FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Liebman, MN
   Marincola, FM
AF Liebman, Michael N.
   Marincola, Francesco M.
TI Expanding the perspective of translational medicine: the value of
   observational data
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Editorial Material
ID CORONARY-HEART-DISEASE; HEALTH; WOMEN
AB In 2003, the Journal of Translational Medicine was launched to foster the publication of high quality research in both "bench-to-bedside" as well as ex vivo human observation. In spite of the success of several large-scale observational studies, e.g. Framingham Heart Study, the opportunity to expand upon the ex vivo human observation has remained limited within the field of translational medicine. We believe that this presents a significant opportunity that merits consideration in both the planning and analysis of large scale observational studies and can contribute greatly to expanding our approaches in translational medicine
C1 [Liebman, Michael N.] Strateg Med Inc, Kennett Sq, PA 19348 USA.
   [Marincola, Francesco M.] NIH, Bethesda, MD 20892 USA.
RP Liebman, MN (reprint author), Strateg Med Inc, 231 Deepdale Dr, Kennett Sq, PA 19348 USA.
EM m.liebman@strategicmedicine.com
NR 7
TC 5
Z9 5
U1 0
U2 2
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 MAR 27
PY 2012
VL 10
AR 61
DI 10.1186/1479-5876-10-61
PG 3
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 921RB
UT WOS:000302493700001
PM 22452969
ER

PT J
AU Jamal, SM
   Strait, J
   Meirelles, O
   Ding, J
   Mehring, LD
   Sperry, B
   Saadi, A
   Singh, T
   Nayda, J
   Karikkineth, A
   Tarasov, K
   Orru, M
   Van der Harst, P
   Verweij, N
   Dei, M
   Cucca, F
   Schlessinger, D
   Lakatta, E
AF Jamal, Sameer M.
   Strait, James
   Meirelles, Osorio
   Ding, Jun
   Mehring, Lindsay D.
   Sperry, Brett
   Saadi, Abdulghani
   Singh, Tania
   Nayda, John
   Karikkineth, Ajoy
   Tarasov, Kirill
   Orru, Marco
   Van der Harst, Pim
   Verweij, Niek
   Dei, Mariano
   Cucca, Francesco
   Schlessinger, David
   Lakatta, Edward
TI EARLY REPOLARIZATION PATTERN: CLINICAL CORRELATES OF SPECIFIC
   ELECTROCARDIOGRAPHIC SUBTYPES AND GENOME WIDE ASSOCIATION STUDY OF A
   SARDINIAN POPULATION
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 61st Annual Scientific Session and Expo of the
   American-College-of-Cardiology (ACC)
CY MAR 24-27, 2012
CL Chicago, IL
SP Amer Coll Cardiol (ACC)
C1 NIA, Baltimore, MD 21224 USA.
   Georgetown Univ, Washington Hosp Ctr, Washington, DC USA.
RI Verweij, Niek/A-4499-2017
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 27
PY 2012
VL 59
IS 13
SU S
BP E719
EP E719
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 919LB
UT WOS:000302326700720
ER

PT J
AU Koh, KK
   Quon, M
   Choi, H
AF Koh, Kwang K.
   Quon, Michael
   Choi, Hanul
TI SIGNIFICANT DIFFERENTIAL EFFECTS OF OMEGA-3 FATTY ACIDS AND FENOFIBRATE
   IN PATIENTS WITH HYPERTRIGLYCERIDEMIA
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 61st Annual Scientific Session and Expo of the
   American-College-of-Cardiology (ACC)
CY MAR 24-27, 2012
CL Chicago, IL
SP Amer Coll Cardiol (ACC)
C1 Gachon Univ, Gil Med Ctr, Inchon, South Korea.
   NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 27
PY 2012
VL 59
IS 13
SU S
BP E1694
EP E1694
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 919LB
UT WOS:000302326701805
ER

PT J
AU Strait, JB
   Jamal, S
   Saadi, A
   Sperry, B
   Mehring, L
   Singh, T
   Nayda, J
   Tanaka, T
   David, M
   Canepa, M
   Moni, M
   Ferrucci, L
   Lakatta, E
AF Strait, James B.
   Jamal, Sameer
   Saadi, Abdulghani
   Sperry, Brett
   Mehring, Lindsay
   Singh, Tania
   Nayda, John
   Tanaka, Toshiko
   David, Melissa
   Canepa, Marco
   Moni, Monika
   Ferrucci, Luigi
   Lakatta, Edward
TI ECHOCARDIOGRAPHIC AND CLINICAL CORRELATES OF SPECIFIC EARLY
   REPOLARIZATION SUBTYPES ON ELECTROCARDIOGRAM
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 61st Annual Scientific Session and Expo of the
   American-College-of-Cardiology (ACC)
CY MAR 24-27, 2012
CL Chicago, IL
SP Amer Coll Cardiol (ACC)
C1 NIA, Baltimore, MD 21224 USA.
   Georgetown Washington Hosp Ctr, Washington, DC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 27
PY 2012
VL 59
IS 13
SU S
BP E658
EP E658
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 919LB
UT WOS:000302326700660
ER

PT J
AU Vargas, JD
   Chen, MY
   Arai, AE
   Mullikin, JC
   Bluemke, DA
   Biesecker, LG
AF Vargas, Jose D.
   Chen, Marcus Y.
   Arai, Andrew E.
   Mullikin, James C.
   Bluemke, David A.
   Biesecker, Leslie G.
TI RARE CODING GENETIC VARIANTS AND CORONARY ARTERY CALCIUM IN THE
   CLINSEQTM STUDY
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 61st Annual Scientific Session and Expo of the
   American-College-of-Cardiology (ACC)
CY MAR 24-27, 2012
CL Chicago, IL
SP Amer Coll Cardiol (ACC)
C1 NIH, Bethesda, MD 20892 USA.
   Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 27
PY 2012
VL 59
IS 13
SU S
BP E1187
EP E1187
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 919LB
UT WOS:000302326701298
ER

PT J
AU Horkay, F
   Basser, PJ
   Hecht, AM
   Geissler, E
AF Horkay, Ferenc
   Basser, Peter J.
   Hecht, Anne-Marie
   Geissler, Erik
TI Chondroitin Sulfate in Solution: Effects of Mono- and Divalent Salts
SO MACROMOLECULES
LA English
DT Article
ID HUMAN ARTICULAR-CARTILAGE; ANGLE NEUTRON-SCATTERING;
   AGE-RELATED-CHANGES; SPINAL-CORD-INJURY; POLYELECTROLYTE SOLUTIONS;
   POLY(VINYL ALCOHOL); LIGHT-SCATTERING; HYDROGELS; ABC;
   GLYCOSAMINOGLYCANS
AB Chondroitin sulfate (CS) is a linear sulfated polysaccharide found in cartilage and other tissues in the body. Small-angle neutron scattering (SANS) and dynamic light scattering (DLS) measurements are made on semidilute CS solutions to determine ion-induced changes in the local order of the CS chains and in their dynamic properties. In salt-free CS solutions SANS detects the correlation peak due to local ordering between adjacent chains in which the characteristic interchain distance is d approximate to 57 angstrom. In both monovalent and divalent salts (NaCl and CaCl2) aligned linear regions are distinguishable, corresponding to distance scales ranging from the length of the monomer unit (8 angstrom) to about 1000 angstrom. With increasing calcium ion concentration, the scattering intensity increases. Even in the presence of 200 mM CaCl2, however, neither phase separation nor cross-linking occurs. DLS in the CS solutions reveals two characteristic relaxation modes, the fast mode corresponding to the thermal concentration fluctuations. The collective diffusion coefficient D decreases with increasing calcium ion concentration and exhibits a power law function of the single variable c/J, where c is the CS concentration and J is the ionic strength of the salt in the solution. This result implies that the effect of the sodium and calcium ions on the dynamic properties of CS solutions is fully accounted for by the ionic strength.
C1 [Horkay, Ferenc; Basser, Peter J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Tissue Biophys & Biomimet, Program Pediat Imaging & Tissue Sci, NIH, Bethesda, MD 20892 USA.
   [Hecht, Anne-Marie; Geissler, Erik] Univ Grenoble 1, CNRS, UMR 5588, Lab Interdisciplinaire Phys, F-38402 St Martin Dheres, France.
RP Horkay, F (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Tissue Biophys & Biomimet, Program Pediat Imaging & Tissue Sci, NIH, 13 South Dr, Bethesda, MD 20892 USA.
EM horkay@helix.nih.gov
RI Basser, Peter/H-5477-2011
FU NICHD, NIH
FX This research was supported by the Intramural Research Program of the
   NICHD, NIH. We acknowledge the support of the National Institute of
   Standards and Technology, U.S. Department of Commerce, in providing the
   neutron research facilities used in this work. This work utilized
   facilities supported in part by the National Science Foundation under
   Agreement DMR-0944772. We gratefully acknowledge the help and
   consultation of Dr. Boualem Hammouda (NIST) with the SANS experiment.
NR 50
TC 11
Z9 11
U1 2
U2 27
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0024-9297
J9 MACROMOLECULES
JI Macromolecules
PD MAR 27
PY 2012
VL 45
IS 6
BP 2882
EP 2890
DI 10.1021/ma202693s
PG 9
WC Polymer Science
SC Polymer Science
GA 914JT
UT WOS:000301946600029
PM 23814316
ER

PT J
AU Levy, Y
   Thiebaut, R
   Gougeon, ML
   Molina, JM
   Weiss, L
   Girard, PM
   Venet, A
   Morlat, P
   Poirier, B
   Lascaux, AS
   Boucherie, C
   Sereni, D
   Rouzioux, C
   Viard, JP
   Lane, C
   Delfraissy, JF
   Sereti, I
   Chene, G
AF Levy, Yves
   Thiebaut, Rodolphe
   Gougeon, Marie-Lise
   Molina, Jean-Michel
   Weiss, Laurence
   Girard, Pierre-Marie
   Venet, Alain
   Morlat, Philippe
   Poirier, Beatrice
   Lascaux, Anne-Sophie
   Boucherie, Celine
   Sereni, Daniel
   Rouzioux, Christine
   Viard, Jean-Paul
   Lane, Cliff
   Delfraissy, Jean-Francois
   Sereti, Irini
   Chene, Genevieve
CA ILIADE Study Grp
TI Effect of intermittent interleukin-2 therapy on CD4(+) T-cell counts
   following antiretroviral cessation in patients with HIV
SO AIDS
LA English
DT Article
DE antiretroviral therapy interruption; HIV; interleukin-2
ID RANDOMIZED CONTROLLED-TRIAL; IN-VIVO EXPANSION; INFECTED PATIENTS;
   TREATMENT INTERRUPTION; GENERAL-POPULATION; IL-2 THERAPY; SUPPRESSION;
   CELLS/MM(3); ACTIVATION; INDUCTION
AB Background: Interleukin (IL)-2 therapy impacts T-cell homeostasis. Whether IL-2 expanded CD4(+) T cells may persist following viral rebound has not been fully investigated.
   Methods: Patients with CD4(+) T cells 500/mu l or more and HIV RNA less than 50 copies/ml were randomized to continue antiretroviral therapy (ART) either alone (n = 67) or combined with three IL-2 cycles (n = 81; 6 million units) twice daily for 5 days at weeks 0, 8, and 16 before stopping ART (week 24). Patients were followed up to 168 weeks.
   Results: At week 24, median CD4(+) T-cell counts were 1198 and 703 cells/mu l in the IL-2 and control groups, respectively (P<0.001). At week 72, 27% (IL-2 group) and 45% (control group; P = 0.03) of patients were in failure (defined as no interruption of ART at week 24, CD4 drop below 350 cells/ml or ART resumption). After week 24, a biphasic decline (before and after week 32) of CD4 was noted =106 and =7 cells/mu l per month in controls and = 234 and =17 in IL-2 group (all P < 0.0001). At week 96, IL-2-expanded CD4(+)CD25(+) T cells remained higher than in the control group (26 vs. 16%, P = 0.006).
   Conclusion: In IL-2-treated patients, CD4(+)CD25(+) T cells persisting despite viral replication allow a longer period of ART interruption. (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Levy, Yves; Lascaux, Anne-Sophie] Hop Henri Mondor, AP HP, Serv Immunol Clin, Grp Henri Mondor Albert Chenevier, F-94010 Creteil, France.
   [Levy, Yves] INSERM, Unite U955, F-75654 Paris 13, France.
   [Levy, Yves] Univ Paris Est, Fac Med, UMR S 955, Paris, France.
   [Thiebaut, Rodolphe; Morlat, Philippe; Boucherie, Celine; Chene, Genevieve] INSERM, U897, F-75654 Paris 13, France.
   [Thiebaut, Rodolphe; Chene, Genevieve] Univ Bordeaux Segalen, ISPED, Bordeaux, France.
   [Thiebaut, Rodolphe; Morlat, Philippe; Chene, Genevieve] CHU Bordeaux, Bordeaux, France.
   [Gougeon, Marie-Lise; Poirier, Beatrice] Inst Pasteur, Antiviral Immun Biotherapy & Vaccine Unit, Paris, France.
   [Molina, Jean-Michel; Sereni, Daniel] St Louis Hosp, AP HP, St Louis, France.
   [Weiss, Laurence] Hop Europeen Georges Pompidou, AP HP, Paris, France.
   [Girard, Pierre-Marie] St Antoine Hosp, AP HP, Paris, France.
   [Venet, Alain] INSERM, U1012, Le Kremlin Bicetre, France.
   [Rouzioux, Christine] Univ Paris 05, Hop Necker, AP HP, Paris, France.
   [Viard, Jean-Paul] Hop Hotel Dieu, AP HP, Paris, France.
   [Lane, Cliff; Sereti, Irini] NIH, Bethesda, MD USA.
   [Delfraissy, Jean-Francois] Hop Kremlin Bicetre, AP HP, Le Kremlin Bicetre, France.
RP Levy, Y (reprint author), Hop Henri Mondor, AP HP, Serv Immunol Clin, Grp Henri Mondor Albert Chenevier, 51 Ave Marechal de Lattre de Tassigny, F-94010 Creteil, France.
EM yves.levy@hmn.aphp.fr
RI chene, genevieve/H-8665-2014
FU French National Agency for Research on AIDS and Viral Hepatitis (ANRS)
   [118]; NIAID/NIH [NIH 04-I-0018 trial]
FX This study was supported by the French National Agency for Research on
   AIDS and Viral Hepatitis (ANRS, Trial No. 118) and the Intramural
   Research Program of NIAID/NIH (NIH 04-I-0018 trial).
NR 31
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U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD MAR 27
PY 2012
VL 26
IS 6
BP 711
EP 720
DI 10.1097/QAD.0b013e3283519214
PG 10
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 914UA
UT WOS:000301976900007
PM 22301410
ER

PT J
AU DeRose, EF
   Perera, L
   Murray, MS
   Kunkel, TA
   London, RE
AF DeRose, Eugene F.
   Perera, Lalith
   Murray, Michael S.
   Kunkel, Thomas A.
   London, Robert E.
TI Solution Structure of the Dickerson DNA Dodecamer Containing a Single
   Ribonucleotide
SO BIOCHEMISTRY
LA English
DT Article
ID EXCHANGEABLE PROTON RESONANCES; CRYSTAL-STRUCTURE; B-DNA; DIPOLAR
   COUPLINGS; OKAZAKI FRAGMENT; TOPOISOMERASE-I; NMR STRUCTURE; A-DNA; RNA;
   DUPLEX
AB Ribonucleotides are frequently incorporated into DNA during replication. They are recognized and processed by several cellular enzymes, and their continued presence in the yeast nuclear genome results in replicative stress and genome instability. Thus, it is important to understand the effects of isolated ribonucleotide incorporation on DNA structure. With this goal in mind, we describe the nuclear magnetic resonance structure of the self-complementary Dickerson dodecamer sequence [d(CGC)rGd(AATTCGCG)](2) containing two symmetrically positioned riboguanosines. The absence of an observable H-1-H-2 scalar coupling interaction indicates a C3'-endo conformation for the ribose. Longer-range structural perturbations resulting from the presence of the ribonucleotide are limited to the adjacent and transhelical nucleotides, while the global B-form DNA structure is maintained. Because crystallographic studies have indicated that isolated ribonucleotides promote global B -> A transitions, we also performed molecular modeling analyses to evaluate the structural consequences of higher ribonucleotide substitution levels. Increasing the ribonucleotide content increased the minor groove width toward values more similar to that of A-DNA, but even 50% ribonucleotide substitution did not fully convert the B-DNA to A-DNA. Comparing our structure with the structure of an RNase H2-bound DNA supports the conclusion that, as with other DNA protein complexes, the DNA conformation is strongly influenced by the interaction with the protein.
C1 [DeRose, Eugene F.; Perera, Lalith; Murray, Michael S.; Kunkel, Thomas A.; London, Robert E.] NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
   [Murray, Michael S.; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP London, RE (reprint author), NIEHS, MR Lab Struct Biol 01, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM london@niehs.nih.gov
RI perera, Lalith/B-6879-2012
OI perera, Lalith/0000-0003-0823-1631
FU National Institute of Environmental Health Sciences (NIEHS)
   [Z01-ES050111, Z01 ES065070, HHSN273200700046U]
FX This research was supported by Grant Z01-ES050111 to R.E.L. and Grant
   Z01 ES065070 to T.A.K., both in the Intramural Research Program of the
   National Institute of Environmental Health Sciences (NIEHS). E.F.D. is
   supported by the NIEHS under Delivery Order HHSN273200700046U.
NR 53
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U1 1
U2 26
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD MAR 27
PY 2012
VL 51
IS 12
BP 2407
EP 2416
DI 10.1021/bi201710q
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 914JQ
UT WOS:000301946300005
PM 22390730
ER

PT J
AU Tsurupa, G
   Pechik, I
   Litvinov, RI
   Hantgan, RR
   Tjandra, N
   Weisel, JW
   Medved, L
AF Tsurupa, Galina
   Pechik, Igor
   Litvinov, Rustem I.
   Hantgan, Roy R.
   Tjandra, Nico
   Weisel, John W.
   Medved, Leonid
TI On the Mechanism of alpha C Polymer Formation in Fibrin
SO BIOCHEMISTRY
LA English
DT Article
ID AMINO-ACID-SEQUENCE; FIBRONECTIN-BINDING; BOVINE FIBRINOGEN; STRUCTURAL
   ORGANIZATION; ELECTRON-MICROSCOPY; DOMAIN FRAGMENT; CROSS-LINKING;
   FACTOR-XIIIA; SITES; CHAIN
AB Our previous studies revealed that the fibrinogen alpha C-domains undergo conformational changes and adopt a physiologically active conformation upon their self-association into alpha C polymers in fibrin. In the present study, we analyzed the mechanism of alpha C polymer formation and tested our hypothesis that self-association of the alpha C-domains occurs through the interaction between their N-terminal subdomains and may include beta-hairpin swapping. Our binding experiments performed by size-exclusion chromatography and optical trap-based force spectroscopy revealed that the alpha C-domains self-associate exclusively through their N-terminal subdomains, while their C-terminal subdomains were found to interact with the alpha C-connectors that tether the alpha C-domains to the bulk of the molecule. This interaction should reinforce the structure of alpha C polymers and provide the proper orientation of their reactive residues for efficient cross-linking by factor XIIIa. Molecular modeling of self-association of the N-terminal subdomains confirmed that the hypothesized beta-hairpin swapping does not impose any steric hindrance. To "freeze" the conformation of the N-terminal subdomain and prevent the hypothesized beta-hairpin swapping, we introduced by site-directed mutagenesis an extra disulfide bond between two beta-hairpins of the bovine A alpha 406-483 fragment corresponding to this subdomain. The experiments performed by circular dichroism revealed that A alpha 406-483 mutant containing Lys429Cys/Thr463Cys mutations preserved its beta-sheet structure. However, in contrast to wild-type A alpha 406-483, this mutant had lower tendency for oligomerization, and its structure was not stabilized upon oligomerization, in agreement with the above hypothesis. On the basis of the results obtained and our previous findings, we propose a model of fibrin alpha C polymer structure and molecular mechanism of assembly.
C1 [Tsurupa, Galina; Medved, Leonid] Univ Maryland, Ctr Vasc & Inflammatory Dis, Sch Med, Baltimore, MD 21201 USA.
   [Tsurupa, Galina; Medved, Leonid] Univ Maryland, Dept Biochem, Sch Med, Baltimore, MD 21201 USA.
   [Pechik, Igor] Walter Reed Army Inst Res, Silver Spring, MD 20910 USA.
   [Litvinov, Rustem I.; Weisel, John W.] Univ Penn, Dept Cell & Dev Biol, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Hantgan, Roy R.] Wake Forest Univ, Bowman Gray Sch Med, Dept Biochem, Winston Salem, NC 27157 USA.
   [Tjandra, Nico] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
RP Medved, L (reprint author), Univ Maryland, Ctr Vasc & Inflammatory Dis, Sch Med, Baltimore, MD 21201 USA.
EM lmedved@som.umaryland.edu
RI Litvinov, Rustem/E-5291-2011
OI Litvinov, Rustem/0000-0003-0643-1496
FU National Institutes of Health [HL056051, HL030954, HL090774]; National
   Heart Lung, and Blood Institute
FX This work was supported by National Institutes of Health Grants HL056051
   to L.M., HL030954 and HL090774 to J.W.W., and by the Intramural Research
   Program of the National Heart Lung, and Blood Institute to N.T.
NR 54
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U1 0
U2 16
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD MAR 27
PY 2012
VL 51
IS 12
BP 2526
EP 2538
DI 10.1021/bi2017848
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 914JQ
UT WOS:000301946300017
PM 22397628
ER

PT J
AU Trabert, B
   Graubard, BI
   Erickson, RL
   McGlynn, KA
AF Trabert, B.
   Graubard, B. I.
   Erickson, R. L.
   McGlynn, K. A.
TI Childhood infections, orchitis and testicular germ cell tumours: a
   report from the STEED study and a meta-analysis of existing data
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE testicular germ cell tumours; childhood infections; mumps; orchitis;
   case-control
ID RISK-FACTORS; YOUNG MEN; CANCER; TESTIS; EPIDEMIOLOGY; ETIOLOGY
AB BACKGROUND: Similarities between the age-specific incidence pattern of testicular germ cell tumours (TGCTs) and the age-specific incidence pattern of cancers of viral origin prompted us to evaluate the relationship between common infections occurring during childhood or young adult life and TGCT using existing data from the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) case-control study.
   METHODS: TGCT cases diagnosed between 2002 and 2005 (n = 767) were matched on age, race and serum draw date to at least one control (n = 929).
   RESULTS: None of the infections evaluated were associated with TGCT risk. Further, a meta-analysis of mumps and mumps orchitis or orchitis infection did not support an association with TGCT (mumps pooled odds ratio (OR): 1.03, 95% confidence interval (CI): 0.89-1.20; mumps orchitis or orchitis pooled OR: 1.80, 95% CI: 0.74-4.42).
   CONCLUSION: Based on our evaluation of childhood and early life infections and meta-analyses of mumps and mumps orchitis and/or orchitis, TGCT does not appear to be associated with common childhood infections.
C1 [Trabert, B.; McGlynn, K. A.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA.
   [Graubard, B. I.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA.
   [Erickson, R. L.] Walter Reed Army Inst Res, Silver Spring, MD 20910 USA.
RP Trabert, B (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,Suite 550, Rockville, MD 20852 USA.
EM trabertbl@mail.nih.gov
RI Trabert, Britton/F-8051-2015
FU National Cancer Institute
FX This work was supported by the Intramural Research Program of the
   National Cancer Institute.
NR 21
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U1 0
U2 3
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 MAR 27
PY 2012
VL 106
IS 7
BP 1331
EP 1334
DI 10.1038/bjc.2012.45
PG 4
WC Oncology
SC Oncology
GA 916VG
UT WOS:000302130700012
PM 22343618
ER

PT J
AU Fu, YP
   Kohaar, I
   Rothman, N
   Earl, J
   Figueroa, JD
   Ye, Y
   Malats, N
   Tang, W
   Liu, L
   Garcia-Closas, M
   Muchmore, B
   Chatterjee, N
   Tarway, M
   Kogevinas, M
   Porter-Gill, P
   Baris, D
   Mumy, A
   Albanes, D
   Purdue, MP
   Hutchinson, A
   Carrato, A
   Tardon, A
   Serra, C
   Garcia-Closas, R
   Lloreta, J
   Johnson, A
   Schwenn, M
   Karagas, MR
   Schned, A
   Diver, WR
   Gapstur, SM
   Thun, MJ
   Virtamo, J
   Chanock, SJ
   Fraumeni, JF
   Silverman, DT
   Wu, XF
   Real, FX
   Prokunina-Olsson, L
AF Fu, Yi-Ping
   Kohaar, Indu
   Rothman, Nathaniel
   Earl, Julie
   Figueroa, Jonine D.
   Ye, Yuanqing
   Malats, Nuria
   Tang, Wei
   Liu, Luyang
   Garcia-Closas, Montserrat
   Muchmore, Brian
   Chatterjee, Nilanjan
   Tarway, McAnthony
   Kogevinas, Manolis
   Porter-Gill, Patricia
   Baris, Dalsu
   Mumy, Adam
   Albanes, Demetrius
   Purdue, Mark P.
   Hutchinson, Amy
   Carrato, Alfredo
   Tardon, Adonina
   Serra, Consol
   Garcia-Closas, Reina
   Lloreta, Josep
   Johnson, Alison
   Schwenn, Molly
   Karagas, Margaret R.
   Schned, Alan
   Diver, W. Ryan
   Gapstur, Susan M.
   Thun, Michael J.
   Virtamo, Jarmo
   Chanock, Stephen J.
   Fraumeni, Joseph F., Jr.
   Silverman, Debra T.
   Wu, Xifeng
   Real, Francisco X.
   Prokunina-Olsson, Ludmila
TI Common genetic variants in the PSCA gene influence gene expression and
   bladder cancer risk
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID STEM-CELL ANTIGEN; GENOME-WIDE ASSOCIATION; CONFERS SUSCEPTIBILITY;
   PROSTATE-CANCER; IDENTIFICATION; ENHANCERS; SMOKING
AB Genome-wide association studies have identified a SNP, rs2294008, on 8q24.3 within the prostate stem cell antigen (PSCA) gene, as a risk factor for bladder cancer. To fine-map this region, we imputed 642 SNPs within 100 Kb of rs2294008 in addition to 33 markers genotyped in one of the reported genome-wide association study in 8,652 subjects. A multivariable logistic regression model adjusted for rs2294008 revealed a unique signal, rs2978974 (r(2) = 0.02, D' = 0.19 with rs2294008). In the combined analysis of 5,393 cases and 7,324 controls, we detected a per-allele odds ratio (OR) = 1.11 [95% confidence interval (CI) = 1.06-1.17, P = 5.8 x 10(-5)] for rs2294008 and OR = 1.07 (95% CI = 1.02-1.13, P= 9.7 x 10(-3)) for rs2978974. The effect was stronger in carriers of both risk variants (OR = 1.24, 95% CI = 1.08-1.41, P = 1.8 x 10(-3)) and there was a significant multiplicative interaction (P = 0.035) between these two SNPs, which requires replication in future studies. The T risk allele of rs2294008 was associated with increased PSCA mRNA expression in two sets of bladder tumor samples (n = 36, P = 0.0007 and n = 34, P = 0.0054) and in normal bladder samples (n = 35, P = 0.0155), but rs2978974 was not associated with PSCA expression. SNP rs2978974 is located 10 Kb upstream of rs2294008, within an alternative untranslated first exon of PSCA. The non-risk allele G of rs2978974 showed strong interaction with nuclear proteins from five cell lines tested, implying a regulatory function. In conclusion, a joint effect of two PSCA SNPs, rs2294008 and rs2978974, suggests that both variants may be important for bladder cancer susceptibility, possibly through different mechanisms that influence the control of mRNA expression and interaction with regulatory factors.
C1 [Rothman, Nathaniel; Figueroa, Jonine D.; Garcia-Closas, Montserrat; Chatterjee, Nilanjan; Baris, Dalsu; Albanes, Demetrius; Purdue, Mark P.; Fraumeni, Joseph F., Jr.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
   [Fu, Yi-Ping; Kohaar, Indu; Tang, Wei; Liu, Luyang; Muchmore, Brian; Tarway, McAnthony; Porter-Gill, Patricia; Mumy, Adam; Chanock, Stephen J.; Prokunina-Olsson, Ludmila] NCI, Lab Translat Gen, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
   [Earl, Julie; Real, Francisco X.] Ctr Nacl Invest Oncol, Epithelial Carcinogenesis Grp, Mol Pathol Programme, Madrid 28029, Spain.
   [Ye, Yuanqing] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
   [Malats, Nuria] Spanish Natl Canc Res Ctr, Genet & Mol Epidemiol Grp, Madrid 28029, Spain.
   [Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, London SW7 3RP, England.
   [Kogevinas, Manolis] Ctr Res Environm Epidemiol, Barcelona 08003, Spain.
   [Kogevinas, Manolis; Tardon, Adonina] Municipal Inst Med Res, Barcelona 08003, Spain.
   [Kogevinas, Manolis] Ctr Invest Biomed Red Epidemiol & Salud Publ, Barcelona 08003, Spain.
   [Kogevinas, Manolis] Natl Sch Publ Hlth, Athens 11521, Greece.
   [Hutchinson, Amy] NCI, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21702 USA.
   [Carrato, Alfredo] Ramon & Cajal Univ Hosp, Madrid 28034, Spain.
   [Tardon, Adonina] Univ Oviedo, Inst Univ Oncol, Oviedo 33003, Spain.
   [Serra, Consol; Real, Francisco X.] Univ Pompeu Fabra, Dept Ciencies Expt Salut, Barcelona 08003, Spain.
   [Lloreta, Josep] Univ Pompeu Fabra, Hosp del Mar, Inst Municipa Invest Med, Barcelona 08003, Spain.
   [Garcia-Closas, Reina] Hosp Univ Canarias, Unidad Invest, San Cristobal la Laguna 38320, Spain.
   [Johnson, Alison] Vermont Canc Registry, Burlington, VT 05401 USA.
   [Schwenn, Molly] Maine Canc Registry, Augusta, ME 04333 USA.
   [Karagas, Margaret R.; Schned, Alan] Dartmouth Med Sch, Hanover, NH 03755 USA.
   [Diver, W. Ryan; Gapstur, Susan M.; Thun, Michael J.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30303 USA.
   [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki 00271, Finland.
RP Fraumeni, JF (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
EM fraumeni@nih.gov; prokuninal@mail.nih.gov
RI Albanes, Demetrius/B-9749-2015; Tang, Wei/H-7103-2013; Serra,
   C/E-6879-2014; Garcia-Closas, Montserrat /F-3871-2015; Malats,
   Nuria/H-7041-2015; Purdue, Mark/C-9228-2016; Kogevinas,
   Manolis/C-3918-2017; Lloreta, J/I-2112-2014
OI Tang, Wei/0000-0002-7089-4391; Serra, C/0000-0001-8337-8356;
   Garcia-Closas, Montserrat /0000-0003-1033-2650; Malats,
   Nuria/0000-0003-2538-3784; Purdue, Mark/0000-0003-1177-3108;
   Prokunina-Olsson, Ludmila/0000-0002-9622-2091; Lloreta,
   J/0000-0003-1644-9470
FU Information Management Services; Institut Municipal d'Investigacio
   Medica; Westat, Inc.; Marques de Valdecilla University Hospital;
   Hospital Ciudad de Coria; National Cancer Institute, National Institutes
   of Health [HHSN261200800001E]; US Public Health Service from the
   National Cancer Institute, Department of Health and Human Services
   [N01-CN-45165, N01-RC-45035, N01-RC-37004]
FX We thank the following for their support of this project: Leslie
   Carroll, Jane Wang, Anne Taylor, and Kirk Snyder (Information Management
   Services); Gemma Castano-Vinyals, Fernando Fernandez, Maria Sala, and
   Montserrat Tora (Institut Municipal d'Investigacio Medica); Paul
   Hurwitz, Charles Lawrence, Anna McIntosh, and Robert Saal (Westat,
   Inc.); Marta Lopez-Brea and Fernando Rivera (Marques de Valdecilla
   University Hospital); and Angeles Panadero (Hospital Ciudad de Coria).
   This project has been funded in part by the Intramural Research Program
   of the National Cancer Institute, National Institutes of Health, under
   Contract HHSN261200800001E. Additionally, this research was supported by
   US Public Health Service Contracts N01-CN-45165, N01-RC-45035, and
   N01-RC-37004 from the National Cancer Institute, Department of Health
   and Human Services. The content of this publication does not necessarily
   reflect the views or policies of the Department of Health and Human
   Services, nor does mention of trade names, commercial products, or
   organizations imply endorsement by the U.S. Government. The funders had
   no role in study design, data collection and analysis, decision to
   publish, or preparation of the manuscript. Additional funding
   information is provided in SI Materials and Methods.
NR 40
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U1 2
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 MAR 27
PY 2012
VL 109
IS 13
BP 4974
EP 4979
DI 10.1073/pnas.1202189109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 917HT
UT WOS:000302164200055
PM 22416122
ER

PT J
AU Chianini, F
   Fernandez-Borges, N
   Vidal, E
   Gibbard, L
   Pintadoe, B
   de Castro, J
   Priola, SA
   Hamilton, S
   Eaton, SL
   Finlayson, J
   Pang, Y
   Steele, P
   Reid, HW
   Dagleish, MP
   Castilla, J
AF Chianini, Francesca
   Fernandez-Borges, Natalia
   Vidal, Enric
   Gibbard, Louise
   Pintadoe, Belen
   de Castro, Jorge
   Priola, Suzette A.
   Hamilton, Scott
   Eaton, Samantha L.
   Finlayson, Jeanie
   Pang, Yvonne
   Steele, Philip
   Reid, Hugh W.
   Dagleish, Mark P.
   Castilla, Joaquin
TI Rabbits are not resistant to prion infection
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE in vitro replication; scrapie; transmissible spongiform encephalopathy
ID MISFOLDING CYCLIC AMPLIFICATION; IN-VITRO; SPONGIFORM ENCEPHALOPATHY;
   SPECIES-BARRIER; PROTEIN; SCRAPIE; PROPAGATION; REPLICATION;
   TRANSMISSION; GENERATION
AB The ability of prions to infect some species and not others is determined by the transmission barrier. This unexplained phenomenon has led to the belief that certain species were not susceptible to transmissible spongiform encephalopathies (TSEs) and therefore represented negligible risk to human health if consumed. Using the protein misfolding cyclic amplification (PMCA) technique, we were able to overcome the species barrier in rabbits, which have been classified as TSE resistant for four decades. Rabbit brain homogenate, either unseeded or seeded in vitro with disease-related prions obtained from different species, was subjected to serial rounds of PMCA. De novo rabbit prions produced in vitro from unseeded material were tested for infectivity in rabbits, with one of three intracerebrally challenged animals succumbing to disease at 766 d and displaying all of the characteristics of a TSE, thereby demonstrating that leporids are not resistant to prion infection. Material from the brain of the clinically affected rabbit containing abnormal prion protein resulted in a 100% attack rate after its inoculation in transgenic mice overexpressing rabbit PrP. Transmissibility to rabbits (>470 d) has been confirmed in 2 of 10 rabbits after intracerebral challenge. Despite rabbits no longer being able to be classified as resistant to TSEs, an outbreak of "mad rabbit disease" is unlikely.
C1 [Fernandez-Borges, Natalia; Castilla, Joaquin] CIC BioGUNE, Derio 48160, Bizkaia, Spain.
   [Chianini, Francesca; Gibbard, Louise; Hamilton, Scott; Eaton, Samantha L.; Finlayson, Jeanie; Pang, Yvonne; Steele, Philip; Reid, Hugh W.; Dagleish, Mark P.] Moredun Res Inst, Edinburgh EH26 0PZ, Midlothian, Scotland.
   [Castilla, Joaquin] Basque Fdn Sci, IKERBASQUE, Bilbao 48011, Bizkaia, Spain.
   [Priola, Suzette A.] NIAID, Lab Persistent Viral Dis, NIH, Hamilton, MT 59840 USA.
   [Fernandez-Borges, Natalia; de Castro, Jorge; Castilla, Joaquin] Scripps Florida, Dept Infectol, Jupiter, FL 33458 USA.
   [Vidal, Enric] Univ Autonoma Barcelona, UAB IRTA, CReSA, E-08193 Barcelona, Spain.
   [Pintadoe, Belen] CNB, Madrid 28049, Spain.
RP Castilla, J (reprint author), CIC BioGUNE, Derio 48160, Bizkaia, Spain.
EM castilla@joaquincastilla.com
RI Castilla, Joaquin/E-6952-2012; Fernandez-Borges, Natalia/H-1875-2012;
   Castilla, Joaquin/D-5261-2011; Chianini, Francesca/K-1451-2013; Pintado,
   Belen/N-3233-2014; 
OI Castilla, Joaquin/0000-0002-2216-1361; Chianini,
   Francesca/0000-0001-9962-446X; Pintado, Belen/0000-0002-8485-2520;
   Vidal, Enric/0000-0002-4965-3286
FU national grants from Spain [AGL2009-11553-C02-01, AGL2008-05296-C02];
   Basque government [PI2010-18]; National Institutes of Health (NIH)
   [1R01NS060790-01A2]; NIH, National Institute of Allergy and Infectious
   Diseases [1-Z01-AI000752-12]; Scripps and the Moredun Research Institute
FX The authors acknowledge the IKERBASQUE Foundation; support for vivarium
   and maintenance from CIC bioGUNE; Drs. Jean E. Jewel and Tomas Mayoral
   for the CWD and BSE brain tissue samples; Drs. Silvia Siso (AHVLA
   Lasswade), Ashwin Woodhoo (CIC bioGUNE), and Mike Fontaine (MRI) for
   useful discussion and advice; the Roslin Institute for use of equipment;
   and Moredun Bioservices for care and maintenance of animals. This work
   was financially supported by national grants from Spain
   (AGL2009-11553-C02-01 and AGL2008-05296-C02); Basque government Grant
   PI2010-18; National Institutes of Health (NIH) Grant 1R01NS060790-01A2;
   Intramural Research Program of the NIH, National Institute of Allergy
   and Infectious Diseases 1-Z01-AI000752-12; and Etortek Research Programs
   2011/2013, Scripps and the Moredun Research Institute.
NR 24
TC 28
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U1 4
U2 18
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 MAR 27
PY 2012
VL 109
IS 13
BP 5080
EP 5085
DI 10.1073/pnas.1120076109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 917HT
UT WOS:000302164200074
PM 22416127
ER

PT J
AU Gladwin, MT
   Sachdev, V
AF Gladwin, Mark T.
   Sachdev, Vandana
TI Cardiovascular Abnormalities in Sickle Cell Disease
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Review
DE cell; disease; sickle
ID PULMONARY ARTERIAL-HYPERTENSION; VENTRICULAR DIASTOLIC DYSFUNCTION;
   SYSTOLIC HEART-FAILURE; MYOCARDIAL-ISCHEMIA; EXERCISE CAPACITY; FREE
   HEMOGLOBIN; CARDIAC ABNORMALITIES; OXYGEN DESATURATION; TISSUE DOPPLER;
   ADULT PATIENTS
AB Sickle cell disease is characterized by recurrent episodes of ischemia-reperfusion injury to multiple vital organ systems and a chronic hemolytic anemia, both contributing to progressive organ dysfunction. The introduction of treatments that induce protective fetal hemoglobin and reduce infectious complications has greatly prolonged survival. However, with increased longevity, cardiovascular complications are increasingly evident, with the notable development of a progressive proliferative systemic vasculopathy, pulmonary hypertension (PH), and left ventricular diastolic dysfunction. Pulmonary hypertension is reported in autopsy studies, and numerous clinical studies have shown that increased pulmonary pressures are an important risk marker for mortality in these patients. In epidemiological studies, the development of PH is associated with intravascular hemolysis, cutaneous leg ulceration, renal insufficiency, iron overload, and liver dysfunction. Chronic anemia in sickle cell disease results in cardiac chamber dilation and a compensatory increase in left ventricular mass. This is often accompanied by left ventricular diastolic dysfunction that has also been a strong independent predictor of mortality in patients with sickle cell disease. Both PH and diastolic dysfunction are associated with marked abnormalities in exercise capacity in these patients. Sudden death is an increasingly recognized problem, and further cardiac investigations are necessary to recognize and treat high-risk patients. (J Am Coll Cardiol 2012; 59: 1123-33) (C) 2012 by the American College of Cardiology Foundation
C1 [Gladwin, Mark T.] Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15213 USA.
   [Gladwin, Mark T.] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA 15213 USA.
   [Sachdev, Vandana] NHLBI, Cardiovasc & Pulm, NIH, Bethesda, MD 20892 USA.
RP Gladwin, MT (reprint author), Univ Pittsburgh, Montefiore Hosp, 3459 5th Ave,NW 628, Pittsburgh, PA 15213 USA.
EM gladwinmt@upmc.edu
FU National Heart, Lung, and Blood Institute, National Institutes of
   Health, Department of Health and Human Services; NIH [R01HL098032,
   RO1HL096973, PO1HL103455]; Institute for Transfusion Medicine;
   Hemophilia Center of Western Pennsylvania
FX This work was supported in part by the Intramural Research Program of
   the National Heart, Lung, and Blood Institute, National Institutes of
   Health, Department of Health and Human Services. Dr. Gladwin receives
   research support from NIH grants R01HL098032, RO1HL096973, and
   PO1HL103455, the Institute for Transfusion Medicine and the Hemophilia
   Center of Western Pennsylvania. Dr. Sachdev has reported that she has no
   relationships relevant to the contents of this paper to disclose.
NR 104
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U1 3
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 27
PY 2012
VL 59
IS 13
BP 1123
EP 1133
DI 10.1016/j.jacc.2011.10.900
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 914LB
UT WOS:000301950300002
PM 22440212
ER

PT J
AU McDermott, MM
   Liu, KA
   Tian, L
   Guralnik, JM
   Criqui, MH
   Liao, YH
   Ferrucci, L
AF McDermott, Mary M.
   Liu, Kiang
   Tian, Lu
   Guralnik, Jack M.
   Criqui, Michael H.
   Liao, Yihua
   Ferrucci, Luigi
TI Calf Muscle Characteristics, Strength Measures, and Mortality in
   Peripheral Arterial Disease A Longitudinal Study
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE intermittent claudication; mortality; physical functioning; prognosis
ID LOWER-EXTREMITY ISCHEMIA; ANKLE BRACHIAL INDEX; SKELETAL-MUSCLE;
   FUNCTIONAL PERFORMANCE; PHYSICAL-ACTIVITY; CLAUDICATION; ASSOCIATIONS;
   IMPAIRMENT; PREVALENCE; SYMPTOMS
AB Objectives This study analyzed whether lower calf muscle density and poorer upper and lower extremity strength are associated with higher mortality rates in men and women with peripheral arterial disease (PAD).
   Background Men and women with lower extremity PAD have lower calf muscle density and reduced lower extremity strength compared with individuals without PAD.
   Methods At baseline, participants underwent measurement of calf muscle density with computed tomography in addition to knee extension power and isometric knee extension, plantar flexion, and hand grip strength measures. Participants were followed up annually for up to 4 years.
   Results were adjusted for age, sex, race, body mass index, ankle-brachial index, smoking, physical activity, and comorbidities. Results Among 434 PAD participants, 103 (24%) died during a mean follow-up of 47.6 months. Lower calf muscle density was associated with higher all-cause mortality (lowest density tertile hazard ratio [HR]: 1.80 [95% confidence interval (CI): 1.07 to 3.03], second tertile HR: 0.91 (95% CI: 0.51 to 1.62); highest density tertile HR: 1.00; p trend = 0.020) and higher cardiovascular disease mortality (lowest density tertile HR: 2.39 [95% CI: 0.90 to 6.30], second tertile HR: 0.85 [95% CI: 0.27 to 2.71]; highest density tertile HR: 1.00; p trend = 0.047). Poorer plantar flexion strength (p trend = 0.004), lower baseline leg power (p trend = 0.046), and poorer handgrip (p trend = 0.005) were associated with higher all-cause mortality.
   Conclusions These data demonstrate that lower calf muscle density and weaker plantar flexion strength, knee extension power, and hand grip were associated with increased mortality in these participants with PAD, independently of the ankle-brachial index and other confounders. (J Am Coll Cardiol 2012; 59: 1159-67) (C) 2012 by the American College of Cardiology Foundation
C1 [McDermott, Mary M.] Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA.
   [McDermott, Mary M.; Liu, Kiang; Liao, Yihua] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
   [Tian, Lu] Stanford Univ, Dept Hlth Res & Policy Biostat, Palo Alto, CA 94304 USA.
   [Guralnik, Jack M.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
   [Criqui, Michael H.] Univ Calif San Diego, Div Prevent Med, San Diego, CA 92103 USA.
   [Ferrucci, Luigi] NIA, Intramural Res Program, Bethesda, MD 20892 USA.
RP McDermott, MM (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Med, 750 N Lake Shore Dr,10th Floor, Chicago, IL 60611 USA.
EM mdm608@northwestern.edu
FU National Heart, Lung, and Blood Institute [R01-HL58099, R01-HL64739,
   R01-HL071223, R01-HL076298, R01-HL083064]; National Center for Research
   Resources, National Institutes of Health [RR-00048]; National Institute
   on Aging, National Institutes of Health
FX This study was supported by grants R01-HL58099, R01-HL64739,
   R01-HL071223, R01-HL076298, and R01-HL083064 from the National Heart,
   Lung, and Blood Institute and by grant RR-00048 from the National Center
   for Research Resources, National Institutes of Health. Supported in part
   by the Intramural Research Program, National Institute on Aging,
   National Institutes of Health. The authors have reported that they have
   no relationships relevant to the contents of this paper to disclose.
   Alan T. Hirsch, MD, served as Guest Editor for this paper.
NR 24
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U1 2
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 27
PY 2012
VL 59
IS 13
BP 1159
EP 1167
DI 10.1016/j.jacc.2011.12.019
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 914LB
UT WOS:000301950300006
PM 22440216
ER

PT J
AU Belanger, JM
   Raviv, Y
   Viard, M
   Baxa, U
   Blumenthal, R
AF Belanger, Julie M.
   Raviv, Yossef
   Viard, Mathias
   Baxa, Ulrich
   Blumenthal, Robert
TI Orthogonal inactivation of influenza and the creation of detergent
   resistant viral aggregates: towards a novel vaccine strategy
SO VIROLOGY JOURNAL
LA English
DT Article
DE Influenza virus; Detergent; Detergent resistance; Hemagglutinin; Triton;
   Vaccine; Inactivation; Human immunodeficiency virus; HIV-1; Orthogonal
ID STRUCTURAL INTEGRITY; VIRUS INACTIVATION; UVA IRRADIATION; PRESERVATION;
   PROTEINS; NUCLEOPROTEIN; MEMBRANES
AB Background: It has been previously shown that enveloped viruses can be inactivated using aryl azides, such as 1-iodo- 5-azidonaphthalene (INA), plus UVA irradiation with preservation of surface epitopes in the inactivated virus preparations. Prolonged UVA irradiation in the presence of INA results in ROS-species formation, which in turn results in detergent resistant viral protein fractions.
   Results: Herein, we characterize the applicability of this technique to inactivate influenza. It is shown that influenza virus + INA (100 micromolar) + UVA irradiation for 30 minutes results in a significant (p < 0.05) increase in pelletablehemagglutinin after Triton X-100 treatment followed by ultracentrifugation. Additionally, characterization of the virus suspension by immunogold labeling in cryo-EM, and viral pellet characterization via immunoprecipitation with a neutralizing antibody, shows preservation of neutralization epitopes after this treatment.
   Conclusion: These orthogonally inactivated viral preparations with detergent resistant fractions are being explored as a novel route for safe, effective inactivated vaccines generated from a variety of enveloped viruses.
C1 [Belanger, Julie M.; Blumenthal, Robert] NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21701 USA.
   [Raviv, Yossef; Viard, Mathias] NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21702 USA.
   [Baxa, Ulrich] NCI, Adv Technol Program, SAIC Frederick, Frederick, MD 21702 USA.
   [Belanger, Julie M.] Kings Coll, Dept Chem & Phys, Wilkes Barre, PA USA.
RP Blumenthal, R (reprint author), NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21701 USA.
EM blumenthalr@mail.nih.govc
RI Belanger, Julie/A-5734-2009
OI Belanger, Julie/0000-0002-7236-2778
FU National Cancer Institute, National Institutes of Health
   [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer
   Research; NIAID
FX This project has been funded in whole or in part with federal funds from
   the National Cancer Institute, National Institutes of Health, under
   contract HHSN261200800001E. This research was supported [in part] by the
   Intramural Research Program of the NIH, National Cancer Institute,
   Center for Cancer Research. Further funding was provided by a grant from
   the NIAID Intramural Biodefense Research Program. 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 20
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U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1743-422X
J9 VIROL J
JI Virol. J.
PD MAR 26
PY 2012
VL 9
AR 72
DI 10.1186/1743-422X-9-72
PG 12
WC Virology
SC Virology
GA 950OH
UT WOS:000304658100001
PM 22449007
ER

PT J
AU Bahta, M
   Lountos, GT
   Beverly, D
   Ulrich, RG
   Waugh, DS
   Burke, TR
AF Bahta, Medhanit
   Lountos, George T.
   Beverly, Dyas
   Ulrich, Robert G.
   Waugh, David S.
   Burke, Terrence R., Jr.
TI Nitrophenylphosphate substrate screening and oxime-based ligation for
   the development of nanomolar affinity inhibitors of the Yersinia pestis
   protein tyrosine phosphatase YopH
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 243rd National Spring Meeting of the American-Chemical-Society
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc
C1 [Bahta, Medhanit; Burke, Terrence R., Jr.] NCI, Biol Chem Lab, Frederick, MD 21702 USA.
   [Lountos, George T.; Waugh, David S.] NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA.
   [Beverly, Dyas; Ulrich, Robert G.] USAMRIID, Lab Mol Immunol, Frederick, MD 21702 USA.
EM bahtam@mail.nih.gov
RI Lountos, George/B-3983-2015
NR 0
TC 0
Z9 0
U1 0
U2 1
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 MAR 25
PY 2012
VL 243
MA 34-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219JX
UT WOS:000324503201692
ER

PT J
AU Barchi, JJ
AF Barchi, Joseph J.
TI Various nano-guises of the TF antigen for anticancer therapy
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
   Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Barchi, Joseph J.] NCI, Frederick, MD 21701 USA.
EM barchi@helix.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 13-CARB
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475101083
ER

PT J
AU Basant, N
   Roth, B
   Habib, M
   Wang, XS
AF Basant, Nikita
   Roth, Bryan
   Habib, Muhammad
   Wang, Xiang Simon
TI Shape-based screening by hybrid query assisted with molecular docking to
   mine diverse and selective histone deacetylase (HD2) inhibitors
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
   Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Basant, Nikita; Habib, Muhammad; Wang, Xiang Simon] Howard Univ, Coll Pharm, Dept Pharmaceut Sci, Washington, DC 20059 USA.
   [Roth, Bryan] Univ N Carolina, NIMH, Psychoact Drug Screening Program, Chapel Hill, NC 27599 USA.
   [Roth, Bryan] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA.
EM nikita_basant@yahoo.com
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 571-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475104730
ER

PT J
AU Battistel, MD
   Shangold, M
   Trinh, L
   Shiloach, J
   Freedberg, DI
AF Battistel, Marcos D.
   Shangold, Michael
   Trinh, Loc
   Shiloach, Joseph
   Freedberg, Daron I.
TI Hydrogen bonding, the foundations of helicity in a tetramer of alpha 2-8
   sialic acid
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
   Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Battistel, Marcos D.; Shangold, Michael; Freedberg, Daron I.] US FDA, CBER, OVRR, Rockville, MD 20852 USA.
   [Trinh, Loc] NIH, SBDPI, Bethesda, MD 20892 USA.
   [Shiloach, Joseph] NIDDK, NIH, Bethesda, MD 20892 USA.
EM battiste@helix.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 131-CARB
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475101194
ER

PT J
AU Bolton, E
AF Bolton, Evan
TI New strategies to normalize chemical structure representations and
   weed-out impractical small molecules
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
   Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Bolton, Evan] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
EM bolton@ncbi.nlm.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 54-CINF
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475103388
ER

PT J
AU Cheruku, P
   Plaza, A
   Keffer, JL
   Bewley, CA
AF Cheruku, Pradeep
   Plaza, Alberto
   Keffer, Jessica L.
   Bewley, Carole A.
TI Namalide, a natural cyclic peptide and its analogs as carboxypeptidase A
   inhibitors
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 243rd National Spring Meeting of the American-Chemical-Society
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc
C1 [Cheruku, Pradeep; Plaza, Alberto; Keffer, Jessica L.; Bewley, Carole A.] NIDDK, Dept Bioorgan Chem, NIH, Bethesda, MD 20878 USA.
EM cherukup@niddk.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 MAR 25
PY 2012
VL 243
MA 110-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219JX
UT WOS:000324503201766
ER

PT J
AU Chung, HS
   Gopich, IV
   McHale, K
   Louis, JM
   Eaton, WA
AF Chung, Hoi Sung
   Gopich, Irina V.
   McHale, Kevin
   Louis, John M.
   Eaton, William A.
TI Measurement of average transition-path time for protein folding in
   single molecule FRET experiments
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 243rd National Spring Meeting of the American-Chemical-Society
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc
C1 [Chung, Hoi Sung; Gopich, Irina V.; McHale, Kevin; Louis, John M.; Eaton, William A.] NIDDK, LCP, NIH, Bethesda, MD 20892 USA.
EM chunghoi@niddk.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 MAR 25
PY 2012
VL 243
MA 56-PHYS
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219JX
UT WOS:000324503203306
ER

PT J
AU Dogo-Isonagie, C
   Lam, S
   Acharya, P
   Kwong, P
   Bewley, C
AF Dogo-Isonagie, Cajetan
   Lam, Son
   Acharya, Priyamvada
   Kwong, Peter
   Bewley, Carole
TI Synthetic CCR5-derived peptides that inhibit HIV entry
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 243rd National Spring Meeting of the American-Chemical-Society
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc
C1 [Dogo-Isonagie, Cajetan; Lam, Son; Bewley, Carole] NIH, Bioorgan Chem Lab, Bethesda, MD 20892 USA.
   [Acharya, Priyamvada; Kwong, Peter] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
EM dogoisonagieci@niddk.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 405-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219JX
UT WOS:000324503202064
ER

PT J
AU Dogo-Isonagie, C
   Lam, SN
   Archaya, P
   Kwong, PD
   Bewley, CA
AF Dogo-Isonagie, Cajetan
   Lam, Son N.
   Archaya, Priyamvada
   Kwong, Peter D.
   Bewley, Carole A.
TI Insights into interactions of the GCPR CCR5 with the HIV viral envelope
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 243rd National Spring Meeting of the American-Chemical-Society
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc
C1 [Dogo-Isonagie, Cajetan; Lam, Son N.; Bewley, Carole A.] NIDDK, NIH, Bioorgan Chem Lab, Bethesda, MD 20892 USA.
   [Archaya, Priyamvada; Kwong, Peter D.] NIAID, NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
EM dogoisonagieci@niddk.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
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 MAR 25
PY 2012
VL 243
MA 273-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219JX
UT WOS:000324503201923
ER

PT J
AU Dutta, AK
   Peterson, AW
   Zhao, HY
   He, HJ
   Zangmeister, R
   Schuck, P
   Tarlov, MJ
AF Dutta, Amit K.
   Peterson, Alexander W.
   Zhao, Huaying
   He, Hua-Jun
   Zangmeister, Rebecca
   Schuck, Peter
   Tarlov, Michael J.
TI Effect of lectin-glycoprotein binding strength on glycoanalysis
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
   Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Dutta, Amit K.; Peterson, Alexander W.; He, Hua-Jun; Zangmeister, Rebecca; Tarlov, Michael J.] NIST, Div Biochem Sci, Mat Measurements Lab, Gaithersburg, MD 20899 USA.
   [Dutta, Amit K.; Zhao, Huaying; Schuck, Peter] NIBIB, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD USA.
EM duttabapi2@gmail.com
RI Zangmeister, Rebecca/D-6641-2017
OI Zangmeister, Rebecca/0000-0002-0540-6240
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 76-BIOT
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475100615
ER

PT J
AU Gawrisch, K
   Gaede, HC
   Soubias, O
   Teague, WE
   Casas, R
   Dustman, JM
AF Gawrisch, Klaus
   Gaede, Holly C.
   Soubias, Olivier
   Teague, Walter E., Jr.
   Casas, Rachel
   Dustman, John M.
TI Influence of phospholipid chemical structure on lateral diffusion rates
   in fluid bilayers
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
   Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Gawrisch, Klaus; Soubias, Olivier; Teague, Walter E., Jr.; Casas, Rachel; Dustman, John M.] NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA.
   [Gaede, Holly C.] Texas A&M Univ, Dept Chem, College Stn, TX 77843 USA.
EM gawrisch@helix.nih.gov
RI Gaede, Holly/B-7392-2015
OI Gaede, Holly/0000-0003-4444-4394
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 88-COLL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475103545
ER

PT J
AU Gildersleeve, J
AF Gildersleeve, Jeffrey
TI Personalizing cancer treatment with the aid of glycan array technology
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
   Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Gildersleeve, Jeffrey] NCI, Biol Chem Lab, Frederick, MD 21702 USA.
EM gildersj@mail.nih.gov
NR 0
TC 0
Z9 0
U1 1
U2 1
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 MAR 25
PY 2012
VL 243
MA 15-CARB
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475101085
ER

PT J
AU Hager, G
AF Hager, Gordon
TI How transcription factors bind to chromatin
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 243rd National Spring Meeting of the American-Chemical-Society
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc
C1 [Hager, Gordon] NCI, Ctr Excellence Chromosome Biol, NIH, Bethesda, MD 20892 USA.
EM hagerg@exchange.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 12-LIFE
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219JX
UT WOS:000324503201648
ER

PT J
AU Hakkinen, P
AF Hakkinen, Pertti
TI (US) National Library of Medicine's downloadable, online, and smartphone
   tools for first responders and others, Part 2: CHEMM (Chemical Hazards
   Emergency Medical Management)
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
   Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Hakkinen, Pertti] NIH, Specialized Informat Serv, Natl Lib Med, Bethesda, MD 20892 USA.
EM hakkinenp@mail.nlm.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 21-CHAS
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475101702
ER

PT J
AU Horkay, F
   Basser, PJ
   Hecht, AM
   Geissler, E
AF Horkay, Ferenc
   Basser, Peter J.
   Hecht, Anne-Marie
   Geissler, Erik
TI Proteoglycan assemblies in cartilage
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 243rd National Spring Meeting of the American-Chemical-Society
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc
C1 [Horkay, Ferenc; Basser, Peter J.] NICHD, NIH, Bethesda, MD 20892 USA.
   [Hecht, Anne-Marie; Geissler, Erik] Univ Grenoble 1, Spectrometrie Phys Lab, F-38402 St Martin Dheres, France.
EM horkay@helix.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
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 MAR 25
PY 2012
VL 243
MA 441-PMSE
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219JX
UT WOS:000324503204158
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 Nanomechanical properties of cartilage
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
   Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Horkay, Ferenc; Horkayne-Szakaly, Iren; Silva, Candida; Basser, Peter J.] NICHD, NIH, Bethesda, MD 20892 USA.
   [Dimitriadis, Emilios K.] NIBIB, NIH, Bethesda, MD 20892 USA.
EM horkay@helix.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
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 MAR 25
PY 2012
VL 243
MA 457-BIOT
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475100979
ER

PT J
AU Hou, SJ
   Sail, D
   Kovac, P
AF Hou, Shu-jie
   Sail, Deepak
   Kovac, Pavol
TI First chemical synthesis of the conjugation ready hexasaccharide antigen
   of Vibrio cholerae O:139
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
   Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Hou, Shu-jie; Sail, Deepak; Kovac, Pavol] NIDDK, LBC, Sect Carbohydrates, NIH, Bethesda, MD 20892 USA.
EM saild@mail.nih.gov
RI Kovac, Pavol/B-8813-2008
OI Kovac, Pavol/0000-0001-5044-3449
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 89-CARB
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475101154
ER

PT J
AU Jacobson, KA
   Stevens, RC
   Abagyan, R
   Deflorian, F
   Gao, ZG
   Gakh, AA
   Tosh, DK
   Kumar, TS
   Xu, F
   Katritch, V
AF Jacobson, Kenneth A.
   Stevens, Raymond C.
   Abagyan, Ruben
   Deflorian, Francesca
   Gao, Zhan-Guo
   Gakh, Andrei A.
   Tosh, Dilip K.
   Kumar, T. S.
   Xu, Fei
   Katritch, Vsevolod
TI Structure-based design of adenosine receptor ligands
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 243rd National Spring Meeting of the American-Chemical-Society
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc
C1 [Jacobson, Kenneth A.; Deflorian, Francesca; Gao, Zhan-Guo; Gakh, Andrei A.; Tosh, Dilip K.; Kumar, T. S.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
   [Abagyan, Ruben] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA 92063 USA.
   [Stevens, Raymond C.; Xu, Fei; Katritch, Vsevolod] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA.
   [Stevens, Raymond C.; Xu, Fei; Katritch, Vsevolod] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA.
EM kajacobs@helix.nih.gov
RI Jacobson, Kenneth/A-1530-2009; Katritch, Vsevolod/Q-8357-2016
OI Jacobson, Kenneth/0000-0001-8104-1493; 
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 275-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219JX
UT WOS:000324503201925
ER

PT J
AU Jiang, ZP
   McGlinchey, RP
   Pfefferkorn, CM
   Yap, TL
   Lee, JC
AF Jiang, Zhiping
   McGlinchey, Ryan P.
   Pfefferkorn, Candace M.
   Yap, Thai Leong
   Lee, Jennifer C.
TI From unstructured to a-helical to b-sheet: Fluorescent studies of
   apolipoprotein c-III, a-synuclein, and the Pmel17 repeat domain
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 243rd National Spring Meeting of the American-Chemical-Society
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc
C1 [Jiang, Zhiping; McGlinchey, Ryan P.; Pfefferkorn, Candace M.; Yap, Thai Leong; Lee, Jennifer C.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
EM leej4@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 87-PHYS
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219JX
UT WOS:000324503203337
ER

PT J
AU Keck, GE
   Poudel, YB
   Cummins, TJ
   Rudra, A
   Covel, JA
   Kedei, N
   Lewin, NE
   Blumberg, PM
AF Keck, Gary E.
   Poudel, Yam B.
   Cummins, Thomas J.
   Rudra, Arnab
   Covel, Jonathan A.
   Kedei, Noemi
   Lewin, Nancy E.
   Blumberg, Peter M.
TI Total synthesis and biological evaluation of bryostatin 7
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 243rd National Spring Meeting of the American-Chemical-Society
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc
C1 [Keck, Gary E.; Poudel, Yam B.; Rudra, Arnab; Covel, Jonathan A.; Kedei, Noemi] Univ Utah, Dept Chem, Salt Lake City, UT 84112 USA.
   [Kedei, Noemi; Lewin, Nancy E.; Blumberg, Peter M.] NCI, NIH, LCBG, Ctr Canc Res, Bethesda, MD 20892 USA.
EM ypoudel@scripps.edu
NR 0
TC 0
Z9 0
U1 0
U2 1
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 MAR 25
PY 2012
VL 243
MA 232-ORGN
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219JX
UT WOS:000324503202449
ER

PT J
AU Kiselev, E
   Agama, K
   Pommier, Y
   Cushman, M
AF Kiselev, Evgeny
   Agama, Keli
   Pommier, Yves
   Cushman, Mark
TI Structure-activity relationship study of azaindenoisoquinoline
   topoisomerase I inhibitors
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 243rd National Spring Meeting of the American-Chemical-Society
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc
C1 [Kiselev, Evgeny; Cushman, Mark] Purdue Univ, Dept Med Chem & Mol Pharmacol, Sch Pharm, W Lafayette, IN 47906 USA.
   [Kiselev, Evgeny; Cushman, Mark] Purdue Univ, Purdue Ctr Canc Res, W Lafayette, IN 47906 USA.
   [Agama, Keli; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
EM ekiselev@purdue.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 450-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219JX
UT WOS:000324503202106
ER

PT J
AU Klitzing, HA
   Lou, KY
   Zimmerberg, J
   Weber, PK
   Kraft, ML
AF Klitzing, Haley A.
   Lou, Kaiyan
   Zimmerberg, Joshua
   Weber, Peter K.
   Kraft, Mary L.
TI High-resolution secondary ion mass spectrometry reveals changes in long
   range sphingolipid organization with time
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
   Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Klitzing, Haley A.; Kraft, Mary L.] Univ Illinois, Dept Chem, Urbana, IL 61801 USA.
   [Lou, Kaiyan; Kraft, Mary L.] Univ Illinois, Dept Chem & Biomol Engn, Urbana, IL 61801 USA.
   [Zimmerberg, Joshua] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
   [Weber, Peter K.] Lawrence Livermore Natl Lab, Glenn T Seaborg Inst, Livermore, CA 94551 USA.
EM klitzin1@illinois.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 234-BIOL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475100521
ER

PT J
AU Kobayashi, H
   Mitsunaga, M
   Ogawa, M
   Choyke, PL
AF Kobayashi, Hisataka
   Mitsunaga, Makoto
   Ogawa, Mikako
   Choyke, Peter L.
TI Photo-immunotherapy: A super-controlled molecular target-specific cancer
   theranostics, evolving from the molecular imaging technology
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
   Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Kobayashi, Hisataka; Mitsunaga, Makoto; Ogawa, Mikako; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
EM kobayash@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
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 MAR 25
PY 2012
VL 243
MA 36-BIOT
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475100576
ER

PT J
AU Kosa, N
   Foley, T
   Burkart, M
AF Kosa, Nicolas
   Foley, Timothy
   Burkart, Michael
TI Fluorescent-based inhibitor screening for Sfp-type PPTases
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
   Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Kosa, Nicolas; Foley, Timothy; Burkart, Michael] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA.
   [Foley, Timothy] NIH, Chem Genom Ctr, Rockville, MD 20850 USA.
EM nkosa@ucsd.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 70-BIOL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475100403
ER

PT J
AU Kraft, ML
   Frisz, JF
   Klitzing, HA
   Lou, KY
   Hanafin, WP
   Wilson, RL
   Lizunov, V
   Carpenter, KJ
   Zimmerberg, J
   Weber, PK
AF Kraft, Mary L.
   Frisz, Jessica F.
   Klitzing, Haley A.
   Lou, Kaiyan
   Hanafin, William P.
   Wilson, Robert L.
   Lizunov, Vladimir
   Carpenter, Kevin J.
   Zimmerberg, Joshua
   Weber, Peter K.
TI High-resolution secondary ion mass spectrometry reveals the cholesterol
   and lipid distribution within the plasma membranes of fibroblast cells
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
   Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Kraft, Mary L.; Lou, Kaiyan; Hanafin, William P.] Univ Illinois, Dept Chem & Biomol Engn, Urbana, IL 61801 USA.
   [Kraft, Mary L.; Frisz, Jessica F.; Klitzing, Haley A.; Wilson, Robert L.] Univ Illinois, Dept Chem, Urbana, IL 61801 USA.
   [Carpenter, Kevin J.; Weber, Peter K.] Lawrence Livermore Natl Lab, Glenn T Seaborg Inst, Livermore, CA 94551 USA.
   [Lizunov, Vladimir; Zimmerberg, Joshua] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
EM mlkraft@illinois.edu
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 MAR 25
PY 2012
VL 243
MA 198-COLL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475103651
ER

PT J
AU Lee, J
   Dona, V
   Boshoff, HI
   Barry, CE
AF Lee, Jinwoo
   Dona, Valentina
   Boshoff, Helena I.
   Barry, Clifton E.
TI Synthesis and structure activity relationship of pyrazole derivatives as
   anti-tuberculosis agents
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 243rd National Spring Meeting of the American-Chemical-Society
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc
C1 [Lee, Jinwoo; Dona, Valentina; Boshoff, Helena I.; Barry, Clifton E.] NIAID, TB Res Sect, NIH, Bethesda, MD 20892 USA.
EM jinwoo.lee@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 150-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219JX
UT WOS:000324503201805
ER

PT J
AU Li, FY
AF Li, Fuying
TI Probes for narcotic receptor mediated phenomena: Conceputalization,
   synthesis and pharmacological evaluation of ring-expanded Phenylmorphans
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 243rd National Spring Meeting of the American-Chemical-Society
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc
C1 [Li, Fuying] NIDA, Drug Design & Synth Sect, Chem Biol Res Branch, Rockville, MD 20852 USA.
EM lif4@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 129-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219JX
UT WOS:000324503201784
ER

PT J
AU Loesgen, S
   Shahzad-Ul-Hussan, S
   Bewley, CA
AF Loesgen, Sandra
   Shahzad-Ul-Hussan, Syed
   Bewley, Carole A.
TI HIV-1 Inhibitors from nature: Understanding and optimizing potent
   cyanobacterial carbohydrate-binding proteins
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
   Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Loesgen, Sandra; Bewley, Carole A.] NIH, Bioorgan Chem Lab, Bethesda, MD 20892 USA.
   [Shahzad-Ul-Hussan, Syed] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
EM sandra.loesgen@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 28-CARB
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475101095
ER

PT J
AU Lusvarghi, S
   O'Keefe, BR
   Le Grice, SFJ
AF Lusvarghi, Sabrina
   O'Keefe, Barry R.
   Le Grice, Stuart F. J.
TI Metallomicrobicides: A smarter way to target HIV
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
   Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Lusvarghi, Sabrina; O'Keefe, Barry R.; Le Grice, Stuart F. J.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.
EM sabrinal@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 279-BIOL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475100526
ER

PT J
AU Michino, M
   Duan, LH
   Han, Y
   Donthamsetti, P
   Banala, A
   Newman, AH
   Javitch, JA
   Shi, L
AF Michino, Mayako
   Duan, Lihua
   Han, Yang
   Donthamsetti, Prashant
   Banala, Ashwini
   Newman, Amy H.
   Javitch, Jonathan A.
   Shi, Lei
TI Structural basis for dopamine D3 receptor subtype-selectivity
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
   Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Michino, Mayako; Shi, Lei] Cornell Univ, Weill Cornell Med Coll, Dept Physiol & Biophys, New York, NY 10021 USA.
   [Michino, Mayako; Shi, Lei] Cornell Univ, Weill Cornell Med Coll, HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsau, New York, NY 10021 USA.
   [Duan, Lihua; Han, Yang; Donthamsetti, Prashant; Javitch, Jonathan A.] Columbia Univ Coll Phys & Surg, Ctr Mol Recognit, New York, NY 10032 USA.
   [Duan, Lihua; Han, Yang; Donthamsetti, Prashant; Javitch, Jonathan A.] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA.
   [Duan, Lihua; Han, Yang; Donthamsetti, Prashant; Javitch, Jonathan A.] Columbia Univ Coll Phys & Surg, Dept Pharmacol, New York, NY 10032 USA.
   [Banala, Ashwini; Newman, Amy H.] NIDA, Med Chem Sect, Intramural Res Program, Baltimore, MD 21224 USA.
EM mam2134@med.cornell.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 359-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475104540
ER

PT J
AU Moore, NM
AF Moore, Nicole M.
TI Convergence of physical and life sciences perspectives in cancer
   research
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 243rd National Spring Meeting of the American-Chemical-Society
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc
C1 [Moore, Nicole M.] NCI, Off Phys Sci Oncol, Bethesda, MD 20892 USA.
EM moorenm@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
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 MAR 25
PY 2012
VL 243
MA 372-POLY
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219JX
UT WOS:000324503204617
ER

PT J
AU Munge, BS
   Coffey, AL
   Doucette, JM
   Somba, BK
   Malhotra, R
   Patel, V
   Gutkind, S
   Rusling, JF
AF Munge, Bernard S.
   Coffey, Amy L.
   Doucette, Jaimee M.
   Somba, Brian K.
   Malhotra, Ruchika
   Patel, Vyomesh
   Gutkind, Silvio
   Rusling, James F.
TI Nanostructured immunosensor for attomolar detection of cancer biomarkers
   using massively labeled superparamagnetic particles
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
   Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Munge, Bernard S.; Coffey, Amy L.; Doucette, Jaimee M.; Somba, Brian K.] Salve Regina Univ, Dept Chem, Newport, RI 02840 USA.
   [Malhotra, Ruchika; Rusling, James F.] Univ Connecticut, Dept Chem, Storrs, CT 06269 USA.
   [Patel, Vyomesh; Gutkind, Silvio] NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
EM bernard.munge@salve.edu
NR 0
TC 0
Z9 0
U1 0
U2 1
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 MAR 25
PY 2012
VL 243
MA 41-ANYL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475100174
ER

PT J
AU Namuswe, F
   Amann, BT
   Berg, JM
AF Namuswe, Frances
   Amann, Barbara T.
   Berg, Jeremy M.
TI Investigating the metal binding cooperativity between adjacent TRAF-like
   zinc finger domains
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
   Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Namuswe, Frances; Amann, Barbara T.] NIH, Mol Biol Lab, Bethesda, MD 20892 USA.
   [Berg, Jeremy M.] Univ Pittsburgh, Dept Computat & Syst Biol, Pittsburgh, PA 15213 USA.
EM namuswef@niddk.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 117-BIOL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475100445
ER

PT J
AU Nicklaus, MC
   Sitzmann, M
AF Nicklaus, Marc C.
   Sitzmann, Markus
TI Representing chemical information by URLs: The chemical identifier
   resolver as a general chemoinformatics tool
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
   Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Nicklaus, Marc C.; Sitzmann, Markus] NCI, NCI Frederick, NIH, Frederick, MD 21702 USA.
EM mn1@helix.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 109-CINF
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475103439
ER

PT J
AU North, H
   Scott, KR
   Stables, JP
   Wang, XS
AF North, Henry
   Scott, Kenneth R.
   Stables, James P.
   Wang, Xiang S.
TI Cheminfomatic modeling of enaminones anticonvulsants with dual set of
   animal activities
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
   Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [North, Henry; Scott, Kenneth R.; Wang, Xiang S.] Howard Univ, Coll Pharm, Dept Pharmaceut Sci CDRD, Washington, DC 20059 USA.
   [Stables, James P.] NINDS, Epilepsy Branch, Rockville, MD 20852 USA.
EM henry.north@howard.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 299-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475104483
ER

PT J
AU Okur, A
   Smith, DB
   Brooks, BR
AF Okur, Asim
   Smith, Daniel B.
   Brooks, Bernard R.
TI Evaluating the performance of reservoir replica exchange methods through
   transition state theory
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
   Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Okur, Asim; Brooks, Bernard R.] NHLBI, NIH, Bethesda, MD 20892 USA.
   [Smith, Daniel B.] Univ Pittsburgh, Dept Math, Pittsburgh, PA 15260 USA.
EM okura@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 214-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475104401
ER

PT J
AU Olsen, MJ
   Clewett, C
   Iacoban, P
   Hubbard, M
   Cox, T
   Stables, JP
AF Olsen, Mark J.
   Clewett, Cathy
   Iacoban, Paulina
   Hubbard, Matthew
   Cox, Thomas
   Stables, James P.
TI Synthesis and anticonvulsant activity of 4-aryl-2-hydroxytetronimides
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 243rd National Spring Meeting of the American-Chemical-Society
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc
C1 [Olsen, Mark J.; Iacoban, Paulina; Hubbard, Matthew; Cox, Thomas] Midwestern Univ, Dept Pharmaceut Sci, Glendale, AZ 85308 USA.
   [Clewett, Cathy] West Texas A&M Univ, Dept Math Chem & Phys, Canyon, TX 79015 USA.
   [Stables, James P.] NINDS, ASP Program, Rockville, MD 20852 USA.
EM molsen@midwestern.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 28-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219JX
UT WOS:000324503201686
ER

PT J
AU Qian, WJ
   Park, JE
   Liu, F
   Lim, D
   Scharow, A
   Berg, T
   Yaffe, MB
   Lee, KS
   Burke, TR
AF Qian, Wenjian
   Park, Jung-Eun
   Liu, Fa
   Lim, Dan
   Scharow, Andrej
   Berg, Thorsten
   Yaffe, Michael B.
   Lee, Kyung S.
   Burke, Terrence R., Jr.
TI Structure-based development of biovailable polo-like kinase 1 (Plk1)
   polo-box domain-binding peptides
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 243rd National Spring Meeting of the American-Chemical-Society
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc
C1 [Qian, Wenjian; Liu, Fa; Burke, Terrence R., Jr.] NCI, NIH, Biol Chem Lab, Frederick, MD 21702 USA.
   [Park, Jung-Eun; Lee, Kyung S.] NCI, NIH, Lab Metab, Bethesda, MD 20892 USA.
   [Lim, Dan; Yaffe, Michael B.] MIT, Dept Biol & Biol Engn, Ctr Canc Res, Cambridge, MA 02139 USA.
   [Scharow, Andrej; Berg, Thorsten] Univ Leipzig, Inst Organ Chem, D-04109 Leipzig, Germany.
EM qianw2@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 343-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219JX
UT WOS:000324503202004
ER

PT J
AU Rogers, SA
   Patnaik, S
   Marugan, J
   Sidransky, E
   Inglese, J
   Austin, CP
   Schoenen, F
   Aube, J
AF Rogers, Steven A.
   Patnaik, Samarjit
   Marugan, Juan
   Sidransky, Ellen
   Inglese, James
   Austin, Christopher P.
   Schoenen, Frank
   Aube, Jeffrey
TI Synthesis and biological evaluation of small molecule activators of the
   N370S mutant form of glucocerebrosidase as a potential therapy for
   Gaucher disease
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 243rd National Spring Meeting of the American-Chemical-Society
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc
C1 [Rogers, Steven A.; Schoenen, Frank; Aube, Jeffrey] Univ Kansas, Specialized Chem Ctr, Lawrence, KS 66044 USA.
   [Sidransky, Ellen] NIMH, Porter Neurosci Res Ctr, Mol Neurogenet Sect, Bethesda, MD 20892 USA.
   [Patnaik, Samarjit; Marugan, Juan; Inglese, James; Austin, Christopher P.] NIH, Ctr Translat Therapeut, Rockville, MD 20892 USA.
EM sarogers@ku.edu
NR 0
TC 0
Z9 0
U1 0
U2 1
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 MAR 25
PY 2012
VL 243
MA 455-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219JX
UT WOS:000324503202111
ER

PT J
AU Rosta, E
   Yang, W
   Hummer, G
AF Rosta, Edina
   Yang, Wei
   Hummer, Gerhard
TI On two-metal ion catalysis: Study in Ribonuclease H
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
   Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Rosta, Edina; Yang, Wei; Hummer, Gerhard] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM rosta@helix.nih.gov
RI Hummer, Gerhard/A-2546-2013
OI Hummer, Gerhard/0000-0001-7768-746X
NR 0
TC 0
Z9 0
U1 0
U2 1
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 MAR 25
PY 2012
VL 243
MA 537-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475104704
ER

PT J
AU Sitzmann, M
   Nicklaus, MC
AF Sitzmann, Markus
   Nicklaus, Marc C.
TI Accessing NCI/CADD web resources by InChI
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
   Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Sitzmann, Markus; Nicklaus, Marc C.] Natl Canc Inst Frederick, Biol Chem Lab, Ctr Canc Res, NIH,DHHS, Frederick, MD 21702 USA.
EM sitzmann@helix.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 112-CINF
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475103442
ER

PT J
AU Stephenson, RM
   Bhirde, A
   Chen, XY
   Walker, ARH
AF Stephenson, Rachel M.
   Bhirde, Ashwinkumar
   Chen, Xiaoyuan
   Walker, Angela R. Hight
TI Dispersant-dependence of the resonance Raman spectra and excitation
   profiles for aqueous SWCNT solutions
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
   Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Stephenson, Rachel M.; Walker, Angela R. Hight] NIST, Phys Measurement Lab, Gaithersburg, MD 20899 USA.
   [Bhirde, Ashwinkumar; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA.
EM rachel.stephenson@nist.gov
RI Hight Walker, Angela/C-3373-2009
OI Hight Walker, Angela/0000-0003-1385-0672
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 212-COLL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475103664
ER

PT J
AU Tosh, DK
   Phan, K
   Deflorian, F
   Wei, Q
   Gao, ZG
   Jacobson, KA
AF Tosh, Dilip K.
   Khai Phan
   Deflorian, Francesca
   Wei, Qiang
   Gao, Zhan-Guo
   Jacobson, Kenneth A.
TI Discovery of truncated (N)-methanocarba nucleosides as A(1) adenosine
   receptor agonists
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 243rd National Spring Meeting of the American-Chemical-Society
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc
C1 [Tosh, Dilip K.; Khai Phan; Deflorian, Francesca; Wei, Qiang; Gao, Zhan-Guo; Jacobson, Kenneth A.] NIDDK, NIH, Bioorgan Chem Lab, Bethesda, MD 20892 USA.
EM toshd@niddk.nih.gov
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 136-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219JX
UT WOS:000324503201791
ER

PT J
AU Uh, E
   Yang, XX
   Boshoff, HI
   Barry, CE
AF Uh, Eugene
   Yang, Xinxin
   Boshoff, Helena I.
   Barry, Clifton E., III
TI Aminopyrimidine kills Mycobacterium tuberculosis by inhibition of
   decaprenylphosphoryl-beta-d-ribose 2 '-epimerase
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 243rd National Spring Meeting of the American-Chemical-Society
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc
C1 [Uh, Eugene; Yang, Xinxin; Boshoff, Helena I.; Barry, Clifton E., III] NIAID, NIH, Bethesda, MD 20892 USA.
EM eugeneuh@gwmail.gwu.edu
NR 0
TC 0
Z9 0
U1 1
U2 1
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 MAR 25
PY 2012
VL 243
MA 393-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219JX
UT WOS:000324503202052
ER

PT J
AU Wang, YL
AF Wang, Yanli
TI Identifying druggable targets by mining open chemical biology data
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
   Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Wang, Yanli] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
EM ywang@ncbi.nlm.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 84-CINF
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475103414
ER

PT J
AU Weibel, DB
   Renner, LD
   Eswaramoorthy, P
   Krishnamurthy, K
AF Weibel, Douglas B.
   Renner, Lars D.
   Eswaramoorthy, Prahathees
   Krishnamurthy, Kumaran
TI Bacterial membrane curvature controls the formation of cardiolipin
   microdomains
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
   Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Weibel, Douglas B.; Renner, Lars D.] Univ Wisconsin, Madison, WI 53706 USA.
   [Eswaramoorthy, Prahathees; Krishnamurthy, Kumaran] NCI, NIH, Bethesda, MD 20892 USA.
EM weibel@biochem.wisc.edu
NR 0
TC 0
Z9 0
U1 0
U2 1
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 MAR 25
PY 2012
VL 243
MA 84-COLL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475103541
ER

PT J
AU Yancey, JA
   Biswas, P
   Vellore, NA
   Kucukkal, TG
   Collier, G
   Brooks, BR
   Stuart, SJ
   Latour, RA
AF Yancey, Jeremy A.
   Biswas, Pradip
   Vellore, Nadeem A.
   Kucukkal, Tugba G.
   Collier, Galen
   Brooks, Bernard R.
   Stuart, Steven J.
   Latour, Robert A.
TI Modeling multiphase systems with independent force fields controlling
   intra- and inter-phase interactions
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
   Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Yancey, Jeremy A.; Vellore, Nadeem A.; Collier, Galen; Latour, Robert A.] Clemson Univ, Dept Bioengn, Clemson, SC 29634 USA.
   [Kucukkal, Tugba G.; Stuart, Steven J.] Clemson Univ, Dept Chem, Clemson, SC 29634 USA.
   [Biswas, Pradip] Tougaloo Coll, Dept Phys, Tougaloo, MS 39174 USA.
   [Brooks, Bernard R.] NIH, Lab Computat Biol, Bethesda, MD 20892 USA.
EM jyancey@g.clemson.edu
RI Vellore, Nadeem/C-5763-2011
OI Vellore, Nadeem/0000-0003-4853-1508
NR 0
TC 0
Z9 0
U1 1
U2 1
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 MAR 25
PY 2012
VL 243
MA 121-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475104317
ER

PT J
AU Yong, KJ
   Baidoo, KE
   Milenic, DE
   Brechbiel, MW
AF Yong, Kwon J.
   Baidoo, Kwamena E.
   Milenic, Diane E.
   Brechbiel, Martin W.
TI Pb-212 radioimmunotherapy - observations along a lengthy long road
   forward
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 243rd National Spring Meeting of the American-Chemical-Society
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc
C1 [Yong, Kwon J.; Baidoo, Kwamena E.; Milenic, Diane E.; Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, Bethesda, MD 20892 USA.
EM martinwb@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 11-NUCL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219JX
UT WOS:000324503202124
ER

PT J
AU Yu, X
   Wang, QM
   Zhao, J
   Zhao, C
   Ma, BY
   Nussinov, R
   Zheng, J
AF Yu, Xiang
   Wang, Qiuming
   Zhao, Jun
   Zhao, Chao
   Ma, Buyong
   Nussinov, Ruth
   Zheng, Jie
TI Molecular structures of polymorphic amyloid-b oligomers
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
   Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Yu, Xiang; Wang, Qiuming; Zhao, Jun; Zhao, Chao; Zheng, Jie] Univ Akron, Dept Chem & Biomol Engn, Akron, OH 44325 USA.
   [Ma, Buyong; Nussinov, Ruth] SAIC Frederick Inc, Natl Canc Inst Frederick, Ctr Canc, Res Nanobiol Program, Frederick, MD 21702 USA.
EM yx13@zips.uakron.edu
RI Wang, Qiuming/E-6254-2014
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 38-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475104235
ER

PT J
AU Zhang, Y
   Louis, JM
   Sayer, JM
   Wang, YF
   Harrison, RW
   Weber, IT
AF Zhang, Ying
   Louis, John M.
   Sayer, Jane M.
   Wang, Yuan-Fang
   Harrison, Robert W.
   Weber, Irene T.
TI HIV-1 protease drug resistance mutant L76V exhibits decreased dimer
   stability and lower rate of autoprocessing via reduced internal
   hydrophobic contacts
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
   Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Zhang, Ying; Weber, Irene T.] Georgia State Univ, Dept Chem, Atlanta, GA 30303 USA.
   [Wang, Yuan-Fang; Harrison, Robert W.; Weber, Irene T.] Georgia State Univ, Dept Biol, Atlanta, GA 30303 USA.
   [Harrison, Robert W.] Georgia State Univ, Dept Comp Sci, Atlanta, GA 30303 USA.
   [Louis, John M.; Sayer, Jane M.] Natl Inst Diabet & Digest & Kidney Dis, Chem Phys Lab, NIH, Atlanta, GA 30303 USA.
EM yzhang20@student.gsu.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 82-BIOL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475100414
ER

PT J
AU Zhao, Q
   Gong, R
   Kumar, S
   Prabakaran, P
   Gehlsen, K
   Dimitrov, DS
AF Zhao, Qi
   Gong, Rui
   Kumar, Sandeep
   Prabakaran, Ponraj
   Gehlsen, Kurt
   Dimitrov, Dimiter S.
TI Novel antibody CH2-domain based binders to nucleolin: Isolation,
   characterization and improvement of stability and aggregation
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
   Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Zhao, Qi; Gong, Rui; Prabakaran, Ponraj; Dimitrov, Dimiter S.] NCI, Prot Interact Grp, Ctr Canc Res Nanobiol Program, NIH, Frederick, MD 21702 USA.
   [Kumar, Sandeep] Pfizer Inc, BioTherapeut Pharmaceut Sci, St Louis, MO 63017 USA.
   [Prabakaran, Ponraj] Sci Applicat Int Corp Frederick Inc, Basic Res Program, Frederick, MD 21702 USA.
   [Gehlsen, Kurt] Res Corp Technol Inc, Tucson, AZ USA.
EM dimiter.dimitrov@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 195-BIOT
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475100730
ER

PT J
AU Zhao, XZ
   Maddali, K
   Smith, SJ
   Metifiot, M
   Hare, S
   Marchand, C
   Cherepanov, P
   Hughes, SH
   Pommier, Y
   Burke, TR
AF Zhao, Xue Zhi
   Maddali, Kasthuraiah
   Smith, Steven J.
   Metifiot, Mathieu
   Hare, Stephen
   Marchand, Christophe
   Cherepanov, Peter
   Hughes, Stephen H.
   Pommier, Yves
   Burke, Terrence R., Jr.
TI 6,7-Dihydroxy-1-oxoisoindoline-4-sulfonamide-containing HIV-1 integrase
   inhibitors
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 243rd National Spring Meeting of the American-Chemical-Society
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc
C1 [Zhao, Xue Zhi; Burke, Terrence R., Jr.] NCI, NIH, Biol Chem Lab, Frederick, MD 21702 USA.
   [Maddali, Kasthuraiah; Metifiot, Mathieu; Marchand, Christophe; Pommier, Yves] NCI, NIH, Mol Pharmacol Lab, Betheada, MD 20892 USA.
   [Smith, Steven J.; Hughes, Stephen H.] NCI, NIH, HIV Drug Resistance Program, Frederick, MD 21702 USA.
   [Hare, Stephen; Cherepanov, Peter] Univ London Imperial Coll Sci Technol & Med, Div Infect Dis, London, England.
EM zhaoxue@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 MAR 25
PY 2012
VL 243
MA 171-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219JX
UT WOS:000324503201825
ER

PT J
AU Zheng, J
   Zhao, J
   Yu, X
   Jang, H
   Nussinov, R
AF Zheng, Jie
   Zhao, Jun
   Yu, Xiang
   Jang, Hyunbum
   Nussinov, Ruth
TI Amyloid ion channels: Selective or non-selective channel?
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
   Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Zheng, Jie; Zhao, Jun; Yu, Xiang] Univ Akron, Dept Chem & Biomol Engn, Akron, OH 44325 USA.
   [Jang, Hyunbum; Nussinov, Ruth] NCI, Ctr Canc Res Nanobiol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
EM zhengj@uakron.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 232-BIOT
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475100765
ER

PT J
AU Zhu, FQ
   Hummer, G
AF Zhu, Fangqiang
   Hummer, Gerhard
TI Water in ion channel gating
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 243rd National Spring Meeting of the American-Chemical-Society
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc
C1 [Zhu, Fangqiang; Hummer, Gerhard] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM gerhard.hummer@nih.gov
RI Hummer, Gerhard/A-2546-2013
OI Hummer, Gerhard/0000-0001-7768-746X
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR 25
PY 2012
VL 243
MA 91-PHYS
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219JX
UT WOS:000324503203341
ER

PT J
AU Chen, XH
   Peer, CJ
   Alfaro, R
   Tian, T
   Spencer, SD
   Figg, WD
AF Chen, Xiaohong
   Peer, Cody J.
   Alfaro, Raul
   Tian, Tian
   Spencer, Shawn D.
   Figg, William D.
TI Quantification of irinotecan, SN38, and SN38G in human and porcine
   plasma by ultra high-performance liquid chromatography-tandem mass
   spectrometry and its application to hepatic chemoembolization
SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
LA English
DT Article
DE Irinotecan; SN38; Camptothecin; Mass spectrometry; Ultra-high
   performance liquid chromatography
ID ACTIVE METABOLITE SN-38; DRUG ELUTING BEADS; CAMPTOTHECIN DERIVATIVE
   IRINOTECAN; FLUORESCENCE DETECTION; LIVER METASTASES;
   7-ETHYL-10-HYDROXYCAMPTOTHECIN SN-38; COLORECTAL-CANCER; MAJOR
   METABOLITES; CARBOXYLATE FORMS; LACTONE FORMS
AB An analytical method was developed and validated for the quantitative determination of irinotecan, its active metabolite SN38, and glucuronidated SN38 (SN38-G) in both porcine and human plasma. Calibration curves were linear within the concentration range of 0.5-100 ng/mL for SN38 and SN38-G, and 5-1000 ng/mL for irinotecan. Sample pretreatment involved solid-phase extraction of 0.1 mL aliquots of plasma. Irinotecan, SN38, SN38-G, and the internal standards, irinotecan-d10, tolbutamide, and camptothecin, respectively, were separated on a Waters ACQUITY UPLC (TM) BEH RP18 column (2.1 mm x 50 mm, 1.7 mu m), using a mobile phase composed of methanol and 0.1% formic acid. Accuracy of quality control samples in human plasma ranged from 98.5 to 110.3%, 99.5 to 101.7% and 96.2 to 98.9% for irinotecan, SN38, and SN38-G, respectively. Precision of the three analytes in the same order ranged from 0.8 to 2.8%, 2.4 to 5.7%, and 2.4 to 2.8%. All three analytes proved stable in plasma through four freeze/thaw cycles, as well as through 6 h in whole blood at room temperature. The method was likewise validated in porcine plasma with comparable accuracies and precisions also within the generally acceptable range. The validated method was applied to both preclinical and clinical trials involving hepatic chemoembolization of irinotecan drug-eluting beads to study the pharmacokinetics of the three analytes. Published by Elsevier B.V.
C1 [Figg, William D.] NCI, Clin Pharmacol Program, NIH, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Chen, Xiaohong; Spencer, Shawn D.] NCI, Clin Pharmacol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
   [Alfaro, Raul] NIH, Pharm Sect, Ctr Clin, Bethesda, MD 20892 USA.
RP Figg, WD (reprint author), NCI, Clin Pharmacol Program, NIH, Ctr Canc Res, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA.
EM wdfigg@helix.nih.gov
RI Figg Sr, William/M-2411-2016
FU National Cancer Institute, National Institutes of Health
   [HHSN261200800001E]; Center for Cancer Research, National Cancer
   Institute, National Institutes of Health
FX This project has been funded in whole or in part with federal funds from
   the National Cancer Institute, National Institutes of Health, as well as
   the Intramural Research Program of the Center for Cancer Research,
   National Cancer Institute, National Institutes of Health. Some authors
   are affiliated with the SAIC Frederick, Inc., with federal funds from
   the National Cancer Institute, National Institutes of Health, under
   Contract No. HHSN261200800001E.
NR 36
TC 13
Z9 13
U1 0
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0731-7085
J9 J PHARMACEUT BIOMED
JI J. Pharm. Biomed. Anal.
PD MAR 25
PY 2012
VL 62
BP 140
EP 148
DI 10.1016/j.jpba.2012.01.008
PG 9
WC Chemistry, Analytical; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 902IQ
UT WOS:000301032200018
PM 22305081
ER

PT J
AU Swinburn, B
   Hall, KD
AF Swinburn, Boyd
   Hall, Kevin D.
TI Diet composition and obesity reply
SO LANCET
LA English
DT Letter
C1 [Hall, Kevin D.] NIDDK, NIH, Bethesda, MD 20892 USA.
   [Swinburn, Boyd] Deakin Univ, WHO Collaborating Ctr Obes Prevent, Melbourne, Vic, Australia.
RP Hall, KD (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA.
EM kevinh@niddk.nih.gov
NR 4
TC 1
Z9 1
U1 0
U2 6
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 MAR 24
PY 2012
VL 379
IS 9821
BP 1100
EP 1101
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 916VR
UT WOS:000302131800025
ER

PT J
AU Archer, J
   Baillie, G
   Watson, SJ
   Kellam, P
   Rambaut, A
   Robertson, DL
AF Archer, John
   Baillie, Greg
   Watson, Simon J.
   Kellam, Paul
   Rambaut, Andrew
   Robertson, David L.
TI Analysis of high-depth sequence data for studying viral diversity: a
   comparison of next generation sequencing platforms using Segminator II
SO BMC BIOINFORMATICS
LA English
DT Article
ID HIV-1 DRUG-RESISTANCE; HIGH-THROUGHPUT; SNP DISCOVERY; VARIANTS;
   QUALITY; READS; BIOINFORMATICS; ALIGNMENT; MINORITY; ACCURACY
AB Background: Next generation sequencing provides detailed insight into the variation present within viral populations, introducing the possibility of treatment strategies that are both reactive and predictive. Current software tools, however, need to be scaled up to accommodate for high-depth viral data sets, which are often temporally or spatially linked. In addition, due to the development of novel sequencing platforms and chemistries, each with implicit strengths and weaknesses, it will be helpful for researchers to be able to routinely compare and combine data sets from different platforms/chemistries. In particular, error associated with a specific sequencing process must be quantified so that true biological variation may be identified.
   Results: Segminator II was developed to allow for the efficient comparison of data sets derived from different sources. We demonstrate its usage by comparing large data sets from 12 influenza H1N1 samples sequenced on both the 454 Life Sciences and Illumina platforms, permitting quantification of platform error. For mismatches median error rates at 0.10 and 0.12%, respectively, suggested that both platforms performed similarly. For insertions and deletions median error rates within the 454 data (at 0.3 and 0.2%, respectively) were significantly higher than those within the Illumina data (0.004 and 0.006%, respectively). In agreement with previous observations these higher rates were strongly associated with homopolymeric stretches on the 454 platform. Outside of such regions both platforms had similar indel error profiles. Additionally, we apply our software to the identification of low frequency variants.
   Conclusion: We have demonstrated, using Segminator II, that it is possible to distinguish platform specific error from biological variation using data derived from two different platforms. We have used this approach to quantify the amount of error present within the 454 and Illumina platforms in relation to genomic location as well as location on the read. Given that next generation data is increasingly important in the analysis of drug-resistance and vaccine trials, this software will be useful to the pathogen research community. A zip file containing the source code and jar file is freely available for download from http://www.bioinf.manchester.ac.uk/segminator/.
C1 [Archer, John; Robertson, David L.] Univ Manchester, Fac Life Sci, Manchester, Lancs, England.
   [Baillie, Greg; Watson, Simon J.; Kellam, Paul] Wellcome Trust Sanger Inst, Cambridge, England.
   [Kellam, Paul] UCL, Div Infect & Immun, UCL MRC Ctr Med Mol Virol, London, England.
   [Rambaut, Andrew] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh, Midlothian, Scotland.
   [Rambaut, Andrew] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Archer, J (reprint author), Univ Manchester, Fac Life Sci, Manchester, Lancs, England.
EM john.archer@manchester.ac.uk; david.robertson@manchester.ac.uk
RI Baillie, Gregory/F-9478-2013; 
OI Baillie, Gregory/0000-0002-6130-250X; Archer, John/0000-0001-6212-0962;
   Rambaut, Andrew/0000-0003-4337-3707
FU BBSRC [BB/H012419/1]
FX We wish to thank BBSRC for funding, project grant: BB/H012419/1. We also
   wish to thank Felix Feyertag, Bram Vrancken and Kenneth Henry for useful
   discussion.
NR 38
TC 40
Z9 40
U1 2
U2 20
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 MAR 23
PY 2012
VL 13
AR 47
DI 10.1186/1471-2105-13-47
PG 11
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
   Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Mathematical & Computational Biology
GA 946JU
UT WOS:000304348700001
PM 22443413
ER

PT J
AU Xiao, TS
   Tine, JPY
AF Xiao, Tsan Sam
   Tine, Jenny P. -Y.
TI NLRX1 Has a Tail to Tell
SO IMMUNITY
LA English
DT Editorial Material
ID OXYGEN SPECIES PRODUCTION; NF-KAPPA-B; MITOCHONDRIAL; INFECTION;
   PATHWAYS; MAVS
AB In this issue of Immunity, Hong et al. (2012) report the first structural analysis of the C-terminal fragment of an NLR (nucleotide-binding domain [NBD] and leucine-rich repeat [LRR]-containing) protein, NLRX1. This fragment forms a hexamer and binds RNA.
C1 [Xiao, Tsan Sam] NIAID, Struct Immunobiol Unit, Immunol Lab, NIH, Bethesda, MD 20892 USA.
   [Tine, Jenny P. -Y.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Ctr Translat Immunol, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA.
   [Tine, Jenny P. -Y.] Inflammatory Dis Inst, Chapel Hill, NC 27599 USA.
RP Xiao, TS (reprint author), NIAID, Struct Immunobiol Unit, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM xiaot@niaid.nih.gov; jenny_ting@med.unc.edu
RI Xiao, Tsan/I-7616-2013; Xiao, Tsan/A-8590-2010
OI Xiao, Tsan/0000-0001-9688-475X; 
FU Intramural NIH HHS [ZIA AI000960-07]; NCI NIH HHS [R01 CA156330]; NIAID
   NIH HHS [U54 AI057157]
NR 10
TC 5
Z9 5
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD MAR 23
PY 2012
VL 36
IS 3
BP 311
EP 312
DI 10.1016/j.immuni.2012.03.002
PG 2
WC Immunology
SC Immunology
GA 915ST
UT WOS:000302048400001
PM 22444625
ER

PT J
AU Migueles, SA
   Connors, M
AF Migueles, Stephen A.
   Connors, Mark
TI Small Molecules and Big Killers: The Challenge of Eliminating the Latent
   HIV Reservoir
SO IMMUNITY
LA English
DT Editorial Material
ID INFECTION
AB In this issue of Immunity, Shan et al. (2012) explore the elimination of cells latently infected with HIV and the potential implications for strategies to eradicate the virus from infected patients.
C1 [Migueles, Stephen A.; Connors, Mark] NIAID, HIV Specif Immun Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Connors, M (reprint author), NIAID, HIV Specif Immun Sect, Immunoregulat Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM mconnors@nih.gov
NR 10
TC 6
Z9 6
U1 0
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD MAR 23
PY 2012
VL 36
IS 3
BP 320
EP 321
DI 10.1016/j.immuni.2012.03.006
PG 2
WC Immunology
SC Immunology
GA 915ST
UT WOS:000302048400005
PM 22444629
ER

PT J
AU Geng, H
   Sakato, M
   DeRocco, V
   Yamane, K
   Du, CW
   Erie, DA
   Hingorani, M
   Hsieh, P
AF Geng, Hui
   Sakato, Miho
   DeRocco, Vanessa
   Yamane, Kazuhiko
   Du, Chunwei
   Erie, Dorothy A.
   Hingorani, Manju
   Hsieh, Peggy
TI Biochemical Analysis of the Human Mismatch Repair Proteins hMutS alpha
   MSH2(G674A)-MSH6 and MSH2-MSH6(T1219D)
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID SACCHAROMYCES-CEREVISIAE MSH2-MSH6; NUCLEOTIDE-BINDING SITES; HUMAN
   NUCLEAR EXTRACTS; MUTL-ALPHA; DNA-REPAIR; DOMINANT MUTATIONS;
   MISPAIR-BINDING; ATR KINASE; COMPLEX; MSH2
AB The heterodimeric human MSH2-MSH6 protein initiates DNA mismatch repair (MMR) by recognizing mismatched bases that result from replication errors. Msh2(G674A) or Msh6(T1217D) mice that have mutations in or near the ATP binding site of MSH2 or ATP hydrolysis catalytic site of MSH6 develop cancer and have a reduced lifespan due to loss of the MMR pathway (Lin, D. P., Wang, Y., Scherer, S. J., Clark, A. B., Yang, K., Avdievich, E., Jin, B., Werling, U., Parris, T., Kurihara, N., Umar, A., Kucherlapati, R., Lipkin, M., Kunkel, T. A., and Edelmann, W. (2004) Cancer Res. 64, 517522; Yang, G., Scherer, S. J., Shell, S. S., Yang, K., Kim, M., Lipkin, M., Kucherlapati, R., Kolodner, R. D., and Edelmann, W. (2004) Cancer Cell 6, 139150). Mouse embryonic fibroblasts from these mice retain an apoptotic response to DNA damage. Mutant human MutS alpha proteins MSH2(G674A)-MSH6(wt) and MSH2(wt)-MSH6T(1219D) are profiled in a variety of functional assays and as expected fail to support MMR in vitro, although they retain mismatch recognition activity. Kinetic analyses of DNA binding and ATPase activities and examination of the excision step of MMR reveal that the two mutants differ in their underlying molecular defects. MSH2(wt)-MSH6(T1219D) fails to couple nucleotide binding and mismatch recognition, whereas MSH2(G674A)-MSH6(wt) has a partial defect in nucleotide binding. Nevertheless, both mutant proteins remain bound to the mismatch and fail to promote efficient excision thereby inhibiting MMR in vitro in a dominant manner. Implications of these findings for MMR and DNA damage signaling by MMR proteins are discussed.
C1 [Geng, Hui; Yamane, Kazuhiko; Du, Chunwei; Hsieh, Peggy] NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA.
   [Sakato, Miho; Hingorani, Manju] Wesleyan Univ, Dept Mol Biol & Biochem, Middletown, CT 06459 USA.
   [DeRocco, Vanessa; Erie, Dorothy A.] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA.
RP Hsieh, P (reprint author), 9000 Rockville Pike,5 Mem Dr,MSC 0538,Bldg 5 Rm 3, Bethesda, MD 20892 USA.
EM peggyh@intra.niddk.nih.gov
FU National Institutes of Health of NIDDK [F31 GM087096, GM 079480]; State
   of Connecticut Department of Public Health [2011-0138]
FX This work was supported, in whole or in part, by the National Institutes
   of Health Intramural Research Program of NIDDK (to H. G., C. D., K.Y.,
   and P. H.) and Grants F31 GM087096 (to V. R.) and GM 079480 (to D. A.
   E.). This work was also supported by State of Connecticut Department of
   Public Health Grant 2011-0138 (to M.H.).
NR 54
TC 11
Z9 11
U1 0
U2 10
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 MAR 23
PY 2012
VL 287
IS 13
BP 9777
EP 9791
DI 10.1074/jbc.M111.316919
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 917IN
UT WOS:000302167200011
PM 22277660
ER

PT J
AU Fujimoto, K
   Matsuura, K
   Hu-Wang, E
   Lu, R
   Shi, YB
AF Fujimoto, Kenta
   Matsuura, Kazuo
   Hu-Wang, Eileen
   Lu, Rosemary
   Shi, Yun-Bo
TI Thyroid Hormone Activates Protein Arginine Methyltransferase 1
   Expression by Directly Inducing c-Myc Transcription during Xenopus
   Intestinal Stem Cell Development
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID AMPHIBIAN METAMORPHOSIS; POSTEMBRYONIC DEVELOPMENT; EPITHELIAL
   DEVELOPMENT; RECEPTOR SUPERFAMILY; GENE REPRESSION; TR-ALPHA; LAEVIS;
   BETA; RECRUITMENT; FROG
AB Adult organ-specific stem cells are essential for organ homeostasis and tissue repair and regeneration. The formation of such stem cells during vertebrate development is poorly understood. Intestinal remodeling during thyroid hormone (T3)-dependent Xenopus metamorphosis resembles postembryonic intestinal maturation in mammals. During metamorphosis, the intestine is remodeled de novo via a yet unknown mechanism. Protein arginine methyltransferase 1 (PRMT1) is up-regulated in and required for adult intestinal stem cells during metamorphosis. PRMT1 up-regulation is the earliest known molecular event for the developing stem cells and is also conserved during zebrafish and mouse intestinal development. To analyze how PRMT1 is specifically up-regulated during the formation of the adult intestinal stem cells, wecloned the Xenopus PRMT1 promoter and characterized it in CaCo-2 cells, a human cell line with intestinal stem cell characteristics. Through a series deletion and mutational analyses, we showed that the stem cell-associated transcription factor c-Myc could bind to a conserved site in the first intron to activate the promoter. Furthermore, we demonstrated that during metamorphosis, both c-Myc and PRMT1 were highly up-regulated, specifically in the remodeling intestine but not the resorbing tail, and that c-Myc was induced by T3 prior to PRMT1 up-regulation. In addition, we showed that T3 directly activated the c-Myc gene during metamorphosis in the intestine via binding of the T3 receptor to the c-Myc promoter. These results suggest that T3 induces c-Myc transcription directly in the intestine, that c-Myc, in turn, activates PRMT1 expression, and that this is an important gene regulation cascade controlling intestinal stem cell development.
C1 [Fujimoto, Kenta; Matsuura, Kazuo; Hu-Wang, Eileen; Lu, Rosemary; Shi, Yun-Bo] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Morphogenesis, Lab Gene Regulat & Dev, PCRM,NIH, Bethesda, MD 20892 USA.
RP Shi, YB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Morphogenesis, Lab Gene Regulat & Dev, PCRM,NIH, Bethesda, MD 20892 USA.
EM Shi@helix.nih.gov
FU NICHD, National Institutes of Health; Japan Society for the Promotion of
   Sciences (NIH)
FX This work was supported, in whole or in part, by the NICHD, National
   Institutes of Health intramural research program. This work was also
   supported by a fellowship by the Japan Society for the Promotion of
   Sciences (NIH) (to K. F.). This work was also supported by a Fellowship
   for Japanese Biochemical and Behavioral Researchers at NIH from Japan
   Society for the Promotion of Science (to K. F.).
NR 77
TC 10
Z9 12
U1 0
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAR 23
PY 2012
VL 287
IS 13
BP 10039
EP 10050
DI 10.1074/jbc.M111.335661
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 917IN
UT WOS:000302167200036
PM 22315222
ER

PT J
AU Arakaki, M
   Ishikawa, M
   Nakamura, T
   Iwamoto, T
   Yamada, A
   Fukumoto, E
   Saito, M
   Otsu, K
   Harada, H
   Yamada, Y
   Fukumoto, S
AF Arakaki, Makiko
   Ishikawa, Masaki
   Nakamura, Takashi
   Iwamoto, Tsutomu
   Yamada, Aya
   Fukumoto, Emiko
   Saito, Masahiro
   Otsu, Keishi
   Harada, Hidemitsu
   Yamada, Yoshihiko
   Fukumoto, Satoshi
TI Role of Epithelial-Stem Cell Interactions during Dental Cell
   Differentiation
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID TOOTH MORPHOGENESIS; IN-VIVO; FACTOR EPIPROFIN; DEFINED FACTORS; NEURAL
   CREST; EXPRESSION; TEETH; PLURIPOTENT; INDUCTION; PULP
AB Epithelial-mesenchymal interactions regulate the growth and morphogenesis of ectodermal organs such as teeth. Dental pulp stem cells (DPSCs) are a part of dental mesenchyme, derived from the cranial neural crest, and differentiate into dentin forming odontoblasts. However, the interactions between DPSCs and epithelium have not been clearly elucidated. In this study, we established a mouse dental pulp stem cell line (SP) comprised of enriched side population cells that displayed a multipotent capacity to differentiate into odontogenic, osteogenic, adipogenic, and neurogenic cells. We also analyzed the interactions between SP cells and cells from the rat dental epithelial SF2 line. When cultured with SF2 cells, SP cells differentiated into odontoblasts that expressed dentin sialophosphoprotein. This differentiation was regulated by BMP2 and BMP4, and inhibited by the BMP antagonist Noggin. We also found that mouse iPS cells cultured with mitomycin C-treated SF2-24 cells displayed an epithelial cell-like morphology. Those cells expressed the epithelial cell markers p63 and cytokeratin-14, and the ameloblast markers ameloblastin and enamelin, whereas they did not express the endodermal cell marker Gata6 or mesodermal cell marker brachyury. This is the first report of differentiation of iPS cells into ameloblasts via interactions with dental epithelium. Co-culturing with dental epithelial cells appears to induce stem cell differentiation that favors an odontogenic cell fate, which may be a useful approach for tooth bioengineering strategies.
C1 [Arakaki, Makiko; Nakamura, Takashi; Iwamoto, Tsutomu; Yamada, Aya; Fukumoto, Emiko; Fukumoto, Satoshi] Tohoku Univ, Dept Oral Hlth & Dev Sci, Grad Sch Dent, Div Pediat Dent, Sendai, Miyagi 9808575, Japan.
   [Ishikawa, Masaki; Yamada, Yoshihiko] NIDCR, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
   [Saito, Masahiro] Tokyo Univ Sci, Fac Ind Sci & Technol, Chiba 2788510, Japan.
   [Otsu, Keishi; Harada, Hidemitsu] Iwate Med Coll, Sch Dent, Dept Oral Anat 2, Morioka, Iwate 0208505, Japan.
RP Fukumoto, S (reprint author), Tohoku Univ, Dept Oral Hlth & Dev Sci, Grad Sch Dent, Div Pediat Dent, Sendai, Miyagi 9808575, Japan.
EM fukumoto@dent.tohoku.ac.jp
RI Nakamura, Takashi/P-7796-2016
OI Nakamura, Takashi/0000-0001-9904-1037
FU NIDCR, National Institutes of Health; Ministry of Education, Science,
   and Culture of Japan [20679006, 21792054, 21792154]; NEXT program
   [LS010]; Takeda Science Foundation
FX This work was supported, in whole or in part, by the Intramural Research
   Program of the NIDCR, National Institutes of Health (to Y. Y.). This
   work was also supported by Grants-in-aid 20679006 (to S. F.), 21792054
   (to A. Y.), 21792154 (to E. F.) from the Ministry of Education, Science,
   and Culture of Japan, and the NEXT program (LS010, to S. F.), and by
   grants from the Takeda Science Foundation.
NR 42
TC 37
Z9 40
U1 1
U2 18
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 MAR 23
PY 2012
VL 287
IS 13
BP 10590
EP 10601
DI 10.1074/jbc.M111.285874
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 917IN
UT WOS:000302167200084
PM 22298769
ER

PT J
AU Fleming, JM
   Ginsburg, E
   Goldhar, AS
   Plant, J
   Vonderhaar, BK
AF Fleming, Jodie M.
   Ginsburg, Erika
   Goldhar, Anita S.
   Plant, Joshua
   Vonderhaar, Barbara K.
TI Progesterone Receptor Activates Msx2 Expression by Downregulating
   TNAP/Akp2 and Activating the Bmp Pathway in EpH4 Mouse Mammary
   Epithelial Cells
SO PLOS ONE
LA English
DT Article
ID BREAST-CANCER CELLS; HORMONE REPLACEMENT THERAPY; MESENCHYMAL
   TRANSITION; GLAND DEVELOPMENT; BONE METASTASIS; GENE-REGULATION;
   ESTROGEN; GROWTH; PROLIFERATION; ALK2
AB Previously we demonstrated that EpH4 mouse mammary epithelial cells induced the homeobox transcription factor Msx2 either when transfected with the progesterone receptor (PR) or when treated with Bmp2/4. Msx2 upregulation was unaffected by Wnt inhibitors s-FRP or Dkk1, but was inhibited by the Bmp antagonist Noggin. We therefore hypothesized that PR signaling to Msx2 acts through the Bmp receptor pathway. Herein, we confirm that transcripts for Alk2/ActR1A, a non-canonical BmpR Type I, are upregulated in mammary epithelial cells overexpressing PR (EpH4-PR). Increased phosphorylation of Smads 1,5, 8, known substrates for Alk2 and other BmpR Type I proteins, was observed as was their translocation to the nucleus in EpH4-PR cells. Analysis also showed that Tissue Non-Specific Alkaline Phosphatase (TNAP/Akp2) was also found to be downregulated in EpH4-PR cells. When an Akp2 promoter-reporter construct containing a 1/2PRE site was transfected into EpH4-PR cells, its expression was downregulated. Moreover, siRNA mediated knockdown of Akp2 increased both Alk2 and Msx2 expression. Collectively these data suggest that PR inhibition of Akp2 results in increased Alk2 activity, increased phosphorylation of Smads 1,5,8, and ultimately upregulation of Msx2. These studies imply that reactivation of the Akp2 gene could be helpful in downregulating aberrant Msx2 expression in PR+ breast cancers.
C1 [Fleming, Jodie M.; Ginsburg, Erika; Goldhar, Anita S.; Plant, Joshua; Vonderhaar, Barbara K.] NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Fleming, Jodie M.] N Carolina Cent Univ, Dept Biol, Durham, NC USA.
RP Fleming, JM (reprint author), NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
EM ginsbure@mail.nih.gov
FU NCI NIH HHS [SC2 CA176585]
NR 46
TC 1
Z9 1
U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 22
PY 2012
VL 7
IS 3
AR e34058
DI 10.1371/journal.pone.0034058
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 940QX
UT WOS:000303909200041
PM 22457812
ER

