOOD-CT-2005-513943,
FOOD-CT-2005-016320). The work was also supported in part by the
intramural program of the Center for Cancer Research, National Cancer
Institute, National Institutes of Health, Bethesda, MD, USA (to M.C.P.).
NR 45
TC 3
Z9 4
U1 1
U2 21
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0267-8357
EI 1464-3804
J9 MUTAGENESIS
JI Mutagenesis
PD SEP
PY 2012
VL 27
IS 5
BP 589
EP 597
DI 10.1093/mutage/ges024
PG 9
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA 003RO
UT WOS:000308629200009
PM 22610669
ER
PT J
AU Kim, JS
Oh, YS
Lee, KS
Kim, YI
Yang, DW
Goldstein, DS
AF Kim, Joong-Seok
Oh, Yoon-Sang
Lee, Kwang-Soo
Kim, Yeong-In
Yang, Dong-Won
Goldstein, David S.
TI Association of cognitive dysfunction with neurocirculatory abnormalities
in early Parkinson disease
SO NEUROLOGY
LA English
DT Article
ID WHITE-MATTER HYPERINTENSITIES; ORTHOSTATIC HYPOTENSION; BLOOD-PRESSURE;
CHOLINERGIC PATHWAYS; SUPINE HYPERTENSION; BRAIN ATROPHY; LEWY BODY;
DEMENTIA; IMPAIRMENT; RISK
AB Objective: Cognitive impairment and neurocirculatory abnormalities such as orthostatic hypotension (OH), supine hypertension (SH), and failure to decrease blood pressure at night (nondipping) occur relatively commonly in Parkinson disease (PD); however, whether cognitive dysfunction in early PD is related to neurocirculatory abnormalities has not been established. Cognitive dysfunction in PD is associated with white matter hyperintensities on MRI. We report results of an analysis of neuropsychological and hemodynamic parameters in patients with early PD.
Methods: Among 87 patients, 25 had normal cognition, 48 had mild cognitive impairment, and 14 had dementia, based on comprehensive neuropsychological tests. Orthostatic vital signs and ambulatory 24-hour blood pressure monitoring were recorded, and brain magnetic resonance scans were obtained for all patients.
Results: Cognitive impairment was associated with OH, SH, and white matter hyperintensities but not with nondipping. Dementia and white matter hyperintensities were common in SH. Of 13 patients with OH + SH, every one had mild cognitive impairment or dementia.
Conclusions: Cognitive dysfunction is related to neurocirculatory abnormalities, especially OH + SH, in early PD, raising the possibility that early detection and effective treatment of those abnormalities might slow the rate of cognitive decline. Neurology (R) 2012;79:1323-1331
C1 [Kim, Joong-Seok; Oh, Yoon-Sang; Lee, Kwang-Soo; Kim, Yeong-In; Yang, Dong-Won] Catholic Univ Korea, Coll Med, Dept Neurol, Seoul, South Korea.
[Goldstein, David S.] NINDS, Clin Neurocardiol Sect, Clin Neurosci Program, Div Intramural Res,NIH, Bethesda, MD 20892 USA.
RP Kim, JS (reprint author), Catholic Univ Korea, Coll Med, Dept Neurol, Seoul, South Korea.
EM neuronet@catholic.ac.kr; goldsteind@ninds.nih.gov
FU Catholic Medical Center Research Foundation; Division of Intramural
Research of the National Institute of Neurological Disorders and Stroke
FX Supported by the Catholic Medical Center Research Foundation. Dr.
Goldstein is supported by the Division of Intramural Research of the
National Institute of Neurological Disorders and Stroke.
NR 40
TC 43
Z9 45
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD SEP
PY 2012
VL 79
IS 13
BP 1323
EP 1331
DI 10.1212/WNL.0b013e31826c1acd
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA 012TO
UT WOS:000309259700013
PM 22972639
ER
PT J
AU Junier, I
Dale, RK
Hou, CH
Kepes, F
Dean, A
AF Junier, Ivan
Dale, Ryan K.
Hou, Chunhui
Kepes, Francois
Dean, Ann
TI CTCF-mediated transcriptional regulation through cell type-specific
chromosome organization in the beta-globin locus
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID CONTROL REGION; ERYTHROID-DIFFERENTIATION; CONFORMATION CAPTURE;
GENE-EXPRESSION; CHROMATIN CONFORMATION; GENOME; REVEALS; ARCHITECTURE;
INSULATORS; PRINCIPLES
AB The principles underlying the architectural landscape of chromatin beyond the nucleosome level in living cells remains largely unknown despite its potential to play a role in mammalian gene regulation. We investigated the three-dimensional folding of a 1 Mbp region of human chromosome 11 containing the beta-globin genes by integrating looping interactions of the CCCTC-binding insulator protein CTCF determined comprehensively by chromosome conformation capture (3C) into a polymer model of chromatin. We find that CTCF-mediated cell type-specific interactions in erythroid cells are organized to favor contacts known to occur in vivo between the beta-globin locus control region (LCR) and genes. In these cells, the modeled beta-globin domain folds into a globule with the LCR and the active globin genes on the periphery. In contrast, in non-erythroid cells, the globule is less compact with few but dominant CTCF interactions driving the genes away from the LCR. This leads to a decrease in contact frequencies that can exceed 1000-fold depending on the stiffness of the chromatin and the exact position of the genes. Our findings show that an ensemble of CTCF contacts functionally affects spatial distances between control elements and target genes contributing to chromosomal organization required for transcription.
C1 [Junier, Ivan; Kepes, Francois] Univ Evry, Epigenom Project, F-91030 Evry, France.
[Junier, Ivan; Kepes, Francois] Univ Evry, CNRS, Genopole, Inst Syst & Synthet Biol, F-91030 Evry, France.
[Junier, Ivan] Inst Complex Syst, Paris, France.
[Junier, Ivan] Ctr Genom Regulat, Barcelona 08003, Spain.
[Dale, Ryan K.; Hou, Chunhui; Dean, Ann] NIDDKD, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA.
RP Junier, I (reprint author), Univ Evry, Epigenom Project, 5 Rue Henri Desbrueres, F-91030 Evry, France.
EM i.junier@gmail.com; francois.kepes@epigenomique.genopole.fr;
anndean@helix.nih.gov
OI Dale, Ryan/0000-0003-2664-3744
FU Intramural Program of the National Institute of Diabetes and Digestive
and Kidney Diseases, National Institutes of Health [KIA 15508];
Novartis; Region Ile-de-France; ISC-PIF; Sixth European Research
Framework [034952]; PRES UniverSud Paris; CNRS; Genopole; National
Institute of Diabetes, and Digestive and Kidney Diseases, National
Institutes of Health [KIA 15508]
FX Intramural Program of the National Institute of Diabetes and Digestive
and Kidney Diseases, National Institutes of Health [KIA 15508 to A.D.].
I.J. is supported by a Novartis grant (CRG) and thanks Region
Ile-de-France and ISC-PIF for financial and logistic support. This study
was also supported by the Sixth European Research Framework (project
number 034952, GENNETEC project), PRES UniverSud Paris, CNRS and
Genopole (to F.K.). Funding for open access charge: Intramural Program,
National Institute of Diabetes, and Digestive and Kidney Diseases,
National Institutes of Health [KIA 15508 to AD].
NR 51
TC 18
Z9 18
U1 0
U2 12
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 2012
VL 40
IS 16
BP 7718
EP 7727
DI 10.1093/nar/gks536
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 008LZ
UT WOS:000308959800019
PM 22705794
ER
PT J
AU Al-Haj, L
Blackshear, PJ
Khabar, KSA
AF Al-Haj, Latifa
Blackshear, Perry J.
Khabar, Khalid S. A.
TI Regulation of p21/CIP1/WAF-1 mediated cell-cycle arrest by RNase L and
tristetraprolin, and involvement of AU-rich elements
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID DEPENDENT KINASE INHIBITORS; ACTIVATED PROTEIN-KINASE; PROSTATE-CANCER
CELLS; MESSENGER-RNA; INTERFERON-ALPHA; BINDING PROTEIN; RIBONUCLEASE-L;
2',5'-OLIGOADENYLATE SYNTHETASE; 3'-UNTRANSLATED REGION; 2-5A SYSTEM
AB The p21(Cip1/WAF1) plays an important role in cell-cycle arrest. Here, we find that RNase L regulates p21-mediated G(1) growth arrest in AU-rich elements-dependent manner. We found a significant loss of p21 mRNA expression in RNASEL(-/-) MEFs and that the overexpression of RNase L in HeLa cells induces p21 mRNA expression. The p21 mRNA half-life significantly changes as a result of RNase L modulation, indicating a post-transcriptional effect. Indeed, we found that RNase L promotes tristetraprolin (TTP/ZFP36) mRNA decay. This activity was not seen with dimerization- and nuclease-deficient RNase L mutants. Deficiency in TTP led to increases in p21 mRNA and protein. With induced ablation of RNase L, TTP mRNA and protein expressions were higher, while p21 expression became reduced. We further establish that TTP, but not C124R TTP mutant, binds to, and accelerates the decay of p21 mRNA. The p21 mRNA half-life was prolonged in TTP-/- MEFs. The TTP regulation of p21 mRNA decay required functional AU-rich elements. Thus, we demonstrate a novel mechanism of regulating G(1) growth arrest by an RNase L-TTP-p21 axis.
C1 [Al-Haj, Latifa; Khabar, Khalid S. A.] King Faisal Specialist Hosp & Res Ctr, Program BioMol Res, Riyadh 11211, Saudi Arabia.
[Blackshear, Perry J.] NIH, Res Triangle Pk, NC 27709 USA.
RP Khabar, KSA (reprint author), King Faisal Specialist Hosp & Res Ctr, Program BioMol Res, Riyadh 11211, Saudi Arabia.
EM khabar@kfshrc.edu.sa
RI Khabar, Khalid/A-4772-2011
OI Khabar, Khalid/0000-0003-1003-9788
FU King Faisal Specialist Hospital and Research Centre (KFSH&RC) under the
RAC proposal [2110 014]; KFSHRC
FX The King Faisal Specialist Hospital and Research Centre (KFSH&RC) under
the RAC proposal [# 2110 014]. Funding for open access charge: KFSH&RC.
NR 57
TC 20
Z9 20
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 2012
VL 40
IS 16
BP 7739
EP 7752
DI 10.1093/nar/gks545
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 008LZ
UT WOS:000308959800021
PM 22718976
ER
PT J
AU Shrimali, S
Srivastava, S
Varma, G
Grinberg, A
Pfeifer, K
Srivastava, M
AF Shrimali, Sweety
Srivastava, Surabhi
Varma, Garima
Grinberg, Alex
Pfeifer, Karl
Srivastava, Madhulika
TI An ectopic CTCF-dependent transcriptional insulator influences the
choice of V beta gene segments for VDJ recombination at TCR beta locus
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID EMBRYONIC STEM-CELLS; HEAVY-CHAIN GENE; PRO-B CELLS; V(D)J
RECOMBINATION; H19/IGF2 LOCUS; IGH LOCUS; THYMOCYTE DEVELOPMENT;
IMPRINTED EXPRESSION; ENHANCER-BLOCKING; HUMAN GENOME
AB Insulators regulate transcription as they modulate the interactions between enhancers and promoters by organizing the chromatin into distinct domains. To gain better understanding of the nature of chromatin domains defined by insulators, we analyzed the ability of an insulator to interfere in VDJ recombination, a process that is critically dependent on long-range interactions between diverse types of cis-acting DNA elements. A well-established CTCF-dependent transcriptional insulator, H19 imprint control region (H19-ICR), was inserted in the mouse TCR beta locus by genetic manipulation. Analysis of the mutant mice demonstrated that the insulator retains its CTCF and position-dependent enhancer-blocking potential in this heterologous context in vivo. Remarkably, the inserted H19-ICR appears to have the ability to modulate cis-DNA interactions between recombination signal sequence elements of the TCR beta locus leading to a dramatically altered usage of V beta segments for V beta-to-D beta J beta recombination in the mutant mice. This reveals a novel ability of CTCF to govern long range cis-DNA interactions other than enhancer-promoter interactions and suggests that CTCF-dependent insulators may play a diverse and complex role in genome organization beyond transcriptional control. Our functional analysis of mutated TCR beta locus supports the emerging role of CTCF in governing VDJ recombination.
C1 [Shrimali, Sweety; Srivastava, Surabhi; Varma, Garima; Srivastava, Madhulika] Natl Inst Immunol, New Delhi 110067, India.
[Grinberg, Alex; Pfeifer, Karl] NICHD, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
RP Srivastava, M (reprint author), Natl Inst Immunol, Aruna Asaf Ali Rd, New Delhi 110067, India.
EM madhus@nii.res.in
FU Department of Biotechnology, India [BT/PR3815/BRB/10/318/2003,
BT/PR9088/BRB/10/538/2007]; Council of Scientific and Industrial
Research, India; National Institute of Immunology; NICHD Division of
Intramural Research; National Intitute of Immunology, New Delhi
FX Department of Biotechnology, India (research grants
BT/PR3815/BRB/10/318/2003 and BT/PR9088/BRB/10/538/2007 to M. S.);
Council of Scientific and Industrial Research, India (Senior Research
Fellowship to Sw.S.). National Institute of Immunology (support to Su.S.
and M. S.); NICHD Division of Intramural Research (support to A. G. and
K. P.). Funding for open access charge: Core Funds of National Intitute
of Immunology, New Delhi.
NR 48
TC 7
Z9 7
U1 1
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 2012
VL 40
IS 16
BP 7753
EP 7765
DI 10.1093/nar/gks556
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 008LZ
UT WOS:000308959800022
PM 22718969
ER
PT J
AU Ayres, EJ
Hoggle, LB
AF Ayres, Elaine J.
Hoggle, Lindsey B.
TI Advancing practice: Using nutrition information and technology to
improve healthuthe nutrition informatics global challenge
SO NUTRITION & DIETETICS
LA English
DT Review
DE electronic health record; health information; informatics; standard;
terminology
ID CARE PROCESS; RECORDS
AB Aims: The unique combination of technology, information and nutrition has been utilised in health care for decades. As technology and effective use of health data evolve, the field of nutrition informatics is positioned to advance best practices of nutrition care delivered by registered dietitians and dietetic technicians registered. The present paper reviews the opportunities. Methods: A narrative review was constructed with reference to the literature. Results: Evolution of the use of digital health care in the USA is on an aggressive timeline because of regulations, which provide financial incentives to eligible professionals and hospitals who can prove meaningful use of certified health-care technology. While adoption and use of electronic health records has occurred at the international level for decades, only recently have American adoption rates increased. Health-care providers are adjusting to rapid cultural changes, which support the interoperability of health data. The dietetics profession must move in tandem with this transition to digital care. This requires implementation and development of nutrition standards, vocabularies and quality measures, which support exchange of pertinent nutrition data critical to patient care and wellbeing. All dietetic professionals need to appreciate the paradigm shift in health care. Conclusions: Dietitians who are involved with informatics will help with this transition through their work with systems implementations, understanding competencies necessary for successful integration of digital nutrition and using electronic nutrition data for research.
C1 [Ayres, Elaine J.] NIH, Lab Informat Dev, Ctr Clin, Bethesda, MD 20892 USA.
[Hoggle, Lindsey B.] Acad Nutr & Dietet, Washington, DC USA.
RP Ayres, EJ (reprint author), NIH, Lab Informat Dev, Ctr Clin, 10 Ctr Dr,MSC 1504, Bethesda, MD 20892 USA.
EM eayres@cc.nih.gov
NR 14
TC 3
Z9 3
U1 3
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1446-6368
EI 1747-0080
J9 NUTR DIET
JI Nutr. Diet.
PD SEP
PY 2012
VL 69
IS 3
BP 195
EP 197
DI 10.1111/j.1747-0080.2012.01616.x
PG 3
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 007KG
UT WOS:000308886600005
ER
PT J
AU Goeckeler-Fried, J
Chiang, A
Chung, W
Havasi, V
Weissman, AJ
Lewis, T
Brodsky, JL
AF Goeckeler-Fried, J.
Chiang, A.
Chung, W.
Havasi, V
Weissman, A. J.
Lewis, T.
Brodsky, J. L.
TI SYNERGISTIC CORRECTION OF Delta F508-CFTR WHEN AN INHIBITOR OF PROTEIN
UBIQUITINATION IS COMBINED WITH A SMALL MOLECULE CORRECTOR
SO PEDIATRIC PULMONOLOGY
LA English
DT Meeting Abstract
C1 [Goeckeler-Fried, J.; Chiang, A.; Brodsky, J. L.] Univ Pittsburgh, Pittsburgh, PA USA.
[Chung, W.; Havasi, V] Univ Alabama Birmingham, Birmingham, AL USA.
[Weissman, A. J.] NCI, Ctr Canc Res, Frederick, MD 21701 USA.
[Lewis, T.] Broad Inst Harvard & MIT, Cambridge, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 8755-6863
J9 PEDIATR PULM
JI Pediatr. Pulmonol.
PD SEP
PY 2012
VL 47
SU 35
SI SI
BP 233
EP 234
PG 2
WC Pediatrics; Respiratory System
SC Pediatrics; Respiratory System
GA 007IM
UT WOS:000308882000120
ER
PT J
AU Mishra, PJ
AF Mishra, Prasun J.
TI The miRNA-drug resistance connection: a new era of personalized medicine
using noncoding RNA begins
SO PHARMACOGENOMICS
LA English
DT Editorial Material
DE diagnosis; disease; drug resistance; epidemiology; genetic variation;
genomic medicine; individualized medicine; microRNA; miRNA; miRSNP;
mutations; ncRNA; noncoding RNA; personalized medicine;
pharmacogenomics; polymorphisms; prognosis
ID HUMAN CANCER-CELLS; BREAST-CANCER; DIHYDROFOLATE-REDUCTASE; MICRORNA
POLYMORPHISMS; TAMOXIFEN RESISTANCE; OVARIAN-CANCER; LUNG-CANCER;
EXPRESSION; PHARMACOGENOMICS; THERAPY
C1 NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Mishra, PJ (reprint author), NCI, Ctr Canc Res, NIH, 37 Convent Dr, Bethesda, MD 20892 USA.
EM mishrapj@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 37
TC 13
Z9 14
U1 0
U2 11
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1462-2416
EI 1744-8042
J9 PHARMACOGENOMICS
JI Pharmacogenomics
PD SEP
PY 2012
VL 13
IS 12
BP 1321
EP 1324
DI 10.2217/PGS.12.121
PG 4
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 005UR
UT WOS:000308776100002
PM 22966880
ER
PT J
AU Karlsson, C
Zook, M
Ciccocioppo, R
Gehlert, DR
Thorsell, A
Heilig, M
Cippitelli, A
AF Karlsson, Camilla
Zook, Michelle
Ciccocioppo, Roberto
Gehlert, Donald R.
Thorsell, Annika
Heilig, Markus
Cippitelli, Andrea
TI Melanin-concentrating hormone receptor 1 (MCH1-R) antagonism: Reduced
appetite for calories and suppression of addictive-like behaviors
SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
LA English
DT Article
DE Sucrose; Saccharin; Reinstatement; Intermittent; Binging; MCH1-R
ID EXCESSIVE SUGAR INTAKE; FEEDING-BEHAVIOR; DRUG-ADDICTION; PALATABLE
FOOD; MESSENGER-RNA; RAT-BRAIN; DOPAMINE; ALCOHOL; SEEKING; SYSTEM
AB Rationale: The hypothalamic neuropeptide melanin-concentrating hormone and its MCH1 receptor have been implicated in regulation of feeding and energy homeostasis, as well as modulation of reward-related behaviors. Here, we examined whether the MCH system plays a role both in caloric and motivational aspects of sugar intake.
Materials and methods: The non-peptide MCH1-R antagonist GW803430 (3, 10, 30 mg/kg, i.p.) was firsrtested on self-administration under a fixed ratio schedule of reinforcement of both a caloric (10% w/v sucrose) and a non-caloric (0.06% w/v saccharin) sweet solution. GW803430 was then tested for its ability to alter motivational properties and seeking of sucrose. Lastly, the drug was tested to concurrently examine its effects on the escalated consumption of both sugar and food in animals following intermittent sugar access.
Results: The MCH1-R antagonist reduced sucrose- but not saccharin-reinforced lever pressing, likely reflecting a decreased appetite for calories in GW803430-treated rats. GW803430 reduced sucrose self-administration under a progressive ratio schedule, and suppressed cue-induced reinstatement of sucrose seeking, suggesting effects on rewarding properties of sucrose. GW803430 attenuated food intake in rats on intermittent access to sucrose at all doses examined (3, 10, 30 mg/kg), while reduction of sugar intake was weaker in magnitude.
Conclusion: Together, these observations support an involvement of the MCH system in regulation of energy balance as well as mediation of sucrose reward. MCH may be an important regulator of sugar intake by acting on both caloric and rewarding components. Published by Elsevier Inc.
C1 [Karlsson, Camilla; Zook, Michelle; Thorsell, Annika; Heilig, Markus; Cippitelli, Andrea] NIAAA, LCTS, NIH, Bethesda, MD 20892 USA.
[Ciccocioppo, Roberto] Univ Camerino, Sch Pharm, Pharmacol Unit, I-62032 Camerino, Italy.
[Gehlert, Donald R.] Lilly Res Labs, Neurosci & Endocrine Discovery Res, Indianapolis, IN USA.
RP Cippitelli, A (reprint author), NIAAA, LCTS, NIH, 10 Ctr Dr,1-5330, Bethesda, MD 20892 USA.
EM cippitellia@mail.nih.gov
OI Thorsell, Annika/0000-0003-3535-3845
NR 44
TC 14
Z9 14
U1 1
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0091-3057
J9 PHARMACOL BIOCHEM BE
JI Pharmacol. Biochem. Behav.
PD SEP
PY 2012
VL 102
IS 3
BP 400
EP 406
DI 10.1016/j.pbb.2012.06.010
PG 7
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA 987RJ
UT WOS:000307434500002
PM 22705492
ER
PT J
AU Liu, XY
Fang, ZZ
Dong, PP
Shi, XH
Teng, YJ
Sun, XY
AF Liu, Xiao-You
Fang, Zhong-Ze
Dong, Pei-Pei
Shi, Xiang-Hua
Teng, Yan-Jie
Sun, Xu-Yong
TI Tacrolimus strongly inhibits multiple human UDP-glucuronosyltransferase
(UGT) isoforms
SO PHARMAZIE
LA English
DT Article
ID DRUG-DRUG INTERACTIONS; LIVER CYTOCHROME-P450 ENZYMES;
HUMAN-IMMUNODEFICIENCY-VIRUS; GLUCURONIDATION; PHARMACOKINETICS;
TRANSPLANTATION; METABOLISM; ZIDOVUDINE; MICROSOMES
AB The objective of the present study is to clearly evaluate the inhibitory effects of tacrolimus (tacro) on important UGT isoforms in human liver, including determination of inhibition kinetic type and calculation of inhibition kinetic parameters. An in vitro incubation system was used to investigate the inhibitory effect of tacro on UGT isoforms. The recombinant UGT isoforms were used as enzyme source, and a nonspecific substrate 4-methylumbelliferone (4-MU) was utilized as substrate. Among the tested UGT isoforms, UGT1A1, UGT1A3, UGT2B7 and UGT2B15 were strongly inhibited by tacro in a concentration-dependent manner. Dixon and Lineweaver-Burk plots showed that the inhibition of UGT1A1, UGT1A3, and UGT2B7 was all best fit to competitive inhibition type, and the inhibition of UGT2B15 was best fit to noncompetitive type. The inhibition kinetic parameters (K-i) were determined to be 4.7, 1.3, 1.9, and 4.3 mu M for UGT1A1, UGT1A3, UGT2B7, and UGT2B15, respectively. Inhibition of these important UGT isoforms in human liver might be an important reason for clinically frequent drug-drug interaction between tacro and other drugs.
C1 [Sun, Xu-Yong] PLA, Dept Organ Transplantat, Hosp 303, Dalian, Peoples R China.
[Fang, Zhong-Ze] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Dong, Pei-Pei] Dalian Med Univ, Res Inst Integrated Tradit & Western Med, Dalian, Peoples R China.
[Teng, Yan-Jie] Mudanjiang Med Coll, Dept Pathophysiol, Mudanjiang, Heilongjiang, Peoples R China.
RP Sun, XY (reprint author), PLA, Dept Organ Transplantat, Hosp 303, Dalian, Peoples R China.
EM sxywn@sohu.com
NR 23
TC 12
Z9 12
U1 0
U2 9
PU GOVI-VERLAG PHARMAZEUTISCHER VERLAG GMBH
PI ESCHBORN
PA PHARMAZEUTISCCARL MANNICH STR 26, D-65760 ESCHBORN, GERMANY
SN 0031-7144
J9 PHARMAZIE
JI Pharmazie
PD SEP
PY 2012
VL 67
IS 9
BP 804
EP 808
DI 10.1691/ph.2012.2509
PG 5
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology &
Pharmacy
SC Pharmacology & Pharmacy; Chemistry
GA 006WR
UT WOS:000308851000011
PM 23016456
ER
PT J
AU Singh, T
Chaudhary, SC
Kapur, P
Weng, ZP
Elmets, CA
Kopelovich, L
Athar, M
AF Singh, Tripti
Chaudhary, Sandeep C.
Kapur, Puneet
Weng, Zhiping
Elmets, Craig A.
Kopelovich, Levy
Athar, Mohammad
TI Nitric Oxide Donor Exisulind Is an Effective Inhibitor of Murine
Photocarcinogenesis
SO PHOTOCHEMISTRY AND PHOTOBIOLOGY
LA English
DT Article
ID SKH-1 HAIRLESS MICE; COLON-CANCER CELLS; SIGNALING PATHWAYS; TUMOR
PROGRESSION; IN-VITRO; SKIN; EXPRESSION; SULINDAC; METABOLITES;
CARCINOMA
AB NO-releasing nonsteroidal anti-inflammatory drugs (NO-NSAIDs) have been shown to have anti-inflammatory, antiproliferative and apoptosis-inducing effects in tumor cells. Herein, we have investigated the effects of NO-exisulind on the growth of UVB-induced skin tumor development in a murine model. We found that the topical treatment with NO-exisulind significantly reduced UVB-induced tumors in SKH-1 hairless mice. The tumors/tumor bearing mouse, the number of tumors/mouse and tumor volume/mouse decreased significantly (P < 0.05) as compared with vehicle-treated and UVB-irradiated positive controls. Consistently, NO-exisulind-treated animals showed reduced expression of proliferation markers, such as PCNA and cyclin D1. These mice also manifested increased expression of proapoptotic Bax and decreased expression of antiapoptotic Bcl2 with an increase in the number of TUNEL-positive cells in tumors. We also investigated whether NO-exisulind-treated tumors are less invasive and progress less efficiently from benign to malignant carcinomas. For this, tumors were stained for various epithelial-mesenchymal transition (EMT) markers. NO-exisulind decreased the expression of mesenchymal markers, such as Fibronectin, N-cadherin, SNAI, Slug and Twist and enhanced the epithelial marker E-cadherin. Similarly, UVB-induced phosphorylation of Erk1/2 and p38 was decreased in NO-exisulind-treated animals. These data suggest that NO-exisulind reduces tumor growth and inhibits tumor progression by blocking proliferation, inducing apoptosis and reducing EMT.
C1 [Singh, Tripti; Chaudhary, Sandeep C.; Kapur, Puneet; Weng, Zhiping; Elmets, Craig A.; Athar, Mohammad] Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA.
[Kopelovich, Levy] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Athar, M (reprint author), Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA.
EM mathar@uab.edu
FU [N01-CN-43300]; [R01CA138998]
FX This work has been supported in part by N01-CN-43300 and R01CA138998 to
Dr. Athar.
NR 34
TC 2
Z9 2
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0031-8655
EI 1751-1097
J9 PHOTOCHEM PHOTOBIOL
JI Photochem. Photobiol.
PD SEP-OCT
PY 2012
VL 88
IS 5
BP 1141
EP 1148
DI 10.1111/j.1751-1097.2012.01093.x
PG 8
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 000OM
UT WOS:000308396000011
PM 22364235
ER
PT J
AU Chaudhary, SC
Kurundkar, D
Elmets, CA
Kopelovich, L
Athar, M
AF Chaudhary, Sandeep C.
Kurundkar, Deepali
Elmets, Craig A.
Kopelovich, Levy
Athar, Mohammad
TI Metformin, an Antidiabetic Agent Reduces Growth of Cutaneous Squamous
Cell Carcinoma by Targeting mTOR Signaling Pathway
SO PHOTOCHEMISTRY AND PHOTOBIOLOGY
LA English
DT Article
ID CANCER PREVENTION; MAMMALIAN TARGET; PROTEIN-KINASE; SKIN-CANCER;
RAPAMYCIN; INSULIN; TUMORIGENESIS; INHIBITION; APOPTOSIS; THERAPY
AB The biguanide metformin is widely used for the treatment of Type-II diabetes. Its antiproliferative and pro-apoptotic effects in various tumor cells suggest its potential candidacy for cancer chemoprevention. Herein, we report that metformin significantly inhibited human epidermoid A431 tumor xenograft growth in nu/nu mice, which was associated with a significant reduction in proliferative biomarkers PCNA and cyclins D1/B1. This tumor growth reduction was accompanied by the enhanced apoptotic cell death and an increase in Bax:Bcl2 ratio. The mechanism by which metformin manifests antitumor effects appears to be dependent on the inhibition of nuclear factor kappa B (NFkB) and mTOR signaling pathways. Decreased phosphorylation of NFkB inhibitory protein IKB alpha together with reduced enhancement of NFkB transcriptional target proteins, iNOS/COX-2 were observed. In addition, a decrease in the activation of ERK/p38-driven MAP kinase signaling was seen. Similarly, AKT signaling activation as assessed by the diminished phosphorylation at Ser473 with a concomitant decrease in mTOR signaling pathway was also noted as phosphorylation of mTOR regulatory proteins p70S6K and 4E-BP-1 was significantly reduced. Consistently, decreased phosphorylation of GSK3 beta, which is carried out by AKT kinases was also observed. These results suggest that metformin blocks SCC growth by dampening NFkB and mTOR signaling pathways.
C1 [Chaudhary, Sandeep C.; Kurundkar, Deepali; Elmets, Craig A.; Athar, Mohammad] Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA.
[Kopelovich, Levy] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Athar, M (reprint author), Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA.
EM mathar@uab.edu
FU [N01-CN-43300]; [R01CA138998]
FX This work has been supported in part by N01-CN-43300 and R01CA138998 to
Dr. Athar.
NR 42
TC 23
Z9 24
U1 1
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0031-8655
J9 PHOTOCHEM PHOTOBIOL
JI Photochem. Photobiol.
PD SEP-OCT
PY 2012
VL 88
IS 5
BP 1149
EP 1156
DI 10.1111/j.1751-1097.2012.01165.x
PG 8
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 000OM
UT WOS:000308396000012
PM 22540890
ER
PT J
AU Getreuer, P
Girardi, T
Li, YY
Salafia, C
Dalton, J
Katzman, P
Ruffolo, L
Miller, R
Moye, J
AF Getreuer, Pascal
Girardi, Theresa
Li, Yingying
Salafia, Carolyn
Dalton, Jeffrey
Katzman, Philip
Ruffolo, Luis
Miller, Richard
Moye, John
CA Vanguard Sites Natl Childrens
TI ACCURACY OF 2D AND 3D MEASUREMENT OF PLACENTA SHAPE
SO PLACENTA
LA English
DT Meeting Abstract
CT Meeting of the International-Federation-of-Placenta-Associations (IFPA)
CY SEP 18-21, 2012
CL Hiroshima, JAPAN
SP Int Federat Placenta Assoc (IFPA)
C1 [Getreuer, Pascal; Girardi, Theresa; Li, Yingying; Dalton, Jeffrey] Placental Analyt LLC, Larchmont, NY USA.
[Salafia, Carolyn; Katzman, Philip; Ruffolo, Luis; Miller, Richard] Univ Rochester, Sch Med & Dent, Rochester, NY USA.
[Moye, John] NICHHD, NIH, Bethesda, MD 20892 USA.
S Dakota State Univ, Pierre, SD USA.
Mt Sinai Sch Med, New York, NY 10029 USA.
Columbia Univ, New York, NY 10027 USA.
Univ Utah, Salt Lake City, UT 84112 USA.
Univ Calif Irvine, Irvine, CA 92717 USA.
Univ N Carolina, Chapel Hill, NC 27515 USA.
[Vanguard Sites Natl Childrens] Univ Wisconsin, Madison, WI 53706 USA.
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 2012
VL 33
IS 9
BP A22
EP A22
PG 1
WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
GA 007NV
UT WOS:000308896300057
ER
PT J
AU Girardi, T
Salafia, C
Getreuer, P
Li, YY
Dalton, J
VanHorn, S
Miller, R
Katzman, P
Ruffolo, L
Moye, J
AF Girardi, Theresa
Salafia, Carolyn
Getreuer, Pascal
Li, Yingying
Dalton, Jeffrey
VanHorn, Samantha
Miller, Richard
Katzman, Philip
Ruffolo, Luis
Moye, John
CA Vanguard Sites Natl Childrens
TI HOW TO SLICE THE PLACENTAL DISK - ONE-PROTOCOL-FITS-ALL OR A
SPECIMEN-SPECIFIC APPROACH?
SO PLACENTA
LA English
DT Meeting Abstract
CT Meeting of the International-Federation-of-Placenta-Associations (IFPA)
CY SEP 18-21, 2012
CL Hiroshima, JAPAN
SP Int Federat Placenta Assoc (IFPA)
C1 [Girardi, Theresa; Salafia, Carolyn; Getreuer, Pascal; Li, Yingying; Dalton, Jeffrey; VanHorn, Samantha] Placental Analyt LLC, Larchmont, NY USA.
[Miller, Richard; Katzman, Philip; Ruffolo, Luis] Univ Rochester, Sch Med & Dent, Rochester, NY USA.
[Moye, John] NICHHD, NIH, Bethesda, MD 20892 USA.
S Dakota State Univ, Pierre, SD USA.
Metropolitan Hosp Ctr, New York, NY 10029 USA.
Columbia Univ, New York, NY 10027 USA.
Univ Utah, Salt Lake City, UT 84112 USA.
Univ Calif Irvine, Irvine, CA 92717 USA.
Univ N Carolina, Chapel Hill, NC 27515 USA.
[Vanguard Sites Natl Childrens] Univ Wisconsin, Madison, WI 53706 USA.
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 2012
VL 33
IS 9
BP A23
EP A23
PG 1
WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
GA 007NV
UT WOS:000308896300058
ER
PT J
AU Li, YY
Salafia, C
Shlahkter, O
Getreuer, P
Misra, D
Katzman, P
Ruffolo, L
Moye, J
AF Li, Yingying
Salafia, Carolyn
Shlahkter, Oleksandr
Getreuer, Pascal
Misra, Dawn
Katzman, Philip
Ruffolo, Luis
Moye, John
CA Vanguard Sites Natl Childrens
TI THE CHORIONIC SURFACE VASCULAR NETWORK IN HUMAN PLACENTAE: WHAT CAN BE
MEASURED AND DOES IT MATTER?
SO PLACENTA
LA English
DT Meeting Abstract
CT Meeting of the International-Federation-of-Placenta-Associations (IFPA)
CY SEP 18-21, 2012
CL Hiroshima, JAPAN
SP Int Federat Placenta Assoc (IFPA)
C1 [Li, Yingying; Salafia, Carolyn; Shlahkter, Oleksandr; Getreuer, Pascal; Misra, Dawn] Placental Analyt LLC, Larchmont, NY 20892 USA.
[Katzman, Philip; Ruffolo, Luis] Univ Rochester, Sch Med & Dent, Rochester 57501, NY USA.
[Moye, John] NICHHD, NIH, Bethesda, MD 10029 USA.
S Dakota State Univ, Pierre Benite, 10027, France.
Mt Sinai Sch Med, New York, NY 84112 USA.
Columbia Univ, New York, NY 92717 USA.
Univ Utah, Salt Lake City, UT 53706 USA.
Univ Calif Irvine, Irvine, CA USA.
[Vanguard Sites Natl Childrens] Univ Wisconsin, Madison, WI USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 2012
VL 33
IS 9
BP A21
EP A21
PG 1
WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
GA 007NV
UT WOS:000308896300055
ER
PT J
AU Li, YY
Salafia, C
Getreuer, P
Misra, D
Katzman, P
Ruffolo, L
Miller, R
Moye, J
AF Li, Yingying
Salafia, Carolyn
Getreuer, Pascal
Misra, Dawn
Katzman, Philip
Ruffolo, Luis
Miller, Richard
Moye, John
CA Vanguard Sites Natl Children's
TI FRESH VERSUS FORMALIN FIXED HUMAN PLACENTAE: DOES PRESERVATION AFFECT
CHORIONIC PLATE MEASURES?
SO PLACENTA
LA English
DT Meeting Abstract
CT Meeting of the International-Federation-of-Placenta-Associations (IFPA)
CY SEP 18-21, 2012
CL Hiroshima, JAPAN
SP Int Federat Placenta Assoc (IFPA)
C1 [Li, Yingying; Salafia, Carolyn; Getreuer, Pascal; Misra, Dawn] Placental Analyt LLC, Larchmont, NY USA.
[Katzman, Philip; Ruffolo, Luis; Miller, Richard] Univ Rochester, Sch Med & Dent, Rochester, NY USA.
[Moye, John] NICHHD, NIH, Bethesda, MD 20892 USA.
S Dakota State Univ, Pierre, SD USA.
Mt Sinai Sch Med, New York, NY 10029 USA.
Columbia Univ, New York, NY 10027 USA.
Univ Utah, Salt Lake City, UT 84112 USA.
Univ Calif Irvine, Irvine, CA 92717 USA.
Univ N Carolina, Chapel Hill, NC 27515 USA.
[Vanguard Sites Natl Children's] Univ Wisconsin, Madison, WI 53706 USA.
NR 0
TC 0
Z9 0
U1 1
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 2012
VL 33
IS 9
BP A19
EP A19
PG 1
WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
GA 007NV
UT WOS:000308896300050
ER
PT J
AU Misra, D
Salafia, C
Getreuer, P
Li, YY
Katzman, P
Ruffolo, L
Miller, R
Moye, J
AF Misra, Dawn
Salafia, Carolyn
Getreuer, Pascal
Li, Yingying
Katzman, Philip
Ruffolo, Luis
Miller, Richard
Moye, John
CA Vanguard Sites Natl Childrens
TI COST-EFFECTIVE, REPRODUCIBLE, AND RELIABLE AUTOMATED DIAGNOSIS OF
INTRAAMNIOTIC INFECTION FOR POPULATION BASED RESEARCH FROM PLACENTAE IN
THE NATIONAL CHILDREN'S STUDY
SO PLACENTA
LA English
DT Meeting Abstract
CT Meeting of the International-Federation-of-Placenta-Associations (IFPA)
CY SEP 18-21, 2012
CL Hiroshima, JAPAN
SP Int Federat Placenta Assoc (IFPA)
C1 [Misra, Dawn] Wayne State Univ, Sch Med, Detroit, MI 48202 USA.
[Salafia, Carolyn; Getreuer, Pascal; Li, Yingying] Placental Analyt LLC, Larchmont, NY USA.
[Katzman, Philip; Ruffolo, Luis; Miller, Richard] Univ Rochester, Sch Med & Dent, Rochester, NY USA.
[Moye, John] NICHHD, NIH, Bethesda, MD 20892 USA.
S Dakota State Univ, Pierre, SD 57501 USA.
Mt Sinai Sch Med, New York, NY 10029 USA.
Columbia Univ, New York, NY 10027 USA.
Univ Utah, Salt Lake City, UT 84112 USA.
Univ Calif Irvine, Irvine, CA 92717 USA.
Univ N Carolina, Chapel Hill, NC 27515 USA.
[Vanguard Sites Natl Childrens] Univ Wisconsin, Madison, WI 53706 USA.
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 2012
VL 33
IS 9
BP A22
EP A22
PG 1
WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
GA 007NV
UT WOS:000308896300056
ER
PT J
AU Kamrava, M
Kesarwala, AH
Madan, RA
Lita, E
Kaushal, A
Tsang, KY
Poole, DJ
Steinberg, SM
Ferrara, T
Dahut, W
Schlom, J
Gulley, JL
AF Kamrava, M.
Kesarwala, A. H.
Madan, R. A.
Lita, E.
Kaushal, A.
Tsang, K-Y
Poole, D. J.
Steinberg, S. M.
Ferrara, T.
Dahut, W.
Schlom, J.
Gulley, J. L.
TI Long-term follow-up of prostate cancer patients treated with vaccine and
definitive radiation therapy
SO PROSTATE CANCER AND PROSTATIC DISEASES
LA English
DT Article
DE radiotherapy; therapeutic vaccine; immunotherapy; PROSTVAC
ID RANDOMIZED CONTROLLED-TRIAL; ANDROGEN SUPPRESSION; PHASE-II;
RADIOTHERAPY; ANTIGEN; ADJUVANT; ADENOCARCINOMA; BRACHYTHERAPY;
CARCINOMA; ERA
AB BACKGROUND: Vaccine therapy in combination with radiation therapy may improve distant and/or local control in prostate cancer. We present long-term follow-up data on the secondary and exploratory endpoints of safety and biochemical failure, respectively, from patients with clinically localized prostate cancer treated definitively with a poxviral vector-based therapeutic vaccine combined with external beam radiation therapy (EBRT).
METHODS: Thirty-six prostate cancer patients received definitive EBRT plus vaccine. A total of 18 patients were treated with adjuvant standard-dose interleukin-2 (S-IL-2) (4 MIU m(-2)) and 18 were treated with very low-dose IL-2 (M-IL-2) (0.6 MIU m(-2)). Seven patients were treated with EBRT alone. Twenty-six patients treated with EBRT plus vaccine returned for follow-up, and we reviewed the most recent labs and clinical notes of the remaining patients.
RESULTS: Median follow-up for the S-IL-2, M-IL-2 and EBRT-alone groups was 98, 76 and 79 months, respectively. Actuarial 5-year PSA failure-free probability was 78%, 82% and 86% (P = 0.58 overall), respectively. There were no significant differences between the actuarial overall survival and the prostate cancer-specific survival between the two vaccine arms. Of the 26 patients who returned for follow-up, Radiation Therapy Oncology Group grade >= 2 genitourinary (GU) and gastrointestinal (GI) toxicity was seen in 19% and 8%, respectively, with no difference between the arms (P = 1.00 and P = 0.48 for grade 2 GU and GI toxicity, respectively). In all, 12 patients were evaluated for PSA-specific immune responses, and 1 demonstrated a response 66 months post-enrollment.
CONCLUSIONS: We demonstrate that vaccine combined with EBRT does not appear to have significant differences with regard to PSA control or late-term toxicity compared with standard treatment. We also found limited evidence of long-term immune response following vaccine therapy.
C1 [Madan, R. A.; Tsang, K-Y; Poole, D. J.; Ferrara, T.; Schlom, J.; Gulley, J. L.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Kamrava, M.] Univ Calif Los Angeles, Dept Radiat Oncol, Los Angeles, CA 90024 USA.
[Kesarwala, A. H.; Lita, E.; Kaushal, A.] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Madan, R. A.; Dahut, W.; Gulley, J. L.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Steinberg, S. M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Gulley, JL (reprint author), NCI, Tumor Immunol & Biol Lab, 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
NR 23
TC 2
Z9 3
U1 0
U2 2
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 2012
VL 15
IS 3
BP 289
EP 295
DI 10.1038/pcan.2012.7
PG 7
WC Oncology; Urology & Nephrology
SC Oncology; Urology & Nephrology
GA 992SF
UT WOS:000307799300013
PM 22391584
ER
PT J
AU Goh, JO
An, Y
Resnick, SM
AF Goh, Joshua O.
An, Yang
Resnick, Susan M.
TI Differential Trajectories of Age-Related Changes in Components of
Executive and Memory Processes
SO PSYCHOLOGY AND AGING
LA English
DT Article
DE aging; executive function; memory; longitudinal; cross-sectional
ID ADULT LIFE-SPAN; AGING BRAIN-FUNCTION; OLDER-ADULTS;
INDIVIDUAL-DIFFERENCES; LONGITUDINAL CHANGES; HEALTHY-ADULTS;
CRYSTALLIZED INTELLIGENCE; COGNITIVE PERFORMANCE; RECOGNITION MEMORY;
ALZHEIMERS-DISEASE
AB Several studies have demonstrated age-related declines in general executive function and memory. In this study, we examined cross-sectional and longitudinal age effects in more specific cognitive processes that constitute executive function and memory. We postulated that, whereas some components of executive and memory functions would show age differences and longitudinal declines, other specific abilities would be maintained or even improve with repeated testing. In a sample of individuals >= 55 years old from the Baltimore Longitudinal Study of Aging, we found longitudinal declines in inhibition, manipulation, semantic retrieval, phonological retrieval, switching, and long-term memory over a maximum of 14 years follow-up. In contrast, abstraction, capacity, chunking, discrimination, and short-term memory were maintained or even improved longitudinally, probably due in part to repeated testing. Moreover, whereas several different abilities were correlated across participants' cross-sectional performance, longitudinal changes in performance showed more heterogeneous trajectories. Finally, compared with cross-sectional performance, longitudinal trajectories showed better distinction between participants with and those without later cognitive impairment. These results show that longitudinal cognitive aging of executive and memory functions is not a uniform process but a heterogeneous one and suggest that certain executive and memory functions remain stable despite age-related declines in other component processes.
C1 [Goh, Joshua O.; An, Yang; Resnick, Susan M.] NIA, Lab Behav Neurosci, Intramural Res Project, Bethesda, MD 20892 USA.
RP Goh, JO (reprint author), 251 Bayview Blvd,Suite 100,Room 4B316, Baltimore, MD 21224 USA.
EM joshua.goh@nih.gov
RI GOH, JOSHUA/C-8063-2016
OI GOH, JOSHUA/0000-0001-7808-5452
FU Intramural NIH HHS [ZIA AG000191-15, Z01 AG000191-11]
NR 80
TC 26
Z9 28
U1 2
U2 20
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0882-7974
EI 1939-1498
J9 PSYCHOL AGING
JI Psychol. Aging
PD SEP
PY 2012
VL 27
IS 3
BP 707
EP 719
DI 10.1037/a0026715
PG 13
WC Gerontology; Psychology, Developmental
SC Geriatrics & Gerontology; Psychology
GA 004KC
UT WOS:000308679600017
PM 22201331
ER
PT J
AU John-Aryankalayil, M
Palayoor, ST
Makinde, AY
Cerna, D
Simone, CB
Falduto, MT
Magnuson, SR
Coleman, CN
AF John-Aryankalayil, Molykutty
Palayoor, Sanjeewani T.
Makinde, Adeola Y.
Cerna, David
Simone, Charles B., II
Falduto, Michael T.
Magnuson, Scott R.
Coleman, C. Norman
TI Fractionated Radiation Alters Oncomir and Tumor Suppressor miRNAs in
Human Prostate Cancer Cells
SO RADIATION RESEARCH
LA English
DT Article
ID MICRORNA EXPRESSION PROFILES; HUMAN LUNG CANCERS; IONIZING-RADIATION;
RNA EXPRESSION; BREAST-CANCER; P53; LET-7; MIR-17-92; PROLIFERATION;
SENSITIVITY
AB We have previously demonstrated that prostate carcinoma cells exposed to fractionated radiation differentially expressed more genes compared to single-dose radiation. To understand the role of miRNA in regulation of radiation-induced gene expression, we analyzed miRNA expression in LNCaP, PC3 and DU145 prostate cancer cells treated with single-dose radiation and fractionated radiation by micro-array. Selected miRNAs were studied in RWPE-1 normal prostate epithelial cells by RT-PCR. Fractionated radiation significantly altered more miRNAs as compared to single-dose radiation. Downregulation of oncomiR-17-92 cluster was observed only in the p53 positive LNCaP and RWPE-1 cells treated with single-dose radiation and fractionated radiation. Comparison of miRNA and mRNA data by IPA target filter analysis revealed an inverse correlation between miR-17-92 cluster and several targets including TP53INP1 in p53 signaling pathway. The base level expressions of these miRNAs were significantly different among the cell lines and did not predict the radiation outcome. Tumor suppressor miR-34a and let-7 miRNAs were upregulated by fractionated radiation in radiosensitive LNCaP (p53 positive) and PC3 (p53-null) cells indicating that radiation-induced miRNA expression may not be regulated by p53 alone. Our data support the potential for using fractionated radiation to induce molecular targets and radiation-induced miRNAs may have a significant role in predicting radiosensitivity. (C) 2012 by Radiation Research Society
C1 [John-Aryankalayil, Molykutty; Palayoor, Sanjeewani T.; Makinde, Adeola Y.; Cerna, David; Simone, Charles B., II; Coleman, C. Norman] NCI, Radiat Oncol Branch, Ctr Canc Research, NIH, Bethesda, MD 20892 USA.
[Falduto, Michael T.; Magnuson, Scott R.] GenUs BioSyst Inc, Northbrook, IL USA.
RP John-Aryankalayil, M (reprint author), NCI, Radiat Oncol Branch, Ctr Canc Research, NIH, 900 Rockville Pike,Room B3 B 406,Bldg 10, Bethesda, MD 20892 USA.
EM aryankalayilm@mail.nih.gov
RI Jackson, Benjamin/C-4297-2012
FU NIH, National Cancer Institute, Center for Cancer Research
FX This study was supported by the intramural research program of the NIH,
National Cancer Institute, Center for Cancer Research. The authors would
like to thank Drs. James Mitchell and John Cook, Radiation Biology
Department, NCI, for the help with survival curve analysis and Dr. Uma
Shankavaram from Radiation Oncology Branch, NCI, for expert suggestions.
NR 58
TC 27
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U1 3
U2 11
PU RADIATION RESEARCH SOC
PI LAWRENCE
PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA
SN 0033-7587
J9 RADIAT RES
JI Radiat. Res.
PD SEP
PY 2012
VL 178
IS 3
BP 105
EP 117
DI 10.1667/RR2703.1
PG 13
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
Nuclear Medicine & Medical Imaging
GA 005UN
UT WOS:000308775700001
PM 22827214
ER
PT J
AU Schonfeld, SJ
Tsareva, YV
Preston, DL
Okatenko, PV
Gilbert, ES
Ron, E
Sokolnikov, ME
Koshurnikova, NA
AF Schonfeld, S. J.
Tsareva, Y. V.
Preston, D. L.
Okatenko, P. V.
Gilbert, E. S.
Ron, E.
Sokolnikov, M. E.
Koshurnikova, N. A.
TI Cancer Mortality Following In Utero Exposure Among Offspring of Female
Mayak Worker Cohort Members
SO RADIATION RESEARCH
LA English
DT Article
ID CHILDHOOD-CANCER; IONIZING-RADIATION; NUCLEAR WORKERS; YOUNG-CHILDREN;
RISK; IRRADIATION; DOSIMETRY; BORN
AB Little is known about long-term cancer risks following in utero radiation exposure. We evaluated the association between in utero radiation exposure and risk of solid cancer and leukemia mortality among 8,000 offspring, born from 1948-1988, of female workers at the Mayak Nuclear Facility in Ozyorsk, Russia. Mother's cumulative gamma radiation uterine dose during pregnancy served as a surrogate for fetal dose. We used Poisson regression methods to estimate relative risks (RRs) and 95% confidence intervals (CIs) of solid cancer and leukemia mortality associated with in utero radiation exposure and to quantify excess relative risks (ERRs) as a function of dose. Using currently available dosimetry information, 3,226 (40%) offspring were exposed in utero (mean dose = 54.5 mGy). Based on 75 deaths from solid cancers (28 exposed) and 12 (6 exposed) deaths from leukemia, in utero exposure status was not significantly associated with solid cancer: RR = 0.94, 95% CI 0.58 to 1.49; ERFt/Gy = -0.1 (95% CI < -0.1 to 4.1), or leukemia mortality; RR = 1.65, 95% CI 0.52 to 5.27; ERR/Gy = -0.8 (95% CI < -0.8 to 46.9). These initial results provide no evidence that low-dose gamma in utero radiation exposure increases solid cancer or leukemia mortality risk, but the data are not inconsistent with such an increase. As the offspring cohort is relatively young, subsequent analyses based on larger case numbers are expected to provide more precise estimates of adult cancer mortality risk following in utero exposure to ionizing radiation. (C) 2012 by Radiation Research Society
C1 [Schonfeld, S. J.; Gilbert, E. S.; Ron, E.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Tsareva, Y. V.; Okatenko, P. V.; Sokolnikov, M. E.; Koshurnikova, N. A.] So Urals Biophys Inst, Epidemiol Lab, Ozyorsk, Russia.
[Preston, D. L.] HiroSoft Int Corp, Eureka, CA USA.
RP Schonfeld, SJ (reprint author), Int Agcy Res Canc, Sect Environm & Radiat, 150 Cours Albert Thomas, F-69372 Lyon 08, France.
EM schonfes@mail.nih.gov
FU National Cancer Institute, National Institutes of Health; Joint
Coordinating Committee for Radiation Effects Research
FX This research was supported by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health. We thank E. K.
Vasilenko for access to the Mayak Workers Dosimetry System 2008 and the
U.S. Department of Energy (DOE) under the auspices of the Joint
Coordinating Committee for Radiation Effects Research, which supports
the dosimetry program.
NR 22
TC 11
Z9 12
U1 0
U2 6
PU RADIATION RESEARCH SOC
PI LAWRENCE
PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA
SN 0033-7587
J9 RADIAT RES
JI Radiat. Res.
PD SEP
PY 2012
VL 178
IS 3
BP 160
EP 165
DI 10.1667/RR2848.1
PG 6
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
Nuclear Medicine & Medical Imaging
GA 005UN
UT WOS:000308775700006
PM 22799629
ER
PT J
AU Egawa, H
Furukawa, K
Preston, D
Funamoto, S
Yonehara, S
Matsuo, T
Tokuoka, S
Suyama, A
Ozasa, K
Kodama, K
Mabuchi, K
AF Egawa, Hiromi
Furukawa, Kyoji
Preston, Dale
Funamoto, Sachiyo
Yonehara, Shuji
Matsuo, Takeshi
Tokuoka, Shoji
Suyama, Akihiko
Ozasa, Kotaro
Kodama, Kazunori
Mabuchi, Kiyohiko
TI Radiation and Smoking Effects on Lung Cancer Incidence by Histological
Types Among Atomic Bomb Survivors
SO RADIATION RESEARCH
LA English
DT Article
ID CIGARETTE-SMOKING; RESIDENTIAL RADON; HODGKINS-DISEASE; NEVER-SMOKERS;
JAPANESE MEN; RISK; EXPOSURE; TRENDS; WOMEN; AGE
AB While the risk of lung cancer associated separately with smoking and radiation exposure has been widely reported, it is not clear how smoking and radiation together contribute to the risk of specific lung cancer histological types. With individual smoking histories and radiation dose estimates, we characterized the joint effects of radiation and smoking on type-specific lung cancer rates among the Life Span Study cohort of Japanese atomic bomb survivors. Among 105,404 cohort subjects followed between 1958 and 1999, 1,803 first primary lung cancer incident cases were diagnosed and classified by histological type. Poisson regression methods were used to estimate excess relative risks under several interaction models.
Adenocarcinoma (636 cases), squamous-cell carcinoma (330) and small-cell carcinoma (194) made up 90% of the cases with known histology. Both smoking and radiation exposure significantly increased the risk of each major lung cancer histological type. Smoking-associated excess relative risks were significantly larger for small-cell and squamous-cell carcinomas than for adenocarcinoma. The gender-averaged excess relative risks per 1 Gy of radiation (for never-smokers at age 70 after radiation exposure at age 30) were estimated as 1.49 (95% confidence interval 0.1-4.6) for small-cell carcinoma, 0.75 (0.3-1.3) for adenocarcinoma, and 0.27 (0-1.5) for squamous-cell carcinoma. Under a model allowing radiation effects to vary with levels of smoking, the nature of the joint effect of smoking and radiation showed a similar pattern for different histological types in which the radiation-associated excess relative risk tended to be larger for moderate smokers than for heavy smokers. However, in contrast to analyses of all lung cancers as a group, such complicated interactions did not describe the data significantly better than either simple additive or multiplicative interaction models for any of the type-specific analyses. (C) 2012 by Radiation Research Society
C1 [Egawa, Hiromi] Hiroshima City Asa Hosp, Hiroshima, Japan.
[Furukawa, Kyoji; Funamoto, Sachiyo; Tokuoka, Shoji; Suyama, Akihiko; Ozasa, Kotaro; Kodama, Kazunori] Radiat Effects Res Fdn, Hiroshima, Japan.
[Furukawa, Kyoji; Funamoto, Sachiyo; Tokuoka, Shoji; Suyama, Akihiko; Ozasa, Kotaro; Kodama, Kazunori] Radiat Effects Res Fdn, Nagasaki, Japan.
Hirosoft Int, Eureka, CA USA.
[Yonehara, Shuji] Welf Assoc Onomichi Gen Hosp, Tokyo, Japan.
Nagasaki Hlth Promot Corp, Nagasaki, Japan.
[Mabuchi, Kiyohiko] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Furukawa, K (reprint author), 5-2 Hijiyama Pk,Minami Ku, Hiroshima, Japan.
EM furukawa@rerf.or.jp
FU Radiation Effects Research Foundation [RP1-94]; Hiroshima and Nagasaki,
Japan; U.S. National Cancer Institute intramural research program
[NO2CP-2009-00005]; Japanese Ministry of Health, Labour and Welfare;
U.S. Department of Energy; National Academy of Sciences
FX This work was supported by the Radiation Effects Research Foundation
(RP1-94), Hiroshima and Nagasaki, Japan, and the U.S. National Cancer
Institute intramural research program (NO2CP-2009-00005). The Radiation
Effects Research Foundation is a private nonprofit foundation funded by
the Japanese Ministry of Health, Labour and Welfare and the U.S.
Department of Energy, the latter in part through the National Academy of
Sciences.
NR 37
TC 11
Z9 14
U1 0
U2 9
PU RADIATION RESEARCH SOC
PI LAWRENCE
PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA
SN 0033-7587
J9 RADIAT RES
JI Radiat. Res.
PD SEP
PY 2012
VL 178
IS 3
BP 191
EP 201
DI 10.1667/RR2819.1
PG 11
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
Nuclear Medicine & Medical Imaging
GA 005UN
UT WOS:000308775700010
PM 22862780
ER
PT J
AU Nacif, MS
Kawel, N
Lee, JJ
Chen, XJ
Yao, JH
Zavodni, A
Sibley, CT
Lima, JAC
Liu, ST
Bluemke, DA
AF Nacif, Marcelo Souto
Kawel, Nadine
Lee, Jason J.
Chen, Xinjian
Yao, Jianhua
Zavodni, Anna
Sibley, Christopher T.
Lima, Joao A. C.
Liu, Songtao
Bluemke, David A.
TI Interstitial Myocardial Fibrosis Assessed as Extracellular Volume
Fraction with Low-Radiation-Dose Cardiac CT
SO RADIOLOGY
LA English
DT Article
ID MULTIDETECTOR COMPUTED-TOMOGRAPHY; MAGNETIC-RESONANCE; DILATED
CARDIOMYOPATHY; CONTRAST ENHANCEMENT; BLOOD-FLOW; INFARCTION;
QUANTIFICATION; HETEROGENEITY; CALCIUM; DISEASE
AB Purpose: To develop a cardiac computed tomographic (CT) method with which to determine extracellular volume (ECV) fraction, with cardiac magnetic resonance (MR) imaging as the reference standard.
Materials and Methods: Study participants provided written informed consent to participate in this institutional review board-approved study. ECV was measured in healthy subjects and patients with heart failure by using cardiac CT and cardiac MR imaging. Paired Student t test, linear regression analysis, and Pearson correlation analysis were used to determine the relationship between cardiac CT and MR imaging ECV values and clinical parameters.
Results: Twenty-four subjects were studied. There was good correlation between myocardial ECV measured at cardiac MR imaging and that measured at cardiac CT (r = 0.82, P < .001). As expected, ECV was higher in patients with heart failure than in healthy control subjects for both cardiac CT and cardiac MR imaging (P = .03, respectively). For both cardiac MR imaging and cardiac CT, ECV was positively associated with end diastolic and end systolic volume and inversely related to ejection fraction (P < .05 for all). Mean radiation dose was 1.98 mSv +/- 0.16 (standard deviation) for each cardiac CT acquisition.
Conclusion: ECV at cardiac CT and that at cardiac MR imaging showed good correlation, suggesting the potential for myocardial tissue characterization with cardiac CT. (C) RSNA, 2012
C1 [Nacif, Marcelo Souto; Kawel, Nadine; Lee, Jason J.; Chen, Xinjian; Yao, Jianhua; Zavodni, Anna; Sibley, Christopher T.; Liu, Songtao; Bluemke, David A.] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
[Nacif, Marcelo Souto; Sibley, Christopher T.; Lima, Joao A. C.] Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD USA.
[Sibley, Christopher T.; Liu, Songtao; Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, Mol Biomed Imaging Lab, Bethesda, MD USA.
RP Bluemke, DA (reprint author), NIH, Dept Radiol & Imaging Sci, Ctr Clin, 10 Ctr Dr,Bldg 10,Room 1C355, Bethesda, MD 20892 USA.
EM bluemked@nih.gov
RI Sibley, Christopher/C-9900-2013; Chen, Xinjian/E-8592-2016;
OI Bluemke, David/0000-0002-8323-8086
FU National Institutes of Health [EB000072-02, CL090019-02]
FX This research was supported by the National Institutes of Health
intramural program (EB000072-02 and CL090019-02).
NR 30
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U1 0
U2 3
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 2012
VL 264
IS 3
BP 876
EP 883
DI 10.1148/radiol.12112458
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 003XU
UT WOS:000308645500030
PM 22771879
ER
PT J
AU Harari, S
Torre, O
Cassandro, R
Taveira-DaSilva, AM
Moss, J
AF Harari, Sergio
Torre, Olga
Cassandro, Roberto
Taveira-DaSilva, Angelo M.
Moss, Joel
TI Bronchoscopic diagnosis of Langerhans cell histiocytosis and
lymphangioleiomyomatosis
SO RESPIRATORY MEDICINE
LA English
DT Article
DE Interstitial lung diseases; Fiberoptic bronchoscopy
ID BRONCHOALVEOLAR LAVAGE FLUID; PULMONARY-FUNCTION TESTS; CYSTIC
LUNG-DISEASES; HIGH-RESOLUTION CT; TRANSBRONCHIAL BIOPSY; TOMOGRAPHY;
SMOKING; ADULTS
AB Limited data are available regarding the role of bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBB) as diagnostic tools in pulmonary Langerhans' Cell Histiocytosis (LCH) and lymphangioleiomyomatosis (LAM).
The aim of this study was to review our experience regarding the value of these two techniques in the diagnosis of these cystic lung diseases.
Records of 452 patients with the presumptive diagnosis of interstitial lung disease were reviewed; 67 had a clinical-radiological diagnosis of either LCH (n = 27) or LAM (n = 40). Of 16 patients with LCH who underwent BAL, four specimens (25%) contained cells which had positive immunoreactivity for CD1a. Of three patients with negative BAL fluid who had TBB, only one had a positive tissue diagnosis. Ten LCH patients were diagnosed by surgical lung biopsy of which five had negative BAL fluid. The remaining 12 patients were diagnosed by clinical and radiologic features. Standard examination of BAL fluid was of no diagnostic value in LAM. TBB was performed in seven patients and was diagnostic in six, not resulting in complications. All 13 patients who underwent surgical lung biopsies had a positive histopathologic diagnosis The remaining 21 patients were diagnosed by clinical and radiologic features. We suggest that BAL may assist in the diagnosis of LCH whereas TBB may be useful in the diagnosis of LAM, thus avoiding the need for surgical biopsy. (C) 2012 Published by Elsevier Ltd.
C1 [Taveira-DaSilva, Angelo M.; Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
[Harari, Sergio; Torre, Olga; Cassandro, Roberto] Osped San Giuseppe AFAR, Unita Pneumol & Terapia Semiintens Resp, Serv Fisiopatol Resp & Emodinam Polmonare, I-20123 Milan, Italy.
RP Taveira-DaSilva, AM (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10,Room 6D05,MSC 1590, Bethesda, MD 20892 USA.
EM sharari@ilpolmone.it; Olga.Torre@libero.it; rcassandro@hotmail.com;
dasilvaa@nhlbi.nih.gov; mossj@nhlbi.nih.gov
OI Harari, Sergio/0000-0001-8629-7391
FU Intramural Research Program, National Institutes of Health, National
Heart, Lung, and Blood Institute
FX Supported in part by the Intramural Research Program, National
Institutes of Health, National Heart, Lung, and Blood Institute.
NR 31
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Z9 13
U1 0
U2 4
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0954-6111
J9 RESP MED
JI Respir. Med.
PD SEP
PY 2012
VL 106
IS 9
BP 1286
EP 1292
DI 10.1016/j.rmed.2012.06.012
PG 7
WC Cardiac & Cardiovascular Systems; Respiratory System
SC Cardiovascular System & Cardiology; Respiratory System
GA 005RT
UT WOS:000308768300010
PM 22770823
ER
PT J
AU Poma, HR
Cacciabue, DG
Garce, B
Gonzo, EE
Rajal, VB
AF Ramiro Poma, Hugo
Gutierrez Cacciabue, Dolores
Garce, Beatriz
Emilio Gonzo, Elio
Beatriz Rajal, Veronica
TI Towards a rational strategy for monitoring of microbiological quality of
ambient waters
SO SCIENCE OF THE TOTAL ENVIRONMENT
LA English
DT Article
DE Water quality; Enteric virus; Parasite; Microbial indicator;
Surveillance strategy; PP7
ID REVERSE TRANSCRIPTION-PCR; DRINKING-WATER; RIVER WATER;
CRYPTOSPORIDIUM-OOCYSTS; SURFACE-WATER; WASTE-WATER; NESTED-PCR;
ENCEPHALITOZOON-INTESTINALIS; ENTEROCYTOZOON-BIENEUSI; RECREATIONAL
WATERS
AB Water is one of the main sources of human exposure to microbiological hazards. Although legislation establishes regulatory standards in terms of fecal indicator bacteria to assess the microbiological quality of water, these do not necessarily predict the presence of pathogens such as parasites and viruses. Better surveillance and management strategies are needed to assess the risk of pathogens' waterborne transmission. We established a baseline dataset to characterize river water quality, identify changes over time, and design a rational monitoring strategy. Data from a year-long monthly monitoring campaign of the polluted Arenales River (Argentina), were analyzed to statistically correlate physicochemical and microbiological variables, the seasonal and longitudinal variations of the water quality and determine the similarity between study sites. The measured variables (sixteen) reflected the deterioration in the river quality through the city. Different viruses and parasites found did not correlate with the concentration of total and thermotolerant coliforms. There was significant seasonal variation for temperature, turbidity, conductivity, dissolved oxygen, enterococci, and norovirus. Strong correlations between some variables were found; we selected eight variables (dissolved oxygen, conductivity, turbidity, total and thermotolerant coliforms, Enterococcus, and adenovirus and Microsporidium as viral and parasitological indicators, respectively) for future monitoring. There was similarity between the monitoring locations, which were grouped into four clusters validated by cophenetic correlation and supported by discriminant analysis. This allowed us to reduce the number of sites, from eleven down to five. Sixty seven percent of the total variance and the correlation structure between variables were explained using five principal components. All these analyses led to a new long-term systematic monitoring scheme. A rational monitoring strategy based on the selection of the most suitable monitoring points and of the most significant variables to measure, will result in optimal use of the limited resources available to adequately protect the public and environmental health. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Ramiro Poma, Hugo; Gutierrez Cacciabue, Dolores; Garce, Beatriz; Emilio Gonzo, Elio; Beatriz Rajal, Veronica] Univ Nacl Salta, INIQUI CONICET, RA-4400 Salta, Argentina.
[Beatriz Rajal, Veronica] Univ Calif Davis, Fogarty Int Ctr, CCRBM, Davis, CA 95616 USA.
RP Rajal, VB (reprint author), Univ Nacl Salta, INIQUI CONICET, Av Bolivia 5150, RA-4400 Salta, Argentina.
EM vbrajal@gmail.com
FU Agencia Nacional de Promocion de Ciencia y Tecnica in Argentina (ANPCyT)
[PICT-Red 276/06]; NIH [D43 TW005718]; Fogarty International Center from
the University of California at Davis; National Institute of
Environmental Health Sciences; CONICET
FX This research was part of project PICT-Red 276/06 funded by the Agencia
Nacional de Promocion de Ciencia y Tecnica in Argentina (ANPCyT). This
project was partially supported by NIH Grant # D43 TW005718 funded by
the Fogarty International Center from the University of California at
Davis and the National Institute of Environmental Health Sciences. Hugo
Ramiro Poma and Dolores Gutierrez Cacciabue are recipients of graduate
fellowships from CONICET. The authors would like to thank Dr. Jerold
Last for his kind help with the English corrections.
NR 108
TC 16
Z9 20
U1 0
U2 33
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0048-9697
J9 SCI TOTAL ENVIRON
JI Sci. Total Environ.
PD SEP 1
PY 2012
VL 433
BP 98
EP 109
DI 10.1016/j.scitotenv.2012.06.019
PG 12
WC Environmental Sciences
SC Environmental Sciences & Ecology
GA 005ZA
UT WOS:000308787500010
PM 22771467
ER
PT J
AU Deziel, NC
Nuckols, JR
Colt, JS
De Roos, AJ
Pronk, A
Gourley, C
Severson, RK
Cozen, W
Cerhan, JR
Hartge, P
Ward, MH
AF Deziel, N. C.
Nuckols, J. R.
Colt, J. S.
De Roos, A. J.
Pronk, A.
Gourley, C.
Severson, R. K.
Cozen, W.
Cerhan, J. R.
Hartge, P.
Ward, M. H.
TI Determinants of polychlorinated dibenzo-p-dioxins and polychlorinated
dibenzofurans in house dust samples from four areas of the United States
SO SCIENCE OF THE TOTAL ENVIRONMENT
LA English
DT Article
DE Dioxins; Furans; Geographic information systems; Dust; Environmental
exposure; Non-Hodgkin lymphoma (NHL)
ID SOLID-WASTE INCINERATOR; NON-HODGKINS-LYMPHOMA; ATTIC DUST; CARPET DUST;
RISK; EMISSIONS; HEALTH; CANCER; PCDDS; PCDFS
AB Determinants of levels of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/F) in dust in U.S. homes are not well characterized. We conducted a pilot study to evaluate the relationship between concentrations of PCDD/F in house dust and residential proximity to known sources, including industrial facilities and traffic. Samples from vacuum bag dust from homes of 40 residents of Detroit. Los Angeles, Seattle, or Iowa who participated in a population-based case-control study of non-Hodgkin lymphoma conducted in 1998-2000 were analyzed using high resolution gas chromatography/high resolution mass spectrometry for 7 PCDD and 10 PCDF congeners considered toxic by the U.S. Environmental Protection Agency (EPA). Locations of 10 types of PCDD/F-emitting facilities were obtained from the EPA; however only 4 types were located near study homes (non-hazardous waste cement kilns, coal-fired power plants, sewage sludge incinerators, and medical waste incinerators). Relationships between concentrations of each PCDD/F and proximity to industrial facilities, freight routes, and major roads were evaluated using separate multivariate regression models for each congener. The median (inter-quartile range [IQR]) toxic equivalence (TEQ) concentration of these congeners in the house dust was 20.3 pg/g (IQR = 14.3, 32.7). Homes within 3 or 5 km of a cement kiln had 2 to 9-fold higher concentrations of 5 PCDD and 5 PCDF (p<0.1 in each model). Proximity to freight routes and major roads was associated with elevated concentrations of 1 PCDD and 8 PCDF. Higher concentrations of certain PCDD/F in homes near cement kilns, freight routes, and major roads suggest that these outdoor sources are contributing to indoor environmental exposures. Further study of the contribution of these sources and other facility types to total PCDD/F exposure in a larger number of homes is warranted. Published by Elsevier B.V.
C1 [Deziel, N. C.; Colt, J. S.; Pronk, A.; Hartge, P.; Ward, M. H.] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Rockville, MD USA.
[Nuckols, J. R.] Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA.
[De Roos, A. J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[De Roos, A. J.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Pronk, A.] TNO, Dept Res & Dev, Org Appl Sci Res, NL-3700 AJ Zeist, Netherlands.
[Gourley, C.] SW Res Inst, San Antonio, TX USA.
[Severson, R. K.] Wayne State Univ, Dept Family Med, Detroit, MI USA.
[Severson, R. K.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
[Cozen, W.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Cerhan, J. R.] Mayo Clin, Dept Hlth Sci Res, Coll Med, Rochester, MN USA.
RP Deziel, NC (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8111, Bethesda, MD 20892 USA.
EM dezielnc@mail.nih.gov
OI Cerhan, James/0000-0002-7482-178X
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute
(NCI), National Institutes of Health; NCI-Iowa SEER [N01-CN-67008];
NCI-Los Angeles County SEER [N01-CN-67010]; NCI-Seattle SEER
[N01-PC-67009]; NCI-Detroit SEER [N01-PC-65064]
FX This study was supported by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics, National Cancer Institute
(NCI), National Institutes of Health; NCI-Iowa SEER contract
N01-CN-67008; NCI-Los Angeles County SEER contract N01-CN-67010;
NCI-Seattle SEER contract N01-PC-67009; and NCI-Detroit SEER contract
N01-PC-65064. Dr. John Nuckols was supported, in part, through an
intergovernmental personnel agreement between the NCI Occupational and
Environmental Epidemiology Branch and Colorado State University. We
thank Mr. Matt Airola of Westat for GIS support, Ms. Lonn Irish of
Information Management Systems, Inc. for programming support, and all
the study staff and participants.
NR 47
TC 8
Z9 9
U1 2
U2 33
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0048-9697
J9 SCI TOTAL ENVIRON
JI Sci. Total Environ.
PD SEP 1
PY 2012
VL 433
BP 516
EP 522
DI 10.1016/j.scitotenv.2012.06.098
PG 7
WC Environmental Sciences
SC Environmental Sciences & Ecology
GA 005ZA
UT WOS:000308787500056
PM 22832089
ER
PT J
AU Song, SS
Latour, LL
Ritter, CH
Wu, O
Tighiouart, M
Hernandez, DA
Ku, KD
Luby, M
Warach, S
AF Song, Shlee S.
Latour, Lawrence L.
Ritter, Carsten H.
Wu, Ona
Tighiouart, Mourad
Hernandez, Daymara A.
Ku, Katherine D.
Luby, Marie
Warach, Steven
TI A Pragmatic Approach Using Magnetic Resonance Imaging to Treat Ischemic
Strokes of Unknown Onset Time in a Thrombolytic Trial
SO STROKE
LA English
DT Article
DE diffusion-weighted imaging; fluid-attenuated inversion recovery; stroke;
thrombolysis
ID TISSUE-PLASMINOGEN ACTIVATOR; WAKE-UP; SYMPTOM ONSET; ABESTT-II;
HEMIANESTHESIA; EXPERIENCE; HEMIANOPIA; THERAPY; NEGLECT; MRI
AB Background and Purpose-Toward the goal of designing a clinical trial using imaging parameters to treat stroke patients with unknown onset time, we investigated the timing of changes on MRI in patients with well-defined stroke onset.
Methods-Hypothesis-generating (n=85) and confirmatory (n=111) samples were scored by blinded readers for fluid-attenuated inversion recovery (FLAIR) hyperintensity in diffusion-positive regions. Reader-measured signal intensity ratio (SIR) of the lesion to contralateral tissue was compared with SIR measured by coregistration.
Results-Lesion conspicuity increased with time on FLAIR (P=0.006). Qualitative assessment of FLAIR-negative vs FLAIR hyperintensity (k=0.7091; 95% CI, 0.61-0.81) showed good interrater agreement. Subtle hyperintensity was less reliably categorized (k=0.59; 95% CI, 0.47-0.71). Reader-measured SIR <1.15 can identify patients within the treatable time window of 4.5 hours (positive predictive value=0.90). The SIR was greater for right hemisphere lesions (P=0.04) for a given reported time from stroke symptom onset.
Conclusion-The SIR on FLAIR provides a quantitative tool to identify early ischemic strokes. In developing SIR thresholds, right hemisphere lesions may confound the accurate estimate of stroke onset time. Image coregistration for thrombolytic trial enrollment is not necessary. A SIR <1.15 on FLAIR yields a practical estimate of stroke onset within 4.5 hours. (Stroke. 2012;43:2331-2335.)
C1 [Song, Shlee S.] Cedars Sinai Med Ctr, Dept Neurol, Stroke Program, Los Angeles, CA 90048 USA.
[Song, Shlee S.; Latour, Lawrence L.; Ritter, Carsten H.; Hernandez, Daymara A.; Ku, Katherine D.; Luby, Marie; Warach, Steven] NINDS, Sect Stroke Diagnost & Therapeut, NIH, Bethesda, MD 20892 USA.
[Wu, Ona] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA.
[Tighiouart, Mourad] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst3, Los Angeles, CA 90048 USA.
[Warach, Steven] Univ Texas Austin, SW Med Ctr, Clin Res Inst, Austin Programs, Austin, TX 78712 USA.
RP Song, SS (reprint author), Cedars Sinai Med Ctr, Dept Neurol, Stroke Program, 8730 Alden Dr,Thalians E-216, Los Angeles, CA 90048 USA.
EM shlee.song@cshs.org
FU National Institutes of Health, National Institutes of Neurological
Diseases and Stroke
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institutes of Neurological
Diseases and Stroke.
NR 18
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U1 2
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD SEP
PY 2012
VL 43
IS 9
BP 2331
EP 2335
DI 10.1161/STROKEAHA.111.630947
PG 5
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 000UX
UT WOS:000308416300026
PM 22693129
ER
PT J
AU Weber, R
Weimar, C
Blatchford, J
Hermansson, K
Wanke, I
Moller-Hartmann, C
Gizewski, ER
Forsting, M
Demchuk, AM
Sacco, RL
Saver, JL
Warach, S
Diener, HC
Diehl, A
AF Weber, Ralph
Weimar, Christian
Blatchford, Jon
Hermansson, Karin
Wanke, Isabel
Moeller-Hartmann, Claudia
Gizewski, Elke R.
Forsting, Michael
Demchuk, Andrew M.
Sacco, Ralph L.
Saver, Jeffrey L.
Warach, Steven
Diener, Hans-Christoph
Diehl, Anke
CA PRoFESS Imaging Substudy Grp
TI Telmisartan on Top of Antihypertensive Treatment Does Not Prevent
Progression of Cerebral White Matter Lesions in the Prevention Regimen
for Effectively Avoiding Second Strokes (PRoFESS) MRI Substudy
SO STROKE
LA English
DT Article
DE antihypertensive treatment; cerebral small vessel disease; ischemic
stroke; magnetic resonance imaging; secondary prevention; telmisartan;
white matter lesion
ID EXTENDED-RELEASE DIPYRIDAMOLE; SMALL-VESSEL DISEASE; BLOOD-PRESSURE;
RECURRENT STROKE; ROTTERDAM SCAN; HYPERINTENSITY VOLUME; ELDERLY-PEOPLE;
HYPERTENSION; LEUKOARAIOSIS; PATHOGENESIS
AB Background and Purpose-High blood pressure is one of the main risk factors for cerebral white matter lesions (WMLs). There is limited evidence from one randomized trial that blood pressure-lowering is able to slow WML progression. We investigated whether telmisartan prevents WML progression in the imaging substudy of the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial.
Methods-This predefined substudy comprised 771 patients (mean age, 65 years) with recent ischemic stroke of noncardioembolic origin who received telmisartan or placebo during a mean follow-up of 27.9 (SD, 7.6) months and had 2 evaluable MRI examinations after index stroke and at study closeout. All MRI scans were centrally adjudicated for progression of periventricular and subcortical WML by 2 neuroradiologists blinded to treatment allocation.
Results-Mean blood pressure was 3.0/1.3 mm Hg lower with telmisartan compared with placebo at follow-up MRI. There was no statistically significant difference in progression of the mean periventricular WML score (least squares mean difference, 0.14; 95% CI, -0.12 to 0.39; P=0.29) and mean subcortical WML diameter (least squares mean difference, -0.35 mm; 95% CI, -1.00 to 0.31 mm; P=0.30) during follow-up between patients on telmisartan and placebo.
Conclusions-Treatment with telmisartan on top of existing antihypertensive medication did not result in significant blood pressure-lowering and did not prevent the progression of WML in patients with a recent ischemic stroke in this patient cohort. Our analysis is limited by the relatively short follow-up period.
C1 [Weber, Ralph; Weimar, Christian; Diener, Hans-Christoph] Univ Duisburg Essen, Dept Neurol, D-45122 Essen, Germany.
[Wanke, Isabel; Moeller-Hartmann, Claudia; Gizewski, Elke R.; Forsting, Michael; Diehl, Anke] Univ Duisburg Essen, Dept Neuroradiol, D-45122 Essen, Germany.
[Blatchford, Jon] Boehringer Ingelheim Ltd, Bracknell, Berks, England.
[Hermansson, Karin] Boehringer Ingelheim AB, Stockholm, Sweden.
[Demchuk, Andrew M.] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada.
[Sacco, Ralph L.] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA.
[Saver, Jeffrey L.] Univ Calif Los Angeles, Los Angeles Stroke Ctr, Los Angeles, CA USA.
[Warach, Steven] NINDS, Stroke Diagnost & Therapeut Sect, NIH, Bethesda, MD 20892 USA.
RP Diener, HC (reprint author), Univ Duisburg Essen, Dept Neurol, Hufelandstr 55, D-45122 Essen, Germany.
EM hans.diener@uni-duisburg-essen.de
RI bladin, chris/B-9136-2013; Forsting, Michael/C-6925-2013; Demchuk,
Andrew/E-1103-2012;
OI Demchuk, Andrew/0000-0002-4930-7789; Blatchford,
Jon/0000-0001-9354-9657; Saver, Jeffrey/0000-0001-9141-2251; Ringleb,
Peter/0000-0002-5473-8671
FU Boehringer Ingelheim; National Institute of Neurological Disorders and
Stroke for the Northern Manhattan Study; Astra/Zeneca; GSK; Novartis;
Janssen-Cilag; Sanofi-Aventis
FX Boehringer Ingelheim sponsored and funded the PRoFESS trial and the
imaging substudy.; C.W. received honoraria for participation in clinical
trials, contribution to advisory boards, or oral presentations from
Bayer, Boehringer Ingelheim, Brainsgate, Bristol-Myers Squib, Co-Axia,
D-Pharm, Photothera, Sanofi-Aventis, Syngis, and Thrombogenics. He
served on the end point adjudication committee of the PRoFESS trial.
J.B. and K. H. are employees of Boehringer Ingelheim. A. M. D. received
honoraria for contribution to advisory boards or oral presentations from
Boehringer Ingelheim and Merck. R. L. S. received grants from the
National Institute of Neurological Disorders and Stroke for the Northern
Manhattan Study. He served as a consultant to Boehringer Ingelheim
during the conduct of the PRoFESS trial. J.L.S. is an employee of the
University of California, which received payments based on clinical
trial contracts for the number of subjects enrolled from Boehringer
Ingelheim and AGA Medical and received payments for faculty
participation on scientific advisory boards from AGA Medical. H.-C. D.
received honoraria for participation in clinical trials, contribution to
advisory boards, or oral presentations from Abbott, AstraZeneca, Bayer
Vital, BMS, Boehringer Ingelheim, CoAxia, D-Pharm, Fresenius,
GlaxoSmithKline, Janssen-Cilag, MSD, MindFrame, Novartis, Novo-Nordisk,
Paion, Parke-Davis, Pfizer, Sanofi-Aventis, Sankyo, Servier, Solvay,
Thrombogenics, Wyeth, and Yamaguchi. Financial support for research
projects was provided by Astra/Zeneca, GSK, Boehringer Ingelheim,
Novartis, Janssen-Cilag, and Sanofi-Aventis. A. D. received honoraria
for contribution to advisory boards or oral presentations from
Boehringer Ingelheim and Bristol-MyersSquib.
NR 30
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U1 1
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD SEP
PY 2012
VL 43
IS 9
BP 2336
EP +
DI 10.1161/STROKEAHA.111.648576
PG 9
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 000UX
UT WOS:000308416300027
PM 22738922
ER
PT J
AU Willey, JZ
Ortega-Gutierrez, S
Petersen, N
Khatri, P
Ford, AL
Rost, NS
Ali, LK
Gonzales, NR
Merino, JG
Meyer, BC
Marshall, RS
AF Willey, Joshua Z.
Ortega-Gutierrez, Santiago
Petersen, Nils
Khatri, Pooja
Ford, Andria L.
Rost, Natalia S.
Ali, Latisha K.
Gonzales, Nichole R.
Merino, Jose G.
Meyer, Brett C.
Marshall, Randolph S.
TI Impact of Acute Ischemic Stroke Treatment in Patients > 80 Years of Age
The Specialized Program of Translational Research in Acute Stroke
(SPOTRIAS) Consortium Experience
SO STROKE
LA English
DT Article
DE acute Rx; acute stroke; interventional neuroradiology
ID TISSUE-PLASMINOGEN ACTIVATOR; RANDOMIZED CONTROLLED-TRIAL; 80 YEARS OLD;
INTRAVENOUS THROMBOLYSIS; RT-PA; INTRAARTERIAL THROMBOLYSIS; ALTEPLASE;
GREATER-THAN-OR-EQUAL-TO-80; OCTOGENARIANS; REGISTRY
AB Background and Purpose-Few studies have addressed outcomes among patients >= 80 years treated with acute stroke therapy. In this study, we outline in-hospital outcomes in (1) patients >= 80 years compared with their younger counterparts; and (2) those over >80 years receiving intra-arterial therapy (IAT) compared with those treated with intravenous recombinant tissue-type plasminogen activator (IV rtPA).
Methods-Stroke centers within the Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) prospectively collected data on all patients treated with IV rtPA or IAT from January 1, 2005, to December 31, 2010. IAT was defined as receiving any endovascular therapy; IAT was further divided into bridging therapy when the patient received both IAT and IV rtPA and endovascular therapy alone. In-hospital mortality was compared in (1) all patients aged >= 80 years versus younger counterparts; and (2) IAT, bridging therapy, and endovascular therapy alone versus IV rtPA only among those age >= 80 years using multivariable logistic regression. An age-stratified analysis was also performed.
Results-A total of 3768 patients were included in the study; 3378 were treated with IV rtPA alone and 808 with IAT (383 with endovascular therapy alone and 425 with bridging therapy). Patients >= 80 years (n=1182) had a higher risk of in-hospital mortality compared with younger counterparts regardless of treatment modality (OR, 2.13; 95% CI, 1.60-2.84). When limited to those aged >= 80 years, IAT (OR, 0.95; 95% CI, 0.60-1.49), bridging therapy (OR, 0.82; 95% CI, 0.47-1.45), or endovascular therapy alone (OR, 1.15; 95% CI, 0.64-2.08) versus IV rtPA were not associated with increased in-hospital mortality.
Conclusions-IAT does not appear to increase the risk of in-hospital mortality among those aged >80 years compared with IV thrombolysis alone. (Stroke. 2012;43:2369-2375.)
C1 [Willey, Joshua Z.; Ortega-Gutierrez, Santiago; Petersen, Nils; Marshall, Randolph S.] Columbia Univ, Dept Neurol, New York, NY 10032 USA.
[Khatri, Pooja] Univ Cincinnati, Dept Neurol, Cincinnati, OH USA.
[Ford, Andria L.] Washington Univ, Dept Neurol, St Louis, MO USA.
[Rost, Natalia S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Ali, Latisha K.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA.
[Gonzales, Nichole R.] Univ Texas Houston, Dept Neurol, Houston, TX USA.
[Merino, Jose G.] NIH, Div Intramural Res, Bethesda, MD 20892 USA.
[Meyer, Brett C.] Univ Calif San Diego, Dept Neurol, San Diego, CA 92103 USA.
RP Willey, JZ (reprint author), Columbia Univ, Dept Neurol, 710 W 168th St,Box 30, New York, NY 10032 USA.
EM jzw2@columbia.edu
OI Merino, Jose/0000-0002-6676-0008
FU National Institutes of Neurological Diseases and Stroke [NINDS P50
NS049060]; NINDS [1K23 NS 073104-01A1]; National Institutes of Health
(NIH) [AG 31009]; Intramural Division of the National Institute of
Neurological Disorders and Stroke/NIH
FX SPOTRIAS is funded by the National Institutes of Neurological Diseases
and Stroke (NINDS P50 NS049060). Dr Willey was funded by NINDS 1K23 NS
073104-01A1 and the National Institutes of Health (NIH) Loan Repayment
Program (AG 31009). This work was funded in part by the Intramural
Division of the National Institute of Neurological Disorders and
Stroke/NIH.
NR 34
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U1 3
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD SEP
PY 2012
VL 43
IS 9
BP 2369
EP 2375
DI 10.1161/STROKEAHA.112.660993
PG 7
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 000UX
UT WOS:000308416300032
PM 22798327
ER
PT J
AU Wang, ZF
Tsai, LK
Munasinghe, J
Leng, Y
Fessler, EB
Chibane, F
Leeds, P
Chuang, DM
AF Wang, Zhifei
Tsai, Li-Kai
Munasinghe, Jeeva
Leng, Yan
Fessler, Emily Bame
Chibane, Fairouz
Leeds, Peter
Chuang, De-Maw
TI Chronic Valproate Treatment Enhances Postischemic Angiogenesis and
Promotes Functional Recovery in a Rat Model of Ischemic Stroke
SO STROKE
LA English
DT Article
DE angiogenesis; cerebral ischemia; hypoxia-inducible factor-1; matrix
metalloproteinase; MRI; valproate; vascular endothelial growth factor
ID ENDOTHELIAL-GROWTH-FACTOR; BLOOD-BRAIN-BARRIER; HYPOXIA-INDUCIBLE
FACTOR-1-ALPHA; FOCAL CEREBRAL-ISCHEMIA; HISTONE DEACETYLASES;
GENE-EXPRESSION; MATRIX METALLOPROTEINASES; CELL PROLIFERATION;
FACTOR-I; INHIBITION
AB Background and Purpose-Enhanced angiogenesis facilitates neurovascular remodeling processes and promotes brain functional recovery after stroke. Previous studies from our laboratory demonstrated that valproate (VPA), a histone deacetylase inhibitor, protects against experimental brain ischemia. The present study investigated whether VPA could enhance angiogenesis and promote long-term functional recovery after ischemic stroke.
Methods-Male rats underwent middle cerebral artery occlusion for 60 minutes followed by reperfusion for up to 14 days. Assessed parameters were: locomotor function through the Rotarod test; infarct volume through T2-weighted MRI; microvessel density through immunohistochemistry; relative cerebral blood flow through perfusion-weighted imaging; protein levels of proangiogenic factors through Western blotting; and matrix metalloproteinase-2/9 activities through gelatin zymography.
Results-Postischemic VPA treatment robustly improved the Rotarod performance of middle cerebral artery occlusion rats on Days 7 and 14 after ischemia and significantly reduced brain infarction on Day 14. Concurrently, VPA markedly enhanced microvessel density, facilitated endothelial cell proliferation, and increased relative cerebral blood flow in the ipsilateral cortex. The transcription factor hypoxia-inducible factor-1 alpha and its downstream proangiogenic factors, vascular endothelial growth factor and matrix metalloproteinase-2/9, were upregulated after middle cerebral artery occlusion and significantly potentiated by VPA in the ipsilateral cortex. Acetylation of histone-H3 and H4 was robustly increased by chronic VPA treatment. The beneficial effects of VPA on Rotarod performance and microvessel density were abolished by hypoxia-inducible factor-1 alpha inhibition.
Conclusions-Chronic VPA treatment enhances angiogenesis and promotes functional recovery after brain ischemia. These effects may involve histone deacetylase inhibition and upregulation of hypoxia-inducible factor-1 alpha and its downstream proangiogenic factors vascular endothelial growth factor and matrix metalloproteinase-2/9. (Stroke. 2012;43:2430-2436.)
C1 [Wang, Zhifei; Tsai, Li-Kai; Leng, Yan; Fessler, Emily Bame; Chibane, Fairouz; Leeds, Peter; Chuang, De-Maw] NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
[Munasinghe, Jeeva] NINDS, Mouse Imaging Facil, NIH, Bethesda, MD 20892 USA.
[Tsai, Li-Kai] Natl Taiwan Univ Hosp, Dept Neurol, Taipei, Taiwan.
[Tsai, Li-Kai] Natl Taiwan Univ Hosp, Stroke Ctr, Taipei, Taiwan.
[Tsai, Li-Kai] Natl Taiwan Univ, Coll Med, Taipei 10764, Taiwan.
RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, NIH, 10 Ctr Dr,MSC 1363, Bethesda, MD 20892 USA.
EM chuang@mail.nih.gov
RI Wang, Zhifei/I-2787-2013;
OI Tsai, Li-Kai/0000-0001-8420-6951
FU National Institute of Mental Health, National Institutes of Health; Hsu
family gift fund
FX This research was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health, and
by the Hsu family gift fund.
NR 39
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U1 1
U2 15
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD SEP
PY 2012
VL 43
IS 9
BP 2430
EP +
DI 10.1161/STROKEAHA.112.652545
PG 16
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 000UX
UT WOS:000308416300041
PM 22811460
ER
PT J
AU Bradfute, SB
Warfield, KL
Bray, M
AF Bradfute, Steven B.
Warfield, Kelly L.
Bray, Mike
TI Mouse Models for Filovirus Infections
SO VIRUSES-BASEL
LA English
DT Review
DE filovirus; Ebola; Marburg; mouse models; hemorrhagic fever
ID EBOLA-VIRUS-INFECTION; PROTECT GUINEA-PIGS; EQUINE ENCEPHALITIS-VIRUS;
T-CELL RESPONSES; ANTIBODY-DEPENDENT ENHANCEMENT; MARBURG
HEMORRHAGIC-FEVER; NONHUMAN-PRIMATES; POSTEXPOSURE PROTECTION; VACCINE
PROTECTS; MONOCLONAL-ANTIBODIES
AB The filoviruses marburg- and ebolaviruses can cause severe hemorrhagic fever (HF) in humans and nonhuman primates. Because many cases have occurred in geographical areas lacking a medical research infrastructure, most studies of the pathogenesis of filoviral HF, and all efforts to develop drugs and vaccines, have been carried out in biocontainment laboratories in non-endemic countries, using nonhuman primates (NHPs), guinea pigs and mice as animal models. NHPs appear to closely mirror filoviral HF in humans (based on limited clinical data), but only small numbers may be used in carefully regulated experiments; much research is therefore done in rodents. Because of their availability in large numbers and the existence of a wealth of reagents for biochemical and immunological testing, mice have become the preferred small animal model for filovirus research. Since the first experiments following the initial 1967 marburgvirus outbreak, wild-type or mouse-adapted viruses have been tested in immunocompetent or immunodeficient mice. In this paper, we review how these types of studies have been used to investigate the pathogenesis of filoviral disease, identify immune responses to infection and evaluate antiviral drugs and vaccines. We also discuss the strengths and weaknesses of murine models for filovirus research, and identify important questions for further study.
C1 [Bradfute, Steven B.] Univ New Mexico, Albuquerque, NM 87131 USA.
[Warfield, Kelly L.] Integrated Biotherapeut Inc, Vaccine Dev, Gaithersburg, MD 20878 USA.
[Bray, Mike] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA.
RP Bradfute, SB (reprint author), Univ New Mexico, Albuquerque, NM 87131 USA.
EM sbradfute@salud.unm.edu; kelly@integratedbiotherapeutics.com;
MBray@niaid.nih.gov
NR 158
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U1 0
U2 36
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1999-4915
J9 VIRUSES-BASEL
JI Viruses-Basel
PD SEP
PY 2012
VL 4
IS 9
BP 1477
EP 1508
DI 10.3390/v4091477
PG 32
WC Virology
SC Virology
GA 012XF
UT WOS:000309269300006
PM 23170168
ER
PT J
AU Clark, DV
Jahrling, PB
Lawler, JV
AF Clark, Danielle V.
Jahrling, Peter B.
Lawler, James V.
TI Clinical Management of Filovirus-Infected Patients
SO VIRUSES-BASEL
LA English
DT Review
DE Filoviruses; Ebola; Marburg; Clinical management; Treatment; Outbreak
ID EBOLA HEMORRHAGIC-FEVER; DISEASE SURVEILLANCE UPDATE; MARBURG-VIRUS
DISEASE; SURVIVING SEPSIS CAMPAIGN; SEPTIC SHOCK; OUTBREAK; CONGO;
GABON; EPIDEMIC; FEATURES
AB Filovirus infection presents many unique challenges to patient management. Currently no approved treatments are available, and the recommendations for supportive care are not evidence based. The austere clinical settings in which patients often present and the sporadic and at times explosive nature of filovirus outbreaks have effectively limited the information available to evaluate potential management strategies. This review will summarize the management approaches used in filovirus outbreaks and provide recommendations for collecting the information necessary for evaluating and potentially improving patient outcomes in the future.
C1 [Clark, Danielle V.; Jahrling, Peter B.] NIAID, NIH, Integrated Res Facil, Ft Detrick, MD USA.
[Lawler, James V.] USN, Med Res Ctr Frederick, Frederick, MD USA.
RP Clark, DV (reprint author), NIAID, NIH, Integrated Res Facil, Ft Detrick, MD USA.
EM Danielle.clark.ctr@med.navy.mil; jahrlingp@niaid.nih.gov;
james.lawler2@med.navy.mil
NR 115
TC 26
Z9 27
U1 0
U2 14
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1999-4915
J9 VIRUSES-BASEL
JI Viruses-Basel
PD SEP
PY 2012
VL 4
IS 9
BP 1668
EP 1686
DI 10.3390/v4091668
PG 19
WC Virology
SC Virology
GA 012XF
UT WOS:000309269300016
PM 23170178
ER
PT J
AU Ramalingam, D
Kieffer-Kwon, P
Ziegelbauer, JM
AF Ramalingam, Dhivya
Kieffer-Kwon, Philippe
Ziegelbauer, Joseph M.
TI Emerging Themes from EBV and KSHV microRNA Targets
SO VIRUSES-BASEL
LA English
DT Review
DE EBV; KSHV; HHV4; HHV8; miRNAs; microRNAs
ID SARCOMA-ASSOCIATED HERPESVIRUS; EPSTEIN-BARR-VIRUS; HUMAN
GAMMA-HERPESVIRUSES; B-CELL LYMPHOMAS; NF-KAPPA-B; ENCODED MICRORNA;
NASOPHARYNGEAL CARCINOMA; LYTIC REACTIVATION; VIRAL MIRNAS; EXPRESSION
AB EBV and KSHV are both gamma-herpesviruses which express multiple viral microRNAs. Various methods have been used to investigate the functions of these microRNAs, largely through identification of microRNA target genes. Surprisingly, these related viruses do not share significant sequence homology in their microRNAs. A number of reports have described functions of EBV and KSHV microRNA targets, however only three experimentally validated target genes have been shown to be targeted by microRNAs from both viruses. More sensitive methods to identify microRNA targets have predicted approximately 60% of host targets could be shared by EBV and KSHV microRNAs, but by targeting different sequences in the host targets. In this review, we explore the similarities of microRNA functions and targets of these related viruses.
C1 [Ramalingam, Dhivya; Kieffer-Kwon, Philippe; Ziegelbauer, Joseph M.] NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA.
RP Ziegelbauer, JM (reprint author), NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA.
EM dhivya.ramalingam@nih.gov; philippe.kieffer-kwon@nih.gov;
ziegelbauerjm@mail.nih.gov
OI Ziegelbauer, Joseph/0000-0001-6464-6941
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 80
TC 24
Z9 24
U1 0
U2 12
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1999-4915
J9 VIRUSES-BASEL
JI Viruses-Basel
PD SEP
PY 2012
VL 4
IS 9
BP 1687
EP 1710
DI 10.3390/v4091687
PG 24
WC Virology
SC Virology
GA 012XF
UT WOS:000309269300017
PM 23170179
ER
PT J
AU Punia, S
Rumery, KK
Yu, EA
Lambert, CM
Notkins, AL
Weaver, DR
AF Punia, Sohan
Rumery, Kyle K.
Yu, Elizabeth A.
Lambert, Christopher M.
Notkins, Abner L.
Weaver, David R.
TI Disruption of gene expression rhythms in mice lacking secretory vesicle
proteins IA-2 and IA-2 beta
SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
LA English
DT Article
DE circadian; suprachiasmatic nucleus; vasoactive intestinal peptide;
Prprn; Ptprn2
ID VASOACTIVE-INTESTINAL-PEPTIDE; PHOSPHATASE-LIKE PROTEIN; SUPRACHIASMATIC
CIRCADIAN CLOCK; DEPENDENT DIABETES-MELLITUS; TYROSINE-PHOSPHATASE;
INSULIN-SECRETION; TRANSMEMBRANE PROTEIN; TARGETED DISRUPTION;
PERIPHERAL-TISSUES; VPAC(2) RECEPTOR
AB Punia S, Rumery KK, Yu EA, Lambert CM, Notkins AL, Weaver DR. Disruption of gene expression rhythms in mice lacking secretory vesicle proteins IA-2 and IA-2 beta. Am J Physiol Endocrinol Metab 303: E762-E776, 2012. First published July 11, 2012; doi:10.1152/ajpendo.00513.2011.-Insulinoma-associated protein (IA)-2 and IA-2 beta are transmembrane proteins involved in neurotransmitter secretion. Mice with targeted disruption of both IA-2 and IA-2 beta (double-knockout, or DKO mice) have numerous endocrine and physiological disruptions, including disruption of circadian and diurnal rhythms. In the present study, we have assessed the impact of disruption of IA-2 and IA-2 beta on molecular rhythms in the brain and peripheral oscillators. We used in situ hybridization to assess molecular rhythms in the hypothalamic suprachiasmatic nuclei (SCN) of wild-type (WT) and DKO mice. The results indicate significant disruption of molecular rhythmicity in the SCN, which serves as the central pacemaker regulating circadian behavior. We also used quantitative PCR to assess gene expression rhythms in peripheral tissues of DKO, single-knockout, and WT mice. The results indicate significant attenuation of gene expression rhythms in several peripheral tissues of DKO mice but not in either single knockout. To distinguish whether this reduction in rhythmicity reflects defective oscillatory function in peripheral tissues or lack of entrainment of peripheral tissues, animals were injected with dexamethasone daily for 15 days, and then molecular rhythms were assessed throughout the day after discontinuation of injections. Dexamethasone injections improved gene expression rhythms in liver and heart of DKO mice. These results are consistent with the hypothesis that peripheral tissues of DKO mice have a functioning circadian clockwork, but rhythmicity is greatly reduced in the absence of robust, rhythmic physiological signals originating from the SCN. Thus, IA-2 and IA-2 beta play an important role in the regulation of circadian rhythms, likely through their participation in neurochemical communication among SCN neurons.
C1 [Rumery, Kyle K.; Yu, Elizabeth A.; Lambert, Christopher M.; Weaver, David R.] Univ Massachusetts, Dept Neurobiol, Sch Med, Worcester, MA 01605 USA.
[Punia, Sohan; Notkins, Abner L.] Natl Inst Dent & Craniofacial Res, Expt Med Sect, NIH, Bethesda, MD USA.
[Rumery, Kyle K.] Univ Massachusetts, Sch Med, Summer Undergrad Res Program, Worcester, MA 01605 USA.
[Yu, Elizabeth A.; Weaver, David R.] Univ Massachusetts, MD PhD Program, Sch Med, Worcester, MA 01605 USA.
[Weaver, David R.] Univ Massachusetts, Program Neurosci, Sch Med, Worcester, MA 01605 USA.
RP Weaver, DR (reprint author), Univ Massachusetts, Dept Neurobiol, Sch Med, LRB 723,364 Plantat St, Worcester, MA 01605 USA.
EM David.weaver@umassmed.edu
FU University of Massachusetts Center for Clinical and Translational
Science Award [NIH 8UL1TR000161]; intramural research program of the
National Institute of Dental and Craniofacial Research, National
Institutes of Health (NIH); NIH [NS-056125, 5R25HL-092610-03]; Summer
Undergraduate Research Program fellowship; Office of Research of the
University of Massachusetts Medical School while an undergraduate at St.
Olaf College, Northfield, MN
FX We are deeply indebted to Stephen P. Baker for extensive consultations
regarding statistical analysis of the data; his effort is supported by
the University of Massachusetts Center for Clinical and Translational
Science Award No. NIH 8UL1TR000161.; This work was supported by the
intramural research program of the National Institute of Dental and
Craniofacial Research, National Institutes of Health (NIH), and by NIH
Grant NS-056125 (to D. R. Weaver). K. K. Rumery was supported in part by
a Summer Undergraduate Research Program fellowship supported under NIH
Grant 5R25HL-092610-03 and by the Office of Research of the University
of Massachusetts Medical School while an undergraduate at St. Olaf
College, Northfield, MN.
NR 57
TC 3
Z9 3
U1 0
U2 2
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1849
J9 AM J PHYSIOL-ENDOC M
JI Am. J. Physiol.-Endocrinol. Metab.
PD SEP
PY 2012
VL 303
IS 6
BP E762
EP E776
PG 15
WC Endocrinology & Metabolism; Physiology
SC Endocrinology & Metabolism; Physiology
GA 009BB
UT WOS:000308999200008
PM 22785238
ER
PT J
AU Zhou, XM
Burg, MB
Ferraris, JD
AF Zhou, Xiaoming
Burg, Maurice B.
Ferraris, Joan D.
TI Water restriction increases renal inner medullary manganese superoxide
dismutase (MnSOD)
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Article
DE hypertonicity; Cu/ZnSOD; catalase; TNF-alpha; NADPH oxidase
ID TRANSCRIPTION FACTOR TONEBP/OREBP; OXYGEN SPECIES CONTRIBUTE;
NACL-INDUCED ACTIVATION; OXIDATIVE STRESS; COLLECTING DUCT; CELLS;
INDUCTION; KIDNEY; MICE; UREA
AB Zhou X, Burg MB, Ferraris JD. Water restriction increases renal inner medullary manganese superoxide dismutase (MnSOD). Am J Physiol Renal Physiol 303: F674-F680, 2012. First published June 20, 2012; doi: 10.1152/ajprenal.00076.2012.-Oxidative stress damages cells. NaCl and urea are high in renal medullary interstitial fluid, which is necessary to concentrate urine, but which causes oxidative stress by elevating reactive oxygen species (ROS). Here, we measured the antioxidant enzyme superoxide dismutases (SODs, MnSOD, and Cu/ZnSOD) and catalase in mouse kidney that might mitigate the oxidative stress. MnSOD protein increases progressively from the cortex to the inner medulla, following the gradient of increasing NaCl and urea. MnSOD activity increases proportionately, but MnSOD mRNA does not. Water restriction, which elevates renal medullary NaCl and urea, increases MnSOD protein, accompanied by a proportionate increase in MnSOD enzymatic activity in the inner medulla, but not in the cortex or the outer medulla. In contrast, Cu/ZnSOD and TNF-alpha (an important regulator of MnSOD) do not vary between the regions of the kidney, and expression of catalase protein actually decreases from the cortex to the inner medulla. Water restriction increases activity of mitochondrial enzymes that catalyze production of ROS in the inner medulla, but reduces NADPH oxidase activity there. We also examined the effect of high NaCl and urea on MnSOD in Madin-Darby canine kidney (MDCK) cells. High NaCl and high urea both increase MnSOD in MDCK cells. This increase in MnSOD protein apparently depends on the elevation of ROS since it is eliminated by the antioxidant N-acetylcysteine, and it occurs without raising osmolality when ROS are elevated by antimycin A or xanthine oxidase plus xanthine. We conclude that ROS, induced by high NaCl and urea, increase MnSOD activity in the renal inner medulla, which moderates oxidative stress.
C1 [Zhou, Xiaoming] Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA.
[Burg, Maurice B.; Ferraris, Joan D.] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
RP Zhou, XM (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM xiaoming.zhou@usuhs.edu
FU Uniformed Services University [RO83ZY]; Department of Defense;
Intramural Research Program of the National Heart, Lung, and Blood
Institute, National Institutes of Health, Department of Health and Human
Services
FX This study was supported by a grant from Uniformed Services University
(RO83ZY), Department of Defense, and the Intramural Research Program of
the National Heart, Lung, and Blood Institute, National Institutes of
Health, Department of Health and Human Services.
NR 39
TC 2
Z9 2
U1 0
U2 3
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1931-857X
J9 AM J PHYSIOL-RENAL
JI Am. J. Physiol.-Renal Physiol.
PD SEP
PY 2012
VL 303
IS 5
BP F674
EP F680
DI 10.1152/ajprenal.00076.2012
PG 7
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA 001LR
UT WOS:000308462700011
PM 22718889
ER
PT J
AU Krampitz, GW
Norton, JA
Poultsides, GA
Visser, BC
Sun, LX
Jensen, RT
AF Krampitz, Geoffrey W.
Norton, Jeffrey A.
Poultsides, George A.
Visser, Brendan C.
Sun, Lixian
Jensen, Robert T.
TI Lymph Nodes and Survival in Pancreatic Neuroendocrine Tumors
SO ARCHIVES OF SURGERY
LA English
DT Article
ID ZOLLINGER-ELLISON-SYNDROME; LONG-TERM SURVIVAL; ENDOCRINE NEOPLASIA
TYPE-1; ISLET CELL TUMORS; PROGNOSTIC-FACTORS; NATURAL-HISTORY;
SURGICAL-MANAGEMENT; AGGRESSIVE SURGERY; PREDICTIVE FACTORS; LIVER
METASTASES
AB Hypothesis: Lymph node metastases decrease survival in patients with pancreatic neuroendocrine tumors (pNETs).
Design: Prospective database searches. Setting: National Institutes of Health (NIH) and Stanford University Hospital (SUH).
Patients: A total of 326 patients underwent surgical exploration for pNETs at the NIH (n = 216) and SUH (n = 110).
Main Outcome Measures: Overall survival, diseaserelated survival, and time to development of liver metastases.
Results: Forty patients (12.3%) underwent enucleation and 305 (93.6%) underwent resection. Of the patients who underwent resection, 117 (35.9%) had partial pancreatectomy and 30 (9.2%) had a Whipple procedure. Forty-one patients also had liver resections, 21 had wedge resections, and 20 had lobectomies. Mean follow-up was 8.1 years (range, 0.3-28.6 years). The 10-year overall survival for patients with no metastases or lymph node metastases only was similar at 80%. As expected, patients with liver metastases had a significantly decreased 10-year survival of 30% (P < .001). The time to development of liver metastases was significantly reduced for patients with lymph node metastases alone compared with those with none (P < .001). For the NIH cohort with longer follow-up, disease-related survival was significantly different for those patients with no metastases, lymph node metastases alone, and liver metastases (P < .001). Extent of lymph node involvement in this subgroup showed that disease-related survival decreased as a function of the number of lymph nodes involved (P =. 004).
Conclusions: As expected, liver metastases decrease survival of patients with pNETs. Patients with lymph node metastases alone have a shorter time to the development of liver metastases that is dependent on the number of lymph nodes involved. With sufficient long-term follow-up, lymph node metastases decrease diseaserelated survival. Careful evaluation of number and extent of lymph node involvement is warranted in all surgical procedures for pNETs.
C1 [Krampitz, Geoffrey W.; Norton, Jeffrey A.; Poultsides, George A.; Visser, Brendan C.; Sun, Lixian] Stanford Univ, Sch Med, Dept Surg, Stanford, CA 94305 USA.
[Jensen, Robert T.] NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Norton, JA (reprint author), Stanford Univ, Sch Med, Dept Surg, 300 Pasteur Dr,H3591, Stanford, CA 94305 USA.
EM janorton@stanford.edu
FU Intramural NIH HHS [Z99 DK999999, ZIA DK053200-19]
NR 69
TC 24
Z9 26
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0004-0010
J9 ARCH SURG-CHICAGO
JI Arch. Surg.
PD SEP
PY 2012
VL 147
IS 9
BP 820
EP 827
PG 8
WC Surgery
SC Surgery
GA 007JD
UT WOS:000308883700011
PM 22987171
ER
PT J
AU Zhu, JW
AF Zhu, Jianwei
TI Mammalian cell protein expression for biopharmaceutical production
SO BIOTECHNOLOGY ADVANCES
LA English
DT Review
DE Mammalian cell; Protein expression; Biopharmaceutical development;
Manufacturing
ID HAMSTER OVARY CELLS; TRANSIENT GENE-EXPRESSION; MONOCLONAL-ANTIBODY
PRODUCTION; N-LINKED GLYCOSYLATION; RECOMBINANT CHO-CELLS; HIGH-LEVEL
EXPRESSION; CD8(+) T-CELLS; SERUM-FREE; IN-VIVO; CULTURE-CONDITIONS
AB Mammalian cell expression has become the dominant recombinant protein production system for clinical applications because of its capacity for post-translational modification and human protein-like molecular structure assembly. While expression and production have been fully developed and Chinese hamster ovary cells are used for the majority of products both on the market and in clinical development, significant progresses in developing and engineering new cell lines, introducing novel genetic mechanisms in expression. gene silencing, and gene targeting, have been reported in the last several years. With the latest analytical methods development, more attention is being devoted towards product quality including glycol profiling, which leads to better understanding the impact of culture condition during production. Additionally, transient gene expression technology platform plays more important role in biopharmaceutical early development stages. This review focused on the latest advancements in the field. especially in active areas such as expression systems, glycosylation impact factors, and transient gene expression. (C) 2011 Elsevier Inc. All rights reserved.
C1 NCI, Biopharmaceut Dev Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Zhu, JW (reprint author), NCI, Biopharmaceut Dev Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
EM zhujianwei@mail.nih.gov
NR 170
TC 97
Z9 106
U1 11
U2 165
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0734-9750
EI 1873-1899
J9 BIOTECHNOL ADV
JI Biotechnol. Adv.
PD SEP-OCT
PY 2012
VL 30
IS 5
SI SI
BP 1158
EP 1170
DI 10.1016/j.biotechadv.2011.08.022
PG 13
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 005TP
UT WOS:000308773300020
PM 21968146
ER
PT J
AU Safaeian, M
Ghosh, A
Porras, C
Lin, SW
Rodriguez, AC
Schiffman, M
Wacholder, S
Kemp, T
Gonzalez, P
Wentzensen, N
Esser, M
Meuree, A
Matys, K
Quint, W
van Doorn, LJ
Sherman, ME
Herrero, R
Pinto, LA
Hildesheim, A
AF Safaeian, Mahboobeh
Ghosh, Arpita
Porras, Carolina
Lin, Shih-Wen
Rodriguez, Ana Cecilia
Schiffman, Mark
Wacholder, Sholom
Kemp, Troy
Gonzalez, Paula
Wentzensen, Nicolas
Esser, Mark
Meuree, Ariane
Matys, Katie
Quint, Wim
van Doorn, Leen-Jan
Sherman, Mark E.
Herrero, Rolando
Pinto, Ligia A.
Hildesheim, Allan
TI Direct Comparison of HPV16 Serological Assays Used to Define HPV-Naive
Women in HPV Vaccine Trials
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID HUMAN-PAPILLOMAVIRUS; CERVICAL-CANCER; YOUNG-WOMEN; COSTA-RICA;
NEUTRALIZING EPITOPES; BROAD-SPECTRUM; ANTIBODIES; PCR;
HUMAN-PAPILLOMAVIRUS-18; SEROPREVALENCE
AB Background: Two HPV serological assays, the competitive Luminex immunoassay (cLIA), and an enzyme-linked immunoassay (ELISA) against HPV16 have been used to define HPV-naive subcohorts within large HPV vaccination trials. Some of the variation in estimated vaccine efficacies may be due to the differences in these assays used to define the HPV-naive subgroups. To guide the interpretation of published results, we compared these assays.
Methods: Replicate enrollment sera from a stratified sample of 388 unvaccinated women from the control arm of the Costa Rica HPV 16/18 Vaccine Trial were measured for antibodies against HPV16 using cLIA and ELISA. Agreement between the assays was estimated using standard and alternative assay cutoffs.
Results: Using laboratory-determined seropositivity cutoffs, sampling-adjusted HPV16 seropositivity was 24.8% by ELISA and 7.2% by cLIA. Comparing cLIA and ELISA antibody levels based on the standard cutoffs, overall agreement was 53% (positive-agreement = 49%). The poor agreement was mainly driven by the higher sensitivity of the ELISA than cLIA, resulting in 30% of the ELISA-positive sample that were cLIA-negative (none of the ELISA-negatives were cLIA-positive). Increasing ELISA cutoff to 54 ELISA units (EU)/mL (the level which maximized agreement with cLIA; ELISA standard cutoff is 8 EU/mL) resulted in higher agreement (overall agreement 91%; positive agreement = 78%).
Conclusions: ELISA and cLIA are different from each other based on the laboratory-determined cutoff. Increasing ELISA cutoff increased agreement with cLIA, which could facilitate comparisons among studies that use different assays.
Impact: Keeping cLIA at the laboratory-determined cutoff but altering ELISA cutoff for seropositivity might facilitate vaccine efficacy comparisons in the naive cohorts defined by cLIA. Cancer Epidemiol Biomarkers Prev; 21(9); 1547-54. (C) 2012 AACR.
C1 [Safaeian, Mahboobeh; Ghosh, Arpita; Lin, Shih-Wen; Schiffman, Mark; Wacholder, Sholom; Kemp, Troy; Wentzensen, Nicolas; Sherman, Mark E.; Pinto, Ligia A.; Hildesheim, Allan] NCI, NIH, Bethesda, MD 20892 USA.
[Quint, Wim; van Doorn, Leen-Jan] DDL Diagnost Lab, Voorburg, Netherlands.
[Meuree, Ariane] GlaxoSmithKline Biol, Rixensart, Belgium.
[Esser, Mark] MedImmune, Gaithersburg, MD USA.
[Matys, Katie] PPD Vaccines & Biol Ctr Excellence, Wayne, PA USA.
[Herrero, Rolando] Int Agcy Res Canc, Prevent & Implementat Grp, F-69372 Lyon, France.
RP Safaeian, M (reprint author), NCI, Div Canc Epidemiol & Genet, Infect & Immunoepidemiol Branch, 6120 Execut Blvd 7086, Rockville, MD 20852 USA.
EM safaeianm@mail.nih.gov
RI Hildesheim, Allan/B-9760-2015
OI Hildesheim, Allan/0000-0003-0257-2363
FU NCI; NIH Office of Research on Women's Health
FX Costa Rica HPV16/18 Vaccine Trial is funded by intramural NCI and the
NIH Office of Research on Women's Health and is conducted in agreement
with the Ministry of Health of Costa Rica.
NR 22
TC 11
Z9 11
U1 0
U2 2
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 2012
VL 21
IS 9
BP 1547
EP 1554
DI 10.1158/1055-9965.EPI-12-0558
PG 8
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 000NC
UT WOS:000308392000019
PM 22752082
ER
PT J
AU Lenz, P
Pfeiffer, R
Baris, D
Schned, AR
Takikita, M
Poscablo, MC
Schwenn, M
Johnson, A
Jones, M
Kida, M
Cantor, KP
Rothman, N
Silverman, DT
Hewitt, SM
Moore, LE
AF Lenz, Petra
Pfeiffer, Ruth
Baris, Dalsu
Schned, Alan R.
Takikita, Mikiko
Poscablo, M. Cristina
Schwenn, Molly
Johnson, Alison
Jones, Michael
Kida, Masatoshi
Cantor, Kenneth P.
Rothman, Nathaniel
Silverman, Debra T.
Hewitt, Stephen M.
Moore, Lee E.
TI Cell-Cycle Control in Urothelial Carcinoma: Large-scale Tissue Array
Analysis of Tumor Tissue from Maine and Vermont
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID P53 NUCLEAR OVEREXPRESSION; BLADDER-CANCER; PROGNOSTIC MARKERS; P63
EXPRESSION; E1 EXPRESSION; PROGRESSION; D1; CARCINOGENESIS;
IDENTIFICATION; PROLIFERATION
AB Background: Cell-cycle proteins are important predictive markers in urothelial carcinoma but may also exhibit exposure-specific heterogeneity.
Methods: Tumor tissue from 491 bladder cancer cases enrolled in the Maine and Vermont component of the New England Bladder Cancer Study was assembled as tissue microarrays and examined for aberrant expression of p53, p63, p16, cyclin D1, Rb, and Ki-67. The association between expression and histopathology, demographics, and cigarette smoking was examined using chi(2) tests, multivariable Poisson, and multinomial regression models.
Results: We found that overexpression of p53 and Ki-67 was associated with high-stage/grade tumors [relative risk (RR), 1.26; Ptrend 0.003; and RR, 3.21; P-trend < 0.0001, respectively], whereas expression of p63 and p16 was decreased in high-stage/grade tumors (RR, 0.52; P-trend < 0.0001; and RR, 0.88; P-trend = 0.04, respectively). No significant aberrations of cell-cycle proteins were identified using various smoking variables and multiple statistical models.
Conclusion: The results of this population-based study of histologically confirmed urothelial carcinomas show significant aberration of cell-cycle proteins p53, p63, p16, and Ki-67, but not Rb or cyclin D1. p53 showed the most significant heterogeneity with respect to tumor stage and grade, especially when stratified for different staining intensities using novel digital image analysis techniques. Our findings do not support that smoking modifies expression of cell-cycle proteins.
Impact: Our study shows significant heterogeneity in the expression of key cell-cycle proteins that are associated with disease progression in bladder cancer. Further studies may lead to the identification of biomarkers and their multiplexed interactions as useful prognostic and therapeutic targets. Cancer Epidemiol Biomarkers Prev; 21(9); 1555-64. (C) 2012 AACR.
C1 [Lenz, Petra] NCI, Div Canc Epidemiol & Genet, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21701 USA.
[Pfeiffer, Ruth; Baris, Dalsu; Poscablo, M. Cristina; Rothman, Nathaniel; Silverman, Debra T.; Moore, Lee E.] NCI, Epidemiol & Biostatist Program, NIH, Bethesda, MD 20892 USA.
[Takikita, Mikiko] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Schned, Alan R.; Hewitt, Stephen M.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Pathol, Hanover, NH 03756 USA.
[Schwenn, Molly] Maine Canc Registry, Augusta, ME USA.
[Johnson, Alison] Vermont Canc Registry, Burlington, VT USA.
[Jones, Michael] Maine Med Ctr, Dept Pathol & Lab Med, Portland, ME 04102 USA.
[Kida, Masatoshi] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA.
[Cantor, Kenneth P.] KP Cantor Environm LLC, Silver Spring, MD USA.
RP Moore, LE (reprint author), NCI, Occupat & Environm Epidemiol Branch, NIH, 6120 Execut Plaza S,Rm 8102, Rockville, MD 20852 USA.
EM moorele@mail.nih.gov
OI Hewitt, Stephen/0000-0001-8283-1788
FU National Cancer Institute, NIH [HHSN261200800001E]; NIH, Division of
Cancer Epidemiology and Genetics [N02-CP-01037]
FX This project has been funded, in whole or in part, with federal funds
from the National Cancer Institute, NIH, under Contract No.
HHSN261200800001E. Mention of trade names, commercial products, or
organizations does not imply endorsement by the U.S. Government. This
research was supported by the Intramural Research Program of the NIH,
Division of Cancer Epidemiology and Genetics (contract number
N02-CP-01037).
NR 33
TC 8
Z9 8
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 2012
VL 21
IS 9
BP 1555
EP 1564
DI 10.1158/1055-9965.EPI-12-0261
PG 10
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 000NC
UT WOS:000308392000020
PM 22761304
ER
PT J
AU Fuhrman, BJ
Brinton, LA
Pfeiffer, RM
Xu, X
Veenstra, TD
Teter, BE
Byrne, C
Dallal, CM
Barba, M
Muti, PC
Gierach, GL
AF Fuhrman, Barbara J.
Brinton, Louise A.
Pfeiffer, Ruth M.
Xu, Xia
Veenstra, Timothy D.
Teter, Barbara E.
Byrne, Celia
Dallal, Cher M.
Barba, Maddalena
Muti, Paola C.
Gierach, Gretchen L.
TI Estrogen Metabolism and Mammographic Density in Postmenopausal Women: A
Cross-Sectional Study
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID BREAST-CANCER RISK; TANDEM MASS-SPECTROMETRY; CIRCULATING SEX-HORMONES;
PARENCHYMAL PATTERNS; URINARY ESTROGENS; ASSOCIATION; STEROIDS;
REPRODUCIBILITY; CARCINOGENESIS; SUSCEPTIBILITY
AB Background: Prospective studies have consistently found that postmenopausal breast cancer risk increases with circulating estrogens; however, findings from studies of estrogens and mammographic density (MD), an intermediate marker of breast cancer risk, have been inconsistent. We investigated the cross-sectional associations of urinary estrogens, and their 2-, 4-, and 16-hydroxylated metabolites with MD.
Methods: Postmenopausal women without breast cancer (n = 194), ages 48 to 82 years, and reporting no current menopausal hormone therapy use were enrolled at a clinic in Western NY in 2005. Urinary estrogens and estrogen metabolites were measured using mass spectrometry. Percent MD and dense area (cm(2)) were measured using computer-assisted analyses of digitized films. Linear regression models were used to estimate associations of log-transformed estrogen measures with MD while adjusting for age, body mass index (BMI), parity, and past hormone therapy use.
Results: Urinary concentrations of most individual estrogens and metabolites were not associated with MD; however, across the interdecile range of the ratio of parent estrogens (estrone and estradiol) to their metabolites, MD increased by 6.8 percentage points (P = 0.02) and dense area increased by 10.3 cm(2) (P = 0.03). Across the interdecile ranges of the ratios of 2-, 4-, and 16-hydroxylation pathways to the parent estrogens, MD declined by 6.2 (P = 0.03), 6.4 (P = 0.04), and 5.7 (P = 0.05) percentage points, respectively. All associations remained apparent in models without adjustment for BMI.
Conclusion: In this study of postmenopausal women, less extensive hydroxylation of parent estrogens was associated with higher MD.
Impact: Hydroxylation of estrogens may modulate postmenopausal breast cancer risk through a pathway involving MD. Cancer Epidemiol Biomarkers Prev; 21(9); 1582-91. (C) 2012 AACR.
C1 [Fuhrman, Barbara J.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH,DHHS, Bethesda, MD 20892 USA.
[Pfeiffer, Ruth M.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA.
[Byrne, Celia] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA.
[Xu, Xia; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol Adv Technol Prpgram, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Teter, Barbara E.] SUNY Coll Buffalo, Buffalo, NY 14222 USA.
[Barba, Maddalena; Muti, Paola C.] McMaster Univ, Juravinski Canc Ctr, Hamilton, ON, Canada.
RP Fuhrman, BJ (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH,DHHS, 6120 Execut Blvd MSC 7234, Bethesda, MD 20892 USA.
EM fuhrmanb@mail.nih.gov
RI Brinton, Louise/G-7486-2015; Gierach, Gretchen/E-1817-2016; Byrne,
Celia/K-2964-2015;
OI Brinton, Louise/0000-0003-3853-8562; Gierach,
Gretchen/0000-0002-0165-5522; Byrne, Celia/0000-0001-8289-4252; Fuhrman,
Barbara/0000-0002-1777-9888
FU Division of Cancer Epidemiology and Genetics of the National Cancer
Institute (NCI), NIH; NCI, NIH, DHHS [HHSN261200800001E]
FX This work was supported by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics of the National Cancer
Institute (NCI), NIH and contract #HHSN261200800001E to SAIC, Inc. from
NCI, NIH, DHHS. The views expressed are those of the authors and do not
reflect the official policy or position of the USUHS, the Department of
Defense, or the United States Government.
NR 42
TC 9
Z9 9
U1 0
U2 2
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 2012
VL 21
IS 9
BP 1582
EP 1591
DI 10.1158/1055-9965.EPI-12-0247
PG 10
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 000NC
UT WOS:000308392000023
PM 22736791
ER
PT J
AU Mondul, AM
Weinstein, SJ
Albanes, D
AF Mondul, Alison M.
Weinstein, Stephanie J.
Albanes, Demetrius
TI Serum Vitamin D and Risk of Bladder Cancer in PLCO-Response
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Letter
C1 [Mondul, Alison M.; Weinstein, Stephanie J.; Albanes, Demetrius] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
RP Mondul, AM (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd, Rockville, MD 20852 USA.
EM mondulam@mail.nih.gov
RI Albanes, Demetrius/B-9749-2015
NR 5
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD SEP
PY 2012
VL 21
IS 9
BP 1603
EP 1603
DI 10.1158/1055-9965.EPI-12-0811
PG 1
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 000NC
UT WOS:000308392000027
ER
PT J
AU Ozato, K
AF Ozato, K.
TI Chromatin exchange in interferon induced transcription
SO CYTOKINE
LA English
DT Meeting Abstract
CT 10th Joint Meeting of the International-Cytokine-Society (ICS) / Meeting
of the International-Society-for-Interferon-and-Cytokine-Research
(ISICR)
CY SEP 11-14, 2012
CL Geneva, SWITZERLAND
SP Int Cytokine Soc (ICS), Int Soc Interferon & Cytokine Res (ISICR)
C1 [Ozato, K.] NICHD, PGD, NIH, Bethesda, MD 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 2012
VL 59
IS 3
SI SI
BP 494
EP 494
DI 10.1016/j.cyto.2012.06.307
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 005FG
UT WOS:000308735300022
ER
PT J
AU Durum, S
Li, W
Zenatti, P
Ribeiro, D
Zuurbier, L
Silva, M
Paganin, M
Tritapoe, J
Hixon, J
Silveira, A
Cardoso, B
Sarmento, L
Correia, N
Toribio, M
Kobarg, J
Horstmann, M
Pieters, R
Brandalise, S
Ferrando, A
Meijerink, J
Yunes, J
Barata, J
AF Durum, S.
Li, W.
Zenatti, P.
Ribeiro, D.
Zuurbier, L.
Silva, M.
Paganin, M.
Tritapoe, J.
Hixon, J.
Silveira, A.
Cardoso, B.
Sarmento, L.
Correia, N.
Toribio, M.
Kobarg, J.
Horstmann, M.
Pieters, R.
Brandalise, S.
Ferrando, A.
Meijerink, J.
Yunes, J.
Barata, J.
TI Oncogenic IL-7R gain-of-function mutations in childhood T-ALL
SO CYTOKINE
LA English
DT Meeting Abstract
CT 10th Joint Meeting of the International-Cytokine-Society (ICS) / Meeting
of the International-Society-for-Interferon-and-Cytokine-Research
(ISICR)
CY SEP 11-14, 2012
CL Geneva, SWITZERLAND
SP Int Cytokine Soc (ICS), Int Soc Interferon & Cytokine Res (ISICR)
C1 [Durum, S.; Li, W.] NCI, NIH, Frederick, MD 21701 USA.
[Zenatti, P.; Silveira, A.; Brandalise, S.; Yunes, J.] Ctr Infantil Boldrin, Campinas, SP, Brazil.
[Ribeiro, D.; Silva, M.; Cardoso, B.; Sarmento, L.; Correia, N.; Barata, J.] Univ Lisbon, P-1699 Lisbon, Portugal.
[Zuurbier, L.; Pieters, R.; Meijerink, J.] Erasmus MC, Rotterdam, Netherlands.
[Paganin, M.; Ferrando, A.] Columbia Univ, New York, NY USA.
[Toribio, M.] Univ Autonoma Madrid, Madrid, Spain.
[Kobarg, J.] Ctr Nacl Pesquisa, Campinas, SP, Brazil.
[Horstmann, M.] Univ Med Ctr Hamburg, Hamburg, Germany.
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 2012
VL 59
IS 3
SI SI
BP 507
EP 507
DI 10.1016/j.cyto.2012.06.055
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 005FG
UT WOS:000308735300053
ER
PT J
AU Ozato, K
Sarai, N
Patel, M
Debrosse, M
Heightman, T
Tamura, T
Ura, K
AF Ozato, K.
Sarai, N.
Patel, M.
Debrosse, M.
Heightman, T.
Tamura, T.
Ura, K.
TI Chromatin exchange in interferon induced transcription
SO CYTOKINE
LA English
DT Meeting Abstract
CT 10th Joint Meeting of the International-Cytokine-Society (ICS) / Meeting
of the International-Society-for-Interferon-and-Cytokine-Research
(ISICR)
CY SEP 11-14, 2012
CL Geneva, SWITZERLAND
SP Int Cytokine Soc (ICS), Int Soc Interferon & Cytokine Res (ISICR)
C1 [Ozato, K.; Sarai, N.; Patel, M.; Debrosse, M.] NICHD, PGD, NIH, Bethesda, MD USA.
[Heightman, T.] Astex Pharmaceut, Cambridge, England.
[Tamura, T.] Yokohama City Univ, Sch Med, Yokohama, Kanagawa 232, Japan.
[Ura, K.] Osaka Univ, Sch Med, Osaka, Japan.
RI Patel, Mira/A-3013-2015
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 2012
VL 59
IS 3
SI SI
BP 511
EP 511
DI 10.1016/j.cyto.2012.06.063
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 005FG
UT WOS:000308735300059
ER
PT J
AU Alemu, BS
Famanta, A
Doumbia, S
Samake, S
Traore, B
Duan, J
Zaidi, I
Fairhurst, RM
Long, CA
Duffy, PE
Diakite, M
Walther, M
AF Alemu, B. Seyoum
Famanta, A.
Doumbia, S.
Samake, S.
Traore, B.
Duan, J.
Zaidi, I.
Fairhurst, R. M.
Long, C. A.
Duffy, P. E.
Diakite, M.
Walther, M.
TI Cellular responses to repeated malaria episodes: Does the concept of
original antigenic sin apply to Plasmodium falciparum malaria?
SO CYTOKINE
LA English
DT Meeting Abstract
CT 10th Joint Meeting of the International-Cytokine-Society (ICS) / Meeting
of the International-Society-for-Interferon-and-Cytokine-Research
(ISICR)
CY SEP 11-14, 2012
CL Geneva, SWITZERLAND
SP Int Cytokine Soc (ICS), Int Soc Interferon & Cytokine Res (ISICR)
C1 [Alemu, B. Seyoum; Duan, J.; Zaidi, I.; Duffy, P. E.; Walther, M.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD USA.
[Famanta, A.; Doumbia, S.; Samake, S.; Traore, B.; Diakite, M.] Univ Bamako, Malaria Res & Training Ctr, Bamako, Mali.
[Fairhurst, R. M.; Long, C. A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 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 2012
VL 59
IS 3
SI SI
BP 520
EP 520
DI 10.1016/j.cyto.2012.06.088
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 005FG
UT WOS:000308735300079
ER
PT J
AU Thomas, E
Liang, TJ
AF Thomas, E.
Liang, T. J.
TI HCV infection induces a unique hepatic innate immune response associated
with robust production of type III interferons
SO CYTOKINE
LA English
DT Meeting Abstract
CT 10th Joint Meeting of the International-Cytokine-Society (ICS) / Meeting
of the International-Society-for-Interferon-and-Cytokine-Research
(ISICR)
CY SEP 11-14, 2012
CL Geneva, SWITZERLAND
SP Int Cytokine Soc (ICS), Int Soc Interferon & Cytokine Res (ISICR)
C1 [Thomas, E.] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr & Cell Biol, Miami, FL 33136 USA.
[Liang, T. J.] NIDDK, Liver Dis Branch, 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 2012
VL 59
IS 3
SI SI
BP 521
EP 521
DI 10.1016/j.cyto.2012.06.091
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 005FG
UT WOS:000308735300082
ER
PT J
AU Olejnik, J
Marzi, A
Feldmann, H
Muhlberger, E
AF Olejnik, J.
Marzi, A.
Feldmann, H.
Muehlberger, E.
TI Ebola virus induces a differential cytokine response and NFKB activation
in infected cells
SO CYTOKINE
LA English
DT Meeting Abstract
CT 10th Joint Meeting of the International-Cytokine-Society (ICS) / Meeting
of the International-Society-for-Interferon-and-Cytokine-Research
(ISICR)
CY SEP 11-14, 2012
CL Geneva, SWITZERLAND
SP Int Cytokine Soc (ICS), Int Soc Interferon & Cytokine Res (ISICR)
C1 [Olejnik, J.; Marzi, A.; Muehlberger, E.] Boston Univ, Natl Emerging Dis Labs, Boston, MA 02215 USA.
[Feldmann, H.] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA.
NR 0
TC 0
Z9 0
U1 2
U2 10
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 2012
VL 59
IS 3
SI SI
BP 523
EP 523
DI 10.1016/j.cyto.2012.06.097
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 005FG
UT WOS:000308735300088
ER
PT J
AU Kumar, R
Gautam, S
Singh, OP
Singh, N
Nylen, S
Sacks, D
Sundar, S
AF Kumar, R.
Gautam, S.
Singh, O. P.
Singh, N.
Nylen, S.
Sacks, D.
Sundar, S.
TI CD4+T cells are source of antigen specific interferon-gamma production
in whole blood of patients with visceral leishmaniasis
SO CYTOKINE
LA English
DT Meeting Abstract
CT 10th Joint Meeting of the International-Cytokine-Society (ICS) / Meeting
of the International-Society-for-Interferon-and-Cytokine-Research
(ISICR)
CY SEP 11-14, 2012
CL Geneva, SWITZERLAND
SP Int Cytokine Soc (ICS), Int Soc Interferon & Cytokine Res (ISICR)
C1 [Kumar, R.; Gautam, S.; Singh, O. P.; Singh, N.; Sundar, S.] Banaras Hindu Univ India, Varanasi, Uttar Pradesh, India.
[Nylen, S.] Karolinska Inst, Stockhome, Sweden.
[Sacks, D.] NIAID, Parasit Dis Lab, NIH, 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 2012
VL 59
IS 3
SI SI
BP 527
EP 527
DI 10.1016/j.cyto.2012.06.111
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 005FG
UT WOS:000308735300102
ER
PT J
AU Hanson, E
Zilberman-Rudenko, J
Cheng, L
Ashwell, J
Siegel, RM
Orange, JS
AF Hanson, E.
Zilberman-Rudenko, J.
Cheng, L.
Ashwell, J.
Siegel, R. M.
Orange, J. S.
TI Skewed binding of linear ubiquitin chains underlies inflammatory
pathology in NEMO syndrome
SO CYTOKINE
LA English
DT Meeting Abstract
CT 10th Joint Meeting of the International-Cytokine-Society (ICS) / Meeting
of the International-Society-for-Interferon-and-Cytokine-Research
(ISICR)
CY SEP 11-14, 2012
CL Geneva, SWITZERLAND
SP Int Cytokine Soc (ICS), Int Soc Interferon & Cytokine Res (ISICR)
C1 [Hanson, E.; Zilberman-Rudenko, J.] NIAMS, Autoimmun Branch, NIH, Bethesda, MD USA.
[Cheng, L.] UCSF, San Francisco, CA USA.
[Ashwell, J.] NCI, NIH, Bethesda, MD 20892 USA.
[Orange, J. S.] Baylor Univ, Houston, TX 77030 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 2012
VL 59
IS 3
SI SI
BP 546
EP 547
DI 10.1016/j.cyto.2012.06.173
PG 2
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 005FG
UT WOS:000308735300157
ER
PT J
AU Lundstrom, W
Walsh, S
Beq, S
Hillert, J
Mackall, C
AF Lundstrom, W.
Walsh, S.
Beq, S.
Hillert, J.
Mackall, C.
TI Soluble IL7Ra isoform modulates IL7 signalling and homeostasis
SO CYTOKINE
LA English
DT Meeting Abstract
CT 10th Joint Meeting of the International-Cytokine-Society (ICS) / Meeting
of the International-Society-for-Interferon-and-Cytokine-Research
(ISICR)
CY SEP 11-14, 2012
CL Geneva, SWITZERLAND
SP Int Cytokine Soc (ICS), Int Soc Interferon & Cytokine Res (ISICR)
C1 [Lundstrom, W.; Hillert, J.] Karolinska Inst, Stockholm, Sweden.
[Lundstrom, W.; Mackall, C.] NCI, Bethesda, MD 20892 USA.
[Walsh, S.] Univ Maryland, College Pk, MD 20742 USA.
[Beq, S.] Cytheris SA, Issy Le Moulineaux, France.
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 2012
VL 59
IS 3
SI SI
BP 551
EP 551
DI 10.1016/j.cyto.2012.06.188
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 005FG
UT WOS:000308735300172
ER
PT J
AU Morrow, AN
Zoon, KC
AF Morrow, A. N.
Zoon, K. C.
TI Novel unphosphorylated SIAT-containing transcription factor complex
formation induced by IFN-gamma treatment results in antiviral activity
SO CYTOKINE
LA English
DT Meeting Abstract
CT 10th Joint Meeting of the International-Cytokine-Society (ICS) / Meeting
of the International-Society-for-Interferon-and-Cytokine-Research
(ISICR)
CY SEP 11-14, 2012
CL Geneva, SWITZERLAND
SP Int Cytokine Soc (ICS), Int Soc Interferon & Cytokine Res (ISICR)
C1 [Morrow, A. N.; Zoon, K. C.] NIAID, CBS, NIH, Bethesda, MD 20892 USA.
[Morrow, A. N.] Georgetown Univ, Dept Microbiol & Immunol, Washington, DC 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 2012
VL 59
IS 3
SI SI
BP 553
EP 553
DI 10.1016/j.cyto.2012.06.195
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 005FG
UT WOS:000308735300176
ER
PT J
AU Azimi, N
Massoud, R
Jacobson, S
Tagaya, Y
AF Azimi, N.
Massoud, R.
Jacobson, S.
Tagaya, Y.
TI Selective inhibition of multiple cytokines: A novel therapeutic strategy
for immune-mediated diseases
SO CYTOKINE
LA English
DT Meeting Abstract
CT 10th Joint Meeting of the International-Cytokine-Society (ICS) / Meeting
of the International-Society-for-Interferon-and-Cytokine-Research
(ISICR)
CY SEP 11-14, 2012
CL Geneva, SWITZERLAND
SP Int Cytokine Soc (ICS), Int Soc Interferon & Cytokine Res (ISICR)
C1 [Azimi, N.] Bioniz, Lake Forest, IL USA.
[Massoud, R.; Jacobson, S.] NIH, Bethesda, MD 20892 USA.
[Tagaya, Y.] Inst Human Virol, Baltimore, 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 2012
VL 59
IS 3
SI SI
BP 573
EP 573
DI 10.1016/j.cyto.2012.06.269
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 005FG
UT WOS:000308735300237
ER
PT J
AU Laiyemo, AO
Doubeni, C
Badurdeen, DS
Murphy, G
Marcus, PM
Schoen, RE
Lanza, E
Smoot, DT
Cross, AJ
AF Laiyemo, A. O.
Doubeni, C.
Badurdeen, D. S.
Murphy, G.
Marcus, P. M.
Schoen, R. E.
Lanza, E.
Smoot, D. T.
Cross, A. J.
TI Obesity, weight change, and risk of adenoma recurrence: a prospective
trial
SO ENDOSCOPY
LA English
DT Article
ID BODY-MASS INDEX; COLORECTAL ADENOMA; PHYSICAL-ACTIVITY; COLON-CANCER;
UNITED-STATES; METAANALYSIS; COHORT; OVERWEIGHT; ADULTS; SIZE
AB Background and study aims: Obesity is a risk factor for colorectal neoplasia. Lifestyle modifications, including weight loss, have been advocated to reduce the risk. However, no prospective study has evaluated whether weight loss actually affects adenoma recurrence. The aim of this study was to examine whether weight change (loss or gain) over 4 years is associated with adenoma recurrence.
Patients and methods: A total of 1826 patients with colorectal adenoma in the Polyp Prevention Trial had their height and weight measured at baseline. Adenoma recurrence was determined by end of trial colonoscopy 4 years after study entry when patients' weights were re-measured. Poisson regression models were used to evaluate body mass index (BMI), weight change over 4 years, and the risk of any adenoma and advanced adenoma recurrence.
Results: Adenoma recurrence was observed in 723 patients (39.6 %), 118 (6.5 %) of whom had advanced adenoma recurrence. Among those with baseline BMI <25kg/m(2) (n = 466), BMI 25-29kg/m(2) (n = 868), and BMI = 30kg/m(2) (n = 492), the recurrence rate was 34.5 %, 41.0 %, and 41.9 %, respectively. Obesity was associated with an increased risk of adenoma recurrence (RR = 1.19; 95%CI 1.01-1.39) and advanced adenoma recurrence (RR = 1.62; 95%CI 1.01-2.57). However, when compared with those with relatively stable weight (weight change <5 lb) over the 4-year trial, weight gain or loss was not associated with adenoma recurrence. This was consistent, regardless of the baseline BMI.
Conclusions: Weight loss or gain over 4 years does not affect adenoma recurrence. This study does not support weight loss alone as an effective intervention for reducing adenoma recurrence.
C1 [Laiyemo, A. O.; Badurdeen, D. S.; Smoot, D. T.] Howard Univ, Coll Med, Dept Med, Div Gastroenterol, Washington, DC 20060 USA.
[Laiyemo, A. O.; Marcus, P. M.] NCI, Biometry Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Doubeni, C.] Univ Massachusetts, Dept Family Med, Worcester, MA 01605 USA.
[Murphy, G.; Cross, A. J.] NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Schoen, R. E.] Univ Pittsburgh, Dept Med & Epidemiol, Pittsburgh, PA USA.
[Lanza, E.] NCI, Lab Canc Prevent, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NCI, Bethesda, MD 20892 USA.
RP Laiyemo, AO (reprint author), Howard Univ, Coll Med, Dept Med, Div Gastroenterol, 2041 Georgia Ave NW, Washington, DC 20060 USA.
EM adeyinka.laiyemo@howard.edu
OI Doubeni, Chyke/0000-0001-7495-0285
FU National Cancer Institute; Howard University Cancer Center; Sidney
Kimmel Comprehensive Cancer Center of Johns Hopkins University
[5U54CA091431-09 S1]; National Cancer Institute [5K01CA127118-03];
Intramural Research Program of the Division of Cancer Epidemiology and
Genetics; Division of Cancer Prevention at the National Cancer
Institute, National Institutes of Health
FX Dr. Laiyemo is supported by the National Cancer Institute's new faculty
recruitment supplement to the Comprehensive Minority Institution/Cancer
Center Partnership between Howard University Cancer Center and Sidney
Kimmel Comprehensive Cancer Center of Johns Hopkins University
(5U54CA091431-09 S1). Dr. Doubeni is supported by a mentored career
development award (5K01CA127118-03) from the National Cancer Institute.
The study was funded by Intramural Research Program of the Division of
Cancer Epidemiology and Genetics and the Division of Cancer Prevention
at the National Cancer Institute, National Institutes of Health.
NR 26
TC 18
Z9 18
U1 0
U2 7
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0013-726X
J9 ENDOSCOPY
JI Endoscopy
PD SEP
PY 2012
VL 44
IS 9
BP 813
EP 818
DI 10.1055/s-0032-1309837
PG 6
WC Gastroenterology & Hepatology; Surgery
SC Gastroenterology & Hepatology; Surgery
GA 000GE
UT WOS:000308373700002
PM 22926666
ER
PT J
AU Zhang, Y
Sun, K
Yu, L
Tang, ZR
Huang, SB
Meng, ZH
Zheng, YJ
Wen, Y
Zhu, H
Chen, RY
Varma, JK
Zhang, FJ
AF Zhang, Yao
Sun, Kai
Yu, Lan
Tang, Zhirong
Huang, Shaobiao
Meng, Zhihao
Zheng, Yuanjia
Wen, Yi
Zhu, Hao
Chen, Ray Y.
Varma, Jay K.
Zhang, Fujie
TI Factors associated with survival among adults with HIV-associated TB in
Guangxi, China: a retrospective cohort study
SO FUTURE VIROLOGY
LA English
DT Article
DE HAART; HIV; survival; tuberculosis
ID ACTIVE ANTIRETROVIRAL THERAPY; DRUG-RESISTANT TUBERCULOSIS; INFECTED
PATIENTS; PULMONARY TUBERCULOSIS; COTRIMOXAZOLE PROPHYLAXIS;
RISK-FACTORS; MORTALITY; DIAGNOSIS; THAILAND; COINFECTION
AB Aim: Although China has the second highest burden of TB in the world and faces a burgeoning HIV epidemic, the epidemiology and 12-month clinical outcomes of HIV-infected TB patients have not previously been reported. Methods: We reviewed records of all HIV-infected adults diagnosed with culture-confirmed TB from four HIV clinics in Guangxi, China from August 2006 to December 2008. Factors associated with patients' survival within 12 months after TB diagnosis were evaluated in Cox proportional hazards models. Results: Among the 201 patients included, 47 (23%) died within 12 months. Median CD4 count at TB diagnosis was 37 cells/mm(3) (interquartile range: 16-102). Receiving HAART (adjusted hazard ratio (AHR): 4.2; 95% CI: 1.6-10.8), receiving TB treatment (AHR: 9.0; 95% CI: 1.5-53.5) and baseline BMI >= 18.5 (AHR: 8.4; 95% CI: 1.9-35.8) were independently associated with survival. Among 171 (85%) patients who received TB treatment, receiving HAART (HR: 5.1; 95% CI: 2.4-10.7) was the only factor significantly associated with survival. Conclusion: HIV-infected Chinese patients diagnosed with TB in Guangxi are at high risk of death within 12 months, a risk that is strongly mitigated by antiretroviral therapy. Improving survival from HIV-associated TB in China will require the integration of TB and HIV programs to improve access to treatment for both diseases.
C1 [Zhang, Yao; Yu, Lan; Wen, Yi; Zhang, Fujie] Chinese Ctr Dis Control & Prevent, Natl Ctr AIDS STD Control & Prevent, Beijing, Peoples R China.
[Sun, Kai; Zhu, Hao] Univ N Carolina, Chapel Hill, NC USA.
[Tang, Zhirong] Prov Ctr Dis Control & Prevent Guangxi, Nanning, Peoples R China.
[Huang, Shaobiao] Nanning 4th Peoples Hosp, Nanning, Peoples R China.
[Meng, Zhihao] Liuzhou Longtan Hosp, Liuzhou, Peoples R China.
[Zheng, Yuanjia] Ctr Dis Control & Prevent Liuzhou City, Liuzhou, Peoples R China.
[Chen, Ray Y.] NIAID, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Varma, Jay K.] US Ctr Dis Control & Prevent, Atlanta, GA USA.
[Zhang, Fujie] Capital Med Univ, Beijing Ditan Hosp, Beijing, Peoples R China.
RP Zhang, FJ (reprint author), Chinese Ctr Dis Control & Prevent, Natl Ctr AIDS STD Control & Prevent, Beijing, Peoples R China.
EM zhang.fujie.t@gmail.com
OI Chen, Ray/0000-0001-6344-1442
FU China Ministry of Science and Technology Chinese National Basic Research
Program [973:2006CB504201]
FX This study was supported in part by the China Ministry of Science and
Technology Chinese National Basic Research Program (973:2006CB504201).
The authors have no other relevant affiliations or financial involvement
with any organization or entity with a financial interest in or
financial conflict with the subject matter or materials discussed in the
manuscript apart from those disclosed.
NR 43
TC 2
Z9 2
U1 1
U2 4
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1746-0794
J9 FUTURE VIROL
JI Future Virol.
PD SEP
PY 2012
VL 7
IS 9
BP 933
EP 942
DI 10.2217/FVL.12.76
PG 10
WC Virology
SC Virology
GA 001GU
UT WOS:000308449400013
ER
PT J
AU Feuermann, Y
Robinson, GW
Zhu, BM
Kang, K
Raviv, N
Yamaji, D
Hennighausen, L
AF Feuermann, Yonatan
Robinson, Gertraud W.
Zhu, Bing-Mei
Kang, Keunsoo
Raviv, Noa
Yamaji, Daisuke
Hennighausen, Lothar
TI The miR-17/92 cluster is targeted by STAT5 but dispensable for mammary
development
SO GENESIS
LA English
DT Article
DE STAT5; miR-17; 92 cluster; mammary gland
ID TGF-BETA; GLAND DEVELOPMENT; MICRORNA EXPRESSION; PROGENITOR CELLS;
GENE; DIFFERENTIATION; PROLIFERATION; EPITHELIUM; PREGNANCY; DELETION
AB Genome wide analysis revealed the miR-17/92 cluster as a STAT5 target. This cluster encodes six microRNAs, which predictably target genes that play a role in mammary gland development. In this study, we have deleted the miR-17/92 cluster in mammary stem cells and evaluated in the mouse its function during mammary gland development. Loss of the miR-17/92 cluster did not affect mammary development from prepuberty to lactation. Our studies demonstrated that, while expression of the miR-17/92 cluster is under control of the key mammary transcription factor STAT5, its presence is not required for normal mammary development or lactation. genesis 50:665671, 2012. (c) 2012 Wiley Periodicals, Inc.
C1 [Feuermann, Yonatan; Robinson, Gertraud W.; Kang, Keunsoo; Raviv, Noa; Yamaji, Daisuke; Hennighausen, Lothar] NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA.
[Zhu, Bing-Mei] Nanjing Univ Chinese Med, Minister Educ, Key Lab Acupuncture & Med Res, Nanjing 210029, Jiangsu, Peoples R China.
[Hennighausen, Lothar] Dankook Univ, Dept Nanobiomed Sci, Chungnam 330714, South Korea.
[Hennighausen, Lothar] Dankook Univ, WCU Res Ctr Nanobiomed Sci, Chungnam 330714, South Korea.
RP Feuermann, Y (reprint author), NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA.
EM feuermanny@mail.nih.gov
RI Robinson, Gertraud/I-2136-2012;
OI Feuermann, Yonatan/0000-0002-6561-6397
FU National Institute of Diabetes and Digestive and Kidney Diseases, NIH
FX Contract grant sponsor: Intramural Research Program of the National
Institute of Diabetes and Digestive and Kidney Diseases, NIH.
NR 27
TC 13
Z9 14
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1526-954X
J9 GENESIS
JI Genesis
PD SEP
PY 2012
VL 50
IS 9
BP 665
EP 671
DI 10.1002/dvg.22023
PG 7
WC Developmental Biology; Genetics & Heredity
SC Developmental Biology; Genetics & Heredity
GA 009YT
UT WOS:000309062200002
PM 22389215
ER
PT J
AU Zuurbier, L
Petricoin, EF
Vuerhard, MJ
Calvert, V
Kooi, C
Buijs-Gladdines, JGCAM
Smits, WK
Sonneveld, E
Veerman, AJP
Kamps, WA
Horstmann, M
Pieters, R
Meijerink, JPP
AF Zuurbier, Linda
Petricoin, Emanuel F., III
Vuerhard, Maartje J.
Calvert, Valerie
Kooi, Clarissa
Buijs-Gladdines, Jessica G. C. A. M.
Smits, Willem K.
Sonneveld, Edwin
Veerman, Anjo J. P.
Kamps, Willem A.
Horstmann, Martin
Pieters, Rob
Meijerink, Jules P. P.
TI The significance of PTEN and AKT aberrations in pediatric T-cell acute
lymphoblastic leukemia
SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
LA English
DT Article
DE pediatric T-ALL; PTEN; AKT; NOTCH1; gamma-secretase resistance; outcome
ID SPORADIC BREAST-CANCER; NOTCH1 MUTATIONS; PROGNOSTIC-SIGNIFICANCE;
ACTIVATION MECHANISM; FBXW7 MUTATIONS; GENE-EXPRESSION; COWDEN-SYNDROME;
CHILDREN; PROTOCOL; IMPACT
AB Background
PI3K/AKT pathway mutations are found in T-cell acute lymphoblastic leukemia, but their overall impact and associations with other genetic aberrations is unknown. PTEN mutations have been proposed as secondary mutations that follow NOTCH1-activating mutations and cause cellular resistance to gamma-secretase inhibitors.
Design and Methods
The impact of PTEN, PI3K and AKT aberrations was studied in a genetically well-characterized pediatric T-cell leukemia patient cohort (n=146) treated on DCOG or COALL protocols.
Results
PTEN and AKT E17K aberrations were detected in 13% and 2% of patients, respectively. Defective PTEN-splicing was identified in incidental cases. Patients without PTEN protein but lacking exon-, splice-, promoter mutations or promoter hypermethylation were present. PTEN/AKT mutations were especially abundant in TAL- or LMO-rearranged leukemia but nearly absent in TLX3-rearranged patients (P=0.03), the opposite to that observed for NOTCH1-activating mutations. Most PTEN/AKT mutant patients either lacked NOTCH1-activating mutations (P=0.006) or had weak NOTCH1-activating mutations (P=0.011), and consequently expressed low intracellular NOTCH1, cMYC and MUSASHI levels. T-cell leukemia patients without PTEN/AKT and NOTCH1-activating mutations fared well, with a cumulative incidence of relapse of only 8% versus 35% for PTEN/AKT and/or NOTCH1-activated patients (P=0.005).
Conclusions
PI3K/AKT pathway aberrations are present in 18% of pediatric T-cell acute lymphoblastic leukemia patients. Absence of strong NOTCH1-activating mutations in these cases may explain cellular insensitivity to gamma-secretase inhibitors.
C1 [Zuurbier, Linda; Vuerhard, Maartje J.; Kooi, Clarissa; Buijs-Gladdines, Jessica G. C. A. M.; Smits, Willem K.; Pieters, Rob; Meijerink, Jules P. P.] Sophia Childrens Univ Hosp, Erasmus MC, Dept Pediat Oncol Hematol, NL-3015 GJ Rotterdam, Netherlands.
[Petricoin, Emanuel F., III; Calvert, Valerie] George Mason Univ, Ctr Appl Prote & Mol Med, Manassas, VA USA.
[Petricoin, Emanuel F., III] NCI, FDA Clin Prote Program, US FDA, Bethesda, MD 20892 USA.
[Veerman, Anjo J. P.; Kamps, Willem A.] DCOG, The Hague, Netherlands.
[Veerman, Anjo J. P.] Vrije Univ Amsterdam Med Ctr, Dept Pediat Oncol Hematol, Amsterdam, Netherlands.
[Smits, Willem K.] Univ Groningen, Univ Med Ctr Groningen, Beatrix Childrens Hosp, Dept Pediat Oncol, Groningen, Netherlands.
[Horstmann, Martin] German Cooperat Study Grp Childhood Acute Lymphob, Hamburg, Germany.
[Horstmann, Martin] Univ Med Ctr Hamburg Eppendorf, Clin Pediat Hematol & Oncol, Childrens Canc Ctr Hamburg, Inst Res, Hamburg, Germany.
RP Meijerink, JPP (reprint author), Sophia Childrens Univ Hosp, Erasmus MC, Dept Pediat Oncol Hematol, Room Sp2456,Dr Molewaterpl 60, NL-3015 GJ Rotterdam, Netherlands.
EM j.meijerink@erasmusmc.nl
RI Meijerink, Jules/D-4393-2017
OI Meijerink, Jules/0000-0002-6860-798X
FU Children Cancer Free Foundation (Stichting Kinderen Kankervrij (KiKa));
Erasmus University Trustfonds foundation; Children Cancer Free
Foundation [KIKA2007-012, KIKA2008-029, AMC2008-4265]
FX this work was supported by the Children Cancer Free Foundation
(Stichting Kinderen Kankervrij (KiKa)) and the Erasmus University
Trustfonds foundation. The Children Cancer Free Foundation grants
KIKA2007-012 (L.Z. and C.K.), KIKA2008-029 (W.K.S.) and AMC2008-4265
(J.B.-G.).
NR 48
TC 35
Z9 38
U1 1
U2 7
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOL-HEMATOL J
JI Haematol-Hematol. J.
PD SEP
PY 2012
VL 97
IS 9
BP 1405
EP 1413
DI 10.3324/haematol.2011.059030
PG 9
WC Hematology
SC Hematology
GA 007SL
UT WOS:000308908300021
PM 22491738
ER
PT J
AU Slotta-Huspenina, J
Koch, I
de Leval, L
Keller, G
Klier, M
Bink, K
Kremer, M
Raffeld, M
Fend, F
Quintanilla-Martinez, L
AF Slotta-Huspenina, Julia
Koch, Ina
de Leval, Laurence
Keller, Gisela
Klier, Margit
Bink, Karin
Kremer, Marcus
Raffeld, Mark
Fend, Falko
Quintanilla-Martinez, Leticia
TI The impact of cyclin D1 mRNA isoforms, morphology and p53 in mantle cell
lymphoma: p53 alterations and blastoid morphology are strong predictors
of a high proliferation index
SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
LA English
DT Article
DE cyclin D1 mRNA; isoforms; mantle cell lymphoma; prognosis
ID EUROPEAN-MCL-NETWORK; MULTIPLE-MYELOMA; ALTERNATIVE TRANSCRIPTS;
AGGRESSIVE VARIANTS; GENOMIC DELETIONS; RELATIVE LEVELS; POOR-PROGNOSIS;
GENE; EXPRESSION; OVEREXPRESSION
AB Background
Mantle cell lymphoma is a clinically heterogeneous disease characterized by overexpression of cyclin D1 protein. Blastoid morphology, high proliferation, and secondary genetic aberrations are markers of aggressive behavior. Expression profiling of mantle cell lymphoma revealed that predominance of the 3'UTR-deficient, short cyclin D1 mRNA isoform was associated with high cyclin D1 levels, a high "proliferation signature" and poor prognosis.
Design and Methods
Sixty-two cases of mantle cell lymphoma were analyzed for cyclin D1 mRNA isoforms and total cyclin D1 levels by real-time reverse transcriptase polymerase chain reaction, and TP53 alterations were assessed by immunohistochemistry and molecular analysis. Results were correlated with proliferation index and clinical outcome.
Results
Predominance of the short cyclin D1 mRNA was found in 14 (23%) samples, including four with complete loss of the standard transcript. TP53 alterations were found in 15 (24%) cases. Predominance of 3'UTR-deficient mRNA was significantly associated with high cyclin D1 mRNA levels (P=0.009) and more commonly found in blastoid mantle cell lymphoma (5/11, P=0.060) and cases with a proliferation index of >20% (P=0.026). Both blastoid morphology (11/11, P<0.001) and TP53 alterations (15/15, P<0.001) were significantly correlated with a high proliferation index. A proliferation index of 10% was determined to be a significant threshold for survival in multivariate analysis (P=0.01).
Conclusions
TP53 alterations are strongly associated with a high proliferation index and aggressive behavior in mantle cell lymphoma. Predominance of the 3'UTR-deficient transcript correlates with higher cyclin D1 levels and may be a secondary contributing factor to high proliferation, but failed to reach prognostic significance in this study.
C1 [Slotta-Huspenina, Julia; Koch, Ina; Keller, Gisela; Klier, Margit; Kremer, Marcus] Tech Univ Munich, Inst Pathol, Munich, Germany.
[de Leval, Laurence] Univ Liege, CHU Sart Tilman, Dept Pathol, Liege, Belgium.
[Bink, Karin] Helmholtz Ctr Munich, Inst Pathol, Neuherberg, Germany.
[Raffeld, Mark] NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Fend, Falko; Quintanilla-Martinez, Leticia] Univ Tubingen, Inst Pathol, D-7400 Tubingen, Germany.
[Fend, Falko; Quintanilla-Martinez, Leticia] Univ Tubingen, Ctr Comprehens Canc, Tubingen, Germany.
RP Quintanilla-Martinez, L (reprint author), Univ Tubingen Hosp, Inst Pathol, Liebermeisterstr 8, D-72076 Tubingen, Germany.
EM leticia.quintanilla-fend@med.uni-tuebingen.de
FU Mantle Cell Lymphoma Consortium, Lymphoma Research Foundation, NY;
Technical University Munich
FX this work was supported by a grant from the Mantle Cell Lymphoma
Consortium, Lymphoma Research Foundation, NY (to LQM) and a grant for
female graduate students from the Technical University Munich to JSH.
NR 56
TC 22
Z9 23
U1 1
U2 2
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOL-HEMATOL J
JI Haematol-Hematol. J.
PD SEP
PY 2012
VL 97
IS 9
BP 1422
EP 1430
DI 10.3324/haematol.2011.055715
PG 9
WC Hematology
SC Hematology
GA 007SL
UT WOS:000308908300023
PM 22315488
ER
PT J
AU Neary, NM
El-Maouche, D
Hopkins, R
Libutti, SK
Moses, AM
Weinstein, LS
AF Neary, Nicola M.
El-Maouche, Diala
Hopkins, Rachel
Libutti, Steven K.
Moses, Arnold M.
Weinstein, Lee S.
TI Development and Treatment of Tertiary Hyperparathyroidism in Patients
with Pseudohypoparathyroidism Type 1B
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID PROTEIN ALPHA-SUBUNIT; PARATHYROID-HORMONE; SKELETAL RESPONSIVENESS; IB;
BONE; GNAS
AB Context: Pseudohypoparathyroidism type 1B (PHP1B) patients have PTH resistance at the renal proximal tubule and develop hypocalcemia and secondary hyperparathyroidism. Hyperparathyroid bone disease also develops in some patients. PHP1B patients are at theoretical risk of developing tertiary hyperparathyroidism.
Setting: Patients were studied in a clinical research center.
Patients: Five female PHP1B patients presented with hypercalcemia and elevated PTH.
Intervention: Patients either underwent parathyroidectomy (n = 4) or received cinacalcet (n = 1).
Main Outcome Measures: Serum calcium and PTH were serially measured before and after intervention.
Results: Five PHP1B patients developed concomitantly elevated serum calcium and PTH levels (range, 235-864 ng/liter) requiring termination of calcium and vitamin D therapy (time after diagnosis, 21-42 yr; median, 34 yr), consistent with tertiary hyperparathyroidism. Four patients underwent parathyroidectomy with removal of one (n = 2) or two (n = 2) enlarged parathyroid glands. Calcium and vitamin D therapy was reinstituted postoperatively, and at 93-month median follow-up, PTH levels ranged between 56 and 182 (normal, <87) ng/liter. One patient was treated with cinacalcet, resulting in resolution of hypercalcemia.
Conclusions: PHP1B patients are at risk of developing tertiary hyperparathyroidism and/or hyperparathyroid bone disease and should therefore be treated with sufficient doses of calcium and vitamin D to achieve serum calcium and PTH levels within or as close to the normal range as possible. Surgery is the treatment of choice in this setting. Cinacalcet may be a useful alternative in those who do not undergo surgery. (J Clin Endocrinol Metab 97: 3025-3030, 2012)
C1 [Weinstein, Lee S.] NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA.
[Neary, Nicola M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Reprod Endocrinol, Bethesda, MD 20892 USA.
[Libutti, Steven K.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Hopkins, Rachel; Moses, Arnold M.] Upstate Med Univ, Dept Med, Syracuse, NY 13210 USA.
RP Weinstein, LS (reprint author), NIDDKD, Metab Dis Branch, NIH, Bldg 10,Room 8C101, Bethesda, MD 20892 USA.
EM leew@mail.nih.gov
OI El-Maouche, Diala/0000-0002-0936-2249; Weinstein,
Lee/0000-0002-1899-5152
FU National Institute of Diabetes and Digestive and Kidney Diseases;
National Cancer Institute, National Institutes of Health, Bethesda,
Maryland
FX This work was supported by the Intramural Research Programs of the
National Institute of Diabetes and Digestive and Kidney Diseases and
National Cancer Institute, National Institutes of Health, Bethesda,
Maryland.
NR 14
TC 10
Z9 11
U1 1
U2 2
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD SEP
PY 2012
VL 97
IS 9
BP 3025
EP 3030
DI 10.1210/jc.2012-1655
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 004PF
UT WOS:000308692900036
PM 22736772
ER
PT J
AU Bible, KC
Suman, VJ
Menefee, ME
Smallridge, RC
Molina, JR
Maples, WJ
Karlin, NJ
Traynor, AM
Kumar, P
Goh, BC
Lim, WT
Bossou, AR
Isham, CR
Webster, KP
Kukla, AK
Bieber, C
Burton, JK
Harris, P
Erlichman, C
AF Bible, Keith C.
Suman, Vera J.
Menefee, Michael E.
Smallridge, Robert C.
Molina, Julian R.
Maples, William J.
Karlin, Nina J.
Traynor, Anne M.
Kumar, Priya
Goh, Boon Cher
Lim, Wan-Teck
Bossou, Ayoko R.
Isham, Crescent R.
Webster, Kevin P.
Kukla, Andrea K.
Bieber, Carolyn
Burton, Jill K.
Harris, Pamela
Erlichman, Charles
CA Mayo Phase 2 Consortium Mayo Clini
TI A Multiinstitutional Phase 2 Trial of Pazopanib Monotherapy in Advanced
Anaplastic Thyroid Cancer
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID II TRIAL; CARCINOMA; SORAFENIB
AB Context/Objectives: Pazopanib, an inhibitor of kinases including vascular endothelial growth factor receptor, demonstrated impressive activity in progressive metastatic differentiated thyroid cancer, prompting its evaluation in anaplastic thyroid cancer (ATC).
Design/Setting/Patients/Interventions/Outcome Measures: Preclinical studies, followed by a multicenter single arm phase 2 trial of continuously administered 800 mg pazopanib daily by mouth (designed to provide 90% chance of detecting a response rate of >20% at the 0.10 significance level when the true response rate is >5%), were undertaken. The primary trial end point was Response Evaluation Criteria in Solid Tumors (RECIST) response.
Results: Pazopanib displayed activity in the KTC2 ATC xenograft model, prompting clinical evaluation. Sixteen trial patients were enrolled; 15 were treated: 66.7% were female, median age was 66 yr (range 45-77 yr), and 11 of 15 had progressed through prior systemic therapy. Enrollment was halted, triggered by a stopping rule requiring more than one confirmed RECIST response among the first 14 of 33 potential patients. Four patients required one to two dose reductions; severe toxicities (National Cancer Institute Common Toxicity Criteria-Adverse Events version 3.0 grades >3) were hypertension (13%) and pharyngolaryngeal pain (13%). Treatment was discontinued because of the following: disease progression (12 patients), death due to a possibly treatment-related tumor hemorrhage (one patient), and intolerability (radiation recall tracheitis and uncontrolled hypertension, one patient each). Although transient disease regression was observed in several patients, there were no confirmed RECIST responses. Median time to progression was 62 d; median survival time was 111 d. Two patients are alive with disease 9.9 and 35 months after the registration; 13 died of disease.
