FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Kawa, S
Onda, M
Ho, M
Kreitman, RJ
Bera, TK
Pastan, I
AF Kawa, Seiji
Onda, Masanori
Ho, Mitchell
Kreitman, Robert J.
Bera, Tapan K.
Pastan, Ira
TI The improvement of an anti-CD22 immunotoxin Conversion to single-chain
and disulfide stabilized form and affinity maturation by alanine scan
SO MABS
LA English
DT Article
DE immunotoxin; HA22; affinity-maturation; alanine scan; V-H/V-L interface
AB HA22-LR is a recombinant immunotoxin for the treatment of B-cell malignancies that contains the Fv portion of an anti-CD22 antibody fused to a functional portion of Pseudomonas exotoxin A. In the present study, we attempted to improve this molecule. First, we produced a single-chain version of HA22-LR (scdsFv-HA22-LR) in which a peptide linker was introduced between the disulfide-linked light and heavy chains to enable production via single fermentation. No difference in cytotoxic activity was observed between scdsFv-HA22-LR and prototype HA22-LR. Next, we attempted to increase the affinity of scdsFv-HA22-LR by using alanine scanning mutagenesis of complementarity determining regions (CDRs) to assess the specific contribution of each CDR residue to the antigen binding. We found that mutation of asparagine 34 in V(L)CDR1, which is located at the V-L/V-H interface, to alanine (N34A) caused a substantial increase in affinity and activity. Estimated K-D values measured by fluorescence-activated cell sorting were lowered by 10-fold: 0.056 nM in the N34A mutant compared to 0.58 nM in wild type (WT). Cell viability assays of CD22-positive B-cell lymphoma and leukemia cell lines showed that the N34A mutant had increased cytotoxicity ranging from similar to 2 (HAL-1, IC50(WT): 2.37 +/- 0.62 ng/ml, IC50(N34A): 1.32 +/- 0.41 ng/ml) to 10 (SUDHL-6, IC50(WT): 0.47 +/- 0.090 ng/ml, IC50(N34A): 0.048 +/- 0.018 ng/ml)-fold compared to WT immunotoxin. The present study suggests that the N34A mutant of scdsFv-HA22-LR could have important consequences in a clinical setting.
C1 [Kawa, Seiji; Onda, Masanori; Ho, Mitchell; Kreitman, Robert J.; Bera, Tapan K.; Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Pastan, I (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM pastani@mail.nih.gov
RI Ho, Mitchell/F-5059-2015
FU NIH, National Cancer Institute, Center for Cancer Research; JSPS
FX We thank Dr. Louis M. Staudt for providing SUDHL-5 and SUDHL-6 cells,
and Dr. Alan Wayne for HAL-1 and Nalm-19 cells. This research was
supported in part by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research and in part by
JSPS Research Fellowship to S.K. for Japanese Biomedical and Behavioral
Research, Japan Society for the Promotion of Science.
NR 41
TC 7
Z9 8
U1 0
U2 4
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 2011
VL 3
IS 5
BP 479
EP 486
DI 10.4161/mabs.3.5.17228
PG 8
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA V29HX
UT WOS:000208740600009
PM 22048691
ER
PT J
AU Dvir-Ginzberg, M
Gabay, O
Oppenhiemer, H
Meir, H
Gagarina, V
Lee, E
Haze, A
Kandel, L
Liebergall, M
AF Dvir-Ginzberg, M.
Gabay, O.
Oppenhiemer, H.
Meir, H.
Gagarina, V.
Lee, E.
Haze, A.
Kandel, L.
Liebergall, M.
TI TNFa INDUCES SIRT1 CLEAVAGE IN HUMAN OSTEOARTHRITIC CHONDROCYTES
SO OSTEOARTHRITIS AND CARTILAGE
LA English
DT Meeting Abstract
C1 [Dvir-Ginzberg, M.; Oppenhiemer, H.; Meir, H.; Haze, A.] Hebrew Univ Jerusalem, Jerusalem, Israel.
[Gabay, O.; Gagarina, V.; Lee, E.] NIAMS, Bethesda, MD USA.
[Kandel, L.; Liebergall, M.] Hadassah Mt Scopus Hosp, Jerusalem, Israel.
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 1063-4584
EI 1522-9653
J9 OSTEOARTHR CARTILAGE
JI Osteoarthritis Cartilage
PD SEP
PY 2011
VL 19
SU 1
MA 198
BP S98
EP S98
PG 1
WC Orthopedics; Rheumatology
SC Orthopedics; Rheumatology
GA V33EH
UT WOS:000209001600221
ER
PT J
AU Gabay, OH
Sanchez, C
Dvir-Ginzberg, M
Gagarina, V
Lee, E
Zaal, KJ
McBurney, MW
Hall, DJ
AF Gabay, O. H.
Sanchez, C.
Dvir-Ginzberg, M.
Gagarina, V.
Lee, E.
Zaal, K. J.
McBurney, M. W.
Hall, D. J.
TI SIRT1-DEFICIENT MICE EXHIBIT AN ALTERED CARTILAGE PHENOTYPE AND UNDERGO
INCREASED CARTILAGE BREAKDOWN AND APOPTOSIS
SO OSTEOARTHRITIS AND CARTILAGE
LA English
DT Meeting Abstract
C1 [Gabay, O. H.; Gagarina, V.; Lee, E.; Zaal, K. J.; Hall, D. J.] NIH, Bethesda, MD 20892 USA.
[Sanchez, C.] Univ Liege, Inst Pathol B23, Bone & Cartilage Res Unit, Liege, Belgium.
[Dvir-Ginzberg, M.] Hebrew Univ Hadassah Kerem, Fac Med Dent, Inst Dent Sci, Lab Cartilage Biol, Jerusalem, Israel.
[McBurney, M. W.] Ottawa Hosp Res Inst, Ottawa, ON, Canada.
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 1063-4584
EI 1522-9653
J9 OSTEOARTHR CARTILAGE
JI Osteoarthritis Cartilage
PD SEP
PY 2011
VL 19
SU 1
MA 60
BP S33
EP S33
PG 1
WC Orthopedics; Rheumatology
SC Orthopedics; Rheumatology
GA V33EH
UT WOS:000209001600083
ER
PT J
AU Hicks, CW
Cui, XZ
Sweeney, DA
Li, Y
Barochia, A
Eichacker, PQ
AF Hicks, Caitlin W.
Cui, Xizhong
Sweeney, Daniel A.
Li, Yan
Barochia, Amisha
Eichacker, Peter Q.
TI The Potential Contributions of Lethal and Edema Toxins to the
Pathogenesis of Anthrax Associated Shock
SO TOXINS
LA English
DT Review
DE anthrax; lethal toxin; edema toxin; shock; myocardial function
ID BACILLUS-ANTHRACIS; PROTECTIVE ANTIGEN; INHALATIONAL ANTHRAX;
CYCLIC-AMP; ADENYLATE-CYCLASE; IN-VIVO; CAPILLARY MORPHOGENESIS;
ESCHERICHIA-COLI; CHOLERA TOXIN; UNITED-STATES
AB Outbreaks of Bacillus anthracis in the US and Europe over the past 10 years have emphasized the health threat this lethal bacteria poses even for developed parts of the world. In contrast to cutaneous anthrax, inhalational disease in the US during the 2001 outbreaks and the newly identified injectional drug use form of disease in the UK and Germany have been associated with relatively high mortality rates. One notable aspect of these cases has been the difficulty in supporting patients once shock has developed. Anthrax bacilli produce several different components which likely contribute to this shock. Growing evidence indicates that both major anthrax toxins may produce substantial cardiovascular dysfunction. Lethal toxin (LT) can alter peripheral vascular function; it also has direct myocardial depressant effects. Edema toxin (ET) may have even more pronounced peripheral vascular effects than LT, including the ability to interfere with the actions of conventional vasopressors. Additionally, ET also appears capable of interfering with renal sodium and water retention. Importantly, the two toxins exert their actions via quite different mechanisms and therefore have the potential to worsen shock and outcome in an additive fashion. Finally, both toxins have the ability to inhibit host defense and microbial clearance, possibly contributing to the very high bacterial loads noted in patients dying with anthrax. This last point is clinically relevant since emerging data has begun to implicate other bacterial components such as anthrax cell wall in the shock and organ injury observed with infection. Taken together, accumulating evidence regarding the potential contribution of LT and ET to anthrax-associated shock supports efforts to develop adjunctive therapies that target both toxins in patients with progressive shock.
C1 [Cui, Xizhong; Li, Yan; Barochia, Amisha; Eichacker, Peter Q.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Hicks, Caitlin W.] Cleveland Clin Lerner Coll Med, Cleveland, OH 44195 USA.
[Hicks, Caitlin W.] Natl Inst Hlth Res Scholar, Howard Hughes Med Inst, NIH, Bethesda, MD 20814 USA.
[Sweeney, Daniel A.] Washington Hosp, Med Intensivist Program, Fremont, CA 94538 USA.
RP Eichacker, PQ (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
EM caitlin.hicks@gmail.com; cxizhong@mail.cc.nih.gov;
danielasweeney@yahoo.com; yli@mail.cc.nih.gov;
braochiaav@mail.cc.nih.gov; peichacker@mail.cc.nih.gov
OI Hicks, Caitlin/0000-0001-7638-1936
NR 86
TC 12
Z9 15
U1 0
U2 5
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 2072-6651
J9 TOXINS
JI Toxins
PD SEP
PY 2011
VL 3
IS 9
BP 1185
EP 1202
DI 10.3390/toxins3091185
PG 18
WC Toxicology
SC Toxicology
GA 995AW
UT WOS:000307979300007
PM 22069762
ER
PT J
AU Toobert, DJ
Strycker, LA
King, DK
Barrera, M
Osuna, D
Glasgow, RE
AF Toobert, Deborah J.
Strycker, Lisa A.
King, Diane K.
Barrera, Manuel, Jr.
Osuna, Diego
Glasgow, Russell E.
TI Long-term outcomes from a multiple-risk-factor diabetes trial for
Latinas: Viva Bien!
SO TRANSLATIONAL BEHAVIORAL MEDICINE
LA English
DT Article
DE Latina; Diabetes; Multiple behavior change Self-management; Randomized
controlled trial
AB Latinas with type 2 diabetes are in need of culturally sensitive interventions to make recommended long-term lifestyle changes and reduce heart disease risk. To test the longer-term (24-month) effects of a previously successful, culturally adapted, multiple-health-behavior-change program, Viva Bien!, 280 Latinas were randomly assigned to usual care or Viva Bien!. Treatment included group meetings to promote a culturally adapted Mediterranean diet, physical activity, supportive resources, problem solving, stress-management practices, and smoking cessation. Viva Bien! participants achieved and maintained some lifestyle improvements from baseline through 24 months, including significant improvements for psychosocial outcomes, fat intake, social-environmental support, body mass index, and hemoglobin A1c. Effects tended to diminish over time. The Viva Bien! multiple-behavior program was effective in improving and maintaining some psychosocial, behavioral, and biological outcomes related to heart health across 24 months for Latinas with type 2 diabetes, a high-risk, underserved population (ClinicalTrials.gov number, NCT00233259).
C1 [Toobert, Deborah J.; Strycker, Lisa A.] Oregon Res Inst, Eugene, OR 97403 USA.
[King, Diane K.] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO 80237 USA.
[Barrera, Manuel, Jr.] Arizona State Univ, Dept Psychol, Tempe, AZ 85287 USA.
[Osuna, Diego] Univ Colorado, Hlth Sci Ctr, Inst Hlth Res, Kaiser Permanente Colorado, Denver, CO 80237 USA.
[Glasgow, Russell E.] NCI, Disseminat & Implementat Sci, Div Canc Control & Populat Sci, Rockville, MD 20852 USA.
RP Toobert, DJ (reprint author), Oregon Res Inst, 1715 Franklin Blvd, Eugene, OR 97403 USA.
EM deborah@ori.org
FU National Heart, Lung, and Blood Institute [R01-HL077120]
FX This research was supported by grant number R01-HL077120 from the
National Heart, Lung, and Blood Institute.
NR 71
TC 20
Z9 20
U1 4
U2 4
PU SPRINGER INTERNATIONAL PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 1869-6716
EI 1613-9860
J9 TRANSL BEHAV MED
JI Transl. Behav. Med.
PD SEP
PY 2011
VL 1
IS 3
BP 416
EP 426
DI 10.1007/s13142-010-0011-1
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA V39LI
UT WOS:000209412100011
PM 22022345
ER
PT J
AU Thomas, DG
Klaessig, F
Harper, SL
Fritts, M
Hoover, MD
Gaheen, S
Stokes, TH
Reznik-Zellen, R
Freund, ET
Klemm, JD
Paik, DS
Baker, NA
AF Thomas, Dennis G.
Klaessig, Fred
Harper, Stacey L.
Fritts, Martin
Hoover, Mark D.
Gaheen, Sharon
Stokes, Todd H.
Reznik-Zellen, Rebecca
Freund, Elaine T.
Klemm, Juli D.
Paik, David S.
Baker, Nathan A.
TI Informatics and standards for nanomedicine technology
SO WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY
LA English
DT Review
ID MEDICAL INFORMATICS; DRUG-DELIVERY; BIOMEDICAL INFORMATICS; IMAGING
INFORMATICS; BIOLOGICAL INTEREST; CHEMICAL ENTITIES; CANCER-THERAPY;
ONTOLOGY; NANOTECHNOLOGY; NANOPARTICLES
AB There are several issues to be addressed concerning the management and effective use of information (or data), generated from nanotechnology studies in biomedical research and medicine. These data are large in volume, diverse in content, and are beset with gaps and ambiguities in the description and characterization of nanomaterials. In this work, we have reviewed three areas of nanomedicine informatics: information resources; taxonomies, controlled vocabularies, and ontologies; and information standards. Informatics methods and standards in each of these areas are critical for enabling collaboration; data sharing; unambiguous representation and interpretation of data; semantic (meaningful) search and integration of data; and for ensuring data quality, reliability, and reproducibility. In particular, we have considered four types of information standards in this article, which are standard characterization protocols, common terminology standards, minimum information standards, and standard data communication (exchange) formats. Currently, because of gaps and ambiguities in the data, it is also difficult to apply computational methods and machine learning techniques to analyze, interpret, and recognize patterns in data that are high dimensional in nature, and also to relate variations in nanomaterial properties to variations in their chemical composition, synthesis, characterization protocols, and so on. Progress toward resolving the issues of information management in nanomedicine using informatics methods and standards discussed in this article will be essential to the rapidly growing field of nanomedicine informatics. (C) 2011 JohnWiley & Sons, Inc. WIREs Nanomed Nanobiotechnol 2011 3 511-532 DOI: 10.1002/wnan.152
C1 [Thomas, Dennis G.; Baker, Nathan A.] Pacific NW Natl Lab, Knowledge Discovery & Informat Grp, Richland, WA 99352 USA.
[Klaessig, Fred] Penn Bio Nano Syst LLC, Doylestown, PA USA.
[Harper, Stacey L.] Oregon State Univ, Sch Chem Biol & Environm Engn, Corvallis, OR 97331 USA.
[Fritts, Martin] NCI, SAIC Frederick, Frederick, MD 21701 USA.
[Hoover, Mark D.] NIOSH, Morgantown, WV USA.
[Gaheen, Sharon] SAIC, Hlth Solut Business Unit, Rockville, MD USA.
[Stokes, Todd H.] Emory Univ, Dept Biomed Engn, Atlanta, GA 30322 USA.
[Stokes, Todd H.] Georgia Tech, Atlanta, GA USA.
[Reznik-Zellen, Rebecca] Univ Massachusetts, Ctr Hierarch Mfg, Amherst, MA 01003 USA.
[Freund, Elaine T.] 3rd Millenium Inc, Waltham, MA USA.
[Klemm, Juli D.] NCI, Ctr Biomed Informat & Informat Technol, Bethesda, MD 20892 USA.
[Paik, David S.] Stanford Univ, Radiol Sci Lab, Stanford, CA 94305 USA.
RP Baker, NA (reprint author), Pacific NW Natl Lab, Knowledge Discovery & Informat Grp, Richland, WA 99352 USA.
EM nathan.baker@pnl.gov
RI Hoover, Mark/I-4201-2012; Baker, Nathan/A-8605-2010;
OI Hoover, Mark/0000-0002-8726-8127; Baker, Nathan/0000-0002-5892-6506;
Reznik-Zellen, Rebecca/0000-0001-9321-8284
FU NIH NCI caBIG(R) Working Group; Pacific Northwest National Laboratory;
NIH [U54 HG004028, U54 CA11934205, U01 NS073457]; Environmental Health
and Sciences Center [P30 ES03850]; EPA [STAR RD-833320]; Safer
Nanomaterials and Nanomanufacturing Initiative of the Oregon Nanoscience
and Microtechnologies Institute [FA8650-05-1-5041]
FX We are grateful to the participants of the caBIG (R) Nanotechnology
Working Group for their comments and contributions to the working group
activities as well as the National Center for Biomedical Ontology for
their support of nanomedicine informatics through the NCBO Bioportal,
Resource Index, and caOBR (R) N.A.B. and D.G.T. acknowledge support from
the NIH NCI caBIG (R) Working Group, Pacific Northwest National
Laboratory HHS sector LDRD funds, as well as NIH grants U54 HG004028,
U54 CA11934205, and U01 NS073457. S.L.H. acknowledges support from NIH
NCI caBIG (R) Working Group, Environmental Health and Sciences Center
P30 ES03850, EPA STAR RD-833320, and the Safer Nanomaterials and
Nanomanufacturing Initiative of the Oregon Nanoscience and
Microtechnologies Institute FA8650-05-1-5041. The views, opinions, and
content in this article are those of the authors and do not necessarily
represent the views, opinions, or policies of their respective employers
or organizations. Mention of company names or products does not
constitute endorsement.
NR 93
TC 17
Z9 17
U1 1
U2 19
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1939-5116
EI 1939-0041
J9 WIRES NANOMED NANOBI
JI Wiley Interdiscip. Rev.-Nanomed. Nanobiotechnol.
PD SEP-OCT
PY 2011
VL 3
IS 5
BP 511
EP 532
DI 10.1002/wnan.152
PG 22
WC Nanoscience & Nanotechnology; Medicine, Research & Experimental
SC Science & Technology - Other Topics; Research & Experimental Medicine
GA 864RX
UT WOS:000298258800007
PM 21721140
ER
PT J
AU Reedy, J
Kirkpatrick, SI
AF Reedy, Jill
Kirkpatrick, Sharon I.
TI The ONQI Is Not a Black Box Author Response
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Letter
C1 [Reedy, Jill; Kirkpatrick, Sharon I.] NCI, Div Canc Control & Populat Sci, Appl Res Program, Risk Factor Monitoring & Methods Branch, Bethesda, MD 20892 USA.
RP Reedy, J (reprint author), NCI, Div Canc Control & Populat Sci, Appl Res Program, Risk Factor Monitoring & Methods Branch, Bethesda, MD 20892 USA.
EM reedyj@mail.nih.gov
NR 5
TC 0
Z9 0
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD SEP
PY 2011
VL 41
IS 3
BP E16
EP E16
DI 10.1016/j.amepre.2011.06.023
PG 1
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 808TW
UT WOS:000294002700002
ER
PT J
AU Carney, JA
Young, WF
Stratakis, CA
AF Carney, J. Aidan
Young, William F., Jr.
Stratakis, Constantine A.
TI Primary Bimorphic Adrenocortical Disease: Cause of Hypercortisolism in
McCune-Albright Syndrome
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE adrenal cortical atrophy; adrenal cortical hyperplasia; Cushing
syndrome; GNAS1 mutation; McCune-Albright syndrome
ID NODULAR ADRENAL-HYPERPLASIA; STIMULATORY G-PROTEIN; CUSHINGS-SYNDROME;
ACTIVATING MUTATIONS; PRECOCIOUS PUBERTY; HYPERTHYROIDISM;
MANIFESTATIONS; PIGMENTATION; DISCORDANT; ENDOCRINE
AB McCune-Albright syndrome (polyostotic fibrous dysplasia, cafe-au-lait skin spots, and precocious puberty) is a genetically mosaic disorder with populations of mutant and normal cells in affected organs. Cushing syndrome, a rare feature of the condition, usually affects infants and is the result of corticotropin-independent primary bilateral adrenal disease, usually interpreted as nodular adrenocortical hyperplasia. In this study of 9 patients with Cushing syndrome and McCune-Albright syndrome, light microscopy revealed a characteristic bimorphic pattern of diffuse and nodular hyperplasia and a distinctive form of cortical atrophy with apparent zona glomerulosa hyperplasia in 8 patients, all very young. The pattern could be explained by the presence of a mosaic distribution of mutant and normal cells in the adrenal glands. The findings are different from those in inherited or other forms of genetically caused Cushing syndrome. The ninth patient, aged 17 years, had an adrenal adenoma and diffuse cortical hyperplasia in each adrenal gland.
C1 [Carney, J. Aidan] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA.
[Young, William F., Jr.] Mayo Clin, Div Endocrinol Diabet Nutr & Metab, Rochester, MN 55905 USA.
[Stratakis, Constantine A.] NICHD, Sect Endocrinol & Genet, NIH, Bethesda, MD USA.
RP Carney, JA (reprint author), Mayo Clin, Dept Lab Med & Pathol, 200 SW 1st St, Rochester, MN 55905 USA.
EM carney.aidan@mayo.edu
FU Mayo Foundation; NIH [Z01HD00064204]
FX J.A.C. received funding from the Mayo Foundation and the Intramural
Program, NIH project Z01HD00064204.
NR 35
TC 22
Z9 25
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0147-5185
EI 1532-0979
J9 AM J SURG PATHOL
JI Am. J. Surg. Pathol.
PD SEP
PY 2011
VL 35
IS 9
BP 1311
EP 1326
DI 10.1097/PAS.0b013e31821ec4ce
PG 16
WC Pathology; Surgery
SC Pathology; Surgery
GA 806TG
UT WOS:000293834400007
PM 21836496
ER
PT J
AU Lago, CU
Sung, HJ
Ma, WZ
Wang, PY
Hwang, PM
AF Lago, Cory U.
Sung, Ho Joong
Ma, Wenzhe
Wang, Ping-Yuan
Hwang, Paul M.
TI p53, Aerobic Metabolism, and Cancer
SO ANTIOXIDANTS & REDOX SIGNALING
LA English
DT Review
ID MITOCHONDRIAL TRANSCRIPTION FACTOR; TUMOR-SUPPRESSOR P53;
LI-FRAUMENI-SYNDROME; RAT SKELETAL-MUSCLE; PHYSICAL-ACTIVITY;
DNA-BINDING; ENERGY-METABOLISM; OXIDATIVE STRESS; CARDIORESPIRATORY
FITNESS; P53-INDUCIBLE REGULATOR
AB p53 regulates the cell cycle and deoxyribonucleic acid (DNA) repair pathways as part of its unequivocally important function to maintain genomic stability. Intriguingly, recent studies show that p53 can also transactivate genes involved in coordinating the two major pathways of energy generation to promote aerobic metabolism, but how this serves to maintain genomic stability is less clear. In an attempt to understand the biology, this review presents human epidemiologic data on the inverse relationship between aerobic capacity and cancer incidence that appears to be mirrored by the impact of p53 on aerobic capacity in mouse models. The review summarizes mechanisms by which p53 regulates mitochondrial respiration and proposes how this might contribute to maintaining genomic stability. Although disparate in nature, the data taken together suggest that the promotion of aerobic metabolism by p53 serves as an important tumor suppressor activity and may provide insights for cancer prevention strategies in the future. Antioxid. Redox Signal. 15, 1739-1748.
C1 [Lago, Cory U.; Sung, Ho Joong; Ma, Wenzhe; Wang, Ping-Yuan; Hwang, Paul M.] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA.
[Sung, Ho Joong] Eulji Univ, Coll Hlth Sci, Dept Biomed Lab Sci, Gyeonggi Do, South Korea.
RP Hwang, PM (reprint author), NHLBI, Ctr Mol Med, NIH, Bldg 10-CRC,Rm 5-5330, Bethesda, MD 20892 USA.
EM hwangp@mail.nih.gov
NR 123
TC 20
Z9 20
U1 0
U2 6
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1523-0864
J9 ANTIOXID REDOX SIGN
JI Antioxid. Redox Signal.
PD SEP
PY 2011
VL 15
IS 6
BP 1739
EP 1748
DI 10.1089/ars.2010.3650
PG 10
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 803JA
UT WOS:000293576400017
PM 20919942
ER
PT J
AU Motegi, S
Leitner, WW
Lu, M
Tada, Y
Sardy, M
Wu, CJ
Chavakis, T
Udey, MC
AF Motegi, Sei-ichiro
Leitner, Wolfgang W.
Lu, Michael
Tada, Yayoi
Sardy, Miklos
Wu, Chuanjin
Chavakis, Triantafyllos
Udey, Mark C.
TI Pericyte-Derived MFG-E8 Regulates Pathologic Angiogenesis
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE angiogenesis; MFG-E8; melanoma; oxygen-induced retinopathy; pericyte
ID EPIDERMAL-GROWTH FACTOR-8; DISCOIDIN-DOMAIN PROTEIN; APOPTOTIC CELLS;
RETINAL NEOVASCULARIZATION; INDUCED RETINOPATHY; ENDOTHELIAL-CELLS;
TUMOR VASCULATURE; DENDRITIC CELLS; 10T1/2 CELLS; MOUSE MODEL
AB Objective-MFG-E8 (also called lactadherin and SED1) is a secreted glycoprotein that has been previously implicated in enhancement of vascular endothelial growth factor-dependent angiogenesis. Major sources of MFG-E8 in vivo and precise mechanisms of MFG-E8 action remain undetermined. The objective of this study was to identify important sources of MFG-E8 in vivo and further elucidate the role(s) of MFG-E8 in the regulation of angiogenesis.
Methods and Results-We used knockout mice and anti-MFG-E8 antibodies to study MFG-E8 function in vivo. In melanomas and in retinas of mice with oxygen-induced retinopathy, MFG-E8 colocalized with pericytes rather than endothelial cells, and platelet-derived growth factor receptor beta+ pericytes/pericyte precursors purified from tumors contained large amounts of MFG-E8 mRNA. Tumor-and retinopathy-associated angiogenesis was diminished in MFG-E8 knockout mice, and pericyte coverage of neovessels was reduced. Inhibition of MFG-E8 production by 10T1/2 cells (surrogate pericyte/pericyte precursors) using small interfering RNAs and short hairpin RNAs, or inhibition of MFG-E8 action with some anti-MFG-E8 antibodies, selectively attenuated migration in vitro. Significantly, the anti-MFG-E8 antibodies that inhibited 10T1/2 cell migration in vitro also inhibited pathological angiogenesis in vivo.
Conclusion-These studies strongly implicate MFG-E8 in pericyte/pericyte precursor function and indicate that MFG-E8-directed therapeutics may merit further development. (Arterioscler Thromb Vasc Biol. 2011;31:2024-2034.)
C1 [Motegi, Sei-ichiro; Leitner, Wolfgang W.; Lu, Michael; Tada, Yayoi; Sardy, Miklos; Wu, Chuanjin; Udey, Mark C.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20802 USA.
[Chavakis, Triantafyllos] NCI, Expt Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20802 USA.
RP Udey, MC (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 10,Rm 12N238, Bethesda, MD 20802 USA.
EM udeym@mail.nih.gov
RI Leitner, Wolfgang/F-5741-2011
OI Leitner, Wolfgang/0000-0003-3125-5922
FU National Institutes of Health, Center for Cancer Research, National
Cancer Institute; Japan Foundation for Aging and Health; Japan Society
for Promotion of Science at the National Institutes of Health
FX This work was supported by the Intramural Program of the National
Institutes of Health, Center for Cancer Research, National Cancer
Institute (to M.C.U.). Dr Motegi was supported, in part, by project
grants from the Japan Foundation for Aging and Health and a Japan
Society for Promotion of Science Research Fellowship for Japanese
Biomedical and Behavioral Researchers at the National Institutes of
Health.
NR 55
TC 19
Z9 19
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD SEP
PY 2011
VL 31
IS 9
BP 2024
EP U281
DI 10.1161/ATVBAHA.111.232587
PG 33
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 808DF
UT WOS:000293955200021
PM 21737783
ER
PT J
AU Hiranita, T
Soto, PL
Tanda, G
Katz, JL
AF Hiranita, Takato
Soto, Paul L.
Tanda, Gianluigi
Katz, Jonathan L.
TI Lack of cocaine-like discriminative-stimulus effects of sigma-receptor
agonists in rats
SO BEHAVIOURAL PHARMACOLOGY
LA English
DT Article
DE sigma receptor; 1,3-di-o-tolylguanidine; cocaine;
discriminative-stimulus effects; dopamine-uptake inhibitor;
methylphenidate; PRE-084; WIN 35 428
ID CONDITIONED PLACE PREFERENCE; DOPAMINE; MICE; METHAMPHETAMINE; BLOCKADE;
LIGANDS; INVOLVEMENT; ACTIVATION; MORPHINE
AB Previous studies demonstrated the effectiveness of selective sigma-receptor (sigma R) agonists [1,3-di-o-tolylguanidine (DTG), PRE-084] as reinforcers in rats trained to self-administer cocaine. Similar to cocaine, these drugs increased nucleus accumbens shell dopamine levels, and effects of DTG, but not PRE-084, on dopamine seemed to be mediated by sigma Rs. In addition, sigma R antagonists blocked self-administration of sigma R agonists, but were inactive against reinforcing and neurochemical effects of cocaine. Thus, pharmacologically distinct mechanisms likely underlie the reinforcing and neurochemical effects of sigma R agonists and cocaine. This study further examined the cocaine-like effects of sigma R agonists in rats trained to discriminate injections of cocaine from saline to assess the similarity of their subjective effects. Standard dopamine-uptake inhibitors (WIN 35 428, methylphenidate), but neither sigma R agonist (PRE-084, DTG), produced full cocaine-like discriminative-stimulus effects. The lack of effects of sigma R agonists was obtained regardless of route of administration (intraperitoneal, subcutaneous, or intravenous) or pretreatment time (5 or 30 min before sessions). The present results demonstrate differences in the discriminative-stimulus effects of cocaine and selective sigma R agonists, indicating that an overlap of subjective effects is not necessary for sigma R agonist self-administration. The previously found differences in neurochemical effects of cocaine and sigma R agonists may contribute to their different subjective effects. Behavioural Pharmacology 22:525-530 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Hiranita, Takato; Tanda, Gianluigi; Katz, Jonathan L.] NIDA, Psychobiol Sect, Medicat Discovery Res Branch, Intramural Res Program,Dept Hlth & Human Serv,NIH, Baltimore, MD 21224 USA.
[Soto, Paul L.] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD USA.
RP Katz, JL (reprint author), NIDA, Psychobiol Sect, Medicat Discovery Res Branch, Intramural Res Program,Dept Hlth & Human Serv,NIH, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM jkatz@intra.nida.nih.gov
RI Tanda, Gianluigi/B-3318-2009; Hiranita, Takato/G-6567-2011
OI Tanda, Gianluigi/0000-0001-9526-9878;
FU National Institute on Drug Abuse
FX The authors thank Patty Ballerstadt for administrative assistance and
Bettye Campbell for technical assistance. This study was supported by
the Intramural Research Program of the National Institute on Drug Abuse.
The animal housing facilities are fully accredited by the Association
for Assessment and Accreditation of Laboratory Animal Care International
and all procedures were conducted in accordance with the guidelines of
the Institutional Care and Use Committee of the NIDA Intramural Research
Program and the 1996 National Research Council and Guide for Care and
Use of Laboratory Animals.
NR 30
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U1 0
U2 4
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 2011
VL 22
IS 5-6
BP 525
EP 530
DI 10.1097/FBP.0b013e328349ab22
PG 6
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA 806QM
UT WOS:000293825000017
PM 21808192
ER
PT J
AU Yum, S
Choi, J
Hong, S
Park, MH
Lee, J
Ha, NC
Jung, Y
AF Yum, Soohwan
Choi, Jeongyoun
Hong, Sungchae
Park, Myung Hee
Lee, Jaewon
Ha, Nam-Chul
Jung, Yunjin
TI Hyperoxia attenuates the inhibitory effect of nitric oxide donors on HIF
prolyl-4-hydroxylase-2: Implication on discriminative effect of nitric
oxide on HIF prolyl-4-hydroxylase-2 and collagen prolyl-4-hydroxylase
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE Nitric oxide; Hyperoxia; HIF polyl-4-hydroxylase; Collagen
prolyl-4-hydroxylase; Hypoxia inducible factor
ID HYPOXIA-INDUCIBLE FACTOR; PROLYL 4-HYDROXYLASES; KEY ENZYMES;
HYDROXYLATION; ALPHA; FIBROBLASTS; HIF-1-ALPHA; ACTIVATION; STABILITY;
PATHWAY
AB Prolyl 4-hydroxylases (P4Hs), such as collagen prolyl-4-hydroxylases (CPHs) and hypoxia inducible factor prolyl-4-hydroxylases (HPHs), have recently been recognized as promising drug targets for the treatment of fibrotic and ischemic diseases. CPHs and HPHs catalyze identical metabolic reactions, yet lead to quite different physiological consequences, collagen synthesis and the regulation of oxygen homeostasis. Selective modulation of the two enzymes should provide a therapeutic benefit upon pharmacotherapy. In an in vitro VHL capture assay, hydroxylation of the 19mer HIF peptide (corresponding to HIF-1 alpha residues 556-574) by HPH-2 was effectively prevented by nitric oxide (NO) donors, (+/-)-S-nitroso-N-acetylpenicillamine (SNAP) and S-nitrosoglutathione. The NO donors also caused inhibition of HPHs and accumulation of nonhydroxylated HIF-1 alpha protein in A549 human lung adenocarcinoma cells. Hyperoxia (100% O(2)) attenuated both NO donor-induced accumulation of HIF-1 alpha and inhibition of HPH-mediated hydroxylation. In the presence of a proteasome inhibitor, MG132, the hyperoxia-mediated degradation of HIF-1 alpha was deterred and hydroxylated HIF-1 alpha was detected. SNAP, while being an effective inhibitor of proline 4-hydroxylation of HIF-1 alpha by HPH-2, did not diminish praline hydroxylation of collagen by CPHs. Our data suggest that NO inhibits HPH-2 via competing with dioxygen and that the discriminative effect of NO on CPHs and HPH-2 is attributable to the difference in the affinity of the two enzymes toward dioxygen. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Yum, Soohwan; Choi, Jeongyoun; Hong, Sungchae; Park, Myung Hee; Lee, Jaewon; Ha, Nam-Chul; Jung, Yunjin] Pusan Natl Univ, Coll Pharm, Pusan 609735, South Korea.
[Park, Myung Hee] NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
RP Jung, Y (reprint author), Pusan Natl Univ, Coll Pharm, Pusan 609735, South Korea.
EM jungy@pusan.ac.kr
RI Lee, Jaewon/N-9064-2013
FU Ministry of Education, Science and Technology [2009-0071594]; Ministry
for Health, Welfare and Family Affairs, Republic of Korea [A080640]
FX This research was supported by Basic Science Research Program through
the National Research Foundation of Korea (NRF) funded by the Ministry
of Education, Science and Technology (No: 2009-0071594) and a grant of
the Korea Healthcare technology R and D Project (A080640), Ministry for
Health, Welfare and Family Affairs, Republic of Korea.
NR 23
TC 0
Z9 0
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0006-2952
J9 BIOCHEM PHARMACOL
JI Biochem. Pharmacol.
PD SEP 1
PY 2011
VL 82
IS 5
BP 485
EP 490
DI 10.1016/j.bcp.2011.05.033
PG 6
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 806PR
UT WOS:000293820600007
PM 21723853
ER
PT J
AU Giano, MC
Pochan, DJ
Schneider, JP
AF Giano, Michael C.
Pochan, Darrin J.
Schneider, Joel P.
TI Controlled biodegradation of Self-assembling beta-hairpin Peptide
hydrogels by proteolysis with matrix metalloproteinase-13
SO BIOMATERIALS
LA English
DT Article
DE Biodegradation; Matrix metalloproteinase; Peptide; Self assembly;
Hydrogel; Extracellular matrix
ID ENGINEERED PEG HYDROGELS; BIOMEDICAL APPLICATIONS;
SUBSTRATE-SPECIFICITY; SCAFFOLD DESIGN; CELL-MIGRATION; NETWORKS;
BIOMATERIALS; DEGRADATION; TISSUE; CARTILAGE
AB Controlled biodegradation specific to matrix metalloproteinase-13 was incorporated into the design of self-assembling beta-hairpin peptide hydrogels. Degrading Peptides (DP peptides) are a series of five peptides that have varying proteolytic susceptibilities toward MMP-13. These peptides undergo environmentally triggered folding and self-assembly under physiologically relevant conditions (150 mm NaCl. pH 7.6) to form self-supporting hydrogels. In the presence of enzyme, gels prepared from distinct peptides are degraded at rates that differ according to the primary sequence of the single peptide comprising the gel. Material degradation was monitored by oscillatory shear rheology over the course of 14 days, where overall degradation of the gels vary from 5% to 70%. Degradation products were analyzed by HPLC and identified by electrospray-ionization mass spectrometry. This data shows that proteolysis of the parent peptides constituting each gel occurs at the intended sequence location. DP hydrogels show specificity to MMP-13 and are only minimally cleaved by matrix metalloproteinase-3 (MMP-3), another common enzyme present during tissue injury. In vitro migration assays performed with SW1353 cells show that migration rates through each gel differs according to peptide sequence, which is consistent with the proteolysis studies using exogenous MMP-13. Published by Elsevier Ltd.
C1 [Giano, Michael C.; Schneider, Joel P.] NCI, Canc Res Ctr, Frederick, MD 21701 USA.
[Giano, Michael C.] Univ Delaware, Dept Chem & Biochem, Newark, DE 19716 USA.
[Pochan, Darrin J.] Univ Delaware, Dept Mat Sci & Engn, Newark, DE 19716 USA.
RP Schneider, JP (reprint author), NCI, Canc Res Ctr, Frederick, MD 21701 USA.
EM Joel.Schneider@nih.gov
RI Schneider, Joel/N-2610-2014
FU National Cancer Institute of the National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Cancer Institute of the National Institutes of Health. I would
personally like to thank Daphne A. Salick and Monica C. Branco for
intellectual conversations.
NR 60
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Z9 42
U1 3
U2 79
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0142-9612
J9 BIOMATERIALS
JI Biomaterials
PD SEP
PY 2011
VL 32
IS 27
BP 6471
EP 6477
DI 10.1016/j.biomaterials.2011.05.052
PG 7
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA 801HR
UT WOS:000293429700012
PM 21683437
ER
PT J
AU Domire, JS
Green, JA
Lee, KG
Johnson, AD
Askwith, CC
Mykytyn, K
AF Domire, Jacqueline S.
Green, Jill A.
Lee, Kirsten G.
Johnson, Andrew D.
Askwith, Candice C.
Mykytyn, Kirk
TI Dopamine receptor 1 localizes to neuronal cilia in a dynamic process
that requires the Bardet-Biedl syndrome proteins
SO CELLULAR AND MOLECULAR LIFE SCIENCES
LA English
DT Article
DE Ciliopathy; Neuronal cilia; Dopamine receptor 1; Bardet-Biedl syndrome
ID INTRAFLAGELLAR TRANSPORT; COUPLED-RECEPTORS; PLASMA-MEMBRANE; RHODOPSIN;
COMPLEX; MICE; ACTIVATION; FLAGELLA; AMYGDALA; BRAIN
AB Primary cilia are nearly ubiquitous cellular appendages that provide important sensory and signaling functions. Ciliary dysfunction underlies numerous human diseases, collectively termed ciliopathies. Primary cilia have distinct functions on different cell types and these functions are defined by the signaling proteins that localize to the ciliary membrane. Neurons throughout the mammalian brain possess primary cilia upon which certain G protein-coupled receptors localize. Yet, the precise signaling proteins present on the vast majority of neuronal cilia are unknown. Here, we report that dopamine receptor 1 (D1) localizes to cilia on mouse central neurons, thereby implicating neuronal cilia in dopamine signaling. Interestingly, ciliary localization of D1 is dynamic, and the receptor rapidly translocates to and from cilia in response to environmental cues. Notably, the translocation of D1 from cilia requires proteins mutated in the ciliopathy Bardet-Biedl syndrome (BBS), and we find that one of the BBS proteins, Bbs5, specifically interacts with D1.
C1 [Domire, Jacqueline S.; Green, Jill A.; Mykytyn, Kirk] Ohio State Univ, Coll Med, Dept Pharmacol, Columbus, OH 43210 USA.
[Lee, Kirsten G.; Askwith, Candice C.] Ohio State Univ, Coll Med, Dept Neurosci, Columbus, OH 43210 USA.
[Johnson, Andrew D.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Ctr Populat Studies, Framingham, MA 01702 USA.
RP Mykytyn, K (reprint author), Ohio State Univ, Coll Med, Dept Pharmacol, 5034 Graves Hall,333 W 10th Ave, Columbus, OH 43210 USA.
EM mykytyn.1@osu.edu
RI Johnson, Andrew/G-6520-2013; Mykytyn, Kirk/E-3723-2011
OI Mykytyn, Kirk/0000-0002-0158-4592
FU NIH/National Institute of General Medical Sciences [T32 GM068412, R01
GM083120]
FX We are grateful to Joshua Stowell for technical assistance and David
Sibley (NINDS) for providing D1 WT and KO brains. This work was
supported in part by the Systems and Integrative Biology Training Grant
T32 GM068412(J.G.) and R01 GM083120 from the NIH/National Institute of
General Medical Sciences (K.M.).
NR 42
TC 55
Z9 56
U1 1
U2 9
PU SPRINGER BASEL AG
PI BASEL
PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND
SN 1420-682X
J9 CELL MOL LIFE SCI
JI Cell. Mol. Life Sci.
PD SEP
PY 2011
VL 68
IS 17
BP 2951
EP 2960
DI 10.1007/s00018-010-0603-4
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 808DS
UT WOS:000293957400010
PM 21152952
ER
PT J
AU Tomasi, D
Volkow, ND
AF Tomasi, Dardo
Volkow, Nora D.
TI Association between Functional Connectivity Hubs and Brain Networks
SO CEREBRAL CORTEX
LA English
DT Article
DE functional connectivity; 1000 functional connectomes
ID RESTING-STATE NETWORKS; VISUAL-ATTENTION TASKS; DEFAULT NETWORK;
ALZHEIMERS-DISEASE; WORKING-MEMORY; SMALL-WORLD; ACTIVATION PATTERNS;
MOTOR CORTEX; IMAGES; MRI
AB Functional networks are usually accessed with "resting-state" functional magnetic resonance imaging using preselected "seeds" regions. Frequently, however, the selection of the seed locations is arbitrary. Recently, we proposed local functional connectivity density mapping (FCDM), an ultrafast data-driven to locate highly connected brain regions (functional hubs). Here, we used the functional hubs obtained from local FCDM to determine the functional networks of the resting state in 979 healthy subjects without a priori hypotheses on seed locations. In addition, we computed the global functional connectivity hubs. Seven networks covering 80% of the gray matter volume were identified. Four major cortical hubs (ventral precuneus/posterior cingulate, inferior parietal cortex, cuneus, and postcentral gyrus) were linked to 4 cortical networks (default mode, dorsal attention, visual, and somatosensory). Three subcortical networks were associated to the major subcortical hubs (cerebellum, thalamus, and amygdala). The networks differed in their resting activity and topology. The higher coupling and overlap of subcortical networks was associated to higher contribution of short-range functional connectivity in thalamus and cerebellum. Whereas cortical local FCD hubs were also hubs of long-range connectivity, which corroborates the key role of cortical hubs in network architecture, subcortical hubs had minimal long-range connectivity. The significant variability among functional networks may underlie their sensitivity/resilience to neuropathology.
C1 [Tomasi, Dardo; Volkow, Nora D.] NIAAA, Bethesda, MD 20892 USA.
[Volkow, Nora D.] NIDA, Bethesda, MD 20892 USA.
RP Tomasi, D (reprint author), Brookhaven Natl Lab, Lab Neuroimaging LNI NIAAA, Dept Med, Bldg 490,30 Bell Ave, Upton, NY 11973 USA.
EM tomasi@bnl.gov
RI Tomasi, Dardo/J-2127-2015
FU National Institutes of Alcohol Abuse and Alcoholism [2RO1AA09481]
FX National Institutes of Alcohol Abuse and Alcoholism (2RO1AA09481).
NR 63
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U1 3
U2 19
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
J9 CEREB CORTEX
JI Cereb. Cortex
PD SEP
PY 2011
VL 21
IS 9
BP 2003
EP 2013
DI 10.1093/cercor/bhq268
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 807PH
UT WOS:000293911700005
PM 21282318
ER
PT J
AU Markowitz, JT
Laffel, LMB
Volkening, LK
Anderson, BJ
Nansel, TR
Weissberg-Benchell, J
Wysocki, T
AF Markowitz, J. T.
Laffel, L. M. B.
Volkening, L. K.
Anderson, B. J.
Nansel, T. R.
Weissberg-Benchell, J.
Wysocki, T.
TI Validation of an abbreviated adherence measure for young people with
Type 1 diabetes
SO DIABETIC MEDICINE
LA English
DT Article
DE adherence; paediatrics; Type 1 diabetes
ID STRUCTURED INTERVIEW; SELF-MANAGEMENT; INTERVENTION; RELIABILITY;
VALIDITY; SCALE
AB Aims Adherence to diabetes-related tasks is an important construct. The Diabetes Self-Management Profile is a validated, semi-structured interview assessing adherence in paediatric patients with Type 1 diabetes. We created and validated a brief questionnaire version of the Diabetes Self-Management Profile called the Diabetes Self-Management Questionnaire.
Methods Young people with Type 1 diabetes, ages 9-15 years (n = 338) and their parents provided data from chart review, interview and questionnaires.
Results Diabetes Self-Management Questionnaire scores correlated significantly with Diabetes Self-Management Profile scores, HbA(1c), blood glucose monitoring frequency and other measures associated with adherence and/or glycaemic control (P <= 0.01 for all). Young people and parent scores were correlated (r = 0.55, P < 0.0001). The Diabetes Self-Management Questionnaire demonstrated modest internal consistency (Cronbach's alpha = 0.59), adequate for a brief measure of multidimensional adherence. In addition, factor analysis confirmed one factor.
Conclusions This brief adherence questionnaire demonstrated construct validity in young people 9-15 years old and their parents and may have utility in clinical and research settings.
C1 [Laffel, L. M. B.] Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA.
[Anderson, B. J.] Baylor Coll Med, Houston, TX 77030 USA.
[Nansel, T. R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Weissberg-Benchell, J.] Childrens Mem Hosp, Chicago, IL 60614 USA.
[Wysocki, T.] Nemours Childrens Clin, Jacksonville, FL USA.
RP Laffel, LMB (reprint author), Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, 1 Joslin Pl, Boston, MA 02215 USA.
EM lori.laffel@joslin.harvard.edu
OI Nansel, Tonja/0000-0002-8298-7595
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD); NIH [T32 DK007260]; National Institute of Diabetes
and Digestive and Kidney Diseases [DK-46887]; Charles H. Hood
Foundation; Maria Griffin Drury Pediatric Fund; Katherine Adler Astrove
Youth Education Fund; [N01-HD-4-3363]; [N01-HD-4-3362];
[N01-HD-4-3361]; [N01-HD-4-3364]; [N01-HD-3-3360]
FX This research was supported in part by the intramural research program
of the Eunice Kennedy Shriver National Institute of Child Health and
Human Development (NICHD). The following investigators and institutions
made up the steering committee of the Family Management of Childhood
Diabetes multi-site trial: Jill Weissberg-Benchell PhD, Grayson Holmbeck
PhD (Children's Memorial Hospital, Chicago, Contract N01-HD-4-3363);
Barbara Anderson PhD (Texas Children's Hospital, Houston, Contract
N01-HD-4-3362); Tim Wysocki PhD, Amanda Lochrie PhD (Nemours Children's
Clinic, Jacksonville, FL, Contract N01-HD-4-3361); Lori Laffel MD MPH,
Deborah Butler MSW, Lisa Volkening MA (Joslin Diabetes Center, Boston,
Contract N01-HD-4-3364); Tonja Nansel PhD, Ronald Iannotti PhD (NICHD,
Bethesda, MD); Cheryl McDonnell PhD, MaryAnn D'Elio (James Bell
Associates, Arlington, VA, Contract N01-HD-3-3360). This work was also
supported in part by NIH Training Grant No. T32 DK007260, a grant from
the National Institute of Diabetes and Digestive and Kidney Diseases
(DK-46887), the Charles H. Hood Foundation, the Maria Griffin Drury
Pediatric Fund and the Katherine Adler Astrove Youth Education Fund.
NR 12
TC 10
Z9 10
U1 2
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0742-3071
J9 DIABETIC MED
JI Diabetic Med.
PD SEP
PY 2011
VL 28
IS 9
BP 1113
EP 1117
DI 10.1111/j.1464-5491.2011.03321.x
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 807NG
UT WOS:000293905000018
PM 21843307
ER
PT J
AU Cheng, YF
Martinez-Guerrero, LJ
Wright, SH
Kuester, RK
Hooth, MJ
Sipes, IG
AF Cheng, Yaofeng
Martinez-Guerrero, Lucy J.
Wright, Stephen H.
Kuester, Robert K.
Hooth, Michelle J.
Sipes, I. Glenn
TI Characterization of the Inhibitory Effects of N-Butylpyridinium Chloride
and Structurally Related Ionic Liquids on Organic Cation Transporters
1/2 and Human Toxic Extrusion Transporters 1/2-K In Vitro and In Vivo
SO DRUG METABOLISM AND DISPOSITION
LA English
DT Article
ID FEMALE B6C3F1 MICE; MALE F344 RATS; TETRAALKYLAMMONIUM COMPOUNDS;
PROXIMAL TUBULES; RENAL SECRETION; METFORMIN; PHARMACOKINETICS;
MULTIDRUG; KIDNEY; MATE1
AB Ionic liquids (ILs) are a class of salts that are expected to be used as a new source of solvents and for many other applications. Our previous studies revealed that selected ILs, structurally related organic cations, are eliminated exclusively in urine as the parent compound, partially mediated by renal transporters. This study investigated the inhibitory effects of N-butylpyridinium chloride (NBuPy-Cl) and structurally related ILs on organic cation transporters (OCTs) and multidrug and toxic extrusion transporters (MATEs) in vitro and in vivo. After Chinese hamster ovary cells expressing rat (r) OCT1, rOCT2, human (h) OCT2, hMATE1, or hMATE2-K were constructed, the ability of NBuPy-Cl, 1-methyl-3-butylimidazolium chloride (Bmim-Cl), N-butyl-N-methylpyrrolidinium chloride (BmPy-Cl), and alkyl substituted pyridinium ILs to inhibit these transporters was determined in vitro. NBuPy-Cl (0, 0.5, or 2 mg/kg per hour) was also infused into rats to assess its effect on the pharmacokinetics of metformin, a substrate of OCTs and MATEs. NBuPy-Cl, Bmim-Cl, and BmPy-Cl displayed strong inhibitory effects on these transporters (IC50 = 0.2-8.5 mu M). In addition, the inhibitory effects of alkyl-substituted pyridinium ILs on OCTs increased dramatically as the length of the alkyl chain increased. The IC50 values were 0.1, 3.8, 14, and 671 mu M (hexyl-, butyl-, and ethyl-pyridinium and pyridinium chloride) for rOCT2-mediated metformin transport. Similar structurally related inhibitory kinetics were also observed for rOCT1 and hOCT2. The in vivo coadministration study revealed that NBuPy-Cl reduced the renal clearance of metformin in rats. These results demonstrate that ILs compete with other substrates of OCTs and MATEs and could alter the in vivo pharmacokinetics of such substrates.
C1 [Cheng, Yaofeng; Kuester, Robert K.; Sipes, I. Glenn] Univ Arizona, Dept Pharmacol, Coll Med, Tucson, AZ 85724 USA.
[Martinez-Guerrero, Lucy J.; Wright, Stephen H.] Univ Arizona, Dept Physiol, Coll Med, Tucson, AZ 85724 USA.
[Hooth, Michelle J.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
RP Sipes, IG (reprint author), Univ Arizona, Dept Pharmacol, Coll Med, POB 245050, Tucson, AZ 85724 USA.
EM sipes@email.arizona.edu
FU National Institutes of Health National Institute of Environmental Health
Sciences [N01-ES45529, ES06694]; National Institutes of Health National
Institute of Diabetes and Digestive and Kidney Diseases [DK58251]
FX This work was supported by the National Institutes of Health National
Institute of Environmental Health Sciences [Contract N01-ES45529]
(National Toxicology Program); the National Institutes of Health
National Institute of Diabetes and Digestive and Kidney Diseases [Grant
DK58251]; and the National Institutes of Health National Institute of
Environmental Health Sciences [Grant ES06694].
NR 42
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U1 0
U2 14
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0090-9556
J9 DRUG METAB DISPOS
JI Drug Metab. Dispos.
PD SEP
PY 2011
VL 39
IS 9
BP 1755
EP 1761
DI 10.1124/dmd.110.035865
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 809JV
UT WOS:000294050900033
PM 21646436
ER
PT J
AU Schirren, J
Donges, T
Melzer, M
Schonmayr, R
Eberlein, M
Bolukbas, S
Walsh, G
Weder, W
Turna, A
Cassivi, S
Athanassiadi, K
AF Schirren, Joachim
Doenges, Tina
Melzer, Michael
Schoenmayr, Robert
Eberlein, Michael
Boeluekbas, Servet
Walsh, G.
Weder, W.
Turna, A.
Cassivi, S.
Athanassiadi, K.
TI En bloc resection of non-small-cell lung cancer invading the spine
SO EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY
LA English
DT Article; Proceedings Paper
CT 18th European Conference on General Thoracic Surgery of the
European-Society-of-Thoracic-Surgeons
CY MAY 30-JUN 02, 2010
CL Valladolid, SPAIN
SP European Soc Thorac Surg
DE Spine; NSCLC; Surgery; Multimodality Treatment; Vertebrectomy
ID SUPERIOR SULCUS TUMORS; SURGICAL RESECTION; INDUCTION CHEMORADIATION;
THORACIC INLET; MANAGEMENT; INVOLVEMENT; STAGE; THERAPY; TRENDS
AB Objective: To describe our surgical en bloc approach and to assess the outcome and survival of non-small-cell lung cancer (NSCLC) invading the spine. Methods: We retrospectively reviewed our prospective database of all patients, who underwent lung resection with en bloc hemivertebrectomy or total vertebrectomy for NSCLC between January 2003 and December 2008 in an individualized multimodality treatment concept. Survival was estimated by the Kaplan-Meier method. Log-rank analyses were used to compare groups. Results: Twenty-eight patients (age 58.9 +/- 12.9 years) were diagnosed with NSCLC invading the spine at a single center. Eight of those patients were inoperable. Twenty patients proceeded to surgery with en bloc hemivertebrectomy (n = 16) or total vertebrectomy (n = 4). Six patients had induction chemotherapy (30%). Complete resection could be achieved in 16 patients (80%). Morbidity was observed in eight patients (40%); no mortality occurred. Adjuvant radiation (n = 14) or chemoradiation (n = 6) was administered with 66 Gy. The mean survival and 5-year survival for patients, who underwent surgery (n = 20), were 46.0 months and 47%, respectively. Inoperable patients had poorer survival (14.0 months; p = 0.004). Sublobar resections (p = 0.002) and incomplete resections (p = 0.02) were associated with inferior survival. Adjuvant chemoradiation (p = 0.088), hemivertebrectomy (p = 0.062), and age < 70 years (p = 0.076) trended toward prolonged survival. Conclusions: Multimodality treatment including en bloc lung resections with hemivertebrectomy or total vertebrectomy offer promising long-term survival in highly selected patients with NSCLC invading the spine. These extended resections can be performed with acceptable morbidity and mortality in specialized centers. Patients aged >= 70 years should be selected very carefully for radical resection. Sublobar resections should be avoided. (C) 2011 European Association for Cardio-Thoracic Surgery. Published by Elsevier B. V. All rights reserved.
C1 [Schirren, Joachim; Doenges, Tina; Boeluekbas, Servet] Dr Horst Schmidt Klin, Dept Thorac Surg, D-65199 Wiesbaden, Germany.
[Melzer, Michael; Schoenmayr, Robert] Dr Horst Schmidt Klin, Dept Neurosurg, D-65199 Wiesbaden, Germany.
[Eberlein, Michael] Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, Baltimore, MD USA.
[Eberlein, Michael] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
RP Bolukbas, S (reprint author), Dr Horst Schmidt Klin, Dept Thorac Surg, Ludwig Erhard Str 100, D-65199 Wiesbaden, Germany.
EM Dr.Bolukbas@gmx.de
NR 23
TC 9
Z9 9
U1 1
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1010-7940
J9 EUR J CARDIO-THORAC
JI Eur. J. Cardio-Thorac. Surg.
PD SEP
PY 2011
VL 40
IS 3
BP 647
EP 654
DI 10.1016/j.ejcts.2010.12.046
PG 8
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 806QF
UT WOS:000293824000031
PM 21334220
ER
PT J
AU Janssens, ACJW
Ioannidis, JPA
Bedrosian, S
Boffetta, P
Dolan, SM
Dowling, N
Fortier, I
Freedman, AN
Grimshaw, JM
Gulcher, J
Gwinn, M
Hlatky, MA
Janes, H
Kraft, P
Melillo, S
O'Donnell, CJ
Pencina, MJ
Ransohoff, D
Schully, SD
Seminara, D
Winn, DM
Wright, CF
van Duijn, CM
Little, J
Khoury, MJ
AF Janssens, A. Cecile J. W.
Ioannidis, John P. A.
Bedrosian, Sara
Boffetta, Paolo
Dolan, Siobhan M.
Dowling, Nicole
Fortier, Isabel
Freedman, Andrew N.
Grimshaw, Jeremy M.
Gulcher, Jeffrey
Gwinn, Marta
Hlatky, Mark A.
Janes, Holly
Kraft, Peter
Melillo, Stephanie
O'Donnell, Christopher J.
Pencina, Michael J.
Ransohoff, David
Schully, Sheri D.
Seminara, Daniela
Winn, Deborah M.
Wright, Caroline F.
van Duijn, Cornelia M.
Little, Julian
Khoury, Muin J.
TI Strengthening the reporting of genetic risk prediction studies (GRIPS):
explanation and elaboration
SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; HEART-DISEASE RISK; OPERATING CHARACTERISTIC
CURVE; TYPE-2 DIABETES RISK; COMMON DISEASES; RECLASSIFICATION MEASURES;
MACULAR DEGENERATION; DIAGNOSTIC-ACCURACY; CARDIOVASCULAR RISK;
RANDOMIZED-TRIALS
AB The rapid and continuing progress in gene discovery for complex diseases is fuelling interest in the potential application of genetic risk models for clinical and public health practice.
The number of studies assessing the predictive ability is steadily increasing, but they vary widely in completeness of reporting and apparent quality.
Transparent reporting of the strengths and weaknesses of these studies is important to facilitate the accumulation of evidence on genetic risk prediction.
A multidisciplinary workshop sponsored by the Human Genome Epidemiology Network developed a checklist of 25 items recommended for strengthening the reporting of Genetic RIsk Prediction Studies (GRIPS), building on the principles established by prior reporting guidelines.
These recommendations aim to enhance the transparency, quality and completeness of study reporting and thereby to improve the synthesis and application of information from multiple studies that might differ in design, conduct or analysis.
C1 [Janssens, A. Cecile J. W.; van Duijn, Cornelia M.] Erasmus Univ, Med Ctr, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands.
[Ioannidis, John P. A.] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece.
[Ioannidis, John P. A.] Fdn Res & Technol, Biomed Res Inst, Ioannina, Greece.
[Ioannidis, John P. A.] Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA.
[Ioannidis, John P. A.] Tufts Med Ctr, Ctr Genet Epidemiol & Modeling, Boston, MA USA.
[Ioannidis, John P. A.] Tufts Med Ctr, Tufts CTSI, Inst Clin Res & Hlth Policy Studies, Boston, MA USA.
[Ioannidis, John P. A.] Stanford Univ, Sch Med, Stanford Prevent Res Ctr, Stanford, CA USA.
[Bedrosian, Sara; Dowling, Nicole; Gwinn, Marta; Melillo, Stephanie; Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA.
[Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA.
[Boffetta, Paolo] Int Prevent Res Inst, Lyon, France.
[Dolan, Siobhan M.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Obstet & Gynecol & Womens Hlth, Bronx, NY 10467 USA.
[Fortier, Isabel] Publ Populat Project Genom P3G, Montreal, PQ, Canada.
[Freedman, Andrew N.; Kraft, Peter; Schully, Sheri D.; Seminara, Daniela; Winn, Deborah M.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
[Grimshaw, Jeremy M.] Ottawa Hosp, Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada.
[Grimshaw, Jeremy M.] Univ Ottawa, Dept Med, Ottawa, ON, Canada.
[Gulcher, Jeffrey] DeCODE Genet, Reykjavik, Iceland.
[Hlatky, Mark A.] Stanford Univ, Dept Hlth Res & Policy, Palo Alto, CA 94304 USA.
[Janes, Holly] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Inst, Seattle, WA 98104 USA.
[Janes, Holly] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Div Cardiol, Sch Med, Boston, MA USA.
[Pencina, Michael J.] Boston Univ, Dept Biostat, Harvard Clin Res Inst, Boston, MA 02215 USA.
[Ransohoff, David] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
[Wright, Caroline F.] PHG Fdn, Cambridge, England.
[Little, Julian] Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON, Canada.
RP Janssens, ACJW (reprint author), Erasmus Univ, Med Ctr, Dept Epidemiol, POB 2040, NL-3000 CA Rotterdam, Netherlands.
EM a.janssens@erasmusmc.nl
RI Ioannidis, John/G-9836-2011; Grimshaw, Jeremy/D-8726-2013; janssens,
cecile/L-1075-2015; Wright, Caroline/N-5355-2015;
OI Janssens, A Cecile/0000-0002-6153-4976; Wright,
Caroline/0000-0003-2958-5076; Grimshaw, Jeremy/0000-0001-8015-8243
FU National Heart, Lung, and Blood Institute; National Cancer Institute,
National Institutes of Health; Donald W. Reynolds Foundation; Leducq
Foundation
FX This study was supported by grants from the National Heart, Lung, and
Blood Institute and National Cancer Institute, National Institutes of
Health; the Donald W. Reynolds Foundation; and the Leducq Foundation.
Additional support for DNA extraction, reagents, and data analysis was
provided by Roche Diagnostics and Amgen. Genotyping of the 9p21.3
variant was performed by Celera. The funding sources had no role in the
design, conduct, or reporting of this study or the decision to submit
the manuscript for publication' [53].
NR 92
TC 16
Z9 17
U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0014-2972
J9 EUR J CLIN INVEST
JI Eur. J. Clin. Invest.
PD SEP
PY 2011
VL 41
IS 9
BP 1010
EP 1035
DI 10.1111/j.1365-2362.2011.02493.x
PG 26
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 802KJ
UT WOS:000293509200013
PM 21434890
ER
PT J
AU Sanu, O
Lamont, RF
AF Sanu, Olaleye
Lamont, Ronald F.
TI Hyperemesis gravidarum: pathogenesis and the use of antiemetic agents
reply
SO EXPERT OPINION ON PHARMACOTHERAPY
LA English
DT Letter
C1 [Sanu, Olaleye] Hillingdon Hosp NHS Fdn Trust, Dept Obstet & Gynaecol, Uxbridge, Middx, England.
[Lamont, Ronald F.] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI 48201 USA.
RP Sanu, O (reprint author), Hillingdon Hosp NHS Fdn Trust, Dept Obstet & Gynaecol, Pield Heath Rd, Uxbridge, Middx, England.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1465-6566
J9 EXPERT OPIN PHARMACO
JI Expert Opin. Pharmacother.
PD SEP
PY 2011
VL 12
IS 13
BP 2140
EP 2140
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 803RZ
UT WOS:000293599700015
ER
PT J
AU Huang, SYN
Pommier, Y
Marchand, C
AF Huang, Shar-yin N.
Pommier, Yves
Marchand, Christophe
TI Tyrosyl-DNA Phosphodiesterase 1 (Tdp1) inhibitors
SO EXPERT OPINION ON THERAPEUTIC PATENTS
LA English
DT Editorial Material
DE bleomycin; DNA repair; furamidine; topoisomerase
ID TOPOISOMERASE-I INHIBITORS; STRAND BREAK REPAIR; CELL LUNG-CANCER;
SPINOCEREBELLAR ATAXIA; COVALENT COMPLEXES; AXONAL NEUROPATHY; DAMAGE;
PATHWAYS; IDENTIFICATION; CAMPTOTHECIN
AB Inhibitors of topoisomerase I (Top1) that result in stalled Top1 cleavage complexes (Top1cc) are commonly employed against cancer. Combination chemotherapy with DNA repair inhibitors can potentially improve response to these widely used chemotherapeutics. One line of inquiry focuses on inhibitors of tyrosyl-DNA phosphodiesterase 1 (Tdp1), a repair enzyme for Top1cc. Tdp1 catalyzes the hydrolysis of DNA adducts covalently linked to the 3'-phosphate of DNA, including Top1-derived peptides and also 3'-phosphoglycolates. Tdp1 inhibitors should synergize not only with Top1-targeting drugs (camptothecins, indenoisoquinolines), but also with bleomycin, topoisomerase II (Top2) inhibitors (etoposide, doxorubicin) and DNA alkylating agents. Here, we summarize the structure-activity relationship obtained from the reported Tdp1 inhibitors. Better understanding of Top1cc repair in vivo coupled with detailed structural studies on Tdp1-inhibitor interaction will be crucial in guiding the rational design of Tdp1 inhibitors.
C1 [Huang, Shar-yin N.; Pommier, Yves; Marchand, Christophe] NCI, Ctr Canc Res, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA.
RP Pommier, Y (reprint author), NCI, Ctr Canc Res, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA.
EM Pommier@nih.gov
FU Intramural NIH HHS [Z01 BC006150-26]
NR 47
TC 26
Z9 26
U1 1
U2 6
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1354-3776
J9 EXPERT OPIN THER PAT
JI Expert Opin. Ther. Patents
PD SEP
PY 2011
VL 21
IS 9
BP 1285
EP 1292
DI 10.1517/13543776.2011.604314
PG 8
WC Chemistry, Medicinal; Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 807SK
UT WOS:000293919800001
PM 21843105
ER
PT J
AU Grace, MB
Cliffer, KD
Moyer, BR
Coleman, CN
Prasher, JM
Hatchett, R
Mercier, J
Manning, RG
Bader, JL
Disbrow, GL
Kovacs, GR
AF Grace, Marcy B.
Cliffer, Kenneth D.
Moyer, Brian R.
Coleman, C. Norman
Prasher, Joanna M.
Hatchett, Richard
Mercier, John
Manning, Ronald G.
Bader, Judith L.
Disbrow, Gary L.
Kovacs, Gerald R.
TI THE US GOVERNMENT'S MEDICAL COUNTERMEASURE PORTFOLIO MANAGEMENT FOR
NUCLEAR AND RADIOLOGICAL EMERGENCIES: SYNERGY FROM INTERAGENCY
COOPERATION
SO HEALTH PHYSICS
LA English
DT Article
AB Following the attacks of 11 September 2001, emergency preparedness within the U. S. Department of Health and Human Services, as well as at the Department of Defense and other federal agencies, received higher visibility, new mandates and increased funding. Emergency deployment teams increased the frequency of drills to enable better response to the health consequences of mass-casualty incidents. Interagency coordination has also continued to increase to more efficiently and effectively leverage federal resources toward emergency medical preparedness for both civilian and military populations. Health Phys. 101(3):238-247; 2011
C1 [Grace, Marcy B.; Manning, Ronald G.; Disbrow, Gary L.; Kovacs, Gerald R.] Dept Hlth & Human Serv, Div CBRN Countermeasures, Off Secretary,BARDA, Off Assistant Secretary Preparedness & Response, Washington, DC 20201 USA.
[Cliffer, Kenneth D.; Prasher, Joanna M.] Dept Hlth & Human Serv, Div Med Countermeasure Strategy & Requirements, Off Policy & Planning,Off Secretary, Off Assistant Secretary Preparedness & Response, Washington, DC 20201 USA.
[Moyer, Brian R.] Tunnell Consulting Inc, King Of Prussia, PA 19406 USA.
[Coleman, C. Norman; Bader, Judith L.] Dept Hlth & Human Serv, Off Preparedness & Emergency Operat, Off Assistant Secretary Preparedness & Response, Off Secretary, Washington, DC 20201 USA.
[Coleman, C. Norman; Bader, Judith L.] NCI, NIH, Bethesda, MD 20892 USA.
[Mercier, John] Uniformed Serv Univ Hlth Sci, Armed Forces Radiobiol Res Inst, Bethesda, MD 20889 USA.
RP Grace, MB (reprint author), Dept Hlth & Human Serv, Div CBRN Countermeasures, Off Secretary,BARDA, Off Assistant Secretary Preparedness & Response, 330 Independence Ave SW,Room 644G, Washington, DC 20201 USA.
EM marcy.grace@hhs.gov
NR 31
TC 6
Z9 6
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0017-9078
EI 1538-5159
J9 HEALTH PHYS
JI Health Phys.
PD SEP
PY 2011
VL 101
IS 3
BP 238
EP 247
DI 10.1097/HP.0b013e3182135fba
PG 10
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 799EH
UT WOS:000293266100003
PM 21799340
ER
PT J
AU Bouville, A
AF Bouville, Andre
TI NCRP Report No. 163, Radiation Dose Reconstruction: Principles and
Practices
SO HEALTH PHYSICS
LA English
DT Book Review
C1 NCI, Bethesda, MD 20892 USA.
RP Bouville, A (reprint author), NCI, 6120 Execut Blvd,Room EPS-7094, Bethesda, MD 20892 USA.
EM BouvillA@mail.nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0017-9078
EI 1538-5159
J9 HEALTH PHYS
JI Health Phys.
PD SEP
PY 2011
VL 101
IS 3
BP 321
EP 321
DI 10.1097/HP.0b013e31820f8e30
PG 1
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 799EH
UT WOS:000293266100011
ER
PT J
AU Taylor, KC
Lange, LA
Zabaneh, D
Lange, E
Keating, BJ
Tang, W
Smith, NL
Delaney, JA
Kumari, M
Hingorani, A
North, KE
Kivimaki, M
Tracy, RP
O'Donnell, CJ
Folsom, AR
Green, D
Humphries, SE
Reiner, AP
AF Taylor, Kira C.
Lange, Leslie A.
Zabaneh, Delilah
Lange, Ethan
Keating, Brendan J.
Tang, Weihong
Smith, Nicholas L.
Delaney, Joseph A.
Kumari, Meena
Hingorani, Aroon
North, Kari E.
Kivimaki, Mika
Tracy, Russell P.
O'Donnell, Christopher J.
Folsom, Aaron R.
Green, David
Humphries, Steve E.
Reiner, Alexander P.
TI A gene-centric association scan for Coagulation Factor VII levels in
European and African Americans: the Candidate Gene Association Resource
(CARe) Consortium
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CORONARY-HEART-DISEASE; VON-WILLEBRAND-FACTOR;
CLOTTING FACTOR-VII; F7 GENE; CARDIOVASCULAR-DISEASE;
MYOCARDIAL-INFARCTION; ISCHEMIC-STROKE; ARTERY-DISEASE; PLASMA-LEVELS
AB Polymorphisms in several distinct genomic regions, including the F7 gene, were recently associated with factor VII (FVII) levels in European Americans (EAs). The genetic determinants of FVII in African Americans (AAs) are unknown. We used a 50 000 single nucleotide polymorphism (SNP) gene-centric array having dense coverage of over 2 000 candidate genes for cardiovascular disease (CVD) pathways in a community-based sample of 16 324 EA and 3898 AA participants from the Candidate Gene Association Resource (CARe) consortium. Our aim was the discovery of new genomic loci and more detailed characterization of existing loci associated with FVII levels. In EAs, we identified three new loci associated with FVII, of which APOA5 on chromosome 11q23 and HNF4A on chromosome 20q12-13 were replicated in a sample of 4289 participants from the Whitehall II study. We confirmed four previously reported FVII-associated loci (GCKR, MS4A6A, F7 and PROCR) in CARe EA samples. In AAs, the F7 and PROCR regions were significantly associated with FVII. Several of the FVII-associated regions are known to be associated with lipids and other cardiovascular-related traits. At the F7 locus, there was evidence of at least five independently associated SNPs in EAs and three independent signals in AAs. Though the variance in FVII explained by the existing loci is substantial (20% in EA and 10% in AA), larger sample sizes and investigation of lower frequency variants may be required to identify additional FVII-associated loci in EAs and AAs and further clarify the relationship between FVII and other CVD risk factors.
C1 [Taylor, Kira C.; North, Kari E.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27514 USA.
[Lange, Leslie A.; Lange, Ethan] Univ N Carolina, Sch Med, Dept Genet, Chapel Hill, NC 27514 USA.
[Zabaneh, Delilah] UCL, Genet Inst, Dept Genet Environm & Evolut, London WC1E 6JJ, England.
[Humphries, Steve E.] UCL, Inst Cardiovasc Sci, BHF Labs, Ctr Cardiovasc Genet, London WC1E 6JJ, England.
[Keating, Brendan J.] Childrens Hosp Philadelphia, Abramson Res Ctr, Ctr Appl Genom, Philadelphia, PA 19104 USA.
[Tang, Weihong; Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA.
[Smith, Nicholas L.; Reiner, Alexander P.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
[Delaney, Joseph A.] Univ Florida, Dept Pharmaceut Outcomes & Pharm, Coll Pharm, Gainesville, FL 32610 USA.
[Kumari, Meena; Kivimaki, Mika] London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London WC1E 7HT, England.
[Hingorani, Aroon] UCL, Dept Epidemiol & Publ Hlth, Genet Epidemiol Grp, London WC1E 6BT, England.
[Tracy, Russell P.] Univ Vermont, Dept Pathol & Lab Med, Coll Med, Burlington, VT 05405 USA.
[O'Donnell, Christopher J.] NHLBI, NIH, Bethesda, MD 20824 USA.
[Green, David] Northwestern Univ, Div Hematol Oncol, Feinberg Sch Med, Chicago, IL 60611 USA.
RP Taylor, KC (reprint author), Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, 137 E Franklin St,Suite 306, Chapel Hill, NC 27514 USA.
EM kirat@email.unc.edu
RI Kivimaki, Mika/B-3607-2012;
OI Kivimaki, Mika/0000-0002-4699-5627; Humphries, Stephen
E/0000-0002-8221-6547
FU National Heart, Lung and Blood Institute of the National Institutes of
Health [5T32HL007055-34]; Heart Lung and Blood Institute of the National
Institutes of Health [HL36310, HL71862-06]; National Institutes of
Health [HHSN268200625226C, N01HC65226-6-0-0]; National Institute of
Aging of the National Institutes of Health [AG032136, AG034454,
AG13196]; Agency for Health Care Policy Research [HS06516]; Medical
Research Council; Health and Safety Executive; John D. and Catherine T.
MacArthur Foundation Research Networks on Successful Midlife Development
and Socioeconomic Status and Health; BUPA Foundation; UCL Genetics
Institute; British Heart Foundation
FX This work was supported by the National Heart, Lung and Blood Institute
of the National Institutes of Health (#5T32HL007055-34); the Heart Lung
and Blood Institute of the National Institutes of Health (HL36310,
HL71862-06); the National Institutes of Health (HHSN268200625226C,
N01HC65226-6-0-0); the National Institute of Aging of the National
Institutes of Health (AG032136, AG034454, AG13196); the Agency for
Health Care Policy Research (HS06516); the Medical Research Council; the
Health and Safety Executive; and the John D. and Catherine T. MacArthur
Foundation Research Networks on Successful Midlife Development and
Socioeconomic Status and Health and the BUPA Foundation. D.Z. is funded
by the UCL Genetics Institute and S.E.H. by the British Heart
Foundation.
NR 53
TC 8
Z9 8
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD SEP 1
PY 2011
VL 20
IS 17
BP 3525
EP 3534
DI 10.1093/hmg/ddr264
PG 10
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 807NZ
UT WOS:000293907500018
PM 21676895
ER
PT J
AU Roman, MJ
Howard, BV
Howard, WJ
Mete, M
Fleg, JL
Lee, ET
Devereux, RB
AF Roman, Mary J.
Howard, Barbara V.
Howard, Wm. James
Mete, Mihriye
Fleg, Jerome L.
Lee, Elisa T.
Devereux, Richard B.
TI Differential Impacts of Blood Pressure and Lipid Lowering on Regression
of Ventricular and Arterial Mass The Stop Atherosclerosis in Native
Diabetics Trial
SO HYPERTENSION
LA English
DT Article
DE hypertrophy/remodeling; atherosclerosis; target organ damage
ID INTIMA-MEDIA THICKNESS; ASYMPTOMATIC CAROTID ATHEROSCLEROSIS;
DENSITY-LIPOPROTEIN CHOLESTEROL; EXTENDED-RELEASE NIACIN;
CORONARY-HEART-DISEASE; DOUBLE-BLIND; REDUCING CHOLESTEROL; VASCULAR
HYPERTROPHY; AMERICAN-SOCIETY; RANDOMIZED-TRIAL
AB The relative impacts of lowering blood pressure versus lowering low-density lipoprotein (LDL) cholesterol on regression of ventricular and arterial mass have not been systematically examined. Changes in left ventricular mass and arterial mass (common carotid artery cross-sectional area) after 36 months of simultaneous lowering of systolic blood pressure and LDL cholesterol were examined in the Stop Atherosclerosis in Native Diabetics Trial of standard versus aggressive LDL cholesterol and blood pressure targets in American Indians with type 2 diabetes mellitus. The 2 treatment groups were combined to examine changes in left ventricular and arterial mass over a spectrum of achieved blood pressure and lipid levels. Among the combined group of 413 Stop Atherosclerosis in Native Diabetics Trials participants, systolic blood pressure, LDL cholesterol, and left ventricular mass were all significantly reduced, whereas arterial mass significantly increased, after 36 months of therapy (P<0.001 for all). In linear regression models, a decrease in arterial mass was significantly related to achieved systolic blood pressure and, to a lesser extent, achieved LDL cholesterol, after adjustment for important covariates. Left ventricular mass progressively decreased with lower achieved levels of systolic blood pressure, independent of baseline levels of left ventricular mass. In conclusion, achieved levels of systolic blood pressure are important determinants of the extent of regression of arterial and ventricular mass during prolonged therapy in diabetic individuals. Achieved levels of LDL cholesterol influence regression of arterial but not ventricular mass. Our findings suggest that there is no threshold of systolic blood pressure below which regression of cardiovascular target organ damage cannot be achieved. (Hypertension. 2011;58:367-371.)
C1 [Roman, Mary J.; Devereux, Richard B.] Weill Cornell Med Coll, Div Cardiol, New York, NY 10021 USA.
[Fleg, Jerome L.] NHLBI, Bethesda, MD 20892 USA.
[Lee, Elisa T.] Univ Oklahoma, Hlth Sci Ctr, Ctr Amer Indian Hlth Res, Oklahoma City, OK USA.
[Howard, Barbara V.; Howard, Wm. James; Mete, Mihriye] Medstar Res Inst, Washington, DC USA.
RP Roman, MJ (reprint author), Weill Cornell Med Coll, Div Cardiol, 525 E 68th St, New York, NY 10021 USA.
EM mroman@med.cornell.edu
FU National Heart, Lung, and Blood Institute, National Institutes of Health
[1U01 HL67031-01A1]
FX Funding was provided by the National Heart, Lung, and Blood Institute,
National Institutes of Health, grant 1U01 HL67031-01A1. Medications were
donated by First Horizon Pharmacy (Triglide); Merck and Co
(Cozaar/Hyzaar); and Pfizer, Inc (Lipitor).
NR 37
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Z9 3
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD SEP
PY 2011
VL 58
IS 3
BP 367
EP 371
DI 10.1161/HYPERTENSIONAHA.111.172486
PG 5
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 808CN
UT WOS:000293952500014
PM 21788602
ER
PT J
AU Dulebohn, DP
Bestor, A
Rego, ROM
Stewart, PE
Rosa, PA
AF Dulebohn, Daniel P.
Bestor, Aaron
Rego, Ryan O. M.
Stewart, Philip E.
Rosa, Patricia A.
TI Borrelia burgdorferi Linear Plasmid 38 Is Dispensable for Completion of
the Mouse-Tick Infectious Cycle
SO INFECTION AND IMMUNITY
LA English
DT Article
ID LYME-DISEASE SPIROCHETE; OUTER SURFACE PROTEIN; CIRCULAR PLASMIDS;
GENE-EXPRESSION; SENSU-STRICTO; RESERVOIR COMPETENCE; MOLECULAR-BIOLOGY;
NORTH-AMERICA; GENOME; DNA
AB Borrelia burgdorferi, the causative agent of Lyme disease, exists in a complex enzootic cycle, transiting between its vector, Ixodes ticks, and a diverse range of vertebrate hosts. B. burgdorferi linear plasmid 38 (lp38) contains several genes that are differentially regulated in response to conditions mimicking the tick or mouse environments, suggesting that these plasmid-borne genes may encode proteins important for the B. burgdorferi infectious cycle. Some of these genes encode potential virulence factors, including hypothetical lipoproteins as well as a putative membrane transport system. To characterize the role of lp38 in the B. burgdorferi infectious cycle, we constructed a shuttle vector to selectively displace lp38 from the B. burgdorferi genome and analyzed the resulting clones to confirm the loss of lp38. We found that, in vitro, clones lacking lp38 were similar to isogenic wild-type bacteria, both in growth rate and in antigenic protein production. We analyzed these strains in an experimental mouse-tick infectious cycle, and our results demonstrate that clones lacking lp38 are fully infectious in a mouse, can efficiently colonize the tick vector, and are readily transmitted to a naive host.
C1 [Dulebohn, Daniel P.; Bestor, Aaron; Rego, Ryan O. M.; Stewart, Philip E.; Rosa, Patricia A.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, Div Intramural Res,NIH, Hamilton, MT 59840 USA.
RP Dulebohn, DP (reprint author), Natl Inst Infect Dis, Lab Zoonot Pathogens, Rocky Mt Labs, Div Intramural Res,NIH, Hamilton, MT 59840 USA.
EM dulebohnd@niaid.nih.gov
RI Rego, Ryan/G-9773-2014
OI Rego, Ryan/0000-0001-6932-0940
FU NIH, NIAID
FX This research was supported by the Intramural Research Program of the
NIH, NIAID.
NR 66
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U1 0
U2 0
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 2011
VL 79
IS 9
BP 3510
EP 3517
DI 10.1128/IAI.05014-11
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 807IV
UT WOS:000293891000004
PM 21708994
ER
PT J
AU Kalil, AC
Sun, JF
AF Kalil, Andre C.
Sun, Junfeng
TI Reply to Sprung et al: steroid treatment for patients with severe sepsis
and septic shock
SO INTENSIVE CARE MEDICINE
LA English
DT Letter
ID CORTICOSTEROIDS
C1 [Kalil, Andre C.] Univ Nebraska Med Ctr, Omaha, NE 68198 USA.
[Sun, Junfeng] NIH, Bethesda, MD 20892 USA.
RP Kalil, AC (reprint author), Univ Nebraska Med Ctr, Omaha, NE 68198 USA.
EM akalil@unmc.edu
NR 5
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0342-4642
J9 INTENS CARE MED
JI Intensive Care Med.
PD SEP
PY 2011
VL 37
IS 9
BP 1567
EP 1568
DI 10.1007/s00134-011-2294-1
PG 2
WC Critical Care Medicine
SC General & Internal Medicine
GA 807OI
UT WOS:000293908600031
ER
PT J
AU Kweon, O
Kim, SJ
Holland, RD
Chen, HY
Kim, DW
Gao, Y
Yu, LR
Baek, S
Baek, DH
Ahn, H
Cerniglia, CE
AF Kweon, Ohgew
Kim, Seong-Jae
Holland, Ricky D.
Chen, Hongyan
Kim, Dae-Wi
Gao, Yuan
Yu, Li-Rong
Baek, Songjoon
Baek, Dong-Heon
Ahn, Hongsik
Cerniglia, Carl E.
TI Polycyclic Aromatic Hydrocarbon Metabolic Network in Mycobacterium
vanbaalenii PYR-1
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID SP STRAIN PYR-1; RING-HYDROXYLATING OXYGENASES; DEGRADING MYCOBACTERIUM;
SYSTEMS-BIOLOGY; MOLECULAR CHARACTERIZATION; DEGRADATION PATHWAY; PYRENE
DEGRADATION; FUNCTIONAL MODULES; GROWTH SUBSTRATE; ORGANIZATION
AB This study investigated a metabolic network (MN) from Mycobacterium vanbaalenii PYR-1 for polycyclic aromatic hydrocarbons (PAHs) from the perspective of structure, behavior, and evolution, in which multilayer omics data are integrated. Initially, we utilized a high-throughput proteomic analysis to assess the protein expression response of M. vanbaalenii PYR-1 to seven different aromatic compounds. A total of 3,431 proteins (57.38% of the genome-predicted proteins) were identified, which included 160 proteins that seemed to be involved in the degradation of aromatic hydrocarbons. Based on the proteomic data and the previous metabolic, biochemical, physiological, and genomic information, we reconstructed an experiment-based system-level PAH-MN. The structure of PAH-MN, with 183 metabolic compounds and 224 chemical reactions, has a typical scale-free nature. The behavior and evolution of the PAH-MN reveals a hierarchical modularity with funnel effects in structure/function and intimate association with evolutionary modules of the functional modules, which are the ring cleavage process (RCP), side chain process (SCP), and central aromatic process (CAP). The 189 commonly upregulated proteins in all aromatic hydrocarbon treatments provide insights into the global adaptation to facilitate the PAH metabolism. Taken together, the findings of our study provide the hierarchical viewpoint from genes/proteins/metabolites to the network via functional modules of the PAH-MN equipped with the engineering-driven approaches of modularization and rationalization, which may expand our understanding of the metabolic potential of M. vanbaalenii PYR-1 for bioremediation applications.
C1 [Kweon, Ohgew; Kim, Seong-Jae; Kim, Dae-Wi; Cerniglia, Carl E.] Natl Ctr Toxicol Res FDA, Div Microbiol, Jefferson, AR 72079 USA.
[Kweon, Ohgew; Kim, Seong-Jae; Kim, Dae-Wi; Cerniglia, Carl E.] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Holland, Ricky D.; Gao, Yuan; Yu, Li-Rong] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Chen, Hongyan; Ahn, Hongsik] SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA.
[Baek, Songjoon] USN Hosp, NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20814 USA.
[Baek, Dong-Heon] Dankook Univ, Dept Oral Microbiol & Immunol, Sch Dent, Cheonan 330714, South Korea.
RP Cerniglia, CE (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM carl.cerniglia@fda.hhs.gov
FU U.S. Department of Energy; U.S. Food and Drug Administration
FX This work was supported in part by an appointment to the Postgraduate
Research Fellowship Program (D.K.) at the National Center for
Toxicological Research, administered by the Oak Ridge Institute for
Science and Education through an interagency agreement between the U.S.
Department of Energy and the U.S. Food and Drug Administration. The
views presented in this article do not necessarily reflect those of the
U.S. FDA.
NR 49
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Z9 34
U1 4
U2 49
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0021-9193
J9 J BACTERIOL
JI J. Bacteriol.
PD SEP
PY 2011
VL 193
IS 17
BP 4326
EP 4337
DI 10.1128/JB.00215-11
PG 12
WC Microbiology
SC Microbiology
GA 806EE
UT WOS:000293788300003
PM 21725022
ER
PT J
AU Preston, KL
Riley, P
Reamer, D
Schmittner, JP
Epstein, DH
Phillips, KA
AF Preston, Kenzie L.
Riley, Peter
Reamer, David
Schmittner, John P.
Epstein, David H.
Phillips, Karran A.
TI Effect of Methadone Maintenance on Body Mass Index and Lipid Profile in
a Cocaine- and Heroin-Using Population
SO JOURNAL OF CLINICAL PHARMACOLOGY
LA English
DT Meeting Abstract
C1 [Preston, Kenzie L.; Riley, Peter; Reamer, David; Schmittner, John P.; Epstein, David H.; Phillips, Karran A.] NIDA Intramural Res Program, Clin Pharmacol & Therapeut Res Branch, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0091-2700
J9 J CLIN PHARMACOL
JI J. Clin. Pharmacol.
PD SEP
PY 2011
VL 51
IS 9
BP 1329
EP 1329
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 806EM
UT WOS:000293789100020
ER
PT J
AU Harunaga, J
Hsu, JC
Yamada, KM
AF Harunaga, J.
Hsu, J. C.
Yamada, K. M.
TI Dynamics of Salivary Gland Morphogenesis
SO JOURNAL OF DENTAL RESEARCH
LA English
DT Review
DE developmental biology; cell-matrix interactions; microscopy; gene
expression; cell signaling; tissue engineering
ID MOUSE SUBMANDIBULAR-GLAND; ADENOVIRAL-MEDIATED TRANSFER; INCREASED FLUID
SECRETION; BRANCHING MORPHOGENESIS; DEVELOPING KIDNEY; AQUAPORIN-1 CDNA;
SYSTEMS-ANALYSIS; GENE-EXPRESSION; MYOSIN-II; CELL
AB Salivary glands form during embryonic development by a complex process that creates compact, highly organized secretory organs with functions essential for oral health. The architecture of these glands is generated by branching morphogenesis, revealed by recent research to involve unexpectedly dynamic cell motility and novel regulatory pathways. Numerous growth factors, extracellular matrix molecules, gene regulatory pathways, and mechanical forces contribute to salivary gland morphogenesis, but local gene regulation and morphological changes appear to play particularly notable roles. Here we review these recent advances and their potential application to salivary gland tissue engineering.
C1 [Harunaga, J.; Hsu, J. C.; Yamada, K. M.] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
RP Yamada, KM (reprint author), Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bldg 30,Room 426,30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA.
EM kenneth.yamada@nih.gov
OI Yamada, Kenneth/0000-0003-1512-6805
FU National Institute of Dental and Craniofacial Research
FX The authors acknowledge support from the Intramural Research Program of
the National Institute of Dental and Craniofacial Research. They declare
no potential conflicts of interest with respect to the authorship and/or
publication of this article.
NR 52
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U1 2
U2 12
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0022-0345
J9 J DENT RES
JI J. Dent. Res.
PD SEP
PY 2011
VL 90
IS 9
BP 1070
EP 1077
DI 10.1177/0022034511405330
PG 8
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 807FT
UT WOS:000293882400005
PM 21487116
ER
PT J
AU Musselmann, K
Green, JA
Sone, K
Hsu, JC
Bothwell, IR
Johnson, SA
Harunaga, JS
Wei, Z
Yamada, KM
AF Musselmann, K.
Green, J. A.
Sone, K.
Hsu, J. C.
Bothwell, I. R.
Johnson, S. A.
Harunaga, J. S.
Wei, Z.
Yamada, K. M.
TI Salivary Gland Gene Expression Atlas Identifies a New Regulator of
Branching Morphogenesis
SO JOURNAL OF DENTAL RESEARCH
LA English
DT Article
DE microarray; laser microdissection; branching morphogenesis; GSK3beta;
organ morphogenesis; gene expression
ID GLYCOGEN-SYNTHASE KINASE-3; SUBMANDIBULAR-GLAND; EMBRYONIC LUNG;
BETA-CATENIN; MOUSE; CELL; WNT; FIBRONECTIN; PHOSPHORYLATION; ELONGATION
AB During organ development, local changes in gene expression govern morphogenesis and cell fate. We have generated a microanatomical atlas of epithelial gene expression of embryonic salivary glands. The mouse submandibular salivary gland first appears as a single mass of epithelial cells surrounded by mesenchyme, and it undergoes rapid branching morphogenesis to form a complex secretory organ with acini connected to an extensive ductal system. Using laser capture microdissection, we collected samples from 14 distinct epithelial locations at embryonic days 12.5, 13.5, 14, and 15, and characterized their gene expression by microarray analysis. These microarray results were evaluated by qPCR of biological replicates and by comparisons of the gene expression dataset with published expression data. Using this gene expression atlas to search for novel regulators of branching morphogenesis, we found a substantial reduction in mRNA levels of GSK3 beta at the base of forming clefts. This unexpected finding was confirmed by immunostaining, and inhibition of GSK3 beta activity enhanced salivary gland branching. This first microanatomical expression atlas of a developing gland characterizes changes in local gene expression during salivary gland development and differentiation, which should facilitate the identification of key genes involved in tissue morphogenesis.
C1 [Musselmann, K.; Green, J. A.; Sone, K.; Hsu, J. C.; Bothwell, I. R.; Johnson, S. A.; Harunaga, J. S.; Yamada, K. M.] Natl Inst Dent & Craniofacial Res, Cell Biol Sect, Lab Cell & Dev Biol, Div Intramural Res, Bethesda, MD 20892 USA.
[Wei, Z.] Natl Inst Dent & Craniofacial Res, Dev Mech Sect, Div Intramural Res, Bethesda, MD 20892 USA.
RP Musselmann, K (reprint author), Natl Inst Dent & Craniofacial Res, Cell Biol Sect, Lab Cell & Dev Biol, Div Intramural Res, 30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA.
EM kurt.musselmann@gmail.com; kenneth.yamada@nih.gov
OI Yamada, Kenneth/0000-0003-1512-6805
FU Division of Intramural Research, National Institute of Dental and
Craniofacial Research, National Institutes of Health (Bethesda, MD, USA)
FX This work was supported by the Division of Intramural Research, National
Institute of Dental and Craniofacial Research, National Institutes of
Health (Bethesda, MD, USA). The authors declare no potential conflicts
of interest with respect to the authorship and/or publication of this
article.
NR 30
TC 12
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U1 0
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0022-0345
J9 J DENT RES
JI J. Dent. Res.
PD SEP
PY 2011
VL 90
IS 9
BP 1078
EP 1084
DI 10.1177/0022034511413131
PG 7
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 807FT
UT WOS:000293882400006
PM 21709141
ER
PT J
AU Wang, EA
McGinnis, KA
Fiellin, DA
Goulet, JL
Bryant, K
Gibert, CL
Leaf, DA
Mattocks, K
Sullivan, LE
Vogenthaler, N
Justice, AC
AF Wang, Emily A.
McGinnis, Kathleen A.
Fiellin, David A.
Goulet, Joseph L.
Bryant, Kendall
Gibert, Cynthia L.
Leaf, David A.
Mattocks, Kristin
Sullivan, Lynn E.
Vogenthaler, Nicholas
Justice, Amy C.
CA VACS Project Team
TI Food Insecurity is Associated with Poor Virologic Response among
HIV-Infected Patients Receiving Antiretroviral Medications
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE food insecurity; HIV; patients; antiretrovirals
ID HOUSING INSTABILITY; ALCOHOL-CONSUMPTION; WELFARE RECIPIENTS; PHARMACY
RECORDS; MENTAL-HEALTH; SAN-FRANCISCO; WEIGHT-LOSS; ADHERENCE; HIV/AIDS;
INSUFFICIENCY
AB BACKGROUND AND OBJECTIVE: Food insecurity negatively impacts HIV disease outcomes in international settings. No large scale U.S. studies have investigated the association between food insecurity and severity of HIV disease or the mechanism of this possible association. The objective of this study was to examine the impact of food insecurity on HIV disease outcomes in a large cohort of HIV-infected patients receiving antiretroviral medications.
DESIGN: This is a cross-sectional study.
PARTICIPANTS AND SETTING: Participants were HIV-infected patients enrolled in the Veterans Aging Cohort Study between 2002-2008 who were receiving antiretroviral medications.
MAIN MEASUREMENTS: Participants reporting "concern about having enough food for you or your family in the past 30 days" were defined as food insecure. Using multivariable logistic regression, we explored the association between food insecurity and both low CD4 counts (< 200 cells/mu L) and unsuppressed HIV-1 RNA (> 500 copies/mL). We then performed mediation analysis to examine whether antiretroviral adherence or body mass index mediates the observed associations.
KEY RESULTS: Among 2353 HIV-infected participants receiving antiretroviral medications, 24% reported food insecurity. In adjusted analyses, food insecure participants were more likely to have an unsuppressed HIV-1 RNA (AOR 1.37, 95% CI 1.09, 1.73) compared to food secure participants. Mediation analysis revealed that neither antiretroviral medication adherence nor body mass index contributes to the association between food insecurity and unsuppressed HIV-1 RNA. Food insecurity was not independently associated with low CD4 counts.
CONCLUSIONS: Among HIV-infected participants receiving antiretroviral medications, food insecurity is associated with unsuppressed viral load and may render treatment less effective. Longitudinal studies are needed to test the potential causal association between food insecurity, lack of virologic suppression, and additional HIV outcomes.
C1 [Wang, Emily A.; Fiellin, David A.; Goulet, Joseph L.; Mattocks, Kristin; Sullivan, Lynn E.; Justice, Amy C.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA.
[McGinnis, Kathleen A.] Pittsburgh VA Healthcare Syst, Pittsburgh, PA USA.
[Goulet, Joseph L.; Justice, Amy C.] VA Connecticut Healthcare Syst, West Haven, CT USA.
[Bryant, Kendall] NIAAA, NIH, Rockville, MD 20852 USA.
[Gibert, Cynthia L.] George Washington Univ, Med Ctr, Washington, DC 20037 USA.
[Gibert, Cynthia L.] VA Med Ctr, Washington, DC USA.
[Leaf, David A.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA.
[Vogenthaler, Nicholas] Emory Univ, Sch Med, Div Infect Dis, Atlanta, GA USA.
RP Wang, EA (reprint author), Yale Univ, Sch Med, Dept Internal Med, Harkness Hall Bldg A 367 Cedar St,Suite 410A, New Haven, CT 06510 USA.
EM emily.wang@yale.edu
RI Nguyen, Giang/D-9027-2016;
OI Goulet, Joseph/0000-0002-0842-804X; Fiellin, David/0000-0002-4006-010X
FU National Institute on Alcohol and Alcohol Abuse [U01 AA 13566, U10 AA
13566]; National Institute of Aging [K23 AG00826]; Robert Wood Johnson
Generalist Faculty Scholar Award; NIA; National Institute of Mental
Health; VA HSR&D Research Enhancement Award Program (REAP) PRIME Project
[REA 08-266]
FX This work was funded by National Institute on Alcohol and Alcohol Abuse
(U01 AA 13566 and U10 AA 13566), National Institute of Aging (K23
AG00826), Robert Wood Johnson Generalist Faculty Scholar Award, an
Inter-agency Agreement between NIA, National Institute of Mental Health,
and VA HSR&D Research Enhancement Award Program (REAP) PRIME Project
(REA 08-266). The views expressed in this article are those of the
authors and do not necessarily reflect the position or policy of the
Department of Veterans Affairs.
NR 36
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U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD SEP
PY 2011
VL 26
IS 9
BP 1012
EP 1018
DI 10.1007/s11606-011-1723-8
PG 7
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 808WW
UT WOS:000294013700015
PM 21573882
ER
PT J
AU Zeremski, M
Hooker, G
Shu, MA
Winkelstein, E
Brown, Q
Des Jarlais, DC
Tobler, LH
Rehermann, B
Busch, MP
Edlin, BR
Talal, AH
AF Zeremski, Marija
Hooker, Giles
Shu, Marla A.
Winkelstein, Emily
Brown, Queenie
Des Jarlais, Don C.
Tobler, Leslie H.
Rehermann, Barbara
Busch, Michael P.
Edlin, Brian R.
Talal, Andrew H.
TI Induction of CXCR3-and CCR5-associated chemokines during acute hepatitis
C virus infection
SO JOURNAL OF HEPATOLOGY
LA English
DT Article
DE CXCL9; CXCL10; CXCL11; CCL3; CCL4; Inflammation
ID INJECTION-DRUG USERS; IMMUNOLOGICAL DETERMINANTS; IMMUNE-RESPONSES;
PERSISTENCE; CHIMPANZEES; EVASION; DISEASE; INNATE; LIVER
AB Background & Aims: Characterization of inflammatory mediators, such as chemokines, during acute hepatitis C virus (HCV) infection might shed some light on viral clearance mechanisms.
Methods: Plasma levels of CXCR3 (CXCL9-11)- and CCR5 (CCL3-4)-associated chemokines, ALT, and HCV RNA were measured in nine injection drug users (median 26 samples/patient) before and during 10 acute (eight primary and two secondary) HCV infections. Using functional data analysis, we estimated smooth long-term trends in chemokine expression levels to obtain the magnitude and timing of overall changes. Residuals were analyzed to characterize short-term fluctuations.
Results: CXCL9-11 induction began 38-53 days and peaked 7283 days after virus acquisition. Increases in ALT levels followed a similar pattern. Substantial negative auto-correlations of chemokine levels at 1 week lags suggested substantial week-to-week oscillations. Significant correlations were observed between CXCL10 and HCV RNA as well as ALT and CXCR3-associated chemokines measured in the preceding week, CCL3-4 expression levels did not change appreciably during acute HCV infection.
Conclusions: Elevation of CXCR3-associated chemokines late during acute HCV infection suggests a role for cellular immune responses in chemokine induction. Week-to-week oscillations of HCV RNA, chemokines, and ALT suggest frequent, repeated cycles of gain and loss of immune control during acute hepatitis C. (C) 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
C1 [Zeremski, Marija; Shu, Marla A.; Winkelstein, Emily; Brown, Queenie; Edlin, Brian R.; Talal, Andrew H.] Weill Cornell Med Coll, Ctr Study Hepatitis C, New York, NY 10065 USA.
[Zeremski, Marija; Shu, Marla A.; Winkelstein, Emily; Brown, Queenie; Edlin, Brian R.; Talal, Andrew H.] Weill Cornell Med Coll, Div Gastroenterol & Hepatol, New York, NY 10065 USA.
[Hooker, Giles] Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY USA.
[Shu, Marla A.; Winkelstein, Emily; Edlin, Brian R.] State Univ New York Downstate Coll Med, Dept Med, Brooklyn, NY USA.
[Des Jarlais, Don C.] Beth Israel Deaconess Med Ctr, Baron Edmond Rothschild Chem Dependency Inst, New York, NY 10003 USA.
[Tobler, Leslie H.] Blood Syst Res Inst, San Francisco, CA USA.
[Rehermann, Barbara; Busch, Michael P.] NIDDK, Immunol Sect, Liver Dis Branch, NIH,DHHS, Bethesda, MD USA.
[Busch, Michael P.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
RP Talal, AH (reprint author), Weill Cornell Med Coll, Ctr Study Hepatitis C, 525 E 68th St,Box 319, New York, NY 10065 USA.
EM aht2002@med.cornell.edu
OI Edlin, Brian/0000-0001-8172-8797
FU NIH [R01-DA16159, R01-DA021550, UL1-RR024996]; Greenberg Foundation for
Medical Research; NIDDK, National Institutes of Health
FX We are grateful to the staff of the Lower East Side Harm Reduction
Coalition, and Kelly Szott for assistance with data and sample
collection, Lynn Mubita, Leeanne Stratton, Jessica Noack, Hanna
Alemayehu, and Queenie Brown for assistance with sample processing, and
Jihad Obeid, MD for assistance with data management. We also thank our
study participants for making this work possible. This work was
supported by NIH Grants R01-DA16159, R01-DA021550, UL1-RR024996, the
Greenberg Foundation for Medical Research, and the intramural research
program of NIDDK, National Institutes of Health.
NR 28
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Z9 21
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
J9 J HEPATOL
JI J. Hepatol.
PD SEP
PY 2011
VL 55
IS 3
BP 545
EP 553
DI 10.1016/j.jhep.2010.12.033
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 807VH
UT WOS:000293930600009
PM 21256906
ER
PT J
AU He, J
Gu, DF
Kelly, TN
Hixson, JE
Rao, DC
Jaquish, CE
Chen, J
Zhao, Q
Gu, C
Huang, JF
Shimmin, LC
Chen, JC
Mu, JJ
Ji, X
Liu, DP
Whelton, PK
AF He, Jiang
Gu, Dongfeng
Kelly, Tanika N.
Hixson, James E.
Rao, Dabeeru C.
Jaquish, Cashell E.
Chen, Jing
Zhao, Qi
Gu, Chi
Huang, Jianfeng
Shimmin, Lawrence C.
Chen, Ji-Chun
Mu, Jianjun
Ji, Xu
Liu, De-Pei
Whelton, Paul K.
CA GenSalt Collaborative Res Grp
TI Genetic variants in the renin-angiotensin-aldosterone system and blood
pressure responses to potassium intake
SO JOURNAL OF HYPERTENSION
LA English
DT Article
DE blood pressure; dietary potassium; genetic variants;
renin-angiotensin-aldosterone system
ID MINERALOCORTICOID RECEPTOR GENE; 11-BETA-HYDROXYSTEROID DEHYDROGENASE
TYPE-2; ESSENTIAL-HYPERTENSION; SALT SENSITIVITY; MOLECULAR-BASIS;
DIETARY-SODIUM; ASSOCIATION; POLYMORPHISMS; POPULATION; MECHANISMS
AB Objective Observational epidemiologic studies and clinical trials have documented that dietary potassium intake lowers blood pressure (BP). We examined the association between genetic variants in the renin-angiotensinaldosterone system and BP responses to potassium intervention.
Methods A 7-day high-sodium followed by a 7-day high-sodium plus 60 mmol/day potassium-supplementation feeding study was conducted among 1906 participants from rural northern China. Nine BP measurements were obtained at each intervention phase using a random-zero sphygmomanometer and 181 single-nucleotide polymorphisms (SNPs) in 11 candidate genes of the renin-angiotensin-aldosterone system were used for analyses.
Results Several SNPs in nuclear receptor subfamily 3, group C, member 2 (NR3C2), angiotensin II type 1 receptor (AGTR1), hydroxysteroid (11-beta) dehydrogenase 1 (HSD11B1), and hydroxysteroid (11-beta) dehydrogenase 2 (HSD11B2) genes were significantly associated with BP responses to potassium intervention. For example, the number of G alleles of the N554S missense mutation (rs5527) of NR3C2 was significantly associated with greater SBP responses to potassium intervention; mean [95% confidence interval (CI)] responses (mmHg) were -3.33 (-3.65 to -3.02) for genotype A/A and -5.47 (-6.64 to -4.29) for A/G, respectively (P value = 0.0004). In addition, the number of C alleles of the A1166C variant (rs5186) in AGTR1 was significantly and inversely associated with SBP responses to potassium intervention; mean (95% CI) responses were -3.55 (-3.87 to -3.24) for genotype A/A, -2.45 (-3.27 to -1.62) for A/C, and 3.25 (-5.73 to 12.23) for CC (P value = 0.003).
Conclusion These novel findings indicated that genetic variants in the renin-angiotensin-aldosterone system may play an important role in determining an individual's BP responses to dietary potassium intake. J Hypertens 29:1719-1730 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [He, Jiang; Kelly, Tanika N.; Zhao, Qi] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA 70112 USA.
[He, Jiang; Chen, Ji-Chun] Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70112 USA.
[Gu, Dongfeng; Gu, Chi; Huang, Jianfeng; Chen, Ji-Chun] Chinese Acad Med Sci, Fuwai Hosp, Beijing 100730, Peoples R China.
[Gu, Dongfeng; Gu, Chi; Huang, Jianfeng; Chen, Ji-Chun] Chinese Acad Med Sci, Cardiovasc Inst, Beijing 100730, Peoples R China.
[Gu, Dongfeng; Gu, Chi; Huang, Jianfeng; Chen, Ji-Chun] Peking Union Med Coll, Natl Ctr Cardiovasc Dis, Beijing 100021, Peoples R China.
[Hixson, James E.; Shimmin, Lawrence C.] Univ Texas Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX USA.
[Rao, Dabeeru C.; Gu, Chi] Washington Univ, Sch Med, Dept Biostat, St Louis, MO USA.
[Jaquish, Cashell E.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Mu, Jianjun] Xi An Jiao Tong Univ, Sch Med, Dept Med, Xian, Shanxi, Peoples R China.
[Liu, De-Pei] Chinese Acad Med Sci, Natl Lab Med Mol Biol, Inst Basic Med Sci, Beijing 100730, Peoples R China.
[Liu, De-Pei] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Whelton, Paul K.] Loyola Univ, Med Ctr, Off President, Maywood, IL 60153 USA.
RP He, J (reprint author), Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, 1440 Canal St,Suite 2000, New Orleans, LA 70112 USA.
EM jhe@tulane.edu
RI Gu, Charles/A-7934-2010
OI Gu, Charles/0000-0002-8527-8145
FU National Heart, Lung, and Blood Institute, National Institutes of
Health, Bethesda, Maryland [U01HL072507, R01HL087263, R01HL090682]
FX The Genetic Epidemiology Network of Salt Sensitivity (GenSalt) is
supported by research grants (U01HL072507, R01HL087263, and R01HL090682)
from the National Heart, Lung, and Blood Institute, National Institutes
of Health, Bethesda, Maryland. The GenSalt investigators acknowledge
Upsher-Smith Laboratories Inc. for providing potassium chloride tablets
(Klor-ConM20).
NR 30
TC 10
Z9 12
U1 0
U2 9
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 2011
VL 29
IS 9
BP 1719
EP 1730
DI 10.1097/HJH.0b013e32834a4d1f
PG 12
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 806QS
UT WOS:000293825600008
PM 21799445
ER
PT J
AU Sachs, DH
Cone, JL
AF Sachs, David H.
Cone, James L.
TI A MOUSE B-CELL ALLOANTIGEN DETERMINED BY GENE(S) LINKED TO THE MAJOR
HISTOCOMPATIBILITY COMPLEX
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID LYMPHOID-CELLS; BONE MARROW; ANTIGENS; IMMUNOGLOBULIN; LYMPHOCYTES;
SURFACE; MICE; THETA
AB The humoral response to transplantation across species includes the production of antibodies specific for the major histocompatibility alloantigens of the donor animal (1-3). In particular, rats immunized with mouse tissues have been shown to produce antibodies reactive against a number of individual H-2 specificities (1). One possible advantage of this method of production of cytotoxic antisera is the possibility that rats may respond to histocompatibility alloantigens not detected by other mice, thus providing new genetic markers.
In the course of analyzing antisera from a series of cross-species immunizations, and unexpected cytotoxic reaction with C57Bl/10 lymph node cells was observed with an antiserum which, according to the current H-2 chart, should have contained only specificity for H-2.31. The results of additional studies indicate: (a) that immunizations between appropriate congenic mouse strains produce alloimmune antisera which likewise detect this new specificity, (b) that these cytotoxic antisera (hereafter called anti-"beta") detect a cell-surface antigens(s) (hereafter called "beta") expressed preferentially on B cells, and (c) that tests of recombinant strains indicate that the gene(s) determining beta are linked to the K-end of the H-2 complex; i.e., in or to the left of the Ir-1 region.
C1 [Sachs, David H.; Cone, James L.] NCI, Immunol Branch, NIH, Bethesda, MD 20014 USA.
RP Sachs, DH (reprint author), NCI, Immunol Branch, NIH, Bethesda, MD 20014 USA.
NR 34
TC 0
Z9 0
U1 0
U2 0
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 2011
VL 187
IS 5
BP 1289
EP 1304
PG 16
WC Immunology
SC Immunology
GA 809MD
UT WOS:000294059500005
ER
PT J
AU Gibbons, DL
Abeler-Dorner, L
Raine, T
Hwang, IY
Jandke, A
Wencker, M
Deban, L
Rudd, CE
Irving, PM
Kehrl, JH
Hayday, AC
AF Gibbons, Deena L.
Abeler-Doerner, Lucie
Raine, Tim
Hwang, Il-Young
Jandke, Anett
Wencker, Melanie
Deban, Livija
Rudd, Christopher E.
Irving, Peter M.
Kehrl, John H.
Hayday, Adrian C.
TI Cutting Edge: Regulator of G Protein Signaling-1 Selectively Regulates
Gut T Cell Trafficking and Colitic Potential
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID INTRAEPITHELIAL LYMPHOCYTES; CELIAC-DISEASE; B-LYMPHOCYTES; RESPONSES;
RGS1; MICE; INFLAMMATION; MIGRATION; VARIANTS
AB The RGS1 gene is associated with celiac disease, multiple sclerosis, and type I diabetes, which are all T cell-mediated pathologies, yet there is no reported analysis of regulator of G protein signaling (RGS)1 biology in human T cells. This study shows that RGS1 expression is substantially higher in T cells from human gut versus peripheral blood and that this can be exaggerated in intestinal inflammation. Elevated RGS1 levels profoundly reduce T cell migration to lymphoid-homing chemokines, whereas RGS1 depletion selectively enhances such chemotaxis in gut T cells and impairs their colitogenic potential. These findings provide a revised framework in which to view the linkage of RGS1 to inflammatory disease. The Journal of Immunology, 2011, 187: 2067-2071.
C1 [Hayday, Adrian C.] Kings Coll London, Sch Med, Guys Hosp, Natl Inst Hlth Res,Biomed Res Ctr, London SE1 9RT, England.
[Gibbons, Deena L.; Abeler-Doerner, Lucie; Raine, Tim; Wencker, Melanie; Deban, Livija; Hayday, Adrian C.] Kings Coll London, Peter Gorer Dept Immunobiol, London SE1 9RT, England.
[Raine, Tim; Rudd, Christopher E.] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England.
[Hwang, Il-Young; Kehrl, John H.] NIH, Bethesda, MD 20892 USA.
[Jandke, Anett; Wencker, Melanie; Deban, Livija; Hayday, Adrian C.] London Res Inst, London WC2A 3LY, England.
RP Hayday, AC (reprint author), Kings Coll London, Sch Med, Guys Hosp, Natl Inst Hlth Res,Biomed Res Ctr, 2nd Floor,Borough Wing, London SE1 9RT, England.
EM adrian.hayday@kcl.ac.uk
RI Wencker, Melanie/M-3849-2014;
OI Wencker, Melanie/0000-0003-4200-0079; Kehrl, John/0000-0002-6526-159X
FU National Institute for Health Research Comprehensive Biomedical Research
Centre; Wellcome Trust; Marie Curie fellowship programme; National
Institutes of Health
FX This work was supported by the National Institute for Health Research
Comprehensive Biomedical Research Centre award to Guy's and St. Thomas'
National Health Service Foundation Trust in partnership with King's
College London and King's College Hospital National Health Service
Foundation Trust; The Wellcome Trust; the Marie Curie fellowship
programme; and the National Institutes of Health.
NR 19
TC 18
Z9 18
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 2011
VL 187
IS 5
BP 2067
EP 2071
DI 10.4049/jimmunol.1100833
PG 5
WC Immunology
SC Immunology
GA 809MD
UT WOS:000294059500007
PM 21795595
ER
PT J
AU O'Connor, GM
Yamada, E
Rampersaud, A
Thomas, R
Carrington, M
McVicar, DW
AF O'Connor, Geraldine M.
Yamada, Eriko
Rampersaud, Andy
Thomas, Rasmi
Carrington, Mary
McVicar, Daniel W.
TI Analysis of Binding of KIR3DS1*014 to HLA Suggests Distinct Evolutionary
History of KIR3DS1
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CELL INHIBITORY RECEPTOR; MHC CLASS-I; IMMUNOGLOBULIN-LIKE RECEPTORS;
NK-CELLS; PERIPHERAL-BLOOD; CUTTING EDGE; RECOGNITION; MOLECULES; GENE;
KIR
AB NK cell activity is regulated by the integration of positive and negative signals. One important source of these signals for human NK cells is the killer Ig-like receptor (KIR) family, which includes both members that transduce positive and those that generate negative signals. KIR3DL1 inhibits NK cell activity upon engagement by its ligand HLA-Bw4. The highly homologous KIR3DS1 is an activating receptor, which is implicated in the outcome of a variety of pathological situations. However, unlike KIR3DL1, direct binding of KIR3DS1(+) cells to HLA has not been demonstrated. We analyzed four key amino acid differences between KIR3DL1*01502 and KIR3DS1*013 to determine their role in KIR binding to HLA. Single substitutions of these residues dramatically reduced binding by KIR3DL1. In the reciprocal experiment, we found that the rare KIR3DS1 allotype KIR3DS1*014 binds HLA-Bw4 even though it differs from KIR3DS1*013 at only one of these positions (position 138). This reactivity was unexpectedly dependent on residues at other variable positions, as HLA-Bw4 binding was lost in receptors with KIR3DL1-like residues at both positions 199 and 138. These data provide the first evidence, to our knowledge, for the direct binding of KIR3DS1(+) cells to HLA-Bw4 and highlight the key role for position 138 in determining ligand specificity of KIR3DS1. They also reveal that KIR3DS1 reactivity and specificity is dictated by complex interactions between the residues in this region, suggesting a unique functional evolution of KIR3DS1 within the activating KIR family. The Journal of Immunology, 2011, 187: 2162-2171.
C1 [Thomas, Rasmi; Carrington, Mary; McVicar, Daniel W.] NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick, Frederick, MD 21702 USA.
[Thomas, Rasmi; Carrington, Mary] Ragon Inst MGH MIT & Harvard, Boston, MA 02114 USA.
RP McVicar, DW (reprint author), NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick, Bldg 560,Room 31-50, Frederick, MD 21702 USA.
EM mcvicard@mail.nih.gov
RI McVicar, Daniel/G-1970-2015
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research; National Cancer Institute, National Institutes of
Health [HHSN261200800001E]
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health, National Cancer Institute, Center for
Cancer Research. This work has been funded in part with federal funds
from the National Cancer Institute, National Institutes of Health, under
Contract HHSN261200800001E.
NR 37
TC 16
Z9 16
U1 0
U2 1
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD SEP 1
PY 2011
VL 187
IS 5
BP 2162
EP 2171
DI 10.4049/jimmunol.1002906
PG 10
WC Immunology
SC Immunology
GA 809MD
UT WOS:000294059500020
PM 21804024
ER
PT J
AU Sharda, DR
Yu, S
Ray, M
Squadrito, ML
De Palma, M
Wynn, TA
Morris, SM
Hankey, PA
AF Sharda, Daniel R.
Yu, Shan
Ray, Manujendra
Squadrito, Mario Leonardo
De Palma, Michele
Wynn, Thomas A.
Morris, Sidney M., Jr.
Hankey, Pamela A.
TI Regulation of Macrophage Arginase Expression and Tumor Growth by the Ron
Receptor Tyrosine Kinase
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID STIMULATING PROTEIN; NITRIC-OXIDE; IFN-GAMMA; DIFFERENTIAL REGULATION;
PERITONEAL-MACROPHAGES; ARGININE METABOLISM; ALTERED EXPRESSION;
SUPPRESSOR-CELLS; DENDRITIC CELLS; INNATE IMMUNITY
AB M1 activation of macrophages promotes inflammation and immunity to intracellular pathogens, whereas M2 macrophage activation promotes resolution of inflammation, wound healing, and tumor growth. These divergent phenotypes are characterized, in part, by the expression of inducible NO synthase and arginase I (Arg1) in M1 versus M2 activated macrophages, respectively. In this study, we demonstrate that the Ron receptor tyrosine kinase tips the balance of macrophage activation by attenuating the M1 phenotype while promoting expression of Arg1 through a Stat6-independent mechanism. Induction of the Arg1 promoter by Ron is mediated by an AP-1 site located 433 bp upstream of the transcription start site. Treatment of primary macrophages with macrophage stimulating protein, the ligand for Ron, induces potent MAPK activation, upregulates Fos, and enhances binding of Fos to the AP-1 site in the Arg1 promoter. In vivo, Arg1 expression in tumor-associated macrophages (TAMs) from Ron(-/-) mice was significantly reduced compared with that in TAMs from control animals. Furthermore, we show that Ron is expressed specifically by Tie2-expressing macrophages, a TAM subset that exhibits a markedly skewed M2 and protumoral phenotype. Decreased Arg1 in TAMs from Ron(-/-) mice was associated with reduced syngeneic tumor growth in these animals. These findings indicate that Ron induces Arg1 expression in macrophages through a previously uncharacterized AP-1 site in the Arg1 promoter and that Ron could be therapeutically targeted in the tumor microenvironment to inhibit tumor growth by targeting expression of Arg1. The Journal of Immunology, 2011, 187: 2181-2192.
C1 [Sharda, Daniel R.; Hankey, Pamela A.] Penn State Univ, Dept Vet & Biomed Sci, Grad Program Pathobiol, University Pk, PA 16802 USA.
[Yu, Shan; Hankey, Pamela A.] Penn State Univ, Dept Vet & Biomed Sci, Grad Program Physiol, University Pk, PA 16802 USA.
[Ray, Manujendra] Penn State Univ, Dept Vet & Biomed Sci, Grad Program Immunol & Infect Dis, University Pk, PA 16802 USA.
[Squadrito, Mario Leonardo; De Palma, Michele] Ist Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy, Angiogenesis & Tumor Targeting Unit, I-20132 Milan, Italy.
[Squadrito, Mario Leonardo; De Palma, Michele] Univ Vita Salute San Raffaele, I-20132 Milan, Italy.
[Wynn, Thomas A.] NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Morris, Sidney M., Jr.] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA 15219 USA.
RP Hankey, PA (reprint author), Penn State Univ, Dept Vet & Biomed Sci, Grad Program Pathobiol, 115 Henning Bldg, University Pk, PA 16802 USA.
EM phc7@psu.edu
RI Wynn, Thomas/C-2797-2011; Morris, Sidney/I-3440-2015; De Palma,
Michele/L-5350-2016
FU American Heart Association [09GRNT2390164]; National Institutes of
Health [R01 GM57384]
FX This work was supported by Grant 09GRNT2390164 from the American Heart
Association and Grant R01 GM57384 from the National Institutes of
Health.
NR 45
TC 46
Z9 49
U1 0
U2 11
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD SEP 1
PY 2011
VL 187
IS 5
BP 2181
EP 2192
DI 10.4049/jimmunol.1003460
PG 12
WC Immunology
SC Immunology
GA 809MD
UT WOS:000294059500022
PM 21810604
ER
PT J
AU Novikov, A
Cardone, M
Thompson, R
Shenderov, K
Kirschman, KD
Mayer-Barber, KD
Myers, TG
Rabin, RL
Trinchieri, G
Sher, A
Feng, CG
AF Novikov, Aleksey
Cardone, Marco
Thompson, Robert
Shenderov, Kevin
Kirschman, Kevin D.
Mayer-Barber, Katrin D.
Myers, Timothy G.
Rabin, Ronald L.
Trinchieri, Giorgio
Sher, Alan
Feng, Carl G.
TI Mycobacterium tuberculosis Triggers Host Type I IFN Signaling To
Regulate IL-1 beta Production in Human Macrophages
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID PEGYLATED INTERFERON-ALPHA; INFLAMMASOME ACTIVATION; PULMONARY
TUBERCULOSIS; INFECTED MACROPHAGES; GENE-EXPRESSION; DENDRITIC CELLS;
IMMUNE-SYSTEM; BOVIS BCG; INDUCTION; GAMMA
AB Mycobacterium tuberculosis is a virulent intracellular pathogen that survives in macrophages even in the presence of an intact adaptive immune response. Type I IFNs have been shown to exacerbate tuberculosis in mice and to be associated with disease progression in infected humans. Nevertheless, the mechanisms by which type I IFNs regulate the host response to M. tuberculosis infection are poorly understood. In this study, we show that M. tuberculosis induces an IFN-related gene expression signature in infected primary human macrophages, which is dependent on host type I IFN signaling as well as the mycobacterial virulence factor, region of difference-1. We further demonstrate that type I IFNs selectively limit the production of IL-1 beta, a critical mediator of immunity to M. tuberculosis. This regulation occurs at the level of IL1B mRNA expression, rather than caspase-1 activation or autocrine IL-1 amplification and appears to be preferentially used by virulent mycobacteria since avirulent M. bovis bacillus Calmette-Guerin (BCG) fails to trigger significant expression of type I IFNs or release of mature IL-1 beta protein. The latter property is associated with decreased caspase-1-dependent IL-1 beta maturation in the BCG-infected macrophages. Interestingly, human monocytes in contrast to macrophages produce comparable levels of IL-1 beta in response to either M. tuberculosis or BCG. Taken together, these findings demonstrate that virulent and avirulent mycobacteria employ distinct pathways for regulating IL-1 beta production in human macrophages and reveal that in the case of M. tuberculosis infection the induction of type I IFNs is a major mechanism used for this purpose. The Journal of Immunology, 2011, 187:2540-2547.
C1 [Novikov, Aleksey; Thompson, Robert; Shenderov, Kevin; Mayer-Barber, Katrin D.; Trinchieri, Giorgio; Sher, Alan; Feng, Carl G.] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Novikov, Aleksey] Howard Hughes Med Inst, Howard Hughes Med Inst Natl Inst Hlth Res Scholar, Chevy Chase, MD 20892 USA.
[Novikov, Aleksey] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA.
[Cardone, Marco; Trinchieri, Giorgio] NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Shenderov, Kevin; Rabin, Ronald L.] US FDA, Lab Immunobiochem, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Myers, Timothy G.] NIAID, Res & Technol Branch, NIH, Bethesda, MD 20892 USA.
RP Feng, CG (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Room 6142,Bldg 50,50 South Dr,MSC 8003, Bethesda, MD 20892 USA.
EM cfeng@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Department of Health and Human Services
FX This research was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Department of Health and Human Services.
NR 49
TC 86
Z9 87
U1 1
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 2011
VL 187
IS 5
BP 2540
EP 2547
DI 10.4049/jimmunol.1100926
PG 8
WC Immunology
SC Immunology
GA 809MD
UT WOS:000294059500057
PM 21784976
ER
PT J
AU Kang, JG
Amar, MJ
Remaley, AT
Kwon, J
Blackshear, PJ
Wang, PY
Hwang, PM
AF Kang, Ju-Gyeong
Amar, Marcelo J.
Remaley, Alan T.
Kwon, Jaeyul
Blackshear, Perry J.
Wang, Ping-yuan
Hwang, Paul M.
TI Zinc Finger Protein Tristetraprolin Interacts with CCL3 mRNA and
Regulates Tissue Inflammation
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID NECROSIS-FACTOR-ALPHA; RHEUMATOID-ARTHRITIS; GENE-EXPRESSION; DEFICIENT
MICE; TNF-ALPHA; ATHEROSCLEROSIS; CHEMOKINES; DISEASE; CELLS; STABILITY
AB Zinc finger protein tristetraprolin (TTP) modulates macrophage inflammatory activity by destabilizing cytokine mRNAs. In this study, through a screen of TTP-bound mRNAs in activated human macrophages, we have identified CCL3 mRNA as the most abundantly bound TTP target mRNA and have characterized this interaction via conserved AU-rich elements. Compared to the wild-type cells, TTP(-/-) macrophages produced higher levels of LPS-induced CCL3. In addition, the plasma level of CCL3 in TTP(-/-) mice was markedly higher than that in wild-type mice. To determine the in vivo significance of TTP-regulated CCL3, we generated CCL3(-/-) TTP(-/-) double-knockout mice. Along with decreased proinflammatory cytokines in their paw joints, there were significant functional and histologic improvements in the inflammatory arthritis of TTP(-/-) mice when CCL3 was absent, although cachexia, reflecting systemic inflammation, was notably unaffected. Furthermore, the marked exacerbation of aortic plaque formation caused by TTP deficiency in the APOE(-/-) mouse model of atherosclerosis was also rescued by disrupting CCL3. Taken together, our data indicate that the interaction between TTP and CCL3 mRNA plays an important role in modulating localized inflammatory processes in tissues that are dissociated from the systemic manifestations of chronic inflammation. The Journal of Immunology, 2011, 187: 2696-2701.
C1 [Kang, Ju-Gyeong; Wang, Ping-yuan; Hwang, Paul M.] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA.
[Amar, Marcelo J.; Remaley, Alan T.] NHLBI, Cardiopulm Branch, NIH, Bethesda, MD 20892 USA.
[Kwon, Jaeyul] NIAID, Lab Host Defenses, NIH, Bethesda, MD 20892 USA.
[Blackshear, Perry J.] NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA.
RP Hwang, PM (reprint author), NHLBI, Ctr Mol Med, NIH, Bldg 10 CRC,Room 5-5330,10 Ctr Dr, Bethesda, MD 20892 USA.
EM hwangp@mail.nih.gov
FU Division of Intramural Research, National Heart, Lung, and Blood
Institute, National Institutes of Health
FX This work was supported by funds from the Division of Intramural
Research, National Heart, Lung, and Blood Institute, National Institutes
of Health.
NR 43
TC 17
Z9 17
U1 0
U2 2
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 2011
VL 187
IS 5
BP 2696
EP 2701
DI 10.4049/jimmunol.1101149
PG 6
WC Immunology
SC Immunology
GA 809MD
UT WOS:000294059500073
PM 21784977
ER
PT J
AU Falkenburg, WJJ
Melenhorst, JJ
van de Meent, M
Kester, MGD
Hombrink, P
Heemskerk, MHM
Hagedoorn, RS
Gostick, E
Price, DA
Falkenburg, JHF
Barrett, AJ
Jedema, I
AF Falkenburg, Willem J. J.
Melenhorst, J. Joseph
van de Meent, Marian
Kester, Michel G. D.
Hombrink, Pleun
Heemskerk, Mirjam H. M.
Hagedoorn, Renate S.
Gostick, Emma
Price, David A.
Falkenburg, J. H. Frederik
Barrett, A. John
Jedema, Inge
TI Allogeneic HLA-A*02-Restricted WT1-Specific T Cells from Mismatched
Donors Are Highly Reactive but Show Off-Target Promiscuity
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID TUMOR GENE WT1; ACUTE MYELOID-LEUKEMIA; HLA CLASS-I; HIGH-AVIDITY;
PEPTIDE VACCINATION; DENDRITIC CELLS; MYELODYSPLASTIC SYNDROME;
ANTITUMOR-ACTIVITY; COMPLETE REMISSION; HEALTHY DONORS
AB T cells recognizing tumor-associated Ags such as Wilms tumor protein (WT1) are thought to exert potent antitumor reactivity. However, no consistent high-avidity T cell responses have been demonstrated in vaccination studies with WT1 as target in cancer immunotherapy. The aim of this study was to investigate the possible role of negative thymic selection on the avidity and specificity of T cells directed against self-antigens. T cell clones directed against the HLA-A*0201-binding WT1(126-134) peptide were generated from both HLA-A*02-positive (self-HLA-restricted) and HLA-A*02-negative [nonself (allogeneic) HLA [allo-HLA]-restricted] individuals by direct ex vivo isolation using tetramers or after in vitro priming and selection. The functional avidity and specificity of these T cell clones was analyzed in-depth. Self-HLA-restricted WT1-specific clones only recognized WT1(126-134) with low avidities. In contrast, allo-HLA-restricted WT1 clones exhibited profound functional reactivity against a multitude of HLAA*02-positive targets, even in the absence of exogenously loaded WT1 peptide, indicative of Ag-binding promiscuity. To characterize this potential promiscuity, reactivity of the T cell clones against 400 randomly selected HLA-A*0201-binding peptides was investigated. The self-HLA-restricted WT1-specific T cell clones only recognized the WT1 peptide. In contrast, the allo-HLA-restricted WT1-reactive clones recognized besides WT1 various other HLA-A*0201-binding peptides. In conclusion, allogeneic HLA-A*02-restricted WT1-specific T cells isolated from mismatched donors may be more tumor-reactive than their autologous counterparts but can show specific off-target promiscuity of potential clinical importance. As a result of this, administration of WT1-specific T cells generated from HLA-mismatched donors should be performed with appropriate precautions against potential off-target effects. The Journal of Immunology, 2011, 187: 2824-2833.
C1 [van de Meent, Marian; Kester, Michel G. D.; Hombrink, Pleun; Heemskerk, Mirjam H. M.; Hagedoorn, Renate S.; Falkenburg, J. H. Frederik; Jedema, Inge] Leiden Univ, Med Ctr, Dept Hematol, NL-2300 RC Leiden, Netherlands.
[Falkenburg, Willem J. J.; Melenhorst, J. Joseph; Barrett, A. John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Gostick, Emma; Price, David A.] Cardiff Univ, Sch Med, Dept Infect Immun & Biochem, Cardiff CF14 4XN, S Glam, Wales.
RP Jedema, I (reprint author), Univ Med Ctr, Dept Hematol, C2R-140,POB 9600, NL-2300 RC Leiden, Netherlands.
EM i.jedema@lumc.nl
RI Price, David/C-7876-2013
OI Price, David/0000-0001-9416-2737
FU Medical Research Council [G0501963]
NR 59
TC 21
Z9 22
U1 0
U2 2
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 2011
VL 187
IS 5
BP 2824
EP 2833
DI 10.4049/jimmunol.1100852
PG 10
WC Immunology
SC Immunology
GA 809MD
UT WOS:000294059500087
PM 21821799
ER
PT J
AU Bottalico, D
Chen, ZG
Dunne, A
Ostoloza, J
McKinney, S
Sun, C
Schlecht, NF
Fatahzadeh, M
Herrero, R
Schiffman, M
Burk, RD
AF Bottalico, Danielle
Chen, Zigui
Dunne, Anne
Ostoloza, Janae
McKinney, Sharod
Sun, Chang
Schlecht, Nicolas F.
Fatahzadeh, Mahnaz
Herrero, Rolando
Schiffman, Mark
Burk, Robert D.
TI The Oral Cavity Contains Abundant Known and Novel Human Papillomaviruses
From the Betapapillomavirus and Gammapapillomavirus Genera
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; SQUAMOUS-CELL CARCINOMA; SEXUAL-BEHAVIOR;
NATURAL-HISTORY; CERVICAL-CANCER; HEALTHY SKIN; RISK-FACTORS; INFECTION;
PREVALENCE; ADULTS
AB Background. Human papillomaviruses (HPVs) primarily sort into 3 genera: Alphapapillomavirus (alpha-HPV), predominantly isolated from mucosa, and Betapapillomavirus (beta-HPV) and Gammapapillomavirus (gamma-HPV), predominantly isolated from skin. HPV types might infect body sites that are different from those from which they were originally isolated.
Methods. We investigated the spectrum of HPV type distribution in oral rinse samples from 2 populations: 52 human immunodeficiency virus (HIV)-positive men and women and 317 men who provided a sample for genomic DNA for a prostate cancer study. HPV types were detected with the MY09/MY11 and FAP59/64 primer systems and identified by dot blot hybridization and/or direct sequencing.
Results. Oral rinse specimens from 35 (67%) of 52 HIV-positive individuals and 117 (37%) of 317 older male participants tested positive for HPV DNA. We found 117 type-specific HPV infections from the HIV-positive individuals, including 73 alpha-HPV, 33 beta-HPV, and 11 gamma-HPV infections; whereas, the distribution was 46 alpha-HPV, 108 beta-HPV, and 14 gamma-HPV infections from 168 type-specific infections from the 317 male participants.
Conclusions. The oral cavity contains a wide spectrum of HPV types predominantly from the beta-HPV and gamma-HPV genera, which were previously considered to be cutaneous types. These results could have significant implications for understanding the biology of HPV and the epidemiological associations of HPV with oral and skin neoplasia.
C1 [Burk, Robert D.] Albert Einstein Coll Med, Albert Einstein Canc Ctr, Bronx, NY 10461 USA.
[Bottalico, Danielle; Chen, Zigui; Dunne, Anne; Ostoloza, Janae; McKinney, Sharod; Burk, Robert D.] Univ Med & Dent New Jersey, New Jersey Dent Sch, Dept Pediat, Newark, NJ 07103 USA.
[Chen, Zigui; Sun, Chang; Burk, Robert D.] Univ Med & Dent New Jersey, New Jersey Dent Sch, Dept Microbiol & Immunol, Newark, NJ 07103 USA.
[Schlecht, Nicolas F.; Burk, Robert D.] Univ Med & Dent New Jersey, New Jersey Dent Sch, Dept Epidemiol & Populat Hlth, Newark, NJ 07103 USA.
[Fatahzadeh, Mahnaz] Univ Med & Dent New Jersey, New Jersey Dent Sch, Dept Diagnost Sci, Newark, NJ 07103 USA.
[Herrero, Rolando] Fdn INCIENSA, San Jose, Costa Rica.
[Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Burk, RD (reprint author), Albert Einstein Coll Med, Albert Einstein Canc Ctr, 1300 Morris Pk Ave, Bronx, NY 10461 USA.
EM robert.burk@einstein.yu.edu
RI Sun, Chang/I-6326-2012; Chen, Zigui/E-8490-2017
FU National Cancer Institute [CA78527, P30CA013330]; National Institutes of
Health [AI-51519]
FX This work was supported by the National Cancer Institute (grant CA78527
to R. D. B.); the Einstein-Montefiore Center for AIDS, funded by the
National Institutes of Health (grant AI-51519); and the Einstein Cancer
Research Center, funded by the National Cancer Institute (grant
P30CA013330).
NR 30
TC 68
Z9 68
U1 1
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD SEP 1
PY 2011
VL 204
IS 5
BP 787
EP 792
DI 10.1093/infdis/jir383
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 809QB
UT WOS:000294070700017
PM 21844305
ER
PT J
AU Thu, KL
Pikor, LA
Chari, R
Wilson, IM
MacAulay, CE
English, JC
Tsao, MS
Gazdar, AF
Lam, S
Lam, WL
Lockwood, WW
AF Thu, Kelsie L.
Pikor, Larissa A.
Chari, Raj
Wilson, Ian M.
MacAulay, Calum E.
English, John C.
Tsao, Ming-Sound
Gazdar, Adi F.
Lam, Stephen
Lam, Wan L.
Lockwood, William W.
TI Genetic Disruption of KEAP1/CUL3 E3 Ubiquitin Ligase Complex Components
is a Key Mechanism of NF-KappaB Pathway Activation in Lung Cancer
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Article
DE KEAP1; CUL3; RBX1; IKBKB; NF-kappa B signaling; Genetic disruption
ID OXIDATIVE STRESS; CELL-LINES; HUMAN GENOME; NRF2; REQUIREMENT;
MUTATIONS; CATALOG; TARGETS; PROTEIN; ADAPTER
AB Introduction: Inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta (IKBKB) (IKK-beta/IKK-2), which activates NF-kappa B, is a substrate of the KEAP1-CUL3-RBX1 E3-ubiquitin ligase complex, implicating this complex in NF-kappa B pathway regulation. We investigated complex component gene disruption as a novel genetic mechanism of NF-kappa B activation in non-small cell lung cancer.
Methods: A total of 644 tumor-and 90 cell-line genomes were analyzed for gene dosage status of the individual complex components and IKBKB. Gene expression of these genes and NF-kappa B target genes were analyzed in 48 tumors. IKBKB protein levels were assessed in tumors with and without complex or IKBKB genetic disruption. Complex component knockdown was performed to assess effects of the E3-ligase complex on IKBKB and NF-kappa B levels, and phenotypic importance of IKBKB expression was measured by pharmacological inhibition.
Results: We observed strikingly frequent genetic disruption (42%) and aberrant expression (63%) of the E3-ligase complex and IKBKB in the samples examined. Although both adenocarcinomas and squamous cell carcinomas showed complex disruption, the patterns of gene disruption differed. IKBKB levels were elevated with complex disruption, knockdown of complex components increased activated forms of IKBKB and NF-kappa B proteins, and IKBKB inhibition detriments cell viability, highlighting the biological significance of complex disruption. NF-kappa B target genes were overex-pressed in samples with complex disruption, further demonstrating the effect of complex disruption on NF-kappa B activity.
Conclusions: Gene dosage alteration is a prominent mechanism that disrupts each component of the KEAP1-CUL3-RBX1 complex and its NF-kappa B stimulating substrate, IKBKB. Herein, we show that, multiple component disruption of this complex represents a novel mechanism of NF-kappa B activation in non-small cell lung cancer.
C1 [Thu, Kelsie L.; Pikor, Larissa A.; Chari, Raj; Wilson, Ian M.; MacAulay, Calum E.; Lam, Stephen; Lam, Wan L.; Lockwood, William W.] BC Canc Res Ctr, Integrat Oncol Dept, Vancouver, BC V5Z 1L3, Canada.
[English, John C.] Vancouver Gen Hosp, Dept Pathol, Vancouver, BC V5Z 1M9, Canada.
[Tsao, Ming-Sound] Princess Margaret Hosp, Ontario Canc Inst, Univ Hlth Network, Toronto, ON M4X 1K9, Canada.
[Tsao, Ming-Sound] Univ Toronto, Toronto, ON, Canada.
[Gazdar, Adi F.] Univ Texas SW Med Ctr Dallas, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA.
[Lockwood, William W.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Thu, KL (reprint author), BC Canc Res Ctr, Integrat Oncol Dept, 675 W 10th Ave, Vancouver, BC V5Z 1L3, Canada.
EM kthu@bccrc.ca
RI MacAulay, Calum/K-1795-2016
FU Canadian Institutes for Health Research (CIHR) [MOP 86731, MOP 94867];
Canadian Cancer Society [CCS20485, CCS20527]; NCI Early Detection
Research Network (EDRN) [5U01, CA84971-10]; Canary Foundation; Michael
Smith Foundation for Health Research; Vanier Canada Graduate
Scholarship; University of British Columbia Interdisciplinary Oncology
Program
FX Supported by funds from the Canadian Institutes for Health Research
(CIHR; MOP 86731 and MOP 94867), Canadian Cancer Society (CCS20485 and
CCS20527), NCI Early Detection Research Network (EDRN; 5U01 CA84971-10),
and the Canary Foundation. K.L.T., L.A.P., R.C., I.M.W., and W.W.L. are
supported by scholarships from the CIHR, the Michael Smith Foundation
for Health Research, Vanier Canada Graduate Scholarship, and the
University of British Columbia Interdisciplinary Oncology Program.
NR 31
TC 26
Z9 27
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1556-0864
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD SEP
PY 2011
VL 6
IS 9
BP 1521
EP 1529
DI 10.1097/JTO.0b013e3182289479
PG 9
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 808VB
UT WOS:000294008000013
PM 21795997
ER
PT J
AU Thu, KL
Chari, R
Lockwood, WW
Lam, S
Lam, WL
AF Thu, Kelsie L.
Chari, Raj
Lockwood, William W.
Lam, Stephen
Lam, Wan L.
TI miR-101 DNA Copy Loss is a Prominent Subtype Specific Event in Lung
Cancer
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Article
DE Non-small cell lung cancer; miR-101; Deletion
ID GASTRIC-CANCER; GENOMIC LOSS; MICRORNA-101; EXPRESSION; CARCINOMA; EZH2
AB Introduction: MicroRNA-101 (miR-101) is frequently downregulated in cancer and exhibits antitumorigenic properties, suggesting that miR-101 is a putative tumor suppressor. miR-101 is encoded at two loci in the human genome: 1p31.3 (miR-101-1) and 9p24.1 (miR-101-2). We sought to investigate miR-101 locus-specific deletions and genomic loss in the major subtypes of lung cancer.
Methods: Analyses of high-resolution array comparative genomic hybridization and single-nucleotide polymorphism array data were performed to determine the DNA copy number status and deletion boundaries of miR-101-1 and miR-101-2 in seven independent cohorts that comprised 1236 lung cancer specimens and 20 lung carcinoma in situ samples. miR-101 expression was also investigated in lung cancer cell lines and tumors.
Results: miR-101 loss at either genomic locus was identified in 29% of lung cancers analyzed and was associated with reduced miR-101 expression. Loss was more frequent at the 9p locus and occurred more often in NSCLC as opposed to small cell lung cancer. Lung carcinoma in situ also harbored miR-101 deletions, suggesting that genomic loss may be an early event in lung cancer development. Finally, miR-101 deletions on 9p were exclusive of CDKN2A deletions in several cases, providing evidence that loss of miR-101 is not merely a passenger of CDKN2A deletion.
Conclusions: miR-101 genomic loss occurs frequently in NSCLC and may be an early event in lung tumorigenesis. DNA deletions likely represent a prominent molecular mechanism of miR-101 downregulation in NSCLC but not in small cell lung cancer.
C1 [Thu, Kelsie L.; Chari, Raj; Lockwood, William W.; Lam, Stephen; Lam, Wan L.] BC Canc Res Ctr, Vancouver, BC V5Z 1L3, Canada.
[Lockwood, William W.] NIH, Bethesda, MD 20892 USA.
RP Thu, KL (reprint author), BC Canc Res Ctr, 675 W 10th Ave, Vancouver, BC V5Z 1L3, Canada.
EM kthu@bccrc.ca
FU Michael Smith Foundation for Health Research; Vanier Canada Graduate
Scholarship; Canadian Institutes for Health Research (CIHR) [MOP 86731,
MOP 94867]; Canadian Cancer Society [CCS20485]; NCI Early Detection
Research Network (EDRN) [5U01 CA84971-10]; Canary Foundation
FX Thu, Chari, and Lockwood were supported by scholarships from the CIHR,
the Michael Smith Foundation for Health Research, and Vanier Canada
Graduate Scholarship.; Supported by the Canadian Institutes for Health
Research (CIHR; MOP 86731, MOP 94867), Canadian Cancer Society
(CCS20485), NCI Early Detection Research Network (EDRN; 5U01
CA84971-10), and the Canary Foundation.
NR 19
TC 16
Z9 21
U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1556-0864
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD SEP
PY 2011
VL 6
IS 9
BP 1594
EP 1598
DI 10.1097/JTO.0b013e3182217d81
PG 5
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 808VB
UT WOS:000294008000022
PM 21849855
ER
PT J
AU Crawford, ED
Hirst, K
Kusek, JW
Donnell, RF
Kaplan, SA
McVary, KT
Mynderse, LA
Roehrborn, CG
Smith, CP
Bruskewitz, R
AF Crawford, E. David
Hirst, Kathryn
Kusek, John W.
Donnell, Robert F.
Kaplan, Steven A.
McVary, Kevin T.
Mynderse, Lance A.
Roehrborn, Claus G.
Smith, Christopher P.
Bruskewitz, Reginald
TI Effects of 100 and 300 Units of Onabotulinum Toxin A on Lower Urinary
Tract Symptoms of Benign Prostatic Hyperplasia: A Phase II Randomized
Clinical Trial
SO JOURNAL OF UROLOGY
LA English
DT Article
DE prostatic hyperplasia; onabotulinum toxin A
ID BOTULINUM TOXIN; DETRUSOR OVERACTIVITY; INNERVATION; INJECTIONS; RELIEF
AB Purpose: We conducted a 2-stage, multicenter, double-blind, randomized phase II clinical trial of 100 and 300 unit doses of onabotulinum toxin A to treat the lower urinary tract symptoms of benign prostatic hyperplasia.
Materials and Methods: Men 50 years old or older with clinically diagnosed benign prostatic hyperplasia, American Urological Association symptom index 8 or greater, maximum urinary flow rate less than 15 ml per second, voided volume 125 ml or greater, and post-void residual 350 ml or less were randomized to prostatic transrectal injection of 100 or 300 units of onabotulinum toxin A. The primary outcome was at least 30% improvement from baseline to 3 months in American Urological Association symptom index and/or maximum urinary flow rate and safety. The men were followed for 12 months.
Results: A total of 134 men were randomized and treated (68 with 100 units, 66 with 300 units), with 131 assessed at 3 months and 108 assessed at 12 months. Each dose met the 3-month primary outcome criteria. In the 100 unit arm the mean baseline American Urological Association symptom index of 18.8 decreased by 7.1 and 6.9 at 3 and 12 months, respectively. In the 300 unit arm the baseline of 19.5 decreased by 8.9 and 7.1, respectively. In the 100 unit arm the mean baseline maximum urinary flow rate of 10.0 ml per second increased by 2.5 and 2.2, respectively, and in the 300 unit arm the baseline of 9.6 increased by 2.6 and 2.3, respectively.
Conclusions: The intraprostatic injection of 100 or 300 units of onabotulinum toxin A passed predetermined criteria for treatment efficacy and safety, and a randomized trial with either dose is warranted. The 100 unit dose may be preferable due to similar efficacy with reduced costs and adverse effects.
C1 [Hirst, Kathryn] George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA.
[Crawford, E. David] Univ Colorado Denver, Sect Urol Oncol, Sch Med, Aurora, CO USA.
[Kusek, John W.] NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD USA.
[Donnell, Robert F.] Med Coll Wisconsin, Dept Urol, Milwaukee, WI 53226 USA.
[Bruskewitz, Reginald] Univ Wisconsin, Dept Urol, Madison, WI USA.
[Kaplan, Steven A.] Cornell Univ, Dept Urol, New York, NY 10021 USA.
[McVary, Kevin T.] Northwestern Univ, Sch Med, Dept Urol, Chicago, IL 60611 USA.
[Mynderse, Lance A.] Mayo Clin, Dept Urol, Rochester, MN USA.
[Roehrborn, Claus G.] Univ Texas SW Med Ctr Dallas, Dept Urol, Dallas, TX 75390 USA.
[Smith, Christopher P.] Baylor Coll Med, Dept Urol, Houston, TX 77030 USA.
RP Hirst, K (reprint author), George Washington Univ, Ctr Biostat, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA.
EM khirst@bsc.gwu.edu
FU NIDDK/NIH [U01 DK60791, U01 DK60795, U01 DK60799, U01 DK60803, U01
DK60804, U01 DK060810, U01 DK60813, U01 DK60817]
FX Supported by NIDDK/NIH Grants U01 DK60791 (University of Colorado
Denver), U01 DK60795 (Northwestern University), U01 DK60799 (University
of Texas Southwestern Medical Center), U01 DK60803 (Medical College of
Wisconsin), U01 DK60804 (Cornell University), U01 DK060810 (Baylor
College of Medicine), U01 DK60813 (Mayo Clinic) and U01 DK60817 (George
Washington University).
NR 18
TC 26
Z9 26
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
J9 J UROLOGY
JI J. Urol.
PD SEP
PY 2011
VL 186
IS 3
BP 965
EP 970
DI 10.1016/j.juro.2011.04.062
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA 804XL
UT WOS:000293688300062
PM 21791356
ER
PT J
AU Yang, HP
Walmer, DK
Merisier, D
Gage, JC
Bell, L
Rangwala, S
Shrestha, N
Kobayashi, L
Eder, PS
Castle, PE
AF Yang, Hannah P.
Walmer, David K.
Merisier, Delson
Gage, Julia C.
Bell, Laura
Rangwala, Sameera
Shrestha, Niwashin
Kobayashi, Lori
Eder, Paul S.
Castle, Philip E.
TI A pilot analytic study of a research-level, lower-cost human
papillomavirus 16, 18, and 45 test
SO JOURNAL OF VIROLOGICAL METHODS
LA English
DT Article
DE Human papillomavirus (HPV); HPV test; Cervical cancer; HPV genotypes
ID CERVICAL-CANCER; WOMEN; RISK; DNA; PREVALENCE; PRIMERS; PCR
AB The analytic performance of a low-cost, research-stage DNA test for the most carcinogenic human papillomavirus (HPV) genotypes (HPV16. HPV18. and HPV45) in aggregate was evaluated among carcinogenic HPV-positive women, which might be used to decide who needs immediate colposcopy in low-resource settings ("triage test"). We found that HPV16/18/45 test agreed well with two DNA tests, a GP5+/6+ genotyping assay (Kappa = 0.77) and a quantitative PCR assay (at a cutpoint of 5000 viral copies) (Kappa = 0.87). DNA sequencing on a subset of 16 HPV16/18/45 positive and 16 HPV16/18/45 negative verified the analytic specificity of the research test. It is concluded that the HPV16/18/45 assay is a promising triage test with a minimum detection of approximately 5000 viral copies, the clinically relevant threshold. Published by Elsevier B.V.
C1 [Yang, Hannah P.; Gage, Julia C.] Natl Canc Inst, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Walmer, David K.; Merisier, Delson] Family Hlth Minist, Durham, NC 27705 USA.
[Walmer, David K.; Merisier, Delson] Duke Univ, Duke Global Hlth Inst, Durham, NC 27710 USA.
[Bell, Laura; Rangwala, Sameera; Shrestha, Niwashin; Kobayashi, Lori; Eder, Paul S.] QIAGEN Inc, Gaithersburg, MD 20878 USA.
[Castle, Philip E.] Amer Soc Clin Pathol Inst, Washington, DC 20005 USA.
RP Yang, HP (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Room 5102,MSC 7234, Bethesda, MD 20892 USA.
EM yanghan@mail.nih.gov
FU NIH/NCI
FX The evaluation of the HPV16/18/45 triage test data was conducted for
research purposes and was supported in part by the intramural research
program of the NIH/NCI. The authors would like to recognize Adam
Mallonee of QIAGEN for his contribution to performing the genotyping
tests.
NR 19
TC 4
Z9 4
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-0934
J9 J VIROL METHODS
JI J. Virol. Methods
PD SEP
PY 2011
VL 176
IS 1-2
BP 112
EP 114
DI 10.1016/j.jviromet.2011.05.024
PG 3
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Virology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Virology
GA 809ED
UT WOS:000294033700017
PM 21640138
ER
PT J
AU Radoshitzky, SR
Warfield, KL
Chi, XL
Dong, L
Kota, K
Bradfute, SB
Gearhart, JD
Retterer, C
Kranzusch, PJ
Misasi, JN
Hogenbirk, MA
Wahl-Jensen, V
Volchkov, VE
Cunningham, JM
Jahrling, PB
Aman, MJ
Bavari, S
Farzan, M
Kuhn, JH
AF Radoshitzky, Sheli R.
Warfield, Kelly L.
Chi, Xiaoli
Dong, Lian
Kota, Krishna
Bradfute, Steven B.
Gearhart, Jacqueline D.
Retterer, Cary
Kranzusch, Philip J.
Misasi, John N.
Hogenbirk, Marc A.
Wahl-Jensen, Victoria
Volchkov, Viktor E.
Cunningham, James M.
Jahrling, Peter B.
Aman, M. Javad
Bavari, Sina
Farzan, Michael
Kuhn, Jens H.
TI Ebolavirus Delta-Peptide Immunoadhesins Inhibit Marburgvirus and
Ebolavirus Cell Entry
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID ANGIOTENSIN-CONVERTING ENZYME-2; SMALL GLYCOPROTEIN SGP; VIRUS
GLYCOPROTEIN; ENDOSOMAL CATHEPSINS; ELECTRON-MICROSCOPY; SARS
CORONAVIRUS; VIRAL ENTRY; RECEPTOR; SEQUENCE; MEMBRANE
AB With the exception of Reston and Lloviu viruses, filoviruses (marburgviruses, ebolaviruses, and "cuevaviruses") cause severe viral hemorrhagic fevers in humans. Filoviruses use a class I fusion protein, GP(1,2), to bind to an unknown, but shared, cell surface receptor to initiate virus-cell fusion. In addition to GP(1,2), ebolaviruses and cuevaviruses, but not marburgviruses, express two secreted glycoproteins, soluble GP (sGP) and small soluble GP (ssGP). All three glycoproteins have identical N termini that include the receptor-binding region (RBR) but differ in their C termini. We evaluated the effect of the secreted ebolavirus glycoproteins on marburgvirus and ebolavirus cell entry, using Fc-tagged recombinant proteins. Neither sGP-Fc nor ssGP-Fc bound to filovirus-permissive cells or inhibited GP(1,2)-mediated cell entry of pseudotyped retroviruses. Surprisingly, several Fc-tagged Delta-peptides, which are small C-terminal cleavage products of sGP secreted by ebolavirus-infected cells, inhibited entry of retroviruses pseudotyped with Marburg virus GP(1,2), as well as Marburg virus and Ebola virus infection in a dose-dependent manner and at low molarity despite absence of sequence similarity to filovirus RBRs. Fc-tagged Delta-peptides from three ebolaviruses (Ebola virus, Sudan virus, and Ta Forest virus) inhibited GP(1,2)-mediated entry and infection of viruses comparably to or better than the Fc-tagged RBRs, whereas the Delta-peptide-Fc of an ebolavirus nonpathogenic for humans (Reston virus) and that of an ebolavirus with lower lethality for humans (Bundibugyo virus) had little effect. These data indicate that Delta-peptides are functional components of ebolavirus proteomes. They join cathepsins and integrins as novel modulators of filovirus cell entry, might play important roles in pathogenesis, and could be exploited for the synthesis of powerful new antivirals.
C1 [Wahl-Jensen, Victoria; Jahrling, Peter B.; Kuhn, Jens H.] NIAID, Integrated Res Facil Ft Detrick, NIH, Frederick, MD 21702 USA.
[Radoshitzky, Sheli R.; Warfield, Kelly L.; Chi, Xiaoli; Dong, Lian; Kota, Krishna; Bradfute, Steven B.; Gearhart, Jacqueline D.; Retterer, Cary; Aman, M. Javad; Bavari, Sina] USA, Med Res Inst Infect Dis, Frederick, MD 21702 USA.
[Radoshitzky, Sheli R.; Kranzusch, Philip J.; Hogenbirk, Marc A.; Farzan, Michael; Kuhn, Jens H.] Harvard Univ, New England Primate Res Ctr, Sch Med, Southborough, MA 01772 USA.
[Warfield, Kelly L.; Aman, M. Javad] Integrated BioTherapeut Inc, Germantown, MD 20876 USA.
[Misasi, John N.; Cunningham, James M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Hogenbirk, Marc A.] Univ Utrecht, Eijkman Grad Sch Immunol & Infect Dis, NL-3508 TC Utrecht, Netherlands.
[Volchkov, Viktor E.] Univ Lyon 1, Ecole Normale Super Lyon, INSERM, U758, F-69365 Lyon, France.
[Kuhn, Jens H.] Free Univ Berlin, Dept Biol, D-14195 Berlin, Germany.
RP Kuhn, JH (reprint author), NIAID, Integrated Res Facil Ft Detrick, NIH, B-8200 Res Plaza, Frederick, MD 21702 USA.
EM kuhnjens@mail.nih.gov
RI Kuhn, Jens H./B-7615-2011; Volchkov, Viktor/M-7846-2014
OI Kuhn, Jens H./0000-0002-7800-6045; Volchkov, Viktor/0000-0001-7896-8706
FU NIAID [HHSN272200200016I]; NERCE/BEID, Boston, MA [AI057159]; Agence
Nationale de la Recherche [ANR-07-MIME-006-01]
FX J.H.K. and V.W.-J. performed part of this work as employees of Tunnell
Consulting, Inc., a subcontractor to Battelle Memorial Institute, under
its prime contract with NIAID (contract HHSN272200200016I). NERCE/BEID,
Boston, MA, provided a Career Development Fellowship to J.H.K. (grant
AI057159). Agence Nationale de la Recherche supported V. E. V.
(ANR-07-MIME-006-01).
NR 60
TC 22
Z9 25
U1 0
U2 15
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 2011
VL 85
IS 17
BP 8502
EP 8513
DI 10.1128/JVI.02600-10
PG 12
WC Virology
SC Virology
GA 804AO
UT WOS:000293626100005
PM 21697477
ER
PT J
AU Pak, V
Heidecker, G
Pathak, VK
Derse, D
AF Pak, Vladimir
Heidecker, Gisela
Pathak, Vinay K.
Derse, David
TI The Role of Amino-Terminal Sequences in Cellular Localization and
Antiviral Activity of APOBEC3B
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID LEUKEMIA-VIRUS TYPE-1; CYTIDINE DEAMINASE DOMAINS; ANTIRETROVIRAL
FACTOR; POTENT INHIBITORS; HIV-1 VIF; DNA; RNA; RETROTRANSPOSITION;
RESTRICTION; PROTEINS
AB Human APOBEC3B (A3B) has been described as a potent inhibitor of retroviral infection and retrotransposition. However, we found that the predominantly nuclear A3B only weakly restricted infection by HIV-1, HIV-1 Delta vif, and human T-cell leukemia virus type 1 (HTLV-1), while significantly inhibiting LINE-1 retrotransposition. The chimeric construct A3G/B, in which the first 60 amino acids of A3B were replaced with those of A3G, restricted HIV-1, HIV-1 Delta vif, and HTLV-1 infection, as well as LINE-1 retrotransposition. In contrast to the exclusively cytoplasmic A3G, which is inactive against LINE-1 retrotransposition, the A3G/B protein, while localized mainly to the cytoplasm, was also present in the nucleus. Further mutational analysis revealed that residues 18, 19, 22, and 24 in A3B were the major determinants for nuclear versus cytoplasmic localization and antiretroviral activity. HIV-1 Delta vif packages A3G, A3B, and A3G/B into particles with close-to-equal efficiencies. Mutation E68Q or E255Q in the active centers of A3G/B resulted in loss of the inhibitory activity against HIV-1 Delta vif, while not affecting activity against LINE-1 retrotransposition. The low inhibition of HIV-1 Delta vif by A3B correlated with a low rate of G-to-A hypermutation. In contrast, viruses that had been exposed to A3G/B showed a high number of G-to-A transitions. The mutation pattern was similar to that previously reported for A3B, with a preference for the GA context. In summary, these observations suggest that changing 4 residues in the amino terminus of A3B not only retargets the protein from the nucleus to the cytoplasm but also enhances its ability to restrict HIV while retaining inhibition of retrotransposition.
C1 [Pak, Vladimir; Heidecker, Gisela; Pathak, Vinay K.; Derse, David] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.
RP Heidecker, G (reprint author), NCI, HIV Drug Resistance Program, POB B,Bldg 535,Rm 111, Frederick, MD 21702 USA.
EM heidecke@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 48
TC 19
Z9 20
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD SEP
PY 2011
VL 85
IS 17
BP 8538
EP 8547
DI 10.1128/JVI.02645-10
PG 10
WC Virology
SC Virology
GA 804AO
UT WOS:000293626100008
PM 21715505
ER
PT J
AU Kim, SH
Subbiah, M
Samuel, AS
Collins, PL
Samal, SK
AF Kim, Shin-Hee
Subbiah, Madhuri
Samuel, Arthur S.
Collins, Peter L.
Samal, Siba K.
TI Roles of the Fusion and Hemagglutinin-Neuraminidase Proteins in
Replication, Tropism, and Pathogenicity of Avian Paramyxoviruses
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID NEWCASTLE-DISEASE VIRUS; COMPLETE GENOME SEQUENCE; RESPIRATORY SYNCYTIAL
VIRUS; CELL-FUSION; HN PROTEIN; MUTATIONAL ANALYSIS; CLEAVAGE SITE;
FOREIGN GENE; CLONED CDNA; F-PROTEIN
AB Virulent and moderately virulent strains of Newcastle disease virus (NDV), representing avian paramyxovirus serotype 1 (APMV-1), cause respiratory and neurological disease in chickens and other species of birds. In contrast, APMV-2 is avirulent in chickens. We investigated the role of the fusion (F) and hemagglutinin-neuraminidase (HN) envelope glycoproteins in these contrasting phenotypes by designing chimeric viruses in which the F and HN glycoproteins or their ectodomains were exchanged individually or together between the moderately virulent, neurotropic NDV strain Beaudette C (BC) and the avirulent APMV-2 strain Yucaipa. When we attempted to exchange the complete F and HN glycoproteins individually and together between the two viruses, the only construct that could be recovered was recombinant APMV-2 strain Yucaipa (rAPMV-2), containing the NDV F glycoprotein in place of its own. This substitution of NDV F into APMV-2 was sufficient to confer the neurotropic, neuroinvasive, and neurovirulent phenotypes, in spite of all being at reduced levels compared to what was seen for NDV-BC. When the ectodomains of F and HN were exchanged individually and together, two constructs could be recovered: NDV, containing both the F and HN ectodomains of APMV-2; and APMV-2, containing both ectodomains of NDV. This supported the idea that homologous cytoplasmic tails and matched F and HN ectodomains are important for virus replication. Analysis of these viruses for replication in vitro, syncytium formation, mean embryo death time, intracerebral pathogenicity index, and replication and tropism in 1-day-old chicks and 2-week-old chickens showed that the two contrasting phenotypes of NDV and APMV-2 could largely be transferred between the two backbones by transfer of homotypic F and HN ectodomains. Further analysis provided evidence that the homologous stalk domain of NDV HN is essential for virus replication, while the globular head domain of NDV HN could be replaced with that of APMV-2 with only a minimal attenuating effect. These results demonstrate that the F and HN ectodomains together determine the cell fusion, tropism, and virulence phenotypes of NDV and APMV-2 and that the regions of HN that are critical to replication and the species-specific phenotypes include the cytoplasmic tail and stalk domain but not the globular head domain.
C1 [Kim, Shin-Hee; Subbiah, Madhuri; Samuel, Arthur S.; Samal, Siba K.] Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
[Collins, Peter L.] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA.
RP Samal, SK (reprint author), Univ Maryland, Virginia Maryland Reg Coll Vet Med, 8075 Greenmead Dr, College Pk, MD 20742 USA.
EM ssamal@umd.edu
FU National Institute of Allergy and Infectious Diseases (NIAID)
[N01A060009]; NIAID, National Institutes of Health (NIH)
FX This research was supported by National Institute of Allergy and
Infectious Diseases (NIAID) contract no. N01A060009 (85% support) and
NIAID, National Institutes of Health (NIH) Intramural Research Program
(15% support).
NR 57
TC 19
Z9 23
U1 1
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD SEP
PY 2011
VL 85
IS 17
BP 8582
EP 8596
DI 10.1128/JVI.00652-11
PG 15
WC Virology
SC Virology
GA 804AO
UT WOS:000293626100012
PM 21680512
ER
PT J
AU Boon, D
Mahar, JE
Abente, EJ
Kirkwood, CD
Purcell, RH
Kapikian, AZ
Green, KY
Bok, K
AF Boon, Denali
Mahar, Jackie E.
Abente, Eugenio J.
Kirkwood, Carl D.
Purcell, Robert H.
Kapikian, Albert Z.
Green, Kim Y.
Bok, Karin
TI Comparative Evolution of GII.3 and GII.4 Norovirus over a 31-Year Period
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID LINKED IMMUNOSORBENT ASSAYS; AUTOMATED PROTEIN-STRUCTURE; I-TASSER;
ACUTE GASTROENTERITIS; STRUCTURE PREDICTION; HUMAN-POPULATIONS;
SEQUENCE-ANALYSIS; NORWALK VIRUS; P2 DOMAIN; INFECTION
AB Noroviruses are the most common cause of epidemic gastroenteritis. Genotype II.3 is one of the most frequently detected noroviruses associated with sporadic infections. We studied the evolution of the major capsid gene from seven archival GII.3 noroviruses collected during a cross-sectional study at the Children's Hospital in Washington, DC, from 1975 through 1991, together with capsid sequence from 56 strains available in GenBank. Evolutionary analysis concluded that GII.3 viruses evolved at a rate of 4.16 x 10(-3) nucleotide substitutions/site/year (strict clock), which is similar to that described for the more prevalent GII.4 noroviruses. The analysis of the amino acid changes over the 31-year period found that GII.3 viruses evolve at a relatively steady state, maintaining 4% distance, and have a tendency to revert back to previously used residues while preserving the same carbohydrate binding profile. In contrast, GII.4 viruses demonstrate increasing rates of distance over time because of the continued integration of new amino acids and changing HBGA binding patterns. In GII.3 strains, seven sites acting under positive selection were predicted to be surface-exposed residues in the P2 domain, in contrast to GII.4 positively selected sites located primarily in the shell domain. Our study suggests that GII.3 noroviruses caused disease as early as 1975 and that they evolve via a specific pattern, responding to selective pressures induced by the host rather than presenting a nucleotide evolution rate lower than that of GII.4 noroviruses, as previously proposed. Understanding the evolutionary dynamics of prevalent noroviruses is relevant to the development of effective prevention and control strategies.
C1 [Bok, Karin] NIAID, Caliciviruses Sect, Infect Dis Lab, NIH,DHHS, Bethesda, MD 20892 USA.
[Mahar, Jackie E.; Kirkwood, Carl D.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic, Australia.
[Mahar, Jackie E.] La Trobe Univ, Bundoora, Vic 3086, Australia.
RP Bok, K (reprint author), NIAID, Caliciviruses Sect, Infect Dis Lab, NIH,DHHS, 50 South Dr,Bldg 50,Room 6316, Bethesda, MD 20892 USA.
EM bokk@niaid.nih.gov
OI Abente, Eugenio/0000-0002-3390-2786
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases.
NR 48
TC 56
Z9 58
U1 0
U2 3
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 2011
VL 85
IS 17
BP 8656
EP 8666
DI 10.1128/JVI.00472-11
PG 11
WC Virology
SC Virology
GA 804AO
UT WOS:000293626100019
PM 21715504
ER
PT J
AU Vinton, C
Klatt, NR
Harris, LD
Briant, JA
Sanders-Beer, BE
Herbert, R
Woodward, R
Silvestri, G
Pandrea, I
Apetrei, C
Hirsch, VM
Brenchley, JM
AF Vinton, Carol
Klatt, Nichole R.
Harris, Levelle D.
Briant, Judith A.
Sanders-Beer, Brigitte E.
Herbert, Richard
Woodward, Ruth
Silvestri, Guido
Pandrea, Ivona
Apetrei, Cristian
Hirsch, Vanessa M.
Brenchley, Jason M.
TI CD4-Like Immunological Function by CD4(-) T Cells in Multiple Natural
Hosts of Simian Immunodeficiency Virus
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID SOOTY MANGABEYS; SIVAGM INFECTION; AIDS; PATTERNS; SUBSETS; HISTORY;
WILD
AB Many species of African nonhuman primates are natural hosts for individual strains of simian immunodeficiency virus (SIV). These infected animals do not, however, develop AIDS. Here we show that multiple species of African nonhuman primate species characteristically have low frequencies of CD4(+) T cells and high frequencies of both T cells that express only the alpha-chain of CD8 and double-negative T cells. These subsets of T cells are capable of eliciting functions generally associated with CD4(+) T cells, yet these cells lack surface expression of the CD4 protein and are, therefore, poor targets for SIV in vivo. These data demonstrate that coevolution with SIV has, in several cases, involved downregulation of receptors for the virus by otherwise-susceptible host target cells. Understanding the genetic factors that lead to downregulation of these receptors may lead to therapeutic interventions that mimic this modulation in progressive infections.
C1 [Vinton, Carol; Klatt, Nichole R.; Harris, Levelle D.; Briant, Judith A.; Hirsch, Vanessa M.; Brenchley, Jason M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Sanders-Beer, Brigitte E.] Bioqual, Rockville, MD 20850 USA.
[Herbert, Richard] NIAID, Expt Primate Virol Sect, NIH, Bethesda, MD 20892 USA.
[Woodward, Ruth] NICHD, NIH, Bethesda, MD 20892 USA.
[Silvestri, Guido] Emory Univ, Div Microbiol & Immunol, Atlanta, GA 30322 USA.
[Pandrea, Ivona; Apetrei, Cristian] Univ Pittsburgh, Ctr Vaccine Res, Pittsburgh, PA 15261 USA.
RP Brenchley, JM (reprint author), NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
EM jbrenchl@mail.nih.gov
OI Anesi, Judith/0000-0001-6671-4557
FU NIAID, NIH; Tulane National Primate Research Center [R01 AI064066, R01
AI065325, R01 AI66998, RR-00168]
FX These studies were supported by the intramural NIAID, NIH program and by
R01 AI064066 (I. P.), R01 AI065325 (C. A.), R01 AI66998 (G. S.), and
RR-00168 (Tulane National Primate Research Center).
NR 30
TC 28
Z9 28
U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD SEP
PY 2011
VL 85
IS 17
BP 8702
EP 8708
DI 10.1128/JVI.00332-11
PG 7
WC Virology
SC Virology
GA 804AO
UT WOS:000293626100023
PM 21715501
ER
PT J
AU Li, YX
O'Dell, S
Walker, LM
Wu, XL
Guenaga, J
Feng, Y
Schmidt, SD
McKee, K
Louder, MK
Ledgerwood, JE
Graham, BS
Haynes, BF
Burton, DR
Wyatt, RT
Mascola, JR
AF Li, Yuxing
O'Dell, Sijy
Walker, Laura M.
Wu, Xueling
Guenaga, Javier
Feng, Yu
Schmidt, Stephen D.
McKee, Krisha
Louder, Mark K.
Ledgerwood, Julie E.
Graham, Barney S.
Haynes, Barton F.
Burton, Dennis R.
Wyatt, Richard T.
Mascola, John R.
TI Mechanism of Neutralization by the Broadly Neutralizing HIV-1 Monoclonal
Antibody VRC01
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; PROXIMAL EXTERNAL REGION; ENVELOPE
GLYCOPROTEIN; SOLUBLE CD4; OLIGOMERIC STRUCTURE; T4 MOLECULE; GP120;
GP41; RECEPTOR; BINDING
AB The structure of VRC01 in complex with the HIV-1 gp120 core reveals that this broadly neutralizing CD4 binding site (CD4bs) antibody partially mimics the interaction of the primary virus receptor, CD4, with gp120. Here, we extended the investigation of the VRC01-gp120 core interaction to the biologically relevant viral spike to better understand the mechanism of VRC01-mediated neutralization and to define viral elements associated with neutralization resistance. In contrast to the interaction of CD4 or the CD4bs monoclonal antibody (MAb) b12 with the HIV-1 envelope glycoprotein (Env), occlusion of the VRC01 epitope by quaternary constraints was not a major factor limiting neutralization. Mutagenesis studies indicated that VRC01 contacts within the gp120 loop D, the CD4 binding loop, and the V5 region were necessary for optimal VRC01 neutralization, as suggested by the crystal structure. In contrast to interactions with the soluble gp120 monomer, VRC01 interaction with the native viral spike did not occur in a CD4-like manner; VRC01 did not induce gp120 shedding from the Env spike or enhance gp41 membrane proximal external region (MPER)-directed antibody binding to the Env spike. Finally, VRC01 did not display significant reactivity with human antigens, boding well for potential in vivo applications. The data indicate that VRC01 interacts with gp120 in the context of the functional spike in a manner distinct from that of CD4. It achieves potent neutralization by precisely targeting the CD4bs without requiring alterations of Env spike configuration and by avoiding steric constraints imposed by the quaternary structure of the functional Env spike.
C1 [Li, Yuxing; O'Dell, Sijy; Wu, Xueling; Schmidt, Stephen D.; McKee, Krisha; Louder, Mark K.; Ledgerwood, Julie E.; Graham, Barney S.; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Walker, Laura M.; Guenaga, Javier; Feng, Yu; Burton, Dennis R.; Wyatt, Richard T.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr TSRI, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Haynes, Barton F.] Duke Univ, Med Ctr, Durham, NC 27710 USA.
RP Mascola, JR (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA.
EM wyatt@scripps.edu; jmascola@nih.gov
RI Feng, Yu/A-3396-2012; Schmidt, Stephen/B-5398-2012
FU Vaccine Research Center, National Institute of Allergy and Infectious
Diseases, National Institutes of Health; International AIDS Vaccine
Initiative
FX This study was supported by the Intramural Research Program of the
Vaccine Research Center, National Institute of Allergy and Infectious
Diseases, National Institutes of Health, and the International AIDS
Vaccine Initiative.
NR 76
TC 107
Z9 108
U1 0
U2 19
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 2011
VL 85
IS 17
BP 8954
EP 8967
DI 10.1128/JVI.00754-11
PG 14
WC Virology
SC Virology
GA 804AO
UT WOS:000293626100046
PM 21715490
ER
PT J
AU Sakakibara, N
Mitra, R
McBride, AA
AF Sakakibara, Nozomi
Mitra, Ruchira
McBride, Alison A.
TI The Papillomavirus E1 Helicase Activates a Cellular DNA Damage Response
in Viral Replication Foci
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID TYPE-16 E7 ONCOPROTEIN; LARGE T-ANTIGEN; BOVINE PAPILLOMAVIRUS; IN-VIVO;
E2 PROTEIN; GENOME INTEGRITY; GROWTH ARREST; S-PHASE; PHOSPHORYLATION;
CHECKPOINT
AB The papillomavirus E1 and E2 proteins are essential for viral genome replication. E1 is a helicase that unwinds the viral origin and recruits host cellular factors to replicate the viral genome. E2 is a transcriptional regulator that helps recruit the E1 helicase to the origin and also plays a role in genome partitioning. We find that when coexpressed, the E1 and E2 proteins from several papillomavirus types localize to defined nuclear foci and result in growth suppression of the host cells. Growth suppression was due primarily to E1 protein function, and nuclear expression of E1 was accompanied by activation of a DNA damage response, resulting in phosphorylation of ATM, Chk2, and H2AX. Growth suppression and ATM activation required the ATPase and origin-specific binding functions of the E1 protein and resulted in active DNA repair, as evidenced by incorporation of nucleotide analogs and detection of free DNA ends. In the presence of the E2 protein, these activities became localized to nuclear foci. We postulate that these foci represent viral replication factories and that a cellular DNA damage response is activated to facilitate replication of viral DNA.
C1 [Sakakibara, Nozomi; Mitra, Ruchira; McBride, Alison A.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP McBride, AA (reprint author), NIAID, Viral Dis Lab, NIH, 4 Ctr Dr,MSC 0455, 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 51
TC 69
Z9 70
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD SEP
PY 2011
VL 85
IS 17
BP 8981
EP 8995
DI 10.1128/JVI.00541-11
PG 15
WC Virology
SC Virology
GA 804AO
UT WOS:000293626100048
PM 21734054
ER
PT J
AU Alexandre, KB
Gray, ES
Pantophlet, R
Moore, PL
McMahon, JB
Chakauya, E
O'Keefe, BR
Chikwamba, R
Morris, L
AF Alexandre, Kabamba Bankoledi
Gray, Elin S.
Pantophlet, Ralph
Moore, Penny L.
McMahon, James B.
Chakauya, Ereck
O'Keefe, Barry R.
Chikwamba, Rachel
Morris, Lynn
TI Binding of the Mannose-Specific Lectin, Griffithsin, to HIV-1 gp120
Exposes the CD4-Binding Site
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODIES; N-LINKED
GLYCOSYLATION; ENVELOPE GLYCOPROTEIN GP120; ENTRY INHIBITOR GRIFFITHSIN;
SUBTYPE-C; CD4 BINDING; TYPE-1 HIV-1; IN-VITRO; NEUTRALIZING ANTIBODIES
AB The glycans on HIV-1 gp120 play an important role in shielding neutralization-sensitive epitopes from antibody recognition. They also serve as targets for lectins that bind mannose-rich glycans. In this study, we investigated the interaction of the lectin griffithsin (GRFT) with HIV-1 gp120 and its effects on exposure of the CD4-binding site (CD4bs). We found that GRFT enhanced the binding of HIV-1 to plates coated with anti-CD4bs antibodies b12 and b6 or the CD4 receptor mimetic CD4-IgG2. The average enhancement of b12 or b6 binding was higher for subtype B viruses than for subtype C, while for CD4-IgG2, it was similar for both subtypes, although lower than observed with antibodies. This GRFT-mediated enhancement of HIV-1 binding to b12 was reflected in synergistic neutralization for 2 of the 4 viruses tested. The glycan at position 386, which shields the CD4bs, was involved in both GRFT-mediated enhancement of binding and neutralization synergism between GRFT and b12. Although GRFT enhanced CD4bs exposure, it simultaneously inhibited ligand binding to the coreceptor binding site, suggesting that GRFT-dependent enhancement and neutralization utilize independent mechanisms. This study shows for the first time that GRFT interaction with gp120 exposes the CD4bs through binding the glycan at position 386, which may have implications for how to access this conserved site.
C1 [Alexandre, Kabamba Bankoledi; Gray, Elin S.; Moore, Penny L.; Morris, Lynn] Natl Inst Communicable Dis, AIDS Virus Res Unit, ZA-2131 Johannesburg, South Africa.
[Pantophlet, Ralph] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada.
[Pantophlet, Ralph] Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada.
[McMahon, James B.; O'Keefe, Barry R.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21701 USA.
[Chakauya, Ereck; Chikwamba, Rachel] Ctr Sci & Ind Res, Pretoria, South Africa.
RP Morris, L (reprint author), Natl Inst Communicable Dis, AIDS Virus Res Unit, Private Bag X4, ZA-2131 Johannesburg, South Africa.
EM lynnm@nicd.ac.za
OI Moore, Penny/0000-0001-8719-4028; Gray, Elin/0000-0002-8613-3570
FU NEPAD; South African AIDS Vaccine Initiative (SAAVI); Fogarty
International Center, NIH [D43TW00231]; NIH, National Cancer Institute,
Center for Cancer Research
FX This work was funded by a Biofisa grant from NEPAD, the South African
AIDS Vaccine Initiative (SAAVI), and a training fellowship to K. B. A.
from Columbia University-Southern African Fogarty AIDS International
Training and Research Programme (AITRP) funded by the Fogarty
International Center, NIH (AITRP grant D43TW00231). This research was
also supported by the Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research (B.R.O. and J.B.M.).
NR 67
TC 20
Z9 20
U1 4
U2 10
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD SEP
PY 2011
VL 85
IS 17
BP 9039
EP 9050
DI 10.1128/JVI.02675-10
PG 12
WC Virology
SC Virology
GA 804AO
UT WOS:000293626100053
PM 21697467
ER
PT J
AU Race, B
Meade-White, K
Miller, MW
Fox, KA
Chesebro, B
AF Race, Brent
Meade-White, Kimberly
Miller, Michael W.
Fox, Karen A.
Chesebro, Bruce
TI In Vivo Comparison of Chronic Wasting Disease Infectivity from Deer with
Variation at Prion Protein Residue 96
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CREUTZFELDT-JAKOB-DISEASE; WHITE-TAILED DEER; BOVINE SPONGIFORM
ENCEPHALOPATHY; TRANSGENIC MICE; INFLUENCE SUSCEPTIBILITY; ODOCOILEUS
SPP.; MULE DEER; SCRAPIE; VARIANT; ELK
AB Chronic wasting disease (CWD) is a prion disease of cervids that causes neurodegeneration and death. Susceptibility to prion infections, including CWD, can be dependent on the amino acid sequence of the host prion protein (PrP). Here, CWD agent obtained from a deer expressing the 96SS genotype, associated with partial resistance to CWD, was used to infect transgenic (tg) mice expressing either 96GG or 96SS deer PrP. Transgenic mice expressing 96GG deer PrP succumbed to this agent, but tg mice expressing 96SS deer PrP did not. Additional studies using inocula from 96GG deer showed no transmission to 96SS PrP mice and delayed disease in 96GS mice. Thus, 96S PrP played an inhibitory role in disease progression in tg mice.
C1 [Race, Brent] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Hamilton, MT 59840 USA.
[Miller, Michael W.; Fox, Karen A.] Colorado Div Wildlife, Ft Collins, CO 80526 USA.
RP Race, B (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA.
EM raceb@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases, Division of
Intramural Research
FX Funding for this work was provided by the National Institute of Allergy
and Infectious Diseases, Division of Intramural Research.
NR 28
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U1 0
U2 13
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD SEP
PY 2011
VL 85
IS 17
BP 9235
EP 9238
DI 10.1128/JVI.00790-11
PG 4
WC Virology
SC Virology
GA 804AO
UT WOS:000293626100072
PM 21697479
ER
PT J
AU Berger, CT
Frahm, N
Price, DA
Mothe, B
Ghebremichael, M
Hartman, KL
Henry, LM
Brenchley, JM
Ruff, LE
Venturi, V
Pereyra, F
Sidney, J
Sette, A
Douek, DC
Walker, BD
Kaufmann, DE
Brander, C
AF Berger, Christoph T.
Frahm, Nicole
Price, David A.
Mothe, Beatriz
Ghebremichael, Musie
Hartman, Kari L.
Henry, Leah M.
Brenchley, Jason M.
Ruff, Laura E.
Venturi, Vanessa
Pereyra, Florencia
Sidney, John
Sette, Alessandro
Douek, Daniel C.
Walker, Bruce D.
Kaufmann, Daniel E.
Brander, Christian
TI High-Functional-Avidity Cytotoxic T Lymphocyte Responses to
HLA-B-Restricted Gag-Derived Epitopes Associated with Relative HIV
Control
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; HEPATITIS-C
VIRUS; CELL RESPONSES; INFECTED-CELLS; VIRAL LOAD; SELECTION PRESSURE;
CONSERVED REGIONS; CROSS-RECOGNITION; PERIPHERAL-BLOOD
AB Virus-specific cytotoxic T lymphocytes (CTL) with high levels of functional avidity have been associated with viral clearance in hepatitis C virus infection and with enhanced antiviral protective immunity in animal models. However, the role of functional avidity as a determinant of HIV-specific CTL efficacy remains to be assessed. Here we measured the functional avidities of HIV-specific CTL responses targeting 20 different, optimally defined CTL epitopes restricted by 13 different HLA class I alleles in a cohort comprising 44 HIV controllers and 68 HIV noncontrollers. Responses restricted by HLA-B alleles and responses targeting epitopes located in HIV Gag exhibited significantly higher functional avidities than responses restricted by HLA-A or HLA-C molecules (P = 0.0003) or responses targeting epitopes outside Gag (P < 0.0001). The functional avidities of Gag-specific and HLA-B-restricted responses were higher in HIV controllers than in noncontrollers (P = 0.014 and P = 0.018) and were not restored in HIV noncontrollers initiating antiretroviral therapy. T-cell receptor (TCR) analyses revealed narrower TCR repertoires in higher-avidity CTL populations, which were dominated by public TCR sequences in HIV controllers. Together, these data link the presence of high-avidity Gag-specific and HLA-B-restricted CTL responses with viral suppression in vivo and provide new insights into the immune parameters that mediate spontaneous control of HIV infection.
C1 [Berger, Christoph T.; Ghebremichael, Musie; Hartman, Kari L.; Henry, Leah M.; Pereyra, Florencia; Walker, Bruce D.; Kaufmann, Daniel E.; Brander, Christian] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA.
[Berger, Christoph T.; Ghebremichael, Musie; Hartman, Kari L.; Henry, Leah M.; Pereyra, Florencia; Walker, Bruce D.; Kaufmann, Daniel E.; Brander, Christian] Harvard Univ, Boston, MA 02115 USA.
[Frahm, Nicole] Fred Hutchinson Canc Res Ctr, NIAID HIV Vaccine Trials Network HVTN, Seattle, WA 98104 USA.
[Price, David A.; Brenchley, Jason M.; Ruff, Laura E.; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Price, David A.] Cardiff Univ, Sch Med, Dept Infect Immun & Biochem, Cardiff, S Glam, Wales.
[Mothe, Beatriz] Univ Autonoma Badalona, Hosp Germans Trias & Pujol, Lluita Sida Fdn, Barcelona, Spain.
[Mothe, Beatriz; Brander, Christian] Hosp Badalona Germans Trias & Pujol, IrsiCaixa AIDS Res Inst HIVACAT, Barcelona, Spain.
[Ghebremichael, Musie] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Venturi, Vanessa] Univ New S Wales, Ctr Vasc Res, Computat Biol Grp, Kensington, NSW 2033, Australia.
[Sidney, John; Sette, Alessandro] La Jolla Inst Allergy & Immunol, La Jolla, CA USA.
[Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA.
[Brander, Christian] ICREA, Barcelona, Spain.
RP Brander, C (reprint author), Hosp Badalona Germans Trias & Pujol, Fdn IrsiCaixa HIVACAT, AIDS Res Inst, Ctra Canyet S-N, Barcelona 08916, Catalonia, Spain.
EM cbrander@irsicaixa.es
RI Price, David/C-7876-2013;
OI Price, David/0000-0001-9416-2737; Brander, Christian/0000-0002-0548-5778
FU National Institutes of Health [R01 067 077]; Spanish FIPSE [36-0737-09];
University of Basel, Basel, Switzerland; Janggen-Pohn Foundation,
Switzerland; FIS, Madrid, Spain [CM08/00020]
FX This work was funded by a National Institutes of Health grant to C. B.
and D. E. K. (R01 067 077) and in part by the Spanish FIPSE grant
36-0737-09. C. T. B. is supported by a research grant from the
University of Basel, Basel, Switzerland, and the Janggen-Pohn
Foundation, Switzerland. D. A. P. is a Medical Research Council (United
Kingdom) senior clinical fellow. B. M. holds a research fellowship grant
from the FIS (Rio Hortega; CM08/00020), Madrid, Spain. C. B. is a senior
ICREA research professor.
NR 87
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U1 0
U2 10
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD SEP
PY 2011
VL 85
IS 18
BP 9334
EP 9345
DI 10.1128/JVI.00460-11
PG 12
WC Virology
SC Virology
GA 808DM
UT WOS:000293956400008
PM 21752903
ER
PT J
AU Chen, WZ
Feng, Y
Gong, R
Zhu, ZY
Wang, YP
Zhao, Q
Dimitrov, DS
AF Chen, Weizao
Feng, Yang
Gong, Rui
Zhu, Zhongyu
Wang, Yanping
Zhao, Qi
Dimitrov, Dimiter S.
TI Engineered Single Human CD4 Domains as Potent HIV-1 Inhibitors and
Components of Vaccine Immunogens
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; AIDS-RELATED COMPLEX; HUMAN SOLUBLE CD4;
CLASS-II MHC; HUMAN-ANTIBODY; PHASE-I; ENVELOPE GLYCOPROTEIN;
MONOCLONAL-ANTIBODY; CRYSTAL-STRUCTURE; FUSION PROTEIN
AB Soluble forms of the HIV-1 receptor CD4 (sCD4) have been extensively characterized for more than 2 decades as promising inhibitors and components of vaccine immunogens. However, they were mostly based on the first two CD4 domains (D1D2), and numerous attempts to develop functional, high-affinity, stable soluble one-domain sCD4 (D1) have not been successful because of the strong interactions between the two domains. We have hypothesized that combining the power of structure-based design with sequential panning of large D1 mutant libraries against different HIV-1 envelope glycoproteins (Envs) and screening for soluble mutants could not only help solve the fundamental stability problem of isolated D1, but may also allow improvement of D1 affinity while preserving its cross-reactivity. By using this strategy, we identified two stable monomeric D1 mutants, mD1.1 and mD1.2, which were significantly more soluble and bound Env gp120s more strongly (50-fold) than D1D2, neutralized a panel of HIV-1 primary isolates from different clades more potently than D1D2, induced conformational changes in gp120, and sensitized HIV-1 for neutralization by CD4-induced antibodies. mD1.1 and mD1.2 exhibited much lower binding to human blood cell lines than D1D2; moreover, they preserved a beta-strand secondary structure and stability against thermally induced unfolding, trypsin digestion, and degradation by human serum. Because of their superior properties, mD1.1 and mD1.2 could be potentially useful as candidate therapeutics, components of vaccine immunogens, and research reagents for exploration of HIV-1 entry and immune responses. Our approach could be applied to other cases where soluble isolated protein domains are needed.
C1 [Chen, Weizao; Feng, Yang; Gong, Rui; Zhu, Zhongyu; Wang, Yanping; Zhao, Qi; Dimitrov, Dimiter S.] NCI, Prot Interact Grp, Ctr Canc Res Nanobiol Program, NIH, Frederick, MD 21702 USA.
[Wang, Yanping] NCI, Basic Res Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA.
RP Dimitrov, DS (reprint author), Miller Dr,Bldg 469,Room 150B, Frederick, MD 21702 USA.
EM dimiter.dimitrov@nih.gov
FU National Institutes of Health (NIH); NIH, National Cancer Institute,
Center for Cancer Research; Gates Foundation
FX This project was supported by the Intramural AIDS Targeted Antiviral
Program of the National Institutes of Health (NIH); by the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research; and by the Gates Foundation (D.S.D.).
NR 42
TC 13
Z9 13
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD SEP
PY 2011
VL 85
IS 18
BP 9395
EP 9405
DI 10.1128/JVI.05119-11
PG 11
WC Virology
SC Virology
GA 808DM
UT WOS:000293956400014
PM 21715496
ER
PT J
AU Winstone, N
Wilson, AJ
Morrow, G
Boggiano, C
Chiuchiolo, MJ
Lopez, M
Kemelman, M
Ginsberg, AA
Mullen, K
Coleman, JW
Wu, CD
Narpala, S
Ouellette, I
Dean, HJ
Lin, F
Sardesai, NY
Cassamasa, H
McBride, D
Felber, BK
Pavlakis, GN
Schultz, A
Hudgens, MG
King, CR
Zamb, TJ
Parks, CL
McDermott, AB
AF Winstone, Nicola
Wilson, Aaron J.
Morrow, Gavin
Boggiano, Cesar
Chiuchiolo, Maria J.
Lopez, Mary
Kemelman, Marina
Ginsberg, Arielle A.
Mullen, Karl
Coleman, John W.
Wu, Chih-Da
Narpala, Sandeep
Ouellette, Ian
Dean, Hansi J.
Lin, Feng
Sardesai, Niranjan Y.
Cassamasa, Holly
McBride, Dawn
Felber, Barbara K.
Pavlakis, George N.
Schultz, Alan
Hudgens, Michael G.
King, C. Richter
Zamb, Timothy J.
Parks, Christopher L.
McDermott, Adrian B.
TI Enhanced Control of Pathogenic Simian Immunodeficiency Virus SIVmac239
Replication in Macaques Immunized with an Interleukin-12 Plasmid and a
DNA Prime-Viral Vector Boost Vaccine Regimen
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IN-VIVO ELECTROPORATION; LOW-DOSE CHALLENGE; T-CELL RESPONSES; RHESUS
MACAQUES; DISEASE PROGRESSION; ADENOVIRUS VECTOR; SIV CHALLENGE; HIV-1;
EFFECTOR; MONKEYS
AB DNA priming has previously been shown to elicit augmented immune responses when administered by electroporation (EP) or codelivered with a plasmid encoding interleukin-12 (pIL-12). We hypothesized that the efficacy of a DNA prime and recombinant adenovirus 5 boost vaccination regimen (DNA/rAd5) would be improved when incorporating these vaccination strategies into the DNA priming phase, as determined by pathogenic simian immunodeficiency virus SIVmac239 challenge outcome. The whole SIVmac239 proteome was delivered in 5 separate DNA plasmids (pDNA-SIV) by EP with or without pIL-12, followed by boosting 4 months later with corresponding rAd5-SIV vaccine vectors. Remarkably, after repeated low-dose SIVmac239 mucosal challenge, we demonstrate 2.6 and 4.4 log reductions of the median SIV peak and set point viral loads in rhesus macaques (RMs) that received pDNA-SIV by EP with pIL-12 compared to the median peak and set point viral loads in mock-immunized controls (P < 0.01). In 5 out of 6 infected RMs, strong suppression of viremia was observed, with intermittent "blips" in virus replication. In 2 RMs, we could not detect the presence of SIV RNA in tissue and lymph nodes, even after 13 viral challenges. RMs immunized without pIL-12 demonstrated a typical maximum of 1.5 log reduction in virus load. There was no significant difference in the overall magnitude of SIV-specific antibodies or CD8 T-cell responses between groups; however, pDNA delivery by EP with pIL-12 induced a greater magnitude of SIV-specific CD4 T cells that produced multiple cytokines. This vaccine strategy is relevant for existing vaccine candidates entering clinical evaluation, and this model may provide insights into control of retrovirus replication.
C1 [Winstone, Nicola; Wilson, Aaron J.; Morrow, Gavin; Boggiano, Cesar; Chiuchiolo, Maria J.; Lopez, Mary; Kemelman, Marina; Ginsberg, Arielle A.; Mullen, Karl; Coleman, John W.; Narpala, Sandeep; Ouellette, Ian; Dean, Hansi J.; Schultz, Alan; King, C. Richter; Zamb, Timothy J.; Parks, Christopher L.; McDermott, Adrian B.] Brooklyn Army Terminal, Int AIDS Vaccine Initiat, Design & Dev Lab, Brooklyn, NY 11220 USA.