PT J
AU Nader, N
   Ng, SSM
   Wang, YH
   Abel, BS
   Chrousos, GP
   Kino, T
AF Nader, Nancy
   Ng, Sinnie Sin Man
   Wang, Yonghong
   Abel, Brent S.
   Chrousos, George P.
   Kino, Tomoshige
TI Liver X Receptors Regulate the Transcriptional Activity of the
   Glucocorticoid Receptor: Implications for the Carbohydrate Metabolism
SO PLOS ONE
LA English
DT Article
ID PHOSPHOENOLPYRUVATE CARBOXYKINASE GENE; POTENTIAL CLINICAL-IMPLICATIONS;
   RESPONSE ELEMENTS; ESTROGEN-RECEPTOR; NUCLEAR RECEPTORS;
   LIPID-METABOLISM; ACCESSORY FACTOR; LXR-ALPHA; RAT-LIVER; EXPRESSION
AB GLUCOCORTICOIDS are steroid hormones that strongly influence intermediary carbohydrate metabolism by increasing the transcription rate of glucose-6-phosphatase (G6Pase), a key enzyme of gluconeogenesis, and suppress the immune system through the glucocorticoid receptor (GR). The liver X receptors (LXRs), on the other hand, bind to cholesterol metabolites, heterodimerize with the retinoid X receptor (RXR), and regulate the cholesterol turnover, the hepatic glucose metabolism by decreasing the expression of G6Pase, and repress a set of inflammatory genes in immune cells. Since the actions of these receptors overlap with each other, we evaluated the crosstalk between the GR- and LXR-mediated signaling systems. Transient transfection-based reporter assays and gene silencing methods using siRNAs for LXRs showed that overexpression/ligand (GW3965) activation of LXRs/RXRs repressed GR- stimulated transactivation of certain glucocorticoid response element (GRE)-driven promoters in a gene-specific fashion. Activation of LXRs by GW3965 attenuated dexamethasone-stimulated elevation of circulating glucose in rats. It also suppressed dexamethasone-induced mRNA expression of hepatic glucose-6-phosphatase (G6Pase) in rats, mice and human hepatoma HepG2 cells, whereas endogenous, unliganded LXRs were required for dexamethasone-induced mRNA expression of phosphoenolpyruvate carboxylase. In microarray transcriptomic analysis of rat liver, GW3965 differentially regulated glucocorticoid-induced transcriptional activity of about 15% of endogenous glucocorticoid-responsive genes. To examine the mechanism through which activated LXRs attenuated GR transcriptional activity, we examined LXR alpha/RXR alpha binding to GREs. Endogenous LXR alpha/RXR alpha bound GREs and inhibited GR binding to these DNA sequences both in in vitro and in vivo chromatin immunoprecipitation assays, while their recombinant proteins did so on classic or G6Pase GREs in gel mobility shift assays. We propose that administration of LXR agonists may be beneficial in glucocorticoid treatment- or stress-associated dysmetabolic states by directly and gene-specifically attenuating the transcriptional activity of the GR on glucose and/or lipid metabolism.
C1 [Nader, Nancy; Ng, Sinnie Sin Man; Abel, Brent S.; Kino, Tomoshige] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Mol Hormone Act, Program Reprod & Adult Endocrinol, Natl Inst Hlth, Bethesda, MD USA.
   [Ng, Sinnie Sin Man] Chinese Univ Hong Kong, Sch Biomed Sci, Fac Med, Shatin, Hong Kong, Peoples R China.
   [Ng, Sinnie Sin Man] Hong Kong Special Adm Reg, Hong Kong, Hong Kong, Peoples R China.
   [Wang, Yonghong] Natl Canc Inst, Adv Technol Ctr, Natl Inst Hlth, Gaithersburg, MD USA.
   [Chrousos, George P.] Univ Athens, Sch Med, Dept Pediat 1, GR-11527 Athens, Greece.
RP Nader, N (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Mol Hormone Act, Program Reprod & Adult Endocrinol, Natl Inst Hlth, Bethesda, MD USA.
EM nadernancy@hotmail.com
FU Eunice Kennedy Shriver National Institute of Child Health and Human
   Development, National Institutes of Health
FX This study was funded by the Intramural Research Program of the Eunice
   Kennedy Shriver National Institute of Child Health and Human
   Development, National Institutes of Health. The funders had no role in
   study design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
NR 56
TC 17
Z9 17
U1 0
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 22
PY 2012
VL 7
IS 3
AR e26751
DI 10.1371/journal.pone.0026751
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 940QX
UT WOS:000303909200001
PM 22457708
ER

PT J
AU Kozak, CA
AF Kozak, Christine A.
TI Viewpoint on Emv2, the onlhy endogenous ecotropic murine leukemia virus
   of C57BL/6 mice
SO RETROVIROLOGY
LA English
DT Editorial Material
ID STRAINS; GENES
AB Here I comment on the articles by Lee and colleagues (Retrovirology 2011, 8: 82) and Lee and Cho (Retrovirology 2012, 9: 23) dealing with an endogenous ecotropic mouse leukemia virus found in C57BL mice.
C1 NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA.
RP Kozak, CA (reprint author), NIAID, Mol Microbiol Lab, Bldg 4,Room 329,4 Ctr Dr,MSC 0460, Bethesda, MD 20892 USA.
EM ckozak@niaid.nih.gov
NR 13
TC 2
Z9 2
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4690
J9 RETROVIROLOGY
JI Retrovirology
PD MAR 22
PY 2012
VL 9
AR 25
DI 10.1186/1742-4690-9-25
PG 2
WC Virology
SC Virology
GA 933RG
UT WOS:000303379200001
PM 22439739
ER

PT J
AU Kochenderfer, JN
   Dudley, ME
   Feldman, SA
   Wilson, WH
   Spaner, DE
   Maric, I
   Stetler-Stevenson, M
   Phan, GQ
   Hughes, MS
   Sherry, RM
   Yang, JC
   Kammula, US
   Devillier, L
   Carpenter, R
   Nathan, DAN
   Morgan, RA
   Laurencot, C
   Rosenberg, SA
AF Kochenderfer, James N.
   Dudley, Mark E.
   Feldman, Steven A.
   Wilson, Wyndham H.
   Spaner, David E.
   Maric, Irina
   Stetler-Stevenson, Maryalice
   Phan, Giao Q.
   Hughes, Marybeth S.
   Sherry, Richard M.
   Yang, James C.
   Kammula, Udai S.
   Devillier, Laura
   Carpenter, Robert
   Nathan, Debbie-Ann N.
   Morgan, Richard A.
   Laurencot, Carolyn
   Rosenberg, Steven A.
TI B-cell depletion and remissions of malignancy along with
   cytokine-associated toxicity in a clinical trial of anti-CD19
   chimeric-antigen-receptor-transduced T cells
SO BLOOD
LA English
DT Article
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; HIGH-DOSE
   INTERLEUKIN-2; NON-HODGKIN-LYMPHOMA; PHASE-I TRIAL; ANTITUMOR-ACTIVITY;
   ADOPTIVE IMMUNOTHERAPY; MONOCLONAL-ANTIBODY; CANCER-PATIENTS; ADVERSE
   EVENT
AB We conducted a clinical trial to assess adoptive transfer of T cells genetically modified to express an anti-CD19 chimeric Ag receptor (CAR). Our clinical protocol consisted of chemotherapy followed by an infusion of anti-CD19-CAR-transduced T cells and a course of IL-2. Six of the 8 patients treated on our protocol obtained remissions of their advanced, progressive B-cell malignancies. Four of the 8 patients treated on the protocol had long-term depletion of normal polyclonal CD19(+) B-lineage cells. Cells containing the anti-CD19 CAR gene were detected in the blood of all patients. Four of the 8 treated patients had prominent elevations in serum levels of the inflammatory cytokines IFN gamma and TNF. The severity of acute toxicities experienced by the patients correlated with serum IFN gamma and TNF levels. The infused anti-CD19-CAR-transduced T cells were a possible source of these inflammatory cytokines because we demonstrated peripheral blood T cells that produced TNF and IFN gamma ex vivo in a CD19-specific manner after anti-CD19-CAR-transduced T-cell infusions. Anti-CD19-CAR-transduced T cells have great promise to improve the treatment of B-cell malignancies because of a potent ability to eradicate CD19(+) cells in vivo; however, reversible cytokine-associated toxicities occurred after CAR-transduced T-cell infusions. This trial was registered with ClinicalTrials.gov as NCT00924326. (Blood. 2012; 119(12): 2709-2720)
C1 [Kochenderfer, James N.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
   [Dudley, Mark E.; Feldman, Steven A.; Phan, Giao Q.; Hughes, Marybeth S.; Sherry, Richard M.; Yang, James C.; Kammula, Udai S.; Devillier, Laura; Nathan, Debbie-Ann N.; Morgan, Richard A.; Laurencot, Carolyn; Rosenberg, Steven A.] NCI, Surg Branch, Bethesda, MD 20892 USA.
   [Wilson, Wyndham H.] NCI, Metab Branch, Bethesda, MD 20892 USA.
   [Spaner, David E.] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada.
   [Maric, Irina] NIH, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA.
   [Stetler-Stevenson, Maryalice] NCI, Pathol Lab, Bethesda, MD 20892 USA.
RP Kochenderfer, JN (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, 10 Ctr Dr,CRC Rm 3-3330, Bethesda, MD 20892 USA.
EM kochendj@mail.nih.gov
FU Center for Cancer Research, National Cancer Institute, National
   Institutes of Health
FX This work was supported by intramural funding of the Center for Cancer
   Research, National Cancer Institute, National Institutes of Health.
NR 50
TC 474
Z9 495
U1 12
U2 70
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD MAR 22
PY 2012
VL 119
IS 12
BP 2709
EP 2720
DI 10.1182/blood-2011-10-384388
PG 12
WC Hematology
SC Hematology
GA 916RU
UT WOS:000302121700007
PM 22160384
ER

PT J
AU Thomas, A
   Mailankody, S
   Korde, N
   Kristinsson, SY
   Turesson, I
   Landgren, O
AF Thomas, Anish
   Mailankody, Sham
   Korde, Neha
   Kristinsson, Sigurdur Y.
   Turesson, Ingemar
   Landgren, Ola
TI Second malignancies after multiple myeloma: from 1960s to 2010s
SO BLOOD
LA English
DT Review
ID ATOMIC-BOMB SURVIVORS; SEER CANCER REGISTRIES; PLASMA-CELL MYELOMA;
   UNDETERMINED SIGNIFICANCE; MYELODYSPLASTIC SYNDROME; MONOCLONAL
   GAMMOPATHY; HODGKINS-DISEASE; ACUTE-LEUKEMIA; UNITED-STATES;
   BREAST-CANCER
AB Based on small numbers, recent reports from 3 randomized trials have consistently demonstrated more hematologic malignancies in patients treated with lenalidomide as maintenance (vs placebo). This fact has prompted concern and highlighted the association between multiple myeloma and second malignancies. Furthermore, an excess of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) after multiple myeloma has been known for over 4 decades. Most prior studies have been restricted because of small numbers of patients, inadequate follow-up, and limitations of ascertainment of second malignancies. Although the underlying biologic mechanisms of AML/MDS after multiple myeloma are unknown, treatment-related factors are presumed to be responsible. Recently, an excess risk of AML/MDS was found among 5652 patients with IgG/IgA (but not IgM) monoclonal gammopathy of undetermined significance, supporting a role for disease-related factors. Furthermore, there is evidence to suggest that polymorphisms in germline genes may contribute to a person's susceptibility to subsequent cancers, whereas the potential influence of environmental and behavioral factors remains poorly understood. This review discusses current knowledge regarding second malignancies after multiple myeloma and gives future directions for efforts designed to characterize underlying biologic mechanisms, with the goal to maximize survival and minimize the risk for second malignancies for individual patients. (Blood. 2012; 119(12): 2731-2737)
C1 [Landgren, Ola] NCI, Multiple Myeloma Sect, Metab Branch, NIH, Bethesda, MD 20892 USA.
   [Kristinsson, Sigurdur Y.] Karolinska Univ Hosp & Inst, Dept Med, Stockholm, Sweden.
   [Turesson, Ingemar] Skane Univ Hosp, Div Med, Malmo, Sweden.
RP Landgren, O (reprint author), NCI, Multiple Myeloma Sect, Metab Branch, NIH, 9000 Rockville Pike,Bldg 10,Room 13N240, Bethesda, MD 20892 USA.
EM landgreo@mail.nih.gov
RI Kristinsson, Sigurdur /M-2910-2015; 
OI Kristinsson, Sigurdur /0000-0002-4964-7476; Thomas,
   Anish/0000-0003-3293-3115
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.
NR 71
TC 50
Z9 52
U1 2
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 MAR 22
PY 2012
VL 119
IS 12
BP 2731
EP 2737
DI 10.1182/blood-2011-12-381426
PG 7
WC Hematology
SC Hematology
GA 916RU
UT WOS:000302121700009
PM 22310913
ER

PT J
AU Simhadri, VR
   Andersen, JF
   Calvo, E
   Choi, SC
   Coligan, JE
   Borrego, F
AF Simhadri, Venkateswara R.
   Andersen, John F.
   Calvo, Eric
   Choi, Seung-Chul
   Coligan, John E.
   Borrego, Francisco
TI Human CD300a binds to phosphatidylethanolamine and phosphatidylserine,
   and modulates the phagocytosis of dead cells
SO BLOOD
LA English
DT Article
ID RECEPTOR IRP60 CD300A; IMMUNOGLOBULIN-LIKE RECEPTORS; INHIBITORY
   RECEPTOR; APOPTOTIC CELLS; ANNEXIN-V; GENERAL FEATURE; NK CELLS;
   B-CELLS; CLEARANCE; IDENTIFICATION
AB CD300a is an immunoreceptor tyrosine-based inhibitory motif (ITIM) containing molecule that belongs to the CD300 family of paired activating/inhibitory receptors. It has been shown that its ligation inhibits activation signals on cells of both myeloid and lymphoid lineages. The ligands for CD300a have not been identified. Here, we show that a CD300a-Ig fusion protein specifically binds to apoptotic cells that are evolutionary apart, such as human and insect cells, suggesting that the ligand has to be conserved. Using surface plasmon resonance, ultracentrifugation, ELISA, and reporter cell assays, we identified phosphatidylethanolamine (PE) and phosphatidylserine (PS), 2 phospholipids that translocate to the outer leaflet of the plasma membrane of dead cells, as the ligands for CD300a. Mutational and structural modeling studies identified residues that are involved in the binding of CD300a to PE and PS and that form a cavity where the hydrophilic heads of PE and PS, can penetrate. CD300a down-regulates the uptake of apoptotic cells by macrophages and its ectopic expression in CD300a-negative cell lines also decreased the engulfment of dead cells. Collectively, our results indicate that PE and PS are ligands for CD300a, and that this interaction plays an important role in regulating the removal of dead cells. (Blood. 2012; 119(12): 2799-2809)
C1 [Simhadri, Venkateswara R.; Borrego, Francisco] US FDA, Lab Mol & Dev Immunol, Div Monoclonal Antibodies, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA.
   [Andersen, John F.; Calvo, Eric] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
   [Choi, Seung-Chul; Coligan, John E.] NIAID, Receptor Cell Biol Sect, Immunogenet Lab, NIH, Bethesda, MD 20892 USA.
RP Borrego, F (reprint author), US FDA, Lab Mol & Dev Immunol, Div Monoclonal Antibodies, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bdg 29B,Rm 3NN18,29 Lincoln Dr,HFD-123, Bethesda, MD 20892 USA.
EM francisco.borrego@fda.hhs.gov
OI Calvo, Eric/0000-0001-7880-2730
FU Food and Drug Administration; National Institute of Allergy and
   Infectious Diseases
FX This work was funded by the intramural programs of the Food and Drug
   Administration and the National Institute of Allergy and Infectious
   Diseases.
NR 50
TC 55
Z9 56
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 MAR 22
PY 2012
VL 119
IS 12
BP 2799
EP 2809
DI 10.1182/blood-2011-08-372425
PG 11
WC Hematology
SC Hematology
GA 916RU
UT WOS:000302121700017
PM 22302738
ER

PT J
AU Kim, YC
   Bhairavabhotla, R
   Yoon, J
   Golding, A
   Thornton, AM
   Tran, DQ
   Shevach, EM
AF Kim, Yong Chan
   Bhairavabhotla, Ravikiran
   Yoon, Jeongheon
   Golding, Amit
   Thornton, Angela M.
   Tran, Dat Q.
   Shevach, Ethan M.
TI Oligodeoxynucleotides stabilize Helios-expressing Foxp3(+) human T
   regulatory cells during in vitro expansion
SO BLOOD
LA English
DT Article
ID VERSUS-HOST-DISEASE; TGF-BETA; VIVO
AB Foxp3(+) regulatory T cells (Tregs) maintain self-tolerance and adoptive therapy, and using Foxp3(+) Tregs has been proposed as treatment for autoimmune diseases. The clinical use of Tregs will require large numbers of cells and methods for in vitro expansion of Tregs are being developed. Foxp3(+) Tregs can be divided into 2 subpopulations based on expression of the transcription factor, Helios. Foxp3(+) Helios(+) Tregs (70%) are thymic-derived, whereas Foxp3(+) Helios(-) Tregs (30%) are induced in the periphery. Foxp3(+) Helios(+) Tregs differ from Foxp3(+) Helios(-) Tregs in terms of epigenetic changes at the Foxp3 locus, their capacity to produce effector cytokines, and their stability of Foxp3 expression on days to weeks of expansion in vitro. Addition of a 25 mer DNA oligonucleotide of random composition for a short period during the expansion of Foxp3(+) Tregs in vitro results in prolonged stabilization of the Foxp3(+)Helios(+) subpopulation and yields an optimal population for use in cellular biotherapy. (Blood. 2012; 119(12): 2810-2818)
C1 [Kim, Yong Chan; Bhairavabhotla, Ravikiran; Golding, Amit; Thornton, Angela M.; Shevach, Ethan M.] NIAID, Labs Immunol, NIH, Bethesda, MD 20892 USA.
   [Tran, Dat Q.] Univ Texas Med Sch, Dept Pediat, Houston, TX USA.
RP Shevach, EM (reprint author), NIAID, Immunol Lab, NIH, 10 Ctr Dr,Bldg 10,Rm 11N315, Bethesda, MD 20892 USA.
EM eshevach@niaid.nih.gov
OI Golding, Amit/0000-0003-3659-6654
FU Division of Intramural Research, National Institute of Allergy and
   Infectious Diseases (NIAID)
FX This study was supported by funds from the Division of Intramural
   Research, National Institute of Allergy and Infectious Diseases (NIAID).
NR 24
TC 54
Z9 54
U1 0
U2 5
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD MAR 22
PY 2012
VL 119
IS 12
BP 2810
EP 2818
DI 10.1182/blood-2011-09-377895
PG 9
WC Hematology
SC Hematology
GA 916RU
UT WOS:000302121700018
PM 22294730
ER

PT J
AU Recher, M
   Burns, SO
   de la Fuente, MA
   Volpi, S
   Dahlberg, C
   Walter, JE
   Moffitt, K
   Mathew, D
   Honke, N
   Lang, PA
   Patrizi, L
   Falet, H
   Keszei, M
   Mizui, M
   Csizmadia, E
   Candotti, F
   Nadeau, K
   Bouma, G
   Delmonte, OM
   Frugoni, F
   Fomin, ABF
   Buchbinder, D
   Lundequist, EM
   Massaad, MJ
   Tsokos, GC
   Hartwig, J
   Manis, J
   Terhorst, C
   Geha, RS
   Snapper, S
   Lang, KS
   Malley, R
   Westerberg, L
   Thrasher, AJ
   Notarangelo, LD
AF Recher, Mike
   Burns, Siobhan O.
   de la Fuente, Miguel A.
   Volpi, Stefano
   Dahlberg, Carin
   Walter, Jolan E.
   Moffitt, Kristin
   Mathew, Divij
   Honke, Nadine
   Lang, Philipp A.
   Patrizi, Laura
   Falet, Herve
   Keszei, Marton
   Mizui, Masayuki
   Csizmadia, Eva
   Candotti, Fabio
   Nadeau, Kari
   Bouma, Gerben
   Delmonte, Ottavia M.
   Frugoni, Francesco
   Fomin, Angela B. Ferraz
   Buchbinder, David
   Lundequist, Emma Maria
   Massaad, Michel J.
   Tsokos, George C.
   Hartwig, John
   Manis, John
   Terhorst, Cox
   Geha, Raif S.
   Snapper, Scott
   Lang, Karl S.
   Malley, Richard
   Westerberg, Lisa
   Thrasher, Adrian J.
   Notarangelo, Luigi D.
TI B cell-intrinsic deficiency of the Wiskott-Aldrich syndrome protein
   (WASp) causes severe abnormalities of the peripheral B-cell compartment
   in mice
SO BLOOD
LA English
DT Article
ID SPLENIC MARGINAL ZONE; REGULATORY T-CELLS; DENDRITIC CELLS; SYNAPSE
   FORMATION; IMMUNE-RESPONSE; IN-VITRO; AUTOIMMUNITY; HOMEOSTASIS;
   ACTIVATION; EXPANSION
AB Wiskott Aldrich syndrome (WAS) is caused by mutations in the WAS gene that encodes for a protein (WASp) involved in cytoskeleton organization in hematopoietic cells. Several distinctive abnormalities of T, B, and natural killer lymphocytes; dendritic cells; and phagocytes have been found in WASp-deficient patients and mice; however, the in vivo consequence of WASp deficiency within individual blood cell lineages has not been definitively evaluated. By conditional gene deletion we have generated mice with selective deficiency of WASp in the B-cell lineage (B/WcKO mice). We show that this is sufficient to cause a severe reduction of marginal zone B cells and inability to respond to type II T-independent Ags, thereby recapitulating phenotypic features of complete WASp deficiency. In addition, B/WcKO mice showed prominent signs of B-cell dysregulation, as indicated by an increase in serum IgM levels, expansion of germinal center B cells and plasma cells, and elevated autoantibody production. These findings are accompanied by hyperproliferation of WASp-deficient follicular and germinal center B cells in heterozygous B/WcKO mice in vivo and excessive differentiation of WASp-deficient B cells into class-switched plasmablasts in vitro, suggesting that WASp-dependent B cell-intrinsic mechanisms critically contribute to WAS-associated autoimmunity. (Blood. 2012;119(12):2819-2828)
C1 [Recher, Mike; de la Fuente, Miguel A.; Volpi, Stefano; Walter, Jolan E.; Mathew, Divij; Patrizi, Laura; Delmonte, Ottavia M.; Frugoni, Francesco; Fomin, Angela B. Ferraz; Lundequist, Emma Maria; Massaad, Michel J.; Geha, Raif S.; Notarangelo, Luigi D.] Childrens Hosp, Div Immunol, Boston, MA 02115 USA.
   [Recher, Mike; de la Fuente, Miguel A.; Volpi, Stefano; Walter, Jolan E.; Mathew, Divij; Patrizi, Laura; Delmonte, Ottavia M.; Frugoni, Francesco; Fomin, Angela B. Ferraz; Lundequist, Emma Maria; Massaad, Michel J.; Geha, Raif S.; Notarangelo, Luigi D.] Manton Ctr Orphan Dis Res, Boston, MA USA.
   [Burns, Siobhan O.; Bouma, Gerben; Thrasher, Adrian J.] Inst Child Hlth, Ctr Immunodeficiency, Mol Immunol Unit, London, England.
   [Burns, Siobhan O.; Thrasher, Adrian J.] Great Ormond St Hosp Children Natl Hlth Serv Trus, London, England.
   [de la Fuente, Miguel A.] Univ Valladolid, Inst Biol & Genet Mol, E-47002 Valladolid, Spain.
   [Dahlberg, Carin; Westerberg, Lisa] Karolinska Inst, Dept Med, Translat Immunol Unit, Stockholm, Sweden.
   [Moffitt, Kristin; Malley, Richard] Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA.
   [Honke, Nadine; Lang, Philipp A.; Lang, Karl S.] Univ Dusseldorf, Dept Gastroenterol Hepatol & Infectiol, D-40225 Dusseldorf, Germany.
   [Falet, Herve; Hartwig, John] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Translat Med,Brigham & Womens Hosp, Boston, MA 02115 USA.
   [Keszei, Marton; Terhorst, Cox] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Immunol, Boston, MA 02215 USA.
   [Mizui, Masayuki; Tsokos, George C.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Rheumatol, Boston, MA 02215 USA.
   [Csizmadia, Eva] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Transplantat Inst,Dept Med, Boston, MA 02215 USA.
   [Candotti, Fabio] NHGRI, Disorders Immun Sect, Genet & Mol Biol Branch, Bethesda, MD 20892 USA.
   [Nadeau, Kari] Stanford Med Sch, Div Immunol & Allergy, Stanford, CA USA.
   [Nadeau, Kari] Lucile Packard Childrens Hosp, Stanford, CA USA.
   [Buchbinder, David] Univ Calif Irvine, Childrens Hosp Orange Cty, Div Pediat Hematol, Orange, CA USA.
   [Manis, John] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   [Snapper, Scott] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Gastroenterol, Boston, MA USA.
   [Lang, Karl S.] Univ Essen Gesamthsch, Inst Immunol, Essen, Germany.
RP Thrasher, AJ (reprint author), UCL Inst Child Hlth, Ctr Immunodeficiency, Mol Immunol Unit, 30 Guilford St, London WC1N 1EH, England.
EM a.thrasher@ich.ucl.ac.uk; luigi.notarangelo@childrens.harvard.edu
RI de la Fuente, Miiguel /C-7478-2013; Dahlberg, Carin/N-1625-2013; Keszei,
   Marton/F-3295-2014; Volpi, Stefano/O-3717-2014; Notarangelo,
   Luigi/F-9718-2016; Lang, Karl/R-2505-2016; 
OI Falet, Herve/0000-0003-0788-9204; de la Fuente, Miiguel
   /0000-0003-4619-8756; Dahlberg, Carin/0000-0002-8610-6302; Keszei,
   Marton/0000-0002-1158-2179; Volpi, Stefano/0000-0002-7129-868X;
   Notarangelo, Luigi/0000-0002-8335-0262; Bouma,
   Gerben/0000-0002-1465-9178; Westerberg, Lisa/0000-0003-2943-2192;
   Frugoni, Francesco/0000-0002-1769-8121
FU National Institutes of Health [2PO1HL059561-11-A1]; Manton Foundation;
   Swiss National Science Foundation (SNSF/SSMBS) [PASMP3-127678];
   Karolinska Institutet; Swedish Research Foundation; FIS-ISCIII [PI10/02
   511]; Consejeria de Educacion [VA244A11-2]; Wellcome Trust; Primary
   Immunodeficiency Association through the Academy of Medical Sciences
FX This work was supported by the National Institutes of Health (grant
   2PO1HL059561-11-A1, L.D.N.) and the Manton Foundation (L.D.N.); the
   Swiss National Science Foundation (SNSF/SSMBS; grant PASMP3-127678, M.
   R.); the Karolinska Institutet (L. W.); the Swedish Research Foundation
   (L. W.); FIS-ISCIII (grant PI10/02 511, M.A.d.l.F.); Consejeria de
   Educacion (M.A.d.l.F.; grant VA244A11-2, J.d.C.y.L.); the Wellcome Trust
   (A.J.T. and G. B.); and by a grant from the Primary Immunodeficiency
   Association through the Academy of Medical Sciences (S.O.B.).
NR 48
TC 42
Z9 44
U1 1
U2 4
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD MAR 22
PY 2012
VL 119
IS 12
BP 2819
EP 2828
DI 10.1182/blood-2011-09-379412
PG 10
WC Hematology
SC Hematology
GA 916RU
UT WOS:000302121700019
PM 22302739
ER

PT J
AU Enose-Akahata, Y
   Abrams, A
   Johnson, KR
   Maloney, EM
   Jacobson, S
AF Enose-Akahata, Yoshimi
   Abrams, Anna
   Johnson, Kory R.
   Maloney, Elizabeth M.
   Jacobson, Steven
TI Quantitative differences in HTLV-I antibody responses: classification
   and relative risk assessment for asymptomatic carriers and ATL and
   HAM/TSP patients from Jamaica
SO BLOOD
LA English
DT Article
ID VIRUS TYPE-I; T-CELL LEUKEMIA; MYELOPATHY/TROPICAL SPASTIC PARAPARESIS;
   PROVIRAL DNA LOAD; PERIPHERAL-BLOOD; NATURAL-HISTORY; LEUKEMIA/LYMPHOMA;
   DISEASE; LYMPHOCYTES; INFECTION
AB Adult T-cell leukemia (ATL) and human T-cell lymphotropic virus type I (HTLV-I)associated myelopathy/tropical spastic paraparesis (HAM/TSP) are known to be caused by HTLV-I infection. However, current methods used to determine HTLV-I infection do not differentiate between HTLV-I asymptomatic carriers (ACs) and ATL and HAM/TSP patients. Using the luciferase immunoprecipitation system, a highly sensitive, quantitative technology that can efficiently detect HTLV-I Ab responses, we examined Ab responses for HTLV-I in serum/plasma samples from 439 subjects in Jamaica, including HTLVI- seronegative donors, ACs, and ATL and HAM/TSP patients. The Ab responses of HTLV-I-infected subjects differed significantly from those of seronegative donors for all 3 immunodominant proteins, Gag, Env, and Tax. HAM/TSP patients had significantly higher Ab responses for Gag and Env compared with ACs, and Ab responses for all 3 Ags were higher in HAM/TSP patients than in ATL patients. Moreover, immunoreactivities for HTLV-I Ags as determined by the luciferase immunoprecipitation system could distinguish HAM/TSP patients from ACs at a true-positive rate of 85.42% and from ATL patients at a true-positive rate of 75.00%, and modeled in conjunction with subject information to distinguish HAM/TSP patients from ACs (odds ratio=14.12) and from ATL patients (odds ratio=7.00). The relative risk assessment resulting from these significant differences between Ab responses in HTLVI-infected groups may be a useful diagnostic tool in the future. (Blood. 2012; 119(12): 2829-2836)
C1 [Enose-Akahata, Yoshimi; Abrams, Anna; Jacobson, Steven] NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
   [Johnson, Kory R.] NINDS, Informat Technol & Bioinformat Program, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
   [Maloney, Elizabeth M.] US FDA, Div Epidemiol 2, Off Surveillance & Epidemiol, Silver Spring, MD USA.
RP Jacobson, S (reprint author), NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
EM jacobsons@ninds.nih.gov
FU National Institute of Neurological Disorders and Stroke, NIH
FX This research was supported by the Intramural Research Program of the
   National Institute of Neurological Disorders and Stroke, NIH.
NR 46
TC 11
Z9 11
U1 0
U2 0
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD MAR 22
PY 2012
VL 119
IS 12
BP 2829
EP 2836
DI 10.1182/blood-2011-11-390807
PG 8
WC Hematology
SC Hematology
GA 916RU
UT WOS:000302121700020
PM 22318200
ER

PT J
AU Greenblatt, S
   Li, L
   Slape, C
   Nguyen, B
   Novak, R
   Duffield, A
   Huso, D
   Desiderio, S
   Borowitz, MJ
   Aplan, P
   Small, D
AF Greenblatt, Sarah
   Li, Li
   Slape, Christopher
   Bao Nguyen
   Novak, Rachel
   Duffield, Amy
   Huso, David
   Desiderio, Stephen
   Borowitz, Michael J.
   Aplan, Peter
   Small, Donald
TI Knock-in of a FLT3/ITD mutation cooperates with a NUP98-HOXD13 fusion to
   generate acute myeloid leukemia in a mouse model
SO BLOOD
LA English
DT Article
ID INTERNAL TANDEM DUPLICATION; ACUTE MYELOGENOUS LEUKEMIA; WILD-TYPE
   ALLELE; HEMATOPOIETIC STEM-CELLS; BONE-MARROW; MYELODYSPLASTIC SYNDROME;
   EXPRESSION PATTERN; RECEPTOR GENE; HOX GENES; EX-VIVO
AB Constitutive activation of FLT3 by internal tandem duplication (ITD) is one of the most common molecular alterations in acute myeloid leukemia (AML). FLT3/ITD mutations have also been observed in myelodysplastic syndrome patients both before and during progression to AML. Previous work has shown that insertion of an FLT3/ITD mutation into the murine Flt3 gene induces a myeloproliferative neoplasm, but not progression to acute leukemia, suggesting that additional cooperating events are required. We therefore combined the FLT3/ITD mutation with a model of myelodysplastic syndrome involving transgenic expression of the Nup98-HoxD13 (NHD13) fusion gene. Mice expressing both the FLT3/ITD and NHD13 transgene developed AML with 100% penetrance and short latency. These leukemias were driven by mutant FLT3 expression and were susceptible to treatment with FLT3 tyrosine kinase inhibitors. We also observed a spontaneous loss of the wild-type Flt3 allele in these AMLs, further modeling the loss of the heterozygosity phenomenon that is seen in human AML with FLT3-activating mutations. Because resistance to FLT3 inhibitors remains an important clinical issue, this model may help identify new molecular targets in collaborative signaling pathways. (Blood. 2012;119(12):2883-2894)
C1 [Greenblatt, Sarah; Li, Li; Bao Nguyen; Small, Donald] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA.
   [Slape, Christopher] Monash Univ, Cent Clin Sch, Melbourne, Vic 3004, Australia.
   [Novak, Rachel; Aplan, Peter] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
   [Duffield, Amy; Borowitz, Michael J.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
   [Huso, David] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD 21205 USA.
   [Desiderio, Stephen] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA.
   [Small, Donald] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA.
RP Small, D (reprint author), Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, CRB Rm 251,1650 Orleans St, Baltimore, MD 21231 USA.
EM donsmall@jhmi.edu
RI Aplan, Peter/K-9064-2016; Slape, Christopher/H-8586-2016
OI Slape, Christopher/0000-0002-8407-3092
FU National Cancer Institute [CA90668, CA70970]; Leukemia & Lymphoma
   Society; Giant Food Pediatric Cancer Research Fund; National Institutes
   of Health, National Cancer Institute; Kyle Haydock Professorship
FX This work was supported by the National Cancer Institute (CA90668,
   CA70970), Leukemia & Lymphoma Society, the Giant Food Pediatric Cancer
   Research Fund, and the Intramural Research Program of the National
   Institutes of Health, National Cancer Institute. D. S. is also supported
   by the Kyle Haydock Professorship.
NR 47
TC 28
Z9 29
U1 0
U2 4
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD MAR 22
PY 2012
VL 119
IS 12
BP 2883
EP 2894
DI 10.1182/blood-2011-10-382283
PG 12
WC Hematology
SC Hematology
GA 916RU
UT WOS:000302121700026
PM 22323452
ER

PT J
AU Zhang, Y
   Morgan, MJ
   Chen, K
   Choksi, S
   Liu, ZG
AF Zhang, Yan
   Morgan, Michael J.
   Chen, Kun
   Choksi, Swati
   Liu, Zheng-gang
TI Induction of autophagy is essential for monocyte-macrophage
   differentiation
SO BLOOD
LA English
DT Article
ID VITAMIN-D3 INDUCES AUTOPHAGY; MEDIATED CLEAVAGE; HUMAN
   MONOCYTES/MACROPHAGES; SELF-DIGESTION; T-LYMPHOCYTES; CELL-DEATH;
   C-ELEGANS; LIFE-SPAN; BECLIN 1; APOPTOSIS
AB Monocytes are programmed to undergo apoptosis in the absence of stimulation. Stimuli that promote monocyte-macrophage differentiation not only cause cellular changes, but also prevent the default apoptosis of monocytes. In the present study, we demonstrate that autophagy is induced when monocytes are triggered to differentiate and that the induction of autophagy is pivotal for the survival and differentiation of monocytes. We also show that inhibition of autophagy results in apoptosis of cells that are engaged in differentiation. We found that the differentiation signal releases Beclin1 from Bcl-2 by activating JNK and blocks Atg5 cleavage, both of which are critical for the induction of autophagy. Preventing autophagy induction hampers differentiation and cytokine production; therefore, autophagy is an important transition from monocyte apoptosis to differentiation. (Blood. 2012;119(12):2895-2905)
C1 [Zhang, Yan; Choksi, Swati; Liu, Zheng-gang] NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Morgan, Michael J.] Univ Colorado, Sch Med, Dept Pharmacol, Aurora, CO USA.
   [Chen, Kun] Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Jiangsu Diabet Res Ctr, Sch Life Sci, Nanjing 210008, Peoples R China.
RP Liu, ZG (reprint author), NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bldg 37,Rm 1130,37 Convent Dr, Bethesda, MD 20892 USA.
EM zgliu@helix.nih.gov
FU Center for Cancer Research (NCI)
FX This study was supported by the Intramural Research Program of The
   Center for Cancer Research (NCI).
NR 50
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Z9 66
U1 0
U2 10
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD MAR 22
PY 2012
VL 119
IS 12
BP 2895
EP 2905
DI 10.1182/blood-2011-08-372383
PG 11
WC Hematology
SC Hematology
GA 916RU
UT WOS:000302121700027
PM 22223827
ER

PT J
AU Hardy, NM
   Fellowes, V
   Rose, JJ
   Odom, J
   Pittaluga, S
   Steinberg, SM
   Blacklock-Schuver, B
   Avila, DN
   Memon, S
   Kurlander, RJ
   Khuu, HM
   Stetler-Stevenson, M
   Mena, E
   Dwyer, AJ
   Levine, BL
   June, CH
   Reshef, R
   Vonderheide, RH
   Gress, RE
   Fowler, DH
   Hakim, FT
   Bishop, MR
AF Hardy, Nancy M.
   Fellowes, Vicki
   Rose, Jeremy J.
   Odom, Jeanne
   Pittaluga, Stefania
   Steinberg, Seth M.
   Blacklock-Schuver, Bazetta
   Avila, Daniele N.
   Memon, Sarfraz
   Kurlander, Roger J.
   Khuu, Hahn M.
   Stetler-Stevenson, Maryalice
   Mena, Esther
   Dwyer, Andrew J.
   Levine, Bruce L.
   June, Carl H.
   Reshef, Ran
   Vonderheide, Robert H.
   Gress, Ronald E.
   Fowler, Daniel H.
   Hakim, Frances T.
   Bishop, Michael R.
TI Costimulated tumor-infiltrating lymphocytes are a feasible and safe
   alternative donor cell therapy for relapse after allogeneic stem cell
   transplantation
SO BLOOD
LA English
DT Article
ID I CLINICAL-TRIAL; T-CELLS; LEUKOCYTE INFUSIONS; PERSISTENCE; MALIGNANCY;
   REGRESSION; VIVO
AB Donor lymphocyte infusion (DLI), a standard relapse treatment after allogeneic stem cell transplantation (AlloSCT), has limited efficacy and often triggers GVHD. We hypothesized that after AlloSCT tumor-infiltrating donor lymphocytes could be costimulated ex vivo to preferentially activate/expand antitumor effectors. We tested the feasibility and safety of costimulated, tumor-derived donor lymphocyte (TDL) infusion in a phase 1 trial. Tumor was resected from 8 patients with B-cell malignancy progression post-AlloSCT; tumor cell suspensions were costimulated with anti-CD3/anti-CD28 Ab-coated magnetic beads and cultured to generate TDL products for each patient. Costimulation yielded increased proportions of T-bet(+)FoxP3(-) type 1 effector donor T cells. A median of 2.04 x 10(7) TDL/kg was infused; TDLs were well tolerated, notably without GVHD. Two transient positron emission tomography (PET) responses and 2 mixed responses were observed in these refractory tumors. TDL are a feasible, tolerable, and novel donor cell therapy alternative for relapse after AlloSCT. This trial is registered at clinicaltrials.gov as no. NCT00445666. (Blood. 2012;119(12):2956-2959)
C1 [Hardy, Nancy M.] NCI, Expt Transplantat & Immunol Branch, CCR, Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
   [Pittaluga, Stefania; Stetler-Stevenson, Maryalice] NCI, CCR, Pathol Lab, Bethesda, MD 20892 USA.
   [Steinberg, Seth M.] NCI, CCR, Biostat & Data Management Sect, Bethesda, MD 20892 USA.
   [Kurlander, Roger J.] NCI, CCR, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
   [Khuu, Hahn M.] NCI, CCR, Dept Transfus Med, CC, Bethesda, MD 20892 USA.
   [Mena, Esther] NCI, CCR, Mol Imaging Program, Bethesda, MD 20892 USA.
   [Dwyer, Andrew J.] NIH, Dept Radiol & Imagine Sci, CC, Bethesda, MD 20892 USA.
   [Levine, Bruce L.; June, Carl H.; Reshef, Ran; Vonderheide, Robert H.] Univ Penn, Dept Pathol & Lab Med, Abramson Canc Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Bishop, Michael R.] Med Coll Wisconsin, Div Hematol & Oncol, Ctr Clin Canc, Milwaukee, WI 53226 USA.
RP Hardy, NM (reprint author), NCI, Expt Transplantat & Immunol Branch, CCR, Hatfield Clin Res Ctr, 10 Ctr Dr,Room 3E-3330, Bethesda, MD 20892 USA.
EM hardyn@mail.nih.gov
RI Levine, Bruce/D-1688-2009
FU Intramural National Cancer Institute, Center for Cancer Research
   (Bethesda, MD)
FX This work was supported by the Intramural National Cancer Institute,
   Center for Cancer Research (Bethesda, MD).
NR 18
TC 13
Z9 13
U1 0
U2 4
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAR 22
PY 2012
VL 119
IS 12
BP 2956
EP 2959
DI 10.1182/blood-2011-09-378398
PG 4
WC Hematology
SC Hematology
GA 916RU
UT WOS:000302121700034
PM 22289893
ER

PT J
AU Molnar, Z
   Belgard, TG
AF Molnar, Zoltan
   Belgard, T. Grant
TI Transcriptional Profiling of Layers of the Primate Cerebral Cortex
SO NEURON
LA English
DT Editorial Material
ID HUMAN BRAIN; AREAS; RNA
AB In this issue of Neuron, Bernard et al. (2012) report microarray-based transcriptional profiling of individually isolated layers from several cortical areas in adult Rhesus monkeys (Macaca mulatta). The resulting molecular signatures of neocortical organization are compared with human and mouse.
C1 [Molnar, Zoltan; Belgard, T. Grant] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3QX, England.
   [Belgard, T. Grant] Univ Oxford, MRC Funct Genom Unit, Oxford OX1 3QX, England.
   [Belgard, T. Grant] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
RP Belgard, TG (reprint author), Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3QX, England.
EM zoltan.molnar@dpag.ox.ac.uk; grant@grantbelgard.com
OI Molnar, Zoltan/0000-0002-6852-6004; Belgard, Tildon/0000-0002-6962-7894
FU Medical Research Council [G0900901]
NR 15
TC 5
Z9 5
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD MAR 22
PY 2012
VL 73
IS 6
BP 1053
EP 1055
DI 10.1016/j.neuron.2012.03.007
PG 3
WC Neurosciences
SC Neurosciences & Neurology
GA 915BU
UT WOS:000301998700001
PM 22445331
ER

PT J
AU Johansen-Berg, H
   Baptista, CS
   Thomas, AG
AF Johansen-Berg, Heidi
   Baptista, Cassandra Sampaio
   Thomas, Adam G.
TI Human Structural Plasticity at Record Speed
SO NEURON
LA English
DT Editorial Material
AB How rapidly does learning shape our brains? A new study in this issue of Neuron by Sagi et al. (2012) that uses diffusion magnetic resonance imaging in both humans and rats suggests that just 2 hr of spatial learning is sufficient to change brain structure.
C1 [Johansen-Berg, Heidi; Baptista, Cassandra Sampaio; Thomas, Adam G.] John Radcliffe Hosp, Oxford Ctr Funct MRI Brain, Nuffield Dept Clin Neurosci, Oxford OX3 9DU, England.
   [Thomas, Adam G.] NIMH, Funct MRI Facil, NIH, Bethesda, MD 20892 USA.
RP Johansen-Berg, H (reprint author), John Radcliffe Hosp, Oxford Ctr Funct MRI Brain, Nuffield Dept Clin Neurosci, Oxford OX3 9DU, England.
EM heidi@fmrib.ox.ac.uk
OI , /0000-0002-7893-0289; Johansen-Berg, Heidi/0000-0002-4134-9730;
   Thomas, Adam/0000-0002-2850-1419
FU Intramural NIH HHS [Z99 MH999999]; Medical Research Council [G0700399];
   Wellcome Trust [090955]
NR 12
TC 25
Z9 25
U1 0
U2 12
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD MAR 22
PY 2012
VL 73
IS 6
BP 1058
EP 1060
DI 10.1016/j.neuron.2012.03.001
PG 3
WC Neurosciences
SC Neurosciences & Neurology
GA 915BU
UT WOS:000301998700003
PM 22445333
ER

PT J
AU Sharma, S
   Bhaumik, P
   Schmitz, W
   Venkatesan, R
   Hiltunen, JK
   Conzelmann, E
   Juffer, AH
   Wierenga, RK
AF Sharma, Satyan
   Bhaumik, Prasenjit
   Schmitz, Werner
   Venkatesan, Rajaram
   Hiltunen, J. Kalervo
   Conzelmann, Ernst
   Juffer, Andre H.
   Wierenga, Rik K.
TI The Enolization Chemistry of a Thioester-Dependent Racemase: The 1.4
   angstrom Crystal Structure of a Reaction Intermediate Complex
   Characterized by Detailed QM/MM Calculations
SO JOURNAL OF PHYSICAL CHEMISTRY B
LA English
DT Article
ID METHYLACYL-COA RACEMASE; SERINE-PROTEASE CATALYSIS; BILE-ACID SYNTHESIS;
   MANDELATE RACEMASE; TRANSITION-STATE; MOLECULAR-DYNAMICS; CITRATE
   SYNTHASE; ENZYME CATALYSIS; ACTIVE-SITE; MYCOBACTERIUM-TUBERCULOSIS
AB In the active site of the bacterial alpha-methylacyl-CoA racemase of Mycobacterium tuberculosis (MCR), the chirality of the 2-methyl branched C2-atom is interconverted between (S) and (R) isomers. Protein crystallographic data and quantum mechanics/molecular mechanics (QM/MM) computational approaches show that this interconversion is achieved via a planar enolate intermediate. The crystal structure, at 1.4 angstrom, visualizes the mode of binding of a reaction intermediate analogue, 2-methylacetoacetyl-CoA, in a well-defined planar enolate form. The computational studies confirm that in the conversion from (S) to (R), first a proton is abstracted by N delta 1 (His126), and subsequently the planar enolate form is reprotonated by O delta 2 (Asp156). The calculations also show that the negatively charged thioester oxygen of the enolate intermediate is stabilized by an oxyanion hole formed by N (Asp127), as well as by the side chain atoms of the catalytic residues, Asp 156 and His 126, both being protonated simultaneously, at the intermediate stage of the catalytic cycle. The computational analysis also reveals that the conversion of the (S)- to (R)- chirality is achieved by a movement of 1.7 angstrom of the chiral C2-carbon, with smaller shifts (approximately 1 angstrom) of the carbon atom of the 2-methyl group, the C3-atom of the fatty acid tail, and the C1-carbon and O1-oxygen atoms of the thioester moiety.
C1 [Sharma, Satyan; Venkatesan, Rajaram; Hiltunen, J. Kalervo; Juffer, Andre H.; Wierenga, Rik K.] Univ Oulu, Bioctr Oulu, FI-90014 Oulu, Finland.
   [Sharma, Satyan; Venkatesan, Rajaram; Hiltunen, J. Kalervo; Juffer, Andre H.; Wierenga, Rik K.] Univ Oulu, Dept Biochem, FI-90014 Oulu, Finland.
   [Bhaumik, Prasenjit] NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA.
   [Schmitz, Werner; Conzelmann, Ernst] Univ Wurzburg, Theodor Boveri Inst Biowissensch, Biozentrum, D-97074 Wurzburg, Germany.
RP Wierenga, RK (reprint author), Univ Oulu, Bioctr Oulu, POB 3000, FI-90014 Oulu, Finland.
EM rik.wierenga@oulu.fi
FU Academy of Finland; Sigrid Juselius Foundation
FX We thank Paivi Pirilla for providing us with the
   2-methylacetoacetyl-CoA. We thank the beamline scientists of ID 14-2 for
   excellent support. We thank CSC (Center of Scientific Computing) in
   Espoo (Finland) for providing computing power. This work was supported
   by grants from the Academy of Finland and the Sigrid Juselius
   Foundation.
NR 76
TC 9
Z9 9
U1 2
U2 18
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1520-6106
J9 J PHYS CHEM B
JI J. Phys. Chem. B
PD MAR 22
PY 2012
VL 116
IS 11
BP 3619
EP 3629
DI 10.1021/jp210185m
PG 11
WC Chemistry, Physical
SC Chemistry
GA 912AV
UT WOS:000301766700015
PM 22360758
ER

PT J
AU Narendra, DP
   Youle, RJ
AF Narendra, Derek P.
   Youle, Richard J.
TI NEURODEGENERATION Trouble in the cell's powerhouse
SO NATURE
LA English
DT Editorial Material
ID RECESSIVE SPASTIC ATAXIA; DYNAMIN-RELATED PROTEIN; DOMINANT OPTIC
   ATROPHY; CHARLEVOIX-SAGUENAY; MITOCHONDRIA; MUTATIONS; FISSION; ARSACS;
   OPA1
C1 [Narendra, Derek P.; Youle, Richard J.] Natl Inst Neurol Disorders & Stroke, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
RP Narendra, DP (reprint author), Natl Inst Neurol Disorders & Stroke, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
EM youler@ninds.nih.gov
FU Intramural NIH HHS [Z99 NS999999]
NR 14
TC 10
Z9 10
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD MAR 22
PY 2012
VL 483
IS 7390
BP 418
EP 419
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 912CC
UT WOS:000301771200033
PM 22398449
ER

PT J
AU Tsang, PS
   Cheuk, AT
   Chen, QR
   Song, YK
   Badgett, TC
   Wei, JS
   Khan, J
AF Tsang, Patricia S.
   Cheuk, Adam T.
   Chen, Qing-Rong
   Song, Young K.
   Badgett, Thomas C.
   Wei, Jun S.
   Khan, Javed
TI Synthetic Lethal Screen Identifies NF-kappa B as a Target for
   Combination Therapy with Topotecan for patients with Neuroblastoma
SO BMC CANCER
LA English
DT Article
ID CHILDRENS ONCOLOGY GROUP; GROUP PHASE-II; BONE-MARROW-TRANSPLANTATION;
   PROTEASOME INHIBITOR PS-341; HIGH-RISK NEUROBLASTOMA; CELL LUNG-CANCER;
   SOLID TUMORS; REFRACTORY NEUROBLASTOMA; TOPOISOMERASE-I; BORTEZOMIB
AB Background: Despite aggressive multimodal treatments the overall survival of patients with high-risk neuroblastoma remains poor. The aim of this study was to identify novel combination chemotherapy to improve survival rate in patients with high-risk neuroblastoma.
   Methods: We took a synthetic lethal approach using a siRNA library targeting 418 apoptosis-related genes and identified genes and pathways whose inhibition synergized with topotecan. Microarray analyses of cells treated with topotecan were performed to identify if the same genes or pathways were altered by the drug. An inhibitor of this pathway was used in combination with topotecan to confirm synergism by in vitro and in vivo studies.
   Results: We found that there were nine genes whose suppression synergized with topotecan to enhance cell death, and the NF-kappa B signaling pathway was significantly enriched. Microarray analysis of cells treated with topotecan revealed a significant enrichment of NF-kappa B target genes among the differentially altered genes, suggesting that NF-kappa B pathway was activated in the treated cells. Combination of topotecan and known NF-kappa B inhibitors (NSC 676914 or bortezomib) significantly reduced cell growth and induced caspase 3 activity in vitro. Furthermore, in a neuroblastoma xenograft mouse model, combined treatment of topotecan and bortezomib significantly delayed tumor formation compared to single-drug treatments.
   Conclusions: Synthetic lethal screening provides a rational approach for selecting drugs for use in combination therapy and warrants clinical evaluation of the efficacy of the combination of topotecan and bortezomib or other NF-kappa B inhibitors in patients with high risk neuroblastoma.
C1 [Tsang, Patricia S.; Cheuk, Adam T.; Chen, Qing-Rong; Song, Young K.; Badgett, Thomas C.; Wei, Jun S.; Khan, Javed] NCI, Oncogen Sect, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Khan, J (reprint author), NCI, Oncogen Sect, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
EM khanjav@mail.nih.gov
RI Khan, Javed/P-9157-2014
OI Khan, Javed/0000-0002-5858-0488
FU National Institutes of Health, National Cancer Institute, Center for
   Cancer Research
FX We would like to thank Dr Paul Meltzer, Dr Natasha Caplen and Dr Scott
   Martin for providing the siRNA library and for useful discussions; and
   Dr David Azorsa for helpful technical advice. This work was supported by
   the Intramural Research Program of the National Institutes of Health,
   National Cancer Institute, Center for Cancer Research. The content of
   this publication does not necessarily reflect the views or policies of
   the Department of Health and Human Services, nor does mention of trade
   names, commercial products, or organizations imply endorsement by the
   U.S. government.
NR 40
TC 6
Z9 7
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2407
J9 BMC CANCER
JI BMC Cancer
PD MAR 21
PY 2012
VL 12
AR 101
DI 10.1186/1471-2407-12-101
PG 10
WC Oncology
SC Oncology
GA 951FC
UT WOS:000304705200001
PM 22436457
ER

PT J
AU Ma, JL
   Zhang, L
   Brown, LM
   Li, JY
   Shen, L
   Pan, KF
   Liu, WD
   Hu, YR
   Han, ZX
   Crystal-Mansour, S
   Pee, D
   Blot, WJ
   Fraumeni, JF
   You, WC
   Gail, MH
AF Ma, Jun-Ling
   Zhang, Lian
   Brown, Linda M.
   Li, Ji-You
   Shen, Lin
   Pan, Kai-Feng
   Liu, Wei-Dong
   Hu, Yuanreng
   Han, Zhong-Xiang
   Crystal-Mansour, Susan
   Pee, David
   Blot, William J.
   Fraumeni, Joseph F., Jr.
   You, Wei-Cheng
   Gail, Mitchell H.
TI Fifteen-Year Effects of Helicobacter pylori, Garlic, and Vitamin
   Treatments on Gastric Cancer Incidence and Mortality
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID GENERAL-POPULATION; FACTORIAL TRIAL; SUPPLEMENTATION; LINXIAN; LESIONS;
   REDUCE; CHINA; RISK
AB In the Shandong Intervention Trial, 2 weeks of antibiotic treatment for Helicobacter pylori reduced the prevalence of precancerous gastric lesions, whereas 7.3 years of oral supplementation with garlic extract and oil (garlic treatment) or vitamin C, vitamin E, and selenium (vitamin treatment) did not. Here we report 14.7-year follow-up for gastric cancer incidence and cause-specific mortality among 3365 randomly assigned subjects in this masked factorial placebo-controlled trial. Conditional logistic regression was used to estimate the odds of gastric cancer incidence, and the Cox proportional hazards model was used to estimate the relative hazard of cause-specific mortality. All statistical tests were two-sided. Gastric cancer was diagnosed in 3.0% of subjects who received H pylori treatment and in 4.6% of those who received placebo (odds ratio = 0.61, 95% confidence interval = 0.38 to 0.96, P = .032). Gastric cancer deaths occurred among 1.5% of subjects assigned H pylon treatment and among 2.1% of those assigned placebo (hazard ratio [HR] of death = 0.67, 95% CI = 0.36 to 1.28). Garlic and vitamin treatments were associated with non-statistically significant reductions in gastric cancer incidence and mortality. Vitamin treatment was associated with statistically significantly fewer deaths from gastric or esophageal cancer, a secondary endpoint (HR = 0.51, 95% CI = 0.30 to 0.87; P = .014).
C1 [Fraumeni, Joseph F., Jr.; Gail, Mitchell H.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Ma, Jun-Ling; Zhang, Lian; Li, Ji-You; Shen, Lin; Pan, Kai-Feng; You, Wei-Cheng] Peking Univ, Key Lab Carcinogenesis & Translat Res, Minist Educ, Sch Oncol,Beijing Canc Hosp, Beijing 100142, Peoples R China.
   [Ma, Jun-Ling; Zhang, Lian; Li, Ji-You; Shen, Lin; Pan, Kai-Feng; You, Wei-Cheng] Beijing Inst Canc Res, Beijing, Peoples R China.
   [Hu, Yuanreng; Crystal-Mansour, Susan] Westat Corp, Rockville, MD USA.
   [Pee, David] Informat Management Serv Inc, Rockville, MD USA.
   [Brown, Linda M.] RTI Int, Rockville, MD USA.
   [Blot, William J.] Int Epidemiol Inst Ltd, Rockville, MD USA.
   [Blot, William J.] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
RP Gail, MH (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8032, Bethesda, MD 20892 USA.
EM weichengyou@yahoo.com; gailm@mail.nih.gov
FU National Institutes of Health, National Cancer Institute; National
   Cancer Institute [NO2-CP-71103, NO2-CP-21169]; National Basic Research
   Program of China [2004CB518702, 2010CB529303]
FX This research was supported by the Intramural Research Program of the
   National Institutes of Health, National Cancer Institute, and in part by
   National Cancer Institute Contracts NO2-CP-71103 and NO2-CP-21169.
   National Cancer Institute contracts also supported work at Westat and at
   Information Management Services. Additional support was from the
   National Basic Research Program of China (973 program: 2004CB518702 and
   2010CB529303).
NR 10
TC 130
Z9 149
U1 2
U2 42
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD MAR 21
PY 2012
VL 104
IS 6
BP 488
EP 492
DI 10.1093/jnci/djs003
PG 5
WC Oncology
SC Oncology
GA 913PF
UT WOS:000301889200012
PM 22271764
ER

PT J
AU Derbyshire, MK
   Lanczycki, CJ
   Bryant, SH
   Marchler-Bauer, A
AF Derbyshire, Myra K.
   Lanczycki, Christopher J.
   Bryant, Stephen H.
   Marchler-Bauer, Aron
TI Annotation of functional sites with the Conserved Domain Database
SO DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION
LA English
DT Article
ID PROTEIN; SEQUENCES; CDD
AB The overwhelming fraction of proteins whose sequences have been collected in comprehensive databases may never be assessed for function experimentally. Commonly, putative function is assigned based on similarity to experimentally characterized homologs, either on the level of the entire protein or for single evolutionarily conserved domains. The annotation of individual sites provides more detailed insights regarding the correspondence between sequence and function, as well as context for the interpretation of sequence variation and the outcomes of experiments. In general, site annotation has to be extracted from the published literature, and can often be transferred to closely related sequence neighbors. The National Center for Biotechnology Information's Conserved Domain Database (CDD) provides a system for curators to record functional (such as active sites or binding sites for cofactors) or characteristic sites (such as signature motifs), which are conserved across domain families, and for the transfer of that annotation to protein database sequences via high-confidence domain matches. Recently, CDD curators have begun to sort-site annotations into seven categories (active, polypeptide binding, nucleic acid binding, ion binding, chemical binding, post-translational modification and other) and here we present a first comparative analysis of sites obtained via domain model matches, juxtaposed with existing site annotation encountered in high-quality data sets. Site annotation derived from domain annotation has the potential to cover large fractions of protein sequences, and we observe that CDD-based site annotation complements existing site annotation in many cases, which may, in part, originate from CDD's curation practice of collecting sites conserved across diverse taxa and supported by evidence from multiple 3D structures.
C1 [Derbyshire, Myra K.; Lanczycki, Christopher J.; Bryant, Stephen H.; Marchler-Bauer, Aron] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Marchler-Bauer, A (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38 A,Room 8N805,8600 Rockville Pike, Bethesda, MD 20894 USA.
EM bauer@ncbi.nlm.nih.gov
OI Marchler-Bauer, Aron/0000-0003-1516-0712
FU National Library of Medicine at the National Institutes of Health/DHHS
FX This work was funded by the Intramural Research Program of the National
   Library of Medicine at the National Institutes of Health/DHHS. Funding
   for open access charge: Intramural Research Program of the National
   Library of Medicine at National Institutes of Health/DHHS. Comments,
   suggestions, and questions are welcome and should be directed to:
   info@ncbi.nlm.nih.gov.
NR 13
TC 6
Z9 7
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1758-0463
J9 DATABASE-OXFORD
JI Database
PD MAR 20
PY 2012
AR bar058
DI 10.1093/database/bar058
PG 6
WC Mathematical & Computational Biology
SC Mathematical & Computational Biology
GA 954CB
UT WOS:000304922200002
ER

PT J
AU Harte, RA
   Farrell, CM
   Loveland, JE
   Suner, MM
   Wilming, L
   Aken, B
   Barrell, D
   Frankish, A
   Wallin, C
   Searle, S
   Diekhans, M
   Harrow, J
   Pruitt, KD
AF Harte, Rachel A.
   Farrell, Catherine M.
   Loveland, Jane E.
   Suner, Marie-Marthe
   Wilming, Laurens
   Aken, Bronwen
   Barrell, Daniel
   Frankish, Adam
   Wallin, Craig
   Searle, Steve
   Diekhans, Mark
   Harrow, Jennifer
   Pruitt, Kim D.
TI Tracking and coordinating an international curation effort for the CCDS
   Project
SO DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION
LA English
DT Article
ID MESSENGER-RNA DECAY; OPEN READING FRAMES; EXOME CAPTURE; TRANSLATION;
   INITIATION; SEQUENCE; GENOME; CONSERVATION; TRANSCRIPTS; PROKARYOTES
AB The Consensus Coding Sequence (CCDS) collaboration involves curators at multiple centers with a goal of producing a conservative set of high quality, protein-coding region annotations for the human and mouse reference genome assemblies. The CCDS data set reflects a 'gold standard' definition of best supported protein annotations, and corresponding genes, which pass a standard series of quality assurance checks and are supported by manual curation. This data set supports use of genome annotation information by human and mouse researchers for effective experimental design, analysis and interpretation. The CCDS project consists of analysis of automated whole-genome annotation builds to identify identical CDS annotations, quality assurance testing and manual curation support. Identical CDS annotations are tracked with a CCDS identifier (ID) and any future change to the annotated CDS structure must be agreed upon by the collaborating members. CCDS curation guidelines were developed to address some aspects of curation in order to improve initial annotation consistency and to reduce time spent in discussing proposed annotation updates. Here, we present the current status of the CCDS database and details on our procedures to track and coordinate our efforts. We also present the relevant background and reasoning behind the curation standards that we have developed for CCDS database treatment of transcripts that are nonsense-mediated decay (NMD) candidates, for transcripts containing upstream open reading frames, for identifying the most likely translation start codons and for the annotation of readthrough transcripts. Examples are provided to illustrate the application of these guidelines.
C1 [Farrell, Catherine M.; Wallin, Craig; Pruitt, Kim D.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
   [Harte, Rachel A.; Diekhans, Mark] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA.
   [Loveland, Jane E.; Suner, Marie-Marthe; Wilming, Laurens; Aken, Bronwen; Barrell, Daniel; Frankish, Adam; Searle, Steve; Harrow, Jennifer] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
RP Pruitt, KD (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA.
EM Pruitt@ncbi.nlm.nih.gov
OI Aken, Bronwen/0000-0002-3032-4095; Wilming, Laurens/0000-0002-4154-7358
FU National Institutes of Health, National Library of Medicine; National
   Human Genome Research Institute (NHGRI) [5U54 HG004555, 5U54HG00455-04];
   Wellcome Trust Sanger Institute [0244-03]; Wellcome Trust [WT077198,
   WT062023]
FX The work done at NCBI was supported by the Intramural Research Program
   of the National Institutes of Health, National Library of Medicine. Work
   done at UCSC has been funded with Federal funds from the National Human
   Genome Research Institute (NHGRI) for the ENCODE project (prime award
   5U54 HG004555, under subaward 0244-03 from the Wellcome Trust Sanger
   Institute). Work done at the Wellcome Trust Sanger Institute has been
   funded by the Wellcome Trust (grant number WT077198) for HAVANA and by
   the Wellcome Trust (grant number WT062023) and the National Human Genome
   Research Institute (grant number 5U54HG00455-04) for Ensembl. Funding
   for open access charge: the Intramural Research Program of the National
   Institutes of Health, National Library of Medicine.
NR 46
TC 18
Z9 18
U1 1
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1758-0463
J9 DATABASE-OXFORD
JI Database
PD MAR 20
PY 2012
AR bas008
DI 10.1093/database/bas008
PG 12
WC Mathematical & Computational Biology
SC Mathematical & Computational Biology
GA 954BO
UT WOS:000304920200006
ER

PT J
AU Hayamizu, TF
   de Coronado, S
   Fragoso, G
   Sioutos, N
   Kadin, JA
   Ringwald, M
AF Hayamizu, Terry F.
   de Coronado, Sherri
   Fragoso, Gilberto
   Sioutos, Nicholas
   Kadin, James A.
   Ringwald, Martin
TI The mouse-human anatomy ontology mapping project
SO DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION
LA English
DT Article
ID INFORMATION
AB The overall objective of the Mouse-Human Anatomy Project (MHAP) was to facilitate the mapping and harmonization of anatomical terms used for mouse and human models by Mouse Genome Informatics (MGI) and the National Cancer Institute (NCI). The anatomy resources designated for this study were the Adult Mouse Anatomy (MA) ontology and the set of anatomy concepts contained in the NCI Thesaurus (NCIt). Several methods and software tools were identified and evaluated, then used to conduct an in-depth comparative analysis of the anatomy ontologies. Matches between mouse and human anatomy terms were determined and validated, resulting in a highly curated set of mappings between the two ontologies that has been used by other resources. These mappings will enable linking of data from mouse and human. As the anatomy ontologies have been expanded and refined, the mappings have been updated accordingly. Insights are presented into the overall process of comparing and mapping between ontologies, which may prove useful for further comparative analyses and ontology mapping efforts, especially those involving anatomy ontologies. Finally, issues concerning further development of the ontologies, updates to the mapping files, and possible additional applications and significance were considered.
C1 [Hayamizu, Terry F.; Kadin, James A.; Ringwald, Martin] Jackson Lab, Bar Harbor, ME 04609 USA.
   [de Coronado, Sherri; Fragoso, Gilberto; Sioutos, Nicholas] NCI, Ctr Bioinformat, Rockville, MD 20852 USA.
RP Hayamizu, TF (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA.
EM terry.hayamizu@jax.org; martin.ringwald@jax.org
FU National Cancer Institute at the National Institute of Health, Cancer
   Biomedical Informatics Grid (caBIG(R)) [caBIG-VCDE-14-02-02]; National
   Institutes of Health, Eunice Kennedy Shriver National Institute of Child
   Health and Human Development [HD062499]; NIH [HD062499]; Vocabularies
   and Common Data Elements (VCDE) Workspace group
FX National Cancer Institute at the National Institute of Health, Cancer
   Biomedical Informatics Grid (caBIG (R)) (project number
   caBIG-VCDE-14-02-02); and National Institutes of Health, Eunice Kennedy
   Shriver National Institute of Child Health and Human Development (grant
   number HD062499). Funding for open access charge: NIH (grant HD062499).;
   We thank Connie Coon and Frank Hartel for contributions to the NCIt;
   Olivier Bodenreider and Songmao Zhang for their work aligning the
   ontologies using lexical and structural similarity approaches; Elena
   Beisswanger and the OAEI for helpful suggestions with regards to
   updating the mappings; Chris Mungall for assistance in making the
   mappings available through the OBO Foundry and, with his colleagues, for
   work on the Uberon ontology; Brian Davis and the Vocabularies and Common
   Data Elements (VCDE) Workspace group for support and assistance with
   caBIG (R) tasks; and our MGI and NCI colleagues for their advice and
   support.
NR 15
TC 5
Z9 5
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1758-0463
J9 DATABASE-OXFORD
JI Database
PD MAR 20
PY 2012
AR bar066
DI 10.1093/database/bar066
PG 10
WC Mathematical & Computational Biology
SC Mathematical & Computational Biology
GA 954CL
UT WOS:000304923700005
ER

PT J
AU Aimola, P
   Carmignani, M
   Volpe, AR
   Di Benedetto, A
   Claudio, L
   Waalkes, MP
   van Bokhoven, A
   Tokar, EJ
   Claudio, PP
AF Aimola, Pierpaolo
   Carmignani, Marco
   Volpe, Anna Rita
   Di Benedetto, Altomare
   Claudio, Luigi
   Waalkes, Michael P.
   van Bokhoven, Adrie
   Tokar, Erik J.
   Claudio, Pier Paolo
TI Cadmium Induces p53-Dependent Apoptosis in Human Prostate Epithelial
   Cells
SO PLOS ONE
LA English
DT Article
ID INDUCED MALIGNANT-TRANSFORMATION; WISTAR CRL-(WI)BR RATS; DOSE-RESPONSE
   ANALYSIS; NOBLE NBL/CR RAT; INJECTION SITE; C-JUN; PROLIFERATIVE
   LESIONS; TUMOR SUPPRESSION; OXIDATIVE STRESS; CANCER CELLS
AB Cadmium, a widespread toxic pollutant of occupational and environmental concern, is a known human carcinogen. The prostate is a potential target for cadmium carcinogenesis, although the underlying mechanisms are still unclear. Furthermore, cadmium may induce cell death by apoptosis in various cell types, and it has been hypothesized that a key factor in cadmium-induced malignant transformation is acquisition of apoptotic resistance. We investigated the in vitro effects produced by cadmium exposure in normal or tumor cells derived from human prostate epithelium, including RWPE-1 and its cadmium-transformed derivative CTPE, the primary adenocarcinoma 22Rv1 and CWR-R1 cells and LNCaP, PC-3 and DU145 metastatic cancer cell lines. Cells were treated for 24 hours with different concentrations of CdCl2 and apoptosis, cell cycle distribution and expression of tumor suppressor proteins were analyzed. Subsequently, cellular response to cadmium was evaluated after siRNA-mediated p53 silencing in wild type p53-expressing RWPE-1 and LNCaP cells, and after adenoviral p53 overexpression in p53-deficient DU145 and PC-3 cell lines. The cell lines exhibited different sensitivity to cadmium, and 24-hour exposure to different CdCl2 concentrations induced dose-and cell type-dependent apoptotic response and inhibition of cell proliferation that correlated with accumulation of functional p53 and overexpression of p21 in wild type p53-expressing cell lines. On the other hand, p53 silencing was able to suppress cadmium-induced apoptosis. Our results demonstrate that cadmium can induce p53-dependent apoptosis in human prostate epithelial cells and suggest p53 mutation as a possible contributing factor for the acquisition of apoptotic resistance in cadmium prostatic carcinogenesis.
C1 [Aimola, Pierpaolo; Di Benedetto, Altomare; Claudio, Pier Paolo] Marshall Univ, Dept Biochem & Microbiol, Joan C Edwards Sch Med, Huntington, WV 25755 USA.
   [Aimola, Pierpaolo; Carmignani, Marco; Volpe, Anna Rita; Di Benedetto, Altomare] Univ Aquila, Dept Basic & Appl Biol, I-67100 Laquila, Italy.
   [Claudio, Luigi] Fdn Senatore Pascale, Dept Urol, Natl Canc Inst, Naples, Italy.
   [Waalkes, Michael P.; Tokar, Erik J.] Natl Inst Environm Hlth Sci, Natl Toxicol Program, Res Triangle Pk, NC USA.
   [van Bokhoven, Adrie] Univ Colorado Denver, Dept Pathol, Aurora, CO USA.
   [Claudio, Pier Paolo] Marshall Univ, Dept Surg, Joan C Edwards Sch Med, Huntington, WV USA.
RP Aimola, P (reprint author), Marshall Univ, Dept Biochem & Microbiol, Joan C Edwards Sch Med, Huntington, WV 25755 USA.
EM claudiop@marshall.edu
OI Claudio, Pier Paolo/0000-0001-7790-1622
FU National Cancer Institute [CA131395, CA140024]; NIH [COBRE 5P20RR020180,
   WV-INBRE 5P20RR016477]; Cell Differentiation and Development Center
   (CDDC), Marshall University; NTP; NIEHS; Marshall University
   Biochemistry Department; Marshall University Microbiology & Surgery
   Department
FX The present studies were supported in part by the awards number CA131395
   and CA140024 from the National Cancer Institute, and in part by
   NIH-COBRE 5P20RR020180, WV-INBRE 5P20RR016477, and the Cell
   Differentiation and Development Center (CDDC), Marshall University (to
   PPC). These studies were also supported in part by the NTP and NIEHS.
   The content is solely the responsibility of the authors and does not
   necessarily represent the official views of the National Cancer
   Institute or the National Institute of Health. The funders had no role
   in study design, data collection and analysis, decision to publish, or
   preparation of the manuscript.; We gratefully acknowledge the Marshall
   University Biochemistry and Microbiology & Surgery Departments for their
   support.
NR 53
TC 26
Z9 30
U1 3
U2 12
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 20
PY 2012
VL 7
IS 3
AR e33647
DI 10.1371/journal.pone.0033647
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 939YB
UT WOS:000303855700053
PM 22448262
ER

PT J
AU Ledwaba, L
   Tavel, JA
   Khabo, P
   Maja, P
   Qin, J
   Sangweni, P
   Liu, X
   Follmann, D
   Metcalf, JA
   Orsega, S
   Baseler, B
   Neaton, JD
   Lane, HC
AF Ledwaba, Lotty
   Tavel, Jorge A.
   Khabo, Paul
   Maja, Patrick
   Qin, Jing
   Sangweni, Phumele
   Liu, Xiao
   Follmann, Dean
   Metcalf, Julia A.
   Orsega, Susan
   Baseler, Beth
   Neaton, James D.
   Lane, H. Clifford
CA Project Phidisa Biomarkers Team
TI Pre-ART Levels of Inflammation and Coagulation Markers Are Strong
   Predictors of Death in a South African Cohort with Advanced HIV Disease
SO PLOS ONE
LA English
DT Article
ID ACTIVE ANTIRETROVIRAL THERAPY; IMMUNODEFICIENCY-VIRUS-INFECTION;
   HIV-1-INFECTED PATIENTS; COMBINATION THERAPY; DECLINING MORBIDITY; EARLY
   MORTALITY; 1ST YEAR; AIDS; ADULTS; ERA
AB Background: Levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and D-dimer predict mortality in HIV patients on antiretroviral therapy (ART) with relatively preserved CD4+ T cell counts. We hypothesized that elevated pre-ART levels of these markers among patients with advanced HIV would be associated with an increased risk of death following the initiation of ART.
   Methods: Pre-ART plasma from patients with advanced HIV in South Africa was used to measure hsCRP, IL-6 and D-dimer. Using a nested case-control study design, the biomarkers were measured for 187 deaths and two controls matched on age, sex, clinical site, follow-up time and CD4+ cell counts. Odds ratios were estimated using conditional logistic regression. In addition, for a random sample of 100 patients, biomarkers were measured at baseline and 6 months following randomization to determine whether ART altered their levels.
   Results: Median baseline biomarkers levels for cases and controls, respectively, were 11.25 vs. 3.6 mg/L for hsCRP, 1.41 vs. 0.98 mg/L for D-dimer, and 9.02 vs. 4.20 pg/mL for IL-6 (all p<0.0001). Adjusted odds ratios for the highest versus lowest quartile of baseline biomarker levels were 3.5 (95% CI: 1.9-6.7) for hsCRP, 2.6 (95% CI 1.4-4.9) for D-dimer, and 3.8 (95% CI: 1.87.8) for IL-6. These associations were stronger for deaths that occurred more proximal to the biomarker measurements. Levels of D-dimer and IL-6, but not hsCRP, were significantly lower at month 6 after commencing ART compared to baseline (p<0.0001).
   Conclusions: Among patients with advanced HIV disease, elevated pre-ART levels of hsCRP, IL-6 and D-dimer are strongly associated with early mortality after commencing ART. Elevated levels of inflammatory and coagulation biomarkers may identify patients who may benefit from aggressive clinical monitoring after commencing ART. Further investigation of strategies to reduce biomarkers of inflammation and coagulation in patients with advanced HIV disease is warranted.
C1 [Ledwaba, Lotty; Khabo, Paul; Maja, Patrick; Sangweni, Phumele] Project Phidisa, Pretoria, South Africa.
   [Tavel, Jorge A.; Qin, Jing; Liu, Xiao; Follmann, Dean; Metcalf, Julia A.; Orsega, Susan; Lane, H. Clifford] NIH, Bethesda, MD 20892 USA.
   [Baseler, Beth] Frederick Inc, Sci Applicat Int Corp, Frederick, MD USA.
   [Neaton, James D.] Univ Minnesota, Minneapolis, MN USA.
RP Ledwaba, L (reprint author), Project Phidisa, Pretoria, South Africa.
EM lledwaba@phidisa.org
FU South African National Defence Force; United States National Institutes
   of Health; United States Department of Defense; SAIC-Frederick, Inc.;
   National Cancer Institute, National Institutes of Health
   [HHSN261200800001E]
FX Funding for the Phidisa Project, the Phidisa I and II studies, and this
   substudy were provided by the South African National Defence Force, the
   United States National Institutes of Health and the United States
   Department of Defense. SAIC-Frederick, Inc. helped fund the study
   through the employment of Beth Basseler and Xiao Liu who contributed to
   the study. This project has been funded in whole or in part with federal
   funds from the National Cancer Institute, National Institutes of Health,
   under contract no. HHSN261200800001E. The content of this publication
   does not necessarily reflect the views or policies of the Department of
   Health and Human Services, nor does mention of trade names, commercial
   products, or organizations imply endorsement by the U.S. Government. The
   funders had a role in study design, data collection and analysis,
   decision to publish, or preparation of the manuscript.
NR 32
TC 25
Z9 25
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 20
PY 2012
VL 7
IS 3
AR e24243
DI 10.1371/journal.pone.0024243
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 939YB
UT WOS:000303855700001
PM 22448211
ER

PT J
AU Mirabelli, MC
   London, SJ
   Charles, LE
   Pompeii, LA
   Wagenknecht, LE
AF Mirabelli, Maria C.
   London, Stephanie J.
   Charles, Luenda E.
   Pompeii, Lisa A.
   Wagenknecht, Lynne E.
TI Occupation and three-year incidence of respiratory symptoms and lung
   function decline: the ARIC Study
SO RESPIRATORY RESEARCH
LA English
DT Article
DE ARIC study; epidemiology; occupation; respiratory tract disease
ID OBSTRUCTIVE PULMONARY-DISEASE; ATHEROSCLEROSIS RISK; ONSET ASTHMA;
   POPULATION; EXPOSURE; ADULTS; STATEMENT; BURDEN; HEALTH
AB Background: Specific occupations are associated with adverse respiratory health. Inhalation exposures encountered in these jobs may place workers at risk of new-onset respiratory disease.
   Methods: We analyzed data from 8,967 participants from the Atherosclerosis Risk in Communities (ARIC) study, a longitudinal cohort study. Participants included in this analysis were free of chronic cough and phlegm, wheezing, asthma, chronic bronchitis, emphysema, and other chronic lung conditions at the baseline examination, when they were aged 45-64 years. Using data collected in the baseline and first follow-up examination, we evaluated associations between occupation and the three-year incidence of cough, phlegm, wheezing, and airway obstruction and changes in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) measured by spirometry. All associations were adjusted for age, cigarettes per day, race, smoking status, and study center.
   Results: During the approximately three-year follow-up, the percentage of participants developing chronic cough was 3%; chronic phlegm, 3%; wheezing, 3%; and airway obstruction, defined as FEV1 < lower limit of normal (LLN) and FEV1/FVC < LLN, 2%. The average annual declines in FEV1 and FVC were 56 mL and 66 mL, respectively, among men and 40 mL and 52 mL, respectively, among women. Relative to a referent category of managerial and administrative support occupations, elevated risks of new-onset chronic cough and chronic phlegm were observed for mechanics and repairers (chronic cough: RR: 1.81, 95% CI: 1.02, 3.21; chronic phlegm: RR: 2.10, 95% CI: 1.23, 3.57) and cleaning and building service workers (chronic cough: RR: 1.85, 95% CI: 1.01, 3.37; chronic phlegm: RR: 2.28, 95% CI: 1.27, 4.08). Despite the elevated risk of new-onset symptoms, employment in cleaning and building services was associated with attenuated lung function decline, particularly among men, who averaged annual declines in FEV1 and FVC of 14 mL and 23 mL, respectively, less than the declines observed in the referent population.
   Conclusions: Employment in mechanic and repair jobs and cleaning and building service occupations are associated with increased incidence of respiratory symptoms. Specific occupations affect the respiratory health of adults without pre-existing respiratory health symptoms and conditions, though long-term health consequences of inhalation exposures in these jobs remain largely unexplored.
C1 [Mirabelli, Maria C.] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC USA.
   [London, Stephanie J.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
   [Charles, Luenda E.] NIOSH, Biostat & Epidemiol Branch, Hlth Effects Lab Div, Ctr Dis Control & Prevent,Dept Hlth & Human Serv, Morgantown, WV USA.
   [Pompeii, Lisa A.] Univ Texas Houston, Sch Publ Hlth, Div Epidemiol Human Genet & Environm Sci, Houston, TX USA.
   [Wagenknecht, Lynne E.] Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA.
RP Mirabelli, MC (reprint author), Wake Forest Sch Med, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC USA.
EM mmirabel@wakehealth.edu
OI Mirabelli, Maria/0000-0002-3540-0085; London,
   Stephanie/0000-0003-4911-5290
FU Intramural NIH HHS; PHS HHS [HHSN268201100007C, HHSN268201100005C,
   HHSN268201100006C, HHSN268201100008C, HHSN268201100009C,
   HHSN268201100010C, HHSN268201100011C, HHSN268201100012C]
NR 26
TC 7
Z9 7
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1465-993X
J9 RESP RES
JI Respir. Res.
PD MAR 20
PY 2012
VL 13
AR 24
DI 10.1186/1465-9921-13-24
PG 9
WC Respiratory System
SC Respiratory System
GA 942PP
UT WOS:000304058600001
PM 22433119
ER

PT J
AU Linard, C
   Tatem, AJ
AF Linard, Catherine
   Tatem, Andrew J.
TI Large-scale spatial population databases in infectious disease research
SO INTERNATIONAL JOURNAL OF HEALTH GEOGRAPHICS
LA English
DT Review
DE Human population; Global; Infectious diseases; Spatial demography;
   Health metrics
ID PLASMODIUM-FALCIPARUM TRANSMISSION; TRANSMITTED HELMINTH INFECTIONS;
   HUMAN AFRICAN TRYPANOSOMIASIS; TICK-BORNE ENCEPHALITIS; SUB-SAHARAN
   AFRICA; MALARIA TRANSMISSION; GLOBAL DISTRIBUTION; AVIAN INFLUENZA;
   GREAT-BRITAIN; GEOSTATISTICAL PREDICTION
AB Modelling studies on the spatial distribution and spread of infectious diseases are becoming increasingly detailed and sophisticated, with global risk mapping and epidemic modelling studies now popular. Yet, in deriving populations at risk of disease estimates, these spatial models must rely on existing global and regional datasets on population distribution, which are often based on outdated and coarse resolution data. Moreover, a variety of different methods have been used to model population distribution at large spatial scales. In this review we describe the main global gridded population datasets that are freely available for health researchers and compare their construction methods, and highlight the uncertainties inherent in these population datasets. We review their application in past studies on disease risk and dynamics, and discuss how the choice of dataset can affect results. Moreover, we highlight how the lack of contemporary, detailed and reliable data on human population distribution in low income countries is proving a barrier to obtaining accurate large-scale estimates of population at risk and constructing reliable models of disease spread, and suggest research directions required to further reduce these barriers.
C1 [Linard, Catherine] Univ Libre Bruxelles, B-1050 Brussels, Belgium.
   [Linard, Catherine] Fonds Natl Rech Sci FRS FNRS, B-1000 Brussels, Belgium.
   [Tatem, Andrew J.] Univ Florida, Dept Geog, Gainesville, FL 32611 USA.
   [Tatem, Andrew J.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL 32610 USA.
   [Tatem, Andrew J.] NCI, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Linard, C (reprint author), Univ Libre Bruxelles, CP 160-12,Ave FD Roosevelt 50, B-1050 Brussels, Belgium.
EM linard.catherine@gmail.com
FU Wellcome Trust
NR 141
TC 24
Z9 25
U1 3
U2 28
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-072X
J9 INT J HEALTH GEOGR
JI Int. J. Health Geogr.
PD MAR 20
PY 2012
VL 11
AR 7
DI 10.1186/1476-072X-11-7
PG 13
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 930QR
UT WOS:000303154700001
PM 22433126
ER

PT J
AU Madonna, G
   Ullman, CD
   Gentilcore, G
   Palmieri, G
   Ascierto, PA
AF Madonna, Gabriele
   Ullman, Claudio Dansky
   Gentilcore, Giusy
   Palmieri, Giuseppe
   Ascierto, Paolo Antonio
TI NF-kappa B as potential target in the treatment of melanoma
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Review
DE NF-kappa B; Melanoma; NBD peptide; Bortezomib; Curcumin
ID NEMO-BINDING DOMAIN; STAGE-IV MELANOMA; MALIGNANT-MELANOMA; SIGNALING
   PATHWAY; PHASE-II; CELLS; KINASE; CURCUMIN; ACTIVATION; EXPRESSION
AB The RAS/MAP kinase pathway has attracted attention because activating mutations of the BRAF serine/threonine kinase was described in over 50% of melanomas. Very recently, selective and potent BRAF inhibitors have been developed. Several other signal transduction pathways have been found to be constitutively active or mutated in other subsets of melanoma tumors that are potentially targetable with new agents. Among these, NF kappa B is another pathway that melanoma tumors use to achieve survival, proliferation and resistance to apoptosis. Inhibition of NF kappa B activation appears to be a very promising option for anti-cancer therapies.
C1 [Madonna, Gabriele; Gentilcore, Giusy; Ascierto, Paolo Antonio] Ist Nazl Tumori Fdn, Unit Med Oncol & Innovat Therapy, Naples, Italy.
   [Ullman, Claudio Dansky] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
   [Palmieri, Giuseppe] CNR, Inst Biomol Chem, Sassari, Italy.
RP Ascierto, PA (reprint author), Ist Nazl Tumori Fdn, Unit Med Oncol & Innovat Therapy, Naples, Italy.
EM paolo.ascierto@gmail.com
NR 43
TC 49
Z9 52
U1 1
U2 7
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 MAR 20
PY 2012
VL 10
AR 53
DI 10.1186/1479-5876-10-53
PG 8
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 931ZS
UT WOS:000303258900002
PM 22433222
ER

PT J
AU Martinowich, K
   Cardinale, KM
   Schloesser, RJ
   Hsu, M
   Greig, NH
   Manji, HK
AF Martinowich, Keri
   Cardinale, Kathleen M.
   Schloesser, Robert J.
   Hsu, Michael
   Greig, Nigel H.
   Manji, Husseini K.
TI Acetylcholinesterase inhibition ameliorates deficits in motivational
   drive
SO BEHAVIORAL AND BRAIN FUNCTIONS
LA English
DT Article
DE Apathy; Motivation; Chronic stress; Cholinergic; FosB; c-fos; Nucleus
   accumbens; Basal forebrain
ID ALZHEIMERS-DISEASE; NEUROPSYCHIATRIC SYMPTOMS; CHOLINERGIC HYPOTHESIS;
   BEHAVIORAL-RESPONSES; STRESS; APATHY; DEPRESSION; ANHEDONIA; REWARD;
   THERAPY
AB Background: Apathy is frequently observed in numerous neurological disorders, including Alzheimer's and Parkinson's, as well as neuropsychiatric disorders including schizophrenia. Apathy is defined as a lack of motivation characterized by diminished goal-oriented behavior and self-initiated activity. This study evaluated a chronic restraint stress (CRS) protocol in modeling apathetic behavior, and determined whether administration of an anticholinesterase had utility in attenuating CRS-induced phenotypes.
   Methods: We assessed behavior as well as regional neuronal activity patterns using FosB immunohistochemistry after exposure to CRS for 6 h/d for a minimum of 21 d. Based on our FosB findings and recent clinical trials, we administered an anticholinesterase to evaluate attenuation of CRS-induced phenotypes.
   Results: CRS resulted in behaviors that reflect motivational loss and diminished emotional responsiveness. CRS-exposed mice showed differences in FosB accumulation, including changes in the cholinergic basal forebrain system. Facilitating cholinergic signaling ameliorated CRS-induced deficits in initiation and motivational drive and rescued immediate early gene activation in the medial septum and nucleus accumbens.
   Conclusions: Some CRS protocols may be useful for studying deficits in motivation and apathetic behavior. Amelioration of CRS-induced behaviors with an anticholinesterase supports a role for the cholinergic system in remediation of deficits in motivational drive.
C1 [Martinowich, Keri; Cardinale, Kathleen M.; Schloesser, Robert J.; Hsu, Michael] NIMH, Mood & Anxiety Disorders Program MAP, NIH, Bethesda, MD 20892 USA.
   [Greig, Nigel H.] NIA, Lab Neurosci, Sect Drug Design & Dev, NIH, Bethesda, MD 20892 USA.
   [Martinowich, Keri] Lieber Inst Brain Dev, Baltimore, MD 21205 USA.
   [Manji, Husseini K.] Johnson & Johnson Pharmaceut Res & Dev, Titusville, NJ 08560 USA.
RP Martinowich, K (reprint author), NIMH, Mood & Anxiety Disorders Program MAP, NIH, 35 Convent Dr,Bldg 35,Room 1C-1012, Bethesda, MD 20892 USA.
EM keri.martinowich@libd.org
RI Martinowich, Keri/F-9841-2012; 
OI Martinowich, Keri/0000-0002-5237-0789
FU National Institute of Mental Health (NIMH); National Institute on Aging
   (NIA)
FX Funding for this study was provided by the National Institute of Mental
   Health (NIMH) and the National Institute on Aging (NIA) Intramural
   Programs.
NR 46
TC 2
Z9 2
U1 1
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1744-9081
J9 BEHAV BRAIN FUNCT
JI Behav. Brain Funct.
PD MAR 20
PY 2012
VL 8
AR 15
DI 10.1186/1744-9081-8-15
PG 14
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 929HH
UT WOS:000303051400001
PM 22433906
ER

PT J
AU Alfano, CM
   Ganz, PA
   Rowland, JH
   Hahn, EE
AF Alfano, Catherine M.
   Ganz, Patricia A.
   Rowland, Julia H.
   Hahn, Erin E.
TI Cancer Survivorship and Cancer Rehabilitation: Revitalizing the Link
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID CLINICAL ONCOLOGY PROGRAM; BREAST-CANCER; PHYSICAL-ACTIVITY; SURVIVAL;
   HEALTH; INSTITUTE; WOMEN
C1 [Alfano, Catherine M.; Hahn, Erin E.] NCI, Off Canc Survivorship, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
   [Ganz, Patricia A.] Univ Calif Los Angeles, Sch Publ Hlth, Sch Med, Los Angeles, CA 90024 USA.
   [Ganz, Patricia A.; Hahn, Erin E.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA.
RP Alfano, CM (reprint author), NCI, Off Canc Survivorship, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
OI Hahn, Erin E/0000-0002-8419-2331
NR 38
TC 43
Z9 43
U1 0
U2 5
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 MAR 20
PY 2012
VL 30
IS 9
BP 904
EP 906
DI 10.1200/JCO.2011.37.1674
PG 3
WC Oncology
SC Oncology
GA 923OK
UT WOS:000302628400007
PM 22355063
ER

PT J
AU Kleinerman, RA
   Yu, CL
   Little, MP
   Li, Y
   Abramson, D
   Seddon, J
   Tucker, MA
AF Kleinerman, Ruth A.
   Yu, Chu-ling
   Little, Mark P.
   Li, Yi
   Abramson, David
   Seddon, Johanna
   Tucker, Margaret A.
TI Variation of Second Cancer Risk by Family History of Retinoblastoma
   Among Long-Term Survivors
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID HEREDITARY RETINOBLASTOMA; RB1 MUTATIONS; FOLLOW-UP; RADIOTHERAPY;
   MORTALITY; SARCOMAS; GENE
AB Purpose
   To evaluate the risk of second cancer (SC) in long-term survivors of retinoblastoma (Rb) according to classification of germline mutation, based on family history of Rb and laterality.
   Patients and Methods
   We assembled a cohort of 1,852 1-year survivors of Rb (bilateral, n = 1,036; unilateral, n = 816). SCs were ascertained by medical records and self-reports and confirmed by pathology reports. Classification of RB1 germline mutation, inherited or de novo, was inferred by laterality of Rb and positive family history of Rb. Standardized incidence ratios and cumulative incidence for all SCs combined and for soft tissue sarcomas, bone cancers, and melanoma were calculated. The influence of host-and therapy-related risk factors for SC was assessed by Poisson regression for bilateral survivors.
   Results
   We observed a relative risk (RR) of 1.37 (95% CI, 1.00 to 1.86) for SCs in bilateral survivors associated with a family history of Rb, adjusted for treatment, age, and length of follow-up. The risk for melanoma was significantly elevated for survivors with a family history of Rb (RR, 3.08; 95% CI, 1.23 to 7.16), but risks for bone or soft tissue sarcomas were not elevated. The cumulative incidence of SCs 50 years after diagnosis of bilateral Rb, with adjustment for competing risk of death, was significantly higher for survivors with a family history (47%; 95% CI, 35% to 59%) than survivors without a family history (38%; 95% CI, 32% to 44%; P = .004).
   Conclusion
   Rb survivors with bilateral disease and an inherited germline mutation are at slightly higher risk of an SC compared with those with a de novo germline mutation, in particular melanoma, perhaps because of shared genetic alterations. J Clin Oncol 30: 950-957. (C) 2012 by American Society of Clinical Oncology
C1 [Kleinerman, Ruth A.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA.
   [Li, Yi] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Seddon, Johanna] Tufts Univ New England Med Ctr, Boston, MA USA.
   [Abramson, David] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
RP Kleinerman, RA (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, EPS 7044,6120 Execut Blvd, Rockville, MD 20852 USA.
EM Kleinerr@mail.nih.gov
RI Tucker, Margaret/B-4297-2015; 
OI Kleinerman, Ruth/0000-0001-7415-2478; Little, Mark/0000-0003-0980-7567
FU National Institutes of Health; National Cancer Institute
FX Supported by the Intramural Research Program of the National Institutes
   of Health and the National Cancer Institute.
NR 27
TC 31
Z9 32
U1 0
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 MAR 20
PY 2012
VL 30
IS 9
BP 950
EP 957
DI 10.1200/JCO.2011.37.0239
PG 8
WC Oncology
SC Oncology
GA 923OK
UT WOS:000302628400014
PM 22355046
ER

PT J
AU Szabo, A
   Zhou, HX
AF Szabo, Attila
   Zhou, Huan-Xiang
TI Role of Diffusion in the Kinetics of Reversible Enzyme-catalyzed
   Reactions
SO BULLETIN OF THE KOREAN CHEMICAL SOCIETY
LA English
DT Article
DE Diffusion-influenced reaction; Enzyme-catalyzed reaction;
   Michaelis-Menten kinetics
ID DEPENDENT RATE COEFFICIENTS; MICHAELIS-MENTEN KINETICS; ASYMPTOTIC
   RELAXATION; SIMULATION; TRANSPORT; BINDING
AB The accurate expression for the steady-state velocity of an irreversible enzyme-catalyzed reaction obtained by Shin and co-workers (J. Chem. Phys.. 2001, 115, 1455) is generalized to allow for the rebinding of the product. The amplitude of the power-law (t(-1/2)) relaxation of the free- and bound-enzyme concentrations to steady-state values is expressed in terms of the steady-state velocity and the intrinsic (chemical) rate constants. This result is conjectured to be exact, even though our expression for the steady-state velocity in terms of microscopic parameters is only approximate.
C1 [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.
   [Szabo, Attila] Natl Inst Digest & Kidney Dis, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Zhou, HX (reprint author), Florida State Univ, Dept Phys, Tallahassee, FL 32306 USA.
EM hzhou@fsu.edu
RI Szabo, Attila/H-3867-2012; Zhou, Huan-Xiang/M-5170-2016
OI Zhou, Huan-Xiang/0000-0001-9020-0302
FU NIH, National Institute of Diabetes and Digestive and Kidney Diseases
   [GM58187]; NIH [GM58187]
FX We thank Noam Agmon for his comments on the manuscript. This study was
   supported by the Intramural Research Program of the NIH, National
   Institute of Diabetes and Digestive and Kidney Diseases, and by grant
   GM58187 from the NIH.
NR 15
TC 11
Z9 11
U1 5
U2 22
PU KOREAN CHEMICAL SOC
PI SEOUL
PA 635-4 YEOGSAM-DONG, KANGNAM-GU, SEOUL 135-703, SOUTH KOREA
SN 0253-2964
J9 B KOREAN CHEM SOC
JI Bull. Korean Chem. Soc.
PD MAR 20
PY 2012
VL 33
IS 3
BP 925
EP 928
DI 10.5012/bkcs.2012.33.3.925
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA 917RM
UT WOS:000302196300028
PM 23418399
ER

PT J
AU Kim, W
   Lao, QZ
   Shin, YK
   Carlson, OD
   Lee, EK
   Gorospe, M
   Kulkarni, RN
   Egan, JM
AF Kim, Wook
   Lao, Qizong
   Shin, Yu-Kyong
   Carlson, Olga D.
   Lee, Eun Kyung
   Gorospe, Myriam
   Kulkarni, Rohit N.
   Egan, Josephine M.
TI Cannabinoids Induce Pancreatic beta-Cell Death by Directly Inhibiting
   Insulin Receptor Activation
SO SCIENCE SIGNALING
LA English
DT Article
ID FORKHEAD TRANSCRIPTION FACTOR; ENDOCANNABINOID SYSTEM; CB1 RECEPTOR;
   CYTOPLASMIC LOCALIZATION; DIABETES-MELLITUS; TYROSINE RESIDUES; CYCLE
   PROGRESSION; INDUCED APOPTOSIS; CANCER CELLS; LIPID RAFTS
AB Cannabinoid 1 (CB1) receptors have been previously detected in pancreatic beta cells, where they attenuate insulin action. We now report that CB1 receptors form a heteromeric complex with insulin receptors and the heterotrimeric guanosine triphosphate-binding protein alpha subunit G alpha(i). G alpha(i) inhibited the kinase activity of the insulin receptor in beta cells by directly binding to the activation loop in the tyrosine kinase domain of the receptor. Consequently, phosphorylation of proapoptotic protein Bad was reduced and its apoptotic activity was stimulated, leading to beta-cell death. Pharmacological blockade or genetic deficiency of CB1 receptors enhanced insulin receptor signaling after injury, leading to reduced blood glucose concentrations and activation of Bad, which increased beta-cell survival. These findings provide direct evidence of physical and functional interactions between CB1 and insulin receptors and suggest a mechanism whereby peripherally acting CB1 receptor antagonists improve insulin action in insulin-sensitive tissues independent of the other metabolic effects of CB1 receptors.
C1 [Kim, Wook; Lao, Qizong; Shin, Yu-Kyong; Carlson, Olga D.; Gorospe, Myriam; Egan, Josephine M.] NIA, NIH, Baltimore, MD 21224 USA.
   [Lee, Eun Kyung] Catholic Univ Korea, Coll Med, Dept Biochem, Seoul 137701, South Korea.
   [Kulkarni, Rohit N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Islet Cell Biol & Regenerat Med, Boston, MA 02215 USA.
   [Kulkarni, Rohit N.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA.
RP Egan, JM (reprint author), NIA, NIH, Baltimore, MD 21224 USA.
EM eganj@grc.nia.nih.gov
FU NIA/NIH; National Research Foundation of Korea (NRF); Korea government
   (MEST) [20110013116]; Catholic Medical Center Research Foundation; NIH
   [RO1 DK 67536, 68721]
FX This work was supported by the Intramural Research Program of the
   NIA/NIH. E.K.L. is supported by the National Research Foundation of
   Korea (NRF) grant funded by the Korea government (MEST) (20110013116)
   and the Catholic Medical Center Research Foundation. R.N.K. is supported
   by NIH RO1 DK 67536 and 68721.
NR 57
TC 26
Z9 26
U1 1
U2 4
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1937-9145
J9 SCI SIGNAL
JI Sci. Signal.
PD MAR 20
PY 2012
VL 5
IS 216
AR ra23
DI 10.1126/scisignal.2002519
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 916RQ
UT WOS:000302121300003
PM 22434934
ER

PT J
AU Lu, JH
   Sun, PD
AF Lu, Jinghua
   Sun, Peter D.
TI The Structure of the TLR5-Flagellin Complex: A New Mode of Pathogen
   Detection, Conserved Receptor Dimerization for Signaling
SO SCIENCE SIGNALING
LA English
DT Article
ID TOLL-LIKE RECEPTORS; TLR4-MD-2 COMPLEX; CRYSTAL-STRUCTURE; RECOGNITION;
   FLAGELLIN
AB Knowledge about how Toll-like receptors (TLRs) recognize pathogenic ligands is critical to understanding how these receptors are activated and to designing therapeutic compounds that target this family of receptors for inflammatory diseases. The crystal structure of TLR5 in complex with its bacterial ligand flagellin revealed that the ligand-binding mode for TLR5 is distinct from that of previously characterized TLRs. Nevertheless, like other TLRs, TLR5 forms a dimer in response to ligand binding. This work contributes to our current knowledge of TLR function and further demonstrates the ability of TLRs to couple versatile ligand recognition to a conserved receptor signaling mechanism.
C1 [Lu, Jinghua; Sun, Peter D.] NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
RP Sun, PD (reprint author), NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA.
EM psun@nih.gov
NR 11
TC 7
Z9 7
U1 2
U2 12
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1937-9145
J9 SCI SIGNAL
JI Sci. Signal.
PD MAR 20
PY 2012
VL 5
IS 216
AR pe11
DI 10.1126/scisignal.2002963
PG 2
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 916RQ
UT WOS:000302121300001
PM 22434932
ER

PT J
AU McAlister, GC
   Russell, JD
   Rumachik, NG
   Hebert, AS
   Syka, JEP
   Geer, LY
   Westphall, MS
   Pagliarini, DJ
   Coon, JJ
AF McAlister, Graeme C.
   Russell, Jason D.
   Rumachik, Neil G.
   Hebert, Alexander S.
   Syka, John E. P.
   Geer, Lewis Y.
   Westphall, Michael S.
   Pagliarini, David J.
   Coon, Joshua J.
TI Analysis of the Acidic Proteome with Negative Electron-Transfer
   Dissociation Mass Spectrometry
SO ANALYTICAL CHEMISTRY
LA English
DT Article
ID PHASE ION/ION REACTIONS; DETACHMENT DISSOCIATION; SEARCH ALGORITHM;
   PEPTIDES; ANIONS; CLEAVAGES; BACKBONE; HISTIDINE; IDENTIFICATIONS;
   FRAGMENTATIONS
AB We describe the first implementation of negative electron-transfer dissociation (NETD) on a hybrid ion trap-orbitrap mass spectrometer and its application to high-throughput sequencing of peptide anions. NETD, coupled with high pH separations, negative electrospray ionization (ESI), and an NETD compatible version of OMSSA, is part of a complete workflow that includes the formation, interrogation, and sequencing of peptide anions. Together these interlocking pieces facilitated the identification of more than 2000 unique peptides from Saccharomyces cerevisiae representing the most comprehensive analysis of peptide anions by tandem mass spectrometry to date. The same S. cerevisiae samples were interrogated using traditional, positive modes of peptide LC-MS/MS analysis (e.g., acidic LC separations, positive ESI, and collision activated dissociation), and the resulting peptide identifications of the different workflows were compared. Due to a decreased flux of peptide anions and a tendency to produce lowly charged precursors, the NETD-based LC-MS/MS workflow was not as sensitive as the positive mode methods. However, the use of NETD readily permits access to underrepresented acidic portions of the proteome by identifying peptides that tend to have lower pI values. As such, NETD improves sequence coverage, filling out the acidic portions of proteins that are often overlooked by the other methods.
C1 [McAlister, Graeme C.; Russell, Jason D.; Rumachik, Neil G.; Coon, Joshua J.] Univ Wisconsin, Dept Chem, Madison, WI 53706 USA.
   [Pagliarini, David J.] Univ Wisconsin, Dept Biochem, Madison, WI 53705 USA.
   [Hebert, Alexander S.; Coon, Joshua J.] Univ Wisconsin, Dept Biomol Chem, Madison, WI USA.
   [Westphall, Michael S.; Coon, Joshua J.] Univ Wisconsin, Genome Ctr Wisconsin, Madison, WI USA.
   [Geer, Lewis Y.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
   [Syka, John E. P.] Thermo Fisher Sci, San Jose, CA USA.
RP Coon, JJ (reprint author), Univ Wisconsin, Dept Chem, 1101 Univ Ave, Madison, WI 53706 USA.
EM jcoon@chem.wisc.edu
RI Geer, Lewis/H-2714-2014; 
OI Pagliarini, Dave/0000-0002-0001-0087
FU Thermo Fisher Scientific; National Institutes of Health [R01GM080148];
   NIH, National Library of Medicine
FX G.C.M. and J.D.R. contributed equally to this work. We thank AJ Bureta
   for figure design, Craig D. Wenger and Derek J. Bailey for assistance
   with data analysis, Jae C. Schwartz for helpful discussions, and Sarah
   Jacob for aid in manuscript preparation. We are grateful to Thermo
   Fisher Scientific and the National Institutes of Health (R01GM080148 to
   J.J.C.) for providing funding for this work. This research was supported
   in part by the Intramural Research Program of the NIH, National Library
   of Medicine.
NR 49
TC 21
Z9 21
U1 0
U2 40
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0003-2700
EI 1520-6882
J9 ANAL CHEM
JI Anal. Chem.
PD MAR 20
PY 2012
VL 84
IS 6
BP 2875
EP 2882
DI 10.1021/ac203430u
PG 8
WC Chemistry, Analytical
SC Chemistry
GA 910KB
UT WOS:000301634500038
PM 22335612
ER

PT J
AU Waterfall, JJ
   Meltzer, PS
AF Waterfall, Joshua J.
   Meltzer, Paul S.
TI Targeting Epigenetic Misregulation in Synovial Sarcoma
SO CANCER CELL
LA English
DT Editorial Material
ID TUMORS
AB Like many sarcomas, synovial sarcoma is driven by a characteristic oncogenic transcription factor fusion, SS18-SSX. In this issue of Cancer Cell, Su et al. elucidate the protein partners necessary for target gene misregulation and demonstrate a direct effect of histone deacetylase inhibitors on the SS18-SSX complex composition, expression misregulation, and apoptosis.
C1 [Waterfall, Joshua J.; Meltzer, Paul S.] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Meltzer, PS (reprint author), NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
EM pmeltzer@mail.nih.gov
NR 10
TC 4
Z9 4
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
J9 CANCER CELL
JI Cancer Cell
PD MAR 20
PY 2012
VL 21
IS 3
BP 323
EP 324
DI 10.1016/j.ccr.2012.02.023
PG 2
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 913YH
UT WOS:000301912800004
PM 22439927
ER

PT J
AU Liu, ZH
   Thiele, CJ
AF Liu, Zhihui
   Thiele, Carol J.
TI ALK and MYCN: When Two Oncogenes Are Better than One
SO CANCER CELL
LA English
DT Editorial Material
ID NEUROBLASTOMA; EXPRESSION; GENES
AB Mutations of ALK are frequently observed in MYCN-amplified neuroblastomas and correlate with poor clinical outcome, but how these oncogenes cooperate in neuroblastoma development remains unclear. In this issue of Cancer Cell, Zhu et al. describe a mechanism by which ALK and MYCN synergistically induce neuroblastoma in the zebrafish model system.
C1 [Liu, Zhihui; Thiele, Carol J.] NCI, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Thiele, CJ (reprint author), NCI, Pediat Oncol Branch, Ctr Canc Res, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM ct47a@nih.gov
FU Intramural NIH HHS [ZIA BC010788-04]
NR 10
TC 2
Z9 3
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
J9 CANCER CELL
JI Cancer Cell
PD MAR 20
PY 2012
VL 21
IS 3
BP 325
EP 326
DI 10.1016/j.ccr.2012.03.004
PG 2
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 913YH
UT WOS:000301912800005
PM 22439928
ER

PT J
AU Cai, Q
   Zakaria, HM
   Simone, A
   Sheng, ZH
AF Cai, Qian
   Zakaria, Hesham Mostafa
   Simone, Anthony
   Sheng, Zu-Hang
TI Spatial Parkin Translocation and Degradation of Damaged Mitochondria via
   Mitophagy in Live Cortical Neurons
SO CURRENT BIOLOGY
LA English
DT Article
ID NEURODEGENERATIVE DISEASES; OXIDATIVE STRESS; PINK1; TRANSPORT;
   DYNAMICS; DEPOLARIZATION; DEGENERATION; RECRUITMENT; DYSFUNCTION;
   DROSOPHILA
AB Mitochondria are essential for neuronal survival and function. Proper degradation of aged and damaged mitochondria through mitophagy is a key cellular pathway for mitochondrial quality control. Recent studies have indicated that PINK1/Parkin-mediated pathways ensure mitochondrial integrity and function [1-8]. Trans location of Parkin to damaged mitochondria induces mitophagy in many nonneuronal cell types [9-16]. However, evidence showing Parkin translocation in primary neurons is controversial [9, 15, 17, 18], leaving unanswered questions as to how and where Parkin-mediated mitophagy occurs in neurons. Here, we report the unique process of dissipating mitochondrial Delta Psi(m)-induced and Parkin-mediated mitophagy in mature cortical neurons. Compared with nonneuronal cells, neuronal mitophagy is a much slower and compartmentally restricted process, coupled with reduced anterograde mitochondria! transport. Parkin-targeted mitochondria are accumulated in the somatodendritic regions where mature lysosomes are predominantly located. Time-lapse imaging shows dynamic formation and elimination of Parkin- and LC3-ring-like structures surrounding depolarized mitochondria through the autophagy-lysosomal pathway in the soma. Knocking down Parkin in neurons impairs the elimination of dysfunctional mitochondria. Thus, our study provides neuronal evidence for dynamic and spatial Parkin-mediated mitophagy, which will help us understand whether altered mitophagy contributes to pathogenesis of several major neurodegenerative diseases characterized by mitochondrial dysfunction and impaired transport.
C1 [Cai, Qian; Zakaria, Hesham Mostafa; Simone, Anthony; Sheng, Zu-Hang] Natl Inst Neurol Disorders & Stroke, Synapt Funct Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Cai, Qian] Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ 08854 USA.
   [Zakaria, Hesham Mostafa] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20814 USA.
RP Cai, Q (reprint author), Natl Inst Neurol Disorders & Stroke, Synapt Funct Sect, Porter Neurosci Res Ctr, NIH, Room 2B-215,35 Convent Dr, Bethesda, MD 20892 USA.
EM cai@biology.rutgers.edu; shengz@ninds.nih.gov
FU NINDS; NIH; Howard Hughes Medical Institute-NIH
FX We thank R.J. Youle for helpful discussions; R.J. Youle, B. Lu, and M.J.
   LaVoie for Parkin DNA constructs; the members of the Sheng laboratory
   for technical assistance and helpful discussions; and S. Yang and D.
   Schoenberg for editing. This work was supported by the Intramural
   Research Program of NINDS, NIH (Z-H.S.), the NIH Pathway to Independence
   Award K99 (Q.C.), and Howard Hughes Medical Institute-NIH Research
   Scholars Program (H.M.Z.)
NR 30
TC 100
Z9 101
U1 0
U2 14
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 MAR 20
PY 2012
VL 22
IS 6
BP 545
EP 552
DI 10.1016/j.cub.2012.02.005
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 913PW
UT WOS:000301890900026
PM 22342752
ER

PT J
AU Wikstrom, M
   Hummer, G
AF Wikstrom, Marten
   Hummer, Gerhard
TI Stoichiometry of proton translocation by respiratory complex I and its
   mechanistic implications
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE cell respiration; proton pumping; conformational changes;
   phosphorylation potential
ID NADH-QUINONE OXIDOREDUCTASE; MITOCHONDRIAL OXIDATIVE-PHOSPHORYLATION;
   CONSERVED CHARGED RESIDUES; ESCHERICHIA-COLI NDH-1; RAT-LIVER
   MITOCHONDRIA; MEMBRANE DOMAIN; ELECTRON-TRANSFER; SUBUNIT; UBIQUINONE;
   REDUCTASE
AB Complex I (NADH-ubiquinone oxidoreductase) in the respiratory chain of mitochondria and several bacteria functions as a redox-driven proton pump that contributes to the generation of the protonmotive force across the inner mitochondrial or bacterial membrane and thus to the aerobic synthesis of ATP. The stoichiometry of proton translocation is thought to be 4 H+ per NADH oxidized (2 e(-)). Here we show that a H+/2 e(-) ratio of 3 appears more likely on the basis of the recently determined H+/ATP ratio of the mitochondrial F1Fo-ATP synthase of animal mitochondria and of a set of carefully determined ATP/2 e(-) ratios for different segments of the mitochondrial respiratory chain. This lower H+/2 e(-) ratio of 3 is independently supported by thermodynamic analyses of experiments with both mitochondria and submitochondrial particles. A reduced H+/2 e(-) stoichiometry of 3 has important mechanistic implications for this proton pump. In a rough mechanistic model, we suggest a concerted proton translocation mechanism in the three homologous and tightly packed antiporter-like subunits L, M, and N of the proton-translocating membrane domain of complex I.
C1 [Wikstrom, Marten] Univ Helsinki, Helsinki Bioenerget Grp, Inst Biotechnol, FI-00014 Helsinki, Finland.
   [Hummer, Gerhard] NIDDK, Lab Chem Phys, NIH, Bethesda, MD 20892 USA.
RP Wikstrom, M (reprint author), Univ Helsinki, Helsinki Bioenerget Grp, Inst Biotechnol, FI-00014 Helsinki, Finland.
EM Marten.Wikstrom@Helsinki.Fi
RI Hummer, Gerhard/A-2546-2013
OI Hummer, Gerhard/0000-0001-7768-746X
FU National Institute of Diabetes and Digestive and Kidney Diseases,
   National Institutes of Health; Sigrid Juselius Foundation; Biocentrum
   Helsinki; Academy of Finland
FX G.H. is supported by the Intramural Research Program of the National
   Institute of Diabetes and Digestive and Kidney Diseases, National
   Institutes of Health. M. W. is supported by grants from the Sigrid
   Juselius Foundation, Biocentrum Helsinki, and the Academy of Finland.
NR 41
TC 46
Z9 46
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 MAR 20
PY 2012
VL 109
IS 12
BP 4431
EP 4436
DI 10.1073/pnas.1120949109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 911JH
UT WOS:000301712600024
PM 22392981
ER