Conclusions: Despite preclinical in vivo activity in ATC, pazopanib has minimal single-agent clinical activity in advanced ATC. (J Clin Endocrinol Metab 97: 3179-3184, 2012)
C1 [Bible, Keith C.; Molina, Julian R.; Bossou, Ayoko R.; Isham, Crescent R.; Webster, Kevin P.; Kukla, Andrea K.; Burton, Jill K.; Erlichman, Charles] Mayo Clin Rochester, Div Med Oncol, Rochester, MN 55905 USA.
[Suman, Vera J.] Mayo Clin Rochester, Div Biomed Stat & Informat, Rochester, MN 55905 USA.
[Menefee, Michael E.; Maples, William J.; Bieber, Carolyn] Mayo Clin Florida, Div Med Oncol, Jacksonville, FL 32224 USA.
[Smallridge, Robert C.] Mayo Clin Florida, Div Endocrinol, Jacksonville, FL 32224 USA.
[Karlin, Nina J.] Mayo Clin Arizona, Div Med Oncol, Scottsdale, AZ 85259 USA.
[Traynor, Anne M.] Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53705 USA.
[Kumar, Priya] Univ Minnesota Fairview, Edina, MN 55435 USA.
[Goh, Boon Cher] Natl Univ Singapore Hosp, Singapore 119228, Singapore.
[Goh, Boon Cher] Ctr Translat Expt Therapeut, Singapore 119228, Singapore.
[Lim, Wan-Teck] Natl Canc Ctr Singapore, Singapore 169610, Singapore.
[Harris, Pamela] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Bible, KC (reprint author), Mayo Clin Rochester, Div Med Oncol, 200 1st St SW, Rochester, MN 55905 USA.
EM bible.keith@mayo.edu
FU National Cancer Institute [CA15083, CM62205]
FX This work was supported by National Cancer Institute Grants CA15083 and
CM62205.
NR 19
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U2 2
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PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD SEP
PY 2012
VL 97
IS 9
BP 3179
EP 3184
DI 10.1210/jc.2012-1520
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 004PF
UT WOS:000308692900056
PM 22774206
ER
PT J
AU Gaudet, MM
Falk, RT
Stevens, RD
Gunter, MJ
Bain, JR
Pfeiffer, RM
Potischman, N
Lissowska, J
Peplonska, B
Brinton, LA
Garcia-Closas, M
Newgard, CB
Sherman, ME
AF Gaudet, Mia M.
Falk, Roni T.
Stevens, Robert D.
Gunter, Marc J.
Bain, James R.
Pfeiffer, Ruth M.
Potischman, Nancy
Lissowska, Jolanta
Peplonska, Beata
Brinton, Louise A.
Garcia-Closas, Montserrat
Newgard, Christopher B.
Sherman, Mark E.
TI Analysis of Serum Metabolic Profiles in Women with Endometrial Cancer
and Controls in a Population-Based Case-Control Study
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID BREAST-CANCER; RISK-FACTORS; FATTY-ACIDS; METABONOMIC ANALYSIS;
INSULIN-RESISTANCE; C-PEPTIDE; HPLC-MS; ISOVALERYLCARNITINE; OBESITY;
HUMANS
AB Context: Endometrial cancer is associated with metabolic disturbances related to its underlying risk factors, including obesity and diabetes. Identifying metabolite biomarkers associated with endometrial cancer may have value for early detection, risk assessment, and understanding etiology.
Objective: The objective of the study was to evaluate the reliable measurement of metabolites in epidemiological studies with nonstandardized blood collection; confirm previously reported correlations of metabolites with body size; and assess differences in metabolite levels between cases and controls.
Design: This was the Polish Endometrial Cancer Study (2001-2003).
Setting: This study was a population-based case-control study.
Patients: Patients included 250 cases and 250 controls.
Intervention: The intervention included the measurement of serum metabolite levels of 15 amino acids, 45 acylcarnitines, and nine fatty acids.
Main Outcome Measure: The main outcome measure was endometrial cancer.
Results: Body mass index was correlated with levels of valine (r = 0.26, P = 3.4 x 10(-5)), octenoyl-carnitine (r = 0.24, P = 1.5 x 10(-4)), palmitic acid (r = 0.26, P = 4.4 x 10(-5)), oleic acid (r = 0.28, P = 9.9 x 10(-6)), andstearic acid (r = 0.26, P = 2.9 x 10(-5)) amongcontrols. Only stearic acid was inversely associated with endometrial cancer case status (quartile 4 vs. quartile 1: odds ratio 0.37, 95% confidence interval 0.20-0.69, P for trend = 1.2 x 10(-4)). Levels of the C5-acylcarnitines, octenoyl-carnitine, decatrienoylcarnitine, and linoleic acid were significantly lower in cases than controls (odds ratios ranged from 0.21 to 0.38).
Conclusions: These data demonstrate that previously reported variations in metabolomic profiles with body mass index can be replicated in population-based studies with nonfasting blood collection protocols. We also provide preliminary evidence that large differences in metabolite levels exist between cases and controls, independent of body habitus. Our findings warrant assessment of metabolic profiles, including the candidate markers identified herein, in prospectively collected blood samples to define biomarkers and etiological factors related to endometrial cancer. (J Clin Endocrinol Metab 97: 3216-3223, 2012)
C1 [Gaudet, Mia M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30316 USA.
[Falk, Roni T.; Pfeiffer, Ruth M.; Brinton, Louise A.; Garcia-Closas, Montserrat; Sherman, Mark E.] NCI, NIH, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Stevens, Robert D.; Bain, James R.; Newgard, Christopher B.] Duke Univ, Med Ctr, Sarah W Stedman Nutr & Metab Ctr, Durham, NC 27708 USA.
[Bain, James R.] Duke Univ, Med Ctr, Div Metab Endocrinol & Nutr, Durham, NC 27708 USA.
[Newgard, Christopher B.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27708 USA.
[Newgard, Christopher B.] Duke Univ, Med Ctr, Dept Pharmacol, Durham, NC 27708 USA.
[Newgard, Christopher B.] Duke Univ, Med Ctr, Dept Canc Biol, Durham, NC 27708 USA.
[Gunter, Marc J.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London SW7 2AZ, England.
[Lissowska, Jolanta] Ctr Canc, Dept Canc Epidemiol & Prevent, PL-02781 Warsaw, Poland.
M Sklodowska Curie Inst Oncol, PL-02781 Warsaw, Poland.
[Peplonska, Beata] Nofer Inst Occupat Med, Dept Environm Epidemiol, PL-91348 Lodz, Poland.
RP Gaudet, MM (reprint author), Amer Canc Soc, Epidemiol Res Program, 250 Williams St, Atlanta, GA 30316 USA.
EM mia.gaudet@cancer.org
RI Peplonska, Beata/F-6004-2010; Garcia-Closas, Montserrat /F-3871-2015;
Brinton, Louise/G-7486-2015;
OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton,
Louise/0000-0003-3853-8562; Lissowska, Jolanta/0000-0003-2695-5799;
Bain, James/0000-0002-8917-9187
FU National Cancer Institute (Bethesda, MD)
FX This work was supported by intramural funds from the National Cancer
Institute (Bethesda, MD).
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PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD SEP
PY 2012
VL 97
IS 9
BP 3216
EP 3223
DI 10.1210/jc.2012-1490
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 004PF
UT WOS:000308692900060
PM 22730518
ER
PT J
AU Boyce, AM
Chong, WH
Shawker, TH
Pinto, PA
Linehan, WM
Bhattacharryya, N
Merino, MJ
Singer, FR
Collins, MT
AF Boyce, Alison M.
Chong, William H.
Shawker, Thomas H.
Pinto, Peter A.
Linehan, W. Marsten
Bhattacharryya, Nisan
Merino, Maria J.
Singer, Frederick R.
Collins, Michael T.
TI Characterization and Management of Testicular Pathology in
McCune-Albright Syndrome
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID LEYDIG-CELL TUMOR; STIMULATORY G-PROTEIN; POLYOSTOTIC FIBROUS DYSPLASIA;
LIMITED PRECOCIOUS PUBERTY; ACTIVATING MUTATION; SEXUAL PRECOCITY; FSH
RECEPTOR; BOY; GENE; HYPERPLASIA
AB Context: The testicular phenotype in McCune-Albright syndrome (MAS) has not been well characterized. Boys present with a relatively low incidence of precocious puberty in comparison with girls. Radiographic and histological studies are limited to small series and case reports, which report testicular microlithiasis and Sertoli cell hyperplasia.
Objective: Our objective was to characterize the biochemical, radiological, and histological spectrum and clinical management of testicular pathology in males with MAS.
Patients, Design, and Setting: Fifty-four males with MAS participated in this prospective cohort study at a clinical research center.
Intervention: Evaluation included testicular exam, pubertal staging, testicular ultrasound, measurement of LH, FSH, and testosterone. Orchiectomies were performed when considered clinically indicated.
Main Outcome Measure: Prevalence and characterization of ultrasound lesions with correlation to histology were evaluated.
Results: Of 54 males, 44 (81%) presented with ultrasound abnormalities including hyperechoic lesions (49%), hypoechoic lesions (30%), microlithiasis (30%), heterogeneity (47%), and focal calcifications (11%). Eight subjects underwent orchiectomy revealing large foci of Leydig cell hyperplasia, which could not be definitively distinguished from Leydig cell tumor. After no subjects developed clinical malignancy, a conservative approach was instituted, and subsequent subjects were followed with serial imaging. Testosterone and gonadotropins were normal in subjects without precocious puberty or pituitary disease. Eleven (21%) presented with precocious puberty, and a combination of aromatase inhibitors, androgen receptor blockers, and leuprolide resulted in improved predicted adult height. In addition, the first cases of testicular adrenal rest and bilateral germ cell tumors in association with MAS are presented.
Conclusions: Contrary to prevailing thinking, the incidence of gonadal pathology in MAS is equal in males and females. The predominant histopathological finding was Leydig cell hyperplasia, which carries a low risk of malignant transformation and can be managed conservatively. (J Clin Endocrinol Metab 97: E1782-E1790, 2012)
C1 [Boyce, Alison M.; Chong, William H.; Bhattacharryya, Nisan; Collins, Michael T.] Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA.
[Boyce, Alison M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
[Pinto, Peter A.; Linehan, W. Marsten] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Merino, Maria J.] NIH, Pathol Lab, Bethesda, MD 20892 USA.
[Singer, Frederick R.] John Wayne Canc Inst, Endocrine Bone Dis Program, Santa Monica, CA 90404 USA.
RP Boyce, AM (reprint author), Childrens Natl Med Ctr, Bone Hlth Program, Div Orthopaed & Sports Med, 111 Michigan Ave NW, Washington, DC 20010 USA.
EM boyceam@mail.nih.gov; mcollins@mail.nih.gov
FU National Institute of Dental and Craniofacial Research; National
Institute of Child Health and Development, National Institutes of Health
FX This research was supported by the National Institute of Dental and
Craniofacial Research, and the National Institute of Child Health and
Development, National Institutes of Health.
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SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD SEP
PY 2012
VL 97
IS 9
BP E1782
EP E1790
DI 10.1210/jc.2012-1791
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 004PF
UT WOS:000308692900021
PM 22745241
ER
PT J
AU Golden, SH
Brown, A
Cauley, JA
Chin, MH
Gary-Webb, TL
Kim, C
Sosa, JA
Sumner, AE
Anton, B
AF Golden, Sherita Hill
Brown, Arleen
Cauley, Jane A.
Chin, Marshall H.
Gary-Webb, Tiffany L.
Kim, Catherine
Sosa, Julie Ann
Sumner, Anne E.
Anton, Blair
TI Health Disparities in Endocrine Disorders: Biological, Clinical, and
Nonclinical Factors-An Endocrine Society Scientific Statement
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID GESTATIONAL DIABETES-MELLITUS; NUTRITION EXAMINATION SURVEY;
QUALITY-OF-CARE; AFRICAN-AMERICAN WOMEN; NEW-YORK-CITY; VISCERAL
ADIPOSE-TISSUE; HIP FRACTURE INCIDENCE; NON-HISPANIC WHITES;
DIFFERENTIATED THYROID-CANCER; EARLY PERIMENOPAUSAL WOMEN
AB Objective: The aim was to provide a scholarly review of the published literature on biological, clinical, and nonclinical contributors to race/ethnic and sex disparities in endocrine disorders and to identify current gaps in knowledge as a focus for future research needs.
Participants in Development of Scientific Statement: The Endocrine Society's Scientific Statement Task Force (SSTF) selected the leader of the statement development group (S.H.G.). She selected an eight-member writing group with expertise in endocrinology and health disparities, which was approved by the Society. All discussions regarding the scientific statement content occurred via teleconference or written correspondence. No funding was provided to any expert or peer reviewer, and all participants volunteered their time to prepare this Scientific Statement.
Evidence: The primary sources of data on global disease prevalence are from the World Health Organization. A comprehensive literature search of PubMed identified U. S. population-based studies. Search strategies combining Medical Subject Headings terms and keyword terms and phrases defined two concepts: 1) racial, ethnic, and sex differences including specific populations; and 2) the specific endocrine disorderor condition. The search identified systematic reviews, meta-analyses, large cohort and population-based studies, and original studies focusing on the prevalence and determinants of disparities in endocrine disorders.
Consensus Process: The writing group focused on population differences in the highly prevalent endocrine diseases of type 2 diabetes mellitus and related conditions (prediabetes and diabetic complications), gestational diabetes, metabolicsyndrome with a focus on obesity and dyslipidemia, thyroid disorders, osteoporosis, and vitamin D deficiency. Authors reviewed and synthesized evidence in their areas of expertise. The final statement incorporated responses to several levels of review: 1) comments of the SSTF and the Advocacy and Public Outreach Core Committee; and 2) suggestions offered by the Council and members of The Endocrine Society.
Conclusions: Several themes emerged in the statement, including a need for basic science, population-based, translational and health services studies to explore underlying mechanisms contributing to endocrine health disparities. Compared to non-Hispanic whites, non-Hispanic blacks have worse outcomes and higher mortality from certain disorders despite having a lower(e.g. macrovascular complications of diabetes mellitus and osteoporotic fractures) or similar (e.g. thyroid cancer) incidence of these disorders. Obesity is an important contributor to diabetes risk in minority populations and to sex disparities in thyroid cancer, suggesting that population interventions targeting weight loss may favorably impact a number of endocrine disorders. There are importantimplications regarding the definition of obesity in different race/ethnic groups, including potential underestimation of disease risk in Asian-Americans and overe stimation in non-Hispanic black women. Ethnic-specific cut-points for central obesity should be determined so that clinicians can adequately assess metabolic risk. There is little evidence that genetic differences contribute significantly to race/ethnic disparities in the endocrine disorders examined. Multilevel interventions have reduced disparities in diabetes care, and these successes can be modeled to design similar interventions for other endocrine diseases. (J Clin Endocrinol Metab 97: E1579-E1639, 2012)
C1 [Golden, Sherita Hill] Johns Hopkins Univ, Sch Med, Div Endocrinol & Metab, Dept Med, Baltimore, MD 21287 USA.
[Golden, Sherita Hill] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21287 USA.
[Anton, Blair] Johns Hopkins Univ, Welch Med Lib, Baltimore, MD 21287 USA.
[Brown, Arleen] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA.
[Cauley, Jane A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA.
[Chin, Marshall H.] Univ Chicago, Chicago Ctr Diabet Translat Res, Dept Med, Chicago, IL 60637 USA.
[Gary-Webb, Tiffany L.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY 10032 USA.
[Kim, Catherine] Univ Michigan, Dept Med, Ann Arbor, MI 48105 USA.
[Kim, Catherine] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48105 USA.
[Sosa, Julie Ann] Yale Univ, Dept Surg Endocrine Surg & Surg Oncol, Sch Med, New Haven, CT 06520 USA.
[Sosa, Julie Ann] Yale Univ, Dept Med Oncol, Sch Med, New Haven, CT 06520 USA.
[Sumner, Anne E.] NIDDKD, Diabet Obes & Endocrinol Branch, NIH, Bethesda, MD 20827 USA.
RP Golden, SH (reprint author), Johns Hopkins Univ, Sch Med, Div Endocrinol & Metab, Dept Med, 1830 E Monument St,Suite 333, Baltimore, MD 21287 USA.
EM sahill@jhmi.edu
OI Anton, Blair/0000-0002-7077-6678; Cauley, Jane A/0000-0003-0752-4408
FU Endocrine Society; Johns Hopkins Center to Eliminate Cardiovascular
Health Disparities from the National Heart, Lung, and Blood Institute
[50 HL0105187]; National Center for Research Resources [UL1RR033176];
National Center for Advancing Translational Sciences [UL1TR000124];
Midcareer Investigator Award in Patient-Oriented Research from the
National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK)
[K24 DK071933]; Chicago Center for Diabetes Translation Research [P30
DK092949]; NIDDK [R01DK083297, K23DK071552]; intramural program of
NIDDK, National Institutes of Health (NIH)
FX We thank Jose Florez, M.D., and James Meigs, M.D., MPH, for assistance
in identifying appropriate literature for the diabetes genetics section.
We thank Eric Vohr for his technical writing and organization expertise
in finalizing our statement. We thank Ivy Garner and Claire Twose for
their expertise in information management and referencing assistance. We
thank The Endocrine Society and Loretta Doan, Ph.D., for their support
and guidance in preparing this statement.; S.H.G. was supported by a
Program Project Grant for the Johns Hopkins Center to Eliminate
Cardiovascular Health Disparities from the National Heart, Lung, and
Blood Institute (P50 HL0105187). A.B. was supported by the National
Center for Research Resources (Grant UL1RR033176), which is now at the
National Center for Advancing Translational Sciences (Grant
UL1TR000124). M.H.C. is supported by a Midcareer Investigator Award in
Patient-Oriented Research (K24 DK071933) from the National Institute of
Diabetes, Digestive and Kidney Diseases (NIDDK) and the Chicago Center
for Diabetes Translation Research (P30 DK092949). C.K. is supported by
Grants R01DK083297and K23DK071552 through the NIDDK. A.E.S. is supported
by the intramural program of NIDDK, National Institutes of Health (NIH).
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PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD SEP
PY 2012
VL 97
IS 9
BP E1579
EP E1639
DI 10.1210/jc.2012-2043
PG 61
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 004PF
UT WOS:000308692900001
PM 22730516
ER
PT J
AU Potter, WZ
AF Potter, William Z.
TI Mining the secrets of the CSF: developing biomarkers of
neurodegeneration
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Editorial Material
AB Our ability to track the progression of neurological disorders like Parkinson's disease (PD) is hampered by a lack of biomarkers, rendering the neuronal changes that underlie clinical symptoms largely a mystery. In this issue of the JCI, Fanara et al. report the development of an innovative approach to biomarker development. They describe a method to measure axonal microtubule function via cerebrospinal fluid (CSF) sampling and use this technique to provide evidence of deficiencies in this process in PD patients. This both sheds light on the pathophysiology of PD and has implications for the more general problem of developing biomarkers for any brain process.
C1 [Potter, William Z.] NIMH, Bethesda, MD 20892 USA.
RP Potter, WZ (reprint author), NIMH, 6001 Execut Blvd,BG NSC RM 7209, Rockville, MD 20892 USA.
EM wzpottermd@gmail.com
NR 9
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U1 0
U2 6
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 2012
VL 122
IS 9
BP 3051
EP 3053
DI 10.1172/JCI65309
PG 3
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 002EC
UT WOS:000308513100007
PM 22922253
ER
PT J
AU Petrovas, C
Yamamoto, T
Gerner, MY
Boswell, KL
Wloka, K
Smith, EC
Ambrozak, DR
Sandler, NG
Timmer, KJ
Sun, XY
Pan, L
Poholek, A
Rao, SS
Brenchley, JM
Alam, SM
Tomaras, GD
Roederer, M
Douek, DC
Seder, RA
Germain, RN
Haddad, EK
Koup, RA
AF Petrovas, Constantinos
Yamamoto, Takuya
Gerner, Michael Y.
Boswell, Kristin L.
Wloka, Kaska
Smith, Emily C.
Ambrozak, David R.
Sandler, Netanya G.
Timmer, Katherina J.
Sun, Xiaoyong
Pan, Li
Poholek, Amanda
Rao, Srinivas S.
Brenchley, Jason M.
Alam, S. Munir
Tomaras, Georgia D.
Roederer, Mario
Douek, Daniel C.
Seder, Robert A.
Germain, Ronald N.
Haddad, Elias K.
Koup, Richard A.
TI CD4 T follicular helper cell dynamics during SIV infection
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID IMMUNODEFICIENCY VIRUS-INFECTION; COLONY-STIMULATING FACTOR; BINDING
PROTEIN-ALPHA; GERMINAL CENTER B; C/EBP-ALPHA; PROLIFERATION ARREST;
IMMUNE-RESPONSES; DIFFERENTIATION; RECEPTOR; ACTIVATION
AB CD4 T follicular helper (TFH) cells interact with and stimulate the generation of antigen-specific B cells. TFH cell interaction with B cells correlates with production of SIV-specific immunoglobulins. However, the fate of TFH cells and their participation in SIV-induced antibody production is not well understood. We investigated the phenotype, function, location, and molecular signature of TFH cells in rhesus macaques. Similar to their human counterparts, TFH cells in rhesus macaques represented a heterogeneous population with respect to cytokine function. In a highly differentiated subpopulation of TFH cells, characterized by CD150(lo) expression, production of Th1 cytokines was compromised while IL-4 production was augmented, and cells exhibited decreased survival, cycling, and trafficking capacity. TFH cells exhibited a d.istinct gene profile that was markedly altered by SIV infection. TFH cells were infected by SIV; yet, in some animals, these cells actually accumulated during chronic SIV infection. Generalized immune activation and increased IL-6 production helped drive TFH differentiation during SIV infection. Accumulation of TFH cells was associated with increased frequency of activated germinal center B cells and SIV-specific antibodies. Therefore, chronic SIV does not disturb the ability of TFH cells to help B cell maturation and production of SIV-specific immunoglobulins.
C1 [Petrovas, Constantinos; Yamamoto, Takuya; Boswell, Kristin L.; Wloka, Kaska; Smith, Emily C.; Ambrozak, David R.; Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Gerner, Michael Y.; Poholek, Amanda; Germain, Ronald N.] NIAID, Lab Syst Biol, Lymphocyte Biol Sect, NIH, Bethesda, MD 20892 USA.
[Sandler, Netanya G.; Timmer, Katherina J.; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Sun, Xiaoyong; Pan, Li; Haddad, Elias K.] VGTI Florida, Port St Lucie, FL USA.
[Rao, Srinivas S.] NIAID, Lab Anim Med, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Brenchley, Jason M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Alam, S. Munir; Tomaras, Georgia D.] Duke Univ, Sch Med, Duke Human Vaccine Inst, Durham, NC USA.
[Roederer, Mario] NIAID, ImmunoTechnol Sect, NIH, Bethesda, MD 20892 USA.
[Seder, Robert A.] NIAID, Cellular Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Petrovas, C (reprint author), NIAID, Immunol Lab, Vaccine Res Ctr, NIH, 40 Convent Dr,MSC 3022,Bldg 40,Room 3612B, Bethesda, MD 20892 USA.
EM petrovasc@mail.nih.gov
RI Yamamoto, Takuya/L-2642-2013; Tomaras, Georgia/J-5041-2016;
OI Yamamoto, Takuya/0000-0003-3753-1211; Utay, Netanya/0000-0002-6407-8670
FU Vaccine Research Center; CAVD from the Bill and Melinda Gates Foundation
[OPP1032325]
FX The authors would like to thank the personnel of the Flow Cytometry
Core, the Nonhuman Primate Immunogenicity Core Section, and the
Laboratory Animal Medicine at Vaccine Research Center as well as the
Aids Vaccine Program, SAIC-Frederick Inc., NCI-Frederick, and R. Glenn
Overman, Will Williams, and Shelley Stewart at Duke Human Vaccine
Institute. We would like to thank Adrian B. McDermott and Brenna Hill
for helpful discussions. This research was supported by the Intramural
Research Program of the Vaccine Research Center and a CAVD grant (no.
OPP1032325) from the Bill and Melinda Gates Foundation (to R.A. Koup).
NR 63
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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 2012
VL 122
IS 9
BP 3281
EP 3294
DI 10.1172/JCI63039
PG 14
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 002EC
UT WOS:000308513100028
PM 22922258
ER
PT J
AU Ward, MM
Learch, TJ
Weisman, MH
AF Ward, Michael M.
Learch, Thomas J.
Weisman, Michael H.
TI Cervical Vertebral Squaring in Patients without Spondyloarthritis
SO JOURNAL OF RHEUMATOLOGY
LA English
DT Letter
ID ANKYLOSING-SPONDYLITIS
C1 [Ward, Michael M.] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Learch, Thomas J.; Weisman, Michael H.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
RP Ward, MM (reprint author), NIAMS, NIH, Bldg 10 CRC,Room 4-1339,10 Ctr Dr, Bethesda, MD 20892 USA.
EM wardm1@mail.nih.gov
FU Intramural NIH HHS [ZIA AR041153-07]
NR 4
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U1 0
U2 0
PU J RHEUMATOL PUBL CO
PI TORONTO
PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA
SN 0315-162X
J9 J RHEUMATOL
JI J. Rheumatol.
PD SEP
PY 2012
VL 39
IS 9
BP 1900
EP 1901
DI 10.3899/jrheum.120322
PG 2
WC Rheumatology
SC Rheumatology
GA 005TW
UT WOS:000308774000027
PM 22942307
ER
PT J
AU Weisbrod, AB
Zhang, LS
Jain, M
Barak, S
Quezado, M
Nilubol, N
Kebebew, E
AF Weisbrod, Allison B.
Zhang, Lisa
Jain, Meenu
Barak, Stephanie
Quezado, Martha
Nilubol, Naris
Kebebew, Electron
TI Altered PTEN, CHGA, CHGB and ATRX expression are associated with
aggressive Von Hippel- Lindau-associated pancreatic neuroendocrine
tumors
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Meeting Abstract
CT 98th Annual Clinical Congress of the American-College-of-Surgeons/67th
Annual Sessions of the Owen H Wangensteen Forum on Fundamental Surgical
Problems
CY SEP 30-OCT 04, 2012
CL Chicago, IL
SP Amer Coll Surg
C1 [Weisbrod, Allison B.; Zhang, Lisa; Jain, Meenu; Barak, Stephanie; Quezado, Martha; Nilubol, Naris; Kebebew, Electron] NCI, NIH, 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
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD SEP
PY 2012
VL 215
IS 3
SU S
BP S29
EP S29
PG 1
WC Surgery
SC Surgery
GA 007SX
UT WOS:000308909600046
ER
PT J
AU Liu, YM
Liu, YM
Nguyen, P
Gibbons, A
Mitchell, JB
Poirier, MC
AF Liu, Yongmin
Liu, Yongmin
Phuonggiang Nguyen
Gibbons, Alexander
Mitchell, James B.
Poirier, Miriam C.
TI Tempol as a potential protective agent for nucleoside reverse
transcriptase inhibitor (NRTI)-induced mitochondrial toxicity
SO MITOCHONDRION
LA English
DT Meeting Abstract
C1 [Liu, Yongmin; Phuonggiang Nguyen; Gibbons, Alexander; Poirier, Miriam C.] NCI, Carcinogen DNA Interact Sect, NIH, Bethesda, MD 20892 USA.
[Mitchell, James B.] NCI, LCBG & Tumor Biol Sect, RBB, NIH, Bethesda, MD 20892 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 1567-7249
J9 MITOCHONDRION
JI Mitochondrion
PD SEP
PY 2012
VL 12
IS 5
MA 22
BP 557
EP 558
DI 10.1016/j.mito.2012.07.021
PG 2
WC Cell Biology; Genetics & Heredity
SC Cell Biology; Genetics & Heredity
GA 009KC
UT WOS:000309023700029
ER
PT J
AU Choi, J
Batchu, VVK
Schubert, M
Castellani, RJ
Russell, JW
AF Choi, Joungil
Batchu, Vera Venkatanaresh Kumar
Schubert, Manfred
Castellani, Rudolph J.
Russell, James W.
TI Activation of mitochondrial bioenergetics by 35-kDa PGC-1 alpha/PINK1
signaling pathway
SO MITOCHONDRION
LA English
DT Meeting Abstract
C1 [Choi, Joungil; Batchu, Vera Venkatanaresh Kumar; Russell, James W.] Univ Maryland, Dept Neurol, Baltimore, MD 21201 USA.
[Choi, Joungil; Batchu, Vera Venkatanaresh Kumar; Russell, James W.] Vet Affairs Med Ctr, Baltimore, MD 21201 USA.
[Schubert, Manfred] NINDS, Baltimore, MD 21201 USA.
[Castellani, Rudolph J.] Univ Maryland, Dept Pathol, Baltimore, MD 21201 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1567-7249
J9 MITOCHONDRION
JI Mitochondrion
PD SEP
PY 2012
VL 12
IS 5
MA 56
BP 570
EP 571
DI 10.1016/j.mito.2012.07.053
PG 2
WC Cell Biology; Genetics & Heredity
SC Cell Biology; Genetics & Heredity
GA 009KC
UT WOS:000309023700061
ER
PT J
AU Scheibye-Knudsen, M
Scheibye-Alsing, K
Canugovi, C
Croteau, DL
Bohr, VA
AF Scheibye-Knudsen, Morten
Scheibye-Alsing, Karsten
Canugovi, Chandrika
Croteau, Deborah L.
Bohr, Vilhelm A.
TI An evolving bioinformatics tool reveals mitochondrial pathology in
diseases and aging
SO MITOCHONDRION
LA English
DT Meeting Abstract
C1 [Scheibye-Knudsen, Morten; Canugovi, Chandrika; Croteau, Deborah L.; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
[Scheibye-Alsing, Karsten] Univ Copenhagen, Fac Hlth & Med Sci, IBHV, Sect Genet & Bioinformat, DK-1168 Copenhagen, Denmark.
OI Scheibye-Knudsen, Morten/0000-0002-6637-1280
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 1567-7249
J9 MITOCHONDRION
JI Mitochondrion
PD SEP
PY 2012
VL 12
IS 5
MA 77
BP 578
EP 578
DI 10.1016/j.mito.2012.07.071
PG 1
WC Cell Biology; Genetics & Heredity
SC Cell Biology; Genetics & Heredity
GA 009KC
UT WOS:000309023700079
ER
PT J
AU Mitra, K
Rikhy, R
Lilly, M
Lippincott-Schwartz, J
Chess, D
Balaban, B
AF Mitra, Kasturi
Rikhy, Richa
Lilly, Mary
Lippincott-Schwartz, Jennifer
Chess, David
Balaban, Bob
TI Mitochondrial fission-fusion activities regulate cell fate determination
between proliferation and differentiation: A possible link to
tumorigenesis
SO MITOCHONDRION
LA English
DT Meeting Abstract
C1 [Mitra, Kasturi; Rikhy, Richa; Lilly, Mary; Lippincott-Schwartz, Jennifer] NICHD, NIH, Bethesda, MD USA.
[Mitra, Kasturi; Chess, David; Balaban, Bob] NHLBI, NIH, Bethesda, MD USA.
RI Rikhy, Richa/J-4481-2012
NR 0
TC 0
Z9 0
U1 0
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1567-7249
J9 MITOCHONDRION
JI Mitochondrion
PD SEP
PY 2012
VL 12
IS 5
MA 80
BP 579
EP 579
DI 10.1016/j.mito.2012.07.074
PG 1
WC Cell Biology; Genetics & Heredity
SC Cell Biology; Genetics & Heredity
GA 009KC
UT WOS:000309023700082
ER
PT J
AU Chon, H
Gugliotti, LA
Sakhuja, K
London, M
Cerritelli, SM
Crouch, R
AF Chon, Hyongi
Gugliotti, Lina A.
Sakhuja, Kiran
London, Mariya
Cerritelli, Susana M.
Crouch, Robert.
TI Mitochondrial DNA depleted mouse B cells are defective in the response
to antigen-stimulation
SO MITOCHONDRION
LA English
DT Meeting Abstract
C1 [Chon, Hyongi; Gugliotti, Lina A.; Sakhuja, Kiran; London, Mariya; Cerritelli, Susana M.; Crouch, Robert.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1567-7249
J9 MITOCHONDRION
JI Mitochondrion
PD SEP
PY 2012
VL 12
IS 5
MA 112
BP 590
EP 590
DI 10.1016/j.mito.2012.07.100
PG 1
WC Cell Biology; Genetics & Heredity
SC Cell Biology; Genetics & Heredity
GA 009KC
UT WOS:000309023700108
ER
PT J
AU Huang, P
Pandoli, O
Wang, XS
Wang, Z
Li, ZM
Zhang, CL
Chen, F
Lin, J
Cui, DX
Chen, XY
AF Huang, Peng
Pandoli, Omar
Wang, Xiansong
Wang, Zhe
Li, Zhiming
Zhang, Chunlei
Chen, Feng
Lin, Jing
Cui, Daxiang
Chen, Xiaoyuan
TI Chiral guanosine 5'-monophosphate-capped gold nanoflowers: Controllable
synthesis, characterization, surface-enhanced Raman scattering activity,
cellular imaging and photothermal therapy
SO NANO RESEARCH
LA English
DT Article
DE Gold nanoflower; chirality; surface-enhanced Raman scattering (SERS);
dark-field imaging; photothermal therapy
ID CIRCULAR-DICHROISM; PHOTODYNAMIC THERAPY; SILVER NANOPARTICLES;
ASCORBIC-ACID; NANORODS; CANCER; TEMPLATE; NANOCRYSTALS; ABSORPTION;
NANOTUBES
AB Plasmonics and chirality in metal nanomaterials are intriguing and inspiring phenomena. Nanoscale chirality of metal nanomaterials has emerged as a hot topic in the past several years. Generally, most plasmon-induced circular dichroism (CD) responses of nanomaterials (> 10 nm) have been artificially created by modifying pre-made achiral nanomaterials with chiral agents, because the in situ generation of plasmon-induced CD responses of nanomaterials with larger size (> 10 nm) is not easy. Herein, we report a simple one-pot green synthesis of chiral gold nanoflowers (GNFs) with abundant petal-shaped tips in the chiral reduction environment arising from the presence of chiral guanosine 5'-monophosphate (5'-GMP) and the chiral reducing agent L-ascorbic acid (L-AA). Different reducing agents can impact the shape and chirality of the products. In addition, the size and chirality of the GNFs can be controlled by adjusting the reaction time. The as-synthesized GNFs have good biocompatibility and can be used for surface-enhanced Raman scattering (SERS) enhancement, cellular dark-field imaging and photothermal therapy.
C1 [Huang, Peng; Pandoli, Omar; Wang, Xiansong; Zhang, Chunlei; Chen, Feng; Lin, Jing; Cui, Daxiang] Shanghai Jiao Tong Univ, Natl Key Lab Nano Micro Fabricat Technol, Key Lab Thin Film & Microfabricat, Minist Educ,Inst Micronano Sci & Technol, Shanghai 200240, Peoples R China.
[Huang, Peng; Wang, Zhe; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
[Wang, Zhe] Xiamen Univ, Ctr Mol Imaging & Translat Med, Sch Publ Hlth, Xiamen 361005, Peoples R China.
[Li, Zhiming] Wenzhou Med Coll, Inst Dermatol, Hosp 1, Wenzhou 325000, Peoples R China.
[Li, Zhiming] Wenzhou Med Coll, Dept Dermatol, Hosp 1, Wenzhou 325000, Peoples R China.
RP Cui, DX (reprint author), Shanghai Jiao Tong Univ, Natl Key Lab Nano Micro Fabricat Technol, Key Lab Thin Film & Microfabricat, Minist Educ,Inst Micronano Sci & Technol, Shanghai 200240, Peoples R China.
EM dxcui@sjtu.edu.cn; Shawn.Chen@nih.gov
RI Chen, Feng/D-6406-2012; Huang, Peng/H-9985-2013; 1203, Feng/E-4310-2016;
Huang, Peng/R-2480-2016
OI Pandoli, Omar/0000-0002-2220-7817; Chen, Feng/0000-0002-1162-1684; 1203,
Feng/0000-0002-1162-1684; Huang, Peng/0000-0003-3651-7813
FU National Program on Key Basic Research Project (973 Program)
[2010CB933901]; National Natural Science Foundation of China [51102258,
20803040, 81028009, 31170961]; Chinese Academy of Sciences [2011T2J06];
New Century Excellent Talents of the Ministry of Education of China
[NCET-08-0350]; Zhejiang Provincial Natural Science Foundation
[LY12H11011]
FX This work was supported by the National Program on Key Basic Research
Project (973 Program) (No. 2010CB933901), National Natural Science
Foundation of China (Nos. 51102258, 20803040, 81028009, 31170961),
Chinese Academy of Sciences Professorship for Senior International
Scientists (No. 2011T2J06), New Century Excellent Talents of the
Ministry of Education of China (No. NCET-08-0350), and the Zhejiang
Provincial Natural Science Foundation (No. LY12H11011).
NR 51
TC 33
Z9 34
U1 8
U2 114
PU TSINGHUA UNIV PRESS
PI BEIJING
PA TSINGHUA UNIV, RM A703, XUEYAN BLDG, BEIJING, 10084, PEOPLES R CHINA
SN 1998-0124
J9 NANO RES
JI Nano Res.
PD SEP
PY 2012
VL 5
IS 9
BP 630
EP 639
DI 10.1007/s12274-012-0248-8
PG 10
WC Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science,
Multidisciplinary; Physics, Applied
SC Chemistry; Science & Technology - Other Topics; Materials Science;
Physics
GA 008OX
UT WOS:000308967500005
ER
PT J
AU Svetkey, LP
Ard, JD
Stevens, VJ
Loria, CM
Young, DY
Hollis, JF
Appel, LJ
Brantley, PJ
Kennedy, BM
Kumanyika, SK
Batch, BC
Corsino, L
Lien, LF
Vollmer, WM
AF Svetkey, Laura P.
Ard, Jamy D.
Stevens, Victor J.
Loria, Catherine M.
Young, Deb Y.
Hollis, Jack F.
Appel, Lawrence J.
Brantley, Phillip J.
Kennedy, Betty M.
Kumanyika, Shiriki K.
Batch, Bryan C.
Corsino, Leonor
Lien, Lillian F.
Vollmer, William M.
CA Weight Loss Maintenance Collaborat
TI Predictors of Long-Term Weight Loss in Adults With Modest Initial Weight
Loss, by Sex and Race
SO OBESITY
LA English
DT Article
ID LIFE-STYLE MODIFICATION; LOSS MAINTENANCE TRIAL; BLOOD-PRESSURE;
CLINICAL-TRIAL; HEART-DISEASE; HYPERTENSION PREVENTION; DIETARY
PATTERNS; OBESITY; RISK; PREVALENCE
AB Effective weight management interventions could reduce race-sex disparities in cardiovascular disease (CVD), yet little is known about factors associated with successful weight loss maintenance in race-sex subgroups. In the Weight Loss Maintenance trial (WLM), overweight/obese (BMI 25-45 kg/m(2)) adults who lost >= 4kg in a 6-month behavioral weight loss intervention (phase I) were randomized into one of three 30-month maintenance interventions (phase II). To investigate predictors in subgroups, randomized groups were combined for this analysis. Of 1,685 phase I participants, 1,032 (61%) entered phase II, including 12% black men (BM), 26% black women (BW), 25% white men (WM), and 37% white women (WW). Weight change over the 36-month study ranged from -2.3% (95% confidence interval = -3.1 to -1.5%) in BW to -4.5% (95% confidence interval = -5.7 to -4.0%) in WM, the result of differential weight loss during phase I. Within race, men lost significantly more weight than women, but within sex group, weight loss did not differ significantly between races. Although participants regained weight during phase II, regain did not differ by race-sex group, and mean weight at the end of the study was significantly lower than phase I entry weight for each subgroup. In regression models, phase I weight loss predicted overall 36-month weight loss in all race-sex groups. Healthy dietary pattern at entry, improvement in dietary pattern, or both were predictive in three of four race-sex groups. Few other variables other than initial weight loss and dietary pattern were predictive. Future research should identify additional modifiable influences on long-term maintenance after a modest weight loss.
C1 [Svetkey, Laura P.; Batch, Bryan C.; Corsino, Leonor; Lien, Lillian F.] Duke Univ, Med Ctr, Sarah W Stedman Nutr & Metab Ctr, Durham, NC 27710 USA.
[Svetkey, Laura P.] Duke Univ, Med Ctr, Dept Med, Duke Hypertens Ctr,Div Nephrol, Durham, NC 27710 USA.
[Ard, Jamy D.] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA.
[Ard, Jamy D.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
[Stevens, Victor J.; Hollis, Jack F.; Vollmer, William M.] Kaiser Permanente NW, Ctr Hlth Res, Hlth Sci Programs, Portland, OR USA.
[Loria, Catherine M.] NHLBI, Bethesda, MD 20892 USA.
[Young, Deb Y.] Univ Maryland, Sch Publ Hlth, Dept Epidemiol & Biostat, College Pk, MD 20742 USA.
[Appel, Lawrence J.] Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA.
[Brantley, Phillip J.] Pennington Biomed Res Ctr, Dept Behav Med, Baton Rouge, LA USA.
[Kennedy, Betty M.] Louisiana Sch Boards Assoc, Baton Rouge, LA USA.
[Kumanyika, Shiriki K.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Dept Epidemiol, Philadelphia, PA 19104 USA.
[Batch, Bryan C.; Corsino, Leonor; Lien, Lillian F.] Duke Univ, Med Ctr, Dept Med, Div Endocrinol Nutr & Metab, Durham, NC 27710 USA.
RP Svetkey, LP (reprint author), Duke Univ, Med Ctr, Sarah W Stedman Nutr & Metab Ctr, Durham, NC 27710 USA.
EM svetk001@mc.duke.edu
FU National Heart, Lung, Blood Institute [5-U01 HL68734, 5-U01 HL68676,
5-U01 HL68790, 5-U01 HL68920, 5-HL68955]
FX The Weight Loss Maintenance trial was sponsored by National Heart, Lung,
Blood Institute grants 5-U01 HL68734, 5-U01 HL68676, 5-U01 HL68790,
5-U01 HL68920, and 5-HL68955.
NR 49
TC 20
Z9 20
U1 1
U2 12
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD SEP
PY 2012
VL 20
IS 9
BP 1820
EP 1828
DI 10.1038/oby.2011.88
PG 9
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 998ZO
UT WOS:000308279100011
PM 21527896
ER
PT J
AU McManus, DD
Lyass, A
Ingelsson, E
Massaro, JM
Meigs, JB
Aragam, J
Benjamin, EJ
Vasan, RS
AF McManus, David D.
Lyass, Asya
Ingelsson, Erik
Massaro, Joseph M.
Meigs, James B.
Aragam, Jayashri
Benjamin, Emelia J.
Vasan, Ramachandran S.
TI Relations of Circulating Resistin and Adiponectin and Cardiac Structure
and Function: The Framingham Offspring Study
SO OBESITY
LA English
DT Article
ID CONGESTIVE-HEART-FAILURE; LEFT ATRIAL SIZE; LEFT-VENTRICULAR
HYPERTROPHY; M-MODE ECHOCARDIOGRAPHY; INSULIN-RESISTANCE;
MYOCARDIAL-INFARCTION; INFLAMMATORY MARKERS; PLASMA ADIPONECTIN; SERUM
RESISTIN; ADIPOSE-TISSUE
AB Obesity is associated with pathological cardiac remodeling and risk of heart failure (HF). Adipocytokines (ADKs) may mediate the increased risk of cardiovascular disease associated with excess adiposity. Yet data relating ADKs to cardiac remodeling phenotypes are sparse. We related two circulating ADKs, resistin and adiponectin, to three important echocardiographic markers of cardiac remodeling, left ventricular mass (LVM), left atrial diameter (LAD), and LV fractional shortening (LVFS) in 2,615 participants (mean age 61 years, 55% women) in the Framingham Offspring Study. Adiponectin concentrations were inversely related to LVM in multivariable linear regression models adjusting for key clinical correlates including BMI (regression coefficient per s.d.-increment in In-adiponectin = -3.37, P = 0.02; P for trend across quartiles = 0.02). Adiponectin was not associated with LAD or LVFS (P > 0.56). Resistin concentrations were inversely related to LVFS (regression coefficient per s.d.-increment in In-resistin = -0.01, P = 0.03; P for trend across quartiles = 0.04). Resistin was not associated with LVM or LAD (P > 0.05). In our moderate-sized, community-based sample, higher circulating concentrations of adiponectin and resistin were associated with lower LVM and lower LVFS, respectively. In conclusion, these associations identify potential mechanisms by which excess adiposity may mediate adverse cardiac remodeling and HF risk.
C1 [McManus, David D.; Lyass, Asya; Massaro, Joseph M.; Aragam, Jayashri; Benjamin, Emelia J.; Vasan, Ramachandran S.] NHLBI, Framingham, MA USA.
[McManus, David D.; Lyass, Asya; Massaro, Joseph M.; Aragam, Jayashri; Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Framingham Heart Study, Framingham, MA USA.
[Lyass, Asya; Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Massaro, Joseph M.] Boston Univ, Dept Math, Sch Publ Hlth, Boston, MA 02215 USA.
[Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Meigs, James B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
[Aragam, Jayashri] Vet Adm Hosp, W Roxbury, MA USA.
[Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA.
[Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA.
RP Vasan, RS (reprint author), NHLBI, Framingham, MA USA.
EM vasan@bu.edu
OI Massaro, Joseph/0000-0002-2682-4812; Ramachandran,
Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336
FU National Heart, Lung and Blood Institute's Framingham Heart Study,
Framingham, MA [N01-HC-25195, 6R01-NS 17950, 2 K24 HL04334, RO1HL080124,
RO1DK80739]
FX This work was supported by the National Heart, Lung and Blood
Institute's Framingham Heart Study (contract no. N01-HC-25195), 6R01-NS
17950, 2 K24 HL04334, RO1HL080124, RO1DK80739 (R.S.V.), Framingham, MA.
NR 45
TC 24
Z9 26
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 2012
VL 20
IS 9
BP 1882
EP 1886
DI 10.1038/oby.2011.32
PG 5
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 998ZO
UT WOS:000308279100020
PM 21350435
ER
PT J
AU Moore, SC
Gunter, MJ
Daniel, CR
Reddy, KS
George, PS
Yurgalevitch, S
Devasenapathy, N
Ramakrishnan, L
Chatterjee, N
Chanock, SJ
Berndt, SI
Mathew, A
Prabhakaran, D
Sinha, R
AF Moore, Steven C.
Gunter, Marc J.
Daniel, Carrie R.
Reddy, K. Srinath
George, Preeti S.
Yurgalevitch, Susan
Devasenapathy, Niveditha
Ramakrishnan, Lakshmy
Chatterjee, Nilanjan
Chanock, Stephen J.
Berndt, Sonja I.
Mathew, Aleyamma
Prabhakaran, Dorairaj
Sinha, Rashmi
TI Common Genetic Variants and Central Adiposity Among Asian-Indians
SO OBESITY
LA English
DT Article
ID BODY-MASS INDEX; FTO RS9939609 POLYMORPHISM; OBESITY-RELATED TRAITS;
TYPE-2 DIABETES RISK; PHYSICAL-ACTIVITY; INSULIN-RESISTANCE;
ENERGY-INTAKE; CARDIOVASCULAR RISK; GLUCOSE-LEVELS; FAT MASS
AB Recent studies have identified common genetic variants that are unequivocally associated with central adiposity, BMI, and/or fasting plasma glucose among individuals of European descent. Our objective was to evaluate these associations in a population of Asian-Indians. We examined 16 single-nucleotide polymorphisms (SNPs) from loci previously linked to waist circumference, BMI, or fasting glucose in 1,129 Asian-Indians from New Delhi and Trivandrum. Trained medical staff measured waist circumference, height, and weight. Fasting plasma glucose was measured from collected blood specimens. Genotype-phenotype associations were evaluated using linear regression, with adjustments for age, gender, religion, and study region. For gene-environment interaction tests, total physical activity (PA) during the past 7 days was assessed by the International Physical Activity Questionnaire (IPAQ). The T allele at the FTO rs3751812 locus was associated with increased waist circumference (per allele effect of +1.58cm, P-trend = 0.0015) after Bonferroni adjustment for multiple testing (P-adj = 0.04). We also found a nominally statistically significant FTO-PA interaction (P-interaction = 0.008). Among participants with <81 metabolic equivalent (MET)-h/wk of PA, the rs3751812 variant was associated with increased waist size (+2.68 cm; 95% confidence interval (CI) = 1.24, 4.12), but not among those with 212+ MET-h/wk (-1.79cm; 95% Cl = -4.17, 0.58). No other variant had statistically significant associations, although statistical power was modest. In conclusion, we confirmed that an FTO variant associated with central adiposity in European populations is associated with central adiposity among Asian-Indians and corroborated prior reports indicating that high PA attenuates FTO-related genetic susceptibility to adiposity.
C1 [Moore, Steven C.; Daniel, Carrie R.; Chatterjee, Nilanjan; Chanock, Stephen J.; Berndt, Sonja I.; Sinha, Rashmi] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA.
[Gunter, Marc J.] Albert Einstein Coll Med, New York, NY USA.
[Reddy, K. Srinath; Ramakrishnan, Lakshmy] All India Inst Med Sci, New Delhi, India.
[Devasenapathy, Niveditha; Prabhakaran, Dorairaj] Ctr Chron Dis Control, New Delhi, India.
[George, Preeti S.; Mathew, Aleyamma] Reg Canc Ctr, Trivandrum 695011, Kerala, India.
[Yurgalevitch, Susan] WESTAT Corp, Rockville, MD 20850 USA.
RP Moore, SC (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA.
EM moorest@mail.nih.gov
RI Sinha, Rashmi/G-7446-2015; Moore, Steven/D-8760-2016;
OI Sinha, Rashmi/0000-0002-2466-7462; Moore, Steven/0000-0002-8169-1661;
Prabhakaran, Dorairaj/0000-0002-3172-834X
FU NIH, National Cancer Institute
FX The author's contributions were as follows-S.C.M.: statistical analysis,
interpretation of results, writing of the manuscript; N.D. and P.S.G.:
study implementation; L.R.: laboratory analysis; M.J.G., C.R.D., N.C.,
S.J.C., and SIB.: interpretation of results; S.Y.: data management and
study coordination; R.S., D.P., A.M., N.C., K.S.R.: study design and
concept; and all authors: critical review and approval of the final
manuscript. We are indebted to the participants of the India Health
Study and we thank Mary McAdams for her tireless support. This research
was supported (in part) by the Intramural Research Program of the NIH,
National Cancer Institute.
NR 40
TC 9
Z9 10
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD SEP
PY 2012
VL 20
IS 9
BP 1902
EP 1908
DI 10.1038/oby.2011.238
PG 7
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 998ZO
UT WOS:000308279100023
PM 21799482
ER
PT J
AU Djousse, L
Bartz, TM
Ix, JH
Zieman, SJ
Delaney, JA
Mukamal, KJ
Gottdiener, JS
Siscovick, DS
Kizer, JR
AF Djousse, Luc
Bartz, Traci M.
Ix, Joachim H.
Zieman, Susan J.
Delaney, Joseph A.
Mukamal, Kenneth J.
Gottdiener, John S.
Siscovick, David S.
Kizer, Jorge R.
TI Adiposity and Incident Heart Failure in Older Adults: the Cardiovascular
Health Study
SO OBESITY
LA English
DT Article
ID UNITED-STATES; INSULIN-RESISTANCE; ABDOMINAL OBESITY; LIFETIME RISK;
DISEASE; HOSPITALIZATION; MORTALITY; EPIDEMIOLOGY; ASSOCIATION;
POPULATION
AB While several studies have reported a positive association between overall adiposity and heart failure (HF) risk, limited and inconsistent data are available on the relation between central adiposity and incident HF in older adults. We sought to examine the association between waist circumference (WC) and incident HF and assess whether sex modifies the relation between WC and HF. Prospective study using data on 4,861 participants of the Cardiovascular Health Study (1989-2007). HF was adjudicated by a committee using information from medical records and medications. We used Cox proportional hazard models to compute hazard ratio (HR). The mean age was 73.0 years for men and 72.3 years for women; 42.5% were men and 15.3% were African Americans. WC was positively associated with an increased risk of HF: each standard deviation of WC was associated with a 14% increased risk of HF (95% Cl: 3%-26%) in a multivariable model. There was not a statistically significant sex-by-WC interaction (P = 0.081). BMI was positively associated with incident HF (HR: 1.22 (95% Cl: 1.15-1.29) per standard deviation increase of BMI); however, this association was attenuated and became nonstatistically significant upon additional adjustment for WC (HR: 1.09 (95% Cl: 0.99-1.21)). In conclusion, a higher WC is associated with an increased risk of HF independent of BMI in community-living older men and women.
C1 [Djousse, Luc] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA.
[Djousse, Luc; Mukamal, Kenneth J.] Harvard Univ, Sch Med, Boston, MA USA.
[Djousse, Luc] Geriatr Res Educ & Clin Ctr, Boston, MA USA.
[Djousse, Luc] Massachusetts Vet Epidemiol & Res Informat Ctr, Boston Vet Affairs Healthcare Syst, Boston, MA USA.
[Bartz, Traci M.] Univ Washington, Sch Publ Hlth & Community Med, Dept Biostat, Seattle, WA 98195 USA.
[Ix, Joachim H.] Univ Calif San Diego, Div Nephrol, San Diego, CA 92103 USA.
[Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA USA.
[Zieman, Susan J.] NIA, NIH, Bethesda, MD 20892 USA.
[Delaney, Joseph A.] Univ Florida, Coll Pharm, Dept Pharmaceut Outcomes & Policy, Gainesville, FL USA.
[Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA.
[Gottdiener, John S.] Univ Maryland, Med Ctr, Div Cardiol, Baltimore, MD 21201 USA.
[Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Kizer, Jorge R.] Weill Cornell Med Coll, Dept Med, New York, NY USA.
[Kizer, Jorge R.] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY USA.
RP Djousse, L (reprint author), Brigham & Womens Hosp, Dept Med, Div Aging, 75 Francis St, Boston, MA 02115 USA.
EM ldjousse@rics.bwh.harvard.edu
RI Djousse, Luc/F-5033-2017
OI Djousse, Luc/0000-0002-9902-3047
FU National Heart Lung Blood Institute [R01HL094555]; [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];
[N01-HC-85239]; [N01-HC-55222]; [U01 HL080295]
FX The research reported in this article was supported by the National
Heart Lung Blood Institute (R01HL094555) to Drs Djousse, Ix, Mukamal,
Zieman, and Kizer. Additional support was provided by contracts
N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01
HC-55222; N01-HC-75150, N01-HC-45133, N01-HC-85239, N01-HC-55222, U01
HL080295, and with additional contribution from the National Institute
of Neurological Disorders and Stroke.
NR 38
TC 8
Z9 8
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD SEP
PY 2012
VL 20
IS 9
BP 1936
EP 1941
DI 10.1038/oby.2011.320
PG 6
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 998ZO
UT WOS:000308279100028
PM 22016094
ER
PT J
AU Mukundan, H
Kumar, S
Price, DN
Ray, SM
Lee, YJ
Min, S
Eum, S
Kubicek-Sutherland, J
Resnick, JM
Grace, WK
Anderson, AS
Hwang, SH
Cho, SN
Via, LE
Barry, C
Sakamuri, R
Swanson, BI
AF Mukundan, Harshini
Kumar, Sandeep
Price, Dominique N.
Ray, Sonja M.
Lee, Ye-Jin
Min, Seonyeong
Eum, Seokyong
Kubicek-Sutherland, Jessica
Resnick, Jesse M.
Grace, W. Kevin
Anderson, Aaron S.
Hwang, Soo Hee
Cho, Sang Nae
Via, Laura E.
Barry, Clifton, III
Sakamuri, Ramamurthy
Swanson, Basil I.
TI Rapid detection of Mycobacterium tuberculosis biomarkers in a sandwich
immunoassay format using a waveguide-based optical biosensor
SO TUBERCULOSIS
LA English
DT Article
DE Tuberculosis; Diagnosis; Lipoarabinomannan; Early secretory antigenic
target 6; Antigen 85 complex; Waveguide-based optical biosensor
ID ANTIGEN-85 COMPLEX; PULMONARY TUBERCULOSIS; PATHOGEN DETECTION;
LIPOARABINOMANNAN; URINE; PREVALENCE; COMPONENTS; INFLUENZA; DIAGNOSIS;
UREIDE
AB Early diagnosis of active tuberculosis (TB) remains an elusive challenge, especially in individuals with disseminated TB and HIV co-infection. Recent studies have shown a promise for the direct detection of pathogen-specific biomarkers such as lipoarabinomannan (LAM) for the diagnosis of TB in HIV-positive individuals. Currently, traditional immunoassay platforms that suffer from poor sensitivity and high nonspecific interactions are used for the detection of such biomarkers. In this manuscript, we demonstrate the development of sandwich immunoassays for the direct detection of three TB-specific biomarkers, namely LAM, early secretory antigenic target 6 (ESAT6) and antigen 85 complex (Ag85), using a waveguide-based optical biosensor platform. Combining detection within the evanescent field of a planar optical waveguide with functional surfaces that reduce non-specific interactions allows for the ultra-sensitive and quantitative detection of biomarkers (an order of magnitude enhanced sensitivity, as compared to plate-based ELISA) in complex patient samples (urine, serum) within a short time. We also demonstrate the detection of LAM in urine from a small sample of subjects being treated for TB using this approach with excellent sensitivity and 100% corroboration with disease status. These results suggest that pathogen-specific biomarkers can be applied for the rapid and effective diagnosis of disease. It is likely that detection of a combination of biomarkers offers greater reliability of diagnosis, rather than detection of any single pathogen biomarker. NCT00341601. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Mukundan, Harshini] Los Alamos Natl Lab, C PCS, Div Chem, Los Alamos, NM 87545 USA.
[Ray, Sonja M.; Via, Laura E.; Barry, Clifton, III] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD USA.
[Lee, Ye-Jin; Min, Seonyeong; Eum, Seokyong; Cho, Sang Nae] Int TB Res Ctr, Masan, South Korea.
[Hwang, Soo Hee] Natl Masan TB Hosp, Masan, South Korea.
[Cho, Sang Nae] Yonsei Univ, Coll Med, Dept Microbiol, Seoul, South Korea.
RP Mukundan, H (reprint author), Los Alamos Natl Lab, C PCS, Div Chem, MS J567, Los Alamos, NM 87545 USA.
EM Harshini@lanl.gov; basil@lanl.gov
RI Barry, III, Clifton/H-3839-2012; Sakamuri, Rama Murthy/D-8919-2012;
OI Sakamuri, Rama Murthy/0000-0002-1640-0709; Via,
Laura/0000-0001-6074-9521; Kubicek-Sutherland,
Jessica/0000-0001-6215-4871
FU Intramural Research Program of the NIAID, NIH; South Korean Ministry of
Health, Welfare and Family Affairs; WHO/FIND [A50452]; Special Programme
for Research and Training in Tropical Diseases; Department of Energy;
Los Alamos National Laboratory LDRD Directed Research Award
FX This work was supported in part, by the Intramural Research Program of
the NIAID, NIH (CEB) and the South Korean Ministry of Health, Welfare
and Family Affairs (CEB and SNC), a WHO/FIND grant A50452 to CEB;
Special Programme for Research and Training in Tropical Diseases (TDR),
and a Department of Energy and Los Alamos National Laboratory LDRD
Directed Research Award to Drs. B. T. Korber and B. I. Swanson. The
authors sincerely thank the many patients that have been willing to
sacrifice their time and energy to contribute to this study and the
doctors and nurses of the National Masan Tuberculosis Hospital that made
this work possible. We thank the BEI Resources Materials Consortium at
the Colorado State University for the reagents (antigens and antibodies)
used in this study. We thank Dr. Jurgen Schmidt (LANL) for many
technical discussions and suggestions. We also thank Ms. Lisa Goldfelder
(NIAID) for assistance with the human research documentation.
NR 29
TC 22
Z9 23
U1 1
U2 39
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 1472-9792
J9 TUBERCULOSIS
JI Tuberculosis
PD SEP
PY 2012
VL 92
IS 5
BP 407
EP 416
DI 10.1016/j.tube.2012.05.009
PG 10
WC Immunology; Microbiology; Respiratory System
SC Immunology; Microbiology; Respiratory System
GA 998PH
UT WOS:000308252400008
PM 22710249
ER
PT J
AU Richt, JA
Feldmann, H
AF Richt, J. A.
Feldmann, H.
TI Changing Realities in Emerging Zoonoses INTRODUCTION
SO ZOONOSES AND PUBLIC HEALTH
LA English
DT Editorial Material
DE Emerging zoonoses; One-Health; conference; disease outbreaks; epidemic;
pandemic
C1 [Richt, J. A.; Feldmann, H.] Kansas State Univ, Diagnost Med Pathobiol Dept, Coll Vet Med, Manhattan, KS 66506 USA.
Natl Inst Allergy & Infect Dis, Natl Inst Hlth, Div Intramural Res, Virol Lab, Hamilton, MT USA.
RP Richt, JA (reprint author), Kansas State Univ, Diagnost Med Pathobiol Dept, Coll Vet Med, Manhattan, KS 66506 USA.
EM jricht@vet.k-state.edu
FU Intramural NIH HHS [Z99 AI999999]
NR 0
TC 0
Z9 0
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1863-1959
J9 ZOONOSES PUBLIC HLTH
JI Zoonoses Public Health
PD SEP
PY 2012
VL 59
SU 2
SI SI
BP 1
EP 1
DI 10.1111/j.1863-2378.2012.01529.x
PG 1
WC Public, Environmental & Occupational Health; Infectious Diseases;
Veterinary Sciences
SC Public, Environmental & Occupational Health; Infectious Diseases;
Veterinary Sciences
GA 003BB
UT WOS:000308582000001
PM 22958246
ER
PT J
AU Kahn, RE
Morozov, I
Feldmann, H
Richt, JA
AF Kahn, R. E.
Morozov, I.
Feldmann, H.
Richt, J. A.
TI 6th International Conference on Emerging Zoonoses
SO ZOONOSES AND PUBLIC HEALTH
LA English
DT Review
DE Zoonoses; bacteria; prions; influenza viruses; pathogens; wildlife
ID WEST-NILE-VIRUS; BOVINE SPONGIFORM ENCEPHALOPATHY; RIFT-VALLEY FEVER;
NORTHEASTERN UNITED-STATES; SWINE INFLUENZA-VIRUSES; NERVOUS-SYSTEM;
CELL-DEATH; INTERSPECIES TRANSMISSION; RESTON-EBOLAVIRUS;
ANOPHELES-GAMBIAE
AB The 6th International Conference on Emerging Zoonoses, held at Cancun, Mexico, 2427 February 2011, offered 84 participants from 18 countries, a snapshot of current research in numerous zoonoses caused by viruses, bacteria or prions. Co-chaired by Professors Heinz Feldmann and Jurgen Richt, the conference explored 10 topics: (i) The ecology of emerging zoonotic diseases; (ii) The role of wildlife in emerging zoonoses; (iii) Cross-species transmission of zoonotic pathogens; (iv) Emerging and neglected influenza viruses; (v) Haemorrhagic fever viruses; (vi) Emerging bacterial diseases; (vii) Outbreak responses to zoonotic diseases; (viii) Food-borne zoonotic diseases; (ix) Prion diseases; and (x) Modelling and prediction of emergence of zoonoses. Human medicine, veterinary medicine and environmental challenges are viewed as a unity, which must be considered under the umbrella of One Health. Several presentations attempted to integrate the insights gained from field data with mathematical models in the search for effective control measures of specific zoonoses. The overriding objective of the research presentations was to create, improve and use the tools essential to address the risk of contagions in a globalized society. In seeking to fulfil this objective, a three-step approach has often been applied: (i) use cultured cells, model and natural animal hosts and human clinical models to study infection; (ii) combine traditional histopathological and biochemical approaches with functional genomics, proteomics and computational biology; and (iii) obtain signatures of virulence and insights into mechanisms of host defense response, immune evasion and pathogenesis. This meeting review summarizes 39 of the conference presentations and mentions briefly the 16 articles in this Special Supplement, most of which were presented at the conference in earlier versions. The full affiliations of all presenters and many colleagues have been included to facilitate further inquiries from readers.
C1 [Kahn, R. E.; Morozov, I.; Richt, J. A.] Kansas State Univ, Coll Vet Med, Diagnost Med Pathobiol Dept, Manhattan, KS 66506 USA.
[Feldmann, H.] NIAID, Rocky Mt Labs, Virol Lab, Hamilton, MT 59840 USA.
RP Richt, JA (reprint author), Kansas State Univ, Coll Vet Med, Med Pathobiol Dept, K224B Mosier Hall, Manhattan, KS 66506 USA.
EM jricht@vet.k-state.edu
FU MedImmune; Boehringer Ingelheim Vetmedica GmbH; Prionics AG; Center of
Excellence for Emerging and Zoonotic Animal Diseases (CEEZAD); National
Center for Foreign Animal and Zoonotic Disease Defense (FAZD); U.S.
Department of Homeland Security [2010-ST-AG0001]; Kansas Bioscience
Authority
FX The Organizing Committee of the Conference wishes to acknowledge the
excellent services of the Conference Organizers, Target Conferences of
Tel Aviv, Israel, and the welcome financial contributions of MedImmune,
Boehringer Ingelheim Vetmedica GmbH, Prionics AG, Center of Excellence
for Emerging and Zoonotic Animal Diseases (CEEZAD) and National Center
for Foreign Animal and Zoonotic Disease Defense (FAZD), as well as the
Poster Prize donated by Wiley-Blackwell. We are also grateful to the
Wiley-Blackwell staff who have contributed so significantly to this
Special Supplement, especially Rachel Robinson and Peter Tubman, as well
as to Dr. Klaus Osterrieder for his helpful comments and to the
presenters who have approved or improved every summary in this Meeting
Review. This material is based upon work supported by the U.S.
Department of Homeland Security under Grant Award Number
2010-ST-AG0001.; The views and conclusions contained in this Supplement
are those of the authors and should not be interpreted as necessarily
representing the official policies, either expressed or implied, of the
U.S. Department of Homeland Security. Additional funding has been
provided by the Kansas Bioscience Authority.
NR 154
TC 1
Z9 1
U1 1
U2 29
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1863-1959
EI 1863-2378
J9 ZOONOSES PUBLIC HLTH
JI Zoonoses Public Health
PD SEP
PY 2012
VL 59
SU 2
SI SI
BP 2
EP 31
DI 10.1111/j.1863-2378.2012.01539.x
PG 30
WC Public, Environmental & Occupational Health; Infectious Diseases;
Veterinary Sciences
SC Public, Environmental & Occupational Health; Infectious Diseases;
Veterinary Sciences
GA 003BB
UT WOS:000308582000002
PM 22958247
ER
PT J
AU Sogoba, N
Feldmann, H
Safronetz, D
AF Sogoba, N.
Feldmann, H.
Safronetz, D.
TI Lassa Fever in West Africa: Evidence for an Expanded Region of
Endemicity
SO ZOONOSES AND PUBLIC HEALTH
LA English
DT Review
DE Lassa fever; West Africa; Mastomys natalensis; endemicity
ID VIRUS DISEASE; PATHOGENESIS; STRAIN
AB Lassa virus (LASV) is endemic in Sierra Leone, Guinea and Liberia (known as the Mano River region) and Nigeria and Lassa fever cases from these countries are being reported annually. Recent investigations have found evidence for an expanded endemicity zone between the two known Lassa endemic regions indicating that LASV is more widely distributed throughout the Tropical Wooded Savanna ecozone in West Africa.
C1 [Feldmann, H.; Safronetz, D.] NIAID, Virol Lab, Div Intramural Res, Rocky Mt Labs,NIH, Hamilton, MT USA.
[Sogoba, N.] Univ Bamako, Malaria Res & Training Ctr, Fac Med Pharm & Dent, Bamako, Mali.
RP Safronetz, D (reprint author), NIAID, Virol Lab, Div Intramural Res, Rocky Mt Labs,NIH, Hamilton, MT USA.
EM safronetzd@niaid.nih.gov
NR 28
TC 18
Z9 18
U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1863-1959
J9 ZOONOSES PUBLIC HLTH
JI Zoonoses Public Health
PD SEP
PY 2012
VL 59
SU 2
SI SI
BP 43
EP 47
DI 10.1111/j.1863-2378.2012.01469.x
PG 5
WC Public, Environmental & Occupational Health; Infectious Diseases;
Veterinary Sciences
SC Public, Environmental & Occupational Health; Infectious Diseases;
Veterinary Sciences
GA 003BB
UT WOS:000308582000004
PM 22958249
ER
PT J
AU Resnik, DB
Dinse, GE
AF Resnik, David B.
Dinse, Gregg E.
TI Do US Research Institutions Meet or Exceed Federal Mandates for
Instruction in Responsible Conduct of Research? A National Survey
SO ACADEMIC MEDICINE
LA English
DT Article
AB Purpose
To explore the extent to which U. S. research institutions are meeting or exceeding National Institutes of Health and National Science Foundation mandates to provide instruction in responsible conduct of research (RCR).
Method
In summer 2011, the authors sent an e-mail survey to officials responsible for overseeing RCR instructional programs at the 200 top-funded research institutions in the United States and Puerto Rico. They cross-classified the proportions exceeding federal mandates by the types of additional individuals required to receive training and by medical school presence/absence.
Results
Responses were received from 144 institutions (72%); all had an RCR program. Of these 144 institutions, 69 (47.9%) required only federally mandated individuals to take RCR training, whereas 75 (52.1%) required additional individuals to be trained as well. A greater proportion of institutions with medical schools (62.3%; 53/85) went beyond the federal mandates than did those without (37.3%; 22/59). Types of additional individuals required to receive training included all students in selected programs (23.6%; 34/144), all students participating in externally funded research (12.5%; 18/144), all graduate students (11.1%; 16/144), all faculty/staff participating in externally funded research (9.7%; 14/144), all postdoctoral students or fellows (8.3%; 12/144), all doctoral-level students (4.9%; 7/144), all faculty/staff involved in human subjects research (4.9%; 7/144), and all faculty/staff involved in animal research (2.1%; 3/144).
Conclusions
More institutions with medical schools exceeded federal RCR training mandates than did those without. The authors encourage other institutions to expand their RCR requirements to promote research integrity.
C1 [Resnik, David B.] NIEHS, NIH, Eth Program, Res Triangle Pk, NC 27709 USA.
[Dinse, Gregg E.] NIEHS, NIH, Biostat Branch, Res Triangle Pk, NC 27709 USA.
RP Resnik, DB (reprint author), NIEHS, NIH, Eth Program, Box 12233,Mail Drop CU 03, Res Triangle Pk, NC 27709 USA.
EM resnikd@niehs.nih.gov
FU Intramural NIH HHS [ZIA ES102646-03]
NR 9
TC 11
Z9 11
U1 3
U2 17
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-2446
J9 ACAD MED
JI Acad. Med.
PD SEP
PY 2012
VL 87
IS 9
BP 1237
EP 1242
DI 10.1097/ACM.0b013e318260fe5c
PG 6
WC Education, Scientific Disciplines; Health Care Sciences & Services
SC Education & Educational Research; Health Care Sciences & Services
GA 001PT
UT WOS:000308473300023
PM 22836835
ER
PT J
AU Gutin, LS
Bakalov, VK
Rosing, DR
Arai, AE
Gharib, AM
Bondy, CA
AF Gutin, Liat S.
Bakalov, Vladimir K.
Rosing, Douglas R.
Arai, Andrew E.
Gharib, Ahmed M.
Bondy, Carolyn A.
TI N-terminal pro-brain natriuretic peptide levels and aortic diameters
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID GUANYLYL CYCLASE-A; TURNER-SYNDROME; B-TYPE; CARDIAC FIBROBLASTS;
HEART-FAILURE; MICE LACKING; DISSECTION; ATRIAL; RECEPTOR; BNP
AB Background Women with X-chromosome monosomy or Turner syndrome (TS) are at increased risk for aortic dilation and dissection. To better understand the pathology and develop tools to monitor the risk of aortic disease, we investigated N-terminal pro-brain natriuretic peptide (BNP) (NT-proBNP) levels in women with TS and healthy female controls.
Methods We evaluated NT-proBNP levels in women with karyotype-proven TS and healthy female volunteers in relation to ascending aortic diameter and descending aortic diameter measured by cardiovascular magnetic resonance imaging.
Results The NT-proBNP levels were strongly and positively correlated with ascending aortic diameter and descending aortic diameter in both cohorts. The TS group (n = 114, age 37.4 +/- 12 yr) had greater body surface area-indexed aortic diameters and higher NT-proBNP levels than the control group (n = 27, age 46.4 +/- 11 years): 88.3 +/- 62.7 versus 53.5 +/- 35 pg/mL, P = .0003. Within the TS group, NT-proBNP levels were higher in those with dilated ascending aorta (n = 42, 112.4 +/- 75.7 pg/mL) compared with those with normal aortic dimensions (n = 72, 74.2 +/- 49 pg/mL, P = .0014). Abnormally high NT-pro BNP levels were seen in 3 of 4 TS women who presented with previously undetected aortic aneurysm and/or dissection.
Conclusions The NT-proBNP levels are positively associated with aortic diameters in women with and without TS, suggesting a role for BNP in arterial wall homeostasis. Further study is necessary to determine whether NT-proBNP measurement may be used to monitor aortic diameter and/or detect aortic pathology in individuals at risk for aortic disease. (Am Heart J 2012;164:419-24.)
C1 [Gutin, Liat S.; Bakalov, Vladimir K.; Bondy, Carolyn A.] NICHHD, Sect Epigenet & Dev, Bethesda, MD 20892 USA.
[Rosing, Douglas R.; Arai, Andrew E.] NHLBI, Cardiovasc & Pulm Branch, Bethesda, MD 20892 USA.
[Gharib, Ahmed M.] NIDDK, Integrat Cardiovasc Imaging Sect, Bethesda, MD USA.
RP Bondy, CA (reprint author), NIH, CRC 1-3330,10 Ctr Dr, Bethesda, MD 20892 USA.
EM bondyc@mail.nih.gov
RI Gharib, Ahmed/O-2629-2016
OI Gharib, Ahmed/0000-0002-2476-481X
FU NIH
FX This work was supported by the intramural research program of the NIH.
No extramural funding was used to support this work.
NR 20
TC 4
Z9 4
U1 0
U2 3
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 2012
VL 164
IS 3
BP 419
EP 424
DI 10.1016/j.ahj.2012.06.021
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 004OD
UT WOS:000308690100020
PM 22980310
ER
PT J
AU Morishima, C
Shiffman, ML
Dienstag, JL
Lindsay, KL
Szabo, G
Everson, GT
Lok, AS
Di Bisceglie, AM
Ghany, MG
Naishadham, D
Morgan, TR
Wright, EC
AF Morishima, Chihiro
Shiffman, Mitchell L.
Dienstag, Jules L.
Lindsay, Karen L.
Szabo, Gyongyi
Everson, Gregory T.
Lok, Anna S.
Di Bisceglie, Adrian M.
Ghany, Marc G.
Naishadham, Deepa
Morgan, Timothy R.
Wright, Elizabeth C.
CA HALT-C Trial Grp
TI Reduction in Hepatic Inflammation Is Associated With Less Fibrosis
Progression and Fewer Clinical Outcomes in Advanced Hepatitis C
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
ID INTERFERON; THERAPY; PEGINTERFERON; RIBAVIRIN; METAANALYSIS; TRIALS;
VIRUS
AB OBJECTIVES: During the Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial, 3.5 years of maintenance peginterferon-alfa-2a therapy did not affect liver fibrosis progression or clinical outcomes among 1,050 previous interferon nonresponders with advanced fibrosis or cirrhosis. We investigated whether reduced hepatic inflammation was associated with clinical benefit in 834 patients with a baseline and follow-up biopsy 1.5 years after randomization to peginterferon or observation.
METHODS: Relationships between change in hepatic inflammation (Ishak hepatic activity index, (HAI)) and serum alanine aminotransferase level, fibrosis progression and clinical outcomes after randomization, and hepatitis C virus (HCV) RNA decline before and after randomization were evaluated. Histological change was defined as a >= 2-point difference in HAI or Ishak fibrosis score between biopsies.
RESULTS: Among 657 patients who received full-dose peginterferon/ribavirin "lead-in" therapy before randomization, year-1.5 HAI improvement was associated with lead-in HCV RNA suppression in both the randomized treated (P<0.0001) and control (P=0.0001) groups, even in the presence of recurrent viremia. This relationship persisted at year 3.5 in both the treated (P=0.001) and control (P=0.01) groups. Among 834 patients followed for a median of 6 years, fewer clinical outcomes occurred in patients with improved HAI at year 1.5 compared with those without such improvement in both the treated (P=0.03) and control (P=0.05) groups. Among patients with Ishak 3-4 fibrosis at baseline, those with improved HAI at year 1.5 had less fibrosis progression at year 1.5 in both the treated (P=0.0003) and control (P=0.02) groups.
CONCLUSIONS: Reduced hepatic inflammation (measured 1.5 and 3.5 years after randomization) was associated with profound virological suppression during lead-in treatment with full-dose peginterferon/ribavirin and with decreased fibrosis progression and clinical outcomes, independent of randomized treatment.
C1 [Morishima, Chihiro] Univ Washington, Dept Lab Med, Seattle, WA 98109 USA.
[Shiffman, Mitchell L.] Bon Secours Hlth Syst, Liver Inst Virginia, Newport News, VA USA.
[Dienstag, Jules L.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Lindsay, Karen L.] Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA 90033 USA.
[Szabo, Gyongyi] Univ Massachusetts, Sch Med, Dept Med, Div Gastroenterol,Hepatol & Liver Ctr, Worcester, MA USA.
[Everson, Gregory T.] Univ Colorado Denver, Sch Med, Sect Hepatol, Div Gastroenterol & Hepatol, Aurora, CO USA.
[Lok, Anna S.] Univ Michigan, Sch Med, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI USA.
[Di Bisceglie, Adrian M.] St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO USA.
[Ghany, Marc G.; Wright, Elizabeth C.] NIDDKD, Dept Hlth & Human Serv, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
[Naishadham, Deepa] New England Res Inst, Watertown, MA 02172 USA.
[Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA.
[Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA.
[Wright, Elizabeth C.] NIH, Dept Hlth & Human Serv, Off Director, Bethesda, MD 20892 USA.
RP Morishima, C (reprint author), Univ Washington, Dept Lab Med, Box 358050,850 Republican St, Seattle, WA 98109 USA.
EM chihiro@u.washington.edu
OI Yang, Shuman/0000-0002-9638-0890
FU National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK);
National Institute of Allergy and Infectious Diseases (NIAID); National
Cancer Institute; National Center for Minority Health and Health
Disparities; General Clinical Research Center and Clinical and
Translational Science Center from National Center for Research
Resources, National Institutes of Health (NIH); NIH, NIDDK; Genentech;
Tibotec, Inc.
FX This study was supported by the National Institute of Diabetes &
Digestive & Kidney Diseases (NIDDK contract numbers are listed below).
Additional support was provided by the National Institute of Allergy and
Infectious Diseases (NIAID); the National Cancer Institute; the National
Center for Minority Health and Health Disparities; by General Clinical
Research Center and Clinical and Translational Science Center grants
from the National Center for Research Resources, National Institutes of
Health (NIH grant numbers are listed below); and by the Intramural
Research Program of the NIH, NIDDK (M. G. Ghany). The content is solely
the responsibility of the authors and does not necessarily represent the
official views of the National Center for Research Resources or the
National Institutes of Health. Additional funding to conduct this study
was supplied by Hoffmann-La Roche, Inc. (now Genentech), through a
Cooperative Research and Development Agreement (CRADA) with the National
Institutes of Health.; Financial relationships of the authors with
Hoffmann-La Roche, Inc. (now Genentech), are as follows: M. L. Shiffman
is a consultant, on the speaker's bureau, and receives research support;
K. L. Lindsay was a consultant and received research support from
Hoffmann-La Roche, Inc. (now Genentech), during this study and is now an
employee of Tibotec, Inc. (a subsidiary of Johnson and Johnson),
Titusville, NJ; G. Szabo receives research support; G. T. Everson is a
consultant and receives research support; A. S. Lok is a consultant and
receives research support; A. M. Di Bisceglie is a consultant and
receives research support; and T. R. Morgan receives research support.
Authors with no financial relationships related to this project are: C.
Morishima, J. L. Dienstag, M. G. Ghany, D. Naishadham, and E. C. Wright.
NR 19
TC 5
Z9 5
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD SEP
PY 2012
VL 107
IS 9
BP 1388
EP 1398
DI 10.1038/ajg.2012.137
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 004NU
UT WOS:000308689200016
PM 22688849
ER
PT J
AU Tyler, CP
Paneth, N
Allred, EN
Hirtz, D
Kuban, K
McElrath, T
O'Shea, TM
Miller, C
Leviton, A
AF Tyler, Crystal P.
Paneth, Nigel
Allred, Elizabeth N.
Hirtz, Deborah
Kuban, Karl
McElrath, Thomas
O'Shea, T. Michael
Miller, Cindy
Leviton, Alan
CA ELGAN Study Investigators
TI Brain damage in preterm newborns and maternal medication: the ELGAN
Study
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE cerebral palsy; cerebral white matter damage; preterm
ID WHITE-MATTER DAMAGE; LOW-DOSE ASPIRIN; CEREBRAL-PALSY; CHILDREN BORN;
BIRTH-WEIGHT; 28TH WEEK; PREGNANCY; RATS; INHIBITION; DISORDERS
AB OBJECTIVE: We sought to evaluate the association between maternal medication use during pregnancy and cerebral white matter damage and cerebral palsy (CP) among very preterm infants.
STUDY DESIGN: This analysis of data from the Extremely Low Gestational Age Newborns (ELGAN) Study included 877 infants born <28 weeks' gestation. Mothers were interviewed, charts were reviewed, placentas were cultured and assessed histologically, and children were evaluated at 24 months corrected age. A diagnostic algorithm classified neurologic findings as quadriparetic CP, diparetic CP, hemiparetic CP, or no CP.
RESULTS: After adjustment for the potential confounding of disorders for which medications might have been indicated, the risk of quadri-paretic CP remained elevated among the infants of mothers who consumed aspirin (odds ratio [OR], 3.0; 95% confidence interval [CI], 1.36.9) and nonsteroidal antiinflammatory drugs (NSAIDs) (OR, 2.4; 95% CI, 1.04 -5.8). The risk of diparetic CP was also associated with maternal consumption of an NSAID, but only if the consumption was not approved by a physician (OR, 3.5; 95% CI 1.1-11.0).
CONCLUSION: The possibility that aspirin and NSAID use in pregnancy could lead to perinatal brain damage cannot be excluded.
C1 [Tyler, Crystal P.; Paneth, Nigel] Michigan State Univ, Coll Human Med, Dept Epidemiol, E Lansing, MI 48824 USA.
[Allred, Elizabeth N.; Leviton, Alan] Harvard Univ, Childrens Hosp Boston, Dept Neurol, Neuroepidemiol Unit, Boston, MA 02115 USA.
[Kuban, Karl] Boston Med Ctr, Dept Pediat, Div Pediat Neurol, Boston, MA USA.
[McElrath, Thomas] Brigham & Womens Hosp, Div Maternal Fetal Med, Boston, MA 02115 USA.
[Hirtz, Deborah] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA.
[O'Shea, T. Michael] Wake Forest Univ, Dept Neonatol, Winston Salem, NC 27109 USA.
[Miller, Cindy] Yale Univ, Sch Med, New Haven, CT USA.
RP Tyler, CP (reprint author), Ctr Dis Control & Prevent, Div Reprod Hlth, 4770 Buford Hwy,MS K-22, Atlanta, GA 30341 USA.
EM ctyler@cdc.gov
OI Kuban, Karl/0000-0001-5299-3567
FU National Institute of Neurological Diseases and Stroke
[5U01NS040069-05]; National Institute of Child Health and Human
Development [NIH-P30-HD-1865]
FX This work was supported by a cooperative agreement with the National
Institute of Neurological Diseases and Stroke (number 5U01NS040069-05)
and a program project grant from the National Institute of Child Health
and Human Development (number NIH-P30-HD-1865).
NR 36
TC 1
Z9 1
U1 1
U2 12
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD SEP
PY 2012
VL 207
IS 3
AR 192.e1
DI 10.1016/j.ajog.2012.06.059
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 003BL
UT WOS:000308583100023
PM 22939723
ER
PT J
AU Norton, JA
Fraker, DL
Alexander, HR
Jensen, RT
AF Norton, Jeffrey A.
Fraker, Douglas L.
Alexander, H. Richard
Jensen, Robert T.
TI Value of Surgery in Patients With Negative Imaging and Sporadic
Zollinger-Ellison Syndrome
SO ANNALS OF SURGERY
LA English
DT Article
DE gastrinoma; negative imaging; outcome; surgery
ID SOMATOSTATIN RECEPTOR SCINTIGRAPHY; ISLET CELL TUMORS; PANCREATIC
ENDOCRINE TUMORS; DUODENAL GASTRINOMAS; LONG-TERM; SURGICAL-MANAGEMENT;
NATURAL-HISTORY; SURVIVAL; CURE; LOCALIZATION
AB Objectives: To address the value of surgery in patients with sporadic Zollinger-Ellison syndrome (ZES) with negative imaging studies.
Background: Medical control of acid hypersecretion in patients with sporadic ZES is highly effective. This has led to these patients frequently not being sent to surgery, especially if preoperative imaging studies are negative, due, in large part, to existence of almost no data on the success of surgery in this group.
Methods: Fifty-eight prospectively studied patients with sporadic ZES (17% of total studied) had negative imaging studies, and their surgical outcome was compared with 117 patients with positive imaging results.
Results: Thirty-five patients had negative imaging studies in the presomatostatin receptor scintigraphy (SRS) era, and 23 patients in the post-SRS era. Patients with negative imaging studies had long disease histories before surgery [mean +/- SEM (from onset) = 7.9 +/- 1 [range, -0.25 to 35 years]) and 25% were followed for 2 or more years from diagnosis. At surgery, gastrinoma was found in 57 of 58 patients (98%). Tumors were small (mean = 0.8 cm, 60% < 1 cm). The most common primary sites were duodenal 64%, pancreatic 17%, and lymph node (10%). Fifty percent had a primary-only, 41% primary + lymph node, and 7% had liver metastases. Thirty-five of 58 patients (60%) were cured immediately postoperatively, and at last follow-up [mean = -9.4 years; range, 0.2-22 years], 27 patients (46%) remained cured. During follow-up, 3 patients died, each had liver metastases at surgery. In comparison to positive imaging patients, those with negative imaging studies had lower preoperative fasting gastrin levels; had a longer delay before surgery; more frequently had a small duodenal tumor; less frequently had a pancreatic tumor, multiple tumors, or developed a new lesion postoperatively; and had a longer survival.
Conclusions: Sporadic ZES patients with negative imaging studies are not rare even in the post-SRS period. An experienced surgeon can find gastrinoma in almost every patient (98%) and nearly one half (46%) are cured, a rate similar to patients with positive imaging findings. Because liver metastases were found in 7%, which may have been caused by a long delay in surgery and all the disease-related deaths occurred in this group, surgery should be routinely undertaken early in ZES patients despite negative imaging studies.
C1 [Norton, Jeffrey A.] Stanford Univ, Med Ctr, Dept Surg, Stanford, CA 94305 USA.
[Fraker, Douglas L.] Univ Penn, Philadelphia, PA 19104 USA.
[Alexander, H. Richard] Univ Maryland, College Pk, MD 20742 USA.
[Jensen, Robert T.] NIDDKD, NIH, Bethesda, MD 20892 USA.
RP Norton, JA (reprint author), Stanford Univ, Med Ctr, Dept Surg, Room H3591,300 Pasteur Dr, Stanford, CA 94305 USA.
EM janorton@stanford.edu
FU Intramural NIH HHS [Z99 DK999999, Z01 DK053200-17, ZIA DK053200-19]
NR 44
TC 10
Z9 10
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-4932
J9 ANN SURG
JI Ann. Surg.
PD SEP
PY 2012
VL 256
IS 3
BP 509
EP 517
DI 10.1097/SLA.0b013e318265f08d
PG 9
WC Surgery
SC Surgery
GA 004HB
UT WOS:000308670900023
PM 22868363
ER
PT J
AU Safronetz, D
Ebihara, H
Feldmann, H
Hooper, JW
AF Safronetz, David
Ebihara, Hideki
Feldmann, Heinz
Hooper, Jay W.
TI The Syrian hamster model of hantavirus pulmonary syndrome
SO ANTIVIRAL RESEARCH
LA English
DT Review
DE Hantavirus pulmonary syndrome; Andes virus; Bunyavirus; Hamster; Animal
model
ID HANTAAN VIRUS-INFECTION; SIN-NOMBRE-VIRUS; TO-PERSON TRANSMISSION; CREEK
CANAL VIRUS; M GENOME SEGMENT; ANDES VIRUS; CARDIOPULMONARY SYNDROME;
HEMORRHAGIC-FEVER; SUCKLING MICE; PUUMALA VIRUS
AB Hantavirus pulmonary syndrome (HPS) is a relatively rare, but frequently fatal disease associated with New World hantaviruses, most commonly Sin Nombre and Andes viruses in North and South America, respectively. It is characterized by fever and the sudden, rapid onset of severe respiratory distress and cardiogenic shock, which can be fatal in up to 50% of cases. Currently there are no approved antiviral therapies or vaccines for the treatment or prevention of HPS. A major obstacle in the development of effective medical countermeasures against highly pathogenic agents like the hantaviruses is recapitulating the human disease as closely as possible in an appropriate and reliable animal model. To date, the only animal model that resembles HPS in humans is the Syrian hamster model. Following infection with Andes virus, hamsters develop HPS-like disease which faithfully mimics the human condition with respect to incubation period and pathophysiology of disease. Perhaps most importantly, the sudden and rapid onset of severe respiratory distress observed in humans also occurs in hamsters. The last several years has seen an increase in studies utilizing the Andes virus hamster model which have provided unique insight into HPS pathogenesis as well as potential therapeutic and vaccine strategies to treat and prevent HPS. The purpose of this article is to review the current understanding of HPS disease progression in Syrian hamsters and discuss the suitability of utilizing this model to evaluate potential medical countermeasures against HPS. (c) 2012 Elsevier B.V. All rights reserved.
C1 [Safronetz, David; Ebihara, Hideki; Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT 59840 USA.
[Hooper, Jay W.] USA, Div Virol, Med Res Inst Infect Dis, Frederick, MD 21702 USA.
RP Safronetz, D (reprint author), NIAID, Virol Lab, Div Intramural Res, NIH, 903 S 4th St, Hamilton, MT 59840 USA.
EM safronetzd@niaid.nih.gov; jay.hooper@amedd.army.mil
OI Hooper, Jay/0000-0002-4475-0415
FU Intramural NIH HHS [Z99 AI999999]
NR 97
TC 26
Z9 26
U1 0
U2 17
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-3542
J9 ANTIVIR RES
JI Antiviral Res.
PD SEP
PY 2012
VL 95
IS 3
BP 282
EP 292
DI 10.1016/j.antivira1.2012.06.002
PG 11
WC Pharmacology & Pharmacy; Virology
SC Pharmacology & Pharmacy; Virology
GA 002FM
UT WOS:000308517500012
PM 22705798
ER
PT J
AU Yaffe, K
Falvey, C
Hamilton, N
Schwartz, AV
Simonsick, EM
Satterfield, S
Cauley, JA
Rosano, C
Launer, LJ
Strotmeyer, ES
Harris, TB
AF Yaffe, Kristine
Falvey, Cherie
Hamilton, Nathan
Schwartz, Ann V.
Simonsick, Eleanor M.
Satterfield, Suzanne
Cauley, Jane A.
Rosano, Caterina
Launer, Lenore J.
Strotmeyer, Elsa S.
Harris, Tamara B.
TI Diabetes, Glucose Control, and 9-Year Cognitive Decline Among Older
Adults Without Dementia
SO ARCHIVES OF NEUROLOGY
LA English
DT Article
ID MIDDLE-AGED ADULTS; MELLITUS; RISK; IMPAIRMENT; COHORT; ASSOCIATION;
DISEASE; WOMEN
AB Objectives: To determine if prevalent and incident diabetes mellitus (DM) increase risk of cognitive decline and if, among elderly adults with DM, poor glucose control is related to worse cognitive performance.
Design: Prospective cohort study.
Setting: Health, Aging, and Body Composition Study at 2 community clinics.
Participants: A total of 3069 elderly adults (mean age, 74.2 years; 42% black; 52% female).
Main Outcome Measures: Participants completed the Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) at baseline and selected intervals over 10 years. Diabetes mellitus status was determined at baseline and during follow-up visits. Glycosylated hemoglobin A(1c) level was measured at years 1 (baseline), 4, 6, and 10 from fasting whole blood.
Results: At baseline, 717 participants (23.4%) had prevalent DM and 2352 (76.6%) were without DM, 159 of whom developed incidentDMduring follow-up. Participants with prevalent DM had lower baseline test scores than participants without DM(3MS: 88.8 vs 90.9; DSST: 32.5 vs 36.3, respectively; t = 6.09; P =. 001 for both tests). Results from mixed-effects models showed a similar pattern for 9-year decline (3MS: -6.0-vs -4.5-point decline; t = 2.66; P =. 008; DSST: -7.9-vs -5.7-point decline; t = 3.69; P =. 001, respectively). Participants with incident DM tended to have baseline and 9-year decline scores between the other 2 groups but were not statistically different from the group without DM. Multivariate adjustment for demographics and medical comorbidities produced similar results. Among participants with prevalent DM, glycosylated hemoglobin A1c level was associated with lower average mean cognitive scores (3MS: F = 8.2; P for overall =. 003; DSST: F = 3.4; P for overall =. 04), even after multivariate adjustment.
Conclusion: Among well-functioning older adults, DM and poor glucose control among those with DM are associated with worse cognitive function and greater decline. This suggests that severity of DM may contribute to accelerated cognitive aging. Arch Neurol. 2012; 69(9): 1170-1175. Published online June 18, 2012. doi: 10.1001/archneurol.2012.1117
C1 [Yaffe, Kristine; Falvey, Cherie] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA.
[Yaffe, Kristine; Schwartz, Ann V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA.
[Yaffe, Kristine; Falvey, Cherie; Hamilton, Nathan] San Francisco VA Med Ctr, San Francisco, CA USA.
[Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
[Simonsick, Eleanor M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Launer, Lenore J.; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA.
[Cauley, Jane A.; Rosano, Caterina; Strotmeyer, Elsa S.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat, Box 181,4150 Clement St, San Francisco, CA 94121 USA.
EM kristine.yaffe@ucsf.edu
RI Strotmeyer, Elsa/F-3015-2014;
OI Rosano, Caterina/0000-0002-0909-1506; Strotmeyer,
Elsa/0000-0002-4093-6036; Rosano, Caterina/0000-0002-4271-6010; Cauley,
Jane A/0000-0003-0752-4408
FU NIH (NIA, National Institute of Diabetes and Digestive and Kidney
Diseases, and National Institute of Mental Health); Department of
Defense; American Health Assistance Foundation; Anonymous Foundation;
Alzheimer's Association; Amgen; Merck Serono; GlaxoSmithKline; NIH
(National Institute of Diabetes and Digestive and Kidney Diseases and
NIA); NIH/NIA; NIH/NIA Intramural Research Program; NIH; NIA
[N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050]; National
Institute of Nursing Research [R01-NR012459]; Intramural Research
Program of the NIH, NIA; American Health Assistance Foundation
[A201-0029]
FX Dr Yaffe has served on data safety monitoring boards for Pfizer Inc,
Medivation Inc, and the National Institutes of Health (NIH) (National
Institute of Mental Health and National Institute on Aging [NIA] trials)
and has received research support from the NIH (NIA, National Institute
of Diabetes and Digestive and Kidney Diseases, and National Institute of
Mental Health), the Department of Defense, American Health Assistance
Foundation, Anonymous Foundation, and the Alzheimer's Association. Dr
Schwartz serves on a scientific advisory board for GlaxoSmithKline; has
received speaker honoraria from Amgen and Merck Serono; has received
funding for travel from Amgen; and receives research support from Merck
Serono, GlaxoSmithKline, and the NIH (National Institute of Diabetes and
Digestive and Kidney Diseases and NIA). Dr Simonsick serves as an
associate editor for the Journal of Gerontology Medical Sciences. Dr
Satterfield receives research support from the NIH/NIA. Dr Cauley
receives research support from Novartis. Dr Launer receives research
support from the NIH/NIA Intramural Research Program. Dr Harris receives
research support from the NIH.; This work was supported by NIA contracts
N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106; NIA grant R01-AG028050;
and National Institute of Nursing Research grant R01-NR012459. This
research was supported in part by the Intramural Research Program of the
NIH, NIA, and grant A201-0029 from the American Health Assistance
Foundation. Dr Yaffe is supported in part by NIA grant K24AG031155.
NR 32
TC 89
Z9 93
U1 0
U2 13
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9942
J9 ARCH NEUROL-CHICAGO
JI Arch. Neurol.
PD SEP
PY 2012
VL 69
IS 9
BP 1170
EP 1175
DI 10.1001/archneurol.2012.1117
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 002UB
UT WOS:000308560600011
PM 22710333
ER
PT J
AU Grunwald, JE
Alexander, J
Ying, GS
Maguire, M
Daniel, E
Whittock-Martin, R
Parker, C
McWilliams, K
Lo, JC
Go, A
Townsend, R
Gadegbeku, CA
Lash, JP
Fink, JC
Rahman, M
Feldman, H
Kusek, JW
Xie, DW
Jaar, BG
AF Grunwald, Juan E.
Alexander, Judith
Ying, Gui-Shuang
Maguire, Maureen
Daniel, Ebenezer
Whittock-Martin, Revell
Parker, Candace
McWilliams, Kathleen
Lo, Joan C.
Go, Alan
Townsend, Raymond
Gadegbeku, Crystal A.
Lash, James P.
Fink, Jeffrey C.
Rahman, Mahboob
Feldman, Harold
Kusek, John W.
Xie, Dawei
Jaar, Bernard G.
CA CRIC Study Grp
TI Retinopathy and Chronic Kidney Disease in the Chronic Renal
Insufficiency Cohort (CRIC) Study
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID RETINAL MICROVASCULAR ABNORMALITIES; CARDIOVASCULAR RISK-FACTORS;
DIABETIC-RETINOPATHY; HYPERTENSIVE RETINOPATHY; ATHEROSCLEROSIS RISK;
VESSEL DIAMETERS; VASCULAR CALIBER; UNITED-STATES; MELLITUS;
ASSOCIATIONS
AB Objective: To investigate the association between retinopathy and chronic kidney disease.
Methods: In this observational, cross-sectional study, 2605 patients of the Chronic Renal Insufficiency Cohort (CRIC) study, a multicenter study of chronic kidney disease, were offered participation. Nonmydriatic fundus photographs of the disc and macula in both eyes were obtained in 1936 of these subjects. The photographs were reviewed in a masked fashion at a central photograph reading center using standard protocols. Presence and severity of retinopathy (diabetic, hypertensive, or other) and vessel diameter caliber were assessed by trained graders and a retinal specialist using protocols developed for large epidemiologic studies. Kidney function measurements and information on traditional and nontraditional risk factors for decreased kidney function were obtained from the CRIC study.
Results: Greater severity of retinopathy was associated with lower estimated glomerular filtration rate after adjustment for traditional and nontraditional risk factors. The presence of vascular abnormalities usually associated with hypertension was also associated with lower estimated glomerular filtration rate. We found no strong direct relationship between estimated glomerular filtration rate and average arteriolar or venular calibers.
Conclusions: Our findings show a strong association between severity of retinopathy and its features and level of kidney function after adjustment for traditional and nontraditional risk factors for chronic kidney disease, suggesting that retinovascular pathology reflects renal disease.
C1 [Grunwald, Juan E.; Alexander, Judith; Ying, Gui-Shuang; Maguire, Maureen; Daniel, Ebenezer; Parker, Candace; McWilliams, Kathleen; Townsend, Raymond; Feldman, Harold; Xie, Dawei] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Lo, Joan C.; Go, Alan] Kaiser Permanente No Calif, Oakland, CA USA.
[Gadegbeku, Crystal A.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Lash, James P.] Univ Illinois, Urbana, IL 61801 USA.
[Fink, Jeffrey C.] Univ Maryland, College Pk, MD 20742 USA.
[Kusek, John W.] NIDDKD, Bethesda, MD 20892 USA.
[Jaar, Bernard G.] Johns Hopkins Univ, Inst Med, Baltimore, MD USA.
[Rahman, Mahboob] Case Western Reserve Univ, Cleveland, OH 44106 USA.
RP Grunwald, JE (reprint author), Univ Penn, Sch Med, 51 N 39th St, Philadelphia, PA 19104 USA.
EM juangrun@mail.med.upenn.edu
OI Daniel, Ebenezer/0000-0002-2027-2316; Fink, Jeffrey/0000-0002-5622-5052
FU RTI International Amgen; National Institutes of Health [R01 DK 74151,
UL1 RR-024134, MO1 RR-16500, UL1 RR-024989, MO1 RR-000042, UL1
RR-024986, UL1 RR-029879, UL1 RR-024131]; Vivian S. Lasko Research Fund;
Nina C. Mackall Trust; Research to Prevent Blindness
FX The authors of this article have no relationship with companies that
have financial interest in the information contained in this article. Dr
Townsend is a consultant for Roche, GlaxoSmithKline, and NiCox. Dr
Feldman has a contract with RTI International Amgen.; This study was
funded by grants R01 DK 74151, UL1 RR-024134, MO1 RR-16500, UL1
RR-024989, MO1 RR-000042, UL1 RR-024986, UL1 RR-029879, and UL1
RR-024131 from the National Institutes of Health; the Vivian S. Lasko
Research Fund; the Nina C. Mackall Trust; and Research to Prevent
Blindness.
NR 33
TC 26
Z9 28
U1 0
U2 5
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9950
J9 ARCH OPHTHALMOL-CHIC
JI Arch. Ophthalmol.
PD SEP
PY 2012
VL 130
IS 9
BP 1136
EP 1144
PG 9
WC Ophthalmology
SC Ophthalmology
GA 002TQ
UT WOS:000308559200004
PM 22965589
ER
PT J
AU Mets, MB
Rich, WL
Lee, P
Schuman, JS
Wilson, D
Chew, E
Buckley, E
AF Mets, Marilyn B.
Rich, William L., III
Lee, Paul
Schuman, Joel S.
Wilson, David
Chew, Emily
Buckley, Edward
CA Council Amer Ophthalmological Soc
TI The Ophthalmic Practice of the Future
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID CARE; DIAGNOSIS; GLAUCOMA; QUALITY; SYSTEMS
AB How will the ophthalmologist of the future practice? What will be the effect of government policy? How will this impact the mix of health care providers responsible for the delivery of eye care to patients? What part will health record technology play in clinical practice? These topics were discussed at the Knapp Symposium of the 2011 Annual Meeting of the American Ophthalmological Society. The health care system within which ophthalmology will be practiced will be radically different, ruled by changes in collaboration, communication, and practice guidelines. Given the coming uncertainty of our professional lives, it is vital that we anticipate, contemplate, and plan for our futures. Arch Ophthalmol. 2012; 130(9):1195-1198
C1 [Mets, Marilyn B.] Northwestern Univ, Dept Ophthalmol, Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA.
[Rich, William L., III] Georgetown Univ, Dept Ophthalmol, Sch Med, Washington, DC USA.
[Lee, Paul; Buckley, Edward] Duke Univ, Ctr Eye, Dept Ophthalmol, Durham, NC 27710 USA.
[Schuman, Joel S.] Univ Pittsburgh, Dept Ophthalmol, Med Ctr, Pittsburgh, PA 15260 USA.
[Schuman, Joel S.] Univ Pittsburgh, Sch Med, Dept Ophthalmol, Pittsburgh, PA 15261 USA.
[Wilson, David] Univ Oregon, Dept Ophthalmol, Eugene, OR 97403 USA.
[Chew, Emily] NEI, Dept Ophthalmol, Bethesda, MD 20892 USA.
RP Mets, MB (reprint author), Northwestern Univ, Dept Ophthalmol, Lurie Childrens Hosp Chicago, 225 E Chicago Ave,Box 70, Chicago, IL 60611 USA.
EM mmets@luriechildrens.org
RI Schuman, Joel/K-7304-2012;
OI Schuman, Joel/0000-0002-8885-3766; Lee, Paul/0000-0002-3338-136X
FU Massachusetts Institute of Technology; Massachusetts Eye and Ear
Infirmary
FX Dr Schuman receives royalties for intellectual property licensed by
Massachusetts Institute of Technology and Massachusetts Eye and Ear
Infirmary to Carl Zeiss Meditec, Inc.
NR 21
TC 4
Z9 4
U1 0
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9950
J9 ARCH OPHTHALMOL-CHIC
JI Arch. Ophthalmol.
PD SEP
PY 2012
VL 130
IS 9
BP 1195
EP 1198
PG 4
WC Ophthalmology
SC Ophthalmology
GA 002TQ
UT WOS:000308559200012
PM 22965597
ER
PT J
AU Class, QA
D'Onofrio, BM
Singh, AL
Ganiban, JM
Spotts, EL
Lichtenstein, P
Reiss, D
Neiderhiser, JM
AF Class, Quetzal A.
D'Onofrio, Brian M.
Singh, Amber L.
Ganiban, Jody M.
Spotts, E. L.
Lichtenstein, Paul
Reiss, David
Neiderhiser, Jenae M.
TI Current Parental Depression and Offspring Perceived Self-Competence: A
Quasi-Experimental Examination
SO BEHAVIOR GENETICS
LA English
DT Article
DE Perceived self-competence; Perceived competence; Parental depression;
Quasi-experimental design; Children of Twins; Cousin comparison
ID INTERGENERATIONAL TRANSMISSION; ADOLESCENT DEPRESSION; MATERNAL
DEPRESSION; GENETIC PERSPECTIVE; EXTENDED CHILDREN; SYMPTOMS; BEHAVIOR;
TWINS; PSYCHOPATHOLOGY; ESTEEM
AB A genetically-informed, quasi-experimental design was used to examine the genetic and environmental processes underlying associations between current parental depressive symptoms and offspring perceived self-competence. Participants, drawn from a population-based Swedish sample, were 852 twin pairs and their male (52 %) and female offspring aged 15.7 +/- A 2.4 years. Parental depressive symptoms were measured using the Center for Epidemiological Studies Depression scale. Offspring perceived self-competence was measured using a modified Harter Perceived Competence Scale. Cousin comparisons and Children of Twins designs suggested that associations between maternal depressive symptoms and offspring perceived self-competence were due to shared genetic/environmental liability. The mechanism responsible for father-offspring associations, however, was independent of genetic factors and of extended family environmental factors, supporting a causal inference. Thus, mothers and fathers may impact offspring perceived self-competence via different mechanisms and unmeasured genetic and environmental selection factors must be considered when studying the intergenerational transmission of cognitive vulnerabilities for depression.
C1 [Class, Quetzal A.; D'Onofrio, Brian M.; Singh, Amber L.] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN 47405 USA.
[Ganiban, Jody M.; Neiderhiser, Jenae M.] George Washington Univ, Dept Psychol, Washington, DC 20052 USA.
[Spotts, E. L.] NIA, Div Behav & Social Res, Bethesda, MD 20892 USA.
[Lichtenstein, Paul] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Reiss, David] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA.
[Neiderhiser, Jenae M.] Penn State Univ, Dept Psychol, University Pk, PA 16802 USA.
RP Class, QA (reprint author), Indiana Univ, Dept Psychol & Brain Sci, 1101 E 10th St, Bloomington, IN 47405 USA.
EM qaclass@indiana.edu
OI lichtenstein, paul/0000-0003-3037-5287
FU NIMH [R01MH54601]; Indiana CTSI Career Development Award
[5TL1RR025759-03]; Kirschstein NRSA [MH 094011]; NICHD [HD HD061817]
FX The TOSS study was supported by NIMH (R01MH54601; PI: Reiss-Cohort 1;
PI: Neiderhiser-Cohort 2). QAC was supported by grants from Indiana CTSI
Career Development Award (5TL1RR025759-03, PI: Shekhar) and Kirschstein
NRSA (MH 094011). NICHD (HD HD061817) supported BMD.
NR 58
TC 5
Z9 5
U1 4
U2 14
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0001-8244
J9 BEHAV GENET
JI Behav. Genet.
PD SEP
PY 2012
VL 42
IS 5
BP 787
EP 797
DI 10.1007/s10519-012-9550-1
PG 11
WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary
SC Behavioral Sciences; Genetics & Heredity; Psychology
GA 006JV
UT WOS:000308816400008
PM 22692226
ER
PT J
AU Obican, SG
Jahnke, GD
Soldin, OP
Scialli, AR
AF Obican, Sarah G.
Jahnke, Gloria D.
Soldin, Offie P.
Scialli, Anthony R.
TI Teratology public affairs committee position paper: Iodine deficiency in
pregnancy
SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY
LA English
DT Article
DE iodine deficiency; pregnancy; iodine supplementation; thyroid hormones;
lactation; pregnancy complications; child development
ID MATERNAL THYROID-FUNCTION; UNITED-STATES; NEUROPSYCHOLOGICAL
DEVELOPMENT; INDUCED HYPERTHYROIDISM; CHILDREN BORN; IODIZED SALT;
SUPPLEMENTATION; WOMEN; EPIDEMIOLOGY; ASSOCIATION
AB Iodine deficiency is an important nutritional deficiency, with more than 2 billion people worldwide estimated to be at risk. The developing fetus and young children are particularly at risk. During pregnancy and lactation, iodine requirements increase, whether in iodine-poor or iodine-sufficient countries, making the mother and the developing fetus vulnerable. The American Thyroid Association (ATA) recommends 250 micrograms per day of iodine intake for pregnant and lactating women. The thyroid gland is able to adapt to the changes associated with pregnancy as long as sufficient iodine is present. Dietary intake is the sole source of iodine, which is essential to the synthesis of thyroid hormones. Iodine is found in multiple dietary sources including iodized salt, dairy products, seaweed, and fish. Prenatal vitamins containing iodine are a good source of iodine, but iodine content in multivitamin supplements is highly variable. Congenital hypothyroidism is associated with cretinism. Clinical hypothyroidism has been associated with increased risk of poor perinatal outcome including prematurity, low birth weight, miscarriage, preeclampsia, fetal death, and impaired fetal neurocognitive development. Subclinical hypothyroidism is also associated with poor pregnancy outcomes and potential fetal neurocognitive deficits, but the data are more variable than those for clinical hypothyroidism. We concur with the ATA recommendation that all pregnant and lactating women should ingest (through diet and supplements) 250 micrograms of iodine daily. To achieve this goal, we recommend that all pregnant and lactating women take daily iodine supplementation of 150 micrograms. Birth Defects Research (Part A) 94:677682, 2012. (c) 2012 Wiley Periodicals, Inc.
C1 [Obican, Sarah G.] George Washington Univ, Dept Obstet & Gynecol, Washington, DC USA.
[Jahnke, Gloria D.] Natl Inst Environm Hlth Sci, Div Natl Toxicol Program, Res Triangle Pk, NC USA.
[Soldin, Offie P.] Georgetown Univ, Med Ctr, Dept Oncol, PregnaTox, Washington, DC 20007 USA.
[Soldin, Offie P.] Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA.
[Soldin, Offie P.] Georgetown Univ, Med Ctr, Dept Obstet & Gynecol, Washington, DC 20007 USA.
[Soldin, Offie P.] Georgetown Univ, Med Ctr, Dept Pharmacol, Washington, DC 20007 USA.
[Soldin, Offie P.] Georgetown Univ, Med Ctr, Dept Physiol, Washington, DC 20007 USA.
[Scialli, Anthony R.] Tetra Tech Sci, Washington, DC USA.
RP Obican, SG (reprint author), 2150 Penn Ave NW, Washington, DC 20037 USA.
EM sarahobican@yahoo.com
FU NIA NIH HHS [R01 AG033867]
NR 45
TC 16
Z9 17
U1 0
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1542-0752
EI 1542-0760
J9 BIRTH DEFECTS RES A
JI Birth Defects Res. Part A-Clin. Mol. Teratol.
PD SEP
PY 2012
VL 94
IS 9
BP 677
EP 682
DI 10.1002/bdra.23051
PG 6
WC Developmental Biology; Toxicology
SC Developmental Biology; Toxicology
GA 001PY
UT WOS:000308473800001
PM 22903940
ER
PT J
AU Du, XL
Qian, XL
Papageorge, A
Schetter, AJ
Vass, WC
Liu, X
Braverman, R
Robles, AI
Lowy, DR
AF Du, Xiaoli
Qian, Xiaolan
Papageorge, Alex
Schetter, Aaron J.
Vass, William C.
Liu, Xi
Braverman, Richard
Robles, Ana I.
Lowy, Douglas R.
TI Functional Interaction of Tumor Suppressor DLC1 and Caveolin-1 in Cancer
Cells
SO CANCER RESEARCH
LA English
DT Article
ID GTPASE-ACTIVATING PROTEIN; LYMPH-NODE METASTASIS; START DOMAIN PROTEIN;
LUNG-CANCER; HEPATOCELLULAR-CARCINOMA; BREAST-CANCER; RHO-GTPASES; SH2
DOMAIN; EXPRESSION; LIVER
AB Deleted in liver cancer 1 (DLC1), a tumor suppressor gene frequently inactivated in non-small cell lung cancer (NSCLC) and other malignancies, encodes a multidomain protein with a RhoGTPase-activating (RhoGAP) domain and a StAR-related lipid transfer (START) domain. However, no interacting macromolecule has been mapped to the DLC1 START domain. Caveolin-1 (CAV-1) functions as a tumor suppressor in most contexts and forms a complex with DLC1. Here, we have mapped the region of DLC1 required for interaction with CAV-1 to the DLC1 START domain. Mutation of the DLC1 START domain disrupted the interaction and colocalization with CAV-1. Moreover, DLC1 with a START domain mutation failed to suppress neoplastic growth, although it negatively regulated active Rho. CAV-1 and DLC1 expression levels were correlated in two public datasets of NSCLC lines and in two independent publicly available mRNA expression datasets of NSCLC tumors. Clinically, low DLC1 expression predicted a poor clinical outcome in patients with lung cancer. Together, our findings indicate that complex formation between the DLC1 START domain and CAV-1 contributes to DLC1 tumor suppression via a RhoGAP-independent mechanism, and suggest that DLC1 inactivation probably contributes to cancer progression. Cancer Res; 72(17); 4405-16. (C) 2012 AACR.
C1 [Du, Xiaoli; Qian, Xiaolan; Papageorge, Alex; Vass, William C.; Liu, Xi; Braverman, Richard; Lowy, Douglas R.] NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Schetter, Aaron J.; Robles, Ana I.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Lowy, DR (reprint author), NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bldg 37,Room4106, Bethesda, MD 20892 USA.
EM lowyd@mail.nih.gov
FU NIH, National Cancer Institute, and Center for Cancer Research
FX This research was supported by the Intramural Research Program, NIH,
National Cancer Institute, and Center for Cancer Research.
NR 50
TC 16
Z9 18
U1 1
U2 9
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD SEP 1
PY 2012
VL 72
IS 17
BP 4405
EP 4416
DI 10.1158/0008-5472.CAN-12-0777
PG 12
WC Oncology
SC Oncology
GA 002VS
UT WOS:000308565600014
PM 22693251
ER
PT J
AU Falade-Nwulia, OO
Dhaliwal, G
Schreiber, MP
Saint, S
Shorr, AF
AF Falade-Nwulia, Oluwaseun O.
Dhaliwal, Gurpreet
Schreiber, Matthew P.
Saint, Sanjay
Shorr, Andrew F.
TI A 36-Year-Old Haitian Man With Coma, Acute Kidney Injury, Lactic
Acidosis, and Respiratory Failure
SO CHEST
LA English
DT Editorial Material
ID FALCIPARUM-MALARIA; UNITED-STATES
C1 [Falade-Nwulia, Oluwaseun O.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
Johns Hopkins Sch Med, Div Infect Dis, Baltimore, MD USA.
Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA.
[Dhaliwal, Gurpreet] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA.
[Schreiber, Matthew P.; Shorr, Andrew F.] Washington Hosp Ctr, Div Pulm & Crit Care Med, Washington, DC 20010 USA.
Georgetown Univ, Washington, DC USA.
[Saint, Sanjay] Univ Michigan, Ann Arbor VA Med Ctr, Ann Arbor, MI 48109 USA.
[Saint, Sanjay] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
RP Falade-Nwulia, OO (reprint author), NIH, Dept Crit Care Med, 10 Ctr Dr,Rm 2C145, Bethesda, MD 20892 USA.
EM ofalade1@jhmi.edu
NR 10
TC 1
Z9 2
U1 1
U2 1
PU AMER COLL CHEST PHYSICIANS
PI NORTHBROOK
PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA
SN 0012-3692
J9 CHEST
JI Chest
PD SEP
PY 2012
VL 142
IS 3
BP 798
EP 801
DI 10.1378/chest.11-3209
PG 4
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 003PE
UT WOS:000308623000037
PM 22948586
ER
PT J
AU Wagner, L
Verma, A
Meade, BD
Reiter, K
Narum, DL
Brady, RA
Little, SF
Burns, DL
AF Wagner, Leslie
Verma, Anita
Meade, Bruce D.
Reiter, Karine
Narum, David L.
Brady, Rebecca A.
Little, Stephen F.
Burns, Drusilla L.
TI Structural and Immunological Analysis of Anthrax Recombinant Protective
Antigen Adsorbed to Aluminum Hydroxide Adjuvant
SO CLINICAL AND VACCINE IMMUNOLOGY
LA English
DT Article
ID LETHAL TOXIN NEUTRALIZATION; BACILLUS-ANTHRACIS; MONOCLONAL-ANTIBODIES;
SALT ADJUVANTS; GUINEA-PIGS; VACCINE; PROTEIN; STABILITY; RECEPTOR;
BINDING
AB New anthrax vaccines currently under development are based on recombinant protective antigen (rPA) and formulated with aluminum adjuvant. Because long-term stability is a desired characteristic of these vaccines, an understanding of the effects of adsorption to aluminum adjuvants on the structure of rPA is important. Using both biophysical and immunological techniques, we compared the structure and immunogenicity of freshly prepared rPA-Alhydrogel formulations to that of formulations stored for 3 weeks at either room temperature or 37 degrees C in order to assess the changes in rPA structure that might occur upon long-term storage on aluminum adjuvant. Intrinsic fluorescence emission spectra of tryptophan residues indicated that some tertiary structure alterations of rPA occurred during storage on Alhydrogel. Using anti-PA monoclonal antibodies to probe specific regions of the adsorbed rPA molecule, we found that two monoclonal antibodies that recognize epitopes located in domain 1 of PA exhibited greater reactivity to the stored formulations than to freshly prepared formulations. Immunogenicity of rPA-Alhydrogel formulations in mice was assessed by measuring the induction of toxin-neutralizing antibodies, as well as antibodies reactive to 12-mer peptides spanning the length of PA. Mice immunized with freshly prepared formulations developed significantly higher toxin-neutralizing antibody titers than mice immunized with the stored preparations. In contrast, sera from mice immunized with stored preparations exhibited increased reactivity to nine 12-mer peptides corresponding to sequences located throughout the rPA molecule. These results demonstrate that storage of rPA-Alhydrogel formulations can lead to structural alteration of the protein and loss of the ability to elicit toxin-neutralizing antibodies.
C1 [Wagner, Leslie; Verma, Anita; Brady, Rebecca A.; Burns, Drusilla L.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
[Meade, Bruce D.] Meade Biol, Hillsborough, NC USA.
[Reiter, Karine; Narum, David L.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD USA.
[Little, Stephen F.] USA, Med Res Inst Infect Dis, Frederick, MD USA.
RP Burns, DL (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
EM drusilla.burns@fda.hhs.gov
FU National Institute of Allergy and Infectious Diseases, NIH; Center for
Biologics Evaluation and Research, Food and Drug Administration
FX This work was supported by the Intramural Research Programs of the
National Institute of Allergy and Infectious Diseases, NIH, and the
Center for Biologics Evaluation and Research, Food and Drug
Administration. The following reagents were obtained from the NIH
Biodefense and Emerging Infections Research Resources Repository, NIAID,
NIH: anthrax PA, recombinant from B. anthracis, NR-164; anthrax LF,
recombinant from B. anthracis, NR-142; J774A. 1 monocyte/macrophage
(mouse) working cell bank, NR-28; and rabbit anti-PA reference serum
pool, NR-3839.
NR 39
TC 17
Z9 17
U1 0
U2 16
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 1556-6811
J9 CLIN VACCINE IMMUNOL
JI Clin. Vaccine Immunol.
PD SEP
PY 2012
VL 19
IS 9
BP 1465
EP 1473
DI 10.1128/CVI.00174-12
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 002AX
UT WOS:000308503400017
PM 22815152
ER
PT J
AU Kuban, W
Vaisman, A
McDonald, JP
Karata, K
Yang, W
Goodman, MF
Woodgate, R
AF Kuban, Wojciech
Vaisman, Alexandra
McDonald, John P.
Karata, Kiyonobu
Yang, Wei
Goodman, Myron F.
Woodgate, Roger
TI Escherichia coli UmuC active site mutants: Effects on translesion DNA
synthesis, mutagenesis and cell survival
SO DNA REPAIR
LA English
DT Article
DE SOS mutagenesis; pol V; UV-mutagenesis; Ribonucleotide incorporation
ID UMUD'C PROTEIN COMPLEX; SOS MUTAGENESIS; POLYMERASE-ETA; IN-VITRO;
POL-V; RECA PROTEIN; GENE ENCODES; CLEAVAGE; RECOMBINATION; UV
AB Escherichia coli polymerase V (pol V/UmuD(2)'C) is a low-fidelity DNA polymerase that has recently been shown to avidly incorporate ribonucleotides (rNTPs) into undamaged DNA. The fidelity and sugar selectivity of pot V can be modified by missense mutations around the "steric gate" of UmuC. Here, we analyze the ability of three steric gate mutants of UmuC to facilitate translesion DNA synthesis (TLS) of a cyclobutane pyrimidine dimer (CPD) in vitro, and to promote UV-induced mutagenesis and cell survival in vivo. The pol V (UmuC_F10L) mutant discriminates against rNTP and incorrect dNTP incorporation much better than wild-type pol V and although exhibiting a reduced ability to bypass a CPD in vitro, does so with high-fidelity and consequently produces minimal UV-induced mutagenesis in vivo. In contrast, pol V (UmuC_Y11A) readily misincorporates both rNTPs and dNTPs during efficient TLS of the CPD in vitro. However, cells expressing umuD'C(Y11A) were considerably more UV-sensitive and exhibited lower levels of UV-induced mutagenesis than cells expressing wild-type umuD'C or umuD'C(Y11F). We propose that the increased UV-sensitivity and reduced UV-mutability of umuD'C(Y11A) is due to excessive incorporation of rNTPs during TLS that are subsequently targeted for repair, rather than an inability to traverse UV-induced lesions. Published by Elsevier B.V.
C1 [Kuban, Wojciech; Vaisman, Alexandra; McDonald, John P.; Woodgate, Roger] NICHHD, Lab Genom Integr, NIH, Bethesda, MD 20892 USA.
[Karata, Kiyonobu] Chiba Univ, Grad Sch Pharmacol Sci, Chiba 2608675, Japan.
[Yang, Wei] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Goodman, Myron F.] Univ So Calif, Dept Biol Sci & Chem, Los Angeles, CA 90089 USA.
RP Woodgate, R (reprint author), 9800 Med Ctr Dr,Bldg C,Rm 320, Bethesda, MD 20892 USA.
EM woodgate@nih.gov
RI Yang, Wei/D-4926-2011; Vaisman, Alexandra/C-3766-2013
OI Yang, Wei/0000-0002-3591-2195; Vaisman, Alexandra/0000-0002-2521-1467
FU National Institute of Child Health and Human Development/National
Institutes of Health Intramural Research Program; National Institute of
Diabetes and Digestive and Kidney Diseases/National Institutes of Health
Intramural Research Program; Special Coordination Funds for Promoting
Science and Technology of the Japanese Ministry of Education, Culture,
Sports, Science and Technology; National Institutes of Health [GM21422,
ESO12259]
FX This work was supported in part by the National Institute of Child
Health and Human Development/National Institutes of Health Intramural
Research Program to RW; the National Institute of Diabetes and Digestive
and Kidney Diseases/National Institutes of Health Intramural Research
Program to WY; the Special Coordination Funds for Promoting Science and
Technology of the Japanese Ministry of Education, Culture, Sports,
Science and Technology to KK; and National Institutes of Health
[GM21422, ESO12259] to MFG.
NR 54
TC 12
Z9 12
U1 0
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
EI 1568-7856
J9 DNA REPAIR
JI DNA Repair
PD SEP 1
PY 2012
VL 11
IS 9
BP 726
EP 732
DI 10.1016/j.dnarep.2012.06.005
PG 7
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA 002HW
UT WOS:000308523700002
PM 22784977
ER
PT J
AU Zhao, BZ
Summers, FA
Mason, RP
AF Zhao, Baozhong
Summers, Fiona A.
Mason, Ronald P.
TI Photooxidation of Amplex red to resorufin: Implications of exposing the
Amplex red assay to light
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Amplex Red; Resorufin; Photooxidation; Free radical; Superoxide;
Hydrogen peroxide
ID HYPOXIC PULMONARY VASOCONSTRICTION; ELECTRON-SPIN-RESONANCE; INDUCED
EGF-RECEPTOR; SMOOTH-MUSCLE-CELLS; HYDROGEN-PEROXIDE; REACTIVE OXYGEN;
OXIDATIVE STRESS; MITOCHONDRIA; FLUORESCENT; H2O2
AB The Amplex Red assay, a fluorescent assay for the detection of H2O2, relies on the reaction of H2O2 and colorless, nonfluorescent Amplex Red with a 1:1 stoichiometry to form colored, fluorescent resorufin, catalyzed by horseradish peroxidase (HRP). We have found that resorufin is artifactually formed when Amplex Red is exposed to light. In the absence of H2O2 and HRP, the absorption and fluorescence spectra of Amplex Red changed during exposure to ambient room light or instrumental excitation light, clearly indicating that the fluorescent product resorufin had formed. This photochemistry was initiated by trace amounts of resorufin that are present in Amplex Red stock solutions. ESR spin-trapping studies demonstrated that superoxide radical was an intermediate in this process. Oxygen consumption measurements further confirmed that superoxide and H2O2 were artifactually produced by the photooxidation of Amplex Red. The artifactual formation of resorufin was also significantly increased by the presence of superoxide dismutase or HRP. This photooxidation process will result in a less sensitive assay for H2O2 under ambient light exposure and potentially invalid measurements under high energy exposure such as UVA irradiation. In general, precautions should be taken to minimize exposure to light during measurement of oxidative stress with Amplex Red. Published by Elsevier Inc.
C1 [Zhao, Baozhong; Summers, Fiona A.; Mason, Ronald P.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
RP Summers, FA (reprint author), NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
EM summersfa@niehs.nih.gov
RI Zhao, Baozhong/B-5865-2011
FU Intramural Research Program of the National Institutes of Health;
National Institute of Environmental Health Sciences [Z01 ES050139-13]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health and the National Institute of
Environmental Health Sciences (Z01 ES050139-13). The authors are
indebted to Mrs. Mary Mason and Dr. Ann Motten for their critical
reading of the manuscript.
NR 26
TC 37
Z9 37
U1 6
U2 52
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD SEP 1
PY 2012
VL 53
IS 5
BP 1080
EP 1087
DI 10.1016/j.freeradbiomed.2012.06.034
PG 8
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 003PV
UT WOS:000308624700007
PM 22765927
ER
PT J
AU Mukhopadhyay, P
Horvath, B
Zsengeller, Z
Batkai, S
Cao, ZX
Kechrid, M
Holovac, E
Erdelyi, K
Tanchian, G
Liaudet, L
Stillman, IE
Joseph, J
Kalyanaraman, B
Pacher, P
AF Mukhopadhyay, Partha
Horvath, Bela
Zsengeller, Zsuzsanna
Batkai, Sandor
Cao, Zongxian
Kechrid, Malek
Holovac, Eileen
Erdelyi, Katalin
Tanchian, Galin
Liaudet, Lucas
Stillman, Isaac E.
Joseph, Joy
Kalyanaraman, Balaraman
Pacher, Pal
TI Mitochondrial reactive oxygen species generation triggers inflammatory
response and tissue injury associated with hepatic ischemia-reperfusion:
Therapeutic potential of mitochondrially targeted antioxidants
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Ischemia-reperfusion; Antioxidants; Oxidative stress; Reactive oxygen
and nitrogen species; Free radicals
ID LIVER ISCHEMIA; NITRIC-OXIDE; IN-VIVO; OXIDATIVE STRESS; CELL-DEATH;
ISCHEMIA/REPERFUSION INJURY; HMGB1 RELEASE; PEROXYNITRITE; SUPEROXIDE;
APOPTOSIS
AB Mitochondrial reactive oxygen species generation has been implicated in the pathophysiology of ischemia-reperfusion (I/R) injury; however, its exact role and its spatial-temporal relationship with inflammation are elusive. Herein we explore the spatial-temporal relationship of oxidative/nitrative stress and inflammatory response during the course of hepatic I/R and the possible therapeutic potential of mitochondrial-targeted antioxidants, using a mouse model of segmental hepatic ischemia-reperfusion injury. Hepatic I/R was characterized by early (at 2 h of reperfusion) mitochondrial injury, decreased complex I activity, increased oxidant generation in the liver or liver mitochondria, and profound hepatocellular injury/dysfunction with acute proinflammatory response (TNF-alpha, MIP-1 alpha/CCL3, MIP-2/CXCL2) without inflammatory cell infiltration, followed by marked neutrophil infiltration and a more pronounced secondary wave of oxidative/nitrative stress in the liver (starting from 6 h of reperfusion and peaking at 24 h). Mitochondrially targeted antioxidants, MitoQ or Mito-CP, dose-dependently attenuated I/R-induced liver dysfunction, the early and delayed oxidative and nitrative stress response (HNE/carbonyl adducts, malondialdehyde, 8-OHdG, and 3-nitrotyrosine formation), and mitochondrial and histopathological injury/dysfunction, as well as delayed inflammatory cell infiltration and cell death. Mitochondrially generated oxidants play a central role in triggering the deleterious cascade of events associated with hepatic I/R, which may be targeted by novel antioxidants for therapeutic advantage. Published by Elsevier Inc.
C1 [Mukhopadhyay, Partha; Horvath, Bela; Batkai, Sandor; Cao, Zongxian; Kechrid, Malek; Holovac, Eileen; Erdelyi, Katalin; Tanchian, Galin; Pacher, Pal] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA.
[Joseph, Joy; Kalyanaraman, Balaraman] Med Coll Wisconsin, Free Rad Res Ctr, Milwaukee, WI 53226 USA.
[Zsengeller, Zsuzsanna; Stillman, Isaac E.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA.
[Zsengeller, Zsuzsanna; Stillman, Isaac E.] Harvard Univ, Sch Med, Boston, MA 02215 USA.
[Liaudet, Lucas] Univ Hosp Ctr, Dept Intens Care Med, CH-1011 Lausanne, Switzerland.
[Liaudet, Lucas] Fac Biol & Med, CH-1011 Lausanne, Switzerland.
[Horvath, Bela] Semmelweis Univ, Inst Human Physiol & Clin Expt Res, H-1085 Budapest, Hungary.
RP Pacher, P (reprint author), NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA.
EM pacher@mail.nih.gov
RI Horvath, Bela/A-7368-2009; Pacher, Pal/B-6378-2008; Batkai,
Sandor/H-7983-2014; Liaudet, Lucas/E-1322-2017;
OI Pacher, Pal/0000-0001-7036-8108; Liaudet, Lucas/0000-0003-2670-4930;
Mukhopadhyay, Partha/0000-0002-1178-1274
FU Intramural Research Program of the NIAAA/NIH; Hungarian Research Council
Scientific Research Fund Fellowship [OTKA-NKTH-EU MB08-80238]
FX This study was supported by the Intramural Research Program of the
NIAAA/NIH (to P.P.). Dr. Bela Horvath is the recipient of a Hungarian
Research Council Scientific Research Fund Fellowship (OTKA-NKTH-EU
MB08-80238). The authors are indebted to Dr. George Kunos, the
Scientific Director of the NIAAA/NIH, for providing key resources and
support.
NR 46
TC 41
Z9 43
U1 0
U2 19
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD SEP 1
PY 2012
VL 53
IS 5
BP 1123
EP 1138
DI 10.1016/j.freeradbiomed.2012.05.036
PG 16
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 003PV
UT WOS:000308624700011
PM 22683818
ER
PT J
AU Goodman, MS
Gaskin, DJ
Si, XM
Stafford, JD
Lachance, C
Kaphingst, KA
AF Goodman, Melody S.
Gaskin, Darrell J.
Si, Xuemei
Stafford, Jewel D.
Lachance, Christina
Kaphingst, Kimberly A.
TI Self-reported segregation experience throughout the life course and its
association with adequate health literacy
SO HEALTH & PLACE
LA English
DT Article
DE Racial composition; Residential segregation; Health literacy; Community
health center
ID RACIAL RESIDENTIAL SEGREGATION; NEWEST VITAL SIGN; INFANT-MORTALITY;
AFRICAN-AMERICAN; UNITED-STATES; PERCEIVED DISCRIMINATION; PHYSICIAN
PARTICIPATION; METROPOLITAN-AREAS; HOSPITAL ADMISSION; CHRONIC DISEASE
AB Residential segregation has been shown to be associated with health outcomes and health care utilization. We examined the association between racial composition of five physical environments throughout the life course and adequate health literacy among 836 community health center patients in Suffolk County, NY. Respondents who attended a mostly White junior high school or currently lived in a mostly White neighborhood were more likely to have adequate health literacy compared to those educated or living in predominantly minority or diverse environments. This association was independent of the respondent's race, ethnicity, age, education, and country of birth. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Goodman, Melody S.; Si, Xuemei; Stafford, Jewel D.; Kaphingst, Kimberly A.] Washington Univ, Sch Med, St Louis, MO 63130 USA.
[Gaskin, Darrell J.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Lachance, Christina] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Goodman, MS (reprint author), Washington Univ, Sch Med, St Louis, MO 63130 USA.
EM goodmanm@wustl.edu
RI Goodman, Melody/F-6768-2011
OI Goodman, Melody/0000-0001-8932-624X
FU Intramural Research Program of the National Human Genome Research
Institute (NHGRI), National Institutes of Health; Intramural NHGRI
funds; Barnes-Jewish Hospital Foundation
FX This research was supported by the Intramural Research Program of the
National Human Genome Research Institute (NHGRI), National Institutes of
Health. Intramural NHGRI funds provided funding to support the research
study and salary support. Drs. Goodman and Kaphingst were also supported
by funding from the Barnes-Jewish Hospital Foundation. The NHGRI and the
Barnes-Jewish Hospital Foundation have no financial interests in this
research.
NR 67
TC 3
Z9 3
U1 2
U2 9
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1353-8292
J9 HEALTH PLACE
JI Health Place
PD SEP
PY 2012
VL 18
IS 5
BP 1115
EP 1121
DI 10.1016/j.healthplace.2012.04.010
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 991VH
UT WOS:000307730300023
PM 22658579
ER
PT J
AU Stratakis, CA
AF Stratakis, C. A.
TI Cyclic AMP, Protein Kinase A, and Phosphodiesterases: Proceedings of an
International Workshop
SO HORMONE AND METABOLIC RESEARCH
LA English
DT Editorial Material
ID REGULATORY SUBUNIT; CARNEY COMPLEX; ADRENAL-HYPERPLASIA; NUCLEOTIDE
PHOSPHODIESTERASES; ADRENOCORTICAL TUMORS; PRKAR1A MUTATIONS; 11A
PDE11A; CAMP; GENE; ALPHA
AB Cyclic nucleotides cAMP and cGMP are part of almost all major cellular signaling pathways. Phosphodiesterases (PDEs) are enzymes that regulate the intracellular levels of cAMP and cGMP. Protein kinase A or cAMP-dependent protein kinase mediates most cAMP effects in the cell. Over the last 25 years, various components of this group of molecules have been involved in human diseases, both genetic and acquired. Lately, the PDEs attract more attention. The pharmacological exploitation of the PDE's ability to regulate cGMP and cAMP, and through them, a variety of signaling pathways, has led to a number of new drugs for diverse applications from the treatment of erectile dysfunction to heart failure, asthma, and chronic obstructive pulmonary disease. We present the abstracts (available online) and selected articles from the proceedings of a meeting that took place at the National Institutes of Health (NIH), Bethesda, MD, June 8-10, 2011.
C1 [Stratakis, C. A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol Genet, NIH, Bethesda, MD USA.
RP Stratakis, CA (reprint author), NICHD, Natl Inst Child Hlth & Human Dev NICHD, Sect Endocrinol & Genet SEGEN, PDEGEN,NIH,CRC, Bldg 10,Room 1-3330 10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA.
EM stratakc@mail.nih.gov
FU Intramural NIH HHS [ZIA HD000642-12]
NR 44
TC 4
Z9 4
U1 0
U2 2
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0018-5043
J9 HORM METAB RES
JI Horm. Metab. Res.
PD SEP
PY 2012
VL 44
IS 10
BP 713
EP 715
DI 10.1055/s-0031-1301327
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 007CI
UT WOS:000308866000001
PM 22951901
ER
PT J
AU Hussain, MA
Stratakis, C
Kirschner, L
AF Hussain, M. A.
Stratakis, C.
Kirschner, L.
TI Prkar1a in the Regulation of Insulin Secretion
SO HORMONE AND METABOLIC RESEARCH
LA English
DT Review
DE type 2 diabetes; Prkar1a; insulin secretion
ID DEPENDENT DIABETES-MELLITUS; O-GLCNACYLATION; SNARE COMPLEX; GLUCOSE;
PHOSPHORYLATION; 1ST-PHASE; SNAPIN
AB The incidence of type 2 diabetes mellitus (T2DM) is rapidly increasing worldwide with significant consequences on individual quality of life as well as economic burden on states' healthcare costs. While origins of the pathogenesis of T2DM are poorly understood, an early defect in glucose-stimulated insulin secretion (GSIS) from pancreatic beta-cells is considered a hallmark of T2DM [1]. Upon a glucose stimulus, insulin is secreted in a biphasic manner with an early first-phase burst of insulin, which is followed by a second, more sustained phase of insulin output [2]. First phase insulin secretion is diminished early in T2DM as well is in subjects who are at risk of developing T2DM [3-6].
An effective treatment of T2DM with incretin hormone glucagon-like peptide-1 (GLP-1) or its long acting peptide analogue exendin-4 (E4), restores first-phase and augments second-phase glucose stimulated insulin secretion. This effect of incretin action occurs within minutes of GLP-1/E4 infusion in T2DM humans. An additional important consideration is that incretin hormones augment GSIS only above a certain glucose threshold, which is slightly above the normal glucose range. This ensures that incretin hormones stimulate GSIS only when glucose levels are high, while they are ineffective when insulin levels are below a certain threshold [7, 8]. Activation of the GLP-1 receptor, which is highly expressed on pancreatic beta-cells, stimulates 2 distinct intracellular signaling pathways: a) the cAMP-protein kinase A branch and b) the cAMP-EPAC2 (EPAC = exchange protein activated by cAMP) branch. While the EPAC2 branch is considered to mediate GLP-1 effects on first-phase GSIS, the PKA branch is necessary for the former branch to be active [9, 10]. However, how these 2 branches interplay and converge and how their effects on insulin secretion and insulin vesicle exocytosis are coordinated is poorly understood. Thus, at the outset of our studies we have a poorly understood intracellular interplay of cAMP-dependent signaling pathways, which when stimulated - restore glucose-dependent first phase and augment second phase insulin secretion in the ailing beta-cells of T2DM.
C1 [Hussain, M. A.] Johns Hopkins Univ, Sch Med, Dept Pediat Med & Biol Chem, Baltimore, MD 21287 USA.
[Stratakis, C.] NICHD, Betheseda, MD USA.
[Kirschner, L.] Ohio State Univ, Dept Med, Columbus, OH 43210 USA.
RP Hussain, MA (reprint author), Johns Hopkins Univ, Sch Med, Dept Pediat Med & Biol Chem, 600 N Wolfe St, Baltimore, MD 21287 USA.
EM mhussai4@jhmi.edu
FU Endocrine Society Student Research Fellowship; Eunice Kennedy Shriver
National Institutes of Child Health and Human Development Intramural
Program (CAS); National Institutes of Health (NIH) [CA112268, DK81472,
DK63349, DK84948, DK79637]
FX Supported by an Endocrine Society Student Research Fellowship (MAH),
Eunice Kennedy Shriver National Institutes of Child Health and Human
Development Intramural Program (CAS), National Institutes of Health
(NIH) CA112268 (LSK), DK81472, DK63349, DK84948 and DK79637 (MAH).
NR 19
TC 4
Z9 4
U1 2
U2 8
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0018-5043
J9 HORM METAB RES
JI Horm. Metab. Res.
PD SEP
PY 2012
VL 44
IS 10
BP 759
EP 765
DI 10.1055/s-0032-1321866
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 007CI
UT WOS:000308866000007
PM 22951902
ER
PT J
AU Ahmad, F
Degerman, E
Manganiello, VC
AF Ahmad, F.
Degerman, E.
Manganiello, V. C.
TI Cyclic Nucleotide Phosphodiesterase 3 Signaling Complexes
SO HORMONE AND METABOLIC RESEARCH
LA English
DT Review
DE phosphodiesterase; protein kinase A; signalosomes
ID INHIBITED CAMP-PHOSPHODIESTERASE; INSULIN-INDUCED PHOSPHORYLATION;
SITE-DIRECTED MUTAGENESIS; ACTIVATED PROTEIN-KINASE; ADULT CARDIAC
MYOCYTES; RAT ADIPOCYTES; PHOSPHATIDYLINOSITOL 3-KINASE;
SARCOPLASMIC-RETICULUM; MOLECULAR-CLONING; HUMAN PLATELETS
AB The superfamily of cyclic nucleotide phosphodiesterases is comprised of 11 gene families. By hydrolyzing cAMP and cGMP, PDEs are major determinants in the regulation of intracellular concentrations of cyclic nucleotides and cyclic nucleotide-dependent signaling pathways. Two PDE3 subfamilies, PDE3A and PDE3B, have been described. PDE3A and PDE3B hydrolyze cAMP and cGMP with high affinity in a mutually competitive manner and are regulators of a number of important cAMP- and cGMP-mediated processes. PDE3B is relatively more highly expressed in cells of importance for the regulation of energy homeostasis, including adipocytes, hepatocytes, and pancreatic beta-cells, whereas PDE3A is more highly expressed in heart, platelets, vascular smooth muscle cells, and oocytes. Major advances have been made in understanding the different physiological impacts and biochemical basis for recruitment and subcellular localizations of different PDEs and PDE-containing macromolecular signaling complexes or signalosomes. In these discrete compartments, PDEs control cyclic nucleotide levels and regulate specific physiological processes as components of individual signalosomes which are tethered at specific locations and which contain PDEs together with cyclic nucleotide-dependent protein kinases (PKA and PKG), adenylyl cyclases, Epacs (guanine nucleotide exchange proteins activated by cAMP), phosphoprotein phosphatases, A-Kinase anchoring proteins (AKAPs), and pathway-specific regulators and effectors. This article highlights the identification of different PDE3A- and PDE3B-containing signalosomes in specialized subcellular compartments, which can increase the specificity and efficiency of intracellular signaling and be involved in the regulation of different cAMP-mediated metabolic processes.
C1 [Ahmad, F.] NHLBI, Cardiovasc Pulm Branch, NIH, Bethesda, MD 20892 USA.
[Degerman, E.] Lund Univ, Div Diabet Metab & Endocrinol, Dept Expt Med Sci, Lund, Sweden.
RP Ahmad, F (reprint author), NHLBI, Cardiovasc Pulm Branch, NIH, Bethesda, MD 20892 USA.
EM ahmadF@NHLBI.NIH.GOV
FU Intramural NIH HHS
NR 101
TC 17
Z9 17
U1 3
U2 13
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0018-5043
J9 HORM METAB RES
JI Horm. Metab. Res.
PD SEP
PY 2012
VL 44
IS 10
BP 776
EP 785
DI 10.1055/s-0032-1312646
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 007CI
UT WOS:000308866000009
PM 22692928
ER
PT J
AU Njajou, OT
Cawthon, RM
Blackburn, EH
Harris, TB
Li, R
Sanders, JL
Newman, AB
Nalls, M
Cummings, SR
Hsueh, WC
AF Njajou, O. T.
Cawthon, R. M.
Blackburn, E. H.
Harris, T. B.
Li, R.
Sanders, J. L.
Newman, A. B.
Nalls, M.
Cummings, S. R.
Hsueh, W-C
CA Hlth ABC Study
TI Shorter telomeres are associated with obesity and weight gain in the
elderly
SO INTERNATIONAL JOURNAL OF OBESITY
LA English
DT Article
DE telomere length; adiposity; telomeres; aging
ID OXIDATIVE STRESS; INSULIN-RESISTANCE; LENGTH; ADIPOSITY; DISEASE;
INFLAMMATION; SENESCENCE; MORTALITY; CELLS; OLDER
AB OBJECTIVE: Obesity and shorter telomeres are commonly associated with elevated risk for age-related diseases and mortality. Whether telomere length (TL) may be associated with obesity or variations in adiposity is not well established. Therefore, we set out to test the hypothesis that TL may be a risk factor for increased adiposity using data from a large population-based cohort study.
DESIGN: Levels of adiposity were assessed in six ways (obesity status, body mass index (BMI), the percentage of body fat or % body fat, leptin, visceral and subcutaneous fat mass) in 2721 elderly subjects (42% black and 58% white). Associations between TL measured in leukocytes at baseline and adiposity traits measured at baseline, and three of these traits after 7 years of follow-up were tested using regression models adjusting for important covariates. Additionally, we look at weight changes and relative changes in BMI and % body fat between baseline and follow-up.
RESULTS: At baseline, TL was negatively associated with % body fat (beta = -0.35 +/- 0.09, P = 0.001) and subcutaneous fat (beta = -2.66 +/- 1.07, P = 0.01), and positively associated with leptin after adjusting for % body fat (beta = -0.32 +/- 0.14, P = 0.001), but not with obesity, BMI or visceral fat. Prospective analyses showed that longer TL was associated with positive percent change between baseline and 7-year follow-up for both BMI (beta = 0.48 +/- 0.20, P = 0.01) and % body fat (beta = 0.42 +/- 0.23, P = 0.05).
CONCLUSION: Our study suggests that shorter TL may be a risk factor for increased adiposity. Coupling with previous reports on their reversed roles, the relationship between adiposity and TL may be complicated and may warrant more prospective studies.
C1 [Hsueh, W-C] Univ Calif San Francisco, Dept Med, Sch Med, San Francisco, CA 94143 USA.
[Cawthon, R. M.] Univ Utah, Dept Human Genet, Salt Lake City, UT USA.
[Blackburn, E. H.] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.
[Harris, T. B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Li, R.] Univ Tennessee, Dept Prevent Med, Memphis, TN USA.
[Sanders, J. L.; Newman, A. B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Nalls, M.] NIA, Mol Genet Sect, Neurogenet Lab, Bethesda, MD 20892 USA.
[Cummings, S. R.] Calif Pacific Med Ctr, Geraldine Brush Canc Res Inst, San Francisco Coordinating Ctr, San Francisco, CA 94115 USA.
RP Hsueh, WC (reprint author), Univ Calif San Francisco, Dept Med, Sch Med, 513 Parnassus Ave,HSE 672C, San Francisco, CA 94143 USA.
EM wen-chi.hsueh@ucsf.edu
RI Newman, Anne/C-6408-2013
OI Newman, Anne/0000-0002-0106-1150
FU Intramural Research Program of the National Institute on Aging, NIH
contracts [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, K01 AG022782,
R01 AG023692]; Training in Molecular and Genetic Epidemiology of Cancer,
National Institutes of Health, National Cancer Institute grant [R25
CA112355]
FX This study was supported in part by the Intramural Research Program of
the National Institute on Aging, NIH contracts (N01-AG-6-2101,
N01-AG-6-2103 and N01-AG-6-2106) and grants (K01 AG022782 and R01
AG023692). Dr OT Njajou is supported by the Training in Molecular and
Genetic Epidemiology of Cancer, National Institutes of Health, National
Cancer Institute grant (R25 CA112355).
NR 30
TC 29
Z9 30
U1 1
U2 16
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 2012
VL 36
IS 9
BP 1176
EP 1179
DI 10.1038/ijo.2011.196
PG 4
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 003SK
UT WOS:000308631400007
PM 22005719
ER
PT J
AU Albert, M
Aydin, S
Su, H
Chatila, T
Alsum, Z
Heinz, V
Al-Herz, W
Keles, S
Picard, C
Gathmann, B
Honig, M
Gennery, A
Al-Mousa, H
Geha, RS
Sawalle-Belohradsky, J
Notheis, G
Schwarze, CP
Metin, A
Gaspar, B
Bienemann, K
Schulz, A
Thiel, J
Duckers, G
Kuijpers, TW
van Montfrans, JM
Ifversen, M
Barlogis, V
Hawwari, A
Holland, SM
Rezaei, N
Al Zahrani, D
Kilic, SS
Genel, F
Kostyuchenko, L
Kainulainen, L
Porras, O
Kumar, A
Ehl, S
Aytekin, C
Gonzalez-Granado, LI
Abbott, J
Kutukculer, N
Marodi, L
Grimbacher, B
Renner, ED
Ochs, H
Belohradsky, BH
Sanal, O
Freeman, AF
Engelhardt, KR
AF Albert, M.
Aydin, S.
Su, H.
Chatila, T.
Alsum, Z.
Heinz, V.
Al-Herz, W.
Keles, S.
Picard, C.
Gathmann, B.
Hoenig, M.
Gennery, A.
Al-Mousa, H.
Geha, R. S.
Sawalle-Belohradsky, J.
Notheis, G.
Schwarze, C. P.
Metin, A.
Gaspar, B.
Bienemann, K.
Schulz, A.
Thiel, J.
Dueckers, G.
Kuijpers, T. W.
van Montfrans, J. M.
Ifversen, M.
Barlogis, V.
Hawwari, A.
Holland, S. M.
Rezaei, N.
Al Zahrani, D.
Kilic, S. S.
Genel, F.
Kostyuchenko, L.
Kainulainen, L.
Porras, O.
Kumar, A.
Ehl, S.
Aytekin, C.
Gonzalez-Granado, L. I.
Abbott, J.
Kutukculer, N.
Marodi, L.
Grimbacher, B.
Renner, E. D.
Ochs, H.
Belohradsky, B. H.
Sanal, O.
Freeman, A. F.
Engelhardt, K. R.
CA DOCK8 Study Grp
TI CLINICAL PRESENTATION AND LONG-TERM OUTCOME OF DOCK8 DEFICIENCY - A
SURVEY OF 134 PATIENTS
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 15th Biennial Meeting of the
European-Society-for-Primary-Immunodeficiency (ESID)
CY OCT 03-06, 2012
CL Florence, ITALY
SP European Soc Primary Immunodeficiency (ESID), Int Nursing Grp Immunodeficiencies (INGID), Int Patient Org Primary Immunodeficiencies (IPOPI)
C1 [Aydin, S.; Heinz, V.; Sawalle-Belohradsky, J.; Notheis, G.; Renner, E. D.; Belohradsky, B. H.] Dr von Haunersches Kinderspital, Munich, Germany.
[Su, H.; Holland, S. M.; Freeman, A. F.] NIH, Bethesda, MD 20892 USA.
[Chatila, T.; Geha, R. S.] Harvard Univ, Sch Med, Boston, MA USA.
[Alsum, Z.; Al-Mousa, H.; Hawwari, A.] King Faisal Specialist Hosp & Res Ctr, Ryadh, Saudi Arabia.
[Al-Herz, W.] Kuwait Univ, Kuwait, Kuwait.
[Keles, S.] Selcuk Univ, Konya, Turkey.
[Picard, C.] Hop Necker Enfants Malad, Paris, France.
[Gathmann, B.; Ehl, S.; Grimbacher, B.; Engelhardt, K. R.] Ctr Chron Immunodeficiency, Freiburg, Germany.
[Gathmann, B.] ESID Registry Working Party, Freiburg, Germany.
[Hoenig, M.; Schulz, A.] Univ Kinderklin Ulm, Ulm, Germany.
[Gennery, A.] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Schwarze, C. P.] Univ Childrens Hosp, Tubingen, Germany.
[Metin, A.] Ankara Childrens Hematol Oncol Training Hosp, Ankara, Turkey.
[Gaspar, B.] UCL Inst Child Hlth, London, England.
[Bienemann, K.] Univ Dusseldorf, Dusseldorf, Germany.
[Thiel, J.] Univ Hosp Freiburg, Freiburg, Germany.
[Dueckers, G.] HELIOS Klinikum Krefeld, Krefeld, Germany.
[Kuijpers, T. W.] Univ Amsterdam, Acad Med Ctr, Emma Childrens Hosp, NL-1105 AZ Amsterdam, Netherlands.
[van Montfrans, J. M.] Univ Med Ctr Utrecht, Wilhelmina Childrens Hosp, Utrecht, Netherlands.
[Ifversen, M.] Univ Copenhagen Hosp, DK-2100 Copenhagen, Denmark.
[Barlogis, V.] Hop Enfants La Timone, Marseille, France.
[Rezaei, N.] Univ Tehran Med Sci, Childrens Med Ctr, Tehran, Iran.
[Al Zahrani, D.] King Abdul Aziz Med City, Jeddah, Saudi Arabia.
[Kilic, S. S.] Uludag Univ, Fac Med, Bursa, Turkey.
[Genel, F.] Dr Behcet Uz Childrens Hosp, Izmir, Turkey.
[Kostyuchenko, L.] Western Ctr Chlidren Immunol, Kiev, Ukraine.
[Kainulainen, L.] Turku Univ Hosp, FIN-20520 Turku, Finland.
[Porras, O.] Hosp Nacl Ninos Carlos Saenz Herrera, San Jose, Costa Rica.
[Kumar, A.] Cincinnati Childrens Hosp, Cincinnati, OH USA.
[Aytekin, C.] Dr Sami Ulus Matern & Childrens Res & Educ Hosp, Ankara, Turkey.
[Gonzalez-Granado, L. I.] Hosp 12 Octubre, E-28041 Madrid, Spain.
[Abbott, J.] Univ Colorado, Denver, CO 80202 USA.
[Kutukculer, N.] Ege Univ, Izmir, Turkey.
[Marodi, L.] Univ Debrecen, H-4012 Debrecen, Hungary.
[Grimbacher, B.; Engelhardt, K. R.] Royal Free & Univ Coll London, Dept Immunol & Mol Pathol, London, England.
[Ochs, H.] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA.
[Sanal, O.] Hacettepe Univ, Ankara, Turkey.
RI Su, Helen/H-9541-2015; Rezaei, Nima/B-4245-2008; Abbott,
Jordan/P-2509-2016
OI Su, Helen/0000-0002-5582-9110; Rezaei, Nima/0000-0002-3836-1827; Abbott,
Jordan/0000-0001-6334-5266
NR 0
TC 1
Z9 1
U1 0
U2 3
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
EI 1573-2592
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD SEP
PY 2012
VL 32
SU 1
BP 3
EP 3
PG 1
WC Immunology
SC Immunology
GA 005CU
UT WOS:000308728900004
ER
PT J
AU Rosenzweig, S
Sadat, M
Moir, S
Lusso, P
Kaplan, G
Wolfe, L
Memoli, M
He, M
Hussein, N
Nievas, E
Mitchell, R
Garofalo, M
Ireland, D
Grunes, C
Cimbro, R
Chun, TW
Bristol, T
Adams, D
Marciano, B
Calvo, K
Stoddard, J
Justement, S
Jaques, J
Chiorini, J
Priel, DL
Kuhns, D
DiPasquale, G
Verthelyi, D
AF Rosenzweig, S.
Sadat, M.
Moir, S.
Lusso, P.
Kaplan, G.
Wolfe, L.
Memoli, M.
He, M.
Hussein, N.
Nievas, E.
Mitchell, R.
Garofalo, M.
Ireland, D.
Grunes, C.
Cimbro, R.
Chun, T-W.
Bristol, T.
Adams, D.
Marciano, B.
Calvo, K.
Stoddard, J.
Justement, S.
Jaques, J.
Chiorini, J.
Priel, D. Long
Kuhns, D.
DiPasquale, G.
Verthelyi, D.
TI GENETIC DEFECTS IN MOGS ASSOCIATE SEVERE HYPOGAMMAGLOBULINEMIA WITH
NATURAL RESISTANCE TO VIRAL INFECTIONS
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 15th Biennial Meeting European-Society-for-Immunodeficiency (ESID)
CY OCT 03-06, 2012
CL Florence, ITALY
SP European Soc Immunodeficiency (ESID), Int Nursing Grp Immunodeficiencies (INGID), Int Patient Org Primary Immunodeficiencies (IPOPI)
C1 [Rosenzweig, S.; Sadat, M.; Hussein, N.; Nievas, E.; Mitchell, R.] NIAID, Infect Dis Susceptibil Unit, LHD, NIH, Bethesda, MD 20892 USA.
[Kaplan, G.; Ireland, D.; Grunes, C.; Jaques, J.; Verthelyi, D.] US FDA, Bethesda, MD 20014 USA.
[Wolfe, L.; Adams, D.] NHGRI, NIH, Bethesda, MD 20892 USA.
[He, M.] Emory Univ, Atlanta, GA 30322 USA.
[Calvo, K.; Stoddard, J.] NIH, CC, Bethesda, MD 20892 USA.
[Chiorini, J.; DiPasquale, G.] NIDCR, NIH, Bethesda, MD USA.
[Priel, D. Long; Kuhns, D.] SAIC, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD SEP
PY 2012
VL 32
SU 1
BP 25
EP 25
PG 1
WC Immunology
SC Immunology
GA 005CU
UT WOS:000308728900043
ER
PT J
AU Haverkamp, MH
van de Vosse, E
Goldbach-Mansky, R
Holland, SM
AF Haverkamp, M. H.
van de Vosse, E.
Goldbach-Mansky, R.
Holland, S. M.
TI IMPAIRED CYTOKINE RESPONSES TO STIMULATION IN PATIENTS WITH
CRYOPYRIN-ASSOCIATED PERIODIC SYNDROME (CAPS)
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 15th Biennial Meeting European-Society-for-Immunodeficiency (ESID)
CY OCT 03-06, 2012
CL Florence, ITALY
SP European Soc Immunodeficiency (ESID), Int Nursing Grp Immunodeficiencies (INGID), Int Patient Org Primary Immunodeficiencies (IPOPI)
C1 [Haverkamp, M. H.; van de Vosse, E.] Leiden Univ, Med Ctr, Dept Infect Dis, Leiden, Netherlands.
[Haverkamp, M. H.; Holland, S. M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Goldbach-Mansky, R.] NIAID, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD SEP
PY 2012
VL 32
SU 1
BP 33
EP 33
PG 1
WC Immunology
SC Immunology
GA 005CU
UT WOS:000308728900058
ER
PT J
AU Walter, JE
Matthew, D
Lee, YN
Recher, M
Patrizi, L
Al-Herz, W
Cowan, M
Puck, J
Bleesing, J
Filipovich, L
Niehues, T
Schuetz, C
Drucker, G
Malech, H
De Ravin, SS
Uzel, G
Facchetti, F
Gennery, A
Alenezi, HM
Chinen, J
Dbaibo, G
El Ghazali, G
Pasic, S
Chen, K
Nadeau, K
Abraham, R
Giliani, S
Balboni, M
Browne, S
Notarangelo, LD
AF Walter, J. E.
Matthew, D.
Lee, Y. N.
Recher, M.
Patrizi, L.
Al-Herz, W.
Cowan, M.
Puck, J.
Bleesing, J.
Filipovich, L.
Niehues, T.
Schuetz, C.
Drucker, G.
Malech, H.
De Ravin, S. S.
Uzel, G.
Facchetti, F.
Gennery, A.
Alenezi, H. M.
Chinen, J.
Dbaibo, G.
El Ghazali, G.
Pasic, S.
Chen, K.
Nadeau, K.
Abraham, R.
Giliani, S.
Balboni, M.
Browne, S.
Notarangelo, L. D.
TI CHARACTERIZATION OF AUTOANTIBODY PROFILE AMONG PATIENTS WITH PRIMARY
IMMUNODEFICIENCY SECONDARY TO RAG MUTATIONS
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 15th Biennial Meeting European-Society-for-Immunodeficiency (ESID)
CY OCT 03-06, 2012
CL Florence, ITALY
SP European Soc Immunodeficiency (ESID), Int Nursing Grp Immunodeficiencies (INGID), Int Patient Org Primary Immunodeficiencies (IPOPI)
C1 [Walter, J. E.] Harvard Univ, Sch Med, Dept Pediat, Massachusetts Gen Hosp Children,Div Allergy Immun, Boston, MA 02115 USA.
[Walter, J. E.; Matthew, D.; Lee, Y. N.; Patrizi, L.; Notarangelo, L. D.] Childrens Hosp Boston, Dept Pediat, Div Immunol, Boston, MA USA.
[Recher, M.] Univ Basel Hosp, Dept Internal Med, CH-4031 Basel, Switzerland.
[Al-Herz, W.; Alenezi, H. M.] Al Sabah Hosp, Dept Pediat, Allergy & Clin Immunol Unit, Kuwait, Kuwait.
[Cowan, M.; Puck, J.] Univ Calif San Francisco, San Francisco UCSF Sch Med, Dept Pediat, San Francisco, CA USA.
[Cowan, M.; Puck, J.] UCSF Childrens Hosp, San Francisco, CA USA.
[Bleesing, J.; Filipovich, L.] Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH USA.
[Niehues, T.; Drucker, G.] Univ Dusseldorf, Helios Klinikum Krefeld Acad Hosp, Ctr Child Hlth & Adolescence, Dusseldorf, Germany.
[Schuetz, C.] Univ Hosp Ulm, Dept Pediat & Adolescent Med, Ulm, Germany.
[Malech, H.; De Ravin, S. S.] NIAID, Host Def Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Uzel, G.; Browne, S.] NIAID, Infect Dis Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Facchetti, F.] Univ Brescia, Dept Pathol, Brescia, Italy.
[Gennery, A.] Univ Newcastle, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England.
[Chinen, J.] Texas Childrens Hosp, Baylor Coll Med, Dept Pediat, Sect Allergy & Immunol, Houston, TX 77030 USA.
[Dbaibo, G.] Amer Univ Beirut, Dept Pediat & Adolescent Med, Beirut, Lebanon.
[El Ghazali, G.] King Fahad Med City, Fac Med, Dept Immunol, Riyadh, Saudi Arabia.
[Pasic, S.] Mother & Child Hlth Inst, Dept Pediat Immunol, Beograd, Serbia.
[Chen, K.] Univ Utah, Dept Pediat, Salt Lake City, UT USA.
[Nadeau, K.; Balboni, M.] Stanford Sch Med, Div Allergy Immunol, Palo Alto, CA USA.
[Abraham, R.] Mayo Clin, Lab Med & Pathol, Rochester, MN USA.
[Giliani, S.] Univ Brescia, Pediat Clin, Brescia, Italy.
RI Notarangelo, Luigi/F-9718-2016; Facchetti, Fabio/E-7190-2010
OI Notarangelo, Luigi/0000-0002-8335-0262; Facchetti,
Fabio/0000-0003-4975-2388
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD SEP
PY 2012
VL 32
SU 1
BP 44
EP 44
PG 1
WC Immunology
SC Immunology
GA 005CU
UT WOS:000308728900079
ER
PT J
AU Zago, CA
Jacob, CMA
Diniz, EMDA
Zerbini, C
Dorna, M
Fernandes, J
Rocha, V
Oliveira, JB
Carneiro-Sampaio, M
AF Zago, C. A.
Jacob, C. M. A.
Diniz, E. M. D. A.
Zerbini, C.
Dorna, M.
Fernandes, J.
Rocha, V.
Oliveira, J. B.
Carneiro-Sampaio, M.
TI T-CELL- AND ANTIBODY-MEDIATED AUTOIMMUNE MANIFESTATIONS IN SCID DUE TO
IL7RA MUTATIONS
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 15th Biennial Meeting European-Society-for-Immunodeficiency (ESID)
CY OCT 03-06, 2012
CL Florence, ITALY
SP European Soc Immunodeficiency (ESID), Int Nursing Grp Immunodeficiencies (INGID), Int Patient Org Primary Immunodeficiencies (IPOPI)
C1 [Zago, C. A.; Jacob, C. M. A.; Diniz, E. M. D. A.; Dorna, M.; Fernandes, J.; Rocha, V.; Carneiro-Sampaio, M.] Univ Sao Paulo, Fac Med, Dept Pediat, Sao Paulo, Brazil.
[Diniz, E. M. D. A.; Zerbini, C.] Univ Sao Paulo, HU, Sao Paulo, Brazil.
[Oliveira, J. B.] NIH, Serv Immunol, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RI Zerbini, Maria Claudia/D-1586-2012
OI Zerbini, Maria Claudia/0000-0002-7408-9816
NR 0
TC 0
Z9 0
U1 0
U2 2
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD SEP
PY 2012
VL 32
SU 1
BP 68
EP 69
PG 2
WC Immunology
SC Immunology
GA 005CU
UT WOS:000308728900131
ER
PT J
AU Aydin, S
Freeman, AF
Sanal, O
Al-Mousa, H
Matthes-Martin, S
Cuellar-Rodriguez, J
Hickstein, DD
Tavil, B
Azik, FM
Bittner, TC
Bredius, RG
Ayvaz, D
Kuskonmaz, B
Honig, M
Schulz, A
Picard, C
Barlogis, V
Gennery, A
Ifversen, M
van Montfrans, JM
Kuijpers, TW
Duckers, G
Al-Herz, W
Pai, SY
Geha, RS
Notheis, G
Schwarze, CP
Schuster, F
Gathmann, B
Grimbacher, B
Gaspar, B
Belohradsky, BH
Ochs, H
Renner, E
Chatila, T
Engelhardt, KR
Albert, MH
AF Aydin, S.
Freeman, A. F.
Sanal, O.
Al-Mousa, H.
Matthes-Martin, S.
Cuellar-Rodriguez, J.
Hickstein, D. D.
Tavil, B.
Azik, F. M.
Bittner, T. C.
Bredius, R. G.
Ayvaz, D.
Kuskonmaz, B.
Hoenig, M.
Schulz, A.
Picard, C.
Barlogis, V.
Gennery, A.
Ifversen, M.
van Montfrans, J. M.
Kuijpers, T. W.
Dueckers, G.
Al-Herz, W.
Pai, S. Y.
Geha, R. S.
Notheis, G.
Schwarze, C. P.
Schuster, F.
Gathmann, B.
Grimbacher, B.
Gaspar, B.
Belohradsky, B. H.
Ochs, H.
Renner, E.
Chatila, T.
Engelhardt, K. R.
Albert, M. H.
TI MANAGEMENT OF DOCK8 DEFICIENCY BY HEMATOPOIETIC STEM CELL
TRANSPLANTATION (HSCT)
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 15th Biennial Meeting European-Society-for-Immunodeficiency (ESID)
CY OCT 03-06, 2012
CL Florence, ITALY
SP European Soc Immunodeficiency (ESID), Int Nursing Grp Immunodeficiencies (INGID), Int Patient Org Primary Immunodeficiencies (IPOPI)
C1 [Aydin, S.; Bittner, T. C.; Notheis, G.; Belohradsky, B. H.; Renner, E.; Albert, M. H.] Dr von Haunersches Kinderspital, Munich, Germany.
[Freeman, A. F.; Cuellar-Rodriguez, J.; Hickstein, D. D.] NIH, Bethesda, MD 20892 USA.
[Sanal, O.; Ayvaz, D.; Kuskonmaz, B.] Hacettepe Univ, Ankara, Turkey.
[Al-Mousa, H.] King Faisal Specialist Hosp & Res Ctr, Ryadh, Saudi Arabia.
[Matthes-Martin, S.] Med Univ Vienna, St Anna Childrens Hosp, Dept Pediat, Vienna, Austria.
[Tavil, B.; Azik, F. M.] Ankara Childrens Hematol Oncol Training Hosp, Ankara, Turkey.
[Bredius, R. G.] Leiden Univ, Med Ctr, Leiden, Netherlands.
[Hoenig, M.; Schulz, A.] Univ Kinderklin Ulm, Ulm, Germany.
[Picard, C.] Hop Necker Enfants Malad, Paris, France.
[Barlogis, V.] Hop Enfants La Timone, Marseille, France.
[Gennery, A.] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Ifversen, M.] Copenhagen Univ Hosp, Copenhagen, Denmark.
[van Montfrans, J. M.] Wilhelmina Childrens Hosp, Univ Med Ctr Utrecht, Utrecht, Netherlands.
[Kuijpers, T. W.] Emma Childrens Hosp, Acad Med Ctr, Amsterdam, Netherlands.
[Dueckers, G.] HELIOS Klinikum Krefeld, Krefeld, Germany.
[Al-Herz, W.] Kuwait Univ, Kuwait, Kuwait.
[Pai, S. Y.; Geha, R. S.; Chatila, T.] Harvard Univ, Sch Med, Boston, MA USA.
[Schwarze, C. P.] Univ Childrens Hosp, Tubingen, Germany.
[Schuster, F.] Univ Hosp Duesseldorf, Dusseldorf, Germany.
[Gathmann, B.; Engelhardt, K. R.] Ctr Chron Immunodeficiency, Freiburg, Germany.
[Gathmann, B.] ESID Registry Working Party, Freiburg, Germany.
[Grimbacher, B.; Engelhardt, K. R.] Royal Free, Dept Immunol & Mol Pathol, London, England.
[Grimbacher, B.; Engelhardt, K. R.] UCL, London, England.
[Gaspar, B.] UCL Inst Child Hlth, London, England.
[Ochs, H.] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA.