[Wu, Chih-Da; Hudgens, Michael G.] UNC, Gillings Sch Global Publ Hlth, Dept Biostat, Chapel Hill, NC USA.
[Lin, Feng; Sardesai, Niranjan Y.] Inovio Pharmaceut, Blue Bell, PA USA.
[Cassamasa, Holly; McBride, Dawn] Univ Pittsburgh, RIDC, Pittsburgh, PA USA.
[Felber, Barbara K.] NCI, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21701 USA.
[Pavlakis, George N.] NCI, Human Retrovirus Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21701 USA.
RP Winstone, N (reprint author), Brooklyn Army Terminal, Int AIDS Vaccine Initiat, Design & Dev Lab, 140 58th St, Brooklyn, NY 11220 USA.
EM nwinstone@iavi.org
FU NIH NIAID [AI054165-08]; NIH, National Cancer Institute, Center for
Cancer Research; NIH [5R24RR016038]
FX Statistical analyses were partially funded by NIH NIAID R01 grant no.
AI054165-08. This research was supported in part by the Intramural
Research Program of NIH, National Cancer Institute, Center for Cancer
Research. Typing for major histocompatibility type I alleles was
performed with support from NIH grant 5R24RR016038 awarded to David
Watkins.
NR 66
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U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD SEP
PY 2011
VL 85
IS 18
BP 9578
EP 9587
DI 10.1128/JVI.05060-11
PG 10
WC Virology
SC Virology
GA 808DM
UT WOS:000293956400031
PM 21734035
ER
PT J
AU Holmes, EC
AF Holmes, Edward C.
TI What Does Virus Evolution Tell Us About Virus Origins? (vol 85, pg 5247,
2011)
SO JOURNAL OF VIROLOGY
LA English
DT Correction
C1 [Holmes, Edward C.] Penn State Univ, Mueller Lab, Ctr Infect Dis Dynam, Dept Biol, University Pk, PA 16802 USA.
[Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Holmes, EC (reprint author), Penn State Univ, Mueller Lab, Ctr Infect Dis Dynam, Dept Biol, University Pk, PA 16802 USA.
NR 1
TC 0
Z9 0
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD SEP
PY 2011
VL 85
IS 18
BP 9655
EP 9655
DI 10.1128/JVI.05689-11
PG 1
WC Virology
SC Virology
GA 808DM
UT WOS:000293956400040
ER
PT J
AU Merkle, H
Murphy-Boesch, J
van Gelderen, P
Wang, SM
Li, TQ
Koretsky, AP
Duyn, JH
AF Merkle, Hellmut
Murphy-Boesch, Joseph
van Gelderen, Peter
Wang, Shumin
Li, Tie-Qiang
Koretsky, Alan P.
Duyn, Josef H.
TI Transmit B-1-Field Correction at 7T Using Actively Tuned Coupled Inner
Elements
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE 7T MRI; B-1 field correction; passive B-1 shimming; 7T head phantom
ID ARRAYS; COIL; HEAD; EXCITATION; RESONANCE; IMAGES; POWER
AB When volume coils are used for H-1 imaging of the human head at 7T, wavelength effects in tissue cause a variation in intensity, that is typically brighter at the center of the head and darker in the periphery. Much of this image nonuniformity can be attributed to variation in the effective transmit B-1 field, which falls by similar to 50% to the left and right of center at mid-elevation in the brain. Because most of this B-1 loss occurs in the periphery of the brain, we have explored use of actively controlled, off-resonant loop elements to locally enhance the transmit B-1 field in these regions. When tuned to frequencies above the NMR frequency, these elements provide strong local enhancement of the B-1 field of the transmit coil. Because they are tuned off-resonance, some volume coil detuning results, but resistive loading of the coil mode remains dominated by the sample. By digitally controlling their frequency offsets, the field enhancement of each inner element can be placed under active control. Using an array of eight digitally controlled elements placed around a custom-built head phantom, we demonstrate the feasibility of improving the B-1 homogeneity of a transmit/receive volume coil without the need for multiple radio frequency transmit channels. Magn Reson Med 66:901-910, 2011. (C) 2011 Wiley-Liss, Inc.
C1 [Merkle, Hellmut; Murphy-Boesch, Joseph; van Gelderen, Peter; Wang, Shumin; Li, Tie-Qiang; Koretsky, Alan P.; Duyn, Josef H.] Natl Inst Neurol Disorders & Stroke, NIH, Lab Funct & Mol Imaging, Bethesda, MD USA.
[Wang, Shumin] Auburn Univ, Dept Elect & Comp Engn, Auburn, AL 36849 USA.
[Li, Tie-Qiang] Karolinska Univ Hosp Huddinge, Dept Med Phys, Stockholm, Sweden.
RP Murphy-Boesch, J (reprint author), NINDS, NIH, LFMI, Rm B1D728,10 Ctr Dr, Bethesda, MD 20892 USA.
EM murphyboeschj@mail.nih.gov
RI Koretsky, Alan/C-7940-2015;
OI Koretsky, Alan/0000-0002-8085-4756; Li, Tieqiang/0000-0002-6636-8938;
Li, Tie-Qiang/0000-0002-4866-5904
FU National Institute of Neurological Disorders and Stroke, NIH
FX This research was supported by the National Institute of Neurological
Disorders and Stroke (Intramural Research Program of the NIH).
NR 25
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U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0740-3194
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD SEP
PY 2011
VL 66
IS 3
BP 901
EP 910
DI 10.1002/mrm.22864
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 808OJ
UT WOS:000293988000032
PM 21437974
ER
PT J
AU Strober, W
Watanabe, T
AF Strober, W.
Watanabe, T.
TI NOD2, an intracellular innate immune sensor involved in host defense and
Crohn's disease
SO MUCOSAL IMMUNOLOGY
LA English
DT Review
ID TOLL-LIKE-RECEPTOR; KAPPA-B ACTIVATION; INFLAMMATORY-BOWEL-DISEASE;
MURAMYL DIPEPTIDE; DENDRITIC CELLS; ADAPTIVE IMMUNITY;
MYCOBACTERIUM-TUBERCULOSIS; NEGATIVE REGULATION; CYTOKINE PRODUCTION;
KINASE-ACTIVITY
AB Nucleotide-binding oligomerization domain 2 (NOD2) is an intracellular sensor for small peptides derived from the bacterial cell wall component, peptidoglycan. Recent studies have uncovered unexpected functions of NOD2 in innate immune responses such as induction of type I interferon and facilitation of autophagy; moreover, they have disclosed extensive cross-talk between NOD2 and Toll-like receptors, which has an indispensable role both in host defense against microbial infection and in the development of autoimmunity. Of particular interest, polymorphisms of CARD15 encoding NOD2 are associated with Crohn's disease and other autoimmune states such as graft vs. host disease. In this review, we summarize recent findings regarding normal functions of NOD2 and discuss the mechanisms by which NOD2 polymorphisms associated with Crohn's disease lead to intestinal inflammation.
C1 [Strober, W.] NIAID, Host Def Lab, Mucosal Immun Sect, NIH, Bethesda, MD 20892 USA.
[Watanabe, T.] Kyoto Univ, Dept Gastroenterol, Kyoto, Japan.
RP Strober, W (reprint author), NIAID, Host Def Lab, Mucosal Immun Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM Wstrober@niaid.nih.gov
FU Intramural NIH HHS [Z99 AI999999]
NR 77
TC 60
Z9 63
U1 1
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1933-0219
J9 MUCOSAL IMMUNOL
JI Mucosal Immunol.
PD SEP
PY 2011
VL 4
IS 5
BP 484
EP 495
DI 10.1038/mi.2011.29
PG 12
WC Immunology
SC Immunology
GA 809HC
UT WOS:000294041400002
PM 21750585
ER
PT J
AU Levin, HL
Moran, JV
AF Levin, Henry L.
Moran, John V.
TI Dynamic interactions between transposable elements and their hosts
SO NATURE REVIEWS GENETICS
LA English
DT Review
ID RNA-POLYMERASE-III; HUMAN L1 RETROTRANSPOSITION; INDEPENDENT LINE-1
RETROTRANSPOSITION; TERMINAL REPEAT RETROTRANSPOSON; POSITION-SPECIFIC
INTEGRATION; YEAST TY5 RETROTRANSPOSON; MAMMALIAN GERM-CELLS; EMBRYONIC
STEM-CELLS; VIRUS-LIKE PARTICLES; HUMAN GENOME
AB Transposable elements (TEs) have a unique ability to mobilize to new genomic locations, and the major advance of second-generation DNA sequencing has provided insights into the dynamic relationship between TEs and their hosts. It now is clear that TEs have adopted diverse strategies - such as specific integration sites or patterns of activity - to thrive in host environments that are replete with mechanisms, such as small RNAs or epigenetic marks, that combat TE amplification. Emerging evidence suggests that TE mobilization might sometimes benefit host genomes by enhancing genetic diversity, although TEs are also implicated in diseases such as cancer. Here, we discuss recent findings about how, where and when TEs insert in diverse organisms.
C1 [Levin, Henry L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Eukaryot Transposable Elements, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
[Moran, John V.] Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI 48109 USA.
[Moran, John V.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Moran, John V.] Univ Michigan, Sch Med, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA.
RP Levin, HL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Eukaryot Transposable Elements, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
EM henry_levin@nih.gov; moranj@umich.edu
FU US National Institutes of Health (NIH) from the Eunice Kennedy Shriver
National Institute of Child Health and Human Development; Intramural
AIDS Targeted Antiviral Program; NIH [GM060518, GM082970]
FX We thank J. Kim, J. Garcia-Perez and members of the Moran laboratory for
critical reading of the manuscript. H.L.L. was supported in part by the
Intramural Research Program of the US National Institutes of Health
(NIH) from the Eunice Kennedy Shriver National Institute of Child Health
and Human Development. He received additional support from the
Intramural AIDS Targeted Antiviral Program. J.V.M. was supported in part
by grants from the NIH (GM060518 and GM082970) and is an Investigator of
the Howard Hughes Medical Institute.
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PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-0056
EI 1471-0064
J9 NAT REV GENET
JI Nat. Rev. Genet.
PD SEP
PY 2011
VL 12
IS 9
BP 615
EP 627
DI 10.1038/nrg3030
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA 808UH
UT WOS:000294004100008
PM 21850042
ER
PT J
AU Li, YT
Li, SC
Buck, WR
Haskins, ME
Wu, SW
Khoo, KH
Sidransky, E
Bunnell, BA
AF Li, Yu-Teh
Li, Su-Chen
Buck, Wayne R.
Haskins, Mark E.
Wu, Sz-Wei
Khoo, Kay-Hooi
Sidransky, Ellen
Bunnell, Bruce A.
TI Selective Extraction and Effective Separation of Galactosylsphingosine
(Psychosine) and Glucosylsphingosine from Other Glycosphingolipids in
Pathological Tissue Samples
SO NEUROCHEMICAL RESEARCH
LA English
DT Article
DE Galactosylsphingosine; Psychosine; Glucosylsphingosine; Krabbe disease;
Gaucher disease
ID GLOBOID-CELL LEUKODYSTROPHY; TYPE-2 GAUCHER-DISEASE; KRABBE-DISEASE;
ACCUMULATION; QUANTIFICATION; CHROMATOGRAPHY; BRAIN; LIVER
AB To facilitate the study of the chemical pathology of galactosylsphingosine (psychosine, GalSph) in Krabbe disease and glucosylsphingosine (GlcSph) in Gaucher disease, we have devised a facile method for the effective separation of these two glycosylsphingosines from other glycosphingolipids (GSLs) in Krabbe brain and Gaucher spleen samples. The procedure involves the use of acetone to selectively extract GalSph and GlcSph, respectively, from Krabbe brain and Gaucher spleen samples. Since acetone does not extract other GSLs except modest amounts of galactosylceramide, sulfatide, and glucosylceramide, the positively charged GalSph or GlcSph in the acetone extract can be readily separated from other GSLs by batchwise cation-exchange chromatography using a Waters Accell Plus CM Cartridge. GalSph or GlcSph enriched by this simple procedure can be readily analyzed by thin-layer chromatography or high-performance liquid chromatography.
C1 [Li, Yu-Teh; Li, Su-Chen] Tulane Univ, Sch Med, Dept Biochem, New Orleans, LA 70112 USA.
[Buck, Wayne R.] Tulane Natl Primate Res Ctr, Dept Pathol, Covington, LA USA.
[Haskins, Mark E.] Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA.
[Wu, Sz-Wei; Khoo, Kay-Hooi] Acad Sinica, Inst Biol Chem, Taipei, Taiwan.
[Sidransky, Ellen] Natl Genome Res Inst, Sect Mol Neurogenet, Med Genet Branch, NIH, Bethesda, MD USA.
[Bunnell, Bruce A.] Tulane Univ, Sch Med, Ctr Gene Therapy, New Orleans, LA 70112 USA.
[Bunnell, Bruce A.] Tulane Natl Primate Res Ctr, Div Gene Therapy, Covington, LA USA.
[Bunnell, Bruce A.] Tulane Univ, Sch Med, Dept Pharmacol, New Orleans, LA 70112 USA.
RP Li, YT (reprint author), Tulane Univ, Sch Med, Dept Biochem, 1430 Tulane Ave,SL-43, New Orleans, LA 70112 USA.
EM yli1@tulane.edu
FU NIH [R01 NS09626, RR02512, NCRR R24RR022826]; Louisiana Gene Therapy
Research Consortium Tulane University; NSC [NSC98-3112-B-001-023]
FX This study was supported by NIH grant R01 NS09626 (to YT Li), NIH grant
RR02512 (to ME Haskins), NIH grant NCRR R24RR022826 and Louisiana Gene
Therapy Research Consortium Tulane University (to B. Bunnell). The human
brain samples from Krabbe patients and the age matched control subjects
were obtained from the NICHD Brain and Tissue Bank for Developmental
Disorders at the University of Maryland, Baltimore, MD. MALDI-MS
analyses were performed at the NRPGM Core Facilities for Proteomics and
Glycomics, Institute of Biological Chemistry, Academia Sinica, Taiwan,
supported by an NSC grant NSC98-3112-B-001-023.
NR 19
TC 6
Z9 6
U1 0
U2 7
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-3190
J9 NEUROCHEM RES
JI Neurochem. Res.
PD SEP
PY 2011
VL 36
IS 9
SI SI
BP 1612
EP 1622
DI 10.1007/s11064-010-0348-3
PG 11
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 808DO
UT WOS:000293956800006
PM 21136152
ER
PT J
AU Chefer, VI
Wang, RZ
Shippenberg, TS
AF Chefer, Vladimir I.
Wang, Ruizhong
Shippenberg, Toni S.
TI Basolateral Amygdala-Driven Augmentation of Medial Prefrontal Cortex
GABAergic Neurotransmission in Response to Environmental Stimuli
Associated with Cocaine Administration
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE basolateral amygdala; cocaine; drug-associated environment; glutamate;
GABA; medial prefrontal cortex
ID VENTRAL TEGMENTAL AREA; ELICITED DRUG SEEKING; BEHAVIORAL SENSITIZATION;
GABA TRANSMISSION; RAT; NEURONS; HIPPOCAMPUS; ACTIVATION; ADDICTION;
GLUTAMATE
AB Basolateral amygdala (BLA) and medial prefrontal cortex (mPFC) interactions have been implicated in cue-elicited craving and drug seeking. However, the neurochemical mechanisms underlying drug/environment associations are ill-defined. We used in vivo microdialysis and pharmacological inactivation techniques to identify alterations in mPFC glutamate (GLU) and gamma-aminobutyric acid (GABA) transmission in response to cues previously associated with experimenter-administered cocaine (COC) and the BLA contribution to these effects. Rats received alternate day injections of COC and saline (SAL) paired with a distinct environment for 6 days. Behavioral, neurochemical and immunohistochemical studies were conducted, in drug-free animals, 24 h after the last conditioning session. Animals exposed to a COC-paired environment demonstrated an augmented locomotor activity (LMA) relative to those exposed to the SAL-paired environment. mPFC GABA neurotransmission in the COC-paired environment was significantly increased, whereas GLU overflow was unaltered. Dual labeling of cFos and glutamic acid decarboxylase 67 immunoreactivity in mPFC neurons revealed significantly greater colocalization of these proteins following exposure to the COC-associated environment (CAE) relative to pseudo-conditioned rats or rats exposed to the SAL-associated environment indicating that the conditioned neurochemical response to the COC-paired environment is associated with activation of intrinsic mPFC GABA neurons. BLA inactivation prevented the increase in LMA and the augmentation of mPFC GABA transmission produced by cue exposure. Intra-mPFC application of the AMPA/KA receptor antagonist, NBQX, produced similar effects. These findings indicate that exposure to a CAE increases mPFC GABA transmission by enhancing excitatory drive from the BLA and activation of AMPA/KA receptors on mPFC GABA neurons. Neuropsychopharmacology (2011) 36, 2018-2029; doi: 10.1038/npp.2011.89; published online 1 June 2011
C1 [Chefer, Vladimir I.; Wang, Ruizhong; Shippenberg, Toni S.] Natl Inst Drug Abuse, Integrat Neurosci Sect, Integrat Neurosci Branch, NIH,Intramural Res Program, Baltimore, MD 21224 USA.
RP Chefer, VI (reprint author), Natl Inst Drug Abuse, Integrat Neurosci Sect, Integrat Neurosci Branch, NIH,Intramural Res Program, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM vchefer@intra.nida.nih.gov
FU US National Institutes of Health; National Institute on Drug Abuse
FX This work was supported by the US National Institutes of Health, the
National Institute on Drug Abuse Intramural Research Program.
NR 42
TC 8
Z9 8
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD SEP
PY 2011
VL 36
IS 10
BP 2018
EP 2029
DI 10.1038/npp.2011.89
PG 12
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 807JM
UT WOS:000293893100007
PM 21633339
ER
PT J
AU Lenoir, M
Kiyatkin, EA
AF Lenoir, Magalie
Kiyatkin, Eugene A.
TI Critical Role of Peripheral Actions of Intravenous Nicotine in Mediating
Its Central Effects
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE electroencephalography; electromyography; field potentials; peripheral
nicotinic receptors; sensory signal; learning
ID SENSORY NERVE-ENDINGS; ACETYLCHOLINE-RECEPTORS; EEG DESYNCHRONIZATION;
NEURONS; RAT; ADDICTION; RESPONSES; BRAIN; CHEMORECEPTORS;
MONOMETHIODIDE
AB In addition to its direct action on central neurons, nicotine (NIC) activates multiple nicotinic acetylcholine receptors localized on afferent terminals of sensory nerves at the sites of its administration. Although the activation of these receptors is important in mediating the primary sensory and cardiovascular effects of NIC, their role in triggering and maintaining the neural effects of NIC remains unclear. Using high-speed electroencephalography (EEG) and electromyography (EMG) recordings in freely moving rats, we showed that NIC at low intravenous (i.v.) doses (10-30 mu g/kg) induced rapid, strong, and prolonged EEG desynchronization both in the cortex and ventral tegmental area (with decreases in alpha and robust increases in beta and gamma frequencies) and neck EMG activation that began during the injection (similar to 5 s). EEG and EMG effects of NIC were drastically reduced by pre-treatment with hexamethonium, a peripherally acting NIC antagonist, and the immediate EEG effects of NIC were strongly inhibited during urethane anesthesia. Although NIC pyrrolidine methiodide, a quaternary NIC analog that cannot enter the brain, also induced rapid EEG desynchronization, its effects were much shorter and weaker than those of NIC. Therefore, NIC by acting on peripheral nicotinic receptors provides a major contribution to its rapid, excitatory effects following i.v. administration. Since this action creates a sensory signal that rapidly reaches the brain via neural pathways and precedes the slower and more prolonged direct actions of NIC on brain cells, it could have a major role in associative learning and changes in the behavioral and physiological effects of NIC following its repeated use. Neuropsychopharmacology (2011) 36, 2125-2138; doi: 10.1038/npp.2011.104; published online 8 June 2011
C1 [Kiyatkin, Eugene A.] Natl Inst Drug Abuse, In Vivo Electrophysiol Unit, Behav Neurosci Branch, Intramural Res Program,NIH,DHHS, Baltimore, MD 21224 USA.
RP Kiyatkin, EA (reprint author), Natl Inst Drug Abuse, 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 NIH, NIDA
FX The research described in this manuscript was supported by the
Intramural Research Program of the NIH, NIDA. We thank Drs Charles
Spivak, Serge Ahmed, and Alexey Mukhin for valuable comments regarding
scientific issues and Jeremy Tang for assistance in editing of this
manuscript.
NR 43
TC 9
Z9 9
U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD SEP
PY 2011
VL 36
IS 10
BP 2125
EP 2138
DI 10.1038/npp.2011.104
PG 14
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 807JM
UT WOS:000293893100017
PM 21654739
ER
PT J
AU Stamatelli, A
Saetta, AA
Bei, T
Kavantzas, N
Michalopoulos, NV
Patsouris, E
Aroni, K
AF Stamatelli, Angeliki
Saetta, Angelica A.
Bei, Thaleia
Kavantzas, Nicolaos
Michalopoulos, Nicolaos V.
Patsouris, Efstratios
Aroni, Kiriaki
TI B-Raf Mutations, Microsatellite Instability and p53 Protein Expression
in Sporadic Basal Cell Carcinomas
SO PATHOLOGY & ONCOLOGY RESEARCH
LA English
DT Article
DE Basal cell carcinoma; B-Raf; Microsatellite instability; p53; Skin
ID P53-PROTEIN EXPRESSION; HISTOLOGIC VARIANTS; SKIN TUMORS; BRAF GENE;
CANCER; TARGETS; DNA
AB Basal Cell Carcinoma (BCC) is the most common skin malignancy. Genes related to the Ras/Raf signalling pathway have been implicated in the pathogenesis of skin cancer. The objective of this study was to investigate the presence of B-Raf mutations in sporadic BCCs as well as its correlation with the phenotype of microsatellite instability (MSI), the clinicopathological parameters of the tumours and p53 protein expression. 83 BCC specimens were screened for B-Raf mutations, applying polymerase chain reaction, single-stranded conformation polymorphism (PCR-SSCP) and DNA sequencing. MSI status was examined using mononucleotide microsatellite markers and p53 protein expression was demonstrated by immunohistochemical staining. A C to T transition at 1790 nucleotide leading to a silent mutation L597L; and a T to A transversion causing an amino acid change (F610I) have been found. MSI was detected in 5% of the cases and p53 accumulation was present in 37/83 samples studied. Although rare B-Raf alterations have been observed in BCC, none of them harboured the hot-spot mutation T1799A commonly present in melanomas and colon carcinomas. Consequently, no correlation could be determined between B-Raf alterations, MSI status, the clinicopathological features and p53 protein expression. Our results are in favour of a secondary importance for Ras signalling cascade genes in BCC pathogenesis.
C1 [Stamatelli, Angeliki; Saetta, Angelica A.; Kavantzas, Nicolaos; Michalopoulos, Nicolaos V.; Patsouris, Efstratios; Aroni, Kiriaki] Univ Athens, Sch Med, Dept Pathol 1, GR-11527 Athens, Greece.
[Bei, Thaleia] NICHHD, Sect Endocrinol & Genet, DEB, NIH, Bethesda, MD 20892 USA.
RP Stamatelli, A (reprint author), Univ Athens, Sch Med, Dept Pathol 1, 75 Mikras Asias Str, GR-11527 Athens, Greece.
EM agstam@med.uoa.gr
NR 29
TC 3
Z9 3
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1219-4956
J9 PATHOL ONCOL RES
JI Pathol. Oncol. Res.
PD SEP
PY 2011
VL 17
IS 3
BP 633
EP 637
DI 10.1007/s12253-011-9363-1
PG 5
WC Oncology; Pathology
SC Oncology; Pathology
GA 809OY
UT WOS:000294067800024
PM 21274671
ER
PT J
AU Lin, FYC
Weisman, LE
Azimi, P
Young, AE
Chang, K
Cielo, M
Moyer, P
Troendle, JF
Schneerson, R
Robbins, JB
AF Lin, Feng-Ying C.
Weisman, Leonard E.
Azimi, Parvin
Young, Amy E.
Chang, Kathleen
Cielo, Mikhaela
Moyer, Patricia
Troendle, James F.
Schneerson, Rachel
Robbins, John B.
TI Assessment of Intrapartum Antibiotic Prophylaxis for the Prevention of
Early-onset Group B Streptococcal Disease
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Article
DE group B Streptococcus; early onset disease; predictive values; prenatal
cultures; intrapartum antibiotic prophylaxis
ID POLYMERASE-CHAIN-REACTION; PREDICTIVE VALUE; COLONIZATION; CULTURES;
WOMEN; ACCURACY; ERA
AB Background: Most early-onset group B streptococcal (GBS) disease in recent years has occurred in newborns of prenatally GBS-negative mothers who missed intrapartum antibiotic prophylaxis (IAP). We aimed to assess the accuracy of prenatal culture in predicting GBS carriage during labor, the IAP use, and occurrence of early-onset GBS disease.
Methods: We obtained vaginal-rectal swabs at labor for GBS culture from 5497 women of >= 32 weeks' gestation and surface cultures at birth from newborns between February 5, 2008 and February 4, 2009 at 3 hospitals in Houston, TX and Oakland, CA. Prenatal cultures were performed by a healthcare provider during routine care, and culture results were obtained from medical records. The accuracy of prenatal culture in predicting intrapartum GBS carriage was assessed by positive and negative predictive values. Mother-to-newborn transmission of GBS was assessed. Newborns were monitored for early-onset GBS disease.
Results: GBS carriage was 24.5% by prenatal and 18.8% by labor cultures. Comparing prenatal with labor GBS cultures of 4696 women, the positive predictive value was 50.5% and negative predictive value was 91.7%. IAP, administered to 93.3% of prenatally GBS-positive women, was 83.7% effective in preventing newborn's GBS colonization. Mother-to-newborn transmission of GBS occurred in 2.6% of elective cesarean deliveries. Two newborns developed early-onset GBS disease (0.36/1000 births); the prenatal GBS culture of one was negative, the other's was unknown.
Conclusions: IAP was effective in interrupting mother-to-newborn transmission of GBS. However, approximately 10% of prenatally GBS-negative women were positive during labor and missed IAP, whereas approximately 50% of prenatally GBS-positive women were negative during labor and received IAP. These findings emphasize the need for rapid diagnostics during labor.
C1 [Lin, Feng-Ying C.; Moyer, Patricia; Schneerson, Rachel; Robbins, John B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Lin, Feng-Ying C.; Moyer, Patricia; Schneerson, Rachel; Robbins, John B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA.
[Weisman, Leonard E.; Young, Amy E.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
[Weisman, Leonard E.; Young, Amy E.] Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA.
[Azimi, Parvin; Chang, Kathleen; Cielo, Mikhaela] Childrens Hosp & Res Ctr, Oakland, CA USA.
[Troendle, James F.] NHLBI, Div Cardiovasc Sci, Off Biostat Res, NIH, Bethesda, MD 20892 USA.
RP Lin, FYC (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Res, NIH, 31 Ctr Dr,Rm 2A25, Bethesda, MD 20892 USA.
EM Link@mail.nih.gov
FU Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health
FX Supported by the Intramural Research Program, Division of Intramural
Research, Eunice Kennedy Shriver National Institute of Child Health and
Human Development, National Institutes of Health.
NR 31
TC 23
Z9 25
U1 1
U2 4
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 2011
VL 30
IS 9
BP 759
EP 763
DI 10.1097/INF.0b013e31821dc76f
PG 5
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA 809IF
UT WOS:000294044400010
PM 21540758
ER
PT J
AU Mirochnick, M
Nielsen-Saines, K
Pilotto, JH
Pinto, J
Veloso, VG
Rossi, S
Moye, J
Bryson, Y
Mofenson, L
Camarca, M
Watts, DH
AF Mirochnick, Mark
Nielsen-Saines, Karin
Pilotto, Jose Henrique
Pinto, Jorge
Veloso, Valdilea Goncalves
Rossi, Steven
Moye, Jack
Bryson, Yvonne
Mofenson, Lynne
Camarca, Margaret
Heather Watts, D.
CA NICHD HPTN 040-PACTG 1043 PROTOCO
TI Nelfinavir and Lamivudine Pharmacokinetics During the First Two Weeks of
Life
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Article
DE nelfinavir; lamivudine; pharmacokinetics; newborns
ID IMMUNODEFICIENCY-VIRUS TYPE-1; HYDROXY-TERT-BUTYLAMIDE; ACTIVE
METABOLITE; INFECTED INFANTS; SAFETY; ZIDOVUDINE; INHIBITOR; CHILDREN;
AGE
AB Background: There are no previous data describing nelfinavir and lamivudine pharmacokinetics in neonates treated with weight-band dosing regimens.
Design: Pharmacokinetic study of nelfinavir and lamivudine pharmacokinetics in infants during the first 2 weeks of life treated with weight-band dosing regimens.
Methods: Intensive 12-hour pharmacokinetic profiles were performed between either days 4-7 or days 10-14 of life in 26 Brazilian infants.
Results: Pharmacokinetic data were obtained from 26 infants who received median (range) per kg doses of 58.8 (48.4-79.0) mg/kg for nelfinavir and 2.0 (1.5-3.2) mg/kg for lamivudine. Median nelfinavir 12-hour AUC (AUC0-12) was 25.5 (1.7-183.5) mu g*h/mL and median 12-hour concentration (C12h) was 1.09 (< 0.04-14.44) mu g/mL. AUC0-12 was less than 15 mu g*h/mL (the 10% for adults) in 12 infants (46%). Median lamivudine AUC0-12 was 7.8 (2.7-15.6) mu g*h/mL and median C12h was 0.23 (< 0.04-0.74) mu g/mL.
Conclusions: Lamivudine pharmacokinetic parameters observed in this study were consistent with those seen in other studies of neonates. While median nelfinavir AUC and C12h in these neonates were above the exposure targets, interindividual variability in nelfinavir exposure was large and nelfinavir exposure failed to meet the exposure targets in 46% of infants.
C1 [Mirochnick, Mark] Boston Univ, Sch Med, Dept Pediat, Boston Med Ctr, Boston, MA 02118 USA.
[Nielsen-Saines, Karin; Bryson, Yvonne] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90095 USA.
[Pilotto, Jose Henrique] Hosp Geral de Nova Iguacu, Dept Infect Dis, Nova Iguacu, Brazil.
[Pilotto, Jose Henrique] Fiocruz MS, Lab AIDS & Imunol Mol, BR-21045900 Rio De Janeiro, Brazil.
[Pinto, Jorge] Univ Fed Minas Gerais, Dept Pediat, Div Immunol, Belo Horizonte, MG, Brazil.
[Veloso, Valdilea Goncalves] Fiocruz Inst, Inst Pesquias Clin Evandro Chagas, Rio De Janeiro, Brazil.
[Rossi, Steven] Univ Calif San Diego, Sch Med, Dept Pediat, La Jolla, CA 92093 USA.
[Moye, Jack] NICHD, Natl Childrens Study, NIH, DHHS, Bethesda, MD USA.
[Mofenson, Lynne; Heather Watts, D.] NICHD, Adolescent & Maternal AIDS Branch, NIH, DHHS, Bethesda, MD USA.
[Camarca, Margaret] Westat Corp, Clin Trials Area, Rockville, MD USA.
RP Mirochnick, M (reprint author), Boston Univ, Sch Med, Dept Pediat, Boston Med Ctr, 771 Albany St,Dowling 4N,Room 4111, Boston, MA 02118 USA.
EM markm@bu.edu
RI Goncalves Veloso, Valdilea/J-6189-2012;
OI Mofenson, Lynne/0000-0002-2818-9808; moye, john/0000-0001-9976-8586
FU NICHD [HHSN267200800001C, N01-HD-8-0001]; Eunice Kennedy Shriver
National Institute of Child Health and Human Development [NO1-HD33345];
HIV Prevention Trials Network (HPTN); (IMPAACT) Group
FX Supported by NICHD Contract HHSN267200800001C (NICHD Control
N01-HD-8-0001) and by the Eunice Kennedy Shriver National Institute of
Child Health and Human Development (contract NO1-HD33345), and
co-sponsored by the HIV Prevention Trials Network (HPTN) and the
International Maternal Pediatric Adolescent AIDS Clinical Trials
(IMPAACT) Group.
NR 16
TC 11
Z9 11
U1 0
U2 1
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 2011
VL 30
IS 9
BP 769
EP 772
DI 10.1097/INF.0b013e3182242950
PG 4
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA 809IF
UT WOS:000294044400012
PM 21666540
ER
PT J
AU Freeman, AF
Marciano, BE
Anderson, VL
Uzel, G
Costas, C
Holland, SM
AF Freeman, Alexandra F.
Marciano, Beatriz E.
Anderson, Victoria L.
Uzel, Gulbu
Costas, Christ
Holland, Steven M.
TI CORTICOSTEROIDS IN THE TREATMENT OF SEVERE NOCARDIA PNEUMONIA IN CHRONIC
GRANULOMATOUS DISEASE
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Article
DE chronic granulomatous disease; Nocardia pneumonia
ID INFECTION; THERAPY
AB Nocardia is 1 of the 5 main pathogens that infect chronic granulomatous disease patients. Despite aggressive antimicrobial therapy, medical treatment is not always successful and surgical resection of infected tissue has been intermittently required. We present 2 chronic granulomatous disease patients with severe Nocardia pneumonia whose pulmonary status worsened despite appropriate antimicrobials, but then improved clinically and radiographically with the addition of corticosteroids.
C1 [Freeman, Alexandra F.; Marciano, Beatriz E.; Anderson, Victoria L.; Uzel, Gulbu; Holland, Steven M.] NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Costas, Christ] St Francis Hosp, Evanston, IL USA.
RP Freeman, AF (reprint author), NIH Bldg 10,Room 11N234,10 Ctr Dr, Bethesda, MD 20892 USA.
EM freemaal@niaid.nih.gov
FU Division of Intramural Research of the NIAID, NIH, Bethesda, MD
FX Supported by the Division of Intramural Research of the NIAID, NIH,
Bethesda, MD 20892.
NR 11
TC 7
Z9 7
U1 1
U2 1
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 2011
VL 30
IS 9
BP 806
EP 808
DI 10.1097/INF.0b013e318218181d
PG 3
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA 809IF
UT WOS:000294044400024
PM 21412179
ER
PT J
AU Mattoo, T
Carpenter, M
Chesney, R
Greenfield, S
Hoberman, A
Keren, R
Mathews, R
Moxey-Mims, M
AF Mattoo, T.
Carpenter, M.
Chesney, R.
Greenfield, S.
Hoberman, A.
Keren, R.
Mathews, R.
Moxey-Mims, M.
TI Screening and enrolling children with vesicoureteral reflux: preliminary
data from the RIVUR trial
SO PEDIATRIC NEPHROLOGY
LA English
DT Meeting Abstract
C1 [Mattoo, T.] Childrens Hosp Michigan, Detroit, MI USA.
[Carpenter, M.] Univ N Carolina, Chapel Hill, NC 27515 USA.
[Chesney, R.] Univ Tennessee, Knoxville, TN 37996 USA.
[Greenfield, S.] Womens & Childrens Hosp Buffalo, Buffalo, NY USA.
[Hoberman, A.; Keren, R.] Childrens Hosp Pittsburgh, Pittsburgh, PA USA.
[Mathews, R.] Johns Hopkins Sch Med, Baltimore, MD USA.
[Moxey-Mims, M.] NIDDK, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0931-041X
J9 PEDIATR NEPHROL
JI Pediatr. Nephrol.
PD SEP
PY 2011
VL 26
IS 9
BP 1729
EP 1730
PG 2
WC Pediatrics; Urology & Nephrology
SC Pediatrics; Urology & Nephrology
GA 798YT
UT WOS:000293248800531
ER
PT J
AU Bindewald, E
Wendeler, M
Legiewicz, M
Bona, MK
Wang, Y
Pritt, MJ
Le Grice, SFJ
Shapiro, BA
AF Bindewald, Eckart
Wendeler, Michaela
Legiewicz, Michal
Bona, Marion K.
Wang, Yi
Pritt, Mark J.
Le Grice, Stuart F. J.
Shapiro, Bruce A.
TI Correlating SHAPE signatures with three-dimensional RNA structures
SO RNA-A PUBLICATION OF THE RNA SOCIETY
LA English
DT Article
DE 3D structures; RNA; SHAPE signatures; context sensitivity; probabilistic
models
ID SELECTIVE 2'-HYDROXYL ACYLATION; SINGLE NUCLEOTIDE RESOLUTION; PRIMER
EXTENSION SHAPE; SECONDARY STRUCTURE; RIBOSWITCHES; QUANTIFICATION;
CLASSIFICATION; INFORMATION; SOFTWARE
AB Selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) is a facile technique for quantitative analysis of RNA secondary structure. In general, low SHAPE signal values indicate Watson-Crick base-pairing, and high values indicate positions that are single-stranded within the RNA structure. However, the relationship of SHAPE signals to structural properties such as non-Watson-Crick base-pairing or stacking has thus far not been thoroughly investigated. Here, we present results of SHAPE experiments performed on several RNAs with published three-dimensional structures. This strategy allows us to analyze the results in terms of correlations between chemical reactivities and structural properties of the respective nucleotide, such as different types of base-pairing, stacking, and phosphate-backbone interactions. We find that the RNA SHAPE signal is strongly correlated with cis-Watson-Crick/Watson-Crick base-pairing and is to a remarkable degree not dependent on other structural properties with the exception of stacking. We subsequently generated probabilistic models that estimate the likelihood that a residue with a given SHAPE score participates in base-pairing. We show that several models that take SHAPE scores of adjacent residues into account perform better in predicting base-pairing compared with individual SHAPE scores. This underscores the context sensitivity of SHAPE and provides a framework for an improved interpretation of the response of RNA to chemical modification.
C1 [Pritt, Mark J.; Shapiro, Bruce A.] NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA.
[Bindewald, Eckart; Bona, Marion K.] NCI, Basic Sci Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Wendeler, Michaela; Legiewicz, Michal; Wang, Yi; Le Grice, Stuart F. J.] NCI, RT Biochem Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA.
RP Shapiro, BA (reprint author), NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA.
EM shapirbr@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer
Research
FX This work 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. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 29
TC 19
Z9 19
U1 0
U2 3
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1355-8382
J9 RNA
JI RNA-Publ. RNA Soc.
PD SEP
PY 2011
VL 17
IS 9
BP 1688
EP 1696
DI 10.1261/rna.2640111
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 808GF
UT WOS:000293964600008
PM 21752927
ER
PT J
AU Hong, SH
Osborne, T
Ren, L
Briggs, J
Mazcko, C
Burkett, SS
Khanna, C
AF Hong, S. -H.
Osborne, T.
Ren, L.
Briggs, J.
Mazcko, C.
Burkett, S. S.
Khanna, C.
TI Protein kinase C regulates ezrin-radixin-moesin phosphorylation in
canine osteosarcoma cells
SO VETERINARY AND COMPARATIVE ONCOLOGY
LA English
DT Article
DE dog; ezrin; metastasis; osteosarcoma; PKC
ID GENE-EXPRESSION; CARCINOMA-CELLS; LINKER EZRIN; METASTASIS; TUMORS;
MODEL; MELANOMA; SURVIVAL; BIOLOGY; DOG
AB The development of metastasis is the most significant cause of death for both canine and human patients with osteosarcoma (OS). Ezrin has been associated with tumour progression and metastasis in human, canine and murine OS. Ezrin activation is dynamically regulated by protein kinase C (PKC) during metastatic progression in human and murine OS. To include the dog in the development of therapeutics that target ezrin biology, we characterized four new canine OS cell lines and confirmed the relationship between PKC and ezrin in these cells. Three of four cell lines formed tumours in mice that were histologically consistent with OS. All cell lines were markedly aneuploid and expressed ezrin and PKC. Finally, both ezrin phosphorylation and cell migration were inhibited using a PKC inhibitor. These data suggest that an association between PKC-mediated activation of ezrin and the metastatic phenotype in canine OS cells.
C1 [Hong, S. -H.; Osborne, T.; Ren, L.; Briggs, J.; Khanna, C.] NCI, Tumor & Metastasis Biol Sect, Pediat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Mazcko, C.; Khanna, C.] NCI, Comparat Oncol Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Burkett, S. S.] NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21701 USA.
RP Hong, SH (reprint author), NCI, Tumor & Metastasis Biol Sect, Pediat Oncol Branch, Ctr Canc Res,NIH, 37 Convent Dr, Bethesda, MD 20892 USA.
EM hongsu@mail.nih.gov
FU American Kennel Club Canine Health Foundation [1046-A]
FX This project was supported by a grant (1046-A) from the American Kennel
Club Canine Health Foundation. The contents of this publication are
solely the responsibility of the authors and do not necessarily
represent the views of the Foundation.
NR 29
TC 15
Z9 15
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1476-5810
J9 VET COMP ONCOL
JI Vet. Comp. Oncol.
PD SEP
PY 2011
VL 9
IS 3
BP 207
EP 218
DI 10.1111/j.1476-5829.2010.00249.x
PG 12
WC Veterinary Sciences
SC Veterinary Sciences
GA 808ZH
UT WOS:000294020000005
PM 21848623
ER
PT J
AU Shmulewitz, D
Keyes, KM
Wall, MM
Aharonovich, E
Aivadyan, C
Greenstein, E
Spivak, B
Weizman, A
Frisch, A
Grant, BF
Hasin, D
AF Shmulewitz, Dvora
Keyes, Katherine M.
Wall, Melanie M.
Aharonovich, Efrat
Aivadyan, Christina
Greenstein, Eliana
Spivak, Baruch
Weizman, Abraham
Frisch, Amos
Grant, Bridget F.
Hasin, Deborah
TI Nicotine dependence, abuse and craving: dimensionality in an Israeli
sample
SO ADDICTION
LA English
DT Article
DE DSM-IV; DSM-5; Israel; item response theory; nicotine dependence;
nicotine use disorders
ID ALCOHOL-USE DISORDERS; ITEM RESPONSE THEORY; NATIONAL EPIDEMIOLOGIC
SURVEY; RECENT RUSSIAN IMMIGRANTS; GENERAL-POPULATION SAMPLE; DSM-IV;
DIAGNOSTIC-CRITERIA; DRINKING PATTERNS; UNITED-STATES; DRUG-ABUSE
AB Aims Evidence-based changes planned for Diagnostic and Statistical Manual 5th edition (DSM-5) substance use disorders (SUDs) include combining dependence and three of the abuse criteria into one disorder and adding a criterion indicating craving. Because DSM-IV did not include a category for nicotine abuse, little empirical support is available for aligning the nicotine use disorder criteria with the DSM-5 criteria for other SUDs. Design Latent variable analyses, bootstrap tests and likelihood ratio tests were used to explore the unidimensionality, psychometric properties and information of the nicotine criteria. Setting and participants A sample of household residents selected from the Israeli population register yielded 727 life-time cigarette smokers. Measurements DSM-IV nicotine dependence criteria and proposed abuse and craving criteria, assessed with a structured interview. Findings Three abuse criteria (hazardous use, social/interpersonal problems and neglect roles) were prevalent among smokers, formed a unidimensional latent trait with nicotine dependence criteria, were intermixed with dependence criteria across the severity spectrum and significantly increased the diagnostic information over the dependence-only model. A craving criterion was shown to fit well with the other criteria. Conclusion Similar to findings from research on other substances, nicotine dependence, abuse and craving criteria appear to derive from a common underlying dimension. The results support alignment of nicotine criteria with those for alcohol and drug use disorders in Diagnostic and Statistical Manual 5th edition.
C1 [Shmulewitz, Dvora; Wall, Melanie M.; Aharonovich, Efrat; Hasin, Deborah] Columbia Univ, Dept Psychiat, Coll Phys & Surg, New York, NY 10032 USA.
[Shmulewitz, Dvora; Keyes, Katherine M.; Wall, Melanie M.; Aharonovich, Efrat; Aivadyan, Christina; Greenstein, Eliana; Hasin, Deborah] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Keyes, Katherine M.; Hasin, Deborah] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA.
[Wall, Melanie M.] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY 10032 USA.
[Spivak, Baruch; Weizman, Abraham; Frisch, Amos] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel.
[Weizman, Abraham; Frisch, Amos] Felsenstein Med Res Ctr, Petah Tiqwa, Israel.
[Weizman, Abraham] Geha Mental Hlth Ctr, Res Unit, Petah Tiqwa, Israel.
[Grant, Bridget F.] Natl Inst Alcohol Abuse & Alcoholism, Lab Epidemiol & Biometry, Bethesda, MD USA.
RP Hasin, D (reprint author), Columbia Univ, Dept Psychiat, Coll Phys & Surg, 1051 Riverside Dr 123, New York, NY 10032 USA.
EM dsh2@columbia.edu
FU National Institutes of Health [R01AA013654, R01DA018652, K05AA014223,
F31DA026689, K23DA016743]; New York State Psychiatric Institute
FX This research was funded by National Institutes of Health grants
R01AA013654, R01DA018652, K05AA014223 (Hasin), F31DA026689 (Keyes),
K23DA016743 (Aharonovich) and the New York State Psychiatric Institute
(Hasin). We would like to acknowledge the helpful consultations of
Rachel Bar-Hamburger PhD, Rina Meyer and Zalman Shoval in collecting the
data in Israel, and extensive input from the DSM-5 Substance Disorders
Work-group, who reviewed and approved the questions included in the
analyses, and discussed earlier versions of the analyses and text in a
series of conference calls.
NR 67
TC 13
Z9 13
U1 6
U2 11
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0965-2140
J9 ADDICTION
JI Addiction
PD SEP
PY 2011
VL 106
IS 9
BP 1675
EP 1686
DI 10.1111/j.1360-0443.2011.03484.x
PG 12
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 803YP
UT WOS:000293619300022
PM 21545668
ER
PT J
AU Dawson, DA
AF Dawson, Deborah A.
TI RISKY SINGLE-OCCASION DRINKING
SO ADDICTION
LA English
DT Letter
C1 NIAAA, NIH, Bethesda, MD USA.
RP Dawson, DA (reprint author), NIAAA, NIH, Bethesda, MD USA.
EM ddawson@willco.niaaa.nih.gov
NR 2
TC 0
Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0965-2140
J9 ADDICTION
JI Addiction
PD SEP
PY 2011
VL 106
IS 9
BP 1709
EP 1710
DI 10.1111/j.1360-0443.2011.03530.x
PG 3
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 803YP
UT WOS:000293619300028
PM 21714824
ER
PT J
AU Sanders-Beer, BE
Hirsch, VM
AF Sanders-Beer, B. E.
Hirsch, V. M.
TI EVOLUTIONARY HISTORY OF PRIMATE LENTIVIRUSES IN OLD WORLD MONKEYS
(CERCOPITHECIDAE)
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Meeting Abstract
CT 34th Annual Meeting of the American-Society-of-Primatologists
CY SEP 16-19, 2011
CL Austin, TX
SP Amer Soc Primatol
C1 [Sanders-Beer, B. E.] BIOQUAL Inc, Rockville, MD 20850 USA.
[Hirsch, V. M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0275-2565
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD SEP
PY 2011
VL 73
SU 1
MA 48
BP 46
EP 46
PG 1
WC Zoology
SC Zoology
GA 805XO
UT WOS:000293764600043
ER
PT J
AU Hipps, A
Maxwell, WF
Page, H
Suomi, SJ
Barr, CS
Schwandt, ML
Higley, JD
AF Hipps, A.
Maxwell, W. F.
Page, H.
Suomi, S. J.
Barr, C. S.
Schwandt, M. L.
Higley, J. D.
TI EFFECT OF SOCIAL SEPARATION ON MOTHER-DAUGHTER RELATIONSHIPS IN INFANT
RHESUS MACAQUES
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Meeting Abstract
CT 34th Annual Meeting of the American-Society-of-Primatologists
CY SEP 16-19, 2011
CL Austin, TX
SP Amer Soc Primatol
C1 [Hipps, A.; Maxwell, W. F.; Page, H.; Higley, J. D.] Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA.
[Barr, C. S.; Schwandt, M. L.] NIAAA, NIH, LCS, Bethesda, MD USA.
[Suomi, S. J.] NICHD, NIH, LCE, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0275-2565
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD SEP
PY 2011
VL 73
SU 1
MA 92
BP 61
EP 61
PG 1
WC Zoology
SC Zoology
GA 805XO
UT WOS:000293764600087
ER
PT J
AU Jensen, MB
Chaffin, AC
Barr, CS
Schwandt, ML
Suomi, SJ
Higley, JD
AF Jensen, M. B.
Chaffin, A. C.
Barr, C. S.
Schwandt, M. L.
Suomi, S. J.
Higley, J. D.
TI MOTHER-INFANT SEPARATION IS ASSOCIATED WITH LATER PATHOLOGICAL BEHAVIORS
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Meeting Abstract
CT 34th Annual Meeting of the American-Society-of-Primatologists
CY SEP 16-19, 2011
CL Austin, TX
SP Amer Soc Primatol
C1 [Jensen, M. B.; Chaffin, A. C.; Higley, J. D.] Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA.
[Barr, C. S.; Schwandt, M. L.; Suomi, S. J.] NICHD, NIH, Bethesda, MD USA.
[Barr, C. S.; Schwandt, M. L.; Suomi, S. J.] NIAAA, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0275-2565
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD SEP
PY 2011
VL 73
SU 1
MA 94
BP 62
EP 62
PG 1
WC Zoology
SC Zoology
GA 805XO
UT WOS:000293764600089
ER
PT J
AU Paukner, A
Suomi, SJ
AF Paukner, A.
Suomi, S. J.
TI FUR RUBBING AFFECTS SUBSEQUENT SOCIAL BEHAVIOR IN CAPTIVE CAPUCHIN
MONKEYS (CEBUS APELLA)
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Meeting Abstract
CT 34th Annual Meeting of the American-Society-of-Primatologists
CY SEP 16-19, 2011
CL Austin, TX
SP Amer Soc Primatol
C1 [Paukner, A.; Suomi, S. J.] NIH Anim Ctr, Comparat Ethol Lab, Poolesville, MD 20837 USA.
NR 0
TC 0
Z9 0
U1 1
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0275-2565
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD SEP
PY 2011
VL 73
SU 1
MA 108
BP 66
EP 66
PG 1
WC Zoology
SC Zoology
GA 805XO
UT WOS:000293764600103
ER
PT J
AU Bower, S
Ferrari, PF
Vanderwert, R
Paukner, A
Suomi, SJ
Fox, NA
AF Bower, S.
Ferrari, P. F.
Vanderwert, R.
Paukner, A.
Suomi, S. J.
Fox, N. A.
TI NEUROPHYSIOLOGICAL EVIDENCE FOR A MIRROR NEURON SYSTEM IN NEWBORN RHESUS
MACAQUES
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Meeting Abstract
CT 34th Annual Meeting of the American-Society-of-Primatologists
CY SEP 16-19, 2011
CL Austin, TX
SP Amer Soc Primatol
C1 [Bower, S.; Paukner, A.; Suomi, S. J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, NIH Anim Ctr, Dickerson, MD 20842 USA.
[Ferrari, P. F.] Univ Parma, Dipartimento Biol Evolut & Funz, I-43100 Parma, Italy.
[Ferrari, P. F.] Univ Parma, Dipartimento Neurosci, I-43100 Parma, Italy.
[Ferrari, P. F.] Italian Inst Technol, IIT, Parma, Italy.
[Vanderwert, R.; Fox, N. A.] Univ Maryland, Dept Human Dev, College Pk, MD 20742 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0275-2565
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD SEP
PY 2011
VL 73
SU 1
MA 178
BP 91
EP 91
PG 1
WC Zoology
SC Zoology
GA 805XO
UT WOS:000293764600179
ER
PT J
AU Chaffin, AC
Blocker, DJ
Barr, C
Schwandt, ML
Chefer, S
Stein, E
Suomi, SJ
Higley, JD
AF Chaffin, A. C.
Blocker, D. J.
Barr, C.
Schwandt, M. L.
Chefer, S.
Stein, E.
Suomi, S. J.
Higley, J. D.
TI BRAIN STRUCTURES ASSOCIATED WITH TEMPERAMENT AND SOCIAL BEHAVIOR IN
RHESUS MONKEYS
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Meeting Abstract
CT 34th Annual Meeting of the American-Society-of-Primatologists
CY SEP 16-19, 2011
CL Austin, TX
SP Amer Soc Primatol
C1 [Chaffin, A. C.; Blocker, D. J.; Higley, J. D.] Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA.
[Barr, C.; Schwandt, M. L.; Chefer, S.; Stein, E.; Suomi, S. J.] NICHD, NIH, NIAAA, Bethesda, MD USA.
[Barr, C.; Schwandt, M. L.; Chefer, S.; Stein, E.; Suomi, S. J.] NIDA, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0275-2565
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD SEP
PY 2011
VL 73
SU 1
MA 179
BP 92
EP 92
PG 1
WC Zoology
SC Zoology
GA 805XO
UT WOS:000293764600180
ER
PT J
AU Orgad, K
Gibson, MS
Chaffin, AC
Suomi, SJ
Barr, CS
Schwandt, ML
Higley, JD
AF Orgad, K.
Gibson, M. S.
Chaffin, A. C.
Suomi, S. J.
Barr, C. S.
Schwandt, M. L.
Higley, J. D.
TI EARLY TEMPERAMENT PREDICTS ALCOHOL INTAKE IN GROUP-HOUSED RHESUS
MACAQUES
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Meeting Abstract
CT 34th Annual Meeting of the American-Society-of-Primatologists
CY SEP 16-19, 2011
CL Austin, TX
SP Amer Soc Primatol
C1 [Orgad, K.; Gibson, M. S.; Chaffin, A. C.; Higley, J. D.] Brigham Young Univ, Dept Psychol & Neurosci, Provo, UT 84602 USA.
[Barr, C. S.; Schwandt, M. L.] NIAAA, NIH Anim Ctr, LCTS, Bethesda, MD USA.
[Suomi, S. J.] NICHD, NIH Anim Ctr, LCE, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0275-2565
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD SEP
PY 2011
VL 73
SU 1
MA 180
BP 92
EP 92
PG 1
WC Zoology
SC Zoology
GA 805XO
UT WOS:000293764600181
ER
PT J
AU Suarez-Jimenez, B
Hathaway, A
Waters, C
Vaughan, K
Suomi, SJ
Noble, P
Nelson, E
AF Suarez-Jimenez, B.
Hathaway, A.
Waters, C.
Vaughan, K.
Suomi, S. J.
Noble, P.
Nelson, E.
TI EFFECT OF MOTHER'S DOMINANCE RANK ON OFFSPRING TEMPERAMENT IN INFANT
RHESUS MONKEYS (MACACA MULATTA)
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Meeting Abstract
CT 34th Annual Meeting of the American-Society-of-Primatologists
CY SEP 16-19, 2011
CL Austin, TX
SP Amer Soc Primatol
C1 [Suarez-Jimenez, B.; Hathaway, A.; Waters, C.; Vaughan, K.; Noble, P.; Nelson, E.] NIMH, NIH, Bethesda, MD 20892 USA.
[Suomi, S. J.] NICHD, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0275-2565
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD SEP
PY 2011
VL 73
SU 1
MA 182
BP 93
EP 93
PG 1
WC Zoology
SC Zoology
GA 805XO
UT WOS:000293764600183
ER
PT J
AU Songrady, JC
Suomi, SJ
Egan, LC
Paukner, A
AF Songrady, J. C.
Suomi, S. J.
Egan, L. C.
Paukner, A.
TI THE EFFECTS OF EXTRINSIC REWARD ON INTRINSIC MOTIVATION IN INFANT RHESUS
MACAQUES (MACACA MULATTA)
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Meeting Abstract
CT 34th Annual Meeting of the American-Society-of-Primatologists
CY SEP 16-19, 2011
CL Austin, TX
SP Amer Soc Primatol
C1 [Songrady, J. C.; Suomi, S. J.; Paukner, A.] NIH, Anim Ctr, Dickerson, MD 20842 USA.
[Songrady, J. C.; Suomi, S. J.; Paukner, A.] NICHHD, Bethesda, MD USA.
[Egan, L. C.] Northwestern Univ, Kellogg Sch Management, Evanston, IL 60208 USA.
NR 0
TC 0
Z9 0
U1 1
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0275-2565
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD SEP
PY 2011
VL 73
SU 1
MA 188
BP 95
EP 95
PG 1
WC Zoology
SC Zoology
GA 805XO
UT WOS:000293764600189
ER
PT J
AU Pilkonis, PA
Choi, SW
Reise, SP
Stover, AM
Riley, WT
Cella, D
AF Pilkonis, Paul A.
Choi, Seung W.
Reise, Steven P.
Stover, Angela M.
Riley, William T.
Cella, David
CA PROMIS Cooperative Grp
TI Item Banks for Measuring Emotional Distress From the Patient-Reported
Outcomes Measurement Information System (PROMIS (R)): Depression,
Anxiety, and Anger
SO ASSESSMENT
LA English
DT Article
DE depression; anxiety; anger; item response theory; measurement
ID COMPUTERIZED ADAPTIVE ASSESSMENT; QUALITY-OF-LIFE; RESPONSE THEORY;
TRIPARTITE MODEL; SHORT-FORMS; BIFACTOR ANALYSIS; SYMPTOM STRUCTURE;
MENTAL-DISORDERS; BECK DEPRESSION; MOOD DISORDERS
AB The authors report on the development and calibration of item banks for depression, anxiety, and anger as part of the Patient-Reported Outcomes Measurement Information System (PROMIS (R)). Comprehensive literature searches yielded an initial bank of 1,404 items from 305 instruments. After qualitative item analysis (including focus groups and cognitive interviewing), 168 items (56 for each construct) were written in a first person, past tense format with a 7-day time frame and five response options reflecting frequency. The calibration sample included nearly 15,000 respondents. Final banks of 28, 29, and 29 items were calibrated for depression, anxiety, and anger, respectively, using item response theory. Test information curves showed that the PROMIS item banks provided more information than conventional measures in a range of severity from approximately -1 to +3 standard deviations (with higher scores indicating greater distress). Short forms consisting of seven to eight items provided information comparable to legacy measures containing more items.
C1 [Pilkonis, Paul A.; Stover, Angela M.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
[Choi, Seung W.; Cella, David] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Reise, Steven P.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Riley, William T.] NHLBI, Bethesda, MD 20892 USA.
RP Pilkonis, PA (reprint author), Western Psychiat Inst & Clin, 3811 OHara St, Pittsburgh, PA USA.
EM pilkonispa@upmc.edu
FU NCATS NIH HHS [UL1 TR000005]; NIAMS NIH HHS [U01AR52171, U01 AR052155,
U01 AR052155-06, U01 AR052158, U01 AR052170, U01 AR052171, U01 AR052177,
U01 AR052181, U01 AR052186, U01AR52155, U01AR52158, U01AR52170,
U01AR52177, U01AR52181, U01AR52186]
NR 110
TC 189
Z9 189
U1 12
U2 25
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1073-1911
J9 ASSESSMENT
JI Assessment
PD SEP
PY 2011
VL 18
IS 3
BP 263
EP 283
DI 10.1177/1073191111411667
PG 21
WC Psychology, Clinical
SC Psychology
GA 804AF
UT WOS:000293624700001
PM 21697139
ER
PT J
AU Wang, YY
Xiang, J
Vannest, J
Holroyd, T
Narmoneva, D
Horn, P
Liu, YH
Rose, D
deGrauw, T
Holland, S
AF Wang, Yingying
Xiang, Jing
Vannest, Jennifer
Holroyd, Tom
Narmoneva, Daria
Horn, Paul
Liu, Yinhong
Rose, Douglas
deGrauw, Ton
Holland, Scott
TI Neuromagnetic measures of word processing in bilinguals and monolinguals
SO CLINICAL NEUROPHYSIOLOGY
LA English
DT Article
DE Magnetoencephalography; Word processing; Bilinguals; Monolinguals;
Frequency; Oscillation
ID 2ND-LANGUAGE LEARNERS; FREQUENCY DIFFERENCES; CEREBRAL ASYMMETRY;
LEXICAL DECISION; BRAIN ACTIVITY; LANGUAGE; CHINESE; OSCILLATIONS;
ENGLISH; MAGNETOENCEPHALOGRAPHY
AB Objective: This study aimed to use magnetoencephalography (MEG) to examine the question of whether Mandarin-English bilingual speakers recruit the same cortical areas or develop distinct language-specific networks without overlaps for word processing.
Methods: Eight healthy Mandarin-English bilingual adults and eight healthy English monolingual adults were scanned while single-word paradigms were audio-visually presented.
Results: Our results showed significantly stronger beta-band power suppression in the right inferior parietal lobe (IPL) covering the supramarginal gyrus (BA 40) and angular gyrus (BA 39) for bilinguals when processing Mandarin versus English. Moreover, there were no significant differences between bilinguals and monolinguals in the left inferior frontal cortex (LIFC, BA 44/45) when both were processing their first language.
Conclusions: These results support the view that Mandarin-English bilinguals have a shared neural system for word processing in both the first and second language, which is highly similar to monolinguals', but with stronger right hemisphere involvement.
Significance: To our knowledge, this is the first MEG study to investigate the spatio-temporal and frequency characteristics between bilinguals and monolinguals, which provides us a new angle to better understand the language system in bilinguals' and monolingual's brain. (C) 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
C1 [Wang, Yingying; Narmoneva, Daria] Univ Cincinnati, Dept Biomed Engn, Cincinnati, OH USA.
[Wang, Yingying; Xiang, Jing; Vannest, Jennifer; Horn, Paul; Rose, Douglas; deGrauw, Ton] Cincinnati Childrens Hosp Med Ctr, Div Neurol, Cincinnati, OH USA.
[Wang, Yingying; Vannest, Jennifer; Holland, Scott] Cincinnati Childrens Hosp Res Fdn, Pediat Neuroimaging Res Consortium, Cincinnati, OH USA.
[Holroyd, Tom] NIMH, MEG Core Facil, Bethesda, MD 20892 USA.
[Horn, Paul] Univ Cincinnati, Dept Math Sci, Cincinnati, OH 45221 USA.
[Liu, Yinhong] Beijing Hosp, Minist Hlth, Dept Neurol, Beijing, Peoples R China.
RP Wang, YY (reprint author), MLC 5033,3333 Burnet Ave, Cincinnati, OH 45229 USA.
EM yingying.wang@cchmc.org
RI Wang, Yingying/A-4694-2011;
OI Holland, Scott/0000-0003-3719-0875
FU Cincinnati Children's Hospital Medical Centre, Cincinnati, OH, USA
FX This study was supported by a Trustee Grant to Dr. Jing Xiang from
Cincinnati Children's Hospital Medical Centre, Cincinnati, OH, USA. We
would like to thank Dr. David Brown for his help in audio recording and
Ms. Akhila Rajagopal for her help in statistical analysis. Also we would
like to thank Mr. Kendall O'Brien for his technical help in performing
all the MRI scans.
NR 66
TC 11
Z9 11
U1 3
U2 12
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 2011
VL 122
IS 9
BP 1706
EP 1717
DI 10.1016/j.clinph.2011.02.008
PG 12
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 799EU
UT WOS:000293267800005
PM 21414839
ER
PT J
AU Angerer, LM
Yaguchi, S
Angerer, RC
Burke, RD
AF Angerer, Lynne M.
Yaguchi, Shunsuke
Angerer, Robert C.
Burke, Robert D.
TI The evolution of nervous system patterning: insights from sea urchin
development
SO DEVELOPMENT
LA English
DT Review
DE Wnt; TGF beta; Nodal; BMP; Dorsal-ventral axis; Anterior-posterior axis;
Lefty; Chordin; Six3; FoxQ2; Ciliary band; Apical organ; Ectoderm
patterning; Neural development; Neural patterning
ID ORAL-ABORAL AXIS; NUCLEAR BETA-CATENIN; EMBRYONIC STEM-CELLS;
ANIMAL-VEGETAL AXIS; STRONGYLOCENTROTUS-PURPURATUS; NEURAL INDUCTION;
GENE NETWORK; REGULATORY ANALYSIS; FATE SPECIFICATION; MESODERM
INDUCTION
AB Recent studies of the sea urchin embryo have elucidated the mechanisms that localize and pattern its nervous system. These studies have revealed the presence of two overlapping regions of neurogenic potential at the beginning of embryogenesis, each of which becomes progressively restricted by separate, yet linked, signals, including Wnt and subsequently Nodal and BMP. These signals act to specify and localize the embryonic neural fields - the anterior neuroectoderm and the more posterior ciliary band neuroectoderm - during development. Here, we review these conserved nervous system patterning signals and consider how the relationships between them might have changed during deuterostome evolution.
C1 [Angerer, Lynne M.; Angerer, Robert C.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA.
[Yaguchi, Shunsuke] Univ Tsukuba, Shimoda Marine Res Ctr, Shimoda 4150025, Japan.
[Burke, Robert D.] Univ Victoria, Biochem Microbiol Dept, Victoria, BC V3P 5C2, Canada.
RP Angerer, LM (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA.
EM langerer@mail.nih.gov
OI Yaguchi, Shunsuke/0000-0002-8326-5762; Burke, Robert/0000-0001-5527-4410
FU Division of Intramural Research in the National Institute for Dental and
Craniofacial Research, National Institutes of Health; Ministry of
Education, Culture, Sports, Science and Technology of the Japanese
Government (MEXT); NSERC
FX We thank Adi Sethi, Diane Adams and Ryan Range for discussions and
especially Zheng Wei for experimental and bioinformatic contributions.
Support for this work was provided by the Division of Intramural
Research in the National Institute for Dental and Craniofacial Research,
National Institutes of Health (L.M.A. and R.C.A.), Special Coordination
Funds for Promoting Science and Technology of the Ministry of Education,
Culture, Sports, Science and Technology of the Japanese Government
(MEXT), by a Grant-in Aid for Young Scientists (Start-up) (S.Y.) and
NSERC (R.D.B.). Deposited in PMC for release after 12 months.
NR 105
TC 44
Z9 44
U1 3
U2 35
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0950-1991
J9 DEVELOPMENT
JI Development
PD SEP 1
PY 2011
VL 138
IS 17
BP 3613
EP 3623
DI 10.1242/dev.058172
PG 11
WC Developmental Biology
SC Developmental Biology
GA 804XG
UT WOS:000293687700002
PM 21828090
ER
PT J
AU Lim, AH
Suli, A
Yaniv, K
Weinstein, B
Li, DY
Chien, CB
AF Lim, Amy H.
Suli, Arminda
Yaniv, Karina
Weinstein, Brant
Li, Dean Y.
Chien, Chi-Bin
TI Motoneurons are essential for vascular pathfinding
SO DEVELOPMENT
LA English
DT Article
DE Netrin; DCC; Lymphatic; Parachordal chain; Motoneuron; Axon guidance;
Vascular guidance; Angiogenesis; Zebrafish
ID INHIBITS SPROUTING ANGIOGENESIS; NETRIN RECEPTOR; ZEBRAFISH EMBRYO;
IN-VIVO; LYMPHATIC DEVELOPMENT; GUIDANCE CUES; AXON GUIDANCE; UNC5B;
DCC; EXPRESSION
AB The neural and vascular systems share common guidance cues that have direct and independent signaling effects on nerves and endothelial cells. Here, we show that zebrafish Netrin 1a directs Dcc-mediated axon guidance of motoneurons and that this neural guidance function is essential for lymphangiogenesis. Specifically, Netrin 1a secreted by the muscle pioneers at the horizontal myoseptum (HMS) is required for the sprouting of dcc-expressing rostral primary motoneuron (RoP) axons and neighboring axons along the HMS, adjacent to the future trajectory of the parachordal chain (PAC). These axons are required for the formation of the PAC and, subsequently, the thoracic duct. The failure to form the PAC in netrin 1a or dcc morphants is phenocopied by laser ablation of motoneurons and is rescued both by cellular transplants and overexpression of dcc mRNA. These results provide a definitive example of the requirement of axons in endothelial guidance leading to the parallel patterning of nerves and vessels in vivo.
C1 [Lim, Amy H.; Li, Dean Y.] Univ Utah, Program Mol Med, Salt Lake City, UT 84112 USA.
[Lim, Amy H.; Suli, Arminda; Chien, Chi-Bin] Univ Utah, Dept Neurobiol & Anat, Salt Lake City, UT 84132 USA.
[Yaniv, Karina] Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel.
[Weinstein, Brant] NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA.
[Li, Dean Y.] Univ Utah, Dept Med, Div Cardiol, Salt Lake City, UT 84132 USA.
[Li, Dean Y.] Univ Utah, Dept Oncol Sci, Salt Lake City, UT 84112 USA.
RP Li, DY (reprint author), Univ Utah, Program Mol Med, 15 N 2030 East,Room 4140, Salt Lake City, UT 84112 USA.
EM dean.li@u2m2.utah.edu
OI Suli, Arminda/0000-0003-2690-8407
FU NHLBI; NIH (NICHD)
FX We thank D. Lim for graphical assistance; Hideo Otsuna for help with
FluoRender; K. Thomas, F. Poulain, N. London, K. Kwan and A. Chan for
critical reading of this manuscript; S. Hutchinson, L. Hale and J. Eisen
for helpful discussions; G. King and the Centralized Zebrafish Animal
Resource Facility; C. Rodesch, K. Carney and the Cell Imaging Core;
Xiaoming Sheng at the Biostatistics Core for help with statistical
analysis; M. Granato, J. Yost and N. Lawson for fish; L. Hale and J.
Eisen for isl1 morpholinos; B. Appel for olig2 morpholino; Uwe Strahle
for a partial netrin 1a clone; and M. Jurynec and D. Grunwald for the
4D9 antibody and cyclopamine. Funding: D.Y.L. and C.-B.C., NHLBI; B.W.,
Intramural Research Program of the NIH (NICHD). Deposited in PMC for
release after 12 months.
NR 58
TC 24
Z9 24
U1 0
U2 5
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0950-1991
J9 DEVELOPMENT
JI Development
PD SEP 1
PY 2011
VL 138
IS 17
BP 3847
EP 3857
DI 10.1242/dev.068403
PG 11
WC Developmental Biology
SC Developmental Biology
GA 804XG
UT WOS:000293687700023
PM 21828101
ER
PT J
AU Lauer, MS
Hodes, R
AF Lauer, Michael S.
Hodes, Richard
TI Epidemiology, Comparative Effectiveness Research, and the National
Institutes of Health Forces for Health
SO EPIDEMIOLOGY
LA English
DT Editorial Material
ID CORONARY HEART-DISEASE; IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; TYPE-2
DIABETES-MELLITUS; OUTCOMES; PREVENTION; MORTALITY; TRIAL; RISK;
INTERVENTION; PROGRAM
C1 [Lauer, Michael S.] NHLBI, Off Director, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
[Hodes, Richard] NIA, Off Director, NIH, Bethesda, MD 20892 USA.
RP Lauer, MS (reprint author), 6701 Rockledge Dr,Room 8128, Bethesda, MD 20892 USA.
EM lauerm@nhlbi.nih.gov
RI Lauer, Michael/L-9656-2013
OI Lauer, Michael/0000-0002-9217-8177
FU Intramural NIH HHS [Z99 HL999999]
NR 25
TC 3
Z9 4
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1044-3983
EI 1531-5487
J9 EPIDEMIOLOGY
JI Epidemiology
PD SEP
PY 2011
VL 22
IS 5
BP 625
EP 628
DI 10.1097/EDE.0b013e3182262ac6
PG 4
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 801NT
UT WOS:000293447500005
PM 21811109
ER
PT J
AU Saha-Chaudhuri, P
Umbach, DM
Weinberg, CR
AF Saha-Chaudhuri, Paramita
Umbach, David M.
Weinberg, Clarice R.
TI Pooled Exposure Assessment for Matched Case-control Studies
SO EPIDEMIOLOGY
LA English
DT Article
ID POPULATIONS; BIOMARKERS; COHORTS; BLOOD; SERA; RISK
AB Exposure assessment using biologic specimens is important for epidemiology but may become impracticable if assays are expensive, specimen volumes are marginally adequate, or analyte levels fall below the limit of detection. Pooled exposure assessment can provide an effective remedy for these problems in unmatched case-control studies. We extend pooled exposure strategies to handle specimens collected in a matched case-control study. We show that if a logistic model applies to individuals, then a logistic model also applies to an analysis using pooled exposures. Consequently, the individual-level odds ratio can be estimated while conserving both cost and specimen. We discuss appropriate pooling strategies for a single exposure, with adjustment for multiple, possibly continuous, covariates (confounders) and assessment of effect modification by a categorical variable. We assess the performance of the approach via simulations and conclude that pooled strategies can markedly improve efficiency for matched as well as unmatched case-control studies. (Epidemiology 2011; 22: 704-712)
C1 [Saha-Chaudhuri, Paramita; Umbach, David M.; Weinberg, Clarice R.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA.
RP Saha-Chaudhuri, P (reprint author), NIEHS, Biostat Branch, POB 12233,Mail Drop A3-03,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM sahap@niehs.nih.gov
RI Saha Chaudhuri, Paramita/F-3835-2010;
OI Saha Chaudhuri, Paramita/0000-0003-1987-320X
FU NIH, National Institute of Environmental Health Sciences [ES040006-14]
FX Supported by the Intramural Research Program of the NIH, National
Institute of Environmental Health Sciences (project ES040006-14).
NR 20
TC 6
Z9 6
U1 0
U2 4
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 2011
VL 22
IS 5
BP 704
EP 712
DI 10.1097/EDE.0b013e318227af1a
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 801NT
UT WOS:000293447500016
PM 21747285
ER
PT J
AU Schoonjans, F
De Bacquer, D
Schmid, P
AF Schoonjans, Frank
De Bacquer, Dirk
Schmid, Pirmin
TI Estimation of Population Percentiles
SO EPIDEMIOLOGY
LA English
DT Letter
C1 [Schoonjans, Frank] Ghent Univ Hosp, Dept Endocrinol, B-9000 Ghent, Belgium.
[Schoonjans, Frank] MedCalc Software Bvba, Mariakerke, Belgium.
[De Bacquer, Dirk] Univ Ghent, Dept Publ Hlth, B-9000 Ghent, Belgium.
[Schmid, Pirmin] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Schoonjans, F (reprint author), Ghent Univ Hosp, Dept Endocrinol, B-9000 Ghent, Belgium.
EM frank.schoonjans@ugent.be
FU Intramural NIH HHS [Z99 CL999999]
NR 6
TC 8
Z9 9
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD SEP
PY 2011
VL 22
IS 5
BP 750
EP 751
DI 10.1097/EDE.0b013e318225c1de
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 801NT
UT WOS:000293447500027
PM 21811118
ER
PT J
AU Noureddin, M
Kleiner, DE
Gharib, AM
Bratslavsky, G
Heller, T
AF Noureddin, Mazen
Kleiner, David E.
Gharib, Ahmed M.
Bratslavsky, Gennady
Heller, Theo
TI To resect or not to resect? That is the question
SO GUT
LA English
DT Editorial Material
ID LIVER
C1 [Noureddin, Mazen; Heller, Theo] NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20892 USA.
[Kleiner, David E.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Gharib, Ahmed M.] NIDDK, Integrat Cardiovasc Imaging Sect, NIH, Bethesda, MD 20892 USA.
[Bratslavsky, Gennady] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Noureddin, M (reprint author), NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20892 USA.
EM noureddinm@niddk.nih.gov
RI Gharib, Ahmed/O-2629-2016;
OI Gharib, Ahmed/0000-0002-2476-481X; Kleiner, David/0000-0003-3442-4453
FU Intramural NIH HHS [Z99 DK999999, ZIA DK075083-01]
NR 4
TC 0
Z9 0
U1 0
U2 0
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0017-5749
J9 GUT
JI Gut
PD SEP
PY 2011
VL 60
IS 9
BP 1177
EP +
DI 10.1136/gut.2010.221440
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 803NS
UT WOS:000293588600005
PM 20965874
ER
PT J
AU Vogel-Claussen, J
Shehata, ML
Lossnitzer, D
Skrok, J
Singh, S
Boyce, D
Lechtzin, N
Girgis, RE
Mathai, SC
Lima, JA
Bluemke, DA
Hassoun, PM
AF Vogel-Claussen, Jens
Shehata, Monda L.
Lossnitzer, Dirk
Skrok, Jan
Singh, Sukhminder
Boyce, Danielle
Lechtzin, Noah
Girgis, Reda E.
Mathai, Stephen C.
Lima, Joao A.
Bluemke, David A.
Hassoun, Paul M.
TI Increased Right Ventricular Septomarginal Trabeculation Mass is a Novel
Marker for Pulmonary Hypertension Comparison With Ventricular Mass Index
and Right Ventricular Mass
SO INVESTIGATIVE RADIOLOGY
LA English
DT Article
DE cardiac MRI; pulmonary hypertension; ventricular mass index; right
ventricular septomarginal trabeculation
ID CARDIOVASCULAR MAGNETIC-RESONANCE; ARTERIAL-HYPERTENSION; CLINICAL
CLASSIFICATION; DOPPLER ULTRASOUND; PRESSURE; REGURGITATION;
EPIDEMIOLOGY; EXPERIENCE; ACCURACY; SURVIVAL
AB Objective: To prospectively evaluate the cardiac magnetic resonance (MR) imaging-derived measurement of right ventricular (RV) septomarginal trabeculation (SMT) mass as a noninvasive marker for pulmonary hypertension (PH), compared with the ventricular mass index (VMI = RV mass/left ventricular mass) and RV mass.
Materials and Methods: A total of 49 patients (60 +/- 12 years; 35 female) with suspected PH underwent cardiac MR and right heart catheterization on the same day. Eighteen normal volunteers were also included. The performance of SMT mass, VMI and RV mass measurement, with regard to PH detection, was analyzed using receiver operating characteristic curves. Logistic regression analysis was used to assess the association between SMT mass, RV mass, VMI, and PH.
Results: The area under the receiver operating characteristic curve for SMT mass/body surface area (BSA), VMI, and RV mass/BSA in diagnosing the presence or absence of PH was 0.88, 0.87, and 0.73 respectively. In multivariable models, both SMT mass/BSA (P = 0.005, odds ratio: 8.6) and VMI (P = 0. 012, odds ratio: 1.1) were found to be significant, independent predictors of PH.
Conclusion: Compared with right heart catheterization measurement, SMT mass and VMI are reproducible and noninvasive MR imaging markers for the diagnosis of PH.
C1 [Vogel-Claussen, Jens; Shehata, Monda L.; Skrok, Jan] Johns Hopkins Univ, Dept Radiol, Sch Med, Baltimore, MD 21287 USA.
[Vogel-Claussen, Jens] Univ Tubingen Hosp, Dept Diagnost & Intervent Radiol, Tubingen, Germany.
[Vogel-Claussen, Jens] Hannover Med Sch, Dept Radiol, D-3000 Hannover, Germany.
[Lossnitzer, Dirk] Univ Heidelberg Hosp, Dept Cardiol, Heidelberg, Germany.
[Singh, Sukhminder; Boyce, Danielle; Lechtzin, Noah; Girgis, Reda E.; Mathai, Stephen C.; Hassoun, Paul M.] Johns Hopkins Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21287 USA.
[Lima, Joao A.] Johns Hopkins Univ, Div Cardiol, Sch Med, Baltimore, MD 21287 USA.
[Bluemke, David A.] Natl Inst Biomed Imaging & Biomed Engn, Dept Radiol & Imaging Sci, NIH, Bethesda, MD USA.
RP Vogel-Claussen, J (reprint author), Johns Hopkins Univ, Dept Radiol, Sch Med, Nelson Basement MRI 143,600 N Wolfe St, Baltimore, MD 21287 USA.
EM jclauss1@jhmi.edu
OI Bluemke, David/0000-0002-8323-8086
FU NIH [1P50HL08946]
FX NIH 1P50HL08946. DAB supported by the NIH intramural research program.
NR 29
TC 14
Z9 15
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0020-9996
J9 INVEST RADIOL
JI Invest. Radiol.
PD SEP
PY 2011
VL 46
IS 9
BP 567
EP 575
DI 10.1097/RLI.0b013e31821b7041
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 804XK
UT WOS:000293688200005
PM 21577127
ER
PT J
AU Condon, TP
Jacobs, P
Tai, B
Pintello, D
Miner, L
Elcano, JC
AF Condon, Timothy P.
Jacobs, Petra
Tai, Betty
Pintello, Denise
Miner, Lucinda
Elcano, Jennifer C.
TI Patient Relapse in the Context of Drug Abuse Treatment
SO JOURNAL OF ADDICTION MEDICINE
LA English
DT Editorial Material
DE addiction; discharge policies; drug abuse treatment; relapse
ID ADAPTIVE TREATMENT MODEL; FOLLOW-UP OUTCOMES; MAINTENANCE TREATMENT;
CONTROLLED-TRIAL; ALCOHOL DEPENDENCE; OPIOID DEPENDENCE;
SUBSTANCE-ABUSE; CHRONIC PAIN; METHADONE; RETENTION
AB How do addiction treatment programs integrate the expectation of relapse into drug abuse treatment? This article serves as a thought piece to pose questions rather than definitive solutions. It reflects a distillation of discussions that occurred at the National Institute on Drug Abuse meeting titled "Program Response to Patient Relapse," held on July 15, 2009, along with quantitative and qualitative information about the patterns and types of discharge policies, which factors influence them, and how the culture of drug abuse treatment and the personnel interact with this issue. Some existing data on the discharging of relapsed patients are identified. A program's response to relapse is usually guided by its setting (level of care), philosophy (abstinence vs risk behavior reduction), and associated patient behavior ("benign" vs program disruptive). Key questions examined in this context include the following: Can different discharge policies impact a patient's access to treatment, and what are the implications of incorporating a medical model of addiction into discharge policies?
C1 [Condon, Timothy P.; Jacobs, Petra; Tai, Betty; Pintello, Denise; Miner, Lucinda; Elcano, Jennifer C.] Natl Inst Drug Abuse, NIH, Bethesda, MD 20892 USA.
RP Elcano, JC (reprint author), Natl Inst Drug Abuse, NIH, 6001 Execut Blvd,Suite 5230,MSC 9591, Bethesda, MD 20892 USA.
EM elcanoj@nida.nih.gov
NR 36
TC 2
Z9 2
U1 2
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1932-0620
J9 J ADDICT MED
JI J. Addict. Med.
PD SEP
PY 2011
VL 5
IS 3
BP 157
EP 162
DI 10.1097/ADM.0b013e31820497ae
PG 6
WC Substance Abuse
SC Substance Abuse
GA 806ST
UT WOS:000293832500001
PM 21844830
ER
PT J
AU Kloner, RA
Longacre, LS
AF Kloner, Robert A.
Longacre, Lisa Schwartz
TI Introduction to Proceedings of the NHLBI Workshop: New Horizons in
Cardioprotection-A Focused Issue of Journal of Cardiovascular
Pharmacology and Therapeutics
SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Editorial Material
C1 [Kloner, Robert A.] Univ So Calif, Inst Heart, Keck Sch Med, Good Samaritan Hosp, Los Angeles, CA 90017 USA.
[Longacre, Lisa Schwartz] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Kloner, RA (reprint author), Univ So Calif, Inst Heart, Keck Sch Med, Good Samaritan Hosp, 1225 Wilshire Blvd, Los Angeles, CA 90017 USA.
EM rkloner@goodsam.org
RI Kloner, Robert/B-2971-2012
NR 0
TC 2
Z9 2
U1 0
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1074-2484
J9 J CARDIOVASC PHARM T
JI J. Cardiovasc. Pharmacol. Ther.
PD SEP-DEC
PY 2011
VL 16
IS 3-4
BP 222
EP 222
DI 10.1177/1074248411413547
PG 1
WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy
SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy
GA 803QJ
UT WOS:000293595500001
PM 21821519
ER
PT J
AU Kloner, RA
Longacre, LS
AF Kloner, Robert A.
Longacre, Lisa Schwartz
TI State of the Science of Cardioprotection: Challenges and
Opportunities-Proceedings of the 2010 NHLBI Workshop on Cardioprotection
SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article; Proceedings Paper
CT Workshop on New Horizons in Cardioprotection
CY SEP 20-21, 2010
CL Rockville, MD
DE acute myocardial infarction; cardioactive agents; experimental
cardiology; acute coronary syndromes; heart disease
ID ACUTE MYOCARDIAL-INFARCTION; PERCUTANEOUS CORONARY INTERVENTION;
ISCHEMIA-REPERFUSION; REGIONAL HYPOTHERMIA; SIZE; PROTECTION; ADENOSINE;
THERAPY; RABBIT; INJURY
AB The National Heart, Lung, and Blood Institute convened a Workshop on September 20-21, 2010, "New Horizons in Cardioprotection," to identify future research directions for cardioprotection against ischemia and reperfusion injury. Since the early 1970s, there has been evidence that the size of a myocardial infarction could be altered by various interventions. Early coronary artery reperfusion has been an intervention that consistently reduces myocardial infarct size in animal models as well as humans. Most cardiologists agree that the best way to treat acute ST-segment elevation myocardial infarction is to reperfuse the infarct artery as soon as possible and to keep the infarct artery patent. In general, stenting is superior to angioplasty, which is superior to thrombolysis. There is no accepted adjunctive therapy to acutely limit myocardial infarct size along with reperfusion that is routinely used in clinical practice. In the Kloner experimental laboratory, some adjunctive therapies have reproducibly limited infarct size (regional hypothermia, preconditioning, cariporide, combinations of the above, remote preconditioning, certain adenosine agonists, and late sodium current blockade). In clinical trials, a host of pharmacologic adjunctive therapies have failed to either reduce infarct size or improve clinical outcome. Potential reasons for the failure of these trials are discussed. However, some adjunctive therapies have shown promise in data subanalyses or subpopulations of clinical trials (adenosine, therapeutic hypothermia, and hyperoxemic reperfusion) or in small clinical trials (atrial natriuretic peptide, ischemic postconditioning, and cyclosporine, the mitochondrial permeability transition pore inhibitor). A recent clinical trial with remote conditioning induced by repetitive inflation of a brachial artery cuff begun prior to hospitalization showed promise in improving myocardial salvage and there are several reports in the cardiothoracic literature, suggesting that remote preconditioning protects hearts during surgery. Thus, in 2011, there is hope that applying some of the body's own conditioning mechanisms may provide protection against ischemic damage.
C1 [Kloner, Robert A.] Univ So Calif, Good Samaritan Hosp, Inst Heart, Los Angeles, CA 90017 USA.
[Longacre, Lisa Schwartz] NHLBI, Bethesda, MD 20892 USA.
RP Kloner, RA (reprint author), Univ So Calif, Good Samaritan Hosp, Inst Heart, 1225 Wilshire Blvd, Los Angeles, CA 90017 USA.
EM rkloner@goodsam.org
RI Kloner, Robert/B-2971-2012
NR 42
TC 31
Z9 31
U1 0
U2 4
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1074-2484
J9 J CARDIOVASC PHARM T
JI J. Cardiovasc. Pharmacol. Ther.
PD SEP-DEC
PY 2011
VL 16
IS 3-4
BP 223
EP 232
DI 10.1177/1074248411402501
PG 10
WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy
SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy
GA 803QJ
UT WOS:000293595500002
PM 21821520
ER
PT J
AU Sack, MN
Murphy, E
AF Sack, Michael N.
Murphy, Elizabeth
TI The Role of Comorbidities in Cardioprotection
SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article; Proceedings Paper
CT Workshop on New Horizons in Cardioprotection
CY SEP 20-21, 2010
CL Rockville, MD
DE metabolic syndrome; ischemia-reperfusion injury; heart disease
ID NITRIC-OXIDE SYNTHASE; DIABETES-MELLITUS; ISCHEMIA/REPERFUSION INJURY;
CALORIC RESTRICTION; INFARCT SIZE; TETRAHYDROBIOPTERIN BH4; ENDOTHELIAL
DYSFUNCTION; MYOCARDIAL-INFARCTION; ISCHEMIA-REPERFUSION; CONSCIOUS
RABBITS
AB Cardioprotective strategies such as pre- and postconditioning result in a robust reduction in infarct size in young, healthy male animals. However, there are data suggesting that the protection is diminished in animals with comorbidities such as hypertension, hypercholesterolemia, and diabetes. It is important to understand at a mechanistic level the reasons for these differences. The effects of sex and diseases need to be considered in design of cardioprotective interventions in animal studies and clinical trials.
C1 [Sack, Michael N.] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA.
[Murphy, Elizabeth] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
RP Murphy, E (reprint author), Bld 10,Room 8N202,10 Ctr Dr, Bethesda, MD 20892 USA.
EM Tish.Murphy@nih.hhs.gov
FU Intramural NIH HHS [ZIA HL006059-02, ZIA HL002065-04, ZIA HL002066-04,
ZIA HL005102-07]
NR 54
TC 14
Z9 14
U1 0
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1074-2484
J9 J CARDIOVASC PHARM T
JI J. Cardiovasc. Pharmacol. Ther.
PD SEP-DEC
PY 2011
VL 16
IS 3-4
BP 267
EP 272
DI 10.1177/1074248411408313
PG 6
WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy
SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy
GA 803QJ
UT WOS:000293595500009
PM 21821527
ER
PT J
AU Arai, AE
AF Arai, Andrew E.
TI Magnetic Resonance Imaging for Area at Risk, Myocardial Infarction, and
Myocardial Salvage
SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article; Proceedings Paper
CT Workshop on New Horizons in Cardioprotection
CY SEP 20-21, 2010
CL Rockville, MD
DE acute myocardial infarction; area at risk; myocardial salvage; magnetic
resonance imaging; ischemia
ID EMISSION-COMPUTED-TOMOGRAPHY; DELAYED CONTRAST-ENHANCEMENT; ISCHEMIC
CELL-DEATH; CORONARY INTERVENTION; WAVEFRONT PHENOMENON; IRREVERSIBLE
INJURY; T2 QUANTIFICATION; STIMULATED ECHOES; RELAXATION TIMES; EDEMA
AB Almost all published preclinical studies of cardioprotective agents include a measurement of area at risk, infarct size, and thus allow determination of myocardial salvage as an indicator of therapeutic benefit. Until recently, single-photon emission tomography (SPECT) imaging with injection of sestamibi prior to intervention was the only clinical method suitable for making similar assessments in patients. Over the past 5 years, a large number of articles have documented that magnetic resonance imaging (MRI) can noninvasively determine area at risk, infarct size, and myocardial salvage. While T2-weighted imaging has been the method used most commonly, precontrast T1-weighted images and early gadolinium enhancement (EGE) images can also determine the size of the area at risk. All 3 of these MRI methods detect the area at risk based on myocardial edema resulting from ischemia. Late gadolinium enhancement (LGE) images provide a well-accepted reference standard for infarct size in all of those methods. Finally, LGE images can also provide a single modality measure of myocardial salvage based on the "wave front" of myocardial injury associated with the progressively more severe damage associated with acute myocardial infarction (MI). Essentially, the LGE images can provide an endocardial-based snap shot of infarct size and salvaged myocardium is estimated as the viable myocardium within the circumferential extent of the infarct. Thus, the purpose of this review is to provide an overview of how MRI can determine the area at risk, infarct size, and thus measure myocardial salvage.
C1 NHLBI, Dept Hlth & Human Serv, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
RP Arai, AE (reprint author), NHLBI, Dept Hlth & Human Serv, Cardiovasc & Pulm Branch, NIH, Bldg 10,RM B1D416,MSC1061,10 Ctr Dr, Bethesda, MD 20892 USA.
EM araia@nih.gov
FU Intramural NIH HHS [ZIA HL006136-02, Z99 HL999999, ZIA HL006136-01];
NHLBI NIH HHS [Z01 HL004607-08]
NR 56
TC 20
Z9 20
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1074-2484
J9 J CARDIOVASC PHARM T
JI J. Cardiovasc. Pharmacol. Ther.
PD SEP-DEC
PY 2011
VL 16
IS 3-4
BP 313
EP 320
DI 10.1177/1074248411412378
PG 8
WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy
SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy
GA 803QJ
UT WOS:000293595500016
PM 21821534
ER
PT J
AU Becker, MR
Choi, YS
Millar, SE
Udey, MC
AF Becker, Maria R.
Choi, Yeon S.
Millar, Sarah E.
Udey, Mark C.
TI Wnt Signaling Influences the Development of Murine Epidermal Langerhans
Cells
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Article
ID HEMATOPOIETIC STEM-CELL; DENDRITIC CELLS; BETA-CATENIN; IN-VIVO; CONTACT
HYPERSENSITIVITY; E-CADHERIN; MICE; SKIN; DICKKOPF-1; INHIBITION
AB Langerhans cells (LCs) are distinct dendritic cells (DCs) that populate stratified squamous epithelia. Despite extensive studies, our understanding of LC development is incomplete. Transforming growth factor beta 1 (TGF beta 1) is required for LC development, but other epidermis-derived influences may also be important. Recently, EpCAM (CD326) has been identified as a cell surface protein discriminating LCs from Langerin(+) dermal DCs and other DCs in the skin. EpCAM is a known transcriptional target of the Wnt signaling pathway. We hypothesized that intraepidermal Wnt signaling might influence LC development. Addition of Wnt3A into cultures of bone-marrow-derived cells in combination with TGF beta 1, GM-CSF, and M-CSF resulted in increased (33%; P<0.05) accumulation of EpCAM(+) DCs. In contrast, addition of the Wnt antagonist dickkopf-related protein 1 (Dkk1) decreased the number of EpCAM(+) DCs (21%; P<0.05). We used K14-KRM1; K5-rtTA; tetO-Dkk1 triple-transgenic and K5-rtTA; tetO-Dkk1 double-transgenic mice to test the in vivo relevance of our in vitro findings. Feeding doxycycline to nursing mothers induced expression of Dkk1 in the skin of transgenic pups, causing an obvious hair phenotype. Expression of Dkk1 reduced LC proliferation (40%; P<0.01) on P7, decreased LC densities (26%; P<0.05) on P14, and decreased EpCAM expression intensities on LCs as well (33%). In aggregate, these data suggest that Wnt signaling in skin influences LC development.
C1 [Becker, Maria R.; Udey, Mark C.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Choi, Yeon S.; Millar, Sarah E.] Univ Penn, Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA.
RP Udey, MC (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 10,Room 12N238, Bethesda, MD 20892 USA.
EM udey@helix.nih.gov
FU Center for Cancer Research, National Cancer Institute, The National
Institutes of Health
FX We thank Dr William Telford for his advice and assistance with flow and
laser scanning cytometer-related experiments. We also thank Jay Linton,
Michael Lu, and Dr Sei-ichiro Motegi for advice and assistance with
other experimental procedures. This work was supported by the Intramural
Research Program, Center for Cancer Research, National Cancer Institute,
The National Institutes of Health encompasses the preceding items
(program, center, institute).
NR 45
TC 7
Z9 8
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD SEP
PY 2011
VL 131
IS 9
BP 1861
EP 1868
DI 10.1038/jid.jid2011.131
PG 8
WC Dermatology
SC Dermatology
GA 808BO
UT WOS:000293948600014
PM 21614016
ER
PT J
AU Camargos, ST
Gurgel-Giannetti, J
Lees, A
Hardy, J
Singleton, A
Cardoso, F
AF Camargos, S. T.
Gurgel-Giannetti, J.
Lees, A.
Hardy, J.
Singleton, A.
Cardoso, F.
TI Low prevalence of PANK2 mutations in Brazilian patients with early onset
generalised dystonia and basal ganglia abnormalities on MRI
SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
LA English
DT Letter
ID HALLERVORDEN-SPATZ-SYNDROME; THE-TIGER SIGN
C1 [Camargos, S. T.; Gurgel-Giannetti, J.; Cardoso, F.] Univ Fed Minas Gerais, Movement Disorders Clin, Belo Horizonte, MG, Brazil.
[Lees, A.; Hardy, J.] Reta Lila Weston Inst, London, England.
[Singleton, A.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
RP Cardoso, F (reprint author), Univ Fed Minas Gerais, Movement Disorders Clin, Ave Pasteur 89-1107, Belo Horizonte, MG, Brazil.
EM cardosofe@terra.com.br
RI Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009; Lees,
Andrew/A-6605-2009; Cardoso, Francisco/A-2285-2014; CAMARGOS,
SARAH/O-4670-2014
OI Cardoso, Francisco/0000-0003-0808-0116; CAMARGOS,
SARAH/0000-0001-9829-6783
FU Intramural NIH HHS [ZIA AG000932-08]; Medical Research Council
[G0701075]; NIA NIH HHS [Z01 AG000957]; Parkinson's UK [G-0907]
NR 5
TC 0
Z9 0
U1 0
U2 0
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-3050
J9 J NEUROL NEUROSUR PS
JI J. Neurol. Neurosurg. Psychiatry
PD SEP
PY 2011
VL 82
IS 9
BP 1059
EP +
DI 10.1136/jnnp.2009.200808
PG 2
WC Clinical Neurology; Psychiatry; Surgery
SC Neurosciences & Neurology; Psychiatry; Surgery
GA 803PN
UT WOS:000293593300056
PM 20551478
ER
PT J
AU Williams-Brown, MY
Salih, SM
Xu, X
Veenstra, TD
Saeed, M
Theiler, SK
Diaz-Arrastia, CR
Salama, SA
AF Williams-Brown, Marian Y.
Salih, Sana M.
Xu, Xia
Veenstra, Timothy D.
Saeed, Muhammad
Theiler, Shaleen K.
Diaz-Arrastia, Concepcion R.
Salama, Salama A.
TI The effect of tamoxifen and raloxifene on estrogen metabolism and
endometrial cancer risk
SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
LA English
DT Article
DE Endometrial cancer; Estrogen metabolism; Tamoxifen; Raloxifene
ID PROTEIN-COUPLED RECEPTOR; PREGNANE-X-RECEPTOR; BREAST-CANCER;
DNA-ADDUCTS; 17-BETA-HYDROXYSTEROID DEHYDROGENASE; AROMATASE INHIBITORS;
ANTIESTROGEN EM-800; MASS-SPECTROMETRY; GLANDULAR CELLS; UP-REGULATION
AB Selective estrogen receptor modulators (SERMs) demonstrate differential endometrial cancer (EC) risk. While tamoxifen (TAM) use increases the risk of endometrial hyperplasia and malignancy, raloxifene (RAL) has neutral effects on the uterus. How TAM increases the risk of EC and why TAM and RAL differentially modulate the risk for EC, however, remain elusive. Here, we tested the hypothesis that TAM increases the risk for EC, at least in part, by enhancing the local estrogen biosynthesis and directing estrogen metabolism towards the formation of genotoxic and hormonally active estrogen metabolites. In addition, the differential effects of TAM and RAL in EC risk are attributed to their differential effect on estrogen metabolism/metabolites. The endometrial cancer cell line (Ishikawa cells) and the nonmalignant immortalized human endometrial glandular cell line (EM1) were used for the study. The profile of estrogen/estrogen metabolites (EM), depurinating estrogen-DNA adducts, and the expression of estrogen-metabolizing enzymes in cells treated with 17 beta-estradiol (E2) alone or in combination with TAM or RAL were investigated using high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS(2)), ultraperformance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS), and Western blot analysis, respectively. TAM significantly increased the total EM and enhanced the formation of hormonally active and carcinogenic estrogen metabolites, 4-hydroxestrone (4-OHE1) and 16 alpha-hydroxyestrone, with concomitant reduction in the formation of antiestrogenic and anticarcinogenic 2-hydroxyestradiol and 2-methoxyestradiol. Furthermore, TAM increased the formation of depurinating estrogen-DNA adducts 4-OHE1 [2]-1-N7Guanine and 4-OHE1 [2]-1-N3 Adenine. TAM-induced alteration in EM and depurinating DNA adduct formation is associated with altered expression of estrogen metabolizing enzymes CYP1A1, CYP1B1, COMT, NQO1, and SF-1 as revealed by Western blot analysis. In contrast to TAM, RAL has minimal effect on EM, estrogen-DNA adduct formation, or estrogen-metabolizing enzymes expression. These data show that TAM perturbs the balance of estrogen-metabolizing enzymes and alters the disposition of estrogen metabolites, which can explain, at least in part, the mechanism for TAM-induced EC. These results also implicate the differential effect of TAM and RAL on estrogen metabolism/metabolites as a potential mechanism for their disparate effects on the endometrium. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Theiler, Shaleen K.; Diaz-Arrastia, Concepcion R.; Salama, Salama A.] Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA.
[Williams-Brown, Marian Y.; Theiler, Shaleen K.; Diaz-Arrastia, Concepcion R.; Salama, Salama A.] Univ Texas Med Branch, Dept Obstet & Gynecol, Galveston, TX 77555 USA.
[Salih, Sana M.] Univ Wisconsin, Dept Obstet & Gynecol, Madison, WI 53792 USA.
[Xu, Xia; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Saeed, Muhammad] Univ Nebraska Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA.
RP Salama, SA (reprint author), Baylor Coll Med, Dept Obstet & Gynecol, 1 Baylor Plaza MS BCM 610, Houston, TX 77030 USA.
EM mywillia@utmb.edu; salih@wisc.edu; XuX@mail.nih.gov;
veenstrat@mail.nih.gov; msaeed@unmc.edu; shaleen.theiler@yahoo.com;
arrastia@bcm.tmc.edu; salama@bcm.edu
OI theiler, shaleen/0000-0002-6881-6319; Williams-Brown,
Marian/0000-0001-5034-5152
FU NICHD NIH HHS [K12 HD055894]
NR 55
TC 22
Z9 24
U1 0
U2 7
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-0760
J9 J STEROID BIOCHEM
JI J. Steroid Biochem. Mol. Biol.
PD SEP
PY 2011
VL 126
IS 3-5
BP 78
EP 86
DI 10.1016/j.jsbmb.2011.05.001
PG 9
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 797FQ
UT WOS:000293110300004
PM 21600284
ER
PT J
AU Sullivan, JM
Landoure, G
Martinez, TL
Burnett, B
Kong, L
Sahin, B
Gaudet, R
Lloyd, TE
Sumner, CJ
AF Sullivan, J. M.
Landoure, G.
Martinez, T. L.
Burnett, B.
Kong, L.
Sahin, B.
Gaudet, R.
Lloyd, T. E.
Sumner, C. J.
TI DOMINANT TRPV4 MUTATIONS IN HEREDITARY NEUROPATHIES
SO JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
LA English
DT Meeting Abstract
CT Meeting of the Peripheral-Nerve-Society
CY JUN 25-29, 2011
CL Potomac, MD
SP Peripheral Nerve Soc
C1 [Sullivan, J. M.; Martinez, T. L.; Kong, L.; Sahin, B.; Lloyd, T. E.; Sumner, C. J.] Johns Hopkins Univ, Baltimore, MD USA.
[Landoure, G.; Burnett, B.] NIH, Bethesda, MD 20892 USA.
[Martinez, T. L.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Gaudet, R.] Harvard Univ, Cambridge, MA 02138 USA.
RI Gaudet, Rachelle/I-4133-2014
OI Gaudet, Rachelle/0000-0002-9177-054X
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1085-9489
J9 J PERIPHER NERV SYST
JI J. Peripher. Nerv. Syst.
PD SEP
PY 2011
VL 16
SU 3
BP S133
EP S133
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 802KS
UT WOS:000293510300288
ER
PT J
AU Louis, GMB
Schisterman, EF
Sweeney, AM
Wilcosky, TC
Gore-Langton, RE
Lynch, CD
Barr, DB
Schrader, SM
Kim, S
Chen, Z
Sundaram, R
AF Louis, Germaine M. Buck
Schisterman, Enrique F.
Sweeney, Anne M.
Wilcosky, Timothy C.
Gore-Langton, Robert E.
Lynch, Courtney D.
Barr, Dana Boyd
Schrader, Steven M.
Kim, Sungduk
Chen, Zhen
Sundaram, Rajeshwari
CA LIFE Study
TI Designing prospective cohort studies for assessing reproductive and
developmental toxicity during sensitive windows of human reproduction
and development - the LIFE Study
SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY
LA English
DT Article
DE cohort; environment; fecundity; fertility; LIFE Study; preconception;
pregnancy; study design; enrolment
ID EARLY-PREGNANCY LOSS; SPONTANEOUS-ABORTION; DYSGENESIS SYNDROME;
RECRUITMENT; FERTILITY; FECUNDITY; OBESITY; STYLE; TIME; RISK
AB The relationship between the environment and human fecundity and fertility remains virtually unstudied from a couple-based perspective in which longitudinal exposure data and biospecimens are captured across sensitive windows. In response, we completed the LIFE Study with methodology that intended to empirically evaluate a priori purported methodological challenges:
implementation of population-based sampling frameworks suitable for recruiting couples planning pregnancy;
obtaining environmental data across sensitive windows of reproduction and development;
home-based biospecimen collection; and
development of a data management system for hierarchical exposome data.
We used two sampling frameworks (i.e. fish/wildlife licence registry and a direct marketing database) for 16 targeted counties with presumed environmental exposures to persistent organochlorine chemicals to recruit 501 couples planning pregnancies for prospective longitudinal follow-up while trying to conceive and throughout pregnancy. Enrolment rates varied from <1% of the targeted population (n = 424 423) to 42% of eligible couples who were successfully screened; 84% of the targeted population could not be reached, while 36% refused screening. Among enrolled couples, similar to 85% completed daily journals while trying; 82% of pregnant women completed daily early pregnancy journals, and 80% completed monthly pregnancy journals. All couples provided baseline blood/urine samples; 94% of men provided one or more semen samples and 98% of women provided one or more saliva samples. Women successfully used urinary fertility monitors for identifying ovulation and home pregnancy test kits.
Couples can be recruited for preconception cohorts and will comply with intensive data collection across sensitive windows. However, appropriately sized sampling frameworks are critical, given the small percentage of couples contacted found eligible and reportedly planning pregnancy at any point in time.
C1 [Louis, Germaine M. Buck; Schisterman, Enrique F.; Kim, Sungduk; Chen, Zhen; Sundaram, Rajeshwari] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD 20852 USA.
[Sweeney, Anne M.] Texas A&M Hlth Sci Ctr, Sch Rural Publ Hlth, College Stn, TX USA.
[Wilcosky, Timothy C.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Gore-Langton, Robert E.] EMMES Corp, Rockville, MD USA.
[Lynch, Courtney D.] Ohio State Univ, Coll Med, Dept Obstet & Gynecol, Columbus, OH 43210 USA.
[Barr, Dana Boyd] Emory Univ, Rollins Sch Publ Hlth, Dept Environm & Occupat Hlth, Atlanta, GA 30322 USA.
[Schrader, Steven M.] NIOSH, Div Appl Res & Technol, Cincinnati, OH 45226 USA.
RP Louis, GMB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd, Rockville, MD 20852 USA.
EM louisg@mail.nih.gov
RI Barr, Dana/E-6369-2011; Barr, Dana/E-2276-2013;
OI Sundaram, Rajeshwari/0000-0002-6918-5002; Schisterman,
Enrique/0000-0003-3757-641X; Buck Louis, Germaine/0000-0002-1774-4490
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [N01-HD-3-3355, N01-HD-3-3356, N01-HD-3-3358]
FX This study was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (contracts #N01-HD-3-3355, N01-HD-3-3356, N01-HD-3-3358).
The authors acknowledge the support of the Texas Parks and Wildlife
Department in providing the database for study purposes. The authors
have no competing interests.
NR 22
TC 69
Z9 69
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-5022
EI 1365-3016
J9 PAEDIATR PERINAT EP
JI Paediatr. Perinat. Epidemiol.
PD SEP
PY 2011
VL 25
IS 5
BP 413
EP 424
DI 10.1111/j.1365-3016.2011.01205.x
PG 12
WC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
SC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
GA 804MV
UT WOS:000293658800002
ER
PT J
AU Parker, CB
Hogue, CJR
Koch, MA
Willinger, M
Reddy, UM
Thorsten, VR
Dudley, DJ
Silver, RM
Coustan, D
Saade, GR
Conway, D
Varner, MW
Stoll, B
Pinar, H
Bukowski, R
Carpenter, M
Goldenberg, R
AF Parker, Corette B.
Hogue, Carol J. R.
Koch, Matthew A.
Willinger, Marian
Reddy, Uma M.
Thorsten, Vanessa R.
Dudley, Donald J.
Silver, Robert M.
Coustan, Donald
Saade, George R.
Conway, Deborah
Varner, Michael W.
Stoll, Barbara
Pinar, Halit
Bukowski, Radek
Carpenter, Marshall
Goldenberg, Robert
CA Stillbirth Collaborative Res Netwo
TI Stillbirth Collaborative Research Network: design, methods and
recruitment experience
SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY
LA English
DT Article
DE SCRN; stillbirth; study methodology
ID MATERNAL ANXIETY; LATE PREGNANCY; RISK-FACTORS; BIRTH; VARIABLES;
STRESS; RATES
AB The Stillbirth Collaborative Research Network (SCRN) has conducted a multisite, population-based, case-control study, with prospective enrolment of stillbirths and livebirths at the time of delivery. This paper describes the general design, methods and recruitment experience. The SCRN attempted to enrol all stillbirths and a representative sample of livebirths occurring to residents of pre-defined geographical catchment areas delivering at 59 hospitals associated with five clinical sites. Livebirths <32 weeks gestation and women of African descent were oversampled. The recruitment hospitals were chosen to ensure access to at least 90% of all stillbirths and livebirths to residents of the catchment areas. Participants underwent a standardised protocol including maternal interview, medical record abstraction, placental pathology, biospecimen testing and, in stillbirths, post-mortem examination. Recruitment began in March 2006 and was completed in September 2008 with 663 women with a stillbirth and 1932 women with a livebirth enrolled, representing 69% and 63%, respectively, of the women identified. Additional surveillance for stillbirths continued until June 2009 and a follow-up of the case-control study participants was completed in December 2009.
Among consenting women, there were high consent rates for the various study components. For the women with stillbirths, 95% agreed to a maternal interview, chart abstraction and a placental pathological examination; 91% of the women with a livebirth agreed to all of these components. Additionally, 84% of the women with stillbirths agreed to a fetal post-mortem examination. This comprehensive study is poised to systematically study a wide range of potential causes of, and risk factors for, stillbirths and to better understand the scope and incidence of the problem.
C1 [Parker, Corette B.; Koch, Matthew A.; Thorsten, Vanessa R.] RTI Int, Res Triangle Pk, NC 27709 USA.
[Hogue, Carol J. R.] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
[Willinger, Marian; Reddy, Uma M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Bethesda, MD USA.
[Dudley, Donald J.; Conway, Deborah] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Silver, Robert M.; Varner, Michael W.] Univ Utah, Sch Med, Salt Lake City, UT USA.
[Coustan, Donald; Pinar, Halit; Carpenter, Marshall] Brown Univ, Sch Med, Providence, RI 02912 USA.
[Saade, George R.; Bukowski, Radek] Univ Texas Med Branch Galveston, Galveston, TX USA.
[Stoll, Barbara] Emory Univ, Sch Med, Atlanta, GA USA.
[Goldenberg, Robert] Drexel Univ, Sch Med, Philadelphia, PA 19104 USA.
RP Parker, CB (reprint author), RTI Int, 3040 E Cornwallis Rd, Res Triangle Pk, NC 27709 USA.
EM rette@rti.org
RI Bukowski, Radek/B-6976-2013; Hogue, Carol/H-5442-2012; Varner,
Michael/K-9890-2013
OI Varner, Michael/0000-0001-9455-3973
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [U01-HD045954, U10-HD045953, U10-HD045925, U10-HD045952,
U10-HD045955, U10-HD045944]
FX The authors gratefully acknowledge the cooperation of the study
participants, the staff members of the participating hospitals and the
members of the NICHD Scientific Advisory and Safety Monitoring Board:
Reverend Phillip Cato, PhD; James W. Collins, Jr, MD, MPH; Terry Dwyer,
MD, MPH; William P. Fifer, PhD; John Ilekis, PhD; Marc Incerpi, MD;
George Macones, MD, MSCE; Jeff Murray, MD; Richard M. Pauli, MD, PhD;
Raymond W. Redline, MD; Elizabeth Thom, PhD (chair). A list of
participating hospitals is given in Appendix S1. This study was
supported by the Eunice Kennedy Shriver National Institute of Child
Health and Human Development through the Cooperative Agreement mechanism
(U01-HD045954, U10-HD045953, U10-HD045925, U10-HD045952, U10-HD045955,
U10-HD045944).
NR 29
TC 19
Z9 19
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-5022
EI 1365-3016
J9 PAEDIATR PERINAT EP
JI Paediatr. Perinat. Epidemiol.
PD SEP
PY 2011
VL 25
IS 5
BP 425
EP 435
DI 10.1111/j.1365-3016.2011.01218.x
PG 11
WC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
SC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
GA 804MV
UT WOS:000293658800003
PM 21819424
ER
PT J
AU Mumford, SL
Schisterman, EF
Gaskins, AJ
Pollack, AZ
Perkins, NJ
Whitcomb, BW
Ye, AJ
Wactawski-Wende, J
AF Mumford, Sunni L.
Schisterman, Enrique F.
Gaskins, Audrey J.
Pollack, Anna Z.
Perkins, Neil J.
Whitcomb, Brian W.
Ye, Aijun
Wactawski-Wende, Jean
TI Realignment and multiple imputation of longitudinal data: an application
to menstrual cycle data
SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY
LA English
DT Article
DE menstrual cycle; multiple imputation; statistical methodology;
oestradiol 2; luteinising hormone; diet; fibre; missing data
ID SERUM ESTROGEN CONCENTRATIONS; HIGH-FIBER DIET; PREMENOPAUSAL WOMEN;
FERTILITY MONITOR; HORMONE-LEVELS; BREAST-CANCER; FAT; VARIABILITY;
OVULATION; BIOCYCLE
AB Reproductive hormone levels are highly variable among premenopausal women during the menstrual cycle. Accurate timing of hormone measurement is essential, especially when investigating day-or phase-specific effects. The BioCycle Study used daily urine home fertility monitors to help detect the luteinising hormone (LH) surge in order to schedule visits with biologically relevant windows of hormonal variability. However, as the LH surge is brief and cycles vary in length, relevant hormonal changes may not align with scheduled visits even when fertility monitors are used. Using monitor data, measurements were reclassified according to biological phase of the menstrual cycle to more accurate cycle phase categories. Longitudinal multiple imputation methods were applied after reclassification if no visit occurred during a given menstrual cycle phase. Reclassified cycles had more clearly defined hormonal profiles, with higher mean peak hormones (up to 141%) and reduced variability (up to 71%). We demonstrate the importance of realigning visits to biologically relevant windows when assessing phase-or day-specific effects and the feasibility of applying longitudinal multiple imputation methods. Our method has applications in settings where missing data may occur over time, where daily blood sampling for hormonal measurements is not feasible, and in other areas where timing is essential.
C1 [Mumford, Sunni L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD 20852 USA.
[Whitcomb, Brian W.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Div Biostat & Epidemiol, Amherst, MA 01003 USA.
[Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
RP Mumford, SL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd,7B03M, Rockville, MD 20852 USA.
EM mumfords@mail.nih.gov
RI Pollack, Anna/F-2021-2011;
OI Perkins, Neil/0000-0002-6802-4733; Pollack, Anna/0000-0002-4313-3298;
Schisterman, Enrique/0000-0003-3757-641X
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health
FX This study was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health.
NR 28
TC 16
Z9 16
U1 2
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-5022
EI 1365-3016
J9 PAEDIATR PERINAT EP
JI Paediatr. Perinat. Epidemiol.
PD SEP
PY 2011
VL 25
IS 5
BP 448
EP 459
DI 10.1111/j.1365-3016.2011.01204.x
PG 12
WC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
SC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
GA 804MV
UT WOS:000293658800005
PM 21819426
ER
PT J
AU McLain, AC
Sundaram, R
Cooney, MA
Gollenberg, AL
Louis, GMB
AF McLain, Alexander C.
Sundaram, Rajeshwari
Cooney, Maureen A.
Gollenberg, Audra L.
Louis, Germaine M. Buck
TI Clustering of fecundability within women
SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY
LA English
DT Article
DE conception delay; fecundity; fertility; time to pregnancy; CPP
ID LOW-BIRTH-WEIGHT; PREGNANCY OUTCOMES; TIME; RISK; CONCEPTION;
RECURRENCE; FECUNDITY; VALIDITY; DEFECTS; IMPACT
AB Adverse pregnancy outcomes have long been observed to cluster within women resulting in the inclusion of past reproductive history in clinical assessments and perinatal scoring systems. However, limited study has focused on the clustering of fecundability as measured by time to pregnancy (TTP), despite growing evidence suggestive of a possible association with adverse pregnancy outcomes known to cluster within women. We sought to empirically evaluate the clustering of conception delay, and TTP more globally, in one of the few existing prospective pregnancy cohort studies that captured women's successive pregnancies. The study cohort comprised 544 women who contributed 1119 pregnancies in the US Collaborative Perinatal Project. We used a discrete Cox frailty model to estimate the degree and significance of within-woman clustering of TTP. Women with an initial conception delay (TTP > 6 months) were older, less educated and had higher body mass indices than women not experiencing delays (TTP <= 6 months). Our analysis indicates that there is significant within-woman clustering of TTP (variance of the frailty = 0.80, [95% confidence interval 0.49, 1.11]) after adjusting for baseline maternal age, body mass index and education level. Similar to many other reproductive and perinatal outcomes, our findings suggest that TTP clusters within women. Identifying exposures or behaviours that affect TTP may offer strategies for reducing conception delay in future pregnancy attempts.
C1 [McLain, Alexander C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA.
[Gollenberg, Audra L.] Shenandoah Univ, Dept Publ Hlth, Winchester, VA USA.
RP McLain, AC (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,Rm 7B05K, Rockville, MD 20852 USA.
EM mclaina@mail.nih.gov
OI McLain, Alexander/0000-0002-5475-0670; Sundaram,
Rajeshwari/0000-0002-6918-5002; Buck Louis, Germaine/0000-0002-1774-4490
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX This work was supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development.
NR 37
TC 5
Z9 5
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0269-5022
J9 PAEDIATR PERINAT EP
JI Paediatr. Perinat. Epidemiol.
PD SEP
PY 2011
VL 25
IS 5
BP 460
EP 465
DI 10.1111/j.1365-3016.2011.01219.x
PG 6
WC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
SC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
GA 804MV
UT WOS:000293658800006
PM 21819427
ER
PT J
AU Zhu, JL
Obel, C
Basso, O
Henriksen, TB
Bech, BH
Hvidtjorn, D
Olsen, J
AF Zhu, Jin Liang
Obel, Carsten
Basso, Olga
Henriksen, Tine B.
Bech, Bodil H.
Hvidtjorn, Dorte
Olsen, Jorn
TI Infertility, infertility treatment and behavioural problems in the
offspring
SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY
LA English
DT Article
DE childhood behaviour; child development; infertility; infertility
treatment; Strengths and Difficulties Questionnaire (SDQ)
ID DIFFICULTIES QUESTIONNAIRE SDQ; IN-VITRO FERTILIZATION; ASSISTED
REPRODUCTION FAMILIES; PARENT-CHILD RELATIONSHIPS; AUTISM SPECTRUM
DISORDERS; NATIONAL BIRTH COHORT; PSYCHOMETRIC PROPERTIES;
PSYCHIATRIC-DISORDERS; COMMUNITY SAMPLE; SWEDISH VERSION
AB Behavioural patterns in children of infertile couples may be influenced by both the underlying causes of infertility and stress in the couples. Treatment procedures, such as culture media and manipulation of gametes and embryos, may also result in developmental problems. We examined behavioural problems in children as a function of infertility and infertility treatment, using data from three population-based birth cohorts in Denmark (Aalborg-Odense Birth Cohort, Aarhus Birth Cohort and Danish National Birth Cohort). Information on time to pregnancy and infertility treatment was collected during pregnancy. Children aged between 7 and 21 years were assessed using the Strengths and Difficulties Questionnaire (SDQ). The SDQ was completed by mothers in all cohorts and, in addition, by teachers in the Aarhus cohort and by children themselves in the Aalborg-Odense cohort. Children born after a time to pregnancy of > 12 months and no infertility treatment had a behavioural pattern similar to children of fertile parents. Teachers reported a higher total difficulties score for children born after infertility treatment, but no significant differences were seen on any subscales of the teachers' report, and neither the mothers nor the children reported any differences on the total difficulties score and the prosocial behaviour score. Our results are thus overall reassuring regarding behavioural problems in children born to infertile couples, regardless of infertility treatment.
C1 [Zhu, Jin Liang] Univ Aarhus, Danish Epidemiol Sci Ctr, Sch Publ Hlth, Dept Epidemiol, DK-8000 Aarhus C, Denmark.
[Obel, Carsten; Henriksen, Tine B.] Aarhus Univ Hosp, Dept Paediat, DK-8000 Aarhus, Denmark.
[Basso, Olga] NIEHS, Epidemiol Branch, NIH, Durham, NC USA.
[Olsen, Jorn] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA.
[Basso, Olga] McGill Univ, Dept Obstet & Gynecol, Montreal, PQ H3A 2T5, Canada.
RP Zhu, JL (reprint author), Univ Aarhus, Danish Epidemiol Sci Ctr, Sch Publ Hlth, Dept Epidemiol, Bartholins Alle 2, DK-8000 Aarhus C, Denmark.
EM zjl@soci.au.dk
RI Basso, Olga/E-5384-2010; Olsen, Jorn/F-8801-2015; Bech, Bodil
Hammer/B-9646-2016
OI Basso, Olga/0000-0001-9298-4921; Olsen, Jorn/0000-0001-7462-5140;
FU Danish Medical Research Council [271-05-0115, 271-07-0402, 09-063477];
NIH, National Institute of Environmental Health Sciences [Z01 ES044003];
Danish National Research Foundation
FX The authors thank Matthew P. Longnecker and two anonymous reviewers for
providing valuable comments on an earlier version of this paper. This
work was supported by grants from the Danish Medical Research Council
(271-05-0115, 271-07-0402 and 09-063477) and, in part, by the Intramural
Program of the NIH, National Institute of Environmental Health Sciences
(Z01 ES044003). The Danish National Research Foundation has established
the Danish Epidemiology Science Centre, which initiated and created the
Danish National Birth Cohort. The cohort is furthermore a result of a
major grant from this Foundation. Additional support for the Danish
National Birth Cohort is obtained from the Pharmacy Foundation, the
Egmont Foundation, the March of Dimes Birth Defects Foundation, the
Augustinus Foundation and the Health Foundation.
NR 54
TC 8
Z9 9
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-5022
EI 1365-3016
J9 PAEDIATR PERINAT EP
JI Paediatr. Perinat. Epidemiol.
PD SEP
PY 2011
VL 25
IS 5
BP 466
EP 477
DI 10.1111/j.1365-3016.2011.01220.x
PG 12
WC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
SC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
GA 804MV
UT WOS:000293658800007
PM 21819428
ER
PT J
AU Vasudevan, K
Sztein, JM
AF Vasudevan, Kuzhalini
Sztein, Jorge M.
TI Treatment of sperm with extracellular adenosine 5 '-triphosphate
improves the in vitro fertility rate of inbred and genetically modified
mice with low fertility
SO THERIOGENOLOGY
LA English
DT Article
DE Genetically modified mice; In vitro fertilization; Extracellular ATP;
Fertility
ID MALE FACTOR INFERTILITY; MOUSE SPERM; ACROSOME REACTION; BOVINE
SPERMATOZOA; ACTIVATING-FACTOR; FERTILIZATION; MOTILITY; INVITRO;
CAPACITATION; STRAINS
AB In vitro fertilization (IVF) is one of the most important techniques used for assisted reproduction in mouse colony management. As with natural mating, where mice have varying fertility indices, fertility rates of genetically modified (GM) [transgenic (Tg), knock out (KO) and congenic (Cg)] mice are influenced by their genetic background. Lines of GM mice that have poor fertility have a concomitant poor IVF outcome. Treatment of mouse sperm with extracellular adenosine 5'-triphosphate (ATPe) enhanced in vitro fertilization rates in outbred and hybrid mice. The objective of this study was to analyze the effects of using extracellular adenosine 5'-triphosphate-treated sperm for IVF of inbred wild type, and genetically modified mouse lines, for which standard IVF did not work well. The IVF was performed using the GM mice on C57BL/10SnJ, C57BL/6J, BALB/cJ and NFS/N background strains and wild type (WT) mice such as C57BL/6N, BALB/cAnN, and B6129SF1 strains. Oocytes from superovulated females were fertilized in vitro with sperm from the same background strain, and either treated or not treated with ATPe. The ATPe treatment enhanced IVF outcome in most of the GM and some WT strains, as indicated by the percentage of embryos that progressed to the two-cell stage. There was no marked difference between ATPe treated and control groups for the development rate of two-cell embryos to blastocysts in culture, or in the number of pups born after transfer of two-cell embryos into recipient females. The observed improvement of the IVF results following ATPe treatment of transgenic and KO mouse sperm were a potential solution for improving the outcome of assisted reproduction techniques used for rederivation or for gamete banking. Published by Elsevier Inc.
C1 [Vasudevan, Kuzhalini; Sztein, Jorge M.] NIAID, Assisted Reprod Technol & Cryopreservat Unit, CMB, NIH, Rockville, MD USA.
RP Sztein, JM (reprint author), NIAID, Assisted Reprod Technol & Cryopreservat Unit, CMB, NIH, Rockville, MD USA.
EM szteinj@niaid.nih.gov
OI Sztein, Jorge Mario/0000-0001-7047-2634
FU Comparative Medicine Branch; National Institutes of Allergy and
Infectious Diseases/National Institutes of Health
FX The authors thank Chris McGregor for technical assistance and Dr. Kathy
Perdue for critical reading of the manuscript. We also thank all
scientists who allowed us to use their mice for this study. This
research was supported by Comparative Medicine Branch and the Intramural
Research Program of National Institutes of Allergy and Infectious
Diseases/National Institutes of Health.
NR 31
TC 5
Z9 7
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0093-691X
J9 THERIOGENOLOGY
JI Theriogenology
PD SEP 1
PY 2011
VL 76
IS 4
BP 729
EP 736
DI 10.1016/j.theriogenology.2011.04.005
PG 8
WC Reproductive Biology; Veterinary Sciences
SC Reproductive Biology; Veterinary Sciences
GA 807CC
UT WOS:000293870100017
PM 21601915
ER
PT J
AU Kuranov, AB
Mukhamedyarov, DA
Momynaliev, KT
AF Kuranov, A. B.
Mukhamedyarov, D. A.
Momynaliev, K. T.
TI Characterization of new HLA-A and -B alleles from Kazakhstan
SO TISSUE ANTIGENS
LA English
DT Editorial Material
DE DNA sequencing; human leukocyte antigen; new allele
C1 [Momynaliev, K. T.] Res Inst Physicochem Med, Moscow 119992, Russia.
[Kuranov, A. B.; Mukhamedyarov, D. A.; Momynaliev, K. T.] Natl Biotechnol Ctr, Astana, Kazakhstan.
RP Momynaliev, KT (reprint author), Res Inst Physicochem Med, Malaya Pirogovskaya 1A, Moscow 119992, Russia.
EM dhoroshun@gmail.com
NR 6
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0001-2815
J9 TISSUE ANTIGENS
JI Tissue Antigens
PD SEP
PY 2011
VL 78
IS 3
BP 217
EP 218
DI 10.1111/j.1399-0039.2011.01681.x
PG 2
WC Cell Biology; Immunology; Pathology
SC Cell Biology; Immunology; Pathology
GA 801BP
UT WOS:000293411700009
PM 21732918
ER
PT J
AU Sherrill, J
Mariappan, M
Dominik, P
Hegde, RS
Keenan, RJ
AF Sherrill, John
Mariappan, Malaiyalam
Dominik, Pawel
Hegde, Ramanujan S.
Keenan, Robert J.
TI A Conserved Archaeal Pathway for Tail-Anchored Membrane Protein
Insertion
SO TRAFFIC
LA English
DT Article
DE archaea; ArsA; Get3; insertion; posttranslational; targeting;
tail-anchored membrane proteins; TRC40
ID ENDOPLASMIC-RETICULUM; ER MEMBRANE; GET3; BINDING; COMPLEX
AB Eukaryotic tail-anchored ( TA) membrane proteins are inserted into the endoplasmic reticulum by a posttranslational TRC40 pathway, but no comparable pathway is known in other domains of life. The crystal structure of an archaebacterial TRC40 sequence homolog bound to ADP.AlF(4)(-) reveals characteristic features of eukaryotic TRC40, including a zinc-mediated dimer and a large hydrophobic groove. Moreover, archaeal TRC40 interacts with the transmembrane domain of TA substrates and directs their membrane insertion. Thus, the TRC40 pathway is more broadly conserved than previously recognized.
C1 [Sherrill, John; Dominik, Pawel; Keenan, Robert J.] Univ Chicago, Dept Biochem & Mol Biol, Gordon Ctr Integrat Sci, Chicago, IL 60637 USA.
[Mariappan, Malaiyalam; Hegde, Ramanujan S.] NICHHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
RP Keenan, RJ (reprint author), Univ Chicago, Dept Biochem & Mol Biol, Gordon Ctr Integrat Sci, Room W238, Chicago, IL 60637 USA.
EM bkeenan@uchicago.edu
RI mariappan, malaiyalam/K-9024-2012;
OI Hegde, Ramanujan/0000-0001-8338-852X
FU US DOE [DE-AC02-06CH11357]; NIH [T32 GM008720]; Edward Mallinckrodt, Jr
Foundation
FX Data were collected at beamline 21-IDF at the Advanced Photon Source
(APS), Argonne National Laboratory, and we thank the beamline staff for
support. Use of the Advanced Photon Source, an Office of Science User
Facility operated for the US Department of Energy (DOE) Office of
Science by Argonne National Laboratory, was supported by the US DOE
under Contract No. DE-AC02-06CH11357. We thank Maureen Downing for
cloning the M. thermautotrophicus TRC40 homolog, and Agnieszka Mateja
andMalgorzata Dobosz for help with data collection. This work was
supported by the Intramural Research Program of the NIH (to RSH), NIH
grant T32 GM008720 (to JS), an Edward Mallinckrodt, Jr Foundation Grant
(to RJK) and NIH Grant R01 GM086487 (to RJK). JS and PD carried out
cloning, protein purification and crystallization. JS, PD and RJK
performed data collection and JS carried out the structure determination
and model building. MM and RSH performed the substrate-binding and
membrane insertion assays. RJK conceived the project, guided experiments
and wrote the article. All authors discussed the results and commented
on the manuscript. The X-ray structure of
Mg2+ADP.AlF4- bound M.
thermautotrophicus TRC40 is deposited in the Protein Data Bank under ID
code 3zq6.
NR 23
TC 6
Z9 6
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1398-9219
J9 TRAFFIC
JI Traffic
PD SEP
PY 2011
VL 12
IS 9
BP 1119
EP 1123
DI 10.1111/j.1600-0854.2011.01229.x
PG 5
WC Cell Biology
SC Cell Biology
GA 806HP
UT WOS:000293797200003
PM 21658170
ER
PT J
AU Mathews, JA
Ford, J
Norton, S
Kang, D
Dellinger, A
Gibb, DR
Ford, AQ
Massay, H
Kepley, CL
Scherle, P
Keegan, AD
Conrad, DH
AF Mathews, J. A.
Ford, J.
Norton, S.
Kang, D.
Dellinger, A.
Gibb, D. R.
Ford, A. Q.
Massay, H.
Kepley, C. L.
Scherle, P.
Keegan, A. D.
Conrad, D. H.
TI A potential new target for asthma therapy: A Disintegrin and
Metalloprotease 10 (ADAM10) involvement in murine experimental asthma
SO ALLERGY
LA English
DT Article
DE ADAM10; asthma; CD23; IgE; Th2
ID INDUCED AIRWAY HYPERREACTIVITY; IGE PRODUCTION; ALLERGIC DISEASE;
IN-VIVO; CD23; INFLAMMATION; CELLS; INHIBITION; MODEL; LUNG
AB Background: Elevated levels of CD23, a natural regulator of IgE production, have been shown to decrease the signs of lung inflammation in mice. The aim of this study was to study the involvement of ADAM10, the primary CD23 sheddase, in experimental asthma.
Methods: ADAM10 was blocked either by using mice with a B-cell-specific deletion of the protease or pharmacologically by intranasal administration of selective ADAM10 inhibitors. Airway hypersensitivity (AHR) and bronchoaveolar lavage fluid (BALF) eosinophilia and select BALF cytokine/chemokine levels were then determined.
Results: Using an IgE and mast cell-dependent mouse model, B-cell-specific ADAM10(-/-) mice (C57B/6 background) exhibited decreased eosinophilia and AHR when compared with littermate (LM) controls. Treatment of C57B/6 mice with selective inhibitors of ADAM10 resulted in an even further decrease in BALF eosinophilia, as compared with the ADAM10(-/-) animals. Even in the Th2 selective strain, Balb/c, BALF eosinophilia was reduced from 60% to 23% respectively. In contrast, when an IgE/mast cell-independent model of lung inflammation was used, the B-cell ADAM10(-/-) animals and ADAM10 inhibitor treated animals had lung inflammation levels that were similar to the controls.
Conclusions: These results thus show that ADAM10 is important in the progression of IgE-dependent lung inflammation. The use of the inhibitor further suggested that ADAM10 was important for maintaining Th2 levels in the lung. These results thus suggest that decreasing ADAM10 activity could be beneficial in controlling asthma and possibly other IgE-dependent diseases.
C1 [Mathews, J. A.; Norton, S.; Kang, D.; Gibb, D. R.; Conrad, D. H.] Virginia Commonwealth Univ, Sch Med, Dept Microbiol & Immunol, Richmond, VA 23298 USA.
[Ford, J.] NCI, Canc & Inflammatory Program, Frederick, MD 21701 USA.
[Dellinger, A.; Kepley, C. L.] NanoImmunol Luna Innovat, Danville, VA USA.
[Ford, A. Q.] Board Populat Hlth Inst Med, Washington, DC USA.
[Massay, H.] Virginia Commonwealth Univ, Sch Med, Dept Pathol, Richmond, VA 23298 USA.
[Scherle, P.] Incyte Corp, Wilmington, DE USA.
[Keegan, A. D.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
RP Conrad, DH (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Microbiol & Immunol, POB 980678, Richmond, VA 23298 USA.
EM dconrad@vcu.edu
RI Gung, Amber/D-9842-2011
FU NIH-NINDS Center [5P30NSD4763-02]; NIH [RO1AI18697, 1U19AI077435]
FX We thank John Tew and Keith Brooks for their review and comments on the
manuscript. Also we thank Drew Jones for his help in developing the
IgE/mast cell-independent model and Jorge Almenara for his help in
sectioning of the lungs. Microscopy was performed at the VCU Department
of Anatomy and Neurobiology Microscopy Facility, supported, in part,
with funding from NIH-NINDS Center core grand (5P30NSD4763-02). Support
for this work came from the NIH grants RO1AI18697 and 1U19AI077435.
NR 32
TC 21
Z9 21
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0105-4538
J9 ALLERGY
JI Allergy
PD SEP
PY 2011
VL 66
IS 9
BP 1193
EP 1200
DI 10.1111/j.1398-9995.2011.02614.x
PG 8
WC Allergy; Immunology
SC Allergy; Immunology
GA 800EQ
UT WOS:000293343000008
PM 21557750
ER
PT J
AU Nair, V
Dai, ZL
Khan, M
Ciolino, HP
AF Nair, Vidhya
Dai, Zhaoli
Khan, Maruf
Ciolino, Henry P.
TI Pomegranate Extract Induces Cell Cycle Arrest and Alters Cellular
Phenotype of Human Pancreatic Cancer Cells
SO ANTICANCER RESEARCH
LA English
DT Article
DE Pomegranate; pancreatic cancer cells; phytochemicals; cell cycle arrest
ID PUNICA-GRANATUM L.; IN-VITRO; STEM-CELLS; ANTIOXIDANT; CHEMOPREVENTION;
CHEMOTHERAPY; POLYPHENOLS; PACLITAXEL; GROWTH; LINES
AB Background: Pomegranate extract (PE) is a standardized whole-fruit extract of pomegranate, a fruit with known anticancer properties. Materials and Methods: PANC-1 and AsPC-1 human pancreatic cancer cells were used as in vitro models to test the effects of PE. Results: PE treatment induced cell cycle arrest and inhibited cell proliferation in PANC-1 cells. PE treatment increased the proportion of cells lacking CD44 and CD24 expression, which are associated with increased tumor-initiating ability, demonstrating that PE altered cell phenotype. PE was more effective in inhibiting the proliferation of PANC-1 cells than the clinically used dose of paclitaxel. Similar results were obtained in the AsPC-1 cell line. Individual pomegranate phytochemicals were only modestly effective in inhibiting cell proliferation, suggesting that unidentified phytochemicals are responsible for the inhibitory effect of PE. Conclusion: These data suggest that PE is a promising candidate for further preclinical testing for treatment of human pancreatic cancer.
C1 [Ciolino, Henry P.] NCI, Off Canc Ctr, Rockville, MD 20892 USA.
[Nair, Vidhya; Dai, Zhaoli; Khan, Maruf] Univ Texas Austin, Dept Nutr Sci, Austin, TX 78712 USA.
RP Ciolino, HP (reprint author), NCI, Off Canc Ctr, Bldg 6116,Room 7002, Rockville, MD 20892 USA.
EM ciolinoh@mail.nih.gov
NR 25
TC 5
Z9 5
U1 1
U2 5
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 2011
VL 31
IS 9
BP 2699
EP 2704
PG 6
WC Oncology
SC Oncology
GA 800KG
UT WOS:000293357700003
PM 21868510
ER
PT J
AU Cai, T
Hirai, H
Zhang, G
Zhang, M
Takahashi, N
Kasai, H
Satin, LS
Leapman, RD
Notkins, AL
AF Cai, T.
Hirai, H.
Zhang, G.
Zhang, M.
Takahashi, N.
Kasai, H.
Satin, L. S.
Leapman, R. D.
Notkins, A. L.
TI Deletion of Ia-2 and/or Ia-2 beta in mice decreases insulin secretion by
reducing the number of dense core vesicles
SO DIABETOLOGIA
LA English
DT Article
DE Autophagy; Capacitance; Dense core vesicle; Diabetes; Electron
microscopy; Gene knockout; Insulin; Pancreatic islet; Protein tyrosine
phosphates; Two-photon microscopy
ID PROTEIN-TYROSINE-PHOSPHATASE; PANCREATIC BETA-CELLS; DEPENDENT
DIABETES-MELLITUS; TARGETED DISRUPTION; DOUBLE KNOCKOUT; CA2+ CHANNELS;
ISLET CELLS; GLUCOSE; GRANULES; EXOCYTOSIS
AB Islet antigen 2 (IA-2) and IA-2 beta are dense core vesicle (DCV) transmembrane proteins and major autoantigens in type 1 diabetes. The present experiments were initiated to test the hypothesis that the knockout of the genes encoding these proteins impairs the secretion of insulin by reducing the number of DCV.
Insulin secretion, content and DCV number were evaluated in islets from single knockout (Ia-2 [also known as Ptprn] KO, Ia-2 beta [also known as Ptprn2] KO) and double knockout (DKO) mice by a variety of techniques including electron and two-photon microscopy, membrane capacitance, Ca(2+) currents, DCV half-life, lysosome number and size and autophagy.
Islets from single and DKO mice all showed a significant decrease in insulin content, insulin secretion and the number and half-life of DCV (p < 0.05 to 0.001). Exocytosis as evaluated by two-photon microscopy, membrane capacitance and Ca(2+) currents supports these findings. Electron microscopy of islets from KO mice revealed a marked increase (p < 0.05 to 0.001) in the number and size of lysosomes and enzymatic studies showed an increase in cathepsin D activity (p < 0.01). LC3 protein, an indicator of autophagy, also was increased in islets of KO compared with wild-type mice (p < 0.05 to 0.01) suggesting that autophagy might be involved in the deletion of DCV.
We conclude that the decrease in insulin content and secretion, resulting from the deletion of Ia-2 and/or Ia-2 beta, is due to a decrease in the number of DCV.
C1 [Cai, T.; Hirai, H.; Notkins, A. L.] NIDCR, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA.
[Zhang, G.; Leapman, R. D.] Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Bethesda, MD USA.
[Zhang, M.; Satin, L. S.] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA USA.
[Takahashi, N.; Kasai, H.] Univ Tokyo, Ctr Dis Biol & Integrat Med, Lab Struct Physiol, Tokyo, Japan.
[Satin, L. S.] Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA.
[Satin, L. S.] Univ Michigan, Sch Med, Brehm Diabet Ctr, Ann Arbor, MI 48109 USA.
RP Cai, T (reprint author), NIDCR, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA.
EM tcai@mail.nih.gov; anotkins@dir.nidcr.nih.gov
FU NIH (NIDCR and NIBIB); NIH [RO1 DK46409]
FX We thank C. Wohlenberg (NIDCR/NIH, Bethesda, MD, USA) for technical
help. This research was supported in part by the Intramural Research
Program of the NIH (NIDCR and NIBIB) and grant NIH RO1 DK46409 for the
Satin laboratory. The authors thank A. Sherman (NIDDK/NIH, Bethesda, MD,
USA) and M. Merrins (L. S. Satin's lab) for helpful discussions.
NR 43
TC 28
Z9 31
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
J9 DIABETOLOGIA
JI Diabetologia
PD SEP
PY 2011
VL 54
IS 9
BP 2347
EP 2357
DI 10.1007/s00125-011-2221-6
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 802XS
UT WOS:000293544900020
PM 21732083
ER
PT J
AU Chaves, LF
Keogh, CL
Nguyen, AM
Decker, GM
Vazquez-Prokopec, GM
Kitron, UD
AF Chaves, L. F.
Keogh, C. L.
Nguyen, A. M.
Decker, G. M.
Vazquez-Prokopec, G. M.
Kitron, U. D.
TI Combined sewage overflow accelerates immature development and increases
body size in the urban mosquito Culex quinquefasciatus
SO JOURNAL OF APPLIED ENTOMOLOGY
LA English
DT Article
DE density dependence; phenotypic plasticity; sewage
ID AEDES-AEGYPTI DIPTERA; WEST-NILE-VIRUS; TREE-HOLE ECOSYSTEMS; CULICIDAE;
LARVAL; INFECTION; TRANSMISSION; TRITAENIORHYNCHUS; SUSCEPTIBILITY;
OVIPOSITION
AB In urban landscapes the crowding of humans and their waste products may alleviate intra-specific interactions of common mosquitoes. Here, we present the results of a semi-natural experiment addressing the effects of water from a sewage overflow stream on density dependent fitness components and phenotypic traits of a common tropical and subtropical urban mosquito, Culex quinquefasciatus Say (Diptera: Culicidae). This semi-natural experiment was designed to quantify the relative importance of density dependence, weather forces and water quality on larval mortality, sex ratio and size at adult emergence. Results showed that mortality hazards were independent of larval density, decreased in sewage overflow water and increased with minimum temperatures. Under all rearing conditions adult mosquito size decreased with density. Mosquitoes from sewage overflow water emerged faster, were bigger and had an increased ratio of females to males. All these traits may contribute to the regulation of mosquito populations.
C1 [Chaves, L. F.; Decker, G. M.; Vazquez-Prokopec, G. M.; Kitron, U. D.] Emory Univ, Dept Environm Studies, Atlanta, GA 30322 USA.
[Keogh, C. L.] Univ Georgia, Odum Sch Ecol, Athens, GA 30602 USA.
[Nguyen, A. M.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA.
[Kitron, U. D.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Chaves, LF (reprint author), Emory Univ, Dept Environm Studies, 400 Dowman Dr,Suite E510, Atlanta, GA 30322 USA.
EM lfchave@emory.edu
RI Chaves, Luis Fernando/F-3448-2010
OI Chaves, Luis Fernando/0000-0002-5301-2764
FU Emory University; Department of Environmental Studies; NSF
FX This work was funded by Emory University and the Lester fund -
Department of Environmental Studies. Alexandra Van Nostrand and Will
Galvin provided technical support. LFC and UK also thank the Research
and Policy for Infectious Disease Dynamics (RAPIDD) program of the
Science and Technology Directorate and the Fogarty International Center,
National Institutes of Health program on mosquito borne diseases, for
helpful discussions in the context of this manuscript. CLK was supported
by a NSF Pre-Doctoral Fellowship.
NR 42
TC 15
Z9 15
U1 5
U2 26
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0931-2048
J9 J APPL ENTOMOL
JI J. Appl. Entomol.
PD SEP
PY 2011
VL 135
IS 8
BP 611
EP 620
DI 10.1111/j.1439-0418.2010.01580.x
PG 10
WC Entomology
SC Entomology
GA 801MT
UT WOS:000293444200005
ER
PT J
AU Massilamany, C
Gangaplara, A
Gardner, DJ
Musser, JM
Steffen, D
Somerville, GA
Reddy, J
AF Massilamany, Chandirasegaran
Gangaplara, Arunakumar
Gardner, Donald J.
Musser, James M.
Steffen, David
Somerville, Greg A.
Reddy, Jay
TI TCA cycle inactivation in Staphylococcus aureus alters nitric oxide
production in RAW 264.7 cells
SO MOLECULAR AND CELLULAR BIOCHEMISTRY
LA English
DT Article
DE Staphylococcus aureus; Aconitase; Nitric oxide; RAW 264.7 cells; Immune
evasion
ID INNATE IMMUNITY; HOST-DEFENSE; KAPPA-B; SYNTHASE; EXPRESSION;
MACROPHAGES; ACTIVATION; INDUCTION; VIRULENCE; DEHYDROGENASE
AB Inactivation of the Staphylococcus aureus tricarboxylic acid (TCA) cycle delays the resolution of cutaneous ulcers in a mouse soft tissue infection model. In this study, it was observed that cutaneous lesions in mice infected with wild-type or isogenic aconitase mutant S. aureus strains contained comparable inflammatory infiltrates, suggesting the delayed resolution was independent of the recruitment of immune cells. These observations led us to hypothesize that staphylococcal metabolism can modulate the host immune response. Using an in vitro model system involving RAW 264.7 cells, the authors observed that cells cultured with S. aureus aconitase mutant strains produced significantly lower amounts of nitric oxide (NO(aEuro cent)) and an inducible nitric oxide synthase as compared to those cells exposed to wild-type bacteria. Despite the decrease in NO(aEuro cent) synthesis, the expression of antigen-presentation and costimulatory molecules was similar in cells cultured with wild-type and those cultured with aconitase mutant bacteria. The data suggest that staphylococci can evade innate immune responses and potentially enhance their ability to survive in infected hosts by altering their metabolism. This may also explain the occurrence of TCA cycle mutants in clinical S. aureus isolates.
C1 [Massilamany, Chandirasegaran; Gangaplara, Arunakumar; Steffen, David; Somerville, Greg A.; Reddy, Jay] Univ Nebraska, Sch Vet Med & Biomed Sci, Lincoln, NE 68583 USA.
[Gardner, Donald J.] NIAID, Rocky Mt Vet Branch, Lab Human Bacterial Pathogenesis, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
RP Reddy, J (reprint author), Univ Nebraska, Sch Vet Med & Biomed Sci, Room 202,Bldg VBS, Lincoln, NE 68583 USA.
EM nreddy2@unl.edu
RI Somerville, Greg/B-1326-2013; Reddy, Jay/K-7200-2014; Massilamany,
Chandirasegaran/D-9305-2016;
OI Somerville, Greg/0000-0002-0991-8737; Reddy, Jay/0000-0003-4082-9254;
Massilamany, Chandirasegaran/0000-0002-0205-282X; Gangaplara,
Arunakumar/0000-0001-6307-9391
FU Hatch Act; National Center for Research Resources (NIH) [P20-RR-17675];
Redox Biology Center, University of Nebraska-Lincoln; National
Institutes of Health [AI087668]; National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This manuscript is a contribution of the University of Nebraska
Agricultural Research Division, supported in part by funds provided
through the Hatch Act and by the COBRE Program from the National Center
for Research Resources (P20-RR-17675, NIH), Redox Biology Center,
University of Nebraska-Lincoln. Additional funding was provided by the
National Institutes of Health to GAS (AI087668) and by the Intramural
Research Program of the National Institute of Allergy and Infectious
Diseases, National Institutes of Health.
NR 39
TC 6
Z9 6
U1 0
U2 12
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0300-8177
J9 MOL CELL BIOCHEM
JI Mol. Cell. Biochem.
PD SEP
PY 2011
VL 355
IS 1-2
BP 75
EP 82
DI 10.1007/s11010-011-0840-3
PG 8
WC Cell Biology
SC Cell Biology
GA 800ZD
UT WOS:000293405300009
PM 21519920
ER
PT J
AU Leoni, RF
Paiva, FF
Henning, EC
Nascimento, GC
Tannus, A
de Araujo, DB
Silva, AC
AF Leoni, Renata F.
Paiva, Fernando F.
Henning, Erica C.
Nascimento, George C.
Tannus, Alberto
de Araujo, Draulio B.
Silva, Afonso C.
TI Magnetic resonance imaging quantification of regional cerebral blood
flow and cerebrovascular reactivity to carbon dioxide in normotensive
and hypertensive rats
SO NEUROIMAGE
LA English
DT Article
DE Arterial spin labeling; Hypercapnia; Magnetic resonance imaging;
Perfusion; Spontaneously hypertensive rat
ID FUNCTIONAL MRI; ANESTHETIZED RATS; AUTO-REGULATION; ISOFLURANE;
ISCHEMIA; HYPERCAPNIA; RESPONSES; ARTERY; AUTOREGULATION; STIMULATION
AB Hypertension afflicts 25% of the general population and over 50% of the elderly. In the present work, arterial spin labeling MRI was used to non-invasively quantify regional cerebral blood flow (CBE), cerebrovascular resistance and CO(2) reactivity in spontaneously hypertensive rats (SHR) and in normotensive Wistar Kyoto rats (WKY), at two different ages (3 months and 10 months) and under the effects of two anesthetics, alpha-chloralose and 2% isoflurane (1.5 MAC). Repeated CBE measurements were highly consistent, differing by less than 10% and 18% within and across animals, respectively. Under alpha-chloralose, whole brain CBE at normocapnia did not differ between groups (young WKY: 61 3 ml/100 g/min; adult WKY: 62 +/- 4 ml/100 g/min; young SHR: 70 +/- 9 ml/100 g/min: adult SHR: 69 8 ml/100 g/min), indicating normal cerebral autoregulation in SHR. At hypercapnia, CBE values increased significantly, and a linear relationship between CBE and PaCO(2) levels was observed. In contrast, 2% isoflurane impaired cerebral autoregulation. Whole brain CBE in SHR was significantly higher than in WKY rats at normocapnia (young SHR: 139 +/- 25 ml/100 g/min; adult SHR: 104 +/- 23 ml/100 g/min; young WKY: 55 +/- 9 ml/100 g/min; adult WKY: 71 +/- 19 ml/100 g/min). CBE values increased significantly with increasing CO(2): however, there was a clear saturation of CBF at PaCO(2) levels greater than 70 mm Hg in both young and adult rats, regardless of absolute CBE values, suggesting that isoflurane interferes with the vasoclilatory mechanisms of CO(2). This behavior was observed for both cortical and subcortical structures. Under either anesthetic, CO(2) reactivity values in adult SHR were decreased, confirming that hypertension, when combined with age, increases cerebrovascular resistance and reduces cerebrovascular compliance. Published by Elsevier Inc.
C1 [Leoni, Renata F.; Paiva, Fernando F.; Nascimento, George C.; Silva, Afonso C.] Natl Inst Neurol Disorders & Stroke, Cerebral Microcirculat Unit, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
[Leoni, Renata F.; de Araujo, Draulio B.] Univ Sao Paulo, Dept Math & Phys, FFCLRP, BR-14040901 Ribeirao Preto, SP, Brazil.
[Paiva, Fernando F.; Tannus, Alberto] Univ Sao Paulo, CIERMag Ctr Imagens & Espectroscopia Vivo Ressona, Inst Phys Sao Carlos, BR-13560970 Sao Carlos, SP, Brazil.
[Henning, Erica C.] Natl Inst Neurol Disorders & Stroke, Sect Stroke Diagnost & Therapeut, Bethesda, MD 20892 USA.
[de Araujo, Draulio B.] Univ Fed Rio Grande do Norte, Hosp Univ Oliofre Lopes, BR-59012300 Natal, RN, Brazil.
RP Silva, AC (reprint author), Natl Inst Neurol Disorders & Stroke, Cerebral Microcirculat Unit, Lab Funct & Mol Imaging, NIH, 10 Ctr Dr MSC 1065,Bldg 10 Room 81D106, Bethesda, MD 20892 USA.
EM SilvaA@ninds.nih.gov
RI Paiva, Fernando/C-1429-2012; Araujo, Draulio/I-6038-2012; Sao Carlos
Institute of Physics, IFSC/USP/M-2664-2016; Tannus, Alberto/B-9821-2012;
OI Paiva, Fernando/0000-0002-8989-9707; Araujo,
Draulio/0000-0002-6934-2485; Tannus, Alberto/0000-0002-1675-1971; Leoni,
Renata/0000-0002-4568-0746
FU NIH; NINDS; FAPESP [2006/05706-5, 2003/13399-7, 2005/56663-1]
FX This research was supported by the Intramural Research Program of the
NIH, NINDS (Alan P. Koretsky, Scientific Director), and FAPESP
(2006/05706-5, 2003/13399-7, 2005/56663-1).
NR 42
TC 20
Z9 22
U1 1
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD SEP 1
PY 2011
VL 58
IS 1
BP 75
EP 81
DI 10.1016/j.neuroimage.2011.06.030
PG 7
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 802ZC
UT WOS:000293548500010
PM 21708273
ER
PT J
AU Lubet, RA
Heckman, BM
De Flora, SL
Steele, VE
Crowell, JA
Juliana, MM
Grubbs, CJ
AF Lubet, Ronald A.
Heckman, Brandy M.
De Flora, Silvio L.
Steele, Vernon E.
Crowell, James A.
Juliana, M. Margaret
Grubbs, Clinton J.
TI Effects of 5,6-benzoflavone, indole-3-carbinol (I3C) and
diindolyimethane (DIM) on chemically-induced mammary carcinogenesis: Is
DIM a substitute for I3C?
SO ONCOLOGY REPORTS
LA English
DT Article
DE Ah receptors; 5,6-benzoflavone; indole-3-carbinol; diindolylmethane;
mammary cancer
ID DNA ADDUCT FORMATION; DIETARY INDOLE-3-CARBINOL; HYDROXYLASE-ACTIVITY;
BETA-NAPHTHOFLAVONE; CANCER CELLS; CHEMOPREVENTION; INHIBITION;
METABOLISM; MICE; RAT
AB The abilities of 5,6-benzoflavone (5,6-BF, a synthetic flavonoid), indole-3-carbinol (I3C, a plant derived product) or diindolylmethane (DIM, a condensation product of I3C) to alter the induction of mammary cancers induced by the carcinogens 7,12-dimethylbenzanthracene (DMBA) or N-methyl-N-nitrosourea (M NU) were evaluated. Interestingly, the first two agents act as aryl hydrocarbon receptor (AhR) agonists, while DIM does not. The agents were initially examined for their ability to inhibit DM BA-induced mammary carcinogenesis. Agents were administered for 14 days starting 7 days prior to a single dose of the carcinogen. Evaluated over an extensive range of doses (165, 550 and 1650 ppm in the diet), 5,6-BF caused a dose-dependent decrease of mammary cancers. In addition, 5,6-BF at closes of 1650 and 165 ppm in the diet blocked the induction of DMBA-induced DNA adducts in the mammary gland by approximately 85% and 45%, respectively. In contrast, DIM (180 or 20 mg/kg BW/day) failed to block induction of DMBA tumors. The effect of these agents on the promotion/progression phase of carcinogenesis using the MNU mammary cancer model was also determined. 5,6-BF (1650 or 165 ppm in the diet), I3C (180 or 60 mg/kg BW/day administered by gavage), or DIM (180 or 60 mg/kg BW/day by gavage) were initiated 5 days after the administration of MNU, and continually thereafter. 5,6-BF decreased MNU-induced mammary tumor multiplicity by 40-60%. I3C reduced tumor multiplicity at the high dose, while DIM at either dose had minimal effects on tumor multiplicity. Thus, 5,6-BE and I3C were highly effective against initiation of DMBA-induced mammary carcinogenesis, and were also effective against MNU-induced tumors during the promotion/progression phase of carcinogenesis. In contrast, DIM had minimal effects in either model; arguing that administration of DIM is not analogous to administration of I3C.
C1 [Lubet, Ronald A.] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Crowell, James A.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[De Flora, Silvio L.] Univ Genoa, Dept Hlth Sci, I-16132 Genoa, Italy.
[Juliana, M. Margaret] Univ Alabama, Chemoprevent Ctr, Birmingham, AL 35294 USA.
RP Lubet, RA (reprint author), NCI, Canc Prevent Div, NIH, Executive Plaza N,Suite 2110,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM lubetr@mail.nih.gov
FU NCI [N01-CN-75008, NO1-CN-43301]
FX The authors wish to thank Jeanne Hale, Mary Jo Cagle and Julie Gray for
editorial services. Also, thanks are expressed to Tom Morgan, Bonnie
Dillon and Brittany Cornelius for assistance with the animal studies.
This study was supported by NCI Master Agreements N01-CN-75008 and
NO1-CN-43301.
NR 32
TC 15
Z9 15
U1 0
U2 4
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1021-335X
J9 ONCOL REP
JI Oncol. Rep.
PD SEP
PY 2011
VL 26
IS 3
BP 731
EP 736
DI 10.3892/or.2011.1316
PG 6
WC Oncology
SC Oncology
GA 801GI
UT WOS:000293426100028
PM 21617870
ER
PT J
AU Schindler, CW
Cogan, ES
Thorndike, EB
Panlilio, LV
AF Schindler, Charles W.
Cogan, Elizabeth S.
Thorndike, Eric B.
Panlilio, Leigh V.
TI Rapid delivery of cocaine facilitates acquisition of self-administration
in rats: An effect masked by paired stimuli
SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
LA English
DT Article
DE Cocaine; Self-administration; Infusion duration; Acquisition; Rat
ID INTRAVENOUS-INJECTION SPEED; DOPAMINE TRANSPORTER; RHESUS-MONKEYS;
REINFORCING STRENGTH; HUMANS; NICOTINE; SENSITIZATION; MAINTENANCE;
INFUSION; DEPEND
AB In general, faster infusions of cocaine are more likely to support behavior related to abuse than are slower infusions. However, some studies of cocaine self-administration in rats have failed to support this finding, possibly because the effect was masked by other factors. One such factor may be the pairing of a stimulus with the infusion, a procedure that is known to facilitate acquisition of drug self-administration. We compared fast and slow infusions by allowing groups of rats to acquire cocaine self-administration at a dose of 1 mg/kg/infusion, delivered over different durations (1.8 or 100s). Two groups were trained with either short or long infusions paired with a visual stimulus change ( lights off), and two other groups were trained with short or long durations but with no stimulus change. Both groups trained with a paired stimulus acquired cocaine self-administration. With no stimulus change, the rats trained with the 1.8-s infusion acquired cocaine self-administration at a rate comparable to the two groups that were trained with a paired stimulus. However, most rats in the group trained with the 100-s infusion that was not accompanied by a stimulus change failed to acquire cocaine self-administration. The stimulus itself did not support responding. These results indicate that infusing a given dose of cocaine over a longer duration reduces its ability to support self-administration, but drug-paired stimuli can partially mask this effect by enhancing the effectiveness of slow infusions. Published by Elsevier Inc.
C1 [Schindler, Charles W.; Cogan, Elizabeth S.; Thorndike, Eric B.; Panlilio, Leigh V.] NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch, DHHS,NIH,Intramural Res Program, Baltimore, MD 21224 USA.
RP Schindler, CW (reprint author), NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch, DHHS,NIH,Intramural Res Program, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM cschindl@helix.nih.gov
FU NIH, NIDA
FX This research was supported by the Intramural Research Program of the
NIH, NIDA.
NR 43
TC 8
Z9 8
U1 0
U2 0
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 2011
VL 99
IS 3
BP 301
EP 306
DI 10.1016/j.pbb.2011.05.005
PG 6
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA 800OL
UT WOS:000293371100002
PM 21600912
ER
PT J
AU Winter, JC
Amorosi, DJ
Rice, KC
Cheng, KJ
Yu, AM
AF Winter, J. C.
Amorosi, D. J.
Rice, Kenner C.
Cheng, Kejun
Yu, Ai-Ming
TI Stimulus control by 5-methoxy-N,N-dimethyltryptamine in wild-type and
CYP2D6-humanized mice
SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
LA English
DT Article
DE Drug-induced stimulus control; Harmaline;
5-methoxy-N,N-dimethyltryptamine; Drug interact on; CYP2D6; Humanized
mice
ID DISCRIMINATIVE STIMULI; PHARMACOLOGICAL ACTIONS; CYTOCHROME-P450 2D6;
MONOAMINE-OXIDASE; HUMANIZED MOUSE; BETA-CARBOLINES; LSD; HALLUCINOGENS;
BUFOTENINE; N,N-DIMETHYLTRYPTAMINE
AB In previous studies we have observed that, in comparison with wild type mice, Tg-CYP2D6 mice have increased serum levels of bufotenine [5-hydroxy-N,N-dimethyltryptamine] following the administration of 5-MeO-DMT. Furthermore, following the injection of 5-MeO-DMT, harmaline was observed to increase serum levels of bufotenine and 5-MeO-DMT in both wild-type and Tg-CYP2D6 mice. In the present investigation, 5-MeO-DMT-induced stimulus control was established in wild-type and Tg-CYP2D6 mice. The two groups did not differ in their rate of acquisition of stimulus control. When tested with bufotenine, no 5-MeO-DMT-appropriate responding was observed. In contrast, the more lipid soluble analog of bufotenine, acetylbufotenine, was followed by an intermediate level of responding. The combination of harmaline with 5-MeO-DMT yielded a statistically significant increase in 5-MeO-DMT-appropriate responding in Tg-CYP2D6 mice; a comparable increase occurred in wild-type mice. In addition, it was noted that harmaline alone was followed by a significant degree of 5-MeO-DMT-appropriate responding in Tg-CYP2D6 mice. It is concluded that wild-type and Tg-CYPD2D6 mice do not differ in terms of acquisition of stimulus control by 5-MeO-DMT or in their response to bufotenine and acetylbufotenine. In both groups of mice, harmaline was found to enhance the stimulus effects of 5-MeO-DMT. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Winter, J. C.; Amorosi, D. J.] SUNY Buffalo, Sch Med & Biomed Sci, Dept Pharmacol & Toxicol, Buffalo, NY 14214 USA.
[Yu, Ai-Ming] SUNY Buffalo, Sch Pharm & Pharmaceut Sci, Dept Pharmaceut Sci, Buffalo, NY 14214 USA.
[Rice, Kenner C.; Cheng, Kejun] NIDA, Chem Biol Res Branch, Rockville, MD 20892 USA.
RP Winter, JC (reprint author), SUNY Buffalo, Sch Med & Biomed Sci, Dept Pharmacol & Toxicol, 102 Farber Hall, Buffalo, NY 14214 USA.
EM jcwinter@buffalo.edu
FU National Institute on Drug Abuse [DA03385, DA021172]; National
Institutes of Health
FX This study was supported in part by award number DA03385 [J.C. Winter]
and DA021172 [A-M Yu] from the National Institute on Drug Abuse, and
National Institutes of Health.
NR 36
TC 6
Z9 7
U1 0
U2 8
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 2011
VL 99
IS 3
BP 311
EP 315
DI 10.1016/j.pbb.2011.05.015
PG 5
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA 800OL
UT WOS:000293371100004
PM 21624387
ER
PT J
AU Deveney, CM
Kim, P
Brotman, MA
Pine, DS
Leibenluft, E
AF Deveney, Christen M.
Kim, Pilyoung
Brotman, Melissa A.
Pine, Daniel S.
Leibenluft, Ellen
TI NEUROIMAGING EXAMINATIONS OF INHIBITORY PROCESSES IN YOUTHS WITH SEVERE
MOOD DYSREGULATION AND BIPOLAR DISORDER
SO PSYCHOPHYSIOLOGY
LA English
DT Meeting Abstract
CT 51st Annual Meeting of the Society-of-Psychophysiological-Research
CY SEP 14-18, 2011
CL Boston, MA
SP Soc Psychophysiol Res
C1 [Deveney, Christen M.; Kim, Pilyoung; Brotman, Melissa A.; Pine, Daniel S.; Leibenluft, Ellen] NIMH, NIH, HHS, Bethesda, MD USA.
RI Brotman, Melissa/H-7409-2013
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0048-5772
J9 PSYCHOPHYSIOLOGY
JI Psychophysiology
PD SEP
PY 2011
VL 48
SU 1
SI SI
BP S13
EP S13
PG 1
WC Psychology, Biological; Neurosciences; Physiology; Psychology;
Psychology, Experimental
SC Psychology; Neurosciences & Neurology; Physiology
GA 800TE
UT WOS:000293389200071
ER
PT J
AU Goldman, DJ
Sponheim, SR
Van Meerten, N
Skorheim, MK
Cuthbert, BN
AF Goldman, Daniel J.
Sponheim, Scott R.
Van Meerten, Nicolaas
Skorheim, Mallory K.
Cuthbert, Bruce N.
TI EMOTION-MODULATED STARTLE REACTIVITY IN COMBAT VETERANS WITH AND WITHOUT
PTSD AND BLAST-RELATED MILD TRAUMATIC BRAIN INJURY
SO PSYCHOPHYSIOLOGY
LA English
DT Meeting Abstract
CT 51st Annual Meeting of the Society-of-Psychophysiological-Research
CY SEP 14-18, 2011
CL Boston, MA
SP Soc Psychophysiol Res
DE startle blink; PTSD; mtbi
C1 [Goldman, Daniel J.; Sponheim, Scott R.] Univ Minnesota, Minneapolis, MN 55455 USA.
[Sponheim, Scott R.; Van Meerten, Nicolaas; Skorheim, Mallory K.] Minneapolis VAHCS, Minneapolis, MN USA.
[Cuthbert, Bruce N.] NIMH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0048-5772
J9 PSYCHOPHYSIOLOGY
JI Psychophysiology
PD SEP
PY 2011
VL 48
SU 1
SI SI
BP S110
EP S110
PG 1
WC Psychology, Biological; Neurosciences; Physiology; Psychology;
Psychology, Experimental
SC Psychology; Neurosciences & Neurology; Physiology
GA 800TE
UT WOS:000293389200613
ER
PT J
AU Nielsen, L
AF Nielsen, Lisbeth
TI EMOTION REGULATION AND EMOTION-COGNITION INTERACTIONS IN NORMAL AGING
SO PSYCHOPHYSIOLOGY
LA English
DT Meeting Abstract
CT 51st Annual Meeting of the Society-of-Psychophysiological-Research
CY SEP 14-18, 2011
CL Boston, MA
SP Soc Psychophysiol Res
C1 [Nielsen, Lisbeth] NIA, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0048-5772
J9 PSYCHOPHYSIOLOGY
JI Psychophysiology
PD SEP
PY 2011
VL 48
SU 1
SI SI
BP S2
EP S2
PG 1
WC Psychology, Biological; Neurosciences; Physiology; Psychology;
Psychology, Experimental
SC Psychology; Neurosciences & Neurology; Physiology
GA 800TE
UT WOS:000293389200002
ER
PT J
AU Robinson, OJ
Overstreet, C
Charney, DR
Letkiewicz, A
Vytal, K
Grillon, C
AF Robinson, Oliver J.
Overstreet, Cassie
Charney, Danielle R.
Letkiewicz, Allison
Vytal, Katherine
Grillon, Christian
TI THE EFFECTS OF THREAT OF SHOCK ON EMOTIONAL FACE PROCESSING
SO PSYCHOPHYSIOLOGY
LA English
DT Meeting Abstract
CT 51st Annual Meeting of the Society-of-Psychophysiological-Research
CY SEP 14-18, 2011
CL Boston, MA
SP Soc Psychophysiol Res
C1 [Robinson, Oliver J.; Overstreet, Cassie; Charney, Danielle R.; Letkiewicz, Allison; Vytal, Katherine; Grillon, Christian] NIMH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0048-5772
J9 PSYCHOPHYSIOLOGY
JI Psychophysiology
PD SEP
PY 2011
VL 48
SU 1
SI SI
BP S7
EP S8
PG 2
WC Psychology, Biological; Neurosciences; Physiology; Psychology;
Psychology, Experimental
SC Psychology; Neurosciences & Neurology; Physiology
GA 800TE
UT WOS:000293389200037
ER
PT J
AU Vytal, K
Cornwell, B
Robinson, OJ
Grillon, C
AF Vytal, Katherine
Cornwell, Brian
Robinson, Oliver J.
Grillon, Christian
TI RECIPROCAL INTERACTIONS BETWEEN ANXIETY AND COGNITION
SO PSYCHOPHYSIOLOGY
LA English
DT Meeting Abstract
CT 51st Annual Meeting of the Society-of-Psychophysiological-Research
CY SEP 14-18, 2011
CL Boston, MA
SP Soc Psychophysiol Res
C1 [Vytal, Katherine; Cornwell, Brian; Robinson, Oliver J.; Grillon, Christian] NIMH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0048-5772
J9 PSYCHOPHYSIOLOGY
JI Psychophysiology
PD SEP
PY 2011
VL 48
SU 1
SI SI
BP S8
EP S8
PG 1
WC Psychology, Biological; Neurosciences; Physiology; Psychology;
Psychology, Experimental
SC Psychology; Neurosciences & Neurology; Physiology
GA 800TE
UT WOS:000293389200039
ER
PT J
AU White, SF
Marsh, AA
Fowler, KA
Schechter, JC
Sinclair, S
Pine, DS
Blair, RJR
AF White, Stuart F.
Marsh, Abigail A.
Fowler, Katherine A.
Schechter, Julia C.
Sinclair, Stephen
Pine, Daniel S.
Blair, R. J. R.
TI A TEST OF CAUSAL HYPOTHESES OF PSYCHOPATHIC TRAITS: REDUCED EMOTIONAL
RESPONSIVENESS OR ANOMALOUS ATTENTIONAL CONTROL?
SO PSYCHOPHYSIOLOGY
LA English
DT Meeting Abstract
CT 51st Annual Meeting of the Society-of-Psychophysiological-Research
CY SEP 14-18, 2011
CL Boston, MA
SP Soc Psychophysiol Res
C1 [White, Stuart F.; Fowler, Katherine A.; Sinclair, Stephen; Pine, Daniel S.; Blair, R. J. R.] NIMH, NIH, HHS, Bethesda, MD USA.
[Marsh, Abigail A.] Georgetown Univ, Washington, DC 20057 USA.
[Schechter, Julia C.] Emory Univ, Atlanta, GA 30322 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0048-5772
J9 PSYCHOPHYSIOLOGY
JI Psychophysiology
PD SEP
PY 2011
VL 48
SU 1
SI SI
BP S13
EP S13
PG 1
WC Psychology, Biological; Neurosciences; Physiology; Psychology;
Psychology, Experimental
SC Psychology; Neurosciences & Neurology; Physiology
GA 800TE
UT WOS:000293389200069
ER
PT J
AU Saradhi, UVRV
Gupta, SV
Chiu, M
Wang, J
Ling, YH
Liu, ZF
Newman, DJ
Covey, JM
Kinghorn, AD
Marcucci, G
Lucas, DM
Grever, MR
Phelps, MA
Chan, KK
AF Saradhi, U. V. R. Vijaya
Gupta, Sneha V.
Chiu, Ming
Wang, Jiang
Ling, Yonghua
Liu, Zhongfa
Newman, David J.
Covey, Joseph M.
Kinghorn, A. Douglas
Marcucci, Guido
Lucas, David M.
Grever, Michael R.
Phelps, Mitch A.
Chan, Kenneth K.
TI Characterization of Silvestrol Pharmacokinetics in Mice Using Liquid
Chromatography-Tandem Mass Spectrometry
SO AAPS JOURNAL
LA English
DT Article
DE liquid chromatography-tandem mass spectrometry; mouse plasma;
pharmacokinetics; silvestrol
ID AGLAIA; (-)-SILVESTROL; (-)-EPISILVESTROL; ROCAGLAMIDE; DERIVATIVES
AB A sensitive and specific liquid chromatography-tandem mass spectrometry method was developed and validated for the quantification of the plant natural product silvestrol in mice, using ansamitocin P-3 as the internal standard. The method was validated in plasma with a lower limit of quantification of 1 ng/mL, accuracy ranging from 87 to 114%, and precision (coefficient of variation) below 15%. The validated method was used to characterize pharmacokinetics in C57BL/6 mice and metabolism in mouse, human and rat plasma, and liver microsomes. Mice were dosed with silvestrol formulated in hydroxypropyl-beta-cyclodextrin via intravenous, intraperitoneal, and oral routes followed by blood sampling up to 24 h. Intraperitoneal systemic availability was 100%, but oral administration resulted in only 1.7% bioavailability. Gradual degradation of silvestrol was observed in mouse and human plasma, with approximately 60% of the parent drug remaining after 6 h. In rat plasma, however, silvestrol was completely converted to silvestric acid (SA) within 10 min. Evaluation in microsomes provided further evidence that the main metabolite formed was SA, which subsequently showed no cytotoxic or cytostatic activity in a silvestrol-sensitive lymphoblastic cell line. The ability of the analytical assay to measure tissue levels of silvestrol was evaluated in liver, brain, kidney, and spleen. Results indicated the method was capable of accurately measuring tissue levels of silvestrol and suggested it has a relatively low distribution to brain. Together, these data suggest an overall favorable pharmacokinetic profile of silvestrol in mice and provide crucial information for its continued development toward potential clinical testing.
C1 [Saradhi, U. V. R. Vijaya; Gupta, Sneha V.; Chiu, Ming; Wang, Jiang; Ling, Yonghua; Liu, Zhongfa; Kinghorn, A. Douglas; Marcucci, Guido; Lucas, David M.; Phelps, Mitch A.; Chan, Kenneth K.] Ohio State Univ, Coll Pharm, Columbus, OH 43210 USA.
[Newman, David J.; Covey, Joseph M.] NCI, Rockville, MD USA.
[Marcucci, Guido; Lucas, David M.; Grever, Michael R.; Phelps, Mitch A.; Chan, Kenneth K.] Ohio State Univ, Coll Med, Columbus, OH 43210 USA.
RP Phelps, MA (reprint author), Ohio State Univ, Coll Pharm, 500 W 12th Ave, Columbus, OH 43210 USA.
EM mitch.phelps@osumc.edu; chan.56@osu.edu
RI Liu, Zhongfa/G-8549-2013; Phelps, Mitch/H-3941-2013; Lucas,
David/E-3555-2011;
OI Phelps, Mitch/0000-0002-1615-5280; Kinghorn, A.
Douglas/0000-0002-6647-8707
FU U.S. National Cancer Institute [N01-CM-52205, P01-CA125066,
P50-CA140158]; Ohio State University Comprehensive Cancer Center
[P30-CA016058-35]
FX This work was supported by the U.S. National Cancer Institute [Contract
N01-CM-52205 to KKC, P01-CA125066 to ADK, SPORE P50-CA140158 to MRG, and
The Ohio State University Comprehensive Cancer Center Core Grant
(P30-CA016058-35) supporting the Experimental Therapeutics Program and
Pharmacoanalytical Shared Resource].
NR 17
TC 18
Z9 18
U1 0
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1550-7416
J9 AAPS J
JI AAPS J.
PD SEP
PY 2011
VL 13
IS 3
BP 347
EP 356
DI 10.1208/s12248-011-9273-x
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 798ES
UT WOS:000293186000006
PM 21499689
ER
PT J
AU Lubin, JH
Muscat, J
Gaudet, MM
Olshan, AF
Curado, MP
Dal Maso, L
Wunsch, V
Sturgis, EM
Szeszenia-Dabrowska, N
Castellsague, X
Zhang, ZF
Smith, E
Fernandez, L
Matos, E
Franceschi, S
Fabianova, E
Rudnai, P
Purdue, MP
Mates, D
Wei, QY
Herrero, R
Kelsey, K
Morgenstern, H
Shangina, O
Koifman, S
Lissowska, J
Levi, F
Daudt, AW
Neto, JE
Chen, C
Lazarus, P
Winn, DM
Schwartz, SM
Boffetta, P
Brennan, P
Menezes, A
La Vecchia, C
McClean, M
Talamini, R
Rajkumar, T
Hayes, RB
Hashibe, M
AF Lubin, Jay H.
Muscat, Joshua
Gaudet, Mia M.
Olshan, Andrew F.
Curado, Maria Paula
Dal Maso, Luigino
Wuensch-Filho, Victor
Sturgis, Erich M.
Szeszenia-Dabrowska, Neonilia
Castellsague, Xavier
Zhang, Zuo-Feng
Smith, Elaine
Fernandez, Leticia
Matos, Elena
Franceschi, Silvia
Fabianova, Eleonora
Rudnai, Peter
Purdue, Mark P.
Mates, Dana
Wei, Qingyi
Herrero, Rolando
Kelsey, Karl
Morgenstern, Hal
Shangina, Oxana
Koifman, Sergio
Lissowska, Jolanta
Levi, Fabio
Daudt, Alexander W.
Eluf Neto, Jose
Chen, Chu
Lazarus, Philip
Winn, Deborah M.
Schwartz, Stephen M.
Boffetta, Paolo
Brennan, Paul
Menezes, Ana
La Vecchia, Carlo
McClean, Michael
Talamini, Renato
Rajkumar, Thangarajan
Hayes, Richard B.
Hashibe, Mia
TI An examination of male and female odds ratios by BMI, cigarette smoking,
and alcohol consumption for cancers of the oral cavity, pharynx, and
larynx in pooled data from 15 case-control studies
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Alcohol consumption; Cigarette smoking; Interactions; Odds ratio models
ID BODY-MASS INDEX; HUMAN-PAPILLOMAVIRUS INFECTION; SQUAMOUS-CELL
CARCINOMA; NECK-CANCER; OROPHARYNGEAL CANCER; UNITED-STATES;
INTERNATIONAL HEAD; INHANCE CONSORTIUM; HPV INFECTION; RISK
AB Greater tobacco smoking and alcohol consumption and lower body mass index (BMI) increase odds ratios (OR) for oral cavity, oropharyngeal, hypopharyngeal, and laryngeal cancers; however, there are no comprehensive sex-specific comparisons of ORs for these factors.
We analyzed 2,441 oral cavity (925 women and 1,516 men), 2,297 oropharynx (564 women and 1,733 men), 508 hypopharynx (96 women and 412 men), and 1,740 larynx (237 women and 1,503 men) cases from the INHANCE consortium of 15 head and neck cancer case-control studies. Controls numbered from 7,604 to 13,829 subjects, depending on analysis. Analyses fitted linear-exponential excess ORs models.
ORs were increased in underweight (< 18.5 BMI) relative to normal weight (18.5-24.9) and reduced in overweight and obese categories (a parts per thousand yen25 BMI) for all sites and were homogeneous by sex. ORs by smoking and drinking in women compared with men were significantly greater for oropharyngeal cancer (p < 0.01 for both factors), suggestive for hypopharyngeal cancer (p = 0.05 and p = 0.06, respectively), but homogeneous for oral cavity (p = 0.56 and p = 0.64) and laryngeal (p = 0.18 and p = 0.72) cancers.
The extent that OR modifications of smoking and drinking by sex for oropharyngeal and, possibly, hypopharyngeal cancers represent true associations, or derive from unmeasured confounders or unobserved sex-related disease subtypes (e.g., human papillomavirus-positive oropharyngeal cancer) remains to be clarified.
C1 [Lubin, Jay H.; Purdue, Mark P.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Muscat, Joshua; Lazarus, Philip] Penn State Coll Med, Hershey, PA USA.
[Gaudet, Mia M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Olshan, Andrew F.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
[Curado, Maria Paula; Franceschi, Silvia; Boffetta, Paolo; Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France.
[Dal Maso, Luigino; Talamini, Renato] Aviano Canc Ctr, Epidemiol & Biostat Unit, I-33081 Aviano, Italy.
[Wuensch-Filho, Victor; Eluf Neto, Jose] Univ Sao Paulo, Sao Paulo, Brazil.
[Sturgis, Erich M.; Wei, Qingyi] UT MD Anderson Canc Ctr, Houston, TX USA.
[Szeszenia-Dabrowska, Neonilia] Inst Occupat Med, Lodz, Poland.
[Castellsague, Xavier] CIBER ESP, IDIBELL, ICO, Barcelona, Spain.
[Zhang, Zuo-Feng] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA.
[Smith, Elaine] Univ Iowa, Coll Publ Hlth, Iowa City, IA USA.
[Fernandez, Leticia] Inst Oncol & Radiobiol, Havana, Cuba.
[Matos, Elena] Univ Buenos Aires, Inst Oncol Angel H Roffo, Buenos Aires, DF, Argentina.
[Fabianova, Eleonora] Specialized State Hlth Inst, Banska Bystrica, Slovakia.
[Rudnai, Peter] Natl Inst Environm Hlth, Budapest, Hungary.
[Mates, Dana] Inst Publ Hlth, Dept Occupat Hlth, Bucharest, Romania.
[Herrero, Rolando] Inst Invest Epidemiol, San Jose, Costa Rica.
[Kelsey, Karl] Brown Univ, Bio Med Ctr Environm Hlth & Technol, Providence, RI 02912 USA.
[Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA.
[Morgenstern, Hal] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Shangina, Oxana] Russian Acad Med Sci, Canc Res Ctr, Moscow, Russia.
[Koifman, Sergio] Fundacao Oswaldo Cruz, Escola Nacl Saude Publ, Rio De Janeiro, Brazil.
[Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[Levi, Fabio] Univ Lausanne, Inst Med Sociale & Prevent, Lausanne, Switzerland.
[Daudt, Alexander W.] Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil.
[Chen, Chu; Schwartz, Stephen M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Winn, Deborah M.] NCI, Div Canc Control & Populat Sci, Rockville, MD 20852 USA.
[Boffetta, Paolo] Mt Sinai Sch Med, New York, NY USA.
[Menezes, Ana] Univ Fed Pelotas, Pelotas, Brazil.
[La Vecchia, Carlo] Ist Ric Farmacol Mario Negri, Milan, Italy.
[La Vecchia, Carlo] Univ Milan, Milan, Italy.
[McClean, Michael] Boston Univ, Sch Publ Hlth, Boston, MA USA.
[Rajkumar, Thangarajan] Canc Inst WIA, Dept Mol Oncol, Madras, Tamil Nadu, India.
[Hayes, Richard B.] NYU, Langone Med Ctr, Div Epidemiol, New York, NY USA.
[Hashibe, Mia] Univ Utah, Huntsman Canc Inst, Dept Family & Prevent Med, Salt Lake City, UT USA.
RP Lubin, JH (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Rockville, MD 20852 USA.
EM lubinj@mail.nih.gov
RI Sriwisit, Sukhumaphorn/G-1405-2011; Wunsch Filho, Victor/C-4475-2012;
Inca, Inct/K-2204-2013; Epidemiologicas, Centro de pesquisas
/D-4561-2013; Menezes, Ana/G-7266-2012; Szeszenia-Dabrowska,
Neonila/F-7190-2010; McClean, Michael/J-2934-2015; Castellsague Pique,
Xavier/N-5795-2014; Eluf-Neto, Jose/B-2522-2009; Purdue,
Mark/C-9228-2016; Curado, Maria Paula/M-6200-2013;
OI Castellsague Pique, Xavier/0000-0002-0802-3595; Eluf-Neto,
Jose/0000-0001-7504-2115; Purdue, Mark/0000-0003-1177-3108; Curado,
Maria Paula/0000-0001-8172-2483; mates, dana/0000-0002-6219-9807;
Lissowska, Jolanta/0000-0003-2695-5799; dal maso,
luigino/0000-0001-6163-200X; La Vecchia, Carlo/0000-0003-1441-897X;
Hayes, Richard/0000-0002-0918-661X
FU National Institutes of Health; National Cancer Institute, Department of
Health and Human Services; National Institute of Environmental Health
Sciences [P30ES10126]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health and the National Cancer Institute,
Department of Health and Human Services and by a grant from the National
Institute of Environmental Health Sciences (P30ES10126).
NR 62
TC 14
Z9 14
U1 3
U2 11
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD SEP
PY 2011
VL 22
IS 9
BP 1217
EP 1231
DI 10.1007/s10552-011-9792-x
PG 15
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 799OO
UT WOS:000293296200001
PM 21744095
ER
PT J
AU Andreotti, G
Liu, EJ
Gao, YT
Safaeian, M
Rashid, A
Shen, MC
Wang, BS
Deng, J
Han, TQ
Zhang, BH
Hsing, AW
AF Andreotti, Gabriella
Liu, Enju
Gao, Yu-Tang
Safaeian, Mahboobeh
Rashid, Asif
Shen, Ming-Chang
Wang, Bin-Shen
Deng, Jie
Han, Tian-Quian
Zhang, Bai-He
Hsing, Ann W.
TI Medical history and the risk of biliary tract cancers in Shanghai,
China: implications for a role of inflammation
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Biliary tract cancer; Biliary stones; Medical history; Inflammation;
China
ID NITRIC-OXIDE; GALLBLADDER CARCINOGENESIS; CHRONIC CHOLECYSTITIS;
INSULIN-RESISTANCE; GALL-BLADDER; CARCINOMA; LESIONS; EXPRESSION;
GALLSTONES; INFECTION
AB Several lines of evidence suggest that inflammation may play a role in the etiology of biliary tract cancers. To examine further the role of inflammation, we evaluated the associations between self-reported inflammatory-related medical conditions and the risk of biliary tract cancers in a population-based case-control study in Shanghai, China. Our analysis included 368 gallbladder cancer cases, 191 bile duct cancer cases, 68 ampulla of Vater cancer cases, and 959 healthy subjects. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for biliary tract cancers in relation to six inflammation-related conditions. Gallbladder cancer was significantly associated with cholecystitis occurring at least 5 years prior to interview (OR = 1.7, 95% CI 1.1-2.9). Even though biliary stones did not significantly modify the associations between cholecystitis and gallbladder cancer, 90% of the gallbladder cancer cases with cholecystitis also had biliary stones, indicating that stones likely play an important role in the link between cholecystitis and gallbladder cancer. Among subjects who smoked and drank alcohol, a history of gastric (OR = 4.3, 95% CI 1.2-15.0) or duodenal ulcers (OR = 3.7, 1.2-12.0) was associated with an excess risk of gallbladder cancer. Although the mechanisms are unclear, our results further support the role for inflammation in the etiology of biliary tract cancers.
C1 [Andreotti, Gabriella; Safaeian, Mahboobeh; Hsing, Ann W.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Liu, Enju; Gao, Yu-Tang; Deng, Jie] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Rashid, Asif] Univ Texas Houston, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Shen, Ming-Chang] Fudan Univ, Shanghai Tumor Hosp, Shanghai 200433, Peoples R China.
[Wang, Bin-Shen] Fudan Univ, Zhong Shan Hosp, Shanghai 200433, Peoples R China.
[Han, Tian-Quian] Shanghai Med Univ 2, Rui Jin Hosp, Dept Surg, Shanghai, Peoples R China.
[Zhang, Bai-He] Shanghai Second Mil Univ, Inst E Hepatobiliary Surg, Shanghai, Peoples R China.
RP Andreotti, G (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8011,MSC 7240, Bethesda, MD 20892 USA.
EM andreotg@mail.nih.gov
RI liu, enju/F-4062-2010
FU National Institute of Health, National Cancer Institute, Division of
Cancer Epidemiology and Genetics, USA
FX We thank the collaborating surgeons and pathologists in Shanghai for
assistance in patient recruitment and pathology review; Chia-Rong Cheng,
Lu Sun, and Kai Wu of the Shanghai Cancer Institute for coordinating
data and specimen collection; and Shelley Niwa of Westat for support
with study and data management. The study was funded by the Intramural
Research Program of the National Institute of Health, National Cancer
Institute, Division of Cancer Epidemiology and Genetics, USA.
NR 29
TC 8
Z9 9
U1 0
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD SEP
PY 2011
VL 22
IS 9
BP 1289
EP 1296
DI 10.1007/s10552-011-9802-z
PG 8
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 799OO
UT WOS:000293296200007
PM 21744094
ER
PT J
AU Volpe, A
Cadeddu, JA
Cestari, A
Gill, IS
Jewett, MAS
Joniau, S
Kirkali, Z
Marberger, M
Patard, JJ
Staehler, M
Uzzo, RG
AF Volpe, Alessandro
Cadeddu, Jeffrey A.
Cestari, Andrea
Gill, Inderbir S.
Jewett, Michael A. S.
Joniau, Steven
Kirkali, Ziya
Marberger, Michael
Patard, Jean Jacques
Staehler, Michael
Uzzo, Robert G.
TI Contemporary Management of Small Renal Masses
SO EUROPEAN UROLOGY
LA English
DT Review
DE Carcinoma, renal cell; Cryoablation; Nephron-sparing surgery; Partial
nephrectomy; Renal mass; Renal tumour biopsy; Surveillance; Thermal
ablation
ID LAPAROSCOPIC PARTIAL NEPHRECTOMY; NEPHRON-SPARING SURGERY; INTENSITY
FOCUSED ULTRASOUND; NORMAL CONTRALATERAL KIDNEY; RADIO-FREQUENCY
ABLATION; PERCUTANEOUS RADIOFREQUENCY ABLATION; WARM ISCHEMIA TIME; CELL
CARCINOMA; ACTIVE SURVEILLANCE; NATURAL-HISTORY
AB Context: An increasing number of small renal masses (SRMs) with heterogeneous histology and clinical behaviour are being detected with modern radiologic imaging. Although surgical removal is the standard of care for small renal tumours, alternative minimally invasive and conservative treatment options are possible in selected patients with shorter life expectancy.
Objective: To systematically review indications, techniques, and outcomes of surgical and conservative treatments of SRMs.
Evidence acquisition: A literature search of English-language publications was performed using the Medline database from January 2000 to February 2011 using the terms renal mass and renal carcinoma in conjunction with the evaluated management options. The articles that provided the highest level of evidence were selected with the consensus of all the authors and reviewed.
Evidence synthesis: Only one randomised controlled trial comparing the results of elective nephron-sparing surgery and radical nephrectomy for low-stage renal tumours is available. Few comparative studies of different treatment options for SRMs have been published. The assessment of oncologic outcomes is therefore based mainly on observational studies. Most series of nonsurgical therapies have strong selection biases and relatively short follow-up. Treatment selection is based on the clinical and histologic characteristics of SRMs, on patient age and comorbidities, and on personal preferences and experience of the urologist.
Conclusions: Partial nephrectomy (PN) is the standard treatment for solitary SRMs whenever it is technically feasible. Laparoscopic PN is an alternative to open PN in experienced hands. The rationale of ablative treatments is to treat incidental cortical SRMs in patients at high surgical risk with potentially reduced morbidity. Active surveillance is considered an appropriate strategy for the elderly or for patients with significant comorbidity who have a shorter life expectancy. Percutaneous biopsies are increasingly being used to establish histology of SRMs and support treatment decisions, especially for patients who are candidates for nonsurgical treatment. (C) 2011 Published by Elsevier B. V. on behalf of European Association of Urology.
C1 [Volpe, Alessandro] Univ Piemonte Orientale, Maggiore Carita Hosp, Div Urol, I-28100 Novara, Italy.
[Cadeddu, Jeffrey A.] Univ Texas SW Med Ctr Dallas, Dept Urol, Dallas, TX 75390 USA.
[Cestari, Andrea] Univ Vita Salute, Hosp San Raffaele, Dept Urol, Milan, Italy.
[Gill, Inderbir S.] Univ So Calif, Keck Sch Med, USC Inst Urol, Los Angeles, CA 90033 USA.
[Jewett, Michael A. S.] Univ Toronto, Princess Margaret Hosp, Dept Surg & Surg Oncol, Div Urol, Toronto, ON M5S 1A1, Canada.
[Jewett, Michael A. S.] Univ Toronto, Univ Hlth Network, Toronto, ON M5S 1A1, Canada.
[Joniau, Steven] Katholieke Univ Leuven Hosp, Dept Urol, Louvain, Belgium.
[Kirkali, Ziya] NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD USA.
[Marberger, Michael] Med Univ Vienna, Dept Urol, Vienna, Austria.
[Patard, Jean Jacques] Univ Paris 11, Bicetre Hosp, Dept Urol, Paris, France.
[Staehler, Michael] Univ Munich, Klinikum Grosshadern, Dept Urol, D-8000 Munich, Germany.
[Uzzo, Robert G.] Fox Chase Canc Ctr, Dept Urol Oncol, Philadelphia, PA 19111 USA.
RP Volpe, A (reprint author), Univ Piemonte Orientale, Maggiore Carita Hosp, Div Urol, Corso Mazzini 18, I-28100 Novara, Italy.
EM alessandro.volpe@med.unipmn.it
RI Joniau, Steven/K-7655-2013
OI Joniau, Steven/0000-0003-3195-9890
NR 134
TC 90
Z9 92
U1 0
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0302-2838
J9 EUR UROL
JI Eur. Urol.
PD SEP
PY 2011
VL 60
IS 3
BP 501
EP 515
DI 10.1016/j.eururo.2011.05.044
PG 15
WC Urology & Nephrology
SC Urology & Nephrology
GA 799JN
UT WOS:000293283100029
PM 21664040
ER
PT J
AU Nguyen, CM
Levy, AJ
AF Nguyen, Chien M.
Levy, Alan J.
TI Mechanics of interface failure in the trilayer elastic composite
SO INTERNATIONAL JOURNAL OF SOLIDS AND STRUCTURES
LA English
DT Article
DE Debonding; Layers; Interface; Integral equation; Cohesion;
Imperfections; Bifurcation; Elasticity
ID FRP-CONCRETE INTERFACE; RC BEAMS; DECOHESION; FRACTURE; DELAMINATION;
SUBSTRATE; BEHAVIOR; CRACKING; CONTACT; PLATE
AB An exact analysis of the mechanics of interface failure is presented for a trilayer composite system consisting of geometrically and materially distinct linear elastic layers separated by straight nonlinear, uniform and nonuniform decohesive interfaces. The technical significance of this system stems from its utility in representing two slabs joined together by a third adhesive layer whose thickness cannot be neglected. The formulation, based on exact infinitesimal strain elasticity solutions for rectangular domains, employs a methodology recently developed by the authors to investigate both solitary defect as well as multiple defect interaction problems in layered systems under arbitrary loading. Interfacial integral equations, governing the normal and tangential displacement jump components at the interfaces, are solved for the uniformly loaded trilayer system. Interfacial defects, taken in the form of interface perturbations and nonbonded portions of interface, are modeled by coordinate dependent interface strengths. They are examined in a variety of configurations chosen so as to shed light on the various interfacial failure mechanisms active in layered systems. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Levy, Alan J.] Syracuse Univ, Dept Mech & Aerosp Engn, Syracuse, NY 13244 USA.
[Nguyen, Chien M.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Levy, AJ (reprint author), Syracuse Univ, Dept Mech & Aerosp Engn, Syracuse, NY 13244 USA.
EM ajlevy@syr.edu
NR 30
TC 3
Z9 3
U1 4
U2 9
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0020-7683
J9 INT J SOLIDS STRUCT
JI Int. J. Solids Struct.
PD SEP 1
PY 2011
VL 48
IS 18
BP 2467
EP 2484
DI 10.1016/j.ijsolstr.2011.04.018
PG 18
WC Mechanics
SC Mechanics
GA 798JN
UT WOS:000293202100003
ER
PT J
AU Benson, JF
Hostetler, JA
Onorato, DP
Johnson, WE
Roelke, ME
O'Brien, SJ
Jansen, D
Oli, MK
AF Benson, John F.
Hostetler, Jeffrey A.
Onorato, David P.