PT J
AU Hoadley, KA
   Xue, YT
   Ling, C
   Takata, M
   Wang, WD
   Keck, JL
AF Hoadley, Kelly A.
   Xue, Yutong
   Ling, Chen
   Takata, Minoru
   Wang, Weidong
   Keck, James L.
TI Defining the molecular interface that connects the Fanconi anemia
   protein FANCM to the Bloom syndrome dissolvasome
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE DNA recombination; X-ray crystallography
ID HOLLIDAY JUNCTION DISSOLVASOME; MAINTAIN GENOME STABILITY; DAMAGE
   RESPONSE NETWORK; FOLD-CONTAINING PROTEIN; HOMOLOGOUS RECOMBINATION;
   ESSENTIAL COMPONENT; SYNDROME HELICASE; REPLICATION-FORK; RECQ
   HELICASES; DNA-REPAIR
AB The RMI subcomplex (RMI1/RMI2) functions with the BLM helicase and topoisomerase IIIa in a complex called the "dissolvasome," which separates double-Holliday junction DNA structures that can arise during DNA repair. This activity suppresses potentially harmful sister chromatid exchange (SCE) events in wild-type cells but not in cells derived from Bloom syndrome patients with inactivating BLM mutations. The RMI subcomplex also associates with FANCM, a component of the Fanconi anemia (FA) core complex that is important for repair of stalled DNA replication forks. The RMI/FANCM interface appears to help coordinate dissolvasome and FA core complex activities, but its precise role remains poorly understood. Here, we define the structure of the RMI/FANCM interface and investigate its roles in coordinating cellular DNA-repair activities. The X-ray crystal structure of the RMI core complex bound to a well-conserved peptide from FANCM shows that FANCM binds to both RMI proteins through a hydrophobic "knobs-into-holes" packing arrangement. The RMI/FANCM interface is shown to be critical for interaction between the components of the dissolvasome and the FA core complex. FANCM variants that substitute alanine for key interface residues strongly destabilize the complex in solution and lead to increased SCE levels in cells that are similar to those observed in blm- or fancm-deficient cells. This study provides a molecular view of the RMI/FANCM complex and highlights a key interface utilized in coordinating the activities of two critical eukaryotic DNA-damage repair machines.
C1 [Xue, Yutong; Ling, Chen; Wang, Weidong] NIA, Genet Lab, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
   [Hoadley, Kelly A.; Keck, James L.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Biomol Chem, Madison, WI 53706 USA.
   [Takata, Minoru] Kyoto Univ, Lab DNA Damage Signaling, Dept Late Effects Studies, Ctr Radiat Biol, Kyoto 6068501, Japan.
RP Wang, WD (reprint author), NIA, Genet Lab, NIH, Biomed Res Ctr, 251 Bayview Blvd,10B113, Baltimore, MD 21224 USA.
EM WangW@grc.nia.nih.gov; jlkeck@wisc.edu
FU National Institutes of Health (NIH) [GM068061, GM07215]; National
   Institute on Aging [Z01 AG000657-08]
FX We thank Advanced Photon Source staff (LS-CAT beamline) and Ken Satyshur
   for assistance with data collection and members of the Keck Lab for
   critical reading of this manuscript. We thank members of the Denu lab
   for their assistance with peptide purification and mass spectrometry.
   This work was funded by a grant from the National Institutes of Health
   (NIH) (GM068061, J.L.K.) and by the Intramural Research Program of the
   National Institute on Aging (Z01 AG000657-08, W. W.). K. A. H. was
   supported in part by an NIH training grant in Molecular Biosciences
   (GM07215).
NR 30
TC 24
Z9 24
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 MAR 20
PY 2012
VL 109
IS 12
BP 4437
EP 4442
DI 10.1073/pnas.1117279109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 911JH
UT WOS:000301712600025
PM 22392978
ER

PT J
AU Qiang, W
   Yau, WM
   Luo, YQ
   Mattson, MP
   Tycko, R
AF Qiang, Wei
   Yau, Wai-Ming
   Luo, Yongquan
   Mattson, Mark P.
   Tycko, Robert
TI Antiparallel beta-sheet architecture in Iowa-mutant beta-amyloid fibrils
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE Alzheimer's disease; amyloid structure; solid state NMR
ID SOLID-STATE NMR; NUCLEAR-MAGNETIC-RESONANCE; ROTATING SOLIDS;
   SUPRAMOLECULAR STRUCTURE; DISTANCE MEASUREMENTS; STRUCTURAL FEATURES;
   ELECTRON-MICROSCOPY; CHEMICAL-SHIFTS; POLAR ZIPPERS; PARALLEL
AB Wild-type, full-length (40- and 42-residue) amyloid beta-peptide (A beta) fibrils have been shown by a variety of magnetic resonance techniques to contain cross-beta structures in which the beta-sheets have an in-register parallel supramolecular organization. In contrast, recent studies of fibrils formed in vitro by the Asp23-to-Asn mutant of 40-residue A beta (D23N-A beta(1-40)), which is associated with early onset neurodegeneration, indicate that D23N-A beta(1-40) fibrils can contain either parallel or antiparallel beta-sheets. We report a protocol for producing structurally pure antiparallel D23N-A beta(1-40) fibril samples and a series of solid state nuclear magnetic resonance and electron microscopy measurements that lead to a specific model for the antiparallel D23N-A beta(1-40) fibril structure. This model reveals how both parallel and antiparallel cross-beta structures can be constructed from similar peptide monomer conformations and stabilized by similar sets of interactions, primarily hydrophobic in nature. We find that antiparallel D23N-A beta(1-40) fibrils are thermodynamically metastable with respect to conversion to parallel structures, propagate less efficiently than parallel fibrils in seeded fibril growth, and therefore must nucleate more efficiently than parallel fibrils in order to be observable. Experiments in neuronal cell cultures indicate that both antiparallel and parallel D23N-A beta(1-40) fibrils are cytotoxic. Thus, our antiparallel D23N-A beta(1-40) fibril model represents a specific "toxic intermediate" in the aggregation process of a disease-associated A beta mutant.
C1 [Qiang, Wei; Yau, Wai-Ming; Tycko, Robert] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
   [Luo, Yongquan; Mattson, Mark P.] NIA, Neurosci Lab, Biomed Res Ctr, Baltimore, MD 21224 USA.
RP Tycko, R (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA.
EM robertty@mail.nih.gov
RI Mattson, Mark/F-6038-2012; Qiang, Wei/I-1053-2012
FU National Institute of Diabetes and Digestive and Kidney Diseases;
   National Institute on Aging, within the National Institutes of Health
FX This work was supported by the Intramural Research Programs of the
   National Institute of Diabetes and Digestive and Kidney Diseases and the
   National Institute on Aging, within the National Institutes of Health.
NR 51
TC 124
Z9 125
U1 5
U2 79
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 MAR 20
PY 2012
VL 109
IS 12
BP 4443
EP 4448
DI 10.1073/pnas.1111305109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 911JH
UT WOS:000301712600026
PM 22403062
ER

PT J
AU Ma, XF
   Kovacs, M
   Conti, MA
   Wang, AB
   Zhang, YF
   Sellers, JR
   Adelstein, RS
AF Ma, Xuefei
   Kovacs, Mihaly
   Conti, Mary Anne
   Wang, Aibing
   Zhang, Yingfan
   Sellers, James R.
   Adelstein, Robert S.
TI Nonmuscle myosin II exerts tension but does not translocate actin in
   vertebrate cytokinesis
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE cortical tension; myosin II kinetics; graded myosin knockdown;
   motor-impaired myosin; myosin-actin binding
ID MYH9-RELATED DISEASE; FECHTNER-SYNDROME; FISSION YEAST; CELL-ADHESION;
   DYNAMICS; CONTRACTILE; MUTATIONS; MECHANISM; FURROW; INHIBITION
AB During vertebrate cytokinesis it is thought that contractile ring constriction is driven by nonmuscle myosin II (NMII) translocation of antiparallel actin filaments. Here we report in situ, in vitro, and in vivo observations that challenge this hypothesis. Graded knockdown of NM II in cultured COS-7 cells reveals that the amount of NM II limits ring constriction. Restoration of the constriction rate with motor-impaired NM II mutants shows that the ability of NM II to translocate actin is not required for cytokinesis. Blebbistatin inhibition of cytokinesis indicates the importance of myosin strongly binding to actin and exerting tension during cytokinesis. This role is substantiated by transient kinetic experiments showing that the load-dependent mechanochemical properties of mutant NM II support efficient tension maintenance despite the inability to translocate actin. Under loaded conditions, mutant NM II exhibits a prolonged actin attachment in which a single mechanoenzymatic cycle spans most of the time of cytokinesis. This prolonged attachment promotes simultaneous binding of NM II heads to actin, thereby increasing tension and resisting expansion of the ring. The detachment of mutant NM II heads from actin is enhanced by assisting loads, which prevent mutant NM II from hampering furrow ingression during cytokinesis. In the 3D context of mouse hearts, mutant NM II-B R709C that cannot translocate actin filaments can rescue multinucleation in NM II-B ablated cardiomyocytes. We propose that the major roles of NM II in vertebrate cell cytokinesis are to bind and cross-link actin filaments and to exert tension on actin during contractile ring constriction.
C1 [Ma, Xuefei; Conti, Mary Anne; Wang, Aibing; Zhang, Yingfan; Adelstein, Robert S.] NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA.
   [Kovacs, Mihaly] Eotvos Lorand Univ, Hungarian Acad Sci, Momentum Motor Enzymol Res Grp, Dept Biochem, H-1117 Budapest, Hungary.
   [Sellers, James R.] NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA.
RP Adelstein, RS (reprint author), NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA.
EM adelster@nhlbi.nih.gov
RI Kovacs, Mihaly/A-6841-2011; 
OI Adelstein, Robert/0000-0002-8683-2144
FU Division of Intramural Research, National Heart, Lung, and Blood
   Institute; Norway Grant [NNF2-85613]; Hungarian Scientific Research Fund
   [K71915, NK81950]; Tarsadalmi Megujulas Operativ Program
   [4.2.1/B-09/1/KMR-2010-0003]; Hungarian Academy of Sciences
   [LP2011-006/2011]
FX We thank Dr. Dennis E. Discher (University of Pennsylvania) for
   providing the plasmid NMHC II-B Y277F; and Dr. Edward Korn (Laboratory
   of Cell Biology, National Heart, Lung, and Blood Institute), Dr. Sachiyo
   Kawamoto, and members of the Laboratory of Molecular Cardiology for
   critical comments on the manuscript. We also thank Dr. Douglas Robinson
   (The Johns Hopkins University School of Medicine) for his expertise in
   the analysis of the dynamics of cytokinesis; Dr. Jianjun Bao for help
   with COS-7 experiments; Drs. Chengyu Liu and Yubin Du (National Heart,
   Lung, and Blood Institute Transgenic Core); and Drs. Christian A. Combs
   and Daniela Malide (National Heart, Lung, and Blood Institute Light
   Microscopy Core) for professional skills and advice. Antoine Smith and
   Dalton Saunders provided excellent technical assistance. This research
   was supported by the Division of Intramural Research, National Heart,
   Lung, and Blood Institute. M. K. is a Bolyai Fellow of the Hungarian
   Academy of Sciences and is funded by Norway Grant NNF2-85613, the
   Hungarian Scientific Research Fund (K71915 and NK81950), Tarsadalmi
   Megujulas Operativ Program Grant 4.2.1/B-09/1/KMR-2010-0003, and the
   "Momentum" Program of the Hungarian Academy of Sciences
   (LP2011-006/2011).
NR 43
TC 52
Z9 52
U1 1
U2 10
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 20
PY 2012
VL 109
IS 12
BP 4509
EP 4514
DI 10.1073/pnas.1116268109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 911JH
UT WOS:000301712600037
PM 22393000
ER

PT J
AU Kumar, S
   Kellish, P
   Robinson, WE
   Wang, DY
   Appella, DH
   Arya, DP
AF Kumar, Sunil
   Kellish, Patrick
   Robinson, W. Edward, Jr.
   Wang, Deyun
   Appella, Daniel H.
   Arya, Dev P.
TI Click Dimers To Target HIV TAR RNA Conformation
SO BIOCHEMISTRY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; NUCLEIC ACID INTERACTIONS; LONG TERMINAL
   REPEAT; DNA TRIPLE-HELIX; B-DNA; NEOMYCIN CONJUGATE; MAJOR GROOVE;
   RECOGNITION; BINDING; PROTEIN
AB A series of neomycin dimers have been synthesized using "click chemistry" with varying functionality and length in the linker region to target the human immunodeficiency virus type 1 (HIV-1) TAR RNA region of the HIV virus. The TAR (Trans-Activation Responsive) RNA region, a 59 bp stem-loop structure located at the 5'-end of all nascent viral transcripts, interacts with its target, a key regulatory protein, Tat, and necessitates the replication of HIV-1. Neomycin, an aminosugar, has been shown to exhibit multiple binding sites on TAR RNA. This observation prompted us to design and synthesize a library of triazole-linked neomycin dimers using click chemistry. The binding between neomycin dimers and TAR RNA was characterized using spectroscopic techniques, including FID (fluorescent intercalator displacement), a FRET (fluorescence resonance energy transfer) competitive assay, circular dichroism (CD), and UV thermal denaturation. UV thermal denaturation studies demonstrate that binding of neomycin dimers increases the melting temperature (T-m) of the HIV TAR RNA up to 10 degrees C. Ethidium bromide displacement (FID) and a FRET competition assay revealed nanomolar binding affinity between neomycin dimers and HIV TAR RNA, while in case of neomycin, only weak binding was detected. More importantly, most of the dimers exhibited lower IC50 values toward HIV TAR RNA, when compared to the fluorescent Tat peptide, and show increased selectivity over mutant TAR RNA. Cytopathic effects investigated using MT-2 cells indicate a number of the dimers with high affinity toward TAR show promising anti-HIV activity.
C1 [Kumar, Sunil; Kellish, Patrick; Arya, Dev P.] Clemson Univ, Dept Chem, Med Chem Lab, Clemson, SC 29634 USA.
   [Robinson, W. Edward, Jr.] Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA 92697 USA.
   [Wang, Deyun; Appella, Daniel H.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Arya, DP (reprint author), Clemson Univ, Dept Chem, Med Chem Lab, Clemson, SC 29634 USA.
EM dparya@clemson.edu
RI perumal, murugiah/D-1565-2012
FU National Science Foundation [CHE/MCB-0134972]; National Institutes of
   Health [R15CA125724]
FX We thank the National Science Foundation (CHE/MCB-0134972) and the
   National Institutes of Health (R15CA125724) for financial support.
NR 67
TC 33
Z9 33
U1 4
U2 29
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD MAR 20
PY 2012
VL 51
IS 11
BP 2331
EP 2347
DI 10.1021/bi201657k
PG 17
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 910KX
UT WOS:000301636700017
PM 22339203
ER

PT J
AU Zhao, KJ
   Shi, YB
AF Zhao, Keji
   Shi, Yun-Bo
TI An anti-cancer Smurf
SO CELL AND BIOSCIENCE
LA English
DT Article
AB A novel, cancer-fighting function was recently discovered for Smad ubiquitination regulatory factor 2 (Smurf2).
C1 [Zhao, Keji] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
   [Shi, Yun-Bo] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Morphogenesis, PCRM, NIH, Bethesda, MD 20892 USA.
RP Zhao, KJ (reprint author), NHLBI, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM zhaok@nhlbi.nih.gov; shi@helix.nih.gov
FU Intramural Research Program of NHLBI, NIH; NICHD, NIH
FX The research in the authors' laboratories is supported by the Intramural
   Research Program of NHLBI (KZ) and NICHD (YBS), NIH.
NR 5
TC 1
Z9 1
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2045-3701
J9 CELL BIOSCI
JI Cell Biosci.
PD MAR 19
PY 2012
VL 2
AR 10
DI 10.1186/2045-3701-2-10
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 982RP
UT WOS:000307063400001
PM 22429979
ER

PT J
AU Ried, T
   Gaiser, T
AF Ried, Thomas
   Gaiser, Timo
TI A recurrent fusion gene in high-grade endometrial stromal sarcoma: a new
   tool for diagnosis and therapy?
SO GENOME MEDICINE
LA English
DT Editorial Material
ID CANCER
AB High-grade endometrial stromal sarcomas (ESSs) are an aggressive group of endometrial stromal tumors. A recent study described a recurrent chromosomal translocation (t(10;17)) occurring in ESS, which joins the gene 14-3-3 epsilon with either FAM22A or FAM22B. Expression of the resulting fusion gene leads to malignant transformation, and silencing of its expression reverses the malignant phenotype. Because the fusion can be readily detected in diagnostic samples using fluorescent in situ hybridization, this chromosomal aberration could be used to differentiate high-grade ESS from the low-grade, less aggressive form. Discovery of the new oncoprotein could also provide entry points for targeted therapies.
C1 [Ried, Thomas] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
   [Gaiser, Timo] Univ Med Mannheim, Dept Pathol, D-68167 Mannheim, Germany.
RP Ried, T (reprint author), NCI, Genet Branch, NIH, 50 South Dr, Bethesda, MD 20892 USA.
EM riedt@mail.nih.gov; timo.gaiser@umm.de
NR 11
TC 2
Z9 2
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-994X
J9 GENOME MED
JI Genome Med.
PD MAR 19
PY 2012
VL 4
AR 20
DI 10.1186/gm319
PG 3
WC Genetics & Heredity
SC Genetics & Heredity
GA 084VK
UT WOS:000314567100001
PM 22429906
ER

PT J
AU Baas, DC
   Ho, L
   Tanck, MWT
   Fritsche, LG
   Merriam, JE
   Van het Slot, R
   Koeleman, BPC
   Gorgels, TGMF
   van Duijn, CM
   Uitterlinden, AG
   de Jong, PTVM
   Hofman, A
   ten Brink, JB
   Vingerling, JR
   Klaver, CCW
   Dean, M
   Weber, BHF
   Allikmets, R
   Hageman, GS
   Bergen, AAB
AF Baas, Dominique C.
   Ho, Lintje
   Tanck, Michael W. T.
   Fritsche, Lars G.
   Merriam, Joanna E.
   Van het Slot, Ruben
   Koeleman, Bobby P. C.
   Gorgels, Theo G. M. F.
   van Duijn, Cornelia M.
   Uitterlinden, Andre G.
   de Jong, Paulus T. V. M.
   Hofman, Albert
   ten Brink, Jacoline B.
   Vingerling, Johannes R.
   Klaver, Caroline C. W.
   Dean, Michael
   Weber, Bernhard H. F.
   Allikmets, Rando
   Hageman, Gregory S.
   Bergen, Arthur A. B.
TI Multicenter cohort association study of SLC2A1 single nucleotide
   polymorphisms and age-related macular degeneration
SO MOLECULAR VISION
LA English
DT Article
ID DEPENDENT DIABETES-MELLITUS; TRANSPORTER GLUT1 GENE; COMPLEMENT
   FACTOR-H; BLOOD-BRAIN-BARRIER; GLUCOSE-TRANSPORTER; HUMAN EYE;
   ENDOTHELIAL-CELLS; SERPING1 GENE; UNITED-STATES; SUSCEPTIBILITY
AB Purpose: Age-related macular degeneration (AMD) is a major cause of blindness in older adults and has a genetically complex background. This study examines the potential association between single nucleotide polymorphisms (SNPs) in the glucose transporter 1 (SLC2A1) gene and AMD. SLC2A1 regulates the bioavailability of glucose in the retinal pigment epithelium (RPE), which might influence oxidative stress-mediated AMD pathology.
   Methods: Twenty-two SNPs spanning the SLC2A1 gene were genotyped in 375 cases and 199 controls from an initial discovery cohort (the Amsterdam-Rotterdam-Netherlands study). Replication testing was performed in The Rotterdam Study (the Netherlands) and study populations from Wurzburg (Germany), the Age Related Eye Disease Study (AREDS; United States), Columbia University (United States), and Iowa University (United States). Subsequently, a meta-analysis of SNP association was performed.
   Results: In the discovery cohort, significant genotypic association between three SNPs (rs3754219, rs4660687, and rs841853) and AMD was found. Replication in five large independent (Caucasian) cohorts (4,860 cases and 4,004 controls) did not yield consistent association results. The genotype frequencies for these SNPs were significantly different for the controls and/or cases among the six individual populations. Meta-analysis revealed significant heterogeneity of effect between the studies.
   Conclusions: No overall association between SLC2A1 SNPs and AMD was demonstrated. Since the genotype frequencies for the three SLC2A1 SNPs were significantly different for the controls and/or cases between the six cohorts, this study corroborates previous evidence that population dependent genetic risk heterogeneity in AMD exists.
C1 [Baas, Dominique C.; Gorgels, Theo G. M. F.; de Jong, Paulus T. V. M.; ten Brink, Jacoline B.; Bergen, Arthur A. B.] NIN, Dept Clin & Mol Ophthalmogenet, Amsterdam, Netherlands.
   [Ho, Lintje; van Duijn, Cornelia M.; Uitterlinden, Andre G.; de Jong, Paulus T. V. M.; Hofman, Albert; Vingerling, Johannes R.; Klaver, Caroline C. W.] EMC, Dept Epidemiol, Rotterdam, Netherlands.
   [Ho, Lintje; Vingerling, Johannes R.; Klaver, Caroline C. W.] EMC, Dept Ophthalmol, Rotterdam, Netherlands.
   [Tanck, Michael W. T.] AMC, Dept Clin Epidemiol Biostat & Bioinformat, Amsterdam, Netherlands.
   [Fritsche, Lars G.; Weber, Bernhard H. F.] Univ Regensburg, Inst Human Genet, Regensburg, Germany.
   [Merriam, Joanna E.; Allikmets, Rando] Columbia Univ, Dept Ophthalmol Pathol & Cell Biol, New York, NY USA.
   [Van het Slot, Ruben; Koeleman, Bobby P. C.] UMC, Dept Med Genet, Res Sect, Utrecht, Netherlands.
   [de Jong, Paulus T. V. M.; Bergen, Arthur A. B.] AMC, Dept Ophthalmol, Amsterdam, Netherlands.
   [Uitterlinden, Andre G.] EMC, Dept Internal Med, Rotterdam, Netherlands.
   [Dean, Michael] NCI, Lab Expt Immunol, Canc & Inflammat Program, Frederick, MD 21701 USA.
   [Hageman, Gregory S.] Univ Iowa, Dept Ophthalmol & Visual Sci, Iowa City, IA 52242 USA.
   [Hageman, Gregory S.] Univ Calif Santa Barbara, Ctr Study Macular Degenerat, Santa Barbara, CA 93106 USA.
   [Bergen, Arthur A. B.] AMC, Dept Clin Genet, Amsterdam, Netherlands.
RP Bergen, AAB (reprint author), Meibergdreef 47, NL-1105 BA Amsterdam, Netherlands.
EM a.bergen@nin.knaw.nl
RI Dean, Michael/G-8172-2012; Bergen, Arthur/J-3637-2013
OI Dean, Michael/0000-0003-2234-0631; 
FU Merck Sharpe and Dohme; Algemene Nederlandse Vereniging ter Voorkoming
   van Blindheid; Netherlands Macula Fund; LSBS; Netherlands Organization
   for Scientific Research (NWO) Investments [175.010.2005.011,
   911-03-012]; Research Institute for Diseases in the Elderly [014-93-015,
   RIDE2]; Netherlands Genomics Initiative (NGI)/NWO [050-060-810]; EMC and
   Erasmus University, Netherlands Organization for Health Research and
   Development (ZonMw); Ministries of Education, Culture and Science, and
   Health, Welfare and Sports; European Commission; Municipality of
   Rotterdam; National Cancer Institute, National Institutes of Health;
   National Eye Institute [EY13435, EY017404]; Macula Vision Research
   Foundation; Kaplen Foundation; Wigdeon Point Charitable Foundations;
   Research to Prevent Blindness; Department of Ophthalmology & Visual
   Sciences, University of Utah [NIHR24]; Research to Prevent Blindness,
   Inc. Baltimore, MD, USA
FX This study was in part financed by an unrestricted research grant from
   Merck Sharpe and Dohme and by the Algemene Nederlandse Vereniging ter
   Voorkoming van Blindheid, The Netherlands Macula Fund and LSBS (all to
   A.A.B). GWAS genotype data for the Rotterdam Study is supported by the
   Netherlands Organization for Scientific Research (NWO) Investments (nr.
   175.010.2005.011, 911-03-012). This study is funded by the Research
   Institute for Diseases in the Elderly (014-93-015; RIDE2), the
   Netherlands Genomics Initiative (NGI)/NWO project nr. 050-060-810, the
   EMC and Erasmus University, Netherlands Organization for Health Research
   and Development (ZonMw), the Ministries of Education, Culture and
   Science, and Health, Welfare and Sports, the European Commission, and
   the Municipality of Rotterdam. The Franconian AMD study would like to
   thank Claudia N. Keilhauer (Department of Ophthalmology, University of
   Wurzburg, Germany) for recruiting individuals with AMD and the control
   subjects. Kerstin Meier (Institute of Human Genetics, University of
   Regensburg, Germany) for technical assistance. AREDS was supported (in
   part) by the Intramural Research Program of the National Cancer
   Institute, National Institutes of Health. The Columbia University study
   is supported in part by the grants from the National Eye Institute
   EY13435 and EY017404; the Macula Vision Research Foundation; Kaplen
   Foundation; Wigdeon Point Charitable Foundations and an unrestricted
   grant from Research to Prevent Blindness. G.S.H is supported by an
   unrestricted NIHR24 grant to the Department of Ophthalmology & Visual
   Sciences, University of Utah and a Senior Scientist Award (GSH) from
   Research to Prevent Blindness, Inc. Baltimore, MD, USA. The University
   of Iowa would like to thank Chris Pappas for technical assistance.
NR 63
TC 3
Z9 3
U1 1
U2 6
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD MAR 17
PY 2012
VL 18
IS 72
BP 657
EP 674
PG 18
WC Biochemistry & Molecular Biology; Ophthalmology
SC Biochemistry & Molecular Biology; Ophthalmology
GA 947JC
UT WOS:000304425300001
PM 22509097
ER

PT J
AU Davey, G
   Bockarie, M
   Wanji, S
   Addiss, D
   Fuller, C
   Fox, L
   Mycoskie, M
   Gruin, M
   Tsegaye, A
   Ayele, FT
   Newport, M
AF Davey, Gail
   Bockarie, Moses
   Wanji, Samuel
   Addiss, David
   Fuller, Claire
   Fox, LeAnne
   Mycoskie, Mike
   Gruin, Mark
   Tsegaye, Aster
   Ayele, Fasil Tekola
   Newport, Melanie
TI Launch of the International Podoconiosis Initiative
SO LANCET
LA English
DT Letter
ID SOUTHERN ETHIOPIA
C1 [Davey, Gail; Newport, Melanie] Univ Sussex, Brighton & Sussex Med Sch, Brighton BN1 9PS, E Sussex, England.
   [Bockarie, Moses] Univ Liverpool, Liverpool Sch Trop Med, Liverpool L3 5QA, Merseyside, England.
   [Wanji, Samuel] Res Fdn Trop Dis & Environm, Buea, Cameroon.
   [Addiss, David] Children Worms, Decatur, GA USA.
   [Fuller, Claire] Int Fdn Dermatol, London, England.
   [Fox, LeAnne] Ctr Dis Control & Prevent, Atlanta, GA USA.
   [Mycoskie, Mike] TOMS Shoes Inc, Santa Monica, CA USA.
   [Gruin, Mark] Int Orthodox Christian Char, Baltimore, MD USA.
   [Tsegaye, Aster] Univ Addis Ababa, Addis Ababa, Ethiopia.
   [Ayele, Fasil Tekola] NIH, Bethesda, MD 20892 USA.
RP Davey, G (reprint author), Univ Sussex, Brighton & Sussex Med Sch, Brighton BN1 9PS, E Sussex, England.
EM g.davey@bsms.ac.uk
OI Davey, Gail/0000-0003-2796-7468
FU Medical Research Council [G1001337, MR/J008621/1]
NR 5
TC 6
Z9 6
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 MAR 17
PY 2012
VL 379
IS 9820
BP 1004
EP 1004
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 911JE
UT WOS:000301712300027
PM 22423883
ER

PT J
AU Thapar, A
   Collishaw, S
   Pine, DS
   Thapar, AK
AF Thapar, Anita
   Collishaw, Stephan
   Pine, Daniel S.
   Thapar, Ajay K.
TI Depression in adolescence
SO LANCET
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; COGNITIVE-BEHAVIORAL THERAPY; SEROTONIN
   TRANSPORTER GENE; MIDDLE-INCOME COUNTRIES; RECENT LIFE EVENTS; MAJOR
   DEPRESSION; MATERNAL DEPRESSION; MENTAL-HEALTH; PSYCHIATRIC-DISORDERS;
   COMMUNITY SAMPLE
AB Unipolar depressive disorder in adolescence is common worldwide but often unrecognised. The incidence, notably in girls, rises sharply after puberty and, by the end of adolescence, the 1 year prevalence rate exceeds 4%. The burden is highest in low-income and middle-income countries. Depression is associated with substantial present and future morbidity, and heightens suicide risk. The strongest risk factors for depression in adolescents are a family history of depression and exposure to psychosocial stress. Inherited risks, develop mental factors, sex hormones, and psychosocial adversity interact to increase risk through hormonal factors and associated perturbed neural pathways. Although many similarities between depression in adolescence and depression in adulthood exist, in adolescents the use of antidepressants is of concern and opinions about clinical management are divided. Effective treatments are available, but choices are dependent on depression severity and available resources. Prevention strategies targeted at high-risk groups are promising.
C1 [Thapar, Anita; Collishaw, Stephan; Thapar, Ajay K.] Cardiff Univ, Sch Med, Dept Psychol Med & Neurol, Child & Adolescent Psychiat Sect, Cardiff CF14 4XN, S Glam, Wales.
   [Thapar, Anita; Collishaw, Stephan] Cardiff Univ, Sch Med, MRC Ctr Neuropsychiat Genet & Genom, Cardiff CF14 4XN, S Glam, Wales.
   [Pine, Daniel S.] NIMH, Emot & Dev Branch, Intramural Res Program, Bethesda, MD 20892 USA.
   [Thapar, Ajay K.] Taff Riverside Practice, Cardiff, S Glam, Wales.
RP Thapar, A (reprint author), Cardiff Univ, Sch Med, Dept Psychol Med & Neurol, Child & Adolescent Psychiat Sect, Heath Pk, Cardiff CF14 4XN, S Glam, Wales.
EM thapar@Cardiff.ac.uk
OI Collishaw, Stephan/0000-0002-4296-820X; Thapar,
   Anita/0000-0002-3689-737X
FU Sir Jules Thorn Charitable Trust; Waterloo Foundation
FX The authors' research on depression is funded by the Sir Jules Thorn
   Charitable Trust. SC is supported by the Waterloo Foundation. We thank
   Sir Michael Rutter, Antonio Munoz, Robert Potter, Gemma Lewis, and
   Miriam Cooper for comments on an earlier draft, Robert Goodman for
   advice, and Peter MacSorley (medical student) for assistance with the
   literature search.
NR 152
TC 207
Z9 220
U1 21
U2 145
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 MAR 17
PY 2012
VL 379
IS 9820
BP 1056
EP 1067
DI 10.1016/S0140-6736(11)60871-4
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA 911JE
UT WOS:000301712300034
PM 22305766
ER

PT J
AU Chawla, B
   Kumar, RR
   Tyagi, N
   Subramanian, G
   Srinivasan, N
   Park, MH
   Madhubala, R
AF Chawla, Bhavna
   Kumar, Ravi Ranjan
   Tyagi, Nidhi
   Subramanian, Gowri
   Srinivasan, N.
   Park, Myung Hee
   Madhubala, Rentala
TI A Unique Modification of the Eukaryotic Initiation Factor 5A Shows the
   Presence of the Complete Hypusine Pathway in Leishmania donovani
SO PLOS ONE
LA English
DT Article
ID YEAST SACCHAROMYCES-CEREVISIAE; AMINO-ACID-RESIDUES; DEOXYHYPUSINE
   HYDROXYLASE; CELL-GROWTH; 3-DIMENSIONAL STRUCTURES; CONTAINING PROTEIN;
   IDENTIFICATION; SYNTHASE; SPERMIDINE; PRECURSOR
AB Deoxyhypusine hydroxylase (DOHH) catalyzes the final step in the post-translational synthesis of an unusual amino acid hypusine (N-(sic)-(4-amino-2-hydroxybutyl) lysine), which is present on only one cellular protein, eukaryotic initiation factor 5A (eIF5A). We present here the molecular and structural basis of the function of DOHH from the protozoan parasite, Leishmania donovani, which causes visceral leishmaniasis. The L. donovani DOHH gene is 981 bp and encodes a putative polypeptide of 326 amino acids. DOHH is a HEAT-repeat protein with eight tandem repeats of alpha-helical pairs. Four conserved histidine-glutamate sequences have been identified that may act as metal coordination sites. A similar to 42 kDa recombinant protein with a His-tag was obtained by heterologous expression of DOHH in Escherichia coli. Purified recombinant DOHH effectively catalyzed the hydroxylation of the intermediate, eIF5A-deoxyhypusine (eIF5A-Dhp), in vitro. L. donovani DOHH (LdDOHH) showed similar to 40.6% sequence identity with its human homolog. The alignment of L. donovani DOHH with the human homolog shows that there are two significant insertions in the former, corresponding to the alignment positions 159-162 (four amino acid residues) and 174-183 (ten amino acid residues) which are present in the variable loop connecting the N- and C-terminal halves of the protein, the latter being present near the substrate binding site. Deletion of the ten-amino-acid-long insertion decreased LdDOHH activity to 14% of the wild type recombinant LdDOHH. Metal chelators like ciclopirox olamine (CPX) and mimosine significantly inhibited the growth of L. donovani and DOHH activity in vitro. These inhibitors were more effective against the parasite enzyme than the human enzyme. This report, for the first time, confirms the presence of a complete hypusine pathway in a kinetoplastid unlike eubacteria and archaea. The structural differences between the L. donovani DOHH and the human homolog may be exploited for structure based design of selective inhibitors against the parasite.
C1 [Chawla, Bhavna; Kumar, Ravi Ranjan; Subramanian, Gowri; Madhubala, Rentala] Jawaharlal Nehru Univ, Sch Life Sci, New Delhi 110067, India.
   [Tyagi, Nidhi; Srinivasan, N.] Indian Inst Sci, Mol Biophys Unit, Bangalore 560012, Karnataka, India.
   [Park, Myung Hee] NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
RP Chawla, B (reprint author), Jawaharlal Nehru Univ, Sch Life Sci, New Delhi 110067, India.
EM madhubala@mail.jnu.ac.in
OI madhubala, rentala/0000-0002-0034-399X; Tyagi, Nidhi/0000-0002-2065-9051
FU Council of Scientific and Industrial Research (CSIR), India; Department
   of Science and Technology (DST), India
FX This work is supported by a grant from the Council of Scientific and
   Industrial Research (CSIR), India to Dr. Madhubala. Dr. Madhubala is a
   JC Bose Fellow supported by the Department of Science and Technology
   (DST), India. Dr. Chawla, Ravi Ranjan Kumar and Nidhi Tyagi are
   supported by CSIR, India. The funders had no role in study design, data
   collection and analysis, decision to publish, or preparation of the
   manuscript.
NR 44
TC 13
Z9 14
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 16
PY 2012
VL 7
IS 3
AR e33138
DI 10.1371/journal.pone.0033138
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 932RV
UT WOS:000303309100024
PM 22438895
ER

PT J
AU Sun, C
   Fang, H
   Xie, T
   Auth, RD
   Patel, N
   Murray, PR
   Snoy, PJ
   Frucht, DM
AF Sun, Chen
   Fang, Hui
   Xie, Tao
   Auth, Roger D.
   Patel, Nayana
   Murray, Patrick R.
   Snoy, Philip J.
   Frucht, David M.
TI Anthrax Lethal Toxin Disrupts Intestinal Barrier Function and Causes
   Systemic Infections with Enteric Bacteria
SO PLOS ONE
LA English
DT Article
ID BACILLUS-ANTHRACIS; KAPPA-B; CELLS; ACTIVATION
AB A variety of intestinal pathogens have virulence factors that target mitogen activated protein kinase (MAPK) signaling pathways, including Bacillus anthracis. Anthrax lethal toxin (LT) has specific proteolytic activity against the upstream regulators of MAPKs, the MAPK kinases (MKKs). Using a murine model of intoxication, we show that LT causes the dose-dependent disruption of intestinal epithelial integrity, characterized by mucosal erosion, ulceration, and bleeding. This pathology correlates with an LT-dependent blockade of intestinal crypt cell proliferation, accompanied by marked apoptosis in the villus tips. C57BL/6J mice treated with intravenous LT nearly uniformly develop systemic infections with commensal enteric organisms within 72 hours of administration. LT-dependent intestinal pathology depends upon its proteolytic activity and is partially attenuated by co-administration of broad spectrum antibiotics, indicating that it is both a cause and an effect of infection. These findings indicate that targeting of MAPK signaling pathways by anthrax LT compromises the structural integrity of the mucosal layer, serving to undermine the effectiveness of the intestinal barrier. Combined with the well-described immunosuppressive effects of LT, this disruption of the intestinal barrier provides a potential mechanism for host invasion via the enteric route, a common portal of entry during the natural infection cycle of Bacillus anthracis.
C1 [Sun, Chen; Fang, Hui; Xie, Tao; Auth, Roger D.; Frucht, David M.] US FDA, Cell Biol Lab, Div Monoclonal Antibodies, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA.
   [Patel, Nayana; Murray, Patrick R.] NIH, Dept Lab Med, Warren Magnusen Clin Ctr, Bethesda, MD 20892 USA.
   [Snoy, Philip J.] US FDA, Div Vet Serv, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
RP Sun, C (reprint author), US FDA, Cell Biol Lab, Div Monoclonal Antibodies, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA.
EM david.frucht@fda.hhs.gov
FU United States government
FX The United States government provided the funding to support this work.
   The information presented in this manuscript reflects the work of the
   authors and does not necessarily represent the policy of the United
   States Food and Drug Administration. The funders had no role in study
   design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
NR 33
TC 9
Z9 9
U1 0
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 MAR 16
PY 2012
VL 7
IS 3
AR e33583
DI 10.1371/journal.pone.0033583
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 932RV
UT WOS:000303309100061
PM 22438953
ER

PT J
AU Pazgier, M
   Wei, G
   Ericksen, B
   Jung, G
   Wu, ZB
   de Leeuw, E
   Yuan, WR
   Szmacinski, H
   Lu, WY
   Lubkowski, J
   Lehrer, RI
   Lu, WY
AF Pazgier, Marzena
   Wei, Gang
   Ericksen, Bryan
   Jung, Grace
   Wu, Zhibin
   de Leeuw, Erik
   Yuan, Weirong
   Szmacinski, Henryk
   Lu, Wei-Yue
   Lubkowski, Jacek
   Lehrer, Robert I.
   Lu, Wuyuan
TI Sometimes It Takes Two to Tango CONTRIBUTIONS OF DIMERIZATION TO
   FUNCTIONS OF HUMAN alpha-DEFENSIN HNP1 PEPTIDE
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HUMAN ALPHA-DEFENSINS; PRECURSOR LIPID II; ANTIMICROBIAL PEPTIDES;
   INNATE IMMUNITY; PANETH CELLS; MECHANISM; DIMER; PROTEIN; BINDING; HD5
AB Human myeloid alpha-defensins called HNPs play multiple roles in innate host defense. The Trp-26 residue of HNP1 was previously shown to contribute importantly to its ability to kill S. aureus, inhibit anthrax lethal factor (LF), bind gp120 of HIV-1, dimerize, and undergo further self-association. To gain additional insights into the functional significance of dimerization, we compared wild type HNP1 to dimerization-impaired, N-methylated HNP1 monomers and to disulfide-tethered obligate HNP1 dimers. The structural effects of these modifications were confirmed by x-ray crystallographic analyses. Like the previously studied W26A mutation, N-methylation of Ile-20 dramatically reduced the ability of HNP1 to kill Staphylococcus aureus, inhibit LF, and bind gp120. Importantly, this modification had minimal effect on the ability of HNP1 to kill Escherichia coli. The W26A and MeIle-20 mutations impaired defensin activity synergistically. N-terminal covalent tethering rescued the ability of W26A-HNP1 to inhibit LF but failed to restore its defective killing of S. aureus. Surface plasmon resonance studies revealed that Trp-26 mediated the association of monomers and canonical dimers of HNP1 to immobilized HNP1, LF, and gp120, and also indicated a possible mode of tetramerization of HNP1 mediated by Ile-20 and Leu-25. This study demonstrates that dimerization contributes to some but not all of the many and varied activities of HNP1.
C1 [Pazgier, Marzena; Lubkowski, Jacek] NCI, Macromol Assembly Struct & Cell Signaling Sect, NIH, Frederick, MD 21702 USA.
   [Pazgier, Marzena; Wei, Gang; Ericksen, Bryan; Wu, Zhibin; de Leeuw, Erik; Yuan, Weirong; Lu, Wuyuan] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA.
   [Szmacinski, Henryk; Lu, Wuyuan] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA.
   [Wei, Gang; Lu, Wei-Yue] Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China.
   [Jung, Grace; Lehrer, Robert I.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
RP Lubkowski, J (reprint author), NCI, Macromol Assembly Struct & Cell Signaling Sect, NIH, Frederick, MD 21702 USA.
EM lubkowsj@mail.nih.gov; wlu@ihv.umaryland.edu
RI Lu, Wuyuan/B-2268-2010; Ericksen, Bryan/F-9047-2012; Lu,
   Weiyue/E-7938-2010
FU United States Department of Energy, Office of Science [W-31-109-Eng38];
   United States Department of Energy, Office of Basic Energy Sciences
   [W-31-109-Eng38]; National Institutes of Health [AI072732, AI061482];
   NCI, Center for Cancer Research; National Natural Science Foundation of
   China [30701060]
FX We thank the X-ray Crystallography Core Facility of the University of
   Maryland at Baltimore for providing crystallographic equipment and
   resources. Use of the Advanced Photon Source was supported by the United
   States Department of Energy, Offices of Science and of Basic Energy
   Sciences, under Contract W-31-109-Eng38.; This work was supported, in
   whole or in part, by National Institutes of Health Grants AI072732 and
   AI061482 (to W. L.) and by the Intramural Research Program, NCI, Center
   for Cancer Research (to J. L.).; Supported by National Natural Science
   Foundation of China Grant 30701060.
NR 52
TC 22
Z9 22
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 MAR 16
PY 2012
VL 287
IS 12
BP 8944
EP 8953
DI 10.1074/jbc.M111.332205
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 912KV
UT WOS:000301797800025
PM 22270360
ER

PT J
AU Kasiviswanathan, R
   Gustafson, MA
   Copeland, WC
   Meyer, JN
AF Kasiviswanathan, Rajesh
   Gustafson, Margaret A.
   Copeland, William C.
   Meyer, Joel N.
TI Human Mitochondrial DNA Polymerase gamma Exhibits Potential for Bypass
   and Mutagenesis at UV-induced Cyclobutane Thymine Dimers
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ULTRAVIOLET-RADIATION EXPOSURE; MISMATCH-REPAIR ACTIVITY; NONMELANOMA
   SKIN-CANCER; ESCHERICHIA-COLI; NUCLEOTIDE INCORPORATION; MAMMALIAN
   MITOCHONDRIA; MALIGNANT-MELANOMA; OXIDATIVE STRESS; COMMON DELETION;
   LESION BYPASS
AB Cyclobutane thymine dimers (T-T) comprise the majority of DNA damage caused by short wavelength ultraviolet radiation. These lesions generally block replicative DNA polymerases and are repaired by nucleotide excision repair or bypassed by translesion polymerases in the nucleus. Mitochondria lack nucleotide excision repair, and therefore, it is important to understand how the sole mitochondrial DNA polymerase, pol gamma, interacts with irreparable lesions such as T-T. We performed in vitro DNA polymerization assays to measure the kinetics of incorporation opposite the lesion and bypass of the lesion by pol gamma with a dimer-containing template. Exonuclease-deficient pol gamma bypassed thymine dimers with low relative efficiency; bypass was attenuated but still detectable when using exonuclease-proficient pol gamma. When bypass did occur, pol gamma misincorporated a guanine residue opposite the 3'-thymine of the dimer only 4-fold less efficiently than it incorporated an adenine. Surprisingly, the pol gamma exonuclease-proficient enzyme excised the incorrectly incorporated guanine at similar rates irrespective of the nature of the thymines in the template. In the presence of all four dNTPs, pol gamma extended the primer after incorporation of two adenines opposite the lesion with relatively higher efficiency compared with extension past either an adenine or a guanine incorporated opposite the 3'-thymine of the T-T. Our results suggest that T-T usually stalls mitochondrial DNA replication but also suggest a mechanism for the introduction of point mutations and deletions in the mitochondrial genomes of chronically UV-exposed cells.
C1 [Gustafson, Margaret A.; Meyer, Joel N.] Duke Univ, Nicholas Sch Environm, Durham, NC 27708 USA.
   [Kasiviswanathan, Rajesh; Copeland, William C.] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Meyer, JN (reprint author), Duke Univ, Nicholas Sch Environm, Durham, NC 27708 USA.
EM joel.meyer@duke.edu
RI Kasiviswanathan, Rajesh/D-2744-2012
FU National Institutes of Health [R21 NS065468, ES 065078]
FX This work was supported, in whole or in part, by National Institutes of
   Health Grant R21 NS065468 (to J. N. M.) and ES 065078 (to W. C. C.).
NR 59
TC 18
Z9 19
U1 0
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAR 16
PY 2012
VL 287
IS 12
BP 9222
EP 9229
DI 10.1074/jbc.M111.306852
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 912KV
UT WOS:000301797800050
PM 22194617
ER

PT J
AU Zhang, YH
   Li, ZG
   Sacks, DB
   Ames, JB
AF Zhang, Yonghong
   Li, Zhigang
   Sacks, David B.
   Ames, James B.
TI Structural Basis for Ca2+-induced Activation and Dimerization of
   Estrogen Receptor alpha by Calmodulin
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID TARGET RECOGNITION; BREAST-CANCER; TRANSCRIPTIONAL ACTIVITY;
   LIGHT-SCATTERING; CALCIUM-BINDING; NMR; COMPLEX; CHROMATOGRAPHY;
   CA2+/CALMODULIN; CONFORMATION
AB The estrogen receptor alpha (ER-alpha) regulates expression of target genes implicated in development, metabolism, and breast cancer. Calcium-dependent regulation of ER-alpha is critical for activating gene expression and is controlled by calmodulin (CaM). Here, we present the NMR structures for the two lobes of CaM each bound to a localized region of ER-alpha (residues 287-305). A model of the complete CaM alpha ER-alpha complex was constructed by combining these two structures with additional data. The two lobes of CaM both compete for binding at the same site on ER-alpha (residues 292, 296, 299, 302, and 303), which explains why full-length CaM binds two molecules of ER-alpha in a 1:2 complex and stabilizes ER-alpha dimerization. Exposed glutamate residues in CaM (Glu(11), Glu(14), Glu(84), and Glu(87)) form salt bridges with key lysine residues in ER-alpha (Lys(299), Lys(302), and Lys(303)), which are likely to prevent ubiquitination at these sites and inhibit degradation of ER-alpha. Mutants of ER-alpha at the CaM-binding site (W292A and K299A) weaken binding to CaM, and I298E/K299D disrupts estrogen-induced transcription. CaM facilitates dimerization of ER-alpha in the absence of estrogen, and stimulation of ER-alpha by either Ca2+ and/or estrogen may serve to regulate transcription in a combinatorial fashion.
C1 [Zhang, Yonghong; Ames, James B.] Univ Calif Davis, Dept Chem, Davis, CA 95616 USA.
   [Li, Zhigang; Sacks, David B.] NIH, Dept Lab Med, Bethesda, MD 20892 USA.
RP Ames, JB (reprint author), Univ Calif Davis, Dept Chem, 1 Shields Ave, Davis, CA 95616 USA.
EM ames@chem.ucdavis.edu
FU National Institutes of Health [EY012347, NS059969]; Intramural Research
   Program
FX This work was supported, in whole or in part, by National Institutes of
   Health Grants EY012347 and NS059969 (to J. B. A.) and by the Intramural
   Research Program.
NR 57
TC 15
Z9 15
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 MAR 16
PY 2012
VL 287
IS 12
BP 9336
EP 9344
DI 10.1074/jbc.M111.334797
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 912KV
UT WOS:000301797800065
PM 22275375
ER

PT J
AU Chen, CY
   Samuel, TK
   Krause, M
   Dailey, HA
   Hamza, I
AF Chen, Caiyong
   Samuel, Tamika K.
   Krause, Michael
   Dailey, Harry A.
   Hamza, Iqbal
TI Heme Utilization in the Caenorhabditis elegans Hypodermal Cells Is
   Facilitated by Heme-responsive Gene-2
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID GLUTATHIONE-S-TRANSFERASE; BINDING PROTEIN; MOLECULAR CHARACTERIZATION;
   SACCHAROMYCES-CEREVISIAE; CADMIUM TOXICITY; CYTOCHROME-C; IRON UPTAKE;
   IDENTIFICATION; TRANSPORT; REDOX
AB The roundworm Caenorhabditis elegans is a heme auxotroph that requires the coordinated actions of HRG-1 heme permeases to transport environmental heme into the intestine and HRG-3, a secreted protein, to deliver intestinal heme to other tissues including the embryo. Here we show that heme homeostasis in the extraintestinal hypodermal tissue was facilitated by the transmembrane protein HRG-2. Systemic heme deficiency up-regulated hrg-2 mRNA expression over 200-fold in the main body hypodermal syncytium, hyp 7. HRG-2 is a type I membrane protein that binds heme and localizes to the endoplasmic reticulum and apical plasma membrane. Cytochrome heme profiles are aberrant in HRG-2-deficient worms, a phenotype that was partially suppressed by heme supplementation. A heme-deficient yeast strain, ectopically expressing worm HRG-2, revealed significantly improved growth at submicromolar concentrations of exogenous heme. Taken together, our results implicate HRG-2 as a facilitator of heme utilization in the Caenorhabditis elegans hypodermis and provide a mechanism for the regulation of heme homeostasis in an extraintestinal tissue.
C1 [Chen, Caiyong; Samuel, Tamika K.; Hamza, Iqbal] Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA.
   [Chen, Caiyong; Samuel, Tamika K.; Hamza, Iqbal] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA.
   [Krause, Michael] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
   [Dailey, Harry A.] Univ Georgia, Dept Microbiol, Biomed & Hlth Sci Inst, Athens, GA 30602 USA.
   [Dailey, Harry A.] Univ Georgia, Dept Biochem & Mol Biol, Biomed & Hlth Sci Inst, Athens, GA 30602 USA.
RP Hamza, I (reprint author), Univ Maryland, Dept Anim & Avian Sci, 2413 ANSC,Bldg 142, College Pk, MD 20742 USA.
EM hamza@umd.edu
OI Krause, Michael/0000-0001-6127-3940
FU National Institutes of Health (NIH) [R01DK74797]; NIH from NIDDK
FX This work was supported, in whole or in part, by National Institutes of
   Health (NIH) Grant R01DK74797 (extramural funding) (to I. H.) and an NIH
   Intramural Research Program grant from the NIDDK (to M. K.).
NR 59
TC 14
Z9 18
U1 1
U2 8
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 MAR 16
PY 2012
VL 287
IS 12
BP 9601
EP 9612
DI 10.1074/jbc.M111.307694
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 912KV
UT WOS:000301797800091
PM 22303006
ER

PT J
AU Inagaki, S
   Ghirlando, R
   White, JF
   Gvozdenovic-Jeremic, J
   Northup, JK
   Grisshammer, R
AF Inagaki, Sayaka
   Ghirlando, Rodolfo
   White, Jim F.
   Gvozdenovic-Jeremic, Jelena
   Northup, John K.
   Grisshammer, Reinhard
TI Modulation of the Interaction between Neurotensin Receptor NTS1 and Gq
   Protein by Lipid
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE G-protein-coupled receptor; G protein; nanodisc; lipid; charge
ID PHOSPHOLIPID-BILAYER NANODISCS; GTP-BINDING PROTEIN; COUPLED RECEPTORS;
   MONOMERIC RHODOPSIN; ANALYTICAL ULTRACENTRIFUGATION; FUNCTIONAL
   RECONSTITUTION; VISUAL TRANSDUCTION; MEMBRANE-PROTEINS;
   METARHODOPSIN-II; ROLES
AB Membrane lipids have been implicated to influence the activity of G-protein-coupled receptors (GPCRs). Almost all of our knowledge on the role of lipids on GPCR and G protein function comes from work on the visual pigment rhodopsin and its G protein transducin, which reside in a highly specialized membrane environment. Thus, insight gained from rhodopsin signaling may not be simply translated to other nonvisual GPCRs. Here, we investigated the effect of lipid head group charges on the signal transduction properties of the class A GPCR neurotensin (NT) receptor 1 (NTS1) under defined experimental conditions, using self-assembled phospholipid nanodiscs prepared with the zwitter-ionic lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), the negatively charged 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (POPG), or a POPC/POPG mixture. A combination of dynamic light scattering and sedimentation velocity showed that NTS1 was monomeric in POPC-, POPC/POPG-, and POPG-nanodiscs. Binding of the agonist NT to NTS1 occurred with similar affinities and was essentially unaffected by the phospholipid composition. In contrast, Gq protein coupling to NTS1 in various lipid nanodiscs was significantly different, and the apparent affinity of G alpha q and G beta(1)gamma(1) to activated NTS1 increased with increasing POPG content. NTS1-catalyzed GDP/GTP gamma S nucleotide exchange at G alpha q in the presence of G beta(1)gamma(1) and NT was crucially affected by the lipid type, with exchange rates higher by 1 or 2 orders of magnitude in POPC/POPG- and POPG-nanodiscs, respectively, compared to POPC-nanodiscs. Our data demonstrate that negatively charged lipids in the immediate vicinity of a nonvisual GPCR modulate the G-protein-coupling step. Published by Elsevier Ltd.
C1 [Inagaki, Sayaka; White, Jim F.; Gvozdenovic-Jeremic, Jelena; Grisshammer, Reinhard] NINDS, Membrane Prot Struct Funct Unit, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA.
   [Ghirlando, Rodolfo] NIDDKD, Mol Biol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
   [Northup, John K.] Natl Inst Deafness & Other Commun Disorders, Lab Cellular Biol, NIH, Dept Hlth & Human Serv, Rockville, MD 20850 USA.
RP Grisshammer, R (reprint author), NINDS, Membrane Prot Struct Funct Unit, NIH, Dept Hlth & Human Serv, 5625 Fishers Lane,Room 4S12, Rockville, MD 20852 USA.
EM rkgriss@helix.nih.gov
RI Grisshammer, Reinhard/C-3089-2015
FU National Institutes of Health
FX N-terminal protein sequence analysis was done at the Center for
   Biologics Evaluation and Research (Food and Drug Administration). DNA
   sequence analysis was performed by the National Institute of
   Neurological Disorders and Stroke (NINTDS) DNA Sequencing Facility. We
   thank Klaus Gawrisch and Walter Teague (National Institute on Alcohol
   Abuse and Alcoholism) for access to the NMR facility and for help and
   David Sibley (NINDS), Jurgen Wess (National Institute of Diabetes and
   Digestive and Kidney Diseases), Klaus Gawrisch (National Institute on
   Alcohol Abuse and Alcoholism), and Paul Randazzo (National Cancer
   Institute) for critical comments. This research was supported by the
   Intramural Research Program of the National Institutes of Health (S.I.,
   J.F.W., J.J., R. Grisshammer: NINDS; R. Ghirlando: National Institute of
   Diabetes and Digestive and Kidney Diseases; J.K.N.: National Institute
   on Deafness and Other Communication Disorders).
NR 99
TC 48
Z9 48
U1 2
U2 19
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 MAR 16
PY 2012
VL 417
IS 1-2
BP 95
EP 111
DI 10.1016/j.jmb.2012.01.023
PG 17
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 910XW
UT WOS:000301682900008
PM 22306739
ER

PT J
AU Stroncek, DF
   Berger, C
   Cheever, MA
   Childs, RW
   Dudley, ME
   Flynn, P
   Gattinoni, L
   Heath, JR
   Kalos, M
   Marincola, FM
   Miller, JS
   Mostoslavsky, G
   Powell, DJ
   Rao, M
   Restifo, NP
   Rosenberg, SA
   O'Shea, J
   Melief, CJM
AF Stroncek, David F.
   Berger, Carolina
   Cheever, Martin A.
   Childs, Richard W.
   Dudley, Mark E.
   Flynn, Peter
   Gattinoni, Luca
   Heath, James R.
   Kalos, Michael
   Marincola, Francesco M.
   Miller, Jeffrey S.
   Mostoslavsky, Gustavo
   Powell, Daniel J., Jr.
   Rao, Mahendra
   Restifo, Nicholas P.
   Rosenberg, Steven A.
   O'Shea, John
   Melief, Cornelis J. M.
TI New directions in cellular therapy of cancer: a summary of the summit on
   cellular therapy for cancer
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
ID PLURIPOTENT STEM-CELLS; TUMOR-INFILTRATING LYMPHOCYTES; ENGINEERED
   T-CELLS; ADOPTIVE TRANSFER; METASTATIC MELANOMA; MEMORY; IMMUNOTHERAPY;
   REGRESSION; GENERATION; NUMBERS
AB A summit on cellular therapy for cancer discussed and presented advances related to the use of adoptive cellular therapy for melanoma and other cancers. The summit revealed that this field is advancing rapidly. Conventional cellular therapies, such as tumor infiltrating lymphocytes (TIL), are becoming more effective and more available. Gene therapy is becoming an important tool in adoptive cell therapy. Lymphocytes are being engineered to express high affinity T cell receptors (TCRs), chimeric antibody-T cell receptors (CARs) and cytokines. T cell subsets with more naive and stem cell-like characteristics have been shown in pre-clinical models to be more effective than unselected populations and it is now possible to reprogram T cells and to produce T cells with stem cell characteristics. In the future, combinations of adoptive transfer of T cells and specific vaccination against the cognate antigen can be envisaged to further enhance the effectiveness of these therapies.
C1 [Stroncek, David F.; Marincola, Francesco M.] NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA.
   [Berger, Carolina; Cheever, Martin A.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
   [Cheever, Martin A.] Canc Immunotherapy Trials Network CITN, Seattle, WA USA.
   [Childs, Richard W.] NHLBI, NIH, Bethesda, MD 20892 USA.
   [Dudley, Mark E.; Gattinoni, Luca; Restifo, Nicholas P.; Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
   [Flynn, Peter] Fate Therapeut Inc, San Diego, CA USA.
   [Heath, James R.] CALTECH, Pasadena, CA 91125 USA.
   [Kalos, Michael; Powell, Daniel J., Jr.] Univ Penn, Philadelphia, PA 19104 USA.
   [Marincola, Francesco M.] Ctr Human Immunol, NIH, Bethesda, MD USA.
   [Miller, Jeffrey S.] Univ Minnesota, Minneapolis, MN USA.
   [Mostoslavsky, Gustavo] Boston Univ, Sch Med, Boston, MA 02118 USA.
   [Rao, Mahendra] Ctr Regenerat Med, NIH, Bethesda, MD USA.
   [O'Shea, John] NIAMSD, Bethesda, MD 20892 USA.
   [Melief, Cornelis J. M.] Leiden Univ, Med Ctr, Leiden, Netherlands.
   [Melief, Cornelis J. M.] Immune Syst Activat, Leiden, Netherlands.
RP Stroncek, DF (reprint author), NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA.
EM dstroncek@cc.nih.gov
RI Gattinoni, Luca/A-2281-2008; Restifo, Nicholas/A-5713-2008; 
OI Gattinoni, Luca/0000-0003-2239-3282; Miller, Jeffrey
   S/0000-0002-0339-4944; Restifo, Nicholas P./0000-0003-4229-4580
NR 31
TC 24
Z9 25
U1 1
U2 16
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 MAR 15
PY 2012
VL 10
AR 48
DI 10.1186/1479-5876-10-48
PG 5
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 949CP
UT WOS:000304553800001
PM 22420641
ER

PT J
AU Castellano, JF
   Fletcher, BR
   Kelley-Bell, B
   Kim, DH
   Gallagher, M
   Rapp, PR
AF Castellano, James F.
   Fletcher, Bonnie R.
   Kelley-Bell, Bennett
   Kim, David H.
   Gallagher, Michela
   Rapp, Peter R.
TI Age-Related Memory Impairment Is Associated with Disrupted Multivariate
   Epigenetic Coordination in the Hippocampus
SO PLOS ONE
LA English
DT Article
ID SPATIAL-LEARNING IMPAIRMENT; GYRUS GRANULE NEURONS; LONG-TERM-MEMORY;
   SYNAPTIC PLASTICITY; TRANSCRIPTIONAL ACTIVATION; HISTONE ACETYLATION;
   RAT HIPPOCAMPUS; PHOSPHORYLATION; INHIBITORS; INDUCTION
AB Mounting evidence linking epigenetic regulation to memory-related synaptic plasticity raises the possibility that altered chromatin modification dynamics might contribute to age-dependent cognitive decline. Here we show that the coordinated orchestration of both baseline and experience-dependent epigenetic regulation seen in the young adult hippocampus is lost in association with cognitive aging. Using a well-characterized rat model that reliably distinguishes aged individuals with significant memory impairment from others with normal memory, no single epigenetic mark or experience-dependent modification in the hippocampus uniquely predicted differences in the cognitive outcome of aging. The results instead point to a multivariate pattern in which modification-specific, bidirectional chromatin regulation is dependent on recent behavioral experience, chronological age, cognitive status, and hippocampal region. Whereas many epigenetic signatures were coupled with memory capacity among young adults and aged rats with preserved cognitive function, such associations were absent among aged rats with deficits in hippocampal memory. By comparison with the emphasis in current preclinical translational research on promoting chromatin modifications permissive for gene expression, our findings suggest that optimally successful hippocampal aging may hinge instead on enabling coordinated control across the epigenetic landscape.
C1 [Castellano, James F.; Fletcher, Bonnie R.; Kelley-Bell, Bennett; Kim, David H.; Rapp, Peter R.] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA.
   [Castellano, James F.] Mt Sinai Sch Med, Grad Program Neurosci, New York, NY USA.
   [Gallagher, Michela] Johns Hopkins Univ, Dept Psychol & Brain Sci, Baltimore, MD USA.
RP Castellano, JF (reprint author), NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA.
EM rappp@mail.nih.gov
FU National Institute on Aging; National Institutes of Health [AG09973,
   AG032845]
FX This research was supported in part by the Intramural Research Program
   of the National Institute on Aging, and by National Institutes of Health
   grants AG09973 (MG) and AG032845 (JFC). The funders had no role in study
   design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
NR 45
TC 25
Z9 26
U1 1
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 MAR 15
PY 2012
VL 7
IS 3
AR e33249
DI 10.1371/journal.pone.0033249
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 932RU
UT WOS:000303309000016
PM 22438904
ER

PT J
AU Furl, N
   Gallagher, S
   Averbeck, BB
AF Furl, Nicholas
   Gallagher, Shannon
   Averbeck, Bruno B.
TI A Selective Emotional Decision-Making Bias Elicited by Facial
   Expressions
SO PLOS ONE
LA English
DT Article
ID PREDICTION ERRORS; TEMPORAL PREDICTION; HUMAN STRIATUM; LEARNING-TASK;
   NEURAL BASIS; HUMAN BRAIN; OXYTOCIN; REWARD; METAANALYSIS; PERCEPTION
AB Emotional and social information can sway otherwise rational decisions. For example, when participants decide between two faces that are probabilistically rewarded, they make biased choices that favor smiling relative to angry faces. This bias may arise because facial expressions evoke positive and negative emotional responses, which in turn may motivate social approach and avoidance. We tested a wide range of pictures that evoke emotions or convey social information, including animals, words, foods, a variety of scenes, and faces differing in trustworthiness or attractiveness, but we found only facial expressions biased decisions. Our results extend brain imaging and pharmacological findings, which suggest that a brain mechanism supporting social interaction may be involved. Facial expressions appear to exert special influence over this social interaction mechanism, one capable of biasing otherwise rational choices. These results illustrate that only specific types of emotional experiences can best sway our choices.
C1 [Furl, Nicholas; Gallagher, Shannon; Averbeck, Bruno B.] NIMH, Unit Learning & Decis Making, Neuropsychol Lab, Bethesda, MD 20892 USA.
RP Furl, N (reprint author), NIMH, Unit Learning & Decis Making, Neuropsychol Lab, Bethesda, MD 20892 USA.
EM nick.furl@mrc-cbu.cam.ac.uk
OI furl, nicholas/0000-0003-2488-1343
FU National Institutes of Health, National Institute of Mental Health
FX This work was supported by the Intramural Research Program of the
   National Institutes of Health, National Institute of Mental Health. The
   funders had no role in study design, data collection and analysis,
   decision to publish, or preparation of the manuscript.
NR 30
TC 10
Z9 10
U1 0
U2 17
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 MAR 15
PY 2012
VL 7
IS 3
AR e33461
DI 10.1371/journal.pone.0033461
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 932RU
UT WOS:000303309000027
PM 22438936
ER

PT J
AU Koch, BJ
   Ryan, JF
   Baxevanis, AD
AF Koch, Bernard J.
   Ryan, Joseph F.
   Baxevanis, Andreas D.
TI The Diversification of the LIM Superclass at the Base of the Metazoa
   Increased Subcellular Complexity and Promoted Multicellular
   Specialization
SO PLOS ONE
LA English
DT Article
ID CAENORHABDITIS-ELEGANS MUSCLE; FOCAL ADHESION PROTEIN; DOMAIN PROTEINS;
   ACTIN-BINDING; PLANAR POLARITY; HOMEOBOX GENES; CELL-ADHESION;
   ALPHA-ACTININ; F-ACTIN; GENOME
AB Background: Throughout evolution, the LIM domain has been deployed in many different domain configurations, which has led to the formation of a large and distinct group of proteins. LIM proteins are involved in relaying stimuli received at the cell surface to the nucleus in order to regulate cell structure, motility, and division. Despite their fundamental roles in cellular processes and human disease, little is known about the evolution of the LIM superclass.
   Results: We have identified and characterized all known LIM domain-containing proteins in six metazoans and three non-metazoans. In addition, we performed a phylogenetic analysis on all LIM domains and, in the process, have identified a number of novel non-LIM domains and motifs in each of these proteins. Based on these results, we have formalized a classification system for LIM proteins, provided reasonable timing for class and family origin events; and identified lineage-specific loss events. Our analysis is the first detailed description of the full set of LIM proteins from the non-bilaterian species examined in this study.
   Conclusion: Six of the 14 LIM classes originated in the stem lineage of the Metazoa. The expansion of the LIM superclass at the base of the Metazoa undoubtedly contributed to the increase in subcellular complexity required for the transition from a unicellular to multicellular lifestyle and, as such, was a critically important event in the history of animal multicellularity.
C1 [Koch, Bernard J.; Ryan, Joseph F.; Baxevanis, Andreas D.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
RP Koch, BJ (reprint author), NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
EM andy@nhgri.nih.gov
FU National Human Genome Research Institute, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
   National Human Genome Research Institute, National Institutes of Health.
   All authors work at the National Human Genome Research Institute,
   National Institutes of Health. The funders had no role in study design,
   data collection and analysis, decision to publish, or preparation of the
   manuscript.
NR 109
TC 13
Z9 13
U1 0
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 MAR 15
PY 2012
VL 7
IS 3
AR e33261
DI 10.1371/journal.pone.0033261
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 932RU
UT WOS:000303309000018
PM 22438907
ER

PT J
AU Shivalkar, M
   Giniger, E
AF Shivalkar, Madhuri
   Giniger, Edward
TI Control of Dendritic Morphogenesis by Trio in Drosophila melanogaster
SO PLOS ONE
LA English
DT Article
ID ABL TYROSINE KINASE; SENSORY NEURONS; AXON GROWTH; RAC GTPASES; GEF
   TRIO; MECHANISMS; GUIDANCE; ABELSON; PROTEIN; DOMAIN
AB Abl tyrosine kinase and its effectors among the Rho family of GTPases each act to control dendritic morphogenesis in Drosophila. It has not been established, however, which of the many GTPase regulators in the cell link these signaling molecules in the dendrite. In axons, the bifunctional guanine exchange factor, Trio, is an essential link between the Abl tyrosine kinase signaling pathway and Rho GTPases, particularly Rac, allowing these systems to act coordinately to control actin organization. In dendritic morphogenesis, however, Abl and Rac have contrary rather than reinforcing effects, raising the question of whether Trio is involved, and if so, whether it acts through Rac, Rho or both. We now find that Trio is expressed in sensory neurons of the Drosophila embryo and regulates their dendritic arborization. trio mutants display a reduction in dendritic branching and increase in average branch length, whereas over-expression of trio has the opposite effect. We further show that it is the Rac GEF domain of Trio, and not its Rho GEF domain that is primarily responsible for the dendritic function of Trio. Thus, Trio shapes the complexity of dendritic arbors and does so in a way that mimics the effects of its target, Rac.
C1 [Shivalkar, Madhuri; Giniger, Edward] Natl Inst Neurol Disorders & Stroke, Axon Guidance & Neural Connect Unit, Basic Neurosci Program, NIH, Bethesda, MD 20892 USA.
RP Shivalkar, M (reprint author), Natl Inst Neurol Disorders & Stroke, Axon Guidance & Neural Connect Unit, Basic Neurosci Program, NIH, Bethesda, MD 20892 USA.
EM ginigere@ninds.nih.gov
RI Giniger, Edward/C-1764-2015
OI Giniger, Edward/0000-0002-8340-6158
FU NINDS, NIH [Z01 NS003013]
FX This work was supported by the Intramural Research Program of the NINDS,
   NIH (Z01 NS003013). The funder had no role in study design, data
   collection and analysis, decision to publish, or preparation of the
   manuscript.
NR 38
TC 6
Z9 6
U1 0
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 MAR 15
PY 2012
VL 7
IS 3
AR e33737
DI 10.1371/journal.pone.0033737
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 932RU
UT WOS:000303309000037
PM 22438988
ER

PT J
AU Strokappe, N
   Szynol, A
   Aasa-Chapman, M
   Gorlani, A
   Quigley, AF
   Hulsik, DL
   Chen, L
   Weiss, R
   de Haard, H
   Verrips, T
AF Strokappe, Nika
   Szynol, Agnieszka
   Aasa-Chapman, Marlen
   Gorlani, Andrea
   Quigley, Anna Forsman
   Hulsik, David Lutje
   Chen, Lei
   Weiss, Robin
   de Haard, Hans
   Verrips, Theo
TI Llama Antibody Fragments Recognizing Various Epitopes of the CD4bs
   Neutralize a Broad Range of HIV-1 Subtypes A, B and C
SO PLOS ONE
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODIES; GP120
   ENVELOPE GLYCOPROTEIN; FUSION INHIBITOR T-20; BINDING-SITE; POTENT
   NEUTRALIZATION; CRYSTAL-STRUCTURE; ENV CLONES; PHAGE; VALIDATION
AB Many of the neutralising antibodies, isolated to date, display limited activities against the globally most prevalent HIV-1 subtypes A and C. Therefore, those subtypes are considered to be an important target for antibody-based therapy. Variable domains of llama heavy chain antibodies (VHH) have some superior properties compared with classical antibodies. Therefore we describe the application of trimeric forms of envelope proteins (Env), derived from HIV-1 of subtype A and B/C, for a prolonged immunization of two llamas. A panel of VHH, which interfere with CD4 binding to HIV-1 Env were selected with use of panning. The results of binding and competition assays to various Env, including a variant with a stabilized CD4-binding state (gp120(Ds2)), cross-competition experiments, maturation analysis and neutralisation assays, enabled us to classify the selected VHH into three groups. The VHH of group I were efficient mainly against viruses of subtype A, C and B'/C. The VHH of group II resemble the broadly neutralising antibody (bnmAb) b12, neutralizing mainly subtype B and C viruses, however some had a broader neutralisation profile. A representative of the third group, 2E7, had an even higher neutralization breadth, neutralizing 21 out of the 26 tested strains belonging to the A, A/G, B, B/C and C subtypes. To evaluate the contribution of certain amino acids to the potency of the VHH a small set of the mutants were constructed. Surprisingly this yielded one mutant with slightly improved neutralisation potency against 92UG37.A9 (subtype A) and 96ZM651.02 (subtype C). These findings and the well-known stability of VHH indicate the potential application of these VHH as anti-HIV-1 microbicides.
C1 [Strokappe, Nika; Szynol, Agnieszka; Gorlani, Andrea; de Haard, Hans; Verrips, Theo] Univ Utrecht, Dept Biol, Fac Sci, Utrecht, Netherlands.
   [Aasa-Chapman, Marlen; Quigley, Anna Forsman; Weiss, Robin] UCL, Div Infect & Immun, UCL MRC Ctr Med Mol Virol, London, England.
   [Hulsik, David Lutje] Univ Grenoble 1, EMBL, CNRS, Unit Virus Host Cell Interact UVHCI,UMI 3265, Grenoble, France.
   [Chen, Lei] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Strokappe, N (reprint author), Univ Utrecht, Dept Biol, Fac Sci, Utrecht, Netherlands.
EM t.verrips@qvquality.com
RI gorlani, andrea/C-5678-2014
FU Collaboration for AIDS Vaccine Discovery Grant [38637]; Bill & Melinda
   Gates Foundation; European Commission
FX This study was funded in part by the Collaboration for AIDS Vaccine
   Discovery Grant number 38637 sponsored by the Bill & Melinda Gates
   Foundation (http://www.gatesfoundation.org/Pages/home.aspx); as well as
   the European Commission 6th Frame Work Programme as part of the European
   Microbicides Project (EMPRO; www.empro.org.uk) and the European
   Commission under the 7th Framework Programme as part of the Combined
   Highly Active Anti-Retroviral Microbicides (CHAARM; http://chaarm.eu/).
   The funders had no role in study design, data collection and analysis,
   decision to publish, or preparation of the manuscript.
NR 74
TC 22
Z9 25
U1 0
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 MAR 15
PY 2012
VL 7
IS 3
AR e33298
DI 10.1371/journal.pone.0033298
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 932RU
UT WOS:000303309000020
PM 22438910
ER

PT J
AU Jiao, GS
   Kim, S
   Moayeri, M
   Crown, D
   Thai, A
   Cregar-Hernandez, L
   McKasson, L
   Sankaran, B
   Lehrer, A
   Wong, T
   Johns, L
   Margosiak, SA
   Leppla, SH
   Johnson, AT
AF Jiao, Guan-Sheng
   Kim, Seongjin
   Moayeri, Mahtab
   Crown, Devorah
   Thai, April
   Cregar-Hernandez, Lynne
   McKasson, Linda
   Sankaran, Banumathi
   Lehrer, Axel
   Wong, Teri
   Johns, Lisa
   Margosiak, Stephen A.
   Leppla, Stephen H.
   Johnson, Alan T.
TI Antidotes to anthrax lethal factor intoxication. Part 3: Evaluation of
   core structures and further modifications to the C2-side chain
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Anthrax; Lethal factor; Inhibitor; In vitro ADME; X-ray crystallography
ID INHALATIONAL ANTHRAX; KINASE-KINASE; INHIBITORS; TOXIN
AB Four core structures capable of providing sub-nanomolar inhibitors of anthrax lethal factor (LF) were evaluated by comparing the potential for toxicity, physicochemical properties, in vitro ADME profiles, and relative efficacy in a rat lethal toxin (LT) model of LF intoxication. Poor efficacy in the rat LT model exhibited by the phenoxyacetic acid series (3) correlated with low rat microsome and plasma stability. Specific molecular interactions contributing to the high affinity of inhibitors with a secondary amine in the C2-side chain were revealed by X-ray crystallography. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Jiao, Guan-Sheng; Kim, Seongjin; Thai, April; Cregar-Hernandez, Lynne; McKasson, Linda; Lehrer, Axel; Wong, Teri; Johns, Lisa; Margosiak, Stephen A.; Johnson, Alan T.] PanThera Biopharma LLC, Aiea, HI 96701 USA.
   [Moayeri, Mahtab; Crown, Devorah; Leppla, Stephen H.] NIAID, Lab Bacterial Dis, NIH, Bethesda, MD 20892 USA.
   [Sankaran, Banumathi] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Adv Light Source, Berkeley, CA 94720 USA.
RP Johnson, AT (reprint author), PanThera Biopharma LLC, Aiea, HI 96701 USA.
EM ajohnson@pantherabio.com
FU National Institutes of Health [R44 AI052587, U01 AI078067]; National
   Institute of Allergy and Infectious Diseases
FX We thank the National Institutes of Health for their support of this
   work with Grants R44 AI052587 and U01 AI078067. The rat LT challenge
   studies were supported by the Intramural Research Program of the NIH,
   National Institute of Allergy and Infectious Diseases. The PK study was
   conducted by Covance Laboratories, Inc. (Madison, WI). The content is
   solely the responsibility of the authors and does not necessarily
   represent the official views of the NIAID or the NIH.
NR 20
TC 10
Z9 11
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD MAR 15
PY 2012
VL 22
IS 6
BP 2242
EP 2246
DI 10.1016/j.bmcl.2012.01.095
PG 5
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 905PU
UT WOS:000301285500023
PM 22342144
ER

PT J
AU Ghosh, AK
   Chapsal, BD
   Steffey, M
   Agniswamy, J
   Wang, YF
   Amano, M
   Weber, IT
   Mitsuya, H
AF Ghosh, Arun K.
   Chapsal, Bruno D.
   Steffey, Melinda
   Agniswamy, Johnson
   Wang, Yuan-Fang
   Amano, Masayuki
   Weber, Irene T.
   Mitsuya, Hiroaki
TI Substituent effects on P2-cyclopentyltetrahydrofuranyl urethanes:
   Design, synthesis, and X-ray studies of potent HIV-1 protease inhibitors
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE HIV-1 protease inhibitors; P2 ligand; Drug resistance; Design and
   synthesis; X-ray crystal structure
ID DRUG-RESISTANT MUTANTS; BIOLOGICAL EVALUATION; CRYSTAL-STRUCTURE;
   COMPLEXES; P2-LIGANDS; BACKBONE; TMC114
AB The design, synthesis, and biological evaluation of novel C3-substituted cyclopentyltetrahydrofuranyl (Cp-THF)-derived HIV-1 protease inhibitors are described. Various C3-functional groups on the Cp-THF ligand were investigated in order to maximize the ligand-binding site interactions in the flap region of the protease. Inhibitors 3c and 3d have displayed the most potent enzyme inhibitory and antiviral activity. Both inhibitors have maintained impressive activity against a panel of multidrug resistant HIV-1 variants. A high-resolution X-ray crystal structure of 3c-bound HIV-1 protease revealed a number of important molecular insights into the ligand-binding site interactions. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Ghosh, Arun K.; Chapsal, Bruno D.; Steffey, Melinda] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA.
   [Ghosh, Arun K.; Chapsal, Bruno D.; 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, Dept Hematol, Grad Sch Med & Pharmaceut Sci, Kumamoto 8608556, Japan.
   [Amano, Masayuki; Mitsuya, Hiroaki] Kumamoto Univ, Dept Infect Dis, Grad Sch Med & Pharmaceut Sci, 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 Ghartouchent, malek/B-9088-2012; 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
   of Monbu-Kagakusho
FX This research was supported by the National Institutes of Health (Grant
   GM53386 to A.K.G. and Grant GM62920 to I.T.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 20
TC 12
Z9 13
U1 0
U2 12
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD MAR 15
PY 2012
VL 22
IS 6
BP 2308
EP 2311
DI 10.1016/j.bmcl.2012.01.061
PG 4
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 905PU
UT WOS:000301285500037
PM 22364812
ER

PT J
AU Schuit, E
   Stock, S
   Groenwold, RHH
   Maurel, K
   Combs, CA
   Garite, T
   Spong, CY
   Thom, EA
   Rouse, DJ
   Caritis, SN
   Saade, GR
   Zachary, JM
   Norman, JE
   Rode, L
   Klein, K
   Tabor, A
   Cetingoz, E
   Morrison, JC
   Magann, EF
   Briery, CM
   Serra, V
   Perales, A
   Meseguer, J
   Nassar, AH
   Lim, AC
   Moons, KGM
   Kwee, A
   Mol, BWJ
AF Schuit, Ewoud
   Stock, Sarah
   Groenwold, Rolf H. H.
   Maurel, Kimberly
   Combs, C. Andrew
   Garite, Thomas
   Spong, Cathy Y.
   Thom, Elizabeth A.
   Rouse, Dwight J.
   Caritis, Steve N.
   Saade, George R.
   Zachary, Julia M.
   Norman, Jane E.
   Rode, Line
   Klein, Katharina
   Tabor, Ann
   Cetingoz, Elcin
   Morrison, John C.
   Magann, Everett F.
   Briery, Christian M.
   Serra, Vicente
   Perales, Alfredo
   Meseguer, Juan
   Nassar, Anwar H.
   Lim, Arianne C.
   Moons, Karel G. M.
   Kwee, Anneke
   Mol, Ben Willem J.
TI Progestogens to prevent preterm birth in twin pregnancies: an individual
   participant data meta-analysis of randomized trials
SO BMC PREGNANCY AND CHILDBIRTH
LA English
DT Article
ID PATIENT DATA; 17-ALPHA-HYDROXYPROGESTERONE CAPROATE; DOUBLE-BLIND;
   PROGESTERONE; WOMEN; RISK
AB Background: Preterm birth is the principal factor contributing to adverse outcomes in multiple pregnancies. Randomized controlled trials of progestogens to prevent preterm birth in twin pregnancies have shown no clear benefits. However, individual studies have not had sufficient power to evaluate potential benefits in women at particular high risk of early delivery (for example, women with a previous preterm birth or short cervix) or to determine adverse effects for rare outcomes such as intrauterine death.
   Methods/design: We propose an individual participant data meta-analysis of high quality randomized, double-blind, placebo-controlled trials of progestogen treatment in women with a twin pregnancy. The primary outcome will be adverse perinatal outcome (a composite measure of perinatal mortality and significant neonatal morbidity). Missing data will be imputed within each original study, before data of the individual studies are pooled. The effects of 17-hydroxyprogesterone caproate or vaginal progesterone treatment in women with twin pregnancies will be estimated by means of a random effects log-binomial model. Analyses will be adjusted for variables used in stratified randomization as appropriate. Pre-specified subgroup analysis will be performed to explore the effect of progestogen treatment in high-risk groups.
   Discussion: Combining individual patient data from different randomized trials has potential to provide valuable, clinically useful information regarding the benefits and potential harms of progestogens in women with twin pregnancy overall and in relevant subgroups.
C1 [Schuit, Ewoud; Groenwold, Rolf H. H.; Moons, Karel G. M.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
   [Stock, Sarah; Norman, Jane E.] Univ Edinburgh, MC Ctr Reprod Hlth, Edinburgh, Midlothian, Scotland.
   [Maurel, Kimberly] CREQ, Obstetrix Med Grp, Fountain Valley, CA USA.
   [Combs, C. Andrew] Obstetrix Med Grp, San Jose, CA USA.
   [Garite, Thomas] CREQ, Obstetrix Med Grp, Steamboat Springs, CO USA.
   [Spong, Cathy Y.] NICHHD, Bethesda, MD 20892 USA.
   [Thom, Elizabeth A.; Zachary, Julia M.] George Washington Univ, Ctr Biostat, Rockville, MD USA.
   [Rouse, Dwight J.] Brown Univ, Dept Obstet & Gynecol, Providence, RI 02912 USA.
   [Caritis, Steve N.] Univ Pittsburgh, Magee Womens Hosp, Dept Obstet & Gynecol, Pittsburgh, PA 15213 USA.
   [Saade, George R.] Univ Texas Med Branch, Dept Obstet & Gynecol, Galveston, TX USA.
   [Rode, Line; Tabor, Ann] Rigshosp, Copenhagen Univ Hosp, Dept Fetal Med 4002, DK-2100 Copenhagen, Denmark.
   [Klein, Katharina] Med Univ Vienna, Dept Obstet & Feto Maternal, Vienna, Austria.
   [Cetingoz, Elcin] Zeynep Kamil Women & Children Dis Educ & Res Hosp, Dept Obstet & Gynecol, Istanbul, Turkey.
   [Morrison, John C.] Univ Mississippi, Med Ctr, Dept Obstet & Gynecol, Jackson, MS USA.
   [Magann, Everett F.] Univ Arkansas Med Sci, Dept Obstet & Gynecol, Little Rock, AR 72205 USA.
   [Briery, Christian M.] Willis Knighton Med Ctr, Dept Obstet & Gynecol, Shreveport, LA USA.
   [Serra, Vicente] Univ Valencia, Inst Valenciano Infertilidad, Maternal Fetal Med Unit, Valencia, Spain.
   [Perales, Alfredo] Univ Hosp La Fe, Dept Obstet & Gynecol, Valencia, Spain.
   [Meseguer, Juan] Hosp Univ Virgen de la Arrixaca, Dept Obstet & Ginecol, Murcia, Spain.
   [Nassar, Anwar H.] Amer Univ Beirut, Dept Obstet & Gynecol, Beirut, Lebanon.
   [Lim, Arianne C.; Mol, Ben Willem J.] Univ Amsterdam, Acad Med Ctr, Dept Obstet & Gynecol, NL-1105 AZ Amsterdam, Netherlands.
   [Kwee, Anneke] Univ Med Ctr Utrecht, Dept Obstet & Gynecol, Utrecht, Netherlands.
RP Schuit, E (reprint author), Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
EM e.schuit@umcutrecht.nl
RI Mol, Ben /I-4526-2012; 
OI Combs, C Andrew/0000-0002-5571-9579; caritis, steve/0000-0002-2169-0712
FU Medical Research Council [G1002033]; NICHD NIH HHS [U10 HD036801]
NR 27
TC 8
Z9 8
U1 0
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2393
J9 BMC PREGNANCY CHILDB
JI BMC Pregnancy Childbirth
PD MAR 15
PY 2012
VL 12
AR 13
DI 10.1186/1471-2393-12-13
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 919XH
UT WOS:000302365000001
PM 22420582
ER

PT J
AU Kim, G
   Davidson, B
   Henning, R
   Wang, JB
   Yu, MS
   Annunziata, C
   Hetland, T
   Kohn, EC
AF Kim, Geoffrey
   Davidson, Ben
   Henning, Ryan
   Wang, Junbai
   Yu, Minshu
   Annunziata, Christina
   Hetland, Thea
   Kohn, Elise C.
TI Adhesion molecule protein signature in ovarian cancer effusions is
   prognostic of patient outcome
SO CANCER
LA English
DT Article
DE adhesion molecules; ascites; ovarian cancer; proteomics array
ID E-CADHERIN EXPRESSION; CELL-CELL ADHESION; ADHERENS JUNCTIONS; PROTEOMIC
   ANALYSIS; MALIGNANT ASCITES; CARCINOMA CELLS; BETA-CATENIN; TUMOR-CELLS;
   PHASE-II; ANOIKIS
AB BACKGROUND: Ovarian cancer cells in malignant effusions lack attachment to solid-phase matrix substrata and receive survival stimuli through cellcell and cellsoluble matrix molecule interactions. We hypothesized that adhesion-related survival and proliferation pathway signals can inform clinical outcomes and guide targeted therapeutics. METHODS: Lysed cell pellets from a blinded set of benign (n 20) and malignant (n 51) peritoneal and pleural ovarian cancer patient effusions were applied to reverse-phase protein arrays and examined using validated antibodies to adhesion-associated protein endpoints. Results were subjected to hierarchical clustering for signature development. Association between specimen type, protein expression, and clinicopathologic associations were analyzed using the Mann-Whitney U test. Survival outcomes were estimated using the Kaplan-Meier method with log-rank comparison. RESULTS: A cell adhesion protein signature obtained from unsupervised clustering distinguished malignant from benign effusions (P 6.18E-06). Protein subset analyses from malignant cases defined 3 cell adhesion protein clusters driven by E-cadherin, epithelial cell adhesion molecule, and N-cadherin, respectively. The components of the E-and N-cadherin clusters correlated with clinical outcome by Kaplan-Meier statistics. Univariate analysis indicated that FAK and phosphorylated AKT were associated with higher overall and progression-free survival (PFS) (P.03), and Akt, phosphorylated paxillin, and E-and N-cadherin were associated with improved PFS (P .05). If 4 or 5 of the index adhesion proteins were high, PFS was improved by multivariate analysis (P .01). CONCLUSIONS: This hypothesis-testing examination of tumor cell adhesion molecules and pathways yielded potential predictive biomarkers with which to triage patients to selected molecular therapeutics and may serve as a platform for biomarker-based stratification for clinical application. Cancer 2012; 118: 1543-53. Published 2011 by the American Cancer Society*.
C1 [Kim, Geoffrey; Henning, Ryan; Yu, Minshu; Annunziata, Christina; Kohn, Elise C.] NCI, Mol Signaling Sect, Med Oncol Branch, Bethesda, MD 20892 USA.
   [Davidson, Ben; Wang, Junbai; Hetland, Thea] Oslo Univ Hosp, Norwegian Radium Hosp, Div Pathol, Oslo, Norway.
   [Hetland, Thea] Oslo Univ Hosp, Norwegian Radium Hosp, Dept Gynecol Oncol, Oslo, Norway.
   [Davidson, Ben] Univ Oslo, Fac Med, Oslo, Norway.
RP Kohn, EC (reprint author), 10 Ctr Dr,MSC 1906, Bethesda, MD 20892 USA.
EM kohne@mail.nih.gov
RI Wang, Junbai/B-2093-2008; Annunziata, Christina/L-3219-2016
OI Annunziata, Christina/0000-0003-2033-6532
FU Center for Cancer Research, National Cancer Institute; Norwegian Cancer
   Society; Inger and John Fredriksen Foundation for Ovarian Cancer
   Research
FX This study was supported by the Intramural Program of the Center for
   Cancer Research, National Cancer Institute, and by a grant from the
   Norwegian Cancer Society and by the Inger and John Fredriksen Foundation
   for Ovarian Cancer Research.
NR 51
TC 7
Z9 7
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD MAR 15
PY 2012
VL 118
IS 6
BP 1543
EP 1553
DI 10.1002/cncr.26449
PG 11
WC Oncology
SC Oncology
GA 901NE
UT WOS:000300973000010
PM 22009736
ER

PT J
AU Brosh, RM
AF Brosh, Robert M.
TI Finding a needle in the haystack Recognition of DNA damage by
   collaboration between DNA repair proteins able to perform DNA charge
   transport
SO CELL CYCLE
LA English
DT Editorial Material
C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
RP Brosh, RM (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
EM broshr@mail.nih.gov
NR 10
TC 0
Z9 0
U1 1
U2 2
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD MAR 15
PY 2012
VL 11
IS 6
BP 1055
EP 1056
DI 10.4161/cc.11.6.19785
PG 2
WC Cell Biology
SC Cell Biology
GA 913DD
UT WOS:000301851700004
PM 22377696
ER

PT J
AU Shizukuda, Y
   Tripodi, DJ
   Zalos, G
   Bolan, CD
   Yau, YY
   Leitman, SF
   Waclawiw, MA
   Rosing, DR
AF Shizukuda, Yukitaka
   Tripodi, Dorothy J.
   Zalos, Gloria
   Bolan, Charles D.
   Yau, Yu-Ying
   Leitman, Susan F.
   Waclawiw, Myron A.
   Rosing, Douglas R.
TI Incidence of Cardiac Arrhythmias in Asymptomatic Hereditary
   Hemochromatosis Subjects With C282Y Homozygosity
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID IRON OVERLOAD CARDIOMYOPATHY; FIBRILLATION; MANAGEMENT; EXERCISE; STRESS
AB It is not well known whether systemic iron overload per se in hereditary hemochromatosis (HH) is associated with cardiac arrhythmias before other signs and symptoms of cardiovascular disease occur. In the present study, we examined the incidence of cardiac arrhythmia in cardiac asymptomatic subjects with HH (New York Heart Association functional class I) and compared it to that in age- and gender-matched normal volunteers. The 42 subjects with HH and the 19 normal control subjects were recruited through the National Heart, Lung, and Blood Institute-sponsored "Heart Study of Hemochromatosis." They completed 48-hour Holter electrocardiography ambulatory monitoring at the baseline evaluation. The subjects with HH were classified as newly diagnosed (group A) and chronically treated (group B) subjects. All subjects with HH had C282Y homozygosity, and the normal volunteers lacked any HFE gene mutations known to cause HH. Although statistically insignificant, the incidence of ventricular and supraventricular ectopy tended to be greater in the combined HH groups than in the controls. Supraventricular ectopy was more frequently noted in group B compared to in the controls (ectopy rate per hour 11.1 +/- 29.9 vs 1.5 +/- 3.5, p < 0.05, using the Kruskal-Wallis test). No examples of heart block, other than first-degree atrioventricular node block, were seen in any of the subjects. The incidence of cardiac arrhythmias was not significantly reduced after 6 months of intensive iron removal therapy in the group A subjects. No life-threatening arrhythmias were observed in our subjects with HH. In conclusion, our data suggest that the incidence of cardiac arrhythmias is, at most, marginally increased in asymptomatic subjects with HH. A larger clinical study is warranted to further clarify our observation. Published by Elsevier Inc. (Am J Cardiol 2012;109:856-860)
C1 [Shizukuda, Yukitaka; Tripodi, Dorothy J.; Zalos, Gloria; Rosing, Douglas R.] NHLBI, Cardiopulm Branch, Bethesda, MD 20892 USA.
   [Waclawiw, Myron A.] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
   [Bolan, Charles D.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA.
   [Yau, Yu-Ying; Leitman, Susan F.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
   [Shizukuda, Yukitaka] Univ Cincinnati, Div Cardiovasc Med, Cincinnati, OH USA.
   [Shizukuda, Yukitaka] Cincinnati Vet Affairs Med Ctr, Cincinnati, OH USA.
RP Shizukuda, Y (reprint author), NHLBI, Cardiopulm Branch, Bldg 10, Bethesda, MD 20892 USA.
EM shizukya@uc.edu
FU National Heart, Lung, and Blood Institute, National Institutes of
   Health, Bethesda, Maryland
FX This study was funded by intramural programs of the National Heart,
   Lung, and Blood Institute, National Institutes of Health, Bethesda,
   Maryland.
NR 19
TC 4
Z9 5
U1 0
U2 0
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD MAR 15
PY 2012
VL 109
IS 6
BP 856
EP 860
DI 10.1016/j.amjcard.2011.11.011
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 914QV
UT WOS:000301967500013
PM 22196777
ER

PT J
AU Chandan, K
   van Iersel, MP
   Aladjem, MI
   Kohn, KW
   Luna, A
AF Chandan, Kumar
   van Iersel, Martijn P.
   Aladjem, Mirit I.
   Kohn, Kurt W.
   Luna, Augustin
TI PathVisio-Validator: a rule-based validation plugin for graphical
   pathway notations
SO BIOINFORMATICS
LA English
DT Article
ID BIOLOGICAL PATHWAYS; MARKUP LANGUAGE; EXCHANGE; FORMAT; MAPS
AB Purpose: The PathVisio-Validator plugin aims to simplify the task of producing biological pathway diagrams that follow graphical standardized notations, such as Molecular Interaction Maps or the Systems Biology Graphical Notation. This plugin assists in the creation of pathway diagrams by ensuring correct usage of a notation, and thereby reducing ambiguity when diagrams are shared among biologists. Rulesets, needed in the validation process, can be generated for any graphical notation that a developer desires, using either Schematron or Groovy. The plugin also provides support for filtering validation results, validating on a subset of rules, and distinguishing errors and warnings.
   Availability: The PathVisio-Validator plugin works with versions of PathVisio 2.0.11 and later on Windows, Mac OS X and Linux. The plugin along with the instructions, example rulesets for Groovy and Schematron, and Java source code can be downloaded at http://pathvisio.org/wiki/PathVisioValidatorHelp. The software is developed under the open-source Apache 2.0 License and is freely available for both commercial and academic use.
C1 [Chandan, Kumar] Keshav Mem Inst Technol, Hyderabad, Andhra Pradesh, India.
   [van Iersel, Martijn P.] BiGCaT Maastricht Univ, Dept Bioinformat, NL-6229 ER Maastricht, Netherlands.
   [Aladjem, Mirit I.; Kohn, Kurt W.; Luna, Augustin] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Luna, Augustin] Boston Univ, Bioinformat Program, Boston, MA 02215 USA.
RP Chandan, K (reprint author), Keshav Mem Inst Technol, Hyderabad, Andhra Pradesh, India.
EM chandankmit@gmail.com; augustin@mail.nih.gov
RI Aladjem, Mirit/G-2169-2010; van Iersel, Martijn/E-9105-2010
OI Aladjem, Mirit/0000-0002-1875-3110; van Iersel,
   Martijn/0000-0002-5877-4338
FU Google; National Institutes of Health, Center for Cancer Research,
   National Cancer Institute; Netherlands Consortium for Systems Biology
   (NCSB), Netherlands Genomics Initiative/Netherlands Organization for
   Scientific Research
FX Funding: Google Summer of Code program, Intramural Research Program of
   the National Institutes of Health, Center for Cancer Research, National
   Cancer Institute; Netherlands Consortium for Systems Biology (NCSB),
   which is part of the Netherlands Genomics Initiative/Netherlands
   Organization for Scientific Research, in part.
NR 8
TC 3
Z9 3
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
J9 BIOINFORMATICS
JI Bioinformatics
PD MAR 15
PY 2012
VL 28
IS 6
BP 889
EP 890
DI 10.1093/bioinformatics/btr694
PG 2
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 914SQ
UT WOS:000301972900023
PM 22199389
ER

PT J
AU Stojmirovic, A
   Bliskovsky, A
   Yu, YK
AF Stojmirovic, Aleksandar
   Bliskovsky, Alexander
   Yu, Yi-Kuo
TI CytoSaddleSum: a functional enrichment analysis plugin for Cytoscape
   based on sum-of-weights scores
SO BIOINFORMATICS
LA English
DT Article
AB CytoSaddleSum provides Cytoscape users with access to the functionality of SaddleSum, a functional enrichment tool based on sum-of-weight scores. It operates by querying SaddleSum locally (using the standalone version) or remotely (through an HTTP request to a web server). The functional enrichment results are shown as a term relationship network, where nodes represent terms and edges show term relationships. Furthermore, query results are written as Cytoscape attributes allowing easy saving, retrieval and integration into network-based data analysis workflows.
C1 [Stojmirovic, Aleksandar; Bliskovsky, Alexander; Yu, Yi-Kuo] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Yu, YK (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM yyu@ncbi.nlm.nih.gov
OI Stojmirovic, Aleksandar/0000-0003-0957-6893
FU National Library of Medicine at National Institutes of Health
FX Funding: Intramural Research Program of the National Library of Medicine
   at National Institutes of Health.
NR 7
TC 2
Z9 2
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
J9 BIOINFORMATICS
JI Bioinformatics
PD MAR 15
PY 2012
VL 28
IS 6
BP 893
EP 894
DI 10.1093/bioinformatics/bts041
PG 2
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 914SQ
UT WOS:000301972900025
PM 22345616
ER

PT J
AU Nandurdikar, RS
   Maciag, AE
   Cao, Z
   Keefer, LK
   Saavedra, JE
AF Nandurdikar, Rahul S.
   Maciag, Anna E.
   Cao, Zhao
   Keefer, Larry K.
   Saavedra, Joseph E.
TI Diazeniumdiolated carbamates: A novel class of nitric oxide donors
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Nitric oxide; Diazeniumdiolate prodrugs; Diazeniumdiolated carbamates;
   TOM protecting group; Intracellular nitric oxide
ID NITROXYL; PRODRUG; HNO
AB We report an indirect method for synthesis of previously inaccessible diazeniumdiolated carbamates. Synthesis involves use of previously reported triisopropylsilyloxymethylated isopropylamine diazeniumdiolate (TOM-ylated IPA/NO). These novel diazeniumdiolated carbamate prodrugs upon activation release nitric oxide (NO) similar to their secondary amine counterparts. They are also efficient sources of intracellular NO. These prodrugs may have potential applications as therapeutic NO-donors. (C) 2012 Elsevier Ltd. All rights
C1 [Nandurdikar, Rahul S.; Keefer, Larry K.] NCI, Drug Design Sect, Biol Chem Lab, Frederick, MD 21702 USA.
   [Maciag, Anna E.; Cao, Zhao; Saavedra, Joseph E.] NCI, Basic Sci Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Nandurdikar, RS (reprint author), NCI, Drug Design Sect, Biol Chem Lab, Frederick, MD 21702 USA.
EM nandurdikarr@mail.nih.gov; saavedjo@mail.nih.gov
RI Keefer, Larry/N-3247-2014
OI Keefer, Larry/0000-0001-7489-9555
FU National Cancer Institute, National Institutes of Health
   [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer
   Research
FX This project has been funded with Federal funds from the National Cancer
   Institute, National Institutes of Health, under contract
   HHSN261200800001E and by the Intramural Research Program of the NIH,
   National Cancer Institute, Center for Cancer Research. We thank Dr.
   Sergey Tarasov and Ms. Marzena A. Dyba of the Biophysics Resource in the
   Structural Biophysics Laboratory, NCI-Frederick, for assistance with the
   high resolution mass spectrometry studies.
NR 11
TC 10
Z9 10
U1 2
U2 10
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD MAR 15
PY 2012
VL 20
IS 6
BP 2025
EP 2029
DI 10.1016/j.bmc.2012.01.046
PG 5
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
   Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 904MJ
UT WOS:000301201100023
PM 22356735
ER

PT J
AU Ang, R
   Sebastian, S
   Ludwig, A
   Birnbaumer, L
   Tinker, A
AF Ang, R.
   Sebastian, S.
   Ludwig, A.
   Birnbaumer, L.
   Tinker, A.
TI Mice with conditional knockout of Galphai2 in the cardiac pacemaker
   system exhibit tachycardia with loss of HF power on HRV analysis
SO CARDIOVASCULAR RESEARCH
LA English
DT Meeting Abstract
CT 2nd Congress of the European-Society-of-Cardiology Council on Basic
   Cardiovascular Science - Frontiers in Cardiovascular Biology
CY MAR 30-APR 01, 2012
CL London, ENGLAND
SP European Soc Cardiol
C1 [Ang, R.] UCL, Ctr Clin Pharmacol, London, England.
   [Sebastian, S.; Tinker, A.] Barts & London Queen Marys Sch Med & Dent, London, England.
   [Ludwig, A.] Univ Erlangen Nurnberg, Inst Expt & Clin Pharmacol & Toxicol, D-91054 Erlangen, Germany.
   [Birnbaumer, L.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0008-6363
J9 CARDIOVASC RES
JI Cardiovasc. Res.
PD MAR 15
PY 2012
VL 93
SU 1
BP S20
EP S20
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 914TQ
UT WOS:000301975800070
ER

PT J
AU Menazza, SM
   Canton, MC
   Di Lisa, FDL
   Schulz, RS
AF Menazza, S. M.
   Canton, M. C.
   Di Lisa, F. D. L.
   Schulz, R. S.
TI Oxidation of specific plasma proteins is directly correlated with
   oxidative derangement of myofibrillar proteins in pacing-induced failure
   of rabbit hearts
SO CARDIOVASCULAR RESEARCH
LA English
DT Meeting Abstract
CT 2nd Congress of the European-Society-of-Cardiology Council on Basic
   Cardiovascular Science - Frontiers in Cardiovascular Biology
CY MAR 30-APR 01, 2012
CL London, ENGLAND
SP European Soc Cardiol
C1 [Menazza, S. M.] NHLBI, NIH, Bethesda, MD 20892 USA.
   [Canton, M. C.; Di Lisa, F. D. L.] Univ Padua, Dept Biomed Sci, Padua, Italy.
   [Schulz, R. S.] Univ Giessen, Inst Physiol, Giessen, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0008-6363
J9 CARDIOVASC RES
JI Cardiovasc. Res.
PD MAR 15
PY 2012
VL 93
SU 1
BP S85
EP S85
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 914TQ
UT WOS:000301975800364
ER

PT J
AU Molica, F
   Burger, F
   Matter, CM
   Thomas, A
   Staub, C
   Zimmer, A
   Cravatt, B
   Pacher, P
   Steffens, S
AF Molica, F.
   Burger, F.
   Matter, C. M.
   Thomas, A.
   Staub, C.
   Zimmer, A.
   Cravatt, B.
   Pacher, P.
   Steffens, S.
TI CB1 cannabinoid receptor antagonism inhibits balloon-induced neointima
   formation in atherosclerotic mice
SO CARDIOVASCULAR RESEARCH
LA English
DT Meeting Abstract
CT 2nd Congress of the European-Society-of-Cardiology Council on Basic
   Cardiovascular Science - Frontiers in Cardiovascular Biology
CY MAR 30-APR 01, 2012
CL London, ENGLAND
SP European Soc Cardiol
C1 [Molica, F.; Burger, F.; Steffens, S.] Univ Hosp Geneva, Geneva, Switzerland.
   [Matter, C. M.] Univ Zurich, Inst Physiol, Zurich, Switzerland.
   [Thomas, A.; Staub, C.] Univ Geneva, Fac Med, Inst Legal Med, Geneva, Switzerland.
   [Zimmer, A.] Univ Bonn, Inst Mol Psychiat, Bonn, Germany.
   [Cravatt, B.] Scripps Res Inst, La Jolla, CA 92037 USA.
   [Pacher, P.] NIH, Bethesda, MD 20892 USA.
RI Zimmer, Andreas/B-8357-2009; Filippo, Molica/A-6315-2013
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0008-6363
J9 CARDIOVASC RES
JI Cardiovasc. Res.
PD MAR 15
PY 2012
VL 93
SU 1
BP S119
EP S119
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 914TQ
UT WOS:000301975800511
ER

PT J
AU Kojima, H
   Muromoto, R
   Takahashi, M
   Takeuchi, S
   Takeda, Y
   Jetten, AM
   Matsuda, T
AF Kojima, Hiroyuki
   Muromoto, Ryuta
   Takahashi, Miki
   Takeuchi, Shinji
   Takeda, Yukimasa
   Jetten, Anton M.
   Matsuda, Tadashi
TI Inhibitory effects of azole-type fungicides on interleukin-17 gene
   expression via retinoic acid receptor-related orphan receptors alpha and
   gamma
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE Fungicide; Interleukin 17; Mouse; Reporter gene assay; Retinoic acid
   receptor-related orphan receptor
ID HAMSTER OVARY CELLS; ROR-GAMMA; T-CELLS; ANDROGEN RECEPTOR; NUCLEAR
   RECEPTORS; 200 PESTICIDES; DIFFERENTIATION; LIGAND; ESTROGEN; LINEAGE
AB The retinoic acid receptor-related orphan receptors alpha and gamma (ROR alpha and ROR gamma), are key regulators of helper T (Th)17 cell differentiation, which is involved in the innate immune system and autoimmune disorders. However, it remains unclear whether environmental chemicals, including pesticides, have agonistic and/or antagonistic activity against ROR alpha/gamma. In this study, we investigated the ROR alpha/gamma activity of several azole-type fungicides, and the effects of these fungicides on the gene expression of interleukin (IL)-17, which mediates the function of Th17 cells. In the ROR-reporter gene assays, five azole-type fungicides (imibenconazole, trifiumizole, hexaconazole, tetraconazole and imazalil) suppressed ROR alpha- and/or ROR gamma-mediated transcriptional activity as did benzenesulphonamide T0901317, a ROR inverse agonist and a liver X receptor (LXR) agonist. In particular, imibenconazole, triflumizole and hexaconazole showed ROR gamma inverse agonistic activity at concentrations of 10(-6) M. However, unlike T0901317, these fungicides failed to show any LXR alpha/beta agonistic activity. Next, five azole-type fungicides, showing ROR inverse agonist activity, were tested on IL-17 mRNA expression in mouse T lymphoma EL4 cells treated with phorbol myristate acetate and ionomycin. The quantitative RT-PCR analysis revealed that these fungicides suppressed the expression of IL-17 mRNA without effecting ROR alpha and ROR gamma mRNA levels. In addition, the inhibitory effect of imibenconazole as well as that of T0901317 was absorbed in ROR alpha/gamma-knocked down EL4 cells. Taken together, these results suggest that some azole-type fungicides inhibit IL-17 production via ROR alpha/gamma. This also provides the first evidence that environmental chemicals can act as modulators of IL-17 expression in immune cells. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Kojima, Hiroyuki; Takeuchi, Shinji] Hokkaido Inst Publ Hlth, Kita Ku, Sapporo, Hokkaido 0600819, Japan.
   [Muromoto, Ryuta; Takahashi, Miki; Matsuda, Tadashi] Hokkaido Univ, Grad Sch Pharmaceut Sci, Kita Ku, Sapporo, Hokkaido 0600812, Japan.
   [Takeda, Yukimasa; Jetten, Anton M.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
RP Kojima, H (reprint author), Hokkaido Inst Publ Hlth, Kita Ku, Kita 19,Nishi 12, Sapporo, Hokkaido 0600819, Japan.
EM kojima@iph.pref.hokkaido.jp
RI Matsuda, Tadashi/A-3835-2012; Muromoto, Ryuta/E-4203-2012; 
OI Jetten, Anton/0000-0003-0954-4445
FU Japan Society for the Promotion of Science (JSPS) [21590675]
FX We would like to thank Dr. Kaoru Kobayashi (Faculty of Pharmaceutical
   Sciences, Chiba University, Japan) for providing the plasmids for LXR
   alpha/beta assays. This study was supported by Grant-in-Aid for
   Scientific Research (C) (21590675) from the Japan Society for the
   Promotion of Science (JSPS).
NR 38
TC 15
Z9 17
U1 0
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0041-008X
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD MAR 15
PY 2012
VL 259
IS 3
BP 338
EP 345
DI 10.1016/j.taap.2012.01.011
PG 8
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 913QP
UT WOS:000301892800009
PM 22289359
ER

PT J
AU Yang, IV
   Tomfohr, J
   Singh, J
   Foss, CM
   Marshall, HE
   Que, LG
   McElvania-Tekippe, E
   Florence, S
   Sundy, JS
   Schwartz, DA
AF Yang, Ivana V.
   Tomfohr, John
   Singh, Jaspal
   Foss, Catherine M.
   Marshall, Harvey E.
   Que, Loretta G.
   McElvania-Tekippe, Erin
   Florence, Sarita
   Sundy, John S.
   Schwartz, David A.
TI The Clinical and Environmental Determinants of Airway Transcriptional
   Profiles in Allergic Asthma
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE environmental asthma; microarray; house dust mite; lipo-polysaccharide;
   atopy
ID PLASMA ADRENOMEDULLIN; SUSCEPTIBILITY GENES; PERIPHERAL-BLOOD; DISEASE;
   C3; HYPERRESPONSIVENESS; 5-LIPOXYGENASE; INFLAMMATION; ASSOCIATION;
   INVOLVEMENT
AB Rationale: Gene expression profiling of airway epithelial and inflammatory cells can be used to identify genes involved in environmental asthma.
   Methods: Airway epithelia and inflammatory cells were obtained via bronchial brush and bronchoalveolar lavage (BAL) from 39 subjects comprising three phenotypic groups (nonatopic nonasthmatic, atopic nonasthmatic, and atopic asthmatic) 4 hours after instillation of LPS, house dust mite antigen, and saline in three distinct subsegmental bronchi. RNA transcript levels were assessed using whole genome microarrays.
   Measurements and Main Results: Baseline (saline exposure) differences in gene expression were related to airflow obstruction in epithelial cells (C3, ALOX5AP, CCL18, and others), and to serum IgE (innate immune genes and focal adhesion pathway) and allergic-asthmatic phenotype (complement genes, histone deacetylases, and GATA1 transcription factor) in inflammatory cells. LPS stimulation resulted in pronounced transcriptional response across all subjects in both airway epithelia and BAL cells, with strong association to nuclear factor-kappa B and IFN-inducible genes as well as signatures of other transcription factors (NRF2, C/EBP, and E2F1) and histone proteins. No distinct transcriptional profile to LPS was observed in the asthma and atopy phenotype. Finally, although no consistent expression changes were observed across all subjects in response to house dust mite antigen stimulation, we observed subtle differences in gene expression (e.g., GATA1 and GATA2) in BAL cells related to the asthma and atopy phenotype.
   Conclusions: Our results indicate that among individuals with allergic asthma, transcriptional changes in airway epithelia and inflammatory cells are influenced by phenotype as well as environmental exposures.
C1 [Yang, Ivana V.; Schwartz, David A.] Univ Colorado Denver, Dept Med, Aurora, CO 80045 USA.
   [Yang, Ivana V.; Schwartz, David A.] Natl Jewish Hlth, Ctr Genes Environm & Hlth, Denver, CO USA.
   [Yang, Ivana V.; Schwartz, David A.] Natl Jewish Hlth, Dept Med, Denver, CO USA.
   [Tomfohr, John] NHLBI, Lab Environm Lung Dis, Bethesda, MD 20892 USA.
   [Singh, Jaspal; Foss, Catherine M.; Marshall, Harvey E.; Que, Loretta G.; McElvania-Tekippe, Erin; Florence, Sarita; Sundy, John S.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
RP Yang, IV (reprint author), Univ Colorado Denver, Dept Med, 12700 E 19th Ave,8611, Aurora, CO 80045 USA.
EM ivana.yang@ucdenver.edu
FU National Institute of Environmental Health Sciences [ES18181, ES011185,
   ES012496]; National Heart, Lung, and Blood Institute [HL082055];
   National Center for Research Resources, Clinical Research Centers
   [M01-RR-30]
FX Supported by the National Institute of Environmental Health Sciences
   (ES18181, ES011185, ES012496, and intramural funds); the National Heart,
   Lung, and Blood Institute (HL082055 and intramural funds); and the
   National Center for Research Resources, Clinical Research Centers
   Program (M01-RR-30).
NR 29
TC 12
Z9 12
U1 0
U2 2
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1073-449X
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD MAR 15
PY 2012
VL 185
IS 6
BP 620
EP 627
DI 10.1164/rccm.201108-1503OC
PG 8
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 910WP
UT WOS:000301674900008
PM 22246175
ER

PT J
AU Barkess, G
   Postnikov, Y
   Campos, CD
   Mishra, S
   Mohan, G
   Verma, S
   Bustin, M
   West, KL
AF Barkess, Grainne
   Postnikov, Yuri
   Campos, Chrisanne D.
   Mishra, Shivam
   Mohan, Gokula
   Verma, Sakshi
   Bustin, Michael
   West, Katherine L.
TI The chromatin-binding protein HMGN3 stimulates histone acetylation and
   transcription across the Glyt1 gene
SO BIOCHEMICAL JOURNAL
LA English
DT Article
DE acetylation; chromatin; elongation; epigenetics; HMGN; p300/CREB
   (cAMP-response-element-binding protein)-binding protein-associated
   factor (PCAF)
ID POLYMERASE-II ELONGATION; IN-VIVO; CHROMOSOMAL-PROTEINS;
   DOWN-REGULATION; GENOME BROWSER; CODING REGIONS; EXPRESSION;
   NUCLEOSOMES; HMG-14; H3
AB HMGNs are nucleosome-binding proteins that alter the pattern of histone modifications and modulate the binding of linker histones to chromatin. The HMGN3 family member exists as two splice forms. HMGN3a which is full-length and HMGN3b which lacks the C-terminal RD (regulatory domain). In the present study, we have used the Glyt1 (glycine transporter 1) gene as a model system to investigate where HMGN proteins are bound across the locus in vivo. and to study how the two HMGN3 splice variants affect histone modifications and gene expression. We demonstrate that HMGN1, HMGN2, HMGN3a and HMGN3b are bound across the Glyt1 gene locus and surrounding regions, and are not enriched more highly at the promoter or putative enhancer. We conclude that the peaks of H3K4me3 (trimethylated Lys(4) of histone H3) and H3K9ac (acetylated Lys(9) of histone H3) at the active Glyt1a promoter do not play a major role in recruiting HMGN proteins. HMGN3a/b binding leads to increased H3K14 (Lys(14) of histone H3) acetylation and stimulates Glyt1a expression, but does not alter the levels of H3K4me3 or H3K9ac enrichment. Acetylation assays show that HMGN3a stimulates the ability of PCAF [p300/CREB (cAMP-response-element-binding protein)binding protein-associated factor] to acetylate nucleosomal H3 in vitro, whereas HMGN3b does not. We propose a model where HMGN3a/b-stimulated H3K14 acetylation across the bodies of large genes such as Glyt1 can lead to more efficient transcription elongation and increased mRNA production.
C1 [Barkess, Grainne; Campos, Chrisanne D.; Mishra, Shivam; Mohan, Gokula; Verma, Sakshi; West, Katherine L.] Univ Glasgow, Coll Med Vet & Life Sci, Inst Canc Sci, Glasgow G11 6NT, Lanark, Scotland.
   [Postnikov, Yuri; Bustin, Michael] NCI, Lab Metab, CCR, NIH, Bethesda, MD 20892 USA.
RP West, KL (reprint author), Univ Glasgow, Coll Med Vet & Life Sci, Inst Canc Sci, Glasgow G11 6NT, Lanark, Scotland.
EM katherine.west@glasgow.ac.uk
RI Bustin, Michael/G-6155-2015; 
OI Barkess, Grainne/0000-0003-1742-921X
FU Biotechnology and Biological Sciences Research Council [BB/C006496/1];
   University of Malaya, Kuala Lumpur, Malaysia; International Cancer
   Research [07-01271]; European Community Marie Curie International
   Reintegration [0066521]; National Cancer Institute; National Institutes
   of Health
FX This work was supported by the Biotechnology and Biological Sciences
   Research Council [grant number BB/C006496/1]; the University of Malaya,
   Kuala Lumpur, Malaysia (Ph.D. funding to GM.); the Association for
   International Cancer Research [grant number 07-01271]; a European
   Community Marie Curie International Reintegration Grant [contract number
   0066521]; and the Centre for Cancer Research intramural program of the
   National Cancer Institute and National Institutes of Health.
NR 57
TC 7
Z9 8
U1 0
U2 6
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 MAR 15
PY 2012
VL 442
BP 495
EP 505
DI 10.1042/BJ20111502
PN 3
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 909JA
UT WOS:000301559600004
PM 22150271
ER