RI Cagdas Ayvaz, Deniz Nazire/H-3212-2015; Azik, Fatih/C-1234-2014
OI Azik, Fatih/0000-0001-5715-4244
NR 0
TC 0
Z9 0
U1 0
U2 4
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD SEP
PY 2012
VL 32
SU 1
BP 127
EP 128
PG 2
WC Immunology
SC Immunology
GA 005CU
UT WOS:000308728900250
ER
PT J
AU Candotti, F
Shaw, KL
Sokolic, R
Carbonaro, D
Muul, L
Mishra, S
Garabedian, E
Fu, PY
Jagadeesh, GJ
Silvin, C
Hershfield, MS
Blaese, RM
Kohn, DB
AF Candotti, F.
Shaw, K. L.
Sokolic, R.
Carbonaro, D.
Muul, L.
Mishra, S.
Garabedian, E.
Fu, P. -Y.
Jagadeesh, G. J.
Silvin, C.
Hershfield, M. S.
Blaese, R. M.
Kohn, D. B.
TI US RESULTS OF GENE THERAPY FOR ADENOSINE DEAMINASE DEFICIENCY
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 15th Biennial Meeting European-Society-for-Immunodeficiency (ESID)
CY OCT 03-06, 2012
CL Florence, ITALY
SP European Soc Immunodeficiency (ESID), Int Nursing Grp Immunodeficiencies (INGID), Int Patient Org Primary Immunodeficiencies (IPOPI)
C1 [Candotti, F.; Sokolic, R.; Muul, L.; Garabedian, E.; Jagadeesh, G. J.; Silvin, C.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
[Shaw, K. L.; Carbonaro, D.; Mishra, S.; Fu, P. -Y.; Kohn, D. B.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Hershfield, M. S.] Duke Univ, Med Ctr, Durham, NC USA.
[Blaese, R. M.] Immune Deficiency Fdn, Towson, MD USA.
RI Sokolic, Robert/I-6072-2012
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD SEP
PY 2012
VL 32
SU 1
BP 130
EP 130
PG 1
WC Immunology
SC Immunology
GA 005CU
UT WOS:000308728900255
ER
PT J
AU Ikawa, Y
Hess, R
Dorward, H
Gochuico, BR
Gahl, WA
Candotti, F
AF Ikawa, Y.
Hess, R.
Dorward, H.
Gochuico, B. R.
Gahl, W. A.
Candotti, F.
TI GENERATING A LENTIVIRAL GENE TRANSFER SYSTEM FOR HERMANSKY-PUDLAK
SYNDROME
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 15th Biennial Meeting European-Society-for-Immunodeficiency (ESID)
CY OCT 03-06, 2012
CL Florence, ITALY
SP European Soc Immunodeficiency (ESID), Int Nursing Grp Immunodeficiencies (INGID), Int Patient Org Primary Immunodeficiencies (IPOPI)
C1 [Ikawa, Y.; Hess, R.; Dorward, H.; Gochuico, B. R.; Gahl, W. A.; Candotti, F.] NHGRI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD SEP
PY 2012
VL 32
SU 1
BP 141
EP 142
PG 2
WC Immunology
SC Immunology
GA 005CU
UT WOS:000308728900278
ER
PT J
AU Rissone, A
Jagadeesh, GJ
Simon, K
Bishop, K
English, M
Blake, T
Sood, R
Candotti, F
AF Rissone, A.
Jagadeesh, G. J.
Simon, K.
Bishop, K.
English, M.
Blake, T.
Sood, R.
Candotti, F.
TI MODELING RETICULAR DYSGENESIS IN ZEBRAFISH
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 15th Biennial Meeting European-Society-for-Immunodeficiency (ESID)
CY OCT 03-06, 2012
CL Florence, ITALY
SP European Soc Immunodeficiency (ESID), Int Nursing Grp Immunodeficiencies (INGID), Int Patient Org Primary Immunodeficiencies (IPOPI)
C1 [Candotti, F.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD SEP
PY 2012
VL 32
SU 1
BP 230
EP 230
PG 1
WC Immunology
SC Immunology
GA 005CU
UT WOS:000308728900467
ER
PT J
AU Lopez-Herrera, G
Tampella, G
Pan-Hammarstrom, Q
Herholz, P
Trujillo-Vargas, CM
Phadwal, K
Simon, AK
Moutschen, M
Etzioni, A
Mory, A
Srugo, I
Melamed, D
Hultenby, K
Liu, C
Baronio, M
Vitali, M
Philippet, P
Dideberg, V
Aghamohammadi, A
Rezai, N
Enright, V
Du, L
Salzer, U
Eibel, H
Pfeifer, D
Veelken, H
Stauss, H
Lougaris, V
Plebani, A
Gertz, EM
Schaffer, AA
Hammarstrom, L
Grimbacher, B
AF Lopez-Herrera, G.
Tampella, G.
Pan-Hammarstrom, Q.
Herholz, P.
Trujillo-Vargas, C. M.
Phadwal, K.
Simon, A. K.
Moutschen, M.
Etzioni, A.
Mory, A.
Srugo, I.
Melamed, D.
Hultenby, K.
Liu, C.
Baronio, M.
Vitali, M.
Philippet, P.
Dideberg, V.
Aghamohammadi, A.
Rezai, N.
Enright, V.
Du, L.
Salzer, U.
Eibel, H.
Pfeifer, D.
Veelken, H.
Stauss, H.
Lougaris, V.
Plebani, A.
Gertz, E. M.
Schaeffer, A. A.
Hammarstrom, L.
Grimbacher, B.
TI DELETERIOUS LRBA MUTATIONS IN A NOVEL SYNDROME OF IMMUNE DEFICIENCY AND
AUTOIMMUNITY
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 15th Biennial Meeting European-Society-for-Immunodeficiency (ESID)
CY OCT 03-06, 2012
CL Florence, ITALY
SP European Soc Immunodeficiency (ESID), Int Nursing Grp Immunodeficiencies (INGID), Int Patient Org Primary Immunodeficiencies (IPOPI)
C1 [Lopez-Herrera, G.; Trujillo-Vargas, C. M.; Enright, V.; Stauss, H.; Grimbacher, B.] UCL, Dept Immunol, Royal Free Hosp, Div Infect & Immun, London, England.
[Lopez-Herrera, G.] Natl Inst Pediat, Immunodeficiency Res Unit, Mexico City, DF, Mexico.
[Tampella, G.; Baronio, M.; Vitali, M.; Lougaris, V.; Plebani, A.] Univ Brescia, Pediat Clin, Spedali Civili Brescia, Brescia, Italy.
[Tampella, G.; Baronio, M.; Vitali, M.; Lougaris, V.; Plebani, A.] Univ Brescia, Inst Mol Med A Novicelli, Spedali Civili Brescia, Brescia, Italy.
[Pan-Hammarstrom, Q.; Hultenby, K.; Liu, C.; Du, L.; Hammarstrom, L.] Karolinska Univ, Karolinska Inst, Huddinge Hosp, Dept Lab Med, Stockholm, Sweden.
[Herholz, P.; Salzer, U.; Eibel, H.; Grimbacher, B.] Univ Med Ctr Freiburg, Ctr Chron Immunodeficiency, Freiburg, Germany.
[Trujillo-Vargas, C. M.] Univ Antioquia, Grp Primary Immunodeficiencies, Medellin, Colombia.
[Phadwal, K.; Simon, A. K.] Univ Oxford, John Radcliffe Hosp, Biomed Res Ctr,Translat Immunol Lab, Natl Inst Hlth Res,Nuffield Dept Med, Oxford OX3 9DU, England.
[Simon, A. K.] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Med Res Council,Human Immunol Unit, Oxford OX3 9DU, England.
[Moutschen, M.] Univ Liege, Inst Pathol, Ctr Immunol, Lab Immunoendocrinol, Liege, Belgium.
[Etzioni, A.; Mory, A.; Srugo, I.; Melamed, D.] Technion Israel Inst Technol, Div Pediat & Immunol, Rappaport Sch Med, Haifa, Israel.
[Liu, C.] N Sichuan Med Coll, Affiliated Hosp, Dept Pediat, Chengdu, Sichuan, Peoples R China.
[Philippet, P.] Ctr Hosp Chretien Esperance, Dept Pediat, Montegnee, Belgium.
[Dideberg, V.] Univ Liege, Ctr Human Genet, Liege, Belgium.
[Aghamohammadi, A.] Univ Tehran Med Sci, Children Med Ctr, Pediat Ctr Excellence, Res Ctr Immunodeficiencies, Tehran, Iran.
[Rezai, N.] Univ Tehran Med Sci, Mol Immunol Res Ctr, Sch Med, Tehran, Iran.
[Rezai, N.] Univ Tehran Med Sci, Dept Immunol, Sch Med, Tehran, Iran.
[Pfeifer, D.] Univ Freiburg, Med Ctr, Dept Hematol & Oncol, Freiburg, Germany.
[Veelken, H.] Leiden Univ, Med Ctr, Dept Hematol, Leiden, Netherlands.
[Gertz, E. M.; Schaeffer, A. A.] NIH, Natl Ctr Biotechnol Informat, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD SEP
PY 2012
VL 32
SU 1
BP 251
EP 251
PG 1
WC Immunology
SC Immunology
GA 005CU
UT WOS:000308728900513
ER
PT J
AU Engelhardt, KR
Gertz, EM
Keles, S
Schaffer, AA
Ceja, R
Sassi, A
Massaad, MJ
Mellouli, F
Benmustapha, I
Khemiri, M
Kilic, SS
Etzioni, A
Freeman, AF
Thiel, J
Schulze, I
Al-Herz, W
Metin, A
Sanal, O
Yeganeh, M
Niehues, T
Siepermann, K
Unal, E
Patiroglu, T
Dasouki, M
Yilmaz, M
Genel, F
Aytekin, C
Kutukculer, N
Somer, A
Kilic, M
Reisli, I
Camcioglu, Y
Gennery, AR
Cant, AJ
Jones, A
Gaspar, HB
Arkwright, PD
Pietrogrande, MC
Baz, Z
Al-Tamemi, S
Lougaris, V
Lefranc, G
Megarbane, A
Boutros, J
Galal, N
Bejaoui, M
Barbouche, R
Geha, RS
Chatila, TA
Grimbacher, B
AF Engelhardt, K. R.
Gertz, E. M.
Keles, S.
Schaeffer, A. A.
Ceja, R.
Sassi, A.
Massaad, M. J.
Mellouli, F.
Benmustapha, I.
Khemiri, M.
Kilic, S. S.
Etzioni, A.
Freeman, A. F.
Thiel, J.
Schulze, I.
Al-Herz, W.
Metin, A.
Sanal, O.
Yeganeh, M.
Niehues, T.
Siepermann, K.
Unal, E.
Patiroglu, T.
Dasouki, M.
Yilmaz, M.
Genel, F.
Aytekin, C.
Kutukculer, N.
Somer, A.
Kilic, M.
Reisli, I.
Camcioglu, Y.
Gennery, A. R.
Cant, A. J.
Jones, A.
Gaspar, H. B.
Arkwright, P. D.
Pietrogrande, M. C.
Baz, Z.
Al-Tamemi, S.
Lougaris, V.
Lefranc, G.
Megarbane, A.
Boutros, J.
Galal, N.
Bejaoui, M.
Barbouche, R.
Geha, R. S.
Chatila, T. A.
Grimbacher, B.
TI DOCK8 DEFICIENCY AND A DIAGNOSTIC SCORE TO DIFFERENTIATE IT FROM OTHER
HYPER-IGE SYNDROMES
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 15th Biennial Meeting European-Society-for-Immunodeficiency (ESID)
CY OCT 03-06, 2012
CL Florence, ITALY
SP European Soc Immunodeficiency (ESID), Int Nursing Grp Immunodeficiencies (INGID), Int Patient Org Primary Immunodeficiencies (IPOPI)
C1 [Engelhardt, K. R.; Thiel, J.; Schulze, I.; Grimbacher, B.] Univ Freiburg Klinikum, CCI, Freiburg, Germany.
[Engelhardt, K. R.; Grimbacher, B.] Royal Free Hosp, Dept Immunol & Mol Pathol, London NW3 2QG, England.
[Engelhardt, K. R.; Grimbacher, B.] UCL, London, England.
[Gertz, E. M.; Schaeffer, A. A.] NIH, US Dept HHS, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA.
[Keles, S.; Ceja, R.; Chatila, T. A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Div Immunol Allergy & Rheumatol, Los Angeles, CA 90095 USA.
[Keles, S.; Reisli, I.] Konya Univ, Div Pediat Allergy & Immunol, Konya, Turkey.
[Ceja, R.; Massaad, M. J.; Geha, R. S.; Chatila, T. A.] Childrens Hosp, Div Immunol, Boston, MA 02115 USA.
[Sassi, A.; Benmustapha, I.; Barbouche, R.] Inst Pasteur, Dept Immunol, Tunis, Tunisia.
[Mellouli, F.; Bejaoui, M.] Bone Marrow Transplantat Ctr, Dept Pediat, Tunis, Tunisia.
[Khemiri, M.] Childrens Hosp, Dept Pediat, Tunis, Tunisia.
[Kilic, S. S.] Uludag Univ, Fac Med, Dept Pediat Immunol, Bursa, Turkey.
[Etzioni, A.] Technion Israel Inst Technol, Meyers Children Hosp, Rambam Hlth Care Campus, Haifa, Israel.
[Etzioni, A.] Technion Israel Inst Technol, Rappaport Fac Med, Haifa, Israel.
[Freeman, A. F.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Al-Herz, W.] Kuwait Univ, Fac Med, Dept Pediat, Kuwait, Kuwait.
[Al-Herz, W.] Al Sabah Hosp, Allergy & Clin Immunol Unit, Kuwait, Kuwait.
[Metin, A.] Hacettepe Univ, Childrens Hosp, SB Ankara Diskapi Childrens Hosp, Pediat Immunol Unit, Ankara, Turkey.
[Sanal, O.] Hacettepe Univ, Childrens Hosp, Div Immunol, Ankara, Turkey.
[Yeganeh, M.] Univ Tehran Med Sci, Childrens Med Ctr, Immunol Asthma & Allergy Res Inst, Tehran, Iran.
[Niehues, T.; Siepermann, K.] HELIOS Klinikum Krefeld, Zentrum Kinder & Jugendmed, Krefeld, Germany.
[Unal, E.; Patiroglu, T.] Erciyes Univ, Fac Med, Div Pediat Immunol, Dept Pediat, Kayseri, Turkey.
[Dasouki, M.] Univ Kansas, Med Ctr, Dept Pediat, Kansas City, MO USA.
[Yilmaz, M.] Cukurova Univ, Adana, Turkey.
[Genel, F.] Behcet Uz State Hosp, Div Pediat Immunol, Izmir, Turkey.
[Aytekin, C.] Dr Sami Ulus State Hosp, Ankara, Turkey.
[Kutukculer, N.] Ege Univ, Fac Med, Dept Pediat, Izmir, Turkey.
[Somer, A.] Istanbul Univ, Fac Med, Div Infect Dis & Immunol, Istanbul, Turkey.
[Kilic, M.] Firat Univ, TR-23169 Elazig, Turkey.
[Camcioglu, Y.] Istanbul Univ, Cerrahpasa Med Fac, Div Pediat Allergy Immunol & Infect Dis, Istanbul, Turkey.
[Gennery, A. R.; Cant, A. J.] Newcastle Univ, Childrens Bone Marrow Transplant Unit, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Jones, A.; Gaspar, H. B.] Great Ormond St Hosp Sick Children, Dept Immunol, London, England.
[Arkwright, P. D.] Univ Manchester, Royal Manchester Childrens Hosp, Manchester, Lancs, England.
[Pietrogrande, M. C.] Univ Milan, Fdn Policlin IRCCS, Dept Pediat, Milan, Italy.
[Baz, Z.] St George Hosp Univ Med Ctr, Dept Pediat, Beirut, Lebanon.
[Al-Tamemi, S.] Sultan Qaboos Univ, Dept Pediat, Muscat, Oman.
[Lougaris, V.] Univ Brescia, Dept Pediat, Brescia, Italy.
[Lougaris, V.] Univ Brescia, Inst Mol Med A Novicelli, Brescia, Italy.
[Lefranc, G.] Univ Montpellier 2, Montpellier, France.
[Lefranc, G.] CNRS Inst Human Genet, Montpellier, France.
[Megarbane, A.] St Joseph Univ, Med Genet Unit, Beirut, Lebanon.
[Boutros, J.; Galal, N.] Cairo Univ, Specialized Pediat Hosp, Primary Immunodeficiency Clin, Cairo, Egypt.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD SEP
PY 2012
VL 32
SU 1
BP 332
EP 333
PG 2
WC Immunology
SC Immunology
GA 005CU
UT WOS:000308728900677
ER
PT J
AU Oliveira, JB
Kuehn, HS
Niemela, JE
Zhang, M
Stoddard, J
Santos, AR
Fleisher, T
Uzel, G
AF Oliveira, J. B.
Kuehn, H. S.
Niemela, J. E.
Zhang, M.
Stoddard, J.
Santos, A. R.
Fleisher, T.
Uzel, G.
TI LOSS-OF-FUNCTION MUTATION IN THE PROTEIN KINASE C DELTA (PKC delta)
GENE, PRKCD, CAUSES AN AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME-LIKE
DISEASE
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 15th Biennial Meeting European-Society-for-Immunodeficiency (ESID)
CY OCT 03-06, 2012
CL Florence, ITALY
SP European Soc Immunodeficiency (ESID), Int Nursing Grp Immunodeficiencies (INGID), Int Patient Org Primary Immunodeficiencies (IPOPI)
C1 [Oliveira, J. B.; Kuehn, H. S.; Niemela, J. E.; Zhang, M.; Stoddard, J.; Santos, A. R.; Fleisher, T.] NIH, Dep Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Oliveira, J. B.] Inst Med Integral Prof Fernando Figueira IMIP, Translat Med Lab, Recife, PE, Brazil.
[Uzel, G.] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD SEP
PY 2012
VL 32
SU 1
BP 381
EP 381
PG 1
WC Immunology
SC Immunology
GA 005CU
UT WOS:000308728900725
ER
PT J
AU Uzel, G
Kotlarz, D
Zietara, N
Lawrence, MG
Kardava, L
Hanson, E
Moir, S
Milner, JD
Mundlos, S
Klein, C
AF Uzel, G.
Kotlarz, D.
Zietara, N.
Lawrence, M. G.
Kardava, L.
Hanson, E.
Moir, S.
Milner, J. D.
Mundlos, S.
Klein, C.
TI LOSS OF FUNCTION MUTATIONS IN THE IL-21 RECEPTOR GENE CAUSES PRIMARY
IMMUNODEFICIENCY AND CONFERS SUSCEPTIBILITY TO CRYPTOSPORIDIUM AND
PNEUMOCYSTIS
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 15th Biennial Meeting European-Society-for-Immunodeficiency (ESID)
CY OCT 03-06, 2012
CL Florence, ITALY
SP European Soc Immunodeficiency (ESID), Int Nursing Grp Immunodeficiencies (INGID), Int Patient Org Primary Immunodeficiencies (IPOPI)
C1 [Uzel, G.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Kotlarz, D.; Zietara, N.; Klein, C.] Hannover Med Sch, Dept Pediat Hematology Oncol, D-3000 Hannover, Germany.
[Kotlarz, D.; Zietara, N.; Klein, C.] Univ Munich, Dept Pediat, Dr Von Hauner Childrens Hosp, Munich, Germany.
[Lawrence, M. G.; Milner, J. D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Kardava, L.] NIAID, Lab Immunoregulat, NIH, Bethesda, MD 20892 USA.
[Hanson, E.] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Mundlos, S.] Max Planck Inst Mol Genet, D-14195 Berlin, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD SEP
PY 2012
VL 32
SU 1
BP 385
EP 386
PG 2
WC Immunology
SC Immunology
GA 005CU
UT WOS:000308728900734
ER
PT J
AU Myles, IA
Hsu, AP
Pittaluga, S
Brown, M
Gurprasad, S
Lee, CCR
Datta, SK
Holland, SM
AF Myles, I. A.
Hsu, A. P.
Pittaluga, S.
Brown, M.
Gurprasad, S.
Lee, C-C. R.
Datta, S. K.
Holland, S. M.
CA Lab Clinical Infectious Dis
TI HYPOMORPHIC TAP2 DEFICIENCY
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 15th Biennial Meeting European-Society-for-Immunodeficiency (ESID)
CY OCT 03-06, 2012
CL Florence, ITALY
SP European Soc Immunodeficiency (ESID), Int Nursing Grp Immunodeficiencies (INGID), Int Patient Org Primary Immunodeficiencies (IPOPI)
C1 [Myles, I. A.; Hsu, A. P.; Brown, M.; Datta, S. K.; Holland, S. M.] NIAID, NIH, Bethesda, MD 20892 USA.
[Pittaluga, S.; Lee, C-C. R.] Dept Hlth & Human Serv, Lab Pathol, NIH, Bethesda, MD USA.
[Gurprasad, S.] Dept Hlth & Human Serv, Lab Med, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD SEP
PY 2012
VL 32
SU 1
BP 387
EP 387
PG 1
WC Immunology
SC Immunology
GA 005CU
UT WOS:000308728900736
ER
PT J
AU Barese, CN
Hunter, MJ
Tuschong, LM
Hickstein, D
Spencer, DM
Dunbar, CE
AF Barese, C. N.
Hunter, M. J.
Tuschong, L. M.
Hickstein, D.
Spencer, D. M.
Dunbar, C. E.
TI INDUCIBLE CASPASE 9 TRANSGENE AND THERAPEUTIC GENE CD18 FOR SAFER
CORRECTION OF HUMAN LEUKOCYTE ADHESION DEFICIENCY TYPE-1
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 15th Biennial Meeting European-Society-for-Immunodeficiency (ESID)
CY OCT 03-06, 2012
CL Florence, ITALY
SP European Soc Immunodeficiency (ESID), Int Nursing Grp Immunodeficiencies (INGID), Int Patient Org Primary Immunodeficiencies (IPOPI)
C1 [Barese, C. N.; Dunbar, C. E.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Hunter, M. J.; Tuschong, L. M.; Hickstein, D.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Spencer, D. M.] Bellicum Pharmaceut Inc, Houston, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD SEP
PY 2012
VL 32
SU 1
BP 399
EP 399
PG 1
WC Immunology
SC Immunology
GA 005CU
UT WOS:000308728900765
ER
PT J
AU Mace, EM
Uzel, G
Monaco-Shawver, L
Rosen, J
Dropulic, L
Cohen, JI
Sullivan, JL
Biron, CA
Spalding, C
Zerbe, CS
Hsu, AP
Holland, SM
Orange, JS
AF Mace, E. M.
Uzel, G.
Monaco-Shawver, L.
Rosen, J.
Dropulic, L.
Cohen, J. I.
Sullivan, J. L.
Biron, C. A.
Spalding, C.
Zerbe, C. S.
Hsu, A. P.
Holland, S. M.
Orange, J. S.
TI MUTATIONS IN GATA2 CAUSE HUMAN NK CELL DEFICIENCY WITH SPECIFIC LOSS OF
THE CD56(BRIGHT) SUBSET
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 15th Biennial Meeting European-Society-for-Immunodeficiency (ESID)
CY OCT 03-06, 2012
CL Florence, ITALY
SP European Soc Immunodeficiency (ESID), Int Nursing Grp Immunodeficiencies (INGID), Int Patient Org Primary Immunodeficiencies (IPOPI)
C1 [Mace, E. M.; Orange, J. S.] Baylor Coll Med, Houston, TX 77030 USA.
[Uzel, G.; Dropulic, L.; Cohen, J. I.; Spalding, C.; Zerbe, C. S.; Hsu, A. P.; Holland, S. M.] NIAID, NIH, Bethesda, MD 20892 USA.
[Monaco-Shawver, L.; Rosen, J.] Childrens Hosp Philadelphia, Res Inst, Philadelphia, PA 19104 USA.
[Sullivan, J. L.] Univ Massachusetts, Sch Med, Worcester, MA USA.
[Biron, C. A.] Brown Univ, Providence, RI 02912 USA.
[Orange, J. S.] Texas Childrens Hosp, Houston, TX 77030 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD SEP
PY 2012
VL 32
SU 1
BP 402
EP 402
PG 1
WC Immunology
SC Immunology
GA 005CU
UT WOS:000308728900771
ER
PT J
AU Mizesko, MC
Banerjee, PP
Mace, EM
Monaco-Shawver, L
Bernal, W
Sawalle-Belohradsky, J
Belohradsky, B
Freeman, AF
Holland, SM
Maul-Vavicic, A
Torgerson, TR
Ehl, S
Al-Herz, W
Chou, J
Geha, RS
Hanson, IC
Albert, MH
Renner, ED
Orange, JS
AF Mizesko, M. C.
Banerjee, P. P.
Mace, E. M.
Monaco-Shawver, L.
Bernal, W.
Sawalle-Belohradsky, J.
Belohradsky, B.
Freeman, A. F.
Holland, S. M.
Maul-Vavicic, A.
Torgerson, T. R.
Ehl, S.
Al-Herz, W.
Chou, J.
Geha, R. S.
Hanson, I. C.
Albert, M. H.
Renner, E. D.
Orange, J. S.
TI IMPAIRED NATURAL KILLER CELL FUNCTION IN DOCK8 DEFICIENCY
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 15th Biennial Meeting European-Society-for-Immunodeficiency (ESID)
CY OCT 03-06, 2012
CL Florence, ITALY
SP European Soc Immunodeficiency (ESID), Int Nursing Grp Immunodeficiencies (INGID), Int Patient Org Primary Immunodeficiencies (IPOPI)
C1 [Mizesko, M. C.; Banerjee, P. P.; Mace, E. M.; Hanson, I. C.; Orange, J. S.] Baylor Coll Med, Houston, TX 77030 USA.
[Mizesko, M. C.; Banerjee, P. P.; Hanson, I. C.; Orange, J. S.] Texas Childrens Hosp, Houston, TX 77030 USA.
[Monaco-Shawver, L.; Bernal, W.] Childrens Hosp Philadelphia, Res Inst, Philadelphia, PA 19104 USA.
[Sawalle-Belohradsky, J.; Belohradsky, B.; Albert, M. H.; Renner, E. D.] Univ Munich, Univ Childrens Hosp, Munich, Germany.
[Freeman, A. F.; Holland, S. M.] NIAID, NIH, Bethesda, MD 20892 USA.
[Maul-Vavicic, A.; Ehl, S.] Univ Med Ctr, Freiburg, Germany.
[Torgerson, T. R.] Univ Washington, Seattle, WA 98195 USA.
[Torgerson, T. R.] Seattle Childrens Hosp, Seattle, WA USA.
[Al-Herz, W.] Kuwait Univ, Kuwait, Kuwait.
[Al-Herz, W.] Allergy & Clin Immunol Unit, Kuwait, Kuwait.
[Chou, J.; Geha, R. S.] Boston Childrens Hosp, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD SEP
PY 2012
VL 32
SU 1
BP 402
EP 403
PG 2
WC Immunology
SC Immunology
GA 005CU
UT WOS:000308728900772
ER
PT J
AU Stephens, BE
Bann, CM
Watson, VE
Sheinkopf, SJ
Peralta-Carcelen, M
Bodnar, A
Yolton, K
Goldstein, RF
Dusick, AM
Wilson-Costello, DE
Acarregui, MJ
Pappas, A
Adams-Chapman, I
McGowan, EC
Heyne, RJ
Hintz, SR
Ehrenkranz, RA
Fuller, J
Das, A
Higgins, RD
Vohr, BR
AF Stephens, Bonnie E.
Bann, Carla M.
Watson, Victoria E.
Sheinkopf, Stephen J.
Peralta-Carcelen, Myriam
Bodnar, Anna
Yolton, Kimberly
Goldstein, Ricki F.
Dusick, Anna M.
Wilson-Costello, Deanne E.
Acarregui, Michael J.
Pappas, Athina
Adams-Chapman, Ira
McGowan, Elisabeth C.
Heyne, Roy J.
Hintz, Susan R.
Ehrenkranz, Richard A.
Fuller, Janell
Das, Abhik
Higgins, Rosemary D.
Vohr, Betty R.
CA Eunice Kennedy Shriver Natl Inst C
TI Screening for Autism Spectrum Disorders in Extremely Preterm Infants
SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS
LA English
DT Article
DE autism; prematurity; screening
ID BIRTH-WEIGHT; RISK-FACTORS; CHILDREN; OUTCOMES
AB Background: Extremely preterm(EP) infants screen positive for autism spectrum disorders (ASD) at high rates. However, it is not clear whether this is because of high rates of ASD in EPs or to high rates of false-positive screens for ASD in children with a high rate of underlying neurodevelopmental impairments. Combining a parent questionnaire designed to distinguish developmental delay from ASD with direct observation of infant behavior may more accurately screen for ASD in EPs. Objectives: To determine rates of positive screen for ASD at 18 to 22 months(m) in EPs using 3 screens; to determine factors associated with a positive screen. Methods: Five hundred fifty-four infants born <27 weeks were screened at 18 to 22 m using the Pervasive Developmental Disorders Screening test, second edition Stage 2, and the response to name and response to joint attention items from the Autism Diagnostic Observation Schedule. Infants with severe cerebral palsy, deafness, and blindness were excluded. Associations between positive screen and neonatal/ infant characteristics were determined. Results: Of 554 infants, 113 (20%) had >= 1 positive screen. 10% had a positive Pervasive Developmental Disorders Screening test, second edition, 6% response to name, 9% response to joint attention; in only 1 % all 3 screens were positive. Positive screen was associated with male gender, more hospital days, white race, lower maternal education, abnormal behavioral scores, and cognitive/ language delay. Conclusions: The use of 3 screens for ASD in EPs results in higher screen positive rates than use of 1 screen alone. Diagnostic confirmation is needed before true rates of ASD in EPs are known. (J Dev Behav Pediatr 33:535-541, 2012)
C1 [Stephens, Bonnie E.; Watson, Victoria E.; Vohr, Betty R.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02905 USA.
[Bann, Carla M.] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA.
[Sheinkopf, Stephen J.] Brown Univ, Women & Infants Hosp, Dept Psychiat & Human Behav, Ctr Study Children Risk,Brown Alpert Med Sch, Providence, RI USA.
[Peralta-Carcelen, Myriam] Univ Alabama Birmingham, Div Neonatol, Birmingham, AL USA.
[Bodnar, Anna] Univ Utah, Sch Med, Dept Pediat, Div Neonatol, Salt Lake City, UT USA.
[Yolton, Kimberly] Univ Cincinnati, Dept Pediat, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45221 USA.
[Goldstein, Ricki F.] Duke Univ, Dept Pediat, Durham, NC 27706 USA.
[Dusick, Anna M.] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN USA.
[Wilson-Costello, Deanne E.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA.
[Acarregui, Michael J.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA.
[Pappas, Athina] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
[Adams-Chapman, Ira] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA.
[Adams-Chapman, Ira] Childrens Healthcare Atlanta, Atlanta, GA USA.
[McGowan, Elisabeth C.] Floating Hosp Children, Tufts Med Ctr, Dept Pediat, Div Newborn Med, Boston, MA USA.
[Heyne, Roy J.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA.
[Hintz, Susan R.] Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA.
[Ehrenkranz, Richard A.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
[Fuller, Janell] Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA.
[Das, Abhik] RTI Int, Stat & Epidemiol Unit, Rockville, MD USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Stephens, BE (reprint author), Brown Univ, Women & Infants Hosp, Dept Pediat, 101 Dudley St, Providence, RI 02905 USA.
EM bstephens@wihri.org
FU NCATS NIH HHS [UL1 TR000041, UL1 TR000454]; NCRR NIH HHS [M01 RR000054,
M01 RR000039, M01 RR000064, M01 RR000070, M01 RR000997, M01 RR006022,
UL1 RR024139, UL1 RR024148, M01 RR000633, M01 RR000750, UL1 RR025764,
M01 RR008084, M01 RR000125, M01 RR000080, M01 RR000059, M01 RR000032,
M01 RR000030]; NICHD NIH HHS [U10 HD040689, U10 HD053119, U10 HD053089,
U10 HD036790, U10 HD034216, U10 HD027904, U10 HD027880, U10 HD027871,
U10 HD027856, U10 HD027853, U10 HD021385, U10 HD021364, U10 HD040492,
U10 HD053124, U10 HD053109, U10 HD027851]
NR 22
TC 25
Z9 25
U1 2
U2 29
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0196-206X
J9 J DEV BEHAV PEDIATR
JI J. Dev. Behav. Pediatr.
PD SEP
PY 2012
VL 33
IS 7
BP 535
EP 541
DI 10.1097/DBP.0b013e31825fd0af
PG 7
WC Behavioral Sciences; Psychology, Developmental; Pediatrics
SC Behavioral Sciences; Psychology; Pediatrics
GA 004GH
UT WOS:000308668400002
PM 22926660
ER
PT J
AU Buckley, JP
Palmieri, RT
Matuszewski, JM
Herring, AH
Baird, DD
Hartmann, KE
Hoppin, JA
AF Buckley, Jessie P.
Palmieri, Rachel T.
Matuszewski, Jeanine M.
Herring, Amy H.
Baird, Donna D.
Hartmann, Katherine E.
Hoppin, Jane A.
TI Consumer product exposures associated with urinary phthalate levels in
pregnant women
SO JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY
LA English
DT Article
DE phthalates; pregnancy; biomonitoring; urine; personal care products
ID NEW-YORK-CITY; DI-(2-ETHYLHEXYL) PHTHALATE; METABOLITE CONCENTRATIONS;
WAIST CIRCUMFERENCE; US POPULATION; CARE PRODUCTS; MONOESTERS;
VARIABILITY; OUTCOMES; SAMPLES
AB Human phthalate exposure is ubiquitous, but little is known regarding predictors of urinary phthalate levels. To explore this, 50 pregnant women aged 18-38 years completed two questionnaires on potential phthalate exposures and provided a first morning void. Urine samples were analyzed for 12 phthalate metabolites. Associations with questionnaire items were evaluated via Wilcoxon tests and t-tests, and r-squared values were calculated in multiple linear regression models. Few measured factors were statistically significantly associated with phthalate levels. Individuals who used nail polish had higher levels of mono-butyl phthalate (P=0.048) than non-users. Mono-benzyl phthalate levels were higher among women who used eye makeup (P=0.034) or used makeup on a regular basis (P=0.004). Women who used cologne or perfume had higher levels of di-(2-ethylhexyl) phthalate metabolites. Household products, home flooring or paneling, and other personal care products were also associated with urinary phthalates. The proportion of variance in metabolite concentrations explained by questionnaire items ranged between 0.31 for mono-ethyl phthalate and 0.42 for mono-n-methyl phthalate. Although personal care product use may be an important predictor of urinary phthalate levels, most of the variability in phthalate exposure was not captured by our relatively comprehensive set of questionnaire items.
C1 [Baird, Donna D.; Hoppin, Jane A.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Buckley, Jessie P.; Palmieri, Rachel T.; Hartmann, Katherine E.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Matuszewski, Jeanine M.; Herring, Amy H.] Univ N Carolina, Dept Biostat, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Herring, Amy H.] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA.
[Hartmann, Katherine E.] Vanderbilt Univ, Inst Med & Publ Hlth, Nashville, TN USA.
RP Hoppin, JA (reprint author), NIEHS, Epidemiol Branch, NIH, MD A3-05,POB 12233, Res Triangle Pk, NC 27709 USA.
EM hoppin1@niehs.nih.gov
RI Baird, Donna/D-5214-2017
OI Baird, Donna/0000-0002-5544-2653
FU National Institute of Environmental Health Sciences [T32 ES007018];
American Water Works Association Research Foundation [2579]; National
Institute of Environmental Health Sciences, NIH, DHHS [Z01ES049003]
FX Jessie P. Buckley and Jeanine M. Matuszewski were supported by a
National Institute of Environmental Health Sciences training grant (T32
ES007018). Amy H. Herring and Katherine E. Hartmann were supported by
the American Water Works Association Research Foundation under Contract
#2579. This work was supported in part by the Intramural Research
Program of the National Institute of Environmental Health Sciences, NIH,
DHHS (Z01ES049003). We thank CDC for the analysis of these samples.
NR 46
TC 39
Z9 41
U1 2
U2 37
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1559-0631
J9 J EXPO SCI ENV EPID
JI J. Expo. Sci. Environ. Epidemiol.
PD SEP-OCT
PY 2012
VL 22
IS 5
BP 468
EP 475
DI 10.1038/jes.2012.33
PG 8
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 994MD
UT WOS:000307934000006
PM 22760436
ER
PT J
AU Shroff, H
AF Shroff, H.
TI Faster and sharper: new technologies for imaging cells and embryos
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT 5th Special Conference of the International-Society-for-Neurochemistry
on Synapses and Dendritic Spines in Health and Disease
CY SEP 12-15, 2012
CL Buenos Aires, ARGENTINA
SP Int Soc Neurochem
C1 [Shroff, H.] Natl Inst Biomed Imaging & Bioengn, Sect High Resolut Imaging, NIH, Bethesda, MD USA.
RI Shroff, Hari/E-7247-2016
OI Shroff, Hari/0000-0003-3613-8215
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 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD SEP
PY 2012
VL 122
SU 1
SI SI
BP 8
EP 9
PG 2
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 003BI
UT WOS:000308582800028
ER
PT J
AU Russo, I
Caracciolo, L
Tweedie, D
Choi, SH
Greig, NH
Barlati, S
Bosetti, F
AF Russo, Isabella
Caracciolo, Luca
Tweedie, David
Choi, Sang-Ho
Greig, Nigel H.
Barlati, Sergio
Bosetti, Francesca
TI 3,6 '-Dithiothalidomide, a new TNF-alpha synthesis inhibitor, attenuates
the effect of A beta(1-42) intracerebroventricular injection on
hippocampal neurogenesis and memory deficit
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE 3; 6'-dithiothalidomide; A ss 1-42 peptide; Alzheimer's disease;
neurogenesis; neuroinflammation; TNF-a
ID TUMOR-NECROSIS-FACTOR; AMYLOID-BETA-PROTEIN; NEURAL STEM-CELLS;
ALZHEIMERS-DISEASE; MESSENGER-RNA; TRANSGENIC MICE; NEUROTROPHIC FACTOR;
COGNITIVE DEFICITS; IMPAIRS SURVIVAL; FACTOR RECEPTOR
AB J. Neurochem. (2012) 122, 11811192. Abstract Evidence indicates altered neurogenesis in neurodegenerative diseases associated with inflammation, including Alzheimers disease (AD). Neuroinflammation and its propagation have a critical role in the degeneration of hippocampal neurons, cognitive impairment, and altered neurogenesis. Particularly, tumor necrosis factor (TNF)-a plays a central role in initiating and regulating the cytokine cascade during an inflammatory response and is up-regulated in brain of AD patients. In this study, we investigated the effects of a novel thalidomide-based TNF-a lowering drug, 3,6'-dithiothalidomide, on hippocampal progenitor cell proliferation, neurogenesis and, memory tasks after intracerebroventricular injection of beta-amyloid (A beta)142 peptide. Seven days after A beta 142 injection, a significant proliferation of hippocampal progenitor cells and memory impairment were evident. Four weeks after A beta 142 peptide injection, elevated numbers of surviving 5-bromo-2'-deoxyuridine cells and newly formed neurons were detected. Treatment with 3,6'-dithiothalidomide attenuated these A beta 142 provoked effects. Our data indicate that although treatment with 3,6'-dithiothalidomide in part attenuated the increase in hippocampal neurogenesis caused by A beta 142-induced neuroinflammation, the drug prevented memory deficits associated with increased numbers of activated microglial cells and inflammatory response. Therefore, 3,6'-dithiothalidomide treatment likely reduced neuronal tissue damage induced by neuroinflammation following A beta 142 injection. Understanding the modulation of neurogenesis, and its relationship with memory function could open new therapeutic interventions for AD and other neurodegenerative disorders with an inflammatory component.
C1 [Russo, Isabella; Caracciolo, Luca; Choi, Sang-Ho; Bosetti, Francesca] NIA, Mol Neurosci Unit, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
[Russo, Isabella; Barlati, Sergio] Univ Brescia, Div Biol & Genet, Dept Biomed Sci & Biotechnol, Brescia, Italy.
[Russo, Isabella; Barlati, Sergio] Univ Brescia, Natl Inst Neurosci, Brescia, Italy.
[Tweedie, David; Greig, Nigel H.] NIA, Drug Design & Dev Sect, Lab Neurosci, NIH, Baltimore, MD 21224 USA.
RP Bosetti, F (reprint author), NINDS, NIH, 6001 Execut Blvd,Rm 2118, Bethesda, MD 20892 USA.
EM frances@mail.nih.gov
OI Russo, Isabella/0000-0002-6151-2451
FU Intramural Research Program of NIA; NIH; NEDD project Regione Lombardia
[14546-A SAL7]
FX This research was supported by the Intramural Research Program of NIA,
NIH and NEDD project Regione Lombardia (ID 14546-A SAL7). We thank
Henriette Van Praag for useful discussion, Catherine Spong and Daniel
Abebe for providing the Water Maze apparatus and for helpful technical
advice. The authors declare that they have no competing interests.
NR 73
TC 27
Z9 28
U1 2
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD SEP
PY 2012
VL 122
IS 6
BP 1181
EP 1192
DI 10.1111/j.1471-4159.2012.07846.x
PG 12
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 999EA
UT WOS:000308291000009
PM 22731394
ER
PT J
AU Johnson, B
Gay, M
Zhang, K
Neuberger, T
Horovitz, SG
Hallett, M
Sebastianelli, W
Slobounov, S
AF Johnson, Brian
Gay, Michael
Zhang, Kai
Neuberger, Thomas
Horovitz, Silvina G.
Hallett, Mark
Sebastianelli, Wayne
Slobounov, Semyon
TI The Use of Magnetic Resonance Spectroscopy in the Subacute Evaluation of
Athletes Recovering from Single and Multiple Mild Traumatic Brain Injury
SO JOURNAL OF NEUROTRAUMA
LA English
DT Article
DE concussion; H-1-MRS; MTBI; multiple MTBI
ID CORTICAL GRAY-MATTER; ACETYL-L-ASPARTATE; CORPUS-CALLOSUM; WHITE-MATTER;
MR SPECTROSCOPY; MITOCHONDRIAL BIOGENESIS; N-ACETYLASPARTATE; TEMPORAL
WINDOW; CONCUSSION; ABNORMALITIES
AB Advanced neuroimaging techniques have shown promise in highlighting the subtle changes and nuances in mild traumatic brain injury (MTBI) even though clinical assessment has shown a return to pre-injury levels. Here we use H-1-magnetic resonance spectroscopy (H-1-MRS) to evaluate the brain metabolites N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr) in the corpus callosum in MTBI. Specifically, we looked at the NAA/Cho, NAA/Cr, and Cho/Cr ratios in the genu and splenium. We recruited 20 normal volunteers (NV) and 28 student athletes recovering from the subacute phase of MTBI. The MTBI group was categorized based upon the number of MTBIs and time from injury to H-1-MRS evaluation. Significant reductions in NAA/Cho and NAA/Cr ratios were seen in the genu of the corpus callosum, but not in the splenium, for MTBI subjects, regardless of the number of MTBIs. MTBI subjects recovering from their first MTBI showed the greatest alteration in NAA/Cho and NAA/Cr ratios. Time since injury to H-1-MRS acquisition was based upon symptom resolution and did not turn out to be a significant factor. We observed that as the number of MTBIs increased, so did the length of time for symptom resolution. Unexpected findings from this study are that MTBI subjects showed a trend of increasing NAA/Cho and NAA/Cr ratios that coincided with increasing number of MTBIs.
C1 [Johnson, Brian; Gay, Michael; Zhang, Kai; Slobounov, Semyon] Penn State Univ, Dept Kinesiol, University Pk, PA 16802 USA.
[Johnson, Brian; Neuberger, Thomas] Penn State Univ, Dept Bioengn, University Pk, PA 16802 USA.
[Sebastianelli, Wayne; Slobounov, Semyon] Penn State Univ, Dept Orthopaed Surg & Rehabil, University Pk, PA 16802 USA.
[Horovitz, Silvina G.; Hallett, Mark; Slobounov, Semyon] NINDS, NIH, Bethesda, MD 20892 USA.
RP Slobounov, S (reprint author), Penn State Univ, Dept Kinesiol, 19 Recreat Bldg, University Pk, PA 16802 USA.
EM sms18@psu.edu
FU National Institutes of Health [RO1 NS056227-01A2]
FX This work was supported by National Institutes of Health Grant RO1
NS056227-01A2 "Identification of Athletes at Risk for Traumatic Brain
Injury."
NR 60
TC 20
Z9 20
U1 1
U2 11
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
J9 J NEUROTRAUM
JI J. Neurotrauma
PD SEP
PY 2012
VL 29
IS 13
BP 2297
EP 2304
DI 10.1089/neu.2011.2294
PG 8
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA 000PU
UT WOS:000308399900005
PM 22780855
ER
PT J
AU Yu, FS
Zhang, YM
Chuang, DM
AF Yu, Fengshan
Zhang, Yumin
Chuang, De-Maw
TI Lithium Reduces BACE1 Overexpression, Beta Amyloid Accumulation, and
Spatial Learning Deficits in Mice with Traumatic Brain Injury
SO JOURNAL OF NEUROTRAUMA
LA English
DT Article
DE beta amyloid; beta-APP-cleaving enzyme-1; learning and memory; lithium;
traumatic brain injury
ID GLYCOGEN-SYNTHASE KINASE-3; ALZHEIMERS-DISEASE; PRECURSOR PROTEIN;
NEUROTROPHIC FACTOR; CEREBROSPINAL-FLUID; MOUSE MODEL; PHOSPHORYLATION;
INHIBITION; EXPRESSION; INCREASES
AB Traumatic brain injury (TBI) leads to both acute injury and long-term neurodegeneration, and is a major risk factor for developing Alzheimer's disease (AD). Beta amyloid (A beta) peptide deposits in the brain are one of the pathological hallmarks of AD. A beta levels increase after TBI in animal models and in patients with head trauma, and reducing A beta levels after TBI has beneficial effects. Lithium is known to be neuroprotective in various models of neurodegenerative disease, and can reduce A beta generation by modulating glycogen synthase kinase-3 (GSK-3) activity. In this study we explored whether lithium would reduce A beta load after TBI, and improve learning and memory in a mouse TBI model. Lithium chloride (1.5 mEq/kg, IP) was administered 15 min after TBI, and once daily thereafter for up to 3 weeks. At 3 days after injury, lithium attenuated TBI-induced A beta load increases, amyloid precursor protein (APP) accumulation, and beta-APP-cleaving enzyme-1 (BACE1) overexpression in the corpus callosum and hippocampus. Increased Tau protein phosphorylation in the thalamus was also attenuated after lithium treatment following TBI at the same time point. Notably, lithium treatment significantly improved spatial learning and memory in the Y-maze test conducted 10 days after TBI, and in the Morris water maze test performed 17-20 days post-TBI, in association with increased hippocampal preservation. Thus post-insult treatment with lithium appears to alleviate the TBI-induced A beta load and consequently improves spatial memory. Our findings suggest that lithium is a potentially useful agent for managing memory impairments after TBI or other head trauma.
C1 [Yu, Fengshan; Chuang, De-Maw] NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
[Yu, Fengshan; Zhang, Yumin; Chuang, De-Maw] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA.
[Yu, Fengshan; 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 Department of Defense in the Center for Neuroscience and Regenerative
Medicine (CNRM); Blast Lethality Injury and Research Program; Intramural
Research Program of the National Institute of Mental Health, National
Institutes of Health (IRP-NIMH-NIH)
FX Support for this work included funding from the Department of Defense in
the Center for Neuroscience and Regenerative Medicine (CNRM), 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). We are grateful to Drs. Oz Malkesman and
Amanda Fu, and to Ms. Laura Tucker from the CNRM for assistance with the
behavioral tests and CCI surgery. We would like to thank Drs. Chi-Tso
Chiu and Zhifei Wang of the NIMH, and Dr. Flaubert Tchantchou from the
Uniformed Services University of the Health Sciences, for their helpful
discussions. The authors also wish to gratefully acknowledge the
editorial assistance of Peter Leeds and Ioline Henter of the NIMH.
NR 49
TC 32
Z9 32
U1 1
U2 6
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
J9 J NEUROTRAUM
JI J. Neurotrauma
PD SEP
PY 2012
VL 29
IS 13
BP 2342
EP 2351
DI 10.1089/neu.2012.2449
PG 10
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA 000PU
UT WOS:000308399900010
PM 22583494
ER
PT J
AU Tyson, JE
Pedroza, C
Langer, J
Green, C
Morris, B
Stevenson, D
Van Meurs, KP
Oh, W
Phelps, D
O'Shea, M
McDavid, GE
Grisby, C
Higgins, R
AF Tyson, J. E.
Pedroza, C.
Langer, J.
Green, C.
Morris, B.
Stevenson, D.
Van Meurs, K. P.
Oh, W.
Phelps, D.
O'Shea, M.
McDavid, G. E.
Grisby, C.
Higgins, R.
CA Eunice Kennedy Shriver Natl Inst
TI Does aggressive phototherapy increase mortality while decreasing
profound impairment among the smallest and sickest newborns?
SO JOURNAL OF PERINATOLOGY
LA English
DT Article
DE phototherapy; bilirubin; ELBW infant; randomized clinical trial;
statistical interaction; Bayesian analysis
ID LOW-BIRTH-WEIGHT; NEURODEVELOPMENTAL OUTCOMES; BAYESIAN METHODS;
CLINICAL-TRIALS; BILIRUBIN; INFANTS; ASSOCIATION; ANTIOXIDANT; CHILDREN;
PLASMA
AB Objective: Aggressive phototherapy (AgPT) is widely used and assumed to be safe and effective for even the most immature infants. We assessed whether the benefits and hazards for the smallest and sickest infants differed from those for other extremely low-birth-weight (ELBW; <= 1000g) infants in our Neonatal Research Network trial, the only large trial of AgPT.
Study Design: ELBW infants (n = 1974) were randomized to AgPT or conservative phototherapy at age 12 to 36 h. The effect of AgPT on outcomes (death, impairment, profound impairment, death or impairment (primary outcome), and death or profound impairment) at 18 to 22 months of corrected age was related to BW stratum (501 to 750 g; 751 to 1000 g) and baseline severity of illness using multilevel regression equations. The probability of benefit and of harm was directly assessed with Bayesian analyses.
Result: Baseline illness severity was well characterized using mechanical ventilation and FiO(2) at 24 h age. Among mechanically ventilated infants <= 750 g BW (n = 684), a reduction in impairment and in profound impairment was offset by higher mortality (P for interaction <0.05) with no significant effect on composite outcomes. Conservative Bayesian 1 analyses of this subgroup identified a 99% (posterior) probability that AgPT increased mortality, a 97% probability that AgPT reduced impairment, and a 99% probability that AgPT reduced profound impairment.
Conclusion: Findings from the only large trial of AgPT suggest that AgPT may increase mortality while reducing impairment and profound impairment among the smallest and sickest infants. New approaches to reduce their serum bilirubin need development and rigorous testing. Journal of Perinatology (2012) 32, 677-684; doi:10.1038/jp.2012.64; published online 31 May 2012
C1 [Tyson, J. E.; Pedroza, C.; Green, C.; McDavid, G. E.] Univ Texas Hlth Sci Ctr Houston, Dept Pediat, Houston, TX USA.
[Langer, J.] RTI Int, Res Triangle Pk, NC USA.
[Morris, B.] Trinity Mother Frances Hosp & Clin, Tyler, TX USA.
[Stevenson, D.; Van Meurs, K. P.] Stanford Univ, Palo Alto, CA 94304 USA.
[Oh, W.] Brown Univ, Providence, RI 02912 USA.
[Phelps, D.] Univ Rochester, Rochester, NY USA.
[O'Shea, M.] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Grisby, C.] Univ Cincinnati, Dept Pediat, Cincinnati, OH 45221 USA.
[Higgins, R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Tyson, JE (reprint author), Univ Texas Houston, Med Sch Houston, Dept Pediat, 6431 Fannin St,MSB 2-106, Houston, TX 77030 USA.
EM jon.e.tyson@uth.tmc.edu
FU National Institutes of Health; Eunice Kennedy Shriver National Institute
of Child Health and Human Development (NICHD) [ClinicalTrials.gov
NCT00114543]; Eunice Kennedy Shriver National Institute of Child Health
and Human Development, Natus Medical loaned light-emitting diode
phototherapy lights to each center
FX The National Institutes of Health and the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (NICHD)
provided grant support for the Neonatal Research Network's Phototherapy
Trial (ClinicalTrials.gov NCT00114543). Data collected at participating
sites of the NICHD Neonatal Research Network (NRN) were transmitted to
RTI International, the data coordinating center (DCC) for the network,
which stored, managed, and analyzed the data for this study. On behalf
of the NRN, Dr Abhik Das (DCC Principal Investigator) and Mr John Langer
(DCC Statistician) had full access to all the data in the study and take
responsibility for the integrity of the data and accuracy of the data
analysis. We are indebted to our medical and nursing colleagues and the
infants and their parents who agreed to take part in this study. This
study was supported by grants from the National Institutes of Health and
from the Eunice Kennedy Shriver National Institute of Child Health and
Human Development, Natus Medical loaned light-emitting diode
phototherapy lights to each center. These lights were used at the
discretion of the attending neonatologist in treating infants in either
treatment group. The lights were returned to Natus Medical or purchased
at a prorated price after the study. Natus Medical played no role in the
study design, data collection, data analysis, or manuscript preparation
or revision. The authors declare no other potential conflicts of
interest.
NR 39
TC 15
Z9 15
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0743-8346
J9 J PERINATOL
JI J. Perinatol.
PD SEP
PY 2012
VL 32
IS 9
BP 677
EP 684
DI 10.1038/jp.2012.64
PG 8
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 998ZD
UT WOS:000308278000006
PM 22652561
ER
PT J
AU de Gonzalez, AB
Apostoaei, AI
Veiga, LHS
Rajaraman, P
Thomas, BA
Hoffman, FO
Gilbert, E
Land, C
AF de Gonzalez, Amy Berrington
Apostoaei, A. Iulian
Veiga, Lene H. S.
Rajaraman, Preetha
Thomas, Brian A.
Hoffman, F. Owen
Gilbert, Ethel
Land, Charles
TI RadRAT: a radiation risk assessment tool for lifetime cancer risk
projection
SO JOURNAL OF RADIOLOGICAL PROTECTION
LA English
DT Article
ID ATOMIC-BOMB SURVIVORS; IONIZING-RADIATION; POOLED ANALYSIS;
TINEA-CAPITIS; EXPOSURE; COHORTS; TUMORS
AB Risk projection methods allow for timely assessment of the potential magnitude of radiation-related cancer risks following low-dose radiation exposures. The estimation of such risks directly through observational studies would generally require infeasibly large studies and long-term follow-up to achieve reasonable statistical power. We developed an online radiation risk assessment tool (RadRAT) which can be used to estimate the lifetime risk of radiation-related cancer with uncertainty intervals following a user-specified exposure history (https://irep.nci.nih.gov/radrat). The uncertainty intervals constitute a key component of the program because of the various assumptions that are involved in such calculations. The risk models used in RadRAT are broadly based on those developed by the BEIR VII committee for estimating lifetime risk following low-dose radiation exposure of the US population for eleven site-specific cancers. We developed new risk models for seven additional cancer sites, oral, oesophagus, gallbladder, pancreas, rectum, kidney and brain/central nervous system (CNS) cancers, using data from Japanese atomic bomb survivors. The lifetime risk estimates are slightly higher for RadRAT than for BEIR VII across all exposure ages mostly because the weighting of the excess relative risk and excess absolute risk models was conducted on an arithmetic rather than a logarithmic scale. The calculator can be used to estimate lifetime cancer risk from both uniform and non-uniform doses that are acute or chronic. It is most appropriate for low-LET radiation doses <1 Gy, and for individuals with life-expectancy and cancer rates similar to the general population in the US.
C1 [de Gonzalez, Amy Berrington; Gilbert, Ethel; Land, Charles] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Apostoaei, A. Iulian; Rajaraman, Preetha; Thomas, Brian A.; Hoffman, F. Owen] SENES Oak Ridge Inc, Oak Ridge, TN 37830 USA.
[Veiga, Lene H. S.] Brazilian Nucl Energy Commiss, Inst Radioprotect & Dosimetry, Rio De Janeiro, Brazil.
RP de Gonzalez, AB (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM berringtona@mail.nih.gov
FU NIH; National Cancer Institute [DCC-OD-12-900]; National Institute of
Allergy and Infectious Diseases
FX This study was supported in part by the Intramural Research Program of
the NIH and the National Cancer Institute and by the Intra-Agency
Agreement between the National Institute of Allergy and Infectious
Diseases and the National Cancer Institute (# DCC-OD-12-900).
NR 33
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U1 0
U2 5
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0952-4746
J9 J RADIOL PROT
JI J. Radiol. Prot.
PD SEP
PY 2012
VL 32
IS 3
BP 205
EP 222
DI 10.1088/0952-4746/32/3/205
PG 18
WC Environmental Sciences; Public, Environmental & Occupational Health;
Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
Imaging
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
GA 999XH
UT WOS:000308348500004
PM 22810503
ER
PT J
AU Fernald, DH
Dickinson, LM
Froshaug, DB
Balasubramanian, BA
Holtrop, JS
Krist, AH
Glasgow, RE
Green, LA
AF Fernald, Douglas H.
Dickinson, L. Miriam
Froshaug, Desiree B.
Balasubramanian, Bijal A.
Holtrop, Jodi Summers
Krist, Alex H.
Glasgow, Russell E.
Green, Larry A.
TI Improving Multiple Health Risk Behaviors in Primary Care: Lessons from
the Prescription for Health COmmon Measures, Better Outcomes (COMBO)
Study
SO JOURNAL OF THE AMERICAN BOARD OF FAMILY MEDICINE
LA English
DT Article
DE Alcohol Drinking; Crisis Intervention; Counseling; Diet; Health
Behavior; Physical Activity; Practice-Based Research; Practice-Based
Research Networks; Primary Health Care; Risk Behavior; Smoking
ID PHYSICAL-ACTIVITY QUESTIONNAIRE; CHANGE INTERVENTIONS; CHRONIC ILLNESS;
LIFE-STYLE; PREVALENCE; ADOLESCENT; MANAGEMENT; PROMOTION; MEDICINE;
TRIAL
AB Background: Four health behaviors-smoking, risky drinking, physical inactivity, and unhealthy diets-contribute substantially to health care burden and are common among primary care patients. However, there is insufficient evidence to recommend broadly brief interventions to address all 4 of these in frontline primary care. This study took advantage of a multinetwork initiative to reflect on health behavior outcomes and the challenges of using a common set of measures to assess health behavior-change strategies for multiple health behaviors in routine primary care practice.
Methods: Standardized, brief practical health behavior and quality of life measures used across 7 practice-based research networks (PBRNs) with independent primary care interventions in 54 primary care practices between August 2005 and December 2007 were analyzed. Mixed-effects longitudinal models assessed whether intervention patients improved diet, physical activity, smoking, alcohol consumption, and unhealthy days over time. Separate analyses were conducted for each intervention.
Results: Of 4463 adults, 2199 had follow-up data, and all available data were used in longitudinal analyses. Adjusting for age, race/ethnicity, education, and baseline body mass index where available, diet scores improved significantly in 5 of 7 networks (P < .02). Physical activity improved significantly in 2 networks but declined in one network (P < .024). The likelihood of being a current smoker was reduced in 2 of 5 networks (P < .0001), and average alcoholic drinks per day was reduced in 2 network s (P < .02). Participants reported fewer unhealthy days at follow-up in 3 of 7 networks (P < .01). Details of implementation and the limitations in instrumentation help contextualize these modest outcomes.
Conclusions: Although some patients in these 7 PBRNs improved in several health behaviors and quality of life, the strength of evidence for field-ready methods to address multiple health risk behaviors remains elusive. The use of common measures to assess changes in 4 unhealthy behaviors was achieved practically in PBRNs testing diverse strategies to improve behaviors; however, variations in implementation, instrumentation performance, and some features of study design overwhelmed potential cross-PBRN comparisons. For common measures to be useful for comparisons across practices or PBRNs, greater standardization of study designs and careful attention to practicable implementation strategies are necessary. (J Am Board Fam Med 2012;25:701-711.)
C1 [Fernald, Douglas H.; Dickinson, L. Miriam; Green, Larry A.] Univ Colorado, Dept Family Med, Aurora, CO USA.
[Froshaug, Desiree B.] Colorado Fdn Med Care, Englewood, CO USA.
[Balasubramanian, Bijal A.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Holtrop, Jodi Summers] Michigan State Univ, Dept Family Med, E Lansing, MI 48824 USA.
[Krist, Alex H.] Virginia Commonwealth Univ, Dept Family & Community Med, Richmond, VA 23284 USA.
[Glasgow, Russell E.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA.
RP Fernald, DH (reprint author), Mail Stop F496,12631 E 17th Ave,Room 3423, Aurora, CO 80045 USA.
EM doug.fernald@ucdenver.edu
FU The Robert Wood Johnson Foundation
FX Funding provided by The Robert Wood Johnson Foundation.
NR 34
TC 8
Z9 8
U1 6
U2 25
PU AMER BOARD FAMILY MEDICINE
PI LEXINGTON
PA 2228 YOUNG DR, LEXINGTON, KY 40505 USA
SN 1557-2625
J9 J AM BOARD FAM MED
JI J. Am. Board Fam. Med.
PD SEP-OCT
PY 2012
VL 25
IS 5
BP 701
EP 711
DI 10.3122/jabfm.2012.03.110057
PG 11
WC Primary Health Care; Medicine, General & Internal
SC General & Internal Medicine
GA 004QZ
UT WOS:000308697500019
PM 22956706
ER
PT J
AU Eggers, P
AF Eggers, Paul
TI Lifetime Risk of ESRD: A Meaningful Concept?
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Editorial Material
ID UNTREATED KIDNEY FAILURE; UNITED-STATES; DISEASE; ADULTS; OLDER
C1 NIDDK, Bethesda, MD 20892 USA.
RP Eggers, P (reprint author), NIDDK, Room 615,6707 Democracy Blvd, Bethesda, MD 20892 USA.
EM eggersp@extra.niddk.nih.gov
NR 14
TC 0
Z9 0
U1 0
U2 3
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD SEP
PY 2012
VL 23
IS 9
BP 1444
EP 1446
DI 10.1681/ASN.2012070733
PG 3
WC Urology & Nephrology
SC Urology & Nephrology
GA 005UM
UT WOS:000308775600004
PM 22878959
ER
PT J
AU Viboud, C
Simonsen, L
AF Viboud, Cecile
Simonsen, Lone
TI Global mortality of 2009 pandemic influenza A H1N1
SO LANCET INFECTIOUS DISEASES
LA English
DT Editorial Material
ID DEATHS; BURDEN
C1 [Viboud, Cecile; Simonsen, Lone] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Simonsen, Lone] George Washington Univ, Dept Global Hlth, Sch Publ Hlth & Hlth Serv, Washington, DC USA.
RP Viboud, C (reprint author), NIH, Fogarty Int Ctr, 16 Ctr Dr, Bethesda, MD 20892 USA.
EM viboudc@mail.nih.gov
OI Simonsen, Lone/0000-0003-1535-8526
NR 13
TC 18
Z9 18
U1 0
U2 6
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 2012
VL 12
IS 9
BP 651
EP 653
DI 10.1016/S1473-3099(12)70152-4
PG 3
WC Infectious Diseases
SC Infectious Diseases
GA 994FM
UT WOS:000307916300004
PM 22738892
ER
PT J
AU Dawood, FS
Iuliano, AD
Reed, C
Meltzer, MI
Shay, DK
Cheng, PY
Bandaranayake, D
Breiman, RF
Brooks, WA
Buchy, P
Feikin, DR
Fowler, KB
Gordon, A
Hien, NT
Horby, P
Huang, QS
Katz, MA
Krishnan, A
Lal, R
Montgomery, JM
Molbak, K
Pebody, R
Presanis, AM
Razuri, H
Steens, A
Tinoco, YO
Wallinga, J
Yu, HJ
Vong, S
Bresee, J
Widdowson, MA
AF Dawood, Fatimah S.
Iuliano, A. Danielle
Reed, Carrie
Meltzer, Martin I.
Shay, David K.
Cheng, Po-Yung
Bandaranayake, Don
Breiman, Robert F.
Brooks, W. Abdullah
Buchy, Philippe
Feikin, Daniel R.
Fowler, Karen B.
Gordon, Aubree
Nguyen Tran Hien
Horby, Peter
Huang, Q. Sue
Katz, Mark A.
Krishnan, Anand
Lal, Renu
Montgomery, Joel M.
Molbak, Kare
Pebody, Richard
Presanis, Anne M.
Razuri, Hugo
Steens, Anneke
Tinoco, Yeny O.
Wallinga, Jacco
Yu, Hongjie
Vong, Sirenda
Bresee, Joseph
Widdowson, Marc-Alain
TI Estimated global mortality associated with the first 12 months of 2009
pandemic influenza A H1N1 virus circulation: a modelling study
SO LANCET INFECTIOUS DISEASES
LA English
DT Article
ID SEASONAL INFLUENZA; UNITED-STATES; EXCESS MORTALITY; DEATHS; BURDEN;
A(H1N1); ENGLAND; SEROPREVALENCE; NETHERLANDS; ANTIBODIES
AB Background 18 500 laboratory-confirmed deaths caused by the 2009 pandemic influenza A H1N1 were reported worldwide for the period April, 2009, to August, 2010. This number is likely to be only a fraction of the true number of the deaths associated with 2009 pandemic influenza A H1N1. We aimed to estimate the global number of deaths during the first 12 months of virus circulation in each country.
Methods We calculated crude respiratory mortality rates associated with the 2009 pandemic influenza A H1N1 strain by age (0-17 years, 18-64 years, and >64 years) using the cumulative (12 months) virus-associated symptomatic attack rates from 12 countries and symptomatic case fatality ratios (sCFR) from five high-income countries. To adjust crude mortality rates for differences between countries in risk of death from influenza, we developed a respiratory mortality multiplier equal to the ratio of the median lower respiratory tract infection mortality rate in each WHO region mortality stratum to the median in countries with very low mortality. We calculated cardiovascular disease mortality rates associated with 2009 pandemic influenza A H1N1 infection with the ratio of excess deaths from cardiovascular and respiratory diseases during the pandemic in five countries and multiplied these values by the crude respiratory disease mortality rate associated with the virus. Respiratory and cardiovascular mortality rates associated with 2009 pandemic influenza A H1N1 were multiplied by age to calculate the number of associated deaths.
Findings We estimate that globally there were 201 200 respiratory deaths (range 105 700-395 600) with an additional 83 300 cardiovascular deaths (46000-179900) associated with 2009 pandemic influenza A H1N1. 80% of the respiratory and cardiovascular deaths were in people younger than 65 years and 51% occurred in southeast Asia and Africa.
Interpretation Our estimate of respiratory and cardiovascular mortality associated with the 2009 pandemic influenza A H1N1 was 15 times higher than reported laboratory-confirmed deaths. Although no estimates of sCFRs were available from Africa and southeast Asia, a disproportionate number of estimated pandemic deaths might have occurred in these regions. Therefore, efforts to prevent influenza need to effectively target these regions in future pandemics.
C1 [Dawood, Fatimah S.; Iuliano, A. Danielle; Reed, Carrie; Shay, David K.; Cheng, Po-Yung; Lal, Renu; Montgomery, Joel M.; Bresee, Joseph; Widdowson, Marc-Alain] Ctr Dis Control & Prevent, Influenza Div, Atlanta, GA 30333 USA.
[Meltzer, Martin I.] Ctr Dis Control & Prevent, Sci & Program Serv Branch, Div Preparedness & Emerging Infect, Atlanta, GA 30333 USA.
[Bandaranayake, Don; Huang, Q. Sue] Natl Ctr Biosecur & Infect Dis, Environm Sci & Res Inst, Upper Hutt, New Zealand.
[Breiman, Robert F.; Feikin, Daniel R.; Katz, Mark A.] Ctr Dis Control & Prevent, Global Dis Detect Div, Kenya Med Res Inst, Nairobi, Kenya.
[Brooks, W. Abdullah] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh.
[Brooks, W. Abdullah] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Buchy, Philippe] Natl Influenza Ctr, Phnom Penh, Cambodia.
[Fowler, Karen B.] Univ Alabama Birmingham, Birmingham, AL USA.
[Gordon, Aubree] Univ Calif Berkeley, Berkeley, CA 94720 USA.
[Gordon, Aubree] NIH, John E Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Nguyen Tran Hien] Natl Inst Hyg & Epidemiol, Hanoi, Vietnam.
[Horby, Peter] Univ Oxford, Clin Res Unit, Wellcome Trust Major Overseas Programme, Hanoi, Vietnam.
[Krishnan, Anand] All India Inst Med Sci, Ctr Community Med, New Delhi, India.
[Montgomery, Joel M.; Razuri, Hugo; Tinoco, Yeny O.] Naval Med Res Unit 6, Lima, Peru.
[Molbak, Kare] Statens Serum Inst, Dept Epidemiol, DK-2300 Copenhagen, Denmark.
[Pebody, Richard; Presanis, Anne M.] MRC, Biostat Unit, Cambridge CB2 2BW, England.
[Steens, Anneke; Wallinga, Jacco] Natl Inst Publ Hlth & Environm, Ctr Infect Dis Control, NL-3720 BA Bilthoven, Netherlands.
[Yu, Hongjie] Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China.
[Vong, Sirenda] Inst Pasteur, Phnom Penh, Cambodia.
RP Dawood, FS (reprint author), Ctr Dis Control & Prevent, Influenza Div, 1600 Clifton Rd,MS A-32, Atlanta, GA 30333 USA.
EM fdawood@cdc.gov; mwiddowson@cdc.gov
RI Razuri, Hugo/C-1542-2013; Horby, Peter/D-1585-2013;
OI Pebody, Richard/0000-0002-9069-2885; Razuri, Hugo/0000-0003-4571-5520;
Horby, Peter/0000-0002-9822-1586; Molbak, Kare/0000-0002-3100-4990;
Shay, David/0000-0001-9619-4820; Widdowson,
Marc-Alain/0000-0002-0682-6933; Wallinga, Jacco/0000-0003-1725-5627;
Steens, Anneke/0000-0002-7474-1149; Gordon, Aubree/0000-0002-9352-7877;
Krishnan, Anand/0000-0002-9173-7811
FU Medical Research Council [MC_U105260556]
NR 52
TC 300
Z9 315
U1 3
U2 48
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1473-3099
EI 1474-4457
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD SEP
PY 2012
VL 12
IS 9
BP 687
EP 695
DI 10.1016/S1473-3099(12)70121-4
PG 9
WC Infectious Diseases
SC Infectious Diseases
GA 994FM
UT WOS:000307916300024
PM 22738893
ER
PT J
AU Ho, M
Royston, I
Beck, A
AF Ho, Mitchell
Royston, Ivor
Beck, Alain
TI 2nd PEGS Annual Symposium on Antibodies for Cancer Therapy April 30-May
1, 2012, Boston, MA USA
SO MABS
LA English
DT Article
DE antibody-drug conjugates; biosimilars; biobetters; bispecific
antibodies; cetuximab/Erbitux; immunotoxins; monoclonal antibodies;
rituximab/Rituxan; tumor penetration; trastuzumab/Herceptin
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; B-CELL LYMPHOMA; PHASE-I TRIAL;
CHIMERIC-ANTIGEN-RECEPTOR; HUMAN MONOCLONAL-ANTIBODY; GROWTH-FACTOR
RECEPTOR; RECOMBINANT IMMUNOTOXIN; BREAST-CANCER; HUMAN HYBRIDOMAS;
STRUCTURAL BASIS
AB The 2nd Annual Antibodies for Cancer Therapy symposium, organized again by Cambridge Healthtech Institute as part of the Protein Engineering Summit, was held in Boston, USA from April 30th to May 1st, 2012. Since the approval of the first cancer antibody therapeutic, rituximab, 15 y ago, 11 have been approved for cancer therapy, although one, gemtuzumab ozogamicin, was withdrawn from the market. The first day of the symposium started with a historical review of early work for lymphomas and leukemias and the evolution from murine to human antibodies. The symposium discussed the current status and future perspectives of therapeutic antibodies in the biology of immunoglobulin, emerging research on biosimilars and biobetters, and engineering bispecific antibodies and antibody-drug conjugates. The tumor penetration session was focused on the understanding of antibody therapy using ex vivo tumor spheroids and the development of novel agents targeting epithelial junctions in solid tumors. The second day of the symposium discussed the development of new generation recombinant immunotoxins with low immunogenicity, construction of chimeric antigen receptors, and the proof-of-concept of 'photoimmunotherapy'. The preclinical and clinical session presented antibodies targeting Notch signaling and chemokine receptors. Finally, the symposium discussed emerging technologies and platforms for therapeutic antibody discovery.
C1 [Ho, Mitchell] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Royston, Ivor] Forward Ventures, San Diego, CA USA.
[Beck, Alain] Ctr Immunol Pierre Fabre, St Julien En Genevois, France.
RP Ho, M (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM homi@mail.nih.gov
RI Ho, Mitchell/F-5059-2015
FU National Institutes of Health, National Cancer Institute (NCI); Center
for Cancer Research
FX This work is supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute (NCI), and the
Center for Cancer Research. The authors thank Ira Pastan, Richard
Morgan, Adrian Wiestner, Hisataka Kobayashi and Christoph Rader (NCI),
Wayne A. Marasco (Harvard), Andre Lieber (University of Washington),
Timothy Hoey (OncoMed), David Hilbert (Zyngenia), and Jin-San Yoo
(PharmAbcine) for reading the manuscript. 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 have no conflict of interest directly relevant
to the content of this report.
NR 64
TC 6
Z9 7
U1 3
U2 12
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1942-0862
J9 MABS-AUSTIN
JI mAbs
PD SEP-OCT
PY 2012
VL 4
IS 5
BP 562
EP 570
DI 10.4161/mabs.21521
PG 9
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 000VJ
UT WOS:000308417700002
PM 22864478
ER
PT J
AU Phung, Y
Gao, W
Man, YG
Nagata, S
Ho, M
AF Phung, Yen
Gao, Wei
Man, Yan-Gao
Nagata, Satoshi
Ho, Mitchell
TI High-affinity monoclonal antibodies to cell surface tumor antigen
glypican-3 generated through a combination of peptide immunization and
flow cytometry screening
SO MABS
LA English
DT Article
DE hybridoma technology; heparan sulfate proteoglycans; flow cytometry;
high-throughput screening; cell-surface glycoproteins; hepatocellular
carcinoma; peptide immunization
ID HEPATOCELLULAR-CARCINOMA; LIVER-CANCER; MARKER; IDENTIFICATION;
IMMUNOTHERAPY; IMMUNOTOXIN; SERUM
AB Isolating high-affinity antibodies against native tumor antigens on the cell surface is not straightforward using standard hybridoma procedures. Here, we describe a combination method of synthetic peptide immunization and high-throughput flow cytometry screening to efficiently isolate hybridomas for cell binding. Using this method, we identified high-affinity monoclonal antibodies specific for the native form of glypcian-3 (GPC3), a target heterogeneously expressed in hepatocellular carcinoma (HCC) and other cancers. We isolated a panel of monoclonal antibodies (YP6, YP7, YP8, YP9 and YP9.1) for cell surface binding. The antibodies were used to characterize GPC3 protein expression in human liver cancer cell lines and tissues by flow cytometry, immunoblotting and immunohistochemistry. The best antibody (YP7) bound cell surface-associated GPC3 with equilibrium dissociation constant, K-D = 0.3 nmol/L and was highly specific for HCC, not normal tissues or other forms of primary liver cancers (such as cholangiocarcinoma). Interestingly, the new antibody was highly sensitive in that it detected GPC3 in low expression ovarian clear cell carcinoma and melanoma cells. The YP7 antibody exhibited significant HCC xenograft tumor growth inhibition in nude mice. These results describe an improved method for producing high-affinity monoclonal antibodies to cell surface tumor antigens and represent a general approach to isolate therapeutic antibodies against cancer. The new high-affinity antibodies described here have significant potential for GPC3-expressing cancer diagnostics and therapy.
C1 [Phung, Yen; Gao, Wei; Ho, Mitchell] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Man, Yan-Gao] Henry Jackson Fdn Adv Mil Med, Diagnost & Translat Res Ctr, Bethesda, MD USA.
[Nagata, Satoshi] Sanford Res USD, Canc Biol Res Ctr, Sioux Falls, SD USA.
RP Ho, M (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM homi@mail.nih.gov
RI Ho, Mitchell/F-5059-2015
FU National Institutes of Health, National Cancer Institute (NCI), Center
for Cancer Research; NIH COBRE grant [1P20RR024219-01A2]
FX This study was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute (NCI), Center
for Cancer Research. Satoshi Nagata was supported by a NIH COBRE grant
(1P20RR024219-01A2). We thank our colleagues Heungnam Kim for
establishing the A431/G1 cell line, Mingqian Feng and Ruoqi Wang for
producing recombinant GPC3 and GPC3 Delta HS proteins, and the NIH
Fellows Editorial Board for editorial assistance.
NR 23
TC 13
Z9 15
U1 3
U2 17
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1942-0862
J9 MABS-AUSTIN
JI mAbs
PD SEP-OCT
PY 2012
VL 4
IS 5
BP 592
EP 599
DI 10.4161/mabs.20933
PG 8
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 000VJ
UT WOS:000308417700006
PM 22820551
ER
PT J
AU Ristow, LC
Miller, HE
Padmore, LJ
Chettri, R
Salzman, N
Caimano, MJ
Rosa, PA
Coburn, J
AF Ristow, Laura C.
Miller, Halli E.
Padmore, Lavinia J.
Chettri, Rekha
Salzman, Nita
Caimano, Melissa J.
Rosa, Patricia A.
Coburn, Jenifer
TI The beta 3-integrin ligand of Borrelia burgdorferi is critical for
infection of mice but not ticks
SO MOLECULAR MICROBIOLOGY
LA English
DT Article
ID PSEUDOTUBERCULOSIS INVASIN PROTEIN; LYME-DISEASE SPIROCHETE;
OUTER-SURFACE PROTEIN; FIBRONECTIN-BINDING PROTEIN; TOLL-LIKE RECEPTORS;
YERSINIA-PSEUDOTUBERCULOSIS; MAMMALIAN INFECTION; IXODES-SCAPULARIS;
INTEGRIN LIGAND; COMPLEMENT RESISTANCE
AB P66 is a Borrelia burgdorferi surface protein with beta 3 integrin binding and channel forming activities. In this study, the role of P66 in mammalian and tick infection was examined. B. burgdorferi Delta p66 strains were not infectious in wild-type, TLR2-/-- or MyD88-/--deficient mice. Strains with p66 restored to the chromosome restored near wild-type infectivity, while complementation with p66 on a shuttle vector did not restore infectivity. Delta p66 mutants are cleared quickly from the site of inoculation, but analyses of cytokine expression and cellular infiltrates at the site of inoculation did not reveal a specific mechanism of clearance. The defect in these mutants cannot be attributed to nutrient limitation or an inability to adapt to the host environment in vivo as Delta p66 bacteria were able to survive as well as wild type in dialysis membrane chambers in the rat peritoneum.Delta p66 bacteria were able to survive in ticks through the larva to nymph moult, but were non-infectious in mice when delivered by tick bite. Independent lines of evidence do not support any increased susceptibility of the Delta p66 strains to factors in mammalian blood. This study is the first to define a B. burgdorferi adhesin as essential for mammalian, but not tick infection.
C1 [Ristow, Laura C.; Coburn, Jenifer] Med Coll Wisconsin, Grad Program Microbiol Immunol & Mol Genet, Milwaukee, WI 53226 USA.
[Miller, Halli E.; Padmore, Lavinia J.; Chettri, Rekha; Coburn, Jenifer] Med Coll Wisconsin, Dept Med, Div Infect Dis, Milwaukee, WI 53226 USA.
[Salzman, Nita] Med Coll Wisconsin, Dept Pediat, Div Gastroenterol, Milwaukee, WI 53226 USA.
[Caimano, Melissa J.] Univ Connecticut, Dept Med, Hlth Sci Ctr, Farmington, CT 06032 USA.
[Rosa, Patricia A.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, Hamilton, MT USA.
RP Coburn, J (reprint author), Med Coll Wisconsin, Grad Program Microbiol Immunol & Mol Genet, Milwaukee, WI 53226 USA.
EM jcoburn@mcw.edu
OI Salzman, Nita/0000-0003-0939-6139
FU NIH [AI051407, AI059505]; Advancing a Healthier Wisconsin programme,
Department of Medicine; Center for Infectious Disease Research at the
Medical College of Wisconsin
FX We thank Dr Dorothee Grimm and Angela Tanudra for their contributions to
constructing B. burgdorferi mutants and complemented clones, Dr Tom
Schwan and Dr Paul Policastro for their generosity in providing
training, advice and protocols for work with ticks, and Sheryl Konrad
for her contributions in optimizing qPCR conditions. PCR primer
sequences for plasmid profiling were generously provided by Dr Darrin
Akins. This work was supported by NIH Grants AI051407 and AI059505, the
Advancing a Healthier Wisconsin programme, Department of Medicine, and
the Center for Infectious Disease Research at the Medical College of
Wisconsin.
NR 75
TC 27
Z9 27
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0950-382X
J9 MOL MICROBIOL
JI Mol. Microbiol.
PD SEP
PY 2012
VL 85
IS 6
BP 1105
EP 1118
DI 10.1111/j.1365-2958.2012.08160.x
PG 14
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA 003BY
UT WOS:000308584400008
PM 22758390
ER
PT J
AU Morris, AP
Voight, BF
Teslovich, TM
Ferreira, T
Segre, AV
Steinthorsdottir, V
Strawbridge, RJ
Khan, H
Grallert, H
Mahajan, A
Prokopenko, I
Kang, HM
Dina, C
Esko, T
Fraser, RM
Kanoni, S
Kumar, A
Lagou, V
Langenberg, C
Luan, JA
Lindgren, CM
Muller-Nurasyid, M
Pechlivanis, S
Rayner, NW
Scott, LJ
Wiltshire, S
Yengo, L
Kinnunen, L
Rossin, EJ
Raychaudhuri, S
Johnson, AD
Dimas, AS
Loos, RJF
Vedantam, S
Chen, H
Florez, JC
Fox, C
Liu, CT
Rybin, D
Couper, DJ
Kao, WHL
Li, M
Cornelis, MC
Kraft, P
Sun, Q
van Dam, RM
Stringham, HM
Chines, PS
Fischer, K
Fontanillas, P
Holmen, OL
Hunt, SE
Jackson, AU
Kong, A
Lawrence, R
Meyer, J
Perry, JRB
Platou, CGP
Potter, S
Rehnberg, E
Robertson, N
Sivapalaratnam, S
Stancakova, A
Stirrups, K
Thorleifsson, G
Tikkanen, E
Wood, AR
Almgren, P
Atalay, M
Benediktsson, R
Bonnycastle, LL
Burtt, N
Carey, J
Charpentier, G
Crenshaw, AT
Doney, ASF
Dorkhan, M
Edkins, S
Emilsson, V
Eury, E
Forsen, T
Gertow, K
Gigante, B
Grant, GB
Groves, CJ
Guiducci, C
Herder, C
Hreidarsson, AB
Hui, JN
James, A
Jonsson, A
Rathmann, W
Klopp, N
Kravic, J
Krjutskov, K
Langford, C
Leander, K
Lindholm, E
Lobbens, S
Mannisto, S
Mirza, G
Muhleisen, TW
Musk, B
Parkin, M
Rallidis, L
Saramies, J
Sennblad, B
Shah, S
Sigurdsson, G
Silveira, A
Steinbach, G
Thorand, B
Trakalo, J
Veglia, F
Wennauer, R
Winckler, W
Zabaneh, D
Campbell, H
van Duijn, C
Uitterlinden, AG
Hofman, A
Sijbrands, E
Abecasis, GR
Owen, KR
Zeggini, E
Trip, MD
Forouhi, NG
Syvanen, AC
Eriksson, JG
Peltonen, L
Nothen, MM
Balkau, B
Palmer, CNA
Lyssenko, V
Tuomi, T
Isomaa, B
Hunter, DJ
Qi, L
Shuldiner, AR
Roden, M
Barroso, I
Wilsgaard, T
Beilby, J
Hovingh, K
Price, JF
Wilson, JF
Rauramaa, R
Lakka, TA
Lind, L
Dedoussis, G
Njolstad, I
Pedersen, NL
Khaw, KT
Wareham, NJ
Keinanen-Kiukaanniemi, SM
Saaristo, TE
Korpi-Hyovalti, E
Saltevo, J
Laakso, M
Kuusisto, J
Metspalu, A
Collins, FS
Mohlke, KL
Bergman, RN
Tuomilehto, J
Boehm, BO
Gieger, C
Hveem, K
Cauchi, S
Froguel, P
Baldassarre, D
Tremoli, E
Humphries, SE
Saleheen, D
Danesh, J
Ingelsson, E
Ripatti, S
Salomaa, V
Erbel, R
Jockel, KH
Moebus, S
Peters, A
Illig, T
de Faire, U
Hamsten, A
Morris, AD
Donnelly, PJ
Frayling, TM
Hattersley, AT
Boerwinkle, E
Melander, O
Kathiresan, S
Nilsson, PM
Deloukas, P
Thorsteinsdottir, U
Groop, LC
Stefansson, K
Hu, F
Pankow, JS
Dupuis, J
Meigs, JB
Altshuler, D
Boehnke, M
McCarthy, MI
AF Morris, Andrew P.
Voight, Benjamin F.
Teslovich, Tanya M.
Ferreira, Teresa
Segre, Ayellet V.
Steinthorsdottir, Valgerdur
Strawbridge, Rona J.
Khan, Hassan
Grallert, Harald
Mahajan, Anubha
Prokopenko, Inga
Kang, Hyun Min
Dina, Christian
Esko, Tonu
Fraser, Ross M.
Kanoni, Stavroula
Kumar, Ashish
Lagou, Vasiliki
Langenberg, Claudia
Luan, Jian'an
Lindgren, Cecilia M.
Mueller-Nurasyid, Martina
Pechlivanis, Sonali
Rayner, N. William
Scott, Laura J.
Wiltshire, Steven
Yengo, Loic
Kinnunen, Leena
Rossin, Elizabeth J.
Raychaudhuri, Soumya
Johnson, Andrew D.
Dimas, Antigone S.
Loos, Ruth J. F.
Vedantam, Sailaja
Chen, Han
Florez, Jose C.
Fox, Caroline
Liu, Ching-Ti
Rybin, Denis
Couper, David J.
Kao, Wen Hong L.
Li, Man
Cornelis, Marilyn C.
Kraft, Peter
Sun, Qi
van Dam, Rob M.
Stringham, Heather M.
Chines, Peter S.
Fischer, Krista
Fontanillas, Pierre
Holmen, Oddgeir L.
Hunt, Sarah E.
Jackson, Anne U.
Kong, Augustine
Lawrence, Robert
Meyer, Julia
Perry, John R. B.
Platou, Carl G. P.
Potter, Simon
Rehnberg, Emil
Robertson, Neil
Sivapalaratnam, Suthesh
Stancakova, Alena
Stirrups, Kathleen
Thorleifsson, Gudmar
Tikkanen, Emmi
Wood, Andrew R.
Almgren, Peter
Atalay, Mustafa
Benediktsson, Rafn
Bonnycastle, Lori L.
Burtt, Noel
Carey, Jason
Charpentier, Guillaume
Crenshaw, Andrew T.
Doney, Alex S. F.
Dorkhan, Mozhgan
Edkins, Sarah
Emilsson, Valur
Eury, Elodie
Forsen, Tom
Gertow, Karl
Gigante, Bruna
Grant, George B.
Groves, Christopher J.
Guiducci, Candace
Herder, Christian
Hreidarsson, Astradur B.
Hui, Jennie
James, Alan
Jonsson, Anna
Rathmann, Wolfgang
Klopp, Norman
Kravic, Jasmina
Krjutskov, Kaarel
Langford, Cordelia
Leander, Karin
Lindholm, Eero
Lobbens, Stephane
Mannisto, Satu
Mirza, Ghazala
Muehleisen, Thomas W.
Musk, Bill
Parkin, Melissa
Rallidis, Loukianos
Saramies, Jouko
Sennblad, Bengt
Shah, Sonia
Sigurdsson, Gunnar
Silveira, Angela
Steinbach, Gerald
Thorand, Barbara
Trakalo, Joseph
Veglia, Fabrizio
Wennauer, Roman
Winckler, Wendy
Zabaneh, Delilah
Campbell, Harry
van Duijn, Cornelia
Uitterlinden, Andre G.
Hofman, Albert
Sijbrands, Eric
Abecasis, Goncalo R.
Owen, Katharine R.
Zeggini, Eleftheria
Trip, Mieke D.
Forouhi, Nita G.
Syvanen, Ann-Christine
Eriksson, Johan G.
Peltonen, Leena
Noethen, Markus M.
Balkau, Beverley
Palmer, Colin N. A.
Lyssenko, Valeriya
Tuomi, Tiinamaija
Isomaa, Bo
Hunter, David J.
Qi, Lu
Shuldiner, Alan R.
Roden, Michael
Barroso, Ines
Wilsgaard, Tom
Beilby, John
Hovingh, Kees
Price, Jackie F.
Wilson, James F.
Rauramaa, Rainer
Lakka, Timo A.
Lind, Lars
Dedoussis, George
Njolstad, Inger
Pedersen, Nancy L.
Khaw, Kay-Tee
Wareham, Nicholas J.
Keinanen-Kiukaanniemi, Sirkka M.
Saaristo, Timo E.
Korpi-Hyovalti, Eeva
Saltevo, Juha
Laakso, Markku
Kuusisto, Johanna
Metspalu, Andres
Collins, Francis S.
Mohlke, Karen L.
Bergman, Richard N.
Tuomilehto, Jaakko
Boehm, Bernhard O.
Gieger, Christian
Hveem, Kristian
Cauchi, Stephane
Froguel, Philippe
Baldassarre, Damiano
Tremoli, Elena
Humphries, Steve E.
Saleheen, Danish
Danesh, John
Ingelsson, Erik
Ripatti, Samuli
Salomaa, Veikko
Erbel, Raimund
Joeckel, Karl-Heinz
Moebus, Susanne
Peters, Annette
Illig, Thomas
de Faire, Ulf
Hamsten, Anders
Morris, Andrew D.
Donnelly, Peter J.
Frayling, Timothy M.
Hattersley, Andrew T.
Boerwinkle, Eric
Melander, Olle
Kathiresan, Sekar
Nilsson, Peter M.
Deloukas, Panos
Thorsteinsdottir, Unnur
Groop, Leif C.
Stefansson, Kari
Hu, Frank
Pankow, James S.
Dupuis, Josee
Meigs, James B.
Altshuler, David
Boehnke, Michael
McCarthy, Mark I.
CA Wellcome Trust Case Control
Meta-Anal Glucose Insulin-Related
Genetic Invest ANthropometric
Asian Genetic Epidemiology
S Asian Type 2 Diabet SAT2D
DIAbet Genetics Replication
TI Large-scale association analysis provides insights into the genetic
architecture and pathophysiology of type 2 diabetes
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; INSULIN-RESISTANCE; COMMON
VARIANTS; METAANALYSIS; RISK; EXPRESSION; SNPS; MAP; INDIVIDUALS
AB To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genomewide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signaling and cell cycle regulation, in diabetes pathogenesis.
C1 [Morris, Andrew P.; Ferreira, Teresa; Mahajan, Anubha; Prokopenko, Inga; Kumar, Ashish; Lagou, Vasiliki; Lindgren, Cecilia M.; Rayner, N. William; Wiltshire, Steven; Dimas, Antigone S.; Perry, John R. B.; Robertson, Neil; Mirza, Ghazala; Trakalo, Joseph; Donnelly, Peter J.; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Voight, Benjamin F.; Segre, Ayellet V.; Rossin, Elizabeth J.; Raychaudhuri, Soumya; Fontanillas, Pierre; Burtt, Noel; Carey, Jason; Crenshaw, Andrew T.; Grant, George B.; Guiducci, Candace; Parkin, Melissa; Winckler, Wendy; Kathiresan, Sekar; Altshuler, David] Broad Inst Harvard & Massachusetts Inst Technol M, Cambridge, MA USA.
[Voight, Benjamin F.] Univ Penn, Perelman Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA.
[Teslovich, Tanya M.; Kang, Hyun Min; Scott, Laura J.; Stringham, Heather M.; Jackson, Anne U.; Abecasis, Goncalo R.; Boehnke, Michael] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
[Segre, Ayellet V.; Rossin, Elizabeth J.; Florez, Jose C.; Kathiresan, Sekar; Altshuler, David] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Segre, Ayellet V.; Florez, Jose C.; Meigs, James B.; Altshuler, David] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Steinthorsdottir, Valgerdur; Kong, Augustine; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Stefansson, Kari] deCODE Genet, Reykjavik, Iceland.
[Strawbridge, Rona J.; Gertow, Karl; Sennblad, Bengt; Silveira, Angela; Hamsten, Anders] Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Stockholm, Sweden.
[Strawbridge, Rona J.; Gertow, Karl; Sennblad, Bengt; Silveira, Angela; Hamsten, Anders] Karolinska Univ Hosp Solna, Ctr Mol Med, Stockholm, Sweden.
[Khan, Hassan; Khaw, Kay-Tee; Saleheen, Danish; Danesh, John] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
[Grallert, Harald; Klopp, Norman; Illig, Thomas] Helmholtz Zentrum Muenchen, Res Unit Mol Epidemiol, Neuherberg, Germany.
[Prokopenko, Inga; Rayner, N. William; Robertson, Neil; Groves, Christopher J.; Owen, Katharine R.; McCarthy, Mark I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
[Dina, Christian] INSERM, UMR 1087, Nantes, France.
[Dina, Christian] CNRS, UMR 6291, Nantes, France.
[Dina, Christian] Univ Nantes, Dept Biol Med & Hlth, Nantes, France.
[Esko, Tonu; Fischer, Krista; Krjutskov, Kaarel; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.
[Esko, Tonu; Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia.
[Fraser, Ross M.; Campbell, Harry; Price, Jackie F.; Wilson, James F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
[Kanoni, Stavroula; Hunt, Sarah E.; Potter, Simon; Stirrups, Kathleen; Edkins, Sarah; Langford, Cordelia; Zeggini, Eleftheria; Barroso, Ines; Ripatti, Samuli; Deloukas, Panos] Wellcome Trust Sanger Inst, Cambridge, England.
[Langenberg, Claudia; Luan, Jian'an; Loos, Ruth J. F.; Forouhi, Nita G.; Wareham, Nicholas J.] Addenbrookes Hosp, Inst Metab Sci, Med Res Council MRC Epidemiol Unit, Cambridge, England.
[Mueller-Nurasyid, Martina] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
[Mueller-Nurasyid, Martina; Meyer, Julia; Gieger, Christian] Helmholtz Zentrum Muenchen, Inst Genet Epidemiol, Neuherberg, Germany.
[Mueller-Nurasyid, Martina] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany.
[Pechlivanis, Sonali; Joeckel, Karl-Heinz; Moebus, Susanne] Univ Duisburg Essen, Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany.
[Yengo, Loic; Eury, Elodie; Lobbens, Stephane; Cauchi, Stephane; Froguel, Philippe] Inst Pasteur, CNRS, UMR 8199, Inst Biol, F-59019 Lille, France.
[Yengo, Loic; Eury, Elodie; Lobbens, Stephane; Cauchi, Stephane; Froguel, Philippe] Univ Lille 2, Inst Pasteur, Lille, France.
[Yengo, Loic] Univ Lille 1, Model Data Anal & Learning MODAL Team, Inst Natl Rech Informat & Automat INRIA Lille Nor, Math Lab,CNRS,UMR 8524, Lille, France.
[Kinnunen, Leena; Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland.
[Rossin, Elizabeth J.] Harvard Univ, Hlth Sci & Technol MD Program, Boston, MA 02115 USA.
[Rossin, Elizabeth J.] MIT, Boston, MA USA.
[Rossin, Elizabeth J.] Harvard Univ, Harvard Biol & Biomed Sci Program, Boston, MA 02115 USA.
[Raychaudhuri, Soumya] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA.
[Raychaudhuri, Soumya] Partners Ctr Personalized Genom Med, Boston, MA USA.
[Johnson, Andrew D.; Fox, Caroline; Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Dimas, Antigone S.] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland.
[Dimas, Antigone S.] Biomed Sci Res Ctr Al Fleming, Vari, Greece.
[Loos, Ruth J. F.] Mt Sinai Sch Med, Charles R Bronfman Inst Personalized Med, New York, NY USA.
[Loos, Ruth J. F.] Mt Sinai Sch Med, Child Hlth & Dev Inst, New York, NY USA.
[Loos, Ruth J. F.] Mt Sinai Sch Med, Dept Prevent Med, New York, NY USA.
[Vedantam, Sailaja; Florez, Jose C.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
[Vedantam, Sailaja] Childrens Hosp, Div Genet & Endocrinol, Boston, MA 02115 USA.
[Chen, Han; Liu, Ching-Ti; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA.
[Fox, Caroline] Brigham & Womens Hosp, Div Endocrinol & Metab, Boston, MA 02115 USA.
[Rybin, Denis] Boston Univ, Data Coordinating Ctr, Boston, MA 02215 USA.
[Couper, David J.] Univ N Carolina, Dept Biostat, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA.
[Kao, Wen Hong L.; Li, Man] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Cornelis, Marilyn C.; Kraft, Peter; Sun, Qi; van Dam, Rob M.; Hunter, David J.; Qi, Lu; Hu, Frank] Harvard Univ, Sch Publ Hlth, Dept Nutr & Epidemiol, Boston, MA 02115 USA.
[Kraft, Peter; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA.
[Sun, Qi; Hunter, David J.; Qi, Lu; Hu, Frank] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[van Dam, Rob M.] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore.
[Chines, Peter S.; Bonnycastle, Lori L.; Collins, Francis S.] NHGRI, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Holmen, Oddgeir L.; Platou, Carl G. P.; Hveem, Kristian] Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, Nord Trondelag Hlth Study HUNT Res Ctr, Levanger, Norway.
[Lawrence, Robert] Univ Western Australia, Ctr Genet Epidemiol & Biostat, Nedlands, WA 6009, Australia.
[Perry, John R. B.; Wood, Andrew R.; Frayling, Timothy M.] Univ Exeter, Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter, Devon, England.
[Platou, Carl G. P.] Nord Trondelag Hlth Trust, Levanger Hosp, Dept Internal Med, Levanger, Norway.
[Rehnberg, Emil; Pedersen, Nancy L.; Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Sivapalaratnam, Suthesh; Trip, Mieke D.; Hovingh, Kees] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands.
[Stancakova, Alena; Laakso, Markku; Kuusisto, Johanna] Univ Eastern Finland, Dept Med, Kuopio, Finland.
[Stancakova, Alena; Laakso, Markku; Kuusisto, Johanna] Kuopio Univ Hosp, SF-70210 Kuopio, Finland.
[Tikkanen, Emmi; Ripatti, Samuli] Inst Mol Med Finland FIMM, Helsinki, Finland.
[Tikkanen, Emmi; Mannisto, Satu; Eriksson, Johan G.; Ripatti, Samuli; Salomaa, Veikko] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Almgren, Peter; Dorkhan, Mozhgan; Jonsson, Anna; Kravic, Jasmina; Lindholm, Eero; Lyssenko, Valeriya; Melander, Olle; Nilsson, Peter M.; Groop, Leif C.] Lund Univ, Scania Univ Hosp, Ctr Diabet, Dept Clin Sci Malmo, Malmo, Sweden.
[Atalay, Mustafa; Lakka, Timo A.] Univ Eastern Finland, Inst Biomed, Kuopio, Finland.
[Benediktsson, Rafn; Thorsteinsdottir, Unnur; Stefansson, Kari] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Benediktsson, Rafn; Hreidarsson, Astradur B.; Sigurdsson, Gunnar] Landspitali Univ Hosp, Dept Endocrinol & Metab, Reykjavik, Iceland.
[Charpentier, Guillaume] Corbeil Essonnes Hosp, Endocrinol Diabetol Unit, Corbeil Essonnes, France.
[Doney, Alex S. F.; Palmer, Colin N. A.; Morris, Andrew D.] Univ Dundee, Ninewells Hosp, Biomed Res Inst, Diabet Res Ctr, Dundee, Scotland.
[Doney, Alex S. F.; Palmer, Colin N. A.; Morris, Andrew D.] Univ Dundee, Ninewells Hosp, Biomed Res Inst, Pharmacogen Ctr, Dundee, Scotland.
[Emilsson, Valur; Sigurdsson, Gunnar] Iceland Heart Assoc, Kopavogur, Iceland.
[Forsen, Tom; Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.
[Forsen, Tom] Vaasa Hlth Care Ctr, Vaasa, Finland.
[Gigante, Bruna; Leander, Karin; de Faire, Ulf] Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, S-10401 Stockholm, Sweden.
[Herder, Christian; Roden, Michael] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, D-40225 Dusseldorf, Germany.
[Hui, Jennie; James, Alan; Musk, Bill; Beilby, John] Sir Charles Gairdner Hosp, Busselton Populat Med Res Inst, Nedlands, WA 6009, Australia.
[Hui, Jennie; Beilby, John] Queen Elizabeth II Med Ctr, PathW Lab Med Western Australia, Nedlands, WA, Australia.
[Hui, Jennie; Beilby, John] Univ Western Australia, Sch Pathol & Lab Med, Nedlands, WA 6009, Australia.
[Hui, Jennie; Musk, Bill] Univ Western Australia, Sch Populat Hlth, Nedlands, WA 6009, Australia.
[James, Alan] Queen Elizabeth II Med Ctr, W Australian Sleep Disorders Res Inst, Dept Pulm Physiol & Sleep Med, Nedlands, WA, Australia.
[James, Alan; Musk, Bill] Univ Western Australia, Sch Med & Pharmacol, Nedlands, WA 6009, Australia.
[Rathmann, Wolfgang] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Biometr & Epidemiol, D-40225 Dusseldorf, Germany.
[Muehleisen, Thomas W.; Noethen, Markus M.] Univ Bonn, Inst Human Genet, Bonn, Germany.
[Muehleisen, Thomas W.; Noethen, Markus M.] Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany.
[Rallidis, Loukianos] Univ Gen Hosp Attikon, Dept Cardiol, Athens, Greece.
[Saramies, Jouko] S Karelia Cent Hosp, Lappeenranta, Finland.
[Shah, Sonia; Zabaneh, Delilah] UCL, Genet Inst, Dept Genet Evolut & Environm, London, England.
[Steinbach, Gerald; Wennauer, Roman] Univ Ulm, Dept Clin Chem, Ulm, Germany.
[Steinbach, Gerald; Wennauer, Roman] Univ Ulm, Cent Lab, Ulm, Germany.
[Thorand, Barbara; Peters, Annette] Helmholtz Zentrum Muenchen, Inst Epidemiol 2, Neuherberg, Germany.
[Veglia, Fabrizio; Baldassarre, Damiano; Tremoli, Elena] IRCCS, Ctr Cardiol Monzino, Milan, Italy.
[Campbell, Harry; Wilson, James F.] Univ Edinburgh, Western Gen Hosp, MRC Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.
[van Duijn, Cornelia; Uitterlinden, Andre G.; Hofman, Albert] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
[van Duijn, Cornelia; Uitterlinden, Andre G.] Netherlands Consortium Hlth Ageing, Netherland Genom Initiat, Rotterdam, Netherlands.
[van Duijn, Cornelia; Uitterlinden, Andre G.] Ctr Med Syst Biol, Rotterdam, Netherlands.
[Uitterlinden, Andre G.; Sijbrands, Eric] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands.
[Owen, Katharine R.; McCarthy, Mark I.] Churchill Hosp, Oxford Natl Inst Hlth Res, Biomed Res Ctr, Oxford OX3 7LJ, England.
[Syvanen, Ann-Christine] Uppsala Univ, Dept Med Sci, Uppsala, Sweden.
[Eriksson, Johan G.] Univ Helsinki, Gen Hosp, Unit Gen Practice, Helsinki, Finland.
[Eriksson, Johan G.; Tuomi, Tiinamaija; Isomaa, Bo] Folkhalsan Res Ctr, Helsinki, Finland.
[Balkau, Beverley] INSERM CESP U1018, Villejuif, France.
[Balkau, Beverley] Univ Paris 11, UMRS 1018, Villejuif, France.
[Tuomi, Tiinamaija] Univ Helsinki, Helsinki Univ Hosp, Dept Med, Helsinki, Finland.
[Isomaa, Bo] Dept Social Serv & Hlth Care, Pietarsaari, Finland.
[Shuldiner, Alan R.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
[Shuldiner, Alan R.] Baltimore Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Baltimore, MD USA.
[Shuldiner, Alan R.] Univ Maryland, Sch Med, Program Personalized & Genom Med, Baltimore, MD 21201 USA.
[Roden, Michael] Univ Dusseldorf, Dept Med Metab Dis, D-40225 Dusseldorf, Germany.
[Barroso, Ines] Univ Cambridge, Addenbrookes Hosp, Metab Res Labs, Inst Metab Sci, Cambridge CB2 2QQ, England.
[Barroso, Ines] Addenbrookes Hosp, Inst Metab Sci, Cambridge Biomed Res Ctr, NIHR, Cambridge, England.
[Wilsgaard, Tom; Njolstad, Inger] Univ Tromso, Fac Hlth Sci, Dept Community Med, Tromso, Norway.
[Rauramaa, Rainer; Lakka, Timo A.] Kuopio Res Inst Exercise Med, Kuopio, Finland.
[Rauramaa, Rainer] Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, SF-70210 Kuopio, Finland.
[Lind, Lars] Uppsala Univ, Akad Sjukhuset, Dept Med Sci, Uppsala, Sweden.
[Dedoussis, George] Harokopio Univ, Dept Dietet Nutr, Athens, Greece.
[Keinanen-Kiukaanniemi, Sirkka M.] Univ Oulu, Inst Hlth Sci, Fac Med, Oulu, Finland.
[Keinanen-Kiukaanniemi, Sirkka M.] Oulu Univ Hosp, Unit Gen Practice, Oulu, Finland.
[Saaristo, Timo E.] Finnish Diabet Assoc, Tampere, Finland.
[Saaristo, Timo E.] Pirkanmaa Hosp Dist, Tampere, Finland.
[Korpi-Hyovalti, Eeva; Tuomilehto, Jaakko] S Ostrobothnia Cent Hosp, Dept Internal Med, Seinajoki, Finland.
[Saltevo, Juha] Cent Finland Cent Hosp, Dept Med, Jyvaskyla, Finland.
[Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Bergman, Richard N.] Cedars Sinai Med Ctr, Diabet & Obes Res Inst, Los Angeles, CA 90048 USA.
[Tuomilehto, Jaakko] Hosp Univ La Paz, Red RECAVA Grp RD06 0014 0015, Madrid, Spain.
[Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria.
[Boehm, Bernhard O.] Univ Med Ctr Ulm, Dept Internal Med, Div Endocrinol & Diabet, Ulm, Germany.
[Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London, England.
[Baldassarre, Damiano; Tremoli, Elena] Univ Milan, Dept Pharmacol Sci, Milan, Italy.
[Humphries, Steve E.] UCL, Inst Cardiovasc Sci, London, England.
[Saleheen, Danish] Ctr Noncommunicable Dis Pakistan, Karachi, Pakistan.
[Erbel, Raimund] Univ Duisburg Essen, Univ Hosp Essen, W German Heart Ctr, Clin Cardiol, Essen, Germany.
[Illig, Thomas] Hannover Med Sch, Hannover Unified Biobank, D-3000 Hannover, Germany.
[Donnelly, Peter J.] Univ Oxford, Dept Stat, Oxford OX1 3TG, England.
[Hattersley, Andrew T.] Univ Exeter, Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter, Devon, England.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA.
[Boerwinkle, Eric] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Altshuler, David] Harvard Univ, Sch Med, Dept Mol Biol, Boston, MA USA.
RP Morris, AP (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
EM amorris@well.ox.ac.uk; boehnke@umich.edu; mark.mccarthy@drl.ox.ac.uk
RI Grallert, Harald/B-3424-2013; Khan, Hassan/D-6267-2013; Abecasis,
Goncalo/B-7840-2010; Johnson, Andrew/G-6520-2013; Altshuler,
David/A-4476-2009; Lagou, Vasiliki/N-8451-2013; van Dam,
Rob/F-9674-2010; Strawbridge, Rona/H-5422-2012; Dina,
Christian/D-3535-2015; Gigante, Bruna/I-9252-2012; Palmer,
Colin/C-7053-2008; Fraser, Ross/J-9519-2012; Deloukas,
Panos/B-2922-2013; Boehm, Bernhard/F-8750-2015; Krjutskov,
Kaarel/H-8401-2015; Ripatti, Samuli/H-9446-2014; Wilson, James
F/A-5704-2009; Prokopenko, Inga/H-3241-2014; Thorand,
Barbara/B-5349-2014; Peters, Annette/A-6117-2011; Veglia,
Fabrizio/K-1958-2016; kinnunen, leena/B-7059-2012; Study,
GoDARTS/K-9448-2016; Leander, Karin/C-7261-2017; Yengo,
Loic/D-2692-2017; Baldassarre, Damiano/J-3295-2016
OI Forouhi, Nita/0000-0002-5041-248X; Chen, Han/0000-0002-9510-4923;
Nothen, Markus/0000-0002-8770-2464; Tuomi,
Tiinamaija/0000-0002-8306-6202; Eriksson, Johan/0000-0002-2516-2060;
Pankow, James/0000-0001-7076-483X; Hattersley,
Andrew/0000-0001-5620-473X; Esko, Tonu/0000-0003-1982-6569; Zeggini,
Eleftheria/0000-0003-4238-659X; Mannisto, Satu/0000-0002-8668-3046;
Lakka, Timo/0000-0002-9199-2871; Dupuis, Josee/0000-0003-2871-3603;
Humphries, Stephen E/0000-0002-8221-6547; Gieger,
Christian/0000-0001-6986-9554; Altshuler, David/0000-0002-7250-4107; van
Dam, Rob/0000-0002-7354-8734; Strawbridge, Rona/0000-0001-8506-3585;
Dina, Christian/0000-0002-7722-7348; Palmer, Colin/0000-0002-6415-6560;
Fraser, Ross/0000-0003-0488-2592; Deloukas, Panos/0000-0001-9251-070X;
Rybin, Denis/0000-0002-3657-4829; Kumar, Ashish/0000-0002-7075-5930;
Sijbrands, Eric/0000-0001-8857-7389; TREMOLI, ELENA/0000-0002-0929-6106;
Hunt, Sarah/0000-0002-8350-1235; Abecasis, Goncalo/0000-0003-1509-1825;
Krjutskov, Kaarel/0000-0003-1297-1464; Ripatti,
Samuli/0000-0002-0504-1202; Wilson, James F/0000-0001-5751-9178;
Prokopenko, Inga/0000-0003-1624-7457; Thorand,
Barbara/0000-0002-8416-6440; Veglia, Fabrizio/0000-0002-9378-8874;
kinnunen, leena/0000-0001-8739-4812; Leander, Karin/0000-0002-1404-9222;
Yengo, Loic/0000-0002-4272-9305; Baldassarre,
Damiano/0000-0002-2766-8882
FU Academy of Finland [77299, 102318, 110413, 118065, 123885, 124243,
129680, 129293, 129494, 136895, 139635, 141005, 213506, 251217]; Agence
Nationale de la Recherche (France); American Diabetes Association
[7-08-MN-OK]; Association Francaise des Diabetiques; Association de
Langue Francaise pour l'Etude du Diabete et des Maladies Metaboliques
(France); Association Diabete Risque Vasculaire (France); British
Diabetic Association (BDA) Research (UK); British Heart Foundation
[RG/98002, RG2008/08]; Cancer Research UK; Central Norway Health
Authority; Central Finland Hospital District; Center for Inherited
Disease Research (CIDR) (USA); Chief Scientist Office, Scotland
[CZB/4/672]; City of Kuopio (Finland); City of Leutkirch (Germany);
Department of Health (UK); Deutsche Forschungsgemeinschaft [ER1 55/6-2];
Diabetes UK; Doris Duke Charitable Foundation (USA); Estonian government
[SF0180142s0]; European Commission: ENGAGE [HEALTH-F4-2007-201413];
EXGENESIS [LSHM-CT-2004-005272, 245536, QLG1-CT-2002-00896, 2004310];
European Commission (Marie Curie: FP7-PEOPLE-IEF); European Regional
Development Fund; Faculty of Medicine at the Norwegian University of
Science and Technology; Finnish Diabetes Association; Finnish Diabetes
Research Foundation; Finnish Foundation for Cardiovascular Research;
Finnish Heart Association; Folkhalsan Research Foundation (Finland);
Food Standards Agency (UK); Foundation for Life and Health in Finland;
Federal Ministry of Education and Research (BMBF) (Germany); Federal
Ministry of Health (Germany); General Secretary of Research and
Technology (Greece); German Center for Diabetes Research (DZD); German
Research Council [GRK 1041]; Great Wine Estates of the Margaret River
region of Western Australia; Groupe d'Etude des Maladies Metaboliques et
Systemiques (France); Harvard Medical School (USA); Heinz Nixdorf
Foundation (Germany); Helmholtz Zentrum Munchen-Research Center for
Environment and Health (Germany); Helsinki University Central Hospital
Research Foundation (Finland); IngaBritt and Arne Lundberg's Research
Foundation (Sweden) [359]; Ministry of Health (Ricerca Corrente)
(Italy); Karolinska Institutet (Sweden); Knut and Alice Wallenberg
Foundation (Sweden) [KAW 2009.0243]; Kuopio University Hospital
(Finland); Municipal Heath Care Center and Hospital, Jakobstad, Finland;
Ministry of Social Affairs and Health (Finland); Ministry of Education
and Culture (Finland) [627]; Ministry of Innovation, Science, Research
and Technology of North Rhine-Westphalia (Germany); Medical Research
Council (UK) [G0000649, G0601261]; MRC-GSK pilot programme grant (UK);
Munich Center of Health Sciences (MC Health) (Germany); National Genome
Research Network (NGFN) (Germany); National Heart, Lung, and Blood
Institute (NHLBI) [HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641,
R01HL59367, R01HL086694, N01HC25195, N02HL64278]; National Human Genome
Research Institute (NHGRI) [U01HG004402, N01HG65403]; US National
Institutes of Health (USA) [HHSN268200625226C, UL1RR025005, U01HG004399,
1R21NS064908, 1Z01HG000024, AG028555, AG08724, AG04563, AG10175,
AG08861, CA055075]; National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK) [DK062370, DK058845, DK072193, DK078616,
DK080140, DK073490]; Narpes Health Care Foundation (Finland); National
Health Screening Service of Norway; National Institute of Health
Research (UK); National Institute for Health and Welfare (Finland);
Nord-Trondelag County Council (Norway); Nordic Center of Excellence in
Disease Genetics; Norwegian Institute of Public Health; Norwegian
Research Council; Novo Nordisk Fonden (Denmark); Ollqvist Foundation
(Sweden); Oxford NIHR Biomedical Research Centre (UK); Paavo Nurmi
Foundation (Finland); Paivikki and Sakari Sohlberg Foundation (Finland);
Perklen Foundation (Sweden); Pfizer; Pirkanmaa Hospital District
(Finland); Programme National de Recherche sur le Diabete (France);
Programme Hospitalier de Recherche Clinique (French Ministry of Health);
Region of Nord-Pas-de-Calais (Contrat de Projets Etat-Region) (France);
Research into Ageing (UK); Robert Dawson Evans Endowment of the
Department of Medicine at Boston University School of Medicine and
Boston Medical Center; Royal Swedish Academy of Sciences; Sarstedt AG
Co. (Germany); Signe and Ane Gyllenberg Foundation (Sweden); Slottery
Machine Association (Finland); Social Insurance Institution of Finland
[4/26/2010]; South OstroBothnia Hospital District (Finland); State of
Baden-Wurttemberg, Germany; Stockholm County Council [560183, 562183];
Stroke Association (UK); Swedish Research Council [8691, 09533,
2009-1039, Dnr 521-2010-3490, Dnr 521-2007-4037, Dnr 521-2008-2974, Dnr
825-2010-5983, Dnr 349-2008-6589]; Swedish Cultural Foundation in
Finland; Swedish Diabetes Foundation; Swedish Heart-Lung Foundation;
Swedish Foundation for Strategic Research; Swedish Society of Medicine;
Swedish Research Council; Swedish Research Council for Infrastructures;
Sigrid Juselius Foundation (Finland); Torsten and Ragnar Sderberg
Foundation (Sweden) [MT33/09]; University Hospital Essen (Germany);
University of Tromso (Norway); Uppsala University (Sweden); Uppsala
University Hospital (Sweden); Wellcome Trust [GR072960, 076113, 077016,
081682, 083948, 083270, 084711, 086596, 090367, 090532, 098051]
FX Funding for this study was provided by the Academy of Finland (77299,
102318, 110413, 118065, 123885, 124243, 129680, 129293, 129494, 136895,
139635, 141005, 213506 and 251217); Agence Nationale de la Recherche
(France); the American Diabetes Association (7-08-MN-OK); Association
Francaise des Diabetiques; Association de Langue Francaise pour l'Etude
du Diabete et des Maladies Metaboliques (France); Association Diabete
Risque Vasculaire (France); British Diabetic Association (BDA) Research
(UK); the British Heart Foundation (RG/98002 and RG2008/08); Cancer
Research UK; the Central Norway Health Authority; the Central Finland
Hospital District; the Center for Inherited Disease Research (CIDR)
(USA); the Chief Scientist Office, Scotland (CZB/4/672); the City of
Kuopio (Finland); the City of Leutkirch (Germany); the Department of
Health (UK); Deutsche Forschungsgemeinschaft (ER1 55/6-2); Diabetes UK;
the Doris Duke Charitable Foundation (USA); the Estonian government
(SF0180142s0); the European Commission: ENGAGE (HEALTH-F4-2007-201413),
EXGENESIS (LSHM-CT-2004-005272), 245536, QLG1-CT-2002-00896 and 2004310;
the European Commission (Marie Curie: FP7-PEOPLE-2010-IEF); the European
Regional Development Fund; the Faculty of Medicine at the Norwegian
University of Science and Technology; the Finnish Diabetes Association;
the Finnish Diabetes Research Foundation; the Finnish Foundation for
Cardiovascular Research; the Finnish Heart Association; the Finnish
Medical Society; the Folkhalsan Research Foundation (Finland); the Food
Standards Agency (UK); the Foundation for Life and Health in Finland;
the Federal Ministry of Education and Research (BMBF) (Germany); the
Federal Ministry of Health (Germany); the General Secretary of Research
and Technology (Greece); the German Center for Diabetes Research (DZD);
the German Research Council (GRK 1041); the Great Wine Estates of the
Margaret River region of Western Australia; Groupe d'Etude des Maladies
Metaboliques et Systemiques (France); Harvard Medical School (USA); the
Heinz Nixdorf Foundation (Germany); Helmholtz Zentrum Munchen-Research
Center for Environment and Health (Germany); the Helsinki University
Central Hospital Research Foundation (Finland); IngaBritt and Arne
Lundberg's Research Foundation (Sweden) (grant 359); the Ministry of
Health (Ricerca Corrente) (Italy); Karolinska Institutet (Sweden); the
Knut and Alice Wallenberg Foundation (Sweden) (KAW 2009.; 0243); Kuopio
University Hospital (Finland); the Municipal Heath Care Center and
Hospital, Jakobstad, Finland; the Ministry of Social Affairs and Health
(Finland); the Ministry of Education and Culture (Finland) (627;
2004-2011); the Ministry of Innovation, Science, Research and Technology
of North Rhine-Westphalia (Germany); the Medical Research Council (UK)
(G0000649 and G0601261); an MRC-GSK pilot programme grant (UK); the
Munich Center of Health Sciences (MC Health) (Germany); the National
Genome Research Network (NGFN) (Germany); the National Heart, Lung, and
Blood Institute (NHLBI) (HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641,
R01HL59367, R01HL086694, N01HC25195 and N02HL64278); the National Human
Genome Research Institute (NHGRI) (U01HG004402 and N01HG65403); the US
National Institutes of Health (USA) (HHSN268200625226C, UL1RR025005,
U01HG004399, 1R21NS064908, 1Z01HG000024, AG028555, AG08724, AG04563,
AG10175, AG08861 and CA055075); the National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK) (DK062370, DK058845, DK072193,
DK078616, DK080140 and DK073490); the Narpes Health Care Foundation
(Finland); the National Health Screening Service of Norway; the National
Institute of Health Research (UK); the National Institute for Health and
Welfare (Finland); the Nord-Trondelag County Council (Norway); the
Nordic Center of Excellence in Disease Genetics; the Norwegian Institute
of Public Health; the Norwegian Research Council; Novo Nordisk Fonden
(Denmark); the Ollqvist Foundation (Sweden); the Oxford NIHR Biomedical
Research Centre (UK); the Paavo Nurmi Foundation (Finland); the Paivikki
and Sakari Sohlberg Foundation (Finland); the Perklen Foundation
(Sweden); Pfizer; the Pirkanmaa Hospital District (Finland); Programme
National de Recherche sur le Diabete (France); Programme Hospitalier de
Recherche Clinique (French Ministry of Health); the Region of
Nord-Pas-de-Calais (Contrat de Projets Etat-Region) (France); Research
into Ageing (UK); the Robert Dawson Evans Endowment of the Department of
Medicine at Boston University School of Medicine and Boston Medical
Center; the Royal Swedish Academy of Sciences; Sarstedt AG & Co.
(Germany); the Signe and Ane Gyllenberg Foundation (Sweden); the
Slottery Machine Association (Finland); the Social Insurance Institution
of Finland (4/26/2010); the South OstroBothnia Hospital District
(Finland); the State of Baden-Wurttemberg, Germany; the Stockholm County
Council (560183 and 562183); Stroke Association (UK); the Swedish
Research Council (8691, 09533, 2009-1039, Dnr 521-2010-3490, Dnr
521-2007-4037, Dnr 521-2008-2974, Dnr 825-2010-5983 and Dnr
349-2008-6589); the Swedish Cultural Foundation in Finland; the Swedish
Diabetes Foundation; the Swedish Heart-Lung Foundation; the Swedish
Foundation for Strategic Research; the Swedish Society of Medicine; the
Swedish Research Council; the Swedish Research Council for
Infrastructures; The Sigrid Juselius Foundation (Finland); the Torsten
and Ragnar Sderberg Foundation (Sweden) (MT33/09); University Hospital
Essen (Germany); University of Tromso (Norway); Uppsala University
(Sweden); Uppsala University Hospital (Sweden); and the Wellcome Trust
(GR072960, 076113, 077016, 081682, 083948, 083270, 084711, 086596,
090367, 090532 and 098051).
NR 55
TC 626
Z9 633
U1 12
U2 140
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
EI 1546-1718
J9 NAT GENET
JI Nature Genet.
PD SEP
PY 2012
VL 44
IS 9
BP 981
EP +
DI 10.1038/ng.2383
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA 001WP
UT WOS:000308491200009
PM 22885922
ER
PT J
AU Scott, RA
Lagou, V
Welch, RP
Wheeler, E
Montasser, ME
Luan, JA
Magi, R
Strawbridge, RJ
Rehnberg, E
Gustafsson, S
Kanoni, S
Rasmussen-Torvik, LJ
Yengo, L
Lecoeur, C
Shungin, D
Sanna, S
Sidore, C
Johnson, PCD
Jukema, JW
Johnson, T
Mahajan, A
Verweij, N
Thorleifsson, G
Hottenga, JJ
Shah, S
Smith, AV
Sennblad, B
Gieger, C
Salo, P
Perola, M
Timpson, NJ
Evans, DM
St Pourcain, B
Wu, Y
Andrews, JS
Hui, JN
Bielak, LF
Zhao, W
Horikoshi, M
Navarro, P
Isaacs, A
O'Connell, JR
Stirrups, K
Vitart, V
Hayward, C
Esko, T
Mihailov, E
Fraser, RM
Fall, T
Voight, BF
Raychaudhuri, S
Chen, H
Lindgren, CM
Morris, AP
Rayner, NW
Robertson, N
Rybin, D
Liu, CT
Beckmann, JS
Willems, SM
Chines, PS
Jackson, AU
Kang, HM
Stringham, HM
Song, KJ
Tanaka, T
Peden, JF
Goel, A
Hicks, AA
An, P
Muller-Nurasyid, M
Franco-Cereceda, A
Folkersen, L
Marullo, L
Jansen, H
Oldehinkel, AJ
Bruinenberg, M
Pankow, JS
Kari, EN
Forouhi, NG
Loos, RJF
Edkins, S
Varga, TV
Hallmans, G
Oksa, H
Antonella, M
Nagaraja, R
Trompet, S
Ford, I
Bakker, SJL
Kong, A
Kumari, M
Gigante, B
Herder, C
Munroe, PB
Caulfield, M
Antti, J
Mangino, M
Small, K
Miljkovic, I
Liu, YM
Atalay, M
Kiess, W
James, AL
Rivadeneira, F
Uitterlinden, AG
Palmer, CNA
Doney, ASF
Willemsen, G
Smit, JH
Campbell, S
Polasek, O
Bonnycastle, LL
Hercberg, S
Dimitriou, M
Bolton, JL
Fowkes, GR
Kovacs, P
Lindstrom, J
Zemunik, T
Bandinelli, S
Wild, SH
Basart, HV
Rathmann, W
Grallert, H
Maerz, W
Kleber, ME
Boehm, BO
Peters, A
Pramstaller, PP
Province, MA
Borecki, IB
Hastie, ND
Rudan, I
Campbell, H
Watkins, H
Farrall, M
Stumvoll, M
Ferrucci, L
Waterworth, DM
Bergman, RN
Collins, FS
Tuomilehto, J
Watanabe, RM
de Geus, EJC
Penninx, BW
Hofman, A
Oostra, BA
Psaty, BM
Vollenweider, P
Wilson, JF
Wright, AF
Hovingh, GK
Metspalu, A
Uusitupa, M
Magnusson, PKE
Kyvik, KO
Kaprio, J
Price, JF
Dedoussis, GV
Deloukas, P
Meneton, P
Lind, L
Boehnke, M
Shuldiner, AR
van Duijn, CM
Morris, AD
Toenjes, A
Peyser, PA
Beilby, JP
Korner, A
Kuusisto, J
Laakso, M
Bornstein, SR
Schwarz, PEH
Lakka, TA
Rauramaa, R
Adair, LS
Smith, GD
Spector, TD
Illig, T
de Faire, U
Hamsten, A
Gudnason, V
Kivimaki, M
Hingorani, A
Keinanen-Kiukaanniemi, SM
Saaristo, TE
Boomsma, DI
Stefansson, K
van der Harst, P
Dupuis, J
Pedersen, NL
Sattar, N
Harris, TB
Cucca, F
Ripatti, S
Salomaa, V
Mohlke, KL
Balkau, B
Froguel, P
Pouta, A
Jarvelin, MR
Wareham, NJ
Bouatia-Naji, N
McCarthy, MI
Franks, PW
Meigs, JB
Teslovich, TM
Florez, JC
Langenberg, C
Ingelsson, E
Prokopenko, I
Barroso, I
AF Scott, Robert A.
Lagou, Vasiliki
Welch, Ryan P.
Wheeler, Eleanor
Montasser, May E.
Luan, Jian'an
Maegi, Reedik
Strawbridge, Rona J.
Rehnberg, Emil
Gustafsson, Stefan
Kanoni, Stavroula
Rasmussen-Torvik, Laura J.
Yengo, Loic
Lecoeur, Cecile
Shungin, Dmitry
Sanna, Serena
Sidore, Carlo
Johnson, Paul C. D.
Jukema, J. Wouter
Johnson, Toby
Mahajan, Anubha
Verweij, Niek
Thorleifsson, Gudmar
Hottenga, Jouke-Jan
Shah, Sonia
Smith, Albert V.
Sennblad, Bengt
Gieger, Christian
Salo, Perttu
Perola, Markus
Timpson, Nicholas J.
Evans, David M.
St Pourcain, Beate
Wu, Ying
Andrews, Jeanette S.
Hui, Jennie
Bielak, Lawrence F.
Zhao, Wei
Horikoshi, Momoko
Navarro, Pau
Isaacs, Aaron
O'Connell, Jeffrey R.
Stirrups, Kathleen
Vitart, Veronique
Hayward, Caroline
Esko, Tonu
Mihailov, Evelin
Fraser, Ross M.
Fall, Tove
Voight, Benjamin F.
Raychaudhuri, Soumya
Chen, Han
Lindgren, Cecilia M.
Morris, Andrew P.
Rayner, Nigel W.
Robertson, Neil
Rybin, Denis
Liu, Ching-Ti
Beckmann, Jacques S.
Willems, Sara M.
Chines, Peter S.
Jackson, Anne U.
Kang, Hyun Min
Stringham, Heather M.
Song, Kijoung
Tanaka, Toshiko
Peden, John F.
Goel, Anuj
Hicks, Andrew A.
An, Ping
Mueller-Nurasyid, Martina
Franco-Cereceda, Anders
Folkersen, Lasse
Marullo, Letizia
Jansen, Hanneke
Oldehinkel, Albertine J.
Bruinenberg, Marcel
Pankow, James S.
North, Kari E.
Forouhi, Nita G.
Loos, Ruth J. F.
Edkins, Sarah
Varga, Tibor V.
Hallmans, Goeran
Oksa, Heikki
Antonella, Mulas
Nagaraja, Ramaiah
Trompet, Stella
Ford, Ian
Bakker, Stephan J. L.
Kong, Augustine
Kumari, Meena
Gigante, Bruna
Herder, Christian
Munroe, Patricia B.
Caulfield, Mark
Antti, Jula
Mangino, Massimo
Small, Kerrin
Miljkovic, Iva
Liu, Yongmei
Atalay, Mustafa
Kiess, Wieland
James, Alan L.
Rivadeneira, Fernando
Uitterlinden, Andre G.
Palmer, Colin N. A.
Doney, Alex S. F.
Willemsen, Gonneke
Smit, Johannes H.
Campbell, Susan
Polasek, Ozren
Bonnycastle, Lori L.
Hercberg, Serge
Dimitriou, Maria
Bolton, Jennifer L.
Fowkes, Gerard R.
Kovacs, Peter
Lindstrom, Jaana
Zemunik, Tatijana
Bandinelli, Stefania
Wild, Sarah H.
Basart, Hanneke V.
Rathmann, Wolfgang
Grallert, Harald
Maerz, Winfried
Kleber, Marcus E.
Boehm, Bernhard O.
Peters, Annette
Pramstaller, Peter P.
Province, Michael A.
Borecki, Ingrid B.
Hastie, Nicholas D.
Rudan, Igor
Campbell, Harry
Watkins, Hugh
Farrall, Martin
Stumvoll, Michael
Ferrucci, Luigi
Waterworth, Dawn M.
Bergman, Richard N.
Collins, Francis S.
Tuomilehto, Jaakko
Watanabe, Richard M.
de Geus, Eco J. C.
Penninx, Brenda W.
Hofman, Albert
Oostra, Ben A.
Psaty, Bruce M.
Vollenweider, Peter
Wilson, James F.
Wright, Alan F.
Hovingh, G. Kees
Metspalu, Andres
Uusitupa, Matti
Magnusson, Patrik K. E.
Kyvik, Kirsten O.
Kaprio, Jaakko
Price, Jackie F.
Dedoussis, George V.
Deloukas, Panos
Meneton, Pierre
Lind, Lars
Boehnke, Michael
Shuldiner, Alan R.
van Duijn, Cornelia M.
Morris, Andrew D.
Toenjes, Anke
Peyser, Patricia A.
Beilby, John P.
Koerner, Antje
Kuusisto, Johanna
Laakso, Markku
Bornstein, Stefan R.
Schwarz, Peter E. H.
Lakka, Timo A.
Rauramaa, Rainer
Adair, Linda S.
Smith, George Davey
Spector, Tim D.
Illig, Thomas
de Faire, Ulf
Hamsten, Anders
Gudnason, Vilmundur
Kivimaki, Mika
Hingorani, Aroon
Keinanen-Kiukaanniemi, Sirkka M.
Saaristo, Timo E.
Boomsma, Dorret I.
Stefansson, Kari
van der Harst, Pim
Dupuis, Josee
Pedersen, Nancy L.
Sattar, Naveed
Harris, Tamara B.
Cucca, Francesco
Ripatti, Samuli
Salomaa, Veikko
Mohlke, Karen L.
Balkau, Beverley
Froguel, Philippe
Pouta, Anneli
Jarvelin, Marjo-Riitta
Wareham, Nicholas J.
Bouatia-Naji, Nabila
McCarthy, Mark I.
Franks, Paul W.
Meigs, James B.
Teslovich, Tanya M.
Florez, Jose C.
Langenberg, Claudia
Ingelsson, Erik
Prokopenko, Inga
Barroso, Ines
CA DIAbet Genetics Replication
TI Large-scale association analyses identify new loci influencing glycemic
traits and provide insight into the underlying biological pathways
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; BODY-MASS INDEX; KLOTHO GENE POLYMORPHISMS;
BINDING-PROTEIN-ALPHA; INSULIN-RESISTANCE; GLUCOSE-METABOLISM;
SUSCEPTIBILITY LOCI; KAPPA-B; CARDIOVASCULAR-DISEASE; SKELETAL-MUSCLE
AB Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.
C1 [Meigs, James B.; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Scott, Robert A.; Luan, Jian'an; Forouhi, Nita G.; Loos, Ruth J. F.; Wareham, Nicholas J.; Langenberg, Claudia] Addenbrookes Hosp, Inst Metab Sci, Med Res Council MRC Epidemiol Unit, Cambridge, England.
[Lagou, Vasiliki; Maegi, Reedik; Mahajan, Anubha; Horikoshi, Momoko; Lindgren, Cecilia M.; Morris, Andrew P.; Rayner, Nigel W.; Robertson, Neil; Peden, John F.; Goel, Anuj; Marullo, Letizia; Watkins, Hugh; Farrall, Martin; McCarthy, Mark I.; Prokopenko, Inga] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Lagou, Vasiliki; Horikoshi, Momoko; Rayner, Nigel W.; Robertson, Neil; McCarthy, Mark I.; Prokopenko, Inga] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
[Welch, Ryan P.] Univ Michigan, Sch Med, Bioinformat Grad Program, Ann Arbor, MI USA.
[Welch, Ryan P.; Sidore, Carlo; Jackson, Anne U.; Kang, Hyun Min; Stringham, Heather M.; Boehnke, Michael; Teslovich, Tanya M.] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Welch, Ryan P.; Sidore, Carlo; Jackson, Anne U.; Kang, Hyun Min; Stringham, Heather M.; Boehnke, Michael; Teslovich, Tanya M.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
[Wheeler, Eleanor; Kanoni, Stavroula; Stirrups, Kathleen; Edkins, Sarah; Deloukas, Panos; Barroso, Ines] Wellcome Trust Sanger Inst, Cambridge, England.
[Montasser, May E.; O'Connell, Jeffrey R.; Shuldiner, Alan R.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
[Maegi, Reedik; Perola, Markus; Esko, Tonu; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.
[Strawbridge, Rona J.; Sennblad, Bengt; Folkersen, Lasse; Hamsten, Anders] Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Stockholm, Sweden.
[Strawbridge, Rona J.; Folkersen, Lasse; Hamsten, Anders] Karolinska Univ Hosp, Ctr Mol Med, Stockholm, Sweden.
[Rehnberg, Emil; Gustafsson, Stefan; Fall, Tove; Magnusson, Patrik K. E.; Pedersen, Nancy L.; Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Rasmussen-Torvik, Laura J.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
[Yengo, Loic; Lecoeur, Cecile; Froguel, Philippe; Bouatia-Naji, Nabila] Univ Lille Nord France, Lille, France.
[Yengo, Loic; Lecoeur, Cecile; Froguel, Philippe; Bouatia-Naji, Nabila] Inst Pasteur, CNRS, UMR 8199, F-59019 Lille, France.
[Shungin, Dmitry; Varga, Tibor V.; Franks, Paul W.] Lund Univ, Dept Clin Sci, Skane Univ Hosp Malmo, Genet & Mol Epidemiol Unit, Malmo, Sweden.
[Shungin, Dmitry; Franks, Paul W.] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
[Shungin, Dmitry] Umea Univ, Dept Odontol, Umea, Sweden.
[Sanna, Serena; Sidore, Carlo; Antonella, Mulas; Cucca, Francesco] CNR, Ist Ric Genet & Biomed, Monserrato, Italy.
[Sidore, Carlo; Cucca, Francesco] Univ Sassari, Dipartimento Sci Biomed, I-07100 Sassari, Italy.
[Johnson, Paul C. D.; Ford, Ian] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
[Jukema, J. Wouter; Trompet, Stella] Durrer Ctr Cardiogenet Res, ICIN, Utrecht, Netherlands.
[Jukema, J. Wouter; Trompet, Stella] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.
[Johnson, Toby; Munroe, Patricia B.; Caulfield, Mark] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, Dept Clin Pharmacol, London, England.
[Johnson, Toby; Munroe, Patricia B.; Caulfield, Mark] Queen Mary Univ London, Barts & London Sch Med & Dent, Genome Ctr, London, England.
[Verweij, Niek; van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
[Thorleifsson, Gudmar; Kong, Augustine; Stefansson, Kari] deCODE Genet, Rekjavik, Iceland.
[Hottenga, Jouke-Jan; Willemsen, Gonneke; de Geus, Eco J. C.; Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.
[Hottenga, Jouke-Jan; Willemsen, Gonneke; de Geus, Eco J. C.; Boomsma, Dorret I.] EMGO Inst, Amsterdam, Netherlands.
[Shah, Sonia] UCL, Univ Coll London Genet Inst UGI, London, England.
[Smith, Albert V.; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Smith, Albert V.; Gudnason, Vilmundur; Stefansson, Kari] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Gieger, Christian; Mueller-Nurasyid, Martina] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, Neuherberg, Germany.
[Salo, Perttu; Perola, Markus; Antti, Jula] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Perola, Markus; Kaprio, Jaakko; Ripatti, Samuli] Univ Helsinki, Inst Mol Med, Finland FIMM, Helsinki, Finland.
[Timpson, Nicholas J.; Evans, David M.; Smith, George Davey] Univ Bristol, Sch Social & Community Med, MRC Council Ctr Causal Anal Translat Epidemiol CA, Bristol, Avon, England.
[Wu, Ying; Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Andrews, Jeanette S.] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA.
[Hui, Jennie; James, Alan L.; Beilby, John P.] Sir Charles Gairdner Hosp, Busselton Populat Med Res Inst, Nedlands, WA 6009, Australia.
[Hui, Jennie] Univ Western Australia, Sch Populat Hlth, Nedlands, WA 6009, Australia.
[Hui, Jennie; Beilby, John P.] Univ Western Australia, Sch Pathol & Lab Med, Nedlands, WA 6009, Australia.
[Hui, Jennie; Beilby, John P.] PathW Lab Med WA, Nedlands, WA, Australia.
[Bielak, Lawrence F.; Zhao, Wei; Peyser, Patricia A.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Navarro, Pau; Vitart, Veronique; Hayward, Caroline; Campbell, Susan; Hastie, Nicholas D.; Wright, Alan F.] Univ Edinburgh, Western Gen Hosp, Med Res Council Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.
[Isaacs, Aaron; Rivadeneira, Fernando; Uitterlinden, Andre G.; Oostra, Ben A.; van Duijn, Cornelia M.] CMSB, Leiden, Netherlands.
[Isaacs, Aaron; Willems, Sara M.; Oostra, Ben A.; van Duijn, Cornelia M.] Erasmus Univ, Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands.
[Esko, Tonu; Mihailov, Evelin; Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia.
[Fraser, Ross M.; Bolton, Jennifer L.; Fowkes, Gerard R.; Wild, Sarah H.; Rudan, Igor; Campbell, Harry; Wilson, James F.; Price, Jackie F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
[Voight, Benjamin F.] Broad Inst Harvard & MIT, Boston, MA USA.
[Voight, Benjamin F.] Univ Penn, Perelman Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA.
[Raychaudhuri, Soumya] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA.
[Raychaudhuri, Soumya] Brigham & Womens Hosp, Div Rheumatol, Boston, MA 02115 USA.
[Chen, Han; Liu, Ching-Ti; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Rybin, Denis] Boston Univ, Data Coordinating Ctr, Boston, MA 02215 USA.
[Beckmann, Jacques S.] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland.
[Beckmann, Jacques S.] Univ Lausanne Hosp, CHUV, Serv Med Genet, Lausanne, Switzerland.
[Chines, Peter S.; Bonnycastle, Lori L.; Collins, Francis S.] NHGRI, Genome Technol Branch, US Natl Inst Hlth NIH, Bethesda, MD 20892 USA.
[Song, Kijoung; Waterworth, Dawn M.] GlaxoSmithKline, Genet, Upper Merion, PA USA.
[Tanaka, Toshiko; Ferrucci, Luigi] NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA.
[Goel, Anuj; Pramstaller, Peter P.; Watkins, Hugh; Farrall, Martin] Univ Oxford, Dept Cardiovasc Med, Oxford, England.
[Hicks, Andrew A.] Univ Lubeck, European Acad Bozen Bolzano EURAC, Ctr Biomed, Bolzano, Italy.
[An, Ping; Province, Michael A.; Borecki, Ingrid B.] Washington Univ, Sch Med, Div Stat Genom, St Louis, MO USA.
[Mueller-Nurasyid, Martina] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
[Mueller-Nurasyid, Martina] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany.
[Franco-Cereceda, Anders] Karolinska Inst, Dept Mol Med & Surg, Cardiothorac Surg Unit, Stockholm, Sweden.
[Marullo, Letizia] Univ Ferrara, Genet Sect, Dept Evolutionary Biol, I-44100 Ferrara, Italy.
[Jansen, Hanneke] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.
[Oldehinkel, Albertine J.] Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Pathol Emot, Groningen, Netherlands.
[Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA.
[North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Hallmans, Goeran] Umea Univ Hosp, Dept Publ Hlth & Clin Med, Sect Nutr Res, S-90185 Umea, Sweden.
[Oksa, Heikki; Saaristo, Timo E.] Pirkanmaa Hosp Dist, Tampere, Finland.
[Nagaraja, Ramaiah] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA.
[Bakker, Stephan J. L.] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Groningen, Netherlands.
[Kumari, Meena; Kivimaki, Mika; Hingorani, Aroon; Langenberg, Claudia] UCL, Dept Epidemiol & Publ Hlth, London, England.
[Gigante, Bruna; de Faire, Ulf] Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, Stockholm, Sweden.
[Herder, Christian] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, D-40225 Dusseldorf, Germany.
[Mangino, Massimo; Small, Kerrin; Spector, Tim D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England.
[Miljkovic, Iva] Univ Pittsburgh, Ctr Aging & Populat Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Liu, Yongmei] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC USA.
[Atalay, Mustafa; Lakka, Timo A.] Univ Eastern Finland, Inst Biomed, Kuopio, Finland.
[Kiess, Wieland; Stumvoll, Michael; Toenjes, Anke; Koerner, Antje] Univ Leipzig, Integrated Res & Treatment Ctr IFB Adipos Dis, Leipzig, Germany.
[Kiess, Wieland; Koerner, Antje] Univ Leipzig, Dept Womens & Child Hlth, Pediat Res Ctr, Leipzig, Germany.
[James, Alan L.] Univ Western Australia, Sch Med & Pharmacol, Nedlands, WA 6009, Australia.
[Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands.
[Rivadeneira, Fernando; Uitterlinden, Andre G.; Oostra, Ben A.; van Duijn, Cornelia M.] Genom Initiat NGI, Netherlands Consortium Hlth Ageing NCHAH, Leiden, Netherlands.
[Rivadeneira, Fernando; Uitterlinden, Andre G.; Hofman, Albert; van Duijn, Cornelia M.] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
[Palmer, Colin N. A.; Doney, Alex S. F.; Morris, Andrew D.] Univ Dundee, Med Res Inst, Dundee, Scotland.
[Smit, Johannes H.; Penninx, Brenda W.] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Amsterdam, Netherlands.
[Polasek, Ozren; Zemunik, Tatijana] Univ Split, Fac Med, Split, Croatia.
[Hercberg, Serge] Univ Paris 13, INRA, INSERM, U557,U1125, Bobigny, France.
[Dimitriou, Maria; Dedoussis, George V.] Harokopio Univ, Dept Nutr & Dietet, Athens, Greece.
[Kovacs, Peter] Univ Leipzig, Interdisciplinary Ctr Clin Res, Leipzig, Germany.
[Lindstrom, Jaana; Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland.
[Bandinelli, Stefania] Azienda Sanit Firenze, Dept Geriatr, Florence, Italy.
[Basart, Hanneke V.; Hovingh, G. Kees] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands.
[Rathmann, Wolfgang] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Biometr & Epidemiol, D-40225 Dusseldorf, Germany.
[Grallert, Harald; Illig, Thomas] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany.
[Maerz, Winfried] Synlab Acad, Mannheim, Germany.
[Maerz, Winfried; Kleber, Marcus E.] Heidelberg Univ, Med Fac Mannheim, Mannheim Inst Publ Hlth Social & Prevent Med, D-6800 Mannheim, Germany.
[Kleber, Marcus E.] Ludwigshafen Risk & Cardiovasc Hlth LURIC Study, Freiburg, Germany.
[Boehm, Bernhard O.] Univ Hosp, Dept Med, Div Endocrinol & Diabet, Ulm, Germany.
[Peters, Annette] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany.
[Pramstaller, Peter P.] Gen Cent Hosp, Dept Neurol, Bolzano, Italy.
[Pramstaller, Peter P.; Toenjes, Anke] Univ Lubeck, Dept Neurol, Lubeck, Germany.
[Stumvoll, Michael] Univ Leipzig, Dept Med, Leipzig, Germany.
[Bergman, Richard N.] Cedars Sinai Med Ctr, Diabet & Obes Res Inst, Los Angeles, CA 90048 USA.
[Tuomilehto, Jaakko] S Ostrobothnia Cent Hosp, Seinajoki, Finland.
[Tuomilehto, Jaakko] Hosp Univ La Paz, Red RECAVA La Red Temat Invest Cooperat Enfermeda, Madrid, Spain.
[Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria.
[Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA.
[Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Vollenweider, Peter] Univ Lausanne Hosp, Dept Internal Med, Lausanne, Switzerland.
[Uusitupa, Matti] Univ Eastern Finland, Dept Publ Hlth & Clin Nutr, Kuopio, Finland.
[Uusitupa, Matti] Kuopio Univ Hosp, Res Unit, SF-70210 Kuopio, Finland.
[Kyvik, Kirsten O.] Odense Patient Data Explorat Network OPEN, Odense, Denmark.
[Kyvik, Kirsten O.] Inst Reg Hlth Serv Res, Odense, Denmark.
[Kaprio, Jaakko] Univ Helsinki, Dept Publ Hlth, Hjelt Inst, Helsinki, Finland.
[Kaprio, Jaakko] Natl Inst Hlth & Welf, Dept Mental Hlth & Subst Abuse Serv, Helsinki, Finland.
[Meneton, Pierre] Ctr Rech Cordeliers, INSTERM U872, Paris, France.
[Lind, Lars] Uppsala Univ, Dept Med Sci, Uppsala, Sweden.
[Shuldiner, Alan R.] Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Baltimore, MD 21218 USA.
[Kuusisto, Johanna; Laakso, Markku] Univ Eastern Finland, Dept Med, Kuopio, Finland.
[Bornstein, Stefan R.; Schwarz, Peter E. H.] Univ Dresden, Med Fac Carl Gustav Carus, Dept Med 3, Dresden, Germany.
[Lakka, Timo A.; Rauramaa, Rainer] Kuopio Res Inst Exercise Med, Kuopio, Finland.
[Rauramaa, Rainer] Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, SF-70210 Kuopio, Finland.
[Adair, Linda S.] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA.
[Illig, Thomas] Hannover Med Sch, Hannover Unified Biobank, D-3000 Hannover, Germany.
[Hamsten, Anders] Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden.
[Keinanen-Kiukaanniemi, Sirkka M.] Univ Oulu, Inst Hlth Sci, Fac Med, Oulu, Finland.
[Keinanen-Kiukaanniemi, Sirkka M.] Oulu Univ Hosp, Unit Gen Practice, Oulu, Finland.
[Saaristo, Timo E.] Finnish Diabet Assoc, Tampere, Finland.
[Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Sattar, Naveed] Univ Glasgow, Inst Cardiovasc & Med Sci, British Heart Fdn BHF Bldg, Glasgow, Lanark, Scotland.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA.
[Ripatti, Samuli] Natl Inst Hlth & Welf, Publ Hlth Genom Unit, Helsinki, Finland.
[Ripatti, Samuli] Wellcome Trust Sanger Inst, Hinxton, England.
[Salomaa, Veikko] Natl Inst Hlth & Welf, Unit Chron Dis Epidemiol & Prevent, Helsinki, Finland.
[Balkau, Beverley] INSERM, Ctr Rech Epidemiol & Sante Populat CESP, Ctr Res Epidemiol & Publ Hlth, Epidemiol Diabet Obes & Chron Kidney Dis Lifecour, Villejuif, France.
[Balkau, Beverley] Univ Paris 11, UMRS 1018, Villejuif, France.
[Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Sch Publ Hlth, Dept Genom Common Dis, London, England.
[Pouta, Anneli] Univ Oulu, Dept Clin Sci Obstet & Gynecol, Oulu, Finland.
[Pouta, Anneli; Jarvelin, Marjo-Riitta] Natl Inst Hlth & Welf, Dept Lifecourse & Serv, Oulu, Finland.
[Jarvelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, Oulu, Finland.
[Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Fac Med, MRC Hlth Protect Agcy HPA,Ctr Environm & Hlth, Dept Epidemiol & Biostat,Sch Publ Hlth, London, England.
[Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland.
[Bouatia-Naji, Nabila] INSERM, U970, Paris Cardiovasc Res Ctr PARCC, Paris, France.
[McCarthy, Mark I.] Churchill Hosp, Oxford Natl Inst Hlth Res NIHR, Biomed Res Ctr, Oxford OX3 7LJ, England.
[Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA.
[Florez, Jose C.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
[Barroso, Ines] Addenbrookes Hosp, Inst Metab Sci, NIHR Cambridge Biomed Res Ctr, Cambridge, England.
[Barroso, Ines] Univ Cambridge, Addenbrookes Hosp, Metab Res Labs, Inst Metab Sci, Cambridge CB2 2QQ, England.
RP Florez, JC (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
EM jcflorez@partners.org; claudia.langenberg@mrc-epid.cam.ac.uk;
erik.ingelsson@ki.se; inga@well.ox.ac.uk; ib1@sanger.ac.uk
RI Smith, Albert/K-5150-2015; Kyvik, Kirsten /K-5680-2016; Study,
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Caroline/M-8818-2016; BOUATIA-NAJI, NABILA/D-5863-2013; Schwarz,
Peter/B-5127-2013; Fox, Laura /C-6249-2016; Verweij, Niek/A-4499-2017;
Davey Smith, George/A-7407-2013; Magnusson, Patrik/C-4458-2017; Yengo,
Loic/D-2692-2017; Hicks, Andrew/E-9518-2017; Johnson, Paul/O-9695-2014;
Korner, Antje/B-3988-2015; Boehm, Bernhard/F-8750-2015; Bakker,
Stephan/J-4023-2015; Gudnason, Vilmundur/K-6885-2015; Ripatti,
Samuli/H-9446-2014; Wilson, James F/A-5704-2009; Polasek,
Ozren/B-6002-2011; de Geus, Eco/M-9318-2015; Rivadeneira,
Fernando/O-5385-2015; Prokopenko, Inga/H-3241-2014; Peters,
Annette/A-6117-2011; Fraser, Ross/J-9519-2012; Deloukas,
Panos/B-2922-2013; Grallert, Harald/B-3424-2013; Beckmann, Jacques S
/A-9772-2008; Evans, David/H-6325-2013; Colaus, PsyColaus/K-6607-2013;
Lagou, Vasiliki/N-8451-2013; Pramstaller, Peter/C-2357-2008;
Strawbridge, Rona/H-5422-2012; Fall, Tove/O-7226-2014; Rudan,
Igor/I-1467-2012; Gigante, Bruna/I-9252-2012; Palmer, Colin/C-7053-2008;
OI Verweij, Niek/0000-0002-4303-7685; Forouhi, Nita/0000-0002-5041-248X;
Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Chen,
Han/0000-0002-9510-4923; Navarro, Pau/0000-0001-5576-8584; Watkins,
Hugh/0000-0002-5287-9016; Small, Kerrin/0000-0003-4566-0005; Varga,
Tibor/0000-0002-2383-699X; Evans, David/0000-0003-0663-4621; Kaprio,
Jaakko/0000-0002-3716-2455; Timpson, Nicholas/0000-0002-7141-9189;
Lakka, Timo/0000-0002-9199-2871; Dupuis, Josee/0000-0003-2871-3603;
Folkersen, Lasse/0000-0003-0708-9530; Gieger,
Christian/0000-0001-6986-9554; Franks, Paul/0000-0002-0520-7604; St
Pourcain, Beate/0000-0002-4680-3517; Kumari, Meena/0000-0001-9716-1035;
Miljkovic, Iva/0000-0002-3155-9777; Rybin, Denis/0000-0002-3657-4829;
sanna, serena/0000-0002-3768-1749; Kivimaki, Mika/0000-0002-4699-5627;
Monsalve, Beatriz Elena/0000-0002-5994-866X; Esko,
Tonu/0000-0003-1982-6569; Shungin, Dmitry/0000-0001-7900-5856; Mulas,
Antonella/0000-0002-6856-1483; Bouatia-Naji, Nabila/0000-0001-5424-2134;
Johnson, Toby/0000-0002-5998-3270; Sidore, Carlo/0000-0001-7504-7477;
Magi, Reedik/0000-0002-2964-6011; Smith, Albert/0000-0003-1942-5845;
Kyvik, Kirsten /0000-0003-2981-0245; mangino,
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Schwarz, Peter/0000-0001-6317-7880; Davey Smith,
George/0000-0002-1407-8314; Yengo, Loic/0000-0002-4272-9305; Hicks,
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Eleanor/0000-0002-8616-6444; Kleber, Marcus/0000-0003-0663-7275
FU National Institutes of Health [N01-AG-1-2100]; National Institute on
Aging Intramural Research Program; Hjartavernd (the Icelandic Heart
Association); Althingi (the Icelandic Parliament)
FX The AGES-Reykjavik study was supported by a contract from the National
Institutes of Health (N01-AG-1-2100), National Institute on Aging
Intramural Research Program, Hjartavernd (the Icelandic Heart
Association) and the Althingi (the Icelandic Parliament).
NR 98
TC 248
Z9 253
U1 4
U2 69
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
EI 1546-1718
J9 NAT GENET
JI Nature Genet.
PD SEP
PY 2012
VL 44
IS 9
BP 991
EP +
DI 10.1038/ng.2385
PG 18
WC Genetics & Heredity
SC Genetics & Heredity
GA 001WP
UT WOS:000308491200010
PM 22885924
ER
PT J
AU Holt, KE
Baker, S
Weill, FX
Holmes, EC
Kitchen, A
Yu, J
Sangal, V
Brown, DJ
Coia, JE
Kim, DW
Choi, SY
Kim, SH
da Silveira, WD
Pickard, DJ
Farrar, JJ
Parkhill, J
Dougan, G
Thomson, NR
AF Holt, Kathryn E.
Baker, Stephen
Weill, Francois-Xavier
Holmes, Edward C.
Kitchen, Andrew
Yu, Jun
Sangal, Vartul
Brown, Derek J.
Coia, John E.
Kim, Dong Wook
Choi, Seon Young
Kim, Su Hee
da Silveira, Wanderley D.
Pickard, Derek J.
Farrar, Jeremy J.
Parkhill, Julian
Dougan, Gordon
Thomson, Nicholas R.
TI Shigella sonnei genome sequencing and phylogenetic analysis indicate
recent global dissemination from Europe
SO NATURE GENETICS
LA English
DT Article
ID FREE-LIVING AMEBAS; ESCHERICHIA-COLI; PLESIOMONAS-SHIGELLOIDES;
VIETNAMESE CHILDREN; BACILLARY DYSENTERY; TRANSMISSION; EVOLUTION;
PLASMID; DIVERSITY; PATTERNS
AB Shigella are human-adapted Escherichia coli that have gained the ability to invade the human gut mucosa and cause dysentery(1,2), spreading efficiently via low-dose fecal-oral transmission(3,4). Historically, S. sonnei has been predominantly responsible for dysentery in developed countries but is now emerging as a problem in the developing world, seeming to replace the more diverse Shigella flexneri in areas undergoing economic development and improvements in water quality(4-6). Classical approaches have shown that S. sonnei is genetically conserved and clonal(7). We report here whole-genome sequencing of 132 globally distributed isolates. Our phylogenetic analysis shows that the current S. sonnei population descends from a common ancestor that existed less than 500 years ago and that diversified into several distinct lineages with unique characteristics. Our analysis suggests that the majority of this diversification occurred in Europe and was followed by more recent establishment of local pathogen populations on other continents, predominantly due to the pandemic spread of a single, rapidly evolving, multidrug-resistant lineage.
C1 [Holt, Kathryn E.] Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic, Australia.
[Baker, Stephen; Farrar, Jeremy J.] Univ Oxford, Clin Res Unit, Wellcome Trust Major Overseas Programme, Hosp Trop Dis, Ho Chi Minh City, Vietnam.
[Weill, Francois-Xavier] Inst Pasteur, Unite Bacteries Pathogenes Enter, Paris, France.
[Holmes, Edward C.; Kitchen, Andrew] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Holmes, Edward C.] US Natl Inst Hlth, Fogarty Int Ctr, Bethesda, MD USA.
[Yu, Jun; Sangal, Vartul] Univ Strathclyde, Strathclyde Inst Pharm & Biomed Sci, Glasgow, Lanark, Scotland.
[Brown, Derek J.; Coia, John E.] Stobhill Hosp, Scottish Salmonella Shigella & Clostridium Diffic, Glasgow, Lanark, Scotland.
[Kim, Dong Wook; Choi, Seon Young; Kim, Su Hee] IVI, Mol Biol Lab, Seoul, South Korea.
[Kim, Dong Wook] Hanyang Univ Ansan, Coll Pharm, Dept Pharm, Kyeonggi Do, South Korea.
[da Silveira, Wanderley D.] Univ Estadual Campinas, UNICAMP, Inst Biol, Dept Genet Evolut & Bioagents, Campinas, SP, Brazil.
[Pickard, Derek J.; Parkhill, Julian; Dougan, Gordon; Thomson, Nicholas R.] Wellcome Trust Sanger Inst, Cambridge, England.
RP Holt, KE (reprint author), Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic, Australia.
EM kholt@unimelb.edu.au; nrt@sanger.ac.uk
RI Parkhill, Julian/G-4703-2011; Holt, Kathryn/A-8108-2012; Kim, Dong
Wook/H-8253-2015; Dias da Silveira, Wanderley/C-6420-2012
OI Parkhill, Julian/0000-0002-7069-5958; Holt, Kathryn/0000-0003-3949-2471;
Kim, Dong Wook/0000-0001-5351-7597; Sangal, Vartul/0000-0002-7405-8446;
Weill, Francois-Xavier/0000-0001-9941-5799; Farrar,
Jeremy/0000-0002-2700-623X; Holmes, Edward/0000-0001-9596-3552;
FU Wellcome Trust [0689]; Victorian Life Sciences Computation Initiative
(VLSCI) [VR0082]; National Health & Medical Research Council (NHMRC) of
Australia [628930]; Oak Foundation Fellowship through Oxford University
[OAKF9]; Li Ka Shing foundation [LG13]; Institut de Veille Sanitaire; UK
Medical Research Council (MRC) [G0800173]; Korean Ministry of Knowledge
and Economy (MKE) [RTI05-01-01]
FX We thank M. Levine (University of Maryland School of Medicine) and C.
Tang (University of Oxford) for their kind gift of S. sonnei strain 53G.
This work was supported by the Wellcome Trust (0689) and a Victorian
Life Sciences Computation Initiative (VLSCI) grant (VR0082) on its Peak
Computing Facility at the University of Melbourne (an initiative of the
Victorian Government, Australia). K.E.H. was supported by a Fellowship
from the National Health & Medical Research Council (NHMRC) of Australia
(628930); S.B. is supported by an Oak Foundation Fellowship through
Oxford University (OAKF9) and by the Li Ka Shing foundation (LG13);
F.X.W. was partially funded by the Institut de Veille Sanitaire; J.Y.
was supported by a UK Medical Research Council (MRC) grant (G0800173);
and D.W.K. was partially supported by grant RTI05-01-01 from the Korean
Ministry of Knowledge and Economy (MKE).
NR 40
TC 82
Z9 84
U1 2
U2 26
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
EI 1546-1718
J9 NAT GENET
JI Nature Genet.
PD SEP
PY 2012
VL 44
IS 9
BP 1056
EP +
DI 10.1038/ng.2369
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA 001WP
UT WOS:000308491200020
PM 22863732
ER
PT J
AU Fleming, GM
Walters, S
Goldstein, SL
Alexander, SR
Baum, MA
Blowey, DL
Bunchman, TE
Chua, AN
Fletcher, SA
Flores, FX
Fortenberry, JD
Hackbarth, R
McBryde, K
Somers, MJG
Symons, JM
Brophy, PD
AF Fleming, Geoffrey M.
Walters, Scott
Goldstein, Stuart L.
Alexander, Steven R.
Baum, Michelle A.
Blowey, Douglas L.
Bunchman, Timothy E.
Chua, Annabelle N.
Fletcher, Sarah A.
Flores, Francisco X.
Fortenberry, James D.
Hackbarth, Richard
McBryde, Kevin
Somers, Michael J. G.
Symons, Jordan M.
Brophy, Patrick D.
TI Nonrenal indications for continuous renal replacement therapy: A report
from the Prospective Pediatric Continuous Renal Replacement Therapy
Registry Group
SO PEDIATRIC CRITICAL CARE MEDICINE
LA English
DT Article
DE continuous renal replacement therapy; detoxification; inborn error of
metabolism; intermittent hemodialysis; tumor lysis syndrome
ID CONTINUOUS VENOVENOUS HEMOFILTRATION; TUMOR LYSIS SYNDROME;
INBORN-ERRORS; PERITONEAL-DIALYSIS; ACUTE MANAGEMENT; PPCRRT REGISTRY;
HYPER-AMMONEMIA; METABOLISM; HEMODIALYSIS; CHILDREN
AB Objective: Continuous renal replacement therapy is the most often implemented dialysis modality in the pediatric intensive care unit setting for patients with acute kidney injury. However, it also has a role in the management of patients with nonrenal indications such as clearance of drugs and intermediates of disordered cellular metabolism.
Measurements and Methods: Using data from the multicenter Prospective Pediatric Continuous Renal Replacement Therapy Registry, we report a cohort of pediatric patients receiving continuous renal replacement therapy for nonrenal indications. Nonrenal indications were obtained from the combination of "other" category for continuous renal replacement therapy initiation and patient diagnosis (both primary and secondary). This cohort was further divided into three subgroups: inborn errors of metabolism, drug toxicity, and tumor lysis syndrome.
Results: From 2000 to 2005, a total of 50 continuous renal replacement therapy events with nonrenal indications for therapy were included in the Prospective Pediatric Continuous Renal Replacement Therapy Registry. Indication-specific survival of the subgroups was 62% (inborn errors of metabolism), 82% (tumor lysis syndrome), and 95% (drug toxicity). The median small solute dose delivered among the subgroups ranged from 2125 to 8213 mL/1.73 m(2)/hr, with 54%-59% receiving solely diffusion-based clearance as continuous venovenous hemodialysis. No association was established between survival and dose delivered, modality of continuous renal replacement therapy, or use of intermittent hemodialysis prior to continuous renal replacement therapy.
Conclusions: Pediatric patients requiring continuous renal replacement therapy for nonrenal indications are a distinct cohort within the population receiving renal replacement therapy with little published experience of outcomes for this group. Survival within this cohort varies by indication for continuous renal replacement therapy and is not associated with continuous renal replacement therapy modality. Additionally, survival is not associated with small solute doses delivered within a cohort receiving >2000 mL/1.73 m(2)/hr. Our data suggest metabolic control is established rapidly in pediatric patients and that acute detoxification may be provided with continuous renal replacement therapy for both the initial and maintenance phases of treatment using either convection or diffusion at appropriate doses. (Pediatr Crit Care Med 2012; 13:e299-e304)
C1 [Fleming, Geoffrey M.] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA.
[Walters, Scott] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA.
[Goldstein, Stuart L.] Cincinnati Childrens Hosp, Ctr Acute Care Nephrol, Cincinnati, OH USA.
Lucille Packard Childrens Hosp, Palo Alto, CA USA.
[Alexander, Steven R.] Stanford Sch Med, Dept Pediat, Palo Alto, CA USA.
[Baum, Michelle A.; Somers, Michael J. G.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
Childrens Hosp, Boston, MA 02115 USA.
[Blowey, Douglas L.] Childrens Mercy Hosp, Dept Pediat, Kansas City, MO 64108 USA.
Univ Missouri, Kansas City, MO 64110 USA.
[Bunchman, Timothy E.] Virginia Commonwealth Univ, Dept Pediat, Sch Med, Richmond, VA USA.
[Chua, Annabelle N.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
[Fletcher, Sarah A.] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37212 USA.
[Flores, Francisco X.] Univ S Florida, All Childrens Hosp, Dept Pediat, Coll Med, St Petersburg, FL 33701 USA.
Childrens Healthcare Atlanta Egleston, Atlanta, GA USA.
[Fortenberry, James D.] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA.
[Hackbarth, Richard] Michigan State Univ, Dept Pediat, Grand Rapids, MI USA.
Helen DeVos Childrens Hosp, Grand Rapids, MI USA.
[McBryde, Kevin] NIDDK, NIH, Bethesda, MD USA.
[Symons, Jordan M.] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA.
Seattle Childrens Hosp, Seattle, WA USA.
[Brophy, Patrick D.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA.
RP Fleming, GM (reprint author), Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA.
EM Geoffrey.fleming@vanderbilt.edu
FU Gambro Renal Products; Baxter Healthcare; Dialysis Solutions
Incorporated; Katherine Dodd Faculty Scholars Program; Department of
Pediatrics; Vanderbilt University School of Medicine
FX The ppCRRT Registry was supported by unrestricted grant funding from
Gambro Renal Products, Baxter Healthcare, Dialysis Solutions
Incorporated, and B. Braun. Statistical analysis was supported by the
Katherine Dodd Faculty Scholars Program, Department of Pediatrics,
Vanderbilt University School of Medicine.
NR 30
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Z9 8
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1529-7535
J9 PEDIATR CRIT CARE ME
JI Pediatr. Crit. Care Med.
PD SEP
PY 2012
VL 13
IS 5
BP E299
EP E304
DI 10.1097/PCC.0b013e31824fbd76
PG 6
WC Critical Care Medicine; Pediatrics
SC General & Internal Medicine; Pediatrics
GA 002NB
UT WOS:000308537800005
PM 22805158
ER
PT J
AU Harbell, J
Fung, J
Nissen, N
Olthoff, K
Florman, SS
Hanto, DW
Light, J
Bartlett, ST
Tzakis, AG
Pearson, TC
Barin, B
Roland, ME
Stock, PG
AF Harbell, Jack
Fung, John
Nissen, Nicholas
Olthoff, Kim
Florman, Sander S.
Hanto, Douglas W.
Light, Jimmy
Bartlett, Steve T.
Tzakis, Andreas G.
Pearson, Thomas C.
Barin, Burc
Roland, Michelle E.
Stock, Peter G.
CA HIV-TR Investigators
TI Surgical complications in 275 HIV-infected liver and/or kidney
transplantation recipients
SO SURGERY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; RENAL-TRANSPLANTATION; UROLOGICAL
COMPLICATIONS; VASCULAR COMPLICATIONS; BILIARY COMPLICATIONS; OUTCOMES;
IMMUNOSUPPRESSION; RISK
AB Background. In this report, we examine the surgical safety and complications (SC) among 125 liver (L) and 150 kidney (K) HIV+ transplantation (TX) recipients in a prospective nonrandomized U.S. multicenter trial.
Methods. Subjects were required to have CD4(+) Toll counts >200/100 cells/mm(3) (K/L) and undetectable plasma HIV-1 RNA (Viral Load [VL]) (K) or expected posttransplantation suppression (L). Impact of SCs (N >= 7) was evaluated by use of the proportional hazards models. Baseline morbidity predictors for SCs (N >= 7) were assessed in univariate proportional hazards models.
Results. At median 2.7 (interquartile range 1.9-4.1) and 2.3 (1.0-3.7) years after TX, 3-month and 1-year graft survival were [K] 96% (95% CI 91%-98%) and 91% (95% CI 85%-94%) and [L] 91% (95% CI 85%-95%) and 77% (95% CI 69%-84%), respectively. A total of 14 K and 28 L graft losses occurred in the first year; 6K and 11 L were in the first 3 months. A total of 26 (17%) K and 43 (34%) L experienced 29 and 62 SCs, respectively. In the liver multivariate model, re-exploration was marginally associated (hazard ratio [HR] 2.8; 95% CI 1.0-8.4; P = .06) with increased risk of graft loss, whereas a greater MELD score before transplantation (HR 1.07 per point increase; 95% CI: 1.01-1.14; P = .02), and detectable viral load before TX (HR 3.6; 95% CI 0.9-14.6; P = .07) was associated with an increased risk of wound infections/dehiscence.
Conclusion. The rates and outcomes of surgical complications are similar to what has been observed in the non-HIV setting in carefully selected HIV-infected liver and kidney TX recipients. (Surgery 2012;152:376-81.)
C1 [Harbell, Jack; Roland, Michelle E.; Stock, Peter G.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Nissen, Nicholas] Cedars Sinai, Los Angeles, CA USA.
[Fung, John] Cleveland Clin, Cleveland, OH 44106 USA.
[Olthoff, Kim] Univ Penn, Philadelphia, PA 19104 USA.
[Florman, Sander S.] Mt Sinai Med Ctr, New York, NY 10029 USA.