Johnson, Warren E.
Roelke, Melody E.
O'Brien, Stephen J.
Jansen, Deborah
Oli, Madan K.
TI Intentional genetic introgression influences survival of adults and
subadults in a small, inbred felid population
SO JOURNAL OF ANIMAL ECOLOGY
LA English
DT Article
DE admixture; AIC; Cox proportional hazard; demographic parameter;
heterosis; hybridization; model averaging
ID FLORIDA PANTHER; HYBRID VIGOR; CONSERVATION; HYBRIDIZATION; MANAGEMENT;
EXTINCTION; DISPERSAL; MODELS; METAPOPULATION; RESTORATION
AB 1. Inbreeding and low genetic diversity can cause reductions in individual fitness and increase extinction risk in animal populations. Intentional introgression, achieved by releasing genetically diverse individuals into inbred populations, has been used as a conservation tool to improve demographic performance in endangered populations.
2. By the 1980s, Florida panthers (Puma concolor coryi) had been reduced to a small, inbred population that appeared to be on the brink of extinction. In 1995, female pumas from Texas (P. c. stanleyana) were released in occupied panther range as part of an intentional introgression programme to restore genetic variability and improve demographic performance of panthers.
3. We used 25 years (1981-2006) of continuous radiotelemetry and genetic data to estimate and model subadult and adult panther survival and cause-specific mortality to provide rigorous sex and age class-specific survival estimates and evaluate the effect of the introgression programme on these parameters.
4. Genetic ancestry influenced annual survival of subadults and adults after introgression, as F-1 generation admixed panthers ((s) over cap = 0 98) survived better than pre-introgression type panthers ((s) over cap = 0 77) and other admixed individuals ((s) over cap = 0 82). Furthermore, heterozygosity was higher for admixed panthers relative to pre-introgression type panthers and positively influenced survival.
5. Our results are consistent with hybrid vigour; however, extrinsic factors such as low density of males in some areas of panther range may also have contributed to higher survival of F-1 panthers. Regardless, improved survival of F-1 subadults and adults likely contributed to the numerical increase in panthers following introgression, and our results indicate that intentional admixture, achieved here by releasing individuals from another population, appears to have been successful in improving demographic performance in this highly endangered population.
C1 [Benson, John F.; Onorato, David P.] Florida Fish & Wildlife Conservat Commiss, US Fish & Wildlife Res Inst, Naples, FL 34114 USA.
[Hostetler, Jeffrey A.; Oli, Madan K.] Univ Florida, Dept Wildlife Ecol & Conservat, Gainesville, FL 32611 USA.
[Johnson, Warren E.; Roelke, Melody E.; O'Brien, Stephen J.] NCI, Lab Genom Div, Frederick, MD 21702 USA.
[Roelke, Melody E.] NCI, SAIC Frederick, Frederick, MD 21702 USA.
[Jansen, Deborah] Big Cypress Natl Preserve, Ochopee, FL 34141 USA.
RP Hostetler, JA (reprint author), Smithsonian Conservat Biol Inst, Migratory Bird Ctr, Natl Zool Pk,MRC SS03, Washington, DC 20013 USA.
EM hostetlerj@si.edu
RI Hostetler, Jeffrey/A-3345-2011; Johnson, Warren/D-4149-2016
OI Hostetler, Jeffrey/0000-0003-3669-1758; Johnson,
Warren/0000-0002-5954-186X
FU Florida Panther Research and Management Trust; National Park Service;
University of Florida; United States Fish and Wildlife Service
FX We thank D. Land, M. Cunningham, Roy McBride, M. Lotz, D. Shindle, S.
Schulze, D. Giardina, A. Johnson, S. Bass, L. Oberhofer, M. Alvarado, H.
Fitting and Rocky McBride, Rowdy McBride, C. McBride and others for
assistance with fieldwork. We also thank B. Bolker, D. Valle, J. White,
J. Nichols and G. White for statistical assistance or advice and D.
Land, Roy McBride, B. Bolker, J. Nichols, A. Singh, M. Lotz, M.
Cunningham, T. O'Meara, J. Gore, P. Mahoney and two anonymous reviewers
for reviewing earlier versions of this manuscript. This work was funded
through the Florida Panther Research and Management Trust Fund, National
Park Service, University of Florida, and a grant from the United States
Fish and Wildlife Service.
NR 70
TC 15
Z9 15
U1 1
U2 57
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0021-8790
J9 J ANIM ECOL
JI J. Anim. Ecol.
PD SEP
PY 2011
VL 80
IS 5
BP 958
EP 967
DI 10.1111/j.1365-2656.2011.01809.x
PG 10
WC Ecology; Zoology
SC Environmental Sciences & Ecology; Zoology
GA 798BN
UT WOS:000293176400007
PM 21338353
ER
PT J
AU Pandya, A
Yakel, JL
AF Pandya, Anshul
Yakel, Jerrel L.
TI Allosteric Modulator Desformylflustrabromine Relieves the Inhibition of
alpha 2 beta 2 and alpha 4 beta 2 Nicotinic Acetylcholine Receptors by
beta-Amyloid(1-42) Peptide
SO JOURNAL OF MOLECULAR NEUROSCIENCE
LA English
DT Article
DE Alzheimer's disease (AD); Beta amyloid (A beta(1-42));
Desformylflustrabromine (dFBr); Electrophysiology; Nicotinic
acetylcholine receptors (nAChRs); Positive allosteric modulators (PAMs)
ID ALZHEIMERS-DISEASE; FLUSTRA-FOLIACEA; RAT HIPPOCAMPUS; XENOPUS OOCYTES;
ACH RECEPTORS; BRAIN; NEURONS; SUBTYPE; INTERNEURONS; POTENTIATION
AB Nicotinic acetylcholine receptors (nAChRs) are pentameric transmembrane proteins that belong to the cys-loop ligand-gated ion channel family. These receptors are widely expressed in the brain and implicated in the pathophysiology of many neurological conditions, including Alzheimer's disease (AD), where typical symptoms include the loss of cognitive function and dementia. The presence of extracellular neuritic plaques composed of beta amyloid (A beta(1-42)) peptide is a characteristic feature of AD. Desformylflustrabromine (dFBr) is a positive allosteric modulator (PAM) for alpha 4 beta 2 nAChRs since it increases peak ACh responses without inducing a response on its own. Previously, the effect of dFBr on the alpha 2 beta 2 nAChR subtype was not known. The action of dFBr was tested on alpha 2 beta 2 receptors expressed in Xenopus oocytes. It was found that dFBr is also a PAM for the alpha 2 beta 2 receptor. Next we tested whether dFBr had any effect on the previously known block of both the alpha 4 beta 2 and alpha 2 beta 2 receptors by A beta(1-42). We found that the functional blockade of ACh-induced currents in oocytes expressing alpha 4 beta 2 and alpha 2 beta 2 receptors by A beta(1-42) was prevented by dFBr. We conclude that dFBr is a positive allosteric modulator for both alpha 4 beta 2 and alpha 2 beta 2 subtypes of nAChRs and that it also relieves the blockade of these receptors by A beta(1-42). This study demonstrates that PAMs for the non-alpha 7 nAChRs have the potential to develop into clinically applicable drugs for AD and other disorders.
C1 [Pandya, Anshul; Yakel, Jerrel L.] NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Yakel, JL (reprint author), NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, MD F2-08,POB 12233, Res Triangle Pk, NC 27709 USA.
EM yakel@niehs.nih.gov
FU National Institute of Environmental Health Sciences, NIH
FX We would like to thank Patricia Lamb for the synthesis of mRNA and other
molecular biology work. We extend our appreciation to C. Erxleben and R.
Saha for advice in preparing the manuscript. This research was supported
by the Intramural Research Program of National Institute of
Environmental Health Sciences, NIH.
NR 34
TC 20
Z9 21
U1 2
U2 2
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0895-8696
J9 J MOL NEUROSCI
JI J. Mol. Neurosci.
PD SEP
PY 2011
VL 45
IS 1
BP 42
EP 47
DI 10.1007/s12031-011-9509-3
PG 6
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 798GT
UT WOS:000293191300006
PM 21424792
ER
PT J
AU Houghton, PJ
Lock, R
Carol, H
Morton, CL
Phelps, D
Gorlick, R
Kolb, EA
Keir, ST
Reynolds, CP
Kang, MH
Maris, JM
Wozniak, AW
Gu, YC
Wilson, WR
Smith, MA
AF Houghton, Peter J.
Lock, Richard
Carol, Hernan
Morton, Christopher L.
Phelps, Doris
Gorlick, Richard
Kolb, E. Anders
Keir, Stephen T.
Reynolds, C. Patrick
Kang, Min H.
Maris, John M.
Wozniak, Amy W.
Gu, Yongchuan
Wilson, William R.
Smith, Malcolm A.
TI Initial Testing of the Hypoxia-Activated Prodrug PR-104 by the Pediatric
Preclinical Testing Program
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE developmental therapeutics; preclinical testing; PR-104
ID MARROW HEMATOPOIETIC COMPARTMENT; MODELING PO(2) DISTRIBUTIONS; KETO
REDUCTASE 1C3; SOLID TUMORS; IN-VIVO; CANCER MODELS; SYSTEMIC EXPOSURE;
DRUG DEVELOPMENT; CELL-LINES; XENOGRAFTS
AB Background. PR-104 is rapidly hydrolyzed to PR-104A in vivo, which is activated by reduction to the corresponding 5-hydroxylamine (PR-104H) and amine (PR-104M) to produce DNA interstrand cross-links. PR-104 activation can occur via hypoxia-dependent reductases and also independently of hypoxia by aldo-keto reductase (AKR) 1C3. Procedures. PR-104A was tested against the PPTP in vitropanel(10 nM to 100 mu M), and PR-104 in vivo using a weekly x 6 schedule at its maximum tolerated dose (MTD) of 550 mg/kg. Subsequently PR-104 was tested at 270 and 110 mg/kg. Pharmacokinetics for PR-104 and its metabolites were determined, as were levels of AKR1C3 RNA and protein in xenografts. Results. In vitro, the leukemia models were most sensitive to PR-104A. In vivo, PR-104 induced objective responses at its MTD in 21/34 solid tumor models and maintained complete responses against 7/7 acute lymphoblastic leukemia (ALL) models. At 270 mg/kg and lower dose levels, PR-104 did not induce solid tumor regressions, suggesting a steep dose-response relationship. Pharmacokinetic analysis suggests higher systemic exposures to PR-104A and its metabolites in mice compared to those achievable in patients. Levels of AKR1C3 protein did not correlate with tumor responsiveness. Conclusions. As monotherapy, PR-104 demonstrated a high level of activity against both solid tumor and ALL models at its MTD, but the activity was almost completely lost at half the MTD dose for solid tumors. Pharmacokinetic data at the PR-104 MTD from human trials suggest that PR-104 metabolites may not reach the plasma exposures in children that were associated with high-level preclinical activity. Pediatr Blood Cancer 2011; 57: 443-453. (C) 2010 Wiley-Liss, Inc.
C1 [Houghton, Peter J.] Nationwide Childrens Hosp, Ctr Childhood Canc, Res Inst, Columbus, OH 43205 USA.
[Lock, Richard; Carol, Hernan; Wozniak, Amy W.] Childrens Canc Inst Australia Med Res, Randwick, NSW, Australia.
[Morton, Christopher L.] St Jude Childrens Hosp, Memphis, TN 38105 USA.
[Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA.
[Kolb, E. Anders] Alfred I DuPont Hosp Children, Wilmington, DE USA.
[Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA.
[Reynolds, C. Patrick; Kang, Min H.] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA.
[Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA.
[Gu, Yongchuan; Wilson, William R.] Univ Auckland, Auckland Canc Soc Res Ctr, Auckland 1, New Zealand.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Houghton, PJ (reprint author), Nationwide Childrens Hosp, Ctr Childhood Canc, Res Inst, 700 Childrens Dr, Columbus, OH 43205 USA.
EM peter.houghton@nationwidechildrens.org
RI Houghton, Peter/E-3265-2011; Carol, Hernan/F-5750-2013; Lock,
Richard/G-4253-2013;
OI Carol, Hernan/0000-0002-9443-8032; Reynolds, C.
Patrick/0000-0002-2827-8536
FU National Cancer Institute [NO1-CM-42216, CA21765, CA108786]; Health
Research Council of New Zealand [HRC08/103]
FX Grant sponsor: National Cancer Institute; Grant number: NO1-CM-42216;
Grant number: CA21765; Grant number: CA108786; Grant sponsor: Health
Research Council of New Zealand; Grant number: HRC08/103.
NR 40
TC 13
Z9 14
U1 1
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD SEP
PY 2011
VL 57
IS 3
BP 443
EP 453
DI 10.1002/pbc.22921
PG 11
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 799GD
UT WOS:000293272800015
PM 21744473
ER
PT J
AU Kamdar, KY
Krull, KR
El-Zein, RA
Brouwers, P
Potter, BS
Harris, LL
Holm, S
Dreyer, Z
Scaglia, F
Etzel, CJ
Bondy, M
Okcu, MF
AF Kamdar, Kala Y.
Krull, Kevin R.
El-Zein, Randa A.
Brouwers, Pim
Potter, Brian S.
Harris, Lynnette L.
Holm, Suzanne
Dreyer, ZoAnn
Scaglia, Fernando
Etzel, Carol J.
Bondy, Melissa
Okcu, M. Fatih
TI Folate Pathway Polymorphisms Predict Deficits in Attention and
Processing Speed After Childhood Leukemia Therapy
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE folate; leukemia; neurocognitive; survivor
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; LONG-TERM SURVIVORS; THYMIDYLATE SYNTHASE;
METHYLENETETRAHYDROFOLATE REDUCTASE; INTRAVENOUS METHOTREXATE; PLASMA
HOMOCYSTEINE; CRANIAL RADIATION; CANCER; CHEMOTHERAPY; CHILDREN
AB Background. Neurocognitive impairment occurs in 20-40% of childhood acute lymphoblastic leukemia (ALL) survivors, possibly mediated by folate depletion and homocysteine elevation following methotrexate treatment. We evaluated the relationship between folate pathway polymorphisms and neurocognitive impairment after childhood ALL chemotherapy. Procedure. Seventy-two childhood ALL survivors treated with chemotherapy alone underwent a neurocognitive battery consisting of: Trail Making Tests A (TMTA) and B (TMTB), Grooved Pegboard Test Dominant-Hand and Nondominant-Hand, Digit Span subtest, and Verbal Fluency Test. We performed genotyping for: 10-methylenetetrahydrofolate reductase (MTHFR 677C>T and MTHFR 1298A>C), serine hydroxymethyltransferase (SHMT 1420C>T), methionine synthase (MS 2756 A>G), methionine synthase reductase (MTRR 66A>G), and thymidylate synthase (TSER). Student's two sample t-test and analysis of covariance were used to compare test scores by genotype. Results. General impairment on the neurocognitive battery was related to MTHFR 1298A>C (P = 0.03) and MS 2756A>G (P = 0.05). Specifically, survivors with MTHFR 1298AC/CC genotypes scored, on average, 13 points lower on TMTB than those with MTHFR 1298AA genotype (P = 0.001). The MS 2756AA genotype was associated with a 12.2 point lower mean TMTA score, compared to MS 2756 AG/GG genotypes (P = 0.01). The TSER 2R/3R and 3R/3R genotypes were associated with an 11.4 point lower mean score on TMTB, compared to the TSER 2R/2R genotype (P = 0.03). Survivors with >= 6 folate pathway risk alleles demonstrated a 9.5 point lower mean TMTA score (P = 0.06) and 14.5 point lower TMTB score (P = 0.002) than survivors with <6 risk alleles. Conclusions. Folate pathway polymorphisms are associated with deficits in attention and processing speed after childhood ALL therapy. Pediatr Blood Cancer 2011; 57: 454-460. (C) 2011 Wiley-Liss, Inc.
C1 [Kamdar, Kala Y.; Brouwers, Pim; Harris, Lynnette L.; Holm, Suzanne; Dreyer, ZoAnn; Okcu, M. Fatih] Texas Childrens Canc Ctr, Dept Pediat, Baylor Coll Med, Houston, TX 77030 USA.
[Kamdar, Kala Y.; El-Zein, Randa A.; Bondy, Melissa; Okcu, M. Fatih] Childhood Canc Epidemiol & Prevent Ctr, Houston, TX USA.
[Krull, Kevin R.] St Jude Childrens Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA.
[El-Zein, Randa A.; Etzel, Carol J.; Bondy, Melissa] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Brouwers, Pim] NIMH, Div AIDS Res, Rockville, MD 20857 USA.
[Potter, Brian S.] Ohio State Univ, Dept Pediat, Columbus, OH 43210 USA.
[Scaglia, Fernando] Texas Childrens Hosp, Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
RP Kamdar, KY (reprint author), Texas Childrens Canc Ctr, Dept Pediat, Baylor Coll Med, 1102 Bates St,Suite 1220, Houston, TX 77030 USA.
EM kykamdar@txccc.org
FU NCI [R25T CA57730]
FX Grant sponsor: M.D. Anderson Education Program in Cancer Prevention (NCI
Training, PI: Robert M. Chamberlain); Grant number: R25T CA57730.
NR 43
TC 19
Z9 20
U1 3
U2 7
PU WILEY PERIODICALS, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD SEP
PY 2011
VL 57
IS 3
BP 454
EP 460
DI 10.1002/pbc.23162
PG 7
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 799GD
UT WOS:000293272800016
PM 21618410
ER
PT J
AU Jagoda, EM
Lang, LX
Mccullough, K
Contoreggi, C
Kim, BM
Ma, Y
Rice, KC
Szajek, LP
Eckelman, WC
Kiesewetter, DO
AF Jagoda, Elaine M.
Lang, Lixin
Mccullough, Karen
Contoreggi, Carlo
Kim, B. Moon
Ma, Ying
Rice, Kenner C.
Szajek, Lawrence P.
Eckelman, William C.
Kiesewetter, Dale O.
TI [Br-76]BMK-152, a Nonpeptide Analogue, With High Affinity and Low
Nonspecific Binding for the Corticotropin-Releasing Factor Type 1
Receptor
SO SYNAPSE
LA English
DT Article
DE corticotropin-releasing factor type 1 receptors; CRF1 receptor; Br-76
BMK; PET
ID CENTRAL-NERVOUS-SYSTEM; FACTOR CRF RECEPTORS; ANTAGONIST ANTALARMIN;
AUTORADIOGRAPHIC LOCALIZATION; P-GLYCOPROTEIN; PRIMATE BRAIN; I
RECEPTOR; RAT-BRAIN; G-PROTEIN; HORMONE
AB Corticotropin-releasing factor (CRF), a neuropeptide, regulates endocrine and autonomic responses to stress through G-protein coupled receptors, CRF1 or CRF2. A PET ligand able to monitor changes in CRF1 receptor occupancy in vivo would aid in understanding the pathophysiology of stress-related diseases as well as in the clinical development of nonpeptide antagonists with therapeutic value. We have radiolabeled the CRF1 receptor ligand, [8-(4-bromo-2,6-dimethoxyphenyl)-2,7-dimethylpyrazolo[1,5-alpha][1,3,5]triazin-4-yl]-N,N-bis-(2-methoxyethyl)amine (BMK-152) (ClogP = 2.6), at both the 3 and 4 position with [Br-76]. Using in vitro autoradiography saturation studies the 4-[Br-76]BMK-152 exhibited high affinity binding to both rat (K-d = 0.23 +/- 0.07 nM; n = 3) and monkey frontal cortex (K-d = 0.31 +/- 0.08 nM; n = 3) consistent with CRF1 receptor regional distribution whereas with the 3-[Br-76]BMK-152, the K(d)s could not be determined due to high nonspecific binding. In vitro autoradiography competition studies using [I-125]Tyr(0)-o-CRF confirmed that 3-Br-BMK-152 (K-i = 24.4 +/- 4.9 nM; n = 3) had lower affinity (70-fold) than 4-Br-BMK-152 (K-i = 0.35 +/- 0.07 nM; n 5 3) in monkey frontal cortex and similiar studies using [I-125] Sauvagine confirmed CRF1 receptor selectivity. In vivo studies with P-glycoprotein (PGP) knockout mice ( KO) and their wild-type littermates (WT) showed that the brain uptake of 3-[Br-76]BMK/4-[Br-76]BMK was increased less than twofold in KO versus WT indicating that 3-[Br-76]BMK-152/4-[Br-76]BMK was not a Pgp substrate. Rat brain uptakes of 4-[Br-76]BMK-152 from ex vivo autoradiography studies showed regional localization consistent with known published CRF1 receptor distribution and potential as a PET ligand for in vivo imaging of CRF1 receptors. Synapse 65:910-918, 2011. Published 2011 Wiley-Liss, Inc.
C1 [Jagoda, Elaine M.; Lang, Lixin; Ma, Ying; Kiesewetter, Dale O.] NIBIB, PET Radiochem Grp, NIH, Bethesda, MD USA.
[Mccullough, Karen; Contoreggi, Carlo] NIDA, IRP, NIH, Baltimore, MD USA.
[Kim, B. Moon] Seoul Natl Univ, Coll Nat Sci, Dept Chem, Seoul 151747, South Korea.
[Rice, Kenner C.] NIDDK, LMC, NIH, Bethesda, MD USA.
[Szajek, Lawrence P.] NIH, PET Dept CC, Bethesda, MD 20892 USA.
[Eckelman, William C.] Mol Tracer LLC, Bethesda, MD USA.
RP Jagoda, EM (reprint author), NCI, Mol Imaging Program, 10 Ctr Dr MSC1088,BLG 10-RM B3B69, Bethesda, MD 20892 USA.
EM ejagoda@mail.nih.gov
FU Intramural NIH HHS [Z01 EB000001-03]
NR 50
TC 3
Z9 3
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0887-4476
J9 SYNAPSE
JI Synapse
PD SEP
PY 2011
VL 65
IS 9
BP 910
EP 918
DI 10.1002/syn.20919
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 799GU
UT WOS:000293275200007
PM 21308801
ER
PT J
AU Thanos, PK
Bermeo, C
Wang, GJ
Volkow, ND
AF Thanos, Panayotis K.
Bermeo, Carlos
Wang, Gene-Jack
Volkow, Nora D.
TI D-Cycloserine Facilitates Extinction of Cocaine Self-Administration in
Rats
SO SYNAPSE
LA English
DT Article
DE learning; glutamate; withdrawal; abstinence; drug abuse; NMDA;
addiction; substance abuse
ID CONDITIONED PLACE PREFERENCE; FEAR EXTINCTION; NUCLEUS-ACCUMBENS;
RECEPTORS; REINSTATEMENT; PSYCHOTHERAPY; POTENTIATION; ADDICTION;
BEHAVIOR; SEEKING
AB Previous research has indicated that D-cycloserine [DCS; a N-methyl-D-aspartate (NMDA) partial agonist] facilitates the extinction of conditioned fear as well as the extinction of cocaine conditioned place preference. Sprague Dawley rats were first trained to self-administer cocaine and then we compared their extinction behavior (lever pressing) following treatment with vehicle; 15 mg/kg DCS; or 30 mg/kg DCS. We showed that 30 mg/kg DCS, but not 15 mg/kg significantly accelerated extinction of cocaine self-administration behavior when compared with saline by almost half (4 days vs. 9 days). At 2 weeks when all animals had extinguished, there were no longer differences between the groups. The present findings support of the potential of NMDA partial agonists as prospectively valuable in facilitating the extinction of cocaine-seeking behavior. More specifically, we demonstrate that 30 mg/kg DCS was effective at significantly accelerating the extinction of cocaine self-administration behavior in rats. These results provide further support for the potential of DCS as a treatment strategy for addiction. Synapse 65:938-944, 2011. (C) 2011 Wiley-Liss, Inc.
C1 [Thanos, Panayotis K.; Volkow, Nora D.] NIAAA, Neuroimaging Lab, Intramural Program, NIH, Bethesda, MD USA.
[Thanos, Panayotis K.; Bermeo, Carlos; Wang, Gene-Jack] Brookhaven Natl Lab, Dept Med, Behav Pharmacol & Neuroimaging Lab, Upton, NY 11973 USA.
RP Thanos, PK (reprint author), NIAAA, Neuroimaging Lab, Intramural Program, NIH, Bethesda, MD USA.
EM thanos@bnl.gov9Z
FU NIAAA at the National Institute of Health (NIH); NIDA
FX Contract grant sponsor: The Intramural Research Program of NIAAA at the
National Institute of Health (NIH); Contract grant sponsor: The NIDA
summer research program to C.B.
NR 33
TC 21
Z9 22
U1 2
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0887-4476
J9 SYNAPSE
JI Synapse
PD SEP
PY 2011
VL 65
IS 9
BP 938
EP 944
DI 10.1002/syn.20922
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 799GU
UT WOS:000293275200010
PM 21360592
ER
PT J
AU Kerridge, BT
Saha, TD
Smith, S
Chou, PS
Pickering, RP
Huang, B
Ruan, JW
Pulay, AJ
AF Kerridge, Bradley T.
Saha, Tulshi D.
Smith, Sharon
Chou, Patricia S.
Pickering, Roger P.
Huang, Boji
Ruan, June W.
Pulay, Attila J.
TI Dimensionality of hallucinogen and inhalant/solvent abuse and dependence
criteria: Implications for the diagnostic and statistical manual of
mental disorders-Fifth edition
SO ADDICTIVE BEHAVIORS
LA English
DT Article
DE Hallucinogen use disorder; Inhalant/solvent use disorder; DSM-V; Item
response theory; Dimensionality
ID ITEM RESPONSE THEORY; NATIONAL EPIDEMIOLOGIC SURVEY; ALCOHOL-USE
DISORDERS; DSM-IV CRITERIA; CANNABIS; CONSUMPTION; ADOLESCENTS;
PSYCHOPATHY; COMMUNITY; CONTINUUM
AB Background: Prior research has demonstrated the dimensionality of Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) alcohol, nicotine, cannabis, cocaine and amphetamine abuse and dependence criteria. The purpose of this study was to examine the dimensionality of hallucinogen and inhalant/solvent abuse and dependence criteria. In addition, we assessed the impact of elimination of the legal problems abuse criterion on the information value of the aggregate abuse and dependence criteria, another proposed change for DSM-IV currently lacking empirical justification.
Methods: Factor analyses and item response theory (IRT) analyses were used to explore the unidimisionality and psychometric properties of hallucinogen and inhalant/solvent abuse and dependence criteria using a large representative sample of the United States (U.S.) general population.
Results: Hallucinogen and inhalant/solvent abuse and dependence criteria formed unidimensional latent traits. For both substances, IRT models without the legal problems abuse criterion demonstrated better fit than the corresponding model with the legal problem abuse criterion. Further, there were no differences in the information value of the IRT models with and without the legal problems abuse criterion, supporting the elimination of that criterion. No bias in the new diagnoses was observed by sex, age and race-ethnicity.
Conclusion: Consistent with findings for alcohol, nicotine, cannabis, cocaine and amphetamine abuse and dependence criteria, hallucinogen and inhalant/solvent criteria reflect underlying dimensions of severity. The legal problems criterion associated with each of these substance use disorders can be eliminated with no loss in informational value and an advantage of parsimony. Taken together, these findings support the changes to substance use disorder diagnoses recommended by the DSM-V Substance and Related Disorders Workgroup, that is, combining DSM-IV abuse and dependence criteria and eliminating the legal problems abuse criterion. Published by Elsevier Ltd.
C1 [Saha, Tulshi D.; Smith, Sharon; Chou, Patricia S.; Pickering, Roger P.; Huang, Boji; Ruan, June W.; Pulay, Attila J.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA.
[Kerridge, Bradley T.] Univ Maryland, Dept Epidemiol & Biostat, Sch Publ Hlth, College Pk, MD 20740 USA.
RP Saha, TD (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, 5635 Fishers Lane,Room 3083, Bethesda, MD 20892 USA.
EM sahatd@mail.nih.gov
OI Kerridge, Bradley/0000-0003-0459-9439
FU National Institute on Alcohol Abuse and Alcoholism (NIAAA); National
Institute on Drug Abuse (NIDA); National Institutes of Health (NIH),
NIAAA; NIH/NIDA [5F31DA025377]
FX The National Institute on Alcohol Abuse and Alcoholism (NIAAA) funded
the National Epidemiologic Survey on Alcohol and Related Conditions
(NESARC) with supplemental funding from the National Institute on Drug
Abuse (NIDA). Funding was also from the International Program of the
National Institutes of Health (NIH), NIAAA. Support for Mr. Kerridge,
NIH/NIDA Fellowship 5F31DA025377 is acknowledged.
NR 34
TC 11
Z9 11
U1 3
U2 3
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 2011
VL 36
IS 9
BP 912
EP 918
DI 10.1016/j.addbeh.2011.04.006
PG 7
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA 793GO
UT WOS:000292808600003
PM 21621334
ER
PT J
AU Soria, JA
Arroyo, DS
Gaviglio, EA
Rodriguez-Galan, MC
Wang, JM
Iribarren, P
AF Soria, Javier A.
Arroyo, Daniela S.
Gaviglio, Emilia A.
Rodriguez-Galan, Maria C.
Wang, Ji Ming
Iribarren, Pablo
TI Interleukin 4 induces the apoptosis of mouse microglial cells by a
caspase-dependent mechanism
SO NEUROBIOLOGY OF DISEASE
LA English
DT Article
DE Microglia; Interleukin 4; Apoptosis; Caspases; Neuroinflammation
ID FORMYL PEPTIDE RECEPTOR-2; ACTIVATED MICROGLIA; ALTERNATIVE ACTIVATION;
REACTIVE MICROGLIOSIS; POPULATION-CONTROL; DENDRITIC CELLS; IN-VIVO;
IL-4; EXPRESSION; PROTEIN
AB Microglial cells are resident macrophages in the central nervous system (CNS) and become activated in many pathological conditions. Activation of microglial cells results in reactive microgliosis, manifested by an increase in cell number in the affected CNS regions. The control of microgliosis may be important to prevent pathological damage to the brain. The type 2 cytokine IL-4 has been reported to be protective in brain inflammation. However, its effect on microglial cell survival was not well understood. In this study, we report a dual effect of IL-4 on the survival of mouse microglial cells. In a 6 h short term culture. IL-4 reduced the death of microglial cells induced by staurosporine. In contrast, in long term treatment (more than 48 h), IL-4 increased the apoptotic death of both primary mouse microglial cells and a microglial cell line N9. Mechanistic studies revealed that, in microglial cells, IL-4 increased the levels of cleaved caspase 3 and PARP, which is down-stream of activated caspase 3. In addition, IL-4 down regulated the autophagy and the antiapoptotic protein Bcl-xL in microglial cells. On the other hand, the pre-incubation of microglial cells with IL-4 for 24 h, attenuated the cell death induced by the neurotoxic peptide amyloid beta 1-42 (A beta 42). Our observations demonstrate a novel function of IL-4 in regulating the survival of microglial cells, which may have important significance in reduction of undesired inflammatory responses in the CNS. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Soria, Javier A.; Arroyo, Daniela S.; Gaviglio, Emilia A.; Rodriguez-Galan, Maria C.; Iribarren, Pablo] Univ Nacl Cordoba, Fac Ciencias Quim, Dept Bioquim Clin, Ctr Invest Bioquim Clin & Inmunol CIBICI CONICET, RA-5000 Cordoba, Argentina.
[Wang, Ji Ming] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.
RP Iribarren, P (reprint author), Univ Nacl Cordoba, Fac Ciencias Quim, Dept Bioquim Clin, Ctr Invest Bioquim Clin & Inmunol CIBICI CONICET, Ciudad Univ,X5000HUA, RA-5000 Cordoba, Argentina.
EM piribarr@fcq.unc.edu.ar
FU Fogarty International Center, NIH, USA [1R01TW007621-01A2]; CONICET;
SECyT-UNC, Argentina
FX This work was supported by grant number 1R01TW007621-01A2 from Fogarty
International Center, NIH, USA, CONICET and SECyT-UNC, Argentina. Its
contents are solely the responsibility of the authors and do not
necessarily represent the official views of the Fogarty International
Center (FIC), NIH, USA.
NR 55
TC 15
Z9 15
U1 0
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0969-9961
J9 NEUROBIOL DIS
JI Neurobiol. Dis.
PD SEP
PY 2011
VL 43
IS 3
BP 616
EP 624
DI 10.1016/j.nbd.2011.05.010
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 796GX
UT WOS:000293040900010
PM 21624466
ER
PT J
AU Coddou, C
Yan, ZH
Obsil, T
Huidobro-Toro, JP
Stojilkovic, SS
AF Coddou, Claudio
Yan, Zonghe
Obsil, Tomas
Pablo Huidobro-Toro, J.
Stojilkovic, Stanko S.
TI Activation and Regulation of Purinergic P2X Receptor Channels
SO PHARMACOLOGICAL REVIEWS
LA English
DT Review
ID GATED ION CHANNELS; ROOT GANGLION NEURONS; PROTEIN-KINASE-C;
AMINO-ACID-RESIDUES; PIG URINARY-BLADDER; MESSENGER-RNA EXPRESSION;
ANTERIOR-PITUITARY-CELLS; ATP-INDUCED CURRENTS; NEGATIVELY CHARGED
RESIDUES; FIRST TRANSMEMBRANE DOMAIN
AB Mammalian ATP-gated nonselective cation channels (P2XRs) can be composed of seven possible subunits, denoted P2X1 to P2X7. Each subunit contains a large ectodomain, two transmembrane domains, and intracellular N and C termini. Functional P2XRs are organized as homomeric and heteromeric trimers. This review focuses on the binding sites involved in the activation (orthosteric) and regulation (allosteric) of P2XRs. The ectodomains contain three ATP binding sites, presumably located between neighboring subunits and formed by highly conserved residues. The detection and coordination of three ATP phosphate residues by positively charged amino acids are likely to play a dominant role in determining agonist potency, whereas an AsnPheArg motif may contribute to binding by coordinating the adenine ring. Nonconserved ectodomain histidines provide the binding sites for trace metals, divalent cations, and protons. The transmembrane domains account not only for the formation of the channel pore but also for the binding of ivermectin (a specific P2X4R allosteric regulator) and alcohols. The N- and C-domains provide the structures that determine the kinetics of receptor desensitization and/or pore dilation and are critical for the regulation of receptor functions by intracellular messengers, kinases, reactive oxygen species and mercury. The recent publication of the crystal structure of the zebrafish P2X4.1R in a closed state provides a major advance in the understanding of this family of receptor channels. We will discuss data obtained from numerous site-directed mutagenesis experiments accumulated during the last 15 years with reference to the crystal structure, allowing a structural interpretation of the molecular basis of orthosteric and allosteric ligand actions.
C1 [Coddou, Claudio; Yan, Zonghe; Stojilkovic, Stanko S.] NICHHD, Sect Cellular Signaling, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
[Obsil, Tomas] Charles Univ Prague, Dept Phys & Macromol Chem, Fac Sci, Prague, Czech Republic.
[Pablo Huidobro-Toro, J.] Pontificia Univ Catolica Chile, Ctr Envejecimiento & Regenerac, Ctr Regulac Celular & Patol Prof JV Luco,Fac Cien, Inst Milenio Biol Fundamental & Aplicada,Dept Fis, Santiago, Chile.
RP Stojilkovic, SS (reprint author), NICHD, Sect Cellular Signaling, PDN, NIH, Bldg 49,Room 6A36, Bethesda, MD 20892 USA.
EM stojilks@mail.nih.gov
RI Obsil, Tomas/B-7142-2012
OI Obsil, Tomas/0000-0003-4602-1272
FU National Institutes of Health National Institute of Child Health and
Human Development; Internal Grant Agency of the Academy of Sciences;
Fondo de Financiamiento de Centros de Excelencia en Investigacion
[13980001]; Instituto Milenio de Biologia Fundamental y Aplicada; PFB
[12/2007]
FX This research was funded in part by the Intramural Research Program of
the National Institutes of Health National Institute of Child Health and
Human Development (to C. C., Z.Y., S. S. S.); the Internal Grant Agency
of the Academy of Sciences (to T.O.); the Fondo de Financiamiento de
Centros de Excelencia en Investigacion [Grant 13980001], and the
Instituto Milenio de Biologia Fundamental y Aplicada and PFB 12/2007 (to
J.P.H.-T.).
NR 548
TC 198
Z9 201
U1 18
U2 58
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0031-6997
J9 PHARMACOL REV
JI Pharmacol. Rev.
PD SEP
PY 2011
VL 63
IS 3
BP 641
EP 683
DI 10.1124/pr.110.003129
PG 43
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 793ZK
UT WOS:000292862800005
PM 21737531
ER
PT J
AU Stutzmann, GE
Mattson, MP
AF Stutzmann, Grace E.
Mattson, Mark P.
TI Endoplasmic Reticulum Ca2+ Handling in Excitable Cells in Health and
Disease
SO PHARMACOLOGICAL REVIEWS
LA English
DT Review
ID AMYLOID-BETA-PEPTIDE; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR;
CALCIUM-RELEASE CHANNEL; CULTURED HIPPOCAMPAL-NEURONS; CARDIAC RYANODINE
RECEPTOR; LONG-TERM POTENTIATION; KNOCK-IN MICE; POLYMORPHIC
VENTRICULAR-TACHYCARDIA; AMYOTROPHIC-LATERAL-SCLEROSIS;
ISCHEMIA-REPERFUSION INJURY
AB The endoplasmic reticulum (ER) is a morphologically and functionally diverse organelle capable of integrating multiple extracellular and internal signals and generating adaptive cellular responses. It plays fundamental roles in protein synthesis and folding and in cellular responses to metabolic and proteotoxic stress. In addition, the ER stores and releases Ca2+ in sophisticated scenarios that regulate a range of processes in excitable cells throughout the body, including muscle contraction and relaxation, endocrine regulation of metabolism, learning and memory, and cell death. One or more Ca2+ ATPases and two types of ER membrane Ca2+ channels (inositol trisphosphate and ryanodine receptors) are the major proteins involved in ER Ca2+ uptake and release, respectively. There are also direct and indirect interactions of ER Ca2+ stores with plasma membrane and mitochondrial Ca2+-regulating systems. Pharmacological agents that selectively modify ER Ca2+ release or uptake have enabled studies that revealed many different physiological roles for ER Ca2+ signaling. Several inherited diseases are caused by mutations in ER Ca2+-regulating proteins, and perturbed ER Ca2+ homeostasis is implicated in a range of acquired disorders. Preclinical investigations suggest a therapeutic potential for use of agents that target ER Ca2+ handling systems of excitable cells in disorders ranging from cardiac arrhythmias and skeletal muscle myopathies to Alzheimer disease.
C1 [Stutzmann, Grace E.] Rosalind Franklin Univ, Chicago Med Sch, Dept Neurosci, N Chicago, IL 60064 USA.
[Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
RP Stutzmann, GE (reprint author), Rosalind Franklin Univ, Chicago Med Sch, Dept Neurosci, 3333 Green Bay Rd, N Chicago, IL 60064 USA.
EM grace.stutzmann@rosalindfranklin.edu
RI Mattson, Mark/F-6038-2012
FU National Institutes of Health National Institute on Aging [AG030205]
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health National Institute on Aging (to M.
M.); and by the National Institutes of Health National Institute on
Aging [Grant AG030205] (to G. E. S.). We thank K. C. Alexander for
assistance in the preparation of figures and Corinne Schneider for
editorial assistance.
NR 338
TC 94
Z9 100
U1 2
U2 22
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0031-6997
J9 PHARMACOL REV
JI Pharmacol. Rev.
PD SEP
PY 2011
VL 63
IS 3
BP 700
EP 727
DI 10.1124/pr.110.003814
PG 28
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 793ZK
UT WOS:000292862800007
PM 21737534
ER
PT J
AU Hutchinson, MR
Shavit, Y
Grace, PM
Rice, KC
Maier, SF
Watkins, LR
AF Hutchinson, Mark R.
Shavit, Yehuda
Grace, Peter M.
Rice, Kenner C.
Maier, Steven F.
Watkins, Linda R.
TI Exploring the Neuroimmunopharmacology of Opioids: An Integrative Review
of Mechanisms of Central Immune Signaling and Their Implications for
Opioid Analgesia
SO PHARMACOLOGICAL REVIEWS
LA English
DT Review
ID ROSTRAL VENTROMEDIAL MEDULLA; ACTIVATED PROTEIN-KINASE; TOLL-LIKE
RECEPTOR; MORPHINE ANTINOCICEPTIVE TOLERANCE; PERIPHERAL-NERVE INJURY;
BLOOD-BRAIN-BARRIER; MONOCYTE CHEMOATTRACTANT PROTEIN-1; DORSAL-ROOT
GANGLIA; FIBRILLARY ACIDIC PROTEIN; MOUSE MICROGLIAL CELLS
AB Vastly stimulated by the discovery of opioid receptors in the early 1970s, preclinical and clinical research was directed at the study of stereo-selective neuronal actions of opioids, especially those played in their crucial analgesic role. However, during the past decade, a new appreciation of the non-neuronal actions of opioids has emerged from preclinical research, with specific appreciation for the nonclassic and nonstereoselective sites of action. Opioid activity at Toll-like receptors, newly recognized innate immune pattern recognition receptors, adds substantially to this unfolding story. It is now apparent from molecular and rodent data that these newly identified signaling events significantly modify the pharmacodynamics of opioids by eliciting proinflammatory reactivity from glia, the immunocompetent cells of the central nervous system. These central immune signaling events, including the release of cytokines and chemokines and the associated disruption of glutamate homeostasis, cause elevated neuronal excitability, which subsequently decreases opioid analgesic efficacy and leads to heightened pain states. This review will examine the current preclinical literature of opioid-induced central immune signaling mediated by classic and nonclassic opioid receptors. A unification of the preclinical pharmacology, neuroscience, and immunology of opioids now provides new insights into common mechanisms of chronic pain, naive tolerance, analgesic tolerance, opioid-induced hyperalgesia, and allodynia. Novel pharmacological targets for future drug development are discussed in the hope that disease-modifying chronic pain treatments arising from the appreciation of opioid-induced central immune signaling may become practical.
C1 [Hutchinson, Mark R.; Grace, Peter M.] Univ Adelaide, Sch Med Sci, Discipline Physiol, S Australia, SA 5005, Australia.
[Hutchinson, Mark R.] Univ Adelaide, Sch Med Sci, Discipline Physiol, S Australia, SA 5005, Australia.
[Hutchinson, Mark R.; Maier, Steven F.; Watkins, Linda R.] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA.
[Shavit, Yehuda] Hebrew Univ Jerusalem, Dept Psychol, IL-91905 Jerusalem, Israel.
[Rice, Kenner C.] NIDA, Chem Biol Res Branch, Rockville, MD 90034 USA.
[Rice, Kenner C.] NIAAA, Rockville, MD 20852 USA.
RP Hutchinson, MR (reprint author), Univ Adelaide, Sch Med Sci, Discipline Physiol, S Australia, SA 5005, Australia.
EM mark.hutchinson@adelaide.edu.au
RI Grace, Peter/I-5507-2013; Shavit, Yehuda/A-1219-2010; Hutchinson,
Mark/G-4147-2014
OI Grace, Peter/0000-0002-8999-1220; Hutchinson, Mark/0000-0003-2154-5950
FU National Institutes of Health National Institute on Drug Abuse; National
Institutes of Health National Institute on Alcohol Abuse and Alcoholism
[K05-DA024044]; National Health and Medical Research Council [ID
465423]; Australian Research Council [DP110100297]; Faculty of Health
Sciences Divisional Scholarship; Israel Science Foundation [512/08];
Leon and Clara Sznajderman Chair of Psychology
FX This work was supported in part by the Intramural Research Programs of
the National Institutes of Health National Institute on Drug Abuse and
the National Institutes of Health National Institute on Alcohol Abuse
and Alcoholism (to K. C. R.); the National Institutes of Health National
Institute on Alcohol Abuse and Alcoholism [Grant K05-DA024044] (to L. R.
W.); the National Health and Medical Research Council CJ Martin
Fellowship [ID 465423, 2010] (to M. R. H.); the Australian Research
Council Australian Research Fellowship [DP110100297, 2011] (to M. R.
H.); a Faculty of Health Sciences Divisional Scholarship (to P. M. G.);
the Israel Science Foundation [Grant 512/08] (to Y.S.); and the Leon and
Clara Sznajderman Chair of Psychology (to Y.S.). Thanks to Tavik
Morgenstern for assistance inpreparing the figures.
NR 488
TC 123
Z9 129
U1 5
U2 32
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0031-6997
J9 PHARMACOL REV
JI Pharmacol. Rev.
PD SEP
PY 2011
VL 63
IS 3
BP 772
EP 810
DI 10.1124/pr.110.004135
PG 39
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 793ZK
UT WOS:000292862800010
PM 21752874
ER
PT J
AU Feng, Y
Gong, R
Dimitrov, DS
AF Feng, Yang
Gong, Rui
Dimitrov, Dimiter S.
TI Design, expression and characterization of a soluble single-chain
functional human neonatal Fc receptor
SO PROTEIN EXPRESSION AND PURIFICATION
LA English
DT Article
DE Neonatal Fc receptor; FcRn; IgG half-life
ID I-RELATED RECEPTOR; SERUM HALF-LIFE; HUMAN IGG1; EPITHELIAL-CELLS;
IMMUNOGLOBULIN-G; AFFINITY; BINDING; ANTIBODY; STOICHIOMETRY; SITE
AB The neonatal Fc receptor (FcRn) is responsible for transporting maternal IgGs to fetus/newborns and maintaining the homeostasis of IgGs in adults. FcRn resembles class I major histocompatibility complex in structure, and is composed of a transmembrane heavy chain and an invariant beta 2 microglobulin. Changes in the affinity of IgGs to FcRn lead to changes in the half-life of engineered IgGs and Fc fusion proteins. Longer half-life of therapeutic antibodies means lower dose and longer interval between administering. For some diagnostic agents including imaging or radio-labeled agents a shorter half life in circulation results in lower non-specific binding and decreased side effects. Therefore, studying the interaction of FcRn and therapeutic antibodies has direct clinical implications. A reliable method to prepare soluble and functional FcRn protein is essential for such studies. In this study, we describe a new method to express in mammalian cells soluble human FcRn (sFcRn) as a single-chain soluble fusion protein. The highly hydrophilic beta 2 microglobulin was joined with the hydrophobic heavy chain via a 15 amino acid linker. The single-chain fusion protein format not only improved the expression level of the heavy chain but also simplified the purification process. The sFcRn maintained its pH-dependent binding to IgG. This method typically yielded similar to 1 mg/100 ml culture without optimization, and is easy to scale up for production of large quantities. Published by Elsevier Inc.
C1 [Feng, Yang; Gong, Rui; Dimitrov, Dimiter S.] NCI, Prot Interact Grp, CCR Nanobiol Program, NIH, Frederick, MD 21702 USA.
RP Feng, Y (reprint author), NCI, Prot Interact Grp, CCR Nanobiol Program, NIH, Bldg 469,Rm 140, Frederick, MD 21702 USA.
EM fengya@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX We thank members of our groups for helpful discussions. 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 by the Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research.
NR 23
TC 15
Z9 15
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1046-5928
J9 PROTEIN EXPRES PURIF
JI Protein Expr. Purif.
PD SEP
PY 2011
VL 79
IS 1
BP 66
EP 71
DI 10.1016/j.pep.2011.03.012
PG 6
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biotechnology & Applied Microbiology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
GA 795SM
UT WOS:000292996100009
PM 21453773
ER
PT J
AU Yang, MH
Sun, S
Kostov, Y
Rasooly, A
AF Yang, Minghui
Sun, Steven
Kostov, Yordan
Rasooly, Avraham
TI An automated point-of-care system for immunodetection of staphylococcal
enterotoxin B
SO ANALYTICAL BIOCHEMISTRY
LA English
DT Article
DE Point of care; ELISA; Lab-on-a-chip; Open platform; CCD;
Microfabrication; Staphylococcal enterotoxins; Food safety
ID ENHANCED CHEMILUMINESCENCE IMMUNOASSAY; ON-A-CHIP; ATOPIC-DERMATITIS;
RHEUMATOID-ARTHRITIS; CARBON NANOTUBES; SUPERANTIGENS; ANTIBODIES; FOOD;
SEB; IMMUNOSENSOR
AB An automated point-of-care (POC) immunodetection system for immunological detection of staphylococcal enterotoxin B (SEB) was designed, fabricated, and tested. The system combines several elements: (i) enzyme-linked immunosorbent assay-lab-on-a-chip (ELISA-LOC) with fluidics, (ii) a charge-coupled device (CCD) camera detector, (iii) pumps and valves for fluid delivery to the ELISA-LOC, (iv) a computer interface board, and (v) a computer for controlling the fluidics, logging, and data analysis of the CCD data. The ELISA-LOC integrates a simple microfluidic system into a miniature 96-well sample plate, allowing the user to carry out immunological assays without a laboratory. The analyte is measured in a sandwich ELISA assay format combined with a sensitive electrochemiluminescence (ECL) detection method. Using the POC system, SEB, a major foodborne toxin, was detected at concentrations as low as 0.1 ng/ml. This is similar to the reported sensitivity of conventional ELISA. The open platform with simple modular fluid delivery automation design described here is interchangeable between detection systems, and because of its versatility it can also be used to automate many other LOC systems, simplifying LOC development. This new POC system is useful for carrying out various immunological and other complex medical assays without a laboratory and can easily be adapted for high-throughput biological screening in remote and resource-poor areas. Published by Elsevier Inc.
C1 [Yang, Minghui; Sun, Steven; Kostov, Yordan] Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA.
[Yang, Minghui] Univ Jinan, Sch Chem & Chem Engn, Jinan 250022, Peoples R China.
[Sun, Steven; Rasooly, Avraham] Food & Drug Adm, Off Sci & Engn, Div Biol, Silver Spring, MD 20993 USA.
[Rasooly, Avraham] NCI, Bethesda, MD 20892 USA.
RP Rasooly, A (reprint author), NCI, 6130 Executive Blvd, Rockville, MD 20852 USA.
EM rasoolya@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 51
TC 25
Z9 25
U1 1
U2 35
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0003-2697
J9 ANAL BIOCHEM
JI Anal. Biochem.
PD SEP 1
PY 2011
VL 416
IS 1
BP 74
EP 81
DI 10.1016/j.ab.2011.05.014
PG 8
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 790XG
UT WOS:000292623500010
PM 21640067
ER
PT J
AU Adhikari, S
Karmahapatra, SK
Elias, H
Dhopeshwarkar, P
Williams, RS
Byers, S
Uren, A
Roy, R
AF Adhikari, Sanjay
Karmahapatra, Soumendra K.
Elias, Hadi
Dhopeshwarkar, Priyanka
Williams, R. Scott
Byers, Stephen
Uren, Aykut
Roy, Rabindra
TI Development of a novel assay for human tyrosyl DNA phosphodiesterase 2
SO ANALYTICAL BIOCHEMISTRY
LA English
DT Article
DE DNA repair; Enzyme assay; Kinetics; TDP2; High-throughput screening
ID TOPOISOMERASE-II; ANTITUMOR DRUGS; DAMAGE; REPAIR; CELLS; NUCLEI; ENZYME
AB Tyrosyl DNA phosphodiesterase 2 (TDP2), a newly discovered enzyme that cleaves 5'-phosphotyrosyl bonds, is a potential target for chemotherapy. TDP2 possesses both 3'- and 5'-tyrosyl-DNA phosphodiesterase activity, which is generally measured in a gel-based assay using 3'- and 5'-phosphotyrosyl linkage at the 3' and 5' ends of an oligonucleotide. To understand the enzymatic mechanism of this novel enzyme, the gel-based assay is useful, but this technique is cumbersome for TDP2 inhibitor screening. For this reason, we have designed a novel assay using p-nitrophenyl-thymidine-5'-phosphate (T5PNP) as a substrate. This assay can be used in continuous colorimetric assays in a 96-well format. We compared the salt and pH effect on product formation with the colorimetric and gel-based assays and showed that they behave similarly. Steady-state kinetic studies showed that the 5' activity of TDP2 is 1000-fold more efficient than T5PNP. Tyrosyl DNA phosphodiesterase 1 (TDP1) and human AP-endonuclease 1 (APE1) could not hydrolyze T5PNP. Sodium orthovanadate, a known inhibitor of TDP2, inhibits product formation from T5PNP by TDP2 (IC(50) = 40 mM). Our results suggest that this novel assay system with this new TDP2 substrate can be used for inhibitor screening in a high-throughput manner. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Adhikari, Sanjay; Karmahapatra, Soumendra K.; Elias, Hadi; Dhopeshwarkar, Priyanka; Byers, Stephen; Uren, Aykut; Roy, Rabindra] Georgetown Univ, Dept Oncol, Lombardi Comprehens Canc Ctr, Med Ctr, Washington, DC 20057 USA.
[Williams, R. Scott] Natl Inst Environm Hlth Sci, Struct Biol Lab, Res Triangle Pk, NC 27709 USA.
RP Adhikari, S (reprint author), Georgetown Univ, Dept Oncol, Lombardi Comprehens Canc Ctr, Med Ctr, Washington, DC 20057 USA.
EM sa354@georgetown.edu
RI Williams, Robert/A-6059-2015
FU American Cancer Society [IRG-92-152-17]; National Institutes of Health
[RO1 CA 92306]
FX This work was supported by American Cancer Society Grant IRG-92-152-17
(American Cancer Society Institutional Research Grant to S.A.) and
National Institutes of Health Grant RO1 CA 92306 (to R.R.). We thank
Elsevier Language Editing Services for editing the manuscript. We also
thank Jordan Woodrick for critically reading the manuscript.
NR 22
TC 12
Z9 12
U1 1
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0003-2697
J9 ANAL BIOCHEM
JI Anal. Biochem.
PD SEP 1
PY 2011
VL 416
IS 1
BP 112
EP 116
DI 10.1016/j.ab.2011.05.008
PG 5
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 790XG
UT WOS:000292623500015
PM 21620793
ER
PT J
AU Altunbas, A
Lee, SJ
Rajasekaran, SA
Schneider, JP
Pochan, DJ
AF Altunbas, Aysegul
Lee, Seung J.
Rajasekaran, Sigrid A.
Schneider, Joel P.
Pochan, Darrin J.
TI Encapsulation of curcumin in self-assembling peptide hydrogels as
injectable drug delivery vehicles
SO BIOMATERIALS
LA English
DT Article
DE Peptide; Self-assembly; Curcumin; Hydrogel
ID CANCER-CELLS; BIOMEDICAL APPLICATIONS; REVERSIBLE HYDROGELS;
CONTROLLED-RELEASE; DESIGNED PEPTIDE; APOPTOSIS; NANOCARRIER; ANTITUMOR;
PROTEINS; MEDICINE
AB Curcumin, a hydrophobic polyphenol, is an extract of turmeric root with antioxidant, anti-inflammatory and anti-tumorigenic properties. Its lack of water solubility and relatively low bioavailability set major limitations for its therapeutic use. In this study, a self-assembling peptide hydrogel is demonstrated to be an effective vehicle for the localized delivery of curcumin over sustained periods of time. The curcumin-hydrogel is prepared in-situ where curcumin encapsulation within the hydrogel network is accomplished concurrently with peptide self-assembly. Physical and in vitro biological studies were used to demonstrate the effectiveness of curcumin-loaded beta-hairpin hydrogels as injectable agents for localized curcumin delivery. Notably, theological characterization of the curcumin-loaded hydrogel before and after shear flow have indicated solid-like properties even at high curcumin payloads. In vitro experiments with a medulloblastoma cell line confirm that the encapsulation of the curcumin within the hydrogel does not have an adverse effect on its bioactivity. Most importantly, the rate of curcumin release and its consequent therapeutic efficacy can be conveniently modulated as a function of the concentration of the MAX8 peptide. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Altunbas, Aysegul; Pochan, Darrin J.] Univ Delaware, Dept Mat Sci & Engn, Newark, DE 19716 USA.
[Altunbas, Aysegul; Pochan, Darrin J.] Univ Delaware, Delaware Biotechnol Inst, Newark, DE 19716 USA.
[Lee, Seung J.; Rajasekaran, Sigrid A.] Alfred I DuPont Hosp Children, Nemours Ctr Childhood Canc Res, Canc Epigenet Lab, Wilmington, DE 19803 USA.
[Schneider, Joel P.] NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA.
RP Pochan, DJ (reprint author), Univ Delaware, Dept Mat Sci & Engn, 201 DuPont Hall, Newark, DE 19716 USA.
EM pochan@udel.edu
RI Osorio Tobon, Juan Felipe/G-6877-2012; Schneider, Joel/N-2610-2014
FU NIH COBRE [P20 RR017716]; American Cancer Society [RSG-09-021-01-CNE];
Nemours Foundation; College of Engineering at the University of Delaware
FX AA and SJL have contributed equally to this work. This work was
supported by the NIH COBRE P20 RR017716, American Cancer Society
Research Grant RSG-09-021-01-CNE and funds from the Nemours Foundation
to Sigrid A. Rajasekaran. We thank C. Ni, F. Kriss and the College of
Engineering at the University of Delaware, for partial funding of W.M.
Keck Electron Microscopy Facility.
NR 68
TC 170
Z9 176
U1 22
U2 217
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0142-9612
J9 BIOMATERIALS
JI Biomaterials
PD SEP
PY 2011
VL 32
IS 25
BP 5906
EP 5914
DI 10.1016/j.biomaterials.2011.04.069
PG 9
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA 792BE
UT WOS:000292714700019
PM 21601921
ER
PT J
AU Furusato, E
Shen, DF
Cao, XG
Furusato, B
Nussenblatt, RB
Rushing, EJ
Chan, CC
AF Furusato, Emiko
Shen, DeFen
Cao, Xiaoguang
Furusato, Bungo
Nussenblatt, Robert B.
Rushing, Elisabeth J.
Chan, Chi-Chao
TI Inflammatory cytokine and chemokine expression in sympathetic
ophthalmia: a pilot study
SO HISTOLOGY AND HISTOPATHOLOGY
LA English
DT Article
DE Chemokines; Cytokines; Macrophages; Sympathetic ophthalmia; Uveitis
ID KOYANAGI-HARADA SYNDROME; T-CELLS; MACROPHAGE ACTIVATION; ALVEOLAR
MACROPHAGES; ELECTRON-MICROSCOPY; LUNG INFLAMMATION; CXC CHEMOKINE;
POLARIZATION; DISEASE; GENE
AB Sympathetic ophthalmia is a bilateral uveitis that develops after penetrating injury to one eye. This study aimed to identify the inflammatory cellular sub-phenotypes and expression of pertinent inflammatory cytokines/chemokines in sympathetic ophthalmia (SO). Dalen-Fuchs nodules (DFN), granulomas, and non-granulomatous foci of inflammation were micro-dissected from 15 cases. RNA was extracted, and quantitative PCR was performed to measure IL-17, IL-18, IL-23, IFN-gamma, CCL19, CXCL11, CCL17, and CCL22 transcripts. Immunohistochemical methods were used to characterize CD3, CD4, CD8, CD20, CD68, and CD163 expression. Non-granulomatous lymphocytes were predominantly CD3-positive and expressed more IFN-gamma than cells within granulomas, consistent with Th1 cells. In contrast, granulomas and DFN contained mainly CD68+, CD163+/- and expressed more IL-17, IL-18, IL-23, CCL19, and CXCL11 than non-granulomatous cells. Our data indicate for the first time that M1 macrophages are the predominant inflammatory cells within granulomas and DFN of SO. We further observed high levels of IL-17 within granulomas and the presence of Th1 and M1 cells.
C1 [Furusato, Emiko; Shen, DeFen; Cao, Xiaoguang; Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Furusato, Emiko; Rushing, Elisabeth J.] NEI, Clin Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Furusato, Bungo; Nussenblatt, Robert B.] Armed Forces Inst Pathol, Washington, DC 20306 USA.
RP Chan, CC (reprint author), NEI, Immunopathol Sect, Immunol Lab, NIH, 10 Ctr Dr,Bldg 10,Rm 10N103, Bethesda, MD 20892 USA.
EM chanc@nei.nih.gov
OI Furusato, Bungo/0000-0003-4614-9882
FU NEI
FX This study was supported by the NEI Intramural Research Program.
NR 41
TC 8
Z9 8
U1 1
U2 1
PU F HERNANDEZ
PI MURCIA
PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN
SN 0213-3911
J9 HISTOL HISTOPATHOL
JI Histol. Histopath.
PD SEP
PY 2011
VL 26
IS 9
BP 1145
EP 1151
PG 7
WC Cell Biology; Pathology
SC Cell Biology; Pathology
GA 791RZ
UT WOS:000292683600005
PM 21751146
ER
PT J
AU Liang, HS
Zhong, YH
Zhou, SB
Li, QQ
AF Liang, Huasheng
Zhong, Yuhua
Zhou, Shaobi
Li, Qingdi Quentin
TI Palmitic Acid-induced Apoptosis in Pancreatic beta-Cells Is Increased by
Liver X Receptor Agonist and Attenuated by Eicosapentaenoate
SO IN VIVO
LA English
DT Article
DE Liver X receptors; palmitic acid; apoptosis; INS-1 cells; SREBP-1;
eicosapentaenoate
ID INSULIN-SECRETION; CANCER CELLS; DIABETIC-NEPHROPATHY; LIPID-METABOLISM;
SKELETAL-MUSCLE; GENE-EXPRESSION; CYCLE ARREST; TUMOR-CELLS;
FATTY-ACIDS; LXR-ALPHA
AB Saturated fatty acids are implicated in the development of diabetes via the impairment of pancreatic islet beta-cell viability and function. Liver X receptors (LXRs) and eicosapentaenoate (EPA) are known regulators of fatty acid metabolism. However, their roles in the pathogenesis of diabetes remain incompletely understood. The aim of this study was to determine the effects of EPA and the LXR agonist T0901317 on saturated fatty acid (palmitic acid)-induced apoptosis in the insulinoma beta-cell line INS-1, a model for insulin-secreting beta-cells. T0901317 significantly promoted palmitic acid-induced apoptotic cell death in the INS-1 cells. Consistent with these results, caspase-3 activity and BAX and sterol regulatory element binding protein-1c (SREBP-1c) mRNA levels were markedly increased in INS-1 cells co-administered palmitic acid and T0901317. The production of reactive oxygen species was considerably higher in the cells cultured concurrently with T0901317 and palmitic acid than in the cells incubated with either agent alone. EPA treatment attenuated the cellular death promoted by palmitic acid and T0901317 in the INS-1 cells, disclosing a possible mediating mechanism involving the inhibition of SREBP-1c. Finally, T0901317 up-regulated the palmitic acid-induced expression of p27(KIP1), transforming growth factor beta 1, and SMAD3 proteins in INS-1 cells. These results demonstrate that palmitic acid-induced apoptosis in beta-cells is enhanced by T0901317 via the activation of LXRs and is blocked by EPA via the inhibition of SREBP-1c, suggesting that the regulation of lipogenesis and lipotoxicity affecting pancreatic beta-cell viability and insulin production may be a unique strategy for diabetes therapy.
C1 [Liang, Huasheng; Zhong, Yuhua; Zhou, Shaobi] Guangxi Med Univ, Hosp 9, Beihai Inst Endocrine & Metab Dis, Beihai 536000, Guangxi, Peoples R China.
[Li, Qingdi Quentin] NIAID, NIH, Bethesda, MD 20892 USA.
RP Zhong, YH (reprint author), Guangxi Med Univ, Hosp 9, Beihai Inst Endocrine & Metab Dis, Beihai 536000, Guangxi, Peoples R China.
EM zhongyh111@163.com; liquenti@niaid.nih.gov
FU Science and Technology Commission Foundation of Guangxi Province
[0991294]
FX This study was supported by a grant from the Applied Basic Research
Programs of Science and Technology Commission Foundation of Guangxi
Province (No. 0991294).
NR 51
TC 12
Z9 13
U1 0
U2 6
PU INT INST ANTICANCER RESEARCH
PI ATHENS
PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22,
ATHENS 19014, GREECE
SN 0258-851X
J9 IN VIVO
JI In Vivo
PD SEP-OCT
PY 2011
VL 25
IS 5
BP 711
EP 718
PG 8
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 792MY
UT WOS:000292752400001
PM 21753123
ER
PT J
AU Evans, S
Fleming, SM
Dolan, RJ
Averbeck, BB
AF Evans, Simon
Fleming, Stephen M.
Dolan, Raymond J.
Averbeck, Bruno B.
TI Effects of Emotional Preferences on Value-based Decision-making Are
Mediated by Mentalizing and Reward Networks
SO JOURNAL OF COGNITIVE NEUROSCIENCE
LA English
DT Article
ID VENTROMEDIAL PREFRONTAL CORTEX; ORBITOFRONTAL CORTEX;
BEHAVIORAL-CONTROL; BRAIN; VALUATION; ATTENTION; SYSTEMS; HUMANS;
METAANALYSIS; COGNITION
AB Real-world decision-making often involves social considerations. Consequently, the social value of stimuli can induce preferences in choice behavior. However, it is unknown how financial and social values are integrated in the brain. Here, we investigated how smiling and angry face stimuli interacted with financial reward feedback in a stochastically rewarded decision-making task. Subjects reliably preferred the smiling faces despite equivalent reward feedback, demonstrating a socially driven bias. We fit a Bayesian reinforcement learning model to factor the effects of financial rewards and emotion preferences in individual subjects, and regressed model predictions on the trial-by-trial fMRI signal. Activity in the subcallosal cingulate and the ventral striatum, both involved in reward learning, correlated with financial reward feedback, whereas the differential contribution of social value activated dorsal temporo-parietal junction and dorsal anterior cingulate cortex, previously proposed as components of a mentalizing network. We conclude that the impact of social stimuli on value-based decision processes is mediated by effects in brain regions partially separable from classical reward circuitry.
C1 [Averbeck, Bruno B.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
[Evans, Simon; Fleming, Stephen M.; Dolan, Raymond J.; Averbeck, Bruno B.] UCL Inst Neurol, London, England.
RP Averbeck, BB (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 49,Room 1B80,49 Convent Dr,MSC 4415, Bethesda, MD 20892 USA.
EM bruno.averbeck@nih.gov
OI Dolan, Ray/0000-0001-9356-761X
FU Wellcome Trust; MRC within UCL; NIH, National Institute of Mental Health
FX We thank all the volunteers who participated in this study. This work
was supported by a Wellcome Trust Programme Grant to R. J. D., MRC
funding within the UCL 4-Year PhD in Neuroscience to S. M. F. This work
was supported in part by the Intramural Program of the NIH, National
Institute of Mental Health.
NR 43
TC 11
Z9 11
U1 4
U2 18
PU MIT PRESS
PI CAMBRIDGE
PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA
SN 0898-929X
J9 J COGNITIVE NEUROSCI
JI J. Cogn. Neurosci.
PD SEP
PY 2011
VL 23
IS 9
BP 2197
EP 2210
DI 10.1162/jocn.2010.21584
PG 14
WC Neurosciences; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA 789IK
UT WOS:000292508900009
PM 20946058
ER
PT J
AU Maldonado, H
Ramirez, E
Utreras, E
Pando, ME
Kettlun, AM
Chiong, M
Kulkarni, AB
Collados, L
Puente, J
Cartier, L
Valenzuela, MA
AF Maldonado, Horacio
Ramirez, Eugenio
Utreras, Elias
Pando, Maria E.
Kettlun, Ana M.
Chiong, Mario
Kulkarni, Ashok B.
Collados, Lucia
Puente, Javier
Cartier, Luis
Valenzuela, Maria A.
TI Inhibition of Cyclin-Dependent Kinase 5 but Not of Glycogen Synthase
Kinase 3-beta Prevents Neurite Retraction and Tau Hyperphosphorylation
Caused by Secretable Products of Human T-Cell Leukemia Virus Type
I-Infected Lymphocytes
SO JOURNAL OF NEUROSCIENCE RESEARCH
LA English
DT Article
DE HAM/TSP; MT-2; SH-SY5Y; CDK5-siRNA; Tax
ID HTLV-I; LYSOPHOSPHATIDIC ACID; CEREBROSPINAL-FLUID; ALZHEIMERS-DISEASE;
NEURODEGENERATIVE DISEASES; SH-SY5Y CELLS; PHOSPHORYLATION; PROTEIN;
DEGENERATION; PATHOLOGY
AB Human T-cell leukemia virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurodegenerative disease characterized by selective loss of axons and myelin in the corticospinal tracts. This central axonopathy may originate from the impairment of anterograde axoplasmic transport. Previous work showed tau hyperphosphorylation at T(181) in cerebrospinal fluid of HAM/TSP patients. Similar hyperphosphorylation occurs in SH-SY5Y cells incubated with supernatant from MT-2 cells (HTLV-I-infected lymphocytes secreting viral proteins, including Tax) that produce neurite shortening. Tau phosphorylation at T 181 is attributable to glycogen synthase kinase 3-beta (GSK3-beta) and cyclin-dependent kinase 5 (CDK5) activation. Here we investigate whether neurite retraction in the SH-SY5Y model associates with concurrent changes in other tau hyperphosphorylable residues. Threonine 181 turned out to be the only tau hyperphosphorylated residue. We also evaluate the role of GSK3-beta and CDK5 in this process by using specific kinase inhibitors (LiCl, TDZD-8, and roscovitine). Changes in both GSK3-beta active and inactive forms were followed by measuring the regulatory phosphorylable sites (S(9) and Y(216), inactivating and activating phosphorylation, respectively) together with changes in beta-catenin protein levels. Our results showed that LiCl and TDZD-8 were unable to prevent MT-2 supernatant-mediated neurite retraction and also that neither Y(216) nor S(9) phosphorylations were changed in GSK3-beta. Thus, GSK3-beta seems not to play a role in T 181 hyperphosphorylation. On the other hand, the CDK5 involvement in tau phosphorylation was confirmed by both the increase in its enzymatic activity and the absence of MT-2 neurite retraction in the presence of roscovitine or CDK5 siRNA transfection. (C) 2011 Wiley-Liss, Inc.
C1 [Maldonado, Horacio; Pando, Maria E.; Kettlun, Ana M.; Chiong, Mario; Collados, Lucia; Puente, Javier; Valenzuela, Maria A.] Univ Chile, Fac Ciencias Quim & Farmaceut, Dept Bioquim & Biol Mol, Santiago, Chile.
[Ramirez, Eugenio] Univ Chile, Fac Med, Dept Virol, Programa Virol, Santiago 7, Chile.
[Utreras, Elias; Kulkarni, Ashok B.] NIDCR, Funct Genom Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD USA.
[Cartier, Luis] Univ Chile, Fac Med, Dept Ciencias Neurol, Santiago 7, Chile.
RP Valenzuela, MA (reprint author), Univ Chile, Fac Ciencias Quim & Farmaceut, Dept Bioquim & Biol Mol, Casilla 233, Santiago, Chile.
EM mavalenz@uchile.cl
RI utreras, elias/I-1038-2013; Chiong, Mario/I-1043-2013
OI utreras, elias/0000-0002-1004-0466; Chiong, Mario/0000-0002-5174-6545
FU FONDECYT [108-0396]
FX Contract grant sponsor: FONDECYT; Contract grant number: 108-0396.
NR 48
TC 13
Z9 14
U1 1
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0360-4012
J9 J NEUROSCI RES
JI J. Neurosci. Res.
PD SEP
PY 2011
VL 89
IS 9
BP 1489
EP 1498
DI 10.1002/jnr.22678
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 790QM
UT WOS:000292604300016
PM 21671254
ER
PT J
AU Roth, BL
AF Roth, Bryan L.
TI Irving Page Lecture: 5-HT2A serotonin receptor biology: Interacting
proteins, kinases and paradoxical regulation
SO NEUROPHARMACOLOGY
LA English
DT Review
DE PDZ domain; Functional selectivity; Antipsychotic; Psychoactive; RSK2;
Caveolin
ID RAT CEREBRAL-CORTEX; KETANSERIN RECOGNITION SITES; SMOOTH-MUSCLE-CELLS;
5-HYDROXYTRYPTAMINE(2A) RECEPTOR; FUNCTIONAL SELECTIVITY; ACID
DIETHYLAMIDE; BINDING-SITES; IN-VITRO; SIGNAL-TRANSDUCTION; PREFRONTAL
CORTEX
AB 5-hydroxytryptamine(2A) (5-HT2A) serotonin receptors are important pharmacological targets for a large number of central nervous system and peripheral serotonergic medications. In this review article I summarize work mainly from my lab regarding serotonin receptor anatomy, pharmacology, signaling and regulation. I highlight the role of serotonin receptor interacting proteins and the emerging paradigm of G-protein coupled receptor functional selectivity.
This article is part of a Special Issue entitled 'Serotonin: The New Wave'. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Roth, Bryan L.] Univ N Carolina, Dept Pharmacol, Sch Med, Program Neurosci,Lineberger Canc Ctr,NIMH Psychoa, Chapel Hill, NC 27514 USA.
[Roth, Bryan L.] Univ N Carolina, Div Med Chem & Nat Prod, Sch Med, Chapel Hill, NC 27514 USA.
RP Roth, BL (reprint author), Univ N Carolina, Dept Pharmacol, Sch Med, Program Neurosci,Lineberger Canc Ctr,NIMH Psychoa, Room 4072,Genet Med Bldg, Chapel Hill, NC 27514 USA.
EM bryan_roth@med.unc.edu
RI Roth, Bryan/F-3928-2010
FU NIH [RO1MH61887, U19MH82441]; Michael Hooker Distinguished Chair of
Pharmacology; NARSAD
FX This work was supported in part by grants and contracts from the NIH
(RO1MH61887, U19MH82441, the NIMH Psychoactive Drug Screening Program),
the Michael Hooker Distinguished Chair of Pharmacology and a NARSAD
Distinguished Investigator Award.
NR 120
TC 21
Z9 21
U1 2
U2 14
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD SEP
PY 2011
VL 61
IS 3
SI SI
BP 348
EP 354
DI 10.1016/j.neuropharm.2011.01.012
PG 7
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 791OD
UT WOS:000292673600002
PM 21288474
ER
PT J
AU Peterson, KM
Guo, XT
Elkahloun, AG
Mondal, D
Bardhan, PK
Sugawara, A
Duggal, P
Haque, R
Petri, WA
AF Peterson, Kristine M.
Guo, Xiaoti
Elkahloun, Abdel G.
Mondal, Dinesh
Bardhan, Pradip K.
Sugawara, Akira
Duggal, Priya
Haque, Rashidul
Petri, William A., Jr.
TI The expression of REG 1A and REG 1B is increased during acute amebic
colitis
SO PARASITOLOGY INTERNATIONAL
LA English
DT Article
DE Entamoeba histolytica; Regenerating gene (REG) 1; Apoptosis
ID I-ALPHA PROTEIN; INFLAMMATORY-BOWEL-DISEASE; ENTAMOEBA-HISTOLYTICA;
ULCERATIVE-COLITIS; GENE-EXPRESSION; GASTRIC-CANCER; UP-REGULATION;
CELLS; MUCOSA; PROLIFERATION
AB Entamoeba histolytica, a protozoan parasite, is an important cause of diarrhea and colitis in the developing world. Amebic colitis is characterized by ulceration of the intestinal mucosa. We performed microarray analysis of intestinal biopsies during acute and convalescent amebiasis in order to identify genes potentially involved in tissue injury or repair. Colonic biopsy samples were obtained from 8 patients during acute E. histolytica colitis and again 60 days after recovery. Gene expression in the biopsies was evaluated using microarray, and confirmed by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). REG 1A and REG 1B were the most upregulated of all genes in the human intestine in acute versus convalescent E. histolytica disease: as determined by microarray, the levels of induction were 7.4-fold and 10.7 fold for REG 1A and B; p = 0.003 and p = 0.006 respectively. Increased expression of REG 1A and REG 1B protein in the colonic crypt epithelial cells during acute amebiasis was similarly observed by immunohistochemistry. Because REG 1 protein is anti-apoptotic and pro-proliferative, and since E. histolytica induces apoptosis of the intestinal epithelium as part of its disease process, we next tested if REG 1 might be protective during amebiasis by preventing parasite-induced apoptosis. Intestinal epithelial cells from REG 1 -/- mice were found to be more susceptible to spontaneous, and parasite-induced, apoptosis in vitro (p = 0.03). We concluded that REG 1A and REG 1B were upregulated during amebiasis and may function to protect the intestinal epithelium from parasite-induced apoptosis. Published by Elsevier Ireland Ltd.
C1 [Peterson, Kristine M.; Guo, Xiaoti; Petri, William A., Jr.] Univ Virginia, Div Infect Dis & Int Hlth, Charlottesville, VA USA.
[Elkahloun, Abdel G.] Natl Human Genome Inst, NIH, Baltimore, MD USA.
[Mondal, Dinesh; Bardhan, Pradip K.; Haque, Rashidul] ICDDR B, Dhaka, Bangladesh.
[Sugawara, Akira] Tohoku Univ, Grad Sch Med, Sendai, Miyagi 980, Japan.
[Duggal, Priya] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
RP Peterson, KM (reprint author), Univ Virginia Hlth Syst, POB 801340,Bldg MR6,Crispell Dr, Charlottesville, VA 22908 USA.
EM kmp5v@virginia.edu
FU National Institutes of Health [AI-43596, K08A1072470]; intramural
division of the National Human Genome Research Institute, National
Institutes of Health
FX We thank Patcharin Pramoonjago for her assistance with
immunohistochemistry. This work was supported by grant AI-43596 (to WP)
and K08A1072470 (to KP) from the National Institutes of Health, and also
funded in part by the intramural division of the National Human Genome
Research Institute, National Institutes of Health.
NR 29
TC 16
Z9 16
U1 1
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1383-5769
J9 PARASITOL INT
JI Parasitol. Int.
PD SEP
PY 2011
VL 60
IS 3
BP 296
EP 300
DI 10.1016/j.parint.2011.04.005
PG 5
WC Parasitology
SC Parasitology
GA 791OF
UT WOS:000292673800010
PM 21586335
ER
PT J
AU Zheng, G
Yuan, A
Jeffries, N
AF Zheng, Gang
Yuan, Ao
Jeffries, Neal
TI Hybrid Bayes factors for genome-wide association studies when a robust
test is used
SO COMPUTATIONAL STATISTICS & DATA ANALYSIS
LA English
DT Article
DE Bayesian model averaging; Bayes factors; Genetic models; Genome-wide
scan and ranking; Posterior weighted likelihood; Profile likelihood
ID GENETIC ASSOCIATION; SAMPLE-SIZE; RISK LOCI; MODELS; SCANS
AB Bayes factor (BF) is often used to measure evidence against the null hypothesis in Bayesian hypothesis testing. In the analysis of genome-wide association (GWA) studies, extreme BF values support the associations detected based on significant p-values. Results from recent GWA studies are presented, which show that existing BFs may not be consistent with p-values when a robust test is used due to using different genetic models in the BF and p-value approaches and this may result in misleading conclusions. Two hybrid BFs, which combine the advantages of both the frequentist and Bayesian methods, are then proposed for the markers showing at least moderate associations (p-value < 10(-5)) based on a robust test. One is Bayesian model averaging using a posterior weighted likelihood and the other is the maximum BF using a profile likelihood. The proposed hybrid BFs and p-values of robust tests do not depend on a single genetic model, but instead, consolidate information over a set of models. We compare the hybrid BFs with two existing BF approaches, including an existing Bayesian model averaging method, in terms of false and true positive rates by simulations. The results show that, for markers showing at least moderate associations, both the hybrid BFs have higher true positive rates than the two existing BFs, while all false positive rates are similar. Applications of the two hybrid BFs to the markers associated with bipolar disorder, type 2 diabetes and age-related macular degeneration are presented. Our hybrid BFs provide better and more robust measures to compare significantly associated markers within and across GWA studies. Published by Elsevier B.V.
C1 [Zheng, Gang; Jeffries, Neal] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
[Yuan, Ao] Howard Univ, Natl Human Genome Ctr, Washington, DC 20059 USA.
RP Zheng, G (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr, Bethesda, MD 20892 USA.
EM zhengg@nhlbi.nih.gov
NR 16
TC 0
Z9 0
U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-9473
EI 1872-7352
J9 COMPUT STAT DATA AN
JI Comput. Stat. Data Anal.
PD SEP 1
PY 2011
VL 55
IS 9
BP 2698
EP 2711
DI 10.1016/j.csda.2011.03.021
PG 14
WC Computer Science, Interdisciplinary Applications; Statistics &
Probability
SC Computer Science; Mathematics
GA 781FN
UT WOS:000291916100013
ER
PT J
AU Oh, U
Fujita, M
Ikonomidou, VN
Evangelou, IE
Matsuura, E
Harberts, E
Ohayon, J
Pike, VW
Zhang, Y
Zoghbi, SS
Innis, RB
Jacobson, S
AF Oh, Unsong
Fujita, Masahiro
Ikonomidou, Vasiliki N.
Evangelou, Iordanis E.
Matsuura, Eiji
Harberts, Erin
Ohayon, Joan
Pike, Victor W.
Zhang, Yi
Zoghbi, Sami S.
Innis, Robert B.
Jacobson, Steven
TI Translocator Protein PET Imaging for Glial Activation in Multiple
Sclerosis
SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY
LA English
DT Article
DE Multiple sclerosis; Translocator protein; PET; Glial activation
ID POSITRON-EMISSION-TOMOGRAPHY; BENZODIAZEPINE-RECEPTOR; IN-VIVO; BRAIN;
BINDING; INFLAMMATION; RADIOLIGAND; MICROGLIA; BIOMARKER; LESIONS
AB Glial activation in the setting of central nervous system inflammation is a key feature of the multiple sclerosis (MS) pathology. Monitoring glial activation in subjects with MS, therefore, has the potential to be informative with respect to disease activity. The translocator protein 18 kDa (TSPO) is a promising biomarker of glial activation that can be imaged by positron emission tomography (PET). To characterize the in vivo TSPO expression in MS, we analyzed brain PET scans in subjects with MS and healthy volunteers in an observational study using [(11)C]PBR28, a newly developed translocator protein-specific radioligand. The [(11)C]PBR28 PET showed altered compartmental distribution of TSPO in the MS brain compared to healthy volunteers (p = 0.019). Focal increases in [(11)C]PBR28 binding corresponded to areas of active inflammation as evidenced by significantly greater binding in regions of gadolinium contrast enhancement compared to contralateral normal-appearing white matter (p = 0.0039). Furthermore, increase in [(11)C]PBR28 binding preceded the appearance of contrast enhancement on magnetic resonance imaging in some lesions, suggesting a role for early glial activation in MS lesion formation. Global [(11)C]PBR28 binding showed correlation with disease duration (p = 0.041), but not with measures of clinical disability. These results further define TSPO as an informative marker of glial activation in MS.
C1 [Oh, Unsong; Evangelou, Iordanis E.; Harberts, Erin; Ohayon, Joan; Jacobson, Steven] Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
[Fujita, Masahiro; Pike, Victor W.; Zhang, Yi; Zoghbi, Sami S.; Innis, Robert B.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
[Ikonomidou, Vasiliki N.] George Mason Univ, Dept Elect & Comp Engn, Volgenau Sch Informat Technol & Engn, Fairfax, VA 22030 USA.
[Matsuura, Eiji] Kagoshima Univ Grad Sch Med & Dent Sci, Dept Neurol & Geriatr, Kagoshima, Japan.
RP Jacobson, S (reprint author), Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, NIH, 10 Ctr Dr,Bldg 10 Rm 5C103, Bethesda, MD 20892 USA.
EM jacobsons@ninds.nih.gov
RI MATSUURA, EIJI/E-1231-2013
OI MATSUURA, EIJI/0000-0001-8215-8853
FU NIH (NINDS and NIMH)
FX We thank Maria Ferraris Araneta (MIB/NIMH) and Kaylan Fenton (NIB/NINDS)
for clinical support. This research was supported by the Intramural
Research Program of the NIH (NINDS and NIMH).
NR 17
TC 42
Z9 42
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1557-1890
J9 J NEUROIMMUNE PHARM
JI J. Neuroimmune Pharm.
PD SEP
PY 2011
VL 6
IS 3
BP 354
EP 361
DI 10.1007/s11481-010-9243-6
PG 8
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 786MQ
UT WOS:000292312900004
PM 20872081
ER
PT J
AU Cohen, S
Stemmer, SM
Zozulya, G
Ochaion, A
Patoka, R
Barer, F
Bar-Yehuda, S
Rath-Wolfson, L
Jacobson, KA
Fishman, P
AF Cohen, S.
Stemmer, S. M.
Zozulya, G.
Ochaion, A.
Patoka, R.
Barer, F.
Bar-Yehuda, S.
Rath-Wolfson, L.
Jacobson, K. A.
Fishman, P.
TI CF102 an A(3) Adenosine Receptor Agonist Mediates Anti-Tumor and
Anti-Inflammatory Effects in the Liver
SO JOURNAL OF CELLULAR PHYSIOLOGY
LA English
DT Article
ID NF-KAPPA-B; ADJUVANT-INDUCED ARTHRITIS; TUMOR-NECROSIS-FACTOR;
HUMAN-MELANOMA CELLS; IB-MECA; RHEUMATOID-ARTHRITIS;
HEPATOCELLULAR-CARCINOMA; CONCANAVALIN-A; CANCER-THERAPY; GROWTH
INHIBITION
AB The Gi protein-associated A(3) adenosine receptor (A(3)AR) is a member of the adenosine receptor family. Selective agonists at the A(3)AR, such as CF101 and CF102 were found to induce anti-inflammatory and anti-cancer effects. In this study, we examined the differential effect of CF102 in pathological conditions of the liver. The anti-inflammatory protective effect of CF101 was tested in a model of liver inflammation induced by Concanavalin A (Con. A) and the anti-cancer effect of CF102 was examined in vitro and in a xenograft animal model utilizing Hep-3B hepatocellular carcinoma (HCC) cells. The mechanism of action was explored by following the expression levels of key signaling proteins in the inflamed and tumor liver tissues, utilizing Western blot (WB) analysis. In the liver inflammation model, CF102 (100 mu g/kg) markedly reduced the secretion of serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase in comparison to the vehicle-treated group. Mechanistically, CF102 treatment decreased the expression level of phosphorylated glycogen synthase kinase-3 beta, NF-kappa B, and TNF-alpha and prevented apoptosis in the liver. This was demonstrated by decreased expression levels of Fas receptor (FasR) and of the pro-apoptotic proteins Bax and Bad in liver tissues. In addition, CF102-induced apoptosis of Hep-3B cells both in vitro and in vivo via de-regulation of the PI3K-NF-kappa B signaling pathway, resulting in up-regulation of pro-apoptotic proteins. Taken together, CF102 acts as a protective agent in liver inflammation and inhibits HCC tumor growth. These results suggest that CF102 through its differential effect is a potential drug candidate to treat various pathological liver conditions. J. Cell. Physiol. 226: 2438-2447, 2011. (C) 2010 Wiley-Liss, Inc.
C1 [Cohen, S.; Zozulya, G.; Ochaion, A.; Patoka, R.; Barer, F.; Bar-Yehuda, S.; Fishman, P.] Can Fite BioPharma Ltd, IL-49170 Kiryat Matalon, Petach Tikva, Israel.
[Stemmer, S. M.] Tel Aviv Univ, Davidoff Ctr, Rabin Med Ctr, Inst Oncol,Sackler Sch Med, Petah Tiqwa, Israel.
[Rath-Wolfson, L.] Tel Aviv Univ, Dept Pathol, Rabin Med Ctr, Sackler Fac Med, Petah Tiqwa, Israel.
[Jacobson, K. A.] NIDDKD, NIH, Bethesda, MD 20892 USA.
RP Fishman, P (reprint author), Can Fite BioPharma Ltd, 10 Bareket St,POB 7537, IL-49170 Kiryat Matalon, Petach Tikva, Israel.
EM pnina@canfite.co.il
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU Intramural NIH HHS [Z99 DK999999, ZIA DK031117-23]
NR 57
TC 21
Z9 22
U1 1
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0021-9541
J9 J CELL PHYSIOL
JI J. Cell. Physiol.
PD SEP
PY 2011
VL 226
IS 9
BP 2438
EP 2447
DI 10.1002/jcp.22593
PG 10
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 778FY
UT WOS:000291689700026
PM 21660967
ER
PT J
AU McCarthy, J
Lochner, A
Opie, LH
Sack, MN
Essop, MF
AF McCarthy, Joy
Lochner, Amanda
Opie, Lionel H.
Sack, Michael N.
Essop, M. Faadiel
TI PKC epsilon Promotes Cardiac Mitochondrial and Metabolic Adaptation to
Chronic Hypobaric Hypoxia by GSK3 beta Idnhibition
SO JOURNAL OF CELLULAR PHYSIOLOGY
LA English
DT Article
ID PROTEIN-KINASE-C; GLYCOGEN-SYNTHASE KINASE-3-BETA; RIGHT-VENTRICULAR
HYPERTROPHY; PERMEABILITY TRANSITION PORE; HIGH-ALTITUDE HYPOXIA;
INDUCED HEART-FAILURE; ISCHEMIA-REPERFUSION; GENE-EXPRESSION;
FATTY-ACID; RAT-HEART
AB PKC epsilon is central to cardioprotection. Sub-proteome analysis demonstrated co-localization of activated cardiac PKC epsilon (aPKC epsilon) with metabolic, mitochondrial, and cardioprotective modulators like hypoxia-inducible factor 1 alpha (HIF-1 alpha). aPKC epsilon relocates to the mitochondrion, inactivating glycogen synthase kinase 3 beta (GSK3 beta) to modulate glycogen metabolism, hypertrophy and HIF-1 alpha. However, there is no established mechanistic link between PKC epsilon, p-GSK3 beta and HIF1-alpha. Here we hypothesized that cardiac-restricted aPKC epsilon improves mitochondrial response to hypobaric hypoxia by altered substrate fuel selection via a GSK3 beta/HIF-1 alpha-dependent mechanism. aPKC epsilon and wild-type (WT) mice were exposed to 14 days of hypobaric hypoxia (45 kPa, 11% O(2)) and cardiac metabolism, functional parameters, p-GSK3 beta/HIF-1 alpha expression, mitochondrial function and ultrastructure analyzed versus normoxic controls. Mitochondrial ADP-dependent respiration, ATP production and membrane potential were attenuated in hypoxic WT but maintained in hypoxic aPKC epsilon mitochondria (P < 0.005, n = 8). Electron microscopy revealed a hypoxia-associated increase in mitochondrial number with ultrastructural disarray in WT versus aPKCe hearts. Concordantly, left ventricular work was diminished in hypoxic WT but not aPKC epsilon mice (glucose only perfusions). However, addition of palmitate abrogated this (P < 0.05 vs. WT). aPKC epsilon hearts displayed increased glucose utilization at baseline and with hypoxia. In parallel, p-GSK3 beta and HIF1-alpha peptide levels were increased in hypoxic aPKC epsilon hearts versus WT. Our study demonstrates that modest, sustained PKC epsilon activation blunts cardiac pathophysiologic responses usually observed in response to chronic hypoxia. Moreover, we propose that preferential glucose utilization by PKC epsilon hearts is orchestrated by a p-GSK3 beta/HIF-1 alpha-mediated mechanism, playing a crucial role to sustain contractile function in response to chronic hypobaric hypoxia. J. Cell. Physiol. 226: 2457-2468, 2011. (C) 2010 Wiley-Liss, Inc.
C1 [McCarthy, Joy; Opie, Lionel H.] Univ Cape Town, Sch Med, Hatter Inst Cardiovasc Res, ZA-7925 Cape Town, South Africa.
[Lochner, Amanda] Univ Stellenbosch, Fac Hlth Sci, Dept Med Physiol, ZA-7505 Tygerberg, South Africa.
[Sack, Michael N.] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
[Essop, M. Faadiel] CMRG, Dept Physiol Sci, Stellenbosch, South Africa.
RP McCarthy, J (reprint author), Univ Cape Town, Sch Med, Hatter Inst Cardiovasc Res, ZA-7925 Cape Town, South Africa.
EM joy.mccarthy@uct.ac.za
FU South African MRC; South African National Research Foundation
FX The University of Cape Town Electron Microscopy Unit for assistance, Ms
Sonia Genade for the working mouse heart perfusions and Dr. Heinrich
Taegtmeyer (Houston, TX, USA) for quantitative RT-PCR analysis performed
in his laboratory. We further acknowledge the South African MRC and the
South African National Research Foundation for financial support, and
Dr. Uthra Rajamani for formatting of the figures.
NR 69
TC 11
Z9 11
U1 0
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0021-9541
J9 J CELL PHYSIOL
JI J. Cell. Physiol.
PD SEP
PY 2011
VL 226
IS 9
BP 2457
EP 2468
DI 10.1002/jcp.22592
PG 12
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 778FY
UT WOS:000291689700028
PM 21660969
ER
PT J
AU Hu, ZH
Follmann, DA
Qin, J
AF Hu, Zonghui
Follmann, Dean A.
Qin, Jing
TI Dimension reduced kernel estimation for distribution function with
incomplete data
SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE
LA English
DT Article
DE Curse of dimensionality; Dimension reduction; Distribution function;
Ignorable missingness; Kernel regression; Quantile
ID AUXILIARY INFORMATION
AB This work focuses on the estimation of distribution functions with incomplete data, where the variable of interest Y has ignorable missingness but the covariate X is always observed. When X is high dimensional, parametric approaches to incorporate X-information is encumbered by the risk of model misspecification and nonparametric approaches by the curse of dimensionality. We propose a semiparametric approach, which is developed under a nonparametric kernel regression framework, but with a parametric working index to condense the high dimensional X-information for reduced dimension. This kernel dimension reduction estimator has double robustness to model misspecification and is most efficient if the working index adequately conveys the X-information about the distribution of Y. Numerical studies indicate better performance of the semiparametric estimator over its parametric and nonparametric counterparts. We apply the kernel dimension reduction estimation to an HIV study for the effect of antiretroviral therapy on HIV virologic suppression. Published by Elsevier B.V.
C1 [Hu, Zonghui; Follmann, Dean A.; Qin, Jing] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
RP Hu, ZH (reprint author), NIAID, Biostat Res Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM huzo@niaid.nih.gov; dfollmann@niaid.nih.gov; jqin@niaid.nih.gov
FU Intramural NIH HHS [Z99 AI999999]
NR 18
TC 3
Z9 3
U1 1
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-3758
J9 J STAT PLAN INFER
JI J. Stat. Plan. Infer.
PD SEP
PY 2011
VL 141
IS 9
BP 3084
EP 3093
DI 10.1016/j.jspi.2011.03.030
PG 10
WC Statistics & Probability
SC Mathematics
GA 776GS
UT WOS:000291523100009
PM 21731174
ER
PT J
AU Liu, Y
AF Liu, Yuan
TI The DIADEM and Beyond
SO NEUROINFORMATICS
LA English
DT Editorial Material
C1 NINDS, NIH, Bethesda, MD 20892 USA.
RP Liu, Y (reprint author), NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM liuyuan@ninds.nih.gov
NR 19
TC 18
Z9 18
U1 0
U2 1
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1539-2791
J9 NEUROINFORMATICS
JI Neuroinformatics
PD SEP
PY 2011
VL 9
IS 2-3
SI SI
BP 99
EP 102
DI 10.1007/s12021-011-9102-5
PG 4
WC Computer Science, Interdisciplinary Applications; Neurosciences
SC Computer Science; Neurosciences & Neurology
GA 771OS
UT WOS:000291171200002
PM 21431331
ER
PT J
AU Gillette, TA
Brown, KM
Svoboda, K
Liu, Y
Ascoli, GA
AF Gillette, Todd A.
Brown, Kerry M.
Svoboda, Karel
Liu, Yuan
Ascoli, Giorgio A.
TI DIADEMchallenge.Org: A Compendium of Resources Fostering the Continuous
Development of Automated Neuronal Reconstruction
SO NEUROINFORMATICS
LA English
DT Editorial Material
C1 [Gillette, Todd A.; Brown, Kerry M.; Ascoli, Giorgio A.] George Mason Univ, Ctr Neural Informat Struct & Plast, Krasnow Inst Adv Study, Fairfax, VA 22030 USA.
[Svoboda, Karel] Howard Hughes Med Inst, Ashburn, VA USA.
[Liu, Yuan] NINDS, NIH, Bethesda, MD 20892 USA.
RP Ascoli, GA (reprint author), George Mason Univ, Ctr Neural Informat Struct & Plast, Krasnow Inst Adv Study, Fairfax, VA 22030 USA.
EM ascoli@gmu.edu
OI Gillette, Todd/0000-0001-6896-4824
NR 2
TC 13
Z9 13
U1 1
U2 4
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1539-2791
J9 NEUROINFORMATICS
JI Neuroinformatics
PD SEP
PY 2011
VL 9
IS 2-3
SI SI
BP 303
EP 304
DI 10.1007/s12021-011-9104-3
PG 2
WC Computer Science, Interdisciplinary Applications; Neurosciences
SC Computer Science; Neurosciences & Neurology
GA 771OS
UT WOS:000291171200019
ER
PT J
AU Barry, CS
Backus, KM
Barry, CE
Davis, BG
AF Barry, Conor S.
Backus, Keriann M.
Barry, Clifton E., III
Davis, Benjamin G.
TI ESI-MS Assay of M. tuberculosis Cell Wall Antigen 85 Enzymes Permits
Substrate Profiling and Design of a Mechanism-Based Inhibitor
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID MYCOBACTERIUM-TUBERCULOSIS; GLYCOSYLTRANSFERASES; INACTIVATION;
PURIFICATION; GLYCOSIDES; SMEGMATIS; ENVELOPE; SYNTHASE; ANALOGS
AB Mycobacterium tuberculosis Antigen 85 enzymes are vital to the integrity of the highly impermeable cell envelope and are potential therapeutic targets. Kinetic analysis using a label-free assay revealed both mechanistic details and a substrate profile that allowed the design and construction of a selective in vitro mechanism-based inhibitor.
C1 [Backus, Keriann M.; Barry, Clifton E., III] US Natl Inst Allergy & Infect Dis, TB Res Sect, Lab Clin Infect Dis, Bethesda, MD USA.
[Barry, Conor S.; Backus, Keriann M.; Davis, Benjamin G.] Univ Oxford, Dept Chem, Chem Res Lab, Oxford OX1 3TA, England.
RP Barry, CE (reprint author), US Natl Inst Allergy & Infect Dis, TB Res Sect, Lab Clin Infect Dis, Bethesda, MD USA.
EM cbarry@niaid.nih.gov; Ben.Davis@chem.ox.ac.uk
RI Barry, III, Clifton/H-3839-2012; Davis, Benjamin/C-5281-2011
OI Davis, Benjamin/0000-0002-5056-407X
FU National Institutes of Health, National Institute of Allergy and
Infectious Disease; Rhodes Trust; Biotechnology and Biological Sciences
Research Council; Bill and Melinda Gates Foundation; Royal Society
FX This work was funded by the Intramural Research Program of the National
Institutes of Health, National Institute of Allergy and Infectious
Disease (C.E.B.), the Rhodes Trust (K.M.B.), the Biotechnology and
Biological Sciences Research Council (C.S.B.), and the Bill and Melinda
Gates Foundation through the TB Drug Accelerator Program (C.E.B,
B.G.D.). B.G.D. is a Royal Society Wolfson Research Merit Award
recipient. We thank Colorado State "TB Vaccine Testing and Research
Materials" contract for providing Antigen 85 plasmids.
NR 27
TC 13
Z9 13
U1 1
U2 7
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD AUG 31
PY 2011
VL 133
IS 34
BP 13232
EP 13235
DI 10.1021/ja204249p
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA 829BZ
UT WOS:000295551600007
PM 21776980
ER
PT J
AU Goldova, J
Ulrych, A
Hercik, K
Branny, P
AF Goldova, Jana
Ulrych, Ales
Hercik, Kamil
Branny, Pavel
TI A eukaryotic-type signalling system of Pseudomonas aeruginosa
contributes to oxidative stress resistance, intracellular survival and
virulence
SO BMC GENOMICS
LA English
DT Article
ID SERINE/THREONINE PROTEIN-KINASE; SER/THR KINASE;
MYCOBACTERIUM-TUBERCULOSIS; TRANSCRIPTOME ANALYSIS; HYDROGEN-PEROXIDE;
BIOFILM FORMATION; ESCHERICHIA-COLI; GENE-EXPRESSION;
FUNCTIONAL-CHARACTERIZATION; ALLOSTERIC ACTIVATION
AB Background: The genome of Pseudomonas aeruginosa contains at least three genes encoding eukaryotic-type Ser/Thr protein kinases, one of which, ppkA, has been implicated in P. aeruginosa virulence. Together with the adjacent pppA phosphatase gene, they belong to the type VI secretion system (H1-T6SS) locus, which is important for bacterial pathogenesis. To determine the biological function of this protein pair, we prepared a pppA-ppkA double mutant and characterised its phenotype and transcriptomic profiles.
Results: Phenotypic studies revealed that the mutant grew slower than the wild-type strain in minimal media and exhibited reduced secretion of pyoverdine. In addition, the mutant had altered sensitivity to oxidative and hyperosmotic stress conditions. Consequently, mutant cells had an impaired ability to survive in murine macrophages and an attenuated virulence in the plant model of infection. Whole-genome transcriptome analysis revealed that pppA-ppkA deletion affects the expression of oxidative stress-responsive genes, stationary phase sigma-factor RpoS-regulated genes, and quorum-sensing regulons. The transcriptome of the pppA-ppkA mutant was also analysed under conditions of oxidative stress and showed an impaired response to the stress, manifested by a weaker induction of stress adaptation genes as well as the genes of the SOS regulon. In addition, expression of either RpoS-regulated genes or quorum-sensing-dependent genes was also affected. Complementation analysis confirmed that the transcription levels of the differentially expressed genes were specifically restored when the pppA and ppkA genes were expressed ectopically.
Conclusions: Our results suggest that in addition to its crucial role in controlling the activity of P. aeruginosa H1-T6SS at the post-translational level, the PppA-PpkA pair also affects the transcription of stress-responsive genes. Based on these data, it is likely that the reduced virulence of the mutant strain results from an impaired ability to survive in the host due to the limited response to stress conditions.
C1 [Goldova, Jana; Ulrych, Ales; Hercik, Kamil; Branny, Pavel] Acad Sci Czech Republic, Inst Microbiol, Cell & Mol Microbiol Div, Vvi, CR-14220 Prague 4, Czech Republic.
[Hercik, Kamil] NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA.
RP Branny, P (reprint author), Acad Sci Czech Republic, Inst Microbiol, Cell & Mol Microbiol Div, Vvi, Videnska 1083, CR-14220 Prague 4, Czech Republic.
EM branny@biomed.cas.cz
RI Branny, Pavel/H-2490-2014; Ulrych, Ales/J-8048-2014; Goldova,
Jana/J-8258-2014
FU Czech Science Foundation [204/08/0783]; Grant Agency of the Charles
University in Prague [161/2006/B-BIO/PrF]; [AV0Z50200510]
FX We are grateful to Thilo Kohler (University of Geneva) for the gift of
P. aeruginosa PAO1 wild type strain and Herbert P. Schweizer (Colorado
State University) for the gift of plasmids pEX18Ap, pFLP2, pPS858,
pUC18-mini-Tn7T-LAC and pTNS2. This work was supported by the Czech
Science Foundation (grant no. 204/08/0783 to PB), the Grant Agency of
the Charles University in Prague (Project no. 161/2006/B-BIO/PrF to JG)
and by Institutional Research Concept grant AV0Z50200510.
NR 83
TC 17
Z9 18
U1 1
U2 21
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD AUG 31
PY 2011
VL 12
AR 437
DI 10.1186/1471-2164-12-437
PG 21
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 827GC
UT WOS:000295415500001
PM 21880152
ER
PT J
AU Alves, G
Yu, YK
AF Alves, Gelio
Yu, Yi-Kuo
TI Combining Independent, Weighted P-Values: Achieving Computational
Stability by a Systematic Expansion with Controllable Accuracy
SO PLOS ONE
LA English
DT Article
ID MULTIPLE END-POINTS; SIGNIFICANCE TESTS; CLINICAL-TRIALS; COMBINATION;
PROBABILITIES; DISTRIBUTIONS; VARIABLES; STATISTICS; SEARCHES; EVENTS
AB Given the expanding availability of scientific data and tools to analyze them, combining different assessments of the same piece of information has become increasingly important for social, biological, and even physical sciences. This task demands, to begin with, a method-independent standard, such as the P-value, that can be used to assess the reliability of a piece of information. Good's formula and Fisher's method combine independent P-values with respectively unequal and equal weights. Both approaches may be regarded as limiting instances of a general case of combining P-values from m groups; P-values within each group are weighted equally, while weight varies by group. When some of the weights become nearly degenerate, as cautioned by Good, numeric instability occurs in computation of the combined P-values. We deal explicitly with this difficulty by deriving a controlled expansion, in powers of differences in inverse weights, that provides both accurate statistics and stable numerics. We illustrate the utility of this systematic approach with a few examples. In addition, we also provide here an alternative derivation for the probability distribution function of the general case and show how the analytic formula obtained reduces to both Good's and Fisher's methods as special cases. A C++ program, which computes the combined P-values with equal numerical stability regardless of whether weights are (nearly) degenerate or not, is available for download at our group website http://www.ncbi.nlm.nih.gov/CBBresearch/Yu/downloads/CoinedPValues.html.
C1 [Alves, Gelio; Yu, Yi-Kuo] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
RP Alves, G (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
EM yyu@ncbi.nlm.nih.gov
FU National Library of Medicine at the National Institutes of Health/DHHS
FX This work was supported by the Intramural Research Program of the
National Library of Medicine at the National Institutes of Health/DHHS.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 44
TC 3
Z9 3
U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 31
PY 2011
VL 6
IS 8
AR e22647
DI 10.1371/journal.pone.0022647
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 817NM
UT WOS:000294680800003
PM 21912585
ER
PT J
AU Gao, JJ
Huang, XM
Park, Y
Hollenbeck, A
Chen, HL
AF Gao, Jianjun
Huang, Xuemei
Park, YikYung
Hollenbeck, Albert
Chen, Honglei
TI An Exploratory Study on CLU, CR1 and PICALM and Parkinson Disease
SO PLOS ONE
LA English
DT Article
ID APOLIPOPROTEIN-E GENOTYPE; GENOME-WIDE ASSOCIATION; ALZHEIMERS-DISEASE;
CLUSTERIN/APOLIPOPROTEIN-J; IDENTIFIES VARIANTS; RISK; DEMENTIA;
AGGREGATION; CHOLESTEROL; RELATIVES
AB Background: Recent GWAS and subsequent confirmation studies reported several single-nucleotide polymorphisms (SNPs) at the CLU, CR1 and PICALM loci in association with late-onset Alzheimer's disease (AD). Parkinson disease (PD) shares several clinical and pathologic characteristics with AD; we therefore explored whether these SNPs were also associated with PD risk.
Methodology/Principal Findings: 791 non-Hispanic Whites cases and 1,580 matched controls were included in the study. Odds ratios (OR) and 95% confidence intervals (CI) were obtained from logistic regression models. rs11136000 at the CLU locus was associated with PD risk under the recessive model (comparing TT versus CC+CT: OR = 0.71, 95% CI: 0.55-0.92, p = 0.008) after adjusting for year of birth, gender, smoking, and caffeine intake. Further adjustment for family history of PD and ApoE epsilon 4 status did not change the result. In addition, we did not find evidence for effect modification by ApoE or known PD risk factors. The association, however, appeared to be stronger for PD with dementia (OR = 0.49, 95% CI: 0.27-0.91) than for PD without dementia (OR = 0.81, 95% CI: 0.61-1.06). The two other SNPs, rs6656401 from CR1, and rs3851179 from PICALM region were not associated with PD (p > 0.05).
Conclusion: Our exploratory analysis suggests an association of CLU with PD. This exploratory finding and the role of dementia in explaining this finding needs further investigation.
C1 [Gao, Jianjun; Chen, Honglei] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurol, Hershey, PA 17033 USA.
[Park, YikYung] NCI, Nutr Epidemiol Branch, Rockville, MD USA.
[Hollenbeck, Albert] AARP, Washington, DC USA.
RP Gao, JJ (reprint author), Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, Res Triangle Pk, NC 27709 USA.
EM chenh2@niehs.nih.gov
OI Chen, Honglei/0000-0003-3446-7779; Park, Yikyung/0000-0002-6281-489X
FU NIH; National Institute of Environmental Health Sciences
[Z01-ES-101986]; National Cancer Institute [Z01 CP010196-02]
FX This study was supported by the intramural research program of the NIH,
the National Institute of Environmental Health Sciences (Z01-ES-101986)
and the National Cancer Institute (Z01 CP010196-02). The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript. None of the authors have financial
conflict of interest.
NR 34
TC 13
Z9 13
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 30
PY 2011
VL 6
IS 8
AR e24211
DI 10.1371/journal.pone.0024211
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 817MS
UT WOS:000294678300031
PM 21912625
ER
PT J
AU Pecsi, I
Szabo, JE
Adams, SD
Simon, I
Sellers, JR
Vertessy, BG
Toth, J
AF Pecsi, Ildiko
Szabo, Judit E.
Adams, Scott D.
Simon, Istvan
Sellers, James R.
Vertessy, Beata G.
Toth, Judit
TI Nucleotide pyrophosphatase employs a P-loop-like motif to enhance
catalytic power and NDP/NTP discrimination
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE NTP hydrolysis; nucleotide discrimination; dUTP pyrophosphatase; Walker
A motif; evolutionary adaptation
ID BIFUNCTIONAL DCTP DEAMINASE; PHOSPHATE ESTER HYDROLYSIS; DIMERIC
DUTPASE-DUDPASE; INFECTIOUS-ANEMIA VIRUS; MYOSIN MOTOR DOMAIN; X-RAY
STRUCTURES; ESCHERICHIA-COLI; ACTIVE-SITE; CRYSTAL-STRUCTURE; C-TERMINUS
AB We investigated the potential (d)NDP/(d)NTP discrimination mechanisms in nucleotide pyrophosphatases. Here, we report that dUTPase, an essential nucleotide pyrophosphatase, uses a C-terminal P-loop-like sequence in a unique mechanism for substrate discrimination and efficient hydrolysis. Our spectroscopy and transient kinetics results on human dUTPase mutants combined with previous structural studies indicate that (i) H-bond interactions between the gamma-phosphate and the P-loop-like motif V promote the catalytically competent conformation of the reaction center at the alpha-phosphate group; (ii) these interactions accelerate the chemical step of the kinetic cycle and that (iii) hydrolysis occurs very slowly or not at all in the absence of the gamma-phosphate-motif V interactions, i.e., in dUDP, dUDP.BeFx, or in the motif V-deleted mutant. The physiological role of dUTPase is to set cellular dUTP: dTTP ratios and prevent injurious uracil incorporation into DNA. Based upon comparison with related pyrophosphate generating (d)NTPases, we propose that the unusual use of a P-loop-like motif enables dUTPases to achieve efficient catalysis of dUTP hydrolysis and efficient discrimination against dUDP at the same time. These specifics might have been advantageous on the appearance of uracil-DNA repair. The similarities and differences between dUTPase motif V and the P-loop (or Walker A sequence) commonly featured by ATP- and GTPases offer insight into functional adaptation to various nucleotide hydrolysis tasks.
C1 [Pecsi, Ildiko; Szabo, Judit E.; Adams, Scott D.; Simon, Istvan; Vertessy, Beata G.; Toth, Judit] Hungarian Acad Sci, Biol Res Ctr, Inst Enzymol, H-1113 Budapest, Hungary.
[Adams, Scott D.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Sellers, James R.; Toth, Judit] NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA.
[Vertessy, Beata G.] Budapest Univ Technol & Econ, Dept Appl Biotechnol, H-1111 Budapest, Hungary.
RP Vertessy, BG (reprint author), Hungarian Acad Sci, Biol Res Ctr, Inst Enzymol, Karolina Ut 29, H-1113 Budapest, Hungary.
EM vertessy@enzim.hu; tothj@enzim.hu
RI Vertessy, Beata/H-6202-2012; Simon, Istvan/A-2868-2008
FU US National Institutes of Health [1R01TW008130-01]; Hungarian Academy of
Sciences; Howard Hughes Medical Institutes [55000342]; Hungarian
Scientific Research Funds [PD72008, CK-78646, K68229, K72973, NI68466];
National Office for Research and Technology, Hungary
[JAP_TSZ_071128_TB_INTER]; EU [SPINE2c LSHG-CT-2006-031220, TEACH-SG
LSSG-CT-2007-037198]; Alexander von Humboldt Foundation
FX This work was supported by the US National Institutes of Health (Grant
number 1R01TW008130-01); the Janos Bolyai Research Scholarship of the
Hungarian Academy of Sciences, the Howard Hughes Medical Institutes
(Grant number 55000342); the Hungarian Scientific Research Funds (Grant
numbers PD72008, CK-78646, K68229, K72973, and NI68466); the National
Office for Research and Technology, Hungary (Grant number
JAP_TSZ_071128_TB_INTER) and the EU FP6 (Grant numbers SPINE2c
LSHG-CT-2006-031220, TEACH-SG LSSG-CT-2007-037198) and the Alexander von
Humboldt Foundation.
NR 34
TC 16
Z9 16
U1 0
U2 9
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD AUG 30
PY 2011
VL 108
IS 35
BP 14437
EP 14442
DI 10.1073/pnas.1013872108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 814DH
UT WOS:000294425900021
PM 21831832
ER
PT J
AU Feng, HQ
Zhou, Z
Zhou, BR
Bai, YW
AF Feng, Hanqiao
Zhou, Zheng
Zhou, Bing-Rui
Bai, Yawen
TI Structure of the budding yeast Saccharomyces cerevisiae centromeric
histones Cse4-H4 complexed with the chaperone Scm3
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Letter
ID RECOGNITION
C1 [Feng, Hanqiao; Zhou, Zheng; Zhou, Bing-Rui; Bai, Yawen] NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Bai, YW (reprint author), NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM yawen@helix.nih.gov
RI Zhou, Bing-Rui/D-4766-2009
NR 2
TC 8
Z9 8
U1 0
U2 2
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD AUG 30
PY 2011
VL 108
IS 35
BP E596
EP E596
DI 10.1073/pnas.1109548108
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 814DH
UT WOS:000294425900002
PM 21844330
ER
PT J
AU Ascierto, ML
De Giorgi, V
Liu, QZ
Bedognetti, D
Spivey, TL
Murtas, D
Uccellini, L
Ayotte, BD
Stroncek, DF
Chouchane, L
Manjili, MH
Wang, E
Marincola, FM
AF Ascierto, Maria Libera
De Giorgi, Valeria
Liu, Qiuzhen
Bedognetti, Davide
Spivey, Tara L.
Murtas, Daniela
Uccellini, Lorenzo
Ayotte, Ben D.
Stroncek, David F.
Chouchane, Lotfi
Manjili, Masoud H.
Wang, Ena
Marincola, Francesco M.
TI An immunologic portrait of cancer
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Review
ID TUMOR-INFILTRATING LYMPHOCYTES; REGULATORY T-CELLS; NF-KAPPA-B; SEROUS
OVARIAN-CANCER; INDEPENDENT PROGNOSTIC-FACTOR; HUMAN COLORECTAL-CANCER;
PROSTATE-CANCER; BREAST-CANCER; MALIGNANT-MELANOMA; IMMUNE-RESPONSES
AB The advent of high-throughput technology challenges the traditional histopathological classification of cancer, and proposes new taxonomies derived from global transcriptional patterns. Although most of these molecular reclassifications did not endure the test of time, they provided bulk of new information that can reframe our understanding of human cancer biology. Here, we focus on an immunologic interpretation of cancer that segregates oncogenic processes independent from their tissue derivation into at least two categories of which one bears the footprints of immune activation. Several observations describe a cancer phenotype where the expression of interferon stimulated genes and immune effector mechanisms reflect patterns commonly observed during the inflammatory response against pathogens, which leads to elimination of infected cells. As these signatures are observed in growing cancers, they are not sufficient to entirely clear the organism of neoplastic cells but they sustain, as in chronic infections, a self-perpetuating inflammatory process. Yet, several studies determined an association between this inflammatory status and a favorable natural history of the disease or a better responsiveness to cancer immune therapy. Moreover, these signatures overlap with those observed during immune-mediated cancer rejection and, more broadly, immune-mediated tissue-specific destruction in other immune pathologies. Thus, a discussion concerning this cancer phenotype is warranted as it remains unknown why it occurs in immune competent hosts. It also remains uncertain whether a genetically determined response of the host to its own cancer, the genetic makeup of the neoplastic process or a combination of both drives the inflammatory process. Here we reflect on commonalities and discrepancies among studies and on the genetic or somatic conditions that may cause this schism in cancer behavior.
C1 [Ascierto, Maria Libera; De Giorgi, Valeria; Liu, Qiuzhen; Bedognetti, Davide; Spivey, Tara L.; Murtas, Daniela; Uccellini, Lorenzo; Stroncek, David F.; Wang, Ena; Marincola, Francesco M.] NIH, IDIS, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Ascierto, Maria Libera; De Giorgi, Valeria; Liu, Qiuzhen; Bedognetti, Davide; Spivey, Tara L.; Murtas, Daniela; Uccellini, Lorenzo; Stroncek, David F.; Wang, Ena; Marincola, Francesco M.] NIH, Trans NIH Ctr Human Immunol CHI, Bethesda, MD 20892 USA.
[Ascierto, Maria Libera] Univ Genoa, Dept Internal Med, I-16126 Genoa, Italy.
[Ascierto, Maria Libera; Bedognetti, Davide] CEBR, Genoa, Italy.
[Bedognetti, Davide] Natl Canc Res Inst Genoa, Genoa, Italy.
[Ayotte, Ben D.] No Michigan Univ, Dept Biol, Marquette, MI 49855 USA.
[Manjili, Masoud H.] Virginia Commonwealth Univ, Massey Canc Ctr, Dept Microbiol & Immunol, Richmond, VA 23298 USA.
RP Marincola, FM (reprint author), NIH, IDIS, Dept Transfus Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM fmarincola@mail.cc.nih.gov
RI duan, hf/F-9166-2011; Bedognetti, Davide/A-9090-2012; Ascierto, Maria
Libera/A-9239-2012; De Giorgi, Valeria/D-4582-2017;
OI Bedognetti, Davide/0000-0002-5857-773X
NR 131
TC 45
Z9 45
U1 2
U2 19
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD AUG 29
PY 2011
VL 9
AR 146
DI 10.1186/1479-5876-9-146
PG 13
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 822NI
UT WOS:000295054700001
PM 21875439
ER
PT J
AU Blanford, S
Shi, WP
Christian, R
Marden, JH
Koekemoer, LL
Brooke, BD
Coetzee, M
Read, AF
Thomas, MB
AF Blanford, Simon
Shi, Wangpeng
Christian, Riann
Marden, James H.
Koekemoer, Lizette L.
Brooke, Basil D.
Coetzee, Maureen
Read, Andrew F.
Thomas, Matthew B.
TI Lethal and Pre-Lethal Effects of a Fungal Biopesticide Contribute to
Substantial and Rapid Control of Malaria Vectors
SO PLOS ONE
LA English
DT Article
ID CELLULAR DEFENSE RESPONSE; ANOPHELES-GAMBIAE-S.S.; ADULT AEDES-AEGYPTI;
ANISOPLIAE IP 46; METARHIZIUM-ANISOPLIAE; ENTOMOPATHOGENIC FUNGUS;
BEAUVERIA-BASSIANA; INSECTICIDE RESISTANCE; SCHISTOCERCA-GREGARIA;
MOSQUITO RESISTANCE
AB Rapidly emerging insecticide resistance is creating an urgent need for new active ingredients to control the adult mosquitoes that vector malaria. Biopesticides based on the spores of entomopathogenic fungi have shown considerable promise by causing very substantial mortality within 7-14 days of exposure. This mortality will generate excellent malaria control if there is a high likelihood that mosquitoes contact fungi early in their adult lives. However, where contact rates are lower, as might result from poor pesticide coverage, some mosquitoes will contact fungi one or more feeding cycles after they acquire malaria, and so risk transmitting malaria before the fungus kills them. Critics have argued that 'slow acting' fungal biopesticides are, therefore, incapable of delivering malaria control in real-world contexts. Here, utilizing standard WHO laboratory protocols, we demonstrate effective action of a biopesticide much faster than previously reported. Specifically, we show that transient exposure to clay tiles sprayed with a candidate biopesticide comprising spores of a natural isolate of Beauveria bassiana, could reduce malaria transmission potential to zero within a feeding cycle. The effect resulted from a combination of high mortality and rapid fungal-induced reduction in feeding and flight capacity. Additionally, multiple insecticide-resistant lines from three key African malaria vector species were completely susceptible to fungus. Thus, fungal biopesticides can block transmission on a par with chemical insecticides, and can achieve this where chemical insecticides have little impact. These results support broadening the current vector control paradigm beyond fast-acting chemical toxins.
C1 [Blanford, Simon; Read, Andrew F.] Penn State Univ, Dept Biol, Mueller Lab, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Blanford, Simon; Shi, Wangpeng; Read, Andrew F.; Thomas, Matthew B.] Penn State Univ, Dept Entomol, Merkle Lab, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Shi, Wangpeng] China Agr Univ, Minist Agr, Key Lab Biol Control, Beijing 100094, Peoples R China.
[Christian, Riann; Koekemoer, Lizette L.; Brooke, Basil D.; Coetzee, Maureen] Natl Inst Communicable Dis, Natl Hlth Lab Serv, Vector Control Reference Unit, Johannesburg, South Africa.
[Christian, Riann; Koekemoer, Lizette L.; Brooke, Basil D.; Coetzee, Maureen] Univ Witwatersrand, Fac Hlth Sci, Sch Pathol, Malaria Entomol Res Unit, Johannesburg, South Africa.
[Read, Andrew F.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Blanford, S (reprint author), Penn State Univ, Dept Biol, Mueller Lab, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
EM mbt13@psu.edu
FU Gates Grand Challenges Explorations [53066]; National Institutes of
Health [AI088094-01]; Innovative Vector Control Consortium; China
Scholarship Council; Pennsylvania Department of Health
FX This research was part-funded by grants from Gates Grand Challenges
Explorations (No. 53066), the National Institutes of Health
(AI088094-01), the Innovative Vector Control Consortium, and a China
Scholarship Council Grant to WP. This project was also funded, in part,
under a grant with the Pennsylvania Department of Health using Tobacco
Settlement Funds. The Department specifically disclaims responsibility
for any analyses, interpretations or conclusions. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 61
TC 31
Z9 31
U1 2
U2 28
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 29
PY 2011
VL 6
IS 8
AR e23591
DI 10.1371/journal.pone.0023591
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 817MF
UT WOS:000294676900009
PM 21897846
ER
PT J
AU Austin, C
AF Austin, Christopher
TI Translational therapeutics development at NIH
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Austin, Christopher] NIH, NIH Ctr Translat Therapeut, Bethesda, MD 20892 USA.
EM austinc@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 166-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378304468
ER
PT J
AU Betzig, E
Planchon, T
Gao, L
Davidson, M
Galbraith, J
Galbraith, C
AF Betzig, Eric
Planchon, Thomas
Gao, Liang
Davidson, Michael
Galbraith, James
Galbraith, Catherine
TI Rapid 3D isotropic imaging of living cells using Bessel beam plane
illumination
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Betzig, Eric; Planchon, Thomas; Gao, Liang; Davidson, Michael] Janelia Farm HHMI, Ashburn, VA 20147 USA.
[Galbraith, James] NINDS, Bethesda, MD 20892 USA.
[Galbraith, Catherine] NICHHD, Bethesda, MD 20892 USA.
EM betzige@janelia.hhmi.org
NR 0
TC 0
Z9 0
U1 0
U2 11
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 297-PHYS
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378306074
ER
PT J
AU Bienstock, RJ
Wang, JL
Tomer, KB
Deterding, LJ
AF Bienstock, Rachelle J.
Wang, Jinglan
Tomer, Kenneth B.
Deterding, Leesa J.
TI Structure prediction of the RNA binding La autoantigen protein through
computational docking of protein domain structures with Mass
Spectrometry (MS) experimental constraints
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Bienstock, Rachelle J.; Wang, Jinglan; Tomer, Kenneth B.; Deterding, Leesa J.] NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA.
EM rachelleb1@gmail.com
NR 4
TC 0
Z9 0
U1 1
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 354-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378302291
ER
PT J
AU Bryant, S
AF Bryant, Stephen
TI Open repository for chemical structure and biological activity
information
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Bryant, Stephen] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
EM bryant@ncbi.nlm.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 54-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378302313
ER
PT J
AU Chan, M
DeVito, MJ
Shafer, T
Hughes, MF
AF Chan, Melissa
DeVito, Michael J.
Shafer, Timothy
Hughes, Michael F.
TI Evaluating tools and models used for quantitative extrapolation of in
vitro to in vivo data for neurotoxicants
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Chan, Melissa; DeVito, Michael J.] NIEHS, Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA.
[Shafer, Timothy; Hughes, Michael F.] US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA.
EM chanp2@niehs.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 236-AGRO
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378300353
ER
PT J
AU Chung, HS
Eaton, WA
AF Chung, Hoi Sung
Eaton, William A.
TI Single-molecule FRET and transition paths in protein folding
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Chung, Hoi Sung; Eaton, William A.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM chunghoi@niddk.nih.gov
NR 0
TC 0
Z9 0
U1 1
U2 7
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 400-PHYS
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378306180
ER
PT J
AU Collins, F
Austin, CP
AF Collins, Francis
Austin, Christopher P.
TI Catalyzing opportunities in translational research
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Collins, Francis; Austin, Christopher P.] NIH, Bethesda, MD 20892 USA.
EM austinc@mail.nih.gov
NR 0
TC 0
Z9 0
U1 1
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 223-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378304531
ER
PT J
AU Deflorian, F
Jacobson, KA
AF Deflorian, Francesca
Jacobson, Kenneth A.
TI Comparison of three GPCR structural templates for modeling of the
P2Y(12) nucleotide receptor
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Deflorian, Francesca; Jacobson, Kenneth A.] NIH, Bioorgan Chem Lab, Bethesda, MD 20892 USA.
EM deflorianf@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 197-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378302129
ER
PT J
AU Fritz, J
Arora, K
Boshoff, HIM
Plotkin, BJ
Green, J
Konaklieva, M
AF Fritz, Juliana
Arora, Kriti
Boshoff, Helena I. M.
Plotkin, Balbina J.
Green, Jacalyn
Konaklieva, Monika
TI Effect of the aryl ring heteroatom attached at C4 on the antimicrobial
activity of N-carbamylated b-Lactams
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Fritz, Juliana; Konaklieva, Monika] American Univ, Dept Chem, Washington, DC 20016 USA.
[Arora, Kriti; Boshoff, Helena I. M.] NIAID, Dept TB Res, NIH, LCID, Bethesda, MD 20892 USA.
[Plotkin, Balbina J.; Green, Jacalyn] Midwestern Univ, Dept Microbiol & Immunol, Chicago, IL 60515 USA.
EM jf9075a@gmail.com
NR 0
TC 0
Z9 0
U1 0
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 308-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378304619
ER
PT J
AU Ganesan, V
Liang, FT
Shock, D
Beard, W
Wilson, S
Cho, B
AF Ganesan, Vaidyanathan
Liang, Fengting
Shock, David
Beard, William
Wilson, Samuel
Cho, Bongsup
TI Solution structure studies of aminofluorene-DNA adduct complexed with
Klenow fragment and DNA polymerase beta
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Ganesan, Vaidyanathan; Liang, Fengting; Cho, Bongsup] Univ Rhode Isl, Dept Biomed & Pharmaceut Sci, Kingston, RI 02881 USA.
[Shock, David; Beard, William; Wilson, Samuel] NIEHS, Struct Biol Lab, NIH, Bethesda, MD 20892 USA.
EM vaidychem@yahoo.com
NR 0
TC 0
Z9 0
U1 0
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 51-TOXI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378307517
ER
PT J
AU Gangjee, A
Zaware, N
Mooberry, SL
Hamel, E
AF Gangjee, Aleem
Zaware, Nilesh
Mooberry, Susan L.
Hamel, Ernest
TI Synthesis and biological evaluation of
N-4-(substitutedphenyl)-N-4-methyl/desmethyl-9H-pyrimido[4,5-b]indole-2,
4-diamines as antimitotic agents
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Gangjee, Aleem; Zaware, Nilesh] Duquesne Univ, Grad Sch Pharmaceut Sci, Pittsburgh, PA 15217 USA.
[Mooberry, Susan L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA.
[Hamel, Ernest] NIH, Screening Technol Branch, Frederick, MD 21702 USA.
EM nileshpharm@yahoo.com
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 52-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378304713
ER
PT J
AU Gangjee, A
Zaware, N
Devambatla, RKV
Mooberry, SL
Hamel, E
AF Gangjee, Aleem
Zaware, Nilesh
Devambatla, Ravi Kumar Vyas
Mooberry, Susan L.
Hamel, Ernest
TI Synthesis and biological evaluation of
5-chloro-N-4-substituted-N-4-methyl-9H-pyrimido[4,5-b]indole-2,4-diamine
s as antimitotic agents
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Gangjee, Aleem; Zaware, Nilesh; Devambatla, Ravi Kumar Vyas] Duquesne Univ, Div Med Chem, Pittsburgh, PA 15282 USA.
[Mooberry, Susan L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA.
[Hamel, Ernest] NCI, Div Canc Treatment & Diag, Frederick, MD 21702 USA.
EM drk_vyas@yahoo.co.in
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 53-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378304714
ER
PT J
AU Gangjee, A
Zhao, Y
Raghavan, S
Mooberry, SL
Hamel, E
AF Gangjee, Aleem
Zhao, Ying
Raghavan, Sudhir
Mooberry, Susan L.
Hamel, Ernest
TI Synthesis and biological evaluation of the R- and S-enantiomers of the
antitubulin 6-methyl cyclopenta[d]pyrimidines as cytotoxic agents that
parallel predicted antitubulin activities
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Gangjee, Aleem; Zhao, Ying; Raghavan, Sudhir] Duquesne Univ, Grad Sch Pharmaceut Sci, Pittsburgh, PA 15282 USA.
[Mooberry, Susan L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA.
[Hamel, Ernest] NCI, NIH, Frederick, MD 21702 USA.
EM gangjee@duq.edu
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 269-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378304580
ER
PT J
AU Gerhold, D
Dieterle, F
Ozer, J
Holder, D
Troth, S
Glaab, W
Bailey, W
Sistare, F
AF Gerhold, David
Dieterle, Frank
Ozer, Josef
Holder, Daniel
Troth, Sean
Glaab, Warren
Bailey, Wendy
Sistare, Frank
TI Kidney injury biomarkers in urine: From rats to regulatory approvals
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Gerhold, David] NIH, Chem Genom Ctr, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
[Gerhold, David; Ozer, Josef; Troth, Sean; Glaab, Warren; Bailey, Wendy; Sistare, Frank] Merck & Co Inc, Safety Assessment Mol & Investigat Toxicol, West Point, PA 19486 USA.
[Dieterle, Frank] Novartis Pharmaceut, Global Program Diagnost, Basel, Switzerland.
[Holder, Daniel] Merck Co Inc, Dept Biometr, West Point, PA 19486 USA.
EM david.gerhold@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 36-TOXI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378307502
ER
PT J
AU Horkay, F
Basser, PJ
Hecht, AM
Geissler, E
AF Horkay, Ferenc
Basser, Peter J.
Hecht, Anne-Marie
Geissler, Erik
TI Biological self-assembly and nanoscale interactions in aggrecan
solutions
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Horkay, Ferenc; Basser, Peter J.] NIH, Sect Tissue Biophys & Biomimet, Bethesda, MD 20892 USA.
[Hecht, Anne-Marie; Geissler, Erik] Univ J Fourier Grenoble, Spectrometrie Phys Lab, St Martin Dheres, France.
EM horkay@helix.nih.gov
RI Basser, Peter/H-5477-2011
NR 0
TC 0
Z9 0
U1 0
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 165-POLY
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378306748
ER
PT J
AU Horkay, F
Horkayne-Szakaly, I
Dimitriadis, EK
Silva, C
Basser, PJ
AF Horkay, Ferenc
Horkayne-Szakaly, Iren
Dimitriadis, Emilios K.
Silva, Candida
Basser, Peter J.
TI Molecular biomechanics of cartilage
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Horkay, Ferenc; Horkayne-Szakaly, Iren; Silva, Candida; Basser, Peter J.] NIH, Sect Tissue Biophys & Biomimet, Bethesda, MD 20892 USA.
[Dimitriadis, Emilios K.] NIBIB, NIH, Bethesda, MD 20892 USA.
EM horkay@helix.nih.gov
RI Basser, Peter/H-5477-2011
NR 0
TC 0
Z9 0
U1 0
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 151-BIOL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378300703
ER
PT J
AU Hughes, MF
Starr, JM
Scollon, EJ
DeVito, MJ
AF Hughes, Michael F.
Starr, James M.
Scollon, Edward J.
DeVito, Michael J.
TI In vitro and in vivo experimental data for pyrethroid pharmacokinetic
models: The case of bifenthrin
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Hughes, Michael F.] US EPA, Off Res & Dev, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA.
[Starr, James M.] US EPA, Off Res & Dev, Natl Exposure Res Lab, Res Triangle Pk, NC 27711 USA.
[Scollon, Edward J.] US EPA, Off Pesticide Programs, Div Hlth Effects, Washington, DC 20460 USA.
[DeVito, Michael J.] NIEHS, Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA.
EM hughes.michaelf@epa.gov
NR 0
TC 0
Z9 0
U1 0
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 214-AGRO
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378300330
ER
PT J
AU Iyer, MR
Dersch, CM
Rothman, RB
Jacobson, AE
Rice, KC
AF Iyer, Malliga R.
Dersch, Christina M.
Rothman, Richard B.
Jacobson, Arthur E.
Rice, Kenner C.
TI Probes for narcotic receptor mediated phenomena: Effect of C4a alkyl and
ar-alkyl chain length on the opioid receptor affinity of N-methyl
cis-4a-substituted 1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Iyer, Malliga R.; Jacobson, Arthur E.; Rice, Kenner C.] NIDA, Drug Design & Synth Sect, Chem Biol Res Branch, Rockville, MD 20852 USA.
[Dersch, Christina M.; Rothman, Richard B.] NIDA, Clin Psychopharmacol Sect, Chem Biol Res Branch, Addict Res Ctr, Baltimore, MD 21224 USA.
EM iyerma@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 281-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378304593
ER
PT J
AU Iyer, MR
Dersch, CM
Rothman, RB
Jacobson, AE
Rice, KC
AF Iyer, Malliga R.
Dersch, Christina M.
Rothman, Richard B.
Jacobson, Arthur E.
Rice, Kenner C.
TI Probes for narcotic receptor mediated phenomena: Effect of C4a ar-alkyl
and alkyl chain length on the opioid receptor affinity of N-methyl
cis-4a-substituted 1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Iyer, Malliga R.; Jacobson, Arthur E.; Rice, Kenner C.] NIDA, Drug Design & Synth Sect, Chem Biol Res Branch, Rockville, MD 20852 USA.
[Dersch, Christina M.; Rothman, Richard B.] NIDA, Clin Psychopharmacol Sect, Chem Biol Res Branch, Addict Res Ctr, Baltimore, MD 21224 USA.
EM iyerma@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 33-AEI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378300025
ER
PT J
AU Jacobson, KA
IJzerman, AP
Auchampach, JA
Gao, ZG
AF Jacobson, Kenneth A.
IJzerman, Adriaan P.
Auchampach, John A.
Gao, Zhan-Guo
TI Allosteric modulators of the A(3) adenosine receptor
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Jacobson, Kenneth A.; Gao, Zhan-Guo] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[IJzerman, Adriaan P.] Leiden Univ, Leiden Amsterdam Ctr Drug Res, Leiden, Netherlands.
[Auchampach, John A.] Med Coll Wisconsin, Dept Pharmacol, Milwaukee, WI 53226 USA.
EM kajacobs@helix.nih.gov
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
NR 0
TC 0
Z9 0
U1 1
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 210-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378304517
ER
PT J
AU Jimenez, JL
Cubison, MJ
Ortega, AM
Hayes, PL
Farmer, DK
Day, DA
Lechner, MJ
Brune, WH
Apel, E
Diskin, GS
Fisher, JA
Fuelberg, HA
Hecobian, A
Knapp, DJ
Mikoviny, T
Riemer, D
Sachse, GW
Sessions, W
Weber, RJ
Weinheimer, AJ
Wisthaler, A
AF Jimenez, Jose L.
Cubison, Michael J.
Ortega, Amber M.
Hayes, Patrick L.
Farmer, Delphine K.
Day, Douglas A.
Lechner, Michael J.
Brune, William H.
Apel, Eric
Diskin, Glenn S.
Fisher, Jenny A.
Fuelberg, Henry A.
Hecobian, Arsineh
Knapp, David J.
Mikoviny, Tomas
Riemer, Daniel
Sachse, Glen W.
Sessions, Walter
Weber, Rodney J.
Weinheimer, Andrew J.
Wisthaler, Armin
TI Effects of aging on organic aerosol from open biomass burning smoke in
aircraft & lab studies
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Jimenez, Jose L.; Cubison, Michael J.; Ortega, Amber M.; Hayes, Patrick L.; Farmer, Delphine K.; Day, Douglas A.; Lechner, Michael J.] Univ Colorado, Dept Chem & Biochem, CIRES, Boulder, CO 80309 USA.
[Jimenez, Jose L.; Cubison, Michael J.; Ortega, Amber M.; Hayes, Patrick L.; Farmer, Delphine K.; Day, Douglas A.; Lechner, Michael J.] Univ Colorado, Dept Atmospher & Ocean Sci, Boulder, CO 80309 USA.
[Brune, William H.] Penn State Univ, University Pk, PA 16802 USA.
[Diskin, Glenn S.] NASA Langley Res Ctr, Washington, DC USA.
[Fisher, Jenny A.] Harvard Univ, Cambridge, MA 02138 USA.
[Fuelberg, Henry A.; Sessions, Walter] Florida State Univ, Tallahassee, FL 32306 USA.
[Hecobian, Arsineh; Weber, Rodney J.] Georgia Inst Technol, Atlanta, GA 30332 USA.
[Mikoviny, Tomas; Wisthaler, Armin] Univ Innsbruck, A-6020 Innsbruck, Austria.
[Riemer, Daniel] Univ Miami, Coral Gables, FL 33124 USA.
[Sachse, Glen W.] NIA, Bethesda, MD 20892 USA.
EM jose.jimenez@colorado.edu
RI Jimenez, Jose/A-5294-2008
OI Jimenez, Jose/0000-0001-6203-1847
NR 0
TC 0
Z9 0
U1 0
U2 11
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 106-PHYS
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378305764
ER
PT J
AU Jun, JH
Malhotra, SV
AF Jun, Jung Ho
Malhotra, Sanjay V.
TI Application of microwave chemistry in the etherification of heterocyclic
compounds by nucleophilic aromatic substitutions reactions (SNAr)
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Jun, Jung Ho; Malhotra, Sanjay V.] NCI, Lab Synthet Chem, SAIC Frederick Inc, Frederick, MD 21702 USA.
EM malhotrasa@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 117-ORGN
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378305008
ER
PT J
AU Kang, D
Luecke, H
AF Kang, Dongwook
Luecke, Hans
TI Development of clickable small molecule inhibitors of histone
acetyltransferases
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Kang, Dongwook; Luecke, Hans] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
EM kangdongwook@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 266-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378304577
ER
PT J
AU Klausmeyer, P
Shipley, S
McCloud, TG
Zuck, K
Newman, DJ
AF Klausmeyer, Paul
Shipley, Suzanne
McCloud, Thomas G.
Zuck, Karina
Newman, David J.
TI Spiruchostatin C, an HDAC inhibitory compound isolated from Burkholderia
thailandensis
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Klausmeyer, Paul; Shipley, Suzanne; McCloud, Thomas G.; Zuck, Karina] SAIC Frederick Inc, Nat Prod Support Grp, Frederick, MD 21702 USA.
[Newman, David J.] NCI, DTP, DCTD, Frederick, MD 21702 USA.
EM klausmeyerp@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 272-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378304584
ER
PT J
AU Kumar, A
Kumar, V
Alegria, AE
Malhotra, SV
AF Kumar, Ajay
Kumar, Vineet
Alegria, Antonio E.
Malhotra, Sanjay V.
TI Syntheses and antitumor activities on NCI-60 human tumor cell line
protocol of N-hydroxyethyl-4-aza-didehyropodophyllotoxin derivatives
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Kumar, Ajay; Alegria, Antonio E.] Univ Puerto Rico, Dept Chem, Humacao, PR 00791 USA.
[Kumar, Vineet; Malhotra, Sanjay V.] NCI, Lab Synthet Chem, SAIC Frederick Inc, Frederick, MD 21702 USA.
EM drajay_ipu@yahoo.co.in
NR 0
TC 0
Z9 0
U1 0
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 54-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378304715
ER
PT J
AU Kumar, A
Kumar, V
Alegria, AE
Malhotra, SV
AF Kumar, Ajay
Kumar, Vineet
Alegria, Antonio E.
Malhotra, Sanjay V.
TI Syntheses and antitumor activity of
N-hydroxyethyl-4-aza-didehyropodophyllotoxin derivatives
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Kumar, Ajay; Alegria, Antonio E.] Univ Puerto Rico, Dept Chem, Humacao, PR 00791 USA.
[Kumar, Vineet; Malhotra, Sanjay V.] NCI, Lab Synthet Chem, SAIC Frederick Inc, Frederick, MD 21702 USA.
EM drajaybhati@gmail.com
NR 0
TC 0
Z9 0
U1 0
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 249-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378304559
ER
PT J
AU Kumar, V
Kim, YS
Lee, S
Trepel, J
Malhotra, SV
AF Kumar, Vineet
Kim, Yeong Sang
Lee, Sunmin
Trepel, Jane
Malhotra, Sanjay V.
TI Synthesis and evaluation of novel androgen receptor inhibitors:
Potential candidates for castrate-resistant prostate cancer treatment
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Kumar, Vineet; Malhotra, Sanjay V.] NCI, Lab Synthet Chem, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Kim, Yeong Sang; Lee, Sunmin; Trepel, Jane] NCI, Med Oncol Branch, CCR, Bethesda, MD 20892 USA.
EM malhotrasa@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 247-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378304557
ER
PT J
AU Kuskovsky, R
Arora, K
Boshoff, HIM
AF Kuskovsky, Rostislav
Arora, Kriti
Boshoff, Helena I. M.
TI Synthesis of biotin-tagged b-lactams: Probes for identification of the
molecular target
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Kuskovsky, Rostislav] American Univ, Dept Chem, Washington, DC 20016 USA.
[Arora, Kriti; Boshoff, Helena I. M.] NIAID, TB Res Sect, LCID, NIH, Bethesda, MD 20892 USA.
EM rostislav4@gmail.com
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 387-ORGN
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378305279
ER
PT J
AU Lloyd, D
Plotkin, BJ
Arora, K
Boshoff, HI
Konaklieva, MI
AF Lloyd, Dina
Plotkin, Balbina J.
Arora, Kriti
Boshoff, Helena I.
Konaklieva, Monika I.
TI Effect of aryl ring fluorination on the antibacterial properties of C4
aryl-substituted b-Lactams
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Lloyd, Dina; Konaklieva, Monika I.] American Univ, Dept Chem, Washington, DC 20016 USA.
[Plotkin, Balbina J.] Midwestern Univ, Dept Microbiol & Immunol, Chicago, IL 60515 USA.
[Arora, Kriti; Boshoff, Helena I.] NIAID, TB Res Sect, LCID, NIH, Bethesda, MD 20892 USA.
EM dina.lloyd@gmail.com
NR 0
TC 0
Z9 0
U1 0
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 604-ORGN
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378305507
ER
PT J
AU Marriner, GA
Kiesewetter, DO
Mukherjee, T
Weiner, DM
Schimel, DM
Dayao, EK
Via, LE
Barry, CE
AF Marriner, Gwendolyn A.
Kiesewetter, Dale O.
Mukherjee, Tathagatha
Weiner, Danielle M.
Schimel, Daniel M.
Dayao, Emmanuel K.
Via, Laura E.
Barry, Clifton E.
TI Development of PET radiotracers based on small molecule antitubercular
drugs
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Marriner, Gwendolyn A.; Mukherjee, Tathagatha; Weiner, Danielle M.; Schimel, Daniel M.; Dayao, Emmanuel K.; Via, Laura E.; Barry, Clifton E.] NIAID, NIH, Rockville, MD 20892 USA.
[Kiesewetter, Dale O.] Natl Inst Biomed Imaging & Bioengn, NIH, Rockville, MD 20892 USA.
EM marrinerga@mail.nih.gov
RI Barry, III, Clifton/H-3839-2012
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 310-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378304622
ER
PT J
AU Mott, BT
Su, XZ
Yuan, J
Chang, CC
Maloney, DJ
Rai, G
Jadhav, A
Simeonov, A
Williams, DL
Thomas, CJ
Posner, GH
AF Mott, Bryan T.
Su, Xinzhuan
Yuan, Jing
Chang, Chin-Chien
Maloney, David J.
Rai, Ganesha
Jadhav, Ajit
Simeonov, Anton
Williams, David L.
Thomas, Craig J.
Posner, Gary H.
TI Molecules containing reactive peroxide or nitric oxide species for the
treatment of malaria
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Mott, Bryan T.; Posner, Gary H.] Johns Hopkins Univ, Dept Chem, Baltimore, MD 21218 USA.
[Mott, Bryan T.; Chang, Chin-Chien; Maloney, David J.; Rai, Ganesha; Jadhav, Ajit; Simeonov, Anton; Thomas, Craig J.] NHGRI, NIH, Chem Genom Ctr, Rockville, MD 20850 USA.
[Su, Xinzhuan; Yuan, Jing] NIAID, Lab Malaria & Vector Res, Bethesda, MD 20810 USA.
[Williams, David L.] Rush Univ, Sch Med, Dept Immunol Microbiol, Chicago, IL 60612 USA.
EM mottb@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 90-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378304753
ER
PT J
AU Nguyen, TM
Zhu, L
Kim, S
Lee, S
Chen, XY
Lee, SB
AF Nguyen, Thao M.
Zhu, Lei
Kim, Sungkyoung
Lee, Seulki
Chen, Xiaoyuan
Lee, Sang Bok
TI Conductive polymer nanotubes patch as an enhanced controlled transdermal
delivery system
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Nguyen, Thao M.; Kim, Sungkyoung; Lee, Sang Bok] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA.
[Lee, Sang Bok] Korea Adv Inst Sci & Technol, Grad Sch Nanosci & Technol, Taejon 305701, South Korea.
[Zhu, Lei; Lee, Seulki; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
EM nguyent@umd.edu
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 425-COLL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378301843
ER
PT J
AU Nussinov, R
AF Nussinov, Ruth
TI Allostery and conformational control in signaling: The ubiquitin E3
ligases
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Nussinov, Ruth] NCI, Computat Struct Biol Grp, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel.
EM ruthnu@helix.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 263-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378302196
ER
PT J
AU Okur, A
Lee, J
Brooks, BR
AF Okur, Asim
Lee, Jooyoung
Brooks, Bernard R.
TI Generating reservoir conformations for replica exchange through the use
of conformational space annealing method
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Okur, Asim; Brooks, Bernard R.] NIH, Bethesda, MD USA.
[Lee, Jooyoung] Korea Adv Inst Sci & Technol, Seoul, South Korea.
EM okura@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 123-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378302052
ER
PT J
AU Pamment, M
Malhotra, SV
AF Pamment, Michael
Malhotra, Sanjay V.
TI Novel syntheses of substituted dihydropyridones
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Pamment, Michael; Malhotra, Sanjay V.] NCI, Lab Synthet Chem, SIAC Frederick Inc, Frederick, MD 21702 USA.
EM malhotrasa@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 118-ORGN
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378305009
ER
PT J
AU Patterson, AD
Shah, YM
Gonzalez, FJ
AF Patterson, Andrew D.
Shah, Yatrik M.
Gonzalez, Frank J.
TI Mechanism and protection against acetaminophen-induced hepatotoxicity
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Patterson, Andrew D.; Shah, Yatrik M.; Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA.
EM gonzalef@mail.nih.gov
RI Patterson, Andrew/G-3852-2012
OI Patterson, Andrew/0000-0003-2073-0070
NR 0
TC 0
Z9 0
U1 0
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 13-TOXI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378307478
ER
PT J
AU Pavana, RK
Gangjee, A
Hamel, E
Mooberry, SL
AF Pavana, Roheeth K.
Gangjee, Aleem
Hamel, Ernest
Mooberry, Susan L.
TI Design, synthesis and biological evaluation of novel, conformationally
restricted, water soluble, substituted pyrrolo[3,2-d]pyrimidines as
antitubulin antitumor agents
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Pavana, Roheeth K.; Gangjee, Aleem] Duquesne Univ, Div Med Chem, Grad Sch Pharmaceut Sci, Pittsburgh, PA 15282 USA.
[Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA.
[Mooberry, Susan L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA.
EM kp.roheeth@gmail.com
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 48-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378304709
ER
PT J
AU San Jose, G
Kehn-Hall, K
Boshoff, HI
Kashanchi, F
Dowd, CS
AF San Jose, Geraldine
Kehn-Hall, Kylene
Boshoff, Helena I.
Kashanchi, Fatah
Dowd, Cynthia S.
TI Design, synthesis, and biological evaluation of novel Mtb-specific Dxr
inhibitors as potential antitubercular agents
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [San Jose, Geraldine; Dowd, Cynthia S.] George Washington Univ, Dept Chem, Washington, DC 20052 USA.
[Kehn-Hall, Kylene; Kashanchi, Fatah] George Mason Univ, Dept Mol & Microbiol, Manassa, VA 20110 USA.
[Boshoff, Helena I.] NIAID, NIH, Bethesda, MD 20892 USA.
EM gsanjose@gwu.edu
RI Kehn-Hall, Kylene/I-5752-2013
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 110-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378304414
ER
PT J
AU Sengupta, P
Talisman, T
Veatch, S
Lippincott-Schwartz, J
AF Sengupta, Prabuddha
Talisman, Tijana
Veatch, Sarah
Lippincott-Schwartz, Jennifer
TI Nano-scale spatial organization of plasma membrane revealed by
pair-correlation analysis
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Sengupta, Prabuddha; Talisman, Tijana; Lippincott-Schwartz, Jennifer] NICHD, CBMP, NIH, Bethesda, MD 20892 USA.
[Veatch, Sarah] Univ Michigan, Dept Biophys, Ann Arbor, MI 48109 USA.
EM prabuddha.sengupta@nih.gov
NR 0
TC 0
Z9 0
U1 1
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 114-PHYS
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378305772
ER
PT J
AU Talisman, IJ
Malhotra, SV
AF Talisman, Ian Jamie
Malhotra, Sanjay V.
TI Evaluation of glycosidated ginsenoside mimics as anticancer agents
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Talisman, Ian Jamie; Malhotra, Sanjay V.] NCI, Lab Synthet Chem, SAIC Frederick Inc, Frederick, MD 21702 USA.
EM malhotrasa@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 253-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378304564
ER
PT J
AU Topczewski, JJ
Beutler, JA
Wiemer, DF
AF Topczewski, Joeseph J.
Beutler, John A.
Wiemer, David F.
TI Schweinfurthins: Development of their antiproliferative activity
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Topczewski, Joeseph J.; Wiemer, David F.] Univ Iowa, Dept Chem, Iowa City, IA 52242 USA.
[Beutler, John A.] NCI, Mol Targets Dev Program, Frederick, MD 21702 USA.
EM joseph-topczewski@uiowa.edu
RI Beutler, John/B-1141-2009
OI Beutler, John/0000-0002-4646-1924
NR 0
TC 0
Z9 0
U1 0
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 195-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378304499
ER
PT J
AU Tosh, DK
Chanyshev, B
Isak, A
Chepurko, Y
Phan, K
Hochhauser, E
Shainberg, A
Jacobson, KA
AF Tosh, Dilip K.
Chanyshev, Bella
Isak, Ahuva
Chepurko, Yelena
Phan, Khai
Hochhauser, Edith
Shainberg, Asher
Jacobson, Kenneth A.
TI Discovery of novel polyamidoamine (PAMAM) dendrimer conjugated A(3)
adenosine receptor agonist ligand as a cardioprotective agent
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Tosh, Dilip K.; Phan, Khai; Jacobson, Kenneth A.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Chanyshev, Bella; Isak, Ahuva; Shainberg, Asher] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, Ramat Gan, Israel.
[Chepurko, Yelena; Hochhauser, Edith] Tel Aviv Univ, Felsenstein Med Res Ctr, Cardiac Res Lab, Petah Tiqwa, Israel.
EM toshd@mail.nih.gov
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 355-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378304669
ER
PT J
AU Tsai, DH
Elzey, S
DelRio, F
Keene, A
Tyner, K
Clogston, J
Zheng, JW
MacCuspie, R
Cho, TJ
Guha, S
Zachariah, M
Hackley, V
AF Tsai, De-Hao
Elzey, Sherrie
DelRio, Frank
Keene, Athena
Tyner, Katherine
Clogston, Jeffrey
Zheng, Jiwen
MacCuspie, Robert
Cho, Tae Joon
Guha, Suvajyoti
Zachariah, Michael
Hackley, Vincent
TI Characterization of tumor necrosis factor (TNF) protein conjugation on
gold nanoparticles
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Tsai, De-Hao; Elzey, Sherrie; DelRio, Frank; MacCuspie, Robert; Cho, Tae Joon; Guha, Suvajyoti; Zachariah, Michael; Hackley, Vincent] Natl Inst Stand & Technol, Mat Measurement Lab, Gaithersburg, MD 20899 USA.
[Keene, Athena; Tyner, Katherine] Ctr Drug Evaluat & Res Food & Drug Adm, Silver Spring, MD 20993 USA.
[Clogston, Jeffrey; Zheng, Jiwen] SAIC Frederick Inc, Nanotechnol Characterizat Lab, Adv Technol Program, NCI Frederick, Frederick, MD 21702 USA.
[Guha, Suvajyoti; Zachariah, Michael] Univ Maryland, Dept Mech Engn, College Pk, MD 20742 USA.
[Guha, Suvajyoti; Zachariah, Michael] Univ Maryland, Dept Chem, College Pk, MD 20742 USA.
EM sherrie.elzey@nist.gov
RI Tsai, De-Hao/K-6702-2012
OI Tsai, De-Hao/0000-0002-2669-3007
NR 0
TC 0
Z9 0
U1 0
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 249-COLL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378301664
ER
PT J
AU Tsai, WXL
Forbes, JG
Wang, K
AF Tsai, Wanxia L.
Forbes, Jeffrey G.
Wang, Kuan
TI Elastic scaffolding protein engineered from a SH3 binding Titin PEVK
module
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Tsai, Wanxia L.; Forbes, Jeffrey G.; Wang, Kuan] NIAMS DHHS, Muscle Biol Lab, Bethesda, MD 20892 USA.
[Wang, Kuan] Acad Sinica, Nanomed Program, Taipei 115, Taiwan.
EM liwan@exchange.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 173-BIOL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378300725
ER
PT J
AU Urick, A
Chuppa, S
Riordon, DR
Tarasova, Y
Boheler, KR
Gundry, RL
AF Urick, Amanda
Chuppa, Sandra
Riordon, Daniel R.
Tarasova, Yelena
Boheler, Kenneth R.
Gundry, Rebekah L.
TI Cell surface capturing & mass spectrometry reveal new markers for
immunophenotyping pluripotent stem cells and cardiac progenitors
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Urick, Amanda; Chuppa, Sandra; Gundry, Rebekah L.] Med Coll Wisconsin, Dept Biochem, Milwaukee, WI 53226 USA.
[Chuppa, Sandra; Gundry, Rebekah L.] Med Coll Wisconsin, Biotechnol & Bioengn Ctr, Milwaukee, WI 53226 USA.
[Riordon, Daniel R.; Tarasova, Yelena; Boheler, Kenneth R.] NIA, NIH, Baltimore, MD 21224 USA.
EM rgundry@mcw.edu
NR 0
TC 0
Z9 0
U1 1
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 154-ANYL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378300511
ER
PT J
AU Weisz, A
Mazzola, EP
Ito, Y
AF Weisz, Adrian
Mazzola, Eugene P.
Ito, Yoichiro
TI Preparative separation of 1,3,6-pyrenetrisulfonic acid from the color
additive D&C Green No. 8 using pH-zone-refining counter-current
chromatography
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Weisz, Adrian; Mazzola, Eugene P.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
[Ito, Yoichiro] NHLBI, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
EM adrian.weisz@fda.hhs.gov
NR 0
TC 0
Z9 0
U1 0
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 73-AGFD
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378300178
ER
PT J
AU White, JK
Hodoscek, M
Brooks, BR
Woodcock, HL
AF White, Justin K.
Hodoscek, Milan
Brooks, Bernard R.
Woodcock, H. Lee
TI Off-path simulations: A new chain-of-replica method to compute reaction
free energies
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [White, Justin K.; Woodcock, H. Lee] Univ S Florida, Dept Chem, Tampa, FL 33620 USA.
[Hodoscek, Milan] Natl Inst Chem, Ctr Mol Modeling, SI-1000 Ljubljana, Slovenia.
[Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA.
EM hlw@mail.usf.edu
NR 0
TC 0
Z9 0
U1 0
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 119-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378302047
ER
PT J
AU Yan, CQ
Schneider, JP
Pochan, DJ
AF Yan, Congqi
Schneider, Joel P.
Pochan, Darrin J.
TI Injectable solid hydrogels as cell carriers: Mechanism of b-hairpin
hydrogel shear thinning/immediate recovery and effects on cell payload
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Yan, Congqi; Pochan, Darrin J.] Univ Delaware, Dept Mat Sci & Engn, Newark, DE 19716 USA.
[Schneider, Joel P.] NCI, Ctr Canc Res, Frederick, MD 21702 USA.
EM cqyan@udel.edu
NR 0
TC 0
Z9 0
U1 0
U2 8
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 104-PMSE
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378306395
ER
PT J
AU Waidyanatha, S
Johnson, JD
Hong, SP
Godfrey-Robinson, VD
Graves, SW
Cristy, T
Dunnick, JK
Smith, CS
AF Waidyanatha, S.
Johnson, J. D.
Hong, S. P.
Godfrey-Robinson, V. D.
Graves, S. W.
Cristy, T.
Dunnick, J. K.
Smith, C. S.
TI Toxicokinetics of bis(2-chloroethoxy)methane following intravenous
administration and dermal application in male and female F344/N rats and
B6C3F1 mice
SO TOXICOLOGY LETTERS
LA English
DT Article
DE Bis(2-chloroethoxy)methane; Thiodiglycolic acid; Bioavailability;
Toxicokinetics; Metabolism
ID THIODIGLYCOLIC ACID; POLLUTANTS; HUMANS; CYCLOPHOSPHAMIDE; IFOSFAMIDE;
EXCRETION; METHANE; RIVER
AB In the National Toxicology Program's toxicity studies, rats were more sensitive than mice to Bis(2-chloroethoxy)methane (CEM) - induced cardiac toxicity following dermal application to male and female F344/N rats and B6C3F1 mice. Thiodiglycolic acid (TOGA) is a major metabolite of CEM in rats. It has been implicated that chemicals metabolized to TOGA cause cardiac toxicity in humans. Therefore, the toxicokinetics of CEM and TOGA were investigated in male and female F344/N rats and B6C3F1 mice following a single intravenous administration or dermal application of CEM to aid in the interpretation of the toxicity data. Absorption of CEM following dermal application was rapid in both species and genders. Bioavailability following dermal application was low but was higher in rats than in mice with females of both species showing higher bioavailability than males. CEM was rapidly distributed to the heart, thymus, and liver following both routes of administration. Plasma CEM C(max) and AUc(infinity) increased proportionally with dose, although at the dermal dose of 400 mg/kg in rats and 600 mg/kg in mice non-linear kinetics were apparent. Following dermal application, dose-normalized plasma CEM C(max) and AUC(infinity) was significantly higher in rats than in mice (p-value <0.0001 for all comparisons except for Cmax in the highest dose groups where p-value = 0.053). In rats, dose-normalized plasma CEM C(max) and AUC(infinity) was higher in females than in males: however, the difference was significant only at the lowest dose (p-value = 0.009 for C(max) and 0.056 for AUC(infinity)). Similar to rats, female mice also showed higher C(max) and AUC(infinity) in females than in male: the difference was significant only for C(max) at the lowest dose (p-value = 0.002). Dose-normalized heart CEM C(max) was higher in rats than in mice and in females than their male counterparts. The liver CEM C(max) was lower compared to that of heart and thymus in both rats and mice following intravenous administration and in rats following dermal application. This is likely due to the rapid metabolism of CEM in the liver as evidenced by the high concentration of TDGA measured in the liver. Dose-normalized plasma and heart TDGA C(max) values were higher in rats compared to mice. In rats, females had higher plasma and heart TDGA C. than males; however, there was no gender difference in plasma or heart TOGA C(max) in mice. These findings support the increased sensitivity of rats compared to mice to CEM-induced cardiac toxicity. Data also suggest that, either CEM C(max) or AUC can be used to predict the CEM-induced cardiac toxicity. Although, both plasma and heart TDGA C(max) was consistent with the observed species difference and the gender difference in rats, the gender difference in mice to cardiac toxicity could not be explained based on the TDGA data. This animal study suggests that toxicologically significant concentrations of CEM and TOGA could possibly be achieved in the systemic circulation and/or target tissues in humans as a result of dermal exposure to CEM. Published by Elsevier Ireland Ltd.
C1 [Waidyanatha, S.; Godfrey-Robinson, V. D.; Dunnick, J. K.; Smith, C. S.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Johnson, J. D.; Hong, S. P.; Graves, S. W.; Cristy, T.] Battelle Mem Inst, Columbus, OH 43201 USA.
RP Waidyanatha, S (reprint author), NIEHS, Natl Toxicol Program, 111 Alexander Dr,POB 12233,MD K2-07, Res Triangle Pk, NC 27709 USA.
EM waidyanathas@niehs.nih.gov
FU National Institute of Environmental Health Sciences (NIEHS), National
Institutes of Health, Department of Health and Human Services
[N01-ES-55551]
FX This study was conducted for the National Toxicology Program, National
Institute of Environmental Health Sciences (NIEHS), National Institutes
of Health, Department of Health and Human Services, under Contract No.
N01-ES-55551.
NR 22
TC 0
Z9 0
U1 1
U2 4
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0378-4274
J9 TOXICOL LETT
JI Toxicol. Lett.
PD AUG 28
PY 2011
VL 205
IS 2
BP 215
EP 226
DI 10.1016/j.toxlet.2011.06.012
PG 12
WC Toxicology
SC Toxicology
GA 809CO
UT WOS:000294029600016
PM 21708233
ER
PT J
AU Englund, EE
Neumann, S
Eliseeva, E
McCoy, J
Titus, S
Zheng, W
Southall, N
Marugan, J
Thomas, C
Austin, C
Gerhsngorn, M
Huang, WW
AF Englund, Erika E.
Neumann, Susanne
Eliseeva, Elena
McCoy, Josh
Titus, Steve
Zheng, Wei
Southall, Noel
Marugan, Juan
Thomas, Craig
Austin, Christopher
Gerhsngorn, Marvin
Huang, Wenwei
TI Synthesis and SAR analysis of a library of TSHR modulators
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 242nd National Meeting of the American-Chemical-Society (ACS)
CY AUG 28-SEP 01, 2011
CL Denver, CO
SP Amer Chem Soc (ACS)
C1 [Englund, Erika E.; McCoy, Josh; Titus, Steve; Zheng, Wei; Southall, Noel; Marugan, Juan; Thomas, Craig; Austin, Christopher; Huang, Wenwei] NIH, Chem Genom Ctr, Bethesda, MD 20892 USA.
[Neumann, Susanne; Eliseeva, Elena; Gerhsngorn, Marvin] NIDDK, Bethesda, MD 20892 USA.
RI Southall, Noel/H-8991-2012
OI Southall, Noel/0000-0003-4500-880X
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 28
PY 2011
VL 242
MA 374-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 880BE
UT WOS:000299378304687
ER
PT J
AU Bogoslovsky, T
Spatz, M
Chaudhry, A
Maric, D
Luby, M
Frank, J
Warach, S
AF Bogoslovsky, Tanya
Spatz, Maria
Chaudhry, Aneeka
Maric, Dragan
Luby, Marie
Frank, Joseph
Warach, Steven
TI Circulating CD133+CD34+progenitor cells inversely correlate with soluble
ICAM-1 in early ischemic stroke patients
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
ID ENDOTHELIAL PROGENITOR CELLS; INTERCELLULAR-ADHESION MOLECULE-1;
MATRIX-METALLOPROTEINASE EXPRESSION; ACUTE MYOCARDIAL-INFARCTION;
CARDIOEMBOLIC STROKE; BRAIN ISCHEMIA; RECRUITMENT; NEOVASCULARIZATION;
ANGIOGENESIS; MOBILIZATION
AB Background and Purpose: Both endothelial progenitor cells (EPC) and markers of neuroinflammation are candidate biomarkers for stroke severity and outcome prediction. A relationship between EPC and neuroinflammatory markers in early stroke is not fully elucidated. The objectives were to investigate correlations between EPC and neuroinflammation markers (adhesion molecules ICAM-1, VCAM-1, E-selectin, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, endothelin (ET)-1, markers of tissue injury (matrix metalloproteinases (MMP)-9 and tissue inhibitor of matrix metalloproteinases (TIMP)-1) in early stroke patients.
Methods: We prospectively recruited symptomatic patients with ischemic cerebrovascular disease. We assessed stroke severity by using of acute (diffusion-weighted imaging (DWI) and final lesion volumes (fluid attenuated inversion recovery (FLAIR). We measured serum soluble ICAM-1, VCAM-1, E-selectin, MMP-9, TIMP-1 and plasma TNF-alpha, IL-6, ET-1 by ELISA, and quantified EPC in mononuclear fraction of peripheral blood on days 1 and 3 in 17 patients (mean(SD) age 62(14), with admission National Institutes of Health Stroke Scale (NIHSS) 10(8)) selected from 175 patients with imaging confirmed ischemic stroke. Non-parametric statistics, univariate and multivariate analysis were used.
Results: Only ICAM-1 inversely correlated with EPC subset CD133+CD34+ on day 1 (Spearman r = -0.6, p < 0.01) and on day 3 (r = -0.967, p < 0.001). This correlation remained significant after adjustment for age and NIHSS (beta -0.992, p < 0.004), for glucose and systolic blood pressure (beta -0.86, p < 0.005), and for white blood cells and hematocrit (beta -1.057, p < 0.0001) on day 3. MMP-9 (r = 0.509, p < 0.04) and MMP-9/TIMP-1 (r = 0.59, p < 0.013) on day 1 correlated with acute lesion volume. Both IL-6 (r = 0.624, p < 0.01) and MMP-9/TIMP-1 (r = 0.56, p < 0.02) correlated with admission NIHSS.
Conclusion: Our study showed that high ICAM-1 is associated with low CD133+CD34+ subset of EPC. Biomarkers of neuroinflammation may predict tissue injury and stroke severity in early ischemia.
C1 [Bogoslovsky, Tanya; Luby, Marie; Warach, Steven] Natl Inst Neurol Disorders & Stroke, Stroke Diagnost & Therapeut Sect, NIH, Bethesda, MD 20892 USA.
[Spatz, Maria] Natl Inst Neurol Disorders & Stroke, Stroke Branch, NIH, Bethesda, MD 20892 USA.
[Maric, Dragan] Natl Inst Neurol Disorders & Stroke, NINDS Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA.
[Chaudhry, Aneeka; Frank, Joseph] Natl Inst Biomed Imaging & Bioengn, Frank Lab, Ctr Clin, NIH, Bethesda, MD 20892 USA.
RP Bogoslovsky, T (reprint author), Natl Inst Neurol Disorders & Stroke, Stroke Diagnost & Therapeut Sect, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM Tanya.Bogoslovsky.CTR@usuhs.mil
FU Division of Intramural Research of the National Institute of
Neurological Disorders and Stroke, National Institutes of Health; CNRM,
Uniformed Services University of Health Sciences
FX This research was supported by the Division of Intramural Research of
the National Institute of Neurological Disorders and Stroke, National
Institutes of Health and by CNRM, Uniformed Services University of
Health Sciences.
NR 34
TC 9
Z9 12
U1 0
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD AUG 26
PY 2011
VL 9
AR 145
DI 10.1186/1479-5876-9-145
PG 7
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 828QR
UT WOS:000295517800001
PM 21871109
ER
PT J
AU Plaza, L
Jimeno-Yepes, AJ
Diaz, A
Aronson, AR
AF Plaza, Laura
Jimeno-Yepes, Antonio J.
Diaz, Alberto
Aronson, Alan R.
TI Studying the correlation between different word sense disambiguation
methods and summarization effectiveness in biomedical texts
SO BMC BIOINFORMATICS
LA English
DT Article
ID DOMAIN; DOCUMENTS
AB Background: Word sense disambiguation (WSD) attempts to solve lexical ambiguities by identifying the correct meaning of a word based on its context. WSD has been demonstrated to be an important step in knowledge-based approaches to automatic summarization. However, the correlation between the accuracy of the WSD methods and the summarization performance has never been studied.
Results: We present three existing knowledge-based WSD approaches and a graph-based summarizer. Both the WSD approaches and the summarizer employ the Unified Medical Language System (UMLS) Metathesaurus as the knowledge source. We first evaluate WSD directly, by comparing the prediction of the WSD methods to two reference sets: the NLM WSD dataset and the MSH WSD collection. We next apply the different WSD methods as part of the summarizer, to map documents onto concepts in the UMLS Metathesaurus, and evaluate the summaries that are generated. The results obtained by the different methods in both evaluations are studied and compared.
Conclusions: It has been found that the use of WSD techniques has a positive impact on the results of our graph-based summarizer, and that, when both the WSD and summarization tasks are assessed over large and homogeneous evaluation collections, there exists a correlation between the overall results of the WSD and summarization tasks. Furthermore, the best WSD algorithm in the first task tends to be also the best one in the second. However, we also found that the improvement achieved by the summarizer is not directly correlated with the WSD performance. The most likely reason is that the errors in disambiguation are not equally important but depend on the relative salience of the different concepts in the document to be summarized.
C1 [Plaza, Laura; Diaz, Alberto] Univ Complutense Madrid, E-28040 Madrid, Spain.
[Jimeno-Yepes, Antonio J.; Aronson, Alan R.] Natl Lib Med, Bethesda, MD 20894 USA.
RP Plaza, L (reprint author), Univ Complutense Madrid, Calle Prof Jose Garcia Santesmases S-N, E-28040 Madrid, Spain.
EM lplazam@fdi.ucm.es
OI Diaz, Alberto/0000-0002-7641-8919; Jimeno Yepes, Antonio
Jose/0000-0002-6581-094X; DIAZ ESTEBAN, ALBERTO/0000-0003-1966-3421
FU Spanish Government; NIH, National Library of Medicine; National Library
of Medicine; [TIN2009-14659-C03-01]
FX This research was supported by the Spanish Government through the FPU
program and the project TIN2009-14659-C03-01.; This work was supported
in part by the Intramural Research Program of the NIH, National Library
of Medicine and by an appointment of A. Jimeno-Yepes to the NLM Research
Participation Program sponsored by the National Library of Medicine and
administered by the Oak Ridge Institute for Science and Education.
NR 46
TC 5
Z9 5
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD AUG 26
PY 2011
VL 12
AR 355
DI 10.1186/1471-2105-12-355
PG 13
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA 823SH
UT WOS:000295145000001
PM 21871110
ER
PT J
AU Alberobello, AT
Congedo, V
Liu, H
Cochran, C
Skarulis, MC
Forrest, D
Celi, FS
AF Alberobello, Anna Teresa
Congedo, Valentina
Liu, Hong
Cochran, Craig
Skarulis, Monica C.
Forrest, Douglas
Celi, Francesco S.
TI An intronic SNP in the thyroid hormone receptor beta gene is associated
with pituitary cell-specific over-expression of a mutant thyroid hormone
receptor beta 2 (R338W) in the index case of pituitary-selective
resistance to thyroid hormone
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
ID BINDING DOMAIN; MUTATION; IDENTIFICATION; SECRETION; KINDREDS; TSH; SEX
AB Background: The syndrome of resistance to thyroid hormone (RTH) is caused by mutations in the thyroid hormone receptor beta gene (THRB). The syndrome varies from asymptomatic to diffuse hypothyroidism, to pituitary-selective resistance with predominance of hyperthyroid signs and symptoms. The wide spectrum of clinical presentation is not completely attributable to specific THRB mutations. The THRB gene encodes two main isoforms, TR beta 1 which is widely distributed, and TR beta 2, whose expression is limited to the cochlea, retina, hypothalamus, and pituitary. Recent data demonstrated that in mice an intron enhancer region plays a critical role in the pituitary expression of the beta 2 isoform of the receptor. We thus hypothesized that polymorphisms in the human homologous region could modulate the pituitary expression of the mutated gene contributing to the clinical presentation of RTH.
Methods: Screening and in vitro characterization of polymorphisms of the intron enhancer region of the THRB gene in the index case of pituitary-selective RTH.
Results: The index case of pituitary-selective resistance is characterized by the missense R338W exon 9 mutation in cis with two common SNPs, rs2596623T and rs2596622C, located in the intron enhancer region of the THRB gene. Reporter gene assay experiments in GH3 pituitary-derived cells indicate that rs2596623T generates an increased pituitary cell-specific activity of the TR beta 2 promoter suggesting that rs2596623T leads to pituitary over-expression of the mutant allele.
Conclusions: The combined coding mutation and non-coding SNP therefore generate a tissue-specific dominant-negative condition recapitulating the patient's peculiar phenotype. This case illustrates the role of regulatory regions in modifying the clinical presentation of genetic diseases.
C1 [Alberobello, Anna Teresa; Congedo, Valentina; Cochran, Craig; Skarulis, Monica C.; Celi, Francesco S.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
[Congedo, Valentina] Univ G DAnnunzio, Dept Med & Sci Aging, Chieti, Italy.
[Liu, Hong; Forrest, Douglas] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD USA.
RP Celi, FS (reprint author), NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
EM fc93a@nih.gov
FU NIDDK [Z01-DK047057-01, DK 047037-04]
FX This research could have not been accomplished without the selfless
participation of the patients enrolled in the NIH RTH cohort. This work
was supported by the Intramural Research Program of the NIDDK, programs
Z01-DK047057-01, and DK 047037-04.
NR 24
TC 14
Z9 14
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD AUG 26
PY 2011
VL 9
AR 144
DI 10.1186/1479-5876-9-144
PG 7
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 819QN
UT WOS:000294844100001
PM 21871106
ER
PT J
AU Mashayekhi, M
Sandau, MM
Dunay, IR
Frickel, EM
Khan, A
Goldszmid, RS
Sher, A
Ploegh, HL
Murphy, TL
Sibley, LD
Murphy, KM
AF Mashayekhi, Mona
Sandau, Michelle M.
Dunay, Ildiko R.
Frickel, Eva M.
Khan, Asis
Goldszmid, Romina S.
Sher, Alan
Ploegh, Hidde L.
Murphy, Theresa L.
Sibley, L. David
Murphy, Kenneth M.
TI CD8 alpha(+) Dendritic Cells Are the Critical Source of Interleukin-12
that Controls Acute Infection by Toxoplasma gondii Tachyzoites
SO IMMUNITY
LA English
DT Article
ID CUTTING EDGE; IFN-GAMMA; INFLAMMATORY MONOCYTES; IL-12 PRODUCTION;
RESISTANCE; MICE; PARASITE; IMMUNITY; STIMULATION; NEUTROPHILS
AB CD8 alpha(+) dendritic cells (DCs) are important in vivo for cross-presentation of antigens derived from intracellular pathogens and tumors. Additionally, secretion of interleukin-12 (IL-12) by CD8 alpha(+) DCs suggests a role for these cells in response to Toxoplasma gondii antigens, although it remains unclear whether these cells are required for protection against T. gondii infection. Toward this goal, we examined T. gondii infection of Batf3(-/-) mice, which selectively lack only lymphoid-resident CD8 alpha(+) DCs and related peripheral CD103(+) DCs. Batf3(-/-) mice were extremely susceptible to T. gondii infection, with decreased production of IL-12 and interferon-gamma. IL-12 administration restored resistance in Batf3(-/-) mice, and mice in which IL-12 production was ablated only from CD8 alpha(+) DCs failed to control infection. These results reveal that the function of CD8 alpha(+) DCs extends beyond a role in cross-presentation and includes a critical role for activation of innate immunity through IL-12 production during T. gondii infection.
C1 [Mashayekhi, Mona; Sandau, Michelle M.; Murphy, Theresa L.; Murphy, Kenneth M.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
[Dunay, Ildiko R.; Khan, Asis; Sibley, L. David] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.
[Murphy, Kenneth M.] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA.
[Frickel, Eva M.; Ploegh, Hidde L.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
[Goldszmid, Romina S.; Sher, Alan] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Goldszmid, Romina S.] NCI, Expt Immunol Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.
RP Murphy, KM (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
EM kmurphy@pathology.wustl.edu
FU Howard Hughes Medical Institute; American Heart Association; [AI059176]
FX This work was supported by the Howard Hughes Medical Institute (K.M.M.),
the American Heart Association Midwest Affiliate Predoctoral Fellowship
Program (M.M.), and AI059176 (L.D.S.).
NR 31
TC 126
Z9 129
U1 0
U2 12
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD AUG 26
PY 2011
VL 35
IS 2
BP 249
EP 259
DI 10.1016/j.immuni.2011.08.008
PG 11
WC Immunology
SC Immunology
GA 813SC
UT WOS:000294387900014
PM 21867928
ER
PT J
AU Wei, G
Abraham, BJ
Yagi, R
Jothi, R
Cui, KR
Sharma, S
Narlikar, L
Northrup, DL
Tang, QS
Paul, WE
Zhu, JF
Zhao, KJ
AF Wei, Gang
Abraham, Brian J.
Yagi, Ryoji
Jothi, Raja
Cui, Kairong
Sharma, Suveena
Narlikar, Leelavati
Northrup, Daniel L.
Tang, Qingsong
Paul, William E.
Zhu, Jinfang
Zhao, Keji
TI Genome-wide Analyses of Transcription Factor GATA3-Mediated Gene
Regulation in Distinct T Cell Types
SO IMMUNITY
LA English
DT Article
ID FACTOR GATA-3; CHROMATIN OCCUPANCY; LINEAGE COMMITMENT; DNA-BINDING;
EXPRESSION; DIFFERENTIATION; CD4; FINGER; TH1; IDENTIFICATION
AB The transcription factor GATA3 plays an essential role during T cell development and T helper 2 (Th2) cell differentiation. To understand GATA3-mediated gene regulation, we identified genome-wide GATA3 binding sites in ten well-defined developmental and effector T lymphocyte lineages. In the thymus, GATA3 directly regulated many critical factors, including Th-POK, Notch1, and T cell receptor subunits. In the periphery, GATA3 induced a large number of Th2 cell-specific as well as Th2 cell-nonspecific genes, including several transcription factors. Our data also indicate that GATA3 regulates both active and repressive histone modifications of many target genes at their regulatory elements near GATA3 binding sites. Overall, although GATA3 binding exhibited both shared and cell-specific patterns among various T cell lineages, many genes were either positively or negatively regulated by GATA3 in a cell type-specific manner, suggesting that GATA3-mediated gene regulation depends strongly on cofactors existing in different T cells.
C1 [Yagi, Ryoji; Sharma, Suveena; Paul, William E.; Zhu, Jinfang] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Wei, Gang; Abraham, Brian J.; Cui, Kairong; Northrup, Daniel L.; Tang, Qingsong; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Jothi, Raja; Narlikar, Leelavati] Natl Inst Environm Hlth Sci, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA.
RP Zhu, JF (reprint author), NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
EM jfzhu@niaid.nih.gov; zhaok@nhlbi.nih.gov
RI Zhu, Jinfang/B-7574-2012; cheng, yong/I-4270-2012; Jothi,
Raja/G-3780-2015
FU Division of Intramural Research, National Institute of Environmental
Health Sciences [Z01ES102625]; Division of Intramural Research, National
Institute of Allergy and Infectious Diseases; Division of Intramural
Research, National Heart, Lung and Blood Institute, National Institutes
of Health, USA
FX We thank W. Leonard for critical reading of the manuscript. We thank I.
Chepelev, G. Hu, and D. Schones for helpful discussions on data
analysis. This work was supported by the Division of Intramural
Research, National Institute of Environmental Health Sciences (R.J.;
Project Number Z01ES102625), Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, and Division of Intramural
Research, National Heart, Lung and Blood Institute, National Institutes
of Health, USA.
NR 43
TC 124
Z9 127
U1 0
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD AUG 26
PY 2011
VL 35
IS 2
BP 299
EP 311
DI 10.1016/j.immuni.2011.08.007
PG 13
WC Immunology
SC Immunology
GA 813SC
UT WOS:000294387900018
PM 21867929
ER
PT J
AU Vojnov, L
Martins, MA
Almeida, JR
Ende, Z
Rakasz, EG
Reynolds, MR
Leon, EJ
Weisgrau, KL
Burwitz, BJ
Folkvord, JM
de Santana, MGV
Neves, PCC
Connick, E
Skinner, PJ
Gostick, E
O'Connor, DH
Wilson, NA
Bonaldo, MC
Galler, R
Price, DA
Douek, DC
Watkins, DI
AF Vojnov, Lara
Martins, Mauricio A.
Almeida, Jorge R.
Ende, Zachary
Rakasz, Eva G.
Reynolds, Matthew R.
Leon, Enrique J.
Weisgrau, Kim L.
Burwitz, Benjamin J.
Folkvord, Joy M.
Veloso de Santana, Marlon G.
Costa Neves, Patricia C.
Connick, Elizabeth
Skinner, Pamela J.
Gostick, Emma
O'Connor, David H.
Wilson, Nancy A.
Bonaldo, Myrna C.
Galler, Ricardo
Price, David A.
Douek, Danny C.
Watkins, David I.
TI GagCM9-Specific CD8(+) T Cells Expressing Limited Public TCR Clonotypes
Do Not Suppress SIV Replication In Vivo
SO PLOS ONE
LA English
DT Article
ID SIMIAN-IMMUNODEFICIENCY-VIRUS; CELLULAR IMMUNE-RESPONSES;
RHESUS-MONKEYS; LYMPHOCYTE RESPONSE; HIV-1 INFECTION;
MAMU-B-ASTERISK-08-POSITIVE MACAQUES; GASTROINTESTINAL-TRACT; SIVMAC239
REPLICATION; VIRAL REPLICATION; ESCAPE MUTATIONS
AB Several lines of evidence suggest that HIV/SIV-specific CD8(+) T cells play a critical role in the control of viral replication. Recently we observed high levels of viremia in Indian rhesus macaques vaccinated with a segment of SIVmac239 Gag (Gag(45-269)) that were subsequently infected with SIVsmE660. These seven Mamu-A*01(+) animals developed CD8(+) T cell responses against an immunodominant epitope in Gag, GagCM9, yet failed to control virus replication. We carried out a series of immunological and virological assays to understand why these Gag-specific CD8(+) T cells could not control virus replication in vivo. GagCM9-specific CD8(+) T cells from all of the animals were multifunctional and were found in the colonic mucosa. Additionally, GagCM9-specific CD8(+) T cells accessed B cell follicles, the primary residence of SIV-infected cells in lymph nodes, with effector to target ratios between 20-250 GagCM9-specific CD8(+) T cells per SIV-producing cell. Interestingly, vaccinated animals had few public TCR clonotypes within the GagCM9-specific CD8(+) T cell population pre- and post-infection. The number of public TCR clonotypes expressed by GagCM9-specific CD8(+) T cells post-infection significantly inversely correlated with chronic phase viral load. It is possible that these seven animals failed to control viral replication because of the narrow TCR repertoire expressed by the GagCM9-specific CD8(+) T cell population elicited by vaccination and infection.
C1 [Vojnov, Lara; Martins, Mauricio A.; Rakasz, Eva G.; Reynolds, Matthew R.; Burwitz, Benjamin J.; O'Connor, David H.; Wilson, Nancy A.; Watkins, David I.] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53706 USA.
[Almeida, Jorge R.; Ende, Zachary; Douek, Danny C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Rakasz, Eva G.; Leon, Enrique J.; Weisgrau, Kim L.; Watkins, David I.] Wisconsin Natl Primate Res Ctr, Madison, WI USA.
[Folkvord, Joy M.; Connick, Elizabeth] Univ Colorado, Sch Med, Denver, CO USA.
[Veloso de Santana, Marlon G.; Costa Neves, Patricia C.; Bonaldo, Myrna C.] Inst Oswaldo Cruz FIOCRUZ, Lab Biol Mol Flavivirus, Rio De Janeiro, Brazil.
[Skinner, Pamela J.] Univ Minnesota, Dept Vet & Biomed Sci, St Paul, MN 55108 USA.
[Galler, Ricardo] Fundacao Oswaldo Cruz, Inst Tecnol Imunobiol, Rio De Janeiro, Brazil.
[Gostick, Emma; Price, David A.] Cardiff Univ, Dept Infect Immun & Biochem, Cardiff, S Glam, Wales.
RP Vojnov, L (reprint author), Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53706 USA.
EM Watkins@primate.wisc.edu
RI Bonaldo, Myrna/D-9494-2013; Vacinas, Inct/J-9431-2013; Galler,
Ricardo/B-3280-2014; Price, David/C-7876-2013;
OI Price, David/0000-0001-9416-2737; Ramos de Almeida,
Jorge/0000-0002-5009-8478; Martins, Mauricio/0000-0001-8336-216X;
o'connor, david/0000-0003-2139-470X
FU National Institutes of Health (NIH)/National Institute of Allergy and
Infectious Disease [R01 AI076114, R01 AI049120, R24 RR015371, R24
RR016038]; National Center for Research Resources (NCRR) [R51 RR000167]
FX This research was supported by National Institutes of Health
(NIH)/National Institute of Allergy and Infectious Disease grants R01
AI076114, R01 AI049120, R24 RR015371, and R24 RR016038 and in part by
grant R51 RR000167 from the National Center for Research Resources
(NCRR) awarded to the WNPRC, University of Wisconsin-Madison. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 60
TC 8
Z9 8
U1 1
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 26
PY 2011
VL 6
IS 8
AR e23515
DI 10.1371/journal.pone.0023515
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 812MY
UT WOS:000294298800011
PM 21887264
ER
PT J
AU Shchedrina, VA
Kabil, H
Vorbruggen, G
Lee, BC
Turanov, AA
Hirosawa-Takamori, M
Kim, HY
Harshman, LG
Hatfield, DL
Gladyshev, VN
AF Shchedrina, Valentina A.
Kabil, Hadise
Vorbruggen, Gerd
Lee, Byung Cheon
Turanov, Anton A.
Hirosawa-Takamori, Mitsuko
Kim, Hwa-Young
Harshman, Lawrence G.
Hatfield, Dolph L.
Gladyshev, Vadim N.
TI Analyses of Fruit Flies That Do Not Express Selenoproteins or Express
the Mouse Selenoprotein, Methionine Sulfoxide Reductase B1, Reveal a
Role of Selenoproteins in Stress Resistance
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID LIFE-SPAN; DROSOPHILA-MELANOGASTER; OXIDATIVE DAMAGE; SELENOPHOSPHATE
SYNTHETASE; SELENOCYSTEINE INCORPORATION; ANTIOXIDANT DEFENSE;
BINDING-PROTEIN; GENE; LONGEVITY; OVEREXPRESSION
AB Selenoproteins are essential in vertebrates because of their crucial role in cellular redox homeostasis, but some invertebrates that lack selenoproteins have recently been identified. Genetic disruption of selenoprotein biosynthesis had no effect on lifespan and oxidative stress resistance of Drosophila melanogaster. In the current study, fruit flies with knock-out of the selenocysteine-specific elongation factor were metabolically labeled with Se-75; they did not incorporate selenium into proteins and had the same lifespan on a chemically defined diet with or without selenium supplementation. These flies were, however, more susceptible to starvation than controls, and this effect could be ascribed to the function of selenoprotein K. We further expressed mouse methionine sulfoxide reductase B1 (MsrB1), a selenoenzyme that catalyzes the reduction of oxidized methionine residues and has protein repair function, in the whole body or the nervous system of fruit flies. This exogenous selenoprotein could only be expressed when the Drosophila selenocysteine insertion sequence element was used, whereas the corresponding mouse element did not support selenoprotein synthesis. Ectopic expression of MsrB1 in the nervous system led to an increase in the resistance against oxidative stress and starvation, but did not affect lifespan and reproduction, whereas ubiquitous MsrB1 expression had no effect. Dietary selenium did not influence lifespan of MsrB1-expressing flies. Thus, in contrast to vertebrates, fruit flies preserve only three selenoproteins, which are not essential and play a role only under certain stress conditions, thereby limiting the use of the micronutrient selenium by these organisms.
C1 [Shchedrina, Valentina A.; Lee, Byung Cheon; Turanov, Anton A.; Gladyshev, Vadim N.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA.
[Shchedrina, Valentina A.; Lee, Byung Cheon; Turanov, Anton A.; Gladyshev, Vadim N.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Kabil, Hadise; Harshman, Lawrence G.] Univ Nebraska, Sch Biol Sci, Lincoln, NE 68588 USA.
[Vorbruggen, Gerd; Hirosawa-Takamori, Mitsuko] Max Planck Inst Biophys Chem, Abt Mol Entwicklungsbiol, D-37077 Gottingen, Germany.
[Kim, Hwa-Young] Yeungnam Univ, Coll Med, Dept Biochem & Mol Biol, Taegu 705717, South Korea.
[Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Gladyshev, VN (reprint author), New Res Bldg,77 Ave Louis Pasteur,Rm 435, Boston, MA 02115 USA.
EM vgladyshev@rics.bwh.harvard.edu
RI Gladyshev, Vadim/A-9894-2013
FU National Institutes of Health [AG021518, GM061603, DK074136]; Center for
Cancer Research, NCI; National Research Foundation of Korea
[2010-0001240]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants AG021518, GM061603 (to V. N. G.), and DK074136 (to L. G.
H.), the Intramural Research Program at the Center for Cancer Research,
NCI (to D. L. H.), and National Research Foundation of Korea Grant
2010-0001240 (to H. Y. K.).
NR 59
TC 12
Z9 13
U1 0
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 26
PY 2011
VL 286
IS 34
BP 29449
EP 29461
DI 10.1074/jbc.M111.257600
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 809IU
UT WOS:000294046600002
PM 21622567
ER
PT J
AU Zhang, YX
Bonzo, JA
Gonzalez, FJ
Wang, L
AF Zhang, Yuxia
Bonzo, Jessica A.
Gonzalez, Frank J.
Wang, Li
TI Diurnal Regulation of the Early Growth Response 1 (Egr-1) Protein
Expression by Hepatocyte Nuclear Factor 4 alpha (HNF4 alpha) and Small
Heterodimer Partner (SHP) Cross-talk in Liver Fibrosis
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID BILE-ACID BIOSYNTHESIS; RECEPTOR-SHP; GENE-EXPRESSION; TARGET GENES;
INJURY; CELLS; IDENTIFICATION; STIMULATION; FIBROBLASTS; METABOLISM
AB Early growth response 1 (Egr-1) protein is a critical regulator of genes contributing to liver fibrosis; however, little is known about the upstream transcriptional factors that control its expression. Here we show that Egr-1 expression is tightly regulated by nuclear receptor signaling. Hepatocyte nuclear factor 4 alpha (HNF4 alpha) activated the Egr-1 promoter through three DR1 response elements as identified by trans-activation assays. Deletion of these response elements or knockdown of HNF4 alpha using siRNA largely abrogated Egr-1 promoter activation. HNF4 alpha activity, as well as its enrichment on the Egr-1 promoter, were markedly repressed by small heterodimer partner (SHP) co-expression. Egr-1 mRNA and protein were transiently induced by HNF4 alpha. On the contrary, HNF4 alpha siRNA reduced Egr-1 expression at both the mRNA and protein levels, and overexpression of SHP reversed these effects. Conversely, knockdown of SHP by siRNA elevated Egr-1 protein. Interestingly, Egr-1 mRNA exhibited diurnal fluctuation, which was synchronized to the cyclic expression of SHP and HNF4 alpha after cells were released from serum shock. Unexpectedly, the levels of Egr-1 mRNA and protein were highly up-regulated in Hnf4 alpha(-/-) mice. Both HNF4 alpha and Egr-1 expression were dramatically increased in SHP-/- mice with bile duct ligation and in human cirrhotic livers, which was inversely correlated with diminished SHP expression. In conclusion, our study revealed control network for Egr-1 expression through a feedback loop between SHP and HNF4 alpha.
C1 [Zhang, Yuxia; Wang, Li] Univ Utah, Sch Med, Huntsman Canc Inst, Dept Med, Salt Lake City, UT 84132 USA.
[Zhang, Yuxia; Wang, Li] Univ Utah, Sch Med, Huntsman Canc Inst, Dept Oncol Sci, Salt Lake City, UT 84132 USA.
[Bonzo, Jessica A.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Wang, L (reprint author), 30 North 1900 East,SOM 3C310, Salt Lake City, UT 84132 USA.
EM l.wang@hsc.utah.edu
FU National Institutes of Health [DK080440,
N01-DK-7-0004/HHSN267200700004C]; Multidisciplinary Cancer Research
Training Program [T32CA092347]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant DK080440 (to L. W.).; Supported by Multidisciplinary Cancer
Research Training Program Grant T32CA092347.; We thank Dr. Scott
Friedman for the LX2 cells and Drs. Frances Sladek and Akiyoshi Fukamizu
for the HNF4 alpha constructs. Normal human liver and cirrhotic liver
specimens were obtained through the Liver Tissue Cell Distribution
System (Minneapolis, MN), which is funded by National Institutes of
Health Contract N01-DK-7-0004/HHSN267200700004C.
NR 40
TC 16
Z9 18
U1 0
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 26
PY 2011
VL 286
IS 34
BP 29635
EP 29643
DI 10.1074/jbc.M111.253039
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 809IU
UT WOS:000294046600022
PM 21725089
ER
PT J
AU Chung, YW
Kim, HK
Kim, IY
Yim, MB
Chock, PB
AF Chung, Youn Wook
Kim, Ha Kun
Kim, Ick Young
Yim, Moon B.
Chock, P. Boon
TI Dual Function of Protein Kinase C (PKC) in
12-O-Tetradecanoylphorbol-13-acetate (TPA)-induced Manganese Superoxide
Dismutase (MnSOD) Expression ACTIVATION OF CREB AND FOXO3a BY PKC-alpha
PHOSPHORYLATION AND BY PKC-MEDIATED INACTIVATION OF Akt, RESPECTIVELY
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; FORKHEAD TRANSCRIPTION FACTOR;
GENE-EXPRESSION; SIGNAL-TRANSDUCTION; OXIDATIVE STRESS; PROMOTER REVEAL;
PHORBOL ESTER; CANCER-CELLS; FACTOR-ALPHA
AB 12-O-tetradecanoylphorbol-13-acetate (TPA) has been shown to induce transcriptional activation of human manganese superoxide dismutase (MnSOD) mRNA in human lung carcinoma cells, A549, mediated by a protein kinase C (PKC)-dependent activation of cAMP-responsive element-binding protein (CREB)-1/ATF-1-like factors. In this study, we showed that MnSOD protein expression was elevated in response to TPA or TNF-alpha, but not to hydrogen peroxide treatment. TPA-induced generation of reactive oxygen species (ROS) was blocked by pretreatment of the PKC inhibitor BIM and NADPH oxidase inhibitor DPI. Small interfering RNA (siRNA) experiments indicated that knocking down the NADPH oxidase components e.g. Rac1, p22(phox), p67(phox), and NOXO1 in A549 cells impaired TPA-induced MnSOD expression. To identify the PKC isozyme involved, we used a sod2 gene response reporter plasmid, pSODLUC-3340-I2E-C, capable of sensing the effect of TNF-alpha and TPA, to monitor the effects of PKC isozyme-specific inhibitors and siRNA-induced knockdown of specific PKC isozyme. Our data indicate that TPA-induced MnSOD expression was independent of p53 and most likely mediated by PKC-alpha-, and -epsilon-dependent signaling pathways. Furthermore, siRNA-induced knock-down of CREB and Forkhead box class O (FOXO) 3a led to a reduction in TPA-induced MnSOD gene expression. Together, our results revealed that TPA up-regulates, in part, two PKC-dependent transcriptional pathways to induce MnSOD expression. One pathway involves PKC-alpha catalyzed phosphorylation of CREB and the other involves a PKC-mediated the PP2A catalyzed dephosphorylation of Akt at Ser(473) which in turn leads to FOXO3a Ser(253) dephosphorylation and its activation.