PT J
AU Zanetti, KA
   Haznadar, M
   Welsh, JA
   Robles, AI
   Ryan, BM
   McClary, AC
   Bowman, ED
   Goodman, JE
   Bernig, T
   Chanock, SJ
   Harris, CC
AF Zanetti, Krista A.
   Haznadar, Majda
   Welsh, Judith A.
   Robles, Ana I.
   Ryan, Brid M.
   McClary, Andrew C.
   Bowman, Elise D.
   Goodman, Julie E.
   Bernig, Toralf
   Chanock, Stephen J.
   Harris, Curtis C.
TI 3 '-UTR and Functional Secretor Haplotypes in Mannose-Binding Lectin 2
   Are Associated with Increased Colon Cancer Risk in African Americans
SO CANCER RESEARCH
LA English
DT Article
ID COLORECTAL-CANCER; GENETIC-VARIATION; COMPLEMENT ACTIVATION; PROTEIN
   LEVELS; POLYMORPHISMS; PATHWAY; DISEASE; POPULATION; VARIANTS; DATABASE
AB Because chronic intestinal inflammation is a risk factor for colorectal cancer, we hypothesized that genetic variants of inflammatory mediators, such as mannose-binding lectin 2 (MBL2), are associated with colon cancer susceptibility. Here, we report the association of 24 AIBL2 single-nucleotide polyrnorphisms (SNP) and corresponding haplotypes with colon cancer risk in a case-control study. Four SNPs in the 3'-untranslated region (UTR) of the gene (rs10082466, rs2120132, rs2099902, and rs10450310) were associated with an increased risk of colon cancer in African Americans. ORs for homozygous variants versus wild-type ranged from 3.17 [95% confidence interval (CI), 1.57-6.40] to 4.51 (95% CI, 1.94-10.50), whereas the 3'-UTR region haplotype consisting of these four variants had an OR of 2.10 (95% CI, 1.42-3.12). The C allele of rs10082466 exhibited a binding affinity of miR-27a and this allele was associated with both lower MBL plasma levels and activity. We found that 5' secretor haplotypes known to correlate with moderate and low MBI, serum levels exhibited associations with increased risk of colon cancer in African Americans, specifically as driven by two haplotypes, LYPA and LYQC, relative to the referent HATA haplotype (LYPA: OR, 2.60; 95% CI, 1.33-5.08 and LYQC: OR, 2.28; 95% CI, 1.20-4.30). Similar associations were not observed in Caucasians. Together, our results support the hypothesis that genetic variations in MBL2 increase colon cancer susceptibility in African Americans, Cancer Res,. 72(6); 1467-77.(C) 2012 AACR
C1 [Zanetti, Krista A.; Haznadar, Majda; Welsh, Judith A.; Robles, Ana I.; Ryan, Brid M.; McClary, Andrew C.; Bowman, Elise D.; Harris, Curtis C.] NCI, Lab Human Carcino genesis, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Zanetti, Krista A.] Div Canc Control & Populat Sci, Host Susceptibil Factors Branch, Epidemiol & Genom Res Program, Rockville, MD USA.
   [McClary, Andrew C.] Howard Hughes Med Inst, Chevy Chase, MD USA.
   [Goodman, Julie E.] Gradient Corp, Cambridge, MA 02138 USA.
   [Bernig, Toralf; Chanock, Stephen J.] Natl Canc Inst, Lab Translat Gen, Div Canc Epidemiol & Genet, Gaithersburg, MD USA.
RP Harris, CC (reprint author), NCI, Lab Human Carcino genesis, Ctr Canc Res, Bldg 37,Room 3068,37 Convent Dr,MSC 4258, Bethesda, MD 20892 USA.
EM Curtis_Harris@nih.gov
FU NIH; Center for Cancer Research, National Cancer Institute; National
   Institute on Minority Health and Health Disparities; Cancer Prevention
   Fellowship Program; Division of Cancer Prevention, National Cancer
   Institute
FX The work was supported by funding front the Intramural Research Program
   of the NIH, Center for Cancer Research, National Cancer Institute, and
   National Institute on Minority Health and Health Disparities and by
   funding from the Cancer Prevention Fellowship Program (2003-2007),
   Division of Cancer Prevention, National Cancer Institute to K.A.
   Zanetti.
NR 34
TC 24
Z9 26
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD MAR 15
PY 2012
VL 72
IS 6
BP 1467
EP 1477
DI 10.1158/0008-5472.CAN-11-3073
PG 11
WC Oncology
SC Oncology
GA 910UC
UT WOS:000301667300016
PM 22282660
ER

PT J
AU Bates, SE
AF Bates, Susan E.
TI Molecular Diagnostics: Are We There Yet?
SO CLINICAL CANCER RESEARCH
LA English
DT Editorial Material
C1 NCI, Bethesda, MD 20892 USA.
RP Bates, SE (reprint author), NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2012
VL 18
IS 6
BP 1514
EP 1514
DI 10.1158/1078-0432.CCR-11-2207
PG 1
WC Oncology
SC Oncology
GA 910VW
UT WOS:000301672400006
PM 22422402
ER

PT J
AU Poste, G
   Carbone, DP
   Parkinson, DR
   Verweij, J
   Hewitt, SM
   Jessup, JM
AF Poste, George
   Carbone, David P.
   Parkinson, David R.
   Verweij, Jaap
   Hewitt, Stephen M.
   Jessup, J. Milburn
TI Leveling the Playing Field: Bringing Development of Biomarkers and
   Molecular Diagnostics up to the Standards for Drug Development
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; INTEGRATED GENOMIC ANALYSIS; LIKELIHOOD
   RATIOS; LUNG-CANCER; TRIAL; MUTATIONS; IMATINIB; PATHWAYS; SURVIVAL;
   THERAPY
AB Molecular diagnostics are becoming increasingly important in clinical research to stratify or identify molecularly profiled patient cohorts for targeted therapies, to modify the dose of a therapeutic, and to assess early response to therapy or monitor patients. Molecular diagnostics can also be used to identify the pharmacogenetic risk of adverse drug reactions. The articles in this CCR Focus section on molecular diagnosis describe the development and use of markers to guide medical decisions regarding cancer patients. They define sources of preanalytic variability that need to be minimized, as well as the regulatory and financial challenges involved in developing diagnostics and integrating them into clinical practice. They also outline a National Cancer Institute program to assist diagnostic development. Molecular diagnostic clinical tests require rigor in their development and clinical validation, with sensitivity, specificity, and validity comparable to those required for the development of therapeutics. These diagnostics must be offered at a realistic cost that reflects both their clinical value and the costs associated with their development. When genome-sequencing technologies move into the clinic, they must be integrated with and traceable to current technology because they may identify more efficient and accurate approaches to drug development. In addition, regulators may define progressive drug approval for companion diagnostics that requires further evidence regarding efficacy and safety before full approval can be achieved. One way to accomplish this is to emphasize phase IV postmarketing, hypothesis-driven clinical trials with biological characterization that would permit an accurate definition of the association of low-prevalence gene alterations with toxicity or response in large cohorts. Clin Cancer Res; 18(6); 1515-23. (C)2012 AACR.
C1 [Poste, George] Arizona State Univ, Complex Adapt Syst Initiat, Scottsdale, AZ USA.
   [Carbone, David P.] Vanderbilt Ingram Canc Ctr, Thorac Head & Neck Program, Nashville, TN USA.
   [Carbone, David P.] Vanderbilt Ingram Canc Ctr, Thorac Oncol Ctr, Nashville, TN USA.
   [Parkinson, David R.] Nodality Inc, San Francisco, CA USA.
   [Verweij, Jaap] Erasmus MC, Dept Med Oncol, Rotterdam, Netherlands.
   [Verweij, Jaap] Erasmus MC, Daniel den Hoed Canc Ctr, Rotterdam, Netherlands.
   [Hewitt, Stephen M.] NCI, Tissue Array Res Program, Pathol Lab, Adv Technol Ctr, Gaithersburg, MD USA.
   [Jessup, J. Milburn] NCI, Canc Diag Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
RP Jessup, JM (reprint author), NCI, Diagnost Evaluat Branch, Canc Diag Program, Div Canc Treatment & Diag, EPN 6040,6130 Execut Blvd, Rockville, MD 20892 USA.
EM jessupj@mail.nih.gov
OI Hewitt, Stephen/0000-0001-8283-1788
FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [U54 CA163069]
NR 52
TC 27
Z9 28
U1 3
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2012
VL 18
IS 6
BP 1515
EP 1523
DI 10.1158/1078-0432.CCR-11-2206
PG 9
WC Oncology
SC Oncology
GA 910VW
UT WOS:000301672400007
PM 22422403
ER

PT J
AU Hewitt, SM
   Badve, SS
   True, LD
AF Hewitt, Stephen M.
   Badve, Sunil S.
   True, Lawrence D.
TI Impact of Preanalytic Factors on the Design and Application of Integral
   Biomarkers for Directing Patient Therapy
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID PARAFFIN-EMBEDDED TISSUES; SURGICAL PATHOLOGY; CLINICAL-TRIALS;
   BREAST-CANCER; CHALLENGES; PROTEOMICS; PLASMA; RECOMMENDATIONS;
   SECTIONS; ANTIGEN
AB Molecular assays have been routinely applied to improve diagnosis for the last 25 years. Assays that guide therapy have a similar history; however, their evolution has lacked the focus on analytic integrity that is required for the molecularly targeted therapies of today. New molecularly targeted agents require assays of greater precision/quantitation to predict the likelihood of response, i.e., to identify patients whose tumors will respond, while at the same time excluding and protecting those patients whose tumors will not respond or in whom treatment will cause unacceptable toxicity. The handling of tissue has followed a fit-for-purpose approach focused on appropriateness for diagnostic needs, which is less rigorous than the demands of new molecular assays that interrogate DNA, RNA, and proteins in a quantitative, multiplex manner. There is a new appreciation of the importance and fragility of tissue specimens as the source of analytes to direct therapy. By applying a total test paradigm and defining and measuring sources of variability in specimens, we can develop a set of specifications that can be incorporated into the clinical-care environment to ensure that a specimen is appropriate for analysis and will return a true result. Clin Cancer Res; 18(6); 1524-30. (C)2012 AACR.
C1 [Hewitt, Stephen M.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Badve, Sunil S.] Indiana Univ, Hlth Pathol Lab, Indianapolis, IN 46204 USA.
   [True, Lawrence D.] Univ Washington, Med Ctr, Dept Pathol, Seattle, WA 98195 USA.
RP Hewitt, SM (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, MSC 4605, Bethesda, MD 20892 USA.
EM hewitts@mail.nih.gov
OI Hewitt, Stephen/0000-0001-8283-1788
FU Intramural NIH HHS [Z99 CA999999]
NR 29
TC 22
Z9 22
U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2012
VL 18
IS 6
BP 1524
EP 1530
DI 10.1158/1078-0432.CCR-11-2204
PG 7
WC Oncology
SC Oncology
GA 910VW
UT WOS:000301672400008
PM 22422404
ER

PT J
AU Williams, PM
   Lively, TG
   Jessup, JM
   Conley, BA
AF Williams, P. Michael
   Lively, Tracy G.
   Jessup, J. Milburn
   Conley, Barbara A.
TI Bridging the Gap: Moving Predictive and Prognostic Assays from Research
   to Clinical Use
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID GENOMIC REFERENCE MATERIALS; SURROGATE END-POINTS; AMERICAN-SOCIETY;
   DRUG DEVELOPMENT; BREAST-CANCER; TUMOR-MARKERS; MONOCLONAL-ANTIBODY;
   COLORECTAL-CANCER; METHOD VALIDATION; BIOMARKERS
AB The development of clinically useful molecular diagnostics requires validation of clinical assay performance and achievement of clinical qualification in clinical trials. As discussed elsewhere in this Focus section on molecular diagnostics, validation of assay performance must be rigorous, especially when the assay will be used to guide treatment decisions. Here we review some of the problems associated with assay development, especially for academic investigators. These include lack of expertise and resources for analytical validation, lack of experience in designing projects for a specific clinical use, lack of specimens from appropriate patient groups, and lack of access to Clinical Laboratory Improvement Amendments-certified laboratories. In addition, financial support for assay validation has lagged behind financial support for marker discovery or drug development, even though the molecular diagnostic may be considered necessary for the successful use of the companion therapeutic. The National Cancer Institute supports a large number of clinical trials and a significant effort in drug development. In order to address some of these barriers for predictive and prognostic assays that will be used in clinical trials to select patients for a particular treatment, stratify patients into molecularly defined subgroups, or choose between treatments for molecularly defined tumors, the National Cancer Institute has begun a pilot program designed to lessen barriers to the development of validated prognostic and predictive assays. Clin Cancer Res; 18(6); 1531-9. (C)2012 AACR.
C1 [Lively, Tracy G.; Jessup, J. Milburn; Conley, Barbara A.] NCI, Canc Diag Program, Div Canc Treatment & Diag, Rockville, MD 20892 USA.
   [Williams, P. Michael] Fairview Ctr, Mol Characterizat Clin Assay Dev Lab, Frederick, MD USA.
RP Conley, BA (reprint author), NCI, Canc Diag Program, Div Canc Treatment & Diag, EPN 6038,6130 Execut Blvd, Rockville, MD 20892 USA.
EM conleyba@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 54
TC 21
Z9 21
U1 0
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2012
VL 18
IS 6
BP 1531
EP 1539
DI 10.1158/1078-0432.CCR-11-2203
PG 9
WC Oncology
SC Oncology
GA 910VW
UT WOS:000301672400009
PM 22422405
ER

PT J
AU Schilsky, RL
   Doroshow, JH
   LeBlanc, M
   Conley, BA
AF Schilsky, Richard L.
   Doroshow, James H.
   LeBlanc, Michael
   Conley, Barbara A.
TI Development and Use of Integral Assays in Clinical Trials
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID LUNG-CANCER; DRUG DEVELOPMENT; PREDICTIVE BIOMARKERS; METHOD VALIDATION;
   DESIGN; ISSUES
AB Clinical trials that include integral biomarkers to determine eligibility, assign treatment, or assess outcome must employ robust assays to measure the molecular analyte of interest. The decision to develop a biomarker assay into a test suitable for use in humans should be driven by clinical need, that is, there should be a clear clinical purpose for undertaking the test development. Supporting in vitro or in vivo research on the ability of the marker to distinguish subgroups of patients with a given characteristic is necessary. The magnitude of the difference in treatment effect expected with use of the marker should be sufficient to support differential treatment prescription for marker-positive and -negative patients. Analytical and clinical validation of the marker assay should be completed before the clinical trial is initiated to ensure that the assay is stable enough for clinical use throughout the trial. Clinical use of the assay requires that it be performed in a Clinical Laboratory Improvement Amendments-accredited laboratory, and the need to apply for an Investigational Device Exemption from the U. S. Food and Drug Administration should be considered. In this article we elaborate on the steps required to get a biomarker assay ready for use as an integral component of a clinical trial and give an example of the use of an integral assay in a phase III trial. Clin Cancer Res; 18(6); 1540-6. (C)2012 AACR.
C1 [Doroshow, James H.; Conley, Barbara A.] NCI, Div Canc Treatment & Diag, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
   [Schilsky, Richard L.] Univ Chicago, Div Biol Sci, Hematol Oncol Sect, Chicago, IL 60637 USA.
   [Schilsky, Richard L.] Univ Chicago, Div Biol Sci, Ctr Comprehens Canc, Chicago, IL 60637 USA.
   [LeBlanc, Michael] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
RP Conley, BA (reprint author), NCI, Canc Diag Program, Div Canc Treatment & Diag, Dept Hlth & Human Serv, 6035A Execut Plaza N, Rockville, MD 20892 USA.
EM conleyba@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [P01 CA053996]
NR 19
TC 21
Z9 21
U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2012
VL 18
IS 6
BP 1540
EP 1546
DI 10.1158/1078-0432.CCR-11-2202
PG 7
WC Oncology
SC Oncology
GA 910VW
UT WOS:000301672400010
PM 22422406
ER

PT J
AU Meshinchi, S
   Hunger, SP
   Aplenc, R
   Adamson, PC
   Jessup, JM
AF Meshinchi, Soheil
   Hunger, Stephen P.
   Aplenc, Richard
   Adamson, Peter C.
   Jessup, J. Milburn
TI Lessons Learned from the Investigational Device Exemption Review of
   Children's Oncology Group Trial AAML1031
SO CLINICAL CANCER RESEARCH
LA English
DT Review
ID ACUTE MYELOID-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; STEM-CELL
   TRANSPLANTATION; CANCER GROUP; SORAFENIB; COMPLICATIONS; REGRESSION;
   REMISSION; PATIENT; DISEASE
AB The U.S. Food and Drug Administration is now exerting its regulatory authority over the use of molecular diagnostics and related assays for medical decision making in clinical trials, by performing pre-Investigational Device Exemption reviews in all phases of clinical trials. In this review, we assess the analytical performance of the assay for the diagnostic, and consider how that performance affects the diagnostic and the patient and their risks and benefits from treatment. We also discuss the process involved in the first review of a new Children's Oncology Group phase III trial in acute myelogenous leukemia. The lessons learned and recommendations for how to prepare for and incorporate this new level of regulatory review into the protocol development process are presented. Clin Cancer Res; 18(6); 1547-54. (C)2012 AACR.
C1 [Jessup, J. Milburn] NCI, Canc Diag Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
   [Meshinchi, Soheil] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
   [Hunger, Stephen P.] Childrens Hosp Colorado, Ctr Canc & Blood Disorders, Aurora, CO USA.
   [Hunger, Stephen P.] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO USA.
   [Aplenc, Richard; Adamson, Peter C.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
   [Aplenc, Richard] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
   [Jessup, J. Milburn] Childrens Oncol Grp, Arcadia, CA USA.
RP Jessup, JM (reprint author), NCI, Diagnost Evaluat Branch, Canc Diag Program, Div Canc Treatment & Diag, EPN 6040,6130 Execut Blvd, Rockville, MD 20892 USA.
EM jessupj@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [U10 CA098543]
NR 22
TC 9
Z9 9
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2012
VL 18
IS 6
BP 1547
EP 1554
DI 10.1158/1078-0432.CCR-11-2205
PG 8
WC Oncology
SC Oncology
GA 910VW
UT WOS:000301672400011
PM 22422407
ER

PT J
AU Chinnasamy, D
   Yu, ZY
   Kerkar, SP
   Zhang, L
   Morgan, RA
   Restifo, NP
   Rosenberg, SA
AF Chinnasamy, Dhanalakshmi
   Yu, Zhiya
   Kerkar, Sid P.
   Zhang, Ling
   Morgan, Richard A.
   Restifo, Nicholas P.
   Rosenberg, Steven A.
TI Local Delivery of Interleukin-12 Using T Cells Targeting VEGF Receptor-2
   Eradicates Multiple Vascularized Tumors in Mice
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID MYELOID SUPPRESSOR-CELLS; METASTATIC MELANOMA; ANTITUMOR-ACTIVITY;
   CARCINOMA PATIENTS; IL-12 TRIGGERS; GENE-THERAPY; ANGIOGENESIS; GROWTH;
   EXPRESSION; GLIOBLASTOMA
AB Purpose: We investigated the feasibility of delivering the proinflammatory cytokine interleukin (IL)-12 into tumor using T cells genetically engineered to express a chimeric antigen receptor (CAR) against the VEGF receptor-2 (VEGFR-2).
   Experimental Design: Two different strains of mice bearing five different established subcutaneous tumors were treated with syngeneic T cells cotransduced with an anti-VEGFR-2 CAR and a constitutively expressed single-chain murine IL-12 or an inducible IL-12 gene after host lymphodepletion. Tumor regression, survival of mice, and persistence of the transferred cells were evaluated.
   Results: Adoptive transfer of syngeneic T cells cotransduced with an anti-VEGFR-2 CAR and a constitutively expressing single-chain IL-12 resulted in the regression of five different established tumors of different histologies without the need for IL-2 administration. T cells transduced with either anti-VEGFR-2 CAR or single-chain IL-12 alone did not alter the tumor growth indicating that both of them had to be expressed in the same cell to mediate tumor regression. Anti-VEGFR-2 CAR and IL-12-cotransduced T cells infiltrated the tumors, expanded, and persisted for prolonged periods. The antitumor effect did not require the presence of host T and B cells but was dependent on host IL-12R-expressing cells. The anti-VEGFR-2 CAR changed the immunosuppressive tumor environment by altering/reducing both the systemic and the intratumoral CD11b(+)Gr1(+) myeloid suppressor cell subsets that expressed VEGFR-2.
   Conclusions: These results suggest that targeted delivery of IL-12 into the tumor environment with T cells redirected against VEGFR-2 is a promising approach for treating patients with a variety of solid tumor types. Clin Cancer Res; 18(6); 1672-83. (C)2012 AACR.
C1 [Chinnasamy, Dhanalakshmi; Yu, Zhiya; Kerkar, Sid P.; Zhang, Ling; Morgan, Richard A.; Restifo, Nicholas P.; Rosenberg, Steven A.] NCI, Surg Branch, Clin Res Ctr, Bethesda, MD 20892 USA.
RP Rosenberg, SA (reprint author), NCI, Surg Branch, Clin Res Ctr, Bldg 10-CRC,Room 3-3940,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA.
EM SAR@mail.nih.gov
RI Restifo, Nicholas/A-5713-2008; 
OI Restifo, Nicholas P./0000-0003-4229-4580
FU NIH; National Cancer Institute
FX This work was supported by the Intramural Research Program of the NIH,
   National Cancer Institute.
NR 50
TC 69
Z9 71
U1 2
U2 9
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2012
VL 18
IS 6
BP 1672
EP 1683
DI 10.1158/1078-0432.CCR-11-3050
PG 12
WC Oncology
SC Oncology
GA 910VW
UT WOS:000301672400024
PM 22291136
ER

PT J
AU Kummar, S
   Ji, JP
   Morgan, R
   Lenz, HJ
   Puhalla, SL
   Belani, CP
   Gandara, DR
   Allen, D
   Kiesel, B
   Beumer, JH
   Newman, EM
   Rubinstein, L
   Chen, A
   Zhang, YP
   Wang, LH
   Kinders, RJ
   Parchment, RE
   Tomaszewski, JE
   Doroshow, JH
AF Kummar, Shivaani
   Ji, Jiuping
   Morgan, Robert
   Lenz, Heinz-Josef
   Puhalla, Shannon L.
   Belani, Chandra P.
   Gandara, David R.
   Allen, Deborah
   Kiesel, Brian
   Beumer, Jan H.
   Newman, Edward M.
   Rubinstein, Larry
   Chen, Alice
   Zhang, Yiping
   Wang, Lihua
   Kinders, Robert J.
   Parchment, Ralph E.
   Tomaszewski, Joseph E.
   Doroshow, James H.
TI A Phase I Study of Veliparib in Combination with Metronomic
   Cyclophosphamide in Adults with Refractory Solid Tumors and Lymphomas
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID ADP-RIBOSE POLYMERASE; 0 CLINICAL-TRIAL; POLY(ADP-RIBOSE) POLYMERASE;
   ORAL CYCLOPHOSPHAMIDE; CANCER; INHIBITOR; CHEMOTHERAPY; GAMMA-H2AX;
   ABT-888; CELLS
AB Purpose: Oral administration of the alkylating agent cyclophosphamide at low doses, metronomic dosing, is well tolerated, with efficacy in multiple tumor types. PARP inhibition potentiates effects of cyclophosphamide in preclinical models. We conducted a phase I trial of the PARP inhibitor veliparib and metronomic cyclophosphamide in patients with refractory solid tumors and lymphoid malignancies.
   Experimental Design: Objectives were to establish the safety and maximum tolerated dose (MTD) of the combination; characterize veliparib pharmacokinetics (PK); measure poly(ADP-ribose) (PAR), a product of PARP, in tumor biopsies and peripheral blood mononuclear cells (PBMC); and measure the DNA-damage marker gamma H2AX in PBMCs and circulating tumor cells (CTC). Cyclophosphamide was administered once daily in 21-day cycles in combination with veliparib administered once daily for 7, 14, or 21 days.
   Results: Thirty-five patients were enrolled. The study treatment was well tolerated, and the MTD was established as veliparib 60 mg with cyclophosphamide 50 mg given once daily. Seven patients had partial responses; an additional six patients had disease stabilization for at least six cycles. PAR was significantly decreased in PBMCs (by at least 50%) and tumor biopsies (by at least 80%) across dose levels (DL); gamma H2AX levels were increased in CTCs from seven of nine patients evaluated after drug administration.
   Conclusions: The combination of veliparib with metronomic cyclophosphamide is well tolerated and shows promising activity in a subset of patients with BRCA mutations. A phase II trial of the combination compared with single-agent cyclophosphamide is ongoing in BRCA-positive ovarian cancer, triple-negative breast cancer, and low-grade lymphoma. Clin Cancer Res; 18(6); 1726-34. (C) 2012 AACR.
C1 [Doroshow, James H.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Kummar, Shivaani; Rubinstein, Larry; Chen, Alice; Tomaszewski, Joseph E.; Doroshow, James H.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
   [Ji, Jiuping; Zhang, Yiping; Wang, Lihua; Kinders, Robert J.; Parchment, Ralph E.] NCI, Appl Dev Res Support Directorate, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21701 USA.
   [Morgan, Robert; Newman, Edward M.] City Hope Comprehens Canc Ctr, Duarte, CA USA.
   [Lenz, Heinz-Josef] USC Norris Comprehens Canc Ctr, Los Angeles, CA USA.
   [Gandara, David R.] Univ Calif Davis, Ctr Canc, Sacramento, CA 95817 USA.
   [Puhalla, Shannon L.; Kiesel, Brian; Beumer, Jan H.] Univ Pittsburgh, Canc Inst, Mol Therapeut Drug Discovery Program, Pittsburgh, PA USA.
   [Beumer, Jan H.] Univ Pittsburgh, Sch Pharm, Pittsburgh, PA USA.
   [Belani, Chandra P.] Penn State Coll Med, Hershey, PA USA.
RP Doroshow, JH (reprint author), NCI, Ctr Canc Res, NIH, Bldg 31,Room 3A44,31 Ctr Dr, Bethesda, MD 20892 USA.
EM doroshoj@mail.nih.gov
OI Belani, Chandra/0000-0001-5049-5329; Beumer, Jan/0000-0002-8978-9401
FU NCI [U01-CA062505, U01-CA099168, P30-CA47904]; NIH [HHSN261200800001E];
   Center for Cancer Research
FX This work has been supported in whole or in part with federal funds from
   the NCI, NIH, under contract no. HHSN261200800001E and in part by the
   Intramural Research Program of the NIH, NCI, Center for Cancer Research.
   Additional support was provided by NCI, Cancer Therapy Evaluation
   Program cooperative agreements U01-CA062505 and U01-CA099168 and NCI
   grant P30-CA47904.
NR 32
TC 85
Z9 86
U1 0
U2 9
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2012
VL 18
IS 6
BP 1726
EP 1734
DI 10.1158/1078-0432.CCR-11-2821
PG 9
WC Oncology
SC Oncology
GA 910VW
UT WOS:000301672400029
PM 22307137
ER

PT J
AU Wacholder, S
   Yeager, M
   Liao, LM
AF Wacholder, Sholom
   Yeager, Meredith
   Liao, Linda M.
TI Invited Commentary: More Surprises From a Gene Desert
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Editorial Material
DE neoplasms; chromosomes; human; pair 8; diabetes mellitus; DNA;
   intergenic; genetic pleiotropy; mortality
ID GENOME-WIDE ASSOCIATION; CHROMOSOME 8Q24; PROSTATE-CANCER; FALSE
   DISCOVERY; BLADDER-CANCER; RISK; LOCUS; EPIDEMIOLOGY; PROBABILITY;
   VARIANTS
AB Pleiotropy across the 8q24 region is perhaps the most intriguing of the genome-wide association findings relating to cancer. This region of chromosome 8 is a gene desert, far from any recognized genes. Guarrera et al., whose work is reported in this issue (Am J Epidemiol. 2012;175(6):479-487), took an epidemiologic approach to learn more about the 8q24 region. They capitalized on their ascertainment of other endpoints in members of the cohort at the Turin site of the European Prospective Investigation Into Cancer and Nutrition to investigate multiple outcomes for additional pleiotropic effects in the 8q24 region. Alternative design options might involve genotyping of more variants, incorporation of more cases, or use of a single control group close to the size of the most common case group. Their analytic methods reflect the uncertainty of the underlying biology. The findings sharpen the scientific question about how variation in the 8q24 region affects pathogenesis. The genome-wide association effort is possible because of the economy of scale afforded by extremely dense genotyping. Strict adherence to the hypothesis-driven approach would ignore information that is obtainable at a trivial cost. The genome-wide association strategy tests whether agnostic data-mining methods can advance knowledge alongside or even in place of the standard hypothesis-driven approach, which is the conventional scientific method children learn in kindergarten and onward, even through graduate school and beyond.
C1 [Wacholder, Sholom] Natl Canc Ctr, Div Canc Epidemiol & Genet, Biostat Branch, Bethesda, MD USA.
   [Liao, Linda M.] Natl Canc Inst, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, Bethesda, MD USA.
   [Yeager, Meredith] Natl Canc Inst, SAIC, Frederick, MD USA.
RP Wacholder, S (reprint author), Natl Canc Inst, Natl Inst Hlth, Execut Plaza S,6120 Execut Blvd,Suite 5050,MSC 72, Rockville, MD 20852 USA.
EM wacholds@mail.nih.gov
RI perumal, murugiah/D-1565-2012; 
OI Liao, Linda/0000-0002-1923-5294
FU Intramural NIH HHS
NR 29
TC 2
Z9 2
U1 0
U2 4
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 MAR 15
PY 2012
VL 175
IS 6
BP 488
EP 491
DI 10.1093/aje/kwr429
PG 4
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 910XJ
UT WOS:000301681600002
PM 22350582
ER

PT J
AU Dasharathy, SS
   Mumford, SL
   Pollack, AZ
   Perkins, NJ
   Mattison, DR
   Wactawski-Wende, J
   Schisterman, EF
AF Dasharathy, Sonya S.
   Mumford, Sunni L.
   Pollack, Anna Z.
   Perkins, Neil J.
   Mattison, Donald R.
   Wactawski-Wende, Jean
   Schisterman, Enrique F.
TI Menstrual Bleeding Patterns Among Regularly Menstruating Women
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE anovulation; bleeding patterns; menstrual blood loss; metrorrhagia;
   reproductive hormones
ID MARGINAL STRUCTURAL MODELS; LATE-REPRODUCTIVE AGE; BREAST-CANCER;
   MENOPAUSAL TRANSITION; CYCLE CHARACTERISTICS; PHYSICAL-ACTIVITY;
   OVARIAN-CANCER; RISK; FERTILITY; IRREGULARITY
AB Menstrual bleeding patterns are considered relevant indicators of reproductive health, though few studies have evaluated patterns among regularly menstruating premenopausal women. The authors evaluated self-reported bleeding patterns, incidence of spotting, and associations with reproductive hormones among 201 women in the BioCycle Study (2005-2007) with 2 consecutive cycles. Bleeding patterns were assessed by using daily questionnaires and pictograms. Marginal structural models were used to evaluate associations between endogenous hormone concentrations and subsequent total reported blood loss and bleeding length by weighted linear mixed-effects models and weighted parametric survival analysis models. Women bled for a median of 5 days (standard deviation: 1.5) during menstruation, with heavier bleeding during the first 3 days. Only 4.8% of women experienced midcycle bleeding. Increased levels of follicle-stimulating hormone (beta = 0.20, 95% confidence interval: 0.13, 0.27) and progesterone (beta = 0.06, 95% confidence interval: 0.03, 0.09) throughout the cycle were associated with heavier menstrual bleeding, and higher follicle-stimulating hormone levels were associated with longer menses. Bleeding duration and volume were reduced after anovulatory compared with ovulatory cycles (geometric mean blood loss: 29.6 vs. 47.2 mL; P = 0.07). Study findings suggest that detailed characterizations of bleeding patterns may provide more insight than previously thought as noninvasive markers for endocrine status in a given cycle.
C1 [Dasharathy, Sonya S.; Mumford, Sunni L.; Pollack, Anna Z.; Perkins, Neil J.; Mattison, Donald R.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD 20852 USA.
   [Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
RP Schisterman, EF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA.
EM schistee@mail.nih.gov
RI Mattison, Donald/L-4661-2013; 
OI Mattison, Donald/0000-0001-5623-0874; 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 40
TC 19
Z9 22
U1 1
U2 10
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD MAR 15
PY 2012
VL 175
IS 6
BP 536
EP 545
DI 10.1093/aje/kwr356
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 910XJ
UT WOS:000301681600008
PM 22350580
ER

PT J
AU Blackstone, C
   Murphy, CT
AF Blackstone, Craig
   Murphy, Coleen T.
TI Cell biology of disease and aging: a two-way street
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Editorial Material
C1 [Blackstone, Craig] Natl Inst Neurol Disorders & Stroke, Neurogenet Branch, NIH, Bethesda, MD 20892 USA.
   [Murphy, Coleen T.] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA.
   [Murphy, Coleen T.] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
RP Blackstone, C (reprint author), Natl Inst Neurol Disorders & Stroke, Neurogenet Branch, NIH, Bethesda, MD 20892 USA.
EM blackstc@ninds.nih.gov; ctmurphy@princeton.edu
NR 0
TC 0
Z9 0
U1 0
U2 3
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD MAR 15
PY 2012
VL 23
IS 6
BP 975
EP 975
DI 10.1091/mbc.E11-12-0985
PG 1
WC Cell Biology
SC Cell Biology
GA 907XO
UT WOS:000301453700011
ER

PT J
AU Cohen-Fix, O
   Shav-Tal, Y
AF Cohen-Fix, Orna
   Shav-Tal, Yaron
TI Nuclear biology: making sense of complex processes
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Editorial Material
C1 [Cohen-Fix, Orna] NIDDK, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
   [Shav-Tal, Yaron] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, IL-52900 Ramat Gan, Israel.
   [Shav-Tal, Yaron] Bar Ilan Univ, Inst Nanotechnol, IL-52900 Ramat Gan, Israel.
RP Cohen-Fix, O (reprint author), NIDDK, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
EM ornacf@helix.nih.gov; Yaron.Shav-Tal@biu.ac.il
NR 2
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD MAR 15
PY 2012
VL 23
IS 6
BP 976
EP 976
DI 10.1091/mbc.E11-12-0981
PG 1
WC Cell Biology
SC Cell Biology
GA 907XO
UT WOS:000301453700012
ER

PT J
AU Altan-Bonnet, N
   Steele-Mortimer, O
AF Altan-Bonnet, Nihal
   Steele-Mortimer, Olivia
TI Cell-pathogen interactions (viruses and bacteria)
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Editorial Material
C1 [Altan-Bonnet, Nihal] Rutgers State Univ, Host Pathogen Dynam Grp, Dept Biol Sci, Newark, NJ 07102 USA.
   [Steele-Mortimer, Olivia] NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP Altan-Bonnet, N (reprint author), Rutgers State Univ, Host Pathogen Dynam Grp, Dept Biol Sci, Newark, NJ 07102 USA.
EM nabonnet@andromeda.rutgers.edu
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD MAR 15
PY 2012
VL 23
IS 6
BP 978
EP 978
DI 10.1091/mbc.E11-12-0980
PG 1
WC Cell Biology
SC Cell Biology
GA 907XO
UT WOS:000301453700014
ER

PT J
AU Reed, JL
   Scott, DE
   Bray, M
AF Reed, Jennifer L.
   Scott, Dorothy E.
   Bray, Mike
TI Eczema Vaccinatum
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Review
ID ATOPIC-DERMATITIS; SMALLPOX VACCINATION; SKIN INFLAMMATION; PROGRESSIVE
   VACCINIA; UNITED-STATES; MOUSE MODEL; VIRUS; DISEASE; COMPLICATIONS;
   CELLS
AB Eczema vaccinatum (EV) is a complication of smallpox vaccination that can occur in persons with eczema/atopic dermatitis (AD), in which vaccinia virus disseminates to cause an extensive rash and systemic illness. Because persons with eczema are deferred from vaccination, only a single, accidentally transmitted case of EV has been described in the medical literature since military vaccination was resumed in the United States in 2002. To enhance understanding of EV, we review its history during the era of universal vaccination and discuss its relationship to complications in persons with other diseases or injuries of the skin. We then discuss current concepts of the pathophysiology of AD, noting how defective skin barrier function, epidermal hyperplasia, and abnormal immune responses favor the spread of poxviral infection, and identify a number of unanswered questions about EV. We conclude by considering how its occurrence might be minimized in the event of a return to universal vaccination.
C1 [Reed, Jennifer L.; Scott, Dorothy E.] US FDA, Lab Plasma Derivat, Ctr Biol Evaluat & Res, Rockville, MD 20892 USA.
   [Bray, Mike] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA.
RP Reed, JL (reprint author), US FDA, Lab Plasma Derivat, Ctr Biol Evaluat & Res, 8800 Rockville Pike,HFM 345,NIH Bldg 29,Rm 302, Rockville, MD 20892 USA.
EM jennifer.reed@fda.hhs.gov
FU Food and Drug Administration, Center for Biologics Evaluation and
   Research
FX This work is supported by the Food and Drug Administration, Center for
   Biologics Evaluation and Research operating funds. These findings and
   conclusions have not been formally disseminated by the Food and Drug
   Administration and should not be construed to represent any Agency
   determination or policy.
NR 59
TC 17
Z9 17
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD MAR 15
PY 2012
VL 54
IS 6
BP 832
EP 840
DI 10.1093/cid/cir952
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 899CK
UT WOS:000300790900017
PM 22291103
ER

PT J
AU Muller, JR
   Waldmann, TA
   Dubois, S
AF Mueller, Juergen R.
   Waldmann, Thomas A.
   Dubois, Sigrid
TI Selective Dependence of H2-M3-Restricted CD8 Responses on IL-15
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID NATURAL-KILLER-CELLS; MARROW-DERIVED CELLS; MEMORY T-CELLS; CUTTING
   EDGE; VIRUS; INTERLEUKIN-15; PROLIFERATION; IL-15R-ALPHA; MICE; NK
AB We studied whether CD8 T cell responses that are mediated by unconventional MHC class Ib molecules are IL-15 dependent in mice. CD8(+) T cell responses to Listeria monocytogenes infection that are restricted by the MHC class Ib molecule H2-M3 decreased in the absence of IL-15, whereas other primary MHC class Ib- and MHC class Ia-restricted responses were IL-15 independent. This result was confirmed in MHC class Ia-deficient mice in which IL-15 deficiency also reduced H2-M3-restricted but not all CD8 T cell responses to L. monocytogenes. IL-15 deficiency did not affect proliferation or survival of responding H2-M3-restricted CD8(+) T cells, but IL-15 was necessary to detect H2-M3-restricted CD8(+) T cells in naive mice. This finding suggests that these CD8(+) T cells require IL-15 during development, but become IL-15 independent after activation. IL-15 was necessary for the survival of most class Ib-restricted CD8(+) T cells, starting at the mature thymocyte stage in naive mice, but does not affect a distinct CD44(low)/CD122(low) subpopulation. These data suggest that the nature of the selecting MHC class Ib molecule determines whether CD8(+) T cells acquire IL-15 dependence during thymic development. The Journal of Immunology, 2012, 188: 2575-2582.
C1 [Mueller, Juergen R.; Waldmann, Thomas A.; Dubois, Sigrid] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Dubois, S (reprint author), NCI, Metab Branch, Ctr Canc Res, NIH, Bldg 10,Room 4B47,10 Ctr Dr, Bethesda, MD 20892 USA.
EM duboiss@mail.nih.gov
FU National Cancer Institute at the National Institutes of Health
FX This work was supported by the intramural research program of the
   National Cancer Institute at the National Institutes of Health.
NR 33
TC 1
Z9 1
U1 1
U2 3
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAR 15
PY 2012
VL 188
IS 6
BP 2575
EP 2582
DI 10.4049/jimmunol.1102393
PG 8
WC Immunology
SC Immunology
GA 903OD
UT WOS:000301126000013
PM 22312130
ER

PT J
AU Horka, H
   Staudt, V
   Klein, M
   Taube, C
   Reuter, S
   Dehzad, N
   Andersen, JF
   Kopecky, J
   Schild, H
   Kotsyfakis, M
   Hoffmann, M
   Gerlitzki, B
   Stassen, M
   Bopp, T
   Schmitt, E
AF Horka, Helena
   Staudt, Valerie
   Klein, Matthias
   Taube, Christian
   Reuter, Sebastian
   Dehzad, Nina
   Andersen, John F.
   Kopecky, Jan
   Schild, Hansjoerg
   Kotsyfakis, Michalis
   Hoffmann, Markus
   Gerlitzki, Bastian
   Stassen, Michael
   Bopp, Tobias
   Schmitt, Edgar
TI The Tick Salivary Protein Sialostatin L Inhibits the Th9-Derived
   Production of the Asthma-Promoting Cytokine IL-9 and Is Effective in the
   Prevention of Experimental Asthma
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CELL-MEDIATED SUPPRESSION; CD4(+) T-CELLS; IXODES-SCAPULARIS; AIRWAY
   INFLAMMATION; EPITHELIAL-CELLS; TGF-BETA; INTERLEUKIN 9; EXPRESSION;
   ANTIBODY; DISEASE
AB Ticks developed a multitude of different immune evasion strategies to obtain a blood meal. Sialostatin L is an immunosuppressive cysteine protease inhibitor present in the saliva of the hard tick Ixodes scapularis. In this study, we demonstrate that sialostatin L strongly inhibits the production of IL-9 by Th9 cells. Because we could show recently that Th9-derived IL-9 is essentially involved in the induction of asthma symptoms, sialostatin L was used for the treatment of experimental asthma. Application of sialostatin L in a model of experimental asthma almost completely abrogated airway hyperresponsiveness and eosinophilia. Our data suggest that sialostatin L can prevent experimental asthma, most likely by inhibiting the IL-9 production of Th9 cells. Thus, alternative to IL-9 neutralization sialostatin L provides the basis for the development of innovative therapeutic strategies to treat asthma. The Journal of Immunology, 2012, 188: 2669-2676.
C1 [Staudt, Valerie; Klein, Matthias; Schild, Hansjoerg; Hoffmann, Markus; Gerlitzki, Bastian; Stassen, Michael; Bopp, Tobias; Schmitt, Edgar] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Immunol, D-55131 Mainz, Germany.
   [Horka, Helena; Kopecky, Jan; Kotsyfakis, Michalis] Univ S Bohemia, Inst Parasitol, Ctr Biol, Acad Sci Czech Republ, Ceske Budejovice 37005, Czech Republic.
   [Horka, Helena; Kopecky, Jan; Kotsyfakis, Michalis] Univ S Bohemia, Fac Sci, Ceske Budejovice 37005, Czech Republic.
   [Taube, Christian] Leiden Univ, Dept Pulmonol, Med Ctr, NL-2333 ZA Leiden, Netherlands.
   [Reuter, Sebastian; Dehzad, Nina] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Med Clin 3, D-55131 Mainz, Germany.
   [Andersen, John F.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
RP Bopp, T (reprint author), Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Immunol, Bldg 708,Langenbeckstr 1, D-55131 Mainz, Germany.
EM boppt@uni-mainz.de; eschmitt@uni-mainz.de
RI Reuter, Sebastian/L-1804-2013; Langhansova, Helena /G-9292-2014;
   Kotsyfakis, Michail/G-9525-2014; Kopecky, Jan/G-9347-2014
OI Kotsyfakis, Michail/0000-0002-7526-1876; 
FU Deutsche Forschungsgemeinschaft [SFB TR52 TPA1, SCHM 1014/5-1]; DFG
   [Graduiertenkolleg 1043]; "Forschungszentrum Immunologie" of the
   University Medical Center; Asthma Core Facility; Johannes Gutenberg
   University Mainz; Grant Agency of the Czech Republic [P302/11/ J029];
   Research Center of the Ministry of Education, Youth, and Sports of the
   Czech Republic [LC06009]
FX This work was supported by Deutsche Forschungsgemeinschaft Grants SFB
   TR52 TPA1 (to M. Klein, T. B., and E. S.) and SCHM 1014/5-1 (to V. S.,
   T. B., and E. S.); DFG-Graduiertenkolleg 1043: International Graduate
   School of Immunotherapy (to E. S. and T. B.); "Forschungszentrum
   Immunologie" of the University Medical Center (to E. S. and T. B.); the
   Asthma Core Facility (to C. T.); Johannes Gutenberg University Mainz;
   Grant Agency of the Czech Republic Bilateral Grant P302/11/ J029 (to H.
   H., M. Klein, and J.K.); and Research Center of the Ministry of
   Education, Youth, and Sports of the Czech Republic Grant LC06009 (to H.
   H. and J.K.).
NR 42
TC 23
Z9 25
U1 1
U2 10
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAR 15
PY 2012
VL 188
IS 6
BP 2669
EP 2676
DI 10.4049/jimmunol.1100529
PG 8
WC Immunology
SC Immunology
GA 903OD
UT WOS:000301126000022
PM 22327077
ER

PT J
AU Leelahavanichkul, A
   Bocharov, AV
   Kurlander, R
   Baranova, IN
   Vishnyakova, TG
   Souza, ACP
   Hu, XZ
   Doi, K
   Vaisman, B
   Amar, M
   Sviridov, D
   Chen, ZG
   Remaley, AT
   Csako, G
   Patterson, AP
   Yuen, PST
   Star, RA
   Eggerman, TL
AF Leelahavanichkul, Asada
   Bocharov, Alexander V.
   Kurlander, Roger
   Baranova, Irina N.
   Vishnyakova, Tatyana G.
   Souza, Ana C. P.
   Hu, Xuzhen
   Doi, Kent
   Vaisman, Boris
   Amar, Marcelo
   Sviridov, Denis
   Chen, Zhigang
   Remaley, Alan T.
   Csako, Gyorgy
   Patterson, Amy P.
   Yuen, Peter S. T.
   Star, Robert A.
   Eggerman, Thomas L.
TI Class B Scavenger Receptor Types I and II and CD36 Targeting Improves
   Sepsis Survival and Acute Outcomes in Mice
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID ACUTE KIDNEY INJURY; ACUTE-RENAL-FAILURE; TOLL-LIKE RECEPTORS;
   APOLIPOPROTEIN-A-I; GLUCOCORTICOID PRODUCTION; INFLAMMATORY RESPONSES;
   BACTERIAL RECOGNITION; SIGNALING CASCADE; MIMETIC PEPTIDE; UNITED-STATES
AB Class B scavenger receptors (SR-Bs), such as SR-BI/II or CD36, bind lipoproteins but also mediate bacterial recognition and phagocytosis. In evaluating whether blocking receptors can prevent intracellular bacterial proliferation, phagocyte cytotoxicity, and proinflammatory signaling in bacterial infection/sepsis, we found that SR-BI/II- or CD36-deficient phagocytes are characterized by a reduced intracellular bacterial survival and a lower cytokine response and were protected from bacterial cytotoxicity in the presence of antibiotics. Mice deficient in either SR-BI/II or CD36 are protected from antibiotic-treated cecal ligation and puncture (CLP)-induced sepsis, with greatly increased peritoneal granulocytic phagocyte survival (8-fold), a drastic diminution in peritoneal bacteria counts, and a 50-70% reduction in systemic inflammation (serum levels of IL-6, TNF-a, and IL-10) and organ damage relative to CLP in wild-type mice. The survival rate of CD36-deficient mice after CLP was 58% compared with 17% in control mice. When compensated for mineralocorticoid and glucocorticoid deficiency, SR-BI/II-deficient mice had nearly a 50% survival rate versus 5% in mineralo-/glucocorticoid-treated controls. Targeting SR-B receptors with L-37pA, a peptide that functions as an antagonist of SR-BI/II and CD36 receptors, also increased peritoneal granulocyte counts, as well as reduced peritoneal bacteria and bacterium-induced cytokine secretion. In the CLP mouse sepsis model, L-37pA improved survival from 6 to 27%, reduced multiple organ damage, and improved kidney function. These results demonstrate that the reduction of both SR-BI/II- and CD36-dependent bacterial invasion and inflammatory response in the presence of antibiotic treatment results in granulocyte survival and local bacterial containment, as well as reduces systemic inflammation and organ damage and improves animal survival during severe infections. The Journal of Immunology, 2012, 188: 2749-2758.
C1 [Bocharov, Alexander V.; Kurlander, Roger; Baranova, Irina N.; Vishnyakova, Tatyana G.; Chen, Zhigang; Csako, Gyorgy; Patterson, Amy P.; Eggerman, Thomas L.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
   [Leelahavanichkul, Asada; Souza, Ana C. P.; Hu, Xuzhen; Doi, Kent; Yuen, Peter S. T.; Star, Robert A.] NIDDK, Renal Diagnost & Therapeut Unit, NIH, Bethesda, MD 20892 USA.
   [Leelahavanichkul, Asada] Chulalongkorn Univ, Fac Med, Dept Microbiol, Bangkok 10330, Thailand.
   [Vaisman, Boris; Amar, Marcelo; Sviridov, Denis; Remaley, Alan T.] NHLBI, NIH, Bethesda, MD 20892 USA.
   [Patterson, Amy P.] NIH, Off Biotechnol Activ, Off Director, Bethesda, MD 20892 USA.
   [Eggerman, Thomas L.] NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD 20892 USA.
RP Bocharov, AV (reprint author), NIH, Dept Lab Med, Ctr Clin, Bldg 9,Room 1N128,8800 Rockville Pike, Bethesda, MD 20892 USA.
EM abocharov@cc.nih.gov
RI Yuen, Peter/B-1954-2008
OI Yuen, Peter/0000-0001-9557-3909
FU National Institutes of Health; National Institute of Diabetes and
   Digestive and Kidney Diseases; Clinical Center; National Heart, Lung,
   and Blood Institute; National Institute of Allergy and Infectious
   Diseases
FX This work was supported by the National Institutes of Health Intramural
   Research Programs, including support from the National Institute of
   Diabetes and Digestive and Kidney Diseases; the Clinical Center; the
   National Heart, Lung, and Blood Institute; and the National Institute of
   Allergy and Infectious Diseases.
NR 51
TC 21
Z9 22
U1 0
U2 5
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAR 15
PY 2012
VL 188
IS 6
BP 2749
EP 2758
DI 10.4049/jimmunol.1003445
PG 10
WC Immunology
SC Immunology
GA 903OD
UT WOS:000301126000031
PM 22327076
ER

PT J
AU De Arras, L
   Yang, IV
   Lackford, B
   Riches, DWH
   Prekeris, R
   Freedman, JH
   Schwartz, DA
   Alper, S
AF De Arras, Lesly
   Yang, Ivana V.
   Lackford, Brad
   Riches, David W. H.
   Prekeris, Rytis
   Freedman, Jonathan H.
   Schwartz, David A.
   Alper, Scott
TI Spatiotemporal Inhibition of Innate Immunity Signaling by the Tbc1d23
   RAB-GAP
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID TOLL-LIKE RECEPTORS; NF-KAPPA-B; UNFOLDED PROTEIN RESPONSE;
   PATTERN-RECOGNITION RECEPTORS; ENDOPLASMIC-RETICULUM STRESS; XBP1
   MESSENGER-RNA; IFN-BETA INDUCTION; TRANSCRIPTION FACTOR; ACTIVATION;
   MACROPHAGES
AB We previously identified Tbc1d23 as a candidate novel regulator of innate immunity using comparative genomics RNA interference screens in Caenorhabditis elegans and mouse macrophages. Using Tbc1d23 knockout mice and macrophages engineered to overexpress Tbc1d23, we now show that Tbc1d23 is a general inhibitor of innate immunity signaling, strongly inhibiting multiple TLR and dectin-signaling pathways. Tbc1d23 likely acts downstream of the TLR-signaling adaptors MyD88 and Trif and upstream of the transcription factor XBP1. Importantly, like XBP1, Tbc1d23 affects the maintenance, but not the initiation, of inflammatory cytokine production induced by LPS. Tbc1d23 acts as a RAB-GAP to regulate innate immunity signaling. Thus, Tbc1d23 exerts its inhibitory effect on innate immunity signaling in a spatiotemporal fashion. The identification of a novel spatiotemporal regulator of innate immunity signaling validates the comparative genomics approach for innate immunity gene discovery. The Journal of Immunology, 2012, 188: 2905-2913.
C1 [De Arras, Lesly; Riches, David W. H.; Alper, Scott] Natl Jewish Hlth, Integrated Dept Immunol, Denver, CO 80206 USA.
   [De Arras, Lesly; Riches, David W. H.; Alper, Scott] Univ Colorado, Denver, CO 80206 USA.
   [De Arras, Lesly; Yang, Ivana V.; Schwartz, David A.; Alper, Scott] Natl Jewish Hlth, Ctr Genes Environm & Hlth, Denver, CO 80206 USA.
   [Yang, Ivana V.; Riches, David W. H.; Schwartz, David A.] Univ Colorado, Dept Med, Aurora, CO 80045 USA.
   [Lackford, Brad] Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, NIH, Durham, NC 27709 USA.
   [Riches, David W. H.] Natl Jewish Hlth, Cell Biol Program, Dept Pediat, Denver, CO 80206 USA.
   [Prekeris, Rytis] Univ Colorado, Dept Cell & Dev Biol, Aurora, CO 80045 USA.
   [Freedman, Jonathan H.] Natl Inst Environm Hlth Sci, Lab Toxicol & Pharmacol, NIH, Durham, NC 27709 USA.
RP Alper, S (reprint author), Natl Jewish Hlth, Integrated Dept Immunol, 1400 Jackson St, Denver, CO 80206 USA.
EM alpers@njhealth.org
FU National Institute of Environmental Health Sciences [R21ES019256,
   Z01ES102045, Z01ES101946]; National Heart Lung and Blood Institute
FX This work was supported by R21ES019256 from the National Institute of
   Environmental Health Sciences and the Intramural Research Programs of
   the National Heart Lung and Blood Institute and the National Institute
   of Environmental Health Sciences (Z01ES102045 and Z01ES101946).
NR 60
TC 7
Z9 7
U1 2
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 MAR 15
PY 2012
VL 188
IS 6
BP 2905
EP 2913
DI 10.4049/jimmunol.1102595
PG 9
WC Immunology
SC Immunology
GA 903OD
UT WOS:000301126000046
PM 22312129
ER

PT J
AU Insel, TR
   Sahakian, BJ
AF Insel, Thomas R.
   Sahakian, Barbara J.
TI A plan for mental illness
SO NATURE
LA English
DT Editorial Material
ID HEALTH
C1 [Insel, Thomas R.] NIMH, NIH, Bethesda, MD 20892 USA.
   [Sahakian, Barbara J.] Univ Cambridge, Dept Psychiat, Cambridge CB2 1TN, England.
   [Sahakian, Barbara J.] Univ Cambridge, MRC Wellcome Trust Behav & Clin Neurosci Inst, Cambridge CB2 1TN, England.
RP Insel, TR (reprint author), NIMH, NIH, Bethesda, MD 20892 USA.
EM bjs1001@cam.ac.uk
RI Nye, Jeffrey/G-6520-2012
OI Nye, Jeffrey/0000-0002-6056-281X
NR 10
TC 37
Z9 38
U1 2
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD MAR 15
PY 2012
VL 483
IS 7389
BP 269
EP 269
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 908HP
UT WOS:000301481800023
PM 22422245
ER

PT J
AU Koralek, AC
   Jin, X
   Ii, JDL
   Costa, RM
   Carmena, JM
AF Koralek, Aaron C.
   Jin, Xin
   Ii, John D. Long
   Costa, Rui M.
   Carmena, Jose M.
TI Corticostriatal plasticity is necessary for learning intentional
   neuroprosthetic skills
SO NATURE
LA English
DT Article
ID COGNITIVE SKILL; PREFRONTAL CORTEX; STRIATAL NEURONS; MOTOR CORTEX;
   ACQUISITION; CONSOLIDATION; PERFORMANCE; CONTINGENCY; ACTIVATION;
   NETWORKS
AB The ability to learn new skills and perfect them with practice applies not only to physical skills but also to abstract skills(1), like motor planning or neuroprosthetic actions. Although plasticity in corticostriatal circuits has been implicated in learning physical skills(2-4), it remains unclear if similar circuits or processes are required for abstract skill learning. Here we use a novel behavioural task in rodents to investigate the role of corticostriatal plasticity in abstract skill learning. Rodents learned to control the pitch of an auditory cursor to reach one of two targets by modulating activity in primary motor cortex irrespective of physical movement. Degradation of the relation between action and outcome, as well as sensory-specific devaluation and omission tests, demonstrate that these learned neuroprosthetic actions are intentional and goal-directed, rather than habitual. Striatal neurons change their activity with learning, with more neurons modulating their activity in relation to target-reaching as learning progresses. Concomitantly, strong relations between the activity of neurons in motor cortex and the striatum emerge. Specific deletion of striatal NMDA receptors impairs the development of this corticostriatal plasticity, and disrupts the ability to learn neuroprosthetic skills. These results suggest that corticostriatal plasticity is necessary for abstract skill learning, and that neuroprosthetic movements capitalize on the neural circuitry involved in natural motor learning.
C1 [Jin, Xin; Costa, Rui M.] NIAAA, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA.
   [Koralek, Aaron C.; Ii, John D. Long; Carmena, Jose M.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA.
   [Carmena, Jose M.] Univ Calif Berkeley, Dept Elect Engn & Comp Sci, Berkeley, CA 94720 USA.
   [Carmena, Jose M.] Univ Calif Berkeley, Program Cognit Sci, Berkeley, CA 94720 USA.
   [Carmena, Jose M.] Univ Calif Berkeley, UC Berkeley & UC San Francisco Joint Grad Grp Bio, Berkeley, CA 94720 USA.
   [Costa, Rui M.] Champalimaud Ctr Unknown, Champalimaud Neurosci Programme, P-1400038 Lisbon, Portugal.
RP Costa, RM (reprint author), NIAAA, Lab Integrat Neurosci, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA.
EM ruicosta@fchampalimaud.org; carmena@eecs.berkeley.edu
OI Koralek, Aaron/0000-0001-5205-0171; Costa, Rui/0000-0003-0495-8374
FU National Science Foundation [0954243]; Multiscale Systems Research
   Center; Defense Advanced Research Projects Agency [N66001-10-C-2008];
   Division of Intramural Clinical and Basic Research of the National
   Institute on Alcohol Abuse and Alcoholism [239527]; European Research
   Council [STG 243393]
FX We thank S. Venkatraman for the three-axis accelerometer, Y. Li for the
   RGS9L-Cre mice, K. Nakazawa for the NMDAR1-loxP mice, G. Luo for
   genotyping, M. Davis for advice on staining and G. Martins for
   performing immunohistochemistry. This work was supported by National
   Science Foundation CAREER Award 0954243, the Multiscale Systems Research
   Center and the Defense Advanced Research Projects Agency contract
   N66001-10-C-2008 to J. M. C., and the Division of Intramural Clinical
   and Basic Research of the National Institute on Alcohol Abuse and
   Alcoholism, Marie Curie International Reintegration Grant 239527 and
   European Research Council STG 243393 to R.M.C.
NR 30
TC 112
Z9 113
U1 4
U2 38
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD MAR 15
PY 2012
VL 483
IS 7389
BP 331
EP 335
DI 10.1038/nature10845
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 908HP
UT WOS:000301481800049
PM 22388818
ER

PT J
AU Kopald, BE
   Mirra, KM
   Egan, MF
   Weinberger, DR
   Goldberg, TE
AF Kopald, Brandon E.
   Mirra, Kathryn M.
   Egan, Michael F.
   Weinberger, Daniel R.
   Goldberg, Terry E.
TI Magnitude of Impact of Executive Functioning and IQ on Episodic Memory
   in Schizophrenia
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Episodic memory; executive functioning; intelligence; memory; prefrontal
   cortex; schizophrenia
ID 1ST-EPISODE PSYCHOSIS; HEALTHY CONTROLS; DEFICITS; RECOGNITION;
   METAANALYSIS; IMPAIRMENT; ACTIVATION; SIBLINGS
AB Background: Research has implicated IQ and executive function (EF) as contributors to episodic memory impairments in schizophrenia. However, it has been difficult to quantitatively apportion the respective contributions of these factors. We conducted a series of analyses to objectively parse the associated variance and to determine to what extent episodic memory impairment in schizophrenia is independent of IQ and EF.
   Methods: Participants included 323 schizophrenia patients and 327 healthy controls from the National Insitute of Mental Health Sibling Study. Neurocognitive tests assessing IQ, EF, and episodic memory were administered. We examined group differences while controlling for IQ or EF in analyses of covariance, we used linear regression to quantify the amount of variance not explained by IQ or EF, and we matched control and patient subgroups on IQ or EF to determine if memory measures remained different.
   Results: Analyses of covariance revealed significant group differences between schizophrenia individuals and healthy control subjects across multiple episodic memory measures after controlling for IQ or EF. Furthermore, regressions with IQ and/or EF factors entered left more than 50% of variance in memory unaccounted. Follow-up true score variance analyses indicated that the majority of this variance was directly related to memory function. Matched subgroups also yielded subgroup differences on all memory measures.
   Conclusions: Findings across the multiple statistical strategies suggested that the mechanisms underlying the memory impairment in schizophrenia are fully attributable neither to IQ nor EF. Rather, they most likely reflect compromises in episodic memory processing itself and, by inference, the medial temporal system.
C1 [Kopald, Brandon E.; Mirra, Kathryn M.; Goldberg, Terry E.] Hofstra N Shore Long Isl Jewish Sch Med, Feinstein Inst Med Res Psychiat Res, Manhasset, NY 11030 USA.
   [Egan, Michael F.; Weinberger, Daniel R.] NIMH, Genes Cognit & Psychosis Program, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Goldberg, TE (reprint author), Hofstra N Shore Long Isl Jewish Sch Med, Feinstein Inst Med Res Psychiat Res, 350 Community Dr, Manhasset, NY 11030 USA.
EM tgoldber@nshs.edu
FU National Institutes of Health [P50 MH080173, HHSN-271-2009-00019C]
FX This work was supported in part by National Institutes of Health Grants
   P50 MH080173 and HHSN-271-2009-00019C (BK, KM, TG). Dr. Goldberg has
   served as a consultant for Merck and GlaxoSmithKline and receives
   royalties for use of a cognitive test. Dr. Egan worked on this study
   while employed by the federal government; he is now an employee of
   Merck. Dr. Weinberger worked on this study while employed by the federal
   government. Drs. Kopald and Mirra report no biomedical financial
   interests or potential conflicts of interest.
NR 27
TC 12
Z9 12
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAR 15
PY 2012
VL 71
IS 6
BP 545
EP 551
DI 10.1016/j.biopsych.2011.11.021
PG 7
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 899BX
UT WOS:000300789100015
PM 22265665
ER

PT J
AU Anticevic, A
   Van Snellenberg, JX
   Barch, DM
AF Anticevic, Alan
   Van Snellenberg, Jared X.
   Barch, Deanna M.
TI Neurobiology of Emotional Dysfunction in Schizophrenia: New Directions
   Revealed Through Meta-Analyses
SO BIOLOGICAL PSYCHIATRY
LA English
DT Letter
ID FACIAL EXPRESSION; EXPERIENCE
C1 [Anticevic, Alan] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA.
   [Anticevic, Alan] NIAAA, Ctr Translat Neurosci Alcoholism, New Haven, CT USA.
   [Anticevic, Alan] Connecticut Mental Hlth Ctr, Abraham Ribicoff Res Facil, New Haven, CT 06519 USA.
   [Van Snellenberg, Jared X.] New York State Psychiat Inst & Hosp, Div Cognit Neurosci, New York, NY 10032 USA.
   [Van Snellenberg, Jared X.] Columbia Univ, Dept Psychol, New York, NY 10027 USA.
   [Barch, Deanna M.] Washington Univ St Louis, Dept Psychol, St Louis, MO USA.
   [Barch, Deanna M.] Washington Univ St Louis, Dept Psychiat, St Louis, MO USA.
   [Barch, Deanna M.] Washington Univ St Louis, Dept Radiol, St Louis, MO USA.
RP Anticevic, A (reprint author), Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA.
EM alan.anticevic@yale.edu
RI Anticevic, Alan/E-7868-2010; Van Snellenberg, Jared/F-7889-2013; Barch,
   Deanna/G-8638-2013
OI Van Snellenberg, Jared/0000-0003-2442-2008; 
NR 17
TC 4
Z9 4
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAR 15
PY 2012
VL 71
IS 6
BP E23
EP E24
DI 10.1016/j.biopsych.2011.10.039
PG 2
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 899BX
UT WOS:000300789100005
PM 22206874
ER

PT J
AU Swales, KE
   Moore, R
   Truss, NJ
   Tucker, A
   Warner, TD
   Negishi, M
   Bishop-Bailey, D
AF Swales, Karen E.
   Moore, Rick
   Truss, Nicola J.
   Tucker, Arthur
   Warner, Timothy D.
   Negishi, Masahiko
   Bishop-Bailey, David
TI Pregnane X receptor regulates drug metabolism and transport in the
   vasculature and protects from oxidative stress
SO CARDIOVASCULAR RESEARCH
LA English
DT Article
DE Pregnane X receptor; Nuclear receptors; Vascular endothelium; Vascular
   smooth muscle cells; Cytochrome P450
ID BLOOD-BRAIN-BARRIER; ENDOTHELIAL-CELL LINE; SMOOTH-MUSCLE-CELLS;
   P-GLYCOPROTEIN; UP-REGULATION; CYTOCHROME-P450 ENZYMES; HYPERPOLARIZING
   FACTOR; PLATELET-AGGREGATION; REDUCTASE INHIBITORS; NUCLEAR RECEPTORS
AB Circulating endogenous, dietary, and foreign chemicals can contribute to vascular dysfunction. The mechanism by which the vasculature protects itself from these chemicals is unknown. This study investigates whether the pregnane X receptor (PXR), the major transcriptional regulator of hepatic drug metabolism and transport that responds to such xenobiotics, mediates vascular protection by co-ordinating a defence gene programme in the vasculature.
   PXR was detected in primary human and rat aortic endothelial and smooth muscle cells (SMC) and blood vessels including the human and rat aorta. Metabolic PXR target genes cytochrome P450 3A, 2B, 2C, and glutathione S-transferase mRNA and activity were induced by PXR ligands in rodent and human vascular cells and absent in the aortas from PXR-null mice stimulated in vivo or in rat aortic SMC expressing dominant-negative PXR. Activation of aortic PXR by classical agonists had several protective effects: increased xenobiotic metabolism demonstrated by bioactivation of the pro-drug clopidogrel, which reduced adenosine diphosphate-induced platelet aggregation; increased expression of multidrug resistance protein 1, mediating chemical efflux from the vasculature; and protection from reactive oxygen species-mediated cell death.
   PXR co-ordinately up-regulates drug metabolism, transport, and antioxidant genes to protect the vasculature from endogenous and exogenous insults, thus representing a novel gatekeeper for vascular defence.
C1 [Swales, Karen E.] Univ Surrey, Fac Hlth & Med Sci, Guildford GU2 7XH, Surrey, England.
   [Moore, Rick; Negishi, Masahiko] NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA.
   [Truss, Nicola J.; Tucker, Arthur; Warner, Timothy D.; Bishop-Bailey, David] Barts & London Queen Marys Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England.
RP Swales, KE (reprint author), Univ Surrey, Fac Hlth & Med Sci, Guildford GU2 7XH, Surrey, England.
EM k.swales@surrey.ac.uk
RI Warner, Timothy/A-1980-2009
OI Warner, Timothy/0000-0003-3988-4408
FU Barts and the London Charitable Trust [427/438]; Wellcome Trust
   [074361/Z/04/Z]; European Community [LSHM-CT-2004-0050333]; British
   Heart Foundation [BS/02/002]; National Institutes of Health; National
   Institute of Environmental Health Sciences
FX This work was supported by a Barts and the London Charitable Trust,
   research and advisory board non-clinical research fellowship (427/438)
   to K. E. S.; the Wellcome Trust (074361/Z/04/Z) to D.B.-B.; European
   Community FP6 funding (LSHM-CT-2004-0050333) to T. D. W.; the British
   Heart Foundation (BS/02/002) to D.B.-B.; and the Intramural Research
   Program of the National Institutes of Health and National Institute of
   Environmental Health Sciences to M.N.
NR 49
TC 18
Z9 18
U1 2
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0008-6363
J9 CARDIOVASC RES
JI Cardiovasc. Res.
PD MAR 15
PY 2012
VL 93
IS 4
BP 674
EP 681
DI 10.1093/cvr/cvr330
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 901TA
UT WOS:000300988500018
PM 22166712
ER

PT J
AU Chattopadhyay, M
   Kodela, R
   Nath, N
   Dastagirzada, YM
   Velazquez-Martinez, CA
   Boring, D
   Kashfi, K
AF Chattopadhyay, Mitali
   Kodela, Ravinder
   Nath, Niharika
   Dastagirzada, Yosef M.
   Velazquez-Martinez, Carlos A.
   Boring, Daniel
   Kashfi, Khosrow
TI Hydrogen sulfide-releasing NSAIDs inhibit the growth of human cancer
   cells: A general property and evidence of a tissue type-independent
   effect
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE Hydrogen sulfide; NSAIDs; Cancer prevention; COX-independent
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; OXIDE-DONATING ASPIRIN;
   NITRIC-OXIDE; COLON-CANCER; GASTROINTESTINAL-TRACT; POSITIONAL
   ISOMERISM; IN-VITRO; APOPTOSIS; PROLIFERATION; PHOSPHORYLATION
AB Hydrogen sulfide-releasing non-steroidal anti-inflammatory drugs (HS-NSAIDs) are an emerging novel class of compounds with significant anti-inflammatory properties. They consist of a traditional NSAID to which an H2S-releasing moiety is covalently attached. We examined the effects of four different HS-NSAIDs on the growth properties of eleven different human cancer cell lines of six different tissue origins. Human colon, breast, pancreatic, prostate, lung, and leukemia cancer cell lines were treated with HS-aspirin, -sulindac, -iburofen, -naproxen, and their traditional counterparts. HS-NSAIDs inhibited the growth of all cancer cell lines studied, with potencies of 28- to >3000-fold greater than that of their traditional counterparts. HS-aspirin (HS-ASA) was consistently the most potent. HS-NSAIDs inhibited cell proliferation, induced apoptosis, and caused G(0)/G(1) cell cycle block. Metabolism of HS-ASA by colon cells showed that the acetyl group of ASA was hydrolyzed rapidly, followed by hydrolysis of the ester bond linking the salicylate anion to the H2S releasing moiety, producing salicylic acid and ADT-OH from which H2S is released. In reconstitution studies, ASA and ADT-OH were individually less active than the intact HS-ASA towards cell growth inhibition. Additionally, the combination of these two components representing a fairly close approximation to the intact HS-ASA, was 95-fold less active than the intact HS-ASA for growth inhibition. Taken together, these results demonstrate that HS-NSAIDs have potential anti-growth activity against a wide variety of human cancer cells. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Chattopadhyay, Mitali; Kodela, Ravinder; Dastagirzada, Yosef M.; Kashfi, Khosrow] CUNY, Sch Med, Dept Physiol & Pharmacol, Sophie Davis Sch Biomed Educ, New York, NY 10031 USA.
   [Nath, Niharika] New York Inst Technol, Dept Life Sci, New York, NY 10023 USA.
   [Velazquez-Martinez, Carlos A.] Univ Alberta, Fac Pharm & Pharmaceut Sci, Edmonton, AB T6G 2N8, Canada.
   [Boring, Daniel] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Kashfi, K (reprint author), CUNY, Sch Med, Dept Physiol & Pharmacol, Sophie Davis Sch Biomed Educ, 138th St & Convent Ave, New York, NY 10031 USA.
EM kashfi@med.cuny.edu
FU National Cancer Institute through ThermoFisher [FBS-43312-26]
FX Supported in part by the National Cancer Institute through a subcontract
   from ThermoFisher, contract # FBS-43312-26.
NR 33
TC 45
Z9 47
U1 4
U2 36
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 MAR 15
PY 2012
VL 83
IS 6
BP 715
EP 722
DI 10.1016/j.bcp.2011.12.018
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 898QP
UT WOS:000300757200003
PM 22222427
ER

PT J
AU Chattopadhyay, M
   Kodela, R
   Nath, N
   Barsegian, A
   Boring, D
   Kashfi, K
AF Chattopadhyay, Mitali
   Kodela, Ravinder
   Nath, Niharika
   Barsegian, Arpine
   Boring, Daniel
   Kashfi, Khosrow
TI Hydrogen sulfide-releasing aspirin suppresses NF-kappa B signaling in
   estrogen receptor negative breast cancer cells in vitro and in vivo
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE Hydrogen sulfide; Estrogen receptor negative breast cancer; NF-kappa B;
   Thioredoxin reductase; Chemoprevention
ID DNA-BINDING ACTIVITY; THIOREDOXIN REDUCTASE; MYOCARDIAL-ISCHEMIA;
   GROWTH-INHIBITION; OXIDATIVE STRESS; ACTIVATION; EXPRESSION; APOPTOSIS;
   THERAPY; ACID
AB Hormone-dependent estrogen receptor positive (ER+) breast cancers generally respond well to antiestrogen therapy. Unfortunately, hormone-independent estrogen receptor negative (ER) breast cancers are aggressive, respond poorly to current treatments and have a poor prognosis. New approaches and targets are needed for the prevention and treatment of ER breast cancer. The NF-kappa B signaling pathway is strongly implicated in ER tumor genesis, constituting a possible target for treatment. Hydrogen sulfide-releasing aspirin (HS-ASA), a novel and safer derivative of aspirin, has shown promise as an anti-cancer agent. We examined the growth inhibitory effect of HS-ASA via alterations in cell proliferation, cell cycle phase transitions, and apoptosis, using MDA-MB-231 cells as a model of triple negative breast cancer. Tumor xenografts in mice, representing human ER breast cancer, were evaluated for reduction in tumor size, followed by immunohistochemical analysis for proliferation, apoptosis and expression of NF-kappa B. HS-ASA suppressed the growth of MDA-MB-231 cells by induction of G(0)/G(1) arrest and apoptosis, down-regulation of NF-kappa B, reduction of thioredoxin reductase activity, and increased levels reactive oxygen species. Tumor xenografts in mice, were significantly reduced in volume and mass by HS-ASA treatment. The decrease in tumor mass was associated with inhibition of cell proliferation, induction of apoptosis and decrease in NF-kappa B levels in vivo. HS-ASA has anti-cancer potential against ER- breast cancer and merits further study. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Chattopadhyay, Mitali; Kodela, Ravinder; Barsegian, Arpine; Kashfi, Khosrow] CUNY, Sch Med, Dept Physiol & Pharmacol, Sophie Davis Sch Biomed Educ, New York, NY 10031 USA.
   [Nath, Niharika] New York Inst Technol, Dept Life Sci, New York, NY 10023 USA.
   [Boring, Daniel] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Kashfi, K (reprint author), CUNY, Sch Med, Dept Physiol & Pharmacol, Sophie Davis Sch Biomed Educ, 138th St & Convent Ave, New York, NY 10031 USA.
EM kashfi@med.cuny.edu
RI perumal, murugiah/D-1565-2012
FU National Cancer Institute through ThermoFisher [FBS-43312-26]
FX Supported in part by the National Cancer Institute through a subcontract
   from ThermoFisher, contract # FBS-43312-26.
NR 78
TC 32
Z9 33
U1 1
U2 9
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0006-2952
EI 1873-2968
J9 BIOCHEM PHARMACOL
JI Biochem. Pharmacol.
PD MAR 15
PY 2012
VL 83
IS 6
BP 723
EP 732
DI 10.1016/j.bcp.2011.12.019
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 898QP
UT WOS:000300757200004
PM 22209867
ER

PT J
AU Chattopadhyay, M
   Kodela, R
   Nath, N
   Street, CR
   Velazquez-Martinez, CA
   Boring, D
   Kashfi, K
AF Chattopadhyay, Mitali
   Kodela, Ravinder
   Nath, Niharika
   Street, Cherease R.
   Velazquez-Martinez, Carlos A.
   Boring, Daniel
   Kashfi, Khosrow
TI Hydrogen sulfide-releasing aspirin modulates xenobiotic metabolizing
   enzymes in vitro and in vivo
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE Xenobiotic metabolizing enzymes; GST; NOQ1; UGT; CYP 1A1; Hydrogen
   sulfide; NSAIDs
ID GLUTATHIONE S-TRANSFERASES; ISCHEMIA-REPERFUSION INJURY; NONSTEROIDAL
   ANTIINFLAMMATORY DRUGS; SMOOTH-MUSCLE-CELLS; MYOCARDIAL-ISCHEMIA;
   CARNITINE PALMITOYLTRANSFERASE; UDP-GLUCURONOSYLTRANSFERASES; CANCER
   CHEMOPREVENTION; CHEMICAL CARCINOGENS; OXIDATIVE STRESS
AB The balance between phase-I carcinogen-activating and phase-II detoxifying xenobiotic metabolizing enzymes is critical to determining an individual's risk for cancer. We evaluated the effect of Hydrogen sulfide-releasing aspirin (HS-ASA) on xenobiotic metabolizing enzymes in HT-29 human colon and Hepa 1c1c7 mouse liver adenocarcinoma cells and in Wistar rats. HS-ASA inhibited the growth of HT-29 and Hepa 1c1c7 cells, with an IC50 of 3.2 +/- 0.3 mu M and 4.2 +/- 0.4 mu M, respectively. The IC50 for ASA in both cell lines was greater than 5000 mu M at 24 h. In these cell lines, HS-ASA caused a dose-dependent increase in activity and expression of the phase-II enzymes glutathione S-transferase (GST) and NAD(P)H:quinoneoxireductase (NQO1). It also caused an increase in UDP-glucuronosyltransferase (UGT) expression. The levels of CYP 1A1 a phase-I enzyme was increased by HS-ASA in both cell lines. Pretreatment of cells with NaF, an esterase inhibitor, abrogated the HS-ASA-mediated increases in NQO1 enzyme activity. HS-ASA increased the protein levels of the transcription factor Nrf2, which is a regulator of the phase-II enzymes. In vivo, HS-ASA at 100 mg/kg/day had no effect on rat's weights; it induced a 3.4-fold and 1.4-fold increase in hepatic GST and NQ01 enzyme activities, respectively. GST and NQO1 protein levels were also increased. In contrast to that in cultured cells, CYP 1A1 protein levels were not altered in vivo. Therefore, HS-ASA induces phase-II enzymes, at least in part, through the action of H2S and by modulating Nrf2; these effects may be part of its mechanism of action against carcinogenesis. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Chattopadhyay, Mitali; Kodela, Ravinder; Street, Cherease R.; Kashfi, Khosrow] CUNY, Sch Med, Dept Physiol & Pharmacol, Sophie Davis Sch Biomed Educ, New York, NY 10031 USA.
   [Nath, Niharika] New York Inst Technol, Dept Life Sci, New York, NY 10023 USA.
   [Velazquez-Martinez, Carlos A.] Univ Alberta, Fac Pharm & Pharmaceut Sci, Edmonton, AB T6G 2N8, Canada.
   [Boring, Daniel] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Kashfi, K (reprint author), CUNY, Sch Med, Dept Physiol & Pharmacol, Sophie Davis Sch Biomed Educ, 138th St & Convent Ave, New York, NY 10031 USA.
EM kashfi@med.cuny.edu
RI Ji, Haofeng/G-6206-2012
FU National Cancer Institute through ThermoFisher [FBS-43312-26]
FX Supported in part by the National Cancer Institute through a subcontract
   from ThermoFisher, contract #FBS-43312-26.
NR 61
TC 16
Z9 16
U1 3
U2 13
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 MAR 15
PY 2012
VL 83
IS 6
BP 733
EP 740
DI 10.1016/j.bcp.2011.12.020
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 898QP
UT WOS:000300757200005
PM 22209714
ER

PT J
AU Prendergast, A
   Linbo, TH
   Swarts, T
   Ungos, JM
   McGraw, HF
   Krispin, S
   Weinstein, BM
   Raible, DW
AF Prendergast, Andrew
   Linbo, Tor H.
   Swarts, Tanya
   Ungos, Josette M.
   McGraw, Hillary F.
   Krispin, Shlomo
   Weinstein, Brant M.
   Raible, David W.
TI The metalloproteinase inhibitor Reck is essential for zebrafish DRG
   development
SO DEVELOPMENT
LA English
DT Article
DE reck; Neural crest; Neurogenesis; Zebrafish
ID CYSTEINE-RICH PROTEIN; KAZAL MOTIFS RECK; METASTASIS SUPPRESSOR RECK;
   DORSAL-ROOT GANGLIA; CELL LUNG-CANCER; IN-SITU HYBRIDIZATION;
   NEURAL-CREST; DOWN-REGULATION; PROGNOSTIC-SIGNIFICANCE;
   CLINICAL-SIGNIFICANCE
AB The neural crest is a migratory, multipotent cell lineage that contributes to myriad tissues, including sensory neurons and glia of the dorsal root ganglia (DRG). To identify genes affecting cell fate specification in neural crest, we performed a forward genetic screen for mutations causing DRG deficiencies in zebrafish. This screen yielded a mutant lacking all DRG, which we named sensory deprived (sdp). We identified a total of four alleles of sdp, all of which possess lesions in the gene coding for reversion-inducing cysteine-rich protein containing Kazal motifs (Reck). Reck is an inhibitor of metalloproteinases previously shown to regulate cell motility. We found reck function to be both necessary for DRG formation and sufficient to rescue the sdp phenotype. reck is expressed in neural crest cells and is required in a cell-autonomous fashion for appropriate sensory neuron formation. In the absence of reck function, sensory neuron precursors fail to migrate to the position of the DRG, suggesting that this molecule is crucial for proper migration and differentiation.
C1 [Prendergast, Andrew; Raible, David W.] Univ Washington, Grad Program Neurobiol & Behav, Seattle, WA 98195 USA.
   [Ungos, Josette M.; McGraw, Hillary F.; Raible, David W.] Univ Washington, Mol & Cellular Biol Grad Program, Seattle, WA 98195 USA.
   [Prendergast, Andrew; Linbo, Tor H.; Swarts, Tanya; Ungos, Josette M.; McGraw, Hillary F.; Raible, David W.] Univ Washington, Dept Biol Struct, Seattle, WA 98195 USA.
   [Krispin, Shlomo; Weinstein, Brant M.] NICHHD, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
RP Raible, DW (reprint author), Univ Washington, Grad Program Neurobiol & Behav, Seattle, WA 98195 USA.
EM draible@u.washington.edu
FU National Institute of General Medical Sciences [NRSA 2T32 GM007270];
   National Institute of Neurological Disorders and Stroke [NS057220];
   Eunice Kennedy Shriver National Institute of Child Health and Human
   Development [HD001011]
FX This investigation was supported in part by the National Institute of
   General Medical Sciences [NRSA 2T32 GM007270]; the National Institute of
   Neurological Disorders and Stroke [NS057220]; and the intramural program
   of the Eunice Kennedy Shriver National Institute of Child Health and
   Human Development [HD001011 to B. W.]. Deposited in PMC for release
   after 12 months.
NR 69
TC 19
Z9 19
U1 0
U2 1
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
   CAMBS, ENGLAND
SN 0950-1991
J9 DEVELOPMENT
JI Development
PD MAR 15
PY 2012
VL 139
IS 6
BP 1141
EP 1152
DI 10.1242/dev.072439
PG 12
WC Developmental Biology
SC Developmental Biology
GA 897HY
UT WOS:000300640700011
PM 22296847
ER

PT J
AU Busser, BW
   Shokri, L
   Jaeger, SA
   Gisselbrecht, SS
   Singhania, A
   Berger, MF
   Zhou, B
   Bulyk, ML
   Michelson, AM
AF Busser, Brian W.
   Shokri, Leila
   Jaeger, Savina A.
   Gisselbrecht, Stephen S.
   Singhania, Aditi
   Berger, Michael F.
   Zhou, Bo
   Bulyk, Martha L.
   Michelson, Alan M.
TI Molecular mechanism underlying the regulatory specificity of a
   Drosophila homeodomain protein that specifies myoblast identity
SO DEVELOPMENT
LA English
DT Article
DE Homeodomain; Myoblast; Gene regulation
ID TRANSCRIPTION FACTORS; SEQUENCE LOGOS; HOMEOBOX GENE; HOX PROTEINS;
   MUSCLE; DNA; MESODERM; DIVERSIFICATION; EXPRESSION; DIFFERENTIATION
AB A subfamily of Drosophila homeodomain (HD) transcription factors (TFs) controls the identities of individual muscle founder cells (FCs). However, the molecular mechanisms by which these TFs generate unique FC genetic programs remain unknown. To investigate this problem, we first applied genome-wide mRNA expression profiling to identify genes that are activated or repressed by the muscle HD TFs Slouch (Slou) and Muscle segment homeobox (Msh). Next, we used protein-binding microarrays to define the sequences that are bound by Slou, Msh and other HD TFs that have mesodermal expression. These studies revealed that a large class of HDs, including Slou and Msh, predominantly recognize TAAT core sequences but that each HD also binds to unique sites that deviate from this canonical motif. To understand better the regulatory specificity of an individual FC identity HD, we evaluated the functions of atypical binding sites that are preferentially bound by Slou relative to other HDs within muscle enhancers that are either activated or repressed by this TF. These studies showed that Slou regulates the activities of particular myoblast enhancers through Slou-preferred sequences, whereas swapping these sequences for sites that are capable of binding to multiple HD family members does not support the normal regulatory functions of Slou. Moreover, atypical Slou-binding sites are overrepresented in putative enhancers associated with additional Slou-responsive FC genes. Collectively, these studies provide new insights into the roles of individual HD TFs in determining cellular identity, and suggest that the diversity of HD binding preferences can confer regulatory specificity.
C1 [Shokri, Leila; Gisselbrecht, Stephen S.; Berger, Michael F.; Zhou, Bo; Bulyk, Martha L.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA.
   [Bulyk, Martha L.] Harvard Univ, Sch Med, Harvard MIT Div Hlth Sci & Technol HST, Boston, MA 02115 USA.
   [Busser, Brian W.; Singhania, Aditi; Michelson, Alan M.] NHLBI, Lab Dev Syst Biol, Genet & Dev Biol Ctr, Div Intramural Res,NIH, Bethesda, MD 20892 USA.
   [Jaeger, Savina A.] Novartis Inst Biomed Res, Cambridge, MA 02139 USA.
   [Bulyk, Martha L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Bulyk, Martha L.] Harvard Univ, Comm Higher Degrees Biophys, Cambridge, MA 02138 USA.
   [Bulyk, Martha L.] Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA.
RP Bulyk, ML (reprint author), Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA.
EM mlbulyk@receptor.med.harvard.edu; michelsonam@nhlbi.nih.gov
OI Gisselbrecht, Stephen/0000-0001-8723-902X
FU National Institutes of Health/National Institutes of General Medical
   Sciences (NIH/NIGMS) [U01 GM076603]; NIH/National Human Genome Research
   Institute (NHGRI) [R01 HG005287]; National Heart, Blood and Lung
   Institute (NHLBI) Division of Intramural Research; NIH [5 T32
   GM007748-31]; NIH NRSA [1 F32 GM090645-01A1]
FX This work was funded by National Institutes of Health/National
   Institutes of General Medical Sciences (NIH/NIGMS) [U01 GM076603 to M.
   L. B.], by NIH/National Human Genome Research Institute (NHGRI) [R01
   HG005287 to M. L. B.], by the National Heart, Blood and Lung Institute
   (NHLBI) Division of Intramural Research (A. M. M.), by a NIH Training
   Grant [5 T32 GM007748-31 to L. S.], and by a NIH NRSA [1 F32
   GM090645-01A1 to L. S.]. Deposited in PMC for immediate release.
NR 64
TC 20
Z9 20
U1 0
U2 1
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
   CAMBS, ENGLAND
SN 0950-1991
J9 DEVELOPMENT
JI Development
PD MAR 15
PY 2012
VL 139
IS 6
BP 1164
EP 1174
DI 10.1242/dev.077362
PG 11
WC Developmental Biology
SC Developmental Biology
GA 897HY
UT WOS:000300640700013
PM 22296846
ER

PT J
AU Bagni, R
   Whitby, D
AF Bagni, Rachel
   Whitby, Denise
TI Age of Infection and Risk of Virally Associated Cancers: New Clues to an
   Old Puzzle
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Editorial Material
ID EPSTEIN-BARR-VIRUS; BURKITTS-LYMPHOMA; MALARIA; ANTIBODIES
C1 [Whitby, Denise] NCI, Viral Oncol Sect, AIDS Vaccine Program, SAIC Frederick, Ft Detrick, MD 21702 USA.
   [Bagni, Rachel] NCI, Adv Technol Program, Ft Detrick, MD 21702 USA.
RP Whitby, D (reprint author), NCI, Viral Oncol Sect, AIDS Vaccine Program, SAIC Frederick, 1050 Boyles St,Bldg 535,Rm 409,POB B, Ft Detrick, MD 21702 USA.
EM whitbyd@mail.nih.gov
FU NCI NIH HHS [N01CO12400]
NR 10
TC 3
Z9 3
U1 0
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 MAR 15
PY 2012
VL 205
IS 6
BP 873
EP 874
DI 10.1093/infdis/jir871
PG 2
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 898FU
UT WOS:000300724100003
PM 22301634
ER

PT J
AU Heegaard, NHH
   Schetter, AJ
   Welsh, JA
   Yoneda, M
   Bowman, ED
   Harris, CC
AF Heegaard, Niels H. H.
   Schetter, Aaron J.
   Welsh, Judith A.
   Yoneda, Mitsuhiro
   Bowman, Elise D.
   Harris, Curtis C.
TI Circulating micro-RNA expression profiles in early stage nonsmall cell
   lung cancer
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE micro-RNA; lung cancer; early detection
ID PREDICTS SURVIVAL; TRAIL RESISTANCE; BIOMARKERS; SERUM; PROGNOSIS;
   DIAGNOSIS; PCR; MICRORNA-223; SIGNATURE; PLATELETS
AB Circulating micro-RNA (miR) profiles have been proposed as promising diagnostic and prognostic biomarkers for cancer, including lung cancer. We have developed methods to accurately and reproducibly measure micro-RNA levels in serum and plasma. Here, we study paired serum and plasma samples from 220 patients with early stage nonsmall cell lung cancer (NSCLC) and 220 matched controls. We use qRT-PCR to measure the circulating levels of 30 different miRs that have previously been reported to be differently expressed in lung cancer tissue. Duplicate RNA extractions were performed for 10% of all samples, and micro-RNA measurements were highly correlated among those duplicates. This demonstrates high reproducibility of our assay. The expressions of miR-146b, miR-221, let-7a, miR-155, miR-17-5p, miR-27a and miR-106a were significantly reduced in the serum of NSCLC cases, while miR-29c was significantly increased. No significant differences were observed in plasma of patients compared with controls. Overall, expression levels in serum did not correlate well with levels in plasma. In secondary analyses, reduced plasma expression of let-7b was modestly associated with worse cancer-specific mortality in all patients, and reduced serum expression of miR-223 was modestly associated with cancer-specific mortality in stage IA/B patients. MiR profiles also showed considerable differences comparing African American and European Americans. In summary, we found significant differences in miR expression when comparing cases and controls and find evidence that expression of let-7b is associated with prognosis in NSCLC.
C1 [Heegaard, Niels H. H.; Schetter, Aaron J.; Welsh, Judith A.; Yoneda, Mitsuhiro; Bowman, Elise D.; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Heegaard, Niels H. H.] Statens Serum Inst, Dept Clin Biochem & Immunol, DK-2300 Copenhagen, Denmark.
RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Room 3068,Bldg 37,37 Convent Dr, Bethesda, MD 20892 USA.
EM Curtis_Harris@nih.gov
FU NIH; Statens Serum Institut
FX Grant sponsors: NIH Intramural Program, Statens Serum Institut
NR 38
TC 131
Z9 146
U1 5
U2 36
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 MAR 15
PY 2012
VL 130
IS 6
BP 1378
EP 1386
DI 10.1002/ijc.26153
PG 9
WC Oncology
SC Oncology
GA 878IV
UT WOS:000299250700015
PM 21544802
ER

PT J
AU Kitahara, CM
   Platz, EA
   Park, Y
   Hollenbeck, AR
   Schatzkin, A
   de Gonzalez, AB
AF Kitahara, Cari M.
   Platz, Elizabeth A.
   Park, Yikyung
   Hollenbeck, Albert R.
   Schatzkin, Arthur
   de Gonzalez, Amy Berrington
TI Body fat distribution, weight change during adulthood, and thyroid
   cancer risk in the NIH-AARP Diet and Health Study
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE thyroid cancer; anthropometry; obesity; prospective study
ID MASS INDEX; POOLED ANALYSIS; LARGE COHORT; ANTHROPOMETRIC FACTORS; WAIST
   CIRCUMFERENCE; NATIONAL-INSTITUTES; PHYSICAL-ACTIVITY; NEW-CALEDONIA;
   WOMEN; MEN
AB Body mass index (BMI) has been positively associated with thyroid cancer risk in several studies, but the underlying mechanisms remain unclear. We examined the associations for waist and hip circumference and weight change during adulthood with thyroid cancer risk among 125,347 men and 72,363 women in the NIH-AARP Diet and Health Study who completed a second mailed questionnaire in 19961997. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated separately by sex and adjusted for race/ethnicity, education and smoking status. During follow-up (median = 10.1 years), 106 men and 105 women were diagnosed with a first primary thyroid cancer, as identified through linkage to state cancer registries. Having a large waist circumference (above the clinical cutpoint for normal: >102 cm in men and >88 cm in women) was associated with increased risk in both men (HR = 1.79, 95% CI: 1.212.63) and women (HR = 1.54, 95% CI: 1.052.26). Having both a large waist and BMI in the obese range (=30 kg/m2) approximately doubled the risk of thyroid cancer (HR in men = 2.13, 95% CI: 1.183.85; HR in women = 1.91, 95% CI: 1.313.25) compared to having a normal waist circumference/normal BMI (18.524.9 kg/m2). We also observed positive association for weight gain between ages 1835 in men (gained =10.0 kg vs. lost/gained <5 kg, HR = 1.49, 95% CI: 0.932.39, p-trend = 0.03), but the association was less pronounced in women. No clear association for weight gain in later life was observed. These results support a potential role for hormonal and metabolic parameters common to central adiposity in thyroid carcinogenesis.
C1 [Kitahara, Cari M.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
   [Kitahara, Cari M.; Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
   [Hollenbeck, Albert R.] AARP, Washington, DC USA.
RP Kitahara, CM (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
EM kitaharac@mail.nih.gov
RI Kitahara, Cari/R-8267-2016; 
OI Park, Yikyung/0000-0002-6281-489X
FU National Institutes of Health; National Cancer Institute
FX Grant sponsors: Intramural Research Program of the National Institutes
   of Health and the National Cancer Institute
NR 46
TC 19
Z9 20
U1 0
U2 2
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 MAR 15
PY 2012
VL 130
IS 6
BP 1411
EP 1419
DI 10.1002/ijc.26161
PG 9
WC Oncology
SC Oncology
GA 878IV
UT WOS:000299250700019
PM 21544808
ER

PT J
AU de Filippis, I
   de Lemos, APS
   Hostetler, JB
   Wollenberg, K
   Sacchi, CT
   Harrison, LH
   Bash, MC
   Prevots, DR
AF de Filippis, Ivano
   de Lemos, Ana Paula S.
   Hostetler, Jessica B.
   Wollenberg, Kurt
   Sacchi, Claudio T.
   Harrison, Lee H.
   Bash, Margaret C.
   Prevots, D. Rebecca
TI Molecular Epidemiology of Neisseria meningitidis Serogroup B in Brazil
SO PLOS ONE
LA English
DT Article
ID MENINGOCOCCAL DISEASE; FACTOR-H; VACCINE CANDIDATE; SAO-PAULO; PROTEIN;
   DIVERSITY; STRAINS; NADA; PORA; IDENTIFICATION
AB Background: Neisseria meningitidis serogroup B has been predominant in Brazil, but no broadly effective vaccine is available to prevent endemic meningococcal disease. To understand genetic diversity among serogroup B strains in Brazil, we selected a nationally representative sample of clinical disease isolates from 2004, and a temporally representative sample for the state of Sao Paulo (1988-2006) for study (n = 372).
   Methods: We performed multi-locus sequence typing (MLST) and sequence analysis of five outer membrane protein (OMP) genes, including novel vaccine targets fHbp and nadA.
   Results: In 2004, strain B:4:P1.15,19 clonal complex ST-32/ET-5 (cc32) predominated throughout Brazil; regional variation in MLST sequence type (ST), fetA, and porB was significant but diversity was limited for nadA and fHbp. Between 1988 and 1996, the Sao Paulo isolates shifted from clonal complex ST-41/44/Lineage 3 (cc41/44) to cc32. OMP variation was associated with but not predicted by cc or ST. Overall, fHbp variant 1/subfamily B was present in 80% of isolates and showed little diversity. The majority of nadA were similar to reference allele 1.
   Conclusions: A predominant serogroup B lineage has circulated in Brazil for over a decade with significant regional and temporal diversity in ST, fetA, and porB, but not in nadA and fHbp.
C1 [de Filippis, Ivano] Oswaldo Cruz Fdn FIOCRUZ, Natl Qual Control Inst INCQS, Rio De Janeiro, Brazil.
   [de Filippis, Ivano; Bash, Margaret C.] US FDA, Lab Bacterial Polysaccharides, CBER, Bethesda, MD 20014 USA.
   [de Filippis, Ivano; Prevots, D. Rebecca] NIAID, Epidemiol Unit, Lab Clin Infect Dis, Div Intramural Res,NIH, Bethesda, MD 20892 USA.
   [de Lemos, Ana Paula S.] IAL, Dept Bacteriol, Sao Paulo, Brazil.
   [Hostetler, Jessica B.] JCVI, Rockville, MD USA.
   [Wollenberg, Kurt] NIAID, Off Cyberinfrastruct & Computat Biol OCICB, NIH, Bethesda, MD 20892 USA.
   [Sacchi, Claudio T.] Inst Adolfo Lutz Registro, Dept Immunol, Sao Paulo, Brazil.
   [Harrison, Lee H.] Univ Pittsburgh, Infect Dis Epidemiol Res Unit, Pittsburgh, PA USA.
RP de Filippis, I (reprint author), Oswaldo Cruz Fdn FIOCRUZ, Natl Qual Control Inst INCQS, Rio De Janeiro, Brazil.
EM rprevots@niaid.nih.gov
FU Division of Intramural Research; Office of Global Research; National
   Institute of Allergy and Infectious Disease (NIAID), National Institutes
   of Health (NIH) [N01-AI30071]; Center for Biologics Evaluation and
   Research (CBER), Food and Drug Administration (FDA); NIAID [K24
   AI52788]; Fogarty International Center, NIH [D43TW006592]; Fundacao de
   Amparo a Pesquisa (FAPESP) [07/00462-3]; Sanofi Pasteur; Novartis;
   Merck; Wyeth; GlaxoSmithKline
FX This work was supported by the Division of Intramural Research, and the
   Office of Global Research, the National Institute of Allergy and
   Infectious Disease (NIAID), National Institutes of Health (NIH); the
   Center for Biologics Evaluation and Research (CBER), Food and Drug
   Administration (FDA); a career development award to Dr. Harrison, NIAID
   (K24 AI52788); a Fogarty International Center Global Infectious Diseases
   Research Training Program grant, NIH, to the University of Pittsburgh
   (D43TW006592); and by a grant from the Fundacao de Amparo a Pesquisa
   (FAPESP), to Sao Paulo, Brazil (07/00462-3). Microbial sequencing was
   supported through a contract to the J. Craig Venter Institute
   (N01-AI30071) from NIAID, NIH. Ivano de Filippis was a postdoctoral
   fellow at the NIH and FDA at the time this work was conducted. The
   funders had no role in study design, data collection and analysis,
   decision to publish, or preparation of the manuscript.; Dr. Harrison
   receives research funding from Sanofi Pasteur; he has received
   consulting fees and speaking honoraria from Sanofi Pasteur, Novartis,
   Merck, Wyeth, and GlaxoSmithKline. This does not alter the authors'
   adherence to all the PLoS ONE policies on sharing data and materials.
   None of the other authors have competing interests.
NR 39
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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 MAR 14
PY 2012
VL 7
IS 3
AR e33016
DI 10.1371/journal.pone.0033016
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 931EO
UT WOS:000303198600037
PM 22431994
ER

PT J
AU Yang, HT
   Ko, MSH
AF Yang, Hsih-Te
   Ko, Minoru S. H.
TI Stochastic Modeling for the Expression of a Gene Regulated by Competing
   Transcription Factors
SO PLOS ONE
LA English
DT Article
ID POSITIVE FEEDBACK; ESCHERICHIA-COLI; CELL FATE; NOISE; INDUCTION;
   MOLECULE; KINETICS; BINARY; SWITCH; LEVEL
AB It is widely accepted that gene expression regulation is a stochastic event. The common approach for its computer simulation requires detailed information on the interactions of individual molecules, which is often not available for the analyses of biological experiments. As an alternative approach, we employed a more intuitive model to simulate the experimental result, the Markov-chain model, in which a gene is regulated by activators and repressors, which bind the same site in a mutually exclusive manner. Our stochastic simulation in the presence of both activators and repressors predicted a Hill-coefficient of the dose-response curve closer to the experimentally observed value than the calculated value based on the simple additive effects of activators alone and repressors alone. The simulation also reproduced the heterogeneity of gene expression levels among individual cells observed by Fluorescence Activated Cell Sorting analysis. Therefore, our approach may help to apply stochastic simulations to broader experimental data.
C1 [Yang, Hsih-Te; Ko, Minoru S. H.] NIA, Dev Genom & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA.
RP Yang, HT (reprint author), NIA, Dev Genom & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA.
EM ko.minoru1@gmail.com
RI Ko, Minoru/B-7969-2009
OI Ko, Minoru/0000-0002-3530-3015
FU National Institutes of Health (NIA)
FX This work was supported entirely by the Intramural Program of the
   National Institutes of Health (NIA). The funders had no role in study
   design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
NR 37
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U1 0
U2 15
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 MAR 14
PY 2012
VL 7
IS 3
AR e32376
DI 10.1371/journal.pone.0032376
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 931EO
UT WOS:000303198600016
PM 22431973
ER

PT J
AU Tsukiyama, T
   Yamaguchi, TP
AF Tsukiyama, Tadasuke
   Yamaguchi, Terry P.
TI Mice lacking Wnt2b are viable and display a postnatal olfactory bulb
   phenotype
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE Wnt; Embryogenesis; Brain; Redundancy; Olfactory bulb
ID PROGENITOR CELLS; CEREBRAL-CORTEX; EXPRESSION; GENES; MOUSE;
   DIFFERENTIATION; IDENTIFICATION; INDUCTION; PROTEINS; EMBRYOS
AB Wnts are secreted glycoproteins that play important roles in embryonic development. Wnt2b is transiently expressed in the primitive streak (PS) during gastrulation and in several organs during organogenesis. To determine the biological function of Wnt2b during mouse development, we established a conditional null allele of Wnt2b. Mice lacking Wnt2b were viable, fertile, and displayed a normal life span, however, the olfactory bulb in adult Wnt2b mutant mice was significantly reduced in length. Our results suggest that Wnt2b primarily plays a supportive role in gastrulation and organogenesis, functioning redundantly with canonical Wnts, such as Wnt2, in numerous tissues. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Tsukiyama, Tadasuke] Hokkaido Univ, Dept Biochem, Grad Sch Med, Kita Ku, Sapporo, Hokkaido 0608638, Japan.
   [Tsukiyama, Tadasuke; Yamaguchi, Terry P.] NCI, Ctr Canc Res, Canc & Dev Biol Lab, Cell Signaling Vertebrate Dev Sect,NIH, Frederick, MD 21702 USA.
RP Tsukiyama, T (reprint author), Hokkaido Univ, Dept Biochem, Grad Sch Med, Kita Ku, N15,W7, Sapporo, Hokkaido 0608638, Japan.
EM tsukit@med.hokudai.ac.jp
RI Tsukiyama, Tadasuke/D-7589-2012
FU NIH, National Cancer Institute, Center for Cancer Research [Z01
   BC010345-08, Z01 BC010841-01]; JSPS at NIH [70216]
FX We thank Kristin K. Bins for laboratory management, Cheri A. Rhoderick
   for administrative assistance and Dr. Sawamoto for comments on the
   manuscript. We also thank Serguei Kozlov and Jaime Greear for embryonic
   engineering and maintenance of mice. This work was supported by the
   Intramural Research Program of the NIH, National Cancer Institute,
   Center for Cancer Research Z01 BC010345-08 and Z01 BC010841-01 (to T. P.
   Y.) and by a JSPS Research Fellowship for Japanese Biomedical and
   Behavioral Researchers at NIH 70216 (to T. T.).
NR 28
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Z9 11
U1 0
U2 3
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0304-3940
J9 NEUROSCI LETT
JI Neurosci. Lett.
PD MAR 14
PY 2012
VL 512
IS 1
BP 48
EP 52
DI 10.1016/j.neulet.2012.01.062
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 921XX
UT WOS:000302512500010
PM 22326927
ER

PT J
AU Zhu, JQ
   Choi, WS
   McCoy, JG
   Negri, A
   Zhu, JH
   Naini, S
   Li, JH
   Shen, M
   Huang, WW
   Bougie, D
   Rasmussen, M
   Aster, R
   Thomas, CJ
   Filizola, M
   Springer, TA
   Coller, BS
AF Zhu, Jieqing
   Choi, Won-Seok
   McCoy, Joshua G.
   Negri, Ana
   Zhu, Jianghai
   Naini, Sarasija
   Li, Jihong
   Shen, Min
   Huang, Wenwei
   Bougie, Daniel
   Rasmussen, Mark
   Aster, Richard
   Thomas, Craig J.
   Filizola, Marta
   Springer, Timothy A.
   Coller, Barry S.
TI Structure-Guided Design of a High-Affinity Platelet Integrin
   alpha(IIb)beta(3) Receptor Antagonist That Disrupts Mg2+ Binding to the
   MIDAS
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID EPTIFIBATIDE-INDUCED THROMBOCYTOPENIA; GLYCOPROTEIN IIB/IIIA
   ANTAGONISTS; ACUTE MYOCARDIAL-INFARCTION; GPIIB/IIIA ANTAGONISTS;
   CONFORMATIONAL-CHANGES; FIBRINOGEN BINDING; PRIMARY PCI; IIB-IIIA;
   RECOGNITION; ACTIVATION
AB An integrin found on platelets, alpha(IIb)beta(3) mediates platelet aggregation, and alpha(IIb)beta(3) antagonists are effective antithrombotic agents in the clinic. Ligands bind to integrins in part by coordinating a magnesium ion (Mg2+) located in the beta subunit metal ion-dependent adhesion site (MIDAS). Drugs patterned on the integrin ligand sequence Arg-Gly-Asp have a basic moiety that binds the alpha(IIb) subunit and a carboxyl group that coordinates the MIDAS Mg2+ in the beta(3) subunits. They induce conformational changes in the beta(3) subunit that may have negative consequences such as exposing previously hidden epitopes and inducing the active conformation of the receptor. We recently reported an inhibitor of alpha(IIb)beta(3) (RUC-1) that binds exclusively to the alpha(IIb) subunit; here, we report the structure-based design and synthesis of RUC-2, a RUC-1 derivative with a similar to 100-fold higher affinity. RUC-2 does not induce major conformational changes in beta(3) as judged by monoclonal antibody binding, light scattering, gel chromatography, electron microscopy, and a receptor priming assay. X-ray crystallography of the RUC-2-alpha(IIb)beta(3) headpiece complex in 1 mM calcium ion (Ca2+)/5 mM Mg2+ at 2.6 angstrom revealed that RUC-2 binds to aIIb the way RUC-1 does, but in addition, it binds to the beta(3) MIDAS residue glutamic acid 220, thus displacing Mg2+ from the MIDAS. When the Mg2+ concentration was increased to 20 mM, however, Mg2+ was identified in the MIDAS and RUC-2 was absent. RUC-2's ability to inhibit ligand binding and platelet aggregation was diminished by increasing the Mg2+ concentration. Thus, RUC-2 inhibits ligand binding by a mechanism different from that of all other alpha(IIb)beta(3) antagonists and may offer advantages as a therapeutic agent.
C1 [Choi, Won-Seok; Naini, Sarasija; Li, Jihong; Coller, Barry S.] Rockefeller Univ, Lab Blood & Vasc Biol, New York, NY 10065 USA.
   [Zhu, Jieqing; Zhu, Jianghai; Springer, Timothy A.] Harvard Univ, Sch Med, Childrens Hosp Boston, Immune Dis Inst, Boston, MA 02115 USA.
   [Zhu, Jieqing; Zhu, Jianghai; Springer, Timothy A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   [Zhu, Jieqing; Bougie, Daniel; Rasmussen, Mark; Aster, Richard] Med Coll Wisconsin, BloodCtr Wisconsin, Milwaukee, WI 53201 USA.
   [McCoy, Joshua G.; Shen, Min; Huang, Wenwei; Thomas, Craig J.] NIH, NIH Chem Genom Ctr, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
   [Negri, Ana; Filizola, Marta] Mt Sinai Sch Med, Dept Struct & Chem Biol, New York, NY 10029 USA.
RP Coller, BS (reprint author), Rockefeller Univ, Lab Blood & Vasc Biol, New York, NY 10065 USA.
EM collerb@rockefeller.edu
FU National Heart, Lung, and Blood Institute [HL19278, HL13629, HL48675];
   National Center for Research Resources, NIH [ULRR024143]; Molecular
   Libraries Initiative of the NIH Roadmap for Medical Research; National
   Human Genome Research Institute; Stony Brook University; National
   Research Foundation of Korea; Korean Government [NRF-2009-352-E00042];
   NSF by Texas Advanced Computing Center [TG-MCB080109N]
FX Funding: Supported, in part, by grants HL19278, HL13629, and HL48675
   from the National Heart, Lung, and Blood Institute; Clinical and
   Translational Science Award grant ULRR024143 from the National Center
   for Research Resources, NIH; the Molecular Libraries Initiative of the
   NIH Roadmap for Medical Research and the Intramural Research Program of
   the National Human Genome Research Institute; funds from Stony Brook
   University; and the National Research Foundation of Korea Grant funded
   by the Korean Government (NRF-2009-352-E00042). The computations were
   supported in part by the NSF through TeraGrid advanced computing
   resources provided by Texas Advanced Computing Center under grant
   TG-MCB080109N (principal investigator: M.F.).
NR 54
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U1 2
U2 20
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 MAR 14
PY 2012
VL 4
IS 125
AR 125ra32
DI 10.1126/scitranslmed.3003576
PG 13
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 909BY
UT WOS:000301538300007
PM 22422993
ER

PT J
AU Chan, T
   Back, TC
   Subleski, JJ
   Weiss, JM
   Ortaldo, JR
   Wiltrout, RH
AF Chan, Tim
   Back, Timothy C.
   Subleski, Jeffrey J.
   Weiss, Jonathan M.
   Ortaldo, John R.
   Wiltrout, Robert H.
TI Systemic IL-12 Administration Alters Hepatic Dendritic Cell Stimulation
   Capabilities
SO PLOS ONE
LA English
DT Article
ID CD8(+) T-CELLS; IN-VIVO; IMMUNE-RESPONSES; NK CELLS; ANTITUMOR IMMUNITY;
   ADAPTIVE IMMUNITY; NATURAL-KILLER; MOUSE-LIVER; GM-CSF; INTERLEUKIN-12
AB The liver is an immunologically unique organ containing tolerogenic dendritic cells (DC) that maintain an immunosuppressive microenvironment. Although systemic IL-12 administration can improve responses to tumors, the effects of IL-12-based treatments on DC, in particular hepatic DC, remain incompletely understood. In this study, we demonstrate systemic IL-12 administration induces a 2-3 fold increase in conventional, but not plasmacytoid, DC subsets in the liver. Following IL-12 administration, hepatic DC became more phenotypically and functionally mature, resembling the function of splenic DC, but differed as compared to their splenic counterparts in the production of IL-12 following co-stimulation with toll-like receptor (TLR) agonists. Hepatic DCs from IL-12 treated mice acquired enhanced T cell proliferative capabilities similar to levels observed using splenic DCs. Furthermore, IL-12 administration preferentially increased hepatic T cell activation and IFN gamma expression in the RENCA mouse model of renal cell carcinoma. Collectively, the data shows systemic IL-12 administration enables hepatic DCs to overcome at least some aspects of the inherently suppressive milieu of the hepatic environment that could have important implications for the design of IL-12-based immunotherapeutic strategies targeting hepatic malignancies and infections.
C1 [Chan, Tim; Back, Timothy C.; Subleski, Jeffrey J.; Weiss, Jonathan M.; Ortaldo, John R.; Wiltrout, Robert H.] Natl Canc Inst, Natl Inst Hlth, Expt Immunol Lab, Canc & Inflammat Program,Ctr Canc Res, Frederick, MD 21702 USA.
RP Wiltrout, RH (reprint author), Natl Canc Inst, Natl Inst Hlth, Expt Immunol Lab, Canc & Inflammat Program,Ctr Canc Res, Frederick, MD 21702 USA.
EM wiltrour@mail.nih.gov
FU National Cancer Institute, National Institutes of Health (NCI/NIH)
FX This work was supported by the Intramural Research Program of the
   National Cancer Institute, National Institutes of Health (NCI/NIH). The
   funders had no role in study design, data collection and analysis,
   decision to publish, or preparation of the manuscript.
NR 51
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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 MAR 13
PY 2012
VL 7
IS 3
AR e33303
DI 10.1371/journal.pone.0033303
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 930IA
UT WOS:000303129700049
PM 22428016
ER