[Hanto, Douglas W.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Light, Jimmy] Washington Hosp Ctr, Washington, DC 20010 USA.
[Bartlett, Steve T.] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA.
[Tzakis, Andreas G.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Pearson, Thomas C.] Emory Univ, Sch Med, Atlanta, GA USA.
[Barin, Burc] EMMES Corp, Rockville, MD USA.
[HIV-TR Investigators] NIH, Solid Organ Transplantat HIV Multisite Study, Bethesda, MD 20892 USA.
RP Harbell, J (reprint author), Univ Calif San Francisco, 513 Parnassus Ave,Room S321, San Francisco, CA 94143 USA.
EM jack.harbell@ucsfmedctr.org
FU Solid Organ Transplantation in HIV: Multi-Site Study [AI052748];
National Institute of Allergy and infectious Diseases
FX Supported by the Solid Organ Transplantation in HIV: Multi-Site Study
(AI052748) funded by the National Institute of Allergy and infectious
Diseases. The content is solely the responsibility of the authors and
does not necessarily represent the official views of the National
Institute of Allergy And Infectious Diseases or the National Institutes
of Health.
NR 25
TC 7
Z9 7
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0039-6060
J9 SURGERY
JI Surgery
PD SEP
PY 2012
VL 152
IS 3
BP 376
EP 381
DI 10.1016/j.surg.2012.06.012
PG 6
WC Surgery
SC Surgery
GA 003PJ
UT WOS:000308623500011
PM 22938898
ER
PT J
AU Harrington, JM
Boyd, WA
Smith, MV
Rice, JR
Freedman, JH
Crumbliss, AL
AF Harrington, James M.
Boyd, Windy A.
Smith, Marjolein V.
Rice, Julie R.
Freedman, Jonathan H.
Crumbliss, Alvin L.
TI Amelioration of Metal-Induced Toxicity in Caenorhabditis elegans:
Utility of Chelating Agents in the Bioremediation of Metals
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE C; elegans; cadmium; copper; zinc; nickel; chelator; remediation
ID C. ELEGANS; NEMATODE; BIOAVAILABILITY; MODEL; SALTS; ACID
AB The presence of toxic amounts of transition metals in the environment may originate from a range of human activities and natural processes. One method for the removal of toxic levels of metals is through chelation by small molecules. However, chelation is not synonymous with detoxification and may not affect the bioavailability of the metal. To test the bioavailability of chelated metals in vivo, the effects of several metal/chelator combinations were tested in the environmentally relevant organism Caenorhabditis elegans. The effect of metal exposure on nematode growth was used to determine the toxicity of cadmium, copper, nickel, and zinc. The restoration of growth to levels observed in nonexposed nematodes was used to determine the protective effects of the polydentate chelators: acetohydroxamic acid (AHA), cyclam, cysteine, calcium EDTA, desferrioxamine B, 1,2-dimethyl,3-hydroxy,4-pyridinone, and histidine. Cadmium toxicity was removed only by EDTA; copper toxicity was removed by all of the chelators except AHA; nickel toxicity was removed by cyclam, EDTA, and histidine; and zinc toxicity was removed by only EDTA. These results demonstrate the utility of polydentate chelators in the remediation of metal-contaminated systems. They also demonstrate that although the application of a chelator to metal contaminants may be effective, binding alone cannot be used to predict the level of remediation. Remediation depends on a number of factors, including metal complex speciation in the environment.
C1 [Harrington, James M.; Crumbliss, Alvin L.] Duke Univ, Dept Chem, Durham, NC 27708 USA.
[Boyd, Windy A.; Rice, Julie R.; Freedman, Jonathan H.] Natl Toxicol Program, Biomol Screening Branch, Res Triangle Pk, NC 27709 USA.
[Smith, Marjolein V.] SRA Int Inc, Durham, NC 27713 USA.
[Rice, Julie R.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
RP Freedman, JH (reprint author), NIEHS, Mol Toxicol Lab, Mail Drop E1-05,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM freedma1@niehs.nih.gov
OI Boyd, Windy/0000-0003-3803-3716
FU National Science Foundation [CHE CHE0809466]; NIH National Center for
Research Resources; NIH, NIEHS; NTP [Z01ES102045, Z01ES102046]; NIEHS
[HHSN273201000086U]; Duke University Center for Biomolecular and Tissue
Engineering
FX A.L.C. thanks the National Science Foundation (CHE CHE0809466) for
partial financial support. Nematode strains used in this work were
provided by the Caenorhabditis Genetics Center, which is funded by the
NIH National Center for Research Resources. This work was supported (in
part) by the Intramural Research Program of the NIH, NIEHS, and the NTP
(Z01ES102045, Z01ES102046). Work by M.V.S. was supported by NIEHS
contract HHSN273201000086U. A.L.C. and J.M.H. thank the Duke University
Center for Biomolecular and Tissue Engineering for partial financial
support.
NR 40
TC 3
Z9 3
U1 4
U2 31
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
EI 1096-0929
J9 TOXICOL SCI
JI Toxicol. Sci.
PD SEP
PY 2012
VL 129
IS 1
BP 49
EP 56
DI 10.1093/toxsci/kfs191
PG 8
WC Toxicology
SC Toxicology
GA 998JN
UT WOS:000308234000006
PM 22641620
ER
PT J
AU Yucesoy, B
Johnson, VJ
Lummus, ZL
Kissling, GE
Fluharty, K
Gautrin, D
Malo, JL
Cartier, A
Boulet, LP
Sastre, J
Quirce, S
Germolec, DR
Tarlo, SM
Cruz, MJ
Munoz, X
Luster, MI
Bernstein, DI
AF Yucesoy, Berran
Johnson, Victor J.
Lummus, Zana L.
Kissling, Grace E.
Fluharty, Kara
Gautrin, Denyse
Malo, Jean-Luc
Cartier, Andre
Boulet, Louis-Philippe
Sastre, Joaquin
Quirce, Santiago
Germolec, Dori R.
Tarlo, Susan M.
Cruz, Maria-Jesus
Munoz, Xavier
Luster, Michael I.
Bernstein, David I.
TI Genetic Variants in Antioxidant Genes Are Associated With
Diisocyanate-Induced Asthma
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE diisocyanates; occupational asthma; antioxidant; genetics;
single-nucleotide polymorphism
ID GLUTATHIONE-S-TRANSFERASE; MANGANESE SUPEROXIDE-DISMUTASE; MICROSOMAL
EPOXIDE HYDROLASE; OBSTRUCTIVE PULMONARY-DISEASE; OCCUPATIONAL ASTHMA;
CHILDHOOD ASTHMA; BRONCHIAL-ASTHMA; TOLUENE DIISOCYANATE; AIR-POLLUTION;
LUNG-FUNCTION
AB Diisocyanates are a common cause of occupational asthma, but risk factors are not well defined. A case-control study was conducted to investigate whether genetic variants of antioxidant defense genes, glutathione S-transferases (GSTM1, GSTT1, GSTM3, GSTP1), manganese superoxide dismutase (SOD2), and microsomal epoxide hydrolase (EPHX1) are associated with increased susceptibility to diisocyanate-induced asthma (DA). The main study population consisted of 353 Caucasian French-Canadians from among a larger sample of 410 diisocyanate-exposed workers in three groups: workers with specific inhalation challenge (SIC) confirmed DA (DA(+), n = 95); symptomatic diisocyanate workers with a negative SIC (DA, n = 116); and asymptomatic exposed workers (AW, n = 142). Genotyping was performed on genomic DNA, using a 5-nuclease PCR assay. The SOD2 rs4880, GSTP1 rs1695, and EPHX1 rs2740171 variants were significantly associated with DA in both univariate and multivariate analyses. In the first logistic regression model comparing DA(+) and DA groups, SOD2 rs4880, GSTM1 (null), GSTP1 rs762803, and EPHX1 rs2854450 variants were associated with DA (p = 0.004, p = 0.047, p = 0.021, p < 0.001, respectively). Genotype combinations GSTT1*GSTP1 rs762803, GSTM1*EPHX1 rs2854450, EPHX1 rs2740168*EPHX1 rs1051741, and GSTP1 rs762803*EPHX1 rs2740168 were also associated with DA in this model (p = 0.027, p = 0.002, p = 0.045, p = 0.044, respectively). The GSTP1 rs1695 and EPHX1 rs1051741 and rs2740171 variants showed an association with DA in the second model comparing DA(+) and AW groups (p = 0.040, p = 0.019, p = 0.002, respectively). The GSTM3 rs110913*EPHX1 rs1051741 genotype combination was also associated with DA under this model (p = 0.042). The results suggest that variations in SOD2, GST, and EPHX1 genes and their interactions contribute to DA susceptibility.
C1 [Yucesoy, Berran] NIOSH, Hlth Effects Lab Div, Toxicol & Mol Biol Branch, CDC, Morgantown, WV 26505 USA.
[Johnson, Victor J.] BRT, Morrisville, NC USA.
[Lummus, Zana L.; Bernstein, David I.] Univ Cincinnati, Coll Med, Div Immunol Allergy & Rheumatol, Cincinnati, OH USA.
[Kissling, Grace E.; Germolec, Dori R.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
[Gautrin, Denyse; Malo, Jean-Luc; Cartier, Andre] Univ Montreal, Hop Sacre Coeur Montreal, Montreal, PQ, Canada.
[Boulet, Louis-Philippe] Univ Laval, Hop Laval, Ste Foy, PQ G1K 7P4, Canada.
[Sastre, Joaquin] Fdn Jimenez Diaz, Dept Allergy, Madrid, Spain.
[Sastre, Joaquin; Quirce, Santiago; Cruz, Maria-Jesus; Munoz, Xavier] CIBER Enfermedades Resp CIBERES, Madrid, Spain.
[Quirce, Santiago] Hosp La Paz IdiPAZ, Dept Allergy, Madrid, Spain.
[Tarlo, Susan M.] Univ Toronto, Toronto, ON, Canada.
[Cruz, Maria-Jesus; Munoz, Xavier] Hosp Valle De Hebron, Barcelona, Spain.
RP Yucesoy, B (reprint author), NIOSH, Hlth Effects Lab Div, Toxicol & Mol Biol Branch, CDC, 1095 Willowdale Rd,M-S 3014, Morgantown, WV 26505 USA.
EM byucesoy@cdc.gov
RI Munoz, Xavier/I-9009-2014; Cruz, Maria Jesus/I-9073-2014
OI Cruz, Maria Jesus/0000-0001-9759-5466
FU National Institute of Environmental Health - Sciences [Y1-ES0001];
National Institute for Occupational Safety and Health [Y1-ES0001];
NIOSH/CDC [R01 OH 008795]
FX This work was supported in part by an interagency agreement between
National Institute of Environmental Health - Sciences and National
Institute for Occupational Safety and Health ( agreement no. Y1-ES0001)
and NIOSH/CDC R01 OH 008795.
NR 52
TC 13
Z9 15
U1 0
U2 12
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 2012
VL 129
IS 1
BP 166
EP 173
DI 10.1093/toxsci/kfs183
PG 8
WC Toxicology
SC Toxicology
GA 998JN
UT WOS:000308234000015
PM 22610343
ER
PT J
AU Makuria, AT
Raghuraman, S
Burbelo, PD
Cantilena, CC
Allison, RD
Gibble, J
Rehermann, B
Alter, HJ
AF Makuria, Addisalem T.
Raghuraman, Sukanya
Burbelo, Peter D.
Cantilena, Cathy C.
Allison, Robert D.
Gibble, Joan
Rehermann, Barbara
Alter, Harvey J.
TI The clinical relevance of persistent recombinant immunoblot
assay-indeterminate reactions: insights into the natural history of
hepatitis C virus infection and implications for donor counseling
SO TRANSFUSION
LA English
DT Article
ID BLOOD-DONORS; IMMUNE-RESPONSES; LIVER-DISEASE; NON-A; NON-B; HCV;
EPIDEMIOLOGY; TRANSMISSION
AB BACKGROUND: Recombinant immunoblot assay (RIBA) is used to determine the specificity of antibody to hepatitis C virus (anti-HCV). The RIBA result is recorded as positive, negative, or indeterminate. The interpretation and significance of RIBA-indeterminate reactions are unclear. We addressed the clinical relevance of these reactions in the context of the natural history of HCV infection in a prospectively followed cohort of anti-HCVpositive blood donors. STUDY DESIGN AND METHODS: Donor demographics, exposure history, and humoral and cell-mediated immunity (CMI) were compared in 15 RIBA-indeterminate subjects, nine chronic HCV carriers, and eight spontaneously recovered subjects. Serum samples were tested for anti-HCV by a quantitative, liquid luciferase immunoprecipitation system (LIPS). CMI was assessed by interferon-? enzyme-linked immunosorbent spot assay. RESULTS: In the LIPS assay, the sum of antibody responses to six HCV antigens showed significant (p < 0.001) stepwise diminution progressing from chronic carriers to spontaneously recovered to RIBA-indeterminate subjects. CMI responses in RIBA-indeterminate subjects were similar to spontaneously recovered subjects and greater than chronic carriers and controls (p < 0.008). A parenteral risk factor was identified in only 13% of RIBA-indeterminate subjects compared to 89% of chronic carriers and 87% of spontaneously recovered subjects. RIBA-indeterminate donors were older than the other groups. CONCLUSION: The CMI and LIPS results suggest that persistent RIBA-indeterminate reactions represent waning anti-HCV responses in persons who have recovered from a remote HCV infection. In such cases, detectable antibody may ultimately disappear leaving no residual serologic evidence of prior HCV infection, as reported in a minority of long-term HCV-recovered subjects.
C1 [Alter, Harvey J.] NIDDK, NIH, Dept Transfus Med, Infect Dis Sect,Immunol Sect, Bethesda, MD 20892 USA.
Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, NIH, US Dept HHS, Bethesda, MD USA.
Greater Chesapeake & Potomac Reg Amer Red Cros, Baltimore, MD USA.
RP Alter, HJ (reprint author), NIDDK, NIH, Dept Transfus Med, Infect Dis Sect,Immunol Sect, Bldg 10,Room 1C-711,10 Ctr Dr, Bethesda, MD 20892 USA.
EM halter@dtm.cc.nih.gov
OI Allison, Robert/0000-0001-8458-5250
FU Division of Intramural Research; NIDDK; NIDCR; Clinical Center, NIH
FX This research was supported by the Division of Intramural Research,
NIDDK, NIDCR, and the Clinical Center, NIH.
NR 25
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U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2012
VL 52
IS 9
BP 1940
EP 1948
DI 10.1111/j.1537-2995.2011.03524.x
PG 9
WC Hematology
SC Hematology
GA 000OY
UT WOS:000308397400014
PM 22304422
ER
PT J
AU Flegel, WA
Denomme, GA
AF Flegel, Willy A.
Denomme, Gregory A.
TI Allo- and autoanti-D in weak D types and in partial D
SO TRANSFUSION
LA English
DT Letter
C1 [Flegel, Willy A.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Denomme, Gregory A.] Blood Ctr SE Wisconsin Inc, Serv Immunohematol, Milwaukee, WI 53233 USA.
[Denomme, Gregory A.] Blood Ctr SE Wisconsin Inc, Transfus Serv, Milwaukee, WI 53233 USA.
RP Flegel, WA (reprint author), NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
EM bill.flegel@nih.gov
NR 0
TC 2
Z9 2
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2012
VL 52
IS 9
BP 2068
EP 2069
DI 10.1111/j.15372995.2012.03693.x
PG 3
WC Hematology
SC Hematology
GA 000OY
UT WOS:000308397400032
ER
PT J
AU Van Laethem, F
Tikhonova, AN
Singer, A
AF Van Laethem, Francois
Tikhonova, Anastasia N.
Singer, Alfred
TI MHC restriction is imposed on a diverse T cell receptor repertoire by
CD4 and CD8 co-receptors during thymic selection
SO TRENDS IN IMMUNOLOGY
LA English
DT Review
ID MAJOR HISTOCOMPATIBILITY COMPLEX; ALPHA-BETA; KINASE P56LCK;
AMINO-ACIDS; CLASS-I; RECOGNITION; PEPTIDE; THYMOCYTES; PROTEIN;
SPECIFICITY
AB Mature alpha beta T cells recognize foreign antigenic peptides presented by MHC molecules but do not recognize native antigenic proteins; features known as MHC restriction. How MHC restriction is imposed on alpha beta T cells has intrigued immunologists for several decades. One model proposes that germline-encoded elements in the T cell receptor (TCR) variable regions are evolutionarily conserved to only recognize MHC. However, we propose an alternative model that posits that MHC restriction is imposed by CD4 and CD8 co-receptors during thymic selection. Thus, we think that TCRs are structurally able to recognize a huge diversity of ligands but only TCRs with MHC specificity survive thymic selection.
C1 [Van Laethem, Francois; Tikhonova, Anastasia N.; Singer, Alfred] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
RP Singer, A (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM singera@nih.gov
RI Tikhonova, Anastasia/F-1186-2015
FU Intramural Research Program of the NIH, NCI, Center for Cancer Research
FX We thank Hyun Park for critically reviewing the manuscript. This
research was supported by the Intramural Research Program of the NIH,
NCI, Center for Cancer Research.
NR 33
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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 2012
VL 33
IS 9
BP 437
EP 441
DI 10.1016/j.it.2012.05.006
PG 5
WC Immunology
SC Immunology
GA 005VP
UT WOS:000308778500002
PM 22771139
ER
PT J
AU McIntyre, JC
Davis, EE
Joiner, A
Williams, CL
Tsai, IC
Jenkins, PM
McEwen, DP
Zhang, L
Escobado, J
Thomas, S
Szymanska, K
Johnson, CA
Beales, PL
Green, ED
Mullikin, JC
Sabo, A
Muzny, DM
Gibbs, RA
Attie-Bitach, T
Yoder, BK
Reed, RR
Katsanis, N
Martens, JR
AF McIntyre, Jeremy C.
Davis, Erica E.
Joiner, Ariell
Williams, Corey L.
Tsai, I-Chun
Jenkins, Paul M.
McEwen, Dyke P.
Zhang, Lian
Escobado, John
Thomas, Sophie
Szymanska, Katarzyna
Johnson, Colin A.
Beales, Philip L.
Green, Eric D.
Mullikin, James C.
Sabo, Aniko
Muzny, Donna M.
Gibbs, Richard A.
Attie-Bitach, Tania
Yoder, Bradley K.
Reed, Randall R.
Katsanis, Nicholas
Martens, Jeffrey R.
CA NISC Comparative Sequencing Prog
TI Gene therapy rescues cilia defects and restores olfactory function in a
mammalian ciliopathy model
SO NATURE MEDICINE
LA English
DT Article
ID BARDET-BIEDL-SYNDROME; INTRAFLAGELLAR TRANSPORT PROTEIN; POLYCYSTIC
KIDNEY-DISEASE; SENSORY NEURONS; MOUSE MODEL; MUTATIONS; ANOSMIA;
DEGENERATION; EXPRESSION; SURVIVAL
AB Cilia are evolutionarily conserved microtubule-based organelles that are crucial for diverse biological functions, including motility, cell signaling and sensory perception(1). In humans, alterations in the formation and function of cilia manifest clinically as ciliopathies, a growing class of pleiotropic genetic disorders(2-4). Despite the substantial progress that has been made in identifying genes that cause ciliopathies, therapies for these disorders are not yet available to patients. Although mice with a hypomorphic mutation in the intraflagellar transport protein IFT88 (Ift88(Tg737Rpw) mice, also known as ORPK mice)(5) have been well studied, the relevance of IFT88 mutations to human pathology is unknown. We show that a mutation in IFT88 causes a hitherto unknown human ciliopathy. In vivo complementation assays in zebrafish and mIMCD3 cells show the pathogenicity of this newly discovered allele. We further show that ORPK mice are functionally anosmic as a result of the loss of cilia on their olfactory sensory neurons (OSNs). Notably, adenoviral-mediated expression of IFT88 in mature, fully differentiated OSNs of ORPK mice is sufficient to restore ciliary structures and rescue olfactory function. These studies are the first to use in vivo therapeutic treatment to reestablish cilia in a mammalian ciliopathy. More broadly, our studies indicate that gene therapy is a viable option for cellular and functional rescue of the complex ciliary organelle in established differentiated cells.
C1 [McIntyre, Jeremy C.; Joiner, Ariell; Williams, Corey L.; Jenkins, Paul M.; McEwen, Dyke P.; Zhang, Lian; Escobado, John; Martens, Jeffrey R.] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA.
[Davis, Erica E.; Tsai, I-Chun; Katsanis, Nicholas] Duke Univ, Med Ctr, Ctr Human Dis Modeling, Durham, NC USA.
[Davis, Erica E.; Katsanis, Nicholas] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA.
[Davis, Erica E.; Tsai, I-Chun; Katsanis, Nicholas] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA.
[Thomas, Sophie; Attie-Bitach, Tania] Univ Paris 05, Dept Genet, Paris, France.
[Thomas, Sophie; Attie-Bitach, Tania] Univ Paris 05, Hop Necker Enfants Malad, INSERM, U781, Paris, France.
[Szymanska, Katarzyna; Johnson, Colin A.] St James Univ Hosp, Leeds Inst Mol Med, Sect Ophthalmol & Neurosci, Leeds, W Yorkshire, England.
[Beales, Philip L.] UCL, Mol Med Unit, Inst Child Hlth, London, England.
[Green, Eric D.; Mullikin, James C.; NISC Comparative Sequencing Prog] NHGRI, US Natl Inst Hlth Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA.
[Yoder, Bradley K.] Univ Alabama Birmingham, Dept Cell Biol, Birmingham, AL USA.
[Sabo, Aniko; Muzny, Donna M.; Gibbs, Richard A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[Reed, Randall R.] Johns Hopkins Univ, Dept Mol Biol & Genet, Baltimore, MD USA.
RP Martens, JR (reprint author), Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA.
EM martensj@umich.edu
RI Katsanis, Nicholas/E-1837-2012; Jenkins, Paul/C-9098-2015;
OI Jenkins, Paul/0000-0002-4207-5823; Katsanis,
Nicholas/0000-0002-2480-0171
FU US National Institutes of Health [R01DC009606, F32DC011990, R01DC004553,
R01DC008295, R01DK75996, R01EY021872, R01HD04260, R01DK072301,
R01DK075972]; l'Agence National pour la Recherche (ANR) [2010
FOETOCILPATH 1122 01]; University of Alabama at Birmingham Hepatorenal
Fibrocystic Disease Core Center [DK074083]; European Community's Seventh
Framework Programme [241955]
FX This work was support by US National Institutes of Health grants
R01DC009606 (J.R.M.), F32DC011990 (J.C.M.), R01DC004553, R01DC008295
(R.R.R.), R01DK75996 (B.K.Y.), R01EY021872 (E.E.D.), R01HD04260,
R01DK072301 and R01DK075972 (N.K.), by l'Agence National pour la
Recherche (ANR) 2010 FOETOCILPATH 1122 01 (T.A.-B.) and by the
University of Alabama at Birmingham Hepatorenal Fibrocystic Disease Core
Center (DK074083). E.E.D., C.A.J., P.L.B. and N.K. are supported by the
European Community's Seventh Framework Programme FP7/2009 under grant
agreement 241955, SYSCILIA. N.K. is a Distinguished Jean and George W.
Brumley Professor. We thank P. Loget for referring the family for this
study, S. Dugan-Rocha, U. Nagaswamy and A. Hawes for assistance with
mutational screening and R. Margolskee (Mount Sinai School of Medicine
of New York University) for providing antibodies.
NR 40
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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 2012
VL 18
IS 9
BP 1423
EP +
DI 10.1038/nm.2860
PG 7
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 001PJ
UT WOS:000308472300040
PM 22941275
ER
PT J
AU Pletnev, S
Pletneva, NV
Souslova, EA
Chudakov, DM
Lukyanov, S
Wlodawer, A
Dauter, Z
Pletnev, V
AF Pletnev, Sergei
Pletneva, Nadya V.
Souslova, Ekaterina A.
Chudakov, Dmitry M.
Lukyanov, Sergey
Wlodawer, Alexander
Dauter, Zbigniew
Pletnev, Vladimir
TI Structural basis for bathochromic shift of fluorescence in far-red
fluorescent proteins eqFP650 and eqFP670
SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
LA English
DT Article
ID WHOLE-BODY; ENTACMAEA-QUADRICOLOR; CRYSTAL-STRUCTURE; CHROMOPHORE;
ISOMERIZATION; MICROSCOPY; VARIANTS; EMISSION; BLUE
AB The crystal structures of the far-red fluorescent proteins (FPs) eqFP650 (lambda(max)(ex)/lambda(max)(em) 592/650 nm) and eqFP670 (lambda(max)(ex)/lambda(max)(em) 605/670 nm), the successors of the far-red FP Katushka (lambda(max)(ex)/lambda(max)(em) 588/635 nm), have been determined at 1.8 and 1.6 angstrom resolution, respectively. An examination of the structures demonstrated that there are two groups of changes responsible for the bathochromic shift of excitation/emission bands of these proteins relative to their predecessor. The first group of changes resulted in an increase of hydrophilicity at the acylimine site of the chromophore due to the presence of one and three water molecules in eqFP650 and eqFP670, respectively. These water molecules provide connection of the chromophore with the protein scaffold via hydrogen bonds causing an similar to 15 nm bathochromic shift of the eqFP650 and eqFP670 emission bands. The second group of changes observed in eqFP670 arises from substitution of both Ser143 and Ser158 by asparagines. Asn143 and Asn158 of eqFP670 are hydrogen bonded with each other, as well as with the protein scaffold and with the p-hydroxyphenyl group of the chromophore, resulting in an additional similar to 20 nm bathochromic shift of the eqFP670 emission band as compared to eqFP650. The role of the observed structural changes was verified by mutagenesis.
C1 [Pletnev, Sergei; Dauter, Zbigniew] NCI, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, Argonne, IL 60439 USA.
[Pletnev, Sergei] SAIC Frederick, Basic Res Program, Argonne, IL 60439 USA.
[Pletneva, Nadya V.; Souslova, Ekaterina A.; Chudakov, Dmitry M.; Lukyanov, Sergey; Pletnev, Vladimir] Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia.
[Lukyanov, Sergey] Nizhny Novgorod State Med Acad, Nizhnii Novgorod, Russia.
[Wlodawer, Alexander] NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP Pletnev, S (reprint author), NCI, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, Argonne, IL 60439 USA.
EM pletnevs@mail.nih.gov
RI Chudakov, Dmitriy/G-7741-2014; Pletneva, Nadya/F-7839-2014; Pletnev,
Vladimir/Q-6151-2016
OI Chudakov, Dmitriy/0000-0003-0430-790X;
FU US Department of Energy, Office of Science, Office of Basic Energy
Sciences [W-31-109-Eng-38]; Frederick National Laboratory for Cancer
Research; National Institutes of Health (NIH) [HHSN261200800001E]; NIH;
Frederick National Laboratory, Center for Cancer Research; Russian
Federation [MK-539.2011.4]; Russian Foundation for Basic Research
[11-04-00241]; Russian Ministry of Education and Science
[16.740.11.0367, 16.512.11.2139]; Russian Academy of Sciences; Measures
to Attract Leading Scientists to Russian Educational Institutions
[11.G34.31.0017]
FX Diffraction data were collected at the SER-CAT ID22 beamline at the
Advanced Photon Source, Argonne National Laboratory. Use of the Advanced
Photon Source 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 funded in part with Federal funds
from the Frederick National Laboratory for Cancer Research, National
Institutes of Health (NIH) contract No. HHSN261200800001E, and the
Intramural Research Program of the NIH, Frederick National Laboratory,
Center for Cancer Research, by grants from the President of the Russian
Federation (No. MK-539.2011.4), the Russian Foundation for Basic
Research (No. 11-04-00241), the Russian Ministry of Education and
Science (Nos. 16.740.11.0367 and 16.512.11.2139), the Molecular and Cell
Biology program of the Russian Academy of Sciences and Measures to
Attract Leading Scientists to Russian Educational Institutions (No.
11.G34.31.0017). 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.
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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 2012
VL 68
BP 1088
EP 1097
DI 10.1107/S0907444912020598
PN 9
PG 10
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biophysics; Crystallography
SC Biochemistry & Molecular Biology; Biophysics; Crystallography
GA 999QT
UT WOS:000308330000003
PM 22948909
ER
PT J
AU van den Borst, B
Gosker, HR
Koster, A
Yu, BB
Kritchevsky, SB
Liu, YM
Meibohm, B
Rice, TB
Shlipak, M
Yende, S
Harris, TB
Schols, AMWJ
AF van den Borst, Bram
Gosker, Harry R.
Koster, Annemarie
Yu, Binbing
Kritchevsky, Stephen B.
Liu, Yongmei
Meibohm, Bernd
Rice, Thomas B.
Shlipak, Michael
Yende, Sachin
Harris, Tamara B.
Schols, Annemie M. W. J.
CA Hlth Aging & Body Composit Hlth AB
TI The influence of abdominal visceral fat on inflammatory pathways and
mortality risk in obstructive lung disease
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID CHRONIC HEART-FAILURE; CHRONIC KIDNEY-DISEASE; PULMONARY-DISEASE;
ADIPOSE-TISSUE; SYSTEMIC INFLAMMATION; PLASMA ADIPONECTIN; METABOLIC
SYNDROME; PHYSICAL-ACTIVITY; ELDERLY SUBJECTS; OLDER-ADULTS
AB Background: Low-grade systemic inflammation, particularly elevated IL-6, predicts mortality in chronic obstructive pulmonary disease (COPD). Although altered body composition, especially increased visceral fat (VF) mass, could be a significant contributor to low-grade systemic inflammation, this remains unexplored in COPD.
Objective: The objective was to investigate COPD-specific effects on VF and plasma adipocytokines and their predictive value for mortality.
Design: Within the Health, Aging, and Body Composition (Health ABC) Study, an observational study in community-dwelling older persons, we used propensity scores to match n = 729 persons with normal lung function to n = 243 persons with obstructive lung disease (OLD; defined as the ratio of forced expiratory volume in 1 s to forced vital capacity < lower limit of normal). Matching was based on age, sex, race, clinic site, BMI, and smoking status. Within this well-balanced match, we compared computed tomography acquired visceral fat area (VFA) and plasma adipocytokines, analyzed independent associations of VFA and OLD status on plasma adipocytokines, and studied their predictive value for 9.4-y mortality.
Results: Whereas whole-body fat mass was comparable between groups, persons with OLD had increased VFA and higher plasma IL-6, adiponectin, and plasminogen activator inhibitor 1 (PAI-1). Both OLD status and VFA were independently positively associated with IL-6. Adiponectin was positively associated with OLD status but negatively associated with VFA. PAI-1 was no longer associated with OLD status after VFA was accounted for. Participants with OLD had increased risk of all-cause, respiratory, and cardiovascular mortality, of which IL-6 was identified as an independent predictor.
Conclusion: Our data suggest that excessive abdominal visceral fat contributes to increased plasma IL-6, which, in turn, is strongly associated with all-cause and cause-specific mortality in older persons with OLD. Am J Clin Nutr 2012;96:516-26.
C1 [van den Borst, Bram; Gosker, Harry R.; Schols, Annemie M. W. J.] Maastricht Univ, Med Ctr, NUTRIM Sch Nutr Toxicol & Metab, Dept Resp Med, NL-6200 MD Maastricht, Netherlands.
[Koster, Annemarie; Yu, Binbing; Harris, Tamara B.] NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Koster, Annemarie] Maastricht Univ, Med Ctr, Dept Social Med, Sch Publ Hlth & Primary Care, Maastricht, Netherlands.
[Kritchevsky, Stephen B.] Wake Forest Sch Med, Sticht Ctr Aging, Winston Salem, NC 27109 USA.
[Liu, Yongmei] Wake Forest Univ, Sch Med, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC 27109 USA.
[Meibohm, Bernd] Univ Tennessee, Ctr Hlth Sci, Dept Pharmaceut Sci, Memphis, TN 38163 USA.
[Rice, Thomas B.] Univ Pittsburgh, Med Ctr, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA.
[Shlipak, Michael] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Shlipak, Michael] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA.
[Shlipak, Michael] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA.
[Yende, Sachin] Univ Pittsburgh, CRISMA Ctr, Pittsburgh, PA USA.
[Yende, Sachin] Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA USA.
RP van den Borst, B (reprint author), Maastricht Univ, Med Ctr, NUTRIM Sch Nutr Toxicol & Metab, Dept Resp Med, POB 616, NL-6200 MD Maastricht, Netherlands.
EM b.vdborst@maastrichtuniversity.nl
RI Koster, Annemarie/E-7438-2010;
OI Kritchevsky, Stephen/0000-0003-3336-6781; Gosker,
Harry/0000-0002-7659-0225
FU Dutch Top Institute Pharma [T1-201]; National Institute on Aging (NIA)
[N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050]; National
Institute of Nursing Research [T01-NR012459]; NIH, NIA
FX This study was performed within the framework of the Dutch Top Institute
Pharma project T1-201. Top Institute Pharma approved the manuscript.;
Supported by the National Institute on Aging (NIA) contracts
N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106; NIA grant R01-AG028050; and
National Institute of Nursing Research grant T01-NR012459. This research
was supported in part by the Intramural Research Program of the NIH,
NIA.
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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 2012
VL 96
IS 3
BP 516
EP 526
DI 10.3945/ajcn.112.040774
PG 11
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 993MM
UT WOS:000307863800010
PM 22811442
ER
PT J
AU Kant, AK
Graubard, BI
AF Kant, Ashima K.
Graubard, Barry I.
TI Race-ethnic, family income, and education differentials in nutritional
and lipid biomarkers in US children and adolescents: NHANES 2003-2006
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID 3RD NATIONAL-HEALTH; CARDIOVASCULAR RISK-FACTORS; FOLIC-ACID
FORTIFICATION; SOCIAL-CLASS GRADIENTS; VITAMIN-D DEFICIENCY;
UNITED-STATES; ALPHA-TOCOPHEROL; SERUM CONCENTRATIONS; AFRICAN-AMERICAN;
YOUNG-ADULTS
AB Background: Children from ethnic minority and low-income families in the United States have higher rates of poor health and higher mortality rates. Diet, an acknowledged correlate of health, may mediate the known race-ethnic and socioeconomic differentials in the health of US children.
Objective: The objective was to examine the independent association of race-ethnicity, family income, and education with nutritional and lipid biomarkers in US children.
Design: We used data from the NHANES 2003-2006 to examine serum concentrations of vitamins A, D, E, C, B-6, and B-12; serum concentrations of folate, carotenoids, and lipids; and dietary intakes of corresponding nutrients for 2-19-y-old children (n = similar to 2700-7500). Multiple covariate adjusted regression methods were used to examine the independent and joint. associations of race-ethnicity, family income, and education with biomarker status.
Results: Non-Hispanic blacks had lower mean serum concentrations of vitamins A, B-6, and E and a-carotene than did non-Hispanic whites. Both non-Hispanic blacks and Mexican Americans had higher mean serum vitamin C, beta-cryptoxanthin, and lutein + zeaxanthin but lower folate and vitamin D concentrations compared with non-Hispanic whites. In comparison with non-Hispanic whites, non-Hispanic blacks were less likely to have low serum HDL cholesterol or high triglycerides. Family income and education predicted few biomarker or dietary outcomes, and the observed associations were weak. Moreover, modification of race-ethnic differentials by income or education (or vice versa) was noted for very few biomarkers.
Conclusion: Race-ethnicity, but not family income or education, was a strong independent predictor of serum nutrient concentrations and dietary micronutrient intakes in US children and adolescents. Am J Clin Nutr 2012;96:601-12.
C1 [Kant, Ashima K.] CUNY Queens Coll, Dept Family Nutr & Exercise Sci, Flushing, NY 11367 USA.
[Graubard, Barry I.] NCI, Div Canc Epidemiol & Genet, Biostat Branch, NIH, Bethesda, MD 20892 USA.
RP Kant, AK (reprint author), CUNY Queens Coll, Dept Family Nutr & Exercise Sci, Remsen Hall,Room 306E, Flushing, NY 11367 USA.
EM ashima.kant@qc.cuny.edu
FU NIH [HD060217]; Department of Health and Human Services, National Cancer
Institute, NIH
FX Supported in part by an NIH grant award (HD060217) (AKK), a Professional
Staff Congress-CUNY research grant award (AKK), and the intramural
research program of the Department of Health and Human Services,
National Cancer Institute, NIH (BIG).
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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 2012
VL 96
IS 3
BP 601
EP 612
DI 10.3945/ajcn.112.035535
PG 12
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 993MM
UT WOS:000307863800020
PM 22836030
ER
PT J
AU Sylvetsky, AC
Welsh, JA
Brown, RJ
Vos, MB
AF Sylvetsky, Allison C.
Welsh, Jean A.
Brown, Rebecca J.
Vos, Miriam B.
TI Low-calorie sweetener consumption is increasing in the United States
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID PREVALENCE; CHILDREN
AB Background: Low-calorie and no-calorie sweeteners (LCSs) have emerged as alternatives to added sugars. Research suggests that consumption among all Americans is increasing, yet it is unknown whether consumption trends differ among population subgroups.
Objective: Our study aimed to assess recent national trends in LCS consumption among children and other demographic subgroups in the United States.
Design: We used NHANES data collected in five 2-y cycles from 1999-2000 to 2007-2008. Consumption of foods and beverages with LCSs was estimated by using one 24-h dietary recall. Estimates of the proportion of the population consuming foods and beverages containing LCSs (prevalence of consumption) were weighted to obtain nationally representative results. Trends in prevalence of LCS consumption and mean intake of beverages sweetened with LCSs were tested by using chi-square tests for trend and F tests.
Results: In 2007-2008, the percentage of children and adults consuming foods and beverages containing LCSs increased. The prevalence of consuming beverages with LCSs increased from 6.1% to 12.5% among children (P-trend < 0.0001) and from 18.7% to 24.1% among adults (P < 0.001). Increases in the prevalence of consumption of calorie-containing beverages with LCSs were observed among all weight, age, socioeconomic, and race-ethnicity subgroups in both children and adults. However, little change in consumption of no-calorie beverages with LCSs or LCS-containing foods was found.
Conclusions: The consumption of LCS-containing beverages has doubled among US children over the past decade. Further research is needed to understand the health effects of this trend. Am J Clin Nutr 2012;96:640-6.
C1 [Sylvetsky, Allison C.] NIDDK, DEOB, NIH, Bethesda, MD 20892 USA.
[Sylvetsky, Allison C.] Emory Univ, Div Biol & Biomed Sci, Nutr & Hlth Sci Program, Laney Grad Sch, Atlanta, GA 30322 USA.
[Welsh, Jean A.; Vos, Miriam B.] Emory Univ, Dept Pediat, Atlanta, GA 30322 USA.
[Vos, Miriam B.] Childrens Healthcare Atlanta, Atlanta, GA USA.
RP Sylvetsky, AC (reprint author), NIDDK, DEOB, NIH, Bldg 10,7C432A,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM asylvet@emory.edu
FU NIH; NIDDK; NIH, NIDDK [K23DK0809530]
FX Supported in part by the Intramural Research Program of the NIH and the
NIDDK and by a grant from the NIH, NIDDK (grant K23DK0809530 to MBV).
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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 2012
VL 96
IS 3
BP 640
EP 646
DI 10.3945/ajcn.112.034751
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 993MM
UT WOS:000307863800024
PM 22854409
ER
PT J
AU Tang, GW
Hu, YM
Yin, SA
Wang, Y
Dallal, GE
Grusak, MA
Russell, RM
AF Tang, Guangwen
Hu, Yuming
Yin, Shi-an
Wang, Yin
Dallal, Gerard E.
Grusak, Michael A.
Russell, Robert M.
TI beta-Carotene in Golden Rice is as good as beta-carotene in oil at
providing vitamin A to children (Retracted article. See vol. 102, pg.
715, 2015)
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article; Retracted Publication
ID ISOTOPE REFERENCE METHOD; INTESTINAL ABSORPTION; CHINESE ADULTS;
BIOEFFICACY; VEGETABLES; EQUIVALENCE; DEFICIENCY; PROVITAMIN;
CONVERSION; INDONESIA
AB Background: Golden Rice (GR) has been genetically engineered to be rich in beta-carotene for use as a source of vitamin A.
Objective: The objective was to compare the vitamin A value of beta-carotene in GR and in spinach with that of pure beta-carotene in oil when consumed by children.
Design: Children (n = 68; age 6-8 y) were randomly assigned to consume GR or spinach (both grown in a nutrient solution containing 23 atom% (H2O)-H-2) or [H-2(8)]beta-carotene in an oil capsule. The GR and spinach beta-carotene were enriched with deuterium (H-2) with the highest abundance molecular mass (M) at M beta+C+H-2(10). [C-13(10)]Retinyl acetate in an oil capsule was administered as a reference dose. Serum samples collected from subjects were analyzed by using gas chromatography electron-capture negative chemical ionization mass spectrometry for the enrichments of labeled retinol: M-retinol+4 (from [H-2(8)]beta-carotene in oil), M-retinol+5 (from GR or spinach [H-2(10)]beta-carotene), and M-retinol+10 (from [C-13(10)]retinyl acetate).
Results: Using the response to the dose of [C-13(10)]retinyl acetate (0.5 mg) as a reference, our results (with the use of AUC of molar enrichment at days 1, 3, 7, 14, and 21 after the labeled doses) showed that the conversions of pure beta-carotene (0.5 mg), GR beta-carotene (0.6 mg), and spinach beta-carotene (1.4 mg) to retinol were 2.0, 2.3, and 7.5 to 1 by weight, respectively.
Conclusions: The beta-carotene in GR is as effective as pure beta-carotene in oil and better than that in spinach at providing vitamin A to children. A bowl of similar to 100 to 150 g cooked GR (50 g dry weight) can provide similar to 60% of the Chinese Recommended Nutrient Intake of vitamin A for 6-8-y-old children. This trial was registered at www.clinicaltrials.gov as NCT00680212. Am J Clin Nutr 2012;96:658-64.
C1 [Tang, Guangwen; Dallal, Gerard E.; Russell, Robert M.] Tufts Univ, USDA, Human Nutr Res Ctr Aging, Carotenoids & Hlth Lab, Boston, MA 02111 USA.
[Hu, Yuming] Hunan Prov Ctr Dis Control & Prevent, Changsha, Hunan, Peoples R China.
[Yin, Shi-an] Natl Inst Nutr & Food Safety, Beijing, Peoples R China.
[Wang, Yin] Zhejiang Acad Med Sci, Hangzhou, Zhejiang, Peoples R China.
[Grusak, Michael A.] Baylor Coll Med, Dept Pediat, ARS, USDA,Childrens Nutr Res Ctr, Houston, TX 77030 USA.
[Russell, Robert M.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
RP Tang, GW (reprint author), Tufts Univ, Jean Mayer USDA, Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA.
EM guangwen.tang@tufts.edu
FU US Department of Agriculture [581950-9-001, 58-6250-6-001,
581950-7-707]; National Institute of Diabetes and Digestive and Kidney
Diseases, NIH [NIDDK DK620021]; National Technology Research and
Development Program in the 11th Five Year Plan of China [2008BAI58B03]
FX This material is based on work supported by the US Department of
Agriculture under Cooperative Agreements 581950-9-001, 58-6250-6-001,
and 581950-7-707; by a grant from the National Institute of Diabetes and
Digestive and Kidney Diseases, NIH (NIDDK DK620021); and by a grant on
spinach and pure labeled beta-carotene from the National Technology
Research and Development Program in the 11th Five Year Plan of China
(2008BAI58B03).
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PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
EI 1938-3207
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD SEP
PY 2012
VL 96
IS 3
BP 658
EP 664
DI 10.3945/ajcn.111.030775
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 993MM
UT WOS:000307863800026
PM 22854406
ER
PT J
AU Koushik, A
Spiegelman, D
Albanes, D
Anderson, KE
Bernstein, L
van den Brandt, PA
Bergkvist, L
English, DR
Freudenheim, JL
Fuchs, CS
Genkinger, JM
Giles, GG
Goldbohm, RA
Horn-Ross, PL
Mannisto, S
McCullough, ML
Millen, AE
Miller, AB
Robien, K
Rohan, TE
Schatzkin, A
Shikany, JM
Stolzenberg-Solomon, RZ
Willett, WC
Wolk, A
Ziegler, RG
Smith-Warner, SA
AF Koushik, Anita
Spiegelman, Donna
Albanes, Demetrius
Anderson, Kristin E.
Bernstein, Leslie
van den Brandt, Piet A.
Bergkvist, Leif
English, Dallas R.
Freudenheim, Jo L.
Fuchs, Charles S.
Genkinger, Jeanine M.
Giles, Graham G.
Goldbohm, R. Alexandra
Horn-Ross, Pamela L.
Mannisto, Satu
McCullough, Marjorie L.
Millen, Amy E.
Miller, Anthony B.
Robien, Kim
Rohan, Thomas E.
Schatzkin, Arthur
Shikany, James M.
Stolzenberg-Solomon, Rachael Z.
Willett, Walter C.
Wolk, Alicja
Ziegler, Regina G.
Smith-Warner, Stephanie A.
TI Intake of Fruits and Vegetables and Risk of Pancreatic Cancer in a
Pooled Analysis of 14 Cohort Studies
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Review
DE diet; fruit; pancreatic neoplasms; prospective studies; vegetables
ID FOOD-FREQUENCY QUESTIONNAIRE; PAST MEDICAL HISTORY; UNITED-STATES;
ALCOHOL-CONSUMPTION; REGRESSION-MODELS; MEASUREMENT-ERROR; GLYCEMIC
INDEX; LIFE-STYLE; EXOCRINE PANCREAS; DIETARY PATTERNS
AB Fruit and vegetable intake may protect against pancreatic cancer, since fruits and vegetables are rich in potentially cancer-preventive nutrients. Most case-control studies have found inverse associations between fruit and vegetable intake and pancreatic cancer risk, although bias due to reporting error cannot be ruled out. In most prospective studies, inverse associations have been weaker and imprecise because of small numbers of cases. The authors examined fruit and vegetable intake in relation to pancreatic cancer risk in a pooled analysis of 14 prospective studies from North America, Europe, and Australia (study periods between 1980 and 2005). Relative risks and 2-sided 95 confidence intervals were estimated separately for the 14 studies using the Cox proportional hazards model and were then pooled using a random-effects model. Of 862,584 men and women followed for 720 years, 2,212 developed pancreatic cancer. The pooled multivariate relative risks of pancreatic cancer per 100-g/day increase in intake were 1.01 (95 confidence interval (CI): 0.99, 1.03) for total fruits and vegetables, 1.01 (95 CI: 0.99, 1.03) for total fruits, and 1.02 (95 CI: 0.99, 1.06) for total vegetables. Associations were similar for men and women separately and across studies. These results suggest that fruit and vegetable intake during adulthood is not associated with a reduced pancreatic cancer risk.
C1 [Koushik, Anita] Univ Montreal, Hosp Res Ctr CRCHUM, Montreal, PQ H2W 1V1, Canada.
[Koushik, Anita] Univ Montreal, Dept Social & Prevent Med, Fac Med, Montreal, PQ H2W 1V1, Canada.
[Spiegelman, Donna; Willett, Walter C.; Smith-Warner, Stephanie A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Spiegelman, Donna; Willett, Walter C.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Spiegelman, Donna; Willett, Walter C.] Harvard Univ, Sch Med, Boston, MA USA.
[Albanes, Demetrius; Schatzkin, Arthur; Stolzenberg-Solomon, Rachael Z.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Anderson, Kristin E.; Robien, Kim] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Anderson, Kristin E.; Robien, Kim] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN USA.
[Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Div Canc Etiol, Dept Populat Sci, Duarte, CA 91010 USA.
[van den Brandt, Piet A.] Maastricht Univ Med Ctr, Dept Epidemiol, GROW Sch Oncol & Dev Biol, Maastricht, Netherlands.
[Bergkvist, Leif] Cent Hosp Vasteras, Dept Surg, Vasteras, Sweden.
[Bergkvist, Leif] Cent Hosp Vasteras, Clin Res Ctr, Vasteras, Sweden.
[English, Dallas R.; Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Australia.
[English, Dallas R.; Giles, Graham G.] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia.
[Freudenheim, Jo L.; Millen, Amy E.] SUNY Buffalo, Dept Social & Prevent Med, Sch Publ Hlth & Hlth Profess, Buffalo, NY 14260 USA.
[Fuchs, Charles S.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA.
[Genkinger, Jeanine M.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA.
[Goldbohm, R. Alexandra] TNO Qual Life, Dept Prevent & Hlth Care, Leiden, Netherlands.
[Horn-Ross, Pamela L.] Canc Prevent Inst Calif, Fremont, CA USA.
[Mannisto, Satu] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[McCullough, Marjorie L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Miller, Anthony B.] Univ Toronto, Div Epidemiol, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Rohan, Thomas E.] Yeshiva Univ, Dept Epidemiol & Populat Hlth, Albert Einstein Coll Med, Bronx, NY USA.
[Ziegler, Regina G.] NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Shikany, James M.] Univ Alabama Birmingham, Sch Med, Div Prevent Med, Birmingham, AL USA.
[Willett, Walter C.; Smith-Warner, Stephanie A.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Wolk, Alicja] Karolinska Inst, Natl Inst Environm Med, Stockholm, Sweden.
RP Koushik, A (reprint author), Univ Montreal, Hosp Res Ctr CRCHUM, 3875 St Urbain St,3rd Floor, Montreal, PQ H2W 1V1, Canada.
EM anita.koushik@umontreal.ca
RI Albanes, Demetrius/B-9749-2015;
OI Mannisto, Satu/0000-0002-8668-3046; Robien, Kim/0000-0002-2120-2280;
Giles, Graham/0000-0003-4946-9099; English, Dallas/0000-0001-7828-8188
FU US National Cancer Institute [P01 CA55075]; Canadian Institutes of
Health Research
FX This work was supported by grant P01 CA55075 from the US National Cancer
Institute. Dr. Anita Koushik currently holds a New Investigator Award
from the Canadian Institutes of Health Research.
NR 81
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U1 0
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD SEP 1
PY 2012
VL 176
IS 5
BP 373
EP 386
DI 10.1093/aje/kws027
PG 14
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 998GX
UT WOS:000308226600002
PM 22875754
ER
PT J
AU Sesma, JI
Kreda, SM
Steinckwich-Besancon, N
Dang, H
Garcia-Mata, R
Harden, TK
Lazarowski, ER
AF Sesma, Juliana I.
Kreda, Silvia M.
Steinckwich-Besancon, Natacha
Dang, Hong
Garcia-Mata, Rafael
Harden, T. Kendall
Lazarowski, Eduardo R.
TI The UDP-sugar-sensing P2Y(14) receptor promotes Rho-mediated signaling
and chemotaxis in human neutrophils
SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
LA English
DT Article
DE purinergic receptors
ID PROTEIN-COUPLED RECEPTOR; ENDOTHELIAL-CELL MIGRATION; P2X(1) RECEPTOR;
GPR105 KIAA0001; P2Y14 RECEPTOR; ATP RELEASE; HL60 CELLS; ACTIVATION;
GLUCOSE; NUCLEOTIDE
AB Sesma JI, Kreda SM, Steinckwich-Besancon N, Dang H, Garcia-Mata R, Harden TK, Lazarowski ER. The UDP-sugar-sensing P2Y(14) receptor promotes Rho-mediated signaling and chemotaxis in human neutrophils. Am J Physiol Cell Physiol 303: C490-C498, 2012. First published June 6, 2012; doi:10.1152/ajpcell.00138.2012.-The G(i)-coupled P2Y(14) receptor (P2Y(14)-R) is potently activated by UDP-sugars and UDP. Although P2Y(14)-R mRNA is prominently expressed in circulating neutrophils, the signaling pathways and functional responses associated with this receptor are undefined. In this study, we illustrate that incubation of isolated human neutrophils with UDPglucose resulted in cytoskeleton rearrangement, change of cell shape, and enhanced cell migration. We also demonstrate that UDP-glucose promotes rapid, robust, and concentration-dependent activation of RhoA in these cells. Ecto-nucleotidases expressed on neutrophils rapidly hydrolyzed extracellular ATP, but incubation with UDPglucose for up to 1 h resulted in negligible metabolism of the nucleotide-sugar. HL60 human promyelocytic leukemia cells do not express the P2Y(14)-R, but neutrophil differentiation of HL60 cells with DMSO resulted in markedly enhanced P2Y(14)-R expression. Accordingly, UDP-glucose, UDP-galactose, and UDP-N-acetylglucosamine promoted Rho activation in differentiated but not in undifferentiated HL60 cells. Stable expression of recombinant human P2Y(14)-R conferred UDP-sugar-promoted responses to undifferentiated HL60 cells. UDP-glucose-promoted RhoA activation also was accompanied by enhanced cell migration in differentiated HL60 cells, and these responses were blocked by Rho kinase inhibitors. These results support the notion that UDP-glucose is a stable and potent proinflammatory mediator that promotes P2Y(14)-R-mediated neutrophil motility via Rho/Rho kinase activation.
C1 [Lazarowski, Eduardo R.] Univ N Carolina, Cyst Fibrosis Pulm Res & Treatment Ctr, Dept Med, Sch Med, Chapel Hill, NC 27599 USA.
[Garcia-Mata, Rafael] Univ N Carolina, Dept Cell & Dev Biol, Sch Med, Chapel Hill, NC 27599 USA.
[Harden, T. Kendall] Univ N Carolina, Dept Pharmacol, Sch Med, Chapel Hill, NC 27599 USA.
[Steinckwich-Besancon, Natacha] NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA.
RP Lazarowski, ER (reprint author), Univ N Carolina, Cyst Fibrosis Pulm Res & Treatment Ctr, Dept Med, Sch Med, 7017 Thurston Bowles Bldg,CB 7248, Chapel Hill, NC 27599 USA.
EM eduardo_lazarowski@med.unc.edu
OI Garcia-Mata, Rafael/0000-0002-7116-4411
FU National Institutes of Health [GM-38123, P01-HL-0343223]
FX Research from the authors' laboratories was supported by National
Institutes of Health Grants GM-38123 and P01-HL-0343223.
NR 57
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Z9 15
U1 1
U2 8
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6143
J9 AM J PHYSIOL-CELL PH
JI Am. J. Physiol.-Cell Physiol.
PD SEP
PY 2012
VL 303
IS 5
BP C490
EP C498
DI 10.1152/ajpcell.00138.2012
PG 9
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 001MZ
UT WOS:000308466100004
PM 22673622
ER
PT J
AU Chen, GZ
Xu, RF
Wang, YN
Wang, PH
Zhao, G
Xu, XZ
Gruzdev, A
Zeldin, DC
Wang, DW
AF Chen, Guangzhi
Xu, Renfan
Wang, Yinna
Wang, Peihua
Zhao, Gang
Xu, Xizhen
Gruzdev, Artiom
Zeldin, Darryl C.
Wang, Dao Wen
TI Genetic disruption of soluble epoxide hydrolase is protective against
streptozotocin-induced diabetic nephropathy
SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
LA English
DT Article
DE soluble epoxide hydrolase gene disruption; hk-2 cells; diabetic
nephropathy; epoxyeicosatrienoic acids
ID ACTIVATED PROTEIN-KINASE; NITRIC-OXIDE SYNTHASE; TUBULAR
EPITHELIAL-CELLS; HUMAN TISSUE KALLIKREIN; NECROSIS-FACTOR-ALPHA;
INSULIN-RESISTANCE; SIGNALING PATHWAYS; ENDOTHELIAL-CELLS; AKT
PHOSPHORYLATION; SKELETAL-MUSCLE
AB Chen G, Xu R, Wang Y, Wang P, Zhao G, Xu X, Gruzdev A, Zeldin DC, Wang DW. Genetic disruption of soluble epoxide hydrolase is protective against streptozotocin-induced diabetic nephropathy. Am J Physiol Endocrinol Metab 303: E563-E575, 2012. First published June 26, 2012; doi:10.1152/ajpendo.00591.2011.-Cytochrome P-450 (CYP) epoxygenases metabolize arachidonic acid into epoxyeicosatrienoic acids (EETs), which play important roles in regulating cardiovascular functions. The anti-inflammatory, antiapoptotic, proangiogenic, and antihypertensive properties of EETs suggest a beneficial role for EETs in diabetic nephropathy. Endogenous EET levels are maintained by a balance between synthesis by CYP epoxygenases and hydrolysis by epoxide hydrolases into physiologically less active dihydroxyeicosatrienoic acids. Genetic disruption of soluble epoxide hydrolase (sEH/EPHX2) results in increased EET levels through decreased hydrolysis. This study investigated the effects of sEH gene disruption on diabetic nephropathy in streptozotocin-induced diabetic mice. Streptozotocin-induced diabetic manifestations were attenuated in sEH-deficient mice relative to wild-type controls, with significantly decreased levels of Hb A(1c), creatinine, and blood urea nitrogen and urinary microalbumin excretion. The sEH-deficient diabetic mice also had decreased renal tubular apoptosis that coincided with increased levels of antiapoptotic Bcl-2 and Bcl-xl, and decreased levels of the proapoptotic Bax. These effects were associated with activation of the PI3K-Akt-NOS3 and AMPK signaling cascades. sEH gene inhibition and exogenous EETs significantly protected HK-2 cells from TNF alpha-induced apoptosis in vitro. These findings highlight the beneficial role of the CYP epoxygenase-EETs-sEH system in the pathogenesis of diabetic nephropathy and suggest that the sEH inhibitors available may be potential therapeutic agents for this condition.
C1 [Chen, Guangzhi; Xu, Renfan; Wang, Yinna; Wang, Peihua; Zhao, Gang; Xu, Xizhen; Wang, Dao Wen] Huazhong Univ Sci & Technol, Dept Internal Med, Tongji Hosp, Tongji Med Coll, Wuhan 430030, Peoples R China.
[Chen, Guangzhi; Xu, Renfan; Wang, Yinna; Wang, Peihua; Zhao, Gang; Xu, Xizhen; Wang, Dao Wen] Huazhong Univ Sci & Technol, Gene Therapy Ctr, Tongji Hosp, Tongji Med Coll, Wuhan 430030, Peoples R China.
[Gruzdev, Artiom; Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
RP Wang, DW (reprint author), Huazhong Univ Sci & Technol, Dept Internal Med, Tongji Hosp, Tongji Med Coll, 1095 Jiefang Ave, Wuhan 430030, Peoples R China.
EM dwwang@tjh.tjmu.edu.cn
FU National Basic Research Program (973) [2012CB517801]; NSFC [30930039,
30700377]; Wuhan City grant; National Institutes of Health, National
Institute of Environnmental Health Sciences [Z01 ES-025034]
FX This work was supported by National Basic Research Program (973) (no.
2012CB517801), NSFC grants (nos. 30930039, 30700377), a Wuhan City
grant, and the Intramural Research Program of the National Institutes of
Health, National Institute of Environnmental Health Sciences (Z01
ES-025034).
NR 54
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U1 2
U2 9
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1849
J9 AM J PHYSIOL-ENDOC M
JI Am. J. Physiol.-Endocrinol. Metab.
PD SEP
PY 2012
VL 303
IS 5
BP E563
EP E575
DI 10.1152/ajpendo.00591.2011
PG 13
WC Endocrinology & Metabolism; Physiology
SC Endocrinology & Metabolism; Physiology
GA 001MT
UT WOS:000308465500001
PM 22739108
ER
PT J
AU Brar, SS
Meyer, JN
Bortner, CD
Van Houten, B
Martin, WJ
AF Brar, Sukhdev S.
Meyer, Joel N.
Bortner, Carl D.
Van Houten, Bennett
Martin, William J., II
TI Mitochondrial DNA-depleted A549 cells are resistant to bleomycin
SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
LA English
DT Article
DE mitochondrial DNA damage; protein kinase D1; apoptosis; reactive oxygen
species; fibrosis
ID PROTEIN-KINASE-D; ACTIVATION LOOP SER(744); RHO-DEGREES CELLS; OXIDATIVE
STRESS; PROTEOLYTIC CLEAVAGE; REACTIVE OXYGEN; EXCISION-REPAIR;
LUNG-CELLS; C-MU; DAMAGE
AB Brar SS, Meyer JN, Bortner CD, Van Houten B, Martin WJ II. Mitochondrial DNA-depleted A549 cells are resistant to bleomycin. Am J Physiol Lung Cell Mol Physiol 303: L413-L424, 2012. First published July 6, 2012; doi:10.1152/ajplung.00343.2011.-Alveolar epithelial cells are considered to be the primary target of bleomycin-induced lung injury, leading to interstitial fibrosis. The molecular mechanisms by which bleomycin causes this damage are poorly understood but are suspected to involve generation of reactive oxygen species and DNA damage. We studied the effect of bleomycin on mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) in human alveolar epithelial A549 cells. Bleomycin caused an increase in reactive oxygen species production, DNA damage, and apoptosis in A549 cells; however, bleomycin induced more mtDNA than nDNA damage. DNA damage was associated with activation of caspase-3, cleavage of poly(ADPribose) polymerase, and cleavage and activation of protein kinase D1 (PKD1), a newly identified mitochondrial oxidative stress sensor. These effects appear to be mtDNA-dependent, because no caspase-3 or PKD1 activation was observed in mtDNA-depleted (rho(0)) A549 cells. Survival rate after bleomycin treatment was higher for A549 rho(0) than A549 cells. These results suggest that A549 rho(0) cells are more resistant to bleomycin toxicity than are parent A549 cells, likely in part due to the depletion of mtDNA and impairment of mitochondria-dependent apoptotic pathways.
C1 [Brar, Sukhdev S.; Martin, William J., II] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA.
[Meyer, Joel N.] Duke Univ, Nicholas Sch Environm, Durham, NC 27708 USA.
[Bortner, Carl D.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA.
[Van Houten, Bennett] Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Dept Pharmacol & Chem Biol, Pittsburgh, PA USA.
RP Martin, WJ (reprint author), NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, 31 Ctr Dr,Bldg 31,Rm 2A31, Bethesda, MD 20892 USA.
EM wjmartin@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Institute of Environmental Health Sciences
FX This research was supported in whole by the Intramural Research Program
of the National Institutes of Health, National Institute of
Environmental Health Sciences.
NR 50
TC 12
Z9 12
U1 1
U2 7
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1040-0605
J9 AM J PHYSIOL-LUNG C
JI Am. J. Physiol.-Lung Cell. Mol. Physiol.
PD SEP
PY 2012
VL 303
IS 5
BP L413
EP L424
DI 10.1152/ajplung.00343.2011
PG 12
WC Physiology; Respiratory System
SC Physiology; Respiratory System
GA 001MA
UT WOS:000308463600006
PM 22773697
ER
PT J
AU Warg, LA
Oakes, JL
Burton, R
Neidermyer, AJ
Rutledge, HR
Groshong, S
Schwartz, DA
Yang, IV
AF Warg, Laura A.
Oakes, Judy L.
Burton, Rachel
Neidermyer, Amanda J.
Rutledge, Holly R.
Groshong, Steve
Schwartz, David A.
Yang, Ivana V.
TI The role of the E2F1 transcription factor in the innate immune response
to systemic LPS
SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
LA English
DT Article
DE coagulation; gene expression; mRNA; miRNA
ID KAPPA-B; SEPSIS; INFLAMMATION; RECOGNITION; MACROPHAGES; DYSFUNCTION;
ACTIVATION; RECEPTORS; MICRORNAS
AB Warg LA, Oakes JL, Burton R, Neidermyer AJ, Rutledge HR, Groshong S, Schwartz DA, Yang IV. The role of the E2F1 transcription factor in the innate immune response to systemic LPS. Am J Physiol Lung Cell Mol Physiol 303: L391-L400, 2012. First published June 18, 2012; doi:10.1152/ajplung.00369.2011.-Previous publications from our and other groups identified E2F1 as a transcription factor involved in the regulation of inflammatory response to Toll-like receptor ligands including LPS. In this study, we challenged E2F1-deficient mice with LPS systemically and demonstrated decreased survival despite attenuated inflammatory response compared with controls. Gene expression profiling of liver tissue identified a dampened transcriptional response in the coagulation cascade in B6; 129(E2F1-/-) compared with B6x129 F2 mice. These data were further corroborated by increased prothrombin time, activated partial thromboplastin time, and fibrin split products in the blood of E2F1-deficient mice, suggesting disseminated intravascular coagulation as a consequence of uncontrolled sepsis providing at least a partial explanation for their decreased survival despite attenuated inflammatory response. To identify novel miRNAs involved in the innate immune response to LPS, we also performed miRNA profiling of liver tissue from B6; 129(E2F1-/-) and B6x129 F2 mice treated with LPS systemically. Our analysis identified a set of miRNAs and their mRNA targets that are significantly differentially regulated in E2F1-deficient but not control mice including let-7g, miR-101b, miR-181b, and miR-455. These miRNAs represent novel regulators of the innate immune response. In summary, we used transcriptional and miRNA profiling to characterize the response of E2F1-deficient mice to systemic LPS.
C1 [Neidermyer, Amanda J.; Groshong, Steve; Schwartz, David A.; Yang, Ivana V.] Univ Colorado Denver, Dept Med, Aurora, CO 80045 USA.
[Warg, Laura A.; Oakes, Judy L.; Burton, Rachel; Groshong, Steve; Schwartz, David A.; Yang, Ivana V.] Natl Jewish Hlth, Ctr Genes Environm & Hlth, Denver, CO USA.
[Rutledge, Holly R.] NIEHS, Res Triangle Pk, NC 27709 USA.
RP Yang, IV (reprint author), Univ Colorado Denver, Dept Med, 12700 E 19th Ave, Aurora, CO 80045 USA.
EM ivana.yang@ucdenver.edu
FU NIEHS NIH HHS [P01 ES018181]
NR 28
TC 8
Z9 8
U1 1
U2 6
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1040-0605
J9 AM J PHYSIOL-LUNG C
JI Am. J. Physiol.-Lung Cell. Mol. Physiol.
PD SEP
PY 2012
VL 303
IS 5
BP L391
EP L400
DI 10.1152/ajplung.00369.2011
PG 10
WC Physiology; Respiratory System
SC Physiology; Respiratory System
GA 001MA
UT WOS:000308463600004
PM 22707615
ER
PT J
AU Barak, S
Wang, ZF
Miettinen, M
AF Barak, Stephanie
Wang, Zengfeng
Miettinen, Markku
TI Immunoreactivity for Calretinin and Keratins in Desmoid Fibromatosis and
Other Myofibroblastic Tumors A Diagnostic Pitfall
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE calretinin; desmoid; nodular fasciitis; proliferative fasciitis;
myofibroblast; solitary fibrous tumor; immunohistochemistry; keratins
ID MALIGNANT MESOTHELIOMA; URINARY-BLADDER; EXPRESSION; CYTOKERATIN;
MARKERS; TISSUE; CELLS; GENE
AB Calretinin is an intracellular calcium-binding EF-hand protein of the calmodulin superfamily. It plays a role in diverse cellular functions, including message targeting and intracellular calcium signaling. It is expressed in the mesothelium, mast cells, some neural cells, and fat cells, among others. Because of its relative specificity for mesothelial neoplasms, calretinin is widely used as one of the primary immunohistochemical markers for malignant mesothelioma and in differentiating it from adenocarcinoma. On the basis of our sporadic observation on calretinin immunoreactivity in desmoid fibromatosis, we systematically evaluated calretinin, keratin cocktail (AE1/AE3), and WT1 immunoreactivity in 268 fibroblastic/myofibroblastic neoplasms. Calretinin was observed in 75% (44/58) of desmoid fibromatosis, 50% (21/42) of proliferative fasciitis, 23% (8/35) of nodular fasciitis, 33% (13/40) of benign fibrous histiocytoma, 35% (22/62) of malignant fibrous histiocytoma, and 13% (4/31) of solitary fibrous tumors but not in normal connective tissue fibroblasts at various sites. Keratin AE1/AE3 immunoreactivity was also commonly (6/13) present in the large ganglion-like cells of proliferative fasciitis and sometimes in nodular fasciitis (3/35), solitary fibrous tumor (3/27), and malignant fibrous histiocytoma (9/62). Nuclear immunoreactivity for WT1 or keratin 5 positivity was not detected in myofibroblastic tumors. On the basis of these observations, it can be concluded that calretinin and focal keratin immunoreactivity is fairly common in benign and malignant fibroblastic and myofibroblastic lesions. Calretinin-positive and keratin-positive spindle cells in desmoid and nodular fasciitis or calretinin-positive ganglion-like cells in proliferative fasciitis should not be confused with elements of epithelioid or sarcomatoid mesothelioma. These diagnostic pitfalls can be avoided with careful observation of morphology, quantitative differences in keratin expression, and use of additional immunohistochemical markers such keratin 5 and WT1 to verify true epithelial and mesothelial differentiation typical of mesothelioma.
C1 [Barak, Stephanie; Wang, Zengfeng; Miettinen, Markku] NCI, Pathol Lab, Bethesda, MD 20892 USA.
RP Miettinen, M (reprint author), NCI, Pathol Lab, 9000 Rockville Pike,Bldg 10,Rm 2B50, Bethesda, MD 20892 USA.
EM miettinenmm@mail.nih.gov
FU NCI's intramural research program
FX Supported as a part of NCI's intramural research program. The authors
have disclosed that they have no significant relationships with, or
financial interest in, any commercial companies pertaining to this
article.
NR 21
TC 12
Z9 13
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0147-5185
J9 AM J SURG PATHOL
JI Am. J. Surg. Pathol.
PD SEP
PY 2012
VL 36
IS 9
BP 1404
EP 1409
DI 10.1097/PAS.0b013e3182556def
PG 6
WC Pathology; Surgery
SC Pathology; Surgery
GA 998CF
UT WOS:000308214100015
PM 22531174
ER
PT J
AU Chuang, GY
Boyington, JC
Joyce, MG
Zhu, J
Nabel, GJ
Kwong, PD
Georgiev, I
AF Chuang, Gwo-Yu
Boyington, Jeffrey C.
Joyce, M. Gordon
Zhu, Jiang
Nabel, Gary J.
Kwong, Peter D.
Georgiev, Ivelin
TI Computational prediction of N-linked glycosylation incorporating
structural properties and patterns
SO BIOINFORMATICS
LA English
DT Article
ID RANDOM FORESTS; SITES; SEQUENCE; FEATURES; PROTEINS; SYSTEM
AB Motivation: N-linked glycosylation occurs predominantly at the N-X-T/S motif, where X is any amino acid except proline. Not all N-X-T/S sequons are glycosylated, and a number of web servers for predicting N-linked glycan occupancy using sequence and/or residue pattern information have been developed. None of the currently available servers, however, utilizes protein structural information for the prediction of N-glycan occupancy.
Results: Here, we describe a novel classifier algorithm, NGlycPred, for the prediction of glycan occupancy at the N-X-T/S sequons. The algorithm utilizes both structural as well as residue pattern information and was trained on a set of glycosylated protein structures using the Random Forest algorithm. The best predictor achieved a balanced accuracy of 0.687 under 10-fold cross-validation on a curated dataset of 479 N-X-T/S sequons and outperformed sequence-based predictors when evaluated on the same dataset. The incorporation of structural information, including local contact order, surface accessibility/composition and secondary structure thus improves the prediction accuracy of glycan occupancy at the N-X-T/S consensus sequon.
C1 [Chuang, Gwo-Yu; Boyington, Jeffrey C.; Joyce, M. Gordon; Zhu, Jiang; Nabel, Gary J.; Kwong, Peter D.; Georgiev, Ivelin] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Georgiev, I (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
FU Intramural Research Program (National Institute of Allergy and
Infectious Diseases, NIH, USA)
FX Intramural Research Program (National Institute of Allergy and
Infectious Diseases, NIH, USA).
NR 27
TC 20
Z9 21
U1 3
U2 18
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
J9 BIOINFORMATICS
JI Bioinformatics
PD SEP 1
PY 2012
VL 28
IS 17
BP 2249
EP 2255
DI 10.1093/bioinformatics/bts426
PG 7
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA 995OL
UT WOS:000308019200005
PM 22782545
ER
PT J
AU Razzaghi, H
Troester, MA
Gierach, GL
Olshan, AF
Yankaskas, BC
Millikan, RC
AF Razzaghi, Hilda
Troester, Melissa A.
Gierach, Gretchen L.
Olshan, Andrew F.
Yankaskas, Bonnie C.
Millikan, Robert C.
TI Mammographic density and breast cancer risk in White and African
American Women
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Mammographic breast density; Breast cancer; Race; African American;
Epidemiology
ID POSTMENOPAUSAL HORMONE-THERAPY; PARENCHYMAL PATTERNS; REPLACEMENT
THERAPY; MULTIETHNIC COHORT; RECORD LINKAGE; UNITED-STATES; AGE; RACE;
CLASSIFICATION; EPIDEMIOLOGY
AB Mammographic density is a strong risk factor for breast cancer, but limited data are available in African American (AA) women. We examined the association between mammographic density and breast cancer risk in AA and white women. Cases (n = 491) and controls (n = 528) were from the Carolina Breast Cancer Study (CBCS) who also had mammograms recorded in the Carolina Mammography Registry (CMR). Mammographic density was reported to CMR using Breast Imaging Reporting and Data System (BI-RADS) categories. Increasing mammographic density was associated with increased breast cancer risk among all women. After adjusting for potential confounders, a monotonically increasing risk of breast cancer was observed between the highest versus the lowest BI-RADS density categories [OR = 2.45, (95 % confidence interval: 0.99, 6.09)]. The association was stronger in whites, with similar to 40 % higher risk among those with extremely dense breasts compared to those with scattered fibroglandular densities [1.39, (0.75, 2.55)]. In AA women, the same comparison suggested lower risk [0.75, (0.30, 1.91)]. Because age, obesity, and exogenous hormones have strong associations with breast cancer risk, mammographic density, and race in the CBCS, effect measure modification by these factors was considered. Consistent with previous literature, density-associated risk was greatest among those with BMI > 30 and current hormone users (P value = 0.02 and 0.01, respectively). In the CBCS, mammographic density is associated with increased breast cancer risk, with some suggestion of effect measure modification by race, although results were not statistically significant. However, exposures such as BMI and hormone therapy may be important modifiers of this association and merit further investigation.
C1 [Razzaghi, Hilda; Troester, Melissa A.; Olshan, Andrew F.; Millikan, Robert C.] Univ N Carolina, Gillings Global Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[Troester, Melissa A.; Olshan, Andrew F.; Millikan, Robert C.] Univ N Carolina, Linberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Gierach, Gretchen L.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
[Yankaskas, Bonnie C.] Univ N Carolina, Sch Med, Dept Radiol, Chapel Hill, NC 27516 USA.
RP Razzaghi, H (reprint author), Univ N Carolina, Gillings Global Sch Publ Hlth, Dept Epidemiol, 2104 McGavran Greenberg,135 Dauer Dr,Campus Box 7, Chapel Hill, NC 27599 USA.
EM hildar@unc.edu; troester@email.unc.edu; gierachg@mail.nih.gov;
Andy_olshan@unc.edu; bcy@med.unc.edu; millikan@email.unc.edu
RI Gierach, Gretchen/E-1817-2016
OI Gierach, Gretchen/0000-0002-0165-5522
FU NIH; National Cancer Institute; National Institutes for Environmental
Health Sciences and National Cancer Institute Breast Cancer; Environment
Research Program [5U01ES019472-02]; NCI [5R01CA138255]; SPORE in Breast
Cancer [5P50CA058233]
FX The authors are grateful to Jessica Tse and Robert Christopher Allis for
their assistance with data management and data analysis for this
manuscript. This research was supported [in part] by the Intramural
Research Program of the NIH and the National Cancer Institute. M. A. T
was supported by the National Institutes for Environmental Health
Sciences and National Cancer Institute Breast Cancer and the Environment
Research Program 5U01ES019472-02 and NCI grant 5R01CA138255. R. C. M.
and M. A. T are supported by a SPORE in Breast Cancer 5P50CA058233.
NR 52
TC 19
Z9 19
U1 0
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD SEP
PY 2012
VL 135
IS 2
BP 571
EP 580
DI 10.1007/s10549-012-2185-3
PG 10
WC Oncology
SC Oncology
GA 996QU
UT WOS:000308108700022
PM 22864770
ER
PT J
AU Senadheera, S
Kim, Y
Grayson, TH
Toemoe, S
Kochukov, MY
Abramowitz, J
Housley, GD
Bertrand, RL
Chadha, PS
Bertrand, PP
Murphy, TV
Tare, M
Birnbaumer, L
Marrelli, SP
Sandow, SL
AF Senadheera, Sevvandi
Kim, Youngsoo
Grayson, T. Hilton
Toemoe, Sianne
Kochukov, Mikhail Y.
Abramowitz, Joel
Housley, Gary D.
Bertrand, Rebecca L.
Chadha, Preet S.
Bertrand, Paul P.
Murphy, Timothy V.
Tare, Marianne
Birnbaumer, Lutz
Marrelli, Sean P.
Sandow, Shaun L.
TI Transient receptor potential canonical type 3 channels facilitate
endothelium-derived hyperpolarization-mediated resistance artery
vasodilator activity
SO CARDIOVASCULAR RESEARCH
LA English
DT Article
DE Endothelium; Calcium channel; Potassium channel; Signalling microdomain;
Smooth muscle; Vasodilation
ID MYOENDOTHELIAL GAP-JUNCTIONS; RAT MESENTERIC-ARTERY; ACTIVATED POTASSIUM
CHANNELS; SMOOTH-MUSCLE-CELLS; INOSITOL 1,4,5-TRISPHOSPHATE; TRPC3
CHANNELS; SHEAR-STRESS; K+ CHANNELS; CA2+; CALCIUM
AB Microdomain signalling mechanisms underlie key aspects of artery function and the modulation of intracellular calcium, with transient receptor potential (TRP) channels playing an integral role. This study determines the distribution and role of TRP canonical type 3 (C3) channels in the control of endothelium-derived hyperpolarization (EDH)-mediated vasodilator tone in rat mesenteric artery.
TRPC3 antibody specificity was verified using rat tissue, human embryonic kidney (HEK)-293 cells stably transfected with mouse TRPC3 cDNA, and TRPC3 knock-out (KO) mouse tissue using western blotting and confocal and ultrastructural immunohistochemistry. TRPC3-Pyr3 (ethyl-1-(4-(2,3,3-trichloroacrylamide)phenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate) specificity was verified using patch clamp of mouse mesenteric artery endothelial and TRPC3-transfected HEK cells, and TRPC3 KO and wild-type mouse aortic endothelial cell calcium imaging and mesenteric artery pressure myography. TRPC3 distribution, expression, and role in EDH-mediated function were examined in rat mesenteric artery using immunohistochemistry and western blotting, and pressure myography and endothelial cell membrane potential recordings. In rat mesenteric artery, TRPC3 was diffusely distributed in the endothelium, with approximately five-fold higher expression at potential myoendothelial microdomain contact sites, and immunoelectron microscopy confirmed TRPC3 at these sites. Western blotting and endothelial damage confirmed primary endothelial TRPC3 expression. In rat mesenteric artery endothelial cells, Pyr3 inhibited hyperpolarization generation, and with individual SKCa (apamin) or IKCa (TRAM-34) block, Pyr3 abolished the residual respective IKCa- and SKCa-dependent EDH-mediated vasodilation.
The spatial localization of TRPC3 and associated channels, receptors, and calcium stores are integral for myoendothelial microdomain function. TRPC3 facilitates endothelial SKCa and IKCa activation, as key components of EDH-mediated vasodilator activity and for regulating mesenteric artery tone.
C1 [Senadheera, Sevvandi; Kim, Youngsoo; Grayson, T. Hilton; Toemoe, Sianne; Housley, Gary D.; Bertrand, Rebecca L.; Chadha, Preet S.; Bertrand, Paul P.; Murphy, Timothy V.; Sandow, Shaun L.] Univ New S Wales, Fac Med, Sch Med Sci, Dept Physiol, Sydney, NSW 2052, Australia.
[Kochukov, Mikhail Y.; Marrelli, Sean P.] Baylor Coll Med, Dept Anesthesiol, Houston, TX 77030 USA.
[Abramowitz, Joel; Birnbaumer, Lutz] Natl Inst Environm Hlth Sci, Transmembrane Signalling Grp, Neurobiol Lab, NIH, Res Triangle Pk, NC USA.
[Chadha, Preet S.] Univ London, Div Biomed Sci, London SW17 0RE, England.
[Tare, Marianne] Monash Univ, Dept Physiol, Melbourne, Vic 3800, Australia.
[Marrelli, Sean P.] Baylor Coll Med, Dept Physiol & Biophys, Houston, TX 77030 USA.
[Marrelli, Sean P.] Baylor Coll Med, Grad Program Physiol Cardiovasc Sci, Houston, TX 77030 USA.
RP Senadheera, S (reprint author), Univ New S Wales, Fac Med, Sch Med Sci, Dept Physiol, Sydney, NSW 2052, Australia.
EM s.senadheera@student.unsw.edu.au; shaun.sandow@unsw.edu.au
RI Grayson, Thomas/F-2708-2011; Abramowitz, Joel/A-2620-2015; Sandow,
Shaun/N-4256-2016;
OI Sandow, Shaun/0000-0002-0753-2742; Bertrand, Paul/0000-0003-1122-2306;
Housley, Gary/0000-0002-8413-588X
FU National Health and Medical Research Council of Australia [ID401112,
455243, 510202, 546087]; Australian Research Council [DP1097202];
National Institutes of Health [Z01-ES-101684, R01 HL088435]
FX This work was supported by grants from the National Health and Medical
Research Council of Australia (ID401112 and 455243 to S. L. S., 510202
to P. B., and 546087 to M. T. and S. L. S.), the Australian Research
Council (DP1097202 to G. D. H.), and the National Institutes of Health
(project Z01-ES-101684 to L. B. and R01 HL088435 to S.P.M.).
NR 55
TC 36
Z9 37
U1 0
U2 16
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0008-6363
J9 CARDIOVASC RES
JI Cardiovasc. Res.
PD SEP 1
PY 2012
VL 95
IS 4
BP 439
EP 447
DI 10.1093/cvr/cvs208
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 992MV
UT WOS:000307781800009
PM 22721989
ER
PT J
AU Norris, KC
Agodoa, LY
AF Norris, Keith C.
Agodoa, Lawrence Y.
TI Reducing Disparities in Assessment for Kidney Transplantation
SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Editorial Material
ID STAGE RENAL-DISEASE; UNITED-STATES; NEIGHBORHOOD POVERTY; RACIAL
DISPARITIES; ACCESS; DIALYSIS
C1 [Norris, Keith C.] Charles Drew Univ, Dept Med, Los Angeles, CA USA.
[Norris, Keith C.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Agodoa, Lawrence Y.] NIDDKD, NIH, Bethesda, MD 20892 USA.
RP Norris, KC (reprint author), Charles Drew Univ Med & Sci, 11705 Deputy Yamamoto Pl,Suite B, Lynwood, CA 90262 USA.
EM keithnorris@cdrewu.edu
FU NCATS NIH HHS [UL1 TR000124]; NCRR NIH HHS [UL1 RR033176, UL1RR033176];
NIA NIH HHS [P30 AG021684, P30AG021684]; NIMHD NIH HHS [U54 MD007598,
P20 MD000182, U54MD007598, P20-MD000182]
NR 16
TC 2
Z9 2
U1 1
U2 1
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1555-9041
J9 CLIN J AM SOC NEPHRO
JI Clin. J. Am. Soc. Nephrol.
PD SEP
PY 2012
VL 7
IS 9
BP 1378
EP 1381
DI 10.2215/CJN.07690712
PG 4
WC Urology & Nephrology
SC Urology & Nephrology
GA 002DG
UT WOS:000308510600002
PM 22904121
ER
PT J
AU Hall, KD
AF Hall, Kevin D.
TI Metabolism of mice and men: mathematical modeling of body weight
dynamics
SO CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE
LA English
DT Review
DE body weight regulation; energy balance; mathematical model
ID ENERGY-INTAKE; COMPUTATIONAL MODEL; OBESITY; BALANCE; CALORIE;
PERSPECTIVE; ADAPTATION; OUTCOMES; HUMANS; LEPTIN
AB Purpose of review
Dynamic interrelationships between food intake, energy expenditure, energy partitioning, and metabolic fuel selection underlie changes in body weight and composition. A quantitative understanding of these interrelationships is becoming increasingly important given the rise of the worldwide obesity epidemic and the widespread interest in weight management. This review describes how mathematical models offer a quantitative framework for integrating dynamic physiological and behavioral data underlying body weight dynamics in both humans and mice.
Recent findings
Mathematical models have provided important insights regarding the drivers of the obesity epidemic, how metabolism adapts to different diets, the predicted magnitude and variability of weight change, and why mouse models have obesity phenotypes. Because mathematical models are constrained by conservation laws, they can also be used to infer physiological variables that are difficult to measure directly.
Summary
Mathematical models can help improve our understanding of the dynamic energy and macronutrient imbalances that give rise to changes in body weight and composition over time. The model development process can also highlight important knowledge gaps and model simulations can help design and predict the results of key new experiments to fill those gaps.
C1 [Hall, Kevin D.] NIDDKD, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
RP Hall, KD (reprint author), 12A South Dr,Room 4007, Bethesda, MD 20892 USA.
EM kevinh@niddk.nih.gov
FU Intramural Research Program of the NIH, National Institute of Diabetes &
Digestive & Kidney Diseases
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Diabetes & Digestive & Kidney Diseases.
NR 39
TC 3
Z9 3
U1 2
U2 13
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1363-1950
J9 CURR OPIN CLIN NUTR
JI Curr. Opin. Clin. Nutr. Metab. Care
PD SEP
PY 2012
VL 15
IS 5
BP 418
EP 423
DI 10.1097/MCO.0b013e3283561150
PG 6
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 993AW
UT WOS:000307826500003
PM 22878236
ER
PT J
AU Song, JY
Filie, AC
Venzon, D
Stetler-Stevenson, M
Yuan, CM
AF Song, Joo Y.
Filie, Armando C.
Venzon, David
Stetler-Stevenson, Maryalice
Yuan, Constance M.
TI Evaluation of flow cytometric assessment of myeloid nuclear
differentiation antigen expression as a diagnostic marker for
myelodysplastic syndromes in a series of 269 patients
SO CYTOMETRY PART B-CLINICAL CYTOMETRY
LA English
DT Article
DE myeloid nuclear differentiation antigen (MNDA); myelodysplastic syndrome
(MDS); flow cytometry; leukemia
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; IN-SITU HYBRIDIZATION; NORMAL BONE-MARROW;
SCORING SYSTEM; CHROMOSOMAL-ABNORMALITIES; QUANTITATIVE ASSESSMENT;
PROGNOSTIC-SIGNIFICANCE; WORKING CONFERENCE; COOPERATIVE GROUP;
GENE-EXPRESSION
AB Background: Myeloid nuclear differentiation antigen (MNDA) is expressed in myelomonocytic cells with highest levels in mature granulocytes and monocytes. It is suggested to be expressed more weakly in patients with myelodysplastic syndromes (MDS). The analysis of MNDA therefore may improve diagnostic capabilities of multiparameter flow cytometry (MFC) in MDS. Methods: We used MFC for detection of MNDA expression in 269 patients with suspected or known MDS, acute myeloid leukemia (AML) or chronic myelomonocytic leukemia (CMML), cytopenia of unknown cause or without malignancy (negative controls). Results were compared with the diagnoses revealed by cytomorphology (CM) and cytogenetics (CG). Results: Percentages of granulocytes and monocytes with diminished MNDA expression (dimG and dimM) were higher in patients with MDS (mean +/- SD, 20% +/- 20%, P < 0.001 and 31% +/- 24%, P < 0.001) and AML (27% +/- 27%, P = 0.007 and 45% +/- 31%, P = 0.001) diagnosed by CM, vs. patients without MDS (8% +/- 10% and 16% +/- 11%), respectively. Significant differences were also found for mean fluorescence intensity (MFI) of MNDA in monocytes which was lower in MDS (mean +/- SD, 71 +/- 36, P = 0.004) and AML (55 +/- 39, P < 0.001) vs. no MDS samples (85 +/- 28), respectively. Within patients with MDS, cases with cytogenetic aberrations showed a trend to higher %dimG (24% +/- 18%, P = 0.083) compared with those without (16% +/- 21%). Cut-off values for %dimG (12%) and %dimM (22%) as well as for MFI in monocytes (72) were defined capable of discriminating between MDS and non-MDS. Conclusion: MNDA expression in bone marrow cells can be assessed reliably by MFC and may facilitate evaluation of dyspoiesis when added to a standard MDS MFC panel. (c) 2012 International Clinical Cytometry Society
C1 [Yuan, Constance M.] NCI, Flow Cytometry Div, Pathol Lab, Ctr Canc Res,Hematopathol Sect,NIH, Bethesda, MD 20892 USA.
[Filie, Armando C.] NCI, Cytopathol Sect, NIH, Bethesda, MD 20892 USA.
[Venzon, David] NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA.
RP Yuan, CM (reprint author), NCI, Flow Cytometry Div, Pathol Lab, Ctr Canc Res,Hematopathol Sect,NIH, Bldg 10,Room 2N108,10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA.
EM yuanc@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 45
TC 3
Z9 3
U1 2
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4949
J9 CYTOM PART B-CLIN CY
JI Cytom. Part B-Clin. Cytom.
PD SEP
PY 2012
VL 82B
IS 5
BP 305
EP 312
DI 10.1002/cyto.b.21026
PG 8
WC Medical Laboratory Technology; Pathology
SC Medical Laboratory Technology; Pathology
GA 001MU
UT WOS:000308465600008
PM 22837143
ER
PT J
AU Santiago, MI
Stetler-Stevenson, M
Yuan, C
Ramesh, P
AF Santiago, Margo I.
Stetler-Stevenson, Maryalice
Yuan, Constance
Ramesh, Prashant
TI THE EFFECT OF DIFFERENT ANTICOAGULANTS ON SPECIMEN STABILITY AND
LEUKOCYTE SUBSETS
SO CYTOMETRY PART B-CLINICAL CYTOMETRY
LA English
DT Meeting Abstract
CT 27th Annual Meeting of the International-Clinical-Cytometry-Society
CY OCT 05-09, 2012
CL New Orleans, LA
SP Int Clin Cytometry Soc
C1 [Santiago, Margo I.; Stetler-Stevenson, Maryalice; Yuan, Constance; Ramesh, Prashant] NCI, Bethesda, MD 20892 USA.
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 1552-4949
J9 CYTOM PART B-CLIN CY
JI Cytom. Part B-Clin. Cytom.
PD SEP
PY 2012
VL 82B
IS 5
MA P35
BP 339
EP 339
PG 1
WC Medical Laboratory Technology; Pathology
SC Medical Laboratory Technology; Pathology
GA 001MU
UT WOS:000308465600046
ER
PT J
AU Tembhare, PR
Marti, G
Wiestner, A
Degheidy, H
Farooqui, M
Kreitman, RJ
Jasper, GA
Yuan, CM
Liewehr, D
Venzon, D
Stetler-Stevenson, M
AF Tembhare, Prashant R.
Marti, Gerald
Wiestner, Adrian
Degheidy, Heba
Farooqui, Mohammed
Kreitman, Robert J.
Jasper, Gregory A.
Yuan, Constance M.
Liewehr, David
Venzon, David
Stetler-Stevenson, Maryalice
TI QUANTIFICATION OF EXPRESSION OF ANTIGENS TARGETED BY ANTIBODY BASED
THERAPY IN CHRONIC LYMPHOCYTIC LEUKEMIA
SO CYTOMETRY PART B-CLINICAL CYTOMETRY
LA English
DT Meeting Abstract
CT 27th Annual Meeting of the International-Clinical-Cytometry-Society
CY OCT 05-09, 2012
CL New Orleans, LA
SP Int Clin Cytometry Soc
C1 [Tembhare, Prashant R.; Jasper, Gregory A.; Yuan, Constance M.; Stetler-Stevenson, Maryalice] NCI, Flow Cytometry Unit, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Marti, Gerald; Degheidy, Heba] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA.
[Wiestner, Adrian; Farooqui, Mohammed] NHLBI, NIH, Bethesda, MD USA.
[Kreitman, Robert J.] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Liewehr, David; Venzon, David] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4949
J9 CYTOM PART B-CLIN CY
JI Cytom. Part B-Clin. Cytom.
PD SEP
PY 2012
VL 82B
IS 5
MA P39
BP 340
EP 340
PG 1
WC Medical Laboratory Technology; Pathology
SC Medical Laboratory Technology; Pathology
GA 001MU
UT WOS:000308465600050
ER
PT J
AU Larochelle, A
AF Larochelle, Andre
TI Cord blood culture in hypoxia: making the cells feel at home
SO CYTOTHERAPY
LA English
DT Editorial Material
ID STEM-CELL; EMBRYONIC-DEVELOPMENT; OXYGEN
C1 NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA.
RP Larochelle, A (reprint author), NHLBI, NIH, Hematol Branch, Bldg 10, Bethesda, MD 20892 USA.
EM larochea@nhlbi.nih.gov
NR 13
TC 0
Z9 0
U1 0
U2 3
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 2012
VL 14
IS 8
BP 900
EP 901
DI 10.3109/14653249.2012.721923
PG 2
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology; Hematology; Medicine, Research & Experimental
SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research
& Experimental Medicine
GA 995ID
UT WOS:000308000600001
PM 22928589
ER
PT J
AU Mamidi, MK
Pal, R
Dey, S
Bin Abdullah, BJJ
Zakaria, Z
Rao, MS
Das, AK
AF Mamidi, Murali Krishna
Pal, Rajarshi
Dey, Sovan
Bin Abdullah, Basri Johan Jeet
Zakaria, Zubaidah
Rao, Mahendra S.
Das, Anjan Kumar
TI Cell therapy in critical limb ischemia: current developments and future
progress
SO CYTOTHERAPY
LA English
DT Review
DE angiogenesis; animal studies; cell replacement therapy; clinical trials;
critical limb ischemia; peripheral artery disease; stem cells
ID EMBRYONIC STEM-CELLS; ENDOTHELIAL PROGENITOR CELLS; PERIPHERAL
ARTERIAL-DISEASE; MARROW MONONUCLEAR-CELLS; MICROPARTICLES INDUCE
ANGIOGENESIS; SMOOTH-MUSCLE-CELLS; IN-VIVO; POSTNATAL
NEOVASCULARIZATION; BLOOD-VESSELS; POSTISCHEMIC REVASCULARIZATION
AB Critical limb ischemia (CLI) is a syndrome manifested by ischemic rest pain, non-healing ulcers and tissue loss. CLI patients are at very high risk of amputation and experience poor physical function, leading to severe morbidity and mortality. The fundamental goal for CLI treatment is to relieve ischemic rest pain, heal ulcers, prevent limb loss and improve the quality of life, thereby extending the survival of the patient. Surgical or endovascular revascularization aimed at increasing blood flow is currently available for limb salvage in CLI. However, up to 30% of CLI patients are not suitable for such interventions because of high operative risk or unfavorable vascular anatomy. Therefore exploring new and more effective strategies for revascularization of ischemic limbs is imperative for the establishment of a viable therapeutic alternative. With the emergence of new approaches, this review describes up-to-date progress and developments in cell-based therapy as a novel and promising alternative for CLI treatment. Preliminary clinical data have established the safety, feasibility and efficacy of stem cells, and numerous studies are underway to consolidate this evidence further. However, significant hurdles remain to be addressed before this research can be responsibly translated to the bedside. In particular, we need better understanding of the behavior of cells post-transplantation and to learn how to control their survival and migration proliferation/differentiation in the hostile pathologic environment. Future research should focus on methods of isolation, optimal dosage, appropriate cell type, route of administration, role of tissue-derived factors and supportive endogenous stimulation.
C1 [Mamidi, Murali Krishna; Das, Anjan Kumar] Stempeut Res Malaysia Sdn Bhd, Kuala Lumpur 57000, Malaysia.
[Mamidi, Murali Krishna; Pal, Rajarshi] Manipal Univ, Manipal Inst Regenerat Med, Bangalore, Karnataka, India.
[Dey, Sovan] La Trobe Univ, Sch Publ Hlth, Bundoora, Vic 3086, Australia.
[Bin Abdullah, Basri Johan Jeet] Univ Malaya, Dept Biomed Imaging, Kuala Lumpur, Malaysia.
[Zakaria, Zubaidah] Inst Med Res, Hematol Unit, Kuala Lumpur 50588, Malaysia.
[Rao, Mahendra S.] NIH, Ctr Regenerat Med, Bethesda, MD 20892 USA.
RP Das, AK (reprint author), Stempeut Res Malaysia Sdn Bhd, Technol Pk Malaysia, Kuala Lumpur 57000, Malaysia.
EM anjan.das@stempeutics.com.my
FU Stempeutics Research Malaysia
FX The authors are grateful to Stempeutics Research Malaysia for the
funding to carry out research on stem cells and regenerative medicine.
We also acknowledge the scientific staff of Stempeutics for their
support, which helped to improve the manuscript. The authors acknowledge
Megan Laycock for careful proofreading of the manuscript.
NR 118
TC 15
Z9 16
U1 0
U2 7
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 2012
VL 14
IS 8
BP 902
EP 916
DI 10.3109/14653249.2012.693156
PG 15
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology; Hematology; Medicine, Research & Experimental
SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research
& Experimental Medicine
GA 995ID
UT WOS:000308000600002
PM 22731756
ER
PT J
AU Seitz, AE
Prevots, DR
Holland, SM
AF Seitz, Amy E.
Prevots, D. Rebecca
Holland, Steven M.
TI Hospitalizations Associated with Disseminated Coccidioidomycosis,
Arizona and California, USA
SO EMERGING INFECTIOUS DISEASES
LA English
DT Article
ID OUTBREAK; DISEASE
AB We analyzed hospitalization databases from Arizona and California for disseminated coccidioidomycosis associated hospitalizations among immunocompetent persons. Racial/ethnic disease ratios were characterized by a higher incidence of hospitalization among blacks compared with other groups. This finding suggests that HIV infection, AIDS, and primary immune conditions are not a major factor in this disparity.
C1 [Seitz, Amy E.; Prevots, D. Rebecca; Holland, Steven M.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Seitz, AE (reprint author), NIAID, NIH, 9000 Rockville Pike,Bldg 15B-1, Bethesda, MD 20892 USA.
EM seitza@niaid.nih.gov
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases.
NR 12
TC 6
Z9 6
U1 1
U2 6
PU CENTERS DISEASE CONTROL
PI ATLANTA
PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA
SN 1080-6040
J9 EMERG INFECT DIS
JI Emerg. Infect. Dis
PD SEP
PY 2012
VL 18
IS 9
BP 1476
EP 1479
DI 10.3201/eid1809.120151
PG 4
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 995EC
UT WOS:000307989700013
PM 22931562
ER
PT J
AU Chen, M
Berger, A
Kablan, A
Zhang, JD
Gavrilova, O
Weinstein, LS
AF Chen, Min
Berger, Alta
Kablan, Ahmed
Zhang, Jiandi
Gavrilova, Oksana
Weinstein, Lee S.
TI G(s)alpha Deficiency in the Paraventricular Nucleus of the Hypothalamus
Partially Contributes to Obesity Associated with G(s)alpha Mutations
SO ENDOCRINOLOGY
LA English
DT Article
ID CENTRAL MELANOCORTIN SYSTEM; CENTRAL-NERVOUS-SYSTEM;
PSEUDOHYPOPARATHYROIDISM TYPE 1A; LIPID-METABOLISM; FOOD-INTAKE;
RECEPTOR; GENE; MICE; KNOCKOUT; THERMOGENESIS
AB The G protein alpha-subunit G(s)alpha mediates receptor-stimulated cAMP generation. Heterozygous inactivating G(s)alpha mutations on the maternal allele result in obesity primarily due to reduced energy expenditure in Albright hereditary osteodystrophy patients and in mice. We previously showed that mice with central nervous system (CNS)-specific G(s)alpha deletion on the maternal allele (mBrGs KO) also develop severe obesity with reduced energy expenditure and that G(s)alpha is primarily expressed from the maternal allele in the paraventricular nucleus (PVN) of the hypothalamus, an important site of energy balance regulation. We now generated mice with PVN-specific G(s)alpha deficiency by mating Single-minded 1-cre and G(s)alpha-floxed mice. Homozygous G(s)alpha deletion produced early lethality. Heterozygotes with maternal G(s)alpha deletion (mPVNGsKO) also developed obesity and had small reductions in energy expenditure. However, this effect was much milder than that found in mBrGsKO mice and was more prominent in males. We previously showed mBrGsKO mice to have significant reductions in melanocortin receptor agonist-stimulated energy expenditure and now show that mBrGsKO mice have impaired cold-induced brown adipose tissue stimulation. In contrast, these effects were absent in mPVNGsKO mice. mPVNGsKO mice also had minimal effects on glucose metabolism as compared with mBrGsKO mice. Consistent with the presence of G(s)alpha imprinting, paternal heterozygotes showed no changes in energy or glucose metabolism. These results indicate that although G(s)alpha deficiency in PVN partially contributes to the metabolic phenotype resulting from maternal G(s)alpha mutations, G(s)alpha imprinting in other CNS regions is also important in mediating the CNS effects of G(s)alpha mutations on energy and glucose metabolism. (Endocrinology 153: 4256-4265, 2012)
C1 [Chen, Min; Berger, Alta; Zhang, Jiandi; Weinstein, Lee S.] NIDDKD, Signal Transduct Sect, Metab Dis Branch, NIH, Bethesda, MD 20892 USA.
[Gavrilova, Oksana] NIDDKD, Mouse Metab Core Lab, NIH, Bethesda, MD 20892 USA.
RP Chen, M (reprint author), NIDDKD, Signal Transduct Sect, Metab Dis Branch, NIH, Bldg 10,Room 8C101, Bethesda, MD 20892 USA.
EM minc@niddk.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health, Bethesda, MD
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health, Bethesda, MD.
NR 36
TC 16
Z9 16
U1 2
U2 8
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 2012
VL 153
IS 9
BP 4256
EP 4265
DI 10.1210/en.2012-1113
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 997VH
UT WOS:000308194900016
PM 22733970
ER
PT J
AU Bashour, NM
Wray, S
AF Bashour, Nicholas Michael
Wray, Susan
TI Progesterone Directly and Rapidly Inhibits GnRH Neuronal Activity via
Progesterone Receptor Membrane Component 1
SO ENDOCRINOLOGY
LA English
DT Article
ID GONADOTROPIN-RELEASING-HORMONE; FOLLICLE-STIMULATING-HORMONE;
IMMORTALIZED GRANULOSA-CELLS; EMBRYONIC OLFACTORY PLACODE;
NUCLEOTIDE-GATED CHANNELS; POLYCYSTIC-OVARY-SYNDROME; MESSENGER-RNA
STABILITY; G-DEPENDENT MECHANISM; LUTEINIZING-HORMONE; RHESUS-MONKEY
AB GnRH neurons are essential for reproduction, being an integral component of the hypothalamic-pituitary-gonadal axis. Progesterone (P4), a steroid hormone, modulates reproductive behavior and is associated with rapid changes in GnRH secretion. However, a direct action of P4 on GnRH neurons has not been previously described. Receptors in the progestin/adipoQ receptor family (PAQR), as well as progesterone receptor membrane component 1 (PgRMC1) and its partner serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1) mRNA binding protein 1 (SERBP1), have been shown to mediate rapid progestin actions in various tissues, including the brain. This study shows that PgRMC1 and SERBP1, but not PAQR, are expressed in prenatal GnRH neurons. Expression of PgRMC1 and SERBP1 was verified in adult mouse GnRH neurons. To investigate the effect of P4 on GnRH neuronal activity, calcium imaging was used on primary GnRH neurons maintained in explants. Application of P4 significantly decreased the activity of GnRH neurons, independent of secretion of gamma-aminobutyric acidergic and glutamatergic input, suggesting a direct action of P4 on GnRH neurons. Inhibition was not blocked by RU486, an antagonist of the classic nuclear P4 receptor. Inhibition was also maintained after uncoupling of the inhibitory regulative G protein (G(i/o)), the signal transduction pathway used by PAQR. However, AG-205, a PgRMC1 ligand and inhibitor, blocked the rapid P4-mediated inhibition, and inhibition of protein kinase G, thought to be activated downstream of PgRMC1, also blocked the inhibitory activity of P4. These data show for the first time that P4 can act directly on GnRH neurons through PgRMC1 to inhibit neuronal activity. (Endocrinology 153: 4457-4469, 2012)
C1 [Bashour, Nicholas Michael; Wray, Susan] NINDS, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
RP Wray, S (reprint author), NINDS, Cellular & Dev Neurobiol Sect, NIH, 35 Lincoln Dr,Bldg 35,Room 3A-1010, Bethesda, MD 20892 USA.
EM wrays@mail.nih.gov
OI wray, susan/0000-0001-7670-3915
FU Intramural Research Program of the National Institute of Neurological
Disorders and Stroke, National Institutes of Health [ZIA NS002824-21]
FX This work was supported by the Intramural Research Program of the
National Institute of Neurological Disorders and Stroke, National
Institutes of Health (ZIA NS002824-21).
NR 87
TC 28
Z9 29
U1 0
U2 10
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
EI 1945-7170
J9 ENDOCRINOLOGY
JI Endocrinology
PD SEP
PY 2012
VL 153
IS 9
BP 4457
EP 4469
DI 10.1210/en.2012-1122
PG 13
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 997VH
UT WOS:000308194900034
PM 22822163
ER
PT J
AU Cote, ML
Liu, M
Bonassi, S
Neri, M
Schwartz, AG
Christiani, DC
Spitz, MR
Muscat, JE
Rennert, G
Aben, KK
Andrew, AS
Bencko, V
Bickeboller, H
Boffetta, P
Brennan, P
Brenner, H
Duell, EJ
Fabianova, E
Field, JK
Foretova, L
Friis, S
Harris, CC
Holcatova, I
Hong, YC
Isla, D
Janout, V
Kiemeney, LA
Kiyohara, C
Lan, Q
Lazarus, P
Lissowska, J
Le Marchand, L
Mates, D
Matsuo, K
Mayordomo, JI
McLaughlin, JR
Morgenstern, H
Mueller, H
Orlow, I
Park, BJ
Pinchev, M
Raji, OY
Rennert, HS
Rudnai, P
Seow, A
Stucker, I
Szeszenia-Dabrowska, N
Teare, MD
Tjonnelan, A
Ugolini, D
van der Heijden, HFM
Wichmann, E
Wiencke, JK
Woll, PJ
Yang, P
Zaridze, D
Zhang, ZF
Etzel, CJ
Hung, RJ
AF Cote, Michele L.
Liu, Mei
Bonassi, Stefano
Neri, Monica
Schwartz, Ann G.
Christiani, David C.
Spitz, Margaret R.
Muscat, Joshua E.
Rennert, Gad
Aben, Katja K.
Andrew, Angeline S.
Bencko, Vladimir
Bickeboeller, Heike
Boffetta, Paolo
Brennan, Paul
Brenner, Hermann
Duell, Eric J.
Fabianova, Eleonora
Field, John K.
Foretova, Lenka
Friis, Soren
Harris, Curtis C.
Holcatova, Ivana
Hong, Yun-Chul
Isla, Dolores
Janout, Vladimir
Kiemeney, Lambertus A.
Kiyohara, Chikako
Lan, Qing
Lazarus, Philip
Lissowska, Jolanta
Le Marchand, Loic
Mates, Dana
Matsuo, Keitaro
Mayordomo, Jose I.
McLaughlin, John R.
Morgenstern, Hal
Mueeller, Heiko
Orlow, Irene
Park, Bernard J.
Pinchev, Mila
Raji, Olaide Y.
Rennert, Hedy S.
Rudnai, Peter
Seow, Adeline
Stucker, Isabelle
Szeszenia-Dabrowska, Neonila
Teare, M. Dawn
Tjonnelan, Anne
Ugolini, Donatella
van der Heijden, Henricus F. M.
Wichmann, Erich
Wiencke, John K.
Woll, Penella J.
Yang, Ping
Zaridze, David
Zhang, Zuo-Feng
Etzel, Carol J.
Hung, Rayjean J.
TI Increased risk of lung cancer in individuals with a family history of
the disease: A pooled analysis from the International Lung Cancer
Consortium
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Article
DE Lung cancer; Familial aggregation
ID POPULATION-BASED COHORT; SUSCEPTIBILITY LOCUS; PROSTATE-CANCER; SEQUENCE
VARIANTS; NEVER-SMOKERS; COLORECTAL-CANCER; BREAST-CANCER; SMOKING;
WOMEN; ASSOCIATION
AB Background and methods: Familial aggregation of lung cancer exists after accounting for cigarette smoking. However, the extent to which family history affects risk by smoking status, histology, relative type and ethnicity is not well described. This pooled analysis included 24 case-control studies in the International Lung Cancer Consortium. Each study collected age of onset/interview, gender, race/ethnicity, cigarette smoking, histology and first-degree family history of lung cancer. Data from 24,380 lung cancer cases and 23,305 healthy controls were analysed. Unconditional logistic regression models and generalised estimating equations were used to estimate odds ratios and 95% confidence intervals.
Results: Individuals with a first-degree relative with lung cancer had a 1.51-fold increase in the risk of lung cancer, after adjustment for smoking and other potential confounders (95% CI: 1.39, 1.63). The association was strongest for those with a family history in a sibling, after adjustment (odds ratios (OR) = 1.82, 95% CI: 1.62, 2.05). No modifying effect by histologic type was found. Never smokers showed a lower association with positive familial history of lung cancer (OR = 1.25, 95% CI: 1.03, 1.52), slightly stronger for those with an affected sibling (OR = 1.44, 95% CI: 1.07, 1.93), after adjustment.
Conclusions: The occurrence of lung cancer among never smokers and similar magnitudes of the effect of family history on lung cancer risk across histological types suggests familial aggregation of lung cancer is independent of those risks associated with cigarette smoking. While the role of genetic variation in the aetiology of lung cancer remains to be fully characterised, family history assessment is immediately available and those with a positive history represent a higher risk group. (c) 2012 Elsevier Ltd. All rights reserved.
C1 [Cote, Michele L.; Schwartz, Ann G.] Wayne State Univ, Sch Med, Detroit, MI 48202 USA.
[Cote, Michele L.; Schwartz, Ann G.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48202 USA.
[Liu, Mei; Spitz, Margaret R.] MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX USA.
[Bonassi, Stefano; Neri, Monica] Clin & Mol Epidemiol IRCCS San Raffaele Pisana, Pisa, Italy.
[Christiani, David C.] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA.
[Muscat, Joshua E.] Penn State Univ, Coll Med, Div Publ Hlth Sci, University Pk, PA 16802 USA.
[Rennert, Gad; Pinchev, Mila; Rennert, Hedy S.] Technion Israel Inst Technol, Bruce Rappaport Fac Med, Haifa, Israel.
[Rennert, Gad; Pinchev, Mila; Rennert, Hedy S.] Technion Israel Inst Technol, Dept Community Med & Epidemiol, Carmel Med Ctr, Haifa, Israel.
[Rennert, Gad; Pinchev, Mila; Rennert, Hedy S.] Technion Israel Inst Technol, CHS Natl Canc Control Ctr, Haifa, Israel.
[Aben, Katja K.] Comprehens Canc Ctr Netherlands, Nijmegen, Netherlands.
[Andrew, Angeline S.] Dartmouth Med Sch, Dept Community & Family Med, Norris Cotton Canc Ctr, Lebanon, NH USA.
[Bencko, Vladimir; Holcatova, Ivana] Charles Univ Prague, Inst Hyg & Epidemiol, Prague, Czech Republic.
[Bickeboeller, Heike] Univ Gottingen, Sch Med, Dept Genet Epidemiol, D-3400 Gottingen, Germany.
[Boffetta, Paolo] Mt Sinai Sch Med, New York, NY USA.
[Bencko, Vladimir; Holcatova, Ivana] IARC, Lyon, France.
[Brenner, Hermann; Mueeller, Heiko] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
[Duell, Eric J.] Catalan Inst Oncol ICO IDIBELL, Unit Nutr Environm & Canc, Barcelona, Spain.
[Field, John K.; Raji, Olaide Y.] Univ Liverpool, Canc Res Ctr, Roy Castle Lung Canc Res Programme, Liverpool L69 3BX, Merseyside, England.
[Harris, Curtis C.] Natl Canc Inst, Mol Genet & Carcinogenesis Sect, Bethesda, MD 20892 USA.
[Hong, Yun-Chul] Seoul Natl Univ, Seoul 151, South Korea.
[Isla, Dolores] Univ Zaragoza, Div Med Oncol, E-50009 Zaragoza, Spain.
[Janout, Vladimir] Palacky Univ Med, Dept Prevent Med, Olomouc, Czech Republic.
[Kiemeney, Lambertus A.; van der Heijden, Henricus F. M.] Radboud Univ Nijmegen, Med Ctr, Dept Urol, Nijmegen, Netherlands.
[Kiemeney, Lambertus A.; van der Heijden, Henricus F. M.] Radboud Univ Nijmegen, Nijmegen Med Ctr, Dept Urol, Nijmegen, Netherlands.
[Kiyohara, Chikako] Kyushu Univ, Dept Basic Med, Fukuoka 812, Japan.
[Lan, Qing] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Lazarus, Philip] Penn State Univ, Penn State Canc Inst, University Pk, PA 16802 USA.
[Lissowska, Jolanta] Maria Sklodowska Curie Inst Oncol, Warsaw, Poland.
[Lissowska, Jolanta] Ctr Canc, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Kiemeney, Lambertus A.; van der Heijden, Henricus F. M.] Radboud Univ Nijmegen, Dept Epidemiol, Nijmegen, Netherlands.
[Kiemeney, Lambertus A.; van der Heijden, Henricus F. M.] Radboud Univ Nijmegen, HTA, Nijmegen, Netherlands.
[Le Marchand, Loic] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Mates, Dana] Inst Publ Hlth, Dept Occupat Hlth, Bucharest, Romania.
[Matsuo, Keitaro] Res Inst, Aichi Canc Ctr, Aichi, Japan.
[McLaughlin, John R.; Hung, Rayjean J.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON, Canada.
[Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA.
[Orlow, Irene] Mem Sloan Kettering Canc, New York, NY USA.
[Park, Bernard J.] Hackensack Univ, Med Ctr, Hackensack, NJ USA.
[Rudnai, Peter] Fodor Jozsef Natl Ctr Publ Hlth, Natl Inst Environm Hlth, Budapest, Hungary.
[Seow, Adeline] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore 117595, Singapore.
[Stucker, Isabelle] INSERM, U170, Dept Environm Epidemiol, Paris, France.
[Szeszenia-Dabrowska, Neonila] Nofer Inst Occupat Med, Lodz, Poland.
[Teare, M. Dawn] Univ Sheffield, Sheffield, S Yorkshire, England.
[Ugolini, Donatella] Univ Genoa, Dipartimento Oncol Biol & Genet, I-16126 Genoa, Italy.
[Wichmann, Erich] German Res Ctr Environm Hlth, Inst Epidemiol, Helmholtz Ctr, Munich, Germany.
[Wiencke, John K.] Univ Calif San Francisco, Dept Epidemiol & Biostatist, San Francisco, CA 94143 USA.
[Yang, Ping] Mayo Clin, Div Epidemiol, Rochester, MN USA.
[Zaridze, David] NN Blokhin Canc Res Ctr, Inst Carcinogenesis, Moscow, Russia.
[Zhang, Zuo-Feng] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA.
[Wichmann, Erich] Univ Munich, IBE, Munich, Germany.
RP Cote, ML (reprint author), Wayne State Univ, Sch Med, Detroit, MI 48202 USA.
EM cotem@karmanos.org; rayjean.hung@lunenfeld.ca
RI Hong, Yun-Chul/J-5725-2012; Hung, Rayjean/A-7439-2013; van der Heijden,
H.F.M. (Erik)/D-3774-2009; Neri, Monica/J-6308-2012; Brenner,
Hermann/B-4627-2017; McLaughlin, John/E-4577-2013; Mayordomo,
Jose/K-3453-2013; Zaridze, David/K-5605-2013; Kiemeney,
Lambertus/D-3357-2009; Janout, Vladimir/M-5133-2014;
Szeszenia-Dabrowska, Neonila/F-7190-2010; Aben, Katja/G-9686-2016
OI Duell, Eric J/0000-0001-5256-0163; mates, dana/0000-0002-6219-9807;
Lissowska, Jolanta/0000-0003-2695-5799; Field, John/0000-0003-3951-6365;
bonassi, stefano/0000-0003-3833-6717; Orlow, Irene/0000-0001-6234-6961;
Matsuo, Keitaro/0000-0003-1761-6314; van der Heijden, H.F.M.
(Erik)/0000-0003-3596-518X; Neri, Monica/0000-0003-4796-3675; Brenner,
Hermann/0000-0002-6129-1572; Woll, Penella/0000-0002-1118-0831;
Kiemeney, Lambertus/0000-0002-2368-1326; Aben, Katja/0000-0002-0214-2147
FU Canadian Cancer Society (CCSRI) [020214]; Cancer Care Ontario Research
Chair Award; Bi-national Israel US Science Foundation (BSF) [2003159];
Baden-Wurttemberg Ministry of Science Research and Arts; Steps for
Breath and the Labrecque Foundation; Society of Memorial Sloan-Kettering
Cancer Center; Polish State Committee for Scientific Research
[SPUBM-COPERNI-CUS/P-05/DZ-30/99/2000]; Weston Park Hospital Charitable
Trust; European Commission (DG-XII) [IC15-CT96-0313]; Radboud University
Nijmegen Medical Centre; [NIH K07 CA125203-01A2]; [NIH R01CA060691];
[NIH R01CA87895]; [NIH N01-PC35145]; [NIH P30CA22453]; [NIH (NCI)
RO1CA74386]; [P50 CA090578]
FX The authors declare no conflicts of interest exist. They do wish to
acknowledge the following support: ILCCO data management is supported by
Canadian Cancer Society (CCSRI no. 020214) and Cancer Care Ontario
Research Chair Award.; M.L.C.: NIH K07 CA125203-01A2.; A.G.S.: NIH
R01CA060691, NIH R01CA87895, NIH N01-PC35145, NIH P30CA22453.; D.C.C.:
Grants: NIH (NCI) RO1CA74386 and P50 CA090578.; G.R.: Grant number
2003159 from the Bi-national Israel US Science Foundation (BSF).; H.B.
and H.M.: ESTHER study was supported by a grant from the
Baden-Wurttemberg Ministry of Science Research and Arts.; I.O.: Steps
for Breath and the Labrecque Foundation; and the Society of Memorial
Sloan-Kettering Cancer Center.; J.L.: The Warsaw study part of the study
was supported by local grant from The Polish State Committee for
Scientific Research, grant no. SPUBM-COPERNI-CUS/P-05/DZ-30/99/2000.;
P.J.W.: ReSoLuCENT study funded by the Weston Park Hospital Charitable
Trust.; Financial support from European Commission (DG-XII), contract
no. IC15-CT96-0313 is gratefully acknowledged.; The Nijmegen Ling Cancer
Study was funded by an investment grant of the Radboud University
Nijmegen Medical Centre.
NR 75
TC 27
Z9 28
U1 3
U2 25
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 2012
VL 48
IS 13
BP 1957
EP 1968
DI 10.1016/j.ejca.2012.01.038
PG 12
WC Oncology
SC Oncology
GA 993UG
UT WOS:000307884500005
PM 22436981
ER
PT J
AU Siahanidou, T
Garatzioti, M
Lazaropoulou, C
Kourlaba, G
Papassotiriou, I
Kino, T
Imura, A
Nabeshima, Y
Chrousos, G
AF Siahanidou, Tania
Garatzioti, Maria
Lazaropoulou, Christina
Kourlaba, Georgia
Papassotiriou, Ioannis
Kino, Tomoshige
Imura, Akihiro
Nabeshima, Yo-ichi
Chrousos, George
TI Plasma soluble alpha-klotho protein levels in premature and term
neonates: correlations with growth and metabolic parameters
SO EUROPEAN JOURNAL OF ENDOCRINOLOGY
LA English
DT Article
ID INSULIN-RESISTANCE; OXIDATIVE STRESS; DEFICIENT MICE; HORMONE KLOTHO;
CORD BLOOD; HOMEOSTASIS; EXPRESSION; DIFFERENTIATION; REGULATOR;
PHOSPHATE
AB Objective: alpha-Klotho (alpha-KL), a protein with antiaging properties, regulates phosphate, calcium, and bone metabolism, induces resistance to oxidative stress, and may participate in insulin signaling. The role of alpha-KL in neonates, known to be prone to metabolic disturbances and oxidative stress, is not known. The aim of this study was to evaluate circulating soluble alpha-KL concentrations in preterm and full-term neonates and unravel possible correlations with growth, metabolism, and indices of oxidative stress.
Design: Prospective study.
Methods: Plasma-soluble alpha-KL levels were determined by specific ELISA in 50 healthy neonates (25 preterm, mean (S.D.) gestational age (GA) 33.7 (1.1) weeks, and 25 full-term infants) at days 14 and 28 of life. Associations of alpha-KL with anthropometric, metabolic parameters, and indices of oxidative stress were examined.
Results: alpha-KL levels were significantly higher in full-term than in preterm infants at both days 14 (1099 (480) pg/ml vs 884 (239) pg/ml respectively; P<0.05) and 28 (1277 (444) pg/ml vs 983 (264) pg/ml respectively; P! 0.01). In both preterm and full-term infants, alpha-KL levels increased significantly from day 14 to 28 of life (P<0.001). Circulating alpha-KL concentrations correlated with GA (beta=0.32, P=0.001), body weight (beta=0.34, P=0.001), body length (beta=0.33, P=0.001), 1,25-dihydroxy-vitamin D level (beta=0.24, P<0.05), and malondialdehyde level (beta=0.20, P<0.05) but not with glucose, insulin, or homeostasis model assessment index of insulin resistance values.
Conclusions: Soluble alpha-KL levels rise as GA and postnatal age advance in neonates and may have an impact on vitamin D metabolism and oxidative stress. Whether alpha-KL may have a role in the regulation of infants' growth should be further studied.
C1 [Siahanidou, Tania; Garatzioti, Maria; Kourlaba, Georgia; Chrousos, George] Univ Athens, Sch Med, Dept Pediat 1, GR-11527 Athens, Greece.
[Lazaropoulou, Christina; Papassotiriou, Ioannis] Aghia Sophia Childrens Hosp, Dept Clin Biochem, Athens 11527, Greece.
[Kino, Tomoshige] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Mol Hormone Act, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Imura, Akihiro; Nabeshima, Yo-ichi] Fdn Biochem Res & Innovat, Inst Biomed Res & Innovat, Lab Mol Life Sci, Kyoto, Japan.
RP Siahanidou, T (reprint author), Univ Athens, Sch Med, Dept Pediat 1, GR-11527 Athens, Greece.
EM siahan@med.uoa.gr
FU University of Athens Special Fund
FX This work was funded by the University of Athens Special Fund. The
funding source played no role in the study design, in the collection,
analysis, and interpretation of data, in the writing of the report, or
in the decision to submit the report for publication.
NR 38
TC 13
Z9 13
U1 1
U2 3
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 0804-4643
J9 EUR J ENDOCRINOL
JI Eur. J. Endocrinol.
PD SEP
PY 2012
VL 167
IS 3
BP 433
EP 440
DI 10.1530/EJE-12-0476
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 001KJ
UT WOS:000308459200017
PM 22715479
ER
PT J
AU Fairfield, KM
Murray, KM
Wierman, HR
Han, PKJ
Hallen, S
Miesfeldt, S
Trimble, EL
Warren, JL
Earle, CC
AF Fairfield, Kathleen M.
Murray, Kimberly M.
Wierman, Heidi R.
Han, Paul K. J.
Hallen, Sarah
Miesfeldt, Susan
Trimble, Edward L.
Warren, Joan L.
Earle, Craig C.
TI Disparities in hospice care among older women dying with ovarian cancer
(vol 125, pg 14, 2012)
SO GYNECOLOGIC ONCOLOGY
LA English
DT Correction
C1 [Fairfield, Kathleen M.; Murray, Kimberly M.; Han, Paul K. J.; Miesfeldt, Susan] Maine Med Ctr, Ctr Outcomes Res & Evaluat, Res Inst, Portland, ME 04102 USA.
[Fairfield, Kathleen M.] Maine Med Ctr, Dept Med, Portland, ME 04102 USA.
[Wierman, Heidi R.; Hallen, Sarah] Maine Med Ctr, Dept Geriatr, Portland, ME 04102 USA.
[Trimble, Edward L.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Warren, Joan L.] NCI, Appl Res Program, Bethesda, MD 20892 USA.
[Earle, Craig C.] Sunnybrook Hlth Sci Ctr, Inst Clin Evaluat Sci, Toronto, ON M4N 3M5, Canada.
RP Fairfield, KM (reprint author), Maine Med Ctr, Ctr Outcomes Res & Evaluat, Res Inst, 39 Forest Ave, Portland, ME 04102 USA.
EM fairfk@mmc.org; wiermh@mmc.org; halles@mmc.org;
trimblet@ctep.nci.nih.gov; joan_warren@nih.gov; craig.earle@ices.on.ca
NR 1
TC 1
Z9 1
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD SEP
PY 2012
VL 126
IS 3
BP 509
EP 510
DI 10.1016/j.ygyno.2012.05.015
PG 2
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 986DU
UT WOS:000307322000035
ER
PT J
AU Kamath, U
Compton, J
Islamaj-Dogan, R
De Jong, KA
Shehu, A
AF Kamath, Uday
Compton, Jack
Islamaj-Dogan, Rezarta
De Jong, Kenneth A.
Shehu, Amarda
TI An Evolutionary Algorithm Approach for Feature Generation from Sequence
Data and Its Application to DNA Splice Site Prediction
SO IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS
LA English
DT Article
DE Evolutionary computation; genetic programming; feature extraction and
construction; classifier design and evaluation; data mining; DNA splice
sites
ID SUPPORT VECTOR MACHINES; FEATURE-SELECTION; GENETIC ALGORITHMS; MUTUAL
INFORMATION; CLASSIFICATION; SIGNALS; MOTIFS
AB Associating functional information with biological sequences remains a challenge for machine learning methods. The performance of these methods often depends on deriving predictive features from the sequences sought to be classified. Feature generation is a difficult problem, as the connection between the sequence features and the sought property is not known a priori. It is often the task of domain experts or exhaustive feature enumeration techniques to generate a few features whose predictive power is then tested in the context of classification. This paper proposes an evolutionary algorithm to effectively explore a large feature space and generate predictive features from sequence data. The effectiveness of the algorithm is demonstrated on an important component of the gene-finding problem, DNA splice site prediction. This application is chosen due to the complexity of the features needed to obtain high classification accuracy and precision. Our results test the effectiveness of the obtained features in the context of classification by Support Vector Machines and show significant improvement in accuracy and precision over state-of-the-art approaches.
C1 [Kamath, Uday] George Mason Univ, Dept Comp Sci, Ashburn, VA 20147 USA.
[Compton, Jack] Barquin Int, Alexandria, VA 22310 USA.
[Islamaj-Dogan, Rezarta] NIH, NCBI, Natl Lib Med, Bethesda, MD 20894 USA.
[De Jong, Kenneth A.; Shehu, Amarda] George Mason Univ, Dept Comp Sci, Fairfax, VA 22030 USA.
RP Kamath, U (reprint author), George Mason Univ, Dept Comp Sci, 20929 Ivymount Terrace, Ashburn, VA 20147 USA.
EM ukamath@gmu.edu; jack.compton@gmail.com; Rezarta.Islamaj@nih.gov;
kdejong@gmu.edu; amarda@gmu.edu
OI Islamaj Dogan, Rezarta/0000-0001-5651-1860; Shehu,
Amarda/0000-0001-5230-4610
NR 54
TC 15
Z9 16
U1 1
U2 13
PU IEEE COMPUTER SOC
PI LOS ALAMITOS
PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA
SN 1545-5963
J9 IEEE ACM T COMPUT BI
JI IEEE-ACM Trans. Comput. Biol. Bioinform.
PD SEP-OCT
PY 2012
VL 9
IS 5
BP 1387
EP 1398
DI 10.1109/TCBB.2012.53
PG 12
WC Biochemical Research Methods; Computer Science, Interdisciplinary
Applications; Mathematics, Interdisciplinary Applications; Statistics &
Probability
SC Biochemistry & Molecular Biology; Computer Science; Mathematics
GA 985VS
UT WOS:000307299200014
PM 22508909
ER
PT J
AU Ronca, R
Kotsyfakis, M
Lombardo, F
Rizzo, C
Curra, C
Ponzi, M
Fiorentino, G
Ribeiro, JMC
Arca, B
AF Ronca, Raffaele
Kotsyfakis, Michalis
Lombardo, Fabrizio
Rizzo, Cinzia
Curra, Chiara
Ponzi, Marta
Fiorentino, Gabriella
Ribeiro, Jose M. C.
Arca, Bruno
TI The Anopheles gambiae cE5, a tight- and fast-binding thrombin inhibitor
with post-transcriptionally regulated salivary-restricted expression
SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
LA English
DT Article
DE Anopheles; Salivary protein; Anti-thrombin; Anophelin; Hematophagy;
Post-transcriptional regulation
ID ADULT FEMALE MOSQUITO; MALARIA VECTOR; INSIGHT; MICRORNAS; SEQUENCES;
STEPHENSI; FUNESTUS; PROTEINS; SIALOME; CLONING
AB Mosquito saliva carries a large number of factors with anti-hemostatic, anti-inflammatory and immunomodulatory activities. The cE5 protein was initially identified during an Anopheles gambiae salivary gland transcriptome study and later shown to share sequence similarity with anophelin, a thrombin inhibitor from the saliva of the New World mosquito Anopheles albimanus. The cE5 gene was found to encode different mRNA isoforms coexisting in several tissues of both male and female mosquitoes, a highly unusual profile for a gene potentially encoding an anti-thrombin and involved in blood feeding. Expression of the cE5 protein and assessment of its activity and inhibitory properties showed that it is a highly specific and tight-binding thrombin inhibitor, which differs from the A. albimanus orthologue for the fast-binding kinetics. Despite the widespread occurrence of cE5 transcripts in different mosquito tissues the corresponding protein was only found in female salivary glands, where it undergoes post-translational modification. Therefore, tissue-specific restriction of the A. gambiae cE5 is not achieved by transcriptional control, as common for mosquito salivary genes involved in hematophagy, but by post-trascriptional gene regulatory mechanisms. Our observations provide a paradigm of post-transcriptional regulation as key determinant of tissue specificity for a protein from an important disease vector and point out that transcriptomic data should be interpreted with caution in the absence of concomitant proteomic support. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Lombardo, Fabrizio; Rizzo, Cinzia; Arca, Bruno] Univ Roma La Sapienza, Dept Publ Hlth & Infect Dis, Parasitol Sect, I-00185 Rome, Italy.
[Kotsyfakis, Michalis] Acad Sci Czech Republic, Inst Parasitol, Ctr Biol, CR-37005 Ceske Budejovice, Czech Republic.
[Curra, Chiara; Ponzi, Marta] Ist Super Sanita, Dipartimento Malattie Infett Pamssitarie & Immuno, I-00161 Rome, Italy.
[Ribeiro, Jose M. C.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Ronca, Raffaele; Fiorentino, Gabriella; Arca, Bruno] Univ Naples Federico II, Dept Struct & Funct Biol, I-80126 Naples, Italy.
RP Arca, B (reprint author), Univ Roma La Sapienza, Dept Publ Hlth & Infect Dis, Parasitol Sect, Piazzale Aldo Moro 5, I-00185 Rome, Italy.
EM bruno.arca@uniroma1.it
RI Kotsyfakis, Michail/G-9525-2014; Lombardo, Fabrizio/J-8511-2014;
Ribeiro, Jose/J-7011-2015; Fiorentino, Gabriella/E-2843-2017;
OI Kotsyfakis, Michail/0000-0002-7526-1876; Lombardo,
Fabrizio/0000-0002-8563-0612; Fiorentino, Gabriella/0000-0002-4089-3822;
Arca, Bruno/0000-0002-4029-0984; Ronca, Raffaele/0000-0003-2217-3378;
Curra, Chiara/0000-0001-7851-1087; Ribeiro, Jose/0000-0002-9107-0818
FU European Union BioMalPar [503578]; Infravec [228421]; Intramural
Research Program of the Division of Intramural Research, NIAID-NIH; Jan
Evangelista Purkyne fellowship; National Academy of Sciences of the
Czech Republic [Z60220518]; Grant Agency of the Czech Republic
[P502/12/2409]; European Union [PIRG07-GA-2010-268177]; NIH
[R01AI09365]; Infravec project; Istituto Pasteur-Fondazione
Cenci-Bolognetti (Sapienza University, Rome)
FX This work was supported by the European Union BioMalPar (503578) and
Infravec (228421) grants to BA. JMCR received support from the
Intramural Research Program of the Division of Intramural Research,
NIAID-NIH. MK received support by a Jan Evangelista Purkyne fellowship,
by the National Academy of Sciences of the Czech Republic (Z60220518),
by the Grant Agency of the Czech Republic (P502/12/2409), by a European
Union MC Reintegration grant (PIRG07-GA-2010-268177) and from NIH
(R01AI093653). RR was supported by the Infravec project. CR was partly
supported by a short term fellowship of Istituto Pasteur-Fondazione
Cenci-Bolognetti (Sapienza University, Rome).
NR 32
TC 6
Z9 6
U1 2
U2 9
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0965-1748
J9 INSECT BIOCHEM MOLEC
JI Insect Biochem. Mol. Biol.
PD SEP
PY 2012
VL 42
IS 9
BP 610
EP 620
DI 10.1016/j.ibmb.2012.04.008
PG 11
WC Biochemistry & Molecular Biology; Entomology
SC Biochemistry & Molecular Biology; Entomology
GA 998WT
UT WOS:000308271800002
PM 22617725
ER
PT J
AU Gungor, D
Bornstein, MH
Phalet, K
AF Gungor, Derya
Bornstein, Marc H.
Phalet, Karen
TI Religiosity, values, and acculturation: A study of Turkish,
Turkish-Belgian, and Belgian adolescents
SO INTERNATIONAL JOURNAL OF BEHAVIORAL DEVELOPMENT
LA English
DT Article
DE acculturation; cultural values; religiosity; Turkish Belgians
ID INTERGENERATIONAL TRANSMISSION; WESTERN-EUROPE; DUTCH MUSLIMS; 20
COUNTRIES; IDENTITY; IDENTIFICATION; 2ND-GENERATION; NETHERLANDS;
TRANSITIONS; PERSISTENCE
AB We address the understudied religious dimension of acculturation in acculturating adolescents who combine a religious Islamic heritage with a secularized Christian mainstream culture. The religiosity of 197 Turkish-Belgian adolescents was compared with that of 366 age-mates in Turkey (the heritage culture) and 203 in Belgium (the mainstream culture) and related to cultural values, acculturation orientations, and ethnic identification. Belgian adolescents showed lower and declining religiosity with age, whereas Turkish and Turkish-Belgian adolescents were more religious regardless of age. Acculturating adolescents reaffirmed religion as compared with monocultural adolescents in Turkey. Religious reaffirmation was related to cultural values of interdependence, heritage culture maintenance, and ethnic identification.
C1 [Gungor, Derya] Katholieke Univ Leuven, Ctr Social & Cultural Psychol, B-3000 Louvain, Belgium.
[Bornstein, Marc H.] NICHD, NIH, Bethesda, MD 20892 USA.
RP Gungor, D (reprint author), Katholieke Univ Leuven, Ctr Social & Cultural Psychol, Tiensestr 102, B-3000 Louvain, Belgium.
EM Derya.Gungor@ppw.kuleuven.be
FU Intramural NIH HHS [ZIA HD001119-25]
NR 47
TC 11
Z9 11
U1 3
U2 28
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0165-0254
J9 INT J BEHAV DEV
JI Int. J. Behav. Dev.
PD SEP
PY 2012
VL 36
IS 5
BP 367
EP 373
DI 10.1177/0165025412448357
PG 7
WC Psychology, Developmental
SC Psychology
GA 995CV
UT WOS:000307985800005
PM 23155300
ER
PT J
AU Fleg, JL
Stone, GW
Fayad, ZA
Granada, JF
Hatsukami, TS
Kolodgie, FD
Ohayon, J
Pettigrew, R
Sabatine, MS
Tearney, GJ
Waxman, S
Domanski, MJ
Srinivas, PR
Narula, J
AF Fleg, Jerome L.
Stone, Gregg W.
Fayad, Zahi A.
Granada, Juan F.
Hatsukami, Thomas S.
Kolodgie, Frank D.
Ohayon, Jacques
Pettigrew, Roderic
Sabatine, Marc S.
Tearney, Guillermo J.
Waxman, Sergio
Domanski, Michael J.
Srinivas, Pothur R.
Narula, Jagat
TI Detection of High-Risk Atherosclerotic Plaque Report of the NHLBI
Working Group on Current Status and Future Directions
SO JACC-CARDIOVASCULAR IMAGING
LA English
DT Article
DE cardiovascular event; high-risk plaque; imaging; prognosis; vulnerable
plaque
ID CORONARY-ARTERY-DISEASE; OPTICAL COHERENCE TOMOGRAPHY; INFRARED
SPECTROSCOPY SYSTEM; POSITRON-EMISSION-TOMOGRAPHY; RADIOFREQUENCY
DATA-ANALYSIS; C-REACTIVE PROTEIN; INTRAVASCULAR ULTRASOUND; VULNERABLE
PLAQUE; CAROTID PLAQUE; MYOCARDIAL-INFARCTION
AB The leading cause of major morbidity and mortality in most countries around the world is atherosclerotic cardiovascular disease, most commonly caused by thrombotic occlusion of a high-risk coronary plaque resulting in myocardial infarction or cardiac death, or embolization from a high-risk carotid plaque resulting in stroke. The lesions prone to result in such clinical events are termed vulnerable or high-risk plaques, and their identification may lead to the development of pharmacological and mechanical intervention strategies to prevent such events. Autopsy studies from patients dying of acute myocardial infarction or sudden death have shown that such events typically arise from specific types of atherosclerotic plaques, most commonly the thin-cap fibroatheroma. However, the search in human beings for vulnerable plaques before their becoming symptomatic has been elusive. Recently, the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study demonstrated that coronary plaques that are likely to cause future cardiac events, regardless of angiographic severity, are characterized by large plaque burden and small lumen area and/or are thin-cap fibroatheromas verified by radiofrequency intravascular ultrasound imaging. This study opened the door to identifying additional invasive and noninvasive imaging modalities that may improve detection of high-risk atherosclerotic lesions and patients. Beyond classic risk factors, novel biomarkers and genetic profiling may identify those patients in whom noninvasive imaging for vulnerable plaque screening, followed by invasive imaging for risk confirmation is warranted, and in whom future pharmacological and/or device-based focal or regional therapies may be applied to improve long-term prognosis. (J Am Coll Cardiol Img 2012;5:941-55) (C) 2012 by the American College of Cardiology Foundation
C1 [Fleg, Jerome L.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Stone, Gregg W.; Granada, Juan F.] Columbia Univ, Med Ctr, New York, NY USA.
[Stone, Gregg W.; Granada, Juan F.] Cardiovasc Res Fdn, New York, NY USA.
[Fayad, Zahi A.; Domanski, Michael J.; Narula, Jagat] Mt Sinai Sch Med, New York, NY USA.
[Hatsukami, Thomas S.] Univ Washington, Seattle, WA 98195 USA.
[Kolodgie, Frank D.] Cardiovasc Pathol Inst, Gaithersburg, MD USA.
[Ohayon, Jacques; Pettigrew, Roderic] NIDDKD, Bethesda, MD 20892 USA.
[Sabatine, Marc S.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Sabatine, Marc S.; Tearney, Guillermo J.] Harvard Univ, Sch Med, Boston, MA USA.
[Tearney, Guillermo J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Waxman, Sergio] Lahey Clin Fdn, Boston, MA USA.
RP Fleg, JL (reprint author), NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr,Room 8150, Bethesda, MD 20892 USA.
EM flegj@nhlbi.nih.gov; narula@mountsinai.org
FU Brigham and Women's Hospital from Abbott Laboratories; Amgen;
AstraZeneca; BRAHMS; Bristol-Myers Squibb/Sanofi-Aventis Joint Venture;
Critical Diagnostics; Daiichi-Sankyo; Merck; Roche Diagnostics; Takeda;
Nanosphere; Terumo Corporation
FX Dr. Stone has been a consultant to InfraReDx, Boston Scientific, Abbott
Vascular, Medtronic, and Volcano. Dr. Sabatine has received research
grant support (>$25,000) through Brigham and Women's Hospital from
Abbott Laboratories, Amgen, AstraZeneca, BRAHMS, Bristol-Myers
Squibb/Sanofi-Aventis Joint Venture, Critical Diagnostics,
Daiichi-Sankyo, Merck, Roche Diagnostics, and Takeda; has served on the
scientific advisory board (<$10,000) for Bristol-Myers
Squibb/Sanofi-Aventis Joint Venture, GlaxoSmithKline, Merck, and Pfizer;
and (>$10,000) Sanofi-Aventis; and has received research support
(>$25,000) from Nanosphere. Dr. Tearney has been a consultant to Samsung
and Merck; has performed sponsored research for Terumo Corporation; and
has the right to receive royalties from Terumo Corporation and MIT. Dr.
Narula serves on the advisory boards of GE, Philips, and Siemens
Healthcare. All other authors have reported that they have no
relationships relevant to the contents of this paper to disclose. H.
William Strauss, MD, served as Guest Editor for this paper.
NR 78
TC 71
Z9 76
U1 1
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1936-878X
J9 JACC-CARDIOVASC IMAG
JI JACC-Cardiovasc. Imag.
PD SEP
PY 2012
VL 5
IS 9
BP 941
EP 955
DI 10.1016/j.jcmg.2012.07.007
PG 15
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 003DX
UT WOS:000308589500013
PM 22974808
ER
PT J
AU Wechsler, ME
Fulkerson, PC
Bochner, BS
Gauvreau, GM
Gleich, GJ
Henkel, T
Kolbeck, R
Mathur, SK
Ortega, H
Patel, J
Prussin, C
Renzi, P
Rothenberg, ME
Roufosse, F
Simon, D
Simon, HU
Wardlaw, A
Weller, PF
Klion, AD
AF Wechsler, Michael E.
Fulkerson, Patricia C.
Bochner, Bruce S.
Gauvreau, Gail M.
Gleich, Gerald J.
Henkel, Tim
Kolbeck, Roland
Mathur, Sameer K.
Ortega, Hector
Patel, Jatin
Prussin, Calman
Renzi, Paolo
Rothenberg, Marc E.
Roufosse, Florence
Simon, Dagmar
Simon, Hans-Uwe
Wardlaw, Andrew
Weller, Peter F.
Klion, Amy D.
TI Novel targeted therapies for eosinophilic disorders
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Hypereosinophilic syndromes; eosinophil-associated gastrointestinal
disorders; eosinophilic esophagitis; Churg-Strauss syndrome; IL-5;
mepolizumab; reslizumab
ID IDIOPATHIC HYPEREOSINOPHILIC SYNDROME; ANTI-IL-5 MEPOLIZUMAB THERAPY;
CHURG-STRAUSS-SYNDROME; T-CELL POPULATION; AIRWAY INFLAMMATION;
PERIPHERAL-BLOOD; ANTI-INTERLEUKIN-5 ANTIBODY; INHIBITORY RECEPTORS;
ALEMTUZUMAB THERAPY; MONOCLONAL-ANTIBODY
AB Hypereosinophilic syndromes (HESs) are a diverse group of conditions characterized by clinical manifestations attributable to eosinophilia and eosinophilic infiltration of tissues. HESs are chronic disorders with significant morbidity and mortality. Although the availability of targeted chemotherapeutic agents, including imatinib, has improved quality of life and survival in some patients with HESs, additional agents with increased efficacy and decreased toxicity are sorely needed. The purpose of this review is to provide an overview of eosinophil biology with an emphasis on potential targets of pharmacotherapy and to provide a summary of potential eosinophil-targeting agents, including those in development, in clinical trials, or approved for other disorders. (J Allergy Clin Immunol 2012;130:563-71.)
C1 [Wechsler, Michael E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA.
[Fulkerson, Patricia C.; Rothenberg, Marc E.] Cincinnati Childrens Hosp, Med Ctr, Dept Pediat, Div Allergy & Immunol, Baltimore, MD USA.
[Bochner, Bruce S.] Johns Hopkins Univ, Sch Med, Dept Med, Div Clin Immunol & Allergy, Baltimore, MD 21205 USA.
[Gauvreau, Gail M.] McMaster Univ, Hamilton, ON L8S 4L8, Canada.
[Gleich, Gerald J.] Univ Utah, Dept Dermatol & Med, Salt Lake City, UT USA.
[Henkel, Tim] Ceptaris Therapeut, Malvern, PA USA.
[Kolbeck, Roland] MedImmune Resp Inflammat & Autoimmun, Gaithersburg, MD USA.
[Mathur, Sameer K.] Univ Wisconsin, Sch Med, Dept Med, Div Allergy Pulm & Crit Care, Madison, WI 53706 USA.
[Ortega, Hector] GlaxoSmithKline Res & Dev Ltd, Res Triangle Pk, NC USA.
[Patel, Jatin] GlaxoSmithKline Res & Dev Ltd, Uxbridge, Middx, England.
[Prussin, Calman] NIAID, Lab Allerg Dis, Bethesda, MD 20892 USA.
[Renzi, Paolo] Univ Montreal, Notre Dame Hosp, Montreal, PQ H3C 3J7, Canada.
[Roufosse, Florence] Univ Libre Brussels, Erasme Hosp, Dept Internal Med, Brussels, Belgium.
[Roufosse, Florence] Univ Libre Brussels, Inst Med Immunol, Gosselies, Belgium.
[Simon, Dagmar] Univ Hosp Bern, Dept Dermatol, Inselspital, Bern, Switzerland.
[Simon, Hans-Uwe] Univ Bern, Inst Pharmacol, CH-3012 Bern, Switzerland.
[Wardlaw, Andrew] Univ Leicester, Inst Lung Hlth, Dept Infect Immun & Inflammat, Leicester LE1 7RH, Leics, England.
[Weller, Peter F.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA.
[Klion, Amy D.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Wechsler, ME (reprint author), Div Hlth, 1400 Jackson St, Denver, CO 80206 USA.
EM mikewechsler@gmail.com
RI Wechsler, Michael /B-3979-2013;
OI Wechsler, Michael /0000-0003-3505-2946; Prussin,
Calman/0000-0002-3917-3326; Simon, Hans-Uwe/0000-0002-9404-7736; Klion,
Amy/0000-0002-4986-5326; Wardlaw, Andrew/0000-0001-6583-0791
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases/National Institutes of Health (NIH); Office of Rare
Diseases/NIH; National Institutes of Health (NIH); GlaxoSmithKline;
Cephalon; Novartis; Sepracor/Sunovion; Schering-Plough; NKT
Therapeutics; Asthmatx/BSCI; Genzyme; MapPharma; Genentech; Boehringer
Ingelheim; National Institute of Allergy and Infectious Diseases;
National Heart, Lung, and Blood Institute; UpToDate; Elsevier; Topigen
Pharma; TRIA Bioscience Corp; ImmViz; Teva; Teva Pharmaceuticals; NIH;
Pharmaxis; Immune Pharmaceuticals; UpToDate Online; OPO Foundation
Zurich; Basilea Pharmaceutica; Pfizer
FX Supported in part by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases/National Institutes of
Health (NIH), and by the Office of Rare Diseases/NIH.; M. E. Wechsler
has received research support from the National Institutes of Health
(NIH); has received consulting fees from GlaxoSmithKline, Cephalon,
Novartis, Sepracor/Sunovion, Schering-Plough, NKT Therapeutics,
Asthmatx/BSCI, Genzyme, MapPharma, Genentech, and Boehringer Ingelheim;
and has received honoraria from Merck. B. S. Bochner has received grants
from the National Institute of Allergy and Infectious Diseases and the
National Heart, Lung, and Blood Institute; has consultant arrangements
with Sanofi-Aventis, Genentech, Merck, Roche, GlaxoSmithKline, TEVA,
GlycoFi, and Medicis; is on a scientific advisory board for Merck; is a
coinventor on existing and pending Siglec-8-related patents; might be
entitled to a share of royalties received by his university on the
potential sales of Siglec-8-related products but thus far has received
no such royalties; receives royalties from UpToDate and Elsevier; is a
cofounder of and has purchased stock in Allakos; and holds stock options
for Glycomimetics. G. M. Gauvreau has received research support from
Topigen Pharma. G. J. Gleich is a board member of the American
Partnership for Eosinophilic Disorders (APFED) without compensation; has
received consultancy fees from GlaxoSmithKline; has received research
support from TRIA Bioscience Corp and ImmViz; has a patent with ImmViz;
has received royalties from Teva; and has stock/stock options in Immune
Design Corp. T. Henkel has received consultancy fees from Cephalon and
is employed by and has received stock/stock options in Ception
Therapeutics. R. Kolbeck is employed by and owns stock/stock options in
MedImmune. S. K. Mathur has received consultancy fees from Teva
Pharmaceuticals, is employed by the University of Wisconsin and William
S Middleton VA Hospital, and has received research support from the NIH.
H. Ortega is employed by and has received stock/stock options in
GlaxoSmithKline. P. Renzi has received research support, consulting
fees, and fees for participation in review activities from Pharmaxis and
has received royalties and owns a patent as the inventor of TPI-ASM8. M.
E. Rothenberg is a member of the board for APFED and the International
Eosinophil Society, has received consultancy fees from Immune
Pharmaceuticals, is the inventor of patents owned by Cincinnati
Children's, and has stock/stock options in Immune Pharmaceuticals and
Teva. F. Roufosse has received consulting fees and travel support from
GlaxoSmithKline and received royalties from UpToDate Online. D. Simon
has provided expert testimony for Basilea Pharmaceutica and Astellas
Schweiz, has received research support from OPO Foundation Zurich, and
has received lecture fees from Basilea Pharmaceutica. H.-U. Simon has
received consultancy fees from Pfizer. P. F. Weller has received
consultancy fees from GlaxoSmithKline and receives royalties from
UpToDate. A. Wardlaw was a member of the Cephalon-Teva data monitoring
board; has received research support from Pfizer and GlaxoSmithKline;
and has provided legal consultation/expert witness testimony for Bayer.
The rest of the authors declare that they have no relevant conflicts of
interest.
NR 83
TC 42
Z9 46
U1 1
U2 11
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 2012
VL 130
IS 3
BP 563
EP 571
DI 10.1016/j.jaci.2012.07.027
PG 9
WC Allergy; Immunology
SC Allergy; Immunology
GA 001LZ
UT WOS:000308463500001
PM 22935585
ER
PT J
AU Bochner, BS
Book, W
Busse, WW
Butterfield, J
Furuta, GT
Gleich, GJ
Klion, AD
Lee, JJ
Leiferman, KM
Minnicozzi, M
Moqbel, R
Rothenberg, ME
Schwartz, LB
Simon, HU
Wechsler, ME
Weller, PF
AF Bochner, Bruce S.
Book, Wendy
Busse, William W.
Butterfield, Joseph
Furuta, Glenn T.
Gleich, Gerald J.
Klion, Amy D.
Lee, James J.
Leiferman, Kristin M.
Minnicozzi, Michael
Moqbel, Redwan
Rothenberg, Marc E.
Schwartz, Lawrence B.
Simon, Hans-Uwe
Wechsler, Michael E.
Weller, Peter F.
TI Workshop report from the National Institutes of Health Taskforce on the
Research Needs of Eosinophil-Associated Diseases (TREAD)
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Eosinophil; apoptosis; therapeutics; research; discovery; fusion
oncoproteins; hypereosinophilic syndromes; Churg-Strauss syndrome;
coagulopathy
ID CHURG-STRAUSS-SYNDROME; HYPEREOSINOPHILIC SYNDROME; EPISODIC ANGIOEDEMA;
CONSENSUS RECOMMENDATIONS; ESOPHAGEAL EOSINOPHILIA; TREATMENT OPTION;
THE-LITERATURE; PATHOGENESIS; CELL; MEPOLIZUMAB
AB Background: Eosinophils are blood cells that are often found in high numbers in the tissues of allergic conditions and helminthic parasite infections. The pathophysiologic roles that eosinophils may serve in other human "eosinophil-associated" diseases remain obscure.
Objective: National Institutes of Health (NIH) Institutes and the Office of Disease Prevention assembled an international taskforce of clinical and basic scientists with the charge to propose and prioritize unmet research needs in eosinophil-associated diseases.
Methods: The taskforce used an organ system approach to identify the different and common themes of eosinophil cell involvement in these diseases. In early 2012, a draft document was circulated for review. The document was amended and the prioritizations were set at a NIH-organized workshop in June 2012.
Results: The taskforce identified significant research needs. These needs cross disease entities but some are disease specific. There are substantial shortcomings to the various preclinical animal models, as well as significant gaps in our epidemiologic, pathophysiologic, diagnostic, prognostic, and therapeutic knowledge. The taskforce recognized that recent efforts by patient advocacy groups have played instrumental roles in improving the identification and characterization of these disorders. However, communications among the eosinophil-interested communities, for example, governmental funding and regulatory agencies, and industry and clinician scientists need to be more comprehensive.
Conclusions: Significant efforts are required to address our knowledge gaps to improve the outcomes of eosinophil-associated diseases. NIH Institutes, other federal agencies, lay organizations, and the pharmaceutical industry should consider the taskforce's recommendations in their future research activities. (J Allergy Clin Immunol 2012;130:587-96.)
C1 [Bochner, Bruce S.] Johns Hopkins Asthma & Allergy Ctr, Div Allergy & Clin Immunol, Dept Med, Baltimore, MD 21224 USA.
[Book, Wendy] Amer Partnership Eosinophil Disorders, Atlanta, GA USA.
[Busse, William W.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Div Clin Immunol & Allergy, Madison, WI USA.
[Butterfield, Joseph] Mayo Clin, Dept Med, Div Allerg Dis, Rochester, MN USA.
[Furuta, Glenn T.] Univ Colorado, Sch Med,Sect Pediat Gastroenterol Hepatol & Nutr, Dept Pediat,Gastrointestinal Eosinophil Dis Progr, Childrens Hosp,Digest Hlth Inst,Natl Jewish Hlth, Aurora, CO USA.
[Gleich, Gerald J.; Leiferman, Kristin M.] Univ Utah, Hlth Sci Ctr, Dept Dermatol, Salt Lake City, UT USA.
[Klion, Amy D.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Lee, James J.] Mayo Clin Arizona, Div Pulm Med, Dept Biochem & Mol Biol, Scottsdale, AZ USA.
[Moqbel, Redwan] Univ Manitoba, Fac Med, Dept Immunol, Winnipeg, MB R3E 0W3, Canada.
[Rothenberg, Marc E.] Univ Cincinnati, Coll Med, Dept Pediat, Div Allergy & Immunol,Cincinnati Childrens Hosp M, Cincinnati, OH USA.
[Schwartz, Lawrence B.] Virginia Commonwealth Univ, Dept Internal Med, Div Rheumatol Allergy & Immunol, Richmond, VA 23284 USA.
[Simon, Hans-Uwe] Univ Bern, Inst Pharmacol, Bern, Switzerland.
[Wechsler, Michael E.] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care, Boston, MA 02115 USA.
[Wechsler, Michael E.] Harvard Univ, Sch Med, Boston, MA USA.
[Weller, Peter F.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med,Div Allergy & Inflammat,Div Infect Dis, Boston, MA 02215 USA.
RP Bochner, BS (reprint author), Johns Hopkins Asthma & Allergy Ctr, Div Allergy & Clin Immunol, Dept Med, 5501 Hopkins Bayview Circle, Baltimore, MD 21224 USA.
EM bbochner@jhmi.edu
RI Wechsler, Michael /B-3979-2013;
OI Wechsler, Michael /0000-0003-3505-2946; Simon,
Hans-Uwe/0000-0002-9404-7736; Klion, Amy/0000-0002-4986-5326
FU National Institute of Allergy and Infectious Diseases; Office of Disease
Prevention; National Institute of Allergy and Infectious Diseases
(NIAID); National Heart, Lung, and Blood Institute; UpToDate; Elsevier;
Abbott Nutrition; Nutricia; National Institutes of Health (NIH)/NIAID;
Mayo Clinic; TRIA Bioscience Corp; ImmViz; Teva; National Institutes of
Health; Mayo Foundation for Medical Education and Research; CIHR
(Canada); MHRC; MICH; NIH; GlaxoSmithKline; Genentech; Carolus; NeilMed
FX Supported by the National Institute of Allergy and Infectious Diseases
and the Office of Disease Prevention.; B. S. Bochner has received grants
from the National Institute of Allergy and Infectious Diseases (NIAID)
and the National Heart, Lung, and Blood Institute; has consultant
arrangements with Sanofi-Aventis, Genentech, Merck, Roche,
GlaxoSmithKline, TEVA, GlycoFi, and Medicis; is on scientific advisory
boards for Merck and Allakos; is a co-inventor on existing and pending
Siglec-8 related patents; may be entitled to a share of royalties on the
potential sales of Siglec-8-related products; receives royalties from
UpToDate and Elsevier; is a co-founder of and has purchased stock in
Allakos, Inc; and holds stock options for Glycomimetics, Inc. W. M. Book
has received public education grants on behalf of the American
Partnership for Eosinophilic Disorders from Abbott Nutrition and
Nutricia. W. W. Busse has received grants from the National Institutes
of Health (NIH)/NIAID; has served on an advisory board for Merck; has
consulted for Amgen, AstraZeneca, Novartis, GlaxoSmithKline, MedImmune,
and Genentech; and has received royalties from Elsevier. J. Butterfield
has received royalty payments for licensing of technology from the Mayo
Clinic. G. J. Gleich is on the board of the American Partnership for
Eosinophilic Disorders; has consulted for GlaxoSmithKline; has received
grants from TRIA Bioscience Corp and ImmViz; has patent agreements with
ImmViz; has received royalties from Teva; and has stock or stock options
in Immune Design Corp. J. J. Lee has received grants from the National
Institutes of Health and royalties from the Mayo Foundation for Medical
Education and Research. K. M. Leiferman is co-director for the
Immunodermatology Laboratory, Department of Dermatology; has received
payment for lectures from the American Academy of Allergy, Asthma, &
Immunology/American College of Allergy, Asthma, & Immunology Joint Board
Review Course 2012; has a patent with ImmViz; and is the spouse of
co-author Gerald Gleich. R. Moqbel has consulted for GlaxoSmithKline
Canada; has received grants from CIHR (Canada), MHRC, and MICH; and
holds a patent on diagnosing respiratory diseases with urine metabolites
identified by nuclear magnetic resonance. M. E. Rothenberg is Chief
Scientific Officer of Immune Pharmaceuticals; has consultant
arrangements with TEVA Pharmaceuticals; has received grants from the
NIH; is the inventor of patents owned by Cincinnati Children's Hospital
Medical Center; and has stock/stock options in IMMUNE Pharmaceuticals.
L. Schwartz has received grants from GlaxoSmithKline, Genentech,
Carolus, and NeilMed; has received support for travel from the NIH; is
president of the Clinical Immunology Society; is a board member of the
Asthma & Allergy Foundation of America; has consultant arrangements with
Genentech, Marshall Edwards Inc, and Sanofi-Aventis; and receives
royalties from ThermoFisher, Hycult & BioLegend, and Millpore. H.-U.
Simon has consultant arrangements with Pfizer. M. Wechsler has received
grants from the NIH; has consultant arrangements with GlaxoSmithKline,
Cephalon, Novartis, Sepracor/Sunovion, Schering Plough, NKT
Therapeutics, Asthmatx/BSCI, Genzyme, Map-Pharma, Genentech, and
Boehringer Ingelheim; and has received honoraria from Merck. P. Weller
has consultant arrangements with GlaxoSmithKline. The rest of the
authors declare that they have no relevant conflicts of interest.
NR 57
TC 18
Z9 18
U1 0
U2 4
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 2012
VL 130
IS 3
BP 587
EP 596
DI 10.1016/j.jaci.2012.07.024
PG 10
WC Allergy; Immunology
SC Allergy; Immunology
GA 001LZ
UT WOS:000308463500003
PM 22935587
ER
PT J
AU Valent, P
Klion, AD
Horny, HP
Roufosse, F
Gotlib, J
Weller, PF
Hellmann, A
Metzgeroth, G
Leiferman, KM
Arock, M
Butterfield, JH
Sperr, WR
Sotlar, K
Vandenberghe, P
Haferlach, T
Simon, HU
Reiter, A
Gleich, GJ
AF Valent, Peter
Klion, Amy D.
Horny, Hans-Peter
Roufosse, Florence
Gotlib, Jason
Weller, Peter F.
Hellmann, Andrzej
Metzgeroth, Georgia
Leiferman, Kristin M.
Arock, Michel
Butterfield, Joseph H.
Sperr, Wolfgang R.
Sotlar, Karl
Vandenberghe, Peter
Haferlach, Torsten
Simon, Hans-Uwe
Reiter, Andreas
Gleich, Gerald J.
TI Contemporary consensus proposal on criteria and classification of
eosinophilic disorders and related syndromes
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Hypereosinophilic syndrome; eosinophilic leukemia; criteria;
classification; hypereosinophilia of undetermined significance
ID IDIOPATHIC HYPEREOSINOPHILIC SYNDROME; CHRONIC MYELOPROLIFERATIVE
DISEASES; GROWTH-FACTOR RECEPTOR; CHURG-STRAUSS-SYNDROME; TYROSINE
KINASE; SYSTEMIC MASTOCYTOSIS; FAMILIAL EOSINOPHILIA;
GASTROINTESTINAL-TRACT; FIP1L1-PDGFRA FUSION; EPISODIC ANGIOEDEMA
AB Eosinophilia is an important indicator of various neoplastic and nonneoplastic conditions. Depending on the underlying disease and mechanisms, eosinophil infiltration can lead to organ dysfunction, clinical symptoms, or both. During the past 2 decades, several different classifications of eosinophilic disorders and related syndromes have been proposed in various fields of medicine. Although criteria and definitions are, in part, overlapping, no global consensus has been presented to date. The Year 2011 Working Conference on Eosinophil Disorders and Syndromes was organized to update and refine the criteria and definitions for eosinophilic disorders and to merge prior classifications in a contemporary multidisciplinary schema. A panel of experts from the fields of immunology, allergy, hematology, and pathology contributed to this project. The expert group agreed on unifying terminologies and criteria and a classification that delineates various forms of hypereosinophilia, including primary and secondary variants based on specific hematologic and immunologic conditions, and various forms of the hypereosinophilic syndrome. For patients in whom no underlying disease or hypereosinophilic syndrome is found, the term hypereosinophilia of undetermined significance is introduced. The proposed novel criteria, definitions, and terminologies should assist in daily practice, as well as in the preparation and conduct of clinical trials. (J Allergy Clin Immunol 2012;130:607-12.)
C1 [Valent, Peter; Sperr, Wolfgang R.] Med Univ Vienna, Dept Med 1, Div Hematol & Hemostaseol, A-1090 Vienna, Austria.
[Klion, Amy D.] NIAID, Eosinophil Pathol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Roufosse, Florence] Univ Libre Brussels, Erasme Hosp, Dept Internal Med, Brussels, Belgium.
[Gotlib, Jason] Stanford Canc Ctr, Div Hematol, Stanford, CA USA.
[Weller, Peter F.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA.
[Hellmann, Andrzej] Med Univ Sch Gdansk, Dept Hematol, Gdansk, Poland.
[Metzgeroth, Georgia; Reiter, Andreas] Univ Heidelberg, Univ Med Mannheim, Med Klin 3, D-6800 Mannheim, Germany.
[Leiferman, Kristin M.; Gleich, Gerald J.] Univ Utah, Hlth Sci Ctr, Dept Dermatol, Salt Lake City, UT USA.
[Arock, Michel] Ecole Normale Super, CNRS, UMR8113, LBPA, Cachan, France.
[Butterfield, Joseph H.] Mayo Clin, Div Allerg Dis, Rochester, MN USA.
[Sotlar, Karl] Univ Munich, Inst Pathol, D-8000 Munich, Germany.
[Vandenberghe, Peter] Univ Hosp Leuven, Ctr Human Genet, Louvain, Belgium.
[Vandenberghe, Peter] Katholieke Univ Leuven, Louvain, Belgium.
[Haferlach, Torsten] MLL Munchner Leukamielabor, Munich, Germany.
[Simon, Hans-Uwe] Univ Bern, Inst Pharmacol, CH-3012 Bern, Switzerland.
[Gleich, Gerald J.] Univ Utah, Hlth Sci Ctr, Dept Med, Salt Lake City, UT 84132 USA.
RP Valent, P (reprint author), Med Univ Vienna, Dept Med 1, Div Hematol & Hemostaseol, Wahringer Gurtel 18-20, A-1090 Vienna, Austria.
EM peter.valent@meduniwien.ac.at
OI Klion, Amy/0000-0002-4986-5326; Vandenberghe, Peter/0000-0003-4719-1935;
Simon, Hans-Uwe/0000-0002-9404-7736
FU Medical University of Vienna; Novartis; Bristol-Myers Squibb; National
Institutes of Health; Mayo Foundation; GlaxoSmithKline; University of
Utah; Ception; Cephalon; Teva; Immune Design
FX Supported by a Research Grant of the Medical University of Vienna.; P.
Valent receives honoraria and research support from Novartis and
Bristol-Myers Squibb. P. F. Weller has consultant arrangements with
GlaxoSmithKline, receives research support from the National Institutes
of Health, and is secretary-treasurer of the International Eosinophil
Society. K. M. Leiferman receives royalties from the Mayo Foundation and
is a scientific advisory member for the National Eczema Association. M.
Arock receives honoraria from Novartis. T. Haferlach is part owner of
the Munich Leukemia Laboratory. A. Reiter has consultant arrangements
with and has received honoraria from Novartis Pharma. G. J. Gleich has
consultant arrangements with GlaxoSmithKline, Ception, Cephalon, Teva,
and Beiersdorf; receives grant support from GlaxoSmithKline, Novartis,
and the University of Utah; receives royalties from Ception, Cephalon,
Teva, and the Mayo Foundation; receives equities from Immune Design; is
on the Board of Directors for the American Partnership for Eosinophilic
Disorders; and has submitted patents for studies of
eosinophil-associated diseases. The rest of the authors declare that
they have no relevant conflicts of interest.
NR 95
TC 111
Z9 120
U1 1
U2 15
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 2012
VL 130
IS 3
BP 607
EP +
DI 10.1016/j.jaci.2012.02.019
PG 15
WC Allergy; Immunology
SC Allergy; Immunology
GA 001LZ
UT WOS:000308463500005
PM 22460074
ER
PT J
AU Sibilano, R
Frossi, B
Suzuki, R
D'Inca, F
Gri, G
Piconese, S
Colombo, MP
Rivera, J
Pucillo, CE
AF Sibilano, Riccardo
Frossi, Barbara
Suzuki, Ryo
D'Inca, Federica
Gri, Giorgia
Piconese, Silvia
Colombo, Mario P.
Rivera, Juan
Pucillo, Carlo E.
TI Modulation of Fc epsilon RI-dependent mast cell response by OX40L via
Fyn, PI3K, and RhoA
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE OX40L; Fyn; PI3K; mast cell; degranulation; anaphylaxis
ID REGULATORY T-CELLS; AFFINITY IGE RECEPTOR; ALLERGIC RESPONSES;
CROSS-TALK; DEGRANULATION; ACTIVATION; KINASE; IMMUNITY; LIGAND;
COSTIMULATION
AB Background: The interaction of mast cells (MCs) with regulatory T cells through the OX40 ligand (OX40L):OX40 axis downregulates Fc epsilon RI-dependent immediate hypersensitivity responses both in vitro and in vivo. Little is known on OX40L-mediated intracellular signaling or on the mechanism by which OX40L engagement suppresses MC degranulation.
Objective: We explored the role of OX40L engagement on IgE/antigen-triggered MCs both in vitro and in vivo. Methods: The soluble form of OX40 molecule was used to selectively trigger OX40L on MCs in vitro and was used to dissect OX40L contribution in an in vivo model of systemic anaphylaxis.
Results: OX40L: OX40 interaction led to the recruitment of C-terminal src kinase into lipid rafts, causing a preferential suppression of Fyn kinase activity and subsequent reduction in the phosphorylation of Gab2, the phosphatidylinositol 3-OH kinase regulatory subunit p85, and Akt, without affecting the Lyn pathway. Dampening of Fyn kinase activity also inhibited RhoA activation and microtubule nucleation, key regulators of MC degranulation. The in vivo administration of a blocking antibody to OX40L in wild-type mice caused enhanced immediate hypersensitivity, whereas the administration of soluble OX40 to regulatory T-cell-depleted or OX40-deficient mice reduced MC degranulation.
Conclusions: The engagement of OX40L selectively suppresses Fyn-initiated signals required for MC degranulation and serves to limit immediate hypersensitivity. Our data suggest that soluble OX40 can restore the aberrant or absent regulatory T-cell activity, revealing a previously unappreciated homeostatic role for OX40L in setting the basal threshold of MC response. (J Allergy Clin Immunol 2012;130:751-60.)
C1 [Sibilano, Riccardo; Frossi, Barbara; D'Inca, Federica; Gri, Giorgia; Pucillo, Carlo E.] Univ Udine, Dept Med & Biol Sci, I-33100 Udine, Italy.
[Suzuki, Ryo; Rivera, Juan] NIAMSD, Immunogenet Mol Lab, NIH, Bethesda, MD 20892 USA.
[Piconese, Silvia; Colombo, Mario P.] Fdn IRCCS Ist Nazl Tumori, Mol Immunol Unit, Dept Expt Oncol & Mol Med, Milan, Italy.
RP Frossi, B (reprint author), Univ Udine, Dept Med & Biol Sci, Ple Kolbe 4, I-33100 Udine, Italy.
EM barbara.frossi@uniud.it
FU Italian Ministry of Health; AIRC (Associazione Italiana Ricerca sul
Cancro); Ministero dell'Istruzione; Universita e Ricerca (PRIN);
Fondazione Compagnia di San Paolo, Turin, Italy; National Institute of
Arthritis and Musculoskeletal and Skin Diseases of the National
Institutes of Health (Bethesda, Md); My First AIRC Grant [8726]
FX Supported by the Italian Ministry of Health, AIRC (Associazione Italiana
Ricerca sul Cancro), Ministero dell'Istruzione, Universita e Ricerca
(PRIN 2009), Fondazione Compagnia di San Paolo, Turin, Italy, and the
Intramural Research Program of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases of the National Institutes of Health
(Bethesda, Md). S.P. was supported by a My First AIRC Grant (8726).