C1 [Chung, Youn Wook; Kim, Ha Kun; Yim, Moon B.; Chock, P. Boon] NHLBI, Biochim Lab, NIH, Bethesda, MD 20892 USA.
[Kim, Ick Young] Korea Univ, Sch Life Sci & Biotechnol, Lab Cellular & Mol Biochem, Seoul 136701, South Korea.
RP Yim, MB (reprint author), NHLBI, Biochim Lab, NIH, Bldg 50,Room 2134,MSC 8012, Bethesda, MD 20892 USA.
EM bchock@nih.gov
FU NHLBI, National Institutes of Health
FX This work was supported, in whole or in part, by the Intramural Research
Program of NHLBI, National Institutes of Health.
NR 55
TC 22
Z9 23
U1 0
U2 8
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 26
PY 2011
VL 286
IS 34
BP 29681
EP 29690
DI 10.1074/jbc.M111.264945
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 809IU
UT WOS:000294046600027
PM 21705328
ER
PT J
AU White, CD
Li, ZG
Dillon, DA
Sacks, DB
AF White, Colin D.
Li, Zhigang
Dillon, Deborah A.
Sacks, David B.
TI IQGAP1 Protein Binds Human Epidermal Growth Factor Receptor 2 (HER2) and
Modulates Trastuzumab Resistance
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID BREAST-CANCER CELLS; DEPENDENT KINASE INHIBITOR; ERBB RECEPTORS;
METASTATIC BREAST; SYNERGISTICALLY INHIBIT; MONOCLONAL-ANTIBODY;
SIGNALING PATHWAYS; SCAFFOLD PROTEINS; NEU ONCOGENE; PROLIFERATION
AB Human epidermal growth factor receptor 2 (HER2) is overexpressed in 20-25% of breast cancers. Increased HER2 expression is an adverse prognostic factor and correlates with decreased patient survival. HER2-positive (HER2(+)) breast cancer is treated with trastuzumab. Unfortunately, some patients are intrinsically refractory to therapy, and many who do respond initially become resistant within 1 year. Understanding the molecular mechanisms underlying HER2 signaling and trastuzumab resistance is essential to reduce breast cancer mortality. IQGAP1 is a ubiquitously expressed scaffold protein that contains multiple protein interaction domains. By regulating its binding partners IQGAP1 integrates signaling pathways, several of which contribute to breast tumorigenesis. We show here that IQGAP1 is overexpressed in HER2(+) breast cancer tissue and binds directly to HER2. Knockdown of IQGAP1 decreases HER2 expression, phosphorylation, signaling, and HER2-stimulated cell proliferation, effects that are all reversed by reconstituting cells with IQGAP1. Reducing IQGAP1 up-regulates p27, and blocking this increase attenuates the growth inhibitory effects of IQGAP1 knockdown. Importantly, IQGAP1 is overexpressed in trastuzumab-resistant breast epithelial cells, and reducing IQGAP1 both augments the inhibitory effects of trastuzumab and restores trastuzumab sensitivity to trastuzumab-resistant SkBR3 cells. These data suggest that inhibiting IQGAP1 function may represent a rational strategy for treating HER2(+) breast carcinoma.
C1 [White, Colin D.] Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.
[White, Colin D.; Li, Zhigang; Dillon, Deborah A.; Sacks, David B.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[White, Colin D.; Li, Zhigang; Dillon, Deborah A.; Sacks, David B.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Li, Zhigang; Sacks, David B.] NIH, Bethesda, MD 20892 USA.
RP White, CD (reprint author), Beth Israel Deaconess Med Ctr, 3 Blackfan Circle, Boston, MA 02115 USA.
EM cdwhite@bidmc.harvard.edu
OI Sacks, David/0000-0003-3100-0735
FU National Institutes of Health [R01CA075205-09]; Department of Defense
[BC087504]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant R01CA075205-09 (to D. B. S.). This work was also funded by
the Department of Defense Breast Cancer Research Program (BC087504; to
C. D. W.).
NR 70
TC 19
Z9 19
U1 0
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 26
PY 2011
VL 286
IS 34
BP 29734
EP 29747
DI 10.1074/jbc.M111.220939
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 809IU
UT WOS:000294046600033
PM 21724847
ER
PT J
AU Joshi, A
Garg, H
Ablan, SD
Freed, EO
AF Joshi, Anjali
Garg, Himanshu
Ablan, Sherimay D.
Freed, Eric O.
TI Evidence of a Role for Soluble N-Ethylmaleimide-sensitive Factor
Attachment Protein Receptor (SNARE) Machinery in HIV-1 Assembly and
Release
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; INFECTIOUS-ANEMIA VIRUS;
GAG-MEMBRANE-BINDING; PLASMA-MEMBRANE; INTRACELLULAR TRAFFICKING;
CELL-SURFACE; PARTICLE-PRODUCTION; PRIMARY MACROPHAGES; FUSION PROTEIN;
MATRIX DOMAIN
AB Retrovirus assembly is a complex process that requires the orchestrated participation of viral components and host-cell factors. The concerted movement of different viral proteins to specific sites in the plasma membrane allows for virus particle assembly and ultimately budding and maturation of infectious virions. The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins constitute the minimal machinery that catalyzes the fusion of intracellular vesicles with the plasma membrane, thus regulating protein trafficking. Using siRNA and dominant negative approaches we demonstrate here that generalized disruption of the host SNARE machinery results in a significant reduction in human immunodeficiency virus type 1 (HIV-1) and equine infectious anemia virus particle production. Further analysis of the mechanism involved revealed a defect at the level of HIV-1 Gag localization to the plasma membrane. Our findings demonstrate for the first time a role of SNARE proteins in HIV-1 assembly and release, likely by affecting cellular trafficking pathways required for Gag transport and association with the plasma membrane.
C1 [Joshi, Anjali; Garg, Himanshu] Texas Tech Univ, Hlth Sci Ctr, Dept Biomed Sci, Ctr Excellence Infect Dis, El Paso, TX 79905 USA.
[Joshi, Anjali; Garg, Himanshu] Texas Tech Univ, Hlth Sci Ctr, Paul L Foster Sch Med, Dept Pediat, El Paso, TX 79905 USA.
[Ablan, Sherimay D.; Freed, Eric O.] NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, NIH, Frederick, MD 21702 USA.
RP Joshi, A (reprint author), 5001 El Paso Dr,MSB-1, El Paso, TX 79905 USA.
EM anjali.joshi@ttuhsc.edu
FU Center for Cancer Research, NCI, National Institutes of Health;
Intramural AIDS Targeted Antiviral Program
FX This work was supported by the Intramural Research Program of the Center
for Cancer Research, NCI, National Institutes of Health. This work was
also supported by the Intramural AIDS Targeted Antiviral Program.
NR 86
TC 13
Z9 14
U1 0
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 26
PY 2011
VL 286
IS 34
BP 29861
EP 29871
DI 10.1074/jbc.M111.241521
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 809IU
UT WOS:000294046600045
PM 21680744
ER
PT J
AU Fukushima, M
Villar, J
Tsai-Morris, CH
Dufau, ML
AF Fukushima, Masato
Villar, Joaquin
Tsai-Morris, Chon-Hwa
Dufau, Maria L.
TI Gonadotropin-regulated Testicular RNA Helicase (GRTH/DDX25), a Negative
Regulator of Luteinizing/Chorionic Gonadotropin Hormone-induced
Steroidogenesis in Leydig Cells CENTRAL ROLE OF STEROIDOGENIC ACUTE
REGULATORY PROTEIN (StAR)
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID MEDIATED STEROIDOGENESIS; RAT TESTIS; SPERMATOGENESIS; GENE;
CHOLESTEROL; TRANSLATION; MODULATION
AB Gonadotropin-regulated testicular RNA helicase (GRTH/DDX25) is a testis-specific gonadotropin-regulated RNA helicase that is present in Leydig cells (LCs) and germ cells and is essential for spermatid development and completion of spermatogenesis. Normal basal levels of testosterone in serum and LCs were observed in GRTH null (GRTH(-/-)) mice. However, testosterone production was enhanced in LCs of GRTH(-/-) mice compared with WT mice by both in vivo and in vitro human chorionic gonadotropin stimulation. LCs of GRTH(-/-) mice had swollen mitochondria with a significantly increased cholesterol content in the inner mitochondrial membrane. Basal protein levels of SREBP2, HMG-CoAreductase, and steroidogenic acute regulatory protein (StAR; a protein that transports cholesterol to the inner mitochondrial membrane) were markedly increased in LCs of GRTH(-/-) mice compared with WT mice. Gonadotropin stimulation caused an increase in StAR mRNA levels and protein expression inGRTH(-/-) mice versus WT mice, with no further increase in SREBP2 and down-regulation of HMG-CoA reductase protein. The half-life of StAR mRNA was significantly increased in GRTH(-/-) mice. Moreover, association of StAR mRNA with GRTH protein was observed in WT mice. Human chorionic gonadotropin increased GRTH gene expression and its associated StAR protein at cytoplasmic sites. Taken together, these findings indicate that, through its negative role in StAR message stability, GRTH regulates cholesterol availability at the mitochondrial level. The finding of an inhibitory action of GRTH associated with gonadotropin-mediated steroidogenesis has provided insights into a novel negative autocrine molecular control mechanism of this helicase in the regulation of steroid production in the male.
C1 [Fukushima, Masato; Villar, Joaquin; Tsai-Morris, Chon-Hwa; Dufau, Maria L.] Eunice Kennedy Shriver NICHD, Sect Mol Endocrinol, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
RP Dufau, ML (reprint author), Eunice Kennedy Shriver NICHD, Sect Mol Endocrinol, Program Dev Endocrinol & Genet, NIH, Bldg 49,Rm 6A-36, Bethesda, MD 20892 USA.
EM dufaum@mail.nih.gov
FU NICHD, National Institutes of Health
FX This work was supported by the NICHD Intramural Research Program,
National Institutes of Health.
NR 23
TC 8
Z9 8
U1 0
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 26
PY 2011
VL 286
IS 34
BP 29932
EP 29940
DI 10.1074/jbc.M111.236083
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 809IU
UT WOS:000294046600052
PM 21719703
ER
PT J
AU Merikangas, KR
Cui, LH
Richardson, AK
Isler, H
Khoromi, S
Nakamura, E
Lamers, F
Rossler, W
Ajdacic-Gross, V
Gamma, A
Angst, J
AF Merikangas, Kathleen R.
Cui, Lihong
Richardson, Amanda Kalaydjian
Isler, Hansruedi
Khoromi, Suzan
Nakamura, Erin
Lamers, Femke
Roessler, Wulf
Ajdacic-Gross, Vladeta
Gamma, Alex
Angst, Jules
TI Magnitude, impact, and stability of primary headache subtypes: 30 year
prospective Swiss cohort study
SO BRITISH MEDICAL JOURNAL
LA English
DT Article
ID TENSION-TYPE HEADACHE; POPULATION-BASED TWIN; FOLLOW-UP; YOUNG-ADULTS;
ZURICH COHORT; MIGRAINE HEADACHES; MENTAL-DISORDERS; UNITED-STATES;
PREVALENCE; EPIDEMIOLOGY
AB Objective To determine the prevalence, impact, and stability of different subtypes of headache in a 30 year prospective follow-up study of a general population sample.
Design Prospective cohort study.
Setting Canton of Zurich, Switzerland.
Participants 591 people aged 19-20 from a cohort of 4547 residents of Zurich, Switzerland, interviewed seven times across 30 years of follow-up.
Main outcome measures Prevalence of headache; stability of the predominant subtype of headache over time; and age of onset, severity, impact, family history, use of healthcare services, and drugs for headache subtypes.
Results The average one year prevalences of subtypes of headache were 0.9% (female: male ratio of 2.8) for migraine with aura, 10.9% (female: male ratio of 2.2) for migraine without aura, and 11.5% (female: male ratio of 1.2) for tension-type headache. Cumulative 30 year prevalences of headache subtypes were 3.0% for migraine with aura, 36.0% for migraine without aura, and 29.3% for tension-type headache. Despite the high prevalence of migraine without aura, most cases were transient and only about 20% continued to have migraine for more than half of the follow-up period. 69% of participants with migraine and 58% of those with tension-type headache manifested the same predominant subtype over time. However, the prospective stability of the predominant headache subtypes was quite low, with substantial crossover among the subtypes and no specific ordinal pattern of progression. A gradient of severity of clinical correlates and service use was present across headache subtypes; the greatest effect was for migraine with aura followed by migraine without aura, and then tension-type headache and unclassified headaches.
Conclusions These findings highlight the importance of prospective follow-up of people with headache. The substantial longitudinal overlap among subtypes of headache shows the developmental heterogeneity of headache syndromes. Studies of the causes of headache that apply diagnostic nomenclature based on distinctions between discrete headache subtypes may not capture the true nature of headache in the general population.
C1 [Merikangas, Kathleen R.; Cui, Lihong; Richardson, Amanda Kalaydjian; Khoromi, Suzan; Nakamura, Erin; Lamers, Femke] NIMH, NIH, Intramural Res Program, Genet Epidemiol Res Branch, Bethesda, MD 20892 USA.
[Isler, Hansruedi] Hochhaus Schanze, CH-8032 Zurich, Switzerland.
[Roessler, Wulf; Ajdacic-Gross, Vladeta; Gamma, Alex; Angst, Jules] Univ Zurich, Hosp Psychiat, Zurich, Switzerland.
RP Merikangas, KR (reprint author), NIMH, NIH, Intramural Res Program, Genet Epidemiol Res Branch, Bethesda, MD 20892 USA.
EM Kathleen.Merikangas@nih.gov
RI Lamers, Femke/G-5161-2012;
OI Ajdacic-Gross, Vladeta/0000-0002-7032-9237
FU Swiss National Science Foundation [3200-050881.97/1]; National Institute
of Mental Health [ZIAMH002807-07]; Netherlands Organisation for
Scientific Research (NWO)
FX This work was supported by grant 3200-050881.97/1 of the Swiss National
Science Foundation and National Institute of Mental Health, Intramural
Research Program grant No ZIAMH002807-07 for collaborative analyses of
the Zurich Cohort Study. FL is supported by a Rubicon fellowship from
the Netherlands Organisation for Scientific Research (NWO). The views
and opinions expressed in this report are those of the authors and
should not be construed to represent the views of any of the sponsoring
organisations, agencies, or US government.
NR 42
TC 12
Z9 12
U1 0
U2 2
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0959-535X
J9 BRIT MED J
JI Br. Med. J.
PD AUG 25
PY 2011
VL 343
AR d5076
DI 10.1136/bmj.d5076
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA 813ZQ
UT WOS:000294410400003
PM 21868455
ER
PT J
AU Belgard, TG
Marques, AC
Oliver, PL
Abaan, HO
Sirey, TM
Hoerder-Suabedissen, A
Garcia-Moreno, F
Molnar, Z
Margulies, EH
Ponting, CP
AF Belgard, T. Grant
Marques, Ana C.
Oliver, Peter L.
Abaan, Hatice Ozel
Sirey, Tamara M.
Hoerder-Suabedissen, Anna
Garcia-Moreno, Fernando
Molnar, Zoltan
Margulies, Elliott H.
Ponting, Chris P.
TI A Transcriptomic Atlas of Mouse Neocortical Layers
SO NEURON
LA English
DT Article
ID LONG NONCODING RNAS; CAT VISUAL-CORTEX; GENE-EXPRESSION;
CEREBRAL-CORTEX; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; NMDA RECEPTORS;
HUMAN BRAIN; CELL-TYPES; NEURONS
AB In the mammalian cortex, neurons and glia form a patterned structure across six layers whose complex cytoarchitectonic arrangement is likely to contribute to cognition. We sequenced transcriptomes from layers 1-6b of different areas (primary and secondary) of the adult (postnatal day 56) mouse somatosensory cortex to understand the transcriptional levels and functional repertoires of coding and noncoding loci for cells constituting these layers. A total of 5,835 protein-coding genes and 66 noncoding RNA loci are differentially expressed ("patterned") across the layers, on the basis of a machine-learning model (naive Bayes) approach. Layers 2-6b are each associated with specific functional and disease annotations that provide insights into their biological roles. This new resource (http://genserv.anat.ox.ac.uk/layers) greatly extends currently available resources, such as the Allen Mouse Brain Atlas and microarray data sets, by providing quantitative expression levels, by being genome-wide, by including novel loci, and by identifying candidate alternatively spliced transcripts that are differentially expressed across layers.
C1 [Belgard, T. Grant; Sirey, Tamara M.; Hoerder-Suabedissen, Anna; Garcia-Moreno, Fernando; Molnar, Zoltan] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3QX, England.
[Belgard, T. Grant; Marques, Ana C.; Oliver, Peter L.; Sirey, Tamara M.; Ponting, Chris P.] Univ Oxford, MRC Funct Genom Unit, Oxford OX1 3QX, England.
[Belgard, T. Grant; Abaan, Hatice Ozel; Margulies, Elliott H.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
RP Molnar, Z (reprint author), Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3QX, England.
EM zoltan.molnar@dpag.ox.ac.uk; emargulies@illumina.com;
chris.ponting@dpag.ox.ac.uk
RI Hoerder-Suabedissen, Anna/G-7053-2011;
OI Marques, Ana Claudia/0000-0001-5174-8092; Hoerder-Suabedissen,
Anna/0000-0003-1953-7871; Molnar, Zoltan/0000-0002-6852-6004; Belgard,
Tildon/0000-0002-6962-7894; Ponting, Chris/0000-0003-0202-7816;
Garcia-Moreno, Fernando/0000-0001-9048-4237
FU Marshall Scholarship; New College, Oxford; NIH-Oxford-Cambridge; Marie
Curie Fellowship; National Human Genome Research Institute; MRC; BBSRC;
MAC; Wellcome Trust; St. John's College, Oxford; ERC
FX We thank W.Z. Wang, A.F. Cheung, and the NIH Intramural Sequencing
Center for technical assistance; R.A. Chodroff, E.D. Green, A. Heger, L.
Goodstadt, M. Goodson, C. Webber and J. Becker for helpful discussions.
T.G.B. was supported by a Marshall Scholarship; New College, Oxford; and
the NIH-Oxford-Cambridge Scholars Program. A.C.M. was supported by a
Marie Curie Fellowship. E.H.M. and H.O.A. were supported by the
Intramural Research Program of the National Human Genome Research
Institute. A.H-S. was supported by a MRC Programme Grant to ZM. T.M.S.
was supported by a BBSRC Project Grant to ZM and C.P.P. Z.M. was
supported by MAC, BBSRC, Wellcome Trust and St. John's College, Oxford.
P.L.O. was supported by the MRC and C.P.P. was supported by the MRC,
BBSRC and ERC.
NR 76
TC 116
Z9 121
U1 1
U2 18
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD AUG 25
PY 2011
VL 71
IS 4
BP 605
EP 616
DI 10.1016/j.neuron.2011.06.039
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 815JJ
UT WOS:000294521600007
PM 21867878
ER
PT J
AU Ciraci, E
Della Bella, S
Salvucci, O
Rofani, C
Segarra, M
Bason, C
Molinari, A
Maric, D
Tosato, G
Berardi, AC
AF Ciraci, Elisa
Della Bella, Silvia
Salvucci, Ombretta
Rofani, Cristina
Segarra, Marta
Bason, Caterina
Molinari, Agnese
Maric, Dragan
Tosato, Giovanna
Berardi, Anna C.
TI Adult human circulating CD34(-)Lin(-)CD45(-)CD133(-) cells can
differentiate into hematopoietic and endothelial cells
SO BLOOD
LA English
DT Article
ID HUMAN CORD BLOOD; BONE MARROW INJECTION; STEM-CELLS; PROGENITOR CELLS;
IN-VITRO; IDENTIFICATION; PRECURSORS; EXPRESSION; HEMANGIOBLAST; MICE
AB A precise identification of adult human hemangioblast is still lacking. To identify circulating precursors having the developmental potential of the hemangioblast, we established a new ex vivo long-term culture model supporting the differentiation of both hematopoietic and endothelial cell lineages. We identified from peripheral blood a population lacking the expression of CD34, lineage markers, CD45 and CD133 (CD34(-)Lin(-)CD45(-)CD133(-) cells), endowed with the ability to differentiate after a 6-week culture into both hematopoietic and endothelial lineages. The bilineage potential of CD34(-)Lin(-)CD45(-)CD133(-) cells was determined at the single-cell level in vitro and was confirmed by transplantation into NOD/SCID mice. In vivo, CD34(-)Lin(-)CD45(-)CD133(-) cells showed the ability to reconstitute hematopoietic tissue and to generate functional endothelial cells that contribute to new vessel formation during tumor angiogenesis. Molecular characterization of CD34(-)Lin(-)CD45(-)CD133(-) cells unveiled a stem cell profile compatible with both hematopoietic and endothelial potentials, characterized by the expression of c-Kit and CXCR4 as well as EphB4, EphB2, and ephrinB2. Further molecular and functional characterization of CD34(-)Lin(-)CD45(-)CD133(-) cells will help dissect their physiologic role in blood and blood vessel maintenance and repair in adult life. (Blood. 2011;118(8):2105-2115)
C1 [Ciraci, Elisa; Berardi, Anna C.] Spirito Santo Hosp, Dept Transfus Med, Lab Stem Cells, I-65100 Pescara, Italy.
[Della Bella, Silvia] Univ Milan, Dept Translat Med, Clin & Expt Immunol Lab, Milan, Italy.
[Della Bella, Silvia] IRCCS Ist Clin Humanitas, Milan, Italy.
[Salvucci, Ombretta; Segarra, Marta; Tosato, Giovanna] NCI, Ctr Canc Res, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA.
[Rofani, Cristina] Univ Roma La Sapienza, Dept Histol & Med Embryol, Rome, Italy.
[Bason, Caterina] Univ Verona, Dept Med, Sect Internal Med B, I-37100 Verona, Italy.
[Molinari, Agnese] Ist Super Sanita, Dept Technol & Hlth, I-00161 Rome, Italy.
[Maric, Dragan] Natl Inst Neurol Disorders & Stroke, Neurophysiol Lab, NIH, Bethesda, MD USA.
RP Berardi, AC (reprint author), Spirito Santo Hosp, Res Stem Cells Lab Transfus Med, Via Circuito, I-65100 Pescara, Italy.
EM annacberardi@yahoo.it
RI Molinari, Agnese/E-7588-2015;
OI Molinari, Agnese/0000-0002-9592-5465; Berardi, Anna
C./0000-0002-5078-6158; Della Bella, Silvia/0000-0003-0818-5049
FU "Associazione Italiana contro le Leucemie" (AIL) Pescara
FX This work was partially supported by "Associazione Italiana contro le
Leucemie" (AIL) Pescara.
NR 50
TC 14
Z9 14
U1 0
U2 9
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 25
PY 2011
VL 118
IS 8
BP 2105
EP 2115
DI 10.1182/blood-2010-10-316596
PG 11
WC Hematology
SC Hematology
GA 811ZR
UT WOS:000294258000013
PM 21715308
ER
PT J
AU Iglesias, MC
Almeida, JR
Fastenackels, S
van Bockel, DJ
Hashimoto, M
Venturi, V
Gostick, E
Urrutia, A
Wooldridge, L
Clement, M
Gras, S
Wilmann, PG
Autran, B
Moris, A
Rossjohn, J
Davenport, MP
Takiguchi, M
Brander, C
Douek, DC
Kelleher, AD
Price, DA
Appay, V
AF Iglesias, Maria Candela
Almeida, Jorge R.
Fastenackels, Solene
van Bockel, David J.
Hashimoto, Masao
Venturi, Vanessa
Gostick, Emma
Urrutia, Alejandra
Wooldridge, Linda
Clement, Mathew
Gras, Stephanie
Wilmann, Pascal G.
Autran, Brigitte
Moris, Arnaud
Rossjohn, Jamie
Davenport, Miles P.
Takiguchi, Masafumi
Brander, Christian
Douek, Daniel C.
Kelleher, Anthony D.
Price, David A.
Appay, Victor
TI Escape from highly effective public CD8(+) T-cell clonotypes by HIV
SO BLOOD
LA English
DT Article
ID LYMPHOCYTE RESPONSE; PEPTIDE-MHC; CONVERGENT RECOMBINATION; ANTIGEN
SENSITIVITY; SIV INFECTION; REPERTOIRE; RECEPTOR; CTL; ACTIVATION; VIRUS
AB Mapping the precise determinants of T-cell efficacy against viruses in humans is a public health priority with crucial implications for vaccine design. To inform this effort, we performed a comprehensive analysis of the effective CD8(+) T-cell clonotypes that constitute responses specific for the HIV p24 Gag-derived KK10 epitope (KRWIILGLNK; residues 263-272) restricted by HLA-B*2705, which are known to confer superior control of viral replication in HIV-infected individuals. Particular KK10-specific CD8(+) T-cell clonotypes, characterized by TRBV4-3/TRBJ1-3 gene rearrangements, were found to be preferentially selected in vivo and shared between individuals. These "public" clonotypes exhibit high levels of TCR avidity and Ag sensitivity, which impart functional advantages and enable effective suppression of HIV replication. The early L268M mutation at position 6 of the KK10 epitope enables the virus to avoid recognition by these highly effective CD8(+) T-cell clonotypes. However, alternative clonotypes with variant reactivity provide flexibility within the overall KK10-specific response. These findings provide refined mechanistic insights into the workings of an effective CD8(+) T-cell response against HIV. (Blood. 2011;118(8):2138-2149)
C1 [Iglesias, Maria Candela; Almeida, Jorge R.; Fastenackels, Solene; Urrutia, Alejandra; Autran, Brigitte; Moris, Arnaud; Appay, Victor] Univ Paris 06, Hop La Pitie Salpetriere, Avenir Grp, Inserm UMR S 945, Paris, France.
[Almeida, Jorge R.; Douek, Daniel C.; Price, David A.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[van Bockel, David J.; Kelleher, Anthony D.] Univ New S Wales, St Vincents Ctr Appl Med Res, Darlinghurst, NSW, Australia.
[van Bockel, David J.; Kelleher, Anthony D.] Univ New S Wales, Kirby Inst, Darlinghurst, NSW, Australia.
[Hashimoto, Masao; Takiguchi, Masafumi] Kumamoto Univ, Ctr AIDS Res, Div Viral Immunol, Kumamoto, Japan.
[Venturi, Vanessa] Univ New S Wales, Ctr Vasc Res, Computat Biol Grp, Kensington, NSW 2033, Australia.
[Gostick, Emma; Wooldridge, Linda; Clement, Mathew; Price, David A.] Cardiff Univ, Sch Med, Dept Infect Immun & Biochem, Cardiff, S Glam, Wales.
[Gras, Stephanie; Wilmann, Pascal G.; Rossjohn, Jamie] Monash Univ, Sch Biomed Sci, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia.
[Appay, Victor] Grp Hosp Pitie Salpetriere, AP HP, Lab Immunol Cellulaire & Tissulaire, F-75634 Paris, France.
[Davenport, Miles P.] Univ New S Wales, Ctr Vasc Res, Complex Syst Biol Grp, Kensington, NSW 2033, Australia.
[Brander, Christian] Hosp Univ Germans Trias & Pujol Ctra Canyet, AIDS Res Inst IrsiCaixa HIVACAT, Barcelona, Spain.
[Brander, Christian] ICREA, Barcelona, Spain.
RP Appay, V (reprint author), Univ Paris 06, Hop La Pitie Salpetriere, Avenir Grp, Inserm UMR S 945, Paris, France.
EM victor.appay@upmc.fr
RI gras, stephanie/C-8307-2013; Takiguchi, Masafumi/E-7468-2013; Rossjohn,
Jamie/F-9032-2013; Kumamoto University, CAIDS/G-8446-2013; Price,
David/C-7876-2013;
OI Rossjohn, Jamie/0000-0002-2020-7522; Price, David/0000-0001-9416-2737;
Ramos de Almeida, Jorge/0000-0002-5009-8478; Brander,
Christian/0000-0002-0548-5778; Moris, Arnaud/0000-0002-5052-1678
FU ANR [ANR-09-JCJC-0114-01]; Sidaction; Inserm; French ANRS; National
Institutes of Health via Vaccine Research Center (National Institute of
Allergy and Infectious Diseases [NIAID]) [R01 067077]; Australian
Research Council (ARC); Australian National Health and Medical Research
Council (NHMRC); UK Medical Research Council (MRC); Fundacao para a
Ciencia e Tecnologia
FX This work was supported by the ANR (project ANR-09-JCJC-0114-01),
Sidaction, the Inserm AVENIR grant, the French ANRS, the National
Institutes of Health via the Intramural Program of the Vaccine Research
Center (National Institute of Allergy and Infectious Diseases [NIAID])
and R01 067077 (C. B.), the Australian Research Council (ARC), the
Australian National Health and Medical Research Council (NHMRC), and the
UK Medical Research Council (MRC). M. C. I. is supported by a Sidaction
Fellowship. J.R.A. is supported by a Fundacao para a Ciencia e
Tecnologia Fellowship.
NR 50
TC 62
Z9 63
U1 0
U2 12
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 25
PY 2011
VL 118
IS 8
BP 2138
EP 2149
DI 10.1182/blood-2011-01-328781
PG 12
WC Hematology
SC Hematology
GA 811ZR
UT WOS:000294258000016
PM 21734237
ER
PT J
AU Walker, T
Johnson, PH
Moreira, LA
Iturbe-Ormaetxe, I
Frentiu, FD
McMeniman, CJ
Leong, YS
Dong, Y
Axford, J
Kriesner, P
Lloyd, AL
Ritchie, SA
O'Neill, SL
Hoffmann, AA
AF Walker, T.
Johnson, P. H.
Moreira, L. A.
Iturbe-Ormaetxe, I.
Frentiu, F. D.
McMeniman, C. J.
Leong, Y. S.
Dong, Y.
Axford, J.
Kriesner, P.
Lloyd, A. L.
Ritchie, S. A.
O'Neill, S. L.
Hoffmann, A. A.
TI The wMel Wolbachia strain blocks dengue and invades caged Aedes aegypti
populations
SO NATURE
LA English
DT Article
ID UNITED-STATES; VIRUS; INFECTION; MOSQUITO; DROSOPHILA; AUSTRALIA;
CULICIDAE; DIPTERA; MODELS; SPREAD
AB Dengue fever is the most important mosquito-borne viral disease of humans with more than 50 million cases estimated annually in more than 100 countries(1,2). Disturbingly, the geographic range of dengue is currently expanding and the severity of outbreaks is increasing(2-4). Control options for dengue are very limited and currently focus on reducing population abundance of the major mosquito vector, Aedes aegypti(5,6). These strategies are failing to reduce dengue incidence in tropical communities and there is an urgent need for effective alternatives. It has been proposed that endosymbiotic bacterial Wolbachia infections of insects might be used in novel strategies for dengue control(7-9). For example, the wMelPop-CLA Wolbachia strain reduces the lifespan of adult A. aegypti mosquitoes in stably transinfected lines(8). This life-shortening phenotype was predicted to reduce the potential for dengue transmission. The recent discovery that several Wolbachia infections, including wMelPop-CLA, can also directly influence the susceptibility of insects to infection with a range of insect and human pathogens(9-11) has markedly changed the potential for Wolbachia infections to control human diseases. Here we describe the successful transinfection of A. aegypti with the avirulent wMel strain of Wolbachia, which induces the reproductive phenotype cytoplasmic incompatibility with minimal apparent fitness costs and high maternal transmission, providing optimal phenotypic effects for invasion. Under semi-field conditions, the wMel strain increased from an initial starting frequency of 0.65 to near fixation within a few generations, invading A. aegypti populations at an accelerated rate relative to trials with the wMelPop-CLA strain. We also show that wMel and wMelPop-CLA strains block transmission of dengue serotype 2 (DENV-2) in A. aegypti, forming the basis of a practical approach to dengue suppression(12).
C1 [Walker, T.; Moreira, L. A.; Iturbe-Ormaetxe, I.; Frentiu, F. D.; McMeniman, C. J.; Leong, Y. S.; Dong, Y.; O'Neill, S. L.] Univ Queensland, Sch Biol Sci, Brisbane, Qld 4072, Australia.
[Axford, J.; Kriesner, P.; Hoffmann, A. A.] Univ Melbourne, Dept Genet, Inst Bio21, Melbourne, Vic 3010, Australia.
[Johnson, P. H.; Ritchie, S. A.] James Cook Univ, Sch Publ Hlth & Trop Med & Rehabil Sci, Cairns, Qld 4870, Australia.
[Lloyd, A. L.] N Carolina State Univ, Biomath Grad Program, Raleigh, NC 27695 USA.
[Lloyd, A. L.] N Carolina State Univ, Dept Math, Raleigh, NC 27695 USA.
[Lloyd, A. L.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[O'Neill, S. L.] Monash Univ, Sch Biol Sci, Clayton, Vic 3800, Australia.
RP O'Neill, SL (reprint author), Univ Queensland, Sch Biol Sci, Brisbane, Qld 4072, Australia.
EM scott.oneill@monash.edu
RI Lloyd, Alun/H-4944-2012; Frentiu, Francesca/K-4561-2012; Walker,
Thomas/F-6572-2013; Entomologiamolecular, Inct/J-8214-2013; Walker,
Thomas/B-9198-2014; Hoffmann, Ary/C-2961-2011; O'Neill,
Scott/B-3568-2009
OI Walker, Thomas/0000-0003-4475-5395; Walker, Thomas/0000-0002-3545-012X;
O'Neill, Scott/0000-0002-4131-3615
FU Foundation for the National Institutes of Health through the Grand
Challenges in Global Health Initiative of the Bill and Melinda Gates
Foundation; National Health and Medical Research Council, Australia;
NIH; Climate and Health Cluster of the CSIRO; Australian Research
Council
FX We are grateful to N. Kenny for technical support and to members of the
O'Neill laboratory for critical reading of the manuscript. We thank R.
Silcock, M. Janes, S. Long, C. Paton and C. Omodei for their assistance
in the semi-field cages and laboratory at James Cook University. We are
very grateful for all of our volunteers who helped to blood-feed the
mosquitoes in the cages and to P. Young for providing the anti-dengue
antibodies. This research was supported by a grant from the Foundation
for the National Institutes of Health through the Grand Challenges in
Global Health Initiative of the Bill and Melinda Gates Foundation, The
National Health and Medical Research Council, Australia, the RAPIDD
program of the NIH, the Climate and Health Cluster of the CSIRO Flagship
collaboration Fund and fellowships from the Australian Research Council.
NR 36
TC 346
Z9 366
U1 30
U2 169
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD AUG 25
PY 2011
VL 476
IS 7361
BP 450
EP U101
DI 10.1038/nature10355
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 811KT
UT WOS:000294209400036
PM 21866159
ER
PT J
AU Snyder, JS
Soumier, A
Brewer, M
Pickel, J
Cameron, HA
AF Snyder, Jason S.
Soumier, Amelie
Brewer, Michelle
Pickel, James
Cameron, Heather A.
TI Adult hippocampal neurogenesis buffers stress responses and depressive
behaviour
SO NATURE
LA English
DT Article
ID GLUCOCORTICOID-RECEPTOR; TRANSGENIC MICE; ANIMAL-MODEL; ASTROCYTES;
NEURONS; ANTIDEPRESSANTS; FOREBRAIN; LESIONS; BRAIN; RATS
AB Glucocorticoids are released in response to stressful experiences and serve many beneficial homeostatic functions. However, dysregulation of glucocorticoids is associated with cognitive impairments and depressive illness(1,2). In the hippocampus, a brain region densely populated with receptors for stress hormones, stress and glucocorticoids strongly inhibit adult neurogenesis(3). Decreased neurogenesis has been implicated in the pathogenesis of anxiety and depression, but direct evidence for this role is lacking(4,5). Here we show that adult-born hippocampal neurons are required for normal expression of the endocrine and behavioural components of the stress response. Using either transgenic or radiation methods to inhibit adult neurogenesis specifically, we find that glucocorticoid levels are slower to recover after moderate stress and are less suppressed by dexamethasone in neurogenesis-deficient mice than intact mice, consistent with a role for the hippocampus in regulation of the hypothalamic-pituitary-adrenal (HPA) axis(6,7). Relative to controls, neurogenesis-deficient mice also showed increased food avoidance in a novel environment after acute stress, increased behavioural despair in the forced swim test, and decreased sucrose preference, a measure of anhedonia. These findings identify a small subset of neurons within the dentate gyrus that are critical for hippocampal negative control of the HPA axis and support a direct role for adult neurogenesis in depressive illness.
C1 [Snyder, Jason S.; Soumier, Amelie; Brewer, Michelle; Pickel, James; Cameron, Heather A.] NIMH, NIH, Bethesda, MD 20892 USA.
RP Cameron, HA (reprint author), NIMH, NIH, Bethesda, MD 20892 USA.
EM heathercameron@mail.nih.gov
RI Snyder, Jason/F-3435-2011; Cameron, Heather/E-6221-2011;
OI Cameron, Heather/0000-0002-3245-5777; Snyder, Jason/0000-0002-5509-0272
FU National Institute of Mental Health, National Institutes of Health, USA
[ZIA MH002784]
FX We thank A. Sowers and J. Mitchell for help with irradiation, M. Brenner
for providing the plasmid construct, GlaxoSmithKline for providing the
antibody against HSV-TK, and K. Sanzone, F. Kamhi, L. Glover, S.
Ferrante and L. Grigereit for assisting with mouse breeding and
treatment. This research was supported by the Intramural Program of the
National Institute of Mental Health, National Institutes of Health, USA,
ZIA MH002784 (to H.A.C.).
NR 30
TC 458
Z9 478
U1 28
U2 161
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD AUG 25
PY 2011
VL 476
IS 7361
BP 458
EP U112
DI 10.1038/nature10287
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 811KT
UT WOS:000294209400038
PM 21814201
ER
PT J
AU Marom, M
Birnbaumer, L
Atlas, D
AF Marom, M.
Birnbaumer, L.
Atlas, D.
TI MEMBRANE DEPOLARIZATION COMBINED WITH Gq-ACTIVATED G-PROTEIN-COUPLED
RECEPTORS INDUCE TRANSIENT RECEPTOR POTENTIAL CHANNEL 1 (TRPC1)-
DEPENDENT POTENTIATION OF CATECHOLAMINE RELEASE
SO NEUROSCIENCE
LA English
DT Article
DE Ca(2+) channel; TRPC channel; Gq/11 GPCR; PLC beta;
depolarization-evoked secretion; LTP
ID ADRENAL CHROMAFFIN CELLS; RAT HIPPOCAMPAL-NEURONS; PIG CORONARY
MYOCYTES; GATED CALCIUM-CHANNEL; CA2+ SENSOR PROTEIN; NEUROTRANSMITTER
RELEASE; GUINEA-PIG; INTRACELLULAR CALCIUM; TRANSMITTER RELEASE;
CEREBELLAR NUCLEI
AB Agonists of the G(q/11)-activated G-protein-coupled receptors (GPCRs) combined with strong membrane depolarization (high KCI) induce a synergistic amplification of transmitter release. The molecular basis for the synergy is unknown. Here, we investigated this potentiated transmitter release (PTR) phenomenon at the single cell level by monitoring catecholamine (CA) release in chromaffin cells using amperometry. We found that the 60 mM KCI (K60)-triggered release in bovine chromaffin cells synergizes with bradykinin (BK) or histamine (Hist) to potentiate CA release. PTR was independent of Ca(2+) influx through voltage-gated calcium channels (VGCC), but required Ca(2+) at the extracellular medium and was abolished by inhibitors of phospholipase C beta (PLC beta). The similar to four-fold PTR induced in mouse chromaffin cells by BK and K60, was not observed in chromaffin cells prepared from TRPC1 KO mice and was restored by expressing hTRPC1. The synergy between strong voltage perturbation (K60) in the presence of VGCC blockers, and the activation of the G(q/11)-PLC beta signal-transduction cascade generates unique and fundamental amplified signaling machinery. The concerted activation of two independent cellular pathways could reinforce physiological signals that impinge on regulation of secretory events during repeated sequence of high-frequency excitation, hyperpolarization, and relief of inhibition such as long-term potentiation (LTP), that lead to neuronal synaptic plasticity. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.
C1 [Marom, M.; Atlas, D.] Hebrew Univ Jerusalem, Inst Life Sci, Dept Biol Chem, IL-91904 Jerusalem, Israel.
[Birnbaumer, L.] NIEHS, Neurobiol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Atlas, D (reprint author), Hebrew Univ Jerusalem, Inst Life Sci, Dept Biol Chem, IL-91904 Jerusalem, Israel.
EM datlas@vms.huji.ac.il
FU Betty Feffer foundation; H.L Lauterbach foundation
FX The authors thank Dr. B. Minke and M Peters for discussions, suggestions
and critically commenting on the work. This study was supported by The
Betty Feffer and The H.L Lauterbach foundations for D.A.
NR 68
TC 2
Z9 2
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4522
J9 NEUROSCIENCE
JI Neuroscience
PD AUG 25
PY 2011
VL 189
BP 132
EP 145
DI 10.1016/j.neuroscience.2011.05.007
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 809XT
UT WOS:000294090700013
PM 21621591
ER
PT J
AU Huskins, WC
O'Grady, NP
Goldmann, DA
AF Huskins, W. Charles
O'Grady, Naomi P.
Goldmann, Donald A.
TI Transmission of Resistant Bacteria in Intensive Care REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Huskins, W. Charles] Mayo Clin, Rochester, MN 55905 USA.
[O'Grady, Naomi P.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Goldmann, Donald A.] Harvard Univ, Sch Med, Boston, MA USA.
RP Huskins, WC (reprint author), Mayo Clin, Rochester, MN 55905 USA.
EM huskins.charles@mayo.edu
NR 1
TC 0
Z9 0
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD AUG 25
PY 2011
VL 365
IS 8
BP 764
EP 765
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 811JM
UT WOS:000294205300024
ER
PT J
AU Cherian, J
Choi, I
Nayyar, A
Manjunatha, UH
Mukherjee, T
Lee, YS
Boshoff, HI
Singh, R
Ha, YH
Goodwin, M
Lakshminarayana, SB
Niyomrattanakit, P
Jiricek, J
Rayindran, S
Dick, T
Keller, TH
Dartois, V
Barry, CE
AF Cherian, Joseph
Choi, Inhee
Nayyar, Arnit
Manjunatha, Ujjini H.
Mukherjee, Tathagata
Lee, Yong Sok
Boshoff, Helena I.
Singh, Ramandeep
Ha, Young Hwan
Goodwin, Michael
Lakshminarayana, Suresh B.
Niyomrattanakit, Pornwaratt
Jiricek, Jan
Rayindran, Sindhu
Dick, Thomas
Keller, Thomas H.
Dartois, Veronique
Barry, Clifton E., III
TI Structure-Activity Relationships of Antitubercular Nitroimidazoles. 3.
Exploration of the Linker and Lipophilic Tail of
((S)-2-Nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-6-yl)-(4-trifluoro
methoxybenzyl)amine (6-Amino PA-824).
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID MURINE MODEL; BACTERICIDAL ACTIVITY; MYCOBACTERIUM-TUBERCULOSIS;
IN-VITRO; PYRAZINAMIDE; ANALOGS; DRUG
AB The (S)-2-nitro-6-(4-(trifluoromethoxy)benzyloxy)-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine named PA-824 (1) has demonstrated antitubercular activity in vitro and in animal models and is currently in clinical trials. We synthesized derivatives at three positions of the 4-(trifluoromethoxy)benzylamino tail, and these were tested for whole-cell activity against both replicating and nonreplicating Mycobacterium tuberculosis (Mtb). In addition, we determined their kinetic parameters as substrates of the deazaflavin-dependent nitroreductase (Ddn) from Mtb that reductively activates these pro-drugs. These studies yielded multiple compounds with 40 nM aerobic whole cell activity and 1.6 mu M anaerobic whole cell activity: 10-fold improvements over both characteristics from the parent molecule. Some of these compounds exhibited enhanced solubility with acceptable stability to microsomal and in vivo metabolism. Analysis of the conformational preferences of these analogues using quantum chemistry suggests a preference for a pseudoequatorial orientation of the linker and lipophilic tail.
C1 [Cherian, Joseph; Manjunatha, Ujjini H.; Lakshminarayana, Suresh B.; Niyomrattanakit, Pornwaratt; Jiricek, Jan; Rayindran, Sindhu; Dick, Thomas; Keller, Thomas H.; Dartois, Veronique] Novartis Inst Trop Dis, Singapore 138670, Singapore.
[Choi, Inhee; Nayyar, Arnit; Mukherjee, Tathagata; Boshoff, Helena I.; Singh, Ramandeep; Ha, Young Hwan; Goodwin, Michael; Barry, Clifton E., III] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Lee, Yong Sok] NIH, Ctr Mol Modeling, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Barry, CE (reprint author), CEB3, Room 2W20D,Bldg 33,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM cbarry@mail.nih.gov
RI Barry, III, Clifton/H-3839-2012; Cherian, Joseph/Q-2522-2016;
OI Keller, Thomas/0000-0002-7553-6235
FU NIH, NIAID; NITD; Bill and Melinda Gates Foundation; Wellcome Trust; NIH
through the Center for Information Technology
FX This work was funded, in part, by the intramural research program of
NIH, NIAID, by NITD, and by a grant from the Bill and Melinda Gates
Foundation and the Wellcome Trust through the Grand Challenges in Global
Health Initiative. We thank Anne Goh and the bioanalytical team of NITD
for the determination of compound concentrations in microsomal and
plasma samples and Dr. Noel Whittaker, NIDDK, for HRMS of some of the
compounds. The quantum chemical study utilized PC/LINUX clusters at the
Center for Molecular Modeling of the NIH (http://cit.nih.gov), and this
research was also supported in part by the NIH Intramural Research
Program through the Center for Information Technology.
NR 25
TC 17
Z9 17
U1 0
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD AUG 25
PY 2011
VL 54
IS 16
BP 5639
EP 5659
DI 10.1021/jm1010644
PG 21
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 809SP
UT WOS:000294077300002
PM 21755942
ER
PT J
AU Hall, MD
Brimacombe, KR
Varonka, MS
Pluchino, KM
Monda, JK
Li, JY
Walsh, MJ
Boxer, MB
Warren, TH
Fales, HM
Gottesman, MM
AF Hall, Matthew D.
Brimacombe, Kyle R.
Varonka, Matthew S.
Pluchino, Kristen M.
Monda, Julie K.
Li, Jiayang
Walsh, Martin J.
Boxer, Matthew B.
Warren, Timothy H.
Fales, Henry M.
Gottesman, Michael M.
TI Synthesis and Structure-Activity Evaluation of
Isatin-beta-thiosemicarbazones with Improved Selective Activity toward
Multidrug-Resistant Cells Expressing P-Glycoprotein
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID CARCINOMA-CELLS; CANCER-CELLS; PHASE-I; TRANSPORTER; COMPLEXES;
TOXICITY; AGENTS; LINES; HYPERSENSITIVITY; 2-DEOXYGLUCOSE
AB Cancer multidrug resistance (MDR) mediated by ATP-binding cassette (ABC) transporters presents a significant unresolved clinical challenge. One strategy to resolve MDR is to develop compounds that selectively kill cells overexpressing the efflux transporter P-glycoprotein (MDR1, P-gp, ABCB1). We have previously reported structure-activity studies based around the lead compound NSC73306 (1, 1-isatin-4-(4'-methoxyphenyl)-3-thiosemicarbazone, 4.3-fold selective). Here we sought to extend this work on MDR1-selective analogues by establishing whether 1 showed "robust" activity against a range of cell lines expressing P-gp. We further aimed to synthesize and test analogues with varied substitution at the N4-position, and substitution around the N4-phenyl ring of isatin-beta-thiosemicarbazones (IBTs), to identify compounds with increased MDR1-selectivity. Compound 1 demonstrated MDR1-selectivity against all P-gp-expressing cell lines examined. This selectivity was reversed by inhibitors of P-gp ATPase activity. Structural variation at the 4'-phenyl position of 1 yielded compounds of greater MDR1-selectivity. Two of these analogues, 1-isatin-4-(4'-nitrophenyl)-3-thiosemicarbazone (22, 8.3-fold selective) and 1-isatin-4-(4'-tert-butyl phenyl)-3-thiosemicarbazone (32, 14.8-fold selective), were selected for further testing and were found to retain the activity profile of 1. These compounds are the most active IBTs identified to date.
C1 [Hall, Matthew D.; Brimacombe, Kyle R.; Pluchino, Kristen M.; Monda, Julie K.; Gottesman, Michael M.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Varonka, Matthew S.; Warren, Timothy H.] Georgetown Univ, Dept Chem, Washington, DC 20057 USA.
[Li, Jiayang; Fales, Henry M.] NHLBI, Lab Appl Mass Spectrometry, NIH, Bethesda, MD 20892 USA.
[Walsh, Martin J.; Boxer, Matthew B.] NIH, NIH Chem Genom Ctr, NIH Ctr Translat Therapeut, Bethesda, MD 20892 USA.
RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
EM gottesnun@mail.nih.gov
FU National Institutes of Health, National Cancer Institute
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute. We thank
George Leiman for editorial assistance.
NR 50
TC 43
Z9 43
U1 2
U2 12
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD AUG 25
PY 2011
VL 54
IS 16
BP 5878
EP 5889
DI 10.1021/jm2006047
PG 12
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 809SP
UT WOS:000294077300019
PM 21721528
ER
PT J
AU Ghosh, AK
Chapsal, BD
Parham, GL
Steffey, M
Agniswamy, J
Wang, YF
Amano, M
Weber, IT
Mitsuya, H
AF Ghosh, Arun K.
Chapsal, Bruno D.
Parham, Garth L.
Steffey, Melinda
Agniswamy, Johnson
Wang, Yuan-Fang
Amano, Masayuki
Weber, Irene T.
Mitsuya, Hiroaki
TI Design of HIV-1 Protease Inhibitors with C3-Substituted
Hexahydrocyclopentafuranyl Urethanes as P2-Ligands: Synthesis,
Biological Evaluation, and Protein-Ligand X-ray Crystal Structure
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID DRUG-RESISTANT MUTANTS; ANTIRETROVIRAL THERAPY; IN-VITRO; COMPLEXES;
BACKBONE; TMC114; POTENT; PI
AB We report the design, synthesis, biological evaluation, and the X-ray crystal structure of a novel inhibitor bound to the HIV-1 protease. Various C3-functionalized cyclopentanyltetrahydrofurans (Cp-THF) were designed to interact with the flap Gly48 carbonyl or amide NH in the S2-subsite of the HIV-1 protease. We investigated the potential of those functionalized ligands in combination with hydroxyethylsulfonamide isosteres. Inhibitor 26 containing a 3-(R)-hydroxyl group on the Cp-THF core displayed the most potent enzyme inhibitory and antiviral activity. Our studies revealed a preference for the 3-(R)-configuration over the corresponding 3-(S)-derivative. Inhibitor 26 exhibited potent activity against a panel of multidrug-resistant HIV-1 variants. A high resolution X-ray structure of 26-bound HIV-1 protease revealed important molecular insight into the ligand-binding site interactions.
C1 [Ghosh, Arun K.; Chapsal, Bruno D.; Parham, Garth L.; Steffey, Melinda] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA.
[Ghosh, Arun K.; Chapsal, Bruno D.; Parham, Garth L.; Steffey, Melinda] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA.
[Agniswamy, Johnson; Wang, Yuan-Fang; Weber, Irene T.] Georgia State Univ, Dept Biol, Atlanta, GA 30303 USA.
[Amano, Masayuki; Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Med & Pharmaceut Sci, Dept Hematol, Kumamoto 8608556, Japan.
[Amano, Masayuki; Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Med & Pharmaceut Sci, Dept Infect Dis, Kumamoto 8608556, Japan.
[Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA.
RP Ghosh, AK (reprint author), Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA.
EM akghosh@purdue.edu
RI Amano, Masayuki/N-7407-2016
OI Amano, Masayuki/0000-0003-0516-9502
FU National Institutes of Health [GM53386, GM62920]; Center for Cancer
Research, National Cancer Institute, National Institutes of Health;
Ministry of Education, Culture, Sports, Science, and Technology of Japan
(Monbu Kagakusho); Ministry of Health, Welfare, and Labor of Japan;
Grant to the Cooperative Research Project on Clinical and
Epidemiological Studies of Emerging and Reemerging Infectious Diseases
(Renkei Jigyo) of Monbu-Kagakusho
FX This research was supported by the National Institutes of Health (Grant
GM53386 to A.K.G. and Grant GM62920 to IT. W.). This work was also
supported by the Intramural Research Program of the Center for Cancer
Research, National Cancer Institute, National Institutes of Health, and
in part by a Grant-in-Aid for Scientific Research (Priority Areas) from
the Ministry of Education, Culture, Sports, Science, and Technology of
Japan (Monbu Kagakusho), a Grant for Promotion of AIDS Research from the
Ministry of Health, Welfare, and Labor of Japan, and the Grant to the
Cooperative Research Project on Clinical and Epidemiological Studies of
Emerging and Reemerging Infectious Diseases (Renkei Jigyo) of
Monbu-Kagakusho.
NR 33
TC 16
Z9 17
U1 0
U2 9
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD AUG 25
PY 2011
VL 54
IS 16
BP 5890
EP 5901
DI 10.1021/jm200649p
PG 12
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 809SP
UT WOS:000294077300020
PM 21800876
ER
PT J
AU Lee, KH
Shim, MS
Kim, JY
Jung, HK
Lee, E
Carlson, BA
Xu, XM
Park, JM
Hatfield, DL
Park, T
Lee, BJ
AF Lee, Kwang Hee
Shim, Myoung Sup
Kim, Jin Young
Jung, Hee Kyoung
Lee, Eunji
Carlson, Bradley A.
Xu, Xue-Ming
Park, Jin Mo
Hatfield, Dolph L.
Park, Taesung
Lee, Byeong Jae
TI Drosophila selenophosphate synthetase 1 regulates vitamin B6 metabolism:
prediction and confirmation
SO BMC GENOMICS
LA English
DT Article
ID SELENOCYSTEINE BIOSYNTHESIS; SELENOPROTEIN SYNTHESIS; 5'-PHOSPHATE
OXIDASE; ESCHERICHIA-COLI; GENE ONTOLOGY; SELENIUM; SYNTHASE; HOMOLOG;
PATHWAY; IDENTIFICATION
AB Background: There are two selenophosphate synthetases (SPSs) in higher eukaryotes, SPS1 and SPS2. Of these two isotypes, only SPS2 catalyzes selenophosphate synthesis. Although SPS1 does not contain selenophosphate synthesis activity, it was found to be essential for cell growth and embryogenesis in Drosophila. The function of SPS1, however, has not been elucidated.
Results: Differentially expressed genes in Drosophila SL2 cells were identified using two-way analysis of variance methods and clustered according to their temporal expression pattern. Gene ontology analysis was performed against differentially expressed genes and gene ontology terms related to vitamin B6 biosynthesis were found to be significantly affected at the early stage at which megamitochondria were not formed (day 3) after SPS1 knockdown. Interestingly, genes related to defense and amino acid metabolism were affected at a later stage (day 5) following knockdown. Levels of pyridoxal phosphate, an active form of vitamin B6, were decreased by SPS1 knockdown. Treatment of SL2 cells with an inhibitor of pyridoxal phosphate synthesis resulted in both a similar pattern of expression as that found by SPS1 knockdown and the formation of megamitochondria, the major phenotypic change observed by SPS1 knockdown.
Conclusions: These results indicate that SPS1 regulates vitamin B6 synthesis, which in turn impacts various cellular systems such as amino acid metabolism, defense and other important metabolic activities.
C1 [Lee, Kwang Hee; Shim, Myoung Sup; Kim, Jin Young; Jung, Hee Kyoung; Lee, Byeong Jae] Seoul Natl Univ, Dept Biol Sci, Seoul 151742, South Korea.
[Lee, Kwang Hee; Lee, Eunji; Park, Taesung; Lee, Byeong Jae] Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul 151742, South Korea.
[Lee, Eunji; Park, Taesung] Seoul Natl Univ, Dept Stat, Seoul 151742, South Korea.
[Carlson, Bradley A.; Xu, Xue-Ming; Hatfield, Dolph L.] NCI, Lab Canc Prevent, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Park, Jin Mo] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
[Park, Jin Mo] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Lee, BJ (reprint author), Seoul Natl Univ, Dept Biol Sci, Seoul 151742, South Korea.
EM imbglmg@snu.ac.kr
FU National Research Foundation of Korea (NRF); Ministry of Education,
Science and Technology [2009-0094020, 2011-0012947]; National Institutes
of Health, National Cancer Institute, Center for Cancer Research; Korea
Ministry of Education and Human Resources Development
FX This work was supported by the Priority Research Centers Program and
Basic Science Research Program through the National Research Foundation
of Korea (NRF) funded by the Ministry of Education, Science and
Technology (Grant Nos 2009-0094020 and 2011-0012947 to BJL) and in part
by the Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research. MSS, JYK, KHL and
HKJ were supported by Brain Korea 21 Research Fellowship from the Korea
Ministry of Education and Human Resources Development.
NR 45
TC 6
Z9 6
U1 1
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD AUG 24
PY 2011
VL 12
AR 426
DI 10.1186/1471-2164-12-426
PG 12
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 848KG
UT WOS:000297049900001
PM 21864351
ER
PT J
AU Zhang, CY
Elkahloun, AG
Robertson, M
Gills, JJ
Tsurutani, J
Shih, JH
Fukuoka, J
Hollander, MC
Harris, CC
Travis, WD
Jen, J
Dennis, PA
AF Zhang, Chunyu
Elkahloun, Abdel G.
Robertson, Matthew
Gills, Joell J.
Tsurutani, Junji
Shih, Joanna H.
Fukuoka, Junya
Hollander, M. Christine
Harris, Curtis C.
Travis, William D.
Jen, Jin
Dennis, Phillip A.
TI Loss of Cytoplasmic CDK1 Predicts Poor Survival in Human Lung Cancer and
Confers Chemotherapeutic Resistance
SO PLOS ONE
LA English
DT Article
ID BRONCHIAL EPITHELIAL-CELLS; CYCLIN-DEPENDENT KINASES; GENE-EXPRESSION;
EPIGENETIC INACTIVATION; MAMMARY TUMORIGENESIS; AKT ACTIVATION;
BREAST-CANCER; APOPTOSIS; CDC25A; PHOSPHORYLATION
AB The dismal lethality of lung cancer is due to late stage at diagnosis and inherent therapeutic resistance. The incorporation of targeted therapies has modestly improved clinical outcomes, but the identification of new targets could further improve clinical outcomes by guiding stratification of poor-risk early stage patients and individualizing therapeutic choices. We hypothesized that a sequential, combined microarray approach would be valuable to identify and validate new targets in lung cancer. We profiled gene expression signatures during lung epithelial cell immortalization and transformation, and showed that genes involved in mitosis were progressively enhanced in carcinogenesis. 28 genes were validated by immunoblotting and 4 genes were further evaluated in non-small cell lung cancer tissue microarrays. Although CDK1 was highly expressed in tumor tissues, its loss from the cytoplasm unexpectedly predicted poor survival and conferred resistance to chemotherapy in multiple cell lines, especially microtubule-directed agents. An analysis of expression of CDK1 and CDK1-associated genes in the NCI60 cell line database confirmed the broad association of these genes with chemotherapeutic responsiveness. These results have implications for personalizing lung cancer therapy and highlight the potential of combined approaches for biomarker discovery.
C1 [Zhang, Chunyu; Robertson, Matthew; Gills, Joell J.; Tsurutani, Junji; Hollander, M. Christine; Dennis, Phillip A.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Elkahloun, Abdel G.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
[Tsurutani, Junji] Kinki Univ, Sch Med, Dept Med Oncol, Osaka 589, Japan.
[Shih, Joanna H.] NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA.
[Fukuoka, Junya; Jen, Jin] NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA.
[Fukuoka, Junya] Toyama Univ Hosp, Dept Surg Pathol, Toyama, Japan.
[Harris, Curtis C.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Travis, William D.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA.
[Jen, Jin] Mayo Clin, Dept Pulm & Crit Care Med, Rochester, MN USA.
RP Zhang, CY (reprint author), Lovelace Resp Res Inst, COPD program, Albuquerque, NM USA.
EM dennisp@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 56
TC 14
Z9 15
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 24
PY 2011
VL 6
IS 8
AR e23849
DI 10.1371/journal.pone.0023849
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 832TW
UT WOS:000295832000067
PM 21887332
ER
PT J
AU Salgado, MT
Ramasamy, S
Tsuneshige, A
Manoharan, PT
Rifkind, JM
AF Salgado, Maria T.
Ramasamy, Somasundararn
Tsuneshige, Antonio
Manoharan, Periakaruppan T.
Rifkind, Joseph M.
TI A New Paramagnetic Intermediate Formed during the Reaction of Nitrite
with Deoxyhemoglobin
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID PROTEIN THIYL RADICALS; HYPOXIC CONDITIONS; HUMAN HEMOGLOBIN;
S-NITROSOHEMOGLOBIN; QUATERNARY STRUCTURE; BETA-93 CYSTEINE; VASCULAR
CONTROL; PLASMA NITRITE; OXIDE; REDUCTASE
AB The reduction of nitrite by deoxygenated hemoglobin chains has been implicated in red cell-induced vasodilation, although the mechanism for this process has not been established. We have previously demonstrated that the reaction of nitrite with deoxyhemoglobin produces a hybrid intermediate with properties of Hb(II)NO+ and Hb(III)NO that builds up during the reaction retaining potential NO bioactivity. To explain the unexpected stability of this intermediate, which prevents NO release from the Hb(III)NO component, we had implicated the transfer of an electron from the beta-93 thiol to NO+ producing center dot SHb(II)NO. To determine if this species is formed and to characterize its properties, we have investigated the electron paramagnetic resonance (EPR) changes taking place during the nitrite reaction. The EPR effects of blocking the thiol group with N-ethyl-maleimide and using carboxypeptidase-A to stabilize the R-quaternary conformation have demonstrated that center dot SHb(II)NO is formed and that it has the EPR spectrum expected for NO bound to the heme in the beta-chain plus that of a thiyl radical. This new NO-related paramagnetic species is in equilibrium with the hybrid intermediate "Hb(II)NO+ <-> Hb(III)NO", thereby further inhibiting the release of NO from Hb(II)NO. The formation of an NO-related paramagnetic species other than the tightly bound NO in Hb(II)NO was also confirmed by a decrease in the EPR signal by -20 degrees C incubation, which shifts the equilibrium back to the "Hb(II)NO+ <-> Hb(III)NO" intermediate. This previously unrecognized NO hemoglobin species explains the stability of the intermediates and the buildup of a pool of potentially bioactive NO during nitrite reduction. It also provides a pathway for the formation of beta-93 cysteine S-nitrosylated hemoglobin [SNOHb:S-nitrosohemoglobin], which has been shown to induce vasodilation, by a rapid radical radical-reaction of any free NO with the thiyl radical of this new paramagnetic intermediate.
C1 [Salgado, Maria T.; Ramasamy, Somasundararn; Rifkind, Joseph M.] NIA, Mol Dynam Sect, NIH, Baltimore, MD 21224 USA.
[Tsuneshige, Antonio] Hosei Univ, Fac Biosci & Appl Chem, Dept Frontier Biosci, Tokyo 1848584, Japan.
[Manoharan, Periakaruppan T.] IIT Madras, Dept Chem SAIF, Madras 600036, Tamil Nadu, India.
RP Rifkind, JM (reprint author), NIA, Mol Dynam Sect, NIH, Baltimore, MD 21224 USA.
EM rifkindj@mail.nih.gov
FU NIH, National Institute on Aging; DST, Government of India
[SR/S1/RFIC-02-2006]; India Gandhi National Open University, New Delhi
FX This research was supported by the Intramural Research Program of the
NIH, National Institute on Aging. We thank Dr. Antonio Tsuneshige for
providing the semihemoglobins samples for this study and Dr. Manoharan
for providing the spectra of T-state Hb(II)alpha NO and Hb(II)beta NO.
Dr. Manoharan acknowledges the Ramanna Fellowship (SR/S1/RFIC-02-2006)
from the DST, Government of India, and Sir C.V. Raman Chair
Professorship from India Gandhi National Open University, New Delhi.
NR 60
TC 12
Z9 13
U1 1
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD AUG 24
PY 2011
VL 133
IS 33
BP 13010
EP 13022
DI 10.1021/ja1115088
PG 13
WC Chemistry, Multidisciplinary
SC Chemistry
GA 816IG
UT WOS:000294591300031
PM 21755997
ER
PT J
AU Kleykamp, BA
Heishman, SJ
AF Kleykamp, Bethea A.
Heishman, Stephen J.
TI The Older Smoker
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID SMOKING-CESSATION; UNITED-STATES; ADULTS
C1 [Kleykamp, Bethea A.] NIDA, Intramural Res Program, Nicotine Psychopharmacol Sect, NIH, Baltimore, MD 21224 USA.
RP Kleykamp, BA (reprint author), NIDA, Intramural Res Program, Nicotine Psychopharmacol Sect, NIH, 251 Bayview Blvd,Ste 200, Baltimore, MD 21224 USA.
EM annie.kleykamp@nih.gov
FU Intramural NIH HHS [ZIA DA000483-08]
NR 10
TC 9
Z9 9
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD AUG 24
PY 2011
VL 306
IS 8
BP 876
EP 877
DI 10.1001/jama.2011.1221
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 810VY
UT WOS:000294157300027
PM 21862749
ER
PT J
AU Bell, AH
Malecek, NJ
Morin, EL
Hadj-Bouziane, F
Tootell, RBH
Ungerleider, LG
AF Bell, Andrew H.
Malecek, Nicholas J.
Morin, Elyse L.
Hadj-Bouziane, Fadila
Tootell, Roger B. H.
Ungerleider, Leslie G.
TI Relationship between Functional Magnetic Resonance Imaging-Identified
Regions and Neuronal Category Selectivity
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID INFERIOR TEMPORAL CORTEX; POSTERIOR INFEROTEMPORAL CORTEX; DISTRIBUTED
ORGANIZATION; OBJECT REPRESENTATIONS; BEHAVING MONKEYS; NEURAL
RESPONSES; CONTRAST AGENT; BODY PARTS; MACAQUE; FACE
AB Functional magnetic resonance imaging (fMRI) has been used extensively to identify regions in the inferiortemporal (IT) cortex that are selective for categories of visual stimuli. However, comparatively little is known about the neuronal responses relative to these fMRI-defined regions. Here, we compared in nonhuman primates the distribution and response properties of IT neurons recorded within versus outside fMRI regions selective for four different visual categories: faces, body parts, objects, and places. Although individual neurons that preferred each of the four categories were found throughout the sampled regions, they were most concentrated within the corresponding fMRI region, decreasing significantly within 1-4 mm from the edge of these regions. Furthermore, the correspondence between fMRI and neuronal distributions was specific to neurons that increased their firing rates in response to the visual stimuli but not to neurons suppressed by visual stimuli, suggesting that the processes associated with inhibiting neuronal activity did not contribute strongly to the fMRI signal in this experiment.
C1 [Bell, Andrew H.; Malecek, Nicholas J.; Morin, Elyse L.; Hadj-Bouziane, Fadila; Tootell, Roger B. H.; Ungerleider, Leslie G.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
[Tootell, Roger B. H.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Tootell, Roger B. H.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
RP Bell, AH (reprint author), MRC, Cognit & Brain Sci Unit, 15 Chaucer Rd, Cambridge CB2 7EF, England.
EM andrew.bell@mrc-cbu.cam.ac.uk
RI Hadj-Bouziane, Fadila/A-1180-2013;
OI Bell, Andrew/0000-0001-8420-4622
FU National Institutes of Health [R01 MH67529, R01 EY017081]; Athinoula A.
Martinos Center for Biomedical Imaging; National Center for Research
Resources; National Institute of Mental Health
FX This work was supported by National Institutes of Health Grants R01
MH67529 and R01 EY017081 (R.B.H.T.), the Athinoula A. Martinos Center
for Biomedical Imaging, the National Center for Research Resources, and
the National Institute of Mental Health Intramural Research Program
(A.H.B., N.J.M., E.L.M., F.H-B., and L.G.U.). We thank the following
individuals: Wim Vanduffel, Hauke Kolster, and Leeland Ekstrom for their
invaluable assistance with the imaging experiments conducted while at
Massachusetts General Hospital, and Lucy Guillory for her assistance
with animal training and collection of the imaging data.
NR 51
TC 47
Z9 47
U1 0
U2 7
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD AUG 24
PY 2011
VL 31
IS 34
BP 12229
EP 12240
DI 10.1523/JNEUROSCI.5865-10.2011
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 811IU
UT WOS:000294202900018
PM 21865466
ER
PT J
AU Steigelman, KA
Lelli, A
Wu, XD
Gao, JG
Lin, S
Piontek, K
Wodarczyk, C
Boletta, A
Kim, H
Qian, F
Germino, G
Geleoc, GSG
Holt, JR
Zuo, J
AF Steigelman, Katherine A.
Lelli, Andrea
Wu, Xudong
Gao, Jiangang
Lin, Susan
Piontek, Klaus
Wodarczyk, Claas
Boletta, Alessandra
Kim, Hyunho
Qian, Feng
Germino, Gregory
Geleoc, Gwenaelle S. G.
Holt, Jeffrey R.
Zuo, Jian
TI Polycystin-1 Is Required for Stereocilia Structure But Not for
Mechanotransduction in Inner Ear Hair Cells
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID KIDNEY-DISEASE; TRP CHANNELS; PKD1 GENE; IN-VIVO; TRANSDUCTION CHANNEL;
SENSORY TRANSDUCTION; EPITHELIAL-CELLS; CYST FORMATION; TIP-LINK;
PROTEIN
AB The polycystic kidney disease-1 (Pkd1) gene encodes a large transmembrane protein (polycystin-1, or PC-1) that is reported to function as a fluid flow sensor in the kidney. As a member of the transient receptor potential family, PC-1 has also been hypothesized to play a role in the elusive mechanoelectrical transduction (MET) channel in inner ear hair cells. Here, we analyze two independent mouse models of PC-1, a knock-in (KI) mutant line and a hair cell-specific inducible Cre-mediated knock-out line. Both models exhibit normal MET channel function at neonatal ages despite hearing loss and ultrastructural abnormalities of sterecilia that remain properly polarized at adult ages. These findings demonstrate that PC-1 plays an essential role in stereocilia structure and maintenance but not directly in MET channel function or planar cell polarity. We also demonstrate that PC-1 is colocalized with F-actin in hair cell stereocilia in vivo, using a hemagglutinin-tagged PC-1 KI mouse model, and in renal epithelial cell microvilli in vitro. These results not only demonstrate a novel role for PC-1 in the cochlea, but also suggest insight into the development of polycystic kidney disease.
C1 [Steigelman, Katherine A.; Wu, Xudong; Gao, Jiangang; Lin, Susan; Zuo, Jian] St Jude Childrens Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA.
[Steigelman, Katherine A.] Univ Tennessee, Ctr Hlth Sci, Dept Anat & Neurobiol, Memphis, TN 38163 USA.
[Lelli, Andrea; Geleoc, Gwenaelle S. G.; Holt, Jeffrey R.] Univ Virginia, Dept Neurosci, Charlottesville, VA 22908 USA.
[Piontek, Klaus; Kim, Hyunho; Qian, Feng; Germino, Gregory] Johns Hopkins Univ, Div Nephrol, Baltimore, MD 21205 USA.
[Wodarczyk, Claas; Boletta, Alessandra] Dibit San Raffaele Sci Inst, Dulbecco Telethon Inst, I-20132 Milan, Italy.
[Germino, Gregory] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Zuo, J (reprint author), St Jude Childrens Hosp, Dept Dev Biol, 262 Danny Thomas Pl, Memphis, TN 38105 USA.
EM jian.zuo@stjude.org
OI Germino, Gregory/0000-0002-3609-5588
FU NIH [1F31DC009393, DC06471, DC08800, CA21765, 5R25CA023944, DC006183,
DC05439, DK062199, DK090868, DK48006]; American Lebanese Syrian
Associated Charities; Hartwell Foundation; NIDDK; Johns Hopkins
Polycystic Kidney Disease Research; Office of Naval Research
[N000140911014]; Fondazione Telethon
FX This work was supported by NIH Grants 1F31DC009393 (K.S.), DC06471
(J.Z.), DC08800 (J.Z.), CA21765 (J.Z.), 5R25CA023944 (S.L.), DC006183
(G.S.G.G.), DC05439 (J.R.H.), DK062199 (Q.F.), DK090868 (Q.F.), and
DK48006 (G.G.), as well as the American Lebanese Syrian Associated
Charities, The Hartwell Foundation (J.Z.), the Intramural Research
Program of the NIDDK (G.G.), Johns Hopkins Polycystic Kidney Disease
Research, and Office of Naval Research Grant N000140911014 (J.Z.). We
thank Sharon Frase (St. Jude Children's Research Hospital, Memphis, TN),
Rich Martens (University of Alabama, Tuscaloosa, AL), and Lou Boykins
(University of Memphis, Memphis, TN) for their help and guidance with
scanning electron microscopy images; Stefan Heller (Stanford University,
Stanford, CA), Ulrich Mueller (Scripps Research Institute, La Jolla,
CA), James Bartles (Northwestern, Evanston, IL), and Peter Gillespie
(Oregon Hearing Research Center, Portland, OR) for sharing valuable
reagents (antibodies and constructs); Stanislav S. Zakharenko (St. Jude
Children's Research Hospital) for his discussion on protein
colocalization; and the Zuo lab, especially Dr. Brandon C. Cox, for
their helpful comments and suggestions.
NR 60
TC 14
Z9 14
U1 0
U2 6
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD AUG 24
PY 2011
VL 31
IS 34
BP 12241
EP 12250
DI 10.1523/JNEUROSCI.6531-10.2011
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 811IU
UT WOS:000294202900019
PM 21865467
ER
PT J
AU Abouyannis, M
Menten, J
Kiragga, A
Lynen, L
Robertson, G
Castelnuovo, B
Manabe, YC
Reynolds, SJ
Roberts, L
AF Abouyannis, Michael
Menten, Joris
Kiragga, Agnes
Lynen, Lutgarde
Robertson, Gavin
Castelnuovo, Barbara
Manabe, Yukari C.
Reynolds, Steven J.
Roberts, Lesley
TI Development and validation of systems for rational use of viral load
testing in adults receiving first-line ART in sub-Saharan Africa
SO AIDS
LA English
DT Article
DE antiretroviral therapy; HIV; resource-constrained settings; treatment
failure; Uganda; viral load
ID RESOURCE-LIMITED SETTINGS; ANTIRETROVIRAL TREATMENT FAILURE;
HIV-INFECTED ADULTS; IMMUNOLOGICAL CRITERIA; HIV-1-INFECTED ADULTS;
DISCORDANT RESPONSES; VIROLOGICAL FAILURE; THERAPY FAILURE; CELL COUNT;
MISCLASSIFICATION
AB Background: World Health Organization (WHO) immunological and clinical criteria for monitoring first-line antiretroviral treatment (ART) offer low accuracy for predicting viral failure. Targeting viral load assays to those at high risk has been recommended and a system to do this has been developed in Cambodia. Systems for use in sub-Saharan African populations were evaluated.
Methods: A new Ugandan-based scoring system for targeting viral load assays was developed from data from the first 4 years of a Ugandan cohort (N - 559) receiving first-line ART. The accuracy of this, the Cambodian system and the WHO criteria to predict viral failure, through targeting viral load assays, were compared in a separate population of 496 Ugandans.
Results: The new Ugandan scoring system included CD4 cell count, mean cell volume, adherence, and HIV-associated clinical events as predictors of viral failure. In the validation population, the Ugandan system undertook viral load assays in 61 (12.3%) cases offering 20.5% sensitivity and 100% positive predictive value (PPV) to predict viral failure. The Cambodian system undertook viral load assays in 33 (6.7%) cases producing 23.1% sensitivity and 90.0% PPV. WHO criteria recommended viral load assays in 72 (14.5%) cases offering 30.8% sensitivity and 100% PPV.
Conclusion: Locally developed algorithms based on clinical and immunological criteria may offer little additional accuracy over WHO criteria for targeting viral load assays. When possible, confirming viral load before switching therapy is recommended. Scoring systems are more flexible than WHO criteria in allowing ART providers to choose the proportion of the population that undergo targeted viral load testing. (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins
C1 [Abouyannis, Michael; Roberts, Lesley] Univ Birmingham, Birmingham B15 2TT, W Midlands, England.
[Menten, Joris; Lynen, Lutgarde] Inst Trop Med, B-2000 Antwerp, Belgium.
[Kiragga, Agnes; Robertson, Gavin; Castelnuovo, Barbara; Manabe, Yukari C.] Infect Dis Inst, Kampala, Uganda.
[Manabe, Yukari C.; Reynolds, Steven J.] Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA.
[Reynolds, Steven J.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Roberts, L (reprint author), Univ Birmingham, Birmingham B15 2TT, W Midlands, England.
EM l.m.roberts@bham.ac.uk
RI Lynen, Lutgarde/A-1212-2014
OI Lynen, Lutgarde/0000-0001-7183-4895
FU College of Medical and Dental Sciences, University of Birmingham;
Infectious Diseases Institute, Kampala, Uganda; Division of Intramural
Research, National Institute of Allergy and Infectious Diseases,
National Institutes of Health
FX The study was undertaken in part-fulfilment of an intercalated BmedSc
and M. A. was financially supported by the College of Medical and Dental
Sciences, University of Birmingham in this work. Funding was also
provided by the Infectious Diseases Institute, Kampala, Uganda and by
the Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health. All other authors
are employees of the institutions listed above and undertook activity as
part of their core role or as an additional activity.
NR 47
TC 18
Z9 18
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD AUG 24
PY 2011
VL 25
IS 13
BP 1627
EP 1635
DI 10.1097/QAD.0b013e328349a414
PG 9
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 801MB
UT WOS:000293441900008
PM 21673555
ER
PT J
AU Cadavid-Restrepo, G
Gastardelo, TS
Faudry, E
de Almeida, H
Bastos, IMD
Negreiros, RS
Lima, MM
Assumpcao, TC
Almeida, KC
Ragno, M
Ebel, C
Ribeiro, BM
Felix, CR
Santana, JM
AF Cadavid-Restrepo, Gloria
Gastardelo, Thiago S.
Faudry, Eric
de Almeida, Hugo
Bastos, Izabela M. D.
Negreiros, Raquel S.
Lima, Meire M.
Assumpcao, Teresa C.
Almeida, Keyla C.
Ragno, Michel
Ebel, Christine
Ribeiro, Bergmann M.
Felix, Carlos R.
Santana, Jaime M.
TI The major leucyl aminopeptidase of Trypanosoma cruzi (LAPTc) assembles
into a homohexamer and belongs to the M17 family of metallopeptidases
SO BMC BIOCHEMISTRY
LA English
DT Article
ID MAMMALIAN-CELL INVASION; LEUCINE AMINOPEPTIDASE; PROLYL OLIGOPEPTIDASE;
PARASITIC PROTOZOA; SEQUENCE ALIGNMENT; PROTEINASE; BRUCEI;
PURIFICATION; PEPTIDASES; INFECTION
AB Background: Pathogens depend on peptidase activities to accomplish many physiological processes, including interaction with their hosts, highlighting parasitic peptidases as potential drug targets. In this study, a major leucyl aminopeptidolytic activity was identified in Trypanosoma cruzi, the aetiological agent of Chagas disease.
Results: The enzyme was isolated from epimastigote forms of the parasite by a two-step chromatographic procedure and associated with a single 330-kDa homohexameric protein as determined by sedimentation velocity and light scattering experiments. Peptide mass fingerprinting identified the enzyme as the predicted T. cruzi aminopeptidase EAN97960. Molecular and enzymatic analysis indicated that this leucyl aminopeptidase of T. cruzi (LAPTc) belongs to the peptidase family M17 or leucyl aminopeptidase family. LAPTc has a strong dependence on neutral pH, is mesophilic and retains its oligomeric form up to 80 degrees C. Conversely, its recombinant form is thermophilic and requires alkaline pH.
Conclusions: LAPTc is a 330-kDa homohexameric metalloaminopeptidase expressed by all T. cruzi forms and mediates the major parasite leucyl aminopeptidolytic activity. Since biosynthetic pathways for essential amino acids, including leucine, are lacking in T. cruzi, LAPTc could have a function in nutritional supply.
C1 [Cadavid-Restrepo, Gloria; Gastardelo, Thiago S.; de Almeida, Hugo; Negreiros, Raquel S.; Lima, Meire M.; Assumpcao, Teresa C.; Almeida, Keyla C.; Ribeiro, Bergmann M.; Felix, Carlos R.; Santana, Jaime M.] Univ Brasilia, Dept Cell Biol, BR-70910900 Brasilia, DF, Brazil.
[Cadavid-Restrepo, Gloria] Univ Nacl Colombia, Dept Biosci, Nucleo El Volador, Medellin, Colombia.
[Faudry, Eric; Ragno, Michel] INSERM, Biol Canc & Infect IRTSV CEA, UMR1036, Grenoble, France.
[Faudry, Eric; Ragno, Michel] CNRS, Bacterial Pathogenesis & Cellular Responses ERL5, Grenoble, France.
[Faudry, Eric; Ragno, Michel; Ebel, Christine] Univ Grenoble 1, Grenoble, France.
[Bastos, Izabela M. D.] Univ Brasilia, Fac Ceilandia, BR-70910900 Brasilia, DF, Brazil.
[Assumpcao, Teresa C.] NIH, Lab Malaria & Vector Res, Rockville, MD 20852 USA.
[Ebel, Christine] CEA, Inst Biol Struct, F-38027 Grenoble, France.
[Ebel, Christine] CNRS, UMR 5075, Inst Biol Struct, F-38027 Grenoble, France.
RP Santana, JM (reprint author), Univ Brasilia, Dept Cell Biol, BR-70910900 Brasilia, DF, Brazil.
EM jsantana@unb.br
RI Faudry, Eric/I-9154-2014; RIBEIRO, BERGMANN/C-7114-2015; Santana,
Jaime/H-5319-2013;
OI de Almeida Silva, Hugo/0000-0003-3773-3251; Ribeiro,
Bergmann/0000-0002-1061-196X
FU CNPq; FINEP; FAP-DF; PRONEX; CAPES; UnB, Brazil
FX We thank Dr Marcelo Valle de Sousa from The University of Brasilia for
mass spectrometry analysis, and Aline Le Roy from the AUC and Protein
Analysis On Line (PAOL) platforms of the Partnership for Structural
Biology and the Institut de Biologie Structurale in Grenoble (PSB/IBS)
for performing experiments and analysis. This work was supported by
grants from CNPq, FINEP, FAP-DF, PRONEX, CAPES and UnB, Brazil.
NR 48
TC 10
Z9 10
U1 0
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2091
J9 BMC BIOCHEM
JI BMC Boichem.
PD AUG 23
PY 2011
VL 12
AR 46
DI 10.1186/1471-2091-12-46
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 824SL
UT WOS:000295222300002
PM 21861921
ER
PT J
AU Key, TJ
Appleby, PN
Reeves, GK
Roddam, AW
Helzlsouer, KJ
Alberg, AJ
Rollison, DE
Dorgan, JF
Brinton, LA
Overvad, K
Kaaks, R
Trichopoulou, A
Clavel-Chapelon, F
Panico, S
Duell, EJ
Peeters, PHM
Rinaldi, S
Riboli, E
Fentiman, IS
Dowsett, M
Manjer, J
Lenner, P
Hallmans, G
Baglietto, L
English, DR
Giles, GG
Hopper, JL
Severi, G
Morris, HA
Koenig, K
Zeleniuch-Jacquotte, A
Arslan, AA
Toniolo, P
Shore, RE
Krogh, V
Micheli, A
Berrino, F
Muti, P
Barrett-Connor, E
Laughlin, GA
Kabuto, M
Akiba, S
Stevens, RG
Neriishi, K
Land, CE
Cauley, JA
Lui, LY
Cummings, SR
Gunter, MJ
Rohan, TE
Strickler, HD
AF Key, T. J.
Appleby, P. N.
Reeves, G. K.
Roddam, A. W.
Helzlsouer, K. J.
Alberg, A. J.
Rollison, D. E.
Dorgan, J. F.
Brinton, L. A.
Overvad, K.
Kaaks, R.
Trichopoulou, A.
Clavel-Chapelon, F.
Panico, S.
Duell, E. J.
Peeters, P. H. M.
Rinaldi, S.
Riboli, E.
Fentiman, I. S.
Dowsett, M.
Manjer, J.
Lenner, P.
Hallmans, G.
Baglietto, L.
English, D. R.
Giles, G. G.
Hopper, J. L.
Severi, G.
Morris, H. A.
Koenig, K.
Zeleniuch-Jacquotte, A.
Arslan, A. A.
Toniolo, P.
Shore, R. E.
Krogh, V.
Micheli, A.
Berrino, F.
Muti, P.
Barrett-Connor, E.
Laughlin, G. A.
Kabuto, M.
Akiba, S.
Stevens, R. G.
Neriishi, K.
Land, C. E.
Cauley, J. A.
Lui, Li Yung
Cummings, Steven R.
Gunter, M. J.
Rohan, T. E.
Strickler, H. D.
CA Endogenous Hormones Breast Canc
TI Circulating sex hormones and breast cancer risk factors in
postmenopausal women: reanalysis of 13 studies
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE breast cancer; hormones; oestrogens; androgens; sex hormone-binding
globulin
ID LIFE-STYLE FACTORS; GROWTH-FACTOR-I; DEHYDROEPIANDROSTERONE-SULFATE;
CIGARETTE-SMOKING; ESTRADIOL LEVELS; SERUM CONCENTRATIONS; ADRENAL
ANDROGENS; BINDING GLOBULIN; STEROID-HORMONES; FAT DISTRIBUTION
AB BACKGROUND: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood.
METHODS: Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies.
RESULTS: Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer.
CONCLUSION: Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk. British Journal of Cancer (2011) 105, 709-722. doi:10.1038/bjc.2011.254 www.bjcancer.com Published online 19 July 2011 (C) 2011 Cancer Research UK
C1 [Key, T. J.; Appleby, P. N.; Reeves, G. K.; Roddam, A. W.] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England.
[Helzlsouer, K. J.; Alberg, A. J.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Helzlsouer, K. J.] Mercy Med Ctr, Prevent & Res Ctr, Baltimore, MD USA.
[Alberg, A. J.] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA.
[Rollison, D. E.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Interdisciplinary Oncol, Tampa, FL 33682 USA.
[Dorgan, J. F.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Dorgan, J. F.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Overvad, K.] Aarhus Univ Hosp, Dept Clin Epidemiol, DK-8000 Aarhus, Denmark.
[Kaaks, R.] DKFZ, Heidelberg, Germany.
[Trichopoulou, A.] Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, WHO Collaborating Ctr Food & Nutr Policies, GR-11527 Athens, Greece.
[Trichopoulou, A.] Hellen Hlth Fdn, Athens, Greece.
[Clavel-Chapelon, F.] INSERM, Ctr Res Epidemiol & Populat, U1018, Villejuif, France.
[Clavel-Chapelon, F.] Paris S Univ, UMRS1018, IGR, Villejuif, France.
[Panico, S.] Univ Naples Federico II, Dept Clin & Expt Med, Naples, Italy.
[Duell, E. J.] Catalan Inst Oncol, Unit Nutr Environm & Canc, Barcelona, Spain.
[Peeters, P. H. M.] Univ Med Ctr, Julius Ctr, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
[Peeters, P. H. M.; Riboli, E.] Univ London Imperial Coll Sci Technol & Med, London, England.
[Rinaldi, S.] Int Agcy Res Canc, F-69372 Lyon, France.
[Fentiman, I. S.] Guys Hosp, London SE1 9RT, England.
[Fentiman, I. S.] Inst Canc Res, Dept Biochem, London SW3 6JB, England.
[Manjer, J.] Malmo Univ Hosp, Dept Surg, Malmo, Sweden.
[Lenner, P.] Umea Univ, Dept Radiat Sci, Umea, Sweden.
[Hallmans, G.] Umea Univ Hosp, Dept Clin Med & Publ Hlth, Umea, Sweden.
[Baglietto, L.; English, D. R.; Giles, G. G.; Hopper, J. L.; Severi, G.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Koenig, K.; Zeleniuch-Jacquotte, A.] NYU, Sch Med, Dept Environm Med, New York, NY USA.
[Toniolo, P.] NYU, Sch Med, Dept Obstet & Gynecol, New York, NY USA.
[Shore, R. E.] Radiat Effects Res Fdn, Hiroshima, Japan.
[Krogh, V.; Micheli, A.; Berrino, F.] Fdn Ist Nazl Tumori, Milan, Italy.
[Muti, P.] Ist Nazl Tumori Regina Elena, Rome, Italy.
[Barrett-Connor, E.; Laughlin, G. A.] Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA.
[Kabuto, M.] Natl Inst Environm Studies, Environm Risk Res Div, Ibaraki, Japan.
[Akiba, S.] Kagoshima Univ, Fac Med, Dept Publ Hlth, Kagoshima 890, Japan.
[Stevens, R. G.] Univ Connecticut, Ctr Hlth, Dept Community Med, Farmington, CT USA.
[Neriishi, K.] Radiat Effects Res Fdn, Dept Clin Studies, Hiroshima, Japan.
[Land, C. E.] NCI, Radiat Epidemiol Branch, Bethesda, MD 20892 USA.
[Cauley, J. A.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA.
[Lui, Li Yung; Cummings, Steven R.] Calif Pacific Med Ctr, San Francisco Coordinating Ctr, San Francisco, CA USA.
[Lui, Li Yung; Cummings, Steven R.] San Francisco Coordinating Ctr, Study Osteoporot Fractures Res Grp, San Francisco, CA USA.
[Gunter, M. J.; Rohan, T. E.; Strickler, H. D.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA.
RP Key, TJ (reprint author), Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England.
EM tim.key@ceu.ox.ac.uk
RI Morris, Howard/G-4564-2010; Perez , Claudio Alejandro/F-8310-2010;
Clavel-Chapelon, Francoise/G-6733-2014; Brinton, Louise/G-7486-2015;
Krogh, Vittorio/K-2628-2016; Panico, Salvatore/K-6506-2016;
OI Giles, Graham/0000-0003-4946-9099; English, Dallas/0000-0001-7828-8188;
Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303; Tworoger,
Shelley/0000-0002-6986-7046; Cauley, Jane A/0000-0003-0752-4408; Perez ,
Claudio Alejandro/0000-0001-9688-184X; Brinton,
Louise/0000-0003-3853-8562; Krogh, Vittorio/0000-0003-0122-8624; Panico,
Salvatore/0000-0002-5498-8312; Duell, Eric J/0000-0001-5256-0163;
Micheli, Andrea/0000-0002-4558-4754
FU Cancer Research, UK [C570/A5028]
FX We thank the women who participated, the research staff and the
collaborating laboratories in each of the studies. This work was
supported by Cancer Research, UK (C570/A5028) for the central pooling
and analysis of the data; details of funding for the original studies
are in the relevant publications. The funders of the study had no role
in the study design, data collection, data analysis, data interpretation
or writing of the report. The authors had full access to all the data
and had final responsibility for the decision to submit the manuscript.
NR 80
TC 116
Z9 118
U1 3
U2 21
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
EI 1532-1827
J9 BRIT J CANCER
JI Br. J. Cancer
PD AUG 23
PY 2011
VL 105
IS 5
BP 709
EP 722
DI 10.1038/bjc.2011.254
PG 14
WC Oncology
SC Oncology
GA 811KG
UT WOS:000294207800017
ER
PT J
AU Barsov, EV
Trivett, MT
Minang, JT
Sun, HS
Ohlen, C
Ott, DE
AF Barsov, Eugene V.
Trivett, Matthew T.
Minang, Jacob T.
Sun, Haosi
Ohlen, Claes
Ott, David E.
TI Transduction of SIV-Specific TCR Genes into Rhesus Macaque CD8(+) T
Cells Conveys the Ability to Suppress SIV Replication
SO PLOS ONE
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; RECEPTOR GENES; VIRAL ESCAPE; RETROVIRAL
TRANSFER; CANCER REGRESSION; ADOPTIVE IMMUNOTHERAPY; EFFECTOR FUNCTIONS;
IMMUNE ESCAPE; LYMPHOCYTES; THERAPY
AB Background: The SIV/rhesus macaque model for HIV/AIDS is a powerful system for examining the contribution of T cells in the control of AIDS viruses. To better our understanding of CD8(+) T-cell control of SIV replication in CD4(+) T cells, we asked whether TCRs isolated from rhesus macaque CD8(+) T-cell clones that exhibited varying abilities to suppress SIV replication could convey their suppressive properties to CD8(+) T cells obtained from an uninfected/unvaccinated animal.
Principal Findings: We transferred SIV-specific TCR genes isolated from rhesus macaque CD8(+) T-cell clones with varying abilities to suppress SIV replication in vitro into CD8(+) T cells obtained from an uninfected animal by retroviral transduction. After sorting and expansion, transduced CD8(+) T-cell lines were obtained that specifically bound their cognate SIV tetramer. These cell lines displayed appropriate effector function and specificity, expressing intracellular IFN gamma upon peptide stimulation. Importantly, the SIV suppression properties of the transduced cell lines mirrored those of the original TCR donor clones: cell lines expressing TCRs transferred from highly suppressive clones effectively reduced wild-type SIV replication, while expression of a non-suppressing TCR failed to reduce the spread of virus. However, all TCRs were able to suppress the replication of an SIV mutant that did not downregulate MHC-I, recapitulating the properties of their donor clones.
Conclusions: Our results show that antigen-specific SIV suppression can be transferred between allogenic T cells simply by TCR gene transfer. This advance provides a platform for examining the contributions of TCRs versus the intrinsic effector characteristics of T-cell clones in virus suppression. Additionally, this approach can be applied to develop non-human primate models to evaluate adoptive T-cell transfer therapy for AIDS and other diseases.
C1 [Barsov, Eugene V.; Trivett, Matthew T.; Minang, Jacob T.; Sun, Haosi; Ohlen, Claes; Ott, David E.] NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
RP Barsov, EV (reprint author), NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
EM ottde@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This project has been funded 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
organization imply endorsement by the U.S. Government. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 72
TC 12
Z9 12
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 23
PY 2011
VL 6
IS 8
AR e23703
DI 10.1371/journal.pone.0023703
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 811YA
UT WOS:000294253500025
PM 21886812
ER
PT J
AU Hwang, CI
Matoso, A
Corney, DC
Flesken-Nikitin, A
Korner, S
Wang, W
Boccaccio, C
Thorgeirsson, SS
Comoglio, PM
Hermeking, H
Nikitin, AY
AF Hwang, Chang-Il
Matoso, Andres
Corney, David C.
Flesken-Nikitin, Andrea
Koerner, Stefanie
Wang, Wei
Boccaccio, Carla
Thorgeirsson, Snorri S.
Comoglio, Paolo M.
Hermeking, Heiko
Nikitin, Alexander Yu.
TI Wild-type p53 controls cell motility and invasion by dual regulation of
MET expression
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID OVARIAN-CANCER; MUTANT P53; C-MET; TRANSCRIPTIONAL ACTIVATION; SEROUS
CARCINOMA; GENE-EXPRESSION; DOWN-REGULATION; SP1; GROWTH; MUTATIONS
AB Recent observations suggest that p53 mutations are responsible not only for growth of primary tumors but also for their dissemination. However, mechanisms involved in p53-mediated control of cell motility and invasion remain poorly understood. By using the primary ovarian surface epithelium cell culture, we show that conditional inactivation of p53 or expression of its mutant forms results in overexpression of MET receptor tyrosine kinase, a crucial regulator of invasive growth. At the same time, cells acquire increased MET-dependent motility and invasion. Wild-type p53 negatively regulates MET expression by two mechanisms: (i) trans-activation of MET-targeting miR-34, and (ii) inhibition of SP1 binding to MET promoter. Both mechanisms are not functional in p53 absence, but mutant p53 proteins retain partial MET promoter suppression. Accordingly, MET overexpression, cell motility, and invasion are particularly high in p53-null cells. These results identify MET as a critical effector of p53 and suggest that inhibition of MET may be an effective antimetastatic approach to treat cancers with p53 mutations. These results also show that the extent of advanced cancer traits, such as invasion, may be determined by alterations in individual components of p53/MET regulatory network.
C1 [Hwang, Chang-Il; Matoso, Andres; Corney, David C.; Flesken-Nikitin, Andrea; Nikitin, Alexander Yu.] Cornell Univ, Dept Biomed Sci, Ithaca, NY 14853 USA.
[Wang, Wei] Cornell Univ, Microarray Core Facil, Ithaca, NY 14853 USA.
[Koerner, Stefanie; Hermeking, Heiko] Univ Munich, Inst Pathol, D-80337 Munich, Germany.
[Boccaccio, Carla; Comoglio, Paolo M.] Univ Turin, Sch Med, Div Mol Oncol, Inst Canc Res & Treatment, I-10060 Candiolo, Italy.
[Thorgeirsson, Snorri S.] NCI, NIH, Expt Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Nikitin, AY (reprint author), Cornell Univ, Dept Biomed Sci, Ithaca, NY 14853 USA.
EM an58@cornell.edu
OI Hwang, Chang-il/0000-0002-5710-7672; Boccaccio,
Carla/0000-0003-2620-9083; Comoglio, Paolo/0000-0002-7056-5328
FU National Institutes of Health [R01 CA96823, R01 CA112354]; Marsha Rivkin
Center for Ovarian Cancer; College of Veterinary Medicine, Cornell
University; Ovarian Cancer Research Fund
FX We thank Dr. Elena N. Shmidt, Dr. Irina N. Trofimova, Jessica Eng, and
Jane Ann for their technical help at the early stages of this project;
Dr. Stephen J. Weiss for critical reading of this manuscript; and Dr.
Anton Berns, Dr. Bert Vogelstein, and Dr. Samuel Mok for the generous
gifts of the p53fl/fl and Rbfl/fl mice, CMV-mutant
p53 constructs and plasmids PG13-luc and MG15-luc, and OVCA432 and
OVCA433 cell lines, respectively. This work was supported by National
Institutes of Health Grants R01 CA96823, R01 CA112354 and The Marsha
Rivkin Center for Ovarian Cancer funding (to A.Y.N.); a Graduate
Research Assistantship awarded by the College of Veterinary Medicine,
Cornell University (to C.-I.H.); and a Postdoctoral Fellowship awarded
by the Ovarian Cancer Research Fund (to A.M.).
NR 49
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U1 0
U2 8
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD AUG 23
PY 2011
VL 108
IS 34
BP 14240
EP 14245
DI 10.1073/pnas.1017536108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 810XO
UT WOS:000294163500074
PM 21831840
ER
PT J
AU Klepac, P
Laxminarayan, R
Grenfell, BT
AF Klepac, Petra
Laxminarayan, Ramanan
Grenfell, Bryan T.
TI Synthesizing epidemiological and economic optima for control of
immunizing infections
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE eradication threshold; transboundary model; resource allocation
ID QUANTITATIVE GUIDELINES; MEASLES ERADICATION; DISEASE; VACCINATION;
EPIDEMICS; POLIO; SMALLPOX; METAPOPULATIONS; ELIMINATION; STRATEGIES
AB Epidemic theory predicts that the vaccination threshold required to interrupt local transmission of an immunizing infection like measles depends only on the basic reproductive number R 0 and hence transmission rates. When the search for optimal strategies is expanded to incorporate economic constraints, the optimum for disease control in a single population is determined by relative costs of infection and control, rather than transmission rates. Adding a spatial dimension, which precludes local elimination unless it can be achieved globally, can reduce or increase optimal vaccination levels depending on the balance of costs and benefits. For weakly coupled populations, local optimal strategies agree with the global cost-effective strategy; however, asymmetries in costs can lead to divergent control optima in more strongly coupled systems-in particular, strong regional differences in costs of vaccination can preclude local elimination even when elimination is locally optimal. Under certain conditions, it is locally optimal to share vaccination resources with other populations.
C1 [Klepac, Petra; Grenfell, Bryan T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
[Laxminarayan, Ramanan] Princeton Univ, Princeton Environm Inst, Princeton, NJ 08544 USA.
[Grenfell, Bryan T.] Princeton Univ, Woodrow Wilson Sch Publ & Int Affairs, Princeton, NJ 08544 USA.
[Laxminarayan, Ramanan] Ctr Dis Dynam Econ & Policy, Washington, DC 20036 USA.
[Laxminarayan, Ramanan] Publ Hlth Fdn India, New Delhi 110070, India.
[Grenfell, Bryan T.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Klepac, P (reprint author), Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
EM pklepac@alum.mit.edu
FU Bill and Melinda Gates Foundation; Science and Technology Directorate,
Department of Homeland Security; Fogarty International Center, National
Institutes of Health; United Nations Educational, Scientific, and
Cultural Organization-L'Oreal for Women in Science Program
FX This research was supported by the Bill and Melinda Gates Foundation,
the Research and Policy for Infectious Disease Dynamics program of the
Science and Technology Directorate, Department of Homeland Security, and
the Fogarty International Center, National Institutes of Health (B.G.).
P. K. acknowledges support from the United Nations Educational,
Scientific, and Cultural Organization-L'Oreal for Women in Science
Program.
NR 48
TC 29
Z9 30
U1 0
U2 9
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD AUG 23
PY 2011
VL 108
IS 34
BP 14366
EP 14370
DI 10.1073/pnas.1101694108
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 810XO
UT WOS:000294163500095
PM 21825129
ER
PT J
AU Dulyaninova, NG
Hite, KM
Zencheck, WD
Scudiero, DA
Almo, SC
Shoemaker, RH
Bresnick, AR
AF Dulyaninova, Natalya G.
Hite, Karen M.
Zencheck, Wendy D.
Scudiero, Dominic A.
Almo, Steven C.
Shoemaker, Robert H.
Bresnick, Anne R.
TI Cysteine 81 Is Critical for the Interaction of S100A4 and Myosin-IIA
SO BIOCHEMISTRY
LA English
DT Article
ID METASTASIS-ASSOCIATED PROTEIN; CDC25 PHOSPHATASE INHIBITORS;
CALCIUM-BINDING PROTEIN; CRYSTAL-STRUCTURE; HEAVY-CHAIN; VITAMIN-K;
TARGET; PEPTIDE; FAMILY; POTENT
AB Overexpression of S100A4, a member of the S100 family of Ca2+-binding proteins, is associated with a number of human pathologies, including fibrosis, inflammatory disorders, and metastatic disease. The identification of small molecules that disrupt S100A4/target interactions provides a mechanism for inhibiting S100A4-mediated cellular activities and their associated pathologies. Using an anisotropy assay that monitors the Ca2+-dependent binding of myosin-IIA to S100A4, NSC 95397 was identified as an inhibitor that disrupts the S100A4/myosin-IIA interaction and inhibits S100A4-mediated depolymerization of myosin-ILA filaments. Mass spectrometry demonstrated that NSC 95397 forms covalent adducts with Cys81 and Cys86, which are located in the canonical target binding cleft. Mutagenesis studies showed that covalent modification of just Cys81 is sufficient to inhibit S100A4 function with respect to myosin-IIA binding and depolymerization. Remarkably, substitution of Cys81 with serine or alanine significantly impaired the ability of S100A4 to promote myosin-IIA filament disassembly. As reversible covalent cysteine modifications have been observed for several S100 proteins, we propose that modification of Cys81 may provide an additional regulatory mechanism for mediating the binding of S100A4 to myosin-IIA.
C1 [Dulyaninova, Natalya G.; Zencheck, Wendy D.; Almo, Steven C.; Bresnick, Anne R.] Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10461 USA.
[Hite, Karen M.; Scudiero, Dominic A.] Natl Canc Inst Frederick, SAIC Frederick, Frederick, MD 21702 USA.
[Shoemaker, Robert H.] Natl Canc Inst Frederick, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,Natl Inst Hlth, Frederick, MD 21702 USA.
RP Bresnick, AR (reprint author), Albert Einstein Coll Med, Dept Biochem, 1300 Morris Pk Ave, Bronx, NY 10461 USA.
EM anne.bresnick@einstein.yu.edu
FU National Institutes of Health [CA129598]; National Cancer Institute,
National Institutes of Health [HHSN26120080001E]
FX This work was supported in part with grants from the National Institutes
of Health grant CA129598 (A.R.B.) and in part with funds from the
National Cancer Institute, National Institutes of Health, under Contract
HHSN26120080001E.
NR 46
TC 10
Z9 10
U1 0
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD AUG 23
PY 2011
VL 50
IS 33
BP 7218
EP 7227
DI 10.1021/bi200853y
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 809SD
UT WOS:000294076100015
PM 21749055
ER
PT J
AU Nestorovich, EM
Karginov, VA
Popoff, MR
Bezrukov, SM
Barth, H
AF Nestorovich, Ekaterina M.
Karginov, Vladimir A.
Popoff, Michel R.
Bezrukov, Sergey M.
Barth, Holger
TI Tailored beta-Cyclodextrin Blocks the Translocation Pores of Binary
Exotoxins from C. Botulinum and C. Perfringens and Protects Cells from
Intoxication
SO PLOS ONE
LA English
DT Article
ID LIPID BILAYER-MEMBRANES; ANTHRAX TOXIN CHANNELS; SYMMETRICAL
TETRAALKYLAMMONIUM IONS; FLUORESCENCE-ACTIVATED CYTOMETRY;
VOLTAGE-DEPENDENT BLOCK; CURRENT NOISE-ANALYSIS; CLOSTRIDIUM-BOTULINUM;
C2 TOXIN; IOTA-TOXIN; ADP-RIBOSYLTRANSFERASE
AB Background: Clostridium botulinum C2 toxin and Clostridium perfringens iota toxin are binary exotoxins, which ADP-ribosylate actin in the cytosol of mammalian cells and thereby destroy the cytoskeleton. C2 and iota toxin consists of two individual proteins, an enzymatic active (A-) component and a separate receptor binding and translocation (B-) component. The latter forms a complex with the A-component on the surface of target cells and after receptor-mediated endocytosis, it mediates the translocation of the A-component from acidified endosomal vesicles into the cytosol. To this end, the B-components form heptameric pores in endosomal membranes, which serve as translocation channels for the A-components.
Methodology/Principal Findings: Here we demonstrate that a 7-fold symmetrical positively charged beta-cyclodextrin derivative, per-6-S-(3-aminomethyl) benzylthio-beta-cyclodextrin, protects cultured cells from intoxication with C2 and iota toxins in a concentration-dependent manner starting at low micromolar concentrations. We discovered that the compound inhibited the pH-dependent membrane translocation of the A-components of both toxins in intact cells. Consistently, the compound strongly blocked transmembrane channels formed by the B-components of C2 and iota toxin in planar lipid bilayers in vitro. With C2 toxin, we consecutively ruled out all other possible inhibitory mechanisms showing that the compound did not interfere with the binding of the toxin to the cells or with the enzyme activity of the A-component.
Conclusions/Significance: The described beta-cyclodextrin derivative was previously identified as one of the most potent inhibitors of the binary lethal toxin of Bacillus anthracis both in vitro and in vivo, implying that it might represent a broad-spectrum inhibitor of binary pore-forming exotoxins from pathogenic bacteria.
C1 [Nestorovich, Ekaterina M.] Catholic Univ Amer, Dept Biol, Washington, DC 20064 USA.
[Nestorovich, Ekaterina M.; Bezrukov, Sergey M.] NIH, Program Phys Biol, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
[Karginov, Vladimir A.] Innovat Biol Inc, Herndon, VA USA.
[Popoff, Michel R.] Inst Pasteur, Dept Host Pathogen Interact, Paris, France.
[Barth, Holger] Univ Ulm, Inst Pharmacol & Toxicol, Med Ctr, Ulm, Germany.
RP Nestorovich, EM (reprint author), Catholic Univ Amer, Dept Biol, Washington, DC 20064 USA.
EM holger.barth@uni-ulm.de
RI Barth, Holger/E-7920-2013; Popoff, Michel/O-7719-2016
OI Popoff, Michel/0000-0001-9305-8989
FU Deutsche Forschungsgemeinschaft DFG [BA 2087/2-1]; Catholic University
of America; Eunice Kennedy Shriver National Institute of Child Health
and Human Development; NIH; NIAID (National Institute of Allergy and
Infectious Diseases)
FX HB was financially supported by the Deutsche Forschungsgemeinschaft DFG
(http://www.dfg.de/) (grant BA 2087/2-1). EMN was supported by startup
funds from The Catholic University of America. EMN and SMB were
supported by the Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development, NIH
(http://www.nih.gov/) and NIAID (National Institute of Allergy and
Infectious Diseases; http://www.niaid.nih.gov) Intramural Biodefense
Research Grant for institutes other than NIAID (National Institute of
Allergy and Infectious Diseases; http://www.niaid.nih.gov). VAK is an
employee and shareholder of Innovative Biologics, Inc.; VAK provided the
substance (beta-cyclodextrin derivative) for this study. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 78
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U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 22
PY 2011
VL 6
IS 8
AR e23927
DI 10.1371/journal.pone.0023927
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 811XK
UT WOS:000294251800041
PM 21887348
ER
PT J
AU Berezhkovskii, A
Szabo, A
AF Berezhkovskii, Alexander
Szabo, Attila
TI Time scale separation leads to position-dependent diffusion along a slow
coordinate
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Article
DE diffusion; Markov processes; statistical mechanics
ID DYNAMICS; BARRIER; FLUID
AB When there is a separation of time scales, an effective description of the dynamics of the slow variables can be obtained by adiabatic elimination of fast ones. For example, for anisotropic Langevin dynamics in two dimensions, the conventional procedure leads to a Langevin equation for the slow coordinate that involves the potential of the mean force. The friction constant along this coordinate remains unchanged. Here, we show that a more accurate, but still Markovian, description of the slow dynamics can be obtained by using position-dependent friction that is related to the time integral of the autocorrelation function of the difference between the actual force and the mean force by a Kirkwood-like formula. The result is generalized to many dimensions, where the slow or reaction coordinate is an arbitrary function of the Cartesian coordinates. When the fast variables are effectively one-dimensional, the additional friction along the slow coordinate can be expressed in closed form for an arbitrary potential. For a cylindrically symmetric channel of varying cross section with winding centerline, our analytical expression immediately yields the multidimensional version of the Zwanzig-Bradley formula for the position-dependent diffusion coefficient. [doi:10.1063/1.3626215]
C1 [Berezhkovskii, Alexander] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Szabo, Attila] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Berezhkovskii, A (reprint author), NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA.
EM berezh@mail.nih.gov
RI Szabo, Attila/H-3867-2012
FU NIH, Center for Information Technology; National Institute of Diabetes
and Digestive and Kidney Diseases
FX We thank Gerhard Hummer for his comments on the manuscript. This study
was supported by the Intramural Research Program of the NIH, Center for
Information Technology and National Institute of Diabetes and Digestive
and Kidney Diseases.
NR 18
TC 43
Z9 43
U1 1
U2 30
PU AMER INST PHYSICS
PI MELVILLE
PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1,
MELVILLE, NY 11747-4501 USA
SN 0021-9606
J9 J CHEM PHYS
JI J. Chem. Phys.
PD AUG 21
PY 2011
VL 135
IS 7
AR 074108
DI 10.1063/1.3626215
PG 5
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 809NY
UT WOS:000294065200012
PM 21861557
ER
PT J
AU Berezhkovskii, AM
Szabo, A
Zhou, HX
AF Berezhkovskii, Alexander M.
Szabo, Attila
Zhou, Huan-Xiang
TI Diffusion-influenced ligand binding to buried sites in macromolecules
and transmembrane channels
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Article
DE biochemistry; biodiffusion; biomembranes; enzymes; macromolecules;
molecular biophysics
ID TIME-DEPENDENT RATE; ACTIVE-SITE; ORIENTATION CONSTRAINTS; PROTON
CHANNEL; ASSOCIATION; MECHANISM; KINETICS; RECEPTORS; SURFACE
AB We consider diffusion-influenced binding to a buried binding site that is connected to the surface by a narrow tunnel. Under the single assumption of an equilibrium distribution of ligands over the tunnel cross section, we reduce the calculation of the time-dependent rate coefficient to the solution of a one-dimensional diffusion equation with appropriate boundary conditions. We obtain a simple analytical expression for the steady-state rate that depends on the potential of mean force in the tunnel and the diffusion-controlled rate of binding to the tunnel entrance. Potential applications of our theory include substrate binding to a buried active site of an enzyme and permeant ion binding to an internal site in a transmembrane channel. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3609973]
C1 [Berezhkovskii, Alexander M.] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Szabo, Attila] Natl Inst Digest & Kidney Dis, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Zhou, Huan-Xiang] Florida State Univ, Dept Phys, Tallahassee, FL 32306 USA.
[Zhou, Huan-Xiang] Florida State Univ, Inst Mol Biophys, Tallahassee, FL 32306 USA.
RP Berezhkovskii, AM (reprint author), NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA.
EM berezh@mail.nih.gov
RI Szabo, Attila/H-3867-2012; Zhou, Huan-Xiang/M-5170-2016
OI Zhou, Huan-Xiang/0000-0001-9020-0302
FU NIH, Center for Information Technology; National Institute of Diabetes
and Digestive and Kidney Diseases; National Institutes of Health (NIH)
[GM58187, AI23007]
FX This study was supported by the Intramural Research Program of the NIH,
Center for Information Technology and National Institute of Diabetes and
Digestive and Kidney Diseases, and by grants GM58187 and AI23007 from
the National Institutes of Health (NIH).
NR 28
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U1 1
U2 11
PU AMER INST PHYSICS
PI MELVILLE
PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1,
MELVILLE, NY 11747-4501 USA
SN 0021-9606
J9 J CHEM PHYS
JI J. Chem. Phys.
PD AUG 21
PY 2011
VL 135
IS 7
AR 075103
DI 10.1063/1.3609973
PG 5
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 809NY
UT WOS:000294065200041
PM 21861586
ER
PT J
AU Berezhkovskii, AM
AF Berezhkovskii, Alexander M.
TI Ordinary differential equation for local accumulation time
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Article
DE biochemistry; biological tissues; cellular biophysics; macromolecules;
molecular biophysics; partial differential equations; reaction-diffusion
systems
ID MORPHOGEN GRADIENT; DIFFUSION
AB Cell differentiation in a developing tissue is controlled by the concentration fields of signaling molecules called morphogens. Formation of these concentration fields can be described by the reaction-diffusion mechanism in which locally produced molecules diffuse through the patterned tissue and are degraded. The formation kinetics at a given point of the patterned tissue can be characterized by the local accumulation time, defined in terms of the local relaxation function. Here, we show that this time satisfies an ordinary differential equation. Using this equation one can straightforwardly determine the local accumulation time, i.e., without preliminary calculation of the relaxation function by solving the partial differential equation, as was done in previous studies. We derive this ordinary differential equation together with the accompanying boundary conditions and demonstrate that the earlier obtained results for the local accumulation time can be recovered by solving this equation. [doi:10.1063/1.3624898]
C1 NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Berezhkovskii, AM (reprint author), NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA.
FU National Institutes of Health (NIH), Center for Information Technology
FX The author is grateful to Stas Shvartsman for numerous illuminating
discussions of different aspects of the problem. This study was
supported by the Intramural Research Program of the National Institutes
of Health (NIH), Center for Information Technology.
NR 18
TC 8
Z9 8
U1 0
U2 3
PU AMER INST PHYSICS
PI MELVILLE
PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1,
MELVILLE, NY 11747-4501 USA
SN 0021-9606
J9 J CHEM PHYS
JI J. Chem. Phys.
PD AUG 21
PY 2011
VL 135
IS 7
AR 074112
DI 10.1063/1.3624898
PG 5
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 809NY
UT WOS:000294065200016
PM 21861561
ER
PT J
AU Woody, GE
Metzger, DS
AF Woody, George E.
Metzger, David S.
TI Injectable extended-release naltrexone for opioid dependence
SO LANCET
LA English
DT Letter
ID PHARMACOTHERAPIES
C1 [Woody, George E.] Univ Penn, Philadelphia, PA 19106 USA.
NIDA Clin Trials Network, Philadelphia, PA 19106 USA.
RP Woody, GE (reprint author), Univ Penn, Philadelphia, PA 19106 USA.
EM woody@tresearch.org
NR 5
TC 5
Z9 5
U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
J9 LANCET
JI Lancet
PD AUG 20
PY 2011
VL 378
IS 9792
BP 664
EP 665
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 815EW
UT WOS:000294509900022
PM 21856476
ER
PT J
AU Oza, AM
Elit, L
Tsao, MS
Kamel-Reid, S
Biagi, J
Provencher, DM
Gotlieb, WH
Hoskins, PJ
Ghatage, P
Tonkin, KS
Mackay, HJ
Mazurka, J
Sederias, J
Ivy, P
Dancey, JE
Eisenhauer, EA
AF Oza, Amit M.
Elit, Laurie
Tsao, Ming-Sound
Kamel-Reid, Suzanne
Biagi, Jim
Provencher, Diane Michele
Gotlieb, Walter H.
Hoskins, Paul J.
Ghatage, Prafull
Tonkin, Katia S.
Mackay, Helen J.
Mazurka, John
Sederias, Joana
Ivy, Percy
Dancey, Janet E.
Eisenhauer, Elizabeth A.
TI Phase II Study of Temsirolimus in Women With Recurrent or Metastatic
Endometrial Cancer: A Trial of the NCIC Clinical Trials Group
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID GYNECOLOGIC-ONCOLOGY-GROUP; MEDROXYPROGESTERONE ACETATE; MAMMALIAN
TARGET; PTEN EXPRESSION; CARCINOMA; TAMOXIFEN; ADENOCARCINOMA;
PACLITAXEL; MUTATIONS; TUMORS
AB Purpose Phosphatase and tensin homolog (PTEN) is a tumor suppressor gene, and loss of function mutations are common and appear to be important in the pathogenesis of endometrial carcinomas. Loss of PTEN causes deregulated phosphatidylinositol-3 kinase/serine-threonine kinase/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling which may provide neoplastic cells with a selective survival advantage by enhancing angiogenesis, protein translation, and cell cycle progression. Temsirolimus, an ester derivative of rapamycin that inhibits mTOR, was evaluated in this setting.
Patients and Methods Sequential phase II studies evaluated single-agent activity of temsirolimus in women with recurrent or metastatic chemotherapy-naive or chemotherapy-treated endometrial cancer. Temsirolimus 25 mg intravenously was administered weekly in 4-week cycles.
Results In the chemotherapy-naive group, 33 patients received a median of four cycles (range, one to 23 cycles). Of the 29 patients evaluable for response, four (14%) had an independently confirmed partial response and 20 (69%) had stable disease as best response, with a median duration of 5.1 months (range, 3.7 to 18.4 months) and 9.7 months (range, 2.1 to 14.6 months). Only five patients (18%) had progressive disease. In the chemotherapy-treated group, 27 patients received a median of three cycles (range, one to six cycles). Of the 25 patients evaluable for response, one (4%) had an independently confirmed partial response, and 12 patients (48%) had stable disease, with a median duration of 4.3 months (range, 3.6 to 4.9 months) and 3.7 months (range, 2.4 to 23.2 months). PTEN loss (immunohistochemistry and mutational analysis) and molecular markers of PI3K/Akt/mTOR pathway did not correlate with the clinical outcome.
Conclusion mTOR inhibition with temsirolimus has encouraging single-agent activity in endometrial cancer which is higher in chemotherapy-naive patients than in chemotherapy-treated patients and is independent of PTEN status. The difference in activity according to prior therapy should be factored into future clinical trial designs. J Clin Oncol 29:3278-3285. (C) 2011 by American Society of Clinical Oncology
C1 [Oza, Amit M.; Tsao, Ming-Sound; Kamel-Reid, Suzanne; Mackay, Helen J.] Univ Toronto, Princess Margaret Hosp, Univ Hlth Network, Toronto, ON M5G 2M9, Canada.
[Sederias, Joana; Dancey, Janet E.; Eisenhauer, Elizabeth A.] Queens Univ, NCIC Clin Trials Grp, Kingston, ON, Canada.
[Provencher, Diane Michele] Ctr Hosp Univ Montreal, Montreal, PQ, Canada.
[Gotlieb, Walter H.] McGill Univ, Segal Canc Ctr, Montreal, PQ, Canada.
[Hoskins, Paul J.] British Columbia Canc Agcy Vancouver Clin, Vancouver, BC, Canada.
[Ghatage, Prafull] Tom Baker Canc Clin, Calgary, AB, Canada.
[Tonkin, Katia S.] Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada.
[Ivy, Percy] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Oza, AM (reprint author), Univ Toronto, Princess Margaret Hosp, Univ Hlth Network, 610 Univ Ave,Suite 5-700, Toronto, ON M5G 2M9, Canada.
EM amit.oza@uhn.on.ca
FU Canadian Cancer Society [021039]
FX Supported by Grant No. 021039 from the Canadian Cancer Society to the
NCIC Clinical Trials Group. Drugs were supplied by the Cancer
Therapeutics Evaluation Program, National Cancer Institute, Bethesda,
MD.
NR 36
TC 136
Z9 140
U1 1
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD AUG 20
PY 2011
VL 29
IS 24
BP 3278
EP 3285
DI 10.1200/JCO.2010.34.1578
PG 8
WC Oncology
SC Oncology
GA 808VD
UT WOS:000294008500021
PM 21788564
ER
PT J
AU Pinsky, PF
AF Pinsky, Paul F.
TI Point Estimates of Number Needed to Treat/Screen Are Insufficient
Without Characterization of Their Uncertainty
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
C1 NCI, NIH, Bethesda, MD 20892 USA.
RP Pinsky, PF (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
NR 1
TC 2
Z9 2
U1 1
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD AUG 20
PY 2011
VL 29
IS 24
BP 3336
EP 3336
DI 10.1200/JCO.2011.36.4554
PG 1
WC Oncology
SC Oncology
GA 808VD
UT WOS:000294008500034
PM 21768452
ER
PT J
AU Loeb, S
Vonesh, EF
Metter, EJ
Carter, HB
Gann, PH
Catalona, WJ
AF Loeb, Stacy
Vonesh, Edward F.
Metter, E. Jeffrey
Carter, H. Ballentine
Gann, Peter H.
Catalona, William J.
TI Point Estimates of Number Needed to Treat/Screen Are Insufficient
Without Characterization of Their Uncertainty Reply
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
ID MORTALITY
C1 [Loeb, Stacy; Carter, H. Ballentine] Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA.
[Vonesh, Edward F.; Catalona, William J.] NW Feinberg Sch Med, Chicago, IL USA.
[Metter, E. Jeffrey] NIA, Baltimore, MD 21224 USA.
[Gann, Peter H.] Univ Illinois, Chicago, IL USA.
RP Loeb, S (reprint author), Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA.
NR 4
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD AUG 20
PY 2011
VL 29
IS 24
BP 3337
EP 3337
DI 10.1200/JCO.2011.36.5395
PG 1
WC Oncology
SC Oncology
GA 808VD
UT WOS:000294008500035
ER
PT J
AU Joo, JH
Dorsey, FC
Joshi, A
Hennessy-Walters, KM
Rose, KL
McCastlain, K
Zhang, J
Iyengar, R
Jung, CH
Suen, DF
Steeves, MA
Yang, CY
Prater, SM
Kim, DH
Thompson, CB
Youle, RJ
Ney, PA
Cleveland, JL
Kundu, M
AF Joo, Joung Hyuck
Dorsey, Frank C.
Joshi, Aashish
Hennessy-Walters, Kristin M.
Rose, Kristie L.
McCastlain, Kelly
Zhang, Ji
Iyengar, Rekha
Jung, Chang Hwa
Suen, Der-Fen
Steeves, Meredith A.
Yang, Chia-Ying
Prater, Stephanie M.
Kim, Do-Hyung
Thompson, Craig B.
Youle, Richard J.
Ney, Paul A.
Cleveland, John L.
Kundu, Mondira
TI Hsp90-Cdc37 Chaperone Complex Regulates Ulk1-and Atg13-Mediated
Mitophagy
SO MOLECULAR CELL
LA English
DT Article
ID AUTOPHAGY INHIBITION; CANCER-TREATMENT; MOUSE MODELS; HSP90;
MITOCHONDRIA; PARKIN; DEGRADATION; MUTATIONS; MECHANISM; DISEASE
AB Autophagy, the primary recycling pathway of cells, plays a critical role in mitochondrial quality control under normal growth conditions and in the response to cellular stress. The Hsp90-Cdc37 chaperone complex coordinately regulates the activity of select kinases to orchestrate many facets of the stress response. Although both maintain mitochondrial integrity, the relationship between Hsp90-Cdc37 and autophagy has not been well characterized. Ulk1, one of the mammalian homologs of yeast Atg1, is a serine-threonine kinase required for mitophagy. Here we show that the interaction between Ulk1 and Hsp90-Cdc37 stabilizes and activates Ulk1, which in turn is required for the phosphorylation and release of Atg13 from Ulk1, and for the recruitment of Atg13 to damaged mitochondria. Hsp90-Cdc37, Ulk1, and Atg13 phosphorylation are all required for efficient mitochondrial clearance. These findings establish a direct pathway that integrates Ulk1- and Atg13-directed mitophagy with the stress response coordinated by Hsp90 and Cdc37.
C1 [Joo, Joung Hyuck; Joshi, Aashish; Hennessy-Walters, Kristin M.; McCastlain, Kelly; Iyengar, Rekha; Kundu, Mondira] St Jude Childrens Hosp, Dept Pathol, Memphis, TN 38105 USA.
[Zhang, Ji; Ney, Paul A.] St Jude Childrens Hosp, Dept Biochem, Memphis, TN 38105 USA.
[Dorsey, Frank C.; Rose, Kristie L.; Steeves, Meredith A.; Prater, Stephanie M.; Cleveland, John L.] Scripps Res Inst Florida, Dept Canc Biol, Jupiter, FL 33458 USA.
[Jung, Chang Hwa; Kim, Do-Hyung] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA.
[Suen, Der-Fen; Youle, Richard J.] NINDS, NIH, Bethesda, MD 20892 USA.
[Yang, Chia-Ying; Thompson, Craig B.] Univ Penn, Abramson Family Canc Res Inst, Dept Canc Biol, Sch Med, Philadelphia, PA 19104 USA.
RP Kundu, M (reprint author), St Jude Childrens Hosp, Dept Pathol, 332 N Lauderdale St, Memphis, TN 38105 USA.
EM mondira.kundu@stjude.org
OI Kim, Do-Hyung/0000-0002-2924-4370
FU National Institutes of Health [HL084199, CA123777, CA076379, DK074519,
GM097057, CA099179]; NINDS; Burroughs Welcome Fund; American Society of
Hematology; American Diabetes Association [ADA 7-07-CD-08]; monies from
the State of Florida; monies from the American Lebanese Syrian
Associated Charities (ALSAC)
FX We are grateful to Charles J. Sherr (St. Jude Children's Research
Hospital [SJCRH], Memphis, TN) for providing Cdc37 antibody; Emily
Tresse (SJCRH) for the LPC-mCherry-EGFP-LC3b construct; Toshifumi Tomoda
(Beckman Research Institute of City of Hope, Duarte, CA) for Flag-Ulk1
deletion constructs; Sharon Tooze (London Research Institute, Cancer
Research UK, London, UK) for providing an Atg13 antibody; Mark Hall (The
Scripps Research Institute [TSRI], Jupiter, Florida) for providing the
MSCV-Gateway-IRES-GFP vector; Reuben Shaw (The Salk Institute for
Biological Studies, La Jolla, CA) for providing ulk1-/- MEFs
stably expressing ulk2 shRNA; Jennifer Moore (SJCRH) for assistance with
generation of MEFs; Aaron Poole (SJCRH), Valerie Cavett (TSRI), Chunying
Yang (TSRI), and Laura Alsina (TSRI) for technical support; the
Proteomics Core facilities of Scripps Florida (TSRI) and the University
of Pennsylvania; the Biomedical Imaging Core facilities at SJCRH (Samuel
Connell, Jennifer Peters, and Sharon Erase) and University of
Pennsylvania (Neelima Shaw and Ray Meade); and Robert Matts (Oklahoma
State University) for helpful discussions. This research was partially
supported by grants from the National Institutes of Health to M.K.
(HL084199), F.C.D. (CA123777), J.L.C. (CA076379), P.A.N. (DK074519),
D.-H.K. (GM097057), and C.B.T. (CA099179); the NINDS intramural program
to R.Y; the Burroughs Welcome Fund to M.K.; the American Society of
Hematology to M.K.; and the American Diabetes Association to D.-H.K.
(ADA 7-07-CD-08); by monies from the State of Florida to J.L.C. at
Scripps Florida; and by monies from the American Lebanese Syrian
Associated Charities (ALSAC) to P.A.N. and M.K.
NR 59
TC 79
Z9 82
U1 3
U2 12
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD AUG 19
PY 2011
VL 43
IS 4
BP 572
EP 585
DI 10.1016/j.molcel.2011.06.018
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 810TW
UT WOS:000294151000010
PM 21855797
ER
PT J
AU Acuna-Soto, R
Viboud, C
Chowell, G
AF Acuna-Soto, Rodolfo
Viboud, Cecile
Chowell, Gerardo
TI Influenza and Pneumonia Mortality in 66 Large Cities in the United
States in Years Surrounding the 1918 Pandemic
SO PLOS ONE
LA English
DT Article
ID INCREASED SUSCEPTIBILITY; PNEUMOCOCCAL SURFACE; BACTERIAL PNEUMONIA;
SPANISH INFLUENZA; EPIDEMIC; WAVE; SUPERINFECTION; INFECTION; PATTERNS;
IMPACT
AB The 1918 influenza pandemic was a major epidemiological event of the twentieth century resulting in at least twenty million deaths worldwide; however, despite its historical, epidemiological, and biological relevance, it remains poorly understood. Here we examine the relationship between annual pneumonia and influenza death rates in the pre-pandemic (1910-17) and pandemic (1918-20) periods and the scaling of mortality with latitude, longitude and population size, using data from 66 large cities of the United States. The mean pre-pandemic pneumonia death rates were highly associated with pneumonia death rates during the pandemic period (Spearman rho = 0.64-0.72; P < 0.001). By contrast, there was a weak correlation between pre-pandemic and pandemic influenza mortality rates. Pneumonia mortality rates partially explained influenza mortality rates in 1918 (rho = 0.34, P = 0.005) but not during any other year. Pneumonia death counts followed a linear relationship with population size in all study years, suggesting that pneumonia death rates were homogeneous across the range of population sizes studied. By contrast, influenza death counts followed a power law relationship with a scaling exponent of similar to 0.81 (95% CI: 0.71, 0.91) in 1918, suggesting that smaller cities experienced worst outcomes during the pandemic. A linear relationship was observed for all other years. Our study suggests that mortality associated with the 1918-20 influenza pandemic was in part predetermined by pre-pandemic pneumonia death rates in 66 large US cities, perhaps through the impact of the physical and social structure of each city. Smaller cities suffered a disproportionately high per capita influenza mortality burden than larger ones in 1918, while city size did not affect pneumonia mortality rates in the pre-pandemic and pandemic periods.
C1 [Acuna-Soto, Rodolfo] Univ Nacl Autonoma Mexico, Fac Med, Dept Microbiol & Parasitol, Mexico City 04510, DF, Mexico.
[Viboud, Cecile; Chowell, Gerardo] NIH, Div Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Chowell, Gerardo] Arizona State Univ, Sch Human Evolut & Social Change, Computat & Modeling Sci Ctr, Tempe, AZ USA.
RP Acuna-Soto, R (reprint author), Univ Nacl Autonoma Mexico, Fac Med, Dept Microbiol & Parasitol, Mexico City 04510, DF, Mexico.
EM acunasoto.rodolfo@gmail.com
RI Chowell, Gerardo/F-5038-2012
OI Chowell, Gerardo/0000-0003-2194-2251
NR 31
TC 5
Z9 5
U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 19
PY 2011
VL 6
IS 8
AR e23467
DI 10.1371/journal.pone.0023467
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 810LZ
UT WOS:000294128100014
PM 21886792
ER
PT J
AU Zimmerberg, J
Hess, ST
AF Zimmerberg, Joshua
Hess, Samuel T.
TI Elongated Membrane Zones Boost Interactions of Diffusing Proteins
SO CELL
LA English
DT Editorial Material
C1 [Zimmerberg, Joshua] Eunice Kennedy Schriver Natl Inst Child Hlth & Hu, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
[Hess, Samuel T.] Univ Maine, Dept Phys & Astron, Orono, ME 04469 USA.
RP Zimmerberg, J (reprint author), Eunice Kennedy Schriver Natl Inst Child Hlth & Hu, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
EM joshz@mail.nih.gov; sam.hess@umit.maine.edu
NR 8
TC 2
Z9 2
U1 0
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD AUG 19
PY 2011
VL 146
IS 4
BP 501
EP 503
DI 10.1016/j.cell.2011.08.003
PG 4
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 809HY
UT WOS:000294043600004
PM 21854976
ER
PT J
AU Voss, TC
Schiltz, RL
Sung, MH
Yen, PM
Stamatoyannopoulos, JA
Biddie, SC
Johnson, TA
Miranda, TB
John, S
Hager, GL
AF Voss, Ty C.
Schiltz, R. Louis
Sung, Myong-Hee
Yen, Paul M.
Stamatoyannopoulos, John A.
Biddie, Simon C.
Johnson, Thomas A.
Miranda, Tina B.
John, Sam
Hager, Gordon L.
TI Dynamic Exchange at Regulatory Elements during Chromatin Remodeling
Underlies Assisted Loading Mechanism
SO CELL
LA English
DT Article
ID TRANSCRIPTION-FACTOR-BINDING; PROTEIN-DNA INTERACTIONS; CHIP-SEQ DATA;
GLUCOCORTICOID-RECEPTOR; IN-VIVO; LIVING CELLS; ESTROGEN-RECEPTOR;
GENE-EXPRESSION; SITES; ASSOCIATION
AB The glucocorticoid receptor (GR), like other eukaryotic transcription factors, regulates gene expression by interacting with chromatinized DNA response elements. Photobleaching experiments in living cells indicate that receptors transiently interact with DNA on the time scale of seconds and predict that the response elements may be sparsely occupied on average. Here, we show that the binding of one receptor at the glucocorticoid response element (GRE) does not reduce the steady-state binding of another receptor variant to the same GRE. Mathematical simulations reproduce this noncompetitive state using short GR/GRE residency times and relatively long times between DNA binding events. At many genomic sites where GR binding causes increased chromatin accessibility, concurrent steady-state binding levels for the variant receptor are actually increased, a phenomenon termed assisted loading. Temporally sparse transcription factor-DNA interactions induce local chromatin reorganization, resulting in transient access for binding of secondary regulatory factors.
C1 [Voss, Ty C.; Schiltz, R. Louis; Sung, Myong-Hee; Biddie, Simon C.; Johnson, Thomas A.; Miranda, Tina B.; John, Sam; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
[Yen, Paul M.] Duke Natl Univ Singapore, Cardiovasc & Metab Disorders Program, Lab Hormonal Regulat, Singapore 169857, Singapore.
[Stamatoyannopoulos, John A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
RP Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bldg 41,B602,41 Lib Dr, Bethesda, MD 20892 USA.
EM hagerg@exchange.nih.gov
OI Biddie, Simon/0000-0002-8253-0253
FU NIH, National Cancer Institute, Center for Cancer Research; D.O.D.'s
U.S. [W81XWH-06-1-0776]
FX The authors thank Anindya Indrawan for general technical support of
these experiments. Tatiana Karpova, manager of the NCI Fluorescence
Imaging Core Facility), provided expert assistance for epifluorescence
microscopy experiments. The resources of the NCI High-Throughput Imaging
Facility (HiTIF) were also essential for the rapid completion of this
study. This research was supported by the Intramural Research Program of
the NIH, National Cancer Institute, Center for Cancer Research, and by
the D.O.D.'s U.S. Congressionally Directed Medical Research Programs
Grant W81XWH-06-1-0776.
NR 38
TC 122
Z9 122
U1 1
U2 9
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD AUG 19
PY 2011
VL 146
IS 4
BP 544
EP 554
DI 10.1016/j.cell.2011.07.006
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 809HY
UT WOS:000294043600010
PM 21835447
ER
PT J
AU Lee, B
Park, I
Jin, S
Choi, H
Kwon, JT
Kim, J
Jeong, J
Cho, BN
Eddy, EM
Cho, C
AF Lee, Boyeon
Park, Inju
Jin, Sora
Choi, Heejin
Kwon, Jun Tae
Kim, Jihye
Jeong, Juri
Cho, Byung-Nam
Eddy, Edward M.
Cho, Chunghee
TI Impaired Spermatogenesis and Fertility in Mice Carrying a Mutation in
the Spink2 Gene Expressed Predominantly in Testes
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID SERINE-PROTEASE INHIBITOR; PANCREATIC ACINAR-CELLS; TRYPSIN-INHIBITOR;
MATRIX METALLOPROTEINASES; NETHERTON-SYNDROME; MOLECULAR-CLONING;
AMINO-ACID; HUSI-II; KAZAL; APOPTOSIS
AB Spermatogenesis is a complex process involving an intrinsic genetic program composed of germ cell-specific and -predominant genes. In this study, we investigated the mouse Spink2 (serine protease inhibitor Kazal-type 2) gene, which belongs to the SPINK family of proteins characterized by the presence of a Kazal-type serine protease inhibitor-pancreatic secretory trypsin inhibitor domain. We showed that recombinant mouse SPINK2 has trypsin-inhibitory activity. Distribution analyses revealed that Spink2 is transcribed strongly in the testis and weakly in the epididymis, but is not detected in other mouse tissues. Expression of Spink2 is specific to germ cells in the testis and is first evident at the pachytene spermatocyte stage. Immunoblot analyses demonstrated that SPINK2 protein is present in male germ cells at all developmental stages, including in testicular spermatogenic cells, testicular sperm, and mature sperm. To elucidate the functional role of SPINK2 in vivo, we generated mutant mice with diminished levels of SPINK2 using a gene trap mutagenesis approach. Mutant male mice exhibit significantly impaired fertility; further phenotypic analyses revealed that testicular integrity is disrupted, resulting in a reduction in sperm number. Moreover, we found that testes from mutant mice exhibit abnormal spermatogenesis and germ cell apoptosis accompanied by elevated serine protease activity. Our studies thus provide the first demonstration that SPINK2 is required for maintaining normal spermatogenesis and potentially regulates serine protease-mediated apoptosis in male germ cells.
C1 [Lee, Boyeon; Park, Inju; Jin, Sora; Choi, Heejin; Kwon, Jun Tae; Kim, Jihye; Jeong, Juri; Cho, Chunghee] Gwangju Inst Sci & Technol, Sch Life Sci, Kwangju 500712, South Korea.
[Cho, Byung-Nam] Catholic Univ Korea, Dept Sci, Puchon 420743, South Korea.
[Eddy, Edward M.] NIEHS, Gamete Biol Sect, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA.
RP Cho, C (reprint author), Gwangju Inst Sci & Technol, Sch Life Sci, Kwangju 500712, South Korea.
EM choch@gist.ac.kr
FU Korea Science and Engineering Foundation [2010-0028776]; Korea Research
Foundation [KRF-2008-313-C00736]; Gwangju Institute of Science and
Technology Systems Biology Infrastructure Establishment
FX This work was supported by Korea Science and Engineering Foundation
Grant 2010-0028776, a Korea Research Foundation Grant
KRF-2008-313-C00736, and a Gwangju Institute of Science and Technology
Systems Biology Infrastructure Establishment Grant.
NR 36
TC 12
Z9 14
U1 0
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 19
PY 2011
VL 286
IS 33
BP 29108
EP 29117
DI 10.1074/jbc.M111.244905
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 806TY
UT WOS:000293837000047
PM 21705336
ER
PT J
AU Van Duyne, R
Guendel, I
Narayanan, A
Gregg, E
Shafagati, N
Tyagi, M
Easley, R
Klase, Z
Nekhai, S
Kehn-Hall, K
Kashanchi, F
AF Van Duyne, Rachel
Guendel, Irene
Narayanan, Aarthi
Gregg, Edward
Shafagati, Nazly
Tyagi, Mudit
Easley, Rebecca
Klase, Zachary
Nekhai, Sergei
Kehn-Hall, Kylene
Kashanchi, Fatah
TI Varying Modulation of HIV-1 LTR Activity by BAF Complexes
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE chromatin remodeling; retrovirus; infection; phosphorylation;
transcription
ID CHROMATIN-REMODELING COMPLEX; TAT-ACTIVATED TRANSCRIPTION; ACTIN-RELATED
PROTEIN; ESSENTIAL COFACTOR; P-TEFB; I TAT; C-MYC; PHOSPHORYLATION;
IDENTIFICATION; TRANSFORMATION
AB The human immunodeficiency virus type 1 (HIV-1) long terminal repeat is present on both ends of the integrated viral genome and contains regulatory elements needed for transcriptional initiation and elongation. Post-integration, a highly ordered chromatin structure consisting of at least five nucleosomes, is found at the 5' long terminal repeat, the location and modification state of which control the state of active viral replication as well as silencing of the latent HIV-1 provirus. In this context, the chromatin remodeling field rapidly emerges as having a critical role in the control of viral gene expression. In the current study, we focused on unique Baf subunits that are common to the most highly recognized of chromatin remodeling proteins, the SWI/SNF (switching-defective-sucrose non-fermenting) complexes. We find that at least two Baf proteins, Baf53 and Baf170, are highly regulated in HIV-1-infected cells. Previously, studies have shown that the depletion of Baf53 in uninfected cells leads to the expansion of chromosomal territories and the decompaction of the chromatin. Baf53, in the presence of HIV-1 infection, co-elutes off of a chromatographic column as a different-sized complex when compared to uninfected cells and appears to be predominantly phosphorylated. The innate function of Baf53-containing complexes appears to be transcriptionally suppressive, in that knocking down Baf53 increases viral gene expression from cells both transiently and chronically infected with HIV-1. Additionally, cdk9/cyclin T in the presence of Tat is able to phosphorylate Baf53 in vitro, implying that this posttranslationally modified form relieves the suppressive effect and allows for viral transcription to proceed. (c) 2011 Elsevier Ltd. All rights reserved.
C1 [Van Duyne, Rachel; Guendel, Irene; Narayanan, Aarthi; Gregg, Edward; Shafagati, Nazly; Tyagi, Mudit; Easley, Rebecca; Kehn-Hall, Kylene; Kashanchi, Fatah] George Mason Univ, Natl Ctr Biodef & Infect Dis, Dept Mol & Microbiol, Manassas, VA 20110 USA.
[Van Duyne, Rachel; Kashanchi, Fatah] George Washington Univ, Med Ctr, Dept Microbiol Immunol & Trop Med, Washington, DC 20037 USA.
[Klase, Zachary] NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Nekhai, Sergei] Howard Univ, Dept Microbiol, Dept Med, Ctr Sickle Cell Dis, Washington, DC 20060 USA.
RP Kashanchi, F (reprint author), George Mason Univ, Natl Ctr Biodef & Infect Dis, Dept Mol & Microbiol, Discovery Hall,Room 306,10900 Univ Blvd,MS 1H8, Manassas, VA 20110 USA.
EM fkashanc@gmu.edu
RI Kehn-Hall, Kylene/I-5752-2013
FU National Institutes of Health [AI078859, AI074410, AI043894]
FX We would like to thank the members of the Kashanchi laboratory for
experiments and assistance with the manuscript. Also, we are grateful to
Dr. Lee Ratner for the HTLV-1 infectious clone and Dr. David Price for
the generous gift of cdk9/cyclin T and cdk9/cyclin T and Tat. Most of
the data on the manuscript were generated using funds from National
Institutes of Health grants AI078859, AI074410, and AI043894. R.V.D. is
a predoctoral student in the Microbiology and Immunology Program of the
Institute for Biomedical Sciences at the George Washington University.
NR 38
TC 17
Z9 17
U1 0
U2 1
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD AUG 19
PY 2011
VL 411
IS 3
BP 581
EP 596
DI 10.1016/j.jmb.2011.06.001
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 807YI
UT WOS:000293938500007
PM 21699904
ER
PT J
AU Zhao, HY
Brown, PH
Magone, MT
Schuck, P
AF Zhao, Huaying
Brown, Patrick H.
Magone, M. Teresa
Schuck, Peter
TI The Molecular Refractive Function of Lens gamma-Crystallins
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE crystallin; protein structure function; protein refractive index;
excluded volume
ID GLUTATHIONE-S-TRANSFERASE; VERTEBRATE EYE LENS; SPORE COAT PROTEIN;
X-RAY-ANALYSIS; STRUCTURAL PROTEIN; ALPHA-CRYSTALLIN; OCTOPUS LENS;
AMINO-ACIDS; LACTATE-DEHYDROGENASE; GENE RECRUITMENT
AB gamma-Crystallins constitute the major protein component in the nucleus of the vertebrate eye lens. Present at very high concentrations, they exhibit extreme solubility and thermodynamic stability to prevent scattering of light and formation of cataracts. However, functions beyond this structural role have remained mostly unclear. Here, we calculate molecular refractive index increments of crystallins. We show that all lens gamma-crystallins have evolved a significantly elevated molecular refractive index increment, which is far above those of most proteins, including nonlens members of the beta gamma-crystallin family from different species. The same trait has evolved in parallel in crystallins of different phyla, including S-crystallins of cephalopods. A high refractive index increment can lower the crystallin concentration required to achieve a suitable refractive power of the lens and thereby reduce their propensity to aggregate and form cataracts. To produce a significant increase in the refractive index increment, a substantial global shift in amino acid composition is required, which can naturally explain the highly unusual amino acid composition of gamma-crystallins and their functional homologues. This function provides a new perspective for interpreting their molecular structure. (c) 2011 Published by Elsevier Ltd.
C1 [Zhao, Huaying; Magone, M. Teresa; Schuck, Peter] NIH, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, Bethesda, MD 20892 USA.
[Brown, Patrick H.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA.
RP Schuck, P (reprint author), NIH, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, Bldg 13,Room 3N17,13 South Dr, Bethesda, MD 20892 USA.
EM schuckp@mail.nih.gov
RI Zhao, Huaying/F-5716-2012;
OI Schuck, Peter/0000-0002-8859-6966
FU National Institute of Biomedical Imaging and Bioengineering, National
Institutes of Health
FX We thank Dr. Cu-Gang Chang for providing the coordinates from the
homology model of octopus S-crystallin, Dr. Andor Kiss for providing
some protein sequences, and Dr. Graeme Wistow for critically reading an
initial draft of the manuscript. This work was supported by the
Intramural Research Program of the National Institute of Biomedical
Imaging and Bioengineering, National Institutes of Health.
NR 126
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U1 2
U2 31
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD AUG 19
PY 2011
VL 411
IS 3
BP 680
EP 699
DI 10.1016/j.jmb.2011.06.007
PG 20
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 807YI
UT WOS:000293938500013
PM 21684289
ER
PT J
AU Tabak, LA
Collins, FS
AF Tabak, Lawrence A.
Collins, Francis S.
TI Weaving a Richer Tapestry in Biomedical Science
SO SCIENCE
LA English
DT Editorial Material
C1 [Tabak, Lawrence A.; Collins, Francis S.] NIH, Bethesda, MD 20892 USA.
RP Tabak, LA (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM tabakl@mail.nih.gov; colllinsf@mail.nih.gov
FU Intramural NIH HHS [Z99 OD999999]
NR 12
TC 28
Z9 29
U1 0
U2 5
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD AUG 19
PY 2011
VL 333
IS 6045
BP 940
EP 941
DI 10.1126/science.1211704
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 808TD
UT WOS:000294000400030
PM 21852476
ER
PT J
AU Metcalf, CJE
Graham, AL
Huijben, S
Barclay, VC
Long, GH
Grenfell, BT
Read, AF
Bjornstad, ON
AF Metcalf, C. J. E.
Graham, A. L.
Huijben, S.
Barclay, V. C.
Long, G. H.
Grenfell, B. T.
Read, A. F.
Bjornstad, O. N.
TI Partitioning Regulatory Mechanisms of Within-Host Malaria Dynamics Using
the Effective Propagation Number
SO SCIENCE
LA English
DT Article
ID BLOOD-STAGE MALARIA; PLASMODIUM-CHABAUDI; IMMUNE-RESPONSES; PARASITES;
INFECTIONS; MODEL; ALPHA(+)-THALASSEMIA; COMPETITION; CHILDREN; ANEMIA
AB Immune clearance and resource limitation (via red blood cell depletion) shape the peaks and troughs of malaria parasitemia, which in turn affect disease severity and transmission. Quantitatively partitioning the relative roles of these effects through time is challenging. Using data from rodent malaria, we estimated the effective propagation number, which reflects the relative importance of contrasting within-host control mechanisms through time and is sensitive to the inoculating parasite dose. Our analysis showed that the capacity of innate responses to restrict initial parasite growth saturates with parasite dose and that experimentally enhanced innate immunity can affect parasite density indirectly via resource depletion. Such a statistical approach offers a tool to improve targeting of drugs or vaccines for human therapy by revealing the dynamics and interactions of within-host regulatory mechanisms.
C1 [Metcalf, C. J. E.] Univ Oxford, Dept Zool, Oxford OX1 3PS, England.
[Graham, A. L.; Grenfell, B. T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
[Huijben, S.; Barclay, V. C.; Read, A. F.; Bjornstad, O. N.] Penn State Univ, Ctr Infect Dis Dynam, State Coll, PA USA.
[Long, G. H.] Univ Sheffield, Dept Anim & Plant Sci, Western Bank, Sheffield S10 2TN, S Yorkshire, England.
[Grenfell, B. T.; Read, A. F.; Bjornstad, O. N.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Metcalf, CJE (reprint author), Univ Oxford, Dept Zool, S Parks Rd, Oxford OX1 3PS, England.
EM charlotte.metcalf@zoo.ox.ac.uk
RI Graham, Andrea/A-8808-2010; Long, Grainne/B-3635-2012; Bjornstad,
Ottar/I-4518-2012
OI Graham, Andrea/0000-0002-6580-2755; Long, Grainne/0000-0001-5080-9885;
FU Wellcome Trust; Darwin Trust of the University of Edinburgh; UK
Biotechnology and Biological Sciences Research Council; National
Institute of General Medical Sciences [R01GM089932]
FX Our empirical work was funded by the Wellcome Trust (A.F.R., V.C.B.,
G.H.L.), the Darwin Trust of the University of Edinburgh (S.H.), and the
UK Biotechnology and Biological Sciences Research Council (A.L.G.,
G.H.L.), and the theoretical work by the Bill and Melinda Gates
Foundation (C.J.E.M., B.T.G., O.N.B.), the RAPIDD program of the Science
and Technology Directorate (B.T.G., A.L.G., A.F.R.), and National
Institute of General Medical Sciences grant R01GM089932 (B.G., O.N.B.,
A.F.R.). We thank N. Mideo and P. Klepac for extensive discussion. All
authors discussed the results and implications and commented on the
manuscript at all stages. C.J.E.M. and O.N.B. developed the statistical
approach; A.F.R., V.B., and S.H. designed and performed the
dose-dependent and CD4+ T cell-depleted mice experiments;
A.L.G. and G.H.L. designed and performed the innate immunity
experiments. The authors declare no competing interests.
NR 43
TC 36
Z9 36
U1 6
U2 28
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD AUG 19
PY 2011
VL 333
IS 6045
BP 984
EP 988
DI 10.1126/science.1204588
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 808TD
UT WOS:000294000400047
PM 21852493
ER
PT J
AU Ginther, DK
Schaffer, WT
Schnell, J
Masimore, B
Liu, FY
Haak, LL
Kington, R
AF Ginther, Donna K.
Schaffer, Walter T.
Schnell, Joshua
Masimore, Beth
Liu, Faye
Haak, Laurel L.
Kington, Raynard
TI Race, Ethnicity, and NIH Research Awards
SO SCIENCE
LA English
DT Article
AB We investigated the association between a U. S. National Institutes of Health (NIH) R01 applicant's self-identified race or ethnicity and the probability of receiving an award by using data from the NIH IMPAC II grant database, the Thomson Reuters Web of Science, and other sources. Although proposals with strong priority scores were equally likely to be funded regardless of race, we find that Asians are 4 percentage points and black or African-American applicants are 13 percentage points less likely to receive NIH investigator-initiated research funding compared with whites. After controlling for the applicant's educational background, country of origin, training, previous research awards, publication record, and employer characteristics, we find that black applicants remain 10 percentage points less likely than whites to be awarded NIH research funding. Our results suggest some leverage points for policy intervention.
C1 [Ginther, Donna K.] Univ Kansas, Inst Policy & Social Res, Dept Econ, Lawrence, KS 66045 USA.
[Ginther, Donna K.] Univ Kansas, Inst Policy & Social Res, Ctr Sci Technol & Econ Policy, Lawrence, KS 66045 USA.
[Schaffer, Walter T.; Kington, Raynard] NIH, Bethesda, MD 20892 USA.
[Schnell, Joshua; Masimore, Beth; Liu, Faye; Haak, Laurel L.] Thomson Reuters, Discovery Log, Rockville, MD 20850 USA.
RP Ginther, DK (reprint author), Univ Kansas, Inst Policy & Social Res, Dept Econ, Lawrence, KS 66045 USA.
EM dginther@ku.edu
RI Schaffer, Walter/E-5982-2010; Haak, Laurel/C-4986-2008; Schnell,
Joshua/J-4000-2012; Ginther, Donna/F-7317-2016
OI Schaffer, Walter/0000-0002-2276-4656; Haak, Laurel/0000-0001-5109-3700;
Schnell, Joshua/0000-0001-9241-7441; Ginther, Donna/0000-0002-0881-7969
FU NSF [SES-0353703]; NIH [1R01AG36820-01, HHSN276200800458U,
HHSN276200900100U, 07-6008 OD OER]
FX D.K.G. acknowledges financial support from NSF grant SES-0353703 and NIH
grant 1R01AG36820-01. D. K. G. and Discovery Logic, a Thomson Reuters
company, acknowledge support from NIH contracts HHSN276200800458U and
HHSN276200900100U, made possible through an NIH Evaluation Set-Aside
Award to W. T. S. (07-6008 OD OER). We thank C. Bollinger, S. Kahn, and
W. McGarvey for helpful discussions. The analytical files used in the
studies described here contain personal information from individuals who
have submitted applications and in some cases have received awards from
NIH. Many of these application records have been matched to records
included in the Survey of Earned Doctorates as maintained by the
National Science Foundation and to records included in the Faculty
Roster maintained by the Association of American Medical Colleges. The
information is therefore protected by the Privacy Act of 1974 as amended
(5 U. S. C. 552a) and the National Science Foundation Act of 1950 as
amended (42 U. S. C. 1873(i). More complete information can be found in
the NSF/SRS Restricted-Use Data Procedures Guide available at
www.nsf.gov/statistics/license/forms/pdf/srs_license_guide_august_2008.p
df and the NSF Data and Tools Web site at
www.nsf.gov/statistics/database.cfm. Researchers interested in access
should call W. T. S. at 301-402-2725 to discuss the security clearance
requirements necessary for using the data. A de-identified version of
the data files will be posted at
http://report.nih.gov/investigators_and_trainees/index.aspx and archived
by Science.
NR 9
TC 123
Z9 123
U1 3
U2 42
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD AUG 19
PY 2011
VL 333
IS 6045
BP 1015
EP 1019
DI 10.1126/science.1196783
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 808TD
UT WOS:000294000400055
PM 21852498
ER
PT J
AU Solomon, DA
Kim, T
Diaz-Martinez, LA
Fair, J
Elkahloun, AG
Harris, BT
Toretsky, JA
Rosenberg, SA
Shukla, N
Ladanyi, M
Samuels, Y
James, CD
Yu, HT
Kim, JS
Waldman, T
AF Solomon, David A.
Kim, Taeyeon
Diaz-Martinez, Laura A.
Fair, Joshlean
Elkahloun, Abdel G.
Harris, Brent T.
Toretsky, Jeffrey A.
Rosenberg, Steven A.
Shukla, Neerav
Ladanyi, Marc
Samuels, Yardena
James, C. David
Yu, Hongtao
Kim, Jung-Sik
Waldman, Todd
TI Mutational Inactivation of STAG2 Causes Aneuploidy in Human Cancer
SO SCIENCE
LA English
DT Article
ID TUMOR-SUPPRESSOR GENE; GLIOBLASTOMA-MULTIFORME; CHROMOSOME INSTABILITY;
COPY NUMBER; COHESIN; HETEROZYGOSITY; TUMORIGENESIS; OVEREXPRESSION;
EXPRESSION; GENOMES
AB Most cancer cells are characterized by aneuploidy, an abnormal number of chromosomes. We have identified a clue to the mechanistic origins of aneuploidy through integrative genomic analyses of human tumors. A diverse range of tumor types were found to harbor deletions or inactivating mutations of STAG2, a gene encoding a subunit of the cohesin complex, which regulates the separation of sister chromatids during cell division. Because STAG2 is on the X chromosome, its inactivation requires only a single mutational event. Studying a near-diploid human cell line with a stable karyotype, we found that targeted inactivation of STAG2 led to chromatid cohesion defects and aneuploidy, whereas in two aneuploid human glioblastoma cell lines, targeted correction of the endogenous mutant alleles of STAG2 led to enhanced chromosomal stability. Thus, genetic disruption of cohesin is a cause of aneuploidy in human cancer.
C1 [Solomon, David A.; Kim, Taeyeon; Fair, Joshlean; Toretsky, Jeffrey A.; Kim, Jung-Sik; Waldman, Todd] Georgetown Univ, Sch Med, Dept Oncol, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA.
[Diaz-Martinez, Laura A.; Yu, Hongtao] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA.
[Diaz-Martinez, Laura A.; Yu, Hongtao] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA.
[Elkahloun, Abdel G.; Samuels, Yardena] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
[Harris, Brent T.] Georgetown Univ, Sch Med, Dept Neurol, Washington, DC 20057 USA.
[Harris, Brent T.] Georgetown Univ, Sch Med, Dept Pathol, Washington, DC 20057 USA.
[Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Shukla, Neerav; Ladanyi, Marc] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA.
[James, C. David] Univ Calif San Francisco, Helen Diller Comprehens Canc Ctr, Brain Tumor Res Ctr, Dept Neurol Surg, San Francisco, CA 94143 USA.
RP Waldman, T (reprint author), Georgetown Univ, Sch Med, Dept Oncol, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA.
EM waldmant@georgetown.edu
RI James, Charles/E-2721-2012;
OI James, Charles/0000-0002-1027-203X; Diaz-Martinez,
Laura/0000-0002-7226-7068
FU NIH [R01CA115699, R21CA143282]; SPORE grant [CA097257]; American Cancer
Society [RSG0619101]; National Human Genome Research Institute, NIH
FX We thank K. Creswell, S. Sen, and Applied Genetics Laboratories for
technical assistance; and M. White and the Brain Tumor Tissue Bank of
Canada, S. Baker, F. Bunz, J.-M. Peters, and the Children's Oncology
Group for reagents and tumor samples. This research was supported by NIH
grants R01CA115699 (T. W.), R21CA143282 (T. W.), SPORE grant CA097257
(C.D.J.), and American Cancer Society grant RSG0619101 (T. W.).
Georgetown University has filed a patent application relating to the
application of the mutations described in this work to the diagnosis and
treatment of cancer. Y.S. is supported by the Intramural Research
Programs of the National Human Genome Research Institute, NIH. Primer
sequences are in table S6. For copy number arrays: the scanned array
images and processed data sets have been deposited in the Gene
Expression Omnibus (www.ncbi.nlm.nih.gov/geo, dataset GSE13021). For
expression microarrays: the scanned array images and processed data sets
have been deposited in the Gene Expression Omnibus
(www.ncbi.nlm.nih.gov/geo, dataset GSE28214)
NR 25
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U1 2
U2 14
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD AUG 19
PY 2011
VL 333
IS 6045
BP 1039
EP 1043
DI 10.1126/science.1203619
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 808TD
UT WOS:000294000400062
PM 21852505
ER
PT J
AU Minor, RK
Baur, JA
Gomes, AP
Ward, TM
Csiszar, A
Mercken, EM
Abdelmohsen, K
Shin, YK
Canto, C
Scheibye-Knudsen, M
Krawczyk, M
Irusta, PM
Martin-Montalvo, A
Hubbard, BP
Zhang, YQ
Lehrmann, E
White, AA
Price, NL
Swindell, WR
Pearson, KJ
Becker, KG
Bohr, VA
Gorospe, M
Egan, JM
Talan, MI
Auwerx, J
Westphal, CH
Ellis, JL
Ungvari, Z
Vlasuk, GP
Elliott, PJ
Sinclair, DA
de Cabo, R
AF Minor, Robin K.
Baur, Joseph A.
Gomes, Ana P.
Ward, Theresa M.
Csiszar, Anna
Mercken, Evi M.
Abdelmohsen, Kotb
Shin, Yu-Kyong
Canto, Carles
Scheibye-Knudsen, Morten
Krawczyk, Melissa
Irusta, Pablo M.
Martin-Montalvo, Alejandro
Hubbard, Basil P.
Zhang, Yongqing
Lehrmann, Elin
White, Alexa A.
Price, Nathan L.
Swindell, William R.
Pearson, Kevin J.
Becker, Kevin G.
Bohr, Vilhelm A.
Gorospe, Myriam
Egan, Josephine M.
Talan, Mark I.
Auwerx, Johan
Westphal, Christoph H.
Ellis, James L.
Ungvari, Zoltan
Vlasuk, George P.
Elliott, Peter J.
Sinclair, David A.
de Cabo, Rafael
TI SRT1720 improves survival and healthspan of obese mice
SO SCIENTIFIC REPORTS
LA English
DT Article
ID SMALL-MOLECULE ACTIVATORS; SIRT1 ACTIVATION; MITOCHONDRIAL BIOGENESIS;
LIFE-SPAN; CALORIE RESTRICTION; INSULIN SENSITIVITY; BILE-ACIDS;
RESVERATROL; PROTECTS; PGC-1-ALPHA
AB Sirt1 is an NAD1-dependent deacetylase that extends lifespan in lower organisms and improves metabolism and delays the onset of age-related diseases in mammals. Here we show that SRT1720, a synthetic compound that was identified for its ability to activate Sirt1 in vitro, extends both mean and maximum lifespan of adult mice fed a high-fat diet. This lifespan extension is accompanied by health benefits including reduced liver steatosis, increased insulin sensitivity, enhanced locomotor activity and normalization of gene expression profiles and markers of inflammation and apoptosis, all in the absence of any observable toxicity. Using a conditional SIRT1 knockout mouse and specific gene knockdowns we show SRT1720 affects mitochondrial respiration in a Sirt1- and PGC-1a-dependent manner. These findings indicate that SRT1720 has long-term benefits and demonstrate for the first time the feasibility of designing novel molecules that are safe and effective in promoting longevity and preventing multiple age-related diseases in mammals.
C1 [Minor, Robin K.; Ward, Theresa M.; Mercken, Evi M.; Irusta, Pablo M.; Martin-Montalvo, Alejandro; Pearson, Kevin J.; de Cabo, Rafael] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA.
[Baur, Joseph A.] Univ Penn, Sch Med, Dept Physiol, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA.
[Gomes, Ana P.; Hubbard, Basil P.; Price, Nathan L.; Sinclair, David A.] Harvard Univ, Sch Med, Dept Pathol, Paul F Glenn Labs Biol Mech Aging, Boston, MA 02115 USA.
[Csiszar, Anna; Ungvari, Zoltan] Univ Oklahoma, Hlth Sci Ctr, Dept Geriatr Med, Reynolds Oklahoma Ctr Aging, Oklahoma City, OK 73104 USA.
[Abdelmohsen, Kotb; Gorospe, Myriam] NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA.
[Shin, Yu-Kyong; White, Alexa A.; Egan, Josephine M.] NIA, Clin Invest Lab, NIH, Baltimore, MD 21224 USA.
[Canto, Carles; Auwerx, Johan] Ecole Polytech Fed Lausanne, LISP, CH-1015 Lausanne, Switzerland.
[Scheibye-Knudsen, Morten; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
[Krawczyk, Melissa; Talan, Mark I.] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA.
[Zhang, Yongqing; Lehrmann, Elin; Becker, Kevin G.] NIA, Gene Express & Genom Unit, NIH, Baltimore, MD 21224 USA.
[Irusta, Pablo M.] Georgetown Univ, Med Ctr, Dept Human Sci, Washington, DC 20007 USA.
[Swindell, William R.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Pearson, Kevin J.] Univ Kentucky, Grad Ctr Nutr Sci, Lexington, KY 40536 USA.
[Westphal, Christoph H.; Ellis, James L.; Vlasuk, George P.; Elliott, Peter J.] Sirtris, Cambridge, MA 02139 USA.
RP de Cabo, R (reprint author), NIA, Lab Expt Gerontol, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM decabora@mail.nih.gov
RI de Cabo, Rafael/J-5230-2016; Martin-Montalvo, Alejandro/C-2031-2017;
OI Canto, Carles/0000-0002-5167-7922; de Cabo, Rafael/0000-0002-3354-2442;
Martin-Montalvo, Alejandro/0000-0002-3886-5355; Lehrmann,
Elin/0000-0002-9869-9475; Baur, Joseph/0000-0001-8262-6549;
Scheibye-Knudsen, Morten/0000-0002-6637-1280; abdelmohsen,
Kotb/0000-0001-6240-5810; Becker, Kevin/0000-0002-6794-6656; Sinclair,
David/0000-0002-9936-436X; , rafael/0000-0003-2830-5693
FU NIH [R00AG031182]; NIA/NIH; Swiss National Science Foundation; ERC;
Glenn Foundation for Medical Research
FX This research was conducted under a Cooperative Research and Development
Agreement (CRADA) between Sirtris, a GSK Company, and the National
Institute on Aging, National Institutes of Health (NIA/NIH). Microarray
data are archived under the accession number GSE19102. JAB is supported
by NIH Pathway to Independence Award R00AG031182. We are grateful to
Dawn Nines, Dawn Phillips and Justine Lucas for their excellent animal
care. We also thank Larry Brant for help with data analyses and Olga
Carlson for technical assistance. Funding was provided by the Intramural
Research Program of the NIA/NIH, the Swiss National Science Foundation
and the ERC Ideas program. Funding to DAS was provided by the NIH/NIA
Extramural Research Program and the Glenn Foundation for Medical
Research.
NR 49
TC 91
Z9 94
U1 1
U2 20
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD AUG 18
PY 2011
VL 1
AR 70
DI 10.1038/srep00070
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 835QT
UT WOS:000296051600001
PM 22355589
ER
PT J
AU Crispino, G
Di Pasquale, G
Scimemi, P
Rodriguez, L
Ramirez, FG
De Siati, RD
Santarelli, RM
Arslan, E
Bortolozzi, M
Chiorini, JA
Mammano, F
AF Crispino, Giulia
Di Pasquale, Giovanni
Scimemi, Pietro
Rodriguez, Laura
Ramirez, Fabian Galindo
De Siati, Romolo Daniele
Santarelli, Rosa Maria
Arslan, Edoardo
Bortolozzi, Mario
Chiorini, John A.
Mammano, Fabio
TI BAAV Mediated GJB2 Gene Transfer Restores Gap Junction Coupling in
Cochlear Organotypic Cultures from Deaf Cx26Sox10Cre Mice
SO PLOS ONE
LA English
DT Article
ID BOVINE ADENOASSOCIATED VIRUS; MAMMALIAN INNER-EAR; CONNEXIN 26;
HEARING-LOSS; HEREDITARY DEAFNESS; DOMINANT DEAFNESS; STRIA VASCULARIS;
ATP RELEASE; NULL MICE; EXPRESSION
AB The deafness locus DFNB1 contains GJB2, the gene encoding connexin26 and GJB6, encoding connexin30, which appear to be coordinately regulated in the inner ear. In this work, we investigated the expression and function of connexin26 and connexin30 from postnatal day 5 to adult age in double transgenic Cx26(Sox10Cre) mice, which we obtained by crossing connexin26 floxed mice with a deleter Sox10-Cre line. Cx26(Sox10Cre) mice presented with complete connexin26 ablation in the epithelial gap junction network of the cochlea, whereas connexin30 expression was developmentally delayed; immunolabeling patterns for both connexins were normal in the cochlear lateral wall. In vivo electrophysiological measurements in Cx26(Sox10Cre) mice revealed profound hearing loss accompanied by reduction of endocochlear potential, and functional experiments performed in postnatal cochlear organotypic cultures showed impaired gap junction coupling. Transduction of these cultures with a bovine adeno associated virus vector restored connexin26 protein expression and rescued gap junction coupling. These results suggest that restoration of normal connexin levels by gene delivery via recombinant adeno associated virus could be a way to rescue hearing function in DFNB1 mouse models and, in future, lead to the development of therapeutic interventions in humans.
C1 [Crispino, Giulia; Rodriguez, Laura; Ramirez, Fabian Galindo; Bortolozzi, Mario; Mammano, Fabio] Ist Veneto Med Mol, Fdn Ric Biomed Avanzata, Padua, Italy.
[Crispino, Giulia; Rodriguez, Laura; Bortolozzi, Mario; Mammano, Fabio] Univ Padua, Dipartimento Fis G Galilei, Padua, Italy.
[Di Pasquale, Giovanni; Chiorini, John A.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA.
[Scimemi, Pietro; De Siati, Romolo Daniele; Santarelli, Rosa Maria; Arslan, Edoardo] Univ Padua, Dipartimento Specialita Med Chirurg, Padua, Italy.
[Scimemi, Pietro; De Siati, Romolo Daniele; Santarelli, Rosa Maria; Arslan, Edoardo] Univ Padua, Serv Audiol, Padua, Italy.
[Bortolozzi, Mario; Mammano, Fabio] Ist CNR Neurosci, Padua, Italy.
RP Crispino, G (reprint author), Ist Veneto Med Mol, Fdn Ric Biomed Avanzata, Padua, Italy.
EM fabio.mammano@unipd.it
RI Mammano, Fabio/I-5064-2012; Bortolozzi, Mario/H-6872-2015;
OI Mammano, Fabio/0000-0003-3751-1691; Bortolozzi,
Mario/0000-0001-7198-9838; SCIMEMI, PIETRO/0000-0001-5273-1938
FU European Commission [LSHGCT20054512063]; Fondazione Cariparo; Telethon
Italy [GGP09137]; Italian Ministry of Research [2007BZ4RX3_003]
FX Supported by grants to FM from: The European Commission [FP6 Integrated
Project EuroHear, grant number LSHGCT20054512063]; Fondazione Cariparo
[Progetti di Eccellenza 2006-2007], Telethon Italy [grant number
GGP09137], Italian Ministry of Research [PRIN 2007, grant number
2007BZ4RX3_003]. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 50
TC 17
Z9 18
U1 3
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 18
PY 2011
VL 6
IS 8
AR e23279
DI 10.1371/journal.pone.0023279
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 810LN
UT WOS:000294126900016
PM 21876744
ER
PT J
AU Lindhurst, MJ
Sapp, JC
Teer, JK
Johnston, JJ
Finn, EM
Peters, K
Turner, J
Cannons, JL
Bick, D
Blakemore, L
Blumhorst, C
Brockmann, K
Calder, P
Cherman, N
Deardorff, MA
Everman, DB
Golas, G
Greenstein, RM
Kato, BM
Keppler-Noreuil, KM
Kuznetsov, SA
Miyamoto, RT
Newman, K
Ng, D
O'Brien, K
Rothenberg, S
Schwartzentruber, DJ
Singhal, V
Tirabosco, R
Upton, J
Wientroub, S
Zackai, EH
Hoag, K
Whitewood-Neal, T
Robey, PG
Schwartzberg, PL
Darling, TN
Tosi, LL
Mullikin, JC
Biesecker, LG
AF Lindhurst, Marjorie J.
Sapp, Julie C.
Teer, Jamie K.
Johnston, Jennifer J.
Finn, Erin M.
Peters, Kathryn
Turner, Joyce
Cannons, Jennifer L.
Bick, David
Blakemore, Laurel
Blumhorst, Catherine
Brockmann, Knut
Calder, Peter
Cherman, Natasha
Deardorff, Matthew A.
Everman, David B.
Golas, Gretchen
Greenstein, Robert M.
Kato, B. Maya
Keppler-Noreuil, Kim M.
Kuznetsov, Sergei A.
Miyamoto, Richard T.
Newman, Kurt
Ng, David
O'Brien, Kevin
Rothenberg, Steven
Schwartzentruber, Douglas J.
Singhal, Virender
Tirabosco, Roberto
Upton, Joseph
Wientroub, Shlomo
Zackai, Elaine H.
Hoag, Kimberly
Whitewood-Neal, Tracey
Robey, Pamela G.
Schwartzberg, Pamela L.
Darling, Thomas N.
Tosi, Laura L.
Mullikin, James C.
Biesecker, Leslie G.
TI A Mosaic Activating Mutation in AKT1 Associated with the Proteus
Syndrome
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID MCCUNE-ALBRIGHT SYNDROME; TUMOR-SUPPRESSOR PTEN; GERMLINE MUTATION;
LETHAL GENES; MICE; CELLS; LIPOMATOSIS; CHALLENGES; DEFECTS; GROWTH
AB BACKGROUND
The Proteus syndrome is characterized by the overgrowth of skin, connective tissue, brain, and other tissues. It has been hypothesized that the syndrome is caused by somatic mosaicism for a mutation that is lethal in the nonmosaic state.
METHODS
We performed exome sequencing of DNA from biopsy samples obtained from patients with the Proteus syndrome and compared the resultant DNA sequences with those of unaffected tissues obtained from the same patients. We confirmed and extended an observed association, using a custom restriction-enzyme assay to analyze the DNA in 158 samples from 29 patients with the Proteus syndrome. We then assayed activation of the AKT protein in affected tissues, using phosphorylation-specific antibodies on Western blots.
RESULTS
Of 29 patients with the Proteus syndrome, 26 had a somatic activating mutation (c.49G -> A, p.Glu17Lys) in the oncogene AKT1, encoding the AKT1 kinase, an enzyme known to mediate processes such as cell proliferation and apoptosis. Tissues and cell lines from patients with the Proteus syndrome harbored admixtures of mutant alleles that ranged from 1% to approximately 50%. Mutant cell lines showed greater AKT phosphorylation than did control cell lines. A pair of single-cell clones that were established from the same starting culture and differed with respect to their mutation status had different levels of AKT phosphorylation.
CONCLUSIONS
The Proteus syndrome is caused by a somatic activating mutation in AKT1, proving the hypothesis of somatic mosaicism and implicating activation of the PI3K-AKT pathway in the characteristic clinical findings of overgrowth and tumor susceptibility in this disorder. (Funded by the Intramural Research Program of the National Human Genome Research Institute.)
C1 [Biesecker, Leslie G.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Cherman, Natasha; Kuznetsov, Sergei A.; Robey, Pamela G.] Natl Inst Dent & Craniofacial Res, Bethesda, MD USA.
[Schwartzentruber, Douglas J.] NCI, Bethesda, MD 20892 USA.
[Darling, Thomas N.] Uniformed Serv Univ Hlth Sci, Dept Dermatol, Bethesda, MD 20814 USA.
[Mullikin, James C.; Biesecker, Leslie G.] Natl Inst Hlth Intramural Sequencing Ctr, Rockville, MD USA.
[Bick, David] Med Coll Wisconsin, Dept Pediat, Div Genet, Milwaukee, WI 53226 USA.
[Blakemore, Laurel; Tosi, Laura L.] Childrens Natl Med Ctr, Div Orthopaed & Sports Med, Washington, DC 20010 USA.
[Newman, Kurt] Childrens Natl Med Ctr, Dept Surg, Washington, DC 20010 USA.
[Brockmann, Knut] Univ Gottingen, Dept Pediat & Pediat Neurol, Gottingen, Germany.
[Calder, Peter; Tirabosco, Roberto] Royal Natl Orthopaed Hosp, Stanmore HA7 4LP, Middx, England.
[Deardorff, Matthew A.; Zackai, Elaine H.] Childrens Hosp Philadelphia, Div Genet, Philadelphia, PA 19104 USA.
[Everman, David B.] Greenwood Genet Ctr, Greenwood, SC 29646 USA.
[Greenstein, Robert M.] Univ Connecticut, Dept Genet & Dev Biol, Hartford, CT USA.
[Kato, B. Maya] Ear Inst, Palm Desert, CA USA.
[Keppler-Noreuil, Kim M.] Univ Iowa, Dept Pediat, Div Genet, Iowa City, IA 52242 USA.
[Miyamoto, Richard T.] Indiana Univ Purdue Univ, Dept Otolaryngol, Indianapolis, IN 46202 USA.
[Rothenberg, Steven] Rocky Mt Hosp Children, Dept Pediat Surg, Denver, CO USA.
[Singhal, Virender] Childrens Mercy Hosp & Clin, Dept Pediat Plast & Craniofacial Surg, Kansas City, MO USA.
[Upton, Joseph] Childrens Hosp, Div Plast Surg, Boston, MA 02115 USA.
[Wientroub, Shlomo] Tel Aviv Univ, Tel Aviv Med Ctr, Dana Childrens Hosp, Dept Pediat Orthopaed, IL-69978 Tel Aviv, Israel.
[Hoag, Kimberly] Proteus Syndrome Fdn, Colorado Springs, CO USA.
[Whitewood-Neal, Tracey] Proteus Syndrome Fdn UK, Bexhill On Sea, England.
RP Biesecker, LG (reprint author), NHGRI, Genet Dis Res Branch, NIH, Bldg 49,Rm 4A56, Bethesda, MD 20892 USA.
EM leslieb@helix.nih.gov
RI Robey, Pamela/H-1429-2011;
OI Robey, Pamela/0000-0002-5316-5576; Darling, Thomas/0000-0002-5161-1974
FU National Human Genome Research Institute; Proteus Syndrome Foundation in
the United States; Proteus Syndrome Foundation in the United Kingdom
FX Supported by the Intramural Research Program of the National Human
Genome Research Institute. The Proteus Syndrome Foundations in the
United States and the United Kingdom contributed financial support for
the sequencing.
NR 35
TC 296
Z9 305
U1 2
U2 22
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD AUG 18
PY 2011
VL 365
IS 7
BP 611
EP 619
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 808ER
UT WOS:000293960500008
PM 21793738
ER
PT J
AU Weiss, SA
Bassett, DS
Rubinstein, D
Holroyd, T
Apud, J
Dickinson, D
Coppola, R
AF Weiss, Shennan Aibel
Bassett, Danielle S.
Rubinstein, Daniel
Holroyd, Tom
Apud, Jose
Dickinson, Dwight
Coppola, Richard
TI Functional brain network characterization and adaptivity during task
practice in healthy volunteers and people with schizophrenia
SO FRONTIERS IN HUMAN NEUROSCIENCE
LA English
DT Article
DE cognitive remediation; schizophrenia; magnetoencephalography; graph
theory; synthetic aperture magnetometry; practice; beta band; high gamma
ID SMALL-WORLD NETWORKS; COGNITIVE REMEDIATION; PITCH MEMORY; CORTICAL
PLASTICITY; AUDITORY-STIMULI; CONTROLLED-TRIAL; WORKING-MEMORY;
GAMMA-BAND; EEG DATA; CORTEX
AB Cognitive remediation involves task practice and may improve deficits in people suffering from schizophrenia, but little is known about underlying neurophysiological mechanisms. In people with schizophrenia and controls, we used magnetoencephalography (MEG) to examine accuracy and practice-related changes in parameters indexing neural network structure and activity, to determine whether these might be useful assays of the efficacy of cognitive remediation. Two MEG recordings were acquired during performance of a tone discrimination task used to improve the acuity of auditory processing, before and after similar to 2.5 h of task practice. Accuracy before practice was negatively correlated with beta-band cost efficiency, a graph theoretical measure of network organization. Synthetic aperture magnetometry was used to localize brain oscillations with high spatial accuracy; results demonstrated sound and sensorimotor modulations of the beta band in temporo-parietal regions and the sensorimotor cortex respectively. High-gamma activity also correlated with sensorimotor processing during the task, with activation of auditory regions following sound stimulation, and activation of the left sensorimotor cortex preceding the button press. High-gamma power in the left frontal cortex was also found to correlate with accuracy. Following practice, sound-induced broad-band power in the left angular gyri increased. Accuracy improved and was found to correlate with increased mutual information (MI) between sensors in temporal-parietal regions in the beta band but not global cost efficiency. Based on these results, we conclude that hours of task practice can induce meso-scale changes such as increased power in relevant brain regions as well as changes in MI that correlate with improved accuracy.
C1 [Weiss, Shennan Aibel] Columbia Univ, Dept Neurol, New York, NY 10027 USA.
[Bassett, Danielle S.] Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA.
[Rubinstein, Daniel; Holroyd, Tom] NIMH, MEG Core Facil, Bethesda, MD 20892 USA.
[Apud, Jose; Dickinson, Dwight; Coppola, Richard] NIMH, Clin Brain Disorder Branch, Bethesda, MD 20892 USA.
RP Weiss, SA (reprint author), Columbia Univ, Dept Neurol, New York, NY 10027 USA.
EM saw2164@columbia.edu
FU NIMH
FX This research was supported by the Intramural Research Program of the
NIMH.
NR 61
TC 6
Z9 7
U1 2
U2 11
PU FRONTIERS RES FOUND
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-5161
J9 FRONT HUM NEUROSCI
JI Front. Hum. Neurosci.
PD AUG 17
PY 2011
VL 5
AR 81
DI 10.3389/fnhum.2011.00081
PG 14
WC Neurosciences; Psychology
SC Neurosciences & Neurology; Psychology
GA 814QO
UT WOS:000294472200001
PM 21887140
ER
PT J
AU Cortini, R
Kornyshev, AA
Lee, DJ
Leikin, S
AF Cortini, Ruggero
Kornyshev, Alexei A.
Lee, Dominic J.
Leikin, Sergey
TI Electrostatic Braiding and Homologous Pairing of DNA Double Helices
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID COLI TOPOISOMERASE-IV; SUPERCOILED DNA; SINGLE-MOLECULE; II
TOPOISOMERASES; FORCES; AGGREGATION; RECOMBINATION; SIMULATIONS;
STABILITY; MECHANISM
AB Homologous pairing and braiding (supercoiling) have crucial effects on genome organization, maintenance, and evolution. Generally, the pairing and braiding processes are discussed in different contexts, independently of each other. However, analysis of electrostatic interactions between DNA double helices suggests that in some situations these processes may be related. Here we present a theory of DNA braiding that accounts for the elastic energy of DNA double helices as well as for the chiral nature of the discrete helical patterns of DNA charges. This theory shows that DNA braiding may be affected, stabilized, or even driven by chiral electrostatic interactions. For example, electrostatically driven braiding may explain the surprising recent observation of stable pairing of homologous double-stranded DNA in solutions containing only monovalent salt. Electrostatic stabilization of left-handed braids may stand behind the chiral selectivity of type II topoisomerases and positive plasmid supercoiling in hyperthermophilic bacteria and archea.
C1 [Cortini, Ruggero; Kornyshev, Alexei A.; Lee, Dominic J.] Univ London Imperial Coll Sci Technol & Med, Dept Chem, London SW7 2AY, England.
[Leikin, Sergey] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Phys Biochem, NIH, Bethesda, MD USA.
RP Cortini, R (reprint author), Univ London Imperial Coll Sci Technol & Med, Dept Chem, London SW7 2AY, England.
EM ruggero.cortini@gmail.com; a.kornyshev@imperial.ac.uk;
domolee@hotmail.com; leikins@mail.nih.gov
RI Leikin, Sergey/A-5518-2008
OI Leikin, Sergey/0000-0001-7095-0739
FU United Kingdom Engineering and Physical Sciences Research Council
[EP/H004319/1]; Human Frontiers Science Program [RGP0049/2010-C102];
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health
FX This work was supported by the United Kingdom Engineering and Physical
Sciences Research Council (grant No. EP/H004319/1), the Human Frontiers
Science Program (grant No. RGP0049/2010-C102), and the Intramural
research program of The Eunice Kennedy Shriver National Institute of
Child Health and Human Development, National Institutes of Health.
NR 55
TC 17
Z9 18
U1 2
U2 19
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
J9 BIOPHYS J
JI Biophys. J.
PD AUG 17
PY 2011
VL 101
IS 4
BP 875
EP 884
DI 10.1016/j.bpj.2011.06.058
PG 10
WC Biophysics
SC Biophysics
GA 810CS
UT WOS:000294103600017
PM 21843478
ER
PT J
AU Piknova, B
Kocharyan, A
Schechter, AN
Silva, AC
AF Piknova, Barbora
Kocharyan, Ara
Schechter, Alan N.
Silva, Afonso C.
TI The role of nitrite in neurovascular coupling
SO BRAIN RESEARCH
LA English
DT Article
DE Cerebral blood flow; Functional hyperemia; Nitrite; Nitric oxide;
Neurovascular coupling; nNOS inhibition
ID CEREBRAL-BLOOD-FLOW; OXIDE SYNTHASE; NORMAL BRAIN; STIMULATION; RAT;
HYPERCAPNIA; INHIBITION; HYPOXIA; DISEASE
AB Nitric oxide (NO), a potent vasodilator and nontraditional neurotransmitter, is an important mediator of the changes in cerebral blood flow (CBF) associated with increased neuronal activity (neurovascular coupling). In the present work, we investigated the role of NO and of its newly recognized precursor, nitrite, in neurovascular coupling using a well-established rat model of somatosensory stimulation. Biological synthesis of NO of neuronal origin was inhibited pharmacologically. Following the initial uncoupling of neuronal and hemodynamic responses to somatosensory stimulation, the NO donor sodium nitroprusside, added within the range of physiological concentrations, significantly increased, but did not fully restore the functional CBF response. In contrast, nitrite at its physiological concentration fully recovered neurovascular coupling to its original magnitude. The magnitude of the effect is, however, dose-dependent. Sub-physiological concentrations of nitrite were not enough to entirely restore neurovascular coupling and supra-physiological concentrations acted more as a local vasodilator that changed resting CBF and interfered with the functional CBF response. These results suggest that nitrite can be efficiently converted into NO and utilized to support normal cerebrovascular physiology. Published by Elsevier B.V.
C1 [Piknova, Barbora; Schechter, Alan N.] NIDDKD, NIH, Bethesda, MD 20892 USA.
[Kocharyan, Ara; Silva, Afonso C.] NINDS, NIH, Bethesda, MD 20892 USA.
RP Piknova, B (reprint author), NIDDKD, NIH, 9000 Rockville Pike,Bldg 10,Rm 9N318, Bethesda, MD 20892 USA.
EM piknovab@mail.nih.gov
OI Schechter, Alan N/0000-0002-5235-9408
FU NIH; NINDS; NIDDK
FX Authors would like to thank Xianfeng (Lisa) Zhang for her excellent
technical assistance. This research was supported by the Intramural
Research Program of the NIH, NINDS and NIDDK.
NR 31
TC 15
Z9 15
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
J9 BRAIN RES
JI Brain Res.
PD AUG 17
PY 2011
VL 1407
BP 62
EP 68
DI 10.1016/j.brainres.2011.06.045
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 810QO
UT WOS:000294142400006
PM 21764040
ER
PT J
AU Goldfeder, RL
Parker, SCJ
Ajay, SS
Abaan, HO
Margulies, EH
AF Goldfeder, Rachel L.
Parker, Stephen C. J.
Ajay, Subramanian S.
Abaan, Hatice Ozel
Margulies, Elliott H.
TI A Bioinformatics Approach for Determining Sample Identity from Different
Lanes of High-Throughput Sequencing Data
SO PLOS ONE
LA English
DT Article
ID MAP
AB The ability to generate whole genome data is rapidly becoming commoditized. For example, a mammalian sized genome (similar to 3Gb) can now be sequenced using approximately ten lanes on an Illumina HiSeq 2000. Since lanes from different runs are often combined, verifying that each lane in a genome's build is from the same sample is an important quality control. We sought to address this issue in a post hoc bioinformatic manner, instead of using upstream sample or "barcode" modifications. We rely on the inherent small differences between any two individuals to show that genotype concordance rates can be effectively used to test if any two lanes of HiSeq 2000 data are from the same sample. As proof of principle, we use recent data from three different human samples generated on this platform. We show that the distributions of concordance rates are non-overlapping when comparing lanes from the same sample versus lanes from different samples. Our method proves to be robust even when different numbers of reads are analyzed. Finally, we provide a straightforward method for determining the gender of any given sample. Our results suggest that examining the concordance of detected genotypes from lanes purported to be from the same sample is a relatively simple approach for confirming that combined lanes of data are of the same identity and quality.
C1 [Goldfeder, Rachel L.; Parker, Stephen C. J.; Ajay, Subramanian S.; Abaan, Hatice Ozel; Margulies, Elliott H.] NHGRI, Genome Informat Sect, Technol Branch, NIH, Bethesda, MD 20892 USA.
RP Goldfeder, RL (reprint author), NHGRI, Genome Informat Sect, Technol Branch, NIH, Bethesda, MD 20892 USA.
EM emargulies@illumina.com
FU National Human Genome Research Institute at the National Institutes of
Health, USA
FX This work was funded by the intramural research program of the National
Human Genome Research Institute at the National Institutes of Health,
USA. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 11
TC 2
Z9 2
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 17
PY 2011
VL 6
IS 8
AR e23683
DI 10.1371/journal.pone.0023683
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 810JJ
UT WOS:000294121300083
PM 21858207
ER
PT J
AU Lu, Y
Ji, YY
Ganesan, S
Schloesser, R
Martinowich, K
Sun, M
Mei, F
Chao, MV
Lu, B
AF Lu, Yuan
Ji, Yuanyuan
Ganesan, Sundar
Schloesser, Robert
Martinowich, Keri
Sun, Mu
Mei, Fan
Chao, Moses V.
Lu, Bai
TI TrkB as a Potential Synaptic and Behavioral Tag
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID LONG-TERM POTENTIATION; PROTEIN-SYNTHESIS; LATE-PHASE;
HIPPOCAMPAL-NEURONS; TYROSINE KINASE; MESSENGER-RNAS; RECEPTOR TRKB;
BDNF; PLASTICITY; LTP
AB Late-phase long-term potentiation (L-LTP), a cellular model for long-term memory (LTM), requires de novo protein synthesis. An attractive hypothesis for synapse specificity of long-term memory is "synaptic tagging": synaptic activity generates a tag, which "captures" the PRPs (plasticity-related proteins) derived outside of synapses. Here we provide evidence that TrkB, the receptor of BDNF (brain-derived neurotrophic factor), may serve as a "synaptic tag." TrkB is transiently activated by weak theta-burst stimulation (TBS) that induces only early-phase LTP (E-LTP). This TrkB activation is independent of protein synthesis, and confined to stimulated synapses. Induction of L-LTP by strong stimulation in one synaptic pathway converts weak TBS-induced E-LTP to L-LTP in a second, independent pathway. Transient inhibition of TrkB around the time of weak TBS to the second pathway diminished L-LTP in that pathway without affecting the first one. Behaviorally, weak training, which induces short-term memory (STM) but not LTM, can be consolidated into LTM by exposing animals to novel but not familiar environment 1 h before training. Inhibition of TrkB during STM training blocked such consolidation. These results suggest TrkB as a potential tag for synapse-specific expression of L-LTP and LTM.
C1 [Ji, Yuanyuan; Sun, Mu; Lu, Bai] GlaxoSmithKline Inc, R&D China, Shanghai 201203, Peoples R China.
[Lu, Yuan; Martinowich, Keri; Lu, Bai] NIMH, Gene Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA.
[Ji, Yuanyuan; Ganesan, Sundar; Mei, Fan; Lu, Bai] NICHD, Sect Neural Dev & Plast, NIH, Bethesda, MD 20892 USA.
[Schloesser, Robert; Martinowich, Keri] NIMH, Mood & Anxiety Program, NIH, Bethesda, MD 20892 USA.
[Chao, Moses V.] NYU Med Ctr, Skirball Inst, New York, NY 10016 USA.
RP Lu, B (reprint author), GlaxoSmithKline Inc, R&D China, Bldg 3,898 Halei Rd,Zhangjiang Hitech Pk, Shanghai 201203, Peoples R China.
EM bai.b.lu@gsk.com
RI Lu, Bai/A-4018-2012; Mei, Fan/H-2665-2012; Sun, Mu/A-6772-2008;
Martinowich, Keri/F-9841-2012;
OI Sun, Mu/0000-0001-8261-3705; Martinowich, Keri/0000-0002-5237-0789;
Chao, Moses/0000-0002-6969-3744
FU NIMH; NICHD; GSK RD China
FX This work was supported by the Intramural Research Programs of NIMH and
NICHD and by GSK R&D China. We thank Dr. David D. Ginty for providing
the TrkBF616A knock-in mice. We also thank Drs. Kimberly M.
Christian and KuanHong Wang for critical comments and constructive
suggestions for this manuscript, and Shiyi Jin for assistance with the
confocal microscopy.
NR 43
TC 45
Z9 45
U1 0
U2 11
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD AUG 17
PY 2011
VL 31
IS 33
BP 11762
EP 11771
DI 10.1523/JNEUROSCI.2707-11.2011
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 808CB
UT WOS:000293950300004
PM 21849537
ER
PT J
AU Cheng, K
Bai, L
Belluscio, L
AF Cheng, Kai
Bai, Li
Belluscio, Leonardo
TI Fas-Associated Factor 1 as a Regulator of Olfactory Axon Guidance
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID PROTEIN GAMMA-SUBUNIT; PARKINSONS-DISEASE; CASPASE ACTIVATION; SENSORY
NEURONS; MARKER PROTEIN; APOPTOSIS; SYSTEM; MOUSE; FAF1; MAP
AB Axon guidance is a crucial part of neural circuit formation. While precise axonal targeting forms the basis of accurate information delivery, the mechanisms that regulate this process are still unclear. Apoptotic signaling molecules have been identified in the axon terminal, but their specific role in axon guidance is not well understood. Here we use the mouse olfactory system as an in vivo model to demonstrate that by modulating Fas-associated factor 1 (FAF1), an apoptosis regulatory molecule, we can rewire axonal projections. Interestingly, FAF1 is highly expressed in the developing mouse olfactory system, but its expression is downregulated postnatally. Using a tetracycline-inducible promoter Tet-Off system, we generated transgenic mice in which FAF1 is specifically expressed in immature olfactory sensory neurons (OSNs) and show that overexpression of FAF1 not only misroutes OSN axons to deep layers of the olfactory bulb but also leads to widespread disruption of the glomerular layer. In addition, we also demonstrate that the specific convergence of P2 receptor OSN axons is completely distorted in the FAF1 mice. Strikingly, all of the mutant phenotypes can be recovered by shutting down FAF1 expression through the administration of doxycycline. Together, our study provides clear in vivo evidence that an apoptotic molecule can indeed regulate axon targeting and that OSNs can restore their organization even after broad disruption.