PT J
AU Weinrich, M
   Nanda, H
   Worcester, DL
   Majkrzak, CF
   Maranville, BB
   Bezrukov, SM
AF Weinrich, Michael
   Nanda, Hirsh
   Worcester, David L.
   Majkrzak, Charles F.
   Maranville, Brian B.
   Bezrukov, Sergey M.
TI Halothane Changes the Domain Structure of a Binary Lipid Membrane
SO LANGMUIR
LA English
DT Article
ID X-RAY-SCATTERING; GENERAL-ANESTHESIA; GRAMICIDIN CHANNELS; MODEL
   MEMBRANE; PACKING STRESS; PHASE-DIAGRAM; HIGH-PRESSURE; BILAYERS;
   MIXTURES; ANGLE
AB X-ray and neutron diffraction studies of a binary lipid membrane demonstrate that halothane at physiological concentrations produces a pronounced redistribution of lipids between domains of different lipid types identified by different lamellar d-spacings and isotope composition. In contrast, dichlorohexafluorocyclobutane (F6), a halogenated nonanesthetic, does not produce such significant effects. These findings demonstrate a specific effect of inhalational anesthetics on mixing phase equilibria of a lipid mixture.
C1 [Weinrich, Michael] Eunice Kennedy Shriver Inst Child Hlth & Human De, Natl Ctr Med Rehabil Res, Bethesda, MD USA.
   [Bezrukov, Sergey M.] Eunice Kennedy Shriver Inst Child Hlth & Human De, Sect Mol Transport, Program Phys Biol, Bethesda, MD USA.
   [Nanda, Hirsh; Worcester, David L.; Majkrzak, Charles F.; Maranville, Brian B.] NIST, Ctr Neutron Res, Gaithersburg, MD 20899 USA.
   [Worcester, David L.] Univ Calif Irvine, Dept Physiol & Biophys, Irvine, CA 92717 USA.
   [Worcester, David L.] Univ Missouri, Div Biol, Columbia, MO USA.
RP Weinrich, M (reprint author), Eunice Kennedy Shriver Inst Child Hlth & Human De, Natl Ctr Med Rehabil Res, Bethesda, MD USA.
EM Mw287k@nih.gov
FU NIH; Eunice Kennedy Shriver National Institute of Child Health and Human
   Development; U.S. National Institute of Health [GM86685]
FX We thank Jens Lundbaek and Horia Petrache for fruitful discussions, and
   David Sandstrom for the generous use of his gas chromatograph. This
   study was supported by the NIH Intramural Research Program, Eunice
   Kennedy Shriver National Institute of Child Health and Human
   Development. D.W. was supported by U.S. National Institute of Health
   Grant GM86685 (to Stephen H. White). The Center for Neutron Research
   provided facilities for neutron and X-ray diffraction. We thank Taner
   Yildirim and Jason Simmons for assistance with X-ray measurements. The
   identification of any commercial product or trade name does not imply
   any endorsement or recommendation by the National Institute of Standards
   and Technology.
NR 47
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Z9 17
U1 2
U2 22
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0743-7463
J9 LANGMUIR
JI Langmuir
PD MAR 13
PY 2012
VL 28
IS 10
BP 4723
EP 4728
DI 10.1021/la204317k
PG 6
WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science,
   Multidisciplinary
SC Chemistry; Materials Science
GA 907DD
UT WOS:000301397100016
PM 22352350
ER

PT J
AU Finkel, T
AF Finkel, Toren
TI From Sulfenylation to Sulfhydration: What a Thiolate Needs to Tolerate
SO SCIENCE SIGNALING
LA English
DT Article
ID TYROSINE-PHOSPHATASE 1B; ENDOPLASMIC-RETICULUM STRESS;
   HYDROGEN-PEROXIDE; SIGNAL-TRANSDUCTION; OXIDATION; H2S; INACTIVATION;
   VASORELAXANT; GENERATION; CYSTEINE
AB There is a growing appreciation that oxidants such as hydrogen peroxide (H2O2) and gasses such as nitric oxide (NO) and hydrogen sulfide (H2S) can act as modulators of various signaling pathways. Much of this signaling occurs through the modifications of specific, critical cysteine residues in target proteins. How such small diffusible molecules (H2O2, NO, H2S) can achieve the required specificity is incompletely understood. Now, new findings provide considerable insight into these and related questions.
C1 NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA.
RP Finkel, T (reprint author), NHLBI, Ctr Mol Med, NIH, Bldg 10,CRC 5-3330,10 Ctr Dr, Bethesda, MD 20892 USA.
EM finkelt@nih.gov
FU NIH
FX I am grateful to members of my laboratory for helpful suggestions and to
   I. Rovira for assistance with the manuscript. Funding: This work was
   supported by NIH Intramural funds.
NR 28
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Z9 43
U1 0
U2 9
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1937-9145
J9 SCI SIGNAL
JI Sci. Signal.
PD MAR 13
PY 2012
VL 5
IS 215
AR pe10
DI 10.1126/scisignal.2002943
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 907XG
UT WOS:000301452300003
PM 22416275
ER

PT J
AU Techtmann, SM
   Ghirlando, R
   Kao, S
   Strebel, K
   Maynard, EL
AF Techtmann, Stephen M.
   Ghirlando, Rodolfo
   Kao, Sandra
   Strebel, Klaus
   Maynard, Ernest L.
TI Hydrodynamic and Functional Analysis of HIV-1 Vif Oligomerization
SO BIOCHEMISTRY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; E3 UBIQUITIN LIGASE; PROTEIN SECONDARY
   STRUCTURE; DICHROISM SPECTROSCOPIC DATA; TYPE-1 VIF; CIRCULAR-DICHROISM;
   HUMAN APOBEC3G; SOCS-BOX; SEDIMENTATION-VELOCITY; VIRAL INFECTIVITY
AB HIV-1 Vif is an accessory protein that induces the proteasomal degradation of the host restriction factor, apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G). The N-terminal half of Vif binds to APOBEC3G, and the C-terminal half binds to subunits of a cullin 5-based ubiquitin ligase. This Vif-directed ubiquitin ligase induces the degradation of APOBEC3G (a cytidine deaminase) and thereby protects the viral genome from mutation. A conserved PPLP motif near the C-terminus of Vif is essential for Vif function and is also involved in Vif oligomerization. However, the mechanism and functional significance of Vif oligomerization is unclear. We employed analytical ultracentrifugation to examine the oligomeric properties of Vif in solution. Contrary to previous reports, we find that Vif oligomerization does not require the conserved PPLP motif Instead, our data suggest a more complex mechanism involving interactions among the HCCH motif, the BC box, and downstream residues in Vif Mutation of residues near the PPLP motif (S165 and V166) affected the oligomeric properties of Vif and weakened the ability of Vif to bind and induce the degradation of APOBEC3G. We propose that Vif oligomerization may represent a mechanism for regulating interactions with APOBEC3G.
C1 [Techtmann, Stephen M.; Maynard, Ernest L.] Uniformed Serv Univ Hlth Sci, Dept Biochem & Mol Biol, Bethesda, MD 20814 USA.
   [Ghirlando, Rodolfo] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
   [Kao, Sandra; Strebel, Klaus] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
RP Maynard, EL (reprint author), Uniformed Serv Univ Hlth Sci, Dept Biochem & Mol Biol, Bethesda, MD 20814 USA.
EM emaynard@usuhs.mil
FU Edward Mallinckrodt Jr. Foundation; National Institute of Allergy and
   Infectious Diseases; National Institute of Diabetes and Digestive and
   Kidney Diseases
FX This work was supported by the Edward Mallinckrodt Jr. Foundation
   (E.L.M. and S.M.T.), the National Institutes of Health Intramural
   Research Programs of the National Institute of Allergy and Infectious
   Diseases (K.S. and S.K.), and the National Institute of Diabetes and
   Digestive and Kidney Diseases (R.G.).
NR 69
TC 8
Z9 8
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 MAR 13
PY 2012
VL 51
IS 10
BP 2078
EP 2086
DI 10.1021/bi201738a
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 907DM
UT WOS:000301398000006
PM 22369580
ER

PT J
AU Bambha, K
   Pierce, C
   Cox, C
   French, AL
   Tien, PC
   Sharp, GB
   Augenbraun, M
   Glesby, MJ
   Villacres, MC
   Plankey, M
   Strickler, HD
   Gange, SJ
   Peters, MG
AF Bambha, Kiran
   Pierce, Christopher
   Cox, Christopher
   French, Audrey L.
   Tien, Phyllis C.
   Sharp, Gerald B.
   Augenbraun, Michael
   Glesby, Marshall J.
   Villacres, Maria C.
   Plankey, Michael
   Strickler, Howard D.
   Gange, Stephen J.
   Peters, Marion G.
TI Assessing mortality in women with hepatitis C virus and HIV using
   indirect markers of fibrosis
SO AIDS
LA English
DT Article
DE fibrosis markers; hepatitis C virus; HIV; longitudinal study; mortality
ID HUMAN-IMMUNODEFICIENCY-VIRUS; SIMPLE NONINVASIVE INDEX; LIVER FIBROSIS;
   ANTIRETROVIRAL THERAPY; COINFECTED PATIENTS; VIRAL-HEPATITIS; INFECTION;
   VARIABILITY; PROGRESSION; PREDICTION
AB Objective: Co-infection with hepatitis C virus (HCV) is a major cause of morbidity and mortality in HIV-infected individuals. However, predictors of mortality are poorly defined and most studies have focused predominantly on co-infection in men. We evaluated whether two indirect markers of hepatic fibrosis, aspartate aminotransferase-to-platelet ratio index (APRI) and FIB-4 scores, were predictive of mortality in a well defined longitudinal cohort of HCV/HIV-co-infected women on HAART.
   Methods: HCV/HIV-co-infected women on antiretroviral therapy enrolled in Women's Interagency HIV Study (WIHS), a National Institutes of Health-funded prospective, multicenter, cohort study of women with and at risk for HIV infection were included. Using Cox regression analysis, associations between APRI and FIB-4 with all-cause mortality were assessed.
   Results: Four hundred and fifty HCV/HIV-co-infected women, of whom 191 women died, had a median follow-up of 6.6 years and 5739 WIHS visits. Compared with women with low APRI or FIB-4 levels, severe fibrosis was significantly associated with an increased risk of all-cause mortality {APRI: hazard ratio 2.78 [95% confidence interval (CI) 1.87, 4.12]; FIB-4: hazard ratio 2.58 (95% CI 1.68, 3.95)}. Crude death rates per 1000 patient-years increased with increasing liver fibrosis: 34.8 for mild, 51.3 for moderate and 167.9 for severe fibrosis as measured by FIB-4. Importantly, both APRI and FIB-4 increased during the 5 years prior to death for all women: the slope of increase was greater for women dying a liver-related death compared with nonliver-related death.
   Conclusion: Both APRI and FIB-4 are independently associated with all-cause mortality in HCV/HIV-co-infected women and may have clinical prognostic utility among women with HIV and HCV. (C) 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins
C1 [Peters, Marion G.] Univ Calif San Francisco, Div Gastroenterol, San Francisco, CA 94143 USA.
   [Pierce, Christopher; Cox, Christopher; Gange, Stephen J.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
   [French, Audrey L.] Stroger Hosp, CORE Ctr, Chicago, IL USA.
   [Sharp, Gerald B.] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA.
   [Augenbraun, Michael] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA.
   [Glesby, Marshall J.] Weill Cornell Med Coll, New York, NY USA.
   [Villacres, Maria C.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
   [Plankey, Michael] Georgetown Univ, Sch Med, Washington, DC USA.
   [Tien, Phyllis C.] Dept Vet Affairs Med Ctr, San Francisco, CA USA.
   [Strickler, Howard D.] Albert Einstein Coll Med, New York, NY USA.
RP Peters, MG (reprint author), Univ Calif San Francisco, Div Gastroenterol, 513 Parnassus Ave,Box 0538,Room S-357, San Francisco, CA 94143 USA.
EM marion.peters@ucsf.edu
OI Gange, Stephen/0000-0001-7842-512X
FU National Institute of Allergy and Infectious Diseases [UO1-AI-35004,
   UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590];
   National Institute of Child Health and Human Development [UO1-HD-32632];
   National Cancer Institute; National Institute on Drug Abuse; National
   Institute on Deafness and Other Communication Disorders; NIAID [R21
   A1088361, K23 66943]
FX The WIHS is funded by the National Institute of Allergy and Infectious
   Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989,
   UO1-AI-34993, and UO1-AI-42590) and by the National Institute of Child
   Health and Human Development (UO1-HD-32632). The study is co-funded by
   the National Cancer Institute, the National Institute on Drug Abuse and
   the National Institute on Deafness and Other Communication Disorders.;
   M.P. is supported by NIAID R21 A1088361. P.C.T. is supported by NIAID
   K23 66943 and this work is supported with resources and the use of
   facilities at the San Francisco CA Veterans Affairs Medical Center.
NR 25
TC 24
Z9 24
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD MAR 13
PY 2012
VL 26
IS 5
BP 599
EP 607
DI 10.1097/QAD.0b013e32834fa121
PG 9
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 906GN
UT WOS:000301333000009
PM 22156972
ER

PT J
AU Uthman, O
   Mofenson, LM
   Nachega, JB
AF Uthman, Olalekan
   Mofenson, Lynne M.
   Nachega, Jean B.
TI Safety and effectiveness of efavirenz versus nevirapine-based regimens
   in resource-limited settings: evidence, clinical practice and modelling
   projections
SO AIDS
LA English
DT Editorial Material
DE efavirenz; effectiveness; modelling; nevirapine; safety; sub-Saharan
   Africa
ID VIROLOGICAL OUTCOMES; HIV; METAANALYSIS; PREGNANCY; THERAPY; TRIAL
C1 [Uthman, Olalekan] Keele Univ, Fac Hlth Sci, Dept Primary Care Sci, Keele, Staffs, England.
   [Uthman, Olalekan] Univ Ilorin, Dept Community Hlth & Epidemiol, Ilorin, Nigeria.
   [Mofenson, Lynne M.] Ctr Res Mothers & Children, NIH, Bethesda, MD USA.
   [Mofenson, Lynne M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
   [Nachega, Jean B.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA.
   [Nachega, Jean B.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
   [Nachega, Jean B.] Univ Stellenbosch, Dept Med, Cape Town, South Africa.
   [Nachega, Jean B.] Univ Stellenbosch, Ctr Infect Dis, Cape Town, South Africa.
RP Nachega, JB (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Global Dis Epidemiol & Control Program, 615N Wolfe St,Suite W5031, Baltimore, MD 21205 USA.
EM jnachega@jhsph.edu
OI Mofenson, Lynne/0000-0002-2818-9808; Uthman,
   Olalekan/0000-0002-8567-3081
FU PHS HHS [T84HA21652-01-00]; Wellcome Trust
NR 15
TC 2
Z9 2
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD MAR 13
PY 2012
VL 26
IS 5
BP 639
EP 641
DI 10.1097/QAD.0b013e3283509a40
PG 3
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 906GN
UT WOS:000301333000014
PM 22398571
ER

PT J
AU Kuo, L
   Freed, EO
AF Kuo, Lillian
   Freed, Eric O.
TI ARRDC1 as a mediator of microvesicle budding
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Editorial Material
ID TRAFFICKING; MACHINERY; RECEPTOR; PROTEIN; COMPLEX
C1 [Kuo, Lillian; Freed, Eric O.] NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA.
RP Freed, EO (reprint author), NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA.
EM efreed@nih.gov
NR 13
TC 5
Z9 5
U1 1
U2 4
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 MAR 13
PY 2012
VL 109
IS 11
BP 4025
EP 4026
DI 10.1073/pnas.1201441109
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 907OH
UT WOS:000301426700010
PM 22378650
ER

PT J
AU Miao, YL
   Stein, P
   Jefferson, WN
   Padilla-Banks, E
   Williams, CJ
AF Miao, Yi-Liang
   Stein, Paula
   Jefferson, Wendy N.
   Padilla-Banks, Elizabeth
   Williams, Carmen J.
TI Calcium influx-mediated signaling is required for complete mouse egg
   activation
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID CELL-CYCLE RESUMPTION; CA2+ OSCILLATIONS; FERTILIZATION; PROTEIN; SPERM;
   ENTRY; STIMULATION; POLYSPERMY; TRANSIENTS; RESPONSES
AB Mammalian fertilization is accompanied by oscillations in egg cytoplasmic calcium (Ca2+) concentrations that are critical for completion of egg activation. These oscillations are initiated by Ca2+ release from inositol 1,4,5-trisphosphate (IP3)-sensitive intracellular stores. We tested the hypothesis that Ca2+ influx across the plasma membrane was a requisite component of egg activation signaling, and not simply a Ca2+ source for store repletion. Using intracytoplasmic sperm injection (ICSI) and standard in vitro fertilization (IVF), we found that Ca2+ influx was not required to initiate resumption of meiosis II. However, even if multiple oscillations in intracellular Ca2+ occurred, in the absence of Ca2+ influx, the fertilized eggs failed to emit the second polar body, resulting in formation of three pronuclei. Additional experiments using the Ca2+ chelator, BAPTA/AM, demonstrated that Ca2+ influx is sufficient to support polar body emission and pronucleus formation after only a single sperm-induced Ca2+ transient, whereas BAPTA/AM-treated ICSI or fertilized eggs cultured in Ca2+-free medium remained arrested in metaphase II. Inhibition of store-operated Ca2+ entry had no effect on ICSI-induced egg activation, so Ca2+ influx through alternative channels must participate in egg activation signaling. Ca2+ influx appears to be upstream of CaMKII gamma activity because eggs can be parthenogenetically activated with a constitutively active form of CaMKII gamma in the absence of extracellular Ca2+. These results suggest that Ca2+ influx at fertilization not only maintains Ca2+ oscillations by replenishing Ca2+ stores, but also activates critical signaling pathways upstream of CaMKII gamma that are required for second polar body emission.
C1 [Miao, Yi-Liang; Jefferson, Wendy N.; Padilla-Banks, Elizabeth; Williams, Carmen J.] Natl Inst Environm Hlth Sci, Reprod Med Grp, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA.
   [Stein, Paula] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA.
RP Williams, CJ (reprint author), Natl Inst Environm Hlth Sci, Reprod Med Grp, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA.
EM williamsc5@niehs.nih.gov
RI Williams, Carmen/E-2170-2013
OI Williams, Carmen/0000-0001-6440-7086
FU National Institutes of Health, National Institute of Environmental
   Health Sciences [Z01-ES102985]
FX We thank Jurrien Dean (National Institute of Diabetes and Digestive and
   Kidney Diseases) for the mZP2 antibody and Glaxo Smith Kline for the
   gift of Synta66; Jim Putney and Gary Bird (National Institute on
   Environmental Health Sciences) for critical reading of the manuscript
   and advice throughout this project; and Grace Kissling (National
   Institute on Environmental Health Sciences) for assistance with
   statistical analyses. This work was supported by the Intramural Research
   Program of the National Institutes of Health, National Institute of
   Environmental Health Sciences, Grant Z01-ES102985.
NR 33
TC 50
Z9 50
U1 1
U2 16
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 MAR 13
PY 2012
VL 109
IS 11
BP 4169
EP 4174
DI 10.1073/pnas.1112333109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 907OH
UT WOS:000301426700034
PM 22371584
ER

PT J
AU Baik, S
   Mbaziira, M
   Williams, M
   Ogwang, MD
   Kinyera, T
   Emmanuel, B
   Ziegler, JL
   Reynolds, SJ
   Mbulaiteye, SM
AF Baik, Sonya
   Mbaziira, Mike
   Williams, Makeda
   Ogwang, Martin D.
   Kinyera, Tobias
   Emmanuel, Benjamin
   Ziegler, John L.
   Reynolds, Steven J.
   Mbulaiteye, Sam M.
TI A case-control study of Burkitt lymphoma in East Africa: are local
   health facilities an appropriate source of representative controls?
SO INFECTIOUS AGENTS AND CANCER
LA English
DT Article
ID EPSTEIN-BARR-VIRUS; SICKLE-CELL TRAIT; MALARIA; CHILDREN; UGANDA; RISK;
   ANTIBODIES; DISEASE; GHANA
AB Background: We investigated the feasibility and appropriateness of enrolling controls for Burkitt lymphoma (BL) from local health facilities in two regions in Uganda.
   Methods: BL case data were compiled from two local hospitals with capacity to diagnose and treat BL in Northwest and North-central regions of Uganda during 1997 to 2009. Local health facility data were compiled from children attending four representative local health facilities in the two regions over a two week period in May/June 2010. Age and sex patterns of BL cases and children at local facilities were compared and contrasted using frequency tables.
   Results: There were 999 BL cases diagnosed in the study area (92% of all BL cases treated at the hospitals): 64% were from North-central and 36% from North-west region. The mean age of BL cases was 7.0 years (standard deviation [SD] 3.0). Boys were younger than girls (6.6 years versus 7.2 years, P = 0.004) and cases from North-central region were younger than cases from North-west region (6.8 years versus 7.3 years, P = 0.014). There were 1012 children recorded at the four local health facilities: 91% at facilities in North-central region and 9% from facilities in North-west region. Daily attendance varied between 1 to 75 children per day. The mean age of children at health facilities was 2.2 years (SD 2.8); it did not differ by sex. Children at North-central region facilities were younger than children at North-west region facilities (1.8 years versus 6.6 years, P < 0.001).
   Conclusions: While many children attend local health facilities, confirming feasibility of obtaining controls, their mean age is much lower than BL cases. Health facilities may be suitable for obtaining young, but not older, controls.
C1 [Baik, Sonya; Ziegler, John L.] UCSF, Global Hlth Sci, San Francisco, CA USA.
   [Mbaziira, Mike; Ogwang, Martin D.; Kinyera, Tobias] St Marys Hosp Lacor, EMBLEM Study Off, Gulu, Uganda.
   [Williams, Makeda] NCI, Ctr Global Hlth, Bethesda, MD 20892 USA.
   [Ogwang, Martin D.] St Marys Hosp Lacor, Dept Surg, Gulu, Uganda.
   [Emmanuel, Benjamin; Mbulaiteye, Sam M.] NCI, Infect & Immunoepidemiol Branch, Bethesda, MD 20892 USA.
   [Reynolds, Steven J.] NIAID, NIH, Div Intramural Res, Bethesda, MD 20892 USA.
   [Mbulaiteye, Sam M.] NCI, NIH, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet,Infect & Immunoepidemi, Rockville, MD 20852 USA.
RP Mbulaiteye, SM (reprint author), NCI, Infect & Immunoepidemiol Branch, Bethesda, MD 20892 USA.
EM mbulaits@mail.nih.gov
FU Intramural Research Program, Division of Cancer Epidemiology and
   Genetics; National Cancer Institute; National Institute of Allergy and
   Infectious Diseases; National Institutes of Health; Department of Health
   and Human Services
FX Funded by the Intramural Research Program, Division of Cancer
   Epidemiology and Genetics, National Cancer Institute and National
   Institute of Allergy and Infectious Diseases, National Institutes of
   Health, Department of Health and Human Services. We thank the staff of
   St. Mary's Hospital, Lacor, and Kuluva Hospital, as well the staff at
   the local health facilities for their cooperation with the study and
   advice.
NR 28
TC 6
Z9 6
U1 2
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1750-9378
J9 INFECT AGENTS CANCER
JI Infect. Agents Cancer
PD MAR 13
PY 2012
VL 7
AR UNSP 5
DI 10.1186/1750-9378-7-5
PG 6
WC Oncology; Immunology
SC Oncology; Immunology
GA 241FS
UT WOS:000326152400001
PM 22413839
ER

PT J
AU Crane, DD
   Scott, DP
   Bosio, CM
AF Crane, Deborah D.
   Scott, Dana P.
   Bosio, Catharine M.
TI Generation of a Convalescent Model of Virulent Francisella tularensis
   Infection for Assessment of Host Requirements for Survival of Tularemia
SO PLOS ONE
LA English
DT Article
ID LIVE VACCINE STRAIN; LISTERIA-MONOCYTOGENES INFECTION; INNATE
   IMMUNE-RESPONSE; KNOCK-OUT MICE; T-CELL SUBSETS; IFN-GAMMA;
   INTRACELLULAR BACTERIUM; AEROSOL INFECTION; DENDRITIC CELLS;
   RESPIRATORY-INFECTION
AB Francisella tularensis is a facultative intracellular bacterium and the causative agent of tularemia. Development of novel vaccines and therapeutics for tularemia has been hampered by the lack of understanding of which immune components are required to survive infection. Defining these requirements for protection against virulent F. tularensis, such as strain SchuS4, has been difficult since experimentally infected animals typically die within 5 days after exposure to as few as 10 bacteria. Such a short mean time to death typically precludes development, and therefore assessment, of immune responses directed against virulent F. tularensis. To enable identification of the components of the immune system that are required for survival of virulent F. tularensis, we developed a convalescent model of tularemia in C57Bl/6 mice using low dose antibiotic therapy in which the host immune response is ultimately responsible for clearance of the bacterium. Using this model we demonstrate alpha bTCR(+) cells, gamma delta TCR+ cells, and B cells are necessary to survive primary SchuS4 infection. Analysis of mice deficient in specific soluble mediators shows that IL-12p40 and IL-12p35 are essential for survival of SchuS4 infection. We also show that IFN-gamma is required for survival of SchuS4 infection since mice lacking IFN-gamma R succumb to disease during the course of antibiotic therapy. Finally, we found that both CD4(+) and CD8(+) cells are the primary producers of IFN-gamma and that gamma delta TCR+ cells and NK cells make a minimal contribution toward production of this cytokine throughout infection. Together these data provide a novel model that identifies key cells and cytokines required for survival or exacerbation of infection with virulent F. tularensis and provides evidence that this model will be a useful tool for better understanding the dynamics of tularemia infection.
C1 [Crane, Deborah D.; Bosio, Catharine M.] NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT USA.
   [Scott, Dana P.] NIAID, Vet Pathol Sect, Rocky Mt Vet Branch, Rocky Mt Labs,NIH, Hamilton, MT USA.
RP Crane, DD (reprint author), NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT 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. The funders had no role in study design, data
   collection and analysis, decision to publish, or preparation of the
   manuscript.
NR 90
TC 19
Z9 19
U1 1
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 MAR 12
PY 2012
VL 7
IS 3
AR e33349
DI 10.1371/journal.pone.0033349
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 920DF
UT WOS:000302381500130
PM 22428026
ER

PT J
AU Lim, S
   Bae, E
   Kim, HS
   Kim, TA
   Byun, K
   Kim, B
   Hong, S
   Im, JP
   Yun, C
   Lee, B
   Lee, B
   Park, SH
   Letterio, J
   Kim, SJ
AF Lim, Seunghwan
   Bae, Eunjin
   Kim, Hae-Suk
   Kim, Tae-Aug
   Byun, Kyunghee
   Kim, Byungchul
   Hong, Suntaek
   Im, Jong Pil
   Yun, Chohee
   Lee, Bona
   Lee, Bonghee
   Park, Seok Hee
   Letterio, John
   Kim, Seong-Jin
TI TRAF6 Mediates IL-1 beta/LPS-Induced Suppression of TGF-beta Signaling
   through Its Interaction with the Type III TGF-beta Receptor
SO PLOS ONE
LA English
DT Article
ID GROWTH-FACTOR-BETA; NF-KAPPA-B; TRANSCRIPTIONAL REGULATION; INDEPENDENT
   ACTIVATION; HEPATOMA-CELLS; CANCER; GENE; DIFFERENTIATION;
   POLYMORPHISMS; INFLAMMATION
AB Transforming growth factor-beta 1 (TGF-beta 1) is an important anti-inflammatory cytokine that modulates and resolves inflammatory responses. Recent studies have demonstrated that inflammation enhances neoplastic risk and potentiates tumor progression. In the evolution of cancer, pro-inflammatory cytokines such as IL-1 beta must overcome the anti-inflammatory effects of TGF-beta to boost pro-inflammatory responses in epithelial cells. Here we show that IL-1 beta or Lipopolysaccharide (LPS) suppresses TGF-beta-induced anti-inflammatory signaling in a NF-kappa B-independent manner. TRAF6, a key molecule in IL-1 beta signaling, mediates this suppressive effect through interaction with the type III TGF-beta receptor (T beta RIII), which is TGF-beta-dependent and requires type I TGF-beta receptor (T beta RI) kinase activity. T beta RI phosphorylates T beta RIII at residue S829, which promotes the TRAF6/T beta RIII interaction and consequent sequestration of T beta RIII from the T beta RII/T beta RI complex. Our data indicate that IL-1 beta enhances the pro-inflammatory response by suppressing TGF-beta signaling through TRAF6-mediated sequestration of T beta RIII, which may be an important contributor to the early stages of tumor progression.
C1 [Lim, Seunghwan; Kim, Hae-Suk; Im, Jong Pil; Yun, Chohee; Lee, Bona; Letterio, John; Kim, Seong-Jin] Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA.
   [Bae, Eunjin; Lee, Bona; Kim, Seong-Jin] CHA Univ, CHA Canc Inst, Seoul, South Korea.
   [Bae, Eunjin; Byun, Kyunghee; Hong, Suntaek; Lee, Bonghee; Kim, Seong-Jin] Gachon Univ Med & Sci, Lee Gil Ya Canc & Diabet Inst, Songdo, Incheon, South Korea.
   [Kim, Tae-Aug] NCI, Lab Canc & Stem Cell Biol, Bethesda, MD 20892 USA.
   [Kim, Byungchul] Kangwon Natl Univ, Coll Nat Sci, Dept Biochem, Chunchon, South Korea.
   [Im, Jong Pil] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea.
   [Im, Jong Pil] Seoul Natl Univ, Coll Med, Liver Res Inst, Seoul, South Korea.
   [Park, Seok Hee] Sungkyunkwan Univ, Dept Mol Biol, Suwon, South Korea.
RP Lim, S (reprint author), Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA.
EM kimsj@cha.ac.kr
FU National Research Foundation of Korea [20090081756]; Korea Science and
   Engineering Foundation (KOSEF) [ROA-2007-000-20047-0]
FX This work is supported in part by grants from National Research
   Foundation of Korea (Bio Technology Research & Development Program
   20090081756 to S-JK, SH and SHP) and from Korea Science and Engineering
   Foundation (KOSEF) (ROA-2007-000-20047-0 to SHP). 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 34
TC 5
Z9 5
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 MAR 12
PY 2012
VL 7
IS 3
AR e32705
DI 10.1371/journal.pone.0032705
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 920DF
UT WOS:000302381500035
PM 22427868
ER

PT J
AU Simon-Sanchez, J
   Kilarski, LL
   Nalls, MA
   Martinez, M
   Schulte, C
   Holmans, P
   Gasser, T
   Hardy, J
   Singleton, AB
   Wood, NW
   Brice, A
   Heutink, P
   Williams, N
   Morris, HR
AF Simon-Sanchez, Javier
   Kilarski, Laura L.
   Nalls, Michael A.
   Martinez, Maria
   Schulte, Claudia
   Holmans, Peter
   Gasser, Thomas
   Hardy, John
   Singleton, Andrew B.
   Wood, Nicholas W.
   Brice, Alexis
   Heutink, Peter
   Williams, Nigel
   Morris, Huw R.
CA Int Parkinson's Dis Genomics Conso
   Wellcome Trust Case Control Consor
TI Cooperative Genome-Wide Analysis Shows Increased Homozygosity in Early
   Onset Parkinson's Disease
SO PLOS ONE
LA English
DT Article
ID FAMILIAL AGGREGATION; ALZHEIMERS-DISEASE; EXTENDED TRACTS; NO EVIDENCE;
   ASSOCIATION; MUTATIONS; RUNS; METAANALYSIS; PINK1; LOCI
AB Parkinson's disease (PD) occurs in both familial and sporadic forms, and both monogenic and complex genetic factors have been identified. Early onset PD (EOPD) is particularly associated with autosomal recessive (AR) mutations, and three genes, PARK2, PARK7 and PINK1, have been found to carry mutations leading to AR disease. Since mutations in these genes account for less than 10% of EOPD patients, we hypothesized that further recessive genetic factors are involved in this disorder, which may appear in extended runs of homozygosity. We carried out genome wide SNP genotyping to look for extended runs of homozygosity (ROHs) in 1,445 EOPD cases and 6,987 controls. Logistic regression analyses showed an increased level of genomic homozygosity in EOPD cases compared to controls. These differences are larger for ROH of 9 Mb and above, where there is a more than three-fold increase in the proportion of cases carrying a ROH. These differences are not explained by occult recessive mutations at existing loci. Controlling for genome wide homozygosity in logistic regression analyses increased the differences between cases and controls, indicating that in EOPD cases ROHs do not simply relate to genome wide measures of inbreeding. Homozygosity at a locus on chromosome 19p13.3 was identified as being more common in EOPD cases as compared to controls. Sequencing analysis of genes and predicted transcripts within this locus failed to identify a novel mutation causing EOPD in our cohort. There is an increased rate of genome wide homozygosity in EOPD, as measured by an increase in ROHs. These ROHs are a signature of inbreeding and do not necessarily harbour disease-causing genetic variants. Although there might be other regions of interest apart from chromosome 19p13.3, we lack the power to detect them with this analysis.
C1 [Simon-Sanchez, Javier; Heutink, Peter] Vrije Univ Amsterdam, Sect Med Genom, Dept Clin Genet, Med Ctr, Amsterdam, Netherlands.
   [Kilarski, Laura L.; Holmans, Peter; Williams, Nigel; Morris, Huw R.; Wellcome Trust Case Control Consor] Cardiff Univ, Sch Med, MRC Ctr Neuropsychiat Genet & Genom, Cardiff, S Glam, Wales.
   [Nalls, Michael A.; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
   [Martinez, Maria] Fac Med Toulouse, INSERM, UMR 1043, F-31073 Toulouse, France.
   [Martinez, Maria] Univ Toulouse 3, F-31062 Toulouse, France.
   [Kilarski, Laura L.; Holmans, Peter; Williams, Nigel; Morris, Huw R.] Cardiff Univ, Sch Med, Dept Psychol Med & Neurol, Cardiff, S Glam, Wales.
   [Schulte, Claudia; Gasser, Thomas] German Ctr Neurodegenerat Dis, Hertie Inst Clin Brain Res, Dept Neurodegenerat Dis, Tubingen, Germany.
   [Schulte, Claudia; Gasser, Thomas] German Ctr Neurodegenerat Dis, DZNE, Tubingen, Germany.
   [Hardy, John; Wood, Nicholas W.] UCL Inst Neurol, Dept Mol Neurosci, London, England.
   [Brice, Alexis] Univ Paris 06, Ctr Rech, Inst Cerveau & Moelle Epiniere, UMR S975, Paris, France.
   [Brice, Alexis] INSERM, U975, Paris, France.
   [Brice, Alexis] CNRS, UMR 7225, Paris, France.
RP Simon-Sanchez, J (reprint author), Vrije Univ Amsterdam, Sect Med Genom, Dept Clin Genet, Med Ctr, Amsterdam, Netherlands.
EM williamsnm@cf.ac.uk; morrishr@cf.ac.uk
RI Hardy, John/C-2451-2009; Morris, Huw/B-8527-2008; Singleton,
   Andrew/C-3010-2009; Traynor, Bryan/G-5690-2010; Holmans,
   Peter/F-4518-2015; Martinez, Maria/B-3111-2013; Wood,
   Nicholas/C-2505-2009; 
OI Morris, Huw/0000-0002-5473-3774; Holmans, Peter/0000-0003-0870-9412;
   Martinez, Maria/0000-0003-2180-4537; Wood, Nicholas/0000-0002-9500-3348;
   Schulte, Claudia/0000-0003-4006-1265; Kilarski,
   Laura/0000-0003-0645-3134
FU Medical Research Council UK [G0700943]; Parkinson's UK [8047, J-0804];
   National Institute on Aging; Wellcome Trust/MRC [WT089698]; Department
   of Health NIHR Biomedical Research Centre; Wellcome Trust
   [085475/B/08/Z, 085475/Z/08/Z, 068545/Z/02]; Medical Research Council
   [G0000934]; Hersenstichting Nederland; Neuroscience Campus Amsterdam;
   Prinses Beatrix Fonds; Forschungszentrum fur Umwelt und Gesundheit
   (GSF); German Federal Ministry of Education, Science, Research and
   Technology; State of Bavaria; German National Genome Network (NGFNplus;
   German Ministry for Education and Research) [01GS08134]; German Ministry
   for Education and Research; German Federal Ministry of Education and
   Research (BMBF) NGFN [01GR0468]; ERA-Net NEURON [01GW0908]; Helmholtz
   Alliance Mental Health in an Ageing Society (HelMA) [HA-215]; Helmholtz
   Association
FX This work was supported by the Medical Research Council UK (G0700943)
   and Parkinson's UK (Grant 8047 and J-0804). This work was supported in
   part by the Intramural Research Programs of the National Institute on
   Aging and the National Institute of Neurological Disorders and Stroke,
   National Institutes of Health, Department of Health and Human Services;
   project number Z01 AG000949-05. This work was supported in part by the
   Wellcome Trust/MRC Joint Call in Neurodegeneration award (WT089698) to
   the UK Parkinson's Disease Consortium whose members are from the
   UCL/Institute of Neurology, the University of Sheffield and the MRC
   Protein Phosphorylation Unit at the University of Dundee. Additionally,
   part of the study was undertaken at UCLH/UCL using funding through a
   Department of Health NIHR Biomedical Research Centre. We used
   genome-wide association data generated by the Wellcome Trust
   Case-Control Consortium 2 (WTCCC2) from UK patients with Parkinson's
   disease and UK control individuals from the 1958 Birth Cohort and
   National Blood Service. The WTCCC2 project was funded by the Wellcome
   Trust (085475/B/08/Z and 085475/Z/08/Z); the authors acknowledge use of
   the British 1958 Birth Cohort DNA collection funded by the Medical
   Research Council (G0000934) and the Wellcome Trust (068545/Z/02), and of
   the UK National Blood Service controls funded by the Wellcome Trust.
   This study utilized the high-performance computational capabilities of
   the Biowulf Linux cluster at the National Institutes of Health,
   Bethesda, Maryland (http://biowulf.nih.gov). The authors also want to
   thank the Hersenstichting Nederland (http://www.hersenstichting.nl), the
   Neuroscience Campus Amsterdam, and the Prinses Beatrix Fonds
   (http://www.prinsesbeatrixfonds.nl) for sponsoring this work. The KORA
   research platform (KORA: Cooperative Research in the Region of Augsburg;
   http://www.gsf.de/KORA) was initiated and financed by the
   Forschungszentrum fur Umwelt und Gesundheit (GSF), which is funded by
   the German Federal Ministry of Education, Science, Research and
   Technology and by the State of Bavaria. The study was additionally
   funded by the German National Genome Network (NGFNplus #01GS08134;
   German Ministry for Education and Research), and by the German Federal
   Ministry of Education and Research (BMBF) NGFN (01GR0468), and in the
   frame of ERA-Net NEURON (01GW0908). This work was also supported by the
   Helmholtz Alliance Mental Health in an Ageing Society (HelMA, HA-215)
   funded by the Initiative and Networking Fund of the Helmholtz
   Association. The funders had no role in study design, data collection
   and analysis, decision to publish, or preparation of the manuscript.
NR 34
TC 12
Z9 12
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 MAR 12
PY 2012
VL 7
IS 3
AR e28787
DI 10.1371/journal.pone.0028787
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 920DF
UT WOS:000302381500001
PM 22427796
ER

PT J
AU Luo, JH
   Rossouw, J
   Tong, E
   Giovino, GA
   Lee, C
   Chen, C
   Ockene, JK
   Qi, LH
   Margolis, KL
AF Luo, Juhua
   Rossouw, Jacques
   Tong, Elisa
   Giovino, Gary A.
   Lee, Cathy
   Chen, Chu
   Ockene, Judith K.
   Qi, Lihong
   Margolis, Karen L.
TI Smoking Cessation, Weight Gain, and Risk of Type 2 Diabetes Mellitus
   Among Postmenopausal Women
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Letter
ID METAANALYSIS; COHORT
C1 [Luo, Juhua] W Virginia Univ, Dept Community Med, Mary Babb Randolph Canc Ctr, Morgantown, WV 26506 USA.
   [Rossouw, Jacques] NHLBI, NIH, US Dept HHS, Bethesda, MD 20892 USA.
   [Tong, Elisa] Univ Calif, Davis Med Ctr, Div Gen Internal Med, Sacramento, CA USA.
   [Giovino, Gary A.] SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Dept Community Hlth & Hlth Behav, Buffalo, NY 14260 USA.
   [Lee, Cathy] Univ Calif Los Angeles, David Geffen Sch Med, Dept Internal Med, Div Geriatr, Los Angeles, CA 90095 USA.
   [Lee, Cathy] Vet Affairs Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA USA.
   [Chen, Chu] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
   [Ockene, Judith K.] Univ Massachusetts, Sch Med, Worcester, MA USA.
   [Qi, Lihong] Univ Calif Davis, Dept Publ Hlth Sci, Davis, CA 95616 USA.
   [Margolis, Karen L.] HealthPartners Res Fdn, Minneapolis, MN USA.
RP Luo, JH (reprint author), W Virginia Univ, Dept Community Med, Mary Babb Randolph Canc Ctr, Morgantown, WV 26506 USA.
EM Jiluo@hsc.wvu.edu
NR 9
TC 10
Z9 10
U1 1
U2 4
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 MAR 12
PY 2012
VL 172
IS 5
BP 438
EP 440
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 906XB
UT WOS:000301381300017
PM 22412112
ER

PT J
AU Driver, JA
   Beiser, A
   Au, R
   Kreger, BE
   Splansky, GL
   Kurth, T
   Kiel, DP
   Lu, KP
   Seshadri, S
   Wolf, PA
AF Driver, Jane A.
   Beiser, Alexa
   Au, Rhoda
   Kreger, Bernard E.
   Splansky, Greta Lee
   Kurth, Tobias
   Kiel, Douglas P.
   Lu, Kun Ping
   Seshadri, Sudha
   Wolf, Phillip A.
TI Inverse association between cancer and Alzheimer's disease: results from
   the Framingham Heart Study
SO BRITISH MEDICAL JOURNAL
LA English
DT Article
ID PROLYL ISOMERASE PIN1; PARKINSONS-DISEASE; CELL-CYCLE; VASCULAR
   DEMENTIA; RISK; DIAGNOSIS; COHORT; CHEMOTHERAPY; HEALTH; AGE
AB Objectives To relate cancer since entry into the Framingham Heart Study with the risk of incident Alzheimer's disease and to estimate the risk of incident cancer among participants with and without Alzheimer's disease.
   Design Community based prospective cohort study; nested age and sex matched case-control study.
   Setting Framingham Heart Study, USA.
   Participants 1278 participants with and without a history of cancer who were aged 65 or more and free of dementia at baseline (1986-90).
   Main outcome measures Hazard ratios and 95% confidence intervals for the risks of Alzheimer's disease and cancer.
   Results Over a mean follow-up of 10 years, 221 cases of probable Alzheimer's disease were diagnosed. Cancer survivors had a lower risk of probable Alzheimer's disease (hazard ratio 0.67, 95% confidence interval 0.47 to 0.97), adjusted for age, sex, and smoking. The risk was lower among survivors of smoking related cancers (0.26, 0.08 to 0.82) than among survivors of non-smoking related cancers (0.82, 0.57 to 1.19). In contrast with their decreased risk of Alzheimer's disease, survivors of smoking related cancer had a substantially increased risk of stroke (2.18, 1.29 to 3.68). In the nested case-control analysis, participants with probable Alzheimer's disease had a lower risk of subsequent cancer (0.39, 0.26 to 0.58) than reference participants, as did participants with any Alzheimer's disease (0.38) and any dementia (0.44).
   Conclusions Cancer survivors had a lower risk of Alzheimer's disease than those without cancer, and patients with Alzheimer's disease had a lower risk of incident cancer. The risk of Alzheimer's disease was lowest in survivors of smoking related cancers, and was not primarily explained by survival bias. This pattern for cancer is similar to that seen in Parkinson's disease and suggests an inverse association between cancer and neurodegeneration.
C1 [Driver, Jane A.] Ctr Geriatr Res Educ & Clin, Boston, MA 02130 USA.
   [Driver, Jane A.] Boston VA Med Ctr, Boston, MA 02130 USA.
   [Driver, Jane A.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA.
   [Driver, Jane A.; Kurth, Tobias] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
   [Beiser, Alexa; Au, Rhoda; Seshadri, Sudha; Wolf, Phillip A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
   [Beiser, Alexa] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
   [Beiser, Alexa; Kreger, Bernard E.; Splansky, Greta Lee; Wolf, Phillip A.] NHLBI, Framingham Heart Study, Framingham, MA USA.
   [Kreger, Bernard E.] Boston Univ, Dept Med, Boston, MA 02215 USA.
   [Kurth, Tobias] INSERM, Neuroepidemiol U708, Bordeaux, France.
   [Kiel, Douglas P.; Lu, Kun Ping] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA.
RP Driver, JA (reprint author), Ctr Geriatr Res Educ & Clin, Boston, MA 02130 USA.
EM jdriver@partners.org
RI Kurth, Tobias/A-9243-2012; 
OI Kurth, Tobias/0000-0001-7169-2620; Seshadri, Sudha/0000-0001-6135-2622;
   Au, Rhoda/0000-0001-7742-4491; Kiel, Douglas/0000-0001-8474-0310;
   Beiser, Alexa/0000-0001-8551-7778
FU Veterans' Administration; National Heart, Lung, and Blood Institute
   [N01-HC-25195]; National Institutes of Aging [AG16495, AG08122];
   National Institute of Neurological Disorders and Stroke [NS17950]
FX JAD was funded by a Veterans' Administration career development award.
   The Framingham Heart Study is supported by an National Heart, Lung, and
   Blood Institute contract (N01-HC-25195) and by grants from the National
   Institutes of Aging (AG16495 and AG08122) and National Institute of
   Neurological Disorders and Stroke (NS17950). The authors' work was
   independent of the funders. The funders had no role in the design and
   conduct of the study; collection, management, analysis, and
   interpretation of the data; and preparation, review, or approval of the
   manuscript.
NR 52
TC 69
Z9 72
U1 2
U2 14
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1756-1833
J9 BRIT MED J
JI Br. Med. J.
PD MAR 12
PY 2012
VL 344
AR e1442
DI 10.1136/bmj.e1442
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 913BO
UT WOS:000301846500004
PM 22411920
ER

PT J
AU Huang, Y
   Ballinger, DG
   Dai, JY
   Peters, U
   Hinds, DA
   Cox, DR
   Beilharz, E
   Chlebowski, RT
   Rossouw, JE
   McTiernan, A
   Rohan, T
   Prentice, RL
AF Huang, Ying
   Ballinger, Dennis G.
   Dai, James Y.
   Peters, Ulrike
   Hinds, David A.
   Cox, David R.
   Beilharz, Erica
   Chlebowski, Rowan T.
   Rossouw, Jacques E.
   McTiernan, Anne
   Rohan, Thomas
   Prentice, Ross L.
TI Correction: Genetic variants in the MRPS30 region and postmenopausal
   breast cancer risk (vol 4, pg 19, 2012)
SO GENOME MEDICINE
LA English
DT Correction
C1 [Huang, Ying; Dai, James Y.; Peters, Ulrike; McTiernan, Anne; Prentice, Ross L.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
   [Ballinger, Dennis G.; Hinds, David A.; Cox, David R.; Beilharz, Erica] Perlegen Sci Inc, Mountain View, CA 94043 USA.
   [Chlebowski, Rowan T.] Harbor UCLA Res & Educ Inst, Torrance, CA 90502 USA.
   [Rossouw, Jacques E.] NIH, Bethesda, MD 20892 USA.
   [Rohan, Thomas] Albert Einstein Coll Med, Bronx, NY 10461 USA.
RP Prentice, RL (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,M3-A410,POB 19024, Seattle, WA 98109 USA.
EM rprentic@fhcrc.org
NR 2
TC 1
Z9 1
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-994X
J9 GENOME MED
JI Genome Med.
PD MAR 12
PY 2012
VL 4
DI 10.1186/gm318
PG 1
WC Genetics & Heredity
SC Genetics & Heredity
GA 084VJ
UT WOS:000314566900001
PM 22410340
ER

PT J
AU Salit, RB
   Fowler, DH
   Wilson, WH
   Dean, RM
   Pavletic, SZ
   Dunleavy, K
   Hakim, F
   Fry, TJ
   Steinberg, SM
   Hughes, TE
   Odom, J
   Bryant, K
   Gress, RE
   Bishop, MR
AF Salit, Rachel B.
   Fowler, Daniel H.
   Wilson, Wyndham H.
   Dean, Robert M.
   Pavletic, Steven Z.
   Dunleavy, Kieron
   Hakim, Frances
   Fry, Terry J.
   Steinberg, Seth M.
   Hughes, Thomas E.
   Odom, Jeanne
   Bryant, Kelly
   Gress, Ronald E.
   Bishop, Michael R.
TI Dose-Adjusted EPOCH-Rituximab Combined With Fludarabine Provides an
   Effective Bridge to Reduced-Intensity Allogeneic Hematopoietic Stem-Cell
   Transplantation in Patients With Lymphoid Malignancies
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID NON-HODGKINS-LYMPHOMA; SALVAGE THERAPY; PHASE-II; CHEMOTHERAPY; REGIMEN;
   PRETRANSPLANT; CHIMERISM; DEPLETION; OUTCOMES; DISEASE
AB Purpose
   There is currently no standard chemotherapy regimen for patients with lymphoid malignancies being considered for reduced-intensity conditioning allogeneic hematopoietic stem-cell transplantation (RIC-alloHSCT). The ideal regimen would provide disease control and result in lymphocyte depletion to facilitate engraftment. To this end, we developed a novel regimen by adding fludarabine to dose-adjusted continuous-infusion etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus with or without rituximab (DA-EPOCH-F/R).
   Patients and Methods
   One hundred forty-seven patients with lymphoid malignancy (median age, 50 years) who had heavily pretreated (median prior regimens, three) and chemo-refractory (47%) disease were treated with DA-EPOCH-F/R before RIC-alloHSCT. Patients received one to three consecutive cycles until achieving lymphocyte depletion (CD4(+) count <200/mu L) or progressive disease.
   Results
   Overall response rate was 41%; 39% of patients had stable disease. Toxicity included grade 4 neutropenia in 65% and thrombocytopenia in 25% of patients. DA-EPOCH-F/R resulted in lymphocyte depletion (P < .001), which was inversely associated with serum interleukin (IL) 7 and IL-15 levels. Of 147 patients, 143 patients proceeded to RIC-alloHSCT. Patients with lower CD3(+) (P<.001), CD4(+) (P<.001), and CD8(+) (P<.001) T-cell counts after DA-EPOCH-F/R were more likely to achieve full donor lymphoid chimerism by day +14 after transplant. Relative to nonresponders to DA-EPOCH-F/R, patients with complete and partial response had increased event-free survival (77.4 v 4.8 months; P<.001) and overall survival (98.5 v 16.2 months; P<.001).
   Conclusion
   DA-EPOCH-F/R safely provides tumor cytoreduction and lymphocyte depletion, thereby offering a bridge to RIC-alloHSCT in patients with aggressive lymphoid malignancies. J Clin Oncol 30: 830-836. (C) 2012 by American Society of Clinical Oncology
C1 [Salit, Rachel B.; Fowler, Daniel H.; Wilson, Wyndham H.; Pavletic, Steven Z.; Dunleavy, Kieron; Hakim, Frances; Fry, Terry J.; Steinberg, Seth M.; Odom, Jeanne; Bryant, Kelly; Gress, Ronald E.; Bishop, Michael R.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Hughes, Thomas E.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
   [Dean, Robert M.] Cleveland Clin Fdn, Taussig Canc Ctr, Cleveland, OH 44195 USA.
RP Bishop, MR (reprint author), Med Coll Wisconsin, Ctr Clin Canc, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA.
EM mbishop@mcw.edu
FU Center for Cancer Research, National Cancer Institute, National
   Institutes of Health, Bethesda, MD
FX Supported by Center for Cancer Research, National Cancer Institute,
   National Institutes of Health, Bethesda, MD.
NR 35
TC 7
Z9 7
U1 0
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 10
PY 2012
VL 30
IS 8
BP 830
EP 836
DI 10.1200/JCO.2011.37.0296
PG 7
WC Oncology
SC Oncology
GA 923NS
UT WOS:000302626600018
PM 22312100
ER

PT J
AU David, A
   Das, SR
   Gibbs, JS
   Bennink, JR
   Yewdell, JW
AF David, Alexandre
   Das, Suman R.
   Gibbs, James S.
   Bennink, Jack R.
   Yewdell, Jonathan W.
TI Cysteinyl-tRNA Deacylation Can Be Uncoupled from Protein Synthesis
SO PLOS ONE
LA English
DT Article
ID RIBONUCLEIC-ACID SYNTHETASE; IN-VIVO; CELLS; RECOGNITION; TRANSLATION;
   INHIBITION; ABSENCE
AB Aminoacyl-tRNA synthetases (ARSs) are critical components of protein translation, providing ribosomes with aminoacyl-tRNAs. In return, ribosomes release uncharged tRNAs as ARS substrates. Here, we show that tRNA deacylation can be uncoupled from protein synthesis in an amino acid specific manner. While tRNAs coupled to radiolabeled Met, Leu Lys, or Ser are stable in cells following translation inhibition with arsenite, radiolabeled Cys is released from tRNA at a high rate. We discuss possible translation independent functions for tRNA(Cys).
C1 [David, Alexandre; Das, Suman R.; Gibbs, James S.; Bennink, Jack R.; Yewdell, Jonathan W.] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
RP David, A (reprint author), NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
EM jyewdell@nih.gov
RI Das, Suman/C-8760-2009; David, Alexandre/B-2447-2013
OI David, Alexandre/0000-0003-3365-1339
FU Division of Intramural Research, National Institute of Allergy and
   Infectious Diseases
FX This work was generously supported by the Division of Intramural
   Research, National Institute of Allergy and Infectious Diseases. The
   funders had no role in study design, data collection and analysis,
   decision to publish, or preparation of the manuscript.
NR 20
TC 1
Z9 1
U1 0
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 MAR 9
PY 2012
VL 7
IS 3
AR e33072
DI 10.1371/journal.pone.0033072
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 929KX
UT WOS:000303062800042
PM 22427952
ER

PT J
AU Djamshidian, A
   O'Sullivan, SS
   Lees, A
   Averbeck, BB
AF Djamshidian, Atbin
   O'Sullivan, Sean S.
   Lees, Andrew
   Averbeck, Bruno B.
TI Effects of Dopamine on Sensitivity to Social Bias in Parkinson's Disease
SO PLOS ONE
LA English
DT Article
ID FACIAL EXPRESSION RECOGNITION; ANTERIOR CINGULATE CORTEX; IMPAIRED
   RECOGNITION; PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS; DECISION-MAKING;
   ANGRY FACES; SCHIZOPHRENIA; BEHAVIORS; OXYTOCIN
AB Patients with Parkinson's disease (PD) sometimes develop impulsive compulsive behaviours (ICBs) due to their dopaminergic medication. We compared 26 impulsive and 27 non-impulsive patients with PD, both on and off medication, on a task that examined emotion bias in decision making. No group differences were detected, but patients on medication were less biased by emotions than patients off medication and the strongest effects were seen in patients with ICBs. PD patients with ICBs on medication also showed more learning from negative feedback and less from positive feedback, whereas off medication they showed the opposite effect.
C1 [Djamshidian, Atbin; O'Sullivan, Sean S.; Lees, Andrew] UCL, Dept Mol Neurosci, London, England.
   [Averbeck, Bruno B.] UCL, Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, London, England.
   [Djamshidian, Atbin; O'Sullivan, Sean S.; Lees, Andrew] UCL, Reta Lila Weston Inst Neurol Studies, London, England.
   [Averbeck, Bruno B.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
RP Djamshidian, A (reprint author), UCL, Dept Mol Neurosci, London, England.
EM bruno.averbeck@nih.gov
RI Lees, Andrew/A-6605-2009; O'Sullivan, Sean/C-9333-2012; 
OI O'Sullivan, Sean/0000-0002-0583-7956; Djamshidian,
   Atbin/0000-0001-7174-6000
FU Reta Lila Howard Foundation; NIH; Wellcome Trust; PSP Association;
   Weston Trust
FX This study was funded by the Reta Lila Howard Foundation, the Intramural
   research program of the NIH and the Wellcome Trust. The funders had no
   role in study design, data collection and analysis, decision to publish,
   or preparation of the manuscript.; SOS has received honoraria from
   Britannia Pharmaceuticals, AJL has received honoraria from Novartis,
   Teva, Meda, Boehringer Ingelheim, GSK, Ipsen, Lundbeck, Allergan, Orion;
   Grants: PSP Association, and the Weston Trust. There are no patents,
   products in development or marketed products to declare. This does not
   alter the authors' adherence to all the PLoS ONE policies on sharing
   data and materials, as detailed online in the guide for authors.
NR 43
TC 2
Z9 2
U1 0
U2 8
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 MAR 9
PY 2012
VL 7
IS 3
AR e32889
DI 10.1371/journal.pone.0032889
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 929KX
UT WOS:000303062800034
PM 22427905
ER

PT J
AU Gallo, A
   Tandon, M
   Alevizos, I
   Illei, GG
AF Gallo, Alessia
   Tandon, Mayank
   Alevizos, Ilias
   Illei, Gabor G.
TI The Majority of MicroRNAs Detectable in Serum and Saliva Is Concentrated
   in Exosomes
SO PLOS ONE
LA English
DT Article
ID CIRCULATING MICRORNAS; BIOMARKERS; MICROVESICLES; VESICLES; RELEASE;
   PLASMA; ROLES; CELL
AB There is an increasing interest in using microRNAs (miRNA) as biomarkers in autoimmune diseases. They are easily accessible in many body fluids but it is controversial if they are circulating freely or are encapsulated in microvesicles, particularly exosomes. We investigated if the majority of miRNas in serum and saliva are free-circulating or concentrated in exosomes. Exosomes were isolated by ultracentrifugation from fresh and frozen human serum and saliva. The amount of selected miRNAs extracted from the exosomal pellet and the exosome-depleted serum and saliva was compared by quantitative RT-PCR. Some miRNAs tested are ubiquitously expressed, others were previously reported as biomarkers. We included miRNAs previously reported to be free circulating and some thought to be exosome specific. The purity of exosome fraction was confirmed by electronmicroscopy and western blot. The concentration of miRNAs was consistently higher in the exosome pellet compared to the exosome-depleted supernatant. We obtained the same results using an equal volume or equal amount of total RNA as input of the RT-qPCR. The concentration of miRNA in whole, unfractionated serum, was between the exosomal pellet and the exosome-depleted supernatant. Selected miRNAs, which were detectable in exosomes, were undetectable in whole serum and the exosome-depleted supernantant. Exosome isolation improves the sensitivity of miRNA amplification from human biologic fluids. Exosomal miRNA should be the starting point for early biomarker studies to reduce the probability of false negative results involving low abundance miRNAs that may be missed by using unfractionated serum or saliva.
C1 [Gallo, Alessia; Tandon, Mayank; Alevizos, Ilias; Illei, Gabor G.] Natl Inst Dent & Craniofacial Res, Sjogrens Syndrome Clin, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA.
RP Gallo, A (reprint author), Natl Inst Dent & Craniofacial Res, Sjogrens Syndrome Clin, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA.
EM illeig@mail.nih.gov
FU National Institute of Dental and Craniofacial Research
FX This research was supported by the Intramural Research Program of the
   National Institute of Dental and Craniofacial Research. The funders had
   no role in study design, data collection and analysis, decision to
   publish, or preparation of the manuscript.
NR 14
TC 272
Z9 294
U1 10
U2 74
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 MAR 9
PY 2012
VL 7
IS 3
AR e30679
DI 10.1371/journal.pone.0030679
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 929KX
UT WOS:000303062800002
PM 22427800
ER

PT J
AU Nayak, B
   Dias, FM
   Kumar, S
   Paldurai, A
   Collins, PL
   Samal, SK
AF Nayak, Baibaswata
   Dias, Flavia Militino
   Kumar, Sachin
   Paldurai, Anandan
   Collins, Peter L.
   Samal, Siba K.
TI Avian paramyxovirus serotypes 2-9 (APMV-2-9) vary in the ability to
   induce protective immunity in chickens against challenge with virulent
   Newcastle disease virus (APMV-1)
SO VACCINE
LA English
DT Article
DE Newcastle disease; NDV; Avian paramyxovirus; APMV; Vaccine; NDV
   challenge; Survival
ID COMPLETE GENOME SEQUENCE; TURKEYS; STRAIN; RESISTANCE; YUCAIPA;
   NEURAMINIDASE; INFLUENZA; INFECTION; PROTEINS; POULTRY
AB The avian paramyxoviruses (APMVs) belong to the genus Avulavirus of family Paramyxoviridae. The APMVs are classified into nine serotypes on the basis of hemagglutination inhibition (HI) and neuraminidase inhibition (NI) assays, although some serologic cross-reaction exists. Newcastle disease virus (NDV), which constitutes serotype 1 (APMV-1), is an important pathogen of poultry, but the pathogenic potential of the other APMV serotypes is poorly understood. Although antibodies to APMV -2 to -9 are prevalent in chickens, the effect of prior exposure to these serotypes on susceptibility to NDV infection and disease was not known. In the present study, chickens were immunized with APMV-2 to -9 by the oculo-nasal route and later were challenged by the same route with a highly virulent strain of NDV. Among APMV-2 to -9, only APMV-3 induced serum antibodies that cross-reacted significantly with NDV and had significant NDV-neutralizing activity in vitro. In mock-immunized chickens, challenge NDV replicated throughout the respiratory tract as well as in the brain, spleen, and enteric tract. In contrast, in APMV-3-immunized chickens, challenge NDV replication was restricted to the upper respiratory tract and trachea. Some of the other APMVs also induced partial restriction of challenge NDV replication: for example, challenge NOV was not detected in the brains of APMV-9-immunized chickens, and shedding from the respiratory tract was reduced in chickens immunized with APMV-8 and -9. All of the chickens immunized with APMV-3 survived the NDV challenge; with APMV-2, -7, -8, and -9 the percentage survival was 30%, 20%, 20%, and 52.5%, respectively; whereas none of the chickens immunized with APMV-4, -5, or -6 survived. These results show that prior infection of chickens with APMV-3 induced substantial protection against NDV challenge, whereas prior infection with APMV-2, -7, -8, and -9 can alter subsequent NOV infection. The induction of NDV-neutralizing antibodies was a marker for efficient protection, but partial protection also was observed in their absence. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Nayak, Baibaswata; Dias, Flavia Militino; Kumar, Sachin; Paldurai, Anandan; Samal, Siba K.] Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
   [Collins, Peter L.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Samal, SK (reprint author), Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
EM ssamal@umd.edu
RI Nayak, Baibaswata/L-6156-2016
FU NIAID [N01A060009]; NIAID-NIH
FX We thank Daniel Rockemann for his excellent technical assistance and
   Lashae Green for proofreading the manuscript. "This research was
   supported by funding from NIAID contract no. N01A060009 (85% support)
   and NIAID-NIH Intramural Research Program (15% support). The views
   expressed herein do not necessarily reflect the official policies of the
   Department of Health and Human Services; nor does the mention of trade
   names, commercial practices, or organizations imply endorsement by the
   U.S. Government."
NR 35
TC 11
Z9 14
U1 0
U2 3
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 MAR 9
PY 2012
VL 30
IS 12
BP 2220
EP 2227
DI 10.1016/j.vaccine.2011.12.090
PG 8
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 924AN
UT WOS:000302662900032
PM 22222870
ER

PT J
AU Muenke, M
AF Muenke, Maximilian
TI 2011 William Allan Award Introduction: John M. Opitz
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Editorial Material
ID MULTIPLE CONGENITAL ANOMALIES; DEVELOPMENTAL FIELD CONCEPT; MUTATIONS
C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Muenke, M (reprint author), NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
EM mamuenke@mail.nih.gov
NR 15
TC 0
Z9 0
U1 0
U2 0
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 MAR 9
PY 2012
VL 90
IS 3
BP 390
EP 391
DI 10.1016/j.ajhg.2012.01.011
PG 2
WC Genetics & Heredity
SC Genetics & Heredity
GA 911ZI
UT WOS:000301762800003
PM 22405083
ER

PT J
AU Saxena, R
   Elbers, CC
   Guo, YR
   Peter, I
   Gaunt, TR
   Mega, JL
   Lanktree, MB
   Tare, A
   Castillo, BA
   Li, YR
   Johnson, T
   Bruinenberg, M
   Gilbert-Diamond, D
   Rajagopalan, R
   Voight, BF
   Balasubramanyam, A
   Barnard, J
   Bauer, F
   Baumert, J
   Bhangale, T
   Bohm, BO
   Braund, PS
   Burton, PR
   Chandrupatla, HR
   Clarke, R
   Cooper-DeHoff, RM
   Crook, ED
   Davey-Smith, G
   Day, IN
   de Boer, A
   de Groot, MCH
   Drenos, F
   Ferguson, J
   Fox, CS
   Furlong, CE
   Gibson, Q
   Gieger, C
   Gilhuijs-Pederson, LA
   Glessner, JT
   Goel, A
   Gong, Y
   Grant, SFA
   Grobbee, DE
   Hastie, C
   Humphries, SE
   Kim, CE
   Kivimaki, M
   Kleber, M
   Meisinger, C
   Kumari, M
   Langaee, TY
   Lawlor, DA
   Li, MY
   Lobmeyer, MT
   Maitland-van der Zee, AH
   Meijs, MFL
   Molony, CM
   Morrow, DA
   Murugesan, G
   Musani, SK
   Nelson, CP
   Newhouse, SJ
   O'Connell, JR
   Padmanabhan, S
   Palmen, J
   Patel, SR
   Pepine, CJ
   Pettinger, M
   Price, TS
   Rafelt, S
   Ranchalis, J
   Rasheed, A
   Rosenthal, E
   Ruczinski, I
   Shah, S
   Shen, HQ
   Silbernagel, G
   Smith, EN
   Spijkerman, AWM
   Stanton, A
   Steffes, MW
   Thorand, B
   Trip, M
   van der Harst, P
   van der A, DL
   van Iperen, EPA
   van Setten, J
   van Vliet-Ostaptchouk, JV
   Verweij, N
   Wolffenbuttel, BHR
   Young, T
   Zafarmand, MH
   Zmuda, JM
   Boehnke, M
   Altshuler, D
   McCarthy, M
   Kao, WHL
   Pankow, JS
   Cappola, TP
   Sever, P
   Poulter, N
   Caulfield, M
   Dominiczak, A
   Shields, DC
   Bhatt, DL
   Zhang, L
   Curtis, SP
   Danesh, J
   Casas, JP
   van der Schouw, YT
   Onland-Moret, NC
   Doevendans, PA
   Dorn, GW
   Farrall, M
   FitzGerald, GA
   Hamsten, A
   Hegele, R
   Hingorani, AD
   Hofker, MH
   Huggins, GS
   Illig, T
   Jarvik, GP
   Johnson, JA
   Klungel, OH
   Knowler, WC
   Koenig, W
   Marz, W
   Meigs, JB
   Melander, O
   Munroe, PB
   Mitchell, BD
   Bielinski, SJ
   Rader, DJ
   Reilly, MP
   Rich, SS
   Rotter, JI
   Saleheen, D
   Samani, NJ
   Schadt, EE
   Shuldiner, AR
   Silverstein, R
   Kottke-Marchant, K
   Talmud, PJ
   Watkins, H
   Asselbergs, FW
   de Bakker, PIW
   McCaffery, J
   Wijmenga, C
   Sabatine, MS
   Wilson, JG
   Reiner, A
   Bowden, DW
   Hakonarson, H
   Siscovick, DS
   Keating, BJ
AF Saxena, Richa
   Elbers, Clara C.
   Guo, Yiran
   Peter, Inga
   Gaunt, Tom R.
   Mega, Jessica L.
   Lanktree, Matthew B.
   Tare, Archana
   Almoguera Castillo, Berta
   Li, Yun R.
   Johnson, Toby
   Bruinenberg, Marcel
   Gilbert-Diamond, Diane
   Rajagopalan, Ramakrishnan
   Voight, Benjamin F.
   Balasubramanyam, Ashok
   Barnard, John
   Bauer, Florianne
   Baumert, Jens
   Bhangale, Tushar
   Boehm, Bernhard O.
   Braund, Peter S.
   Burton, Paul R.
   Chandrupatla, Hareesh R.
   Clarke, Robert
   Cooper-DeHoff, Rhonda M.
   Crook, Errol D.
   Davey-Smith, George
   Day, Ian N.
   de Boer, Anthonius
   de Groot, Mark C. H.
   Drenos, Fotios
   Ferguson, Jane
   Fox, Caroline S.
   Furlong, Clement E.
   Gibson, Quince
   Gieger, Christian
   Gilhuijs-Pederson, Lisa A.
   Glessner, Joseph T.
   Goel, Anuj
   Gong, Yan
   Grant, Struan F. A.
   Grobbee, Diederick E.
   Hastie, Claire
   Humphries, Steve E.
   Kim, Cecilia E.
   Kivimaki, Mika
   Kleber, Marcus
   Meisinger, Christa
   Kumari, Meena
   Langaee, Taimour Y.
   Lawlor, Debbie A.
   Li, Mingyao
   Lobmeyer, Maximilian T.
   Maitland-van der Zee, Anke-Hilse
   Meijs, Matthijs F. L.
   Molony, Cliona M.
   Morrow, David A.
   Murugesan, Gurunathan
   Musani, Solomon K.
   Nelson, Christopher P.
   Newhouse, Stephen J.
   O'Connell, Jeffery R.
   Padmanabhan, Sandosh
   Palmen, Jutta
   Patel, Sanjey R.
   Pepine, Carl J.
   Pettinger, Mary
   Price, Thomas S.
   Rafelt, Suzanne
   Ranchalis, Jane
   Rasheed, Asif
   Rosenthal, Elisabeth
   Ruczinski, Ingo
   Shah, Sonia
   Shen, Haiqing
   Silbernagel, Guenther
   Smith, Erin N.
   Spijkerman, Annemieke W. M.
   Stanton, Alice
   Steffes, Michael W.
   Thorand, Barbara
   Trip, Mieke
   van der Harst, Pim
   van der A, Daphne L.
   van Iperen, Erik P. A.
   van Setten, Jessica
   van Vliet-Ostaptchouk, Jana V.
   Verweij, Niek
   Wolffenbuttel, Bruce H. R.
   Young, Taylor
   Zafarmand, M. Hadi
   Zmuda, Joseph M.
   Boehnke, Michael
   Altshuler, David
   McCarthy, Mark
   Kao, W. H. Linda
   Pankow, James S.
   Cappola, Thomas P.
   Sever, Peter
   Poulter, Neil
   Caulfield, Mark
   Dominiczak, Anna
   Shields, Denis C.
   Bhatt, Deepak L.
   Zhang, Li
   Curtis, Sean P.
   Danesh, John
   Casas, Juan P.
   van der Schouw, Yvonne T.
   Onland-Moret, N. Charlotte
   Doevendans, Pieter A.
   Dorn, Gerald W., II
   Farrall, Martin
   FitzGerald, Garret A.
   Hamsten, Anders
   Hegele, Robert
   Hingorani, Aroon D.
   Hofker, Marten H.
   Huggins, Gordon S.
   Illig, Thomas
   Jarvik, Gail P.
   Johnson, Julie A.
   Klungel, Olaf H.
   Knowler, William C.
   Koenig, Wolfgang
   Maerz, Winfried
   Meigs, James B.
   Melander, Olle
   Munroe, Patricia B.
   Mitchell, Braxton D.
   Bielinski, Susan J.
   Rader, Daniel J.
   Reilly, Muredach P.
   Rich, Stephen S.
   Rotter, Jerome I.
   Saleheen, Danish
   Samani, Nilesh J.
   Schadt, Eric E.
   Shuldiner, Alan R.
   Silverstein, Roy
   Kottke-Marchant, Kandice
   Talmud, Philippa J.
   Watkins, Hugh
   Asselbergs, Folkert W.
   de Bakker, Paul I. W.
   McCaffery, Jeanne
   Wijmenga, Cisca
   Sabatine, Marc S.
   Wilson, James G.
   Reiner, Alex
   Bowden, Donald W.
   Hakonarson, Hakon
   Siscovick, David S.
   Keating, Brendan J.
CA Look AHEAD Res Grp
   Diagram Consortium
   ASCOT Investigators
   PROCARDIS
TI Large-Scale Gene-Centric Meta-Analysis across 39 Studies Identifies Type
   2 Diabetes Loci
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; INSULIN-RESISTANCE; COMMON
   VARIANTS; EUROPEAN AMERICANS; AFRICAN-AMERICANS; BLOOD-PRESSURE;
   RESOURCE CARE; RISK-FACTORS; SNP ARRAY
AB To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom similar to 50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with similar to 2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and clinical trials totaling 17,418 cases and 70,298 controls. First, meta-analysis of 25 studies comprising 14,073 cases and 57,489 controls of European descent confirmed eight established T2D loci at genome-wide significance. In silico follow-up analysis of putative association signals found in independent genome-wide association studies (including 8,130 cases and 38,987 controls) performed by the DIAGRAM consortium identified a T2D locus at genome-wide significance (GATAD2A/CILP2/PBX4; p = 5.7 x 10(-9)) and two loci exceeding study-wide significance (SREBF1, and TH/INS; p < 2.4 x 10(-6)). Second, meta-analyses of 1,986 cases and 7,695 controls from eight African-American studies identified study-wide-significant (p = 2.4 x 10(-7)) variants in HMGA2 and replicated variants in TCF7L2 (p = 5.1 x 10(-15)). Third, conditional analysis revealed multiple known and novel independent signals within five T2D-associated genes in samples of European ancestry and within HMGA2 in African-American samples. Fourth, a multiethnic meta-analysis of all 39 studies identified T2D-associated variants in BCL2 (p = 2.1 x 10(-8)). Finally, a composite genetic score of SNPs from new and established T2D signals was significantly associated with increased risk of diabetes in African-American, Hispanic, and Asian populations. In summary, large-scale meta-analysis involving a dense gene-centric approach has uncovered additional loci and variants that contribute to T2D risk and suggests substantial overlap of T2D association signals across multiple ethnic groups.
C1 [Saxena, Richa; Tare, Archana; Voight, Benjamin F.; Altshuler, David] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
   [Saxena, Richa; Tare, Archana; Voight, Benjamin F.; Young, Taylor; Altshuler, David; de Bakker, Paul I. W.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
   [Saxena, Richa] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
   [Elbers, Clara C.] Univ Penn, Dept Genet, Sch Med, Philadelphia, PA 19104 USA.
   [Elbers, Clara C.; Bauer, Florianne; Onland-Moret, N. Charlotte; de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Complex Genet Sect, Dept Med Genet, Utrecht, Netherlands.
   [Elbers, Clara C.; Bauer, Florianne; Grobbee, Diederick E.; van der Schouw, Yvonne T.; Onland-Moret, N. Charlotte; Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
   [Guo, Yiran; Almoguera Castillo, Berta; Li, Yun R.; Glessner, Joseph T.; Grant, Struan F. A.; Kim, Cecilia E.; Hakonarson, Hakon; Keating, Brendan J.] Childrens Hosp, Ctr Appl Genom, Abramson Res Ctr, Philadelphia, PA 19104 USA.
   [Guo, Yiran] BGI Shenzhen, Shenzhen 518083, Peoples R China.
   [Peter, Inga] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA.
   [Gaunt, Tom R.; Davey-Smith, George; Day, Ian N.; Lawlor, Debbie A.] Univ Bristol, Med Res Council Ctr Causal Anal Translat Epidemio, Dept Social Med, Bristol BS8 2BN, Avon, England.
   [Mega, Jessica L.; Morrow, David A.; Sabatine, Marc S.] Brigham & Womens Hosp, Div Cardiovasc, Thrombolysis Myocardial Infarct Study Grp, Boston, MA 02115 USA.
   [Lanktree, Matthew B.; Hegele, Robert] Univ Western Ontario, Dept Biochem, London, ON N6A 5C1, Canada.
   [Almoguera Castillo, Berta] Fdn Jimenez Diaz, Serv Genet, Inst Invest Sanitaria, Madrid 228040, Spain.
   [Johnson, Toby; Newhouse, Stephen J.; Caulfield, Mark; Munroe, Patricia B.] Queen Mary Univ London, Barts & London Genome Ctr, London EC1M 6BQ, England.
   [Johnson, Toby; Newhouse, Stephen J.; Caulfield, Mark; Munroe, Patricia B.] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med, London EC1M 6BQ, England.
   [Bruinenberg, Marcel] Univ Groningen, LifeLines Cohort Study & Biobank, Univ Med Ctr Groningen, NL-9700 AB Groningen, Netherlands.
   [Gilbert-Diamond, Diane] Childrens Environm Hlth & Dis Prevent Ctr Dartmou, Hanover, NH 03755 USA.
   [Gilbert-Diamond, Diane] Dartmouth Med Sch, Sect Biostat & Epidemiol, Dept Community & Family Med, Hanover, NH 03756 USA.
   [Rajagopalan, Ramakrishnan; Furlong, Clement E.; Ranchalis, Jane; Rosenthal, Elisabeth; Jarvik, Gail P.] Univ Washington, Dept Med Med Genet, Seattle, WA 98195 USA.
   [Balasubramanyam, Ashok] Baylor Coll Med, Translat Metab Unit, Div Diabet Endocrinol & Metab, Houston, TX 77030 USA.
   [Barnard, John; Zhang, Li] Cleveland Clin, Dept Quantitat Hlth Sci, Lerner Res Inst, Cleveland, OH 44195 USA.
   [Baumert, Jens; Meisinger, Christa; Thorand, Barbara] German Res Ctr Environm Hlth, Inst Epidemiol 2, Helmholtz Zentrum Munchen, Neuherberg, Germany.
   [Bhangale, Tushar; Furlong, Clement E.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
   [Boehm, Bernhard O.] Cardiol Grp Frankfurt Sachsenhausen, D-60598 Frankfurt, Germany.
   [Braund, Peter S.; Nelson, Christopher P.; Rafelt, Suzanne; Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Glenfield Hosp, Leicester LE3 9QP, Leics, England.
   [Burton, Paul R.] Univ Leicester, Dept Hlth Sci, Leicester LE1 7RH, Leics, England.
   [Chandrupatla, Hareesh R.; Ferguson, Jane; Li, Mingyao; Cappola, Thomas P.; Rader, Daniel J.; Reilly, Muredach P.] Univ Penn, Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA.
   [Clarke, Robert] Clin Trial Serv Unit, Oxford OX3 7LF, England.
   [Cooper-DeHoff, Rhonda M.; Langaee, Taimour Y.; Johnson, Julie A.] Univ Florida, Dept Pharmacotherapy & Translat Res, Coll Pharm, Gainesville, FL 32610 USA.
   [Cooper-DeHoff, Rhonda M.; Gong, Yan; Lobmeyer, Maximilian T.; Pepine, Carl J.; Johnson, Julie A.] Univ Florida, Coll Med, Div Cardiovasc Med, Gainesville, FL 32610 USA.
   [Crook, Errol D.] Univ S Alabama, Mobile, AL 36608 USA.
   [de Boer, Anthonius; de Groot, Mark C. H.; Gilhuijs-Pederson, Lisa A.; Maitland-van der Zee, Anke-Hilse; Klungel, Olaf H.] Univ Utrecht, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht Inst Pharmaceut Sci, Fac Sci, Utrecht, Netherlands.
   [Drenos, Fotios; Humphries, Steve E.; Palmen, Jutta; Talmud, Philippa J.] UCL, Ctr Cardiovasc Genet, Dept Med, London WC1E 6JF, England.
   [Fox, Caroline S.] Boston Univ, Sch Med, Boston, MA 02118 USA.
   [Gibson, Quince; O'Connell, Jeffery R.; Shen, Haiqing; Mitchell, Braxton D.; Shuldiner, Alan R.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
   [Gieger, Christian; Illig, Thomas] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.
   [Goel, Anuj; McCarthy, Mark; Farrall, Martin] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Hastie, Claire; Padmanabhan, Sandosh; Dominiczak, Anna] Univ Glasgow, British Heart Fdn Glasgow, Cardiovasc Res Ctr, Div Cardiovasc & Med Sci,Western Infirm, Glasgow G12 8TA, Lanark, Scotland.
   [Kivimaki, Mika; Casas, Juan P.] UCL, Dept Epidemiol & Publ Hlth, London, England.
   [Kivimaki, Mika; Kumari, Meena] UCL, Genet Epidemiol Grp, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England.
   [Kleber, Marcus] LURIC Study, D-79098 Freiburg, Germany.
   [Kleber, Marcus; Maerz, Winfried] Synlab Ctr Lab Diagnost Heidelberg, D-69037 Heidelberg, Germany.
   [Meijs, Matthijs F. L.; Zafarmand, M. Hadi; Doevendans, Pieter A.; Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands.
   [Molony, Cliona M.] Rosetta Inpharmat, Dept Genet, Seattle, WA 98109 USA.
   [Murugesan, Gurunathan] Cleveland Clin, Dept Clin Pathol, Pathol & Lab Med Inst, Cleveland, OH 44106 USA.
   [Musani, Solomon K.; Wilson, James G.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
   [Patel, Sanjey R.] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA.
   [Pettinger, Mary; Reiner, Alex] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
   [Price, Thomas S.] Kings Coll London, Med Res Council, Social Genet & Dev Psychiat Ctr, Inst Psychiat, London WC2R 2LS, England.
   [Rasheed, Asif; Saleheen, Danish] Ctr Noncommunicable Dis, Karachi, Pakistan.
   [Ruczinski, Ingo] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
   [Shah, Sonia] UCL, Univ Coll Genet Inst, London WC1E 6BT, England.
   [Silbernagel, Guenther] Univ Tubingen, Div Endocrinol Diabetol Nephrol Vasc Dis & Clin C, Dept Internal Med, D-72074 Tubingen, Germany.
   [Smith, Erin N.] Scripps Genom Med, La Jolla, CA 92037 USA.
   [Spijkerman, Annemieke W. M.; van der A, Daphne L.] Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands.
   [Stanton, Alice] Royal Coll Surgeons Ireland, Dublin 2, Ireland.
   [Steffes, Michael W.] Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
   [Trip, Mieke] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands.
   [van der Harst, Pim; Verweij, Niek] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9700 RB Groningen, Netherlands.
   [van der Harst, Pim; Wijmenga, Cisca] Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands.
   [van Iperen, Erik P. A.] Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands.
   [van Setten, Jessica; Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands.
   [van Vliet-Ostaptchouk, Jana V.] Univ Med Ctr Groningen, Dept Pathol & Med Biol, NL-9713 AV Groningen, Netherlands.
   [van Vliet-Ostaptchouk, Jana V.] Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, Groningen, Netherlands.
   [Wolffenbuttel, Bruce H. R.] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Groningen, Netherlands.
   [Zmuda, Joseph M.] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA.
   [Boehnke, Michael] Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Dept Biostat, Ann Arbor, MI 48109 USA.
   [Altshuler, David; Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
   [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [McCarthy, Mark] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England.
   [Kao, W. H. Linda] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD 21287 USA.
   [Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Sch Publ Hlth, Minneapolis, MN 55454 USA.
   [Sever, Peter; Poulter, Neil] Univ London Imperial Coll Sci Technol & Med, Int Ctr Circulatory Hlth, London W2 1PG, England.
   [Shields, Denis C.] Univ Coll Dublin, Conway Inst Biomol & Biomed Res, Dublin 4, Ireland.
   [Bhatt, Deepak L.] Harvard Univ, Sch Med, Cambridge, MA 02115 USA.
   [Curtis, Sean P.; Saleheen, Danish] Merck Res Labs, Rahway, NJ 07065 USA.
   [Danesh, John] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England.
   [Casas, Juan P.] London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, Fac Epidemiol & Populat Hlth, London WC1E 7HT, England.
   [Dorn, Gerald W., II; Watkins, Hugh] Washington Univ, Ctr Pharmacogenet, St Louis, MO 63110 USA.
   [Farrall, Martin] Univ Oxford, Dept Cardiovasc Med, John Radcliffe Hosp, Oxford OX3 9DU, England.
   [FitzGerald, Garret A.] Univ Penn, Inst Translat Med & Therapeut, Sch Med, Philadelphia, PA 19146 USA.
   [Hamsten, Anders] Karolinska Inst, Cardiovasc Genet Grp, Atherosclerosis Res Unit, Dept Med Solna, SE-17176 Stockholm, Sweden.
   [Hingorani, Aroon D.] UCL, Ctr Clin Pharmacol, Dept Med, London WC1E 6JF, England.
   [Huggins, Gordon S.] Tufts Med Ctr, Ctr Translat Genom, Mol Cardiol Res Inst, Boston, MA 02114 USA.
   [Huggins, Gordon S.] Tufts Univ, Boston, MA 02114 USA.
   [Illig, Thomas] Hannover Med Sch, Hannover Unified Biobank, D-30625 Hannover, Germany.
   [Knowler, William C.] NIDDK, Phoenix, AZ 85104 USA.
   [Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, Ulm, Germany.
   [Maerz, Winfried] Heidelberg Univ, Mannheim Inst Publ Hlth Social & Prevent Med, Med Fac Mannheim, D-68167 Mannheim, Germany.
   [Maerz, Winfried] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, A-8010 Graz, Austria.
   [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
   [Melander, Olle] Malmo Univ Hosp, Clin Res Ctr, SE-20502 Malmo, Sweden.
   [Bielinski, Susan J.] Mayo Clin, Coll Med, Div Epidemiol, Rochester, MN 55905 USA.
   [Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22902 USA.
   [Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
   [Schadt, Eric E.] Sage Bionetworks, Seattle, WA 98109 USA.
   [Silverstein, Roy] Case Western Reserve Univ, Dept Cell Biol, Lerner Res Inst,Dept Mol Med, Cleveland Clin Fdn,Cleveland Clin Lerner Coll Med, Cleveland, OH 44195 USA.
   [Kottke-Marchant, Kandice] Cleveland Clin, Pathol & Lab Med Inst, Cleveland, OH 44195 USA.
   [de Bakker, Paul I. W.] Harvard Univ, Sch Med, Div Genet, Brigham & Womens Hosp, Boston, MA 02115 USA.
   [McCaffery, Jeanne] Brown Univ, Miriam Hosp, Weight Control & Diabet Res Ctr, Providence, RI 02906 USA.
   [McCaffery, Jeanne] Brown Univ, Warren Alpert Sch Med, Providence, RI 02906 USA.
   [Bowden, Donald W.] Wake Forest Univ, Bowman Gray Sch Med, Ctr Human Genom, Winston Salem, NC 27106 USA.
   [Hakonarson, Hakon; Keating, Brendan J.] Childrens Hosp, Div Human Genet, Abramson Res Ctr, Philadelphia, PA 19104 USA.
   [Hakonarson, Hakon; Keating, Brendan J.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA.
   [Siscovick, David S.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98101 USA.
   [Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA.
RP Saxena, R (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
EM rsaxena@chgr.mgh.harvard.edu; keatingb@email.chop.edu
RI Davey Smith, George/A-7407-2013; Price, Thomas/B-7372-2008; Thorand,
   Barbara/B-5349-2014; Jarvik, Gail/N-6476-2014; Gaunt, Tom/O-3918-2014;
   Onland-Moret, N. Charlotte/G-9185-2011; de Groot, Mark/A-9891-2012;
   Hegele, Robert/G-3301-2011; Bielinski, Suzette/A-2238-2009; Burton,
   Paul/H-7527-2016; Klungel, Olaf/I-9563-2016; Padmanabhan,
   Sandosh/S-3963-2016; Verweij, Niek/A-4499-2017; Guo, Yiran/H-4120-2011;
   Smith, Erin/E-5933-2011; Newhouse, Stephen/C-9330-2011; Ferguson,
   Jane/C-7154-2011; Wolffenbuttel, Bruce/A-8419-2011; Stanton,
   Alice/F-4697-2012; Grobbee, Diederick/C-7651-2014; Wijmenga,
   Cisca/D-2173-2009; Altshuler, David/A-4476-2009; de Bakker,
   Paul/B-8730-2009; Shah, Sonia/N-7547-2013; Meisinger,
   Christine/B-5358-2014
OI Lawlor, Debbie A/0000-0002-6793-2262; Pankow, James/0000-0001-7076-483X;
   Kleber, Marcus/0000-0003-0663-7275; Gieger,
   Christian/0000-0001-6986-9554; Wijmenga, Cisca/0000-0002-5635-1614;
   Patel, Sanjay/0000-0002-9142-5172; Kumari, Meena/0000-0001-9716-1035;
   Verweij, Niek/0000-0002-4303-7685; Meisinger,
   Christa/0000-0002-9026-6544; Watkins, Hugh/0000-0002-5287-9016; van
   Iperen, Erik/0000-0001-7107-3168; Mitchell, Braxton/0000-0003-4920-4744;
   Davey Smith, George/0000-0002-1407-8314; Lanktree,
   Matthew/0000-0002-5750-6286; Stanton, Alice/0000-0002-4961-165X; van
   Vliet-Ostaptchouk, Jana/0000-0002-7943-3153; Kivimaki,
   Mika/0000-0002-4699-5627; Talmud, Philippa/0000-0002-5560-1933; Johnson,
   Toby/0000-0002-5998-3270; Padmanabhan, Sandosh/0000-0003-3869-5808;
   Humphries, Stephen E/0000-0002-8221-6547; Price,
   Thomas/0000-0001-7356-2109; Thorand, Barbara/0000-0002-8416-6440;
   Jarvik, Gail/0000-0002-6710-8708; Gaunt, Tom/0000-0003-0924-3247; de
   Groot, Mark/0000-0002-5764-5788; Bielinski, Suzette/0000-0002-2905-5430;
   Guo, Yiran/0000-0002-6549-8589; Newhouse, Stephen/0000-0002-1843-9842;
   Ferguson, Jane/0000-0001-6896-1025; Wolffenbuttel,
   Bruce/0000-0001-9262-6921; Grobbee, Diederick/0000-0003-4472-4468;
   Altshuler, David/0000-0002-7250-4107; de Bakker,
   Paul/0000-0001-7735-7858; Shah, Sonia/0000-0001-5860-4526; 
FU National Heart, Lung, and Blood Institute; NIDDK NIH [DK089378];
   Netherlands Organization for Scientific Research (NWO); Massachusetts
   Institute of Technology [N01-HC-65226]
FX The CARe Consortium wishes to acknowledge the support of the National
   Heart, Lung, and Blood Institute and the contributions of the research
   institutions, study investigators, field staff, and study participants
   in creating this resource for biomedical research. The following nine
   parent studies have contributed parent study data, ancillary study data,
   and DNA samples through the Broad Institute of Harvard University and
   the Massachusetts Institute of Technology (N01-HC-65226) to create this
   genotype/phenotype database for wide dissemination to the biomedical
   research community: the Atherosclerosis Risk in Communities (ARIC)
   study, the Cardiovascular Health Study (CHS), the Cleveland Family Study
   (CFS), the Cooperative Study of Sickle Cell Disease (CSSCD), the
   Coronary Artery Risk Development in Young Adults (CARDIA) study, the
   Framingham Heart Study (FHS), the Jackson Heart Study OHS), the
   Multi-Ethnic Study of Atherosclerosis (MESA), and the Sleep Heart Health
   Study (SHHS). R.S. is partially supported by NIDDK NIH R21 (DK089378).
   C.C.E is supported by a Rubicon grant from the Netherlands Organization
   for Scientific Research (NWO). Additional acknowledgements for each
   cohort are listed in the Supplemental Data. Also see the Supplemental
   Data for conflict-of-interest disclosures for some of the authors.
NR 80
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U1 1
U2 30
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 MAR 9
PY 2012
VL 90
IS 3
BP 410
EP 425
DI 10.1016/j.ajhg.2011.12.022
PG 16
WC Genetics & Heredity
SC Genetics & Heredity
GA 911ZI
UT WOS:000301762800007
PM 22325160
ER

PT J
AU Kummar, S
   Chen, A
   Parchment, RE
   Kinders, RJ
   Ji, J
   Tomaszewski, JE
   Doroshow, JH
AF Kummar, Shivaani
   Chen, Alice
   Parchment, Ralph E.
   Kinders, Robert J.
   Ji, Jay
   Tomaszewski, Joseph E.
   Doroshow, James H.
TI Advances in using PARP inhibitors to treat cancer
SO BMC MEDICINE
LA English
DT Review
DE synthetic lethality; DNA repair; PARP clinical trials
ID ADP-RIBOSE POLYMERASE; 0 CLINICAL-TRIAL; POLY(ADP-RIBOSE) POLYMERASE;
   SYNTHETIC LETHALITY; OVARIAN-CARCINOMA; BRCA2 MUTATIONS;
   EXCISION-REPAIR; BREAST-CANCER; MUTANT-CELLS; DNA
AB The poly (ADP-ribose) polymerase (PARP) family of enzymes plays a critical role in the maintenance of DNA integrity as part of the base excision pathway of DNA repair. PARP1 is overexpressed in a variety of cancers, and its expression has been associated with overall prognosis in cancer, especially breast cancer. A series of new therapeutic agents that are potent inhibitors of the PARP1 and PARP2 isoforms have demonstrated important clinical activity in patients with breast or ovarian cancers that are caused by mutations in either the BRCA1 or 2 genes. Results from such studies may define a new therapeutic paradigm, wherein simultaneous loss of the capacity to repair DNA damage may have antitumor activity in itself, as well as enhance the antineoplastic potential of cytotoxic chemotherapeutic agents.
C1 [Kummar, Shivaani; Chen, Alice; Tomaszewski, Joseph E.; Doroshow, James H.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
   [Parchment, Ralph E.; Kinders, Robert J.; Ji, Jay] NCI, Sci Applicat Int Corporat Frederick Inc, Appl Dev Res Directorate, Frederick, MD 21702 USA.
   [Doroshow, James H.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Doroshow, JH (reprint author), NCI, Div Canc Treatment & Diag, Bldg 31,Room 3A-44,31 Ctr Dr, Bethesda, MD 20892 USA.
EM doroshoj@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
   [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer
   Research; Division of Cancer Treatment and Diagnosis of the National
   Cancer Institute
FX This project has been funded in whole or in part with federal funds from
   the National Cancer Institute, National Institutes of Health, under
   Contract No. HHSN261200800001E. The content of this publication does not
   necessarily reflect the views or policies of the Department of Health
   and Human Services, nor does mention of trade names, commercial
   products, or organizations imply endorsement by the US Government. This
   research was supported in part by the Intramural Research Program of the
   NIH, National Cancer Institute, Center for Cancer Research and the
   Developmental Therapeutics Program in the Division of Cancer Treatment
   and Diagnosis of the National Cancer Institute.
NR 33
TC 68
Z9 74
U1 5
U2 35
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 MAR 9
PY 2012
VL 10
AR 25
DI 10.1186/1741-7015-10-25
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA 914JE
UT WOS:000301944900001
PM 22401667
ER

PT J
AU de Castro, RO
   Zhang, J
   Groves, JR
   Barbu, EA
   Siraganian, RP
AF de Castro, Rodrigo Orlandini
   Zhang, Juan
   Groves, Jacqueline R.
   Barbu, Emilia Alina
   Siraganian, Reuben P.
TI Once Phosphorylated, Tyrosines in Carboxyl Terminus of Protein-tyrosine
   Kinase Syk Interact with Signaling Proteins, Including TULA-2, a
   Negative Regulator of Mast Cell Degranulation
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID FC-EPSILON-RI; AFFINITY IGE RECEPTOR; ACTIVATION LOOP TYROSINES; ADAPTER
   PROTEINS; ACTIN CYTOSKELETON; PHOSPHATASE; SLP-76; SHIP; IDENTIFICATION;
   SPECIFICITY
AB Activation of the high affinity IgE-binding receptor (Fc epsilon RI) results in the tyrosine phosphorylation of two conserved tyrosines located close to the COOH terminus of the protein-tyrosine kinase Syk. Synthetic peptides representing the last 10 amino acids of the tail of Syk with these two tyrosines either nonphosphorylated or phosphorylated were used to precipitate proteins from mast cell lysates. Proteins specifically precipitated by the phosphorylated peptide were identified by mass spectrometry. These included the adaptor proteins SLP-76, Nck-1, Grb2, and Grb2-related adaptor downstream of Shc (GADS) and the protein phosphatases SHIP-1 and TULA-2 (also known as UBASH3B or STS-1). The presence of these in the precipitates was further confirmed by immunoblotting. Using the peptides as probes in far Western blots showed direct binding of the phosphorylated peptide to Nck-1 and SHIP-1. Immunoprecipitations suggested that there were complexes of these proteins associated with Syk especially after receptor activation; in these complexes are Nck, SHIP-1, SLP-76, Grb2, and TULA-2 (UBASH3B or STS-1). The decreased expression of TULA-2 by treatment of mast cells with siRNA increased the Fc epsilon RI-induced tyrosine phosphorylation of the activation loop tyrosines of Syk and the phosphorylation of phospholipase C-gamma 2. There was parallel enhancement of the receptor-induced degranulation and activation of nuclear factor for T cells or nuclear factor kappa B, indicating that TULA-2, like SHIP-1, functions as a negative regulator of Fc epsilon RI signaling in mast cells. Therefore, once phosphorylated, the terminal tyrosines of Syk bind complexes of proteins that are positive and negative regulators of signaling in mast cells.
C1 [de Castro, Rodrigo Orlandini; Zhang, Juan; Groves, Jacqueline R.; Barbu, Emilia Alina; Siraganian, Reuben P.] NIDCR, Receptors & Signal Transduct Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA.
RP Siraganian, RP (reprint author), NIDCR, Receptors & Signal Transduct Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA.
EM rs53x@nih.gov
FU National Institutes of Health, NIDCR
FX This work was supported, in whole or in part, by the National Institutes
   of Health National Institutes of Health Intramural Research Program,
   NIDCR.
NR 59
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Z9 12
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 MAR 9
PY 2012
VL 287
IS 11
BP 8194
EP 8204
DI 10.1074/jbc.M111.326850
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 906MN
UT WOS:000301349400035
PM 22267732
ER

PT J
AU Zhuang, M
   Wang, W
   De Feo, CJ
   Vassell, R
   Weiss, CD
AF Zhuang, Min
   Wang, Wei
   De Feo, Christopher J.
   Vassell, Russell
   Weiss, Carol D.
TI Trimeric, Coiled-coil Extension on Peptide Fusion Inhibitor of HIV-1
   Influences Selection of Resistance Pathways
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; TERMINAL HEPTAD REPEAT; ENVELOPE
   GLYCOPROTEIN; SIV GP41; TRANSMEMBRANE GLYCOPROTEIN; CROSS-RESISTANCE;
   ATOMIC-STRUCTURE; MEMBRANE-FUSION; ENTRY INHIBITOR; CORE STRUCTURE
AB Peptides corresponding to N- and C-terminal heptad repeat regions (HR1 and HR2, respectively) of viral fusion proteins can block infection of viruses in a dominant negative manner by interfering with refolding of the viral HR1 and HR2 to form a six-helix bundle (6HB) that drives fusion between viral and host cell membranes. The 6HB of the HIV gp41 (endogenous bundle) consists of an HR1 coiled-coil trimer with grooves lined by antiparallel HR2 helices. HR1 peptides form coiled-coil oligomers that may bind to gp41 HR2 as trimers to form a heterologous 6HB (inhibitor bundle) or to gp41 HR1 as monomers or dimers to form a heterologous coiled coil. To gain insights into mechanisms of Env entry and inhibition by HR1 peptides, we compared resistance to a peptide corresponding to 36 residues in gp41 HR1 (N36) and the same peptide with a coiled-coil trimerization domain fused to its N terminus (IZN36) that stabilizes the trimer and increases inhibitor potency (Eckert, D. M., and Kim, P. S. (2001) Proc. Nat. Acad. Sci. U. S. A. 98, 11187-11192). Whereas N36 selected two genetic pathways with equal probability, each defined by an early mutation in either HR1 or HR2, IZN36 preferentially selected the HR1 pathway. Both pathways conferred cross-resistance to both peptides. Each HR mutation enhanced the thermostability of the endogenous 6HB, potentially allowing the virus to simultaneously escape inhibitors targeting either gp41 HR1 or HR2. These findings inform inhibitor design and identify regions of plasticity in the highly conserved gp41 that modulate virus entry and escape from HR1 peptide inhibitors.
C1 [Weiss, Carol D.] NIH, Off Vaccine Res & Review, Ctr Biol Evaluat & Res, US FDA, Bethesda, MD 20892 USA.
   [Zhuang, Min] Harbin Med Univ, Dept Microbiol, Harbin 150086, Heilongjiang, Peoples R China.
RP Weiss, CD (reprint author), NIH, Off Vaccine Res & Review, Ctr Biol Evaluat & Res, US FDA, Bldg 29,Rm 532,29 Lincoln Dr, Bethesda, MD 20892 USA.
EM carol.weiss@fda.hhs.gov
RI Ghartouchent, malek/B-9088-2012; Weiss, Carol/F-6438-2011
OI Weiss, Carol/0000-0002-9965-1289
FU National Institutes of Health; United States Food and Drug
   Administration
FX This work was supported in part by the National Institutes of Health
   Intramural AIDS Targeted Antiviral Program (to C. D. W.). This work was
   also supported in part by institutional funds from the United States
   Food and Drug Administration.
NR 44
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U1 0
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAR 9
PY 2012
VL 287
IS 11
BP 8297
EP 8309
DI 10.1074/jbc.M111.324483
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 906MN
UT WOS:000301349400044
PM 22235115
ER

PT J
AU Deka, RK
   Brautigam, CA
   Goldberg, M
   Schuck, P
   Tomchick, DR
   Norgard, MV
AF Deka, Ranjit K.
   Brautigam, Chad A.
   Goldberg, Martin
   Schuck, Peter
   Tomchick, Diana R.
   Norgard, Michael V.
TI Structural, Bioinformatic, and In Vivo Analyses of Two Treponema
   pallidum Lipoproteins Reveal a Unique TRAP Transporter
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE TRAP transporter; syphilis; Treponema pallidum; TPR motif; protein
   interactions
ID EXTRACYTOPLASMIC-SOLUTE-RECEPTOR; SUBSTRATE-BINDING PROTEIN;
   CRYSTAL-STRUCTURE; HAEMOPHILUS-INFLUENZAE; ACID-BINDING;
   RHODOBACTER-CAPSULATUS; MALTOSE TRANSPORTER; MAXIMUM-LIKELIHOOD;
   OUTER-MEMBRANE; WATER CHANNEL
AB Treponema pallidum, the bacterial agent of syphilis, is predicted to encode one tripartite ATP-independent periplasmic transporter (TRAP-T). TRAP-Ts typically employ a periplasmic substrate-binding protein (SBP) to deliver the cognate ligand to the transmembrane symporter. Herein, we demonstrate that the genes encoding the putative TRAP-T components from T. pallidum, tp0957 (the SBP), and tp0958 (the symporter), are in an operon with an uncharacterized third gene, tp0956. We determined the crystal structure of recombinant Tp0956; the protein is trimeric and perforated by a pore. Part of Tp0956 forms an assembly similar to those of "tetratricopeptide repeat" (TPR) motifs. The crystal structure of recombinant Tp0957 was also determined; like the SBPs of other TRAP-Ts, there are two lobes separated by a cleft. In these other SBPs, the cleft binds a negatively charged ligand. However, the cleft of Tp0957 has a strikingly hydrophobic chemical composition, indicating that its ligand may be substantially different and likely hydrophobic. Analytical ultracentrifugation of the recombinant versions of Tp0956 and Tp0957 established that these proteins associate avidly. This unprecedented interaction was confirmed for the native molecules using in vivo cross-linking experiments. Finally, bioinforrnatic analyses suggested that this transporter exemplifies a new subfamily of TPATs (TPR-protein-associated TRAP-Ts) that require the action of a TPR-containing accessory protein for the periplasmic transport of a potentially hydrophobic ligand(s). (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Deka, Ranjit K.; Goldberg, Martin; Norgard, Michael V.] Univ Texas SW Med Ctr Dallas, Dept Microbiol, Dallas, TX 75390 USA.
   [Brautigam, Chad A.; Tomchick, Diana R.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
   [Schuck, Peter] Natl Inst Biomed Imaging & Bioengn, Dynam Mol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA.
RP Norgard, MV (reprint author), Univ Texas SW Med Ctr Dallas, Dept Microbiol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM Michael.Norgard@UTSouthwestern.edu
OI Schuck, Peter/0000-0002-8859-6966; Tomchick, Diana/0000-0002-7529-4643
FU National Institutes of Health [AI056305]; Welch Foundation [I-0940];
   National Institute of Biomedical Imaging and Bioengineering; U.S.
   Department of Energy, Office of Biological and Environmental Research
   [DE-AC02-06CH11357]
FX We thank Dr. Zhiming Ouyang for technical assistance with the RT-PCR
   analyses, the scientists in the University of Texas Southwestern Protein
   Chemistry Core for protein sequence and mass analyses, and Dr. Lisa
   Kinch for helpful comments on the bioinformatics. This research was
   supported by a National Institutes of Health grant (AI056305) and a
   Welch Foundation grant (I-0940) to M.V.N. This work was also supported
   in part by the Intramural Research Program of the National Institute of
   Biomedical Imaging and Bioengineering (P.S.). Results shown in this
   report are derived from work performed at Argonne National Laboratory,
   Structural Biology Center at the Advanced Photon Source. Argonne is
   operated by UChicago Argonne, LLC, for the U.S. Department of Energy,
   Office of Biological and Environmental Research, under contract
   DE-AC02-06CH11357.
NR 71
TC 12
Z9 12
U1 0
U2 6
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 MAR 9
PY 2012
VL 416
IS 5
BP 678
EP 696
DI 10.1016/j.jmb.2012.01.015
PG 19
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 910XV
UT WOS:000301682800007
PM 22306465
ER

PT J
AU Yuan, J
   Nguyen, CK
   Liu, XH
   Kanellopoulou, C
   Muljo, SA
AF Yuan, Joan
   Nguyen, Cuong K.
   Liu, Xiuhuai
   Kanellopoulou, Chrysi
   Muljo, Stefan A.
TI Lin28b Reprograms Adult Bone Marrow Hematopoietic Progenitors to Mediate
   Fetal-Like Lymphopoiesis
SO SCIENCE
LA English
DT Article
ID CD8(+) T-CELLS; STEM-CELLS; DEVELOPMENTAL SWITCH; MICRORNA BIOGENESIS;
   B-LYMPHOPOIESIS; NKT CELLS; EXPRESSION; LEVEL; MOUSE; MICE
AB The immune system develops in waves during ontogeny; it is initially populated by cells generated from fetal hematopoietic stem cells (HSCs) and later by cells derived from adult HSCs. Remarkably, the genetic programs that control these two distinct stem cell fates remain poorly understood. We report that Lin28b is specifically expressed in mouse and human fetal liver and thymus, but not in adult bone marrow or thymus. We demonstrate that ectopic expression of Lin28 reprograms hematopoietic stem/progenitor cells (HSPCs) from adult bone marrow, which endows them with the ability to mediate multilineage reconstitution that resembles fetal lymphopoiesis, including increased development of B-1a, marginal zone B, gamma/delta (gamma delta) T cells, and natural killer T (NKT) cells.
C1 [Yuan, Joan; Nguyen, Cuong K.; Liu, Xiuhuai; Kanellopoulou, Chrysi; Muljo, Stefan A.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Muljo, SA (reprint author), NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
EM stefan.muljo@nih.gov
RI yuan, joan/A-8185-2013; Muljo, Stefan/F-5671-2015; Nguyen,
   Cuong/D-7567-2013
OI yuan, joan/0000-0001-9129-8356; Muljo, Stefan/0000-0003-1013-446X;
   Nguyen, Cuong/0000-0002-1741-669X
FU NIAID, NIH
FX We thank W. E. Paul for his generous support and advice throughout; T.
   Bender, J. Daniel, B. J. Fowlkes, R. Germain, M. Lenardo, W. E. Paul,
   and M. Schlissel for critical reading of this manuscript and
   constructive suggestions; K. Laky and B. J. Fowlkes for valuable advice
   and antibodies; NIH Tetramer Core Facility for reagents; M. Holt for NKT
   cell discussions; P. Burr for sequencing; J. Edwards and C. Eigsti for
   cell sorting; M. Foster for animal care; R. Zahr for technical support;
   and N. Bartonicek (EMBL-EBI, Hinxton, UK) for providing the RefSeq 3'UTR
   library for Sylamer analysis. We gratefully acknowledge the
   high-performance computational capabilities of the Biowulf Linux cluster
   at the NIH (http://biowulf.nih.gov) and NIAID Office of Cyber
   Infrastructure and Computational Biology High-Performance Computing
   cluster required for massively parallel sequencing analyses. The data
   reported in this paper are tabulated in the main text and in the
   Supporting Online Material. The RNA-Seq and NanoString data are
   available in the Gene Expression Omnibus (GEO) database
   (www.ncbi.nlm.nih.gov/geo) under the accession nos. GSE34854, GSE35081,
   and GSE35107. The materials and reagents used in the paper are available
   under a Materials Transfer Agreement. We apologize that we could not
   cite all the relevant references because of space limitations. The
   Integrative Immunobiology Unit is supported by the Intramural Research
   Program of the NIAID, NIH. The authors declare no competing financial
   interests.
NR 52
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Z9 111
U1 1
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 MAR 9
PY 2012
VL 335
IS 6073
BP 1195
EP 1200
DI 10.1126/science.1216557
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 904VB
UT WOS:000301225100037
PM 22345399
ER

PT J
AU Mahat, DB
   Brennan-Laun, SE
   Fialcowitz-White, EJ
   Kishor, A
   Ross, CR
   Pozharskaya, T
   Rawn, JD
   Blackshear, PJ
   Hassel, BA
   Wilson, GM
AF Mahat, Dig B.
   Brennan-Laun, Sarah E.
   Fialcowitz-White, Elizabeth J.
   Kishor, Aparna
   Ross, Christina R.
   Pozharskaya, Tatyana
   Rawn, J. David
   Blackshear, Perry J.
   Hassel, Bret A.
   Wilson, Gerald M.
TI Coordinated Expression of Tristetraprolin Post-Transcriptionally
   Attenuates Mitogenic Induction of the Oncogenic Ser/Thr Kinase Pim-1
SO PLOS ONE
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; MESSENGER-RNA DECAY; NECROSIS-FACTOR-ALPHA;
   AU-RICH ELEMENTS; ZINC-FINGER PROTEINS; BINDING PROTEIN;
   POSTTRANSLATIONAL MODIFICATION; DEPENDENT PHOSPHORYLATION; ELAV PROTEIN;
   C-MYC
AB The serine/threonine kinase Pim-1 directs selected signaling events that promote cell growth and survival and is overexpressed in diverse human cancers. Pim-1 expression is tightly controlled through multiple mechanisms, including regulation of mRNA turnover. In several cultured cell models, mitogenic stimulation rapidly induced and stabilized PIM1 mRNA, however, vigorous destabilization 4-6 hours later helped restore basal expression levels. Acceleration of PIM1 mRNA turnover coincided with accumulation of tristetraprolin (TTP), an mRNA-destabilizing protein that targets transcripts containing AU-rich elements. TTP binds PIM1 mRNA in cells, and suppresses its expression by accelerating mRNA decay. Reporter mRNA decay assays localized the TTP-regulated mRNA decay element to a discrete AU-rich sequence in the distal 3'-untranslated region that binds TTP. These data suggest that coordinated stimulation of TTP and PIM1 expression limits the magnitude and duration of PIM1 mRNA accumulation by accelerating its degradation as TTP protein levels increase. Consistent with this model, PIM1 and TTP mRNA levels were well correlated across selected human tissue panels, and PIM1 mRNA was induced to significantly higher levels in mitogen-stimulated fibroblasts from TTP-deficient mice. Together, these data support a model whereby induction of TTP mediates a negative feedback circuit to limit expression of selected mitogen-activated genes.
C1 [Mahat, Dig B.; Brennan-Laun, Sarah E.; Fialcowitz-White, Elizabeth J.; Kishor, Aparna; Ross, Christina R.; Pozharskaya, Tatyana; Wilson, Gerald M.] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA.
   [Hassel, Bret A.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
   [Hassel, Bret A.; Wilson, Gerald M.] Univ Maryland, Sch Med, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
   [Rawn, J. David] Towson Univ, Dept Chem, Baltimore, MD 21204 USA.
   [Blackshear, Perry J.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA.
RP Mahat, DB (reprint author), Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA.
EM gwils001@umaryland.edu
FU American Cancer Society [RSG-07-293-01-GMC]; National Institutes of
   Heatlh [CA102428]; VA Merit Review Award
FX These studies were supported by American Cancer Society grant
   RSG-07-293-01-GMC and National Institutes of Heatlh grant CA102428 (to
   GMW) and by a VA Merit Review Award (to BAH). The funders had no role in
   study design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
NR 80
TC 7
Z9 7
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 MAR 8
PY 2012
VL 7
IS 3
AR e33194
DI 10.1371/journal.pone.0033194
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 929KT
UT WOS:000303062000036
PM 22413002
ER

PT J
AU Sundaresan, P
   Ravindran, RD
   Vashist, P
   Shanker, A
   Nitsch, D
   Talwar, B
   Maraini, G
   Camparini, M
   Nonyane, BAS
   Smeeth, L
   Chakravarthy, U
   Hejtmancik, JF
   Fletcher, AE
AF Sundaresan, Periasamy
   Ravindran, Ravilla D.
   Vashist, Praveen
   Shanker, Ashwini
   Nitsch, Dorothea
   Talwar, Badrinath
   Maraini, Giovanni
   Camparini, Monica
   Nonyane, Bareng Aletta S.
   Smeeth, Liam
   Chakravarthy, Usha
   Hejtmancik, James F.
   Fletcher, Astrid E.
TI EPHA2 Polymorphisms and Age-Related Cataract in India
SO PLOS ONE
LA English
DT Article
ID BEAVER DAM EYE; LENS OPACITIES; CORTICAL CATARACT; RISK-FACTORS;
   ASSOCIATION; POPULATION; DISEASES; NUCLEAR
AB Objective: We investigated whether previously reported single nucleotide polymorphisms (SNPs) of EPHA2 in European studies are associated with cataract in India.
   Methods: We carried out a population-based genetic association study. We enumerated randomly sampled villages in two areas of north and south India to identify people aged 40 and over. Participants attended a clinical examination including lens photography and provided a blood sample for genotyping. Lens images were graded by the Lens Opacification Classification System (LOCS III). Cataract was defined as a LOCS III grade of nuclear >= 4, cortical >= 3, posterior sub-capsular (PSC) >= 2, or dense opacities or aphakia/pseudophakia in either eye. We genotyped SNPs rs3754334, rs7543472 and rs11260867 on genomic DNA extracted from peripheral blood leukocytes using TaqMan assays in an ABI 7900 real-time PCR. We used logistic regression with robust standard errors to examine the association between cataract and the EPHA2 SNPs, adjusting for age, sex and location.
   Results: 7418 participants had data on at least one of the SNPs investigated. Genotype frequencies of controls were in Hardy-Weinberg Equilibrium (p > 0.05). There was no association of rs3754334 with cataract or type of cataract. Minor allele homozygous genotypes of rs7543472 and rs11260867 compared to the major homozygote genotype were associated with cortical cataract, Odds ratio (OR) = 1.8, 95% Confidence Interval (CI) (1.1, 3.1) p = 0.03 and 2.9 (1.2, 7.1) p = 0.01 respectively, and with PSC cataract, OR = 1.5 (1.1, 2.2) p = 0.02 and 1.8 (0.9, 3.6) p = 0.07 respectively. There was no consistent association of SNPs with nuclear cataract or a combined variable of any type of cataract including operated cataract.
   Conclusions: Our results in the Indian population agree with previous studies of the association of EPHA2 variants with cortical cataracts. We report new findings for the association with PSC which is particularly prevalent in Indians.
C1 [Sundaresan, Periasamy; Shanker, Ashwini] Aravind Eye Hosp, Dr G Venkataswamy Eye Res Inst, Dept Genet, Aravind Med Res Fdn, Madurai, Tamil Nadu, India.
   [Ravindran, Ravilla D.; Talwar, Badrinath] Aravind Eye Hosp, Pondicherry, India.
   [Vashist, Praveen] All India Inst Med Sci, Dr Rajendra Prasad Ctr Ophthalm Sci, New Delhi 110029, India.
   [Nitsch, Dorothea; Nonyane, Bareng Aletta S.; Smeeth, Liam; Fletcher, Astrid E.] London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, London WC1, England.
   [Maraini, Giovanni; Camparini, Monica] Univ Parma, Sez Oftalmol, Dipartimento Sci Otorino Odonto Oftalmol & Cerv F, I-43100 Parma, Italy.
   [Chakravarthy, Usha] Queens Univ Belfast, Ctr Vis & Vasc Sci, Sch Med Dent & Biomed Sci, Belfast BT7 1NN, Antrim, North Ireland.
   [Hejtmancik, James F.] NEI, Sect Ophthalm Mol Genet, Bethesda, MD 20892 USA.
RP Sundaresan, P (reprint author), Aravind Eye Hosp, Dr G Venkataswamy Eye Res Inst, Dept Genet, Aravind Med Res Fdn, Madurai, Tamil Nadu, India.
EM astrid.fletcher@lshtm.ac.uk
OI Nonyane, Bareng/0000-0001-5633-7487
FU Wellcome Trust [098504, G082571, 073300]
NR 18
TC 17
Z9 18
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 MAR 8
PY 2012
VL 7
IS 3
AR e33001
DI 10.1371/journal.pone.0033001
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 929KT
UT WOS:000303062000026
PM 22412971
ER