NR 42
TC 11
Z9 11
U1 1
U2 3
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 2012
VL 130
IS 3
BP 751
EP +
DI 10.1016/j.jaci.2012.03.032
PG 12
WC Allergy; Immunology
SC Allergy; Immunology
GA 001LZ
UT WOS:000308463500026
PM 22564682
ER
PT J
AU Hipp, SJ
Steffen-Smith, EA
Patronas, N
Herscovitch, P
Solomon, JM
Bent, RS
Steinberg, SM
Warren, KE
AF Hipp, Sean J.
Steffen-Smith, Emilie A.
Patronas, Nicholas
Herscovitch, Peter
Solomon, Jeffrey M.
Bent, Robyn S.
Steinberg, Seth M.
Warren, Katherine E.
TI Molecular imaging of pediatric brain tumors: comparison of tumor
metabolism using F-18-FDG-PET and MRSI
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Article
DE Pediatric; Brain tumor; F-18-FDG-PET; MR spectroscopy; Metabolism
ID POSITRON-EMISSION-TOMOGRAPHY; MAGNETIC-RESONANCE-SPECTROSCOPY; CNS
TUMORS; GLIOMA; CHILDREN; SURVIVAL; PET; RADIOCHEMOTHERAPY; RECURRENCE;
PREDICTION
AB Magnetic resonance spectroscopic imaging (MRSI) and F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) are non-invasive imaging techniques routinely used to evaluate tumor malignancy in adults with brain tumors. We compared the metabolic activity of pediatric brain tumors using FDG-PET and MRSI. Children (n = 37) diagnosed with a primary brain tumor underwent FDG-PET and MRSI within two weeks of each other. Tumor metabolism was classified as inactive, active or highly active using the maximum choline:N-acetyl-asparate (Cho:NAA) on MRSI and the highest tumor uptake on FDG-PET. A voxel-wise comparison was used to evaluate the area with the greatest abnormal metabolism. Agreement between methods was assessed using the percent agreement and the kappa statistic (kappa). Pediatric brain tumors were metabolically heterogeneous on FDG-PET and MRSI studies. Active tumor metabolism was observed more frequently using MRSI compared to FDG-PET, and agreement in tumor classification was weak (kappa = 0.16, p = 0.12), with 42 % agreement (95 % CI = 25-61 %). Voxel-wise comparison for identifying the area of greatest metabolic activity showed overlap in the majority (62 %) of studies, though exact agreement between techniques was low (29.4 %, 95 % CI = 15.1-47.5 %). These results indicate that FDG-PET and MRSI detect similar but not always identical regions of tumor activity, and there is little agreement in the degree of tumor metabolic activity between the two techniques.
C1 [Hipp, Sean J.; Steffen-Smith, Emilie A.; Bent, Robyn S.; Warren, Katherine E.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Hipp, Sean J.] San Antonio Mil Med Ctr, Dept Pediat, Ft Sam Houston, TX 78234 USA.
[Hipp, Sean J.] Walter Reed Natl Mil Med Ctr, Dept Pediat, Bethesda, MD 20889 USA.
[Hipp, Sean J.] Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA.
[Patronas, Nicholas; Solomon, Jeffrey M.] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
[Herscovitch, Peter] NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA.
[Solomon, Jeffrey M.] Expert Image Anal LLC, Potomac, MD 20854 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Warren, KE (reprint author), NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bldg 10,Room 1-5750,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM warrenk@mail.nih.gov
OI Steffen-Smith, Emilie/0000-0002-4966-3046
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research
FX This work was presented in part at the 2011 ASCO annual meeting in
Chicago, IL. The views expressed in this article are those of the
authors and do not reflect the official policy of the National
Institutes of Health, Department of Army, Department of Defense, or U.S.
Government. Research was supported in part by the Intramural Research
Program of the National Institutes of Health, National Cancer Institute,
Center for Cancer Research.
NR 30
TC 7
Z9 7
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-594X
J9 J NEURO-ONCOL
JI J. Neuro-Oncol.
PD SEP
PY 2012
VL 109
IS 3
BP 521
EP 527
DI 10.1007/s11060-012-0918-0
PG 7
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 001DZ
UT WOS:000308441700009
PM 22760419
ER
PT J
AU Massaro, AN
Chang, T
Kadom, N
Tsuchida, T
Scafidi, J
Glass, P
McCarter, R
Baumgart, S
Vezina, G
Nelson, KB
AF Massaro, An N.
Chang, Taeun
Kadom, Nadja
Tsuchida, Tammy
Scafidi, Joseph
Glass, Penny
McCarter, Robert
Baumgart, Stephen
Vezina, Gilbert
Nelson, Karin B.
TI Biomarkers of Brain Injury in Neonatal Encephalopathy Treated with
Hypothermia
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID NEURON-SPECIFIC ENOLASE; HYPOXIC-ISCHEMIC ENCEPHALOPATHY; WHOLE-BODY
HYPOTHERMIA; RANDOMIZED-CONTROLLED-TRIAL; MYELIN BASIC-PROTEIN; TERM
INFANTS; S100B PROTEIN; BIOCHEMICAL MARKERS; PERINATAL ASPHYXIA;
PROGNOSTIC VALUE
AB Objective To determine if early serum S100B and neuron-specific enolase (NSE) levels are associated with neuro-radiographic and clinical evidence of brain injury in newborns with encephalopathy.
Study design Patients who received therapeutic whole-body hypothermia were prospectively enrolled in this observational study. Serum specimens were collected at 0, 12, 24, and 72 hours of cooling. S100B and NSE levels were measured by enzyme linked immunosorbent assay. Magnetic resonance imaging was performed in surviving infants at 7-10 days of life. Standardized neurologic examination was performed by a child neurologist at 14 days of life. Multiple linear regression analyses were performed to evaluate the association between S100B and NSE levels and unfavorable outcome (death or severe magnetic resonance imaging injury/significant neurologic deficit). Cutoff values were determined by receiver operating curve analysis.
Results Newborns with moderate to severe encephalopathy were enrolled (n = 75). Median pH at presentation was 6.9 (range, 6.5-7.35), and median Apgar scores of 1 at 1 minute, 3 at 5 minutes, and 5 at 10 minutes. NSE and S100B levels were higher in patients with unfavorable outcomes across all time points. These results remained statistically significant after controlling for covariables, including encephalopathy grade at presentation, Apgar score at 5 minutes of life, initial pH, and clinical seizures.
Conclusion Elevated serum S100B and NSE levels measured during hypothermia were associated with neuro-radiographic and clinical evidence of brain injury in encephalopathic newborns. These brain-specific proteins may be useful immediate biomarkers of cerebral injury severity. (J Pediatr 2012;161:434-40).
C1 [Massaro, An N.; Baumgart, Stephen] Childrens Natl Med Ctr, Dept Neonatol, Washington, DC 20010 USA.
[Chang, Taeun; Tsuchida, Tammy; Scafidi, Joseph; Nelson, Karin B.] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA.
[Kadom, Nadja; Vezina, Gilbert] Childrens Natl Med Ctr, Dept Neuroradiol, Washington, DC 20010 USA.
[Glass, Penny] Childrens Natl Med Ctr, Dept Psychiat & Behav Sci, Washington, DC 20010 USA.
[McCarter, Robert] Childrens Natl Med Ctr, Dept Biostat & Informat, Washington, DC 20010 USA.
[Nelson, Karin B.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
RP Massaro, AN (reprint author), Childrens Natl Med Ctr, Dept Neonatol, 111 Michigan Ave NW, Washington, DC 20010 USA.
EM anguyenm@cnmc.org
OI Kadom, Nadja/0000-0002-7073-956X
FU Pediatric Clinical Research Scholars Award [5K12RR17613-05]; Clinical
and Translational Science Institute at Children's National Medical
Center [1KL2RR031987-01]; National Institute of Neurological Disorders
and Stroke [NIH NINDS 1K08NS073793]
FX Supported by the Pediatric Clinical Research Scholars Award
(5K12RR17613-05 to A. M.), the Clinical and Translational Science
Institute at Children's National Medical Center (1KL2RR031987-01 to A.
M.), and the National Institute of Neurological Disorders and Stroke
(NIH NINDS 1K08NS073793 to J.S.). The authors declare no conflicts of
interest.
NR 45
TC 21
Z9 27
U1 1
U2 6
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 2012
VL 161
IS 3
BP 434
EP 440
DI 10.1016/j.jpeds.2012.02.047
PG 7
WC Pediatrics
SC Pediatrics
GA 997CL
UT WOS:000308141700017
PM 22494878
ER
PT J
AU Bliss, JM
Wong, AY
Bhak, G
Laforce-Nesbitt, SS
Taylor, S
Tan, S
Stoll, BJ
Higgins, RD
Shankaran, S
Benjamin, DK
AF Bliss, Joseph M.
Wong, Angela Y.
Bhak, Grace
Laforce-Nesbitt, Sonia S.
Taylor, Sarah
Tan, Sylvia
Stoll, Barbara J.
Higgins, Rosemary D.
Shankaran, Seetha
Benjamin, Daniel K., Jr.
CA Eunice Kennedy Shriver Natl Inst
TI Candida Virulence Properties and Adverse Clinical Outcomes in Neonatal
Candidiasis
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CELL-SURFACE HYDROPHOBICITY; INVASIVE
FUNGAL-INFECTION; BIRTH-WEIGHT INFANTS; RISK-FACTORS; GENE-EXPRESSION;
ALBICANS; PARAPSILOSIS; EPIDEMIOLOGY; ADHESION
AB Objective To determine whether premature infants with invasive Candida infection caused by strains with increased virulence properties have worse clinical outcomes than those infected with less virulent strains.
Study design Clinical isolates were studied from 2 populations of premature infants, those colonized with Candida spp (commensal; n = 27) and those with invasive candidiasis (n = 81). Individual isolates of C albicans and C parapsilosis were tested for virulence in 3 assays: phenotypic switching, adhesion, and cytotoxicity. Invasive isolates were considered to have enhanced virulence if detected at a level > 1 SD above the mean for the commensal isolates in at least one assay. Outcomes of patients with invasive isolates with enhanced virulence were compared with those with invasive isolates lacking enhanced virulence characteristics.
Results Enhanced virulence was detected in 61% of invasive isolates of C albicans and 42% of invasive isolates of C parapsilosis. All C albicans cerebrospinal fluid isolates (n = 6) and 90% of urine isolates (n = 10) had enhanced virulence, compared with 48% of blood isolates (n = 40). Infants with more virulent isolates were younger at the time of positive culture and had higher serum creatinine levels.
Conclusion Individual isolates of Candida species vary in their virulence properties. Strains with higher virulence are associated with certain clinical outcomes. (J Pediatr 2012;161:441-7).
C1 [Bliss, Joseph M.; Laforce-Nesbitt, Sonia S.] Women & Infants Hosp Rhode Isl, Dept Pediat, Providence, RI USA.
[Bliss, Joseph M.; Wong, Angela Y.; Bhak, Grace; Laforce-Nesbitt, Sonia S.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA.
[Taylor, Sarah; Tan, Sylvia] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA.
[Stoll, Barbara J.] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA.
[Stoll, Barbara J.] Childrens Healthcare Atlanta, Atlanta, GA USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Shankaran, Seetha] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
[Benjamin, Daniel K., Jr.] Duke Univ, Dept Pediat, Durham, NC 27706 USA.
RP Bliss, JM (reprint author), Women & Infants Hosp Rhode Isl, Dept Pediat, 101 Dudley St, Providence, RI 02905 USA.
EM jbliss@wihri.org
RI Bliss, Joseph/C-7446-2013
FU National Institutes of Health [M01 RR30, M01 RR32, M01 RR39, M01 RR44,
M01 RR54, M01 RR59, M01 RR70, M01 RR80, M01 RR125, M01 RR633, M01 RR750,
M01 RR997, M01 RR7122, M01 RR8084, UL1 RR24139, UL1 RR24160, UL1
RR25008]; Eunice Kennedy Shriver National Institute of Child Health and
Human Development (NICHD) [U10 HD21364, U10 HD21385, U10 HD21397, U10
HD27851, U10 HD27853, U10 HD27871, U10 HD27880, U10 HD27856, U10
HD27904, U10 HD34216, U10 HD36790, U10 HD40461, U10 HD40492, U10
HD40498, U10 HD40521, U10 HD40689, U10 HD53109, U10 HD53119, U10
HD53089, HD44799]; National Center for Research Resources [RR018728];
National Institute of General Medical Sciences [GM103537]; Thrasher
Research Fund
FX Neonatal Research Network's Candidiasis Study funded by the National
Institutes of Health (M01 RR30, M01 RR32, M01 RR39, M01 RR44, M01 RR54,
M01 RR59, M01 RR70, M01 RR80, M01 RR125, M01 RR633, M01 RR750, M01
RR997, M01 RR7122, M01 RR8084, UL1 RR24139, UL1 RR24160, UL1 RR25008)
and the Eunice Kennedy Shriver National Institute of Child Health and
Human Development (NICHD) (U10 HD21364, U10 HD21385, U10 HD21397, U10
HD27851, U10 HD27853, U10 HD27871, U10 HD27880, U10 HD27856, U10
HD27904, U10 HD34216, U10 HD36790, U10 HD40461, U10 HD40492, U10
HD40498, U10 HD40521, U10 HD40689, U10 HD53109, U10 HD53119, U10
HD53089). J.B. received support from the National Center for Research
Resources (grant RR018728) and the National Institute of General Medical
Sciences (grant GM103537). D.B. received support from the Thrasher
Research Fund and the Eunice Kennedy Shriver National Institute of Child
Health and Human Development (grant HD44799).
NR 32
TC 6
Z9 6
U1 0
U2 5
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 2012
VL 161
IS 3
BP 441
EP +
DI 10.1016/j.jpeds.2012.02.051
PG 9
WC Pediatrics
SC Pediatrics
GA 997CL
UT WOS:000308141700018
PM 22504098
ER
PT J
AU Derauf, C
LaGasse, LL
Smith, LM
Newman, E
Shah, R
Neal, CR
Arria, AM
Huestis, MA
DellaGrotta, S
Dansereau, LM
Lin, H
Lester, BM
AF Derauf, Chris
LaGasse, Linda L.
Smith, Lynne M.
Newman, Elana
Shah, Rizwan
Neal, Charles R.
Arria, Amelia M.
Huestis, Marilyn A.
DellaGrotta, Sheri
Dansereau, Lynne M.
Lin, Hai
Lester, Barry M.
TI Prenatal Methamphetamine Exposure and Inhibitory Control among Young
School-Age Children
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID MATERNAL LIFE-STYLE; COCAINE EXPOSURE; INFANT DEVELOPMENT; COGNITIVE
CONTROL; EFFORTFUL CONTROL; INTRAUTERINE GROWTH; MIDDLE CHILDHOOD; DRUG
EXPOSURE; WHITE-MATTER; ENVIRONMENT
AB Objective To examine the association between prenatal methamphetamine exposure and inhibitory control in 66-month-old children followed since birth in the multicenter, longitudinal Infant Development, Environment, and Lifestyle study.
Study design The sample included 137 children with prenatal methamphetamine exposure and 130 comparison children matched for race, birth weight, maternal education, and type of insurance. Inhibitory control, an executive function related to emotional and cognitive control, was assessed using a computerized Stroop-like task developed for young children. Hierarchical linear modeling tested the relationship between the extent of prenatal methamphetamine exposure (heavy, some, or none) and accuracy and reaction time outcomes, adjusting for prenatal exposure to alcohol, tobacco, and marijuana; age; sex; socioeconomic status; caregiver IQ and psychological symptoms; Child Protective Services report of physical or sexual abuse; and site.
Results In adjusted analyses, heavy prenatal methamphetamine exposure was related to reduced accuracy in both the incongruent and mixed conditions on the Stroop-like task. Caregiver psychological symptoms and Child Protective Services report of physical or sexual abuse were associated with reduced accuracy in the incongruent and mixed consitions and in the incongruent conditions, respectively.
Conclusion Heavy prenatal methamphetamine exposure, along with caregiver psychological distress and child maltreatment, are related to subtle deficits in inhibitory control during the early school-age years. (J Pediatr 2012;161:452-9).
C1 [Derauf, Chris; Neal, Charles R.] Univ Hawaii, Dept Pediat, Honolulu, HI 96822 USA.
[LaGasse, Linda L.; DellaGrotta, Sheri; Dansereau, Lynne M.; Lin, Hai; Lester, Barry M.] Brown Univ, Brown Ctr Study Children Risk, Warren Alpert Med Sch, Providence, RI 02912 USA.
[LaGasse, Linda L.; DellaGrotta, Sheri; Dansereau, Lynne M.; Lin, Hai; Lester, Barry M.] Brown Univ, Women & Infants Hosp, Providence, RI USA.
[Smith, Lynne M.] Harbor UCLA Med Ctr, Dept Pediat, LABioMed Inst, Los Angeles, CA USA.
[Smith, Lynne M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Newman, Elana] Univ Tulsa, Dept Psychol, Tulsa, OK 74104 USA.
[Shah, Rizwan] Blank Hosp Reg Child Protect Ctr Iowa Hlth, Des Moines, IA USA.
[Arria, Amelia M.] Univ Maryland, Ctr Young Adult Hlth & Dev, Sch Publ Hlth, Family Sci Dept, College Pk, MD 20742 USA.
[Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD USA.
RP Derauf, C (reprint author), Mayo Clin, Dept Pediat & Adolescent Med, 200 1st St SW, Rochester, MN 55905 USA.
EM derauf.donald@mayo.edu
OI Arria, Amelia/0000-0002-6360-9265
FU National Institutes on Drug Abuse [2R01DA014948, 1K23DA020801]; National
Center for Research Resources [5P20RR11091, 3M01RR00425]
FX Supported by the National Institutes on Drug Abuse (grants 2R01DA014948
[to B.L.] and 1K23DA020801 [to C.D.]) and by the National Center for
Research Resources (grants 5P20RR11091 and 3M01RR00425). The authors
declare no conflicts of interest.
NR 52
TC 13
Z9 13
U1 5
U2 20
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 2012
VL 161
IS 3
BP 452
EP 459
DI 10.1016/j.jpeds.2012.02.002
PG 8
WC Pediatrics
SC Pediatrics
GA 997CL
UT WOS:000308141700020
PM 22424953
ER
PT J
AU Bang, JK
Song, YS
Park, JE
Murugan, RN
Ahn, M
Lee, KS
AF Bang, J. K.
Song, Y. S.
Park, J. E.
Murugan, R. N.
Ahn, M.
Lee, K. S.
TI Synthesis of Peptide Mimetic Inhibitors Targeting Polo-Box Domain of
Polo-like Kinase 1
SO JOURNAL OF PEPTIDE SCIENCE
LA English
DT Meeting Abstract
C1 [Bang, J. K.; Murugan, R. N.; Ahn, M.] Korea Basic Sci Inst, Div Magnet Resonance Res, Chungbuk 363883, South Korea.
[Song, Y. S.] Chosun Univ, Sch Med, Dept Cellular & Mol Med, Kwangju 501759, South Korea.
[Park, J. E.; Lee, K. S.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1075-2617
J9 J PEPT SCI
JI J. Pept. Sci.
PD SEP
PY 2012
VL 18
SU 1
BP S192
EP S193
PG 2
WC Biochemistry & Molecular Biology; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 996MC
UT WOS:000308091500486
ER
PT J
AU Park, JE
Liu, F
Qian, WJ
Lim, D
Bang, JK
Yaffe, MB
Burke, TR
Lee, KS
AF Park, J-E.
Liu, F.
Qian, W-J.
Lim, D.
Bang, J. K.
Yaffe, M. B.
Burke, T. R., Jr.
Lee, K. S.
TI Peptide-derived inhibitors targeting polo-like kinase 1 for anti-cancer
therapy
SO JOURNAL OF PEPTIDE SCIENCE
LA English
DT Meeting Abstract
C1 [Park, J-E.; Lee, K. S.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
[Liu, F.; Qian, W-J.; Burke, T. R., Jr.] NCI, Biol Chem Lab, Frederick Natl Lab, Frederick, MD 21702 USA.
[Lim, D.; Yaffe, M. B.] MIT, Dept Biol, Cambridge, MA 02139 USA.
[Bang, J. K.] Korea Basic Sci Inst, Ochang 363883, Chung Buk, South Korea.
NR 3
TC 0
Z9 0
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1075-2617
J9 J PEPT SCI
JI J. Pept. Sci.
PD SEP
PY 2012
VL 18
SU 1
BP S51
EP S51
PG 1
WC Biochemistry & Molecular Biology; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 996MC
UT WOS:000308091500091
ER
PT J
AU Veiga, AS
Sinthuvanich, C
Gaspar, D
Franquelim, HG
Castanho, M
Schneider, JP
AF Veiga, A. S.
Sinthuvanich, C.
Gaspar, D.
Franquelim, H. G.
Castanho, M.
Schneider, J. P.
TI Arginine-rich self-assembling peptides form injectable antibacterial
hydrogels
SO JOURNAL OF PEPTIDE SCIENCE
LA English
DT Meeting Abstract
C1 [Veiga, A. S.; Sinthuvanich, C.; Schneider, J. P.] NCI, Biol Chem Lab, NIH, Frederick, MD 21702 USA.
[Veiga, A. S.; Gaspar, D.; Franquelim, H. G.; Castanho, M.] Univ Lisbon, Fac Med, Inst Mol Med, P-1649028 Lisbon, Portugal.
[Sinthuvanich, C.] Univ Delaware, Dept Chem & Biochem, Newark, DE 19716 USA.
NR 0
TC 1
Z9 1
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1075-2617
J9 J PEPT SCI
JI J. Pept. Sci.
PD SEP
PY 2012
VL 18
SU 1
BP S112
EP S112
PG 1
WC Biochemistry & Molecular Biology; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 996MC
UT WOS:000308091500257
ER
PT J
AU Carneiro-Lobo, TC
Schaffner, F
Disse, J
Ostergaard, H
Francischetti, IMB
Monteiro, RQ
Ruf, W
AF Carneiro-Lobo, T. C.
Schaffner, F.
Disse, J.
Ostergaard, H.
Francischetti, I. M. B.
Monteiro, R. Q.
Ruf, W.
TI The tick-derived inhibitor Ixolaris prevents tissue factor signaling on
tumor cells
SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS
LA English
DT Article
DE protease activated receptor; angiogenesis; breast cancer
ID FACTOR PATHWAY INHIBITOR; BLOOD-COAGULATION FACTOR; HEPARIN-BINDING
EXOSITE; FACTOR-VIIA; FACTOR EXPRESSION; FACTOR-XA; PANCREATIC-CANCER;
ENDOTHELIAL-CELLS; CRYSTAL-STRUCTURE; MDA-MB-231 CELLS
AB Background: Tissue factor (TF) is frequently overexpressed in cancer cells and correlated with more aggressive tumor phenotypes and poor prognosis. In addition to promoting coagulation-dependent metastasis and cancer-associated thrombosis, tumor cell-expressed TF mediates direct cell signaling involving the protease-activated receptor (PAR) 2. Ixolaris is a tick-derived inhibitor of the TFfactor (F)VIIaXa coagulation initiation complex which blocks primary tumor growth and angiogenesis in glioblastoma and melanoma models. Methods: In this study we address the anti-tumor effects of Ixolaris in TFVIIaPAR2 signaling-dependent breast cancer models, a xenograft model of highly aggressive human MDA-MB-231mfp cells and a syngeneic model of PAR2-deficient and replete PyMT mouse mammary carcinoma cells. Results: Ixolaris potently inhibited the procoagulant activity of human MDA-MB-231mfp or murine PyMT breast cancer cells. Ixolaris blocked signaling by the ternary TFFVIIaFXa complex, and, surprisingly, at higher concentrations also the binary TFFVIIa complex on MDA-MB-231 cells. We show that Ixolaris interacts with certain residues in the human VIIa protease domain that are involved in PAR2 cleavage. In contrast to human VIIa, Ixolaris was a poor inhibitor of murine TFFVIIa signaling and did not attenuate PAR2-dependent tumor growth in a syngeneic mouse model of breast cancer progression. Conclusion: These data show that Ixolaris inhibits PAR2 cleavage specifically by human TF signaling complexes and suggest that Ixolaris may block tumor growth of human cell models with ectopic FVIIa expression through inhibition of direct TFFVIIaPAR2 signaling as well as its anticoagulant activity.
C1 [Carneiro-Lobo, T. C.; Schaffner, F.; Disse, J.; Ruf, W.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Carneiro-Lobo, T. C.; Monteiro, R. Q.] Univ Fed Rio de Janeiro, Inst Bioquim Med, Rio De Janeiro, Brazil.
[Disse, J.; Ostergaard, H.] Novo Nordisk AS, DK-2760 Malov, Denmark.
[Francischetti, I. M. B.] NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
RP Ruf, W (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, SP258, La Jolla, CA 92037 USA.
EM ruf@scripps.edu
RI Inbeb, Inct/K-2317-2013; Monteiro, Robson/B-8007-2014
FU NIH [HL-60742]; Brazilian funding agency Conselho Nacional de
Desenvolvimento Cientifico e Tecnologico; Novo Nordisk; Intramural
Research Program of the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases and National Institutes of
Health
FX We would like to thank P. Tejada and J. Freire e Souza for technical
assistance. This work was supported by NIH grant HL-60742 (W. R.), a
fellowship from the Brazilian funding agency Conselho Nacional de
Desenvolvimento Cientifico e Tecnologico (T. C. C.-L.) and by Novo
Nordisk (J.D.). This work was supported by the Intramural Research
Program of the Division of Intramural Research, National Institute of
Allergy and Infectious Diseases and National Institutes of Health.
Because I. M. B. Francischetti is a government employee and this is a
government work, the work is in the public domain in the United States.
NR 47
TC 11
Z9 13
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1538-7933
J9 J THROMB HAEMOST
JI J. Thromb. Haemost.
PD SEP
PY 2012
VL 10
IS 9
BP 1849
EP 1858
DI 10.1111/j.1538-7836.2012.04864.x
PG 10
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 999FI
UT WOS:000308294400017
PM 22823596
ER
PT J
AU Charoenpanich, A
Wall, ME
Tucker, CJ
Andrews, DMK
Lalush, DS
Loboa, EG
AF Charoenpanich, A.
Wall, M. E.
Tucker, C. J.
Andrews, D. M. K.
Lalush, D. S.
Loboa, E. G.
TI Microarray analysis of human MSC in 3D collagen culture: 10% uniaxial
cyclic tensile strain upregulates genes associated with musculoskeletal
and cardiovascular development
SO JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE
LA English
DT Meeting Abstract
C1 NC State Univ, Raleigh, NC USA.
Univ N Carolina, Chapel Hill, NC USA.
NIEHS, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1932-6254
J9 J TISSUE ENG REGEN M
JI J. Tissue Eng. Regen. Med.
PD SEP
PY 2012
VL 6
SU 1
SI SI
BP 343
EP 344
PG 2
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology; Engineering, Biomedical
SC Cell Biology; Biotechnology & Applied Microbiology; Engineering
GA 999LG
UT WOS:000308313003080
ER
PT J
AU Rosano, C
Bennett, DA
Newman, AB
Venkatraman, V
Yaffe, K
Harris, T
Kritchevsky, S
Aizenstein, HJ
AF Rosano, Caterina
Bennett, David A.
Newman, Anne B.
Venkatraman, Vijay
Yaffe, Kristine
Harris, Tamara
Kritchevsky, Stephen
Aizenstein, Howard J.
TI Patterns of Focal Gray Matter Atrophy Are Associated With Bradykinesia
and Gait Disturbances in Older Adults
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Bradykinesia; Gait disturbances; Brain MRI
ID MILD PARKINSONIAN SIGNS; MAGNETIC-RESONANCE; BRAIN ATROPHY;
DIFFERENTIAL-DIAGNOSIS; COMMUNITY POPULATION; IMAGING TECHNIQUES;
BODY-COMPOSITION; MR-IMAGES; DISEASE; HEALTH
AB Identify the neuroimaging correlates of parkinsonian signs in older adults living in the community.
Magnetic resonance imaging was obtained in 307 adults (82.9 years, 55% women, 39% blacks) concurrently with the Unified Parkinson Disease Rating scale-motor part. Magnetic resonance imaging measures included volume of whole-brain white matter hyperintensities and of gray matter for primary sensorimotor, supplementary motor, medial temporal areas, cerebellum, prefronto-parietal cortex, and basal ganglia.
About 25% of the participants had bradykinesia, 26% had gait disturbances, and 12% had tremor. Compared with those without, adults with any one of these signs were older, walked more slowly, had worse scores on tests of cognition, mood and processing speed, and higher white matter hyperintensities volume (all p < .002). Gray matter volume of primary sensorimotor area was associated with bradykinesia (standardized odds ratio [95% confidence interval]: 0.46 [0.31, 0.68], p < .0001), and gray matter volume of medial temporal area was associated with gait disturbances (0.56 [0.42, 0.83], p < .0001), independent of white matter hyperintensities volume and age. Further adjustment for measures of muscle strength, cardiovascular health factors, cognition, processing speed, and mood or for gait speed did not substantially change these results.
Atrophy within primary sensorimotor and medial temporal areas might be important for development of bradykinesia and of gait disturbances in community-dwelling elderly adults. The pathways underlying these associations may not include changes in white matter hyperintensities volume, cognition, information processing speed, mood, or gait speed.
C1 [Rosano, Caterina; Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA.
[Bennett, David A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.
[Venkatraman, Vijay] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15213 USA.
[Yaffe, Kristine] UCSF Sch Med, Dept Psychiat, San Francisco, CA USA.
[Harris, Tamara] NIA, Geriatr Epidemiol Sect, Bethesda, MD 20892 USA.
[Kritchevsky, Stephen] Wake Forest Sch Med, Dept Geriatr & Gerontol, Winston Salem, NC USA.
[Aizenstein, Howard J.] Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA 15213 USA.
RP Rosano, C (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, 130 N Bellefield St,Room 512, Pittsburgh, PA 15213 USA.
EM rosanoc@edc.pitt.edu
RI Newman, Anne/C-6408-2013;
OI Newman, Anne/0000-0002-0106-1150; Rosano, Caterina/0000-0002-0909-1506;
Rosano, Caterina/0000-0002-4271-6010; Kritchevsky,
Stephen/0000-0003-3336-6781
FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106]; NIA [R01-AG028050]; National Institute of Nursing
Research [R01-NR012459, R01 MH076079, P30 AG024827-06 1, R01
AG029232-01]; Intramural Research Program of the NIH, National Institute
on Aging
FX This research was supported by National Institute on Aging (NIA)
contracts N01-AG-6-2101; N01-AG-6-2103, and N01-AG-6-2106; NIA grant
R01-AG028050; National Institute of Nursing Research grant R01-NR012459,
R01 MH076079, P30 AG024827-06 1, and R01 AG029232-01; and in part by the
Intramural Research Program of the NIH, National Institute on Aging.
NR 39
TC 16
Z9 16
U1 0
U2 3
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 2012
VL 67
IS 9
BP 957
EP 962
DI 10.1093/gerona/glr262
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 998LP
UT WOS:000308240900005
PM 22367436
ER
PT J
AU Gottesman, RF
Sojkova, J
Beason-Held, LL
An, Y
Longo, DL
Ferrucci, L
Resnick, SM
AF Gottesman, Rebecca F.
Sojkova, Jitka
Beason-Held, Lori L.
An, Yang
Longo, Dan L.
Ferrucci, Luigi
Resnick, Susan M.
TI Patterns of Regional Cerebral Blood Flow Associated With Low Hemoglobin
in the Baltimore Longitudinal Study of Aging
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Cerebral blood flow; Anemia; PET; Aging
ID POSITRON-EMISSION-TOMOGRAPHY; DWELLING OLDER WOMEN; ANEMIA; BRAIN;
HEMODILUTION; HEMATOCRIT; METABOLISM; TRANSFUSION; DELIVERY; HYPOXIA
AB Anemia has been associated with elevated cerebral blood flow (CBF) in animal models and certain clinical conditions (eg, renal disease), but whether hemoglobin level variations across a relatively normal range are associated with local or diffuse CBF changes is unclear. We investigated whether lower hemoglobin is associated with regional increases in relative CBF in older individuals, and if these increases occur in watershed regions.
Seventy-four older nondemented adults underwent serial O-15 water positron emission tomography scans. Voxel-based analysis was used to investigate regional relative CBF patterns in association with hemoglobin level and in individuals with and without anemia. Analyses of cross-sectional relations between regional CBF and anemia were performed separately at two time points, 2 years apart, to identify replicable patterns of associations.
Restricting results to associations replicated across two cross-sectional analyses, lower hemoglobin was associated with higher relative CBF within the middle/inferior frontal, occipital, precuneus, and cerebellar regions. In addition, individuals with anemia (n = 15) showed higher relative CBF in superior frontal, middle temporal, hippocampal, and gyrus rectus regions than those without anemia. In some regions (right superior temporal gyrus, left inferior frontal gyrus, midline cuneus, and right precuneus); however, lower hemoglobin was associated with lower relative CBF.
In nondemented individuals, lower hemoglobin is associated with elevated relative CBF in specific cortical areas but reduced CBF in other areas. Whether this association between anemia and CBF in the absence of chronic diseases and in a normal physiologic range is related to clinical endpoints warrants further study.
C1 [Gottesman, Rebecca F.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA.
[Sojkova, Jitka] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21287 USA.
[Sojkova, Jitka; Beason-Held, Lori L.; An, Yang; Resnick, Susan M.] NIA, Lab Behav Res, Baltimore, MD 21224 USA.
[Longo, Dan L.] NIA, Lab Mol Biol & Immunol, Baltimore, MD 21224 USA.
[Ferrucci, Luigi] NIA, Clin Res Branch, Intramural Res Program, Baltimore, MD 21224 USA.
RP Gottesman, RF (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurol, Meyer 6-113,600 N Wolfe St, Baltimore, MD 21287 USA.
EM rgottesm@jhmi.edu
FU Intramural Research Program of the National Institutes of Health,
National Institute on Aging; [N01-AG-32124]
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health, National Institute on Aging and by
Research and Development Contract N01-AG-32124.
NR 25
TC 5
Z9 6
U1 1
U2 2
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 2012
VL 67
IS 9
BP 963
EP 969
DI 10.1093/gerona/gls121
PG 7
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 998LP
UT WOS:000308240900006
PM 22552368
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, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA.
[Gipson, Chester] USDA, APHIS, AC, Washington, DC USA.
RP Brown, P (reprint author), NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA.
NR 4
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0093-7355
J9 LAB ANIMAL
JI Lab Anim.
PD SEP
PY 2012
VL 41
IS 9
BP 251
EP 251
PG 1
WC Veterinary Sciences
SC Veterinary Sciences
GA 998XY
UT WOS:000308274900016
PM 22914027
ER
PT J
AU Gaudet, MM
Sherman, ME
Thun, MJ
AF Gaudet, Mia M.
Sherman, Mark E.
Thun, Michael J.
TI Learning from disease heterogeneity
SO LANCET ONCOLOGY
LA English
DT Editorial Material
ID OVARIAN-CANCER; STAGE
C1 [Gaudet, Mia M.; Thun, Michael J.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30316 USA.
[Sherman, Mark E.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Biomarkers, Bethesda, MD 20892 USA.
RP Gaudet, MM (reprint author), Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30316 USA.
EM michael.thun@cancer.org
NR 11
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
J9 LANCET ONCOL
JI Lancet Oncol.
PD SEP
PY 2012
VL 13
IS 9
BP 862
EP 863
DI 10.1016/S1470-2045(12)70365-0
PG 3
WC Oncology
SC Oncology
GA 000XZ
UT WOS:000308425600010
PM 22863524
ER
PT J
AU Mattano, LA
Devidas, M
Nachman, JB
Sather, HN
Hunger, SP
Steinherz, PG
Gaynon, PS
Seibel, NL
AF Mattano, Leonard A., Jr.
Devidas, Meenakshi
Nachman, James B.
Sather, Harland N.
Hunger, Stephen P.
Steinherz, Peter G.
Gaynon, Paul S.
Seibel, Nita L.
CA Children's Oncology Grp
TI Effect of alternate-week versus continuous dexamethasone scheduling on
the risk of osteonecrosis in paediatric patients with acute
lymphoblastic leukaemia: results from the CCG-1961 randomised cohort
trial
SO LANCET ONCOLOGY
LA English
DT Article
ID CHILDRENS CANCER GROUP; GLUCOCORTICOID-INDUCED OSTEONECROSIS; FAT-CELL
ENLARGEMENT; AVASCULAR NECROSIS; ADOLESCENTS; THERAPY; COMPLICATION;
CHEMOTHERAPY; SURVIVAL; MODEL
AB Background Acute lymphoblastic leukaemia (ALL) is curable in more than 80% of children and adolescents who exhibit high-risk features. However, treatments are associated with symptomatic osteonecrosis that disproportionately affects adolescents. Based on the findings from the CCG-1882 trial, the CCG-1961 trial was designed to assess whether dexamethasone dose modification would reduce the risk of osteonecrosis. We therefore compared use of continuous versus alternate-week dexamethasone within standard and intensified post-induction treatments.
Methods In the CCG-1961 trial, a multicohort cooperative group trial, 2056 patients (aged 1-21 years) with newly diagnosed high-risk ALL (age >= 10 years, white blood cell count >= 50x10(9) per L, or both) were recruited. To address osteonecrosis, a novel alternate-week schedule of dexamethasone (10 mg/m(2) per day on days 0-6 and 14-20) was compared with standard continuous dexamethasone (10 mg/m(2) per day on days 0-20) in computer-generated randomised regimens with permuted blocks within double or single delayed intensification phases, respectively. Masking was not possible because of the differences in the treatments. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00002812.
Findings Symptomatic osteonecrosis was diagnosed in 143 patients at 377 confirmed skeletal sites, resulting in 139 surgeries. In patients aged 1-21 years, the overall cumulative incidence of osteonecrosis at 5 years was 7.7% (SE 0.9), correlating with age at ALL diagnosis (1-9 years, 1.0% [0.5]; 10-15 years, 9.9% [1.5], hazard ratio 10.4 [4.8-22.5]; 16-21 years, 20.0% [4.3], 22.2 [10.0-49.3]; p<0.0001) and sex of the patients aged 10-21 years (girls 15.7% [2.5] vs boys 9.3% [1.7], 1.7 [1.2-2.4]; p=0.001). For patients aged 10 years and older with a rapid response to induction treatment, the use of alternate-week dexamethasone during phases of delayed intensification significantly reduced osteonecrosis incidence compared with continuous dexamethasone (8.7% [2.1] vs 17.0% [2.9], 2.1 [1.4-3.1]; p=0.0005), especially in those aged 16 years and older (11.3% [5.3] vs 37.5% [11.0], p=0.0003; girls 17.2% [8.1] vs 43.9% [14.1], p=0.05; boys 7.7% [5.9] vs 34.6% [11.6], p=0.0014).
Interpretation Alternate-week dexamethasone during delayed intensification phases, a simple dose modification, reduces the risk of osteonecrosis in children and adolescents given intensified treatment for high-risk ALL. Its use is being evaluated in children with standard risk ALL.
C1 [Mattano, Leonard A., Jr.] Michigan State Univ, Kalamazoo Ctr Med Studies, Coll Human Med, Kalamazoo, MI 49008 USA.
[Devidas, Meenakshi] Univ Florida, Coll Med Publ Hlth & Hlth Profess, Dept Biostat, Gainesville, FL USA.
[Devidas, Meenakshi] Univ Florida, Coll Med Publ Hlth & Hlth Profess, Childrens Oncol Grp, Gainesville, FL USA.
[Nachman, James B.] Univ Chicago, Dept Pediat, Sect Hematol & Oncol, Chicago, IL 60637 USA.
[Sather, Harland N.] Childrens Oncol Grp, Arcadia, CA USA.
[Hunger, Stephen P.] Univ Colorado, Sch Med, Dept Pediat, Sect Hematol Oncol & Bone Marrow Transplantat, Aurora, CO USA.
[Steinherz, Peter G.] Cornell Univ, Weill Med Coll, Dept Pediat, New York, NY 10021 USA.
[Steinherz, Peter G.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Gaynon, Paul S.] Univ So Calif, Dept Pediat, Div Hematol Oncol, Childrens Hosp Los Angeles, Los Angeles, CA 90089 USA.
[Seibel, Nita L.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Mattano, LA (reprint author), Michigan State Univ, Kalamazoo Ctr Med Studies, Coll Human Med, 1000 Oakland Dr, Kalamazoo, MI 49008 USA.
EM mattano@umich.edu
FU US National Cancer Institute at the National Institutes of Health; CTEP
of the National Cancer Institute at the National Institutes of Health,
Bethesda, MD, USA; National Cancer Institute, National Institutes of
Health [CA98543, CA13539]; Statistics and Data Center, National Cancer
Institute, National Institutes of Health [U10 CA98413]; COG
FX US National Cancer Institute at the National Institutes of Health.; This
report is dedicated to the memory of James B Nachman (1948-2011), an
exemplary healer, learner, teacher, humanitarian, and friend. We thank
William L Carroll and Michael E Trigg for providing insightful and
stalwart leadership in the COG ALL research strategy. Funding for this
study was derived from grants awarded to the Children's Cancer Group and
the COG from the CTEP of the National Cancer Institute at the National
Institutes of Health, Bethesda, MD, USA. Research is supported by the
chair's grant CA98543, Statistics and Data Center grant U10 CA98413, and
grant CA13539 of the COG from the National Cancer Institute, National
Institutes of Health. A complete listing of grant support for research
undertaken by CCG and POG before initiation of the COG grant in 2003 is
available online. The content is solely the responsibility of the
authors and does not necessarily represent the official views of the
National Cancer Institute or the National Institutes of Health.
NR 30
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U1 0
U2 4
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 2012
VL 13
IS 9
BP 906
EP 915
DI 10.1016/S1470-2045(12)70274-7
PG 10
WC Oncology
SC Oncology
GA 000XZ
UT WOS:000308425600018
PM 22901620
ER
PT J
AU Beral, V
Gaitskell, K
Hermon, C
Moser, K
Reeves, G
Peto, R
Brinton, L
Marchbanks, P
Negri, E
Ness, R
Peeters, PHM
Vessey, M
Calle, EE
Gapstur, SM
Patel, AV
Dal Maso, L
Talamini, R
Chetrit, A
Hirsh-Yechezkel, G
Lubin, F
Sadetzki, S
Banks, E
Beral, V
Bull, D
Callaghan, K
Crossley, B
Gaitskell, K
Goodill, A
Green, J
Hermon, C
Key, T
Moser, K
Reeves, G
Sitas, F
Collins, R
Doll, R
Peto, R
Gonzalez, A
Lee, N
Marchbanks, P
Ory, HW
Peterson, HB
Wingo, PA
Martin, N
Pardthaisong, T
Silpisornkosol, S
Theetranont, C
Boosiri, B
Chutivongse, S
Jimakorn, P
Virutamasen, P
Wongsrichanalai, C
Tjonneland, A
Titus-Ernstoff, L
Byers, T
Rohan, T
Mosgaard, BJ
Vessey, M
Yeates, D
Freudenheim, JL
Chang-Claude, J
Kaaks, R
Anderson, KE
Folsom, A
Robien, K
Hampton, J
Newcomb, PA
Rossing, MA
Thomas, DB
Weiss, NS
Riboli, E
Clavel-Chapelon, F
Cramer, D
Hankinson, SE
Tworoger, SS
Franceschi, S
La Vecchia, C
Negri, E
Adami, HO
Magnusson, C
Riman, T
Weiderpass, E
Wolk, A
Schouten, LJ
van den Brandt, PA
Chantarakul, N
Koetsawang, S
Rachawat, D
Palli, D
Black, A
Brinton, LA
Freedman, DM
Hartge, P
Hsing, AW
Lacey, JV
Hoover, RN
Schairer, C
Urban, M
Graff-Iversen, S
Selmer, R
Bain, CJ
Green, AC
Purdie, DM
Siskind, V
Webb, PM
Moysich, K
McCann, SE
Hannaford, P
Kay, C
Binns, CW
Lee, AH
Zhang, M
Ness, RB
Nasca, P
Coogan, PF
Palmer, JR
Rosenberg, L
Kelsey, J
Paffenbarger, R
Whittemore, A
Katsouyanni, K
Trichopoulou, A
Trichopoulos, D
Tzonou, A
Dabancens, A
Martinez, L
Molina, R
Salas, O
Goodman, MT
Lurie, G
Carney, ME
Wilkens, LR
Hartman, L
Manjer, J
Olsson, H
Grisso, JA
Morgan, M
Wheeler, JE
Bunker, CH
Edwards, RP
Modugno, F
Peeters, PHM
Casagrande, J
Pike, MC
Ross, RK
Wu, AH
Miller, AB
Kumle, M
Gram, IT
Lund, E
McGowan, L
Shu, XO
Zheng, W
Farley, TMM
Holck, S
Meirik, O
Risch, HA
AF Beral, V.
Gaitskell, K.
Hermon, C.
Moser, K.
Reeves, G.
Peto, R.
Brinton, L.
Marchbanks, P.
Negri, E.
Ness, R.
Peeters, P. H. M.
Vessey, M.
Calle, E. E.
Gapstur, S. M.
Patel, A. V.
Dal Maso, L.
Talamini, R.
Chetrit, A.
Hirsh-Yechezkel, G.
Lubin, F.
Sadetzki, S.
Banks, E.
Beral, V.
Bull, D.
Callaghan, K.
Crossley, B.
Gaitskell, K.
Goodill, A.
Green, J.
Hermon, C.
Key, T.
Moser, K.
Reeves, G.
Sitas, F.
Collins, R.
Doll, R.
Peto, R.
Gonzalez, A.
Lee, N.
Marchbanks, P.
Ory, H. W.
Peterson, H. B.
Wingo, P. A.
Martin, N.
Pardthaisong, T.
Silpisornkosol, S.
Theetranont, C.
Boosiri, B.
Chutivongse, S.
Jimakorn, P.
Virutamasen, P.
Wongsrichanalai, C.
Tjonneland, A.
Titus-Ernstoff, L.
Byers, T.
Rohan, T.
Mosgaard, B. J.
Vessey, M.
Yeates, D.
Freudenheim, J. L.
Chang-Claude, J.
Kaaks, R.
Anderson, K. E.
Folsom, A.
Robien, K.
Hampton, J.
Newcomb, P. A.
Rossing, M. A.
Thomas, D. B.
Weiss, N. S.
Riboli, E.
Clavel-Chapelon, F.
Cramer, D.
Hankinson, S. E.
Tworoger, S. S.
Franceschi, S.
La Vecchia, C.
Negri, E.
Adami, H. O.
Magnusson, C.
Riman, T.
Weiderpass, E.
Wolk, A.
Schouten, L. J.
van den Brandt, P. A.
Chantarakul, N.
Koetsawang, S.
Rachawat, D.
Palli, D.
Black, A.
Brinton, L. A.
Freedman, D. M.
Hartge, P.
Hsing, A. W.
Lacey, J. V., Jr.
Hoover, R. N.
Schairer, C.
Urban, M.
Graff-Iversen, S.
Selmer, R.
Bain, C. J.
Green, A. C.
Purdie, D. M.
Siskind, V.
Webb, P. M.
Moysich, K.
McCann, S. E.
Hannaford, P.
Kay, C.
Binns, C. W.
Lee, A. H.
Zhang, M.
Ness, R. B.
Nasca, P.
Coogan, P. F.
Palmer, J. R.
Rosenberg, L.
Kelsey, J.
Paffenbarger, R.
Whittemore, A.
Katsouyanni, K.
Trichopoulou, A.
Trichopoulos, D.
Tzonou, A.
Dabancens, A.
Martinez, L.
Molina, R.
Salas, O.
Goodman, M. T.
Lurie, G.
Carney, M. E.
Wilkens, L. R.
Hartman, L.
Manjer, J.
Olsson, H.
Grisso, J. A.
Morgan, M.
Wheeler, J. E.
Bunker, C. H.
Edwards, R. P.
Modugno, F.
Peeters, P. H. M.
Casagrande, J.
Pike, M. C.
Ross, R. K.
Wu, A. H.
Miller, A. B.
Kumle, M.
Gram, I. T.
Lund, E.
McGowan, L.
Shu, X. O.
Zheng, W.
Farley, T. M. M.
Holck, S.
Meirik, O.
Risch, H. A.
CA Collaborative Grp Epidemiological
Natl Israeli Study Ovarian Canc
Nurses Hlth Study
TI Ovarian cancer and smoking: individual participant meta-analysis
including 28 114 women with ovarian cancer from 51 epidemiological
studies
SO LANCET ONCOLOGY
LA English
DT Article
ID BODY-MASS INDEX; ORAL-CONTRACEPTIVE USE; EPITHELIAL OVARIAN;
CIGARETTE-SMOKING; PROSPECTIVE COHORT; UNITED-STATES; RISK-FACTORS;
ANTHROPOMETRIC MEASUREMENTS; HORMONAL FACTORS; TOBACCO SMOKING
AB Background Smoking has been linked to mucinous ovarian cancer, but its effects on other ovarian cancer subtypes and on overall ovarian cancer risk are unclear, and the findings from most studies with relevant data are unpublished. To assess these associations, we review the published and unpublished evidence.
Methods Eligible epidemiological studies were identified by electronic searches, review articles, and discussions with colleagues. Individual participant data for 28 114 women with and 94 942 without ovarian cancer from 51 epidemiological studies were analysed centrally, yielding adjusted relative risks (RRs) of ovarian cancer in smokers compared with never smokers.
Findings After exclusion of studies with hospital controls, in which smoking could have affected recruitment, overall ovarian cancer incidence was only slightly increased in current smokers compared with women who had never smoked (RR 1.06, 95% CI 1.01-1.11, p=0.01). Of 17 641 epithelial cancers with specified histology, 2314 (13%) were mucinous, 2360 (13%) endometrioid, 969 (5%) clear-cell, and 9086 (52%) serous. Smoking-related risks varied substantially across these subtypes (p(heterogeneity)<0.0001). For mucinous cancers, incidence was increased in current versus never smokers (1.79, 95% CI 1.60-2.00, p<0.0001), but the increase was mainly in borderline malignant rather than in fully malignant tumours (2.25, 95% CI 1.91-2.65 vs 1.49, 1.28-1.73; p(heterogeneity)=0.01; almost half the mucinous tumours were only borderline malignant). Both endometrioid (0.81, 95% CI 0.72-0.92, p=0.001) and clear-cell ovarian cancer risks (0.80, 95% CI 0.65-0.97, p=0.03) were reduced in current smokers, and there was no significant association for serous ovarian cancers (0.99, 95% CI 0.93-1.06, p=0.8). These associations did not vary significantly by 13 sociodemographic and personal characteristics of women including their body-mass index, parity, and use of alcohol, oral contraceptives, and menopausal hormone therapy.
Interpretation The excess of mucinous ovarian cancers in smokers, which is mainly of tumours of borderline malignancy, is roughly counterbalanced by the deficit of endometrioid and clear-cell ovarian cancers. The substantial variation in smoking-related risks by tumour subtype is important for understanding ovarian carcinogenesis.
C1 [Beral, V.] Univ Oxford, Collaborat Grp Epidemiol Studies Ovarian Canc, Canc Epidemiol Unit, Oxford OX3 7LF, England.
[Peto, R.] Univ Oxford, CR UK MRC BHF Clin Trial Serv Unit, Oxford OX3 7LF, England.
[Peto, R.] Univ Oxford, Epidemiol Studies Unit, Oxford OX3 7LF, England.
[Brinton, L.] NCI, Bethesda, MD 20892 USA.
[Marchbanks, P.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Negri, E.] Univ Milan, Ist Ric Farmacol Mario Negri, Milan, Italy.
[Ness, R.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA.
[Peeters, P. H. M.] Univ Med Ctr Utrecht, Utrecht, Netherlands.
[Vessey, M.] Univ Oxford, Dept Publ Hlth, Oxford, England.
[Calle, E. E.; Gapstur, S. M.; Patel, A. V.] Amer Canc Soc, Atlanta, GA 30329 USA.
[Dal Maso, L.; Talamini, R.] Aviano Canc Ctr, Pordenone, Italy.
[Chetrit, A.; Hirsh-Yechezkel, G.; Lubin, F.; Sadetzki, S.; Natl Israeli Study Ovarian Canc] Gertner Inst, Canc & Radiat Epidemiol Unit, Tel Hashomer, Israel.
[Beral, V.; Gaitskell, K.; Hermon, C.; Moser, K.; Reeves, G.; Banks, E.; Bull, D.; Callaghan, K.; Crossley, B.; Goodill, A.; Green, J.; Key, T.] Canc Epidemiol Unit, Oxford, England.
[Sitas, F.] NSW Canc Council, Canc Res Div, Kings Cross, NSW, Australia.
[Peto, R.; Collins, R.; Doll, R.] Canc Res UK MRC BHF Clin Trial Serv Unit, Oxford, England.
[Peto, R.; Collins, R.; Doll, R.] Epidemiol Studies Unit, Oxford, England.
[Gonzalez, A.] Catalan Inst Oncol, Barcelona, Spain.
[Marchbanks, P.; Lee, N.; Ory, H. W.; Peterson, H. B.; Wingo, P. A.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Martin, N.; Pardthaisong, T.; Silpisornkosol, S.; Theetranont, C.] Chiang Mai Univ, Chiang Mai 50000, Thailand.
[Boosiri, B.; Chutivongse, S.; Jimakorn, P.; Virutamasen, P.; Wongsrichanalai, C.] Chulalongkorn Univ, Bangkok, Thailand.
[Tjonneland, A.] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark.
[Titus-Ernstoff, L.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA.
[Byers, T.] Colorado Sch Publ Hlth, Dept Epidemiol, Denver, CO USA.
[Rohan, T.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Mosgaard, B. J.] Herlev Univ Hosp, Dept Obstet & Gynaecol, Copenhagen, Denmark.
[Vessey, M.; Yeates, D.] Dept Publ Hlth, Oxford, England.
[Freudenheim, J. L.] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
[Chang-Claude, J.; Kaaks, R.] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Anderson, K. E.; Folsom, A.; Robien, K.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA.
[Hampton, J.; Newcomb, P. A.; Rossing, M. A.; Thomas, D. B.; Weiss, N. S.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA.
[Riboli, E.] Univ London Imperial Coll Sci Technol & Med, London, England.
[Clavel-Chapelon, F.] INSERM, U1018, Villejuif, France.
[Clavel-Chapelon, F.] Paris S Univ, Inst Cancerol Gustave Roussy, UMRS 1018, Villejuif, France.
[Cramer, D.; Hankinson, S. E.; Tworoger, S. S.; Nurses Hlth Study] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Hankinson, S. E.; Tworoger, S. S.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
[Franceschi, S.] Int Agcy Res Canc, F-69372 Lyon, France.
[Negri, E.; La Vecchia, C.] Univ Milan, Ist Ric Farmacol Mario Negri, Milan, Italy.
[Adami, H. O.; Magnusson, C.; Riman, T.; Weiderpass, E.; Wolk, A.] Karolinska Inst, Stockholm, Sweden.
[Schouten, L. J.; van den Brandt, P. A.] Maastricht Univ, Maastricht, Netherlands.
[Chantarakul, N.; Koetsawang, S.; Rachawat, D.] Mahidol Univ, Bangkok 10700, Thailand.
[Palli, D.] Canc Res & Prevent Inst, Mol & Nutr Epidemiol Unit, Florence, Italy.
[Black, A.; Brinton, L. A.; Freedman, D. M.; Hartge, P.; Hsing, A. W.; Lacey, J. V., Jr.; Hoover, R. N.; Schairer, C.] NCI, Bethesda, MD 20892 USA.
[Urban, M.] Natl Hlth Lab Serv, NHLS MRC Canc Epidemiol Res Grp, Johannesburg, South Africa.
[Graff-Iversen, S.; Selmer, R.] Norwegian Inst Publ Hlth, Oslo, Norway.
[Bain, C. J.; Green, A. C.; Purdie, D. M.; Siskind, V.; Webb, P. M.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Bain, C. J.; Green, A. C.; Purdie, D. M.; Siskind, V.; Webb, P. M.] Univ Queensland, Brisbane, Qld, Australia.
[Moysich, K.; McCann, S. E.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Hannaford, P.; Kay, C.] Royal Coll Gen Practitioners Oral Contracept Stud, London, England.
[Binns, C. W.; Lee, A. H.; Zhang, M.] Curtin Univ Technol, Sch Publ Hlth, Perth, WA, Australia.
[Ness, R. B.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA.
[Nasca, P.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Boston, MA 02125 USA.
[Coogan, P. F.; Palmer, J. R.; Rosenberg, L.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA.
[Kelsey, J.; Paffenbarger, R.; Whittemore, A.] Stanford Univ, Stanford, CA 94305 USA.
[Katsouyanni, K.; Trichopoulou, A.; Trichopoulos, D.; Tzonou, A.] Univ Athens, Sch Med, GR-11527 Athens, Greece.
[Dabancens, A.; Martinez, L.; Molina, R.; Salas, O.] Univ Chile, Santiago, Chile.
[Goodman, M. T.; Lurie, G.; Carney, M. E.; Wilkens, L. R.] Univ Hawaii, Honolulu, HI 96822 USA.
[Hartman, L.; Manjer, J.; Olsson, H.] Univ Lund Hosp, S-22185 Lund, Sweden.
[Grisso, J. A.; Morgan, M.; Wheeler, J. E.] Univ Penn, Philadelphia, PA 19104 USA.
[Bunker, C. H.; Edwards, R. P.; Modugno, F.] Univ Pittsburgh, Pittsburgh, PA USA.
[Peeters, P. H. M.] Univ Med Ctr Utrecht, Utrecht, Netherlands.
[Casagrande, J.; Pike, M. C.; Ross, R. K.; Wu, A. H.] Univ So Calif, Los Angeles, CA USA.
[Miller, A. B.] Univ Toronto, Toronto, ON, Canada.
[Kumle, M.; Gram, I. T.; Lund, E.] Univ Tromso, Tromso, Norway.
[McGowan, L.] George Washington Univ, Washington, DC USA.
[Shu, X. O.; Zheng, W.] Vanderbilt Univ, Nashville, TN USA.
[Farley, T. M. M.; Holck, S.; Meirik, O.] World Hlth Org, UNDP UNFPA WHO World Bank Special Programme Res D, Geneva, Switzerland.
[Risch, H. A.] Yale Univ, Sch Publ Hlth, Yale, CT USA.
RP Beral, V (reprint author), Univ Oxford, Collaborat Grp Epidemiol Studies Ovarian Canc, Canc Epidemiol Unit, Richard Doll Bldg, Oxford OX3 7LF, England.
EM collaborations@ceu.ox.ac.uk
RI Schouten, Leo/G-3713-2012; Beral, Valerie/B-2979-2013; Binns,
Colin/A-6012-2008; Negri, Eva/B-7244-2013; Webb, Penelope/D-5736-2013;
Clavel-Chapelon, Francoise/G-6733-2014; Brinton, Louise/G-7486-2015;
Weiderpass, Elisabete/M-4029-2016; Gonzalez, Carlos A/O-4651-2014;
OI Sitas, Freddy/0000-0001-9679-1481; La Vecchia,
Carlo/0000-0003-1441-897X; PALLI, Domenico/0000-0002-5558-2437; Robien,
Kim/0000-0002-2120-2280; dal maso, luigino/0000-0001-6163-200X; Negri,
Eva/0000-0001-9712-8526; Webb, Penelope/0000-0003-0733-5930; Brinton,
Louise/0000-0003-3853-8562; Weiderpass, Elisabete/0000-0003-2237-0128;
Gonzalez, Carlos A/0000-0003-2822-9715; Tworoger,
Shelley/0000-0002-6986-7046; Magnusson, Cecilia/0000-0002-8567-6725
FU Cancer Research UK; MRC
FX Cancer Research UK and MRC.
NR 63
TC 37
Z9 37
U1 0
U2 19
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
EI 1474-5488
J9 LANCET ONCOL
JI Lancet Oncol.
PD SEP
PY 2012
VL 13
IS 9
BP 946
EP 956
DI 10.1016/S1470-2045(12)70322-4
PG 11
WC Oncology
SC Oncology
GA 000XZ
UT WOS:000308425600022
ER
PT J
AU Le Pelley, ME
Haselgrove, M
Esber, GR
AF Le Pelley, M. E.
Haselgrove, Mark
Esber, Guillem R.
TI Modeling attention in associative learning: Two processes or one?
SO LEARNING & BEHAVIOR
LA English
DT Article
DE Associative learning; Attention; Classical conditioning; Acquisition;
Stimulus preexposure
ID IRRELEVANT STIMULI; ORIENTING RESPONSE; HYBRID MODEL; ASSOCIABILITY;
BLOCKING; CS; PREDICTIVENESS; REINFORCEMENT; PIGEONS; RATS
AB Certain studies of associative learning show that attention is more substantial to cues that have a history of being predictive of an outcome than to cues that are irrelevant. At the same time, other studies show that attention is more substantial to cues whose outcomes are uncertain than to cues whose outcomes are predictable. This has led to the suggestion of there being two kinds of attention in associative learning: one based upon a mechanism that allocates attention to a cue on the basis of its predictiveness, the other based upon a mechanism that allocates attention to a cue on the basis of its prediction error (e.g., Le Pelley, Quarterly Journal of Experimental Psychology, 57B, 193-243, 2004). As an alternative, it has been demonstrated that the effects of both predictiveness and uncertainty can be accounted for with only one kind of attention: one that emphasizes the role of prediction (Esber & Haselgrove, Proceedings of the Royal Society B, 278, 2553-2561, 2011). Here, we consider the alternative: whether the effects of predictiveness and uncertainty can be reconciled with a model of learning that emphasizes the role of prediction error (Pearce, Kaye, & Hall, 1982). Simulations of this model reveal that, in many cases, it too is able to account for the influence of predictiveness and uncertainty in associative learning.
C1 [Le Pelley, M. E.] Univ New S Wales, Sch Psychol, Sydney, NSW 2052, Australia.
[Haselgrove, Mark] Univ Nottingham, Nottingham NG7 2RD, England.
[Esber, Guillem R.] Natl Inst Drug Abuse, Bethesda, MD USA.
RP Le Pelley, ME (reprint author), Univ New S Wales, Sch Psychol, Sydney, NSW 2052, Australia.
EM m.lepelley@unsw.edu.au
OI Haselgrove, Mark/0000-0001-8981-1181
FU Biotechnology and Biological Sciences Research Council [BB/F01239X/1]
NR 36
TC 5
Z9 5
U1 3
U2 25
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1543-4494
J9 LEARN BEHAV
JI Learn Behav.
PD SEP
PY 2012
VL 40
IS 3
BP 292
EP 304
DI 10.3758/s13420-012-0084-4
PG 13
WC Psychology, Biological; Behavioral Sciences; Psychology, Experimental;
Zoology
SC Psychology; Behavioral Sciences; Zoology
GA 996PA
UT WOS:000308102300005
PM 22927002
ER
PT J
AU Hansen, MS
Sorensen, TS
Arai, AE
Kellman, P
AF Hansen, Michael S.
Sorensen, Thomas S.
Arai, Andrew E.
Kellman, Peter
TI Retrospective reconstruction of high temporal resolution cine images
from real-time MRI using iterative motion correction
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE real-time MRI; parallel MRI; nonrigid motion connection; myocardial
function; non-Cartesian MRI
ID COMMODITY GRAPHICS HARDWARE; LEFT-VENTRICULAR FUNCTION; K-T SENSE; RAPID
EVALUATION; OPTICAL-FLOW; BREATH-HOLD; REGISTRATION; ENHANCEMENT; HEART;
MASS
AB Cardiac function has traditionally been evaluated using breath-hold cine acquisitions. However, there is a great need for free breathing techniques in patients who have difficulty in holding their breath. Real-time cardiac MRI is a valuable alternative to the traditional breath-hold imaging approach, but the real-time images are often inferior in spatial and temporal resolution. This article presents a general method for reconstruction of high spatial and temporal resolution cine images from a real-time acquisition acquired over multiple cardiac cycles. The method combines parallel imaging and motion correction based on nonrigid registration and can be applied to arbitrary k-space trajectories. The method is demonstrated with real-time Cartesian imaging and Golden Angle radial acquisitions, and the motion-corrected acquisitions are compared with raw real-time images and breath-hold cine acquisitions in 10 (N = 10) subjects. Acceptable image quality was obtained in all motion-corrected reconstructions, and the resulting mean image quality score was (a) Cartesian real-time: 2.48, (b) Golden Angle real-time: 1.90 (1.002.50), (c) Cartesian motion correction: 3.92, (d) Radial motion correction: 4.58, and (e) Breath-hold cine: 5.00. The proposed method provides a flexible way to obtain high-quality, high-resolution cine images in patients with difficulty holding their breath. Magn Reson Med, 2012. (c) 2011 Wiley Periodicals, Inc.
C1 [Hansen, Michael S.; Arai, Andrew E.; Kellman, Peter] NHLBI, NIH, Bethesda, MD 20814 USA.
[Sorensen, Thomas S.] Aarhus Univ, Dept Comp Sci, DK-8000 Aarhus, Denmark.
[Sorensen, Thomas S.] Aarhus Univ, Inst Clin Med, DK-8000 Aarhus, Denmark.
RP Hansen, MS (reprint author), NHLBI, NIH, Bldg 10,B1D405,9000 Rockville Pike, Bethesda, MD 20814 USA.
EM michael.hansen@nih.gov
RI Hansen, Michael/J-5391-2015;
OI Hansen, Michael/0000-0002-8087-8731; Sorensen, Thomas
Sangild/0000-0002-8482-7667
FU Division of Intramural Research, National Heart Lung and Blood
Institute, National Institutes of Health, USA
FX Grant sponsors: Division of Intramural Research, National Heart Lung and
Blood Institute, National Institutes of Health, USA.
NR 23
TC 37
Z9 37
U1 6
U2 14
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 2012
VL 68
IS 3
BP 741
EP 750
DI 10.1002/mrm.23284
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 996NY
UT WOS:000308098100010
PM 22190255
ER
PT J
AU Abd-Elmoniem, KZ
Barmet, C
Stuber, M
AF Abd-Elmoniem, Khaled Z.
Barmet, Christoph
Stuber, Matthias
TI Free-breathing inner-volume black-blood imaging of the human heart using
two-dimensionally selective local excitation at 3 T
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE 2D-selective RF pulses; black-blood; local excitation
ID CORONARY MR-ANGIOGRAPHY; TURBO SPIN-ECHO; REDUCED B-1 INHOMOGENEITY;
RADIO-FREQUENCY PULSES; CAROTID-ARTERY WALL; NAVIGATOR CORRECTION;
INVERSION; DESIGN; SUPPRESSION; 1.5T
AB Black-blood fast spin-echo imaging is a powerful technique for the evaluation of cardiac anatomy. To avoid fold-over artifacts, using a sufficiently large field of view in phase-encoding direction is mandatory. The related oversampling affects scanning time and respiratory chest motion artifacts are commonly observed. The excitation of a volume that exclusively includes the heart without its surrounding structures may help to improve scan efficiency and minimize motion artifacts. Therefore, and by building on previously reported inner-volume approach, the combination of a black-blood fast spin-echo sequence with a two-dimensionally selective radiofrequency pulse is proposed for selective local excitation small field of view imaging of the heart. This local excitation technique has been developed, implemented, and tested in phantoms and in vivo. With this method, small field of view imaging of a user-specified region in the human thorax is feasible, scanning becomes more time efficient, motion artifacts can be minimized, and additional flexibility in the choice of imaging parameters can be exploited. Magn Reson Med, 2012. (c) 2011 Wiley Periodicals, Inc.
C1 [Abd-Elmoniem, Khaled Z.] NIDDK, Biomed & Metab Imaging Branch, NIH, Bethesda, MD 20892 USA.
[Barmet, Christoph] Swiss Fed Inst Technol, Zurich, Switzerland.
[Stuber, Matthias] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA.
[Stuber, Matthias] Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA.
[Stuber, Matthias] Univ Lausanne Hosp, Dept Radiol, Lausanne, Switzerland.
[Stuber, Matthias] Ctr Biomed Imaging CIBM, Lausanne, Switzerland.
RP Abd-Elmoniem, KZ (reprint author), NIDDK, Biomed & Metab Imaging Branch, NIH, Bldg 10,CRC Room 3-5340, Bethesda, MD 20892 USA.
EM abdelmoniemkz@mail.nih.gov
RI Centre d'imagerie Biomedicale, CIBM/B-5740-2012; Abd-Elmoniem,
Khaled/B-9289-2008;
OI Abd-Elmoniem, Khaled/0000-0002-1001-1702; Stuber,
Matthias/0000-0001-9843-2028
FU NIH/NHLBI [RO1HL084186]
FX Grant sponsor: NIH/NHLBI; Grant number: RO1HL084186.
NR 36
TC 4
Z9 4
U1 0
U2 5
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 2012
VL 68
IS 3
BP 822
EP 829
DI 10.1002/mrm.23305
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 996NY
UT WOS:000308098100018
PM 22161817
ER
PT J
AU Qian, CQ
Murphy-Boesch, J
Dodd, S
Koretsky, A
AF Qian, Chunqi
Murphy-Boesch, Joseph
Dodd, Stephen
Koretsky, Alan
TI Sensitivity enhancement of remotely coupled NMR detectors using
wirelessly powered parametric amplification
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE parametric amplifier; varactor; wireless
ID MAGNETIC-RESONANCE; HIGH-RESOLUTION; INVIVO NMR; MRI; COIL; GUIDES
AB A completely wireless detection coil with an integrated parametric amplifier has been constructed to provide local amplification and transmission of MR signals. The sample coil is one element of a parametric amplifier using a zero-bias diode that mixes the weak MR signal with a strong pump signal that is obtained from an inductively coupled external loop. The NMR sample coil develops current gain via reduction in the effective coil resistance. Higher gain can be obtained by adjusting the level of the pumping power closer to the oscillation threshold, but the gain is ultimately constrained by the bandwidth requirement of MRI experiments. A feasibility study here shows that on a NaCl/D2O phantom, 23Na signals with 20 dB of gain can be readily obtained with a concomitant bandwidth of 144 kHz. This gain is high enough that the integrated coil with parametric amplifier, which is coupled inductively to external loops, can provide sensitivity approaching that of direct wire connection. Magn Reson Med, 2012. (c) 2012 Wiley Periodicals, Inc.
C1 [Qian, Chunqi; Murphy-Boesch, Joseph; Dodd, Stephen; Koretsky, Alan] NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
RP Qian, CQ (reprint author), NINDS, Lab Funct & Mol Imaging, NIH, 10 Ctr Dr,Room 3D17, Bethesda, MD 20892 USA.
EM qianc2@ninds.nih.gov
RI Qian, Chunqi/A-7481-2012; Koretsky, Alan/C-7940-2015
OI Koretsky, Alan/0000-0002-8085-4756
FU NIH, NINDS
FX Grant sponsors: NIH, NINDS (Intramural Research Program)
NR 19
TC 10
Z9 10
U1 0
U2 9
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 2012
VL 68
IS 3
BP 989
EP 996
DI 10.1002/mrm.23274
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 996NY
UT WOS:000308098100038
PM 22246567
ER
PT J
AU Malhotra, M
Monga, V
Sharma, S
Jain, J
Samad, A
Stables, J
Deep, A
AF Malhotra, Manav
Monga, Vikramdeep
Sharma, Sagun
Jain, Jainendra
Samad, Abdul
Stables, James
Deep, Aakash
TI Synthesis, characterization and pharmacological evaluation of (E)-N
'-(substituted-benzylidene)isonicotinohydrazide derivatives as potent
anticonvulsant agents
SO MEDICINAL CHEMISTRY RESEARCH
LA English
DT Article
DE Isoniazid; (E)-N '-(substituted-benzylidene)isonicotinohydrazide;
Anticonvulsant; Pentylenetetrazole; Neurotoxicity
ID ANTIEPILEPTIC DRUG DEVELOPMENT; SEMICARBAZONES; ARYL
AB A series of (E)-N'-(substituted-benzylidene)isonicotinohydrazide derivatives were synthesized by coupling it with different substituted aldehydes, acetophenone, and benzophenones in presence of absolute ethanol along with catalytic amount of glacial acetic acid. All the synthesized compound were confirmed and characterized by using various spectral technique like IR, H-1 NMR, C-13 NMR, and mass spectroscopy studies. Anticonvulsant evaluations of all the synthesized compounds were done using various seizures models like maximal electroshock-induced seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) at a dose of 30, 100, and 300 mg/kg body weight and anticonvulsant activity was noted at 0.5 h and 4 h time intervals after the drug administration. Compound 1a (E)-N'-2-benzylidene isonicotinohydrazide, 1g (E)-N'-2-ethoxybenzylidene isonicotinohydrazide, 1k (E)-N'-3-flourobenzylidene isonicotinohydrazide and 3a (E)-N'-diphenylmethylene isonicotinohydrazide showed protection in MES model, which indicates that these compounds have the ability to prevent the spread of seizure at 300 mg/kg dose and showed protection at 0.5 h duration. Compound 3a was also found to be active in scPTZ screen at a dose of 300 mg/kg. In neurotoxicity screen, all the synthesized compounds were found non-toxic except compounds 1n, 2a, and 3b. Further compounds 1a, 1g, 1k, and 3a were also evaluated in the minimal clonic seizure model and exhibited potent anticonvulsant activity with lower neurotoxicity. Among all synthesized derivatives, analogue 3a was found to exhibit protection in MES and scPTZ seizure models. This study proved that isonicotinoyl hydrazides synthesized by condensing isoniazid with various aldehydes and ketones displayed moderate to potent anticonvulsant activity.
C1 [Deep, Aakash] Maharshi Dayanand Univ, Dept Pharmaceut Sci, Rohtak 124001, Haryana, India.
[Malhotra, Manav; Monga, Vikramdeep; Sharma, Sagun] ISF Coll Pharm, Dept Pharmaceut Chem, Moga 142001, India.
[Monga, Vikramdeep] Adesh Inst Med Sci & Res, Adesh Inst Pharm & Biomed Sci, Bathinda 151001, India.
[Jain, Jainendra] Ram Eash Inst Tech & Vocat Studies, Dept Pharmaceut Chem, Greater Noida 201310, India.
[Samad, Abdul] King Saud Univ, Coll Pharm Al Kharj, Dept Pharmaceut Chem, Riyadh, Saudi Arabia.
[Stables, James] NINDS, NIH, Bethesda, MD 20892 USA.
RP Deep, A (reprint author), Maharshi Dayanand Univ, Dept Pharmaceut Sci, Rohtak 124001, Haryana, India.
EM aakashdeep82@gmail.com
OI Deep, Aakash /0000-0002-8800-8722
NR 29
TC 4
Z9 4
U1 0
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1054-2523
J9 MED CHEM RES
JI Med. Chem. Res.
PD SEP
PY 2012
VL 21
IS 9
BP 2145
EP 2152
DI 10.1007/s00044-011-9739-5
PG 8
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 985LO
UT WOS:000307268100003
ER
PT J
AU Kumar, P
Shrivastava, B
Pandeya, SN
Tripathi, L
Stables, JP
AF Kumar, Praveen
Shrivastava, Birendra
Pandeya, Surendra N.
Tripathi, Laxmi
Stables, James P.
TI Design, synthesis, and anticonvulsant evaluation of some novel 1, 3
benzothiazol-2-yl hydrazones/acetohydrazones
SO MEDICINAL CHEMISTRY RESEARCH
LA English
DT Article
DE 2-[2-(substituted)hydrazinyl]-1,3-benzothiazole;
2-(1,3-benzothiazol-2-ylsulfanyl)-N '-(substituted)acetohydrazide; 6 Hz
psychomotor seizure test; Neurotoxicity; Computational study
ID ANTIEPILEPTIC DRUGS; SEMICARBAZONES; INHIBITORS; DISCOVERY
AB A series of 2-[2-(substituted)hydrazinyl]-1,3-benzothiazole and 2-(1,3-benzothiazol-2-ylsulfanyl)-N'-(substituted)acetohydrazide were designed and synthesized keeping in view the structural requirement of pharmacophore and evaluated for anticonvulsant activity and neurotoxicity. The anticonvulsant activity of the titled compounds was assessed using the 6 Hz psychomotor seizure test. The most active compound of the series was 2-(1,3-benzothiazol-2-ylsulfanyl)-N'-[4-(4-bromophenoxy)benzylidene]acetohydrazide BT 15, which showed 75% protection (3/4, 1.0 h) and 50% protection (2/4, 0.5 h) at a dose of 100 mg/kg in mice. A computational study was carried out for calculation of pharmacophore pattern and prediction of pharmacokinetic properties. Titled compounds have also exhibited good binding properties with epilepsy molecular targets such as GABA (A) alpha-1, glutamate, GABA (A) delta receptors and Na/H exchanger, in Lamarckian genetic algorithm-based flexible docking studies.
C1 [Kumar, Praveen; Shrivastava, Birendra] Jaipur Natl Univ, Sch Pharmaceut Sci, Jaipur 302025, Rajasthan, India.
[Pandeya, Surendra N.] Saroj Inst Technol & Management, Lucknow 226002, Uttar Pradesh, India.
[Tripathi, Laxmi] SD Coll Pharm & Vocat Studies, Muzaffarnagar 251001, Uttar Pradesh, India.
[Stables, James P.] NIH, Preclin Pharmacol Sect, Epilepsy Branch, Bethesda, MD 20892 USA.
RP Kumar, P (reprint author), Jaipur Natl Univ, Sch Pharmaceut Sci, Jaipur 302025, Rajasthan, India.
EM praveensha1977@rediffmail.com
NR 19
TC 12
Z9 13
U1 0
U2 8
PU SPRINGER BIRKHAUSER
PI NEW YORK
PA 233 SPRING STREET, 6TH FLOOR, NEW YORK, NY 10013 USA
SN 1054-2523
J9 MED CHEM RES
JI Med. Chem. Res.
PD SEP
PY 2012
VL 21
IS 9
BP 2428
EP 2442
DI 10.1007/s00044-011-9768-0
PG 15
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 985LO
UT WOS:000307268100034
ER
PT J
AU Majumdar, A
Curley, SA
Wu, XF
Brown, P
Hwang, JP
Shetty, K
Yao, ZX
He, AR
Li, SL
Katz, L
Farci, P
Mishra, L
AF Majumdar, Avijit
Curley, Steven A.
Wu, Xifeng
Brown, Powel
Hwang, Jessica P.
Shetty, Kirti
Yao, Zhi-Xing
He, Aiwu Ruth
Li, Shulin
Katz, Lior
Farci, Patrizia
Mishra, Lopa
TI Hepatic stem cells and transforming growth factor beta in hepatocellular
carcinoma
SO NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
LA English
DT Review
ID UBIQUITIN LIGASE COMPLEX; TGF-BETA; VITAMIN-D; LIVER-CANCER; DNA-DAMAGE;
THERAPEUTIC TARGETS; COLORECTAL-CANCER; MOLECULAR-BASIS;
DOWN-REGULATION; SELF-RENEWAL
AB Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers worldwide. It arises from modulation of multiple genes by mutations, epigenetic regulation, noncoding RNAs and translational modifications of encoded proteins. Although >40% of HCCs are clonal and thought to arise from cancer stem cells (CSCs), the precise identification and mechanisms of CSC formation remain poorly understood. A functional role of transforming growth factor (TGF)-beta signalling in liver and intestinal stem cell niches has been demonstrated through mouse genetics. These studies demonstrate that loss of TGF-beta signalling yields a phenotype similar to a human CSC disorder, Beckwith-Wiedemann syndrome. Insights into this powerful pathway will be vital for developing new therapeutics in cancer. Current clinical approaches are aimed at establishing novel cancer drugs that target activated pathways when the TGF-beta tumour suppressor pathway is lost, and TGF-beta itself could potentially be targeted in metastases. Studies delineating key functional pathways in HCC and CSC formation could be important in preventing this disease and could lead to simple treatment strategies; for example, use of vitamin D might be effective when the TGF-beta pathway is lost or when wnt signalling is activated.
C1 [Majumdar, Avijit; Yao, Zhi-Xing; Katz, Lior; Mishra, Lopa] Univ Texas MD Anderson Canc Ctr, Dept Gastroenterol Hepatol & Nutr, Houston, TX 77030 USA.
[Curley, Steven A.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA.
[Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Brown, Powel] Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77030 USA.
[Hwang, Jessica P.] Univ Texas MD Anderson Canc Ctr, Dept Gen Internal Med, Houston, TX 77030 USA.
[Li, Shulin] Univ Texas MD Anderson Canc Ctr, Dept Pediat Res, Houston, TX 77030 USA.
[Shetty, Kirti] Georgetown Univ Hosp, Georgetown Transplant Inst, Washington, DC 20007 USA.
[He, Aiwu Ruth] Georgetown Univ Hosp, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.
[Farci, Patrizia] NIAID, Pathogenesis Sect, NIH, DHHS, Bethesda, MD 20892 USA.
RP Mishra, L (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gastroenterol Hepatol & Nutr, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM lmishra@mdanderson.org
FU National Institutes of Health [RO1-CA106614, RO1-CA042857, PO1-CA130821,
RC2-AA019392]; Ben Orr Award; National Institute of Allergy and
Infectious Diseases; [P30-CA016672]; [P30-DK56338]
FX We thank Beth Allen and Wilma Jogunoori for critical review of the
manuscript. L. Mishra's work was supported by National Institutes of
Health RO1-CA106614, RO1-CA042857, PO1-CA130821, RC2-AA019392, R. Robert
and Sally D. Funderburg Research Scholar, the Ben Orr Award, and
P30-CA016672, P30-DK56338 and P. Farci's work is supported by the
Intramural Research Program of the National Institutes of Health and
National Institute of Allergy and Infectious Diseases.
NR 128
TC 46
Z9 51
U1 0
U2 29
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-5045
J9 NAT REV GASTRO HEPAT
JI Nat. Rev. Gastroenterol. Hepatol.
PD SEP
PY 2012
VL 9
IS 9
BP 530
EP 538
DI 10.1038/nrgastro.2012.114
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 002BB
UT WOS:000308503900007
PM 22710573
ER
PT J
AU Hasler, W
May, P
Pasricha, P
Parkman, H
Abell, T
Koch, K
Mccallum, R
Sarosiek, I
Nguyen, L
Snape, W
Calles, J
Farrugia, G
Tonascia, J
Lee, L
Unalp-Arida, A
Hamilton, F
AF Hasler, W.
May, P.
Pasricha, P.
Parkman, H.
Abell, T.
Koch, K.
Mccallum, R.
Sarosiek, I.
Nguyen, L.
Snape, W.
Calles, J.
Farrugia, G.
Tonascia, J.
Lee, L.
Unalp-Arida, A.
Hamilton, F.
TI Correlates of temporal variability of symptoms in gastroparesis
SO NEUROGASTROENTEROLOGY AND MOTILITY
LA English
DT Meeting Abstract
C1 [Hasler, W.] Univ Michigan, Dept Gastroenterol, Ann Arbor, MI 48109 USA.
[May, P.] Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA.
[Pasricha, P.; Nguyen, L.] Stanford Univ, Dept Gastroenterol, Palo Alto, CA 94304 USA.
[Parkman, H.] Temple Univ, Dept Gastroenterol, Philadelphia, PA 19122 USA.
[Abell, T.] Univ Mississippi, Dept Gastroenterol, Jackson, MS 39216 USA.
[Koch, K.] Wake Forest Univ, Dept Gastroenterol, Winston Salem, NC 27109 USA.
[Mccallum, R.; Sarosiek, I.] Texas Tech Univ, Dept Gastroenterol, El Paso, TX USA.
[Snape, W.] Calif Pacific Med Ctr, Dept Gastroenterol, San Francisco, CA USA.
[Calles, J.] Wake Forest Univ, Dept Endocrinol, Winston Salem, NC 27109 USA.
[Farrugia, G.] Mayo Clin, Rochester, MN USA.
[Tonascia, J.; Unalp-Arida, A.] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA.
[Lee, L.] Johns Hopkins Univ, Dept Gastroenterol, Baltimore, MD USA.
[Hamilton, F.] NIDDKD, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1350-1925
J9 NEUROGASTROENT MOTIL
JI Neurogastroenterol. Motil.
PD SEP
PY 2012
VL 24
SU 2
BP 18
EP 19
PG 2
WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences
SC Gastroenterology & Hepatology; Neurosciences & Neurology
GA 001BS
UT WOS:000308435400063
ER
PT J
AU Parkman, H
Wilson, L
Pasricha, P
Koch, K
Snape, W
Abell, T
Hasler, W
Lee, L
Nguyen, L
Mccallum, R
Sarosiek, I
Farrugia, G
Unalp-Arida, A
Tonascia, J
Hamilton, F
AF Parkman, H.
Wilson, L.
Pasricha, P.
Koch, K.
Snape, W.
Abell, T.
Hasler, W.
Lee, L.
Nguyen, L.
Mccallum, R.
Sarosiek, I.
Farrugia, G.
Unalp-Arida, A.
Tonascia, J.
Hamilton, F.
TI Reconfiguring the Gastroparesis Cardinal Symptom Index (GCSI)
SO NEUROGASTROENTEROLOGY AND MOTILITY
LA English
DT Meeting Abstract
C1 [Parkman, H.] Temple Univ, Dept Med, Dept Gastroenterol, Philadelphia, PA 19122 USA.
[Wilson, L.; Unalp-Arida, A.; Tonascia, J.] Johns Hopkins Univ, Baltimore, MD USA.
[Pasricha, P.] Stanford Univ, San Francisco, CA USA.
[Koch, K.] Wake Forest, Wake Forest, NC USA.
[Snape, W.] Calif Pacific Med, San Francisco, CA USA.
[Sarosiek, I.] Texas Tech Univ, El Paso, TX USA.
[Farrugia, G.] Mayo Clin, Rochester, MN USA.
[Hamilton, F.] NIH, Bethesda, MD 20892 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 1350-1925
J9 NEUROGASTROENT MOTIL
JI Neurogastroenterol. Motil.
PD SEP
PY 2012
VL 24
SU 2
BP 19
EP 19
PG 1
WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences
SC Gastroenterology & Hepatology; Neurosciences & Neurology
GA 001BS
UT WOS:000308435400064
ER
PT J
AU Madkour, AS
Farhat, T
Halpern, CT
Gabhainn, SN
Godeau, E
AF Madkour, Aubrey Spriggs
Farhat, Tilda
Halpern, Carolyn Tucker
Gabhainn, Saoirse Nic
Godeau, Emmanuelle
TI Parents' Support and Knowledge of Their Daughters' Lives, and Females'
Early Sexual Initiation In Nine European Countries
SO PERSPECTIVES ON SEXUAL AND REPRODUCTIVE HEALTH
LA English
DT Article
ID BONDING INSTRUMENT; FAMILY-STRUCTURE; HEALTH BEHAVIOR; 5 NATIONS;
ADOLESCENTS; REINTERPRETATION; SYMPTOMS; SAMPLE; DEBUT; YOUTH
AB CONTEXT: Associations between early sexual initiation and parental support and knowledge have not been uniformly tested in multiple European population-based samples. Understanding such associations is important in efforts to discourage females' early sex.
METHODS: Data were compiled for 7,466 females aged 14-16 who participated in the 2005-2006 Health Behaviors in School-Aged Children survey in nine countries (Austria, Finland, Greece, Hungary, Iceland, Lithuania, Romania, Spain and Ukraine). Univariate, bivariate and multivariable analyses were run with standard error corrections and weights to assess how sexual initiation before age 16 was related to maternal and paternal support and knowledge of daily activities.
RESULTS: Prevalence of early sexual initiation ranged from 7% (in Romania) to 35% (in Iceland). In bivariate analyses, maternal and paternal support were significantly negatively related to adolescent females' early sexual initiation in most countries. In models with demographic controls, parental support was negatively associated with early sexual initiation (odds ratio, 0.8 for maternal and 0.7 for paternal). After parental knowledge was added, early sexual initiation was no longer associated with parental support, but was negatively associated with maternal and paternal knowledge (0.7 for each). These patterns held across countries.
CONCLUSIONS: Parental knowledge largely explained negative associations between parental support and early initiation, suggesting either that knowledge is more important than support or that knowledge mediates the association between support and early sex. Perspectives on Sexual and Reproductive Health, 2012, 44(3):167-175, doi: 10.1363/4416712
C1 [Madkour, Aubrey Spriggs] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Global Community Hlth & Behav Sci, New Orleans, LA 70118 USA.
[Farhat, Tilda] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA.
[Halpern, Carolyn Tucker] Univ N Carolina, Dept Maternal & Child Hlth, Chapel Hill, NC USA.
[Halpern, Carolyn Tucker] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA.
[Gabhainn, Saoirse Nic] Natl Univ Ireland Galway, Hlth Promot Ctr, Sch Hlth Sci, Galway, Ireland.
[Godeau, Emmanuelle] Univ Toulouse 3, INSERM, U1027, F-31062 Toulouse, France.
RP Madkour, AS (reprint author), Tulane Univ, Sch Publ Hlth & Trop Med, Dept Global Community Hlth & Behav Sci, New Orleans, LA 70118 USA.
EM aspriggs@tulane.edu
FU NICHD NIH HHS [N01-HD-5-3401, L40 HD066680, R24 HD050924]; PHS HHS
[T76MC04927]
NR 50
TC 7
Z9 7
U1 1
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1538-6341
J9 PERSPECT SEX REPRO H
JI Perspect. Sex Reprod. Health
PD SEP
PY 2012
VL 44
IS 3
BP 167
EP 175
DI 10.1363/4416712
PG 9
WC Demography; Family Studies
SC Demography; Family Studies
GA 002OL
UT WOS:000308541400003
PM 22958661
ER
PT J
AU Cullinane, AR
Curry, JA
Golas, G
Pan, J
Carmona-Rivera, C
Hess, RA
White, JG
Huizing, M
Gahl, WA
AF Cullinane, Andrew R.
Curry, James A.
Golas, Gretchen
Pan, James
Carmona-Rivera, Carmelo
Hess, Richard A.
White, James G.
Huizing, Marjan
Gahl, William A.
TI A BLOC-1 mutation screen reveals a novel BLOC1S3 mutation in
Hermansky-Pudlak Syndrome type 8
SO PIGMENT CELL & MELANOMA RESEARCH
LA English
DT Article
DE Hermansky-Pudlak Syndrome; BLOC-1; HPS-8; BLOC1S3
ID LYSOSOME-RELATED ORGANELLES; PROTEIN COMPLEX; BIOGENESIS; GENE;
TRAFFICKING; MELANOSOMES; PALLIDIN; HPS4
AB HermanskyPudlak Syndrome (HPS) is a genetically heterogeneous disorder of lysosome-related organelle biogenesis and is characterized by oculocutaneous albinism and a bleeding diathesis. Over the past decade, we screened 250 patients with HPS-like symptoms for mutations in the genes responsible for HPS subtypes 16. We identified 38 individuals with no functional mutations, and therefore, we analyzed all eight genes encoding the biogenesis of lysosome-related organelles complex-1 (BLOC-1) proteins in these individuals. Here, we describe the identification of a novel nonsense mutation in BLOC1S3 (HPS-8) in a 6-yr-old Iranian boy. This mutation caused nonsense-mediated decay of BLOC1S3 mRNA and destabilized the BLOC-1 complex. Our patients melanocytes showed aberrant localization of TYRP1, with increased plasma membrane trafficking. These findings confirm a common cellular defect for HPS patients with defects in BLOC-1 subunits. We identified only two patients with BLOC-1 defects in our cohort, suggesting that other HPS genes remain to be identified.
C1 [Cullinane, Andrew R.; Curry, James A.; Pan, James; Carmona-Rivera, Carmelo; Hess, Richard A.; Huizing, Marjan; Gahl, William A.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Golas, Gretchen; Gahl, William A.] NIH, Intramural Off Rare Dis Res, Off Director, Bethesda, MD 20892 USA.
[White, James G.] Univ Minnesota, Dept Lab Med, Minneapolis, MN 55455 USA.
RP Cullinane, AR (reprint author), NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
EM andrew.cullinane@nih.gov
FU National Human Genome Research Institute, National Institutes of Health,
Bethesda, MD, USA
FX We appreciate the excellent technical assistance of Roxanne Fischer and
Carla Ciccone. We thank Dr. Thomas Markello for assistance with SNP
arrays and Dr. E. Dell'Angelica for supplying the pallidin antibody.
This study was supported by the Intramural Research Program of the
National Human Genome Research Institute, National Institutes of Health,
Bethesda, MD, USA. All authors declare no conflicts of interest.
NR 20
TC 8
Z9 8
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-1471
J9 PIGM CELL MELANOMA R
JI Pigment Cell Melanoma Res.
PD SEP
PY 2012
VL 25
IS 5
BP 584
EP 591
DI 10.1111/j.1755-148X.2012.01029.x
PG 8
WC Oncology; Cell Biology; Dermatology
SC Oncology; Cell Biology; Dermatology
GA 996NL
UT WOS:000308096200010
PM 22709368
ER
PT J
AU Wiener, L
Oppenheim, D
Breyer, J
Battles, H
Zadeh, S
Patenaude, AF
AF Wiener, Lori
Oppenheim, Daniel
Breyer, Joanna
Battles, Haven
Zadeh, Sima
Patenaude, Andrea Farkas
TI A worldview of the professional experiences and training needs of
pediatric psycho-oncologists
SO PSYCHO-ONCOLOGY
LA English
DT Article
DE pediatrics; psycho-oncology; childhood cancer; training; professional
rewards; clinical challenges
ID BURNOUT; STRESS
AB Background Thirty years after the origin of the field of psycho-oncology, limited data exist about the work practices of professionals providing psychosocial care to children with cancer and their families. Method A survey was designed to assess training, work environment, theoretical orientation, services provided, subspecialty areas or areas of special interest, satisfactions, challenges, and continuing education needs of pediatric psycho-oncologists. Members of national and international psycho-oncology organizations were invited to participate in the web-based survey. Results Seven hundred eighty-six professionals from 63 countries responded. The sample consisted mostly of psychologists (41%), physicians (20%), and social workers (14%). Approximately half of the participants worked in a designated psycho-oncology unit. Psychologists and social workers provided the majority of psychosocial services. Individual sessions with parents were most common (42%), followed by sessions with children (41%), survivors (36%), families (31%), and siblings (25%). Therapies provided include cognitive behavioral therapy (50%), relaxation (43%), psychodynamic psychotherapy (27%), play therapy (26%), and imagery (23%). Two-thirds reported having appropriate supervision, 37% were conducting research, and only half felt their salary was appropriate. Differences in therapeutic modalities were found by country. Clinicians desire training on clinical interventions, improving communication with medical staff, research, and ethics. Conclusions An international cohort of clinicians providing pediatric psycho-oncology services perform a wide variety of tasks, use a range of therapeutic approaches, and report considerable work satisfaction. Problem areas include professional inter-relations, inadequate supervision, and need for additional specialized training. Opportunity exists for global collaboration in pediatric psycho-oncology research and practices to enhance clinical effectiveness and reduce professional isolation. Copyright (c) 2012 John Wiley & Sons, Ltd.
C1 [Wiener, Lori; Battles, Haven; Zadeh, Sima] NCI, Behav Sci Core, Psychosocial Support & Res Program, Pediat Oncol Branch,Ctr Canc Res, Bethesda, MD 20892 USA.
[Breyer, Joanna; Patenaude, Andrea Farkas] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA.
[Breyer, Joanna; Patenaude, Andrea Farkas] Childrens Hosp, Dept Psychiat, Boston, MA 02115 USA.
[Breyer, Joanna; Patenaude, Andrea Farkas] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Oppenheim, Daniel] Inst Sensorial Dev Children Visual Impairment IDE, Paris, France.
RP Wiener, L (reprint author), NCI, Behav Sci Core, Psychosocial Support & Res Program, Pediat Oncol Branch,Ctr Canc Res, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM wienerl@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX The authors would like to acknowledge the support of several individuals
who helped make this work possible. Elliot Graham (IPOS) and Martha
Grootenhuis (SIOP) were instrumental in the distribution of the survey
information. At NCI, we would like to thank Caroline Crum, Nia Billings,
and Lauren Latella who assisted with the coding of the qualitative data.
We also appreciate the insights provided to us by the Pediatric SIG
Members at both IPOS and APOS. This work is supported in part by the
Intramural Research Programs of the NIH, National Cancer Institute,
Center for Cancer Research.
NR 19
TC 5
Z9 5
U1 2
U2 15
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 2012
VL 21
IS 9
BP 944
EP 953
DI 10.1002/pon.3064
PG 10
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA 999GY
UT WOS:000308299000006
PM 22461180
ER
PT J
AU Dunton, GF
Berrigan, D
Ballard-Barbash, R
Perna, F
Graubard, BI
Atienza, AA
AF Dunton, Genevieve Fridlund
Berrigan, David
Ballard-Barbash, Rachel
Perna, Frank
Graubard, Barry I.
Atienza, Audie A.
TI Differences in the Intensity and Duration of Adolescents' Sports and
Exercise Across Physical and Social Environments
SO RESEARCH QUARTERLY FOR EXERCISE AND SPORT
LA English
DT Article
DE gender; health surveys; leisure time
ID TIME USE SURVEY; INTRINSIC MOTIVATION; ADULTS; YOUTH; PARTICIPATION;
COOPERATION; COMPETITION; BEHAVIOR; GENDER; SCHOOL
AB We used data from the American Time Use Survey (years 2003-06) to analyze whether the intensity and duration of high school students' (ages 15-18 years) sports and exercise bouts differed across physical and social environments. Boys' sports and exercise bouts were more likely to reach a vigorous intensity when taking place at school and with friends/acquaintances/other people; whereas girls' sports and exercise bouts were more likely to reach a vigorous intensity when outdoors and alone. For boys and girls, bout durations were greater at school and with friends/acquaintances/other people than in other environments. Overall, environmental influences on the intensity Gut not duration of sports and exercise bouts appear to differ between boys and girls.
C1 [Dunton, Genevieve Fridlund] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Berrigan, David; Ballard-Barbash, Rachel; Perna, Frank; Atienza, Audie A.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Graubard, Barry I.] NCI, Div Canc Epidemiol & Biostat, Bethesda, MD 20892 USA.
RP Dunton, GF (reprint author), Univ So Calif, Dept Prevent Med, Soto St Bldg SSB,2001 Soto N St,3rd Floor,MC 9239, Los Angeles, CA 90033 USA.
EM dunton@usc.edu
NR 44
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Z9 1
U1 2
U2 12
PU AMER ALLIANCE HEALTH PHYS EDUC REC & DANCE
PI RESTON
PA 1900 ASSOCIATION DRIVE, RESTON, VA 22091 USA
SN 0270-1367
J9 RES Q EXERCISE SPORT
JI Res. Q. Exerc. Sport
PD SEP
PY 2012
VL 83
IS 3
BP 376
EP 382
PG 7
WC Hospitality, Leisure, Sport & Tourism; Psychology, Applied; Psychology;
Sport Sciences
SC Social Sciences - Other Topics; Psychology; Sport Sciences
GA 999AL
UT WOS:000308281400002
PM 22978186
ER
PT J
AU Harvey, PD
Heaton, RK
Carpenter, WT
Green, MF
Gold, JM
Schoenbaum, M
AF Harvey, Philip D.
Heaton, Robert K.
Carpenter, William T., Jr.
Green, Michael F.
Gold, James M.
Schoenbaum, Michael
TI Functional impairment in people with schizophrenia: Focus on
employability and eligibility for disability compensation
SO SCHIZOPHRENIA RESEARCH
LA English
DT Review
DE Disability; Employment
ID SEVERE MENTAL-ILLNESS; PSYCHOTIC AFFECTIVE-DISORDERS; LONG-STAY
PATIENTS; QUALITY-OF-LIFE; OLDER PATIENTS; NEUROPSYCHOLOGICAL FUNCTION;
SCHIZOAFFECTIVE DISORDER; NEUROCOGNITIVE DEFICITS; BASE-LINE;
1ST-EPISODE SCHIZOPHRENIA
AB Background: The Social Security Administration (SSA) is considering whether schizophrenia may warrant inclusion in their new "Compassionate Allowances" process, which aims to identify diseases and other medical conditions that invariably quality for Social Security disability benefits and require no more than minimal objective medical information. This paper summarizes evidence on the empirical association between schizophrenia and vocational disability. A companion paper examines the reliability and validity of schizophrenia diagnosis which is critically relevant for granting a long-term disability on the basis of current diagnosis.
Methods: This is a selective literature review and synthesis, based on a work plan developed in a meeting of experts convened by the National Institute of Mental Health and the SSA. This review of the prevalence of disability is focused on the criteria for receipt of disability compensation for psychotic disorders currently employed by the SSA.
Results: Disability in multiple functional domains is detected in nearly every person with schizophrenia. Clinical remission is much more common than functional recovery, but most patients experience occasional relapses even with treatment adherence, and remissions do not predict functional recovery. Under SSA's current disability determination process, approximately 80% of SSDI/SSI applications in SSA's diagnostic category of "Schizophrenia/Paranoid Functional Disorders" are allowed, compared to around half of SSDI/SSI applications overall. Moreover, the allowance rate is even higher among applicants with schizophrenia. Many unsuccessful applicants are not denied, but rather simply are unable to manage the process of appeal after initial denials.
Discussion: Research evidence suggests that disability applicants with a valid diagnosis of schizophrenia have significant impairment across multiple dimensions of functioning, and will typically remain impaired for the duration of normal working ages or until new interventions are developed. (C) 2012 Elsevier B. V. All rights reserved.
C1 [Harvey, Philip D.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Heaton, Robert K.] UCSD Med Ctr, San Diego, CA USA.
[Carpenter, William T., Jr.; Green, Michael F.] Maryland Psychiat Res Inst, Baltimore, MD USA.
[Green, Michael F.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Schoenbaum, Michael] NIMH, Bethesda, MD 20892 USA.
RP Harvey, PD (reprint author), Univ Miami, Miller Sch Med, 1120 NW 14th St,Suite 1450, Miami, FL 33136 USA.
EM pharvey@med.miami.edu
FU National Institute of Mental Health; Bristol Myers Squibb; Eli Lilly and
Company; Lundbeck Pharma; Merck and Company
FX This research was funded by the National Institute of Mental Health, who
provided no input into the reviews conducted and presentation of these
data. The views expressed in this article do not necessarily represent
the views of the National Institute of Mental Health, the National
Institutes of Health, the Department of Health and Human Services, or
the United States government. This was the result of a committee effort
including other individuals not directly involved as authors, including
Robert Drake, MD, Susan McGurk, PhD, and Howard Goldman, MD.; In the
past 12 months, the authors have the following activities to disclose:
Dr. Harvey has received consulting fees for Abbott Labs, Boeheringer
Engelheim, Genentech, Johnson and Johnson, Pharma Neuroboost, Roche
Pharma, Shire Pharma, Sunovion Pharma, and Takeda Pharma. Dr. Carpenter
has received consulting fees from Bristol Myers Squibb, Eli Lilly and
Company, Lundbeck Pharma, and Merck and Company. Dr. Green has been a
Consultant to Abbott Laboratories, Cypress Bioscience, Lundbeck, Otsuka,
Sunovion, Sanofi-aventis, Takeda, Teva and been a Speaker for
Janssen-Cilag, Otsuka, and Sunovion. Dr. Gold has served as a consultant
to Astra Zeneca, Eli Lilly and Company, Merck and Company, and Pfizer
Pharma. Drs. Heaton and Schoenbaum have no activities to disclose.
NR 72
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U2 34
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 2012
VL 140
IS 1-3
BP 1
EP 8
DI 10.1016/j.schres.2012.03.025
PG 8
WC Psychiatry
SC Psychiatry
GA 996FK
UT WOS:000308070000001
PM 22503642
ER
PT J
AU Harvey, PD
Heaton, RK
Carpenter, WT
Green, MF
Gold, JM
Schoenbaum, M
AF Harvey, Philip D.
Heaton, Robert K.
Carpenter, William T., Jr.
Green, Michael F.
Gold, James M.
Schoenbaum, Michael
TI Diagnosis of schizophrenia: Consistency across information sources and
stability of the condition
SO SCHIZOPHRENIA RESEARCH
LA English
DT Review
DE Diagnosis; Disability
ID RELIABILITY; DISORDERS; PSYCHOSIS; COHORT; SYSTEM
AB Background: The Social Security Administration is considering whether schizophrenia may warrant inclusion in their new "Compassionate Allowance" process, which aims to identify diseases and other medical conditions that almost always qualify for Social Security disability benefits simply on the basis of their confirmed presence. This paper examines the reliability and validity of schizophrenia diagnosis, how a valid diagnosis is established, and the stability of the diagnosis over time. A companion paper summarizes evidence on the empirical association between schizophrenia and disability, thus leading to this paper that evaluates how valid clinical diagnoses of schizophrenia are.
Methods: Literature review and synthesis, based on a workplan developed in an expert meeting convened by the National Institute of Mental Health and the Social Security Administration.
Findings: At least since the introduction of the 3rd edition of the American Psychiatric Association's Diagnostic and Statistical Manual (DSM-III) in 1980, diagnoses of schizophrenia made by mental health specialists are valid, reliable, and stable over time, across community as well as academic practice settings, and across different assessment methods. These analyses are particularly valid during the time-frame relevant to social security awards: at least 2 years after the initial stages of illness. We could not find studies that have evaluated the validity or reliability of schizophrenia diagnoses made exclusively by primary care providers (vs. mental health professionals).
Discussion: In the post-DSM-III era, schizophrenia diagnosis-using modern diagnostic criteria-is valid and reliable when performed by doctoral-level mental health specialists (i.e., psychiatrists and psychologists), in community as well as academic settings. (C) 2012 Elsevier B. V. All rights reserved.
C1 [Harvey, Philip D.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Heaton, Robert K.] UCSD Med Ctr, San Diego, CA USA.
[Carpenter, William T., Jr.; Gold, James M.] Maryland Psychiat Res Inst, Catonsville, MD USA.
[Green, Michael F.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Schoenbaum, Michael] NIMH, Rockville, MD 20857 USA.
RP Harvey, PD (reprint author), Univ Miami, Miller Sch Med, 1120 NW 14th St,Suite 1450, Miami, FL 33136 USA.
EM pharvey@med.miami.edu
FU National Institute of Mental Health; Abbott Labs; Genentech; Johnson and
Johnson; Pharma Neuroboost; Roche Pharma; Shire Pharma; Sunovion Pharma;
Takeda Pharma; Bristol Myers Squibb; Eli Lilly and Company; Lundbeck
Pharma; Merck and Company
FX This research was funded by the National Institute of Mental Health, who
provided no input into the reviews conducted and presentation of these
data.; Dr. Harvey has received consulting fees from Abbott Labs,
Genentech, Johnson and Johnson, Pharma Neuroboost, Roche Pharma, Shire
Pharma, Sunovion Pharma, and Takeda Pharma.; Dr. Carpenter has received
consulting fees from Bristol Myers Squibb, Eli Lilly and Company,
Lundbeck Pharma, and Merck and Company.
NR 19
TC 5
Z9 5
U1 7
U2 17
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 2012
VL 140
IS 1-3
BP 9
EP 14
DI 10.1016/j.schres.2012.03.026
PG 6
WC Psychiatry
SC Psychiatry
GA 996FK
UT WOS:000308070000002
PM 22503641
ER
PT J
AU Insel, TR
AF Insel, Thomas R.
TI Compassionate allowance for people with schizophrenia?
SO SCHIZOPHRENIA RESEARCH
LA English
DT Editorial Material
DE Schizophrenia; Disability; Cognition
C1 NIMH, NIH, Bethesda, MD 20892 USA.
RP Insel, TR (reprint author), NIMH, NIH, Bethesda, MD 20892 USA.
EM insel@mail.nih.gov
NR 0
TC 1
Z9 1
U1 0
U2 0
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 2012
VL 140
IS 1-3
BP 15
EP 16
DI 10.1016/j.schres.2012.04.011
PG 2
WC Psychiatry
SC Psychiatry
GA 996FK
UT WOS:000308070000003
PM 22835805
ER
PT J
AU Gogtay, N
Weisinger, B
Bakalar, JL
Stidd, R
de la Vega, OF
Miller, R
Clasen, L
Greenstein, D
Rapoport, JL
AF Gogtay, Nitin
Weisinger, Brian
Bakalar, Jennifer L.
Stidd, Reva
de la Vega, Oscar Fernandez
Miller, Rachel
Clasen, Liv
Greenstein, Deanna
Rapoport, Judith L.
TI Psychotic symptoms and gray matter deficits in clinical pediatric
populations
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE Adolescence; Psychosis; Brain imaging; Schizophrenia; Gray matter;
Pediatrics
ID CHILDHOOD-ONSET SCHIZOPHRENIA; CORTICAL BRAIN-DEVELOPMENT; LONGITUDINAL
MRI; BIPOLAR DISORDER; COMMUNITY SAMPLE; CHRONIC EXPOSURE; MACAQUE
MONKEYS; ABNORMALITIES; CHILDREN; VOLUME
AB Background: Neuroanatomic studies have not yet addressed how subtle phenotypic distinctions in psychosis alter the underlying brain changes, and whether there is evidence for psychosis as a dimensional construct. We explored the relationship of cortical GM thickness to psychotic phenotypes in children.
Methods: Cross-sectional comparison of anatomic brain imaging between patients referred as childhood-onset schizophrenia (COS) but ruled out after a drug free inpatient observation. Groups included: patients with no evidence of psychosis (n = 22) after drug free observation, patients with psychosis not otherwise specified (PNOS; total n = 29) further divided into those without other axis I diagnoses (n = 13) and those with other axis I comorbidities (n = 16), age/sex matched COS patients (n = 48), and 51 matched healthy controls. GM cortical thickness was compared between the groups, and regressed on patients' SAPS, SANS and GAS scores.
Results: Patients with no evidence of psychosis showed no cortical GM deficits. Presence of psychosis (PNOS with or without co-morbidities) showed some areas of temporal and prefrontal deficits, more subtle compared to the extensive bilateral cortical deficits seen for COS. GAS SAPS and SANS scores showed a relationship with cortical GM thickness although it did not survive adjustment for multiple comparisons.
Conclusions: These results highlight the need for careful phenotypic characterization, as subtle diagnostic distinctions appear to reflect distinct underlying patterns of brain deficits. The incremental nature of cortical deficits from no psychosis to PNOS to COS may further support dimensional model for psychosis. Published by Elsevier B.V.
C1 [Gogtay, Nitin] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA.
RP Gogtay, N (reprint author), NIMH, Child Psychiat Branch, NIH, Bldg 10,Rm 3N202,10 Ctr Dr, Bethesda, MD 20892 USA.
EM gogtayn@mail.nih.gov
FU NIMH
FX NIMH intramural funding.
NR 52
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U1 5
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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 2012
VL 140
IS 1-3
BP 149
EP 154
DI 10.1016/j.schres.2012.07.006
PG 6
WC Psychiatry
SC Psychiatry
GA 996FK
UT WOS:000308070000026
PM 22835806
ER
PT J
AU de Oliveira, AD
Lima, LG
Mariano-Oliveira, A
Machado, DE
Nasciutti, LE
Andersen, JF
Petersen, LC
Francischetti, IMB
Monteiro, RQ
AF de Oliveira, Andreia Da Silva
Lima, Luize G.
Mariano-Oliveira, Andrea
Machado, Daniel E.
Nasciutti, Luiz E.
Andersen, John F.
Petersen, Lars C.
Francischetti, Ivo M. B.
Monteiro, Robson Q.
TI Inhibition of tissue factor by ixolaris reduces primary tumor growth and
experimental metastasis in a murine model of melanoma
SO THROMBOSIS RESEARCH
LA English
DT Article
DE Tissue factor; melanoma; ixolaris; angiogenesis; metastasis;
anticoagulant therapy
ID PROTEASE-ACTIVATED RECEPTOR-1; HIGHLY PROCOAGULANT PATTERN;
HEPARIN-BINDING EXOSITE; FACTOR EXPRESSION; FACTOR-XA; FACTOR-VIIA;
CELL-LINES; SPECIES COMPATIBILITY; PULMONARY METASTASIS;
MALIGNANT-MELANOMA
AB Melanoma is a highly metastatic cancer and there is strong evidence that the clotting initiator protein, tissue factor (TF), contributes to its aggressive pattern. TF inhibitors may attenuate primary tumor growth and metastasis. In this study, we evaluated the effect of ixolaris, a TF inhibitor, on a murine model of melanoma B16F10 cells. Enzymatic assays performed with B16F10 and human U87-MG tumor cells as the TF source showed that ixolaris inhibits the generation of FX in either murine, human or hybrid FVIIa/TF complexes. The effect of ixolaris on the metastatic potential was further estimated by intravenous injection of B16F10 cells in C57BL/6 mice. Ixolaris (250 mu g/kg) dramatically decreased the number of pulmonary tumor nodules (4 +/- 1 compared to 47 +/- 10 in the control group). Furthermore, a significant decrease in tumor weights was observed in primary tumor growth assays in animals treated with ixolaris (250 mu g/kg) from days 3 to 18 after a subcutaneous inoculation of melanoma cells. Remarkably, immunohistochemical analyses showed that inhibition of melanoma growth by ixolaris is accompanied by a significant downregulation of both vascular endothelial growth factor (VEGF) expression and microvascular density in the tumor mass. Our data demonstrate that ixolaris targets B16F10 cell-derived TF, resulting in the reduction of both the primary tumor growth and the metastatic potential of melanoma, as well as the inhibition of tumor angiogenesis. Therefore TF may be a potential target for the treatment of this aggressive malignancy. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Monteiro, Robson Q.] Univ Fed Rio de Janeiro, CCS, Inst Bioquim Med, Ilha Fundao, BR-21941590 Rio de Janeiro, Brazil.
[Machado, Daniel E.; Nasciutti, Luiz E.] Univ Fed Rio de Janeiro, Inst Ciencias Biomed, BR-21941590 Rio de Janeiro, Brazil.
[Andersen, John F.; Francischetti, Ivo M. B.] NIH, Vector Biol Sect, Bethesda, MD 20892 USA.
[Petersen, Lars C.] Biopharmaceut Res Unit, Novo Nordisk, Maalov, Denmark.
RP Monteiro, RQ (reprint author), Univ Fed Rio de Janeiro, CCS, Inst Bioquim Med, Ilha Fundao, Ave Carlos Chagas Filho 373, BR-21941590 Rio de Janeiro, Brazil.
EM robsonqm@bioqmed.ufrj.br
RI PCM, PG/D-1034-2013; Inbeb, Inct/K-2317-2013; Monteiro,
Robson/B-8007-2014
FU Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq);
Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro Carlos Chagas
Filho (FAPERJ); Fundacao do Cancer; Coordenacao de Aperfeicoamento de
Pessoal de Nivel Superior (CAPES); Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health (NIH)
FX We would like to thank Jorgeane Freire e Souza for her technical
assistance. This research was supported by Conselho Nacional de
Desenvolvimento Cientifico e Tecnologico (CNPq), Fundacao de Amparo a
Pesquisa do Estado do Rio de Janeiro Carlos Chagas Filho (FAPERJ),
Fundacao do Cancer and Coordenacao de Aperfeicoamento de Pessoal de
Nivel Superior (CAPES). This work was supported in part by the
Intramural Research Program of the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health (NIH). Because JFA and IMBF are government
employees and this is a government project, the work is in the public
domain in the United States. Notwithstanding any other agreements, the
NIH reserves the right to provide the work to PubMedCentral for display
and use by the public, and PubMedCentral may tag or modify the work
consistent with its customary practices. You can establish rights
outside of the U.S. subject to a government use license.
NR 55
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U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0049-3848
J9 THROMB RES
JI Thromb. Res.
PD SEP
PY 2012
VL 130
IS 3
BP E163
EP E170
DI 10.1016/j.thromres.2012.05.021
PG 8
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 996IQ
UT WOS:000308078800026
ER
PT J
AU Fisher, VR
David-Ocampo, V
Byrne, KM
Khuu, H
Stroncek, DF
AF Fisher, V. R.
David-Ocampo, V.
Byrne, K. M.
Khuu, H.
Stroncek, D. F.
TI Analysis of the Recovery of Cryopreserved and Thawed CD34 and CD3 Cells
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting and CTTXPO
CY OCT 06-09, 2012
CL Boston, MA
SP AABB, CTTXPO
C1 [Fisher, V. R.; David-Ocampo, V.; Byrne, K. M.; Khuu, H.; Stroncek, D. F.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
EM jenny.fisher@nih.gov
NR 0
TC 0
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U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2012
VL 52
SU 3
SI SI
BP 39A
EP 39A
PG 1
WC Hematology
SC Hematology
GA 000PH
UT WOS:000308398600074
ER
PT J
AU Jackman, RP
Bolgiano, D
Schechterly, CA
Utter, GH
Operskalski, E
Deng, X
Alter, H
Busch, MP
Slichter, SJ
Norris, PJ
AF Jackman, R. P.
Bolgiano, D.
Schechterly, C. A.
Utter, G. H.
Operskalski, E.
Deng, X.
Alter, H.
Busch, M. P.
Slichter, S. J.
Norris, P. J.
TI Levels of HLA Antibodies Measured Using A High Sensitivity Detection
System Do Not Predict Platelet Transfusion Refractoriness Among
Lymphocytotoxicity Assay Negative Subjects
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting and CTTXPO
CY OCT 06-09, 2012
CL Boston, MA
SP AABB, CTTXPO
C1 [Jackman, R. P.; Utter, G. H.; Deng, X.; Busch, M. P.; Norris, P. J.] Blood Syst Res Inst, San Francisco, CA USA.
[Bolgiano, D.; Slichter, S. J.] Puget Sound Blood Ctr, Seattle, WA 98104 USA.
[Schechterly, C. A.; Alter, H.] NIH, Bethesda, MD 20892 USA.
[Utter, G. H.] Univ Calif Davis, Davis, CA 95616 USA.
[Operskalski, E.] Univ So Calif, Los Angeles, CA USA.
[Busch, M. P.; Norris, P. J.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
EM RJackman@bloodsystems.org
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 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2012
VL 52
SU 3
SI SI
BP 49A
EP 49A
PG 1
WC Hematology
SC Hematology
GA 000PH
UT WOS:000308398600098
ER
PT J
AU Tatari-Calderone, Z
Fasano, RM
Pinto, LA
Luban, NL
Vukmanovic, S
AF Tatari-Calderone, Z.
Fasano, R. M.
Pinto, L. A.
Luban, N. L.
Vukmanovic, S.
TI Cytokine Storm in Patients With SCD is Not Predictive of RBC
Alloimmunization
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting and CTTXPO
CY OCT 06-09, 2012
CL Boston, MA
SP AABB, CTTXPO
C1 [Tatari-Calderone, Z.; Vukmanovic, S.] Childrens Natl Med Ctr, Sheikh Zayed Inst Pediat Surg Innovat, Washington, DC 20010 USA.
[Pinto, L. A.] NCI, SAIC Frederick Inc, HPV Immunol Lab, Frederick, MD 21701 USA.
EM ztatari@cnmc.org
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 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2012
VL 52
SU 3
SI SI
BP 135A
EP 136A
PG 2
WC Hematology
SC Hematology
GA 000PH
UT WOS:000308398600321
ER
PT J
AU Beaulieu, GP
Ward, DC
Lee-Stroka, A
Leitman, SF
Flegel, WA
AF Beaulieu, G. P.
Ward, D. C.
Lee-Stroka, A.
Leitman, S. F.
Flegel, W. A.
TI Near Fatal Immune Hemolysis Following a Minor ABO Mismatched Peripheral
Blood Stem Cell Transplant
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting and CTTXPO
CY OCT 06-09, 2012
CL Boston, MA
SP AABB, CTTXPO
C1 [Beaulieu, G. P.; Ward, D. C.; Lee-Stroka, A.; Leitman, S. F.; Flegel, W. A.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
EM gpbeaulieu@gmail.com
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 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2012
VL 52
SU 3
SI SI
BP 139A
EP 139A
PG 1
WC Hematology
SC Hematology
GA 000PH
UT WOS:000308398600330
ER
PT J
AU O'Donghaile, D
Yau, YC
Pogue, S
Kelley, WE
Bolan, CD
Leitman, SF
AF O'Donghaile, D.
Yau, Y. C.
Pogue, S.
Kelley, W. E.
Bolan, C. D.
Leitman, S. F.
TI Predictors of Peripheral Blood Progenitor Cell Mobilization in an
Unrelated-Donor Population
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting and CTTXPO
CY OCT 06-09, 2012
CL Boston, MA
SP AABB, CTTXPO
C1 [O'Donghaile, D.; Yau, Y. C.; Pogue, S.; Kelley, W. E.; Leitman, S. F.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Bolan, C. D.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
EM diarmaid@hematology.ie
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 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2012
VL 52
SU 3
SI SI
BP 180A
EP 180A
PG 1
WC Hematology
SC Hematology
GA 000PH
UT WOS:000308398600439
ER
PT J
AU Tremblay, CA
Uribe, MR
Peaceman, D
Salit, RB
Pavletic, S
Adams, SD
Flegel, WA
AF Tremblay, C. A.
Uribe, M. R.
Peaceman, D.
Salit, R. B.
Pavletic, S.
Adams, S. D.
Flegel, W. A.
TI Graft Versus Host Disease and Minor Histocompatibility Antigens in
Unrelated Peripheral Blood Stem Cell Transplants
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting and CTTXPO
CY OCT 06-09, 2012
CL Boston, MA
SP AABB, CTTXPO
C1 [Tremblay, C. A.; Uribe, M. R.; Adams, S. D.; Flegel, W. A.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
[Peaceman, D.; Salit, R. B.; Pavletic, S.] NCI, NIH, Bethesda, MD 20892 USA.
EM chtrembl@vt.edu
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 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2012
VL 52
SU 3
SI SI
BP 181A
EP 182A
PG 2
WC Hematology
SC Hematology
GA 000PH
UT WOS:000308398600443
ER
PT J
AU Sheldon, S
Paige, TD
Bakker, GR
Berkner, D
Flegel, WA
AF Sheldon, S.
Paige, T. D.
Bakker, G. R.
Berkner, D.
Flegel, W. A.
TI Process Improvement: Detecting Abnormal Appearance of Blood Components
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting and CTTXPO
CY OCT 06-09, 2012
CL Boston, MA
SP AABB, CTTXPO
C1 [Sheldon, S.; Paige, T. D.; Bakker, G. R.; Berkner, D.; Flegel, W. A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
EM ssheldon@cc.nih.gov
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 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2012
VL 52
SU 3
SI SI
BP 232A
EP 233A
PG 2
WC Hematology
SC Hematology
GA 000PH
UT WOS:000308398600571
ER
PT J
AU Gee, A
Silberstein, L
Armant, M
Couture, LA
Wagner, J
McKenna, D
Hei, D
Welniak, L
Lindblad, R
Wood, D
AF Gee, A.
Silberstein, L.
Armant, M.
Couture, L. A.
Wagner, J.
McKenna, D.
Hei, D.
Welniak, L.
Lindblad, R.
Wood, D.
TI Production Assistance for Cellular Therapies (PACT): An Eight-Year
Experience from the United States National Heart, Lung, and Blood
Institute (NHLBI) Contract Research Program in Cell and Tissue Therapies
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting and CTTXPO
CY OCT 06-09, 2012
CL Boston, MA
SP AABB, CTTXPO
C1 [Gee, A.] Baylor Coll Med, Houston, TX 77030 USA.
[Silberstein, L.; Armant, M.] Ctr Human Cell Therapy, Boston, MA USA.
[Couture, L. A.] City Hope Natl Med Ctr, Duarte, CA USA.
[Wagner, J.; McKenna, D.] Univ Minnesota, Minneapolis, MN USA.
[Hei, D.] Univ Wisconsin, Madison, WI USA.
[Welniak, L.] NHLBI, Bethesda, MD 20892 USA.
[Lindblad, R.; Wood, D.] EMMES Corp, Rockville, MD USA.
EM apgee@txch.org
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2012
VL 52
SU 3
SI SI
BP 254A
EP 254A
PG 1
WC Hematology
SC Hematology
GA 000PH
UT WOS:000308398600632
ER
PT J
AU Sheliga, BM
Quaia, C
Cumming, BG
FitzGibbon, EJ
AF Sheliga, B. M.
Quaia, C.
Cumming, B. G.
FitzGibbon, E. J.
TI Spatial summation properties of the human ocular following response
(OFR): Dependence upon the spatial frequency of the stimulus
SO VISION RESEARCH
LA English
DT Article
DE Visual motion; Averaging; Inhibition; Normalization
ID BEHAVIORAL RECEPTIVE-FIELD; VERGENCE EYE-MOVEMENTS; MACAQUE V1 NEURONS;
VISUAL AREA MT; MOTION DETECTORS; ENERGY; CORTEX; NORMALIZATION;
MONKEYS; CELLS
AB Ocular following responses (OFRs) are the initial tracking eye movements that can be elicited at ultra-short latency by sudden motion of a textured pattern. The OFR magnitude depends upon stimulus size, and also upon the spatial frequency (SF) of sine-wave gratings. Here we investigate the interaction of size and SF. We recorded initial OFRs in human subjects when 1D vertical sine-wave gratings were subject to horizontal motion. Gratings were restricted to elongated horizontal apertures-"strips"-aligned with the axis of motion. In Experiment 1 the SF and the height of a single strip was manipulated. The magnitude of the OFR increased with strip height up to some optimum value, while strip heights greater than this optimum produced smaller responses. This effect was strongly dependent on SF: the optimum strip height was smaller for higher SFs. In order to explore the underlying mechanism, Experiment 2 measured OFRs to stimuli composed of two thin horizontal strips-one in the upper visual field, the other in the lower visual field-whose vertical separation varied 32-fold. Stimuli of different sizes can be reconstructed from the sum of such horizontal strips. We found that the OFRs in Experiment 1 were smaller than the sum of the responses to the component stimuli, but greater than the average of those responses. We defined an averaging coefficient that described whether a given response was closer to the sum or to the average. For any one SF, the averaging coefficients were similar over a wide range of stimulus sizes, while they varied considerably (7-fold) for stimuli of different SFs. Published by Elsevier Ltd.
C1 [Sheliga, B. M.; Quaia, C.; Cumming, B. G.; FitzGibbon, E. J.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
RP Sheliga, BM (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Room 2A50,49 Convent Dr, Bethesda, MD 20892 USA.
EM bms@lsr.nei.nih.gov
FU Intramural Research Program of the National Eye Institute at the
National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Eye Institute at the National Institutes of Health.
NR 37
TC 6
Z9 6
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0042-6989
J9 VISION RES
JI Vision Res.
PD SEP 1
PY 2012
VL 68
BP 1
EP 13
DI 10.1016/j.visres.2012.07.006
PG 13
WC Neurosciences; Ophthalmology
SC Neurosciences & Neurology; Ophthalmology
GA 002HH
UT WOS:000308522200001
PM 22819728
ER
PT J
AU Shebl, FM
Engels, EA
Goedert, JJ
AF Shebl, Fatma M.
Engels, Eric A.
Goedert, James J.
TI Opportunistic Intestinal Infections and Risk of Colorectal Cancer Among
People with AIDS
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID SQUAMOUS-CELL CARCINOMA; ACQUIRED-IMMUNODEFICIENCY-SYNDROME;
HERPES-SIMPLEX VIRUS-2; UNITED-STATES; HUMAN-PAPILLOMAVIRUS;
HIV-INFECTION; RECTUM; CRYPTOSPORIDIOSIS; ADENOCARCINOMA; COLONOSCOPY
AB Because mucosal inflammation contributes to colorectal carcinogenesis, we studied the impact of intestinal infections on risk of this malignancy among people with AIDS (PWA). Using the population-based HIV/AIDS Cancer Match, which includes approximately half of all PWA in the United States, the cancer registries ascertained colorectal cancers (ICD-O3 codes C180-C189, C199, C209, and C260). During 4-120 months after AIDS onset, risk of cancer occurring after AIDS-defining intestinal infections (considered as time-dependent exposures) was estimated with hazard ratios (HR) and 95% confidence intervals (CI) calculated by Cox regression. Analyses included cancers overall and by histology and anatomic site. After excluding 118 squamous cell rectal cancers (possible anal cancers), we analyzed 320 incident colorectal cancer cases that occurred among 471,909 PWA. Colorectal cancer risk was marginally elevated following cryptosporidiosis (HR = 2.08, 95% CI = 0.93-4.70, p=0.08) and mucocutaneous herpes (HR = 1.69, 95% CI = 0.97-2.95, p=0.07) but not with Pneumocystis pneumonia (HR = 0.79, 95% CI = 0.57-1.10). Cryptosporidiosis was associated with rare colon squamous cell carcinoma [N=8, HR = 13, 95% CI = 1.5-110] and uncommon histologies [HR = 4.4, 95% CI = 1.1-18, p=0.04], but it was not associated with colorectal adenocarcinoma (N=269, HR = 1.3, 95% CI = 0.4-3.9, p = 0.70). Mucocutaneous herpes was associated with colon squamous cell carcinoma (HR = 13, 95% CI = 2.4-67, p=0.003) but not with colorectal adenocarcinoma (HR = 1.3, 95% CI=0.6-2.6, p=0.52) or uncommon histologies (HR = 2.5, 95% CI = 0.8-8.2, p=0.13). Colon squamous cell carcinoma risk was significantly elevated among PWA who had cryptosporidiosis or mucocutaneous herpes. These findings might suggest that HPV or inflammation from other infection may contribute to carcinogenesis.
C1 [Shebl, Fatma M.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA.
RP Shebl, FM (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 7074, Rockville, MD 20852 USA.
EM sheblf@mail.nih.gov
FU National Cancer Institute
FX This research was supported by the Intramural Research Program of the
National Cancer Institute. The authors thank the staff at the following
HIV/AIDS and cancer registries for providing the data for the HIV/AIDS
Cancer Match Study: Colorado, Connecticut, Florida, Georgia, Illinois,
Los Angles, Maryland, Massachusetts, Michigan, New Jersey, New York
City, San Diego, San Francisco, Seattle, Texas, and Washington, DC.
NR 45
TC 1
Z9 1
U1 1
U2 2
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 2012
VL 28
IS 9
BP 794
EP 799
DI 10.1089/aid.2011.0185
PG 6
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 999TG
UT WOS:000308337300006
ER
PT J
AU Mullis, CE
Oliver, AE
Eller, LA
Guwatudde, D
Mueller, AC
Eller, MA
Kibuuka, H
Robb, M
Quinn, TC
Redd, AD
AF Mullis, Caroline E.
Oliver, Amy E.
Eller, Leigh Anne
Guwatudde, David
Mueller, Amy C.
Eller, Michael A.
Kibuuka, Hannah
Robb, Merlin
Quinn, Thomas C.
Redd, Andrew D.
TI Short Communication Colony-Forming Hematopoietic Progenitor Cells Are
Not Preferentially Infected by HIV Type 1 Subtypes A and D in Vivo
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS-INFECTION; HUMAN-BONE-MARROW; RESERVOIRS; STEM
AB HIV subtype C has previously been shown to infect hematopoietic progenitor cells (HPCs) at a significantly higher rate than subtype B. To better understand the subtype-specific nature of HPC infection, we examined the prevalence of HPC infection in vivo by HIV-1 subtypes A and D. HIV-1 infection of HPC was examined in 40 individuals, 19 infected with subtype A and 21 with subtype D, using a single colony assay format. DNA from 1177 extracted colonies was tested for integrated viral DNA of the p24 gene. Four colonies were found to be stably infected, three of 462 colonies (0.65%) from HIV-1A-infected individuals (1/19 individuals) and one of 715 colonies (0.14%) from HIV-1D-infected individuals (1/22 individuals). These rates of colony infection were comparable to the rates observed in PBMCs from the same subjects. Additionally, no correlation was observed between cell colony density and circulating viral load or proviral load. Our findings suggest that HIV-1 subtypes A and D do not preferentially infect colony-forming HPCs over mature HIV target cells in vivo.
C1 [Quinn, Thomas C.; Redd, Andrew D.] NIAID, Div Intramural Res, NIH, Baltimore, MD 21205 USA.
[Mullis, Caroline E.; Oliver, Amy E.; Mueller, Amy C.; Quinn, Thomas C.] Johns Hopkins Univ, Johns Hopkins Med Inst, Baltimore, MD USA.
[Eller, Leigh Anne; Eller, Michael A.; Robb, Merlin] US Mil HIV Res Program MHRP, Rockville, MD USA.
[Guwatudde, David; Kibuuka, Hannah] Makerere Univ, Walter Reed Project, Kampala, Uganda.
RP Redd, AD (reprint author), NIAID, Div Intramural Res, NIH, 855 N Wolfe St, Baltimore, MD 21205 USA.
EM aredd2@jhmi.edu
FU Division of Intramural Research, NIAID, NIH; U.S. Military HIV Research
Program
FX The authors would like to thank all the study participants and study
staff. All subjects provided written informed consent for their samples
to be stored and used for future HIV-related research. The study was
approved by the Science and Ethics Committee of the Uganda Virus
Research Institute, the NIH Office of Human Subjects Research, and the
Division of Human Subjects Protection U.S. Army Walter Reed Institute of
Research. There are no conflicting interests for any of the study
authors. The hinders had no role in the study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
This study was supported in part by funding from the Division of
Intramural Research, NIAID, NIH and U.S. Military HIV Research Program.
NR 19
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 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD SEP
PY 2012
VL 28
IS 9
BP 919
EP 923
DI 10.1089/aid.2011.0179
PG 5
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 999TG
UT WOS:000308337300024
ER
PT J
AU Gao, B
AF Gao, B.
TI HEPATOPROTECTION AND THERAPEUTIC POTENTIAL OF INTERLEUKIN-22 IN
ALCOHOLIC LIVER DISEASE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 16th World Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY SEP 09-12, 2012
CL Sapporo, JAPAN
SP Int Soc Biomed Res Alcoholism (ISBRA), Japanese Med Soc Alcohol & Drug Studies (JMSAS), Sci Council Japan
C1 [Gao, B.] NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD SEP
PY 2012
VL 36
SU 2
SI SI
BP 21A
EP 21A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 000OS
UT WOS:000308396700036
ER
PT J
AU Holmes, A
Fitzgerald, PJ
MacPherson, KP
DeBrouse, L
Gunduz-Cinar, O
Camp, M
AF Holmes, A.
Fitzgerald, P. J.
MacPherson, K. P.
DeBrouse, L.
Gunduz-Cinar, O.
Camp, M.
TI EFFECTS OF CHRONIC ALCOHOL ON PREFRONTAL-MEDIATED FEAR REGULATION
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 16th World Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY SEP 09-12, 2012
CL Sapporo, JAPAN
SP Int Soc Biomed Res Alcoholism (ISBRA), Japanese Med Soc Alcohol & Drug Studies (JMSAS), Sci Council Japan
C1 [Holmes, A.; Fitzgerald, P. J.; MacPherson, K. P.; DeBrouse, L.; Gunduz-Cinar, O.; Camp, M.] NIAAA, Lab Behav & Genom Neurosci, Bethesda, MD USA.
RI Gunduz Cinar, Ozge/B-2970-2009
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 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD SEP
PY 2012
VL 36
SU 2
SI SI
BP 29A
EP 29A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 000OS
UT WOS:000308396700068
ER
PT J
AU Zakhari, S
AF Zakhari, S.
TI ALCOHOL AND CANCER: WHAT AND WHY?
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 16th World Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY SEP 09-12, 2012
CL Sapporo, JAPAN
SP Int Soc Biomed Res Alcoholism (ISBRA), Japanese Med Soc Alcohol & Drug Studies (JMSAS), Sci Council Japan
C1 [Zakhari, S.] NIAAA, Div Metab & Hlth Effects, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD SEP
PY 2012
VL 36
SU 2
SI SI
BP 48A
EP 48A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 000OS
UT WOS:000308396700145
ER
PT J
AU Lovinger, DM
Carlson, VCC
Grant, KA
AF Lovinger, D. M.
Carlson, V. C. Cuzon
Grant, K. A.
TI DECREASED INHIBITION IN PUTAMEN IS ASSOCIATED WITH ADOLESCENT-ONSET
EXCESSIVE DRINKING IN PRIMATES
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 16th World Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY SEP 09-12, 2012
CL Sapporo, JAPAN
SP Int Soc Biomed Res Alcoholism (ISBRA), Japanese Med Soc Alcohol & Drug Studies (JMSAS), Sci Council Japan
C1 [Lovinger, D. M.; Carlson, V. C. Cuzon; Grant, K. A.] NIAAA, Lab Integrat Neurosci, Bethesda, MD 20892 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 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD SEP
PY 2012
VL 36
SU 2
SI SI
BP 51A
EP 51A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 000OS
UT WOS:000308396700157
ER
PT J
AU Chou, P
AF Chou, P.
TI BURDEN OF INJURY FROM ALCOHOL IN ASIA - RESULTS FROM THE NEW GLOBAL
BURDEN OF DISEASE STUDY
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 16th World Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY SEP 09-12, 2012
CL Sapporo, JAPAN
SP Int Soc Biomed Res Alcoholism (ISBRA), Japanese Med Soc Alcohol & Drug Studies (JMSAS), Sci Council Japan
C1 [Chou, P.] NIAAA, 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 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD SEP
PY 2012
VL 36
SU 2
SI SI
BP 55A
EP 55A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 000OS
UT WOS:000308396700171
ER
PT J
AU Kimura, M
Zhou, Z
Yuan, Q
Marietta, C
Brooks, PJ
Crabb, DW
Goldman, D
AF Kimura, M.
Zhou, Z.
Yuan, Q.
Marietta, C.
Brooks, P. J.
Crabb, D. W.
Goldman, D.
TI THE EFFECT OF ACETALDEHYDE ON GLOBAL RNA EXPRESSION: TRANSCRIPTOME
ANALYSIS OF HELA CELL LINES WITH/WITHOUT ALDH2
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 16th World Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY SEP 09-12, 2012
CL Sapporo, JAPAN
SP Int Soc Biomed Res Alcoholism (ISBRA), Japanese Med Soc Alcohol & Drug Studies (JMSAS), Sci Council Japan
C1 [Kimura, M.; Zhou, Z.; Yuan, Q.; Marietta, C.; Brooks, P. J.; Crabb, D. W.; Goldman, D.] NIAAA, NIH, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD SEP
PY 2012
VL 36
SU 2
SI SI
BP 112A
EP 112A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 000OS
UT WOS:000308396700387
ER
PT J
AU Ikeda, H
Delagy, AH
Yokogawa, T
Urban, JM
Burgess, HA
Ono, F
AF Ikeda, H.
Delagy, A. H.
Yokogawa, T.
Urban, J. M.
Burgess, H. A.
Ono, F.
TI THE NICOTINIC ACETYLCHOLINE RECEPTOR ANTAGONIST MECAMYLAMINE SUPPRESSES
ALCOHOL-INDUCED ACUTE TOLERANCE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 16th World Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY SEP 09-12, 2012
CL Sapporo, JAPAN
SP Int Soc Biomed Res Alcoholism (ISBRA), Japanese Med Soc Alcohol & Drug Studies (JMSAS), Sci Council Japan
C1 [Ikeda, H.; Delagy, A. H.; Yokogawa, T.; Urban, J. M.; Burgess, H. A.; Ono, F.] NIAAA, Sect Model Synapt Syst, Lab Mol Physiol, NIH, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD SEP
PY 2012
VL 36
SU 2
SI SI
BP 126A
EP 126A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 000OS
UT WOS:000308396700445
ER
PT J
AU Bing, ZY
Li, JH
Master, SR
Lee, CC
Puthiyaveettil, R
Tomaszewski, JE
AF Bing, Zhanyong
Li, Jinhong
Master, Stephen R.
Lee, Chyi-chia
Puthiyaveettil, Raghunath
Tomaszewski, John E.
TI Fluorescence In Situ Hybridization Study of Chromosome Abnormalities of
Upper Urinary Tract Urothelial Carcinoma in Paraffin-Embedded Tissue
SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Article
DE Urothelial carcinoma; Upper urinary tract; FISH; Aneuploidy
ID TRANSITIONAL-CELL CARCINOMA; BLADDER-CANCER; TUMORS; ABERRATIONS;
UTILITY; GRADE
AB Urothelial carcinomas arising from the upper urinary tract (renal pelvis and ureter) are rare and few molecular genetic studies of these tumors have been conducted to date. We investigated hyperploidy at chromosomes 3, 7, and 17 using a multitarget fluorescence in situ hybridization system to identify, genetic alterations in patients with urothelial carcinomas of the upper urinary tract. Chromosomal aberrations are seen most frequently in the high-grade tumors. A highly significant relationship was found between an increase in the percentage of hyperdiploidy and high grade,for each chromosome (chromosome 3, P = 6 x 10(-4); chromosome 7, P = 2 x 10(-4); chromosome 17, P = 6 x 10(-5)). To determine whether these associations were independent for each chromosome, the correlation between percentage of hyperdiploidy for each pair of chromosomes was examined. In each case, the correlation was highly significant (R = 0.89-0.91). No statistically significant association was found between percentage of hyperdiploidy and tumor stage for any chromosome.
C1 [Bing, Zhanyong; Master, Stephen R.; Puthiyaveettil, Raghunath] Hosp Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Li, Jinhong] Geisinger Med Labs, Danville, PA USA.
[Lee, Chyi-chia] NIH, Bethesda, MD 20892 USA.
[Tomaszewski, John E.] SUNY Buffalo, Buffalo, NY 14260 USA.
RP Bing, ZY (reprint author), Hosp Univ Penn, Dept Pathol & Lab Med, 6 Founders,3400 Spruce St, Philadelphia, PA 19104 USA.
EM bingz@uphs.upenn.edu
NR 25
TC 2
Z9 2
U1 0
U2 0
PU AMER SOC CLINICAL PATHOLOGY
PI CHICAGO
PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA
SN 0002-9173
J9 AM J CLIN PATHOL
JI Am. J. Clin. Pathol.
PD SEP
PY 2012
VL 138
IS 3
BP 382
EP 389
DI 10.1309/AJCPUXAP6P2GVBTI
PG 8
WC Pathology
SC Pathology
GA 998SD
UT WOS:000308259800011
PM 22912355
ER
PT J
AU Volkow, ND
Warren, KR
AF Volkow, Nora D.
Warren, Kenneth R.
TI Advancing American Indian/Alaska Native Substance Abuse Research
SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE
LA English
DT Editorial Material
C1 [Volkow, Nora D.] NIDA, NIH, Bethesda, MD 20892 USA.
[Warren, Kenneth R.] NIAAA, NIH, Bethesda, MD USA.
RP Volkow, ND (reprint author), NIDA, NIH, Bethesda, MD 20892 USA.
EM nvolkow@nida.nih.gov
NR 0
TC 1
Z9 1
U1 0
U2 1
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0095-2990
J9 AM J DRUG ALCOHOL AB
JI Am. J. Drug Alcohol Abuse
PD SEP
PY 2012
VL 38
IS 5
BP 371
EP 371
DI 10.3109/00952990.2012.712174
PG 1
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA 996KS
UT WOS:000308086400001
PM 22931067
ER
PT J
AU Etz, KE
Arroyo, JA
Crump, AD
Rosa, CL
Scott, MS
AF Etz, Kathleen E.
Arroyo, Judith A.
Crump, Aria D.
Rosa, Carmen L.
Scott, Marcia S.
TI Advancing American Indian and Alaska Native Substance Abuse Research:
Current Science and Future Directions
SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE
LA English
DT Article
DE substance abuse; American Indian; Alaska Native; drug abuse; alcohol
abuse
ID NATIONAL EPIDEMIOLOGIC SURVEY; UNITED-STATES; ALCOHOL-USE; POPULATIONS;
DISPARITIES; COMORBIDITY; DEPENDENCE; DISABILITY; PREVALENCE; PATTERNS
AB American Indians and Alaska Natives (AI/AN) have disproportionately high rates of substance abuse yet there is little empirical research addressing this significant public health problem. This paper is an introduction to a special issue that includes cutting edge science in this research area. We identify several areas that require consideration in this field and indicate how the papers in the special issue address these gaps. These overarching areas of need, which should be considered in any substantive research, include attention to heterogeneity within the population, research that has tangible health benefits, continued work on research methods and strategies, increased focus on strength based and community oriented approaches, and the need for strong research partnerships. The special issue marks a major step forward for AI/AN substance abuse research. However, articles also highlight where more work is need to improve public health in AI/AN communities by addressing identified gap areas.
C1 [Etz, Kathleen E.; Crump, Aria D.; Rosa, Carmen L.] NIDA, NIH, Bethesda, MD 20892 USA.
[Arroyo, Judith A.; Scott, Marcia S.] NIAAA, NIH, Bethesda, MD USA.
RP Etz, KE (reprint author), NIDA, NIH, 6001 Execut Blvd, Rockville, MD 20892 USA.
EM ketz@nida.nih.gov
NR 31
TC 7
Z9 7
U1 5
U2 18
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0095-2990
J9 AM J DRUG ALCOHOL AB
JI Am. J. Drug Alcohol Abuse
PD SEP
PY 2012
VL 38
IS 5
BP 372
EP 375
DI 10.3109/00952990.2012.712173
PG 4
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA 996KS
UT WOS:000308086400002
PM 22931068
ER
PT J
AU Shah, NN
Bacher, U
Fry, T
Calvo, KR
Stetler-Stevenson, M
Arthur, DC
Kurlander, R
Baird, K
Wise, B
Giralt, S
Bishop, M
Hardy, NM
Wayne, AS
AF Shah, Nirali N.
Bacher, Ulrike
Fry, Terry
Calvo, Katherine R.
Stetler-Stevenson, Maryalice
Arthur, Diane C.
Kurlander, Roger
Baird, Kristin
Wise, Barbara
Giralt, Sergio
Bishop, Michael
Hardy, Nancy M.
Wayne, Alan S.
TI Myelodysplastic syndrome after allogeneic hematopoietic stem cell
transplantation: Diagnostic and therapeutic challenges
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; OF-THE-LITERATURE;
ACUTE LYMPHOBLASTIC-LEUKEMIA; 1ST INTERNATIONAL WORKSHOP; ACUTE
MYELOGENOUS LEUKEMIA; CHILDRENS-ONCOLOGY-GROUP; HIGH-DOSE CHEMOTHERAPY;
DONOR CELLS; INTENSIVE CHEMOTHERAPY
C1 [Shah, Nirali N.; Fry, Terry; Baird, Kristin; Wise, Barbara; Wayne, Alan S.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Bacher, Ulrike] Univ Med Ctr Hamburg Eppendorf, Dept Stem Cell Transplantat, Hamburg, Germany.
[Calvo, Katherine R.; Kurlander, Roger] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Stetler-Stevenson, Maryalice; Arthur, Diane C.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Giralt, Sergio] Mem Sloan Kettering Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapies, New York, NY 10021 USA.
[Bishop, Michael] Med Coll Wisconsin, Dept Stem Cell Transplantat, Milwaukee, WI 53226 USA.
[Bishop, Michael; Hardy, Nancy M.; Wayne, Alan S.] NCI, Expt Transplantat Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Shah, NN (reprint author), NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bldg 10,Room 1W-3750,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM Nirali.Shah@nih.gov
RI Calvo, Katherine/A-8109-2009;
OI Calvo, Katherine/0000-0002-0771-4191
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research; Warren Grant Magnuson Clinical Center
FX Contract grant sponsors: Intramural Research Program of the National
Institutes of Health, National Cancer Institute, Center for Cancer
Research and the Warren Grant Magnuson Clinical Center.
NR 95
TC 2
Z9 2
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0361-8609
J9 AM J HEMATOL
JI Am. J. Hematol.
PD SEP
PY 2012
VL 87
IS 9
BP 916
EP 922
DI 10.1002/ajh.23174
PG 7
WC Hematology
SC Hematology
GA 993FY
UT WOS:000307843300014
PM 22473867
ER
PT J
AU Adegbola, R
Nesin, M
Wairagkar, N
AF Adegbola, Richard
Nesin, Mirjana
Wairagkar, Niteen
TI Immunogenicity and efficacy of influenza immunization during pregnancy:
recent and ongoing studies
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE efficacy; immunogenicity; influenza immunization; pregnancy
AB Pregnant women and young infants are at increased risk from influenza. The World Health Organization and public health guidelines from Australia, Canada, and the United States recommend immunizing pregnant women with trivalent inactivated influenza vaccine. However, there are multiple barriers to the uptake of this recommendation. Additionally, current vaccines are not licensed for infants <6 months of age. Immunizing pregnant women would provide protection to both mothers and infants. The Bill & Melinda Gates Foundation (BMGF) and the National Institute of Allergy and Infectious Diseases (NIAID) are trying to address some of the issues associated with maternal immunization, which could be an effective intervention in both high- and low-resource settings to combat the significant maternal and infant morbidity and mortality due to influenza. BMGF and NIAID efforts are complementary to each other, focusing on evaluating the immunogenicity, efficacy, and safety of influenza vaccines during pregnancy; and the potential effect of maternal immunization on outcomes in infants in low-resource populations.
C1 [Adegbola, Richard; Wairagkar, Niteen] Bill & Melinda Gates Fdn, Seattle, WA USA.
[Nesin, Mirjana] NIAID, NIH, Bethesda, MD 20892 USA.
RP Adegbola, R (reprint author), Bill & Melinda Gates Fdn, Seattle, WA USA.
NR 9
TC 19
Z9 19
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD SEP
PY 2012
VL 207
IS 3
SU S
BP S28
EP S32
DI 10.1016/j.ajog.2012.07.001
PG 5
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 997SC
UT WOS:000308185400006
PM 22920055
ER
PT J
AU Yeh, S
Albini, TA
Moshfeghi, AA
Nussenblatt, RB
AF Yeh, Steven
Albini, Thomas A.
Moshfeghi, Andrew A.
Nussenblatt, Robert B.
TI Uveitis, the Comparison of Age-Related Macular Degeneration Treatments
Trials (CATT), and Intravitreal Biologics for Ocular Inflammation
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Editorial Material
ID BEVACIZUMAB AVASTIN; CHOROIDAL NEOVASCULARIZATION; NONINFECTIOUS
UVEITIS; REFRACTORY UVEITIS; INFLIXIMAB THERAPY; RANIBIZUMAB; DISEASE;
PHARMACOKINETICS; INJECTION; RITUXIMAB
AB PURPOSE: To provide perspective on the implications of the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) on intravitreal biologic agents in uveitis and retinal diseases in which ocular inflammatory pathways are central to their pathogenesis.
DESIGN: Interpretative essay.
METHODS: Literature review and interpretation.
RESULTS: Besides the clear importance of CATT from a patient treatment perspective in age-related macular degeneration (AMD), these data highlight the critical relevance of highly specific protein immunotherapies offered with biologic agents. The CATT trial also provides a reminder regarding the importance of rigorous efficacy and safety monitoring required when administering intravitreal biologic therapy. Within the field of uveitis, systemic and local biologics have been used to effectively treat uveitis, targeting pathways implicated in both angiogenesis and inflammation (eg, tumor necrosis factor-alpha [TNF-alpha] and interleukin-2 pathways), and research on intravitreal biologic therapy for uveitis and AMD will continue to expand. With over 25 ongoing clinical trials on intravitreal biologic therapy for AMD, enthusiasm for vanguard biologic therapies should be tempered by judicious monitoring for adverse events.
CONCLUSION: The importance of the CATT trial encompasses day-to-day treatment decisions for AMD, as well as lessons on how biologics for ocular disease should be implemented into clinical practice. Specifically, the introduction of intravitreal biologic therapies into clinical practice for uveitis, AMD, and other ocular diseases in which inflammation is involved should be guided by a clear understanding of the immunotherapeutic agent and its molecular target and with rigorous monitoring for both patient benefit and patient safety. (Am J Ophthalmol 2012;154:429-435. Published by Elsevier Inc.)
C1 [Nussenblatt, Robert B.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Albini, Thomas A.; Moshfeghi, Andrew A.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA.
[Yeh, Steven] Emory Univ, Sch Med, Emory Eye Ctr, Atlanta, GA USA.
RP Nussenblatt, RB (reprint author), NEI, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM DrBob@nei.nih.gov
OI Albini, Thomas/0000-0003-2199-9047
FU Intramural NIH HHS [ZIA EY000356-11, ZIA EY000464-04, Z01 EY000439-03]
NR 46
TC 6
Z9 7
U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD SEP
PY 2012
VL 154
IS 3
BP 429
EP 435
DI 10.1016/j.ajo.2012.05.011
PG 7
WC Ophthalmology
SC Ophthalmology
GA 996SR
UT WOS:000308115600004
PM 22898344
ER
PT J
AU Tabak, RG
Khoong, EC
Chambers, DA
Brownson, RC
AF Tabak, Rachel G.
Khoong, Elaine C.
Chambers, David A.
Brownson, Ross C.
TI Bridging Research and Practice Models for Dissemination and
Implementation Research
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Review
ID REPLICATING EFFECTIVE PROGRAMS; NORMALIZATION PROCESS THEORY;
HEALTH-SERVICES RESEARCH; KNOWLEDGE TRANSLATION; PUBLIC-HEALTH;
BEHAVIORAL INTERVENTIONS; RESEARCH ORGANIZATIONS; CONCEPTUAL-FRAMEWORK;
TECHNOLOGY-TRANSFER; PREVENTION RESEARCH
AB Context: Theories and frameworks (hereafter called models) enhance dissemination and implementation (D&I) research by making the spread of evidence-based interventions more likely. This work organizes and synthesizes these models by (1) developing an inventory of models used in D&I research; (2) synthesizing this information; and (3) providing guidance on how to select a model to inform study design and execution.
Evidence acquisition: This review began with commonly cited models and model developers and used snowball sampling to collect models developed in any year from journal articles, presentations, and books. All models were analyzed and categorized in 2011 based on three author-defined variables: construct flexibility, focus on dissemination and/or implementation activities (D/I), and the socioecologic framework (SEF) level. Five-point scales were used to rate construct flexibility from broad to operational and D/I activities from dissemination-focused to implementation-focused. All SEF levels (system, community, organization, and individual) applicable to a model were also extracted. Models that addressed policy activities were noted.
Evidence synthesis: Sixty-one models were included in this review. Each of the five categories in the construct flexibility and D/I scales had at least four models. Models were distributed across all levels of the SEF; the fewest models (n=8) addressed policy activities. To assist researchers in selecting and utilizing a model throughout the research process, the authors present and explain examples of how models have been used.
Conclusions: These findings may enable researchers to better identify and select models to inform their D&I work. (Am J Prev Med 2012;43(3):337-350) (C) 2012 American Journal of Preventive Medicine
C1 [Tabak, Rachel G.; Khoong, Elaine C.; Brownson, Ross C.] Washington Univ, Prevent Res Ctr St Louis, Brown Sch, St Louis, MO USA.
[Brownson, Ross C.] Washington Univ, Sch Med, Div Publ Hlth Sci, St Louis, MO USA.
[Brownson, Ross C.] Washington Univ, Alvin J Siteman Canc Ctr, Sch Med, St Louis, MO USA.
[Chambers, David A.] NIMH, NIH, Bethesda, MD 20892 USA.
RP Tabak, RG (reprint author), 660 S Euclid,Campus Box 8109, St Louis, MO 63110 USA.
EM rtabak@wustl.edu
FU CDC, Prevention Research Centers Program [U48/DP001903]; National Cancer
Institute at the NIH [1R01CA124404-01]; National Center for Research
Resources; National Center for Advancing Translational Sciences, NIH
[TL1RR024995, UL1RR024992]
FX This project was funded in part by cooperative agreement number
U48/DP001903 from the CDC, Prevention Research Centers Program, and
Grant 1R01CA124404-01 from the National Cancer Institute at the NIH. It
was also supported in part by the National Center for Research Resources
and the National Center for Advancing Translational Sciences, NIH,
through Grant TL1RR024995 and UL1RR024992. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the NIH.
NR 119
TC 159
Z9 160
U1 14
U2 100
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 2012
VL 43
IS 3
BP 337
EP 350
DI 10.1016/j.amepre.2012.05.024
PG 14
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 993TK
UT WOS:000307882300014
PM 22898128
ER
PT J
AU Weiner, DE
Carpenter, MA
Levy, AS
Ivanova, A
Cole, EH
Hunsicker, L
Kasiske, BL
Kim, SJ
Kusek, JW
Bostom, AG
AF Weiner, D. E.
Carpenter, M. A.
Levy, A. S.
Ivanova, A.
Cole, E. H.
Hunsicker, L.
Kasiske, B. L.
Kim, S. J.
Kusek, J. W.
Bostom, A. G.
TI Kidney Function and Risk of Cardiovascular Disease and Mortality in
Kidney Transplant Recipients: The FAVORIT Trial
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Article
DE Cardiovascular disease; chronic kidney disease; epidemiology; mortality;
glomerular filtration rate; kidney transplant
ID ALL-CAUSE MORTALITY; VASCULAR OUTCOME REDUCTION;
GLOMERULAR-FILTRATION-RATE; RENAL-TRANSPLANTATION; HEART-DISEASE;
FOLIC-ACID; ALBUMINURIA; DYSFUNCTION; CKD; CALCIFICATION
AB In kidney transplant recipients, cardiovascular disease (CVD) is the leading cause of death. The relationship of kidney function with CVD outcomes in transplant recipients remains uncertain. We performed a post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial to assess risk factors for CVD and mortality in kidney transplant recipients. Following adjustment for demographic, clinical and transplant characteristics, and traditional CVD risk factors, proportional hazards models were used to explore the association of estimated GFR with incident CVD and all-cause mortality. In 4016 participants, mean age was 52 years and 20% had prior CVD. Mean eGFR was 49 +/- 18 mL/min/1.73 m(2) . In 3676 participants with complete data, there were 527 CVD events over a median of 3.8 years. Following adjustment, each 5 mL/min/1.73 m(2) higher eGFR at levels below 45 mL/min/1.7 m(2). In conclusion, in stable kidney transplant recipients, lower eGFR is independently associated with adverse events, suggesting that reduced kidney function itself rather than preexisting comorbidity may lead to CVD.
C1 [Weiner, D. E.; Levy, A. S.] Tufts Med Ctr, Boston, MA USA.
[Carpenter, M. A.; Ivanova, A.] Univ N Carolina, Chapel Hill, NC USA.
[Cole, E. H.; Kim, S. J.] Univ Toronto, Toronto, ON M5S 1A1, Canada.
[Hunsicker, L.] Univ Iowa, Coll Med, Iowa City, IA USA.
[Kasiske, B. L.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA.
[Kasiske, B. L.] Univ Minnesota, Minneapolis, MN USA.
[Kusek, J. W.] NIDDK, Bethesda, MD USA.
[Bostom, A. G.] Rhode Isl Hosp, Providence, RI USA.
RP Weiner, DE (reprint author), Tufts Med Ctr, Boston, MA USA.
EM dweiner@tuftsmedicalcenter.org
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health [U01 DK61700]; Office of Dietary
Supplements, NIH; American Society of Nephrology; [K23DK071636]
FX FAVORIT is supported by cooperative agreement U01 DK61700 from the
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health. Dr. Kusek, an employee of the NIDDK, was
involved in the study design, interpretation and writing of the report.
Support also provided by the Office of Dietary Supplements, NIH. PamLab
LLC of Covington, LA provided the high-and low-dose multivitamins. DEW
was supported by K23DK071636 and a Carl Gottschalk Career Development
Award from the American Society of Nephrology.
NR 36
TC 39
Z9 41
U1 3
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-6135
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD SEP
PY 2012
VL 12
IS 9
BP 2437
EP 2445
DI 10.1111/j.1600-6143.2012.04101.x
PG 9
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 994QC
UT WOS:000307945000022
PM 22594581
ER
PT J
AU Markman, B
Tabernero, J
Krop, I
Shapiro, GI
Siu, L
Chen, LC
Mita, M
Cuero, MM
Stutvoet, S
Birle, D
Anak, O
Hackl, W
Baselga, J
AF Markman, B.
Tabernero, J.
Krop, I.
Shapiro, G. I.
Siu, L.
Chen, L. C.
Mita, M.
Cuero, M. Melendez
Stutvoet, S.
Birle, D.
Anak, Oe.
Hackl, W.
Baselga, J.
TI Phase I safety, pharmacokinetic, and pharmacodynamic study of the oral
phosphatidylinositol-3-kinase and mTOR inhibitor BGT226 in patients with
advanced solid tumors
SO ANNALS OF ONCOLOGY
LA English
DT Article
DE anticancer agent; BGT226; dual inhibitor; mTOR catalytic inhibitor; PI3K
pathway; solid tumors
ID ANTITUMOR-ACTIVITY; DOSE-ESCALATION; PI3K PATHWAY; CANCER-CELLS;
RESISTANCE; NVP-BEZ235; MUTATIONS; 3-KINASE; TARGET; TRIALS
AB This phase I dose-escalation study investigated the maximum tolerated dose (MTD), safety, pharmacokinetics, pharmacodynamics (PDs), and preliminary antitumor activity of BGT226, a potent, oral dual phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin inhibitor.
Fifty-seven patients with advanced solid tumors received BGT226 2.5-125 mg/day three times weekly (TIW). Dose escalation was guided by an adaptive Bayesian logistic regression model with overdose control. Assessments included response per RECIST, [18F]-fluorodeoxyglucose uptake, and phosphorylated-S6 in skin and paired tumor samples.
Three patients (125 mg cohort) had dose-limiting toxic effects (grade 3 nausea/vomiting, diarrhea). BGT226-related adverse events included nausea (68%), diarrhea (61%), vomiting (49%), and fatigue (19%). BGT226 demonstrated rapid absorption, variable systemic exposure, and a median half-life of 6-9 h. Seventeen patients (30%) had stable disease (SD) as best response. Nine patients had SD for >= 16 weeks. Thirty patients (53%) achieved stable metabolic disease as assessed by [18F]-fluorodeoxyglucose-positron emission tomography; however, no correlation between metabolic response and tumor shrinkage according to computed tomography was observed. PD changes suggested PI3K pathway inhibition but were inconsistent.
The MTD of BGT226 was 125 mg/day TIW, and the clinically recommended dose was 100 mg/day TIW. Limited preliminary antitumor activity and inconsistent target inhibition were observed, potentially due to low systemic exposure.
C1 [Markman, B.; Tabernero, J.; Baselga, J.] Univ Autonoma Barcelona, Dept Med Oncol, Vall Hebron Univ Hosp, E-08193 Barcelona, Spain.
[Krop, I.; Shapiro, G. I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Siu, L.] Princess Margaret Hosp, Dept Med Oncol & Hematol, Toronto, ON M4X 1K9, Canada.
[Chen, L. C.] NCI, Las Vegas, NV USA.
[Mita, M.] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA.
[Cuero, M. Melendez; Stutvoet, S.; Anak, Oe.; Hackl, W.] Novartis Pharma AG, Oncol Translat Med, Basel, Switzerland.
[Birle, D.] Novartis Inst Biomed Res, Cambridge, MA USA.
RP Baselga, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Hematol & Oncol, 55 Fruit St,Lawrence House 108, Boston, MA 02114 USA.
EM jbaselga@partners.org
FU European Society of Medical Oncology (ESMO); Novartis Pharmaceuticals
Corporation; Novartis Pharma AG
FX We thank the following investigators, Steven Isakoff (Massachussets
General Hospital, Boston, USA), Sunil Sharma (Nevada Cancer Institute,
Las Vegas, USA), Christophe LeTourneau (Princess Margaret Hospital,
Toronto, Canada), and contributors Beatrix Staffler, Humphrey Gardner,
Nina Huseinovic, Nassim Sleiman, Mikael Sacco, Hartmut Zehender, and
Stefan de Buck (Novartis Pharma AG), whose efforts were essential toward
the completion of this work. We would also like to thank the European
Society of Medical Oncology (ESMO) for awarding BM with an ESMO
fellowship grant that contributed to his involvement in this trial. The
authors would also like to acknowledge Dina Marenstein, PhD, of
Chameleon Communications International, who provided medical writing
services with funding from Novartis Pharmaceuticals Corporation.; MMC,
SS, DS, OA, and WH are employees of Novartis Pharma AG, the developer of
BGT226 and the study sponsor. IK receives clinical trial funding from
Novartis Pharma AG. JB has received consulting honoraria from Novartis.
BM, JT, GIS, LS, LCC, and MM have no conflict of interest to declare.
NR 20
TC 58
Z9 58
U1 1
U2 6
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 2012
VL 23
IS 9
BP 2399
EP 2408
DI 10.1093/annonc/mds011
PG 10
WC Oncology
SC Oncology
GA 995NU
UT WOS:000308017000029
PM 22357447
ER
PT J
AU Ko, SU
Stenholm, S
Metter, EJ
Ferrucci, L
AF Ko, Seung-uk
Stenholm, Sari
Metter, E. Jeffrey
Ferrucci, Luigi
TI Age-associated gait patterns and the role of lower extremity strength -
Results from the Baltimore Longitudinal Study of Aging
SO ARCHIVES OF GERONTOLOGY AND GERIATRICS
LA English
DT Article
DE Aging in gait; Adult lifespan; Knee strength; Ankle function; Stride
width
ID OLDER-ADULTS; PHYSICAL FUNCTION; WALKING; SPEED; PERFORMANCE; WOMEN;
DISABILITY; MODELS; ANKLE; YOUNG
AB The aim of the present study was to examine differences in gait characteristics across the adult lifespan and to test the hypothesis that such differences are attributable at least in part to the decline in muscle strength. The data presented here are from 190 participants of the Baltimore Longitudinal Study of Aging (BLSA) aged from 32 to 93 years. Based on two age thresholds that best capture the effect of age on walking speed, participants were divided into three age groups: middle-age (32-57 years; N = 27), old-age (58-78 years; N = 125), and oldest-age (79-93 years; N = 38). Participants were asked to walk at their preferred and maximum speeds while recorded with 3D gait analysis system. In addition, maximum isokinetic knee extensor strength was assessed. While walking at preferred speed, range of motion (ROM) and mechanical work expenditure (MWE) of the ankle were lower within middle-age (p < 0.001, p = 0.047, respectively), while hip ROM and MWE were lower (p = 0.006) and higher (p < 0.001), respectively within oldest-age with older age. Deterioration in ankle function during customary walking initiates already at middle-age. Differences in the maximum walking speed and ankle ROM between middle-age and old-age were explained by knee strength. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Ko, Seung-uk] Chonnam Natl Univ, Dept Mech Engn, Yeosu 550749, Jeonnam, South Korea.
[Stenholm, Sari] Natl Inst Hlth & Welf, Dept Hlth Funct Capac & Welf, Turku, Finland.
[Metter, E. Jeffrey; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
RP Ko, SU (reprint author), Chonnam Natl Univ, Dept Mech Engn, 50 Daehak Ro, Yeosu 550749, Jeonnam, South Korea.
EM seunguk.ko@gmail.com
RI Stenholm, Sari/G-6940-2011
FU Intramural Research Program of the NIH, National Institute on Aging
FX This research was supported entirely by the Intramural Research Program
of the NIH, National Institute on Aging. Data for these analyses were
obtained from the Baltimore Longitudinal Study of Aging, a study
performed by the National Institute on Aging.
NR 27
TC 14
Z9 16
U1 1
U2 8
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0167-4943
J9 ARCH GERONTOL GERIAT
JI Arch. Gerontol. Geriatr.
PD SEP-OCT
PY 2012
VL 55
IS 2
BP 474
EP 479
DI 10.1016/j.archger.2012.04.004
PG 6
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 992YC
UT WOS:000307816300051
PM 22564361
ER
PT J
AU Prescott, J
de Wit, E
Feldmann, H
Munster, VJ
AF Prescott, Joseph
de Wit, Emmie
Feldmann, Heinz
Munster, Vincent J.
TI The immune response to Nipah virus infection
SO ARCHIVES OF VIROLOGY
LA English
DT Review
ID STRAND RNA VIRUSES; PTEROPID BATS; HAMSTER MODEL; HENIPAVIRUS INFECTION;
CLINICAL-FEATURES; SUBUNIT VACCINE; INNATE IMMUNITY; FLYING-FOXES;
W-PROTEINS; IN-VIVO
AB Nipah virus has recently emerged as a zoonotic agent that is highly pathogenic in humans. Outbreaks have occurred regularly over the last two decades in South and Southeast Asia, where mortality rates reach as high as 100 %. The natural reservoir of Nipah virus has been identified as bats from the Pteropus family, where infection is largely asymptomatic. Human disease is characterized by both respiratory and encephalitic components, and thus far, no effective vaccine or intervention strategies are available. Little is know about how the immune response of either the reservoir host or incidental hosts responds to infection, and how this immune response is either inadequate or might contribute to disease in the dead-end host. Experimental vaccines strategies have given us some insight into the immunological requirements for protection. This review summarizes our current understanding of the immune response to Nipah virus infection and emphasizes the need for further research.
C1 [Prescott, Joseph; de Wit, Emmie; Feldmann, Heinz; Munster, Vincent J.] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA.
RP Munster, VJ (reprint author), NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA.
EM Vincent.Munster@nih.gov
OI de Wit, Emmie/0000-0002-9763-7758; Munster, Vincent/0000-0002-2288-3196
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health.
NR 69
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U1 1
U2 13
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 2012
VL 157
IS 9
BP 1635
EP 1641
DI 10.1007/s00705-012-1352-5
PG 7
WC Virology
SC Virology
GA 998IG
UT WOS:000308230500001
PM 22669317
ER
PT J
AU Philpott, CC
Leidgens, S
Frey, AG
AF Philpott, Caroline C.
Leidgens, Sebastien
Frey, Avery G.
TI Metabolic remodeling in iron-deficient fungi
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
LA English
DT Review
DE Aspergillus; Saccharomyces cerevisiae; Schizosaccharomyces pombe; Iron;
Heme; Iron-sulfur cluster
ID YEAST SCHIZOSACCHAROMYCES-POMBE; CCAAT-BINDING COMPLEX; GENOME-WIDE
ANALYSIS; SACCHAROMYCES-CEREVISIAE; GENE-EXPRESSION; TRANSCRIPTION
FACTOR; FISSION YEAST; MESSENGER-RNA; SIDEROPHORE BIOSYNTHESIS;
ASPERGILLUS-FUMIGATUS
AB Eukaryotic cells contain dozens, perhaps hundreds, of iron-dependent proteins, which perform critical functions in nearly every major cellular process. Nutritional iron is frequently available to cells in only limited amounts; thus, unicellular and higher eukaryotes have evolved mechanisms to cope with iron scarcity. These mechanisms have been studied at the molecular level in the model eukaryotes Saccharomyces cerevisiae and Schizosaccharomyces pombe, as well as in some pathogenic fungi. Each of these fungal species exhibits metabolic adaptations to iron deficiency that serve to reduce the cell's reliance on iron. However, the regulatory mechanisms that accomplish these adaptations differ greatly between fungal species. This article is part of a Special Issue entitled: Cell Biology of Metals. Published by Elsevier B.V.