C1 [Belluscio, Leonardo] Natl Inst Neurol Disorders & Stroke, Dev Neural Plast Unit, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Belluscio, L (reprint author), Natl Inst Neurol Disorders & Stroke, Dev Neural Plast Unit, Porter Neurosci Res Ctr, NIH, Bldg 35,Room 3A-116,35 Convent Dr,MSC 3703, Bethesda, MD 20892 USA.
EM belluscl@ninds.nih.gov
FU National Institutes of Health [1ZIANS003116-01]
FX This work was supported by the National Institutes of Health, Intramural
Research Program, Project 1ZIANS003116-01. We thank the Ryba laboratory
for their generosity with transgenic lines, James Pickel at the National
Institute of Mental Health Transgenic Facility for pronuclear injection
and generation of TetO-FAF1 mice, and members of the Belluscio
laboratory for helpful comments on the manuscript.
NR 41
TC 5
Z9 6
U1 0
U2 3
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD AUG 17
PY 2011
VL 31
IS 33
BP 11905
EP 11913
DI 10.1523/JNEUROSCI.0053-11.2011
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 808CB
UT WOS:000293950300018
PM 21849551
ER
PT J
AU Freedman, ND
Silverman, DT
Hollenbeck, AR
Schatzkin, A
Abnet, CC
AF Freedman, Neal D.
Silverman, Debra T.
Hollenbeck, Albert R.
Schatzkin, Arthur
Abnet, Christian C.
TI Association Between Smoking and Risk of Bladder Cancer Among Men and
Women
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID ACTIVE CIGARETTE-SMOKING; HONOLULU HEART PROGRAM; LUNG-CANCER;
UNITED-STATES; REPRODUCTIVE FACTORS; PROSPECTIVE COHORT;
PANCREATIC-CANCER; ADVENTIST HEALTH; HISTOLOGIC TYPE; POOLED ANALYSIS
AB Context Previous studies indicate that the population attributable risk (PAR) of bladder cancer for tobacco smoking is 50% to 65% in men and 20% to 30% in women and that current cigarette smoking triples bladder cancer risk relative to never smoking. During the last 30 years, incidence rates have remained stable in the United States in men (123.8 per 100 000 person-years to 142.2 per 100 000 person-years) and women (32.5 per 100 000 person-years to 33.2 per 100 000 person-years); however, changing smoking prevalence and cigarette composition warrant revisiting risk estimates for smoking and bladder cancer.
Objective To evaluate the association between tobacco smoking and bladder cancer.
Design, Setting, and Participants Men (n=281 394) and women (n=186 134) of the National Institutes of Health-AARP (NIH-AARP) Diet and Health Study cohort completed a lifestyle questionnaire and were followed up between October 25, 1995, and December 31, 2006. Previous prospective cohort studies of smoking and incident bladder cancer were identified by systematic review and relative risks were estimated from fixed-effects models with heterogeneity assessed by the I-2 statistic.
Main Outcome Measures Hazard ratios (HRs), PARs, and number needed to harm (NNH).
Results During 4 518 941 person-years of follow-up, incident bladder cancer occurred in 3896 men (144.0 per 100 000 person-years) and 627 women (34.5 per 100 000 person-years). Former smokers (119.8 per 100 000 person-years; HR, 2.22; 95% confidence interval [CI], 2.03-2.44; NNH, 1250) and current smokers (177.3 per 100 000 person-years; HR, 4.06; 95% CI, 3.66-4.50; NNH, 727) had higher risks of bladder cancer than never smokers (39.8 per 100 000 person-years). In contrast, the summary risk estimate for current smoking in 7 previous studies (initiated between 1963 and 1987) was 2.94 (95% CI, 2.45-3.54; I-2=0.0%). The PAR for ever smoking in our study was 0.50 (95% CI, 0.45-0.54) in men and 0.52 (95% CI, 0.45-0.59) in women.
Conclusion Compared with a pooled estimate of US data from cohorts initiated between 1963 and 1987, relative risks for smoking in the more recent NIH-AARP Diet and Health Study cohort were higher, with PARs for women comparable with those for men.
C1 [Freedman, Neal D.; Silverman, Debra T.; Schatzkin, Arthur; Abnet, Christian C.] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Rockville, MD 20852 USA.
[Hollenbeck, Albert R.] AARP, Washington, DC USA.
RP Freedman, ND (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, 6120 Execut Blvd,EPS 320,MSC 7232, Rockville, MD 20852 USA.
EM freedmanne@mail.nih.gov
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 National Institutes of Health, National Cancer Institute, Division of
Cancer Epidemiology and Genetics; Florida Department of Health
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Division of
Cancer Epidemiology and Genetics. Cancer incidence data from Arizona
were collected by the Arizona Cancer Registry; from Georgia by the
Georgia Center for Cancer Statistics; from California by the California
Department of Health Services, Cancer Surveillance Section; from
Michigan by the Michigan Cancer Surveillance Program; from Florida by
the Florida Cancer Data System under contract to the Florida Department
of Health; from Louisiana by the Louisiana Tumor Registry; from New
Jersey by the New Jersey State Cancer Registry; from North Carolina by
the North Carolina Central Cancer Registry; from Pennsylvania by the
Division of Health Statistics and Research, Pennsylvania Department of
Health; and from Texas by the Texas Cancer Registry.
NR 57
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U1 2
U2 18
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD AUG 17
PY 2011
VL 306
IS 7
BP 737
EP 745
DI 10.1001/jama.2011.1142
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 807LP
UT WOS:000293900000023
PM 21846855
ER
PT J
AU Thomas, JD
Burke, TR
AF Thomas, Joshua D.
Burke, Terrence R., Jr.
TI Application of a water-soluble pyridyl disulfide amine linker for use in
Cu-free click bioconjugation
SO TETRAHEDRON LETTERS
LA English
DT Article
DE Bioconjugation; Cleavable linker; Cu-free click reaction; Pyridyl
disulfide
ID DELIVERY; GLUTATHIONE; PEPTIDE; CANCER; CELLS; LIGATION; CHAINS
AB Described herein is the design and synthesis of a discrete heterobifunctional PEG-based pyridyl disulfide/amine-containing linker that can be used in the Cu-free click preparation of bioconjugates. The title PEG-based pyridyl disulfide amine linker is a potentially useful reagent for preparing water-soluble disulfide-linked cargos, and that it may be particularly valuable in expanding the field of Cu-free click-based bioconjugations to include reductively labile antibody, polymer, or nanoparticle-based drug conjugates. Published by Elsevier Ltd.
C1 [Thomas, Joshua D.; Burke, Terrence R., Jr.] NCI, Biol Chem Lab, Mol Discovery Program, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
RP Burke, TR (reprint author), NCI, Biol Chem Lab, Mol Discovery Program, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
EM tburke@helix.nih.gov
RI Burke, Terrence/N-2601-2014
FU NIH, Center for Cancer Research, NCI-Frederick; National Cancer
Institute, National Institutes of Health
FX This work was supported in part by the Intramural Research Program of
the NIH, Center for Cancer Research, NCI-Frederick and the National
Cancer Institute, National Institutes of Health. 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 26
TC 5
Z9 5
U1 1
U2 21
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0040-4039
J9 TETRAHEDRON LETT
JI Tetrahedron Lett.
PD AUG 17
PY 2011
VL 52
IS 33
BP 4316
EP 4319
DI 10.1016/j.tetlet.2011.06.042
PG 4
WC Chemistry, Organic
SC Chemistry
GA 801JX
UT WOS:000293436100019
PM 21826118
ER
PT J
AU Rao, JS
Kim, HW
Kellom, M
Greenstein, D
Chen, M
Kraft, AD
Harry, GJ
Rapoport, SI
Basselin, M
AF Rao, Jagadeesh Sridhara
Kim, Hyung-Wook
Kellom, Matthew
Greenstein, Dede
Chen, Mei
Kraft, Andrew David
Harry, Gaylia Jean
Rapoport, Stanley Isaac
Basselin, Mireille
TI Increased neuroinflammatory and arachidonic acid cascade markers, and
reduced synaptic proteins, in brain of HIV-1 transgenic rats
SO JOURNAL OF NEUROINFLAMMATION
LA English
DT Article
ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; CENTRAL-NERVOUS-SYSTEM; CYTOSOLIC
PHOSPHOLIPASE A(2); EXPRESSING TNF-ALPHA; NEURONAL CELL-DEATH;
ALZHEIMERS-DISEASE; NITRIC-OXIDE; NEUROCOGNITIVE IMPAIRMENT; COGNITIVE
IMPAIRMENT
AB Background: Cognitive impairment has been reported in human immune deficiency virus-1- (HIV-1-) infected patients as well as in HIV-1 transgenic (Tg) rats. This impairment has been linked to neuroinflammation, disturbed brain arachidonic acid (AA) metabolism, and synapto-dendritic injury. We recently reported upregulated brain AA metabolism in 7- to 9-month-old HIV-1 Tg rats. We hypothesized that these HIV-1 Tg rats also would show upregulated brain inflammatory and AA cascade markers and a deficit of synaptic proteins.
Methods: We measured protein and mRNA levels of markers of neuroinflammation and the AA cascade, as well as pro-apoptotic factors and synaptic proteins, in brains from 7- to 9-month-old HIV-1 Tg and control rats.
Results: Compared with control brain, HIV-1 Tg rat brain showed immunoreactivity to glycoprotein 120 and tat HIV-1 viral proteins, and significantly higher protein and mRNA levels of (1) the inflammatory cytokines interleukin-1 beta and tumor necrosis factor alpha, (2) the activated microglial/macrophage marker CD11b, (3) AA cascade enzymes: AA-selective Ca(2+)-dependent cytosolic phospholipase A(2) (cPLA(2))-IVA, secretory sPLA(2)-IIA, cyclooxygenase (COX)-2, membrane prostaglandin E(2) synthase, 5-lipoxygenase (LOX) and 15-LOX, cytochrome p450 epoxygenase, and (4) transcription factor NF-kappa Bp50 DNA binding activity. HIV-1 Tg rat brain also exhibited signs of cell injury, including significantly decreased levels of brain-derived neurotrophic factor (BDNF) and drebrin, a marker of post-synaptic excitatory dendritic spines. Expression of Ca(2+)-independent iPLA(2)-VIA and COX-1 was unchanged.
Conclusions: HIV-1 Tg rats show elevated brain markers of neuroinflammation and AA metabolism, with a deficit in several synaptic proteins. These changes are associated with viral proteins and may contribute to cognitive impairment. The HIV-1 Tg rat may be a useful model for understanding progression and treatment of cognitive impairment in HIV-1 patients.
C1 [Rao, Jagadeesh Sridhara; Kim, Hyung-Wook; Kellom, Matthew; Chen, Mei; Rapoport, Stanley Isaac; Basselin, Mireille] NIA, Brain Physiol & Metab Sect, Bethesda, MD 20892 USA.
[Greenstein, Dede] NIMH, NIH, Bethesda, MD 20892 USA.
[Kraft, Andrew David; Harry, Gaylia Jean] Natl Inst Environm Hlth Sci, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
RP Rao, JS (reprint author), NIA, Brain Physiol & Metab Sect, Bethesda, MD 20892 USA.
EM jrao@mail.nih.gov
FU National Institute on Aging; National Institute of Mental Health
National Institutes of Health, Bethesda, MD; National Institute of
Environmental Health Sciences, National Institutes of Health, Research
Triangle Park, NC
FX This research was entirely supported by the Intramural Research Programs
of the National Institute on Aging and the National Institute of Mental
Health National Institutes of Health, Bethesda, MD, and the National
Institute of Environmental Health Sciences, National Institutes of
Health, Research Triangle Park, NC. We thank the NIH Fellows Editorial
Board for editing the manuscript.
NR 80
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U1 2
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-2094
J9 J NEUROINFLAMM
JI J. Neuroinflamm.
PD AUG 16
PY 2011
VL 8
AR 101
DI 10.1186/1742-2094-8-101
PG 13
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 822MZ
UT WOS:000295053500001
PM 21846384
ER
PT J
AU Solomon, BD
AF Solomon, Benjamin D.
TI VACTERL/VATER Association
SO ORPHANET JOURNAL OF RARE DISEASES
LA English
DT Review
ID RESPIRATORY-CHAIN DEFICIENCY; GENOTYPE-PHENOTYPE CORRELATIONS; PRENATAL
SONOGRAPHIC DIAGNOSIS; MULTIPLE CONGENITAL-ANOMALIES; RIGHT PULMONARY
AGENESIS; PALLISTER-HALL-SYNDROME; TOWNES-BROCKS-SYNDROME; ACID
RECEPTORS RARS; HOLT-ORAM-SYNDROME; VATER-ASSOCIATION
AB VACTERL/VATER association is typically defined by the presence of at least three of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. In addition to these core component features, patients may also have other congenital anomalies. Although diagnostic criteria vary, the incidence is estimated at approximately 1 in 10,000 to 1 in 40,000 live-born infants. The condition is ascertained clinically by the presence of the above-mentioned malformations; importantly, there should be no clinical or laboratory-based evidence for the presence of one of the many similar conditions, as the differential diagnosis is relatively large. This differential diagnosis includes (but is not limited to) Baller-Gerold syndrome, CHARGE syndrome, Currarino syndrome, deletion 22q11.2 syndrome, Fanconi anemia, Feingold syndrome, Fryns syndrome, MURCS association, oculo-auriculo-vertebral syndrome, Opitz G/BBB syndrome, Pallister-Hall syndrome, Townes-Brocks syndrome, and VACTERL with hydrocephalus. Though there are hints regarding causation, the aetiology has been identified only in a small fraction of patients to date, likely due to factors such as a high degree of clinical and causal heterogeneity, the largely sporadic nature of the disorder, and the presence of many similar conditions. New genetic research methods offer promise that the causes of VACTERL association will be better defined in the relatively near future. Antenatal diagnosis can be challenging, as certain component features can be difficult to ascertain prior to birth. The management of patients with VACTERL/VATER association typically centers around surgical correction of the specific congenital anomalies (typically anal atresia, certain types of cardiac malformations, and/or tracheo-esophageal fistula) in the immediate postnatal period, followed by long-term medical management of sequelae of the congenital malformations. If optimal surgical correction is achievable, the prognosis can be relatively positive, though some patients will continue to be affected by their congenital malformations throughout life. Importantly, patients with VACTERL association do not tend to have neurocognitive impairment.
C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Solomon, BD (reprint author), NHGRI, Med Genet Branch, NIH, Bldg 35,Room 1B-207, Bethesda, MD 20892 USA.
EM solomonb@mail.nih.gov
FU Division of Intramural Research, National Human Genome Research
Institute, National Institutes of Health and Human Services, United
States of America
FX This work was supported by the Division of Intramural Research, National
Human Genome Research Institute, National Institutes of Health and Human
Services, United States of America. The author would like to thank Dr.
Maximilian Muenke for his support and mentorship, and would like to
extend his deepest gratitude to the patients and families who have
participated in research on VACTERL association.
NR 114
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U1 0
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1750-1172
J9 ORPHANET J RARE DIS
JI Orphanet J. Rare Dis.
PD AUG 16
PY 2011
VL 6
AR 56
DI 10.1186/1750-1172-6-56
PG 12
WC Genetics & Heredity; Medicine, Research & Experimental
SC Genetics & Heredity; Research & Experimental Medicine
GA 817NC
UT WOS:000294679500001
PM 21846383
ER
PT J
AU Peluso, CE
Umulis, D
Kim, YJ
O'Connor, MB
Serpe, M
AF Peluso, Carolyn E.
Umulis, David
Kim, Young-Jun
O'Connor, Michael B.
Serpe, Mihaela
TI Shaping BMP Morphogen Gradients through Enzyme-Substrate Interactions
SO DEVELOPMENTAL CELL
LA English
DT Article
ID SHORT GASTRULATION GENE; DROSOPHILA EMBRYO; TWISTED GASTRULATION; SOG;
DPP; ANTAGONIST; PROTEINS; CHORDIN; TLD
AB Bone morphogenetic proteins (BMPs) regulate dorsal/ventral (D/V) patterning across the animal kingdom; however, the biochemical properties of certain pathway components can vary according to species-specific developmental requirements. For example, Tolloid (Tld)-like metalloproteases cleave vertebrate BMP-binding proteins called Chordins constitutively, while the Drosophila Chordin ortholog, Short gastrulation (Sog), is only cleaved efficiently when bound to BMPs. We identified Sog characteristics responsible for making its cleavage dependent on BMP binding. "Chordin-like" variants that are processed independently of BMPs changed the steep BM P gradient found in Drosophila embryos to a shallower profile, analogous to that observed in some vertebrate embryos. This change ultimately affected cell fate allocation and tissue size and resulted in increased variability of patterning. Thus, the acquisition of BMP-dependent Sog processing during evolution appears to facilitate long-range ligand diffusion and formation of a robust morphogen gradient, enabling the bistable BMP signaling outputs required for early Drosophila patterning.
C1 [Peluso, Carolyn E.; Kim, Young-Jun; Serpe, Mihaela] NICHD, Program Cellular Regulat & Metab, NIH, Bethesda, MD 20892 USA.
[Umulis, David] Purdue Univ, Dept Agr & Biol Engn, W Lafayette, IN 47907 USA.
[O'Connor, Michael B.] Univ Minnesota, Howard Hughes Med Inst, Minneapolis, MN 55455 USA.
[O'Connor, Michael B.] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA.
RP Serpe, M (reprint author), NICHD, Program Cellular Regulat & Metab, NIH, Bethesda, MD 20892 USA.
EM serpemih@mail.nih.gov
FU NIH; Showalter Trust
FX We thank Osamu Shimmi for communicating unpublished information and
Stuart Newfeld for comments on the manuscript. We thank Chi-Hon Lee and
Alan Hinnebusch for helpful discussions and suggestions. We are grateful
to Mary Jane Shimell for help in constructing the sog-HA transgene and
to Seth Blair for Sog antibodies. We thank Peter Nguyen, Gabriel Peal,
Jeremy Swan, and David Zhitomirsky for technical assistance. This work
was supported in part by the Intramural Research Program at NIH. D.U. is
supported by a grant from the Showalter Trust. M.B.O. is an Investigator
with the Howard Hughes Medical Institute.
NR 25
TC 20
Z9 20
U1 2
U2 10
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1534-5807
J9 DEV CELL
JI Dev. Cell
PD AUG 16
PY 2011
VL 21
IS 2
BP 375
EP 383
DI 10.1016/j.devcel.2011.06.025
PG 9
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 813RW
UT WOS:000294387300017
PM 21839924
ER
PT J
AU Lamb, JS
Chadwick, RS
AF Lamb, Jessica S.
Chadwick, Richard S.
TI Dual Traveling Waves in an Inner Ear Model with Two Degrees of Freedom
SO PHYSICAL REVIEW LETTERS
LA English
DT Article
ID TECTORIAL MEMBRANE; COCHLEAR MECHANICS; DISTORTION; GAIN; 2ND
AB We calculate traveling waves in the mammalian cochlea, which transduces acoustic vibrations into neural signals. We use a WKB-based mechanical model with both the tectorial membrane (TM) and basilar membrane (BM) coupled to the fluid to calculate motions along the length of the cochlea. This approach generates two wave numbers that manifest as traveling waves with different modes of motion between the BM and TM. The waves add differently on each mass, producing distinct tuning curves and different characteristic frequencies (CFs) for the TM and the BM. We discuss the effect of TM stiffness and coupling on the waves and tuning curves. We also consider how the differential motions between the masses could influence the cochlear amplifier and how mode conversion could take place in the cochlea.
C1 [Lamb, Jessica S.; Chadwick, Richard S.] NIDCD, Sect Auditory Mech, NIH, Bethesda, MD 20892 USA.
RP Lamb, JS (reprint author), NIDCD, Sect Auditory Mech, NIH, Bethesda, MD 20892 USA.
FU National Institute on Deafness and other Communication Disorders
[DC00033-15]
FX This work was supported by the intramural program project DC00033-15 in
the National Institute on Deafness and other Communication Disorders. We
thank E. Dimitriadis and S. Smith for critical comments, and A. Hoofring
for creating the illustration in Fig. 1(c).
NR 20
TC 23
Z9 23
U1 0
U2 10
PU AMER PHYSICAL SOC
PI COLLEGE PK
PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA
SN 0031-9007
J9 PHYS REV LETT
JI Phys. Rev. Lett.
PD AUG 16
PY 2011
VL 107
IS 8
AR 088101
DI 10.1103/PhysRevLett.107.088101
PG 4
WC Physics, Multidisciplinary
SC Physics
GA 807SW
UT WOS:000293921000026
PM 21929207
ER
PT J
AU Masedunskas, A
Sramkova, M
Parente, L
Sales, KU
Amornphimoltham, P
Bugge, TH
Weigert, R
AF Masedunskas, Andrius
Sramkova, Monika
Parente, Laura
Sales, Katiuchia Uzzun
Amornphimoltham, Panomwat
Bugge, Thomas H.
Weigert, Roberto
TI Role for the actomyosin complex in regulated exocytosis revealed by
intravital microscopy
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE in vivo imaging; cytoskeleton
ID PAROTID ACINAR-CELLS; SECRETORY GRANULES; FUSION PORE; MYOSIN-II;
COMPOUND EXOCYTOSIS; SALIVARY SECRETION; PROTEIN SECRETION; PANCREATIC
ACINI; EPITHELIAL-CELLS; PLASMA-MEMBRANE
AB The regulation and the dynamics of membrane trafficking events have been studied primarily in in vitro models that often do not fully reflect the functional complexity found in a living multicellular organism. Here we used intravital microscopy in the salivary glands of live rodents to investigate regulated exocytosis, a fundamental process in all of the secretory organs. We found that beta-adrenergic stimulation elicits exocytosis of large secretory granules, which gradually collapse with the apical plasma membrane without any evidence of compound exocytosis, as was previously described. Furthermore, we show that the driving force required to complete the collapse of the granules is provided by the recruitment of F-actin and nonmuscle myosin II on the granule membranes that is triggered upon fusion with the plasma membrane. Our results provide information on the machinery controlling regulated secretion and show that intravital microscopy provides unique opportunities to address fundamental questions in cell biology under physiological conditions.
C1 [Masedunskas, Andrius; Sramkova, Monika; Parente, Laura; Amornphimoltham, Panomwat; Weigert, Roberto] Natl Inst Dent & Craniofacial Res, Intracellular Membrane Trafficking Unit, NIH, Bethesda, MD 20892 USA.
[Sales, Katiuchia Uzzun; Bugge, Thomas H.] Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Sect, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
[Masedunskas, Andrius] Univ N Carolina, Dept Biol, Chapel Hill, NC 27514 USA.
RP Weigert, R (reprint author), Natl Inst Dent & Craniofacial Res, Intracellular Membrane Trafficking Unit, NIH, Bethesda, MD 20892 USA.
EM weigertr@mail.nih.gov
OI Masedunskas, Andrius/0000-0002-4533-5467
FU National Institutes of Health, National Institute of Dental and
Craniofacial Research
FX We thank Drs. J. S. Gutkind, J. Donaldson, P. Randazzo, and M. J. Danton
for critical reading of the manuscript. This research was supported by
the Intramural Research Program of the National Institutes of Health,
National Institute of Dental and Craniofacial Research.
NR 45
TC 45
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U1 0
U2 3
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD AUG 16
PY 2011
VL 108
IS 33
BP 13552
EP 13557
DI 10.1073/pnas.1016778108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 807KC
UT WOS:000293895100043
PM 21808006
ER
PT J
AU Carbone, M
Baris, YI
Bertino, P
Brass, B
Comertpay, S
Dogan, AU
Gaudino, G
Jube, S
Kanodia, S
Partridge, CR
Pass, HI
Rivera, ZS
Steele, I
Tuncer, M
Way, S
Yang, HN
Miller, A
AF Carbone, Michele
Baris, Y. Izzettin
Bertino, Pietro
Brass, Brian
Comertpay, Sabahattin
Dogan, A. Umran
Gaudino, Giovanni
Jube, Sandro
Kanodia, Shreya
Partridge, Charles R.
Pass, Harvey I.
Rivera, Zeyana S.
Steele, Ian
Tuncer, Murat
Way, Steven
Yang, Haining
Miller, Aubrey
TI Erionite exposure in North Dakota and Turkish villages with mesothelioma
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE asbestosis; cancer; carcinogenesis; environmental carcinogenesis;
mineral fiber carcinogenesis
ID MALIGNANT PLEURAL MESOTHELIOMA; ASBESTOS; TURKEY; CELLS; TRANSFORMATION;
VERMICULITE; CONTACTS; MONTANA; ZEOLITE; WORKERS
AB Exposure to erionite, an asbestos-like mineral, causes unprecedented rates of malignant mesothelioma (MM) mortality in some Turkish villages. Erionite deposits are present in at least 12 US states. We investigated whether increased urban development has led to erionite exposure in the United States and after preliminary exploration, focused our studies on Dunn County, North Dakota (ND). In Dunn County, ND, we discovered that over the past three decades, more than 300 miles of roads were surfaced with erionite-containing gravel. To determine potential health implications, we compared erionite from the Turkish villages to that from ND. Our study evaluated airborne point exposure concentrations, examined the physical and chemical properties of erionite, and examined the hallmarks of mesothelial cell transformation in vitro and in vivo. Airborne erionite concentrations measured in ND along roadsides, indoors, and inside vehicles, including school buses, equaled or exceeded concentrations in Boyali, where 6.25% of all deaths are caused by MM. With the exception of outdoor samples along roadsides, ND concentrations were lower than those measured in Turkish villages with MM mortality ranging from 20 to 50%. The physical and chemical properties of erionite from Turkey and ND are very similar and they showed identical biological activities. Considering the known 30- to 60-y latency for MM development, there is reason for concern for increased risk in ND in the future. Our findings indicate that implementation of novel preventive and early detection programs in ND and other erionite-rich areas of the United States, similar to efforts currently being undertaken in Turkey, is warranted.
C1 [Carbone, Michele; Bertino, Pietro; Comertpay, Sabahattin; Gaudino, Giovanni; Jube, Sandro; Kanodia, Shreya; Rivera, Zeyana S.; Yang, Haining] Univ Hawaii, Ctr Canc, Honolulu, HI 96813 USA.
[Baris, Y. Izzettin; Tuncer, Murat] Hacettepe Univ, TR-06500 Ankara, Turkey.
[Brass, Brian; Partridge, Charles R.; Way, Steven] US EPA, Denver, CO 80202 USA.
[Dogan, A. Umran] King Fahd Univ Petr & Minerals, Dept Earth Sci, Dhahran 31261, Saudi Arabia.
[Dogan, A. Umran] Univ Iowa, Dept Chem & Biochem Engn, Iowa City, IA 52242 USA.
[Pass, Harvey I.] NYU, Langone Med Ctr, New York, NY 10016 USA.
[Pass, Harvey I.] NYU, Ctr Canc, New York, NY 10016 USA.
[Rivera, Zeyana S.] Univ Hawaii, Dept Mol Biosci & Bioengn, Honolulu, HI 96813 USA.
[Steele, Ian] Univ Chicago, Dept Geophys Sci, Chicago, IL 60637 USA.
[Tuncer, Murat] Turkish Minist Hlth, TR-06434 Ankara, Turkey.
[Yang, Haining] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96813 USA.
[Miller, Aubrey] NIEHS, NIH, Bethesda, MD USA.
RP Carbone, M (reprint author), Univ Hawaii, Ctr Canc, Honolulu, HI 96813 USA.
EM mcarbone@cc.hawaii.edu
RI Dogan, Ahmet/B-4087-2010
FU National Cancer Institute at the National Institutes of Health [P01
114047]; American Association for Cancer Research; Butitta Mesothelioma
Foundation; Mesothelioma Applied Research Foundation; Riviera
Foundation; Aramec Foundation; Hawaii Community Foundation
FX This work was supported in part by the National Cancer Institute at the
National Institutes of Health (P01 114047 to M. C.), the American
Association for Cancer Research Landon Innovator Award, and a grant from
the Butitta Mesothelioma Foundation (to M. C.). This work was also
supported by grants from Mesothelioma Applied Research Foundation,
Riviera Foundation, Aramec Foundation (to H.Y.), and the Hawaii
Community Foundation (to H.Y. and G. G.). For B. B., C. R. P., S. W.
(USEPA), and A. M. (NIEHS), this research does not represent policies or
positions of the respective agencies.
NR 38
TC 61
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U1 1
U2 22
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD AUG 16
PY 2011
VL 108
IS 33
BP 13618
EP 13623
DI 10.1073/pnas.1105887108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 807KC
UT WOS:000293895100054
PM 21788493
ER
PT J
AU Sharma, D
Masison, DC
AF Sharma, Deepak
Masison, Daniel C.
TI Single methyl group determines prion propagation and protein degradation
activities of yeast heat shock protein (Hsp)-70 chaperones Ssa1p and
Ssa2p
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID SACCHAROMYCES-CEREVISIAE; CELL-GROWTH; IN-VITRO; HEAT-SHOCK-PROTEIN-70
FAMILY; GUANIDINE-HYDROCHLORIDE; FUNCTIONAL SPECIFICITY; MOLECULAR
CHAPERONES; CYTOSOLIC HSP70; TRANSGENIC MICE; URE3
AB Organisms encode multiple homologous heat shock protein (Hsp)-70s, which are essential protein chaperones that play the major role in cellular protein "quality control." Although Hsp70s are functionally redundant and highly homologous, many possess distinct functions. A regulatory motif underlying such distinctions, however, is unknown. The 98% identical cytoplasmic Hsp70s Ssa1p and Ssa2p function differently with regard to propagation of yeast [URE3] prions and in the vacuolar-mediated degradation of gluconeogenesis enzymes, such as FBPase. Here, we show that the Hsp70 nucleotide binding domain (NBD) regulates these functional specificities. We find little difference in ATPase, protein refolding, and amyloid inhibiting activities of purified Ssa1p and Ssa2p, but show that interchanging NBD residue alanine 83 (Ssa1p) and glycine 83 (Ssa2p) switched functions of Ssa1p and Ssa2p in [URE3] propagation and FBPase degradation. Disrupting the degradation pathway did not affect prion propagation, however, indicating these are two distinct processes where Ssa1/2p chaperones function differently. Our results suggest that the primary evolutionary pressure for Hsp70 functional distinctions is not to specify interactions of Hsp70 with substrate, but to specify the regulation of this activity. Our data suggest a rationale for maintaining multiple Hsp70s and suggest that subtle differences among Hsp70s evolved to provide functional specificity without affecting overall enzymatic activity.
C1 [Sharma, Deepak; Masison, Daniel C.] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
RP Masison, DC (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
EM masisond@helix.nih.gov
FU NIH, National Institute of Diabetes and Digestive and Kidney Diseases
FX We thank C. Randell Brown for antibodies and advice, R. Duden for
antibodies, R. Wickner for plamids, and our National Institutes of
Health (NIH) colleagues for insightful discussion and helpful comments
on the manuscript. This work was supported by the Intramural Research
Program of the NIH, National Institute of Diabetes and Digestive and
Kidney Diseases.
NR 39
TC 26
Z9 26
U1 1
U2 7
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD AUG 16
PY 2011
VL 108
IS 33
BP 13665
EP 13670
DI 10.1073/pnas.1107421108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 807KC
UT WOS:000293895100062
PM 21808014
ER
PT J
AU Harberts, E
Yao, K
Wohler, JE
Maric, D
Ohayon, J
Henkin, R
Jacobson, S
AF Harberts, Erin
Yao, Karen
Wohler, Jillian E.
Maric, Dragan
Ohayon, Joan
Henkin, Robert
Jacobson, Steven
TI Human herpesvirus-6 entry into the central nervous system through the
olfactory pathway
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE olfactory system; viral infection
ID POLYMERASE-CHAIN-REACTION; HERPES-SIMPLEX-VIRUS; LIMBIC ENCEPHALITIS;
CEREBROSPINAL-FLUID; MULTIPLE-SCLEROSIS; HUMAN ASTROCYTES; INFECTION;
HUMAN-HERPESVIRUS-6; BRAIN; CELLS
AB Viruses have been implicated in the development of neurodegenerative diseases, such as Alzheimer's, Parkinson's, and multiple sclerosis. Human herpesvirus-6 (HHV-6) is a neurotropic virus that has been associated with a wide variety of neurologic disorders, including encephalitis, mesial temporal lobe epilepsy, and multiple sclerosis. Currently, the route of HHV-6 entry into the CNS is unknown. Using autopsy specimens, we found that the frequency of HHV-6 DNA in the olfactory bulb/tract region was among the highest in the brain regions examined. Given this finding, we investigated whether HHV-6 may infect the CNS via the olfactory pathway. HHV-6 DNA was detected in a total of 52 of 126 (41.3%) nasal mucous samples, showing the nasal cavity is a reservoir for HHV-6. Furthermore, specialized olfactory-ensheathing glial cells located in the nasal cavity were demonstrated to support HHV-6 replication in vitro. Collectively, these results support HHV-6 utilization of the olfactory pathway as a route of entry into the CNS.
C1 [Harberts, Erin; Yao, Karen; Wohler, Jillian E.; Ohayon, Joan; Jacobson, Steven] NINDS, Viral Immunol Sect, Bethesda, MD 20892 USA.
[Yao, Karen] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA.
[Maric, Dragan] NINDS, Flow Cytometry Core Facil, Bethesda, MD 20892 USA.
[Henkin, Robert] Ctr Mol Nutr & Sensory Disorders, Washington, DC 20016 USA.
RP Jacobson, S (reprint author), NINDS, Viral Immunol Sect, Bethesda, MD 20892 USA.
EM jacobsons@ninds.nih.gov
NR 37
TC 31
Z9 32
U1 0
U2 5
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD AUG 16
PY 2011
VL 108
IS 33
BP 13734
EP 13739
DI 10.1073/pnas.1105143108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 807KC
UT WOS:000293895100074
PM 21825120
ER
PT J
AU Snitkin, ES
Zelazny, AM
Montero, CI
Stock, F
Mijares, L
Murray, PR
Segre, JA
AF Snitkin, Evan S.
Zelazny, Adrian M.
Montero, Clemente I.
Stock, Frida
Mijares, Lilia
Murray, Patrick R.
Segre, Julie A.
CA NISC Comparative Sequence Program
TI Genome-wide recombination drives diversification of epidemic strains of
Acinetobacter baumannii
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE bacterial evolution; microbial genomics; clinical microbiology; hospital
epidemiology; hospital infection
ID GRAM-NEGATIVE BACILLI; OUTBREAK; RESISTANCE; EVOLUTION; IDENTIFICATION;
INFECTIONS; HOSPITALS; SPREAD; GENES; CLONE
AB Acinetobacter baumannii is an emerging human pathogen and a significant cause of nosocomial infections among hospital patients worldwide. The enormous increase in multidrug resistance among hospital isolates and the recent emergence of pandrug-resistant strains underscores the urgency to understand how A. baumannii evolves in hospital environments. To this end, we undertook a genomic study of a polyclonal outbreak of multidrug-resistant A. baumannii at the research-based National Institutes of Health Clinical Center. Comparing the complete genome sequences of the three dominant outbreak strain types enabled us to conclude that, despite all belonging to the same epidemic lineage, the three strains diverged before their arrival at the National Institutes of Health. The simultaneous presence of three divergent strains from this lineage supports its increasing prevalence in international hospitals and suggests an ongoing adaptation to the hospital environment. Further genomic comparisons uncovered that much of the diversification that occurred since the divergence of the three outbreak strains was mediated by homologous recombination across 20% of their genomes. Inspection of recombinant regions revealed that several regions were associated with either the loss or swapping out of genes encoding proteins that are exposed to the cell surface or that synthesize cell-surface molecules. Extending our analysis to a larger set of international clinical isolates revealed a previously unappreciated ability of A. baumannii to vary surface molecules through horizontal gene transfer, with subsequent intraspecies dissemination by homologous recombination. These findings have immediate implications in surveillance, prevention, and treatment of A. baumannii infections.
C1 [Snitkin, Evan S.; Mijares, Lilia; Segre, Julie A.] NHGRI, Genet & Mol Biol Branch, Epithelial Biol Sect, Bethesda, MD 20892 USA.
[Zelazny, Adrian M.; Montero, Clemente I.; Stock, Frida; Mijares, Lilia; Murray, Patrick R.] Natl Inst Hlth Clin Ctr, Dept Lab Med, NIH, Bethesda, MD 20892 USA.
[NISC Comparative Sequence Program] Natl Inst Hlth Intramural Sequencing Ctr, NIH, Rockville, MD 20852 USA.
RP Murray, PR (reprint author), BD Diagnost, Sparks, MD 21152 USA.
EM Patrick_Murray@bd.com; jsegre@nhgri.nih.gov
FU National Institute of General Medical Sciences; National Human Genome
Research Institute; NIHCC
FX We thank members of the J.A.S. laboratory and National Institutes of
Health Intramural Sequencing Center (NISC) for critical reading of the
manuscript; Jyoti Gupta for confirming SNPs; and Effie Nomicos for chart
review. E.S.S. is supported by a Pharmacology Research Associate
Training Fellowship, National Institute of General Medical Sciences.
This work was supported by the National Human Genome Research Institute
and NIHCC Intramural Research Programs.
NR 39
TC 67
Z9 67
U1 2
U2 7
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD AUG 16
PY 2011
VL 108
IS 33
BP 13758
EP 13763
DI 10.1073/pnas.1104404108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 807KC
UT WOS:000293895100078
PM 21825119
ER
PT J
AU Poliakov, E
Parikh, T
Ayele, M
Kuo, S
Chander, P
Gentleman, S
Redmond, TM
AF Poliakov, Eugenia
Parikh, Toral
Ayele, Michael
Kuo, Stephanie
Chander, Preethi
Gentleman, Susan
Redmond, T. Michael
TI Aromatic Lipophilic Spin Traps Effectively Inhibit RPE65
Isomerohydrolase Activity
SO BIOCHEMISTRY
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; VISUAL CYCLE; CONGENITAL AMAUROSIS;
IN-VITRO; MUTATIONS; ISOMERIZATION; ISOMERASE; DEGENERATION; MECHANISM;
RADICALS
AB We previously showed that RPE65 does not specifically produce 11-cis-retinol only but also 13-cis-retinol, supporting a carbocation or radical cation mechanism of isomerization. The intrinsic properties of conjugated polyene chains result in facile formation of radical cations in oxidative conditions. We hypothesized that such radical intermediates, if involved in the mechanism of RPE65, could be stabilized by spin traps. We tested a variety of hydrophilic and lipophilic spin traps for their ability to inhibit RPE65 isomerohydrolase activity. We found that the aromatic lipophilic spin traps such as N-tert-butyl-alpha-phenylnitrone (PBN), 2,2-dimethyl-4-phenyl-2H-imidazole-1-oxide (DMPIO), and nitrosobenzene (NB) strongly inhibit RPE65 isomerohydrolase activity in vitro.
C1 [Poliakov, Eugenia; Parikh, Toral; Ayele, Michael; Kuo, Stephanie; Chander, Preethi; Gentleman, Susan; Redmond, T. Michael] NEI, LRCMB, NIH, Bethesda, MD 20892 USA.
RP Redmond, TM (reprint author), NEI, LRCMB, NIH, Bethesda, MD 20892 USA.
EM redmond@helix.nih.gov
OI Redmond, T. Michael/0000-0002-1813-5291
FU National Eye Institute, NIH; Howard Hughes Medical Institute (HHMI)
FX This research was supported by the Intramural Research Program of the
National Eye Institute, NIH. T.P. was supported by the Howard Hughes
Medical Institute (HHMI), while MA. was a HHMI/Montgomery County (MD)
Public Schools/NIH student intern when this work was performed.
NR 23
TC 12
Z9 12
U1 0
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD AUG 16
PY 2011
VL 50
IS 32
BP 6739
EP 6741
DI 10.1021/bi200532m
PG 3
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 804PI
UT WOS:000293665500001
PM 21736383
ER
PT J
AU Wang, HX
Gillis, A
Zhao, CY
Lee, E
Wu, J
Zhang, FC
Ye, F
Zhang, DY
AF Wang, Hongxia
Gillis, Andrew
Zhao, Chunyan
Lee, Eugene
Wu, Josephine
Zhang, Fengchun
Ye, Fei
Zhang, David Y.
TI Crocidolite asbestos-induced signal pathway dysregulation in mesothelial
cells
SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
LA English
DT Article
DE Immunoblot; Signaling network; Proteomics; Mesothelioma
ID MALIGNANT PLEURAL MESOTHELIOMA; MOLECULAR-BIOLOGY; NETWORK; UPDATE;
CANCER
AB Background: Malignant mesothelioma is a rare cancer caused by exposure to asbestos. Current therapies have limited efficacy and the prognosis is dismal. A better understanding of the underlying mechanism of asbestos-induced malignant transformation will help to identify molecular markers that can be used for diagnosis, prognosis or therapeutic targets.
Objectives: The objectives of this study are (1) to identify altered levels of proteins and phosphoproteins and (2) to establish the interactive network among those proteins in crocidolite-treated benign mesothelial cells and in malignant mesothelial cells.
Methods: Total cellular proteins were extracted from benign mesothelial cells, crocidolite-treated mesothelial cells and malignant mesothelial cells. The expression levels of 112 proteins and phosphoproteins were analyzed using a multiplex immunoblot-based assay followed by computational analysis (Protein Pathway Array).
Results: A total of 16 proteins/phosphoproteins (7 down-regulated and 9 up-regulated) were altered after exposure of benign mesothelial cells to crocidolite asbestos and the majority of them are involved in DNA damage repair and cell cycle regulation. In malignant mesothelial cells, 21 proteins/phosphoproteins (5 down-regulated and 16 up-regulated) were dysregulated and majority of them are involved in EGFR/ERK and PI3K/Akt pathways. Within the regulatory network affected by crocidolite, p53 and NF-kappa B complex are the most important regulators. There was substantial overlap in the regulatory networks between the asbestos-treated cells and malignant mesothelial cells.
Conclusions: Asbestos exposure has extensive effects on regulatory pathways and networks. These altered proteins may be used in the future to identify those with a high risk for developing malignant mesothelioma and as targets for preventing this deadly malignancy. (C) 2011 Elsevier B.V All rights reserved.
C1 [Ye, Fei] Mt Sinai Sch Med, Dept Pathol, New York, NY 10029 USA.
[Wang, Hongxia; Zhang, Fengchun] Shanghai Jiao Tong Univ, Sch Med, Shanghai Renji Hosp, Shanghai 200030, Peoples R China.
[Zhao, Chunyan] Jilin Univ, Dept Pathogenobiol, Changchun 130023, Peoples R China.
[Lee, Eugene] Natl Inst Biomed Imaging & Bioengn, Div Interdisciplinary Training, Bethesda, MD USA.
RP Ye, F (reprint author), Mt Sinai Sch Med, Dept Pathol, 1425 Madison Ave,Box 1122, New York, NY 10029 USA.
EM Feiyecc@gmail.com; David.zhang@mssm.edu
FU National Institute for Occupational Safety and Health (NIOSH) Mountain
and Plains Education and Research Center (MAP ERC); Shanghai Municipal
Education Committee [J50208]; Shanghai Municipal Natural Science
Foundation [09ZR1417900]
FX The study was partially supported by the National Institute for
Occupational Safety and Health (NIOSH) Mountain and Plains Education and
Research Center (MAP ERC) to F. Ye, the leading academic discipline
project of Shanghai Municipal Education Committee (Project Number:
J50208) to H. Wang and Shanghai Municipal Natural Science Foundation
(Project Number: 09ZR1417900) to H. Wang.
NR 24
TC 11
Z9 12
U1 2
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1383-5718
J9 MUTAT RES-GEN TOX EN
JI Mutat. Res. Genet. Toxicol. Environ. Mutagen.
PD AUG 16
PY 2011
VL 723
IS 2
BP 171
EP 176
DI 10.1016/j.mrgentox.2011.04.008
PG 6
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
GA 799VY
UT WOS:000293315400015
PM 21570478
ER
PT J
AU Yang, JH
Cisar, JO
Bush, CA
AF Yang, Jinghua
Cisar, John O.
Bush, C. Allen
TI Structure of type 3Gn coaggregation receptor polysaccharide from
Streptococcus cristatus LS4
SO CARBOHYDRATE RESEARCH
LA English
DT Article
DE Oral bacteria; Polysaccharides; Structure; NMR spectroscopy
ID CELL-SURFACE POLYSACCHARIDE; VIRIDANS GROUP STREPTOCOCCI; MOLECULAR
CHARACTERIZATION; CAPSULAR POLYSACCHARIDE; WALL POLYSACCHARIDES; ORALIS;
NMR; RECOGNITION; ACTINOMYCES; STRAINS
AB The presence of a novel coaggregation receptor polysaccharide (RPS) on the dental plaque isolate Streptococcus cristatus LS4 was suggested by this strain's antigenic and coaggregation properties. Examination of RPS isolated from strain LS4 by a combination of 2-dimensional and pseudo 3-dimensional single quantum heteronuclear NMR methods that included detection of (13)C chemical shifts at high resolution revealed the following repeat unit structure: -> 6)-beta-D-Galf-(1 -> 6)-beta-D-GalpNAc-(1 -> 3)-alpha-D-Galp-(1 -> P -> 6)-alpha-D-Galp-(1 -> 3)-beta-L-Rhap-(1 -> 4)-beta-D-Glcp-(1 ->. The identification of this polysaccharide as RPS3Gn, a new structural type, was established by the alpha-D-Galp-containing epitope of RPS serotype 3 and Gn recognition motif (i.e., beta-D-GalpNAc (1 -> 3)-alpha-D-Galp) for coaggregation with other bacteria. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Bush, C. Allen] Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD 21250 USA.
[Yang, Jinghua; Cisar, John O.] Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA.
RP Bush, CA (reprint author), Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD 21250 USA.
EM bush@umbc.edu
FU NIDCR, National Institutes of Health
FX We thank Mogens Kilian for help in identification of S. cristatus and
the Complex Carbohydrate Research Center at the University of Georgia
for chemical analyses. This work was supported by the Intramural
Research Program of the NIDCR, National Institutes of Health.
NR 24
TC 3
Z9 3
U1 0
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0008-6215
J9 CARBOHYD RES
JI Carbohydr. Res.
PD AUG 16
PY 2011
VL 346
IS 11
BP 1342
EP 1346
DI 10.1016/j.carres.2011.04.035
PG 5
WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 793YA
UT WOS:000292858600012
PM 21601178
ER
PT J
AU Chang, CM
Wang, SS
Dave, BJ
Jain, S
Vasef, MA
Weisenburger, DD
Cozen, W
Davis, S
Severson, RK
Lynch, CF
Rothman, N
Cerhan, JR
Hartge, P
Morton, LM
AF Chang, Cindy M.
Wang, Sophia S.
Dave, Bhavana J.
Jain, Smrati
Vasef, Mohammad A.
Weisenburger, Dennis D.
Cozen, Wendy
Davis, Scott
Severson, Richard K.
Lynch, Charles F.
Rothman, Nathaniel
Cerhan, James R.
Hartge, Patricia
Morton, Lindsay M.
TI Risk factors for non-Hodgkin lymphoma subtypes defined by histology and
t(14;18) in a population-based case-control study
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE lymphoma; non-Hodgkin; case-control studies; translocation; follicular
lymphoma; diffuse large B-cell lymphoma; etiology
ID EPIDEMIOLOGY CONSORTIUM INTERLYMPH; HAIR DYE USE; CIGARETTE-SMOKING;
PHYSICAL-ACTIVITY; POOLED ANALYSIS; UNITED-STATES; ANTHROPOMETRIC
CHARACTERISTICS; HEALTHY-INDIVIDUALS; ALCOHOL-CONSUMPTION;
PERIPHERAL-BLOOD
AB The t(14;18) chromosomal translocation is the most common cytogenetic abnormality in non-Hodgkin lymphoma (NHL), occurring in 70-90% of follicular lymphomas (FL) and 30-50% of diffuse large B-cell lymphomas (DLBCL). Previous t(14;18)-NHL studies have not evaluated risk factors for NHL defined by both t(14; 18) status and histology. In this population-based case-control study, t(14;18) status was determined in DLBCL cases using fluorescence in situ hybridization on paraffin-embedded tumor sections. Polytomous logistic regression was used to evaluate the association between a wide variety of exposures and t(14;18)-positive (N = 109) and -negative DLBCL (N = 125) and FL (N = 318), adjusting for sex, age, race, and study center. Taller height, more lifetime surgeries, and PCB180 exposure were associated with t(14;18)-positivity. Taller individuals (third tertile vs. first tertile) had elevated risks of t(14;18)-positive DLBCL (odds ratio [OR] = 1.8, 95% confidence interval [CI] 1.1-3.0) and FL (OR = 1.4, 95% CI 1.0-1.9) but not t(14;18)-negative DLBCL. Similar patterns were seen for individuals with more lifetime surgeries (131 vs. 0-12 surgeries; t(14;18)-positive DLBCL OR 5 1.4, 95% CI 0.7-2.7; FL OR = 1.6, 95% CI 1.1-2.5) and individuals exposed to PCB180 greater than 20.8 ng/g (t(14;18)-positive DLBCL OR = 1.3, 95% CI 0.6-2.9; FL OR = 1.7, 95% CI 1.0-2.8). In contrast, termite treatment and high alpha-chlordane levels were associated with t(14; 18)-negative DLBCL only, suggesting that these exposures do not act through t(14;18). Our findings suggest that putative associations between NHL and height, surgeries, and PCB180 may be t(14;18)-mediated and provide support for case-subtyping based on molecular and histologic subtypes. Future efforts should focus on pooling data to confirm and extend previous research on risk factors for t(14;18)-NHL subtypes.
C1 [Chang, Cindy M.; Wang, Sophia S.; Rothman, Nathaniel; Hartge, Patricia; Morton, Lindsay M.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD 20892 USA.
[Wang, Sophia S.] City Hope Natl Med Ctr, Dept Populat Sci, Div Canc Etiol, Duarte, CA USA.
[Wang, Sophia S.] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA.
[Dave, Bhavana J.; Jain, Smrati; Weisenburger, Dennis D.] Univ Nebraska Med Ctr, Omaha, NE USA.
[Vasef, Mohammad A.] Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA.
[Cozen, Wendy] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Davis, Scott] Univ Washington, Seattle, WA 98195 USA.
[Davis, Scott] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Severson, Richard K.] Wayne State Univ, Dept Family Med, Detroit, MI USA.
[Severson, Richard K.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
[Lynch, Charles F.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA.
[Cerhan, James R.] Mayo Clin, Coll Med, Div Epidemiol, Rochester, MN USA.
RP Chang, CM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Executive Blvd,EPS 7074, Rockville, MD 20892 USA.
EM changcm@mail.nih.gov
RI Chang, Cindy/G-4514-2010; Morton, Lindsay/B-5234-2015;
OI Morton, Lindsay/0000-0001-9767-2310; Cerhan, James/0000-0002-7482-178X
FU National Cancer Institute, National Institutes of Health, and Public
Health Service (PHS) [N01-PC-65064, N01-PC-67008, N01-PC-67009,
N01-PC-67010, N02-PC-71105]
FX Grant sponsor: Intramural Research Program of the National Cancer
Institute, National Institutes of Health, and Public Health Service
(PHS); Grant numbers: N01-PC-65064, N01-PC-67008, N01-PC-67009,
N01-PC-67010, and N02-PC-71105
NR 45
TC 10
Z9 10
U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD AUG 15
PY 2011
VL 129
IS 4
BP 938
EP 947
DI 10.1002/ijc.25717
PG 10
WC Oncology
SC Oncology
GA 789IC
UT WOS:000292508000019
PM 20949561
ER
PT J
AU Kranick, S
Ekanayake, V
Martinez, V
Ameli, R
Hallett, M
Voon, V
AF Kranick, Sarah
Ekanayake, Vindhya
Martinez, Valeria
Ameli, Rezvan
Hallett, Mark
Voon, Valerie
TI Psychopathology and Psychogenic Movement Disorders
SO MOVEMENT DISORDERS
LA English
DT Article
DE dystonia; movement disorders; psychogenic; psychological measures;
trauma
ID MOTOR CONVERSION DISORDER; CLINICAL CHARACTERISTICS; NONEPILEPTIC
SEIZURES; CHILDHOOD TRAUMA; ABUSE; DEPRESSION; DISABILITY; LIFE
AB Psychogenic movement disorder is defined as abnormal movements unrelated to a medical cause and presumed related to underlying psychological factors. Although psychological factors are of both clinical and pathophysiological relevance, very few studies to date have systematically assessed their role in psychogenic movement disorder. We sought to assess the role of previous life stress using validated quantitative measures in patients with psychogenic movement disorder compared with age- and sex-matched healthy volunteers as well as a convenience sample of patients with focal hand dystonia. Sixty-four patients with psychogenic movement disorder (72% female; mean age, 45.2 years [standard deviation, 15.2 years]), 38 healthy volunteers (74% female; mean age, 49 years [standard deviation, 13.7 years]), and 39 patients with focal hand dystonia (37% female; mean age, 48.7 years [standard deviation, 11.7 years]) were evaluated using a standardized psychological interview as well as validated quantitative scales to assess trauma and previous stressors, depression, anxiety, and personality traits. Patients with psychogenic movement disorder reported higher rates of childhood trauma, specifically greater emotional abuse and physical neglect, greater fear associated with traumatic events, and a greater number of traumatic episodes compared with healthy volunteers and patients with focal hand dystonia controlled for depressive symptoms and sex (Bonferroni corrected P < .005). There were no differences in categorical psychiatric diagnoses or scores on childhood physical or sexual abuse sub-scales, personality traits, or the dissociative experience scale. Our findings highlight a biopsychosocial approach toward the pathophysiology of psychogenic movement disorder, although the association with psychological issues is much less prominent than expected compared with the nonepileptic seizure population. A careful psychological assessment is indicated to optimize therapeutic modalities. (C)2011 Movement Disorder Society
C1 [Voon, Valerie] Univ Cambridge, Behav & Clin Neurosci Inst, Cambridge CB2 3EB, England.
[Kranick, Sarah; Martinez, Valeria; Hallett, Mark; Voon, Valerie] Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD USA.
[Ekanayake, Vindhya] Purdue Univ, Dept Psychol Sci, W Lafayette, IN 47907 USA.
[Ameli, Rezvan] NIMH, NIH, Bethesda, MD 20892 USA.
RP Voon, V (reprint author), Univ Cambridge, Behav & Clin Neurosci Inst, Downing Site, Cambridge CB2 3EB, England.
EM w247@cam.ac.uk
FU Intramural NIH HHS [Z01 NS002667-23]
NR 29
TC 51
Z9 51
U1 3
U2 18
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD AUG 15
PY 2011
VL 26
IS 10
BP 1844
EP 1850
DI 10.1002/mds.23830
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 822DS
UT WOS:000295024700009
PM 21714007
ER
PT J
AU Virtanen, JO
Pietilainen-Nicklen, J
Uotila, L
Farkkila, M
Vaheri, A
Koskiniemi, M
AF Virtanen, Jussi O.
Pietilainen-Nicklen, Jenna
Uotila, Lasse
Farkkila, Markus
Vaheri, Antti
Koskiniemi, Marjaleena
TI Intrathecal human herpesvirus 6 antibodies in multiple sclerosis and
other demyelinating diseases presenting as oligoclonal bands in
cerebrospinal fluid
SO JOURNAL OF NEUROIMMUNOLOGY
LA English
DT Article
DE Cerebrospinal fluid; Human herpesvirus 6; Intrathecal antibody; Multiple
sclerosis; Demyelination; Oligoclonal IgG bands
ID VIRUS-SPECIFIC IGG; DIAGNOSTIC-CRITERIA; IMMUNE-RESPONSE; IN-VITRO;
INFECTION; GENOME; CELLS; VIVO; MS
AB Demyelinating diseases of the central nervous system (CNS) often include elevated IgG production in intrathecal space presenting as oligoclonal bands (OCBs) in cerebrospinal fluid (CSF). In most demyelinating diseases, e.g. in multiple sclerosis (MS), the underlying cause is not known. We used isoelectric focusing and affinity immunoblot to study the specificity of CSF OCBs to human herpesvirus-6 (HHV-6) in patients with demyelinating diseases of the CNS including MS. Eighty patients with positive OCB finding were included in the study. The OCBs reacted with the HHV-6 antigen in 18 cases (23%). Twelve of 46 MS patients (26%), 5 of 24 other demyelinating diseases (21%) and 1 of 10 other neurological disorders (10%) had HHV-6 specific OCBs in CSF. A specific intrathecal HHV-6 A and B antibody production was shown in a proportion of patients with demyelinating diseases and might suggest a role in the pathogenesis of these diseases. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Virtanen, Jussi O.; Pietilainen-Nicklen, Jenna; Vaheri, Antti; Koskiniemi, Marjaleena] Univ Helsinki, Haartman Inst, Dept Virol, FIN-00014 Helsinki, Finland.
[Virtanen, Jussi O.; Vaheri, Antti] HUSLAB Lab Serv, Dept Virol, Helsinki, Finland.
[Pietilainen-Nicklen, Jenna; Farkkila, Markus] Univ Helsinki, Cent Hosp, Dept Neurol, Helsinki, Finland.
[Uotila, Lasse] HUSLAB Lab Serv, Dept Clin Chem, Helsinki, Finland.
RP Virtanen, JO (reprint author), NINDS, Neuroimmunol Branch, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM virtanenjo@ninds.nih.gov
RI Virtanen, Jussi Oskari/D-3253-2013
FU Biomedicum Helsinki Foundation; Finnish MS Foundation; Orion-Farmos
Foundation; Academy of Finland; Instrumentarium Foundation
FX The authors are grateful to Kari Borchers from ILS Laboratories
Scandinavia for providing Isofocusing gels and for technical help. Irina
Suomalainen and Sari Parkkamaki are thanked for technical help.
Biomedicum Helsinki Foundation, Finnish MS Foundation, Orion-Farmos
Foundation, Academy of Finland and Instrumentarium Foundation partially
funded the study.
NR 25
TC 15
Z9 15
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-5728
J9 J NEUROIMMUNOL
JI J. Neuroimmunol.
PD AUG 15
PY 2011
VL 237
IS 1-2
BP 93
EP 97
DI 10.1016/j.jneuroim.2011.06.012
PG 5
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 820VI
UT WOS:000294933800013
PM 21767883
ER
PT J
AU Laje, G
McMahon, FJ
AF Laje, Gonzalo
McMahon, Francis J.
TI Genome-wide association studies of antidepressant outcome: A brief
review
SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
LA English
DT Review
DE Antidepressant treatment outcome; Genome-wide association; GWAS;
Pharmacogenetics; Pharmacogenomics
ID GENE PROMOTER POLYMORPHISM; STAR-ASTERISK-D; MAJOR DEPRESSION;
PHARMACOGENETICS; METAANALYSIS; CITALOPRAM; IMPUTATION; EFFICACY
AB Genome-wide association studies (GWAS) of antidepressant treatment outcome have been at the forefront of psychiatric pharmacogenetics. Such studies may ultimately help match medications with patients, maximizing efficacy while minimizing adverse effects. The hypothesis-free approach of the GWAS has the advantage of interrogating genes that otherwise would have not been considered as candidates due to our limited understanding of their function, and may also uncover important regulatory variation within the large regions of the genome that do not contain protein-coding genes. Three independent samples have so far been studied using a genome-wide approach: The Sequenced Treatment Alternatives to Relieve Depression sample (STAR*D) (n = 1953), the Munich Antidepressant Response Signature (MARS) sample (n = 339) and the Genome-based Therapeutic Drugs for Depression (GENDEP) sample (n = 706). None of the studies reported results that achieved genome-wide significance, suggesting that larger samples and better outcome measures will be needed. This review discusses the published GWAS studies, their strengths, limitations, and possible future directions. Published by Elsevier Inc.
C1 [Laje, Gonzalo; McMahon, Francis J.] NIMH, Human Genet Branch, Intramural Res Program, NIH,US DHHS, Bethesda, MD 20892 USA.
RP Laje, G (reprint author), 35 Convent Dr,Rm 1A207, Bethesda, MD 20892 USA.
EM gonzalo.laje@nih.gov
RI Laje, Gonzalo/L-2654-2014;
OI Laje, Gonzalo/0000-0003-2763-3329; McMahon, Francis/0000-0002-9469-305X
FU NIMH; NIH, US DHHS [K99MH085098]
FX Drs. Laje and McMahon are listed as co-inventors in patent applications
filed by the NIH related to genetic markers of antidepressant treatment
outcome. Under federal law the NIH is required to pay inventors a
portion of any royalties the NIH receives through licenses granted under
patents. Funded by the Intramural Research Program of NIMH and
K99MH085098 (GL), NIH, US DHHS. 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 26
TC 21
Z9 21
U1 1
U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0278-5846
J9 PROG NEURO-PSYCHOPH
JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry
PD AUG 15
PY 2011
VL 35
IS 7
BP 1553
EP 1557
DI 10.1016/j.pnpbp.2010.11.031
PG 5
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 820YK
UT WOS:000294941800004
PM 21115088
ER
PT J
AU Greer, YE
Rubin, JS
AF Greer, Yoshimi Endo
Rubin, Jeffrey S.
TI The role of centrosomal casein kinase 1 delta in neurite outgrowth and
beyond
SO CELL CYCLE
LA English
DT Editorial Material
DE casein kinase 1 delta; centrosome; ciliogenesis; dishevelled; mitotic
spindle; neurite outgrowth; Wnt signaling
ID MITOTIC SPINDLE FORMATION; CELLS; INHIBITION; APOPTOSIS
C1 [Greer, Yoshimi Endo; Rubin, Jeffrey S.] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Rubin, JS (reprint author), NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM rubinj@mail.nih.gov
NR 10
TC 2
Z9 2
U1 1
U2 4
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD AUG 15
PY 2011
VL 10
IS 16
BP 2605
EP 2606
DI 10.4161/cc.10.16.16386
PG 2
WC Cell Biology
SC Cell Biology
GA 810VK
UT WOS:000294155600001
PM 21785261
ER
PT J
AU Ebersole, T
Kim, JH
Samoshkin, A
Kouprina, N
Pavlicek, A
White, RJ
Larionov, V
AF Ebersole, Thomas
Kim, Jung-Hyun
Samoshkin, Alexander
Kouprina, Natalay
Pavlicek, Adam
White, Robert J.
Larionov, Vladimir
TI tRNA genes protect a reporter gene from epigenetic silencing in mouse
cells
SO CELL CYCLE
LA English
DT Article
DE barrier elements; tRNA genes; Pol-III transcribed genes
ID POLYMERASE III TRANSCRIPTION; CHROMATIN-STRUCTURE; HETEROCHROMATIN
BARRIERS; SACCHAROMYCES-CEREVISIAE; CHROMOSOMAL INTEGRATION;
TRANSPOSABLE ELEMENTS; MOBILE ELEMENTS; BINDING-SITES; FISSION YEAST;
HUMAN GENOME
AB It is a well-established fact that the tRNA genes in yeast can function as chromatin barrier elements. However, so far there is no experimental evidence that tRNA and other Pol-III-transcribed genes exhibit barrier activity in mammals. This study utilizes a recently developed reporter gene assay to test a set of Pol-III-transcribed genes and gene clusters with variable promoter and intergenic regions for their ability to prevent heterochromatin-mediated reporter gene silencing in mouse cells. The results show that functional copies of mouse tRNA genes are effective barrier elements. The number of tRNA genes as well as their orientation influence barrier function. Furthermore, the DNA sequence composition of intervening and flanking regions affects barrier activity of tRNA genes. Barrier activity was maintained for much longer time when the intervening and flanking regions of tRNA genes were replaced by AT-rich sequences, suggesting a negative role of DNA methylation in the establishment of a functional barrier. Thus, our results suggest that tRNA genes are essential elements in establishment and maintenance of chromatin domain architecture in mammalian cells.
C1 [Ebersole, Thomas; Kim, Jung-Hyun; Samoshkin, Alexander; Kouprina, Natalay; Larionov, Vladimir] NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA.
[Pavlicek, Adam] Pfizer Global Res & Dev, Oncol Res Unit, Computat Biol, San Diego, CA USA.
[White, Robert J.] Beatson Inst Canc Res, Glasgow G61 1BD, Lanark, Scotland.
RP Larionov, V (reprint author), NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA.
EM larionov@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX Thanks to Mark Batzer for the Alu-Yb data, general support and
discussion. This research was supported by the intramural research
program of the NIH, National Cancer Institute, Center for Cancer
Research.
NR 55
TC 21
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U1 0
U2 3
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD AUG 15
PY 2011
VL 10
IS 16
BP 2779
EP 2791
DI 10.4161/cc.10.16.17092
PG 13
WC Cell Biology
SC Cell Biology
GA 810VK
UT WOS:000294155600033
PM 21822054
ER
PT J
AU Bercovitch, RS
Catanzaro, A
Schwartz, BS
Pappagianis, D
Watts, D
Ampel, NM
AF Bercovitch, Robert S.
Catanzaro, Antonino
Schwartz, Brian S.
Pappagianis, Demosthenes
Watts, D. Heather
Ampel, Neil M.
TI Coccidioidomycosis During Pregnancy: A Review and Recommendations for
Management
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Review
ID ANTLEY-BIXLER-SYNDROME; OF-THE-LITERATURE; CYTOCHROME-P450
OXIDOREDUCTASE; PULMONARY COCCIDIOIDOMYCOSIS; COMPLICATING PREGNANCY;
VAGINAL CANDIDIASIS; IMMITIS INFECTION; BREAST-MILK; FLUCONAZOLE;
MENINGITIS
AB The severity and risk for dissemination of coccidioidomycosis are increased when infection is acquired during pregnancy. Azole antifungals are potentially teratogenic when given in the first trimester. These issues are reviewed and guidance regarding management of coccidioidomycosis during pregnancy is provided.Pregnancy is an established risk factor for the development of severe and disseminated coccidioidomycosis, particularly when infection is acquired during the later stages of gestation. Although recent studies suggest that the incidence of symptomatic coccidioidomycosis during pregnancy is decreasing and that outcome has improved, management is complicated by the observations that azole antifungal agents can be teratogenic when given to some women, particularly at high doses, early in pregnancy. This article summarizes the data on these issues and offers guidance on the management of coccidioidomycosis during pregnancy.
C1 [Bercovitch, Robert S.; Catanzaro, Antonino] Univ Calif San Diego, San Diego, CA 92103 USA.
[Schwartz, Brian S.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Pappagianis, Demosthenes] Univ Calif Davis, Davis, CA 95616 USA.
[Watts, D. Heather] Eunice Kennedy Shriver Natl Inst Child Hlth & Hu, Bethesda, MD USA.
[Ampel, Neil M.] Univ Arizona, Valley Fever Ctr, Tucson, AZ USA.
[Ampel, Neil M.] So Arizona Vet Affairs Hlth Care Syst, Tucson, AZ USA.
RP Ampel, NM (reprint author), SAVAHCS, Med & Subspecialty Serv 1 111, 3601 S 6th Ave, Tucson, AZ 85745 USA.
EM nampel@email.arizona.edu
NR 72
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U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD AUG 15
PY 2011
VL 53
IS 4
BP 363
EP 368
DI 10.1093/cid/cir410
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 804DW
UT WOS:000293635500008
PM 21810749
ER
PT J
AU Taha, TE
Hoover, DR
Chen, S
Kumwenda, NI
Mipando, L
Nkanaunena, K
Thigpen, MC
Taylor, A
Fowler, MG
Mofenson, LM
AF Taha, Taha E.
Hoover, Donald R.
Chen, Shu
Kumwenda, Newton I.
Mipando, Linda
Nkanaunena, Kondwani
Thigpen, Michael C.
Taylor, Allan
Fowler, Mary Glenn
Mofenson, Lynne M.
TI Effects of Cessation of Breastfeeding in HIV-1-Exposed, Uninfected
Children in Malawi
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID HIV-INFECTED CHILDREN; INFANTS BORN; MORTALITY; TRANSMISSION;
COTRIMOXAZOLE; PROPHYLAXIS; BOTSWANA; MOTHERS; UGANDA; ZAMBIA
AB Background. We assessed morbidity rates during short intervals that accompanied weaning and cumulative mortality among HIV-exposed, uninfected infants enrolled in the postexposure prophylaxis of infants in Malawi (PEPI-Malawi) trial.
Methods. Women were counseled to stop breastfeeding (BF) by 6 months in the PEPI-Malawi trial. HIV-uninfected infants were included in this analysis starting at age 6 months. Breastfeeding and morbidity (illness and/or hospital admission and malnutrition [weight-for-age Z-score, < 2]) were assessed during age intervals of 6-9, 9-12, and 12-15 months. BF was defined as any BF at the start and end of the interval and no breastfeeding (NBF) was defined as NBF at any time during the interval. The association of NBF with morbidity at each mutually exclusive interval was assessed using Poisson regression models controlling for other factors. Cumulative mortality among infants aged 6-15 months with BF and NBF was assessed using an extended Kaplan-Meier method.
Results. At age 6 months, 1761 HIV-uninfected infants were included in the study. The adjusted rate ratios for illnesses and/or hospital admission for NBF, compared with BF, was 1.7 (P < .0001) at 6-9 months, 1.66 (P = .0001) at 9-12 months, and 1.75 (P = .0008) at 12-15 months. The rates of morbidity were consistently higher among NBF infants during each age interval, compared with BF infants. The 15 months cumulative mortality among BF and NBF children was 3.5% and 6.4% (P = .03), respectively.
Conclusions. Cessation of BF is associated with acute morbidity events and cumulative mortality. Prolonged BF should be encouraged, in addition to close monitoring of infant health and provision of support services.
C1 [Taha, Taha E.; Chen, Shu; Kumwenda, Newton I.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Hoover, Donald R.] Rutgers State Univ, Dept Stat, Piscataway, NJ USA.
[Hoover, Donald R.] Rutgers State Univ, Inst Hlth Hlth Policy & Aging Res, Piscataway, NJ USA.
[Mipando, Linda] Johns Hopkins Univ Res Project, Coll Med, Blantyre, Malawi.
[Nkanaunena, Kondwani; Fowler, Mary Glenn] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Thigpen, Michael C.; Taylor, Allan] Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Epidemiol Branch, Natl Ctr HIV AIDS Viral Hepatitis STD & TB Preven, Atlanta, GA USA.
[Mofenson, Lynne M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediatr Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH, Bethesda, MD USA.
RP Taha, TE (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Rm E7138,615 N Wolfe St, Baltimore, MD 21205 USA.
EM ttaha@jhsph.edu
OI Mofenson, Lynne/0000-0002-2818-9808
FU Centers for Disease Control and Prevention; Eunice Kennedy Shriver
National Institute of Child Health and Human Development, National
Institutes of Health [U50 PS022061-05, U50/CC0222061]
FX This work was supported by a Cooperative Agreement from the Centers for
Disease Control and Prevention and the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health (U50 PS022061-05; U50/CC0222061).
NR 28
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U1 1
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD AUG 15
PY 2011
VL 53
IS 4
BP 388
EP 395
DI 10.1093/cid/cir413
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 804DW
UT WOS:000293635500013
PM 21810754
ER
PT J
AU Sevy, S
Robinson, DG
Sunday, S
Napolitano, B
Miller, R
McCormack, J
Kane, J
AF Sevy, Serge
Robinson, Delbert G.
Sunday, Suzanne
Napolitano, Barbara
Miller, Rachel
McCormack, Joanne
Kane, John
TI Olanzapine vs. risperidone in patients with first-episode schizophrenia
and a lifetime history of cannabis use disorders: 16-week clinical and
substance use outcomes
SO PSYCHIATRY RESEARCH
LA English
DT Article
DE Psychosis; Marijuana; Atypicals; Alcohol; Negative symptoms; Positive
symptoms
ID PSYCHOSIS; CLOZAPINE; ONSET; MISUSE; TRIAL; ABUSE; HALOPERIDOL; ILLNESS;
ALCOHOL; SMOKING
AB The purpose of this study is to compare the efficacy of olanzapine and risperidone for the acute treatment of first-episode schizophrenia patients with cannabis use disorders. This secondary analysis of a previously published study included 49 first-episode patients with a diagnosis of schizophrenia, schizophreniform disorder, or schizoaffective disorder and a co-occurring lifetime diagnosis of cannabis use disorders randomly assigned to treatment with either olanzapine (n = 28) or risperidone (n = 21) for 16 weeks. The olanzapine group did not differ significantly from the risperidone group for initial response rates of positive symptoms, and rates of cannabis use or alcohol use during the study. Positive symptoms and the Scale for Assessment of Negative Symptoms (SANS) global asociality-anhedonia scores improved over time but did not differ between study medications. In both groups, cannabis use during the study was higher in patients who used cannabis within three months of the admission. Thus, our results suggest that olanzapine and risperidone had a similar initial efficacy on psychotic symptoms and substance use in first-episode patients with co-occurring cannabis use disorders. If clinicians are choosing between olanzapine versus risperidone treatment for this population, their decision should be based upon factors other than symptom response and short-term substance misuse. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
C1 [Sevy, Serge; Robinson, Delbert G.; Sunday, Suzanne; Napolitano, Barbara; Kane, John] Feinstein Inst Med Res, Manhasset, NY 11030 USA.
[Sevy, Serge; Robinson, Delbert G.; McCormack, Joanne; Kane, John] Zucker Hillside Hosp, Glen Oaks, NY 11004 USA.
[Sevy, Serge; Robinson, Delbert G.; Kane, John] Albert Einstein Coll Med, Bronx, NY 10461 USA.
[Sevy, Serge; Robinson, Delbert G.; Sunday, Suzanne; Kane, John] Hofstra N Shore LIJ Sch Med, Hempstead, NY 11549 USA.
[Miller, Rachel] NIMH, Bethesda, MD 20892 USA.
RP Sevy, S (reprint author), Feinstein Inst Med Res, 350 Community Dr, Manhasset, NY 11030 USA.
EM sevy@lij.edu
FU Bristol-Meyers Squibb; Eli Lilly; Janssen Pharmaceutica; NIH [K23
DA015541, MH60004, MH41960, RR018535]
FX Dr. Robinson has received grant support from Bristol-Meyers Squibb, Eli
Lilly, and Janssen Pharmaceutica. He has served as a speaker for Astra
Zeneca and Janssen Pharmaceutica. Dr. Kane has served as a consultant or
speaker for Astra Zeneca, Bristol-Myers Squibb. Cephalon, Eli Lilly,
GSK, Janssen Pharmaceutica, Johnson and Johnson, Lundbeck, Organon,
Otsuka, Pfizer Inc, PhXHealth, Proteus, Vanda, and Wyeth. He is a
shareholder of MedAvante. Dr. Sevy has served as a consultant for
Abbott. Dr. Sunday, Ms. Napolitano, Dr. Miller, and Ms. McCormack report
no competing interests. This work was supported by NIH grants K23
DA015541 (SS), MH60004 (DR), MH41960, and RR018535. The NIH had no
further role in study design; in the collection, analysis and
interpretation of data; in the writing of the report; and in the
decision to submit the paper for publication.
NR 24
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Z9 13
U1 0
U2 4
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0165-1781
J9 PSYCHIAT RES
JI Psychiatry Res.
PD AUG 15
PY 2011
VL 188
IS 3
BP 310
EP 314
DI 10.1016/j.psychres.2011.05.001
PG 5
WC Psychiatry
SC Psychiatry
GA 810QU
UT WOS:000294143000002
PM 21636134
ER
PT J
AU Buydens-Branchey, L
Branchey, M
Hibbeln, JR
AF Buydens-Branchey, Laure
Branchey, Marc
Hibbeln, Joseph R.
TI Higher n-3 fatty acids are associated with more intense
fenfluramine-induced ACTH and cortisol responses among cocaine-abusing
men
SO PSYCHIATRY RESEARCH
LA English
DT Article
DE Serotonin probe; Hormonal responses; EPA; DHA
ID DOCOSAHEXAENOIC ACID; SEROTONINERGIC NEUROTRANSMISSION;
CEREBROSPINAL-FLUID; NERVOUS-SYSTEM; OMEGA-3-FATTY-ACIDS; BRAIN;
DEPRESSION; TRYPTOPHAN; DISORDERS; ALPHA
AB Preclinical studies have shown that diets supplemented with or deficient in n-3 polyunsaturated fatty acids (PUFAs) could influence serotonergic neurotransmission, but information about their effects on the serotonergic function of humans is scant. Therefore, simultaneous assessments of n-3 PUFAs and of the adrenocorticotropic hormone (ACTH) and cortisol responses to challenges with the serotonin (5-HT) probe d,l-fenfluramine (FEN) were performed in 25 cocaine-abusing men and 12 control subjects. Cocaine abusers were tested 18 days after their admission to a closed ward. ACTH and cortisol were measured in plasma samples collected on two testing days separated by 48 h following the random administration of 60 mg of FEN or placebo. Fatty acids were measured in the first test day samples. Patients' FEN-induced ACTH rises were significantly and positively correlated with docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Patients' cortisol rises were positively and significantly correlated with EPA but not with DHA. There were no significant correlations between hormonal responses and pre-hospitalization cocaine use parameters. Control subjects' responses to FEN were not correlated with any PUFA. In conclusion, higher EPA and DHA levels were associated with a more intense FEN-induced ACTH response and higher EPA levels with a more intense cortisol response in cocaine-abusing men withdrawn from cocaine but not in control subjects. These findings support and expand existing evidence that EPA and DHA could influence 5-HT function in some human subgroups. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
C1 [Buydens-Branchey, Laure] Narrows Inst Biomed Res, NYHHS, Brooklyn, NY 11209 USA.
[Hibbeln, Joseph R.] NIAAA, Bethesda, MD USA.
RP Buydens-Branchey, L (reprint author), Narrows Inst Biomed Res, NYHHS, Brooklyn Campus,800 Poly Pl, Brooklyn, NY 11209 USA.
EM lbuydens@att.net
FU National Institute on Drug Abuse [R01-DA15360]; National Institute on
Alcohol Abuse and Alcoholism
FX This work was supported by grant R01-DA15360 from the National Institute
on Drug Abuse and by the National Institute on Alcohol Abuse and
Alcoholism.
NR 37
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Z9 3
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0165-1781
J9 PSYCHIAT RES
JI Psychiatry Res.
PD AUG 15
PY 2011
VL 188
IS 3
BP 422
EP 427
DI 10.1016/j.psychres.2011.05.027
PG 6
WC Psychiatry
SC Psychiatry
GA 810QU
UT WOS:000294143000020
PM 21658782
ER
PT J
AU Atochina-Vasserman, EN
Bates, SR
Zhang, P
Abramova, H
Zhang, ZG
Gonzales, L
Tao, JQ
Gochuico, BR
Gahl, W
Guo, CJ
Gow, AJ
Beers, MF
Guttentag, S
AF Atochina-Vasserman, Elena N.
Bates, Sandra R.
Zhang, Peggy
Abramova, Helen
Zhang, Zhenguo
Gonzales, Linda
Tao, Jian-Qin
Gochuico, Bernadette R.
Gahl, William
Guo, Chang-Jiang
Gow, Andrew J.
Beers, Michael F.
Guttentag, Susan
TI Early Alveolar Epithelial Dysfunction Promotes Lung Inflammation in a
Mouse Model of Hermansky-Pudlak Syndrome
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE Hermansky-Pudlak syndrome; S-nitrosylation; surfactant protein D; lung
remodeling
ID SURFACTANT-PROTEIN-D; IDIOPATHIC PULMONARY-FIBROSIS; INTERSTITIAL
PNEUMONIA; COMPONENT EXPRESSION; S-NITROSYLATION; CELLS; INJURY; TYPE-2;
MICE; COLLECTINS
AB Rationale: The pulmonary phenotype of Hermansky-Pudlak syndrome (HPS) in adults includes foamy alveolar type 2 cells, inflammation, and lung remodeling, but there is no information about ontogeny or early disease mediators.
Objectives: To establish the ontogeny of HPS lung disease in an animal model, examine disease mediators, and relate them to patients with HPS1.
Methods: Mice with mutations in both HPS1/pale ear and HPS2/AP3B1/pearl (EPPE mice) were studied longitudinally. Total lung homogenate, lung tissue sections, and bronchoalveolar lavage (BAL) were examined for phospholipid, collagen, histology, cell counts, chemokines, surfactant protein D (SP-D), and S-nitrosylated SP-D. Isolated alveolar epithelial cells were examined for expression of inflammatory mediators, and chemotaxis assays were used to assess their importance. Pulmonary function test results and BAL from patients with HPS1 and normal volunteers were examined for clinical correlation.
Measurements and Main Results: EPPE mice develop increased total lung phospholipid, followed by a macrophage-predominant pulmonary inflammation, and lung remodeling including fibrosis. BAL fluid from EPPE animals exhibited early accumulation of both SP-D and S-nitrosylated SP-D. BAL fluid from patients with HPS1 exhibited similar changes in SP-D that correlated inversely with pulmonary function. Alveolar epithelial cells demonstrated expression of both monocyte chemotactic protein (MCP)-1 and inducible nitric oxide synthase in juvenile EPPE mice. Last, BAL from EPPE mice and patients with HPS1 enhanced migration of RAW267.4 cells, which was attenuated by immunodepletion of SP-D and MCP-1.
Conclusions: Inflammation is initiated from the abnormal alveolar epithelial cells in HPS, and S-nitrosylated SP-D plays a significant role in amplifying pulmonary inflammation.
C1 [Atochina-Vasserman, Elena N.; Abramova, Helen; Beers, Michael F.] Univ Penn, Sch Med, Div Pulm & Crit Care Med, Philadelphia, PA 19104 USA.
[Bates, Sandra R.; Tao, Jian-Qin] Univ Penn, Sch Med, Inst Environm Med, Philadelphia, PA 19104 USA.
[Zhang, Peggy; Zhang, Zhenguo; Gonzales, Linda; Guttentag, Susan] Childrens Hosp Philadelphia, Dept Pediat, Div Neonatol, Philadelphia, PA 19104 USA.
[Gochuico, Bernadette R.; Gahl, William] NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Abramova, Helen; Guo, Chang-Jiang; Gow, Andrew J.] Rutgers State Univ, Ernest Mario Sch Pharm, Dept Pharmacol, Piscataway, NJ USA.
RP Guttentag, S (reprint author), 416G Abramson Res Ctr, 3615 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM guttentag@email.chop.edu
RI Guttentag, Susan/D-8705-2013; Gow, Andrew/N-8566-2013
OI Guttentag, Susan/0000-0003-4420-5879; Gow, Andrew/0000-0003-0876-5158
FU National Human Genome Research Institute, National Institutes of Health;
National Institutes of Health [HL086621, HL019737, HL064520, ES013508,
HL059959]; Mead Johnson; Abbott Nutritionals; American Heart Association
FX Supported by the Intramural Research Program of the National Human
Genome Research Institute, National Institutes of Health (B.R.G., W.G.),
and by extramural funding from the National Institutes of Health through
HL086621 (A.J.G.), HL019737 (S.R.B., M.F.B.), HL064520 (M.F.B.),
ES013508 (M.F.B.), and HL059959 (S.G.).; E.N.A.-V., S.R.B., P.Z., H.A.,
Z.Z., L.G., J.-Q.T., B.R.G., W.G., C.-J.G., A.J.G., and M.F.B. do not
have a financial relationship with a commercial entity that has an
interest in the subject of this manuscript. S. G. received lecture fees
from Mead Johnson and Abbott Nutritionals, and received grant support
from the American Heart Association.
NR 46
TC 18
Z9 18
U1 0
U2 5
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD AUG 15
PY 2011
VL 184
IS 4
BP 449
EP 458
DI 10.1164/rccm.201011-1882OC
PG 10
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 808EL
UT WOS:000293959600015
PM 21616998
ER
PT J
AU Willett, M
Brocard, M
Davide, A
Morley, SJ
AF Willett, Mark
Brocard, Michele
Davide, Alexandre
Morley, Simon J.
TI Translation initiation factors and active sites of protein synthesis
co-localize at the leading edge of migrating fibroblasts
SO BIOCHEMICAL JOURNAL
LA English
DT Article
DE Golgi apparatus; localization; membrane microdomain; translation
initiation factor
ID MESSENGER-RNA LOCALIZATION; ENDOPLASMIC-RETICULUM; MAMMALIAN-CELLS;
POLY(A)-BINDING PROTEIN-1; HYPERTONIC STRESS; COMPLEX; GOLGI; MTOR;
TRANSPORT; MECHANISMS
AB Cell migration is a highly controlled essential cellular process, often dysregulated in tumour cells, dynamically controlled by the architecture of the cell. Studies involving cellular fractionation and microarray profiling have previously identified functionally distinct mRNA populations specific to cellular organelles and architectural compartments. However, the interaction between the translational machinery itself and cellular structures is relatively unexplored. To help understand the role for the compartmentalization and localized protein synthesis in cell migration, we have used scanning confocal microscopy, immunofluorescence and a novel ribopuromycylation method to visualize translating ribosomes. In the present study we show that eIFs (eukaryotic initiation factors) localize to the leading edge of migrating MRCS fibroblasts in a process dependent on TGN (trans-Golgi network) to plasma membrane vesicle transport. We show that eIF4E and eIF4GI are associated with the Golgi apparatus and membrane microdomains, and that a proportion of these proteins co-localize to sites of active translation at the leading edge of migrating cells.
C1 [Willett, Mark; Brocard, Michele; Morley, Simon J.] Univ Sussex, Dept Biochem, Sch Life Sci, Brighton BN1 9QG, E Sussex, England.
NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Morley, SJ (reprint author), Univ Sussex, Dept Biochem, Sch Life Sci, Brighton BN1 9QG, E Sussex, England.
EM s.j.morley@sussex.ac.uk
OI David, Alexandre/0000-0003-3365-1339
FU Biotechnology and Biological Sciences Research Council (UK)
[BB/H018956/1]
FX This work was supported by the Biotechnology and Biological Sciences
Research Council (UK) [grant number BB/H018956/1].
NR 67
TC 16
Z9 16
U1 0
U2 9
PU PORTLAND PRESS LTD
PI LONDON
PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND
SN 0264-6021
J9 BIOCHEM J
JI Biochem. J.
PD AUG 15
PY 2011
VL 438
BP 217
EP 227
DI 10.1042/BJ20110435
PN 1
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 809UY
UT WOS:000294083400021
PM 21539520
ER
PT J
AU May, KF
Gulley, JL
Drake, CG
Dranoff, G
Kantoff, PW
AF May, Kenneth F., Jr.
Gulley, James L.
Drake, Charles G.
Dranoff, Glenn
Kantoff, Philip W.
TI Prostate Cancer Immunotherapy
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID CD8(+) T-CELLS; CTLA-4 BLOCKADE; COMBINATION IMMUNOTHERAPY;
ANDROGEN-DEPRIVATION; ANTITUMOR IMMUNITY; TUMOR; PD-1; EFFECTOR;
THERAPY; MICE
AB The interaction between the immune system and prostate cancer has been an area of research interest for several decades. The recent U. S. Food and Drug Administration approval of 2 first-in-class proof-of-concept immunotherapies (sipuleucel-T and ipilimumab) has stimulated broader interest in manipulating immunity to fight cancer. In the context of prostate cancer, the immunotherapy strategies that have garnered the most interest are the therapeutic vaccination strategies, exemplified by sipuleucel-T and PROSTVAC-VF, and immune checkpoint blockade of CTLA-4 and PD-1. Improved understanding of the immune responses generated by these strategies and development of predictive biomarkers for patient selection will guide rational combinations of these treatments and provide building blocks for future immunotherapies. Clin Cancer Res; 17(16); 5233-8. (C)2011 AACR.
C1 [May, Kenneth F., Jr.; Dranoff, Glenn; Kantoff, Philip W.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[May, Kenneth F., Jr.; Dranoff, Glenn] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02215 USA.
[May, Kenneth F., Jr.; Dranoff, Glenn; Kantoff, Philip W.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[May, Kenneth F., Jr.; Dranoff, Glenn; Kantoff, Philip W.] Harvard Univ, Sch Med, Boston, MA USA.
[Gulley, James L.] NCI, Clin Trials Grp, Tumor Immunol & Biol Lab, Med Oncol Branch,Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Drake, Charles G.] Johns Hopkins Sch Med, James Buchanan Brady Urol Inst, Dept Urol,Dept Oncol, Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
RP May, KF (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Smith 353, Boston, MA 02215 USA.
EM kmay1@partners.org
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
FU Prostate Cancer Foundation; NIH, National Cancer Institute; Center for
Cancer Research; NIH [R01 CA127153, 1P50CA58236-15, CA143083, CA78378,
5P01CA089021-10, 5P50CA090381-09]; Patrick C. Walsh Fund; OneInSix
Foundation; Leukemia & Lymphoma Society; Melanoma Research Alliance;
Alliance for Cancer Gene Therapy; Research Foundation for the Treatment
of Ovarian Cancer; Department of Defense
FX Prostate Cancer Foundation Young Investigator Award (K. F. May);
Intramural Research Program of the NIH, National Cancer Institute, and
Center for Cancer Research (J.L. Gulley); NIH R01 CA127153 and
1P50CA58236-15, the Patrick C. Walsh Fund, the OneInSix Foundation, and
the Prostate Cancer Foundation (C. G. Drake); NIH CA143083 and CA78378,
Leukemia & Lymphoma Society, Melanoma Research Alliance, Alliance for
Cancer Gene Therapy, and Research Foundation for the Treatment of
Ovarian Cancer (G. Dranoff); NIH 5P01CA089021-10 and 5P50CA090381-09,
Prostate Cancer Foundation, and Department of Defense (P. W. Kantoff).
NR 52
TC 35
Z9 35
U1 2
U2 11
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD AUG 15
PY 2011
VL 17
IS 16
BP 5233
EP 5238
DI 10.1158/1078-0432.CCR-10-3402
PG 6
WC Oncology
SC Oncology
GA 806VN
UT WOS:000293843700004
PM 21700764
ER
PT J
AU Klebanoff, CA
Gattinoni, L
Palmer, DC
Muranski, P
Ji, Y
Hinrichs, CS
Borman, ZA
Kerkar, SP
Scott, CD
Finkelstein, SE
Rosenberg, SA
Restifo, NP
AF Klebanoff, Christopher A.
Gattinoni, Luca
Palmer, Douglas C.
Muranski, Pawel
Ji, Yun
Hinrichs, Christian S.
Borman, Zachary A.
Kerkar, Sid P.
Scott, Christopher D.
Finkelstein, Steven E.
Rosenberg, Steven A.
Restifo, Nicholas P.
TI Determinants of Successful CD8(+) T-Cell Adoptive Immunotherapy for
Large Established Tumors in Mice
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID METASTATIC MELANOMA PATIENTS; IN-VIVO; PHASE-I; INFILTRATING
LYMPHOCYTES; CANCER REGRESSION; ANTITUMOR-ACTIVITY; TRANSFER THERAPY;
GENE-THERAPY; STEM-CELLS; MEMORY
AB Purpose: Adoptive cell transfer (ACT) of tumor infiltrating or genetically engineered T cells can cause durable responses in patients with metastatic cancer. Multiple clinically modifiable parameters can comprise this therapy, including cell dose and phenotype, in vivo antigen restimulation, and common gamma-chain (gamma(c)) cytokine support. However, the relative contributions of each these individual components to the magnitude of the antitumor response have yet to be quantified.
Experimental Design: To systematically and quantitatively appraise each of these variables, we employed the Pmel-1 mouse model treating large, established B16 melanoma tumors. In addition to cell dose and magnitude of in vivo antigen restimulation, we also evaluated the relative efficacy of central memory (T(CM)), effector memory (T(EM)), and stem cell memory (T(SCM)) subsets on the strength of tumor regression as well as the dose and type of clinically available gamma(c) cytokines, including IL-2, IL-7, IL-15, and IL-21.
Results: We found that cell dose, T-cell differentiation status, and viral vaccine titer each were correlated strongly and significantly with the magnitude of tumor regression. Surprisingly, although the total number of IL-2 doses was correlated with tumor regression, no significant benefit to prolonged (>= 6 doses) administration was observed. Moreover, the specific type and dose of gamma(c) cytokine only moderately correlated with response.
Conclusion: Collectively, these findings elucidate some of the key determinants of successful ACT immunotherapy for the treatment of cancer in mice and further show that gamma(c) cytokines offer a similar ability to effectively drive antitumor T-cell function in vivo. Clin Cancer Res; 17(16); 5343-52. (C)2011 AACR.
C1 [Klebanoff, Christopher A.; Gattinoni, Luca; Palmer, Douglas C.; Muranski, Pawel; Ji, Yun; Hinrichs, Christian S.; Borman, Zachary A.; Kerkar, Sid P.; Scott, Christopher D.; Finkelstein, Steven E.; Rosenberg, Steven A.; Restifo, Nicholas P.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Klebanoff, CA (reprint author), NCI, Ctr Canc Res, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM klebanoc@mail.nih.gov; NPR@nih.gov
RI Gattinoni, Luca/A-2281-2008; Ji, Yun/B-7245-2009; Restifo,
Nicholas/A-5713-2008; Palmer, Douglas/B-9454-2008;
OI Gattinoni, Luca/0000-0003-2239-3282; Ji, Yun/0000-0001-6340-7009;
Palmer, Douglas/0000-0001-5018-5734; Restifo, Nicholas
P./0000-0003-4229-4580
FU NCI, Center for Cancer Research, NIH, Bethesda, MD
FX This study was funded in part by the intramural research program of the
NCI, Center for Cancer Research, NIH, Bethesda, MD. This article was
written in partial fulfillment of a PhD degree for the George Washington
University, Washington, DC (D.C. Palmer).
NR 65
TC 100
Z9 103
U1 2
U2 27
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD AUG 15
PY 2011
VL 17
IS 16
BP 5343
EP 5352
DI 10.1158/1078-0432.CCR-11-0503
PG 10
WC Oncology
SC Oncology
GA 806VN
UT WOS:000293843700015
PM 21737507
ER
PT J
AU Lim, WT
Ng, QS
Ivy, P
Leong, SS
Singh, O
Chowbay, B
Gao, F
Thng, CH
Goh, BC
Tan, DSW
Koh, TS
Toh, CK
Tan, EH
AF Lim, Wan-Teck
Ng, Quan-Sing
Ivy, Percy
Leong, Swan-Swan
Singh, Onkar
Chowbay, Balram
Gao, Fei
Thng, Choon Hua
Goh, Boon-Cher
Tan, Daniel Shao-Weng
Koh, Tong San
Toh, Chee-Keong
Tan, Eng-Huat
TI A Phase II Study of Pazopanib in Asian Patients with
Recurrent/Metastatic Nasopharyngeal Carcinoma
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; TUMOR ANGIOGENESIS; PROGNOSTIC-FACTORS; CELL
CARCINOMA; FDG-PET; RECURRENT; THERAPY; TRIAL; CT; EXPRESSION
AB Purpose: Nasopharyngeal carcinoma is endemic in Asia and angiogenesis is important for growth and progression. We hypothesized that pazopanib would have antiangiogenic activity in nasopharyngeal carcinoma.
Experimental Design: A single arm monotherapy study of pazopanib in patients with WHO type II/III nasopharyngeal carcinoma who had metastatic/recurrent disease and failed at least one line of chemotherapy. A Simon's optimal 2-stage design was used. Patients with Eastern Cooperative Oncology Group (ECOG) 0-2 and adequate organ function were treated with pazopanib 800 mg daily on a 21-day cycle. The primary endpoint was clinical benefit rate (CR/PR/SD) achieved after 12 weeks of treatment. Secondary endpoints included toxicity and progression-free survival. Exploratory studies of dynamic-contrast enhanced computed tomography (DCE-CT) paired with pharmacokinetics (PK) of pazopanib was done.
Results: Thirty-three patients were accrued. Patients were ECOG 0-1 with median age of 50 years (range 36-68). There were 2 (6.1%) partial responses, 16 (48.5%) stable disease, 11 (33.3%) progressive disease, 4 (12.1%) were not evaluable for response. The clinical benefit rate was 54.5% (95% CI: 38.0-70.2). Ten patients (30.3%) received more than 6 cycles (4 months) of treatment and 7 (21.2%) had PR/SD that lasted at least 6 months. One patient each died from epistaxis and myocardial infarction. Common grade 3/4 toxicities included fatigue (15.2%), hand-foot syndrome (15.2%), anorexia (9.1%), diarrhea (6.1%), and vomiting (6.1%). Serial DCE-CT scans show significant reductions in tumor blood flow, permeability surface area product, and fractional intravascular blood volume.
Conclusion: Pazopanib showed encouraging activity in heavily pretreated nasopharyngeal carcinoma with an acceptable toxicity profile. Clin Cancer Res; 17(16); 5481-9. (C)2011 AACR.
C1 [Lim, Wan-Teck; Ng, Quan-Sing; Leong, Swan-Swan; Tan, Daniel Shao-Weng; Toh, Chee-Keong; Tan, Eng-Huat] Natl Canc Ctr Singapore, Dept Med Oncol, Singapore 169610, Singapore.
[Thng, Choon Hua; Koh, Tong San] Natl Canc Ctr Singapore, Dept Oncol Imaging, Singapore 169610, Singapore.
[Gao, Fei] Natl Canc Ctr Singapore, Div Clin Trials & Epidemiol Sci, Singapore 169610, Singapore.
[Ivy, Percy] NCI, Canc Therapy Evaluat Program, Rockville, MD USA.
RP Lim, WT (reprint author), Natl Canc Ctr Singapore, Dept Med Oncol, 11 Hosp Dr, Singapore 169610, Singapore.
EM dmolwt@nccs.com.sg
RI KOH, TONG SAN/A-5027-2011
FU Singapore Cancer Syndicate [SCS-CS-0072]; Biomedical Research Council,
Singapore [BMRC/08/1/31/19/577]; NCI CTEP
FX This work was funded in part by the Singapore Cancer Syndicate
(SCS-CS-0072) and Biomedical Research Council, Singapore
(BMRC/08/1/31/19/577) research grants and supported by NCI CTEP.
NR 41
TC 30
Z9 30
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD AUG 15
PY 2011
VL 17
IS 16
BP 5481
EP 5489
DI 10.1158/1078-0432.CCR-10-3409
PG 9
WC Oncology
SC Oncology
GA 806VN
UT WOS:000293843700028
PM 21712450
ER
PT J
AU Stone, JE
Kumar, D
Binz, SK
Inase, A
Iwai, S
Chabes, A
Burgers, PM
Kunkel, TA
AF Stone, Jana E.
Kumar, Dinesh
Binz, Sara K.
Inase, Aki
Iwai, Shigenori
Chabes, Andrei
Burgers, Peter M.
Kunkel, Thomas A.
TI Lesion bypass by S-cerevisiae Pol zeta alone
SO DNA REPAIR
LA English
DT Article
DE DNA polymerase zeta; Translesion synthesis; UV photoproducts; Abasic
sites
ID DNA-POLYMERASE-ZETA; DEPENDENT TRANSLESION SYNTHESIS; THYMINE-THYMINE
DIMER; STRAND-BREAK-REPAIR; EMBRYONIC LETHALITY; REV1 PROTEIN;
ERROR-FREE; INDUCED MUTAGENESIS; CATALYTIC SUBUNIT; ABASIC SITES
AB DNA polymerase zeta (Pol zeta) participates in translesion synthesis (TLS) of DNA adducts that stall replication fork progression. Previous studies have led to the suggestion that the primary role of Pol zeta in TLS is to extend primers created when another DNA polymerase inserts nucleotides opposite lesions. Here we test the non-exclusive possibility that Pol zeta can sometimes perform TLS in the absence of any other polymerase. To do so, we quantified the efficiency with which S. cerevisiae Pol zeta bypasses abasic sites, cis-syn cyclobutane pyrimidine dimers and (6-4) photoproducts. In reactions containing dNTP concentrations that mimic those induced by DNA damage, a Pol zeta derivative with phenylalanine substituted for leucine 979 at the polymerase active site bypasses all three lesions at efficiencies between 27 and 73%. Wild-type Pol zeta also bypasses these lesions, with efficiencies that are lower and depend on the sequence context in which the lesion resides. The results are consistent with the hypothesis that, in addition to extending aberrant termini created by other DNA polymerases, Pol zeta has the potential to be the sole DNA polymerase involved in TLS. Published by Elsevier B.V.
C1 [Stone, Jana E.; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Stone, Jana E.; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Kumar, Dinesh; Chabes, Andrei] Umea Univ, Dept Med Biochem & Biophys, SE-90187 Umea, Sweden.
[Kumar, Dinesh; Chabes, Andrei] Umea Univ, Lab Mol Infect Med Sweden MIMS, SE-90187 Umea, Sweden.
[Binz, Sara K.; Burgers, Peter M.] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA.
[Inase, Aki; Iwai, Shigenori] Osaka Univ, Grad Sch Engn Sci, Div Chem, Osaka 5608531, Japan.
RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
EM kunkel@niehs.nih.gov
FU Division of Intramural Research of the National Institute of
Environmental Health Sciences, National Institutes of Health [Z01
ES065070]; Swedish Foundation for Strategic Research; Swedish Research
Council; Swedish Cancer Society; National Institutes of Health
[GM032431]; Ministry of Education, Culture, Sports, Science, and
Technology, Japan
FX We thank Mercedes Arana, Katarzyna Bebenek and Danielle Watt for helpful
comments on the manuscript. This work was supported in part by the
Division of Intramural Research of the National Institute of
Environmental Health Sciences, National Institutes of Health [Project
Z01 ES065070 to TAK], by the Swedish Foundation for Strategic Research,
the Swedish Research Council and the Swedish Cancer Society [to AC], by
National Institutes of Health [grant GM032431 to PMB] and by
Grant-in-Aid for Scientific Research from the Ministry of Education,
Culture, Sports, Science, and Technology, Japan [to SI].
NR 60
TC 19
Z9 19
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
J9 DNA REPAIR
JI DNA Repair
PD AUG 15
PY 2011
VL 10
IS 8
BP 826
EP 834
DI 10.1016/j.dnarep.2011.04.032
PG 9
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA 809EE
UT WOS:000294033800005
PM 21622032
ER
PT J
AU Watt, DL
Johansson, E
Burgers, PM
Kunkel, TA
AF Watt, Danielle L.
Johansson, Erik
Burgers, Peter M.
Kunkel, Thomas A.
TI Replication of ribonucleotide-containing DNA templates by yeast
replicative polymerases
SO DNA REPAIR
LA English
DT Article
DE DNA replication; Ribonucleotides; rNMP bypass; Translesion synthesis
ID REVERSE-TRANSCRIPTASE; FIDELITY; RESIDUE; FAMILY; DISCRIMINATION;
EFFICIENCY; INSERTION; MUTANTS; EPSILON; BYPASS
AB The major replicative DNA polymerases of S. cerevisiae (Pots alpha, delta, and epsilon) incorporate substantial numbers of ribonucleotides into DNA during DNA synthesis. When these ribonucleotides are not removed in vivo, they reside in the template strand used for the next round of replication and could potentially reduce replication efficiency and fidelity. To examine if the presence of ribonucleotides in a DNA template impede DNA synthesis, we determined the efficiency with which Pols alpha, delta, and epsilon copy DNA templates containing a single ribonucleotide. All three polymerases can replicate past ribonucleotides. Relative to all-DNA templates, bypass of ribo-containing templates is slightly reduced, to extents that depend on the identity of the ribo and the sequence context in which it resides. Bypass efficiencies for Pols delta and epsilon were increased by increasing the dNTP concentrations to those induced by cellular stress, and in the case of Pol epsilon, by inactivating the 3'-exonuclease activity. Overall, ribonucleotide bypass efficiencies are comparable to, and usually exceed, those for the common oxidative stress-induced lesion 8-oxo-guanine. Published by Elsevier B.V.
C1 [Watt, Danielle L.; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Watt, Danielle L.; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Johansson, Erik] Umea Univ, Dept Med Biochem & Biophys, SE-90187 Umea, Sweden.
[Burgers, Peter M.] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA.
RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
EM kunkel@niehs.nih.gov
FU Division of Intramural Research of the NIH, NIEHS [Z01 ES065070];
Swedish Research Council; Swedish Cancer Society, Smartafonden; Medical
Faculty of Umea University; NIH [GM032431]
FX We thank Katarzyna Bebenek and Jessica Williams for helpful comments on
the manuscript, Amy Abdulovic for providing purified Pol delta
holoenzyme, and Else-Britt Lundstrom for providing purified Pol epsilon
enzymes. This work was supported by Project Z01 ES065070 to T.A.K. from
the Division of Intramural Research of the NIH, NIEHS, by the Swedish
Research Council, the Swedish Cancer Society, Smartafonden and the fund
for Basic Science-oriented Biotechnology, Medical Faculty of Umea
University to E.J., and by NIH grant GM032431 to P.M.B.
NR 41
TC 29
Z9 29
U1 0
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
J9 DNA REPAIR
JI DNA Repair
PD AUG 15
PY 2011
VL 10
IS 8
BP 897
EP 902
DI 10.1016/j.dnarep.2011.05.009
PG 6
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA 809EE
UT WOS:000294033800012
PM 21703943
ER
PT J
AU Moshkovich, N
Nisha, P
Boyle, PJ
Thompson, BA
Dale, RK
Lei, EP
AF Moshkovich, Nellie
Nisha, Parul
Boyle, Patrick J.
Thompson, Brandi A.
Dale, Ryan K.
Lei, Elissa P.
TI RNAi-independent role for Argonaute2 in CTCF/CP190 chromatin insulator
function
SO GENES & DEVELOPMENT
LA English
DT Article
DE RNAi; chromatin; insulator; Drosophila; ChIP-seq; nuclear organization
ID BITHORAX COMPLEX; HETEROCHROMATIN FORMATION; CHROMOSOME SEGREGATION;
GENOME ORGANIZATION; RESPONSE ELEMENTS; BOUNDARY-ELEMENT;
GENE-REGULATION; DISTINCT ROLES; GROUP PROTEINS; BINDING-SITES
AB A major role of the RNAi pathway in Schizosaccharomyces pombe is to nucleate heterochromatin, but it remains unclear whether this mechanism is conserved. To address this question in Drosophila, we performed genome-wide localization of Argonaute2 (AGO2) by chromatin immunoprecipitation (ChIP)-seq in two different embryonic cell lines and found that AGO2 localizes to euchromatin but not heterochromatin. This localization pattern is further supported by immunofluorescence staining of polytene chromosomes and cell lines, and these studies also indicate that a substantial fraction of AGO2 resides in the nucleus. Intriguingly, AGO2 colocalizes extensively with CTCF/CP190 chromatin insulators but not with genomic regions corresponding to endogenous siRNA production. Moreover, AGO2, but not its catalytic activity or Dicer-2, is required for CTCF/CP190-dependent Fab-8 insulator function. AGO2 interacts physically with CTCF and CP190, and depletion of either CTCF or CP190 results in genome-wide loss of AGO2 chromatin association. Finally, mutation of CTCF, CP190, or AGO2 leads to reduction of chromosomal looping interactions, thereby altering gene expression. We propose that RNAi-independent recruitment of AGO2 to chromatin by insulator proteins promotes the definition of transcriptional domains throughout the genome.
C1 [Moshkovich, Nellie; Nisha, Parul; Boyle, Patrick J.; Thompson, Brandi A.; Dale, Ryan K.; Lei, Elissa P.] NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
[Moshkovich, Nellie] Univ Maryland, Grad Program Mol & Cell Biol, College Pk, MD 20742 USA.
RP Lei, EP (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
EM leielissa@niddk.nih.gov
OI Dale, Ryan/0000-0003-2664-3744
FU National Institute of Diabetes and Digestive and Kidney Diseases
FX We thank A. Beyer for alpha-Pep; F. Fuller-Pace for alpha-p68; J. Kassis
for alpha-Pho; Q. Liu, A. Mueller, and M. Siomi for alpha-AGO2; P.
O'Farrell and D. Moazed for alpha-Pc; and C. Berg, J. Birchler, R.
Carthew, G. Gavalli, V. Corces, G. Hannon, S. Hou, F. Karch, J. Kassis,
E. Lai, G. Shanower, P. Schedl, and P. Zamore for strains. We are
indebted to P. Murphy for antibody characterization; M. Emmett for
primers; A. Dean for 3C protocols; S. Grewal, F. Karch, and B. Oliver
for discussions; and J. Kassis and L. Matzat for critical reading of the
manuscript. This work was supported by the Intramural Program of the
National Institute of Diabetes and Digestive and Kidney Diseases.
NR 65
TC 62
Z9 63
U1 1
U2 10
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 0890-9369
J9 GENE DEV
JI Genes Dev.
PD AUG 15
PY 2011
VL 25
IS 16
BP 1686
EP 1701
DI 10.1101/gad.16651211
PG 16
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA 808UF
UT WOS:000294003800005
PM 21852534
ER
PT J
AU Kulkarni, H
Okulicz, JF
Grandits, G
Crum-Cianflone, NF
Landrum, ML
Hale, B
Wortmann, G
Tramont, E
Polis, M
Dolan, M
Lifson, AR
Agan, BK
Ahuja, SK
Marconi, VC
AF Kulkarni, Hemant
Okulicz, Jason F.
Grandits, Greg
Crum-Cianflone, Nancy F.
Landrum, Michael L.
Hale, Braden
Wortmann, Glenn
Tramont, Edmund
Polis, Michael
Dolan, Matthew
Lifson, Alan R.
Agan, Brian K.
Ahuja, Sunil K.
Marconi, Vincent C.
TI Early Postseroconversion CD4 Cell Counts Independently Predict CD4 Cell
Count Recovery in HIV-1-Postive Subjects Receiving Antiretroviral
Therapy
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE CD4 count; highly active antiretroviral therapy; outcomes; predictors;
treatment response
ID PLASMA HIV RNA; VIROLOGICAL RESPONSES; HIV-1-INFECTED PATIENTS;
IMMUNOLOGICAL RESPONSE; DISEASE PROGRESSION; PROTEASE INHIBITOR;
INFECTED PATIENTS; IMMUNODEFICIENCY; SUPPRESSION; INTERRUPTION
AB Background: The relationship between CD4(+) T-cell counts determined soon after seroconversion with HIV-1 (baseline CD4), nadir CD4, and CD4 levels attained during highly active antiretroviral therapy (HAART) is unknown.
Methods: Longitudinal, including baseline (at or soon after HIV diagnosis), intermediate (nadir), and distal (post-HAART) CD4(+) T-cell counts were assessed in 1085 seroconverting subjects who achieved viral load suppression from a large well-characterized cohort. The association of baseline with post-HAART CD4(+) T-cell count was determined after adjustment for other relevant covariates.
Results: A higher baseline CD4(+) T-cell count predicted a greater postHAART CD4(+) T-cell count, independent of the nadir and other explanatory variables. Together, baseline and nadir strongly predicted the post-HAART CD4(+) count such that a high baseline and lower nadir were associated with a maximal immune recovery after HAART. Likelihood of recovery of the baseline count after HAART was significantly higher when the nadir/ baseline count ratio was consistently >= 0.6.
Conclusions: Among viral load suppressing seroconverters, the absolute CD4(+) T-cell count attained post-HAART is highly dependent on both baseline and nadir CD4(+) T-cell counts. These associations further support the early diagnosis and initiation of HAART among HIV-infected persons.
C1 [Kulkarni, Hemant; Ahuja, Sunil K.] S Texas Vet Hlth Care Syst, Vet Adm Res Ctr AIDS & HIV Infect 1, San Antonio, TX USA.
[Kulkarni, Hemant; Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.
[Okulicz, Jason F.; Grandits, Greg; Crum-Cianflone, Nancy F.; Landrum, Michael L.; Hale, Braden; Wortmann, Glenn; Tramont, Edmund; Polis, Michael; Agan, Brian K.; Marconi, Vincent C.] Uniformed Serv Univ Hlth Sci, Infect Dis Clin Res Program, Bethesda, MD 20814 USA.
[Okulicz, Jason F.; Landrum, Michael L.] Brooke Army Med Ctr, San Antonio Mil Med Ctr, Infect Dis Serv, Ft Sam Houston, TX 78234 USA.
[Grandits, Greg] Univ Minnesota, Div Biostat, Minneapolis, MN USA.
[Crum-Cianflone, Nancy F.; Hale, Braden] USN, Infect Dis Clin, San Diego Med Ctr, San Diego, CA 92152 USA.
[Wortmann, Glenn] Walter Reed Army Med Ctr, Infect Dis Serv, Washington, DC 20307 USA.
[Tramont, Edmund; Polis, Michael] NIAID, NIH, Bethesda, MD 20892 USA.
[Dolan, Matthew] Wilford Hall USAF Med Ctr, Henry M Jackson Fdn, Lackland AFB, TX 78236 USA.
[Lifson, Alan R.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol & Biochem, San Antonio, TX 78229 USA.
[Marconi, Vincent C.] Emory Univ, Sch Med, Dept Med, Div Infect Dis, Atlanta, GA USA.
RP Kulkarni, H (reprint author), 12023 Waterway Rdg, San Antonio, TX USA.
EM kulkarnih@uthscsa.edu
RI Marconi, Vincent/N-3210-2014;
OI Marconi, Vincent/0000-0001-8409-4689; Polis,
Michael/0000-0002-9151-2268; Agan, Brian/0000-0002-5114-1669
FU Infectious Disease Clinical Research Program (IDCRP) [IDCRP-000-03];
Department of Defense; National Institute of Allergy and Infectious
Diseases, National Institutes of Health (NIH) [Y1-AI-5072]; Veterans
Administration Center on AIDS and HIV infection of the South Texas
Veterans Health Care System; NIH [R37046326]; VA MERIT award; Elizabeth
Glaser Scientist Award; Burroughs Wellcome Clinical Scientist Award in
Translational Research; Doris Duke Distinguished Clinical Scientist
Award
FX Support for this work (IDCRP-000-03) was provided by the Infectious
Disease Clinical Research Program (IDCRP), a Department of Defense
program executed through the Uniformed Services University of the Health
Sciences. This project has been funded in whole, or in part, with
federal funds from the National Institute of Allergy and Infectious
Diseases, National Institutes of Health (NIH), under Inter-Agency
Agreement Y1-AI-5072. This work was also supported by the Veterans
Administration Center on AIDS and HIV infection of the South Texas
Veterans Health Care System, and a MERIT (R37046326) award from the NIH
to S. K. A. S. K. A. is also supported by a VA MERIT award and is a
recipient of the Elizabeth Glaser Scientist Award, the Burroughs
Wellcome Clinical Scientist Award in Translational Research, and the
Doris Duke Distinguished Clinical Scientist Award. The content of this
publication is the sole responsibility of the authors and does not
necessarily reflect the views or policies of the NIH or the Department
of Health and Human Services, the Department of Defense or the
Departments of the Army, Navy or Air Force. Mention of trade names,
commercial products, or organizations does not imply endorsement by the
US Government.
NR 45
TC 9
Z9 9
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD AUG 15
PY 2011
VL 57
IS 5
BP 387
EP 395
DI 10.1097/QAI.0b013e3182219113
PG 9
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 800RE
UT WOS:000293381300013
PM 21546844
ER
PT J
AU Jacobson, DL
Williams, P
Tassiopoulos, K
Melvin, A
Hazra, R
Farley, J
AF Jacobson, Denise L.
Williams, Paige
Tassiopoulos, Katherine
Melvin, Ann
Hazra, Rohan
Farley, John
TI Clinical Management and Follow-up of Hypercholesterolemia Among
Perinatally HIV-Infected Children Enrolled in the PACTG 219C Study
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE HIV; children; hypercholesterolemia; antiretroviral therapy; cohort
study
ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; CONTAINING ANTIRETROVIRAL THERAPY;
PROTEASE INHIBITOR SUBSTITUTION; INSULIN-RESISTANCE; SERUM-LIPIDS;
RISK-FACTORS; DYSLIPIDEMIA; HYPERLIPIDEMIA; IMPROVEMENT; ATAZANAVIR
AB Background: Hypercholesterolemia is common in perinatally HIV-infected (HIV+) children, but little is known about the clinical course and management in this population.
Methods: We studied HIV+ children in a multisite prospective cohort study (Pediatric AIDS Clinical Trials Group 219C) and considered follow-up for 2 years after development of hypercholesterolemia. We estimated the time and factors associated with resolution of hypercholesterolemia and described changes in antiretroviral regimen and use of lipid-lowering medications. We defined incident hypercholesterolemia as entry total cholesterol (cholesterol) <220 mg/dL and 2 subsequent consecutive cholesterol >= 220 mg/dL and defined resolution of hypercholesterolemia as 2 consecutive cholesterol <200 mg/dL after incident hypercholesterolemia.
Results: Among 240 incident hypercholesterolemia cases, 81 (34%) had resolution to normal cholesterol within 2 years of follow-up (median follow-up = 1.9 years). The median age of cases was 10.3 years with 54% non-Hispanic black and 53% male. Resolution to normal cholesterol was more likely in children who changed antiretroviral regimen (adjusted hazard ratio = 2.37, 95% confidence interval: 1.45 to 3.88) and who were 13 years and older (aHR = 2.39, 95% confidence interval: 1.33 to 4.27). Types of regimen changes varied greatly, and 15 children began statins.
Conclusion: The majority of children who develop hypercholesterolemia maintain elevated levels over time, potentially placing them at risk for premature cardiovascular morbidity.
C1 [Jacobson, Denise L.] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Williams, Paige] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Tassiopoulos, Katherine] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Melvin, Ann] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA.
[Hazra, Rohan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Farley, John] Univ Maryland, Sch Med, Dept Pediat, Baltimore, MD 21201 USA.
RP Jacobson, DL (reprint author), Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, 651 Huntington Ave, Boston, MA 02115 USA.
EM jacobson@sdac.harvard.edu
FU Statistical and Data Analysis Center at Harvard School of Public Health,
under the National Institute of Allergy and Infectious Diseases [5 U01
AI41110]; PACTG; International Maternal Pediatric Adolescent AIDS
Clinical Trials Group; National Institute of Allergy and Infectious
Diseases; Eunice Kennedy Shriver National Institute of Child Health and
Human Development [N01-DK-9-001/HHSN267200800001C]; [1 U01 AI068616]
FX Supported by the Statistical and Data Analysis Center at Harvard School
of Public Health, under the National Institute of Allergy and Infectious
Diseases cooperative agreement No. 5 U01 AI41110 with the PACTG and No.
1 U01 AI068616 with the International Maternal Pediatric Adolescent AIDS
Clinical Trials Group. Support of the sites was provided by the National
Institute of Allergy and Infectious Diseases and the Eunice Kennedy
Shriver National Institute of Child Health and Human Development;
International and Domestic Pediatric and Maternal HIV Clinical Trials
Network funded by the Eunice Kennedy Shriver National Institute of Child
Health and Human Development (contract number
N01-DK-9-001/HHSN267200800001C).; We thank the children and families for
their participation in PACTG 219C and the individuals and institutions
involved in the conduct of 219C and the leadership and participants of
the P219/219C protocol team. Overall support for the International
Maternal Pediatric Adolescent AIDS Clinical Trials Group was provided by
the National Institute of Allergy and Infectious Diseases (U01
AI068632), the Eunice Kennedy Shriver National Institute of Child Health
and Human Development, and the National Institute of Mental Health
(AI068632). We also thank the individual staff members and sites who
have participated in the conduct of this study, as provided in
Supplemental Digital Content 1 (see Appendix,
http://links.lww.com/QAI/A191). We thank Todd Brown, MD, PhD, for
clinical information used to develop this article.
NR 35
TC 11
Z9 11
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD AUG 15
PY 2011
VL 57
IS 5
BP 413
EP 420
DI 10.1097/QAI.0b013e31822203f5
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 800RE
UT WOS:000293381300016
PM 21602698
ER
PT J
AU Shinohara, RT
Crainiceanu, CM
Caffo, BS
Gaitan, MI
Reich, DS
AF Shinohara, Russell T.
Crainiceanu, Ciprian M.
Caffo, Brian S.
Gaitan, Maria Ines
Reich, Daniel S.
TI Population-wide principal component-based quantification of
blood-brain-barrier dynamics in multiple sclerosis
SO NEUROIMAGE
LA English
DT Article
DE Blood-brain barrier; Multiple sclerosis; MRI; DCE-MRI; Gadolinium
enhancement; Functional principal components analysis
AB The processes by which new white matter lesions in multiple sclerosis (MS) develop are only partially understood. Much of this understanding has come through magnetic resonance imaging (MRI) of the human brain. One of the hallmarks of new lesion development in MS is enhancement on T-1-weighted MRI scans following the intravenous administration of a gadolinium-based contrast agent that shortens the longitudinal relaxation time of the tissue. Visible enhancement on the MRI results from the opening of the blood-brain barrier and reveals areas of active inflammation. The incidence and number of existing enhancing lesions are common outcome measures used in MS treatment clinical trials. Dynamic-contrast-enhanced MRI (DCE-MRI) can estimate the rate at which contrast agents pass from the plasma to MS lesions. In this paper, we develop a principal component-based framework for the analysis of these data that provides biologically meaningful quantification of blood-brain-barrier opening in new MS lesions. To accomplish this, we use functional principal components analysis to study directions of variation in the voxel-level time series of intensities both within and across subjects. The analysis reveals and allows quantification of typical spatiotemporal enhancement patterns in acute MS lesions, providing measures of magnitude, rate, shape (ring-like vs. nodular), and dynamics (centrifugal vs. centripetal). Across 10 subjects with relapsing-remitting and primary progressive MS, we found subjects to have between 0 and 12 gadolinium-enhancing lesions, the majority of which enhanced centripetally. We quantified the spatiotemporal behavior within each of these lesions using novel measures. Further application of these techniques will determine the extent to which these lesion measures can predict or track response to therapy or long-term prognosis in this disorder. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Shinohara, Russell T.; Crainiceanu, Ciprian M.; Caffo, Brian S.] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA.
[Gaitan, Maria Ines; Reich, Daniel S.] Natl Inst Neurol Disorders & Stroke, Translat Neuroradiol Unit, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
RP Shinohara, RT (reprint author), Johns Hopkins Univ, Dept Biostat, 615 N Wolfe St, Baltimore, MD 21205 USA.
EM rshinoha@jhsph.edu
RI Reich, Daniel/E-5701-2010
OI Reich, Daniel/0000-0002-2628-4334
FU National Institute of Neurological Disorders and Stroke; National
Institute of Neurological Disorders And Stroke [R01NS060910]; National
Institute on Aging [T32AG000247]; NIH National Institute of Biomedical
Imaging and Bioengineering [EB012547]
FX The authors thank Bibiana Bielekova, Iordanis Evangelou, Colin Shea,
Roger Stone, the Neuroimmunology Branch clinical group, and the NIH
Functional Magnetic Resonance Imaging Facility technologists, who were
instrumental in collecting and processing the data for this study. The
research was partially supported by the Intramural Research Program of
the National Institute of Neurological Disorders and Stroke. The
research of Shinohara, Crainiceanu and Caffo was supported by Award
Number R01NS060910 from the National Institute of Neurological Disorders
And Stroke. Shinohara is supported by the Epidemiology and Biostatistics
of Aging Training Grant T32AG000247 from the National Institute on
Aging. Crainiceanu and Caffo are partially supported by EB012547 from
the NIH National Institute of Biomedical Imaging and Bioengineering. The
content is solely the responsibility of the authors and does not
necessarily represent the official views of the funding agencies.
NR 18
TC 14
Z9 14
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD AUG 15
PY 2011
VL 57
IS 4
BP 1430
EP 1446
DI 10.1016/j.neuroimage.2011.05.038
PG 17
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 796LZ
UT WOS:000293054100016
PM 21635955
ER
PT J
AU Raznahan, A
Greenstein, D
Lee, Y
Long, R
Clasen, L
Gochman, P
Addington, A
Giedd, JN
Rapoport, JL
Gogtay, N
AF Raznahan, Armin
Greenstein, Deanna
Lee, Yohan
Long, Robert
Clasen, Liv
Gochman, Pete
Addington, Anjene
Giedd, Jay N.
Rapoport, Judith L.
Gogtay, Nitin
TI Catechol-o-methyl transferase (COMT) val(158)met polymorphism and
adolescent cortical development in patients with childhood-onset
schizophrenia, their non-psychotic siblings, and healthy controls
SO NEUROIMAGE
LA English
DT Article
DE Neuroimaging; COMT; Schizophrenia; Siblings; Cortex; Maturation;
Dopamine
ID HUMAN CEREBRAL-CORTEX; BRAIN-DEVELOPMENT; YOUNG-ADULTS; VAL158MET
POLYMORPHISM; INTELLECTUAL ABILITY; EXECUTIVE FUNCTION;
GENETIC-VARIATION; BIPOLAR DISORDER; MRI DATA; METHYLTRANSFERASE
AB Non-psychotic individuals at increased risk for schizophrenia show alterations in fronto-striatal dopamine signaling and cortical gray matter maturation reminiscent of those seen in schizophrenia. It remains unclear however if variations in dopamine signaling influence rates of structural cortical maturation in typically developing individuals, and whether such influences are disrupted in patients with schizophrenia and their non-psychotic siblings. We sought to address these issues by relating a functional Val -> Met polymorphism within the gene encoding catechol-o-methyltransferase (COMT)-a key enzymatic regulator of cortical dopamine levels-to longitudinal structural neuroimaging measures of cortical gray matter thickness. We included a total of 792 magnetic resonance imaging brain scans, acquired between ages 9 and 22 years from patients with childhood-onset schizophrenia (COS), their non-psychotic full siblings, and matched healthy controls. Whereas greater Val allele dose (which confers enhanced dopamine catabolism and is proposed to aggravate cortical deficits in schizophrenia) accelerated adolescent cortical thinning in both schizophrenia probands and their siblings, it attenuated cortical thinning in healthy controls. This similarity between COS patients and their siblings was accompanied by differences between the two groups in the timing and spatial distribution of disrupted COMT influences on cortical maturation. Consequently, whereas greater Val "dose" conferred persistent dorsolateral prefrontal cortical deficits amongst affected probands by adulthood, cortical thickness differences associated with varying Val dose in non-psychotic siblings resolved over the age-range studied. These findings suggest that cortical abnormalities in pedigrees affected by schizophrenia may be contributed to by a disruption of dopaminergic infleunces on cortical maturation. (C) 2011 Published by Elsevier Inc.
C1 [Raznahan, Armin] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA.
[Raznahan, Armin] Kings Coll London, Dept Child & Adolescent Psychiat, Inst Psychiat, London, England.
RP Raznahan, A (reprint author), NIMH, Child Psychiat Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM raznahan@mail.nih.gov
RI Giedd, Jay/A-3080-2008; Gogtay, Nitin/A-3035-2008; Raznahan,
Armin/F-4534-2012; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015
OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978
FU National Institutes of Health, National Institute of Health Intramural
Research; UK Medical Research Council [AR-G0701370]
FX This study was funded through the National Institutes of Health,
National Institute of Health Intramural Research, and a UK Medical
Research Council Clinical Research Training Fellowship (Author
AR-G0701370). The authors wish to thank the participants who took part
in this study.
NR 63
TC 30
Z9 31
U1 0
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD AUG 15
PY 2011
VL 57
IS 4
BP 1517
EP 1523
DI 10.1016/j.neuroimage.2011.05.032
PG 7
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 796LZ
UT WOS:000293054100024
PM 21620981
ER
PT J
AU Lezin, G
Kosaka, Y
Yost, HJ
Kuehn, MR
Brunelli, L
AF Lezin, George
Kosaka, Yasuhiro
Yost, H. Joseph
Kuehn, Michael R.
Brunelli, Luca
TI A One-Step Miniprep for the Isolation of Plasmid DNA and Lambda Phage
Particles
SO PLOS ONE
LA English
DT Article
ID ESCHERICHIA-COLI; DEOXYRIBONUCLEIC-ACID; BACTERIAL PLASMIDS; RAPID
PREPARATION; CIRCULAR DNA; LYSIS; DETERGENTS
AB Plasmid DNA minipreps are fundamental techniques in molecular biology. Current plasmid DNA minipreps use alkali and the anionic detergent SDS in a three-solution format. In addition, alkali minipreps usually require additional column-based purification steps and cannot isolate other extra-chromosomal elements, such as bacteriophages. Non-ionic detergents (NIDs) have been used occasionally as components of multiple-solution plasmid DNA minipreps, but a one-step approach has not been developed. Here, we have established a one-tube, one-solution NID plasmid DNA miniprep, and we show that this approach also isolates bacteriophage lambda particles. NID minipreps are more time-efficient than alkali minipreps, and NID plasmid DNA performs better than alkali DNA in many downstream applications. In fact, NID crude lysate DNA is sufficiently pure to be used in digestion and sequencing reactions. Microscopic analysis showed that the NID procedure fragments E. coli cells into small protoplast-like components, which may, at least in part, explain the effectiveness of this approach. This work demonstrates that one-step NID minipreps are a robust method to generate high quality plasmid DNA, and NID approaches can also isolate bacteriophage lambda particles, outperforming current standard alkali-based minipreps.
C1 [Lezin, George; Kosaka, Yasuhiro; Brunelli, Luca] Univ Utah, Sch Med, Dept Pediat, Div Neonatol, Salt Lake City, UT 84112 USA.
[Yost, H. Joseph] Univ Utah, Sch Med, Dept Neurobiol & Anat, Salt Lake City, UT USA.
[Kuehn, Michael R.] NCI, Lab Prot Dynam & Signaling, NIH, Frederick, MD 21701 USA.
RP Lezin, G (reprint author), Univ Utah, Sch Med, Dept Pediat, Div Neonatol, Salt Lake City, UT 84112 USA.
EM mkuehn@mail.nih.gov; luca.brunelli@genetics.utah.edu
RI Kuehn, Michael/A-4573-2014
OI Kuehn, Michael/0000-0002-7703-9160
FU Division of Neonatology, the Children's Health Research Center; Primary
Children's Medical Center Foundation; Department of Pediatrics, The
University of Utah School of Medicine; American Heart Association;
Western States Affiliate [09BGIA2251076]; National Institutes of Health,
National Cancer Institute, and Center for Cancer Research
FX This work was supported by funds to L.B. from the Division of
Neonatology, the Children's Health Research Center, and the Primary
Children's Medical Center Foundation Innovative Grant, Department of
Pediatrics, The University of Utah School of Medicine, and the American
Heart Association, Beginning Grant-In-Aid, Western States Affiliate
(09BGIA2251076); and by funds to M.R.K. from the Intramural Research
Program of the National Institutes of Health, National Cancer Institute,
and Center for Cancer Research. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services and nor does mention of trade names, commercial
products or organizations imply endorsement by the U.S. Government. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 36
TC 1
Z9 2
U1 4
U2 26
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 15
PY 2011
VL 6
IS 8
AR e23457
DI 10.1371/journal.pone.0023457
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 808CV
UT WOS:000293953700025
PM 21858126
ER
PT J
AU Deroo, LA
Cummings, P
Mueller, BA
AF DeRoo, Lisa A.
Cummings, Peter
Mueller, Beth A.
TI Smoking Before the First Pregnancy and the Risk of Breast Cancer: A
Meta-Analysis
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Review
DE breast neoplasms; pregnancy; smoking
ID PASSIVE CIGARETTE-SMOKING; NAT2 ACETYLATION GENOTYPE; UNITED-STATES;
TOBACCO-SMOKE; YOUNG-WOMEN; NULL ASSOCIATION; NURSES HEALTH; REGISTRY
DATA; EXPOSURE; BIAS
AB The authors conducted a meta-analysis of the association between smoking before a first pregnancy, when undifferentiated breast tissue may be vulnerable to tobacco carcinogens, and the risk of breast cancer. A search of the published literature through August 2010 identified 23 papers reporting on associations between smoking before a first pregnancy and breast cancer. Odds ratios or hazard ratios and 95% confidence intervals, adjusted for known or suspected breast cancer risk factors, were abstracted from each study. Data were pooled using both fixed- and random-effects models. The fixed-effect summary risk ratio for breast cancer among the women who smoked before their first pregnancy versus women who had never smoked was 1.10 (95% confidence interval: 1.07, 1.14); the random-effects estimate was similar. The separate fixed-effect risk ratios for smoking only before the first pregnancy (5 studies) or only after the first pregnancy (16 studies) were both 1.07, providing no evidence that breast tissue is more susceptible to malignant transformation from smoking before the first pregnancy. While these small summary risk ratios may represent causal effects, residual confounding could readily produce estimates of this size in the absence of any causal effect.
C1 [DeRoo, Lisa A.; Mueller, Beth A.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[DeRoo, Lisa A.; Cummings, Peter; Mueller, Beth A.] Univ Washington, Dept Epidemiol, Sch Publ Hlth, Seattle, WA 98195 USA.
RP Deroo, LA (reprint author), NIEHS, Epidemiol Branch, POB 12233,MD A3-05,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM DeRooL@niehs.nih.gov
NR 49
TC 18
Z9 18
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 AUG 15
PY 2011
VL 174
IS 4
BP 390
EP 402
DI 10.1093/aje/kwr090
PG 13
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 803QH
UT WOS:000293595300002
PM 21719745
ER
PT J
AU Venzo, A
Antonello, S
Gascon, JA
Guryanov, I
Leapman, RD
Perera, NV
Sousa, A
Zamuner, M
Zanella, A
Maran, F
AF Venzo, Alfonso
Antonello, Sabrina
Gascon, Jose A.
Guryanov, Ivan
Leapman, Richard D.
Perera, Neranjan V.
Sousa, Alioscka
Zamuner, Martina
Zanella, Alessandro
Maran, Flavio
TI Effect of the Charge State (z =-1, 0,+1) on the Nuclear Magnetic
Resonance of Monodisperse Au-25[S(CH2)(2)Ph](18)(z) Clusters
SO ANALYTICAL CHEMISTRY
LA English
DT Article
ID DISSOCIATIVE ELECTRON-TRANSFER; THIOLATE-PROTECTED AU-25; GOLD
NANOPARTICLE; CRYSTAL-STRUCTURE; REDOX POTENTIALS; AU-38 CLUSTERS;
SELF-EXCHANGE; ELECTROREDUCTION; RESOLUTION; ENERGIES
AB Monodisperse Au25L180 (L = S(CH2)(2)Ph) and [n-Oct(4)N(+)][Au25L18,(-)]clusters were synthesized in tetrahydrofuran. An original strategy was then devised to oxidize them: in the presence of bis(pentafluorobenzoyl) peroxide, the neutral or the negatively charged dusters react as efficient electron donors in a dissociative electron-transfer (ET) process, in the former case yielding [Au25L18+][C6F5CO2-]. As opposed to, other reported redox methods, this dissociative ET approach is irreversible, easily controllable, and clean, particularly for NMR purposes, as no hydrogen atoms are introduced. By using this approach, the -1, 0, and +1 charge states of Au25L18 could be fully characterized by H-1 and C-13 NMR spectroscopy, using one- and two-dimensional techniques, in various solvents, and as a function of temperature. For all charge states, the NMR results and analysis nicely match recent structural findings about the presence of two different ligand populations in the capping monolayer, each resonance of the two ligand families displaying distinct NMR patterns. The radical nature of Au25L180 is particularly evident in the H-1 and C-13 NMR patterns" of the inner ligands. The NMR behavior of radical (AuL180)-L-25 was also simulated by DFT calculations, and the interplay between theory and experiments revealed a fundamental paramagnetic contribution coming from Fermi contact shifts. Interestingly, the NMR patterns of Au25L18- and Au25L18+ were found to be quite similar, pointing to the latter duster form as a diamagnetic species.
C1 [Venzo, Alfonso; Antonello, Sabrina; Guryanov, Ivan; Zamuner, Martina; Zanella, Alessandro; Maran, Flavio] Univ Padua, Dept Chem, I-35131 Padua, Italy.
[Venzo, Alfonso] ISTM CNR, I-35131 Padua, Italy.
[Gascon, Jose A.; Perera, Neranjan V.] Univ Connecticut, Dept Chem, Storrs, CT 06269 USA.
[Leapman, Richard D.; Sousa, Alioscka] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA.
RP Maran, F (reprint author), Univ Padua, Dept Chem, Via Marzolo 1, I-35131 Padua, Italy.
EM flavio.maran@unipd.it
RI Guryanov, Ivan/A-6007-2012; Gascon, Joaquim/M-3598-2015; Guryanov,
Ivan/N-3117-2016; Gascon, Jose /N-5702-2016
OI Gascon, Joaquim/0000-0002-5045-1585; Guryanov, Ivan/0000-0001-6897-3528;
Gascon, Jose /0000-0002-4176-9030
FU Foundation CARIPARO
FX This work was financially supported by the Foundation CARIPARO.
NR 34
TC 55
Z9 55
U1 3
U2 57
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0003-2700
J9 ANAL CHEM
JI Anal. Chem.
PD AUG 15
PY 2011
VL 83
IS 16
BP 6355
EP 6362
DI 10.1021/ac2012653
PG 8
WC Chemistry, Analytical
SC Chemistry
GA 805WD
UT WOS:000293758800035
PM 21718063
ER
PT J
AU Fonseca, CG
Backhaus, M
Bluemke, DA
Britten, RD
Chung, JD
Cowan, BR
Dinov, ID
Finn, JP
Hunter, PJ
Kadish, AH
Lee, DC
Lima, JAC
Medrano-Gracia, P
Shivkumar, K
Suinesiaputra, A
Tao, WC
Young, AA
AF Fonseca, Carissa G.
Backhaus, Michael
Bluemke, David A.
Britten, Randall D.
Chung, Jae Do
Cowan, Brett R.
Dinov, Ivo D.
Finn, J. Paul
Hunter, Peter J.
Kadish, Alan H.
Lee, Daniel C.
Lima, Joao A. C.
Medrano-Gracia, Pau
Shivkumar, Kalyanam
Suinesiaputra, Avan
Tao, Wenchao
Young, Alistair A.
TI The Cardiac Atlas Project-an imaging database for computational modeling
and statistical atlases of the heart
SO BIOINFORMATICS
LA English
DT Article
ID HUMAN BRAIN; POPULATION; DESIGN; VOLUME
AB Motivation: Integrative mathematical and statistical models of cardiac anatomy and physiology can play a vital role in understanding cardiac disease phenotype and planning therapeutic strategies. However, the accuracy and predictive power of such models is dependent upon the breadth and depth of noninvasive imaging datasets. The Cardiac Atlas Project (CAP) has established a large-scale database of cardiac imaging examinations and associated clinical data in order to develop a shareable, web-accessible, structural and functional atlas of the normal and pathological heart for clinical, research and educational purposes. A goal of CAP is to facilitate collaborative statistical analysis of regional heart shape and wall motion and characterize cardiac function among and within population groups.
Results: Three main open-source software components were developed: (i) a database with web-interface; (ii) a modeling client for 3D + time visualization and parametric description of shape and motion; and (iii) open data formats for semantic characterization of models and annotations. The database was implemented using a three-tier architecture utilizing MySQL, JBoss and Dcm4chee, in compliance with the DICOM standard to provide compatibility with existing clinical networks and devices. Parts of Dcm4chee were extended to access image specific attributes as search parameters. To date, approximately 3000 de-identified cardiac imaging examinations are available in the database. All software components developed by the CAP are open source and are freely available under the Mozilla Public License Version 1.1 (http://www.mozilla.org/MPL/MPL-1.1.txt).
C1 [Backhaus, Michael; Britten, Randall D.; Chung, Jae Do; Cowan, Brett R.; Hunter, Peter J.; Medrano-Gracia, Pau; Suinesiaputra, Avan; Young, Alistair A.] Univ Auckland, Auckland Bioengn Inst, Auckland 1, New Zealand.
[Fonseca, Carissa G.; Finn, J. Paul; Tao, Wenchao] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol Sci, Los Angeles, CA 90095 USA.
[Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, NIH, Ctr Clin, Bethesda, MD 20814 USA.
[Dinov, Ivo D.] Univ Calif Los Angeles, Lab Neuro Imaging, Los Angeles, CA 90095 USA.
[Kadish, Alan H.; Lee, Daniel C.] Northwestern Univ, Div Cardiol, Feinberg Sch Med, Chicago, IL 60611 USA.
[Lima, Joao A. C.] Johns Hopkins Univ, Sch Med, Dept Radiol, Div Cardiol, Baltimore, MD 21205 USA.
[Shivkumar, Kalyanam] Univ Calif Los Angeles, David Geffen Sch Med, UCLA Cardiac Arrhythmia Ctr, Los Angeles, CA 90095 USA.
RP Young, AA (reprint author), Univ Auckland, Auckland Bioengn Inst, 70 Symonds St, Auckland 1, New Zealand.
EM a.young@auckland.ac.nz
RI Trivedi, Kruti/E-7558-2015;
OI Shivkumar, Kalyanam/0000-0002-4121-1766; Hunter,
Peter/0000-0001-9665-4145; Dinov, Ivo/0000-0003-3825-4375; Bluemke,
David/0000-0002-8323-8086; Suinesiaputra, Avan/0000-0003-1165-458X;
Young, Alistair/0000-0001-5702-4220; Lee, Daniel/0000-0001-9447-4175;
Medrano-Gracia, Pau/0000-0002-6255-4864
FU National Heart, Lung and Blood Institute, USA [R01HL087773]; National
Institutes of Health/National Center for Research Resources [U54
RR021813, P41 RR013642]; St Jude Medical, Inc; National Heart, Lung and
Blood Institute [R01HL91069, N01-HC-95169]
FX National Heart, Lung and Blood Institute, USA (R01HL087773). Support
from the Center for Computational Biology (LONI) was provided by
National Institutes of Health/National Center for Research Resources
(U54 RR021813, P41 RR013642). MESA was supported by the National Heart,
Lung and Blood Institute (N01-HC-95159 through N01-HC-95169). A full
list of participating MESA investigators and institutions can be found
at http://www.mesa-nhlbi.org. DETERMINE was supported by St Jude
Medical, Inc; and the National Heart, Lung and Blood Institute
(R01HL91069). A list of participating DETERMINE investigators can be
found at http://www.clinicaltrials.gov. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Heart, Lung and Blood Institute or the
National Institutes of Health.
NR 31
TC 67
Z9 67
U1 0
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
J9 BIOINFORMATICS
JI Bioinformatics
PD AUG 15
PY 2011
VL 27
IS 16
BP 2288
EP 2295
DI 10.1093/bioinformatics/btr360
PG 8
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 803ZC
UT WOS:000293620800016
PM 21737439
ER
PT J
AU Hagemann, AR
Cadungog, M
Hagemann, IS
Hammond, R
Adams, SF
Chu, CS
Rubin, SC
Zhang, L
Addya, K
Birrer, MJ
Gimotty, PA
Coukos, G
AF Hagemann, Andrea R.
Cadungog, Mark
Hagemann, Ian S.
Hammond, Rachel
Adams, Sarah F.
Chu, Christina S.
Rubin, Stephen C.
Zhang, Lin
Addya, Kathakali
Birrer, Michael J.
Gimotty, Phyllis A.
Coukos, George
TI Tissue-based immune monitoring I Tumor core needle biopsies allow
in-depth interrogation of the tumor microenvironment
SO CANCER BIOLOGY & THERAPY
LA English
DT Article
DE ovarian neoplasms; lymphocytes; tumor-infiltrating; adoptive
immunotherapy; gene expression profiling; immunohistochemistry
ID INTRAEPITHELIAL T-CELLS; OVARIAN-CANCER; INFILTRATING LYMPHOCYTES;
PROGNOSTIC-SIGNIFICANCE; COLORECTAL-CANCER; CARCINOMA; SURVIVAL;
RESPONSES; STAGE; IMMUNOTHERAPY
AB We sought to assess the feasibility and reproducibility of performing tissue-based immune characterization of the tumor microenvironment using CT-compatible needle biopsy material. Three independent biopsies were obtained intraoperatively from one metastatic epithelial ovarian cancer lesion of seven consecutive patients undergoing surgical cytoreduction using a 16-gauge core biopsy needle. Core specimens were snap-frozen and subjected to immunohistochemistry (IHC) against human CD3, CD4, CD8 and FoxP3. A portion of the cores was used to isolate RNA for (1) real-time quantitative (q) PCR for CD3, CD4, CD8, FoxP3, IL-10 and TGF beta, (2) multiplexed PCR-based T-cell receptor (TCR) CDR3 V-beta region spectratyping and (3) gene expression profiling. Pearson's correlations were examined for immunohistochemistry and PCR gene expression, as well as for gene expression array data obtained from different tumor biopsies. Needle biopsy yielded sufficient tissue for all assays in all patients. IHC was highly reproducible and informative. Significant correlations were seen between the frequency of CD3+, CD8+ and FoxP3+ T cells by IHC with CD3-epsilon, CD8A and FoxP3 gene expression, respectively, by qPCR (r = 0.61, 0.86 and 0.89; all p < 0.05). CDR3 spectratyping was feasible and highly reproducible in each tumor, and indicated a restricted repertoire for specific TCR V-beta chains in tumor-infiltrating T cells. Microarray gene expression revealed strong correlation between different biopsies collected from the same tumor. Our results demonstrate a feasible and reproducible method of immune monitoring using CT-compatible needle biopsies from tumor tissue, thereby paving the way for sophisticated translational studies during tumor biological therapy.
C1 [Hagemann, Andrea R.; Cadungog, Mark; Adams, Sarah F.; Chu, Christina S.; Rubin, Stephen C.; Zhang, Lin; Coukos, George] Univ Penn, Ovarian Canc Res Ctr, Philadelphia, PA 19104 USA.
[Hagemann, Andrea R.; Cadungog, Mark; Adams, Sarah F.; Chu, Christina S.; Rubin, Stephen C.; Zhang, Lin; Coukos, George] Univ Penn, Div Gynecol Oncol, Philadelphia, PA 19104 USA.
[Hagemann, Ian S.; Addya, Kathakali] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Hammond, Rachel; Gimotty, Phyllis A.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Birrer, Michael J.] NCI, Cell & Canc Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Coukos, G (reprint author), Univ Penn, Ovarian Canc Res Ctr, Philadelphia, PA 19104 USA.
EM gcks@mail.med.upenn.edu
FU Ovarian Cancer SPORE NIH [P50-CA083638]; Ovarian Cancer Research
Foundation
FX This work was supported by Ovarian Cancer SPORE NIH P50-CA083638 and the
Ovarian Cancer Research Foundation.
NR 29
TC 5
Z9 5
U1 0
U2 4
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4047
J9 CANCER BIOL THER
JI Cancer Biol. Ther.
PD AUG 15
PY 2011
VL 12
IS 4
BP 357
EP 366
DI 10.4161/cbt.12.4.16951
PG 10
WC Oncology
SC Oncology
GA 806WN
UT WOS:000293847500012
PM 21785264
ER
PT J
AU Hagemann, AR
Hagemann, IS
Cadungog, M
Hwang, WT
Patel, P
Lal, P
Hammond, R
Gimotty, PA
Chu, CS
Rubin, SC
Birrer, MJ
Powell, DJ
Feldman, MD
Coukos, G
AF Hagemann, Andrea R.
Hagemann, Ian S.
Cadungog, Mark
Hwang, Wei-Ting
Patel, Priya
Lal, Priti
Hammond, Rachel
Gimotty, Phyllis A.
Chu, Christina S.
Rubin, Stephen C.
Birrer, Michael J.
Powell, Daniel J., Jr.
Feldman, Michael D.
Coukos, George
TI Tissue-based immune monitoring II Multiple tumor sites reveal
immunologic homogeneity in serous ovarian carcinoma
SO CANCER BIOLOGY & THERAPY
LA English
DT Article
DE ovarian neoplasms; lymphocytes; tumor-infiltrating; adoptive
immunotherapy; metastasis; microarray analysis
ID REGULATORY T-CELLS; LYMPHOCYTE-ASSOCIATED ANTIGEN-4; DENDRITIC CELLS;
INFILTRATING LYMPHOCYTES; ANTIBODY BLOCKADE; CANCER-PATIENTS; SURVIVAL;
STAGE; IMMUNOTHERAPY; PROGNOSIS
AB The presence of tumor-infiltrating lymphocytes (TILs) in epithelial ovarian cancer indicates a host antitumor response and is associated with improved survival. We wished to determine the extent to which TIL density differs from site to site within a given patient. We initially studied multiple paired metastases from serous ovarian carcinoma obtained at the time of primary debulking. The expression of genes in specific immune-related pathways was profiled on a pilot set of five patients. We then used immunohistochemistry and quantitative PCR to estimate the density of CD3(+), CD8(+) and FoxP3(+) TILs in these same tumors. To extend the findings to a larger cohort, we semiquantitatively measured intraepithelial and stromal TILs in a tissue microarray (TMA) containing both primary tumors and metastases from 50 patients. In the pilot group, genes related to antimicrobial signaling and TGF beta signaling showed between-site heterogeneity, whereas cytokines and antigen presentation transcripts were more homogeneous in any given patient. IHC and qPCR for T-cell markers were concordant. In the TMA cohort, two-way ANOVA showed that TIL heterogeneity between sites was present in some but not all patients. The stroma of extra-ovarian metastases showed significantly greater TIL infiltration than ovarian sites. A simulation showed that at clinically meaningful levels of precision, up to 3% of patients will be misclassified for intraepithelial TILs by a single biopsy. In conclusion, between-site heterogeneity exists in some patients with metastatic serous ovarian cancer. The predictive value of biopsies should be considered in clinical trial design.
C1 [Hagemann, Andrea R.; Cadungog, Mark; Patel, Priya; Chu, Christina S.; Rubin, Stephen C.; Powell, Daniel J., Jr.; Coukos, George] Univ Penn, Ovarian Canc Res Ctr, Philadelphia, PA 19104 USA.
[Hagemann, Andrea R.; Cadungog, Mark; Patel, Priya; Chu, Christina S.; Rubin, Stephen C.; Powell, Daniel J., Jr.; Coukos, George] Univ Penn, Div Gynecol Oncol, Philadelphia, PA 19104 USA.
[Hagemann, Ian S.; Lal, Priti; Powell, Daniel J., Jr.; Feldman, Michael D.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Hwang, Wei-Ting; Hammond, Rachel; Gimotty, Phyllis A.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Birrer, Michael J.] NCI, Cell & Canc Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Coukos, G (reprint author), Univ Penn, Ovarian Canc Res Ctr, Philadelphia, PA 19104 USA.
EM gcks@mail.med.upenn.edu
FU Ovarian Cancer SPORE NIH [P50-CA083638]; Ovarian Cancer Research
Foundation; NCI [P30 CA016520-34]
FX We thank Li-Ping Wang and Emma Hung for outstanding technical support
with TMA construction and immunostaining. This work was supported by
Ovarian Cancer SPORE NIH P50-CA083638, the Ovarian Cancer Research
Foundation and a core grant (NCI P30 CA016520-34) to the Abramson Cancer
Center of the University of Pennsylvania.
NR 33
TC 7
Z9 7
U1 0
U2 2
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4047
J9 CANCER BIOL THER
JI Cancer Biol. Ther.
PD AUG 15
PY 2011
VL 12
IS 4
BP 367
EP 377
DI 10.4161/cbt.12.4.16908
PG 11
WC Oncology
SC Oncology
GA 806WN
UT WOS:000293847500013
PM 21785280
ER
PT J
AU Dugan, VG
Dunham, EJ
Jin, GZ
Sheng, ZM
Kaser, E
Nolting, JM
Alexander, HL
Slemons, RD
Taubenberger, JK
AF Dugan, Vivien G.
Dunham, Eleca J.
Jin, Guozhong
Sheng, Zong-Mei
Kaser, Emilee
Nolting, Jacqueline M.
Alexander, H. Lloyd, Jr.
Slemons, Richard D.
Taubenberger, Jeffery K.
TI Phylogenetic analysis of low pathogenicity H5N1 and H7N3 influenza A
virus isolates recovered from sentinel, free flying, wild mallards at
one study site during 2006
SO VIROLOGY
LA English
DT Article
DE Influenza A virus; Avian influenza; H5N1; H7N3; Phylogenetics
ID AVIAN INFLUENZA; NORTH-AMERICA; PANDEMIC INFLUENZA; SEQUENCE-ANALYSIS;
UNITED-STATES; BIRDS; EVOLUTION; POULTRY; DUCKS; EPIDEMIOLOGY
AB From August 2 to October 11, 2006, clusters of low pathogenicity (LP) North American lineage H5N1 and H7N3 avian influenza A viruses (AIV), and other subtypes, were recovered from free-flying, resident, wild mallards used as sentinels at one site. The antigenic subtypes, pathogenicity potential, and Sanger sequencing of the isolates determined the H5N1 and H7N3 isolates were only recovered from samples collected on 8/2/2006 and 9/8/2006, respectively. However, subsequent efforts using next-generation sequencing (NGS) and additional Sanger sequencing found partial H7 segments in other HA-NA virus combinations on 8/2/2006, 9/8/2006 and 10/11/2006. It is well established that over larger geographic areas and years AIVs form transient genomic constellations; this sequential sampling data revealed that over a short period of time the dynamics of AIVs can be active and newer sequencing platforms increase recognition of mixed infections. Both findings provide further insight into the natural history of AIVs in natural reservoirs. Published by Elsevier Inc.
C1 [Dugan, Vivien G.; Dunham, Eleca J.; Jin, Guozhong; Sheng, Zong-Mei; Kaser, Emilee; Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Nolting, Jacqueline M.; Alexander, H. Lloyd, Jr.; Slemons, Richard D.] Ohio State Univ, Dept Vet Prevent Med, Columbus, OH 43210 USA.
RP Taubenberger, JK (reprint author), NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, 33 North Dr,Room 3E19A-2 MSC 3203, Bethesda, MD 20892 USA.
EM taubenbergerj@niaid.nih.gov
RI Nolting, Jacqueline/C-4464-2015
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases; USDA
FX This work was supported by in part by the Intramural Research Program of
the National Institutes of Health, National Institute of Allergy and
Infectious Diseases and in part by the USDA CSREES (NIFA) Coordinated
Agriculture Project (CAP) for the Prevention and Control of Avian
Influenza in the USA, 2005-2007. JMN completed all initial virus
isolations, identifications, and RNA extractions. We thank Seth Schobel
at JCVI for help with submitting the AIV sequences to NCBI. A special
thanks goes to the USDA, APHIS, National Veterinary Service Laboratory,
Ames, Iowa for their excellent support of this investigation. We would
also like to especially thank the conscientious private landowners and
wildlife biologists who provided critical input, access, time and
support for this project thus furthering our understanding of the
natural history of type A influenza viruses in waterfowl.
NR 36
TC 9
Z9 9
U1 0
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD AUG 15
PY 2011
VL 417
IS 1
BP 98
EP 105
DI 10.1016/j.virol.2011.05.004
PG 8
WC Virology
SC Virology
GA 806PO
UT WOS:000293820300012
PM 21658737
ER
PT J
AU Belanger, JM
Raviv, Y
Viard, M
de la Cruz, MJ
Nagashima, K
Blumenthal, R
AF Belanger, Julie M.
Raviv, Yossef
Viard, Mathias
de la Cruz, M. Jason
Nagashima, Kunio
Blumenthal, Robert
TI Effects of UVA irradiation, aryl azides, and reactive oxygen species on
the orthogonal inactivation of the human immunodeficiency virus (HIV-1)
SO VIROLOGY
LA English
DT Article
DE HIV; Detergent; Vaccine; Triton; Hydrophobic; Azide; Reactive oxygen
species (ROS); Viral membrane
ID STRUCTURAL INTEGRITY; IMMUNE-RESPONSES; TYPE-1; PRESERVATION; ENVELOPE;
VACCINES; PROTEIN; IMMUNOGENICITY; VACCINATION; EPITOPES
AB Previously we reported that hydrophobic aryl azides partition into hydrophobic regions of the viral membrane of enveloped viruses and inactivate the virus upon UVA irradiation for 2 min. Prolonged irradiation (15 min) resulted in viral protein aggregation as visualized via Western blot analysis, due to reactive oxygen species (ROS) formation, with preservation of the surface antigenic epitopes. Herein, we demonstrate that these aggregates show detergent resistance and that this property may be useful towards the creation of a novel orthogonal virus inactivation strategy for use in preparing experimental vaccines. When ROS-modified HIV virus preparations were treated with 1% Triton X-100, there was an increase in the percent of viral proteins (gp41, p24) in the viral pellet after ultracentrifugation through sucrose. Transmission electron microscopy (TEM) of these detergent-resistant pellets shows some recognizable virus fragments, and immunoprecipitation studies of the gp41 aggregates suggest the aggregation is covalent in nature, involving short-range interactions. Published by Elsevier Inc.
C1 [Belanger, Julie M.; Blumenthal, Robert] NCI, Ctr Canc Res, Nanobiol Program, Bethesda, MD 20892 USA.
[Raviv, Yossef; Viard, Mathias] NCI Frederick, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
[de la Cruz, M. Jason; Nagashima, Kunio] NCI Frederick, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Blumenthal, R (reprint author), NCI, Ctr Canc Res, Nanobiol Program, Bethesda, MD 20892 USA.
EM blumenthalr@mail.nih.gov
RI Belanger, Julie/A-5734-2009
OI Belanger, Julie/0000-0002-7236-2778
FU Intramural AIDS Targeted Antiviral Program; NIH, National Cancer
Institute, Center for Cancer Research; National Cancer Institute,
National Institutes of Health [HHSN26120080001E]
FX We thank ARRRP for reagents, and Jeff Lifson and the AIDS and Cancer
Virus Program for generously providing purified virus and anti-p17
antibody. We thank Randall Johnson for his assistance with the
statistics. We also thank Julian W. Bess, Jr. for many helpful
discussions and his critical reading of the manuscript. This research
was supported [in part] by federal funds from the Intramural AIDS
Targeted Antiviral Program and the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research. This project
has been funded in whole or in part with federal funds from the National
Cancer Institute, National Institutes of Health, under contract
HHSN26120080001E. 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 26
TC 3
Z9 3
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 0042-6822
J9 VIROLOGY
JI Virology
PD AUG 15
PY 2011
VL 417
IS 1
BP 221
EP 228
DI 10.1016/j.virol.2011.06.007
PG 8
WC Virology
SC Virology
GA 806PO
UT WOS:000293820300026
PM 21726886
ER
PT J
AU Parisi, MA
Spong, CY
Zajicek, A
Guttmacher, AE
AF Parisi, Melissa A.
Spong, Catherine Y.
Zajicek, Anne
Guttmacher, Alan E.
TI We Don't Know What We Don't Study: The Case for Research on Medication
Effects in Pregnancy
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS
LA English
DT Editorial Material
DE medication; exposure; pregnancy; teratogen; research
ID SEROTONIN-REUPTAKE INHIBITORS; BIRTH-DEFECTS; WOMEN; RISK; DRUG;
PHARMACOKINETICS; TRIMESTER
AB This Commentary addresses issues related to exposures to teratogens and makes the case for increased research into the safety of medication usage during pregnancy for mothers and fetuses. Not only are medications commonly used during pregnancy, but evidence points to an increasing prevalence and number of drug exposures experienced by the embryo or fetus, particularly during the critical first trimester of pregnancy. Although the first trimester represents a particularly vulnerable period of organogenesis, exposures during other gestational time periods may also be associated with deleterious outcomes. In addition to the changing (and in many cases unknown) risks to a developing fetus, other challenges to studying medication exposures and their effects during pregnancy include the dramatic changes in physiology that occur in pregnant women and the ethical dilemmas posed by including this vulnerable population in randomized controlled trials of safety and efficacy. However, without adequate knowledge of the pharmacokinetics, pharmacodynamics, efficacy, and safety of medication use in pregnancy, women may be under-dosed to minimize exposure or not treated at all, resulting in inadequate treatment and potential harm to the mother and her baby. The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is undertaking studies on medications and teratogenic exposures during pregnancy, including alcohol, maternal diabetes, oral hypoglycemic agents, and antiviral medications, through several of its research networks. Although this is a start, there is a critical need for further research on medications used during pregnancy, especially their effects on both the mother and her developing child. Published 2011 Wiley-Liss, Inc.(dagger)
C1 [Parisi, Melissa A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intellectual & Dev Disabil Branch, Ctr Dev Biol & Perinatal Med, NIH, Bethesda, MD 20892 USA.
[Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, Bethesda, MD USA.
[Zajicek, Anne] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Obstet & Pediat Pharmacol Branch, Bethesda, MD USA.
RP Parisi, MA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intellectual & Dev Disabil Branch, Ctr Dev Biol & Perinatal Med, NIH, 6100 Execut Blvd,Room 4B09,MSC 7510, Bethesda, MD 20892 USA.
EM parisima@mail.nih.gov
FU Intramural NIH HHS [Z99 HD999999]
NR 23
TC 21
Z9 24
U1 0
U2 11
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1552-4868
J9 AM J MED GENET C
JI Am. J. Med. Genet. C
PD AUG 15
PY 2011
VL 157C
IS 3
SI SI
BP 247
EP 250
DI 10.1002/ajmg.c.30309
PG 4
WC Genetics & Heredity
SC Genetics & Heredity
GA 802VM
UT WOS:000293539100013
PM 21766436
ER
PT J
AU Qu, W
Cheng, LD
Dill, AL
Saavedra, JE
Hong, SY
Keefer, LK
Waalkes, MP
AF Qu, Wei
Cheng, Lida
Dill, Anna L.
Saavedra, Joseph E.
Hong, Sam Y.
Keefer, Larry K.
Waalkes, Michael P.
TI Nitric oxide donor, V-PROLI/NO, provides protection against arsenical
induced toxicity in rat liver cells: Requirement for Cyp1a1
SO CHEMICO-BIOLOGICAL INTERACTIONS
LA English
DT Article
DE V-PROLI/NO; Arsenic; Rat liver cell; Cyp1a1
ID ACUTE PROMYELOCYTIC LEUKEMIA; EPITHELIAL-CELLS; METALLOTHIONEIN;
APOPTOSIS; PRODRUG; CANCER; SENSITIVITY; METABOLISM; ACTIVATION;
MECHANISMS
AB Arsenic is a cancer chemotherapeutic but hepatotoxicity can be a limiting side effect. O(2)-vinyl 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (V-PROLI/NO) is a nitric oxide (NO) donor prodrug and metabolized by liver cytochromes P450 (CYP450) to release NO. The effects of V-PROLI/NO pretreatment on the toxicity of arsenic (as NaAsO(2)) were studied in a rat liver cell line (TRL 1215). The cells acted upon the prodrug to release NO, as assessed by nitrite levels, in a time-dependent fashion to maximal levels of 8-fold above basal levels. Pretreatment with V-PROLI/NO markedly reduced arsenic cytolethality which was directly related to the level of NO produced by V-PROLI/NO treatment. Cyp1a1 expression was directly related to the level of NO production and to reduced arsenic cytotoxicity. V-PROLI/NO pretreatment markedly reduced arsenic-induced apoptosis and suppressed phosphorylation of JNK1/2. V-PROLI/NO pretreatment facilitated additional increases in arsenic-induced metallothionein, a metal-binding protein important in arsenic tolerance. Thus, V-PROLI/NO protects against arsenic toxicity in rat liver cells, reducing cytolethality, apoptosis and dysregulation of MAPKs, through generation of NO formed after metabolism by liver cell enzymes, possibly including Cyp1a1. CYP450 required for NO production from V-PROLI/NO treatment in the rat and human appears to differ as we have previously studied the ability of V-PROLI/NO to prevent arsenic toxicity in human liver cells where it reduced toxicity apparently through a CYP2E1-mediated metabolic mechanism. None-the-less, it appears that both rat and human liver cells act upon V-PROLI/NO via a CYP450-related mechanism to produce NO and subsequently reduce arsenic toxicity. Published by Elsevier Ireland Ltd.
C1 [Qu, Wei; Cheng, Lida; Dill, Anna L.; Waalkes, Michael P.] Natl Inst Environm Hlth Sci, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Qu, Wei; Cheng, Lida; Dill, Anna L.; Waalkes, Michael P.] NCI, Comparat Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA.
[Saavedra, Joseph E.] NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21702 USA.
[Hong, Sam Y.; Keefer, Larry K.] NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA.
RP Waalkes, MP (reprint author), Natl Inst Environm Hlth Sci, Natl Toxicol Program, POB 12233,Mail Drop F0-09,111 Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM waalkes@niehs.nih.gov
RI Keefer, Larry/N-3247-2014
OI Keefer, Larry/0000-0001-7489-9555
FU National Institute of Environmental Health Sciences (NIEHS); National
Institutes of Health (NIH), National Cancer Institute, Center for Cancer
Research; SAIC Frederick, Inc. [HHSN261200800001E]
FX The authors thank Drs. Erik Tokar and Yang Sun for critical review of
this manuscript. This research was supported in part by the National
Toxicology Program, National Institute of Environmental Health Sciences
(NIEHS) and by the Intramural Research Program of the National
Institutes of Health (NIH), National Cancer Institute, Center for Cancer
Research. Additional support came from Contract HHSN261200800001E with
SAIC Frederick, Inc. This article may be the work product of an employee
or a group of employees of the NIEHS, NIH, however, the statements
contained herein do not necessarily represent the statements, opinions
or conclusions of the NIEHS, NIH or the United States Government. The
content of this publication does not necessarily reflect the views or
the 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 40
TC 3
Z9 5
U1 0
U2 6
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0009-2797
J9 CHEM-BIOL INTERACT
JI Chem.-Biol. Interact.
PD AUG 15
PY 2011
VL 193
IS 1
BP 88
EP 96
DI 10.1016/j.cbi.2011.05.005
PG 9
WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology
GA 802EI
UT WOS:000293491700012
PM 21621526
ER
PT J
AU Keembiyehetty, CN
Krzeslak, A
Love, DC
Hanover, JA
AF Keembiyehetty, Chithra N.
Krzeslak, Anna
Love, Dona C.
Hanover, John A.
TI A lipid-droplet-targeted O-GlcNAcase isoform is a key regulator of the
proteasome
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE O-GlcNAcase isoforms; O-GlcNAc cycling; Perilipin-2; Lipid droplets;
Proteasome
ID BETA-N-ACETYLGLUCOSAMINIDASE; CYTOSOLIC PROTEINS; MEXICAN-AMERICANS;
GLYCOSYLATION; INHIBITION; NUCLEAR; PATHWAY; KINASE; GLUCOSAMINIDASE;
PHOSPHORYLATION
AB Protein-O-linked N-Acetyl-beta-D-glucosaminidase (O-GlcNAcase, OGA; also known as hexosaminidase C) participates in a nutrient-sensing, hexosamine signaling pathway by removing O-linked N-acetylglucosamine (O-GlcNAc) from key target proteins. Perturbations in O-GlcNAc signaling have been linked to Alzheimer's disease, diabetes and cancer. Mammalian O-GlcNAcase exists as two major spliced isoforms differing only by the presence (OGA-L) or absence (OGA-S) of a histone-acetyltransferase domain. Here we demonstrate that OGA-S accumulates on the surface of nascent lipid droplets with perilipin-2; both of these proteins are stabilized by proteasome inhibition. We show that selective downregulation of OGA-S results in global proteasome inhibition and the striking accumulation of ubiquitinylated proteins. OGA-S knockdown increased levels of perilipin-2 and perilipin-3 suggesting that O-GlcNAc-dependent regulation of proteasomes might occur on the surface of lipid droplets. By locally activating proteasomes during maturation of the nascent lipid droplet, OGA-S could participate in an O-GlcNAc-dependent feedback loop regulating lipid droplet surface remodeling. Our findings therefore suggest a mechanistic link between hexosamine signaling and lipid droplet assembly and mobilization.
C1 [Keembiyehetty, Chithra N.; Krzeslak, Anna; Love, Dona C.; Hanover, John A.] Natl Inst Diabet & Kidney Dis, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA.
RP Hanover, JA (reprint author), Natl Inst Diabet & Kidney Dis, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA.
EM jah@helix.nih.gov
OI Krzeslak, Anna/0000-0002-4982-7901
FU National Institutes of Health, National Institute for Diabetes and
Digestive and Kidney Diseases
FX We are grateful to the Londos laboratory for providing us with
antibodies to perilipins 1, 2 and 3, and assistance with the lipid
droplet isolation. This research was supported by the Intramural
Research Program of the National Institutes of Health, National
Institute for Diabetes and Digestive and Kidney Diseases. Deposited in
PMC for release after 12 months.
NR 42
TC 29
Z9 30
U1 0
U2 10
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
J9 J CELL SCI
JI J. Cell Sci.
PD AUG 15
PY 2011
VL 124
IS 16
BP 2851
EP 2860
DI 10.1242/jcs.083287
PG 10
WC Cell Biology
SC Cell Biology
GA 800IK
UT WOS:000293352800019
PM 21807949
ER
PT J
AU Chen, X
Oppenheim, JJ
AF Chen, Xin
Oppenheim, Joost J.
TI Comment on "Interplay between TNF and Regulatory T Cells in a TNF-Driven
Murine Model of Arthritis"
SO JOURNAL OF IMMUNOLOGY
LA English
DT Letter
ID EXPRESSION
C1 [Chen, Xin] NCI, Basic Sci Program, Sci Applicat Int Corp Frederick Inc, Mol Immunoregulat Lab, Frederick, MD 21702 USA.
[Oppenheim, Joost J.] NCI, Mol Immunoregulat Lab, Ctr Canc Res, Frederick, MD 21702 USA.
RP Chen, X (reprint author), NCI, Basic Sci Program, Sci Applicat Int Corp Frederick Inc, Mol Immunoregulat Lab, POB B,Bldg 560,Room 31-19, Frederick, MD 21702 USA.
EM chenxin@mail.nih.gov; oppenhej@mail.nih.gov
RI Chen, Xin/I-6601-2015
OI Chen, Xin/0000-0002-2628-4027
NR 9
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD AUG 15
PY 2011
VL 187
IS 4
BP 1527
EP 1527
DI 10.4049/jimmunol.1190029
PG 1
WC Immunology
SC Immunology
GA 800RX
UT WOS:000293384600001
PM 21810616
ER
PT J
AU Fessler, MB
Parks, JS
AF Fessler, Michael B.
Parks, John S.
TI Intracellular Lipid Flux and Membrane Microdomains as Organizing
Principles in Inflammatory Cell Signaling
SO JOURNAL OF IMMUNOLOGY
LA English
DT Review
ID LOW-DENSITY-LIPOPROTEIN; LIGAND-INDEPENDENT ACTIVATION; TOLL-LIKE
RECEPTOR-4; PHOSPHOLIPID OXIDATION-PRODUCTS; FREE-CHOLESTEROL
ACCUMULATION; PLASMA-MEMBRANE; HOST-DEFENSE; ABCA1-DEFICIENT
MACROPHAGES; PERITONEAL-MACROPHAGES; KINASE ACTIVATION
AB Lipid rafts and caveolae play a pivotal role in organization of signaling by TLR4 and several other immune receptors. Beyond the simple cataloguing of signaling events compartmentalized by these membrane microdomains, recent studies have revealed the surprisingly central importance of dynamic remodeling of membrane lipid domains to immune signaling. Simple interventions upon membrane lipid, such as changes in cholesterol loading or crosslinking of raft lipids, are sufficient to induce micrometer-scale reordering of membranes and their protein cargo with consequent signal transduction. In this review, using TLR signaling in the macrophage as a central focus, we discuss emerging evidence that environmental and genetic perturbations of membrane lipid regulate protein signaling, illustrate how homeostatic flow of cholesterol and other lipids through rafts regulates the innate immune response, and highlight recent attempts to harness these insights toward therapeutic development. The Journal of Immunology, 2011, 187: 1529-1535.
C1 [Fessler, Michael B.] Natl Inst Environm Hlth Sci, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA.
[Parks, John S.] Wake Forest Univ, Bowman Gray Sch Med, Dept Pathol & Biochem, Sect Lipid Sci, Winston Salem, NC 27157 USA.
RP Fessler, MB (reprint author), Natl Inst Environm Hlth Sci, Lab Resp Biol, NIH, 111 TW Alexander Dr,POB 12233,MD D2-01, Res Triangle Pk, NC 27709 USA.
EM fesslerm@niehs.nih.gov
FU National Institutes of Health, National Institute of Environmental
Health Sciences [Z01 ES102005]; [HL094525]; [HL049373]
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health, National Institute of Environmental
Health Sciences (Z01 ES102005) and by Grants HL094525 and HL049373 (to
J.S.P.).
NR 92
TC 98
Z9 100
U1 3
U2 15
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD AUG 15
PY 2011
VL 187
IS 4
BP 1529
EP 1535
DI 10.4049/jimmunol.1100253
PG 7
WC Immunology
SC Immunology
GA 800RX
UT WOS:000293384600003
PM 21810617
ER
PT J
AU Lee, JH
Kim, JW
Kim, DK
Kim, HS
Park, HJ
Park, DK
Kim, AR
Kim, B
Beaven, MA
Park, KL
Kim, YM
Choi, WS
AF Lee, Jun Ho
Kim, Jie Wan
Kim, Do Kyun
Kim, Hyuk Soon
Park, Hye Jin
Park, Dong Ki
Kim, A-Ram
Kim, Bokyung
Beaven, Michael A.
Park, Kui Lea
Kim, Young Mi
Choi, Wahn Soo
TI The Src Family Kinase Fgr Is Critical for Activation of Mast Cells and
IgE-Mediated Anaphylaxis in Mice
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID FC-EPSILON-RI; TYROSINE KINASE; ALLERGIC INFLAMMATION; NEGATIVE
REGULATION; IN-VIVO; RECEPTOR; LYN; RESPONSES; SYK; FYN
AB Mast cells are critical for various allergic disorders. Mast cells express Src family kinases, which relay positive and negative regulatory signals by Ag. Lyn, for example, initiates activating signaling events, but it also induces inhibitory signals. Fyn and Hck are reported to be positive regulators, but little is known about the roles of other Src kinases, including Fgr, in mast cells. In this study, we define the role of Fgr. Endogenous Fgr associates with Fc epsilon RI and promotes phosphorylation of Syk, Syk substrates, which include linkers for activation of T cells, SLP76, and Gab2, and downstream targets such as Akt and the MAPKs in Ag-stimulated mast cells. As a consequence, Fgr positively regulates degranulation, production of eicosanoids, and cytokines. Fgr and Fyn appeared to act in concert, as phosphorylation of Syk and degranulation are enhanced by overexpression of Fgr and further augmented by overexpression of Fyn but are suppressed by overexpression of Lyn. Moreover, knockdown of Fgr by small interfering RNAs (siRNAs) further suppressed degranulation in Fyn-deficient bone marrow-derived mast cells. Overexpression of Fyn or Fgr restored phosphorylation of Syk and partially restored degranulation in Fyn-deficient cells. Additionally, knockdown of Fgr by siRNAs inhibited association of Syk with Fc epsilon RI gamma as well as the tyrosine phosphorylation of Fc epsilon RI gamma. Of note, the injection of Fgr siRNAs diminished the protein level of Fgr in mice and simultaneously inhibited IgE-mediated anaphylaxis. In conclusion, Fgr positively regulates mast cell through activation of Syk. These findings help clarify the interplay among Src family kinases and identify Fgr as a potential therapeutic target for allergic diseases. The Journal of Immunology, 2011, 187: 1807-1815.
C1 [Lee, Jun Ho; Kim, Jie Wan; Kim, Do Kyun; Kim, Hyuk Soon; Kim, A-Ram; Kim, Bokyung; Choi, Wahn Soo] Konkuk Univ, Coll Med, Inst Biomed Sci & Technol, Chungju 380701, South Korea.
[Park, Hye Jin; Park, Dong Ki] Konkuk Univ, Dept Biosci & Biotechnol, Seoul 143701, South Korea.
[Beaven, Michael A.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Park, Kui Lea] Korea Food & Drug Adm, Natl Inst Food Drug Safety Evaluat, Ctr Drug Dev Assistance, Cheongwon Gun 363951, South Korea.
[Kim, Young Mi] Duksung Womens Univ, Coll Pharm, Seoul 132714, South Korea.
RP Choi, WS (reprint author), Konkuk Univ, Coll Med, Inst Biomed Sci & Technol, Chungju 380701, South Korea.
EM wahnchoi@kku.ac.kr
FU Ministry for Health, Welfare and Family Affairs, Korea [A084847];
Regional Core Research Program/Chungbuk Biotech-Information Technology
Research-Oriented University Consortium; Ministry of Knowledge Economy
at Konkuk University, Korea; National Heart, Lung, and Blood Institute,
National Institutes of Health
FX This work was supported by a grant from the Korean Health Technology R&D
Project, Ministry for Health, Welfare and Family Affairs, Korea
(A084847), and in part by a grant from the Regional Core Research
Program/Chungbuk Biotech-Information Technology Research-Oriented
University Consortium and the Regional Innovation Center Program of the
Ministry of Knowledge Economy at Konkuk University, Korea. M. A. B. was
supported by the Intramural Program of the National Heart, Lung, and
Blood Institute, National Institutes of Health.
NR 41
TC 23
Z9 27
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 AUG 15
PY 2011
VL 187
IS 4
BP 1807
EP 1815
DI 10.4049/jimmunol.1100296
PG 9
WC Immunology
SC Immunology
GA 800RX
UT WOS:000293384600032
PM 21746961
ER
PT J
AU Bauler, TJ
Chase, JC
Bosio, CM
AF Bauler, Timothy J.
Chase, Jennifer C.
Bosio, Catharine M.
TI IFN-beta Mediates Suppression of IL-12p40 in Human Dendritic Cells
following Infection with Virulent Francisella tularensis
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID INTERFERON-BETA; I INTERFERON; INTRACELLULAR SURVIVAL; PHAGOSOMAL
ESCAPE; AIM2 INFLAMMASOME; MACROPHAGES; TULAREMIA; ACTIVATION;
MATURATION; IMMUNITY
AB Active suppression of inflammation is a strategy used by many viral and bacterial pathogens, including virulent strains of the bacterium Francisella tularensis, to enable colonization and infection in susceptible hosts. In this study, we demonstrated that virulent F. tularensis strain SchuS4 selectively inhibits production of IL-12p40 in primary human cells via induction of IFN-beta. In contrast to the attenuated live vaccine strain, infection of human dendritic cells with virulent SchuS4 failed to induce production of many cytokines associated with inflammation (e.g., TNF-alpha and IL-12p40). Furthermore, SchuS4 actively suppressed secretion of these cytokines. Assessment of changes in the expression of host genes associated with suppression of inflammatory responses revealed that SchuS4, but not live vaccine strain, induced IFN-beta following infection of human dendritic cells. Phagocytosis of SchuS4 and endosomal acidification were required for induction of IFN-beta. Further, using a defined mutant of SchuS4, we demonstrated that the presence of bacteria in the cytosol was required, but not sufficient, for induction of IFN-beta. Surprisingly, unlike previous reports, induction of IFN-beta by F. tularensis was not required for activation of the inflammasome, was not associated with exacerbation of inflammatory responses, and did not control SchuS4 replication when added exogenously. Rather, IFN-beta selectively suppressed the ability of SchuS4-infected dendritic cells to produce IL-12p40. Together, these data demonstrated a novel mechanism by which virulent bacteria, in contrast to attenuated strains, modulate human cells to cause disease. The Journal of Immunology, 2011, 187: 1845-1855.
C1 [Bauler, Timothy J.; Chase, Jennifer C.; Bosio, Catharine M.] NIAID, Immun Pulm Pathogens Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
RP Bosio, CM (reprint author), LICP RML NIAID NIH, 903 S 4th St, Hamilton, MT 59840 USA.
EM bosioc@niaid.nih.gov
RI Bosio, Catharine/D-7456-2015
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases.
NR 56
TC 20
Z9 20
U1 0
U2 2
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD AUG 15
PY 2011
VL 187
IS 4
BP 1845
EP 1855
DI 10.4049/jimmunol.1100377
PG 11
WC Immunology
SC Immunology
GA 800RX
UT WOS:000293384600036
PM 21753150
ER
PT J
AU Mattapallil, MJ
Silver, PB
Mattapallil, JJ
Horai, R
Karabekian, Z
McDowell, JH
Chan, CC
James, EA
Kwok, WW
Sen, HN
Nussenblatt, RB
David, CS
Caspi, RR
AF Mattapallil, Mary J.
Silver, Phyllis B.
Mattapallil, Joseph J.
Horai, Reiko
Karabekian, Zaruhi
McDowell, J. Hugh
Chan, Chi-Chao
James, Eddie A.
Kwok, William W.
Sen, H. Nida
Nussenblatt, Robert B.
David, Chella S.
Caspi, Rachel R.
TI Uveitis-Associated Epitopes of Retinal Antigens Are Pathogenic in the
Humanized Mouse Model of Uveitis and Identify Autoaggressive T Cells
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CLASS-II TETRAMERS; HLA CLASS-II; EXPERIMENTAL AUTOIMMUNE UVEORETINITIS;
COLLAGEN-INDUCED ARTHRITIS; KOYANAGI-HARADA-DISEASE; TRANSGENIC MICE;
S-ANTIGEN; BIRDSHOT RETINOCHOROIDOPATHY; BEHCETS-DISEASE; SYMPATHETIC
OPHTHALMIA
AB Noninfectious uveitis is a leading cause of blindness and thought to involve autoimmune T cell responses to retinal proteins (e. g., retinal arrestin [soluble-Ag (S-Ag)]). There are no known biomarkers for the disease. Susceptibility is associated with HLA, but little is known about susceptible class II alleles or the potentially pathogenic epitopes that they present. Using a humanized HLA-transgenic mouse model of S-Ag-induced autoimmune uveitis, we identified several susceptible and resistant alleles of HLA-DR and -DQ genes and defined pathogenic epitopes of S-Ag presented by the susceptible alleles. The sequences of these epitopes overlap with some previously identified peptides of S-Ag ("M" and "N"), known to elicit memory responses in lymphocytes of uveitis patients. HLA-DR-restricted, S-Ag-specific CD4(+) T cells could be detected in blood and draining lymph nodes of uveitic mice with HLA class II tetramers and transferred the disease to healthy mice. Importantly, tetramer-positive cells were detected in peripheral blood of a uveitis patient. To our knowledge, these findings provide the first tangible evidence that an autoimmune response to retina is causally involved in pathogenesis of human uveitis, demonstrating the feasibility of identifying and isolating retinal Ag-specific T cells from uveitis patients and may facilitate their development as biomarkers for the disease. The Journal of Immunology, 2011, 187: 1977-1985.
C1 [Mattapallil, Mary J.; Silver, Phyllis B.; Horai, Reiko; Karabekian, Zaruhi; Chan, Chi-Chao; Sen, H. Nida; Nussenblatt, Robert B.; Caspi, Rachel R.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Mattapallil, Joseph J.] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, F Edward Hebert Sch Med, Bethesda, MD 20814 USA.
[McDowell, J. Hugh] Univ Florida, Dept Ophthalmol, Gainesville, FL 32610 USA.
[James, Eddie A.; Kwok, William W.] Benaroya Res Inst Virginia Mason, Seattle, WA 98101 USA.
[David, Chella S.] Mayo Clin, Dept Immunol, Rochester, MN 55905 USA.
RP Caspi, RR (reprint author), NEI, Immunol Lab, NIH, Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA.
EM mattapallilm@nei.nih.gov; rcaspi@helix.nih.gov
OI Caspi, Rachel/0000-0002-7140-7671; James, Eddie/0000-0002-7217-5729
FU National Eye Institute, National Institutes of Health; National
Institutes of Allergy and Infectious Diseases; National Institute of
Dental and Craniofacial Research [K22AI07812, R21DE018339]; National
Institutes of Health [EY014864, EY006225]; Research to Prevent Blindness
FX This work was supported by an intramural research grant from the
National Eye Institute, National Institutes of Health. This work was
also supported in part by federal funds from the National Institutes of
Allergy and Infectious Diseases and National Institute of Dental and
Craniofacial Research under Grants K22AI07812 and R21DE018339 (to
J.J.M.). J.H.M. was supported by National Institutes of Health Grants
EY014864 and EY006225 and an unrestricted departmental grant from
Research to Prevent Blindness.
NR 62
TC 16
Z9 16
U1 0
U2 2
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD AUG 15
PY 2011
VL 187
IS 4
BP 1977
EP 1985
DI 10.4049/jimmunol.1101247
PG 9
WC Immunology
SC Immunology
GA 800RX
UT WOS:000293384600050
PM 21765017
ER
PT J
AU Herold, KC
Pescovitz, MD
McGee, P
Krause-Steinrauf, H
Spain, LM
Bourcier, K
Asare, A
Liu, ZG
Lachin, JM
Dosch, HM
AF Herold, Kevan C.
Pescovitz, Mark D.
McGee, Paula
Krause-Steinrauf, Heidi
Spain, Lisa M.
Bourcier, Kasia
Asare, Adam
Liu, Zhugong
Lachin, John M.
Dosch, H. Michael
CA Type 1 Diabet TrialNet Anti-CD20
TI Increased T Cell Proliferative Responses to Islet Antigens Identify
Clinical Responders to Anti-CD20 Monoclonal Antibody (Rituximab) Therapy
in Type 1 Diabetes
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID MULTIPLE-SCLEROSIS; B-LYMPHOCYTES; MICE; DISEASE; PATHOGENESIS;
INITIATION; PHENOTYPE; SUBSETS; INDUCE; ANERGY
AB Type 1 diabetes mellitus is believed to be due to the autoimmune destruction of beta-cells by T lymphocytes, but a single course of rituximab, a monoclonal anti-CD20 B lymphocyte Ab, can attenuate C-peptide loss over the first year of disease. The effects of B cell depletion on disease-associated T cell responses have not been studied. We compare changes in lymphocyte subsets, T cell proliferative responses to disease-associated target Ags, and C-peptide levels of participants who did (responders) or did not (nonresponders) show signs of beta-cell preservation 1 y after rituximab therapy in a placebo-controlled TrialNet trial. Rituximab decreased B lymphocyte levels after four weekly doses of mAb. T cell proliferative responses to diabetes-associated Ags were present at baseline in 75% of anti-CD20- and 82% of placebo-treated subjects and were not different over time. However, in rituximab-treated subjects with significant C-peptide preservation at 6 mo (58%), the proliferative responses to diabetes-associated total (p = 0.032), islet-specific (p = 0.048), and neuronal autoantigens (p = 0.005) increased over the 12-mo observation period. This relationship was not seen in placebo-treated patients. We conclude that in patients with type 1 diabetes mellitus, anti-B cell mAb causes increased proliferative responses to diabetes Ags and attenuated beta-cell loss. The way in which these responses affect the disease course remains unknown. The Journal of Immunology, 2011, 187: 1998-2005.
C1 [Herold, Kevan C.] Yale Univ, Dept Immunobiol, New Haven, CT 06511 USA.
[Pescovitz, Mark D.] Indiana Univ, Dept Surg, Indianapolis, IN 46202 USA.
[McGee, Paula; Krause-Steinrauf, Heidi; Lachin, John M.] George Washington Univ, Biostat Ctr, Washington, DC 20052 USA.
[Spain, Lisa M.] NIDDK, Bethesda, MD 20892 USA.
[Bourcier, Kasia; Asare, Adam; Liu, Zhugong] Immune Tolerance Network, Seattle, WA 98101 USA.
[Dosch, H. Michael] Univ Toronto, Dept Pediat, Toronto, ON M5A 2N4, Canada.
RP Herold, KC (reprint author), Yale Univ, Dept Immunobiol, 300 George St,353, New Haven, CT 06511 USA.
EM kevan.herold@yale.edu
OI Lachin, John/0000-0001-9838-2841
FU Genentech; National Institutes of Health [U01DK085466]; Type 1 Diabetes
TrialNet Anti-CD20 Study Group; National Institutes of Health through
the National Institute of Diabetes and Digestive and Kidney Diseases;
National Institute of Allergy and Infectious Diseases; Eunice Kennedy
Shriver National Institute for Child Health and Human Development;
National Center for Research Resources; Juvenile Diabetes Research
Foundation International; American Diabetes Association
FX M.D.P. has been a speaker and consultant to Roche/Genentech and has
received research support for a clinical trial from Genentech. The other
authors have no financial conflicts of interest.; This work was
supported by National Institutes of Health Grant U01DK085466. The
sponsor of the trial was the Type 1 Diabetes TrialNet Anti-CD20 Study
Group. TrialNet is a clinical trials network funded by the National
Institutes of Health through the National Institute of Diabetes and
Digestive and Kidney Diseases, the National Institute of Allergy and
Infectious Diseases, the Eunice Kennedy Shriver National Institute for
Child Health and Human Development, the National Center for Research
Resources, the Juvenile Diabetes Research Foundation International, and
the American Diabetes Association.
NR 28
TC 30
Z9 32
U1 0
U2 1
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD AUG 15
PY 2011
VL 187
IS 4
BP 1998
EP 2005
DI 10.4049/jimmunol.1100539
PG 8
WC Immunology
SC Immunology
GA 800RX
UT WOS:000293384600052
PM 21775681
ER
PT J
AU Quinn, TC
AF Quinn, Thomas C.
TI Viral Kinetics of Genital Herpes: A Molecular Probe Into Host-Viral
Interactions
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Editorial Material
ID SIMPLEX-VIRUS TYPE-2; ACTIVE ANTIRETROVIRAL THERAPY; RAPIDLY CLEARED
EPISODES; DYNAMICS IN-VIVO; HIV-1 INFECTION; PERINATAL TRANSMISSION;
HSV-2 REACTIVATION; T-CELLS; LOAD; RNA
C1 [Quinn, Thomas C.] NIAID, Immunoregulat Lab, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
RP Quinn, TC (reprint author), Johns Hopkins Univ, 855 N Wolfe St,Rangos 530, Baltimore, MD 21205 USA.
EM tquinn@jhmi.edu
FU Intramural NIH HHS
NR 49
TC 1
Z9 1
U1 1
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD AUG 15
PY 2011
VL 204
IS 4
BP 495
EP 498
DI 10.1093/infdis/jir317
PG 4
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 799RS
UT WOS:000293304400002
PM 21791649
ER
PT J
AU Morens, DM
Holmes, EC
Davis, AS
Taubenberger, JK
AF Morens, David M.
Holmes, Edward C.
Davis, A. Sally
Taubenberger, Jeffery K.
TI Global Rinderpest Eradication: Lessons Learned and Why Humans Should
Celebrate Too
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Editorial Material
ID PHOCINE DISTEMPER VIRUS; MEASLES ERADICATION; GENOME SEQUENCE; DISEASE;
CATTLE; PARAMYXOVIRUSES; MORBILLIVIRUSES; 18TH-CENTURY; TRANSMISSION;
INFECTIONS
C1 [Morens, David M.] NIAID, NIH, Off Director, Bethesda, MD 20892 USA.
[Davis, A. Sally; Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis Sect, Infect Dis Lab, Bethesda, MD 20892 USA.
[Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
RP Morens, DM (reprint author), NIAID, NIH, Off Director, 31 Ctr Dr,Room 7A-03,MSC 2520, Bethesda, MD 20892 USA.
EM dm270q@nih.gov
OI Davis, Anne/0000-0001-5711-3936; Holmes, Edward/0000-0001-9596-3552
FU Intramural NIH HHS
NR 54
TC 22
Z9 24
U1 0
U2 17
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD AUG 15
PY 2011
VL 204
IS 4
BP 502
EP 505
DI 10.1093/infdis/jir327
PG 4
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 799RS
UT WOS:000293304400004
PM 21653230
ER
PT J
AU Wei, Q
Costanzi, S
Liu, QZ
Gao, ZG
Jacobson, KA
AF Wei, Qiang
Costanzi, Stefano
Liu, Qiu-Zhen
Gao, Zhan-Guo
Jacobson, Kenneth A.
TI Activation of the P2Y(1) receptor induces apoptosis and inhibits
proliferation of prostate cancer cells
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE Prostate cancer; P2Y(1) receptor; Apoptosis; Nucleotide; GPCR
ID EXTRACELLULAR ADENOSINE-TRIPHOSPHATE; PROTEIN-COUPLED RECEPTORS;
NUCLEOTIDE RECEPTORS; HUMAN MELANOMAS; IN-VIVO; ASTROCYTES; ATP;
MECHANISMS; EXPRESSION; SURVIVAL
AB G protein-coupled receptors, the largest cell surface receptor family, have emerged as critical players in cell death and survival. High gene expression level of the G(q)-coupled P2Y(1) nucleotide receptor in PC-3 prostate cancer cells was demonstrated using real-time quantitative PCR and confirmed by Western blotting and confocal laser scanning microscopy. A selective P2Y(1) receptor agonist, the ADP analogue MRS2365, concentration-dependently induced intracellular calcium mobilization (EC50 5.28 nM), which was diminished by P2Y(1) receptor-selective antagonist MRS2500. P2Y(1) receptor activation by MRS2365 induced apoptosis in assays of Caspase-3. LDH release, and annexin-V staining. The pro-apoptotic effect of MRS2365 was blocked by MRS2500, P2Y(1) siRNA, and an inhibitor of the MAP kinase pathway PD98059. MRS2365 significantly inhibited the proliferation of PC-3 cells, examined using a MTT assay. Thus, activation of the P2Y(1) receptor induced cell death and inhibited growth of human prostatic carcinoma PC-3 cells. Activation of the P2Y(1) receptor should be a novel and promising therapeutic strategy for prostate cancer. Published by Elsevier Inc.
C1 [Wei, Qiang; Gao, Zhan-Guo; Jacobson, Kenneth A.] NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Wei, Qiang] So Med Univ, Nan Fang Hosp, Guangdong Inst Kidney Dis, Guangzhou 510515, Guangdong, Peoples R China.
[Costanzi, Stefano] NIDDKD, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
[Liu, Qiu-Zhen] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Jacobson, KA (reprint author), NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bldg 8A,Room 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 NIDDK; National Institutes of Health, Bethesda, MD, USA; National
Natural Science Foundation of China [30940072]; Nanfang Hospital,
Southern Medical University, Guangzhou, China
FX Supported by the NIDDK Intramural Research Program, National Institutes
of Health, Bethesda, MD, USA, National Natural Science Foundation of
China (No. 30940072) and Nanfang Hospital, Southern Medical University,
Guangzhou, China. The authors thank Dr. Yafang Hu (Children's National
Medical Center, Washington, DC) for assistance in Western blotting and
confocal microscopy experiments.
NR 33
TC 13
Z9 15
U1 0
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0006-2952
J9 BIOCHEM PHARMACOL
JI Biochem. Pharmacol.
PD AUG 15
PY 2011
VL 82
IS 4
BP 418
EP 425
DI 10.1016/j.bcp.2011.05.013
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 799WF
UT WOS:000293316100011
PM 21632028
ER
PT J
AU Cunningham, K
Uchida, Y
O'Donnell, E
Claudio, E
Li, WL
Soneji, K
Wang, HS
Mukouyama, YS
Siebenlist, U
AF Cunningham, Kirk
Uchida, Yutaka
O'Donnell, Erin
Claudio, Estefania
Li, Wenling
Soneji, Kosha
Wang, Hongshan
Mukouyama, Yoh-suke
Siebenlist, Ulrich
TI Conditional deletion of Ccm2 causes hemorrhage in the adult brain: a
mouse model of human cerebral cavernous malformations
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID KINASE KINASE 3; RECENT INSIGHTS; VASCULAR MALFORMATIONS; SPROUTING
ANGIOGENESIS; ENDOTHELIAL-CELLS; 2-HIT MECHANISM; MUTATIONS; PROTEIN;
GENE; MICE
AB Cerebral cavernous malformations (CCM) are irregularly shaped and enlarged capillaries in the brain that are prone to hemorrhage, resulting in headaches, seizures, strokes and even death in patients. The disease affects up to 0.5% of the population and the inherited form has been linked to mutations in one of three genetic loci, CCM1, CCM2 and CCM3. To understand the pathophysiology underlying the vascular lesions in CCM, it is critical to develop a reproducible mouse genetic model of this disease. Here, we report that limited conditional ablation of Ccm2 in young adult mice induces observable neurological dysfunction and reproducibly results in brain hemorrhages whose appearance is highly reminiscent of the lesions observed in human CCM patients. We first demonstrate that conventional or endothelial-specific deletion of Ccm2 leads to fatal cardiovascular defects during embryogenesis, including insufficient vascular lumen formation as well as defective arteriogenesis and heart malformation. These findings confirm and extend prior studies. We then demonstrate that the inducible deletion of Ccm2 in adult mice recapitulates the CCM-like brain lesions in humans; the lesions display disrupted vascular lumens, enlarged capillary cavities, loss of proper neuro-vascular associations and an inflammatory reaction. The CCM lesions also exhibit damaged neuronal architecture, the likely cause of neurologic defects, such as ataxia and seizure. These mice represent the first CCM2 animal model for CCM and should provide the means to elucidate disease mechanisms and evaluate therapeutic strategies for human CCM.