PT J
AU Li, ZJ
   Huang, H
   Li, YY
   Jiang, X
   Chen, P
   Arnovitz, S
   Radmacher, MD
   Maharry, K
   Elkahloun, A
   Yang, XN
   He, CJ
   He, M
   Zhang, ZY
   Dohner, K
   Neilly, MB
   Price, C
   Lussier, YA
   Zhang, YM
   Larson, RA
   Le Beau, MM
   Caligiuri, MA
   Bullinger, L
   Valk, PJM
   Delwel, R
   Lowenberg, B
   Liu, PP
   Marcucci, G
   Bloomfield, CD
   Rowley, JD
   Chen, JJ
AF Li, Zejuan
   Huang, Hao
   Li, Yuanyuan
   Jiang, Xi
   Chen, Ping
   Arnovitz, Stephen
   Radmacher, Michael D.
   Maharry, Kati
   Elkahloun, Abdel
   Yang, Xinan
   He, Chunjiang
   He, Miao
   Zhang, Zhiyu
   Dohner, Konstanze
   Neilly, Mary Beth
   Price, Colles
   Lussier, Yves A.
   Zhang, Yanming
   Larson, Richard A.
   Le Beau, Michelle M.
   Caligiuri, Michael A.
   Bullinger, Lars
   Valk, Peter J. M.
   Delwel, Ruud
   Lowenberg, Bob
   Liu, Paul P.
   Marcucci, Guido
   Bloomfield, Clara D.
   Rowley, Janet D.
   Chen, Jianjun
TI Up-regulation of a HOXA-PBX3 homeobox-gene signature following
   down-regulation of miR-181 is associated with adverse prognosis in
   patients with cytogenetically abnormal AML
SO BLOOD
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; MICRORNA EXPRESSION; TRANSCRIPTION FACTORS;
   CLASS PREDICTION; CEBPA MUTATIONS; HOX EXPRESSION; TARGETING HOX;
   GROUP-B; MLL; CANCER
AB Increased expression levels of miR-181 family members have been shown to be associated with favorable outcome in patients with cytogenetically normal acute myeloid leukemia. Here we show that increased expression of miR-181a and miR-181b is also significantly (P < .05; Cox regression) associated with favorable overall survival in cytogenetically abnormal AML (CA-AML) patients. We further show that up-regulation of a gene signature composed of 4 potential miR-181 targets (including HOXA7, HOXA9, HOXA11, and PBX3), associated with down-regulation of miR-181 family members, is an independent predictor of adverse overall survival on multivariable testing in analysis of 183 CA-AML patients. The independent prognostic impact of this 4-homeobox-gene signature was confirmed in a validation set of 271 CA-AML patients. Furthermore, our in vitro and in vivo studies indicated that ectopic expression of miR-181b significantly promoted apoptosis and inhibited viability/proliferation of leukemic cells and delayed leukemogenesis; such effects could be reversed by forced expression of PBX3. Thus, the up-regulation of the 4 homeobox genes resulting from the down-regulation of miR-181 family members probably contribute to the poor prognosis of patients with nonfavorable CA-AML. Restoring expression of miR-181b and/or targeting the HOXA/PBX3 pathways may provide new strategies to improve survival substantially. (Blood. 2012;119(10):2314-2324)
C1 [Li, Zejuan; Huang, Hao; Li, Yuanyuan; Jiang, Xi; Chen, Ping; Arnovitz, Stephen; He, Chunjiang; He, Miao; Neilly, Mary Beth; Price, Colles; Zhang, Yanming; Larson, Richard A.; Le Beau, Michelle M.; Rowley, Janet D.; Chen, Jianjun] Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA.
   [Radmacher, Michael D.; Maharry, Kati; Caligiuri, Michael A.; Marcucci, Guido; Bloomfield, Clara D.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA.
   [Elkahloun, Abdel; Liu, Paul P.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
   [Yang, Xinan; Lussier, Yves A.] Univ Chicago, Dept Med, Ctr Biomed Informat, Med Genet Sect, Chicago, IL 60637 USA.
   [Zhang, Zhiyu] Univ Chicago, Tang Ctr Herbal Med Res, Chicago, IL 60637 USA.
   [Dohner, Konstanze; Bullinger, Lars] Univ Ulm, Dept Internal Med 3, D-7900 Ulm, Germany.
   [Valk, Peter J. M.; Delwel, Ruud; Lowenberg, Bob] Erasmus Univ, Med Ctr, Dept Hematol, Rotterdam, Netherlands.
RP Chen, JJ (reprint author), Univ Chicago, Dept Med, Hematol Oncol Sect, 900 E 57th St,KCBD Rm 7134, Chicago, IL 60637 USA.
EM jchen@medicine.bsd.uchicago.edu
RI Liu, Paul/A-7976-2012; 
OI Liu, Paul/0000-0002-6779-025X; He, Chunjiang/0000-0002-4868-331X;
   Lussier, Yves/0000-0001-9854-1005; Larson, Richard/0000-0001-9168-3203
FU Leukemia & Lymphoma Society; CALGB [20801]; National Institutes of
   Health [CA127277, P01 CA40046, P30 CA014599]; American Cancer Society;
   Gabrielle's Angel Foundation for Cancer Research; Spastic Paralysis
   Foundation of the Illinois, Eastern Iowa Branch of Kiwanis
   International; Fidelity Foundation; U10 of the CALGB LCSC committee [U10
   CA101140]; P50 of OSU Leukemia SPORE [P50CA140158]; Leukemia Clinical
   Research Foundation; National Human Genome Research Institute, National
   Institutes of Health; National Natural Science Foundation of China
   [60971099]; Deutsche Jose Carreras Leukamie Stiftung [R 06/41v];
   Deutsche Forschungsgemeinschaft (Heisenberg-Stipendium) [BU 1339/3-1]
FX This work was supported in part by the Leukemia & Lymphoma Society
   (Translational Research Grant, J.D.R. and J.C.), CALGB (pilot grant
   20801, J.D.R. and J.C.), National Institutes of Health (R01 grant
   CA127277, J.C.), American Cancer Society (Research Scholar grant, J.C.),
   Leukemia & Lymphoma Society (Special Fellowship, Z.L.), Gabrielle's
   Angel Foundation for Cancer Research (J.C., Z.L., and H. H.), the
   Spastic Paralysis Foundation of the Illinois, Eastern Iowa Branch of
   Kiwanis International (J.D.R.), the Fidelity Foundation (J.D.R. and
   J.C.), the U10 of the CALGB LCSC committee (U10 CA101140, G.M.), the P50
   of OSU Leukemia SPORE (P50CA140158 Project 2, C.D.B. and G.M.), Leukemia
   Clinical Research Foundation grant (C.D.B. and G.M), the Intramural
   Research Program of National Human Genome Research Institute, National
   Institutes of Health (A.E. and P.P.L.), the National Natural Science
   Foundation of China (60971099, X.Y.),the Deutsche Jose Carreras Leukamie
   Stiftung (grant R 06/41v, L.B.), the Deutsche Forschungsgemeinschaft
   (Heisenberg-Stipendium BU 1339/3-1, L.B), and National Institutes of
   Health (P01 CA40046, M.M.L.B.; and P30 CA014599, M.M.L.B.).
NR 50
TC 75
Z9 84
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 MAR 8
PY 2012
VL 119
IS 10
BP 2314
EP 2324
DI 10.1182/blood-2011-10-386235
PG 11
WC Hematology
SC Hematology
GA 906OP
UT WOS:000301356000022
PM 22251480
ER

PT J
AU Little, MP
   Rajaraman, P
   Curtis, RE
   Devesa, SS
   Inskip, PD
   Check, DP
   Linet, MS
AF Little, M. P.
   Rajaraman, P.
   Curtis, R. E.
   Devesa, S. S.
   Inskip, P. D.
   Check, D. P.
   Linet, M. S.
TI Mobile phone use and glioma risk: comparison of epidemiological study
   results with incidence trends in the United States
SO BRITISH MEDICAL JOURNAL
LA English
DT Article
ID CELLULAR-TELEPHONE USE; MALIGNANT BRAIN-TUMORS; CORDLESS PHONES;
   INCIDENCE RATES; DANISH COHORT; TIME TRENDS; CANCER; CLONALITY;
   RADIATION; DENMARK
AB Objective In view of mobile phone exposure being classified as a possible human carcinogen by the International Agency for Research on Cancer (IARC), we determined the compatibility of two recent reports of glioma risk (forming the basis of the IARC's classification) with observed incidence trends in the United States.
   Design Comparison of observed rates with projected rates of glioma incidence for 1997-2008. We estimated projected rates by combining relative risks reported in the 2010 Interphone study and a 2011 Swedish study by Hardell and colleagues with rates adjusted for age, registry, and sex; data for mobile phone use; and various latency periods.
   Setting US population based data for glioma incidence in 1992-2008, from 12 registries in the Surveillance, Epidemiology, and End Results (SEER) programme (Atlanta, Detroit, Los Angeles, San Francisco, San Jose-Monterey, Seattle, rural Georgia, Connecticut, Hawaii, Iowa, New Mexico, and Utah).
   Participants Data for 24 813 non-Hispanic white people diagnosed with glioma at age 18 years or older.
   Results Age specific incidence rates of glioma remained generally constant in 1992-2008 (-0.02% change per year, 95% confidence interval -0.28% to 0.25%), a period coinciding with a substantial increase in mobile phone use from close to 0% to almost 100% of the US population. If phone use was associated with glioma risk, we expected glioma incidence rates to be higher than those observed, even with a latency period of 10 years and low relative risks (1.5). Based on relative risks of glioma by tumour latency and cumulative hours of phone use in the Swedish study, predicted rates should have been at least 40% higher than observed rates in 2008. However, predicted glioma rates based on the small proportion of highly exposed people in the Interphone study could be consistent with the observed data. Results remained valid if we used either non-regular users or low users of mobile phones as the baseline category, and if we constrained relative risks to be more than 1.
   Conclusions Raised risks of glioma with mobile phone use, as reported by one (Swedish) study forming the basis of the IARC's re-evaluation of mobile phone exposure, are not consistent with observed incidence trends in US population data, although the US data could be consistent with the modest excess risks in the Interphone study.
C1 [Little, M. P.; Rajaraman, P.; Curtis, R. E.; Inskip, P. D.; Linet, M. S.] NCI, Radiat Epidemiol Branch, Rockville, MD 20852 USA.
   [Devesa, S. S.; Check, D. P.] NCI, Biostat Branch, Rockville, MD 20852 USA.
RP Little, MP (reprint author), NCI, Radiat Epidemiol Branch, Rockville, MD 20852 USA.
EM mark.little@nih.gov
OI Little, Mark/0000-0003-0980-7567
FU National Institutes of Health; National Cancer Institute, Division of
   Cancer Epidemiology and Genetics
FX This work was supported by the Intramural Research Program of the
   National Institutes of Health, and the National Cancer Institute,
   Division of Cancer Epidemiology and Genetics.
NR 40
TC 42
Z9 44
U1 2
U2 32
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 MAR 8
PY 2012
VL 344
AR e1147
DI 10.1136/bmj.e1147
PG 16
WC Medicine, General & Internal
SC General & Internal Medicine
GA 908HL
UT WOS:000301481400001
PM 22403263
ER

PT J
AU Andreani, A
   Granaiola, M
   Locatelli, A
   Morigi, R
   Rambaldi, M
   Varoli, L
   Calonghi, N
   Cappadone, C
   Farruggia, G
   Stefanelli, C
   Masotti, L
   Nguyen, TL
   Hamel, E
   Shoemaker, RH
AF Andreani, Aldo
   Granaiola, Massimiliano
   Locatelli, Alessandra
   Morigi, Rita
   Rambaldi, Mirella
   Varoli, Lucilla
   Calonghi, Natalia
   Cappadone, Concettina
   Farruggia, Giovanna
   Stefanelli, Claudio
   Masotti, Lanfranco
   Nguyen, Tam L.
   Hamel, Ernest
   Shoemaker, Robert H.
TI Substituted 3-(5-Imidazo[2,1-b]thiazolylmethylene)-2-indolinones and
   Analogues: Synthesis, Cytotoxic Activity, and Study of the Mechanism of
   Action
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID POTENTIAL ANTITUMOR AGENTS; ANTIMITOTIC AGENTS; CANCER-CELLS; TUBULIN;
   GUANYLHYDRAZONES; DERIVATIVES; INHIBITORS; COLCHICINE; APOPTOSIS; GROWTH
AB The synthesis of substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones and analogues is reported. Their cytotoxic activity was evaluated according to protocols available at the National Cancer Institute (NCI), Bethesda, MD. The action of selected compounds was examined for potential inhibition of tubulin assembly in comparison with the potent colchicine site agent combretastatin A-4. The most potent compounds also strongly and selectively inhibited the phosphorylation of the oncoprotein kinase Akt in cancer cells. The effect of the most interesting compounds was examined on the growth of HT-29 colon cancer cells. These compounds caused the cells to arrest in the G2/M phase of the cell cycle, as would be expected for inhibitors of tubulin assembly.
C1 [Andreani, Aldo; Granaiola, Massimiliano; Locatelli, Alessandra; Morigi, Rita; Rambaldi, Mirella; Varoli, Lucilla] Univ Bologna, Dipartimento Sci Farmaceut, I-40126 Bologna, Italy.
   [Calonghi, Natalia; Cappadone, Concettina; Farruggia, Giovanna; Stefanelli, Claudio; Masotti, Lanfranco] Univ Bologna, Dipartimento Biochim G Moruzzi, I-40126 Bologna, Italy.
   [Nguyen, Tam L.] NCI, Target Struct Based Drug Discovery Grp, SAIC Frederick Inc, Frederick, MD 21702 USA.
   [Hamel, Ernest; Shoemaker, Robert H.] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA.
RP Andreani, A (reprint author), Univ Bologna, Dipartimento Sci Farmaceut, Via Belmeloro 6, I-40126 Bologna, Italy.
EM aldo.andreani@unibo.it
FU University of Bologna, Italy (RFO); MIUR; National Cancer Institute,
   National Institutes of Health [N01-CO-12400]; Division of Cancer
   Treatment and Diagnosis of the National Cancer Institute
FX This work was supported in part by a grant from the University of
   Bologna, Italy (RFO), and from MIUR (PRIN 2009). We are grateful to the
   National Cancer Institute (Bethesda, MD) for the anticancer tests. It
   has been funded in part with federal funds from the National Cancer
   Institute, National Institutes of Health, under contract N01-CO-12400.
   The content of this publication does not necessarily reflect the views
   or policies of the Department of Health and Human Services, nor does
   mention of trade names, commercial products, or organizations imply
   endorsement by the U.S. Government. This research was supported in part
   by the Developmental Therapeutics Program in the Division of Cancer
   Treatment and Diagnosis of the National Cancer Institute.
NR 42
TC 26
Z9 26
U1 0
U2 16
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 MAR 8
PY 2012
VL 55
IS 5
BP 2078
EP 2088
DI 10.1021/jm2012694
PG 11
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 904CA
UT WOS:000301170000025
PM 22283430
ER

PT J
AU Bao, XF
   Lu, SY
   Liow, JS
   Zoghbi, SS
   Jenko, KJ
   Clark, DT
   Gladding, RL
   Innis, RB
   Pike, VW
AF Bao, Xiaofeng
   Lu, Shuiyu
   Liow, Jeih-San
   Zoghbi, Sami S.
   Jenko, Kimberly J.
   Clark, David T.
   Gladding, Robert L.
   Innis, Robert B.
   Pike, Victor W.
TI Radiosynthesis and Evaluation of an F-18-Labeled Positron Emission
   Tomography (PET) Radioligand for Brain Histamine Subtype-3 Receptors
   Based on a Nonimidazole 2-Aminoethylbenzofuran Chemotype
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID H-3 RECEPTOR; IN-VIVO; RAT-BRAIN; FREE-FRACTION; H3 RECEPTOR;
   ANTAGONIST; BINDING; LIGAND; BIODISTRIBUTION; LOCALIZATION
AB A known chemotype of H-3 receptor ligand was explored for development of a radioligand for imaging brain histamine subtype 3 (H-3) receptors in vivo with positron emission tomography (PET), namely nonimidazole 2-aminoethylbenzofurans, represented by the compound (R)-(2-(2-(2-methylpyrrolidin-1-yl)ethyl)benzofuran-5-yl)(4-fluorophenyl)-methanone (9). Compound 9 was labeled with fluorine-18 (t(1/2) = 109.7 min) in high specific activity by treating the prepared nitro analogue (12) with cyclotron-produced [F-18]-fluoride ion. [F-18]9 was studied with PET in mouse and in monkey after intravenous injection. [F-18]9 showed favorable properties as a candidate PET radioligand, including moderately high brain uptake with a high proportion of H-3 receptor-specific signal in the absence of radiodefluorination. The nitro compound 12 was found to have even higher H-3 receptor affinity, indicating the potential of this chemotype for the development of further promising PET ralioligands.
C1 [Bao, Xiaofeng; Lu, Shuiyu; Liow, Jeih-San; Zoghbi, Sami S.; Jenko, Kimberly J.; Clark, David T.; Gladding, Robert L.; Innis, Robert B.; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
RP Pike, VW (reprint author), NIMH, Mol Imaging Branch, NIH, Bldg 10,Room B3 C346A,10 Ctr Dr, Bethesda, MD 20892 USA.
EM pikev@mail.nih.gov
RI Bao, Xiaofeng/K-5278-2013; 
OI Lu, Shuiyu/0000-0003-0310-4318
FU National Institutes of Health (NIMH) [HHSN-271-2008-00025-C]
FX This study was supported by the Intramural Research Program of the
   National Institutes of Health (NIMH). We thank the NIH Clinical PET
   Department (Chief Dr. P. Herscovitch) for fluorine-18 production and
   PMOD Technologies for providing the image analysis software. Receptor
   binding assays were performed by the National Institute of Mental
   Health's Psychoactive Drug Screening Program, contract no.
   HHSN-271-2008-00025-C (NIMH PDSP). The NIMH PDSP is directed by Dr.
   Bryan L. Roth, MD Ph.D., at the University of North Carolina at Chapel
   Hill and Project Officer Jamie Driscoll at NIMH, Bethesda, MD, USA. We
   also thank Cheryl L. Morse (NIMH) for assistance in radiochemistry.
NR 44
TC 15
Z9 15
U1 0
U2 13
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 MAR 8
PY 2012
VL 55
IS 5
BP 2406
EP 2415
DI 10.1021/jm201690h
PG 10
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 904CA
UT WOS:000301170000051
PM 22313227
ER

PT J
AU Savitz, J
   Nugent, AC
   Cannon, DM
   Carlson, PJ
   Davis, R
   Neumeister, A
   Rallis-Frutos, D
   Fromm, S
   Herscovitch, P
   Drevets, WC
AF Savitz, Jonathan
   Nugent, Allison C.
   Cannon, Dara M.
   Carlson, Paul J.
   Davis, Rebecca
   Neumeister, Alexander
   Rallis-Frutos, Denise
   Fromm, Steve
   Herscovitch, Peter
   Drevets, Wayne C.
TI Effects of arterial cannulation stress on regional cerebral blood flow
   in major depressive disorder
SO SCIENTIFIC REPORTS
LA English
DT Article
ID MEDIAL PREFRONTAL CORTEX; POSITRON-EMISSION-TOMOGRAPHY; ANTERIOR
   CINGULATE CORTEX; DEFAULT-MODE NETWORK; PAINFUL STIMULATION; HIPPOCAMPAL
   VOLUME; GLUCOSE-METABOLISM; BIPOLAR DISORDER; BRAIN ACTIVATION;
   CORTISOL-LEVELS
AB Individuals with major depressive disorder (MDD) display abnormal neurophysiological responses to psychological stress but little is known about their neurophysiological responses to physiological stressors. Using [O-15]-H2O positron emission tomography we assessed whether the regional cerebral blood flow (rCBF) response to arterial cannulation differed between patients with MDD and healthy controls (HCs). Fifty-one MDDpatients and 62 HCs were scanned following arterial cannulation and 15MDDpatients and 17 HCs were scanned without arterial cannulation. A region-of-interest analysis showed that a significantly increased rCBF of the anterior cingulate cortex and right amygdala was associated with arterial cannulation in MDD. A whole brain analysis showed increased rCBF of the right post-central gyrus, left temporopolar cortex, and right amygdala during arterial cannulation in MDD patients. The rCBF in the right amygdala was significantly correlated with depression severity. Conceivably, the limbic response to invasive physical stress is greater in MDD subjects than in HCs.
C1 [Savitz, Jonathan; Nugent, Allison C.; Davis, Rebecca; Rallis-Frutos, Denise; Fromm, Steve; Drevets, Wayne C.] NIMH, Sect Neuroimaging Mood & Anxiety Disorders, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
   [Savitz, Jonathan; Drevets, Wayne C.] Laureate Inst Brain Res, Tulsa, OK USA.
   [Savitz, Jonathan] Tulsa Sch Community Med, Dept Med, Tulsa, OK USA.
   [Nugent, Allison C.] NIMH, Expt Therapeut Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
   [Cannon, Dara M.] Natl Univ Ireland Galway, Clin Neuroimaging Lab, Galway, Ireland.
   [Carlson, Paul J.] Univ Utah, Salt Lake City VA, Salt Lake City, UT USA.
   [Carlson, Paul J.] Univ Utah, Dept Psychiat, Salt Lake City, UT USA.
   [Neumeister, Alexander] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA.
   [Herscovitch, Peter] NIH, Ctr Clin, Bethesda, MD 20892 USA.
   [Drevets, Wayne C.] Univ Oklahoma, Coll Med, Dept Psychiat, Tulsa, OK USA.
RP Savitz, J (reprint author), NIMH, Sect Neuroimaging Mood & Anxiety Disorders, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
EM jonathansavitz@hotmail.com
RI Savitz, Jonathan/C-3088-2009; Cannon, Dara/C-1323-2009; 
OI Savitz, Jonathan/0000-0001-8143-182X; Cannon, Dara/0000-0001-7378-3411;
   Nugent, Allison/0000-0003-2569-2480
NR 98
TC 2
Z9 2
U1 2
U2 2
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 MAR 8
PY 2012
VL 2
AR 308
DI 10.1038/srep00308
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 905TX
UT WOS:000301299000002
PM 22403745
ER

PT J
AU Scally, A
   Dutheil, JY
   Hillier, LW
   Jordan, GE
   Goodhead, I
   Herrero, J
   Hobolth, A
   Lappalainen, T
   Mailund, T
   Marques-Bonet, T
   McCarthy, S
   Montgomery, SH
   Schwalie, PC
   Tang, YA
   Ward, MC
   Xue, YL
   Yngvadottir, B
   Alkan, C
   Andersen, LN
   Ayub, Q
   Ball, EV
   Beal, K
   Bradley, BJ
   Chen, Y
   Clee, CM
   Fitzgerald, S
   Graves, TA
   Gu, Y
   Heath, P
   Heger, A
   Karakoc, E
   Kolb-Kokocinski, A
   Laird, GK
   Lunter, G
   Meader, S
   Mort, M
   Mullikin, JC
   Munch, K
   O'Connor, TD
   Phillips, AD
   Prado-Martinez, J
   Rogers, AS
   Sajjadian, S
   Schmidt, D
   Shaw, K
   Simpson, JT
   Stenson, PD
   Turner, DJ
   Vigilant, L
   Vilella, AJ
   Whitener, W
   Zhu, BL
   Cooper, DN
   de Jong, P
   Dermitzakis, ET
   Eichler, EE
   Flicek, P
   Goldman, N
   Mundy, NI
   Ning, ZM
   Odom, DT
   Ponting, CP
   Quail, MA
   Ryder, OA
   Searle, SM
   Warren, WC
   Wilson, RK
   Schierup, MH
   Rogers, J
   Tyler-Smith, C
   Durbin, R
AF Scally, Aylwyn
   Dutheil, Julien Y.
   Hillier, LaDeana W.
   Jordan, Gregory E.
   Goodhead, Ian
   Herrero, Javier
   Hobolth, Asger
   Lappalainen, Tuuli
   Mailund, Thomas
   Marques-Bonet, Tomas
   McCarthy, Shane
   Montgomery, Stephen H.
   Schwalie, Petra C.
   Tang, Y. Amy
   Ward, Michelle C.
   Xue, Yali
   Yngvadottir, Bryndis
   Alkan, Can
   Andersen, Lars N.
   Ayub, Qasim
   Ball, Edward V.
   Beal, Kathryn
   Bradley, Brenda J.
   Chen, Yuan
   Clee, Chris M.
   Fitzgerald, Stephen
   Graves, Tina A.
   Gu, Yong
   Heath, Paul
   Heger, Andreas
   Karakoc, Emre
   Kolb-Kokocinski, Anja
   Laird, Gavin K.
   Lunter, Gerton
   Meader, Stephen
   Mort, Matthew
   Mullikin, James C.
   Munch, Kasper
   O'Connor, Timothy D.
   Phillips, Andrew D.
   Prado-Martinez, Javier
   Rogers, Anthony S.
   Sajjadian, Saba
   Schmidt, Dominic
   Shaw, Katy
   Simpson, Jared T.
   Stenson, Peter D.
   Turner, Daniel J.
   Vigilant, Linda
   Vilella, Albert J.
   Whitener, Weldon
   Zhu, Baoli
   Cooper, David N.
   de Jong, Pieter
   Dermitzakis, Emmanouil T.
   Eichler, Evan E.
   Flicek, Paul
   Goldman, Nick
   Mundy, Nicholas I.
   Ning, Zemin
   Odom, Duncan T.
   Ponting, Chris P.
   Quail, Michael A.
   Ryder, Oliver A.
   Searle, Stephen M.
   Warren, Wesley C.
   Wilson, Richard K.
   Schierup, Mikkel H.
   Rogers, Jane
   Tyler-Smith, Chris
   Durbin, Richard
TI Insights into hominid evolution from the gorilla genome sequence
SO NATURE
LA English
DT Article
ID COPY NUMBER; MUTATION; POPULATION; PRIMATES; HUMANS; CONSEQUENCES;
   CHIMPANZEES; PATTERNS; REVEALS; FAMILY
AB Gorillas are humans' closest living relatives after chimpanzees, and are of comparable importance for the study of human origins and evolution. Here we present the assembly and analysis of a genome sequence for the western lowland gorilla, and compare the whole genomes of all extant great ape genera. We propose a synthesis of genetic and fossil evidence consistent with placing the human-chimpanzee and human-chimpanzee-gorilla speciation events at approximately 6 and 10 million years ago. In 30% of the genome, gorilla is closer to human or chimpanzee than the latter are to each other; this is rarer around coding genes, indicating pervasive selection throughout great ape evolution, and has functional consequences in gene expression. A comparison of protein coding genes reveals approximately 500 genes showing accelerated evolution on each of the gorilla, human and chimpanzee lineages, and evidence for parallel acceleration, particularly of genes involved in hearing. We also compare the western and eastern gorilla species, estimating an average sequence divergence time 1.75 million years ago, but with evidence for more recent genetic exchange and a population bottleneck in the eastern species. The use of the genome sequence in these and future analyses will promote a deeper understanding of great ape biology and evolution.
C1 [Scally, Aylwyn; Goodhead, Ian; McCarthy, Shane; Tang, Y. Amy; Xue, Yali; Yngvadottir, Bryndis; Ayub, Qasim; Chen, Yuan; Clee, Chris M.; Gu, Yong; Heath, Paul; Kolb-Kokocinski, Anja; Laird, Gavin K.; Rogers, Anthony S.; Simpson, Jared T.; Turner, Daniel J.; Whitener, Weldon; Ning, Zemin; Odom, Duncan T.; Quail, Michael A.; Searle, Stephen M.; Rogers, Jane; Tyler-Smith, Chris; Durbin, Richard] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England.
   [Dutheil, Julien Y.; Hobolth, Asger; Mailund, Thomas; Andersen, Lars N.; Munch, Kasper; Schierup, Mikkel H.] Aarhus Univ, Bioinformat Res Ctr, DK-8000 Aarhus C, Denmark.
   [Hillier, LaDeana W.; Marques-Bonet, Tomas; Alkan, Can; Karakoc, Emre; Sajjadian, Saba; Eichler, Evan E.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA.
   [Jordan, Gregory E.; Herrero, Javier; Schwalie, Petra C.; Beal, Kathryn; Fitzgerald, Stephen; Vilella, Albert J.; Flicek, Paul; Goldman, Nick] European Bioinformat Inst, Hinxton CB10 1SD, England.
   [Lappalainen, Tuuli; Dermitzakis, Emmanouil T.] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva 4, Switzerland.
   [Marques-Bonet, Tomas; Prado-Martinez, Javier] Inst Biol Evolut UPF CSIC, Barcelona 08003, Catalonia, Spain.
   [Marques-Bonet, Tomas] ICREA, Barcelona 08010, Spain.
   [Montgomery, Stephen H.; Bradley, Brenda J.; O'Connor, Timothy D.; Mundy, Nicholas I.] Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England.
   [Ward, Michelle C.; Schmidt, Dominic; Odom, Duncan T.] Univ Cambridge, Dept Oncol, Hutchison MRC Res Ctr, Cambridge CB2 0XZ, England.
   [Ward, Michelle C.; Schmidt, Dominic; Odom, Duncan T.] Cambridge Res Inst, Canc Res UK, Li Ka Shing Ctr, Cambridge CB2 0RE, England.
   [Alkan, Can; Eichler, Evan E.] Univ Washington, Howard Hughes Med Inst, Seattle, WA USA.
   [Ball, Edward V.; Mort, Matthew; Phillips, Andrew D.; Shaw, Katy; Stenson, Peter D.; Cooper, David N.] Cardiff Univ, Inst Med Genet, Cardiff CF14 4XN, S Glam, Wales.
   [Bradley, Brenda J.] Yale Univ, Dept Anthropol, New Haven, CT 06511 USA.
   [Graves, Tina A.; Warren, Wesley C.; Wilson, Richard K.] Washington Univ, Sch Med, Genome Inst, St Louis, MO 63108 USA.
   [Heger, Andreas; Meader, Stephen; Ponting, Chris P.] Univ Oxford, Dept Physiol Anat & Genet, MRC Funct Genom Unit, Oxford OX1 3QX, England.
   [Lunter, Gerton] Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Mullikin, James C.] NHGRI, Comparat Genom Unit, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
   [Vigilant, Linda] Max Planck Inst Evolutionary Anthropol, Primatol Dept, D-04103 Leipzig, Germany.
   [Zhu, Baoli; de Jong, Pieter] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA.
   [Ryder, Oliver A.] San Diego Zoos Inst Conservat Res, Escondido, CA 92027 USA.
RP Durbin, R (reprint author), Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton CB10 1SA, England.
EM rd@sanger.ac.uk
RI Alkan, Can/D-2982-2009; Munch, Kasper/A-1434-2010; Dermitzakis,
   Emmanouil/B-7687-2013; Ning, Zemin/D-2411-2013; Marques-Bonet,
   Tomas/I-4618-2014; Schierup, Mikkel/F-1675-2010; Cooper,
   David/H-4384-2011; Lunter, Gerton/H-4939-2016; Dutheil,
   Julien/K-5479-2016; 
OI Alkan, Can/0000-0002-5443-0706; Goodhead, Ian/0000-0002-3110-9442;
   Munch, Kasper/0000-0003-2880-6252; Marques-Bonet,
   Tomas/0000-0002-5597-3075; Schierup, Mikkel/0000-0002-5028-1790; Cooper,
   David/0000-0002-8943-8484; Dutheil, Julien/0000-0001-7753-4121; Odom,
   Duncan/0000-0001-6201-5599; Jordan, Gregory/0000-0002-7655-6000; Durbin,
   Richard/0000-0002-9130-1006; Prado-Martinez, Javier/0000-0001-5402-2721;
   Schwalie, Petra Catalina/0000-0002-6004-8095; Lappalainen,
   Tuuli/0000-0002-7746-8109; Mailund, Thomas/0000-0001-6206-9239; Vilella,
   Albert/0000-0002-2005-2516; Lunter, Gerton/0000-0002-3798-2058; Ayub,
   Qasim/0000-0003-3291-0917; Ning, Zemin/0000-0003-4359-776X; Herrero,
   Javier/0000-0001-7313-717X; Goldman, Nick/0000-0001-8486-2211; Flicek,
   Paul/0000-0002-3897-7955; Tang, Amy/0000-0003-0045-1234; Ponting,
   Chris/0000-0003-0202-7816; Hobolth, Asger/0000-0003-4056-1286; McCarthy,
   Shane/0000-0002-2715-4187; Heger, Andreas/0000-0001-7720-0447
FU Wellcome Trust [WT062023, WT089066, WT077192, WT077009, WT077198,
   075491/Z/04]; EMBL; Gates Cambridge Trust; MRC; Lundbeck Foundation;
   Academy of Finlandand the Emil Aaltonen Foundation; Marie Curie
   fellowship; European Community [StG_20091118]; Spanish Ministry of
   Education [BES-2010-032251]; BBSRC; UK Medical Research Council;
   National Human Genome Research Institute, National Institutes of Health;
   Danish Council for Independent Research, Natural Sciences [09-062535];
   Commonwealth Scholarship; Swiss National Science Foundation; Louis
   Jeantet Foundation; ERC; EMBO; Hutchinson Whampoa; NHGRI; BIOBASE GmbH;
   US National Science Foundation [DGE-0739133]; NHGRI [U54 HG003079]; NIH
   [HG002385]
FX We thank H. Li and E. Birney for discussions, D. Zerbino, J. Stalker, L.
   Wilming, D. Rajan and H. Clawson for technical assistance, J. Ahringer
   for comments on the manuscript, K. Leus of the Center for Research and
   Conservation of the Royal Zoological Society of Antwerp for sample
   material from Mukisi, and the Marmoset Genome Analysis Consortium for
   permission to use the unpublished assembly of the marmoset genome. This
   research was supported in part by Wellcome Trust grants WT062023 (to
   J.H., K.B., S.F., A.J.V., P.F.), WT089066 (to R.D.), WT077192 (to R.D.,
   S.M., A.K.-K., J.T.S., W.W.), WT077009 (to Y.X., B.Y., Q A., Y.C.,
   C.T.-S.), WT077198 (to G.K.L.) and 075491/Z/04 (to G.L.); EMBL grants
   (to P.C.S., P.F.); scholarships from the Gates Cambridge Trust (to
   G.E.J. and T.D.O'C.); an MRC Special Fellowship in Biomedical
   Informatics (to A.S.); funding from the Lundbeck Foundation (to A.H.);
   the Academy of Finlandand the Emil Aaltonen Foundation (to T.L.); a
   Marie Curie fellowship (to T.M.-B.); the European Community's Seventh
   Framework Programme (FP7/2007-2013)/ERC Starting Grant (StG_20091118)
   (to T.M.-B.); an FPI grant from the Spanish Ministry of Education
   (BES-2010-032251) (to J.P.-M.); a BBSRC Doctoral Training Grant (to
   S.H.M.); grants from the UK Medical Research Council (to A.H., S.M.,
   C.P.P.); the Intramural Research Program of the National Human Genome
   Research Institute, National Institutes of Health (to J.C.M.); the
   Danish Council for Independent Research, Natural Sciences, grant no.
   09-062535 (to K.M., M.H.S.); a Commonwealth Scholarship (to M.C.W.); the
   Swiss National Science Foundation, Louis Jeantet Foundation (to E.T.D.);
   an ERC Starting Grant and an EMBO Young Investigator Award, Hutchinson
   Whampoa (to D.T.O.); NHGRI support (to W.C.W.); support from BIOBASE
   GmbH (to E.V.B., P.D.S., M.M., A.D.P., K.S., D.N.C.); US National
   Science Foundation grant DGE-0739133 (to W.W.); NHGRI U54 HG003079 (to
   R.K.W.); NIH grant HG002385 (to E.E.E). E.E.E. is an investigator of the
   Howard Hughes Medical Institute.
NR 51
TC 258
Z9 262
U1 13
U2 129
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD MAR 8
PY 2012
VL 483
IS 7388
BP 169
EP 175
DI 10.1038/nature10842
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 904DT
UT WOS:000301174900029
PM 22398555
ER

PT J
AU Ngamskulrungroj, P
   Chang, Y
   Hansen, B
   Bugge, C
   Fischer, E
   Kwon-Chung, KJ
AF Ngamskulrungroj, Popchai
   Chang, Yun
   Hansen, Bryan
   Bugge, Cliff
   Fischer, Elizabeth
   Kwon-Chung, Kyung J.
TI Characterization of the Chromosome 4 Genes That Affect
   Fluconazole-Induced Disomy Formation in Cryptococcus neoformans
SO PLOS ONE
LA English
DT Article
ID ENDOPLASMIC-RETICULUM STRESS; AMINO-ACID SUBSTITUTIONS; AZOLE ANTIFUNGAL
   AGENTS; CANDIDA-ALBICANS; SACCHAROMYCES-CEREVISIAE; DRUG-RESISTANCE;
   RETROGRADE TRANSPORT; NUCLEAR-ENVELOPE; YEAST; IDENTIFICATION
AB Heteroresistance in Cryptococcus neoformans is an intrinsic adaptive resistance to azoles and the heteroresistant phenotype is associated with disomic chromosomes. Two chromosome 1 (Chr1) genes, ERG11, the fluconazole target, and AFR1, a drug transporter, were reported as major factors in the emergence of Chr1 disomy. In the present study, we show Chr4 to be the second most frequently formed disomy at high concentrations of fluconazole (FLC) and characterize the importance of resident genes contributing to disomy formation. We deleted nine Chr4 genes presumed to have functions in ergosterol biosynthesis, membrane composition/integrity or drug transportation that could influence Chr4 disomy under FLC stress. Of these nine, disruption of three genes homologous to Sey1 (a GTPase), Glo3 and Gcs2 (the ADP-ribosylation factor GTPase activating proteins) significantly reduced the frequency of Chr4 disomy in heteroresistant clones. Furthermore, FLC resistant clones derived from sey1 Delta glo3 Delta did not show disomy of either Chr4 or Chr1 but instead had increased the copy number of the genes proximal to ERG11 locus on Chr1. Since the three genes are critical for the integrity of endoplasmic reticulum (ER) in Saccharomyces cerevisiae, we used Sec61 beta-GFP fusion as a marker to study the ER in the mutants. The cytoplasmic ER was found to be elongated in sey1D but without any discernable alteration in gcs2 Delta and glo3 Delta under fluorescence microscopy. The aberrant ER morphology of all three mutant strains, however, was discernable by transmission electron microscopy. A 3D reconstruction using Focused Ion Beam Scanning Electron Microscopy (FIB-SEM) revealed considerably reduced reticulation in the ER of glo3 Delta and gcs2 Delta strains. In sey1 Delta, ER reticulation was barely detectable and cisternae were expanded extensively compared to the wild type strains. These data suggest that the genes required for maintenance of ER integrity are important for the formation of disomic chromosomes in C. neoformans under azole stress.
C1 [Ngamskulrungroj, Popchai; Chang, Yun; Kwon-Chung, Kyung J.] NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
   [Ngamskulrungroj, Popchai] Mahidol Univ, Dept Microbiol, Fac Med, Siriraj Hosp, Bangkok 10700, Thailand.
   [Hansen, Bryan; Fischer, Elizabeth] NIAID, Electron Microscopy Unit, Rocky Mt Labs, NIH, Hamilton, MT USA.
   [Bugge, Cliff] FEI Co, Hillsboro, OR USA.
RP Ngamskulrungroj, P (reprint author), NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM june_kwon-chung@nih.gov
FU Division of Intramural Research, National Institute of Allergy and
   Infectious Diseases, National Institutes of Health
FX This study was primarily supported by funds from the Division of
   Intramural Research, National Institute of Allergy and Infectious
   Diseases, National Institutes of Health. The funders had no role in
   study design, data collection and analysis, decision to publish, or
   preparation of the manuscript. No additional external funding was
   received for this study.
NR 62
TC 11
Z9 11
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 MAR 7
PY 2012
VL 7
IS 3
AR e33022
DI 10.1371/journal.pone.0033022
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 929KK
UT WOS:000303060800078
PM 22412978
ER

PT J
AU Thu, KL
   Vucic, EA
   Chari, R
   Zhang, W
   Lockwood, WW
   English, JC
   Fu, R
   Wang, P
   Feng, ZD
   MacAulay, CE
   Gazdar, AF
   Lam, S
   Lam, WL
AF Thu, Kelsie L.
   Vucic, Emily A.
   Chari, Raj
   Zhang, Wei
   Lockwood, William W.
   English, John C.
   Fu, Rong
   Wang, Pei
   Feng, Ziding
   MacAulay, Calum E.
   Gazdar, Adi F.
   Lam, Stephen
   Lam, Wan L.
TI Lung Adenocarcinoma of Never Smokers and Smokers Harbor Differential
   Regions of Genetic Alteration and Exhibit Different Levels of Genomic
   Instability
SO PLOS ONE
LA English
DT Article
ID SMALL-CELL; CHROMOSOMAL-ABERRATIONS; CANCER GENOME; COPY NUMBER; ARRAY
   CGH; NONSMOKERS; MUTATIONS; SIGNATURES; RESOLUTION; IMBALANCE
AB Recent evidence suggests that the observed clinical distinctions between lung tumors in smokers and never smokers (NS) extend beyond specific gene mutations, such as EGFR, EML4-ALK, and KRAS, some of which have been translated into targeted therapies. However, the molecular alterations identified thus far cannot explain all of the clinical and biological disparities observed in lung tumors of NS and smokers. To this end, we performed an unbiased genome-wide, comparative study to identify novel genomic aberrations that differ between smokers and NS. High resolution whole genome DNA copy number profiling of 69 lung adenocarcinomas from smokers (n = 39) and NS (n = 30) revealed both global and regional disparities in the tumor genomes of these two groups. We found that NS lung tumors had a greater proportion of their genomes altered than those of smokers. Moreover, copy number gains on chromosomes 5q, 7p, and 16p occurred more frequently in NS. We validated our findings in two independently generated public datasets. Our findings provide a novel line of evidence distinguishing genetic differences between smoker and NS lung tumors, namely, that the extent of segmental genomic alterations is greater in NS tumors. Collectively, our findings provide evidence that these lung tumors are globally and genetically different, which implies they are likely driven by distinct molecular mechanisms.
C1 [Thu, Kelsie L.; Vucic, Emily A.; Chari, Raj; Lockwood, William W.; MacAulay, Calum E.; Lam, Stephen; Lam, Wan L.] British Columbia Canc Res Ctr, Dept Integrat Oncol, Vancouver, BC V5Z 1L3, Canada.
   [Chari, Raj] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
   [Zhang, Wei; 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.
   [English, John C.] Vancouver Gen Hosp, Dept Pathol, Vancouver, BC V5Z 1M9, Canada.
   [Fu, Rong; Wang, Pei; Feng, Ziding] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
RP Thu, KL (reprint author), British Columbia Canc Res Ctr, Dept Integrat Oncol, Vancouver, BC V5Z 1L3, Canada.
EM kthu@bccrc.ca
RI MacAulay, Calum/K-1795-2016; 
OI Vucic, Emily/0000-0002-2728-8708
FU Canadian Institutes for Health Research (CIHR) [MOP 86731, MOP 94867];
   Canadian Cancer Society [CCS20485]; NCI Early Detection Research
   Network; Canary Foundation; Frederick Banting Canada Graduate
   Scholarship; Charles Best Canada Graduate Scholarship; Vanier Canada
   Graduate Scholarship; Banting Postdoctoral fellowship
FX Funding provided by the Canadian Institutes for Health Research (CIHR;
   MOP 86731, MOP 94867), Canadian Cancer Society (CCS20485), NCI Early
   Detection Research Network, Canary Foundation, Frederick Banting and
   Charles Best Canada Graduate Scholarships [KLT, EAV and RC], Vanier
   Canada Graduate Scholarship [KLT], Banting Postdoctoral fellowship [RC],
   and CIHR Jean Francois St-Denis Fellowship in Cancer Research [WWL]. The
   funders had no role in study design, data collection and analysis,
   decision to publish, or preparation of the manuscript.
NR 29
TC 23
Z9 26
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 MAR 7
PY 2012
VL 7
IS 3
AR e33003
DI 10.1371/journal.pone.0033003
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 929KK
UT WOS:000303060800073
PM 22412972
ER

PT J
AU Ashrafian, H
   Czibik, G
   Bellahcene, M
   Aksentijevic, D
   Smith, AC
   Mitchell, SJ
   Dodd, MS
   Kirwan, J
   Byrne, JJ
   Ludwig, C
   Isackson, H
   Yavari, A
   Stottrup, NB
   Contractor, H
   Cahill, TJ
   Sahgal, N
   Ball, DR
   Birkler, RID
   Hargreaves, L
   Tennant, DA
   Land, J
   Lygate, CA
   Johannsen, M
   Kharbanda, RK
   Neubauer, S
   Redwood, C
   de Cabo, R
   Ahmet, I
   Talan, M
   Gunther, UL
   Robinson, AJ
   Viant, MR
   Pollard, PJ
   Tyler, DJ
   Watkins, H
AF Ashrafian, Houman
   Czibik, Gabor
   Bellahcene, Mohamed
   Aksentijevic, Dunja
   Smith, Anthony C.
   Mitchell, Sarah J.
   Dodd, Michael S.
   Kirwan, Jennifer
   Byrne, Jonathan J.
   Ludwig, Christian
   Isackson, Henrik
   Yavari, Arash
   Stottrup, Nicolaj B.
   Contractor, Hussain
   Cahill, Thomas J.
   Sahgal, Natasha
   Ball, Daniel R.
   Birkler, Rune I. D.
   Hargreaves, Lain
   Tennant, Daniel A.
   Land, John
   Lygate, Craig A.
   Johannsen, Mogens
   Kharbanda, Rajesh K.
   Neubauer, Stefan
   Redwood, Charles
   de Cabo, Rafael
   Ahmet, Ismayil
   Talan, Mark
   Guenther, Ulrich L.
   Robinson, Alan J.
   Viant, Mark R.
   Pollard, Patrick J.
   Tyler, Damian J.
   Watkins, Hugh
TI Fumarate Is Cardioprotective via Activation of the Nrf2 Antioxidant
   Pathway
SO CELL METABOLISM
LA English
DT Article
ID TRICARBOXYLIC-ACID-CYCLE; C-13 MAGNETIC-RESONANCE; IN-VIVO ASSESSMENT;
   HEME OXYGENASE-1; RAT-HEART; KEAP1-NRF2 PATHWAY; STRESS-RESPONSE;
   MYOCARDIAL-ISCHEMIA; REPERFUSION INJURY; EXPRESSION
AB The citric acid cycle (CAC) metabolite fumarate has been proposed to be cardioprotective; however, its mechanisms of action remain to be determined. To augment cardiac fumarate levels and to assess fumarate's cardioprotective properties, we generated fumarate hydratase (Fh1) cardiac knockout (KO) mice. These fumarate-replete hearts were robustly protected from ischemia-reperfusion injury (I/R). To compensate for the loss of Fh1 activity, KO hearts maintain ATP levels in part by channeling amino acids into the CAC. In addition, by stabilizing the transcriptional regulator Nrf2, Fh1 KO hearts upregulate protective antioxidant response element genes. Supporting the importance of the latter mechanism, clinically relevant doses of dimethylfumarate upregulated Nrf2 and its target genes, hence protecting control hearts, but failed to similarly protect Nrf2-KO hearts in an in vivo model of myocardial infarction. We propose that clinically established fumarate derivatives activate the Nrf2 pathway and are readily testable cytoprotective agents.
C1 [Ashrafian, Houman; Czibik, Gabor; Bellahcene, Mohamed; Aksentijevic, Dunja; Isackson, Henrik; Yavari, Arash; Contractor, Hussain; Cahill, Thomas J.; Lygate, Craig A.; Kharbanda, Rajesh K.; Neubauer, Stefan; Redwood, Charles; Watkins, Hugh] Univ Oxford, Dept Cardiovasc Med, Oxford OX3 9DU, England.
   [Smith, Anthony C.; Robinson, Alan J.] Med Res Council Mitochondrial Biol Unit, Cambridge CB2 0XY, England.
   [Mitchell, Sarah J.] Univ Sydney, Royal N Shore Hosp, Kolling Inst Med Res, St Leonards, NSW 2065, Australia.
   [Mitchell, Sarah J.; de Cabo, Rafael] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA.
   [Ahmet, Ismayil; Talan, Mark] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA.
   [Dodd, Michael S.; Ball, Daniel R.; Tyler, Damian J.] Univ Oxford, Dept Physiol Anat & Genet, Cardiac Metab Res Grp, Oxford OX1 3QX, England.
   [Kirwan, Jennifer; Byrne, Jonathan J.; Viant, Mark R.] Univ Birmingham, Sch Biosci, Birmingham B15 2TT, W Midlands, England.
   [Ludwig, Christian; Tennant, Daniel A.; Guenther, Ulrich L.] Univ Birmingham, Sch Canc Sci, Birmingham B15 2TT, W Midlands, England.
   [Stottrup, Nicolaj B.; Birkler, Rune I. D.; Johannsen, Mogens] Aarhus Univ Hosp, Skejby Hosp, Dept Cardiol, Aarhus 8200 N, Denmark.
   [Stottrup, Nicolaj B.; Birkler, Rune I. D.; Johannsen, Mogens] Aarhus Univ Hosp, Sect Toxicol & Drug Anal, Dept Forens Med, Aarhus 8200 N, Denmark.
   [Hargreaves, Lain; Land, John; Pollard, Patrick J.] Natl Hosp Neurol, Neurometabol Unit, London WC1N 3BG, England.
   [Sahgal, Natasha; Watkins, Hugh] Univ Oxford, Nuffield Dept Med, Oxford OX3 7BN, England.
RP Ashrafian, H (reprint author), Univ Oxford, Dept Cardiovasc Med, Oxford OX3 9DU, England.
EM houman.ashrafian@cardiov.ox.ac.uk
RI Pollard, Patrick/F-7516-2012; Ludwig, Christian/E-7679-2011; Johannsen,
   Mogens/E-5374-2011; Viant, Mark/B-6339-2009; de Cabo,
   Rafael/J-5230-2016; 
OI Kirwan, Jennifer/0000-0002-5423-1651; , rafael/0000-0003-2830-5693;
   Smith, Anthony/0000-0003-0141-0434; Watkins, Hugh/0000-0002-5287-9016;
   Tennant, Daniel/0000-0003-0499-2732; Kharbanda,
   Rajesh/0000-0002-5356-2395; Lygate, Craig/0000-0001-6079-0284; Pollard,
   Patrick/0000-0002-4459-4993; Ludwig, Christian/0000-0001-8901-6970;
   Tyler, Damian/0000-0002-0780-8905; Dodd, Michael/0000-0002-1217-4660;
   Johannsen, Mogens/0000-0002-2548-7025; Viant, Mark/0000-0001-5898-4119;
   de Cabo, Rafael/0000-0002-3354-2442; Yavari, Arash/0000-0002-0815-5088;
   Ashrafian, Houman/0000-0003-3988-378X
FU Oxford British Heart Foundation Centre of Research Excellence; British
   Heart Foundation (BHF) [RG/02/010, RG/05/005]; Medical Research Council,
   UK; Medical Research Council; Oxford Instruments Molecular Biotools; GE
   Healthcare; Wellcome Trust [075491/Z/04]; Fondation Leducq [06CVD];
   Lundbeck Foundation; National Health and Medical Research Council of
   Australia [1016439]; National Institute on Aging of the National
   Institutes of Health, USA; Beit Memorial Fellowship
FX H.A. and H.W. are supported by the Oxford British Heart Foundation
   Centre of Research Excellence Award, and the the British Heart
   Foundation (BHF Grant RG/02/010). A.J.R. and A.C.S. are supported by the
   Medical Research Council, UK. D.A. and S.N. are supported by the British
   Heart Foundation Programme Grant RG/05/005. M.S.D., D.R.B., and D.J.T.
   are supported by research grants from the British Heart Foundation, the
   Medical Research Council, Oxford Instruments Molecular Biotools, and GE
   Healthcare. N.S.'s work is supported by the Core Award Grant 075491/Z/04
   from the Wellcome Trust. N.B.S. is supported by the Fondation Leducq
   (06CVD) and the Lundbeck Foundation. P.J.P. is in receipt of a Beit
   Memorial Fellowship. S.J.M. is supported by a National Health and
   Medical Research Council of Australia CJ Martin Early Career Fellowship
   (1016439). The Thermo Scientific LTQ FT Ultra and Bruker NMR
   spectrometers used here were obtained through the Birmingham Science
   City Translational Medicine project, with support from Advantage West
   Midlands; the NMR spectrometer was further supported by the Wolfson
   Foundation. This study was also funded in part by the Intramural
   Research Program of the National Institute on Aging of the National
   Institutes of Health, USA. We gratefully acknowledge and thank Dr. Reza
   Morovat, consultant clinical biochemist at the Oxford Radcliffe NHS
   Trust, Oxford; and Dawn Phillips-Boyer and Dawn Nines for their
   excellent animal care and assistance.
NR 65
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U1 0
U2 18
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
J9 CELL METAB
JI Cell Metab.
PD MAR 7
PY 2012
VL 15
IS 3
BP 361
EP 371
DI 10.1016/j.cmet.2012.01.017
PG 11
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 911EZ
UT WOS:000301701400016
PM 22405071
ER

PT J
AU Xue, L
   McNeil, BD
   Wu, XS
   Luo, FJ
   He, LM
   Wu, LG
AF Xue, Lei
   McNeil, Benjamin D.
   Wu, Xin-Sheng
   Luo, Fujun
   He, Liming
   Wu, Ling-Gang
TI A Membrane Pool Retrieved via Endocytosis Overshoot at Nerve Terminals:
   A Study of Its Retrieval Mechanism and Role
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID SYNAPTIC VESICLE ENDOCYTOSIS; SLOW ENDOCYTOSIS; HIPPOCAMPAL SYNAPSES;
   CNS SYNAPSE; CALCIUM; EXOCYTOSIS; CALCINEURIN; DYNAMIN; CA2+; PITUITARY
AB Endocytosis overshoot, which retrieves more membrane than vesicles just being exocytosed, occurs at nerve terminals and non-neuronal secretory cells. The mechanism that retrieves the overshoot membrane pool and the role of this pool remain largely unknown. We addressed this issue at the rat calyx of Held nerve terminal with capacitance measurements. We found that every calyx contained an overshoot pool similar to 1.8 times the readily releasable pool. Retrieval of this pool required large calcium influx, and was inhibited by blockers of calcium/calmodulin-activated calcineurin and dynamin, suggesting the involvement of calcineurin and dynamin in endocytosis overshoot. Depletion of the overshoot pool slowed down compensatory endocytosis, whereas recovery of the overshoot pool via exocytosis that deposited stranded vesicles to the plasma membrane led to recovery of compensatory endocytosis, suggesting that the overshoot pool enhances endocytosis efficiency. These results suggest that the overshoot pool exists at every nerve terminal, is of limited size arising from vesicles stranded at the plasma membrane, is retrieved via calcium/calmodulin/calcineurin and dynamin signaling pathway, and can enhance endocytosis efficiency. Potential mechanisms for how the endocytosis overshoot pool enhances endocytosis efficiency are discussed.
C1 [Xue, Lei; McNeil, Benjamin D.; Wu, Xin-Sheng; Luo, Fujun; He, Liming; Wu, Ling-Gang] NINDS, Bethesda, MD 20892 USA.
RP Wu, LG (reprint author), NINDS, 35 Convent Dr,Bldg 35,Rm 2B-1012, Bethesda, MD 20892 USA.
EM wul@ninds.nih.gov
RI Luo, Fujun/I-1016-2013
FU National Institute of Neurological Disorders and Stroke
FX This work was supported by the National Institute of Neurological
   Disorders and Stroke Intramural Research Program.
NR 26
TC 9
Z9 9
U1 0
U2 4
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 MAR 7
PY 2012
VL 32
IS 10
BP 3398
EP 3404
DI 10.1523/JNEUROSCI.5943-11.2012
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 905SV
UT WOS:000301295300015
PM 22399762
ER

PT J
AU Tokar, EJ
   Diwan, BA
   Waalkes, MP
AF Tokar, Erik J.
   Diwan, Bhalchandra A.
   Waalkes, Michael P.
TI Renal, hepatic, pulmonary and adrenal tumors induced by prenatal
   inorganic arsenic followed by dimethylarsinic acid in adulthood in CD1
   mice
SO TOXICOLOGY LETTERS
LA English
DT Article
DE Arsenic; Mouse; Cancer; Kidney; Liver; Early; life; Lung; DMA
ID EXPOSURE IN-UTERO; MALE F344 RATS; URINARY-BLADDER; POSTNATAL
   DIETHYLSTILBESTROL; CANCER-MORTALITY; DRINKING-WATER; CARCINOGENICITY;
   INDUCTION; LIVER; METABOLISM
AB Inorganic arsenic, an early life carcinogen in humans and mice, can initiate lesions promotable by other agents in later life. The biomethylation product of arsenic, dimethylarsinic acid (DMA), is a multi-site tumor promoter. Thus, pregnant CD1 mice were given drinking water (0 ppm or 85 ppm arsenic) from gestation day 8 to 18 and after weaning male offspring received DMA (0 ppm or 200 ppm; drinking water) for up to 2 years. No renal tumors occurred in controls or DMA alone treated mice while gestational arsenic exposure plus later DMA induced a significant renal tumor incidence of 17% (primarily renal cell carcinoma). Arsenic plus DMA or arsenic alone also increased renal hyperplasia over control but DMA alone did not. Arsenic alone, DMA alone and arsenic plus DMA all induced urinary bladder hyperplasia (33-35%) versus control (2%). Compared to control (6%), arsenic alone tripled hepatocellular carcinoma (20%), and arsenic plus DMA doubled this rate again (43%), but DMA alone had no effect. DMA alone, arsenic alone, and arsenic plus DMA increased lung adenocarcinomas and adrenal adenomas versus control. Overall, DMA in adulthood promoted tumors/lesions initiated by prenatal arsenic in the kidney and liver, but acted independently in the urinary bladder, lung and adrenal. Published by Elsevier Ireland Ltd.
C1 [Tokar, Erik J.; Waalkes, Michael P.] NIEHS, Inorgan Toxicol Grp, Natl Toxicol Program, Branch Lab, Res Triangle Pk, NC 27709 USA.
   [Diwan, Bhalchandra A.] NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21701 USA.
RP Waalkes, MP (reprint author), NIEHS, Inorgan Toxicol Grp, Natl Toxicol Program, Branch Lab, 111 Alexander Dr,POB 12233,MD E0-07, Res Triangle Pk, NC 27709 USA.
EM waalkes@niehs.nih.gov
FU NIEHS; NIH, National Cancer Institute, Center for Cancer Research;
   National Cancer Institute, National Institutes of Health
   [HHSN261200800001E]
FX The authors wish to thank Drs. Bucher, Walker, Morgan and Person for
   critical evaluation of this manuscript and Dan Logsdon for expert
   technical assistance. This research was supported in part by the
   National Toxicology Program, NIEHS and by the Intramural Research
   program of the NIH, National Cancer Institute, Center for Cancer
   Research. This article may be the work product of an employee or group
   of employees of the NIEHS, National Institutes of Health (NIH), however,
   the statements contained herein do not necessarily represent the
   statements, opinions or conclusions of the NIEHS, NIH or the United
   States Government. This project was also supported in part with federal
   funds from the National Cancer Institute, National Institutes of Health,
   under contract HHSN261200800001E. The content of this publication does
   not necessarily reflect the views or the 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 30
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U1 0
U2 7
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 MAR 7
PY 2012
VL 209
IS 2
BP 179
EP 185
DI 10.1016/j.toxlet.2011.12.016
PG 7
WC Toxicology
SC Toxicology
GA 905MV
UT WOS:000301277200011
PM 22230260
ER

PT J
AU Engel, J
   McDermott, MP
   Wiebe, S
   Langfitt, JT
   Stern, JM
   Dewar, S
   Sperling, MR
   Gardiner, I
   Erba, G
   Fried, I
   Jacobs, M
   Vinters, HV
   Mintzer, S
   Kieburtz, K
AF Engel, Jerome, Jr.
   McDermott, Michael P.
   Wiebe, Samuel
   Langfitt, John T.
   Stern, John M.
   Dewar, Sandra
   Sperling, Michael R.
   Gardiner, Irenita
   Erba, Giuseppe
   Fried, Itzhak
   Jacobs, Margaret
   Vinters, Harry V.
   Mintzer, Scott
   Kieburtz, Karl
CA Early Randomized Surgical Epilepsy
TI Early Surgical Therapy for Drug-Resistant Temporal Lobe Epilepsy A
   Randomized Trial
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID QUALITY-OF-LIFE; INTRACTABLE EPILEPSY; SURGERY; MULTICENTER; INVENTORY;
   LOBECTOMY; DIAGNOSIS; SEIZURES; OUTCOMES; LONG
AB Context Despite reported success, surgery for pharmacoresistant seizures is often seen as a last resort. Patients are typically referred for surgery after 20 years of seizures, often too late to avoid significant disability and premature death.
   Objective We sought to determine whether surgery soon after failure of 2 antiepileptic drug (AED) trials is superior to continued medical management in controlling seizures and improving quality of life (QOL).
   Design, Setting, and Participants The Early Randomized Surgical Epilepsy Trial (ERSET) is a multicenter, controlled, parallel-group clinical trial performed at 16 US epilepsy surgery centers. The 38 participants (18 men and 20 women; aged >= 12 years) had mesial temporal lobe epilepsy (MTLE) and disabling seizues for no more than 2 consecutive years following adequate trials of 2 brand-name AEDs. Eligibility for anteromesial temporal resection (AMTR) was based on a standardized presurgical evaluation protocol. Participants were randomized to continued AED treatment or AMTR 2003-2007, and observed for 2 years. Planned enrollment was 200, but the trial was halted prematurely due to slow accrual.
   Intervention Receipt of continued AED treatment (n=23) or a standardized AMTR plus AED treatment (n=15). In the medical group, 7 participants underwent AMTR prior to the end of follow-up and 1 participant in the surgical group never received surgery.
   Main Outcome Measures The primary outcome variable was freedom from disabling seizures during year 2 of follow-up. Secondary outcome variables were health-related QOL (measured primarily by the 2-year change in the Quality of Life in Epilepsy 89 [QOLIE-89] overall T-score), cognitive function, and social adaptation.
   Results Zero of 23 participants in the medical group and 11 of 15 in the surgical group were seizure free during year 2 of follow-up (odds ratio=infinity; 95% CI, 11.8 to infinity; P<.001). In an intention-to-treat analysis, the mean improvement in QOLIE-89 overall T-score was higher in the surgical group than in the medical group but this difference was not statistically significant (12.6 vs 4.0 points; treatment effect=8.5; 95% CI, -1.0 to 18.1; P=.08). When data obtained after surgery from participants in the medical group were excluded, the effect of surgery on QOL was significant (12.8 vs 2.8 points; treatment effect=9.9; 95% CI, 2.2 to 17.7; P=.01). Memory decline (assessed using the Rey Auditory Verbal Learning Test) occurred in 4 participants (36%) after surgery, consistent with rates seen in the literature; but the sample was too small to permit definitive conclusions about treatment group differences in cognitive outcomes. Adverse events included a transient neurologic deficit attributed to a magnetic resonance imaging-identified postoperative stroke in a participant who had surgery and 3 cases of status epilepticus in the medical group.
   Conclusions Among patients with newly intractable disabling MTLE, resective surgery plus AED treatment resulted in a lower probability of seizures during year 2 of follow-up than continued AED treatment alone. Given the premature termination of the trial, the results should be interpreted with appropriate caution.
C1 [Engel, Jerome, Jr.; Stern, John M.; Dewar, Sandra] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA.
   [McDermott, Michael P.] Univ Rochester, Dept Biostat & Computat Biol, Rochester, NY USA.
   [Wiebe, Samuel] Univ Calgary, Calgary, AB, Canada.
   [Wiebe, Samuel] Foothills Med Ctr, Div Neurol, Calgary, AB, Canada.
   [Langfitt, John T.; Erba, Giuseppe] Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14642 USA.
   [Gardiner, Irenita; Kieburtz, Karl] Univ Rochester, Med Ctr, Ctr Human Expt Therapeut, Rochester, NY 14642 USA.
   [Fried, Itzhak; Mintzer, Scott] Thomas Jefferson Univ, Dept Neurol, Philadelphia, PA 19107 USA.
   [Sperling, Michael R.; Mintzer, Scott] Thomas Jefferson Univ, Jefferson Comprehens Epilepsy Ctr, Philadelphia, PA 19107 USA.
   [Fried, Itzhak] Ronald Reagan UCLA Med Ctr, Dept Neurosurg, Los Angeles, CA USA.
   [Vinters, Harry V.] Ronald Reagan UCLA Med Ctr, Dept Anat & Clin Pathol, Los Angeles, CA USA.
   [Jacobs, Margaret] Amer Epilepsy Soc, Hartford, CT USA.
   [Jacobs, Margaret] Natl Inst Neurol Disorders & Stroke, NIH, Rockville, MD USA.
RP Engel, J (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, 710 Westwood Plaza, Los Angeles, CA 90095 USA.
EM engel@ucla.edu
RI French, Jacqueline/G-6795-2013; Lopez Rodriguez, Fernando/A-7557-2016
OI French, Jacqueline/0000-0003-2242-8027; Lopez Rodriguez,
   Fernando/0000-0002-0519-9624
FU National Institutes of Health (NIH); National Institute of Neurological
   Disorders and Stroke (NINDS); Medtronics; Valeant; Acorda; US Food and
   Drug Administration; Esai; Johnson Johnson; Novartis; Lippincott
   [WO2009/123734A1, WO2009/123735A1]; UCB Pharmaceuticals; Teva
   Pharmaceutical Industries; Smith and Nephew; Synosia; Impax
   Pharmaceuticals; Medivation; NeuroSearch Sweden AB;
   Boehringer-Ingelheim; Pfizer; Canadian Institutes of Health Research;
   International League Against Epilepsy; UCSF/Elekta; Northern Illinois
   University; University of Cincinnatti; NIH CSR (Center for Scientific
   Review); NINDS; Agency for Healthcare Research and Quality; UCB; Vertex;
   Sunovion; Eisai; Neuropace; SK Life Sciences; Neuronex; Epilepsia;
   National Institutes of Health [R21 NS37897, U01 NS42372]
FX All authors have completed and submitted the ICMJE Form for Disclosure
   of Potential Conflicts of Interest. Drs Engel, Stern, Sperling, and
   Mintzer and Mss Gardiner and Jacobs report receipt of an institutional
   grant from the National Institutes of Health (NIH); and Drs McDermott,
   Langfitt, and Fried report receipt of an institutional grant from the
   National Institute of Neurological Disorders and Stroke (NINDS). Dr
   Engel reports receipt of consultancy fees from Medtronics, Valeant,
   Acorda, the US Food and Drug Administration, Best Doctors; receipt of
   fees to the institution for expert testimony; receipt of
   lecture/speakers bureau fees from Esai, Johnson & Johnson, Novartis,
   Lippincott; receipt of patent fees (WO2009/123734A1 and
   WO2009/123735A1); receipt of royalties from Wolters Kluwer, Wiley
   Blackwell, Elsevier, MedLink; and receipt of fees for travel
   accommodations/meeting expenses from UCB Pharmaceuticals. Dr McDermott
   reports receipt of fees to the institution for travel
   accommodations/meeting expenses for this study from NINDS, fees to the
   institution for consultancy from BoehringerIngelheim and Pfizer; receipt
   of consultancy fees from Teva Pharmaceutical Industries, Smith and
   Nephew, Synosia, Impax Pharmaceuticals; grant support or pending grant
   support to the institution from Medivation, NeuroSearch Sweden AB,
   Boehringer-Ingelheim, Pfizer. Dr Wiebe reports grant support from NINDS,
   fees for travel accommodations/meeting expenses from NINDS; employment
   with the University of Calgary; grant support or pending grant support
   from the Canadian Institutes of Health Research; fees for travel
   accommodations/meeting expenses from the International League Against
   Epilepsy. Dr Langfitt reports receipt of fees for travel
   accommodations/meeting expenses from NIH; consultancy fees from NINDS,
   UCSF/Elekta, Northern Illinois University, University of Cincinnatti,
   NIH CSR (Center for Scientific Review); grant support or pending grant
   support from NINDS and the Agency for Healthcare Research and Quality;
   fees to the institution for development of educational presentations
   from NIH. Dr Stern reports receipt of fees for travel
   accommodations/meeting expenses from NIH. Dr Sperling reports receipt of
   consultancy fees from UCB, Vertex, Sunovion; grant support or pending
   grant support from NIH, UCP, Vertex, Eisai, Sunovion, Medtronics,
   Neuropace, SK Life Sciences, Novartis, Neuronex; lecture/speakers bureau
   fees from UCB; other fees as associate editor from Epilepsia. Mss
   Gardiner and Dewar and Dr Erba report no disclosures.; This study was
   supported by the National Institutes of Health (grant numbers R21
   NS37897 and U01 NS42372).
NR 44
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U1 4
U2 40
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 MAR 7
PY 2012
VL 307
IS 9
BP 922
EP 930
DI 10.1001/jama.2012.220
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 904CU
UT WOS:000301172100020
PM 22396514
ER

PT J
AU Lee, C
   Raffaghello, L
   Brandhorst, S
   Safdie, FM
   Bianchi, G
   Martin-Montalvo, A
   Pistoia, V
   Wei, M
   Hwang, S
   Merlino, A
   Emionite, L
   de Cabo, R
   Longo, VD
AF Lee, Changhan
   Raffaghello, Lizzia
   Brandhorst, Sebastian
   Safdie, Fernando M.
   Bianchi, Giovanna
   Martin-Montalvo, Alejandro
   Pistoia, Vito
   Wei, Min
   Hwang, Saewon
   Merlino, Annalisa
   Emionite, Laura
   de Cabo, Rafael
   Longo, Valter D.
TI Fasting Cycles Retard Growth of Tumors and Sensitize a Range of Cancer
   Cell Types to Chemotherapy
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID GENE SET ENRICHMENT; DIETARY RESTRICTION; LIFE-SPAN; CALORIC
   RESTRICTION; STRESS RESISTANCE; HUMANS; MODEL; YEAST; ACTIVATION;
   MECHANISMS
AB Short-term starvation (or fasting) protects normal cells, mice, and potentially humans from the harmful side effects of a variety of chemotherapy drugs. Here, we show that treatment with starvation conditions sensitized yeast cells (Saccharomyces cerevisiae) expressing the oncogene-like RAS2(val19) to oxidative stress and 15 of 17 mammalian cancer cell lines to chemotherapeutic agents. Cycles of starvation were as effective as chemotherapeutic agents in delaying progression of different tumors and increased the effectiveness of these drugs against melanoma, glioma, and breast cancer cells. In mouse models of neuroblastoma, fasting cycles plus chemotherapy drugs-but not either treatment alone-resulted in long-term cancer-free survival. In 4T1 breast cancer cells, short-term starvation resulted in increased phosphorylation of the stress-sensitizing Akt and S6 kinases, increased oxidative stress, caspase-3 cleavage, DNA damage, and apoptosis. These studies suggest that multiple cycles of fasting promote differential stress sensitization in a wide range of tumors and could potentially replace or augment the efficacy of certain chemotherapy drugs in the treatment of various cancers.
C1 [Lee, Changhan; Brandhorst, Sebastian; Safdie, Fernando M.; Wei, Min; Hwang, Saewon; Merlino, Annalisa; Longo, Valter D.] Univ So Calif, Dept Biol Sci, Andrus Gerontol Ctr, Los Angeles, CA 90089 USA.
   [Lee, Changhan; Brandhorst, Sebastian; Safdie, Fernando M.; Wei, Min; Hwang, Saewon; Merlino, Annalisa; Longo, Valter D.] Univ So Calif, Norris Canc Ctr, Los Angeles, CA 90089 USA.
   [Raffaghello, Lizzia; Bianchi, Giovanna; Pistoia, Vito] Giannina Gaslini Inst, Lab Oncol, I-16145 Genoa, Italy.
   [Brandhorst, Sebastian] Univ Duisburg Essen, Fac Biol, Ctr Med Biotechnol, D-45117 Essen, Germany.
   [Martin-Montalvo, Alejandro; de Cabo, Rafael] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA.
   [Emionite, Laura] Anim Res Facil Ist Tumori, I-16145 Genoa, Italy.
RP Longo, VD (reprint author), Univ So Calif, Dept Biol Sci, Andrus Gerontol Ctr, 3715 McClintock Ave, Los Angeles, CA 90089 USA.
EM vlongo@usc.edu
RI perumal, murugiah/D-1565-2012; de Cabo, Rafael/J-5230-2016;
   Martin-Montalvo, Alejandro/C-2031-2017; 
OI Wei, Min/0000-0002-2649-9271; de Cabo, Rafael/0000-0002-3354-2442;
   Martin-Montalvo, Alejandro/0000-0002-3886-5355; Raffaghello,
   Lizzia/0000-0003-2357-0607; , rafael/0000-0003-2830-5693
FU NIH/National Institute on Aging [AG20642, AG025135, P01 AG034906]; Ted
   Bakewell (The Bakewell Foundation); V Foundation for Cancer Research;
   USC Norris Cancer Center; My First Associazione Italiana per la Ricerca
   sul Cancro; Fondazione Italiana Ricerca sul Cancro
FX This study was funded in part by NIH/National Institute on Aging grants
   AG20642, AG025135, and P01 AG034906; Ted Bakewell (The Bakewell
   Foundation); the V Foundation for Cancer Research; and a USC Norris
   Cancer Center pilot grant to V.D.L. L.R. is a recipient of a My First
   Associazione Italiana per la Ricerca sul Cancro grant, and G.B. is a
   recipient of a Fondazione Italiana Ricerca sul Cancro fellowship.
NR 34
TC 68
Z9 70
U1 4
U2 33
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 MAR 7
PY 2012
VL 4
IS 124
AR 124ra27
DI 10.1126/scitranslmed.3003293
PG 10
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 905UY
UT WOS:000301302600003
PM 22323820
ER

PT J
AU Wayson, M
   Lee, C
   Sgouros, G
   Treves, ST
   Frey, E
   Bolch, WE
AF Wayson, Michael
   Lee, Choonsik
   Sgouros, George
   Treves, S. Ted
   Frey, Eric
   Bolch, Wesley E.
TI Internal photon and electron dosimetry of the newborn patient-a hybrid
   computational phantom study
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
ID ICRP REFERENCE NEWBORN; REFERENCE ADULT MALE; DOSE ASSESSMENT;
   NUCLEAR-MEDICINE; 1ST YEAR; MODELS; FAMILY; CHILDREN; MIRD; LIFE
AB Estimates of radiation absorbed dose to organs of the nuclear medicine patient are a requirement for administered activity optimization and for stochastic risk assessment. Pediatric patients, and in particular the newborn child, represent that portion of the patient population where such optimization studies are most crucial owing to the enhanced tissue radiosensitivities and longer life expectancies of this patient subpopulation. In cases where whole-body CT imaging is not available, phantom-based calculations of radionuclide S values-absorbed dose to a target tissue per nuclear transformation in a source tissue-are required for dose and risk evaluation. In this study, a comprehensive model of electron and photon dosimetry of the reference newborn child is presented based on a high-resolution hybrid-voxel phantom from the University of Florida (UF) patient model series. Values of photon specific absorbed fraction (SAF) were assembled for both the reference male and female newborn using the radiation transport code MCNPX v2.6. Values of electron SAF were assembled in a unique and time-efficient manner whereby the collisional and radiative components of organ dose-for both self-and cross-dose terms-were computed separately. Dose to the newborn skeletal tissues were assessed via fluence-to-dose response functions reported for the first time in this study. Values of photon and electron SAFs were used to assemble a complete set of S values for some 16 radionuclides commonly associated with molecular imaging of the newborn. These values were then compared to those available in the OLINDA/EXM software. S value ratios for organ self-dose ranged from 0.46 to 1.42, while similar ratios for organ cross-dose varied from a low of 0.04 to a high of 3.49. These large discrepancies are due in large part to the simplistic organ modeling in the stylized newborn model used in the OLINDA/EXM software. A comprehensive model of internal dosimetry is presented in this study for the newborn nuclear medicine patient based upon the UF hybrid computational phantom. Photon dose response functions, photon and electron SAFs, and tables of radionuclide S values for the newborn child-both male and female-are given in a series of four electronic annexes available at stacks.iop.org/pmb/57/1433/mmedia. These values can be applied to optimization studies of image quality and stochastic risk for this most vulnerable class of pediatric patients.
C1 [Wayson, Michael; Bolch, Wesley E.] Univ Florida, J Crayton Pruitt Family Dept Biomed Engn, Gainesville, FL 32611 USA.
   [Lee, Choonsik] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Sgouros, George; Frey, Eric] Johns Hopkins Med Inst, Dept Radiol, Baltimore, MD 21287 USA.
   [Treves, S. Ted] Childrens Hosp, Div Nucl Med, Boston, MA 02115 USA.
RP Bolch, WE (reprint author), Univ Florida, J Crayton Pruitt Family Dept Biomed Engn, Gainesville, FL 32611 USA.
EM mikew13@ufl.edu; wbolch@ufl.edu
RI Lee, Choonsik/C-9023-2015
OI Lee, Choonsik/0000-0003-4289-9870
FU National Cancer Institute [R01 CA116743, R01 CA96441]; US Department of
   Energy [DE-FG07-06ID14773]
FX This research was supported in part by grants R01 CA116743 and R01
   CA96441 with the National Cancer Institute, and by grant
   DE-FG07-06ID14773 with the US Department of Energy.
NR 31
TC 7
Z9 7
U1 0
U2 6
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0031-9155
J9 PHYS MED BIOL
JI Phys. Med. Biol.
PD MAR 7
PY 2012
VL 57
IS 5
BP 1433
EP 1457
DI 10.1088/0031-9155/57/5/1433
PG 25
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 898XL
UT WOS:000300775600024
PM 22354044
ER

PT J
AU Billig, EMW
   O'Meara, WP
   Riley, EM
   McKenzie, FE
AF Billig, Erica M. W.
   O'Meara, Wendy P.
   Riley, Eleanor M.
   McKenzie, F. Ellis
TI Developmental allometry and paediatric malaria
SO MALARIA JOURNAL
LA English
DT Review
DE Malaria; Age-dependent; Allometry; Severe malarial anaemia; Cerebral
   malaria; Paediatric malaria
ID RED-BLOOD-CELL; PLASMODIUM-FALCIPARUM MALARIA; SPLENIC MARGINAL ZONE;
   AGE-RELATED-CHANGES; COMPLEMENT-REGULATORY PROTEINS; SUB-SAHARAN AFRICA;
   CEREBRAL MALARIA; TRANSMISSION INTENSITY; ANTIBODY-RESPONSES;
   HUMAN-ERYTHROCYTES
AB WHO estimates that 80% of mortality due to malaria occurs among infants and young children. Though it has long been established that malaria disproportionately affects children under age five, our understanding of the underlying biological mechanisms for this distribution remains incomplete. Many studies use age as an indicator of exposure, but age may affect malaria burden independently of previous exposure. Not only does the severity of malaria infection change with age, but the clinical manifestation of disease does as well: younger children are more likely to suffer severe anaemia, while older children are more likely to develop cerebral malaria. Intensity of transmission and acquired immunity are important determinants of this age variation, but age differences remain consistent over varying transmission levels. Thus, age differences in clinical presentation may involve inherent age-related factors as well as still-undiscovered facets of acquired immunity, perhaps including the rates at which relevant aspects of immunity are acquired. The concept of "allometry" - the relative growth of a part in relation to that of an entire organism or to a standard - has not previously been applied in the context of malaria infection. However, because malaria affects a number of organs and cells, including the liver, red blood cells, white blood cells, and spleen, which may intrinsically develop at rates partly independent of each other and of a child's overall size, developmental allometry may influence the course and consequences of malaria infection. Here, scattered items of evidence have been collected from a variety of disciplines, aiming to suggest possible research paths for investigating exposure-independent age differences affecting clinical outcomes of malaria infection.
C1 [Billig, Erica M. W.; McKenzie, F. Ellis] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
   [O'Meara, Wendy P.] Duke Univ, Sch Med, Durham, NC USA.
   [O'Meara, Wendy P.] Duke Global Hlth Inst, Durham, NC USA.
   [O'Meara, Wendy P.] Moi Univ, Eldoret, Kenya.
   [Riley, Eleanor M.] London Sch Hyg & Trop Med, Dept Infect & Trop Dis, London WC1E 7HT, England.
RP Billig, EMW (reprint author), NIH, Fogarty Int Ctr, Bldg 16, Bethesda, MD 20892 USA.
EM erica.billig@nih.gov
RI Riley, Eleanor/C-8960-2013
OI Riley, Eleanor/0000-0003-3447-3570
NR 132
TC 5
Z9 5
U1 1
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1475-2875
J9 MALARIA J
JI Malar. J.
PD MAR 6
PY 2012
VL 11
AR 64
DI 10.1186/1475-2875-11-64
PG 13
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 931HD
UT WOS:000303206100001
PM 22394452
ER

PT J
AU Lee, CW
   Bae, C
   Lee, J
   Ryu, JH
   Kim, HH
   Kohno, T
   Swartz, KJ
   Il Kim, J
AF Lee, Chul Won
   Bae, Chanhyung
   Lee, Jaeho
   Ryu, Jae Ha
   Kim, Ha Hyung
   Kohno, Toshiyuki
   Swartz, Kenton J.
   Il Kim, Jae
TI Solution Structure of Kurtoxin: A Gating Modifier Selective for Cav3
   Voltage-Gated Ca2+ Channels
SO BIOCHEMISTRY
LA English
DT Article
ID DEPENDENT K+ CHANNEL; ALPHA-LIKE TOXIN; NUCLEAR-MAGNETIC-RESONANCE;
   POTATO CARBOXYPEPTIDASE INHIBITOR; 3-DIMENSIONAL SOLUTION STRUCTURE;
   ANDROCTONUS-AUSTRALIS HECTOR; RELAXATION MATRIX ANALYSIS;
   BUTHUS-MARTENSII KARSCH; OMEGA-GRAMMOTOXIN-SIA; CALCIUM-CHANNELS
AB Kurtoxin is a 63-amino acid polypeptide isolated from the venom of the South African scorpion Parabuthus transvaalicus. It is the first and only peptide ligand known to interact with Cav3 (T-type) voltage-gated Ca2+ channels with high affinity and to modify the voltage-dependent gating of these channels. Here we describe the nuclear magnetic resonance (NMR) solution structure of kurtoxin determined using two- and three-dimensional NMR spectroscopy with dynamical simulated annealing calculations. The molecular structure of the toxin was highly similar to those of scorpion alpha-toxins and contained an alpha-helix, three beta-strands, and several turns stabilized by four disulfide bonds. This so-called "cysteine-stabilized alpha-helix and beta-sheet (CS alpha beta)" motif is found in a number of functionally varied small proteins. A detailed comparison of the backbone structure of kurtoxin with those of the scorpion a-toxins revealed that three regions [first long loop (Asp(8)-Ile(15)), beta-hairpin loop (Gly(39)-Leu(42)), and C-terminal segment (Arg(57)-Ala(63))] in kurtoxin significantly differ from the corresponding regions in scorpion alpha-toxins, suggesting that these regions may be important for interacting with Cav3 (T-type) Ca2+ channels. In addition, the surface profile of kurtoxin shows a larger and more focused electropositive patch along with a larger hydrophobic surface compared to those seen on scorpion alpha-toxins. These distinct surface properties of kurtoxin could explain its binding to Cav3 (T-type) voltage-gated Ca2+ channels.
C1 [Lee, Chul Won; Bae, Chanhyung; Lee, Jaeho; Ryu, Jae Ha; Il Kim, Jae] Gwangju Inst Sci & Technol GIST, Dept Life Sci, Kwangju 500712, South Korea.
   [Lee, Chul Won] Chonnam Natl Univ, Dept Chem, Kwangju 500757, South Korea.
   [Kim, Ha Hyung] Chung Ang Univ, Coll Pharm, Seoul 156756, South Korea.
   [Kohno, Toshiyuki] Kitasato Univ, Dept Biochem, Sch Med, Kanagawa 2520374, Japan.
   [Swartz, Kenton J.] NINDS, Mol Physiol & Biophys Sect, NIH, Bethesda, MD 20892 USA.
RP Il Kim, J (reprint author), Gwangju Inst Sci & Technol GIST, Dept Life Sci, Kwangju 500712, South Korea.
EM jikim@gist.ac.kr
FU Next-Generation BioGreen 21 Program [PJ008158]; Rural Development
   Administration, Republic of Korea; National Research Foundation of
   Korea; Korean Government (MEST) [NRF-C1ABA001-2011-0018559]; Brain
   Research Center [M103KV010005-06K2201-00610]; BioImaging Research Center
   at the Gwangju Institute of Science and Technology; Basic Research
   Projects in High-tech Industrial Technology; Gwangju Institute of
   Science and Technology
FX This research was supported by grants from the Next-Generation BioGreen
   21 Program (PJ008158); the Rural Development Administration, Republic of
   Korea; a National Research Foundation of Korea grant funded by the
   Korean Government (MEST) (NRF-C1ABA001-2011-0018559); the Brain Research
   Center of the 21st Century Frontier Research Program
   (M103KV010005-06K2201-00610); and the BioImaging Research Center at the
   Gwangju Institute of Science and Technology and Basic Research Projects
   in High-tech Industrial Technology funded by the Gwangju Institute of
   Science and Technology in 2011.
NR 112
TC 9
Z9 9
U1 0
U2 9
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD MAR 6
PY 2012
VL 51
IS 9
BP 1862
EP 1873
DI 10.1021/bi201633j
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 902EJ
UT WOS:000301021100006
PM 22329781
ER

PT J
AU Durrett, R
   Gleeson, JP
   Lloyd, AL
   Mucha, PJ
   Shi, F
   Sivakoff, D
   Socolar, JES
   Varghese, C
AF Durrett, Richard
   Gleeson, James P.
   Lloyd, Alun L.
   Mucha, Peter J.
   Shi, Feng
   Sivakoff, David
   Socolar, Joshua E. S.
   Varghese, Chris
TI Graph fission in an evolving voter model
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE coevolutionary network; quasi-stationary distribution; Wright-Fisher
   diffusion; approximate master equation
ID SOCIAL NETWORKS; SIR DYNAMICS; COEVOLUTION; SEGREGATION; EVOLUTION;
   SYSTEMS
AB We consider a simplified model of a social network in which individuals have one of two opinions (called 0 and 1) and their opinions and the network connections coevolve. Edges are picked at random. If the two connected individuals hold different opinions then, with probability 1 - alpha, one imitates the opinion of the other; otherwise (i.e., with probability alpha), the link between them is broken and one of them makes a new connection to an individual chosen at random (i) from those with the same opinion or (ii) from the network as a whole. The evolution of the system stops when there are no longer any discordant edges connecting individuals with different opinions. Letting rho be the fraction of voters holding the minority opinion after the evolution stops, we are interested in how rho depends on alpha and the initial fraction u of voters with opinion 1. In case (i), there is a critical value alpha(c) which does not depend on u, with rho approximate to u for alpha > alpha(c) and rho approximate to 0 for alpha < alpha(c). In case (ii), the transition point alpha(c)(u) depends on the initial density u. For a > alpha(c)(u), rho approximate to u, but for alpha < alpha(c)(u), we have rho(alpha,u) = rho(alpha, 1/2). Using simulations and approximate calculations, we explain why these two nearly identical models have such dramatically different phase transitions.
C1 [Durrett, Richard; Sivakoff, David] Duke Univ, Dept Math, Durham, NC 27708 USA.
   [Gleeson, James P.] Univ Limerick, Dept Math & Stat, Math Applicat Consortium Sci Ind, Limerick, Ireland.
   [Lloyd, Alun L.] N Carolina State Univ, Dept Math, Raleigh, NC 27695 USA.
   [Lloyd, Alun L.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
   [Shi, Feng] Univ N Carolina, Dept Math, Chapel Hill, NC 27599 USA.
   [Socolar, Joshua E. S.; Varghese, Chris] Duke Univ, Dept Phys, Durham, NC 27708 USA.
RP Durrett, R (reprint author), Duke Univ, Dept Math, Box 90320, Durham, NC 27708 USA.
EM rtd@math.duke.edu
RI Lloyd, Alun/H-4944-2012; Gleeson, James/G-1595-2014; 
OI Socolar, Joshua/0000-0003-0532-7099; Gleeson, James/0000-0003-3410-2817
FU National Science Foundation [DMS-1005470, DMS-0645369]; Science
   Foundation Ireland [06/IN.1/I366]; Mathematics Applications Consortium
   for Science and Industry [06/MI/005]; National Institutes of Health
FX The authors thank Raissa D'Souza, Eric Kolaczyk, Tom Liggett, and Mason
   Porter for their many helpful suggestions. This work began during the
   2010-2011 program on Complex Networks at the Statistical and Applied
   Mathematical Sciences Institute. This work was partially supported by
   National Science Foundation Grants DMS-1005470 (to R.D.) and DMS-0645369
   (to P.J.M.), by Science Foundation Ireland Grants 06/IN.1/I366, and
   Mathematics Applications Consortium for Science and Industry 06/MI/005
   (to J.P.G.), and by the Research and Policy for Infectious Disease
   Dynamics program at National Institutes of Health (A.L.L.).
NR 49
TC 37
Z9 39
U1 1
U2 18
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 MAR 6
PY 2012
VL 109
IS 10
BP 3682
EP 3687
DI 10.1073/pnas.1200709109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 903LJ
UT WOS:000301117700023
PM 22355142
ER

PT J
AU Carvajal-Gonzalez, JM
   Gravotta, D
   Mattera, R
   Diaz, F
   Bay, AP
   Roman, AC
   Schreiner, RP
   Thuenauer, R
   Bonifacino, JS
   Rodriguez-Boulan, E
AF Carvajal-Gonzalez, Jose Maria
   Gravotta, Diego
   Mattera, Rafael
   Diaz, Fernando
   Bay, Andres Perez
   Roman, Angel C.
   Schreiner, Ryan P.
   Thuenauer, Roland
   Bonifacino, Juan S.
   Rodriguez-Boulan, Enrique
TI Basolateral sorting of the coxsackie and adenovirus receptor through
   interaction of a canonical YXX Phi motif with the clathrin adaptors
   AP-1A and AP-1B
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE trans-Golgi network; recycling endosomes; exocytosis; epithelial cells;
   protein sorting
ID POLARIZED EPITHELIAL-CELLS; TRANS-GOLGI NETWORK; HIV-1 ENVELOPE
   GLYCOPROTEIN; CANINE KIDNEY-CELLS; MDCK CELLS; CYTOPLASMIC DOMAIN;
   TARGETING SIGNAL; LDL RECEPTOR; TYROSINE; TRAFFICKING
AB The coxsackie and adenovirus receptor (CAR) plays key roles in epithelial barrier function at the tight junction, a localization guided in part by a tyrosine-based basolateral sorting signal, (318)YNQV(321). Sorting motifs of this type are known to route surface receptors into clathrin-mediated endocytosis through interaction with the medium subunit (mu 2) of the clathrin adaptor AP-2, but how they guide new and recycling membrane proteins basolaterally is unknown. Here, we show that YNQV functions as a canonical YXX Phi motif, with both Y318 and V321 required for the correct basolateral localization and biosynthetic sorting of CAR, and for interaction with a highly conserved pocket in the medium subunits (mu 1A and mu 1B) of the clathrin adaptors AP-1A and AP-1B. Knock-down experiments demonstrate that AP-1A plays a role in the biosynthetic sorting of CAR, complementary to the role of AP-1B in basolateral recycling of this receptor. Our study illustrates how two clathrin adaptors direct basolateral trafficking of a plasma membrane protein through interaction with a canonical YXX Phi motif.
C1 [Mattera, Rafael; Bonifacino, Juan S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
   [Carvajal-Gonzalez, Jose Maria; Gravotta, Diego; Bay, Andres Perez; Schreiner, Ryan P.; Rodriguez-Boulan, Enrique] Weill Cornell Med Coll, Margaret Dyson Vis Res Inst, Dept Physiol & Biophys, Dept Cell & Dev Biol,Dept Ophthalmol, New York, NY 10065 USA.
   [Diaz, Fernando] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.
   [Roman, Angel C.] CSIC, Inst Cajal, E-28002 Madrid, Spain.
   [Thuenauer, Roland] Ctr Adv Bioanal Linz GmbH, A-4020 Linz, Austria.
RP Bonifacino, JS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
EM juan@helix.nih.gov; boulan@med.cornell.edu
OI Carvajal-Gonzalez, Jose Maria/0000-0001-6576-830X
FU National Institutes of Health [EY08538, GM34107]; European Molecular
   Biology Organization; Dyson Foundation; Research to Prevent Blindness
   Foundation; Eunice Kennedy Shriver National Institute of Child Health
   and Human Development
FX This work was supported by National Institutes of Health Grants EY08538
   and GM34107 (to E.R.-B.); a European Molecular Biology Organization
   fellowship (to J.M.C.-G.); the Dyson Foundation and by the Research to
   Prevent Blindness Foundation; and by the Intramural Program of the
   Eunice Kennedy Shriver National Institute of Child Health and Human
   Development (R. M. and J.S.B.).
NR 51
TC 43
Z9 43
U1 0
U2 11
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 MAR 6
PY 2012
VL 109
IS 10
BP 3820
EP 3825
DI 10.1073/pnas.1117949109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 903LJ
UT WOS:000301117700047
PM 22343291
ER

PT J
AU Diril, MK
   Ratnacaram, CK
   Padmakumar, VC
   Du, TH
   Wasser, M
   Coppola, V
   Tessarollo, L
   Kaldis, P
AF Diril, M. Kasim
   Ratnacaram, Chandrahas Koumar
   Padmakumar, V. C.
   Du, Tiehua
   Wasser, Martin
   Coppola, Vincenzo
   Tessarollo, Lino
   Kaldis, Philipp
TI Cyclin-dependent kinase 1 (Cdk1) is essential for cell division and
   suppression of DNA re-replication but not for liver regeneration
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE cancer; knockout mice; cell cycle regulation; polyploidy
ID EMBRYONIC LETHALITY; EUKARYOTIC CELLS; PHASE; CANCER; MICE;
   TUMORIGENESIS; INHIBITION; MECHANISMS; TRANSITION; P27(KIP1)
AB Cyclin-dependent kinase 1 (Cdk1) is an archetypical kinase and a central regulator that drives cells through G2 phase and mitosis. Knockouts of Cdk2, Cdk3, Cdk4, or Cdk6 have resulted in viable mice, but the in vivo functions of Cdk1 have not been fully explored in mammals. Here we have generated a conditional-knockout mouse model to study the functions of Cdk1 in vivo. Ablation of Cdk1 leads to arrest of embryonic development around the blastocyst stage. Interestingly, liver-specific deletion of Cdk1 is well tolerated, and liver regeneration after partial hepatectomy is not impaired, indicating that regeneration can be driven by cell growth without cell division. The loss of Cdk1 does not affect S phase progression but results in DNA re-replication because of an increase in Cdk2/cyclin A2 activity. Unlike other Cdks, loss of Cdk1 in the liver confers complete resistance against tumorigenesis induced by activated Ras and silencing of p53.
C1 [Kaldis, Philipp] Natl Univ Singapore, Dept Biochem, Singapore 117597, Singapore.
   [Wasser, Martin] Natl Univ Singapore, Dept Biol Sci, Singapore 117597, Singapore.
   [Padmakumar, V. C.; Coppola, Vincenzo; Tessarollo, Lino] NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA.
EM kaldis@imcb.a-star.edu.sg
RI Kaldis, Philipp/G-2714-2010; Coppola, Vincenzo/E-2917-2011; ASTAR,
   IMCB/E-2320-2012; 
OI Kaldis, Philipp/0000-0002-7247-7591; Coppola,
   Vincenzo/0000-0001-6163-1779; Wasser, Martin/0000-0002-8753-2346
FU Biomedical Research Council of the Agency for Science, Technology, and
   Research (A*STAR), Singapore
FX We thank Eileen Southon and Susan Reid for help in generating the
   Cdk1<SUP>FLOX/FLOX</SUP> mice, and David Largaespada for
   transposase/transposon constructs. We appreciate that Jos Jonkers and
   Anton Berns provided the ROSA26-CreERT2 mice, Andy McMahon the Cre-Esr1
   mice, Mark Lewandoski the beta-actin-Cre/Flpe mice, and T. Jake Liang
   the albumin-Cre mice. We thank Nancy Jenkins and Neal Copeland for
   advice, suggestions, reagents, and support. We are thankful to Cyril
   Berthet for reagents and discussion as well as to Steve Cohen and Neal
   Copeland for comments on the manuscript. We also thank Davor Solter and
   Barbara Knowles for technical advice; June Wang, Chloe Sim, and Vithya
   Anantaraja for animal care; Keith Rogers, Susan Rogers, and the
   technicians of the Pathology/Histotechnology Laboratory for superb
   analysis of mouse pathology; and the P. K. laboratory for support and
   discussions. This work was supported by the Biomedical Research Council
   of the Agency for Science, Technology, and Research (A*STAR), Singapore.
NR 35
TC 71
Z9 71
U1 1
U2 11
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 MAR 6
PY 2012
VL 109
IS 10
BP 3826
EP 3831
DI 10.1073/pnas.1115201109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 903LJ
UT WOS:000301117700048
PM 22355113
ER

PT J
AU Zhang, M
   Mishra, S
   Sakthivel, R
   Rojas, M
   Ranjan, R
   Sullivan, WJ
   Fontoura, BMA
   Menard, R
   Dever, TE
   Nussenzweig, V
AF Zhang, Min
   Mishra, Satish
   Sakthivel, Ramanavelan
   Rojas, Margarito
   Ranjan, Ravikant
   Sullivan, William J., Jr.
   Fontoura, Beatriz M. A.
   Menard, Robert
   Dever, Thomas E.
   Nussenzweig, Victor
TI PK4, a eukaryotic initiation factor 2 alpha(eIF2 alpha) kinase, is
   essential for the development of the erythrocytic cycle of Plasmodium
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID MAMMALIAN STRESS GRANULES; MALARIA PARASITES; TOXOPLASMA-GONDII;
   PROTEIN-KINASES; FALCIPARUM; PHOSPHORYLATION; FACTOR-2-ALPHA;
   LOCALIZATION; MUTAGENESIS; RESISTANCE
AB In response to environmental stresses, the mammalian serine threonine kinases PERK, GCN2, HRI, and PKR phosphorylate the regulatory serine 51 of the eukaryotic translation initiation factor 2 alpha(eIF2 alpha) to inhibit global protein synthesis. Plasmodium, the protozoan that causes malaria, expresses three eIF2 alpha kinases: IK1, IK2, and PK4. Like GCN2, IK1 regulates stress response to amino acid starvation. IK2 inhibits development of malaria sporozoites present in the mosquito salivary glands. Here we show that the phosphorylation by PK4 of the regulatory serine 59 of Plasmodium eIF2 alpha is essential for the completion of the parasite's erythrocytic cycle that causes disease in humans. PK4 activity leads to the arrest of global protein synthesis in schizonts, where ontogeny of daughter merozoites takes place, and in gametocytes that infect Anopheles mosquitoes. The implication of these findings is that drugs that reduce PK4 activity should alleviate disease and inhibit malaria transmission.
C1 [Zhang, Min; Mishra, Satish; Ranjan, Ravikant; Nussenzweig, Victor] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA.
   [Sakthivel, Ramanavelan; Fontoura, Beatriz M. A.] Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA.
   [Rojas, Margarito; Dever, Thomas E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
   [Sullivan, William J., Jr.] Indiana Univ Sch Med, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 USA.
   [Menard, Robert] Inst Pasteur, Unite Biol & Genet Paludisme, F-75015 Paris, France.
RP Nussenzweig, V (reprint author), NYU, Sch Med, Dept Pathol, New York, NY 10016 USA.
EM victor.nussenzweig@nyumc.org
RI Zhang, Min/G-4480-2011; Mishra, Satish/K-7473-2015; 
OI Zhang, Min/0000-0001-9794-4523; Mishra, Satish/0000-0002-8942-6416;
   Dever, Thomas/0000-0001-7120-9678
FU National Institutes of Health [AI084031, AI077502, R01 GM067159]
FX This work was supported by National Institutes of Health Grants AI084031
   and AI077502 (to W.J.S.); the Intramural Research Program of the
   National Institutes of Health (T.E.D.); and National Institutes of
   Health Grant R01 GM067159 (to B.M.A.F.).
NR 38
TC 30
Z9 31
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 MAR 6
PY 2012
VL 109
IS 10
BP 3956
EP 3961
DI 10.1073/pnas.1121567109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 903LJ
UT WOS:000301117700070
PM 22355110
ER

PT J
AU Lu, HB
   Zou, QH
   Gu, H
   Raichle, ME
   Stein, EA
   Yang, YH
AF Lu, Hanbing
   Zou, Qihong
   Gu, Hong
   Raichle, Marcus E.
   Stein, Elliot A.
   Yang, Yihong
TI Rat brains also have a default mode network
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE functional MRI; resting state; intrinsic activity; connectivity;
   spontaneous fluctuation
ID PREFRONTAL CORTICAL PROJECTIONS; INDEPENDENT COMPONENT ANALYSIS;
   PARIETAL ASSOCIATION CORTEX; RESTING-STATE CONNECTIVITY; FUNCTIONAL
   CONNECTIVITY; MACAQUE MONKEYS; AFFERENT CONNECTIONS; LONGITUDINAL
   COLUMNS; PERIAQUEDUCTAL GRAY; ORBITAL CORTEX
AB The default mode network (DMN) in humans has been suggested to support a variety of cognitive functions and has been implicated in an array of neuropsychological disorders. However, its function (s) remains poorly understood. We show that rats possess a DMN that is broadly similar to the DMNs of nonhuman primates and humans. Our data suggest that, despite the distinct evolutionary paths between rodent and primate brain, a well-organized, intrinsically coherent DMN appears to be a fundamental feature in the mammalian brain whose primary functions might be to integrate multimodal sensory and affective information to guide behavior in anticipation of changing environmental contingencies.
C1 [Raichle, Marcus E.] Washington Univ, Dept Radiol, St Louis, MO 63110 USA.
   [Raichle, Marcus E.] Washington Univ, Dept Neurol, St Louis, MO 63110 USA.
   [Raichle, Marcus E.] Washington Univ, Dept Anat & Neurobiol, St Louis, MO 63110 USA.
   [Raichle, Marcus E.] Washington Univ, Dept Biomed Engn, St Louis, MO 63110 USA.
   [Lu, Hanbing; Zou, Qihong; Gu, Hong; Stein, Elliot A.; Yang, Yihong] NIDA, Neuroimaging Res Branch, Intramural Res Programs, NIH, Baltimore, MD 21224 USA.
   [Zou, Qihong] Peking Univ, MRI Res Ctr, Beijing 100871, Peoples R China.
   [Zou, Qihong] Peking Univ, Beijing City Key Lab Med Phys & Engn, Beijing 100871, Peoples R China.
RP Raichle, ME (reprint author), Washington Univ, Dept Radiol, St Louis, MO 63110 USA.
EM marc@npg.wustl.edu; estein@intra.nida.nih.gov;
   yihongyang@intra.nida.nih.gov
FU National Institute on Drug Abuse, National Institutes of Health;
   National Institute of Neurological Disorders and Stroke [NS06833];
   China's National Strategic Basic Research Program ("973") [2012CB720700]
FX We acknowledge the invaluable assistance of Joseph L. Price, Professor
   of Anatomy and Neurobiology, Washington University School of Medicine,
   who gave generously of his time in helping us interpret our imaging
   findings in the context of rat brain anatomy. This study is supported by
   the Intramural Research Program of the National Institute on Drug Abuse,
   National Institutes of Health. M.E.R. is supported by Grant NS06833 from
   the National Institute of Neurological Disorders and Stroke. Q.Z. is
   supported by China's National Strategic Basic Research Program ("973")
   Grant 2012CB720700.
NR 60
TC 140
Z9 144
U1 5
U2 30
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 MAR 6
PY 2012
VL 109
IS 10
BP 3979
EP 3984
DI 10.1073/pnas.1200506109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 903LJ
UT WOS:000301117700074
PM 22355129
ER

PT J
AU Kolbe, DL
   DeLoia, JA
   Porter-Gill, P
   Strange, M
   Petrykowska, HM
   Guirguis, A
   Krivak, TC
   Brody, LC
   Elnitski, L
AF Kolbe, Diana L.
   DeLoia, Julie A.
   Porter-Gill, Patricia
   Strange, Mary
   Petrykowska, Hanna M.
   Guirguis, Alfred
   Krivak, Thomas C.
   Brody, Lawrence C.
   Elnitski, Laura
TI Differential Analysis of Ovarian and Endometrial Cancers Identifies a
   Methylator Phenotype
SO PLOS ONE
LA English
DT Article
ID SEROUS CARCINOMA; GENE-EXPRESSION; LOW-GRADE; PATHWAYS; MODEL;
   MUTATIONS; TUMORS; CARCINOGENESIS; PROFILES; PATTERNS
AB Despite improved outcomes in the past 30 years, less than half of all women diagnosed with epithelial ovarian cancer live five years beyond their diagnosis. Although typically treated as a single disease, epithelial ovarian cancer includes several distinct histological subtypes, such as papillary serous and endometrioid carcinomas. To address whether the morphological differences seen in these carcinomas represent distinct characteristics at the molecular level we analyzed DNA methylation patterns in 11 papillary serous tumors, 9 endometrioid ovarian tumors, 4 normal fallopian tube samples and 6 normal endometrial tissues, plus 8 normal fallopian tube and 4 serous samples from TCGA. For comparison within the endometrioid subtype we added 6 primary uterine endometrioid tumors and 5 endometrioid metastases from uterus to ovary. Data was obtained from 27,578 CpG dinucleotides occurring in or near promoter regions of 14,495 genes. We identified 36 locations with significant increases or decreases in methylation in comparisons of serous tumors and normal fallopian tube samples. Moreover, unsupervised clustering techniques applied to all samples showed three major profiles comprising mostly normal samples, serous tumors, and endometrioid tumors including ovarian, uterine and metastatic origins. The clustering analysis identified 60 differentially methylated sites between the serous group and the normal group. An unrelated set of 25 serous tumors validated the reproducibility of the methylation patterns. In contrast, >1,000 genes were differentially methylated between endometrioid tumors and normal samples. This finding is consistent with a generalized regulatory disruption caused by a methylator phenotype. Through DNA methylation analyses we have identified genes with known roles in ovarian carcinoma etiology, whereas pathway analyses provided biological insight to the role of novel genes. Our finding of differences between serous and endometrioid ovarian tumors indicates that intervention strategies could be developed to specifically address subtypes of epithelial ovarian cancer.
C1 [Kolbe, Diana L.; Petrykowska, Hanna M.; Elnitski, Laura] NHGRI, DIR GTB Genom Funct Anal Sect, NIH, Bethesda, MD 20892 USA.
   [Porter-Gill, Patricia; Brody, Lawrence C.] NHGRI, DIR GTB Mol Pathogenesis Sect, NIH, Bethesda, MD 20892 USA.
   [DeLoia, Julie A.; Strange, Mary; Krivak, Thomas C.] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA.
   [DeLoia, Julie A.] George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC USA.
   [Guirguis, Alfred] Rush Univ, Dept Obstet & Gynecol, Chicago, IL 60612 USA.
RP Kolbe, DL (reprint author), NHGRI, DIR GTB Genom Funct Anal Sect, NIH, Bethesda, MD 20892 USA.
EM elnitski@mail.nih.gov
OI Strange, Mary/0000-0003-3269-4185
FU National Human Genome Research Institute, National Institutes of Health;
   DoD GOC [04-124]; Magee Womens Research Institute
FX Funding is provided by The Intramural Research Program of the National
   Human Genome Research Institute, National Institutes of Health (LE and
   LB), DoD GOC# 04-124 and Magee Womens Research Institute/Scaife Grant
   (TCK). The funders had no role in study design, data collection and
   analysis, decision to publish, or preparation of the manuscript.
NR 40
TC 11
Z9 12
U1 0
U2 1
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 MAR 5
PY 2012
VL 7
IS 3
AR e32941
DI 10.1371/journal.pone.0032941
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 928WA
UT WOS:000303017700123
PM 22403726
ER

PT J
AU Chamberlain, BT
   Batra, VK
   Beard, WA
   Kadina, AP
   Shock, DD
   Kashemirov, BA
   McKenna, CE
   Goodman, MF
   Wilson, SH
AF Chamberlain, Brian T.
   Batra, Vinod K.
   Beard, William A.
   Kadina, Anastasia P.
   Shock, David D.
   Kashemirov, Boris A.
   McKenna, Charles E.
   Goodman, Myron F.
   Wilson, Samuel H.
TI Stereospecific Formation of a Ternary Complex of
   (S)-alpha,beta-Fluoromethylene-dATP with DNA Pol beta
SO CHEMBIOCHEM
LA English
DT Article
DE enzymes; fluorine; inhibitors; nucleotides
ID POLYMERASE-BETA; 5'-TRIPHOSPHATES; ANALOGS; FIDELITY; REPAIR
C1 [Chamberlain, Brian T.; Kadina, Anastasia P.; Kashemirov, Boris A.; McKenna, Charles E.; Goodman, Myron F.] Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA.
   [Chamberlain, Brian T.; Kadina, Anastasia P.; Kashemirov, Boris A.; McKenna, Charles E.; Goodman, Myron F.] Univ So Calif, Dept Biol, Los Angeles, CA 90089 USA.
   [Batra, Vinod K.; Beard, William A.; Shock, David D.; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
RP McKenna, CE (reprint author), Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA.
EM mckenna@usc.edu; wilson5@niehs.nih.gov
FU NIH [U19CA105010]; National Institutes of Health, National Institute of
   Environmental Health Sciences [Z01ES050158]
FX This research was supported by NIH grant U19CA105010 and in part by the
   Intramural Research Program of the National Institutes of Health,
   National Institute of Environmental Health Sciences, project number
   Z01ES050158. We thank Inah Kang for assistance in preparing the
   manuscript.
NR 18
TC 16
Z9 17
U1 0
U2 7
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY
SN 1439-4227
J9 CHEMBIOCHEM
JI ChemBioChem
PD MAR 5
PY 2012
VL 13
IS 4
BP 528
EP 530
DI 10.1002/cbic.201100738
PG 3
WC Biochemistry & Molecular Biology; Chemistry, Medicinal
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 900FI
UT WOS:000300871600008
PM 22315190
ER

PT J
AU Shah, SS
   Diakite, SAS
   Traore, K
   Diakite, M
   Kwiatkowski, DP
   Rockett, KA
   Wellems, TE
   Fairhurst, RM
AF Shah, Shivang S.
   Diakite, Seidina A. S.
   Traore, Karim
   Diakite, Mahamadou
   Kwiatkowski, Dominic P.
   Rockett, Kirk A.
   Wellems, Thomas E.
   Fairhurst, Rick M.
TI A novel cytofluorometric assay for the detection and quantification of
   glucose-6-phosphate dehydrogenase deficiency
SO SCIENTIFIC REPORTS
LA English
DT Article
ID DEHYDROGENASE DEFICIENCY; LIPID-PEROXIDATION; HUMAN-ERYTHROCYTES;
   HYDROGEN-PEROXIDE; RED CELLS; G6PD; FLUORESCENCE; HEMOGLOBIN; HEME;
   LOCALIZATION
AB Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked enzymopathy that affects hundreds of millions of people worldwide, conferring increased risk of neonatal jaundice and oxidant-induced hemolytic anemia. Screening and diagnosis of G6PD deficiency is currently performed using genetic or biochemical assays, the former being cost ineffective in populations with significant allelic heterogeneity, and the latter being limited in ability to detect female heterozygotes. Cytochemical assays can obviate these shortcomings, but at the expense of added technical complexity and labor. We describe here a simple, novel cytofluorometric method that extends the classic methemoglobin reduction test, assessing G6PD deficiency at the level of an individual erythrocyte. In preliminary testing in Malian children, there was strong concordance between our method and established genetic and biochemical techniques. The assay is robust and economical, and could serve as a screening method as well as a research tool, especially for high-throughput applications such as flow cytometry.
C1 [Shah, Shivang S.; Wellems, Thomas E.; Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
   [Shah, Shivang S.; Kwiatkowski, Dominic P.; Rockett, Kirk A.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
   [Diakite, Seidina A. S.; Traore, Karim; Diakite, Mahamadou] Univ Bamako, Fac Med Pharm & Odontostomatol, Malaria Res & Training Ctr, Bamako, Mali.
RP Fairhurst, RM (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM rfairhurst@niaid.nih.gov
OI Kwiatkowski, Dominic/0000-0002-5023-0176
FU NIAID, NIH
FX We thank all the children and their families who participated in this
   study, and Saibou Doumbia, Drissa Konate, Mory Doumbia, and Dick Sakai
   for their efforts in support of this work. This study was supported by
   the Intramural Research Program of the NIAID, NIH.
NR 38
TC 18
Z9 18
U1 0
U2 8
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 MAR 5
PY 2012
VL 2
AR 299
DI 10.1038/srep00299
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 905TN
UT WOS:000301297900001
PM 22393475
ER