C1 [Philpott, Caroline C.; Leidgens, Sebastien; Frey, Avery G.] NIDDK, Genet & Metab Sect, NIH, Bethesda, MD 20892 USA.
RP Philpott, CC (reprint author), NIDDK, Genet & Metab Sect, NIH, Bldg 10,Rm 9B-16,10 Ctr Dr, Bethesda, MD 20892 USA.
EM carolinep@intra.niddk.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases of NIH
FX The authors are supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases of NIH.
NR 102
TC 39
Z9 40
U1 1
U2 18
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-4889
J9 BBA-MOL CELL RES
JI Biochim. Biophys. Acta-Mol. Cell Res.
PD SEP
PY 2012
VL 1823
IS 9
SI SI
BP 1509
EP 1520
DI 10.1016/j.bbamcr.2012.01.012
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 994GE
UT WOS:000307918100012
PM 22306284
ER
PT J
AU Kasaikina, MV
Hatfield, DL
Gladyshev, VN
AF Kasaikina, Marina V.
Hatfield, Dolph L.
Gladyshev, Vadim N.
TI Understanding selenoprotein function and regulation through the use of
rodent models
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
LA English
DT Review
DE Selenium; Selenocysteine; Selenoprotein; Mouse model
ID SELENOCYSTEINE TRANSFER-RNA; HYDROPEROXIDE GLUTATHIONE-PEROXIDASE;
MITOCHONDRIAL THIOREDOXIN REDUCTASE; TYPE-2 IODOTHYRONINE DEIODINASE;
DISULFIDE BOND FORMATION; TARGETED DISRUPTION; NEUROLOGICAL DYSFUNCTION;
ENDOPLASMIC-RETICULUM; MOLECULAR-MECHANISMS; CONTAINING PROTEINS
AB Selenium (Se) is an essential micronutrient. Its biological functions are associated with selenoproteins, which contain this trace element in the form of the 21st amino acid, selenocysteine. Genetic defects in selenocysteine insertion into proteins are associated with severe health issues. The consequences of selenoprotein deficiency are more variable, with several selenoproteins being essential, and several showing no clear phenotypes. Much of these functional studies benefited from the use of rodent models and diets employing variable levels of Se. This review summarizes the data obtained with these models, focusing on mouse models with targeted expression of individual selenoproteins and removal of individual, subsets or all selenoproteins in a systemic or organ-specific manner. This article is part of a Special Issue entitled: Cell Biology of Metals. (C) 2012 Elsevier By. All rights reserved.
C1 [Kasaikina, Marina V.; Gladyshev, Vadim N.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA.
[Kasaikina, Marina V.; Gladyshev, Vadim N.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Hatfield, Dolph L.] NCI, Lab Canc Prevent, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Gladyshev, VN (reprint author), Brigham & Womens Hosp, Dept Med, Div Genet, New Res Bldg,Room 435,77 Ave Louis Pasteur, Boston, MA 02115 USA.
EM vgladyshev@rics.bwh.harvard.edu
RI Gladyshev, Vadim/A-9894-2013
FU NCI NIH HHS [R01 CA080946, R01 CA080946-12]; NIA NIH HHS [R01 AG021518,
R01 AG021518-11]; NIGMS NIH HHS [R01 GM061603-12, R01 GM061603, R37
GM065204, R37 GM065204-12]
NR 139
TC 32
Z9 35
U1 3
U2 22
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-4889
J9 BBA-MOL CELL RES
JI Biochim. Biophys. Acta-Mol. Cell Res.
PD SEP
PY 2012
VL 1823
IS 9
SI SI
BP 1633
EP 1642
DI 10.1016/j.bbamcr.2012.02.018
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 994GE
UT WOS:000307918100021
PM 22440326
ER
PT J
AU Loland, CJ
Mereu, M
Okunola, OM
Cao, JJ
Prisinzano, TE
Mazier, S
Kopajtic, T
Shi, L
Katz, JL
Tanda, G
Newman, AH
AF Loland, Claus J.
Mereu, Maddalena
Okunola, Oluyomi M.
Cao, Jianjing
Prisinzano, Thomas E.
Mazier, Sonia
Kopajtic, Theresa
Shi, Lei
Katz, Jonathan L.
Tanda, Gianluigi
Newman, Amy Hauck
TI R-Modafinil (Armodafinil): A Unique Dopamine Uptake Inhibitor and
Potential Medication for Psychostimulant Abuse
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Abuse liability; addiction; cocaine; dopamine transporter;
methamphetamine; microdialysis
ID METHAMPHETAMINE DEPENDENCE; DISCRIMINATIVE STIMULUS; TRANSPORTER
OVERLAP; NUCLEUS-ACCUMBENS; BINDING-SITES; DOUBLE-BLIND; COCAINE;
MECHANISM; ALTERS; SINGLE
AB Background: (+/-)-Modafinil has piqued interest as a treatment for attention-deficit/hyperactivity disorder and stimulant dependence. The R-enantiomer of modafinil might have unique pharmacological properties that should be further investigated.
Methods: (+/-)-Modafinil and its R-(-)- and S-(+)-enantiomers were synthesized and tested for inhibition of [H-3] dopamine (DA) uptake and [H-3]WIN 35428 binding in human dopamine transporter (DAT) wild-type and mutants with altered conformational equilibria. Data were compared with cocaine and the atypical DA uptake inhibitor, JHW 007. R- and S-modafinil were also evaluated in microdialysis studies in the mouse nucleus accumbens shell and in a cocaine discrimination procedure.
Results: (+/-)-, R-, and S-modafinil bind to the DAT and inhibit DA uptake less potently than cocaine, with R-modafinil having approximately threefold higher affinity than its S-enantiomer. Molecular docking studies revealed subtle differences in binding modes for the enantiomers. R-modafinil was significantly less potent in the DAT Y156F mutant compared with wild-type DAT, whereas S-modafinil was affected less. Studies with the Y335A DAT mutant showed that the R- and S-enantiomers tolerated the inward-facing conformation better than cocaine, which was further supported by [2-(trimethylammonium)ethyl]-methanethiosulfonate reactivity on the DAT E2C I159C. Microdialysis studies demonstrated that both R- and S-modafinil produced increases in extracellular DA concentrations in the nucleus accumbens shell less efficaciously than cocaine and with a longer duration of action. Both enantiomers fully substituted in mice trained to discriminate cocaine from saline.
Conclusions: R-modafinil displays an in vitro profile different from cocaine. Future trials with R-modafinil as a substitute therapy with the potential benefit of cognitive enhancement for psychostimulant addiction are warranted.
C1 [Okunola, Oluyomi M.; Cao, Jianjing; Newman, Amy Hauck] NIDA, Med Chem Sect, Mol Targets & Medicat Discovery Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
[Loland, Claus J.] Univ Copenhagen, Fac Hlth Sci, Mol Neuropharmacol Lab, Dept Neurosci & Pharmacol, Copenhagen, Denmark.
[Mereu, Maddalena; Kopajtic, Theresa; Katz, Jonathan L.; Tanda, Gianluigi] NIDA, Psychobiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Prisinzano, Thomas E.] Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA.
[Mazier, Sonia; Shi, Lei] Cornell Univ, Weill Med Coll, Dept Physiol & Biophys, New York, NY 10021 USA.
[Mazier, Sonia; Shi, Lei] Cornell Univ, Weill Med Coll, Inst Computat Biomed, New York, NY 10021 USA.
RP Newman, AH (reprint author), NIDA, Med Chem Sect, Mol Targets & Medicat Discovery Branch, Intramural Res Program,NIH, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM anewman@intra.nida.nih.gov
RI Tanda, Gianluigi/B-3318-2009; Loland, Claus/E-5975-2014;
OI Tanda, Gianluigi/0000-0001-9526-9878; Loland, Claus/0000-0002-1773-1446;
Katz, Jonathan/0000-0002-1068-1159
FU National Institute on Drug Abuse Intramural Research Program; Lundbeck
Foundation; Danish Council for Independent Research Sapere Aude
programme
FX Support for this research was provided to AHN, OMO, JC, TK, MM, JLK, and
GT by the National Institute on Drug Abuse Intramural Research Program.
CJL is supported by the Lundbeck Foundation and the Danish Council for
Independent Research Sapere Aude programme.
NR 63
TC 39
Z9 39
U1 2
U2 26
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD SEP 1
PY 2012
VL 72
IS 5
BP 405
EP 413
DI 10.1016/j.biopsych.2012.03.022
PG 9
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 985ZD
UT WOS:000307308100011
PM 22537794
ER
PT J
AU Tewari, P
Martin, PL
Mendizabal, A
Parikh, SH
Page, KM
Driscoll, TA
Malech, HL
Kurtzberg, J
Prasad, VK
AF Tewari, Priti
Martin, Paul L.
Mendizabal, Adam
Parikh, Suhag H.
Page, Kristin M.
Driscoll, Timothy A.
Malech, Harry L.
Kurtzberg, Joanne
Prasad, Vinod K.
TI Myeloablative Transplantation using either Cord Blood or Bone Marrow
leads to Immune Recovery, High Long-Term Donor Chimerism and Excellent
Survival in Chronic Granulomatous Disease
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Chronic granulomatous disease; Cord blood; Myeloablative
ID STEM-CELL TRANSPLANTATION; VERSUS-HOST-DISEASE; OF-THE-LITERATURE;
UNRELATED-DONOR; HEMATOPOIETIC ALLOGRAFT; PEDIATRIC-PATIENTS; GRAFT;
CHILDREN; DIAGNOSIS; OUTCOMES
AB The curative potential of hematopoietic stem cell transplantation in patients with chronic granulomatous disease depends on availability of a suitable donor, successful donor engraftment, and maintenance of long-term donor chimerism. Twelve consecutive children (median age, 59.5 months; range, 8-140 months) with severe chronic granulomatous disease (serious bacterial/fungal infections pretransplantation; median, 3; range, 2-9) received myeloablative hematopoietic stem cell transplantation using sibling bone marrow ([SibBM]; n = 5), unrelated cord blood (UCB; n = 6), and sibling cord blood (n = I) at our center between 1997 and 2010. SibBM and sibling cord blood were HLA matched at 6/6, whereas UCB were 5/6 (n = 5) or 6/6 (n = 1). Recipients of SibBM were conditioned with busulfan and cyclophosphamide anti-thymocyte globulin (ATG), whereas 6 of 7 cord blood recipients received fludarabine/busulfan/cyclophosphamide/ATG. Seven patients received granulocyte-colony stimulating factor-mobilized granulocyte transfusions from directed donors. The first 2 UCB recipients had primary graft failure but successfully underwent retransplantation with UCB. Highest acute graft-versus-host disease was grade III (n = I). Extensive chronic graft-vs-host disease developed in 3 patients. All patients are alive with median follow-up of 70.5 months (range, 12-167 months) with high donor chimerism (>98%, n = 10; 94%, n = I; and 92%, n = I). Myeloablative hematopoietic stem cell transplantation led to correction of neutrophil dysfunction, durable donor chinnerism, excellent survival, good quality of life, and low incidence of graft-vs-host disease regardless of graft source. Biol Blood Marrow Transplant 18: 1368-1377 (2012) Published by Elsevier Inc. on behalf of American Society for Blood and Marrow Transplantation
C1 [Tewari, Priti] Duke Univ, Med Ctr, Pediat Blood & Marrow Transplantat Div, Pediat Blood & Marrow Transplantat Program, Durham, NC 27710 USA.
[Mendizabal, Adam] Emmes Corp, Rockville, MD USA.
[Malech, Harry L.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Tewari, P (reprint author), Duke Univ, Med Ctr, Pediat Blood & Marrow Transplantat Div, Pediat Blood & Marrow Transplantat Program, Box 3350, Durham, NC 27710 USA.
EM priti.tewari@duke.edu
OI Malech, Harry/0000-0001-5874-5775
FU National Heart Lung and Blood Institute of the National Institutes of
Health; Intramural Program of the National Institute of Allergy and
Infectious Diseases, NIH
FX Partial financial support was provided by the National Heart Lung and
Blood Institute of the National Institutes of Health.; Priti Tewari was
involved with conceptualizing the study, collection of clinical data,
analysis of the data, writing of the manuscript, and all the
coordination efforts; Vinod K. Prasad was involved in conceptualizing
the study, analysis of the data, collection of clinical data, editing
the manuscript, and direct contribution in the generation of graft data;
Joanne Kurtzberg was involved in conceptualizing the study, collection
of clinical data, editing the manuscript, and direct contribution in the
generation of graft data; Suhag H. Parikh, Timothy A. Driscoll, Kristin
M. Page, and Paul L. Martin were involved with collection of clinical
data and preparation of the manuscript; Harry L. Malech provided
critical input in preparation and editing of the manuscript and is
supported by the Intramural Program of the National Institute of Allergy
and Infectious Diseases, NIH.
NR 32
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U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD SEP
PY 2012
VL 18
IS 9
BP 1368
EP 1377
DI 10.1016/j.bbmt.2012.02.002
PG 10
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 996VF
UT WOS:000308122200008
PM 22326631
ER
PT J
AU Battiwalla, M
Wang, T
Carreras, J
Deeg, HJ
Ayas, M
Bajwa, RPS
George, B
Gupta, V
Pasquini, R
Schrezenmeier, H
Passweg, JR
Schultz, KR
Eapen, M
AF Battiwalla, Minoo
Wang, Tao
Carreras, Jeanette
Deeg, H. Joachim
Ayas, Mouhab
Bajwa, Rajinder P. S.
George, Biju
Gupta, Vikas
Pasquini, Ricardo
Schrezenmeier, Hubert
Passweg, Jakob R.
Schultz, Kirk R.
Eapen, Mary
TI HLA-Matched Sibling Transplantation for Severe Aplastic Anemia: Impact
of HLA DR15 Antigen Status on Engraftment, Graft-versus-Host Disease,
and Overall Survival
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE DR15; SAA; GVHD; Survival; Graft failure
ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; REDUCED RELAPSE
RATE; MYELODYSPLASTIC SYNDROME; COMPETING RISKS; CHRONIC GVHD;
FREQUENCY; HLA-DR15; FAILURE; DR2
AB The HLA class II DRBI antigen DR15 (common alleles *1501, *1502) is an important marker in the pathobiology of severe aplastic anemia (SAA). We studied 1204 recipients of HLA-matched sibling bone marrow transplantation for SAA to determine whether HLA DR15 status (as determined by allele-level typing) affected hematopoietic recovery, graft-versus-host disease (GVHD), or overall survival (OS). In multivariate analysis, secondary graft failure rate at 2 years was lower in patients who were HLA DR15+ (hazard ratio = 0.46, P =.01). However, neutrophil recovery at day 28, platelet recovery at day 100, acute GVHD, chronic GVHD, and overall mortality were independent of DR15 status. The 5-year probabilities of OS, after adjusting for age, race, performance score, transplant-conditioning regimen, and year of transplantation, were 78% and 81% for patients who were HLA DR15+ and HLA DR15, respectively (P = .35). In conclusion, DR IS status is associated with secondary graft failure after HLA-matched sibling bone marrow transplantation for SAA but has no significant impact on survival. Biol Blood Marrow Transplant IS: 1401-1406 (2012) Published by Elsevier Inc. on behalf of American Society.* Blood and Man-ow Transplantation
C1 [Battiwalla, Minoo] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Wang, Tao; Carreras, Jeanette; Eapen, Mary] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Deeg, H. Joachim] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Ayas, Mouhab] King Faisal Specialist Hosp & Res Ctr, Riyadh 11211, Saudi Arabia.
[Bajwa, Rajinder P. S.] Nationwide Childrens Hosp, Columbus, OH USA.
[George, Biju] Christian Med Coll & Hosp, Vellore 632004, Tamil Nadu, India.
[Gupta, Vikas] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
[Pasquini, Ricardo] UFPR, Hosp Clin, Curitiba, Parana, Brazil.
[Schrezenmeier, Hubert] FU Berlin, Berlin, Germany.
[Passweg, Jakob R.] Hop Cantonal Univ Geneva, Geneva, Switzerland.
[Schultz, Kirk R.] British Columbias Childrens Hosp UBC, Vancouver, BC, Canada.
RP Battiwalla, M (reprint author), NHLBI, Hematol Branch, NIH, 10 CRC,Rm 5-3581,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM minoo.battiwalla@nih.gov
RI Bajwa, Rajinder/J-4304-2014
FU NIH, NHLBI; Public Health Service Grant/Cooperative Agreement from the
National Cancer Institute (NCI) [U24-CA76518]; National Heart, Lung and
Blood Institute (NIMBI); National Institute of Allergy and Infectious
Diseases (MAID); NHLBI [5U01HL069294]; NCI; Health Resources and
Services Administration (HRSA/DHHS); Office of Naval Research
[N00014-06-1-0704, N00014-08-1-0058]; Allos, Inc.; Amgen, Inc.;
[HHSH234200637015C]
FX This research was supported (in part) by the Intramural Research Program
of the NIH, NHLBI; Public Health Service Grant/Cooperative Agreement
U24-CA76518 from the National Cancer Institute (NCI), the National
Heart, Lung and Blood Institute (NIMBI) and the National Institute of
Allergy and Infectious Diseases (MAID); a Grant/Cooperative Agreement
5U01HL069294 from NHLBI and NCI; a contract HHSH234200637015C with
Health Resources and Services Administration (HRSA/DHHS); 2 Grants
N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval Research;
and grants from Allos, Inc.; Amgen, Inc.; Angioblast; Anonymous donation
to the Medical College of Wisconsin; Ariad; Be the Match Foundation;
Blue Cross and Blue Shield Association; Buchanan Family Foundation;
CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia
Research Association; Fresenius-Biotech North America, Inc.; Gamida Cell
Teva Joint Venture Ltd.; Genentech, Inc.; Genzyme Corporation;
GlaxoSmithKline; Kiadis Pharma; The Leukemia & Lymphoma Society; The
Medical College of Wisconsin; Millennium Pharmaceuticals, Inc.; Milliman
USA, Inc.; Miltenvi Biotec, Inc.; National Marrow Donor Program; Optum
Healthcare Solutions, Inc.; Otsuka America Pharmaceutical, Inc.; Seattle
Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; Swedish Orphan
Biovitrum; THERAKOS, Inc.; and Wellpoint, Inc. The views expressed in
this article do not reflect the official policy or position of the
National Institute of Health, the Department of the Navy, the Department
of Defense, or any other agency of the U.S. Government.
NR 30
TC 1
Z9 2
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD SEP
PY 2012
VL 18
IS 9
BP 1401
EP 1406
DI 10.1016/j.bbmt.2012.02.007
PG 6
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 996VF
UT WOS:000308122200012
PM 22387349
ER
PT J
AU Ballen, KK
Woolfrey, AE
Zhu, XC
Ahn, KW
Wirk, B
Arora, M
George, B
Savani, BN
Bolwell, B
Porter, DL
Copelan, E
Hale, G
Schouten, HC
Lewis, I
Cahn, JY
Halter, J
Cortes, J
Kalaycio, ME
Antin, J
Aljurf, MD
Carabasi, MH
Hamadani, M
McCarthy, P
Pavletic, S
Gupta, V
Deeg, HJ
Maziarz, RT
Horowitz, MM
Saber, W
AF Ballen, Karen K.
Woolfrey, Ann E.
Zhu, Xiaochun
Ahn, Kwang Woo
Wirk, Baldeep
Arora, Mukta
George, Biju
Savani, Bipin N.
Bolwell, Brian
Porter, David L.
Copelan, Ed
Hale, Gregory
Schouten, Harry C.
Lewis, Ian
Cahn, Jean Yves
Halter, Joerg
Cortes, Jorge
Kalaycio, Matt E.
Antin, Joseph
Aljurf, Mahmoud D.
Carabasi, Matthew H.
Hamadani, Mehdi
McCarthy, Philip
Pavletic, Steven
Gupta, Vikas
Deeg, H. Joachim
Maziarz, Richard T.
Horowitz, Mary M.
Saber, Wael
TI Allogeneic Hematopoietic Cell Transplantation for Advanced Polycythemia
Vera and Essential Thrombocythemia
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Transplantation; PV; ET
ID ACUTE MYELOID-LEUKEMIA; MYELODYSPLASTIC SYNDROMES; PRIMARY
MYELOFIBROSIS; CURATIVE THERAPY; RISK-FACTORS; FOLLOW-UP; HYDROXYUREA;
MUTATION; JAK2; CRITERIA
AB Allogeneic hematopoietic cell transplantation (HCT) is curative for selected patients with advanced essential thrombocythemia (ET) or polycythemia vera (PV). From 1990 to 2007, 75 patients with ET (median age 49 years) and 42 patients with PV (median age 53 years) underwent transplantations at the Fred Hutchinson Cancer Research Center (FHCRC; n = 43) or at other Center for International Blood and Marrow Transplant Research (CIBMTR) centers (n = 74). Thirty-eight percent of the patients had splenomegaly and 28% had a prior splen ectomy. Most patients (69% for ET and 67% for PV) received a myeloablative (MA) conditioning regimen. Cumulative incidence of neutrophil engraftment at 28 days was 88% for ET patients and 90% for PV patients. Acute graft-versus-host disease (aGVHD) grades II to IV occurred in 57% and 50% of ET and PV patients, respectively. The 1-year treatment-related mortality (TRM) was 27% for ET and 22% for PV. The 5-year cumulative incidence of relapse was 13% for ET and 30% for PV. Five-year survival/progression-free survival (PFS) was 55%/47% and 71%/48% for ETand PV, respectively. Patients without splenomegaly had faster neutrophil and platelet engraftment, but there were no differences in TRM, survival, or PFS. Presence of myelofibrosis (MF) did not affect engraftment or TRM. Over 45% of the patients who undergo transplantations for ET and PV experience long-term PFS. Biol Blood Marrow Tramp/ant 18: 1446-1454 (2012) (C) 2012 American Society for Blood and Marrow Transplantation
C1 [Ballen, Karen K.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02214 USA.
[Woolfrey, Ann E.; Deeg, H. Joachim] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Zhu, Xiaochun; Horowitz, Mary M.; Saber, Wael] Med Coll Wisconsin, Dept Med, CIBMTR, Milwaukee, WI 53226 USA.
[Ahn, Kwang Woo] Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA.
[Wirk, Baldeep] Univ Florida, Shands Healthcare, Dept Hematol Oncol, Gainesville, FL USA.
[Arora, Mukta] Univ Minnesota, Med Ctr, Dept Hematol Oncol & Transplant, Minneapolis, MN 55455 USA.
[George, Biju] Christian Med Coll & Hosp, Dept Hematol, Vellore 632004, Tamil Nadu, India.
[Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Brentwood, TN USA.
[Bolwell, Brian; Copelan, Ed; Kalaycio, Matt E.] Cleveland Clin, Dept Bone Marrow Transplant, Cleveland, OH 44106 USA.
[Porter, David L.] Univ Penn, Med Ctr, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Hale, Gregory] Univ S Florida, All Childrens Hosp, Dept Pediat Hematol Oncol BMT, St Petersburg, FL 33701 USA.
[Schouten, Harry C.] Acad Ziekenhuis, Maastricht, Netherlands.
[Lewis, Ian] Royal Adelaide Hosp, S Australia Pathol, Haematol & Bone Marrow Transplant Unit, Adelaide, SA 5000, Australia.
[Cahn, Jean Yves] CHU Grenoble, Hop A Michallon, Dept Hematol, F-38043 Grenoble, France.
[Halter, Joerg] Univ Basel Hosp, Dept Internal Med, CH-4031 Basel, Switzerland.
[Cortes, Jorge] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Antin, Joseph] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Aljurf, Mahmoud D.] King Faisal Specialist Hosp & Res Ctr, Dept Oncol, Riyadh 11211, Saudi Arabia.
[Carabasi, Matthew H.] Thomas Jefferson Univ Hosp, Dept Med Oncol, Philadelphia, PA 19107 USA.
[Hamadani, Mehdi] W Virginia Univ Hosp Inc, Dept Hematol Oncol, Morgantown, WV USA.
[McCarthy, Philip] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA.
[Pavletic, Steven] NCI, Graft Vs Host & Autoimmun Unit, NIH, Bethesda, MD 20892 USA.
[Gupta, Vikas] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada.
[Maziarz, Richard T.] Oregon Hlth & Sci Univ, Ctr Hematol Malignancies, Portland, OR 97201 USA.
RP Ballen, KK (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, 0 Emerson,Suite 118, Boston, MA 02214 USA.
EM kballen@partners.org
RI Cahn, Jean-Yves/M-6493-2014;
OI Hamadani, Mehdi/0000-0001-5372-510X
FU Public Health Service Grant/Cooperative Agreement from the National
Cancer Institute (NCI) [U24-CA76518]; National Heart, Lung, and Blood
Institute (NIMBI); National Institute of Allergy and Infectious Diseases
(NRID); NIMBI [5U01HL069294]; NCI; Health Resources and Services
Administration (HRSA/DHHS) [HHSH234200637015C]; Office of Naval Research
[N00014-06-1-0704, N00014-08-1-0058]; Allos, Inc.; Amgen, Inc.;
Angioblast
FX The CIBMTR is supported by Public Health Service Grant/Cooperative
Agreement U24-CA76518 from the National Cancer Institute (NCI), the
National Heart, Lung, and Blood Institute (NIMBI), and the National
Institute of Allergy and Infectious Diseases (NRID); a Grant/Cooperative
Agreement 5U01HL069294 from NIMBI and NCI; a contract HHSH234200637015C
with Health Resources and Services Administration (HRSA/DHHS); two
Grants N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval
Research; and grants from Allos, Inc.; Amgen, Inc.; Angioblast;
anonymous donation to the Medical College of Wisconsin; Ariad; Be the
Match Foundation; Blue Cross and Blue Shield Association; Buchanan
Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH;
Children's Leukemia Research Association; Fresenius-Biotech North
America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.;
Genzyme Corporation; GlaxSmithKline; Kiadis Pharma; The Leukemia &
Lymphoma Society; The Medical College of Wisconsin; Millennium
Pharmaceuticals, Inc.; Milliman USA, Inc.; Miltenyi Biotec, Inc.;
National Marrow Donor Program; Optum Healthcare Solutions, Inc.; Osiris
Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; RemedyMD;
Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; Swedish
Orphan Biovitrum; Tarix Pharmaceuticals; Teva Neuroscience, Inc.;
THERAKOS, Inc.; and Wellpoint, Inc. The views expressed in this article
do not reflect the official policy or position of the National Institute
of Health, the Department of the Navy, the Department of Defense, or any
other agency of the U.S. Government.
NR 35
TC 7
Z9 7
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD SEP
PY 2012
VL 18
IS 9
BP 1446
EP 1454
DI 10.1016/j.bbmt.2012.03.009
PG 9
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 996VF
UT WOS:000308122200018
PM 22449610
ER
PT J
AU Vandeleur, C
Rothen, S
Gholam-Rezaee, M
Castelao, E
Vidal, S
Favre, S
Ferrero, F
Halfon, O
Fumeaux, P
Merikangas, KR
Aubry, JM
Burstein, M
Preisig, M
AF Vandeleur, Caroline
Rothen, Stephane
Gholam-Rezaee, Mehdi
Castelao, Enrique
Vidal, Sonia
Favre, Sophie
Ferrero, Francois
Halfon, Olivier
Fumeaux, Pierre
Merikangas, Kathleen R.
Aubry, Jean-Michel
Burstein, Marcy
Preisig, Martin
TI Mental disorders in offspring of parents with bipolar and major
depressive disorders
SO BIPOLAR DISORDERS
LA English
DT Article
DE bipolar disorder; co-parents; DSM-IV mental disorders in offspring;
high-risk offspring; major depressive disorder
ID FAMILY-HISTORY METHOD; TEST-RETEST RELIABILITY; INTER-INFORMANT
AGREEMENT; GENETIC-STUDIES DIGS; DIAGNOSTIC INTERVIEW;
PSYCHIATRIC-DISORDERS; HIGH-RISK; ANXIETY DISORDERS; PSYCHOPATHOLOGY;
CHILDREN
AB Vandeleur C, Rothen S, Gholam-Rezaee M, Castelao E, Vidal S, Favre S, Ferrero F, Halfon O, Fumeaux P, Merikangas KR, Aubry J-M, Burstein M, Preisig M. Mental disorders in offspring of parents with bipolar and major depressive disorders. Bipolar Disord 2012: 14: 641653. (c) 2012 The Authors. Journal compilation (c) 2012 John Wiley & Sons A/S. Objectives: There is limited information on the specificity of associations between parental bipolar disorder (BPD) and major depressive disorder (MDD) and the risk of psychopathology in offspring. The chief aim of the present study was to investigate the association between mood disorder subtypes in the two parents and mental disorders in the offspring. Methods: A total of 376 offspring (aged 6.017.9 years; mean = 11.5 years) of 72 patients with BPD (139 offspring), 56 patients with MDD (110 offspring), and 66 controls (127 offspring) participated in a family study conducted in two university hospital centers in Switzerland. Probands, offspring, and biological co-parents were interviewed by psychologists blind to proband diagnoses, using a semi-structured diagnostic interview. Results: Rates of mood and anxiety disorders were elevated among offspring of BPD probands (34.5% any mood; 42.5% any anxiety) and MDD probands (25.5% any mood; 44.6% any anxiety) as compared to those of controls (12.6% any mood; 22.8% any anxiety). Moreover, recurrent MDD was more frequent among offspring of BPD probands (7.9%) than those of controls (1.6%). Parental concordance for bipolar spectrum disorders was associated with a further elevation in the rates of mood disorders in offspring (64.3% both parents versus 27.2% one parent). Conclusions: These findings provide unique information on the broad manifestations of parental mood disorders in their offspring. The earlier onset and increased risk of recurrent MDD in the offspring of parents with BPD compared to those of controls suggests that the episodicity characterizing BPD may emerge in childhood and adolescence.
C1 [Vandeleur, Caroline; Rothen, Stephane; Vidal, Sonia; Favre, Sophie; Ferrero, Francois; Aubry, Jean-Michel] Univ Hosp Geneva, Dept Mental Hlth & Psychiat, Lausanne, Switzerland.
[Vandeleur, Caroline; Rothen, Stephane; Gholam-Rezaee, Mehdi; Castelao, Enrique; Vidal, Sonia; Halfon, Olivier; Fumeaux, Pierre; Preisig, Martin] Univ Lausanne Hosp, Dept Psychiat, Lausanne, Switzerland.
[Merikangas, Kathleen R.; Burstein, Marcy] NIMH, Genet Epidemiol Res Branch, Intramural Res Program, Bethesda, MD 20892 USA.
RP Vandeleur, C (reprint author), Univ Lausanne Hosp, Dept Psychiat, Site Cery, CH-1008 Prilly, Switzerland.
EM caroline.vandeleur@chuv.ch
RI Rothen, Stephane/E-8325-2014; Preisig, Martin/H-3441-2016;
OI Rothen, Stephane/0000-0003-3891-277X; Castelao,
Enrique/0000-0003-1966-3683
FU Swiss National Foundation (SNF) [3200-040677, 32003B-105969,
32003B-118326, 3200-049746, 3200-061974]; GlaxoSmithKline Clinical
Genetics
FX This research was supported by five grants from the Swiss National
Foundation (SNF: #3200-040677, #32003B-105969, and #32003B-118326 to FF;
and #3200-049746 and #3200-061974 to MP), and a grant from
GlaxoSmithKline Clinical Genetics. The funders had no involvement in any
aspect of this study.
NR 42
TC 25
Z9 26
U1 1
U2 16
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD SEP
PY 2012
VL 14
IS 6
BP 641
EP 653
DI 10.1111/j.1399-5618.2012.01048.x
PG 13
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 999CN
UT WOS:000308286800007
PM 22938168
ER
PT J
AU Ngoma, T
Adde, M
Durosinmi, M
Githang'a, J
Aken'Ova, Y
Kaijage, J
Adeodou, O
Rajab, J
Brown, BJ
Leoncini, L
Naresh, K
Raphael, M
Hurwitz, N
Scanlan, P
Rohatiner, A
Venzon, D
Magrath, I
AF Ngoma, Twalib
Adde, Melissa
Durosinmi, Muheez
Githang'a, Jessie
Aken'Ova, Yetunde
Kaijage, Jane
Adeodou, Oluwagbemiga
Rajab, Jamilla
Brown, Biobele J.
Leoncini, Lorenzo
Naresh, Kikkeri
Raphael, Martine
Hurwitz, Nina
Scanlan, Patricia
Rohatiner, Ama
Venzon, David
Magrath, Ian
TI Treatment of Burkitt lymphoma in equatorial Africa using a simple
three-drug combination followed by a salvage regimen for patients with
persistent or recurrent disease
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE childhood haematological malignancies; clinical research; chemotherapy
ID LONG-TERM SURVIVAL; SUB-SAHARAN AFRICA; B-CELL LYMPHOMAS;
CYCLOPHOSPHAMIDE MONOTHERAPY; TUMOR BURDEN; CHEMOTHERAPY; CHILDREN;
PROTOCOL; ADULTS; EXPERIENCE
AB Prior to the introduction of the International Network for Cancer Treatment and Research (INCTR) protocol INCTR 03-06, survival of patients with Burkitt lymphoma at four tertiary care centres in equatorial Africa was probably no more than 1020%. The results reported here for 356 patients have demonstrated marked improvement in survival through the use of a uniform treatment protocol consisting of cyclophosphamide, methotrexate, vincristine, and intrathecal therapy, and the introduction of non-cross resistant second-line (salvage) therapy, consisting of ifosfamide, mesna, etoposide and cytarabine, when patients failed to achieve a complete response to first-line therapy or relapsed early. Overall survival rates of 67% and 62% were observed at 1 and 2 years (relapse is rare after 1 year of remission). Of interest was the small impact of cerebrospinal fluid (CSF) and bone marrow involvement on outcome. However, the presence or absence of abdominal involvement clearly defined two prognostic groups. An additional finding was the association between CSF pleocytosis and orbital tumours, suggesting that spread of tumour cells to the central nervous system may sometimes occur via direct involvement of cranial nerves in the orbit. Survival rates may be increased in patients with abdominal involvement by combining first- and second-line therapy, but verification will require a further clinical study.
C1 [Adde, Melissa; Hurwitz, Nina; Scanlan, Patricia; Rohatiner, Ama; Magrath, Ian] Int Network Canc Treatment & Res, B-1180 Brussels, Belgium.
[Ngoma, Twalib; Kaijage, Jane] Ocean Rd Canc Inst, Dar Es Salaam, Tanzania.
[Durosinmi, Muheez; Adeodou, Oluwagbemiga] Obafemi Awolowo Univ Teaching Hosp Complex, Ife, Nigeria.
[Githang'a, Jessie; Rajab, Jamilla] Kenyatta Natl Hosp, Nairobi, Kenya.
[Aken'Ova, Yetunde; Brown, Biobele J.] Univ Coll Ibadan Hosp, Ibadan, Nigeria.
[Leoncini, Lorenzo] Univ Siena, I-53100 Siena, Italy.
[Naresh, Kikkeri] Univ London Imperial Coll Sci Technol & Med, London, England.
[Raphael, Martine] Bicetre Univ Paris, Hop Univ Paris S, Paris, France.
[Hurwitz, Nina] Univ Basel, Basel, Switzerland.
[Venzon, David] NCI, Bethesda, MD 20892 USA.
[Magrath, Ian] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
RP Magrath, I (reprint author), Int Network Canc Treatment & Res, Rue Engeland 642, B-1180 Brussels, Belgium.
EM imagrath@inctr.be
OI Brown, Biobele/0000-0001-6981-9872
FU Office of HIV/AIDs Malignancy of the National Cancer Institute (NCI),
National Institutes of Health (NIH), USA; Office of International
Affairs, NCI, NIH, USA; INCTR UK Challenge Fund; Georgetown University
Hospital, Washington, DC, USA
FX This work was partly supported by a task order from the Office of
HIV/AIDs Malignancy of the National Cancer Institute (NCI), National
Institutes of Health (NIH), USA and from core funding provided via the
Office of International Affairs, NCI, NIH, USA. Cytocentrifuges and
training in the use of these machines was supported by MundiPharma
International Ltd., Cambridge, UK. The INCTR UK Challenge Fund provided
financial support for the purchase of chemotherapy and antibiotics
through donations made to the Christopher Niblett Memorial Fund.
Georgetown University Hospital, Washington, DC, USA provided financial
support for the purchase of chemotherapy and antibiotics through
donations made by families and friends of paediatric cancer patients
treated at the Lombardi Cancer Center. INCTR would like to acknowledge
the data managers at the participating institutions for their
contributions to the study: Seif Mkamba (OCRI), Devotha Kovaga (ORCI),
Lukman Bashir (OAUTHC), Oliver Oruko (KNH), and Tosin Oladejo (UCH), and
it would also like to acknowledge former data managers of INCTR's
Clinical Trials Office staff, Lolita Lantican and Carol Falcon. Our
thanks are due to all hospital and laboratory staff that participated in
the care of these patients. Principal investigators, who were involved
in the design and conduct of the study included Twalib Ngoma, Muheez
Durosinmi, Jessie Githanga and Yetunde Aken'Ova. Other medical staff who
played a major role in patient care included Jane Kaijage, Biobele
Brown, Patricia Scanlan, Oluwagbemiga Adeodou and Jamilla Rajab. INCTR
Pathologists who reviewed the diagnostic samples and provided training
for African pathologists included Lorenzo Leoncini, Kikkeri Naresh,
Martine Raphael and Nina Hurwitz. The study was coordinated by Melissa
Adde, who wrote the protocol document, organized scientific and ethical
review, provided annual reports to the INCTR ethical review committee,
ensured that all participating enters undertook ethical review,
performed monitoring visits as well as training of the data managers.
Melissa Adde also provided queries in response to unclear entries in the
CRFs, supervised all aspects of data collection, training of the data
managers (continuing throughout the study) and played a major role in
the analysis of the data and the writing of the manuscript. Ama
Rohatiner assisted in training of PIs, development of the protocol and
monitoring. Ian Magrath had a major role in the design of the protocol,
provided advice and consultation on specific cases, and had a major role
in the analysis of the data and the writing of the manuscript. David
Venzon was the study statistician and was involved in the writing of the
statistical section of the protocol, the analysis of the data, including
choice and performance of statistical methods, and participated in the
writing of the manuscript.
NR 42
TC 13
Z9 13
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1048
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD SEP
PY 2012
VL 158
IS 6
BP 749
EP 762
DI 10.1111/j.1365-2141.2012.09236.x
PG 14
WC Hematology
SC Hematology
GA 995TU
UT WOS:000308036600009
PM 22844968
ER
PT J
AU Blink, M
van den Heuvel-Eibrink, MM
Aalbers, AM
Balgobind, BV
Hollink, IHIM
Meijerink, JPP
van der Velden, VHJ
Beverloo, BH
de Haas, V
Hasle, H
Reinhardt, D
Klusmann, JH
Pieters, R
Calado, RT
Zwaan, CM
AF Blink, Marjolein
van den Heuvel-Eibrink, Marry M.
Aalbers, Anna M.
Balgobind, Brian V.
Hollink, Iris H. I. M.
Meijerink, Jules P. P.
van der Velden, Vincent H. J.
Beverloo, Berna H.
de Haas, Valerie
Hasle, Henrik
Reinhardt, Dirk
Klusmann, Jan-Henning
Pieters, Rob
Calado, Rodrigo T.
Zwaan, Christian M.
TI High frequency of copy number alterations in myeloid leukaemia of Down
syndrome
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Letter
DE acute leukaemia; Down syndrome; copy number alterations
ID CHILDREN
C1 [Blink, Marjolein; van den Heuvel-Eibrink, Marry M.; Aalbers, Anna M.; Balgobind, Brian V.; Hollink, Iris H. I. M.; Meijerink, Jules P. P.; Pieters, Rob; Zwaan, Christian M.] Erasmus MC Sophia Childrens Hosp, Dept Paediat Oncol Haematol, Rotterdam, Netherlands.
[Aalbers, Anna M.; Calado, Rodrigo T.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Aalbers, Anna M.; van der Velden, Vincent H. J.] Univ Med Ctr, Erasmus MC, Dept Immunol, Rotterdam, Netherlands.
[Beverloo, Berna H.] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands.
[de Haas, Valerie] Dutch Childhood Oncol Grp, The Hague, Netherlands.
[Hasle, Henrik] Aarhus Univ, Hosp Skejby, Nord Soc Paediat Haematol & Oncol NOPHO, Dept Paediat, Aarhus, Denmark.
[Reinhardt, Dirk; Klusmann, Jan-Henning] Hannover Med Sch, Dept Paediat Oncol Haematol, AML BFM Study Grp, D-3000 Hannover, Germany.
RP Blink, M (reprint author), Erasmus MC Sophia Childrens Hosp, Dept Paediat Oncol Haematol, Rotterdam, Netherlands.
EM c.m.zwaan@erasmusmc.nl
RI Calado, Rodrigo/G-2619-2011; Reinhardt, Dirk/D-3939-2011; Klusmann,
Jan-Henning/M-9655-2015; Meijerink, Jules/D-4393-2017;
OI Reinhardt, Dirk/0000-0003-4313-9056; Klusmann,
Jan-Henning/0000-0002-1070-0727; Meijerink, Jules/0000-0002-6860-798X;
Hasle, Henrik/0000-0003-3976-9231
NR 10
TC 5
Z9 5
U1 0
U2 1
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 2012
VL 158
IS 6
BP 800
EP 803
DI 10.1111/j.1365-2141.2012.09224.x
PG 4
WC Hematology
SC Hematology
GA 995TU
UT WOS:000308036600015
PM 22775985
ER
PT J
AU Reiter, KL
Song, PH
Minasian, L
Good, M
Weiner, BJ
McAlearney, AS
AF Reiter, Kristin L.
Song, Paula H.
Minasian, Lori
Good, Marjorie
Weiner, Bryan J.
McAlearney, Ann Scheck
TI A method for analyzing the business case for provider participation in
the National Cancer Institute's Community Clinical Oncology Program and
similar federally funded, provider-based research networks
SO CANCER
LA English
DT Article
DE investments; clinical trials as a topic; community networks; research
support as topic; health services research; financial management;
financial support; organizational decision making; cost-benefit
analysis; cost and cost analysis
ID IMPLEMENTING EVIDENCE; CARE PRACTICE; HEALTH-CARE
AB BACKGROUND: The Community Clinical Oncology Program (CCOP) plays an essential role in the efforts of the National Cancer Institute (NCI) to increase enrollment in clinical trials. Currently, there is little practical guidance in the literature to assist provider organizations in analyzing the return on investment (ROI), or business case, for establishing and operating a provider-based research network (PBRN) such as the CCOP. In this article, the authors present a conceptual model of the business case for PBRN participation, a spreadsheet-based tool and advice for evaluating the business case for provider participation in a CCOP organization. METHODS: A comparative, case-study approach was used to identify key components of the business case for hospitals attempting to support a CCOP research infrastructure. Semistructured interviews were conducted with providers and administrators. Key themes were identified and used to develop the financial analysis tool. RESULTS: Key components of the business case included CCOP start-up costs, direct revenue from the NCI CCOP grant, direct expenses required to maintain the CCOP research infrastructure, and incidental benefits, most notably downstream revenues from CCOP patients. The authors recognized the value of incidental benefits as an important contributor to the business case for CCOP participation; however, currently, this component is not calculated. CONCLUSIONS: The current results indicated that providing a method for documenting the business case for CCOP or other PBRN involvement will contribute to the long-term sustainability and expansion of these programs by improving providers' understanding of the financial implications of participation. Cancer 2012. (c) 2011 American Cancer Society.
C1 [Reiter, Kristin L.; Weiner, Bryan J.] Univ N Carolina, Dept Hlth Policy & Management, Chapel Hill, NC 27599 USA.
[Song, Paula H.; McAlearney, Ann Scheck] Ohio State Univ, Div Hlth Serv Management & Policy, Columbus, OH 43210 USA.
[Minasian, Lori; Good, Marjorie] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Reiter, KL (reprint author), Univ N Carolina, Dept Hlth Policy & Management, 1104H McGavran Greenberg Hall,CB 7411, Chapel Hill, NC 27599 USA.
EM reiter@email.unc.edu
RI McAlearney, Ann/J-3008-2013
OI McAlearney, Ann/0000-0001-9107-5419
FU National Cancer Institute [R01CA124402]
FX The project described was supported by award R01CA124402 from the
National Cancer Institute.
NR 20
TC 2
Z9 2
U1 0
U2 2
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 1
PY 2012
VL 118
IS 17
BP 4253
EP 4261
DI 10.1002/cncr.27375
PG 9
WC Oncology
SC Oncology
GA 993GN
UT WOS:000307845200023
PM 22213241
ER
PT J
AU Ruczinski, I
Jorgensen, TJ
Shugart, YY
Schaad, YB
Kessing, B
Hoffman-Bolton, J
Helzlsouer, KJ
Kao, WHL
Wheless, L
Francis, L
Alani, RM
Strickland, PT
Smith, MW
Alberg, AJ
AF Ruczinski, Ingo
Jorgensen, Timothy J.
Shugart, Yin Yao
Schaad, Yvette Berthier
Kessing, Bailey
Hoffman-Bolton, Judith
Helzlsouer, Kathy J.
Kao, W. H. Linda
Wheless, Lee
Francis, Lesley
Alani, Rhoda M.
Strickland, Paul T.
Smith, Michael W.
Alberg, Anthony J.
TI A Population-based Study of DNA Repair Gene Variants in Relation to
Non-melanoma Skin Cancer as a Marker of a Cancer-prone Phenotype
SO CARCINOGENESIS
LA English
DT Article
ID XERODERMA-PIGMENTOSUM; COCKAYNE-SYNDROME; FANCONI-ANEMIA; RISK;
POLYMORPHISMS; SUSCEPTIBILITY; GLYCOSYLASE; CHEK2; TDG; ASSOCIATION
AB For unknown reasons, non-melanoma skin cancer (NMSC) is associated with increased risk of other malignancies. Focusing solely on DNA repair or DNA repair-related genes, this study tested the hypothesis that DNA repair gene variants contribute to the increased cancer risk associated with a personal history of NMSC. From the parent CLUE II cohort study, established in 1989 in Washington County, MD, the study consisted of a cancer-free control group (n 5 2296) compared with three mutually exclusive groups of cancer cases ascertained through 2007: (i) Other (non-NMSC) cancer only (n 5 2349); (ii) NMSC only (n 5 694) and (iii) NMSC plus other cancer (n 5 577). The frequency of minor alleles in 759 DNA repair gene single nucleotide polymorphisms (SNPs) was compared in these four groups. Comparing those with both NMSC and other cancer versus those with no cancer, 10 SNPs had allelic trend P-values < 0.01. The two top-ranked SNPs were both within the thymine DNA glycosylase gene (TDG). One was a non-synonymous coding SNP (rs2888805) [per allele odds ratio (OR) 1.40, 95% confidence interval (CI) 1.161.70; P-value 5 0.0006] and the other was an intronic SNP in high linkage disequilibrium with rs2888805 (rs4135150). None of the associations had a P-value < 6.6310(5), the threshold for statistical significance after correcting for multiple comparisons. The results pinpoint DNA repair genes most likely to contribute to the NMSC cancer-prone phenotype. A promising lead is genetic variants in TDG, important not only in base excision repair but also in regulating the epigenome and gene expression, which may contribute to the NMSC-associated increase in overall cancer risk.
C1 [Wheless, Lee; Francis, Lesley; Alberg, Anthony J.] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA.
[Wheless, Lee; Francis, Lesley; Alberg, Anthony J.] Med Univ S Carolina, Div Epidemiol & Biostat, Dept Med, Charleston, SC 29425 USA.
[Ruczinski, Ingo] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Jorgensen, Timothy J.] Georgetown Univ, Sch Med, Dept Radiat Med, Washington, DC USA.
[Shugart, Yin Yao] NIMH, Div Intramural Res Program, Bethesda, MD 20892 USA.
[Schaad, Yvette Berthier; Hoffman-Bolton, Judith; Kao, W. H. Linda; Strickland, Paul T.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Schaad, Yvette Berthier; Kessing, Bailey] NCI, Lab Genom Divers, SAIC Frederick, Frederick, MD 21701 USA.
[Hoffman-Bolton, Judith] George W Comstock Ctr Publ Hlth Res & Prevent, Washington Cty, MD USA.
[Helzlsouer, Kathy J.] Mercy Med Ctr, Baltimore, MD USA.
[Alani, Rhoda M.] Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA.
[Strickland, Paul T.] Johns Hopkins Univ, Dept Environm Hlth Sci, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Smith, Michael W.] NCI, Genet & Genom Grp, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
RP Alberg, AJ (reprint author), Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA.
EM alberg@musc.edu
OI Alani, Rhoda/0000-0003-2741-2665
FU National Cancer Institute (NCI) [R01 CA105069, HHSN26120080001E];
Intramural Research Program of the NCI, Center for Cancer Research;
State of Maryland; Maryland Cigarette Restitution Fund; National Program
of Cancer Registries of the CDC
FX National Cancer Institute (NCI) (R01 CA105069, HHSN26120080001E);
Intramural Research Program of the NCI, Center for Cancer Research.;
Cancer incidence data were provided by the Maryland Cancer Registry,
Center for Cancer Surveillance and Control, Department of Health and
Mental Hygiene, which is funded by the State of Maryland, the Maryland
Cigarette Restitution Fund and the National Program of Cancer Registries
of the CDC to make the cancer registry data available. This publication
does not necessarily reflect the views or policies of the NCI, NIMH,
NIH, US DHHS, the US government or the Maryland Cancer Registry, nor
does mention of trade names, commercial products or organizations imply
endorsement by the US government.
NR 44
TC 12
Z9 14
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
J9 CARCINOGENESIS
JI Carcinogenesis
PD SEP
PY 2012
VL 33
IS 9
BP 1692
EP 1698
DI 10.1093/carcin/bgs170
PG 7
WC Oncology
SC Oncology
GA 995KT
UT WOS:000308007600009
PM 22581838
ER
PT J
AU Yanagida, J
Hammiller, B
Al-Matouq, J
Behrens, M
Trempus, CS
Repertinger, SK
Hansen, LA
AF Yanagida, Jodi
Hammiller, Brianna
Al-Matouq, Jenan
Behrens, Michaela
Trempus, Carol S.
Repertinger, Susan K.
Hansen, Laura A.
TI Accelerated elimination of ultraviolet-induced DNA damage through
apoptosis in CDC25A-deficient skin
SO CARCINOGENESIS
LA English
DT Article
ID MOUSE SKIN; PROTEIN PHOSPHATASE; GENE MUTATION; IN-VIVO; CELLS; CDC25A;
TUMORIGENESIS; CANCER; PHOTOCARCINOGENESIS; CARCINOGENESIS
AB Cell division cycle 25A (CDC25A) is a dual-specificity phosphatase that removes inhibitory phosphates from cyclin-dependent kinases, allowing cell-cycle progression. Activation of cell-cycle checkpoints following DNA damage results in the degradation of CDC25A, leading to cell-cycle arrest. Ultraviolet (UV) irradiation, which causes most skin cancer, results in both DNA damage and CDC25A degradation. We hypothesized that ablation of CDC25A in the skin would increase cell-cycle arrest following UV irradiation, allowing for improved repair of DNA damage and decreased tumorigenesis. Cdc25a fl/ fl/ Krt14-Cre recombinase mice, with decreased CDC25A in the epithelium of the skin, were generated and exposed to UV. UV-induced DNA damage, in the form of cyclopyrimidine dimers and 8-oxo-deoxyguanosine adducts, was eliminated earlier from CDC25A-deficient epidermis. Surprisingly, loss of CDC25A did not alter epidermal proliferation or cell cycle after UV exposure. However, the UV-induced apoptotic response was prolonged in CDC25A-deficient skin. Double labeling of cleaved caspase-3 and the DNA damage marker.H2A. X revealed many of the apoptotic cells in UV-exposed Cdc25a mutant skin had high levels of DNA damage. Induction of skin tumors by UV irradiation of Cdc25a mutant and control mice on a skin tumor susceptible to v-rasHa Tg. AC mouse background revealed UV-induced papillomas in Cdc25a mutants were significantly smaller than in controls in the first 6 weeks following UV exposure, although there was no difference in tumor multiplicity or incidence. Thus, deletion of Cdc25a increased apoptosis and accelerated the elimination of DNA damage following UV but did not substantially alter cell-cycle regulation or tumorigenesis.
C1 [Yanagida, Jodi; Hammiller, Brianna; Al-Matouq, Jenan; Behrens, Michaela; Hansen, Laura A.] Creighton Univ, Sch Med, Dept Biomed Sci, Omaha, NE 68178 USA.
[Trempus, Carol S.] Natl Inst Environm Hlth Sci, Lab Resp Biol, Res Triangle Pk, NC 27709 USA.
[Repertinger, Susan K.] Creighton Univ, Sch Med, Dept Pathol, Omaha, NE 68178 USA.
RP Hansen, LA (reprint author), Creighton Univ, Sch Med, Dept Biomed Sci, 2500 Calif Plaza, Omaha, NE 68178 USA.
EM LHansen@creighton.edu
FU National Institutes of Health [1RO1ES015585]; State of Nebraska Cancer
and Smoking-Related Diseases Research Program; Facilities Improvement
Program from the National Center for Research Resources, National
Institutes of Health [1CO6RR17417-01, G20RR024001]
FX National Institutes of Health (1RO1ES015585) and the State of Nebraska
Cancer and Smoking-Related Diseases Research Program. This investigation
was conducted in a facility constructed with support from Research
Facilities Improvement Program (1CO6RR17417-01, G20RR024001) from the
National Center for Research Resources, National Institutes of Health.
This work was conducted in part in the Intramural Research Division of
the National Institutes of Health/National Institute of Environmental
Health Sciences. The content is solely the responsibility of the authors
and does not necessarily represent the official views of the National
Center for Research Resources or the National Institutes of Health.
NR 34
TC 4
Z9 5
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
J9 CARCINOGENESIS
JI Carcinogenesis
PD SEP
PY 2012
VL 33
IS 9
BP 1754
EP 1761
DI 10.1093/carcin/bgs168
PG 8
WC Oncology
SC Oncology
GA 995KT
UT WOS:000308007600016
PM 22764135
ER
PT J
AU Carlson, BA
Yoo, MH
Tobe, R
Mueller, C
Naranjo-Suarez, S
Hoffmann, VJ
Gladyshev, VN
Hatfield, DL
AF Carlson, Bradley A.
Yoo, Min-Hyuk
Tobe, Ryuta
Mueller, Charles
Naranjo-Suarez, Salvador
Hoffmann, Victoria J.
Gladyshev, Vadim N.
Hatfield, Dolph L.
TI Thioredoxin reductase 1 protects against chemically induced
hepatocarcinogenesis via control of cellular redox homeostasis
SO CARCINOGENESIS
LA English
DT Article
ID CANCER-THERAPY; GLUTATHIONE; SELENOPROTEINS; DEFICIENCY; SELENIUM;
CELLS; GENE; THIOREDOXIN-REDUCTASE-1; SELENOCYSTEINE; EMBRYOGENESIS
AB Thioredoxin reductase 1 (TR1) controls the redox state of protein thiols in mammalian cells and has been shown to have roles in both preventing and promoting cancer. To define the role of this selenoenzyme in hepatocellular carcinoma development, we examined tumor incidence in the liver of mice with tissue- specific knockout of mouse TR1 subjected to the liver carcinogen, diethylnitrosamine (DEN). TR1- deficient livers manifested 90% tumor incidence compared with 16% in control livers. The TR1- dependent effect was observed independent of sex, and, in control mice, tumorigenesis did not affect the expression of TR1. On the other hand, we observed upregulation of another selenoenzyme, glutathione peroxidase 2 (GPx2), and components of the glutathione (GSH) system, including those that generate reduced GSH. Overall, this study shows that TR1 protects against chemically induced hepatocarcinogenesis via the control of the cellular redox state, whereas its role in promoting this type of cancer is minimal.
C1 [Carlson, Bradley A.; Yoo, Min-Hyuk; Tobe, Ryuta; Mueller, Charles; Naranjo-Suarez, Salvador; Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Bethesda, MD 20892 USA.
[Hoffmann, Victoria J.] NIH, Off Director, Diagnost & Res Serv Branch, Bethesda, MD 20892 USA.
[Gladyshev, Vadim N.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA.
[Gladyshev, Vadim N.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Hatfield, DL (reprint author), NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Bethesda, MD 20892 USA.
EM hatfield@mail.nih.gov
RI Gladyshev, Vadim/A-9894-2013
FU National Institutes of Health NCI Intramural Research Program; Center
for Cancer Research; National Institutes of Health [GM065204, CA080946]
FX National Institutes of Health NCI Intramural Research Program and the
Center for Cancer Research (to D. L. H.) and National Institutes of
Health Grants GM065204 and CA080946 (to V.N.G.).
NR 41
TC 25
Z9 26
U1 0
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
J9 CARCINOGENESIS
JI Carcinogenesis
PD SEP
PY 2012
VL 33
IS 9
BP 1806
EP 1813
DI 10.1093/carcin/bgs230
PG 8
WC Oncology
SC Oncology
GA 995KT
UT WOS:000308007600022
PM 22791808
ER
PT J
AU Xie, H
Zhu, F
Huang, ZN
Lee, MH
Kim, DJ
Li, X
Lim, DY
Jung, SK
Kang, S
Li, HT
Reddy, K
Wang, L
Ma, WY
Lubet, RA
Bode, AM
Dong, ZG
AF Xie, Hua
Zhu, Feng
Huang, Zunnan
Lee, Mee-Hyun
Kim, Dong Joon
Li, Xiang
Lim, Do Young
Jung, Sung Keun
Kang, Soouk
Li, Haitao
Reddy, Kanamata
Wang, Lei
Ma, Weiya
Lubet, Ronald A.
Bode, Ann M.
Dong, Zigang
TI Identification of mammalian target of rapamycin as a direct target of
fenretinide both in vitro and in vivo
SO CARCINOGENESIS
LA English
DT Article
ID HUMAN LUNG CARCINOMAS; TRANS-RETINOIC ACID; GROWTH-FACTOR; CANCER-CELLS;
ANTITUMOR-ACTIVITY; BREAST-CANCER; MTOR; MECHANISMS; INHIBITION;
APOPTOSIS
AB N-(4-hydroxyphenyl) retinamide (4HPR, fenretinide) is a synthetic retinoid that has been tested in clinical trials as a cancer therapeutic and chemopreventive agent. Although 4HPR has been shown to be cytotoxic to many kinds of cancer cells, the underlying molecular mechanisms are only partially understood. Until now, no direct cancer-related molecular target has been reported to be involved in the antitumor activities of 4HPR. Herein, we found that 4HPR inhibited mammalian target of rapamycin (mTOR) kinase activity by directly binding with mTOR, which suppressed the activities of both the mTORC1 and the mTORC2 complexes. The predicted binding mode of 4HPR with mTOR was based on a homology computer model, which showed that 4HPR could bind in the ATP-binding pocket of the mTOR protein through hydrogen bonds and hydrophobic interactions. In vitro studies also showed that 4HPR attenuated mTOR downstream signaling in a panel of non-small-cell lung cancer cells, resulting in growth inhibition. Moreover, knockdown of mTOR in cancer cells decreased their sensitivity to 4HPR. Results of an in vivo study demonstrated that i.p. injection of 4HPR in A549 lung tumor-bearing mice effectively suppressed cancer growth. The expression of mTOR downstream signaling molecules in tumor tissues was also decreased after 4HPR treatment. Taken together, our results are the first to identify mTOR as a direct antitumor target of 4HPR both in vitro and in vivo, providing a valuable rationale for guiding the clinical uses of 4HPR.
C1 [Xie, Hua; Zhu, Feng; Huang, Zunnan; Lee, Mee-Hyun; Kim, Dong Joon; Li, Xiang; Lim, Do Young; Jung, Sung Keun; Kang, Soouk; Li, Haitao; Reddy, Kanamata; Wang, Lei; Ma, Weiya; Bode, Ann M.; Dong, Zigang] Univ Minnesota, Hormel Inst, Austin, MN 55912 USA.
[Lubet, Ronald A.] NCI, NIH, Bethesda, MD 20892 USA.
RP Dong, ZG (reprint author), Univ Minnesota, Hormel Inst, 801 16th Ave NE, Austin, MN 55912 USA.
EM zgdong@hi.umn.edu
RI ZHU, Feng/G-3567-2010;
OI Kanamata Reddy, Srinivasa Reddy/0000-0003-3733-7531; Huang,
Zunnan/0000-0002-5821-703X
FU Hormel Foundation; National Institutes of Health [CA027502, CA120388,
R37 CA081064, ES016548]; NCI [HHSN-261200533001C-NO1-CN-53301,
N01-CN-43309-18018-01WA 13B]
FX The Hormel Foundation and National Institutes of Health (CA027502,
CA120388, R37 CA081064 and ES016548) and NCI Contract Number
HHSN-261200533001C-NO1-CN-53301 and N01-CN-43309-18018-01WA 13B.
NR 39
TC 11
Z9 11
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
J9 CARCINOGENESIS
JI Carcinogenesis
PD SEP
PY 2012
VL 33
IS 9
BP 1814
EP 1821
DI 10.1093/carcin/bgs234
PG 8
WC Oncology
SC Oncology
GA 995KT
UT WOS:000308007600023
PM 22798378
ER
PT J
AU Uldrick, TS
Polizzotto, MN
Yarchoan, R
AF Uldrick, Thomas S.
Polizzotto, Mark N.
Yarchoan, Robert
TI Recent advances in Kaposi sarcoma herpesvirus-associated multicentric
Castleman disease
SO CURRENT OPINION IN ONCOLOGY
LA English
DT Review
DE human herpesvirus-8; Kaposi sarcoma herpesvirus; KSHV-associated
inflammatory cytokine syndrome; multicentric Castleman disease; viral
interleukin-6
ID PRIMARY EFFUSION LYMPHOMA; NON-HODGKIN-LYMPHOMA; NF-KAPPA-B; ENCODED
VIRAL INTERLEUKIN-6; ENDOTHELIAL GROWTH-FACTOR; VIRUS-INFECTED PATIENTS;
HIV-NEGATIVE PATIENTS; BETA-DEFICIENT MICE; PERIPHERAL-BLOOD;
DNA-SEQUENCES
AB Purpose of review
The discovery of Kaposi sarcoma herpesvirus (KSHV) led to recognition of KSHV-associated multicentric Castleman disease (MCD) as a distinct lymphoproliferative disorder. The pathogenesis of KSHV-MCD is attributed to proliferation of KSHV-infected B cells, production of KSHV-encoded viral interleukin 6 by these cells, and dysregulation of human interleukin 6 and interleukin 10. This article reviews advances in the field of disease pathogenesis and targeted therapies.
Recent findings
Our understanding of the pathogenesis of KSHV-MCD has increased in recent years and improved therapies have been developed. Recent studies demonstrate that the anti-CD20 monoclonal antibody, rituximab, as well as virus-activated cytotoxic therapy using high-dose zidovudine and valganciclovir, can control symptoms and decrease adenopathy. With treatment, 1-year survival now exceeds 85%. Interestingly, even in the absence of pathologic findings of MCD, KSHV-infected patients may have inflammatory symptoms, excess cytokine production, and elevated KSHV viral load similar to KSHV-associated MCD. The term KSHV-associated inflammatory cytokine syndrome has been proposed to describe such patients.
Summary
Recent advances in targeted therapy have improved outcomes in KSHV-MCD, and decreased need for cytotoxic chemotherapy. Improved understanding of the pathogenesis of KSHV-MCD and KSHV-associated inflammatory cytokine syndrome is needed, and will likely lead to additional advances in therapy for these disorders.
C1 [Uldrick, Thomas S.; Polizzotto, Mark N.; Yarchoan, Robert] NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Uldrick, TS (reprint author), 10 Ctr Dr,Room 6N106,MSC 1868, Bethesda, MD 20892 USA.
EM uldrickts@mail.nih.gov
FU Intramural Research Program, National Cancer Institute (NCI), NIH; NCI,
NIH [HHSN261200800001E]
FX This research was supported in part by the Intramural Research Program,
National Cancer Institute (NCI), NIH. Additional funding comes from the
NCI, NIH, under Contract No. HHSN261200800001E.
NR 146
TC 28
Z9 32
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-8746
J9 CURR OPIN ONCOL
JI Curr. Opin. Oncol.
PD SEP
PY 2012
VL 24
IS 5
BP 495
EP 505
DI 10.1097/CCO.0b013e328355e0f3
PG 11
WC Oncology
SC Oncology
GA 991DK
UT WOS:000307681500006
PM 22729151
ER
PT J
AU Goedert, JJ
Bower, M
AF Goedert, James J.
Bower, Mark
TI Impact of highly effective antiretroviral therapy on the risk for
Hodgkin lymphoma among people with human immunodeficiency virus
infection
SO CURRENT OPINION IN ONCOLOGY
LA English
DT Review
DE acquired immunodeficiency syndrome; antiretroviral therapy; cancer
chemotherapy; CD4 count; Hodgkin lymphoma; human immunodeficiency virus
ID EPSTEIN-BARR-VIRUS; SWISS HIV COHORT; UNITED-STATES; CANCER INCIDENCE;
AIDS; DISEASE; POPULATION; PATTERNS
AB Purpose of review
To estimate the impact of highly effective antiretroviral therapy (ART) on the incidence and prognosis of Hodgkin lymphoma among people with human immunodeficiency virus infection or AIDS (PWHA).
Recent findings
Age-adjusted incidence of Hodgkin lymphoma in PWHA is unchanged and is still five-fold to fifteen-fold higher than in the general population. Aging of the PWHA population with ART may account for increasing numbers of Hodgkin lymphoma cases. CD4 cell count has a complex relationship to Hodgkin lymphoma risk in PWHA. Depending on the time of measurement, Hodgkin lymphoma risk is highest with 50-249 CD4 cells/mu l, and falling CD4 count on ART may be a harbinger of Hodgkin lymphoma onset. HIV load appears irrelevant to Hodgkin lymphoma. For obscure reasons, Hodgkin lymphoma risk may be elevated soon after starting ART, but the risk is probably modestly reduced with 6 or more months on ART. For PWHA who develop Hodgkin lymphoma, ART and ABVD chemotherapy can be administered safely, with one recent study demonstrating equivalent outcomes for HIV-positive and HIV-negative Hodgkin lymphoma patients.
Summary
Vigilance for Hodgkin lymphoma is needed for immune-deficient PWHA, including those on ART. ART with opportunistic infection prophylaxis enables the delivery of effective chemotherapy for Hodgkin lymphoma, leading to a good prognosis.
C1 [Goedert, James J.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Bower, Mark] Chelsea & Westminster Hosp, Natl HIV Oncol Ctr, London, England.
RP Goedert, JJ (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7068, Rockville, MD 20852 USA.
EM goedertj@mail.nih.gov
OI Bower, Mark/0000-0002-4077-6351
FU Intramural NIH HHS [ZIA CP010214-01]
NR 23
TC 11
Z9 11
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-8746
J9 CURR OPIN ONCOL
JI Curr. Opin. Oncol.
PD SEP
PY 2012
VL 24
IS 5
BP 531
EP 536
DI 10.1097/CCO.0b013e3283560697
PG 6
WC Oncology
SC Oncology
GA 991DK
UT WOS:000307681500010
PM 22729154
ER
PT J
AU Bhatia, K
Shiels, MS
Berg, A
Engels, EA
AF Bhatia, Kishor
Shiels, Meredith S.
Berg, Alexandra
Engels, Eric A.
TI Sarcomas other than Kaposi sarcoma occurring in immunodeficiency:
interpretations from a systematic literature review
SO CURRENT OPINION IN ONCOLOGY
LA English
DT Review
DE AIDS; cancer; EBV; HIV; HHV-8; organ transplant; sarcoma
ID EPSTEIN-BARR-VIRUS; SMOOTH-MUSCLE TUMORS; RENAL-TRANSPLANT RECIPIENT;
OF-THE-LITERATURE; MALIGNANT FIBROUS HISTIOCYTOMA; HIV-POSITIVE PATIENT;
HEPATIC LEIOMYOMATOUS NEOPLASM; DENDRITIC CELL-SARCOMA; A-CASE-REPORT;
ARTERIOVENOUS-FISTULA
AB Purpose of review
In immunodeficiency, an increased sarcoma risk is confirmed for Kaposi's sarcoma. Whether rates of other sarcoma subtypes are elevated in the setting of immunodeficiency is not known. We therefore reviewed published case reports on HIV and AIDS patients and organ transplant recipients with sarcomas. For comparison, we assessed sarcomas in the U.S. general population using Surveillance Epidemiology End Results (SEER) data.
Recent findings
A total of 176 non-Kaposi sarcoma were identified, 75 in people with HIV and AIDS and 101 in transplant recipients. Leiomyosarcomas (n = 101) were the most frequently reported sarcomas, followed by angiosarcomas (n = 23) and fibrohistiocytic tumors (n = 17). Leiomyosarcomas were reported with two age peaks, in children and young adults. Epstein-Barr virus (EBV) was detected in the tumor cells in 85 and 88% of leiomyosarcomas in HIV-infected people and transplant recipients, respectively. Angiosarcomas and fibrohistiocytic tumors were most frequently reported in men. Among kidney transplant recipients, 20% of sarcomas arose at the site of an arteriovenous fistula. In comparison, leiomyoscarcomas, angiosarcomas, and fibrohistiocytic tumors comprised 16.9, 3.8, and 18.7% of sarcomas in the U.S. general population.
Summary
Leiomyosarcoma and angiosarcoma may occur disproportionately in immunodeficiency. Leiomyosarcomas appear causatively linked to EBV, whereas angiosarcomas might be correlated with an arteriovenous fistula. Additional studies are necessary to understand the contribution of immunodeficiency to the cause of these sarcomas.
C1 [Bhatia, Kishor] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Bhatia, K (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd, Bethesda, MD 20892 USA.
EM bhatiak@mail.nih.gov
FU National Cancer Institute
FX This study was funded by the Intramural Research Program of the National
Cancer Institute.
NR 200
TC 17
Z9 19
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-8746
J9 CURR OPIN ONCOL
JI Curr. Opin. Oncol.
PD SEP
PY 2012
VL 24
IS 5
BP 537
EP 546
DI 10.1097/CCO.0b013e328355e115
PG 10
WC Oncology
SC Oncology
GA 991DK
UT WOS:000307681500011
PM 22729152
ER
PT J
AU Nandy, K
Gudla, PR
Amundsen, R
Meaburn, KJ
Misteli, T
Lockett, SJ
AF Nandy, Kaustav
Gudla, Prabhakar R.
Amundsen, Ryan
Meaburn, Karen J.
Misteli, Tom
Lockett, Stephen J.
TI Automatic segmentation and supervised learning-based selection of nuclei
in cancer tissue images
SO CYTOMETRY PART A
LA English
DT Article
DE tissue segmentation; watershed; artificial neural network; cancer
diagnosis; image analysis; pattern classification
ID CELL-NUCLEI; MICROSCOPE IMAGES; ALGORITHM; CLASSIFICATION; DISTANCE;
BIOLOGY; SYSTEM
AB Analysis of preferential localization of certain genes within the cell nuclei is emerging as a new technique for the diagnosis of breast cancer. Quantitation requires accurate segmentation of 100200 cell nuclei in each tissue section to draw a statistically significant result. Thus, for large-scale analysis, manual processing is too time consuming and subjective. Fortuitously, acquired images generally contain many more nuclei than are needed for analysis. Therefore, we developed an integrated workflow that selects, following automatic segmentation, a subpopulation of accurately delineated nuclei for positioning of fluorescence in situ hybridization-labeled genes of interest. Segmentation was performed by a multistage watershed-based algorithm and screening by an artificial neural network-based pattern recognition engine. The performance of the workflow was quantified in terms of the fraction of automatically selected nuclei that were visually confirmed as well segmented and by the boundary accuracy of the well-segmented nuclei relative to a 2D dynamic programming-based reference segmentation method. Application of the method was demonstrated for discriminating normal and cancerous breast tissue sections based on the differential positioning of the HES5 gene. Automatic results agreed with manual analysis in 11 out of 14 cancers, all four normal cases, and all five noncancerous breast disease cases, thus showing the accuracy and robustness of the proposed approach. (C) Published 2012 Wiley Periodicals, Inc.
C1 [Nandy, Kaustav; Gudla, Prabhakar R.; Lockett, Stephen J.] SAIC Frederick Inc, Opt Microscopy & Anal Lab, Frederick Natl Lab Canc Res, Adv Technol Program, Frederick, MD 21702 USA.
[Amundsen, Ryan] Johns Hopkins Univ, Appl Phys Lab, Dept Assymetr Operat, Laurel, MD 20723 USA.
[Meaburn, Karen J.; Misteli, Tom] NCI, Cell Biol Genomes Grp, NIH, Bethesda, MD 20892 USA.
RP Nandy, K (reprint author), SAIC Frederick Inc, Opt Microscopy & Anal Lab, Frederick Natl Lab Canc Res, Adv Technol Program, POB B, Frederick, MD 21702 USA.
EM nandyk@mail.nih.gov
OI Meaburn, Karen/0000-0002-1327-5957
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; National Institutes of Health, National Cancer
Institute, Center for Cancer Research; Department of Defense Breast
Cancer Idea Award
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 U.S. Government.;
This research was supported in part by the Intramural Research Program
of the National Institutes of Health, National Cancer Institute, Center
for Cancer Research and by a Department of Defense Breast Cancer Idea
Award to Tom Misteli.
NR 58
TC 15
Z9 15
U1 0
U2 21
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 2012
VL 81A
IS 9
BP 743
EP 754
DI 10.1002/cyto.a.22097
PG 12
WC Biochemical Research Methods; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 993EY
UT WOS:000307839900005
PM 22899462
ER
PT J
AU Muniyappa, R
Sowers, JR
AF Muniyappa, Ranganath
Sowers, James R.
TI Endothelial Insulin and IGF-1 Receptors: When Yes Means No
SO DIABETES
LA English
DT Editorial Material
ID FACTOR-I RECEPTOR; GROWTH-FACTOR RECEPTOR; HYBRID RECEPTORS;
NITRIC-OXIDE; SENSITIVITY; CELLS; ADIPOCYTES; RESISTANCE; DISEASE
C1 [Muniyappa, Ranganath] NIDDKD, Clin Endocrine Sect, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
[Sowers, James R.] Univ Missouri, Sch Med, Dept Internal Med, Columbia, MO USA.
[Sowers, James R.] Univ Missouri, Dept Med Pharmacol & Physiol, Sch Med, Columbia, MO USA.
[Sowers, James R.] Harry S Truman Mem Vet Hosp, Columbia, MO 65201 USA.
RP Muniyappa, R (reprint author), NIDDKD, Clin Endocrine Sect, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
EM muniyapr@mail.nih.gov
FU NHLBI NIH HHS [R01 HL107910, R01 HL107910-03, R01 HL073101, R01
HL73101-08]
NR 20
TC 8
Z9 8
U1 0
U2 1
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD SEP
PY 2012
VL 61
IS 9
BP 2225
EP 2227
DI 10.2337/db12-0654
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 998PY
UT WOS:000308254100007
PM 22923650
ER
PT J
AU Long, SA
Rieck, M
Sanda, S
Bollyky, JB
Samuels, PL
Goland, R
Ahmann, A
Rabinovitch, A
Aggarwal, S
Phippard, D
Turka, LA
Ehlers, MR
Bianchine, PJ
Boyle, KD
Adah, SA
Bluestone, JA
Buckner, JH
Greenbaum, CJ
AF Long, S. Alice
Rieck, Mary
Sanda, Srinath
Bollyky, Jennifer B.
Samuels, Peter L.
Goland, Robin
Ahmann, Andrew
Rabinovitch, Alex
Aggarwal, Sudeepta
Phippard, Deborah
Turka, Laurence A.
Ehlers, Mario R.
Bianchine, Peter J.
Boyle, Karen D.
Adah, Steven A.
Bluestone, Jeffrey A.
Buckner, Jane H.
Greenbaum, Carla J.
CA Diabet TrialNet & Immune Tolerance
TI Rapamycin/IL-2 Combination Therapy in Patients With Type 1 Diabetes
Augments Tregs Yet Transiently Impairs beta-cell Function
SO DIABETES
LA English
DT Article
ID REGULATORY T-CELLS; HUMAN AUTOIMMUNE-DISEASES; PLACEBO-CONTROLLED TRIAL;
LOW-DOSE INTERLEUKIN-2; NATURAL-KILLER-CELLS; MULTIPLE-SCLEROSIS;
PERIPHERAL-BLOOD; MAMMALIAN TARGET; DOUBLE-BLIND; NOD MICE
AB Rapamycin/interleukin-2 (IL-2) combination treatment of NOD mice effectively treats autoimmune diabetes. We performed a phase 1 clinical trial to test the safety and immunologic effects of rapamycin/IL-2 combination therapy in type 1 diabetic (T1D) patients. Nine T1D subjects were treated with 2-4 mg/day rapamycin orally for 3 months and 4.5 x 10(6) IU IL-2 s.c. three times per week for 1 month. beta-Cell function was monitored by measuring C-peptide. Immunologic changes were monitored using flow cytometry and serum analyses. Regulatory T cells (Tregs) increased within the first month of therapy, yet clinical and metabolic data demonstrated a transient worsening in all subjects. The increase in Tregs was transient, paralleling IL-2 treatment, whereas the response of Tregs to IL-2, as measured by STAT5 phosphorylation, increased and persisted after treatment. No differences were observed in effector T-cell subset frequencies, but an increase in natural killer cells and eosinophils occurred with IL-2 therapy. Rapainycin/IL-2 therapy, as given in this phase 1 study, resulted in transient beta-cell dysfunction despite an increase in Tregs. Such results highlight the difficulties in translating therapies to the clinic and emphasize the importance of broadly interrogating the immune system to evaluate the effects of therapy. Diabetes 61:2340-2348, 2012
C1 [Sanda, Srinath; Bollyky, Jennifer B.; Greenbaum, Carla J.] Benaroya Res Inst, Diabet Program, Seattle, WA USA.
[Long, S. Alice; Rieck, Mary; Samuels, Peter L.; Buckner, Jane H.] Benaroya Res Inst, Translat Immunol Program, Seattle, WA USA.
[Goland, Robin] Columbia Univ, Med Ctr, Naomi Berrie Diabet Ctr, New York, NY USA.
[Ahmann, Andrew] Oregon Hlth & Sci Univ, Harold Schnitzer Diabet Hlth Ctr, Portland, OR 97201 USA.
[Rabinovitch, Alex] Univ S Dakota, Sioux Falls, SD USA.
[Aggarwal, Sudeepta; Phippard, Deborah; Turka, Laurence A.] Immune Tolerance Network, Tolerance Assays & Data Anal Grp, Bethesda, MD USA.
[Turka, Laurence A.] Harvard Univ, Sch Med, Boston, MA USA.
[Turka, Laurence A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Ehlers, Mario R.] Immune Tolerance Network, Clin Trials Grp, San Francisco, CA USA.
[Bianchine, Peter J.; Adah, Steven A.] NIAID, Div Allergy Immunol & Transplantat, Bethesda, MD 20892 USA.
[Boyle, Karen D.] Rho Fed Syst Div Inc, Chapel Hill, NC USA.
[Bluestone, Jeffrey A.] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA.
[Bluestone, Jeffrey A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
RP Greenbaum, CJ (reprint author), Benaroya Res Inst, Diabet Program, Seattle, WA USA.
EM jbuckner@benaroyaresearch.org; cgreenbaum@benaroyaresearch.org
FU National Institute of Allergy and Infectious Diseases; National
Institute of Diabetes and Digestive and Kidney Diseases; ITN
FX These studies were supported by the National Institute of Allergy and
Infectious Diseases sponsored Immune Tolerance Network (ITN), the
National Institute of Diabetes and Digestive and Kidney Diseases
sponsored Diabetes TrialNet, and an ITN grant to J.H.B.
NR 43
TC 117
Z9 118
U1 1
U2 14
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 2012
VL 61
IS 9
BP 2340
EP 2348
DI 10.2337/db12-0049
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 998PY
UT WOS:000308254100021
PM 22721971
ER
PT J
AU Pan, CQ
Mi, LJ
Bunchorntavakul, C
Karsdon, J
Huang, WM
Singhvi, G
Ghany, MG
Reddy, KR
AF Pan, Calvin Q.
Mi, Li-Jun
Bunchorntavakul, Chalermrat
Karsdon, Jeffrey
Huang, William M.
Singhvi, Gaurav
Ghany, Marc G.
Reddy, K. Rajender
TI Tenofovir Disoproxil Fumarate for Prevention of Vertical Transmission of
Hepatitis B Virus Infection by Highly Viremic Pregnant Women: A Case
Series
SO DIGESTIVE DISEASES AND SCIENCES
LA English
DT Article
DE Hepatitis B virus; Pregnancy; Perinatal transmission; Prevention;
Treatment; Tenofovir
ID BONE-MINERAL DENSITY; PERINATAL TRANSMISSION; NATURAL-HISTORY;
LAMIVUDINE; CHILDREN; TELBIVUDINE; EFFICACY; OUTCOMES; THERAPY; INFANTS
AB Despite appropriate immunoprophylaxis, up to 10 % of infants born to highly viremic hepatitis B virus (HBV-DNA a parts per thousand yen 7 log IU/mL) mothers are infected with HBV. Use of TDF to prevent vertical transmission (VT) by such mothers has not been evaluated.
To evaluate the efficacy and safety of TDF in preventing VT from highly viremic HBV-infected mothers.
Data were collected retrospectively from HBV mono-infected, hepatitis B e antigen (HBeAg) positive, pregnant women between 6/2008 and 11/2010. Cases enrolled were HBV mono-infected mothers who received TDF (300 mg orally once a day) in the third trimester. Those with pregnancy complications or an abnormal fetus on sonography were excluded from use of TDF. All infants received hepatitis B immunoglobulin and vaccination at birth and subsequently.
Eleven Asian mothers received TDF at the median gestational age of 29 (28-32) weeks and the median duration of TDF use before delivery was 10 (7-12) weeks. A significant reduction in serum HBV-DNA was achieved at delivery compared with baseline (mean 5.25 +/- A 1.79 vs. 8.87 +/- A 0.45 log(10) copies/mL, respectively; p < 0.01). Three had serum ALT levels more than 1.5 times the upper limit of normal and two of these normalized before delivery. The 11 infants were born with no obstetric complication or birth defects. Five infants were breastfed. All infants were hepatitis B surface antigen negative 28-36 weeks after birth.
Our preliminary data suggest that TDF use in the third trimester is safe, and effectively prevents VT of HBV from high viremic HBeAg-positive mothers.
C1 [Bunchorntavakul, Chalermrat; Reddy, K. Rajender] Univ Penn, Div Gastroenterol & Hepatol, Dept Med, Philadelphia, PA 19104 USA.
[Pan, Calvin Q.] Mt Sinai Med Ctr, Mt Sinai Sch Med, Dept Med, Div Liver Dis, New York, NY 10029 USA.
[Mi, Li-Jun] New York Downtown Hosp, Dept Internal Med, New York, NY USA.
[Bunchorntavakul, Chalermrat] Rajavithi Hosp, Div Gastroenterol & Hepatol, Dept Med, Minist Publ Hlth, Bangkok, Thailand.
[Karsdon, Jeffrey] New York Downtown Hosp, Div Neonatol, Dept Pediat, New York, NY USA.
[Huang, William M.] New York Downtown Hosp, Div Maternal Fetal Med, Dept Obstet & Gynecol, New York, NY USA.
[Singhvi, Gaurav] Elmhurst Hosp, Div Gastroenterol, Dept Internal Med, Mt Sinai Serv, New York, NY USA.
[Ghany, Marc G.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA.
RP Reddy, KR (reprint author), Univ Penn, Div Gastroenterol & Hepatol, Dept Med, 2 Dulles,3400 Spruce St, Philadelphia, PA 19104 USA.
EM rajender.reddy@uphs.upenn.edu
OI Karsdon, Jeffrey/0000-0002-7060-6134
FU Bristol-Myers Squibb Company; Novartis; Idenix; Roche; Gilead Sciences,
Inc.; Gilead Sciences
FX Calvin Q. Pan received research grants from Bristol-Myers Squibb
Company, Novartis, Idenix, Roche, and Gilead Sciences, Inc. He also
serves as a consultant, advisor, and is on the Speakers Bureau of
Gilead, Bristol Myers Squibb, Novartis, Idenix, Roche, Genentech, Axcan
USA, Schering Plough, Onyx, Three Rivers, Salix, and Pharmasset; Li-Jun
Mi received funding from Gilead Sciences for Investigator-initiated
clinical studies; Chalermrat Bunchorntavakul no conflict of interest;
Jeffrey Karsdon no conflict of interest; William M. Huang paid
consultant for Gilead Sciences, Inc. in the past; Gaurav Singhvi no
conflict of interest; Marc G. Ghany no conflict of interest; K. Rajender
Reddy is an ad hoc advisory board member for Gilead Sciences, Inc.
NR 28
TC 56
Z9 64
U1 2
U2 19
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0163-2116
J9 DIGEST DIS SCI
JI Dig. Dis. Sci.
PD SEP
PY 2012
VL 57
IS 9
BP 2423
EP 2429
DI 10.1007/s10620-012-2187-3
PG 7
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 995VW
UT WOS:000308043300025
PM 22543886
ER
PT J
AU Yang, W
AF Yang, W.
TI DNA lesion recognition and mismatch repair
SO FEBS JOURNAL
LA English
DT Meeting Abstract
CT 22nd IUBMB Congress/37th FEBS Congress
CY SEP 04-09, 2012
CL Seville, SPAIN
SP IUBMB, FEBS
C1 [Yang, W.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 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 1742-464X
J9 FEBS J
JI FEBS J.
PD SEP
PY 2012
VL 279
SU 1
SI SI
BP 6
EP 6
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 996XR
UT WOS:000308128600023
ER
PT J
AU Lee, EK
Kim, W
Gorospe, M
AF Lee, E. K.
Kim, W.
Gorospe, M.
TI Control of glucose homeostasis by RNA-binding protein HuD
SO FEBS JOURNAL
LA English
DT Meeting Abstract
CT 22nd IUBMB Congress/37th FEBS Congress
CY SEP 04-09, 2012
CL Seville, SPAIN
SP IUBMB, FEBS
C1 [Lee, E. K.; Kim, W.; Gorospe, M.] NIA, NIH, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1742-464X
J9 FEBS J
JI FEBS J.
PD SEP
PY 2012
VL 279
SU 1
SI SI
BP 14
EP 14
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 996XR
UT WOS:000308128600048
ER
PT J
AU Gustchina, A
Bhaumik, P
Xiao, H
Horimoto, Y
Yada, RY
Miura, T
Hidaka, K
Kiso, Y
Wlodawer, A
AF Gustchina, A.
Bhaumik, P.
Xiao, H.
Horimoto, Y.
Yada, R. Y.
Miura, T.
Hidaka, K.
Kiso, Y.
Wlodawer, A.
TI Crystallographic investigations of the complexes of plasmepsins with
peptidic inhibitors
SO FEBS JOURNAL
LA English
DT Meeting Abstract
CT 22nd IUBMB Congress/37th FEBS Congress
CY SEP 04-09, 2012
CL Seville, SPAIN
SP IUBMB, FEBS
C1 [Gustchina, A.; Bhaumik, P.; Wlodawer, A.] NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21701 USA.
[Xiao, H.; Horimoto, Y.; Yada, R. Y.] Univ Guelph, Dept Food Sci, Guelph, CA USA.
[Miura, T.] Kyoto Pharmaceut Univ, Dept Med Chem, Yamashina Ku, Kyoto, Japan.
[Miura, T.] Kyoto Pharmaceut Univ, Ctr Frontier Res Med Sci, Yamashina Ku, Kyoto, Japan.
[Hidaka, K.] Kobe Gakuin Univ, Med Chem Lab, Minatojima, Japan.
[Hidaka, K.] Kyoto Pharmaceut Univ, Dept Med Chem, Minatojima, Japan.
[Hidaka, K.] Kyoto Pharmaceut Univ, Ctr Frontier Res Med Sci, Minatojima, Japan.
[Kiso, Y.] Kyoto Pharmaceut Univ, Dept Med Chem, Shiga, Japan.
[Kiso, Y.] Kyoto Pharmaceut Univ, Ctr Frontier Res Med Sci, Shiga, Japan.
[Kiso, Y.] Kobe Gakuin Univ, Med Chem Lab, Shiga, Japan.
[Kiso, Y.] Nagahama Inst Biosci & Technol Nagahama, Lab Peptide Sci, Shiga, Japan.
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 1742-464X
J9 FEBS J
JI FEBS J.
PD SEP
PY 2012
VL 279
SU 1
SI SI
BP 117
EP 117
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 996XR
UT WOS:000308128601209
ER
PT J
AU Cascajo, MV
Siendones, E
Abdelmohsen, K
Willers, IM
Cuezva, JM
Gorospe, M
Navas, P
AF Cascajo, M. V.
Siendones, E.
Abdelmohsen, K.
Willers, I. M.
Cuezva, J. M.
Gorospe, M.
Navas, P.
TI Coenzyme Q biosynthesis is regulated by RNA-protein interaction
SO FEBS JOURNAL
LA English
DT Meeting Abstract
CT 22nd IUBMB Congress/37th FEBS Congress
CY SEP 04-09, 2012
CL Seville, SPAIN
SP IUBMB, FEBS
C1 [Cascajo, M. V.; Siendones, E.; Navas, P.] Univ Pablo de Olavide, CSIC, Ctr Andaluz Biol Desarrollo, Seville, Spain.
[Cascajo, M. V.; Siendones, E.; Navas, P.] ISCIII, CIBERER, Seville, Spain.
[Abdelmohsen, K.; Gorospe, M.] NIA IRP, Lab Mol Biol & Immunol, NIH, Baltimore, MD USA.
[Willers, I. M.; Cuezva, J. M.] Univ Autonoma Madrid, CSIC, Ctr Biol Mol Severo Ochoa, Madrid, Spain.
[Willers, I. M.; Cuezva, J. M.] ISCIII, CIBERER, Madrid, Spain.
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 1742-464X
J9 FEBS J
JI FEBS J.
PD SEP
PY 2012
VL 279
SU 1
SI SI
BP 313
EP 313
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 996XR
UT WOS:000308128602038
ER
PT J
AU Schmidt, C
Voss, T
Misteli, T
Jackson, S
AF Schmidt, C.
Voss, T.
Misteli, T.
Jackson, S.
TI Identification of novel chromatin modulators of the DNA damage response
SO FEBS JOURNAL
LA English
DT Meeting Abstract
CT 22nd IUBMB Congress/37th FEBS Congress
CY SEP 04-09, 2012
CL Seville, SPAIN
SP IUBMB, FEBS
C1 [Schmidt, C.; Jackson, S.] Gurdon Inst, London, England.
[Voss, T.; Misteli, T.] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1742-464X
J9 FEBS J
JI FEBS J.
PD SEP
PY 2012
VL 279
SU 1
SI SI
BP 541
EP 541
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 996XR
UT WOS:000308128602763
ER
PT J
AU Matuz, K
Motyan, J
Li, M
Wlodawer, A
Tozser, J
AF Matuz, Krisztina
Motyan, Janos
Li, Mi
Wlodawer, Alexander
Tozser, Jozsef
TI Inhibition of XMRV and HIV-1 proteases by pepstatin A and
acetyl-pepstatin
SO FEBS JOURNAL
LA English
DT Article
DE aspartic protease; crystal structure; enzyme inhibition; inhibitor
binding; retrovirus
ID HUMAN-IMMUNODEFICIENCY-VIRUS; RESOLUTION CRYSTAL-STRUCTURES; AMINO-ACID
PREFERENCES; TYPE-1 PROTEASE; RETROVIRAL PROTEASES; LEUKEMIA; MUTATIONS;
STABILITY; COMPLEXES; RESIDUES
AB The kinetic properties of two classical inhibitors of aspartic proteases (PRs), pepstatin A and acetyl-pepstatin, were compared in their interactions with HIV-1 and xenotropic murine leukemia virus related virus (XMRV) PRs. Both compounds are substantially weaker inhibitors of XMRV PR than of HIV-1 PR. Previous kinetic and structural studies characterized HIV-1 PRacetyl-pepstatin and XMRV PRpepstatin A complexes and suggested dramatically different binding modes. Interaction energies were calculated for the possible binding modes and suggested a strong preference for the one-inhibitor binding mode for HIV-1 PRacetyl-pepstatin and the two-inhibitor binding mode for XMRV PRpepstatin A interactions. Comparison of the molecular models suggested that in the case of XMRV PR the relatively unfavorable interactions at S3' and the favorable interactions at S4 and S4' sites with the statine residues may shift the ground state binding towards the two-inhibitor binding mode, whereas the single molecule ground state binding of statines to the HIV-1 PR appear to be more favorable. The preferred single molecular binding to HIV-1 PR allows the formation of the transition state complex, represented by substantially better binding constants. Intriguingly, the crystal structure of the complex of acetyl-pepstatin with XMRV PR has shown a mixed type of binding: the unusual binding mode of two molecules of the inhibitor to the enzyme, in a mode very similar to the previously determined complex with pepstatin A, together with the classical binding mode found for HIV-1 PR. The structure is thus in good agreement with the very similar interaction energies calculated for the two types of binding. Database ?The final coordinates of the crystal structure of XMRV protease complexed with acetyl-pepstatin are available in the Protein Data Bank under the accession number 4EXH Structured digital abstract HIV-1 PR and HIV-1 PR bind by biochemical (View interaction) XMRV PR cleaves MLV Gag by enzymatic study (View interaction) XMRV PR and XMRV PR bind by biochemical (View interaction) XMRV PR and XMRV PR bind by x-ray crystallography (View interaction)
C1 [Matuz, Krisztina; Motyan, Janos; Tozser, Jozsef] Univ Debrecen, Fac Med, Dept Biochem & Mol Biol, H-4012 Debrecen, Hungary.
[Li, Mi; Wlodawer, Alexander] NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick Natl Lab Canc Res, Bethesda, MD 20892 USA.
[Li, Mi] SAIC Frederick, Basic Res Program, Frederick, MD USA.
RP Tozser, J (reprint author), Univ Debrecen, Fac Med, Dept Biochem & Mol Biol, POB 6, H-4012 Debrecen, Hungary.
EM tozser@med.unideb.hu
RI Tozser, Jozsef/A-7840-2008;
OI Tozser, Jozsef/0000-0003-0274-0056; Tozser, Jozsef/0000-0001-5076-8729
FU US Department of Energy, Office of Science, Office of Basic Energy
Sciences [W-31-109-Eng-38]; TAMOP [4.2.1./B-09/1/KONV-2010-0007];
Hungarian Science and Research Fund [OTKA K68288, OTKA 101591]; NIH,
National Cancer Institute, Center for Cancer Research; National Cancer
Institute, National Institutes of Health [HHSN261200800001E]
FX We acknowledge the use of 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 W-31-109-Eng-38. The work was supported in part
by the TAMOP 4.2.1./B-09/1/KONV-2010-0007 project and by the Hungarian
Science and Research Fund (OTKA K68288, OTKA 101591). This work was also
supported in part by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research, and 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 US Government.
NR 32
TC 2
Z9 2
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1742-464X
EI 1742-4658
J9 FEBS J
JI FEBS J.
PD SEP
PY 2012
VL 279
IS 17
BP 3276
EP 3286
DI 10.1111/j.1742-4658.2012.08714.x
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 993TS
UT WOS:000307883100024
PM 22804908
ER
PT J
AU Chanock, S
AF Chanock, Stephen
TI Toward mapping the biology of the genome
SO GENOME RESEARCH
LA English
DT Article
ID WIDE ASSOCIATION; DNA; VARIANTS; ENCODE; ENCYCLOPEDIA; ELEMENTS;
PROJECT; GENES; LOCI; MAPS
AB This issue of Genome Research presents new results, methods, and tools from The ENCODE Project (ENCyclopedia of DNA Elements), which collectively represents an important step in moving beyond a parts list of the genome and promises to shape the future of genomic research. This collection sheds light on basic biological questions and frames the current debate over the optimization of tools and methodological challenges necessary to compare and interpret large complex data sets focused on how the genome is organized and regulated. In a number of instances, the authors have highlighted the strengths and limitations of current computational and technical approaches, providing the community with useful standards, which should stimulate development of new tools. In many ways, these papers will ripple through the scientific community, as those in pursuit of understanding the "regulatory genome" will heavily traverse the maps and tools. Similarly, the work should have a substantive impact on how genetic variation contributes to specific diseases and traits by providing a compendium of functional elements for follow-up study. The success of these papers should not only be measured by the scope of the scientific insights and tools but also by their ability to attract new talent to mine existing and future data.
C1 NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH,Adv Technol Ctr, Bethesda, MD 20892 USA.
RP Chanock, S (reprint author), NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH,Adv Technol Ctr, Bethesda, MD 20892 USA.
EM chanocks@mail.nlh.gov
NR 41
TC 7
Z9 7
U1 0
U2 6
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1088-9051
J9 GENOME RES
JI Genome Res.
PD SEP
PY 2012
VL 22
IS 9
SI SI
BP 1612
EP 1615
DI 10.1101/gr.144980.112
PG 4
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA 998XD
UT WOS:000308272800003
PM 22955973
ER
PT J
AU Landt, SG
Marinov, GK
Kundaje, A
Kheradpour, P
Pauli, F
Batzoglou, S
Bernstein, BE
Bickel, P
Brown, JB
Cayting, P
Chen, YW
DeSalvo, G
Epstein, C
Fisher-Aylor, KI
Euskirchen, G
Gerstein, M
Gertz, J
Hartemink, AJ
Hoffman, MM
Iyer, VR
Jung, YL
Karmakar, S
Kellis, M
Kharchenko, PV
Li, QH
Liu, T
Liu, XS
Ma, LJ
Milosavljevic, A
Myers, RM
Park, PJ
Pazin, MJ
Perry, MD
Raha, D
Reddy, TE
Rozowsky, J
Shoresh, N
Sidow, A
Slattery, M
Stamatoyannopoulos, JA
Tolstorukov, MY
White, KP
Xi, S
Farnham, PJ
Lieb, JD
Wold, BJ
Snyder, M
AF Landt, Stephen G.
Marinov, Georgi K.
Kundaje, Anshul
Kheradpour, Pouya
Pauli, Florencia
Batzoglou, Serafim
Bernstein, Bradley E.
Bickel, Peter
Brown, James B.
Cayting, Philip
Chen, Yiwen
DeSalvo, Gilberto
Epstein, Charles
Fisher-Aylor, Katherine I.
Euskirchen, Ghia
Gerstein, Mark
Gertz, Jason
Hartemink, Alexander J.
Hoffman, Michael M.
Iyer, Vishwanath R.
Jung, Youngsook L.
Karmakar, Subhradip
Kellis, Manolis
Kharchenko, Peter V.
Li, Qunhua
Liu, Tao
Liu, X. Shirley
Ma, Lijia
Milosavljevic, Aleksandar
Myers, Richard M.
Park, Peter J.
Pazin, Michael J.
Perry, Marc D.
Raha, Debasish
Reddy, Timothy E.
Rozowsky, Joel
Shoresh, Noam
Sidow, Arend
Slattery, Matthew
Stamatoyannopoulos, John A.
Tolstorukov, Michael Y.
White, Kevin P.
Xi, Simon
Farnham, Peggy J.
Lieb, Jason D.
Wold, Barbara J.
Snyder, Michael
TI ChIP-seq guidelines and practices of the ENCODE and modENCODE consortia
SO GENOME RESEARCH
LA English
DT Article
ID TRANSCRIPTION FACTOR-BINDING; GENOME-WIDE ANALYSIS; CHROMATIN
IMMUNOPRECIPITATION; DNA ASSOCIATION; PROTEIN; IDENTIFICATION; ELEMENTS;
SITES; METHYLATIONS; MACROPHAGE
AB Chromatin immunoprecipitation (ChIP) followed by high-throughput DNA sequencing (ChIP-seq) has become a valuable and widely used approach for mapping the genomic location of transcription-factor binding and histone modifications in living cells. Despite its widespread use, there are considerable differences in how these experiments are conducted, how the results are scored and evaluated for quality, and how the data and metadata are archived for public use. These practices affect the quality and utility of any global ChIP experiment. Through our experience in performing CHIP-seq experiments, the ENCODE and modENCODE consortia have developed a set of working standards and guidelines for ChIP experiments that are updated routinely. The current guidelines address antibody validation, experimental replication, sequencing depth, data and metadata reporting, and data quality assessment. We discuss how ChIP quality, assessed in these ways, affects different uses of chip-seq data. All data sets used in the analysis have been deposited for public viewing and downloading at the ENCODE (http:/ / encodeproject.org/ENCODE/) and modENCODE (http:/ /www.modencode. org/) portals.
C1 [Farnham, Peggy J.] Univ So Calif, Dept Biochem & Mol Biol, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90089 USA.
[Lieb, Jason D.] Univ N Carolina, Dept Biol, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA.
[Lieb, Jason D.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Landt, Stephen G.; Cayting, Philip; Euskirchen, Ghia; Sidow, Arend; Snyder, Michael] Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
[Marinov, Georgi K.; DeSalvo, Gilberto; Fisher-Aylor, Katherine I.; Wold, Barbara J.] CALTECH, Div Biol, Pasadena, CA 92116 USA.
[Kundaje, Anshul; Batzoglou, Serafim] Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA.
[Kheradpour, Pouya; Kellis, Manolis] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA.
[Pauli, Florencia; Gertz, Jason; Myers, Richard M.; Reddy, Timothy E.] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA.
[Bernstein, Bradley E.; Epstein, Charles; Shoresh, Noam] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
[Bickel, Peter; Brown, James B.] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA.
[Chen, Yiwen; Liu, Tao; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Gerstein, Mark; Rozowsky, Joel] Yale Univ, Computat Biol & Bioinformat Program, New Haven, CT 06511 USA.
[Hartemink, Alexander J.] Duke Univ, Dept Comp Sci, Durham, NC 27708 USA.
[Hartemink, Alexander J.] Duke Univ, Ctr Syst Biol, Durham, NC 27708 USA.
[Hoffman, Michael M.; Stamatoyannopoulos, John A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Iyer, Vishwanath R.; Kharchenko, Peter V.] Univ Texas Austin, Inst Cellular & Mol Biol, Sect Mol Genet & Microbiol, Ctr Syst & Synthet Biol, Austin, TX 78701 USA.
[Jung, Youngsook L.; Park, Peter J.; Tolstorukov, Michael Y.] Harvard Univ, Ctr Biomed Informat, Sch Med, Boston, MA 02115 USA.
[Jung, Youngsook L.; Park, Peter J.; Tolstorukov, Michael Y.] Brigham & Womens Hosp, Div Genet, Dept Med, Boston, MA 02115 USA.
[Karmakar, Subhradip; Ma, Lijia; Slattery, Matthew; White, Kevin P.] Univ Chicago, Inst Genom & Syst Biol, Chicago, IL 60637 USA.
[Li, Qunhua] Penn State Univ, Dept Stat, University Pk, PA 16802 USA.
[Milosavljevic, Aleksandar] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Pazin, Michael J.] NHGRI, NIH, Rockville, MD 20852 USA.
[Perry, Marc D.] Ontario Inst Canc Res, Toronto, ON MSG 0A3, Canada.
[Raha, Debasish] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06511 USA.
[Sidow, Arend] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA.
[Stamatoyannopoulos, John A.] Univ Washington, Dept Med, Seattle, WA 98195 USA.
[Xi, Simon] Univ Massachusetts, Sch Med, Worcester, MA 01655 USA.
RP Farnham, PJ (reprint author), Univ So Calif, Dept Biochem & Mol Biol, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90089 USA.
EM pfarnham@usc.edu; jlieb@bio.unc.edu; woldb@caltech.edu;
mpsnyder@stanford.edu
RI Hoffman, Michael/I-1924-2012; Liu, Tao/G-3585-2010; Brown,
James/H-2971-2015;
OI Farnham, Peggy/0000-0003-4469-7914; Rozowsky, Joel/0000-0002-3565-0762;
Pazin, Michael/0000-0002-7561-3640; Hoffman,
Michael/0000-0002-4517-1562; Liu, Tao/0000-0002-8818-8313; Liu,
Tao/0000-0003-0446-9001; Marinov, Georgi/0000-0003-1822-7273
FU NHGRI NIH HHS [K99 HG006698]
NR 51
TC 391
Z9 393
U1 7
U2 65
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1088-9051
J9 GENOME RES
JI Genome Res.
PD SEP
PY 2012
VL 22
IS 9
SI SI
BP 1813
EP 1831
DI 10.1101/gr.136184.111
PG 19
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA 998XD
UT WOS:000308272800021
PM 22955991
ER
PT J
AU Feldman, BM
Berger, K
Bohn, R
Carcao, M
Fischer, K
Gringeri, A
Hoots, K
Mantovani, L
Willan, AR
Schramm, W
AF Feldman, B. M.
Berger, K.
Bohn, R.
Carcao, M.
Fischer, K.
Gringeri, A.
Hoots, K.
Mantovani, L.
Willan, A. R.
Schramm, W.
TI Haemophilia prophylaxis: how can we justify the costs?
SO HAEMOPHILIA
LA English
DT Article
DE cost; haemophilia; prophylaxis; treatment; willingness to pay
ID WILLINGNESS-TO-PAY; QUALITY-OF-LIFE; CLOTTING FACTOR; ON-DEMAND;
TAILORED PROPHYLAXIS; DEVELOPING-COUNTRIES; ECONOMIC-EVALUATION; FACTOR
REPLACEMENT; TREATMENT CENTERS; UTILITY ANALYSIS
AB . Severe haemophilia results in increased mortality and poorer quality of life. Factor prophylaxis leads to a more normal life, but is very costly; most of the cost is due to the high cost of replacement factor. Despite its high cost, factor prophylaxis has been adopted throughout the developed world even in different health care systems. We argue that there are at least five possible reasons why societies may value factor prophylaxis despite its cost: (i) it is directed towards an inherited disease, (ii) the treatment is largely directed towards children, (iii) the disease is rare and the overall cost to society is small, (iv) the treatment is preventative, and v) the high cost is largely the result of providing safe products. In an era of rising health care costs, there is a strong research agenda to establish the factors that determine the value of expensive therapies for rare diseases like haemophilia.
C1 [Feldman, B. M.] Univ Toronto, Hosp Sick Children, Div Rheumatol, Dept Pediat,Inst Hlth Policy Management & Evaluat, Toronto, ON M5G 1X8, Canada.
[Feldman, B. M.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON M5G 1X8, Canada.
[Berger, K.] Univ Hosp Munich, Dept Homeostasis & Transfus Med, Munich, Germany.
[Bohn, R.] Rhonda L Bohn LLC, Waban, MA USA.
[Carcao, M.] Univ Toronto, Hosp Sick Children, Div Hematol Oncol, Toronto, ON M5G 1X8, Canada.
[Carcao, M.] Univ Toronto, Dept Pediat, Toronto, ON M5G 1X8, Canada.
[Fischer, K.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
[Fischer, K.] Univ Med Ctr Utrecht, Creveldkliniek, Utrecht, Netherlands.
[Gringeri, A.] IRCCS Ca Granda Osped Maggiore Policlin, Dept Med & Med Special, Milan, Italy.
[Gringeri, A.] Univ Milan, Milan, Italy.
[Hoots, K.] NHLBI, NIH, Div Blood Dis & Resources, Bethesda, MD 20892 USA.
[Mantovani, L.] Univ Naples Federico II, CIRFF Ctr Pharmacoecon, Naples, Italy.
[Willan, A. R.] Dalla Lana Sch Publ Hlth, Div Biostat, Toronto, ON, Canada.
[Willan, A. R.] SickKids Res Inst, Child Hlth Evaluat Sci, Toronto, ON, Canada.
[Schramm, W.] Univ Munich, Haemophilia Ctr, Munich, Germany.
RP Feldman, BM (reprint author), Univ Toronto, Hosp Sick Children, Div Rheumatol, Dept Pediat,Inst Hlth Policy Management & Evaluat, 555 Univ Ave, Toronto, ON M5G 1X8, Canada.
EM brian.feldman@sickkids.ca
OI Mantovani, Lorenzo Giovanni/0000-0003-3866-8199
FU Bayer HealthCare Pharmaceuticals Inc.; Baxter BioScience; CSL Behring;
Novo Nordisk; Pfizer Inc.; Bayer Inc.; Baxter HealthCare Corporation;
Baxter; Pfizer; Biotest; Bayer; Wyeth/Pfizer
FX This work was initiated at a meeting supported by unrestricted grants
from Bayer HealthCare Pharmaceuticals Inc.; Baxter BioScience; CSL
Behring; Novo Nordisk, and Pfizer Inc. administered through The Hospital
for Sick Children Foundation, Toronto, Canada. The authors would like to
express recognition to the International Prophylaxis Study Group (IPSG)
Steering Committee: Victor S. Blanchette (Chair), Rolf Ljung (Co-Chair),
Louis M. Aledort (Co-Chair), Marijke van den Berg, Brian M. Feldman,
Alessandro Gringeri, Marilyn Manco-Johnson, Pia Petrini, Georges E.
Rivard, Wolfgang Schramm, for their continuous scientific incentive and
advice.; BF currently holds investigator initiated peer-reviewed grants
from Bayer Inc. and the Baxter HealthCare Corporation. RB has acted as a
paid consultant to Baxter BioScience, Pfizer, Inc. and Novo Nordisk, but
has received for funding for this work. KF has received speaker's fees
from Baxter, Pfizer, Novo Nordisk, Biotest; has performed consultancy
for Baxter, Biogen and Novo Nordisk; and has received research support
from Bayer, Wyeth/Pfizer, Baxter and Novo Nordisk. All other authors
have declared no conflicting interests.
NR 65
TC 10
Z9 10
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1351-8216
EI 1365-2516
J9 HAEMOPHILIA
JI Haemophilia
PD SEP
PY 2012
VL 18
IS 5
BP 680
EP 684
DI 10.1111/j.1365-2516.2012.02790.x
PG 5
WC Hematology
SC Hematology
GA 993ZT
UT WOS:000307900700022
PM 22507524
ER
PT J
AU Loomba, R
Abraham, M
Unalp, A
Wilson, L
Lavine, J
Doo, E
Bass, NM
AF Loomba, Rohit
Abraham, Maria
Unalp, Aynur
Wilson, Laura
Lavine, Joel
Doo, Ed
Bass, Nathan M.
CA Nonalcoholic Steatohepatitis
TI Association between diabetes, family history of diabetes, and risk of
nonalcoholic steatohepatitis and fibrosis
SO HEPATOLOGY
LA English
DT Article
ID FATTY LIVER-DISEASE; INSULIN-RESISTANCE; NATURAL-HISTORY;
HEPATOCELLULAR-CARCINOMA; AMINOTRANSFERASE LEVELS; CRYPTOGENIC
CIRRHOSIS; UNITED-STATES; VITAMIN-E; SEVERITY; PIOGLITAZONE
AB Previous studies have shown familial aggregation of insulin resistance and nonalcoholic fatty liver disease (NAFLD). Therefore, we aimed to examine whether family history of diabetes mellitus (DM) is associated with nonalcoholic steatohepatitis (NASH) and fibrosis in patients with NAFLD. This was a cross-sectional analysis in participants of the NAFLD Database study and PIVENS trial who had available data on family history of DM. One thousand and sixty-nine patients (63% women), with mean age of 49.6 (+/- 11.8) years and body mass index (BMI) of 34.2 (+/- 6.4) kg/m2, were included. Thirty percent had DM, and 56% had a family history of DM. Both personal history of DM and family history of DM were significantly associated with NASH, with an odds ratio (OR) of 1.93 (95% confidence interval [CI]: 1.37-2.73; P <0.001) and 1.48 (95% CI: 1.11-1.97; P = 0.01) and any fibrosis with an OR of 3.31 (95% CI: 2.26-4.85; P < 0.001) and 1.66 (95% CI: 1.25-2.20; P < 0.001), respectively. When the models were adjusted for age, sex, BMI, ethnicity, and metabolic traits, the association between diabetes and family history of DM with NASH showed an increased adjusted OR of 1.76 (95% CI: 1.13-2.72; P < 0.001) and 1.34 (95% CI: 0.99-1.81; P = 0.06), respectively, and with any fibrosis with a significant adjusted OR of 2.57 (95% CI: 1.61-4.11; P < 0.0001) and 1.38 (95% CI: 1.02-1.87; P = 0.04), respectively. After excluding patients with personal history of diabetes, family history of DM was significantly associated with the presence of NASH and any fibrosis with an adjusted OR of 1.51 (95% CI: 1.01-2.25; P = 0.04) and 1.49 (95% CI: 1.01-2.20; P = 0.04), respectively. Conclusions: Diabetes is strongly associated with risk of NASH, fibrosis, and advanced fibrosis. Family history of diabetes, especially among nondiabetics, is associated with NASH and fibrosis in NAFLD. (HEPATOLOGY 2012;56:943951)
C1 [Loomba, Rohit] Univ Calif San Diego, Dept Med, Div Gastroenterol, La Jolla, CA 92093 USA.
[Loomba, Rohit] Univ Calif San Diego, Dept Family & Prevent Med, Div Epidemiol, La Jolla, CA 92093 USA.
[Abraham, Maria; Unalp, Aynur; Wilson, Laura] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Lavine, Joel] Columbia Univ, Div Pediat Gastroenterol, New York, NY USA.
[Doo, Ed] NIDDKD, Liver Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Bass, Nathan M.] Univ Calif San Francisco, Div Gastroenterol & Hepatol, San Francisco, CA 94143 USA.
RP Loomba, R (reprint author), Univ Calif San Diego, Sch Med, Div Gastroenterol & Epidemiol, UC 303,MC-0063,9500 Gilman Dr, La Jolla, CA 92093 USA.
EM roloomba@ucsd.edu
RI Vaughn, Ivana/B-6138-2016
OI Vaughn, Ivana/0000-0002-7201-0289
FU American Gastroenterological Association (AGA)
Foundation-Sucampo-Association of Specialty Professors Designated
Research Award in Geriatric Gastroenterology; T. Franklin Williams
Scholarship Award; Atlantic Philanthropies, Inc.; John A. Hartford
Foundation; Association of Specialty Professors; AGA; UCSD Digestive
Diseases Research Development Center (U.S. PHS) [DK080506]; National
Institute of Diabetes and Digestive and Kidney Diseases [U01DK061718,
U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737,
U01DK061738, U01DK061730, U01DK061713]; National Institute of Child
Health and Human Development; National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK), National Institutes of Health;
[K23DK090303]
FX This work was supported, in part, by the American Gastroenterological
Association (AGA) Foundation-Sucampo-Association of Specialty Professors
Designated Research Award in Geriatric Gastroenterology and by a T.
Franklin Williams Scholarship Award, with funding provided by Atlantic
Philanthropies, Inc., the John A. Hartford Foundation, the Association
of Specialty Professors, and the AGA and K23DK090303 (to R. L.). This
research was funded, in part, with the support of the UCSD Digestive
Diseases Research Development Center (U.S. PHS grant no.: DK080506). The
Nonalcoholic Steatohepatitis Clinical Research Network is supported by
the National Institute of Diabetes and Digestive and Kidney Diseases
(grant nos.: U01DK061718, U01DK061728, U01DK061731, U01DK061732,
U01DK061734, U01DK061737, U01DK061738, U01DK061730, and U01DK061713) and
by the National Institute of Child Health and Human Development.; The
study was sponsored by the National Institute of Diabetes and Digestive
and Kidney Diseases (NIDDK), National Institutes of Health. As per the
policy of the network, the manuscript for this article was reviewed by
the NIDDK before publication. The authors take complete responsibility
of the data analyses and credibility of findings.
NR 28
TC 86
Z9 88
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD SEP
PY 2012
VL 56
IS 3
BP 943
EP 951
DI 10.1002/hep.25772
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 995WX
UT WOS:000308046700018
PM 22505194
ER
PT J
AU Kong, XN
Feng, DC
Wang, H
Hong, F
Bertola, A
Wang, FS
Gao, B
AF Kong, Xiaoni
Feng, Dechun
Wang, Hua
Hong, Feng
Bertola, Adeline
Wang, Fu-Sheng
Gao, Bin
TI Interleukin-22 induces hepatic stellate cell senescence and restricts
liver fibrosis in mice
SO HEPATOLOGY
LA English
DT Article
ID P53; INFLAMMATION; HEPATOCYTES; APOPTOSIS; IL-22
AB Interleukin (IL)-22 is known to play a key role in promoting antimicrobial immunity, inflammation, and tissue repair at barrier surfaces by binding to the receptors, IL-10R2 and IL-22R1. IL-22R1 is generally thought to be expressed exclusively in epithelial cells. In this study, we identified high levels of IL-10R2 and IL-22R1 expression on hepatic stellate cells (HSCs), the predominant cell type involved in liver fibrogenesis in response to liver damage. In vitro treatment with IL-22 induced the activation of signal transducer and activator of transcription (STAT) 3 in primary mouse and human HSCs. IL-22 administration prevented HSC apoptosis in vitro and in vivo, but surprisingly, the overexpression of IL-22 by either gene targeting (e.g., IL-22 transgenic mice) or exogenous administration of adenovirus expressing IL-22 reduced liver fibrosis and accelerated the resolution of liver fibrosis during recovery. Furthermore, IL-22 overexpression or treatment increased the number of senescence-associated beta-galactosidase-positive HSCs and decreased alpha-smooth muscle actin expression in fibrotic livers in vivo and cultured HSCs in vitro. Deletion of STAT3 prevented IL-22-induced HSC senescence in vitro, whereas the overexpression of a constitutively activated form of STAT3 promoted HSC senescence through p53- and p21-dependent pathways. Finally, IL-22 treatment up-regulated the suppressor of cytokine signaling (SOCS) 3 expression in HSCs. Immunoprecipitation analyses revealed that SOCS3 bound p53 and subsequently increased the expression of p53 and its target genes, contributing to IL-22-mediated HSC senescence. Conclusion: IL-22 induces the senescence of HSCs, which express both IL-10R2 and IL-22R1, thereby ameliorating liver fibrogenesis. The antifibrotic effect of IL-22 is likely mediated by the induction of HSC senescence, in addition to the previously discovered hepatoprotective functions of IL-22. (HEPATOLOGY 2012;56:11501159)
C1 [Kong, Xiaoni; Feng, Dechun; Wang, Hua; Bertola, Adeline; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA.
[Hong, Feng] Mt Sinai Sch Med, New York, NY USA.
[Wang, Fu-Sheng] Beijing 302 Hosp, Res Ctr Biol Therapy, Beijing, Peoples R China.
RP Gao, B (reprint author), NIAAA, Lab Liver Dis, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA.
EM bgao@mail.nih.gov
RI Feng, Dechun/Q-5962-2016;
OI Bertola, Adeline/0000-0002-4885-8423
FU National Institute on Alcohol Abuse and Alcoholism, National Institutes
of Health
FX This work was supported by the intramural program of the National
Institute on Alcohol Abuse and Alcoholism, National Institutes of
Health. The authors thank Dr. Michitaka Ozaki (Hokkaido University,
Sapporo, Japan) for providing the caSTAT3 adenovirus and also Drs.
Mingquan Zheng and Jay K. Kolls (Louisiana State University, New
Orleans, LA) for providing IL-22 adenovirus and also thank Dr. Scott
Friedman (Mount Sinai School of Medicine, New York) for providing the
LX2 cells.
NR 26
TC 99
Z9 109
U1 2
U2 27
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD SEP
PY 2012
VL 56
IS 3
BP 1150
EP 1159
DI 10.1002/hep.25744
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 995WX
UT WOS:000308046700038
PM 22473749
ER
PT J
AU Arias, IM
AF Arias, Irwin M.
TI In Memoriam: Nelson Fausto, M.D.
SO HEPATOLOGY
LA English
DT Biographical-Item
C1 NIH, Bethesda, MD 20892 USA.
RP Arias, IM (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
EI 1527-3350
J9 HEPATOLOGY
JI Hepatology
PD SEP
PY 2012
VL 56
IS 3
BP 1187
EP 1188
DI 10.1002/hep.25974
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 995WX
UT WOS:000308046700049
ER
PT J
AU Dong, S
Kurtis, JD
Pond-Tor, S
Kabyemela, E
Duffy, PE
Fried, M
AF Dong, Shu
Kurtis, Jonathan D.
Pond-Tor, Sunthorn
Kabyemela, Edward
Duffy, Patrick E.
Fried, Michal
TI CXC Ligand 9 Response to Malaria during Pregnancy Is Associated with
Low-Birth-Weight Deliveries
SO INFECTION AND IMMUNITY
LA English
DT Article
ID PLACENTAL MALARIA; IFN-GAMMA; INFECTION; CHEMOKINE; WOMEN; EXPRESSION;
EPIDEMIOLOGY; INTERFERON; CYTOKINES; IMMUNITY
AB Placental infection with Plasmodium falciparum is associated with increased levels of proinflammatory cytokines, including tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma), and previous studies have associated increased levels of these cytokines with low birth weight (LBW), especially for malaria-infected primigravidae. To define the contribution of TNF-alpha and IFN-gamma networks to placental-malaria-associated LBW, we measured chemokines induced by TNF-alpha and IFN-gamma and related them to birth weight in a birth cohort of 782 mother-infant pairs residing in an area of P. falciparum holoendemicity in Tanzania. Among primigravidae, levels of CCL2, CXC ligand 9 (CXCL9), and CXCL13 were significantly higher during malaria infection in both the placenta and peripheral blood. Placental CXCL9 and CXCL13 levels were also higher in placental blood from secundigravidae and multigravidae. In multivariate analyses adjusted for known predictors of birth weight, malaria-infected primigravidae with placental CXCL9 levels in the lowest tertile gave birth to babies who weighed 610 g more than babies born to mothers with high CXCL9 levels. CXCL9 expression is induced by IFN-gamma, and the strong association between birth weight and placental CXCL9 is consistent with previous observations relating IFN-gamma to poor pregnancy outcomes.
C1 [Kabyemela, Edward; Duffy, Patrick E.; Fried, Michal] Seattle Biomed Res Inst, Mother Offspring Malaria Studies Project Tanzania, Seattle, WA 98109 USA.
[Kurtis, Jonathan D.; Pond-Tor, Sunthorn] Brown Univ, Rhode Isl Hosp, Sch Med, Ctr Int Hlth Res, Providence, RI 02903 USA.
[Duffy, Patrick E.; Fried, Michal] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD USA.
RP Fried, M (reprint author), Seattle Biomed Res Inst, Mother Offspring Malaria Studies Project Tanzania, 4 Nickerson St, Seattle, WA 98109 USA.
EM michal.fried@nih.gov
FU U.S. National Institutes of Health [AI52059, HD058005]; Bill & Melinda
Gates Foundation [47029]; Intramural Research Program of NIAID-NIH
FX This work was supported by grants from the U.S. National Institutes of
Health (grants AI52059 to P.E.D. and HD058005 to M.F.) and the Bill &
Melinda Gates Foundation (grant 47029 to P.E.D.). This research was
supported in part by the Intramural Research Program of NIAID-NIH.
NR 28
TC 10
Z9 11
U1 0
U2 4
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 2012
VL 80
IS 9
BP 3034
EP 3038
DI 10.1128/IAI.00220-12
PG 5
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 993ON
UT WOS:000307869100006
PM 22689822
ER
PT J
AU Bridge, DR
Martin, KH
Moore, ER
Lee, WM
Carroll, JA
Rocha, CL
Olson, JC
AF Bridge, Dacie R.
Martin, Karen H.
Moore, Elizabeth R.
Lee, Wendy M.
Carroll, James A.
Rocha, Claudia L.
Olson, Joan C.
TI Examining the Role of Actin-Plasma Membrane Association in Pseudomonas
aeruginosa Infection and Type III Secretion Translocation in Migratory
T24 Epithelial Cells
SO INFECTION AND IMMUNITY
LA English
DT Article
ID GTPASE-ACTIVATING PROTEIN; EXOENZYME-S; ADP-RIBOSYLATION;
EZRIN/RADIXIN/MOESIN PROTEINS; CYTOSKELETON DISRUPTION; DEPENDENT
TRANSLOCATION; EXOT CONTRIBUTES; LEADING-EDGE; IN-VITRO; INVASION
AB The opportunistic pathogen Pseudomonas aeruginosa targets wounded epithelial barriers, but the cellular alteration that increases susceptibility to P. aeruginosa infection remains unclear. This study examined how cell migration contributes to the establishment of P. aeruginosa infections using (i) highly migratory T24 epithelial cells as a cell culture model, (ii) mutations in the type III secretion (T3S) effector ExoS to manipulate P. aeruginosa infection, and (iii) high-resolution immunofluorescent microscopy to monitor ExoS translocation. ExoS includes both GTPase-activating (GAP) and ADP-ribosyltransferase (ADPRT) activities, and P. aeruginosa cells expressing wild-type ExoS preferentially bound to the leading edge of T24 cells, where ExoS altered leading-edge architecture and actin anchoring in conjunction with interrupting T3S translocation. Inactivation of ExoS GAP activity allowed P. aeruginosa to be internalized and secrete ExoS within T24 cells, but as with wild-type ExoS, translocation was limited in association with disruption of actin anchoring. Inactivation of ExoS ADPRT activity resulted in significantly enhanced T3S translocation by P. aeruginosa cells that remained extracellular and in conjunction with maintenance of actin-plasma membrane association. Infection with P. aeruginosa expressing ExoS lacking both GAP and ADPRT activities resulted in the highest level of T3S translocation, and this occurred in conjunction with the entry and alignment of P. aeruginosa and ExoS along actin filaments. Collectively, in using ExoS mutants to modulate and visualize T3S translocation, we were able to (i) confirm effector secretion by internalized P. aeruginosa, (ii) differentiate the mechanisms underlying the effects of ExoS GAP and ADPRT activities on P. aeruginosa internalization and T3S translocation, (iii) confirm that ExoS ADPRT activity targeted a cellular substrate that interrupted T3S translocation, (iv) visualize the ability of P. aeruginosa and ExoS to align with actin filaments, and (v) demonstrate an association between actin anchoring at the leading edge of T24 cells and the establishment of P. aeruginosa infection. Our studies also highlight the contribution of ExoS to the opportunistic nature of P. aeruginosa infection through its ability to exert cytotoxic effects that interrupt T3S translocation and P. aeruginosa internalization, which in turn limit the P. aeruginosa infectious process.
C1 [Bridge, Dacie R.; Martin, Karen H.; Moore, Elizabeth R.; Lee, Wendy M.; Olson, Joan C.] W Virginia Univ, Hlth Sci Ctr, Dept Microbiol Immunol & Cell Biol, Morgantown, WV 26506 USA.
[Martin, Karen H.] W Virginia Univ, Hlth Sci Ctr, Dept Neurobiol & Anat, Morgantown, WV 26506 USA.
[Martin, Karen H.] W Virginia Univ, Hlth Sci Ctr, Mary Babb Randolph Canc Ctr, Morgantown, WV 26506 USA.
[Carroll, James A.] NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA.
[Rocha, Claudia L.] The Citadel, Dept Biol, Charleston, SC USA.
RP Olson, JC (reprint author), W Virginia Univ, Hlth Sci Ctr, Dept Microbiol Immunol & Cell Biol, Morgantown, WV 26506 USA.
EM joolson@hsc.wvu.edu
OI Bridge, Dacie/0000-0001-9048-0594
FU NIH [P20 RR016440]; National Center for Research Resources [P20
RR016477]; Mary Babb Randolph Cancer Center
FX Imaging experiments and image analysis were performed in the West
Virginia University Imaging Facility, which is supported in part by the
Mary Babb Randolph Cancer Center and NIH grant P20 RR016440.; Our
studies were funded in part through grant P20 RR016477 from the National
Center for Research Resources, awarded to the West Virginia IDeA Network
for Biomedical Research Excellence.
NR 69
TC 3
Z9 3
U1 0
U2 4
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 2012
VL 80
IS 9
BP 3049
EP 3064
DI 10.1128/IAI.00231-12
PG 16
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 993ON
UT WOS:000307869100008
PM 22689823
ER
PT J
AU Jain, S
Sutchu, S
Rosa, PA
Byram, R
Jewett, MW
AF Jain, Sunny
Sutchu, Selina
Rosa, Patricia A.
Byram, Rebecca
Jewett, Mollie W.
TI Borrelia burgdorferi Harbors a Transport System Essential for Purine
Salvage and Mammalian Infection
SO INFECTION AND IMMUNITY
LA English
DT Article
ID LYME-DISEASE SPIROCHETE; BACILLUS-SUBTILIS; ESCHERICHIA-COLI; PURR
REGULON; PROTEIN; PLASMID; CYCLE; OSPC; PREDICTION; CHITOBIOSE
AB Borrelia burgdorferi is the tick-borne bacterium that causes the multistage inflammatory disease Lyme disease. B. burgdorferi has a reduced genome and lacks the enzymes required for de novo synthesis of purines for synthesis of RNA and DNA. Therefore, this obligate pathogen is dependent upon the tick vector and mammalian host environments for salvage of purine bases for nucleic acid biosynthesis. This pathway is vital for B. burgdorferi survival throughout its infectious cycle, as key enzymes in the purine salvage pathway are essential for the ability of the spirochete to infect mice and critical for spirochete replication in the tick. The transport of preformed purines into the spirochete is the first step in the purine salvage pathway and may represent a novel therapeutic target and/or means to deliver antispirochete molecules to the pathogen. However, the transport systems critical for purine salvage by B. burgdorferi have yet to be identified. Herein, we demonstrate that the genes bbb22 and bbb23, present on B. burgdorferi's essential plasmid circular plasmid 26 (cp26), encode key purine transport proteins. BBB22 and/or BBB23 is essential for hypoxanthine transport and contributes to the transport of adenine and guanine. Furthermore, B. burgdorferi lacking bbb22-23 was noninfectious in mice up to a dose of 1 x 10(7) spirochetes. Together, our data establish that bbb22-23 encode purine permeases critical for B. burgdorferi mammalian infectivity, suggesting that this transport system may serve as a novel antimicrobial target for the treatment of Lyme disease.
C1 [Jain, Sunny; Sutchu, Selina; Jewett, Mollie W.] Univ Cent Florida, Coll Med, Burnett Sch Biomed Sci, Orlando, FL 32816 USA.
[Rosa, Patricia A.; Byram, Rebecca] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT USA.
RP Jewett, MW (reprint author), Univ Cent Florida, Coll Med, Burnett Sch Biomed Sci, Orlando, FL 32816 USA.
EM Mollie.Jewett@ucf.edu
FU NIH, NIAID [5K22AI081739]; UCF
FX This work was supported by UCF startup funds and grant 5K22AI081739 from
NIH, NIAID, to M.W.J.
NR 42
TC 10
Z9 10
U1 1
U2 3
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 2012
VL 80
IS 9
BP 3086
EP 3093
DI 10.1128/IAI.00514-12
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 993ON
UT WOS:000307869100011
PM 22710875
ER
PT J
AU Frank, KM
Zhou, T
Moreno-Vinasco, L
Hollett, B
Garcia, JGN
Wardenburg, JB
AF Frank, Karen M.
Zhou, Tong
Moreno-Vinasco, Liliana
Hollett, Brian
Garcia, Joe G. N.
Wardenburg, Juliane Bubeck
TI Host Response Signature to Staphylococcus aureus Alpha-Hemolysin
Implicates Pulmonary Th17 Response
SO INFECTION AND IMMUNITY
LA English
DT Article
ID PANTON-VALENTINE LEUKOCIDIN; INNATE IMMUNE-SYSTEM; HYPER-IGE SYNDROME;
AIRWAYS IN-VIVO; NEUTROPHIL RECRUITMENT; EXTRACELLULAR-MATRIX;
ENDOTHELIAL-CELLS; ADAPTIVE IMMUNITY; CXC CHEMOKINE; PNEUMONIA
AB Staphylococcus aureus pneumonia causes significant morbidity and mortality. Alpha-hemolysin (Hla), a pore-forming cytotoxin of S. aureus, has been identified through animal models of pneumonia as a critical virulence factor that induces lung injury. In spite of considerable molecular knowledge of how this cytotoxin injures the host, the precise host response to Hla in the context of infection remains poorly understood. We employed whole-genome expression profiling of infected lungs to define the host response to wild-type S. aureus compared with the response to an Hla-deficient isogenic mutant in experimental pneumonia. These data provide a complete expression profile at 4 and at 24 h postinfection, revealing a unique response to the toxin-expressing strain. Gene ontogeny analysis revealed significant differences in the extracellular matrix and cardiomyopathy pathways, both of which govern cellular interactions in the tissue microenvironment. Evaluation of individual transcript responses to Hla-secreting staphylococci was notable for upregulation of host cytokine and chemokine genes, including the p19 subunit of interleukin-23. Consistent with this observation, the cellular immune response to infection was characterized by a prominent Th17 response to the wild-type pathogen. These findings define specific host mRNA responses to Hla-producing S. aureus, coupling the pulmonary Th17 response to the secretion of this cytotoxin. Expression profiling to define the host response to a single virulence factor proved to be a valuable tool in identifying pathways for further investigation in S. aureus pneumonia. This approach may be broadly applicable to the study of bacterial toxins, defining host pathways that can be targeted to mitigate toxin-induced disease.
C1 [Frank, Karen M.; Hollett, Brian] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA.
[Zhou, Tong; Moreno-Vinasco, Liliana; Garcia, Joe G. N.] Univ Illinois, Inst Personalized Resp Med, Sect Pulm Crit Care Sleep & Allergy, Chicago, IL USA.
[Wardenburg, Juliane Bubeck] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA.
[Wardenburg, Juliane Bubeck] Univ Chicago, Dept Microbiol, Chicago, IL 60637 USA.
RP Frank, KM (reprint author), NIH, Dept Lab Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM karen.frank@nih.gov; jbubeckw@peds.bsd.uchicago.edu
FU Departments of Pathology, Pediatrics, and Microbiology at the University
of Chicago; National Institute of Allergy and Infectious Diseases
[AI097434]; Region V Great Lakes RCE (NIH) [2-U54-AI-057153]
FX This work was supported by the Departments of Pathology, Pediatrics, and
Microbiology at the University of Chicago and a grant from the National
Institute of Allergy and Infectious Diseases to J.B.W. (grant AI097434).
J.B.W. also acknowledges membership in and support from the Region V
Great Lakes RCE (NIH award 2-U54-AI-057153).
NR 77
TC 23
Z9 24
U1 0
U2 5
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 2012
VL 80
IS 9
BP 3161
EP 3169
DI 10.1128/IAI.00191-12
PG 9
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 993ON
UT WOS:000307869100017
PM 22733574
ER
PT J
AU Goudar, SS
Carlo, WA
McClure, EM
Pasha, O
Patel, A
Esamai, F
Chomba, E
Garces, A
Althabe, F
Kodkany, B
Sami, N
Derman, RJ
Hibberd, PL
Liechty, EA
Krebs, NF
Hambidge, KM
Buekens, P
Moore, J
Wallace, D
Jobe, AH
Koso-Thomas, M
Wright, LL
Goldenberg, RL
AF Goudar, Shivaprasad S.
Carlo, Waldemar A.
McClure, Elizabeth M.
Pasha, Omrana
Patel, Archana
Esamai, Fabian
Chomba, Elwyn
Garces, Ana
Althabe, Fernando
Kodkany, Bhalachandra
Sami, Neelofar
Derman, Richard J.
Hibberd, Patricia L.
Liechty, Edward A.
Krebs, Nancy F.
Hambidge, K. Michael
Buekens, Pierre
Moore, Janet
Wallace, Dennis
Jobe, Alan H.
Koso-Thomas, Marion
Wright, Linda L.
Goldenberg, Robert L.
TI The Maternal and Newborn Health Registry Study of the Global Network for
Women's and Children's Health Research
SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS
LA English
DT Article
DE Maternal mortality; Neonatal mortality; Perinatal mortality; Pregnancy;
Registry; Stillbirth
ID DEVELOPING-COUNTRIES; PERINATAL-MORTALITY; NEONATAL DEATHS; OBSTETRIC
CARE; STILLBIRTH; SETTINGS; TRIAL
AB Objective: To implement a vital statistics registry system to register pregnant women and document birth outcomes in the Global Network for Women's and Children's Health Research sites in Asia, Africa, and Latin America. Methods: The Global Network sites began a prospective population-based pregnancy registry to identify all pregnant women and record pregnancy outcomes up to 42 days post-delivery in more than 100 defined low-resource geographic areas (clusters). Pregnant women were registered during pregnancy, with 42-day maternal and neonatal follow-up recorded including care received during the pregnancy and postpartum periods. Recorded outcomes included stillbirth, neonatal mortality, and maternal mortality rates. Results: In 2010, 72848 pregnant women were enrolled and 6-week follow-up was obtained for 97.8%. Across sites, 40.7%, 24.8%, and 34.5% of births occurred in a hospital, health center, and home setting, respectively. The mean neonatal mortality rate was 23 per 1000 live births, ranging from 8.2 to 48.5 per 1000 live births. The mean stillbirth rate ranged from 13.7 to 54.4 per 1000 births. Conclusion: The registry is an ongoing study to assess the impact of interventions and trends regarding pregnancy outcomes and measures of care to inform public health. ClinicalTrial.gov Trial Registration: NCT01073475 (C) 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
C1 [Carlo, Waldemar A.] Univ Alabama Birmingham, Dept Pediat, Women & Infants Ctr 9380, Birmingham, AL 35233 USA.
[Goudar, Shivaprasad S.; Kodkany, Bhalachandra] Jawaharlal Nehru Med Coll, Dept Med Educ, Belgaum, India.
[McClure, Elizabeth M.; Moore, Janet; Wallace, Dennis] Res Triangle Inst, Dept Stat & Epidemiol, Durham, NC USA.
[Pasha, Omrana; Sami, Neelofar] Aga Khan Univ, Dept Community Hlth Sci & Family Med, Karachi, Pakistan.
[Patel, Archana] Indira Gandhi Govt Med Coll, Dept Pediat, Nagpur, Maharashtra, India.
[Esamai, Fabian] Moi Univ, Sch Med, Dept Pediat, Eldoret, Kenya.
[Chomba, Elwyn] Univ Teaching Hosp, Dept Pediat, Lusaka, Zambia.
[Garces, Ana] El Inst Multidisciplinario Salud, Guatemala City, Guatemala.
[Althabe, Fernando] Univ Buenos Aires, Inst Clin Effectiveness & Hlth Policy, Buenos Aires, DF, Argentina.
[Derman, Richard J.] Christiana Care Hlth Syst, Dept Obstet & Gynecol, Newark, NJ USA.
[Hibberd, Patricia L.] Massachusetts Gen Hosp Children, Dept Pediat, Boston, MA USA.
[Liechty, Edward A.] Indiana Univ, Dept Pediat, Indianapolis, IN USA.
[Krebs, Nancy F.] Univ Colorado, Dept Pediat Nutr, Denver, CO 80202 USA.
[Hambidge, K. Michael] Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA USA.
[Buekens, Pierre; Jobe, Alan H.] Univ Cincinnati, Dept Pediat, Cincinnati, OH 45221 USA.
[Koso-Thomas, Marion; Wright, Linda L.] Eunice Kennedy Shiver Natl Inst Child Hlth & Huma, Ctr Res Mothers & Children, Bethesda, MD USA.
[Goldenberg, Robert L.] Columbia Univ, Dept Obstet & Gynecol, New York, NY USA.
RP Carlo, WA (reprint author), Univ Alabama Birmingham, Dept Pediat, Women & Infants Ctr 9380, 1700 6th Ave S, Birmingham, AL 35233 USA.
EM wcarlo@peds.uab.edu
OI GOUDAR, SHIVAPRASAD/0000-0002-8680-7053
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development of the US National Institutes of Health [U01 HD040477, U01
HD043475, U01 HD043464, U01 HD040657, U01 HD042372, U01 HD040607, U01
HD040636, U01 HD040574]
FX The project was funded by grants (U01 HD040477, U01 HD043475, U01
HD043464, U01 HD040657, U01 HD042372, U01 HD040607, U01 HD040636, U01
HD040574) from the Eunice Kennedy Shriver National Institute of Child
Health and Human Development of the US National Institutes of Health.
NR 19
TC 41
Z9 41
U1 1
U2 3
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 2012
VL 118
IS 3
BP 190
EP 193
DI 10.1016/j.ijgo.2012.04.022
PG 4
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 992QJ
UT WOS:000307794500004
PM 22738806
ER
PT J
AU Henderson, TO
Rajaraman, P
Stovall, M
Constine, LS
Olive, A
Smith, SA
Mertens, A
Meadows, A
Neglia, JP
Hammond, S
Whitton, J
Inskip, PD
Robison, LL
Diller, L
AF Henderson, Tara O.
Rajaraman, Preetha
Stovall, Marilyn
Constine, Louis S.
Olive, Aliza
Smith, Susan A.
Mertens, Ann
Meadows, Anna
Neglia, Joseph P.
Hammond, Sue
Whitton, John
Inskip, Peter D.
Robison, Leslie L.
Diller, Lisa
TI Risk Factors Associated With Secondary Sarcomas in Childhood Cancer
Survivors: A Report From the Childhood Cancer Survivor Study
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
DE Childhood cancer survivors; Secondary sarcomas; Radiation late effects
ID 2ND MALIGNANT NEOPLASMS; SOFT-TISSUE SARCOMA; BREAST-CANCER; 5-YEAR
SURVIVORS; LATE MORTALITY; BONE SARCOMAS; SOLID TUMORS; RADIATION;
CHEMOTHERAPY; RADIOTHERAPY
AB Purpose: Childhood cancer survivors have an increased risk of secondary sarcomas. To better identify those at risk, the relationship between therapeutic dose of chemotherapy and radiation and secondary sarcoma should be quantified.
Methods and Materials: We conducted a nested case-control study of secondary sarcomas (105 cases, 422 matched controls) in a cohort of 14,372 childhood cancer survivors. Radiation dose at the second malignant neoplasm (SMN) site and use of chemotherapy were estimated from detailed review of medical records. Odds ratios (ORs) and 95% confidence intervals were estimated by conditional logistic regression. Excess odds ratio (EOR) was modeled as a function of radiation dose, chemotherapy, and host factors.
Results: Sarcomas occurred a median of 11.8 years (range, 5.3-31.3 years) from original diagnosis. Any exposure to radiation was associated with increased risk of secondary sarcoma (OR = 4.1, 95% CI = 1.8-9.5). A dose-response relation was observed, with elevated risks at doses between 10 and 29.9 Gy (OR = 15.6, 95% CI = 4.5-53.9), 30-49.9 Gy (OR = 16.0, 95% CI 3.8-67.8) and >50 Gy (OR = 114.1, 95% CI 13.5-964.8). Anthracycline exposure was associated with sarcoma risk (OR = 3.5, 95% CI = 1.6-7.7) adjusting for radiation dose, other chemotherapy, and primary cancer. Adjusting for treatment, survivors with a first diagnosis of Hodgkin lymphoma (OR = 10.7, 95% CI = 3.1-37.4) or primary sarcoma (OR = 8.4, 95% CI = 3.2-22.3) were more likely to develop a sarcoma.
Conclusions: Of the risk factors evaluated, radiation exposure was the most important for secondary sarcoma development in childhood cancer survivors; anthracycline chemotherapy exposure was also associated with increased risk. (C) 2012 Elsevier Inc.
C1 [Henderson, Tara O.] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA.
[Rajaraman, Preetha; Inskip, Peter D.] NCI, Bethesda, MD 20892 USA.
[Stovall, Marilyn; Smith, Susan A.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Constine, Louis S.] Univ Rochester, Rochester, NY USA.
[Olive, Aliza] Drexel Univ, Philadelphia, PA 19104 USA.
[Mertens, Ann] Emory Univ, Atlanta, GA 30322 USA.
[Meadows, Anna] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Neglia, Joseph P.] Univ Minnesota, Minneapolis, MN USA.
[Hammond, Sue] Nationwide Childrens Hosp, Columbus, OH USA.
[Whitton, John] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Robison, Leslie L.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
[Diller, Lisa] Childrens Hosp, Dana Farber Canc Inst, Ctr Canc, Boston, MA 02115 USA.
RP Henderson, TO (reprint author), Univ Chicago, Dept Pediat, 5841 S Maryland Ave,MC 4060, Chicago, IL 60637 USA.
EM thenderson@peds.bsd.uchicago.edu
FU National Cancer Institute (NCI) [U24 CA55727, K07CA134935]; NIH;
American Lebanese-Syrian Associated Charities
FX The Childhood Cancer Survivor Study is a collaborative,
multi-institutional study funded by the National Cancer Institute (NCI,
grant # U24 CA55727; L. L. Robison, Principal Investigator). Additional
support was provided by the Intramural Research Program of the NIH and
NCI, and the American Lebanese-Syrian Associated Charities. The primary
investigator, Dr. Henderson, received support from the NCI (grant
#K07CA134935, Health Beliefs and Behaviors: Cohort Studies in Childhood
Cancer Survivors).
NR 20
TC 36
Z9 36
U1 1
U2 9
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 2012
VL 84
IS 1
BP 224
EP 230
DI 10.1016/j.ijrobp.2011.11.022
PG 7
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 996CO
UT WOS:000308061900059
PM 22795729
ER
PT J
AU Allison, S
Bauermeister, JA
Bull, S
Lightfoot, M
Mustanski, B
Shegog, R
Levine, D
AF Allison, Susannah
Bauermeister, Jose A.
Bull, Sheana
Lightfoot, Marguerita
Mustanski, Brian
Shegog, Ross
Levine, Deb
TI The Intersection of Youth, Technology, and New Media with Sexual Health:
Moving the Research Agenda Forward
SO JOURNAL OF ADOLESCENT HEALTH
LA English
DT Editorial Material
DE Sexuality; Reproductive health; Adolescents; Young adults; Social
networking sites; Short message service
ID BEHAVIOR-CHANGE; TRANSMITTED-DISEASES; RISK ENVIRONMENT; YOUNG-PEOPLE;
MOBILE PHONE; INTERNET; INTERVENTIONS; PREVENTION; ONLINE; HIV
AB Youth bear a significant proportion of the sexually transmitted infection (STI)/HIV burden in the United States, CDC, 2010. Available at: http://www.cdc.gov/std/stats09/default.htm, with rates of some STIs increasing among youth of color and young men who have sex with men. Technology use among youth also continues to increase. The ubiquitous nature of technology use among youth offers a multitude of opportunities to promote youth sexual health and to prevent disease transmission and unplanned pregnancies. To date, there have been a handful of peer-reviewed articles published regarding the feasibility, acceptability, and effectiveness of using new media and technology for sexual health promotion. Despite recent publications, there is still a real need for high-quality research to understand the impact of different forms of new media use on youth sexual health, as well as to determine the best ways to harness technology to promote safer sex behaviors, both for the short- and long-term. In March 2011, Internet Sexuality Information Services (ISIS), National Institute of Mental Health (NIMH), and the Ford Foundation convened a meeting of scientists and technology experts to discuss how to effectively conduct sexual health promotion research using new forms of technology. The meeting was structured to cover the following topic areas: (i) research-community partnerships, (ii) institutional review board and ethical issues, (iii) theoretical frameworks, (iv) intervention approaches, (v) recruitment methods, and (vi) assessing impact. Presentations included case studies of successful technology-based HIV/STI prevention interventions for youth, which led to broader discussions on how to conduct research in this area. This article summarizes the meeting proceedings, highlights key points, offers recommendations, and outlines future directions. (c) 2012 Published by Elsevier Inc. on behalf of Society for Adolescent Health and Medicine.
C1 [Allison, Susannah] NIMH, NIH, Bethesda, MD 20892 USA.
[Bauermeister, Jose A.] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA.
[Bull, Sheana] Colorado Sch Publ Hlth, Aurora, CO USA.
[Lightfoot, Marguerita] Univ Calif San Francisco, Sch Med, San Francisco, CA USA.
[Mustanski, Brian] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Shegog, Ross] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA.
[Levine, Deb] Internet Sexual Informat Serv Inc, Oakland, CA USA.
RP Allison, S (reprint author), NIMH, NIH, Bethesda, MD 20892 USA.
OI Bauermeister, Jose/0000-0002-9276-2306
FU NIMH NIH HHS [K01 MH087242]
NR 47
TC 34
Z9 34
U1 0
U2 61
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1054-139X
J9 J ADOLESCENT HEALTH
JI J. Adolesc. Health
PD SEP
PY 2012
VL 51
IS 3
BP 207
EP 212
DI 10.1016/j.jadohealth.2012.06.012
PG 6
WC Psychology, Developmental; Public, Environmental & Occupational Health;
Pediatrics
SC Psychology; Public, Environmental & Occupational Health; Pediatrics
GA 994QJ
UT WOS:000307945900003
PM 22921129
ER
PT J
AU Keegan, THM
Lichtensztajn, DY
Kato, I
Kent, EE
Wu, XC
West, MM
Hamilton, AS
Zebrack, B
Bellizzi, KM
Smith, AW
AF Keegan, Theresa H. M.
Lichtensztajn, Daphne Y.
Kato, Ikuko
Kent, Erin E.
Wu, Xiao-Cheng
West, Michelle M.
Hamilton, Ann S.
Zebrack, Brad
Bellizzi, Keith M.
Smith, Ashley W.
CA AYA HOPE Study Collaborative Grp
TI Unmet adolescent and young adult cancer survivors information and
service needs: a population-based cancer registry study
SO JOURNAL OF CANCER SURVIVORSHIP-RESEARCH AND PRACTICE
LA English
DT Article
DE Adolescent; Young adult; Cancer survivor; Information needs; Service
needs
ID BREAST-CANCER; HEALTH SURVEY; DISPARITIES; OUTCOMES; WOMEN; CARE
AB We described unmet information and service needs of adolescent and young adult (AYA) cancer survivors (15-39 years of age) and identified sociodemographic and health-related factors associated with these unmet needs.
We studied 523 AYAs recruited from seven population-based cancer registries, diagnosed with acute lymphocytic leukemia, Hodgkin's lymphoma, non-Hodgkin's lymphoma, germ cell cancer, or sarcoma in 2007-2008. Participants completed surveys a median of 11 months from diagnosis. Multivariable logistic regression analyses were used to estimate associations between unmet (information and service) needs and sociodemographic and health-related factors.
More than half of AYAs had unmet information needs relating to their cancer returning and cancer treatments. AYAs needing services, but not receiving them, ranged from 29 % for in-home nursing to 75 % for a support group. The majority of AYAs who needed a pain management expert, physical/occupational therapist, mental health worker, or financial advice on paying for health care did not receive services. In multivariable analyses, older participants, men, participants of non-white race/ethnicity, and participants who reported less than excellent general health or fair/poor quality of care were more likely to report unmet information needs. Factors associated with both unmet service and information needs included physical health or emotional problems interfering with social activities or having a parts per thousand yen3 physical treatment-related symptoms.
Recently diagnosed AYA cancer survivors have substantial unmet information needs varying by demographic and health-related factors.
We identified subgroups of AYA cancer survivors with high unmet needs that can be targeted for interventions and referrals.
C1 [Keegan, Theresa H. M.; Lichtensztajn, Daphne Y.] Canc Prevent Inst Calif, Fremont, CA 94538 USA.
[Keegan, Theresa H. M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Kato, Ikuko] Wayne State Univ, Dept Pathol & Oncol, Detroit, MI USA.
[Kent, Erin E.] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
[Wu, Xiao-Cheng] Louisiana State Univ, Program Epidemiol, Sch Publ Hlth, Hlth Sci Ctr, New Orleans, LA USA.
[West, Michelle M.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA.
[Hamilton, Ann S.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Zebrack, Brad] Univ Michigan, Sch Social Work, Ann Arbor, MI 48109 USA.
[Bellizzi, Keith M.] Univ Connecticut, Dept Human Dev & Family Studies, Mansfield, PA USA.
[Smith, Ashley W.] NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci,NIH, Bethesda, MD 20892 USA.
RP Keegan, THM (reprint author), Canc Prevent Inst Calif, 2201 Walnut Ave,Suite 300, Fremont, CA 94538 USA.
EM theresa.keegan@CPIC.org
FU [N01-PC-54402]; [N01-PC-54404]; [N01-PC-35136]; [N01-PC-35139];
[N01-PC-35142]; [N01-PC-35143]; [N01-PC-35145]
FX This study is supported by contract numbers N01-PC-54402, N01-PC-54404,
N01-PC-35136, N01-PC-35139, N01-PC-35142, N01-PC-35143, and
N01-PC-35145.
NR 30
TC 67
Z9 67
U1 6
U2 59
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 2012
VL 6
IS 3
BP 239
EP 250
DI 10.1007/s11764-012-0219-9
PG 12
WC Oncology; Social Sciences, Biomedical
SC Oncology; Biomedical Social Sciences
GA 999PB
UT WOS:000308325200001
PM 22457219
ER
PT J
AU Gaba, A
Grivennikov, SI
Do, MV
Stumpo, DJ
Blackshear, PJ
Karin, M
AF Gaba, Anthony
Grivennikov, Sergei I.
Do, Mahn Vu
Stumpo, Deborah J.
Blackshear, Perry J.
Karin, Michael
TI Cutting Edge: IL-10-Mediated Tristetraprolin Induction Is Part of a
Feedback Loop That Controls Macrophage STAT3 Activation and Cytokine
Production
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID TNF-ALPHA PRODUCTION; NF-KAPPA-B; INFLAMMATORY RESPONSE; MURINE
MACROPHAGES; MESSENGER-RNAS; GROWTH-FACTOR; IL-10; INTERLEUKIN-10;
INHIBITION; MICE
AB In activated macrophages, the anti-inflammatory cytokine IL-10 inhibits expression of molecules that propagate inflammation in a manner that depends on transcription factor STAT3. Expression of IL-10 is regulated posttranscriptionally by the RNA-binding protein tristetraprolin (TTP), which destabilizes IL-10 mRNA in activated macrophages. Using LPS-activated bone marrow-derived murine macrophages, we demonstrate that TTP is a negative regulator of the IL-10/STAT3 anti-inflammatory response. LPS-stimulated TTP-deficient macrophages overproduced IL-10, contained increased amounts of activated STAT3, and showed reduced expression of inflammatory cytokines, including cytokines encoded by TTP target mRNAs. Thus, in LPS-stimulated TTP-deficient macrophages, increased IL-10/STAT3 anti-inflammatory control was dominant over the mRNA stabilization of specific TTP targets. The TTP gene promoter contains a conserved STAT3 binding site, and IL-10 induces STAT3 recruitment to this site. Correspondingly, STAT3 was required for efficient IL-10-induced TTP expression. Hence, by inducing TTP expression, STAT3 activates a negative regulatory loop that controls the IL-10/STAT3 anti-inflammatory response. The Journal of Immunology, 2012, 189: 2089-2093.
C1 [Gaba, Anthony; Grivennikov, Sergei I.; Do, Mahn Vu; Karin, Michael] Univ Calif San Diego, Sch Med, Dept Pharmacol, Lab Gene Regulat & Signal Transduct, La Jolla, CA 92093 USA.
[Stumpo, Deborah J.; Blackshear, Perry J.] NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA.
RP Karin, M (reprint author), Univ Calif San Diego, Sch Med, Dept Pharmacol, Lab Gene Regulat & Signal Transduct, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM karinoffice@ucsd.edu
FU National Cancer Institute; National Institutes of Health Research
Supplement [CA118165]; Crohn's and Colitis Foundation of America [CDA
2693]; National Institutes of Health [K99-DK088589]; University of
California San Diego Digestive Diseases Research Development Center
pilot grant [DK080506]
FX This work was supported by National Institutes of Health grants to M.
K., who is an American Cancer Society Research Professor. A.G. was
supported by a National Cancer Institute-sponsored Cancer Therapeutic
Training Program and National Institutes of Health Research Supplement
to Promote Diversity in Health-Related Research (CA118165). S.I.G. was
supported by the Crohn's and Colitis Foundation of America (CDA 2693), a
Pathway to Independence award from the National Institutes of Health
(K99-DK088589), and a University of California San Diego Digestive
Diseases Research Development Center pilot grant (DK080506).
NR 30
TC 21
Z9 21
U1 0
U2 6
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD SEP 1
PY 2012
VL 189
IS 5
BP 2089
EP 2093
DI 10.4049/jimmunol.1201126
PG 5
WC Immunology
SC Immunology
GA 996JZ
UT WOS:000308083600005
PM 22865915
ER
PT J
AU Mkrtichyan, M
Najjar, YG
Raulfs, EC
Liu, LD
Langerman, S
Guittard, G
Ozbun, L
Khleif, SN
AF Mkrtichyan, Mikayel
Najjar, Yana G.
Raulfs, Estella C.
Liu, Linda
Langerman, Solomon
Guittard, Geoffrey
Ozbun, Laurent
Khleif, Samir N.
TI B7-DC-Ig Enhances Vaccine Effect by a Novel Mechanism Dependent on PD-1
Expression Level on T Cell Subsets
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID TUMOR-INFILTRATING LYMPHOCYTES; REGULATORY T; INCREASED POPULATIONS;
PERIPHERAL-BLOOD; CLINICAL-SIGNIFICANCE; CARCINOMA PATIENTS;
PANCREATIC-CANCER; IMMUNE-RESPONSE; B7-H1; CYCLOPHOSPHAMIDE
AB Programmed death receptor 1 (PD-1) is an important signaling molecule often involved in tumor-mediated suppression of activated immune cells. Binding of this receptor to its ligands, B7-H1 (PD-L1) and B7-DC (PD-L2), attenuates T cell activation, reduces IL-2 and IFN-gamma secretion, decreases proliferation and cytotoxicity, and induces apoptosis. B7-DC-Ig is a recombinant protein that binds and targets PD-1. It is composed of an extracellular domain of murine B7-DC fused to the Fc portion of murine IgG2a. In this study, we demonstrate that B7-DC-Ig can enhance the therapeutic efficacy of vaccine when combined with cyclophosphamide. We show that this combination significantly enhances Ag-specific immune responses and leads to complete eradication of established tumors in 60% of mice and that this effect is CD8 dependent. We identified a novel mechanism by which B7-DC-Ig exerts its therapeutic effect that is distinctly different from direct blocking of the PD-L1-PD-1 interaction. In this study, we demonstrate that there are significant differences between levels and timing of surface PD-1 expression on different T cell subsets. We found that these differences play critical roles in anti-tumor immune effect exhibited by B7-DC-Ig through inhibiting proliferation of PD-1(high) CD4 T cells, leading to a significant decrease in the level of these cells, which are enriched for regulatory T cells, within the tumor. In addition, it also leads to a decrease in PD-1(high) CD8 T cells, tipping the balance toward nonexhausted functional PD-1(low) CD8 T cells. We believe that the PD-1 expression level on T cells is a crucial factor that needs to be considered when designing PD-1-targeting immune therapies. The Journal of Immunology, 2012, 189: 2338-2347.
C1 [Mkrtichyan, Mikayel; Najjar, Yana G.; Raulfs, Estella C.; Guittard, Geoffrey; Ozbun, Laurent; Khleif, Samir N.] NCI, Canc Vaccine Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Liu, Linda; Langerman, Solomon] Amplimmune Inc, Gaithersburg, MD 20878 USA.
RP Khleif, SN (reprint author), Georgia Hlth Sci Univ, Ctr Canc, 1410 Laney Walker Blvd,CN-2133, Augusta, GA 30912 USA.
EM skhleif@georgiahealth.edu
OI Guittard, Geoffrey/0000-0002-6061-8553
FU Intramural Research Program of the 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 43
TC 25
Z9 26
U1 2
U2 6
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD SEP 1
PY 2012
VL 189
IS 5
BP 2338
EP 2347
DI 10.4049/jimmunol.1103085
PG 10
WC Immunology
SC Immunology
GA 996JZ
UT WOS:000308083600033
PM 22837483
ER
PT J
AU Li, HJ
Ye, CT
Ji, GL
Wu, XH
Xiang, Z
Li, YY
Cao, YH
Liu, XL
Douek, DC
Price, DA
Han, JH
AF Li, Hanjie
Ye, Congting
Ji, Guoli
Wu, Xiaohui
Xiang, Zhe
Li, Yuanyue
Cao, Yonghao
Liu, Xiaolong
Douek, Daniel C.
Price, David A.
Han, Jiahuai
TI Recombinatorial Biases and Convergent Recombination Determine
Interindividual TCR beta Sharing in Murine Thymocytes
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID T-CELL REPERTOIRE; V(D)J RECOMBINATION; POSITIVE SELECTION; RECEPTOR
BIAS; DIVERSITY; RESPONSES; IMMUNITY; USAGE; CDR3
AB Overlap of TCR repertoires among individuals provides the molecular basis for public T cell responses. By deep-sequencing the TCR beta repertoires of CD4(+)CD8(+) thymocytes from three individual mice, we observed that a substantial degree of TCR beta overlap, comprising similar to 10-15% of all unique amino acid sequences and similar to 5-10% of all unique nucleotide sequences across any two individuals, is already present at this early stage of T cell development. The majority of TCR beta sharing between individual thymocyte repertoires could be attributed to the process of convergent recombination, with additional contributions likely arising from recombinatorial biases; the role of selection during intrathymic development was negligible. These results indicate that the process of TCR gene recombination is the major determinant of clonotype sharing between individuals. The Journal of Immunology, 2012, 189: 2404-2413.
C1 [Li, Hanjie; Li, Yuanyue; Han, Jiahuai] Xiamen Univ, State Key Lab Cellular Stress Biol, Xiamen 361005, Fujian, Peoples R China.
[Li, Hanjie; Li, Yuanyue; Han, Jiahuai] Xiamen Univ, Sch Life Sci, Xiamen 361005, Fujian, Peoples R China.
[Ye, Congting; Ji, Guoli; Wu, Xiaohui; Xiang, Zhe] Xiamen Univ, Dept Automat, Xiamen 361005, Fujian, Peoples R China.
[Cao, Yonghao; Liu, Xiaolong] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Mol Cell Biol Lab, Shanghai 200031, Peoples R China.
[Douek, Daniel C.; Price, David A.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Price, David A.] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff CF14 4XN, S Glam, Wales.
RP Han, JH (reprint author), Xiamen Univ, State Key Lab Cellular Stress Biol, Xiamen 361005, Fujian, Peoples R China.
EM glji@xmu.edu.cn; dprice1@mail.nih.gov; jhan@xmu.edu.cn
RI Han, J/G-4671-2010; Ji, GL/G-3355-2010; Cao, Yonghao/I-5194-2013; Price,
David/C-7876-2013;
OI Price, David/0000-0001-9416-2737; Li, Yuanyue/0000-0001-5971-0355
FU 973 Program [2009CB522200]; Natural Science Foundation of China
[30830092, 30921005, 91029304, 81061160512, 61174161]; Specialized
Research Fund for the Doctoral Program of Higher Education of China
[20090121110022]; Fundamental Research Funds for the Central
Universities of Xiamen University [2011121047, 201112G018, CXB2011035]
FX This work was supported by the 973 Program (2009CB522200), Natural
Science Foundation of China Grants 30830092, 30921005, 91029304,
81061160512, and 61174161, the Specialized Research Fund for the
Doctoral Program of Higher Education of China (No. 20090121110022), and
the Fundamental Research Funds for the Central Universities of Xiamen
University (Nos. 2011121047, 201112G018, and CXB2011035).
NR 28
TC 17
Z9 18
U1 1
U2 12
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD SEP 1
PY 2012
VL 189
IS 5
BP 2404
EP 2413
DI 10.4049/jimmunol.1102087
PG 10
WC Immunology
SC Immunology
GA 996JZ
UT WOS:000308083600040
PM 22826324
ER
PT J
AU Sun, DW
Raisley, B
Langer, M
Iyer, JK
Vedham, V
Ballard, JL
James, JA
Metcalf, J
Coggeshall, KM
AF Sun, Dawei
Raisley, Brent
Langer, Marybeth
Iyer, Janaki K.
Vedham, Vidya
Ballard, Jimmy L.
James, Judith A.
Metcalf, Jordan
Coggeshall, K. Mark
TI Anti-Peptidoglycan Antibodies and Fc gamma Receptors Are the Key
Mediators of Inflammation in Gram-Positive Sepsis
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID BLOOD-STREAM INFECTIONS; MULTIPLE ORGAN FAILURE; NECROSIS-FACTOR-ALPHA;
CELL-WALL COMPONENTS; STAPHYLOCOCCUS-AUREUS; BACTERIAL PEPTIDOGLYCAN;
LIPOTEICHOIC ACID; HOST RECOGNITION; UNITED-STATES; NOD2
AB Gram-positive bacteria are an important public health problem, but it is unclear how they cause systemic inflammation in sepsis. Our previous work showed that peptidoglycan (PGN) induced proinflammatory cytokines in human cells by binding to an unknown extracellular receptor, followed by phagocytosis leading to the generation of NOD ligands. In this study, we used flow cytometry to identify host factors that supported PGN binding to immune cells. PGN binding required plasma, and plasma from all tested healthy donors contained IgG recognizing PGN. Plasma depleted of IgG or of anti-PGN Abs did not support PGN binding or PGN-triggered cytokine production. Adding back intact but not F(ab')(2) IgG restored binding and cytokine production. Transfection of HEK293 cells with Fc gamma RIIA enabled PGN binding and phagocytosis. These data establish a key role for anti-PGN IgG and Fc gamma Rs in supporting inflammation to a major structural element of Gram-positive bacteria and suggest that anti-PGN IgG contributes to human pathology in Gram-positive sepsis. The Journal of Immunology, 2012, 189: 2423-2431.
C1 [Sun, Dawei; Raisley, Brent; Iyer, Janaki K.; Coggeshall, K. Mark] Oklahoma Med Res Fdn, Immunobiol & Canc Program, Oklahoma City, OK 73104 USA.
[Sun, Dawei; Coggeshall, K. Mark] Univ Oklahoma, Dept Cell Biol, Oklahoma City, OK 73104 USA.
[Langer, Marybeth; Metcalf, Jordan] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Pulm & Crit Care Div, Oklahoma City, OK 73104 USA.
[Vedham, Vidya] NCI, Methods & Technol Branch, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Ballard, Jimmy L.] Univ Oklahoma, Dept Microbiol, Oklahoma City, OK 73104 USA.
[James, Judith A.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Program, Oklahoma City, OK 73104 USA.
RP Coggeshall, KM (reprint author), Oklahoma Med Res Fdn, Immunobiol & Canc Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.
EM mark-coggeshall@omrf.org
FU National Institutes of Health [2 U19 AI062629]
FX This work was supported by National Institutes of Health Grant 2 U19
AI062629.
NR 46
TC 10
Z9 11
U1 2
U2 9
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 2012
VL 189
IS 5
BP 2423
EP 2431
DI 10.4049/jimmunol.1201302
PG 9
WC Immunology
SC Immunology
GA 996JZ
UT WOS:000308083600042
PM 22815288
ER
PT J
AU Liu, WL
Yan, M
Liu, YQ
McLeish, KR
Coleman, WG
Rodgers, GP
AF Liu, Wenli
Yan, Ming
Liu, Yueqin
McLeish, Kenneth R.
Coleman, William G., Jr.
Rodgers, Griffin P.
TI Olfactomedin 4 Inhibits Cathepsin C-Mediated Protease Activities,
Thereby Modulating Neutrophil Killing of Staphylococcus aureus and
Escherichia coli in Mice
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID SERINE PROTEASES; HELICOBACTER-PYLORI; INNATE IMMUNITY; CELL-GROWTH;
HGC-1; DIFFERENTIATION; EXPRESSION; GRANULES; GW112; GENE
AB Neutrophils kill bacteria generally through oxidative and nonoxidative mechanisms. Whereas much research has focused on the enzymes essential for neutrophil killing, little is known about the regulatory molecules responsible for such killing. In this study, we investigated the role of olfactomedin 4 (OLFM4), an olfactomedin-related glycoprotein, in neutrophil bactericidal capability and host innate immunity. Neutrophils from OLFM4(-/-) mice have increased intracellular killing of Staphylococcus aureus and Escherichia coli in vitro. The OLFM4(-/-) mice have enhanced in vivo bacterial clearance and are more resistant to sepsis when challenged with S. aureus or E. coli by i.p. injection. OLFM4 was found to interact with cathepsin C, a cysteine protease that plays an important role in bacterial killing and immune regulation. We demonstrated that OLFM4 inhibited cathepsin C activity in vitro and in vivo. The cathepsin C activity in neutrophils from OLFM4(-/-) mice was significantly higher than that in neutrophils from wild-type littermate mice. The activities of three serine proteases (neutrophil elastase, cathepsin G, and proteinase 3), which require cathepsin C activity for processing and maturity, were also significantly higher in OLFM4(-/-) neutrophils. The bacterial killing and clearance capabilities observed in OLFM4(-/-) mice that were enhanced relative to wild-type mice were significantly compromised by the additional loss of cathepsin C in mice with OLFM4 and cathepsin C double deficiency. These results indicate that OLFM4 is an important negative regulator of neutrophil bactericidal activity by restricting cathepsin C activity and its downstream granule-associated serine proteases. The Journal of Immunology, 2012, 189: 2460-2467.
C1 [Rodgers, Griffin P.] NHLBI, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Yan, Ming; Coleman, William G., Jr.] NIDDKD, Lab Biochem & Genet, Bethesda, MD 20892 USA.
[Liu, Yueqin] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[McLeish, Kenneth R.] Univ Louisville, Dept Med, Louisville, KY 40202 USA.
RP Rodgers, GP (reprint author), NHLBI, Mol & Clin Hematol Branch, NIH, Bldg 10,Room 9N119,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM gr5n@nih.gov
RI McLeish, Kenneth/B-9819-2013
OI McLeish, Kenneth/0000-0002-7816-3286
FU National Institute of Diabetes and Digestive and Kidney Disease;
National Institute on Minority Health and Health Disparities, National
Institutes of Health [Y3-DK-3521-07]
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Disease and
Inter-Agency Agreement Y3-DK-3521-07 with the National Institute on
Minority Health and Health Disparities, National Institutes of Health.