C1 [Uchida, Yutaka; O'Donnell, Erin; Li, Wenling; Soneji, Kosha; Mukouyama, Yoh-suke] NHLBI, Lab Stem Cell & Neurovasc Biol, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA.
[Cunningham, Kirk; Claudio, Estefania; Wang, Hongshan; Siebenlist, Ulrich] NIAID, Immune Activat Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Mukouyama, YS (reprint author), NHLBI, Lab Stem Cell & Neurovasc Biol, Genet & Dev Biol Ctr, NIH, Bldg 10,Rm 6C103, Bethesda, MD 20892 USA.
EM mukoyamay@mail.nih.gov; ulrich.siebenlist@nih.gov
FU National Institute of Allergy and Infectious Diseases; National Heart,
Lung, and Blood Institute, National Institutes of Health, Bethesda, MD,
USA
FX This work was supported by funding from the Intramural Research Programs
of the National Institute of Allergy and Infectious Diseases and the
National Heart, Lung, and Blood Institute, National Institutes of
Health, Bethesda, MD, USA.
NR 38
TC 16
Z9 17
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD AUG 15
PY 2011
VL 20
IS 16
BP 3198
EP 3206
DI 10.1093/hmg/ddr225
PG 9
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 796CF
UT WOS:000293027100008
PM 21596842
ER
PT J
AU Broeks, A
Schmidt, MK
Sherman, ME
Couch, FJ
Hopper, JL
Dite, GS
Apicella, C
Smith, LD
Hammet, F
Southey, MC
Van 't Veer, LJ
de Groot, R
Smit, VTHBM
Fasching, PA
Beckmann, MW
Jud, S
Ekici, AB
Hartmann, A
Hein, A
Schulz-Wendtland, R
Burwinkel, B
Marme, F
Schneeweiss, A
Sinn, HP
Sohn, C
Tchatchou, S
Bojesen, SE
Nordestgaard, BG
Flyger, H
Orsted, DD
Kaur-Knudsen, D
Milne, RL
Perez, JIA
Zamora, P
Rodriguez, PM
Benitez, J
Brauch, H
Justenhoven, C
Ko, YD
Hamann, U
Fischer, HP
Bruning, T
Pesch, B
Chang-Claude, J
Wang-Gohrke, S
Bremer, M
Karstens, JH
Hillemanns, P
Dork, T
Nevanlinna, HA
Heikkinen, T
Heikkila, P
Blomqvist, C
Aittomaki, K
Aaltonen, K
Lindblom, A
Margolin, S
Mannermaa, A
Kosma, VM
Kauppinen, JM
Kataja, V
Auvinen, P
Eskelinen, M
Soini, Y
Chenevix-Trench, G
Spurdle, AB
Beesley, J
Chen, XQ
Holland, H
Lambrechts, D
Claes, B
Vandorpe, T
Neven, P
Wildiers, H
Flesch-Janys, D
Hein, R
Loning, T
Kosel, M
Fredericksen, ZS
Wang, XS
Giles, GG
Baglietto, L
Severi, G
McLean, C
Haiman, CA
Henderson, BE
Le Marchand, L
Kolonel, LN
Alnaes, GG
Kristensen, V
Borresen-Dale, AL
Hunter, DJ
Hankinson, SE
Andrulis, IL
Mulligan, AM
O'Malley, FP
Devilee, P
Huijts, PEA
Tollenaar, RAEM
Van Asperen, CJ
Seynaeve, CS
Chanock, SJ
Lissowska, J
Brinton, L
Peplonska, B
Figueroa, J
Yang, XHR
Hooning, MJ
Hollestelle, A
Oldenburg, RA
Jager, A
Kriege, M
Ozturk, B
van Leenders, GJLH
Hall, P
Czene, K
Humphreys, K
Liu, JJ
Cox, A
Connley, D
Cramp, HE
Cross, SS
Balasubramanian, SP
Reed, MWR
Dunning, AM
Easton, DF
Humphreys, MK
Caldas, C
Blows, F
Driver, K
Provenzano, E
Lubinski, J
Jakubowska, A
Huzarski, T
Byrski, T
Cybulski, C
Gorski, B
Gronwald, J
Brennan, P
Sangrajrang, S
Gaborieau, V
Shen, CY
Hsiung, CN
Yu, JC
Chen, ST
Hsu, GC
Hou, MF
Huang, CS
Anton-Culver, H
Ziogas, A
Pharoah, PDP
Garcia-Closas, M
AF Broeks, Annegien
Schmidt, Marjanka K.
Sherman, Mark E.
Couch, Fergus J.
Hopper, John L.
Dite, Gillian S.
Apicella, Carmel
Smith, Letitia D.
Hammet, Fleur
Southey, Melissa C.
Van 't Veer, Laura J.
de Groot, Renate
Smit, Vincent T. H. B. M.
Fasching, Peter A.
Beckmann, Matthias W.
Jud, Sebastian
Ekici, Arif B.
Hartmann, Arndt
Hein, Alexander
Schulz-Wendtland, Ruediger
Burwinkel, Barbara
Marme, Frederik
Schneeweiss, Andreas
Sinn, Hans-Peter
Sohn, Christof
Tchatchou, Sandrine
Bojesen, Stig E.
Nordestgaard, Borge G.
Flyger, Henrik
Orsted, David D.
Kaur-Knudsen, Diljit
Milne, Roger L.
Perez, Jose I. Arias
Zamora, Pilar
Menendez Rodriguez, Primitiva
Benitez, Javier
Brauch, Hiltrud
Justenhoven, Christina
Ko, Yon-Dschun
Hamann, Ute
Fischer, Hans-Peter
Bruening, Thomas
Pesch, Beate
Chang-Claude, Jenny
Wang-Gohrke, Shan
Bremer, Michael
Karstens, Johann H.
Hillemanns, Peter
Doerk, Thilo
Nevanlinna, Heli A.
Heikkinen, Tuomas
Heikkila, Paeivi
Blomqvist, Carl
Aittomaki, Kristiina
Aaltonen, Kirsimari
Lindblom, Annika
Margolin, Sara
Mannermaa, Arto
Kosma, Veli-Matti
Kauppinen, Jaana M.
Kataja, Vesa
Auvinen, Paeivi
Eskelinen, Matti
Soini, Ylermi
Chenevix-Trench, Georgia
Spurdle, Amanda B.
Beesley, Jonathan
Chen, Xiaoqing
Holland, Helene
Lambrechts, Diether
Claes, Bart
Vandorpe, Thijs
Neven, Patrick
Wildiers, Hans
Flesch-Janys, Dieter
Hein, Rebecca
Loening, Thomas
Kosel, Matthew
Fredericksen, Zachary S.
Wang, Xianshu
Giles, Graham G.
Baglietto, Laura
Severi, Gianluca
McLean, Catriona
Haiman, Christopher A.
Henderson, Brian E.
Le Marchand, Loic
Kolonel, Laurence N.
Alnaes, Grethe Grenaker
Kristensen, Vessela
Borresen-Dale, Anne-Lise
Hunter, David J.
Hankinson, Susan E.
Andrulis, Irene L.
Mulligan, Anna Marie
O'Malley, Frances P.
Devilee, Peter
Huijts, Petra E. A.
Tollenaar, Rob A. E. M.
Van Asperen, Christi J.
Seynaeve, Caroline S.
Chanock, Stephen J.
Lissowska, Jolanta
Brinton, Louise
Peplonska, Beata
Figueroa, Jonine
Yang, Xiaohong R.
Hooning, Maartje J.
Hollestelle, Antoinette
Oldenburg, Rogier A.
Jager, Agnes
Kriege, Mieke
Ozturk, Bahar
van Leenders, Geert J. L. H.
Hall, Per
Czene, Kamila
Humphreys, Keith
Liu, Jianjun
Cox, Angela
Connley, Daniel
Cramp, Helen E.
Cross, Simon S.
Balasubramanian, Sabapathy P.
Reed, Malcolm W. R.
Dunning, Alison M.
Easton, Douglas F.
Humphreys, Manjeet K.
Caldas, Carlos
Blows, Fiona
Driver, Kristy
Provenzano, Elena
Lubinski, Jan
Jakubowska, Anna
Huzarski, Tomasz
Byrski, Tomasz
Cybulski, Cezary
Gorski, Bohdan
Gronwald, Jacek
Brennan, Paul
Sangrajrang, Suleeporn
Gaborieau, Valerie
Shen, Chen-Yang
Hsiung, Chia-Ni
Yu, Jyh-Cherng
Chen, Shou-Tung
Hsu, Giu-Cheng
Hou, Ming-Feng
Huang, Chiun-Sheng
Anton-Culver, Hoda
Ziogas, Argyrios
Pharoah, Paul D. P.
Garcia-Closas, Montserrat
CA Genica Network
KConFab
AOCS
TI Low penetrance breast cancer susceptibility loci are associated with
specific breast tumor subtypes: findings from the Breast Cancer
Association Consortium
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID BRCA2 MUTATION CARRIERS; GENOME-WIDE ASSOCIATION; ESTROGEN-RECEPTOR;
COMMON VARIANTS; CONFER SUSCEPTIBILITY; RISK PREDICTION; EXPRESSION;
PATTERNS; ALLELES; POPULATION
AB Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtypes were defined by five markers (ER, PR, HER2, CK5/6, EGFR) and other pathological and clinical features. Analyses included up to 30 040 invasive breast cancer cases and 53 692 controls from 31 studies within the Breast Cancer Association Consortium. We confirmed previous reports of stronger associations with ER+ than ER- tumors for six of the eight loci identified in GWAS: rs2981582 (10q26) (P-heterogeneity = 6.1 x 10(-18)), rs3803662 (16q12) (P = 3.7 x 10(-5)), rs13281615 (8q24) (P = 0.002), rs13387042 (2q35) (P = 0.006), rs4973768 (3p24) (P = 0.003) and rs6504950 (17q23) (P = 0.002). The two candidate loci, CASP8 (rs1045485, rs17468277) and TGFB1 (rs1982073), were most strongly related with the risk of PR negative tumors (P = 5.1 x 10(-6) and P = 4.1 x 10(-4), respectively), as previously suggested. Four of the eight loci identified in GWAS were associated with triple negative tumors (P <= 0.016): rs3803662 (16q12), rs889312 (5q11), rs3817198 (11p15) and rs13387042 (2q35); however, only two of them (16q12 and 2q35) were associated with tumors with the core basal phenotype (P <= 0.002). These analyses are consistent with different biological origins of breast cancers, and indicate that tumor stratification might help in the identification and characterization of novel risk factors for breast cancer subtypes. This may eventually result in further improvements in prevention, early detection and treatment.
C1 [Broeks, Annegien; Schmidt, Marjanka K.; Van 't Veer, Laura J.] Netherlands Canc Inst, Dept Expt Therapy, NL-1066 CX Amsterdam, Netherlands.
[Schmidt, Marjanka K.] Netherlands Canc Inst, Dept Epidemiol, NL-1066 CX Amsterdam, Netherlands.
[Van 't Veer, Laura J.; de Groot, Renate] Netherlands Canc Inst, Dept Mol Pathol, NL-1066 CX Amsterdam, Netherlands.
[Sherman, Mark E.; Figueroa, Jonine; Yang, Xiaohong R.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Couch, Fergus J.; Kosel, Matthew; Fredericksen, Zachary S.; Wang, Xianshu] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Couch, Fergus J.; Kosel, Matthew; Fredericksen, Zachary S.; Wang, Xianshu] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Hopper, John L.; Dite, Gillian S.; Apicella, Carmel] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic 3010, Australia.
[Smith, Letitia D.; Hammet, Fleur; Southey, Melissa C.] Univ Melbourne, Genet Epidemiol Lab, Dept Pathol, Melbourne, Vic 3010, Australia.
[Smit, Vincent T. H. B. M.] Leiden Univ, Dept Pathol, Med Ctr, Leiden, Netherlands.
[Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA.
[Beckmann, Matthias W.; Jud, Sebastian; Hein, Alexander] Univ Hosp Erlangen, Univ Breast Ctr, Dept Gynecol & Obstet, Erlangen, Germany.
[Hartmann, Arndt] Univ Hosp Erlangen, Univ Breast Ctr, Inst Pathol, Erlangen, Germany.
[Schulz-Wendtland, Ruediger] Univ Hosp Erlangen, Univ Breast Ctr, Inst Radiol, Erlangen, Germany.
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[Brauch, Hiltrud; Justenhoven, Christina] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-7000 Stuttgart, Germany.
[Brauch, Hiltrud; Justenhoven, Christina] Univ Tubingen, Tubingen, Germany.
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Univ Bonn, Fac Med, Inst Pathol, D-5300 Bonn, Germany.
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[Hamann, Ute] Deutsch Krebsforschungszentrum DKFZ, Heidelberg, Germany.
[Fischer, Hans-Peter] Univ Bonn, Fac Med, Inst Pathol, D-5300 Bonn, Germany.
[Bruening, Thomas; Pesch, Beate] Inst Prevent & Occupat Med German Social Accid In, Bochum, Germany.
[Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynecol, Ulm, Germany.
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Univ Helsinki, Cent Hosp, Dept Oncol, FIN-00290 Helsinki, Finland.
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[Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, Hamburg, Germany.
[Loening, Thomas] Albertinen Pathol Dept, Hamburg, Germany.
Univ Heidelberg Hosp, Dept Pathol, Heidelberg, Germany.
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[Haiman, Christopher A.; Henderson, Brian E.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA.
[Haiman, Christopher A.; Henderson, Brian E.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90089 USA.
[Le Marchand, Loic; Kolonel, Laurence N.] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA.
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[Devilee, Peter] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands.
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RP Broeks, A (reprint author), Netherlands Canc Inst, Div Expt Therapy C2, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands.
EM a.broeks@nki.nl
RI Caldas, Carlos/A-7543-2008; Peplonska, Beata/F-6004-2010; Smith, Letitia
/J-9035-2014; Hein, Alexander/F-6999-2010; BYRSKI, Tomasz/I-2844-2014;
Jakubowska, Anna/O-8050-2014; Garcia-Closas, Montserrat /F-3871-2015;
Brinton, Louise/G-7486-2015; Shen, CY/F-6271-2010; Verdrengh,
Evelien/H-4571-2012; Ekici, Arif/C-3971-2013; Andrulis,
Irene/E-7267-2013; Dork, Thilo/J-8620-2012; Hartikainen,
Jaana/E-6256-2015; Bowtell, David/H-1007-2016; Bruning,
Thomas/G-8120-2015; Gronwald, Jacek/A-4576-2017; Spurdle,
Amanda/A-4978-2011;
OI Hein, Alexander/0000-0003-2601-3398; Garcia-Closas, Montserrat
/0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Bowtell,
David/0000-0001-9089-7525; Bruning, Thomas/0000-0001-9560-5464;
Gronwald, Jacek/0000-0002-3643-2871; Dite, Gillian/0000-0002-2448-2548;
Czene, Kamila/0000-0002-3233-5695; Spurdle, Amanda/0000-0003-1337-7897;
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]; CR-UK [C1287/A10118,
C1287/A7497, C1287/A12014, C8197/A10865]; European Union [BM0606,
LSHC-CT-2003-503297]; National Health and Medical Research Council of
Australia [199600]; New South Wales Cancer Council; Victorian Health
Promotion Foundation (Australia); National Cancer Institute, National
Institutes of Health [RFA-CA-06-503, CA-06-503, CA-58860]; Dutch Cancer
Society [NKI 2001-2423, 2007-3839, DDHK 2004-3124]; Dutch National
Genomics Initiative; University of Erlangen; Dr Mildred Scheel Stiftung
of the Deutsche Krebshilfe e.V; Dietmar-Hopp Foundation; Helmholtz
Society; Chief Physician Johan Boserup and Lise Boserup Fund; Danish
Medical Research Council; Copenhagen University Hospital, Herlev
Hospital; Red Tematica de Investigacion Cooperativa en Cancer;
Asociacion Espanola Contra Cancer; Fondo de Investigacion Sanitario
[PI081120, PI081583]; Federal Ministry of Education and Research (BMBF)
Germany [01KW9975/5, 01KW9976/8, 01KW9977/0, 01KW0114]; Deutsche
Krebshilfe e.V [70492, 70-2892-BR I]; Hannover Medical School; Helsinki
University Central Hospital; Academy of Finland [110663]; Finnish Cancer
Society; Sigrid Juselius Foundation; Swedish Cancer Society; Gustav V
Jubilee Foundation; Bert von Kantzow Foundation; Kuopio University;
University of Kuopio; EVO research funding of Vaasa Hospital District;
National Breast Cancer Foundation; National Health and Medical Research
Council (NHMRC) [145684, 288704, 454508, 209057, 251533, 396414, 504711,
504715]; 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; US Army
Medical Research and Material Command [DAMD17-01-1-0729]; Cancer Council
Tasmania and Cancer Foundation of Western Australia; Stichting tegen
Kanker [232-2008]; Hamburg Cancer Society; German Cancer Research
Center; German Federal Ministry of Education and Research [01KH0402];
National Institutes of Health [R01 CA122340, R01-CA63464, R37-CA54281];
NCI Specialized Program of Research Excellence (SPORE) in breast cancer
[P50 CA116201]; Cancer Council Victoria; Norwegian Research council
[155218/V40, 175240/S10, 181600/V11]; Swizz Bridge Award; Cancer Care
Ontario [U01 CA69467]; Northern California Cancer Center [U01 CA69417];
University of Melbourne [U01 CA69638]; National Cancer Institute,
Department of Health and Human Services, USA; Agency for Science,
Technology and Research of Singapore (A*STAR); US National Institute of
Health (NIH); Susan G. Komen Breast Cancer Foundation; Breast Cancer
Campaign; Yorkshire Cancer Research; Cancer Research UK [C1287/A10118,
C490/A1102, C8197/A10123, C490/A10119, C490/A11020]; NIHR Cambridge
Biomedical Research Centre; Cambridge Experimental Cancer Medicine
Centre; National Cancer Institute Thailand; Institute of Biomedical
Sciences, Academia Sinica, National Sciences Counciland Taiwan Biobank;
Lon V Smith Foundation [LVS-39420]; [PBZ_KBN_122/P05/2004]
FX This work was supported by funding from the European Community's Seventh
Framework Programme under grant agreement no. 223175
(HEALTH-F2-2009-223175). The BCAC is funded by CR-UK (C1287/A10118,
C1287/A7497, C1287/A12014). Meetings of the BCAC have been funded by the
European Union COST program (BM0606). D.F.E. is a Principal Research
Fellow of CR-UK. The ABCFS study was supported by the National Health
and Medical Research Council of Australia, the New South Wales Cancer
Council, the Victorian Health Promotion Foundation (Australia) and the
National Cancer Institute, National Institutes of Health under
RFA-CA-06-503 and through cooperative agreements with members of the
Breast Cancer Family Registry (CFR) and P.I.s. The ABCS study was
supported by the Dutch Cancer Society (grants NKI 2001-2423; 2007-3839)
and the Dutch National Genomics Initiative. The BBCC study was partly
funded by a Grand of ELAN Funding of the University of Erlangen. P.A.F.
is partly funded by Dr Mildred Scheel Stiftung of the Deutsche
Krebshilfe e.V. The BSUCH study was supported by the Dietmar-Hopp
Foundation and the Helmholtz Society. The CGPS study was supported by
the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish
Medical Research Council and Copenhagen University Hospital, Herlev
Hospital. The CNIO-BCS study was supported by the Red Tematica de
Investigacion Cooperativa en Cancer and grants from the Asociacion
Espanola Contra Cancer and the Fondo de Investigacion Sanitario
(PI081120 to JB and PI081583 to RLM). The GENICA study was supported by
the German Human Genome Project and funded by the Federal Ministry of
Education and Research (BMBF) Germany (grants 01KW9975/5, 01KW9976/8,
01KW9977/0 and 01KW0114). The Robert Bosch Foundation of Medical
Research, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ),
Heidelberg, Institute for Prevention and Occupational Medicine of the
German Social Accident Insurance (IPA), Bochum as well as the Department
of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter
Krankenhaus, Bonn, Germany. The GESBC study was supported by the
Deutsche Krebshilfe e.V. (70492) and GESBC genotyping in part by the
state of Baden-Wurttemberg through the Medical Faculty of the University
of Ulm (P.685). The HABCS study was supported by an intramural grant
from Hannover Medical School. The HEBCS study has been financially
supported by the Helsinki University Central Hospital Research Fund,
Academy of Finland (110663), the Finnish Cancer Society and the Sigrid
Juselius Foundation. The KARBAC study was supported by The Swedish
Cancer Society, The Gustav V Jubilee Foundation And The Bert von Kantzow
Foundation. The KBCP was supported by the Kuopio University Central EVO
Research Fund, Academy of Finland, the Finnish Cancer Society, the
University of Kuopio and EVO research funding of Vaasa Hospital
District. The kConFab and its Clinical Follow-Up study were funded by
grants from the National Breast Cancer Foundation, the National Health
and Medical Research Council (NHMRC) and by the Queensland Cancer Fund,
the Cancer Councils of New South Wales, Victoria, Tasmania and South
Australia and the Cancer Foundation of Western Australia, as well as by
NHMRC (grants 145684, 288704 and 454508). The AOCS study was supported
by the US Army Medical Research and Material Command (DAMD17-01-1-0729),
the Cancer Council Tasmania and Cancer Foundation of Western Australia
and The National Health and Medical Research Council of Australia
(199600). Amanda B.; Spurdle is supported by an NHMRC Senior Research
Fellowship, and Georgia Chenevx-Trench by an NHMRC Senior Principal
Research Fellowship The LMBC stduy was supported by European Union
Framework Programme 6 (Project LSHC-CT-2003-503297) and by the
'Stichting tegen Kanker' (232-2008). The MARIE study was supported by
the Deutsche Krebshilfe e.V., (grant70-2892-BR I), the Hamburg Cancer
Society, the German Cancer Research Center and the German Federal
Ministry of Education and Research (01KH0402). The MCBCS was supported
by National Institutes of Health (grant R01 CA122340), and an NCI
Specialized Program of Research Excellence (SPORE) in breast cancer (P50
CA116201). The MCCS study was supported by Cancer Council Victoria and
by NHMRC (grants 209057, 251533, 396414,504711, 504715). The MEC study
was supported by National Institutes of Health (grants R01-CA63464,
R37-CA54281). The NBCS study was supported by grants from the Norwegian
Research council, (155218/V40, 175240/S10) to ALBD, FUGE-NFR
(181600/V11) to VNK and a Swizz Bridge Award to ALBD. The OFBCR was
supported by the National Cancer Institute, National Institutes of
Health under (grant 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), Northern
California Cancer Center (U01 CA69417), and University of Melbourne (U01
CA69638) and by Cancer Care Ontario. 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 the
mention of trade names, commercial products or organizations imply
endorsement by the US Government or the BCFR. The ORIGO study was
supported by the Dutch Cancer Society. The PBCS was supported by
Intramural Research Funds of the National Cancer Institute, Department
of Health and Human Services, USA. The RBCS study was supported by the
Dutch Cancer Society (grant DDHK 2004-3124). The SASBAC study was
supported by funding from the Agency for Science, Technology and
Research of Singapore (A*STAR), the US National Institute of Health
(NIH) and the Susan G. Komen Breast Cancer Foundation. The SBCS study
was funded by the Breast Cancer Campaign (grant 2004Nov 49) and
Yorkshire Cancer Research core funding. SEARCH study was supported by
Cancer Research UK grants (C490/A1102, C8197/A10123, C490/A10119,
C490/A11020, C1287/A10118) and AMD was funded by CR-UK grant
(C8197/A10865). The pathology work in Cambridge was supported by the
NIHR Cambridge Biomedical Research Centre and by the Cambridge
Experimental Cancer Medicine Centre. The SZBCS was supported by Grant
(PBZ_KBN_122/P05/2004). The TBCS was funded by The National Cancer
Institute Thailand. The TWBCS study was supported by the Institute of
Biomedical Sciences, Academia Sinica, National Sciences Counciland
Taiwan Biobank. The UCIBCS study was supported by the National
Institutes of Health, National Cancer Institute (grants CA-58860) and
the Lon V Smith Foundation (grant LVS-39420).
NR 39
TC 100
Z9 100
U1 1
U2 15
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD AUG 15
PY 2011
VL 20
IS 16
BP 3289
EP 3303
DI 10.1093/hmg/ddr228
PG 15
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 796CF
UT WOS:000293027100016
PM 21596841
ER
PT J
AU Antoniou, AC
Kartsonaki, C
Sinilnikova, OM
Soucy, P
McGuffog, L
Healey, S
Lee, A
Peterlongo, P
Manoukian, S
Peissel, B
Zaffaroni, D
Cattaneo, E
Barile, M
Pensotti, V
Pasini, B
Dolcetti, R
Giannini, G
Putignano, AL
Varesco, L
Radice, P
Mai, PL
Greene, MH
Andrulis, IL
Glendon, G
Ozcelik, H
Thomassen, M
Gerdes, AM
Kruse, TA
Jensen, UB
Cruger, DG
Caligo, MA
Laitman, Y
Milgrom, R
Kaufman, B
Paluch-Shimon, S
Friedman, E
Loman, N
Harbst, K
Lindblom, A
Arver, B
Ehrencrona, H
Melin, B
Nathanson, KL
Domchek, SM
Rebbeck, T
Jakubowska, A
Lubinski, J
Gronwald, J
Huzarski, T
Byrski, T
Cybulski, C
Gorski, B
Osorio, A
Cajal, TRY
Fostira, F
Andres, R
Benitez, J
Hamann, U
Hogervorst, FB
Rookus, MA
Hooning, MJ
Nelen, MR
van der Luijt, RB
van Os, TAM
van Asperen, CJ
Devilee, P
Meijers-Heijboer, HEJ
Garcia, EBG
Peock, S
Cook, M
Frost, D
Platte, R
Leyland, J
Evans, DG
Lalloo, F
Eeles, R
Izatt, L
Adlard, J
Davidson, R
Eccles, D
Ong, KR
Cook, J
Douglas, F
Paterson, J
Kennedy, MJ
Miedzybrodzka, Z
Godwin, A
Stoppa-Lyonnet, D
Buecher, B
Belotti, M
Tirapo, C
Mazoyer, S
Barjhoux, L
Lasset, C
Leroux, D
Faivre, L
Bronner, M
Prieur, F
Nogues, C
Rouleau, E
Pujol, P
Coupier, I
Frenay, M
Hopper, JL
Daly, MB
Terry, MB
John, EM
Buys, SS
Yassin, Y
Miron, A
Goldgar, D
Singer, CF
Tea, MK
Pfeiler, G
Dressler, AC
Hansen, TV
Jonson, L
Ejlertsen, B
Barkardottir, RB
Kirchhoff, T
Offit, K
Piedmonte, M
Rodriguez, G
Small, L
Boggess, J
Blank, S
Basil, J
Azodi, M
Toland, AE
Montagna, M
Tognazzo, S
Agata, S
Imyanitov, E
Janavicius, R
Lazaro, C
Blanco, I
Pharoah, PDP
Sucheston, L
Karlan, BY
Walsh, CS
Olah, E
Bozsik, A
Teo, SH
Seldon, JL
Beattie, MS
van Rensburg, EJ
Sluiter, MD
Diez, O
Schmutzler, RK
Wappenschmidt, B
Engel, C
Meindl, A
Ruehl, I
Varon-Mateeva, R
Kast, K
Deissler, H
Niederacher, D
Arnold, N
Gadzicki, D
Schonbuchner, I
Caldes, T
de la Hoya, M
Nevanlinna, H
Aittomaki, K
Dumont, M
Chiquette, J
Tischkowitz, M
Chen, XQ
Beesley, J
Spurdle, AB
Neuhausen, SL
Ding, YC
Fredericksen, Z
Wang, X
Pankratz, VS
Couch, F
Simard, J
Easton, DF
Chenevix-Trench, G
AF Antoniou, Antonis C.
Kartsonaki, Christiana
Sinilnikova, Olga M.
Soucy, Penny
McGuffog, Lesley
Healey, Sue
Lee, Andrew
Peterlongo, Paolo
Manoukian, Siranoush
Peissel, Bernard
Zaffaroni, Daniela
Cattaneo, Elisa
Barile, Monica
Pensotti, Valeria
Pasini, Barbara
Dolcetti, Riccardo
Giannini, Giuseppe
Putignano, Anna Laura
Varesco, Liliana
Radice, Paolo
Mai, Phuong L.
Greene, Mark H.
Andrulis, Irene L.
Glendon, Gord
Ozcelik, Hilmi
Thomassen, Mads
Gerdes, Anne-Marie
Kruse, Torben A.
Jensen, Uffe Birk
Crueger, Dorthe G.
Caligo, Maria A.
Laitman, Yael
Milgrom, Roni
Kaufman, Bella
Paluch-Shimon, Shani
Friedman, Eitan
Loman, Niklas
Harbst, Katja
Lindblom, Annika
Arver, Brita
Ehrencrona, Hans
Melin, Beatrice
Nathanson, Katherine L.
Domchek, Susan M.
Rebbeck, Timothy
Jakubowska, Ania
Lubinski, Jan
Gronwald, Jacek
Huzarski, Tomasz
Byrski, Tomasz
Cybulski, Cezary
Gorski, Bohdan
Osorio, Ana
Ramon y Cajal, Teresa
Fostira, Florentia
Andres, Raquel
Benitez, Javier
Hamann, Ute
Hogervorst, Frans B.
Rookus, Matti A.
Hooning, Maartje J.
Nelen, Marcel R.
van der Luijt, Rob B.
van Os, Theo A. M.
van Asperen, Christi J.
Devilee, Peter
Meijers-Heijboer, Hanne E. J.
Garcia, Encarna B. Gomez
Peock, Susan
Cook, Margaret
Frost, Debra
Platte, Radka
Leyland, Jean
Evans, D. Gareth
Lalloo, Fiona
Eeles, Ros
Izatt, Louise
Adlard, Julian
Davidson, Rosemarie
Eccles, Diana
Ong, Kai-ren
Cook, Jackie
Douglas, Fiona
Paterson, Joan
Kennedy, M. John
Miedzybrodzka, Zosia
Godwin, Andrew
Stoppa-Lyonnet, Dominique
Buecher, Bruno
Belotti, Muriel
Tirapo, Carole
Mazoyer, Sylvie
Barjhoux, Laure
Lasset, Christine
Leroux, Dominique
Faivre, Laurence
Bronner, Myriam
Prieur, Fabienne
Nogues, Catherine
Rouleau, Etienne
Pujol, Pascal
Coupier, Isabelle
Frenay, Marc
Hopper, John L.
Daly, Mary B.
Terry, Mary B.
John, Esther M.
Buys, Saundra S.
Yassin, Yosuf
Miron, Alexander
Goldgar, David
Singer, Christian F.
Tea, Muy-Kheng
Pfeiler, Georg
Dressler, Anne Catharina
Hansen, Thomas v. O.
Jonson, Lars
Ejlertsen, Bent
Barkardottir, Rosa Bjork
Kirchhoff, Tomas
Offit, Kenneth
Piedmonte, Marion
Rodriguez, Gustavo
Small, Laurie
Boggess, John
Blank, Stephanie
Basil, Jack
Azodi, Masoud
Toland, Amanda Ewart
Montagna, Marco
Tognazzo, Silvia
Agata, Simona
Imyanitov, Evgeny
Janavicius, Ramunas
Lazaro, Conxi
Blanco, Ignacio
Pharoah, Paul D. P.
Sucheston, Lara
Karlan, Beth Y.
Walsh, Christine S.
Olah, Edith
Bozsik, Aniko
Teo, Soo-Hwang
Seldon, Joyce L.
Beattie, Mary S.
van Rensburg, Elizabeth J.
Sluiter, Michelle D.
Diez, Orland
Schmutzler, Rita K.
Wappenschmidt, Barbara
Engel, Christoph
Meindl, Alfons
Ruehl, Ina
Varon-Mateeva, Raymonda
Kast, Karin
Deissler, Helmut
Niederacher, Dieter
Arnold, Norbert
Gadzicki, Dorothea
Schoenbuchner, Ines
Caldes, Trinidad
de la Hoya, Miguel
Nevanlinna, Heli
Aittomaki, Kristiina
Dumont, Martine
Chiquette, Jocelyne
Tischkowitz, Marc
Chen, Xiaoqing
Beesley, Jonathan
Spurdle, Amanda B.
Neuhausen, Susan L.
Ding, Yuan Chun
Fredericksen, Zachary
Wang, Xianshu
Pankratz, Vernon S.
Couch, Fergus
Simard, Jacques
Easton, Douglas F.
Chenevix-Trench, Georgia
CA SWE-BRCA
HEBON
EMBRACE
CEMO Study Collaborators
Breast Canc Family Registry
kConFab Investigators
CIMBA
TI Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer
risk for BRCA1 and BRCA2 mutation carriers
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; ESTROGEN-RECEPTOR; CONFER SUSCEPTIBILITY;
GENETIC MODIFIERS; VARIANTS; LOCUS; POPULATION; 2Q35
AB Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [ hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 x 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 x 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.
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[Pharoah, Paul D. P.] Univ Cambridge, Dept Oncol, Cambridge CB1 8RN, England.
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Univ Laval, Quebec City, PQ, Canada.
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Univ Milan, Dept Med Surg & Dent, Milan, Italy.
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[Eccles, Diana] Princess Anne Hosp, Wessex Clin Genet Serv, Southampton, Hants, England.
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[Stoppa-Lyonnet, Dominique] Univ Paris 05, Fac Med, Paris, France.
[Lasset, Christine] Univ Lyon 1, CNRS, UMR5558, F-69365 Lyon, France.
[Lasset, Christine] Ctr Leon Berard, Unite Prevent & Epidemiol Genet, F-69373 Lyon, France.
[Leroux, Dominique] CHU Grenoble, Dept Genet, F-38043 Grenoble, France.
[Leroux, Dominique] Univ Grenoble, Inst Albert Bonniot, Grenoble, France.
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RP Antoniou, AC (reprint author), Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England.
EM antonis@srl.cam.ac.uk
RI Ehrencrona, Hans/M-5619-2014; Jakubowska, Anna/O-8050-2014; GLADIEFF,
Laurence/O-5129-2014; Nelen, Marcel/L-4542-2015; Dolcetti,
Riccardo/O-3832-2015; Ligtenberg, Marjolijn/N-9666-2013; Gronwald,
Jacek/A-4576-2017; manoukian, siranoush/E-7132-2017; Peissel,
Bernard/E-8187-2017; Rahman, Nazneen/D-2802-2013; Arnold,
Norbert/E-3012-2010; Toland, Amanda/E-4202-2011; montagna,
marco/E-2225-2012; Giannini, Giuseppe/B-5672-2013; Hoogerbrugge,
Nicoline/O-1016-2013; Radice, Paolo/O-3119-2013; Jansen van Rensburg,
Elizabeth (Lizette)/B-9104-2011; Blanco, Ignacio/D-2565-2013; Leroux,
Dominique/G-7309-2014; Teo, Soo-hwang/H-2353-2014; Osorio,
Ana/I-4324-2014; BYRSKI, Tomasz/I-2844-2014; Oosterwijk, Jan
C./G-5770-2011; Spurdle, Amanda/A-4978-2011;
OI Ehrencrona, Hans/0000-0002-5589-3622; GLADIEFF,
Laurence/0000-0002-6980-9719; Dolcetti, Riccardo/0000-0003-1625-9853;
Ligtenberg, Marjolijn/0000-0003-1290-1474; Gronwald,
Jacek/0000-0002-3643-2871; manoukian, siranoush/0000-0002-6034-7562;
Peissel, Bernard/0000-0001-9233-3571; Janavicius,
Ramunas/0000-0002-3773-8485; Nordling, Margareta/0000-0002-4047-4994;
Rahman, Nazneen/0000-0003-4376-0440; Arnold,
Norbert/0000-0003-4523-8808; montagna, marco/0000-0002-4929-2150;
Giannini, Giuseppe/0000-0003-0299-4056; Blanco,
Ignacio/0000-0002-7414-7481; Osorio, Ana/0000-0001-8124-3984; Eeles,
Rosalind/0000-0002-3698-6241; Barton, David E/0000-0002-2031-9719;
Nathanson, Katherine/0000-0002-6740-0901; Spurdle,
Amanda/0000-0003-1337-7897; PUTIGNANO, Anna Laura/0000-0001-9434-1612;
Nevanlinna, Heli/0000-0002-0916-2976; Kirchhoff,
Tomas/0000-0002-9055-2364; Evans, Gareth/0000-0002-8482-5784; Kruse,
Inken/0000-0001-7176-6300
FU Cancer Research UK [C12292/A11174, C1287/A10118]; European Community
[223175 (HEALTH-F22009-223175)]; Associazione Italiana per la Ricerca
sul Cancro
FX This work was supported by Cancer Research UK grants C12292/A11174 and
C1287/A10118. The research leading to these results has received funding
from the European Community's Seventh Framework Programme under grant
agreement no. 223175 (HEALTH-F22009-223175).
NR 44
TC 42
Z9 42
U1 2
U2 15
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD AUG 15
PY 2011
VL 20
IS 16
BP 3304
EP 3321
DI 10.1093/hmg/ddr226
PG 18
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 796CF
UT WOS:000293027100017
PM 21593217
ER
PT J
AU Berndt, SI
Sampson, J
Yeager, M
Jacobs, KB
Wang, ZM
Hutchinson, A
Chung, C
Orr, N
Wacholder, S
Chatterjee, N
Yu, K
Kraft, P
Feigelson, HS
Thun, MJ
Diver, WR
Albanes, D
Virtamo, J
Weinstein, S
Schumacher, FR
Cancel-Tassin, G
Cussenot, O
Valeri, A
Andriole, GL
Crawford, ED
Haiman, C
Henderson, B
Kolonel, L
Le Marchand, L
Siddiq, A
Riboli, E
Travis, RC
Kaaks, R
Isaacs, W
Isaacs, S
Wiley, KE
Gronberg, H
Wiklund, F
Stattin, P
Xu, JF
Zheng, SL
Sun, JL
Vatten, LJ
Hveem, K
Njolstad, I
Gerhard, DS
Tucker, M
Hayes, RB
Hoover, RN
Fraumeni, JF
Hunter, DJ
Thomas, G
Chanock, SJ
AF Berndt, Sonja I.
Sampson, Joshua
Yeager, Meredith
Jacobs, Kevin B.
Wang, Zhaoming
Hutchinson, Amy
Chung, Charles
Orr, Nick
Wacholder, Sholom
Chatterjee, Nilanjan
Yu, Kai
Kraft, Peter
Feigelson, Heather Spencer
Thun, Michael J.
Diver, W. Ryan
Albanes, Demetrius
Virtamo, Jarmo
Weinstein, Stephanie
Schumacher, Fredrick R.
Cancel-Tassin, Geraldine
Cussenot, Olivier
Valeri, Antoine
Andriole, Gerald L.
Crawford, E. David
Haiman, Christopher
Henderson, Brian
Kolonel, Laurence
Le Marchand, Loic
Siddiq, Afshan
Riboli, Elio
Travis, Ruth C.
Kaaks, Rudolf
Isaacs, William
Isaacs, Sarah
Wiley, Kathleen E.
Gronberg, Henrik
Wiklund, Fredrik
Stattin, Par
Xu, Jianfeng
Zheng, S. Lilly
Sun, Jielin
Vatten, Lars J.
Hveem, Kristian
Njolstad, Inger
Gerhard, Daniela S.
Tucker, Margaret
Hayes, Richard B.
Hoover, Robert N.
Fraumeni, Joseph F., Jr.
Hunter, David J.
Thomas, Gilles
Chanock, Stephen J.
TI Large-scale fine mapping of the HNF1B locus and prostate cancer risk
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; HEPATOCYTE NUCLEAR FACTOR-1-BETA;
SUSCEPTIBILITY LOCI; GENE-EXPRESSION; MULTIPLE LOCI; POPULATION;
VARIANTS; 8Q24; IDENTIFICATION; METAANALYSIS
AB Previous genome-wide association studies have identified two independent variants in HNF1B as susceptibility loci for prostate cancer risk. To fine-map common genetic variation in this region, we genotyped 79 single nucleotide polymorphisms (SNPs) in the 17q12 region harboring HNF1B in 10 272 prostate cancer cases and 9123 controls of European ancestry from 10 case-control studies as part of the Cancer Genetic Markers of Susceptibility (CGEMS) initiative. Ten SNPs were significantly related to prostate cancer risk at a genome-wide significance level of P < 5 x 10(-8) with the most significant association with rs4430796 (P = 1.62 x 10(-24)). However, risk within this first locus was not entirely explained by rs4430796. Although modestly correlated (r(2) = 0.64), rs7405696 was also associated with risk (P = 9.35 x 10(-23)) even after adjustment for rs4430769 (P = 0.007). As expected, rs11649743 was related to prostate cancer risk (P = 3.54 x 10(-8)); however, the association within this second locus was stronger for rs4794758 (P = 4.95 x 10(-10)), which explained all of the risk observed with rs11649743 when both SNPs were included in the same model (P = 0.32 for rs11649743; P = 0.002 for rs4794758). Sequential conditional analyses indicated that five SNPs (rs4430796, rs7405696, rs4794758, rs1016990 and rs3094509) together comprise the best model for risk in this region. This study demonstrates a complex relationship between variants in the HNF1B region and prostate cancer risk. Further studies are needed to investigate the biological basis of the association of variants in 17q12 with prostate cancer.
C1 [Berndt, Sonja I.; Sampson, Joshua; Yeager, Meredith; Wang, Zhaoming; Hutchinson, Amy; Chung, Charles; Orr, Nick; Wacholder, Sholom; Chatterjee, Nilanjan; Yu, Kai; Albanes, Demetrius; Weinstein, Stephanie; Tucker, Margaret; Hoover, Robert N.; Fraumeni, Joseph F., Jr.; Thomas, Gilles; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, US Dept HHS, NIH, Bethesda, MD 20892 USA.
[Yeager, Meredith; Wang, Zhaoming; Hutchinson, Amy; Chung, Charles] NCI, Core Genotyping Facil, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Jacobs, Kevin B.] Bioinformed Consulting Serv, Gaithersburg, MD USA.
[Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA.
[Feigelson, Heather Spencer] Kaiser Permanente, Inst Hlth Res, Denver, CO USA.
[Thun, Michael J.; Diver, W. Ryan] Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Schumacher, Fredrick R.; Haiman, Christopher; Henderson, Brian] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Cancel-Tassin, Geraldine; Cussenot, Olivier; Valeri, Antoine] Hop Tenon, Assistance Publ Hop Paris, Ctr Rech Pathol Prostat, F-75970 Paris, France.
[Andriole, Gerald L.] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA.
[Crawford, E. David] Univ Colorado, Hlth Sci Ctr, Denver, CO USA.
[Crawford, E. David] Univ Colorado, Dept Surg, Denver, CO 80202 USA.
[Kolonel, Laurence; Le Marchand, Loic] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA.
[Siddiq, Afshan; Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Div Epidemiol Publ Hlth & Primary Care, London, England.
[Travis, Ruth C.] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England.
[Kaaks, Rudolf] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Isaacs, William; Isaacs, Sarah; Wiley, Kathleen E.] Johns Hopkins Med Inst, Dept Urol, Baltimore, MD 21205 USA.
[Gronberg, Henrik; Wiklund, Fredrik] Karolinska Inst, CLINTEC, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Stattin, Par] Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden.
[Xu, Jianfeng; Zheng, S. Lilly; Sun, Jielin] Wake Forest Univ, Bowman Gray Sch Med, Ctr Canc Genom, Winston Salem, NC USA.
[Vatten, Lars J.; Hveem, Kristian] Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, N-7034 Trondheim, Norway.
[Gerhard, Daniela S.] NCI, Off Canc Genom, US Dept HHS, NIH, Bethesda, MD 20892 USA.
[Njolstad, Inger] Univ Tromso, Inst Community Med, Tromso, Norway.
[Hayes, Richard B.] NYU, Med Ctr, Dept Environm Med, New York, NY USA.
[Hunter, David J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA.
RP Berndt, SI (reprint author), NCI, Div Canc Epidemiol & Genet, US Dept HHS, NIH, 6120 Execut Blvd,EPS 8116,MSC 7240, Bethesda, MD 20892 USA.
EM berndts@mail.nih.gov
RI Tucker, Margaret/B-4297-2015; Albanes, Demetrius/B-9749-2015;
OI Hayes, Richard/0000-0002-0918-661X; Cancel-Tassin,
Geraldine/0000-0002-9583-6382
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health; National Cancer Institute, National
Institutes of Health [CA129684, HHSN261200800001E]
FX This study was supported by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health and in part by National Cancer Institute,
National Institutes of Health (CA129684 to J.X.) and contract number
HHSN261200800001E.
NR 32
TC 10
Z9 10
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD AUG 15
PY 2011
VL 20
IS 16
BP 3322
EP 3329
DI 10.1093/hmg/ddr213
PG 8
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 796CF
UT WOS:000293027100018
PM 21576123
ER
PT J
AU Martins, AN
Arruda, MB
Aleixo, AW
Pires, AF
Greco, DB
Brindeiro, RD
Tanuri, A
AF Martins, Angelica N.
Arruda, Monica B.
Aleixo, Agdemir W.
Pires, Ana F.
Greco, Dirceu B.
Brindeiro, Rodrigo de M.
Tanuri, Amilcar
TI Prevalence of Etravirine-Associated Mutations in Clinical Samples With
Genotypic Resistance to Nevirapine and Efavirenz in Brazilian Clinics
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE NNRTIs; etravirine; mutations; drug resistance
ID EXPERIENCED HIV-1-INFECTED PATIENTS; PLACEBO-CONTROLLED TRIAL; TMC125
ETRAVIRINE; DOUBLE-BLIND; HIV-1; EFFICACY; SAFETY
AB Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are potent and well tolerated. In Brazil, the first-generation NNRTI efavirenz is included in the majority of first-line antiretroviral treatment regimens. In this study, we evaluated the effectiveness of etravirine, a new second-generation NNRTI, among patients failing antiretroviral regimens containing first-generation NNRTIs. We assessed single resistance mutations to etravirine as well as complex resistance mutations profile and discuss the potential of introducing etravirine as salvage therapy.
C1 [Martins, Angelica N.; Arruda, Monica B.; Pires, Ana F.; Brindeiro, Rodrigo de M.; Tanuri, Amilcar] Univ Fed Rio de Janeiro, Dept Genet, Lab Virol Mol, Rio De Janeiro, Brazil.
[Martins, Angelica N.] NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21701 USA.
[Arruda, Monica B.; Pires, Ana F.] Univ Fed Rio de Janeiro, Dept Biochem, Inst Chem, Rio De Janeiro, Brazil.
[Aleixo, Agdemir W.; Greco, Dirceu B.] Univ Fed Minas Gerais, Lab Imunol & Biol Mol, Infect Dis Serv, Belo Horizonte, MG, Brazil.
[Aleixo, Agdemir W.; Greco, Dirceu B.] Univ Fed Minas Gerais, Sch Med, Belo Horizonte, MG, Brazil.
RP Tanuri, A (reprint author), Univ Fed Rio de Janeiro, Dept Genet, Lab Virol Mol, Rio De Janeiro, Brazil.
EM atanuri@biologia.ufrj.br
RI Imunologia, Inct/I-2124-2013
FU Ministry of Health/Secretariat of Health Surveillance/Department of STD,
AIDS and Viral Hepatitis through Brazilian Government [AD/BRA/03/H34];
Ministry of Health/Secretariat of Health Surveillance/Department of STD,
AIDS and Viral Hepatitis through United Nations Office on Drugs and
Crime UNODC [AD/BRA/03/H34]; State Science Foundation of Rio de Janeiro
(FAPERJ); Brazilian Council for Scientific and Technologic Development
(CNPq); CAPES
FX This work was carried out by the UFRJ and UFMG with technical and
financial support of the Ministry of Health/Secretariat of Health
Surveillance/Department of STD, AIDS and Viral Hepatitis through the
Project of International Technical Cooperation AD/BRA/03/H34 between the
Brazilian Government and the United Nations Office on Drugs and Crime
UNODC; and also received support from State Science Foundation of Rio de
Janeiro (FAPERJ), the Brazilian Council for Scientific and Technologic
Development (CNPq), and CAPES.
NR 10
TC 2
Z9 2
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD AUG 15
PY 2011
VL 57
SU 3
BP S193
EP S196
DI 10.1097/QAI.0b013e31821e9cf6
PG 4
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 798TU
UT WOS:000293235900011
PM 21857317
ER
PT J
AU McGuire, V
Van den Eeden, SK
Tanner, CM
Kamel, F
Umbach, DM
Marder, K
Mayeux, R
Ritz, B
Ross, GW
Petrovitch, H
Topol, B
Popat, RA
Costello, S
Manthripragada, AD
Southwick, A
Myers, RM
Nelson, LM
AF McGuire, V.
Van den Eeden, S. K.
Tanner, C. M.
Kamel, F.
Umbach, D. M.
Marder, K.
Mayeux, R.
Ritz, B.
Ross, G. W.
Petrovitch, H.
Topol, B.
Popat, R. A.
Costello, S.
Manthripragada, A. D.
Southwick, A.
Myers, R. M.
Nelson, L. M.
TI Association of DRD2 and DRD3 polymorphisms with Parkinson's disease in a
multiethnic consortium
SO JOURNAL OF THE NEUROLOGICAL SCIENCES
LA English
DT Article
DE Parkinson's disease; Dopamine receptor genes; Case-control studies;
Epidemiology
ID DOPAMINE-RECEPTOR; GENE; SUSCEPTIBILITY; SMOKING; ANKK1; DEPENDENCE;
AMERICAN; BEHAVIOR; TTC12; NCAM1
AB Objective: To examine genetic associations of polymorphisms in the dopamine receptor D2 (DRD2) and D3 (DRD3) genes with risk of Parkinson's disease (PD).
Methods: The study included 1325 newly diagnosed patients with PD and 1735 controls from a consortium of five North American case-control studies. We collected risk factor information by in-person or telephone interview. Six DRD2 and two DRD3 polymorphisms were genotyped using a common laboratory. Odds ratios were estimated using logistic regression.
Results: Among non-Hispanic whites, homozygous carriers of Taq1A DRD2 (rs1800497) polymorphism had an increased risk of PD compared to homozygous wildtype carriers (OR = 1.5, 95% CI 1.0-2.3). In contrast, the direction of association for Taq1A polymorphism was opposite for African-Americans, showing an inverse association with PD risk (OR = 0.10, 95% CI 0.2-0.7). Among white Hispanics who carried two alleles, the Ser9Gly DRD3 (rs6280) polymorphism was associated with a decreased risk of PD (OR = 0.4, 95% CI 0.2-0.8). The inverse association of smoking with PD risk was not modified by any of the DRD2 or DRD3 polymorphisms.
Conclusions: DRD2 polymorphisms are unlikely to be true disease-causing variants; however, three DRD2 polymorphisms (including Taq1A) may be in linkage disequilibrium with possible disease associated variants in the DRD2-ANKK1-NCAM1-TTC12 gene cluster. (C) 2011 Elsevier B.V. All rights reserved.
C1 [McGuire, V.; Topol, B.; Popat, R. A.; Nelson, L. M.] Stanford Univ, Dept Hlth Res & Policy, Sch Med, Div Epidemiol, Stanford, CA 94305 USA.
[Van den Eeden, S. K.] Kaiser Fdn Res Inst, Div Res, Oakland, CA USA.
[Tanner, C. M.] Parkinsons Inst, Sunnyvale, CA USA.
[Kamel, F.] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA.
[Umbach, D. M.] Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC USA.
[Marder, K.; Mayeux, R.] Columbia Univ, Coll Phys & Surg, Dept Neurol, New York, NY USA.
[Marder, K.; Mayeux, R.] Columbia Univ, Gertrude H Sergievsky Ctr, Coll Phys & Surg, New York, NY 10027 USA.
[Marder, K.; Mayeux, R.] Columbia Univ, Coll Phys & Surg, Taub Inst, New York, NY USA.
[Ritz, B.; Costello, S.; Manthripragada, A. D.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA.
[Ross, G. W.; Petrovitch, H.] Vet Affairs Pacific Isl Hlth Care Syst, Honolulu, HI USA.
[Ross, G. W.; Petrovitch, H.] Pacific Hlth Res Inst, Honolulu, HI USA.
[Costello, S.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA.
[Manthripragada, A. D.] US FDA, Rockville, MD 20857 USA.
[Southwick, A.; Myers, R. M.] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA.
RP McGuire, V (reprint author), Stanford Univ, Dept Hlth Res & Policy, Sch Med, Div Epidemiol, HRP Redwood Bldg,Room T213C, Stanford, CA 94305 USA.
EM vmcguire@stanford.edu
RI Ritz, Beate/E-3043-2015;
OI Kamel, Freya/0000-0001-5052-6615
FU Michael J. Fox Foundation for Parkinson's Research; NIH [NS R01-31964,
ES R03-13970, R01-NS32527, ES10544]; Tobacco-Related Disease Research
Fund [8RT-0131, 11RT-0237]; SCEHSC [5P30 ES07048]; Parkinson's Disease
Association; United States Department of the Army [DAMD17-98-1-8621, NIA
NO1-AG-4-2149, NINDSR01-NS41265, NHLBINO1-HC-05102]; Office of Research
and Development, Medical Research Service, Veterans Affairs; NIH; NCI
(Division of Cancer Epidemiology and Genetics) [U54-ES12077]; [NIAPO1
AG07232]; [U54-ES12078]; [NIEHS01-ES10803]
FX Funding was provided to the PEGASUS genetic consortium by the Michael J.
Fox Foundation for Parkinson's Research. Additional funding to
individual investigators for the original studies was provided by: NIH
NS R01-31964, NIH ES R03-13970, and Tobacco-Related Disease Research
Fund Grants 8RT-0131 and 11RT-0237 (Dr. Lorene Nelson,); NIH R01-NS32527
(Drs. Richard Mayeux and Karen Marder), NIAPO1 AG07232 (Dr. Richard
Mayeux); NIH ES10544 and U54-ES12078, pilot funding from SCEHSC # 5P30
ES07048, the Parkinson's Disease Association (Dr. Beate Ritz); United
States Department of the Army-DAMD17-98-1-8621, NIA NO1-AG-4-2149,
NINDSR01-NS41265, NHLBINO1-HC-05102, and Office of Research and
Development, Medical Research Service, Veterans Affairs (Dr. G. Webster
Ross); NIEHS01-ES10803 and NIH intramural funding to NIEHS (Epidemiology
Branch) and NCI (Division of Cancer Epidemiology and Genetics)
U54-ES12077 (Drs. Caroline Tanner and Freya Kamel). The information in
this paper does not necessarily reflect the position or the policy of
the government and no official endorsement should be inferred.
NR 29
TC 15
Z9 16
U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-510X
J9 J NEUROL SCI
JI J. Neurol. Sci.
PD AUG 15
PY 2011
VL 307
IS 1-2
BP 22
EP 29
DI 10.1016/j.jns.2011.05.031
PG 8
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 796KF
UT WOS:000293049500005
PM 21663922
ER
PT J
AU Kim, YM
Jang, WH
Quezado, MM
Oh, Y
Chung, KC
Junn, E
Mouradian, MM
AF Kim, Yong Man
Jang, Won Hee
Quezado, Martha M.
Oh, Yohan
Chung, Kwang Chul
Junn, Eunsung
Mouradian, M. Maral
TI Proteasome inhibition induces alpha-synuclein SUMOylation and aggregate
formation
SO JOURNAL OF THE NEUROLOGICAL SCIENCES
LA English
DT Article
DE Parkinson's disease; Dementia with Lewy Bodies; alpha-Synuclein;
SUMOylation; Protein aggregation; Proteasome
ID PARKINSONS-DISEASE; ENHANCED SUMOYLATION; SUMO MODIFICATION; LEWY
BODIES; PROTEIN; PHOSPHORYLATION; CONSEQUENCES; DEGRADATION;
CONJUGATION; NITRATION
AB Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB) are characterized pathologically by intraneuronal inclusions called Lewy bodies (LBs) and Lewy neurites. A major component of these inclusions is the protein a-synuclein, which is natively unfolded but forms oligomers and insoluble fibrillar aggregates under pathological conditions. Although alpha-synuclein is known to undergo several posttranslational modifications, the contribution of SUMOylation to alpha-synuclein aggregation and the pathogenesis of alpha-synucleinopathies have not been elucidated. Here, we provide evidence that aggregates and inclusions formed as a result of impaired proteasome activity contain SUMOylated alpha-synuclein. Additionally, SUMO1 is present in the halo of LBs colocalizing with alpha-synuclein in the brains of PD and DLB patients. Interestingly. SUMOylation does not affect the ubiquitination of alpha-synuclein. These findings suggest that proteasomal dysfunction results in the accumulation of SUMOylated alpha-synuclein and subsequently its aggregation, pointing to the contribution of this posttranslational modification to the pathogenesis of inclusion formation in alpha-synucleinopathies. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Jang, Won Hee; Junn, Eunsung; Mouradian, M. Maral] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurol, Ctr Neurodegenerat & Neuroimmunol Dis, Piscataway, NJ 08854 USA.
[Kim, Yong Man] FCB Pharmicell, Songnam 462806, Gyeonggi Do, South Korea.
[Quezado, Martha M.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Oh, Yohan; Chung, Kwang Chul] Yonsei Univ, Coll Life Sci & Biotechnol, Dept Biol, Seoul 120749, South Korea.
RP Mouradian, MM (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurol, Ctr Neurodegenerat & Neuroimmunol Dis, 683 Hoes Lane W,Room 180, Piscataway, NJ 08854 USA.
EM Mouradian@umdnj.edu
OI Mouradian, M. Maral/0000-0002-9937-412X
FU US NIH [Z01NS002826]
FX This study was supported in part by the US NIH intramural program
(Z01NS002826) to M. M. M. who is currently the William Dow Lovett
Professor of Neurology.
NR 34
TC 28
Z9 28
U1 1
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-510X
J9 J NEUROL SCI
JI J. Neurol. Sci.
PD AUG 15
PY 2011
VL 307
IS 1-2
BP 157
EP 161
DI 10.1016/j.jns.2011.04.015
PG 5
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 796KF
UT WOS:000293049500029
PM 21641618
ER
PT J
AU Brock, KE
Huang, WY
Fraser, DR
Ke, L
Tseng, M
Mason, RS
Stolzenberg-Solomon, RZ
Freedman, DM
Ahn, J
Peters, U
McCarty, C
Hollis, BW
Ziegler, RG
Purdue, MP
Graubard, BI
AF Brock, Kaye E.
Huang, Wen-Yi
Fraser, David R.
Ke, Liang
Tseng, Marilyn
Mason, Rebecca S.
Stolzenberg-Solomon, Rachael Z.
Freedman, D. Michal
Ahn, Jiyoung
Peters, Ulrike
McCarty, Catherine
Hollis, Bruce W.
Ziegler, Regina G.
Purdue, Mark P.
Graubard, Barry I.
TI Diabetes prevalence is associated with serum 25-hydroxyvitamin D and
1,25-dihydroxyvitamin D in US middle-aged Caucasian men and women: a
cross-sectional analysis within the Prostate, Lung, Colorectal and
Ovarian Cancer Screening Trial
SO BRITISH JOURNAL OF NUTRITION
LA English
DT Article
DE Diabetes; Vitamin D status; 25-Hydroxyvitamin D; 1,25-Dihydroxyvitamin D
ID VITAMIN-D STATUS; BODY-MASS INDEX; CARDIOVASCULAR-DISEASE; D DEFICIENCY;
INSULIN; ADULTS; HEALTH; RADIOIMMUNOASSAY; CALCIUM
AB Hypovitaminosis D may be associated with diabetes, hypertension and CHD. However, because studies examining the associations of all three chronic conditions with circulating 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) are limited, we examined these associations in the US Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial (n 2465). Caucasian PLCO participants selected as controls in previous nested case control studies of 25(OH)D and 1,25(OH)(2)D were included in this analysis. Diabetes, CHD and hypertension prevalence, risk factors for these conditions and intake of vitamin 1) and Ca were collected from a baseline questionnaire. Results indicated that serum levels of 25(OH)D were low (<50 nmol/l) in 29% and very low (<37 nmol/l) in 11% of subjects. The prevalence of diabetes, hypertension and CHD was 7, 30 and 10%, respectively. After adjustment for confounding by sex, geographical location, educational level, smoking history, BMI, physical activity, total dietary energy and vitamin D and Ca intake, only diabetes was significantly associated with lower 25(OH)D and 1,25(OH)(2)D levels. Caucasians who had 25(OH)D >= nmol/l were half as likely to have diabetes (OR 0.5 (95% CI 0.3, 0.9)) compared with those who had 25(OH)D <37 nmol/l. Those in the highest quartile of 1,25(OH)(2)D (>= 103 pmol/l) were less than half as likely to have diabetes (OR 0.3 (95% Cl 0.1, 0.7)) than those in the lowest quartile (<72 pmol/l). In conclusion, the independent associations of 25(OH)D and 1,25(OH)(2)D with diabetes prevalence in a large population are new findings, and thus warrant confirmation in larger, prospective studies.
C1 [Brock, Kaye E.; Ke, Liang] Univ Sydney, Fac Hlth Sci, Lidcombe, NSW, Australia.
[Huang, Wen-Yi; Stolzenberg-Solomon, Rachael Z.; Freedman, D. Michal; Ziegler, Regina G.; Purdue, Mark P.; Graubard, Barry I.] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
[Fraser, David R.] Univ Sydney, Fac Vet Sci, Camperdown, NSW, Australia.
[Ke, Liang] George Inst, Dept Res & Dev, Beijing, Peoples R China.
[Tseng, Marilyn] Calif Polytech State Univ San Luis Obispo, Dept Kinesiol, San Luis Obispo, CA 93407 USA.
[Mason, Rebecca S.] Univ Sydney, Fac Med, Bosch Inst, Camperdown, NSW, Australia.
[Ahn, Jiyoung] NYU Sch Med, Dept Environm Med, Div Epidemiol, New York, NY USA.
[Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[McCarty, Catherine] Marshfield Clin Res Fdn, Marshfield, WI USA.
[Hollis, Bruce W.] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA.
RP Brock, KE (reprint author), Univ Sydney, Fac Hlth Sci, Lidcombe, NSW, Australia.
EM kaye.brock@sydney.edu.au
RI Tseng, Marilyn/B-9334-2016; Purdue, Mark/C-9228-2016
OI Tseng, Marilyn/0000-0002-9969-9055; Purdue, Mark/0000-0003-1177-3108
FU National Cancer Institute (NCI), the National Institutes of Health
(NIH); US Public Health Service, NCI, NIH, the Department of Health and
Human Services
FX This research was supported in part by the Intramural Research Program
of the National Cancer Institute (NCI), the National Institutes of
Health (NIH). In addition, this research was supported by US Public
Health Service contracts from NCI, NIH, the Department of Health and
Human Services. All authors reviewed the final manuscript before
submission, and none has a conflict of interest with regard to this
work. K. E. B. was primary author in analysing the data and preparing
the manuscript and coordinating the co-authors; R. Z. S.-S., D. M. F.,
J. A., U. P., C. M., R. G. Z. and M. P. P. were the primary
investigators in the initial nested case-control studies used for this
analysis and W.-Y. H. and M. P. P. are the overall co-ordinators of
Prostate, Lung, Colorectal and Ovarian Screening Trial data, D. R. F.
and R. S. M. and B. W. H. were involved in the vitamin D analysis
aspects of the study; K. E. B., L. K. and B. I. G. were involved in the
data analysis, and although K. E. B., M. T. and B. I. G. prepared the
manuscript, all co-authors read and contributed to the final version,
especially D. R. F. and R. S. M. read the vitamin D metabolism aspects.
NR 24
TC 18
Z9 19
U1 0
U2 8
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 0007-1145
J9 BRIT J NUTR
JI Br. J. Nutr.
PD AUG 14
PY 2011
VL 106
IS 3
BP 339
EP 344
DI 10.1017/S0007114511001590
PG 6
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 797VO
UT WOS:000293158400006
PM 21736838
ER
PT J
AU Holmes, MV
Newcombe, P
Hubacek, JA
Sofat, R
Ricketts, SL
Cooper, J
Breteler, MMB
Bautista, LE
Sharma, P
Whittaker, JC
Smeeth, L
Fowkes, FGR
Algra, A
Shmeleva, V
Szolnoki, Z
Roest, M
Linnebank, M
Zacho, J
Nalls, MA
Singleton, AB
Ferrucci, L
Hardy, J
Worrall, BB
Rich, SS
Matarin, M
Norman, PE
Flicker, L
Almeida, OP
van Bockxmeer, FM
Shimokata, H
Khaw, KT
Wareham, NJ
Bobak, M
Sterne, JAC
Smith, GD
Talmud, PJ
van Duijn, C
Humphries, SE
Price, JF
Ebrahim, S
Lawlor, DA
Hankey, GJ
Meschia, JF
Sandhu, MS
Hingorani, AD
Casas, JP
AF Holmes, Michael V.
Newcombe, Paul
Hubacek, Jaroslav A.
Sofat, Reecha
Ricketts, Sally L.
Cooper, Jackie
Breteler, Monique M. B.
Bautista, Leonelo E.
Sharma, Pankaj
Whittaker, John C.
Smeeth, Liam
Fowkes, F. Gerald R.
Algra, Ale
Shmeleva, Veronika
Szolnoki, Zoltan
Roest, Mark
Linnebank, Michael
Zacho, Jeppe
Nalls, Michael A.
Singleton, Andrew B.
Ferrucci, Luigi
Hardy, John
Worrall, Bradford B.
Rich, Stephen S.
Matarin, Mar
Norman, Paul E.
Flicker, Leon
Almeida, Osvaldo P.
van Bockxmeer, Frank M.
Shimokata, Hiroshi
Khaw, Kay-Tee
Wareham, Nicholas J.
Bobak, Martin
Sterne, Jonathan A. C.
Smith, George Davey
Talmud, Philippa J.
van Duijn, Cornelia
Humphries, Steve E.
Price, Jackie F.
Ebrahim, Shah
Lawlor, Debbie A.
Hankey, Graeme J.
Meschia, James F.
Sandhu, Manjinder S.
Hingorani, Aroon D.
Casas, Juan P.
TI Effect modification by population dietary folate on the association
between MTHFR genotype, homocysteine, and stroke risk: a meta-analysis
of genetic studies and randomised trials
SO LANCET
LA English
DT Article
ID CORONARY-HEART-DISEASE; METHYLENETETRAHYDROFOLATE-REDUCTASE GENE;
FOLIC-ACID SUPPLEMENTATION; STAGE RENAL-DISEASE; CARDIOVASCULAR-DISEASE;
B-VITAMINS; ISCHEMIC-STROKE; PLASMA HOMOCYSTEINE; C677T POLYMORPHISM;
VASCULAR-DISEASE
AB Background The MTHFR 677C -> T polymorphism has been associated with raised homocysteine concentration and increased risk of stroke. A previous overview showed that the effects were greatest in regions with low dietary folate consumption, but differentiation between the effect of folate and small-study bias was difficult. A meta-analysis of randomised trials of homocysteine-lowering interventions showed no reduction in coronary heart disease events or stroke, but the trials were generally set in populations with high folate consumption. We aimed to reduce the effect of small-study bias and investigate whether folate status modifies the association between MTHFR 677C -> T and stroke in a genetic analysis and meta-analysis of randomised controlled trials.
Methods We established a collaboration of genetic studies consisting of 237 datasets including 59 995 individuals with data for homocysteine and 20 885 stroke events. We compared the genetic findings with a meta-analysis of 13 randomised trials of homocysteine-lowering treatments and stroke risk (45 549 individuals, 2314 stroke events, 269 transient ischaemic attacks).
Findings The effect of the MTHFR 677C -> T variant on homocysteine concentration was larger in low folate regions (Asia; difference between individuals with TT versus CC genotype, 3.12 mu mol/L, 95% CI 2.23 to 4.01) than in areas with folate fortification (America, Australia, and New Zealand, high; 0.13 mu mol/L, -0.85 to 1.11). The odds ratio (OR) for stroke was also higher in Asia (1.68, 95% CI 1.44 to 1.97) than in America, Australia, and New Zealand, high (1.03, 0.84 to 1.25). Most randomised trials took place in regions with high or increasing population folate concentrations. The summary relative risk (RR) of stroke in trials of homocysteine-lowering interventions (0 94, 95% CI 085 to 1.04) was similar to that predicted for the same extent of homocysteine reduction in large genetic studies in populations with similar folate status (predicted RR 1.00, 95% CI 0.90 to 1.11). Although the predicted effect of homocysteine reduction from large genetic studies in low folate regions (Asia) was larger (RR 0.78, 95% CI 0.68 to 0.90), no trial has evaluated the effect of lowering of homocysteine on stroke risk exclusively in a low folate region.
Interpretation In regions with increasing levels or established policies of population folate supplementation, evidence from genetic studies and randomised trials is concordant in suggesting an absence of benefit from lowering of homocysteine for prevention of stroke. Further large-scale genetic studies of the association between MTHFR 677C -> T and stroke in low folate settings are needed to distinguish effect modification by folate from small-study bias. If future randomised trials of homocysteine-lowering interventions for stroke prevention are undertaken, they should take place in regions with low folate consumption.
C1 [Holmes, Michael V.; Bobak, Martin; Hingorani, Aroon D.; Casas, Juan P.] UCL, Res Dept Epidemiol & Publ Hlth, London, England.
[Sofat, Reecha; Hingorani, Aroon D.] UCL, Dept Clin Pharmacol, London, England.
[Cooper, Jackie; Talmud, Philippa J.; Humphries, Steve E.] UCL, Inst Cardiovasc Sci, Ctr Cardiovasc Genet, London, England.
[Matarin, Mar] UCL, Dept Clin & Expt Epilepsy, London, England.
[Hardy, John] UCL, Inst Neurol, London, England.
[Newcombe, Paul; Whittaker, John C.; Smeeth, Liam; Ebrahim, Shah; Casas, Juan P.] London Sch Hyg & Trop Med, Fac Epidemiol & Publ Hlth, London WC1E 7HT, England.
[Newcombe, Paul; Whittaker, John C.] GlaxoSmithKline, Genet, R&D, Stevenage, Herts, England.
[Hubacek, Jaroslav A.] Inst Clin & Expt Med, Prague, Czech Republic.
[Hubacek, Jaroslav A.] Cardiovasc Res Ctr, Prague, Czech Republic.
[Ricketts, Sally L.] Univ Cambridge, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Cambridge, England.
[Khaw, Kay-Tee] Univ Cambridge, Sch Clin Med, Clin Gerontol Unit, Cambridge, England.
[Wareham, Nicholas J.] Univ Cambridge, MRC Epidemiol Unit, Inst Metab Sci, Cambridge, England.
[Sandhu, Manjinder S.] Wellcome Trust Sanger Inst, Genet Epidemiol Grp, Cambridge, England.
[Breteler, Monique M. B.; van Duijn, Cornelia] Univ Med Ctr, Dept Epidemiol, Erasmus MC, Rotterdam, Netherlands.
[Breteler, Monique M. B.] German Ctr Neurodegenerat Dis DZNE, Bonn, Germany.
[Bautista, Leonelo E.] Univ Wisconsin, Dept Populat Hlth Sci, Sch Med & Publ Hlth, Madison, WI USA.
[Sharma, Pankaj] Univ London Imperial Coll Sci Technol & Med, ICCRU, London, England.
[Fowkes, F. Gerald R.; Price, Jackie F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
[Algra, Ale] Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.
[Shmeleva, Veronika] Russian Inst Haematol & Transfus, St Petersburg, Russia.
[Szolnoki, Zoltan] Pandy Cty Hosp, Dept Neurol, Gyula, Hungary.
[Algra, Ale] Univ Med Ctr Utrecht, Utrecht Stroke Ctr, Dept Neurol, Utrecht, Netherlands.
[Algra, Ale] Univ Med Ctr Utrecht, Julius Ctr, Utrecht, Netherlands.
[Roest, Mark] Univ Med Ctr Utrecht, Dept Clin Chem & Haematol, Utrecht, Netherlands.
[Linnebank, Michael] Univ Zurich Hosp, Dept Neurol, CH-8091 Zurich, Switzerland.
[Zacho, Jeppe] Herlev Univ Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark.
[Nalls, Michael A.; Singleton, Andrew B.] NIA, Neurogenet Lab, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Ferrucci, Luigi] NIA, Baltimore, MD 21224 USA.
[Worrall, Bradford B.] Univ Virginia, Dept Neurol, Charlottesville, VA USA.
[Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
[Norman, Paul E.] Univ Western Australia, Sch Surg, Perth, WA 6009, Australia.
[Flicker, Leon; Hankey, Graeme J.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia.
[Almeida, Osvaldo P.] Univ Western Australia, Sch Psychiat & Clin Neurosci, Perth, WA 6009, Australia.
[van Bockxmeer, Frank M.] Univ Western Australia, Sch Pathol & Lab Med, Perth, WA 6009, Australia.
[Flicker, Leon; Almeida, Osvaldo P.] WACHA, Western Australia Inst Med Res, Perth, WA, Australia.
[Almeida, Osvaldo P.] Royal Perth Hosp, Dept Psychiat, Perth, WA, Australia.
[van Bockxmeer, Frank M.] Royal Perth Hosp, Cardiovasc Genet Lab, Div Lab Med, Perth, WA, Australia.
[Shimokata, Hiroshi] Natl Ctr Geriatr & Gerontol, Obu City, Japan.
[Smith, George Davey; Lawlor, Debbie A.] Univ Bristol, MRC Ctr Causal Anal Translat Epidemiol, Bristol, Avon, England.
[Sterne, Jonathan A. C.] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England.
[Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA.
RP Casas, JP (reprint author), London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, London WC1E 7HT, England.
EM juan.pablo-casas@lshtm.ac.uk
RI Singleton, Andrew/C-3010-2009; Almeida, Osvaldo/A-4925-2008; Hardy,
John/C-2451-2009; Norman, Paul/C-5485-2013; Hankey, Graeme /H-4968-2014;
Matarin, Mar/F-1771-2016; Davey Smith, George/A-7407-2013
OI Talmud, Philippa/0000-0002-5560-1933; Monsalve, Beatriz
Elena/0000-0002-5994-866X; Humphries, Stephen E/0000-0002-8221-6547;
Lawlor, Debbie A/0000-0002-6793-2262; Norman, Paul/0000-0003-3406-0506;
Hankey, Graeme /0000-0002-6044-7328; Matarin, Mar/0000-0002-4717-5735;
Davey Smith, George/0000-0002-1407-8314
FU GlaxoSmithKline; AstraZeneca; Bayer; Boehringer Ingelheim; Merck Serono;
Eisai; Johnson Johnson; NIH; Sanofi-Aventis; Sobering-Plough; Pfizer;
Medical Research Council [G0802432, G0600580, 00023001]; British Heart
Foundation [FS/07/011, FS05/125, RG/08/008]; Erasmus Medical Center and
Erasmus University, Rotterdam; Netherlands Organization for Health
Research and Development; Netherlands Organisation for Scientific
Research; Research Institute for Diseases in the Elderly; Ministry of
Education, Culture and Science; Ministry for Health, Welfare and Sports;
European Commission; Municipality of Rotterdam; UK Department of Health;
Wellcome Trust [082178]; Netherlands Heart Foundation [2001.06g]; Brain
Foundation Netherlands [gF01.15]; Danish Medical Research Council;
Danish Heart Foundation; Chief Physician Johan Boserup and Use Boserup's
Fund; US National Institute of Neurological Disorders and Stroke [R01
NS39987, R01 NS42733]; National Institute on Aging, National Institutes
of Health, Department of Health and Human Services [Z01 AG000015-50, Z01
AG000954-06, 2003-078]; National Center for Geriatrics and Gerontology,
Japan [23-33]; National Health and Medical Research Council of Australia
[279408, 379600, 403963, 513823]; Wellcome Trust; US National Institute
of Aging; UK Medical Research Council [G0600705]; University of Bristol;
British Heart Foundation Chair of Cardiovascular Genetics; Department of
Health
FX PN is a full-time employee of GlaxoSmithKline. PS has received honoraria
for lecturing in industry-sponsored meetings and has received industry
funding for attending national and international meetings. He has also
received research grants from pharmaceutical companies and has been a
paid consultant to the biotech industry and a member of industry
advisory boards. JCW owns shares in GlaxoSmithlaine and is 90% employed
at GlaxoSmithKline while retaining a 10% appointment at the London
School of Hygiene and Tropical Medicine. LS has received consultancy
fees from GlaxoSmithKline. FGRF has received funding from AstraZeneca
for consultancy and grants from Bayer. AA received fees from Boehringer
Ingelheim for consultancy, speaker fees, and participation in
international advisory board meetings. He is a principal investigator of
ESPIRIT, the European/Australian Stroke Prevention in Reversible
Ischaemia Trial, a trial that was run independently of any
pharmaceutical company, and in 2006, after completion and full analysis
of ESPRIT, the study group accepted financial support from Boehringer
Ingelheim for post-hoc exploratory analyses of the ESPRIT trial data.
For this purpose a contract was signed in negotiated complete scientific
freedom. ML has received money for board membership, consultancy, expert
testimony, grants, and lectures from various pharmaceutical companies.
JH has received consultancy fees from Merck Serono, Eisai, and Johnson &
Johnson. BBW is co-principal investigator of the NIH funded GARNET,
which funds genome-wide association studies of genetic samples from the
Vitamin Intervention as Stroke Prevention randomised controlled trial.
GH has received funds from Johnson & Johnson (executive committee for
ROCKET-AF trial); Sanofi-Aventis (executive committee BOREALIS trial);
Sobering-Plough (steering committee TRA 2P TIMI 50 trial); Pradaxa
(dabigatran) advisory board, Australia; and payment for lectures at
sponsored scientific symposia by Sanofi-Aventis and Pfizer.; We thank
Robert Clarke, Sarah Parish, and Derrick A Bennett (Clinical Trial
Service Unit and Epidemiological Studies Unit, University of Oxford, UK)
for their insightful comments and advice; Barbara Voetsch, Yiingdong
Zhang, Nina Salooja, Myeong-Kyu Kim, Hugh Markus, Ahamad Hassan, Koichi
Miyaki, Jose Maria Grasa Ullrich, Belen Sanchez, Hui Rutai, Emel Gurkan,
Nam Keun Kim, Tomohiro Katsuya, Ravindra Varma Alluri, Renu Saxena,
Larry Baum, Kostantinos Kostulas, Fahri Ucar, Ali Sazci, Byung-Ok Choi,
Yan Zhen Zheng, Christine Mannhalter, Bossella Marcucci, Alessandro
Pezzini, John Eikelboom, Xin Fang, Use Lotte Husemoen, and Hiroki Narnba
for providing relevant information about the genotype frequencies,
homocysteine, and folic acid concentrations from their studies; and Dave
Leon for his valuable comments on the report. Funding for this study was
from: a Population Health Scientist Fellowship, Medical Research Council
(G0802432; MVH); the Medical Research Council (G0600580; PN); Project
00023001 (IKEM; JAI-I); British Heart Foundation (Schillingford)
clinical training fellowship (FS/07/011; RS); British Heart Foundation
(SLR, FP); Erasmus Medical Center and Erasmus University, Rotterdam, The
Netherlands Organization for Health Research and Development, The
Netherlands Organisation for Scientific Research, 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), and the Municipality of Rotterdam (The Rotterdam
Study; MMMB, CVD); UK Department of Health Senior Fellowship (PS);
Senior Clinical Fellowship from the Wellcome Trust (082178, LS); British
Heart Foundation (Edinburgh Artery Study, FGRF); the Netherlands Heart
Foundation (2001.06g) and the Brain Foundation Netherlands (gF01.15; the
RATIO Study; AA); the Danish Medical Research Council, the Danish Heart
Foundation, and Chief Physician Johan Boserup and Use Boserup's Fund
(JZ); the US National Institute of Neurological Disorders and Stroke,
grant numbers R01 NS39987 and R01 NS42733 (ISGS and SWISS: MAN, ABS, LF,
JH, BBW, SR, MM, J FM); Intramural Research Program of the National
Institute on Aging, National Institutes of Health, Department of Health
and Human Services (LF; project numbers Z01 AG000015-50 and Z01
AG000954-06, human subjects protocol number 2003-078; portions of this
study used the high-performance computational capabilities of the
Biowulf Linux cluster at the National Institutes of Health); Research
Funding for Longevity Sciences (23-33) from the National Center for
Geriatrics and Gerontology, Japan (HS); the National Health and Medical
Research Council of Australia (the Health In Men Study, project grants
279408, 379600, 403963, and 513823; PEN, LF, OA, FvB, GH); Wellcome
Trust and the US National Institute of Aging (the HAPIEE study; MB); the
UK Medical Research Council (G0600705) and the University of Bristol
(GDS and DAL); British Heart Foundation Chair of Cardiovascular Genetics
(SD); British Heart Foundation Senior Fellowship (FS05/125; ADH);
British Heart Foundation (RG/08/008; SEH, PJT, ADH); and the Department
of Health Policy Research Programme and British Heart Foundation (the
British Women's Heart and Health Study; SE). The views expressed in the
publication are those of the authors and not necessarily those of any
funding bodies.
NR 62
TC 133
Z9 147
U1 4
U2 36
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD AUG 13
PY 2011
VL 378
IS 9791
BP 584
EP 594
DI 10.1016/S0140-6736(11)60872-6
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 812UX
UT WOS:000294319500030
PM 21803414
ER
PT J
AU Ahn, B
Bohr, VA
AF Ahn, Byungchan
Bohr, Vilhelm A.
TI DNA secondary structure of the released strand stimulates WRN helicase
action on forked duplexes without coordinate action of WRN exonuclease
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE WRN helicases; DNA secondary structure; DNA unwinding
ID WERNER-SYNDROME PROTEIN; SYNDROME CELLS; INTERACTS; DAMAGE; PHENOTYPE;
SUBSTRATE; BINDING
AB Werner syndrome (WS) is an autosomal recessive premature aging disorder characterized by aging-related phenotypes and genomic instability. WS is caused by mutations in a gene encoding a nuclear protein, Werner syndrome protein (WRN), a member of the RecQ helicase family, that interestingly possesses both helicase and exonuclease activities. Previous studies have shown that the two activities act in concert on a single substrate. We investigated the effect of a DNA secondary structure on the two WRN activities and found that a DNA secondary structure of the displaced strand during unwinding stimulates WRN helicase without coordinate action of WRN exonuclease. These results imply that WRN helicase and exonuclease activities can act independently, and we propose that the uncoordinated action may be relevant to the in vivo activity of WRN. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Ahn, Byungchan] Univ Ulsan, Dept Life Sci, Ulsan 680749, South Korea.
[Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, Biomed Res Ctr, Baltimore, MD 21224 USA.
RP Ahn, B (reprint author), Univ Ulsan, Dept Life Sci, Ulsan 680749, South Korea.
EM bbccahn@mail.ulsan.ac.kr
FU University of Ulsan; Ministry of Education, Science and Technology
[2009-0094050]
FX This work was supported by the research fund of the University of Ulsan
to B. Ahn (2007). This work was supported by Priority Research Center
Program through the National Research Foundation of Korea (NRF) funded
by the Ministry of Education, Science and Technology (2009-0094050).
NR 27
TC 2
Z9 2
U1 1
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD AUG 12
PY 2011
VL 411
IS 4
BP 684
EP 689
DI 10.1016/j.bbrc.2011.06.184
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 812UB
UT WOS:000294317300006
PM 21763283
ER
PT J
AU Tanaka, H
Mine, T
Ogasa, H
Taguchi, T
Liang, CT
AF Tanaka, H.
Mine, T.
Ogasa, H.
Taguchi, T.
Liang, C. T.
TI Expression of RANKL/OPG during bone remodeling in vivo
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Bone remodeling; Receptor activator of nuclear factor kappa B ligand
(RANKL); Osteoprotegerin (OPG)
AB The interaction between receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) plays a dominant role in osteoclastogenesis. As both proteins are produced by osteoblast lineage cells, they are considered to represent a key link between bone formation and resorption. In this study, we investigated the expression of RANKL and OPG during bone remodeling in vivo to determine the relationship between osteoclastogenic stimulation and osteoblastic differentiation.
Total RNA was prepared from rat femurs after marrow ablation on days 0, 3, 6, and 9. The temporal activation patterns of osteoblast-related genes (procollagen alpha 1 (I), alkaline phosphatase, osteopontin, and osteocalcin) were examined by Northern blot analysis. An appreciable increase in the expression of these osteoblast markers was observed on day 3. The peak increase in gene expression was observed on day 6 followed by a slight reduction by day 9. Real-time PCR analysis showed that the OPG mRNA expression was markedly upregulated on day 6 and slightly decreased on day 9. In contrast, RANKL mRNA expression was increased by more than 20-fold on day 9. The RANKL/OPG ratio, an index of osteoclastogenic stimulation, peaked on day 9. Histological analysis showed that RANKL and OPG immunoreactivity were predominantly associated with bone marrow cells. The expression of bone formation markers was activated in the bone formation phase, followed by the stimulation of RANKL/OPG expression in the bone resorption phase, which confirmed that these molecules are key factors linking bone formation to resorption during bone remodeling. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Tanaka, H.] Yamaguchi Grand Med Ctr, Dept Orthoped Surg, Yamaguchi 7478511, Japan.
[Tanaka, H.; Ogasa, H.; Liang, C. T.] NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA.
[Mine, T.; Ogasa, H.; Taguchi, T.] Yamaguchi Univ Sch Med, Dept Orthoped Surg, Yamaguchi 7558505, Japan.
[Liang, C. T.] Natl Hlth Res Inst, Taipei 115, Taiwan.
RP Tanaka, H (reprint author), Yamaguchi Grand Med Ctr, Dept Orthoped Surg, 77 Ohsaki, Yamaguchi 7478511, Japan.
EM tnk@ymghp.jp
NR 22
TC 19
Z9 28
U1 0
U2 8
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD AUG 12
PY 2011
VL 411
IS 4
BP 690
EP 694
DI 10.1016/j.bbrc.2011.07.001
PG 5
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 812UB
UT WOS:000294317300007
PM 21771583
ER
PT J
AU Bae, GU
Domene, S
Roessler, E
Schachter, K
Kang, JS
Muenke, M
Krauss, RS
AF Bae, Gyu-Un
Domene, Sabina
Roessler, Erich
Schachter, Karen
Kang, Jong-Sun
Muenke, Maximilian
Krauss, Robert S.
TI Mutations in CDON, Encoding a Hedgehog Receptor, Result in
Holoprosencephaly and Defective Interactions with Other Hedgehog
Receptors
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID IG SUPERFAMILY MEMBER; SONIC HEDGEHOG; MYOGENIC DIFFERENTIATION;
BINDING; PROTEINS; PATHWAY; GAS1; BOC; MICE; ACTIVATION
AB Holoprosencephaly (HPE), a common human congenital anomaly defined by a failure to delineate the midline of the forebrain and/or midface, is associated with diminished Sonic hedgehog (SHH)-pathway activity in development of these structures. SHH signaling is regulated by a network of ligand-binding factors, including the primary receptor PTCH1 and the putative coreceptors, CDON (also called CDO), BOG, and GAS1. Although binding of SHH to these receptors promotes pathway activity, it is not known whether interactions between these receptors are important. We report here identification of missense CDON mutations in human HPE. These mutations diminish CDON's ability to support SHH-dependent gene expression in cell-based signaling assays. The mutations occur outside the SHH-binding domain of CDON, and the encoded variant CDON proteins do not display defects in binding to SHH. In contrast, wild-type CDON associates with PTCH1 and GAS1, but the variants do so inefficiently, in a manner that parallels their activity in cell-based assays. Our findings argue that CDON must associate with both ligand and other hedgehog-receptor components, particularly PTCH1, for signaling to occur and that disruption of the latter interactions is a mechanism of HPE.
C1 [Bae, Gyu-Un; Kang, Jong-Sun] Sungkyunkwan Univ, Sch Med, Samsung Biomed Res Inst, Dept Mol Cell Biol, Suwon 440746, South Korea.
[Bae, Gyu-Un; Schachter, Karen; Krauss, Robert S.] Mt Sinai Sch Med, Dept Dev & Regenerat Biol, New York, NY 10029 USA.
[Domene, Sabina; Roessler, Erich; Muenke, Maximilian] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Kang, JS (reprint author), Sungkyunkwan Univ, Sch Med, Samsung Biomed Res Inst, Dept Mol Cell Biol, Suwon 440746, South Korea.
EM kangj01@skku.edu; mamuenke@mail.nih.gov
FU March of Dimes; Ministry for Health, Welfare and Family Affairs,
Republic of Korea [A090176]; Korea government (MEST) [2011-0017315];
Division of Intramural Research, National Human Genome Research
Institute, National Institutes of Health, Department of Health and Human
Services
FX We are grateful to M. Lu for help with data analysis, B. Allen and F.
Charron for helpful discussions, R. Toftgard and A. McMahon for
reagents, and P. Wassarman and B. Gelb for critical reading of the
manuscript. This work was supported by a grant from the March of Dimes
(R.S.K.); by grants from the Korea Healthcare Technology R and D
Project, Ministry for Health, Welfare and Family Affairs, Republic of
Korea (A090176); and the National Research Foundation of Korea (NRF)
funded by the Korea government (MEST; 2011-0017315) (J.-S.K.); and by
the Division of Intramural Research, National Human Genome Research
Institute, National Institutes of Health, Department of Health and Human
Services (MM.).
NR 34
TC 55
Z9 57
U1 1
U2 10
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD AUG 12
PY 2011
VL 89
IS 2
BP 231
EP 240
DI 10.1016/j.ajhg.2011.07.001
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 810TA
UT WOS:000294148800003
PM 21802063
ER
PT J
AU Taymans, JM
Vancraenenbroeck, R
Ollikainen, P
Beilina, A
Lobbestael, E
De Maeyer, M
Baekelandt, V
Cookson, MR
AF Taymans, Jean-Marc
Vancraenenbroeck, Renee
Ollikainen, Petri
Beilina, Alexandra
Lobbestael, Evy
De Maeyer, Marc
Baekelandt, Veerle
Cookson, Mark R.
TI LRRK2 Kinase Activity Is Dependent on LRRK2 GTP Binding Capacity but
Independent of LRRK2 GTP Binding
SO PLOS ONE
LA English
DT Article
ID DISEASE-ASSOCIATED MUTATIONS; PARKINSONS-DISEASE; CYTOPLASMIC
LOCALIZATION; DOMINANT PARKINSONISM; NEURONAL TOXICITY; ROC DOMAIN;
PHOSPHORYLATES; PROTEIN; LEUCINE-RICH-REPEAT-KINASE-2; INHIBITION
AB Leucine rich repeat kinase 2 (LRRK2) is a Parkinson's disease (PD) gene that encodes a large multidomain protein including both a GTPase and a kinase domain. GTPases often regulate kinases within signal transduction cascades, where GTPases act as molecular switches cycling between a GTP bound "on'' state and a GDP bound "off'' state. It has been proposed that LRRK2 kinase activity may be increased upon GTP binding at the LRRK2 Ras of complex proteins (ROC) GTPase domain. Here we extensively test this hypothesis by measuring LRRK2 phosphorylation activity under influence of GDP, GTP or nonhydrolyzable GTP analogues GTP gamma S or GMPPCP. We show that autophosphorylation and lrrktide phosphorylation activity of recombinant LRRK2 protein is unaltered by guanine nucleotides, when co-incubated with LRRK2 during phosphorylation reactions. Also phosphorylation activity of LRRK2 is unchanged when the LRRK2 guanine nucleotide binding pocket is previously saturated with various nucleotides, in contrast to the greatly reduced activity measured for the guanine nucleotide binding site mutant T1348N. Interestingly, when nucleotides were incubated with cell lysates prior to purification of LRRK2, kinase activity was slightly enhanced by GTP gamma S or GMPPCP compared to GDP, pointing to an upstream guanine nucleotide binding protein that may activate LRRK2 in a GTP-dependent manner. Using metabolic labeling, we also found that cellular phosphorylation of LRRK2 was not significantly modulated by nucleotides, although labeling is significantly reduced by guanine nucleotide binding site mutants. We conclude that while kinase activity of LRRK2 requires an intact ROC-GTPase domain, it is independent of GDP or GTP binding to ROC.
C1 [Taymans, Jean-Marc; Ollikainen, Petri; Lobbestael, Evy; Baekelandt, Veerle] Katholieke Univ Leuven, Lab Neurobiol & Gene Therapy, Louvain, Belgium.
[Vancraenenbroeck, Renee; De Maeyer, Marc] Katholieke Univ Leuven, Lab Biomol Modeling, B-3001 Heverlee, Belgium.
[Beilina, Alexandra; Cookson, Mark R.] NIA, Cell Biol & Gene Express Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
RP Taymans, JM (reprint author), Katholieke Univ Leuven, Lab Neurobiol & Gene Therapy, Louvain, Belgium.
EM Jean-Marc.Taymans@med.kuleuven.be
OI Taymans, Jean-Marc/0000-0001-5503-5524
FU NIH, National Institute on Aging; Research Foundation-Flanders (FWO)
[G.0406.06, G.0666.09]; agency for Innovation by Science and Technology
[SBO 80020]; K.U.Leuven [OT/08/052A, IOF-KP/07/001]; Michael J. Fox
Foundation
FX This research was supported in part by the Intramural Research Program
of the NIH, National Institute on Aging. This work was supported by the
Research Foundation-Flanders (FWO Vlaanderen projects G.0406.06,
G.0666.09, postdoctoral fellowship to J-MT and doctoral fellowships to
RV and EL), the agency for Innovation by Science and Technology (IWT
project SBO 80020), the K.U.Leuven OT/08/052A and IOF-KP/07/001 and the
Michael J. Fox Foundation. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 37
TC 46
Z9 46
U1 3
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 12
PY 2011
VL 6
IS 8
AR e23207
DI 10.1371/journal.pone.0023207
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 808CT
UT WOS:000293953500024
PM 21858031
ER
PT J
AU Zare, H
Kaveh, M
Khodursky, A
AF Zare, Hossein
Kaveh, Mostafa
Khodursky, Arkady
TI Inferring a Transcriptional Regulatory Network from Gene Expression Data
Using Nonlinear Manifold Embedding
SO PLOS ONE
LA English
DT Article
ID DIMENSIONALITY REDUCTION; RECONSTRUCTION; MICROARRAY; FRAMEWORK
AB Transcriptional networks consist of multiple regulatory layers corresponding to the activity of global regulators, specialized repressors and activators as well as proteins and enzymes shaping the DNA template. Such intrinsic complexity makes uncovering connections difficult and it calls for corresponding methodologies, which are adapted to the available data. Here we present a new computational method that predicts interactions between transcription factors and target genes using compendia of microarray gene expression data and documented interactions between genes and transcription factors. The proposed method, called Kernel Embedding of Regulatory Networks (KEREN), is based on the concept of generegulon association, and captures hidden geometric patterns of the network via manifold embedding. We applied KEREN to reconstruct transcription regulatory interactions on a genome-wide scale in the model bacteria Escherichia coli (E. coli). Application of the method not only yielded accurate predictions of verifiable interactions, which outperformed on certain metrics comparable methodologies, but also demonstrated the utility of a geometric approach in the analysis of highdimensional biological data. We also described possible applications of kernel embedding techniques to other function and network discovery algorithms.
C1 [Zare, Hossein] NIH, Bethesda, MD 20892 USA.
[Kaveh, Mostafa] Univ Minnesota, Dept Elect & Comp Engn, Minneapolis, MN USA.
[Khodursky, Arkady] Univ Minnesota, Dept Biochem Biophys & Mol Biol, St Paul, MN 55108 USA.
RP Zare, H (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM khodu001@umn.edu
NR 26
TC 3
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 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 12
PY 2011
VL 6
IS 8
AR e21969
DI 10.1371/journal.pone.0021969
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 808CT
UT WOS:000293953500002
PM 21857910
ER
PT J
AU Calvo, E
Mizurini, DM
Sa-Nunes, A
Ribeiro, JMC
Andersen, JF
Mans, BJ
Monteiro, RQ
Kotsyfakis, M
Francischetti, IMB
AF Calvo, Eric
Mizurini, Daniella M.
Sa-Nunes, Anderson
Ribeiro, Jose M. C.
Andersen, John F.
Mans, Ben J.
Monteiro, Robson Q.
Kotsyfakis, Michail
Francischetti, Ivo M. B.
TI Alboserpin, a Factor Xa Inhibitor from the Mosquito Vector of Yellow
Fever, Binds Heparin and Membrane Phospholipids and Exhibits
Antithrombotic Activity
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PROTEIN-C INHIBITOR; VON-WILLEBRAND-FACTOR; IXODES-SCAPULARIS;
SALIVARY-GLAND; OXIDIZED PHOSPHOLIPIDS; PATHOGEN TRANSMISSION;
HEMATOPHAGOUS ANIMALS; ARTHROPOD SALIVA; HIGH-AFFINITY; TICK
AB The molecular mechanism of factor Xa (FXa) inhibition by Alboserpin, the major salivary gland anticoagulant from the mosquito and yellow fever vector Aedes albopictus, has been characterized. cDNA of Alboserpin predicts a 45-kDa protein that belongs to the serpin family of protease inhibitors. Recombinant Alboserpin displays stoichiometric, competitive, reversible and tight binding to FXa (picomolar range). Binding is highly specific and is not detectable for FX, catalytic site-blocked FXa, thrombin, and 12 other enzymes. Alboserpin displays high affinity binding to heparin (K-D similar to 20 nM), but no change in FXa inhibition was observed in the presence of the cofactor, implying that bridging mechanisms did not take place. Notably, Alboserpin was also found to interact with phosphatidylcholine and phosphatidylethanolamine but not with phosphatidylserine. Further, annexin V (in the absence of Ca2+) or heparin outcompetes Alboserpin for binding to phospholipid vesicles, suggesting a common binding site. Consistent with its activity, Alboserpin blocks prothrombinase activity and increases both prothrombin time and activated partial thromboplastin time in vitro or ex vivo. Furthermore, Alboserpin prevents thrombus formation provoked by ferric chloride injury of the carotid artery and increases bleeding in a dose-dependent manner. Alboserpin emerges as an atypical serpin that targets FXa and displays unique phospholipid specificity. It conceivably uses heparin and phosphatidylcholine/phosphatidylethanolamine as anchors to increase protein localization and effective concentration at sites of injury, cell activation, or inflammation.
C1 [Calvo, Eric; Sa-Nunes, Anderson; Ribeiro, Jose M. C.; Andersen, John F.; Mans, Ben J.; Kotsyfakis, Michail; Francischetti, Ivo M. B.] NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, Bethesda, MD 20852 USA.
[Mizurini, Daniella M.; Monteiro, Robson Q.] Univ Fed Rio de Janeiro, Inst Bioquim Med, BR-21941 Rio De Janeiro, Brazil.
[Sa-Nunes, Anderson] Univ Sao Paulo, Expt Immunol Lab, Dept Immunol, Inst Biomed Sci, BR-05508 Sao Paulo, Brazil.
[Mans, Ben J.] Onderstepoort Vet Inst, Agr Res Council, ZA-0110 Onderstepoort, South Africa.
[Kotsyfakis, Michail] Acad Sci Czech Republic, Inst Parasitol, Ctr Biol, Lab Genom & Prote Dis Vectors, Ceske Budejovice 37009, Czech Republic.
RP Francischetti, IMB (reprint author), NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Rm 2E-28, Bethesda, MD 20852 USA.
EM ifrancischetti@niaid.nih.gov
RI Sa-Nunes, Anderson/D-8667-2012; Inbeb, Inct/K-2317-2013; Kotsyfakis,
Michail/G-9525-2014; Monteiro, Robson/B-8007-2014;
OI Sa-Nunes, Anderson/0000-0002-1859-4973; Kotsyfakis,
Michail/0000-0002-7526-1876; Mans, Ben/0000-0002-0177-0029; Calvo,
Eric/0000-0001-7880-2730; Ribeiro, Jose/0000-0002-9107-0818
FU Division of Intramural Research, NIAID, National Institutes of Health
FX This work was supported, in whole or in part, by the Intramural Research
Program of the Division of Intramural Research, NIAID, National
Institutes of Health.
NR 60
TC 13
Z9 13
U1 0
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 12
PY 2011
VL 286
IS 32
BP 27998
EP 28010
DI 10.1074/jbc.M111.247924
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 803CJ
UT WOS:000293557800018
PM 21673107
ER
PT J
AU Yap, TL
Gruschus, JM
Velayati, A
Westbroek, W
Goldin, E
Moaven, N
Sidransky, E
Lee, JC
AF Yap, Thai Leong
Gruschus, James M.
Velayati, Arash
Westbroek, Wendy
Goldin, Ehud
Moaven, Nima
Sidransky, Ellen
Lee, Jennifer C.
TI alpha-Synuclein Interacts with Glucocerebrosidase Providing a Molecular
Link between Parkinson and Gaucher Diseases
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ACID-BETA-GLUCOSIDASE; LEWY BODY DISORDERS; HUMAN SAPOSIN-C;
X-RAY-STRUCTURE; FIBRIL FORMATION; LIPID RAFT; IN-VITRO; MUTATIONS;
PROTEIN; GENE
AB The presynaptic protein alpha-synuclein (alpha-syn), particularly in its amyloid form, is widely recognized for its involvement in Parkinson disease (PD). Recent genetic studies reveal that mutations in the gene GBA are the most widespread genetic risk factor for parkinsonism identified to date. GBA encodes for glucocerebrosidase (GCase), the enzyme deficient in the lysosomal storage disorder, Gaucher disease (GD). In this work, we investigated the possibility of a physical linkage between alpha-syn and GCase, examining both wild type and the GD-related N370S mutant enzyme. Using fluorescence and nuclear magnetic resonance spectroscopy, we determined that alpha-syn and GCase interact selectively under lysosomal solution conditions (pH 5.5) and mapped the interaction site to the alpha-syn C-terminal residues, 118-137. This alpha-syn-GCase complex does not form at pH 7.4 and is stabilized by electrostatics, with dissociation constants ranging from 1.2 to 22 mu M in the presence of 25 to 100mM NaCl. Intriguingly, the N370S mutant form of GCase has a reduced affinity for alpha-syn, as does the inhibitor conduritol-beta-epoxidebound enzyme. Immunoprecipitation and immunofluorescence studies verified this interaction in human tissue and neuronal cell culture, respectively. Although our data do not preclude protein-protein interactions in other cellular milieux, we suggest that the alpha-syn-GCase association is favored in the lysosome, and that this noncovalent interaction provides the groundwork to explore molecular mechanisms linking PD with mutant GBA alleles.
C1 [Yap, Thai Leong; Gruschus, James M.; Lee, Jennifer C.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
[Velayati, Arash; Westbroek, Wendy; Goldin, Ehud; Moaven, Nima; Sidransky, Ellen] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Sidransky, E (reprint author), 35 Convent Dr,Room 1A213, Bethesda, MD 20892 USA.
EM sidranse@mail.nih.gov; leej4@mail.nih.gov
RI Lee, Jennifer/E-9658-2015
OI Lee, Jennifer/0000-0003-0506-8349
FU National Institutes of Health; NHLBI; NHGRI
FX This work was supported by the Intramural Research Program at the
National Institutes of Health, NHLBI and NHGRI.
NR 77
TC 65
Z9 67
U1 1
U2 25
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 12
PY 2011
VL 286
IS 32
BP 28080
EP 28088
DI 10.1074/jbc.M111.237859
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 803CJ
UT WOS:000293557800026
PM 21653695
ER
PT J
AU Kautzmann, MAI
Kim, DS
Felder-Schmittbuhl, MP
Swaroop, A
AF Kautzmann, Marie-Audrey I.
Kim, Douglas S.
Felder-Schmittbuhl, Marie-Paule
Swaroop, Anand
TI Combinatorial Regulation of Photoreceptor Differentiation Factor, Neural
Retina Leucine Zipper Gene Nrl, Revealed by in Vivo Promoter Analysis
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID NUCLEAR RECEPTOR NR2E3; TRANSCRIPTION FACTOR NRL; LEBERS CONGENITAL
AMAUROSIS; CELL-FATE; CONE PHOTORECEPTORS; ROD PHOTORECEPTORS;
PINEAL-GLAND; EXPRESSION; DEGENERATION; BETA
AB Development and homeostasis require stringent spatiotemporal control of gene expression patterns that are established, to a large extent, by combinatorial action of transcription regulatory proteins. The bZIP transcription factor NRL (neural retina leucine zipper) is critical for rod versus cone photoreceptor cell fate choice during retinal development and acts as a molecular switch to produce rods from postmitotic precursors. Loss of Nrl in mouse leads to a cone-only retina, whereas ectopic expression of Nrl in photoreceptor precursors generates rods. To decipher the transcriptional regulatory mechanisms upstream of Nrl, we identified putative cis-control elements in the Nrl promoter/enhancer region by examining cross-species sequence conservation. Using in vivo transfection of promoter-reporter constructs into the mouse retina, we show that a 0.9-kb sequence upstream of the Nrl transcription initiation site is sufficient to drive reporter gene expression in photoreceptors. We further define a 0.3-kb sequence including a proximal promoter (cluster A1) and an enhancer (cluster B) that can direct rod-specific expression in vivo. Electrophoretic mobility shift assays using mouse retinal nuclear extracts, in combination with specific antibodies, demonstrate the binding of retinoid-related orphan nuclear receptor beta (ROR beta), cone rod homeobox, orthodenticle homolog 2, and cyclic AMP response element-binding protein to predicted consensus elements within clusters A and B. Our studies demonstrate Nrl as a direct transcriptional target of ROR beta and suggest that combinatorial action of multiple regulatory factors modulates the expression of Nrl in developing and mature retina.
C1 [Kautzmann, Marie-Audrey I.; Kim, Douglas S.; Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
[Felder-Schmittbuhl, Marie-Paule] CNRS, UPR 3212, Inst Neurosci Cellulaires & Integrat, Dept Neurobiol Rythmes, F-67084 Strasbourg, France.
RP Swaroop, A (reprint author), NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bldg 6-338,6 Ctr Dr,MSC0610, Bethesda, MD 20892 USA.
EM swaroopa@nei.nih.gov
OI Swaroop, Anand/0000-0002-1975-1141
FU NEI, National Institutes of Health
FX This work was supported by the intramural program of NEI, National
Institutes of Health.
NR 66
TC 15
Z9 16
U1 0
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 12
PY 2011
VL 286
IS 32
BP 28247
EP 28255
DI 10.1074/jbc.M111.257246
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 803CJ
UT WOS:000293557800042
PM 21673114
ER
PT J
AU Bryksa, BC
Bhaumik, P
Magracheva, E
De Moura, DC
Kurylowicz, M
Zdanov, A
Dutcher, JR
Wlodawer, A
Yada, RY
AF Bryksa, Brian C.
Bhaumik, Prasenjit
Magracheva, Eugenia
De Moura, Dref C.
Kurylowicz, Martin
Zdanov, Alexander
Dutcher, John R.
Wlodawer, Alexander
Yada, Rickey Y.
TI Structure and Mechanism of the Saposin-like Domain of a Plant Aspartic
Protease
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HEMAGGLUTININ FUSION PEPTIDE; INFLUENZA HEMAGGLUTININ; MEMBRANE-FUSION;
CRYSTAL-STRUCTURE; ANTIMICROBIAL ACTIVITY; SECONDARY-STRUCTURE;
MAXIMUM-LIKELIHOOD; LIPID-BILAYERS; PROTEINASE; CELL
AB Many plant aspartic proteases contain an additional sequence of similar to 100 amino acids termed the plant-specific insert, which is involved in host defense and vacuolar targeting. Similar to all saposin-like proteins, the plant-specific insert functions via protein-membrane interactions; however, the structural basis for such interactions has not been studied, and the nature of plantspecific insert-mediated membrane disruption has not been characterized. In the present study, the crystal structure of the saposin-like domain of potato aspartic protease was resolved at a resolution of 1.9 angstrom, revealing an open V-shaped configuration similar to the open structure of human saposin C. Notably, vesicle disruption activity followed Michaelis-Menten-like kinetics, a finding not previously reported for saposin-like proteins including plant-specific inserts. Circular dichroism data suggested that secondary structure was pH-dependent in a fashion similar to influenza A hemagglutinin fusion peptide. Membrane effects characterized by atomic force microscopy and light scattering indicated bilayer solubilization as well as fusogenic activity. Taken together, the present study is the first report to elucidate the membrane interaction mechanism of plant saposin-like domains whereby pH-dependent membrane interactions resulted in bilayer fusogenic activity that probably arose from a viral type pH-dependent helix-kink-helix motif at the plant-specific insert N terminus.
C1 [Bryksa, Brian C.; De Moura, Dref C.; Yada, Rickey Y.] Univ Guelph, Dept Food Sci, Guelph, ON N1G 2W1, Canada.
[Kurylowicz, Martin; Dutcher, John R.] Univ Guelph, Dept Phys, Guelph, ON N1G 2W1, Canada.
[Bhaumik, Prasenjit; Zdanov, Alexander; Wlodawer, Alexander] NCI, Prot Struct Sect, Macromol Crystallog Lab, NIH, Frederick, MD 21702 USA.
[Magracheva, Eugenia] NCI, Basic Res Program, SAIC Frederick, NIH, Frederick, MD 21702 USA.
RP Yada, RY (reprint author), Univ Guelph, Dept Food Sci, Guelph, ON N1G 2W1, Canada.
EM ryada@uoguelph.ca
RI Yada, Rickey/A-8289-2013; Bryksa, Brian/A-8281-2013
OI Bryksa, Brian/0000-0001-5626-8012
FU National Institutes of Health, NCI; Natural Sciences and Engineering
Research Council of Canada; Canada Research Chairs Program; Center for
Cancer Research
FX This work was supported, in whole or in part, by the Intramural Research
Program of the National Institutes of Health, NCI. This work was also
supported by the Natural Sciences and Engineering Research Council of
Canada, the Canada Research Chairs Program, and the Center for Cancer
Research.
NR 85
TC 17
Z9 19
U1 1
U2 6
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 12
PY 2011
VL 286
IS 32
BP 28265
EP 28275
DI 10.1074/jbc.M111.252619
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 803CJ
UT WOS:000293557800044
PM 21676875
ER
PT J
AU Murga-Zamalloa, CA
Ghosh, AK
Patil, SB
Reed, NA
Chan, LS
Davuluri, S
Peranen, J
Hurd, TW
Rachel, RA
Khanna, H
AF Murga-Zamalloa, Carlos A.
Ghosh, Amiya K.
Patil, Suresh B.
Reed, Nathan A.
Chan, Lan Sze
Davuluri, Supriya
Peranen, Johan
Hurd, Toby W.
Rachel, Rivka A.
Khanna, Hemant
TI Accumulation of the Raf-1 Kinase Inhibitory Protein (Rkip) Is Associated
with Cep290-mediated Photoreceptor Degeneration in Ciliopathies
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID DOMINANT RETINITIS-PIGMENTOSA; BARDET-BIEDL-SYNDROME; RETINAL
DEGENERATION; VERTEBRATE PHOTORECEPTOR; INTRAFLAGELLAR TRANSPORT; OUTER
SEGMENTS; PRIMARY CILIA; CENTROSOMAL PROTEIN; JOUBERT-SYNDROME; SENSORY
CILIUM
AB Primary cilia regulate polarized protein trafficking in photo-receptors, which are dynamic and highly compartmentalized sensory neurons of retina. The ciliary protein Cep290 modulates cilia formation and is frequently mutated in syndromic and non-syndromic photoreceptor degeneration. However, the underlying mechanism of associated retinopathy is unclear. Using the Cep290 mutant mouse rd16 (retinal degeneration 16), we show that Cep290-mediated photoreceptor degeneration is associated with aberrant accumulation of its novel interacting partner Rkip (Raf-1 kinase inhibitory protein). This effect is phenocopied by morpholino-mediated depletion of cep290 in zebrafish. We further demonstrate that ectopic accumulation of Rkip leads to defective cilia formation in zebrafish and cultured cells, an effect mediated by its interaction with the ciliary GTPase Rab8A. Our data suggest that Rkip prevents cilia formation and is associated with Cep290-mediated photoreceptor degeneration. Furthermore, our results indicate that preventing accumulation of Rkip could potentially ameliorate such degeneration.
C1 [Murga-Zamalloa, Carlos A.; Ghosh, Amiya K.; Patil, Suresh B.; Reed, Nathan A.; Chan, Lan Sze; Davuluri, Supriya; Khanna, Hemant] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA.
[Hurd, Toby W.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48105 USA.
[Patil, Suresh B.; Davuluri, Supriya; Khanna, Hemant] Univ Massachusetts, Sch Med, Dept Ophthalmol, Worcester, MA 01605 USA.
[Peranen, Johan] Univ Helsinki, Inst Biotechnol, FIN-00014 Helsinki, Finland.
[Rachel, Rivka A.] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
RP Khanna, H (reprint author), 381 Plantat St,Biotech 5,Suite 250, Worcester, MA 01605 USA.
EM hemant.khanna@umassmed.edu
FU National Institutes of Health [EY007961, 5P60 DK20572]; Michigan
Diabetes Research and Training Center; Foundation for Fighting
Blindness; Midwest Eye Banks and Transplantation Center; Vision Core
Facilities [EY07003]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants EY007961 and 5P60 DK20572 to the Michigan Diabetes
Research and Training Center, the Foundation for Fighting Blindness, and
Midwest Eye Banks and Transplantation Center, and Vision Core Facilities
Grant EY07003.
NR 60
TC 21
Z9 21
U1 0
U2 0
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 12
PY 2011
VL 286
IS 32
BP 28276
EP 28286
DI 10.1074/jbc.M111.237560
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 803CJ
UT WOS:000293557800045
PM 21685394
ER
PT J
AU McMillin, SM
Heusel, M
Liu, T
Costanzi, S
Wess, J
AF McMillin, Sara M.
Heusel, Moritz
Liu, Tong
Costanzi, Stefano
Wess, Juergen
TI Structural Basis of M-3 Muscarinic Receptor Dimer/Oligomer Formation
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PROTEIN-COUPLED RECEPTOR; RESONANCE ENERGY-TRANSFER;
ACETYLCHOLINE-RECEPTORS; QUANTITATIVE-ANALYSIS; INTERNATIONAL UNION;
SECRETIN RECEPTOR; REVEALS OLIGOMERS; HORMONE RECEPTOR; MOLECULAR-BASIS;
DRUG DISCOVERY
AB Class A G protein-coupled receptors (GPCRs) are known to form dimers and/or oligomeric arrays in vitro and in vivo. These complexes are thought to play important roles in modulating class A GPCR function. Many studies suggest that residues located on the "outer" (lipid-facing) surface of the transmembrane (TM) receptor core are critically involved in the formation of class A receptor dimers (oligomers). However, no clear consensus has emerged regarding the identity of the TM helices or TM subsegments involved in this process. To shed light on this issue, we have used the M-3 muscarinic acetylcholine receptor (M3R), a prototypic class A GPCR, as a model system. Using a comprehensive and unbiased approach, we subjected all outward-facing residues (70 amino acids total) of the TM helical bundle (TM1-7) of the M3R to systematic alanine substitution mutagenesis. We then characterized the resulting mutant receptors in radioligand binding and functional studies and determined their ability to form dimers (oligomers) in bioluminescence resonance energy transfer saturation assays. We found that M3R/M3R interactions are not dependent on the presence of one specific structural motif but involve the outer surfaces of multiple TM subsegments (TM1-5 and -7) located within the central and endofacial portions of the TM receptor core. Moreover, we demonstrated that the outward-facing surfaces of most TM helices play critical roles in proper receptor folding and/or function. Guided by the bioluminescence resonance energy transfer data, molecular modeling studies suggested the existence of multiple dimeric/oligomeric M3R arrangements, which may exist in a dynamic equilibrium. Given the high structural homology found among all class A GPCRs, our results should be of considerable general relevance.
C1 [Wess, Juergen] NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Costanzi, Stefano] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
RP Wess, J (reprint author), NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bldg 8A,Rm B1A-05,8 Ctr Dr,MSC 0810, Bethesda, MD 20892 USA.
EM jwess@helix.nih.gov
RI Costanzi, Stefano/G-8990-2013;
OI Costanzi, Stefano/0000-0003-3183-7332
FU National Institutes of Health, NIDDK
FX This work was supported, in whole or in part, by National Institutes of
Health Intramural Research Program, NIDDK.
NR 71
TC 32
Z9 32
U1 0
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 12
PY 2011
VL 286
IS 32
BP 28584
EP 28598
DI 10.1074/jbc.M111.259788
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 803CJ
UT WOS:000293557800073
PM 21685385
ER
PT J
AU Driscoll, CA
Luo, SJ
Macdonald, D
Dinerstein, E
Chestin, I
Pereladova, O
O'Brien, SJ
AF Driscoll, Carlos A.
Luo, Shujin
Macdonald, David
Dinerstein, Eric
Chestin, Igor
Pereladova, Olga
O'Brien, Stephen J.
TI Restoring Tigers to the Caspian Region
SO SCIENCE
LA English
DT Letter
C1 [Driscoll, Carlos A.; O'Brien, Stephen J.] NCI, Lab Genom Divers, Frederick, MD 21702 USA.
[Driscoll, Carlos A.; Macdonald, David] Univ Oxford, Dept Zool, Wildlife Conservat Res Unit, Tubney OX13 5QL, Oxon, England.
[Luo, Shujin] Peking Univ, Sch Life Sci, Beijing 100871, Peoples R China.
[Dinerstein, Eric] World Wildlife Fund WWF US, Conservat Sci Program, Washington, DC 20037 USA.
[Chestin, Igor; Pereladova, Olga] WWF Russia, Cent Asia Programme, Moscow 109240, Russia.
RP O'Brien, SJ (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA.
EM stephen.obrien@nih.gov
OI Driscoll, Carlos/0000-0003-2392-505X
NR 9
TC 3
Z9 4
U1 4
U2 33
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD AUG 12
PY 2011
VL 333
IS 6044
BP 822
EP 823
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 806DJ
UT WOS:000293785400016
PM 21835996
ER
PT J
AU Huang, XM
Auinger, P
Eberly, S
Oakes, D
Schwarzschild, M
Ascherio, A
Mailman, R
Chen, HL
AF Huang, Xuemei
Auinger, Peggy
Eberly, Shirley
Oakes, David
Schwarzschild, Michael
Ascherio, Alberto
Mailman, Richard
Chen, Honglei
CA Parkinson Study Grp DATATOP
TI Serum Cholesterol and the Progression of Parkinson's Disease: Results
from DATATOP
SO PLOS ONE
LA English
DT Article
ID DENSITY-LIPOPROTEIN CHOLESTEROL; INCREASES DOPAMINE RELEASE; RAT
NUCLEUS-ACCUMBENS; IN-VITRO; RISK; STATINS; COHORT; DISABILITY; MORPHINE
AB Background: Recent studies have suggested that higher serum cholesterol may be associated with lower occurrence of Parkinson's disease (PD). This study is to test the hypothesis that higher serum cholesterol correlates with slower PD progression.
Methods: Baseline non-fasting serum total cholesterol was measured in 774 of the 800 subjects with early PD enrolled between 1987 and 1988 in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) trial. Participants were followed for up to two years, with clinical disability requiring levodopa therapy as the primary endpoint. Hazard ratios (HRs) and 95% confidence intervals (CI) were determined for increasing serum cholesterol concentration (in quintiles) for clinical disability requiring levodopa therapy, after adjusting for confounders. At baseline, only nine subjects reported use of cholesterol-lowering agents (two with statins).
Results: The overall mean cholesterol level was 216 mg/dL (range 100-355). The HR of progressing to the primary endpoint decreased with increasing serum cholesterol concentrations. Compared to the lowest quintile, the HRs (95% CI), for each higher quintile (in ascending order) are 0.83 (0.59-1.16); 0.86 (0.61-1.20); 0.84 (0.60-1.18); and 0.75 (0.52-1.09). The HR for one standard deviation (SD) increase = 0.90 [(0.80-1.01), p for trend = 0.09]. This trend was found in males (HR per SD = 0.88 [(0.77-1.00), p for trend = 0.05], but not in females [ HR = 1.03 (0.81-1.32)].
Conclusions: This secondary analysis of the DATATOP trial provides preliminary evidence that higher total serum cholesterol concentrations may be associated with a modest slower clinical progression of PD, and this preliminary finding needs confirmation from larger prospective studies.
C1 [Huang, Xuemei; Mailman, Richard] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurol, Hershey, PA 17033 USA.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurosurg, Hershey, PA 17033 USA.
[Huang, Xuemei; Mailman, Richard] Penn State Univ, Milton S Hershey Med Ctr, Dept Pharmacol, Hershey, PA 17033 USA.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Radiol, Hershey, PA 17033 USA.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Kinesiol, Hershey, PA 17033 USA.
[Auinger, Peggy] Univ Rochester, Sch Med & Dent, Dept Neurol, Ctr Human Expt Therapeut, Rochester, NY 14642 USA.
[Eberly, Shirley; Oakes, David] Univ Rochester, Sch Med & Dent, Dept Biostat, Rochester, NY USA.
[Schwarzschild, Michael] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Chen, Honglei] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA.
RP Huang, XM (reprint author), Penn State Univ, Milton S Hershey Med Ctr, Dept Neurol, Hershey, PA 17033 USA.
EM Xuemei@psu.edu
OI Mailman, Richard/0000-0003-1353-2738; Chen, Honglei/0000-0003-3446-7779
FU Parkinson's Disease Foundation; National Institutes of Health
[NS060722]; Pennsylvania Tobacco Settlement Fund; National Institute of
Environmental Health Sciences [Z01-ES-101986]
FX This work was supported, in part, by Parkinson's Disease Foundation,
National Institutes of Health (NS060722 to XH), the Pennsylvania Tobacco
Settlement Fund, and the intramural research program of the National
Institute of Environmental Health Sciences (Z01-ES-101986 to HC). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation.
NR 34
TC 16
Z9 16
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 11
PY 2011
VL 6
IS 8
AR e22854
DI 10.1371/journal.pone.0022854
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 808CS
UT WOS:000293953400015
PM 21853051
ER
PT J
AU Pham, CD
Sims, HI
Archer, TK
Schnitzler, GR
AF Pham, Chuong D.
Sims, Hillel I.
Archer, Trevor K.
Schnitzler, Gavin R.
TI Multiple Distinct Stimuli Increase Measured Nucleosome Occupancy around
Human Promoters
SO PLOS ONE
LA English
DT Article
ID TUMOR VIRUS PROMOTER; CHROMATIN REMODELING COMPLEXES; MEDIATES CRITICAL
INTERACTIONS; SWI/SNF-RELATED COMPLEXES; LONG TERMINAL REPEAT;
CELL-CYCLE CONTROL; C-MYC GENE; GLUCOCORTICOID-RECEPTOR; IN-VIVO;
NUCLEAR RECEPTORS
AB Nucleosomes can block access to transcription factors. Thus the precise localization of nucleosomes relative to transcription start sites and other factor binding sites is expected to be a critical component of transcriptional regulation. Recently developed microarray approaches have allowed the rapid mapping of nucleosome positions over hundreds of kilobases (kb) of human genomic DNA, although these approaches have not yet been widely used to measure chromatin changes associated with changes in transcription. Here, we use custom tiling microarrays to reveal changes in nucleosome positions and abundance that occur when hormone-bound glucocorticoid receptor (GR) binds to sites near target gene promoters in human osteosarcoma cells. The most striking change is an increase in measured nucleosome occupancy at sites spanning similar to 1 kb upstream and downstream of transcription start sites, which occurs one hour after addition of hormone, but is lost at 4 hours. Unexpectedly, this increase was seen both on GR-regulated and GR-non-regulated genes. In addition, the human SWI/SNF chromatin remodeling factor (a GR co-activator) was found to be important for increased occupancy upon hormone treatment and also for low nucleosome occupancy without hormone. Most surprisingly, similar increases in nucleosome occupancy were also seen on both regulated and non-regulated promoters during differentiation of human myeloid leukemia cells and upon activation of human CD4+ T-cells. These results indicate that dramatic changes in chromatin structure over similar to 2 kb of human promoters may occur genomewide and in response to a variety of stimuli, and suggest novel models for transcriptional regulation.
C1 [Pham, Chuong D.] AstraZeneca R&D Boston, Waltham, MA 02451 USA.
[Sims, Hillel I.] Brandeis Univ, Dept Biol, Rosenstiel Basic Med Sci Res Ctr, Waltham, MA 02254 USA.
[Archer, Trevor K.] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Schnitzler, Gavin R.] Tufts Med Ctr, Mol Cardiol Res Inst, Boston, MA USA.
RP Pham, CD (reprint author), AstraZeneca R&D Boston, Waltham, MA 02451 USA.
EM gschnitzler@tuftsmedicalcenter.org
FU American Cancer Society [RSG-04-188-01-GMC]
FX This work was supported by a grant to GRS from the American Cancer
Society (#RSG-04-188-01-GMC, www.cancer.org). The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 78
TC 3
Z9 3
U1 1
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 11
PY 2011
VL 6
IS 8
AR e23490
DI 10.1371/journal.pone.0023490
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 808CS
UT WOS:000293953400047
PM 21853138
ER
PT J
AU Tjomsland, V
Ellegard, R
Che, K
Hinkula, J
Lifson, JD
Larsson, M
AF Tjomsland, Veronica
Ellegard, Rada
Che, Karlhans
Hinkula, Jorma
Lifson, Jeffrey D.
Larsson, Marie
TI Complement Opsonization of HIV-1 Enhances the Uptake by Dendritic Cells
and Involves the Endocytic Lectin and Integrin Receptor Families
SO PLOS ONE
LA English
DT Article
ID CD4 T-CELLS; DC-SIGN; APOPTOTIC CELLS; INFECTION; ADHESION; VIRUS;
ANTIBODY; MEDIATE; CR3; VISUALIZATION
AB Interaction with the complement system is an underappreciated aspect of HIV-1 infection; even in primary infection, complement fragments are found on virions with potential to affect the interplay between the virus and dendritic cells (DC). Since opsonization may affect the efficiency of uptake and the type of receptors utilized, we compared the interactions of DC with free HIV-1 (F-HIV) and complement opsonized HIV-1 (C-HIV). We demonstrate that C-HIV significantly enhanced the uptake by immature DC (IDC) and mature DC (MDC) and that the internalization rate was dependent on both opsonization of the virus and DC maturation state. Increased DC uptake of C-HIV was not due to opsonization related increased binding of virus to the surface of DC but rather increased internalization of C-HIV despite utilizing a similar repertoire of receptors as F-HIV. Both F-HIV and C-HIV interacted with C-type lectins, integrins, and CD4 and blocking these receptor families prevented HIV-1 from binding to DC at 4 degrees C. Blocking integrins significantly reduced the binding and uptake of F-HIV and C-HIV implicating the involvement of several integrins such as beta 1-integrin, CR3, LFA-1, and alpha 4 beta 7. Distinctive for C-HIV was usage of beta 1-integrin and for F-HIV, usage of beta 7-integrin, whereas both F-HIV and C-HIV utilized both integrin chains of CR3. We have in this study identified the receptor types used by both F-HIV and C-HIV to bind to DC. Noteworthy, C-HIV was internalized more efficiently by DC than F-HIV, probably via receptor mediated endocytosis, which may entail different intracellular processing of the virus leading to both elevated infection and altered activation of HIV specific immune responses.
C1 [Tjomsland, Veronica; Ellegard, Rada; Che, Karlhans; Hinkula, Jorma; Larsson, Marie] Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.
[Lifson, Jeffrey D.] NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
RP Tjomsland, V (reprint author), Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.
EM marie.larsson@liu.se
OI Hinkula, Jorma/0000-0003-1908-5609
FU Swedish Research Council [ML: AI52731]; Swedish, Physicians against AIDS
Research Foundation; Swedish International Development Cooperation
Agency; SIDA SARC; VINNMER for Vinnova; Linkoping University Hospital; C
ALF; Swedish Society of Medicine; National Cancer Institute, National
Institutes of Health [HHSN261200800001E]
FX This work has been supported by grants through: ML: AI52731, The Swedish
Research Council, The Swedish, Physicians against AIDS Research
Foundation, The Swedish International Development Cooperation Agency;
SIDA SARC, VINNMER for Vinnova, Linkoping University Hospital Research
Fund, C ALF, and The Swedish Society of Medicine; also in part with
federal funds from the National Cancer Institute, National Institutes of
Health, under contract HHSN261200800001E (JDL). The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 40
TC 10
Z9 10
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 11
PY 2011
VL 6
IS 8
AR e23542
DI 10.1371/journal.pone.0023542
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 808CS
UT WOS:000293953400051
PM 21853149
ER
PT J
AU Demberg, T
Ettinger, AC
Aladi, S
McKinnon, K
Kuddo, T
Venzon, D
Patterson, LJ
Phillips, TM
Robert-Guroff, M
AF Demberg, Thorsten
Ettinger, Amelia C.
Aladi, Stanley
McKinnon, Katherine
Kuddo, Thea
Venzon, David
Patterson, L. Jean
Phillips, Terry M.
Robert-Guroff, Marjorie
TI Strong viremia control in vaccinated macaques does not prevent gradual
Th17 cell loss from central memory
SO VACCINE
LA English
DT Article
DE Th17 cells; Tc17 cells; Simian/human immunodeficiency virus; Chronic
immune activation; Microbial translocation; Vaccine
ID SIMIAN IMMUNODEFICIENCY VIRUS; CD4(+) T-CELLS; HELPER 17 CELLS;
TRANSLATIONAL MINIREVIEW SERIES; PLASMACYTOID DENDRITIC CELLS; HIV-1
DISEASE PROGRESSION; ACUTE SIV INFECTION; MICROBIAL TRANSLOCATION;
IMMUNE ACTIVATION; RHESUS MACAQUES
AB It has been proposed that microbial translocation might play a role in chronic immune activation during HIV/SIV infection. Key roles in fighting bacterial and fungal infections have been attributed to Th17 and Tc17 cells. Th17 cells can be infected with HIV/SIV, however whether effective vaccination leads to their maintenance following viral challenge has not been addressed. Here we retrospectively investigated if a vaccine regimen that potently reduced viremia post-challenge preserved Th17 and Tc17 cells, thus adding benefit in the absence of sterilizing protection. Rhesus macaques were previously vaccinated with replication-competent Adenovirus recombinants expressing HIVtat and HIVenv followed by Tat and gp140 protein boosting. Upon SHIV(89.6P) challenge, the vaccines exhibited a significant 4 log reduction in chronic viremia compared to sham vaccinated controls which rapidly progressed to AIDS [39]. Plasma and cryopreserved PBMC samples were examined pre-challenge and during acute and chronic infection. Control macaques exhibited a rapid loss of CD4(+) cells, including Th17 cells. Tc17 cells tended to decline over the course of infection although significance was not reached. Immune activation, assessed by Ki-67 expression, was associated with elevated chronic viremia of the controls. Significantly increased plasma IFN-gamma levels were also observed. No increase in plasma LPS levels were observed suggesting a lack of microbial translocation. In contrast, vaccinated macaques had no evidence of immune activation within the chronic phase and preserved both CD4(+) T-cells and Tc17 cells in PBMC. Nevertheless, they exhibited a gradual, significant loss of Th17 cells which concomitantly displayed significantly higher CCR6 expression over time. The gradual Th17 cell decline may reflect mucosal homing to inflammatory sites and/or slow depletion due to ongoing low levels of SHIV replication. Our results suggest that potent viremia reduction during chronic SHIV infection will delay but not prevent the loss of Th17 cells. Published by Elsevier Ltd.
C1 [Robert-Guroff, Marjorie] NCI, NIH, Vaccine Branch, Bethesda, MD 20892 USA.
[Kuddo, Thea; Phillips, Terry M.] Natl Inst Biomed Imaging & Bioengn, Lab Cellular Imaging & Macromol Biophys, Bethesda, MD 20892 USA.
[Venzon, David] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA.
RP Robert-Guroff, M (reprint author), NCI, NIH, Vaccine Branch, 41 Medlars Dr,Bldg 41,Room D804, Bethesda, MD 20892 USA.
EM guroffm@mail.nih.gov
FU National Institutes of Health, National Cancer Institute
FX We thank Dr. Claudio Fenizia for providing the MxA primer sequences.
This work was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute.
NR 86
TC 7
Z9 7
U1 0
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD AUG 11
PY 2011
VL 29
IS 35
BP 6017
EP 6028
DI 10.1016/j.vaccine.2011.06.032
PG 12
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 810RX
UT WOS:000294145900025
PM 21708207
ER
PT J
AU Landgren, O
AF Landgren, Ola
TI Sun, mother of life, prevents cancer
SO BLOOD
LA English
DT Editorial Material
ID NON-HODGKIN-LYMPHOMA; RISK; EXPOSURE
AB In this issue of Blood, based on a large, prospective cohort study of 121 216 California women, Chang et al report on an inverse association between ultraviolet radiation exposure and a 40% to 50% reduced risk of developing non-Hodgkin lymphoma (NHL)-particularly diffuse large B-cell lymphoma (DLBCL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)-and multiple myeloma.(1)
C1 Natl Inst Hlth, Baltimore, MD USA.
RP Landgren, O (reprint author), Natl Inst Hlth, Baltimore, MD USA.
NR 8
TC 1
Z9 1
U1 0
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 11
PY 2011
VL 118
IS 6
BP 1431
EP 1432
DI 10.1182/blood-2011-06-359794
PG 4
WC Hematology
SC Hematology
GA 806DW
UT WOS:000293787300003
PM 21835960
ER
PT J
AU Andresen, V
Pise-Masison, CA
Sinha-Datta, U
Bellon, M
Valeri, V
Parks, RW
Cecchinato, V
Fukumoto, R
Nicot, C
Franchini, G
AF Andresen, Vibeke
Pise-Masison, Cynthia A.
Sinha-Datta, Uma
Bellon, Marcia
Valeri, Valerio
Parks, Robyn Washington
Cecchinato, Valentina
Fukumoto, Risaku
Nicot, Christophe
Franchini, Genoveffa
TI Suppression of HTLV-1 replication by Tax-mediated rerouting of the p13
viral protein to nuclear speckles
SO BLOOD
LA English
DT Article
ID T-CELL LEUKEMIA; VIRUS TYPE-I; NF-KAPPA-B; OPEN READING FRAMES;
LYMPHOTROPIC-VIRUS; TYPE-1 TAX; TRANSCRIPTION FACTOR; LYSINE RESIDUES;
P13(II) PROTEIN; DOWN-REGULATION
AB Disease development in human T-cell leukemia virus type 1 (HTLV-1)-infected individuals is positively correlated with the level of integrated viral DNA in T cells. HTLV-1 replication is positively regulated by Tax and Rex and negatively regulated by the p30 and HBZ proteins. In the present study, we demonstrate that HTLV-1 encodes another negative regulator of virus expression, the p13 protein. Expressed separately, p13 localizes to the mitochondria, whereas in the presence of Tax, part of it is ubiquitinated, stabilized, and rerouted to the nuclear speckles. The p13 protein directly binds Tax, decreases Tax binding to the CBP/p300 transcriptional coactivator, and, by reducing Tax transcriptional activity, suppresses viral expression. Because Tax stabilizes its own repressor, these findings suggest that HTLV-1 has evolved a complex mechanism to control its own replication. Further, these results highlight the importance of studying the function of the HTLV- 1 viral proteins, not only in isolation, but also in the context of full viral replication. (Blood. 2011;118(6):1549-1559)
C1 [Andresen, Vibeke; Pise-Masison, Cynthia A.; Valeri, Valerio; Parks, Robyn Washington; Cecchinato, Valentina; Fukumoto, Risaku; Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA.
[Sinha-Datta, Uma; Bellon, Marcia; Nicot, Christophe] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66103 USA.
RP Franchini, G (reprint author), NCI, Anim Models & Retroviral Vaccines Sect, Bldg 41,Rm D-804, Bethesda, MD 20892 USA.
EM franchig@mail.nih.gov
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health, Bethesda, MD
FX This research was supported by the Intramural Research Program of the
Center for Cancer Research, National Cancer Institute, National
Institutes of Health, Bethesda, MD.
NR 60
TC 19
Z9 19
U1 0
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 11
PY 2011
VL 118
IS 6
BP 1549
EP 1559
DI 10.1182/blood-2010-06-293340
PG 11
WC Hematology
SC Hematology
GA 806DW
UT WOS:000293787300022
PM 21677314
ER
PT J
AU Kenyon, V
Rai, G
Jadhav, A
Schultz, L
Armstrong, M
Jameson, JB
Perry, S
Joshi, N
Bougie, JM
Leister, W
Taylor-Fishwick, DA
Nadler, JL
Holinstat, M
Simeonov, A
Maloney, DJ
Holman, TR
AF Kenyon, Victor
Rai, Ganesha
Jadhav, Ajit
Schultz, Lena
Armstrong, Michelle
Jameson, J. Brian, II
Perry, Steven
Joshi, Netra
Bougie, James M.
Leister, William
Taylor-Fishwick, David A.
Nadler, Jerry L.
Holinstat, Michael
Simeonov, Anton
Maloney, David J.
Holman, Theodore R.
TI Discovery of Potent and Selective Inhibitors of Human Platelet-Type
12-Lipoxygenase
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID HUMAN LIPOXYGENASE INHIBITORS; SPONGE-DERIVED TERPENOIDS;
PROSTATE-CANCER CELLS; HUMAN BREAST-CANCER; 5-LIPOXYGENASE INHIBITORS;
ARACHIDONIC-ACID; SOYBEAN LIPOXYGENASE-1; 12-HUMAN LIPOXYGENASE;
BIOLOGICAL-ACTIVITIES; HUMAN 15-LIPOXYGENASE
AB We report the discovery of novel small molecule inhibitors of platelet-type 12-human lipoxygenase, which display nanomolar activity against the purified enzyme, using a quantitative high-throughput screen (qHTS) on a library of 153607 compounds. These compounds also exhibit excellent specificity, >50-fold selectivity vs the paralogues, 5-human lipoxygenase, reticulocyte 15-human lipoxygenase type-1, and epithelial 15-human lipoxygenase type-2, and >100-fold selectivity vs ovine cyclooxygenase-1 and human cyclooxygenase-2. Kinetic experiments indicate this chemotype is a noncompetitive inhibitor that does not reduce the active site iron. Moreover, chiral HPLC separation of two of the racemic lead molecules revealed a strong preference for the (-)-enantiomers (IC50 of 0.43 +/- 0.04 and 0.38 +/- 0.05 mu M) compared to the (+)-enantiomers (IC50 of >25 mu M for both), indicating a fine degree of selectivity in the active site due to chiral geometry. In addition, these compounds demonstrate efficacy in cellular models, which underscores their relevance to disease modification.
C1 [Rai, Ganesha; Jadhav, Ajit; Schultz, Lena; Bougie, James M.; Leister, William; Simeonov, Anton; Maloney, David J.] NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA.
[Taylor-Fishwick, David A.; Nadler, Jerry L.] Eastern Virginia Med Sch, Dept Internal Med, Strelitz Diabet Ctr, Norfolk, VA 23501 USA.
[Holinstat, Michael] Thomas Jefferson Univ, Dept Med, Cardeza Fdn Hematol Res, Philadelphia, PA 19107 USA.
[Kenyon, Victor; Armstrong, Michelle; Jameson, J. Brian, II; Perry, Steven; Joshi, Netra; Holman, Theodore R.] Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA.
RP Maloney, DJ (reprint author), NHGRI, NIH Chem Genom Ctr, NIH, 9800 Med Ctr Dr,MSC 3370, Bethesda, MD 20892 USA.
EM maloneyd@mail.nih.gov; holman@ucsc.edu
OI Taylor-Fishwick, David/0000-0002-6720-7482
FU National Institutes of Health [R01 GM56062, R00 HL089457, R01 DK 55240,
S10-RR20939]; Juvenile Diabetes Research Foundation; Molecular Libraries
Initiative of the National Institutes of Health Roadmap for Medical
Research [R03 MH081283]; California Institute for Quantitative
Biosciences
FX We thank Eric Hoobler for the 5-LOX assay, Norine Kuhn for islet
incubations and the 12-HETE ELISA, Sam Michael for assistance with the
primary HTP screen, and Paul Shinn and Danielle vanLeer for assistance
with compound management and purification. We also thank Christina Greco
for critical reading of the manuscript. Financial support was from the
National Institutes of Health (R01 GM56062 (T.RH.), R00 HL089457 (M.H.),
R01 DK 55240 (D.T.F., J.L.N.)), the Juvenile Diabetes Research
Foundation (D.T.F., T.RH., J.L.N.), and the Molecular Libraries
Initiative of the National Institutes of Health Roadmap for Medical
Research (R03 MH081283 (T.R.H.)). Additional financial support was from
NIH (S10-RR20939 (T.RH.)) and the California Institute for Quantitative
Biosciences (T.RH.) for the UCSC MS Facility.
NR 90
TC 26
Z9 26
U1 2
U2 11
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD AUG 11
PY 2011
VL 54
IS 15
BP 5485
EP 5497
DI 10.1021/jm2005089
PG 13
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 801EK
UT WOS:000293419400020
PM 21739938
ER
PT J
AU Matsuoka, RL
Chivatakarn, O
Badea, TC
Samuels, IS
Cahill, H
Katayama, KI
Kumar, SR
Suto, F
Chedotal, A
Peachey, NS
Nathans, J
Yoshida, Y
Giger, RJ
Kolodkin, AL
AF Matsuoka, Ryota L.
Chivatakarn, Onanong
Badea, Tudor C.
Samuels, Ivy S.
Cahill, Hugh
Katayama, Kei-ichi
Kumar, Sumit R.
Suto, Fumikazu
Chedotal, Alain
Peachey, Neal S.
Nathans, Jeremy
Yoshida, Yutaka
Giger, Roman J.
Kolodkin, Alex L.
TI Class 5 Transmembrane Semaphorins Control Selective Mammalian Retinal
Lamination and Function
SO NEURON
LA English
DT Article
ID GANGLION-CELLS; MOUSE RETINA; BIPOLAR CELLS; OSCILLATORY POTENTIALS;
NERVOUS-SYSTEM; IN-VIVO; B-WAVE; PATHWAY; DSCAM; RESPONSES
AB In the vertebrate retina, neurites from distinct neuronal cell types are constrained within the plexiform layers, allowing for establishment of retinal lamination. However, the mechanisms by which retinal neurites are segregated within the inner or outer plexiform layers are not known. We find that the transmembrane semaphorins Sema5A and Sema5B constrain neurites from multiple retinal neuron subtypes within the inner plexiform layer (IPL). In Serna5A(-/-); Serna5B(-/-) mice, retinal ganglion cells (RGCs) and annacrine and bipolar cells exhibit severe defects leading to neurite mistargeting into the outer portions of the retina. These targeting abnormalities are more prominent in the outer (OFF) layers of the IPL and result in functional defects in select RGC response properties. Sema5A and Sema5B inhibit retinal neurite outgrowth through PlexinA1 and PlexinA3 receptors both in vitro and in vivo. These findings define a set of ligands and receptors required for the establishment of inner retinal lamination and function.
C1 [Chivatakarn, Onanong; Giger, Roman J.] Univ Michigan, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA.
[Matsuoka, Ryota L.; Kolodkin, Alex L.] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA.
[Badea, Tudor C.; Cahill, Hugh; Nathans, Jeremy] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA.
[Matsuoka, Ryota L.; Badea, Tudor C.; Cahill, Hugh; Nathans, Jeremy; Kolodkin, Alex L.] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA.
[Samuels, Ivy S.; Peachey, Neal S.] Cleveland Clin Fdn, Cole Eye Inst, Cleveland, OH 44195 USA.
[Peachey, Neal S.] Case Western Reserve Univ, Cleveland Clin Lerner Coll Med, Dept Ophthalmol, Cleveland, OH 44195 USA.
[Katayama, Kei-ichi; Yoshida, Yutaka] Cincinnati Childrens Hosp, Med Ctr, Div Dev Biol, Cincinnati, OH 45229 USA.
[Kumar, Sumit R.] NEI, Retinal Circuit Dev & Genet Unit, Neurobiol Neurodegenerat & Repair Lab, Bethesda, MD 20892 USA.
[Suto, Fumikazu] Natl Ctr Neurol & Psychiat, Dept Ultrastruct Res, Kodaira, Tokyo 1878502, Japan.
[Chedotal, Alain] INSERM, UMR S968, F-75012 Paris, France.
[Chedotal, Alain] Univ Paris 06, UMR S968, F-75012 Paris, France.
[Chedotal, Alain] CNRS, Inst Vis, UMR 7210, F-75012 Paris, France.
[Samuels, Ivy S.; Peachey, Neal S.] Cleveland VA Med Ctr, Res Serv, Cleveland, OH 44106 USA.
RP Giger, RJ (reprint author), Univ Michigan, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA.
EM rgiger@umich.edu; kolodkin@jhmi.edu
RI Katayama, Kei-ichi/J-4699-2013;
OI Katayama, Kei-ichi/0000-0003-0527-4644; Chedotal,
Alain/0000-0001-7577-3794
FU Nakajima Foundation [R01 NS35165]; NRSA [F31NS056558-01A1]; Veterans
Administration; Foundation Fighting Blindness; Foundation pour la
Rechereche Medicale; [R01 NS065048]; [R01 NS047333]
FX We thank K.-W. Yau and T. Xue for the Opn4Tau-LacZ/Tau-LacZ
mice, M. Tessier-Lavigne for the PlexA3-/- mice, B. Howell
for the Dab-1 antibody, and F. Haeseleer for the CaBP5 antibody. We also
thank D. Kantor, S. Kozlov, C. Hawkins, and K. Takamiya for their
assistance with the generation of the Sema5A-/- and
Sema5B-/- mice. We thank M. Riccomagno, K. Mandai, S.-H.
Wang, Y. Duan, and T. Tran for helpful suggestions and discussions
throughout this project, D. Johnson for assistance with mouse
experiments, and members of the Kolodkin laboratory for assistance. This
work was supported by R01 NS35165 (to A.L.K.), a predoctoral fellowship
from the Nakajima Foundation (to R.L.M.), NRSA F31NS056558-01A1 (to
O.C.), the Veterans Administration (to I.S.S. and N.S.P.), the
Foundation Fighting Blindness (to N.S.P.), R01 NS065048 (to Y.Y.), the
Foundation pour la Rechereche Medicale (Programme equipe FRM) (to A.C.),
and R01 NS047333 (to R.J.G.). A.L.K. and J.N. are investigators of the
Howard Hughes Medical Institute.
NR 55
TC 67
Z9 68
U1 0
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD AUG 11
PY 2011
VL 71
IS 3
BP 460
EP 473
DI 10.1016/j.neuron.2011.06.009
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 808PU
UT WOS:000293991700010
PM 21835343
ER
PT J
AU Hinch, AG
Tandon, A
Patterson, N
Song, YL
Rohland, N
Palmer, CD
Chen, GK
Wang, K
Buxbaum, SG
Akylbekova, EL
Aldrich, MC
Ambrosone, CB
Amos, C
Bandera, EV
Berndt, SI
Bernstein, L
Blot, WJ
Bock, CH
Boerwinkle, E
Cai, QY
Caporaso, N
Casey, G
Cupples, LA
Deming, SL
Diver, WR
Divers, J
Fornage, M
Gillanders, EM
Glessner, J
Harris, CC
Hu, JJ
Ingles, SA
Isaacs, W
John, EM
Kao, WHL
Keating, B
Kittles, RA
Kolonel, LN
Larkin, E
Le Marchand, L
McNeill, LH
Millikan, RC
Murphy, A
Musani, S
Neslund-Dudas, C
Nyante, S
Papanicolaou, GJ
Press, MF
Psaty, BM
Reiner, AP
Rich, SS
Rodriguez-Gil, JL
Rotter, JI
Rybicki, BA
Schwartz, AG
Signorello, LB
Spitz, M
Strom, SS
Thun, MJ
Tucker, MA
Wang, ZM
Wiencke, JK
Witte, JS
Wrensch, M
Wu, XF
Yamamura, Y
Zanetti, KA
Zheng, W
Ziegler, RG
Zhu, XF
Redline, S
Hirschhorn, JN
Henderson, BE
Taylor, HA
Price, AL
Hakonarson, H
Chanock, SJ
Haiman, CA
Wilson, JG
Reich, D
Myers, SR
AF Hinch, Anjali G.
Tandon, Arti
Patterson, Nick
Song, Yunli
Rohland, Nadin
Palmer, Cameron D.
Chen, Gary K.
Wang, Kai
Buxbaum, Sarah G.
Akylbekova, Ermeg L.
Aldrich, Melinda C.
Ambrosone, Christine B.
Amos, Christopher
Bandera, Elisa V.
Berndt, Sonja I.
Bernstein, Leslie
Blot, William J.
Bock, Cathryn H.
Boerwinkle, Eric
Cai, Qiuyin
Caporaso, Neil
Casey, Graham
Cupples, L. Adrienne
Deming, Sandra L.
Diver, W. Ryan
Divers, Jasmin
Fornage, Myriam
Gillanders, Elizabeth M.
Glessner, Joseph
Harris, Curtis C.
Hu, Jennifer J.
Ingles, Sue A.
Isaacs, William
John, Esther M.
Kao, W. H. Linda
Keating, Brendan
Kittles, Rick A.
Kolonel, Laurence N.
Larkin, Emma
Le Marchand, Loic
McNeill, Lorna H.
Millikan, Robert C.
Murphy, Adam
Musani, Solomon
Neslund-Dudas, Christine
Nyante, Sarah
Papanicolaou, George J.
Press, Michael F.
Psaty, Bruce M.
Reiner, Alex P.
Rich, Stephen S.
Rodriguez-Gil, Jorge L.
Rotter, Jerome I.
Rybicki, Benjamin A.
Schwartz, Ann G.
Signorello, Lisa B.
Spitz, Margaret
Strom, Sara S.
Thun, Michael J.
Tucker, Margaret A.
Wang, Zhaoming
Wiencke, John K.
Witte, John S.
Wrensch, Margaret
Wu, Xifeng
Yamamura, Yuko
Zanetti, Krista A.
Zheng, Wei
Ziegler, Regina G.
Zhu, Xiaofeng
Redline, Susan
Hirschhorn, Joel N.
Henderson, Brian E.
Taylor, Herman A., Jr.
Price, Alkes L.
Hakonarson, Hakon
Chanock, Stephen J.
Haiman, Christopher A.
Wilson, James G.
Reich, David
Myers, Simon R.
TI The landscape of recombination in African Americans
SO NATURE
LA English
DT Article
ID HUMAN GENOME; MEIOTIC RECOMBINATION; MAP; HUMANS; PRDM9; POPULATIONS;
SEQUENCE; HOTSPOTS; GENE; INSTABILITY
AB Recombination, together with mutation, gives rise to genetic variation in populations. Here we leverage the recent mixture of people of African and European ancestry in the Americas to build a genetic map measuring the probability of crossing over at each position in the genome, based on about 2.1 million crossovers in 30,000 unrelated African Americans. At intervals of more than three megabases it is nearly identical to a map built in Europeans. At finer scales it differs significantly, and we identify about 2,500 recombination hotspots that are active in people of West African ancestry but nearly inactive in Europeans. The probability of a crossover at these hotspots is almost fully controlled by the alleles an individual carries at PRDM9(P value <10(-245)). We identify a 17-base-pair DNA sequence motif that is enriched in these hotspots, and is an excellent match to the predicted binding target of PRDM9 alleles common in West Africans and rare in Europeans. Sites of this motif are predicted to be risk loci for disease-causing genomic rearrangements in individuals carrying these alleles. More generally, this map provides a resource for research in human genetic variation and evolution.
C1 [Tandon, Arti; Patterson, Nick; Rohland, Nadin; Reich, David] Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA.
[Hinch, Anjali G.; Myers, Simon R.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
[Tandon, Arti; Rohland, Nadin; Reich, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Song, Yunli; Myers, Simon R.] Univ Oxford, Dept Stat, Oxford OX1 3TG, England.
[Palmer, Cameron D.; Hirschhorn, Joel N.] Broad Inst, Program Med & Populat Genet, Cambridge Ctr 7, Cambridge, MA 02142 USA.
[Palmer, Cameron D.; Hirschhorn, Joel N.] Childrens Hosp Boston, Div Endocrinol, Boston, MA 02115 USA.
[Palmer, Cameron D.; Hirschhorn, Joel N.] Childrens Hosp Boston, Div Genet, Boston, MA 02115 USA.
[Palmer, Cameron D.; Hirschhorn, Joel N.] Childrens Hosp Boston, Program Genom, Boston, MA 02115 USA.
[Chen, Gary K.; Casey, Graham; Ingles, Sue A.; Press, Michael F.; Henderson, Brian E.; Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Chen, Gary K.; Casey, Graham; Ingles, Sue A.; Press, Michael F.; Henderson, Brian E.; Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Pathol, Los Angeles, CA 90033 USA.
[Wang, Kai] Univ So Calif, Zilkha Neurogenet Inst, Los Angeles, CA 90089 USA.
[Wang, Kai; Glessner, Joseph; Keating, Brendan; Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA.
[Buxbaum, Sarah G.; Akylbekova, Ermeg L.] Jackson State Univ, Jackson Heart Study Coordinating Ctr, Jackson, MS 39213 USA.
[Akylbekova, Ermeg L.; Musani, Solomon; Taylor, Herman A., Jr.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
[Aldrich, Melinda C.] Vanderbilt Univ, Sch Med, Dept Thorac Surg, Nashville, TN 37203 USA.
[Aldrich, Melinda C.; Blot, William J.; Cai, Qiuyin; Deming, Sandra L.; Signorello, Lisa B.; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Div Epidemiol,Dept Med, Nashville, TN 37203 USA.
[Aldrich, Melinda C.; Blot, William J.; Cai, Qiuyin; Deming, Sandra L.; Signorello, Lisa B.; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37203 USA.
[Ambrosone, Christine B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[Amos, Christopher; Spitz, Margaret; Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Div Canc Prevent & Populat Sci, Houston, TX 77030 USA.
[Bandera, Elisa V.] Canc Inst New Jersey, New Brunswick, NJ 08903 USA.
[Berndt, Sonja I.; Caporaso, Neil; Tucker, Margaret A.; Ziegler, Regina G.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Bernstein, Leslie] City Hope Natl Med Ctr, Div Canc Etiol, Dept Populat Sci, Beckman Res Inst, Duarte, CA 91010 USA.
[Blot, William J.; Signorello, Lisa B.] Int Epidemiol Inst, Rockville, MD 20850 USA.
[Bock, Cathryn H.; Schwartz, Ann G.] Wayne State Univ Med, Karmanos Canc Inst, Detroit, MI 48201 USA.
[Bock, Cathryn H.; Schwartz, Ann G.] Wayne State Univ Med, Dept Oncol, Detroit, MI 48201 USA.
[Boerwinkle, Eric] Univ Texas Houston, Ctr Human Genet, Houston, TX 77030 USA.
[Boerwinkle, Eric] Univ Texas Houston, Div Epidemiol, Houston, TX 77030 USA.
[Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[Cupples, L. Adrienne] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.
[Diver, W. Ryan; Thun, Michael J.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30303 USA.
[Divers, Jasmin] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Winston Salem, NC 27157 USA.
[Fornage, Myriam; Gillanders, Elizabeth M.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Inst Mol Med, Houston, TX 77030 USA.
[Fornage, Myriam; Gillanders, Elizabeth M.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Div Epidemiol, Houston, TX 77030 USA.
[Zanetti, Krista A.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Harris, Curtis C.; Zanetti, Krista A.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Hu, Jennifer J.; Rodriguez-Gil, Jorge L.] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA.
[Hu, Jennifer J.; Rodriguez-Gil, Jorge L.] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA.
[Isaacs, William] Johns Hopkins Hosp & Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21287 USA.
[John, Esther M.] Canc Prevent Inst Calif, Fremont, CA 94538 USA.
[John, Esther M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[John, Esther M.] Stanford Canc Ctr, Stanford, CA 94305 USA.
[Kao, W. H. Linda] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Kittles, Rick A.] Univ Illinois, Dept Med, Chicago, IL 60607 USA.
[Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96813 USA.
[Larkin, Emma] Vanderbilt Univ, Med Ctr, Div Allergy Pulm & Crit Care, Dept Med,Med Ctr E, Nashville, TN 37232 USA.
[McNeill, Lorna H.] Univ Texas MD Anderson Canc Ctr, Dept Hlth Dispar Res, Div OVP Canc Prevent & Populat Sci, Houston, TX 77030 USA.
[McNeill, Lorna H.] Univ Texas MD Anderson Canc Ctr, Ctr Community Implementat & Disseminat Res, Duncan Family Inst, Houston, TX 77030 USA.
[Millikan, Robert C.; Nyante, Sarah] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA.
[Millikan, Robert C.; Nyante, Sarah] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Murphy, Adam] Northwestern Univ, Dept Urol, Chicago, IL 60611 USA.
[Neslund-Dudas, Christine; Rybicki, Benjamin A.] Henry Ford Hosp, Dept Publ Hlth Sci, Detroit, MI 48202 USA.
[Papanicolaou, George J.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.
[Psaty, Bruce M.] Grp Hlth Res Inst, Seattle, WA 98101 USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Seattle, WA 98101 USA.
[Reiner, Alex P.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA.
[Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Wang, Zhaoming] Natl Canc Inst Frederick, Core Genotype Facil, SAIC Frederick Inc, Frederick, MD 20877 USA.
[Witte, John S.] Univ Calif San Francisco, Dept Epidemiol & Biostat, Inst Human Genet, San Francisco, CA 94158 USA.
[Witte, John S.] Univ Calif San Francisco, Dept Urol, Inst Human Genet, San Francisco, CA 94158 USA.
[Zhu, Xiaofeng] Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
[Redline, Susan] Brigham & Womens Hosp, Dept Med, Div Sleep Med, Boston, MA 02115 USA.
[Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Taylor, Herman A., Jr.] Jackson State Univ, Jackson, MS 39217 USA.
[Taylor, Herman A., Jr.] Tougaloo Coll, Tougaloo, MS 39174 USA.
[Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Hakonarson, Hakon] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA.
[Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
RP Reich, D (reprint author), Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA.
EM reich@genetics.med.harvard.edu; myers@stats.ox.ac.uk
RI Aldrich, Melinda/C-7783-2013; Bandera, Elisa/M-4169-2014; Myers,
Simon/A-6792-2015; Tucker, Margaret/B-4297-2015; Buxbaum,
Sarah/E-1970-2013
OI Bandera, Elisa/0000-0002-8789-2755; Myers, Simon/0000-0002-2585-9626;
Cupples, L. Adrienne/0000-0003-0273-7965; Buxbaum,
Sarah/0000-0002-4886-3564
FU Wellcome Trust; NIH [HL084107, GM091332]; National Heart, Lung and Blood
Institute [HHSN268200960009C]; Children's Hospital of Philadelphia;
Landenberger Foundation; Cotswold Foundation; DoD; Norris Foundation;
MEC [CA63464, CA54281]; CARE [HD33175]; WCHS [CA100598]; DAMD
[170100334, 17966071, W81XWH0710645, W81XWH0710203, W81XWH0610066];
Breast Cancer Research Foundation; SFBC [CA77305]; CBCS [CA58223,
ES10126]; PLCO; NHBS [CA100374]; WFBC [R01-CA73629]; CPS-II (the
American Cancer Society); LAAPC [99-00524V-10258, PC35139, DP000807];
MEC; MDA [CA68578, CA140388, ES007784]; GECAP [ES011126]; CaP Genes
[CA88164]; IPCG [W81XWH0710122]; DCPC [GM08016]; SCCS [CA092447,
CA68485]; University Cancer Foundation; Duncan Family institute; Center
for Community; Implementation and Dissemination Research Core; Maryland
Studies; [CA1326792]; [CA148085]; [HG004726]; [CA060691];
[CA87895]; [PC35145]; [CA22453]; [ES06717]; [CA55769]; [CA127219];
[CA1116460S1]; [CA1116460]; [CA121197]; [CA141716]; [CA121197S2];
[CPRIT RP100443]; [CA148127]; [DAMD W81XWH0710645]
FX We are grateful to the participants who donated DNA samples, to D.
Altshuler, J. Buard, K. Bryc, J. Kovacs, B. de Massy, G. McVean, B.
Pasaniuc and S. Sankararaman for conversations and critiques, and to A.
Auton for facilitating analysis of the 1000 Genomes Project data.
Analysis was supported by the Wellcome Trust and NIH grants HL084107 and
GM091332. CARe was supported by a contract from the National Heart, Lung
and Blood Institute (HHSN268200960009C) to create a phenotype and
genotype database for dissemination to the biomedical research
community. Eight parent studies contributed phenotypic data and DNA
samples through the Broad Institute (N01-HC-65226): the Atherosclerosis
Risk in Communities study (ARIC), the Cleveland Family Study (CFS), the
Coronary Artery Risk Development in Young Adults study (CARDIA), the
Jackson Heart Study (JHS), the Multi-Ethnic Study of Atherosclerosis
(MESA) study, the Cardiovascular Health Study (CHS), the Framingham
Heart Study (FHS) and the Sleep Heart Health Study (SHHS). Support for
CARe also came from the individual research institutions, investigators,
field staff and study participants. Individual funding information is
available at
http://public.nhlbi.nih.gov/GeneticsGenomics/home/care.aspx. All
genome-wide genotyping of samples from the Children's Hospital of
Pennsylvania (CHOP) was supported by an Institutional Development Award
to the Center for Applied Genomics from the Children's Hospital of
Philadelphia, a research award from the Landenberger Foundation and the
Cotswold Foundation. We thank all study participants and the staff at
the Center for Applied Genomics for performing the genotyping. The
African American Breast Cancer Consortium (AABCC) was supported by a DoD
Breast Cancer Research Program Era of Hope Scholar Award to C. A. H. and
the Norris Foundation, and by grants to the component studies: MEC
(CA63464, CA54281); CARE (HD33175); WCHS (CA100598, DAMD 170100334,
Breast Cancer Research Foundation); SFBC (CA77305, DAMD 17966071); CBCS
(CA58223, ES10126), PLCO (NCI Intramural Research Program); NHBS
(CA100374); WFBC (R01-CA73629); and CPS-II (the American Cancer
Society). The African American Prostate Cancer Consortium(AAPCC) was
supported by grants CA63464, CA54281, CA1326792, CA148085 and HG004726,
and by grants to the component studies: PLCO (NCI Intramural Research
Program), LAAPC (Cancer Research Fund 99-00524V-10258), both MEC and
LAAPC (PC35139, DP000807); MDA (CA68578, CA140388, ES007784, DAMD
W81XWH0710645); GECAP (ES011126); CaP Genes (CA88164); IPCG
(W81XWH0710122); DCPC (GM08016, DAMD W81XWH0710203, DAMD W81XWH0610066);
and SCCS (CA092447, CA68485). The African American Lung Cancer
Consortium(AALCC) was supported by grants CA060691, CA87895, PC35145 and
CA22453, CA68578, CA140388, ES007784, ES06717, CA55769, CA127219,
CA1116460S1, CA1116460, CA121197, CA141716, CA121197S2, CPRIT RP100443,
CA148127, DAMD W81XWH0710645, University Cancer Foundation, Duncan
Family institute, Center for Community, Implementation and Dissemination
Research Core, and by grants to the component studies: PLCO and the
Maryland Studies (NCI Intramural Research Program), LAAPC (Cancer
Research Fund 99-00524V-10258), and both MEC and LAAPC (PC35139,
DP000807).
NR 29
TC 121
Z9 123
U1 2
U2 27
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD AUG 11
PY 2011
VL 476
IS 7359
BP 170
EP U67
DI 10.1038/nature10336
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 805MU
UT WOS:000293731900028
PM 21775986
ER
PT J
AU Cohen, MS
Chen, YQ
McCauley, M
Gamble, T
Hosseinipour, MC
Kumarasamy, N
Hakim, JG
Kumwenda, J
Grinsztejn, B
Pilotto, JHS
Godbole, SV
Mehendale, S
Chariyalertsak, S
Santos, BR
Mayer, KH
Hoffman, IF
Eshleman, SH
Piwowar-Manning, E
Wang, L
Makhema, J
Mills, LA
de Bruyn, G
Sanne, I
Eron, J
Gallant, J
Havlir, D
Swindells, S
Ribaudo, H
Elharrar, V
Burns, D
Taha, ET
Nielsen-Saines, K
Celentano, D
Essex, M
Fleming, TR
AF Cohen, Myron S.
Chen, Ying Q.
McCauley, Marybeth
Gamble, Theresa
Hosseinipour, Mina C.
Kumarasamy, Nagalingeswaran
Hakim, James G.
Kumwenda, Johnstone
Grinsztejn, Beatriz
Pilotto, Jose H. S.
Godbole, Sheela V.
Mehendale, Sanjay
Chariyalertsak, Suwat
Santos, Breno R.
Mayer, Kenneth H.
Hoffman, Irving F.
Eshleman, Susan H.
Piwowar-Manning, Estelle
Wang, Lei
Makhema, Joseph
Mills, Lisa A.
de Bruyn, Guy
Sanne, Ian
Eron, Joseph
Gallant, Joel
Havlir, Diane
Swindells, Susan
Ribaudo, Heather
Elharrar, Vanessa
Burns, David
Taha, Taha E.
Nielsen-Saines, Karin
Celentano, David
Essex, Max
Fleming, Thomas R.
CA HPTN 052 Study Team
TI Prevention of HIV-1 Infection with Early Antiretroviral Therapy
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; HIV-1-INFECTED PATIENTS; TRANSMISSION;
MORTALITY; INITIATION; RETHINKING; COUNTRIES; COHORT; UGANDA; MALAWI
AB Background
Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples.
Methods
In nine countries, we enrolled 1763 couples in which one partner was HIV-1-positive and the other was HIV-1-negative; 54% of the subjects were from Africa, and 50% of infected partners were men. HIV-1-infected subjects with CD4 counts between 350 and 550 cells per cubic millimeter were randomly assigned in a 1: 1 ratio to receive antiretroviral therapy either immediately (early therapy) or after a decline in the CD4 count or the onset of HIV-1-related symptoms (delayed therapy). The primary prevention end point was linked HIV-1 transmission in HIV-1-negative partners. The primary clinical end point was the earliest occurrence of pulmonary tuberculosis, severe bacterial infection, a World Health Organization stage 4 event, or death.
Results
As of February 21, 2011, a total of 39 HIV-1 transmissions were observed (incidence rate, 1.2 per 100 person-years; 95% confidence interval [CI], 0.9 to 1.7); of these, 28 were virologically linked to the infected partner (incidence rate, 0.9 per 100 person-years, 95% CI, 0.6 to 1.3). Of the 28 linked transmissions, only 1 occurred in the early-therapy group (hazard ratio, 0.04; 95% CI, 0.01 to 0.27; P<0.001). Subjects receiving early therapy had fewer treatment end points (hazard ratio, 0.59; 95% CI, 0.40 to 0.88; P = 0.01).
Conclusions
The early initiation of antiretroviral therapy reduced rates of sexual transmission of HIV-1 and clinical events, indicating both personal and public health benefits from such therapy.
C1 [Cohen, Myron S.] Univ N Carolina, Inst Global Hlth & Infect Dis, Sch Med, Chapel Hill, NC 27599 USA.
[Chen, Ying Q.; Wang, Lei] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA.
[Fleming, Thomas R.] Univ Washington, Seattle, WA 98195 USA.
[McCauley, Marybeth] Family Hlth Int, Arlington, VA USA.
[McCauley, Marybeth] Family Hlth Int, Durham, NC USA.
UNC Project, Lilongwe, Malawi.
[Kumwenda, Johnstone] Johns Hopkins Project, Coll Med, Blantyre, Malawi.
[Kumarasamy, Nagalingeswaran] YR Gaitonade Ctr AIDS Res & Educ, Chennai, Tamil Nadu, India.
[Godbole, Sheela V.; Mehendale, Sanjay] Natl AIDS Res Inst, Pune, Maharashtra, India.
[Hakim, James G.] Univ Zimbabwe, Harare, Zimbabwe.
[Grinsztejn, Beatriz] Fiocruz MS, Inst Pesquisa Clin Evandro Chagas, BR-21045900 Rio De Janeiro, Brazil.
[Pilotto, Jose H. S.] Fiocruz MS, Hosp Geral de Nova Iguacu, BR-21045900 Rio De Janeiro, Brazil.
[Pilotto, Jose H. S.] Lab AIDS & Imunol Mol IOC Fiocurz, BR-21045900 Rio De Janeiro, Brazil.
[Chariyalertsak, Suwat] Chiang Mai Univ, Res Inst Hlth Sci, Chiang Mai 50000, Thailand.
[Santos, Breno R.] Hosp Nossa Senhora da Conceicao, Porto Alegre, RS, Brazil.
[Mayer, Kenneth H.] Fenway Hlth, Boston, MA USA.
[Ribaudo, Heather; Essex, Max] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Eshleman, Susan H.; Piwowar-Manning, Estelle; Gallant, Joel] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Taha, Taha E.; Celentano, David] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Makhema, Joseph] Botswana Harvard AIDS Inst, Gaborone, Botswana.
[Mills, Lisa A.] Ctr Dis Control & Prevent CDC, Div HIV AIDS Prevent, Kenya Med Res Inst, CDC Res & Publ Hlth Collaborat HIV Res Branch, Kisumu, Kenya.
[de Bruyn, Guy] Univ Witwatersrand, Perinatal HIV Res Unit, Johannesburg, South Africa.
[Sanne, Ian] Univ Witwatersrand, Dept Med, ZA-2001 Johannesburg, South Africa.
[Havlir, Diane] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Swindells, Susan] Univ Nebraska Med Ctr, Omaha, NE USA.
[Elharrar, Vanessa; Burns, David] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA.
[Nielsen-Saines, Karin] David Geffen UCLA Sch Med, Los Angeles, CA USA.
RP Cohen, MS (reprint author), Univ N Carolina, Inst Global Hlth & Infect Dis, Sch Med, Suite 2115,Bioinformat Bldg,130 Mason Farm Rd,CB, Chapel Hill, NC 27599 USA.
EM mscohen@med.unc.edu
RI Hendrix, Craig/G-4182-2014;
OI Hendrix, Craig/0000-0002-5696-8665; Sahay, Seema/0000-0001-6064-827X;
Moyo, Sikhulile/0000-0003-3821-4592
FU National Institute of Allergy and Infectious Diseases; National
Institute of Allergy and Infectious Diseases [UM1-AI068619,
U01-AI068619, UM1-AI068613, U01-AI068613, UM1-AI068617, U01-AI068617];
Abbott Virology; Roche Diagnostics; Monogram Biosciences; Sanofi
Pasteur; Merck; Bristol-Myers Squibb; GlaxoSmithKline; ViiV Healthcare;
Gilead Sciences and Tibotec; Roche; Tibotec Therapeutics; Pfizer;
Sangamo BioSciences; Koronis
FX Funded by the National Institute of Allergy and Infectious Diseases and
others; HPTN 052 ClinicalTrials.gov number, NCT00074581.); Supported by
the HIV Prevention Trials Network (HPTN) and by grants (UM1-AI068619 and
U01-AI068619; UM1-AI068613 and U01-AI068613, to the HPTN Network
Laboratory; and UM1-AI068617 and U01-AI068617, to the HPTN Statistical
and Data Management Center) from the National Institute of Allergy and
Infectious Diseases. Study drugs were donated by Abbott Laboratories,
Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences,
GlaxoSmithKline/ViiV Healthcare, and Merck.; Dr. Hosseinipour reports
receiving lecture fees from Abbott Virology; Dr. Eshleman, consulting
fees from Roche Diagnostics, lecture fees and samples or laboratory
reagents from Abbott Diagnostics and Celera Diagnostics, and lecture
fees from Monogram Biosciences; Dr. Mills, grant support from
GlaxoSmithKline; Dr. de Bruyn, travel support from Sanofi Pasteur; Dr.
Eron, consulting fees and grant support from Merck, Bristol-Myers
Squibb, GlaxoSmithKline, and ViiV Healthcare, consulting fees from
Gilead Sciences and Tibotec, and lecture fees from Bristol-Myers Squibb
and Roche; Dr. Gallant, consulting fees from Abbott Laboratories,
Bristol-Myers Squibb, Gilead Sciences, Merck, Tibotec Therapeutics, ViiV
Healthcare, GlaxoSmithKline, Pfizer, Sangamo BioSciences, and Koronis,
grant support and travel support from Gilead Sciences, and lecture fees
from Monogram Biosciences; Dr. Havlir, study drug from Abbott; and Dr.
Swindells, consulting fees from Gilead Sciences and Abbott Diagnostics
and grant support from Pfizer, GlaxoSmithKline, and Bristol- Myers
Squibb. No other potential conflict of interest relevant to this article
was reported.
NR 36
TC 2808
Z9 2881
U1 48
U2 347
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD AUG 11
PY 2011
VL 365
IS 6
BP 493
EP 505
DI 10.1056/NEJMoa1105243
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA 805MW
UT WOS:000293732100005
PM 21767103
ER
PT J
AU Elinoff, JM
Salit, RB
Ackerman, HC
AF Elinoff, Jason M.
Salit, Rachel B.
Ackerman, Hans C.
TI The Tumor Lysis Syndrome
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Elinoff, Jason M.] Natl Inst Hlth, Ctr Clin, Bethesda, MD 20892 USA.
[Salit, Rachel B.] NCI, Rockville, MD USA.
[Ackerman, Hans C.] NIAID, Bethesda, MD 20892 USA.
RP Elinoff, JM (reprint author), Natl Inst Hlth, Ctr Clin, Bethesda, MD 20892 USA.
EM hans.ackerman@nih.gov
FU Intramural NIH HHS [ZIA AI001150-02]
NR 5
TC 3
Z9 3
U1 0
U2 1
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD AUG 11
PY 2011
VL 365
IS 6
BP 571
EP 572
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 805MW
UT WOS:000293732100023
PM 21830982
ER
PT J
AU Mikhail, IJ
Purdy, JB
Dimock, DS
Thomas, VM
Muldoon, NA
Clauss, SB
Cross, RR
Pettigrew, RI
Hazra, R
Hadigan, C
Gharib, AM
AF Mikhail, Irene J.
Purdy, Julia B.
Dimock, David S.
Thomas, Vijaya M.
Muldoon, Nancy A.
Clauss, Sarah B.
Cross, Russell R.
Pettigrew, Roderic I.
Hazra, Rohan
Hadigan, Colleen
Gharib, Ahmed M.
TI HIGH RATE OF CORONARY ARTERY ABNORMALITIES IN ADOLESCENTS AND YOUNG
ADULTS INFECTED WITH HUMAN IMMUNODEFICIENCY VIRUS EARLY IN LIFE
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Article
DE HIV; pediatric; coronary artery abnormality; coronary MRI;
cardiovascular
ID HIV-INFECTION; CARDIOVASCULAR-DISEASE; RISK-FACTORS; ATHEROSCLEROSIS;
ANGIOGRAPHY; THICKNESS; CHILDREN
AB We completed a cross-sectional study of individuals infected with human immunodeficiency virus in early childhood using cardiac magnetic resonance imaging and magnetic resonance angiography. Coronary artery abnormality (CAA) was defined by the presence of luminal narrowing and irregularity of the coronary vessel wall. More than 50% of participants (14/27) had evidence of CAA. Individuals had a high rate of CAA, suggesting possible early atherosclerosis.
C1 [Mikhail, Irene J.; Dimock, David S.; Thomas, Vijaya M.; Hadigan, Colleen] NIAID, NIH, Bethesda, MD 20892 USA.
[Purdy, Julia B.; Muldoon, Nancy A.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Clauss, Sarah B.; Cross, Russell R.] Childrens Natl Med Ctr, Dept Cardiol, Washington, DC 20010 USA.
[Pettigrew, Roderic I.; Gharib, Ahmed M.] NIDDK, Integrat Cardiovasc Imaging Sect, NIH, Bethesda, MD USA.
[Hazra, Rohan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Mikhail, IJ (reprint author), 9000 Rockville Pike,MCS 1662,Bldg 10,Room 2C145, Bethesda, MD 20892 USA.
EM jacoubi@mail.nih.gov
RI Gharib, Ahmed/O-2629-2016
OI Gharib, Ahmed/0000-0002-2476-481X
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health, Bethesda, MD
FX Supported by Division of Intramural Research, National Institute of
Allergy and Infectious Diseases, National Institutes of Health,
Bethesda, MD.
NR 11
TC 6
Z9 6
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 AUG 11
PY 2011
VL 30
IS 8
BP 710
EP 712
DI 10.1097/INF.0b013e31820f6575
PG 3
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA 796PN
UT WOS:000293064200020
PM 21307818
ER
PT J
AU Boutte, AM
McDonald, WH
Shyr, Y
Yang, L
Lin, PC
AF Boutte, Angela M.
McDonald, W. Hayes
Shyr, Yu
Yang, Li
Lin, P. Charles
TI Characterization of the MDSC Proteome Associated with Metastatic Murine
Mammary Tumors Using Label-Free Mass Spectrometry and Shotgun Proteomics
SO PLOS ONE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MYELOID CELLS; SUPPRESSOR-CELLS;
BREAST-CANCER; TISSUE TRANSGLUTAMINASE; PEPTIDE IDENTIFICATION;
TRANSFORMED-CELLS; CATHEPSIN-B; IN-VIVO; EXPRESSION
AB Expansion of Gr-1+/CD11b+ myeloid derived suppressor cells (MDSCs) is governed by the presence of increasingly metastatic, malignant primary tumors. Metastasis, not the primary tumor, is often the cause of mortality. This study sought to fully characterize the MDSC proteome in response to metastatic and non-metastatic mammary tumors using label-free mass spectrometry shotgun proteomics in a mouse model with tumor cell lines, 67NR and 4T1, derived from the same tumor. 67NR cells form only primary mammary tumors, whereas 4T1 cells readily metastasize to the lungs, lymph nodes, and blood. Overall analysis identified a total of 2825 protein groups with a 0.78% false discovery rate. Of the 2814 true identifications, 43 proteins were exclusive to the 67NR group, 153 were exclusive to the 4T1 group, and 2618 were shared. Among the shared cohort, 26 proteins were increased and 31 were decreased in the metastatic 4T1 cohort compared to non-metastatic 67NR controls after filtering. MDSCs selectively express proteins involved in the c-glutamyl transferase, glutathione synthase pathways, CREB transcription factor signaling, and other pathways involved in platelet aggregation, as well as lipid and amino acid metabolism, in response to highly metastatic 4T1 tumors. Cell cycle regulation dominated protein pathways and ontological groups of the 67NR non-metastatic group. Not only does this study provide a starting point to identify potential biomarkers of metastasis expressed by MDSCs; it identifies critical pathways that are unique to non-metastatic and metastatic conditions. Therapeutic interventions aimed at these pathways in MDSC may offer a new route to control malignancy and metastasis.
C1 [Boutte, Angela M.] Vanderbilt Univ, Med Ctr, Dept Canc Biol, Nashville, TN 37240 USA.
[McDonald, W. Hayes] Vanderbilt Univ, Dept Biochem, Med Ctr, Nashville, TN 37232 USA.
[Shyr, Yu] Vanderbilt Univ, Med Ctr, Dept Biostat, Nashville, TN USA.
[Yang, Li; Lin, P. Charles] NIH, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Boutte, AM (reprint author), Vanderbilt Univ, Med Ctr, Dept Canc Biol, Nashville, TN 37240 USA.
EM angela.boutte@alumni.vanderbilt.edu; p.lin@nih.gov
RI McDonald, W. Hayes/B-4109-2016
OI McDonald, W. Hayes/0000-0002-3510-426X
FU NIH [1F32CA136118, UL1 RR 024975, CA108856, NS45888, AR053718]
FX This work is supported in part by grants from NIH (1F32CA136118 and UL1
RR 024975) to AMB and NIH (CA108856, NS45888 and AR053718) to PCL. No
additional external funding was received for this study. The funding
agencies had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 63
TC 13
Z9 14
U1 1
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 10
PY 2011
VL 6
IS 8
AR e22446
DI 10.1371/journal.pone.0022446
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 827UM
UT WOS:000295454200010
PM 21853032
ER
PT J
AU Cooper, MT
Kennison, JA
AF Cooper, Monica T.
Kennison, James A.
TI Molecular Genetic Analyses of Polytene Chromosome Region 72A-D in
Drosophila melanogaster Reveal a Gene Desert in 72D
SO PLOS ONE
LA English
DT Article
ID INDUCED MUTATIONS; GENOME; IDENTIFICATION; SEQUENCE; EXPRESSION;
PROJECT; PROTEIN; BRAHMA; SCREEN; BLAT
AB We have investigated a region of similar to 310 kb of genomic DNA within polytene chromosome subdivisions 72A to 72D of Drosophila melanogaster. This region includes 57 predicted protein-coding genes. Seventeen of these genes are in six clusters that appear to have arisen by tandem duplication. Within this region we found 23 complementation groups that are essential for zygotic viability, and we have identified the transcription units for 18 of the 23. We also found a 55 kb region in 72D that is nonessential. Flies deficient for this region are viable and fertile. Within this nonessential region are 48 DNA sequences of 12 to 33 base pairs that are completely conserved among 12 distantly related Drosophila species. These sequences do not have the evolutionary signature of conserved protein-coding DNA sequences, nor do they appear to encode microRNAs, however, the strong selection suggests functions in wild populations that are not apparent in laboratory cultures. This region resembles dispensable gene deserts previously characterized in the mouse genome.
C1 [Cooper, Monica T.; Kennison, James A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
RP Cooper, MT (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
EM Jim_Kennison@nih.gov
FU National Institutes of Health, NICHD
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, NICHD. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 35
TC 2
Z9 2
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 10
PY 2011
VL 6
IS 8
AR e23509
DI 10.1371/journal.pone.0023509
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 827UM
UT WOS:000295454200091
PM 21853143
ER
PT J
AU Crivat, G
Tokumasu, F
Sa, JM
Hwang, J
Wellems, TE
AF Crivat, Georgeta
Tokumasu, Fuyuki
Sa, Juliana Martha
Hwang, Jeeseong
Wellems, Thomas E.
TI Tetracysteine-Based Fluorescent Tags to Study Protein Localization and
Trafficking in Plasmodium falciparum-Infected Erythrocytes
SO PLOS ONE
LA English
DT Article
ID LIVING CELLS; LIVE CELLS; MEMBRANE PROTEIN-1; HOST ERYTHROCYTE;
CYTOADHERENCE; GREEN; EXPRESSION; VIRULENCE; SURFACE; PFEMP1
AB Plasmodium falciparum (Pf) malaria parasites remodel host erythrocytes by placing membranous structures in the host cell cytoplasm and inserting proteins into the surrounding erythrocyte membranes. Dynamic imaging techniques with high spatial and temporal resolutions are required to study the trafficking pathways of proteins and the time courses of their delivery to the host erythrocyte membrane.
Methodology and Findings: Using a tetracysteine (TC) motif tag and TC-binding biarsenical fluorophores (BAFs) including fluorescein arsenical hairpin (FlAsH) and resorufin arsenical hairpin (ReAsH), we detected knob-associated histidine-rich protein (KAHRP) constructs in Pf-parasitized erythrocytes and compared their fluorescence signals to those of GFP (green fluorescent protein)-tagged KAHRP. Rigorous treatment with BAL (2, 3 dimercaptopropanol; British anti-Lewisite) was required to reduce high background due to nonspecific BAF interactions with endogenous cysteine-rich proteins. After this background reduction, similar patterns of fluorescence were obtained from the TC- and GFP-tagged proteins. The fluorescence from FlAsH and ReAsH-labeled protein bleached at faster rates than the fluorescence from GFP-labeled protein.
Conclusion: While TC/BAF labeling to Pf-infected erythrocytes is presently limited by high background signals, it may offer a useful complement or alternative to GFP labeling methods. Our observations are in agreement with the currently-accepted model of KAHRP movement through the cytoplasm, including transient association of KAHRP with Maurer's clefts before its incorporation into knobs in the host erythrocyte membrane.
C1 [Crivat, Georgeta; Tokumasu, Fuyuki; Sa, Juliana Martha; Wellems, Thomas E.] NIAID, Lab Malaria & Vector Res, Malaria Genet Sect, NIH, Bethesda, MD 20892 USA.
[Crivat, Georgeta; Hwang, Jeeseong] Natl Inst Stand & Technol, Phys Measurement Lab, Biophys Grp, Opt Technol Div, Gaithersburg, MD 20899 USA.
RP Crivat, G (reprint author), NIAID, Lab Malaria & Vector Res, Malaria Genet Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM twellems@niaid.nih.gov
RI Sanders, Susan/G-1957-2011;
OI Tokumasu, Fuyuki/0000-0003-2790-1071
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases; National Institute of Standards and Technology
(NIST); National Research Council at NIST; National Institute of Allergy
and Infectious Diseases of the National Institutes of Health (NIH);
National Institute for Biomedical Imaging and Bioengineering of the NIH
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases, and by the Innovations in Measurement Science
program of the National Institute of Standards and Technology (NIST). GC
held a National Research Council Research Associateship Award at NIST
and National Institute of Allergy and Infectious Diseases of the
National Institutes of Health (NIH); funding for the award was provided
by NIST and the Intramural Program of the National Institute for
Biomedical Imaging and Bioengineering of the NIH. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 50
TC 3
Z9 3
U1 0
U2 13
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 10
PY 2011
VL 6
IS 8
AR e22975
DI 10.1371/journal.pone.0022975
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 827UM
UT WOS:000295454200030
PM 21860664
ER
PT J
AU Harvey, BK
Airavaara, M
Hinzman, J
Wires, EM
Chiocco, MJ
Howard, DB
Shen, H
Gerhardt, G
Hoffer, BJ
Wang, Y
AF Harvey, Brandon K.
Airavaara, Mikko
Hinzman, Jason
Wires, Emily M.
Chiocco, Matthew J.
Howard, Douglas B.
Shen, Hui
Gerhardt, Greg
Hoffer, Barry J.
Wang, Yun
TI Targeted Over-Expression of Glutamate Transporter 1 (GLT-1) Reduces
Ischemic Brain Injury in a Rat Model of Stroke
SO PLOS ONE
LA English
DT Article
ID CEREBRAL-ISCHEMIA; NMDA RECEPTOR; UP-REGULATION; ASPARTATE; DAMAGE;
NEUROPROTECTION; INDUCTION; TOLERANCE; ELEVATION; BLOCKADE
AB Following the onset of an ischemic brain injury, the excitatory neurotransmitter glutamate is released. The excitotoxic effects of glutamate are a major contributor to the pathogenesis of a stroke. The aim of this study was to examine if overexpression of a glutamate transporter (GLT-1) reduces ischemic brain injury in a rat model of stroke. We generated an adeno-associated viral (AAV) vector expressing the rat GLT-1 cDNA (AAV-GLT1). Functional expression of AAV-GLT1 was confirmed by increased glutamate clearance rate in non-stroke rat brain as measured by in vivo amperometry. AAV-GLT1 was injected into future cortical region of infarction 3 weeks prior to 60 min middle cerebral artery occlusion (MCAo). Tissue damage was assessed at one and two days after MCAo using TUNEL and TTC staining, respectively. Behavioral testing was performed at 2, 8 and 14 days post-stroke. Animals receiving AAV-GLT1, compared to AAV-GFP, showed significant decreases in the duration and magnitude of extracellular glutamate, measured by microdialysis, during the 60 minute MCAo. A significant reduction in brain infarction and DNA fragmentation was observed in the region of AAV-GLT1 injection. Animals that received AAV-GLT1 showed significant improvement in behavioral recovery following stroke compared to the AAV-GFP group. We demonstrate that focal overexpression of the glutamate transporter, GLT-1, significantly reduces ischemia-induced glutamate overflow, decreases cell death and improves behavioral recovery. These data further support the role of glutamate in the pathogenesis of ischemic damage in brain and demonstrate that targeted gene delivery to decrease the ischemia-induced glutamate overflow reduces the cellular and behavioral deficits caused by stroke.
C1 [Harvey, Brandon K.; Airavaara, Mikko; Wires, Emily M.; Chiocco, Matthew J.; Howard, Douglas B.; Shen, Hui; Hoffer, Barry J.; Wang, Yun] Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD USA.
[Hinzman, Jason; Gerhardt, Greg] Univ Kentucky, Coll Med, Dept Anat & Neurobiol, Ctr Microelectrode Technol, Lexington, KY USA.
RP Harvey, BK (reprint author), Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD USA.
EM bharvey@mail.nih.gov
OI Airavaara, Mikko/0000-0002-2026-1609
FU National Institute on Drug Abuse; [F31NS067899]; [DA017186]
FX This study was supported by the Intramural Program of the National
Institute on Drug Abuse. In addition, support was received from
F31NS067899 (Jason Hinzman) and DA017186 (Greg Gerhardt). Because Greg
Gerhardt is an owner of Quanteon, LLC, where the microelectrodes were
purchased, it could be considered a funder, although no money was
received from Quanteon, LLC. Microelectrodes were purchased from
Quanteon, LLC because it is the only company that makes this type of
multielectrode for in vivo amperometry. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 35
TC 33
Z9 38
U1 0
U2 12
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 10
PY 2011
VL 6
IS 8
AR e22135
DI 10.1371/journal.pone.0022135
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 827UM
UT WOS:000295454200008
PM 21853027
ER
PT J
AU Safronetz, D
Haddock, E
Feldmann, F
Ebihara, H
Feldmann, H
AF Safronetz, David
Haddock, Elaine
Feldmann, Friederike
Ebihara, Hideki
Feldmann, Heinz
TI In Vitro and In Vivo Activity of Ribavirin against Andes Virus Infection
SO PLOS ONE
LA English
DT Article
ID HANTAVIRUS PULMONARY SYNDROME; TO-PERSON TRANSMISSION; SIN-NOMBRE-VIRUS;
HANTAAN VIRUS; INTRAVENOUS RIBAVIRIN; CARDIOPULMONARY SYNDROME;
ANTIVIRAL ACTIVITY; DOUBLE-BLIND; EXPERIENCE; HAMSTERS
AB In Pathogenic hantaviruses are a closely related group of rodent- borne viruses which are responsible for two distinct diseases in humans, hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome (HPS, otherwise known as hantavirus cardiopulmonary syndrome, HCPS). The antiviral effect of ribavirin against Old World hantaviruses, most notably Hantaan virus, is well documented; however, only a few studies have addressed its inhibitory effect on New World hantaviruses. In the present study, we demonstrate that ribavirin is highly active against Andes virus (ANDV), an important etiological agent of HPS, both in vitro and in vivo using a lethal hamster model of HPS. Treatment of ANDV infected Vero E6 cells with ribavirin resulted in dose-dependent reductions in viral RNA and protein as well as virus yields with a half maximal inhibitory concentration between 5 and 12.5 mu g.ml(-1). In hamsters, treatment with as little as 5 mg kg 21 day 21 was 100% effective at preventing lethal HPS disease when therapy was administered by intraperitoneal injection from day1 through day 10 post-infection. Significant reductions were observed in ANDV RNA and antigen positive cells in lung and liver tissues. Ribavirin remained completely protective when administered by intraperitoneal injections up to three days post-infection. In addition, we show that daily oral ribavirin therapy initiated 1 day post-infection and continuing for ten days is also protective against lethal ANDV disease, even at doses of 5 mg kg(-1) day(-1). Our results suggest ribavirin treatment is beneficial for postexposure prophylaxis against HPS-causing hantaviruses and should be considered in scenarios where exposure to the virus is probable. The similarities between the results obtained in this study and those from previous clinical evaluations of ribavirin against HPS, further validate the hamster model of lethal HPS and demonstrate its usefulness in screening antiviral agents against this disease.
C1 [Safronetz, David; Haddock, Elaine; Ebihara, Hideki; Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT 59840 USA.
[Feldmann, Friederike] NIAID, Off Operat & Management, Div Intramural Res, NIH, Hamilton, MT USA.
[Feldmann, Heinz] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada.
RP Safronetz, D (reprint author), NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT 59840 USA.
EM feldmannh@niaid.nih.gov
FU National Institutes of Health
FX This work was funded by the Intramural Research Program of the National
Institutes of Health. The funders had no role in the study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 31
TC 21
Z9 21
U1 1
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 10
PY 2011
VL 6
IS 8
AR e23560
DI 10.1371/journal.pone.0023560
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 827UM
UT WOS:000295454200097
PM 21853152
ER
PT J
AU Sales, KU
Hobson, JP
Wagenaar-Miller, R
Szabo, R
Rasmussen, AL
Bey, A
Shah, MF
Molinolo, AA
Bugge, TH
AF Sales, Katiuchia Uzzun
Hobson, John P.
Wagenaar-Miller, Rebecca
Szabo, Roman
Rasmussen, Amber L.
Bey, Alexandra
Shah, Maham F.
Molinolo, Alfredo A.
Bugge, Thomas H.
TI Expression and Genetic Loss of Function Analysis of the HAT/DESC Cluster
Proteases TMPRSS11A and HAT
SO PLOS ONE
LA English
DT Article
ID TRYPSIN-LIKE PROTEASE; TRANSMEMBRANE SERINE PROTEASES; PROATRIAL
NATRIURETIC PEPTIDE; AUTOSOMAL RECESSIVE DEAFNESS; SURFACE
PROTEOLYTIC-ENZYMES; AIRWAY EPITHELIAL-CELLS; CONVERTING ENZYME;
IRON-DEFICIENCY; MICE LACKING; HEARING-LOSS
AB Genome mining at the turn of the millennium uncovered a new family of type II transmembrane serine proteases (TTSPs) that comprises 17 members in humans and 19 in mice. TTSPs phylogenetically belong to one of four subfamilies: matriptase, hepsin/TMPRSS, corin and HAT/DESC. Whereas a wealth of information now has been gathered as to the physiological functions of members of the hepsin/TMPRSS, matriptase, and corin subfamilies of TTSPs, comparatively little is known about the functions of the HAT/DESC subfamily of proteases. Here we perform a combined expression and functional analysis of this TTSP subfamily. We show that the five human and seven murine HAT/DESC proteases are coordinately expressed, suggesting a level of functional redundancy. We also perform a comprehensive phenotypic analysis of mice deficient in two of the most widely expressed HAT/DESC proteases, TMPRSS11A and HAT, and show that the two proteases are dispensable for development, health, and long-term survival in the absence of external challenges or additional genetic deficits. Our comprehensive expression analysis and generation of TMPRSS11A- and HAT-deficient mutant mouse strains provide a valuable resource for the scientific community for further exploration of the HAT/DESC subfamily proteases in physiological and pathological processes.