PT J
AU Gopich, IV
AF Gopich, Irina V.
TI Likelihood functions for the analysis of single-molecule binned photon
   sequences
SO CHEMICAL PHYSICS
LA English
DT Article
DE Single molecule fluorescence spectroscopy; FRET; Hidden Markov models;
   Three-color FRET
ID RESONANCE ENERGY-TRANSFER; HIDDEN MARKOV-MODELS; MODULATED
   POISSON-PROCESS; CONFORMATIONAL DYNAMICS; FRET; FLUORESCENCE;
   TRAJECTORIES; PROTEIN; KINETICS; SPECTROSCOPY
AB We consider the analysis of a class of experiments in which the number of photons in consecutive time intervals is recorded. Sequence of photon counts or, alternatively, of FRET efficiencies can be studied using likelihood-based methods. For a kinetic model of the conformational dynamics and state-dependent Poisson photon statistics, the formalism to calculate the exact likelihood that this model describes such sequences of photons or FRET efficiencies is developed. Explicit analytic expressions for the likelihood function for a two-state kinetic model are provided. The important special case when conformational dynamics are so slow that at most a single transition occurs in a time bin is considered. By making a series of approximations, we eventually recover the likelihood function used in hidden Markov models. In this way, not only is insight gained into the range of validity of this procedure, but also an improved likelihood function can be obtained. Published by Elsevier B.V.
C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Gopich, IV (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA.
EM irinag@niddk.nih.gov
FU National Institutes of Health, NIDDK
FX I thank A. Szabo for numerous extremely illuminating discussions, H. S.
   Chung for Fig. 1(a), and A. Berezhkovskii for helpful comments on the
   manuscript. This work was supported by the Intramural Research Program
   of the National Institutes of Health, NIDDK.
NR 34
TC 4
Z9 4
U1 0
U2 14
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0301-0104
J9 CHEM PHYS
JI Chem. Phys.
PD MAR 2
PY 2012
VL 396
BP 53
EP 60
DI 10.1016/j.chemphys.2011.06.006
PG 8
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 925NH
UT WOS:000302767400008
PM 22711967
ER

PT J
AU Di Lieto, A
   Rantamaki, T
   Vesa, L
   Yanpallewar, S
   Antila, H
   Lindholm, J
   Rios, M
   Tessarollo, L
   Castren, E
AF Di Lieto, Antonio
   Rantamaki, Tomi
   Vesa, Liisa
   Yanpallewar, Sudhirkumar
   Antila, Hanna
   Lindholm, Jesse
   Rios, Maribel
   Tessarollo, Lino
   Castren, Eero
TI The Responsiveness of TrkB to BDNF and Antidepressant Drugs Is
   Differentially Regulated during Mouse Development
SO PLOS ONE
LA English
DT Article
ID NEUROTROPHIC FACTOR; HIPPOCAMPAL-NEURONS; TRUNCATED TRKB.T1; BRAIN;
   RECEPTOR; MICE; DEPRESSION; PLASTICITY; MODULATION; ACTIVATION
AB Background: Previous studies suggest that the responsiveness of TrkB receptor to BDNF is developmentally regulated in rats. Antidepressant drugs (AD) have been shown to increase TrkB signalling in the adult rodent brain, and recent findings implicate a BDNF-independent mechanism behind this phenomenon. When administered during early postnatal life, ADs produce long-lasting biochemical and behavioural alterations that are observed in adult animals.
   Methodology: We have here examined the responsiveness of brain TrkB receptors to BDNF and ADs during early postnatal life of mouse, measured as autophosphorylation of TrkB (pTrkB).
   Principal Findings: We found that ADs fail to induce TrkB signalling before postnatal day 12 (P12) after which an adult response of TrkB to ADs was observed. Interestingly, there was a temporally inverse correlation between the appearance of the responsiveness of TrkB to systemic ADs and the marked developmental reduction of BDNF-induced TrkB in brain microslices ex vivo. Basal p-TrkB status in the brain of BDNF deficient mice was significantly reduced only during early postnatal period. Enhancing cAMP (cyclic adenosine monophosphate) signalling failed to facilitate TrkB responsiveness to BDNF. Reduced responsiveness of TrkB to BDNF was not produced by the developmental increase in the expression of dominant-negative truncated TrkB. T1 because this reduction was similarly observed in the brain microslices of trkB. T1(-/-) mice. Moreover, postnatal AD administration produced long-lasting behavioural alterations observable in adult mice, but the responses were different when mice were treated during the time when ADs did not (P4-9) or did (P16-21) activate TrkB.
   Conclusions: We have found that ADs induce the activation of TrkB only in mice older than 2 weeks and that responsiveness of brain microslices to BDNF is reduced during the same time period. Exposure to ADs before and after the age when ADs activate TrkB produces differential long-term behavioural responses in adult mice.
C1 [Di Lieto, Antonio; Rantamaki, Tomi; Vesa, Liisa; Antila, Hanna; Lindholm, Jesse; Castren, Eero] Univ Helsinki, Neurosci Ctr, Sigrid Juselius Lab, Helsinki, Finland.
   [Yanpallewar, Sudhirkumar; Tessarollo, Lino] NCI, Neural Dev Sect, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21701 USA.
   [Rios, Maribel] Tufts Univ, Sch Med, Dept Neurosci, Boston, MA 02111 USA.
RP Di Lieto, A (reprint author), Univ Helsinki, Neurosci Ctr, Sigrid Juselius Lab, Helsinki, Finland.
EM eero.castren@helsinki.fi
OI Antila, Hanna/0000-0001-8317-4564; Rantamaki, Tomi/0000-0002-0052-1434;
   Castren, Eero/0000-0002-1402-2791
FU Academy of Finland Center of Excellence; Helsinki Graduate Program in
   Biotechnology and Molecular Biology; Sigrid Juselius Foundation; United
   States National Institutes of Health, National Cancer Institute
FX This study was financially supported by the Academy of Finland Center of
   Excellence Programme (E. C.), the Helsinki Graduate Program in
   Biotechnology and Molecular Biology (L. V.), the Sigrid Juselius
   Foundation (E. C.) and Intramural Research Program of the United States
   National Institutes of Health, National Cancer Institute (S.Y. and L.
   T.). The funders had no role in study design, data collection and
   analysis, decision to publish, or preparation of the manuscript.
NR 41
TC 13
Z9 13
U1 1
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 MAR 2
PY 2012
VL 7
IS 3
AR e32869
DI 10.1371/journal.pone.0032869
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 928TC
UT WOS:000303006500035
PM 22396798
ER

PT J
AU Patrick, H
   Williams, GC
AF Patrick, Heather
   Williams, Geoffrey C.
TI Self-determination theory: its application to health behavior and
   complementarity with motivational interviewing
SO INTERNATIONAL JOURNAL OF BEHAVIORAL NUTRITION AND PHYSICAL ACTIVITY
LA English
DT Review
ID RANDOMIZED CONTROLLED-TRIAL; INTRINSIC MOTIVATION; MEDICATION ADHERENCE;
   SUPPORTING AUTONOMY; PHYSICAL-ACTIVITY; PROBLEM DRINKERS;
   DECISION-MAKING; AMERICAN-DREAM; WEIGHT CONTROL; INTERVENTION
AB Mounting evidence implicates health behaviors (e.g., nutrition, physical activity, tobacco abstinence) in various health outcomes. As the science of behavior change has emerged, increasing emphasis has been placed on the use of theory in developing and testing interventions. Self-determination theory (SDT)-a theoretical perspective-and motivational interviewing (MI)-a set of clinical techniques-have both been used in health behavior intervention contexts. Although developed for somewhat different purposes and in relatively different domains, there is a good deal of conceptual overlap between SDT and MI. Accordingly, SDT may offer the theoretical backing that historically has been missing from MI, and MI may offer SDT some specific direction with respect to particular clinical techniques that have not been fully borne out within the confines of health related applications of SDT. Research is needed to empirically test the overlap and distinctions between SDT and MI and to determine the extent to which these two perspectives can be combined or co-exist as somewhat distinct approaches.
C1 [Patrick, Heather] NCI, Div Canc Control & Populat Sci, Rockville, MD 20852 USA.
   [Williams, Geoffrey C.] Univ Rochester, Dept Med & Clin & Social Psychol, Rochester, NY 14607 USA.
RP Patrick, H (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd, Rockville, MD 20852 USA.
EM patrickha@mail.nih.gov
NR 71
TC 50
Z9 51
U1 11
U2 54
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5868
J9 INT J BEHAV NUTR PHY
JI Int. J. Behav. Nutr. Phys. Act.
PD MAR 2
PY 2012
VL 9
AR 18
DI 10.1186/1479-5868-9-18
PG 12
WC Nutrition & Dietetics; Physiology
SC Nutrition & Dietetics; Physiology
GA 921MC
UT WOS:000302480700001
PM 22385676
ER

PT J
AU Verstuyf, J
   Patrick, H
   Vansteenkiste, M
   Teixeira, PJ
AF Verstuyf, Joke
   Patrick, Heather
   Vansteenkiste, Maarten
   Teixeira, Pedro J.
TI Motivational dynamics of eating regulation: a self-determination theory
   perspective
SO INTERNATIONAL JOURNAL OF BEHAVIORAL NUTRITION AND PHYSICAL ACTIVITY
LA English
DT Review
DE Eating Regulation; Eating Disorders; Self-Determination Theory;
   Motivation; Autonomous Regulation; Need Substitutes; Thin-Ideal
ID PARENTAL PSYCHOLOGICAL CONTROL; WEIGHT-LOSS MAINTENANCE; INTRINSIC
   MOTIVATION; BODY-IMAGE; MALADAPTIVE PERFECTIONISM; DISORDER PATIENTS;
   BULIMIC SYMPTOMS; AUTONOMY SUPPORT; WOMEN; OBJECTIFICATION
AB Within Western society, many people have difficulties adequately regulating their eating behaviors and weight. Although the literature on eating regulation is vast, little attention has been given to motivational dynamics involved in eating regulation. Grounded in Self-Determination Theory (SDT), the present contribution aims to provide a motivational perspective on eating regulation. The role of satisfaction and thwarting of the basic psychological needs for autonomy, competence, and relatedness is introduced as a mechanism to (a) explain the etiology of body image concerns and disordered eating and (b) understand the optimal regulation of ongoing eating behavior for healthy weight maintenance. An overview of empirical studies on these two research lines is provided. In a final section, the potential relevance and value of SDT in relation to prevailing theoretical models in the domain of eating regulation is discussed. Although research on SDT in the domain of eating regulation is still in its early stages and more research is clearly needed, this review suggests that the SDT represents a promising framework to more thoroughly study and understand the motivational processes involved in eating regulation and associated problems.
C1 [Verstuyf, Joke; Vansteenkiste, Maarten] Univ Ghent, Dept Dev Personal & Social Psychol, B-9000 Ghent, Belgium.
   [Patrick, Heather] NCI, Rockville, MD 20852 USA.
   [Teixeira, Pedro J.] Univ Tecn Lisboa, Fac Human Kinet, P-1495688 Cruz Quebrada, Portugal.
RP Verstuyf, J (reprint author), Univ Ghent, Dept Dev Personal & Social Psychol, H Dunantlaan 2, B-9000 Ghent, Belgium.
EM Joke.Verstuyf@UGent.be
RI Teixeira, Pedro/C-9817-2010
OI Teixeira, Pedro/0000-0001-7202-0527
FU Fund for Scientific Research-Flanders (FWO), Belgium
FX We acknowledge Bart Soenens and Liesbet Boone for critically reading the
   manuscript and giving useful suggestions to improve the quality of the
   manuscript. We thank Richard Ryan for discussing theoretical statements
   and providing feedback on the figures attached to this manuscript. The
   first author, JV, is funded as a Research Assistant of the Fund for
   Scientific Research-Flanders (FWO), Belgium.
NR 108
TC 31
Z9 31
U1 7
U2 62
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5868
J9 INT J BEHAV NUTR PHY
JI Int. J. Behav. Nutr. Phys. Act.
PD MAR 2
PY 2012
VL 9
AR 21
DI 10.1186/1479-5868-9-21
PG 16
WC Nutrition & Dietetics; Physiology
SC Nutrition & Dietetics; Physiology
GA 916FC
UT WOS:000302083500001
PM 22385782
ER

PT J
AU Cheng, LZ
   Hansen, NF
   Zhao, L
   Du, YT
   Zou, CL
   Donovan, FX
   Chou, BK
   Zhou, GY
   Li, SJ
   Dowey, SN
   Ye, ZH
   Chandrasekharappa, SC
   Yang, HM
   Mullikin, JC
   Liu, PP
AF Cheng, Linzhao
   Hansen, Nancy F.
   Zhao, Ling
   Du, Yutao
   Zou, Chunlin
   Donovan, Frank X.
   Chou, Bin-Kuan
   Zhou, Guangyu
   Li, Shijie
   Dowey, Sarah N.
   Ye, Zhaohui
   Chandrasekharappa, Settara C.
   Yang, Huanming
   Mullikin, James C.
   Liu, P. Paul
CA NISC Comparative Sequencing Progra
TI Low Incidence of DNA Sequence Variation in Human Induced Pluripotent
   Stem Cells Generated by Nonintegrating Plasmid Expression
SO CELL STEM CELL
LA English
DT Article
ID COPY NUMBER VARIATION; GENOME; MUTATIONS; ACCURATE; DERIVATION;
   SPECTRUM; CULTURE; GENES
AB The utility of induced pluripotent stem cells (iPSCs) as models to study diseases and as sources for cell therapy depends on the integrity of their genomes. Despite recent publications of DNA sequence variations in the iPSCs, the true scope of such changes for the entire genome is not clear. Here we report the whole-genome sequencing of three human iPSC lines derived from two cell types of an adult donor by episomal vectors. The vector sequence was undetectable in the deeply sequenced iPSC lines. We identified 1,058-1,808 heterozygous single-nucleotide variants (SNVs), but no copy-number variants, in each iPSC line. Six to twelve of these SNVs were within coding regions in each iPSC line, but 50% of them are synonymous changes and the remaining are not selectively enriched for known genes associated with cancers. Our data thus suggest that episome-mediated reprogramming is not inherently mutagenic during integration-free iPSC induction.
C1 [Cheng, Linzhao; Zou, Chunlin; Chou, Bin-Kuan; Dowey, Sarah N.; Ye, Zhaohui] Johns Hopkins Univ, Inst Cell Engn, Stem Cell Program, Baltimore, MD 21205 USA.
   [Cheng, Linzhao; Zou, Chunlin; Chou, Bin-Kuan; Dowey, Sarah N.; Ye, Zhaohui] Johns Hopkins Univ, Div Hematol, Baltimore, MD 21205 USA.
   [Hansen, Nancy F.; Mullikin, James C.] NHGRI, Comparat Genom Unit, NIH, Bethesda, MD 20892 USA.
   [Zhao, Ling; Liu, P. Paul] NHGRI, Oncogenesis & Dev Sect, NIH, Bethesda, MD 20892 USA.
   [Mullikin, James C.; NISC Comparative Sequencing Progra] NHGRI, NIH Intramural Sequencing Ctr NISC, NIH, Bethesda, MD 20892 USA.
   [Du, Yutao; Zhou, Guangyu; Li, Shijie; Yang, Huanming] Beijing Genom Inst BGI Shenzhen, Shenzhen 518000, Peoples R China.
RP Cheng, LZ (reprint author), Johns Hopkins Univ, Inst Cell Engn, Stem Cell Program, Baltimore, MD 21205 USA.
EM lcheng@welch.jhu.edu; pliu@mail.nih.gov
RI perumal, murugiah/D-1565-2012; Liu, Paul/A-7976-2012; 
OI Liu, Paul/0000-0002-6779-025X; Ye, Zhaohui/0000-0001-5272-9168
FU Johns Hopkins University; NIH [RC2 HL101582, U01 HL099775, R01
   HL073781]; NIH Center for Regenerative Medicine (NCRM); National Human
   Genome Research Institute at NIH
FX We thank Raman Sood and Blake Carrington for PCR and Sanger sequencing
   for confirming mutations and Xianmin Zeng in The Buck Institute in
   California for providing DNA from neural progenitor cells derived from
   BC1 iPSCs. This study was supported in part by Johns Hopkins University
   and NIH grants (RC2 HL101582, U01 HL099775, and R01 HL073781), an award
   from the NIH Center for Regenerative Medicine (NCRM), and The Intramural
   Research Program of The National Human Genome Research Institute at NIH.
NR 25
TC 107
Z9 113
U1 2
U2 13
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1934-5909
J9 CELL STEM CELL
JI Cell Stem Cell
PD MAR 2
PY 2012
VL 10
IS 3
BP 337
EP 344
DI 10.1016/j.stem.2012.01.005
PG 8
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA 908BX
UT WOS:000301466500014
PM 22385660
ER

PT J
AU Bonzo, JA
   Ferry, CH
   Matsubara, T
   Kim, JH
   Gonzalez, FJ
AF Bonzo, Jessica A.
   Ferry, Christina H.
   Matsubara, Tsutomu
   Kim, Jung-Hwan
   Gonzalez, Frank J.
TI Suppression of Hepatocyte Proliferation by Hepatocyte Nuclear Factor 4
   alpha in Adult Mice
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID BONE MORPHOGENETIC PROTEIN-7; HORMONE RECEPTOR SUPERFAMILY;
   HEPATOCELLULAR-CARCINOMA; LIVER-REGENERATION; TRANSCRIPTION FACTOR;
   GENE-EXPRESSION; PROSTATE-CANCER; MOUSE; HNF4-ALPHA; FIBROSIS
AB Hepatocyte nuclear factor 4 alpha (HNF4 alpha) regulates genes involved in lipid and bile acid synthesis, gluconeogenesis, amino acid metabolism, and blood coagulation. In addition to its metabolic role, HNF4 alpha is critical for hepatocyte differentiation, and loss of HNF4 alpha is associated with hepatocellular carcinoma. The hepatocyte-specific Hnf4a knock-out mouse develops severe hepatomegaly and steatosis resulting in premature death, thereby limiting studies of the role of this transcription factor in the adult animal. In addition, gene compensation may complicate analysis of the phenotype of these mice. To overcome these issues, an acute Hnf4a knock-out mouse model was generated through use of the tamoxifen-inducible ErT2cre coupled to the serum albumin gene promoter. Microarray expression analysis revealed up-regulation of genes associated with proliferation and cell cycle control only in the acute liver-specific Hnf4 alpha-null mouse. BrdU and ki67 staining confirmed extensive hepatocyte proliferation in this model. Proliferation was associated with induction of the hepatomitogen Bmp7 as well as reduced basal apoptotic activity. The p53/p63 apoptosis effector gene Perp was further identified as a direct HNF4 alpha target gene. These data suggest that HNF4 alpha maintains hepatocyte differentiation in the adult healthy liver, and its loss may directly contribute to hepatocellular carcinoma development, thus indicating this factor as a possible liver tumor suppressor gene.
C1 [Bonzo, Jessica A.; Ferry, Christina H.; Matsubara, Tsutomu; Kim, Jung-Hwan; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 37,Rm 3106, Bethesda, MD 20892 USA.
EM gonzalef@mail.nih.gov
FU National Cancer Institute, National Institutes of Health (NIH); NIGMS,
   National Institutes of Health; National Institutes of Health Summer
   Internship Program
FX This work was funded by the intramural research program at the National
   Cancer Institute, National Institutes of Health (NIH).; Supported by the
   Pharmacology Research Associate program through NIGMS, National
   Institutes of Health.; Supported by the National Institutes of Health
   Summer Internship Program.
NR 58
TC 48
Z9 48
U1 0
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 MAR 2
PY 2012
VL 287
IS 10
BP 7345
EP 7356
DI 10.1074/jbc.M111.334599
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 902SL
UT WOS:000301060200036
PM 22241473
ER

PT J
AU Xu, X
   Hou, Y
   Yin, XY
   Bao, L
   Tang, AF
   Song, LT
   Li, FQ
   Tsang, S
   Wu, K
   Wu, HJ
   He, WM
   Zeng, L
   Xing, MJ
   Wu, RH
   Jiang, H
   Liu, X
   Cao, DD
   Guo, GW
   Hu, XD
   Gui, YT
   Li, ZS
   Xie, WY
   Sun, XJ
   Shi, M
   Cai, ZM
   Wang, B
   Zhong, MM
   Li, JX
   Lu, ZH
   Gu, N
   Zhang, XQ
   Goodman, L
   Bolund, L
   Wang, J
   Yang, HM
   Kristiansen, K
   Dean, M
   Li, YR
   Wang, J
AF Xu, Xun
   Hou, Yong
   Yin, Xuyang
   Bao, Li
   Tang, Aifa
   Song, Luting
   Li, Fuqiang
   Tsang, Shirley
   Wu, Kui
   Wu, Hanjie
   He, Weiming
   Zeng, Liang
   Xing, Manjie
   Wu, Renhua
   Jiang, Hui
   Liu, Xiao
   Cao, Dandan
   Guo, Guangwu
   Hu, Xueda
   Gui, Yaoting
   Li, Zesong
   Xie, Wenyue
   Sun, Xiaojuan
   Shi, Min
   Cai, Zhiming
   Wang, Bin
   Zhong, Meiming
   Li, Jingxiang
   Lu, Zuhong
   Gu, Ning
   Zhang, Xiuqing
   Goodman, Laurie
   Bolund, Lars
   Wang, Jian
   Yang, Huanming
   Kristiansen, Karsten
   Dean, Michael
   Li, Yingrui
   Wang, Jun
TI Single-Cell Exome Sequencing Reveals Single-Nucleotide Mutation
   Characteristics of a Kidney Tumor
SO CELL
LA English
DT Article
ID MULTIPLE DISPLACEMENT AMPLIFICATION; LUNG-CANCER; SULT1A1 POLYMORPHISM;
   LYSINE ACETYLATION; RENAL-CARCINOMA; HIF PATHWAY; GENOME; GENE;
   EXPRESSION; PROTEIN
AB Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer and has very few mutations that are shared between different patients. To better understand the intratumoral genetics underlying mutations of ccRCC, we carried out single-cell exome sequencing on a ccRCC tumor and its adjacent kidney tissue. Our data indicate that this tumor was unlikely to have resulted from mutations in VHL and PBRM1. Quantitative population genetic analysis indicates that the tumor did not contain any significant clonal subpopulations and also showed that mutations that had different allele frequencies within the population also had different mutation spectrums. Analyses of these data allowed us to delineate a detailed intratumoral genetic landscape at a single-cell level. Our pilot study demonstrates that ccRCC may be more genetically complex than previously thought and provides information that can lead to new ways to investigate individual tumors, with the aim of developing more effective cellular targeted therapies.
C1 [Xu, Xun; Hou, Yong; Yin, Xuyang; Bao, Li; Song, Luting; Li, Fuqiang; Wu, Kui; Wu, Hanjie; He, Weiming; Zeng, Liang; Xing, Manjie; Wu, Renhua; Jiang, Hui; Liu, Xiao; Cao, Dandan; Guo, Guangwu; Hu, Xueda; Wang, Bin; Zhong, Meiming; Li, Jingxiang; Zhang, Xiuqing; Goodman, Laurie; Bolund, Lars; Wang, Jian; Yang, Huanming; Kristiansen, Karsten; Dean, Michael; Li, Yingrui; Wang, Jun] BGI Shenzhen, Shenzhen 518083, Peoples R China.
   [Xu, Xun] BGI Amer, Cambridge, MA 02142 USA.
   [Hou, Yong; Lu, Zuhong; Gu, Ning] Southeast Univ, Sch Biol Sci & Med Engn, Nanjing 210096, Jiangsu, Peoples R China.
   [Hou, Yong; Lu, Zuhong; Gu, Ning] Southeast Univ, State Key Lab Bioelect, Nanjing 210096, Jiangsu, Peoples R China.
   [Tang, Aifa; Li, Zesong; Sun, Xiaojuan; Cai, Zhiming] Shenzhen Second Peoples Hosp, Dept Urol, Shenzhen 518035, Peoples R China.
   [Tang, Aifa; Li, Zesong; Sun, Xiaojuan; Cai, Zhiming] Shenzhen Univ, Inst Urogenital Dis, Shenzhen 518060, Peoples R China.
   [Tsang, Shirley] BioMatrix LLC, Rockville, MD 20849 USA.
   [Wu, Hanjie] S China Univ Technol, Sch Biosci & Biotechnol, Guangzhou 510641, Guangdong, Peoples R China.
   [Xie, Wenyue; Shi, Min; Cai, Zhiming] Peking Univ, Shenzhen PKU HKUST Med Ctr, Inst Urol,Shenzhen Hosp, Guangdong & Shenzhen Key Lab Male Reprod Med & Ge, Shenzhen 518036, Peoples R China.
   [Bolund, Lars] Univ Aarhus, Inst Human Genet, DK-8100 Aarhus, Denmark.
   [Kristiansen, Karsten; Wang, Jun] Univ Copenhagen, Dept Biol, DK-1165 Copenhagen, Denmark.
   [Wang, Jun] Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, DK-1165 Copenhagen, Denmark.
   [Dean, Michael] NCI, Canc & Inflammat Program, NIH, Frederick, MD 21701 USA.
RP Wang, J (reprint author), BGI Shenzhen, Shenzhen 518083, Peoples R China.
EM wangj@genomics.org.cn; deanm@mail.nih.gov; liyr@genomics.org.cn;
   wangj@genomics.org.cn
RI Dean, Michael/G-8172-2012; Lu, Zuhong/A-5448-2013; Li,
   Yingrui/K-1064-2015; Kristiansen, Karsten/J-5148-2014; Wang,
   Jun/C-8434-2016; Wang, Jun/B-9503-2016; 
OI Dean, Michael/0000-0003-2234-0631; Kristiansen,
   Karsten/0000-0002-6024-0917; Wang, Jun/0000-0002-8540-8931; Goodman,
   Laurie/0000-0001-9724-5976; Wang, Jun/0000-0002-2113-5874; Wu,
   Hanjie/0000-0002-5451-4969; hou, yong/0000-0002-0420-0726
FU National Basic Research Program of China (973 program) [2011CB809202,
   2011CB809203]; Chinese 863 program [2009AA022707, 2012AA02A201];
   Shenzhen Municipal Government of China [ZYC201005250020A]; Key
   Laboratory Project, Shenzhen City [CX B200903 110066A,
   CXB201108250096A]; Shenzhen Key Laboratory of Gene Bank for National
   Life Science; Innovative Research Team of Guangdong; Guangdong
   Enterprise Key Laboratory of Human Disease Genomics; Shenzhen Key
   Laboratory, Shenzhen, China [CXB200903090055A, CXB201005250016A]; Danish
   Natural Science Research Council; Danish National Research Foundation;
   National Natural Science Foundation of China; Shenzhen Municipal
   Government; Local Government of Yantian District of Shenzhen; National
   Cancer Institute, National Institutes of Health, USA
FX This work was supported by a National Basic Research Program of China
   (973 program numbers 2011CB809202 and 2011CB809203), the Chinese 863
   program (numbers 2009AA022707 and 2012AA02A201), the Shenzhen Municipal
   Government of China (grant ZYC201005250020A), the Key Laboratory Project
   Supported by Shenzhen City (grants CX B200903 110066A and
   CXB201108250096A), and Shenzhen Key Laboratory of Gene Bank for National
   Life Science. This project was also supported by grants from the
   Innovative Research Team Project of Guangdong, the Guangdong Enterprise
   Key Laboratory of Human Disease Genomics, and the Promotion Program for
   Shenzhen Key Laboratory, Shenzhen, China (CXB200903090055A and
   CXB201005250016A). We also acknowledge the Ole Romer grant from the
   Danish Natural Science Research Council, the Danish National Research
   Foundation, the National Natural Science Foundation of China, and funds
   from the Shenzhen Municipal Government and the Local Government of
   Yantian District of Shenzhen. We also acknowledge support from the
   Intramural Research Program of the National Cancer Institute, National
   Institutes of Health, USA.
NR 55
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U2 134
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PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD MAR 2
PY 2012
VL 148
IS 5
BP 886
EP 895
DI 10.1016/j.cell.2012.02.025
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 901RR
UT WOS:000300985000010
PM 22385958
ER

PT J
AU Kim, JY
   Liu, CY
   Zhang, FY
   Duan, X
   Wen, ZX
   Song, J
   Feighery, E
   Lu, B
   Rujescu, D
   St Clair, D
   Christian, K
   Callicott, JH
   Weinberger, DR
   Song, HJ
   Ming, GL
AF Kim, Ju Young
   Liu, Cindy Y.
   Zhang, Fengyu
   Duan, Xin
   Wen, Zhexing
   Song, Juan
   Feighery, Emer
   Lu, Bai
   Rujescu, Dan
   St Clair, David
   Christian, Kimberly
   Callicott, Joseph H.
   Weinberger, Daniel R.
   Song, Hongjun
   Ming, Guo-Li
TI Interplay between DISC1 and GABA Signaling Regulates Neurogenesis in
   Mice and Risk for Schizophrenia
SO CELL
LA English
DT Article
ID NEWLY GENERATED NEURONS; ADULT BRAIN; GENE-EXPRESSION; MOUSE
   HIPPOCAMPUS; DOWN-REGULATION; STRESS; INTEGRATION; MATURATION; KCC2;
   CELL
AB How extrinsic stimuli and intrinsic factors interact to regulate continuous neurogenesis in the postnatal mammalian brain is unknown. Here we show that regulation of dendritic development of newborn neurons by Disrupted-in-Schizophrenia 1 (DISC1) during adult hippocampal neurogenesis requires neurotransmitter GABA-induced, NKCC1-dependent depolarization through a convergence onto the AKT-mTOR pathway. In contrast, DISC1 fails to modulate early-postnatal hippocampal neurogenesis when conversion of GABA-induced depolarization to hyperpolarization is accelerated. Extending the period of GABA-induced depolarization or maternal deprivation stress restores DISC1-dependent dendritic regulation through mTOR pathway during early-postnatal hippocampal neurogenesis. Furthermore, DISC1 and NKCC1 interact epistatically to affect risk for schizophrenia in two independent case control studies. Our study uncovers an interplay between intrinsic DISC1 and extrinsic GABA signaling, two schizophrenia susceptibility pathways, in controlling neurogenesis and suggests critical roles of developmental tempo and experience in manifesting the impact of susceptibility genes on neuronal development and risk for mental disorders.
C1 [Kim, Ju Young; Liu, Cindy Y.; Duan, Xin; Wen, Zhexing; Song, Juan; Christian, Kimberly; Song, Hongjun; Ming, Guo-Li] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21205 USA.
   [Kim, Ju Young; Liu, Cindy Y.; Wen, Zhexing; Song, Juan; Christian, Kimberly; Song, Hongjun; Ming, Guo-Li] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
   [Zhang, Fengyu; Duan, Xin; Song, Hongjun; Ming, Guo-Li] Johns Hopkins Univ, Sch Med, Solomon Snyder Dept Neurosci, Baltimore, MD 21205 USA.
   [Feighery, Emer; Lu, Bai; Callicott, Joseph H.; Weinberger, Daniel R.] NIMH, Gene Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA.
   [Rujescu, Dan] Univ Munich, Dept Psychiat, D-80336 Munich, Germany.
   [St Clair, David] Univ Aberdeen, Royal Cornhill Hosp, Aberdeen AB25 2ZD, Scotland.
   [Weinberger, Daniel R.; Song, Hongjun] Lieber Inst Brain Dev, Baltimore, MD 21205 USA.
RP Ming, GL (reprint author), Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21205 USA.
EM gming1@jhmi.edu
RI Ming, Guo-li/J-7880-2013; Wen, Zhexing/B-9313-2014; Callicott,
   Joseph/C-9102-2009
OI Callicott, Joseph/0000-0003-1298-3334
FU NIH [NS048271, HD069184, NS047344, MH087874]; MSCRF; NARSAD; IMHRO; NIMH
FX We thank members of Ming and Song Laboratories for help and critical
   comments, L. Liu, Y. Cai, N. Powanpangkul, and Q. Hussaini for technical
   support, and A. Chiang and J. Wang for help with tissue processing. This
   work was supported by the NIH (NS048271 and HD069184), MSCRF, and NARSAD
   to G-l.M., by the NIH (NS047344 and MH087874) and IMHRO to H. S., by the
   NIMH intramural program to D. W., and by postdoctoral fellowships from
   MSCRF to J. Y. K., Z.W., J. S., and K.
NR 51
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U1 1
U2 21
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD MAR 2
PY 2012
VL 148
IS 5
BP 1051
EP 1064
DI 10.1016/j.cell.2011.12.037
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 901RR
UT WOS:000300985000023
PM 22385968
ER

PT J
AU Hakim, O
   Misteli, T
AF Hakim, Ofir
   Misteli, Tom
TI SnapShot: Chromosome Confirmation Capture
SO CELL
LA English
DT Editorial Material
ID CONFORMATION CAPTURE; YEAST GENOME; ORGANIZATION; LOCI
C1 [Hakim, Ofir; Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA.
RP Hakim, O (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
NR 20
TC 10
Z9 10
U1 4
U2 19
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD MAR 2
PY 2012
VL 148
IS 5
BP 1068
EP U245
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 901RR
UT WOS:000300985000027
ER

PT J
AU Richard, SA
   Black, RE
   Checkley, W
AF Richard, Stephanie A.
   Black, Robert E.
   Checkley, William
TI Revisiting the Relationship of Weight and Height in Early Childhood
SO ADVANCES IN NUTRITION
LA English
DT Article; Proceedings Paper
CT Symposium on Building Convergence among Scientific, Programmatic, and
   Policy Communities - Working on Childhood Undernutrition in Developing
   Countries Given at the Annual Experimental Biology Meeting
CY APR 11, 2011
CL Washington, DC
ID HOUSEHOLD FOOD SECURITY; LINEAR GROWTH; RURAL BANGLADESH; PREGNANCY
   OUTCOMES; NUTRITIONAL-STATUS; PHYSICAL GROWTH; NATIONAL-CENTER;
   YOUNG-CHILDREN; UNDERNUTRITION; INTERVENTIONS
AB Ponderal and linear growth of children has been widely studied; however, epidemiologic evidence of a relationship between the two is inconsistent. Child undernutrition in the form of low height for age and low weight for height continues to burden the developing world. A downward shift in the distribution of height for age in the first 2 y of life is commonly observed in many developing countries and is usually summarized as the percentage stunted (height for age Z-score <-2). Similar shifts are seen in weight for height; however, weight-for-height shifts are often less extreme, perhaps because weight for height is more tightly biologically controlled. Low height for age and low weight for height in childhood share some common factors, including food insecurity, infectious diseases, and inappropriate feeding practices. Reductions in weight for height, generally seen as a short-term response to inadequate dietary intake or utilization, are thought to precede decreases in height for age; however, given an adequate diet and no further insults, catch-up linear growth can occur. Serial instances of decreased weight for height, however, are thought to limit the degree of catch-up growth attained, contributing to linear growth retardation. Additional research is needed to identify the factors associated with recovery of linear growth after a child experiences decreased weight for height. Although the direct relationship between weight for height and height for age is likely limited, each of these measurements indicates important information about the general health of children and their risk of the development of illness or dying; therefore, eliminating the downward shift of height for age and weight for height in developing countries should be prioritized as a public policy. Adv. Nutr. 3: 250-254, 2012.
C1 [Richard, Stephanie A.; Black, Robert E.; Checkley, William] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD 21218 USA.
   [Richard, Stephanie A.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Checkley, W (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD 21218 USA.
EM wcheckl1@jhmi.edu
OI Black, Robert/0000-0001-9926-7984
NR 53
TC 10
Z9 10
U1 1
U2 12
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 2161-8313
J9 ADV NUTR
JI Adv. Nutr.
PD MAR
PY 2012
VL 3
IS 2
BP 250
EP 254
DI 10.3945/an.111.001099
PG 5
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 066KO
UT WOS:000313219900018
PM 22516736
ER

PT J
AU Broyles, LM
   Tate, JA
   Happ, MB
AF Broyles, Lauren M.
   Tate, Judith A.
   Happ, Mary Beth
TI USE OF AUGMENTATIVE AND ALTERNATIVE COMMUNICATION STRATEGIES BY FAMILY
   MEMBERS IN THE INTENSIVE CARE UNIT
SO AMERICAN JOURNAL OF CRITICAL CARE
LA English
DT Article
ID POSTTRAUMATIC-STRESS; VENTILATED PATIENTS; CRITICAL ILLNESS;
   DECISION-MAKING; HIGH-RISK; PATIENT; SYMPTOMS; LIFE; ICU; EXPERIENCES
AB Background Little is known about communication between patients and their family members during critical illness and mechanical ventilation in the intensive care unit, including use of augmentative and alternative communication tools and strategies.
   Objectives To identify (1) which augmentative and alternative communication tools families use with nonspeaking intensive care patients and how they are used, and (2) what families and nurses say about communication of family members with nonspeaking intensive care patients.
   Methods A qualitative secondary analysis was conducted of existing data from a clinical trial testing interventions to improve communication between nurses and intensive care patients. Narrative study data (field notes, intervention logs, nurses' interviews) from 127 critically ill adults were reviewed for evidence of family involvement with augmentative and alternative communication tools. Qualitative content analysis was applied for thematic description of family members' and nurses' accounts of patient-family communication.
   Results Family involvement with augmentative and alternative communication tools was evident in 44% of the 93 patients who completed the parent study protocol. Spouses or significant others communicated with patients most often. Main themes describing patient-family communication included (1) families being unprepared and unaware, (2) families' perceptions of communication effectiveness, (3) nurses deferring to or guiding patient-family communication, (4) patients' communication characteristics, and (5) families' experience with and interest in augmentative and alternative communication tools.
   Conclusions Assessment by skilled bedside clinicians can reveal patients' communication potential and facilitate useful augmentative and alternative communication tools and strategies for patients and their families. (American Journal of Critical Care. 2012; 21(2): e21-e32)
C1 [Broyles, Lauren M.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA.
   [Broyles, Lauren M.] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA 15260 USA.
   [Tate, Judith A.] Univ Pittsburgh, Dept Psychiat, NIMH, Pittsburgh, PA 15260 USA.
   [Happ, Mary Beth] Univ Pittsburgh, Dept Acute & Tertiary Care, UPMC Hlth Syst, Sch Nursing,Chair Nursing Sci, Pittsburgh, PA 15260 USA.
RP Broyles, LM (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 7180 Highland Dr,151C-H, Pittsburgh, PA 15206 USA.
EM Lauren.Broyles@va.gov
RI Tate, Judith/C-7447-2015
FU National Institute for Nursing Research [5K24- NR010244]; National
   Institute for Child Health and Human Development [5R01 HD043988]; US
   Department of Veterans Affairs [CDA 10-014]
FX This study was supported by grants (M. Happ, principal investigator)
   from the National Institute for Nursing Research (5K24- NR010244) and
   the National Institute for Child Health and Human Development (5R01
   HD043988). Dr Broyles is currently supported by a Career Development
   Award (CDA 10-014) from the US Department of Veterans Affairs. This
   material is the result of work supported with resources and the use of
   facilities at the VA Pittsburgh Healthcare System, Pittsburgh,
   Pennsylvania. Dr Tate is a National Institute of Mental Health
   postdoctoral research fellow in the clinical research training program
   in geriatric psychiatry at the University of Pittsburgh Department of
   Psychiatry (T32 MH19986, principal investigator, Reynolds).
NR 61
TC 3
Z9 3
U1 2
U2 30
PU AMER ASSOC CRITICAL CARE NURSES
PI ALISO VIEJO
PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA
SN 1062-3264
J9 AM J CRIT CARE
JI Am. J. Crit. Care
PD MAR 1
PY 2012
VL 21
IS 2
BP E21
EP E32
DI 10.4037/ajcc2012752
PG 12
WC Critical Care Medicine; Nursing
SC General & Internal Medicine; Nursing
GA 031LC
UT WOS:000310640300001
PM 22381993
ER

PT J
AU Baroni, M
   Mariani, T
   Elmo, A
   Spagnolo, E
   Cherubini, A
   Maggio, D
   Maggio, M
   Raadicchi, R
   Cepollaro, C
   Lauretani, F
   Bandinelli, S
   Conti, F
   Ferrucci, L
   Ruggiero, C
AF Baroni, M.
   Mariani, T.
   Elmo, A.
   Spagnolo, E.
   Cherubini, A.
   Maggio, D.
   Maggio, M.
   Raadicchi, R.
   Cepollaro, C.
   Lauretani, F.
   Bandinelli, S.
   Conti, F.
   Ferrucci, L.
   Ruggiero, C.
TI THE RELATIONSHIP BETWEEN LEG MUSCLE STRENGHT AND POWER AND PQCT BONE
   MINERAL PARAMETERS IN OLDER PERSONS LIVING IN THE COMMUNITY
SO OSTEOPOROSIS INTERNATIONAL
LA English
DT Meeting Abstract
CT IOF-ECCEO European Congress on Osteoporosis and Osteoarthritis / 2nd
   IOF-ESCEO Pre-Clinical Symposium
CY MAR 21-24, 2012
CL Bordeaux, FRANCE
SP Int Osteoporosis Fdn (IOF), European Soc Clin & Econom Aspects Osteoporosis & Osteoarthritis (ESCEO), Rottapharm, Madaus, Wisepress, Servier Int, Amgen, GlaxoSmithKline (GSK), MSD, B-Cube AG, BeamMed, Danone, Dfine Europe, D3A, Eli Lilly, Expanscience, GE Healthcare, Hologic, IDS, Medi, Medtron, Mindways, Nycomed, Optasia Med, Pfizer Inc
C1 [Baroni, M.; Mariani, T.; Elmo, A.; Spagnolo, E.; Cherubini, A.; Maggio, D.; Raadicchi, R.; Ruggiero, C.] Univ Perugia, Institute Gerontol & Geriatr, Dept Clin & Expt Med, I-06100 Perugia, Italy.
   [Maggio, M.; Lauretani, F.] Univ Parma, Dept Internal Med & Biomed Sci, Sect Geriatr, I-43100 Parma, Italy.
   [Cepollaro, C.] Univ Florence, Dept Internal Med, Florence, Italy.
   [Bandinelli, S.] ASF, Geriatr Unit, Florence, Italy.
   [Ferrucci, L.] NIA, Clin Res Branch, ASTRA Unit, Baltimore, MD 21224 USA.
   [Conti, F.] Univ Roma La Sapienza, Dept Internal Med, Rome, Italy.
NR 2
TC 0
Z9 0
U1 1
U2 3
PU SPRINGER LONDON LTD
PI LONDON
PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND
SN 0937-941X
J9 OSTEOPOROSIS INT
JI Osteoporosis Int.
PD MAR
PY 2012
VL 23
SU 2
BP S367
EP S367
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 012TN
UT WOS:000309259600624
ER

PT J
AU Okano, T
   Kelley, MW
AF Okano, Takayuki
   Kelley, Matthew W.
TI Stem Cell Therapy for the Inner Ear: Recent Advances and Future
   Directions
SO TRENDS IN AMPLIFICATION
LA English
DT Article
DE stem cell therapy; inner ear; hair cell; regeneration
ID HEALTH INTERVIEW SURVEY; VESTIBULAR HAIR-CELLS; SUPPORTING CELLS;
   HEARING IMPAIRMENT; SENSORY EPITHELIA; NEUROTROPHIC FACTOR; MAMMALIAN
   COCHLEA; ACOUSTIC TRAUMA; MOUSE COCHLEA; MICE LACKING
AB In vertebrates, perception of sound, motion, and balance is mediated through mechanosensory hair cells located within the inner ear. In mammals, hair cells are only generated during a short period of embryonic development. As a result, loss of hair cells as a consequence of injury, disease, or genetic mutation, leads to permanent sensory deficits. At present, cochlear implantation is the only option for profound hearing loss. However, outcomes are still variable and even the best implant cannot provide the acuity of a biological ear. The recent emergence of stem cell technology has the potential to open new approaches for hair cell regeneration. The goal of this review is to summarize the current state of inner ear stem cell research from a viewpoint of its clinical application for inner ear disorders to illustrate how complementary studies have the potential to promote and refine stem cell therapies for inner ear diseases. The review initially discusses our current understanding of the genetic pathways that regulate hair cell formation from inner ear progenitors during normal development. Subsequent sections discuss the possible use of endogenous inner ear stem cells to induce repair as well as the initial studies aimed at transplanting stem cells into the ear.
C1 [Kelley, Matthew W.] Natl Inst Deafness & Other Commun Disorders, Lab Cochlear Dev, NIH, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA.
RP Kelley, MW (reprint author), Natl Inst Deafness & Other Commun Disorders, Lab Cochlear Dev, NIH, Porter Neurosci Res Ctr, 35 Convent Dr, Bethesda, MD 20892 USA.
EM Kelleymt@nidcd.nih.gov
FU Intramural Program at the National Institute on Deafness and Other
   Communication Disorders (NIDCD)
FX The authors disclosed receipt of the following financial support for the
   research, authorship, and/or publication of this article: This study was
   supported by funds from the Intramural Program at the National Institute
   on Deafness and Other Communication Disorders (NIDCD).
NR 132
TC 22
Z9 23
U1 1
U2 24
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1084-7138
J9 TRENDS AMPLIF
JI Trends Amplif.
PD MAR
PY 2012
VL 16
IS 1
BP 4
EP 18
DI 10.1177/1084713812440336
PG 15
GA 031ZX
UT WOS:000310682600002
PM 22514095
ER

PT J
AU Srijanto, BR
   Cheney, CP
   Hedden, DL
   Gehl, AC
   Crilly, PB
   Huestis, MA
   Ferrell, TL
AF Srijanto, Bernadeta R.
   Cheney, Christine P.
   Hedden, David L.
   Gehl, Anthony C.
   Crilly, Paul B.
   Huestis, Marilyn A.
   Ferrell, Thomas L.
TI Piezoresistive Microcantilevers-Based Cocaine Biosensors
SO SENSOR LETTERS
LA English
DT Article
DE Cocaine Biosensors; Piezoresistive Microcantilevers;
   Oligonucleotide-Based Aptamers
ID PERFORMANCE LIQUID-CHROMATOGRAPHY; CMOS CHEMICAL MICROSENSORS; WAVE
   IMMUNOASSAY SENSORS; PIEZOELECTRIC IMMUNOSENSOR; VAPOR DETECTION; HUMAN
   HAIR; METABOLITES; APTAMERS; ARRAY; CODEINE
AB An aptamer-coated, piezoresistive, microcantilever-based biosensor has been fabricated and tested as presented here to measure the relative concentration of freebase cocaine in solution. Aptamers were used as the cocaine receptor due to their known high selectivity and affinity for the target molecules in buffered solutions. A Wheatstone bridge composed of four microcantilevers was utilized in converting the biological signal to an electrical signal. The approach here provides a prototype that will lead to a compact and low cost device that will be applicable for in-vivo applications. The performance of this sensor is demonstrated in an in-vitro experiment conducted by flowing a cocaine solution in distilled water over the microcantilever arrays. The response of the device had a limit of detection of 1 ng/ml, which is comparable to the conventional method of cocaine detection in the body performed using gas/liquid chromatography and mass spectrophotometry.
C1 [Srijanto, Bernadeta R.] Univ Tennessee, Dept Elect Engn & Comp Sci, Knoxville, TN 37996 USA.
   [Cheney, Christine P.; Hedden, David L.; Gehl, Anthony C.; Ferrell, Thomas L.] Univ Tennessee, Dept Phys, Knoxville, TN 37996 USA.
   [Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
   [Crilly, Paul B.] US Coast Guard Acad, Dept Engn, Elect Engn Sect, New London, CT 06320 USA.
RP Srijanto, BR (reprint author), Oak Ridge Natl Lab, Ctr Nanophase Mat Sci Div, Oak Ridge, TN 37831 USA.
EM srijantobr@ornl.gov
RI Srijanto, Bernadeta/D-4213-2016; 
OI Srijanto, Bernadeta/0000-0002-1188-1267; Gehl,
   Anthony/0000-0002-4841-403X
FU National Institute on Alcohol Abuse and Alcoholism NIAAA [N01AA23012]
FX This research was supported by the National Institute on Alcohol Abuse
   and Alcoholism NIAAA under Contract No. N01AA23012.
NR 45
TC 9
Z9 9
U1 1
U2 28
PU AMER SCIENTIFIC PUBLISHERS
PI VALENCIA
PA 26650 THE OLD RD, STE 208, VALENCIA, CA 91381-0751 USA
SN 1546-198X
J9 SENSOR LETT
JI Sens. Lett.
PD MAR-APR
PY 2012
VL 10
IS 3-4
BP 850
EP 855
DI 10.1166/sl.2012.2335
PG 6
WC Chemistry, Analytical; Electrochemistry; Instruments & Instrumentation;
   Physics, Applied
SC Chemistry; Electrochemistry; Instruments & Instrumentation; Physics
GA 009IE
UT WOS:000309018700025
ER

PT J
AU Zhang, ZW
   Albert, PS
   Simons-Morton, B
AF Zhang, Zhiwei
   Albert, Paul S.
   Simons-Morton, Bruce
TI MARGINAL ANALYSIS OF LONGITUDINAL COUNT DATA IN LONG SEQUENCES: METHODS
   AND APPLICATIONS TO A DRIVING STUDY
SO ANNALS OF APPLIED STATISTICS
LA English
DT Article
DE Correlation; generalized estimating equation; multiple outputation;
   overdispersion; random effect; separated blocks; within-cluster
   resampling
ID ESTIMATING EQUATIONS; REGRESSION-MODEL; TIME-SERIES; BINARY DATA;
   JACKKNIFE; VARIANCE
AB Most of the available methods for longitudinal data analysis are designed and validated for the situation where the number of subjects is large and the number of observations per subject is relatively small. Motivated by the Naturalistic Teenage Driving Study (NTDS), which represents the exact opposite situation, we examine standard and propose new methodology for marginal analysis of longitudinal count data in a small number of very long sequences. We consider standard methods based on generalized estimating equations, under working independence or an appropriate correlation structure, and find them unsatisfactory for dealing with time-dependent covariates when the counts are low. For this situation, we explore a within-cluster resampling (WCR) approach that involves repeated analyses of random subsamples with a final analysis that synthesizes results across subsamples. This leads to a novel WCR method which operates on separated blocks within subjects and which performs better than all of the previously considered methods. The methods are applied to the NTDS data and evaluated in simulation experiments mimicking the NTDS.
C1 [Zhang, Zhiwei] US FDA, Div Biostat, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
   [Albert, Paul S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA.
   [Simons-Morton, Bruce] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA.
RP Zhang, ZW (reprint author), US FDA, Div Biostat, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM zhiwei.zhang@fda.hhs.gov; albertp@mail.nih.gov; mortonb@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health (NIH),
   Eunice Kennedy Shriver National Institute of Child Health and Human
   Development
FX Supported by the Intramural Research Program of the National Institutes
   of Health (NIH), Eunice Kennedy Shriver National Institute of Child
   Health and Human Development. The computation was facilitated by the
   Biowulf cluster computer system made available by the Center for
   Information-Technology at the NIH.
NR 24
TC 2
Z9 2
U1 2
U2 8
PU INST MATHEMATICAL STATISTICS
PI CLEVELAND
PA 3163 SOMERSET DR, CLEVELAND, OH 44122 USA
SN 1932-6157
J9 ANN APPL STAT
JI Ann. Appl. Stat.
PD MAR
PY 2012
VL 6
IS 1
BP 27
EP 54
DI 10.1214/11-AOAS507
PG 28
WC Statistics & Probability
SC Mathematics
GA 991QJ
UT WOS:000307716000002
PM 27087885
ER

PT J
AU Klee, MM
AF Klee, Maurice M.
TI The Inventor Who Got More Than He Asked For
SO IEEE PULSE
LA English
DT Editorial Material
C1 [Klee, Maurice M.] Michigan State Univ, Coll Engn, E Lansing, MI 48824 USA.
   [Klee, Maurice M.] NIH, Bethesda, MD 20892 USA.
EM mk@maurieklee.com
NR 0
TC 0
Z9 0
U1 0
U2 0
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 2154-2287
J9 IEEE PULSE
JI IEEE Pulse
PD MAR-APR
PY 2012
VL 3
IS 2
BP 78
EP 78
DI 10.1109/MPUL.2012.2184459
PG 1
WC Engineering, Biomedical
SC Engineering
GA 992UY
UT WOS:000307806600019
ER

PT J
AU Shukan, ET
   Boe, CY
   Hasenfus, AV
   Pieper, BA
   Snowdon, CT
AF Shukan, Evan T.
   Boe, Carla Y.
   Hasenfus, Aimee V.
   Pieper, Bridget A.
   Snowdon, Charles T.
TI Normal Hematologic and Serum Biochemical Values of Cotton-Top Tamarins
   (Saguinus oedipus)
SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE
LA English
DT Article
ID INFLAMMATORY-BOWEL-DISEASE; MARROW-CHIMERIC PRIMATE; MONKEYS
   MACACA-MULATTA; NEW-WORLD PRIMATE; COLON-CANCER; CAPTIVE CHIMPANZEES;
   CLINICAL-CHEMISTRY; SOCIAL-ENVIRONMENT; PAN-TROGLODYTES; BLOOD-CHEMISTRY
AB We obtained whole-blood hematologic and serum biochemical values from 38 captive-bred cotton-top tamarins (Saguinus oedipus). Data were analyzed to determine the effect of sex on blood parameters. Significant differences between either the means or medians of male and female tamarins were found for creatinine, hematocrit, hemoglobin, RBC count, and PCV. These results establish baseline hematologic and serum biochemical values and provide a useful resource not previously available in the peer-reviewed literature for the clinical care of cotton-top tamarins, a critically endangered New World primate, in a captive setting.
C1 [Shukan, Evan T.] NINDS, NIH, Anim Hlth Care Sect, Bethesda, MD 20892 USA.
   [Boe, Carla Y.; Hasenfus, Aimee V.; Pieper, Bridget A.; Snowdon, Charles T.] Univ Wisconsin, Dept Psychol, Madison, WI 53706 USA.
RP Shukan, ET (reprint author), NINDS, NIH, Anim Hlth Care Sect, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM shukanet@mail.nih.gov
FU National Institute of Mental Health [MH029775, MH035215]; NIH, NINDS
FX Support for this project and for the housing of these animals as part of
   other research protocols came from National Institute of Mental Health
   grants MH029775 and MH035215 and from the Dean of the College of Letters
   and Science. We also acknowledge Dr Sungyoung Auh (Office of the
   Clinical Director, NINDS, NIH) for her assistance with statistical
   analysis. This research was supported in part by the Intramural Research
   Program of the NIH, NINDS.
NR 60
TC 2
Z9 2
U1 1
U2 4
PU AMER ASSOC LABORATORY ANIMAL SCIENCE
PI MEMPHIS
PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA
SN 1559-6109
J9 J AM ASSOC LAB ANIM
JI J. Amer. Assoc. Lab. Anim. Sci.
PD MAR
PY 2012
VL 51
IS 2
BP 150
EP 154
PG 5
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 978UV
UT WOS:000306772200002
PM 22776113
ER

PT J
AU Kilimnik, G
   Jo, J
   Periwal, V
   Zielinski, MC
   Hara, M
AF Kilimnik, German
   Jo, Junghyo
   Periwal, Vipul
   Zielinski, Mark C.
   Hara, Manami
TI Quantification of islet size and architecture
SO ISLETS
LA English
DT Article
DE islet; islet size; islet architecture; pancreas; diabetes
AB Human islets exhibit distinct islet architecture particularly in large islets that comprise of a relatively abundant fraction of alpha-cells intermingled with beta-cells, whereas mouse islets show largely similar architecture of a beta-cell core with alpha-cells in the periphery. In humans, islet architecture is islet-size dependent. Changes in endocrine cell mass preferentially occurred in large islets as demonstrated in our recent study on pathological changes of the pancreas in patients with type 2 diabetes. 1 The size dependency of human islets in morphological changes prompted us to develop a method to capture the representative islet distribution in the whole pancreas section combined with a semi-automated analysis to quantify changes in islet architecture. The computer-assisted quantification allows detailed examination of endocrine cell composition in individual islets and minimizes sampling bias. The standard immunohistochemistry based method is widely applicable to various specimens, which is particularly useful for large animal studies but is also applied to a large-scale analysis of the whole organ section from mice. In this article, we describe the method of image capture, parameters measured, data analysis and interpretation of the data.
C1 [Kilimnik, German; Zielinski, Mark C.; Hara, Manami] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
   [Jo, Junghyo; Periwal, Vipul] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD USA.
RP Hara, M (reprint author), Univ Chicago, Dept Med, 5841 S Maryland Ave, Chicago, IL 60637 USA.
EM mhara@midway.uchicago.edu
RI Periwal, Vipul/I-1728-2012; Jo, Junghyo/D-4889-2011; 
OI Zielinski, Mark/0000-0002-6950-6689
FU US Public Health Service [DK-081527, DK-042086, DK-20595, DK-072473];
   NIH, NIDDK
FX The study is supported by US Public Health Service Grant DK-081527,
   DK-042086 and DK-20595 to the University of Chicago Diabetes Research
   and Training Center (Animal Models Core), DK-072473, and a gift from the
   Kovler Family Foundation (M.H.); and the intramural research program of
   the NIH, NIDDK (J.J. and V.P.). The funders had no role in study design,
   data collection and analysis, decision to publish, or preparation of the
   manuscript.
NR 10
TC 21
Z9 21
U1 0
U2 3
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1938-2014
J9 ISLETS
JI Islets
PD MAR-APR
PY 2012
VL 4
IS 2
BP 167
EP 172
DI 10.4161/isl.19256
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 961MY
UT WOS:000305469800011
PM 22653677
ER

PT J
AU Uhlemann, AC
   Porcella, SF
   Trivedi, S
   Sullivan, SB
   Hafer, C
   Kennedy, AD
   Barbian, KD
   McCarthy, AJ
   Street, C
   Hirschberg, DL
   Lipkin, WI
   Lindsay, JA
   DeLeo, FR
   Lowy, FD
AF Uhlemann, Anne-Catrin
   Porcella, Stephen F.
   Trivedi, Sheetal
   Sullivan, Sean B.
   Hafer, Cory
   Kennedy, Adam D.
   Barbian, Kent D.
   McCarthy, Alex J.
   Street, Craig
   Hirschberg, David L.
   Lipkin, W. Ian
   Lindsay, Jodi A.
   DeLeo, Frank R.
   Lowy, Franklin D.
TI Identification of a Highly Transmissible Animal-Independent
   Staphylococcus aureus ST398 Clone with Distinct Genomic and Cell
   Adhesion Properties
SO MBIO
LA English
DT Article
ID METHICILLIN-RESISTANT; PIG FARMERS; MRSA CC398; HOST; HUMANS; SEQUENCE;
   STRAIN; COLONIZATION; ADAPTATION; POULTRY
AB A methicillin-resistant Staphylococcus aureus (MRSA) clone known as ST398 has emerged as a major cause of acute infections in individuals who have close contact with livestock. More recently, the emergence of an animal-independent ST398 methicillin-sensitive S. aureus (MSSA) clone has been documented in several countries. However, the limited surveillance of MSSA has precluded an accurate assessment of the global spread of ST398 and its clinical relevance. Here we provide evidence that ST398 is a frequent source of MSSA infections in northern Manhattan and is readily transmitted between individuals in households. This contrasts with the limited transmissibility of livestock-associated ST398 (LA-ST398) MRSA strains between humans. Our whole-genome sequence analysis revealed that the chromosome of the human-associated ST398 MSSA clone is smaller than that of the LA-ST398 MRSA reference strain S0385, due mainly to fewer mobile genetic elements (MGEs). In contrast, human ST398 MSSA isolates harbored the prophage phi 3 and the human-specific immune evasion cluster (IEC) genes chp and scn. While most of the core genome was conserved between the human ST398 MSSA clone and S0385, these strains differed substantially in their repertoire and composition of intact adhesion genes. These genetic changes were associated with significantly enhanced adhesion of human ST398 MSSA isolates to human skin keratinocytes and keratin. We propose that the human ST398 MSSA clone can spread independent of animal contact using an optimized repertoire of MGEs and adhesion molecules adapted to transmission among humans.
   IMPORTANCE Staphylococcus aureus strains have generally been considered to be species specific. However, cross-species transfers of S. aureus clones, such as ST398 methicillin-resistant S. aureus (MRSA), from swine to humans have been reported. Recently, we observed the emergence of ST398 methicillin-susceptible S. aureus (MSSA) as a colonizing strain of humans in northern Manhattan. Here we report that ST398 is a frequent cause of MSSA infections in this urban setting. The ST398 MSSA clone was readily transmitted within households, independent of animal contact. We discovered that human ST398 MSSA genomes were smaller than that of the LA-ST398 strain S0385 due to fewer mobile genetic elements. Human and LA-ST398 strains also differed in their composition of adhesion genes and their ability to bind to human skin keratinocytes, providing a potential mechanism of S. aureus host adaptation. Our findings illustrate the importance of implementing molecular surveillance of MSSA given the evidence for the rapid and clinically undetected spread of ST398 MSSA.
C1 [Uhlemann, Anne-Catrin; Trivedi, Sheetal; Sullivan, Sean B.; Hafer, Cory; Lowy, Franklin D.] Columbia Univ, Coll Phys & Surg, Div Infect Dis, Dept Med, New York, NY 10027 USA.
   [Porcella, Stephen F.; Barbian, Kent D.] NIAID, Genom Unit, Res Technol Sect, Rocky Mt Labs,NIH, Hamilton, MT USA.
   [Kennedy, Adam D.; DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT USA.
   [McCarthy, Alex J.; Lindsay, Jodi A.] Univ London, Div Clin Sci, Ctr Infect, London, England.
   [Street, Craig; Hirschberg, David L.; Lipkin, W. Ian] Columbia Univ, Ctr Infect & Immun, Mailman Sch Publ Hlth, New York, NY USA.
RP Uhlemann, AC (reprint author), Columbia Univ, Coll Phys & Surg, Div Infect Dis, Dept Med, New York, NY 10027 USA.
EM au2110@columbia.edu
RI Lindsay, Jodi/B-9565-2008; 
OI Lindsay, Jodi/0000-0002-5219-1625; DeLeo, Frank/0000-0003-3150-2516
FU Intramural Research Program of the National Institute of Allergy and
   Infectious Diseases, NIH; NIH [K08 AI090013, R01 AI077690, R01
   AI077690-S1, AI057158]; Defense Threat Reduction Agency
FX This research was supported in part by the Intramural Research Program
   of the National Institute of Allergy and Infectious Diseases, NIH, and
   by NIH funding to A.-C.U. (K08 AI090013), F.D.L. (R01 AI077690 and R01
   AI077690-S1), and W.I.L. (AI057158) and the Defense Threat Reduction
   Agency.
NR 40
TC 36
Z9 36
U1 2
U2 13
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD MAR-APR
PY 2012
VL 3
IS 2
AR e00027-12
DI 10.1128/mBio.00027-12
PG 9
WC Microbiology
SC Microbiology
GA 959FA
UT WOS:000305297100005
ER

PT J
AU Myles, IA
   Datta, SK
AF Myles, Ian A.
   Datta, Sandip K.
TI Staphylococcus aureus: an introduction
SO SEMINARS IN IMMUNOPATHOLOGY
LA English
DT Editorial Material
ID CHRONIC MUCOCUTANEOUS CANDIDIASIS; SOFT-TISSUE INFECTIONS; HYPER-IGE
   SYNDROME; PROTEIN-A; METHICILLIN-RESISTANCE; BACTERIAL-INFECTIONS;
   ATOPIC-DERMATITIS; ALPHA-HEMOLYSIN; CLUMPING FACTOR; ENTEROTOXIN-B
C1 [Myles, Ian A.; Datta, Sandip K.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Datta, SK (reprint author), NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM dattas@niaid.nih.gov
OI Datta, Sandip/0000-0003-0243-7815
FU Intramural NIH HHS [ZIA AI001043-04]
NR 71
TC 6
Z9 6
U1 0
U2 9
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1863-2297
J9 SEMIN IMMUNOPATHOL
JI Semin. Immunopathol.
PD MAR
PY 2012
VL 34
IS 2
BP 181
EP 184
DI 10.1007/s00281-011-0301-9
PG 4
WC Immunology; Pathology
SC Immunology; Pathology
GA 958JR
UT WOS:000305233300001
PM 22282052
ER

PT J
AU Otto, M
AF Otto, Michael
TI Molecular basis of Staphylococcus epidermidis infections
SO SEMINARS IN IMMUNOPATHOLOGY
LA English
DT Review
DE Staphylococcus epidermidis; Biofilm; Phenol-soluble modulins;
   Polysaccharide intercellular adhesin; Device-related infections;
   Hospital-associated infections
ID POLYSACCHARIDE INTERCELLULAR ADHESIN; ACCUMULATION-ASSOCIATED PROTEIN;
   CATHETER-ASSOCIATED INFECTION; AUREUS NASAL COLONIZATION; HORIZONTAL
   GENE-TRANSFER; PHENOL-SOLUBLE MODULINS; SEQUENCE ELEMENT IS256;
   PEPTIDE-SENSING SYSTEM; WALL TEICHOIC-ACIDS; BIOFILM FORMATION
AB Staphylococcus epidermidis is the most important member of the coagulase-negative staphylococci and one of the most abundant colonizers of human skin. While for a long time regarded as innocuous, it has been identified as the most frequent cause of device-related infections occurring in the hospital setting and is therefore now recognized as an important opportunistic pathogen. S. epidermidis produces a series of molecules that provide protection from host defenses. Specifically, many proteins and exopolymers, such as the exopolysaccharide PIA, contribute to biofilm formation and inhibit phagocytosis and the activity of human antimicrobial peptides. Furthermore, recent research has identified a family of pro-inflammatory peptides in S. epidermidis, the phenol-soluble modulins (PSMs), which have multiple functions in immune evasion and biofilm development, and may be cytolytic. However, in accordance with the relatively benign relationship that S. epidermidis has with its host, production of aggressive members of the PSM family is kept at a low level. Interestingly, in contrast to S. aureus with its large arsenal of toxins developed for causing infection in the human host, most if not all "virulence factors" of S. epidermidis appear to have original functions in the commensal lifestyle of this bacterium.
C1 NIAID, Pathogen Mol Genet Sect, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA.
RP Otto, M (reprint author), NIAID, Pathogen Mol Genet Sect, Lab Human Bacterial Pathogenesis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM motto@niaid.nih.gov
OI Otto, Michael/0000-0002-2222-4115
FU National Institute of Allergy and Infectious Diseases, National
   Institutes of Health
FX This work was supported by the Intramural Research Program of the
   National Institute of Allergy and Infectious Diseases, National
   Institutes of Health.
NR 138
TC 73
Z9 80
U1 1
U2 40
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1863-2297
J9 SEMIN IMMUNOPATHOL
JI Semin. Immunopathol.
PD MAR
PY 2012
VL 34
IS 2
BP 201
EP 214
DI 10.1007/s00281-011-0296-2
PG 14
WC Immunology; Pathology
SC Immunology; Pathology
GA 958JR
UT WOS:000305233300003
PM 22095240
ER

PT J
AU Rigby, KM
   DeLeo, FR
AF Rigby, Kevin M.
   DeLeo, Frank R.
TI Neutrophils in innate host defense against Staphylococcus aureus
   infections
SO SEMINARS IN IMMUNOPATHOLOGY
LA English
DT Review
DE Staphylococcus aureus; MRSA; Neutrophil; Immune evasion
ID PANTON-VALENTINE LEUKOCIDIN; HUMAN POLYMORPHONUCLEAR LEUKOCYTES;
   PROGRAMMED CELL-DEATH; COMMUNITY-ACQUIRED PNEUMONIA; PHAGOCYTE NADPH
   OXIDASE; APOPTOSIS DIFFERENTIATION PROGRAM; CHRONIC
   GRANULOMATOUS-DISEASE; SUPEROXIDE ANION GENERATION; RESPIRATORY BURST
   OXIDASE; CATABOLIC MOBILE ELEMENT
AB Staphylococcus aureus has been an important human pathogen throughout history and is currently a leading cause of bacterial infections worldwide. S. aureus has the unique ability to cause a continuum of diseases, ranging from minor skin infections to fatal necrotizing pneumonia. Moreover, the emergence of highly virulent, drug-resistant strains such as methicillin-resistant S. aureus in both healthcare and community settings is a major therapeutic concern. Neutrophils are the most prominent cellular component of the innate immune system and provide an essential primary defense against bacterial pathogens such as S. aureus. Neutrophils are rapidly recruited to sites of infection where they bind and ingest invading S. aureus, and this process triggers potent oxidative and non-oxidative antimicrobial killing mechanisms that serve to limit pathogen survival and dissemination. S. aureus has evolved numerous mechanisms to evade host defense strategies employed by neutrophils, including the ability to modulate normal neutrophil turnover, a process critical to the resolution of acute inflammation. Here we provide an overview of the role of neutrophils in host defense against bacterial pathogens and discuss strategies employed by S. aureus to circumvent neutrophil function.
C1 [Rigby, Kevin M.; DeLeo, Frank R.] NIAID, Lab Human Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP DeLeo, FR (reprint author), NIAID, Lab Human Pathogenesis, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA.
EM fdeleo@niaid.nih.gov
OI DeLeo, Frank/0000-0003-3150-2516
FU National Institute of Allergy and Infectious Diseases, National
   Institutes of Health
FX The authors are supported by the Intramural Research Program of the
   National Institute of Allergy and Infectious Diseases, National
   Institutes of Health.
NR 299
TC 120
Z9 121
U1 2
U2 32
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1863-2297
J9 SEMIN IMMUNOPATHOL
JI Semin. Immunopathol.
PD MAR
PY 2012
VL 34
IS 2
BP 237
EP 259
DI 10.1007/s00281-011-0295-3
PG 23
WC Immunology; Pathology
SC Immunology; Pathology
GA 958JR
UT WOS:000305233300005
PM 22080185
ER

PT J
AU Wei, LY
   Wu, JH
   Li, GQ
   Shi, N
AF Wei, Linyi
   Wu, Jiuhong
   Li, Guanqun
   Shi, Ning
TI Cis-enone Resorcylic Acid Lactones (RALs) as Irreversible Protein Kinase
   Inhibitors
SO CURRENT PHARMACEUTICAL DESIGN
LA English
DT Review
DE Resorcylic acid lactones (RALs); irreversible protein kinase; MAPK
   kinases
ID GROWTH-FACTOR RECEPTOR; SIGNALING PATHWAY; KAPPA-B; CASCADE; DESIGN;
   DRUG; TAK1; CANCER; POTENT; EGFR
AB Resorcylic acid lactones (RALs) constitute a group of polyketide natural products with a large macrocyclic ring fused to resorcylic acid. Despite distinct core scaffold from all marketed kinase inhibitors, RALs bearing a cis-enone moiety have recently shown irreversible yet selective inhibition on a subset of kinases along the MAPK signaling pathway such as MEK, ERK and TAK1. The biochemical and structural studies have demonstrated that the cis-enone RALs can inhibit kinase activity by forming a covalent Michael adduct with an adequately positioned cysteine residue in the ATP binding pocket. This review discusses the mechanism of action, synthetic strategies, and structure-activity relationships (SARs) of cis-enone RALs. It is anticipated that design, synthesis and evaluation of cis-enone RALs analogs will diversify the chemical space of kinase inhibitors and facilitate the development of new leads for the treatment of various diseases such as cancer and inflammatory disorders.
C1 [Wei, Linyi] NCI Frederick, Lab Synthet Chem, SAIC Frederick Inc, Frederick, MD 21702 USA.
   [Wu, Jiuhong; Shi, Ning] No 306 Hosp, Dept Pharm, Beijing 100101, Peoples R China.
   [Li, Guanqun] Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA.
RP Wei, LY (reprint author), NCI Frederick, Lab Synthet Chem, SAIC Frederick Inc, Bldg 322,Rm 102, Frederick, MD 21702 USA.
EM weil3@mail.nih.gov
NR 54
TC 6
Z9 6
U1 0
U2 16
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
   EMIRATES
SN 1381-6128
J9 CURR PHARM DESIGN
JI Curr. Pharm. Design
PD MAR
PY 2012
VL 18
IS 9
BP 1186
EP 1198
PG 13
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 950US
UT WOS:000304676300003
PM 22316158
ER

PT J
AU Bienstock, RJ
AF Bienstock, Rachelle J.
TI Computational Drug Design Targeting Protein-Protein Interactions
SO CURRENT PHARMACEUTICAL DESIGN
LA English
DT Review
DE Protein-protein interactions; fragment-based ligand design;
   protein-protein inhibitors; computational drug design; structure-based
   ligand design; protein-interface hot-spots
ID SMALL-MOLECULE INHIBITORS; IMMUNODEFICIENCY-VIRUS TYPE-1;
   STRUCTURE-BASED DISCOVERY; REVERSE-TRANSCRIPTASE DIMER; P-ARYLTHIO
   CINNAMIDES; NITRIC-OXIDE SYNTHASE; DRUGGABLE HOT-SPOTS; NERVE
   GROWTH-FACTOR; CRYSTAL-STRUCTURE; WEB SERVER
AB Novel discoveries in molecular disease pathways within the cell, combined with increasing information regarding protein binding partners has lead to a new approach in drug discovery. There is interest in designing drugs to modulate protein-protein interactions as opposed to solely targeting the catalytic active site within a single enzyme or protein. There are many challenges in this new approach to drug discovery, particularly since the protein-protein interface has a larger surface area, can comprise a discontinuous epitope, and is more amorphous and less well defined than the typical drug design target, a small contained enzyme-binding pocket. Computational methods to predict modes of protein-protein interaction, as well as protein interface hot spots, have garnered significant interest, in order to facilitate the development of drugs to successfully disrupt and inhibit protein-protein interactions. This review summarizes some current methods available for computational protein-protein docking, as well as tabulating some examples of the successful design of antagonists and small molecule inhibitors for protein-protein interactions. Several of these drugs are now beginning to appear in the clinic.
C1 NIEHS, Res Triangle Pk, NC 27709 USA.
RP Bienstock, RJ (reprint author), NIEHS, POB 12233,MD F0-011, Res Triangle Pk, NC 27709 USA.
EM biensto1@niehs.nih.gov
NR 165
TC 33
Z9 33
U1 4
U2 60
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
   EMIRATES
SN 1381-6128
J9 CURR PHARM DESIGN
JI Curr. Pharm. Design
PD MAR
PY 2012
VL 18
IS 9
BP 1240
EP 1254
PG 15
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 950US
UT WOS:000304676300006
PM 22316151
ER

PT J
AU Nussinov, R
   Tsai, CJ
AF Nussinov, Ruth
   Tsai, Chung-Jung
TI The Different Ways through Which Specificity Works in Orthosteric and
   Allosteric Drugs
SO CURRENT PHARMACEUTICAL DESIGN
LA English
DT Review
DE Allostery; allosteric drug design; allosteric drug development;
   allosteric drug specificity; cellular network; pathways; affinity;
   concentration; dynamic landscape
ID ENERGY LANDSCAPES; BINDING CASCADES; RECEPTORS; PROTEIN; PRINCIPLES;
   DISCOVERY; DESIGN; MODULATORS; RECOGNITION; ACTIVATION
AB Currently, there are two types of drugs on the market: orthosteric, which bind at the active site; and allosteric, which bind elsewhere on the protein surface, and allosterically change the conformation of the protein binding site. In this perspective we argue that the different mechanisms through which the two drug types affect protein activity and their potential pitfalls call for different considerations in drug design. The key problem facing orthosteric drugs is side effects which can occur by drug binding to homologous proteins sharing a similar binding site. Hence, orthosteric drugs should have very high affinity to the target; this would allow a low dosage to selectively achieve the goal of target-only binding. By contrast, allosteric drugs work by shifting the free energy landscape. Their binding to the protein surface perturbs the protein surface atoms, and the perturbation propagates like waves, finally reaching the binding site. Effective drugs should have atoms in good contact with the 'right' protein atoms; that is, the contacts should elicit propagation waves optimally reaching the protein binding site target. While affinity is important, the design should consider the protein conformational ensemble and the preferred propagation states. We provide examples from functional in vivo scenarios for both types of cases, and suggest how high potency can be achieved in allosteric drug development.
C1 [Nussinov, Ruth; Tsai, Chung-Jung] NCI Frederick, Ctr Canc Res Nanobiol Program, SAIC Frederick Inc, Basic Res Program, Ft Detrick, MD 21702 USA.
   [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel.
RP Nussinov, R (reprint author), NCI Frederick, Ctr Canc Res Nanobiol Program, SAIC Frederick Inc, Basic Res Program, Bldg 469,Rm 151, Ft Detrick, MD 21702 USA.
EM ruthnu@helix.nih.gov
FU National Cancer Institute, National Institutes of Health
   [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer
   Research
FX This project has been funded in whole or in part with Federal funds from
   the National Cancer Institute, National Institutes of Health, under
   contract number HHSN261200800001E. The content of this publication does
   not necessarily reflect the views or policies of the Department of
   Health and Human Services, nor does mention of trade names, commercial
   products, or organizations imply endorsement by the U. S. Government.
   This research was supported (in part) by the Intramural Research Program
   of the NIH, National Cancer Institute, Center for Cancer Research.
NR 58
TC 31
Z9 32
U1 0
U2 15
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
   EMIRATES
SN 1381-6128
J9 CURR PHARM DESIGN
JI Curr. Pharm. Design
PD MAR
PY 2012
VL 18
IS 9
BP 1311
EP 1316
PG 6
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 950US
UT WOS:000304676300010
PM 22316155
ER

PT J
AU Hu, ZH
   Follmann, DA
   Qin, J
AF Hu, Zonghui
   Follmann, Dean A.
   Qin, Jing
TI Semiparametric Double Balancing Score Estimation for Incomplete Data
   With Ignorable Missingness
SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
LA English
DT Article
DE Doubly robust; Nonparametric kernel regression; Propensity score
ID PROPENSITY SCORE; KERNEL REGRESSION; MODELS; CONSISTENCY
AB When estimating the marginal mean response with missing observations, a critical issue is robustness to model misspecification. In this article, we propose a semiparametric estimation method with extended double robustness that attains the optimal efficiency under less stringent requirement for model specifications than the doubly robust estimators. In this semiparametric estimation, covariate information is collapsed into a two-dimensional score S. with one dimension for (i) the pattern of missingness and the other for (ii) the pattern of response, both estimated from some working parametric models. The mean response E(Y) is then estimated by the sample mean of E(Y vertical bar S), which is estimated via nonparametric regression. The semiparametric estimator is consistent if either the "core" of (i) or the "core" of (ii) is captured by S, and attains the optimal efficiency if both are captured by S. As the "cores" can be obtained without correctly specifying the full parametric models for (i) or (ii), the proposed estimator can be more robust than other doubly robust estimators. As S contains the propensity score as one component, the proposed estimator avoids the use and the shortcomings of inverse propensity weighting. This semiparametric estimator is most appealing for high-dimensional covariates, where fully correct model specification is challenging and nonparametric estimation is not feasible due to the problem of dimensionality. Numerical performance is investigated by simulation studies.
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
NR 29
TC 2
Z9 2
U1 0
U2 3
PU AMER STATISTICAL ASSOC
PI ALEXANDRIA
PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA
SN 0162-1459
EI 1537-274X
J9 J AM STAT ASSOC
JI J. Am. Stat. Assoc.
PD MAR
PY 2012
VL 107
IS 497
BP 247
EP 257
DI 10.1080/01621459.2012.656009
PG 11
WC Statistics & Probability
SC Mathematics
GA 951QN
UT WOS:000304735200020
ER

PT J
AU Hein, AM
   O'Banion, MK
AF Hein, Amy M.
   O'Banion, M. Kerry
TI Neuroinflammation and Cognitive Dysfunction in Chronic Disease and Aging
SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY
LA English
DT Editorial Material
ID ALZHEIMERS-DISEASE; AGED MICE; BRAIN; NEURODEGENERATION; MEMORY
C1 [Hein, Amy M.; O'Banion, M. Kerry] Univ Rochester, Sch Med & Dent, Dept Neurobiol & Anat, Rochester, NY 14642 USA.
   [Hein, Amy M.] Natl Inst Neurol Disorders & Stroke, Amer Assoc Adv Sci, Amer Psychol Assoc Execut Branch, Washington, DC USA.
RP O'Banion, MK (reprint author), Univ Rochester, Sch Med & Dent, Dept Neurobiol & Anat, 601 Elmwood Ave,Box 603, Rochester, NY 14642 USA.
EM kerry_obanion@urmc.rochester.edu
FU NIA NIH HHS [R01 AG03149]; NIAID NIH HHS [U19AI091036]; NIDA NIH HHS
   [R01DA026009]; NINDS NIH HHS [T32 NS051152]
NR 24
TC 5
Z9 6
U1 0
U2 1
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 MAR
PY 2012
VL 7
IS 1
SI SI
BP 3
EP 6
DI 10.1007/s11481-011-9340-1
PG 4
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 943YM
UT WOS:000304164000002
PM 22252623
ER

PT J
AU Hein, AM
   Zarcone, TJ
   Parfitt, DB
   Matousek, SB
   Carbonari, DM
   Olschowka, JA
   O'Banion, MK
AF Hein, Amy M.
   Zarcone, Troy J.
   Parfitt, David B.
   Matousek, Sarah B.
   Carbonari, Dena M.
   Olschowka, John A.
   O'Banion, M. Kerry
TI Behavioral, Structural and Molecular Changes following Long-term
   Hippocampal IL-1 beta Overexpression in Transgenic Mice
SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY
LA English
DT Article
DE Interleukin-1 beta; Hippocampus; Neuroinflammation; Learning; Memory;
   Sickness behavior
ID FOOD-MOTIVATED BEHAVIOR; INTERLEUKIN-1-BETA EXPRESSION; CHRONIC
   NEUROINFLAMMATION; COGNITIVE IMPAIRMENT; DORSAL-HIPPOCAMPUS; STROKE
   PATIENTS; BRAIN-INJURY; RATS; INFLAMMATION; DISEASE
AB Chronic neuroinflammation is associated with many neurodegenerative and neurocognitive disorders, yet few animal models exist to study the behavioral effects of prolonged neuroinflammation. Therefore, we recently developed a transgenic mouse model harboring an interleukin-1 beta excisional activation transgene (IL-1 beta(XAT)). These mice display localized IL-1 beta overexpression and resultant neuroinflammation for up to 1 year following transgene induction. Initial behavioral studies demonstrated long-term memory deficits after 2 weeks of hippocampal IL-1 beta overexpression. In the present studies, we extend these behavioral studies both in scope and timing. We find long-term contextual but not auditory fear memory impairments following 3 months of IL-1 beta overexpression. On a battery of other behavioral tests, IL-1 beta overexpression in IL-1 beta(XAT) mice increased locomotor activity, especially in female mice, and had slight anxiolytic effects. No differences were found in operant conditioning or in basal or stress-induced CORT levels, despite profound hippocampal glial activation. Interestingly, the volume of discrete hippocampal cell layers was reduced after 6 but not 3 months of IL-1 beta overexpression. Therefore, this animal model provides a novel tool for examining the effects of chronic inflammation on discrete brain regions.
C1 [O'Banion, M. Kerry] Univ Rochester, Med Ctr, Rochester, NY 14642 USA.
   [Hein, Amy M.; Carbonari, Dena M.; Olschowka, John A.; O'Banion, M. Kerry] Univ Rochester, Sch Med & Dent, Dept Neurobiol & Anat, Rochester, NY 14642 USA.
   [Zarcone, Troy J.] NIAAA, Bethesda, MD 20892 USA.
   [Parfitt, David B.] SUNY Coll Geneseo, Geneseo, NY 14454 USA.
   [Matousek, Sarah B.] Brigham & Womens Hosp, Boston, MA 02115 USA.
RP O'Banion, MK (reprint author), Univ Rochester, Med Ctr, 601 Elmwood Ave,Box 603, Rochester, NY 14642 USA.
EM Kerry_OBanion@urmc.rochester.edu
RI Carbonari, Dena/H-3366-2011
OI Carbonari, Dena/0000-0003-0310-270X
FU NIH [RO1 AG030149, P30 ES001247, T32 NS051152]; NINDS [NIH T32 NS051152]
FX We would like to thank S. Kyrkanides and J. Miller for FIV packaging, M.
   Olschowka and J. Walter for animal colony management, and L. Trojancyzk
   for help with tissue processing. The present work was supported by NIH
   RO1 AG030149 andP30 ES001247. A. Hein was supported by an NINDS T32
   training grant in neuroinflammation and glial cell biology (NIH T32
   NS051152).; NIH RO1 AG030149, P30 ES001247, and T32 NS051152.
NR 41
TC 12
Z9 13
U1 0
U2 2
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 MAR
PY 2012
VL 7
IS 1
SI SI
BP 145
EP 155
DI 10.1007/s11481-011-9294-3
PG 11
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 943YM
UT WOS:000304164000011
PM 21748283
ER

PT J
AU Hu, XM
   Zhou, H
   Zhang, D
   Yang, SF
   Qian, L
   Wu, HM
   Chen, PS
   Wilson, B
   Gao, HM
   Lu, RB
   Hong, JS
AF Hu, Xiaoming
   Zhou, Hui
   Zhang, Dan
   Yang, Sufen
   Qian, Li
   Wu, Hung-Ming
   Chen, Po-See
   Wilson, Belinda
   Gao, Hui-Ming
   Lu, Ru-band
   Hong, Jau-Shyong
TI Clozapine Protects Dopaminergic Neurons from Inflammation-Induced Damage
   by Inhibiting Microglial Overactivation
SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY
LA English
DT Article
DE Clozapine; Microglia; NADPH oxidase; Neurodegeneration;
   Neuroinflammation
ID ATYPICAL ANTIPSYCHOTIC-DRUGS; NADPH OXIDASE ACTIVITY; NEURODEGENERATIVE
   DISEASES; PARKINSONS-DISEASE; PC12 CELLS; CHRONIC-SCHIZOPHRENICS;
   CLASS-III; IN-VITRO; ACTIVATION; NEUROTOXICITY
AB Increasing evidence suggests a possible involvement of neuroinflammation in some psychiatric disorders, and also pharmacological reports indicate that anti-inflammatory effects are associated with therapeutic actions of psychoactive drugs, such as anti-depressants and antipsychotics. The purpose of this study was to explore whether clozapine, a widely used antipsychotic drugs, displays anti-inflammatory and neuroprotective effects. Using primary cortical and mesencephalic neuron-glia cultures, we found that clozapine was protective against inflammation-related neurodegeneration induced by lipopolysaccharide (LPS). Pretreatment of cortical or mesencephalic neuron-glia cultures with clozapine (0.1 or 1 mu M) for 24 h attenuated LPS-induced neurotoxicity. Clozapine also protected neurons against 1-methyl-4-phenylpyridinium(+) (MPP+)-induced neurotoxicity, but only in cultures containing microglia, indicating an indispensable role of microglia in clozapine-afforded neuroprotection. Further observation revealed attenuated LPS-induced microglial activation in primary neuron-glia cultures and in HAPI microglial cell line with clozapine pretreatment. Clozapine ameliorated the production of microglia-derived superoxide and intracellular reactive oxygen species (ROS), as well as the production of nitric oxide and TNF-alpha following LPS. In addition, the protective effect of clozapine was not observed in neuronglia cultures from mice lacking functional NADPH oxidase (PHOX), a key enzyme for superoxide production in immune cells. Further mechanistic studies demonstrated that clozapine pretreatment inhibited LPS-induced translocation of cytosolic subunit p47(phox) to the membrane in microglia, which was most likely through inhibiting the phosphoinositide 3-kinase (PI3K) pathway. Taken together, this study demonstrates that clozapine exerts neuroprotective effect via the attenuation of microglia activation through inhibition of PHOX-generated ROS production and suggests potential use of antipsychotic drugs for neuroprotection.
C1 [Hu, Xiaoming; Zhou, Hui; Zhang, Dan; Yang, Sufen; Qian, Li; Wu, Hung-Ming; Chen, Po-See; Wilson, Belinda; Gao, Hui-Ming; Hong, Jau-Shyong] NIEHS, Neuropharmacol Sect, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
   [Wu, Hung-Ming; Lu, Ru-band] Natl Cheng Kung Univ, Inst Behav Med, Coll Med & Hosp, Tainan 70101, Taiwan.
   [Wu, Hung-Ming; Lu, Ru-band] Natl Cheng Kung Univ, Dept Psychiat, Coll Med & Hosp, Tainan 70101, Taiwan.
   [Hu, Xiaoming] Univ Pittsburgh, Dept Neurol, Sch Med, Pittsburgh, PA 15261 USA.
   [Hu, Xiaoming] Univ Pittsburgh, Pittsburgh Inst Neurodegenerat Dis, Sch Med, Pittsburgh, PA 15261 USA.
RP Hong, JS (reprint author), NIEHS, Neuropharmacol Sect, Lab Toxicol & Pharmacol, NIH, MD F1-01,POB 12233, Res Triangle Pk, NC 27709 USA.
EM hong3@niehs.nih.gov
FU National Institute of Environmental Health Sciences, National Institute
   of Health
FX This research was supported by the Intramural Research Program of the
   National Institute of Environmental Health Sciences, National Institute
   of Health.
NR 58
TC 20
Z9 21
U1 0
U2 8
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 MAR
PY 2012
VL 7
IS 1
SI SI
BP 187
EP 201
DI 10.1007/s11481-011-9309-0
PG 15
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 943YM
UT WOS:000304164000015
PM 21870076
ER

PT J
AU Leoni, RF
   Paiva, FF
   Kang, BT
   Henning, EC
   Nascimento, GC
   Tannus, A
   de Araujo, DB
   Silva, AC
AF Leoni, Renata F.
   Paiva, Fernando F.
   Kang, Byeong-Teck
   Henning, Erica C.
   Nascimento, George C.
   Tannus, Alberto
   de Araujo, Draulio B.
   Silva, Afonso C.
TI Arterial Spin Labeling Measurements of Cerebral Perfusion Territories in
   Experimental Ischemic Stroke
SO TRANSLATIONAL STROKE RESEARCH
LA English
DT Article
DE Cerebral blood flow; Collateral flow; Magnetic resonance imaging;
   Vascular territory
ID BRAIN-FEEDING ARTERIES; COLLATERAL CIRCULATION; BLOOD-FLOW; RAT;
   OCCLUSION; MRI; HYPERTENSION; WATER; ANGIOGRAPHY; INVERSION
AB Collateral circulation, defined as the supplementary vascular network that maintains cerebral blood flow (CBF) when the main vessels fail, constitutes one important defense mechanism of the brain against ischemic stroke. In the present study, continuous arterial spin labeling (CASL) was used to quantify CBF and obtain perfusion territory maps of the major cerebral arteries in spontaneously hypertensive rats (SHRs) and their normotensive Wistar-Kyoto (WKY) controls. Results show that both WKY and SHR have complementary, yet significantly asymmetric perfusion territories. Right or left dominances were observed in territories of the anterior (ACA), middle and posterior cerebral arteries, and the thalamic artery. Magnetic resonance angiography showed that some of the asymmetries were correlated with variations of the ACA. The leptomeningeal circulation perfusing the outer layers of the cortex was observed as well. Significant and permanent changes in perfusion territories were obtained after temporary occlusion of the right middle cerebral artery in both SHR and WKY, regardless of their particular dominance. However, animals with right dominance presented a larger volume change of the left perfusion territory (23 +/- 9%) than animals with left dominance (7 +/- 5%, P<0.002). The data suggest that animals with contralesional dominance primarily safeguard local CBF values with small changes in contralesional perfusion territory, while animals with ipsilesional dominance show a reversal of dominance and a substantial increase in contralesional perfusion territory. These findings show the usefulness of CASL to probe the collateral circulation.
C1 [Leoni, Renata F.; Paiva, Fernando F.; Kang, Byeong-Teck; 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.] Univ Sao Paulo, FFCLRP, Dept Fis, BR-14040901 Sao Paulo, Brazil.
   [Paiva, Fernando F.; Tannus, Alberto] Univ Sao Paulo, IFSC, Dept Fis & Informat, BR-13560970 Sao Paulo, Brazil.
   [Henning, Erica C.] Natl Inst Neurol Disorders & Stroke, Sect Stroke Diagnost & Therapeut, NIH, Bethesda, MD 20892 USA.
   [de Araujo, Draulio B.] Univ Fed Rio Grande Norte UFRN, Hosp Univ Onorio Lopes, Inst Cerebro, BR-59056045 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 B1D106, Bethesda, MD 20892 USA.
EM SilvaA@ninds.nih.gov
RI Araujo, Draulio/I-6038-2012; Sao Carlos Institute of Physics,
   IFSC/USP/M-2664-2016; Tannus, Alberto/B-9821-2012; 
OI Araujo, Draulio/0000-0002-6934-2485; Tannus,
   Alberto/0000-0002-1675-1971; Leoni, Renata/0000-0002-4568-0746; Paiva,
   Fernando/0000-0002-8989-9707
FU NIH, NINDS; FAPESP [2006/05706-5, 2003/13399-7, 2005/56663-1]
FX The authors acknowledge the excellent technical assistance of Mrs.
   Xianfeng (Lisa) Zhang. 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 38
TC 4
Z9 5
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1868-4483
J9 TRANSL STROKE RES
JI Transl. Stroke Res.
PD MAR
PY 2012
VL 3
IS 1
SI SI
BP 44
EP 55
DI 10.1007/s12975-011-0115-z
PG 12
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 943YP
UT WOS:000304164300007
PM 24323754
ER

PT J
AU Kummar, S
AF Kummar, S.
TI DEVELOPMENT OF MARKERS OF DNA REPAIR
SO ANNALS OF ONCOLOGY
LA English
DT Meeting Abstract
CT 10th International Symposium on Targeted Anticancer Therapies
CY MAR 08-10, 2012
CL Amsterdam, NETHERLANDS
C1 [Kummar, S.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
J9 ANN ONCOL
JI Ann. Oncol.
PD MAR
PY 2012
VL 23
SU 1
BP 18
EP 18
PG 1
WC Oncology
SC Oncology
GA 940CH
UT WOS:000303867100019
ER

PT J
AU Pommier, Y
   Das, BB
   Regairaz, M
   Zhang, Y
AF Pommier, Y.
   Das, B. B.
   Regairaz, M.
   Zhang, Y.
TI PARP INHIBITION AND EFFICACY OF TOPOISOMERASE I INHIBITORS
SO ANNALS OF ONCOLOGY
LA English
DT Meeting Abstract
CT 10th International Symposium on Targeted Anticancer Therapies
CY MAR 08-10, 2012
CL Amsterdam, NETHERLANDS
C1 [Pommier, Y.; Das, B. B.; Regairaz, M.; Zhang, Y.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
J9 ANN ONCOL
JI Ann. Oncol.
PD MAR
PY 2012
VL 23
SU 1
BP 19
EP 19
PG 1
WC Oncology
SC Oncology
GA 940CH
UT WOS:000303867100022
ER

PT J
AU Seymour, L
   Ivy, SP
   Hilton, J
   Dancey, J
   Paller, C
AF Seymour, L.
   Ivy, S. P.
   Hilton, J.
   Dancey, J.
   Paller, C.
TI CLINICAL INTERACTIONS WITH COMBINATION OF NOVEL AGENTS
SO ANNALS OF ONCOLOGY
LA English
DT Meeting Abstract
CT 10th International Symposium on Targeted Anticancer Therapies
CY MAR 08-10, 2012
CL Amsterdam, NETHERLANDS
C1 [Seymour, L.; Hilton, J.; Dancey, J.] NCIC Clin Trials Grp, Kingston, ON, Canada.
   [Ivy, S. P.; Paller, C.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
J9 ANN ONCOL
JI Ann. Oncol.
PD MAR
PY 2012
VL 23
SU 1
BP 19
EP 19
PG 1
WC Oncology
SC Oncology
GA 940CH
UT WOS:000303867100024
ER

PT J
AU Bates, SE
AF Bates, S. E.
TI EPIGENETIC TARGETS: ESTABLISHED AND IN THE PIPELINE
SO ANNALS OF ONCOLOGY
LA English
DT Meeting Abstract
CT 10th International Symposium on Targeted Anticancer Therapies
CY MAR 08-10, 2012
CL Amsterdam, NETHERLANDS
C1 [Bates, S. E.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
J9 ANN ONCOL
JI Ann. Oncol.
PD MAR
PY 2012
VL 23
SU 1
BP 23
EP 23
PG 1
WC Oncology
SC Oncology
GA 940CH
UT WOS:000303867100039
ER

PT J
AU Avan, A
   Paolicchi, E
   Crea, F
   Funel, N
   Galvani, E
   Marquez, V
   Honeywell, R
   Danesi, R
   Peters, GJ
   Giovannetti, E
AF Avan, A.
   Paolicchi, E.
   Crea, F.
   Funel, N.
   Galvani, E.
   Marquez, V.
   Honeywell, R.
   Danesi, R.
   Peters, G. J.
   Giovannetti, E.
TI EZH2 AS A NOVEL THERAPEUTIC TARGET FOR TREATMENT OF PANCREATIC DUCTAL
   ADENOCARCINOMA
SO ANNALS OF ONCOLOGY
LA English
DT Meeting Abstract
CT 10th International Symposium on Targeted Anticancer Therapies
CY MAR 08-10, 2012
CL Amsterdam, NETHERLANDS
C1 [Avan, A.; Galvani, E.; Honeywell, R.; Peters, G. J.; Giovannetti, E.] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands.
   [Paolicchi, E.; Crea, F.; Funel, N.; Danesi, R.] Univ Pisa, Pisa, Italy.
   [Marquez, V.] NIH, Frederick, MD USA.
RI Galvani, Elena/L-3133-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
J9 ANN ONCOL
JI Ann. Oncol.
PD MAR
PY 2012
VL 23
SU 1
BP 31
EP 32
PG 2
WC Oncology
SC Oncology
GA 940CH
UT WOS:000303867100075
ER

PT J
AU Voortman, J
   Harada, T
   Chang, RP
   Killian, JK
   Suuriniemi, M
   Smith, WIJR
   Meltzer, PS
   Lucchi, M
   Giaccone, G
AF Voortman, J.
   Harada, T.
   Chang, R. P.
   Killian, J. K.
   Suuriniemi, M.
   Smith, W. I. J. R.
   Meltzer, P. S.
   Lucchi, M.
   Giaccone, G.
TI MUTATION ANALYSIS OF C-MET IN SMALL CELL LUNG CANCER AND NEUROENDOCRINE
   TUMORS
SO ANNALS OF ONCOLOGY
LA English
DT Meeting Abstract
CT 10th International Symposium on Targeted Anticancer Therapies
CY MAR 08-10, 2012
CL Amsterdam, NETHERLANDS
C1 [Voortman, J.] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands.
   [Harada, T.; Chang, R. P.; Killian, J. K.; Suuriniemi, M.; Meltzer, P. S.; Giaccone, G.] NCI, Bethesda, MD 20892 USA.
   [Smith, W. I. J. R.] Suburban Hosp, Bethesda, MD USA.
   [Lucchi, M.] Univ Pisa, Pisa, Italy.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
J9 ANN ONCOL
JI Ann. Oncol.
PD MAR
PY 2012
VL 23
SU 1
BP 34
EP 34
PG 1
WC Oncology
SC Oncology
GA 940CH
UT WOS:000303867100083
ER

PT J
AU Kagiya, GK
   Ogawa, R
   Hatashita, M
   Tanaka, Y
   Kouda, K
   Fukuda, S
   Mitchell, JB
AF Kagiya, G. K.
   Ogawa, R.
   Hatashita, M.
   Tanaka, Y.
   Kouda, K.
   Fukuda, S.
   Mitchell, J. B.
TI ENHANCEMENT OF HYPOXIC CELL KILLING BY THE NITROXIDE TEMPOL
SO ANNALS OF ONCOLOGY
LA English
DT Meeting Abstract
CT 10th International Symposium on Targeted Anticancer Therapies
CY MAR 08-10, 2012
CL Amsterdam, NETHERLANDS
C1 [Kagiya, G. K.] Kitasato Univ, Sagamihara, Kanagawa 228, Japan.
   [Ogawa, R.] Toyama Univ, Toyama 930, Japan.
   [Hatashita, M.; Tanaka, Y.] Wakasa Wan Energy Res Ctr, Tsuruga, Fukui, Japan.
   [Kouda, K.; Fukuda, S.] Natl Inst Radiol Sci, Chiba 260, Japan.
   [Mitchell, J. B.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
J9 ANN ONCOL
JI Ann. Oncol.
PD MAR
PY 2012
VL 23
SU 1
BP 36
EP 37
PG 2
WC Oncology
SC Oncology
GA 940CH
UT WOS:000303867100092
ER

PT J
AU Menefee, M
   Bible, K
   Reidy-Lagunes, D
   Kane, M
   Allred, J
   Takebe, N
   Ehrlichman, C
   Shah, M
AF Menefee, M.
   Bible, K.
   Reidy-Lagunes, D.
   Kane, M.
   Allred, J.
   Takebe, N.
   Ehrlichman, C.
   Shah, M.
TI A PHASE II STUDY AT-101 IN PATIENTS WITH ADVANCED ADRENAL CORTICAL
   CARCINOMA (ACC)
SO ANNALS OF ONCOLOGY
LA English
DT Meeting Abstract
CT 10th International Symposium on Targeted Anticancer Therapies
CY MAR 08-10, 2012
CL Amsterdam, NETHERLANDS
C1 [Menefee, M.] Mayo Clin, Jacksonville, FL 32224 USA.
   [Bible, K.; Allred, J.; Ehrlichman, C.] Mayo Clin, Rochester, MN USA.
   [Reidy-Lagunes, D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
   [Kane, M.] Univ Colorado, Denver, CO 80202 USA.
   [Takebe, N.] NCI, Rockville, MD USA.
   [Shah, M.] Ohio State Univ, Columbus, OH 43210 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
J9 ANN ONCOL
JI Ann. Oncol.
PD MAR
PY 2012
VL 23
SU 1
BP 42
EP 42
PG 1
WC Oncology
SC Oncology
GA 940CH
UT WOS:000303867100113
ER

PT J
AU Ogbureke, KUE
   Weinberger, PM
   Looney, SW
   Li, L
   Fisher, LW
AF Ogbureke, Kalu U. E.
   Weinberger, Paul M.
   Looney, Stephen W.
   Li, Li
   Fisher, Larry W.
TI Expressions of matrix metalloproteinase-9 (MMP-9), dentin
   sialophosphoprotein (DSPP), and osteopontin (OPN) at histologically
   negative surgical margins may predict recurrence of oral squamous cell
   carcinoma
SO ONCOTARGET
LA English
DT Article
DE Oral Cancer; DSPP; BSP; OPN; MMPs; Tumor-Free Margin
ID LINKED GLYCOPROTEINS SIBLINGS; NECK-CANCER; MATRIX METALLOPROTEINASES;
   HEAD; PROTEINS; EIF4E; TRANSITION; MEMBERS; TONGUE; FAMILY
AB Up to 50% of oral squamous cell carcinomas (OSCCs) recur following surgical resections with conventional "histologically-negative" margins. Three members of the SIBLING (Small Integrin Binding LIgand N-linked Gylcoprotein) family of proteins: dentin sialophophoprotein (DSPP); bone sialoprotein (BSP); and osteopontin OPN are upregulated in OSCCs. In this study, we aimed to correlate the expression of DSPP, OPN and BSP as well as three SIBLING-partners, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-3 (MMP-3), and matrix metalloproteinase-9 (MMP-9), at histologically-negative margins of OSCCs with tumor recurrence. Immunohistochemical analyses of the SIBLINGs and MMP expressions at histologically-negative margins of OSCC was carried out in a retrospective study of 20 patients, and the results correlated with tumor recurrence. Each protein was dichotomized as "present" (>= 10% staining) or " absent" (< 10% staining). The Sensitivity, Specificity, Positive Predictive Value(PV+) and Negative Predictive Value (PV-) for recurrence was calculated for each protein, along with their overall diagnostic accuracy, calculated as: (number of true positives + number of true negatives)/number of patients. OSCC recurred in 9 of 20 patients (45%), a ratio not significantly different from the estimated population recurrence rate of 50% (p = 0.664). Among the SIBLINGs, DSPP and OPN showed the greatest Accuracy with DSPP being more Sensitive (89%) and OPN more Specific (64%). MMP-9 showed the greatest overall Accuracy (80%), slightly less Sensitivity (67%) and more Specificity (100%), than either DSPP or OPN. MMP-9 showed a superior positive PV than either DSPP or OPN. The negative PVs of OPN and MMP-9 were almost identical, and inferior to DSPP. We conclude that DSPP, OPN, or MMP-9 expressions at histologically-negative surgical margins predict OSCC recurrence, with MMP-9 being the preferred predictor. These proteins may identify patients who could benefit from more extensive resection, or from adjunct treatments such as radiotherapy.
C1 [Ogbureke, Kalu U. E.; Looney, Stephen W.] Georgia Hlth Sci Univ, Coll Dent Med, Augusta, GA USA.
   [Ogbureke, Kalu U. E.; Weinberger, Paul M.] Georgia Hlth Sci Univ, Med Coll Georgia, Augusta, GA USA.
   [Ogbureke, Kalu U. E.; Looney, Stephen W.] Georgia Hlth Sci Univ, Coll Grad Studies, Augusta, GA USA.
   [Li, Li; Fisher, Larry W.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA.
RP Ogbureke, KUE (reprint author), Georgia Hlth Sci Univ, Coll Dent Med, 1120 15th St, Augusta, GA USA.
EM kogbureke@georgiahealth.edu
RI Weinberger, Paul/B-7007-2008
OI Weinberger, Paul/0000-0002-5885-2631
FU National Institute of Dental and Craniofacial Research (NIDCR), National
   Institutes of Health (NIH) [K23DE017791-01A1]; Division of Intramural
   Research, National Institute of Dental and Craniofacial Research of the
   National Institutes of Health
FX Study was supported by Grant # K23DE017791-01A1 (KUEO) from the National
   Institute of Dental and Craniofacial Research (NIDCR), National
   Institutes of Health (NIH), and by the Division of Intramural Research,
   National Institute of Dental and Craniofacial Research, of the
   Intramural Research Program of the National Institutes of Health (LL &
   LWF).
NR 24
TC 18
Z9 18
U1 0
U2 2
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD MAR
PY 2012
VL 3
IS 3
BP 286
EP 298
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 941WD
UT WOS:000303997100007
PM 22410369
ER

PT J
AU Yuan, HY
   Kopelovich, L
   Yin, YZ
   Lu, J
   Glazer, RI
AF Yuan, Hongyan
   Kopelovich, Levy
   Yin, Yuzhi
   Lu, Jin
   Glazer, Robert I.
TI Drug-Targeted Inhibition of Peroxisome Proliferator-Activated Receptor.
   Enhances the Chemopreventive Effect of Anti-Estrogen
SO ONCOTARGET
LA English
DT Article
DE PPAR gamma; ER alpha; fulvestrant; GW9662
ID PPAR-GAMMA; ESTROGEN-RECEPTOR; ADIPOCYTE DIFFERENTIATION; MAMMARY
   CARCINOGENESIS; LIGAND-BINDING; ANTAGONIST; CARCINOMA; AGONIST; CELLS;
   DELTA
AB The peroxisome proliferator-activated receptor gamma (PPAR gamma) is a key regulator of metabolism, proliferation, inflammation and differentiation, and upregulates tumor suppressor genes, such as PTEN, BRCA1 and PPAR gamma itself. Examination of mammary carcinogenesis in transgenic mice expressing the dominant-negative Pax8PPAR gamma fusion protein revealed that tumors were estrogen receptora (ER)-positive and sensitive to the ER antagonist, fulvestrant. Here we evaluated whether administration of an irreversible PPAR gamma inhibitor in vivo could similarly induce ER expression in otherwise ER-negative mammary tumors following induction of carcinogenesis, and sensitize them to the antitumor effects of fulvestrant. In addition, we wished to determine whether the effect of GW9662 was associated with a PPAR-selective gene expression profile. Mammary carcinogenesis was induced in wild-type FVB mice by treatment with medroxyprogesterone and dimethylbenz(a) anthracene (DMBA) that were subsequently maintained on a diet supplemented with 0.1% GW9662, and tumorigenesis and gene expression profiling of the resulting tumors were determined. Administration of GW9962 resulted in ER+ tumors that were highly sensitive to fulvestrant. Tumors from GW9662-treated animals exhibited reduced expression of a metabolic gene profile indicative of PPAR gamma inhibition, including PPAR gamma itself. Additionally, GW9662 upregulated the expression of several genes associated with the transcription, processing, splicing and translation of RNA. This study is the first to show that an irreversible PPAR gamma inhibitor can mimic a dominant-negative PPAR gamma transgene to elicit the development of ER-responsive tumors. These findings suggest that it may be possible to pharmacologically influence the responsiveness of tumors to anti-estrogen therapy.
C1 [Yuan, Hongyan; Yin, Yuzhi; Lu, Jin; Glazer, Robert I.] Georgetown Univ, Sch Med, Dept Oncol, Washington, DC USA.
   [Yuan, Hongyan; Yin, Yuzhi; Lu, Jin; Glazer, Robert I.] Lombardi Comprehens Canc Ctr, Washington, DC USA.
   [Kopelovich, Levy] NCI, Chemoprevent Branch, Bethesda, MD 20892 USA.
   [Yin, Yuzhi] NIAID, Lab Allerg Dis, Bethesda, MD 20892 USA.
RP Glazer, RI (reprint author), Georgetown Univ, Sch Med, Dept Oncol, Washington, DC USA.
EM glazerr@georgetown.edu
FU National Cancer Institute, NIH [1NO1 CN43302-WA19, P30CA051008]; NIH
FX This study was supported by contract 1NO1 CN43302-WA19 from the National
   Cancer Institute, NIH, and award P30CA051008 from the National Cancer
   Institute, NIH to the Lombardi Comprehensive Cancer Center (LCCC). This
   investigation was conducted using the Animal Research, Flow Cytometry,
   Genomics and Epigenomics, and Microscopy and Imaging Shared Resources of
   the LCCC, and by an animal facilities construction grant from the NIH.
NR 36
TC 10
Z9 12
U1 0
U2 2
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD MAR
PY 2012
VL 3
IS 3
BP 345
EP 356
PG 12
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 941WD
UT WOS:000303997100012
PM 22538444
ER

PT J
AU Miller, FG
AF Miller, Franklin G.
TI HOMAGE TO HENRY BEECHER (1904-1976)
SO PERSPECTIVES IN BIOLOGY AND MEDICINE
LA English
DT Article
ID BRAIN-DEATH; CLINICAL-RESEARCH; RANDOMIZED-TRIAL; POWERFUL PLACEBO;
   SURGERY; VERTEBROPLASTY; DEFINITIONS; FRACTURES; CRITERIA; SCIENCE
AB The writings of Henry Beecher (1904-1976) have had an enormous influence on thinking and practice with respect to the ethics of medicine and clinical research. This essay examines the seminal contributions of Beecher as illustrated by four landmark articles concerning the ethics of clinical research, the placebo effect and placebo-controlled trials, the evaluation of invasive procedures, and "brain death" and vital organ transplantation. To appreciate Beecher's legacy, it is salutary to explicate the significance of his enduring contributions and to critically evaluate their limitations.
C1 NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
RP Miller, FG (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
EM fmiller@nih.gov
FU Clinical Center, NIH
FX The opinions expressed are the views of the author and do not
   necessarily reflect the policy of the National Institutes of Health, the
   Public Health Service, or the U.S. Department of Health and Human
   Services.This research was supported by the Intramural Research Program
   of the Clinical Center, NIH.
NR 51
TC 2
Z9 2
U1 0
U2 3
PU JOHNS HOPKINS UNIV PRESS
PI BALTIMORE
PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD
   21218-4363 USA
SN 0031-5982
J9 PERSPECT BIOL MED
JI Perspect. Biol. Med.
PD SPR
PY 2012
VL 55
IS 2
BP 218
EP 229
PG 12
WC History & Philosophy Of Science; Medicine, Research & Experimental
SC History & Philosophy of Science; Research & Experimental Medicine
GA 939UF
UT WOS:000303843500006
PM 22643759
ER

PT J
AU Persson, EC
   Sewram, V
   Evans, AA
   London, WT
   Volkwyn, Y
   Shen, YJ
   Van Zyl, JA
   Chen, G
   Lin, WY
   Shephard, GS
   Taylor, PR
   Fan, JH
   Dawsey, SM
   Qiao, YL
   McGlynn, KA
   Abnet, CC
AF Persson, E. Christina
   Sewram, Vikash
   Evans, Alison A.
   London, W. Thomas
   Volkwyn, Yvette
   Shen, Yen-Ju
   Van Zyl, Jacobus A.
   Chen, Gang
   Lin, Wenyao
   Shephard, Gordon S.
   Taylor, Philip R.
   Fan, Jin-Hu
   Dawsey, Sanford M.
   Qiao, You-Lin
   McGlynn, Katherine A.
   Abnet, Christian C.
TI Fumonisin B-1 and risk of hepatocellular carcinoma in two Chinese
   cohorts
SO FOOD AND CHEMICAL TOXICOLOGY
LA English
DT Article
DE Fumonisin; Hepatocellular carcinoma; Cohort study; China; Epidemiology
ID PRIMARY LIVER-CANCER; REPUBLIC-OF-CHINA; ESOPHAGEAL CANCER; HAIMEN-CITY;
   FOLLOW-UP; CORN; MYCOTOXINS; EXPOSURE; MORTALITY; HAIR
AB Fumonisin B-1 (FB1), a mycotoxin that contaminates corn in certain climates, has been demonstrated to cause hepatocellular cancer (HCC) in animal models. Whether a relationship between FB1 and HCC exists in humans is not known. To examine the hypothesis, we conducted case-control studies nested within two large cohorts in China; the Haimen City Cohort and the General Population Study of the Nutritional Intervention Trials cohort in Linxian. In the Haimen City Cohort, nail FB1 levels were determined in 271 HCC cases and 280 controls. In the General Population Nutritional Intervention Trial, nail FB1 levels were determined in 72 HCC cases and 147 controls. In each population, odds ratios and 95% confidence intervals (95%CI) from logistic regression models estimated the association between measurable FB1 and HCC, adjusting for hepatitis B virus infection and other factors. A meta-analysis that included both populations was also conducted. The analysis revealed no statistically significant association between FB1 and HCC in either Haimen City (OR = 1.10, 95%CI = 0.64-1.89) or in Linxian (OR = 1.47, 95%CI = 0.70-3.07). Similarly, the pooled meta-analysis showed no statistically significant association between FB1 exposure and HCC (OR = 1.22, 95%CI = 0.79-1.89). These findings, although somewhat preliminary, do not support an associated between FB1 and HCC. Published by Elsevier Ltd.
C1 [Persson, E. Christina; Taylor, Philip R.; Dawsey, Sanford M.; McGlynn, Katherine A.; Abnet, Christian C.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
   [Sewram, Vikash; Shen, Yen-Ju] MRC, Oncol Res Unit, Durban, South Africa.
   [Evans, Alison A.] Drexel Univ, Sch Publ Hlth, Philadelphia, PA 19104 USA.
   [London, W. Thomas] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
   [Volkwyn, Yvette; Shephard, Gordon S.] MRC, PROMEC Unit, Tygerberg, South Africa.
   [Van Zyl, Jacobus A.] MRC, Indigenous Knowledge Syst Res Unit, Cape Town, South Africa.
   [Chen, Gang] Hepatitis B Fdn, Doylestown, PA USA.
   [Lin, Wenyao] Haimen City Ctr Dis Control, Haimen City, Peoples R China.
   [Fan, Jin-Hu; Qiao, You-Lin] Chinese Acad Med Sci, Canc Inst Hosp, Beijing 100730, Peoples R China.
RP Persson, EC (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS Suite 550,Room 5008, Rockville, MD 20852 USA.
EM christina.persson@nih.gov
RI Evans, Alison/I-4970-2013; Qiao, You-Lin/B-4139-2012; Abnet,
   Christian/C-4111-2015
OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843
FU Intramural NIH HHS [Z99 CA999999]
NR 34
TC 6
Z9 6
U1 0
U2 13
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0278-6915
EI 1873-6351
J9 FOOD CHEM TOXICOL
JI Food Chem. Toxicol.
PD MAR-APR
PY 2012
VL 50
IS 3-4
BP 679
EP 683
DI 10.1016/j.fct.2011.11.029
PG 5
WC Food Science & Technology; Toxicology
SC Food Science & Technology; Toxicology
GA 932IR
UT WOS:000303284600035
PM 22142693
ER