NR 29
TC 21
Z9 22
U1 0
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 2012
VL 189
IS 5
BP 2460
EP 2467
DI 10.4049/jimmunol.1103179
PG 8
WC Immunology
SC Immunology
GA 996JZ
UT WOS:000308083600046
PM 22844115
ER
PT J
AU Verma, A
White, M
Vathipadiekal, V
Tripathi, S
Mbianda, J
Ieong, M
Qi, L
Taubenberger, JK
Takahashi, K
Jensenius, JC
Thiel, S
Hartshorn, KL
AF Verma, Anamika
White, Mitchell
Vathipadiekal, Vinod
Tripathi, Shweta
Mbianda, Julvet
Ieong, Micheal
Qi, Li
Taubenberger, Jeffery K.
Takahashi, Kazue
Jensenius, Jens C.
Thiel, Steffen
Hartshorn, Kevan L.
TI Human H-Ficolin Inhibits Replication of Seasonal and Pandemic Influenza
A Viruses
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID SURFACTANT PROTEIN-D; PATTERN-RECOGNITION MOLECULES; INNATE IMMUNE
PROTEINS; MANNAN-BINDING LECTIN; ANTIINFLUENZA ACTIVITIES; COMPLEMENT
ACTIVATION; ANTIVIRAL ACTIVITY; PENTRAXIN PTX3; HAKATA ANTIGEN; ACETYL
GROUPS
AB The collectins have been shown to have a role in host defense against influenza A virus (IAV) and other significant viral pathogens (e. g., HIV). The ficolins are a related group of innate immune proteins that are present at relatively high concentrations in serum, but also in respiratory secretions; however, there has been little study of the role of ficolins in viral infection. In this study, we demonstrate that purified recombinant human H-ficolin and H-ficolin in human serum and bronchoalveolar lavage fluid bind to IAV and inhibit viral infectivity and hemagglutination activity in vitro. Removal of ficolins from human serum or bronchoalveolar lavage fluid reduces their antiviral activity. Inhibition of IAV did not involve the calcium-dependent lectin activity of H-ficolin. We demonstrate that H-ficolin is sialylated and that removal of sialic acid abrogates IAV inhibition, while addition of the neuraminidase inhibitor oseltamivir potentiates neutralization, hemagglutinin inhibition, and viral aggregation caused by H-ficolin. Pandemic and mouse-adapted strains of IAV are generally not inhibited by the collectins surfactant protein D or mannose binding lectin because of a paucity of glycan attachments on the hemagglutinin of these strains. In contrast, H-ficolin inhibited both the mouse-adapted PR-8 H1N1 strain and a pandemic H1N1 strain from 2009. H-ficolin also fixed complement to a surface coated with IAV. These findings suggest that H-ficolin contributes to host defense against IAV. The Journal of Immunology, 2012, 189: 2478-2487.
C1 [Verma, Anamika; White, Mitchell; Tripathi, Shweta; Mbianda, Julvet; Ieong, Micheal; Hartshorn, Kevan L.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Vathipadiekal, Vinod] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA.
[Qi, Li; Taubenberger, Jeffery K.] NIAID, Bethesda, MD 20892 USA.
[Takahashi, Kazue] Massachusetts Gen Hosp, Dept Pediat, Program Dev Immunol, Boston, MA 02114 USA.
[Jensenius, Jens C.; Thiel, Steffen] Aarhus Univ, Dept Biomed, DK-8000 Aarhus, Denmark.
RP Hartshorn, KL (reprint author), Boston Univ, Sch Med, Dept Med, Room 414,650 Albany St, Boston, MA 02118 USA.
EM khartsho@bu.edu
OI Hartshorn, Kevan/0000-0002-7196-7433; Vathipadiekal,
Vinod/0000-0002-8181-6890
FU National Institutes of Health [AI-83222, HL069031]; National Institutes
of Health; Novo Nordisk Foundation
FX This work was supported by National Institutes of Health Grants AI-83222
and HL069031 (to K. L. H.), National Institutes of Health intramural
funds (to J.K.T.), and the Novo Nordisk Foundation (to S. Thiel).
NR 39
TC 29
Z9 30
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 2012
VL 189
IS 5
BP 2478
EP 2487
DI 10.4049/jimmunol.1103786
PG 10
WC Immunology
SC Immunology
GA 996JZ
UT WOS:000308083600048
PM 22851708
ER
PT J
AU Duley, AK
Ploquin, MJY
Eksmond, U
Ammann, CG
Messer, RJ
Myers, L
Hasenkrug, KJ
Kassiotis, G
AF Duley, Amanda K.
Ploquin, Mickael J. -Y.
Eksmond, Urszula
Ammann, Christoph G.
Messer, Ronald J.
Myers, Lara
Hasenkrug, Kim J.
Kassiotis, George
TI Negative Impact of IFN-gamma on Early Host Immune Responses to
Retroviral Infection
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CD8(+) T-CELLS; DEHYDROGENASE-ELEVATING VIRUS; MURINE-LEUKEMIA-VIRUS;
INTERFERON-GAMMA; FRIEND-VIRUS; LYMPHOCYTE-ACTIVATION;
MONOCLONAL-ANTIBODIES; ENVELOPE PROTEIN; IN-VIVO; MICE
AB The immune system is tasked with defending against a myriad of microbial infections, and its response to a given infectious microbe may be strongly influenced by coinfection with another microbe. It was shown that infection of mice with lactate dehydrogenase-elevating virus (LDV) impairs early adaptive immune responses to Friend virus (FV) coinfection. To investigate the mechanism of this impairment, we examined LDV-induced innate immune responses and found LDV-specific induction of IFN-alpha and IFN-gamma. LDV-induced IFN-alpha had little effect on FV infection or immune responses, but unexpectedly, LDV-induced IFN-gamma production dampened Th1 adaptive immune responses and enhanced FV infection. Two distinct effects were identified. First, LDV-induced IFN-gamma signaling indirectly modulated FV-specific CD8(+) T cell responses. Second, intrinsic IFN-gamma signaling in B cells promoted polyclonal B cell activation and enhanced early FV infection, despite promotion of germinal center formation and neutralizing Ab production. Results from this model reveal that IFN-gamma production can have detrimental effects on early adaptive immune responses and virus control. The Journal of Immunology, 2012, 189: 2521-2529.
C1 [Duley, Amanda K.; Ammann, Christoph G.; Messer, Ronald J.; Myers, Lara; Hasenkrug, Kim J.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Ploquin, Mickael J. -Y.; Eksmond, Urszula; Kassiotis, George] Natl Inst Med Res, Med Res Council, Div Immunoregulat, London NW7 1AA, England.
RP Hasenkrug, KJ (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA.
EM khasenkrug@nih.gov; gkassio@nimr.mrc.ac.uk
OI Ammann, Christoph/0000-0002-6267-1286
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health; U.K. Medical Research Council [U117581330]
FX This work was supported by the Intramural Program of the National
Institute of Allergy and Infectious Diseases, National Institutes of
Health and by the U.K. Medical Research Council (U117581330).
NR 49
TC 7
Z9 7
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 2012
VL 189
IS 5
BP 2521
EP 2529
DI 10.4049/jimmunol.1201125
PG 9
WC Immunology
SC Immunology
GA 996JZ
UT WOS:000308083600052
PM 22821964
ER
PT J
AU Schellmann, N
Panjideh, H
Fasold, P
Bachran, D
Bachran, C
Deckert, PM
Fuchs, H
AF Schellmann, Nicole
Panjideh, Hossein
Fasold, Patricia
Bachran, Diana
Bachran, Christopher
Deckert, Peter M.
Fuchs, Hendrik
TI Targeted Tumor Therapy With a Fusion Protein of an Antiangiogenic Human
Recombinant scFv and Yeast Cytosine Deaminase
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE ADEPT; ED-B; L19; prodrug; targeted tumor therapy
ID ED-B DOMAIN; HUMAN-ANTIBODY FRAGMENT; ENZYME-PRODRUG THERAPY;
SINGLE-CHAIN ANTIBODY; PICHIA-PASTORIS; MONOCLONAL-ANTIBODIES;
CANCER-THERAPY; ANGIOGENESIS; FIBRONECTIN; EXPRESSION
AB In adults, endothelial cell division occurs only in wound healing, during menstruation, or in diseases such as wet age-related macular degeneration or development of benign or malignant tissues. Angiogenesis is one of the major requirements to supply the fast developing tumor tissue with oxygen and nutrients, and enables it to spread into other tissues far from its origin. We selected the extradomain B (ED-B), a splice variant of fibronectin, which is exclusively expressed in ovaries, uterus, during wound healing, and in tumor tissues, as a target for the development of an innovative antiangiogenic, prodrug-based targeted tumor therapy approach. We designed a fusion protein termed L19CDy-His, consisting of the antibody single chain fragment L19 for targeting ED-B and yeast cytosine deaminase for the conversion of 5-fluorocytosine into cytotoxic 5-fluorouracil. We purified high amounts of the fusion protein from Pichia pastoris that is stable, enzymatically active, and retains 75% of its activity after incubation with human plasma for up to 72 hours. The binding of L19CDy-His to ED-B was confirmed by an enzyme-linked immunosorbent assay and quantified by surface plasmon resonance spectroscopy determining a KD value of 81 +/- 7 nM. L19CDy-His successfully decreased cell survival of the murine ED-B-expressing teratocarcinoma cell line F9 upon addition of the prodrug 5-fluorocytosine. Our data demonstrate the suitability of targeting ED-B by L19CDy-His for effective prodrug-based tumor therapy.
C1 [Schellmann, Nicole; Fasold, Patricia; Bachran, Diana; Bachran, Christopher; Fuchs, Hendrik] Charite, Inst Labs Med Klin Chem & Pathobiochem, D-12200 Berlin, Germany.
[Panjideh, Hossein] Max Delbruck Ctr Mol Med MDC, Dept Mol Tumor Genet & Immunogenet, Berlin, Germany.
[Fasold, Patricia] InVivo BioTech Serv GmbH, Hennigsdorf, Germany.
[Deckert, Peter M.] Stadt Klinikum Brandenburg GmbH, Innere Med Gastroenterologie Onkol 2, Brandenburg, Germany.
[Bachran, Christopher] NIAID, NIH, Bethesda, MD 20892 USA.
RP Fuchs, H (reprint author), Charite, Inst Labs Med Klin Chem & Pathobiochem, Campus Benjamin Franklin,Hindenburgdamm 30, D-12200 Berlin, Germany.
EM hendrik.fuchs@charite.de
FU Deutsche Krebshilfe [108492]; Kommission fur wissenschaftliche
Nachwuchsforderung und Weiterbildung, Charite-Universitats-medizin
Berlin
FX Supported by grants from Deutsche Krebshilfe (108492) and the Kommission
fur wissenschaftliche Nachwuchsforderung und Weiterbildung,
Charite-Universitats-medizin Berlin.
NR 34
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD SEP
PY 2012
VL 35
IS 7
BP 570
EP 578
DI 10.1097/CJI.0b013e31826b1fb4
PG 9
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 997AG
UT WOS:000308135700005
PM 22892453
ER
PT J
AU Kellman, P
Arai, AE
AF Kellman, Peter
Arai, Andrew E.
TI Cardiac imaging techniques for physicians: Late enhancement
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Review
DE late enhancement; delayed enhancement; gadolinium; cardiac magnetic
resonance imaging; myocardial infarction; viability
ID CARDIOVASCULAR MAGNETIC-RESONANCE; SENSITIVE-INVERSION-RECOVERY; ACUTE
MYOCARDIAL-INFARCTION; RIGHT-VENTRICULAR CARDIOMYOPATHY; DELAYED
CONTRAST-ENHANCEMENT; STATE FREE PRECESSION; PERIINFARCT ZONE;
IRREVERSIBLE INJURY; PULSE SEQUENCE; BORDER ZONE
AB Late enhancement imaging is used to diagnose and characterize a wide range of ischemic and nonischemic cardiomyopathies, and its use has become ubiquitous in the cardiac MR exam. As the use of late enhancement imaging has matured and the span of applications has widened, the demands on image quality have grown. The characterization of subendocardial MI now includes the accurate quantification of scar size, shape, and characterization of borders which have been shown to have prognostic significance. More diverse patterns of late enhancement including patchy, mid-wall, subepicardial, or diffuse enhancement are of interest in diagnosing nonischemic cardiomyopathies. As clinicians are examining late enhancement images for more subtle indication of fibrosis, the demand for lower artifacts has increased. A range of new techniques have emerged to improve the speed and quality of late enhancement imaging including: methods for acquisition during free breathing, and fat water separated imaging for characterizing fibrofatty infiltration and reduction of artifacts related to the presence of fat. Methods for quantification of T1 and extracellular volume fraction are emerging to tackle the issue of discriminating globally diffuse fibrosis from normal healthy tissue which is challenging using conventional late enhancement methods. The aim of this review will be to describe the current state of the art and to provide a guide to various clinical protocols that are commonly used. J. Magn. Reson. Imaging 2012;36:529542. Published 2012 Wiley Periodicals, Inc.
C1 [Kellman, Peter; Arai, Andrew E.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Kellman, P (reprint author), NHLBI, NIH, 10 Ctr Dr,MSC 1061,Bldg 10,Room B1D416, Bethesda, MD 20892 USA.
EM kellman@nih.gov
FU NIH/NHLBI Intramural Research Program
FX Contract grant sponsor: NIH/NHLBI Intramural Research Program.
NR 73
TC 21
Z9 21
U1 0
U2 8
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 2012
VL 36
IS 3
BP 529
EP 542
DI 10.1002/jmri.23605
PG 14
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 994MM
UT WOS:000307934900002
PM 22903654
ER
PT J
AU Vogel-Claussen, J
Tomas, MS
Newatia, A
Boyce, D
Pinheiro, A
Abraham, R
Abraham, T
Bluemke, DA
AF Vogel-Claussen, Jens
Tomas, Miguel Santaularia
Newatia, Amit
Boyce, Danielle
Pinheiro, Aurelio
Abraham, Roselle
Abraham, Theodore
Bluemke, David A.
TI Cardiac MRI evaluation of hypertrophic cardiomyopathy: Left ventricular
outflow tract/aortic valve diameter ratio predicts severity of LVOT
obstruction
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE hypertrophic cardiomyopathy; left ventricular outflow tract; MRI
ID CARDIOVASCULAR MAGNETIC-RESONANCE; LATE GADOLINIUM ENHANCEMENT; TRACT
OBSTRUCTION; DIFFERENTIAL-DIAGNOSIS; DELAYED ENHANCEMENT; RISK
STRATIFICATION; FLOW PATTERNS; SUDDEN-DEATH; ECHOCARDIOGRAPHY;
APPEARANCES
AB Purpose: To evaluate if left ventricular outflow tract/aortic valve (LVOT/AO) diameter ratio measured by cardiac magnetic resonance (CMR) imaging is an accurate marker for LVOT obstruction in patients with hypertrophic cardiomyopathy (HCM) compared to Doppler echocardiography. Materials and Methods: In all, 92 patients with HCM were divided into three groups based on their resting echocardiographic LVOT pressure gradient (PG): <30 mmHg at rest (nonobstructive, n = 31), <30 mmHg at rest, >30 mmHg after provocation (latent, n = 29), and >30 mmHg at rest (obstructive, n = 32). The end-systolic dimension of the LVOT on 3-chamber steady-state free precession (SSFP) CMR was divided by the end diastolic aortic valve diameter to calculate the LVOT/AO diameter ratio. Results: There were significant differences in the LVOT/AO diameter ratio among the three subgroups (nonobstructive 0.60 +/- 0.13, latent 0.41 +/- 0.16, obstructive 0.24 +/- 0.09, P < 0.001). There was a strong linear inverse correlation between the LVOT/AO diameter ratio and the log of the LVOT pressure gradient (r = -0.84, P < 0.001). For detection of a resting gradient >30 mmHg, the LVOT/AO diameter ratio the area under the receiver operating characteristic (ROC) curve was 0.91 (95% confidence interval [CI] 0.850.97). For detection of a resting and/or provoked gradient >30 mmHg, the LVOT/AO diameter ratio area under the ROC curve was 0.90 (95% CI 0.840.96). Conclusion: The LVOT/AO diameter ratio is an accurate, reproducible, noninvasive, and easy to use CMR marker to assess LVOT pressure gradients in patients with HCM. J. Magn. Reson. Imaging 2012;36:598603. (C) 2012 Wiley Periodicals, Inc.
C1 [Vogel-Claussen, Jens] Hannover Med Sch, Dept Radiol, D-30625 Hannover, Germany.
[Vogel-Claussen, Jens; Newatia, Amit] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA.
[Tomas, Miguel Santaularia; Pinheiro, Aurelio; Abraham, Roselle; Abraham, Theodore] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA.
[Boyce, Danielle] Johns Hopkins Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21205 USA.
[Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, NIH, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA.
RP Vogel-Claussen, J (reprint author), Hannover Med Sch, Dept Radiol, Carl Neuberg Str 1, D-30625 Hannover, Germany.
EM vogel-claussen.jens@mh-hannover.de
OI Bluemke, David/0000-0002-8323-8086
FU National Institutes of Health (NIH) [HL 098046]
FX Contract grant sponsor: National Institutes of Health (NIH); Contract
grant number: HL 098046.
NR 34
TC 1
Z9 2
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 2012
VL 36
IS 3
BP 598
EP 603
DI 10.1002/jmri.23677
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 994MM
UT WOS:000307934900008
PM 22549972
ER
PT J
AU Kawel, N
Nacif, M
Santini, F
Liu, ST
Bremerich, J
Arai, AE
Bluemke, DA
AF Kawel, Nadine
Nacif, Marcelo
Santini, Francesco
Liu, Songtao
Bremerich, Jens
Arai, Andrew E.
Bluemke, David A.
TI Partition coefficients for gadolinium chelates in the normal myocardium:
Comparison of gadopentetate dimeglumine and gadobenate dimeglumine
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE T1 mapping; modified Look-Locker inversion recovery; partition
coefficient; gadopentetate dimeglumine; gadobenate dimeglumine
ID CARDIOVASCULAR MAGNETIC-RESONANCE; GD-DTPA; HEART-FAILURE; FIBROSIS;
HUMANS; T-1; ASSOCIATION; DISEASE; VOLUME; BLOOD
AB Purpose: To evaluate the influence of contrast agents with different relaxivity on the partition coefficient (?) and timing of equilibration using a modified Look-Locker inversion recovery (MOLLI) sequence in cardiac magnetic resonance imaging (MRI). Materials and Methods: MOLLI was acquired in 20 healthy subjects (1.5T) at the mid-ventricular short axis precontrast and 5, 10, 20, 25, and 30 minutes after administration of a bolus of 0.15 mmol/kg gadobenate dimeglumine (Gd-BOPTA) (n = 10) or gadopentetate dimeglumine (Gd-DTPA) (n = 10). T1 times were measured in myocardium and blood pool. ? was approximated by ?R1myocardium/?R1blood. Values for Gd-BOPTA and Gd-DTPA were compared. Interobserver agreement was evaluated (intraclass correlation coefficient [ICC]). Results: T1 times of myocardium and blood pool (P < 0.001) and ? (0.42 +/- 0.03 and 0.47 +/- 0.04, respectively, P < 0.001; excluding 5 minutes for Gd-BOPTA) were significantly lower for Gd-BOPTA than Gd-DTPA. The ?(Gd-DTPA) showed no significant variation between 5 and 30 minutes. The ?(Gd-BOPTA) values were significantly lower at 5 minutes compared to other times (0.38 vs. 0.42; P < 0.05). Interobserver agreement for ? values was excellent with Gd-BOPTA (ICC = 0.818) and good for Gd-DTPA (ICC = 0.631). Conclusion: The ?(Gd-BOPTA) values were significantly lower compared to ?(Gd-DTPA) at the same administered dose. Using Gd-BOPTA, the equilibrium between myocardium and blood pool was not achieved at 5 minutes postcontrast. J. Magn. Reson. Imaging 2012;36:733737. (C) 2012 Wiley Periodicals, Inc.
C1 [Kawel, Nadine; Nacif, Marcelo; Liu, Songtao; Bluemke, David A.] NIH, Bethesda, MD 20892 USA.
[Santini, Francesco] Univ Basel Hosp, Dept Radiol Phys, CH-4031 Basel, Switzerland.
[Liu, Songtao; Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, Mol Biomediacal Imaging Lab, Bethesda, MD USA.
[Bremerich, Jens] Univ Basel Hosp, Dept Radiol, CH-4031 Basel, Switzerland.
[Arai, Andrew E.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Bluemke, DA (reprint author), NIH, Bldg 10,Clin Ctr,10 Ctr Dr, Bethesda, MD 20892 USA.
EM bluemked@cc.nih.gov
OI Bremerich, Jens/0000-0002-1002-8483; Bluemke, David/0000-0002-8323-8086
FU National Institutes of Health (Bethesda, MD)
FX Contract grant sponsor: National Institutes of Health (Bethesda, MD),
intramural research program.
NR 18
TC 9
Z9 9
U1 0
U2 1
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 2012
VL 36
IS 3
BP 733
EP 737
DI 10.1002/jmri.23651
PG 5
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 994MM
UT WOS:000307934900024
PM 22488770
ER
PT J
AU Shan, L
Chopra, A
Leung, K
Eckelman, WC
Menkens, AE
AF Shan, Liang
Chopra, Arvind
Leung, Kam
Eckelman, William C.
Menkens, Anne E.
TI Characterization of nanoparticle-based contrast agents for molecular
magnetic resonance imaging
SO JOURNAL OF NANOPARTICLE RESEARCH
LA English
DT Review
DE Contrast agent; Nanoparticles; Characterization; Molecular imaging; MRI
ID SUPERPARAMAGNETIC IRON-OXIDE; BIOLOGICAL APPLICATIONS; TOXICITY
ASSESSMENT; DRUG-DELIVERY; ANIMAL-MODELS; MRI; CANCER; NANOMATERIALS;
PARAMETERS; PARTICLES
AB The development of molecular imaging agents is currently undergoing a dramatic expansion. As of October 2011, similar to 4,800 newly developed agents have been synthesized and characterized in vitro and in animal models of human disease. Despite this rapid progress, the transfer of these agents to clinical practice is rather slow. To address this issue, the National Institutes of Health launched the Molecular Imaging and Contrast Agents Database (MICAD) in 2005 to provide freely accessible online information regarding molecular imaging probes and contrast agents for the imaging community. While compiling information regarding imaging agents published in peer-reviewed journals, the MICAD editors have observed that some important information regarding the characterization of a contrast agent is not consistently reported. This makes it difficult for investigators to evaluate and meta-analyze data generated from different studies of imaging agents, especially for the agents based on nanoparticles. This article is intended to serve as a guideline for new investigators for the characterization of preclinical studies performed with nanoparticle-based MRI contrast agents. The common characterization parameters are summarized into seven categories: contrast agent designation, physicochemical properties, magnetic properties, in vitro studies, animal studies, MRI studies, and toxicity. Although no single set of parameters is suitable to define the properties of the various types of contrast agents, it is essential to ensure that these agents meet certain quality control parameters at the preclinical stage, so that they can be used without delay for clinical studies.
C1 [Shan, Liang; Chopra, Arvind; Leung, Kam; Eckelman, William C.] NIH, Mol Imaging & Contrast Agent Database, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
[Menkens, Anne E.] NCI, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Shan, L (reprint author), NIH, Mol Imaging & Contrast Agent Database, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM shanli@mail.nih.gov
NR 56
TC 8
Z9 8
U1 2
U2 44
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1388-0764
EI 1572-896X
J9 J NANOPART RES
JI J. Nanopart. Res.
PD SEP
PY 2012
VL 14
IS 9
AR 1122
DI 10.1007/s11051-012-1122-z
PG 12
WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials
Science, Multidisciplinary
SC Chemistry; Science & Technology - Other Topics; Materials Science
GA 998GP
UT WOS:000308225800051
ER
PT J
AU Barker, CA
Chang, M
Chou, JF
Zhang, ZG
Beal, K
Gutin, PH
Iwamoto, FM
AF Barker, Christopher A.
Chang, Maria
Chou, Joanne F.
Zhang, Zhigang
Beal, Kathryn
Gutin, Philip H.
Iwamoto, Fabio M.
TI Radiotherapy and concomitant temozolomide may improve survival of
elderly patients with glioblastoma
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Article
DE Concurrent; Elderly; Glioblastoma; Radiotherapy; Temozolomide
ID RECURSIVE PARTITIONING ANALYSIS; NEWLY-DIAGNOSED GLIOBLASTOMA; ADJUVANT
TEMOZOLOMIDE; RADIATION-THERAPY; MALIGNANT GLIOMA; OLDER PATIENTS; PLUS
CONCOMITANT; IN-VITRO; MULTIFORME; TRIAL
AB Survival of elderly patients with glioblastoma (GBM) is poor, but improves with tumor resection and radiotherapy (RT). Concurrent temozolomide (TMZ) chemotherapy during RT improves the survival of younger patients with GBM, but the benefit in elderly patients is unclear. Medical records of patients a parts per thousand yen65 years old with primary GBM, histologically confirmed at Memorial Sloan-Kettering Cancer Center and treated with RT, were reviewed. Survival was associated with patient (age, performance status), tumor (single or multiple), and treatment (extent of surgery, RT field, technique, fractionation and use of concurrent TMZ) characteristics in a multivariable Cox regression model. Grade a parts per thousand yen3 hematologic toxicity rates were compared to reported rates in younger patients. Median age of the 291 patients studied was 71 years. Longer survival was associated with younger age, tumor resection, and concomitant TMZ and RT (p < 0.01). Concurrent TMZ and RT improved median survival of patients with favorable prognostic factors from 12 to 21 months and from 10 to 13 months in patients 65-70 and a parts per thousand yen71 years old, respectively. Concomitant TMZ and RT increased the 2 year OS rate from 14 to 41 % and from 5 to 24 % in patients 65-70 and a parts per thousand yen71 years old, respectively. Grade 3-4 thrombocytopenia was significantly more frequent in the present cohort. Survival of elderly patients with GBM may be prolonged with the use of concomitant TMZ during RT. An ongoing randomized study will determine the benefit of this approach in a prospective fashion.
C1 [Barker, Christopher A.; Chang, Maria; Beal, Kathryn] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10065 USA.
[Chou, Joanne F.; Zhang, Zhigang] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA.
[Gutin, Philip H.] Mem Sloan Kettering Canc Ctr, Dept Neurosurg, New York, NY 10065 USA.
[Iwamoto, Fabio M.] NCI, Neurooncol Branch, Bethesda, MD 20892 USA.
RP Barker, CA (reprint author), Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, 1275 York Ave, New York, NY 10065 USA.
EM barkerc@mskcc.org
RI Barker, Christopher/I-9477-2012;
OI Barker, Christopher/0000-0003-1882-1088
FU Memorial Sloan-Kettering Cancer Center Brain Tumor Center Medical
Student Summer Fellowship
FX Presented in part at the 52nd annual meeting of the American Society for
Radiation Oncology meeting in San Diego, CA, on November 2, 2010. This
study was supported in part by the Memorial Sloan-Kettering Cancer
Center Brain Tumor Center Medical Student Summer Fellowship (M.C.).
NR 28
TC 29
Z9 29
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-594X
J9 J NEURO-ONCOL
JI J. Neuro-Oncol.
PD SEP
PY 2012
VL 109
IS 2
BP 391
EP 397
DI 10.1007/s11060-012-0906-4
PG 7
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 998OO
UT WOS:000308250200021
PM 22688802
ER
PT J
AU Maccecchini, ML
Chang, MY
Pan, C
John, V
Zetterberg, H
Greig, NH
AF Maccecchini, Maria L.
Chang, Mee Young
Pan, Catherine
John, Varghese
Zetterberg, Henrik
Greig, Nigel H.
TI Posiphen as a candidate drug to lower CSF amyloid precursor protein,
amyloid-beta peptide and tau levels: target engagement, tolerability and
pharmacokinetics in humans
SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
LA English
DT Article
ID MILD COGNITIVE IMPAIRMENT; HUMAN CEREBROSPINAL-FLUID; APP TRANSGENIC
MICE; ALZHEIMERS-DISEASE; ANTICHOLINESTERASE ACTIVITIES;
PARKINSONS-DISEASE; RESPONSIVE ELEMENT; ANTIPODAL ISOMERS;
MESSENGER-RNA; PHENSERINE
AB Aim A first in human study to evaluate tolerability and pharmacokinetics followed by an early proof of mechanism (POM) study to determine whether the small orally, available molecule, Posiphen tartrate (Posiphen), lowers secreted (s) amyloid-beta precursor protein (APP) alpha and -beta, amyloid-beta peptide (A beta), tau (tau) and inflammatory markers in CSF of patients with mild cognitive impairment (MCI).
Study design Posiphen single and multiple ascending dose phase 1 randomised, double blind, placebo-controlled safety, tolerance, pharmacokinetic studies were undertaken in a total of 120 healthy volunteers to define a dose that was then used in a small non-randomised study of five MCI subjects, used as their own controls, to define target engagement.
Main outcome measures Pharmacodynamic: sAPP alpha, sAPP beta, A beta(42), tau (total (t) and phosphorylated (p)) and inflammatory marker levels were time-dependently measured over 12 h and compared prior to and following 10 days of oral Posiphen treatment in four MCI subjects who completed the study. Pharmacokinetic: plasma and CSF drug and primary metabolite concentrations with estimated brain levels extrapolated from steady-state drug administration in rats.
Results Posiphen proved well tolerated and significantly lowered CSF levels of sAPP alpha, sAPPb, t-tau, p-tau and specific inflammatory markers, and demonstrated a trend to lower CSF A beta(42).
Conclusions These results confirm preclinical POM studies, demonstrate that pharmacologically relevant drug/metabolite levels reach brain and support the continued clinical optimisation and evaluation of Posiphen for MCI and Alzheimer's disease.
C1 [Greig, Nigel H.] NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
[Maccecchini, Maria L.; Chang, Mee Young] QR Pharma Inc, Berwyn, PA USA.
[Pan, Catherine] Inarian Neurodiagnost LLC, Mercer Isl, WA USA.
[John, Varghese] Buck Inst Res Aging, Alzheimers Drug Discovery Network, Novato, CA USA.
[Zetterberg, Henrik] Sahlgrenska Univ, Hosp Molndal, Clin Neurochem Lab, Molndal, Sweden.
RP Greig, NH (reprint author), NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program,NIH, 251 Bayview Blvd,Room 05C220, Baltimore, MD 21224 USA.
EM maccecchini@qrpharma.com; greign@grc.nia.nih.gov
FU QR Pharma, Inc.; Swedish Research Council [K2010-63P-21562-01-4,
K2011-61X-20401-05-6]; Swedish State Support for Clinical Research;
Intramural Research Program, National Institute on Aging, NIH
FX This work was supported in part by QR Pharma, Inc. Henrik Zetterberg was
supported by the Swedish Research Council (grant numbers
K2010-63P-21562-01-4 and K2011-61X-20401-05-6) and the Swedish State
Support for Clinical Research. Nigel H Greig was supported by the
Intramural Research Program, National Institute on Aging, NIH.
NR 43
TC 13
Z9 15
U1 1
U2 6
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-3050
J9 J NEUROL NEUROSUR PS
JI J. Neurol. Neurosurg. Psychiatry
PD SEP
PY 2012
VL 83
IS 9
BP 894
EP 902
DI 10.1136/jnnp-2012-302589
PG 9
WC Clinical Neurology; Psychiatry; Surgery
SC Neurosciences & Neurology; Psychiatry; Surgery
GA 988QY
UT WOS:000307506800013
PM 22791904
ER
PT J
AU Arnardottir, ES
Nikonova, EV
Shockley, KR
Anafi, RC
Podtelezhnikov, AA
Tanis, K
Stone, DJ
Maislin, G
Gislason, T
Renger, J
Winrow, C
Pack, AI
AF Arnardottir, E. S.
Nikonova, E. V.
Shockley, K. R.
Anafi, R. C.
Podtelezhnikov, A. A.
Tanis, K.
Stone, D. J.
Maislin, G.
Gislason, T.
Renger, J.
Winrow, C.
Pack, A. I.
TI Response to sleep deprivation and recovery sleep: human blood biomarkers
SO JOURNAL OF SLEEP RESEARCH
LA English
DT Meeting Abstract
CT 21st Congress of the European-Sleep-Research-Society
CY SEP 04-08, 2012
CL Paris, FRANCE
SP European Sleep Res Soc
C1 [Arnardottir, E. S.; Gislason, T.] Landspitali Univ Hosp, Reykjavik, Iceland.
[Nikonova, E. V.; Renger, J.; Winrow, C.] Merck Res Labs, West Point, NY USA.
[Shockley, K. R.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
[Anafi, R. C.; Podtelezhnikov, A. A.; Tanis, K.; Stone, D. J.; Maislin, G.; Pack, A. I.] Ctr Sleep & Circadian Neurobiol, Philadelphia, PA USA.
RI Winrow, Christopher/K-1864-2014
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 0962-1105
J9 J SLEEP RES
JI J. Sleep Res.
PD SEP
PY 2012
VL 21
SU 1
SI SI
BP 38
EP 38
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 994VV
UT WOS:000307963200087
ER
PT J
AU Dagostino, A
Manni, R
Faraci, G
Terzaghi, M
Cavallotti, S
Castelnovo, A
Ranieri, R
Marcatili, M
Scarone, S
AF Dagostino, A.
Manni, R.
Faraci, G.
Terzaghi, M.
Cavallotti, S.
Castelnovo, A.
Ranieri, R.
Marcatili, M.
Scarone, S.
TI Changing perspectives in rapid eye movement behaviour disorder
SO JOURNAL OF SLEEP RESEARCH
LA English
DT Meeting Abstract
CT 21st Congress of the European-Sleep-Research-Society
CY SEP 04-08, 2012
CL Paris, FRANCE
SP European Sleep Res Soc
C1 [Dagostino, A.; Cavallotti, S.; Scarone, S.] Univ Milan, Milan, Italy.
[Manni, R.; Terzaghi, M.] Natl Inst Neurol C Mondino, Pavia, Italy.
[Faraci, G.] NIMH, Bethesda, MD 20892 USA.
[Castelnovo, A.; Ranieri, R.; Marcatili, M.] San Paolo Hosp, Milan, Italy.
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 0962-1105
J9 J SLEEP RES
JI J. Sleep Res.
PD SEP
PY 2012
VL 21
SU 1
SI SI
BP 189
EP 189
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 994VV
UT WOS:000307963200451
ER
PT J
AU Iyer, LM
Aravind, L
AF Iyer, Lakshminarayan M.
Aravind, L.
TI Insights from the architecture of the bacterial transcription apparatus
SO JOURNAL OF STRUCTURAL BIOLOGY
LA English
DT Article
DE RNA polymerase; Beta barrel; Two component system; Activators;
Transcription factors; Mobile elements; ATPases
ID HORIZONTAL GENE-TRANSFER; DNA-BINDING-DOMAINS; STREPTOMYCES-COELICOLOR
A3(2); RNA-POLYMERASE HOLOENZYME; BACILLUS-SUBTILIS; ESCHERICHIA-COLI;
CRYSTAL-STRUCTURE; STRUCTURAL BASIS; REGULATORY NETWORKS; SIGMA-FACTOR
AB We provide a portrait of the bacterial transcription apparatus in light of the data emerging from structural studies, sequence analysis and comparative genomics to bring out important but underappreciated features. We first describe the key structural highlights and evolutionary implications emerging from comparison of the cellular RNA polymerase subunits with the RNA-dependent RNA polymerase involved in RNAi in eukaryotes and their homologs from newly identified bacteria: selfish elements. We describe some previously unnoticed domains and the possible evolutionary stages leading to the RNA polymerases of extant life forms. We then present the case for the ancient orthology of the basal transcription factors, the sigma factor and TFIIB, in the bacterial and the archaeo-eukaryotic lineages. We also present a synopsis of the structural and architectural taxonomy of specific transcription factor; and their genome-scale demography. In this context, we present certain notable deviations from the otherwise invariant proteome-wide trends in transcription factor distribution and use it to predict the presence of an unusual lineage-specifically expanded signaling system in certain firmicutes like Paenibacillus. We then discuss the intersection between functional properties of transcription factors and the organization of transcriptional networks. Finally, we present some of the interesting evolutionary conundrums posed by our newly gained understanding of the bacterial transcription apparatus and potential areas for future explorations. Published by Elsevier Inc.
C1 [Iyer, Lakshminarayan M.; Aravind, L.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Aravind, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38A,Room 5N50, Bethesda, MD 20894 USA.
EM aravind@mail.nih.gov
FU National Library of Medicine, National Institutes of Health, USA
FX Work by the authors is supported by the intra-mural funds of the
National Library of Medicine, National Institutes of Health, USA.
NR 163
TC 10
Z9 11
U1 2
U2 21
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1047-8477
EI 1095-8657
J9 J STRUCT BIOL
JI J. Struct. Biol.
PD SEP
PY 2012
VL 179
IS 3
SI SI
BP 299
EP 319
DI 10.1016/j.jsb.2011.12.013
PG 21
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 998VJ
UT WOS:000308268200007
PM 22210308
ER
PT J
AU Ozbabacan, SEA
Keskin, O
Nussinov, R
Gursoy, A
AF Ozbabacan, Saliha Ece Acuner
Keskin, Ozlem
Nussinov, Ruth
Gursoy, Attila
TI Enriching the human apoptosis pathway by predicting the structures of
protein-protein complexes
SO JOURNAL OF STRUCTURAL BIOLOGY
LA English
DT Article
DE Apoptosis; Protein-protein interaction; Protein-protein complex;
Signaling network; PRISM; 3D structure
ID RECEPTOR-MEDIATED APOPTOSIS; MITOCHONDRIAL APOPTOSIS; BCL-2 FAMILY;
WEB-SERVER; INTERFACES; SCALE; FADD; TNF; FAS; EVOLUTIONARY
AB Apoptosis is a matter of life and death for cells and both inhibited and enhanced apoptosis may be involved in the pathogenesis of human diseases. The structures of protein-protein complexes in the apoptosis signaling pathway are important as the structural pathway helps in understanding the mechanism of the regulation and information transfer, and in identifying targets for drug design. Here, we aim to predict the structures toward a more informative pathway than currently available. Based on the 3D structures of complexes in the target pathway and a protein-protein interaction modeling tool which allows accurate and proteome-scale applications, we modeled the structures of 29 interactions, 21 of which were previously unknown. Next, 27 interactions which were not listed in the KEGG apoptosis pathway were predicted and subsequently validated by the experimental data in the literature. Additional interactions are also predicted. The multi-partner hub proteins are analyzed and interactions that can and cannot co-exist are identified. Overall, our results enrich the understanding of the pathway with interactions and provide structural details for the human apoptosis pathway. They also illustrate that computational modeling of protein-protein interactions on a large scale can help validate experimental data and provide accurate, structural atom-level detail of signaling pathways in the human cell. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Ozbabacan, Saliha Ece Acuner; Keskin, Ozlem; Gursoy, Attila] Koc Univ, Ctr Computat Biol & Bioinformat, TR-34450 Rumelifeneri Yolu, Sariyer Istanbu, Turkey.
[Ozbabacan, Saliha Ece Acuner; Keskin, Ozlem; Gursoy, Attila] Koc Univ, Coll Engn, TR-34450 Rumelifeneri Yolu, Sariyer Istanbu, Turkey.
[Nussinov, Ruth] NCI, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel.
RP Keskin, O (reprint author), Koc Univ, Ctr Computat Biol & Bioinformat, TR-34450 Rumelifeneri Yolu, Sariyer Istanbu, Turkey.
EM okeskin@ku.edu.tr; agursoy@ku.edu.tr
RI Acuner Ozbabacan, Saliha Ece/I-3464-2012; Gursoy, Attila/E-9565-2015
OI Gursoy, Attila/0000-0002-2297-2113
FU Turkish Academy of Sciences; Scientific and Technological Research
Council of Turkey [109T343, 109E207]; National Cancer Institute,
National Institutes of Health [HHSN261200800001E]; NIH, National Cancer
Institute, Center for Cancer Research
FX This work was supported by an award from the Turkish Academy of Sciences
to Ozlem Keskin and the Scientific and Technological Research Council of
Turkey Fellowship to Saliha Ece Acuner Ozbabacan (Grant Nos.: 109T343
and 109E207). 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. This research was supported (in part) by the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research.
NR 52
TC 17
Z9 17
U1 0
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1047-8477
EI 1095-8657
J9 J STRUCT BIOL
JI J. Struct. Biol.
PD SEP
PY 2012
VL 179
IS 3
SI SI
BP 338
EP 346
DI 10.1016/j.jsb.2012.02.002
PG 9
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 998VJ
UT WOS:000308268200010
PM 22349545
ER
PT J
AU Vitiello, B
Riddle, MA
Yenokyan, G
Axelson, DA
Wagner, KD
Joshi, P
Walkup, JT
Luby, J
Birmaher, B
Ryan, ND
Emslie, G
Robb, A
Tillman, R
AF Vitiello, Benedetto
Riddle, Mark A.
Yenokyan, Gayane
Axelson, David A.
Wagner, Karen D.
Joshi, Paramjit
Walkup, John T.
Luby, Joan
Birmaher, Boris
Ryan, Neal D.
Emslie, Graham
Robb, Adelaide
Tillman, Rebecca
TI Treatment Moderators and Predictors of Outcome in the Treatment of Early
Age Mania (TEAM) Study
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Article
DE bipolar; treatment; predictors; moderators
ID BIPOLAR DISORDER PHENOTYPE; RANDOMIZED CLINICAL-TRIALS; ADOLESCENTS;
CHILDREN; EFFICACY; METAANALYSIS; DEPRESSION; SCALE
AB Objective: Both the diagnosis and treatment of bipolar disorder in youth remain the subject of debate. In the Treatment of Early Age Mania (TEAM) study, risperidone was more effective than lithium or divalproex in children diagnosed with bipolar mania and highly comorbid with attention-deficit/hyperactivity disorder (ADHD). We searched for treatment moderators and predictors of outcome. Method: TEAM was a multi-site, 8-week, randomized clinical trial of risperidone, lithium, or divalproex in 279 medication-naive patients, aged 6 through 15 years, with a DSM-IV diagnosis of bipolar disorder currently in manic or mixed phase. Outcome measures included binary end-of-treatment responder status and change in the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS) Mania Rating Scale (KMRS). Baseline demographics and clinical characteristics were tested as modifiers of treatment effect and as overall predictors of outcome. Results: Moderator effects were detected for site, ADHD, and obesity. Across sites, the response ratio (RR) for risperidone versus lithium ranged from 1.2 (95% confidence interval [CI] = 0.8-1.7) to 8.3 (95% CI = 1.1-60.8), and for risperidone versus divalproex from 1.3 (95% CI = 0.8-2.2) to 10.5 (95% CI = 1.4-77.7). The RR for risperidone versus lithium was 2.1 for patients with ADHD, but 1.0 for those without ADHD, and 2.3 (95% CI = 1.6-3.3) for nonobese patients, but 1.1 (95% CI = 0.6-2.0) for obese ones. Older age and less severe ADHD symptoms were associated with greater improvement on the KMRS. Conclusions: Risperidone was more effective than lithium or divalproex across the demographics and clinical characteristics of the sample, but the magnitude of its effect was influenced by site-related characteristics and presence of ADHD. Clinical trial registration information-Treatment of Early Age Mania; http://clinicaltrials.gov/; NCT00057681. J. Am. Acad. Child Adolesc. Psychiatry, 2012;51(9): 867-878.
C1 [Vitiello, Benedetto] NIMH, Bethesda, MD 20892 USA.
[Riddle, Mark A.; Yenokyan, Gayane] Johns Hopkins Univ, Baltimore, MD 21218 USA.
[Axelson, David A.; Birmaher, Boris; Ryan, Neal D.] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Wagner, Karen D.] Univ Texas Galveston, Galveston, TX USA.
[Joshi, Paramjit; Robb, Adelaide] George Washington Univ, Children Natl Med Ctr, Washington, DC 20052 USA.
[Walkup, John T.] Cornell Univ, Ithaca, NY 14853 USA.
[Luby, Joan; Tillman, Rebecca] Washington Univ, St Louis, MO 63130 USA.
[Emslie, Graham] Univ Texas SW Med Ctr, Dallas, TX USA.
RP Vitiello, B (reprint author), NIMH, Room 7147,6001 Execut Blvd, Bethesda, MD 20892 USA.
EM bvitiell@mail.nih.gov
OI Yenokyan, Gayane/0000-0003-1482-5612
FU NIMH [U01 MH064846, U01 MH064850, U01 MH064851, U01 MH064868, U01
MH064869, U01 MH064887, U01 MH064911]; National Institute of Child
Health and Human Development (NICHD); NIMH; Tourette Syndrome
Association (TSA); TSA; National Alliance for Research on Schizophrenia
and Depression (NARSAD); Communities Healing Adolescent Depression and
Suicide (CHADS) Coalition; Sidney R. Baer Foundation; BioMarin; Eli
Lilly and Co.; Forest Laboratories; GlaxoSmithKline; Somerset;
Bristol-Myers Squibb; Merck; Schering Plough; Janssen; Supernus; Otsuka;
Johnson and Johnson; Eunice Kennedy Shriver National Institute of Child
Health and Human Development (NICHD)
FX This study received funding from NIMH cooperative agreement grants U01
MH064846, U01 MH064850, U01 MH064851, U01 MH064868, U01 MH064869, U01
MH064887, and U01 MH064911.; Dr. Riddle has served as a member of a Data
and Safety Monitoring Board (DSMB) for studies sponsored by the National
Institute of Child Health and Human Development (NICHD). He has served
on a committee of the Institute of Medicine, has provided expert witness
testimony for Teva Canada, and has received aripiprazole from
Bristol-Myers Squibb for an NIMH-sponsored study. Dr. Wagner has
received honoraria from the American Psychiatric Association, Physicians
Postgraduate Press, CMP Medico, the American Academy of Child and
Adolescent Psychiatry (AACAP), Doctors Hospital at Renaissance, UBM
Medico, Quontia Communications, Continuing Medical Education (CME) LLC,
the Nevada Psychiatric Association, Slack Inc., Mercy, Hospital
Universitario Roman y Cajal, the Las Vegas Psychiatric Society, and
Partners Healthcare. Dr. Walkup has served on the advisory board and
speakers' bureau for and has received grant or research support from the
Tourette Syndrome Association (TSA). He has received honoraria and
travel funding from TSA. He has received free drug and placebo from Eli
Lilly and Co., Pfizer, and Abbott for NIMH-funded studies. He has served
as a consultant for Shire and has received royalties from Guilford Press
and Oxford University Press. Dr. Luby has received grant or research
support from NIMH, the National Alliance for Research on Schizophrenia
and Depression (NARSAD), the Communities Healing Adolescent Depression
and Suicide (CHADS) Coalition, and the Sidney R. Baer Foundation. She
has served as a consultant for the Food and Drugs Administration (FDA)
Advisory Board. Dr. Emslie has received research support from NIMH,
BioMarin, Eli Lilly and Co., Forest Laboratories, GlaxoSmithKline, and
Somerset. He has served as a consultant for Biobehavioral Diagnostics
Inc., Bristol-Myers Squibb, Eli Lilly and Co., GlaxoSmithKline,
Integrated Neuroscience Consortium (INC) Research Inc., Lundbeck,
Pfizer, Seaside Therapeutics, Shire, Valeant, and Wyeth. He has served
on the speakers' bureau for Forest Laboratories. Dr. Birmaher has
received research grant support from NIMH, royalties from Random House
and Lippincott Williams and Wilkins, and has served as a consultant for
Schering Plough. Dr. Robb has served on the boards of Eli Lilly and Co.,
Bristol-Myers Squibb, Lundbeck, Otsuka, Shinogi, and McNeil Pediatrics.
She has served as a consultant for Lundbeck, has provided expert
testimony for a case on antipsychotic use, has served on the data safety
monitoring board for Otsuka, and has received grant support from
Bristol-Myers Squibb, Merck, Schering Plough, GlaxoSmithKline, Janssen,
Supernus, Otsuka, Johnson and Johnson, and Forest Laboratories. She has
received a contract for research from the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (NICHD), has
served as speakers' bureaus for Bristol-Myers Squibb, Eli Lilly and Co.,
and McNeil Pediatrics, and has received royalties from Epocrates. She
has received payment for development and education presentations from
the University of Texas, AACAP, and the American Academy of Pediatrics
(AAP), and has served on the program committee for the American
Psychiatric Association annual meeting. Drs. Vitiello, Yenokyan,
Axelson, Joshi, and Ryan, and Ms. Tillman report no biomedical financial
interests or potential conflicts of interest.
NR 26
TC 16
Z9 16
U1 1
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0890-8567
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD SEP
PY 2012
VL 51
IS 9
BP 867
EP 878
DI 10.1016/j.jaac.2012.07.001
PG 12
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 995ZW
UT WOS:000308054800005
PM 22917200
ER
PT J
AU Massoudi, BL
Goodman, KW
Gotham, IJ
Holmes, JH
Lang, L
Miner, K
Potenziani, DD
Richards, J
Turner, AM
Fu, PC
AF Massoudi, Barbara L.
Goodman, Kenneth W.
Gotham, Ivan J.
Holmes, John H.
Lang, Lisa
Miner, Kathleen
Potenziani, David D.
Richards, Janise
Turner, Anne M.
Fu, Paul C.
TI An informatics agenda for public health: summarized recommendations from
the 2011 AMIA PHI Conference
SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
LA English
DT Article
AB The AMIA Public Health Informatics 2011 Conference brought together members of the public health and health informatics communities to revisit the national agenda developed at the AMIA Spring Congress in 2001, assess the progress that has been made in the past decade, and develop recommendations to further guide the field. Participants met in five discussion tracks: technical framework; research and evaluation; ethics; education, professional training, and workforce development; and sustainability. Participants identified 62 recommendations, which clustered into three key themes related to the need to (1) enhance communication and information sharing within the public health informatics community, (2) improve the consistency of public health informatics through common public health terminologies, rigorous evaluation methodologies, and competency-based training, and (3) promote effective coordination and leadership that will champion and drive the field forward. The agenda and recommendations from the meeting will be disseminated and discussed throughout the public health and informatics communities. Both communities stand to gain much by working together to use these recommendations to further advance the application of information technology to improve health.
C1 [Massoudi, Barbara L.] RTI Int, Ctr Adv Hlth IT, Atlanta, GA 30341 USA.
[Goodman, Kenneth W.] Univ Miami, Eth Programs, Miami, FL USA.
[Gotham, Ivan J.] New York State Dept Hlth, Healthcom Network Syst Management, Albany, NY USA.
[Holmes, John H.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Lang, Lisa] NIH, Natl Informat Ctr Hlth Serv Res & Hlth Care Techn, Natl Lib Med, Bethesda, MD 20892 USA.
[Miner, Kathleen] Emory Univ, Rollins Sch Publ Hlth, Dept Behav Sci & Hlth Educ, Atlanta, GA 30322 USA.
[Potenziani, David D.] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
[Richards, Janise] US Ctr Dis Control & Prevent, Ctr Global Hlth, Div Global HIV AIDS, Atlanta, GA USA.
[Turner, Anne M.] Univ Washington, Sch Med, NW Ctr Publ Hlth Practice, Dept Hlth Serv, Seattle, WA USA.
[Turner, Anne M.] Univ Washington, Sch Med, NW Ctr Publ Hlth Practice, Dept Med Educ, Seattle, WA USA.
[Turner, Anne M.] Univ Washington, Sch Med, NW Ctr Publ Hlth Practice, Dept Biomed Informat, Seattle, WA USA.
[Fu, Paul C.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles Biomed Res Inst, Los Angeles Cty Harbor UCLA Med Ctr,Dept Pediat, Torrance, CA USA.
[Fu, Paul C.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles Cty Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst,Dept Hlth Serv, Torrance, CA USA.
RP Massoudi, BL (reprint author), RTI Int, Ctr Adv Hlth IT, 2951 Flowers Rd,Suite 119, Atlanta, GA 30341 USA.
EM bmassoudi@rti.org
RI Fu, Paul/C-1552-2013
OI Fu, Paul/0000-0001-5772-047X
FU Robert Wood Johnson Foundation [68883]
FX The AMIA PHI 2011 meeting was supported by a generous donation from the
Robert Wood Johnson Foundation Grant Number 68883.
NR 8
TC 11
Z9 11
U1 0
U2 12
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1067-5027
J9 J AM MED INFORM ASSN
JI J. Am. Med. Inf. Assoc.
PD SEP
PY 2012
VL 19
IS 5
BP 688
EP 695
DI 10.1136/amiajnl-2011-000507
PG 8
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 994MJ
UT WOS:000307934600002
PM 22395299
ER
PT J
AU Kirklin, JK
Naftel, DC
Pagani, FD
Kormos, RL
Stevenson, L
Miller, M
Young, JB
AF Kirklin, James K.
Naftel, David C.
Pagani, Francis D.
Kormos, Robert L.
Stevenson, Lynne
Miller, Marissa
Young, James B.
TI Long-term mechanical circulatory support (destination therapy): On track
to compete with heart transplantation?
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Article; Proceedings Paper
CT 92nd Annual Meeting of the American-Association-for-Thoracic-Surgery
CY APR 28-MAY 02, 2012
CL San Francisco, CA
SP Amer Assoc Thorac Surg
ID VENTRICULAR ASSIST DEVICE; QUALITY-OF-LIFE; INTERMACS ANNUAL-REPORT;
INTERAGENCY REGISTRY; FAILURE PATIENTS; PREDICTORS; EVOLUTION; IMPLANTS;
BRIDGE
AB Objectives: Average 2-year survival after cardiac transplantation is approximately 80%. The evolution and subsequent approval of larger pulsatile and, more recently, continuous flow mechanical circulatory support (MCS) technology for destination therapy (DT) offers the potential for triage of some patients awaiting cardiac transplantation to DT.
Methods: The National Heart, Lung, and Blood Institute Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) is a national multi-institutional study of long-term MCS. Between June 2006 and December 2011, 127 pulsatile and 1160 continuous flow pumps (24% of total primary left ventricular assist devices [LVADs]) carried an initial strategy of DT therapy.
Results: By multivariable analysis, risk factors (P <. 05) for mortality after DT included older age, larger body mass index, history of cancer, history of cardiac surgery, INTERMACS level I (cardiogenic shock), dialysis, increased blood urea nitrogen, use of a pulsatile flow device, and use of a right ventricular assist device (RVAD). Among patients with a continuous flow LVAD who were not in cardiogenic shock, a particularly favorable survival was associated with no cancer, patients not in cardiogenic shock, and blood urea nitrogen less than 50 mg/dL, resulting in 1- and 2-year survivals of 88% and 80%.
Conclusions: (1) Evolution from pulsatile to continuous flow technology has dramatically improved 1- and 2-year survivals; (2) DT is not appropriate for patients with rapid hemodynamic deterioration or severe right ventricular failure; (3) important subsets of patients with continuous flow DT now enjoy survival that is competitive with heart transplantation out to about 2 years. (J Thorac Cardiovasc Surg 2012;144:584-603)
C1 [Kirklin, James K.; Naftel, David C.] Univ Alabama Birmingham, Birmingham, AL 35294 USA.
[Pagani, Francis D.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Kormos, Robert L.] Univ Pittsburgh, Pittsburgh, PA USA.
[Stevenson, Lynne] Brigham & Womens Med Ctr, Boston, MA USA.
[Miller, Marissa] NHLBI, Bethesda, MD 20892 USA.
[Young, James B.] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
RP Kirklin, JK (reprint author), Univ Alabama Birmingham, THT 760,1900 Univ Blvd, Birmingham, AL 35294 USA.
EM jkirklin@uab.edu
FU NHLBI NIH HHS [HHSN268201100025C]; PHS HHS [268200548198C]
NR 25
TC 122
Z9 124
U1 1
U2 16
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5223
J9 J THORAC CARDIOV SUR
JI J. Thorac. Cardiovasc. Surg.
PD SEP
PY 2012
VL 144
IS 3
BP 584
EP 603
DI 10.1016/j.jtcvs.2012.05.044
PG 20
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 996DL
UT WOS:000308064200041
PM 22795459
ER
PT J
AU Finzi, A
Pacheco, B
Xiang, SH
Pancera, M
Herschhorn, A
Wang, LP
Zeng, X
Desormeaux, A
Kwong, PD
Sodroski, J
AF Finzi, Andres
Pacheco, Beatriz
Xiang, Shi-Hua
Pancera, Marie
Herschhorn, Alon
Wang, Liping
Zeng, Xing
Desormeaux, Anik
Kwong, Peter D.
Sodroski, Joseph
TI Lineage-Specific Differences between Human and Simian Immunodeficiency
Virus Regulation of gp120 Trimer Association and CD4 Binding
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID ENVELOPE GLYCOPROTEIN TRIMERS; INFECTIOUS MOLECULAR CLONES;
T-LYMPHOTROPIC RETROVIRUS; HIV-1 GP120; AIDS PATIENTS; INNER DOMAIN;
HTLV-III; TRANSMEMBRANE GLYCOPROTEIN; CD4-BOUND CONFORMATION; MACROPHAGE
TROPISM
AB Metastable conformations of the gp120 and gp41 envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SW) must be maintained in the unliganded state of the envelope glycoprotein trimer. Binding of gp120 to the primary receptor, CD4, triggers the transition to an open conformation of the trimer, promoting interaction with the CCR5 chemokine receptor and ultimately leading to gp41-mediated virus-cell membrane fusion and entry. Topological layers in the gp120 inner domain contribute to gp120-trimer association in the unliganded state and to CD4 binding. Here we describe similarities and differences between HIV-1 and SIVmac gp120. In both viruses, the gp120 N/C termini and the inner domain beta-sandwich and layer 2 support the noncovalent association of gp120 with the envelope glycoprotein trimer. Layer 1 of the SIVmac gp120 inner domain contributes more to trimer association than the corresponding region of HIV-1 gp120. On the other hand, layer 1 plays an important role in stabilizing the CD4-bound conformation of HIV-1 but not SIVmac gp120 and thus contributes to HIV-1 binding to CD4. In SIVmac, CD4 binding is instead enhanced by tryptophan 375, which fills the Phe 43 cavity of gp120. Activation of SIVmac by soluble CD4 is dependent on tryptophan 375 and on layer 1 residues that determine a tight association of gp120 with the trimer. Distinct biological requirements for CD4 usage have resulted in lineage-specific differences in the HIV-1 and SIV gp120 structures that modulate trimer association and CD4 binding.
C1 [Finzi, Andres; Pacheco, Beatriz; Xiang, Shi-Hua; Herschhorn, Alon; Wang, Liping; Zeng, Xing; Sodroski, Joseph] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Sodroski, Joseph] Harvard Univ, Sch Med, Div Aids, Dept Microbiol & Immunobiol, Boston, MA USA.
[Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
[Pancera, Marie; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Sodroski, Joseph] MIT & Harvard, Massachusetts Gen Hosp, Ragon Inst, Charlestown, MA USA.
[Desormeaux, Anik] Univ Montreal, Dept Microbiol & Immunol, Montreal, PQ H3C 3J7, Canada.
RP Sodroski, J (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
EM joseph_sodroski@dfci.harvard.edu
FU VRC; NIAID; National Institutes of Health [AI24755, GM56550, AI67854];
International AIDS Vaccine Initiative; William F. McCarty-Cooper; amfAR
Mathilde Krim Fellowship in Basic Biomedical Research [107963-49-RKVA,
108092-50-RKVA]; Canada Foundation for Innovation Program [29866]; CIHR
[257792]
FX This work was supported by intramural funding by the VRC, NIAID, and by
grants from the National Institutes of Health (AI24755, GM56550, and
AI67854), by the International AIDS Vaccine Initiative, by the late
William F. McCarty-Cooper (to J.S.), and by an amfAR Mathilde Krim
Fellowship in Basic Biomedical Research (phase I, 107963-49-RKVA; phase
II, 108092-50-RKVA), by a Canada Foundation for Innovation Program
Leader grant (no. 29866), and by a CIHR operating grant, 257792, to A.F.
NR 80
TC 15
Z9 15
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 2012
VL 86
IS 17
BP 8974
EP 8986
DI 10.1128/JVI.01076-12
PG 13
WC Virology
SC Virology
GA 990JW
UT WOS:000307627800005
PM 22696649
ER
PT J
AU Earl, PL
Americo, JL
Moss, B
AF Earl, Patricia L.
Americo, Jeffrey L.
Moss, Bernard
TI Lethal Monkeypox Virus Infection of CAST/EiJ Mice Is Associated with a
Deficient Gamma Interferon Response
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID SECONDARY POXVIRUS INFECTION; CONGO BASIN; GENETIC SUSCEPTIBILITY;
SMALLPOX VACCINATION; SPECIES-SPECIFICITY; ECTROMELIA VIRUS;
IMMUNE-RESPONSE; ANIMAL-MODEL; WEST-AFRICAN; PRAIRIE DOGS
AB Monkeypox virus (MPXV) is endemic in Africa, where it causes disease in humans resembling smallpox. A recent importation of MPXV-infected animals into the United States raises the possibility of global spread. Rodents comprise the major reservoir of MPXV, and a variety of such animals, even those native to North America, are susceptible. In contrast, common inbred strains of mice, including BALB/c and C57BL/6, are greatly resistant to MPXV. However, several inbred strains of mice derived from wild mice, including CAST/EiJ, exhibit morbidity and mortality at relatively low inoculums of MPXV. Elucidating the basis for the susceptibility of CAST/EiJ mice could contribute to an understanding of MPXV pathogenicity and host defense mechanisms and enhance the value of this mouse strain as a model system for evaluation of therapeutics and vaccines. Here we compared virus dissemination and induced cytokine production in CAST/EiJ mice to those in the resistant BALB/c strain. Following intranasal infection, robust virus replication occurred in the lungs of both strains, although a relatively higher inoculum was required for BALB/c. However, while spread to other internal organs was rapid and efficient in CAST/EiJ mice, the virus was largely restricted to the lungs in BALB/c mice. Gamma interferon (IFN-gamma) and CCL5 were induced in lungs of BALB/c mice concomitant with virus replication but not in CAST/EiJ mice. The importance of IFN-gamma in protection against MPXV disease was demonstrated by the intranasal administration of the mouse cytokine to CAST/EiJ mice and the resulting protection against MPXV. Furthermore, C57BL/6 mice with inactivation of the IFN-gamma gene or the IFN-gamma receptor gene exhibited enhanced sensitivity to MPXV.
C1 [Earl, Patricia L.; Americo, Jeffrey L.; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Earl, PL (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
EM pearl@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, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health.
NR 50
TC 16
Z9 16
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 2012
VL 86
IS 17
BP 9105
EP 9112
DI 10.1128/JVI.00162-12
PG 8
WC Virology
SC Virology
GA 990JW
UT WOS:000307627800017
PM 22696658
ER
PT J
AU McDonald, SM
McKell, AO
Rippinger, CM
McAllen, JK
Akopov, A
Kirkness, EF
Payne, DC
Edwards, KM
Chappell, JD
Patton, JT
AF McDonald, Sarah M.
McKell, Allison O.
Rippinger, Christine M.
McAllen, John K.
Akopov, Asmik
Kirkness, Ewen F.
Payne, Daniel C.
Edwards, Kathryn M.
Chappell, James D.
Patton, John T.
TI Diversity and Relationships of Cocirculating Modern Human Rotaviruses
Revealed Using Large-Scale Comparative Genomics
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID SEQUENCE-INDEPENDENT AMPLIFICATION; UNITED-STATES; STRAIN SURVEILLANCE;
PORCINE ROTAVIRUS; POTENTIAL IMPACT; GENETIC-LINKAGE; BINDING DOMAIN;
GLOBAL SPREAD; VACCINATION; CHILDREN
AB Group A rotaviruses (RVs) are 11-segmented, double-stranded RNA viruses and are primary causes of gastroenteritis in young children. Despite their medical relevance, the genetic diversity of modern human RVs is poorly understood, and the impact of vaccine use on circulating strains remains unknown. In this study, we report the complete genome sequence analysis of 58 RVs isolated from children with severe diarrhea and/or vomiting at Vanderbilt University Medical Center (VUMC) in Nashville, TN, during the years spanning community vaccine implementation (2005 to 2009). The RVs analyzed include 36 GIP [8], 18 G3P [8], and 4 G12P[8] Wa-like genogroup 1 strains with VP6-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5/6 genotype constellations of I1-R1-C1-M1-A1-N1-T1-E1-H1. By constructing phylogenetic trees, we identified 2 to 5 subgenotype alleles for each gene. The results show evidence of intragenogroup gene reassortment among the cocirculating strains. However, several isolates from different seasons maintained identical allele constellations, consistent with the notion that certain RV clades persisted in the community. By comparing the genes of VUMC RVs to those of other archival and contemporary RV strains for which sequences are available, we defined phylogenetic lineages and verified that the diversity of the strains analyzed in this study reflects that seen in other regions of the world. Importantly, the VP4 and VP7 proteins encoded by VUMC RVs and other contemporary strains show amino acid changes in or near neutralization domains, which might reflect antigenic drift of the virus. Thus, this large-scale, comparative genomic study of modern human RVs provides significant insight into how this pathogen evolves during its spread in the community.
C1 [McDonald, Sarah M.; McKell, Allison O.] Virginia Tech Caril Res Inst, Roanoke, VA USA.
[McDonald, Sarah M.; McKell, Allison O.] Virginia Maryland Reg Coll Vet Med, Dept Biomed Sci & Pathobiol, Blacksburg, VA USA.
[Rippinger, Christine M.; Patton, John T.] NIAID, Rotavirus Mol Biol Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[McAllen, John K.; Akopov, Asmik; Kirkness, Ewen F.] J Craig Venter Inst, Rockville, MD USA.
[Payne, Daniel C.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Edwards, Kathryn M.; Chappell, James D.] Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA.
[Chappell, James D.] Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37212 USA.
RP McDonald, SM (reprint author), Virginia Tech Caril Res Inst, Roanoke, VA USA.
EM mcdonaldsa@vtc.vt.edu
RI Patton, John/P-1390-2014
FU Virginia Tech Carilion Research Institute; National Institute of Allergy
and Infectious Diseases, National Institutes of Health; Centers for
Disease Control and Prevention [1U01IP00022]; National Institute of
Allergy and Infectious Diseases, National Institutes of Health,
Department of Health and Human Services [HHSN272200900007C]
FX S.M.M. and A.O.M. were supported by the Virginia Tech Carilion Research
Institute. J.T.P. and C.M.R. were supported by the Intramural Research
Program of the National Institute of Allergy and Infectious Diseases,
National Institutes of Health. This project was also supported in part
by a contract from the Centers for Disease Control and Prevention
(contract no. 1U01IP00022) and by federal funds from the National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, Department of Health and Human Services (contract no.
HHSN272200900007C).
NR 56
TC 23
Z9 23
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 2012
VL 86
IS 17
BP 9148
EP 9162
DI 10.1128/JVI.01105-12
PG 15
WC Virology
SC Virology
GA 990JW
UT WOS:000307627800021
PM 22696651
ER
PT J
AU Qi, L
Davis, AS
Jagger, BW
Schwartzman, LM
Dunham, EJ
Kash, JC
Taubenberger, JK
AF Qi, Li
Davis, A. Sally
Jagger, Brett W.
Schwartzman, Louis M.
Dunham, Eleca J.
Kash, John C.
Taubenberger, Jeffery K.
TI Analysis by Single-Gene Reassortment Demonstrates that the 1918
Influenza Virus Is Functionally Compatible with a Low-Pathogenicity
Avian Influenza Virus in Mice
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID PANDEMIC INFLUENZA; A VIRUSES; HOST-RANGE; ENHANCED VIRULENCE;
IMMUNE-RESPONSE; POLYMERASE; ORIGIN; H5N1; HEMAGGLUTININ; PB2
AB The 1918-1919 "Spanish" influenza pandemic is estimated to have caused 50 million deaths worldwide. Understanding the origin, virulence, and pathogenic properties of past pandemic influenza viruses, including the 1918 virus, is crucial for current public health preparedness and future pandemic planning. The origin of the 1918 pandemic virus has not been resolved, but its coding sequences are very like those of avian influenza virus. The proteins encoded by the 1918 virus differ from typical low-pathogenicity avian influenza viruses at only a small number of amino acids in each open reading frame. In this study, a series of chimeric 1918 influenza viruses were created in which each of the eight 1918 pandemic virus gene segments was replaced individually with the corresponding gene segment of a prototypical low-pathogenicity avian influenza (LPAI) H1N1 virus in order to investigate functional compatibility of the 1918 virus genome with gene segments from an LPAI virus and to identify gene segments and mutations important for mammalian adaptation. This set of eight "7:1" chimeric viruses was compared to the parental 1918 and LPAI H1N1 viruses in intranasally infected mice. Seven of the 1918 LPAI 7:1 chimeric viruses replicated and caused disease equivalent to the fully reconstructed 1918 virus. Only the chimeric 1918 virus containing the avian influenza PB2 gene segment was attenuated in mice. This attenuation could be corrected by the single E627K amino acid change, further confirming the importance of this change in mammalian adaptation and mouse pathogenicity. While the mechanisms of influenza virus host switch, and particularly mammalian host adaptation are still only partly understood, these data suggest that the 1918 virus, whatever its origin, is very similar to avian influenza virus.
C1 [Qi, Li; Davis, A. Sally; Jagger, Brett W.; Schwartzman, Louis M.; Dunham, Eleca J.; Kash, John C.; Taubenberger, Jeffery K.] NIAID, NIH, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, Bethesda, MD 20892 USA.
RP Taubenberger, JK (reprint author), NIAID, NIH, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM taubenbergerj@niaid.nih.gov
OI Davis, Anne/0000-0001-5711-3936
FU NIH; NIAID
FX This work was supported by the intramural funds of the NIH and the
NIAID.
NR 72
TC 14
Z9 14
U1 1
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD SEP
PY 2012
VL 86
IS 17
BP 9211
EP 9220
DI 10.1128/JVI.00887-12
PG 10
WC Virology
SC Virology
GA 990JW
UT WOS:000307627800026
PM 22718825
ER
PT J
AU Warren, RD
Cotter, CA
Moss, B
AF Warren, Robin D.
Cotter, Catherine A.
Moss, Bernard
TI Reverse Genetics Analysis of Poxvirus Intermediate Transcription Factors
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID VIRUS EARLY GENES; VACCINIA VIRUS; RNA POLYMERASE; STAGE GENES;
EXPRESSION; DNA; PROTEIN; IDENTIFICATION; REPLICATION; RESOLUTION
AB Vaccinia virus transcription is regulated in three stages. An intermediate transcription factor, comprised of virus-encoded poly-peptides A8 and A23, was previously identified by in vitro analyses. To investigate its role, we engineered cells that stably expressed both subunits and complemented the replication of A8 and A23 deletion mutant viruses. Without A8 or A23, viral early gene expression and DNA replication occurred but intermediate and late gene expression and resolution of genome concatemers were not detected.
C1 [Warren, Robin D.; Cotter, Catherine A.; Moss, Bernard] 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@niaid.nih.gov
FU Division of Intramural Research, NIAID, NIH; NIH
FX Support was provided by the Division of Intramural Research, NIAID, NIH.
R.D.W. was the recipient of an NIH Intramural Fellowship to Promote
Diversity.
NR 26
TC 7
Z9 7
U1 1
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 2012
VL 86
IS 17
BP 9514
EP 9519
DI 10.1128/JVI.06902-11
PG 6
WC Virology
SC Virology
GA 990JW
UT WOS:000307627800054
PM 22740406
ER
PT J
AU Chawla, LS
Kimmel, PL
AF Chawla, Lakhmir S.
Kimmel, Paul L.
TI Acute kidney injury and chronic kidney disease: an integrated clinical
syndrome
SO KIDNEY INTERNATIONAL
LA English
DT Review
DE acute kidney injury; acute on chronic; acute renal failure; chronic
kidney disease; progression; risk factor
ID ACUTE-RENAL-FAILURE; ACUTE TUBULAR-NECROSIS; INITIAL
ISCHEMIA/REPERFUSION INJURY; LONG-TERM SURVIVAL; CARDIAC-SURGERY; SERUM
CREATININE; CELL-CYCLE; FOLLOW-UP; PROGRESSION; RECOVERY
AB The previous conventional wisdom that survivors of acute kidney injury (AKI) tend to do well and fully recover renal function appears to be flawed. AKI can cause end-stage renal disease (ESRD) directly, and increase the risk of developing incident chronic kidney disease (CKD) and worsening of underlying CKD. In addition, severity, duration, and frequency of AKI appear to be important predictors of poor patient outcomes. CKD is an important risk factor for the development and ascertainment of AKI. Experimental data support the clinical observations and the bidirectional nature of the relationships between AKI and CKD. Reductions in renal mass and nephron number, vascular insufficiency, cell cycle disruption, and maladaptive repair mechanisms appear to be important modulators of progression in patients with and without coexistent CKD. Distinction between AKI and CKD may be artificial. Consideration should be given to the integrated clinical syndrome of diminished GFR, with acute and chronic stages, where spectrum of disease state and outcome is determined by host factors, including the balance of adaptive and maladaptive repair mechanisms over time. Physicians must provide long-term follow-up to patients with first episodes of AKI, even if they presented with normal renal function.
C1 [Chawla, Lakhmir S.] George Washington Univ, Med Ctr, Dept Anesthesiol & Crit Care Med, Washington, DC 20037 USA.
[Chawla, Lakhmir S.; Kimmel, Paul L.] George Washington Univ, Med Ctr, Dept Med, Div Renal Dis & Hypertens, Washington, DC 20037 USA.
[Kimmel, Paul L.] NIDDKD, NIH, Bethesda, MD 20892 USA.
RP Chawla, LS (reprint author), George Washington Univ, Med Ctr, Dept Anesthesiol & Crit Care Med, 900 23rd St NW,RILF,G-105, Washington, DC 20037 USA.
EM minkchawla@gmail.com
NR 80
TC 200
Z9 208
U1 6
U2 45
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0085-2538
EI 1523-1755
J9 KIDNEY INT
JI Kidney Int.
PD SEP
PY 2012
VL 82
IS 5
BP 516
EP 524
DI 10.1038/ki.2012.208
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 992TS
UT WOS:000307803200005
PM 22673882
ER
PT J
AU Jacobson, KA
Costanzi, S
AF Jacobson, Kenneth A.
Costanzi, Stefano
TI New Insights for Drug Design from the X-Ray Crystallographic Structures
of G-Protein-Coupled Receptors
SO MOLECULAR PHARMACOLOGY
LA English
DT Review
ID ADENOSINE A(2A) RECEPTOR; MUSCARINIC ACETYLCHOLINE-RECEPTOR; ANGSTROM
CRYSTAL-STRUCTURE; STRUCTURE-BASED DISCOVERY; HISTAMINE H-1 RECEPTOR;
BETA(2)-ADRENERGIC RECEPTOR; EXTRACELLULAR LOOPS; OPIOID RECEPTOR;
HOMOLOGY MODELS; SQUID RHODOPSIN
AB Methodological advances in X-ray crystallography have made possible the recent solution of X-ray structures of pharmaceutically important G protein-coupled receptors (GPCRs), including receptors for biogenic amines, peptides, a nucleoside, and a sphingolipid. These high-resolution structures have greatly increased our understanding of ligand recognition and receptor activation. Conformational changes associated with activation common to several receptors entail outward movements of the intracellular side of transmembrane helix 6 (TM6) and movements of TM5 toward TM6. Movements associated with specific agonists or receptors have also been described [e.g., extracellular loop (EL) 3 in the A(2A) adenosine receptor]. The binding sites of different receptors partly overlap but differ significantly in ligand orientation, depth, and breadth of contact areas in TM regions and the involvement of the ELs. A current challenge is how to use this structural information for the rational design of novel potent and selective ligands. For example, new chemotypes were discovered as antagonists of various GPCRs by subjecting chemical libraries to in silico docking in the X-ray structures. The vast majority of GPCR structures and their ligand complexes are still unsolved, and no structures are known outside of family A GPCRs. Molecular modeling, informed by supporting information from site-directed mutagenesis and structure-activity relationships, has been validated as a useful tool to extend structural insights to related GPCRs and to analyze docking of other ligands in already crystallized GPCRs.
C1 [Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Costanzi, Stefano] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA.
EM kajacobs@helix.nih.gov
RI Jacobson, Kenneth/A-1530-2009; Costanzi, Stefano/G-8990-2013;
OI Jacobson, Kenneth/0000-0001-8104-1493; Costanzi,
Stefano/0000-0003-3183-7332
FU National Institutes of Health National Institute of Diabetes and
Digestive and Kidney Diseases [Z01-DK031126-08, Z01-DK013025-05]
FX This work was supported by the National Institutes of Health National
Institute of Diabetes and Digestive and Kidney Diseases [Grants
Z01-DK031126-08, Z01-DK013025-05].
NR 96
TC 52
Z9 52
U1 2
U2 47
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 2012
VL 82
IS 3
BP 361
EP 371
DI 10.1124/mol.112.079335
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 996FL
UT WOS:000308070100001
PM 22695719
ER
PT J
AU Zhang, SY
Surapureddi, S
Coulter, S
Ferguson, SS
Goldstein, JA
AF Zhang, Shu-Yun
Surapureddi, Sailesh
Coulter, Sherry
Ferguson, Stephen S.
Goldstein, Joyce A.
TI Human CYP2C8 Is Post-Transcriptionally Regulated by MicroRNAs 103 and
107 in Human Liver
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID PREGNANE-X-RECEPTOR; CONSTITUTIVE ANDROSTANE RECEPTOR; NUCLEAR FACTOR
4-ALPHA; HUMAN HEPATOCYTES; GLUCOCORTICOID-RECEPTOR; CYTOCHROME P4502C8;
CLINICAL-RELEVANCE; MESSENGER-RNA; EXPRESSION; METABOLISM
AB The CYP2C genes are extensively regulated at the transcriptional stage. The present study shows for the first time that CYP2Cs are also regulated post-transcriptionally by microRNAs (miRNAs). By using online search engines, we found potential miRNA response elements (MREs) in the 3'-untranslated region (3'-UTR) of the CYP2C mRNAs. Among these were a MRE for the miRNAs miR-103 and miR-107 in the 3'-UTR of human CYP2C8. CYP2C8 protein levels (measured through immunoblot analyses) did not correlate with CYP2C8 mRNA levels (measured through quantitative polymerase chain reaction analyses) in human liver samples. The translation efficiency (protein/mRNA ratio) for CYP2C8 was inversely correlated with the expression of miR-103 and miR-107. When three copies of the putative MRE from CYP2C8 were inserted downstream from a luciferase expression reporter, transfection with precursors for miR-103 or miR-107 decreased luciferase activity in primary hepatocytes, whereas transfection with antisense oligonucleotides (AsOs) for miR-103/miR-107 increased luciferase activity. As expected, there was no effect of the precursors or AsOs when three copies of the putative MRE were inserted in the reverse orientation. When precursors for miR-103/miR-107 were transfected into primary human hepatocytes, CYP2C8 protein levels were decreased, whereas AsOs increased CYP2C8 protein levels. Neither precursors nor AsOs affected CYP2C8 mRNA levels, which indicated that the effect was post-transcriptional. Putative MRE motifs were also found in the 3'-UTRs of CYP2C9 and CYP2C19, which suggested that the same miRNAs could regulate translation of other members of the CYP2C family, although to a lesser degree than CYP2C8. These results clearly show that CYP2Cs are regulated post-transcriptionally by miR-103 and miR-107.
C1 [Zhang, Shu-Yun; Surapureddi, Sailesh; Coulter, Sherry; Goldstein, Joyce A.] NIEHS, Human Metab Sect, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
[Ferguson, Stephen S.] CellzDirect Invitrogen Corp, Durham, NC USA.
RP Goldstein, JA (reprint author), NIEHS, Human Metab Sect, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
EM goldste1@niehs.nih.gov
OI Coulter, Sherry/0000-0002-2732-3470
FU Intramural Research Program of the National Institutes of Health
National Institute of Environmental Health Sciences [Z01-ES02124]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health National Institute of Environmental Health
Sciences [Project Z01-ES02124].
NR 60
TC 35
Z9 38
U1 1
U2 10
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 2012
VL 82
IS 3
BP 529
EP 540
DI 10.1124/mol.112.078386
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 996FL
UT WOS:000308070100017
PM 22723340
ER
PT J
AU Wang, GJ
Smith, L
Volkow, ND
Telang, F
Logan, J
Tomasi, D
Wong, CT
Hoffman, W
Jayne, M
Alia-Klein, N
Thanos, P
Fowler, JS
AF Wang, G. J.
Smith, L.
Volkow, N. D.
Telang, F.
Logan, J.
Tomasi, D.
Wong, C. T.
Hoffman, W.
Jayne, M.
Alia-Klein, N.
Thanos, P.
Fowler, J. S.
TI Decreased dopamine activity predicts relapse in methamphetamine abusers
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE dopamine release; early withdrawal; methamphetamine; positron emission
tomography; relapse
ID RHESUS-MONKEYS; COCAINE; BRAIN; STRIATUM; RECEPTORS; DEPENDENCE;
RECOVERY; NEUROTOXICITY; TRANSMISSION; INVOLVEMENT
AB Studies in methamphetamine (METH) abusers showed that the decreases in brain dopamine (DA) function might recover with protracted detoxification. However, the extent to which striatal DA function in METH predicts recovery has not been evaluated. Here we assessed whether striatal DA activity in METH abusers is associated with clinical outcomes. Brain DA D2 receptor (D2R) availability was measured with positron emission tomography and [C-11]raclopride in 16 METH abusers, both after placebo and after challenge with 60mg oral methylphenidate (MPH) (to measure DA release) to assess whether it predicted clinical outcomes. For this purpose, METH abusers were tested within 6 months of last METH use and then followed up for 9 months of abstinence. In parallel, 15 healthy controls were tested. METH abusers had lower D2R availability in caudate than in controls. Both METH abusers and controls showed decreased striatal D2R availability after MPH and these decreases were smaller in METH than in controls in left putamen. The six METH abusers who relapsed during the follow-up period had lower D2R availability in dorsal striatum than in controls, and had no D2R changes after MPH challenge. The 10 METH abusers who completed detoxification did not differ from controls neither in striatal D2R availability nor in MPH-induced striatal DA changes. These results provide preliminary evidence that low striatal DA function in METH abusers is associated with a greater likelihood of relapse during treatment. Detection of the extent of DA dysfunction may be helpful in predicting therapeutic outcomes. Molecular Psychiatry (2012) 17, 918-925; doi: 10.1038/mp.2011.86; published online 12 July 2011
C1 [Wang, G. J.; Logan, J.; Alia-Klein, N.; Fowler, J. S.] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
[Wang, G. J.; Fowler, J. S.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA.
[Smith, L.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA.
[Volkow, N. D.] NIDA, Off Director, Bethesda, MD 20892 USA.
[Volkow, N. D.; Telang, F.; Tomasi, D.; Wong, C. T.; Jayne, M.; Thanos, P.] NIAAA, Lab Neuroimaging, Intramural Program, Upton, NY USA.
[Hoffman, W.] Vet Adm Med Ctr, Dept Psychiat, Portland, OR USA.
RP Wang, GJ (reprint author), Brookhaven Natl Lab, Dept Med, 30 Bell Ave, Upton, NY 11973 USA.
EM gjwang@bnl.gov
RI Tomasi, Dardo/J-2127-2015
FU US Department of Energy OBER [DE-ACO2-76CH00016]; NIH [R01DA06891,
MO1RR10710, Z01AA000550]
FX The PET study was carried out at the Brookhaven National Laboratory with
infrastructure support from the US Department of Energy OBER
(DE-ACO2-76CH00016) and under support in part by NIH: R01DA06891 (Dr
Wang), MO1RR10710 (the General Clinical Research Center of Stony Brook
University) and Z01AA000550 (Dr Volkow). The authors declare no conflict
of interest.
NR 39
TC 67
Z9 69
U1 5
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD SEP
PY 2012
VL 17
IS 9
BP 918
EP 925
DI 10.1038/mp.2011.86
PG 8
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 996DI
UT WOS:000308063900008
PM 21747399
ER
PT J
AU Nair, G
Reich, DS
AF Nair, Govind
Reich, Daniel S.
TI IMPROVED VISUALIZATION OF SPINAL CORD LESIONS IN MULTIPLE SCLEROSIS
USING A T1-WEIGHTED MAGNETIZATION PREPARED RAPID GRADIENT ECHO SEQUENCE
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
C1 [Nair, Govind; Reich, Daniel S.] NINDS, NIH, Bethesda, MD 20892 USA.
RI Reich, Daniel/E-5701-2010
OI 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 2012
VL 18
IS 9
BP S18
EP S18
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 997BD
UT WOS:000308138200029
ER
PT J
AU von Geldern, G
Newsome, SD
Marasigan, RER
Oh, J
Reich, DS
Calabresi, PA
Zackowski, KM
AF von Geldern, Gloria
Newsome, Scott D.
Marasigan, Rhul Evans R.
Oh, Jiwon
Reich, Daniel S.
Calabresi, Peter A.
Zackowski, Kathleen M.
TI HOW IMPAIRED IS HAND FUNCTION IN INDIVIDUALS WITH MULTIPLE SCLEROSIS?
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
C1 [Zackowski, Kathleen M.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Marasigan, Rhul Evans R.; Zackowski, Kathleen M.] Kennedy Krieger Inst, Mot Anal Lab, Baltimore, MD USA.
[Reich, Daniel S.] NINDS, NIH, Bethesda, MD 20892 USA.
RI Reich, Daniel/E-5701-2010
OI 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 2012
VL 18
IS 9
BP S23
EP S23
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 997BD
UT WOS:000308138200039
ER
PT J
AU Wolinsky, JS
Narayana, PA
Nelson, F
Datta, S
Gates, B
Salter, AR
Conwit, R
Cutter, GR
Cofield, SS
Lublin, FD
AF Wolinsky, Jerry S.
Narayana, Ponnada A.
Nelson, Flavia
Datta, Sushmita
Gates, Brandi
Salter, Amber R.
Conwit, Robin
Cutter, Gary R.
Cofield, Stacey S.
Lublin, Fred D.
TI USING SHORT-TERM MRI MEASURES TO PREDICT LONG-TERM OUTCOMES IN THE
COMBIRX RANDOMIZED CLINICAL TRIAL
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
C1 [Salter, Amber R.; Cutter, Gary R.; Cofield, Stacey S.] Univ Alabama Birmingham, Birmingham, AL USA.
[Lublin, Fred D.] Mt Sinai Sch Med, New York, NY USA.
[Wolinsky, Jerry S.; Narayana, Ponnada A.; Nelson, Flavia; Datta, Sushmita; Gates, Brandi] Univ Texas Hlth Sci Ctr Houston, Houston, TX 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 2012
VL 18
IS 9
BP S8
EP S8
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 997BD
UT WOS:000308138200009
ER
PT J
AU Gildersleeve, JC
AF Gildersleeve, Jeffrey C.
TI GLYCOSYLTRANSFERASES Carb loading strategy is spot on
SO NATURE CHEMICAL BIOLOGY
LA English
DT News Item
ID MICROARRAYS; SPECIFICITIES; GLYCANS
C1 NCI, Biol Chem Lab, Frederick, MD 21701 USA.
RP Gildersleeve, JC (reprint author), NCI, Biol Chem Lab, Frederick, MD 21701 USA.
EM gildersj@mail.nih.gov
RI Gildersleeve, Jeffrey/N-3392-2014
NR 10
TC 1
Z9 1
U1 2
U2 11
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1552-4450
J9 NAT CHEM BIOL
JI Nat. Chem. Biol.
PD SEP
PY 2012
VL 8
IS 9
BP 741
EP 742
DI 10.1038/nchembio.1049
PG 3
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 996IH
UT WOS:000308077600002
PM 22907089
ER
PT J
AU Yamane, A
Resch, W
Nussezweig, M
Casellas, R
AF Yamane, Arito
Resch, Wolfgang
Nussezweig, Michel
Casellas, Rafael
TI Reassessing genomic targeting of AID Response
SO NATURE IMMUNOLOGY
LA English
DT Letter
ID CLASS-SWITCH RECOMBINATION; RNA-POLYMERASE-II; RECURRENT CHROMOSOMAL
TRANSLOCATIONS; INDUCED CYTIDINE DEAMINASE; B-LYMPHOCYTES; SOMATIC
HYPERMUTATION; SEQUENCING REVEALS; IG GENES; DNA; REGION
C1 [Yamane, Arito; Resch, Wolfgang; Casellas, Rafael] NIAMSD, US NIH, Bethesda, MD 20892 USA.
[Nussezweig, Michel] Rockefeller Univ, Lab Mol Immunol, New York, NY 10021 USA.
[Nussezweig, Michel] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA.
[Casellas, Rafael] NCI, NIH, Bethesda, MD 20892 USA.
RP Yamane, A (reprint author), NIAMSD, US NIH, Bethesda, MD 20892 USA.
EM casellar@mail.nih.gov
RI Yamane, Arito/A-2959-2013
NR 22
TC 1
Z9 1
U1 0
U2 1
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 2012
VL 13
IS 9
BP 798
EP 800
PG 3
WC Immunology
SC Immunology
GA 993MK
UT WOS:000307863600002
ER
PT J
AU Schiemann, J
Schlaudraff, F
Klose, V
Bingmer, M
Seino, S
Magill, PJ
Zaghloul, KA
Schneider, G
Liss, B
Roeper, J
AF Schiemann, Julia
Schlaudraff, Falk
Klose, Verena
Bingmer, Markus
Seino, Susumu
Magill, Peter J.
Zaghloul, Kareem A.
Schneider, Gaby
Liss, Birgit
Roeper, Jochen
TI K-ATP channels in dopamine substantia nigra neurons control bursting and
novelty-induced exploration
SO NATURE NEUROSCIENCE
LA English
DT Article
ID VENTRAL TEGMENTAL AREA; IN-VIVO; PARKINSONS-DISEASE; SPIKE TRAINS;
DORSOMEDIAL STRIATUM; MIDBRAIN NEURONS; FIRING PATTERN; CELLS;
EXPRESSION; RECEPTORS
AB Phasic activation of the dopamine (DA) midbrain system in response to unexpected reward or novelty is critical for adaptive behavioral strategies. This activation of DA midbrain neurons occurs via a synaptically triggered switch from low-frequency background spiking to transient high-frequency burst firing. We found that, in medial DA neurons of the substantia nigra (SN), activity of ATP-sensitive potassium (K-ATP) channels enabled NMDA-mediated bursting in vitro as well as spontaneous in vivo burst firing in anesthetized mice. Cell-selective silencing of K-ATP channel activity in medial SN DA neurons revealed that their K-ATP channel-gated burst firing was crucial for novelty-dependent exploratory behavior. We also detected a transcriptional upregulation of K-ATP channel and NMDA receptor subunits, as well as high in vivo burst firing, in surviving SN DA neurons from Parkinson's disease patients, suggesting that burst-gating K-ATP channel function in DA neurons affects phenotypes in both disease and health.
C1 [Schiemann, Julia; Klose, Verena; Roeper, Jochen] Goethe Univ Frankfurt, Inst Neurophysiol, Neurosci Ctr, Frankfurt, Germany.
[Schlaudraff, Falk; Liss, Birgit] Univ Ulm, Inst Appl Physiol, Ulm, Germany.
[Bingmer, Markus; Schneider, Gaby] Goethe Univ Frankfurt, Dept Comp Sci & Math, Frankfurt, Germany.
[Seino, Susumu] Kobe Univ, Div Cellular & Mol Med, Kobe, Hyogo 657, Japan.
[Magill, Peter J.] Univ Oxford, Dept Pharmacol, MRC, Anat Neuropharmacol Unit, Oxford OX1 3QT, England.
[Magill, Peter J.] Univ Oxford, Oxford Parkinsons Dis Ctr, Oxford, England.
[Zaghloul, Kareem A.] NINDS, Surg Neurol Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Roeper, J (reprint author), Goethe Univ Frankfurt, Inst Neurophysiol, Neurosci Ctr, Frankfurt, Germany.
EM birgit.liss@uni-ulm.de; roeper@em.uni-frankfurt.de
OI Magill, Peter/0000-0001-7141-7071
FU Gemeinnutzige Hertiestiftung; BMBF Nationales Genomforschungsnetzwerk
NGFN-II/plus [01GS08134]; Alfried Krupp prize; LOEWE-Schwerpunkt
Neuronale Koordination Forschungsschwerpunkt Frankfurt NeFF; Bernstein
Fokus Neurotechnology Frankfurt; doctoral fellowship Studienstiftung des
deutschen Volkes; Medical Research Council UK [U138197109]; [SFB815];
[SFB497]
FX We thank S. Petzoldt, H. Schalk and A. Parg for assistance in
immunohistochemistry, and M. Fauler for mRNA expression data analysis.
The study was supported by Gemeinnutzige Hertiestiftung (J.R. and B.
L.), SFB815 (J.R.), SFB497 (B. L.), BMBF Nationales
Genomforschungsnetzwerk NGFN-II/plus (01GS08134, J.R. and B. L.),
Alfried Krupp prize (B. L.), LOEWE-Schwerpunkt Neuronale Koordination
Forschungsschwerpunkt Frankfurt NeFF (J.R. and G. S.), Bernstein Fokus
Neurotechnology Frankfurt (G. S. and M. B.), doctoral fellowship
Studienstiftung des deutschen Volkes (J.S.) and Medical Research Council
UK (U138197109, P.J.M.).
NR 57
TC 65
Z9 69
U1 2
U2 12
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 2012
VL 15
IS 9
BP 1272
EP U141
DI 10.1038/nn.3185
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 996GJ
UT WOS:000308072600018
PM 22902720
ER
PT J
AU Tai, LH
Lee, AM
Benavidez, N
Bonci, A
Wilbrecht, L
AF Tai, Lung-Hao
Lee, A. Moses
Benavidez, Nora
Bonci, Antonello
Wilbrecht, Linda
TI Transient stimulation of distinct subpopulations of striatal neurons
mimics changes in action value
SO NATURE NEUROSCIENCE
LA English
DT Article
ID MEDIUM SPINY NEURONS; BASAL GANGLIA; DECISION-MAKING; DORSOMEDIAL
STRIATUM; SUPERIOR COLLICULUS; MATCHING BEHAVIOR; PREFRONTAL CORTEX;
PRIMATE STRIATUM; TRANSGENIC MICE; MOTOR PROGRAMS
AB In changing environments, animals must adaptively select actions to achieve their goals. In tasks involving goal-directed action selection, striatal neural activity has been shown to represent the value of competing actions. Striatal representations of action value could potentially bias responses toward actions of higher value. However, no study to date has demonstrated the direct effect of distinct striatal pathways in goal-directed action selection. We found that transient optogenetic stimulation of dorsal striatal dopamine D1 and D2 receptor-expressing neurons during decision-making in mice introduced opposing biases in the distribution of choices. The effect of stimulation on choice was dependent on recent reward history and mimicked an additive change in the action value. Although stimulation before and during movement initiation produced a robust bias in choice behavior, this bias was substantially diminished when stimulation was delayed after response initiation. Together, our data suggest that striatal activity is involved in goal-directed action selection.
C1 [Tai, Lung-Hao; Lee, A. Moses; Benavidez, Nora; Wilbrecht, Linda] Ernest Gallo Clin & Res Ctr, Emeryville, CA USA.
[Lee, A. Moses] Univ Calif San Francisco, Neurosci Grad Program, Med Scientist Training Program, San Francisco, CA 94143 USA.
[Benavidez, Nora] Univ Calif Berkeley, Cognit Sci Program, Berkeley, CA 94720 USA.
[Bonci, Antonello; Wilbrecht, Linda] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
[Bonci, Antonello] Natl Inst Drug Abuse, Intramural Program, Baltimore, MD USA.
[Bonci, Antonello] Johns Hopkins Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD USA.
RP Wilbrecht, L (reprint author), Ernest Gallo Clin & Res Ctr, Emeryville, CA USA.
EM lwilbrecht@gallo.ucsf.edu
RI Wilbrecht, Linda/J-7988-2013
FU State of California; US National Institutes of Health [1RC2NS069350,
R01MH087542, R01DA029150]; P. Royer and K. Clayton Family
FX We thank G. Stuber, F. Ambroggi, D. Niell, K. Berger, C. Wu and H.
Peckler for assistance with experiments, V. Kharazia for immunostaining
and histological quantification, K. Deisseroth (Stanford University) for
advice and reagents, and C. Niell for comments on the manuscript. This
work was supported by the State of California, the US National
Institutes of Health (1RC2NS069350; R01MH087542 and R01DA029150), and
the P. Royer and K. Clayton Family.
NR 52
TC 91
Z9 91
U1 2
U2 22
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 2012
VL 15
IS 9
BP 1281
EP U152
DI 10.1038/nn.3188
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 996GJ
UT WOS:000308072600019
PM 22902719
ER
PT J
AU Censor, N
Sagi, D
Cohen, LG
AF Censor, Nitzan
Sagi, Dov
Cohen, Leonardo G.
TI Common mechanisms of human perceptual and motor learning
SO NATURE REVIEWS NEUROSCIENCE
LA English
DT Review
ID PRIMARY VISUAL-CORTEX; TRANSCRANIAL MAGNETIC STIMULATION; CROSS-MODAL
PLASTICITY; MEMORY CONSOLIDATION; TIME-COURSE; TEXTURE-DISCRIMINATION;
INTERMANUAL TRANSFER; REM-SLEEP; DECLARATIVE MEMORY; PROTEIN-SYNTHESIS
AB The adult mammalian brain has a remarkable capacity to learn in both the perceptual and motor domains through the formation and consolidation of memories. Such practice-enabled procedural learning results in perceptual and motor skill improvements. Here, we examine evidence supporting the notion that perceptual and motor learning in humans exhibit analogous properties, including similarities in temporal dynamics and the interactions between primary cortical and higher-order brain areas. These similarities may point to the existence of a common general mechanism for learning in humans.
C1 [Censor, Nitzan; Cohen, Leonardo G.] Natl Inst Neurol Disorders & Stroke, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, Bethesda, MD 20892 USA.
[Sagi, Dov] Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel.
RP Censor, N (reprint author), Natl Inst Neurol Disorders & Stroke, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, Bethesda, MD 20892 USA.
EM censorn@ninds.nih.gov; cohenl@ninds.nih.gov
FU Intramural Research Program of the National Institute of Neurological
Disorders and Stroke (NINDS), US National Institutes of Health; NINDS
Competitive Fellowship
FX We thank E. Dayan for useful suggestions in relation to this manuscript.
This work was supported by the Intramural Research Program of the
National Institute of Neurological Disorders and Stroke (NINDS), US
National Institutes of Health. N.C. was supported by an NINDS
Competitive Fellowship.
NR 129
TC 48
Z9 48
U1 8
U2 85
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-003X
J9 NAT REV NEUROSCI
JI Nat. Rev. Neurosci.
PD SEP
PY 2012
VL 13
IS 9
BP 658
EP 664
DI 10.1038/nrn3315
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 996EM
UT WOS:000308067300013
PM 22903222
ER
PT J
AU Piecha, G
Koleganova, N
Ritz, E
Muller, A
Fedorova, OV
Bagrov, AY
Lutz, D
Schirmacher, P
Gross-Weissmann, ML
AF Piecha, Grzegorz
Koleganova, Nadezda
Ritz, Eberhard
Mueller, Annett
Fedorova, Olga V.
Bagrov, Alexei Y.
Lutz, Diana
Schirmacher, Peter
Gross-Weissmann, Marie-Luise
TI High salt intake causes adverse fetal programming-vascular effects
beyond blood pressure
SO NEPHROLOGY DIALYSIS TRANSPLANTATION
LA English
DT Article
DE blood pressure; fetal programming; nitric oxide; salt; vessel
development
ID SPONTANEOUSLY HYPERTENSIVE-RATS; TO-MESENCHYMAL TRANSITION; CORONARY
HEART-DISEASE; DIETARY SALT; UREMIC CARDIOMYOPATHY; ENDOGENOUS
DIGITALIS; ARTERIAL-PRESSURE; PRENATAL EXPOSURE; DOWN-REGULATION; SODIUM
AB Do detrimental effects on the vasculature of a high dietary sodium intake precede the development of hypertension?.High salt intake causes hypertension, adverse cardiovascular outcomes and potentially also blood pressure (BP)-independent target organ damage. Excess salt intake in pregnancy is known to affect BP in the offspring. The present study was designed to assess whether high salt intake in pregnancy affects BP and vascular morphology in the offspring.
SpragueDawley rats were fed a standard rodent diet with lownormal (0.15) or high (8.0) salt content during pregnancy and lactation. After weaning at 4 weeks of age, offspring were maintained on the same diet or switched to a high- or low-salt diet, respectively. Vascular geometry was assessed in male offspring at 7 and 12 weeks postnatally.
Up to 12 weeks of age, there was no significant difference in telemetrically measured BP between the groups of offspring. At 12 weeks of age, wall thickness of central (aorta, carotid), muscular (mesenteric) and intrapulmonary arteries was significantly higher in offspring of mothers on a high-salt diet irrespective of the post-weaning diet. This correlated with increased fibrosis of the aortic wall, more intense nitrotyrosine staining as well as elevated levels of marinobufagenin (MBG) and asymmetric dimethyl arginine (ADMA).
High salt intake in pregnant rats has long-lasting effects on the modeling of central and muscular arteries in the offspring independent of postnatal salt intake and BP. Circulating MBG and ADMA and local oxidative stress correlate with the adverse vascular modeling.
C1 [Piecha, Grzegorz; Koleganova, Nadezda; Ritz, Eberhard] Univ Heidelberg, Dept Internal Med, D-6900 Heidelberg, Germany.
[Piecha, Grzegorz; Koleganova, Nadezda; Mueller, Annett; Lutz, Diana; Schirmacher, Peter; Gross-Weissmann, Marie-Luise] Univ Heidelberg, Inst Pathol, D-6900 Heidelberg, Germany.
[Piecha, Grzegorz] Med Univ Silesia, Dept Nephrol Endocrinol & Metab Dis, Katowice, Poland.
[Fedorova, Olga V.; Bagrov, Alexei Y.] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA.
RP Piecha, G (reprint author), Univ Heidelberg, Dept Internal Med, D-6900 Heidelberg, Germany.
EM g.piecha@gmx.de
FU Collegium Nephrologicum e.V., Heidelberg; International Society of
Nephrology; Intramural Research Program, National Institute on Aging,
National Institutes of Health
FX The study was supported by Collegium Nephrologicum e.V., Heidelberg.
G.P. and N.K. were supported by fellowships of the International Society
of Nephrology. The work of A.Y.B. and O.V.F. was supported by Intramural
Research Program, National Institute on Aging, National Institutes of
Health.
NR 47
TC 14
Z9 15
U1 0
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0931-0509
J9 NEPHROL DIAL TRANSPL
JI Nephrol. Dial. Transplant.
PD SEP
PY 2012
VL 27
IS 9
BP 3464
EP 3476
DI 10.1093/ndt/gfs027
PG 13
WC Transplantation; Urology & Nephrology
SC Transplantation; Urology & Nephrology
GA 998MS
UT WOS:000308244400017
PM 22431707
ER
PT J
AU Kenna, GA
Swift, RM
Hillemacher, T
Leggio, L
AF Kenna, George A.
Swift, Robert M.
Hillemacher, Thomas
Leggio, Lorenzo
TI The Relationship of Appetitive, Reproductive and Posterior Pituitary
Hormones to Alcoholism and Craving in Humans
SO NEUROPSYCHOLOGY REVIEW
LA English
DT Review
DE Hormones; Neuroendocrinology; Alcohol dependence; Alcoholism;
Appetitive; Pituitary; Genetics
ID ATRIAL-NATRIURETIC-PEPTIDE; PROLACTIN SERUM-LEVELS;
THYROTROPIN-RELEASING-HORMONE; RANDOMIZED CONTROLLED-TRIAL; TERM
ABSTINENT ALCOHOLICS; SOCIAL ANXIETY DISORDER; VENTRAL TEGMENTAL AREA;
BLOOD-GLUCOSE LEVEL; BREAST-CANCER RISK; NUCLEUS-ACCUMBENS
AB A significant challenge for understanding alcoholism lies in discovering why some, but not other individuals, become dependent on alcohol. Genetic, environmental, cultural, developmental, and neurobiological influences are recognized as essential factors underlying a person's risk for becoming alcohol dependent (AD); however, the neurobiological processes that trigger this vulnerability are still poorly understood. Hormones are important in the regulation of many functions and several hormones are strongly associated with alcohol use. While medical consequences are important, the primary focus of this review is on the underlying confluence of appetitive/feeding, reproductive and posterior pituitary hormones associated with distinct phases of alcoholism or assessed by alcohol craving in humans. While these hormones are of diverse origin, the involvement with alcoholism by these hormone systems is unmistakable, and demonstrates the complexity of interactions with alcohol and the difficulty of successfully pursuing effective treatments. Whether alcohol associated changes in the activity of certain hormones are the result of alcohol use or are the result of an underlying predisposition for alcoholism, or a combination of both, is currently of great scientific interest. The evidence we present in this review suggests that appetitive hormones may be markers as they appear involved in alcohol dependence and craving, that reproductive hormones provide an example of the consequences of drinking and are affected by alcohol, and that posterior pituitary hormones have potential for being targets for treatment. A better understanding of the nature of these associations may contribute to diagnosing and more comprehensively treating alcoholism. Pharmacotherapies that take advantage of our new understanding of hormones, their receptors, or their potential relationship to craving may shed light on the treatment of this disorder.
C1 [Kenna, George A.; Swift, Robert M.; Leggio, Lorenzo] Brown Univ, Dept Psychiat & Human Behav, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA.
[Hillemacher, Thomas] Hannover Med Sch, Ctr Addict Res CARe, Dept Psychiat Social Psychiat & Psychotherapy, D-3000 Hannover, Germany.
[Leggio, Lorenzo] NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, Lab Clin & Translat Studies, NIH, Bethesda, MD USA.
[Leggio, Lorenzo] NIDA, Intramural Res Program, NIH, Baltimore, MD USA.
RP Kenna, GA (reprint author), Brown Univ, Dept Psychiat & Human Behav, Ctr Alcohol & Addict Studies, Box G-S121-5, Providence, RI 02912 USA.
EM George_Kenna@Brown.edu
RI Leggio, Lorenzo/M-2972-2016
FU NIAAA NIH HHS [R21 AA019994, R01 AA016079, R03 AA020169, R21 AA019709,
R21 AA021128]
NR 217
TC 16
Z9 16
U1 2
U2 11
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1040-7308
J9 NEUROPSYCHOL REV
JI Neuropsychol. Rev.
PD SEP
PY 2012
VL 22
IS 3
BP 211
EP 228
DI 10.1007/s11065-012-9209-y
PG 18
WC Psychology, Clinical; Neurosciences
SC Psychology; Neurosciences & Neurology
GA 998MU
UT WOS:000308244700001
PM 22772772
ER
PT J
AU Costantine, MM
Clark, EAS
Lai, YL
Rouse, DJ
Spong, CY
Mercer, BM
Sorokin, Y
Thorp, JM
Ramin, SM
Malone, FD
Carpenter, M
Miodovnik, M
O'Sullivan, MJ
Peaceman, AM
Caritis, SN
AF Costantine, Maged M.
Clark, Erin A. S.
Lai, Yinglei
Rouse, Dwight J.
Spong, Catherine Y.
Mercer, Brian M.
Sorokin, Yoram
Thorp, John M.
Ramin, Susan M.
Malone, Fergal D.
Carpenter, Marshall
Miodovnik, Menachem
O'Sullivan, Mary J.
Peaceman, Alan M.
Caritis, Steve N.
CA Eunice Kennedy Shriver Natl Inst
TI Association of Polymorphisms in Neuroprotection and Oxidative Stress
Genes and Neurodevelopmental Outcomes After Preterm Birth
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID CEREBRAL-PALSY; MAGNESIUM-SULFATE; ALTERED EXPRESSION; ANTENATAL
EXPOSURE; RECEPTOR; BRAIN; RISK; MORTALITY; INFANTS; INJURY
AB OBJECTIVE: To estimate the associations between polymorphisms in neuronal homeostasis, neuroprotection, and oxidative stress candidate genes and neurodevelopmental disability.
METHODS: This was a nested case-control analysis of a randomized trial of magnesium sulfate administered to women at imminent risk for early (before 32 weeks) preterm birth for the prevention of death or cerebral palsy in their offspring. We evaluated 21 single-nucleotide polymorphisms (SNPs) in 17 genes associated with neuronal homeostasis, neuroprotection, or oxidative stress in umbilical cord blood. Cases included infant deaths (n = 43) and children with cerebral palsy (n = 24), mental delay (Bayley Mental Developmental Index less than 70; n = 109), or psychomotor delay (Bayley Psychomotor Developmental Index less than 70; n = 91) diagnosed. Controls were race-matched and sex-matched children with normal neurodevelopment. Associations between each SNP and each outcome were assessed in logistic regression models assuming an additive genetic pattern, conditional on maternal race and infant sex, and adjusting for study drug assignment, gestational age at birth, and maternal education.
RESULTS: The odds of cerebral palsy were increased more than 2.5 times for each copy of the minor allele of vasoactive intestinal polypeptipe (VIP, rs17083008) (adjusted odds ratio 2.67, 95% confidence interval 1.09-6.55, P = .03) and 4.5 times for each copy of the minor allele of N-methyl-D-aspartate receptor subunit 3A (GRIN3A, rs3739722) (adjusted odds ratio 4.67, 95% CI 1.36-16.01, P = .01). The association between the advanced glycosylation end product-specific receptor (AGER, rs3134945) SNP and mental delay was modulated by study drug allocation (P = .02).
CONCLUSION: Vasoactive intestinal polypeptipe and GRIN3A SNPs may be associated with cerebral palsy at age 2 in children born preterm. (Obstet Gynecol 2012; 120: 542-50) DOI: http://10.1097/AOG.0b013e318265f232
LEVEL OF EVIDENCE: II
C1 Univ Texas Med Branch, Dept Obstet, Galveston, TX USA.
Univ Texas Med Branch, Dept Gynecol, Galveston, TX USA.
Univ Utah, Salt Lake City, UT USA.
Univ Alabama Birmingham, Birmingham, AL USA.
Case Western Reserve Univ, Metrohlth Med Ctr, Cleveland, OH USA.
Univ Tennessee, Memphis, TN USA.
Wayne State Univ, Detroit, MI USA.
Univ N Carolina, Chapel Hill, NC USA.
Univ Texas Hlth Sci Ctr Houston, Houston, TX USA.
Columbia Univ, New York, NY USA.
Brown Univ, Providence, RI 02912 USA.
Univ Cincinnati, Cincinnati, OH USA.
Univ Miami, Miami, FL USA.
Northwestern Univ, Chicago, IL 60611 USA.
Univ Pittsburgh, Pittsburgh, PA USA.
George Washington Univ, Ctr Biostat, Washington, DC USA.
Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Costantine, MM (reprint author), 301 Univ Blvd, Galveston, TX 77555 USA.
EM mmcostan@utmb.edu
OI caritis, steve/0000-0002-2169-0712; Peaceman, Alan/0000-0002-4515-4850
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) [HD27869, HD34208, HD34116, HD40544, HD27915,
HD34136, HD21414, HD27917, HD27860, HD40560, HD40545, HD40485, HD40500,
HD27905, HD27861, HD34122, HD40512, HD53907, HD34210, HD21410, HD36801,
HD19897, MO1-RR-000080]; National Institute of Neurological Disorders
and Stroke (NINDS)
FX The project described was supported by grants from the Eunice Kennedy
Shriver National Institute of Child Health and Human Development (NICHD)
HD27869, HD34208, HD34116, HD40544, HD27915, HD34136, HD21414, HD27917,
HD27860, HD40560, HD40545, HD40485, HD40500, HD27905, HD27861, HD34122,
HD40512, HD53907, HD34210, HD21410, HD36801, HD19897, MO1-RR-000080, and
by the National Institute of Neurological Disorders and Stroke (NINDS),
and does not necessarily represent the official views of the NICHD,
NINDS, or the National Institutes of Health.
NR 34
TC 3
Z9 3
U1 1
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD SEP
PY 2012
VL 120
IS 3
BP 542
EP 550
DI 10.1097/AOG.0b013e318265f232
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 999EX
UT WOS:000308293300008
PM 22914463
ER
PT J
AU Sprague, BL
Trentham-Dietz, A
Cronin, KA
AF Sprague, Brian L.
Trentham-Dietz, Amy
Cronin, Kathleen A.
TI A Sustained Decline in Postmenopausal Hormone Use Results From the
National Health and Nutrition Examination Survey, 1999-2010
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; BREAST-CANCER INCIDENCE; REPLACEMENT
THERAPY USE; UNITED-STATES; ESTROGEN USE; SCREENING MAMMOGRAPHY;
INITIATIVE WHI; WOMEN; DISEASE; RISK
AB OBJECTIVE: Short-term declines in postmenopausal hormone use were observed after the Women's Health Initiative trial results in 2002. Although concerns about the trial's generalizability have been expressed, long-term trends in hormone use in a nationally representative sample have not been reported. We sought to evaluate national trends in the prevalence of hormone use and to assess variation by type of formulation and patient characteristics.
METHODS: We examined postmenopausal hormone use during 1999-2010 using cross-sectional data from 10,107 women aged 40 years and older in the National Health and Nutrition Examination Survey.
RESULTS: In 1999-2000, the prevalence of oral postmenopausal hormone use was 22.4% (95% confidence interval [CI] 19.0 -25.8) overall, 13.3% (95% CI 11.0-15.5) for estrogen only, and 8.3% (95% CI 6.2-10.4) for estrogen plus progestin. A sharp decline in use of all formulations occurred in 2003-2004, when the overall prevalence decreased to 11.9% (95% CI 9.6-14.2). This decline was initially limited to non-Hispanic whites; use among non-Hispanic blacks and Hispanics did not decline substantially until 2005-2006. Hormone use continued to decline through 2009-2010 across all patient demographic groups, with the current prevalence now at 4.7% (95% CI 3.3-6.1) overall, 2.7% (95% CI 1.9-3.4) for estrogen only, and 1.7% (95% CI 0.7-2.7) for estrogen plus progestin. Patient characteristics currently associated with hormone use include history of hysterectomy, non-Hispanic white race or ethnicity, and income.
CONCLUSION: Postmenopausal hormone use in the United States has declined in a sustained fashion to low levels across a wide variety of patient subgroups. (Obstet Gynecol 2012; 120: 595-603) DOI: http://10.1097/AOG.0b013e318265df42
LEVEL OF EVIDENCE: II
C1 Univ Vermont, Dept Surg, Burlington, VT 05405 USA.
Univ Vermont, Off Hlth Promot Res, Burlington, VT 05405 USA.
Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI USA.
Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA.
NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Sprague, BL (reprint author), 1 S Prospect St,UHC Rm 4425, Burlington, VT 05401 USA.
EM brian.sprague@uvm.edu
FU National Cancer Institute [U01 CA152958]
FX Supported by the National Cancer Institute (U01 CA152958).
NR 43
TC 69
Z9 69
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD SEP
PY 2012
VL 120
IS 3
BP 595
EP 603
DI 10.1097/AOG.0b013e318265df42
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 999EX
UT WOS:000308293300015
PM 22914469
ER
PT J
AU Magnus, MC
Vestrheim, DF
Nystad, W
Haberg, SE
Stigum, H
London, SJ
Bergsaker, MAR
Caugant, DA
Aaberge, IS
Nafstad, P
AF Magnus, Maria C.
Vestrheim, Didrik F.
Nystad, Wenche
Haberg, Siri Eldevik
Stigum, Hein
London, Stephanie J.
Bergsaker, Marianne A. R.
Caugant, Dominique A.
Aaberge, Ingeborg S.
Nafstad, Per
TI Decline in Early Childhood Respiratory Tract Infections in the Norwegian
Mother and Child Cohort Study After Introduction of Pneumococcal
Conjugate Vaccination
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Article
DE pneumococcal conjugate vaccination; lower respiratory tract infections;
acute otitis media; asthma
ID ACUTE OTITIS-MEDIA; COMMUNITY-ACQUIRED PNEUMONIA;
STREPTOCOCCUS-PNEUMONIAE; CONTROLLED-TRIAL; CARE ATTENDANCE; EFFICACY;
IMPACT; SAFETY; PREVENTION; VACCINES
AB Background: The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into the Norwegian Childhood Immunization Program in 2006. A substantial effectiveness of PCV7 immunization against invasive pneumococcal disease has been demonstrated, whereas evidence of its impact on respiratory tract infections are less consistent.
Methods: This study included children participating in the Norwegian Mother and Child Cohort Study, which recruited pregnant women between 1999 and 2008. Maternal report of acute otitis media (AOM), lower respiratory tract infections (LRTIs) and asthma in the child was compared by PCV7 immunization status, as obtained from the Norwegian Immunization Registry. Generalized linear models with the log-link function were used to report adjusted relative risks (RRs) and 95% confidence intervals (CIs).
Results: For children who had received 3 or more PCV7 immunizations by 12 months of age, the adjusted RRs of AOM and LRTIs between 12 and 18 months were 0.86 (95% CI: 0.81, 0.91) and 0.78 (95% CI: 0.70, 0.87) respectively, when compared with nonimmunized children. A reduced risk of AOM, RR 0.92 (95% CI: 0.90, 0.94), and LRTIs, RR 0.75 (95% CI: 0.71, 0.80), between 18 and 36 months of age was also identified among children who had received 3 or more immunizations by 18 months of age. No association was seen between PCV7 immunization and asthma at 36 months of age.
Conclusion: Reduced incidences of AOM and LRTIs before 36 months of age were observed among children immunized with PCV7 through the childhood immunization program.
C1 [Magnus, Maria C.; Nystad, Wenche; Haberg, Siri Eldevik; Stigum, Hein; Nafstad, Per] Norwegian Inst Publ Hlth, Div Epidemiol, Dept Chron Dis, N-0403 Oslo, Norway.
[Vestrheim, Didrik F.; Caugant, Dominique A.; Aaberge, Ingeborg S.] Norwegian Inst Publ Hlth, Div Infect Dis Control, Dept Bacteriol & Immunol, N-0403 Oslo, Norway.
[Stigum, Hein; Nafstad, Per] Univ Oslo, Dept Gen Practice & Community Med, Fac Med, Oslo, Norway.
[London, Stephanie J.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[London, Stephanie J.] NIEHS, Lab Resp Biol, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Bergsaker, Marianne A. R.] Norwegian Inst Publ Hlth, Dept Vaccine, Div Infect Dis Control, Oslo, Norway.
RP Magnus, MC (reprint author), Norwegian Inst Publ Hlth, Div Epidemiol, Dept Chron Dis, POB 4404 Nydalen, N-0403 Oslo, Norway.
EM maria.christine.mag-nus@fhi.no
OI London, Stephanie/0000-0003-4911-5290
FU Norwegian Ministry of Health; Ministry of Education and Research,
NIH/NIEHS [N01-ES-75558]; Division of Intramural Research ZIA
[ES049019]; NIH/NINDS [1 UO1 NS 047537-01]; Norwegian Research
Council/FUGE [151918/S10]
FX The Norwegian Mother and Child Cohort Study is supported by the
Norwegian Ministry of Health and the Ministry of Education and Research,
NIH/NIEHS (contract no N01-ES-75558 and Division of Intramural Research
ZIA ES049019), NIH/NINDS (grant no. 1 UO1 NS 047537-01) and the
Norwegian Research Council/FUGE (grant no. 151918/S10). The authors have
no other funding or conflicts of interest to disclose.
NR 37
TC 12
Z9 33
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0891-3668
EI 1532-0987
J9 PEDIATR INFECT DIS J
JI Pediatr. Infect. Dis. J.
PD SEP
PY 2012
VL 31
IS 9
BP 951
EP 955
DI 10.1097/INF.0b013e31825d2f76
PG 5
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA 997WB
UT WOS:000308197200021
PM 22627867
ER
PT J
AU Knapp, KM
Read, JS
AF Knapp, Katherine M.
Read, Jennifer S.
TI Efavirenz is not a Known Teratogen Reply
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Letter
ID CONGENITAL-ANOMALIES
C1 [Knapp, Katherine M.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
[Read, Jennifer S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS PAMA Branch, NIH, Bethesda, MD USA.
[Read, Jennifer S.] NVPO OASH OS DHHS, Washington, DC USA.
RP Knapp, KM (reprint author), St Jude Childrens Res Hosp, 332 N Lauderdale St, Memphis, TN 38105 USA.
NR 6
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0891-3668
J9 PEDIATR INFECT DIS J
JI Pediatr. Infect. Dis. J.
PD SEP
PY 2012
VL 31
IS 9
BP 1000
EP 1000
PG 1
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA 997WB
UT WOS:000308197200038
ER
PT J
AU Derrien, B
Majeran, W
Effantin, G
Ebenezer, J
Friso, G
van Wijk, KJ
Steven, AC
Maurizi, MR
Vallon, O
AF Derrien, Benoit
Majeran, Wojciech
Effantin, Gregory
Ebenezer, Joseph
Friso, Giulia
van Wijk, Klaas J.
Steven, Alasdair C.
Maurizi, Michael R.
Vallon, Olivier
TI The purification of the Chlamydomonas reinhardtii chloroplast ClpP
complex: additional subunits and structural features
SO PLANT MOLECULAR BIOLOGY
LA English
DT Article
DE Proteolysis; Chloroplast; Oligomeric protein; Negative staining electron
microscopy
ID ATP-DEPENDENT PROTEASE; N-TERMINAL DOMAIN; ESCHERICHIA-COLI; ADAPTER
PROTEIN; FUNCTIONAL IMPLICATIONS; ARABIDOPSIS-THALIANA;
ELECTRON-MICROSCOPY; SUBSTRATE-BINDING; PLANT DEVELOPMENT; DEGRADATION
AB The ClpP peptidase is a major constituent of the proteolytic machinery of bacteria and organelles. The chloroplast ClpP complex is unusual, in that it associates a large number of subunits, one of which (ClpP1) is encoded in the chloroplast, the others in the nucleus. The complexity of these large hetero-oligomeric complexes has been a major difficulty in their overproduction and biochemical characterization. In this paper, we describe the purification of native chloroplast ClpP complex from the green alga Chlamydomonas reinhardtii, using a strain that carries the Strep-tag II at the C-terminus of the ClpP1 subunit. Similar to land plants, the algal complex comprises active and inactive subunits (3 ClpP and 5 ClpR, respectively). Evidence is presented that a sub-complex can be produced by dissociation, comprising ClpP1 and ClpR1, 2, 3 and 4, similar to the ClpR-ring described in land plants. Our Chlamydomonas ClpP preparation also contains two ClpT subunits, ClpT3 and ClpT4, which like the land plant ClpT1 and ClpT2 show 2 Clp-N domains. ClpTs are believed to function in substrate binding and/or assembly of the two heptameric rings. Phylogenetic analysis indicates that ClpT subunits have appeared independently in Chlorophycean algae, in land plants and in dispersed cyanobacterial genomes. Negative staining electron microscopy shows that the Chlamydomonas complex retains the barrel-like shape of homo-oligomeric ClpPs, with 4 additional peripheral masses that we speculate represent either the additional IS1 domain of ClpP1 (a feature unique to algae) or ClpTs or extensions of ClpR subunits.
C1 [Derrien, Benoit; Vallon, Olivier] UPMC, CNRS, Inst Biol Physicochim, UMR7141, F-75005 Paris, France.
[Majeran, Wojciech; Friso, Giulia; van Wijk, Klaas J.] Cornell Univ, Dept Plant Biol, Ithaca, NY 14853 USA.
[Majeran, Wojciech] Univ Paris Diderot, Sorbonne Paris Cite, Inst Sci Vegetal, CNRS,UPR 2355, F-91198 Gif Sur Yvette, France.
[Effantin, Gregory; Steven, Alasdair C.] NIAMS, Struct Biol Res Lab, NIH, Bethesda, MD USA.
[Ebenezer, Joseph; Maurizi, Michael R.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Vallon, O (reprint author), UPMC, CNRS, Inst Biol Physicochim, UMR7141, 13 Rue Pierre & Marie Curie, F-75005 Paris, France.
EM ovallon@ibpc.fr
FU Agence Nationale de la Recherche; CNRS; Universite Pierre et Marie Curie
[UMR 7141]; National Science Foundation [MCB-1021963]; NIAMS; Center for
Cancer Research, NCI
FX We thank Adrain Clarke (Umea University) for providing the ClpP5 and
ClpP6 antibodies and Francis-Andre Wollman for support and advice. This
work was supported in part by the Agence Nationale de la Recherche
(grant Algomics) and by the CNRS and Universite Pierre et Marie Curie,
UMR 7141 (BD, OV), by the National Science Foundation grant MCB-1021963
(WM, GF, KJVW), by the intramural research program of NIAMS (GE, ACS)
and by the intramural program of the Center for Cancer Research, NCI
(EJ, MRM).
NR 61
TC 7
Z9 7
U1 1
U2 17
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0167-4412
J9 PLANT MOL BIOL
JI Plant Mol.Biol.
PD SEP
PY 2012
VL 80
IS 2
BP 189
EP 202
DI 10.1007/s11103-012-9939-5
PG 14
WC Biochemistry & Molecular Biology; Plant Sciences
SC Biochemistry & Molecular Biology; Plant Sciences
GA 994WH
UT WOS:000307964400005
PM 22772861
ER
PT J
AU Kovalchik, SA
Charles-Schoeman, C
Khanna, D
Paulus, HE
AF Kovalchik, Stephanie A.
Charles-Schoeman, Christina
Khanna, Dinesh
Paulus, Harold E.
TI An association study of disease activity score components and patient
satisfaction with overall health for early RA patients on non-biologic
DMARD therapy
SO RHEUMATOLOGY INTERNATIONAL
LA English
DT Article
DE Disease activity score; Disease-modifying antirheumatic drugs;
Remission; Rheumatoid arthritis; Patient-reported outcome; Patient
satisfaction; Stiffness
ID IMPACT MEASUREMENT SCALES; RHEUMATOID-ARTHRITIS; AMERICAN-COLLEGE;
DRUGS; QUESTIONNAIRE; REMISSION; VALIDITY
AB Patient overall satisfaction with health (PSH) was measured by a subset of questions from the Arthritis Impact Measurement Scales II. Based on longitudinal observations for 267 early rheumatoid arthritis (RA) patients of the United States Western Consortium (WC) cohort receiving first non-biologic DMARD treatment, we estimated the 1-year change in PSH ( PSH). Logistic regression analysis was used to estimate the association of improvement in PSH with the core set of clinical and patient-reported components of disease activity scores (DAS). Most patients were more satisfied with health after 1 year of treatment (80%); few achieved DAS28-ESR minimal disease activity (27%) or remission (7%). Laboratory and joint count measures were not associated with improved 12-month PSH. Patients with greater HAQ-DI (P = 0.0473) and self-reported stiffness (P = 0.0669) were more likely to have a perceived overall health benefit from treatment. Regardless of objective disease status, patients are generally satisfied with first-line treatment, which could present a challenge to implementing DAS-guided treatment change. Patients with greater self-reported functional limitations might have lower expectations for treatment benefit and be less willing to modify their current therapy; subjective assessments of function and stiffness could be particularly useful in identifying these patients.
C1 [Kovalchik, Stephanie A.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA.
[Charles-Schoeman, Christina; Khanna, Dinesh; Paulus, Harold E.] Univ Calif Los Angeles, Div Rheumatol, Los Angeles, CA 90095 USA.
RP Kovalchik, SA (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, EPS 8044, Rockville, MD 20892 USA.
EM kovalchiksa@mail.nih.gov
FU National Institutes of Health/National Institute of Allergy and
Infectious Diseases [T32-AI007370]
FX The Western Consortium of Practicing Rheumatologists: J. Javier
Orozco-Alcala, MD (Guadalajara, Mexico); Karen Basin, MD (Medford, OR);
Martin Berry, MD (Bakersfield, CA); Charles Boniske, MD (Visalia, CA);
Melvin Britton, MD (Palo Alto, CA); Ken Bulpitt, MD (Torrance, CA);
Jeffrey Carlin, MD (Seattle, WA); H. Walter Emori, MD (Medford, OR);
Robert Ettlinger, MD (Tacoma, WA); Daniel Furst, MD (Seattle, WA, now in
Los Angeles, CA); Gregory Gardner, MD (Seattle, WA); Robert Gerber, MD
(Medford, OR); Maria Greenwald, MD (Palm Desert, CA); Karen Kolba, MD
(Santa Maria, CA); George Krick, MD (Tacoma, WA); Max Lundberg, MD
(Sandy, UT); Anne MacGuire, MD (Casper, WY); Philip Mease, MD (Seattle,
WA); Ghislaine Bernard Medina, MD (Guadalajara, Mexico); Raymond Mirise,
MD (Los Angeles, CA, now in Glendale, AZ); Ina Oppliger, MD (Seattle,
WA, now in Kansas City, MO); Allen Sawitzke, MD (Salt Lake City, UT);
Gerald Schoepflin, MD (Portland, OR); John Seaman, MD (Seattle, WA, now
in Tacoma, WA); Robert Shapiro, MD (Sacramento, CA); Fredrica Smith, MD
(Los Alamos, CA); Marcia Sparling, MD (Vancouver, WA); Elizabeth
Tindall, MD (Portland, OR); Michael Weisman, MD (San Diego, CA, now in
Los Angeles, CA); Mark Wener, MD (Seattle, WA); Craig Wiesenhutter, MD
(Coeur dAlene, ID); Kenneth Wiesner, MD (Sacramento, CA); Robert
Willkens, MD (Seattle, WA); Kenneth Wilske, MD (Seattle, WA); Andrew
Wong, MD (Northridge, CA); George Young, MD (Boulder, CO). Thank you to
Paul Maranian for his assistance with the data analysis. This research
was supported by a National Institutes of Health/National Institute of
Allergy and Infectious Diseases training grant T32-AI007370.
NR 15
TC 3
Z9 3
U1 0
U2 1
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0172-8172
J9 RHEUMATOL INT
JI Rheumatol. Int.
PD SEP
PY 2012
VL 32
IS 9
BP 2725
EP 2729
DI 10.1007/s00296-011-2037-1
PG 5
WC Rheumatology
SC Rheumatology
GA 996RL
UT WOS:000308111400020
PM 21805175
ER
PT J
AU Xiong, Y
Zhou, ZH
Notkins, AL
AF Xiong, Y.
Zhou, Z. -H.
Notkins, A. L.
TI Pictorial Demonstration of the Simultaneous Binding of Multiple
Unrelated Antigens to Individual Polyreactive Antibody-Producing B Cells
SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY
LA English
DT Letter
ID MONOCLONAL AUTOANTIBODIES; REPERTOIRE; ORGANS; REACT
C1 [Xiong, Y.; Notkins, A. L.] Natl Inst Dent & Craniofacial Res, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA.
[Zhou, Z. -H.] US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA.
RP Notkins, AL (reprint author), Natl Inst Dent & Craniofacial Res, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA.
EM anotkins@mail.nih.gov
FU Intramural NIH HHS [ZIA DE000423-25]
NR 7
TC 0
Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0300-9475
J9 SCAND J IMMUNOL
JI Scand. J. Immunol.
PD SEP
PY 2012
VL 76
IS 3
BP 342
EP 343
DI 10.1111/j.1365-3083.2012.02746.x
PG 2
WC Immunology
SC Immunology
GA 996MV
UT WOS:000308094200018
PM 22703112
ER
PT J
AU Yang, S
Zhao, YC
AF Yang, Song
Zhao, Yichuan
TI Checking the Short-Term and Long-Term Hazard Ratio Model for Survival
Data
SO SCANDINAVIAN JOURNAL OF STATISTICS
LA English
DT Article
DE censoring; goodness of fit; martingale residuals; model checking;
omnibus test; survival data
ID MAXIMUM-LIKELIHOOD-ESTIMATION; MARTINGALE-BASED RESIDUALS; ESTROGEN PLUS
PROGESTIN; CENSORED-DATA; SEMIPARAMETRIC ANALYSIS; TRANSFORMATION
MODELS; REGRESSION-MODELS; THERAPY; DISEASE; TRIAL
AB . The short-term and long-term hazard ratio model includes the proportional hazards model and the proportional odds model as submodels, and allows a wider range of hazard ratio patterns compared with some of the more traditional models. We propose two omnibus tests for checking this model, based, respectively, on the martingale residuals and the contrast between the non-parametric and model-based estimators of the survival function. These tests are shown to be consistent against any departure from the model. The empirical behaviours of the tests are studied in simulations, and the tests are illustrated with some real data examples.
C1 [Yang, Song] NHLBI, Off Biostat Res, Div Cardiovasc Sci, NIH,DHHS, Bethesda, MD 20892 USA.
[Zhao, Yichuan] Georgia State Univ, Dept Math & Stat, Atlanta, GA 30303 USA.
RP Yang, S (reprint author), NHLBI, Off Biostat Res, Div Cardiovasc Sci, NIH,DHHS, 6701 Rockledge Dr,MSC 7913, Bethesda, MD 20892 USA.
EM yangso@nhlbi.nih.gov
FU NSA [H98230-12-1-0209]
FX The authors thank the editors and reviewers for their constructive
comments and suggestions that have led to an improved manuscript. The
research of Yichuan Zhao was partially supported by NSA grant
#H98230-12-1-0209.
NR 22
TC 1
Z9 1
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0303-6898
EI 1467-9469
J9 SCAND J STAT
JI Scand. J. Stat.
PD SEP
PY 2012
VL 39
IS 3
BP 554
EP 567
DI 10.1111/j.1467-9469.2012.00804.x
PG 14
WC Statistics & Probability
SC Mathematics
GA 996NF
UT WOS:000308095500010
ER
PT J
AU Mercado-Feliciano, M
Cora, MC
Witt, KL
Granville, CA
Hejtmancik, MR
Fomby, L
Knostman, KA
Ryan, MJ
Newbold, R
Smith, C
Foster, PM
Vallant, MK
Stout, MD
AF Mercado-Feliciano, Minerva
Cora, Michelle C.
Witt, Kristine L.
Granville, Courtney A.
Hejtmancik, Milton R.
Fomby, Laurene
Knostman, Katherine A.
Ryan, Michael J.
Newbold, Retha
Smith, Cynthia
Foster, Paul M.
Vallant, Molly K.
Stout, Matthew D.
TI An ethanolic extract of black cohosh causes hematological changes but
not estrogenic effects in female rodents
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE Black cohosh; Actaea racemosa; Non-regenerative macrocytic anemia;
Micronucleus; Genetic toxicity
ID MACROCYTIC-MEGALOBLASTIC ANEMIA; CIMICIFUGA-RACEMOSA EXTRACT; MALE
B6C3F1 MICE; PERIPHERAL-BLOOD; DIRECT GAVAGE; DAMAGE; 1,3-BUTADIENE;
RECEPTOR; ASSAY; DIDEOXYINOSINE
AB Black cohosh rhizome (Actaea racemosa) is used as a remedy for pain and gynecological ailments; modern preparations are commonly sold as ethanolic extracts available as dietary supplements. Black cohosh was nominated to the National Toxicology Program (NTP) for toxicity testing due to its widespread use and lack of safety data. Several commercially available black cohosh extracts (BCE) were characterized by the NIP, and one with chemical composition closest to formulations available to consumers was used for all studies. Female B6C3F1/N mice and Wistar Han rats were given 0, 15 (rats only), 62.5 (mice only). 125, 250, 500, or 1000 mg/kg/day BCE by gavage for 90 days starting at weaning. BCE induced dose-dependent hematological changes consistent with a non-regenerative macrocytic anemia and increased frequencies of peripheral micronucleated red blood cells (RBC) in both species. Effects were more severe in mice, which had decreased RBC counts in all treatment groups and increased micronucleated RBC at doses above 125 mg/kg. Dosedependent thymus and liver toxicity was observed in rats but not mice. No biologically significant effects were observed in other organs. Puberty was delayed 2.9 days at the highest treatment dose in rats; a similar magnitude delay in mice occurred in the 125 and 250 mg/kg groups but not at the higher doses. An additional uterotrophic assay conducted in mice exposed for 3 days to 0.001, 0.01, 0.1, 1, 10, 100 and 500 mg/kg found no estrogenic or anti-estrogenic activity. These are the first studies to observe adverse effects of BCE in rodents. (c) 2012 Elsevier Inc. All rights reserved.
C1 [Mercado-Feliciano, Minerva; Cora, Michelle C.; Witt, Kristine L.; Newbold, Retha; Smith, Cynthia; Foster, Paul M.; Vallant, Molly K.; Stout, Matthew D.] NIEHS, Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA.
[Granville, Courtney A.; Hejtmancik, Milton R.; Fomby, Laurene; Knostman, Katherine A.; Ryan, Michael J.] Battelle Mem Inst, Columbus, OH 43201 USA.
RP Stout, MD (reprint author), NIEHS, Natl Toxicol Program, NIH, 111 Alexander Dr,Mail Drop K2-06, Res Triangle Pk, NC 27709 USA.
EM StoutM@niehs.nih.gov
FU Intramural NIH HHS [Z99 ES999999]; NIEHS NIH HHS [N01ES35514,
N01ES55536, N01ES55551, Z01 ES045004]; PHS HHS [1 Z01 ESO45004-11]
NR 48
TC 5
Z9 5
U1 3
U2 14
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 2012
VL 263
IS 2
BP 138
EP 147
DI 10.1016/j.taap.2012.05.022
PG 10
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 996BH
UT WOS:000308058500002
PM 22687605
ER
PT J
AU Wise-Draper, TM
Draper, DJ
Gutkind, JS
Molinolo, AA
Wikenheiser-Brokamp, KA
Wells, SI
AF Wise-Draper, Trisha M.
Draper, David J.
Gutkind, J. Silvio
Molinolo, Alfredo A.
Wikenheiser-Brokamp, Kathryn A.
Wells, Susanne I.
TI Future directions and treatment strategies for head and neck squamous
cell carcinomas
SO TRANSLATIONAL RESEARCH
LA English
DT Article
ID PHASE-II TRIAL; RISK HUMAN-PAPILLOMAVIRUS; DEK ONCOGENE; ONCOLOGY-GROUP;
STEM-CELLS; ONCOLYTIC ADENOVIRUS; RANDOMIZED-TRIAL; BLADDER-CANCER;
BREAST-CANCER; ORAL-CANCER
AB Head and neck cancer is a devastating disease that afflicts many individuals worldwide. Conventional therapies are successful in only a limited subgroup and often leave the patient with disfigurement and long lasting adverse effects on normal physiologic functions. The field is in dire need of new therapies. Oncolytic viral as well as targeted therapies have shown some success in other malignancies and are attractive for the treatment of head and neck cancer. Recently, it has been shown that a subset of head and neck cancers is human papillomavirus (HPV) positive and that this subset of cancers is biologically distinct and more sensitive to chemoradiation therapies although the underlying mechanism is unclear. However, chemoresistance remains a general problem. One candidate mediator of therapeutic response, which is of interest for the targeting of both HPV-positive and -negative tumors is the human DEK proto-oncogene. DEK is upregulated in numerous tumors including head and neck cancers regardless of their HPV status. Depletion of DEK in tumor cells in culture results in sensitivity to genotoxic agents, particularly in rapidly proliferating cells. This suggests that tumors with high DEK protein expression may be correlated with poor clinical response to clastogenic therapies. Targeting molecules such as DEK in combination with new and/or conventional therapies, holds promise for novel future therapeutics for head and neck cancer. (Translational Research 2012;160:167-177)
C1 Cincinnati Childrens Hosp Med Ctr, Div Hematol & Oncol, Cincinnati, OH USA.
Univ Cincinnati, Univ Hosp, Div Internal Med, Cincinnati, OH 45267 USA.
Good Samaritan Hosp, TriHlth Canc Inst, Div Hematol & Oncol, Cincinnati, OH USA.
Natl Inst Dent Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
Cincinnati Childrens Hosp Med Ctr, Div Pathol & Lab Med, Cincinnati, OH USA.
Cincinnati Childrens Hosp Med Ctr, Div Pulm Biol, Cincinnati, OH USA.
RP Wise-Draper, TM (reprint author), Univ Cincinnati, Dept Internal Med, 231 Albert Sabin Way,ML 0557, Cincinnati, OH 45267 USA.
EM wiseth@uc.edu
OI Wise-Draper, Trisha/0000-0002-7279-4028
FU University of Cincinnati; Public Health Service from the NIH [RO1
CA116316]; NIDCR, NIH
FX Supported by the Clinical Scientist Training Program at the University
of Cincinnati (T.M.W.-D.), by Public Health Service grant, RO1 CA116316,
from the NIH (S.I.W.); and by the Intramural Research Program, NIDCR,
NIH (J.S.G. A.A.M.).
NR 83
TC 13
Z9 13
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1931-5244
J9 TRANSL RES
JI Transl. Res.
PD SEP
PY 2012
VL 160
IS 3
BP 167
EP 177
DI 10.1016/j.trsl.2012.02.002
PG 11
WC Medical Laboratory Technology; Medicine, General & Internal; Medicine,
Research & Experimental
SC Medical Laboratory Technology; General & Internal Medicine; Research &
Experimental Medicine
GA 998VR
UT WOS:000308269000001
PM 22683420
ER
PT J
AU Lozier, JN
Cullinane, AM
Nghiem, K
Chang, R
Horne, MK
AF Lozier, Jay N.
Cullinane, Ann M.
Nghiem, Khanh
Chang, Richard
Horne, McDonald K., III
TI Biochemical dynamics relevant to the safety of low-dose, intraclot
alteplase for deep vein thrombosis
SO TRANSLATIONAL RESEARCH
LA English
DT Article
ID TISSUE-PLASMINOGEN-ACTIVATOR; VENOUS THROMBOSIS; THROMBOLYSIS; CATHETER;
FIBRIN; PAI-1
AB Intraclot tissue plasminogen activator (tPA) has been shown to be an effective treatment for deep vein thrombosis (DVT) (Radiology 2008;246:619 and J Vasc Interv Radio! 2011;22:1107). We sought to correlate pharmacokinetics of tPA, fibrinogen, fibrinolytic inhibitors, and D-dimers with the safety and efficacy of intraclot tPA. Thirty subjects received intraclot tPA for lower extremity DVT by infiltrating the thrombus with <= 10 mg doses tPA in an open-label study, using a pulse-spray catheter. We measured various parameters over 8 h following a first dose of tPA. Mean tPA levels of 75 units per mL (95% confidence interval 19-131 units/mL) were seen immediately after administration of a mean tPA dose of 8.0 mg (SD 1.5 mg). tPA levels returned to baseline within 2 h of completion of treatment. Plasminogen activator inhibitor-1 (PAI-1) was consumed following tPA treatment, but rose to levels significantly greater than baseline (P < 0.001). Fibrinogen decreased slightly, but remained >125 mg/dL for all subjects. alpha 2-antiplasmin decreased from a mean of 115 units/mL to 56 units/mL after tPA administration (P < 0.001) and remained decreased for 8 h. Plasminogen at baseline (112 units/mL) decreased to 89 units/mL immediately after tPA administration (P < 0.001) and was unchanged thereafter. D-dimer levels were >20 mu g/mL in all but 4 subjects, one of whom was the only one to fail to achieve clot lysis. The safety of low-dose, intraclot tPA is due to its short persistence in the circulation, lack of hypofibrinogenemia, and a reflexive rise of PAI-1. Subjects whose D-dimers remain <20 mu g/mL are at risk of not achieving thrombolysis. (Translational Research 2012;160:217-222)
C1 [Lozier, Jay N.] NIH, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA.
NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
RP Lozier, JN (reprint author), NIH, Ctr Clin, Dept Lab Med, Bldg 10,Room 2C306,MSC 1508, Bethesda, MD 20892 USA.
EM lozierjn@cc.nih.gov
FU National Institutes of Health Clinical Center
FX Supported by the National Institutes of Health Clinical Center.
NR 16
TC 2
Z9 2
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1931-5244
J9 TRANSL RES
JI Transl. Res.
PD SEP
PY 2012
VL 160
IS 3
BP 217
EP 222
DI 10.1016/j.trsl.2012.01.025
PG 6
WC Medical Laboratory Technology; Medicine, General & Internal; Medicine,
Research & Experimental
SC Medical Laboratory Technology; General & Internal Medicine; Research &
Experimental Medicine
GA 998VR
UT WOS:000308269000005
PM 22683421
ER
PT J
AU Aldstadt, J
Yoon, IK
Tannitisupawong, D
Jarman, RG
Thomas, SJ
Gibbons, RV
Uppapong, A
Iamsirithaworn, S
Rothman, AL
Scott, TW
Endy, T
AF Aldstadt, Jared
Yoon, In-Kyu
Tannitisupawong, Darunee
Jarman, Richard G.
Thomas, Stephen J.
Gibbons, Robert V.
Uppapong, Angkana
Iamsirithaworn, Sopon
Rothman, Alan L.
Scott, Thomas W.
Endy, Timothy
TI Space-time analysis of hospitalised dengue patients in rural Thailand
reveals important temporal intervals in the pattern of dengue virus
transmission
SO TROPICAL MEDICINE & INTERNATIONAL HEALTH
LA English
DT Article
DE dengue; transmission; serial interval; space-time; clustering; Thailand
ID AEDES-AEGYPTI DIPTERA; PUERTO-RICO; HAEMORRHAGIC FEVER;
INFECTIOUS-DISEASE; CULICIDAE; VIREMIA; BLOOD; TEMPERATURE; ENVIRONMENT;
POPULATION
AB Objective To determine the temporal intervals at which spatial clustering of dengue hospitalisations occurs. Methods Space-time analysis of 262 people hospitalised and serologically confirmed with dengue virus infections in Kamphaeng Phet, Thailand was performed. The cases were observed between 1 January 2009 and 6 May 2011. Spatial coordinates of each patients home were captured using the Global Positioning System. A novel method based on the Knox test was used to determine the temporal intervals between cases at which spatial clustering occurred. These intervals are indicative of the length of time between successive illnesses in the chain of dengue virus transmission. Results The strongest spatial clustering occurred at the 1517-day interval. There was also significant spatial clustering over short intervals (25 days). The highest excess risk was observed within 200 m of a previous hospitalised case and significantly elevated risk persisted within this distance for 3234 days. Conclusions Fifteen to seventeen days are the most likely serial interval between successive dengue illnesses. This novel method relies only on passively detected, hospitalised case data with household locations and provides a useful tool for understanding region-specific and outbreak-specific dengue virus transmission dynamics.
C1 [Aldstadt, Jared] SUNY Buffalo, Dept Geog, Buffalo, NY 14260 USA.
[Yoon, In-Kyu; Tannitisupawong, Darunee; Gibbons, Robert V.] Armed Forces Res Inst Med Sci, Dept Virol, Bangkok 10400, Thailand.
[Jarman, Richard G.; Thomas, Stephen J.] Walter Reed Army Inst Res, Viral Dis Branch, Silver Spring, MD USA.
[Uppapong, Angkana] Kamphaeng Phet Prov Hosp, Dept Pediat, Minist Publ Hlth, Kamphaeng Phet, Thailand.
[Iamsirithaworn, Sopon] Minist Publ Hlth, Bur Epidemiol, Nonthaburi, Thailand.
[Rothman, Alan L.] Univ Rhode Isl, Inst Immunol & Informat, Providence, RI 02908 USA.
[Scott, Thomas W.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA.
[Scott, Thomas W.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Endy, Timothy] SUNY Syracuse, Dept Infect Dis, Syracuse, NY USA.
RP Aldstadt, J (reprint author), SUNY Buffalo, Dept Geog, Buffalo, NY 14260 USA.
EM geojared@buffalo.edu
RI Aldstadt, Jared/A-8508-2009
OI Aldstadt, Jared/0000-0001-9162-7439
FU National Institutes of Health [R01 GM083224, P01 AI034533]; U.S.
Military Infectious Diseases Research Programme
FX This research would not have been possible without the cooperation of
the administration and staff of the Kamphaeng Phet Provincial Hospital,
especially Dr. Kamchai Rungsimunpaiboon, Hospital Director. We would
like to acknowledge the efforts of Ms. Wilaiwan Sridadeth, Ms. Rattiya
Wannawong and the staff of the Kamphaeng Phet-AFRIMS Virology Research
Unit for their thorough fieldwork and careful data management. This
research was funded by National Institutes of Health grants R01 GM083224
and P01 AI034533 and U.S. Military Infectious Diseases Research
Programme. This research benefitted from discussions with working group
members in the Research and Policy for Infectious Disease Dynamics
(RAPIDD) programme of the Science and Technology Directorate, Department
of Homeland Security, and the Fogarty International Center, National
Institutes of Health. The opinions or assertions contained herein are
the private views of the authors and are not to be construed as
reflecting the official views of the National Institutes of Health, the
United States Army or the United States Department of Defense.
NR 55
TC 14
Z9 14
U1 0
U2 14
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 2012
VL 17
IS 9
BP 1076
EP 1085
DI 10.1111/j.1365-3156.2012.03040.x
PG 10
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 994OQ
UT WOS:000307940800006
PM 22808917
ER
PT J
AU Houlden, H
Singleton, AB
AF Houlden, Henry
Singleton, Andrew B.
TI The genetics and neuropathology of Parkinson's disease
SO ACTA NEUROPATHOLOGICA
LA English
DT Review
DE Parkinson's disease; Genetics; Pathology; Synuclein; LRRK2; PARK2;
PARK6; PARK7
ID EARLY-ONSET PARKINSONISM; RECESSIVE JUVENILE PARKINSONISM;
AUTOSOMAL-DOMINANT PARKINSONISM; HEREDITARY SPASTIC PARAPLEGIA;
SPINOCEREBELLAR ATAXIA TYPE-3; HALLERVORDEN-SPATZ-SYNDROME; BRAIN IRON
ACCUMULATION; MULTIPLE SYSTEM ATROPHY; GENOME-WIDE ASSOCIATION;
MACHADO-JOSEPH-DISEASE
AB There has been tremendous progress toward understanding the genetic basis of Parkinson's disease and related movement disorders. We summarize the genetic, clinical and pathological findings of autosomal dominant disease linked to mutations in SNCA, LRRK2, ATXN2, ATXN3, MAPT, GCH1, DCTN1 and VPS35. We then discuss the identification of mutations in PARK2, PARK7, PINK1, ATP13A2, FBXO7, PANK2 and PLA2G6 genes. In particular we discuss the clinical and pathological characterization of these forms of disease, where neuropathology has been important in the likely coalescence of pathways highly relevant to typical PD. In addition to the identification of the causes of monogenic forms of PD, significant progress has been made in defining genetic risk loci for PD; we discuss these here, including both risk variants at LRRK2 and GBA, in addition to discussing the results of recent genome-wide association studies and their implications for PD. Finally, we discuss the likely path of genetic discovery in PD over the coming period and the implications of these findings from a clinical and etiological perspective.
C1 [Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Houlden, Henry] UCL, Mol Neurosci Dept, UCL Inst Neurol, London, England.
[Houlden, Henry] UCL, Natl Hosp Neurol & Neurosurg, London, England.
RP Singleton, AB (reprint author), NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
EM singleta@mail.nih.gov
RI Houlden, Henry/C-1532-2008; Singleton, Andrew/C-3010-2009
OI Houlden, Henry/0000-0002-2866-7777;
FU National Institute on Aging, National Institutes of Health, Department
of Health and Human Services [Z01 AG000957-08, AG000958-08]
FX This work was supported in part by the Intramural Research Program of
the National Institute on Aging, National Institutes of Health,
Department of Health and Human Services; projects number Z01 AG000957-08
and AG000958-08. We are also grateful to the Medical Research Council
(MRC), NORD, the Parkinson's Disease Foundation (PDF), the DMRF and The
Wellcome Trust.
NR 139
TC 101
Z9 105
U1 1
U2 63
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0001-6322
J9 ACTA NEUROPATHOL
JI Acta Neuropathol.
PD SEP
PY 2012
VL 124
IS 3
BP 325
EP 338
DI 10.1007/s00401-012-1013-5
PG 14
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 992EA
UT WOS:000307757200003
PM 22806825
ER
PT J
AU Boyd, SJ
Fang, LJ
Medoff, DR
Dixon, LB
Gorelick, DA
AF Boyd, Susan J.
Fang, Li Juan
Medoff, Deborah R.
Dixon, Lisa B.
Gorelick, David A.
TI Use of a microecological technique' to study crime incidents around
methadone maintenance treatment centers
SO ADDICTION
LA English
DT Article
DE Crime; geocoding; methadone maintenance; neighborhood; spatial analysis
ID SPATIAL-ANALYSIS
AB Aims Concern about crime is a significant barrier to the establishment of methadone treatment centers (MTCs). Methadone maintenance reduces crime among those treated, but the relationship between MTCs and neighborhood crime is unknown. We evaluated crime around MTCs. Setting Baltimore City, MD, USA. Participants We evaluated crime around 13 MTCs and three types of control locations: 13 convenience stores (stores), 13 residential points and 10 general medical hospitals. Measures We collected reports of Part 1 crimes from 1 January 1999 to 31 December 2001 from the Baltimore City Police Department. Design Crimes and residential point locations were mapped electronically by street address (geocoded), and MTCs, hospitals and stores were mapped by visiting the sites with a global positioning satellite (GPS) locator. Concentric circular buffers were drawn at 25-m intervals up to 300 m around each site. We used Poisson regression to assess the relationship between crime counts (incidents per unit area) and distance from the site. Findings There was no significant geographic relationship between crime counts and MTCs or hospitals. A significant negative relationship (parameter estimate -0.3127, P < 0.04) existed around stores in the daytime (7 am7 pm), indicating higher crime counts closer to the stores. We found a significant positive relationship around residential points during daytime (0.5180, P < 0.0001) and at night (0.3303, P < 0.0001), indicating higher crime counts further away. Conclusions Methadone treatment centers, in contrast to convenience stores, are not associated geographically with crime.
C1 [Boyd, Susan J.] Univ Maryland, Dept Psychiat, Sch Med, Baltimore VAMC, Baltimore, MD 21201 USA.
[Fang, Li Juan; Medoff, Deborah R.; Dixon, Lisa B.] Univ Maryland, Dept Psychiat, Sch Med, Div Res Serv, Baltimore, MD 21201 USA.
[Gorelick, David A.] Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD USA.
RP Boyd, SJ (reprint author), Univ Maryland, Dept Psychiat, Sch Med, Baltimore VAMC, 10 N Greene St, Baltimore, MD 21201 USA.
EM susan.boyd@va.gov
FU Substance Abuse Policy Research Program; Robert Wood Johnson Foundation;
Center for Substance Abuse Treatment/Substance Abuse and Mental Health
Services Administration; National Institutes of Health/National
Institute on Drug Abuse
FX This work was supported by the Substance Abuse Policy Research Program,
Robert Wood Johnson Foundation, the Center for Substance Abuse
Treatment/Substance Abuse and Mental Health Services Administration and
the Intramural Research Program of the National Institutes of
Health/National Institute on Drug Abuse.
NR 33
TC 6
Z9 6
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0965-2140
J9 ADDICTION
JI Addiction
PD SEP
PY 2012
VL 107
IS 9
BP 1632
EP 1638
DI 10.1111/j.1360-0443.2012.03872.x
PG 7
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 982MG
UT WOS:000307047800019
PM 22385066
ER
PT J
AU Warden, D
Subramaniam, GA
Carmody, T
Woody, GE
Minhajuddin, A
Poole, SA
Potter, J
Fishman, M
Bogenschutz, M
Patkar, A
Trivedi, MH
AF Warden, Diane
Subramaniam, Geetha A.
Carmody, Thomas
Woody, George E.
Minhajuddin, Abu
Poole, Sabrina A.
Potter, Jennifer
Fishman, Marc
Bogenschutz, Michael
Patkar, Ashwin
Trivedi, Madhukar H.
TI Predictors of attrition with buprenorphine/naloxone treatment in opioid
dependent youth
SO ADDICTIVE BEHAVIORS
LA English
DT Article
DE Retention; Adherence; Opioid dependence; Youth; Adolescents;
Buprenorphine
ID RANDOMIZED CONTROLLED-TRIAL; METHADONE-MAINTENANCE; DRUG-USERS;
TREATMENT RETENTION; SYSTEMATIC REVIEWS; TREATMENT OUTCOMES; TREATMENT
PROGRAM; SUBSTANCE USE; PRIMARY-CARE; ADOLESCENTS
AB Background: In opioid dependent youth there is substantial attrition from medication-assisted treatment. If youth at risk for attrition can be identified at treatment entry or early in treatment, they can be targeted for interventions to help retain them in treatment.
Methods: Opioid dependent adolescents and young adults (n = 152), aged 15-21, were randomized to 12 weeks (BUP, n = 74) or 2 weeks of detoxification (DETOX, n = 78) with buprenorphine/naloxone (Bup/Nal), both in combination with 12 weeks of psychosocial treatment Baseline and early treatment related predictors of treatment attrition were identified in each group using bivariate and multivariate logistic regression.
Results: In the DETOX group 36% left between weeks 2 and 4, at the end of the dose taper, while in the BUP group only 8% left by week 4. In the BUP group, early adherence to Bup/Nal, early opioid negative urines, use of any medications in the month prior to treatment entry, and lifetime non-heroin opioid use were associated with retention while prior 30-day hallucinogen use was associated with attrition. In the DETOX group, only use of sleep medications was associated with retention although not an independent predictor. A broad range of other pre-treatment characteristics was unrelated to attrition.
Conclusions: Prompt attention to those with early non-adherence to medication or an early opioid positive urine, markers available in the first 2 weeks of treatment, may improve treatment retention. Extended Bup/Nal treatment appeared effective in improving treatment retention for youth with opioid dependence across a wide range of demographics, and pre-treatment clinical characteristics. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Warden, Diane; Carmody, Thomas; Trivedi, Madhukar H.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA.
[Subramaniam, Geetha A.] Natl Inst Drug Abuse, Div Neurosci & Behav Res, Bethesda, MD 20892 USA.
[Woody, George E.; Poole, Sabrina A.] Univ Penn, Dept Psychiat, Philadelphia, PA 19106 USA.
[Woody, George E.; Poole, Sabrina A.] Treatment Res Inst, Philadelphia, PA 19106 USA.
[Minhajuddin, Abu] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA.
[Potter, Jennifer] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat MC7733, San Antonio, TX 78229 USA.
[Fishman, Marc] Mt Manor Treatment Ctr, Baltimore, MD 21229 USA.
[Fishman, Marc] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA.
[Bogenschutz, Michael] Univ New Mexico, Ctr Alcoholism Subst Abuse & Addict, Albuquerque, NM 87106 USA.
[Patkar, Ashwin] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27705 USA.
RP Warden, D (reprint author), Univ Texas SW Med Ctr Dallas, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM Diane.Warden@UTSouthwestern.edu
RI Trivedi, Madhukar/A-9029-2013; Potter, Jennifer/C-6720-2008;
OI Potter, Jennifer/0000-0002-7250-4422; Bogenschutz,
Michael/0000-0003-4530-3470
FU National Institutes on Drug Abuse [U10-DA020024, K12-DA000357,
U10-DA13043, KO5 DA-17009]; National Alliance for Research on
Schizophrenia and Depression; NIH (NIDA/NIAAA); Duke Endowment;
AstraZeneca; Forest Pharmaceuticals; Cephalon; Janssen; Jazz; McNeil;
Organon; Orphan; Merck; Lundbeck; Pfizer; Titan; Shire; Sunovion
FX This study was supported by the following grants from the National
Institutes on Drug Abuse: U10-DA020024 (Trivedi) to the University of
Texas Southwestern Medical Center at Dallas, K12-DA000357 (Subramaniam)
to Johns Hopkins University, and U10-DA13043 and KO5 DA-17009 (Woody) to
the University of Pennsylvania. The content is solely the responsibility
of the authors and does not necessarily represent the official views of
the National Institute on Drug Abuse or the National Institutes of
Health.; Dr. Warden previously held stock in Pfizer and Bristol-Myers
Squibb. She has received funding from the National Alliance for Research
on Schizophrenia and Depression. Dr. Woody has served on the advisory
board of the Researched Abuse, Diversion, and Addiction-Related
Surveillance (RADARS) System. Dr. Fishman is the medical director of
Mountain Manor Treatment Center (MMTC), one of multiple research sites
in this study. He is a beneficiary of the trust that owns MMTC and
serves on the governing board of the trust and the board of directors of
MMTC. The terms of Dr. Fishman's potential conflict of interest in
research are managed by Johns Hopkins University in accordance with its
conflicts of interest policies. Dr. Patkar has received research support
from NIH (NIDA/NIAAA), Duke Endowment, AstraZeneca, Forest
Pharmaceuticals, Cephalon, Janssen, Jazz, McNeil, Organon, Orphan,
Merck, Lundbeck, Pfizer, Titan, Shire, Sunovion: has been a
consultant/Advisory Board member of Forest Pharmaceuticals, Gilead. Dey
Pharmaceuticals. Titan, Reckitt Benckiser, and on Speakers Bureau of
Alkermes, Bristol-Myers Squibb, Dey Pharmaceuticals, and Sunovion. Dr.
Trivedi is a consultant to or on speaker bureaus for Alkermes,
AstraZeneca, Axon Advisors, Bristol-Myers Squibb Company, Cephalon, Inc,
Eli Lilly & Company, Evotec, Forest Pharmaceuticals, GlaxoSmithiGine,
Johnson & Johnson PRD, Lundbeck, MedAvante, Neuronetics, Otsuka
Pharmaceuticals, Pamlab, Pfizer Inc., PGxHealth, Rexahn Pharmaceuticals,
SHIRE Development, Takeda, Tal Medical/Purtech Venture, Targacept, and
Transcept. He receives research support from the Agency for Healthcare
Research and Quality (AHRQ), National Institute of Mental Health,
National Institute on Drug Abuse, Naurex, Targacept, and Valient. Drs.
Subramaniam, Carmody, Minhajuddin, and Potter, and Ms. Poole report no
biomedical financial interests or potential conflicts of interest.
NR 52
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U1 5
U2 22
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4603
J9 ADDICT BEHAV
JI Addict. Behav.
PD SEP
PY 2012
VL 37
IS 9
BP 1046
EP 1053
DI 10.1016/j.addbeh.2012.04.011
PG 8
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA 983TJ
UT WOS:000307141300007
PM 22626890
ER
PT J
AU Khoury, P
Zagallo, P
Talar-Williams, C
Santos, CS
Dinerman, E
Holland, NC
Klion, AD
AF Khoury, P.
Zagallo, P.
Talar-Williams, C.
Santos, C. S.
Dinerman, E.
Holland, N. C.
Klion, A. D.
TI Serum biomarkers are similar in Churg-Strauss syndrome and
hypereosinophilic syndrome
SO ALLERGY
LA English
DT Article
DE Churg-Strauss syndrome; eosinophilia; hypereosinophilic syndrome
ID EOSINOPHIL CATIONIC PROTEIN; DISEASE-ACTIVITY; MARKER; ASTHMA; CELLS;
ACTIVATION; ANTIBODIES; EOTAXIN-3; CHEMOKINE; LEVEL
AB Rationale ChurgStrauss syndrome (CSS) and hypereosinophilic syndrome (HES) overlap considerably in clinical presentation. A reliable means of distinguishing between these groups of patients is needed, especially in the setting of glucocorticoid therapy. Methods A retrospective chart review of 276 adult subjects referred for evaluation of eosinophilia > 1500/mu l was performed, and subjects with a documented secondary cause of eosinophilia or a PDGFR -positive myeloproliferative neoplasm were excluded. The remaining subjects were assessed for the presence of American College of Rheumatology (ACR) criteria. Laboratory and clinical parameters were compared between subjects with biopsy-proven vasculitis (CSS; n = 8), =4 ACR criteria (probable CSS; n = 21), HES with asthma and/or sinusitis without other CSS-defining criteria (HESwAS; n = 20), HES without asthma or sinusitis (HES; n = 18), and normal controls (n = 8). Serum biomarkers reported to be associated with CSS were measured using standard techniques. Results There were no differences between the subjects with definite or probable CSS or HES with respect to age, gender, or maintenance steroid dose. Serum CCL17, IL-8, and eotaxin levels were significantly increased in eosinophilic subjects as compared to normal controls, but were similar between the eosinophilic groups. Serum CCL17 correlated with eosinophil count (P < 0.0001, r = 0.73), but not with prednisone dose. Conclusions In patients with a history of asthma and sinusitis, distinguishing between ANCA-negative CSS and PDGFR -ne-gative HES is difficult because of significant overlap in clinical presentation and biomarker profiles.
C1 [Khoury, P.; Santos, C. S.; Dinerman, E.; Klion, A. D.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Zagallo, P.] Univ Arizona, Dept Immunobiol, Tucson, AZ USA.
[Talar-Williams, C.] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Holland, N. C.] NCI, Parasit Dis Lab, Clin Res Directorate CMRP, SAIC Frederick Inc, Frederick, MD 21701 USA.
RP Khoury, P (reprint author), NIAID, Parasit Dis Lab, NIH, 4 Mem Dr,Bldg 4,Room B1-28, Bethesda, MD 20892 USA.
EM khouryp@niaid.nih.gov
OI Klion, Amy/0000-0002-4986-5326
FU Division of Intramural Research, NIAID, National Institutes of Health;
National Cancer Institute, National Institutes of Health
[HHSN2610080001E]; National Institute of Allergy and Infectious Diseases
FX Division of Intramural Research, NIAID, National Institutes of Health;
Clinical Trials: NCT00001406. 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. HHSN2610080001E. 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. This research was supported [in part] by the National
Institute of Allergy and Infectious Diseases.
NR 24
TC 17
Z9 20
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0105-4538
J9 ALLERGY
JI Allergy
PD SEP
PY 2012
VL 67
IS 9
BP 1149
EP 1156
DI 10.1111/j.1398-9995.2012.02873.x
PG 8
WC Allergy; Immunology
SC Allergy; Immunology
GA 986XJ
UT WOS:000307380000008
PM 22775568
ER
PT J
AU Bornstein, MH
Putnick, DL
Suwalsky, JTD
AF Bornstein, Marc H.
Putnick, Diane L.
Suwalsky, Joan T. D.
TI A Longitudinal Process Analysis of Mother-Child Emotional Relationships
in a Rural Appalachian European American Community
SO AMERICAN JOURNAL OF COMMUNITY PSYCHOLOGY
LA English
DT Article
DE Emotional availability; Maternal age; Appalachia
ID ADOLESCENT MOTHERS; SOCIAL SUPPORT; CHRONOLOGICAL AGE; INFANT;
PARENTHOOD; QUALITY; AVAILABILITY; DETERMINANTS; TRANSITION; BEHAVIORS
AB This prospective longitudinal study examines emotional relationships in 58 Appalachian mother-child dyads observed at home at 5 and 20 months. Between infancy and toddlerhood, 3 of 4 dimensions of dyadic emotional relationships were stable, and three remained continuous in their mean level. Increasing maternal age was associated with greater maternal sensitivity and structuring and with more responsive and involving children. Marital status and father presence in the home as well as maternal openness, parenting knowledge, investment, and satisfaction accounted for effects of maternal age on dyadic emotional relationships. This longitudinal process analysis provides unique insights into temporal dynamics of mother-child emotional relationships and their determinants in an underserved and underresearched US community. Implications for community-specific interventions are discussed.
C1 [Bornstein, Marc H.; Putnick, Diane L.; Suwalsky, Joan T. D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Publ Hlth Serv, Bethesda, MD 20892 USA.
RP Bornstein, MH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Publ Hlth Serv, Rockledge 1,Suite 8030,6705 Rockledge Dr,MSC 7971, Bethesda, MD 20892 USA.
EM Marc_H_Bornstein@nih.gov; putnickd@mail.nih.gov
OI Putnick, Diane/0000-0002-6323-749X
FU Intramural NIH HHS [Z01 HD001119-20]
NR 77
TC 0
Z9 0
U1 6
U2 10
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0091-0562
EI 1573-2770
J9 AM J COMMUN PSYCHOL
JI Am. J. Community Psychol.
PD SEP
PY 2012
VL 50
IS 1-2
BP 89
EP 100
DI 10.1007/s10464-011-9479-1
PG 12
WC Public, Environmental & Occupational Health; Psychology,
Multidisciplinary; Social Work
SC Public, Environmental & Occupational Health; Psychology; Social Work
GA 985MX
UT WOS:000307271900008
PM 22080397
ER
PT J
AU Vlaanderen, J
Lan, Q
Kromhout, H
Rothman, N
Vermeulen, R
AF Vlaanderen, Jelle
Lan, Qing
Kromhout, Hans
Rothman, Nathaniel
Vermeulen, Roel
TI Occupational benzene exposure and the risk of chronic myeloid leukemia:
A meta-analysis of cohort studies incorporating study quality dimensions
SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE
LA English
DT Article
DE benzene; chronic myeloid leukemia; occupational exposure; meta-analysis
ID CHRONIC MYELOGENOUS LEUKEMIA; DISTRIBUTION WORKERS; PETROLEUM WORKERS;
UPDATED MORTALITY; OIL REFINERY; CRUDE-OIL; CANCER; POPULATION; TEXAS;
SHANGHAI
AB Objective We documented previously that if study quality is accounted for, evidence from occupational cohort studies on benzene supports a possible association with some lymphoma subtypes, in particular multiple myeloma, and acute and chronic lymphocytic leukemia. Here, we extend these analyses to chronic myeloid leukemia (CML). Methods Three strategies to assess study quality (stratification by the year-of-start of follow-up, stratification by the strength of the reported acute myeloid leukemia (AML) association, and stratification by the quality of benzene exposure assessment) were employed in a meta-analysis of occupational benzene exposure and CML. We hypothesized that stratification by these study quality dimensions would identify a subgroup of occupational cohort studies that is most informative for the evaluation of the possible association between benzene and CML. Results The overall meta-relative risk (mRR) was non-significantly elevated (1.23; 95% confidence interval (CI): 0.931.63). The mRRs increased with increasing study quality for all dimensions with a significant elevation for studies with start of follow-up after 1970 (1.67; 95% CI: 1.022.74). The highest study quality stratum for AML significance and exposure quality showed an elevated but non-significant increased mRR (1.40; 95% CI: 0.862.27, and 1.68; 95% CI: 0.743.84, respectively). Conclusions Although limited by low statistical power, the current meta-analysis provides support for a possible association of occupational exposure to benzene and the risk of CML. Am. J. Ind. Med. 55:779785, 2012. (c) 2012 Wiley Periodicals, Inc.