C1 [Sales, Katiuchia Uzzun; Hobson, John P.; Wagenaar-Miller, Rebecca; Szabo, Roman; Rasmussen, Amber L.; Bey, Alexandra; Shah, Maham F.; Molinolo, Alfredo A.; Bugge, Thomas H.] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
[Wagenaar-Miller, Rebecca] Natl Inst Dent & Craniofacial Res, Div Extramural Act, NIH, Bethesda, MD USA.
[Bey, Alexandra] Duke Univ, Sch Med, Durham, NC USA.
RP Sales, KU (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
EM thomas.bugge@nih.gov
FU National Institute of Dental and Craniofacial Research
FX This work was supported by the National Institute of Dental and
Craniofacial Research Intramural Research Program. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 45
TC 14
Z9 14
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 10
PY 2011
VL 6
IS 8
AR e23261
DI 10.1371/journal.pone.0023261
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 827UM
UT WOS:000295454200058
PM 21853097
ER
PT J
AU Ibrahim, L
Duncan, W
Luckenbaugh, DA
Yuan, PX
Machado-Vieira, R
Zarate, CA
AF Ibrahim, Lobna
Duncan, Wallace
Luckenbaugh, David A.
Yuan, Peixiong
Machado-Vieira, Rodrigo
Zarate, Carlos A., Jr.
TI Rapid antidepressant changes with sleep deprivation in major depressive
disorder are associated with changes in vascular endothelial growth
factor (VEGF): A pilot study
SO BRAIN RESEARCH BULLETIN
LA English
DT Article
DE Antidepressant; Depression; Neurotrophic factors; Sleep deprivation
ID NEUROTROPHIC FACTOR BDNF; ELECTROCONVULSIVE-THERAPY ECT;
GENE-EXPRESSION; BEHAVIORAL ACTIONS; RATING-SCALE; BRAIN; MOOD;
NEUROGENESIS; SEIZURES
AB While conventional antidepressants benefit many patients with major depressive disorder (MDD), as much as eight to 12 weeks can elapse before significant improvements in depressive symptoms are seen. Treatments that act more rapidly in MDD are urgently needed. Sleep deprivation (SD) has been shown to produce a rapid antidepressant response within one day in 50-60% of patients with MDD; thus, identifying its antidepressant mechanism may contribute to the development of antidepressants that act more rapidly. The present study evaluated the effects of 39 h of SD on mood, as well as on plasma levels of brain derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) in patients with MDD. After a drug-free period of at least two weeks, 11 patients (6 males, 5 females; ages 25-62) who met DSM-IV criteria for MDD underwent total SD. Plasma samples for BDNF and VEGF assays were collected on Days 1 (baseline) and 2. The six-item Hamilton Rating Scale for Depression (HAMD-6) was the primary outcome measure. HAMD-6 scores decreased significantly after SD (Day 2). SD was negatively correlated with change in HAMD-6 score and change in VEGF levels, indicating that as depression scores decreased following SD, VEGF plasma levels increased. In contrast, SD did not alter plasma BDNF concentrations, nor was an association found between BDNF levels and clinical improvement on the HAMD-6. These results suggest that SD is associated with mood-related changes in plasma VEGF levels, but not plasma BDNF levels. Further studies using larger sample sizes are needed to confirm these preliminary findings. Published by Elsevier Inc.
C1 [Ibrahim, Lobna; Duncan, Wallace; Luckenbaugh, David A.; Machado-Vieira, Rodrigo; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Div Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Ibrahim, Lobna; Duncan, Wallace; Luckenbaugh, David A.; Yuan, Peixiong; Machado-Vieira, Rodrigo; Zarate, Carlos A., Jr.] Dept Hlth & Human Serv, Bethesda, MD USA.
[Ibrahim, Lobna; Duncan, Wallace; Luckenbaugh, David A.; Yuan, Peixiong; Zarate, Carlos A., Jr.] NIMH, Mood & Anxiety Disorders Program, Div Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Machado-Vieira, Rodrigo] Univ Sao Paulo, Inst Psychiat, LIM 27, BR-05508 Sao Paulo, Brazil.
[Machado-Vieira, Rodrigo] Univ Sao Paulo, Dept Psychiat, LIM 27, BR-05508 Sao Paulo, Brazil.
RP Zarate, CA (reprint author), CRC, 10 Ctr Dr,Unit 7 SE,Room 7-3445, Bethesda, MD 20892 USA.
EM ibrahiml@mail.nih.gov; wduncan@mail.nih.gov; luckenbd@mail.nih.gov;
PeixiongYuan@mail.nih.gov; machadovieirar@gmail.com;
zaratec@mail.nih.gov
RI MACHADO-VIEIRA, RODRIGO/D-8293-2012
OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190
FU National Institute of Mental Health, National Institutes of Health, and
Department of Health & Human Services (IRP-NIMH-NIH-DHHS); 7SE research
unit and research staff
FX This study was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health, and
Department of Health & Human Services (IRP-NIMH-NIH-DHHS).; We thank the
7SE research unit and research staff for their support, and loline
Henter for her outstanding editorial assistance in the preparation of
this manuscript.
NR 35
TC 20
Z9 21
U1 1
U2 9
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0361-9230
J9 BRAIN RES BULL
JI Brain Res. Bull.
PD AUG 10
PY 2011
VL 86
IS 1-2
BP 129
EP 133
DI 10.1016/j.brainresbull.2011.06.003
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 820DW
UT WOS:000294886700018
PM 21704134
ER
PT J
AU Niedzwiecki, D
Bertagnolli, MM
Warren, RS
Compton, CC
Kemeny, NE
Benson, AB
Eckhardt, SG
Alberts, S
Porjosh, GN
Kerr, DJ
Fields, A
Rougier, P
Pipas, JM
Schwartz, JH
Atkins, J
O'Rourke, M
Perry, MC
Goldberg, RM
Mayer, RJ
Colacchio, TA
AF Niedzwiecki, Donna
Bertagnolli, Monica M.
Warren, Robert S.
Compton, Carolyn C.
Kemeny, Nancy E.
Benson, Al Bowen, III
Eckhardt, S. Gail
Alberts, Steven
Porjosh, Gity N.
Kerr, David J.
Fields, Anthony
Rougier, Philippe
Pipas, J. Marc
Schwartz, Joel H.
Atkins, James
O'Rourke, Mark
Perry, Michael C.
Goldberg, Richard M.
Mayer, Robert J.
Colacchio, Thomas A.
TI Documenting the Natural History of Patients With Resected Stage II
Adenocarcinoma of the Colon After Random Assignment to Adjuvant
Treatment With Edrecolomab or Observation: Results From CALGB 9581
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID COLORECTAL-CANCER; MONOCLONAL-ANTIBODIES; FOLINIC ACID; DOSE LEUCOVORIN;
COMPETING RISK; FLUOROURACIL; THERAPY; SURVIVAL; TRIAL; CHEMOTHERAPY
AB Purpose
We conducted a randomized trial comparing adjuvant treatment with edrecolomab versus observation in patients with resected, low-risk, stage II colon cancer. This study also prospectively studied patient-and tumor-specific markers of treatment outcome.
Patients and Methods
After surgical resection, patients with stage II colon cancer were randomly assigned to either five infusions of edrecolomab at 28-day intervals or observation without adjuvant therapy.
Results
Final accrual included 1,738 patients; 865 patients received edrecolomab, and 873 patients were observed without adjuvant treatment. Median follow-up time was 7.9 years. There were no significant outcome differences between study arms (overall survival [OS], P = .71; disease-free survival, P = .64). The combined 5-year all-cause OS was 0.86 (95% CI, 0.84 to 0.88), and the combined 5-year disease-specific OS was 0.93 (95% CI, 0.91 to 0.94). The relationships between demographic and histopathologic factors and survival differed for all-cause and disease-specific survival outcomes, but no combined prognostic factor model was found to adequately classify patients at higher risk of recurrence or death as a result of colon cancer.
Conclusion
Edrecolomab did not prolong survival. Consequently, this large study with a long duration of follow-up provided unique data concerning the natural history of resected stage II colon cancer. Prognostic factors identified in previous retrospective and pooled analyses were associated with survival outcomes in this stage II patient cohort. Results from ongoing molecular marker studies may enhance our ability to determine the risk profile of these patients.
C1 [Niedzwiecki, Donna] Duke Univ Med Ctr, Canc & Leukemia Grp Stat Ctr B, Durham, NC 27705 USA.
SE Canc Control Consortium, Goldsboro, NC USA.
Univ N Carolina, Chapel Hill, NC USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
Eastern Cooperat Oncol Grp, Boston, MA USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
N Shore Canc Ctr, Danvers, MA USA.
Univ Calif San Francisco, San Francisco, CA 94143 USA.
NCI, Bethesda, MD 20892 USA.
Natl Canc Inst Expanded Participat Project, Rockville, MD USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
SW Oncol Grp, San Antonio, TX USA.
N Cent Canc Treatment Grp, Rochester, MN USA.
Inova Res Ctr, Falls Church, VA USA.
Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA.
Canc Ctr Carolinas, Greenville, SC USA.
Univ Missouri Ellis Fischel Canc Ctr, Columbia, MO USA.
Canc Res Clin Trials Unit, Birmingham, W Midlands, England.
Oxford Canc Trials Off, Oxford, England.
Natl Canc Inst Canada Clin Trials Grp, Kingston, ON, Canada.
European Org Res Treatment Canc, Brussels, Belgium.
Hop Europeen Georges Pompidou, Paris, France.
RP Niedzwiecki, D (reprint author), Duke Univ Med Ctr, Canc & Leukemia Grp Stat Ctr B, Hock Plaza,2424 Erwin Rd,Room 8040, Durham, NC 27705 USA.
EM niedz001@mc.duke.edu
RI Goldberg , Richard/M-1311-2013
FU Centocor; GlaxoSmithKline
FX Research Funding: David J. Kerr, Centocor; Anthony Fields,
GlaxoSmithKline
NR 44
TC 25
Z9 27
U1 0
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD AUG 10
PY 2011
VL 29
IS 23
BP 3146
EP 3152
DI 10.1200/JCO.2010.32.5357
PG 7
WC Oncology
SC Oncology
GA 804BJ
UT WOS:000293628400015
PM 21747085
ER
PT J
AU Bertagnolli, MM
Redston, M
Compton, CC
Niedzwiecki, D
Mayer, RJ
Goldberg, RM
Colacchio, TA
Saltz, LB
Warren, RS
AF Bertagnolli, Monica M.
Redston, Mark
Compton, Carolyn C.
Niedzwiecki, Donna
Mayer, Robert J.
Goldberg, Richard M.
Colacchio, Thomas A.
Saltz, Leonard B.
Warren, Robert S.
TI Microsatellite Instability and Loss of Heterozygosity at Chromosomal
Location 18q: Prospective Evaluation of Biomarkers for Stages II and III
Colon Cancer-A Study of CALGB 9581 and 89803
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID COLORECTAL-CANCER; ALLELIC LOSS; ADJUVANT CHEMOTHERAPY; GENETIC
ALTERATIONS; PROGNOSTIC MARKER; FLUOROURACIL; SURVIVAL; CARCINOMA;
TUMOR; LEUCOVORIN
AB Purpose
Colorectal cancer (CRC) develops as a result of a series of accumulated genomic changes that produce oncogene activation and tumor suppressor gene loss. These characteristics may classify CRC into subsets of distinct clinical behaviors.
Patients and Methods
We studied two of these genomic defects-mismatch repair deficiency (MMR-D) and loss of heterozygosity at chromosomal location 18q (18qLOH)-in patients enrolled onto two phase III cooperative group trials for treatment of potentially curable colon cancer. These trials included prospective secondary analyses to determine the relationship between these markers and treatment outcome. A total of 1,852 patients were tested for MMR status and 955 (excluding patients with MMR-D tumors) for 18qLOH.
Results
Compared with stage III, more stage II tumors were MMR-D (21.3% v 14.4%; P < .001) and were intact at 18q (24.2% v 15.1%; P = .001). For the combined cohort, patients with MMR-D tumors had better 5-year disease-free survival (DFS; 0.76 v 0.67; P < .001) and overall survival (OS; 0.81 v 0.78; P = .029) than those with MMR intact (MMR-I) tumors. Among patients with MMR-I tumors, the status of 18q did not affect outcome, with 5-year values for patients with 18q intact versus 18qLOH tumors of 0.74 versus 0.65 (P = .18) for DFS and 0.81 versus 0.77 (P = .18) for OS.
Conclusion
We conclude that MMR-D tumor status, but not the presence of 18qLOH, has prognostic value for stages II and III colon cancer.
C1 [Bertagnolli, Monica M.; Redston, Mark] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Bertagnolli, Monica M.; Mayer, Robert J.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Niedzwiecki, Donna] Duke Univ Med Ctr, Canc & Leukemia Grp Stat Ctr B, Durham, NC USA.
[Goldberg, Richard M.] Univ N Carolina, Chapel Hill, NC USA.
[Compton, Carolyn C.] NCI, Bethesda, MD 20892 USA.
[Colacchio, Thomas A.] Dartmouth Hitchcock Med Ctr, Hanover, NH USA.
[Saltz, Leonard B.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Warren, Robert S.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
RP Bertagnolli, MM (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
EM mbertagnolli@partners.org
RI Goldberg , Richard/M-1311-2013
FU National Cancer Institute, Bethesda, MD [CA31946, CA33601]
FX Supported in part by Grants No. CA31946 from the National Cancer
Institute, Bethesda, MD, to CALGB (M.M.B.) and No. CA33601 to the CALGB
Statistical Center (Daniel J. Sargent, Group Statistician and principal
investigator).
NR 35
TC 57
Z9 57
U1 1
U2 6
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD AUG 10
PY 2011
VL 29
IS 23
BP 3153
EP 3162
DI 10.1200/JCO.2010.33.0092
PG 10
WC Oncology
SC Oncology
GA 804BJ
UT WOS:000293628400016
PM 21747089
ER
PT J
AU Bande, RJ
Appella, DH
Trenkle, WC
AF Bande, Robert J.
Appella, Daniel H.
Trenkle, William C.
TI A one-pot preparation of N-2-mercaptobenzoyl-amino amides
SO TETRAHEDRON LETTERS
LA English
DT Article
DE HBTU; Amide formation; Thioester; Topical microbicide
ID HIV NUCLEOCAPSID PROTEIN; ACYL TRANSFER; INHIBITORS; INFECTIVITY;
THIOESTERS; RESIDUES; AGENTS; NCP7
AB The HIV-1 nucleocapsid (NCp7), structurally defined by zinc-binding domains, participates in crucial stages of the HIV-1 lifecycle and is mutationally nonpermissive, making it an attractive anti-HIV target. Mode of action studies have shown that the secondary structure and activity of NCp7 can be disrupted by acyl transfer from N-2-mercaptobenzoyl-amino amides. We have developed an improved one-pot reaction that affords N-2-mercaptobenzoyl-amino acids on multi-gram scales. This synthetic route allows for rapid modular construction and has greatly expanded the scope of easily accessible potential NCp7 inhibitors. Published by Elsevier Ltd.
C1 [Bande, Robert J.; Appella, Daniel H.; Trenkle, William C.] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Trenkle, WC (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA.
EM wtrenkle@niddk.nih.gov
FU NIH, National Institute of Diabetes and Digestive and Kidney Diseases
FX This research was supported in part by the Intramural Research Program
of the NIH, National Institute of Diabetes and Digestive and Kidney
Diseases. We thank Ettore Appella, and Lisa M. Miller Jenkins (NIH, NCI)
and Hans F. Luecke and Dongwook Kang (NIH, NIDDK) for helpful
discussion. We thank Noel Whittaker for able assistance with Mass
Spectral Analyses.
NR 18
TC 1
Z9 1
U1 2
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0040-4039
J9 TETRAHEDRON LETT
JI Tetrahedron Lett.
PD AUG 10
PY 2011
VL 52
IS 32
BP 4103
EP 4105
DI 10.1016/j.tetlet.2011.05.115
PG 3
WC Chemistry, Organic
SC Chemistry
GA 799XW
UT WOS:000293321000009
ER
PT J
AU Devaney, SA
Palomaki, GE
Scott, JA
Bianchi, DW
AF Devaney, Stephanie A.
Palomaki, Glenn E.
Scott, Joan A.
Bianchi, Diana W.
TI Noninvasive Fetal Sex Determination Using Cell-Free Fetal DNA A
Systematic Review and Meta-analysis
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Review
ID REAL-TIME PCR; POLYMERASE-CHAIN-REACTION; CHROMOSOME-SPECIFIC DNA;
MATERNAL PLASMA; GENDER DETERMINATION; PRENATAL-DIAGNOSIS;
PREGNANT-WOMEN; QUANTITATIVE-ANALYSIS; SERUM; BLOOD
AB Context Noninvasive prenatal determination of fetal sex using cell-free fetal DNA provides an alternative to invasive techniques for some heritable disorders. In some countries this testing has transitioned to clinical care, despite the absence of a formal assessment of performance.
Objective To document overall test performance of noninvasive fetal sex determination using cell-free fetal DNA and to identify variables that affect performance.
Data Sources Systematic review and meta-analysis with search of PubMed (January 1, 1997-April 17, 2011) to identify English-language human studies reporting primary data. References from review articles were also searched.
Study Selection and Data Extraction Abstracts were read independently to identify studies reporting primary data suitable for analysis. Covariates included publication year, sample type, DNA amplification methodology, Y chromosome sequence, and gestational age. Data were independently extracted by 2 reviewers.
Results From 57 selected studies, 80 data sets (representing 3524 male-bearing pregnancies and 3017 female-bearing pregnancies) were analyzed. Overall performance of the test to detect Y chromosome sequences had the following characteristics: sensitivity, 95.4% (95% confidence interval [CI], 94.7%-96.1%) and specificity, 98.6% (95% CI, 98.1%-99.0%); diagnostic odds ratio (OR), 885; positive predictive value, 98.8%; negative predictive value, 94.8%; area under curve (AUC), 0.993 (95% CI, 0.989-0.995), with significant interstudy heterogeneity. DNA methodology and gestational age had the largest effects on test performance. Methodology test characteristics were AUC, 0.988 (95% CI, 0.979-0.993) for polymerase chain reaction (PCR) and AUC, 0.996 (95% CI, 0.993-0.998) for real-time quantitative PCR (RTQ-PCR) (P=.02). Gestational age test characteristics were AUC, 0.989 (95% CI, 0.965-0.998) (<7 weeks); AUC, 0.994 (95% CI, 0.987-0.997) (7-12 weeks); AUC, 0.992 (95% CI, 0.983-0.996) (13-20 weeks); and AUC, 0.998 (95% CI, 0.990-0.999) (>20 weeks) (P=.02 for comparison of diagnostic ORs across age ranges). RTQ-PCR (sensitivity, 96.0%; specificity, 99.0%) outperformed conventional PCR (sensitivity, 94.0%; specificity, 97.3%). Testing after 20 weeks (sensitivity, 99.0%; specificity, 99.6%) outperformed testing prior to 7 weeks (sensitivity, 74.5%; specificity, 99.1%), testing at 7 through 12 weeks (sensitivity, 94.8%; specificity, 98.9%), and 13 through 20 weeks (sensitivity, 95.5%; specificity, 99.1%).
Conclusions Despite interstudy variability, performance was high using maternal blood. Sensitivity and specificity for detection of Y chromosome sequences was greatest using RTQ-PCR after 20 weeks' gestation. Tests using urine and tests performed before 7 weeks' gestation were unreliable. JAMA. 2011;306(6):627-636 www.jama.com
C1 [Devaney, Stephanie A.] NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Devaney, Stephanie A.; Scott, Joan A.] Johns Hopkins Univ, Genet & Publ Policy Ctr, Washington, DC USA.
[Palomaki, Glenn E.] Brown Univ, Women & Infants Hosp, Alpert Med Sch, Providence, RI USA.
[Scott, Joan A.] Natl Coalit Hlth Profess Educ Genet, Lutherville Timonium, MD USA.
[Bianchi, Diana W.] Tufts Med Ctr, Mother Infant Res Inst, Boston, MA USA.
[Bianchi, Diana W.] Floating Hosp Children, Div Genet, Boston, MA USA.
RP Devaney, SA (reprint author), NIH, Dept Hlth & Human Serv, 1 Ctr Dr,Room 103, Bethesda, MD 20892 USA.
EM stephanie.devaney@nih.gov
FU National Human Genome Research Institute [1R21HG004865-02]; Sequenom Inc
FX This study was supported by the National Human Genome Research Institute
(1R21HG004865-02).; All authors have completed and submitted the ICMJE
Form for Disclosure of Potential Conflicts of Interest. Dr Palomaki
reported having a sponsored research agreement with Sequenom Inc to
study circulating cell-free fetal DNA. Dr Bianchi reported serving as a
member of the scientific and clinical advisory boards of Verinata Health
Inc, an early-stage biotechnology company; she receives honoraria and
holds stock options in this company. No other authors reported
disclosures.
NR 91
TC 102
Z9 105
U1 1
U2 24
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD AUG 10
PY 2011
VL 306
IS 6
BP 627
EP 636
DI 10.1001/jama.2011.1114
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 804XD
UT WOS:000293687300024
PM 21828326
ER
PT J
AU Hong, S
Jhou, TC
Smith, M
Saleem, KS
Hikosaka, O
AF Hong, Simon
Jhou, Thomas C.
Smith, Mitchell
Saleem, Kadharbatcha S.
Hikosaka, Okihide
TI Negative Reward Signals from the Lateral Habenula to Dopamine Neurons
Are Mediated by Rostromedial Tegmental Nucleus in Primates
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID DORSAL RAPHE NUCLEUS; SUBSTANTIA-NIGRA; GABAERGIC NEURONS; RAT; AREA;
MIDBRAIN; STIMULATION; CONNECTIONS; PROJECTIONS; AFFERENT
AB Lateral habenula (LHb) neurons signal negative "reward-prediction errors" and inhibit midbrain dopamine (DA) neurons. Yet LHb neurons are largely glutamatergic, indicating that this inhibition may occur through an intermediate structure. Recent studies in rats have suggested a candidate for this role, the GABAergic rostromedial tegmental nucleus (RMTg), but this neural pathway has not yet been tested directly. We now show using electrophysiology and anatomic tracing that (1) the monkey has an inhibitory structure similar to the rat RMTg; (2) RMTg neurons receive excitatory input from the LHb, exhibit negative reward-prediction errors, and send axonal projections near DA soma; and (3) stimulating this structure inhibits DA neurons. Surprisingly, some RMTg neurons responded to reward cues earlier than the LHb, and carry "state-value" signals not found in DA neurons. Thus, our data suggest that the RMTg translates LHb reward-prediction errors (negative) into DA reward-prediction errors (positive), while transmitting additional motivational signals to non-DA networks.
C1 [Hong, Simon; Smith, Mitchell; Hikosaka, Okihide] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
[Saleem, Kadharbatcha S.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
[Jhou, Thomas C.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA.
RP Hong, S (reprint author), NEI, Sensorimotor Res Lab, NIH, 49 Convent Dr, Bethesda, MD 20892 USA.
EM hongy@nei.nih.gov
OI Saleem, Kadharbatcha S/0000-0002-4450-9234
FU National Eye Institute
FX This work was supported by the intramural research program of the
National Eye Institute. We are grateful to E. S. Bromberg-Martin, H.
Kim, Y. Tachibana, S. Yamamoto, and M. Yasuda for helpful comments, and
D. Parker, B. Nagy, G. Tansey, J. W. McClurkin, A. M. Nichols, and T. W.
Ruffner for technical assistance.
NR 32
TC 130
Z9 133
U1 1
U2 8
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD AUG 10
PY 2011
VL 31
IS 32
BP 11457
EP 11471
DI 10.1523/JNEUROSCI.1384-11.2011
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA 805NV
UT WOS:000293735900005
PM 21832176
ER
PT J
AU Marenco, S
Geramita, M
van der Veen, JW
Barnett, AS
Kolachana, B
Shen, J
Weinberger, DR
Law, AJ
AF Marenco, Stefano
Geramita, Matthew
van der Veen, Jan Willem
Barnett, Alan S.
Kolachana, Bhaskar
Shen, Jun
Weinberger, Daniel R.
Law, Amanda J.
TI Genetic Association of ErbB4 and Human Cortical GABA Levels In Vivo
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID GAMMA-AMINOBUTYRIC-ACID; MAGNETIC-RESONANCE SPECTROSCOPY; T-2
RELAXATION; SCHIZOPHRENIA; RECEPTOR; CORTEX; BRAIN; EXPRESSION;
GLUTAMATE; VARIANTS
AB NRG1-ErbB4 signaling controls inhibitory circuit development in the mammalian cortex through ErbB4-dependent regulation of GABAergic interneuron connectivity. Common genetic variation in ErbB4 (rs7598440) has been associated with ErbB4 messenger RNA levels in the human cortex and risk for schizophrenia. Recent work demonstrates that Erbb4 is expressed exclusively on inhibitory interneurons, where its presence on parvalbumin-positive cells mediates the effects of NRG1 on inhibitory circuit formation in the cortex. We therefore hypothesized that genetic variation in ErbB4 at rs7598440 would impact indices of GABA concentration in the human cortex. We tested this hypothesis in 116 healthy volunteers by measuring GABA and GLX (glutamate + glutamine) with proton magnetic resonance spectroscopy in the dorsal anterior cingulate gyrus. ErbB4 rs7598440 genotype significantly predicted cortical GABA concentration (p = 0.014), but not GLX (p = 0.51), with A allele carriers having higher GABA as predicted by the allelic impact on ErbB4 expression. These data establish an association of ErbB4 and GABA in human brain and have implications for understanding the pathogenesis of schizophrenia and other psychiatric disorders.
C1 [Marenco, Stefano; Geramita, Matthew; Barnett, Alan S.; Kolachana, Bhaskar; Weinberger, Daniel R.; Law, Amanda J.] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Intramural Res Program,NIH, Bethesda, MD 20892 USA.
[Marenco, Stefano; Geramita, Matthew; Barnett, Alan S.] NIMH, Unit Multimodal Imaging Genet, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Marenco, S (reprint author), NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Intramural Res Program,NIH, 10 Ctr Dr,Bldg 10,Room 3C103, Bethesda, MD 20892 USA.
EM marencos@mail.nih.gov
RI Law, Amanda/G-6372-2012; Marenco, Stefano/A-2409-2008;
OI Marenco, Stefano/0000-0002-2488-2365; Law, Amanda/0000-0002-2574-1564
FU NIMH
FX This work was funded entirely from the NIMH Intramural Research Program.
We thank Antonina A. Savostyanova for help in collecting and organizing
the data and running preliminary analyses.
NR 33
TC 18
Z9 18
U1 0
U2 2
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD AUG 10
PY 2011
VL 31
IS 32
BP 11628
EP 11632
DI 10.1523/JNEUROSCI.1529-11.2011
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 805NV
UT WOS:000293735900021
PM 21832192
ER
PT J
AU Farber, GK
Weiss, L
AF Farber, Gregory K.
Weiss, Linda
TI Core Facilities: Maximizing the Return on Investment
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
AB To conduct high-quality state-of-the-art research, clinical and translational scientists need access to specialized core facilities and appropriately trained staff. In this time of economic constraints and increasing research costs, organized and efficient core facilities are essential for researchers who seek to investigate complex translational research questions. Here, we describe efforts at the U.S. National Institutes of Health and academic medical centers to enhance the utility of cores.
C1 [Farber, Gregory K.] Natl Ctr Res Resources, Off Extramural Act, NIH, Bethesda, MD 20892 USA.
[Weiss, Linda] NCI, Off Canc Ctr, NIH, Bethesda, MD 20892 USA.
RP Farber, GK (reprint author), Natl Ctr Res Resources, Off Extramural Act, NIH, 6701 Democracy Blvd,Room 1001, Bethesda, MD 20892 USA.
EM farberg@mail.nih.gov
FU Intramural NIH HHS [Z99 MH999999]
NR 8
TC 2
Z9 2
U1 0
U2 7
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD AUG 10
PY 2011
VL 3
IS 95
AR 95cm21
DI 10.1126/scitranslmed.3002421
PG 3
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 805OU
UT WOS:000293739300001
PM 21832235
ER
PT J
AU Hurley, JH
AF Hurley, James H.
TI Nipped in the Bud: How the AMSH MIT Domain Helps Deubiquitinate
Lysosome-Bound Cargo
SO STRUCTURE
LA English
DT Editorial Material
ID ESCRT-III RECOGNITION; STRUCTURAL BASIS; VPS4; CHAINS
C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Hurley, JH (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM hurley@helix.nih.gov
FU Intramural NIH HHS [ZIA DK036123-05, ZIA DK036126-05]
NR 10
TC 2
Z9 2
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0969-2126
J9 STRUCTURE
JI Structure
PD AUG 10
PY 2011
VL 19
IS 8
BP 1033
EP 1035
DI 10.1016/j.str.2011.07.002
PG 3
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 806PB
UT WOS:000293819000002
PM 21827939
ER
PT J
AU Srinivasan, P
Beatty, WL
Diouf, A
Herrera, R
Ambroggio, X
Moch, JK
Tyler, JS
Narum, DL
Pierce, SK
Boothroyd, JC
Haynes, JD
Miller, LH
AF Srinivasan, Prakash
Beatty, Wandy L.
Diouf, Ababacar
Herrera, Raul
Ambroggio, Xavier
Moch, J. Kathleen
Tyler, Jessica S.
Narum, David L.
Pierce, Susan K.
Boothroyd, John C.
Haynes, J. David
Miller, Louis H.
TI Binding of Plasmodium merozoite proteins RON2 and AMA1 triggers
commitment to invasion
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE AMA1-RON2; malaria; moving junction
ID APICAL MEMBRANE ANTIGEN-1; MALARIA VACCINE CANDIDATE; TOXOPLASMA-GONDII;
ERYTHROCYTE INVASION; PARASITOPHOROUS VACUOLE; APICOMPLEXAN PARASITES;
FALCIPARUM MEROZOITES; INHIBITORY ANTIBODY; ANONYMOUS PROTEIN; MOVING
JUNCTION
AB The commitment of Plasmodium merozoites to invade red blood cells (RBCs) is marked by the formation of a junction between the merozoite and the RBC and the coordinated induction of the parasitophorous vacuole. Despite its importance, the molecular events underlying the parasite's commitment to invasion are not well understood. Here we show that the interaction of two parasite proteins, RON2 and AMA1, known to be critical for invasion, is essential to trigger junction formation. Using antibodies (Abs) that bind near the hydrophobic pocket of AMA1 and AMA1 mutated in the pocket, we identified RON2's binding site on AMA1. Abs specific for the AMA1 pocket blocked junction formation and the induction of the parasitophorous vacuole. We also identified the critical residues in the RON2 peptide (previously shown to bind AMA1) that are required for binding to the AMA1 pocket, namely, two conserved, disulfide-linked cysteines. The RON2 peptide blocked junction formation but, unlike the AMA1-specific Ab, did not block formation of the parasitophorous vacuole, indicating that formation of the junction and parasitophorous vacuole are molecularly distinct steps in the invasion process. Collectively, these results identify the binding of RON2 to the hydrophobic pocket of AMA1 as the step that commits Plasmodium merozoites to RBC invasion and point to RON2 as a potential vaccine candidate.
C1 [Srinivasan, Prakash; Diouf, Ababacar; Miller, Louis H.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Herrera, Raul; Narum, David L.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD 20852 USA.
[Pierce, Susan K.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Beatty, Wandy L.] Washington Univ, Dept Mol Microbiol, Sch Med, St Louis, MO 63130 USA.
[Ambroggio, Xavier] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, Bethesda, MD 20892 USA.
[Moch, J. Kathleen; Haynes, J. David] Walter Reed Army Inst Res, Div Malaria Vaccine Dev, Silver Spring, MD 20910 USA.
[Tyler, Jessica S.; Boothroyd, John C.] Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA 94305 USA.
RP Srinivasan, P (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
EM srinivasanp@niaid.nih.gov; lmiller@niaid.nih.gov
OI Miller, Louis/0000-0003-3420-1284
FU National Institutes of Health
FX We thank Drs. Robin F. Anders, Jean-Francois Dubremetz, and Takafumi
Tsuboi for antibodies 1F9 (AMA1), 24C6 (RON4), and RON2, respectively;
Lydia Kibiuk for help with art illustration; and Dr. Susham Ingavale for
critical reading of the manuscript. This work was supported by the
National Institutes of Health Intramural Research Program.
NR 41
TC 104
Z9 105
U1 1
U2 12
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD AUG 9
PY 2011
VL 108
IS 32
BP 13275
EP 13280
DI 10.1073/pnas.1110303108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 804YK
UT WOS:000293691400063
PM 21788485
ER
PT J
AU Lucia, MB
Anu, R
Handley, M
Gillet, JP
Wu, CP
De Donatis, GM
Cauda, R
Gottesman, MM
AF Lucia, M. B.
Anu, R.
Handley, M.
Gillet, J-P
Wu, C-P
De Donatis, G. M.
Cauda, R.
Gottesman, M. M.
TI Exposure to HIV-protease inhibitors selects for increased expression of
P-glycoprotein (ABCB1) in Kaposi's sarcoma cells
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE P-glycoprotein; ABCB1; Kaposi's sarcoma; HIV-protease inhibitors;
multidrug resistance
ID ACTIVE ANTIRETROVIRAL THERAPY; AIDS-RELATED MALIGNANCIES;
MULTIDRUG-RESISTANCE; CLINICAL-RESPONSE; TARGETED THERAPY; CANCER;
TRANSPORTERS; LOPINAVIR; LINES; DOXORUBICIN
AB BACKGROUND: Given that HIV-protease inhibitors (HIV-PIs) are substrates/inhibitors of the multidrug transporter ABCB1, can induce ABCB1 expression, and are used in combination with doxorubicin for AIDS-Kaposi's Sarcoma (KS) treatment, the role that ABCB1 plays in mediating multidrug resistance (MDR) in a fully transformed KS cell line (SLK) was explored.
METHODS: The KS cells were exposed to both acute and chronic treatments of physiological concentrations of different HIV-PIs (indinavir, nelfinavir, atazanavir, ritonavir, or lopinavir), alone or together with doxorubicin. The ABCB1 mRNA and protein expression levels were then assessed by qRT-PCR and western blotting, flow cytometry, and immunofluorescence.
RESULTS: Chronic treatment of SLK cells with one of the five HIV-PIs alone or together resulted in increased resistance to doxorubicin. Co-treatment with one of the HIV-PIs in combination with doxorubicin resulted in a synergistic increase in resistance to doxorubicin, and the degree of resistance was found to correlate with the expression of ABCB1. The SLK cells were also revealed to be cross-resistant to the structurally unrelated drug paclitaxel.
CONCLUSION: These studies suggest that ABCB1 is primarily responsible for mediating MDR in SLK cells selected with either HIV-PIs alone or in combination with doxorubicin. Therefore, the roles that ABCB1 and drug cocktails play in mediating MDR in KS in vivo should be evaluated. British Journal of Cancer (2011) 105, 513-522. doi:10.1038/bjc.2011.275 www.bjcancer.com (C) 2011 Cancer Research UK
C1 [Lucia, M. B.; Anu, R.; Handley, M.; Gillet, J-P; Wu, C-P; De Donatis, G. M.; Gottesman, M. M.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Lucia, M. B.; Cauda, R.] Catholic Univ, Dept Infect Dis, Rome, Italy.
RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 2108, Bethesda, MD 20892 USA.
EM mgottesman@nih.gov
RI gillet, jean-pierre/A-3714-2012;
OI CAUDA, Roberto/0000-0002-1498-4229
FU National Institutes of Health, National Cancer Institute; FIRB:
'Costruzione di un laboratorio nazionale per lo studio
dell'antibiotico-resistenza'
FX This study was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute. MBL was in
part supported by a grant from FIRB: 'Costruzione di un laboratorio
nazionale per lo studio dell'antibiotico-resistenza' (Resp. Professor A
Cassone). We thank Mr George Leiman for editorial assistance.
NR 49
TC 3
Z9 3
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD AUG 9
PY 2011
VL 105
IS 4
BP 513
EP 522
DI 10.1038/bjc.2011.275
PG 10
WC Oncology
SC Oncology
GA 806DB
UT WOS:000293784400008
PM 21829205
ER
PT J
AU Zhang, MZ
Zhang, RP
He, MG
Liang, WL
Li, XF
She, LB
Yang, YL
MacKenzie, G
Silver, JD
Ellwein, L
Moore, B
Congdon, N
AF Zhang, Mingzhi
Zhang, Riping
He, Mingguang
Liang, Wanling
Li, Xiaofeng
She, Lingbing
Yang, Yunli
MacKenzie, Graeme
Silver, Joshua D.
Ellwein, Leon
Moore, Bruce
Congdon, Nathan
TI Self correction of refractive error among young people in rural China:
results of cross sectional investigation
SO BRITISH MEDICAL JOURNAL
LA English
DT Article
ID LOW-RESOURCE COUNTRIES; VISUAL IMPAIRMENT; SCHOOL-CHILDREN; SECONDARY
SCHOOLCHILDREN; SOUTHERN CHINA; X-PRES; POPULATION; TEACHERS; DISTRICT;
STUDENTS
AB Objective To compare outcomes between adjustable spectacles and conventional methods for refraction in young people.
Design Cross sectional study.
Setting Rural southern China.
Participants 648 young people aged 12-18 (mean 14.9 (SD 0.98)), with uncorrected visual acuity <= 6/12 in either eye.
Interventions All participants underwent self refraction without cycloplegia (paralysis of near focusing ability with topical eye drops), automated refraction without cycloplegia, and subjective refraction by an ophthalmologist with cycloplegia.
Main outcome measures Uncorrected and corrected vision, improvement of vision (lines on a chart), and refractive error.
Results Among the participants, 59% (384) were girls, 44% (288) wore spectacles, and 61% (393/648) had 2.00 dioptres or more of myopia in the right eye. All completed self refraction. The proportion with visual acuity >= 6/7.5 in the better eye was 5.2% (95% confidence interval 3.6% to 6.9%) for uncorrected vision, 30.2% (25.7% to 34.8%) for currently worn spectacles, 96.9% (95.5% to 98.3%) for self refraction, 98.4% (97.4% to 99.5%) for automated refraction, and 99.1% (98.3% to 99.9%) for subjective refraction (P=0.033 for self refraction v automated refraction, P=0.001 for self refraction v subjective refraction). Improvements over uncorrected vision in the better eye with self refraction and subjective refraction were within one line on the eye chart in 98% of participants. In logistic regression models, failure to achieve maximum recorded visual acuity of 6/7.5 in right eyes with self refraction was associated with greater absolute value of myopia/hyperopia (P<0.001), greater astigmatism (P=0.001), and not having previously worn spectacles (P=0.002), but not age or sex. Significant inaccuracies in power (>= 1.00 dioptre) were less common in right eyes with self refraction than with automated refraction (5% v 11%, P<0.001).
Conclusions Though visual acuity was slightly worse with self refraction than automated or subjective refraction, acuity was excellent in nearly all these young people with inadequately corrected refractive error at baseline. Inaccurate power was less common with self refraction than automated refraction. Self refraction could decrease the requirement for scarce trained personnel, expensive devices, and cycloplegia in children's vision programmes in rural China.
C1 [He, Mingguang; Congdon, Nathan] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab, Ophthalmol Grp, Guangzhou 510060, Guangdong, Peoples R China.
[He, Mingguang; Congdon, Nathan] Sun Yat Sen Univ, Div Prevent Ophthalmol, Guangzhou 510060, Guangdong, Peoples R China.
[Zhang, Mingzhi] Joint Shantou Int Eye Ctr, Refract Serv, Shantou, Peoples R China.
[MacKenzie, Graeme] Adlens, Oxford OX2 8AH, England.
[MacKenzie, Graeme] John Radcliffe Hosp, Nuffield Lab Ophthalmol, Oxford OX3 9DU, England.
[Silver, Joshua D.] Univ Oxford St Catherines Coll, Ctr Vis Dev World, Oxford OX1 3UJ, England.
[Ellwein, Leon] NEI, Bethesda, MD 20892 USA.
[Moore, Bruce] New England Coll Optometry, Boston, MA USA.
RP Congdon, N (reprint author), Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab, Ophthalmol Grp, 54 Xianlie S Rd, Guangzhou 510060, Guangdong, Peoples R China.
EM ncongdon1@gmail.com
OI He, Mingguang/0000-0002-6912-2810
FU Imperial College of Science, Technology and Medicine under the World
Bank
FX This study was funded by grant to the Nuffield Laboratory of
Ophthalmology (University of Oxford) from the Partnership for Child
Development, (Imperial College of Science, Technology and Medicine)
under the World Bank's FY2009 Development Grant Facility (DGF) Window 1.
The adjustable spectacles used in this study were provided free of
charge by Adaptive Eyecare. The study sponsor played no role in study
design and the collection, analysis, and interpretation of data and the
writing of the article and the decision to submit it for publication.
NR 33
TC 8
Z9 9
U1 0
U2 14
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0959-535X
J9 BRIT MED J
JI Br. Med. J.
PD AUG 9
PY 2011
VL 343
AR d4767
DI 10.1136/bmj.d4767
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 808CX
UT WOS:000293954000001
PM 21828207
ER
PT J
AU Decker, M
Jaensch, S
Pozniakovsky, A
Zinke, A
O'Connell, KF
Zachariae, W
Myers, E
Hyman, AA
AF Decker, Markus
Jaensch, Steffen
Pozniakovsky, Andrei
Zinke, Andrea
O'Connell, Kevin F.
Zachariae, Wolfgang
Myers, Eugene
Hyman, Anthony A.
TI Limiting Amounts of Centrosome Material Set Centrosome Size in C.
elegans Embryos
SO CURRENT BIOLOGY
LA English
DT Article
ID BIOLOGICAL PATTERN FORMATION; POLO-LIKE KINASES; CAENORHABDITIS-ELEGANS;
MITOTIC SPINDLE; GAMMA-TUBULIN; CENTRIOLE DUPLICATION; PROTEIN SPD-2;
CELL-DIVISION; MATURATION; LENGTH
AB Background: The ways in which cells set the size of intracellular structures is an important but largely unsolved problem [1]. Early embryonic divisions pose special problems in this regard. Many checkpoints common in somatic cells are missing from these divisions, which are characterized by rapid reductions in cell size and short cell cycles [2]. Embryonic cells must therefore possess simple and robust mechanisms that allow the size of many of their intracellular structures to rapidly scale with cell size.
Results: Here, we study the mechanism by which one structure, the centrosome, scales in size during the early embryonic divisions of C. elegans. We show that centrosome size is directly related to cell size and is independent of lineage. Two findings suggest that the total amount of maternally supplied centrosome proteins could limit centrosome size. First, the combined volume of all centrosomes formed at any one time in the developing embryo is constant. Second, the total volume of centrosomes in any one cell is independent of centrosome number. By increasing the amount of centrosome proteins in the cell, we provide evidence that one component that limits centrosome size is the conserved pericentriolar material protein SPD-2 [3], which we show binds to and targets polo-like kinase 1 [3, 4] to centrosomes.
Conclusions: We propose a limiting component hypothesis, in which the volume of the cell sets centrosome size by limiting the total amount of centrosome components. This idea could be a general mechanism for setting the size of intracellular organelles during development.
C1 [Decker, Markus; Jaensch, Steffen; Pozniakovsky, Andrei; Zinke, Andrea; Zachariae, Wolfgang; Hyman, Anthony A.] Max Planck Inst Cell Biol & Genet, D-01307 Dresden, Germany.
[Jaensch, Steffen; Myers, Eugene] Howard Hughes Med Inst, Ashburn, VA 20147 USA.
[O'Connell, Kevin F.] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20894 USA.
RP Hyman, AA (reprint author), Max Planck Inst Cell Biol & Genet, D-01307 Dresden, Germany.
EM hyman@mpi-cbg.de
RI Hyman, Anthony/B-3917-2017
OI Hyman, Anthony/0000-0003-3664-154X
FU Max Planck Society; Alexander-von-Humbold Stiftung
FX We thank Cliff Brangwynne, David Zwicker, and Frank Julicher for
essential discussions on centrosome growth. We also wish to thank
Suzanne Eaton, Cliff Brangwyne, and Jordan Raft for critical reading of
the manuscript; Stephan Preibisch for collaborating on SPIM imaging; and
Jan Peychl and Britta Schroth-Diez for microscope support. We are also
grateful to Zoltan Maliga, Mike Boxem, and Stuart Milstein for support
with mapping protein-protein interactions; Horatiu Fantana for bead
injections; and the Max Planck Society and the Alexander-von-Humbold
Stiftung for funding.
NR 45
TC 72
Z9 74
U1 1
U2 10
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0960-9822
EI 1879-0445
J9 CURR BIOL
JI Curr. Biol.
PD AUG 9
PY 2011
VL 21
IS 15
BP 1259
EP 1267
DI 10.1016/j.cub.2011.06.002
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 806IP
UT WOS:000293801400017
PM 21802300
ER
PT J
AU Doeller, CF
Kaplan, R
AF Doeller, Christian F.
Kaplan, Raphael
TI Parahippocampal Cortex: Translating Vision into Space
SO CURRENT BIOLOGY
LA English
DT Editorial Material
ID REPRESENTATION; NAVIGATION; CONTEXT; NETWORK; MEMORY; SCENES; CELLS
C1 [Doeller, Christian F.] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Ctr Cognit Neuroimaging, NL-6525 ED Nijmegen, Netherlands.
[Kaplan, Raphael] UCL, NIMH UCL Joint Grad Partnership Program Neurosci, London, England.
[Kaplan, Raphael] UCL, UCL Inst Cognit Neurosci, London, England.
[Kaplan, Raphael] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
RP Doeller, CF (reprint author), Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Ctr Cognit Neuroimaging, NL-6525 ED Nijmegen, Netherlands.
EM christian.doeller@donders.ru.nl
RI Doeller, Christian/E-6376-2012;
OI Kaplan, Raphael/0000-0002-5023-1566
NR 20
TC 4
Z9 4
U1 4
U2 9
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0960-9822
J9 CURR BIOL
JI Curr. Biol.
PD AUG 9
PY 2011
VL 21
IS 15
BP R589
EP R591
DI 10.1016/j.cub.2011.06.023
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 806IP
UT WOS:000293801400011
PM 21820624
ER
PT J
AU Knowler, WC
AF Knowler, William C.
TI Prevention of Type 2 Diabetes How and in Whom?
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Editorial Material
ID IMPAIRED GLUCOSE-TOLERANCE; LIFE-STYLE; PROGRAM; METFORMIN
C1 NIDDK, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ 85014 USA.
RP Knowler, WC (reprint author), NIDDK, Diabet Epidemiol & Clin Res Sect, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA.
EM knowler@nih.gov
FU Intramural NIH HHS
NR 11
TC 2
Z9 2
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD AUG 8
PY 2011
VL 171
IS 15
BP 1361
EP 1362
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 804GR
UT WOS:000293642800010
PM 21824949
ER
PT J
AU Vilboux, T
Ciccone, C
Blancato, JK
Cox, GF
Deshpande, C
Introne, WJ
Gahl, WA
Smith, ACM
Huizing, M
AF Vilboux, Thierry
Ciccone, Carla
Blancato, Jan K.
Cox, Gerald F.
Deshpande, Charu
Introne, Wendy J.
Gahl, William A.
Smith, Ann C. M.
Huizing, Marjan
TI Molecular Analysis of the Retinoic Acid Induced 1 Gene (RAI1) in
Patients with Suspected Smith-Magenis Syndrome without the 17p11.2
Deletion
SO PLOS ONE
LA English
DT Article
ID HERMANSKY-PUDLAK-SYNDROME; SYNDROME DEL 17P11.2; REAL-TIME PCR;
INTERSTITIAL DELETION; ALAGILLE-SYNDROME; HUMAN JAGGED1; MUTATIONS;
EXPRESSION; PHENOTYPE; DISEASE
AB Smith-Magenis syndrome (SMS) is a complex neurobehavioral disorder characterized by multiple congenital anomalies. The syndrome is primarily ascribed to a similar to 3.7 Mb de novo deletion on chromosome 17p11.2. Haploinsufficiency of multiple genes likely underlies the complex clinical phenotype. RAI1 (Retinoic Acid Induced 1) is recognized as a major gene involved in the SMS phenotype. Extensive genetic and clinical analyses of 36 patients with SMS-like features, but without the 17p11.2 microdeletion, yielded 10 patients with RAI1 variants, including 4 with de novo deleterious mutations, and 6 with novel missense variants, 5 of which were familial. Haplotype analysis showed two major RAI1 haplotypes in our primarily Caucasian cohort; the novel RAI1 variants did not occur in a preferred haplotype. RNA analysis revealed that RAI1 mRNA expression was significantly decreased in cells of patients with the common 17p11.2 deletion, as well as in those with de novo RAI1 variants. Expression levels varied in patients with familial RAI1 variants and in non-17p11.2 deleted patients without identified RAI1 defects. No correlation between SNP haplotype and RAI1 expression was found. Two clinical features, ocular abnormalities and polyembolokoilomania (object insertion), were significantly correlated with decreased RAI1 expression. While not significantly correlated, the presence of hearing loss, seizures, hoarse voice, childhood onset of obesity and specific behavioral aspects and the absence of immunologic abnormalities and cardiovascular or renal structural anomalies, appeared to be specific for the de novo RAI1 subgroup. Recognition of the combination of these features will assist in referral for RAI1 analysis of patients with SMS-like features without detectable microdeletion of 17p11.2. Moreover, RAI1 expression emerged as a genetic target for development of therapeutic interventions for SMS.
C1 [Vilboux, Thierry; Ciccone, Carla; Gahl, William A.; Huizing, Marjan] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Blancato, Jan K.] Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA.
[Cox, Gerald F.] Harvard Univ, Sch Med, Dept Pediat, Div Genet,Childrens Hosp Boston, Boston, MA 02115 USA.
[Deshpande, Charu] Guys Hosp, Dept Genet, London SE1 9RT, England.
[Introne, Wendy J.; Gahl, William A.; Smith, Ann C. M.] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA.
[Cox, Gerald F.] Genzyme Corp, Cambridge, MA USA.
RP Vilboux, T (reprint author), NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
EM mhuizing@mail.nih.gov
FU National Human Genome Research Institute, National Institutes of Health,
Bethesda, Maryland, United States of America
FX This work was supported by the Intramural Research Program of the
National Human Genome Research Institute, National Institutes of Health,
Bethesda, Maryland, United States of America. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 59
TC 16
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U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 8
PY 2011
VL 6
IS 8
AR e22861
DI 10.1371/journal.pone.0022861
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 806AM
UT WOS:000293773300010
PM 21857958
ER
PT J
AU Engmann, C
Ditekemena, J
Jehan, I
Garces, A
Phiri, M
Thorsten, V
Mazariegos, M
Chomba, E
Pasha, O
Tshefu, A
McClure, EM
Wallace, D
Goldenberg, RL
Carlo, WA
Wright, LL
Bose, C
AF Engmann, Cyril
Ditekemena, John
Jehan, Imtiaz
Garces, Ana
Phiri, Mutinta
Thorsten, Vanessa
Mazariegos, Manolo
Chomba, Elwyn
Pasha, Omrana
Tshefu, Antoinette
McClure, Elizabeth M.
Wallace, Dennis
Goldenberg, Robert L.
Carlo, Waldemar A.
Wright, Linda L.
Bose, Carl
TI Classifying perinatal mortality using verbal autopsy: is there a role
for nonphysicians?
SO POPULATION HEALTH METRICS
LA English
DT Article
ID NEONATAL DEATHS; AFRICA; COMMUNITY; VALIDITY; MODEL; BIRTH; NEPAL
AB Background: Because of a physician shortage in many low-income countries, the use of nonphysicians to classify perinatal mortality (stillbirth and early neonatal death) using verbal autopsy could be useful.
Objective: To determine the extent to which underlying perinatal causes of deaths assigned by nonphysicians in Guatemala, Pakistan, Zambia, and the Democratic Republic of the Congo using a verbal autopsy method are concordant with underlying perinatal cause of death assigned by physician panels.
Methods: Using a train-the-trainer model, 13 physicians and 40 nonphysicians were trained to determine cause of death using a standardized verbal autopsy training program. Subsequently, panels of two physicians and individual nonphysicians from this trained cohort independently reviewed verbal autopsy data from a sample of 118 early neonatal deaths and 134 stillbirths. With the cause of death assigned by the physician panel as the reference standard, sensitivity, specificity, positive and negative predictive values, and cause-specific mortality fractions were calculated to assess nonphysicians' coding responses. Robustness criteria to assess how well nonphysicians performed were used.
Results: Causes of early neonatal death and stillbirth assigned by nonphysicians were concordant with physician-assigned causes 47% and 57% of the time, respectively. Tetanus filled robustness criteria for early neonatal death, and cord prolapse filled robustness criteria for stillbirth.
Conclusions: There are significant differences in underlying cause of death as determined by physicians and nonphysicians even when they receive similar training in cause of death determination. Currently, it does not appear that nonphysicians can be used reliably to assign underlying cause of perinatal death using verbal autopsy.
C1 [Engmann, Cyril; Bose, Carl] Univ N Carolina, Dept Pediat, Chapel Hill, NC 27515 USA.
[Engmann, Cyril; Bose, Carl] Univ N Carolina, Dept Maternal Child Hlth, Chapel Hill, NC USA.
[Ditekemena, John; Tshefu, Antoinette] Kinshasa Sch Publ Hlth, Kinshasa, Zaire.
[Jehan, Imtiaz; Pasha, Omrana] Aga Khan Univ, Dept Community Hlth Sci, Karachi, Pakistan.
[Garces, Ana] IMSALUD San Carlos Univ, Guatemala City, Guatemala.
[Phiri, Mutinta; Chomba, Elwyn] Univ Teaching Hosp, Dept Pediat & Child Hlth, Lusaka, Zambia.
[Thorsten, Vanessa; McClure, Elizabeth M.; Wallace, Dennis] Res Triangle Inst, Durham, NC USA.
[Mazariegos, Manolo] INCAP, Guatemala City, Guatemala.
[Goldenberg, Robert L.] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA.
[Carlo, Waldemar A.] Univ Alabama, Dept Pediat, Birmingham, AL USA.
[Wright, Linda L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Engmann, C (reprint author), Univ N Carolina, Dept Pediat, Chapel Hill, NC 27515 USA.
EM cengmann@med.unc.edu
FU NICHD NIH HHS [U01 HD040636]
NR 31
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Z9 2
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1478-7954
J9 POPUL HEALTH METR
JI Popul. Health Metr.
PD AUG 5
PY 2011
VL 9
AR 42
DI 10.1186/1478-7954-9-42
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 891LX
UT WOS:000300219600003
PM 21819582
ER
PT J
AU Snipes, SA
Sellers, SL
Tafawa, AO
Cooper, LA
Fields, JC
Bonham, VL
AF Snipes, Shedra Amy
Sellers, Sherrill L.
Tafawa, Adebola Odunlami
Cooper, Lisa A.
Fields, Julie C.
Bonham, Vence L.
TI Is race medically relevant? A qualitative study of physicians' attitudes
about the role of race in treatment decision-making
SO BMC HEALTH SERVICES RESEARCH
LA English
DT Article
ID RACIAL CATEGORIES; AFRICAN DESCENT; HEART-FAILURE; HEALTH-CARE;
ETHNICITY; MEDICINE; DISPARITIES; IMPLICIT; BIAS
AB Background: The role of patient race in medical decision-making is heavily debated. While some evidence suggests that patient race can be used by physicians to predict disease risk and determine drug therapy, other studies document bias and stereotyping by physicians based on patient race. It is critical, then, to explore physicians' attitudes regarding the medical relevance of patient race.
Methods: We conducted a qualitative study in the United States using ten focus groups of physicians stratified by self-identified race (black or white) and led by race-concordant moderators. Physicians were presented with a medical vignette about a patient (whose race was unknown) with Type 2 diabetes and untreated hypertension, who was also a current smoker. Participants were first asked to discuss what medical information they would need to treat the patient. Then physicians were asked to explicitly discuss the importance of race to the hypothetical patient's treatment. To identify common themes, codes, key words and physician demographics were compiled into a comprehensive table that allowed for examination of similarities and differences by physician race. Common themes were identified using the software package NVivo (QSR International, v7).
Results: Forty self-identified black and 50 self-identified white physicians participated in the study. All physicians regardless of their own race - believed that medical history, family history, and weight were important for making treatment decisions for the patient. However, black and white physicians reported differences in their views about the relevance of race. Several black physicians indicated that patient race is a central factor for choosing treatment options such as aggressive therapies, patient medication and understanding disease risk. Moreover, many black physicians considered patient race important to understand the patient's views, such as alternative medicine preferences and cultural beliefs about illness. However, few white physicians explicitly indicated that the patient's race was important over-and-above medical history. Instead, white physicians reported that the patient should be treated aggressively regardless of race.
Conclusions: This investigation adds to our understanding about how physicians in the United States consider race when treating patients, and sheds light on issues physicians face when deciding the importance of race in medical decision-making.
C1 [Snipes, Shedra Amy] Penn State Univ, University Pk, PA 16802 USA.
[Sellers, Sherrill L.] Miami Univ, Oxford, OH 45056 USA.
[Tafawa, Adebola Odunlami; Fields, Julie C.; Bonham, Vence L.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
[Tafawa, Adebola Odunlami] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Cooper, Lisa A.; Fields, Julie C.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21287 USA.
RP Snipes, SA (reprint author), Penn State Univ, 315 Hlth & Human Dev E, University Pk, PA 16802 USA.
EM sas84@psu.edu
RI Snipes, Shedra/L-2764-2015
OI Snipes, Shedra/0000-0001-8965-0429
FU Division of Intramural Research of the National Human Genome Research
Institute, National Institutes of Health; National Center on Minority
Health and Health Disparities, National Institutes of Health
[5-P60-MD000503]; W.K Kellogg Foundation [P0117943]; University of Texas
School of Public Health - National Cancer Institute/NIH [R25-CA-57712]
FX This research was supported in part by the Division of Intramural
Research of the National Human Genome Research Institute, National
Institutes of Health. Writing support was granted in part by an EXPORT
Center of Excellence grant provided by the National Center on Minority
Health and Health Disparities, National Institutes of Health
(5-P60-MD000503), and the W.K Kellogg Foundation (Grant #: P0117943).
Revisions of the manuscript, edits and preparation for submission were
funded by the Post-doctoral Fellowship, University of Texas School of
Public Health Cancer Education and Career Development Program - National
Cancer Institute/NIH Grant R25-CA-57712. The content is solely the
responsibility of the authors and does not represent the official views
of the National Human Genome Research Institute, National Cancer
Institute, National Institutes of Health, or Department of Health and
Human Services.
NR 27
TC 13
Z9 13
U1 0
U2 13
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1472-6963
J9 BMC HEALTH SERV RES
JI BMC Health Serv. Res.
PD AUG 5
PY 2011
VL 11
AR 183
DI 10.1186/1472-6963-11-183
PG 10
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 815XR
UT WOS:000294563800001
PM 21819597
ER
PT J
AU Lakhashe, SK
Velu, V
Sciaranghella, G
Siddappa, NB
DiPasquale, JM
Hemashettar, G
Yoon, JK
Rasmussen, RA
Yang, F
Lee, SJ
Montefiori, DC
Novembre, FJ
Villinger, F
Amara, RR
Kahn, M
Hu, SL
Li, SF
Li, ZX
Frankel, FR
Robert-Guroff, M
Johnson, WE
Lieberman, J
Ruprecht, RM
AF Lakhashe, Samir K.
Velu, Vijayakumar
Sciaranghella, Gaia
Siddappa, Nagadenahalli B.
DiPasquale, Janet M.
Hemashettar, Girish
Yoon, John K.
Rasmussen, Robert A.
Yang, Feng
Lee, Sandra J.
Montefiori, David C.
Novembre, Francis J.
Villinger, Francois
Amara, Rama Rao
Kahn, Maria
Hu, Shiu-Lok
Li, Sufen
Li, Zhongxia
Frankel, Fred R.
Robert-Guroff, Marjorie
Johnson, Welkin E.
Lieberman, Judy
Ruprecht, Ruth M.
TI Prime-boost vaccination with heterologous live vectors encoding SIV gag
and multimeric HIV-1 gp160 protein: Efficacy against repeated mucosal R5
clade C SHIV challenges
SO VACCINE
LA English
DT Article
DE Live attenuated Listeria monocytogenes; Replication-competent
adenovirus; Live oral vaccine; HIV/AIDS vaccine; Multimeric HIV clade C
gp160; Prime-boost vaccination; alpha 4 beta 7 integrin
ID IMMUNODEFICIENCY-VIRUS TYPE-1; CELL-MEDIATED-IMMUNITY;
LISTERIA-MONOCYTOGENES; RHESUS MACAQUES; PROTECTIVE EFFICACY; INTEGRIN
ALPHA(4)BETA(7); REPLICATION-COMPETENT; CANCER-IMMUNOTHERAPY; SHIV89.6P
CHALLENGE; ADENOVIRUS VACCINES
AB We sought to induce primate immunodeficiency virus-specific cellular and neutralizing antibody (nAb) responses in rhesus macaques (RM) through a bimodal vaccine approach. RM were immunized intragastrically (i.g.) with the live-attenuated Listeria monocytogenes (Lm) vector Lmdd-BdopSIVgag encoding SIVmac239gag. SIV Gag-specific cellular responses were boosted by intranasal and intratracheal administration of replication-competent adenovirus (Ad5hr-SIVgag) encoding the same gag. To broaden antiviral immunity, the RM were immunized with multimeric HIV clade C (HIV-C) gp160 and HIV Tat. SIV Gag-specific cellular immune responses and HIV-1 nAb developed in some RM. The animals were challenged intrarectally with five low doses of R5 SHIV-1157ipEL-p, encoding a heterologous HIV-C Env (22.1% divergent to the Env immunogen). All five controls became viremic. One out of ten vaccinees was completely protected and another had low peak viremia. Sera from the completely and partially protected RM neutralized the challenge virus >90%; these RM also had strong SIV Gag-specific proliferation of CD8(+) T cells. Peak and area under the curve of plasma viremia (during acute phase) among vaccinees was lower than for controls, but did not attain significance. The completely protected RM showed persistently low numbers of the alpha 4 beta 7-expressing CD4(+) T cells; the latter have been implicated as preferential virus targets in vivo. Thus, vaccine-induced immune responses and relatively lower numbers of potential target cells were associated with protection. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Lakhashe, Samir K.; Sciaranghella, Gaia; Siddappa, Nagadenahalli B.; Hemashettar, Girish; Yoon, John K.; Rasmussen, Robert A.; Yang, Feng; Lee, Sandra J.; Ruprecht, Ruth M.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA.
[Lakhashe, Samir K.; Sciaranghella, Gaia; Siddappa, Nagadenahalli B.; Rasmussen, Robert A.; Yang, Feng; Lee, Sandra J.; Ruprecht, Ruth M.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA.
[Velu, Vijayakumar; Novembre, Francis J.; Villinger, Francois; Amara, Rama Rao] Emory Univ, Yerkes Natl Primate Res Ctr, Div Microbiol & Immunol, Atlanta, GA 30329 USA.
[Velu, Vijayakumar; Novembre, Francis J.; Amara, Rama Rao] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30329 USA.
[DiPasquale, Janet M.; Robert-Guroff, Marjorie] NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA.
[Montefiori, David C.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA.
[Villinger, Francois] Emory Univ, Yerkes Natl Primate Res Ctr, Dept Pathol, Atlanta, GA 30329 USA.
[Kahn, Maria; Hu, Shiu-Lok] Univ Washington, Seattle, WA 98195 USA.
[Li, Sufen; Li, Zhongxia; Frankel, Fred R.] Univ Penn, Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA.
[Johnson, Welkin E.] New England Primate Res Ctr, Southborough, MA 01772 USA.
[Lieberman, Judy] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
[Lieberman, Judy] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 450 Brookline Ave, Boston, MA 02215 USA.
EM ruth_ruprecht@dfci.harvard.edu
RI Lakhashe, Samir/F-1150-2014; Lieberman, Judy/A-2717-2015; Hu,
Shiu-Lok/A-3196-2008;
OI Hu, Shiu-Lok/0000-0003-4336-7964; Byrareddy, Siddappa
/0000-0002-7423-1763; Velu, Vijayakumar/0000-0003-4238-1924
FU NIH [P01 AI054558, P01 AI048240, RR-00165, RR00168]; Center for AIDS
Research Immunology [P30 AI060354, P30 AI 050409]; NIH, National Cancer
Institute
FX We thank Julie Johnson-McGrath for assistance with the preparation of
this manuscript, Stephanie Ehnert for the coordination of the primate
studies, and Dr. Richard Raybourne (formerly of the Food and Drug
Administration) for assistance and protocols to assess anti-Lm immune
responses. We thank Stefan Kostense, Crucell Holland B.V., for providing
the Ad5-luciferase construct. We thank the NIH AIDS Research and
Reference Reagent Program for reagents. This study was supported by NIH
grants P01 AI054558 to FF, FJN, RMR and JL and P01 AI048240 to RMR,
RR-00165 to the YNPRC, RR00168 to the NEPRC, and by Center for AIDS
Research Immunology Core grants, P30 AI060354 and P30 AI 050409, and in
part by the Intramural Research Program of the NIH, National Cancer
Institute.
NR 71
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U1 1
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD AUG 5
PY 2011
VL 29
IS 34
BP 5611
EP 5622
DI 10.1016/j.vaccine.2011.06.017
PG 12
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 810RW
UT WOS:000294145800006
PM 21693155
ER
PT J
AU Khurana, S
Larkin, C
Verma, S
Joshi, MB
Fontana, J
Steven, AC
King, LR
Manischewitz, J
McCormick, W
Gupta, RK
Golding, H
AF Khurana, Surender
Larkin, Christopher
Verma, Swati
Joshi, Manju B.
Fontana, Juan
Steven, Alasdair C.
King, Lisa R.
Manischewitz, Jody
McCormick, William
Gupta, Rajesh K.
Golding, Hana
TI Recombinant HA1 produced in E. coli forms functional oligomers and
generates strain-specific SRID potency antibodies for pandemic influenza
vaccines
SO VACCINE
LA English
DT Article
DE Pandemic influenza; Vaccine potency; Single-radial immunodiffusion
assay; H5N1; H1N1; Vaccine
ID SINGLE-RADIAL-IMMUNODIFFUSION; UNIVERSAL ANTIBODIES;
ELECTRON-MICROSCOPY; VIRUS PROTEINS; UNITED-STATES; A VIRUS;
HEMAGGLUTININ; HUMANS; QUANTIFICATION; RESOLUTION
AB Vaccine production and initiation of mass vaccination is a key factor in rapid response to new influenza pandemic. During the 2009-2010 H1N1 pandemic, several bottlenecks were identified, including the delayed availability of vaccine potency reagents. Currently, antisera for the single-radial immunodiffusion (SRID) potency assay are generated in sheep immunized repeatedly with HA released and purified after bromelain-treatment of influenza virus grown in eggs. This approach was a major bottleneck for pandemic H1N1 (H1N1pdm09) potency reagent development in 2009. Alternative approaches are needed to make HA immunogens for generation of SRID reagents in the shortest possible time. In this study, we found that properly folded recombinant HA1 globular domain (rHA1) from several type A viruses including H1N1pdm09 and two H5N1 viruses could be produced efficiently using a bacterial expression system and subsequent purification. The rHA1 proteins were shown to form functional oligomers of trimers, similar to virus derived HA, and elicited high titer of neutralizing antibodies in rabbits and sheep. Importantly, the immune sera formed precipitation rings with reference antigens in the SRID assay in a dose-dependent manner. The HA contents in multiple H1N1 vaccine products from different manufacturers (and in several lots) as determined with the rHA1-generated sheep sera were similar to the values obtained with a traditionally generated sheep serum from NIBSC. We conclude that bacterially expressed recombinant HA1 proteins can be produced rapidly and used to generate SRID potency reagents shortly after new influenza strains with pandemic potential are identified. Published by Elsevier Ltd.
C1 [Khurana, Surender; Verma, Swati; King, Lisa R.; Manischewitz, Jody; Golding, Hana] US FDA, Div Viral Prod, CBER, Bethesda, MD 20892 USA.
[Larkin, Christopher; Joshi, Manju B.; McCormick, William; Gupta, Rajesh K.] US FDA, Div Prod Qual, CBER, Bethesda, MD 20892 USA.
[Fontana, Juan; Steven, Alasdair C.] NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA.
RP Golding, H (reprint author), US FDA, Div Viral Prod, CBER, Bethesda, MD 20892 USA.
EM hana.golding@fda.hhs.gov
RI Fontana, Juan/A-9138-2009
OI Fontana, Juan/0000-0002-9084-2927
FU BARDA/HHS; DMID IAA [224-10-1006]; National Institute of Arthritis and
Musculoskeletal and Skin Diseases of the National Institutes of Health
FX We thank Vladimir Lugovtsev, and Falko Schmeisser for a thorough review
of the manuscript. This work was partly supported funds from BARDA/HHS,
by DMID IAA 224-10-1006, and by the Intramural Research Program of the
National Institute of Arthritis and Musculoskeletal and Skin Diseases of
the National Institutes of Health. The funders had no role in study
design, data collection and analysis, or preparation of the manuscript.
NR 30
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U2 5
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD AUG 5
PY 2011
VL 29
IS 34
BP 5657
EP 5665
DI 10.1016/j.vaccine.2011.06.014
PG 9
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 810RW
UT WOS:000294145800012
PM 21704111
ER
PT J
AU Gil, C
Climent, N
Garcia, F
Hurtado, C
Nieto-Marquez, S
Leon, A
Garcia, MT
Rovira, C
Miralles, L
Dalmau, J
Pumarola, T
Almela, M
Martinez-Picado, J
Lifson, JD
Zamora, L
Miro, JM
Brander, C
Clotet, B
Gallart, T
Gatell, JM
AF Gil, Cristina
Climent, Noria
Garcia, Felipe
Hurtado, Carmen
Nieto-Marquez, Sara
Leon, Agathe
Teresa Garcia, M.
Rovira, Cristina
Miralles, Laia
Dalmau, Judith
Pumarola, Tomas
Almela, Manel
Martinez-Picado, Javier
Lifson, Jeffrey D.
Zamora, Laura
Miro, Jose M.
Brander, Christian
Clotet, Bonaventura
Gallart, Teresa
Gatell, Jose M.
TI Ex vivo production of autologous whole inactivated HIV-1 for clinical
use in therapeutic vaccines
SO VACCINE
LA English
DT Article
DE Autologous HIV-1 immunogen; Heat inactivated HIV-1; Therapeutic vaccine
ID HUMAN-IMMUNODEFICIENCY-VIRUS; DENDRITIC-CELL VACCINE; B METHYL-ESTER;
ANTIRETROVIRAL TREATMENT; ENVELOPE GLYCOPROTEINS; CHEMICAL INACTIVATION;
INFECTED PATIENTS; TYPE-1; RESPONSES; IMMUNIZATION
AB This study provides a detailed description and characterization of the preparation of individualized lots of autologous heat inactivated HIV-1 virions used as immunogen in a clinical trial designed to test an autologous dendritic-cell-based therapeutic HIV-1 vaccine (Clinical Trial DCV-2, NCT00402142). For each participant, ex vivo isolation and expansion of primary virus were performed by co-culturing CD4-enriched PBMCs from the HIV-1-infected patient with PBMC from HIV-seronegative unrelated healthy volunteer donors. The viral supernatants were heat-inactivated and concentrated to obtain 1 mL of autologous immunogen, which was used to load autologous dendritic cells of each patient. High sequence homology was found between the inactivated virus immunogen and the HIV-1 circulating in plasma at the time of HIV-1 isolation. Immunogens contained up to 10(9) HIV-1 RNA copies/mL showed considerably reduced infectivity after heat inactivation (median of 5.6 log(10)), and were free of specified adventitious agents. The production of individualized lots of immunogen based on autologous inactivated HIV-1 virus fulfilling clinical-grade good manufacturing practice proved to be feasible, consistent with predetermined specifications, and safe for use in a clinical trial designed to test autologous dendritic cell-based therapeutic HIV-1 vaccine. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Gil, Cristina; Garcia, Felipe; Miro, Jose M.; Gatell, Jose M.] Hosp Clin Barcelona, Infect Dis Serv, E-08036 Barcelona, Spain.
[Gil, Cristina; Garcia, Felipe; Miro, Jose M.; Gatell, Jose M.] Hosp Clin Barcelona, AIDS Unit, E-08036 Barcelona, Spain.
[Pumarola, Tomas; Almela, Manel; Gallart, Teresa] Univ Barcelona, Hosp Clin Barcelona, E-08007 Barcelona, Spain.
[Dalmau, Judith; Martinez-Picado, Javier; Brander, Christian; Clotet, Bonaventura] Hosp Badalona Germans Trias & Pujol, Inst Recerca SIDA IrsiCaixa HIVACAT, Barcelona, Spain.
[Martinez-Picado, Javier; Brander, Christian] ICREA, Barcelona, Spain.
[Lifson, Jeffrey D.] NCI Frederick, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Gil, C (reprint author), Hosp Clin Barcelona, Infect Dis Serv, Villarroel 170, E-08036 Barcelona, Spain.
EM cgil@clinic.ub.es
RI Martinez-Picado, Javier/G-5507-2012; Leon, Agathe/K-9851-2015; Garcia,
Felipe/F-4242-2014;
OI Martinez-Picado, Javier/0000-0002-4916-2129; Leon,
Agathe/0000-0002-1198-5090; Garcia, Felipe/0000-0001-7658-5832; Brander,
Christian/0000-0002-0548-5778
FU FIPSE [2005-VA36536]; Fondo de Investigaciones Sanitarias [PI061259];
ORVACS [Manon07]; Institut de Salud Carlos III- Red de Investigacion en
sida [RD06/0006]; HIVACAT (Projecte de recerca de la vacuna de la SIDA);
National Cancer Institute, National Institutes of Health (USA)
[HHSN261200800001E]; Institut d'Investigacions Biomediques August Pi i
Sunyer (IDIBAPS); Instituto de Salud Carlos III, Madrid (Spain)
[INT10/219]; Departament de Salut de la Generalitat de Catalunya,
Barcelona (Spain)
FX This study was supported in part by FIPSE (2005-VA36536), Fondo de
Investigaciones Sanitarias (PI061259), ORVACS (Manon07), Institut de
Salud Carlos III- Red de Investigacion en sida (RD06/0006) and HIVACAT
(Projecte de recerca de la vacuna de la SIDA) and in part with federal
funds from the National Cancer Institute, National Institutes of Health
(USA) under contract HHSN261200800001E. Dr Felipe Garcia received a
Research Grant from the "Institut d'Investigacions Biomediques August Pi
i Sunyer (IDIBAPS)". Dr. Jose M. Miro holds an INT10/219 Intensification
Research Grant (13SNS & PRICS programs) from the "Instituto de Salud
Carlos III, Madrid (Spain)" and the "Departament de Salut de la
Generalitat de Catalunya, Barcelona (Spain)".
NR 60
TC 5
Z9 5
U1 0
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD AUG 5
PY 2011
VL 29
IS 34
BP 5711
EP 5724
DI 10.1016/j.vaccine.2011.05.096
PG 14
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 810RW
UT WOS:000294145800020
PM 21679735
ER
PT J
AU Wan, WZ
Lim, JK
Lionakis, MS
Rivollier, A
McDermott, DH
Kelsall, BL
Farber, JM
Murphy, PM
AF Wan, Wuzhou
Lim, Jean K.
Lionakis, Michail S.
Rivollier, Aymeric
McDermott, David H.
Kelsall, Brian L.
Farber, Joshua M.
Murphy, Philip M.
TI Genetic Deletion of Chemokine Receptor Ccr6 Decreases Atherogenesis in
ApoE-Deficient Mice
SO CIRCULATION RESEARCH
LA English
DT Article
DE atherosclerosis; inflammation; monocytes; aorta
ID RHEUMATOID-ARTHRITIS; MACROPHAGE ACCUMULATION; BACTERIAL-INFECTION;
INFLAMMATORY SITES; BONE-MARROW; T-CELLS; ATHEROSCLEROSIS; RECRUITMENT;
MECHANISMS; MONOCYTES
AB Rationale: The chemokine receptor Ccr6 is a G-protein-coupled receptor expressed on various types of leukocytes identified in mouse atherosclerotic lesions. Recent evidence suggests that both CCR6 and its ligand CCL20 are also present in human atheroma; however, their functional roles in atherogenesis remain undefined.
Objective: Our objective was to delineate the role of Ccr6 in atherogenesis in the apolipoprotein E-deficient (ApoE(-/-)) mouse model of atherosclerosis.
Methods and Results: Both Ccr6 and Ccl20 are expressed in atherosclerotic aorta from ApoE(-/-) mice. Aortic lesion area in Ccr6(-/-) ApoE(-/-) mice was similar to 40% and similar to 30% smaller than in Ccr6(+/+) ApoE(-/-) mice at 16 and 24 weeks of age, respectively. Transplantation of bone marrow from Ccr6(-/-) mice into ApoE(-/-) mice resulted in similar to 40% less atherosclerotic lesion area than for bone marrow from Ccr6(-/-) mice; lesions in Ccr6(-/-) ApoE(-/-) mice had 44% less macrophage content than lesions in Ccr6(+/+) ApoE(-/-) mice. Ccr6 was expressed on a subset of primary mouse monocytes. Accordingly, Ccl20 induced chemotaxis of primary monocytes from wild-type but not Ccr6(-/-) mice; moreover, Ccl20 induced monocytosis in ApoE(-/-) mice in vivo. Consistent with this, we observed 30% fewer monocytes in circulating blood of Ccr6(-/-) ApoE(-/-) mice, mainly because of fewer CD11b(+)Ly6C(high) inflammatory monocytes.
Conclusions: Ccr6 promotes atherosclerosis in ApoE-deficient mice, which may be due in part to Ccr6 support of normal monocyte levels in blood, as well as direct Ccr6-dependent monocyte migration. (Circ Res. 2011;109:374-381.)
C1 [Wan, Wuzhou; Lim, Jean K.; Lionakis, Michail S.; Rivollier, Aymeric; McDermott, David H.; Kelsall, Brian L.; Farber, Joshua M.; Murphy, Philip M.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
RP Murphy, PM (reprint author), NIAID, Lab Mol Immunol, NIH, 9000 Rockville Pike,Bldg 10,Room 11N113, Bethesda, MD 20892 USA.
EM pmm@nih.gov
RI Wan, Wuhzou/H-8556-2013;
OI McDermott, David/0000-0001-6978-0867
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health.
NR 39
TC 29
Z9 30
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7330
EI 1524-4571
J9 CIRC RES
JI Circ.Res.
PD AUG 5
PY 2011
VL 109
IS 4
BP 374
EP 381
DI 10.1161/CIRCRESAHA.111.242578
PG 8
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 802IV
UT WOS:000293504100006
PM 21680896
ER
PT J
AU Srikantan, S
Gorospe, M
AF Srikantan, Subramanya
Gorospe, Myriam
TI UneCLIPsing HuR Nuclear Function
SO MOLECULAR CELL
LA English
DT Editorial Material
C1 [Srikantan, Subramanya; Gorospe, Myriam] NIA, Lab Mol Biol & Immunol, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Gorospe, M (reprint author), NIA, Lab Mol Biol & Immunol, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM myriam-gorospe@nih.gov
OI srikantan, subramanya/0000-0003-1810-6519
FU Intramural NIH HHS [ZIA AG000511-13]
NR 10
TC 9
Z9 9
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD AUG 5
PY 2011
VL 43
IS 3
BP 319
EP 321
DI 10.1016/j.molce1.2011.07.016
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 804VA
UT WOS:000293680900001
PM 21816340
ER
PT J
AU Xiao, H
Mizuguchi, G
Wisniewski, J
Huang, YZ
Wei, DB
Wu, C
AF Xiao, Hua
Mizuguchi, Gaku
Wisniewski, Jan
Huang, Yingzi
Wei, Debbie
Wu, Carl
TI Nonhistone Scm3 Binds to AT-Rich DNA to Organize Atypical Centromeric
Nucleosome of Budding Yeast
SO MOLECULAR CELL
LA English
DT Article
ID HISTONE FOLD DOMAIN; CENP-A; SACCHAROMYCES-CEREVISIAE; CHROMATIN; HJURP;
CORE; DEPOSITION; SEQUENCE; IDENTITY; CSE4
AB The molecular architecture of centromere-specific nucleosomes containing histone variant CenH3 is controversial. We have biochemically reconstituted two distinct populations of nucleosomes containing Saccharomyces cerevisiae CenH3 (Cse4). Reconstitution of octameric nucleosomes containing histones Cse4/H4/H2A/H2B is robust on noncentromere DNA, but inefficient on AT-rich centromere DNA. However, nonhistone Scm3, which is required for Cse4 deposition in vivo, facilitates in vitro reconstitution of Cse4/H4/Scm3 complexes on AT-rich centromere sequences. Scm3 has a nonspecific DNA binding domain that shows preference for AT-rich DNA and a histone chaperone domain that promotes specific loading of Cse4/H4. In live cells, Scm3-GFP is enriched at centromeres in all cell cycle phases. Chromatin immunoprecipitation confirms that Scm3 occupies centromere DNA throughout the cell cycle, even when Cse4 and H4 are temporarily dislodged in S phase. These findings suggest a model in which centromere-bound Scm3 aids recruitment of Cse4/H4 to assemble and maintain an H2A/H2B-deficient centromeric nucleosome.
C1 [Xiao, Hua; Mizuguchi, Gaku; Wisniewski, Jan; Huang, Yingzi; Wei, Debbie; Wu, Carl] NCI, Biochem & Mol Biol Lab, Bethesda, MD 20892 USA.
RP Wu, C (reprint author), NCI, Biochem & Mol Biol Lab, 37 Convent Dr,Bldg 37,Room 6068, Bethesda, MD 20892 USA.
EM carlwu@mail.nih.gov
FU National Cancer Institute
FX We thank Ed Luk for performing FAGS analysis; members of our laboratory
for helpful suggestions; and Mitch Smith, David Clark, Michael Lichten,
Victor Zhurkin, Kerry Bloom, and the reviewers for helpful comments on
the manuscript. We are grateful for the gift of 601 nucleosome
positioning sequences from Jon Widom. This manuscript is dedicated to
his memory. The work was supported by the intramural research program of
the National Cancer Institute.
NR 58
TC 40
Z9 40
U1 0
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD AUG 5
PY 2011
VL 43
IS 3
BP 369
EP 380
DI 10.1016/j.molce1.2011.07.009
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 804VA
UT WOS:000293680900007
PM 21816344
ER
PT J
AU Yuan, J
Cheng, KCC
Johnson, RL
Huang, RL
Pattaradilokrat, S
Liu, AN
Guha, R
Fidock, DA
Inglese, J
Wellems, TE
Austin, CP
Su, XZ
AF Yuan, Jing
Cheng, Ken Chih-Chien
Johnson, Ronald L.
Huang, Ruili
Pattaradilokrat, Sittiporn
Liu, Anna
Guha, Rajarshi
Fidock, David A.
Inglese, James
Wellems, Thomas E.
Austin, Christopher P.
Su, Xin-zhuan
TI Chemical Genomic Profiling for Antimalarial Therapies, Response
Signatures, and Molecular Targets
SO SCIENCE
LA English
DT Article
ID PLASMODIUM-FALCIPARUM MALARIA; IN-VITRO ACTIVITY; DRUG-RESISTANCE;
CHLOROQUINE RESISTANCE; DIGESTIVE VACUOLE; ARTEMISININ; GENE;
SUSCEPTIBILITY; AMODIAQUINE; DIVERSITY
AB Malaria remains a devastating disease largely because of widespread drug resistance. New drugs and a better understanding of the mechanisms of drug action and resistance are essential for fulfilling the promise of eradicating malaria. Using high-throughput chemical screening and genome-wide association analysis, we identified 32 highly active compounds and genetic loci associated with differential chemical phenotypes (DCPs), defined as greater than or equal to fivefold differences in half-maximum inhibitor concentration (IC50) between parasite lines. Chromosomal loci associated with 49 DCPs were confirmed by linkage analysis and tests of genetically modified parasites, including three genes that were linked to 96% of the DCPs. Drugs whose responses mapped to wild-type or mutant pfcrt alleles were tested in combination in vitro and in vivo, which yielded promising new leads for antimalarial treatments.
C1 [Cheng, Ken Chih-Chien; Johnson, Ronald L.; Huang, Ruili; Guha, Rajarshi; Inglese, James; Austin, Christopher P.] NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD 20895 USA.
[Yuan, Jing; Pattaradilokrat, Sittiporn; Liu, Anna; Wellems, Thomas E.; Su, Xin-zhuan] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
[Fidock, David A.] Columbia Univ, Med Ctr, Dept Microbiol & Immunol, New York, NY 10032 USA.
[Fidock, David A.] Columbia Univ, Med Ctr, Dept Med, New York, NY 10032 USA.
RP Austin, CP (reprint author), NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD 20895 USA.
EM austinc@mail.nih.gov; xsu@niaid.nih.gov
OI Fidock, David/0000-0001-6753-8938; Su, Xinzhuan/0000-0003-3246-3248
FU Division of Intramural Research at the National Institute of Allergy and
Infectious Diseases (NIAID); National Human Genome Research Institute;
NIH; Burroughs Wellcome Fund [R01 AI50234]
FX This work was supported by the Intramural Research Program of the
Division of Intramural Research at the National Institute of Allergy and
Infectious Diseases (NIAID), the National Human Genome Research
Institute, and the Director's Challenge Award Program, all at NIH.
Funding for the studies from D.A.F. was provided by R01 AI50234 and the
Burroughs Wellcome Fund.
NR 39
TC 81
Z9 81
U1 3
U2 31
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD AUG 5
PY 2011
VL 333
IS 6043
BP 724
EP 729
DI 10.1126/science.1205216
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 802LH
UT WOS:000293512100034
PM 21817045
ER
PT J
AU Gong, R
Wang, YP
Feng, Y
Zhao, Q
Dimitrov, DS
AF Gong, Rui
Wang, Yanping
Feng, Yang
Zhao, Qi
Dimitrov, Dimiter S.
TI Shortened Engineered Human Antibody CH2 Domains INCREASED STABILITY AND
BINDING TO THE HUMAN NEONATAL Fc RECEPTOR
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID IMMUNOGLOBULIN-G; PROTEINS; REGION; SCAFFOLDS; LYSOZYME; AFFINITY
AB The immunoglobulin (Ig) constant CH2 domain is critical for antibody effector functions. Isolated CH2 domains are promising scaffolds for construction of libraries containing diverse binders that could also confer some effector functions. We have shown previously that an isolated human CH2 domain is relatively unstable to thermally induced unfolding, but its stability can be improved by engineering an additional disulfide bond (Gong, R., Vu, B. K., Feng, Y., Prieto, D. A., Dyba, M. A., Walsh, J. D., Prabakaran, P., Veenstra, T. D., Tarasov, S. G., Ishima, R., and Dimitrov, D. S. (2009) J. Biol. Chem. 284, 14203-14210). We have hypothesized that the stability of this engineered antibody domain could be further increased by removing unstructured residues. To test our hypothesis, we removed the seven N-terminal residues that are in a random coil as suggested by our analysis of the isolated CH2 crystal structure and NMR data. The resulting shortened engineered CH2 (m01s) was highly soluble, monomeric, and remarkably stable, with a melting temperature (T(m)) of 82.6 degrees C, which is about 10 and 30 degrees C higher than those of the original stabilized CH2 (m01) and CH2, respectively. m01s and m01 were more resistant to protease digestion than CH2. A newly identified anti-CH2 antibody that recognizes a conformational epitope bound to m01s significantly better (> 10-fold higher affinity) than to CH2 and slightly better than to m01. m01s bound to a recombinant soluble human neonatal Fc receptor at pH 6.0 more strongly than CH2. These data suggest that shortening the m01 N terminus significantly increases stability without disrupting its conformation and that our approach for increasing stability and decreasing size by removing unstructured regions may also apply to other proteins.
C1 [Gong, Rui; Wang, Yanping; Feng, Yang; Zhao, Qi; Dimitrov, Dimiter S.] NCI, Prot Interact Grp, CCRNP, CCR,NIH, Frederick, MD 21702 USA.
[Wang, Yanping] NCI, SAIC Frederick Inc, NIH, Frederick, MD 21702 USA.
RP Dimitrov, DS (reprint author), NCI, Prot Interact Grp, CCRNP, CCR,NIH, Bldg 469,Rm 150B, Frederick, MD 21702 USA.
EM dimiter.dimitrov@nih.gov
FU National Institutes of Health; National Institutes of Health NIAID;
National Institutes of Health NCI Center for Cancer Research; National
Institutes of Health NCI [N01-CO-12400]
FX This work was supported by the National Institutes of Health Intramural
AIDS Targeted Antiviral Program (IATAP), the National Institutes of
Health NIAID Intramural Biodefense Program, and the National Institutes
of Health NCI Center for Cancer Research Intramural Research Program.
This work was supported, in whole or in part, by federal funds from
National Institutes of Health NCI Contract N01-CO-12400.
NR 20
TC 28
Z9 29
U1 1
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 5
PY 2011
VL 286
IS 31
BP 27288
EP 27293
DI 10.1074/jbc.M111.254219
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 799EZ
UT WOS:000293268700024
PM 21669873
ER
PT J
AU Kosaka-Suzuki, N
Suzuki, T
Pugacheva, EM
Vostrov, AA
Morse, HC
Loukinov, D
Lobanenkov, V
AF Kosaka-Suzuki, Natsuki
Suzuki, Teruhiko
Pugacheva, Elena M.
Vostrov, Alexander A.
Morse, Herbert C., III
Loukinov, Dmitri
Lobanenkov, Victor
TI Transcription Factor BORIS (Brother of the Regulator of Imprinted Sites)
Directly Induces Expression of a Cancer-Testis Antigen, TSP50, through
Regulated Binding of BORIS to the Promoter
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID C-MYC GENE; CTCF-BINDING; EPIGENETIC REGULATION; ENHANCER-BLOCKING;
CONTROL REGION; BREAST-CANCER; LUNG-CANCER; PROTEIN; CHROMATIN;
INSULATOR
AB Cancer-testis antigens (CTAs) are normally expressed in testis but are aberrantly expressed in a variety of cancers with varying frequency. More than 100 proteins have been identified as CTA including testes-specific protease 50 (TSP50) and the testis-specific paralogue of CCCTC-binding factor, BORIS (brother of the regulator of imprinted sites). Because many CTAs are considered as excellent targets for tumor immunotherapy, understanding the regulatory mechanisms governing their expression is important. In this study we demonstrate that BORIS is directly responsible for the transcriptional activation of TSP50. We found two BORIS binding sites in the TSP50 promoter that are highly conserved between mouse and human. Mutations of the binding sites resulted in loss of BORIS binding and the ability of BORIS to activate the promoter. However, although expression of BORIS was essential, it was not sufficient for high expression of TSP50 in cancer cells. Further studies showed that binding of BORIS to the target sites was methylation-independent but was diminished by nucleosomal occupancy consistent with the findings that high expression of TSP50 was associated with increased DNase I sensitivity and high BORIS occupancy of the promoter. These findings indicate that BORIS-induced expression of TSP50 is governed by accessibility and binding of BORIS to the promoter. To our knowledge this is the first report of regulated expression of one CTA by another to be validated in a physiological context.
C1 [Lobanenkov, Victor] NIAID, Mol Pathol Sect, Immunopathol Lab, NIH, Rockville, MD 20852 USA.
RP Lobanenkov, V (reprint author), NIAID, Mol Pathol Sect, Immunopathol Lab, NIH, Twinbrook 1,Rm 1417,MSC-8152,5640 Fishers Lane, Rockville, MD 20852 USA.
EM vlobanenkov@niaid.nih.gov
OI Lobanenkov, Victor/0000-0001-6665-3635; Morse,
Herbert/0000-0002-9331-3705
FU National Institutes of Health of the NIAID; Japan Society for the
Promotion of Science Research at the National Institutes of Health
FX This work was supported, in whole or in part, by the National Institutes
of Health Intramural Research Program of the NIAID. This work was also
supported by the Japan Society for the Promotion of Science Research
Fellowship for Japanese Biomedical and Behavioral Researchers at the
National Institutes of Health (to T. S.).
NR 50
TC 15
Z9 18
U1 0
U2 8
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 5
PY 2011
VL 286
IS 31
BP 27378
EP 27388
DI 10.1074/jbc.M111.243576
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 799EZ
UT WOS:000293268700033
PM 21659515
ER
PT J
AU Lu, CY
Tilan, JU
Everhart, L
Czarnecka, M
Soldin, SJ
Mendu, DR
Jeha, D
Hanafy, J
Lee, CK
Sun, JF
Izycka-Swieszewska, E
Toretsky, JA
Kitlinska, J
AF Lu, Congyi
Tilan, Jason U.
Everhart, Lindsay
Czarnecka, Magdalena
Soldin, Steven J.
Mendu, Damodara R.
Jeha, Dima
Hanafy, Jailan
Lee, Christina K.
Sun, Junfeng
Izycka-Swieszewska, Ewa
Toretsky, Jeffrey A.
Kitlinska, Joanna
TI Dipeptidyl Peptidases as Survival Factors in Ewing Sarcoma Family of
Tumors IMPLICATIONS FOR TUMOR BIOLOGY AND THERAPY
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID FIBROBLAST ACTIVATION PROTEIN; APOPTOSIS-INDUCING FACTOR;
NEUROPEPTIDE-Y; SUBSTRATE-SPECIFICITY; POTENTIAL TARGETS; CELL-LINES;
IV; EXPRESSION; CANCER; RECEPTOR
AB Ewing sarcoma family of tumors (ESFT) is a group of aggressive pediatric malignancies driven by the EWS-FLI1 fusion protein, an aberrant transcription factor up-regulating specific target genes, such as neuropeptide Y (NPY) and its Y1 and Y5 receptors (Y5Rs). Previously, we have shown that both exogenous NPY and endogenous NPY stimulate ESFT cell death via its Y1 and Y5Rs. Here, we demonstrate that this effect is prevented by dipeptidyl peptidases (DPPs), which cleave NPY to its shorter form, NPY(3-36), not active at Y1Rs. We have shown that NPY-induced cell death can be abolished by overexpression of DPPs and enhanced by their down-regulation. Both NPY treatment and DPP blockade activated the same cell death pathway mediated by poly(ADP-ribose) polymerase (PARP-1) and apoptosis-inducing factor (AIF). Moreover, the decrease in cell survival induced by DPP inhibition was blocked by Y1 and Y5R antagonists, confirming its dependence on endogenous NPY. Interestingly, similar levels of NPY-driven cell death were achieved by blocking membrane DPPIV and cytosolic DPP8 and DPP9. Thus, this is the first evidence of these intracellular DPPs cleaving releasable peptides, such as NPY, in live cells. In contrast, another membrane DPP, fibroblast activation protein (FAP), did not affect NPY actions. In conclusion, DPPs act as survival factors for ESFT cells and protect them from cell death induced by endogenous NPY. This is the first demonstration that intracellular DPPs are involved in regulation of ESFT growth and may become potential therapeutic targets for these tumors.
C1 [Jeha, Dima; Hanafy, Jailan; Lee, Christina K.; Kitlinska, Joanna] Georgetown Univ, Dept Biochem & Mol & Cellular Biol, Washington, DC 20057 USA.
[Soldin, Steven J.] Georgetown Univ, Dept Pharmacol, Washington, DC 20057 USA.
[Mendu, Damodara R.] Georgetown Univ, Georgetown Howard Univ Ctr Clin & Translat Sci, Washington, DC 20057 USA.
[Toretsky, Jeffrey A.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20057 USA.
[Sun, Junfeng] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Izycka-Swieszewska, Ewa] Med Univ Gdansk, Dept Pathomorphol, PL-80211 Gdansk, Poland.
RP Kitlinska, J (reprint author), 3900 Reservoir Rd NW,Basic Sci Bldg,Rm 231A, Washington, DC 20057 USA.
EM jbk4@georgetown.edu
RI Lu, Congyi/G-3984-2013
FU National Institutes of Health [1RO1CA123211-01]; Children's Cancer
Foundation
FX This work was supported, in whole or in part, by National Institutes of
Health Grant 1RO1CA123211-01 (to J. K.) and funding from the Children's
Cancer Foundation (to J. K.).
NR 49
TC 31
Z9 32
U1 1
U2 9
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 5
PY 2011
VL 286
IS 31
BP 27494
EP 27505
DI 10.1074/jbc.M111.224089
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 799EZ
UT WOS:000293268700044
PM 21680731
ER
PT J
AU Tanaka, H
Senda, M
Venugopalan, N
Yamamoto, A
Senda, T
Ishida, T
Horiike, K
AF Tanaka, Hiroyuki
Senda, Miki
Venugopalan, Nagarajan
Yamamoto, Atsushi
Senda, Toshiya
Ishida, Tetsuo
Horiike, Kihachiro
TI Crystal Structure of a Zinc-dependent D-Serine Dehydratase from Chicken
Kidney
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID AMINO-ACID OXIDASE; PYRIDOXAL-PHOSPHATE ENZYMES; ALANINE RACEMASE;
D-ASPARTATE; REACTION SPECIFICITY; THREONINE ALDOLASE; DIFFRACTION DATA;
PROTEIN; BRAIN; IDENTIFICATION
AB D-Serine is a physiological co-agonist of the N-methyl-D-aspartate receptor. It regulates excitatory neurotransmission, which is important for higher brain functions in vertebrates. In mammalian brains, D-amino acid oxidase degrades D-serine. However, we have found recently that in chicken brains the oxidase is not expressed and instead a D-serine dehydratase degrades D-serine. The primary structure of the enzyme shows significant similarities to those of metal-activated D-threonine aldolases, which are fold-type III pyridoxal 5'-phosphate (PLP)-dependent enzymes, suggesting that it is a novel class of D-serine dehydratase. In the present study, we characterized the chicken enzyme biochemically and also by x-ray crystallography. The enzyme activity on D-serine decreased 20-fold by EDTA treatment and recovered nearly completely by the addition of Zn2+. None of the reaction products that would be expected from side reactions of the PLP-D-serine Schiff base were detected during the >6000 catalytic cycles of dehydration, indicating high reaction specificity. We have determined the first crystal structure of the D-serine dehydratase at 1.9 angstrom resolution. In the active site pocket, a zinc ion that coordinates His(347) and Cys(349) is located near the PLP-Lys(45) Schiff base. A theoretical model of the enzyme-D-serine complex suggested that the hydroxyl group of D-serine directly coordinates the zinc ion, and that the epsilon-NH2 group of Lys(45) is a short distance from the substrate C alpha atom. The alpha-proton abstraction from D-serine by Lys(45) and the elimination of the hydroxyl group seem to occur with the assistance of the zinc ion, resulting in the strict reaction specificity.
C1 [Senda, Toshiya] Natl Inst Adv Ind Sci & Technol, Biomed Informat Res Ctr, Koto Ku, Tokyo 1350064, Japan.
[Tanaka, Hiroyuki; Yamamoto, Atsushi; Ishida, Tetsuo; Horiike, Kihachiro] Shiga Univ Med Sci, Dept Biochem & Mol Biol, Shiga 5202192, Japan.
[Senda, Miki] Japan Biol Informat Consortium, JBIC Res Inst, Struct Guided Drug Dev Project, Koto Ku, Tokyo 1350064, Japan.
[Venugopalan, Nagarajan] NCI, Collaborat Access Team, Biosci Div, Argonne Natl Lab, Argonne, IL 60439 USA.
[Venugopalan, Nagarajan] Natl Inst Gen Med Sci, Argonne, IL 60439 USA.
RP Senda, T (reprint author), Natl Inst Adv Ind Sci & Technol, Biomed Informat Res Ctr, Koto Ku, 2-4-7 Aomi, Tokyo 1350064, Japan.
EM toshiya-senda@aist.go.jp; teishida@belle.shiga-med.ac.jp
FU Ministry of Education, Culture, Sports, Science, and Technology of
Japan; New Energy and Industrial Technology Development Organization of
Japan; Shiga University of Medical Science
FX This work was supported in part by a grant-in-aid for Scientific
Research from the Ministry of Education, Culture, Sports, Science, and
Technology of Japan; by the New Energy and Industrial Technology
Development Organization of Japan; and by a grant-in-aid (Heisei era 22)
from the Shiga University of Medical Science.
NR 42
TC 12
Z9 12
U1 1
U2 17
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 5
PY 2011
VL 286
IS 31
BP 27548
EP 27558
DI 10.1074/jbc.M110.201160
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 799EZ
UT WOS:000293268700049
PM 21676877
ER
PT J
AU Fei, ZL
Bera, TK
Liu, XF
Xiang, LM
Pastan, I
AF Fei, Zhaoliang
Bera, Tapan K.
Liu, Xiufen
Xiang, Laiman
Pastan, Ira
TI Ankrd26 Gene Disruption Enhances Adipogenesis of Mouse Embryonic
Fibroblasts
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID MITOTIC CLONAL EXPANSION; ADIPOCYTE DIFFERENTIATION; PPAR-GAMMA;
TRANSCRIPTIONAL REGULATION; 3T3-L1 PREADIPOCYTES; C/EBP-ALPHA; MAP
KINASE; ACTIVATION; EXPRESSION; CELLS
AB We previously reported that partial disruption of the Ankrd26 gene in mice leads to hyperphagia and leptin-resistant obesity. To determine whether the Ankrd26 mutation can affect the development of adipocytes, we studied mouse embryo fibroblasts (MEFs) from the mutant mice. We found that Ankrd26(-/-) MEFs have a higher rate of spontaneous adipogenesis than normal MEFs and that adipocyte formation is greatly increased when the cells are induced with troglitazone alone or with a mixture of troglitazone, insulin, dexamethasone, and methyl-isobutylxanthine. Increased adipogenesis was detected as an increase in lipid droplet formation and in the expression of several markers of adipogenesis. There was an increase in expression of early stage adipogenesis genes such as Krox20, KLF5, C/EBP beta, C/EBP delta, and late stage adipogenesis regulators KLF15, C/EBP alpha, PPAR gamma, and aP2. There was also an increase in adipocyte stem cell markers CD34 and Sca-1 and preadipocyte markers Gata2 and Pref-1, indicating an increase in both stem cells and progenitor cells in the mutant MEFs. Furthermore, ERK was found constitutively activated in Anrd26(-/-) MEFs, and the addition of MEK inhibitors to mutant cells blocked ERK activation, decreased adipogenesis induction, and significantly reduced expression of C/EBP delta, KLF15, PPAR gamma 2, CD34, and Pref-1 genes. We conclude that Ankrd26 gene disruption promotes adipocyte differentiation at both the progenitor commitment and differentiation steps and that ERK activation plays a role in this process.
C1 [Fei, Zhaoliang; Bera, Tapan K.; Liu, Xiufen; Xiang, Laiman; Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Pastan, I (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Rm 5106, Bethesda, MD 20892 USA.
EM pastani@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX This work was supported, in whole or in part, by the Intramural Research
Program of the National Institutes of Health, National Cancer Institute,
Center for Cancer Research.
NR 32
TC 18
Z9 19
U1 0
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 5
PY 2011
VL 286
IS 31
BP 27761
EP 27768
DI 10.1074/jbc.M111.248435
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 799EZ
UT WOS:000293268700068
PM 21669876
ER
PT J
AU Matendo, R
Engmann, C
Ditekemena, J
Gado, J
Tshefu, A
Kinoshita, R
McClure, EM
Moore, J
Wallace, D
Carlo, WA
Wright, LL
Bose, C
AF Matendo, Richard
Engmann, Cyril
Ditekemena, John
Gado, Justin
Tshefu, Antoinette
Kinoshita, Rinko
McClure, Elizabeth M.
Moore, Janet
Wallace, Dennis
Carlo, Waldemar A.
Wright, Linda L.
Bose, Carl
TI Reduced perinatal mortality following enhanced training of birth
attendants in the Democratic Republic of Congo: a time-dependent effect
SO BMC MEDICINE
LA English
DT Article
ID 4-MILLION NEONATAL DEATHS; ESSENTIAL NEWBORN CARE; SRI-LANKA; IMPACT;
INTERVENTIONS; HOSPITALS; EDUCATION
AB Background: In many developing countries, the majority of births are attended by traditional birth attendants, who lack formal training in neonatal resuscitation and other essential care required by the newly born infant. In these countries, the major causes of neonatal mortality are birth asphyxia, infection, and low-birth-weight/prematurity. Death from these causes is potentially modifiable using low-cost interventions, including neonatal resuscitation training. The purpose of this study was to evaluate the effect on perinatal mortality of training birth attendants in a rural area of the Democratic Republic of Congo (DRC) using two established programs.
Methods: This study, a secondary analysis of DRC-specific data collected during a multi-country study, was conducted in two phases. The effect of training using the WHO Essential Newborn Care (ENC) program was evaluated using an active baseline design, followed by a cluster randomized trial of training using an adaptation of a neonatal resuscitation program (NRP). The perinatal mortality rates before ENC, after ENC training, and after randomization to additional NRP training or continued care were compared. In addition, the influence of time following resuscitation training was investigated by examining change in perinatal mortality during sequential three-month increments following ENC training.
Results: More than two-thirds of deliveries were attended by traditional birth attendants and occurred in homes; these proportions decreased after ENC training. There was no apparent decline in perinatal mortality when the outcome of all deliveries prior to ENC training was compared to those after ENC but before NRP training. However, there was a gradual but significant decline in perinatal mortality during the year following ENC training (RR 0.73; 95% CI: 0.56-0.96), which was independently associated with time following training. The decline was attributable to a decline in early neonatal mortality. NRP training had no demonstrable effect on early neonatal mortality.
Conclusion: Training DRC birth attendants using the ENC program reduces perinatal mortality. However, a period of utilization and re-enforcement of training may be necessary before a decline in mortality occurs. ENC training has the potential to be a low cost, high impact intervention in developing countries.
C1 [Matendo, Richard; Ditekemena, John; Gado, Justin; Tshefu, Antoinette] Kinshasa Sch Publ Hlth, Kinshasa, Zaire.
[Engmann, Cyril; Kinoshita, Rinko; Bose, Carl] Univ N Carolina, Div Neonatal Perinatal Med, Chapel Hill, NC 27599 USA.
[McClure, Elizabeth M.; Moore, Janet; Wallace, Dennis] Res Triangle Inst, Res Triangle Pk, NC 27709 USA.
[Carlo, Waldemar A.] Univ Alabama, Women & Infants Ctr, Birmingham, AL 35233 USA.
[Wright, Linda L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
RP Matendo, R (reprint author), Kinshasa Sch Publ Hlth, Kinshasa, Zaire.
EM rmatendo@yahoo.fr
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development Global Network for Women's and Children's Health Research
[U01 HD043475, U01 HD40636]; Bill and Melinda Gates Foundation
FX This study was funded by the Eunice Kennedy Shriver National Institute
of Child Health and Human Development Global Network for Women's and
Children's Health Research (U01 HD043475; U01 HD40636) and the Bill and
Melinda Gates Foundation.
NR 16
TC 12
Z9 12
U1 0
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1741-7015
J9 BMC MED
JI BMC Med.
PD AUG 4
PY 2011
VL 9
AR 93
DI 10.1186/1741-7015-9-93
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 818OP
UT WOS:000294762800001
PM 21816050
ER
PT J
AU Burbelo, PD
Ching, KH
Esper, F
Iadarola, MJ
Delwart, E
Lipkin, WI
Kapoor, A
AF Burbelo, Peter D.
Ching, Kathryn H.
Esper, Frank
Iadarola, Michael J.
Delwart, Eric
Lipkin, W. Ian
Kapoor, Amit
TI Serological Studies Confirm the Novel Astrovirus HMOAstV-C as a Highly
Prevalent Human Infectious Agent
SO PLOS ONE
LA English
DT Article
ID LUCIFERASE IMMUNOPRECIPITATION SYSTEMS; HUMAN STOOL; CHILDREN; DIARRHEA;
GASTROENTERITIS; IDENTIFICATION; DIAGNOSIS; VIRUS; ASSAY; SEQUENCES
AB Molecular identification of a microbe is the first step in determining its prevalence of infection and pathogenic potential. Detection of specific adaptive immune responses can provide insights into whether a microbe is a human infectious agent and its epidemiology. Here we characterized human anti-IgG antibody responses by luciferase immunoprecipitation systems (LIPS) against two protein fragments derived from the capsid protein of the novel HMOAstV-C astrovirus. While antibodies to the N-terminal fragment were not informative, the C-terminal capsid fragment of HMOAstV-C showed a high frequency of immunoreactivity with serum from healthy blood donors. In contrast, a similar C-terminal capsid fragment from the related HMOAstV-A astrovirus failed to show immunoreactivity. Detailed analysis of adult serum from the United Sates using a standardized threshold demonstrated HMOAstV-C seropositivity in approximately 65% of the samples. Evaluation of serum samples from different pediatric age groups revealed that the prevalence of antibodies in 6-12 month, 1-2 year, 2-5 year and 5-10 year olds was 20%, 23%, 32% and 36%, respectively, indicating rising seroprevalence with age. Additionally, 50% (11/22) of the 0-6 month old children showed anti-HMOAstV-C antibody responses, likely reflecting maternal antibodies. Together these results document human humoral responses to HMOAstV-C and validate LIPS as a facile and effective approach for identifying humoral responses to novel infectious agents.
C1 [Burbelo, Peter D.; Ching, Kathryn H.; Iadarola, Michael J.] Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, NIH, Bethesda, MD USA.
[Esper, Frank] Case Western Reserve Univ Hosp, Med Ctr, Dept Pediat, Cleveland, OH 44106 USA.
[Delwart, Eric] Univ Calif San Francisco, Blood Syst Res Inst, San Francisco, CA 94143 USA.
[Delwart, Eric] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA.
[Lipkin, W. Ian; Kapoor, Amit] Columbia Univ, Ctr Infect & Immun, New York, NY USA.
RP Burbelo, PD (reprint author), Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, NIH, Bethesda, MD USA.
EM burbelop@nidcr.nih.gov
OI Delwart, Eric/0000-0002-6296-4484
FU Division of Intramural Research, National Institute of Dental and
Craniofacial Research; National Institute of Allergy and Infectious
Diseases [K23 AI065829, AI090196, AI57158]; Department of Defense; Blood
Systems Research Institute; NIH [R01220 HL083254]
FX This work was supported by the Division of Intramural Research, National
Institute of Dental and Craniofacial Research. This study is supported
in part by the National Institute of Allergy and Infectious Diseases K23
AI065829 (F.E.), AI090196 (A.K.) and AI57158 (Northeast Biodefense
Center - A.K., W.I.L), and the Department of Defense (A.K., W.I.L.) and
the Blood Systems Research Institute and NIH R01220 HL083254 (E.D.). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript. No additional
external funding received for this study.
NR 32
TC 29
Z9 30
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 4
PY 2011
VL 6
IS 8
AR e22576
DI 10.1371/journal.pone.0022576
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 803DK
UT WOS:000293561200023
PM 21829634
ER
PT J
AU Barrett, AJ
AF Barrett, A. John
TI CMV: when bad viruses turn good
SO BLOOD
LA English
DT Editorial Material
ID BONE-MARROW-TRANSPLANTATION; CYTOMEGALOVIRUS; RELAPSE
C1 NHLBI, Bethesda, MD 20892 USA.
RP Barrett, AJ (reprint author), NHLBI, Bethesda, MD 20892 USA.
NR 7
TC 7
Z9 9
U1 0
U2 3
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 4
PY 2011
VL 118
IS 5
BP 1193
EP 1194
DI 10.1182/blood-2011-06-354340
PG 4
WC Hematology
SC Hematology
GA 802KP
UT WOS:000293510000007
PM 21816840
ER
PT J
AU Hsieh, MM
Fitzhugh, CD
Tisdale, JF
AF Hsieh, Matthew M.
Fitzhugh, Courtney D.
Tisdale, John F.
TI Allogeneic hematopoietic stem cell transplantation for sickle cell
disease: the time is now
SO BLOOD
LA English
DT Article
ID BONE-MARROW-TRANSPLANTATION; CORD BLOOD TRANSPLANTATION; MURINE
BETA-THALASSEMIA; SEVERE COMBINED IMMUNODEFICIENCY; CHRONIC
GRANULOMATOUS-DISEASE; MULTIPLY TRANSFUSED PATIENTS;
VERSUS-HOST-DISEASE; GENE-THERAPY; HEMATOLOGIC MALIGNANCIES; LONG-TERM
AB Although sickle cell disease (SCD) has a variable clinical course, many patients develop end-organ complications that are associated with significant morbidity and early mortality. Myeloablative allogeneic HSCT (allo-HSCT) is curative but has been historically performed only in children younger than 16 years of age. Modest modifications in the conditioning regimen and supportive care have improved outcome such that the majority of children with a suitable HLA-matched sibling donor can expect a cure from this approach. However, adult patients have been excluded from myeloablative allo-HSCT because of anticipated excess toxicity resulting from accumulated disease burden. Efforts to use nonmyeloablative transplantation strategies in adults logically followed but were initially met with largely disappointing results. Recent results, however, indicate that nonmyeloablative allo-HSCT in adult patients with SCD allows for stable mixed hematopoietic chimerism with associated full-donor erythroid engraftment and normalization of blood counts, and persistence in some without continued immunosuppression suggests immunologic tolerance. The attainment of tolerance should allow extension of these potentially curative approaches to alternative donor sources. Efforts to build on these experiences should increase the use of allo-HSCT in patients with SCD while minimizing morbidity and mortality. (Blood. 2011;118(5):1197-1207)
C1 [Hsieh, Matthew M.; Fitzhugh, Courtney D.; Tisdale, John F.] NIDDK, Mol & Clin Hematol Branch, NHLBI, NIH, Bethesda, MD USA.
RP Tisdale, JF (reprint author), 9000 Rockville Pike,Bldg 10 9N 112, Bethesda, MD 20892 USA.
EM johntis@mail.nih.gov
FU National Institutes of Health in the National Heart, Lung, and Blood
Institute; National Institute of Diabetes and Digestive and Kidney
Diseases
FX This work is supported by the intramural research program of the
National Institutes of Health in the National Heart, Lung, and Blood
Institute and the National Institute of Diabetes and Digestive and
Kidney Diseases.
NR 96
TC 50
Z9 51
U1 1
U2 12
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 4
PY 2011
VL 118
IS 5
BP 1197
EP 1207
DI 10.1182/blood-2011-01-332510
PG 11
WC Hematology
SC Hematology
GA 802KP
UT WOS:000293510000010
PM 21628400
ER
PT J
AU Li, XG
Wang, SH
Li, Y
Deng, CW
Steiner, LA
Xiao, H
Wu, C
Bungert, J
Gallagher, PG
Felsenfeld, G
Qiu, Y
Huang, SM
AF Li, Xingguo
Wang, Shaohua
Li, Ying
Deng, Changwang
Steiner, Laurie A.
Xiao, Hua
Wu, Carl
Bungert, Joerg
Gallagher, Patrick G.
Felsenfeld, Gary
Qiu, Yi
Huang, Suming
TI Chromatin boundaries require functional collaboration between the hSET1
and NURF complexes
SO BLOOD
LA English
DT Article
ID REMODELING COMPLEX; HISTONE ACETYLATION; METHYLTRANSFERASE ACTIVITY;
MOLECULAR REGULATION; H3K4 TRIMETHYLATION; PROGENITOR CELLS;
BARRIER-ELEMENT; PHD FINGER; STEM-CELLS; METHYLATION
AB Chromatin insulators protect erythroid genes from being silenced during erythropoiesis, and the disruption of barrier insulator function in erythroid membrane gene loci results in mild or severe anemia. We showed previously that the USF1/2-bound 5'HS4 insulator mediates chromatin barrier activity in the erythroid-specific chicken beta-globin locus. It is currently not known how insulators establish such a barrier. To understand the function of USF1, we purified USF1-associated protein complexes and found that USF1 forms a multiprotein complex with hSET1 and NURF, thus exhibiting histone H3K4 methyltransferase- and ATP-dependent nucleosome remodeling activities, respectively. Both SET1 and NURF are recruited to the 5'HS4 insulator by USF1 to retain the active chromatin structure in erythrocytes. Knock-down of NURF resulted in a rapid loss of barrier activity accompanied by an alteration of nucleosome positioning, increased occupancy of the nucleosome-free linker region at the insulator site, and increased repressive H3K27me3 levels in the vicinity of the HS4 insulator. Furthermore, suppression of SET1 reduced barrier activity, decreased H3K4me2 and acH3K9/K14, and diminished the recruitment of BPTF at several erythroid-specific barrier insulator sites. Therefore, our data reveal a synergistic role of hSET1 and NURF in regulating the USF-bound barrier insulator to prevent erythroid genes from encroachment of heterochromatin. (Blood. 2011; 118(5): 1386-1394)
C1 [Li, Xingguo; Wang, Shaohua; Li, Ying; Deng, Changwang; Bungert, Joerg; Huang, Suming] Univ Florida, Coll Med, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA.
[Steiner, Laurie A.; Gallagher, Patrick G.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
[Xiao, Hua; Wu, Carl] NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Bungert, Joerg] Univ Florida, Coll Med, Genet Inst, Gainesville, FL 32610 USA.
[Felsenfeld, Gary] Natl Inst Diabet & Digest & Kidney Dis, Mol Biol Lab, NIH, Bethesda, MD USA.
[Qiu, Yi] Univ Florida, Coll Med, Dept Anat & Cell Biol, Gainesville, FL 32610 USA.
[Qiu, Yi; Huang, Suming] Univ Florida, Coll Med, Shands Canc Ctr, Gainesville, FL 32610 USA.
RP Huang, SM (reprint author), Univ Florida, Coll Med, Dept Biochem & Mol Biol, POB 103633, Gainesville, FL 32610 USA.
EM sumingh@ufl.edu
FU National Institutes of Health [HL091929, HL091929-01A1S1, HL090589,
HL106184, DK62039, DK52356, DK83389, HL095674]; National Institute of
Diabetes and Digestive and Kidney Diseases; National Cancer Institute,
National Institutes of Health, Bethesda, MD
FX This work was supported by grants from the National Institutes of Health
(HL091929, HL091929-01A1S1, the ARRA administrative supplement, and
HL090589 to S.H.; HL106184 and DK62039 to P.G.G.; DK52356 and DK83389 to
J.B.; and HL095674 to Y.Q.). G.F. and C.W. are supported by the
Intramural Research Programs, National Institute of Diabetes and
Digestive and Kidney Diseases, and the National Cancer Institute,
National Institutes of Health, Bethesda, MD, respectively.
NR 46
TC 20
Z9 21
U1 0
U2 4
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 4
PY 2011
VL 118
IS 5
BP 1386
EP 1394
DI 10.1182/blood-2010-11-319111
PG 9
WC Hematology
SC Hematology
GA 802KP
UT WOS:000293510000032
PM 21653943
ER
PT J
AU Chen, SK
Badea, TC
Hattar, S
AF Chen, S. -K.
Badea, T. C.
Hattar, S.
TI Photoentrainment and pupillary light reflex are mediated by distinct
populations of ipRGCs
SO NATURE
LA English
DT Article
ID RETINAL GANGLION-CELLS; MELANOPSIN-KNOCKOUT MICE; MAMMALIAN RETINA;
MOUSE; RESPONSES; MORPHOLOGY; PHOTORECEPTORS; PROJECTIONS; DIVERSITY;
VISION
AB Intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin and regulate a wide array of light-dependent physiological processes(1-11). Genetic ablation of ipRGCs eliminates circadian photoentrainment and severely disrupts the pupillary light reflex (PLR)(12,13). Here we show that ipRGCs consist of distinct subpopulations that differentially express the Brn3b transcription factor, and can be functionally distinguished. Brn3b-negative M1 ipRGCs innervate the suprachiasmatic nucleus (SCN) of the hypothalamus, whereas Brn3b-positive ipRGCs innervate all other known brain targets, including the olivary pre-tectal nucleus. Consistent with these innervation patterns, selective ablation of Brn3b-positive ipRGCs severely disrupts the PLR, but does not impair circadian photoentrainment. Thus, we find that molecularly distinct subpopulations of M1 ipRGCs, which are morphologically and electrophysiologically similar, innervate different brain regions to execute specific light-induced functions.
C1 [Chen, S. -K.; Hattar, S.] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA.
[Badea, T. C.] NEI, Retinal Circuit Dev & Genet Unit, N NRL, NIH, Bethesda, MD 20892 USA.
[Hattar, S.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21218 USA.
RP Hattar, S (reprint author), Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA.
EM tudor.badea@nih.gov; shattar@jhu.edu
OI CHEN, SHIH-KUO/0000-0002-7921-1358
FU Johns Hopkins University Mouse Tri-Lab; National Institutes of Health
[GM076430]; David and Lucile Packard Foundation; Alfred P. Sloan
Foundation
FX We thank J. Nathans for providing several animal lines
(Brn3bCKOAP, R26IAP and Z/AP) that were crucial
for the completion of this study. We thank J. L. Ecker, who created the
inducible cre line (Opn4CreERT2) we used in this study. We
thank Z. Yang in D. Zack's laboratory for providing the
Brn3bZ-dta mouse line, which was generously provided by the
original laboratory that created this line: W. Klein. We also thank R.
Kuruvilla, H. Zhao, M. Halpern, A. P. Sampath and T. Schmidt for their
careful reading of the manuscript and helpful suggestions and the Johns
Hopkins University Mouse Tri-Lab for support. This work was supported by
the National Institutes of Health grant GM076430 (S. H.), the David and
Lucile Packard Foundation (S. H.), and the Alfred P. Sloan Foundation
(S.H.).
NR 28
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PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD AUG 4
PY 2011
VL 476
IS 7358
BP 92
EP +
DI 10.1038/nature10206
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 801NR
UT WOS:000293447300036
PM 21765429
ER
PT J
AU Alter, G
Heckerman, D
Schneidewind, A
Fadda, L
Kadie, CM
Carlson, JM
Oniangue-Ndza, C
Martin, M
Li, B
Khakoo, SI
Carrington, M
Allen, TM
Altfeld, M
AF Alter, Galit
Heckerman, David
Schneidewind, Arne
Fadda, Lena
Kadie, Carl M.
Carlson, Jonathan M.
Oniangue-Ndza, Cesar
Martin, Maureen
Li, Bin
Khakoo, Salim I.
Carrington, Mary
Allen, Todd M.
Altfeld, Marcus
TI HIV-1 adaptation to NK-cell-mediated immune pressure
SO NATURE
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; NATURAL-KILLER-CELLS; MHC CLASS-I; HLA-B;
INHIBITORY RECEPTOR; VIRAL PEPTIDES; BINDING-SITE; RECOGNITION; KIR3DL1;
RESPONSES
AB Natural killer (NK) cells have an important role in the control of viral infections, recognizing virally infected cells through a variety of activating and inhibitory receptors(1-3). Epidemiological and functional studies have recently suggested that NK cells can also contribute to the control of HIV-1 infection through recognition of virally infected cells by both activating and inhibitory killer immunoglobulin-like receptors (KIRs)(4-7). However, it remains unknown whether NK cells can directly mediate antiviral immune pressure in vivo in humans. Here we describe KIR-associated amino-acid polymorphisms in the HIV-1 sequence of chronically infected individuals, on a population level. We show that these KIR-associated HIV-1 sequence polymorphisms can enhance the binding of inhibitory KIRs to HIV-1-infected CD4(+) T cells, and reduce the antiviral activity of KIR-positive NK cells. These data demonstrate that KIR-positive NK cells can place immunological pressure on HIV-1, and that the virus can evade such NK-cell-mediated immune pressure by selecting for sequence polymorphisms, as was previously described for virus-specific T cells and neutralizing antibodies(8). NK cells might therefore have a previously underappreciated role in contributing to viral evolution.
C1 [Alter, Galit; Schneidewind, Arne; Fadda, Lena; Oniangue-Ndza, Cesar; Li, Bin; Carrington, Mary; Allen, Todd M.; Altfeld, Marcus] Harvard Univ, Ragon Inst MGH MIT & Harvard, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA.
[Heckerman, David; Kadie, Carl M.; Carlson, Jonathan M.] Microsoft Res, Redmond, WA 98053 USA.
[Martin, Maureen; Carrington, Mary] NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Khakoo, Salim I.] Univ London Imperial Coll Sci Technol & Med, Div Med, London W2 1PG, England.
RP Altfeld, M (reprint author), Harvard Univ, Ragon Inst MGH MIT & Harvard, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA.
EM maltfeld@partners.org
RI Allen, Todd/F-5473-2011;
OI Khakoo, Salim/0000-0002-4057-9091
FU National Institutes of Health (NIH)/National Institute of Allergy and
Infectious Diseases [R01 AI067031, PO1 AI074415]; Doris Duke Charitable
Foundation; National Cancer Institute (NIH) [HHSN261200800001E]; NIH,
National Cancer Institute, Center for Cancer Research; Wellcome Trust;
Microsoft Research; Bill & Melinda Gates Foundation; Mark and Lisa
Schwartz Foundation; Phillip T. and Susan M. Ragon Foundation
FX These studies were supported by National Institutes of Health
(NIH)/National Institute of Allergy and Infectious Diseases grants R01
AI067031 (M. A.) and PO1 AI074415 (M. A. and T. M. A.), and by the Doris
Duke Charitable Foundation (M. A.). This project was funded in whole or
in part with federal funds from the National Cancer Institute (NIH)
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. This
research was supported in part by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research. S. I. K. is
a recipient of a Wellcome Trust Senior Clinical Fellowship and M. A. is
a Distinguished Clinical Scientist of the Doris Duke Charitable
Foundation. We thank Microsoft Research, the Bill & Melinda Gates
Foundation, the Mark and Lisa Schwartz Foundation and the Phillip T. and
Susan M. Ragon Foundation for their support.
NR 29
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U1 1
U2 25
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD AUG 4
PY 2011
VL 476
IS 7358
BP 96
EP +
DI 10.1038/nature10237
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 801NR
UT WOS:000293447300037
PM 21814282
ER
PT J
AU Aberle, DR
Adams, AM
Berg, CD
Black, WC
Clapp, JD
Fagerstrom, RM
Gareen, IF
Gatsonis, C
Marcus, PM
Sicks, JD
AF Aberle, Denise R.
Adams, Amanda M.
Berg, Christine D.
Black, William C.
Clapp, Jonathan D.
Fagerstrom, Richard M.
Gareen, Ilana F.
Gatsonis, Constantine
Marcus, Pamela M.
Sicks, JoRean D.
CA Natl Lung Screening Trial Res Team
TI Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic
Screening
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID SOMATIC MUTATIONS; TRIAL; CT; DESIGN; VOLUME; ADENOCARCINOMA;
RECRUITMENT; RISK
AB BACKGROUND
The aggressive and heterogeneous nature of lung cancer has thwarted efforts to reduce mortality from this cancer through the use of screening. The advent of low-dose helical computed tomography (CT) altered the landscape of lung-cancer screening, with studies indicating that low-dose CT detects many tumors at early stages. The National Lung Screening Trial (NLST) was conducted to determine whether screening with low-dose CT could reduce mortality from lung cancer.
METHODS
From August 2002 through April 2004, we enrolled 53,454 persons at high risk for lung cancer at 33 U. S. medical centers. Participants were randomly assigned to undergo three annual screenings with either low-dose CT (26,722 participants) or single-view posteroanterior chest radiography (26,732). Data were collected on cases of lung cancer and deaths from lung cancer that occurred through December 31, 2009.
RESULTS
The rate of adherence to screening was more than 90%. The rate of positive screening tests was 24.2% with low-dose CT and 6.9% with radiography over all three rounds. A total of 96.4% of the positive screening results in the low-dose CT group and 94.5% in the radiography group were false positive results. The incidence of lung cancer was 645 cases per 100,000 person-years (1060 cancers) in the low-dose CT group, as compared with 572 cases per 100,000 person-years (941 cancers) in the radiography group (rate ratio, 1.13; 95% confidence interval [CI], 1.03 to 1.23). There were 247 deaths from lung cancer per 100,000 person-years in the low-dose CT group and 309 deaths per 100,000 person-years in the radiography group, representing a relative reduction in mortality from lung cancer with low-dose CT screening of 20.0% (95% CI, 6.8 to 26.7; P = 0.004). The rate of death from any cause was reduced in the low-dose CT group, as compared with the radiography group, by 6.7% (95% CI, 1.2 to 13.6; P = 0.02).
CONCLUSIONS
Screening with the use of low-dose CT reduces mortality from lung cancer.
C1 [Berg, Christine D.] NCI, Canc Prevent Div, Early Detect Res Grp, Bethesda, MD 20892 USA.
[Aberle, Denise R.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Adams, Amanda M.; Gareen, Ilana F.; Gatsonis, Constantine; Sicks, JoRean D.] Brown Univ, ACRIN Biostat Ctr, Providence, RI 02912 USA.
[Black, William C.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA.
[Clapp, Jonathan D.] Informat Management Serv Inc, Rockville, MD USA.
RP Berg, CD (reprint author), NCI, Canc Prevent Div, Early Detect Res Grp, 6130 Execut Blvd,Suite 3112, Bethesda, MD 20892 USA.
EM bergc@mail.nih.gov
RI Gareen, Ilana/I-2816-2014; Berg , Christine/K-1047-2014;
OI Gareen, Ilana/0000-0002-0457-5595; Blevins,
Meridith/0000-0002-3861-9859; fishman, elliot/0000-0002-2567-1658;
Aberle, Denise/0000-0002-8858-3401
FU National Cancer Institute; National Lung Screening [NCT00047385];
Division of Cancer Treatment and Diagnosis [U01-CA-80098, U01-CA-79778];
Early Detection Research Group and Biometry Research Group, Division of
Cancer Prevention: University of Colorado Denver [N01-CN-25514];
Georgetown University [N01-CN-25522]; Pacific Health Research and
Education Institute [N01-CN-25515]; Henry Ford Health System
[N01-CN-25512]; University of Minnesota [N01-CN-25513]; Washington
University in St. Louis [N01-CN-25516]; University of Pittsburgh
[N01-CN-25511]; University of Utah [N01-CN-25524]; Marshfield Clinic
Research Foundation [N01-CN-25518]; University of Alabama at Birmingham
[N01-CN-75022]; Westat [N01-CN-25476]; Information Management Services
[N02-CN-63300]; Wilex; MELA Sciences; Endocyte; Bayer HealthCare;
Radiological Society of North America
FX Funded by the National Cancer Institute; National Lung Screening Trial
ClinicalTrials.gov number, NCT00047385.; The American College of
Radiology Imaging Network component of the National Lung Screening Trial
(NLST) was funded through grants (U01-CA-80098 and U01-CA-79778) under a
cooperative agreement with the Cancer Imaging Program, Division of
Cancer Treatment and Diagnosis. The Lung Screening Study sites of the
NLST were funded through contracts with the Early Detection Research
Group and Biometry Research Group, Division of Cancer Prevention:
University of Colorado Denver (N01-CN-25514), Georgetown University
(N01-CN-25522), Pacific Health Research and Education Institute
(N01-CN-25515), Henry Ford Health System (N01-CN-25512), University of
Minnesota (N01-CN-25513), Washington University in St. Louis
(N01-CN-25516), University of Pittsburgh (N01-CN-25511), University of
Utah (N01-CN-25524), Marshfield Clinic Research Foundation
(N01-CN-25518), University of Alabama at Birmingham (N01-CN-75022),
Westat (N01-CN-25476), and Information Management Services
(N02-CN-63300).; Mr. Clapp reports holding a financial interest in Human
Genome Sciences; and Dr. Gatsonis, receiving consulting fees from Wilex,
MELA Sciences, and Endocyte, lecture fees from Bayer HealthCare, and
support from the Radiological Society of North America for developing
educational presentations. No other potential conflict of interest
relevant to this article was reported.
NR 37
TC 2023
Z9 2067
U1 19
U2 170
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD AUG 4
PY 2011
VL 365
IS 5
BP 395
EP 409
DI 10.1056/NEJMoa1102873
PG 15
WC Medicine, General & Internal
SC General & Internal Medicine
GA 801NW
UT WOS:000293447800004
ER
PT J
AU Scheinberg, P
Nunez, O
Weinstein, B
Scheinberg, P
Biancotto, A
Wu, CO
Young, NS
AF Scheinberg, Phillip
Nunez, Olga
Weinstein, Barbara
Scheinberg, Priscila
Biancotto, Angelique
Wu, Colin O.
Young, Neal S.
TI Horse versus Rabbit Antithymocyte Globulin in Acquired Aplastic Anemia
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID COLONY-STIMULATING FACTOR; ANTI-THYMOCYTE GLOBULIN; REGULATORY T-CELLS;
BONE-MARROW-TRANSPLANTATION; IMMUNOSUPPRESSIVE THERAPY; ANTILYMPHOCYTE
GLOBULIN; LYMPHOCYTE GLOBULIN; CYCLOSPORINE; ATG; THYMOGLOBULIN
AB BACKGROUND
In severe acquired aplastic anemia, hematopoietic failure is the result of immune-mediated destruction of bone marrow stem and progenitor cells. Immunosuppressive therapy with antithymocyte globulin (ATG) plus cyclosporine is an effective alternative to stem-cell transplantation and improves blood counts and survival. Although horse ATG is the standard therapy, rabbit ATG is more potent in depleting peripheral-blood lymphocytes and is preferred in other clinical circumstances.
METHODS
From December 2005 through July 2010, we performed a randomized trial comparing these two ATG formulations in conventional regimens. Patients were treated at a single facility. The primary outcome was hematologic response at 6 months, as determined by blood counts. The study was designed to enroll 60 patients each for the rabbit-ATG and horse-ATG groups and was powered to detect a difference of 25 percentage points in the response rate.
RESULTS
A large, unexpected difference was observed in the rate of hematologic response at 6 months in favor of horse ATG (68%; 95% confidence interval [CI], 56 to 80) as compared with rabbit ATG (37%; 95% CI, 24 to 49; P < 0.001). Overall survival at 3 years also differed, with a survival rate of 96% (95% CI, 90 to 100) in the horse-ATG group as compared with 76% (95% CI, 61 to 95) in the rabbit-ATG group (P =0.04) when data were censored at the time of stem-cell transplantation, and 94% (95% CI, 88 to 100) as compared with 70% (95% CI, 56 to 86; P=0.008) in the respective groups when stem-cell-transplantation events were not censored.
CONCLUSIONS
In a randomized study, rabbit ATG was inferior to horse ATG as a first treatment for severe aplastic anemia, as indicated by hematologic response and survival.
C1 [Scheinberg, Phillip; Nunez, Olga; Weinstein, Barbara; Scheinberg, Priscila; Young, Neal S.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA.
[Wu, Colin O.] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
[Biancotto, Angelique; Young, Neal S.] NIH, Trans NIH Ctr Human Immunol Auto Immunol & Inflam, Bethesda, MD 20892 USA.
RP Scheinberg, P (reprint author), 10 Ctr Dr,Bldg 10 CRC,Rm 3E-5140,MSC 1202, Bethesda, MD 20892 USA.
EM scheinbp@mail.nih.gov; scheinbp@mail.nih.gov
OI Scheinberg, Phillip/0000-0002-9047-4538
FU National Institutes of Health [NCT00260689]; National Heart, Lung, and
Blood Institute, National Institutes of Health
FX Funded by the Intramural Research Program of the National Institutes of
Health; ClinicalTrials.gov number, NCT00260689.; Supported by the
Intramural Research Program of the National Heart, Lung, and Blood
Institute, National Institutes of Health.
NR 32
TC 125
Z9 140
U1 0
U2 6
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD AUG 4
PY 2011
VL 365
IS 5
BP 430
EP 438
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 801NW
UT WOS:000293447800007
PM 21812672
ER
PT J
AU Jo, J
Kilimnik, G
Kim, A
Guo, C
Periwal, V
Hara, M
AF Jo, Junghyo
Kilimnik, German
Kim, Abraham
Guo, Charles
Periwal, Vipul
Hara, Manami
TI Formation of Pancreatic Islets Involves Coordinated Expansion of Small
Islets and Fission of Large Interconnected Islet-like Structures
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID BETA-CELL MASS; POLYCLONAL ORIGIN; TRANSGENIC MICE; MOUSE PANCREAS;
ADULT-RATS; IN-SITU; GROWTH; QUANTIFICATION; REGENERATION; PROGENITORS
AB The islets of Langerhans, micro-organs for maintaining glucose homeostasis, range in size from small clusters of < 10 cells to large islets consisting of several thousand endocrine cells. Islet size distributions among various species are similar and independent of body size, suggesting an intrinsic limit to islet size. Little is known about the mechanisms regulating islet size. We have carried out a comprehensive analysis of changes of islet size distribution in the intact mouse pancreas from birth to eight months, including mathematical modeling to quantify this dynamic biological process. Islet growth was size-dependent during development, with preferential expansion of smaller islets and fission of large interconnected islet-like structures occurring most actively at approximately three weeks of age at the time of weaning. The process of islet formation was complete by four weeks with little or no new islet formation thereafter, and all the beta-cells had low proliferation potential in the adult, regardless of islet size. Similarly, in insulinoma-bearing mice, the early postnatal developmental process including fission followed the same time course with no new islet formation in adults. However, tumor progression led to uncontrolled islet growth with accelerated expansion of larger islets. Thus, islet formation and growth is a tightly regulated process involving preferential expansion of small islets and fission of large interconnected islet-like structures.
C1 [Jo, Junghyo; Periwal, Vipul] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
[Kilimnik, German; Kim, Abraham; Guo, Charles; Hara, Manami] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
RP Jo, J (reprint author), NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
EM jojunghyo@mail.nih.gov; vipulp@niddk.nih.gov; mhara@midway.uchicago.edu
RI Jo, Junghyo/D-4889-2011; Periwal, Vipul/I-1728-2012
FU U.S. Public Health Service [DK-081527, DK-072473, DK-20595]; National
Institutes of Health, National Institute of Diabetes and Digestive and
Kidney Diseases
FX The study is supported by U.S. Public Health Service DK-081527,
DK-072473, and DK-20595 to The University of Chicago Diabetes Research
and Training Center (Animal Models Core), a gift from the Kovler Family
Foundation, and funding from the intramural research program of the
National Institutes of Health, National Institute of Diabetes and
Digestive and Kidney Diseases.
NR 37
TC 16
Z9 16
U1 0
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
J9 BIOPHYS J
JI Biophys. J.
PD AUG 3
PY 2011
VL 101
IS 3
BP 565
EP 574
DI 10.1016/j.bpj.2011.06.042
PG 10
WC Biophysics
SC Biophysics
GA 804SA
UT WOS:000293673100009
PM 21806924
ER
PT J
AU Wiench, M
John, S
Baek, S
Johnson, TA
Sung, MH
Escobar, T
Simmons, CA
Pearce, KH
Biddie, SC
Sabo, PJ
Thurman, RE
Stamatoyannopoulos, JA
Hager, GL
AF Wiench, Malgorzata
John, Sam
Baek, Songjoon
Johnson, Thomas A.
Sung, Myong-Hee
Escobar, Thelma
Simmons, Catherine A.
Pearce, Kenneth H.
Biddie, Simon C.
Sabo, Pete J.
Thurman, Robert E.
Stamatoyannopoulos, John A.
Hager, Gordon L.
TI DNA methylation status predicts cell type-specific enhancer activity
SO EMBO JOURNAL
LA English
DT Article
DE DNA methylation; DNaseI hypersensitivity; enhancer; glucocorticoid
receptor; tissue specificity
ID TISSUE-SPECIFIC ENHANCERS; NUCLEAR RECEPTOR FUNCTION; EMBRYONIC
STEM-CELLS; GLUCOCORTICOID-RECEPTOR; HUMAN GENOME; CHROMATIN-STRUCTURE;
ACCESSIBLE CHROMATIN; CPG DINUCLEOTIDES; GENE-EXPRESSION; PROMOTER DNA
AB Cell-selective glucocorticoid receptor (GR) binding to distal regulatory elements is associated with cell type-specific regions of locally accessible chromatin. These regions can either pre-exist in chromatin (pre-programmed) or be induced by the receptor (de novo). Mechanisms that create and maintain these sites are not well understood. We observe a global enrichment of CpG density for pre-programmed elements, and implicate their demethylated state in the maintenance of open chromatin in a tissue-specific manner. In contrast, sites that are actively opened by GR (de novo) are characterized by low CpG density, and form a unique class of enhancers devoid of suppressive effect of agglomerated methyl-cytosines. Furthermore, treatment with glucocorticoids induces rapid changes in methylation levels at selected CpGs within de novo sites. Finally, we identify GR-binding elements with CpGs at critical positions, and show that methylation can affect GR-DNA interactions in vitro. The findings present a unique link between tissue-specific chromatin accessibility, DNA methylation and transcription factor binding and show that DNA methylation can be an integral component of gene regulation by nuclear receptors. The EMBO Journal (2011) 30, 3028-3039. doi:10.1038/emboj.2011.210; Published online 24 June 2011
C1 [Wiench, Malgorzata; John, Sam; Baek, Songjoon; Johnson, Thomas A.; Sung, Myong-Hee; Escobar, Thelma; Biddie, Simon C.; Hager, Gordon L.] NCI, Ctr Canc Res, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
[Simmons, Catherine A.; Pearce, Kenneth H.] GlaxoSmithKline Mol Discovery Res, Res Triangle Pk, NC USA.
[Sabo, Pete J.; Thurman, Robert E.; Stamatoyannopoulos, John A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
RP Hager, GL (reprint author), NCI, Ctr Canc Res, Lab Receptor Biol & Gene Express, NIH, Bldg 41,Room B602,41 Lib Dr, Bethesda, MD 20892 USA.
EM hagerg@exchange.nih.gov
OI Biddie, Simon/0000-0002-8253-0253
FU NIH, National Cancer Institute, Center for Cancer Research
FX We thank Yamini Dalal, Tina Miranda, Tom Misteli, Ty Voss and Sam Clokie
for critical discussions and reading of the manuscript. We acknowledge
Anindya Indrawan for technical support and Katherine McKinnon and the
NCI Vaccine Branch FACS Core facility for the assistance with the
cell-cycle analysis. This research was supported by Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research.
NR 63
TC 98
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U1 0
U2 19
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0261-4189
J9 EMBO J
JI Embo J.
PD AUG 3
PY 2011
VL 30
IS 15
BP 3028
EP 3039
DI 10.1038/emboj.2011.210
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 808IG
UT WOS:000293970800007
PM 21701563
ER
PT J
AU Subramanian, J
AF Subramanian, Jaichandar
TI Homeostatic Plasticity of Neurotransmitter Release Probability Is
Determined by Presynaptic Calcium Influx
SO JOURNAL OF NEUROSCIENCE
LA English
DT Editorial Material
C1 NIMH, Unit Behav Genet, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA.
RP Subramanian, J (reprint author), NIMH, Unit Behav Genet, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA.
EM jaichandar@gmail.com
FU Intramural NIH HHS
NR 8
TC 0
Z9 0
U1 0
U2 0
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD AUG 3
PY 2011
VL 31
IS 31
BP 11097
EP 11099
DI 10.1523/JNEUROSCI.2734-11.2011
PG 3
WC Neurosciences
SC Neurosciences & Neurology
GA 801RZ
UT WOS:000293459400001
PM 21813670
ER
PT J
AU Ng, L
Lu, AL
Swaroop, A
Sharlin, DS
Swaroop, A
Forrest, D
AF Ng, Lily
Lu, Ailing
Swaroop, Alok
Sharlin, David S.
Swaroop, Anand
Forrest, Douglas
TI Two Transcription Factors Can Direct Three Photoreceptor Outcomes from
Rod Precursor Cells in Mouse Retinal Development
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID CONE OPSIN EXPRESSION; THYROID-HORMONE RECEPTOR; FATE DETERMINATION;
VERTEBRATE RETINA; MAMMALIAN RETINA; KNOCKOUT MOUSE; COLOR-VISION; NRL;
PROTEIN; BETA
AB The typical mammalian visual system is based upon three photoreceptor types: rods for dim light vision and two types of cones (M and S) for color vision in daylight. However, the process that generates photoreceptor diversity and the cell type in which diversity arises remain unclear. Mice deleted for thyroid hormone receptor beta 2 (TR beta 2) and neural retina leucine zipper factor (NRL) lack M cones and rods, respectively, but gain S cones. We therefore tested the hypothesis that NRL and TR beta 2 direct a common precursor to a rod, M cone, or S cone outcome using Nrl(b2/b2) "knock-in" mice that express TR beta 2 instead of NRL from the endogenous Nrl gene. Nrl(b2/b2) mice lacked rods and produced excess M cones in contrast to the excess S cones in Nrl(-/-) mice. Notably, the presence of both factors yielded rods in Nrl(+/b2) mice. The results demonstrate innate plasticity in postmitotic rod precursors that allows these cells to form three functional photoreceptor types in response to NRL or TR beta 2. We also detected precursor cells in normal embryonic retina that transiently co-expressed Nrl and TR beta 2, suggesting that some precursors may originate in a plastic state. The plasticity of the precursors revealed in Nrl(b2/b2) mice suggests that a two-step transcriptional switch can direct three photoreceptor fates: first, rod versus cone identity dictated by NRL, and second, if NRL fails to act, M versus S cone identity dictated by TR beta 2.
C1 [Ng, Lily; Lu, Ailing; Swaroop, Alok; Sharlin, David S.; Forrest, Douglas] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA.
[Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
RP Forrest, D (reprint author), NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA.
EM forrestd@niddk.nih.gov
OI Swaroop, Anand/0000-0002-1975-1141
FU NIH at NIDDK; NEI
FX This work was supported by the NIH intramural research program at NIDDK
and NEI. We thank M. Ma and J. Nellissery for assistance, W. Wood and E.
C. Ridgway for plasmids, T. F. Davies for Tshr-/- mice, and
E. N. Pugh Jr and R. Bush for advice on ERG analyses.
NR 49
TC 34
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U1 0
U2 6
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD AUG 3
PY 2011
VL 31
IS 31
BP 11118
EP 11125
DI 10.1523/JNEUROSCI.1709-11.2011
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 801RZ
UT WOS:000293459400004
PM 21813673
ER
PT J
AU Reisz, JA
Zink, CN
King, SB
AF Reisz, Julie A.
Zink, Charles N.
King, S. Bruce
TI Rapid and Selective Nitroxyl (HNO) Trapping by Phosphines: Kinetics and
New Aqueous Ligations for HNO Detection and Quantitation
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID CARDIAC SARCOPLASMIC-RETICULUM; DETERRENT AGENT CYANAMIDE; NITRIC-OXIDE
FORMATION; S-NITROSOTHIOLS; ALDEHYDE DEHYDROGENASE; RYANODINE RECEPTORS;
CA2+ RELEASE; ANGELIS SALT; ANION; OXIDATION
AB Recent studies distinguish the biological and pharmacological effects of nitroxyl (HNO) from its oxidized/deprotonated product nitric oxide (center dot NO), but the lack of HNO detection methods limits the understanding its in vivo mechanisms and the identification of endogenous sources. We previously demonstrated that reaction of HNO with triarylphosphines provides aza-ylides and HNO-derived amides, which may serve as stable HNO biomarkers. We now report a kinetic analysis for the trapping of HNO by phosphines, ligations of enzyme-generated HNO, and compatibility studies illustrating the selectivity of phosphines for HNO over other physiologically relevant nitrogen oxides. Quantification of HNO using phosphines is demonstrated using an HPLC-based assay and ligations of phosphine carbamates generate HNO-derived ureas. These results further demonstrate the potential of phosphine probes for reliable biological detection and quantification of HNO.
C1 [Reisz, Julie A.; King, S. Bruce] Wake Forest Univ, Dept Chem, Winston Salem, NC 27109 USA.
[Zink, Charles N.] NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA.
RP King, SB (reprint author), Wake Forest Univ, Dept Chem, Winston Salem, NC 27109 USA.
EM kingsb@wfu.edu
FU NIH [HL 062198, R21 087891]; NSF [CHE-9708077]; North Carolina
Biotechnology Center [9703-IDG-1007]; NIH, National Cancer Institute,
Center for Cancer Research
FX This work was supported by the NIH (HL 062198 and R21 087891, S.B.K),
and the Bruker NMR spectrometers used in this work were purchased with
partial support from the NSF (CHE-9708077) and North Carolina
Biotechnology Center (9703-IDG-1007). JAR and S.B.K. kindly thank Dr.
Marcus Wright (Wake Forest University) for helpful discussion regarding
NMR kinetics studies. This work was supported in part by the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research. C.N.Z. thanks Dr. Sergey Tarasov and Ms. Marzena A.
Dyba of the Biophysics Resource in the Structural Biophysics Laboratory,
NCI-Frederick, and Dr. Ryan Holland in the Laboratory of Chemical
Carcinogenesis, NCI-Frederick, for assistance with the high resolution
mass spectrometry studies and Mr. John R. Klose in the Laboratory of
Proteomics and Analytical Technologies for assistance with the
31P NMR experiments.
NR 67
TC 51
Z9 51
U1 3
U2 27
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD AUG 3
PY 2011
VL 133
IS 30
BP 11675
EP 11685
DI 10.1021/ja203652z
PG 11
WC Chemistry, Multidisciplinary
SC Chemistry
GA 807DA
UT WOS:000293872800048
PM 21699183
ER
PT J
AU Churchyard, GJ
Morgan, C
Adams, E
Hural, J
Graham, BS
Moodie, Z
Grove, D
Gray, G
Bekker, LG
McElrath, MJ
Tomaras, GD
Goepfert, P
Kalams, S
Baden, LR
Lally, M
Dolin, R
Blattner, W
Kalichman, A
Figueroa, JP
Pape, J
Schechter, M
Defawe, O
De Rosa, SC
Montefiori, DC
Nabel, GJ
Corey, L
Keefer, MC
AF Churchyard, Gavin J.
Morgan, Cecilia
Adams, Elizabeth
Hural, John
Graham, Barney S.
Moodie, Zoe
Grove, Doug
Gray, Glenda
Bekker, Linda-Gail
McElrath, M. Juliana
Tomaras, Georgia D.
Goepfert, Paul
Kalams, Spyros
Baden, Lindsey R.
Lally, Michelle
Dolin, Raphael
Blattner, William
Kalichman, Artur
Figueroa, J. Peter
Pape, Jean
Schechter, Mauro
Defawe, Olivier
De Rosa, Stephen C.
Montefiori, David C.
Nabel, Gary J.
Corey, Lawrence
Keefer, Michael C.
CA NIAID HIV Vaccine Trials Network
TI A Phase IIA Randomized Clinical Trial of a Multiclade HIV-1 DNA Prime
Followed by a Multiclade rAd5 HIV-1 Vaccine Boost in Healthy Adults
(HVTN204)
SO PLOS ONE
LA English
DT Article
ID T-CELL RESPONSES; CANDIDATE VACCINE; IMMUNOGENICITY EVALUATION;
INFECTION; ANTIBODY; IMMUNITY; STEP; THAILAND; MONKEYS; SAFETY
AB Background: The safety and immunogenicity of a vaccine regimen consisting of a 6-plasmid HIV-1 DNA prime (envA, envB, envC, gagB, polB, nefB) boosted by a recombinant adenovirus serotype-5 (rAd5) HIV-1 with matching inserts was evaluated in HIV-seronegative participants from South Africa, United States, Latin America and the Caribbean.
Methods: 480 participants were evenly randomized to receive either: DNA (4 mg IM by Biojector) at 0, 1 and 2 months, followed by rAd5 (10(10) PU IM by needle/syringe) at 6 months; or placebo. Participants were monitored for reactogenicity and adverse events throughout the 12-month study. Peak and duration of HIV-specific humoral and cellular immune responses were evaluated after the prime and boost.
Results: The vaccine was well tolerated and safe. T-cell responses, detected by interferon-gamma (IFN-gamma) ELISpot to global potential T-cell epitopes (PTEs) were observed in 70.8% (136/192) of vaccine recipients overall, most frequently to Gag (54.7%) and to Env (54.2%). In U.S. vaccine recipients T-cell responses were less frequent in Ad5 sero-positive versus seronegative vaccine recipients (62.5% versus 85.7% respectively, p = 0.035). The frequency of HIV-specific CD4+ and CD8+ T-cell responses detected by intracellular cytokine staining were similar (41.8% and 47.2% respectively) and most secreted >= 2 cytokines. The vaccine induced a high frequency (83.7%-94.6%) of binding antibody responses to consensus Group M, and Clades A, B and C gp140 Env oligomers. Antibody responses to Gag were elicited in 46% of vaccine recipients.
Conclusion: The vaccine regimen was well-tolerated and induced polyfunctional CD4+ and CD8+ T-cells and multi-clade anti-Env binding antibodies.
C1 [Churchyard, Gavin J.] Aurum Inst Hlth Res, Klerksdorp, South Africa.
[Churchyard, Gavin J.] Univ KwaZulu Natal, CAPRISA, Durban, South Africa.
[Morgan, Cecilia; Hural, John; Moodie, Zoe; Grove, Doug; McElrath, M. Juliana; Defawe, Olivier; De Rosa, Stephen C.; Corey, Lawrence] Fred Hutchinson Canc Res Ctr, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA 98104 USA.
[Adams, Elizabeth] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA.
[Graham, Barney S.; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Gray, Glenda] Univ Witwatersrand, Perinatal HIV Res Unit, Johannesburg, South Africa.
[Bekker, Linda-Gail] Univ Cape Town, Desmond Tutu HIV Fdn, ZA-7925 Cape Town, South Africa.
[Tomaras, Georgia D.] Duke Univ, Med Ctr, Durham, NC USA.
[Goepfert, Paul] Univ Alabama, Birmingham, AL USA.
[Kalams, Spyros] Vanderbilt Univ, Nashville, TN USA.
[Baden, Lindsey R.] Harvard Brigham & Womens Hosp, Boston, MA USA.
[Lally, Michelle] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA.
[Lally, Michelle] Miriam Hosp, Providence, RI 02906 USA.
[Dolin, Raphael] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
[Blattner, William] Univ Maryland, College Pk, MD 20742 USA.
[Kalichman, Artur] Coordenacao Inst Pesquisa, Ctr Referencia & Treinamento DST AIDS, Sao Paulo, Brazil.
[Figueroa, J. Peter] ERTU, Kingston, Jamaica.
[Pape, Jean] Inst Natl Lab & Rech, Cornell GHESKIO, Port Au Prince, Haiti.
[Schechter, Mauro] Univ Fed Rio de Janeiro, Hosp Escola Sao Francisco de Assis, Projeto Praca Onze, Rio De Janeiro, Brazil.
[Montefiori, David C.] Duke Univ, Sch Med, Duke Human Vaccine Inst, Durham, NC USA.
[Keefer, Michael C.] Univ Rochester, Sch Med & Dent, Dept Med, Rochester, NY 14642 USA.
RP Churchyard, GJ (reprint author), Aurum Inst Hlth Res, Klerksdorp, South Africa.
EM gchurchyard@auruminstitute.org
RI Lally, Michelle/I-4865-2016; Tomaras, Georgia/J-5041-2016
OI Lally, Michelle/0000-0003-0716-4668;
FU National Institutes of Health (NIH) [AI046747/AI068614,
AI046703/AI068635, AI046725/AI068618, AI047996/AI069452,
AI048001/AI069447, AI048023/AI069412, AI047980/AI069511,
AI047985/AI069439, AI046747, AI069420, AI069409, AI069469, AI069519,
AI069414, AI069453, 30022/1U01AI069421/U01AI046747]; NIH Division of
AIDS; VRC
FX This study was funded by grants from the National Institutes of Health
(NIH) to the following respective institutions: AI046747/AI068614 (HVTN
Core); AI046703/AI068635 (HVTN SCHARP); AI046725/AI068618 (HVTN
Laboratory program); AI047996/AI069452 (University of Alabama at
Birmingham); AI048001/AI069447 (University of Maryland Baltimore);
AI048023/AI069412 (Brigham and Women's Hospital, Miriam Hospital);
AI047980/AI069511 (University of Rochester); AI047985/AI069439
(Vanderbilt University); AI046747 (Centro de Referencia e
Treinamento-DST/AIDS, ERTU, Klerksdorp, Desmond Tutu HIV Center at Cape
Town, Hospital Escola Sao Francisco de Assi, and Perinatal HIV Research
Unit); AI069420 (Centro de Referencia e Treinamento-DST/AIDS); AI069409
Epidemiology Research and Training Unit (ERTU); AI069469 (Klerksdorp);
AI069519 (Desmond Tutu HIV Center); AI069414 (Hospital Escola Sao
Francisco de Assi); AI069453 (Perinatal HIV Research Unit);
30022/1U01AI069421/U01AI046747 (GHESKIO). The funders provided input
into the study design, analysis and preparation of the manuscript
through the Vaccine Research Center, National Institute of Allergy and
Infectious Diseases (NIAID), and (NIH).; We thank the NIH Division of
AIDS and the VRC for their support during the conduct of the study. We
thank all the study participants and the following research staff are
gratefully acknowledged for their contribution to the successful conduct
of this study: Mhorag Hay, Catherine Bunce, Xia Jin, Jane Kleinjan,
Lizanne Noble, Robert Tucker, Michael Seaman, Julie O'Reilly, Lynne
Kasiske, Patrick Fisher, Monica Barbosa de Souza, Carina Beppu Yoshida,
Maria de Fatima Melo, Daniel Garcia Pereira Neto, Paulo Cesar Hammes,
Jose Claudio Faulhaber, Ana Lucia Weinstein, Sandra Regina Barros
Telles, Narda Nery Tebet, Mary Latka, Mampedi Bogoshi, Joseph
Mohlakoana, Kathy Mngadi, Tanya Nielson, Sirlene Caminada, Gabriela
Junqueira Calazans, Surita Roux, Eftyhia Vardas, Guy De Bruyn.
NR 32
TC 68
Z9 70
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 3
PY 2011
VL 6
IS 8
AR e21225
DI 10.1371/journal.pone.0021225
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 803CQ
UT WOS:000293558900004
PM 21857901
ER
PT J
AU Shumay, E
Chen, J
Fowler, JS
Volkow, ND
AF Shumay, Elena
Chen, John
Fowler, Joanna S.
Volkow, Nora D.
TI Genotype and Ancestry Modulate Brain's DAT Availability in Healthy
Humans
SO PLOS ONE
LA English
DT Article
ID DOPAMINE TRANSPORTER GENE; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER;
DEFICIT HYPERACTIVITY DISORDER; STRIATAL D2 RECEPTORS; VARIABLE NUMBER;
TANDEM REPEATS; IN-VIVO; ADHD; VNTR; POLYMORPHISMS
AB The dopamine transporter (DAT) is a principal regulator of dopaminergic neurotransmission and its gene (the SLC6A3) is a strong biological candidate gene for various behavioral- and neurological disorders. Intense investigation of the link between the SLC6A3 polymorphisms and behavioral phenotypes yielded inconsistent and even contradictory results. Reliance on objective brain phenotype measures, for example, those afforded by brain imaging, might critically improve detection of DAT genotype-phenotype association. Here, we tested the relationship between the DAT brain availability and the SLC6A3 genotypes using an aggregate sample of 95 healthy participants of several imaging studies. These studies employed positron emission tomography (PET) with [(11)C] cocaine wherein the DAT availability was estimated as Bmax/Kd; while the genotype values were obtained on two repeat polymorphisms -3-UTR- and intron 8-VNTRs. The main findings are the following: 1) both polymorphisms analyzed as single genetic markers and in combination (haplotype) modulate DAT density in midbrain; 2) ethnic background and age influence the strength of these associations; and 3) age-related changes in DAT availability differ in the 3-UTR and intron8 - genotype groups.
C1 [Shumay, Elena; Fowler, Joanna S.] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
[Chen, John] SUNY Stony Brook, Dept Prevent Med, Stony Brook, NY 11794 USA.
[Volkow, Nora D.] Natl Inst Drug Abuse, NIH, Bethesda, MD USA.
RP Shumay, E (reprint author), Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
EM eshumay@bnl.gov
FU National Institute on Drug Abuse [KO1 DA025280-01A1, K05 DA20001];
National Institutes of Health, NIDA
FX This work was performed at Brookhaven National Laboratory with
infrastructure support from the Department of Energy, Office of
Biological and Environmental Research and funded by the National
Institute on Drug Abuse, grants KO1 DA025280-01A1 (ES), K05 DA20001
(JSF) and National Institutes of Health Intramural Research Program,
NIDA (NDV). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 70
TC 31
Z9 31
U1 1
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 3
PY 2011
VL 6
IS 8
AR e22754
DI 10.1371/journal.pone.0022754
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 803CQ
UT WOS:000293558900029
PM 21826203
ER
PT J
AU Bergin, PF
Doppelts, JD
Kephart, CJ
Benke, MT
Graeter, JH
Holmes, AS
Haleem-Smith, H
Tuan, RS
Unger, AS
AF Bergin, Patrick F.
Doppelts, Jason D.
Kephart, Curtis J.
Benke, Michael T.
Graeter, James H.
Holmes, Andrew S.
Haleem-Smith, Hana
Tuan, Rocky S.
Unger, Anthony S.
TI Comparison of Minimally Invasive Direct Anterior Versus Posterior Total
Hip Arthroplasty Based on Inflammation and Muscle Damage Markers
SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME
LA English
DT Article
ID TOTAL KNEE ARTHROPLASTY; SERUM CREATINE-KINASE; ACUTE-PHASE RESPONSE;
MINI-INCISION; OUTCOMES; REPLACEMENT; ORIENTATION; DISLOCATION;
2-INCISION; FRACTURES
AB Background: A number of surgical approaches are utilized in total hip arthroplasty. It has been hypothesized that the anterior approach results in less muscle damage than the posterior approach. We prospectively analyzed biochemical markers of muscle damage and inflammation in patients treated with minimally invasive total hip arthroplasty with an anterior or posterior approach to provide objective evidence of the local soft-tissue injury at the time of arthroplasty.
Methods: Twenty-nine patients treated with minimally invasive total hip arthroplasty through a direct anterior approach and twenty-eight patients treated with the same procedure through a posterior approach were prospectively analyzed. Perioperative and radiographic data were collected to ensure cohorts with similar characteristics. Serum creatine kinase (CK), C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-1 beta (IL-18), and tumor necrosis factor-alpha (TNF-alpha) levels were measured preoperatively, in the post-anesthesia-care unit (except for the CRP level), and on postoperative days 1 and 2. The Student t test and Fisher exact test were used to make comparisons between the two groups. Independent predictors of elevation in levels of markers of inflammation and muscle damage were determined with use of multivariate logistic regression analysis.
Results: The levels of the markers of inflammation were slightly decreased in the direct-anterior-approach group as compared with those in the posterior-approach group. The rise in the CK level in the posterior-approach group was 5.5 times higher than that in the anterior-approach group in the post-anesthesia-care unit (mean difference, 150.3 units/L [95% CI, 70.4 to 230.2]; p < 0.05) and nearly twice as high cumulatively (mean difference, 305.0 units/L [95% CI, -46.7 to 656.8]; p < 0.05).
Conclusions: We believe that the anterior total hip arthroplasty approach used in this study caused significantly less muscle damage than did the posterior surgical approach, as indicated by serum CK levels. The clinical importance of the rise in the CK level needs to be delineated by additional clinical studies. The overall physiologic burden, as demonstrated by measurement of inflammation marker levels, appears to be similar between the anterior and posterior approaches. Objective measurement of muscle damage and inflammation markers provides an unbiased way of determining the immediate effects of surgical intervention, in patients treated with total hip arthroplasty.
C1 George Washington Univ, Dept Orthopaed Surg, Washington, DC 20037 USA.
NIH, Washington, DC USA.
RP Bergin, PF (reprint author), Univ Mississippi, Med Ctr, Dept Orthopaed Surg, 2500 N State St, Jackson, MS 39216 USA.
EM patbergin@gmail.com
NR 29
TC 62
Z9 66
U1 2
U2 11
PU JOURNAL BONE JOINT SURGERY INC
PI NEEDHAM
PA 20 PICKERING ST, NEEDHAM, MA 02192 USA
SN 0021-9355
J9 J BONE JOINT SURG AM
JI J. Bone Joint Surg.-Am. Vol.
PD AUG 3
PY 2011
VL 93A
IS 15
BP 1392
EP 1398
DI 10.2106/JBJS.J.00557
PG 7
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 805JM
UT WOS:000293722700003
PM 21915544
ER
PT J
AU Birkenfeld, AL
Lee, HY
Guebre-Egziabher, F
Alves, TC
Jurczak, MJ
Jornayvaz, FR
Zhang, DY
Hsiao, JJ
Martin-Montalvo, A
Fischer-Rosinsky, A
Spranger, J
Pfeiffer, AF
Jordan, J
Fromm, MF
Konig, J
Lieske, S
Carmean, CM
Frederick, DW
Weismann, D
Knauf, F
Irusta, PM
De Cabo, R
Helfand, SL
Samuel, VT
Shulman, GI
AF Birkenfeld, Andreas L.
Lee, Hui-Young
Guebre-Egziabher, Fitsum
Alves, Tiago C.
Jurczak, Michael J.
Jornayvaz, Francois R.
Zhang, Dongyang
Hsiao, Jennifer J.
Martin-Montalvo, Alejandro
Fischer-Rosinsky, Antje
Spranger, Joachim
Pfeiffer, Andreas F.
Jordan, Jens
Fromm, Martin F.
Koenig, Joerg
Lieske, Stefanie
Carmean, Christopher M.
Frederick, David W.
Weismann, Dirk
Knauf, Felix
Irusta, Pablo M.
De Cabo, Rafael
Helfand, Stephen L.
Samuel, Varman T.
Shulman, Gerald I.
TI Deletion of the Mammalian INDY Homo log Mimics Aspects of Dietary
Restriction and Protects against Adiposity and Insulin Resistance in
Mice
SO CELL METABOLISM
LA English
DT Article
ID COUPLED CITRATE TRANSPORTER; EXTENDING GENE INDY; FATTY LIVER-DISEASE;
LIFE-SPAN; CALORIE RESTRICTION; MITOCHONDRIAL BIOGENESIS;
CAENORHABDITIS-ELEGANS; INDUCED OBESITY; GLUCOSE-HOMEOSTASIS; CHRONIC
ACTIVATION
AB Reduced expression of the Indy (I'm Not Dead, Yet) gene in D. melanogaster and its homolog in C. elegans prolongs life span and in D. melanogaster augments mitochondrial biogenesis in a manner akin to caloric restriction. However, the cellular mechanism by which Indy does this is unknown. Here, we report on the knockout mouse model of the mammalian Indy (mIndy) homolog, SLC13A5. Deletion of mlndy in mice (mINDY(-/-) mice) reduces hepatocellular ATP/ADP ratio, activates hepatic AMPK, induces PGC-1 alpha, inhibits ACC-2, and reduces SREBP-1c levels. This signaling network promotes hepatic mitochondrial biogenesis, lipid oxidation, and energy expenditure and attenuates hepatic de novo lipogenesis. Together, these traits protect mINDY(-/-) mice from the adiposity and insulin resistance that evolve with high-fat feeding and aging. Our studies demonstrate a profound effect of mlndy on mammalian energy metabolism and suggest that mINDY might be a therapeutic target for the treatment of obesity and type 2 diabetes.
C1 [Birkenfeld, Andreas L.; Lee, Hui-Young; Guebre-Egziabher, Fitsum; Alves, Tiago C.; Jurczak, Michael J.; Jornayvaz, Francois R.; Zhang, Dongyang; Hsiao, Jennifer J.; Carmean, Christopher M.; Frederick, David W.; Weismann, Dirk; Knauf, Felix; Samuel, Varman T.; Shulman, Gerald I.] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06520 USA.
[Birkenfeld, Andreas L.; Lee, Hui-Young; Guebre-Egziabher, Fitsum; Alves, Tiago C.; Jurczak, Michael J.; Jornayvaz, Francois R.; Zhang, Dongyang; Hsiao, Jennifer J.; Carmean, Christopher M.; Frederick, David W.; Weismann, Dirk; Knauf, Felix; Samuel, Varman T.; Shulman, Gerald I.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA.
[Birkenfeld, Andreas L.; Lee, Hui-Young; Guebre-Egziabher, Fitsum; Alves, Tiago C.; Jurczak, Michael J.; Jornayvaz, Francois R.; Zhang, Dongyang; Hsiao, Jennifer J.; Carmean, Christopher M.; Frederick, David W.; Weismann, Dirk; Knauf, Felix; Samuel, Varman T.; Shulman, Gerald I.] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06520 USA.
[Birkenfeld, Andreas L.; Spranger, Joachim; Pfeiffer, Andreas F.; Lieske, Stefanie] German Inst Human Nutr Potsdam Rehbrucke, D-14558 Nuthetal, Germany.
[Birkenfeld, Andreas L.; Fischer-Rosinsky, Antje; Spranger, Joachim; Pfeiffer, Andreas F.] Charite Univ Sch Med, D-10117 Berlin, Germany.
[Martin-Montalvo, Alejandro; De Cabo, Rafael] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA.
[Jordan, Jens] Hannover Med Sch, Inst Clin Pharmacol, D-30625 Hannover, Germany.
[Fromm, Martin F.; Koenig, Joerg] Univ Erlangen Nurnberg, Inst Expt & Clin Pharmacol & Toxicol, D-91023 Erlangen, Germany.
[Irusta, Pablo M.] Georgetown Univ, Dept Human Sci, Washington, DC 20057 USA.
[Helfand, Stephen L.] Brown Univ, Dept Mol Biol Cell Biol & Biochem, Providence, RI 02912 USA.
RP Shulman, GI (reprint author), Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06520 USA.
EM gerald.shulman@yale.edu
RI de Cabo, Rafael/J-5230-2016; Martin-Montalvo, Alejandro/C-2031-2017;
OI de Cabo, Rafael/0000-0002-3354-2442; Martin-Montalvo,
Alejandro/0000-0002-3886-5355; Jurczak, Michael/0000-0002-6335-6915; ,
rafael/0000-0003-2830-5693
FU United States Public Health Service [R01 DK-40936, U24 DK-59635, P30
DK-45735, P30 DK-034989, R37 AG-16667]; National Institute of Aging;
American Diabetes Association; German Research Association (Deutsche
Forschungsgemeinschaft) [Bi1292/2-1]; German Diabetes Association
(Deutsche Diabetes Gesellschaft)
FX We thank Xiaoxian Ma, Mario Kahn, Bias Guigni, Yanna Kosover, and Debbie
C. Jiang for their excellent technical support in these studies; the
UCHC transgenic facility for making the mice; and Lothar Willmitzer,
Max-Planck Institute of Molecular Plant Physiology Potsdam, for help
with plasma metabolite measurements. This work was in part supported by
the United States Public Health Service, grants R01 DK-40936 (G.I.S.),
U24 DK-59635 (V.T.S. and G.I.S.), P30 DK-45735, P30 DK-034989, and R37
AG-16667 (S.L.H.); and the intramural research program of the National
Institute of Aging and a Mentor-Based Postdoctoral Fellowship Award from
the American Diabetes Association (G.I.S.). A.L.B. was supported by DFG
grant Bi1292/2-1 from the German Research Association (Deutsche
Forschungsgemeinschaft) and a project grant from the German Diabetes
Association (Deutsche Diabetes Gesellschaft).
NR 60
TC 63
Z9 65
U1 1
U2 10
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
EI 1932-7420
J9 CELL METAB
JI Cell Metab.
PD AUG 3
PY 2011
VL 14
IS 2
BP 184
EP 195
DI 10.1016/j.cmet.2011.06.009
PG 12
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 803UE
UT WOS:000293606300009
PM 21803289
ER
PT J
AU Kouokam, JC
Huskens, D
Schols, D
Johannemann, A
Riedell, SK
Walter, W
Walker, JM
Matoba, N
O'Keefe, BR
Palmer, KE
AF Kouokam, Joseph Calvin
Huskens, Dana
Schols, Dominique
Johannemann, Andrew
Riedell, Shonna K.
Walter, Wendye
Walker, Janice M.
Matoba, Nobuyuki
O'Keefe, Barry R.
Palmer, Kenneth E.
TI Investigation of Griffithsin's Interactions with Human Cells Confirms
Its Outstanding Safety and Efficacy Profile as a Microbicide Candidate
SO PLOS ONE
LA English
DT Article
ID ANTI-HIV ACTIVITY; ANTIVIRAL PROTEIN GRIFFITHSIN; ENTRY INHIBITOR
GRIFFITHSIN; FALSE DISCOVERY RATE; CYANOVIRIN-N; INACTIVATING PROTEIN;
CARBOHYDRATE-BINDING; GENE-EXPRESSION; VIRUS-INFECTIONS; NONOXYNOL-9
AB Many natural product-derived lectins such as the red algal lectin griffithsin (GRFT) have potent in vitro activity against viruses that display dense clusters of oligomannose N-linked glycans (NLG) on their surface envelope glycoproteins. However, since oligomannose NLG are also found on some host proteins it is possible that treatment with antiviral lectins may trigger undesirable side effects. For other antiviral lectins such as concanavalin A, banana lectin and cyanovirin-N (CV-N), interactions between the lectin and as yet undescribed cellular moieties have been reported to induce undesirable side effects including secretion of inflammatory cytokines and activation of host T-cells. We show that GRFT, unlike CV-N, binds the surface of human epithelial and peripheral blood mononuclear cells (PBMC) through an exclusively oligosaccharide-dependent interaction. In contrast to several other antiviral lectins however, GRFT treatment induces only minimal changes in secretion of inflammatory cytokines and chemokines by epithelial cells or human PBMC, has no measureable effect on cell viability and does not significantly upregulate markers of T-cell activation. In addition, GRFT appears to retain antiviral activity once bound to the surface of PBMC. Finally, RNA microarray studies show that, while CV-N and ConA regulate expression of a multitude of cellular genes, GRFT treatment effects only minimal alterations in the gene expression profile of a human ectocervical cell line. These studies indicate that GRFT has an outstanding safety profile with little evidence of induced toxicity, T-cell activation or deleterious immunological consequence, unique attributes for a natural product-derived lectin.
C1 [Kouokam, Joseph Calvin; Johannemann, Andrew; Riedell, Shonna K.; Walter, Wendye; Walker, Janice M.; Matoba, Nobuyuki; Palmer, Kenneth E.] Univ Louisville, Sch Med, Owensboro Canc Res Program, James Graham Brown Canc Ctr, Louisville, KY 40292 USA.
[Kouokam, Joseph Calvin; Johannemann, Andrew; Riedell, Shonna K.; Walter, Wendye; Walker, Janice M.; Matoba, Nobuyuki; Palmer, Kenneth E.] Univ Louisville, Sch Med, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA.
[Huskens, Dana; Schols, Dominique] Katholieke Univ Leuven, Rega Inst Med Res, Louvain, Belgium.
[O'Keefe, Barry R.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21701 USA.
RP Kouokam, JC (reprint author), Univ Louisville, Sch Med, Owensboro Canc Res Program, James Graham Brown Canc Ctr, Louisville, KY 40292 USA.
EM kepalm02@louisville.edu
OI Palmer, Kenneth/0000-0002-2811-1111
FU National Institutes of Health [AI076169]; National Center for Research
Resources [INBRE-P20 RR016481, COBRE-P20RR018733]; James Graham Brown
Foundation; K. U. Leuven; GOA [10/014, 10/018, G.485.08]; CHAARM;
Dormeur Investment Service Ltd.
FX This work was supported by National Institutes of Health grant AI076169
to KEP. Part of this work was performed with the assistance of the
University of Louisville Brown Cancer Center Microarray Facility, which
is supported by the National Center for Research Resources IDeA Awards
INBRE-P20 RR016481 and COBRE-P20RR018733, the James Graham Brown
Foundation, and user fees. DH was supported by a PDM from the K. U.
Leuven. The work at the K. U. Leuven was supported by the GOA no.
10/014, PF no. 10/018, FWO no. G.485.08, the CHAARM project, and the
Dormeur Investment Service Ltd. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 48
TC 45
Z9 46
U1 1
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 2
PY 2011
VL 6
IS 8
AR e22635
DI 10.1371/journal.pone.0022635
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 802LF
UT WOS:000293511900010
PM 21829638
ER
PT J
AU Cole, HA
Howard, BH
Clark, DJ
AF Cole, Hope A.
Howard, Bruce H.
Clark, David J.
TI The centromeric nucleosome of budding yeast is perfectly positioned and
covers the entire centromere
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE chromatin; histone; Saccharomyces cerevisiae
ID SACCHAROMYCES-CEREVISIAE; CENP-A; DNA; PROTEIN; TRANSCRIPTION; CORE;
COMPONENT; HISTONES; COMPLEX; BINDING
AB The centromeres of budding yeast are similar to 120 bp in size and contain three functional elements: an AT-rich region flanked by binding sites for Cbf1 and CBF3. A specialized nucleosome containing the H3 variant Cse4 (CenH3) is formed at the centromere. Our genome-wide paired-end sequencing of nucleosomal DNA reveals that the centromeric nucleosome contains a micrococcal nuclease-resistant kernel of 123-135 bp, depending on the centromere, and is therefore significantly shorter than the canonical nucleosome. Unlike canonical nucleosomes, the centromeric nucleosome is essentially perfectly positioned. The entire centromere is included, together with at least 1 bp of DNA upstream of the Cbf1 site and at least 4 bp downstream of the CBF3 site. The fact that the binding sites for Cbf1 and CBF3 are included within the centromeric nucleosome has important implications for models of the centromeric nucleosome and for kinetochore function.
C1 [Cole, Hope A.; Howard, Bruce H.; Clark, David J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
RP Clark, DJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
EM clarkda@mail.nih.gov
FU National Institutes of Health (NIH), National Institute of Child Health
and Human Development
FX We thank Munira Basrai, Steve Henikoff, and Carl Wu for helpful comments
on the manuscript. We thank Kip Bodi and Michael Berne at the Tufts
University Core Facility for paired-end sequencing. This work was
supported by the Intramural Research Program of the National Institutes
of Health (NIH), National Institute of Child Health and Human
Development.
NR 37
TC 39
Z9 39
U1 1
U2 3
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD AUG 2
PY 2011
VL 108
IS 31
BP 12687
EP 12692
DI 10.1073/pnas.1104978108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 800SC
UT WOS:000293385700035
PM 21768332
ER
PT J
AU Chamero, P
Katsoulidou, V
Hendrix, P
Bufe, B
Roberts, R
Matsunami, H
Abramowitz, J
Birnbaumer, L
Zufall, F
Leinders-Zufall, T
AF Chamero, Pablo
Katsoulidou, Vicky
Hendrix, Philipp
Bufe, Bernd
Roberts, Richard
Matsunami, Hiroaki
Abramowitz, Joel
Birnbaumer, Lutz
Zufall, Frank
Leinders-Zufall, Trese
TI G protein G alpha o is essential for vomeronasal function and aggressive
behavior in mice
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID PUTATIVE PHEROMONE RECEPTORS; ACCESSORY OLFACTORY-BULB; SENSORY NEURONS;
MUTANT MICE; DIFFERENTIAL EXPRESSION; MULTIGENE FAMILY; PHOSPHOLIPASE-C;
CATION CHANNEL; MESSENGER-RNAS; BETA-GAMMA
AB The rodent vomeronasal organ (VNO) mediates the regulation of species-specific and interspecies social behaviors. We have used gene targeting to examine the role of the G protein G alpha o, encoded by the gene Gnao1, in vomeronasal function. We used the Cre-loxP system to delete G alpha o in those cells that express olfactory marker protein, which includes all vomeronasal sensory neurons of the basal layer of the VNO sensory epithelium. Using electrophysiology and calcium imaging, we show that the conditional null mice exhibit strikingly reduced sensory responses in V2R receptor-expressing vomeronasal sensory neurons to specific molecular cues, including MHC1 antigens, major urinary proteins, and exocrine gland-secreting peptide. G alpha o is also vital for vomeronasal sensing of two N-formylated mitochondrially encoded peptides derived from NADH dehydrogenase 1. Furthermore, we show that G alpha o is an essential requirement for the display of male-male territorial aggression as well as maternal aggression in mice. Finally, we show that G alpha o-dependent maternal aggression can be induced by major urinary proteins. These cellular and behavioral phenotypes identify G alpha o as the primary G-protein alpha-subunit mediating the detection of peptide and protein pheromones by sensory neurons of the VNO.
C1 [Abramowitz, Joel; Birnbaumer, Lutz] NIH, Neurobiol Lab, Div Intramural Res, Res Triangle Pk, NC 27709 USA.
[Chamero, Pablo; Katsoulidou, Vicky; Hendrix, Philipp; Bufe, Bernd; Zufall, Frank; Leinders-Zufall, Trese] Univ Saarland, Sch Med, Dept Physiol, D-66424 Homburg, Germany.
[Roberts, Richard; Matsunami, Hiroaki] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA.
[Roberts, Richard; Matsunami, Hiroaki] Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA.
RP Birnbaumer, L (reprint author), NIH, Neurobiol Lab, Div Intramural Res, Res Triangle Pk, NC 27709 USA.
EM birnbau1@niehs.nih.gov; frank.zufall@uks.eu; trese.leinders@uks.eu
RI Leinders-Zufall, Trese/B-4103-2009; Abramowitz, Joel/A-2620-2015;
OI Leinders-Zufall, Trese/0000-0002-0678-362X; Chamero,
Pablo/0000-0002-4305-1073
FU Deutsche Forschungsgemeinschaft [CH 920/2-1, SFB 530, SFB 894]; National
Institutes of Health [Z01 ES-101643, DC010857]; Volkswagen Foundation
FX We thank P. Mombaerts for supplying OMP-Cre mice, K. Touhara for the
ESP1 plasmid, R. Tirindelli for the V2R2 antibody, and M. Pyrski and T.
Meier for help with genotyping. This work was supported by Deutsche
Forschungsgemeinschaft Grants CH 920/2-1 (to P. C.), SFB 530 (to F.Z.),
SFB 894 (to F.Z.), and SFB 894 (to T.L.-Z.), Intramural Research Program
of the National Institutes of Health Project Z01 ES-101643 (to L. B.),
National Institutes of Health Grant DC010857 (to H. M.), and the
Volkswagen Foundation (to T.L.-Z.). Also, T.L.-Z. is a Lichtenberg
Professor of the Volkswagen Foundation.
NR 52
TC 65
Z9 66
U1 3
U2 15
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD AUG 2
PY 2011
VL 108
IS 31
BP 12898
EP 12903
DI 10.1073/pnas.1107770108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 800SC
UT WOS:000293385700071
PM 21768373
ER
PT J
AU Ieva, R
Tian, P
Peterson, JH
Bernstein, HD
AF Ieva, Raffaele
Tian, Pu
Peterson, Janine H.
Bernstein, Harris D.
TI Sequential and spatially restricted interactions of assembly factors
with an autotransporter beta domain
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE membrane protein assembly; molecular chaperones; protein translocation
ID OUTER-MEMBRANE PROTEINS; ESCHERICHIA-COLI; BACTERIAL AUTOTRANSPORTER;
CRYSTAL-STRUCTURE; YAET COMPLEX; SECRETION; BAMA; CHAPERONE; SKP;
COMPONENT
AB Autotransporters are bacterial virulence factors that consist of an N-terminal extracellular ("passenger") domain and a C-terminal beta barrel domain ("beta domain") that resides in the outer membrane. Here we used an in vivo site-specific photocrosslinking approach to gain insight into the mechanism by which the beta domain is integrated into the outer membrane and the relationship between beta domain assembly and passenger domain secretion. We found that periplasmic chaperones and specific components of the beta barrel assembly machinery (Bam) complex interact with the beta domain of the Escherichia coli O157:H7 autotransporter extracellular serine protease P (EspP) in a temporally and spatially regulated fashion. Although the chaperone Skp initially interacted with the entire beta domain, BamA, BamB, and BamD subsequently interacted with discrete beta domain regions. BamB and BamD remained bound to the beta domain longer than BamA and therefore appeared to function at a later stage of assembly. Interestingly, we obtained evidence that the completion of beta domain assembly is regulated by an intrinsic checkpoint mechanism that requires the completion of passenger domain secretion. In addition to leading to a detailed model of autotransporter biogenesis, our results suggest that the lipoprotein components of the Bam complex play a direct role in the membrane integration of beta barrel proteins.
C1 [Ieva, Raffaele; Tian, Pu; Peterson, Janine H.; Bernstein, Harris D.] NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA.
RP Bernstein, HD (reprint author), NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA.
EM harris_bernstein@nih.gov
RI TIAN, PU/F-5739-2012; Ieva, Raffaele/J-9207-2014
OI Ieva, Raffaele/0000-0002-3405-0650
FU National Institute of Diabetes and Digestive and Kidney Diseases
FX We thank Susan Buchanan, Jim Fairman, and Olga Pavlova for critical
reading of the manuscript. We thank Travis Barnard for providing
illustrations of the crystal structure of the EspP beta domain and the
National Institutes of Health Division of Medical Arts for helping to
construct Fig. 5. This work was supported by the Intramural Research
Program of the National Institute of Diabetes and Digestive and Kidney
Diseases.
NR 43
TC 57
Z9 58
U1 0
U2 9
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD AUG 2
PY 2011
VL 108
IS 31
BP E383
EP E391
DI 10.1073/pnas.1103827108
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 800SC
UT WOS:000293385700011
PM 21646511
ER
PT J
AU Li, J
Pattaradilokrat, S
Zhu, F
Jiang, HY
Liu, SF
Hong, LX
Fu, Y
Koo, L
Xu, WY
Pan, WQ
Carlton, JM
Kaneko, O
Carter, R
Wootton, JC
Su, XZ
AF Li, Jian
Pattaradilokrat, Sittiporn
Zhu, Feng
Jiang, Hongying
Liu, Shengfa
Hong, Lingxian
Fu, Yong
Koo, Lily
Xu, Wenyue
Pan, Weiqing
Carlton, Jane M.
Kaneko, Osamu
Carter, Richard
Wootton, John C.
Su, Xin-zhuan
TI Linkage maps from multiple genetic crosses and loci linked to
growth-related virulent phenotype in Plasmodium yoelii
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE genetic mapping; inheritance; crossover; rodent
ID RODENT MALARIA PARASITE; RECOMBINATION PARAMETERS; MUTUAL INFORMATION;
GROUP SELECTION; FALCIPARUM; PROTEIN; RESISTANCE; REVEALS; TARGETS;
GENOME
AB Plasmodium yoelii is an excellent model for studying malaria pathogenesis that is often intractable to investigate using human parasites; however, genetic studies of the parasite have been hindered by lack of genome-wide linkage resources. Here, we performed 14 genetic crosses between three pairs of P. yoelii clones/subspecies, isolated 75 independent recombinant progeny from the crosses, and constructed a high-resolution linkage map for this parasite. Microsatellite genotypes from the progeny formed 14 linkage groups belonging to the 14 parasite chromosomes, allowing assignment of sequence contigs to chromosomes. Growth-related virulent phenotypes from 25 progeny of one of the crosses were significantly associated with a major locus on chromosome 13 and with two secondary loci on chromosomes 7 and 10. The chromosome 10 and 13 loci are both linked to day 5 parasitemia, and their effects on parasite growth rate are independent but additive. The locus on chromosome 7 is associated with day 10 parasitemia. The chromosome 13 locus spans similar to 220 kb of DNA containing 51 predicted genes, including the P. yoelii erythrocyte binding ligand, in which a C741Y substitution in the R6 domain is implicated in the change of growth rate. Similarly, the chromosome 10 locus spans similar to 234 kb with 71 candidate genes, containing a member of the 235-kDa rhoptry proteins (Py235) that can bind to the erythrocyte surface membrane. Atypical virulent phenotypes among the progeny were also observed. This study provides critical tools and information for genetic investigations of virulence and biology of P. yoelii.
C1 [Li, Jian; Pattaradilokrat, Sittiporn; Jiang, Hongying; Su, Xin-zhuan] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
[Koo, Lily] NIAID, Res Technol Branch, NIH, Bethesda, MD 20892 USA.
[Fu, Yong; Xu, Wenyue] Third Mil Med Univ, Dept Pathogen Biol, Chongqing 400038, Peoples R China.
[Li, Jian; Zhu, Feng; Liu, Shengfa; Hong, Lingxian] Xiamen Univ, Sch Life Sci, State Key Lab Stress Cell Biol, Xiamen 361005, Fujian, Peoples R China.
[Pan, Weiqing] Second Mil Med Univ, Dept Pathogen Biol, Shanghai 200433, Peoples R China.
[Carlton, Jane M.] NYU, Langone Med Ctr, Dept Med Parasitol, New York, NY 10010 USA.
[Kaneko, Osamu] Nagasaki Univ, Global Ctr Excellence Program, Nagasaki 8528523, Japan.
[Kaneko, Osamu] Nagasaki Univ, Dept Protozool, Inst Trop Med, Nagasaki 8528523, Japan.
[Carter, Richard] Univ Edinburgh, Ashworth Labs, Inst Cell Anim & Populat Biol, Div Biol Sci, Edinburgh EH9 3JT, Midlothian, Scotland.
[Wootton, John C.] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Su, XZ (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM xsu@niaid.nih.gov
OI Su, Xinzhuan/0000-0003-3246-3248
FU National Basic Research Program of China, 973 Program [2007CB513103];
Science Planning Program of Fujian Province [2010J1008]; 111 Project of
Education of China [B06016]; Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health; National Center for Biotechnology Information, National Library
of Medicine, National Institutes of Health
FX We thank Drs. Karl W. Broman and Na Li for advice on QTL analysis and
National Institute of Allergy and Infectious Diseases intramural editor
Brenda Rae Marshall for assistance. This work was supported by grants
from the National Basic Research Program of China, 973 Program (Grant
2007CB513103), the Science Planning Program of Fujian Province (Grant
2010J1008), and the 111 Project of Education of China (Grant B06016) as
well as by the Intramural Research Program of the Division of Intramural
Research, National Institute of Allergy and Infectious Diseases,
National Institutes of Health. J.C.W. was supported by the Intramural
Program of the National Center for Biotechnology Information, National
Library of Medicine, National Institutes of Health.
NR 41
TC 19
Z9 19
U1 0
U2 3
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD AUG 2
PY 2011
VL 108
IS 31
BP E374
EP E382
DI 10.1073/pnas.1102261108
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 800SC
UT WOS:000293385700010
PM 21690382
ER
PT J
AU Allen, JA
Yadav, PN
Setola, V
Farrell, M
Roth, BL
AF Allen, J. A.
Yadav, P. N.
Setola, V.
Farrell, M.
Roth, B. L.
TI Schizophrenia risk gene CAV1 is both pro-psychotic and required for
atypical antipsychotic drug actions in vivo
SO TRANSLATIONAL PSYCHIATRY
LA English
DT Article
DE antipsychotic; caveolin; clozapine; 5-HT2A; schizophrenia
ID SEROTONIN RECEPTORS; PREPULSE INHIBITION; COMMON VARIANTS; DEFICITS;
MICRODOMAINS; TRAFFICKING; PROTEINS; NEURONS; PSD-95; MODEL
AB Caveolin-1 (Cav-1) is a scaffolding protein important for regulating receptor signaling cascades by partitioning signaling molecules into membrane microdomains. Disruption of the CAV1 gene has recently been identified as a rare structural variant associated with schizophrenia. Although Cav-1 knockout (KO) mice displayed no baseline behavioral disruptions, Cav-1 KO mice, similar to schizophrenic individuals, exhibited increased sensitivity to the psychotomimetic N-methyl-D-aspartate receptor antagonist phencyclidine (PCP). Thus, PCP disruption of prepulse inhibition (PPI) and PCP-induced mouse locomotor activity were both enhanced by genetic deletion of Cav-1. Interestingly, genetic deletion of Cav-1 rendered the atypical antipsychotics clozapine and olanzapine and the 5-HT2A-selective antagonist M100907 ineffective at normalizing PCP-induced disruption of PPI. We also discovered that genetic deletion of Cav-1 attenuated 5-HT2A-induced c-Fos and egr-1 expression in mouse frontal cortex and also reduced 5-HT2A-mediated Ca2+ mobilization in primary cortical neuronal cultures. The behavioral effects of the 5-HT2A agonist (2,5-dimethoxy-4-iodoamphetamine) including head twitch responses and disruption of PPI were also attenuated by genetic deletion of Cav-1, indicating that Cav-1 is required for both inverse agonist (that is, atypical antipsychotic drug) and agonist actions at 5-HT2A receptors. This study demonstrates that disruption of the CAV1 gene-a rare structural variant associated with schizophrenia-is not only pro-psychotic but also attenuates atypical antipsychotic drug actions. Translational Psychiatry (2011) 1, e33; doi:10.1038/tp.2011.35; published online 16 August 2011
C1 [Allen, J. A.; Yadav, P. N.; Setola, V.; Farrell, M.; Roth, B. L.] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA.
[Allen, J. A.; Yadav, P. N.; Setola, V.; Farrell, M.; Roth, B. L.] Univ N Carolina, Sch Pharm, Dept Pharmacol, Chapel Hill, NC 27599 USA.
[Setola, V.; Roth, B. L.] Univ N Carolina, Sch Med, NIMH, Psychoact Drug Screening Program, Chapel Hill, NC 27599 USA.
[Setola, V.; Roth, B. L.] Univ N Carolina, Sch Pharm, NIMH, Psychoact Drug Screening Program, Chapel Hill, NC 27599 USA.
[Roth, B. L.] Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC 27599 USA.
[Roth, B. L.] Univ N Carolina, Sch Pharm, Dept Psychiat, Chapel Hill, NC 27599 USA.
[Roth, B. L.] Univ N Carolina, Sch Med, Dept Med Chem & Nat Prod, Chapel Hill, NC 27599 USA.
[Roth, B. L.] Univ N Carolina, Sch Pharm, Dept Med Chem & Nat Prod, Chapel Hill, NC 27599 USA.
RP Roth, BL (reprint author), Univ N Carolina, Sch Med, Dept Pharmacol, 4007 Genet Med Bldg, Chapel Hill, NC 27599 USA.
EM bryan_roth@med.unc.edu
RI Roth, Bryan/F-3928-2010; Allen, John/D-6141-2011
FU National Institutes of Health [PHS RO1MH61887, U19MH82441, RO1DA017204,
HHSN-271-2008-00025-C]; NIH National Research Service Award
[F31MH091921-01, T32HD040127-07]; UNC-Carolina Institute for
Developmental Disabilities
FX This work was supported by research grants from the National Institutes
of Health, PHS RO1MH61887, U19MH82441, RO1DA017204 and
HHSN-271-2008-00025-C to BLR MF was supported by an NIH National
Research Service Award F31MH091921-01. JAA was supported by NIH National
Research Service Award training grant T32HD040127-07 and the
UNC-Carolina Institute for Developmental Disabilities.
NR 36
TC 8
Z9 8
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2158-3188
J9 TRANSL PSYCHIAT
JI Transl. Psychiatr.
PD AUG
PY 2011
VL 1
AR e33
DI 10.1038/tp.2011.35
PG 9
WC Psychiatry
SC Psychiatry
GA 971PF
UT WOS:000306215600006
PM 22832607
ER
PT J
AU Newburn, EN
Hyde, TM
Ye, T
Morita, Y
Weinberger, DR
Kleinman, JE
Lipska, BK
AF Newburn, E. N.
Hyde, T. M.
Ye, T.
Morita, Y.
Weinberger, D. R.
Kleinman, J. E.
Lipska, B. K.
TI Interactions of human truncated DISC1 proteins: implications for
schizophrenia
SO TRANSLATIONAL PSYCHIATRY
LA English
DT Article
DE DISC1; FEZ1; GSK3-B; NDEL1; PDE4B; schizophrenia
ID NEURITE OUTGROWTH; BEHAVIORAL PHENOTYPES; GENE-EXPRESSION;
DISRUPTED-IN-SCHIZOPHRENIA-1; CORTEX; NUDEL; MICE; POLYMORPHISMS;
MUTATION; BINDING
AB Numerous genetic linkage and association reports have implicated the Disrupted-in-Schizophrenia (DISC1) gene in psychiatric illness. The Scottish family translocation, predicted to encode a C-terminus-truncated protein, suggests involvement of short isoforms in the pathophysiology of mental disorders. We recently reported complex alternative splicing patterns for the DISC1 gene and found that short isoforms are overexpressed in the brains of patients with schizophrenia and in carriers of risk-associated alleles. Investigation into the protein-protein interactions of alternative DISC1 isoforms may provide information about the functional consequences of overexpression of truncated forms in mental illness. Human embryonic kidney (HEK293) cells were transiently co-transfected with human epitope-tagged DISC1 variants and epitope-tagged NDEL1, FEZ1, GSK3 beta and PDE4B constructs. Co-immunoprecipitation assays demonstrated that all truncated DISC1 variants formed complexes with full-length DISC1. Short DISC1 splice variants L Delta 78, L Delta 3 and Esv1 showed reduced or no binding to NDEL1 and PDE4B proteins, but fully interacted with FEZ1 and GSK3 beta. The temporal expression pattern of GSK3b in the human postmortem tissue across the lifespan closely resembled that of the truncated DISC1 variants, suggesting the possibility of interactions between these proteins in the human brain. Our results suggest that complexes of full-length DISC1 with truncated DISC1 variants may result in cellular disturbances critical to DISC1 function. Translational Psychiatry (2011) 1, e30; doi:10.1038/tp.2011.31; published online 16 August 2011
C1 [Newburn, E. N.; Hyde, T. M.; Ye, T.; Morita, Y.; Weinberger, D. R.; Kleinman, J. E.; Lipska, B. K.] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
RP Lipska, BK (reprint author), NIMH, Clin Brain Disorders Branch, NIH, 10 Ctr Dr,Bldg 10,Room 4N312, Bethesda, MD 20892 USA.
EM lipskab@mail.nih.gov
NR 23
TC 5
Z9 5
U1 1
U2 13
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2158-3188
J9 TRANSL PSYCHIAT
JI Transl. Psychiatr.
PD AUG
PY 2011
VL 1
AR e30
DI 10.1038/tp.2011.31
PG 6
WC Psychiatry
SC Psychiatry
GA 971PF
UT WOS:000306215600003
PM 22832604
ER
PT J
AU Rao, JS
Rapoport, SI
Kim, HW
AF Rao, J. S.
Rapoport, S. I.
Kim, H-W
TI Altered neuroinflammatory, arachidonic acid cascade and synaptic markers
in postmortem Alzheimer's disease brain
SO TRANSLATIONAL PSYCHIATRY
LA English
DT Article
DE Alzheimer's disease; arachidonic acid cascade; inflammation;
synaptophysin; drebrin
ID CENTRAL-NERVOUS-SYSTEM; AMYLOID-BETA-PEPTIDES; SMOOTH-MUSCLE-CELLS;
PHOSPHOLIPASE A(2); FRONTAL-CORTEX; DOCOSAHEXAENOIC ACID;
NEURODEGENERATIVE DISEASES; COGNITIVE DEFICITS; PROSTAGLANDIN E-2;
UNANESTHETIZED RATS
AB Alzheimer's disease (AD), a progressive neurodegenerative disorder, is the leading cause of dementia in the elderly. A recent positron emission tomography imaging study demonstrated upregulated brain arachidonic acid (AA) metabolism in AD patients. Further, a mouse model of AD shows an increase in AA-releasing cytosolic phospholipase A(2) (cPLA(2)) in brain, and a reduction in cPLA(2) activity ameliorated cognitive deficits. These observations led us to hypothesize that there is an upregulation of AA cascade and neuroinflammatory markers in the brain of AD patients. To test this hypothesis, we measured protein and mRNA levels of AA cascade, neuroinflammatory and synaptic markers in postmortem frontal cortex from 10 AD patients and 10 age-matched controls. Consistent with our hypothesis, AD frontal cortex showed significant increases in protein and mRNA levels of cPLA(2)-IVA, secretory sPLA(2)-IIA, cyclooxygenase-1 and -2, membrane prostaglandin (PG) synthase-1 and lipoxygenase-12 and -15. Calcium-independent iPLA(2)-VIA and cytosolic PGE(2) synthase were decreased. In addition, interleukin-1 beta, tumor necrosis factor-alpha, glial fibrillary acidic protein and CD11b were increased. AD postmortem brain also showed signs of cellular injury, including decreased synaptophysin and drebrin, pre- and postsynaptic markers. These results indicate that increased AA cascade and inflammatory markers could contribute to AD pathology. Altered brain AA cascade enzymes could be considered therapeutic targets for future drug development. Translational Psychiatry (2011) 1, e31; doi:10.1038/tp.2011.27; published online 16 August 2011
C1 [Rao, J. S.; Rapoport, S. I.; Kim, H-W] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
RP Rao, JS (reprint author), NIA, Brain Physiol & Metab Sect, NIH, 9000 Rockville Pike,Bldg 9,Room 1S-126, Bethesda, MD 20892 USA.
EM HTUjrao@mail.nih.gov
FU PHS [R24MH068855]; Intramural Research Program of the National Institute
on Aging, National Institutes of Health
FX We thank the Harvard Brain Bank, Boston, MA, USA, for providing the
postmortem brain samples under PHS grant number R24MH068855. This
research was entirely supported by the Intramural Research Program of
the National Institute on Aging, National Institutes of Health. We also
thank Dr Eugene Streicher and the Fellows' Editorial Board at the
National Institutes of Health for reviewing the manuscript.
NR 75
TC 21
Z9 23
U1 1
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2158-3188
J9 TRANSL PSYCHIAT
JI Transl. Psychiatr.
PD AUG
PY 2011
VL 1
AR e31
DI 10.1038/tp.2011.27
PG 9
WC Psychiatry
SC Psychiatry
GA 971PF
UT WOS:000306215600004
PM 22832605
ER
PT J
AU Tatarov, I
Panda, A
Petkov, D
Kolappaswamy, K
Thompson, K
Kavirayani, A
Lipsky, MM
Elson, E
Davis, CC
Martin, SS
DeTolla, LJ
AF Tatarov, Ivan
Panda, Aruna
Petkov, Daniel
Kolappaswamy, Krishnan
Thompson, Keyata
Kavirayani, Anoop
Lipsky, Michael M.
Elson, Edward
Davis, Christopher C.
Martin, Stuart S.
DeTolla, Louis J.
TI Effect of Magnetic Fields on Tumor Growth and Viability
SO COMPARATIVE MEDICINE
LA English
DT Article
ID CANCER-CELLS; MICE; INHIBITION; APOPTOSIS; TOXICITY; EXPOSURE; SURVIVAL
AB Breast cancer is the most common nonskin cancer and is the second leading cause of cancer-related deaths in women. Most methods of intervention involve combinations of surgery, chemotherapy, and ionizing radiation. Both chemotherapy and ionizing radiation can be effective against many types of cancer, but they also harm normal tissues. The use of nonionizing, magnetic fields has shown early promise in a number of in vitro and animal studies. Our study tested the effect of varying durations of magnetic exposure on tumor growth and viability in mice injected with breast cancer cells. Cancer cells were labeled through stable expression of firefly luciferase for monitoring of tumor growth and progression by using an in vivo imaging system. We hypothesized that magnetic field exposure would influence tumor growth and progression. Our results showed that exposure of the mice to magnetic fields for 360 min daily for as long as 4 wk suppressed tumor growth. Our study is unique in that it uses an in vivo imaging system to monitor the growth and progression of tumors in real time in individual mice. Our findings support further exploration of the potential of magnetic fields in cancer therapeutics, either as adjunct or primary therapy.
C1 [Tatarov, Ivan; Panda, Aruna; Kolappaswamy, Krishnan; Lipsky, Michael M.; DeTolla, Louis J.] Univ Maryland, Sch Med, Dept Pathol, Comparat Med Program, Baltimore, MD 21201 USA.
[Kolappaswamy, Krishnan; DeTolla, Louis J.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Thompson, Keyata; Martin, Stuart S.] Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA.
[DeTolla, Louis J.] Univ Maryland, Sch Med, Dept Med Infect Dis, Baltimore, MD 21201 USA.
[Thompson, Keyata; Martin, Stuart S.] Univ Maryland, Marlene & Stewart Greenebaum NCI Canc Ctr, Baltimore, MD 21201 USA.
[Elson, Edward; Davis, Christopher C.] Univ Maryland, Dept Elect & Comp Engn, College Pk, MD 20742 USA.
[Kavirayani, Anoop] Jackson Lab, Dept Histopathol & Microscop Sci, Bar Harbor, ME 04609 USA.
[Petkov, Daniel] Univ Calgary, Anim Hlth Unit, Calgary, AB, Canada.
RP Panda, A (reprint author), Univ Maryland, Sch Med, Dept Pathol, Comparat Med Program, Baltimore, MD 21201 USA.
EM apanda@vetmed.umaryland.edu
FU NCI NIH HHS [P30 CA134274]
NR 21
TC 12
Z9 14
U1 4
U2 12
PU AMER ASSOC LABORATORY ANIMAL SCIENCE
PI MEMPHIS
PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA
SN 1532-0820
J9 COMPARATIVE MED
JI Comparative Med.
PD AUG
PY 2011
VL 61
IS 4
BP 339
EP 345
PG 7
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 915QT
UT WOS:000302043200006
PM 22330249
ER
PT J
AU Bossert, JM
Stern, AL
Theberge, FRM
Shaham, Y
AF Bossert, Jennifer M.
Stern, Anna L.
Theberge, Florence R. M.
Shaham, Yavin
TI ROLE FOR VENTRAL MPFC-ACCUMBENS SHELL PROJECTION IN CONTEXT-INDUCED
REINSTATEMENT IN RATS
SO BEHAVIOURAL PHARMACOLOGY
LA English
DT Meeting Abstract
CT 14th Biennial Meeting of the European-Behavioural-Pharmacology-Society
CY AUG 26-29, 2011
CL Amsterdam, NETHERLANDS
SP European Behav Pharmacol Soc
C1 [Bossert, Jennifer M.; Stern, Anna L.; Theberge, Florence R. M.; Shaham, Yavin] NIDA, Behav Neurosci Branch, IRP, NIH,DHHS, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 AUG
PY 2011
VL 22
SU S
BP E53
EP E53
PG 1
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA 893OM
UT WOS:000300365200186
ER
PT J
AU Cifani, C
Di B, MVM
Rice, KC
Ciccocioppo, R
Massi, M
AF Cifani, C.
Di B, M. V. Micioni
Rice, K. C.
Ciccocioppo, R.
Massi, M.
TI EFFECT OF THE SELECTIVE CRF-1 RECEPTOR ANTAGONIST R121919 IN AN ANIMAL
MODEL OF BINGE EATING
SO BEHAVIOURAL PHARMACOLOGY
LA English
DT Meeting Abstract
CT 14th Biennial Meeting of the European-Behavioural-Pharmacology-Society
CY AUG 26-29, 2011
CL Amsterdam, NETHERLANDS
SP European Behav Pharmacol Soc
C1 [Cifani, C.; Di B, M. V. Micioni; 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 2
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 AUG
PY 2011
VL 22
SU S
BP E54
EP E55
PG 2
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA 893OM
UT WOS:000300365200191
ER
PT J
AU Epstein, DH
Preston, KL
AF Epstein, David H.
Preston, Kenzie L.
TI DRUG-DEPENDENT OUTPATIENTS REPORT LOWER STRESS AND MORE HAPPINESS AT
WORK THAN ELSEWHERE
SO BEHAVIOURAL PHARMACOLOGY
LA English
DT Meeting Abstract
CT 14th Biennial Meeting of the European-Behavioural-Pharmacology-Society
CY AUG 26-29, 2011
CL Amsterdam, NETHERLANDS
SP European Behav Pharmacol Soc
C1 [Epstein, David H.; Preston, Kenzie L.] NIDA Intramural Res Program, Treatment Sect, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
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 AUG
PY 2011
VL 22
SU S
BP E23
EP E23
PG 1
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA 893OM
UT WOS:000300365200083
ER
PT J
AU Heilig, M
Hommer, D
George, T
Thorsell, A
Ramchandani, V
Schwandt, M
AF Heilig, Markus
Hommer, Daniel
George, Ted
Thorsell, Annika
Ramchandani, Vijay
Schwandt, Melanie
TI IMAGING BASED BIOMARKERS TO TRANSLATE PRECLINICAL FINDINGS ON THE
PHARMACOLOGY OF ALCOHOLISM
SO BEHAVIOURAL PHARMACOLOGY
LA English
DT Meeting Abstract
CT 14th Biennial Meeting of the European-Behavioural-Pharmacology-Society
CY AUG 26-29, 2011
CL Amsterdam, NETHERLANDS
SP European Behav Pharmacol Soc
C1 [Heilig, Markus; Hommer, Daniel; George, Ted; Thorsell, Annika; Ramchandani, Vijay; Schwandt, Melanie] NIAAA NIH, LCTS, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 AUG
PY 2011
VL 22
SU S
BP E10
EP E10
PG 1
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA 893OM
UT WOS:000300365200038
ER
PT J
AU Holmes, A
Brigman, JL
AF Holmes, A.
Brigman, J. L.
TI PREFRONTAL EMOTIONAL REGULATION AND COGNITIVE FLEXIBILITY FOLLOWING GENE
DELETION OF THE SEROTONIN TRANSPORTER
SO BEHAVIOURAL PHARMACOLOGY
LA English
DT Meeting Abstract
CT 14th Biennial Meeting of the European-Behavioural-Pharmacology-Society
CY AUG 26-29, 2011
CL Amsterdam, NETHERLANDS
SP European Behav Pharmacol Soc
C1 [Holmes, A.; Brigman, J. L.] NIAAA, SBSG, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 AUG
PY 2011
VL 22
SU S
BP E16
EP E16
PG 1
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA 893OM
UT WOS:000300365200058
ER
PT J
AU Norman, N
Hogarth, L
Panlilio, L
Shoaib, M
AF Norman, Nicole
Hogarth, Lee
Panlilio, Leigh
Shoaib, Mohammed
TI ESTABLISHING CONCURRENT CHOICE PROCEDURES WITH INTRAVENOUS NICOTINE AND
SUCROSE IN RATS
SO BEHAVIOURAL PHARMACOLOGY
LA English
DT Meeting Abstract
CT 14th Biennial Meeting of the European-Behavioural-Pharmacology-Society
CY AUG 26-29, 2011
CL Amsterdam, NETHERLANDS
SP European Behav Pharmacol Soc
C1 [Norman, Nicole; Shoaib, Mohammed] Newcastle Univ, Inst Neurosci, Sch Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
[Hogarth, Lee] Univ Nottingham, Sch Psychol, Nottingham NG7 2RD, England.
[Panlilio, Leigh] NIDA, IRP, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 5
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 AUG
PY 2011
VL 22
SU S
BP E51
EP E51
PG 1
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA 893OM
UT WOS:000300365200178
ER
PT J
AU Preston, KL
Epstein, DH
Craig, I
Vahabzadeh, M
Lin, JL
Phillips, KA
AF Preston, Kenzie L.
Epstein, David H.
Craig, Ian
Vahabzadeh, Massoud
Lin, Jia-Ling
Phillips, Karran A.
TI REAL-TIME METHODS TO QUANTIFY EXPOSURE TO PSYCHOSOCIAL STRESS
SO BEHAVIOURAL PHARMACOLOGY
LA English
DT Meeting Abstract
CT 14th Biennial Meeting of the European-Behavioural-Pharmacology-Society
CY AUG 26-29, 2011
CL Amsterdam, NETHERLANDS
SP European Behav Pharmacol Soc
C1 [Preston, Kenzie L.; Epstein, David H.; Craig, Ian; Vahabzadeh, Massoud; Lin, Jia-Ling; Phillips, Karran A.] NIDA, Intramural Res Program, Clin Pharmacol & Therapeut Res Branch, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 AUG
PY 2011
VL 22
SU S
BP E68
EP E68
PG 1
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA 893OM
UT WOS:000300365200238
ER
PT J
AU Shaham, Y
de Wit, H
Epstein, D
Preston, K
AF Shaham, Yavin
de Wit, Harriet
Epstein, David
Preston, Kenzie
TI TRANSLATIONAL RESEARCH BASED ON THE EXTINCTION-REINSTATEMENT MODEL:
RECENT PROGRESS
SO BEHAVIOURAL PHARMACOLOGY
LA English
DT Meeting Abstract
CT 14th Biennial Meeting of the European-Behavioural-Pharmacology-Society
CY AUG 26-29, 2011
CL Amsterdam, NETHERLANDS
SP European Behav Pharmacol Soc
C1 [Shaham, Yavin; Epstein, David; Preston, Kenzie] NIDA, Intramural Res Program, NIH, Baltimore, MD USA.
[de Wit, Harriet] Univ Chicago, Chicago, IL USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
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 AUG
PY 2011
VL 22
SU S
BP E10
EP E10
PG 1
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA 893OM
UT WOS:000300365200037
ER
PT J
AU Pandya, A
AF Pandya, Anand
TI THIS ISSUE: Posttraumatic Stress Disorder: Beyond the DSM-IV
SO PSYCHIATRIC ANNALS
LA English
DT Editorial Material
C1 [Pandya, Anand] Cedars Sinai Med Ctr, Dept Psychiat & Behav Neurosci, Los Angeles, CA USA.
[Pandya, Anand] Univ Calif Los Angeles, Dept Psychiat, Sch Med, Los Angeles, CA 90024 USA.
[Pandya, Anand] Bellevue Hosp, New York, NY USA.
[Pandya, Anand] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA.
[Pandya, Anand] Menninger Clin, Houston, TX USA.
[Pandya, Anand] NIMH, Bethesda, MD USA.
RP Pandya, A (reprint author), 8730 Alden Dr,C-301, Los Angeles, CA 90048 USA.
EM anand.pandya@cshs.org
NR 0
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 AUG
PY 2011
VL 41
IS 8
BP 384
EP 385
DI 10.3928/00485713-20110727-02
PG 2
WC Psychiatry
SC Psychiatry
GA 885HM
UT WOS:000299769600003
ER
PT J
AU Lee, DC
Romero, R
Kim, JS
Tarca, AL
Montenegro, D
Pineles, BL
Kim, E
Lee, J
Kim, SY
Draghici, S
Mittal, P
Kusanovic, JP
Chaiworapongsa, T
Hassan, SS
Kim, CJ
AF Lee, Deug-Chan
Romero, Roberto
Kim, Jung-Sun
Tarca, Adi L.
Montenegro, Daniel
Pineles, Beth L.
Kim, Ernest
Lee, JoonHo
Kim, Sun Young
Draghici, Sorin
Mittal, Pooja
Kusanovic, Juan Pedro
Chaiworapongsa, Tinnakorn
Hassan, Sonia S.
Kim, Chong Jai
TI miR-210 Targets Iron-Sulfur Cluster Scaffold Homologue in Human
Trophoblast Cell Lines Siderosis of Interstitial Trophoblasts as a Novel
Pathology of Preterm Preeclampsia and Small-for-Gestational-Age
Pregnancies
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID PLACENTAL BED; BREAST-CANCER; FETAL-GROWTH; SERUM IRON; SOLUBLE
ENDOGLIN; GESTATIONAL-AGE; GENE-EXPRESSION; SPIRAL ARTERIES; HYPOXIA;
PREGNANCY
AB This study was performed to assess the biological significance of miR-210 in preeclampsia and small-for-gestational-age (SGA) pregnancies. Placental miR-210 expression was evaluated by quantitative RT-PCR (RT-qPCR) in the following groups: i) appropriate-for-gestational-age pregnancies (n = 72), preeclampsia (n = 52), SGA (n = 66), and iv)preeclampsia with SGA (n = 31). The effects of hypoxia (1% O(2)) on miR-210 and iron-sulfur cluster scaffold homologue (ISCU) expressions and miR-210 binding to ISCU 3' UTR were examined in Swan 71 and BeWo cell lines. Perls' reaction (n = 229) and electron microscopy (n = 3) were conducted to verify siderosis of trophoblasts. miR-210 expression was increased in preeclampsia and SGA cases and was decreased with birth weight and gestational age. In both cell lines, miR-210 was induced by hypoxia, whereas ISCU expression was decreased. The luciferase assay confirmed miR-210 binding to ISCU mRNA 3' UTR. RNA interference knockdown of ISCU expression in Swan 71, but not in BeWo, cells resulted in autophagosomal and siderosomal iron accumulation and a fourfold decrease of Matrigel invasion (P = 0.004). Placental ISCU expression was decreased in preeclampsia (P = 0.002) and SGA (P = 0.002) cases. Furthermore, hemosiderin-laden trophoblasts were more frequent in the placental bed of preterm preeclampsia and/or SGA births than in control cases (48.7% versus 17.9%; P = 0.004). Siderosis of interstitial trophoblasts is a novel pathological feature of preeclampsia and SGA. The findings herein suggest that ISCU down-regulation by tniR-210 perturbing trophoblast iron metabolism is associated with defective placentation. (Am J Pathol 2011, 179:590-602; DOI: 10.1016/j.ajpath.2011.04.035)
C1 [Lee, Deug-Chan; Romero, Roberto; Tarca, Adi L.; Montenegro, Daniel; Pineles, Beth L.; Kim, Ernest; Lee, JoonHo; Kim, Sun Young; Mittal, Pooja; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.; Kim, Chong Jai] NICHHD, Dept Hlth & Human Serv, Perinatol Res Branch, NIH, Bethesda, MD 20892 USA.
[Lee, Deug-Chan; Romero, Roberto; Tarca, Adi L.; Montenegro, Daniel; Pineles, Beth L.; Kim, Ernest; Lee, JoonHo; Kim, Sun Young; Mittal, Pooja; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.; Kim, Chong Jai] NICHHD, Dept Hlth & Human Serv, Perinatol Res Branch, NIH, Detroit, MI USA.
[Romero, Roberto; Mittal, Pooja; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Tarca, Adi L.; Draghici, Sorin] Wayne State Univ, Dept Comp Sci, Detroit, MI 48201 USA.
[Kim, Chong Jai] Wayne State Univ, Dept Pathol, Sch Med, Hutzel Womens Hosp, Detroit, MI 48201 USA.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA.
[Kim, Jung-Sun] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pathol, Seoul, South Korea.
RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHHD, NIH,Dept Hlth & Human Serv,Hutzel Womens Hosp, 3990 John R St, Detroit, MI 48201 USA.
EM prbchiefstaff@med.wayne.edu; cjkim@med.wayne.edu
RI Draghici, Sorin/B-3074-2013
OI Draghici, Sorin/0000-0002-0786-8377
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, NIH, Department of Health and Human Services
FX Supported in part by the Perinatology Research Branch, Division of
Intramural Research, Eunice Kennedy Shriver National Institute of Child
Health and Human Development, NIH, Department of Health and Human
Services.
NR 72
TC 39
Z9 46
U1 0
U2 17
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD AUG
PY 2011
VL 179
IS 2
BP 590
EP 602
DI 10.1016/j.ajpath.2011.04.035
PG 13
WC Pathology
SC Pathology
GA 865JM
UT WOS:000298307200006
PM 21801864
ER
PT J
AU Wang, H
Lafdil, F
Wang, L
Park, O
Yin, S
Niu, JY
Miller, AM
Sun, ZL
Gao, B
AF Wang, Hua
Lafdil, Fouad
Wang, Lei
Park, Ogyi
Yin, Shi
Niu, Junyang
Miller, Andrew M.
Sun, Zhaoli
Gao, Bin
TI Hepatoprotective versus Oncogenic Functions of STAT3 in Liver
Tumorigenesis
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID PROMOTES CHEMICAL HEPATOCARCINOGENESIS; HEPATOCELLULAR-CARCINOMA; SIGNAL
TRANSDUCER; TRANSCRIPTION 3; CARBON-TETRACHLORIDE; TARGETED THERAPIES;
OXIDATIVE STRESS; GROWTH-FACTOR; TGF-BETA; CANCER
AB Aberrantly hyperactivated STAT3 has been found in human liver cancers as an oncogene; however, STAT3 has also been shown to exert hepatoprotective effects during liver injury. The balancing act that STAT3 plays between hepatoprotection and liver tumorigenesis remains poorly defined. In this study, the diethylnitrosamine (DEN)-induced liver tumor model and the chronic carbon tetrachloride (CCl(4))-induced liver fibrosis model were both used to investigate the role of STAT3 in liver tumorigenesis. Hepatocyte-specific STAT3 knockout mice were resistant to liver tumorigenesis induced by a single DEN injection, whose tumorigenesis was associated with minimal chronic liver inflammation, injury, and fibrosis. In contrast, long-term CCl(4) treatment resulted in severe hepatic oxidative damage, inflammation,. and fibrosis but rarely induced liver tumor formation in wild-type mice. Despite the oncogenic function of STAT3 in DEN-induced liver tumor, hepatocyte-specific STAT3 knockout mice were more susceptible to liver tumorigenesis after 16 weeks of CCl(4) injection, which was associated with higher levels of liver injury, inflammation, fibrosis, and oxidative DNA damage compared with wild-type mice. These findings suggest that the hepatoprotective feature of STAT3 prevents hepatic damage and fibrosis under the condition of persistent inflammatory stress, consequently suppressing injury-driven liver tumor initiation. Once liver tumor cells have developed, STAT3 likely acts as an oncogenic factor to promote tumor growth. (Am J Pathol 2011, 179:714-724; DOI: 10.1016/j.ajpath.2011.05.005)
C1 [Wang, Hua; Lafdil, Fouad; Wang, Lei; Park, Ogyi; Yin, Shi; Miller, Andrew M.; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA.
[Wang, Hua] Anhui Med Univ, Affiliated Prov Hosp, Dept Oncol, Hefei, Anhui, Peoples R China.
[Niu, Junyang] Anhui Med Univ, Affiliated Prov Hosp, Dept Pathol, Hefei, Anhui, Peoples R China.
[Sun, Zhaoli] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA.
RP Gao, B (reprint author), NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA.
EM bgao@mail.nih.gov
FU National Institute on Alcohol Abuse and Alcoholism, NIH; Natural Science
Foundation of China [30973467/H1611]
FX Supported in part by the intramural program of the National Institute on
Alcohol Abuse and Alcoholism, NIH (B.G.), and in part by the Natural
Science Foundation of China (30973467/H1611 to H.W.).
NR 50
TC 16
Z9 16
U1 0
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD AUG
PY 2011
VL 179
IS 2
BP 714
EP 724
DI 10.1016/j.ajpath.2011.05.005
PG 11
WC Pathology
SC Pathology
GA 865JM
UT WOS:000298307200018
PM 21684247
ER
PT J
AU Butchi, NB
Woods, T
Du, M
Morgan, TW
Peterson, KE
AF Butchi, Niranjan B.
Woods, Tyson
Du, Min
Morgan, Timothy W.
Peterson, Karin E.
TI TLR7 and TLR9 Trigger Distinct Neuroinflammatory Responses in the CNS
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID TOLL-LIKE RECEPTORS; NECROSIS-FACTOR-ALPHA; IMMUNE-RESPONSES;
THERAPEUTIC APPLICATIONS; CEREBROSPINAL-FLUID; VIRUS-INFECTION;
BACTERIAL-DNA; AGONISTS; BRAIN; RECOGNITION
AB Toll-like receptors (TLRs) 7 and 9 recognize nucleic acid determinants from viruses and bacteria and elicit the production of type I interferons and proinflammatory cytokines. TLR7 and TLR9 are similar regarding localization and signal transduction mechanisms. However, stimulation of these receptors has differing effects in modulating viral pathogenesis and in direct toxicity in the central nervous system (CNS). In the present study, we examined the potential of the TLR7 agonist imiquimod and the TLR9 agonist cytosine-phosphate-guanosine oligodeoxynucleotide (CpG-ODN) to induce neuroinflammation after intracerebroventricular inoculation. CpG-ODN induced a more robust inflammatory response than did imiquimod after inoculation into the CNS, with higher levels of several proinflammatory cytokines and chemokines. The increase in cytokines and chemokines correlated with breakdown of the blood-cerebrospinal fluid barrier and recruitment of peripheral cells to the CNS in CpG-ODN-inoculated mice. In contrast, TLR7 agonists induced a strong interferon beta response in the CNS but only low levels of other cytokines. The difference in response to these agonists was not due to differences in distribution or longevity of the agonists but rather was correlated with cytokine production by choroid plexus cells. These results indicate that despite the high similarity of TLR7 and TLR9 in binding nucleic acids and inducing similar downstream signaling, the neuroinflammation response induced by these receptors differs dramatically due, at least in part, to activation of cells in the choroid plexus. (Am J Pathol 2011, 179:783-794; DOI; 10.1016/j.ajpath.2011.04.011)
C1 [Butchi, Niranjan B.; Woods, Tyson; Du, Min; Peterson, Karin E.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Hamilton, MT 59840 USA.
[Morgan, Timothy W.] Louisiana State Univ, Sch Vet Med, Dept Pathobiol Sci, Baton Rouge, LA 70803 USA.
RP Peterson, KE (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA.
EM petersonka@niaid.nih.gov
RI Peterson, Karin/D-1492-2016
OI Peterson, Karin/0000-0003-4177-7249
FU NIH; National Center for Research Resources [IP20RR020159]
FX Supported in part by the Intramural Research Program of the NIH and in
part by National Center for Research Resources grant IP20RR020159.
NR 37
TC 16
Z9 16
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD AUG
PY 2011
VL 179
IS 2
BP 783
EP 794
DI 10.1016/j.ajpath.2011.04.011
PG 12
WC Pathology
SC Pathology
GA 865JM
UT WOS:000298307200025
PM 21801870
ER
PT J
AU Gonzalez, JM
Franzke, CW
Yang, FY
Romero, R
Girardi, G
AF Gonzalez, Juan M.
Franzke, Claus-Werner
Yang, Fengyuan
Romero, Roberto
Girardi, Guillermina
TI Complement Activation Triggers Metalloproteinases Release Inducing
Cervical Remodeling and Preterm Birth in Mice
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID AMNIOTIC-FLUID; MATRIX METALLOPROTEINASES; INTRAAMNIOTIC INFECTION;
HORMONAL-REGULATION; IMMUNE-RESPONSE; C5A RECEPTOR; PROGESTERONE;
EXPRESSION; MOUSE; WOMEN
AB Inflammation is frequently linked to preterm delivery (PTD). Here, we tested the hypothesis that complement activation plays a role in cervical remodeling and PTD. We studied two mouse models of inflammation-induced PTD. The first model was induced by vaginal administration of lipopolysaccharide (LPS) and the second one by administration of progesterone antagonist RU486. Increased cervical C3 deposition and macrophages infiltration and increased serum C3adesArg and C5adesArg levels were observed in both models when compared to gestational age matched controls. A significant increase in collagen degradation, matrix metalloproteinase 9 (MMP-9) activity and tissue distensibility was observed in the cervix in both models. Mice deficient in complement receptor C5a did not show increased MMP-9 activity and cervical remodeling and did not deliver preterm in response to LPS or RU486, suggesting a role for C5aR in the cervical changes that precede PTD. In vitro studies show that macrophages release MMP-9 in response to C5a. Progesterone diminished the amount of C5aR on the macrophages surface, inhibited the release of MMP-9 and prevented PTD. In addition, macrophages depletion also prevented cervical remodeling and PTD in LPS-treated mice. Our studies show that C5a-C5aR interaction is required for MMP-9 release from macrophages, and the cervical remodeling that leads to PTD. Complement inhibition and supplementation with progesterone may be good therapeutic options to prevent this serious pregnancy complication. (Am J Pathol 2011, 179:838-849; DOI: 10.1016/j.ajpath.2011.04.024)
C1 [Gonzalez, Juan M.; Romero, Roberto] NICHHD, Perinatol Res Branch, NIH, Bethesda, MD 20892 USA.
[Franzke, Claus-Werner] Univ Med Ctr Freiburg, Dept Dermatol, Freiburg, Germany.
[Yang, Fengyuan] Wayne State Univ, Dept Chem Engn & Mat Sci & Biomed Engn, Detroit, MI USA.
[Girardi, Guillermina] CUNY, York Coll, Dept Chem Engn & Mat Sci, New York, NY 10021 USA.
RP Girardi, G (reprint author), Queens Med Res Inst, 47 Little France Crescent, Edinburgh EH16 4TY, Midlothian, Scotland.
EM Guillermina.Girardi@ed.ac.uk
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Department of Health and
Human Services
FX Supported by the Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development,
National Institutes of Health, Department of Health and Human Services.
NR 45
TC 61
Z9 64
U1 1
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD AUG
PY 2011
VL 179
IS 2
BP 838
EP 849
DI 10.1016/j.ajpath.2011.04.024
PG 12
WC Pathology
SC Pathology
GA 865JM
UT WOS:000298307200030
PM 21801872
ER
PT J
AU Pett, W
Ryan, JF
Pang, K
Mullikin, JC
Martindale, MQ
Baxevanis, AD
Lavrov, DV
AF Pett, Walker
Ryan, Joseph F.
Pang, Kevin
Mullikin, James C.
Martindale, Mark Q.
Baxevanis, Andreas D.
Lavrov, Dennis V.
TI Extreme mitochondrial evolution in the ctenophore Mnemiopsis leidyi:
Insight from mtDNA and the nuclear genome
SO MITOCHONDRIAL DNA
LA English
DT Article
DE Ctenophora; comparative genomics; cytonuclear coevolution
ID ENCODED TRANSFER-RNAS; RIBOSOMAL-RNA; SECONDARY STRUCTURE;
LEISHMANIA-TARENTOLAE; BILATERIAN ANIMALS; COMPLETE SEQUENCE;
POPULATION-SIZE; BLACK-SEA; DNA; GENES
AB Recent advances in sequencing technology have led to a rapid accumulation of mitochondrial DNA (mtDNA) sequences, which now represent the wide spectrum of animal diversity. However, one animal phylum-Ctenophora-has, to date, remained completely unsampled. Ctenophores, a small group of marine animals, are of interest due to their unusual biology, controversial phylogenetic position, and devastating impact as invasive species. Using data from the Mnemiopsis leidyi genome sequencing project, we Polymerase Chain Reaction (PCR) amplified and analyzed its complete mitochondrial (mt-) genome. At just over 10 kb, the mt-genome of M. leidyi is the smallest animal mtDNA ever reported and is among the most derived. It has lost at least 25 genes, including atp6 and all tRNA genes. We show that atp6 has been relocated to the nuclear genome and has acquired introns and a mitochondrial targeting presequence, while tRNA genes have been genuinely lost, along with nuclear-encoded mt-aminoacyl tRNA synthetases. The mt-genome of M. leidyi also displays extremely high rates of sequence evolution, which likely led to the degeneration of both protein and rRNA genes. In particular, encoded rRNA molecules possess little similarity with their homologs in other organisms and have highly reduced secondary structures. At the same time, nuclear encoded mt-ribosomal proteins have undergone expansions, likely to compensate for the reductions in mt-rRNA. The unusual features identified in M. leidyi mtDNA make this organism an interesting system for the study of various aspects of mitochondrial biology, particularly protein and tRNA import and mt-ribosome structures, and add to its value as an emerging model species. Furthermore, the fast-evolving M. leidyi mtDNA should be a convenient molecular marker for species-and population-level studies.
C1 [Pett, Walker; Lavrov, Dennis V.] Iowa State Univ, Dept Ecol Evolut & Organismal Biol, Ames, IA 50010 USA.
[Ryan, Joseph F.; Mullikin, James C.; Baxevanis, Andreas D.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Pang, Kevin; Martindale, Mark Q.] Univ Hawaii, Pacific Biosci Res Ctr, Kewalo Marine Lab, Honolulu, HI 96813 USA.
RP Lavrov, DV (reprint author), Iowa State Univ, Dept Ecol Evolut & Organismal Biol, Ames, IA 50010 USA.
EM dlavrov@iastate.edu
OI Lavrov, Dennis/0000-0002-2745-1704
FU National Science Foundation [DEB-0828783]; National Human Genome
Research Institute, National Institutes of Health
FX This work was supported by the DEB-0828783 grant from the National
Science Foundation. This work was also supported in part by the
Intramural Research Program of the National Human Genome Research
Institute, National Institutes of Health. The authors report no conflict
of interest. The authors alone are responsible for the content and
writing of the paper.
NR 101
TC 36
Z9 37
U1 0
U2 14
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1940-1736
EI 1940-1744
J9 MITOCHONDR DNA
JI Mitochondrial DNA
PD AUG
PY 2011
VL 22
IS 4
BP 130
EP 142
DI 10.3109/19401736.2011.624611
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA 839TW
UT WOS:000296393300016
PM 21985407
ER
PT J
AU Ross, JL
Quigley, CA
Cao, D
Feuillan, P
Kowal, K
Chipman, JJ
Cutler, GB
AF Ross, Judith L.
Quigley, Charmian A.
Cao, Dachuang
Feuillan, Penelope
Kowal, Karen
Chipman, John J.
Cutler, Gordon B., Jr.
TI Growth Hormone Plus Childhood Low-Dose Estrogen in Turner Syndrome
EDITORIAL COMMENT
SO OBSTETRICAL & GYNECOLOGICAL SURVEY
LA English
DT Editorial Material
C1 [Ross, Judith L.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
Alfred I DuPont Hosp Children, Wilmington, DE USA.
Lilly Res Labs, Indianapolis, IN USA.
NICHHD, Bethesda, MD 20892 USA.
RP Ross, JL (reprint author), Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
NR 1
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7828
J9 OBSTET GYNECOL SURV
JI Obstet. Gynecol. Surv.
PD AUG
PY 2011
VL 66
IS 8
BP 486
EP 487
DI 10.1097/OGX.0b013e3182248035
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 842MZ
UT WOS:000296604900011
ER
PT J
AU Rariy, CM
Ratcliffe, SJ
Weinstein, R
Bhasin, S
Blackman, MR
Cauley, JA
Robbins, J
Zmuda, JM
Harris, TB
Cappola, AR
AF Rariy, Chevon M.
Ratcliffe, Sarah J.
Weinstein, Rachel
Bhasin, Shalender
Blackman, Marc R.
Cauley, Jane A.
Robbins, John
Zmuda, Joseph M.
Harris, Tamara B.
Cappola, Anne R.
TI Higher Serum Free Testosterone Concentration in Older Women Is
Associated With Greater Bone Mineral Density, Lean Body Mass, and Total
Fat Mass: The Cardiovascular Health Study EDITORIAL COMMENT
SO OBSTETRICAL & GYNECOLOGICAL SURVEY
LA English
DT Editorial Material
C1 [Rariy, Chevon M.] Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA.
Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
Boston Univ, Sch Med, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA.
Washington DC Vet Affairs Med Ctr, Res Serv, Washington, DC USA.
Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
Univ Calif Davis, Div Gen Internal Med, Davis, CA 95616 USA.
NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Rariy, CM (reprint author), Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA.
NR 1
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7828
J9 OBSTET GYNECOL SURV
JI Obstet. Gynecol. Surv.
PD AUG
PY 2011
VL 66
IS 8
BP 492
EP 493
DI 10.1097/OGX.0b013e31823521f5
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 842MZ
UT WOS:000296604900014
ER
PT J
AU Esfandiari, A
Shoaib, M
Hogarth, L
Panlilio, L
AF Esfandiari, A.
Shoaib, M.
Hogarth, L.
Panlilio, L.
TI ESTABLISHING PAVLOVIAN TO INSTRUMENTAL TRANSFER (PIT) WITH INTRAVENOUS
NICOTINE AND SUCROSE IN RATS
SO JOURNAL OF PSYCHOPHARMACOLOGY
LA English
DT Meeting Abstract
CT Summer Meeting of the British-Association-for-Psychopharmacology
CY JUL 24-27, 2011
CL Harrogate, ENGLAND
SP British Assoc Psychopharmacol
C1 [Esfandiari, A.] Univ Newcastle Tyne, Inst Neurosci, Sch Biomed Sci, Sch Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
[Hogarth, L.] Univ Nottingham, Sch Psychol, Nottingham NG7 2RD, England.
[Panlilio, L.] NIDA, IRP, Baltimore, MD 21224 USA.
EM arman.esfandiari@ncl.ac.uk
NR 0
TC 0
Z9 0
U1 0
U2 2
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0269-8811
J9 J PSYCHOPHARMACOL
JI J. Psychopharmacol.
PD AUG
PY 2011
VL 25
IS 8
SU S
BP A44
EP A44
PG 1
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 837DG
UT WOS:000296170700123
ER
PT J
AU Insel, T
AF Insel, T.
TI NO HEALTH WITHOUT MENTAL HEALTH
SO JOURNAL OF PSYCHOPHARMACOLOGY
LA English
DT Meeting Abstract
CT Summer Meeting of the British-Association-for-Psychopharmacology
CY JUL 24-27, 2011
CL Harrogate, ENGLAND
SP British Assoc Psychopharmacol
C1 [Insel, T.] NIMH, Bethesda, MD 20892 USA.
EM tinsel@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 2
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0269-8811
J9 J PSYCHOPHARMACOL
JI J. Psychopharmacol.
PD AUG
PY 2011
VL 25
IS 8
SU S
BP A78
EP A78
PG 1
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 837DG
UT WOS:000296170700220
ER
PT J
AU Norman, NA
Hogarth, L
Panlilio, L
Shoaib, M
AF Norman, N. A.
Hogarth, L.
Panlilio, L.
Shoaib, M.
TI ESTABLISHING CONCURRENT CHOICE PROCEDURES WITH INTRAVENOUS NICOTINE AND
SUCROSE IN RATS
SO JOURNAL OF PSYCHOPHARMACOLOGY
LA English
DT Meeting Abstract
CT Summer Meeting of the British-Association-for-Psychopharmacology
CY JUL 24-27, 2011
CL Harrogate, ENGLAND
SP British Assoc Psychopharmacol
C1 [Norman, N. A.; Shoaib, M.] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
[Hogarth, L.] Univ Nottingham, Sch Psychol, Nottingham NG7 2RD, England.
[Panlilio, L.] NIDA, IRP, Baltimore, MD 21224 USA.
EM nicole.norman@kcl.ac.uk
NR 0
TC 0
Z9 0
U1 0
U2 2
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0269-8811
J9 J PSYCHOPHARMACOL
JI J. Psychopharmacol.
PD AUG
PY 2011
VL 25
IS 8
SU S
BP A46
EP A46
PG 1
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 837DG
UT WOS:000296170700129
ER
PT J
AU Zarate, CA
AF Zarate, C. A.
TI MODULATING THE GLUTAMATERGIC SYSTEM: A PROMISING AVENUE FOR DEVELOPING
NEW TREATMENTS FOR MOOD DISORDERS
SO JOURNAL OF PSYCHOPHARMACOLOGY
LA English
DT Meeting Abstract
CT Summer Meeting of the British-Association-for-Psychopharmacology
CY JUL 24-27, 2011
CL Harrogate, ENGLAND
SP British Assoc Psychopharmacol
C1 [Zarate, C. A.] NIMH, Intramural Res Program, Bethesda, MD 20892 USA.
EM zaratec@mail.nih.gov
NR 0
TC 0
Z9 0
U1 1
U2 2
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0269-8811
J9 J PSYCHOPHARMACOL
JI J. Psychopharmacol.
PD AUG
PY 2011
VL 25
IS 8
SU S
BP A3
EP A3
PG 1
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 837DG
UT WOS:000296170700009
ER
PT J
AU Caldecott, KW
Bohr, VA
McKinnon, PJ
AF Caldecott, Keith W.
Bohr, Vilhelm A.
McKinnon, Peter J.
TI 3rd International Genome Dynamics in Neuroscience Conference: "DNA
repair and neurological disease"
SO MECHANISMS OF AGEING AND DEVELOPMENT
LA English
DT Editorial Material
ID STRAND BREAK REPAIR; MITOCHONDRIAL-DNA; GENETIC-DISEASE; DAMAGE;
NEURODEGENERATION; DEFICIENCY; NEURONS
C1 [Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21042 USA.
[Caldecott, Keith W.] Univ Sussex, Genome Damage & Stabil Ctr, Brighton BN1 9RQ, E Sussex, England.
[McKinnon, Peter J.] St Jude Childrens Hosp, Dept Genet, Memphis, TN 38105 USA.
RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21042 USA.
EM k.w.caldecott@sussex.ac.uk; BohrV@grc.nia.nih.gov;
peter.mckinnon@stjude.org
FU Intramural NIH HHS [ZIA AG000729-22]
NR 18
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0047-6374
J9 MECH AGEING DEV
JI Mech. Ageing Dev.
PD AUG-SEP
PY 2011
VL 132
IS 8-9
SI SI
BP 353
EP 354
DI 10.1016/j.mad.2011.07.006
PG 2
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 836RF
UT WOS:000296128100001
PM 21820005
ER
PT J
AU Yang, JL
Sykora, P
Wilson, DM
Mattson, MP
Bohr, VA
AF Yang, Jenq-Lin
Sykora, Peter
Wilson, David M., III
Mattson, Mark P.
Bohr, Vilhelm A.
TI The excitatory neurotransmitter glutamate stimulates DNA repair to
increase neuronal resiliency
SO MECHANISMS OF AGEING AND DEVELOPMENT
LA English
DT Article; Proceedings Paper
CT 3rd International Genome Dynamics in Neuroscience Conference on DNA
Repair and Neurological Disease
CY JUL 18-21, 2010
CL Brighton, ENGLAND
DE Glutamate; Excitotoxicity; Oxidative DNA damage; APE1; Neurodegenerative
diseases
ID BASE EXCISION-REPAIR; AMYOTROPHIC-LATERAL-SCLEROSIS; INCREASED OXIDATIVE
DAMAGE; NF-KAPPA-B; POLYMERASE-BETA; HIPPOCAMPAL-NEURONS;
HUNTINGTONS-DISEASE; CREB PHOSPHORYLATION; PARKINSONS-DISEASE;
ALZHEIMERS-DISEASE
AB Glutamate is the most abundant excitatory neurotransmitter in the vertebrate central nervous system and plays an important role in synaptic plasticity required for learning and memory. Activation of glutamate ionotropic receptors promptly triggers membrane depolarization and Ca(2+) influx, resulting in the activation of several different protein kinases and transcription factors. For example, glutamate-mediated Ca(2+) influx activates Ca(2+)/calmodulin-dependent kinase, protein kinase C, and mitogen activated protein kinases resulting in activation of transcription factors such as cyclic AMP response element binding protein (CREB). Abnormally prolonged exposure to glutamate causes neuronal injury, and such "excitotoxicity" has been implicated in many acute and chronic diseases including ischemic stroke, epilepsy, amyotrophic lateral sclerosis, Alzheimer's, Huntington's and Parkinson's diseases. Interestingly, although glutamate-induced Ca(2+) influx can cause DNA damage by a mitochondrial reactive oxygen species-mediated mechanism, the Ca(2+) simultaneously activates CREB, resulting in upregulation of the DNA repair and redox protein apuriniciapyrimidinic endonuclease 1. Here, we review connections between physiological or aberrant glutamate receptor activation, Ca(2+)-mediated signaling, oxidative DNA damage and repair efficiency, and neuronal vulnerability. We conclude that glutamate signaling involves an adaptive cellular stress response pathway that enhances DNA repair capability, thereby protecting neurons against injury and disease. Published by Elsevier Ireland Ltd.
C1 [Yang, Jenq-Lin; Sykora, Peter; Wilson, David M., III; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, Intramural Res Program, Baltimore, MD 21224 USA.
[Mattson, Mark P.] NIA, Lab Neurosci, Intramural Res Program, Baltimore, MD 21224 USA.
RP Bohr, VA (reprint author), 251 Bayview Blvd,Ste 100, Baltimore, MD 21224 USA.
EM yangj2@mail.nih.gov; sykorap@mail.nih.gov; mattsonm@grc.nia.nih.gov;
bohrv@grc.nia.nih.gov
RI Mattson, Mark/F-6038-2012;
OI Yang, Jenq-Lin/0000-0002-9897-8087
FU Intramural NIH HHS [Z01 AG000735-12]
NR 81
TC 26
Z9 29
U1 0
U2 2
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0047-6374
J9 MECH AGEING DEV
JI Mech. Ageing Dev.
PD AUG-SEP
PY 2011
VL 132
IS 8-9
SI SI
BP 405
EP 411
DI 10.1016/j.mad.2011.06.005
PG 7
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 836RF
UT WOS:000296128100008
PM 21729715
ER
PT J
AU Basuli, F
Wu, HT
Li, CH
Shi, ZD
Sulima, A
Griffiths, GL
AF Basuli, Falguni
Wu, Haitao
Li, Changhui
Shi, Zhen-Dan
Sulima, Agnieszka
Griffiths, Gary L.
TI A first synthesis of F-18-radiolabeled lapatinib: a potential tracer for
positron emission tomographic imaging of ErbB1/ErbB2 tyrosine kinase
activity
SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS
LA English
DT Article
DE Radiolabeling; Fluorine-18; meta-[F-18]benzylbromide; [F-18]Lapatinib
ID GROWTH-FACTOR RECEPTOR; BREAST-CANCER; INHIBITOR; EGFR; THERAPY;
COMBINATION; EXPRESSION; GW572016; AGENTS; TUMORS
AB Fluorine-18-labeled lapatinib has been successfully synthesized for the first time by the reaction of a dimethylformamide solution of meta-[F-18]fluorobenzylbromide with a Boc-protected lapatinib precursor fragment. The reaction proceeded in the presence of K2CO3 at 110 degrees C for 10 min in a microwave and was followed by Boc-group deprotection with trifluoroacetic acid. The overall radiochemical yield of the reaction starting from the radiofluorination of the iodonium salt was 8-12% (uncorrected, n=6) in a 140-min synthesis time.
C1 [Basuli, Falguni; Wu, Haitao; Li, Changhui; Shi, Zhen-Dan; Sulima, Agnieszka; Griffiths, Gary L.] NHLBI, Imaging Probe Dev Ctr, NIH, Rockville, MD 20850 USA.
RP Griffiths, GL (reprint author), NHLBI, Imaging Probe Dev Ctr, NIH, Rockville, MD 20850 USA.
EM griffithsgl@mail.nih.gov
FU National Institutes of Health through Roadmap for Medical Research
Initiative
FX The authors would like to thank Christine Enders for her excellent
technical assistance. This study was funded by the National Institutes
of Health through its 2004 Roadmap for Medical Research Initiative.
NR 37
TC 12
Z9 12
U1 1
U2 21
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0362-4803
J9 J LABELLED COMPD RAD
JI J. Label. Compd. Radiopharm.
PD AUG
PY 2011
VL 54
IS 9-10
BP 633
EP 636
DI 10.1002/jlcr.1898
PG 4
WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry,
Analytical
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 833RB
UT WOS:000295901500009
ER
PT J
AU Barker, A
AF Barker, Anna
TI Q&A: Anna Barker on The Cancer Genome Atlas
SO CANCER DISCOVERY
LA English
DT Editorial Material
C1 NCI, Bethesda, MD 20892 USA.
RP Barker, A (reprint author), NCI, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 2159-8274
J9 CANCER DISCOV
JI Cancer Discov.
PD AUG
PY 2011
VL 1
IS 3
BP 193
EP 193
DI 10.1158/2159-8290.CD-ND11-03
PG 1
WC Oncology
SC Oncology
GA 832DY
UT WOS:000295783300006
PM 22586560
ER
PT J
AU Van Waes, C
AF Van Waes, Carter
TI Targeting NF-kappa B in Mouse Models of Lung Adenocarcinoma
SO CANCER DISCOVERY
LA English
DT Editorial Material
ID NECK-CANCER; BORTEZOMIB; HEAD; ACTIVATOR
AB Xue et al. demonstrate response and increased survival but development of acquired resistance to proteasome and inhibitor-kappa B kinase inhibitors targeting NF-kappa B activation in adenocarcinomas of Kras-activated, p53-deficient mice. Cancer Discovery; 1(3):200-2. (C) 2011 AACR.
C1 Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, Clin Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Van Waes, C (reprint author), Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, Clin Res Ctr, NIH, Room 4-2732,10 Ctr Dr, Bethesda, MD 20892 USA.
EM vanwaesc@nidcd.nih.gov
FU Intramural NIH HHS [ZIA DC000016-19]
NR 10
TC 2
Z9 2
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 2159-8274
J9 CANCER DISCOV
JI Cancer Discov.
PD AUG
PY 2011
VL 1
IS 3
BP 200
EP 202
DI 10.1158/2159-8290.CD-11-0159
PG 3
WC Oncology
SC Oncology
GA 832DY
UT WOS:000295783300015
PM 22586569
ER
PT J
AU Luco, RF
Misteli, T
AF Luco, Reini F.
Misteli, Tom
TI More than a splicing code: integrating the role of RNA, chromatin and
non-coding RNA in alternative splicing regulation
SO CURRENT OPINION IN GENETICS & DEVELOPMENT
LA English
DT Review
ID POLYMERASE-II; IN-VIVO; TRANSCRIPTION ELONGATION; EXONS; ORGANIZATION;
RECRUITMENT; EXPRESSION; SIGNATURES; CELLS
AB Large portions of the genome undergo alternative pre-mRNA splicing in often intricate patterns. Alternative splicing regulation requires extensive control mechanisms since errors can have deleterious consequences and may lead to developmental defects and disease. Recent work has identified a complex network of regulatory RNA elements which guide splicing decisions. In addition, the discovery that transcription and splicing are intimately coupled has opened up new directions into alternative splicing regulation. Work at the interface of chromatin and RNA biology has revealed unexpected molecular links between histone modifications, the transcription machinery, and non-coding RNAs (ncRNAs) in the determination of alternative splicing patterns.
C1 [Luco, Reini F.; Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA.
RP Luco, RF (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
EM fernamar@mail.nih.gov
NR 50
TC 49
Z9 52
U1 0
U2 24
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-437X
J9 CURR OPIN GENET DEV
JI Curr. Opin. Genet. Dev.
PD AUG
PY 2011
VL 21
IS 4
BP 366
EP 372
DI 10.1016/j.gde.2011.03.004
PG 7
WC Cell Biology; Genetics & Heredity
SC Cell Biology; Genetics & Heredity
GA 826JZ
UT WOS:000295351700002
PM 21497503
ER
PT J
AU Johnson, TV
Bull, ND
Martin, KR
AF Johnson, Thomas V.
Bull, Natalie D.
Martin, Keith R.
TI Neurotrophic factor delivery as a protective treatment for glaucoma
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE glaucoma; neurotrophic factor; neurotrophin; neuroprotection; slow
release; gene therapy; cell transplantation
ID RETINAL GANGLION-CELLS; MESENCHYMAL STEM-CELLS; INTRAOCULAR-PRESSURE
ELEVATION; LEBERS CONGENITAL AMAUROSIS; LOADED BIODEGRADABLE
MICROSPHERES; RETROGRADE AXOPLASMIC-TRANSPORT; PROMOTE FUNCTIONAL
RECOVERY; OPTIC-NERVE TRANSECTION; MARROW STROMAL CELLS; OPEN-ANGLE
GLAUCOMA
AB Glaucoma is a progressive optic neuropathy and a major cause of visual impairment worldwide. Neuroprotective therapies for glaucoma aim to ameliorate retinal ganglion cell degeneration through direct or indirect action on these neurons. Neurotrophic factor (NTF) delivery is a key target for the development of potential neuroprotective glaucoma treatments. This article will critically summarize the evidence that NTF deprivation and/or dysfunction plays a role in the pathogenesis of glaucoma. Experimental support for the neuroprotective potential of NTF supplementation in animal models of glaucoma will be reviewed, in particular for brain-derived neurotrophic factor, ciliary neurotrophic factor, and glial cell line-derived neurotrophic factor. Finally, the challenges of clinical translation will be considered with an emphasis on the most promising NTF delivery strategies including slow-release drug delivery, gene therapy, and cell transplantation. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Johnson, Thomas V.; Bull, Natalie D.; Martin, Keith R.] Univ Cambridge, Ctr Brain Repair, Cambridge CB2 0PY, England.
[Johnson, Thomas V.; Bull, Natalie D.; Martin, Keith R.] Univ Cambridge, Dept Ophthalmol, Cambridge CB2 0PY, England.
[Johnson, Thomas V.] NEI, Mol Mech Glaucoma Sect, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Martin, KR (reprint author), Univ Cambridge, Ctr Brain Repair, Forvie Site,Robinson Way, Cambridge CB2 0PY, England.
EM krgm2@cam.ac.uk
RI Johnson, Thomas/C-9351-2011
OI Johnson, Thomas/0000-0002-5372-5457
FU National Institutes of Health; Gates-Cambridge Trust; Fight for Sight
(UK); GSK; Cambridge University Hospitals NHS Foundation Trust; Jukes
Glaucoma Research Fund; National Eye Institute
FX TVJ is supported by a National Institutes of Health Ox Cam Scholarship
and the Gates-Cambridge Trust, NDB is supported by Fight for Sight (UK),
KRM is supported by a GSK Clinician Scientist Fellowship. This work was
supported by Cambridge University Hospitals NHS Foundation Trust, the
Jukes Glaucoma Research Fund, and the National Eye Institute Intramural
Research Program.
NR 106
TC 35
Z9 35
U1 0
U2 9
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
J9 EXP EYE RES
JI Exp. Eye Res.
PD AUG
PY 2011
VL 93
IS 2
SI SI
BP 196
EP 203
DI 10.1016/j.exer.2010.05.016
PG 8
WC Ophthalmology
SC Ophthalmology
GA 824KX
UT WOS:000295201900011
PM 20685205
ER
PT J
AU Purohit, V
Rapaka, R
Shurtleff, D
AF Purohit, Vishnudutt
Rapaka, Rao
Shurtleff, David
TI Drugs of Abuse, Dopamine, and HIV-Associated Neurocognitive
Disorders/HIV-Associated Dementia
SO MOLECULAR NEUROBIOLOGY
LA English
DT Article
DE Dopamine; Drugs of abuse; HIV/SIV; HAD/HAND; Macrophage/microglia;
gp120/Tat; Dopamine transporter
ID IMMUNODEFICIENCY-VIRUS TYPE-1; CENTRAL-NERVOUS-SYSTEM; FREELY MOVING
RATS; INFECTED RHESUS-MONKEYS; TAT PROTEIN; EXTRACELLULAR DOPAMINE;
NUCLEUS-ACCUMBENS; DIFFERENT REGIONS; SUBSTANTIA-NIGRA; OXIDATIVE DAMAGE
AB Although the incidence of HIV-associated dementia (HAD) has declined, HIV-associated neurocognitive disorders (HAND) remain a significant health problem despite use of highly active antiretroviral therapy. In addition, the incidence and/or severity of HAND/HAD are increased with concomitant use of drugs of abuse, such as cocaine, marijuana, and methamphetamine. Furthermore, exposure to most drugs of abuse increases brain levels of dopamine, which has been implicated in the pathogenesis of HIV. This review evaluates the potential role of dopamine in the potentiation of HAND/HAD by drugs of abuse. In the brain, multiplication of HIV in infected macrophages/microglia could result in the release of HIV proteins such as gp120 and Tat, which can bind to and impair dopamine transporter (DAT) functions, leading to elevated levels of dopamine in the dopaminergic synapses in the early asymptomatic stage of HIV infection. Exposure of HIV-infected patients to drugs of abuse, especially cocaine and methamphetamine, can further increase synaptic levels of dopamine via binding to and subsequently impairing the function of DAT. This accumulated synaptic dopamine can diffuse out and activate adjacent microglia through binding to dopamine receptors. The activation of microglia may result in increased HIV replication as well as increased production of inflammatory mediators such as tumor necrosis factor (TNF)-alpha and chemokines. Increased HIV replication can lead to increased brain viral load and increased shedding of HIV proteins, gp120 and Tat. These proteins, as well as TNF-alpha, can induce cell death of adjacent dopaminergic neurons via apoptosis. Autoxidation and metabolism of accumulated synaptic dopamine can lead to generation of reactive oxygen species (hydrogen peroxide), quinones, and semiquinones, which can also induce apoptosis of neurons. Increased cell death of dopaminergic neurons can eventually lead to dopamine deficit that may exacerbate the severity and/or accelerate the progression of HAND/HAD.
C1 [Purohit, Vishnudutt; Rapaka, Rao; Shurtleff, David] NIDA, Chem & Physiol Syst Res Branch, Div Basic Neurosci & Behav Res, NIH, Bethesda, MD 20892 USA.
RP Purohit, V (reprint author), NIDA, Chem & Physiol Syst Res Branch, Div Basic Neurosci & Behav Res, NIH, 6001 Execut Blvd,Room 4277,MSC 9555, Bethesda, MD 20892 USA.
EM vpurohit@nida.nih.gov
NR 77
TC 54
Z9 56
U1 4
U2 12
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0893-7648
J9 MOL NEUROBIOL
JI Mol. Neurobiol.
PD AUG
PY 2011
VL 44
IS 1
BP 102
EP 110
DI 10.1007/s12035-011-8195-z
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 825MR
UT WOS:000295282500010
PM 21717292
ER
PT J
AU Patel, S
Muallem, S
AF Patel, Sandip
Muallem, Shmuel
TI Acidic Ca2+ stores come to the fore
SO CELL CALCIUM
LA English
DT Editorial Material
DE Calcium; Acidic calcium stores; Acidocalcisomes; Vacuoles; Endosomes;
Lysosomes; Lysosome-related organelles; Secretory vesicles; Golgi; TRP
channels; Two-pore channels; TPCs; IP3 receptor; Ryanodine receptor;
Ca2+ ATPases; Ca2+/H+ exchangers; NAADP; Acute pancreatitis; Lysosomal
storage disorders; Protists; Trypanosomes; Plants; Yeast; Sea urchin;
Platelets; Pancreatic acinar cells
ID MUCOLIPIDOSIS TYPE-IV; SEA-URCHIN EGGS; ENDOPLASMIC-RETICULUM; CALCIUM;
NAADP; CHANNEL; RELEASE; CELLS; ORGANELLES; GOLGI
AB Changes in the concentration of cytosolic Ca2+ form the basis of a ubiquitous signal transduction pathway. Accumulating evidence implicates acidic organelles in the control of Ca2+ dynamics in organisms across phyla. In this special issue, we discuss Ca2+ signalling by these "acidic Ca2+ stores" which include acidocalcisomes, vacuoles, the endo-lysosomal system, lysosome-related organelles, secretory vesicles and the Golgi complex. Ca2+ release from these morphologically very different organelles is mediated by members of the TRP channel superfamily and two-pore channels. Inositol trisphosphate and ryanodine receptors which are traditionally viewed as endoplasmic reticulum Ca2+ release channels can also mobilize acidic Ca2+ stores. Ca2+ uptake into acidic Ca2+ stores is driven by Ca(2+)ATPases and Ca2+/H+ exchangers. In animal cells, the Ca2+-mobilizing messenger NAADP plays a central role in mediating Ca2+ signals from acidic Ca2+ stores through activation of two-pore channels. These signals are important for several physiological processes including muscle contraction and differentiation. Dysfunctional acidic Ca2+ stores have been implicated in diseases such as acute pancreatitis and lysosomal storage disorders. Acidic Ca2+ stores are therefore emerging as essential components of the Ca2+ signalling network and merit extensive further study. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Patel, Sandip] UCL, Dept Cell & Dev Biol, London WC1E 6BT, England.
[Muallem, Shmuel] NIDCR, Epithelial Signaling & Transport Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA.
RP Patel, S (reprint author), UCL, Dept Cell & Dev Biol, Mortimer St, London WC1E 6BT, England.
EM patel.s@ucl.ac.uk
RI Patel, Sandip/O-9591-2015
OI Patel, Sandip/0000-0001-7247-2013
NR 48
TC 34
Z9 34
U1 0
U2 5
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 AUG
PY 2011
VL 50
IS 2
SI SI
BP 109
EP 112
DI 10.1016/j.ceca.2011.03.009
PG 4
WC Cell Biology
SC Cell Biology
GA 823GT
UT WOS:000295111200001
PM 21497395
ER
PT J
AU Fairman, JW
Noinaj, N
Buchanan, SK
AF Fairman, James W.
Noinaj, Nicholas
Buchanan, Susan K.
TI The structural biology of beta-barrel membrane proteins: a summary of
recent reports
SO CURRENT OPINION IN STRUCTURAL BIOLOGY
LA English
DT Article
ID MITOCHONDRIAL OUTER-MEMBRANE; ANION-SELECTIVE CHANNEL; GRAM-NEGATIVE
BACTERIA; CRYSTAL-STRUCTURE; BIOGENESIS; COMPLEX; CRYSTALLIZATION; VDAC;
APOPTOSIS; BAMA
AB The outer membranes of Gram-negative bacteria, mitochondria, and chloroplasts all contain transmembrane beta-barrel proteins. These beta-barrel proteins serve essential functions in cargo transport and signaling and are also vital for membrane biogenesis. They have also been adapted to perform a diverse set of important cellular functions including acting as porins, transporters, enzymes, virulence factors and receptors. Recent structures of transmembrane beta-barrels include that of a full length autotransporter (EstA), a bacterial heme transporter complex (HasR), a bacterial porin in complex with several ligands (PorB), and the mitochondrial voltage-dependent anion channel (VDAC) from both mouse and human. These represent only a few of the interesting structures of beta-barrel membrane proteins recently elucidated. However, they demonstrate many of the advancements made within the field of transmembrane protein structure in the past few years.
C1 [Fairman, James W.; Noinaj, Nicholas; Buchanan, Susan K.] NIDDKD, NIH, Bethesda, MD 20892 USA.
RP Buchanan, SK (reprint author), NIDDKD, NIH, Bethesda, MD 20892 USA.
EM skbuchan@helix.nih.gov
FU NIH, National Institute of Diabetes and Digestive and Kidney Diseases
FX We thank K. Zeth for providing a homology model for Tom40. JWF, NN, and
SKB are supported by the Intramural Research Program of the NIH,
National Institute of Diabetes and Digestive and Kidney Diseases.
NR 54
TC 75
Z9 75
U1 4
U2 27
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-440X
J9 CURR OPIN STRUC BIOL
JI Curr. Opin. Struct. Biol.
PD AUG
PY 2011
VL 21
IS 4
BP 523
EP 531
DI 10.1016/j.sbi.2011.05.005
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 822TZ
UT WOS:000295073800013
PM 21719274
ER
PT J
AU Chuang, SC
Stolzenberg-Solomon, R
Ueland, PM
Vollset, SE
Midttun, O
Olsen, A
Tjonneland, A
Overvad, K
Boutron-Ruault, MC
Morois, S
Clavel-Chapelon, F
Teucher, B
Kaaks, R
Weikert, C
Boeing, H
Trichopoulou, A
Benetou, V
Naska, A
Jenab, M
Slimani, N
Romieu, I
Michaud, DS
Palli, D
Sieri, S
Panico, S
Sacerdote, C
Tumino, R
Skeie, G
Duell, EJ
Rodriguez, L
Molina-Montes, E
Huerta, JM
Larranaga, N
Gurrea, AB
Johansen, D
Manjer, J
Ye, WM
Sund, M
Peeters, PHM
Jeurnink, S
Wareham, N
Khaw, KT
Crowe, F
Riboli, E
Bueno-de-Mesquita, B
Vineis, P
AF Chuang, Shu-Chun
Stolzenberg-Solomon, Rachael
Ueland, Per Magne
Vollset, Stein Emil
Midttun, Oivind
Olsen, Anja
Tjonneland, Anne
Overvad, Kim
Boutron-Ruault, Marie-Christine
Morois, Sophie
Clavel-Chapelon, Francoise
Teucher, Birgit
Kaaks, Rudolf
Weikert, Cornelia
Boeing, Heiner
Trichopoulou, Antonia
Benetou, Vassiliki
Naska, Androniki
Jenab, Mazda
Slimani, Nadia
Romieu, Isabelle
Michaud, Dominique S.
Palli, Domenico
Sieri, Sabina
Panico, Salvatore
Sacerdote, Carlotta
Tumino, Rosario
Skeie, Guri
Duell, Eric J.
Rodriguez, Laudina
Molina-Montes, Esther
Maria Huerta, Jose
Larranaga, Nerea
Barricarte Gurrea, Aurelio
Johansen, Dorthe
Manjer, Jonas
Ye, Weimin
Sund, Malin
Peeters, Petra H. M.
Jeurnink, Suzanne
Wareham, Nicholas
Khaw, Kay-Tee
Crowe, Francesca
Riboli, Elio
Bueno-de-Mesquita, Bas
Vineis, Paolo
TI A U-shaped relationship between plasma folate and pancreatic cancer risk
in the European Prospective Investigation into Cancer and Nutrition
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Article
DE Folate; One-carbon metabolism; Pancreatic cancer; EPIC
ID MASS-SPECTROMETRY; MICROBIOLOGICAL ASSAY; COLORECTAL-CANCER; SWEDISH
WOMEN; MALE SMOKERS; DIETARY; SERUM; MEN; FORTIFICATION; HOMOCYSTEINE
AB Folate intake has shown an inverse association with pancreatic cancer; nevertheless, results from plasma measurements were inconsistent. The aim of this study is to examine the association between plasma total homocysteine, methionine, folate, cobalamin, pyridoxal 5'-phosphate, riboflavin, flavin mononucleotide and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). We conducted a nested case-control study in the EPIC cohort, which has an average of 9.6 years of follow-up (1992-2006), using 463 incident pancreatic cancer cases. Controls were matched to each case by center, sex, age (+/- 1 year), date (+/- 1 year) and time (+/- 3 h) at blood collection and fasting status. Conditional logistic regression was used to calculate the odds ratios (OR) and 95% confidence intervals (CI), adjusting for education, smoking status, plasma cotinine concentration, alcohol drinking, body mass index and diabetes status. We observed a U-shaped association between plasma folate and pancreatic cancer risk. The ORs for plasma folate <= 5, 5-10, 10-15 (reference), 15-20, and > 20 nmol/L were 1.58 (95% CI = 0.72-3.46), 1.39 (0.93-2.08), 1.0 (reference), 0.79 (0.52-1.21), and 1.34 (0.89-2.02), respectively. Methionine was associated with an increased risk in men (per quintile increment: OR = 1.17, 95% CI = 1.00-1.38) but not in women (OR = 0.91, 95% CI = 0.78-1.07; p for heterogeneity < 0.01). Our results suggest a U-shaped association between plasma folate and pancreatic cancer risk in both men and women. The positive association that we observed between methionine and pancreatic cancer may be sex dependent and may differ by time of follow-up. However, the mechanisms behind the observed associations warrant further investigation. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Chair Environm Epidemiol, London W2 1PG, England.
[Chuang, Shu-Chun; Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, MRC HPA Ctr Environm & Hlth, London W2 1PG, England.
[Stolzenberg-Solomon, Rachael] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Ueland, Per Magne] Univ Bergen, Pharmacol Sect, Inst Med, Bergen, Norway.
[Ueland, Per Magne] Haukeland Hosp, Lab Clin Biochem, N-5021 Bergen, Norway.
[Vollset, Stein Emil] Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway.
[Vollset, Stein Emil] Norwegian Inst Publ Hlth, Div Epidemiol, Bergen, Norway.
[Midttun, Oivind] Bevital AS, Bergen, Norway.
[Olsen, Anja; Tjonneland, Anne] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark.
[Overvad, Kim] Aarhus Univ, Sch Publ Hlth, Dept Epidemiol, DK-8000 Aarhus C, Denmark.
[Boutron-Ruault, Marie-Christine; Morois, Sophie; Clavel-Chapelon, Francoise] Ctr Res Epidemiol & Publ Hlth, INSERM, U1018, F-94805 Villejuif, France.
[Boutron-Ruault, Marie-Christine; Morois, Sophie; Clavel-Chapelon, Francoise] Paris S Univ, UMRS1018, F-94805 Villejuif, France.
[Weikert, Cornelia] German Inst Human Nutr, D-14558 Nuthetal, Germany.
[Boeing, Heiner] Deutsch Inst Ernahrungsforsch, Dept Epidemiol, Potsdam, Germany.
[Trichopoulou, Antonia; Benetou, Vassiliki; Naska, Androniki] Univ Athens, Sch Med, WHO Collaborating Ctr Food & Nutr Policies, Dept Hyg Epidemiol & Med Stat, GR-11527 Athens, Greece.
[Trichopoulou, Antonia] Hellen Hlth Fdn, Athens, Greece.
[Jenab, Mazda; Slimani, Nadia; Romieu, Isabelle] Int Agcy Res Canc, F-69372 Lyon, France.
[Michaud, Dominique S.] Brown Univ, Providence, RI 02912 USA.
[Palli, Domenico] Canc Res & Prevent Inst ISPO, Mol & Nutr Epidemiol Unit, Florence, Italy.
[Panico, Salvatore] Univ Naples Federico II, Dipartimento Med Clin & Sperimentale, Naples, Italy.
[Sacerdote, Carlotta] CPO Piemonte, Turin, Italy.
[Sacerdote, Carlotta; Vineis, Paolo] HuGeF Fdn, Turin, Italy.
[Tumino, Rosario] Civile MPArezzo Hosp ASP 7, Canc Registry & Histopathol Unit, Ragusa, Italy.
[Skeie, Guri] Univ Tromso, Dept Community Med, Tromso, Norway.
[Duell, Eric J.] ICO, Canc Epidemiol Res Programme, Unit Nutr Environm & Canc, Barcelona, Spain.
[Rodriguez, Laudina] Serv Salud Sanitarios, Jefa Secc Informac Sanitaria, Principado De Asturias, Asturias, Spain.
[Molina-Montes, Esther] Andalusian Sch Publ Hlth, Granada, Spain.
[Maria Huerta, Jose] Murcia Reg Hlth Author, Dept Epidemiol, Murcia, Spain.
[Barricarte Gurrea, Aurelio] Navarre Publ Hlth Inst, Pamplona, Spain.
[Johansen, Dorthe; Manjer, Jonas] Lund Univ, Dept Surg, Skane Univ Hosp Malmo, Malmo, Sweden.
[Ye, Weimin] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Ye, Weimin] Umea Univ, Med Biobank, Umea, Sweden.
[Sund, Malin] Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden.
[Sund, Malin] Umea Univ, Dept Surg, Umea, Sweden.
[Sund, Malin] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
[Peeters, Petra H. M.] Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
[Jeurnink, Suzanne; Bueno-de-Mesquita, Bas] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands.
[Jeurnink, Suzanne; Bueno-de-Mesquita, Bas] Univ Med Ctr Utrecht UMCU, Dept Gastroenterol & Hepatol, Utrecht, Netherlands.
[Wareham, Nicholas] MRC Epidemiol Unit, Cambridge, England.
[Khaw, Kay-Tee] Univ Cambridge, Cambridge, England.
[Crowe, Francesca] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England.
RP Vineis, P (reprint author), Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Chair Environm Epidemiol, St Marys Campus,Norfolk Pl, London W2 1PG, England.
EM p.vineis@imperial.ac.uk
RI Ueland, Per/C-7340-2013; Boutron Ruault, Marie-Christine/G-3705-2013;
Boutron, Marie-Christine/K-8168-2013; Chuang, Shu-Chun/N-3358-2013;
Clavel-Chapelon, Francoise/G-6733-2014; Michaud, Dominique/I-5231-2014;
Boutron-Ruault, Marie-Christine/H-3936-2014; Teucher,
Birgit/J-6380-2015; Huerta, Jose Maria/N-8654-2015; Sieri,
Sabina/K-4667-2016; Panico, Salvatore/K-6506-2016;
OI Sund, Malin/0000-0002-7516-9543; Skeie, Guri/0000-0003-2476-4251;
Sacerdote, Carlotta/0000-0002-8008-5096; PALLI,
Domenico/0000-0002-5558-2437; Huerta, Jose Maria/0000-0002-9637-3869;
Sieri, Sabina/0000-0001-5201-172X; Panico,
Salvatore/0000-0002-5498-8312; Duell, Eric J/0000-0001-5256-0163
FU World Cancer Research Fund (WCRF) [2008/51]; European Commission
(SANCO); Danish Cancer Society, Denmark; Ligue centre le Cancer, France;
Institut Gustave Roussy, France; Mutuelle Generale de l'Education
Nationale, France; Institut National de la Sante et de la Recherche
Medicale (INSERM), France; Hellenic Ministry of Health, Greece; Stavros
Niarchos Foundation, Greece; Hellenic Health Foundation, Greece; German
Cancer Aid, Cerman Cancer Research Cente, Germany; Federal Ministry of
Education and Research, Germany [01-EA-9401]; Italian Association for
Research on Cancer, Italy; National Research Council, Italy; Dutch
Ministry of Public Health, Welfare and Sports (VWS), Netherlands;
Netherlands Cancer Registry (NKR), Netherlands; LK Research Funds,
Netherlands; Dutch Prevention Funds, Netherlands; Dutch ZON (Zorg
Onderzoek Nederland), Netherlands; World Cancer Research Fund (WCRF),
Netherlands; Statistics Netherlands, Netherlands; Helga-Nordforsk center
of excellence in food, nutrition and health, Norway; Health Research
Fund (FIS) of the Spanish Ministry of Health, Spain [96/0032];
participating regional governments and institutions; Swedish Cancer
Society, Swedish Scientific Council, and Regional Government of Skane,
Sweden; Cancer Research UK and Medical Research Council, UK
FX The project is supported by World Cancer Research Fund (WCRF, Grant
Number:2008/51).The EPIC cohort is supported by the Europe Against
Cancer Program of the European Commission (SANCO). The individual
centres also received funding from:Denmark:Danish Cancer Society;
France:Ligue centre le Cancer, Institut Gustave Roussy, Mutuelle
Generale de l'Education Nationale, Institut National de la Sante et de
la Recherche Medicale (INSERM); Greece:Hellenic Ministry of Health, The
Stavros Niarchos Foundation and The Hellenic Health Foundation;
Germany:German Cancer Aid, Cerman Cancer Research Center, and Federal
Ministry of Education and Research (Grant 01-EA-9401); Italy:Italian
Association for Research on Cancer and The National Research Council;
The Netherlands:Dutch Ministry of Public Health, Welfare and Sports
(VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch
Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer
Research Fund (WCRF), Statistics Netherlands; Norway:Helga-Nordforsk
center of excellence in food, nutrition and health; Spain:Health
Research Fund (FIS) of the Spanish Ministry of Health (Exp 96/0032) and
the participating regional governments and institutions; Sweden:Swedish
Cancer Society, Swedish Scientific Council, and Regional Government of
Skane; UK: Cancer Research UK and Medical Research Council.
NR 30
TC 18
Z9 18
U1 0
U2 14
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD AUG
PY 2011
VL 47
IS 12
BP 1808
EP 1816
DI 10.1016/j.ejca.2011.02.007
PG 9
WC Oncology
SC Oncology
GA 822SW
UT WOS:000295070900007
PM 21411310
ER
PT J
AU Rosenfeld, S
AF Rosenfeld, Simon
TI Mathematical descriptions of biochemical networks: Stability,
stochasticity, evolution
SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY
LA English
DT Review
DE Biochemical networks; Dynamic stability; Stochasticity; Burstiness;
S-Systems; Systems biology
ID POWER-LAW APPROXIMATION; ESCHERICHIA-COLI; COMPLEX NETWORKS; SYSTEMS
ANALYSIS; GENE-EXPRESSION; CENTRAL DOGMA; TRANSCRIPTIONAL REGULATION;
DIFFERENTIAL-EQUATIONS; REGULATORY MECHANISMS; PROTEIN
AB In this paper, we review some fundamental aspects, as well as some new developments, in the emerging field of network biology. The focus of attention is placed on mathematical approaches to conceptual modeling of biomolecular networks with special emphasis on dynamic stability, stochasticity and evolution. Published by Elsevier Ltd.
C1 NCI, EPN, Rockville, MD 20852 USA.
RP Rosenfeld, S (reprint author), NCI, EPN, 6130 Execut Blvd,Rm 3108, Rockville, MD 20852 USA.
EM sr212a@nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 112
TC 11
Z9 11
U1 0
U2 17
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0079-6107
J9 PROG BIOPHYS MOL BIO
JI Prog. Biophys. Mol. Biol.
PD AUG
PY 2011
VL 106
IS 2
BP 400
EP 409
DI 10.1016/j.pbiomolbio.2011.03.003
PG 10
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 823UV
UT WOS:000295152900007
PM 21419158
ER
PT J
AU Baker, SG
Kramer, BS
AF Baker, Stuart G.
Kramer, Barnett S.
TI Systems biology and cancer: Promises and perils
SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY
LA English
DT Review
DE Bioinformatics; Microarrays; Reverse engineering; Receiver operating
characteristic curves
ID GENE REGULATORY NETWORKS; CLASSIFICATION; MICROARRAYS; CURVES;
CARCINOGENESIS; PERSPECTIVE; PREDICTION
AB Systems biology uses systems of mathematical rules and formulas to study complex biological phenomena. In cancer research there are three distinct threads in systems biology research: modeling biology or biophysics with the goal of establishing plausibility or obtaining insights, modeling based on statistics, bioinformatics, and reverse engineering with the goal of better characterizing the system, and modeling with the goal of clinical predictions. Using illustrative examples we discuss these threads in the context of cancer research. Published by Elsevier Ltd.
C1 [Baker, Stuart G.] NCI, Canc Prevent Div, EPN 3131, Bethesda, MD 20892 USA.
[Kramer, Barnett S.] NCI, Off Commun & Educ, Bethesda, MD 20892 USA.
RP Baker, SG (reprint author), NCI, Canc Prevent Div, EPN 3131, 6130 Execut Blvd,MSC 7354, Bethesda, MD 20892 USA.
EM sb16i@nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 26
TC 11
Z9 12
U1 0
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0079-6107
J9 PROG BIOPHYS MOL BIO
JI Prog. Biophys. Mol. Biol.
PD AUG
PY 2011
VL 106
IS 2
BP 410
EP 413
DI 10.1016/j.pbiomolbio.2011.03.002
PG 4
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 823UV
UT WOS:000295152900008
PM 21419159
ER
PT J
AU Abrams, A
Akahata, Y
Jacobson, S
AF Abrams, Anna
Akahata, Yoshimi
Jacobson, Steven
TI The Prevalence and Significance of HTLV-I/II Seroindeterminate Western
Blot Patterns
SO VIRUSES-BASEL
LA English
DT Review
DE HTLV-I; seroindeterminate; Western blot
ID CELL LYMPHOTROPIC VIRUS; LINKED-IMMUNOSORBENT-ASSAY; I-ASSOCIATED
MYELOPATHY; PLASMODIUM-FALCIPARUM; SAO-PAULO; CROSS-REACTIVITY;
CENTRAL-AFRICA; TYPE-1 HTLV-1; DONORS; INFECTION
AB Human T-lymphotropic virus type I (HTLV-I) infects an estimated 15-20 million persons worldwide. A number of diseases have been associated with the virus including adult T-cell leukemia (ATL), HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), HTLV-I uveitis, and HTLV-I-associated infective dermatitis. Once it was shown that there is an increased risk for developing HAM/TSP associated with blood transfusion, screening for HTLV-1 among blood banks was implemented in Japan, United States, France, and the Netherlands. This process includes detection by an enzyme immunoassay (EIA) followed by a confirmatory Western blot (WB) in which recombinant proteins specific for HTLV-I Env glycoproteins are incorporated into WB strips. HTLV-I seropositive results are defined by the presence of antibodies against either gp46 or gp62/68 (both Env protein bands) and either p19, p24, or p53 (one of the gag bands). HTLV-II seropositivity is confirmed by the presence of rgp46-II. However, numerous cases have been documented in which serum samples are reactive by EIA, but an incomplete banding pattern is displayed by subsequent confirmatory WB. Although the significance of these HTLV-I/II seroindeterminates is unclear, it may suggest a much higher incidence of exposure to HTLV-I/II than previously estimated.
C1 [Abrams, Anna; Akahata, Yoshimi; Jacobson, Steven] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
RP Abrams, A (reprint author), NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
EM abramsan@mail.nih.gov; akahatay@ninds.nih.gov; JacobsonS@ninds.nih.gov
NR 39
TC 9
Z9 10
U1 1
U2 4
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1999-4915
J9 VIRUSES-BASEL
JI Viruses-Basel
PD AUG
PY 2011
VL 3
IS 8
BP 1320
EP 1331
DI 10.3390/v3081320
PG 12
WC Virology
SC Virology
GA 824OR
UT WOS:000295212100002
PM 21994781
ER
PT J
AU Poss, M
AF Poss, Mary
TI Virus Dynamics and Evolution: Bridging Scales and Disciplines
SO VIRUSES-BASEL
LA English
DT Editorial Material
ID TRANSMISSION; INFECTION; MODELS
C1 [Poss, Mary] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Poss, Mary] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Poss, M (reprint author), Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
EM mposs@bx.psu.edu
NR 11
TC 1
Z9 2
U1 1
U2 4
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1999-4915
J9 VIRUSES-BASEL
JI Viruses-Basel
PD AUG
PY 2011
VL 3
IS 8
BP 1432
EP 1438
DI 10.3390/v3081432
PG 7
WC Virology
SC Virology
GA 824OR
UT WOS:000295212100010
PM 21994789
ER
PT J
AU Gualco, G
Domeny-Duarte, P
Chioato, L
Barber, G
Natkunam, Y
Bacchi, CE
AF Gualco, Gabriela
Domeny-Duarte, Pollyanna
Chioato, Lucimara
Barber, Glen
Natkunam, Yasodha
Bacchi, Carlos E.
TI Clinicopathologic and Molecular Features of 122 Brazilian Cases of Nodal
and Extranodal NK/T-Cell Lymphoma, Nasal Type, With EBV Subtyping
Analysis
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE NK/T cell lymphoma; nasal type; extranasal T/NK; angiocentric lymphoma;
Brazil; EBV; cytotoxic granules
ID EPSTEIN-BARR-VIRUS; NATURAL-KILLER-CELL; PERIPHERAL T-CELL;
NON-HODGKINS-LYMPHOMA; AGGRESSIVE NEOPLASM; BURKITTS-LYMPHOMA; MIDLINE
GRANULOMA; T/NK LYMPHOMAS; HIGH-FREQUENCY; INFECTION
AB Extranodal natural killer/T-cell lymphoma, nasal type (NK/TCL) is more prevalent in Asia and in some areas of South and Central America, but it is rarely seen in the United States and Europe. In this study, a series of 122 cases of NK/TCL from Brazil was analyzed with respect to clinicopathologic features. Clinical characteristics and geographic distribution were evaluated in 97 cases of nasal/nasopharyngeal region and 23 cases in extranasal sites including 6 nodal cases. Clinical staging and follow-up information was available in a subset of 21 patients. All cases harbored Epstein-Barr virus (EBV), 95% and 85% expressed cytoplasmic CD3 and CD56, respectively, and all cases were positive for at least 1 marker for cytotoxic granules. The global distribution of EBV subtypes showed predominance of strain subtype A, 89%, and subtype B, 11%. No dual infections were detected. TCR-gamma TCR-gene rearrangement was observed in 7 cases; all of them extranodal. Three of TCR-gamma(+) cases showed EBV subtype A. Two TCR-gamma(+)/CD56(+) cases showed EBV subtype B. Geographic distribution of NK/TCL showed higher frequency in the southeast and northeast regions of Brazil. Striking differences among geographic regions were seen with the vast majority of EBV subtype B (86%) occurring in the south and southeast regions.
C1 [Barber, Glen] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Barber, Glen] Fogarty Int Ctr, Sylvester Canc Ctr, Miami, FL USA.
[Natkunam, Yasodha] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA.
RP Bacchi, CE (reprint author), Rua Major Leonidas Cardoso 739, BR-18602010 Botucatu, SP, Brazil.
EM bacchi@conspat.com.br
NR 59
TC 45
Z9 52
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0147-5185
J9 AM J SURG PATHOL
JI Am. J. Surg. Pathol.
PD AUG
PY 2011
VL 35
IS 8
BP 1195
EP 1203
DI 10.1097/PAS.0b013e31821ec4b5
PG 9
WC Pathology; Surgery
SC Pathology; Surgery
GA 792GD
UT WOS:000292728200014
PM 21716086
ER
PT J
AU Garcia-Herrera, A
Song, JY
Chuang, SS
Villamor, N
Colomo, L
Pittaluga, S
Alvaro, T
Rozman, M
Gonzalez, JD
Arrunategui, AM
Fernandez, E
Gonzalvo, E
Estrach, T
Colomer, D
Raffeld, M
Gaulard, P
Campo, E
Jaffe, ES
Martinez, A
AF Garcia-Herrera, Adriana
Song, Joo Y.
Chuang, Shih-Sung
Villamor, Neus
Colomo, Luis
Pittaluga, Stefania
Alvaro, Tomas
Rozman, Maria
de Anda Gonzalez, Jazmin
Maria Arrunategui, Ana
Fernandez, Eva
Gonzalvo, Elena
Estrach, Teresa
Colomer, Dolors
Raffeld, Mark
Gaulard, Philippe
Campo, Elias
Jaffe, Elaine S.
Martinez, Antonio
TI Nonhepatosplenic gamma delta T-cell Lymphomas Represent a Spectrum of
Aggressive Cytotoxic T-cell Lymphomas With a Mainly Extranodal
Presentation
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE gamma delta T-cell lymphomas; gamma delta T-cell receptor; alpha beta
T-cell receptor; cutaneous gamma delta T-cell lymphoma; hepatosplenic
T-cell lymphoma
ID DISTINCT CLINICOPATHOLOGICAL ENTITY; NK-CELL; INTRAEPITHELIAL
LYMPHOCYTES; RECEPTOR; SKIN; CLASSIFICATION; ENTEROPATHY; EXPRESSION;
FEATURES; SUBSET
AB gamma delta T cells represent a minor T-cell subset that is mainly distributed in mucosal surfaces. Two distinct lymphomas derived from these cells have been recognized: hepatosplenic gamma delta T-cell lymphoma (HSTL) and primary cutaneous gamma delta T-cell lymphoma (PCGD-TCL). However, whether other anatomic sites may also be involved and whether they represent a spectrum of the same disease are not well studied. The lack of T-cell receptor (TCR)beta expression has been used to infer a gamma delta origin when other methods are not available. We studied 35 T-cell tumors suspected to be gamma delta TCL using monoclonal antibodies reactive with TCR delta or gamma in paraffin sections. We were able to confirm gd chain expression in 22 of 35 cases. We identified 8 PCGD-TCLs, 6 HSTLs, and 8 gamma delta TCLs without hepatosplenic or cutaneous involvement involving mainly extranodal sites. Two such cases were classified as enteropathy-associated T-cell lymphoma, type II. The other gamma delta TCL presented in the intestine, lung, tongue, orbit, and lymph node. In addition, we observed 13 cases with mainly extranodal involvement that lacked any TCR expression ("TCR silent"). In all cases, a natural killer cell origin was excluded. In conclusion, the lack of TCR beta expression does not always predict gamma delta-T-cell derivation, as TCR silent cases may be found. The recognition of gamma delta TCL presenting in extranodal sites other than skin and liver/spleen expands the clinical spectrum of these tumors. However, non-HSTL gamma delta TCL do not seem to represent a single entity. The relationship of these tumors with either HSTL or PCGD-TCL requires further study.
C1 [Martinez, Antonio] Hosp Clin Barcelona, Pathol Lab, Hematopathol Sect, Dept Pathol,IDIBAPS, E-08036 Barcelona, Spain.
[Estrach, Teresa] Univ Barcelona, Hosp Clin, Dept Dermatol, Barcelona, Spain.
[Alvaro, Tomas] Hosp Verge Cinta, Dept Pathol, Tortosa, Spain.
[Song, Joo Y.; Pittaluga, Stefania; Raffeld, Mark; Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, Bethesda, MD 20892 USA.
[Chuang, Shih-Sung] Chi Mei Med Ctr, Dept Pathol, Tainan, Taiwan.
[Chuang, Shih-Sung] Taipei Med Univ, Taipei, Taiwan.
[de Anda Gonzalez, Jazmin] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico City, DF, Mexico.
[Maria Arrunategui, Ana] Fdn Valle Lili, Cali, Colombia.
[Gaulard, Philippe] Univ Paris Est, Dept Pathol, Hosp Henri Mondor, INSERM,U955, Creteil, France.
RP Martinez, A (reprint author), Hosp Clin Barcelona, Pathol Lab, Hematopathol Sect, Dept Pathol,IDIBAPS, Villarroel 170 E3-P5, E-08036 Barcelona, Spain.
EM antonmar@clinic.ub.es
RI Martinez, Antonio/D-8188-2012; Tomas, Alvaro/L-5531-2015; Song,
Joo/E-5356-2016; Colomo, Luis/A-2259-2016;
OI Martinez, Antonio/0000-0003-0790-9017; Tomas,
Alvaro/0000-0002-7858-2384; Song, Joo/0000-0003-3497-2513; Colomo,
Luis/0000-0001-5236-5085; COLOMER, DOLORS/0000-0001-7486-8484; Rozman,
Maria/0000-0002-2641-1110
FU Instituto de Salud Carlos III, Fondo de Investigacion Sanitaria
[PI080095, PI050458]; Spanish Comision Interministerial de Ciencia y
Tecnologia (CICYT) [SAF08-3630]; Red Tematica de Investigacion
Cooperativa del Cancer (RTICC) [RD06/0020/0039]; Instituto de Salud
Carlos III; Center for Cancer Research, National Cancer Institute
FX Supported by Instituto de Salud Carlos III, Fondo de Investigacion
Sanitaria) PI080095 (AM) and PI050458 (TE). The Spanish Comision
Interministerial de Ciencia y Tecnologia (CICYT) SAF08-3630 (EC), Red
Tematica de Investigacion Cooperativa del Cancer (RTICC) RD06/0020/0039
(EC), AGH is a fellow supported by the Instituto de Salud Carlos III.
This study was also supported by the Intramural Research Program of the
Center for Cancer Research, National Cancer Institute. For the remaining
authors none were declared.
NR 38
TC 43
Z9 43
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0147-5185
J9 AM J SURG PATHOL
JI Am. J. Surg. Pathol.
PD AUG
PY 2011
VL 35
IS 8
BP 1214
EP 1225
DI 10.1097/PAS.0b013e31822067d1
PG 12
WC Pathology; Surgery
SC Pathology; Surgery
GA 792GD
UT WOS:000292728200016
PM 21753698
ER
PT J
AU Chau, M
Forcinito, P
Andrade, AC
Hegde, A
Ahn, S
Lui, JC
Baron, J
Nilsson, O
AF Chau, Michael
Forcinito, Patricia
Andrade, Anenisia C.
Hegde, Anita
Ahn, Sohyun
Lui, Julian C.
Baron, Jeffrey
Nilsson, Ola
TI Organization of the Indian hedgehog - parathyroid hormone-related
protein system in the postnatal growth plate
SO JOURNAL OF MOLECULAR ENDOCRINOLOGY
LA English
DT Article
ID ENDOCHONDRAL BONE-DEVELOPMENT; PTH-RELATED-PROTEIN; CATCH-UP GROWTH;
CHONDROCYTE PROLIFERATION; EPIPHYSEAL FUSION; GENE-EXPRESSION; RESTING
ZONE; DIFFERENTIATION; SENESCENCE; PEPTIDE
AB In embryonic growth cartilage, Indian hedgehog (Ihh) and parathyroid hormone-related protein (PTHrP) participate in a negative feedback loop that regulates chondrocyte differentiation. Postnatally, this region undergoes major structural and functional changes. To explore the organization of the Ihh-PTHrP system in postnatal growth plate, we microdissected growth plates of 7-day-old rats into their constituent zones and assessed expression of genes participating in the Ihh-PTHrP feedback loop. Ihh, Patched 1, Smoothened, Gli1, Gli2, Gli3, and Pthr1 were expressed in regions analogous to the expression domains in embryonic growth cartilage. However, PTHrP was expressed in resting zone cartilage, a site that differs from the embryonic source, the periarticular cells. We then used mice in which lacZ has replaced coding sequences of Gli1 and thus serves as a marker for active hedgehog signaling. At 1, 4, 8, and 12 weeks of age, lacZ expression was detected in a pattern analogous to that of embryonic cartilage. The findings support the hypothesis that the embryonic Ihh-PTHrP feedback loop is maintained in the postnatal growth plate except that the source of PTHrP has shifted to a more proximal location in the resting zone.
C1 [Chau, Michael; Andrade, Anenisia C.; Nilsson, Ola] Karolinska Inst, Ctr Mol Med, Growth & Cartilage Unit, SE-17176 Stockholm, Sweden.
[Chau, Michael; Andrade, Anenisia C.; Nilsson, Ola] Karolinska Inst, Dept Womens & Childrens Hlth, Div Pediat Endocrinol, SE-17176 Stockholm, Sweden.
[Chau, Michael; Andrade, Anenisia C.; Nilsson, Ola] Karolinska Univ Hosp, SE-17176 Stockholm, Sweden.
[Forcinito, Patricia; Hegde, Anita; Lui, Julian C.; Baron, Jeffrey; Nilsson, Ola] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
[Ahn, Sohyun] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Dev Neurogenet, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA.
RP Nilsson, O (reprint author), Karolinska Inst, Ctr Mol Med, Growth & Cartilage Biol Unit, SE-17176 Stockholm, Sweden.
EM ola.nilsson@ki.se
RI Lui, Chun Kin Julian/E-2253-2012;
OI Nilsson, Ola/0000-0002-9986-8138
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, NIH, Bethesda, MD, USA; Swedish Research Council
[K2007-52X-20316-01-4]; Stockholm County Council; Swedish Society of
Medicine; HKH kronprinsessan Lovisas Forening for Barnasjukvard;
Sallskapet Barnavard; Stiftelsen Frimurare Barnhuset i Stockholm;
Karolinska Institutet
FX This research was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, NIH, Bethesda, MD, USA. O N was supported by an ESPE
Research Fellowship Grant and grants from the Swedish Research Council
(K2007-52X-20316-01-4), the Stockholm County Council, the Swedish
Society of Medicine, HKH kronprinsessan Lovisas Forening for
Barnasjukvard, Sallskapet Barnavard, Stiftelsen Frimurare Barnhuset i
Stockholm, and the Karolinska Institutet.
NR 39
TC 17
Z9 21
U1 0
U2 10
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 0952-5041
J9 J MOL ENDOCRINOL
JI J. Mol. Endocrinol.
PD AUG
PY 2011
VL 47
IS 1
BP 99
EP 107
DI 10.1530/JME-10-0177
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 821TK
UT WOS:000294997100013
PM 21642420
ER
PT J
AU Gonzalez, C
Lopez-Rodriguez, A
Srikumar, D
Rosenthal, JJC
Holmgren, M
AF Gonzalez, Carlos
Lopez-Rodriguez, Angelica
Srikumar, Deepa
Rosenthal, Joshua J. C.
Holmgren, Miguel
TI Editing of human K(V)1.1 channel mRNAs disrupts binding of the
N-terminus tip at the intracellular cavity
SO NATURE COMMUNICATIONS
LA English
DT Article
ID SHAKER-K+ CHANNEL; POTASSIUM CHANNELS; INACTIVATION GATE; EYE-MOVEMENT;
BETA-SUBUNIT; RECEPTOR; NEURONS; CELLS; PORE; PROPAGATION
AB In the nervous system, A -> I RNA editing has an important role in regulating neuronal excitability. Ligand-gated membrane receptors, synaptic proteins, as well as ion channels, are targets for recoding by RNA editing. Although scores of editing sites have been identified in the mammalian brain, little is known about the functional alterations that they cause, and even less about the mechanistic underpinnings of how they change protein function. We have previously shown that an RNA editing event (1400 V) alters the inner permeation pathway of human K(V)1.1, modifying the kinetics of fast inactivation. Here we show that the channel's inactivation gate enters deep into the ion permeation pathway and the very tip establishes a direct hydrophobic interaction with the edited position. By converting I to V, the intimacy of the interaction is reduced, allowing the inactivation gate to unbind with much faster kinetics.
C1 [Rosenthal, Joshua J. C.] Univ Puerto Rico, Inst Neurobiol, San Juan, PR 00901 USA.
[Gonzalez, Carlos] Univ Valparaiso, Ctr Interdisciplinario Neurociencia Valparaiso, Valparaiso 2340000, Chile.
[Lopez-Rodriguez, Angelica; Srikumar, Deepa; Holmgren, Miguel] Natl Inst Neurol Disorders & Stroke, Mol Neurophysiol Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
[Rosenthal, Joshua J. C.] Univ Puerto Rico, Dept Biochem, San Juan, PR 00936 USA.
RP Rosenthal, JJC (reprint author), Univ Puerto Rico, Inst Neurobiol, Med Sci Campus, San Juan, PR 00901 USA.
EM Joshua.rosenthal@upr.edu; holmgren@ninds.nih.gov
FU National Institutes of Health (NIH) [1 R01 NS064259]; NINDS; NSF
[IBN-0344070]
FX We thank the DNA sequencing facility at the National Institute of
Neurological Disorders and Stroke (NINDS) for sequencing all DNA
constructs used in this study, and the Section on Instrumentation of the
National Institute of Mental Health for technical assistance. We also
thank the Imaging Facility at NINDS for training and support in the use
of the confocal microscope. This research was directly supported by the
Intramural Research Program of the National Institutes of Health, NINDS,
and from grants NSF IBN-0344070 and NIH 1 R01 NS064259 to J.J.C.R.
NR 50
TC 18
Z9 18
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD AUG
PY 2011
VL 2
AR 436
DI 10.1038/ncomms1446
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 819DV
UT WOS:000294806500029
PM 21847110
ER
PT J
AU Freedman, AN
Yu, BB
Gail, MH
Costantino, JP
Graubard, BI
Vogel, VG
Anderson, GL
McCaskill-Stevens, W
AF Freedman, Andrew N.
Yu, Binbing
Gail, Mitchell H.
Costantino, Joseph P.
Graubard, Barry I.
Vogel, Victor G.
Anderson, Garnet L.
McCaskill-Stevens, Worta
TI Development of a Benefit/Risk Assessment Tool for Breast Cancer
Chemoprevention
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Meeting Abstract
C1 [Freedman, Andrew N.; Gail, Mitchell H.; Graubard, Barry I.; McCaskill-Stevens, Worta] NCI, Bethesda, MD 20892 USA.
[Yu, Binbing] NIA, Bethesda, MD 20892 USA.
[Costantino, Joseph P.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA.
[Vogel, Victor G.] Geisinger Hlth Syst, Danville, PA USA.
[Anderson, Garnet L.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1053-8569
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD AUG
PY 2011
VL 20
SU 1
MA 627
BP S273
EP S274
PG 2
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA 821AG
UT WOS:000294946600605
ER
PT J
AU Freedman, AN
van der Zee, AHM
Zineh, I
Pacanowski, M
Papaluca-Amati, M
Carl, K
Leufkens, B
AF Freedman, Andrew N.
van der Zee, Anke-Hilse Maitland
Zineh, Issam
Pacanowski, Michael
Papaluca-Amati, Marissa
Carl, Kevin
Leufkens, Burt
TI Regulatory Trends in Pharmacogenomic Biomarker Evaluation (Molecular
Epi/Biomarkers/Pharmacogenetics SIG Symposium)
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Meeting Abstract
C1 [Freedman, Andrew N.] NCI, Bethesda, MD 20892 USA.
[van der Zee, Anke-Hilse Maitland; Leufkens, Burt] Univ Utrecht, Utrecht, Netherlands.
[Zineh, Issam; Pacanowski, Michael] US FDA, Silver Spring, MD USA.
EMA, London, England.
Novartis, Suffern, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1053-8569
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD AUG
PY 2011
VL 20
SU 1
MA 42
BP S19
EP S19
PG 1
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA 821AG
UT WOS:000294946600043
ER
PT J
AU Lund, JL
Sanoff, HK
Sturmer, T
Sandler, RS
Brookhart, AM
Warren, JL
Harlan, LC
AF Lund, Jennifer L.
Sanoff, Hanna K.
Sturmer, Til
Sandler, Robert S.
Brookhart, Alan M.
Warren, Joan L.
Harlan, Linda C.
TI Patterns of On- and Off-Label Oxaliplatin Use among Stage II and III
Colorectal Cancer Patients in 2005
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Meeting Abstract
C1 [Lund, Jennifer L.; Sturmer, Til; Brookhart, Alan M.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Sanoff, Hanna K.] Univ Virginia, Dept Hematol Oncol, Charlottesville, VA USA.
[Sandler, Robert S.] Univ N Carolina, Div Gastroenterol & Hepatol, Chapel Hill, NC USA.
[Warren, Joan L.; Harlan, Linda C.] NCI, Appl Res Program, Hlth Serv & Econ Branch, Bethesda, MD 20892 USA.
RI Lund, Jennifer/G-9420-2012
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1053-8569
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD AUG
PY 2011
VL 20
SU 1
MA 269
BP S116
EP S117
PG 2
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA 821AG
UT WOS:000294946600259
ER
PT J
AU Tilson, H
Roberts, SS
Watts, DH
Beckerman, K
Dominguez, K
Pikis, A
Scaglia, F
Baugh, B
Haddad, W
Peng, M
Trylesinski, A
AF Tilson, Hugh
Roberts, Susan S.
Watts, D. Heather
Beckerman, Karen
Dominguez, Kenneth
Pikis, Andreas
Scaglia, Fernando
Baugh, Bryan
Haddad, William
Peng, Michael
Trylesinski, Aldo
TI The Antiretroviral Pregnancy Registry: A 20(th) Anniversary Celebration
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Meeting Abstract
C1 [Tilson, Hugh] Univ N Carolina, UNC Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Roberts, Susan S.] Univ N Carolina, Clin Res Program, Wilmington, NC 28401 USA.
[Roberts, Susan S.] Kendle Int Inc, Registries & Hlth Outcomes, Wilmington, NC USA.
[Watts, D. Heather] NICHD, PAMA, CRMC, NIH, Bethesda, MD USA.
[Beckerman, Karen] Albert Einstein Coll Med, New Rochelle, NY USA.
[Dominguez, Kenneth] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Pikis, Andreas] US FDA, Div Antiviral Drugs & Prod, Silver Spring, MD USA.
[Scaglia, Fernando] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Baugh, Bryan] Tibotec Therapeut, Clin Affairs, Titusville, NJ USA.
[Haddad, William] Biogenerics Inc, Poughquag, NY USA.
[Peng, Michael] Roche, Roche Biometr EpiPRO, Nutley, NJ USA.
[Trylesinski, Aldo] Novartis Pharma AG, Immunol & Infect Dis, Basel, Switzerland.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY PERIODICALS, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA
SN 1053-8569
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD AUG
PY 2011
VL 20
SU 1
MA 437
BP S190
EP S191
PG 2
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA 821AG
UT WOS:000294946600422
ER
PT J
AU Tsai, HT
Smith, SW
Warren, JL
Freedman, AN
Sansbury, LB
Marshall, JL
Potosky, AL
AF Tsai, Huei-Ting
Smith, Sheila Weiss
Warren, Joan L.
Freedman, Andrew N.
Sansbury, Leah B.
Marshall, John L.
Potosky, Arnold L.
TI Risks of Congestive Heart Failure and Cardiomyopathy Associated with
Bevacizumab Use in Colorectal Cancer Chemotherapy Patients: A
Population-Based Study
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Meeting Abstract
C1 [Tsai, Huei-Ting; Marshall, John L.; Potosky, Arnold L.] Georgetown Univ, Med Ctr, Washington, DC 20007 USA.
[Smith, Sheila Weiss] Univ Maryland, Sch Pharm, Ctr Drug Safety, Baltimore, MD 21201 USA.
[Warren, Joan L.; Freedman, Andrew N.; Sansbury, Leah B.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1053-8569
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD AUG
PY 2011
VL 20
SU 1
MA 281
BP S121
EP S122
PG 2
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA 821AG
UT WOS:000294946600271
ER
PT J
AU Brzezinski, K
Baj, A
Walejko, P
Witkowski, S
Dauter, Z
AF Brzezinski, Krzysztof
Baj, Aneta
Walejko, Piotr
Witkowski, Stanislaw
Dauter, Zbigniew
TI 6-Hydroxy-2,5,7,8-tetramethyl-3,4-dihydro-2H-1-benzopyran-2-carbonitrile
, from synchrotron data
SO ACTA CRYSTALLOGRAPHICA SECTION E-STRUCTURE REPORTS ONLINE
LA English
DT Article
AB The crystal structure of the title compound, C14H17NO2, solved and refined against synchrotron diffraction data, contains one formula unit in an asymmetric unit. In the crystal, molecules form right-handed helices located at the 2(1) screw axis parallel to the a-axis direction, generated by O-H center dot center dot center dot N hydrogen bonding between the hydroxy group and carbonitrile group of an adjacent molecule.
C1 [Brzezinski, Krzysztof; Dauter, Zbigniew] NCI, Synchrotron Radiat Res Sect, MCL, Argonne Natl Lab,Biosci Div, Argonne, IL 60439 USA.
[Baj, Aneta; Walejko, Piotr; Witkowski, Stanislaw] Univ Bialystok, Inst Chem, PL-15443 Bialystok, Poland.
RP Brzezinski, K (reprint author), NCI, Synchrotron Radiat Res Sect, MCL, Argonne Natl Lab,Biosci Div, Bldg 202, Argonne, IL 60439 USA.
EM kbrzezinski@anl.gov
FU NIH, National Cancer Institute, Center for Cancer Research; US
Department of Energy [W-31-109-Eng-38]
FX This work was supported in part by the Intramural Research Program of
the NIH, National Cancer Institute, Center for Cancer Research. X-ray
data were collected at Southeast Regional Collaborative Access Team
(SER-CAT) 22-ID beamline at the Advanced Photon Source, Argonne National
Laboratory. Use of the APS was supported by the US Department of Energy
under contract No. W-31-109-Eng-38.
NR 9
TC 1
Z9 1
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-5368
J9 ACTA CRYSTALLOGR E
JI Acta Crystallogr. Sect. E.-Struct Rep. Online
PD AUG
PY 2011
VL 67
BP O1901
EP U1787
DI 10.1107/S1600536811025517
PN 8
PG 13
WC Crystallography
SC Crystallography
GA 816PF
UT WOS:000294613900146
PM 22090952
ER
PT J
AU Wroblewski, K
Sen, HN
Yeh, S
Faia, L
Li, ZG
Sran, P
Gangaputra, S
Vitale, S
Sherry, P
Nussenblatt, R
AF Wroblewski, Keith
Sen, H. Nida
Yeh, Steven
Faia, Lisa
Li, Zhuging
Sran, Pushpa
Gangaputra, Sapna
Vitale, Susan
Sherry, Patti
Nussenblatt, Robert
TI Long-term daclizumab therapy for the treatment of noninfectious ocular
inflammatory disease
SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE
LA English
DT Article
ID WEGENERS-GRANULOMATOSIS; AUTOIMMUNE-DISEASES; UVEITIS; MALIGNANCIES;
RITUXIMAB; SAFETY; AGENTS; TRIAL; RISK
AB Objective: Safety and efficacy of daclizumab during an 11-year period.
Design: Structured, retrospective chart review.
Participants: Thirty-nine patients.
Methods: Patients with chronic, noninfectious intermediate and/or posterior uveitis.
Results: Thirty-nine patients (78 eyes) were treated for a mean of 40.3 months. Visual acuity improved by 2 lines in the better eye in 7 patients (18.4%) and worsened by 2 lines in 6 patients (15.8%) with a mean of 2.8 Snellen lines of vision lost per eye. Six eyes with vitreous cell less than grade 2 lost 2 lines of vision and 7 eyes with less than grade 2 vitreous cell improved 2 lines. Mean number of immunosuppressive medications per patient decreased from 1.89 medications/patient to 1.17 medications/patient. The average number of periocular injections per patient was 1.46 (range, 0-9). The mean number of flares was 2.05/patient (range, 0-12), with the rate being 0.62 flares per patient-year. Four patients developed cancer during the course of this study. Mean time to onset of malignancy was 26 months and the mean age in this group was 49 years.
Conclusions: Daclizumab demonstrated efficacy in the reduction of concomitant immunosuppressive medication, stabilization of visual acuity, and the prevention of uveitic flares in most cases. Dermatologic complications were the most frequently observed adverse event in our series. Four patients developed solid tumor malignancies during this 11-year period.
C1 [Wroblewski, Keith] Walter Reed Army Med Ctr, Ophthalmol Serv, Washington, DC 20307 USA.
[Wroblewski, Keith; Sen, H. Nida; Yeh, Steven; Faia, Lisa; Li, Zhuging; Sran, Pushpa; Gangaputra, Sapna; Vitale, Susan; Sherry, Patti; Nussenblatt, Robert] NIH, Immunol Lab, Bethesda, MD 20892 USA.
RP Wroblewski, K (reprint author), Walter Reed Army Med Ctr, Ophthalmol Serv, Washington, DC 20307 USA.
EM keith.wroblewski@amedd.army.mil
FU Heed Ophthalmic Fellowship Grant
FX Dr. Yeh received a Heed Ophthalmic Fellowship Grant for research.
NR 25
TC 11
Z9 12
U1 0
U2 1
PU CANADIAN OPHTHAL SOC
PI OTTAWA
PA 1525 CARLING AVE SUITE 610, OTTAWA, ONTARIO K1Z 8R9, CANADA
SN 0008-4182
J9 CAN J OPHTHALMOL
JI Can. J. Opthalmol.-J. Can. Opthalmol.
PD AUG
PY 2011
VL 46
IS 4
BP 322
EP 328
DI 10.1016/j.jcjo.2011.06.008
PG 7
WC Ophthalmology
SC Ophthalmology
GA 819AS
UT WOS:000294798400007
PM 21816251
ER
PT J
AU Gonzalez, F
Patterson, A
Krauz, K
Idle, J
AF Gonzalez, Frank
Patterson, Andrew
Krauz, Kristopher
Idle, Jeffrey
TI Investigating the roles of lipids in disease and chemical toxicities
using metabolomics
SO CHEMISTRY AND PHYSICS OF LIPIDS
LA English
DT Meeting Abstract
CT 52nd International Conference on the Bioscience of Lipids - Expanding
the Horizons of Lipidomics
CY AUG 30-SEP 03, 2011
CL Univ Warsaw, Old Library, Warsaw, POLAND
SP Journal Biol Chem/Herbert Tabor Young Investigator Award, Bio-Rad Labs, Polish Minist Sci & Higher Educ, Polish Biochem Soc, Visegrad Fund, Johnson & Johnson, CPPW, Avanti Polar Lipids, Inc, Elsevier, Perlan Technol Polska, Cayman Chem, Olympus Polska, Sigma Life Sci, Bruker, Larodan Fine Chem, Sympatec GmbH
HO Univ Warsaw, Old Library
C1 [Gonzalez, Frank; Patterson, Andrew; Krauz, Kristopher] NCI, NIH, Bethesda, MD 20892 USA.
[Idle, Jeffrey] Univ Bern, Dept Clin Res, Bern, Switzerland.
NR 0
TC 0
Z9 0
U1 1
U2 4
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0009-3084
J9 CHEM PHYS LIPIDS
JI Chem. Phys. Lipids
PD AUG
PY 2011
VL 164
SU S
BP S5
EP S5
DI 10.1016/j.chemphyslip.2011.05.041
PG 1
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 818JL
UT WOS:000294747900012
ER
PT J
AU MacRae, CA
Vasan, RS
AF MacRae, Calum A.
Vasan, Ramachandran S.
TI Next-Generation Genome-Wide Association Studies Time to Focus on
Phenotype?
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Editorial Material
DE Editorials; cardiomyopathy; genetics; genome-wide association studies
ID MISSING HERITABILITY; ATRIAL-FIBRILLATION; COMPLEX DISEASES; PHENOME
PROJECT; SCHIZOPHRENIA; VARIANT; RISK
C1 [MacRae, Calum A.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[MacRae, Calum A.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Vasan, Ramachandran S.] NHLBI, Boston, MA USA.
RP MacRae, CA (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
EM cmacrae@partners.org
OI Ramachandran, Vasan/0000-0001-7357-5970
FU NHLBI NIH HHS [HL098938, N01-HC 25195, N01HC25195, R21 HL098938, R21
HL098938-01, R21 HL098938-02]
NR 32
TC 13
Z9 13
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1942-325X
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD AUG
PY 2011
VL 4
IS 4
BP 334
EP 336
DI 10.1161/CIRCGENETICS.111.960765
PG 3
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA 807MB
UT WOS:000293901300003
PM 21846867
ER
PT J
AU Zhao, Q
Gu, DF
Hixson, JE
Liu, DP
Rao, DC
Jaquish, CE
Kelly, TN
Lu, FH
Ma, JX
Mu, JJ
Shimmin, LC
Chen, JC
Mei, H
Hamm, LL
He, J
AF Zhao, Qi
Gu, Dongfeng
Hixson, James E.
Liu, De-Pei
Rao, Dabeeru C.
Jaquish, Cashell E.
Kelly, Tanika N.
Lu, Fanghong
Ma, Jixiang
Mu, Jianjun
Shimmin, Lawrence C.
Chen, Jichun
Mei, Hao
Hamm, L. Lee
He, Jiang
TI Common Variants in Epithelial Sodium Channel Genes Contribute to Salt
Sensitivity of Blood Pressure The GenSalt Study
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Article
DE blood pressure; epithelial sodium channel; genetic variant; salt
sensitivity
ID SUBUNIT PROMOTER VARIANT; BETA-SUBUNIT; ESSENTIAL-HYPERTENSION;
LIDDLES-SYNDROME; GAMMA-SUBUNIT; MISSENSE MUTATION; T594M MUTATION;
DIETARY-SODIUM; ENAC GENE; ASSOCIATION
AB Background-Rare mutations of the epithelial sodium channel (ENaC) lead to mendelian forms of salt-sensitive hypertension or salt-wasting hypotension. We aimed to examine the association between common variants in the ENaC genes and salt sensitivity of blood pressure (BP).
Methods and Results-A total of 1906 Han Chinese participated in the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) study, which includes a 7-day low-sodium intake (51.3 mmol sodium/d) followed by a 7-day high-sodium intake (307.8 mmol sodium/d). Nine BP measurements were obtained at baseline and each intervention period using a random-zero sphygmomanometer. Single-nucleotide polymorphisms, both tagging and functional, from the 3 ENaC subunits, alpha, beta, and gamma (SCNN1A, SCNN1B, and SCNN1G), were genotyped. Multiple common single-nucleotide polymorphisms in SCNN1G were significantly associated with BP response to low-sodium intervention (rs4073930, P = 1.7 x 10(-5); rs4073291, P = 1.1 x 10(-5); rs7404408, P = 1.9 x 10(-5); rs5735, P = 3.0 x 10(-4); rs4299163, P = 0.004; and rs4499238, P = 0.002) even after correcting for multiple testing. For example, under an additive model, the minor allele G of SNP rs4073291 was associated with 1.33 mm Hg lower systolic BP reduction during low-sodium intervention.
Conclusions-This large dietary sodium intervention study indicates that common variants of ENaC subunits may contribute to the variation of BP response to dietary sodium intake. Future studies are warranted to confirm these findings in an independent population and to identify functional variants for salt sensitivity.
C1 [Zhao, Qi; Kelly, Tanika N.; Mei, Hao; He, Jiang] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA 70112 USA.
[Hamm, L. Lee; He, Jiang] Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70112 USA.
[Gu, Dongfeng; Chen, Jichun] Chinese Acad Med Sci, Cardiovasc Inst, Div Populat Genet & Prevent, Beijing 100037, Peoples R China.
[Gu, Dongfeng; Chen, Jichun] Chinese Acad Med Sci, Fuwai Hosp, Beijing 100037, Peoples R China.
[Gu, Dongfeng; Liu, De-Pei; Chen, Jichun] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Gu, Dongfeng; Chen, Jichun] Natl Ctr Cardiovasc Dis, Beijing, Peoples R China.
[Hixson, James E.; Shimmin, Lawrence C.] Univ Texas Sch Publ Hlth, Ctr Human Genet, Houston, TX USA.
[Liu, De-Pei] Chinese Acad Med Sci, Natl Lab Med Mol Biol, Inst Basic Med Sci, Beijing 100037, Peoples R China.
[Rao, Dabeeru C.] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA.
[Jaquish, Cashell E.] NHLBI, Div Cardiovasc Dis Sci, Bethesda, MD 20892 USA.
[Lu, Fanghong] Shandong Acad Med Sci, Tsinan, Shandong, Peoples R China.
[Ma, Jixiang; Mu, Jianjun] Shandong Ctr Dis Control & Prevent, Tsinan, Shandong, Peoples R China.
[Ma, Jixiang; Mu, Jianjun] Xi An Jiao Tong Univ, Sch Med, Dept Med, Xian, Shaanxi, Peoples R China.
RP Gu, DF (reprint author), Chinese Acad Med Sci, Cardiovasc Inst, Div Populat Genet & Prevent, 167 Beilishi Rd, Beijing 100037, Peoples R China.
EM gudongfeng@vip.sina.com; jhe@tulane.edu
FU National Heart, Lung, and Blood Institute, National Institutes of
Health, Bethesda, MD [U01HL072507, R01HL087263, R01HL090682]
FX The Genetic Epidemiology Network of Salt Sensitivity (GenSalt) is
supported by research grants (U01HL072507, R01HL087263, and R01HL090682)
from the National Heart, Lung, and Blood Institute, National Institutes
of Health, Bethesda, MD.
NR 45
TC 28
Z9 37
U1 1
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1942-325X
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD AUG
PY 2011
VL 4
IS 4
BP 375
EP U85
DI 10.1161/CIRCGENETICS.110.958629
PG 12
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA 807MB
UT WOS:000293901300010
PM 21562341
ER
PT J
AU Wild, PS
Zeller, T
Schillert, A
Szymczak, S
Sinning, CR
Deiseroth, A
Schnabel, RB
Lubos, E
Keller, T
Eleftheriadis, MS
Bickel, C
Rupprecht, HJ
Wilde, S
Rossmann, H
Diemert, P
Cupples, LA
Perret, C
Erdmann, J
Stark, K
Kleber, ME
Epstein, SE
Voight, BF
Kuulasmaa, K
Li, MY
Schafer, AS
Klopp, N
Braund, PS
Sager, H
Demissie, S
Proust, C
Konig, IR
Wichmann, HE
Reinhard, W
Hoffmann, MM
Virtamo, J
Burnett, MS
Siscovick, D
Wiklund, PG
Qu, LM
El Mokthari, NE
Thompson, JR
Peters, A
Smith, AV
Yon, E
Baumert, J
Hengstenberg, C
Marz, W
Amouyel, P
Devaney, J
Schwartz, S
Saarela, O
Mehta, NN
Rubin, D
Silander, K
Hall, AS
Ferriers, J
Harris, TB
Melander, O
Kee, F
Hakonarson, H
Schrezenmeir, J
Gudnason, V
Elosua, R
Arveiler, D
Evans, A
Rader, DJ
Illig, T
Schreiber, S
Bis, JC
Altshuler, D
Kavousi, M
Witteman, JCM
Uitterlinden, AG
Hofman, A
Folsom, AR
Barbalic, M
Boerwinkle, E
Kathiresan, S
Reilly, MP
O'Donnell, CJ
Samani, NJ
Schunkert, H
Cambien, F
Lackner, KJ
Tiret, L
Salomaa, V
Munzel, T
Ziegler, A
Blankenberg, S
AF Wild, Philipp S.
Zeller, Tanja
Schillert, Arne
Szymczak, Silke
Sinning, Christoph R.
Deiseroth, Arne
Schnabel, Renate B.
Lubos, Edith
Keller, Till
Eleftheriadis, Medea S.
Bickel, Christoph
Rupprecht, Hans J.
Wilde, Sandra
Rossmann, Heidi
Diemert, Patrick
Cupples, L. Adrienne
Perret, Claire
Erdmann, Jeanette
Stark, Klaus
Kleber, Marcus E.
Epstein, Stephen E.
Voight, Benjamin F.
Kuulasmaa, Kari
Li, Mingyao
Schaefer, Arne S.
Klopp, Norman
Braund, Peter S.
Sager, Hendrik
Demissie, Serkalem
Proust, Carole
Koenig, Inke R.
Wichmann, Heinz-Erich
Reinhard, Wibke
Hoffmann, Michael M.
Virtamo, Jarmo
Burnett, Mary Susan
Siscovick, David
Wiklund, Per Gunnar
Qu, Liming
El Mokthari, Nour Eddine
Thompson, John R.
Peters, Annette
Smith, Albert V.
Yon, Emmanuelle
Baumert, Jens
Hengstenberg, Christian
Maerz, Winfried
Amouyel, Philippe
Devaney, Joseph
Schwartz, Stephen
Saarela, Olli
Mehta, Nehal N.
Rubin, Diana
Silander, Kaisa
Hall, Alistair S.
Ferriers, Jean
Harris, Tamara B.
Melander, Olle
Kee, Frank
Hakonarson, Hakon
Schrezenmeir, Juergen
Gudnason, Vilmundur
Elosua, Roberto
Arveiler, Dominique
Evans, Alun
Rader, Daniel J.
Illig, Thomas
Schreiber, Stefan
Bis, Joshua C.
Altshuler, David
Kavousi, Maryam
Witteman, Jaqueline C. M.
Uitterlinden, Andre G.
Hofman, Albert
Folsom, Aaron R.
Barbalic, Maja
Boerwinkle, Eric
Kathiresan, Sekar
Reilly, Muredach P.
O'Donnell, Christopher J.
Samani, Nilesh J.
Schunkert, Heribert
Cambien, Francois
Lackner, Karl J.
Tiret, Laurence
Salomaa, Veikko
Munzel, Thomas
Ziegler, Andreas
Blankenberg, Stefan
TI A Genome-Wide Association Study Identifies LIPA as a Susceptibility Gene
for Coronary Artery Disease
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Article
DE coronary artery disease; genome-wide association studies; gene
expression; genetic variation; genomics; eQTL; eSNP; LIPA
ID LYSOSOMAL ACID LIPASE; LOW-DENSITY-LIPOPROTEIN; MYOCARDIAL-INFARCTION;
WOLMAN-DISEASE; HEART-DISEASE; EXPRESSION; RISK; COHORTS;
ATHEROSCLEROSIS; CHOLESTEROL
AB Background-eQTL analyses are important to improve the understanding of genetic association results. We performed a genome-wide association and global gene expression study to identify functionally relevant variants affecting the risk of coronary artery disease (CAD).
Methods and Results-In a genome-wide association analysis of 2078 CAD cases and 2953 control subjects, we identified 950 single-nucleotide polymorphisms (SNPs) that were associated with CAD at P<10(-3). Subsequent in silico and wet-laboratory replication stages and a final meta-analysis of 21 428 CAD cases and 38 361 control subjects revealed a novel association signal at chromosome 10q23.31 within the LIPA (lysosomal acid lipase A) gene (P=3.7 x 10(-8); odds ratio, 1.1; 95% confidence interval, 1.07 to 1.14). The association of this locus with global gene expression was assessed by genome-wide expression analyses in the monocyte transcriptome of 1494 individuals. The results showed a strong association of this locus with expression of the LIPA transcript (P=1.3 x 10(-96)). An assessment of LIPA SNPs and transcript with cardiovascular phenotypes revealed an association of LIPA transcript levels with impaired endothelial function (P=4.4 x 10(-3)).
Conclusions-The use of data on genetic variants and the addition of data on global monocytic gene expression led to the identification of the novel functional CAD susceptibility locus LIPA, located on chromosome 10q23.31. The respective eSNPs associated with CAD strongly affect LIPA gene expression level, which was related to endothelial dysfunction, a precursor of CAD. (Circ Cardiovasc Genet. 2011;4:403-412.)
C1 [Wild, Philipp S.; Zeller, Tanja; Sinning, Christoph R.; Deiseroth, Arne; Schnabel, Renate B.; Lubos, Edith; Keller, Till; Eleftheriadis, Medea S.; Rupprecht, Hans J.; Wilde, Sandra; Munzel, Thomas; Blankenberg, Stefan] Univ Med Ctr Mainz, Dept Med 2, D-55131 Mainz, Germany.
[Schillert, Arne; Szymczak, Silke; Koenig, Inke R.; Ziegler, Andreas] Univ Lubeck, Univ Hosp Schleswig Holstein, Inst Med Biometry & Stat, D-23562 Lubeck, Germany.
[Bickel, Christoph] Fed Armed Hosp Koblenz, Dept Internal Med, D-56072 Koblenz, Germany.
[Rossmann, Heidi; Lackner, Karl J.] Univ Med Ctr Mainz, Inst Clin Chem & Lab Med, D-55131 Mainz, Germany.
[Diemert, Patrick; Erdmann, Jeanette; Sager, Hendrik; Schunkert, Heribert] Univ Lubeck, Med Klin 2, D-23538 Lubeck, Germany.
[Cupples, L. Adrienne; Demissie, Serkalem; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Perret, Claire; Proust, Carole; Yon, Emmanuelle; Cambien, Francois; Tiret, Laurence] Univ Paris 06, INSERM, UMRS937, Paris, France.
[Stark, Klaus; Reinhard, Wibke; Hengstenberg, Christian] Univ Hosp Regensburg, Klin & Poliklin Innere Med 2, D-93053 Regensburg, Germany.
[Kleber, Marcus E.] LURIC Study Nonprofit LLC, D-79098 Freiburg, Germany.
[Epstein, Stephen E.; Burnett, Mary Susan; Devaney, Joseph] MedStar Hlth Res Inst, Cardiovasc Res Inst, Washington, DC 20010 USA.
[Voight, Benjamin F.] Broad Inst, Cambridge Ctr 5, Cambridge, MA 02142 USA.
[Kuulasmaa, Kari; Virtamo, Jarmo; Saarela, Olli; Silander, Kaisa; Salomaa, Veikko] Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland.
[Li, Mingyao; Qu, Liming] Univ Penn, Dept Biostat, Philadelphia, PA 19104 USA.
[Schaefer, Arne S.; Schreiber, Stefan] Univ Kiel, Inst Clin Mol Biol, D-24105 Kiel, Germany.
[Klopp, Norman; Wichmann, Heinz-Erich; Peters, Annette; Baumert, Jens; Illig, Thomas] Helmholtz Zentrum Munchen, Inst Epidemiol, D-85764 Neuherberg, Germany.
[Braund, Peter S.; Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England.
[Braund, Peter S.; Samani, Nilesh J.] Glenfield Hosp, Leicester NIHR Biomed Res Unit Cardiovasc Dis, Leicester LE3 9QP, Leics, England.
[Hoffmann, Michael M.] Univ Med Ctr, Div Clin Chem, Dept Med, D-79075 Freiburg, Germany.
[Siscovick, David; Schwartz, Stephen] Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98101 USA.
[Siscovick, David; Schwartz, Stephen] Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98101 USA.
[Wiklund, Per Gunnar] Umea Univ, Dept Publ Hlth & Clin Med, SE-90185 Umea, Sweden.
[El Mokthari, Nour Eddine] Univ Med Ctr Schleswig Holstein, Clin Cardiol, D-24105 Kiel, Germany.
[Thompson, John R.] Univ Leicester, Dept Hlth Sci, Leicester LE1 7RH, Leics, England.
[Smith, Albert V.; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Smith, Albert V.; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
[Maerz, Winfried] Synlab Ctr Lab Diagnost, D-69037 Heidelberg, Germany.
[Amouyel, Philippe] Pasteur Inst Lille, INSERM, Dept Epidemiol & Publ Hlth, U508, F-59019 Lille, France.
[Mehta, Nehal N.; Reilly, Muredach P.] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Hall, Alistair S.] Univ Leeds, Leeds Inst Genet Hlth & Therapeut, Leeds LS1 3EX, W Yorkshire, England.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Melander, Olle] Lund Univ, Dept Clin Sci, SE-20502 Lund, Sweden.
[Kee, Frank; Evans, Alun] Queens Univ Belfast, UK Clin Res Collaborat Ctr Excellence Publ Hlth, Belfast BT12 6BJ, Antrim, North Ireland.
[Hakonarson, Hakon] Univ Penn, Ctr Appl Genom, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Schrezenmeir, Juergen] Max Rubner Inst, Inst Physiol & Biochem Nutr, D-24103 Kiel, Germany.
[Elosua, Roberto] IMIM Doctor Aiguader, Grp Epidemiol & Genet Cardiovasc, Barcelona 08003, Spain.
[Arveiler, Dominique] Univ Strasbourg, Lab Epidemiol & Sante Publ, F-67085 Strasbourg, France.
[Ferriers, Jean] Fac Med Toulouse, Dept Epidemiol, F-31073 Toulouse, France.
[Rader, Daniel J.] Univ Penn, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA.
[Altshuler, David; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Kavousi, Maryam; Witteman, Jaqueline C. M.; Uitterlinden, Andre G.; Hofman, Albert] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Barbalic, Maja; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA.
[Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Perret, Claire; Proust, Carole; Yon, Emmanuelle; Cambien, Francois; Tiret, Laurence] Sch Med, Paris, France.
RP Blankenberg, S (reprint author), Univ Klinikum Hamburg Eppendorf, Univ Herzzentrum Hamburg, Martinistr 52, D-20246 Hamburg, Germany.
EM s.blankenberg@uke.de
RI Stark, Klaus/D-3813-2009; Szymczak, Silke/C-6625-2013; Altshuler,
David/A-4476-2009; Schreiber, Stefan/B-6748-2008; Schnabel,
Renate/F-6527-2014; Peters, Annette/A-6117-2011; Hoffmann,
Michael/D-4074-2015; Gudnason, Vilmundur/K-6885-2015; Smith,
Albert/K-5150-2015; Konig, Inke/A-4544-2009; Erdmann,
Jeanette/A-4417-2009; Erdmann, Jeanette/P-7513-2014;
OI Stark, Klaus/0000-0002-7832-1942; Altshuler, David/0000-0002-7250-4107;
Schreiber, Stefan/0000-0003-2254-7771; Hoffmann,
Michael/0000-0001-8459-6080; Gudnason, Vilmundur/0000-0001-5696-0084;
Smith, Albert/0000-0003-1942-5845; Cupples, L.
Adrienne/0000-0003-0273-7965; ELOSUA, ROBERTO/0000-0001-8235-0095;
Erdmann, Jeanette/0000-0002-4486-6231; Keller, Till/0000-0002-0895-6491;
Ziegler, Andreas/0000-0002-8386-5397; Kuulasmaa,
Kari/0000-0003-2165-1411; Kleber, Marcus/0000-0003-0663-7275
FU government of Rheinland-Pfalz ("Stiftung Rheinland Pfalz fur
Innovation,") [AZ 961-386261/733]; Johannes Gutenberg-University of
Mainz; National Genome Network [A3 01GS0833, 01GS0831]; Federal Ministry
of Education and Research, Germany; GlaxoSmithKline through an Alternate
Drug Discovery Initiative
FX The Gutenberg Heart Study is funded through the government of
Rheinland-Pfalz ("Stiftung Rheinland Pfalz fur Innovation," contract No.
AZ 961-386261/733), the research programs "Wissen schafft Zukunft" and
"Schwerpunkt Vaskulare Pravention" of the Johannes Gutenberg-University
of Mainz, and its contract with Boehringer Ingelheim and PHILIPS Medical
Systems, including an unrestricted grant for the Gutenberg Heart Study.
Specifically, the research reported in this article was supported by the
National Genome Network "NGFNplus" (contract No. project A3 01GS0833 and
01GS0831) by the Federal Ministry of Education and Research, Germany.;
Drs Reilly and Rader were supported by GlaxoSmithKline through an
Alternate Drug Discovery Initiative research alliance award.
NR 48
TC 57
Z9 60
U1 0
U2 17
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1942-325X
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD AUG
PY 2011
VL 4
IS 4
BP 403
EP U203
DI 10.1161/CIRCGENETICS.110.958728
PG 85
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA 807MB
UT WOS:000293901300014
PM 21606135
ER
PT J
AU Goldstein, DS
AF Goldstein, David S.
TI Patients as a Scientific Resource: Comments on Receiving the Ahrens
Award
SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE
LA English
DT Editorial Material
ID CENTRAL DOPAMINE DEFICIENCY; DISEASE
C1 Natl Inst Neurol Disorders & Stroke, Clin Neurocardiol Sect, Clin Neurosci Program, Div Intramural Res,NIH, Bethesda, MD USA.
RP Goldstein, DS (reprint author), Natl Inst Neurol Disorders & Stroke, Clin Neurocardiol Sect, Clin Neurosci Program, Div Intramural Res,NIH, Bethesda, MD USA.
EM goldsteind@ninds.nih.gov
FU Intramural NIH HHS [Z99 NS999999]
NR 4
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1752-8054
J9 CTS-CLIN TRANSL SCI
JI CTS-Clin. Transl. Sci.
PD AUG
PY 2011
VL 4
IS 4
BP 231
EP 232
DI 10.1111/j.1752-8062.2011.00311.x
PG 2
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 815YQ
UT WOS:000294566300006
PM 21884507
ER
PT J
AU Toulmay, A
Prinz, WA
AF Toulmay, Alexandre
Prinz, William A.
TI Lipid transfer and signaling at organelle contact sites: the tip of the
iceberg
SO CURRENT OPINION IN CELL BIOLOGY
LA English
DT Article
AB Membrane contact sites (MCSs) are formed by the close apposition of membranes of two organelles. They are zones where signals and small molecules, such as lipids and calcium, are exchanged between intracellular compartments. The past few years have seen considerable progress in our understanding of how MCSs form and facilitate the exchange of lipids and signals. Here we summarize what has been learned about MCSs between the endoplamic reticulum (ER) and the plasma membrane, the ER and mitochondria, and the ER and endosomes or lysosomes. These findings suggest that we are just beginning to understand how MCSs form and function.
C1 [Toulmay, Alexandre; Prinz, William A.] NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA.
RP Prinz, WA (reprint author), NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA.
EM wprinz@helix.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases
FX This work was supported by the Intramural Research Fund of the National
Institute of Diabetes and Digestive and Kidney Diseases.
NR 54
TC 96
Z9 97
U1 0
U2 12
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0955-0674
J9 CURR OPIN CELL BIOL
JI Curr. Opin. Cell Biol.
PD AUG
PY 2011
VL 23
IS 4
BP 458
EP 463
DI 10.1016/j.ceb.2011.04.006
PG 6
WC Cell Biology
SC Cell Biology
GA 815HE
UT WOS:000294515900013
PM 21555211
ER
PT J
AU Karbowski, M
Youle, RJ
AF Karbowski, Mariusz
Youle, Richard J.
TI Regulating mitochondrial outer membrane proteins by ubiquitination and
proteasomal degradation
SO CURRENT OPINION IN CELL BIOLOGY
LA English
DT Article
ID YEAST SACCHAROMYCES-CEREVISIAE; DEPENDENT DEGRADATION; PROTEOLYTIC
CLEAVAGE; SPERM MITOCHONDRIA; APOPTOSIS; BAX; MITOPHAGY; FUSION; PARKIN;
MITOFUSIN
AB Mitochondrial outer membrane proteins have been found to be ubiquitinated and degraded by the proteasome. This process shares at least one component of the ERAD pathway of ER membrane protein degradation, the AAA ATPase cdc48/p97/VCP, thought to extract integral membrane proteins from the lipid bilayer and chaperone them to the proteasome. Proteasomal degradation of the outer mitochondrial membrane (OMM) protein Mcl1 regulates apoptosis whereas Parkin-mediated ubiquitination and degradation of Mitofusins can inhibit mitochondrial fusion and promote mitophagy. The breadth of OMM ubiquitin/proteasome substrates and the physiological relevance of their turnover are only beginning to be understood.
C1 [Karbowski, Mariusz] Univ Maryland, Sch Med, Ctr Biomed Engn & Technol, Baltimore, MD 21201 USA.
[Karbowski, Mariusz] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA.
[Youle, Richard J.] NINDS, Biochem Sect, NIH, Bethesda, MD 20892 USA.
RP Karbowski, M (reprint author), Univ Maryland, Sch Med, Ctr Biomed Engn & Technol, Baltimore, MD 21201 USA.
EM mkarbowski@umaryland.edu; youler@ninds.nih.gov
FU Intramural NIH HHS [ZIA NS002859-19]
NR 65
TC 78
Z9 80
U1 1
U2 14
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0955-0674
J9 CURR OPIN CELL BIOL
JI Curr. Opin. Cell Biol.
PD AUG
PY 2011
VL 23
IS 4
BP 476
EP 482
DI 10.1016/j.ceb.2011.05.007
PG 7
WC Cell Biology
SC Cell Biology
GA 815HE
UT WOS:000294515900015
PM 21705204
ER
PT J
AU Tan, ZS
Beiser, AS
Fox, CS
Au, R
Himali, JJ
Debette, S
DeCarli, C
Vasan, RS
Wolf, PA
Seshadri, S
AF Tan, Zaldy S.
Beiser, Alexa S.
Fox, Caroline S.
Au, Rhoda
Himali, Jayandra J.
Debette, Stephanie
DeCarli, Charles
Vasan, Ramachandran S.
Wolf, Philip A.
Seshadri, Sudha
TI Association of Metabolic Dysregulation With Volumetric Brain Magnetic
Resonance Imaging and Cognitive Markers of Subclinical Brain Aging in
Middle-Aged Adults The Framingham Offspring Study
SO DIABETES CARE
LA English
DT Article
ID IMPAIRED GLUCOSE-TOLERANCE; STROKE RISK PROFILE; DIABETES-MELLITUS;
ALZHEIMER-DISEASE; OLDER-ADULTS; DEMENTIA; INSULIN; PERFORMANCE
AB OBJECTIVE-Diabetic and prediabtic states, including insulin resistance, fasting hyperglycemia, and hyperinsulinemia, are associated with metabolic dysregulation. These components have been individually linked to increased risks of cognitive decline and Alzheimer's disease. We aimed to comprehensively relate all of the components of metabolic dysregulation to cognitive function and brain magnetic resonance imaging (MRI) in middle-aged adults.
RESEARCH DESIGN AND METHODS-Framingham Offspring participants who underwent volumetric MRI and detailed cognitive testing and were free of clinical stroke and dementia during examination 7 (1998-2001) constituted our study sample (n = 2,439; 1,311 women; age 61 +/- 9 years). We related diabetes, homeostasis model assessment of insulin resistance (HOMA-IR), fasting insulin, and glycohemoglobin levels to cross-sectional MRI measures of total cerebral brain volume (TCBV) and hippocampal volume and to verbal and visuospatial memory and executive function. We serially adjusted for age, sex, and education alone (model A), additionally for other vascular risk factors (model B), and finally, with the inclusion of apolipoprotein E-epsilon 4, plasma homocysteine, C-reactive protein, and interleukin-6 (model C).
RESULTS-We observed an inverse association between all indices of metabolic dysfunction and TCBV in all models (P < 0.030). The observed difference in TCBV between participants with and without diabetes was equivalent to approximately 6 years of chronologic aging. Diabetes and elevated glycohemoglobin, HOMA-IR, and fasting insulin were related to poorer executive function scores (P < 0.038), whereas only HOMA-IR and fasting insulin were inversely related to visuospatial memory (P < 0.007).
CONCLUSIONS-Metabolic dysregulation, especially insulin resistance, was associated with lower brain volumes and executive function in a large, relatively healthy, middle-aged, community-based cohort.
C1 [Tan, Zaldy S.] Vet Adm Boston Healthcare Syst, Ctr Geriatr Res Educ & Clin, Boston, MA USA.
[Tan, Zaldy S.] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA.
[Tan, Zaldy S.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
[Tan, Zaldy S.; Beiser, Alexa S.; Fox, Caroline S.; Au, Rhoda; Himali, Jayandra J.; Vasan, Ramachandran S.; Wolf, Philip A.; Seshadri, Sudha] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Beiser, Alexa S.; Au, Rhoda; Debette, Stephanie; Wolf, Philip A.; Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Beiser, Alexa S.; Himali, Jayandra J.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Hypertens & Metab, Boston, MA 02115 USA.
[DeCarli, Charles] Univ Calif Davis, Dept Neurol, Davis, CA 95616 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
RP Tan, ZS (reprint author), Vet Adm Boston Healthcare Syst, Ctr Geriatr Res Educ & Clin, Boston, MA USA.
EM ztan@hms.harvard.edu
OI Seshadri, Sudha/0000-0001-6135-2622; Au, Rhoda/0000-0001-7742-4491;
Ramachandran, Vasan/0000-0001-7357-5970; Beiser,
Alexa/0000-0001-8551-7778; /0000-0003-1391-9481
FU Framingham Heart Study's National Heart, Lung, and Blood Institute
[N01-HC-25195]; National Institutes of Health, National Institute of
Neurologic Disorders and Stroke [R01-NS-17950]; National Institute on
Aging [R01-AG-16495, AG-08122, AG-033193, AG-031287];
Bettencourt-Schueller Foundation
FX This work was supported by the Framingham Heart Study's National Heart,
Lung, and Blood Institute contract (N01-HC-25195) and by grants from the
National Institutes of Health, National Institute of Neurologic
Disorders and Stroke (R01-NS-17950) and from the National Institute on
Aging (R01-AG-16495; AG-08122; AG-033193; AG-031287). S.D. received an
award from the Bettencourt-Schueller Foundation.
NR 25
TC 52
Z9 53
U1 0
U2 7
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD AUG
PY 2011
VL 34
IS 8
BP 1766
EP 1770
DI 10.2337/dc11-0308
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 809EU
UT WOS:000294035400016
PM 21680719
ER
PT J
AU Sosenko, JM
Skyler, JS
Mahon, J
Krischer, JP
Beam, CA
Boulware, DC
Greenbaum, CJ
Rafkin, LE
Cowie, C
Cuthbertson, D
Palmer, JP
AF Sosenko, Jay M.
Skyler, Jay S.
Mahon, Jeffrey
Krischer, Jeffrey P.
Beam, Craig A.
Boulware, David C.
Greenbaum, Carla J.
Rafkin, Lisa E.
Cowie, Catherine
Cuthbertson, David
Palmer, Jerry P.
CA Type 1 Diabet TrialNet Study Grp
Diabet Prevention Trial-Type Study
TI Validation of the Diabetes Prevention Trial-Type 1 Risk Score in the
Trial Net Natural History Study
SO DIABETES CARE
LA English
DT Article
ID ACCELERATOR HYPOTHESIS; TRIAL-TYPE-1; INSULIN
AB OBJECTIVE-We assessed the accuracy of the Diabetes Prevention Trial Type 1 Risk Score (DPTRS), developed from the Diabetes Prevention Trial Type 1 (DPT-1), in the Trial Net Natural History Study (TNNHS).
RESEARCH DESIGN AND METHODS-Prediction accuracy of the DPTRS was assessed with receiver-operating characteristic curve areas. The type 1 diabetes cumulative incidence within the DPTRS intervals was compared between the TNNHS and DPT-1 cohorts.
RESULTS-Receiver-operating characteristic curve areas for the DPTRS were substantial in the TNNHS (P < 0.001 at both 2 and 3 years). The type 1 diabetes cumulative incidence did not differ significantly between the TNNHS and DPT-1 cohorts within DPTRS intervals. In the TNNHS, 2-year and 3-year risks were low for DPTRS intervals <6.50 (<0.10 and <0.20, respectively). Thresholds >= 7.50 were indicative of high risk in both cohorts (2-year risks: 0.49 in the TNNHS and 0.51 in DPT-1).
CONCLUSIONS-The DPTRS is an accurate and robust predictor of type 1 diabetes in autoantibody-positive populations.
C1 [Sosenko, Jay M.; Skyler, Jay S.; Rafkin, Lisa E.] Univ Miami, Div Endocrinol, Miami, FL 33152 USA.
[Mahon, Jeffrey] Univ Western Ontario, Dept Epidemiol & Biostat, London, ON N6A 3K7, Canada.
[Krischer, Jeffrey P.; Beam, Craig A.; Boulware, David C.] Univ S Florida, Div Informat & Biostat, Tampa, FL USA.
[Greenbaum, Carla J.] Benaroya Res Inst Virginia Mason, Seattle, WA USA.
[Cowie, Catherine] NIDDK, NIH, Bethesda, MD USA.
[Cuthbertson, David] Univ S Florida, Pediat Epidemiol Ctr, Tampa, FL USA.
[Palmer, Jerry P.] Univ Washington, Div Metab Endocrinol & Nutr, Vet Adm Puget Sound Hlth Care Syst, Seattle, WA 98195 USA.
RP Sosenko, JM (reprint author), Univ Miami, Div Endocrinol, Miami, FL 33152 USA.
EM jsosenko@med.miami.edu
RI Skyler, Jay/F-4211-2016
FU National Institutes of Health through the National Institute of Diabetes
and Digestive and Kidney Diseases; National Institute of Allergy and
Infectious Diseases; Eunice Kennedy Shriver National Institute of Child
Health and Human Development; National Center for Research Resources;
Juvenile Diabetes Research Foundation International; American Diabetes
Association
FX TrialNet is a clinical trials network funded by the National Institutes
of Health through the National Institute of Diabetes and Digestive and
Kidney Diseases, the National Institute of Allergy and Infectious
Diseases, the Eunice Kennedy Shriver National Institute of Child Health
and Human Development, the National Center for Research Resources, the
Juvenile Diabetes Research Foundation International, and the American
Diabetes Association.
NR 11
TC 17
Z9 17
U1 0
U2 1
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD AUG
PY 2011
VL 34
IS 8
BP 1785
EP 1787
DI 10.2337/dc11-0641
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 809EU
UT WOS:000294035400019
PM 21680724
ER
PT J
AU Murray, AM
Barzilay, JI
Lovato, JF
Williamson, JD
Miller, ME
Marcovina, S
Launer, LJ
AF Murray, Anne M.
Barzilay, Joshua I.
Lovato, James F.
Williamson, Jeff D.
Miller, Michael E.
Marcovina, Santica
Launer, Lenore J.
CA Action Control Cardiovasc Risk Dia
TI Biomarkers of Renal Function and Cognitive Impairment in Patients With
Diabetes
SO DIABETES CARE
LA English
DT Article
ID GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; CYSTATIN-C;
ALZHEIMERS-DISEASE; DEMENTIA; DECLINE; HEALTH; ALBUMINURIA; PREVALENCE;
COMMUNITY
AB OBJECTIVE-Kidney disease is associated with cognitive impairment in studies of nondiabetic adults. We examined the cross-sectional relation between three measures of renal function and performance on four measures of cognitive function in the Action to Control Cardiovascular Risk in Diabetes Memory in Diabetes (ACCORD-MIND) study.
RESEARCH DESIGN AND METHODS-The relationships among estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2) (n = 2,968), albumin/creatinine ratio (ACR) >= 30 mu g/mg (n = 2,957), and cystatin C level >1.0 mg/L (n = 532) with tertile of performance on the Mini-Mental State Examination, Rey Auditory Verbal Learning Test (RAVLT), Digit Symbol Substitution Test (DSST), and Stroop Test of executive function were measured.
RESULTS-In adjusted logistic regression models, ACR >= 30 mu g/mg was associated with performance in the lowest tertile, compared with the highest two tertiles, on the RAVLT (odds ratio 1.30, 95% CI 1.09-1.56, P = 0.006), equivalent to 3.6 years of aging, and on the DSST (1.47, 1.20-1.80, P = 0.001), equivalent to 3.7 years of aging. Cystatin C >1.0 mg/L was borderline associated with the lowest tertile on the DSST (1.81, 0.93-3.55, P = 0.08) and Stroop (1.78, 0.97-3.23, P = 0.06) in adjusted models. eGFR was not associated with any measure of cognitive performance.
CONCLUSIONS-In diabetic people with HbA(1c) >7.5% at high risk for cardiovascular disease, decreased cognitive function was associated with kidney disease as measured by ACR, a measure of microvascular endothelial pathology, and cystatin C, a marker of eGFR.
C1 [Murray, Anne M.] Hennepin Cty Med Ctr, Dept Med, Minneapolis, MN 55415 USA.
[Murray, Anne M.] Minneapolis Med Res Fdn Inc, Minneapolis, MN USA.
[Barzilay, Joshua I.] Kaiser Permanente Georgia, Atlanta, GA USA.
[Barzilay, Joshua I.] Emory Univ, Sch Med, Div Endocrinol, Atlanta, GA USA.
[Lovato, James F.; Miller, Michael E.] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
[Williamson, Jeff D.] Wake Forest Univ, Bowman Gray Sch Med, Dept Med, Roena Kulynych Ctr Memory & Cognit Res, Winston Salem, NC 27103 USA.
[Williamson, Jeff D.] Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Roena Kulynych Ctr Memory & Cognit Res, Winston Salem, NC 27103 USA.
[Marcovina, Santica] Univ Washington, NW Lipid Metab & Diabet Res Labs, Seattle, WA 98195 USA.
[Launer, Lenore J.] NIA, Lab Epidemiol, NIH, Bethesda, MD 20892 USA.
RP Murray, AM (reprint author), Hennepin Cty Med Ctr, Dept Med, Minneapolis, MN 55415 USA.
EM amurray@cdrg.org
FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-95178,
N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183,
N01-HC-95184, IAA Y1-HC-9035, IAA Y1-HC-1010]; National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK); National Eye
Institute (NEI); National Institute on Aging (NIA), Bethesda, MD;
Centers for Disease Control and Prevention (CDC), Atlanta, GA; NIA/NHLBI
[NIHNHLBI-HC-99-16]; National Institutes of Health (NIH); NIA
FX This work was supported by contract nos. N01-HC-95178, N01-HC-95179,
N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184,
IAA Y1-HC-9035, and IAA Y1-HC-1010 from the National Heart, Lung, and
Blood Institute (NHLBI), with additional support from the National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the
National Eye Institute (NEI), the National Institute on Aging (NIA),
Bethesda, MD, and by the Centers for Disease Control and Prevention
(CDC), Atlanta, GA. This study was also supported by grant no.
NIHNHLBI-HC-99-16 from the NIA/NHLBI, by the National Institutes of
Health (NIH)-funded General Clinical Research Centers, and by the
Intramural Research Program at the NIA.
NR 25
TC 19
Z9 20
U1 0
U2 2
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD AUG
PY 2011
VL 34
IS 8
BP 1827
EP 1832
DI 10.2337/dc11-0186
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 809EU
UT WOS:000294035400028
PM 21715519
ER
PT J
AU Nash, TE
Mahanty, S
Garcia, HH
AF Nash, Theodore E.
Mahanty, Siddhartha
Garcia, Hector H.
CA Cysticercosis Grp Peru
TI Corticosteroid use in neurocysticercosis
SO EXPERT REVIEW OF NEUROTHERAPEUTICS
LA English
DT Review
DE central nervous system; corticosteroids; cysticercosis;
neurocysticercosis; seizures; Taenia solium
ID SOLITARY CYSTICERCUS GRANULOMA; CENTRAL-NERVOUS-SYSTEM; CALCIFIED
NEUROCYSTICERCOSIS; GLUCOCORTICOID-RECEPTOR; CEREBRAL CYSTICERCOSIS;
INFLAMMATORY RESPONSES; INTERCELLULAR-ADHESION; IMMUNE-RESPONSE;
TAENIA-SOLIUM; PLASMA-LEVELS
AB The cystic larvae of Taenia solium commonly infect the human nervous system, resulting in neurocysticercosis, a major contributor to seizure disorders in most of the world. Inflammation around the parasites is a hallmark of neurocysticercosis pathophysiology. Although mechanisms regulating this inflammation are poorly understood, anti-inflammatory drugs, particularly corticosteroids, have been long used alone or with anthelmintics to manage disease and limit neurological complications and perhaps damage to neural tissues. Only scarce controlled data exist to determine when and what type of corticosteroids and the treatment regime to use. This article revisits the mechanisms of action, rationale, evidence of benefit, safety and problems of corticosteroids in the context of neurocysticercosis, as well as alternative anti-inflammatory strategies to limit the damage caused by inflammation in the CNS.
C1 [Garcia, Hector H.] Univ Peruana Cayetano Heredia, Sch Sci, Dept Microbiol, Lima, Peru.
[Garcia, Hector H.] Univ Peruana Cayetano Heredia, Ctr Global Hlth Tumbes, Lima, Peru.
[Nash, Theodore E.; Mahanty, Siddhartha] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Garcia, Hector H.] Inst Ciencias Neurol, Cysticercosis Unit, Lima, Peru.
[Garcia, Hector H.] Inst Peruano Parasitol Clin & Expt, Lima, Peru.
RP Garcia, HH (reprint author), Univ Peruana Cayetano Heredia, Sch Sci, Dept Microbiol, Lima, Peru.
EM hgarcia@jhsph.edu
OI Mahanty, Siddhartha/0000-0003-1068-0524
FU US National Institute of Allergy and Infectious Diseases (NIAID), US NIH
FX Funding for this study was in part provided by the US National Institute
of Allergy and Infectious Diseases (NIAID), US NIH. 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 61
TC 20
Z9 21
U1 0
U2 5
PU EXPERT REVIEWS
PI LONDON
PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB,
ENGLAND
SN 1473-7175
J9 EXPERT REV NEUROTHER
JI Expert Rev. Neurother.
PD AUG
PY 2011
VL 11
IS 8
BP 1175
EP 1183
DI 10.1586/ERN.11.86
PG 9
WC Clinical Neurology; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 817DD
UT WOS:000294650400015
PM 21797658
ER
PT J
AU Nouraie, M
Cheng, K
Niu, XM
Moore-King, E
Fadojutimi-Akinsi, MF
Minniti, CP
Sable, C
Rana, S
Dham, N
Campbell, A
Ensing, G
Kato, GJ
Gladwin, MT
Castro, OL
Gordeuk, VR
AF Nouraie, Mehdi
Cheng, Kevin
Niu, Xiaomei
Moore-King, Evadne
Fadojutimi-Akinsi, Margaret F.
Minniti, Caterina P.
Sable, Craig
Rana, Sohail
Dham, Niti
Campbell, Andrew
Ensing, Gregory
Kato, Gregory J.
Gladwin, Mark T.
Castro, Oswaldo L.
Gordeuk, Victor R.
TI Predictors of osteoclast activity in patients with sickle cell disease
SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
LA English
DT Article
DE sickle cell disease; osteoclast activity; bone turnover; inflammation;
TRACP 5b; pulmonary complications
ID BONE-MINERAL DENSITY; BETA-THALASSEMIA MAJOR; CHRONIC KIDNEY-DISEASE;
ACID-PHOSPHATASE; PULMONARY-HYPERTENSION; IRON OVERLOAD; OXIDATIVE
STRESS; OSTEOPOROSIS; METABOLISM; RESORPTION
AB Background
Bone changes are common in sickle cell disease, but the pathogenesis is not fully understood. Tartrate-resistant acid phosphatase (TRACP) type 5b is produced by bone-resorbing osteoclasts. In other forms of hemolytic anemia, increased iron stores are associated with osteoporosis. We hypothesized that transfusional iron overload would be associated with increased osteoclast activity in patients with sickle cell disease.
Design and Methods
We examined tartrate-resistant acid phosphatase 5b concentrations in patients with sickle cell disease and normal controls of similar age and sex distribution at steady state. Serum tartrate-resistant acid phosphatase 5b concentration was measured using an immunocapture enzyme assay and plasma concentrations of other cytokines were assayed using the Bio-Plex suspension array system. Tricuspid regurgitation velocity, an indirect measure of systolic pulmonary artery pressure, was determined by echocardiography.
Results
Tartrate-resistant acid phosphatase 5b concentrations were higher in 58 adults with sickle cell disease than in 22 controls (medians of 4.4 versus 2.4 U/L, respectively; P=0.0001). Among the patients with sickle cell disease, tartrate-resistant acid phosphatase 5b independently correlated with blood urea nitrogen (standardized beta=0.40, P=0.003), interleukin-8 (standardized beta=0.30, P=0.020), and chemokine C-C motif ligand 5 (standardized beta=-0.28, P=0.031) concentrations, but not with serum ferritin concentration. Frequent blood transfusions (>10 units in life time) were not associated with higher tartrate-resistant acid phosphatase 5b levels in multivariate analysis. There were strong correlations among tartrate-resistant acid phosphatase 5b, alkaline phosphatase and tricuspid regurgitation velocity (r>0.35, P<0.001).
Conclusions
Patients with sickle cell disease have increased osteoclast activity as reflected by serum tartrate-resistant acid phosphatase 5b concentrations. Our results may support a potential role of inflammation rather than increased iron stores in stimulating osteoclast activity in sickle cell disease. The positive relationships among tartrate-resistant acid phosphatase 5b, alkaline phosphatase and tricuspid regurgitation velocity raise the possibility of a common pathway in the pulmonary and bone complications of sickle cell disease.
C1 [Nouraie, Mehdi; Cheng, Kevin; Niu, Xiaomei; Moore-King, Evadne; Fadojutimi-Akinsi, Margaret F.; Rana, Sohail; Castro, Oswaldo L.; Gordeuk, Victor R.] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA.
[Nouraie, Mehdi; Cheng, Kevin; Niu, Xiaomei; Moore-King, Evadne; Fadojutimi-Akinsi, Margaret F.; Rana, Sohail; Castro, Oswaldo L.; Gordeuk, Victor R.] Howard Univ, Dept Med, Washington, DC 20059 USA.
[Minniti, Caterina P.; Kato, Gregory J.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Sable, Craig; Dham, Niti] Childrens Natl Med Ctr, Div Cardiol, Washington, DC 20010 USA.
[Campbell, Andrew; Ensing, Gregory] Univ Michigan, Ann Arbor, MI 48109 USA.
[Gladwin, Mark T.] Univ Pittsburgh, Pittsburgh, PA USA.
RP Nouraie, M (reprint author), 1840 7th St NW,Room 201, Washington, DC 20001 USA.
EM snouraie@howard.edu
RI Kato, Gregory/I-7615-2014
OI Kato, Gregory/0000-0003-4465-3217
FU NHLBI [2 R25 HL003679-08, 1 R01 HL079912-02]; NCRR, NIH, Bethesda, MD
[2MOI RR10284-10]; National Institutes of Health [1ZIAHL006016]
FX supported in part by grant numbers 2 R25 HL003679-08 and 1 R01
HL079912-02 from NHLBI, by Howard University GCRC grant number 2MOI
RR10284-10 from NCRR, NIH, Bethesda, MD, and by the National Institutes
of Health intramural research program grant number 1ZIAHL006016.
NR 52
TC 6
Z9 6
U1 0
U2 1
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 AUG
PY 2011
VL 96
IS 8
BP 1092
EP 1098
DI 10.3324/haematol.2011.042499
PG 7
WC Hematology
SC Hematology
GA 818BA
UT WOS:000294722700005
PM 21546502
ER
PT J
AU Calvo, KR
Vinh, DC
Maric, I
Wang, WX
Noel, P
Stetler-Stevenson, M
Arthur, DC
Raffeld, M
Dutra, A
Pak, E
Myung, K
Hsu, AP
Hickstein, DD
Pittaluga, S
Holland, SM
AF Calvo, Katherine R.
Vinh, Donald C.
Maric, Irina
Wang, Weixin
Noel, Pierre
Stetler-Stevenson, Maryalice
Arthur, Diane C.
Raffeld, Mark
Dutra, Amalia
Pak, Evgenia
Myung, Kyungjae
Hsu, Amy P.
Hickstein, Dennis D.
Pittaluga, Stefania
Holland, Steven M.
TI Myelodysplasia in autosomal dominant and sporadic monocytopenia
immunodeficiency syndrome: diagnostic features and clinical implications
SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
LA English
DT Article
DE myelodysplasia; MDS; monocytopenia; mycobacterium avium complex;
MonoMAC; GATA2 deficiency
ID BONE-MARROW; MONOCLONAL GAMMOPATHY; MULTIPLE-MYELOMA; PLASMA-CELLS;
PROGNOSIS; LEUKEMIA; FIBROSIS
AB A novel, genetic immunodeficiency syndrome has been recently described, herein termed "MonoMAC". It is characterized by severe circulating monocytopenia, NK- and B- lymphocytopenia, severe infections with M. avium complex (MAC), and risk of progression to myelodysplasia/acute myelogenous leukemia. Detailed bone marrow analyses performed on 18 patients further define this disorder. The majority of patients had hypocellular marrows with reticulin fibrosis and multilineage dysplasia affecting the myeloid (72%), erythroid (83%) and megakaryocytic (100%) lineages. Cytogenetic abnormalities were present in 10 of 17 (59%). Despite B- lymphocytopenia, plasma cells were present but were abnormal (e.g. CD56(+)) in nearly half of cases. Increased T-cell large granular lymphocyte populations were present in 28% of patients. Chromosomal breakage studies, cell cycle checkpoint functions, and sequencing of TERT and K-RAS genes revealed no abnormalities. MonoMAC appears to be a unique, inherited syndrome of bone marrow failure. We describe distinctive bone marrow features to help in its recognition and diagnosis. (Clinicaltrials.gov identifiers: NCT00018044, NCT00923364, NCT01212055)
C1 [Calvo, Katherine R.; Maric, Irina; Wang, Weixin; Noel, Pierre] NIH, Hematol Sect, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Vinh, Donald C.; Hsu, Amy P.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Stetler-Stevenson, Maryalice; Arthur, Diane C.; Raffeld, Mark; Pittaluga, Stefania] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Myung, Kyungjae] NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
[Hickstein, Dennis D.] NCI, Expt Transplantat & Immunol Branch, CCR, Bethesda, MD 20892 USA.
RP Calvo, KR (reprint author), NIH, Hematol Sect, Dept Lab Med, Ctr Clin, 10 Ctr Dr,Bldg 10-2C390, Bethesda, MD 20892 USA.
EM calvok@mail.nih.gov
RI Calvo, Katherine/A-8109-2009;
OI Calvo, Katherine/0000-0002-0771-4191; VINH, DONALD/0000-0003-1347-7767
NR 21
TC 36
Z9 37
U1 0
U2 5
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 AUG
PY 2011
VL 96
IS 8
BP 1221
EP 1225
DI 10.3324/haematol.2011.041152
PG 5
WC Hematology
SC Hematology
GA 818BA
UT WOS:000294722700021
PM 21508125
ER
PT J
AU Chen, WJ
AF Chen, WanJun
TI Tregs in immunotherapy: opportunities and challenges
SO IMMUNOTHERAPY
LA English
DT Editorial Material
DE apoptosis; autoimmunity; Foxp3; immune tolerance; TGF-beta; Th17; Tregs
ID REGULATORY T-CELLS; TRANSCRIPTION FACTOR FOXP3; TGF-BETA; DENDRITIC
CELLS; SELF-TOLERANCE; IN-VIVO; DIFFERENTIATION; INDUCTION; T(H)17;
EXPRESSION
C1 Natl Inst Dent & Craniofacial Res, Mucosal Immunol Sect, OHB, NIH, Bethesda, MD 20892 USA.
RP Chen, WJ (reprint author), Natl Inst Dent & Craniofacial Res, Mucosal Immunol Sect, OHB, NIH, Bethesda, MD 20892 USA.
EM wchen@dir.nidcr.nih.gov
FU Intramural NIH HHS
NR 34
TC 7
Z9 8
U1 0
U2 1
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1750-743X
J9 IMMUNOTHERAPY-UK
JI Immunotherapy
PD AUG
PY 2011
VL 3
IS 8
BP 911
EP 914
DI 10.2217/IMT.11.79
PG 4
WC Immunology
SC Immunology
GA 816GH
UT WOS:000294586200001
PM 21843075
ER
PT J
AU Roy, A
Roy, M
Goldman, D
AF Roy, Alec
Roy, Monique
Goldman, David
TI Childhood Trauma and Depressive Symptoms in Type 1 Diabetes
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Article
ID SEROTONIN TRANSPORTER GENE; STRESSFUL LIFE EVENTS; POOR GLYCEMIC
CONTROL; MAJOR DEPRESSION; PSYCHIATRIC-DISORDERS; 5-HTTLPR POLYMORPHISM;
COMMUNITY SAMPLE; AFRICAN-AMERICANS; ABUSE; RISK
AB Background: To examine the relationship of childhood trauma to depressive symptoms in type 1 diabetes, a chronic disease in which the frequency of depression is increased.
Method: One hundred fifty African American patients with type 1 diabetes seen between August 1993 and January 1998 completed the Beck Depression Inventory and Childhood Trauma Questionnaire. They were also genotyped for a functional serotonin transporter promoter polymorphism (5-HTTLPR) that modulates resiliency. Patients who had Beck Depression Inventory scores above and below 14 were compared.
Results: Diabetic patients who had Beck Depression Inventory scores >= 14 had experienced significantly more different types of childhood trauma than those with Beck Depression Inventory scores < 14 (P < .001), independent of potential interaction with 5-HTTLPR genotype.
Conclusions: Childhood trauma appears to be a determinant of depressive symptoms in type I diabetes, independently of genotype of a functional locus modulating resiliency. J Clin Psychiatry 2011;72(8):1049-1053 (C) Copyright 2010 Physicians Postgraduate Press, Inc.
C1 [Roy, Alec] Hlth Care Syst, Psychiat Serv, New Jersey Vet Affairs, E Orange, NJ USA.
[Roy, Monique] Univ Med & Dent New Jersey, Sch Med, Newark, NJ 07103 USA.
[Goldman, David] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA.
RP Roy, A (reprint author), NJHCS, Psychiat Serv 116A, Dept Vet Affairs, 385 Tremont Ave, E Orange, NJ 07018 USA.
EM Alec.Roy@va.gov
NR 61
TC 1
Z9 1
U1 4
U2 10
PU PHYSICIANS POSTGRADUATE PRESS
PI MEMPHIS
PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA
SN 0160-6689
EI 1555-2101
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD AUG
PY 2011
VL 72
IS 8
BP 1049
EP 1053
DI 10.4088/JCP.09m05857b1u
PG 5
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 817FL
UT WOS:000294656600004
PM 21034694
ER
PT J
AU Bonne, O
Gill, JM
Luckenbaugh, DA
Collins, C
Owens, MJ
Alesci, S
Neumeister, A
Yuan, PX
Kinkead, B
Manji, HK
Charney, DS
Vythilingam, M
AF Bonne, Omer
Gill, Jessica Mary
Luckenbaugh, David A.
Collins, Carlos
Owens, Michael J.
Alesci, Salvadore
Neumeister, Alexander
Yuan, Peixiong
Kinkead, Becky
Manji, Huesseni K.
Charney, Dennis S.
Vythilingam, Meena
TI Corticotropin-Releasing Factor, Interleukin-6, Brain-Derived
Neurotrophic Factor, Insulin-Like Growth Factor-1, and Substance P in
the Cerebrospinal Fluid of Civilians With Posttraumatic Stress Disorder
Before and After Treatment With Paroxetine
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Article
ID MAJOR DEPRESSION; HIPPOCAMPAL VOLUME; SEROTONIN REUPTAKE; PLACEBO;
HORMONE; SERTRALINE; VETERANS; PLASMA; SERUM; PTSD
AB Background: Posttraumatic stress disorder (PTSD) is associated with altered concentrations of stress-related neurohormones, neurotrophins, and neuropeptides in plasma and serum; however, few studies have examined central alterations of these measures in individuals with PTSD. Furthermore, no study to date has evaluated the effects of successful antidepressant treatment on cerebrospinal fluid (CSF) abnormalities in PTSD.
Method: Sixteen medication-free outpatients with chronic PTSD (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) due to physical and/or sexual abuse or motor vehicle accidents (mean +/- SD age = 36 +/- 11.4 years, 12 women) and 11 nontraumatized healthy subjects (mean SD age = 35.3 +/- 13.1 years, 7 women) underwent a lumbar puncture for collection of CSF. Seven PTSD patients had a repeat lumbar puncture 12 weeks later, after successful treatment of PTSD with paroxetine. CSF was analyzed for corticotropin-releasing factor (CRF), interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and substance P concentrations. The study was conducted between January 2003 and August 2004.
Results: Compared to nontraumatized healthy controls, patients with chronic PTSD had similar pretreatment concentrations of CSF CRF, IL-6, BDNF, IGF-1, and substance P. Posttreatment CSF measures did not change significantly in patients whose symptoms remitted with paroxetine.
Conclusions: Chronic, moderate PTSD due to civilian trauma, without psychotic symptoms and without significant rates of comorbid depression, alcohol dependence, or substance dependence, is not associated with abnormalities in CSF CRF, IL-6, BDNF, IGF-1, or substance P levels. Despite substantial reduction in PTSD symptoms, antidepressant treatment does not alter normal central concentrations of these neurochemicals, with the possible exception of substance P. J Clin Psychiatry 2011;72(8):1124-1128 (C) Copyright 2010 Physicians Postgraduate Press, Inc.
C1 [Bonne, Omer] Hadassah Hebrew Univ, Med Ctr, Dept Psychiat, IL-91120 Jerusalem, Israel.
[Gill, Jessica Mary] NINR, NIH, Bethesda, MD 20892 USA.
[Luckenbaugh, David A.; Collins, Carlos; Yuan, Peixiong; Manji, Huesseni K.; Vythilingam, Meena] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA.
[Owens, Michael J.; Kinkead, Becky] Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA.
[Alesci, Salvadore] NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA.
[Neumeister, Alexander] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA.
[Charney, Dennis S.] Mt Sinai Sch Med, New York, NY USA.
RP Bonne, O (reprint author), Hadassah Hebrew Univ, Med Ctr, Dept Psychiat, POB 12000, IL-91120 Jerusalem, Israel.
EM bonne@hadassah.org.il
RI Owens, Michael/G-5191-2012
FU NIMH [MH42088]; NIMH, NIH, Bethesda, Maryland
FX Funding for CRF assays was provided through NIMH grant MH42088 awarded
to Dr Owens. This research was supported by the Intramural Program of
the NIMH, NIH, Bethesda, Maryland.
NR 34
TC 28
Z9 30
U1 2
U2 9
PU PHYSICIANS POSTGRADUATE PRESS
PI MEMPHIS
PA P O BOX 240008, MEMPHIS, TN 38124 USA
SN 0160-6689
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD AUG
PY 2011
VL 72
IS 8
BP 1124
EP 1128
DI 10.4088/JCP.09m05106blu
PG 5
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 817FL
UT WOS:000294656600012
PM 21208596
ER
PT J
AU Mullin, PM
Bray, A
Schoenberg, F
MacGibbon, KW
Romero, R
Goodwin, TM
Fejzo, MS
AF Mullin, P. M.
Bray, A.
Schoenberg, F.
MacGibbon, K. W.
Romero, R.
Goodwin, T. M.
Fejzo, M. S.
TI Prenatal exposure to hyperemesis gravidarum linked to increased risk of
psychological and behavioral disorders in adulthood
SO JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE
LA English
DT Article
DE anxiety; bipolar; depression; hyperemesis gravidarum; outcome
ID PREGNANCY; DEFICIENCY; NAUSEA; OUTCOMES; CHILDREN; ANXIETY; LEPTIN;
WOMEN; LIFE; RATS
AB Hyperemesis gravidarum (HG), severe nausea and vomiting of pregnancy, is characterized by long-term maternal stress, undernutrition and dehydration. While maternal stress and malnutrition of pregnancy are linked to poor neonatal outcome and associated with poor adult health, long-term outcome of fetal exposure to HG has never been explored. The purpose of this study is to determine whether long-term emotional and behavioral diagnoses may be associated with fetal exposure to HG. Emotional and behavioral diagnoses of adults born of a pregnancy complicated by HG were compared to diagnoses from non-exposed controls. Offspring exposed to HG in utero were significantly more likely to have a psychological and behavioral disorder (OR=3.6, P < 0.0001) with diagnoses primarily of depression, bipolar disorder and anxiety. In utero exposure to HG may lead to increased risks of psychological and behavioral disorders in the offspring.
C1 [Mullin, P. M.; Goodwin, T. M.; Fejzo, M. S.] Univ So Calif, Keck Sch Med, Dept Maternal Fetal Med, Los Angeles, CA 90033 USA.
[Bray, A.; Schoenberg, F.] Univ Calif Los Angeles, Dept Stat, Los Angeles, CA USA.
[MacGibbon, K. W.] Hyperemesis Educ & Res Fdn, Leesburg, VA USA.
[Romero, R.] NICHD, Dept Hlth & Human Serv, NIH, DHHS,Perinatol Res Branch, Bethesda, MD USA.
[Romero, R.] NICHD, Dept Hlth & Human Serv, NIH, DHHS,Perinatol Res Branch, Detroit, MI USA.
[Fejzo, M. S.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA.
RP Fejzo, MS (reprint author), 5535 MRL Bldg,675 Charles E Young Dr S, Los Angeles, CA 90095 USA.
EM mfejzo@mednet.ucla.edu
OI MacGibbon, Kimber/0000-0002-6534-3114
FU National Institute of Child Health and Human Development, National
Institute of Health; Department of Health and Human Services
FX This research was supported in part by the Intramural Research Program
of the National Institute of Child Health and Human Development,
National Institute of Health and Department of Health and Human
Services.
NR 32
TC 12
Z9 13
U1 1
U2 6
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 2040-1744
J9 J DEV ORIG HLTH DIS
JI J. Dev. Orig. Health Dis.
PD AUG
PY 2011
VL 2
IS 4
BP 200
EP 204
DI 10.1017/S2040174411000249
PG 5
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 817JK
UT WOS:000294668100003
PM 25141163
ER
PT J
AU Kolar, SL
Nagarajan, V
Oszmiana, A
Rivera, FE
Miller, HK
Davenport, JE
Riordan, JT
Potempa, J
Barber, DS
Koziel, J
Elasri, MO
Shaw, LN
AF Kolar, Stacey L.
Nagarajan, Vijayaraj
Oszmiana, Anna
Rivera, Frances E.
Miller, Halie K.
Davenport, Jessica E.
Riordan, James T.
Potempa, Jan
Barber, David S.
Koziel, Joanna
Elasri, Mohamed O.
Shaw, Lindsey N.
TI NsaRS is a cell-envelope-stress-sensing two-component system of
Staphylococcus aureus
SO MICROBIOLOGY-SGM
LA English
DT Article
ID ANAEROBIC GENE-EXPRESSION; REGULATORY SYSTEM; BACILLUS-SUBTILIS;
LIPID-II; METHICILLIN-RESISTANT; ANTIMICROBIAL AGENTS; MODULATES
VIRULENCE; TRANSDUCTION SYSTEM; BIOFILM FORMATION; ESCHERICHIA-COLI
AB Staphylococcus aureus possesses 16 two-component systems (TCSs), two of which (GraRS and NsaRS) belong to the intramembrane-sensing histidine kinase (IM-HK) family, which is conserved within the firmicutes. NsaRS has recently been documented as being important for nisin resistance in S. aureus. In this study, we present a characterization of NsaRS and reveal that, as with other IM-HK TCSs, it responds to disruptions in the cell envelope. Analysis using a lacZ reporter gene fusion demonstrated that nsaRS expression is upregulated by a variety of cell-envelope-damaging antibiotics, including phosphomycin, ampicillin, nisin, gramicidin, carbonyl cyanide m-chlorophenylhydrazone and penicillin G. Additionally, we reveal that NsaRS regulates a downstream transporter NsaAB during nisin-induced stress. NsaS mutants also display a 200-fold decreased ability to develop resistance to the cell-wall-targeting antibiotic bacitracin. Microarray analysis reveals that the transcription of 245 genes is altered in an nsaS mutant, with the vast majority being downregulated. Included within this list are genes involved in transport, drug resistance, cell envelope synthesis, transcriptional regulation, amino acid metabolism and virulence. Using inductively coupled plasma-MS we observed a decrease in intracellular divalent metal ions in an nsaS mutant when grown under low abundance conditions. Characterization of cells using electron microscopy reveals that nsaS mutants have alterations in cell envelope structure. Finally, a variety of virulence-related phenotypes are impaired in nsaS mutants, including biofilm formation, resistance to killing by human macrophages and survival in whole human blood. Thus, NsaRS is important in sensing cell damage in S. aureus and functions to reprogram gene expression to modify cell envelope architecture, facilitating adaptation and survival.
C1 [Kolar, Stacey L.; Rivera, Frances E.; Miller, Halie K.; Davenport, Jessica E.; Riordan, James T.; Shaw, Lindsey N.] Univ S Florida, Dept Cell Biol Microbiol & Mol Biol, Tampa, FL 33620 USA.
[Nagarajan, Vijayaraj] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, Bethesda, MD 20892 USA.
[Oszmiana, Anna; Potempa, Jan; Koziel, Joanna] Jagiellonian Univ, Dept Microbiol, Fac Biochem Biophys & Biotechnol, Krakow, Poland.
[Barber, David S.] Univ Florida, Ctr Environm & Human Toxicol, Gainesville, FL USA.
[Elasri, Mohamed O.] Univ So Mississippi, Dept Biol Sci, Hattiesburg, MS 39406 USA.
RP Shaw, LN (reprint author), Univ S Florida, Dept Cell Biol Microbiol & Mol Biol, Tampa, FL 33620 USA.
EM shaw@usf.edu
RI Oszmiana, Anna/F-6915-2015;
OI Oszmiana, Anna/0000-0003-1501-4184; , /0000-0003-0380-9289; Shaw,
Lindsey/0000-0002-0629-8990
FU National Institute of Allergies and Infectious Diseases
[1R21AI090350-01]
FX We are grateful to Dr Mark Smeltzer and Dr Karen Beenken for the sharing
of bacterial strains and methodologies, and to Dr Stanley Stevens for
help with data analysis. We gratefully acknowledge the help of Mr Edward
Haller of the Integrative Biology Electron Microscopy Core Facility at
the University of South Florida. This study was supported in part the
National Institute of Allergies and Infectious Diseases, grant
1R21AI090350-01 (L. N. S.).
NR 58
TC 37
Z9 37
U1 1
U2 13
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 1350-0872
J9 MICROBIOL-SGM
JI Microbiology-(UK)
PD AUG
PY 2011
VL 157
BP 2206
EP 2219
DI 10.1099/mic.0.049692-0
PN 8
PG 14
WC Microbiology
SC Microbiology
GA 813UQ
UT WOS:000294396100003
PM 21565927
ER
PT J
AU Hallett, M
AF Hallett, Mark
TI Bradykinesia: Why Do Parkinson's Patients Have It and What Trouble Does
It Cause?
SO MOVEMENT DISORDERS
LA English
DT Editorial Material
ID DISEASE; MOVEMENTS; PATHOPHYSIOLOGY; GAIT
C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Rm 7D37,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA.
EM hallettm@ninds.nih.gov
FU Intramural NIH HHS
NR 23
TC 9
Z9 9
U1 0
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD AUG 1
PY 2011
VL 26
IS 9
BP 1579
EP 1581
DI 10.1002/mds.23730
PG 3
WC Clinical Neurology
SC Neurosciences & Neurology
GA 812AX
UT WOS:000294261200001
PM 21547949
ER
PT J
AU Benninger, DH
Lomarev, M
Lopez, G
Pal, N
Luckenbaugh, DA
Hallett, M
AF Benninger, David H.
Lomarev, Mikhail
Lopez, Grisel
Pal, Natassja
Luckenbaugh, David A.
Hallett, Mark
TI Transcranial Direct Current Stimulation for the Treatment of Focal Hand
Dystonia
SO MOVEMENT DISORDERS
LA English
DT Article
DE transcranial direct current stimulation (tDCS); noninvasive brain
stimulation; therapeutic study; focal hand dystonia
ID PRIMARY MOTOR CORTEX; WRITERS CRAMP; MAGNETIC STIMULATION; BRAIN
AB The treatment of writer's cramp, a task-specific focal hand dystonia, needs new approaches. A deficiency of inhibition in the motor cortex might cause writer's cramp. Transcranial direct current stimulation modulates cortical excitability and may provide a therapeutic alternative. In this randomized, double-blind, sham-controlled study, we investigated the efficacy of cathodal stimulation of the contralateral motor cortex in 3 sessions in 1 week. Assessment over a 2-week period included clinical scales, subjective ratings, kinematic handwriting analysis, and neurophysiological evaluation. Twelve patients with unilateral dystonic writer's cramp were investigated; 6 received transcranial direct current and 6 sham stimulation. Cathodal transcranial direct current stimulation had no favorable effects on clinical scales and failed to restore normal handwriting kinematics and cortical inhibition. Subjective worsening remained unexplained, leading to premature study termination. Repeated sessions of cathodal transcranial direct current stimulation of the motor cortex yielded no favorable results supporting a therapeutic potential in writer's cramp. (C) 2011 Movement Disorder Society
C1 [Benninger, David H.; Lomarev, Mikhail; Lopez, Grisel; Pal, Natassja; Hallett, Mark] NIH, Med Neurol Branch, Bethesda, MD 20892 USA.
[Benninger, David H.] Univ Basel Hosp, Dept Neurol, CH-4031 Basel, Switzerland.
[Lomarev, Mikhail] VM Bekhterev Psychoneurol Res Inst, St Petersburg, Russia.
[Luckenbaugh, David A.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA.
[Luckenbaugh, David A.] NIMH, NIH, Bethesda, MD 20892 USA.
RP Benninger, DH (reprint author), CHU Vaudois, Dept Neurol, Rue Bugnon 46, CH-1011 Lausanne, Switzerland.
EM David.Benninger@chuv.ch
RI Benninger, David/A-8157-2015
OI Benninger, David/0000-0002-1049-9533
FU NINDS, NIH
FX This research was supported by the Intramural Research Program of the
NINDS, NIH.
NR 21
TC 26
Z9 27
U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD AUG 1
PY 2011
VL 26
IS 9
BP 1698
EP 1702
DI 10.1002/mds.23691
PG 5
WC Clinical Neurology
SC Neurosciences & Neurology
GA 812AX
UT WOS:000294261200019
PM 21495074
ER
PT J
AU Zoppoli, G
Douarre, C
Rosa, ID
Liu, HF
Reinhold, W
Pommier, Y
AF Zoppoli, Gabriele
Douarre, Celine
Rosa, Ilaria Dalla
Liu, Hongfang
Reinhold, William
Pommier, Yves
TI Coordinated regulation of mitochondrial topoisomerase IB with
mitochondrial nuclear encoded genes and MYC
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID EXPRESSION PROFILES; DNA TOPOISOMERASES; MESSENGER-RNA; TARGET GENES;
CELL LINES; E-BOX; CANCER; NUCLEOIDS; PANEL; IDENTIFICATION
AB Mitochondrial DNA (mtDNA) is entirely dependent on nuclear genes for its transcription and replication. One of these genes is TOP1MT, which encodes the mitochondrial DNA topoisomerase IB, involved in mtDNA relaxation. To elucidate TOP1MT regulation, we performed genome-wide profiling across the 60-cell line panel (the NCI-60) of the National Cancer Institute Developmental Therapeutics Program. We show that TOP1MT mRNA expression varies widely across these cell lines with the highest levels in leukemia (HL-60, K-562) and melanoma (SK-MEL-28), intermediate levels in breast (MDA-MB-231), ovarian (OVCAR) and colon (HCT-116, HCT-15, KM-12), and lowest levels in renal (ACHN, A498), prostate (PC-3, DU-145) and central nervous system cell lines (SF-539, SF-268, SF-295). Genome-wide analyses show that TOP1MT expression is significantly correlated with the other mitochondrial nuclear-encoded genes including the mitochondrial nucleoid genes, and demonstrate an overall co-regulation of the mitochondrial nuclear-encoded genes. We also find very high correlation between the expression of TOP1MT and the proto-oncogene MYC (c-myc). TOP1MT contains E-boxes (c-myc binding sites) and TOP1MT transcription follows MYC up-and down-regulation by MYC promoter activation and siRNA against MYC. Our finding implicates MYC as a novel regulator of TOP1MT and confirms its role as a master regulator of MNEGs and mitochondrial nucleoids.
C1 [Zoppoli, Gabriele; Douarre, Celine; Rosa, Ilaria Dalla; Liu, Hongfang; Reinhold, William; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20890 USA.
[Zoppoli, Gabriele] Univ Genoa, Dept Internal Med DiMI, Genoa, Italy.
RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20890 USA.
EM gabriele.zoppoli@unige.it; pommier@nih.gov
RI Zoppoli, Gabriele/B-6935-2016
OI Zoppoli, Gabriele/0000-0003-3890-5588
FU National Cancer Institute, Center for Cancer Research, National
Institutes of Health [Z01 BC 006161-17LMP]; University of Genova,
Genova, Italy
FX Funding for open access charge: National Cancer Institute Intramural
Program, Center for Cancer Research, National Institutes of Health (Z01
BC 006161-17LMP); University of Genova, Genova, Italy, PhD fellowship
grant XXIII Ciclo (to G.Z.).
NR 52
TC 12
Z9 12
U1 0
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD AUG
PY 2011
VL 39
IS 15
BP 6620
EP 6632
DI 10.1093/nar/gkr208
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 815UQ
UT WOS:000294555800033
PM 21531700
ER
PT J
AU Kenyon, JC
Tanner, SJ
Legiewicz, M
Phillip, PS
Rizvi, TA
Le Grice, SFJ
Lever, AML
AF Kenyon, Julia C.
Tanner, Sian J.
Legiewicz, Michal
Phillip, Pretty S.
Rizvi, Tahir A.
Le Grice, Stuart F. J.
Lever, Andrew M. L.
TI SHAPE analysis of the FIV Leader RNA reveals a structural switch
potentially controlling viral packaging and genome dimerization
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID FELINE IMMUNODEFICIENCY VIRUS; KISSING-LOOP DOMAIN; HIV-1 RNA; MEDIATED
DIMERIZATION; SECONDARY STRUCTURE; NUCLEOTIDE-SEQUENCE; DIMER LINKAGE;
GAG SEQUENCES; ENCAPSIDATION; INFECTION
AB Feline immunodeficiency virus (FIV) infects many species of cat, and is related to HIV, causing a similar pathology. High-throughput selective 2' hydroxyl acylation analysed by primer extension (SHAPE), a technique that allows structural interrogation at each nucleotide, was used to map the secondary structure of the FIV packaging signal RNA. Previous studies of this RNA showed four conserved stem-loops, extensive long-range interactions (LRIs) and a small, palindromic stem-loop (SL5) within the gag open reading frame (ORF) that may act as a dimerization initiation site (DIS), enabling the virus to package two copies of its genome. Our analyses of wild-type (wt) and mutant RNAs suggest that although the four conserved stem-loops are static structures, the 5' and 3' regions previously shown to form LRI also adopt an alternative, yet similarly conserved conformation, in which the putative DIS is occluded, and which may thus favour translational and splicing functions over encapsidation. SHAPE and in vitro dimerization assays were used to examine SL5 mutants. Dimerization contacts appear to be made between palindromic loop sequences in SL5. As this stem-loop is located within the gag ORF, recognition of a dimeric RNA provides a possible mechanism for the specific packaging of genomic over spliced viral RNAs.
C1 [Kenyon, Julia C.; Tanner, Sian J.; Lever, Andrew M. L.] Univ Cambridge, Addenbrookes Hosp, Dept Med, Cambridge CB2 0QQ, England.
[Legiewicz, Michal; Le Grice, Stuart F. J.] NCI, RT Biochem Sect, HIV Drug Resistance Program, Frederick, MD 21701 USA.
[Phillip, Pretty S.; Rizvi, Tahir A.] United Arab Emirates Univ, Fac Med & Hlth Sci, Dept Microbiol & Immunol, Al Ain, U Arab Emirates.
RP Lever, AML (reprint author), Univ Cambridge, Addenbrookes Hosp, Dept Med, Box 157,Level 5,Hills Rd, Cambridge CB2 0QQ, England.
EM amll1@medschl.cam.ac.uk
FU National Cancer institute, National Institutes of Health; Wellcome Trust
[078007/Z/05/Z]; Biomedical Research Centre [RG52162]; Medical Research
Council
FX The Intramural Research Program of the National Cancer institute,
National Institutes of Health (S.F.J.LeG.); the Wellcome Trust
(078007/Z/05/Z to A. M. L. L. and T. A. R); and the Biomedical Research
Centre (RG52162 to A. M. L. L). Funding for open access charge: Medical
Research Council.
NR 50
TC 16
Z9 16
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 AUG
PY 2011
VL 39
IS 15
BP 6692
EP 6704
DI 10.1093/nar/gkr252
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 815UQ
UT WOS:000294555800039
PM 21546549
ER
PT J
AU Holighaus, Y
Mustafa, T
Eiden, LE
AF Holighaus, Yvonne
Mustafa, Tomris
Eiden, Lee E.
TI PAC1hop, null and hip receptors mediate differential signaling through
cyclic AMP and calcium leading to splice variant-specific gene induction
in neural cells
SO PEPTIDES
LA English
DT Article
DE PACAP; PAC1 receptor; cAMP; Calcium; Gene induction; Nervous system
ID CYCLASE-ACTIVATING POLYPEPTIDE; VASOACTIVE-INTESTINAL-PEPTIDE; NERVE
GROWTH-FACTOR; CEREBELLAR GRANULE NEURONS; ADRENAL CHROMAFFIN CELLS;
IN-SITU HYBRIDIZATION; GLIOMA HYBRID-CELLS; PROTEIN-KINASE-A;
ADENYLATE-CYCLASE; PACAP RECEPTOR
AB Pituitary adenylate cyclase-activating polypeptide (PACAP)-mediated of its G protein-coupled receptor PAC1 results in activation of the two G proteins Gs and Gq to alter second messenger generation and gene transcription in the nervous system, important for homeostatic responses to stress and injury. Heterologous expression of the three major splice variants of the rat PAC1 receptor, PAC1hop, null and hip, in neural NG108-15 cells conferred PACAP-mediated intracellular cAMP generation, while elevation of [Ca2(+)](i) occurred only in PAC1hop-, and to a lesser extent in PAC1null-expressing cells. Induction of vasoactive intestinal polypeptide (VIP) and stanniocalcin 1 (STC1), two genes potentially involved in PACAP's homeostatic responses, was examined as a function of the expressed PAC1 variant. VIP induction was greatest in PAC1hop-expressing cells, suggesting that a maximal transcriptional response requires combinatorial signaling through both cAMP and Ca(2+). STC1 induction was similar for all three receptor splice variants and was mimicked by the adenylate cyclase activator forskolin, indicating that cAMP elevation is sufficient to induce STC1. The degree of activation of two different second messenger pathways appears to determine the transcriptional response, suggesting that cellular responses to stressors are fine-tuned through differential receptor isoform expression. Signaling to the VIP gene proceeded through cAMP and protein kinase A (PKA) in these cells, independently of the MAP kinase ERK1/2. STC1 gene induction by PACAP was dependent on cAMP and ERK1/2, independently of PKA. Differential gene induction via different cAMP dependent signaling pathways potentially provides further targets for the design of treatments for stress-associated disorders. Published by Elsevier Inc.
C1 [Holighaus, Yvonne; Mustafa, Tomris; Eiden, Lee E.] NIMH, Sect Mol Neurosci, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA.
RP Eiden, LE (reprint author), NIMH, Sect Mol Neurosci, Lab Cellular & Mol Regulat, Bldg 49,Room 5A-38,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM eidenl@mail.nih.gov
OI Eiden, Lee/0000-0001-7524-944X
FU NIMH [Z01 MH002386-22]
FX We thank Dr. Laurent Journot for sharing their pRK8-PAC1 vectors, James
Walsh for assistance in the subcloning of the PAC1 receptor variants,
James Nagle and Debbie Kauffman (DNA Sequencing Facility, NINDS,
National Institutes of Health) for carrying out sequencing of all DNA
samples, Dr. Maribeth V. Eiden and members of her lab (NIMH, National
Institutes of Health) for assistance in producing viral particles and
Prof. E. Weihe (Philipps-University, Marburg, Germany) for advice and
consultation in preparation of this report. This work was supported by
NIMH Intramural Research Program Project Z01 MH002386-22.
NR 69
TC 13
Z9 13
U1 1
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-9781
J9 PEPTIDES
JI Peptides
PD AUG
PY 2011
VL 32
IS 8
BP 1647
EP 1655
DI 10.1016/j.peptides.2011.06.004
PG 9
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism;
Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism;
Pharmacology & Pharmacy
GA 816BD
UT WOS:000294572800012
PM 21693142
ER
EF