C1 [Vlaanderen, Jelle; Kromhout, Hans; Vermeulen, Roel] Univ Utrecht, IRAS, Div Environm Epidemiol, NL-3584 CK Utrecht, Netherlands.
[Lan, Qing; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, US Dept HHS, NIH, Bethesda, MD 20892 USA.
RP Vermeulen, R (reprint author), Univ Utrecht, IRAS, Div Environm Epidemiol, Jenalaan 18D, NL-3584 CK Utrecht, Netherlands.
EM r.c.h.vermeulen@uu.nl
RI Vermeulen, Roel/F-8037-2011
OI Vermeulen, Roel/0000-0003-4082-8163
FU International Agency for Research on Cancer; European commission
FX Part of the work reported in this article was undertaken during the
tenure of a Postdoctoral Fellowship from the International Agency for
Research on Cancer, partially supported by the European commission FP7
Marie Curie Actions-People-Cofunding of regional, national, and
international programmes (COFUND).
NR 34
TC 16
Z9 16
U1 0
U2 17
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0271-3586
J9 AM J IND MED
JI Am. J. Ind. Med.
PD SEP
PY 2012
VL 55
IS 9
BP 779
EP 785
DI 10.1002/ajim.22087
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 986YX
UT WOS:000307384700004
PM 22729623
ER
PT J
AU Belizan, JM
McClure, EM
Goudar, SS
Pasha, O
Esamai, F
Patel, A
Chomba, E
Garces, A
Wright, LL
Koso-Thomas, M
Moore, J
Althabe, F
Kodkany, BS
Sami, N
Manasyan, A
Derman, RJ
Liechty, EA
Hibberd, P
Carlo, WA
Hambidge, KM
Buekens, P
Jobe, AH
Goldenberg, RL
AF Belizan, Jose M.
McClure, Elizabeth M.
Goudar, Shivaprasad S.
Pasha, Omrana
Esamai, Fabian
Patel, Archana
Chomba, Elwyn
Garces, Ana
Wright, Linda L.
Koso-Thomas, Marion
Moore, Janet
Althabe, Fernando
Kodkany, Bhala S.
Sami, Neelofar
Manasyan, Albert
Derman, Richard J.
Liechty, Edward A.
Hibberd, Patricia
Carlo, Waldemar A.
Hambidge, K. Michael
Buekens, Pierre
Jobe, Alan H.
Goldenberg, Robert L.
TI Neonatal Death in Low- to Middle-Income Countries: A Global Network
Study
SO AMERICAN JOURNAL OF PERINATOLOGY
LA English
DT Article
DE neonatal mortality; low-income countries; preterm birth
ID MORTALITY; RATES; CARE
AB Objective To determine population-based neonatal mortality rates in low- and middle-income countries and to examine gestational age, birth weight, and timing of death to assess the potentially preventable neonatal deaths.
Methods A prospective observational study was conducted in communities in five low-income countries (Kenya, Zambia, Guatemala, India, and Pakistan) and one middle-income country (Argentina). Over a 2-year period, all pregnant women in the study communities were enrolled by trained study staff and their infants followed to 28 days of age.
Results Between October 2009 and March 2011, 153,728 babies were delivered and followed through day 28. Neonatal death rates ranged from 41 per 1000 births in Pakistan to 8 per 1000 in Argentina; 54% of the neonatal deaths were >37 weeks and 46% weighed 2500 g or more. Half the deaths occurred within 24 hours of delivery.
Conclusion In our population-based low- and middle-income country registries, the majority of neonatal deaths occurred in babies >37 weeks' gestation and almost half weighed at least 2500 g. Most deaths occurred shortly after birth. With access to better medical care and hospitalization, especially in the intrapartum and early neonatal period, many of these neonatal deaths might be prevented.
C1 [McClure, Elizabeth M.] Res Triangle Inst, Dept Stat & Epidemiol, Durham, NC 27709 USA.
[Belizan, Jose M.; Althabe, Fernando] Inst Clin Effectiveness, Buenos Aires, DF, Argentina.
[McClure, Elizabeth M.; Moore, Janet] Jawaharlal Nehru Med Coll, Belgaum, India.
[Pasha, Omrana; Sami, Neelofar] Aga Khan Univ, Karachi, Pakistan.
[Esamai, Fabian] Moi Univ, Eldoret, Kenya.
[Patel, Archana] Lata Med Res Fdn, Nagpur, Maharashtra, India.
[Patel, Archana] Indira Med Coll, Nagpur, Maharashtra, India.
[Chomba, Elwyn; Manasyan, Albert] Univ Zambia, Lusaka, Zambia.
[Garces, Ana] San Carlos Univ, Guatemala City, Guatemala.
[Wright, Linda L.; Koso-Thomas, Marion] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Derman, Richard J.] Christiana Hlth Care, Newark, DE USA.
[Liechty, Edward A.] Indiana Univ, Indianapolis, IN 46204 USA.
[Hibberd, Patricia] Massachusetts Gen Hosp Children, Boston, MA USA.
[Carlo, Waldemar A.] Univ Alabama Birmingham, Birmingham, AL USA.
[Hambidge, K. Michael] Univ Colorado, Hlth Sci Ctr, Denver, CO USA.
[Buekens, Pierre] Tulane Sch Publ Hlth & Trop Med, New Orleans, LA USA.
[Jobe, Alan H.] Univ Cincinnati, Cincinnati, OH USA.
[Goldenberg, Robert L.] Columbia Univ, New York, NY USA.
RP McClure, EM (reprint author), Res Triangle Inst, Dept Stat & Epidemiol, Durham, NC 27709 USA.
EM mcclure@rti.org
OI GOUDAR, SHIVAPRASAD/0000-0002-8680-7053; Belizan,
Jose/0000-0002-8412-3010
FU National Institutes of Health from Global Network for Women's and
Children's Health Research [U01 HD040477, U01 HD0434475, U01 HD043464,
U01 HD040657, U01 HD042372, U01 HD040607, U01 HD040636, U01 HD058322]
FX Supported by National Institutes of Health grants from the Global
Network for Women's and Children's Health Research (U01 HD040477, U01
HD0434475, U01 HD043464, U01 HD040657, U01 HD042372, U01 HD040607, U01
HD040636, U01 HD058322).
NR 16
TC 18
Z9 18
U1 0
U2 7
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0735-1631
J9 AM J PERINAT
JI Am. J. Perinatol.
PD SEP
PY 2012
VL 29
IS 8
BP 649
EP 655
DI 10.1055/s-0032-1314885
PG 7
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 991CU
UT WOS:000307679900012
PM 22644832
ER
PT J
AU Li, WH
Lang, LX
Niu, G
Guo, N
Ma, Y
Kiesewetter, DO
Shen, BZ
Chen, XY
AF Li, Weihua
Lang, Lixin
Niu, Gang
Guo, Ning
Ma, Ying
Kiesewetter, Dale O.
Shen, Baozhong
Chen, Xiaoyuan
TI N-Succinimidyl 4-[F-18]-fluoromethylbenzoate-labeled dimeric RGD peptide
for imaging tumor integrin expression
SO AMINO ACIDS
LA English
DT Article
DE Integrin alpha v beta 3; RGD peptide dimer; Positron emission
tomography; N-Succinimidyl 4-[F-18]-fluoromethylbenzoate ([F-18]SFMB)
ID PET; PROTEINS; AGENT
AB RGD peptides, radiolabeled with F-18, have been used in the clinic for PET imaging of tumor angiogenesis in cancer patients. RGD peptides are typically labeled using a prosthetic group such as N-succinimidyl 4-[F-18]-fluorobenzoate ([F-18]SFB) or 4-nitrophenyl 2-[F-18]-fluoropropionate ([F-18]NPFP). However, the complex radiosynthetic procedures have impeded their broad application in clinical studies. We previously radiolabeled proteins and peptides with the prosthetic group, N-succinimidyl 4-[F-18]-fluoromethylbenzoate ([F-18]SFMB), which was prepared in a simple one-step procedure. In this study, we labeled a PEGylated cyclic RGD peptide dimer, PEG(3)-E[c(RGDyK)](2) (PRGD2), using [F-18]SFMB and evaluated for imaging tumor alpha v beta 3 integrin expression with positron emission tomography (PET). [F-18]SFMB was prepared in one step using [F-18]fluoride displacement of a nitrobenzenesulfonate leaving group under mild reaction conditions followed by HPLC purification. The F-18-labeled peptide, [F-18]FMBPRGD2 was prepared by coupling PRGD2 with [F-18]SFMB in pH 8.6 borate buffer and purified with HPLC. The direct labeling on BMBPRGD2 was also attempted. A Siemens Inveon PET was used to image the uptake of the [F-18]FMBPRGD2 into a U87MG xenograft mouse model. [F-18]FMBPRGD2, was prepared with a 15% overall radiochemical yield (uncorrected) in a total synthesis time of 90 min, which was considerably shorter than the preparation of [F-18]SFB- and [F-18]NPFP-labeled RGD peptides. The direct labeling, however, was not successful. High quality microPET images using [F-18]FMBPRGD2 clearly visualized tumors by 15 min with good target to background ratio. Early tracer accumulation in the bladder suggests fast renal clearance. No obvious bone uptake can be detected even at 4-h time point indicating that fluorine attachment is stable in mice. In conclusion, N-succinimidyl 4-[F-18]-fluoromethylbenzoate ([F-18]SFMB) prosthetic group can be a good alternative for labeling RGD peptides to image alpha v beta 3 integrin expression and for labeling other peptides.
C1 [Li, Weihua; Lang, Lixin; Niu, Gang; Guo, Ning; Ma, Ying; Kiesewetter, Dale O.; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
[Li, Weihua; Shen, Baozhong] Harbin Med Univ, Affiliated Hosp 4, Dept Med Imaging & Nucl Med, Harbin 150001, Peoples R China.
RP Chen, XY (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, 31 Ctr Dr,Suite 1C14, Bethesda, MD 20892 USA.
EM shawn.chen@nih.gov
FU intramural programs of the National Institute of Biomedical Imaging and
Bioengineering, National Institutes of Health; International Cooperative
Program of the National Science Foundation of China (NSFC) [81028009];
International Cooperation Project of the Chinese Ministry of Science and
Technology [2009DFB30040]
FX This work was supported by the intramural programs of the National
Institute of Biomedical Imaging and Bioengineering, National Institutes
of Health, the International Cooperative Program of the National Science
Foundation of China (NSFC) (81028009), and the International Cooperation
Project of the Chinese Ministry of Science and Technology
(2009DFB30040).
NR 18
TC 6
Z9 6
U1 2
U2 17
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 2012
VL 43
IS 3
BP 1349
EP 1357
DI 10.1007/s00726-011-1208-4
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 989BV
UT WOS:000307536100031
PM 22209865
ER
PT J
AU Gao, XH
Wang, Q
Wang, J
Wang, CS
Lu, L
Gao, R
Huan, F
Dixon, D
Xiao, H
AF Gao, Xiaohua
Wang, Qiang
Wang, Jun
Wang, Changsong
Lu, Liang
Gao, Rong
Huan, Fei
Dixon, Darlene
Xiao, Hang
TI Expression of calmodulin in germ cells is associated with
fenvalerate-induced male reproductive toxicity
SO ARCHIVES OF TOXICOLOGY
LA English
DT Article
DE Calmodulin; Fenvalerate; Testis; Germ cells; Male reproductive system
ID IN-VITRO; CAMKII; SPERM; OSTEOCLASTS; MOTILITY; BINDING; ASSAYS; MICE
AB Exposure to fenvalerate was demonstrated to be toxic to the male reproductive system. Our previous data revealed that intracellular calcium plays an important role in regulating the above toxicity, through actions on both T-type calcium channels and endoplasmic reticulum calcium signals. The present study explored the effects of fenvalerate on the expression of calmodulin in mouse testis and GC-2spd(ts) cells, and its association with fenvalerate-induced male reproductive toxicity. Male mice were subjected to different doses (3.71, 18.56, 37.12, 92.81 mg/kg bw) of fenvalerate or vehicle control for 4 weeks. Expression of calmodulin was determined by real-time polymerase chain reaction (PCR) and Western blot analysis in mouse testis. Similar approaches were utilized in GC-2spd(ts) cells cultured with 5 mu M fenvalerate at different time points. In the in vivo study, all mice survived through the entire 4 weeks. Administration of fenvalerate resulted in a dose-dependent reduction in testis weight/body weight, sperm motility, and increased head abnormality rate. By histological staining, mice treated with fenvalerate at higher doses showed dilated seminiferous tubules and disturbed arrangement of spermatogenic cells. Meanwhile, both mRNA and protein expression of calmodulin were significantly increased in the testes of mice exposed to fenvalerate compared to control mice. Moreover, in the in vitro study, 5 mu M fenvalerate significantly increased the expression of calmodulin at the mRNA and protein levels in GC-2spd(ts) cells after 8 h of incubation and sustained these levels for at least 24 h. Collectively, these data suggested that enhanced expression of calmodulin correlates with male reproductive damage induced by fenvalerate.
C1 [Gao, Xiaohua; Wang, Qiang; Wang, Jun; Wang, Changsong; Lu, Liang; Gao, Rong; Huan, Fei; Xiao, Hang] Nanjing Med Univ, Dept Toxicol, Nanjing 210029, Jiangsu, Peoples R China.
[Gao, Xiaohua; Wang, Qiang; Wang, Jun; Wang, Changsong; Lu, Liang; Gao, Rong; Huan, Fei; Xiao, Hang] Nanjing Med Univ, Sch Publ Hlth, Key Lab Modern Toxicol, Minist Educ, Nanjing 210029, Jiangsu, Peoples R China.
[Gao, Xiaohua; Dixon, Darlene] NIEHS, Mol Pathogenesis Grp, Natl Toxicol Program NTP, Lab Branch,Div NTP,NIH,DHHS, Res Triangle Pk, NC 27709 USA.
RP Xiao, H (reprint author), Nanjing Med Univ, Dept Toxicol, 140 Hanzhong Rd, Nanjing 210029, Jiangsu, Peoples R China.
EM dixon@niehs.nih.gov; hxiao@njmu.edu.cn
FU National Natural Science Foundation of China [30571555, 30771831];
Priority Academic Program Development (PAPD) of Jiangsu Higher Education
Institutions; Intramural Research Program of the NIH; NIEHS; NTP
FX The authors would like to thank Drs. Gordon Flake and Ronald Herbert for
their critical review of this manuscript. This work was supported by the
National Natural Science Foundation of China (30571555 and 30771831) and
the Priority Academic Program Development (PAPD) of Jiangsu Higher
Education Institutions. This research was also supported, in part, by
the Intramural Research Program of the NIH, NIEHS and NTP.
NR 28
TC 8
Z9 10
U1 1
U2 5
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0340-5761
J9 ARCH TOXICOL
JI Arch. Toxicol.
PD SEP
PY 2012
VL 86
IS 9
BP 1443
EP 1451
DI 10.1007/s00204-012-0825-3
PG 9
WC Toxicology
SC Toxicology
GA 992HP
UT WOS:000307766500013
PM 22437841
ER
PT J
AU Shimada, H
Hashiguchi, T
Yasutake, A
Waalkes, MP
Imamura, Y
AF Shimada, Hideaki
Hashiguchi, Takashi
Yasutake, Akira
Waalkes, Michael P.
Imamura, Yorishige
TI Sexual dimorphism of cadmium-induced toxicity in rats: involvement of
sex hormones
SO ARCHIVES OF TOXICOLOGY
LA English
DT Article
DE Cadmium toxicity; Sex difference; Progesterone; beta-Estradiol; Rat
ID METALLOTHIONEIN INDUCTION; PROGESTERONE PRETREATMENT; ESTROGEN;
EXPOSURE; MICE; HEPATOTOXICITY; ACTIVATION; PREGNANCY; SALTS
AB The toxic effect of cadmium varies with sex in experimental animals. Previous studies have demonstrated that pretreatment of male Fischer 344 (F344) rats with the female sex hormone progesterone markedly enhances the susceptibility to cadmium, suggesting a role for progesterone in the sexual dimorphism of cadmium toxicity. In the present study, we attempted to further elucidate the mechanism for sex differences in cadmium-induced toxicity in F344 rats. A single exposure to cadmium (5.0 mg Cd/kg, sc) was lethal in 10/10 (100 %) female compared with 6/10 (60 %) male rats. Using a lower dose of cadmium (3.0 mg Cd/kg), circulating alanine aminotransferase activity, indicative of hepatotoxicity, was highly elevated in the cadmium treated females but not in males. However, no gender-based differences occurred in the hepatic cadmium accumulation, metallothionein or glutathione levels. When cadmium (5.0 mg Cd/kg) was administered to young rats at 5 weeks of age, the sex-related difference in lethality was minimal. Furthermore, although ovariectomy blocked cadmium-induced lethality, the lethal effects of the metal were restored by pretreatment with progesterone (40 mg/kg, sc, 7 consecutive days) or beta-estradiol (200 mu g/kg, sc, 7 consecutive days) to ovariectomized rats. These results provide further evidence that female sex hormones such as progesterone and beta-estradiol are involved in the sexual dimorphism of cadmium toxicity in rats.
C1 [Shimada, Hideaki; Hashiguchi, Takashi] Kumamoto Univ, Fac Educ, Kumamoto 8608555, Japan.
[Yasutake, Akira] Natl Inst Minamata Dis, Biochem Sect, Minamata, Kumamoto 8670008, Japan.
[Waalkes, Michael P.] NIEHS, Inorgan Toxicol Grp, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Imamura, Yorishige] Nihon Pharmaceut Univ, Ina, Saitama 3620806, Japan.
RP Shimada, H (reprint author), Kumamoto Univ, Fac Educ, 2-40-1 Kurokami, Kumamoto 8608555, Japan.
EM hshimada@gpo.kumamoto-u.ac.jp
FU National Toxicology Program, National Institute of Environmental Health
Sciences (NIEHS)
FX This research was supported in part by the National Toxicology Program,
National Institute of Environmental Health Sciences (NIEHS). This
article may be the work product of an employee or group of employees of
the NIEHS, National Institutes of Health (NIH), however, the statements
contained herein do not necessarily represent the statements, opinions
or conclusions of the NIEHS, NIH or the United States Government.
NR 29
TC 6
Z9 6
U1 2
U2 10
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0340-5761
J9 ARCH TOXICOL
JI Arch. Toxicol.
PD SEP
PY 2012
VL 86
IS 9
BP 1475
EP 1480
DI 10.1007/s00204-012-0844-0
PG 6
WC Toxicology
SC Toxicology
GA 992HP
UT WOS:000307766500016
PM 22466070
ER
PT J
AU Kasiviswanathan, R
Collins, TRL
Copeland, WC
AF Kasiviswanathan, Rajesh
Collins, Tammy R. L.
Copeland, William C.
TI The interface of transcription and DNA replication in the mitochondria
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
LA English
DT Review
DE Mitochondrial DNA replication; DNA polymerase gamma; Twinkle helicase;
Mitochondrial topoisomerase; Single-stranded DNA binding protein
ID SINGLE-STRANDED-DNA; PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; BASE
EXCISION-REPAIR; STRUCTURE-FUNCTION DEFECTS; CLOSED CIRCULAR TEMPLATE;
P55 ACCESSORY SUBUNIT; POLYMERASE-GAMMA; BINDING-PROTEIN; RIBONUCLEOTIDE
INCORPORATION; MAMMALIAN MITOCHONDRIA
AB DNA replication of the mitochondrial genome is unique in that replication is not primed by RNA derived from dedicated primases, but instead by extension of processed RNA transcripts laid down by the mitochondria! RNA polymerase. Thus, the RNA polymerase serves not only to generate the transcripts but also the primers needed for mitochondrial DNA replication. The interface between this transcription and DNA replication is not well understood but must be highly regulated and coordinated to carry out both mitochondrial DNA replication and transcription. This review focuses on the extension of RNA primers for DNA replication by the replication machinery and summarizes the current models of DNA replication in mitochondria as well as the proteins involved in mitochondrial DNA replication, namely, the DNA polymerase gamma and its accessory subunit, the mitochondrial DNA helicase, the single-stranded DNA binding protein, topoisomerase I and III alpha and RNaseH1. This article is part of a Special Issue entitled: Mitochondrial Gene Expression. Published by Elsevier B.V.
C1 [Kasiviswanathan, Rajesh; Collins, Tammy R. L.; Copeland, William C.] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Copeland, WC (reprint author), NIEHS, Mol Genet Lab, NIH, 111 TW Alexander Dr,Bldg 101,Rm E316, Res Triangle Pk, NC 27709 USA.
EM copelan1@niehs.nih.gov
FU NIH, National Institute of Environmental Health Sciences [ES 065078, ES
065080]
FX We thank Drs. Matthew Longley and Matthew Young for critically reading
this manuscript. This research was supported by the Intramural Research
Program of the NIH, National Institute of Environmental Health Sciences
(ES 065078 and ES 065080).
NR 111
TC 23
Z9 23
U1 1
U2 21
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1874-9399
J9 BBA-GENE REGUL MECH
JI Biochim. Biophys. Acta-Gene Regul. Mech.
PD SEP-OCT
PY 2012
VL 1819
IS 9-10
SI SI
BP 970
EP 978
DI 10.1016/j.bbagrm.2011.12.005
PG 9
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 987QJ
UT WOS:000307431900008
PM 22207204
ER
PT J
AU Costanzi, S
Kumar, TS
Balasubramanian, R
Harden, TK
Jacobson, KA
AF Costanzi, Stefano
Kumar, T. Santhosh
Balasubramanian, Ramachandran
Harden, T. Kendall
Jacobson, Kenneth A.
TI Virtual screening leads to the discovery of novel non-nucleotide P2Y(1)
receptor antagonists
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE P2Y(1) receptor; G protein-coupled receptor; Antagonist; Virtual
screening; Molecular modeling
ID PHOSPHOLIPASE-C; ANALOGS; ACTIVATION
AB The P2Y(1) receptor (P2Y(1)R) is a G protein-coupled receptor naturally activated by extracellular ADP. Its stimulation is an essential requirement of ADP-induced platelet aggregation, thus making antagonists highly sought compounds for the development of antithrombotic agents. Here, through a virtual screening campaign based on a pharmacophoric representation of the common characteristics of known P2Y(1)R ligands and the putative shape and size of the receptor binding pocket, we have identified novel antagonist hits of mu M affinity derived from a N,N'-bis-arylurea chemotype. Unlike the vast majority of known P2Y(1)R antagonists, these drug-like compounds do not have a nucleotidic scaffold or highly negatively charged phosphate groups. Hence, our compounds may provide a direction for the development of receptor probes with altered physicochemical properties. Published by Elsevier Ltd.
C1 [Costanzi, Stefano] NIH, Lab Biol Modeling, Bethesda, MD 20892 USA.
[Kumar, T. Santhosh; Balasubramanian, Ramachandran; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Lab Biooorgan Chem, NIH, Bethesda, MD 20892 USA.
[Harden, T. Kendall] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA.
RP Costanzi, S (reprint author), American Univ, Dept Chem, Washington, DC 20016 USA.
EM costanzi@american.edu; kajacobs@helix.nih.gov
RI Jacobson, Kenneth/A-1530-2009; Costanzi, Stefano/G-8990-2013;
OI Jacobson, Kenneth/0000-0001-8104-1493; Costanzi,
Stefano/0000-0003-3183-7332
FU NIDDK; National Institutes of General Medical Sciences [GM38213]
FX This research was supported in part by the Intramural Research Program
of NIDDK and by the National Institutes of General Medical Sciences
(GM38213).
NR 20
TC 7
Z9 7
U1 0
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD SEP 1
PY 2012
VL 20
IS 17
BP 5254
EP 5261
DI 10.1016/j.bmc.2012.06.044
PG 8
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 993BI
UT WOS:000307828600021
PM 22831801
ER
PT J
AU Simonyan, K
Horwitz, B
Jarvis, ED
AF Simonyan, Kristina
Horwitz, Barry
Jarvis, Erich D.
TI Dopamine regulation of human speech and bird song: A critical review
SO BRAIN AND LANGUAGE
LA English
DT Review
DE Speech and song control; Basal ganglia; Brain networks;
Neurotransmission
ID CORTICAL LARYNX AREA; AVIAN BASAL GANGLIA; SUBTHALAMIC NUCLEUS;
PARKINSONS-DISEASE; RHESUS-MONKEY; SOCIAL-CONTEXT; INDIRECT PATHWAYS;
SQUIRREL-MONKEY; SPINY NEURONS; MOTOR CORTEX
AB To understand the neural basis of human speech control, extensive research has been done using a variety of methodologies in a range of experimental models. Nevertheless, several critical questions about learned vocal motor control still remain open. One of them is the mechanism(s) by which neurotransmitters, such as dopamine, modulate speech and song production. In this review, we bring together the two fields of investigations of dopamine action on voice control in humans and songbirds, who share similar behavioral and neural mechanisms for speech and song production. While human studies investigating the role of dopamine in speech control are limited to reports in neurological patients, research on dopaminergic modulation of bird song control has recently expanded our views on how this system might be organized. We discuss the parallels between bird song and human speech from the perspective of dopaminergic control as well as outline important differences between these species. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Simonyan, Kristina] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA.
[Simonyan, Kristina] Mt Sinai Sch Med, Dept Otolaryngol, New York, NY USA.
[Horwitz, Barry] Natl Inst Deafness & Other Commun Disorders, Brain Imaging & Modeling Sect, NIH, Bethesda, MD USA.
[Jarvis, Erich D.] Duke Univ, Dept Neurobiol, Howard Hughes Med Inst, Durham, NC USA.
RP Simonyan, K (reprint author), Mt Sinai Sch Med, Dept Neurol, Box 1137, New York, NY 10029 USA.
EM kristina.simonyan@mssm.edu
RI Jarvis, Erich/A-2319-2008;
OI Jarvis, Erich/0000-0001-8931-5049; Simonyan,
Kristina/0000-0001-7444-0437
FU National Institute on Deafness and Other Communication Disorders;
National Institutes of Health [DC009620]; Howard Hughes Medical
Institute; National Institute of Mental Health [MH62083]
FX This work was supported by the National Institute on Deafness and Other
Communication Disorders, National Institutes of Health (DC009620 to
K.S., Intramural Program to B.H.), the Howard Hughes Medical Institute
and the National Institute of Mental Health (MH62083 to E.D.J.).
NR 129
TC 24
Z9 24
U1 0
U2 38
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0093-934X
J9 BRAIN LANG
JI Brain Lang.
PD SEP
PY 2012
VL 122
IS 3
BP 142
EP 150
DI 10.1016/j.bandl.2011.12.009
PG 9
WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences;
Psychology, Experimental
SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences &
Neurology; Psychology
GA 992SC
UT WOS:000307799000003
PM 22284300
ER
PT J
AU Joy, MS
La, M
Wang, JZ
Bridges, AS
Hu, YC
Hogan, SL
Frye, RF
Blaisdell, J
Goldstein, JA
Dooley, MA
Brouwer, KLR
Falk, RJ
AF Joy, Melanie S.
La, Mary
Wang, Jinzhao
Bridges, Arlene S.
Hu, Yichun
Hogan, Susan L.
Frye, Reginald F.
Blaisdell, Joyce
Goldstein, Joyce A.
Dooley, Mary Anne
Brouwer, Kim L. R.
Falk, Ronald J.
TI Cyclophosphamide and 4-hydroxycyclophosphamide pharmacokinetics in
patients with glomerulonephritis secondary to lupus and small vessel
vasculitis
SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
LA English
DT Article
DE 4-hydroxycylophosphamide; cyclophosphamide; glomerulonephritis; lupus
nephritis; pharmacogenomics; pharmacokinetics
ID CELL LUNG-CANCER; IFOSFAMIDE ACTIVATION; BREAST-CANCER; CLINICAL
PHARMACOKINETICS; SYSTEMIC VASCULITIS; MASS-SPECTROMETRY; NEPHRITIS;
METABOLISM; THERAPY; CYP2C9
AB WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT The pharmacokinetics of cyclophosphamide and 4-hydroxycyclophosphamide in cancer patients have been well described. The current study was conducted to document the pharmacokinetics of cyclophosphamide and 4-hydroxycyclophosphamide in patients with glomerulonephritis. The study was necessary due to the numerous clinical abnormalities that are present in glomerulonephritis (altered glomerular filtration rate, proteinuria, hypoalbuminaemia) which can alter the disposition of drugs. WHAT THIS STUDY ADDS This study documents the differences in pharmacokinetics of cyclophosphamide and 4-hydroxycyclophosphamide in glomerulonephritis vs. the cancer population. The current results demonstrate that clinical and pharmacogenetic covariates can both alter the disposition of cyclophosphamide and 4-hydroxycyclophosphamide in glomerulonephritis. AIMS Cyclophosphamide, the precursor to the active 4-hydroxycyclophosphamide, is used in active glomerulonephritis despite limited pharmacokinetics data. The pharmacokinetics of cyclophosphamide and 4-hydroxycyclophosphamide were evaluated. The influence of laboratory and pharmacogenomic covariates on pharmacokinetics was evaluated as a secondary aim. METHODS Glomerulonephritis patients (n = 23) participated in a pharmacokinetic evaluation. Blood was serially collected and assayed for cyclophosphamide and 4-hydroxycyclophosphamide by LC/MS methods. Kidney function, serum albumin and polymorphisms in drug metabolism or transport genes were evaluated. Analyses included non-compartmental pharmacokinetics and parametric and non-parametric statistics. RESULTS The mean area under the plasma concentrationtime curve (AUC(0,8)) data were 110 100 +/- 42 900 ng ml-1 h and 5388 +/- 2841 ng ml-1 h for cyclophosphamide and 4-hydroxycyclophosphamide, respectively. The mean metabolic ratio was 0.06 +/- 0.04. A statistically significant relationship was found between increased serum albumin and increased half-life (0.584, P = 0.007, 95% CI 0.176, 0.820) and a borderline relationship with AUC(0,8) (0.402, P = 0.079, 95% CI 0.064, 0.724) for 4-hydroxycyclophosphamide. Covariate relationships that trended toward significance for cyclophosphamide included decreased serum albumin and increased elimination rate constant (0.427, P = 0.061, 95% CI 0.738, 0.034), increased urinary protein excretion and increased AUC(0,8) (0.392, P = 0.064, 95% CI 0.699 to 0.037), decreased Cmax (0.367, P = 0.085, 95% CI 0.067, 0.684) and decreased plasma clearance (0.392, P = 0.064, 95% CI 0.699, 0.037). CYP2B6*9 variants vs. wildtype were found to have decreased elimination rate constant (P = 0.0005, 95% CI 0.033, 0.103), increased Vd (P = 0.0271, 95% CI -57.5, -4.2) and decreased Cmax (P = 0.0176, 95% CI 0.696, 6179) for cyclophosphamide. ABCB1 C3435T variants had a borderline decrease in cyclophosphamide elimination rate constant (P = 0.0858; 95% CI 0.005, 0.102). CONCLUSIONS Pharmacokinetics of cyclophosphamide and 4-hydroxycyclophosphamide in patients with lupus nephritis and small vessel vasculitis are similar. Clinical and pharmacogenetic covariates alter disposition of cyclophosphamide and 4-hydroxycyclophosphamide. Clinical findings of worsened glomerulonephritis lead to increased exposure to cyclophosphamide vs. the active 4-hydroxycyclophosphamide, which could have relevance in terms of clinical efficacy. The CYP2B6*9 and ABCB1 C3435T polymorphisms alter the pharmacokinetics of cyclophosphamide and 4-hydroxycyclophosphamide in glomerulonephritis.
C1 [Joy, Melanie S.; La, Mary; Wang, Jinzhao; Hu, Yichun; Hogan, Susan L.; Dooley, Mary Anne; Falk, Ronald J.] Univ N Carolina, Sch Med, UNC Kidney Ctr, Div Nephrol & Hypertens, Chapel Hill, NC 27599 USA.
[Joy, Melanie S.; Brouwer, Kim L. R.] Univ N Carolina, Dept Pharmacotherapy & Expt Therapeut, Carolina Eshelman Sch Pharm, Chapel Hill, NC 27599 USA.
[Bridges, Arlene S.] Univ N Carolina, Dept Pathol & Lab Med, Sch Med, Chapel Hill, NC 27599 USA.
[Frye, Reginald F.] Univ Florida, Coll Pharm, Dept Pharmacotherapy & Translat Res, Gainesville, FL USA.
[Blaisdell, Joyce; Goldstein, Joyce A.] NIEHS, Pharmacol Lab, Human Metab Grp, Res Triangle Pk, NC 27709 USA.
RP Joy, MS (reprint author), Univ N Carolina, Sch Med, UNC Kidney Ctr, Div Nephrol & Hypertens, CB 7155,7005 Burnett Womack Bldg, Chapel Hill, NC 27599 USA.
EM Melanie_Joy@med.unc.edu
RI BRIDGES, ARLENE/N-4534-2013;
OI Frye, Reginald/0000-0002-1841-1401
FU National Institutes of Health [K23DK64888]; General Clinical Research
Centers program of the Division of Research Resources, National
Institutes of Health [RR00046]; Clinical and Translational Science Award
[U54RR024383]; American College of Clinical Pharmacy Research
Institute's Frontier's Award; Intramural Research Program of NIH,
National Institute of Environmental Health Sciences under NIH intramural
project [Z01ES02124]
FX This research was funded, in part, by the National Institutes of Health
K23DK64888 (MSJ), General Clinical Research Centers program of the
Division of Research Resources, National Institutes of Health RR00046
(MSJ), Clinical and Translational Science Award U54RR024383 (MSJ), and
American College of Clinical Pharmacy Research Institute's Frontier's
Award (MSJ), and by the Intramural Research Program of NIH, National
Institute of Environmental Health Sciences under NIH intramural project
number Z01ES02124 (JB, JAG).
NR 39
TC 15
Z9 19
U1 1
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0306-5251
J9 BRIT J CLIN PHARMACO
JI Br. J. Clin. Pharmacol.
PD SEP
PY 2012
VL 74
IS 3
BP 445
EP 455
DI 10.1111/j.1365-2125.2012.04223.x
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 984UO
UT WOS:000307218100006
PM 22380717
ER
PT J
AU Steffens, S
Pacher, P
AF Steffens, Sabine
Pacher, Pal
TI Targeting cannabinoid receptor CB2 in cardiovascular disorders: promises
and controversies
SO BRITISH JOURNAL OF PHARMACOLOGY
LA English
DT Article
DE atherosclerosis; restenosis; neointima; myocardial infarction and
reperfusion injury; stroke; macrophages; smooth muscle cells;
endothelial cells
ID LOW-DENSITY-LIPOPROTEIN; RAT ISOLATED HEARTS; HEPATIC
ISCHEMIA/REPERFUSION INJURY; ACTIVATED ENDOCANNABINOID SYSTEM;
ISCHEMIA-REPERFUSION INJURY; ENDOTHELIAL-CELL ACTIVATION;
ARACHIDONOYL-L-SERINE; DRUG-ELUTING STENTS; INTERACTING PROTEINS;
OXIDATIVE STRESS
AB Cardiovascular disease is the leading cause of death and disability worldwide, which can be largely attributed to atherosclerosis, a chronic inflammation of the arteries characterized by lesions containing immune and smooth muscle cells, lipids and extracellular matrix. In recent years, the lipid endocannabinoid system has emerged as a new therapeutic target in variety of disorders associated with inflammation and tissue injury, including those of the cardiovascular system. The discovery that ?-9-tetrahydrocannabinol (?9-THC), the main active constituent of marijuana, inhibited atherosclerotic plaque progression via a cannabinoid 2 (CB2) receptor-dependent anti-inflammatory mechanism, and that certain natural and synthetic cannabinoid ligands could modulate the myocardial or cerebral ischaemiareperfusion-induced tissue damage, have stimulated impetus for a growing number of studies investigating the implication of CB2 receptors in atherosclerosis, restenosis, stroke, myocardial infarction and heart failure. The aim of this review is to update on recent findings and controversies on the role of CB2 receptors in cardiovascular disease. Particular emphasis will be placed on novel insights in the potential cellular targets of CB2 stimulation in cardiovascular system (e.g. endothelial and vascular smooth muscle cells, cardiomyocytes, infiltrating and/or resident monocytes/macrophages and leukocytes, etc.), their interplay and intracellular signalling mechanisms identified, as well as on experimental and clinical studies.
C1 [Steffens, Sabine] Univ Hosp, Div Cardiol, Fdn Med Res, Dept Internal Med, CH-1211 Geneva, Switzerland.
[Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD USA.
RP Steffens, S (reprint author), Univ Hosp, Div Cardiol, Fdn Med Res, Dept Internal Med, Ave Roseraie 64, CH-1211 Geneva, Switzerland.
EM sabine.steffens@unige.ch; pacher@mail.nih.gov
RI Pacher, Pal/B-6378-2008
OI Pacher, Pal/0000-0001-7036-8108
FU Swiss National Science Foundation [310030_130732_1]; Bangerter Rhyner;
OPO; Novartis; Swiss Life foundation; Intramural Research Program of
NIH/NIAAA
FX This publication was supported by grants from the Swiss National Science
Foundation (# 310030_130732_1), Bangerter Rhyner, OPO, Novartis and
Swiss Life foundation to Dr Steffens and the Intramural Research Program
of NIH/NIAAA to Dr Pacher. The authors are indebted to Dr George Kunos
for providing key resources and support.
NR 97
TC 32
Z9 32
U1 1
U2 19
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1188
J9 BRIT J PHARMACOL
JI Br. J. Pharmacol.
PD SEP
PY 2012
VL 167
IS 2
BP 313
EP 323
DI 10.1111/j.1476-5381.2012.02042.x
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 992NM
UT WOS:000307784100006
PM 22612332
ER
PT J
AU Olney, RC
Permuy, JW
Prickett, TCR
Han, JC
Espiner, EA
AF Olney, Robert C.
Permuy, Joseph W.
Prickett, Timothy C. R.
Han, Joan C.
Espiner, Eric A.
TI Amino-terminal propeptide of C-type natriuretic peptide (NTproCNP)
predicts height velocity in healthy children
SO CLINICAL ENDOCRINOLOGY
LA English
DT Article
ID CYCLASE-B SYSTEM; GROWTH-HORMONE; PREPUBERTAL CHILDREN; BONE-FORMATION;
LINEAR GROWTH; SERUM; OVEREXPRESSION; STANDARDS; MARKERS; PLASMA
AB Objective C-type natriuretic peptide (CNP) is a paracrine regulatory factor of the growth plate and plays a key role in endochondral growth. Its amino-terminal propeptide (NTproCNP) is an equimolar product of CNP biosynthesis and is easily measured in plasma. Preliminary studies suggest that NTproCNP levels correlate with height velocity in sheep and children. The objectives of the study were to correlate NTproCNP levels with height velocity and to define the reference range for plasma CNP and NTproCNP across childhood. Design This was a prospective, cross-sectional, observational study of healthy children. Patients Participants were 258 healthy children between 2months and 20years of age. Measurements Anthropometrics were obtained and CNP and NTproCNP levels were determined by radioimmunoassay. Results For both sexes, CNP and NTproCNP levels were high in infancy, lower in early childhood, rising during puberty, then falling to low adult levels. Levels of NTproCNP peaked at 14.1years in boys and 11.9years in girls, coincident with the age of peak height velocity. Levels of NTproCNP varied with pubertal status, peaking at genital Tanner stage IV in boys and III in girls. There was a highly significant correlation between NTproCNP and height velocity. Conclusions C-type natriuretic peptide plays an integral role in endochondral growth. We show here that CNP synthesis (as measured by NTproCNP levels in plasma) is closely related to linear growth in healthy children at all ages. We propose NTproCNP as a biomarker of linear growth.
C1 [Olney, Robert C.; Permuy, Joseph W.] Nemours Childrens Clin, Div Endocrinol, Jacksonville, FL 32207 USA.
[Prickett, Timothy C. R.; Espiner, Eric A.] Univ Otago, Dept Med, Christchurch, New Zealand.
[Han, Joan C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Metab & Neuroendocrinol, Bethesda, MD USA.
RP Olney, RC (reprint author), Nemours Childrens Clin, Div Endocrinol, Jacksonville, FL 32207 USA.
EM rolney@nemours.org
FU Quest Diagnostics, Inc.; The Nemours Research Programs
FX This project was supported by the grants from Quest Diagnostics, Inc.
and The Nemours Research Programs. The authors would like to thank Dr.
Nelly Mauras for providing data and samples on the previously reported
subjects, Tina Ewen for administrative assistance, and Shawn Sweeten and
Karl Mann for technical assistance with this study.
NR 36
TC 15
Z9 15
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0300-0664
J9 CLIN ENDOCRINOL
JI Clin. Endocrinol.
PD SEP
PY 2012
VL 77
IS 3
BP 416
EP 422
DI 10.1111/j.1365-2265.2012.04392.x
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 989TL
UT WOS:000307583300012
PM 22435455
ER
PT J
AU Kurtis, JD
Gwamaka, M
Fried, M
Duffy, PE
AF Kurtis, Jonathan D.
Gwamaka, Moses
Fried, Michal
Duffy, Patrick E.
TI A 29-Year-Old Immigrant With Chronic Diarrhea Reply
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Letter
C1 [Kurtis, Jonathan D.] Brown Univ, Sch Med, Ctr Int Hlth Res, Rhode Isl Hosp, Providence, RI 02912 USA.
[Kurtis, Jonathan D.] Brown Univ, Sch Med, Dept Pathol & Lab Med, Providence, RI 02912 USA.
[Gwamaka, Moses; Fried, Michal; Duffy, Patrick E.] Seattle Biomed Res Inst, Mother Offspring Malaria Studies Project, Washington, DC USA.
[Gwamaka, Moses] Muheza Designated Dist Hosp, Morogoro, Tanzania.
[Gwamaka, Moses] Sokoine Univ Agr, Morogoro, Tanzania.
[Fried, Michal; Duffy, Patrick E.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Bethesda, MD 20892 USA.
RP Duffy, PE (reprint author), NIAID, Lab Malaria Immunol & Vaccinol, NIH, 5640 Fishers Lane,Twinbrook 1 Bldg,Rm 1111, Rockville, MD 20852 USA.
EM patrick.duffy@nih.gov
NR 3
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 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD SEP 1
PY 2012
VL 55
IS 5
BP 748
EP 749
DI 10.1093/cid/cis525
PG 2
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 988NR
UT WOS:000307498300020
ER
PT J
AU Chipchase, L
Schabrun, S
Cohen, L
Hodges, P
Ridding, M
Rothwell, J
Taylor, J
Ziemann, U
AF Chipchase, Lucy
Schabrun, Siobhan
Cohen, Leonardo
Hodges, Paul
Ridding, Michael
Rothwell, John
Taylor, Janet
Ziemann, Ulf
TI A checklist for assessing the methodological quality of studies using
transcranial magnetic stimulation to study the motor system: An
international consensus study
SO CLINICAL NEUROPHYSIOLOGY
LA English
DT Article
DE Transcranial magnetic stimulation; Motor system; Consensus; Checklist;
Reporting; Expert
ID CORTICOMOTOR EXCITABILITY; CORTICAL PLASTICITY; IFCN COMMITTEE; DELPHI;
CORTEX; BRAIN; STROKE; RTMS
AB In the last decade transcranial magnetic stimulation (TMS) has been the subject of more than 20,000 original research articles. Despite this popularity, TMS responses are known to be highly variable and this variability can impact on interpretation of research findings. There are no guidelines regarding the factors that should be reported and/or controlled in TMS studies. This study aimed to develop a checklist to be recommended to evaluate the methodology and reporting of studies that use single or paired pulse TMS to study the motor system. A two round international web-based Delphi study was conducted. Panellists rated the importance of a number of subject, methodological and analytical factors to be reported and/or controlled in studies that use single or paired pulse TMS to study the motor system. Twenty-seven items for single pulse studies and 30 items for paired pulse studies were included in the final checklist. Eight items related to subjects (e. g. age, gender), 21 to methodology (e. g. coil type, stimulus intensity) and two to analysis (e. g. size of the unconditioned motor evoked potential). The checklist is recommended for inclusion when submitting manuscripts for publication to ensure transparency of reporting and could also be used to critically appraise previously published work. It is envisaged that factors could be added and deleted from the checklist on the basis of future research. Use of the TMS methodological checklist should improve the quality of data collection and reporting in TMS studies of the motor system. (C) 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
C1 [Chipchase, Lucy; Schabrun, Siobhan; Hodges, Paul] Univ Queensland, NHMRC Ctr Clin Res Excellence Spinal Pain Injury, Brisbane, Qld 4072, Australia.
[Cohen, Leonardo] Natl Inst Neurol Disorders & Stroke, Human Cort Physiol & Neurorehabil Sect, NIH, Bethesda, MD USA.
[Ridding, Michael] Univ Adelaide, Neuromotor Plast & Dev Grp, Robinson Inst, Sch Paediat & Reprod Hlth, Adelaide, SA 5005, Australia.
[Rothwell, John] UCL Inst Neurol, London, England.
[Taylor, Janet] Univ New S Wales, Sydney, NSW 2052, Australia.
[Ziemann, Ulf] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurol, D-72074 Tubingen, Germany.
RP Chipchase, L (reprint author), Univ Queensland, NHMRC Ctr Clin Res Excellence Spinal Pain Injury, Brisbane, Qld 4072, Australia.
EM l.chipchase@uq.edu.au
RI Taylor, Janet/C-9667-2011; Hodges, Paul/B-6578-2008; Schabrun,
Siobhan/F-6925-2010;
OI Taylor, Janet/0000-0001-8976-5162; Hodges, Paul/0000-0002-1206-9107;
Schabrun, Siobhan/0000-0002-9083-3107; Rothwell,
John/0000-0003-1367-6467
FU Intramural NIH HHS [ZIA NS002978-12]
NR 43
TC 48
Z9 48
U1 6
U2 23
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1388-2457
EI 1872-8952
J9 CLIN NEUROPHYSIOL
JI Clin. Neurophysiol.
PD SEP
PY 2012
VL 123
IS 9
BP 1698
EP 1704
DI 10.1016/j.clinph.2012.05.003
PG 7
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 984IR
UT WOS:000307183800008
PM 22647458
ER
PT J
AU Slobounov, S
Sebastianelli, W
Hallett, M
AF Slobounov, Semyon
Sebastianelli, Wayne
Hallett, Mark
TI Residual brain dysfunction observed one year post-mild traumatic brain
injury: Combined EEG and balance study
SO CLINICAL NEUROPHYSIOLOGY
LA English
DT Article
DE EEG; Mild traumatic brain injury; Balance; Center of pressure (COP) area
ID SPORTS-RELATED CONCUSSION; CEREBRAL CONCUSSION; HEAD-INJURIES;
HIGH-SCHOOL; RECOVERY; STABILITY; TASK; OSCILLATIONS; RELIABILITY;
PERFORMANCE
AB Objectives: There is still considerable debate and controversy about whether EEG can be used as a robust clinical tool for assessment of mild traumatic brain injury (MTBI). Nonhomogeneous subject populations, inaccurate assessment of severity of brain injury, time since injury when EEG testing was performed, the lack of EEG research conducted serially and in conjunction with other behavioral measures as injury evolves over time may contribute to the existing controversies. In this study, we implemented a concussion assessment protocol combining a series of EEG and balance measures throughout one year post-injury to document the efficacy of EEG and balance measures as relate to differential recovery of patients suffering from MTBI.
Methods: Three hundred and eighty subjects at risk for MTBI were initially recruited for baseline testing. Forty nine from this initial subjects pool subsequently suffered a single episode of concussive blow and were tested on day 7, 15, 30 days, 6 months and 12 months post-injury. EEGs were recorded while sitting, standing on the force plate and then on a foam base of support with eyes open/closed conditions. EEG alpha power (8-12 Hz) and its percent suppression from sitting to standing postures were computed. The center of pressure (COP) measures were obtained from the force platform and analyzed for eyes open and eyes closed conditions.
Results: Percent alpha power suppression from sitting to standing postural conditions significantly increased in MTBI subjects shortly after the injury (p < 0.01). Percent alpha power suppression significantly correlated with increased area of COP during standing posture with eye closed (r(2) = 0.53, p < 0.01). The magnitude of alpha power suppression predicted the rate of recovery of this measure in sub-acute and chronic phases of injury (r(2) = 0.609, p < 0.01). Finally, 85% of MTBI subjects who showed more than 20% of alpha power suppression in the acute phase of injury did not return to pre-injury status up to 12 months post-injury.
Conclusions: The efficacy of serially implemented EEG measures in conjunction with balance assessment over the course of MTBI evolution to document residual cerebral dysfunction was demonstrated. Specifically, alteration of EEG alpha power dynamics in conjunction with balance data in the acute phase of injury with respect to baseline measures may predict the rate of recovery from a single concussive blow.
Significance: Neurophysiological measures are excellent tools to assess the status and prognosis of patients with MTBI. (C) 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
C1 [Slobounov, Semyon; Sebastianelli, Wayne] Penn State Univ, Dept Kinesiol, University Pk, PA 16802 USA.
[Slobounov, Semyon; Sebastianelli, Wayne] Penn State Univ, HMC, Dept Orthoped & Med Rehabil, University Pk, PA 16802 USA.
[Slobounov, Semyon; Hallett, Mark] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA.
RP Slobounov, S (reprint author), Penn State Univ, Dept Kinesiol, 19 Recreat Bldg, University Pk, PA 16802 USA.
EM sms18@psu.edu
FU National Institutes of Health [RO1 NS056227-01A2]
FX This work was supported by National Institutes of Health Grant RO1
NS056227-01A2 "Identification of Athletes at Risk for Traumatic Brain
Injury".
NR 57
TC 16
Z9 16
U1 2
U2 27
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1388-2457
J9 CLIN NEUROPHYSIOL
JI Clin. Neurophysiol.
PD SEP
PY 2012
VL 123
IS 9
BP 1755
EP 1761
DI 10.1016/j.clinph.2011.12.022
PG 7
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 984IR
UT WOS:000307183800016
PM 22361265
ER
PT J
AU Goetz, KE
Reeves, MJ
Tumminia, SJ
Brooks, BP
AF Goetz, Kerry E.
Reeves, Melissa J.
Tumminia, Santa J.
Brooks, Brian P.
TI eyeGENE(R): a novel approach to combine clinical testing and researching
genetic ocular disease
SO CURRENT OPINION IN OPHTHALMOLOGY
LA English
DT Review
DE biorepository; clinical trials; eyeGENE; genetic testing; patient
registry
ID CONGENITAL AMAUROSIS; MACULAR DEGENERATION; VISUAL FUNCTION; MOUSE
MODEL; LONG-TERM; THERAPY; TRANSPLANTATION; MUTATIONS; SAFETY; CELLS
AB Purpose of review
Molecular genetics is revolutionizing the diagnosis and treatment of inherited eye diseases. The National Eye Institute of the National Institutes of Health (NIH), in an effort to facilitate future basic and clinical research in inherited eye disease, created The National Ophthalmic Disease Genotyping and Phenotyping Network (eyeGENE). This review describes the process and utility of the eyeGENE program as it relates to ophthalmic clinical practice.
Recent findings
Over the last few years, genetic testing of specific genes associated with inherited eye conditions is becoming the standard practice. Vision research and human clinical trials relying on molecular genetic testing of individuals with inherited eye conditions are becoming more common. Eye healthcare professionals must consider the options to assist patients in obtaining genetic testing results and locating trials or studies that may have benefit.
Summary
eyeGENE is a DNA repository and patient registry for inherited eye diseases coupled to phenotypic descriptors and molecular genetic information. Through eyeGENE, healthcare professionals throughout the United States and Canada can obtain Clinical Laboratory Improvement Amendments-certified clinical molecular genetic results on their patients. Researchers may request access to a de-identified database of phenotype and genotype information about eyeGENE participants and DNA aliquots for their research studies. eyeGENE also offers participants the option of being included in a patient registry, whereby they may be re-contacted if an approved clinical study for which they might qualify is offered.
C1 [Goetz, Kerry E.; Brooks, Brian P.] NEI, Ophthalm Genet & Visual Funct Branch, Bethesda, MD 20892 USA.
[Reeves, Melissa J.] NEI, Div Intramural Res, Bethesda, MD 20892 USA.
RP Goetz, KE (reprint author), NEI, Ophthalm Genet & Visual Funct Branch, 10 Ctr Dr,Room 10N226, Bethesda, MD 20892 USA.
EM goetzke@nei.nih.gov
FU Department of Health and Human Services/National Institutes of
Health/National Eye Institute [06-EI-0236, HHS-N-260-2007-00001-C]
FX This study was supported by the Department of Health and Human
Services/National Institutes of Health/National Eye Institute intramural
program under eyeGENE - Protocol 06-EI-0236 which has been funded in
part under Contract No. HHS-N-260-2007-00001-C.
NR 15
TC 7
Z9 8
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-8738
J9 CURR OPIN OPHTHALMOL
JI Curr. Opin. Ophthalmol.
PD SEP
PY 2012
VL 23
IS 5
BP 355
EP 363
DI 10.1097/ICU.0b013e32835715c9
PG 9
WC Ophthalmology
SC Ophthalmology
GA 993PT
UT WOS:000307872700003
PM 22847030
ER
PT J
AU Surh, I
Behl, M
Elmore, SA
Chhabra, RS
AF Surh, Inok
Behl, Mamta
Elmore, Susan A.
Chhabra, Rajendra S.
TI Comparative dermal toxicity of dicyclohexylcarbodiimide and
diisopropylcarbodiimide in rodents
SO CUTANEOUS AND OCULAR TOXICOLOGY
LA English
DT Article
DE Dicyclohexylcarbodiimide; diisopropylcarbodiimide; skin;
carcinogenicity; toxicity; p53; ras
ID TRANSGENIC MOUSE; CONTACT HYPERSENSITIVITY; B6C3F(1) MICE; TG.AC MICE;
SKIN; CARCINOGENESIS; CARBODIIMIDE; DERMATITIS; INITIATION; BIOASSAYS
AB Dicyclohexylcarbodiimide (DCC) and Diisopropylcarbodiimide (DIC) are two representative chemicals in the carbodiimide class of chemicals used in industry as stabilizing agents. There is a potential of dermal exposure to these agents in chemical, pharmaceutical and recombinant DNA industries. The National Toxicology Program conducted a number of animal studies to characterize toxicity and carcinogenicity of DIC and DCC. Dermal administration of DCC and DIC in F344/N rats and B6C3F1 mice for 90-days induced skin irritation at the site of application in a dose-dependent manner. Microscopically, dose-dependent increases in epidermal hyperplasia and chronic inflammation were observed. We further evaluated the effects of dermal exposure of DCC and DIC in p53 haploinsufficient and Tg.AC mouse models. Results revealed the skin as the primary target of DCC and DIC exposure as indicated by dose - dependent skin lesions (hyperplasia, inflammation and necrosis). DCC induced squamous cell papillomas in Tg.AC mice but did not induce any neoplastic lesions in p53 haploinsufficient mice. Dermal application of DIC did not induce any neoplastic lesions in Tg.AC mice and p53 haploinsufficient mice. Based on these studies, it was predicted that DIC would be negative and DCC positive for carcinogenic activity in the traditional two-year bioassay. In the subsequent studies, the carcinogenic potential of DIC only in F344 rats and B6C3F1 mice in a traditional 2-year chronic carcinogenicity bioassay was evaluated by the dermal route. Findings revealed the skin as the major target organ of toxicity in both sexes in rats and in male mice. There were no neoplastic lesions observed in rats or mice with the administration of DIC. In rats, there were clinical signs of toxicity in the highest dose-group which included ataxia, excitability, impaired gait, low muscle tone, abnormal breathing, lethargy, and seizures. This was accompanied by non-neoplastic lesions in the brain and lung only at the highest dose level.
In conclusion, both DIC and DCC are dermal toxicants. DIC did not have any carcinogenic activity in transgenic mouse models or in the traditional NTP two-year carcinogenicity studies in F344 rats and B6C3F1 mice. DCC was positive in the Tg.AC mouse model and likely to be carcinogenic in the 2-year bioassay as well.
C1 [Surh, Inok; Behl, Mamta; Elmore, Susan A.; Chhabra, Rajendra S.] NIEHS, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
RP Chhabra, RS (reprint author), NIEHS, Div Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA.
EM chhabrar@niehs.nih.gov
NR 34
TC 0
Z9 0
U1 0
U2 3
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1556-9527
J9 CUTAN OCUL TOXICOL
JI Cutan. Ocul. Toxicol.
PD SEP
PY 2012
VL 31
IS 3
BP 177
EP 187
DI 10.3109/15569527.2011.629384
PG 11
WC Ophthalmology; Toxicology
SC Ophthalmology; Toxicology
GA 990NC
UT WOS:000307636700001
PM 22060820
ER
PT J
AU Behl, M
Kadiiska, MB
Hejtmancik, MR
Vasconcelos, D
Chhabra, RS
AF Behl, Mamta
Kadiiska, Maria B.
Hejtmancik, Milton R.
Vasconcelos, Daphne
Chhabra, Rajendra S.
TI Subacute oral and dermal toxicity of tert-butyl hydroperoxide in Fischer
F344/N rats and B6C3F1 mice
SO CUTANEOUS AND OCULAR TOXICOLOGY
LA English
DT Article
DE Tert-butyl hydroperoxide; gavage; dermal; toxicity; rats; mice
ID A.T BASE-PAIRS; SALMONELLA-TYPHIMURIUM; LIVER MITOCHONDRIA;
LIPID-PEROXIDATION; OXIDATIVE MUTAGENS; RADICAL PRODUCTION; DNA
METHYLATION; MOUSE SKIN; IN-VITRO; METABOLISM
AB Tert-butyl hydroperoxide (TBHP) is a catalyst frequently used in oxidation and sulfonation reactions in the plastics industry. Since the toxicological evaluation of TBHP remains unknown, the National Toxicology Program (NTP) designed studies to characterize and compare TBHP toxicity by the dermal and oral (gavage) routes in male and female Fischer 344 rats and B6C3F1 mice in 14-day exposures. Rats and mice were administered TBHP at 22, 44, 88, 176 or 352 mg/kg in 0.5% aqueous methylcellulose for the gavage studies. In the dermal studies, mice were administered the same doses as above, while rats were administered four doses (22, 44, 88, 176 mg/kg) in 50% aqueous acetone. Results from the gavage studies revealed treatment-related decreases in survival in male rats and body weights in both male and female rats in the 352 mg/kg group. Clinical signs included post-treatment lethargy, thinness, abnormal breathing, ruffled fur, and/or ataxia which occurred sporadically. The male mice showed a statistically significant decrease in body weight in the 44, 88, 176, and 352 mg/kg groups. The major target organs of toxicity were the forestomach in male and female rats and mice, and the esophagus in male and female rats and in male mice. In addition, there was an increase in the absolute and relative liver weight in female mice with hepatocellular hypertrophy in the top-dose group only. Results from spin trapping experiments revealed the presence of electron paramagnetic resonance signals from radical adducts in the blood and organic extracts of the liver and kidneys of rats treated by gavage with 176 mg/kg TBHP, suggesting the involvement of free-radical generation. The no observed adverse effect level (NOAEL) was considered to be 22 mg/kg in rats and male mice, and 44 mg/kg in female mice. In the dermal studies, there was no effect on survival, body weight, or organ weights in either rats or mice. TBHP administration at the site of application resulted in dermal irritation, hyperkeratosis, hyperplasia, and/or inflammation of the epidermis and inflammation of the dermis at 176 mg/kg and above in male and female rats. Dermal irritation at the site of application was noted in all the mice exposed to 352 mg/kg TBHP. Histopathological lesions in the epidermis and dermis were seen in the 88-352 mg/kg males and in the 176-352 mg/kg females. The NOAEL was found to be 88 mg/kg for male rats and female mice, and 44 mg/kg for female rats and male mice. In conclusion, these studies demonstrate that TBHP is metabolized to free radicals and is a contact irritant affecting skin by the dermal route of exposure, and forestomach and esophagus by oral administration. There was no evidence of systemic absorption by the dermal route of exposure based on lack of pathological findings (Supported by National Institute of Environmental Health Sciences Contract No. N01-ES-65406).
C1 [Behl, Mamta; Chhabra, Rajendra S.] NIEHS, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Kadiiska, Maria B.] NIEHS, Lab Toxicol & Pharmacol, Res Triangle Pk, NC 27709 USA.
[Hejtmancik, Milton R.; Vasconcelos, Daphne] Battelle Mem Inst, Columbus, OH 43201 USA.
RP Chhabra, RS (reprint author), NIEHS, Div Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA.
EM chhabrar@niehs.nih.gov
FU National Institute of Environmental Health Sciences [N01-ES-65406]
FX Supported by National Institute of Environmental Health Sciences
Contract No. N01-ES-65406.
NR 42
TC 1
Z9 1
U1 1
U2 4
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1556-9527
J9 CUTAN OCUL TOXICOL
JI Cutan. Ocul. Toxicol.
PD SEP
PY 2012
VL 31
IS 3
BP 204
EP 213
DI 10.3109/15569527.2011.641194
PG 10
WC Ophthalmology; Toxicology
SC Ophthalmology; Toxicology
GA 990NC
UT WOS:000307636700005
PM 22369679
ER
PT J
AU Florez, JC
Jablonski, KA
Taylor, A
Mather, K
Horton, E
White, NH
Barrett-Connor, E
Knowler, WC
Shuldiner, AR
Pollin, TI
AF Florez, Jose C.
Jablonski, Kathleen A.
Taylor, Andrew
Mather, Kieren
Horton, Edward
White, Neil H.
Barrett-Connor, Elizabeth
Knowler, William C.
Shuldiner, Alan R.
Pollin, Toni I.
CA Diabet Prevention Program Res Grp
TI The C Allele of ATM rs11212617 Does Not Associate With Metformin
Response in the Diabetes Prevention Program
SO DIABETES CARE
LA English
DT Article
ID LIFE-STYLE INTERVENTION; EUROPEAN ASSOCIATION; CONSENSUS ALGORITHM;
MEDICAL-MANAGEMENT; STATEMENT; GLUCOSE; HYPERGLYCEMIA; ADJUSTMENT;
INITIATION; MELLITUS
AB OBJECTIVE-The C allele at the rs11212617 polymorphism in the ataxia-telangiectasia-mutated (ATM) gene has been associated with greater clinical response to metformin in people with type 2 diabetes. We tested whether this variant modified the effect of metformin in the Diabetes Prevention Program (DPP), in which metformin reduced diabetes incidence by 31% in volunteers with impaired glucose tolerance.
RESEARCH DESIGN AND METHODS-We genotyped rs11212617 in 2,994 DPP participants and analyzed its effects on diabetes incidence and related traits.
RESULTS-Contrary to expectations, C carriers enjoyed no preventive advantage on metformin ; their hazard ratio, compared with A carriers, was 1.17 ([95% CI 0.96-1.42], P = 0.13) under metformin. There were no significant differences by genotype in metformin's effects on insulin sensitivity, fasting glucose, glycated hemoglobin, or disposition index.
CONCLUSIONS-The reported association of rs11212617 with metformin response was not confirmed for diabetes prevention or for effects on relevant physiologic parameters in the DPP.
C1 [Florez, Jose C.; Taylor, Andrew] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Florez, Jose C.; Taylor, Andrew] Massachusetts Gen Hosp, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA.
[Florez, Jose C.; Taylor, Andrew] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Florez, Jose C.; Horton, Edward] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Jablonski, Kathleen A.] George Washington Univ, Biostat Ctr, Dept Epidemiol & Biostat, Rockville, MD USA.
[Mather, Kieren] Indiana Univ Sch Med, Div Endocrinol & Metab, Dept Med, Indianapolis, IN USA.
[Horton, Edward] Joslin Diabet Ctr, Sect Clin Behav & Outcomes Res, Boston, MA 02215 USA.
[White, Neil H.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA.
[White, Neil H.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
[Barrett-Connor, Elizabeth] Univ Calif San Diego, Dept Family Med, San Diego, CA 92103 USA.
[Knowler, William C.] NIDDKD, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA.
[Shuldiner, Alan R.; Pollin, Toni I.] Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
[Shuldiner, Alan R.; Pollin, Toni I.] Univ Maryland, Sch Med, Program Genet & Genom Med, Baltimore, MD 21201 USA.
RP Florez, JC (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
EM jcflorez@partners.org
RI Altshuler, David/A-4476-2009; de Bakker, Paul/B-8730-2009; Uwaifo,
Gabriel/M-2361-2016;
OI Altshuler, David/0000-0002-7250-4107; de Bakker,
Paul/0000-0001-7735-7858; Uwaifo, Gabriel/0000-0002-6962-9304; Franks,
Paul/0000-0002-0520-7604
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; Eunice Kennedy Shriver National
Institute of Child Health and Human Development; Office of Research on
Women's Health; Centers for Disease Control and Prevention; American
Diabetes Association; T.I.P. McKesson BioServices Corp.; Matthews Media
Group, Inc.; Henry M. Jackson Foundation; National Institute on Aging;
[R01-DK-072041]
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, including collection, management, analysis, and
interpretation of the data. 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, and the Department of Veterans Affairs 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 Eunice Kennedy Shriver National Institute of Child
Health and Human Development, the National Institute on Aging, the
Office of Research on Women's Health, the Centers for Disease Control
and Prevention, and the American Diabetes Association. This research was
also supported, in part, by the intramural research program of the NIDDK
and Grant R01-DK-072041 to J.C.F., K.A.J., A.R.S., and T.I.P. McKesson
BioServices Corp., Matthews Media Group, Inc., and the Henry M. Jackson
Foundation provided support services under subcontract with the
coordinating center.
NR 13
TC 22
Z9 22
U1 0
U2 3
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD SEP
PY 2012
VL 35
IS 9
BP 1864
EP 1867
DI 10.2337/dc11-2301
PG 4
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 998XG
UT WOS:000308273100011
PM 22751958
ER
PT J
AU Rutter, MK
Massaro, JM
Hoffmann, U
O'Donnell, CJ
Fox, CS
AF Rutter, Martin K.
Massaro, Joseph M.
Hoffmann, Udo
O'Donnell, Christopher J.
Fox, Caroline S.
TI Fasting Glucose, Obesity, and Coronary Artery Calcification in
Community-Based People Without Diabetes
SO DIABETES CARE
LA English
DT Article
ID INTIMA-MEDIA THICKNESS; SERVICES TASK-FORCE; RISK-FACTORS; METABOLIC
SYNDROME; HEART-DISEASE; CARDIOVASCULAR-DISEASE; SCIENTIFIC STATEMENT;
ASYMPTOMATIC ADULTS; VISCERAL ADIPOSITY; INSULIN-RESISTANCE
AB OBJECTIVE-Our objective was to assess whether impaired fasting glucose (IFG) and obesity are independently related to coronary artery calcification (CAC) in a community-based population.
RESEARCH DESIGN AND METHODS-We assessed CAC using multidetector computed tomography in 3,054 Framingham Heart Study participants (mean [SD] age was 50 [10] years, 49% were women, 29% had IFG, and 25% were obese) free from known vascular disease or diabetes. We tested the hypothesis that IFG (5.6-6.9 mmol/L) and obesity (BMI >= 30 kg/m(2)) were independently associated with high CAC (>90th percentile for age and sex) after adjusting for hypertension, lipids, smoking, and medication.
RESULTS-High-CAC was significantly related to IFG in an age- and sex-adjusted model (odds ratio 1.4 [95% Cl 1.1-1.7], P = 0.002; referent: normal fasting glucose) and after further adjustment for obesity (1.3 [1.0-1.6], P = 0.045). However, IFG was not associated with high CAC in multivariable-adjusted models before (1.2 [0.9-1.4], P = 0.20) or after adjustment for obesity. Obesity was associated with high CAC in age- and sex-adjusted models (1.6 [1.3-2.0], P < 0.001) and in multivariable models that included IFG (1.4 [1.1-1.7], P = 0.005). Multivariableadjusted spline regression models suggested nonlinear relationships linking high CAC with BMI (J-shaped), waist circumference 0-shaped), and fasting glucose.
CONCLUSIONS-In this community-based cohort, CAC was associated with obesity, but not IFG, after adjusting for important confounders. With the increasing worldwide prevalence of obesity and nondiabetic hyperglycemia, these data underscore the importance of obesity in the pathogenesis of CAC.
C1 [Rutter, Martin K.] Univ Manchester, Sch Biomed, Cardiovasc Res Grp, Manchester, Lancs, England.
[Rutter, Martin K.] Natl Hlth Serv Fdn Trust, Manchester Acad Hlth Sci Ctr, Natl Inst Hlth Res,Cent Manchester Biomed Res Ctr, Manchester Diabet Ctr,Cent Manchester Univ Hosp, Manchester, Lancs, England.
[Massaro, Joseph M.] Boston Univ, Dept Math, Boston, MA 02215 USA.
[Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Div Biostat, Boston, MA USA.
[Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA.
[Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[O'Donnell, Christopher J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Cardiol, Boston, MA USA.
[O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Div Intramural Res, Framingham, MA USA.
[O'Donnell, Christopher J.; Fox, Caroline S.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Metab & Diabet, Boston, MA 02115 USA.
RP Rutter, MK (reprint author), Univ Manchester, Sch Biomed, Cardiovasc Res Grp, Manchester, Lancs, England.
EM martin.rutter@manchester.ac.uk
OI Massaro, Joseph/0000-0002-2682-4812; Rutter, Martin/0000-0001-6380-539X
FU National Heart, Lung, and Blood Institute's Framingham Heart Study
(Bethesda, Maryland) [N01-HC-25195]; Higher Education Funding Council
for England (Clinical Senior Lecturer Award); Manchester National
Institute for Health Research Biomedical Research Centre; Manchester
Academic Health Science Centre
FX This work was supported by the National Heart, Lung, and Blood
Institute's Framingham Heart Study (Bethesda, Maryland; N01-HC-25195).
M.K.R. was supported by the Higher Education Funding Council for England
(Clinical Senior Lecturer Award). We also acknowledge support from the
Manchester National Institute for Health Research Biomedical Research
Centre and Manchester Academic Health Science Centre.
NR 34
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U1 0
U2 2
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD SEP
PY 2012
VL 35
IS 9
BP 1944
EP 1950
DI 10.2337/dc11-1950
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 998XG
UT WOS:000308273100025
PM 22773705
ER
PT J
AU Jusko, TA
Klebanoff, MA
Brock, JW
Longnecker, MP
AF Jusko, Todd A.
Klebanoff, Mark A.
Brock, John W.
Longnecker, Matthew P.
TI In-Utero Exposure to Dichlorodiphenyltrichloroethane and Cognitive
Development Among Infants and School-aged Children
SO EPIDEMIOLOGY
LA English
DT Article
ID POLYCHLORINATED-BIPHENYLS PCBS; HUMAN-MILK; ORGANOCHLORINE PESTICIDES;
SERUM; DDT; NEURODEVELOPMENT; DICHLOROETHENE; TRIGLYCERIDE; COHORT;
BIRTH
AB Background: Dichlorodiphenyltrichloroethane (DDT) continues to be used for control of infectious diseases in several countries. In-utero exposure to DDT and dichlorodiphenyldichloroethylene (DDE) has been associated with developmental and cognitive impairment among children. We examined this association in an historical cohort in which the level of exposure was greater than in previous studies.
Methods: The association of in-utero DDT and DDE exposure with infant and child neurodevelopment was examined in 1100 subjects in the Collaborative Perinatal Project, a prospective birth cohort enrolling pregnant women from 12 study centers in the United States from 1959 to 1965. Maternal DDT and DDE concentrations were measured in archived serum specimens. Infant mental and motor development was assessed at age 8 months using the Bayley Scales of Infant Development, and child cognitive development was assessed at age 7 years, using the Wechsler Intelligence Scale for Children.
Results: Although levels of DDT and DDE were relatively high in this population (median DDT concentration, 8.9 mu g/L; DDE, 24.5 mu g/L), neither were related to Mental or Psychomotor Development scores on the Bayley Scales nor to Full-Scale Intelligence Quotient at 7 years of age. Categorical analyses showed no evidence of dose-response for either maternal DDT or DDE, and estimates of the association between continuous measures of exposure and neurodevelopment were indistinguishable from 0.
Conclusions: Adverse associations were not observed between maternal serum DDT and DDE concentrations and offspring neurodevelopment at 8 months or 7 years in this cohort.
C1 [Jusko, Todd A.; Longnecker, Matthew P.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Klebanoff, Mark A.] Ohio State Univ, Dept Pediat, Coll Med, Columbus, OH 43210 USA.
[Brock, John W.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA.
RP Jusko, TA (reprint author), NIEHS, Epidemiol Branch, POB 12233,MD A3-05,111 TW Alexander Dr,Rall Bldg, Res Triangle Pk, NC 27709 USA.
EM todd.jusko@nih.gov
OI Longnecker, Matthew/0000-0001-6073-5322
FU Intramural Research Programs of the National Institute of Environmental
Health Sciences; National Institute of Child Health and Human
Development, NIH; Centers for Disease Control and Prevention, Department
of Health and Human Services
FX Supported by the Intramural Research Programs of the National Institute
of Environmental Health Sciences and National Institute of Child Health
and Human Development, NIH, and the Centers for Disease Control and
Prevention, Department of Health and Human Services.
NR 35
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Z9 10
U1 4
U2 22
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 2012
VL 23
IS 5
BP 689
EP 698
DI 10.1097/EDE.0b013e31825fb61d
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 989LG
UT WOS:000307560700007
PM 22766752
ER
PT J
AU Fedorko, DP
Drake, SK
Stock, F
Murray, PR
AF Fedorko, D. P.
Drake, S. K.
Stock, F.
Murray, P. R.
TI Identification of clinical isolates of anaerobic bacteria using
matrix-assisted laser desorption ionization-time of flight mass
spectrometry
SO EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES
LA English
DT Article
ID SPECIES IDENTIFICATION; ROUTINE IDENTIFICATION; MYCOBACTERIA
AB We evaluated the use of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) for the rapid identification of anaerobic bacteria that had been isolated from clinical specimens and previously identified by 16s rRNA sequencing. The Bruker Microflex MALDI-TOF instrument with the Biotyper Software was used. We tested 152 isolates of anaerobic bacteria from 24 different genera and 75 different species. A total of 125 isolates (82%) had Biotyper software scores greater than 2.0 and the correct identification to genus and species was made by MALDI-TOF for 120 (79%) of isolates. Of the 12 isolates with a score between 1.8 and 2.0, 2 (17%) organisms were incorrectly identified by MALDI-TOF. Only 15 (10%) isolates had a score less than 1.8 and MALDI-TOF gave the wrong genus and species for four isolates, the correct genus for two isolates, and the correct genus and species for nine isolates. Therefore, we found the Bruker MALDI-TOF MicroFlex LT with an expanded database and the use of bacteria extracts rather than whole organisms correctly identified 130 of 152 (86%) isolates to genus and species when the cut-off for an acceptable identification was a spectrum score a parts per thousand yen1.8.
C1 [Fedorko, D. P.; Stock, F.; Murray, P. R.] NIH, Dept Lab Med, Ctr Clin, Microbiol Serv, Bethesda, MD 20892 USA.
[Drake, S. K.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Fedorko, DP (reprint author), NIH, Dept Lab Med, Ctr Clin, Microbiol Serv, Bldg 10,Rm 2C385,10 Ctr Dr MSC 1508, Bethesda, MD 20892 USA.
EM dfedorko@nih.gov
FU NIH Clinical Center, Department of Laboratory Medicine
FX This research was supported by the Intramural Research Program of the
NIH Clinical Center, Department of Laboratory Medicine.
NR 15
TC 36
Z9 38
U1 0
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0934-9723
J9 EUR J CLIN MICROBIOL
JI Eur. J. Clin. Microbiol. Infect. Dis.
PD SEP
PY 2012
VL 31
IS 9
BP 2257
EP 2262
DI 10.1007/s10096-012-1563-4
PG 6
WC Infectious Diseases; Microbiology
SC Infectious Diseases; Microbiology
GA 988TU
UT WOS:000307514400022
PM 22371295
ER
PT J
AU Foley, TL
Simeonov, A
AF Foley, Timothy L.
Simeonov, Anton
TI Targeting iron assimilation to develop new antibacterials
SO EXPERT OPINION ON DRUG DISCOVERY
LA English
DT Review
DE antibacterial; antibiotic; chelation therapy; high-throughput screening;
iron assimilation; siderophore
ID UROPATHOGENIC ESCHERICHIA-COLI; IN-VITRO CHARACTERIZATION;
MYCOBACTERIUM-TUBERCULOSIS; STRUCTURAL-CHARACTERIZATION; SIDEROPHORE
BIOSYNTHESIS; STAPHYLOCOCCUS-AUREUS; PATHOGENIC BACTERIA; GENE-CLUSTER;
BAD BUGS; PSEUDOMONAS-AERUGINOSA
AB Introduction: Since the first application of antibiotics to treat bacterial infections, the development and spread of resistance has been a persistent threat. An ever evolving pipeline of next-generation therapeutics is required for modern medicine to remain one step ahead of pathogens.
Areas covered: This review describes recent efforts to develop drugs that interrupt the assimilation of iron by bacteria: a process that is vital to cellular homeostasis and is not currently targeted by antibiotics used in the clinic. This review also covers the mechanisms by which bacteria acquire iron for their environment, and details efforts to intervene in these processes, using small molecule inhibitors that target key steps in these pathways, with a special emphasis on recent advances published during the 2010 - 2012 period.
Expert opinion: For decades, the routes used by bacteria to assimilate iron from host and environmental settings have been the subject of intense study. While numerous investigations have identified inhibitors of these pathways, many have stopped short of translating the in vitro results to in vivo proof of concept experiments. The extension of preliminary findings in this manner will significantly increase the impact of the field.
C1 [Foley, Timothy L.; Simeonov, Anton] NIH, Natl Ctr Adv Translat Sci, Div Preclin Innovat, Bethesda, MD 20892 USA.
RP Simeonov, A (reprint author), NIH, Natl Ctr Adv Translat Sci, Div Preclin Innovat, 9800 Med Ctr Dr, Bethesda, MD 20892 USA.
EM asimeono@mail.nih.gov
FU Molecular Libraries Initiative of the NIH Common Fund; Intramural
Research Program of NCATS, US National Institutes of Health; US
Government
FX This work was supported, in part, by the Molecular Libraries Initiative
of the NIH Common Fund and the Intramural Research Program of NCATS, US
National Institutes of Health. A. S. is an employee of, and is supported
by the US Government. T. L. F. is a US Government Post-doctoral fellow
and is also supported by the US Government.
NR 92
TC 32
Z9 33
U1 0
U2 28
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 2012
VL 7
IS 9
BP 831
EP 847
DI 10.1517/17460441.2012.708335
PG 17
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 995GT
UT WOS:000307996800007
PM 22812521
ER
PT J
AU O'Doherty, MG
Freedman, ND
Hollenbeck, AR
Schatzkin, A
Abnet, CC
AF O'Doherty, Mark G.
Freedman, Neal D.
Hollenbeck, Albert R.
Schatzkin, Arthur
Abnet, Christian C.
TI A prospective cohort study of obesity and risk of oesophageal and
gastric adenocarcinoma in the NIH-AARP Diet and Health Study
SO GUT
LA English
DT Article
ID BODY-MASS INDEX; GASTROESOPHAGEAL-REFLUX SYMPTOMS; ABDOMINAL OBESITY;
FAT DISTRIBUTION; CANCER-RISK; FOLLOW-UP; ESOPHAGOGASTRIC JUNCTION;
HELICOBACTER-PYLORI; BARRETTS-ESOPHAGUS; CIGARETTE-SMOKING
AB Objective The incidence of oesophageal adenocarcinoma (EAC) has increased rapidly over the past 40 years and accumulating evidence suggests that obesity, as measured by body mass index (BMI), is a major risk factor. It remains unclear whether abdominal obesity is associated with EAC and gastric adenocarcinoma.
Design Cox proportional hazards regression was used to examine associations between overall and abdominal obesity with EAC and gastric adenocarcinoma among 218 854 participants in the prospective NIH-AARP cohort.
Results 253 incident EAC, 191 gastric cardia adenocarcinomas and 125 gastric non-cardia adenocarcinomas accrued to the cohort. Overall obesity (BMI) was positively associated with EAC and gastric cardia adenocarcinoma risk (highest (>= 35 kg/m(2)) vs referent (18.5-<25 kg/m(2)); HR 2.11, 95% CI 1.09 to 4.09 and HR 3.67, 95% CI 2.00 to 6.71, respectively). Waist circumference was also positively associated with EAC and gastric cardia adenocarcinoma risk (highest vs referent; HR 2.01, 95% CI 1.35 to 3.00 and HR 2.22, 95% CI 1.43 to 3.47, respectively), whereas waist-to-hip ratio (WHR) was positively associated with EAC risk only (highest vs referent; HR 1.81, 95% CI 1.24 to 2.64) and persisted in patients with normal BMI (18.5e<25 kg/m(2)). Mutual adjustment of WHR and BMI attenuated both, but did not eliminate the positive associations for either with risk of EAC. In contrast, the majority of the anthropometric variables were not associated with adenocarcinomas of the gastric non-cardia.
Conclusion Overall obesity was associated with a higher risk of EAC and gastric cardia adenocarcinoma, whereas abdominal obesity was found to be associated with increased EAC risk; even in people with normal BMI.
C1 [O'Doherty, Mark G.] Queens Univ Belfast, Ctr Publ Hlth, Canc Epidemiol Hlth Serv Res Grp, Belfast BT12 6BA, Antrim, North Ireland.
[O'Doherty, Mark G.; Freedman, Neal D.; Schatzkin, Arthur; Abnet, Christian C.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Hollenbeck, Albert R.] AARP, Washington, DC USA.
RP O'Doherty, MG (reprint author), Queens Univ Belfast, Royal Victoria Hosp, Ctr Publ Hlth, Canc Epidemiol & Hlth Serv Res Grp, ICS-B Bldg,Grosvenor Rd, Belfast BT12 6BA, Antrim, North Ireland.
EM m.odoherty@qub.ac.uk
RI Abnet, Christian/C-4111-2015; Freedman, Neal/B-9741-2015
OI Abnet, Christian/0000-0002-3008-7843; Freedman, Neal/0000-0003-0074-1098
FU All-Ireland National Cancer Institute Cancer Consortium; Health and
Social Care Research and Development Office (Belfast, Northern Ireland);
Intramural Research Program of the National Institutes of Health,
National Cancer Institute (Bethesda, Maryland, USA)
FX This research was supported (in part) by the All-Ireland National Cancer
Institute Cancer Consortium Joint Research Project in Cancer, supported
by the Health and Social Care Research and Development Office (Belfast,
Northern Ireland) and the Intramural Research Program of the National
Institutes of Health, National Cancer Institute (Bethesda, Maryland,
USA).
NR 49
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Z9 40
U1 0
U2 3
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0017-5749
J9 GUT
JI Gut
PD SEP
PY 2012
VL 61
IS 9
BP 1261
EP 1268
DI 10.1136/gutjnl-2011-300551
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 992WC
UT WOS:000307809900006
PM 22174193
ER
PT J
AU Cornwell, BR
Arkin, N
Overstreet, C
Carver, FW
Grillon, C
AF Cornwell, Brian R.
Arkin, Nicole
Overstreet, Cassie
Carver, Frederick W.
Grillon, Christian
TI Distinct contributions of human hippocampal theta to spatial cognition
and anxiety
SO HIPPOCAMPUS
LA English
DT Article
DE anxiety; hippocampus; magnetoencephalography; spatial cognition; theta
oscillation; virtual navigation
ID MEDIAL PREFRONTAL CORTEX; VIRTUAL WATER MAZE; VENTRAL HIPPOCAMPUS; BRAIN
OSCILLATIONS; HUMAN NAVIGATION; FEAR MEMORY; SENSORIMOTOR INTEGRATION;
DORSAL; RHYTHM; MAGNETOENCEPHALOGRAPHY
AB Current views of the hippocampus assign this structure, and its prominent theta rhythms, a key role in both cognition and affect. We studied this duality of function in humans, where no direct evidence exists. Whole-head magnetoencephalographic (MEG) data were recorded to measure theta activity while healthy participants (N = 25) navigated two virtual Morris water mazes, one in which they risked receiving aversive shocks without warning to induce anxiety and one in which they were safe from shocks. Results showed that threat of shock elevated anxiety level and enhanced navigation performance as compared to the safe condition. MEG source analyses revealed that improved navigation performance during threat was preferentially associated with increased left septal (posterior) hippocampal theta (specifically 48 Hz activity), replicating previous research that emphasizes a predominant role of the septal third of the hippocampus in spatial cognition. Moreover, increased self-reported anxiety during threat was preferentially associated with increased left temporal (anterior) hippocampal theta (specifically 26 Hz activity), consistent with this region's involvement in mediating conditioned and innate fear. Supporting contemporary theory, these findings highlight simultaneous involvement of the human hippocampus in spatial cognition and anxiety, and clarify their distinct correlates. (c) 2012 Wiley Periodicals, Inc.
C1 [Cornwell, Brian R.; Arkin, Nicole; Overstreet, Cassie; Grillon, Christian] NIMH, Sect Neurobiol Fear & Anxiety, NIH, Bethesda, MD 20892 USA.
[Carver, Frederick W.] NIMH, Magnetoencephalog Core Facil, NIH, Bethesda, MD 20892 USA.
RP Cornwell, BR (reprint author), NIMH, Sect Neurobiol Fear & Anxiety, NIH, 15K North Dr,MSC 2670, Bethesda, MD 20892 USA.
EM cornwellb@mail.nih.gov
FU National Institute of Mental Health, National Institutes of Health
FX Grant sponsor: National Institute of Mental Health, National Institutes
of Health.
NR 90
TC 17
Z9 19
U1 2
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1050-9631
J9 HIPPOCAMPUS
JI Hippocampus
PD SEP
PY 2012
VL 22
IS 9
BP 1848
EP 1859
DI 10.1002/hipo.22019
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 996JP
UT WOS:000308082100005
PM 22467298
ER
PT J
AU Aggleton, JP
Wright, NF
Vann, SD
Saunders, RC
AF Aggleton, John P.
Wright, Nicholas F.
Vann, Seralynne D.
Saunders, Richard C.
TI Medial temporal lobe projections to the retrosplenial cortex of the
macaque monkey
SO HIPPOCAMPUS
LA English
DT Article
DE amygdala; cingulate cortex; entorhinal cortex; hippocampus; subiculum
ID SPATIAL WORKING-MEMORY; RHESUS-MONKEY; HIPPOCAMPAL-FORMATION; CINGULATE
CORTEX; CORTICAL PROJECTIONS; MACACA-FASCICULARIS; MAMMILLARY BODIES;
HUMAN NAVIGATION; CEREBRAL-CORTEX; CONNECTIONS
AB The projections to the retrosplenial cortex (areas 29 and 30) from the hippocampal formation, the entorhinal cortex, perirhinal cortex, and amygdala were examined in two species of macaque monkey by tracking the anterograde transport of amino acids. Hippocampal projections arose from the subiculum and presubiculum to terminate principally in area 29. Label was found in layer I and layer III(IV), the former seemingly reflecting both fibers of passage and termination. While the rostral subiculum mainly projects to the ventral retrosplenial cortex, mid and caudal levels of the subiculum have denser projections to both the caudal and dorsal retrosplenial cortex. Appreciable projections to dorsal area 30 [layer III(IV)] were only seen following an extensive injection involving both the caudal subiculum and presubiculum. This same case provided the only example of a light projection from the hippocampal formation to posterior cingulate area 23 (layer III). Anterograde label from the entorhinal cortex injections was typically concentrated in layer I of 29ac, though the very caudal entorhinal cortex appeared to provide more widespread retrosplenial projections. In this study, neither the amygdala nor the perirhinal cortex were found to have appreciable projections to the retrosplenial cortex, although injections in either medial temporal region revealed efferent fibers that pass very close or even within this cortical area. Finally, light projections to area 30V, which is adjacent to the calcarine sulcus, were seen in those cases with rostral subiculum and entorhinal injections. The results reveal a particular affinity between the hippocampal formation and the retrosplenial cortex, and so distinguish areas 29 and 30 from area 23 within the posterior cingulate region. The findings also suggest further functional differences within retrosplenial subregions as area 29 received the large majority of efferents from the subiculum. (c) 2012 Wiley Periodicals, Inc.
C1 [Aggleton, John P.; Wright, Nicholas F.; Vann, Seralynne D.] Cardiff Univ, Sch Psychol, Cardiff CF10 3AT, S Glam, Wales.
[Saunders, Richard C.] NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA.
RP Aggleton, JP (reprint author), Cardiff Univ, Sch Psychol, Pk Pl, Cardiff CF10 3AT, S Glam, Wales.
EM aggleton@cf.ac.uk
OI Vann, Seralynne/0000-0002-6709-8773; Aggleton, John/0000-0002-5573-1308
FU Wolfson Research Merit Award [MRMA09R2]; Wellcome Trust [14945]
FX Grant sponsor: Wolfson Research Merit Award; Grant number: MRMA09R2;
Grant sponsor: Wellcome Trust; Grant number: 14945
NR 59
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Z9 26
U1 2
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1050-9631
J9 HIPPOCAMPUS
JI Hippocampus
PD SEP
PY 2012
VL 22
IS 9
BP 1883
EP 1900
DI 10.1002/hipo.22024
PG 18
WC Neurosciences
SC Neurosciences & Neurology
GA 996JP
UT WOS:000308082100009
PM 22522494
ER
PT J
AU Bjork, JM
Smith, AR
Chen, G
Hommer, DW
AF Bjork, James M.
Smith, Ashley R.
Chen, Gang
Hommer, Daniel W.
TI Mesolimbic recruitment by nondrug rewards in detoxified alcoholics:
Effort anticipation, reward anticipation, and reward delivery
SO HUMAN BRAIN MAPPING
LA English
DT Article
DE reward; impulsivity; nucleus accumbens; ventral striatum; alcoholism;
substance use disorder; instrumental behavior
ID EVENT-RELATED FMRI; DEPENDENT PATIENTS; MAGNETIC-RESONANCE; PERSONALITY;
IMPULSIVITY; ACTIVATION; COCAINE; ADOLESCENTS; ABSTINENCE; DECISION
AB Aberrant sensitivity of incentive neurocircuitry to nondrug rewards has been suggested as either a risk factor for or consequence of drug addiction. Using functional magnetic resonance imaging, we tested whether alcohol-dependent patients (ADP: n = 29) showed altered recruitment of ventral striatal (VS) incentive neurocircuitry compared to controls (n = 23) by: (1) cues to respond for monetary rewards, (2) post-response anticipation of rewards, or (3) delivery of rewards. Using an instrumental task with two-stage presentation of reward-predictive information, subjects saw cues signaling opportunities to win $0, $1, or $10 for responding to a target. Following this response, subjects were notified whether their success would be indicated by a lexical notification (Hit?) or by delivery of a monetary reward (Win?). After a variable interval, subjects then viewed the trial outcome. We found no significant group differences in voxelwise activation by task contrasts, or in signal change extracted from VS. Both ADP and controls showed significant VS and other limbic recruitment by pre-response reward anticipation. In addition, controls also showed VS recruitment by post-response reward-anticipation, and ADP had appreciable subthreshold VS activation. Both groups also showed similar mesolimbic responses to reward deliveries. Across all subjects, a questionnaire measure of hot impulsivity correlated with VS recruitment by post-response anticipation of low rewards and with VS recruitment by delivery of low rewards. These findings indicate that incentive-motivational processing of nondrug rewards is substantially maintained in recovering alcoholics, and that reward-elicited VS recruitment correlates more with individual differences in trait impulsivity irrespective of addiction. Hum Brain Mapp 33:21742188, 2012. Published 2011 Wiley Periodicals, Inc.
C1 [Bjork, James M.] NIDA, Div Clin Neurosci & Behav Res, NIH, Bethesda, MD 20892 USA.
[Smith, Ashley R.; Hommer, Daniel W.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA.
[Chen, Gang] NIMH, Sci & Stat Comp Core, NIH, Bethesda, MD 20892 USA.
RP Bjork, JM (reprint author), NIDA, Div Clin Neurosci & Behav Res, NIH, 6001 Execut Blvd,Room 3157, Bethesda, MD 20892 USA.
EM jbjork@mail.nih.gov
FU National Institute on Alcohol Abuse and Alcoholism
FX Contract grant sponsor: National Institute on Alcohol Abuse and
Alcoholism.
NR 52
TC 17
Z9 17
U1 2
U2 14
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 2012
VL 33
IS 9
BP 2174
EP 2188
DI 10.1002/hbm.21351
PG 15
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 989XB
UT WOS:000307593400013
PM 22281932
ER
PT J
AU Driscoll, I
Beydoun, MA
An, Y
Davatzikos, C
Ferrucci, L
Zonderman, AB
Resnick, SM
AF Driscoll, Ira
Beydoun, May A.
An, Yang
Davatzikos, Christos
Ferrucci, Luigi
Zonderman, Alan B.
Resnick, Susan M.
TI Midlife obesity and trajectories of brain volume changes in older adults
SO HUMAN BRAIN MAPPING
LA English
DT Article
DE BMI; waist circumference; MRI; normal aging; MCI
ID BODY-MASS INDEX; MIDDLE-AGED ADULTS; ALZHEIMERS-DISEASE; UNITED-STATES;
RISK-FACTORS; FOLLOW-UP; WAIST CIRCUMFERENCE; US ADULTS; DEMENTIA;
OVERWEIGHT
AB Although obesity has been linked to structural brain changes, little is known about its associations with the rates of brain atrophy. We examined associations between global (BMI) and central (waist circumference) midlife obesity and subsequent trajectories of regional brain atrophy in 152 individuals [M (age) = 69 +/- 7.8] prospectively followed through the Baltimore Longitudinal Study of Aging; 21 individuals became impaired during follow-up. We report no associations (P > 0.05) between either global or central midlife obesity and subsequent rates of regional brain volume changes against a background of age-related atrophy in older individuals who remained nondemented. When looking at the entire sample, greater decline was observed in the volume of gray matter, precuneus, cingulate and orbito-frontal gyri for globally obese (P < 0.03), even though only data up to the point of dementia diagnosis were included in the analyses (i.e., while still considered clinically normal). Moreover, when trajectories of regional volume changes were examined across the range of BMI and waist circumference values instead of employing a cut-off point to define obesity, a different pattern of results emerged. Overall, our results suggest that midlife obesity may be an important modifier of brain atrophy in individuals who are developing cognitive impairment and dementia, while it has little effect on structural brain integrity in nondemented older adults. Moreover, the discrepancies in findings between studies may be in part due to participant sampling and methodological differences. Hum Brain Mapp 33:2204-2210, 2012. Published 2011 Wiley Periodicals, Inc.
C1 [Driscoll, Ira; Beydoun, May A.; Zonderman, Alan B.; Resnick, Susan M.] NIA, Lab Personal & Cognit, Baltimore, MD 21224 USA.
[An, Yang] MedStar Res Inst, Baltimore, MD USA.
[Davatzikos, Christos] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA.
[Ferrucci, Luigi] NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA.
RP Driscoll, I (reprint author), NIH, Biomed Res Ctr, 251 Bayview Blvd,Suite 100,Room 04B316, Baltimore, MD 21224 USA.
EM driscolli@mail.nih.gov
OI Zonderman, Alan B/0000-0002-6523-4778
FU National Institutes of Health (NIH) [N01-AG-3-2124, R01-AG14971];
Intramural Research Program of the NIH; National Institute on Aging; R&D
(MedStar Research Institute)
FX Contract grant sponsor: National Institutes of Health (NIH); Contract
grant numbers: N01-AG-3-2124, R01-AG14971; Contract grant sponsors:
Intramural Research Program of the NIH; National Institute on Aging; R&D
(MedStar Research Institute).
NR 46
TC 22
Z9 22
U1 0
U2 11
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 2012
VL 33
IS 9
BP 2204
EP 2210
DI 10.1002/hbm.21353
PG 7
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 989XB
UT WOS:000307593400015
PM 22887828
ER
PT J
AU Lou, H
Li, HC
Yeager, M
Im, K
Gold, B
Schneider, TD
Fraumeni, JF
Chanock, SJ
Anderson, SK
Dean, M
AF Lou, Hong
Li, Hongchuan
Yeager, Meredith
Im, Kate
Gold, Bert
Schneider, Thomas D.
Fraumeni, Joseph F., Jr.
Chanock, Stephen J.
Anderson, Stephen K.
Dean, Michael
TI Promoter variants in the MSMB gene associated with prostate cancer
regulate MSMB/NCOA4 fusion transcripts
SO HUMAN GENETICS
LA English
DT Article
ID CELL LUNG-CANCER; ANDROGEN RECEPTOR; BETA-MICROSEMINOPROTEIN; RADICAL
PROSTATECTOMY; FUNCTIONAL-ANALYSIS; HUMAN GENOME; IDENTIFICATION;
COACTIVATOR; PROTEIN; TRANSLOCATIONS
AB Beta-microseminoprotein (MSP)/MSMB is an immunoglobulin superfamily protein synthesized by prostate epithelial cells and secreted into seminal plasma. Variants in the promoter of the MSMB gene have been associated with the risk of prostate cancer (PCa) in several independent genome-wide association studies. Both MSMB and an adjacent gene, NCOA4, are subjected to transcriptional control via androgen response elements. The gene product of NCOA4 interacts directly with the androgen receptor as a co-activator to enhance AR transcriptional activity. Here, we provide evidence for the expression of full-length MSMB-NCOA4 fusion transcripts regulated by the MSMB promoter. The predominant MSMB-NCOA4 transcript arises by fusion of the 5'UTR and exons 1-2 of the MSMB pre-mRNA, with exons 2-10 of the NCOA4 pre-mRNA, producing a stable fusion protein, comprising the essential domains of NCOA4. Analysis of the splice sites of this transcript shows an unusually strong splice acceptor at NCOA4 exon 2 and the presence of Alu repeats flanking the exons potentially involved in the splicing event. Transfection experiments using deletion clones of the promoter coupled with luciferase reporter assays define a core MSMB promoter element located between -27 and -236 of the gene, and a negative regulatory element immediately upstream of the start codon. Computational network analysis reveals that the MSMB gene is functionally connected to NCOA4 and the androgen receptor signaling pathway. The data provide an example of how GWAS-associated variants may have multiple genetic and epigenetic effects.
C1 [Im, Kate; Gold, Bert; Anderson, Stephen K.; Dean, Michael] NCI, Canc & Inflammat Program, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Yeager, Meredith] NCI, Core Genotyping Facil, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Lou, Hong] NCI, Human Genet Sect, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Li, Hongchuan; Anderson, Stephen K.] NCI, Mol Immunol Sect, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Schneider, Thomas D.] Mol Informat Theory Grp, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA.
[Fraumeni, Joseph F., Jr.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Anderson, SK (reprint author), NCI, Canc & Inflammat Program, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21702 USA.
EM andersonst@mail.nih.gov; deanm@mail.nih.gov
OI Schneider, Thomas/0000-0002-9841-1531; Dean, Michael/0000-0003-2234-0631
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research; SAIC-Frederick [NO1-CO-12400]
FX The authors would like to thank Allison Bierly and Wei Tan for critical
reading of the manuscript and helpful comments. The project was
supported in part by the Intramural Research Program of the National
Institutes of Health, National Cancer Institute, Center for Cancer
Research, and from SAIC-Frederick under contract #NO1-CO-12400. The
costs of publication of this article were defrayed in part by the
payment of page charges. This article must therefore be hereby marked
advertisement in accordance with 18 U.S.C. Section 1734 solely to
indicate this fact. 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.
NR 42
TC 8
Z9 9
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
J9 HUM GENET
JI Hum. Genet.
PD SEP
PY 2012
VL 131
IS 9
BP 1453
EP 1466
DI 10.1007/s00439-012-1182-2
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA 988UG
UT WOS:000307515600005
PM 22661295
ER
PT J
AU Verhoeven, VJM
Hysi, PG
Saw, SM
Vitart, V
Mirshahi, A
Guggenheim, JA
Cotch, MF
Yamashiro, K
Baird, PN
Mackey, DA
Wojciechowski, R
Ikram, MK
Hewitt, AW
Duggal, P
Janmahasatian, S
Khor, CC
Fan, Q
Zhou, X
Young, TL
Tai, ES
Goh, LK
Li, YJ
Aung, T
Vithana, E
Teo, YY
Tay, W
Sim, X
Rudan, I
Hayward, C
Wright, AF
Polasek, O
Campbell, H
Wilson, JF
Fleck, BW
Nakata, I
Yoshimura, N
Yamada, R
Matsuda, F
Ohno-Matsui, K
Nag, A
McMahon, G
St Pourcain, B
Lu, Y
Rahi, JS
Cumberland, PM
Bhattacharya, S
Simpson, CL
Atwood, LD
Li, XH
Raffel, LJ
Murgia, F
Portas, L
Despriet, DDG
van Koolwijk, LME
Wolfram, C
Lackner, KJ
Tonjes, A
Magi, R
Lehtimaki, T
Kahonen, M
Esko, T
Metspalu, A
Rantanen, T
Parssinen, O
Klein, BE
Meitinger, T
Spector, TD
Oostra, BA
Smith, AV
de Jong, PTVM
Hofman, A
Amin, N
Karssen, LC
Rivadeneira, F
Vingerling, JR
Eiriksdottir, G
Gudnason, V
Doring, A
Bettecken, T
Uitterlinden, AG
Williams, C
Zeller, T
Castagne, R
Oexle, K
van Duijn, CM
Iyengar, SK
Mitchell, P
Wang, JJ
Hohn, R
Pfeiffer, N
Bailey-Wilson, JE
Stambolian, D
Wong, TY
Hammond, CJ
Klaver, CCW
AF Verhoeven, Virginie J. M.
Hysi, Pirro G.
Saw, Seang-Mei
Vitart, Veronique
Mirshahi, Alireza
Guggenheim, Jeremy A.
Cotch, Mary Frances
Yamashiro, Kenji
Baird, Paul N.
Mackey, David A.
Wojciechowski, Robert
Ikram, M. Kamran
Hewitt, Alex W.
Duggal, Priya
Janmahasatian, Sarayut
Khor, Chiea-Chuen
Fan, Qiao
Zhou, Xin
Young, Terri L.
Tai, E-Shyong
Goh, Liang-Kee
Li, Yi-Ju
Aung, Tin
Vithana, Eranga
Teo, Yik-Ying
Tay, Wanting
Sim, Xueling
Rudan, Igor
Hayward, Caroline
Wright, Alan F.
Polasek, Ozren
Campbell, Harry
Wilson, James F.
Fleck, Brian W.
Nakata, Isao
Yoshimura, Nagahisa
Yamada, Ryo
Matsuda, Fumihiko
Ohno-Matsui, Kyoko
Nag, Abhishek
McMahon, George
St Pourcain, Beate
Lu, Yi
Rahi, Jugnoo S.
Cumberland, Phillippa M.
Bhattacharya, Shomi
Simpson, Claire L.
Atwood, Larry D.
Li, Xiaohui
Raffel, Leslie J.
Murgia, Federico
Portas, Laura
Despriet, Dominiek D. G.
van Koolwijk, Leonieke M. E.
Wolfram, Christian
Lackner, Karl J.
Toenjes, Anke
Maegi, Reedik
Lehtimaki, Terho
Kahonen, Mika
Esko, Tonu
Metspalu, Andres
Rantanen, Taina
Parssinen, Olavi
Klein, Barbara E.
Meitinger, Thomas
Spector, Timothy D.
Oostra, Ben A.
Smith, Albert V.
de Jong, Paulus T. V. M.
Hofman, Albert
Amin, Najaf
Karssen, Lennart C.
Rivadeneira, Fernando
Vingerling, Johannes R.
Eiriksdottir, Guony
Gudnason, Vilmundur
Doering, Angela
Bettecken, Thomas
Uitterlinden, Andre G.
Williams, Cathy
Zeller, Tanja
Castagne, Raphaele
Oexle, Konrad
van Duijn, Cornelia M.
Iyengar, Sudha K.
Mitchell, Paul
Wang, Jie Jin
Hoehn, Rene
Pfeiffer, Norbert
Bailey-Wilson, Joan E.
Stambolian, Dwight
Wong, Tien-Yin
Hammond, Christopher J.
Klaver, Caroline C. W.
TI Large scale international replication and meta-analysis study confirms
association of the 15q14 locus with myopia. The CREAM consortium
SO HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; REFRACTIVE ERROR; PATHOLOGICAL COMPLICATIONS;
SUSCEPTIBILITY LOCUS; OUTDOOR ACTIVITY; COMMON VARIANTS; CHILDREN;
CONNEXIN36; PREVALENCE; POPULATION
AB Myopia is a complex genetic disorder and a common cause of visual impairment among working age adults. Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of European ancestry. Here, we present a confirmation and meta-analysis study in which we assessed whether these two loci are also associated with myopia in other populations. The study population comprised 31 cohorts from the Consortium of Refractive Error and Myopia (CREAM) representing 4 different continents with 55,177 individuals; 42,845 Caucasians and 12,332 Asians. We performed a meta-analysis of 14 single nucleotide polymorphisms (SNPs) on 15q14 and 5 SNPs on 15q25 using linear regression analysis with spherical equivalent as a quantitative outcome, adjusted for age and sex. We calculated the odds ratio (OR) of myopia versus hyperopia for carriers of the top-SNP alleles using a fixed effects meta-analysis. At locus 15q14, all SNPs were significantly replicated, with the lowest P value 3.87 x 10(-12) for SNP rs634990 in Caucasians, and 9.65 x 10(-4) for rs8032019 in Asians. The overall meta-analysis provided P value 9.20 x 10(-23) for the top SNP rs634990. The risk of myopia versus hyperopia was OR 1.88 (95 % CI 1.64, 2.16, P < 0.001) for homozygous carriers of the risk allele at the top SNP rs634990, and OR 1.33 (95 % CI 1.19, 1.49, P < 0.001) for heterozygous carriers. SNPs at locus 15q25 did not replicate significantly (P value 5.81 x 10(-2) for top SNP rs939661). We conclude that common variants at chromosome 15q14 influence susceptibility for myopia in Caucasian and Asian populations world-wide.
C1 [Verhoeven, Virginie J. M.; Ikram, M. Kamran; Despriet, Dominiek D. G.; Vingerling, Johannes R.; Klaver, Caroline C. W.] Erasmus MC, Dept Ophthalmol, NL-3000 CA Rotterdam, Netherlands.
[Verhoeven, Virginie J. M.; Ikram, M. Kamran; Despriet, Dominiek D. G.; van Koolwijk, Leonieke M. E.; Hofman, Albert; Amin, Najaf; Karssen, Lennart C.; Rivadeneira, Fernando; Vingerling, Johannes R.; Uitterlinden, Andre G.; van Duijn, Cornelia M.; Klaver, Caroline C. W.] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands.
[Saw, Seang-Mei; Fan, Qiao; Zhou, Xin; Goh, Liang-Kee; Teo, Yik-Ying; Wong, Tien-Yin] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore.
[Saw, Seang-Mei; Aung, Tin; Vithana, Eranga; Tay, Wanting; Wong, Tien-Yin] Singapore Eye Res Inst, Singapore Natl Eye Ctr, Singapore, Singapore.
[Vitart, Veronique; Hayward, Caroline; Wright, Alan F.] Univ Edinburgh, Med Res Council Human Genet Unit, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.
[Mirshahi, Alireza; Wolfram, Christian; Lackner, Karl J.; Hoehn, Rene; Pfeiffer, Norbert] Johannes Gutenberg Univ Mainz, Dept Ophthalmol, Med Ctr, Mainz, Germany.
[Guggenheim, Jeremy A.] Cardiff Univ, Sch Optometry & Vis Sci, Cardiff, S Glam, Wales.
[Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Yamashiro, Kenji; Nakata, Isao; Yoshimura, Nagahisa] Kyoto Univ, Dept Ophthalmol, Grad Sch Med, Kyoto 606, Japan.
[Baird, Paul N.; Mackey, David A.; Hewitt, Alex W.; Wang, Jie Jin] Univ Melbourne, Ctr Eye Res Australia, Royal Victorian Eye & Ear Hosp, Melbourne, Vic, Australia.
[Mackey, David A.] Univ Western Australia, Ctr Ophthalmol & Visual Sci, Lions Eye Inst, Perth, WA 6009, Australia.
[Wojciechowski, Robert; Duggal, Priya] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Wojciechowski, Robert; Simpson, Claire L.; Bailey-Wilson, Joan E.] NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD USA.
[Ikram, M. Kamran; Aung, Tin; Vithana, Eranga; Wong, Tien-Yin] Natl Univ Singapore, Dept Ophthalmol, Natl Univ Hlth Syst, Singapore 117548, Singapore.
[Janmahasatian, Sarayut; Iyengar, Sudha K.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
[Khor, Chiea-Chuen] Agcy Sci Technol & Res, Genome Inst Singapore, Singapore, Singapore.
[Young, Terri L.; Li, Yi-Ju] Duke Univ, Med Ctr, Ctr Human Genet, Durham, NC 27706 USA.
[Tai, E-Shyong] Natl Univ Singapore, Dept Med, Singapore 117548, Singapore.
[Goh, Liang-Kee] Duke Natl Univ Singapore Grad Med Sch, Singapore, Singapore.
[Teo, Yik-Ying] Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore 117548, Singapore.
[Teo, Yik-Ying; Sim, Xueling] Natl Univ Singapore, Ctr Mol Epidemiol, Singapore 117548, Singapore.
[Rudan, Igor; Campbell, Harry; Wilson, James F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
[Polasek, Ozren] Univ Split, Fac Med, Split, Croatia.
[Fleck, Brian W.] Princess Alexandra Eye Pavil, Edinburgh, Midlothian, Scotland.
[Yamada, Ryo; Matsuda, Fumihiko] Kyoto Univ, Grad Sch Med, Ctr Genom Med, Kyoto, Japan.
[Ohno-Matsui, Kyoko] Tokyo Med & Dent Univ, Dept Ophthalmol & Visual Sci, Tokyo, Japan.
[Lu, Yi] Queensland Inst Med Res, Dept Genet & Populat Hlth, Brisbane, Qld 4006, Australia.
[Atwood, Larry D.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Li, Xiaohui; Raffel, Leslie J.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Murgia, Federico; Portas, Laura] CNR, Inst Populat Genet, Sassari, Italy.
[van Koolwijk, Leonieke M. E.] Rotterdam Eye Hosp, Glaucoma Serv, Rotterdam, Netherlands.
[Lackner, Karl J.] Johannes Gutenberg Univ Mainz, Med Ctr, Inst Clin Chem & Lab Med, Mainz, Germany.
[Toenjes, Anke] Univ Leipzig, Dept Med, Leipzig, Germany.
[Toenjes, Anke] Univ Leipzig, Integrated Res & Treatment Ctr IFB AdiposityDis, Leipzig, Germany.
[Maegi, Reedik; Esko, Tonu; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.
[Lehtimaki, Terho] Tampere Univ Hosp, Dept Clin Chem, Fimlab Labs, FIN-33521 Tampere, Finland.
[Kahonen, Mika] Univ Tampere, Sch Med, Dept Clin Physiol, FIN-33101 Tampere, Finland.
[Kahonen, Mika] Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland.
[Rantanen, Taina] Univ Jyvaskyla, Dept Hlth Sci, Gerontol Res Ctr, Jyvaskyla, Finland.
[Parssinen, Olavi] Cent Hosp Cent Finland, Dept Ophthalmol, Jyvaskyla, Finland.
[Klein, Barbara E.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Sch Med & Publ Hlth, Madison, WI 53706 USA.
[Meitinger, Thomas] German Res Ctr Environm Hlth, Inst Epidemiol 1, Helmholtz Zentrum Munchen, Neuherberg, Germany.
[Meitinger, Thomas; Oexle, Konrad] Tech Univ Munich, Inst Human Genet, Munich, Germany.
[Oostra, Ben A.] Erasmus MC, Dept Clin Genet, NL-3000 CA Rotterdam, Netherlands.
[Smith, Albert V.; Gudnason, Vilmundur] Univ Iceland, Dept Med, Reykjavik, Iceland.
[Smith, Albert V.; Eiriksdottir, Guony; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[de Jong, Paulus T. V. M.] Netherlands Inst Neurosci, Dept Clin & Mol Ophthalmogenet, Amsterdam, Netherlands.
[Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands.
[Bettecken, Thomas] German Res Inst Psychiat, Max Planck Inst Psychiat, Ctr Appl Genotyping, Munich, Germany.
[Zeller, Tanja] Univ Heart Ctr Hamburg, Clin Gen & Intervent Cardiol, Hamburg, Germany.
[Castagne, Raphaele] Univ Paris 06, INSERM, UMRS 937, Paris, France.
[Mitchell, Paul; Wang, Jie Jin] Univ Sydney, Dept Ophthalmol, Ctr Vis Res, Westmead Millennium Inst, Sydney, NSW 2006, Australia.
[Stambolian, Dwight] Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA.
[de Jong, Paulus T. V. M.] Univ Amsterdam, Acad Med Ctr, Dept Ophthalmol, NL-1105 AZ Amsterdam, Netherlands.
[Doering, Angela] German Res Ctr Environm Hlth, Inst Epidemiol 2, Helmholtz Zentrum Munchen, Neuherberg, Germany.
[Williams, Cathy] Univ Bristol, Ctr Child & Adolescent Hlth, Bristol, Avon, England.
[Maegi, Reedik] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[McMahon, George; St Pourcain, Beate] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England.
[Rahi, Jugnoo S.; Cumberland, Phillippa M.] UCL, Inst Child Hlth, Med Res Council Ctr Epidemiol Child Hlth, London, England.
[Rahi, Jugnoo S.; Bhattacharya, Shomi] UCL, Inst Ophthalmol, London, England.
[Cumberland, Phillippa M.] UCL, Ulverscroft Vis Res Grp, London, England.
[Hysi, Pirro G.; Nag, Abhishek; Spector, Timothy D.; Hammond, Christopher J.] Kings Coll London, St Thomas Hosp, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England.
[Castagne, Raphaele] Sch Med, Paris, France.
RP Klaver, CCW (reprint author), Erasmus MC, Dept Ophthalmol, POB 2040, NL-3000 CA Rotterdam, Netherlands.
EM c.c.w.klaver@erasmusmc.nl
RI Rantanen, Taina/O-6579-2016; Mackey, David/H-5340-2014; Hayward,
Caroline/M-8818-2016; Rudan, Igor/I-1467-2012; Hewitt, Alex/D-1936-2013;
Wang, Jie Jin/P-1499-2014; Mitchell, Paul/P-1498-2014; 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; Klaver, Caroline/A-2013-2016; Smith,
Albert/K-5150-2015
OI Hohn, Rene /0000-0003-2870-1469; Baird, Paul/0000-0002-1305-3502; Khor,
Chiea Chuen/0000-0002-1128-4729; Hammond,
Christopher/0000-0002-3227-2620; Ikram, Mohammad
Kamran/0000-0003-0173-9571; Tai, E Shyong/0000-0003-2929-8966; Karssen,
Lennart C./0000-0002-1959-342X; Rantanen, Taina/0000-0002-1604-1945;
Simpson, Claire/0000-0003-2244-7690; Wojciechowski,
Robert/0000-0002-9593-4652; Guggenheim, Jeremy/0000-0001-5164-340X;
Bailey-Wilson, Joan/0000-0002-9153-2920; Cotch, Mary
Frances/0000-0002-2046-4350; Magi, Reedik/0000-0002-2964-6011;
Janmahasatian, Sarayut/0000-0002-4438-8225; Esko,
Tonu/0000-0003-1982-6569; Mackey, David/0000-0001-7914-4709; Hayward,
Caroline/0000-0002-9405-9550; Rudan, Igor/0000-0001-6993-6884; Hewitt,
Alex/0000-0002-5123-5999; Wang, Jie Jin/0000-0001-9491-4898; 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; Smith, Albert/0000-0003-1942-5845
FU Medical Research Council's Health of the Public grant; Wellcome Trust
[083478, 076467]; National Institute for Health Research; Ulverscroft
Vision Research Group; National Institutes of Health [N01AG12100];
National Insitute on Aging; National Eye Institute Intramural Research
Programs [ZIAAG007380, ZI-AEY000401]; Hjartavernd (the Icelandic Heart
Association); Althingi (the Icelandic Parliament); UK Medical Research
Council [4882]; University of Bristol; National Eye Research Centre,
Bristol [SCIAD053]; National Eye Institute/National Institutes of
Health, Bethesda, MD; Bausch & Lomb Inc, Rochester, NY; National Eye
Institute [R01 EY020483]; Intramural Research Program of the National
Human Genome Research Institute, National Institutes of Health, USA;
Australian National Health and Medical Research Council (NHMRC) Enabling
Grant [20042009, 350415]; Clifford Craig Medical Research Trust;
Ophthalmic Research Institute of Australia; American Health Assistance
Foundation; Peggy and Leslie Cranbourne Foundation; Foundation for
Children; Jack Brockhoff Foundation; National Institutes of
Health/National Eye Institute [RO1EY01824601]; Pfizer; Australian NHMRC
Career Development Award; NHMRC; NIH Center for Inherited Disease
Research a; Netherlands Scientific Organization [NWO48005003];
Australian National Health & Medical Research Council (NH& MRC),
Canberra Australia [974159, 211069, 457349, 512423, 475604, 529912];
Centre for Clinical Research Excellence in Translational Clinical
Research in Eye Diseases; NH& MRC research fellowships [358702, 632909,
1028444]; Wellcome Trust, UK; Victorian government; Medical Research
Council (UK); Republic of Croatia Ministry of Science, Education and
Sports [10810803150302]; European Union [LSHGCT2006018947]; NEI
[N01EY22112, N01EY92109]; National Heart, Lung, and Blood Institute
[N02HL64278]; SHARe genotyping; Boston University [N01HC25195]; National
Human Genome Research Institute, NIH, USA; government of Rheinland-Pfalz
("Stiftung Rheinland Pfalz fur Innovation" [AZ961386261733]; Johannes
Gutenberg-University of Mainz; Boehringer Ingelheim; PHILIPS Medical
Systems; National Genome Network "NGFNplus"; Federal Ministry of
Education and Research, Germany [A301GS0833]; Japan Society for the
Promotion of Science, Tokyo [21249084, 22791653]; Italian Ministry of
Education, University and Research [5571DSPAR2002, 718Ric2005];
Netherlands Organisation of Scientific Research (NWO) [Vidi 91796357];
Erasmus Medical Center and Erasmus University, Rotterdam, The
Netherlands; Netherlands Organization for Health Research and
Development (ZonMw); UitZicht; Research Institute for Diseases in the
Elderly; Ministry of Education, Culture and Science; Ministry for
Health, Welfare and Sports; European Commission (DG XII); Municipality
of Rotterdam; Netherlands Genomics Initiative/NWO; Center for Medical
Systems Biology of NGI; Lijf en Leven; M. D. Fonds; Stichting Nederlands
Oogheelkundig; Swart van Essen; Bevordering van Volkskracht;
Blindenhulp; Landelijke Stichting voor Blinden en Slechtzienden;
Rotterdamse Vereniging voor Blindenbelangen; OOG; Algemene Nederlandse
Vereniging ter Voorkoming van Blindheid; Rotterdam Eye Hospital Research
Foundation; Topcon Europe; National Medical Research Council, Singapore
[NMRC 07962003, NMRC 11762008]; Singapore Bio-Medical Research Council
[0612119466, 0913519616]; Interdisciplinary Centre for Clinical Research
at the University of Leipzig; German Diabetes Association; DHFD,
Diabetes Hilfsund Forschungsfonds Deutschland; European Commission under
a Marie Curie Intra-European Fellowship; European Community's Seventh
Framework Programme [FP720072013]; ENGAGE project [HEALTHF42007201413];
European Union MyEuropia Marie Curie Research Training Network; Guide
Dogs for the Blind Association; European Community
[HEALTHF22008201865GEFOS]; ENGAGE [HEALTHF4200720 1413]; US National
Institutes of Health/National Eye Institute [1RO1EY018246]; NIH Center
for Inherited Disease Research; National Institute for Health Research
comprehensive Biomedical Research Centre; St. Thomas' National Health
Service Foundation Trust; King's College London; Academy of Finland
[134309, 126925, 121584, 124282, 129378, 117787, 41071]; Social
Insurance Institution of Finland, Kuopio, Tampere; Turku University
Hospital Medical Funds [9M048]; Juho Vainio Foundation; Paavo Nurmi
Foundation; Finnish Foundation of Cardiovascular Research and Finnish
Cultural Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen
Foundation
FX 1958 British Birth Cohort was funded by the Medical Research Council's
Health of the Public grant (PIs Power and Strachan); the Wellcome Trust
(083478 to J.S.R.); the National Institute for Health Research as
Specialist Biomedical Research Centres partnering respectively with
Great Ormond Street and Moorfields Hospitals; and the Ulverscroft Vision
Research Group.; AGES has been funded by National Institutes of Health
(N01AG12100), the National Insitute on Aging and National Eye Institute
Intramural Research Programs (ZIAAG007380, ZI-AEY000401), Hjartavernd
(the Icelandic Heart Association); and the Althingi (the Icelandic
Parliament). This study acknowledges the contribution of collaborators
on the vision component, Tamara Harris, Lenore Launer, Melissa Garcia,
Susan Corwin, Fridbert Jonasson, Johanna Eyrun Sverrisdottir, Sigurdur
Sigurdsson, and the staff at Hjartavernd.; Core support for ALSPAC was
provided by the UK Medical Research Council (4882); the Wellcome Trust
(076467); the University of Bristol; and for this research specifically
by the National Eye Research Centre, Bristol (SCIAD053). The study
acknowledges Cathy Williams as a guarantor for the contents of this
paper.; The AREDS studies were supported by contracts from National Eye
Institute/National Institutes of Health, Bethesda, MD, with additional
support from Bausch & Lomb Inc, Rochester, NY. The genotyping costs were
supported by the National Eye Institute (R01 EY020483 to D. S.) and some
of the analyses were supported by the Intramural Research Program of the
National Human Genome Research Institute, National Institutes of Health,
USA. AREDS acknowledges Emily Chew and Frederick Ferris, National Eye
Institute, National Institutes of Health, Bethesda, MD; and the Center
for Inherited Disease Research, Baltimore, MD where SNP genotyping was
carried out.; Australian Twins was supported by an Australian National
Health and Medical Research Council (NHMRC) Enabling Grant (20042009,
350415, 2005-2007); Clifford Craig Medical Research Trust; Ophthalmic
Research Institute of Australia; American Health Assistance Foundation;
Peggy and Leslie Cranbourne Foundation; Foundation for Children; Jack
Brockhoff Foundation; National Institutes of Health/National Eye
Institute (RO1EY01824601 (2007-2010)); Pfizer Australia Senior Research
Fellowship (to D. A. M.); and Australian NHMRC Career Development Award
(to S. M.). Genotyping was funded by an NHMRC Medical Genomics Grant and
NIH Center for Inherited Disease Research as part of an National Eye
Institute National Institutes of Health project grant, Australian sample
imputation analyses were carried out on the Genetic Cluster Computer
which is financially supported by the Netherlands Scientific
Organization (NWO48005003). Australian Twins thanks Stuart Macgregor,
Grant W. Montgomery, Nicholas G. Martin, Scott D. Gordon, Dale R.
Nyholt, Sarah E. Medland, Brian P. McEvoy, Margaret J. Wright, Anjali K.
Henders, Megan J. Campbell for ascertaining and processing genotyping
data; Jane MacKinnon, Shayne Brown, Lisa Kearns, Jonathan Ruddle, Paul
Sanfilippo, Sandra Staffieri, Olivia Bigault, Colleen Wilkinson, Jamie
Craig, Yaling Ma, Julie Barbour for assisting with clinical
examinations; and Dr Camilla Day and staff.; The Blue Mountains Eye
Study was supported by the Australian National Health & Medical Research
Council (NH& MRC), Canberra Australia (974159, 211069, 457349, 512423,
475604, 529912); the Centre for Clinical Research Excellence in
Translational Clinical Research in Eye Diseases; NH& MRC research
fellowships (358702, 632909 to J. J. W, 1028444 to P. N. B.); and the
Wellcome Trust, UK as part of Wellcome Trust Case Control Consortium 2
(A Viswanathan, P McGuffin, P Mitchell, F Topouzis, P Foster) for
genotyping costs of the entire BMES population (085475B08Z, 08547508Z,
076113). The Centre for Eye Research Australia receives Operational
Infrastructure Support from the Victorian government. BMES acknowledges
Elena Rochtchina from the Centre for Vision Research, Department of
Ophthalmology and Westmead Millennium Institute University of Sydney
(NSW Australia); John Attia, Rodney Scott, Elizabeth G. Holliday from
the University of Newcastle (Newcastle, NSW Australia); Jing Xie, Maria
Schache and Andrea J. Richardson from the Centre for Eye Research
Australia, Department of Ophthalmology, University of Melbourne; Michael
Inouye, The Walter and Elisa Hall Institute of Medical Research
(Victoria, Australia); Ananth Viswanathan, Moorfields Eye Hospital
(London, UK); Paul J. Foster, NIHR Biomedical Research Centre for
Ophthalmology, UCL Institute of Ophthalmology & Moorfields Eye Hospital
(London); Peter McGuffin, MRC Social Genetic and Developmental
Psychiatry Research Centre, Institute of Psychiatry, King's College
(London, United Kingdom); Fotis Topouzis, Department of Ophthalmology,
School of Medicine, Aristotle University of Thessaloniki, AHEPA Hospital
(Thessaloniki, Greece); Xueling Sim, National University of Singapore;
members of the Wellcome Trust Case Control Consortium 2.; (Membership of
Wellcome Trust Case Control Consortium 2 Peter Donnelly 1,2, Ines
Barroso 3, Jenefer M Blackwell 4, 5, Elvira Bramon 6, Matthew A Brown 7,
Juan P Casas 8, Aiden Corvin 9, Panos Deloukas 3, Audrey Duncanson 10,
Janusz Jankowski 11, Hugh S Markus 12, Christopher G Mathew 13, Colin NA
Palmer 14, Robert Plomin 15, Anna Rautanen 1, Stephen J Sawcer 16,
Richard C Trembath 13, Ananth C Viswanathan 17, Nicholas W Wood 18,
Chris C A Spencer 1, Gavin Band 1, Ce ' line Bellenguez 1, Colin Freeman
1, Garrett Hellenthal 1, Eleni Giannoulatou 1, Matti Pirinen 1, Richard
Pearson 1, Amy Strange 1, Zhan Su 1, Damjan Vukcevic 1, Cordelia
Langford 3, Sarah E Hunt 3, Sarah Edkins 3, Rhian Gwilliam 3, Hannah
Blackburn 3, Suzannah J Bumpstead 3, Serge Dronov 3, Matthew Gillman 3,
Emma Gray 3, Naomi Hammond 3, Alagurevathi Jayakumar 3, Owen T McCann 3,
Jennifer Liddle 3, Simon C Potter 3, Radhi Ravindrarajah 3, Michelle
Ricketts 3, Matthew Waller 3, Paul Weston 3, Sara Widaa 3, Pamela
Whittaker 3 1 Wellcome Trust Centre for Human Genetics, Roosevelt Drive,
Oxford OX3 7LJ, UK; 2 Dept Statistics, University of Oxford, Oxford OX1
3TG, UK; 3 Wellcome Trust Sanger Institute, Wellcome Trust Genome
Campus, Hinxton, Cambridge CB10 1SA, UK; 4 Telethon Institute for Child
Health Research, Centre for Child Health Research, University of Western
Australia, 100 Roberts Road, Subiaco, Western Australia 6008; 5
Cambridge Institute for Medical Research, University of Cambridge School
of Clinical Medicine, Cambridge CB2 0XY, UK; 6 Department of Psychosis
Studies, NIHR Biomedical Research Centre for Mental Health at the
Institute of Psychiatry, King's College London and The South London and
Maudsley NHS Foundation Trust, Denmark Hill, London SE5 8AF, UK; 7
University of Queensland Diamantina Institute, Brisbane, Queensland,
Australia; 8 Dept Epidemiology and Population Health, London School of
Hygiene and Tropical Medicine, London WC1E 7HT and Dept Epidemiology and
Public Health, University College London WC1E 6BT, UK; 9
Neuropsychiatric Genetics Research Group, Institute of Molecular
Medicine, Trinity College Dublin, Dublin 2, Eire; 10 Molecular and
Physiological Sciences, The Wellcome Trust, London NW1 2BE; 11 Centre
for Digestive Diseases, Queen Mary University of London, London E1 2AD,
UK and Digestive Diseases Centre, Leicester Royal Infirmary, Leicester
LE7 7HH, UK and Department of Clinical Pharmacology, Old Road Campus,
University of Oxford, Oxford OX3 7DQ, UK; 12 Clinical Neurosciences, St
George's University of London, London SW17 0RE; 13 King's College London
Dept Medical and Molecular Genetics, School of Medicine, Guy's Hospital,
London SE1 9RT, UK; 14 Biomedical Research Centre, Ninewells Hospital
and Medical School, Dundee DD1 9SY, UK; 15 King's College London Social,
Genetic and Developmental Psychiatry Centre, Institute of Psychiatry,
Denmark Hill, London SE5 8AF, UK; 16 University of Cambridge Dept
Clinical Neurosciences, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK;
17 NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye
Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London
EC1 V 2PD, UK; 18 Dept Molecular Neuroscience, Institute of Neurology,
Queen Square, London WC1 N 3BG, UK.).; The CROATIA studies were funded
by grants from the Medical Research Council (UK) and from the Republic
of Croatia Ministry of Science, Education and Sports (10810803150302);
and the CROATIA- Korcula genotyping was funded by the European Union
framework program 6 project EUROSPAN (LSHGCT2006018947). The CROATIA
studies acknowledges Dr. Goran Bencic, Prof. Zoran Vatavuk, Biljana
Andrijevic Derk, Valentina Lacmanovic Loncar, Kresimir Mandic, Antonija
Mandic, Ivan S. kegro, Jasna Pavicic Astalos., Ivana Merc, Miljenka
Martinovic, Petra Kralj, Tamara Knezevic and Katja Barac-Juretic as well
as the recruitment team from the Croatian Centre for Global Health,
University of Split and the Institute of Anthropological Research in
Zagreb for the ophthalmological data collection; Peter Lichner and the
Helmholtz Zentrum Munchen (Munich, Germany), AROS Applied Biotechnology,
Aarhus, Denmark and the Wellcome Trust Clinical facility (Edinburgh,
United Kingdom) for the SNP genotyping all studies.; ORCADES was
supported by the Chief Scientist Office of the Scottish Government, the
Royal Society, the Medical Research Council Human Genetics Unit and the
European Union framework program 6 EUROSPAN project (LSHGCT2006018947).
ORCADES acknowledges the invaluable contributions of Lorraine Anderson
and the research nurses in Orkney, in particular Margaret Pratt who
performed the eye measurements, as well as the administrative team in
Edinburgh University; and the Wellcome Trust Clinical facility
(Edinburgh, United Kingdom) for DNA extraction; and Peter Lichner and
the Helmholtz Zentrum Munchen (Munich, Germany) for genotyping.; EGCUT
received financing by FP7 grants (201413, 245536); Estonian Government
(SF0180142s08); and the European Union through the European Regional
Development Fund, in the frame of Centre of Excellence in Genomics and
Estonian Research Infrastructure's Roadmap. EGCUT acknowledges Ms. M.
Hass and Mr. V. Soo.; FITSA was supported by ENGAGE (FP7-HEALTH-F4-2007,
201413); the Academy of Finland Center of Excellence in Complex Disease
Genetics (213506, 129680); the Academy of Finland Ageing Programme; and
the Finnish Ministry of Culture and Education and University of
Jyvaskyla. For FITSA the contributions of Emmi Tikkanen, Samuli Ripatti
and Jaakko Kaprio are acknowledged.; Framingham Eye Study was supported
by NEI (N01EY22112, N01EY92109); the National Heart, Lung, and Blood
Institute (N02HL64278) for SHARe genotyping; Boston University
(N01HC25195); and by intramural funds of the National Human Genome
Research Institute, NIH, USA (to R. W. and J.E.B.W.) GHS was funded
through the government of Rheinland-Pfalz ("Stiftung Rheinland Pfalz fur
Innovation" (AZ961386261733); the research programs "Wissen schafft
Zukunft" and "Schwerpunkt Vaskulare Pravention" of the Johannes
Gutenberg-University of Mainz; Boehringer Ingelheim; PHILIPS Medical
Systems; National Genome Network "NGFNplus" by the Federal Ministry of
Education and Research, Germany (A301GS0833).; KORA was financed by the
Helmholtz Center Munich, German Research Center for Environmental
Health; the German Federal Ministry of Education and Research; the State
of Bavaria; the German National Genome Research Network (NGFN-2 and
NGFNPlus) (01GS0823); Munich Center of Health Sciences as part of
LMUinnovativ; the German Research Counsil (DFG) (WI182041 to K. O.); the
genotyping costs were supported by the National Eye Institute (R01
EY020483 to D. S.) and some of the analyses were supported by the
Intramural Research Program of the National Human Genome.; The Kyoto
Study was supported by the Japan Society for the Promotion of Science,
Tokyo (21249084, 22791653).; MESA and MESA SNP Health Association
Resource (SHARe) are conducted and supported by the National Heart,
Lung, and Blood Institute (NHLBI) (N01HC95159, N01HC95169, RR-024156,
N02HL64278 (SHARe genotyping)); the National Institutes of Health
(Intramural Research Program of the National Eye Institute,
(ZI-AEY000403); (R01HL071205 to MESA Family); the Clinical Translational
Science Institute (UL1RR033176); and the Cedars-Sinai General Clinical
Research Center (RR00425). MESA thanks all investigators, especially
Drs. Mary Frances Cotch, Jerome I. Rotter, Ronald Klein, and Tien Y.
Wong in the Eye Working Group, 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.; OGP Talana was supported by grants from the
Italian Ministry of Education, University and Research (5571DSPAR2002,
718Ric2005). OGP Talana thanks the Ogliastra population and the
municipal administrators for their collaboration to the project and for
economic and logistic support.; The Rotterdam Study and ERF were
supported by the Netherlands Organisation of Scientific Research (NWO)
(Vidi 91796357); Erasmus Medical Center and Erasmus University,
Rotterdam, The Netherlands; Netherlands Organization for Health Research
and Development (ZonMw); UitZicht; the Research Institute for Diseases
in the Elderly; the Ministry of Education, Culture and Science; the
Ministry for Health, Welfare and Sports; the European Commission (DG
XII); the Municipality of Rotterdam; the Netherlands Genomics
Initiative/NWO; Center for Medical Systems Biology of NGI; Lijf en
Leven; M. D. Fonds; Henkes Stichting; Stichting Nederlands Oogheelkundig
Onderzoek; Swart van Essen; Bevordering van Volkskracht; Landelijke
Stichting voor Blinden en SlechtziendenBlindenhulp; Landelijke Stichting
voor Blinden en Slechtzienden; Rotterdamse Vereniging voor
Blindenbelangen; OOG; Algemene Nederlandse Vereniging ter Voorkoming van
Blindheid; the Rotterdam Eye Hospital Research Foundation; and Topcon
Europe.; Rotterdam Study and ERF thank Ada Hooghart, Corina Brussee,
Riet Bernaerts-Biskop, Patricia van Hilten, Pascal Arp, Jeanette
Vergeer, Marijn Verkerk and Sander Bervoets. The Singapore studies
(SCORM, SP2, SiMES, SINDI) were supported by the National Medical
Research Council, Singapore (NMRC 07962003, NMRC 11762008), Singapore
Bio-Medical Research Council (0612119466, 0913519616).; The Sorbs study
was supported by the Interdisciplinary Centre for Clinical Research at
the University of Leipzig (B27 to A. T.) from the German Diabetes
Association (to A. T.); the DHFD, Diabetes Hilfsund Forschungsfonds
Deutschland (to A. T.); the European Commission under a Marie Curie
Intra-European Fellowship (to R. M.); the European Community's Seventh
Framework Programme (FP720072013); and ENGAGE project
(HEALTHF42007201413). We thank Michael Stumvoll and Peter Kovacs for the
excellent project coordination and fruitful discussion, furthermore Knut
Krohn (Microarray Core Facility of the Interdisciplinary Centre for
Clinical Research, University of Leipzig) for the genotyping support.;
TwinsUK received funding from the Wellcome Trust; the European Union
MyEuropia Marie Curie Research Training Network; Guide Dogs for the
Blind Association; the European Community's FP7
(HEALTHF22008201865GEFOS); ENGAGE (HEALTHF4200720 1413); the FP-5
GenomEUtwin Project (QLG2CT200201254); US National Institutes of
Health/National Eye Institute (1RO1EY018246); NIH Center for Inherited
Disease Research; the National Institute for Health Research
comprehensive Biomedical Research Centre award to Guy's and St. Thomas'
National Health Service Foundation Trust partnering with King's College
London.; The Young Finns Study was financially supported by the Academy
of Finland (134309 (Eye), 126925, 121584, 124282, 129378 (Salve), 117787
(Gendi), and 41071 (Skidi)); the Social Insurance Institution of
Finland, Kuopio, Tampere; Turku University Hospital Medical Funds (grant
9M048 to T. L.); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish
Foundation of Cardiovascular Research and Finnish Cultural Foundation;
Tampere Tuberculosis Foundation; and Emil Aaltonen Foundation (to T.L.).
NR 38
TC 30
Z9 32
U1 1
U2 17
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
EI 1432-1203
J9 HUM GENET
JI Hum. Genet.
PD SEP
PY 2012
VL 131
IS 9
BP 1467
EP 1480
DI 10.1007/s00439-012-1176-0
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA 988UG
UT WOS:000307515600006
PM 22665138
ER
PT J
AU Liu, YH
Melin, BS
Rajaraman, P
Wang, ZM
Linet, M
Shete, S
Amos, CI
Lau, CC
Scheurer, ME
Tsavachidis, S
Armstrong, GN
Houlston, RS
Hosking, FJ
Claus, EB
Barnholtz-Sloan, J
Lai, R
Il'yasova, D
Schildkraut, J
Sadetzki, S
Johansen, C
Bernstein, JL
Olson, SH
Jenkins, RB
LaChance, D
Vick, NA
Wrensch, M
Davis, F
McCarthy, BJ
Andersson, U
Thompson, PA
Chanock, S
Bondy, ML
AF Liu, Yanhong
Melin, Beatrice S.
Rajaraman, Preetha
Wang, Zhaoming
Linet, Martha
Shete, Sanjay
Amos, Christopher I.
Lau, Ching C.
Scheurer, Michael E.
Tsavachidis, Spiridon
Armstrong, Georgina N.
Houlston, Richard S.
Hosking, Fay J.
Claus, Elizabeth B.
Barnholtz-Sloan, Jill
Lai, Rose
Il'yasova, Dora
Schildkraut, Joellen
Sadetzki, Siegal
Johansen, Christoffer
Bernstein, Jonine L.
Olson, Sara H.
Jenkins, Robert B.
LaChance, Daniel
Vick, Nicholas A.
Wrensch, Margaret
Davis, Faith
McCarthy, Bridget J.
Andersson, Ulrika
Thompson, Patricia A.
Chanock, Stephen
Bondy, Melissa L.
TI Insight in glioma susceptibility through an analysis of 6p22.3,
12p13.33-12.1, 17q22-23.2 and 18q23 SNP genotypes in familial and
non-familial glioma
SO HUMAN GENETICS
LA English
DT Article
ID NERVOUS-SYSTEM; SPORADIC MEDULLOBLASTOMAS; GENETIC EPIDEMIOLOGY;
MESSENGER-RNA; BRAIN-TUMORS; CANCER; ASSOCIATION; PATHWAY; GROWTH;
TUMORIGENESIS
AB The risk of glioma has consistently been shown to be increased twofold in relatives of patients with primary brain tumors (PBT). A recent genome-wide linkage study of glioma families provided evidence for a disease locus on 17q12-21.32, with the possibility of four additional risk loci at 6p22.3, 12p13.33-12.1, 17q22-23.2, and 18q23. To identify the underlying genetic variants responsible for the linkage signals, we compared the genotype frequencies of 5,122 SNPs mapping to these five regions in 88 glioma cases with and 1,100 cases without a family history of PBT (discovery study). An additional series of 84 familial and 903 non-familial cases were used to replicate associations. In the discovery study, 12 SNPs showed significant associations with family history of PBT (P < 0.001). In the replication study, two of the 12 SNPs were confirmed: 12p13.33-12.1 PRMT8 rs17780102 (P = 0.031) and 17q12-21.32 SPOP rs650461 (P = 0.025). In the combined analysis of discovery and replication studies, the strongest associations were attained at four SNPs: 12p13.33-12.1 PRMT8 rs17780102 (P = 0.0001), SOX5 rs7305773 (P = 0.0001) and STKY1 rs2418087 (P = 0.0003), and 17q12-21.32 SPOP rs6504618 (P = 0.0006). Further, a significant gene-dosage effect was found for increased risk of family history of PBT with these four SNPs in the combined data set (P (trend) < 1.0 x 10(-8)). The results support the linkage finding that some loci in the 12p13.33-12.1 and 17q12-q21.32 may contribute to gliomagenesis and suggest potential target genes underscoring linkage signals.
C1 [Liu, Yanhong; Scheurer, Michael E.; Tsavachidis, Spiridon; Armstrong, Georgina N.; Bondy, Melissa L.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
[Lau, Ching C.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
[Rajaraman, Preetha; Wang, Zhaoming; Linet, Martha; Chanock, Stephen] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
[Shete, Sanjay] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA.
[Amos, Christopher I.] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA.
[Houlston, Richard S.; Hosking, Fay J.] Inst Canc Res, Div Genet & Epidemiol, Sutton, Surrey, England.
[Claus, Elizabeth B.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA.
[Claus, Elizabeth B.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA.
[Barnholtz-Sloan, Jill] Case Western Reserve Univ, Sch Med, Case Comprehens Canc Ctr, Cleveland, OH USA.
[Lai, Rose] Columbia Univ, Neurol Inst, New York, NY USA.
[Il'yasova, Dora; Schildkraut, Joellen] Duke Univ, Med Ctr, Dept Community & Family Med, Canc Control & Prevent Program, Durham, NC 27710 USA.
[Sadetzki, Siegal] Chaim Sheba Med Ctr, Canc & Radiat Epidemiol Unit, Gertner Inst, IL-52621 Tel Hashomer, Israel.
[Sadetzki, Siegal] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel.
[Johansen, Christoffer] Danish Canc Soc, Dept Neurol, Copenhagen, Denmark.
[Bernstein, Jonine L.; Olson, Sara H.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
[Jenkins, Robert B.; LaChance, Daniel] Mayo Clin, Ctr Comprehens Canc, Rochester, MN USA.
[Vick, Nicholas A.] N Shore Univ Hlth Syst, Evanston Kellogg Canc Care Ctr, Evanston, IL USA.
[Wrensch, Margaret] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA.
[Davis, Faith; McCarthy, Bridget J.] Univ Illinois, Div Epidemiol & Biostat, Chicago, IL USA.
[Thompson, Patricia A.] Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA.
[Melin, Beatrice S.; Andersson, Ulrika] Umea Univ, Dept Radiat Sci Oncol, Umea, Sweden.
RP Bondy, ML (reprint author), Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
EM mbondy@bcm.edu
OI Scheurer, Michael/0000-0002-8379-6088; Hosking, Fay/0000-0002-1101-039X;
Houlston, Richard/0000-0002-5268-0242
FU National Institutes of Health [5R01 CA119215, 5R01 CA070917,
R01CA52689]; American Brain Tumor Association; National Brain Tumor
Society; Tug McGraw Foundation; Wellcome Trust
FX This work was supported by National Institutes of Health (5R01 CA119215,
5R01 CA070917 and R01CA52689). Additional support was provided by the
American Brain Tumor Association, The National Brain Tumor Society, the
Tug McGraw Foundation and the Wellcome Trust who provided funding for
the parent GWAS. The authors acknowledge the input of the Gliogene
External Advisory Committee. For more information about the Gliogene
Consortium, please refer to the following Web site
http://www.gliogene.org.
NR 34
TC 8
Z9 8
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 2012
VL 131
IS 9
BP 1507
EP 1517
DI 10.1007/s00439-012-1187-x
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 988UG
UT WOS:000307515600009
PM 22688887
ER
PT J
AU Fasching, PA
Pharoah, PDP
Cox, A
Nevanlinna, H
Bojesen, SE
Karn, T
Broeks, A
van Leeuwen, FE
van 't Veer, LJ
Udo, R
Dunning, AM
Greco, D
Aittomaki, K
Blomqvist, C
Shah, M
Nordestgaard, BG
Flyger, H
Hopper, JL
Southey, MC
Apicella, C
Garcia-Closas, M
Sherman, M
Lissowska, J
Seynaeve, C
Huijts, PEA
Tollenaar, RAEM
Ziogas, A
Ekici, AB
Rauh, C
Mannermaa, A
Kataja, V
Kosma, VM
Hartikainen, JM
Andrulis, IL
Ozcelik, H
Mulligan, AM
Glendon, G
Hall, P
Czene, K
Liu, JJ
Chang-Claude, J
Wang-Gohrke, S
Eilber, U
Nickels, S
Doerk, T
Schiekel, M
Bremer, M
Park-Simon, TW
Giles, GG
Severi, G
Baglietto, L
Hooning, MJ
Martens, JWM
Jager, A
Kriege, M
Lindblom, A
Margolin, S
Couch, FJ
Stevens, KN
Olson, JE
Kosei, M
Cross, SS
Balasubramanian, SP
Reed, MWR
Miron, A
John, EM
Winqvist, R
Pylkas, K
Jukkola-Vuorinen, A
Kauppila, S
Burwinkel, B
Marme, F
Schneeweiss, A
Sohn, C
Chenevix-Trench, G
Lambrechts, D
Dieudonne, AS
Hatse, S
van Limbergen, E
Benitez, J
Milne, RL
Zamora, MP
Perez, JIA
Bonanni, B
Peissel, B
Loris, B
Peterlongo, P
Rajaraman, P
Schonfeld, SJ
Anton-Culver, H
Devilee, P
Beckmann, MW
Slamon, DJ
Phillips, KA
Figueroa, JD
Humphreys, MK
Easton, DF
Schmidt, MK
AF Fasching, Peter A.
Pharoah, Paul D. P.
Cox, Angela
Nevanlinna, Heli
Bojesen, Stig E.
Karn, Thomas
Broeks, Annegien
van Leeuwen, Flora E.
van 't Veer, Laura J.
Udo, Renate
Dunning, Alison M.
Greco, Dario
Aittomaki, Kristiina
Blomqvist, Carl
Shah, Mitul
Nordestgaard, Borge G.
Flyger, Henrik
Hopper, John L.
Southey, Melissa C.
Apicella, Carmel
Garcia-Closas, Montserrat
Sherman, Mark
Lissowska, Jolanta
Seynaeve, Caroline
Huijts, Petra E. A.
Tollenaar, Rob A. E. M.
Ziogas, Argyrios
Ekici, Arif B.
Rauh, Claudia
Mannermaa, Arto
Kataja, Vesa
Kosma, Veli-Matti
Hartikainen, Jaana M.
Andrulis, Irene L.
Ozcelik, Hilmi
Mulligan, Anna-Marie
Glendon, Gord
Hall, Per
Czene, Kamila
Liu, Jianjun
Chang-Claude, Jenny
Wang-Gohrke, Shan
Eilber, Ursula
Nickels, Stefan
Doerk, Thilo
Schiekel, Maria
Bremer, Michael
Park-Simon, Tjoung-Won
Giles, Graham G.
Severi, Gianluca
Baglietto, Laura
Hooning, Maartje J.
Martens, John W. M.
Jager, Agnes
Kriege, Mieke
Lindblom, Annika
Margolin, Sara
Couch, Fergus J.
Stevens, Kristen N.
Olson, Janet E.
Kosei, Matthew
Cross, Simon S.
Balasubramanian, Sabapathy P.
Reed, Malcolm W. R.
Miron, Alexander
John, Esther M.
Winqvist, Robert
Pylkas, Katri
Jukkola-Vuorinen, Arja
Kauppila, Saila
Burwinkel, Barbara
Marme, Frederik
Schneeweiss, Andreas
Sohn, Christof
Chenevix-Trench, Georgia
Lambrechts, Diether
Dieudonne, Anne-Sophie
Hatse, Sigrid
van Limbergen, Erik
Benitez, Javier
Milne, Roger L.
Pilar Zamora, M.
Arias Perez, Jose Ignacio
Bonanni, Bernardo
Peissel, Bernard
Loris, Bernard
Peterlongo, Paolo
Rajaraman, Preetha
Schonfeld, Sara J.
Anton-Culver, Hoda
Devilee, Peter
Beckmann, Matthias W.
Slamon, Dennis J.
Phillips, Kelly-Anne
Figueroa, Jonine D.
Humphreys, Manjeet K.
Easton, Douglas F.
Schmidt, Marjanka K.
CA KConFab Investigators
TI The role of genetic breast cancer susceptibility variants as prognostic
factors
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CONFER SUSCEPTIBILITY; COMMON VARIANTS; ATM
GENE; RISK; SURVIVAL; POLYMORPHISMS; LOCUS; WOMEN; CONSORTIUM
AB Recent genome-wide association studies identified 11 single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk. We investigated these and 62 other SNPs for their prognostic relevance. Confirmed BC risk SNPs rs17468277 (CASP8), rs1982073 (TGFB1), rs2981582 (FGFR2), rs13281615 (8q24), rs3817198 (LSP1), rs889312 (MAP3K1), rs3803662 (TOX3), rs13387042 (2q35), rs4973768 (SLC4A7), rs6504950 (COX11) and rs10941679 (5p12) were genotyped for 25 853 BC patients with the available follow-up; 62 other SNPs, which have been suggested as BC risk SNPs by a GWAS or as candidate SNPs from individual studies, were genotyped for replication purposes in subsets of these patients. Cox proportional hazard models were used to test the association of these SNPs with overall survival (OS) and BC-specific survival (BCS). For the confirmed loci, we performed an accessory analysis of publicly available gene expression data and the prognosis in a different patient group. One of the 11 SNPs, rs3803662 (TOX3) and none of the 62 candidate/GWAS SNPs were associated with OS and/or BCS at P0.01. The genotypic-specific survival for rs3803662 suggested a recessive mode of action [hazard ratio (HR) of rare homozygous carriers1.21; 95 CI: 1.091.35, P0.0002 and HR1.29; 95 CI: 1.121.47, P0.0003 for OS and BCS, respectively]. This association was seen similarly in all analyzed tumor subgroups defined by nodal status, tumor size, grade and estrogen receptor. Breast tumor expression of these genes was not associated with prognosis. With the exception of rs3803662 (TOX3), there was no evidence that any of the SNPs associated with BC susceptibility were associated with the BC survival. Survival may be influenced by a distinct set of germline variants from those influencing susceptibility.
C1 [Fasching, Peter A.; Rauh, Claudia; Beckmann, Matthias W.] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Gynecol & Obstet, Univ Breast Ctr,Comprehens Canc Ctr Erlangen Nure, D-91054 Erlangen, Germany.
[Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, D-91054 Erlangen, Germany.
[Fasching, Peter A.; Slamon, Dennis J.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA.
[Pharoah, Paul D. P.; Dunning, Alison M.; Shah, Mitul; Easton, Douglas F.] Univ Cambridge, Dept Oncol, Cambridge, England.
[Pharoah, Paul D. P.; Humphreys, Manjeet K.; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
[Cox, Angela] Univ Sheffield, Inst Canc Studies, CRUK YCR Sheffield Canc Res Ctr, Dept Oncol, Sheffield, S Yorkshire, England.
[Cross, Simon S.] Univ Sheffield, Acad Unit Pathol, Dept Neurosci, Sheffield, S Yorkshire, England.
[Balasubramanian, Sabapathy P.; Reed, Malcolm W. R.] Univ Sheffield, Acad Unit Surg Oncol, CRUK YCR Sheffield Canc Res Ctr, Dept Oncol, Sheffield, S Yorkshire, England.
[Nevanlinna, Heli; Greco, Dario] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland.
[Blomqvist, Carl] Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki, Finland.
[Bojesen, Stig E.; Nordestgaard, Borge G.] Copenhagen Univ Hosp, Herlev Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark.
[Bojesen, Stig E.; Nordestgaard, Borge G.] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Copenhagen, Denmark.
[Flyger, Henrik] Copenhagen Univ Hosp, Herlev Hosp, Dept Breast Surg, Copenhagen, Denmark.
[Karn, Thomas] Goethe Univ Frankfurt, Univ Hosp, Dept Gynecol & Obstet, Frankfurt, Germany.
[Broeks, Annegien; van 't Veer, Laura J.; Schmidt, Marjanka K.] Netherlands Canc Inst, Div Mol Pathol, Amsterdam, Netherlands.
[van Leeuwen, Flora E.; Udo, Renate; Giles, Graham G.; Schmidt, Marjanka K.] Netherlands Canc Inst, Div Psychosocial Res & Epidemiol, Amsterdam, Netherlands.
[Aittomaki, Kristiina] Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki, Finland.
[Southey, Melissa C.] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic, Australia.
[Hopper, John L.; Apicella, Carmel; Giles, Graham G.; Severi, Gianluca; Baglietto, Laura] Univ Melbourne, Melbourne Sch Populat Hlth, Ctr Mol Enviromental Genet & Analyt Epidemiol, Melbourne, Vic, Australia.
[Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, Sutton, Surrey, England.
[Sherman, Mark; Figueroa, Jonine D.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[Seynaeve, Caroline; Jager, Agnes; Kriege, Mieke] Dr Daniel Den Hoed Canc Ctr, Erasmus Med Ctr, Rotterdam Family Canc Clin, Dept Med Oncol, NL-3008 AE Rotterdam, Netherlands.
[Huijts, Petra E. A.; Devilee, Peter] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands.
[Tollenaar, Rob A. E. M.; Hooning, Maartje J.] Leiden Univ, Dept Surg Oncol, Med Ctr, Leiden, Netherlands.
[Devilee, Peter] Leiden Univ, Dept Pathol, Med Ctr, Leiden, Netherlands.
[Ziogas, Argyrios; Anton-Culver, Hoda] Univ Calif Irvine, Sch Med, UCI Ctr Canc Genet Res & Prevent, Irvine, CA 92717 USA.
[Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.] Univ Eastern Finland, Inst Clin Med Pathol & Forens Med, Sch Med, Kuopio, Finland.
[Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.] Univ Eastern Finland, Canc Ctr Eastern Finland, Bioctr Kuopio, Kuopio, Finland.
[Kataja, Vesa] Univ Eastern Finland, Inst Clin Med, Sch Med, Kuopio, Finland.
[Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.] Kuopio Univ Hosp, Dept Clin Pathol, Imaging Ctr, SF-70210 Kuopio, Finland.
[Kataja, Vesa; Glendon, Gord] Kuopio Univ Hosp, Ctr Canc, SF-70210 Kuopio, Finland.
[Andrulis, Irene L.] Canc Care Ontario, Ontario Canc Genet Network, Toronto, ON, Canada.
[Andrulis, Irene L.; Ozcelik, Hilmi; Mulligan, Anna-Marie] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada.
[Andrulis, Irene L.; Ozcelik, Hilmi] Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Fred A Litwin Ctr Canc Genet,Dept Lab Med & Patho, Toronto, ON M5G 1X5, Canada.
[Andrulis, Irene L.; Mulligan, Anna-Marie] Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Fred A Litwin Ctr Canc Genet,Dept Mol Genet, Toronto, ON M5G 1X5, Canada.
St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr, Dept Lab Med, Toronto, ON M5B 1W8, Canada.
[Hall, Per; Czene, Kamila] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
[Margolin, Sara] Karolinska Inst, Dept Oncol & Pathol, Stockholm, Sweden.
[Liu, Jianjun] Genome Inst Singapore, Human Genet Lab, Singapore, Singapore.
[Chang-Claude, Jenny; Eilber, Ursula; Nickels, Stefan] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Burwinkel, Barbara] German Canc Res Ctr, Mol Epidemiol Unit, Heidelberg, Germany.
[Wang-Gohrke, Shan] Univ Ulm, Univ Hosp Ulm, Dept Obstet & Gynecol, Ulm, Germany.
[Doerk, Thilo; Schiekel, Maria; Park-Simon, Tjoung-Won] Hannover Med Sch, Clin Obstet, D-3000 Hannover, Germany.
[Doerk, Thilo; Schiekel, Maria; Park-Simon, Tjoung-Won] Hannover Med Sch, Clin Gynaecol, D-3000 Hannover, Germany.
[Bremer, Michael] Hannover Med Sch, Clin Radiat Oncol, D-3000 Hannover, Germany.
[Severi, Gianluca; Baglietto, Laura] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Martens, John W. M.] Erasmus Univ, Josephine Nefkens Inst, Dept Med Oncol, Med Ctr, Rotterdam, Netherlands.
[Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Stevens, Kristen N.; Olson, Janet E.; Kosei, Matthew] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Miron, Alexander] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA.
[John, Esther M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[John, Esther M.] Stanford Canc Inst, Stanford, CA USA.
[Winqvist, Robert; Pylkas, Katri] Univ Oulu, Dept Clin Genet, Lab Canc Genet, Oulu, Finland.
[Winqvist, Robert; Pylkas, Katri] Univ Oulu, Bioctr Oulu, Oulu, Finland.
[Jukkola-Vuorinen, Arja] Univ Oulu, Dept Oncol, Oulu Univ Hosp, Oulu, Finland.
[Kauppila, Saila] Univ Oulu, Dept Pathol, Oulu Univ Hosp, Oulu, Finland.
[Burwinkel, Barbara; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof] Heidelberg Univ, Univ Heidelberg Hosp, Dept Obstet & Gynecol, Heidelberg, Germany.
[Marme, Frederik; Schneeweiss, Andreas] Univ Heidelberg Hosp, Natl Ctr Tumor Dis, Sect Gynecol Oncol, Heidelberg, Germany.
[Chenevix-Trench, Georgia] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Lambrechts, Diether] Katholieke Univ Leuven VIB, Vesalius Res Ctr, Louvain, Belgium.
[Dieudonne, Anne-Sophie; Hatse, Sigrid; van Limbergen, Erik] Katholieke Univ Leuven, Univ Hosp, Leuven Multidisciplinary Breast Ctr, Louvain, Belgium.
[Benitez, Javier] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Programme, Human Genet Grp, Madrid, Spain.
[Milne, Roger L.] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Programme, Genet & Mol Epidemiol Grp, Madrid, Spain.
[Pilar Zamora, M.] Hosp Univ La Paz, Serv Oncol Med, Madrid, Spain.
[Arias Perez, Jose Ignacio] Hosp Mt Naranco, Serv Cirugia Gen & Especialidades, Oviedo, Spain.
[Bonanni, Bernardo] Ist Europeo Oncol, Div Canc Prevent & Genet, Milan, Italy.
[Loris, Bernard] Ist Europeo Oncol, Dept Expt Oncol, Milan, Italy.
[Peissel, Bernard] Fdn IRCCS Ist Nazl Tumori INT, Dept Prevent & Predict Med, Unit Med Genet, Milan, Italy.
[Peterlongo, Paolo] Fdn IRCCS Ist Nazl Tumori INT, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, Milan, Italy.
[Peterlongo, Paolo] IFOM, Fdn Ist FIRC Oncol Mol, Milan, Italy.
[Rajaraman, Preetha; Schonfeld, Sara J.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Phillips, Kelly-Anne] Peter MacCallum Canc Ctr, Div Canc Med, Melbourne, Vic, Australia.
[Phillips, Kelly-Anne] Univ Melbourne, St Vincents Hosp, Dept Med, Melbourne, Vic 3010, Australia.
RP Fasching, PA (reprint author), Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Gynecol & Obstet, Univ Breast Ctr,Comprehens Canc Ctr Erlangen Nure, D-91054 Erlangen, Germany.
EM peter.fasching@uk-erlangen.de
RI Verdrengh, Evelien/H-4571-2012; Peissel, Bernard/E-8187-2017; Ekici,
Arif/C-3971-2013; Andrulis, Irene/E-7267-2013; Dork, Thilo/J-8620-2012;
karn, t/C-7452-2013; Garcia-Closas, Montserrat /F-3871-2015;
Hartikainen, Jaana/E-6256-2015;
OI Peissel, Bernard/0000-0001-9233-3571; Czene, Kamila/0000-0002-3233-5695;
Cross, Simon/0000-0003-2044-1754; Lissowska,
Jolanta/0000-0003-2695-5799; Phillips, Kelly-Anne/0000-0002-0475-1771;
karn, t/0000-0002-3264-6573; Garcia-Closas, Montserrat
/0000-0003-1033-2650; Greco, Dario/0000-0001-9195-9003; Dunning, Alison
Margaret/0000-0001-6651-7166; Nevanlinna, Heli/0000-0002-0916-2976; Cox,
Angela/0000-0002-5138-1099; Giles, Graham/0000-0003-4946-9099
FU European Community [223175 (HEALTH-F2-2009-223175) (COGS)]; CR-UK
[C1287/A10118, C1287/A12014]; European Union COST programme [BM0606];
Cancer Research UK [C1287/A12014, C490/A10124, C490/A10119]; Cambridge
Biomedical Research Centre; Dutch Cancer Society [NKI 2001-2423, NKI
2007-3839, DDHK 2004-3124, DDHK 2009-4318]; Dutch National Genomics
Initiative; Dutch Biobanking and Biomolecular Resources Research
Infrastructure; National Institutes of Health (NIH) National Cancer
Institute (NCI) [CA122340]; NCI Recovery Act grant [CA122340Z]; NCI
Specialized Program of Research Excellence (SPORE) in breast cancer
[CA116201]; ELAN research program; University Hospital Erlangen;
Deutsche Krebshilfe e. V. [70492]; state of Baden-Wurttemberg through
the Medical Faculty of the University of Ulm [P.685]; Division of Cancer
Epidemiology and Genetics, National Cancer Institute, National
Institutes of Health; Department of Health and Human Services;
Associazione Italiana per la Ricerca sul Cancro [4017]; Fondazione IRCCS
Istituto Nazionale Tumori; 'Stichting tegen Kanker' [232-2008,
196-2010]; Kuopio University Hospital; Cancer Fund of North Savo;
Finnish Cancer Organizations; Academy of Finland; University of Eastern
Finland; Chief Physician Johan Boserup and Lise Boserup Fund; Danish
Medical Research Council; Copenhagen University Hospital; Herlev
Hospital; Rudolf Bartling Foundation; National Breast Cancer Foundation
of Australia; Cancer Australia; National Health and Medical Research
Council of Australia; Queensland Cancer Fund; Cancer Council of New
South Wales; Cancer Council of Victoria; Cancer Council of Tasmania;
Cancer Council of South Australia; Cancer Foundation of Western
Australia; Victorian Health Promotion Foundation (Australia); Breast
Cancer Campaign [2004Nov49]; Yorkshire Cancer Research [S295, S299];
Dietmar-Hopp Foundation; Helmholtz Society; German Cancer Research
Center (DKFZ); Finnish Cancer Foundation; University of Oulu; Oulu
University Hospital; Biocenter Oulu; Helsinki University Central
Hospital Research Fund; Academy of Finland [132473]; Finnish Cancer
Society; Nordic Cancer Union; Sigrid Juselius Foundation; Swedish Cancer
Society; Stockholm Cancer Society; Gustav V Jubilee foundation; Bert von
Kantzow foundation; Agency for Science; Technology and Research of
Singapore (A*STAR); US National Institute of Health (NIH); Susan G.
Komen Breast Cancer Foundation; Marit and Hans Rausings Initiative
Against Breast Cancer; Genome Spain Foundation; Red Tematica de
Investigacion Cooperativa en Cancer; Asociacion Espanola Contra el
Cancer; Fondo de Investigacion Sanitario [PI081583, PI081120]; United
States National Cancer Institute, National Institutes of Health (NIH)
[RFA-CA-06-503]
FX This work was supported by funding from the European Community's Seventh
Framework Programme under grant agreement - 223175
(HEALTH-F2-2009-223175) (COGS). Co-ordination and genotyping in BCAC was
funded by CR-UK (C1287/A10118 and C1287/A12014). Meetings of the BCAC
have been funded by the European Union COST programme (BM0606). D. F. E.
is a Principal Research Fellow of CR-UK. The genotyping was supported by
Cancer Research UK (C490/A10124) and (C1287/A12014). Funding of the
constituent studies and data analysis was supported by the Cambridge
Biomedical Research Centre, Cancer Research UK (C490/A10119). Other
studies have been funded by the Dutch Cancer Society (grants NKI
2001-2423; NKI 2007-3839), the Dutch National Genomics Initiative, the
Dutch Biobanking and Biomolecular Resources Research Infrastructure, the
National Institutes of Health (NIH) National Cancer Institute (NCI)
grant CA122340, NCI Recovery Act grant CA122340Z, NCI Specialized
Program of Research Excellence (SPORE) in breast cancer CA116201, the
ELAN research program, University Hospital Erlangen, the Deutsche
Krebshilfe e. V. (70492), the state of Baden-Wurttemberg through the
Medical Faculty of the University of Ulm (P.685), the Intramural
Research Program of the Division of Cancer Epidemiology and Genetics,
National Cancer Institute, National Institutes of Health, Department of
Health and Human Services, the Associazione Italiana per la Ricerca sul
Cancro (4017) and funds from Italian citizens who allocated the 5/1000
share of their tax payment in support of the Fondazione IRCCS Istituto
Nazionale Tumori, according to Italian laws (INT-Institutional strategic
projects "5x1000"), the 'Stichting tegen Kanker' (232-2008 and
196-2010), the special Government Funding (EVO) of Kuopio University
Hospital grants, Cancer Fund of North Savo, the Finnish Cancer
Organizations, the Academy of Finland and by the strategic funding of
the University of Eastern Finland, the Chief Physician Johan Boserup and
Lise Boserup Fund, the Danish Medical Research Council and Copenhagen
University Hospital, Herlev Hospital, Rudolf Bartling Foundation, the
National Breast Cancer Foundation of Australia, Cancer Australia, the
National Health and Medical Research Council of Australia, the
Queensland Cancer Fund, the Cancer Councils of New South Wales,
Victoria, Tasmania and South Australia, the Cancer Foundation of Western
Australia, the Victorian Health Promotion Foundation (Australia), the
Breast Cancer Campaign (2004Nov49), Yorkshire Cancer Research (S295,
S299 and core funding), the Dietmar-Hopp Foundation, the Helmholtz
Society, the German Cancer Research Center (DKFZ), the Finnish Cancer
Foundation, the Academy of Finland, the University of Oulu, the Oulu
University Hospital, Biocenter Oulu; the Helsinki University Central
Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer
Society, the Nordic Cancer Union and the Sigrid Juselius Foundation; the
Dutch Cancer Society, grants DDHK 2004-3124 and DDHK 2009-4318, the
Swedish Cancer Society, the Stockholm Cancer Society, the Gustav V
Jubilee foundation, the Bert von Kantzow foundation, the Agency for
Science, Technology and Research of Singapore (A*STAR), the US National
Institute of Health (NIH), the Susan G. Komen Breast Cancer Foundation
and Marit and Hans Rausings Initiative Against Breast Cancer, the Genome
Spain Foundation, the Red Tematica de Investigacion Cooperativa en
Cancer and grants from the Asociacion Espanola Contra el Cancer and the
Fondo de Investigacion Sanitario (PI081583 and PI081120).; The ABCFS,
NC-BCFR and OFBCR work was supported by the United States National
Cancer Institute, National Institutes of Health (NIH) under
RFA-CA-06-503 and through cooperative agreements with members of the
Breast Cancer Family Registry (BCFR) and Principal Investigators,
including Cancer Care Ontario (U01 CA69467), Cancer Prevention Institute
of California (U01 CA69417) and University of Melbourne (U01 CA69638).
Samples from the NC-BCFR were processed and distributed by the Coriell
Institute for Medical Research. The content of this manuscript does not
necessarily reflect the views or policies of the National Cancer
Institute or any of the collaborating centers in the BCFR, nor does
mention of trade names, commercial products or organizations imply
endorsement by the US Government or the BCFR.
NR 61
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PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
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JI Hum. Mol. Genet.
PD SEP 1
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DI 10.1093/hmg/dds159
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GA 988PX
UT WOS:000307504100018
PM 22532573
ER
PT J
AU Yoo, TS
Bliss, D
Lowekamp, BC
Chen, DT
Murphy, GE
Narayan, K
Hartnell, LM
Do, T
Subramaniam, S
AF Yoo, Terry S.
Bliss, Donald
Lowekamp, Bradley C.
Chen, David T.
Murphy, Gavin E.
Narayan, Kedar
Hartnell, Lisa M.
Thao Do
Subramaniam, Sriram
TI Visualizing Cells and Humans in 3D Biomedical Image Analysis at
Nanometer and Meter Scales
SO IEEE COMPUTER GRAPHICS AND APPLICATIONS
LA English
DT Article
ID MICROSCOPY
C1 [Yoo, Terry S.; Lowekamp, Bradley C.] US Natl Lib Med, Off High Performance Comp & Commun, Bethesda, MD USA.
[Murphy, Gavin E.] Indiana Univ Bloomington, Cryotransmiss Electron Microscopy Facil, Bloomington, IN USA.
RP Yoo, TS (reprint author), US Natl Lib Med, Off High Performance Comp & Commun, Bethesda, MD USA.
EM tyoo@mail.nih.gov; blissd@mail.nih.gov; blowekamp@mail.nih.gov;
dave@nlm.nih.gov; gamurphy@indiana.edu; narayank@mail.nih.gov;
hartnell@mail.nih.gov; dopt@mail.nih.gov; ss1@nih.gov
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PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA
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EI 1558-1756
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GA 994DJ
UT WOS:000307910800008
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AU Dyer, KD
Sturm, EM
Rosenberg, HF
AF Dyer, Kimberly D.
Sturm, Eva M.
Rosenberg, Helene F.
TI BONE MARROW DERIVED EOSINOPHILS: A TOOL FOR STUDYING THE ROLE OF
EOSINOPHILS IN INNATE IMMUNITY
SO INFLAMMATION RESEARCH
LA English
DT Meeting Abstract
CT 17th International Conference of the Inflammation-Research-Association
CY SEP 09-13, 2012
CL Bolton Landing, NY
SP Inflammat Res Assoc
C1 [Dyer, Kimberly D.; Sturm, Eva M.; Rosenberg, Helene F.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
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PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND
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GA 998FT
UT WOS:000308223600019
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