PT J
AU Chatterjee, D
   Chandran, B
   Berger, EA
AF Chatterjee, Deboeeta
   Chandran, Bala
   Berger, Edward A.
TI Selective killing of Kaposi's sarcoma-associated herpesvirus lytically
   infected cells with a recombinant immunotoxin targeting the viral
   gpK8.1A envelope glycoprotein
SO MABS
LA English
DT Article
DE targeted cytotoxic proteins; human herpesvirus-8; KSHV surface
   glycoprotein; KSHV lytic infection; multicentric Castleman disease;
   pseudomonas exotoxin A; ganciclovir; reciprocal drug potentiation
ID MULTICENTRIC CASTLEMANS-DISEASE; HUMAN-IMMUNODEFICIENCY-VIRUS; PRIMARY
   EFFUSION LYMPHOMA; CD4-PSEUDOMONAS EXOTOXIN; CYTOTOXIC THERAPY; FUSION
   PROTEINS; DNA-SEQUENCES; HUMAN-HERPESVIRUS-8 REPLICATION;
   MONOCLONAL-ANTIBODY; HEPARAN-SULFATE
AB Kaposi sarcoma-associated herpesvirus (KSHV, human herpesvirus 8) is etiologically associated with three neoplastic syndromes: Kaposi sarcoma and the uncommon HIV-associated B-cell lymphoproliferative disorders primary effusion lymphoma and multicentric Castleman disease. The incidence of the latter B-cell pathology has been increasing in spite of antiretroviral therapy; its association with lytic virus replication has prompted interest in therapeutic strategies aimed at this phase of the virus life cycle. We designed and expressed a recombinant immunotoxin (2014-PE38) targeting the gpK8.1A viral glycoprotein expressed on the surface of the virion and infected cells. We show that this immunotoxin selectively kills KSHV-infected cells in dose-dependent fashion, resulting in major reductions of infectious virus release. The immunotoxin and ganciclovir, an inhibitor of viral DNA replication, showed marked reciprocal potentiation of antiviral activities. These results suggest that the immunotoxin, alone or in combination, may represent a new approach to treat diseases associated with KSHV lytic replication.
C1 [Chatterjee, Deboeeta; Berger, Edward A.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
   [Chandran, Bala] Rosalind Franklin Univ Med & Sci, Dept Microbiol & Immunol, Chicago, IL USA.
RP Berger, EA (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
EM edward_berger@nih.gov
FU NIH, NIAID
FX We thank Jeffrey Vieira (University of Washington, Seattle WA) for
   donating the recombinant KSHV-infected stable cell lines as well as
   Joseph Newland and George Katsafanas (NIAID, NIH) for technical support
   as well as John Weldon, Tapan Bera and Ira Pastan (NCI, NIH) for
   providing control PE-based immunotoxins and technical advice. We are
   grateful to Bertrand Saunier and Yingyun Cai (NIAID, NIH) for sharing
   experimental insights. The excellent technical assistance of Virgilio
   Bundoc (NIAID, NIH) is acknowledged. This work was funded in part by the
   Intramural Program of the NIH, NIAID.
NR 95
TC 6
Z9 6
U1 0
U2 2
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1942-0862
J9 MABS-AUSTIN
JI mAbs
PD MAR-APR
PY 2012
VL 4
IS 2
BP 233
EP 242
DI 10.4161/mabs.4.2.19262
PG 10
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 936MJ
UT WOS:000303594200007
PM 22377676
ER

PT J
AU Chung, JH
AF Chung, Jay H.
TI Using PDE inhibitors to harness the benefits of calorie restriction:
   lessons from resveratrol
SO AGING-US
LA English
DT Editorial Material
ID ACTIVATED PROTEIN-KINASE; SIRT1 ACTIVATION; SKELETAL-MUSCLE; AMPK;
   EXERCISE; SIRTUINS
C1 NHLBI, Lab Obes & Aging Res, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA.
RP Chung, JH (reprint author), NHLBI, Lab Obes & Aging Res, Genet & Dev Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM chungj@nhlbi.nih.gov
NR 18
TC 14
Z9 14
U1 0
U2 2
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1945-4589
J9 AGING-US
JI Aging-US
PD MAR
PY 2012
VL 4
IS 3
BP 144
EP 145
PG 2
WC Cell Biology
SC Cell Biology
GA 931SV
UT WOS:000303240500001
PM 22388573
ER

PT J
AU Jirapongsananuruk, O
   Luangwedchakarn, V
   Niemela, JE
   Pacharn, P
   Visitsunthorn, N
   Thepthai, C
   Vichyanond, P
   Piboonpocanun, S
   Fleisher, TA
AF Jirapongsananuruk, Orathai
   Luangwedchakarn, Voravich
   Niemela, Julie E.
   Pacharn, Punchama
   Visitsunthorn, Nualanong
   Thepthai, Charin
   Vichyanond, Pakit
   Piboonpocanun, Surapon
   Fleisher, Thomas A.
TI Cryptococcal osteomyelitis hi a child with a novel compound mutation of
   the IL12RB1 gene
SO ASIAN PACIFIC JOURNAL OF ALLERGY AND IMMUNOLOGY
LA English
DT Article
DE Cryptococcal osteomyelitis; IL-12R beta 1 deficiency; Mycobacterial
   infection; recurrent Salmonella infection
ID DEFICIENCY; MYCOBACTERIAL; FEATURES; IMMUNITY; PATIENT
AB The IL-12p40/IL-12R beta 1 and IFN-gamma R1/IFN-gamma R2/STAT1 signaling pathways are important for clearing intracellular bacteria. Genetic defects within these pathways are associated with increased susceptibility to intracellular pathogens. Among these, IL-12R beta 1 deficiency is the most common defect and leads to infections with Salmonella and Mycobacterium spp.
   We report a child who presented with Cryptococcal osteomyelitis and history of disseminated Mycobacterial infection and recurrent Salmonella septicemia. Flow cytometry showed defective expression of IL-12R beta 1. Mutation analysis revealed a novel compound heterozygous mutation of IL12RB1, c.625C>T, p.Q209X was found in exon 7 on the paternal allele and c.710delC, p.P237HfsX5 was found in exon 8 on the maternal allele. As these mutations each result in a stop codon before the last spliceable exon, the transcripts likely underwent nonsense mediated decay, leading to a lack of IL12R beta 1 expression on the cell surface and eradicating signaling via the IL12 signaling pathway. (Asian Pac J Allergy Immunol 2012;30:79-82)
C1 [Jirapongsananuruk, Orathai; Pacharn, Punchama; Visitsunthorn, Nualanong; Vichyanond, Pakit] Mahidol Univ, Siriraj Hosp, Fac Med, Dept Pediat, Bangkok 10700, Thailand.
   [Luangwedchakarn, Voravich; Thepthai, Charin] Mahidol Univ, Siriraj Hosp, Fac Med, Dept Immunol, Bangkok 10700, Thailand.
   [Niemela, Julie E.; Fleisher, Thomas A.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
   [Piboonpocanun, Surapon] Mahidol Univ, Inst Mol Biol & Genet, Nakhon Pathom, Thailand.
RP Jirapongsananuruk, O (reprint author), Mahidol Univ, Siriraj Hosp, Fac Med, Dept Pediat, Bangkok 10700, Thailand.
EM siojr@mahidol.ac.th
NR 17
TC 6
Z9 6
U1 1
U2 3
PU ALLERGY IMMUNOL SOC THAILAND,
PI BANGKOK
PA MAHIDOL UNIV, DEPT MICROBIOL IMMUNOL, FACULTY TROPICAL MED, BANGKOK
   10400, THAILAND
SN 0125-877X
J9 ASIAN PAC J ALLERGY
JI Asian Pac. J. Allergy Immunol.
PD MAR
PY 2012
VL 30
IS 1
BP 79
EP 82
PG 4
WC Allergy; Immunology
SC Allergy; Immunology
GA 928LU
UT WOS:000302985100012
PM 22523911
ER

PT J
AU Malinovsky, Y
   Albert, PS
   Schisterman, EF
AF Malinovsky, Yaakov
   Albert, Paul S.
   Schisterman, Enrique F.
TI Pooling Designs for Outcomes under a Gaussian Random Effects Model
SO BIOMETRICS
LA English
DT Article
DE Covariance structure; Intraclass correlation coefficient; Pooling;
   Random effects model
ID ROC CURVE ANALYSIS; POOLED ASSESSMENTS; REGRESSION-MODELS; DEFECTIVE
   MEMBERS; LARGE POPULATIONS; MESSENGER-RNA; BIOMARKERS; EFFICIENCY; WOMEN
AB Due to the rising cost of laboratory assays, it has become increasingly common in epidemiological studies to pool biospecimens. This is particularly true in longitudinal studies, where the cost of performing multiple assays over time can be prohibitive. In this article, we consider the problem of estimating the parameters of a Gaussian random effects model when the repeated outcome is subject to pooling. We consider different pooling designs for the efficient maximum likelihood estimation of variance components, with particular attention to estimating the intraclass correlation coefficient. We evaluate the efficiencies of different pooling design strategies using analytic and simulation study results. We examine the robustness of the designs to skewed distributions and consider unbalanced designs. The design methodology is illustrated with a longitudinal study of premenopausal women focusing on assessing the reproducibility of F2-isoprostane, a biomarker of oxidative stress, over the menstrual cycle.
C1 [Malinovsky, Yaakov; Albert, Paul S.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA.
RP Malinovsky, Y (reprint author), Univ Maryland Baltimore Cty, Dept Math & Stat, Baltimore, MD 21250 USA.
EM yaakovm@umbc.edu
OI Schisterman, Enrique/0000-0003-3757-641X
FU American Chemistry Council; Eunice Kennedy Shriver National Institute of
   Child Health & Human Development
FX The work was supported with funding from the American Chemistry Council
   and the Intramural Research Program of the Eunice Kennedy Shriver
   National Institute of Child Health & Human Development. We thank Drs
   Zhiwei Zhang, Aijun Ye, and Sunni Mumford for helpful discussions. We
   also thank Sara Joslyn for editing the article. An associate editor and
   two referees made comments that resulted in significant improvements in
   the article.
NR 23
TC 12
Z9 12
U1 1
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0006-341X
J9 BIOMETRICS
JI Biometrics
PD MAR
PY 2012
VL 68
IS 1
BP 45
EP 52
DI 10.1111/j.1541-0420.2011.01673.x
PG 8
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
   Biology; Mathematics
GA 914BT
UT WOS:000301924400006
PM 21981372
ER

PT J
AU Korn, EL
AF Korn, Edward L.
TI Discussion of the Paper of Ghosh, Taylor, and Sargent
SO BIOMETRICS
LA English
DT Article
ID END-POINTS; ASSESSING SURROGATES; MIXED MODELS; TRIAL
C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA.
RP Korn, EL (reprint author), NCI, Biometr Res Branch, Bethesda, MD 20892 USA.
EM korne@ctep.nci.nih.gov
NR 9
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0006-341X
J9 BIOMETRICS
JI Biometrics
PD MAR
PY 2012
VL 68
IS 1
BP 236
EP 238
DI 10.1111/j.1541-0420.2011.01635.x
PG 3
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
   Biology; Mathematics
GA 914BT
UT WOS:000301924400031
PM 21668901
ER

PT J
AU Berger, VW
   Izmirlian, G
   Knoll, D
AF Berger, Vance W.
   Izmirlian, Grant
   Knoll, Diana
TI Discussion of the Paper of Ghosh, Taylor, and Sargent
SO BIOMETRICS
LA English
DT Article
ID SURROGATE END-POINTS; CLINICAL-TRIALS
C1 [Berger, Vance W.; Izmirlian, Grant; Knoll, Diana] NCI, Biometry Res Grp, Bethesda, MD 20892 USA.
RP Berger, VW (reprint author), NCI, Biometry Res Grp, Execut Plaza N,Suite 3131,6130 Execut Blvd,MSC 73, Bethesda, MD 20892 USA.
EM izmirlig@mail.nih.gov
NR 9
TC 1
Z9 1
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0006-341X
J9 BIOMETRICS
JI Biometrics
PD MAR
PY 2012
VL 68
IS 1
BP 239
EP 241
DI 10.1111/j.1541-0420.2011.01636.x
PG 3
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
   Biology; Mathematics
GA 914BT
UT WOS:000301924400032
PM 21696380
ER

PT J
AU Baker, SG
   Sargent, DJ
   Buyse, M
   Burzykowski, T
AF Baker, Stuart G.
   Sargent, Daniel J.
   Buyse, Marc
   Burzykowski, Tomasz
TI Predicting Treatment Effect from Surrogate Endpoints and Historical
   Trials: An Extrapolation Involving Probabilities of a Binary Outcome or
   Survival to a Specific Time
SO BIOMETRICS
LA English
DT Article
DE Principal stratification; Randomized trials; Reproducibility
ID ADVANCED COLORECTAL-CANCER; RANDOMIZED CLINICAL-TRIALS; VALIDATION;
   IDENTIFICATION; METAANALYSIS; BIOMARKERS; INFERENCE; CRITERIA; PROPOSAL
AB Using multiple historical trials with surrogate and true endpoints, we consider various models to predict the effect of treatment on a true endpoint in a target trial in which only a surrogate endpoint is observed. This predicted result is computed using (1) a prediction model (mixture, linear, or principal stratification) estimated from historical trials and the surrogate endpoint of the target trial and (2) a random extrapolation error estimated from successively leaving out each trial among the historical trials. The method applies to either binary outcomes or survival to a particular time that is computed from censored survival data. We compute a 95% confidence interval for the predicted result and validate its coverage using simulation. To summarize the additional uncertainty from using a predicted instead of true result for the estimated treatment effect, we compute its multiplier of standard error. Software is available for download.
C1 [Baker, Stuart G.] NCI, Bethesda, MD 20892 USA.
   [Sargent, Daniel J.] Mayo Clin, Rochester, MN 55905 USA.
   [Buyse, Marc] IDDI, B-1340 Louvain, Belgium.
   [Burzykowski, Tomasz] Hasselt Univ, B-3590 Diepenbeek, Belgium.
RP Baker, SG (reprint author), NCI, EPN 3131,6130 Execut Blvd,MSC 7354, Bethesda, MD 20892 USA.
EM sb16i@nih.gov
OI Sargent, Daniel/0000-0002-2684-4741
FU National Cancer Institute
FX This work was supported by the National Cancer Institute. The authors
   are grateful to the MAGIC (Meta-Analysis Group in Cancer) and ACCENT
   (Adjuvant Colon Cancer Endpoints) collaborators, listed in Burzykowski
   et al. (2008), for providing the data. The authors thank the reviewers
   for helpful comments.
NR 28
TC 11
Z9 11
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0006-341X
J9 BIOMETRICS
JI Biometrics
PD MAR
PY 2012
VL 68
IS 1
BP 248
EP 257
DI 10.1111/j.1541-0420.2011.01646.x
PG 10
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
   Biology; Mathematics
GA 914BT
UT WOS:000301924400035
PM 21838732
ER

PT J
AU Caccavale, LJ
   Farhat, T
   Iannotti, RJ
AF Caccavale, Laura J.
   Farhat, Tilda
   Iannotti, Ronald J.
TI Social engagement in adolescence moderates the association between
   weight status and body image
SO BODY IMAGE
LA English
DT Article
DE Body image; Adolescents; Obesity; Social engagement
ID RISK-FACTORS; MASS INDEX; FRIENDSHIP QUALITY; INVESTMENT SCALE;
   DISSATISFACTION; OBESITY; GIRLS; HEALTH; BEHAVIORS; CHILDREN
AB This study examined whether the association between adolescent weight status and body image varies by social engagement. A nationally representative sample of 6909 students in grades 6-10 completed the 2006 HBSC survey. Separate linear regressions for boys and girls, controlling for age, race/ethnicity and socioeconomic status, were conducted with an interaction term (weight status x social engagement). Adolescents' overweight/obese status was related to body dissatisfaction. Social engagement moderated the relationship between weight status and body image for girls but not for boys. Overweight/obese boys had more body dissatisfaction compared to their normal/underweight peers, regardless of their social engagement. However, overweight/obese girls with more social engagement were more likely to have body satisfaction compared to overweight/obese girls with less social engagement. Encouraging adolescent girls to develop healthy relationships with peers may prevent them from developing body dissatisfaction. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Caccavale, Laura J.] Virginia Commonwealth Univ, Dept Psychol, Richmond, VA 23284 USA.
   [Farhat, Tilda; Iannotti, Ronald J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, NIH, Bethesda, MD USA.
RP Caccavale, LJ (reprint author), Virginia Commonwealth Univ, Dept Psychol, 806 W Franklin St,POB 842018, Richmond, VA 23284 USA.
EM caccavalelj@vcu.edu
FU Intramural NIH HHS [Z99 HD999999]; NICHD NIH HHS [N01-HD-5-3401)]
NR 46
TC 5
Z9 5
U1 2
U2 25
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1740-1445
J9 BODY IMAGE
JI Body Image
PD MAR
PY 2012
VL 9
IS 2
BP 221
EP 226
DI 10.1016/j.bodyim.2012.01.001
PG 6
WC Psychology, Clinical; Psychiatry; Psychology, Multidisciplinary
SC Psychology; Psychiatry
GA 930YP
UT WOS:000303181100005
PM 22325852
ER

PT J
AU Patel, SS
AF Patel, Sejal S.
TI Methods and Management: NIH Administrators, Federal Oversight, and the
   Framingham Heart Study
SO BULLETIN OF THE HISTORY OF MEDICINE
LA English
DT Article
DE National Institutes of Health; science administration; federal
   oversight; public administration; Framingham Heart Study; biostatistics;
   research methods; Wooldridge Review
ID WORLD-WAR-II; UNITED-STATES; EPIDEMIOLOGY; DISEASE; RISK
AB This article explores the 1965 controversy over the Framingham Heart Study in the midst of growing oversight into the management of science at the National Institutes of Health (NIH). It describes how, beginning in the early 1960s, federal overseers demanded that NIH administrators adopt particular management styles in administering programs and how these growing pressures led administrators to favor investigative pursuits that allowed for easy prospective accounting of program payoffs, especially those based on experimental methods designed to examine discrete interventions or outcomes of interest. In light of this changing managerial culture within the NIH, the Framingham study and other population laboratories-with their bases in observation and in open-ended study designs-became harder for NIH administrators to justify and defend.
RP Patel, SS (reprint author), Natl Inst Hlth, Off Hist, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [Z99 OD999999]
NR 31
TC 4
Z9 4
U1 0
U2 3
PU JOHNS HOPKINS UNIV PRESS
PI BALTIMORE
PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD
   21218-4363 USA
SN 0007-5140
J9 B HIST MED
JI Bull. Hist. Med.
PD SPR
PY 2012
VL 86
IS 1
BP 94
EP 121
PG 28
WC Health Care Sciences & Services; History & Philosophy Of Science
SC Health Care Sciences & Services; History & Philosophy of Science
GA 930YC
UT WOS:000303179700004
PM 22643985
ER

PT J
AU Sappol, M
AF Sappol, Michael
TI American Abyss: Savagery and Civilization in the Age of Industry
SO BULLETIN OF THE HISTORY OF MEDICINE
LA English
DT Book Review
C1 [Sappol, Michael] Natl Lib Med, Bethesda, MD 20894 USA.
RP Sappol, M (reprint author), Natl Lib Med, Bethesda, MD 20894 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU JOHNS HOPKINS UNIV PRESS
PI BALTIMORE
PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD
   21218-4363 USA
SN 0007-5140
J9 B HIST MED
JI Bull. Hist. Med.
PD SPR
PY 2012
VL 86
IS 1
BP 136
EP 138
PG 3
WC Health Care Sciences & Services; History & Philosophy Of Science
SC Health Care Sciences & Services; History & Philosophy of Science
GA 930YC
UT WOS:000303179700013
ER

PT J
AU Enewold, L
   Zhou, J
   McGlynn, KA
   Devesa, SS
   Shriver, CD
   Potter, JF
   Zahm, SH
   Zhu, KM
AF Enewold, Lindsey
   Zhou, Jing
   McGlynn, Katherine A.
   Devesa, Susan S.
   Shriver, Craig D.
   Potter, John F.
   Zahm, Shelia H.
   Zhu, Kangmin
TI Racial Variation in Tumor Stage at Diagnosis Among Department of Defense
   Beneficiaries
SO CANCER
LA English
DT Article
DE Department of Defense health system; military; racial disparity; tumor
   state; equal health care access
ID BREAST-CANCER MORTALITY; HEALTH-CARE-SYSTEM; AFRICAN-AMERICAN;
   UNITED-STATES; DISPARITIES; SURVIVAL; OUTCOMES; WHITE; RACE
AB BACKGROUND: Tumor stage at diagnosis often varies by racial/ethnic group, possibly because of inequitable health care access. Within the Department of Defense (DoD) Military Health System, beneficiaries have equal health care access. The objective of this study was to determine whether tumor stage differed between whites and blacks with breast, cervical, colorectal, and prostate cancers, which have effective screening regimens, based on data from the DoD Automated Cancer Tumor Registry from 1990 to 2003. METHODS: Distributions of tumor stage (localized vs nonlocalized) between whites and blacks in the military were compared stratified by sex, active duty status, and age at diagnosis. Logistic regression was used to further adjust for age, marital status, year of diagnosis, geographic region, military service branch, and tumor grade. Distributions of tumor stage were then compared between the military and general populations. RESULTS: Racial differences in the distribution of stage were significant only among nonactive duty beneficiaries. After adjusting for covariates, earlier stages of breast cancer after age 49 years and prostate cancer after age 64 years were significantly more common among white than black nonactive duty beneficiaries (P < .05), although the absolute difference was minimal for prostate cancer. Racial differences in stage for cervical and colorectal cancers were not significant after adjustment. Compared with the general population, racial differences in the military were similar or were slightly attenuated. CONCLUSIONS: Racial disparities in stage at diagnosis were apparent in the DoD equal-access health care system among older nonactive duty beneficiaries. Socioeconomic status, supplemental insurance, cultural beliefs, and biologic factors may be related to these results. Cancer 2012;118:1397-403. (C) 2011 American Cancer Society.
C1 [Enewold, Lindsey] Armed Forces Inst Pathol, US Mil Canc Inst, Walter Reed Army Med Ctr, Washington, DC 20306 USA.
   [McGlynn, Katherine A.; Devesa, Susan S.; Zahm, Shelia H.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
   [Shriver, Craig D.] Walter Reed Army Med Ctr, Dept Surg, Div Surg Oncol, Washington, DC 20307 USA.
   [Potter, John F.; Zhu, Kangmin] Uniformed Serv Univ Hlth Sci, Dept Preventat Med & Biometr, Bethesda, MD USA.
RP Enewold, L (reprint author), Armed Forces Inst Pathol, US Mil Canc Inst, Walter Reed Army Med Ctr, Bldg 54,Room N1512,6825 16th St NW, Washington, DC 20306 USA.
EM lindsey.enewold@us.army.mil
RI Zahm, Shelia/B-5025-2015
FU United States Military Cancer Institute; United States Military Cancer
   Institute through the Uniformed Services University of the Health
   Sciences; Henry M. Jackson Foundation for the Advancement of Military
   Medicine; Division of Cancer Epidemiology and Genetics, National Cancer
   Institute
FX The authors thank the Armed Forces Institute of Pathology for providing
   the Automated Cancer Tumor Registry data, especially Ms. Annette
   Anderson for coordinating the process; Dr. Hongyu Wu of the US Marine
   Corp Institute for her help in computer programming; Dr. Larry Maxwell,
   Mr. William Mahr, and Ms. Anne Dimke of the United States Military
   Cancer Institute for their support and help; and Dr. Sally Bushhouse of
   the Minnesota Cancer Surveillance System for providing the useful
   Minnesota Patient and Tumor Resolution Algorithms document.; This
   research was supported by the United States Military Cancer Institute
   through the Uniformed Services University of the Health Sciences under
   the auspices of the Henry M. Jackson Foundation for the Advancement of
   Military Medicine and by the Division of Cancer Epidemiology and
   Genetics, National Cancer Institute.
NR 30
TC 5
Z9 6
U1 1
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD MAR 1
PY 2012
VL 118
IS 5
BP 1397
EP 1403
DI 10.1002/cncr.26208
PG 7
WC Oncology
SC Oncology
GA 897QD
UT WOS:000300667800027
PM 21837685
ER

PT J
AU Cho, H
   Chung, J
   Kim, S
   Chay, D
   Hewitt, S
   Kim, J
AF Cho, H.
   Chung, J.
   Kim, S.
   Chay, D.
   Hewitt, S.
   Kim, J.
TI The expression of antiapoptotic protein API5 in cervical neoplasias
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Cho, H.; Kim, S.; Chay, D.; Kim, J.] Yonsei Univ, Coll Med, Seoul, South Korea.
   [Chung, J.; Hewitt, S.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2012
VL 125
SU 1
MA 151
BP S64
EP S64
DI 10.1016/j.ygyno.2011.12.152
PG 1
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 931NW
UT WOS:000303227600151
ER

PT J
AU Cho, H
   Chung, J
   Kim, S
   Nam, E
   Kim, S
   Kim, S
   Chay, D
   Kim, Y
   Hewitt, S
   Kim, J
AF Cho, H.
   Chung, J.
   Kim, S.
   Nam, E.
   Kim, S.
   Kim, S.
   Chay, D.
   Kim, Y.
   Hewitt, S.
   Kim, J.
TI The expression of synaptonemal complex protein 3 (SCP3) and phospho-AKT
   in cervical neoplasias
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Cho, H.; Kim, S.; Nam, E.; Kim, S.; Kim, S.; Chay, D.; Kim, Y.; Kim, J.] Yonsei Univ, Coll Med, Seoul, South Korea.
   [Chung, J.; Hewitt, S.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2012
VL 125
SU 1
MA 114
BP S49
EP S49
DI 10.1016/j.ygyno.2011.12.115
PG 1
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 931NW
UT WOS:000303227600116
ER

PT J
AU Kim, B
   Conway, C
   Kris, Y
   Hewitt, S
   Cho, H
   Kim, J
AF Kim, B.
   Conway, C.
   Kris, Y.
   Hewitt, S.
   Cho, H.
   Kim, J.
TI Influence of Nanog expression on prognosis of cervical cancer
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Kim, B.; Conway, C.; Kris, Y.; Hewitt, S.] NCI, Bethesda, MD 20892 USA.
   [Cho, H.; Kim, J.] Yonsei Univ, Coll Med, Seoul, South Korea.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2012
VL 125
SU 1
MA 147
BP S62
EP S62
DI 10.1016/j.ygyno.2011.12.148
PG 1
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 931NW
UT WOS:000303227600147
ER

PT J
AU Pothuri, B
   Sparano, J
   Blank, S
   Curtin, J
   Chuang, E
   Hershman, D
   Tiersten, A
   Liebes, L
   Chen, A
   Muggia, F
AF Pothuri, B.
   Sparano, J.
   Blank, S.
   Curtin, J.
   Chuang, E.
   Hershman, D.
   Tiersten, A.
   Liebes, L.
   Chen, A.
   Muggia, F.
TI Phase I study of the PARP inhibitor ABT-888 (veliparib) and pegylated
   liposomal doxorubicin (PLD) in recurrent ovarian (ov) and breast (br)
   cancers
SO GYNECOLOGIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Pothuri, B.; Blank, S.; Curtin, J.; Tiersten, A.; Liebes, L.; Muggia, F.] NYU, Sch Med, New York, NY USA.
   [Sparano, J.] Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA.
   [Chuang, E.] New York Presbyterian Med Ctr, New York, NY USA.
   [Hershman, D.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA.
   [Chen, A.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2012
VL 125
SU 1
MA 52
BP S22
EP S22
DI 10.1016/j.ygyno.2011.12.053
PG 1
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 931NW
UT WOS:000303227600053
ER

PT J
AU Wexler, P
   Gilbert, SG
   Thorp, N
   Faustman, E
   Breskin, DD
AF Wexler, Philip
   Gilbert, Steven G.
   Thorp, Nick
   Faustman, Elaine
   Breskin, Donna D.
TI The World Library of Toxicology, Chemical Safety, and Environmental
   Health (WLT)
SO HUMAN & EXPERIMENTAL TOXICOLOGY
LA English
DT Article
DE World Library of Toxicology; Global Toxicology Information; online
   toxicology information; wiki; IUTOX; NLM
AB The World Library of Toxicology, Chemical Safety, and Environmental Health, commonly referred to as the World Library of Toxicology (WLT), is a multilingual online portal of links to key global resources, representing a host of individual countries and multilateral organizations. The Site is designed as a network of, and gateway to, toxicological information and activities from around the world. It is built on a Wiki platform by a roster of Country Correspondents, with the aim of efficiently exchanging information and stimulating collaboration among colleagues, and building capacity, with the ultimate objective of serving as a tool to help improve global public health. The. WLT was publicly launched on September 7, 2009, at the Seventh Congress of Toxicology in Developing Countries (CTDC-VII) in Sun City, South Africa.
C1 [Wexler, Philip] US Natl Lib Med, Bethesda, MD 20894 USA.
   [Gilbert, Steven G.; Thorp, Nick] Inst Neurotoxicol & Neurol Disorders INND Toxiped, Seattle, WA USA.
   [Faustman, Elaine] Univ Washington, USA Dept Environm Hlth, Seattle, WA 98195 USA.
   [Breskin, Donna D.] IUTOX Headquarters, Int Union Toxicol, Reston, VA USA.
RP Wexler, P (reprint author), US Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM wexlerp@mail.nih.gov
OI Faustman, Elaine/0000-0002-3085-6403
NR 3
TC 2
Z9 2
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0960-3271
J9 HUM EXP TOXICOL
JI Hum. Exp. Toxicol.
PD MAR
PY 2012
VL 31
IS 3
SI SI
BP 207
EP 214
DI 10.1177/0960327110389500
PG 8
WC Toxicology
SC Toxicology
GA 928ZF
UT WOS:000303030300002
PM 21071551
ER

PT J
AU Kim, HK
   Chanock, SJ
AF Kim, Hye Kyung
   Chanock, Stephen J.
TI Genome-wide association studies in melanoma: off to a good start
SO PIGMENT CELL & MELANOMA RESEARCH
LA English
DT Article
ID BASAL-CELL CARCINOMA; CUTANEOUS MELANOMA; SEQUENCE VARIANTS;
   BREAST-CANCER; IDENTIFIES 3; RISK; SUSCEPTIBILITY; LOCI; GENE;
   HERITABILITY
C1 [Kim, Hye Kyung; Chanock, Stephen J.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA.
RP Kim, HK (reprint author), NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA.
EM chanocks@mail.nih.gov
NR 20
TC 0
Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1755-1471
J9 PIGM CELL MELANOMA R
JI Pigment Cell Melanoma Res.
PD MAR
PY 2012
VL 25
IS 2
DI 10.1111/j.1755-148X.2012.00981.x
PG 4
WC Oncology; Cell Biology; Dermatology
SC Oncology; Cell Biology; Dermatology
GA 897UK
UT WOS:000300683200016
PM 22268896
ER

PT J
AU Walia, V
   Mu, EW
   Lin, JC
   Samuels, Y
AF Walia, Vijay
   Mu, Euphemia W.
   Lin, Jimmy C.
   Samuels, Yardena
TI Delving into somatic variation in sporadic melanoma
SO PIGMENT CELL & MELANOMA RESEARCH
LA English
DT Review
DE melanoma; somatic mutation; sequencing
ID KIT PROTEIN EXPRESSION; MALIGNANT-MELANOMA; ULTRAVIOLET-RADIATION;
   METASTATIC MELANOMA; HUMAN CANCER; MATRIX METALLOPROTEINASES; GENOMIC
   ANALYSES; RENAL-CARCINOMA; UVEAL MELANOMA; HUMAN BREAST
AB Melanoma, the most aggressive form of skin cancer, has increased in incidence more rapidly than any other cancer. The completion of the human genome project and advancements in genomics technologies has allowed us to investigate genetic alterations of melanoma at a scale and depth that is unprecedented. Here, we survey the history of the different approaches taken to understand the genomics of melanoma from early candidate genes, to gene families, to genome-wide studies. The new era of whole-exome and whole-genome sequencing has paved the way for an in-depth understanding of melanoma biology, identification of new therapeutic targets, and development of novel personalized therapies for melanoma.
C1 [Walia, Vijay; Samuels, Yardena] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
   [Mu, Euphemia W.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
   [Lin, Jimmy C.] Washington Univ, Sch Med, Dept Pathol & Immunol, Div Lab & Genom Med, St Louis, MO USA.
RP Samuels, Y (reprint author), NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
EM samuelsy@mail.nih.gov
RI Walia, Vijay/F-1647-2013
FU National Human Genome Research Institute, National Institutes of Health,
   USA
FX We thank Mike Davies and Jared Gartner for insightful comments. This
   work was supported by the Intramural Research Programs of the National
   Human Genome Research Institute, National Institutes of Health, USA.
NR 139
TC 22
Z9 22
U1 1
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1755-1471
J9 PIGM CELL MELANOMA R
JI Pigment Cell Melanoma Res.
PD MAR
PY 2012
VL 25
IS 2
DI 10.1111/j.1755-148X.2012.00976.x
PG 17
WC Oncology; Cell Biology; Dermatology
SC Oncology; Cell Biology; Dermatology
GA 897UK
UT WOS:000300683200009
PM 22260482
ER

PT J
AU Yang, XR
   Brown, K
   Landi, MT
   Ghiorzo, P
   Badenas, C
   Xu, M
   Hayward, NK
   Calista, D
   Landi, G
   Bruno, W
   Bianchi-Scarra, G
   Aguilera, P
   Puig, S
   Goldstein, AM
   Tucker, MA
AF Yang, Xiaohong R.
   Brown, Kevin
   Landi, Maria T.
   Ghiorzo, Paola
   Badenas, Celia
   Xu, Mai
   Hayward, Nicholas K.
   Calista, Donato
   Landi, Giorgio
   Bruno, William
   Bianchi-Scarra, Giovanna
   Aguilera, Paula
   Puig, Susana
   Goldstein, Alisa M.
   Tucker, Margaret A.
TI Duplication of CXC chemokine genes on chromosome 4q13 in a
   melanoma-prone family
SO PIGMENT CELL & MELANOMA RESEARCH
LA English
DT Article
DE familial melanoma; germline copy number variations; disease
   susceptibility; CXC chemokines; chromosome 4q13
ID EXPRESSION; GROWTH; INTERLEUKIN-8; PROGRESSION; CELLS
AB Copy number variations (CNVs) have been shown to contribute substantially to disease susceptibility in several inherited diseases including cancer. We conducted a genome-wide search for CNVs in blood-derived DNA from 79 individuals (62 melanoma patients and 17 spouse controls) of 30 high-risk melanoma-prone families without known segregating mutations using genome-wide comparative genomic hybridization (CGH) tiling arrays. We identified a duplicated region on chromosome 4q13 in germline DNA of all melanoma patients in a melanoma-prone family with three affected siblings. We confirmed the duplication using quantitative PCR and a custom-made CGH array design spanning the 4q13 region. The duplicated region contains 10 genes, most of which encode CXC chemokines. Among them, CXCL1 (melanoma growth-stimulating activity a) and IL8 (interleukin 8) have been shown to stimulate melanoma growth in vitro and in vivo. Our data suggest that the alteration of CXC chemokine genes may confer susceptibility to melanoma.
C1 [Yang, Xiaohong R.; Brown, Kevin; Landi, Maria T.; Xu, Mai; Goldstein, Alisa M.; Tucker, Margaret A.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
   [Ghiorzo, Paola; Bruno, William; Bianchi-Scarra, Giovanna] Univ Genoa, DOBIG, Dept Oncol Biol & Genet, Genoa, Italy.
   [Badenas, Celia] Hosp Clin Barcelona, Dept Biochem & Mol Genet, IDIBAPS, Barcelona, Spain.
   [Hayward, Nicholas K.] Queensland Inst Med Res, Oncogen Lab, Brisbane, Qld 4006, Australia.
   [Calista, Donato; Landi, Giorgio] Maurizio Bufalini Hosp, Cesena, Italy.
   [Bianchi-Scarra, Giovanna] San Martino Hosp, Lab Genet Rare Hereditary Canc, Genoa, Italy.
   [Aguilera, Paula; Puig, Susana] Hosp Clin Barcelona, Dept Dermatol, Melanoma Unit, IDIBAPS, Barcelona, Spain.
   [Puig, Susana] Inst Salud Carlos III, CIBER Enfermedades Raras, Barcelona, Spain.
RP Yang, XR (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
EM royang@mail.nih.gov
RI Bianchi Scarra, Giovanna/G-8933-2014; Tucker, Margaret/B-4297-2015;
   hayward, nicholas/C-1367-2015; Bruno, William/N-7477-2013; 
OI Bianchi Scarra, Giovanna/0000-0002-6127-1192; hayward,
   nicholas/0000-0003-4760-1033; Bruno, William/0000-0002-0337-0168;
   Badenas, Celia/0000-0002-0621-0477; Puig, Susana/0000-0003-1337-9745
FU NIH; NCI; DCEG; Fondo de Investigaciones Sanitarias, Spain [06/0265,
   09/1393]; CIBER de Enfermedades Raras of the Instituto de Salud Carlos
   III, Spain; AGAUR of Catalan Government, Spain [SGR 1337]; European
   Commission [LSHC-CT-2006-018702]; National Cancer Institute (NCI) of the
   US National Institute of Health (NIH) [CA83115]; Fondo de
   Investigaciones Sanitarias, Instituto de Salud Carlos III [Rio Hortega
   10/00120]; Fondazione CARIGE; IMI and ACM; Italian Ministry of Health
   [DGRST.4/4235-P1.9.A.B]; National Health and Medical Research Council of
   Australia
FX We are indebted to the participating families, whose generosity and
   cooperation have made this study possible. We thank Seq-Wright, Roche
   Nimblegen, and Biodiscovery for their molecular and informatic services.
   We also acknowledge the contributions to this work that were made by
   Virginia Pichler, Deborah Zametkin, Mary Fraser, and Barbara Rogers.
   This research was supported by the Intramural Research Program of the
   NIH, NCI, DCEG. The research at the Melanoma Unit in Barcelona is
   partially funded by Grants 06/0265 and 09/1393 from Fondo de
   Investigaciones Sanitarias, Spain; by the CIBER de Enfermedades Raras of
   the Instituto de Salud Carlos III, Spain; by the AGAUR 2009 SGR 1337 of
   the Catalan Government, Spain; by the European Commission under the 6th
   Framework Programme, Contract nr: LSHC-CT-2006-018702 (GenoMEL); and by
   the National Cancer Institute (NCI) of the US National Institute of
   Health (NIH) (CA83115) and a personal grant to Paula Aguilera from Fondo
   de Investigaciones Sanitarias, Instituto de Salud Carlos III, Rio
   Hortega 10/00120. Genoa team research has been supported by: Fondazione
   CARIGE 2010, IMI and ACM 2011, Italian Ministry of Health
   DGRST.4/4235-P1.9.A.B. NKH is supported by a Senior Principal Research
   Fellowship from the National Health and Medical Research Council of
   Australia.
NR 16
TC 6
Z9 7
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1755-1471
J9 PIGM CELL MELANOMA R
JI Pigment Cell Melanoma Res.
PD MAR
PY 2012
VL 25
IS 2
DI 10.1111/j.1755-148X.2012.00969.x
PG 6
WC Oncology; Cell Biology; Dermatology
SC Oncology; Cell Biology; Dermatology
GA 897UK
UT WOS:000300683200018
PM 22225770
ER

PT J
AU Venkova-Canova, T
   Saha, A
   Chattoraj, DK
AF Venkova-Canova, Tatiana
   Saha, Anik
   Chattoraj, Dhruba K.
TI A 29-mer site regulates transcription of the initiator gene as well as
   function of the replication origin of Vibrio cholerae chromosome II
SO PLASMID
LA English
DT Article
DE Vibrio cholerae; Secondary chromosome; Transcriptional autorepression;
   Operator site; Replication control; Hetero-handcuffing
ID P1 PLASMID REPLICATION; ESCHERICHIA-COLI; DNA-REPLICATION; CELL-CYCLE;
   SEQUENCE; RCTB; INACTIVATION; SEGREGATION; METHYLATION; PROTEIN
AB The region responsible for replication of Vibrio cholerae chromosome II (chrII) resembles those of plasmids that have repeated initiator binding sites (iterons) and an autorepressed initiator gene. ChrII has additional features: Its iterons require full methylation for initiator (RctB) binding, which makes them inactive for a part of the cell cycle when they are hemimethylated. RctB also binds to a second kind of site, called 39-mers, in a methylation independent manner. This binding is inhibitory to chrII replication. The site that RctB uses for autorepression has not been identified. Here we show that a 29-mer sequence, similar to the 39-mers, serves as that site, as we find that it binds RctB in vitro and suffices to repress the rctB promoter in vivo. The site is not subject to methylation and is likely to be active throughout the cell cycle. The 29-mer, like the 39-mers, could inhibit RctB-dependent mini-chrII replication in Escherichia coli, possibly by coupling with iterons via RctB bridges, as was seen in vitro. The 29-mer thus appears to play a dual role in regulating chrII replication: one independent of the cell cycle, the other dependent upon iteron methylation, hence responsive to the cell cycle. Published by Elsevier Inc.
C1 [Venkova-Canova, Tatiana; Saha, Anik; Chattoraj, Dhruba K.] NCI, Lab Biochem & Mol Biol, NIH, Bethesda, MD 20892 USA.
RP Venkova-Canova, T (reprint author), NCI, Lab Biochem & Mol Biol, NIH, 37 Convent Dr,Room 6044, Bethesda, MD 20892 USA.
EM canovat@mail.nih.gov
FU Center for Cancer Research, National Cancer Institute
FX We thank Arnab Sarkar and Souvanik Adhya, for plasmid construction. We
   are grateful to Michael Yarmolinsky for a critical review of an earlier
   draft of this paper. This work was supported by the Intramural Research
   Program, Center for Cancer Research, National Cancer Institute.
NR 30
TC 9
Z9 9
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 0147-619X
J9 PLASMID
JI Plasmid
PD MAR
PY 2012
VL 67
IS 2
SI SI
BP 102
EP 110
DI 10.1016/j.plasmid.2011.12.009
PG 9
WC Genetics & Heredity; Microbiology
SC Genetics & Heredity; Microbiology
GA 932RG
UT WOS:000303307600006
PM 22248922
ER

PT J
AU Sawitzke, JA
   Youngren, B
   Thomason, LC
   Baker, T
   Sengupta, M
   Court, D
   Austin, S
AF Sawitzke, James A.
   Youngren, Brenda
   Thomason, Lynn C.
   Baker, Teresa
   Sengupta, Manjistha
   Court, Donald
   Austin, Stuart
TI The segregation of Escherichia coli minichromosomes constructed in vivo
   by recombineering
SO PLASMID
LA English
DT Article
DE Recombineering; Minichromosomes; oriC plasmids; Segregation;
   Localization
ID HOMOLOGOUS RECOMBINATION; CHROMOSOME SEGREGATION; REPLICATION; ORIGIN;
   PLASMIDS; ABSENCE; SYSTEM
AB Circularized regions of the chromosome containing the origin of replication, oriC, can be maintained as autonomous minichromosomes, oriC plasmids. We show that oriC plasmids containing precise, pre-determined segments of the chromosome can be generated by a simple in vivo recombineering technique. We generated two such plasmids carrying fluorescent markers. These were transferred to a recipient strain with a different fluorescent marker near the chromosomal copy of oriC. Thus the fates of the oriC plasmid and chromosomal origins could be followed independently in living cells by fluorescence microscopy. In contrast to a previous report, we show that there is a strong tendency of oriC plasmid copies to accumulate at the cell center as a single or double focus at the plane of cell division. This is not simply due to exclusion from the nucleoid space but rather appears to be a specific recognition and retention of the plasmid by some central-located cell site. Published by Elsevier Inc.
C1 [Sawitzke, James A.; Youngren, Brenda; Baker, Teresa; Sengupta, Manjistha; Court, Donald; Austin, Stuart] NCI, Gene Regulat & Chromosome Biol Lab, CCR, Frederick, MD 21702 USA.
   [Thomason, Lynn C.] SAIC Frederick Inc, Gene Regulat & Chromosome Biol Lab, Basic Res Program, Frederick, MD USA.
RP Austin, S (reprint author), NCI, Gene Regulat & Chromosome Biol Lab, CCR, Frederick, MD 21702 USA.
EM austin@ncifcrf.gov
FU National Cancer Institute, National Institutes of Health
   [HHSN26120080001E]; NIH, National Cancer Institute, Center for Cancer
   Research
FX The project has been funded 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 US Government. This research was
   supported in part by the Intramural Research Program of the NIH,
   National Cancer Institute, Center for Cancer Research.
NR 19
TC 0
Z9 0
U1 0
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0147-619X
J9 PLASMID
JI Plasmid
PD MAR
PY 2012
VL 67
IS 2
SI SI
BP 148
EP 154
DI 10.1016/j.plasmid.2012.01.002
PG 7
WC Genetics & Heredity; Microbiology
SC Genetics & Heredity; Microbiology
GA 932RG
UT WOS:000303307600011
PM 22252137
ER

PT J
AU Shakeri, R
   Kamangar, F
   Nasrollahzadeh, D
   Nouraie, M
   Khademi, H
   Etemadi, A
   Islami, F
   Marjani, H
   Fahimi, S
   Sepehr, A
   Rahmati, A
   Abnet, CC
   Dawsey, SM
   Brennan, P
   Boffetta, P
   Malekzadeh, R
   Majdzadeh, R
AF Shakeri, Ramin
   Kamangar, Farin
   Nasrollahzadeh, Dariush
   Nouraie, Mehdi
   Khademi, Hooman
   Etemadi, Arash
   Islami, Farhad
   Marjani, Hajiamin
   Fahimi, Saman
   Sepehr, Alireza
   Rahmati, Atieh
   Abnet, Christian C.
   Dawsey, Sanford M.
   Brennan, Paul
   Boffetta, Paolo
   Malekzadeh, Reza
   Majdzadeh, Reza
TI Is Opium a Real Risk Factor for Esophageal Cancer or Just a
   Methodological Artifact? Hospital and Neighborhood Controls in
   Case-Control Studies
SO PLOS ONE
LA English
DT Article
ID POPULATION-CONTROLS; GOLESTAN COHORT; NORTHERN IRAN; ALCOHOL; SELECTION;
   QUESTION; TOBACCO; TRACT; AREA; DIET
AB Background: Control selection is a major challenge in epidemiologic case-control studies. The aim of our study was to evaluate using hospital versus neighborhood control groups in studying risk factors of esophageal squamous cell carcinoma (ESCC).
   Methodology/Principal Findings: We compared the results of two different case-control studies of ESCC conducted in the same region by a single research group. Case definition and enrollment were the same in the two studies, but control selection differed. In the first study, we selected two age-and sex-matched controls from inpatient subjects in hospitals, while for the second we selected two age-and sex-matched controls from each subject's neighborhood of residence. We used the test of heterogeneity to compare the results of the two studies. We found no significant differences in exposure data for tobacco-related variables such as cigarette smoking, chewing Nass (a tobacco product) and hookah (water pipe) usage, but the frequency of opium usage was significantly different between hospital and neighborhood controls. Consequently, the inference drawn for the association between ESCC and tobacco use did not differ between the studies, but it did for opium use. In the study using neighborhood controls, opium use was associated with a significantly increased risk of ESCC (adjusted OR 1.77, 95% CI 1.17-2.68), while in the study using hospital controls, this was not the case (OR 1.09, 95% CI 0.63-1.87). Comparing the prevalence of opium consumption in the two control groups and a cohort enrolled from the same geographic area suggested that the neighborhood controls were more representative of the study base population for this exposure.
   Conclusions/Significance: Hospital and neighborhood controls did not lead us to the same conclusion for a major hypothesized risk factor for ESCC in this population. Our results show that control group selection is critical in drawing appropriate conclusions in observational studies.
C1 [Shakeri, Ramin; Kamangar, Farin; Nasrollahzadeh, Dariush; Nouraie, Mehdi; Khademi, Hooman; Etemadi, Arash; Islami, Farhad; Marjani, Hajiamin; Fahimi, Saman; Sepehr, Alireza; Rahmati, Atieh; Malekzadeh, Reza] Univ Tehran Med Sci, Shariati Hosp, Digest Dis Res Ctr, Tehran, Iran.
   [Shakeri, Ramin; Kamangar, Farin; Etemadi, Arash; Abnet, Christian C.; Dawsey, Sanford M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Kamangar, Farin] Morgan State Univ, Sch Community Hlth & Policy, Dept Publ Hlth Anal, Baltimore, MD 21239 USA.
   [Nasrollahzadeh, Dariush] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
   [Nouraie, Mehdi] Howard Univ, Dept Internal Med, Washington, DC 20059 USA.
   [Nouraie, Mehdi] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA.
   [Khademi, Hooman; Islami, Farhad; Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France.
   [Fahimi, Saman] Univ Cambridge, Cambridge, England.
   [Sepehr, Alireza] Harvard Univ, Sch Med, Dept Pathol, BIDMC, Boston, MA 02115 USA.
   [Rahmati, Atieh] Univ Tehran Med Sci, Firoozgar Hosp, Gastrointestinal & Liver Dis Res Ctr, Tehran, Iran.
   [Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA.
   [Boffetta, Paolo] Int Prevent Res Inst, Lyon, France.
   [Majdzadeh, Reza] Univ Tehran Med Sci, Sch Publ Hlth, Dept Epidemiol & Biostat, Tehran, Iran.
   [Majdzadeh, Reza] Univ Tehran Med Sci, Knowledge Utilizat Res Ctr, Tehran, Iran.
RP Shakeri, R (reprint author), Univ Tehran Med Sci, Shariati Hosp, Digest Dis Res Ctr, Tehran, Iran.
EM rezamajd@tums.ac.ir
RI Abnet, Christian/C-4111-2015; Etemadi, Arash/C-1386-2016; 
OI Abnet, Christian/0000-0002-3008-7843; Etemadi,
   Arash/0000-0002-3458-1072; , Ramin/0000-0003-0487-3629; Malekzadeh,
   Reza/0000-0003-1043-3814
NR 23
TC 8
Z9 8
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 MAR 1
PY 2012
VL 7
IS 3
AR e32711
DI 10.1371/journal.pone.0032711
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 928SU
UT WOS:000303005000036
PM 22396792
ER

PT J
AU Wagner, S
   Zensi, A
   Wien, SL
   Tschickardt, SE
   Maier, W
   Vogel, T
   Worek, F
   Pietrzik, CU
   Kreuter, J
   von Briesen, H
AF Wagner, Sylvia
   Zensi, Anja
   Wien, Sascha L.
   Tschickardt, Sabrina E.
   Maier, Wladislaw
   Vogel, Tikva
   Worek, Franz
   Pietrzik, Claus U.
   Kreuter, Joerg
   von Briesen, Hagen
TI Uptake Mechanism of ApoE-Modified Nanoparticles on Brain Capillary
   Endothelial Cells as a Blood-Brain Barrier Model
SO PLOS ONE
LA English
DT Article
ID RECEPTOR-RELATED PROTEIN; E-DERIVED PEPTIDE; 80-COATED
   POLYBUTYLCYANOACRYLATE NANOPARTICLES; PEGYLATED POLYCYANOACRYLATE
   NANOPARTICLES; POLY(BUTYL CYANOACRYLATE) NANOPARTICLES;
   APOLIPOPROTEIN-A-I; DRUG-DELIVERY; ELECTRICAL-RESISTANCE; DESOLVATION
   PROCESS; HSA-NANOPARTICLES
AB Background: The blood-brain barrier (BBB) represents an insurmountable obstacle for most drugs thus obstructing an effective treatment of many brain diseases. One solution for overcoming this barrier is a transport by binding of these drugs to surface-modified nanoparticles. Especially apolipoprotein E (ApoE) appears to play a major role in the nanoparticle-mediated drug transport across the BBB. However, at present the underlying mechanism is incompletely understood.
   Methodology/Principal Findings: In this study, the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells was investigated to differentiate between active and passive uptake mechanism by flow cytometry and confocal laser scanning microscopy. Furthermore, different in vitro co-incubation experiments were performed with competing ligands of the respective receptor.
   Conclusions/Significance: This study confirms an active endocytotic uptake mechanism and shows the involvement of low density lipoprotein receptor family members, notably the low density lipoprotein receptor related protein, on the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells. This knowledge of the uptake mechanism of ApoE-modified nanoparticles enables future developments to rationally create very specific and effective carriers to overcome the blood-brain barrier.
C1 [Wagner, Sylvia; Wien, Sascha L.; von Briesen, Hagen] Fraunhofer Inst Biomed Engn, Dept Cell Biol & Appl Virol, St Ingbert, Germany.
   [Zensi, Anja; Kreuter, Joerg] Goethe Univ Frankfurt, Inst Pharmaceut Technol, Frankfurt, Germany.
   [Tschickardt, Sabrina E.; Maier, Wladislaw; Pietrzik, Claus U.] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Pathobiochem, Mainz, Germany.
   [Vogel, Tikva] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
   [Vogel, Tikva] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA.
   [Worek, Franz] Bundeswehr Inst Pharmacol & Toxicol, Munich, Germany.
RP Wagner, S (reprint author), Fraunhofer Inst Biomed Engn, Dept Cell Biol & Appl Virol, St Ingbert, Germany.
EM hagen.briesen@ibmt.fraunhofer.de
RI Fachbereich14, Dekanat/C-8553-2015; 
OI Worek, Franz/0000-0003-3531-3616
FU German Bundesministerium fur Bildung und Forschung (BMBF) [01EW1009,
   01EW1010]; Deutsche Bundesamt fur Wehrtechnik und Beschaffung [U2.3
   E/UR3G/5G031/5A802]
FX This work was financially supported by the German Bundesministerium fur
   Bildung und Forschung (BMBF) (01EW1009, 01EW1010) and by the Deutsche
   Bundesamt fur Wehrtechnik und Beschaffung (U2.3 E/UR3G/5G031/5A802). The
   funders had no role in study design, data collection and analysis,
   decision to publish, or preparation of the manuscript.
NR 52
TC 60
Z9 61
U1 1
U2 26
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 MAR 1
PY 2012
VL 7
IS 3
AR e32568
DI 10.1371/journal.pone.0032568
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 928SU
UT WOS:000303005000029
PM 22396775
ER

PT J
AU Kwintkiewicz, J
   Padilla-Banks, E
   Jefferson, WN
   Jacobs, IM
   Wade, PA
   Williams, CJ
AF Kwintkiewicz, Jakub
   Padilla-Banks, Elizabeth
   Jefferson, Wendy N.
   Jacobs, Ilana M.
   Wade, Paul A.
   Williams, Carmen J.
TI Metastasis-Associated Protein 3 (MTA3) Regulates G2/M Progression in
   Proliferating Mouse Granulosa Cells
SO BIOLOGY OF REPRODUCTION
LA English
DT Article
DE cell cycle; chromatin; cohesin; granulosa cells; NuRD complex; ovary
ID CHROMATIN-REMODELING COMPLEX; HISTONE DEACETYLASE ACTIVITY; DNA-DAMAGE;
   MI-2/NURD COMPLEX; CYCLE PROGRESSION; OVARIAN-FOLLICLE; GENE-EXPRESSION;
   FACTOR CHD4; AURORA-B; COHESIN
AB Metastasis-associated protein 3 (MTA3) is a constituent of the Mi-2/nucleosome remodeling and deacetylase (NuRD) protein complex that regulates gene expression by altering chromatin structure and can facilitate cohesin loading onto DNA. The biological function of MTA3 within the NuRD complex is unknown. Herein, we show that MTA3 was expressed highly in granulosa cell nuclei of all ovarian follicle stages and at lower levels in corpora lutea. We tested the hypothesis that MTA3-NuRD complex function is required for granulosa cell proliferation. In the ovary, MTA3 interacted with NuRD proteins CHD4 and HDAC1 and the core cohesin complex protein RAD21. In cultured mouse primary granulosa cells, depletion of endogenous MTA3 using RNA interference slowed cell proliferation; this effect was rescued by coexpression of exogenous MTA3. Slowing of cell proliferation correlated with a significant decrease in cyclin B1 and cyclin B2 expression. Granulosa cell populations lacking MTA3 contained a significantly higher percentage of cells in G2/M phase and a lower percentage in S phase compared with control cells. Furthermore, MTA3 depletion slowed entry into M phase as indicated by reduced phosphorylation of histone H3 at serine 10. These findings provide the first evidence to date that MTA3 interacts with NuRD and cohesin complex proteins in the ovary in vivo and regulates G2/M progression in proliferating granulosa cells.
C1 [Kwintkiewicz, Jakub; Padilla-Banks, Elizabeth; Jefferson, Wendy N.; Jacobs, Ilana M.; Williams, Carmen J.] NIEHS, Reprod Med Grp, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA.
   [Wade, Paul A.] NIEHS, Eukaryot Transcript Regulat Grp, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Williams, CJ (reprint author), NIEHS, Reprod Med Grp, Lab Reprod & Dev Toxicol, NIH, POB 12233,MD E4-05, Res Triangle Pk, NC 27709 USA.
EM williamsc5@niehs.nih.gov
RI Williams, Carmen/E-2170-2013
OI Williams, Carmen/0000-0001-6440-7086
FU National Institute of Environmental Health Sciences, National Institutes
   of Health [Z01-ES102985, Z01-ES101965]
FX Supported by grants Z01-ES102985, and Z01-ES101965 from the National
   Institute of Environmental Health Sciences, Intramural Research Program
   of the National Institutes of Health.
NR 45
TC 3
Z9 3
U1 0
U2 4
PU SOC STUDY REPRODUCTION
PI MADISON
PA 1603 MONROE ST, MADISON, WI 53711-2021 USA
SN 0006-3363
J9 BIOL REPROD
JI Biol. Reprod.
PD MAR
PY 2012
VL 86
IS 3
AR 64
DI 10.1095/biolreprod.111.096032
PG 8
WC Reproductive Biology
SC Reproductive Biology
GA 916SL
UT WOS:000302123400004
PM 22075476
ER

PT J
AU Vyas, VV
   Esposito, D
   Sumpter, TL
   Broadt, TL
   Hartley, J
   Knapp, GC
   Cheng, W
   Jiang, MS
   Roach, JM
   Yang, XY
   Giardina, SL
   Mitra, G
   Yovandich, JL
   Creekmore, SP
   Waldmann, TA
   Zhu, JW
AF Vyas, Vinay V.
   Esposito, Dominic
   Sumpter, Terry L.
   Broadt, Trevor L.
   Hartley, James
   Knapp, George C.
   Cheng, Wei
   Jiang, Man-Shiow
   Roach, John M.
   Yang, Xiaoyi
   Giardina, Steven L.
   Mitra, George
   Yovandich, Jason L.
   Creekmore, Stephen P.
   Waldmann, Thomas A.
   Zhu, Jianwei
TI Clinical manufacturing of recombinant human interleukin 15. I.
   Production cell line development and protein expression in E. coli with
   stop codon optimization
SO BIOTECHNOLOGY PROGRESS
LA English
DT Article
DE interleukin 15; protein expression; stop codon; clinical manufacturing;
   E; coli
ID CD8(+) T-CELLS; IN-VIVO; IL-15; READTHROUGH; TERMINATION; RECEPTOR;
   SIGNAL; PROLIFERATION; IMMUNOTHERAPY; SUPPRESSION
AB Interleukin 15 (IL-15) has shown remarkable biological properties of promoting NK- and T-cell activation and proliferation, as well as enhancing antitumor immunity of CD8+ T cells in preclinical models. Here, we report the development of an E. coli cell line to express recombinant human Interleukin-15 (rhIL-15) for clinical manufacturing. Human IL-15 cDNA sequence was inserted into a pET28b plasmid and expressed in several E. coli BL21 strains. Through product quality comparisons among several E. coli strains, including E. coli BL21(DE3), BL21(DE3)pLysS, BLR(DE3)pLysS, and BL21-AI, E. coli BL21-AI was selected for clinical manufacturing. Expression optimization was carried out at shake flask and 20-L fermenter scales, and the product was expressed as inclusion bodies that were solubilized, refolded, and purified to yield active rhIL-15. Stop codons of the expression construct were further investigated after 1520% of the purified rhIL-15 showed an extraneous peak corresponding to an extra tryptophan residue based on peptide mapping and mass spectrometry analysis. It was determined that the presence of an extra tryptophan was due to a stop codon wobble effect, which could be eliminated by replacing TGA (opal) stop codon with TAA (ochre). As a novel strategy, a simple method of demonstrating lack of tRNA suppressors in the production host cells was developed to validate the cells in this study. The E. coli BL21-AI cells containing the rhIL-15 coding sequence with a triplet stop codon TAATAATGA were banked for further clinical manufacturing. (c) 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2012
C1 [Vyas, Vinay V.; Sumpter, Terry L.; Broadt, Trevor L.; Knapp, George C.; Cheng, Wei; Jiang, Man-Shiow; Roach, John M.; Yang, Xiaoyi; Giardina, Steven L.; Mitra, George; Zhu, Jianwei] NCI, Biopharmaceut Dev Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
   [Esposito, Dominic; Hartley, James; Yovandich, Jason L.; Creekmore, Stephen P.] NCI, Protein Express Lab, Adv Technol Program, SAIC Frederick, Frederick, MD 21702 USA.
   [Waldmann, Thomas A.] NCI, Ctr Canc Res, Metab Branch, Bethesda, MD 20892 USA.
RP Zhu, JW (reprint author), NCI, Biopharmaceut Dev Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
EM zhujianwei@mail.nih.gov
FU National Cancer Institute, National Institutes of Health [N01-CO-12400,
   HHSN261200800001E]
FX This project has been funded in whole or in part with federal funds from
   the National Cancer Institute, National Institutes of Health, under
   contracts N01-CO-12400 and #HHSN261200800001E. The content of this
   publication does not necessarily reflect the views or policies of the
   Department of Health and Human Services, nor does the mentioning of
   trade names, commercial products, or organizations imply endorsement by
   the U.S. government.
NR 32
TC 2
Z9 3
U1 4
U2 14
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 8756-7938
J9 BIOTECHNOL PROGR
JI Biotechnol. Prog.
PD MAR-APR
PY 2012
VL 28
IS 2
BP 497
EP 507
DI 10.1002/btpr.746
PG 11
WC Biotechnology & Applied Microbiology; Food Science & Technology
SC Biotechnology & Applied Microbiology; Food Science & Technology
GA 923GH
UT WOS:000302607100024
PM 22162520
ER

PT J
AU Lisnyy, I
   Stahovskiy, E
   Kuchin, Y
   Klimchuk, L
AF Lisnyy, Ivan
   Stahovskiy, Eduard
   Kuchin, Yuryy
   Klimchuk, Ludmila
TI Postoperative pain and pge2 after preemptive analgesia with
   dexketoprofen. A randomized double blind placebo controlled study
SO BRITISH JOURNAL OF ANAESTHESIA
LA English
DT Meeting Abstract
CT 15th World-Federation-of-Societies-of-Anaesthesiologists (WFSA) World
   Congress of Anaesthesiologists
CY MAR 25-30, 2012
CL Buenos Aires, ARGENTINA
SP World Federat Soc Anaesthesiol (WFSA)
C1 [Lisnyy, Ivan; Klimchuk, Ludmila] NCI, Dept Anesthesiol, Bethesda, MD 20892 USA.
   [Stahovskiy, Eduard] NCI, Oncourol Dept, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0007-0912
J9 BRIT J ANAESTH
JI Br. J. Anaesth.
PD MAR
PY 2012
VL 108
SU 2
BP 401
EP 401
PG 1
WC Anesthesiology
SC Anesthesiology
GA 919CT
UT WOS:000302299100675
ER

PT J
AU Mueller, SC
   Hardin, MG
   Korelitz, K
   Daniele, T
   Bemis, J
   Dozier, M
   Peloso, E
   Maheu, FS
   Pine, DS
   Ernst, M
AF Mueller, Sven C.
   Hardin, Michael G.
   Korelitz, Katherine
   Daniele, Teresa
   Bemis, Jessica
   Dozier, Mary
   Peloso, Elizabeth
   Maheu, Francoise S.
   Pine, Daniel S.
   Ernst, Monique
TI Incentive effect on inhibitory control in adolescents with early-life
   stress: An antisaccade study
SO CHILD ABUSE & NEGLECT
LA English
DT Article
DE Reward; Antisaccade; Cognitive control; Early adversity; Stress
ID COGNITIVE CONTROL; EARLY DEPRIVATION; EYE-MOVEMENT; CHILDHOOD
   MALTREATMENT; DEPRESSED ADOLESCENTS; BRAIN-FUNCTION; SACCADE TASK;
   CHILDREN; HEALTHY; REWARD
AB Objective: Early-life stress (ES) such as adoption, change of caregiver, or experience of emotional neglect may influence the way in which affected individuals respond to emotional stimuli of positive or negative valence. These modified responses may stem from a direct alteration of how emotional stimuli are coded, and/or the cognitive function implicated in emotion modulation, such as self-regulation or inhibition. These ES effects have been probed on tasks either targeting reward and inhibitory function. Findings revealed deficits in both reward processing and inhibitory control in ES youths. However, no work has yet examined whether incentives can improve automatic response or inhibitory control in ES youths.
   Method: To determine whether incentives would only improve self-regulated voluntary actions or generalize to automated motoric responses, participants were tested on a mixed eye movement task that included reflex-like prosaccades and voluntary controlled antisaccade eye movements. Seventeen adopted children (10 females, mean age 11.3 years) with a documented history of neglect and 29 typical healthy youths (16 females, mean age 11.9 years) performed the mixed prosaccade/antisaccade task during monetary incentive conditions or during no-incentive conditions.
   Results: Across both saccade types, ES adolescents responded more slowly than controls. As expected, control participants committed fewer errors on antisaccades during the monetary incentive condition relative to the no-incentive condition. By contrast, ES youths failed to show this incentive-related improvement on inhibitory control. No significant incentive effects were found with prepotent prosaccades trials in either group. Finally co-morbid psychopathology did not modulate the findings.
   Conclusions: These data suggest that youths with experience of early stress exhibit deficient modulation of inhibitory control by reward processes, in tandem with a reward-independent deficit in preparation for both automatic and controlled responses. These data may be relevant to interventions in ES youths. Published by Elsevier Ltd.
C1 [Mueller, Sven C.; Korelitz, Katherine; Daniele, Teresa; Bemis, Jessica; Pine, Daniel S.; Ernst, Monique] NIMH, Sect Dev & Affect Neurosci, NIH, Bethesda, MD 20892 USA.
   [Mueller, Sven C.] Univ Ghent, Dept Expt Clin & Hlth Psychol, Ghent, Belgium.
   [Hardin, Michael G.] Stanford Univ, Dept Psychol, Stanford, CA 94305 USA.
   [Dozier, Mary; Peloso, Elizabeth] Univ Delaware, Dept Psychol, Delaware, OH USA.
   [Maheu, Francoise S.] Univ Montreal, Dept Psychiat, Montreal, PQ H3C 3J7, Canada.
   [Maheu, Francoise S.] CHU Ste Justine, Res Ctr, Ste Justine, Canada.
RP Mueller, SC (reprint author), Henri Dunantlaan 2, B-9000 Ghent, Belgium.
EM Sven.Mueller@UGent.be
FU Intramural NIH HHS [Z99 MH999999]; NIMH NIH HHS [R01 MH074374, R01
   MH052135, R01 MH084135]; PHS HHS [NIMG 84135, NIMG 52135, NIMG 74374]
NR 46
TC 12
Z9 12
U1 5
U2 18
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0145-2134
J9 CHILD ABUSE NEGLECT
JI Child Abuse Negl.
PD MAR
PY 2012
VL 36
IS 3
BP 217
EP 225
DI 10.1016/j.chiabu.2011.10.010
PG 9
WC Family Studies; Psychology, Social; Social Work
SC Family Studies; Psychology; Social Work
GA 926IB
UT WOS:000302823400003
PM 22425696
ER

PT J
AU Judd, LL
AF Judd, Lewis L.
TI DIMENSIONAL PARADIGM OF THE LONG-TERM COURSE OF UNIPOLAR MAJOR
   DEPRESSIVE DISORDER
SO DEPRESSION AND ANXIETY
LA English
DT Article
ID BRANCH COLLABORATIVE PROGRAM; WEEKLY SYMPTOMATIC STATUS; BIPOLAR-II
   DISORDERS; PSYCHOSOCIAL DISABILITY; NATURAL-HISTORY; FOLLOW-UP;
   RECOVERY; PSYCHOBIOLOGY
C1 [Judd, Lewis L.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
   [Judd, Lewis L.] NIMH, Bethesda, MD USA.
RP Judd, LL (reprint author), Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM ljudd@ucsd.edu
NR 17
TC 5
Z9 5
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1091-4269
J9 DEPRESS ANXIETY
JI Depress. Anxiety
PD MAR
PY 2012
VL 29
IS 3
BP 167
EP 171
DI 10.1002/da.21934
PG 5
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 927JY
UT WOS:000302904700001
PM 22511337
ER

PT J
AU Timpano, KR
   Rubenstein, LM
   Murphy, DL
AF Timpano, Kiara R.
   Rubenstein, Liza M.
   Murphy, Dennis L.
TI Phenomenological features and clinical impact of affective disorders in
   OCD: a focus on the bipolar disorder and ocd connection
SO DEPRESSION AND ANXIETY
LA English
DT Article
DE obsessive-compulsive disorder; comorbidity; bipolar disorder;
   depression; anxiety disorders
ID OBSESSIVE-COMPULSIVE DISORDER; NATIONAL-COMORBIDITY-SURVEY;
   POSTTRAUMATIC-STRESS-DISORDER; DSM-III-R; MAJOR DEPRESSION; 12-MONTH
   PREVALENCE; SURVEY REPLICATION; GLOBAL ASSESSMENT; SCALE; RELIABILITY
AB Background: Given the general population prevalence rates of obsessive compulsive disorder (OCD) and the affective disorders, one would expect the co-occurrence of these syndromes to be rare. Yet findings by our group and others have revealed extremely high rates of comorbidity in OCD with both depressive disorders (DD; 50%) and bipolar disorder (BPD; 10%). The current investigation sought to further clarify the role affective disorder comorbidity-particularly that with BPD-may play in the clinical expression of OCD. Method: A total of 605 individuals with OCD were evaluated with the Structured Clinical Interview for DSM-IV. The sample included three groups: BPD (bipolar I or II; N=79, 13.1%), DD (major depression or dysthymia; N=388, 64.1%), and NAD (no affective disorder comorbidity; N=138, 22.8%). Group-wise comparisons were conducted on comorbidity patterns, impairment measures, and clinical features of OCD. Results: Analyses revealed a graded severity pattern, with the BPD group as the most severe, followed by the DD group, and finally the NAD group. Severity was reflected by the total number of Axis I disorders (P<.01), the number of psychiatric hospitalizations (P<.001), impairment measures (Ps<.05), and OCD symptoms (P<.01). It is worth noting that the impairment and OCD symptom severity findings were not attributable to the higher level of nonmood disorder comorbidities in the BPD and DD groups. Conclusion: Those individuals with comorbid affective disorders, particularly BPD, represent a clinically severe group compared to those without such comorbidity. Clarifying the phenomenological features of OCD-affective disorder comorbidity has important etiological and treatment implications. Depression and Anxiety 29:226-233, 2012. (C) 2011 Wiley Periodicals Inc.
C1 [Timpano, Kiara R.] Univ Miami, Dept Psychol, Coral Gables, FL 33146 USA.
   [Rubenstein, Liza M.; Murphy, Dennis L.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA.
RP Timpano, KR (reprint author), Univ Miami, Dept Psychol, 5665 Ponce de Leon Blvd, Coral Gables, FL 33146 USA.
EM kiaratimpano@gmail.com
OI Timpano, Kiara/0000-0002-0665-8722
FU NIMH, NIH
FX This research was supported by the Intramural Research Program of the
   NIMH, NIH. The authors thank F. J. McMahon for helpful discussions, as
   well as T. DeGuzman, B. L. Justement, and D. Kazuba for their
   contributions to this research.
NR 50
TC 11
Z9 12
U1 2
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1091-4269
J9 DEPRESS ANXIETY
JI Depress. Anxiety
PD MAR
PY 2012
VL 29
IS 3
BP 226
EP 233
DI 10.1002/da.20908
PG 8
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 927JY
UT WOS:000302904700009
PM 22109969
ER

PT J
AU Rouault, TA
AF Rouault, Tracey A.
TI Biogenesis of iron-sulfur clusters in mammalian cells: new insights and
   relevance to human disease
SO DISEASE MODELS & MECHANISMS
LA English
DT Editorial Material
ID FE-S PROTEINS; CONGENITAL SIDEROBLASTIC ANEMIA; FRIEDREICHS-ATAXIA;
   SCAFFOLD PROTEIN; COMPLEX-I; LACTIC-ACIDOSIS; CAUSES MYOPATHY; DOMAIN
   PROTEIN; YEAST FRATAXIN; HOMEOSTASIS
AB Iron-sulfur (Fe-S) clusters are ubiquitous cofactors composed of iron and inorganic sulfur. They are required for the function of proteins involved in a wide range of activities, including electron transport in respiratory chain complexes, regulatory sensing, photosynthesis and DNA repair. The proteins involved in the biogenesis of Fe-S clusters are evolutionarily conserved from bacteria to humans, and many insights into the process of Fe-S cluster biogenesis have come from studies of model organisms, including bacteria, fungi and plants. It is now clear that several rare and seemingly dissimilar human diseases are attributable to defects in the basic process of Fe-S cluster biogenesis. Although these diseases which include Friedreich's ataxia (FRDA), ISCU myopathy, a rare form of sideroblastic anemia, an encephalomyopathy caused by dysfunction of respiratory chain complex I and multiple mitochondrial dysfunctions syndrome - affect different tissues, a feature common to many of them is that mitochondrial iron overload develops as a secondary consequence of a defect in Fe-S cluster biogenesis. This Commentary outlines the basic steps of Fe-S cluster biogenesis as they have been defined in model organisms. In addition, it draws attention to refinements of the process that might be specific to the subcellular compartmentalization of Fe-S cluster biogenesis proteins in some eukaryotes, including mammals. Finally, it outlines several important unresolved questions in the field that, once addressed, should offer important clues into how mitochondrial iron homeostasis is regulated, and how dysfunction in Fe-S cluster biogenesis can contribute to disease.
C1 NICHHD, Bethesda, MD 20892 USA.
RP Rouault, TA (reprint author), NICHHD, Bethesda, MD 20892 USA.
EM Rouault@mail.nih.gov
NR 83
TC 119
Z9 122
U1 4
U2 27
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
   CAMBS, ENGLAND
SN 1754-8403
J9 DIS MODEL MECH
JI Dis. Model. Mech.
PD MAR
PY 2012
VL 5
IS 2
BP 155
EP 164
DI 10.1242/dmm.009019
PG 10
WC Cell Biology; Pathology
SC Cell Biology; Pathology
GA 927IA
UT WOS:000302899700002
PM 22382365
ER

PT J
AU Trunova, S
   Giniger, E
AF Trunova, Svetlana
   Giniger, Edward
TI Absence of the Cdk5 activator p35 causes adult-onset neurodegeneration
   in the central brain of Drosophila
SO DISEASE MODELS & MECHANISMS
LA English
DT Article
ID CYCLIN-DEPENDENT KINASE-5; ALZHEIMERS-DISEASE; NERVOUS-SYSTEM; IN-VIVO;
   AUTOPHAGY; PHOSPHORYLATION; DISRUPTION; NEURONS; DEATH; MELANOGASTER
AB Altered function of Cdk5 kinase is associated with many forms of neurodegenerative disease in humans. We show here that inactivating the Drosophila Cdk5 ortholog, by mutation of its activating subunit, p35, causes adult-onset neurodegeneration in the fly. In the mutants, a vacuolar neuropathology is observed in a specific structure of the central brain, the 'mushroom body', which is the seat of olfactory learning and memory. Analysis of cellular phenotypes in the mutant brains reveals some phenotypes that resemble natural aging in control flies, including an increase in apoptotic and necrotic cell death, axonal fragmentation, and accumulation of autophagosomes packed with crystalline-like depositions. Other phenotypes are unique to the mutants, notably age-dependent swellings of the proximal axon of mushroom body neurons. Many of these phenotypes are also characteristic of mammalian neurodegenerative disease, suggesting a close relationship between the mechanisms of Cdk5-associated neurodegeneration in fly and human. Together, these results identify the cellular processes that are unleashed in the absence of Cdk5 to initiate the neurodegenerative program, and they provide a model that can be used to determine what part each process plays in the progression to ultimate degeneration.
C1 [Trunova, Svetlana; Giniger, Edward] Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA.
   [Trunova, Svetlana; Giniger, Edward] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Giniger, E (reprint author), Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA.
EM ginigere@ninds.nih.gov
RI Giniger, Edward/C-1764-2015
OI Giniger, Edward/0000-0002-8340-6158
FU NINDS, National Institutes of Health (NIH) [Z01 NS003106]
FX This work was supported by the Basic Neuroscience Program of the
   Intramural Research Program, NINDS, National Institutes of Health (NIH)
   [Z01 NS003106].
NR 54
TC 10
Z9 12
U1 0
U2 3
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
   CAMBS, ENGLAND
SN 1754-8403
J9 DIS MODEL MECH
JI Dis. Model. Mech.
PD MAR
PY 2012
VL 5
IS 2
BP 210
EP 219
DI 10.1242/dmm.008847
PG 10
WC Cell Biology; Pathology
SC Cell Biology; Pathology
GA 927IA
UT WOS:000302899700007
PM 22228754
ER

PT J
AU Campa, D
   Kaaks, R
   Le Marchand, L
   Haiman, CA
   Travis, R
   Ziegler, RG
   Hunter, DJ
   Lindstrom, S
   Canzian, F
AF Campa, D.
   Kaaks, R.
   Le Marchand, L.
   Haiman, C. A.
   Travis, R.
   Ziegler, R. G.
   Hunter, D. J.
   Lindstroem, S.
   Canzian, F.
TI An Investigation of Interactions Between Genetic Variants and
   Established Risk Factors for Breast Cancer in the NCI Breast and
   Prostate Cancer Cohort Consortium (BPC3)
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 8th European Breast Cancer Conference (EBCC)
CY MAR 21-24, 2012
CL Vienna, AUSTRIA
SP European Canc Org (ECCO)
C1 [Campa, D.; Kaaks, R.; Canzian, F.] German Canc Res Ctr, D-6900 Heidelberg, Germany.
   [Le Marchand, L.] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA.
   [Haiman, C. A.] Univ So Calif, Los Angeles, CA USA.
   [Travis, R.] Univ Oxford, Canc Epidemiol Unit, Oxford, England.
   [Ziegler, R. G.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Hunter, D. J.; Lindstroem, S.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
RI Campa, Daniele/K-1617-2016
OI Campa, Daniele/0000-0003-3220-9944
NR 0
TC 0
Z9 0
U1 0
U2 5
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD MAR
PY 2012
VL 48
SU 1
BP S167
EP S168
PG 2
WC Oncology
SC Oncology
GA 926AV
UT WOS:000302804600424
ER

PT J
AU Rowland, J
AF Rowland, J.
TI Cancer Survivorship: NCI research and insights into this new and growing
   area
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 8th European Breast Cancer Conference (EBCC)
CY MAR 21-24, 2012
CL Vienna, AUSTRIA
SP European Canc Org (ECCO)
C1 [Rowland, J.] NCI, Off Canc Survivorship, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD MAR
PY 2012
VL 48
SU 1
BP S47
EP S47
PG 1
WC Oncology
SC Oncology
GA 926AV
UT WOS:000302804600037
ER

PT J
AU Peters, JA
   Kenen, R
   Hoskins, LM
   Glenn, GM
   Kratz, C
   Greene, MH
AF Peters, June A.
   Kenen, Regina
   Hoskins, Lindsey M.
   Glenn, Gladys M.
   Kratz, Christian
   Greene, Mark H.
TI Close ties: an exploratory Colored Eco-Genetic Relationship Map (CEGRM)
   study of social connections of men in Familial Testicular Cancer (FTC)
   families
SO HEREDITARY CANCER IN CLINICAL PRACTICE
LA English
DT Article
ID GERM-CELL TUMORS; LONG-TERM SURVIVORS; QUALITY-OF-LIFE; HEREDITARY
   BREAST; BREAST/OVARIAN CANCER; MARITAL RELATIONSHIPS; HEALTH
   COMMUNICATION; RISK-FACTOR; YOUNG MEN; MICROLITHIASIS
AB Background: Testicular cancer, while rare compared with other adult solid tumors, is the most common cancer in young men in northern Europe and North America. Risk factors include white race, positive family history, contralateral testicular cancer, cryptorchidism, infertility and testicular microlithiasis. As the genetic causes of familial clusters (Familial Testicular Cancer of FTC) are being sought, it is also important to understand the psycho-social experiences of members of FTC families.
   Methods: This is a cross-sectional examination via the Colored Eco-Genetic Relationship Map (CEGRM) of social connections reported by 49 men in FTC families participating in NCI research study 02-C-178.
   Results: The CEGRM was acceptable and feasible for use with men in FTC families, and valuable in understanding their social connections. These men have largely adjusted to the TC history in themselves and/or their relatives. They have considerable social and emotional support from family and friends, although there is wide variability in sources and types.
   Conclusions: The CEGRM focuses on men's social connections and close emotional bonds in FTC families. This action-oriented process of placing colored symbols on significant relationships uncovered previously under-appreciated emotions accompanying men's social exchanges. Most men in FTC families succeed in re-establishing a sense of normalcy in their lives and social connections, in the aftermath of a testicular cancer diagnosis.
C1 [Peters, June A.; Hoskins, Lindsey M.; Glenn, Gladys M.; Kratz, Christian; Greene, Mark H.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,US Dept HHS, Rockville, MD 20852 USA.
   [Kenen, Regina] Coll New Jersey, Dept Sociol & Anthropol, Ewing, NJ USA.
RP Peters, JA (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,US Dept HHS, 6120 Execut Blvd, Rockville, MD 20852 USA.
EM petersju@mail.nih.gov
FU Division of Cancer Epidemiology and Genetics of the National Cancer
   Institute within U.S. National Institutes of Health; Westat, Inc.,
   Rockville, MD, USA [NO2-CP-11019-50, N02-CP-65504]
FX This work was supported by the Division of Cancer Epidemiology and
   Genetics of the National Cancer Institute within the Intramural Research
   Programs of the U.S. National Institutes of Health, and by support
   services contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Inc.,
   Rockville, MD, USA.
NR 72
TC 2
Z9 2
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1731-2302
J9 HERED CANCER CLIN PR
JI Hered. Cancer Clin. Pract.
PD MAR 1
PY 2012
VL 10
AR 2
DI 10.1186/1897-4287-10-2
PG 14
WC Oncology
SC Oncology
GA 926WO
UT WOS:000302862800001
PM 22381132
ER

PT J
AU Sun, JX
   Horst, OV
   Bumgarner, R
   Lakely, B
   Somerman, MJ
   Zhang, H
AF Sun, Jian-Xun
   Horst, Orapin V.
   Bumgarner, Roger
   Lakely, Bryce
   Somerman, Martha J.
   Zhang, Hai
TI Laser capture microdissection enables cellular and molecular studies of
   tooth root development
SO INTERNATIONAL JOURNAL OF ORAL SCIENCE
LA English
DT Article
DE gene; laser capture microdissection; microarray; PCR; root
ID EPITHELIAL-MESENCHYMAL INTERACTIONS; BONE MORPHOGENETIC PROTEINS; RICH
   AMELOGENIN PEPTIDE; RAT DENTAL FOLLICLE; STEM-CELLS; MACULAR
   DEGENERATION; GENE-EXPRESSION; FIBULIN-2 EXPRESSION; IN-VITRO; RNA
AB Epithelial-mesenchymal interactions (EMIs) are critical for tooth development. Molecular mechanisms mediating these interactions in root formation is not well understood. Laser capture microdissection (LCM) and subsequent microarray analyses enable large scale in situ molecular and cellular studies of root formation but to date have been hindered by technical challenges of gaining intact histological sections of non-decalcified mineralized teeth or jaws with well-preserved RNA. Here, we describe a new method to overcome this obstacle that permits LCM of dental epithelia, adjacent mesenchyme, odontoblasts and cementoblasts from mouse incisors and molars during root development. Using this method, we obtained RNA samples of high quality and successfully performed microarray analyses. Robust differences in gene expression, as well as genes not previously associated with root formation, were identified. Comparison of gene expression data from microarray with real-time reverse transcriptase polymerase chain reaction (RT-PCR) supported our findings. These genes include known markers of dental epithelia, mesenchyme, cementoblasts and odontoblasts, as well as novel genes such as those in the fibulin family. In conclusion, our new approach in tissue preparation enables LCM collection of intact cells with well-preserved RNA allowing subsequent gene expression analyses using microarray and RT-PCR to define key regulators of tooth root development. International Journal of Oral Science (2012) 4, 7-13; doi:10.1038/ijos.2012.15; published online 16 March 2012
C1 [Sun, Jian-Xun] Sichuan Univ, State Key Lab Oral Dis, Chengdu 610064, Peoples R China.
   [Sun, Jian-Xun] Univ Washington, Dept Periodontol, Seattle, WA 98195 USA.
   [Horst, Orapin V.] Univ Calif San Francisco, Dept Prevent & Restorat Dent Sci, Div Endodont, San Francisco, CA 94143 USA.
   [Bumgarner, Roger] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA.
   [Lakely, Bryce] Univ Washington, Dept Urol, Seattle, WA 98195 USA.
   [Somerman, Martha J.] NIAMSD, NIH, Bethesda, MD 20892 USA.
   [Zhang, Hai] Univ Washington, Dept Restorat Dent, Seattle, WA 98195 USA.
RP Zhang, H (reprint author), 1959 NE Pacific St,Box 357456, Seattle, WA 98195 USA.
EM haizhang@u.washington.edu
RI Bumgarner, Roger/K-3531-2015
OI Bumgarner, Roger/0000-0002-8168-6985
FU NIH [DE15109]; State Key Laboratory of Oral Diseases in Chengdu, China
FX The authors would like to thank Dr Robert L Vessella and Dr Colm
   Morrissey in the Department of Urology, University of Washington for
   their technical support of LCM; Dr Theo Bammler, Dr Michael Coon and Dr
   Dick Beyer in the Department of Environmental and Occupational Health
   Sciences, University of Washington for their technical assistance in
   microarray analyses; Dr Brian Foster for his critical comments. This
   work is supported by NIH grant no. DE15109 to Dr Martha Somerman and a
   grant from the State Key Laboratory of Oral Diseases in Chengdu, China
   to Dr Hai Zhang.
NR 59
TC 7
Z9 7
U1 0
U2 13
PU SICHUAN UNIV
PI CHENGDU
PA SICHUAN UNIV, CHENGDU, SICHUAN, 610064 00000, PEOPLES R CHINA
SN 1674-2818
J9 INT J ORAL SCI
JI Int. J. Oral Sci.
PD MAR
PY 2012
VL 4
IS 1
BP 7
EP 13
DI 10.1038/ijos.2012.15
PG 7
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 927RI
UT WOS:000302927400002
PM 22422086
ER

PT J
AU Hong, SH
   Ren, L
   Mendoza, A
   Eleswarapu, A
   Khanna, C
AF Hong, Sung-Hyeok
   Ren, Ling
   Mendoza, Arnulfo
   Eleswarapu, Ananth
   Khanna, Chand
TI Apoptosis Resistance and PKC Signaling: Distinguishing Features of High
   and Low Metastatic Cells
SO NEOPLASIA
LA English
DT Article
ID BREAST-CANCER METASTASIS; TUMOR-CELLS; IN-VIVO; OSTEOSARCOMA PATIENTS;
   AKT ACTIVATION; EWINGS-SARCOMA; MAMMARY-TUMOR; LINKER EZRIN; MOUSE
   MODEL; REAL-TIME
AB The complexity of the process of metastasis is widely recognized. We report herein on a recurrent feature of high compared to low metastatic cells that is linked to their ability to survive early after their arrival at secondary sites. Using novel fluorescent-based imaging strategies that assess tumor cell interaction with the lung microenvironment, we have determined that most high and low metastatic cells can be distinguished within 6 hours of their arrival in the lung and further that this difference is defined by the ability of highmetastatic cells to resist apoptosis at the secondary site. Despite the complexity of the metastatic cascade, the performance of cells during this critical window is highly defining of their metastatic proclivity. To explore mechanisms, we next evaluated biochemical pathways that may be linked to this survival phenotype in highly metastatic cells. Interestingly, we found no association between the Akt survival pathway and this metastatic phenotype. Of all pathways examined, only protein kinase C (PKC) activation was significantly linked to survival of highly metastatic cells. These data provide a conceptual understanding of a defining difference between high and low metastatic cells. The connection to PKC activation may provide a biologic rationale for the use of PKC inhibition in the prevention of metastatic progression.
C1 [Hong, Sung-Hyeok; Ren, Ling; Mendoza, Arnulfo; Eleswarapu, Ananth; Khanna, Chand] NCI, Tumor & Metastasis Biol Sect, Pediat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
   [Eleswarapu, Ananth] Howard Hughes Med Inst, NIH, Res Scholars Program, Bethesda, MD 20817 USA.
RP Khanna, C (reprint author), NCI, Tumor & Metastasis Biol Sect, Pediat Oncol Branch, Ctr Canc Res,NIH, 37 Convent Dr,Bldg 37,Room 2144, Bethesda, MD 20892 USA.
EM khannac@mail.nih.gov
FU National Institutes of Health
FX This research was supported by the Intramural Research Program of the
   National Institutes of Health. The authors declare no conflict of
   interest.
NR 48
TC 7
Z9 8
U1 0
U2 4
PU NEOPLASIA PRESS
PI ANN ARBOR
PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648
   USA
SN 1522-8002
J9 NEOPLASIA
JI Neoplasia
PD MAR
PY 2012
VL 14
IS 3
BP 249
EP +
DI 10.1593/neo.111498
PG 13
WC Oncology
SC Oncology
GA 922HW
UT WOS:000302539000008
PM 22496624
ER

PT J
AU Busser, BW
   Taher, L
   Kim, Y
   Tansey, T
   Bloom, MJ
   Ovcharenko, I
   Michelson, AM
AF Busser, Brian W.
   Taher, Leila
   Kim, Yongsok
   Tansey, Terese
   Bloom, Molly J.
   Ovcharenko, Ivan
   Michelson, Alan M.
TI A Machine Learning Approach for Identifying Novel Cell Type-Specific
   Transcriptional Regulators of Myogenesis
SO PLOS GENETICS
LA English
DT Article
ID COMMON ORGANIZATIONAL FEATURES; DROSOPHILA EMBRYONIC MESODERM;
   GENOME-WIDE DISCOVERY; GENE-EXPRESSION; MUSCLE PROGENITORS; DNA-BINDING;
   HEART ENHANCERS; HOMEOBOX GENE; HOX PROTEINS; TARGET GENES
AB Transcriptional enhancers integrate the contributions of multiple classes of transcription factors (TFs) to orchestrate the myriad spatio-temporal gene expression programs that occur during development. A molecular understanding of enhancers with similar activities requires the identification of both their unique and their shared sequence features. To address this problem, we combined phylogenetic profiling with a DNA-based enhancer sequence classifier that analyzes the TF binding sites (TFBSs) governing the transcription of a co-expressed gene set. We first assembled a small number of enhancers that are active in Drosophila melanogaster muscle founder cells (FCs) and other mesodermal cell types. Using phylogenetic profiling, we increased the number of enhancers by incorporating orthologous but divergent sequences from other Drosophila species. Functional assays revealed that the diverged enhancer orthologs were active in largely similar patterns as their D. melanogaster counterparts, although there was extensive evolutionary shuffling of known TFBSs. We then built and trained a classifier using this enhancer set and identified additional related enhancers based on the presence or absence of known and putative TFBSs. Predicted FC enhancers were over-represented in proximity to known FC genes; and many of the TFBSs learned by the classifier were found to be critical for enhancer activity, including POU homeodomain, Myb, Ets, Forkhead, and T-box motifs. Empirical testing also revealed that the T-box TF encoded by org-1 is a previously uncharacterized regulator of muscle cell identity. Finally, we found extensive diversity in the composition of TFBSs within known FC enhancers, suggesting that motif combinatorics plays an essential role in the cellular specificity exhibited by such enhancers. In summary, machine learning combined with evolutionary sequence analysis is useful for recognizing novel TFBSs and for facilitating the identification of cognate TFs that coordinate cell type-specific developmental gene expression patterns.
C1 [Busser, Brian W.; Kim, Yongsok; Tansey, Terese; Bloom, Molly J.; Michelson, Alan M.] NHLBI, Lab Dev Syst Biol, NIH, Bethesda, MD 20892 USA.
   [Taher, Leila; Ovcharenko, Ivan] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
RP Busser, BW (reprint author), NHLBI, Lab Dev Syst Biol, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM ovcharen@nih.gov; michelsonam@nhlbi.nih.gov
FU NHLBI Division of Intramural Research; NIH, National Library of Medicine
FX This work was funded by the NHLBI Division of Intramural Research (AMM)
   and the Intramural Research Program of the NIH, National Library of
   Medicine (IO). The funders had no role in study design, data collection
   and analysis, decision to publish, or preparation of the manuscript.
NR 124
TC 23
Z9 23
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD MAR
PY 2012
VL 8
IS 3
AR e1002531
DI 10.1371/journal.pgen.1002531
PG 21
WC Genetics & Heredity
SC Genetics & Heredity
GA 918MV
UT WOS:000302254800012
PM 22412381
ER

PT J
AU Galanter, JM
   Fernandez-Lopez, JC
   Gignoux, CR
   Barnholtz-Sloan, J
   Fernandez-Rozadilla, C
   Via, M
   Hidalgo-Miranda, A
   Contreras, AV
   Figueroa, LU
   Raska, P
   Jimenez-Sanchez, G
   Zolezzi, IS
   Torres, M
   Ponte, CR
   Ruiz, Y
   Salas, A
   Nguyen, E
   Eng, C
   Borjas, L
   Zabala, W
   Barreto, G
   Gonzalez, FR
   Ibarra, A
   Taboada, P
   Porras, L
   Moreno, F
   Bigham, A
   Gutierrez, G
   Brutsaert, T
   Leon-Velarde, F
   Moore, LG
   Vargas, E
   Cruz, M
   Escobedo, J
   Rodriguez-Santana, J
   Rodriguez-Cintron, W
   Chapela, R
   Ford, JG
   Bustamante, C
   Seminara, D
   Shriver, M
   Ziv, E
   Burchard, EG
   Haile, R
   Parra, E
   Carracedo, A
AF Galanter, Joshua Mark
   Carlos Fernandez-Lopez, Juan
   Gignoux, Christopher R.
   Barnholtz-Sloan, Jill
   Fernandez-Rozadilla, Ceres
   Via, Marc
   Hidalgo-Miranda, Alfredo
   Contreras, Alejandra V.
   Uribe Figueroa, Laura
   Raska, Paola
   Jimenez-Sanchez, Gerardo
   Silva Zolezzi, Irma
   Torres, Maria
   Ruiz Ponte, Clara
   Ruiz, Yarimar
   Salas, Antonio
   Nguyen, Elizabeth
   Eng, Celeste
   Borjas, Lisbeth
   Zabala, William
   Barreto, Guillermo
   Rondon Gonzalez, Fernando
   Ibarra, Adriana
   Taboada, Patricia
   Porras, Liliana
   Moreno, Fabian
   Bigham, Abigail
   Gutierrez, Gerardo
   Brutsaert, Tom
   Leon-Velarde, Fabiola
   Moore, Lorna G.
   Vargas, Enrique
   Cruz, Miguel
   Escobedo, Jorge
   Rodriguez-Santana, Jose
   Rodriguez-Cintron, William
   Chapela, Rocio
   Ford, Jean G.
   Bustamante, Carlos
   Seminara, Daniela
   Shriver, Mark
   Ziv, Elad
   Burchard, Esteban Gonzalez
   Haile, Robert
   Parra, Esteban
   Carracedo, Angel
CA LACE Consortium
TI Development of a Panel of Genome-Wide Ancestry Informative Markers to
   Study Admixture Throughout the Americas
SO PLOS GENETICS
LA English
DT Article
ID NUCLEOTIDE-POLYMORPHISM PANEL; POPULATION-STRUCTURE; AFRICAN-AMERICANS;
   HISPANIC/LATINO POPULATIONS; GENETIC RELATEDNESS; STARR COUNTY;
   MEXICO-CITY; ASSOCIATION; INFERENCE; LINKAGE
AB Most individuals throughout the Americas are admixed descendants of Native American, European, and African ancestors. Complex historical factors have resulted in varying proportions of ancestral contributions between individuals within and among ethnic groups. We developed a panel of 446 ancestry informative markers (AIMs) optimized to estimate ancestral proportions in individuals and populations throughout Latin America. We used genome-wide data from 953 individuals from diverse African, European, and Native American populations to select AIMs optimized for each of the three main continental populations that form the basis of modern Latin American populations. We selected markers on the basis of locus-specific branch length to be informative, well distributed throughout the genome, capable of being genotyped on widely available commercial platforms, and applicable throughout the Americas by minimizing within-continent heterogeneity. We then validated the panel in samples from four admixed populations by comparing ancestry estimates based on the AIMs panel to estimates based on genome-wide association study (GWAS) data. The panel provided balanced discriminatory power among the three ancestral populations and accurate estimates of individual ancestry proportions (R-2 > 0.9 for ancestral components with significant between-subject variance). Finally, we genotyped samples from 18 populations from Latin America using the AIMs panel and estimated variability in ancestry within and between these populations. This panel and its reference genotype information will be useful resources to explore population history of admixture in Latin America and to correct for the potential effects of population stratification in admixed samples in the region.
C1 [Galanter, Joshua Mark; Gignoux, Christopher R.; Nguyen, Elizabeth; Eng, Celeste; Ziv, Elad; Burchard, Esteban Gonzalez] Univ Calif San Francisco, San Francisco, CA 94143 USA.
   [Carlos Fernandez-Lopez, Juan; Hidalgo-Miranda, Alfredo; Contreras, Alejandra V.; Uribe Figueroa, Laura; Jimenez-Sanchez, Gerardo; Silva Zolezzi, Irma] Inst Nacl Med Genom, Mexico City, DF, Mexico.
   [Barnholtz-Sloan, Jill; Raska, Paola] Case Western Reserve Univ, Cleveland, OH 44106 USA.
   [Fernandez-Rozadilla, Ceres; Torres, Maria; Ruiz Ponte, Clara; Ruiz, Yarimar; Salas, Antonio; Zabala, William; Taboada, Patricia; Porras, Liliana; Carracedo, Angel] Univ Santiago de Compostela, CIBERER, Fdn Publ Galega Med Xen SERGAS, Santiago De Compostela, Spain.
   [Via, Marc] Univ Barcelona, Barcelona, Spain.
   [Borjas, Lisbeth; Zabala, William] Univ Zulia, Maracaibo 4011, Venezuela.
   [Barreto, Guillermo] Univ Valle, Santiago De Cali, Colombia.
   [Rondon Gonzalez, Fernando] Univ Ind Santander, Bucaramanga, Colombia.
   [Ibarra, Adriana] Univ Antioquia, Medellin, Colombia.
   [Taboada, Patricia] Inst Invest Forenses, Sucre, Bolivia.
   [Porras, Liliana] Univ Tecnol Pereira, Pereira, Colombia.
   [Moreno, Fabian] Serv Med Legal Chile, Unidad Genet Forense, Santiago, Chile.
   [Bigham, Abigail] Univ Michigan, Ann Arbor, MI 48109 USA.
   [Gutierrez, Gerardo] Univ Colorado, Boulder, CO 80309 USA.
   [Brutsaert, Tom] Syracuse Univ, Syracuse, NY USA.
   [Leon-Velarde, Fabiola] Univ Peruana Cayetano Heredia, Lima, Peru.
   [Moore, Lorna G.] Wake Forest Univ, Winston Salem, NC 27109 USA.
   [Vargas, Enrique] Univ Mayor de San Andres, La Paz, Bolivia.
   [Cruz, Miguel] Mexican Social Secur Inst IMSS, Ctr Med Nacl Siglo 21, Mexico City, DF, Mexico.
   [Escobedo, Jorge] Hosp Gen Reg 1, IMSS, Mexico City, DF, Mexico.
   [Rodriguez-Santana, Jose] Ctr Neumol Pediat, San Juan, PR USA.
   [Rodriguez-Cintron, William] VA Caribbean Hlth Syst, San Juan, PR USA.
   [Chapela, Rocio] INER, Mexico City, DF, Mexico.
   [Ford, Jean G.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
   [Bustamante, Carlos] Stanford Univ, Stanford, CA 94305 USA.
   [Seminara, Daniela] NCI, Bethesda, MD 20892 USA.
   [Shriver, Mark] Penn State Univ, University Pk, PA 16802 USA.
   [Haile, Robert] Univ So Calif, Los Angeles, CA USA.
   [Parra, Esteban] Univ Toronto, Mississauga, ON L5L 1C6, Canada.
RP Galanter, JM (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA.
EM joshua.galanter@ucsf.edu
RI Hidalgo-Miranda, Alfredo/B-2123-2010; Ziv, Elad/L-5396-2014; Via,
   Marc/L-6511-2014; Fernandez, Juan Carlos/C-4976-2013; Salas,
   Antonio/E-3977-2012; Ruiz-Ponte, Clara/I-3849-2015; Contreras, Alejandra
   Virginia/E-7815-2013
OI Nguyen, Elizabeth/0000-0002-8070-6382; parra, esteban
   J/0000-0002-2057-8577; Hidalgo-Miranda, Alfredo/0000-0003-2315-3977;
   Carracedo, Angel/0000-0003-1085-8986; Via, Marc/0000-0002-9966-9921;
   Fernandez, Juan Carlos/0000-0003-3680-4193; Salas,
   Antonio/0000-0002-2336-702X; Ruiz-Ponte, Clara/0000-0002-2200-0162;
   Fernandez-Rozadilla, Ceres/0000-0001-7330-4804; Torres,
   Maria/0000-0002-2658-0133; Contreras, Alejandra
   Virginia/0000-0003-3653-5958
FU National Cancer Institute; National Cancer Institute, National
   Institutes of Health [HHSN261201000641P]; NIH [R01HL078885, K23HL004464,
   5R01HL088133, R01HL079647, T32GM007546, 2KL2RR024130, T32GM007175];
   American Asthma Foundation; Sandler Foundation; Canadian Institutes of
   Health Research; Banting and Best Diabetes Centre; Canada Foundation for
   Innovation; Ontario Innovation Trust; CONACYT [SALUD-2005-C02-14412,
   2007-C01-71068]; Proyectos Estrategicos; Apoyo Financiero Fundacion
   IMSS; Fundacion Gonzalo Rio Arronte I, A.P. Mexico; FIS [PS09/02368];
   Ralph Hewitt Fellowship
FX This work was made possible by the Latin American Cancer Epidemiology
   (LACE) Consortium, which has been supported with travel/meeting grants
   from the National Cancer Institute and by Contract #HHSN261201000641P
   from the National Cancer Institute, National Institutes of Health. The
   GALA study was funded by the NIH (R01HL078885, K23HL004464,
   5R01HL088133), the American Asthma Foundation, and the Sandler
   Foundation. The Mexico City type 2 diabetes study was funded in Canada
   by the Canadian Institutes of Health Research, the Banting and Best
   Diabetes Centre, the Canada Foundation for Innovation, and The Ontario
   Innovation Trust, and in Mexico by the following grants: CONACYT
   SALUD-2005-C02-14412 and 2007-C01-71068, Proyectos Estrategicos, Apoyo
   Financiero Fundacion IMSS, and Fundacion Gonzalo Rio Arronte I, A.P.
   Mexico. Samples in Latin America were collected and typed with funding
   support from FIS PS09/02368 (FEDER funding). Samples in Bolivia were
   collected with funding support from the National Institutes of Health
   (R01HL079647). JMG received support from the National Institutes of
   Health (T32GM007546, 2KL2RR024130) and the Ralph Hewitt Fellowship. EP
   is the recipient of a CIHR New Investigator Award. CRG was supported in
   part by NIH Training Grant T32GM007175. The funders had no role in study
   design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
NR 61
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PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD MAR
PY 2012
VL 8
IS 3
AR e1002554
DI 10.1371/journal.pgen.1002554
PG 16
WC Genetics & Heredity
SC Genetics & Heredity
GA 918MV
UT WOS:000302254800030
PM 22412386
ER

PT J
AU Hill, NS
   Kadoya, R
   Chattoraj, DK
   Levin, PA
AF Hill, Norbert S.
   Kadoya, Ryosuke
   Chattoraj, Dhruba K.
   Levin, Petra Anne
TI Cell Size and the Initiation of DNA Replication in Bacteria
SO PLOS GENETICS
LA English
DT Article
ID ESCHERICHIA-COLI K-12; MEDIAL FTSZ RING; BACILLUS-SUBTILIS;
   CHROMOSOME-REPLICATION; DIVISION CYCLE; GROWTH-RATE;
   SALMONELLA-TYPHIMURIUM; PROTEIN DETERMINES; GENE; MUTANT
AB In eukaryotes, DNA replication is coupled to the cell cycle through the actions of cyclin-dependent kinases and associated factors. In bacteria, the prevailing view, based primarily from work in Escherichia coli, is that growth-dependent accumulation of the highly conserved initiator, DnaA, triggers initiation. However, the timing of initiation is unchanged in Bacillus subtilis mutants that are,30% smaller than wild-type cells, indicating that achievement of a particular cell size is not obligatory for initiation. Prompted by this finding, we re-examined the link between cell size and initiation in both E. coli and B. subtilis. Although changes in DNA replication have been shown to alter both E. coli and B. subtilis cell size, the converse ( the effect of cell size on DNA replication) has not been explored. Here, we report that the mechanisms responsible for coordinating DNA replication with cell size vary between these two model organisms. In contrast to B. subtilis, small E. coli mutants delayed replication initiation until they achieved the size at which wild-type cells initiate. Modest increases in DnaA alleviated the delay, supporting the view that growth-dependent accumulation of DnaA is the trigger for replication initiation in E. coli. Significantly, although small E. coli and B. subtilis cells both maintained wild-type concentration of DnaA, only the E. coli mutants failed to initiate on time. Thus, rather than the concentration, the total amount of DnaA appears to be more important for initiation timing in E. coli. The difference in behavior of the two bacteria appears to lie in the mechanisms that control the activity of DnaA.
C1 [Hill, Norbert S.; Levin, Petra Anne] Washington Univ, Dept Biol, St Louis, MO 63130 USA.
   [Kadoya, Ryosuke; Chattoraj, Dhruba K.] NCI, Lab Biochem & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Hill, NS (reprint author), Washington Univ, Dept Biol, Campus Box 1137, St Louis, MO 63130 USA.
EM plevin@wustl.edu
FU Public Health Services from NIH [GM64671]; CCR, NCI
FX This work was supported by Public Health Services grant (GM64671) from
   the NIH to PAL and by Intramural Research Program, CCR, NCI, to RK and
   DKC. The funders had no role in study design, data collection and
   analysis, decision to publish, or preparation of the manuscript.
NR 70
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PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD MAR
PY 2012
VL 8
IS 3
AR e1002549
DI 10.1371/journal.pgen.1002549
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA 918MV
UT WOS:000302254800025
PM 22396664
ER

PT J
AU Lill, CM
   Roehr, JT
   McQueen, MB
   Kavvoura, FK
   Bagade, S
   Schjeide, BMM
   Schjeide, LM
   Meissner, E
   Zauft, U
   Allen, NC
   Liu, T
   Schilling, M
   Anderson, KJ
   Beecham, G
   Berg, D
   Biernacka, JM
   Brice, A
   DeStefano, AL
   Do, CB
   Eriksson, N
   Factor, SA
   Farrer, MJ
   Foroud, T
   Gasser, T
   Hamza, T
   Hardy, JA
   Heutink, P
   Hill-Burns, EM
   Klein, C
   Latourelle, JC
   Maraganore, DM
   Martin, ER
   Martinez, M
   Myers, RH
   Nalls, MA
   Pankratz, N
   Payami, H
   Satake, W
   Scott, WK
   Sharma, M
   Singleton, AB
   Stefansson, K
   Toda, T
   Tung, JY
   Vance, J
   Wood, NW
   Zabetian, CP
   Young, P
   Tanzi, RE
   Khoury, MJ
   Zipp, F
   Lehrach, H
   Ioannidis, JPA
   Bertram, L
AF Lill, Christina M.
   Roehr, Johannes T.
   McQueen, Matthew B.
   Kavvoura, Fotini K.
   Bagade, Sachin
   Schjeide, Brit-Maren M.
   Schjeide, Leif M.
   Meissner, Esther
   Zauft, Ute
   Allen, Nicole C.
   Liu, Tian
   Schilling, Marcel
   Anderson, Kari J.
   Beecham, Gary
   Berg, Daniela
   Biernacka, Joanna M.
   Brice, Alexis
   DeStefano, Anita L.
   Do, Chuong B.
   Eriksson, Nicholas
   Factor, Stewart A.
   Farrer, Matthew J.
   Foroud, Tatiana
   Gasser, Thomas
   Hamza, Taye
   Hardy, John A.
   Heutink, Peter
   Hill-Burns, Erin M.
   Klein, Christine
   Latourelle, Jeanne C.
   Maraganore, Demetrius M.
   Martin, Eden R.
   Martinez, Maria
   Myers, Richard H.
   Nalls, Michael A.
   Pankratz, Nathan
   Payami, Haydeh
   Satake, Wataru
   Scott, William K.
   Sharma, Manu
   Singleton, Andrew B.
   Stefansson, Kari
   Toda, Tatsushi
   Tung, Joyce Y.
   Vance, Jeffery
   Wood, Nick W.
   Zabetian, Cyrus P.
   Young, Peter
   Tanzi, Rudolph E.
   Khoury, Muin J.
   Zipp, Frauke
   Lehrach, Hans
   Ioannidis, John P. A.
   Bertram, Lars
CA Genetic Epidemiology Parkinson's
   IPDGC
   Parkinson's Dis GWAS Consortium
   WTCCC2
TI Comprehensive Research Synopsis and Systematic Meta-Analyses in
   Parkinson's Disease Genetics: The PDGene Database
SO PLOS GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; ALPHA-SYNUCLEIN; RISK-FACTORS; MUTATIONS;
   VARIANTS; SUSCEPTIBILITY; DATASETS; TRIALS; REGION; VPS35
C1 [Lill, Christina M.; Roehr, Johannes T.; Schjeide, Brit-Maren M.; Schjeide, Leif M.; Meissner, Esther; Zauft, Ute; Liu, Tian; Schilling, Marcel; Lehrach, Hans; Bertram, Lars] Max Planck Inst Mol Genet, Neuropsychiat Genet Grp, Dept Vertebrate Genom, D-14195 Berlin, Germany.
   [Lill, Christina M.; Bagade, Sachin; Allen, Nicole C.; Tanzi, Rudolph E.; Bertram, Lars] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA.
   [Lill, Christina M.; Zipp, Frauke] Johannes Gutenberg Univ Mainz, Dept Neurol, Med Ctr, Mainz, Germany.
   [Lill, Christina M.; Young, Peter] Univ Hosp, Dept Neurol, Munster, Germany.
   [Roehr, Johannes T.; Schilling, Marcel] Free Univ Berlin, Dept Math & Comp Sci, Berlin, Germany.
   [McQueen, Matthew B.] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA.
   [Kavvoura, Fotini K.; Ioannidis, John P. A.] Univ Ioannina, Sch Med, Clin & Mol Epidemiol Unit, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece.
   [Kavvoura, Fotini K.] Royal Berkshire Hosp, Ctr Diabet & Endocrinol, Reading RG1 5AN, Berks, England.
   [Kavvoura, Fotini K.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Churchill Hosp, Oxford, England.
   [Liu, Tian] Max Planck Inst Human Dev, Berlin, Germany.
   [Anderson, Kari J.; Biernacka, Joanna M.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
   [Beecham, Gary; Martin, Eden R.; Scott, William K.; Vance, Jeffery] Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Miami, FL 33136 USA.
   [Berg, Daniela; Gasser, Thomas; Sharma, Manu] Univ Tubingen, Dept Neurodegenerat Dis, Hertie Inst Clin Brain Res, Tubingen, Germany.
   [Berg, Daniela; Gasser, Thomas; Sharma, Manu] German Ctr Neurodegenerat Dis, DZNE, Tubingen, Germany.
   [Brice, Alexis] INSERM, UMR S975, Paris, France.
   [Brice, Alexis] Univ Paris 06, Ctr Rech, Inst Cerveau & Moelle Epiniere, UMR S975, Paris, France.
   [Brice, Alexis] CNRS, UMR 7225, Paris, France.
   [Brice, Alexis] Hop La Pitie Salpetriere, AP HP, Dept Genet & Cytogenet, Paris, France.
   [DeStefano, Anita L.; Latourelle, Jeanne C.; Myers, Richard H.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
   [DeStefano, Anita L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
   [Do, Chuong B.; Eriksson, Nicholas; Tung, Joyce Y.] 23andMe, Mountain View, CA USA.
   [Factor, Stewart A.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA.
   [Farrer, Matthew J.] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada.
   [Foroud, Tatiana; Pankratz, Nathan] Indiana Univ Sch Med, Indianapolis, IN USA.
   [Hamza, Taye; Hill-Burns, Erin M.; Payami, Haydeh] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA.
   [Hardy, John A.; Wood, Nick W.] UCL, Dept Mol Neurosci, UCL Inst Neurol, London, England.
   [Heutink, Peter] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Sect Med Genom, Amsterdam, Netherlands.
   [Klein, Christine] Univ Lubeck, Sect Clin & Mol Neurogenet, Dept Neurol, Lubeck, Germany.
   [Maraganore, Demetrius M.] NorthShore Univ Hlth Syst, Dept Neurol, Evanston, IL USA.
   [Martinez, Maria] Fac Med Toulouse, INSERM, UMR 1043, CPTP, F-31073 Toulouse, France.
   [Martinez, Maria] Univ Toulouse 3, F-31062 Toulouse, France.
   [Nalls, Michael A.; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
   [Satake, Wataru; Toda, Tatsushi] Kobe Univ, Grad Sch Med, Div Neurol Mol Brain Sci, Kobe, Hyogo 657, Japan.
   [Wood, Nick W.] UCL, UCL Genet Inst, London, England.
   [Stefansson, Kari] deCODE Genet, Reykjavik, Iceland.
   [Zabetian, Cyrus P.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA USA.
   [Zabetian, Cyrus P.] Univ Washington, Dept Neurol, Seattle, WA USA.
   [Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA.
   [Ioannidis, John P. A.] Fdn Res & Technol Hellas, Biomed Res Inst, Ioannina, Greece.
   [Ioannidis, John P. A.] Tufts Univ, Sch Med, Ctr Genet Epidemiol & Modeling, Boston, MA 02111 USA.
   [Ioannidis, John P. A.] Tufts Univ, Sch Med, Tufts Clin & Translat Sci Inst, Boston, MA 02111 USA.
   [Ioannidis, John P. A.] Stanford Univ, Dept Med, Stanford Prevent Res Ctr, Sch Med, Stanford, CA 94305 USA.
   [Ioannidis, John P. A.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
RP Lill, CM (reprint author), Max Planck Inst Mol Genet, Neuropsychiat Genet Grp, Dept Vertebrate Genom, Ihnestr 73, D-14195 Berlin, Germany.
EM lbertram@molgen.mpg.de
RI Hardy, John/C-2451-2009; Singleton, Andrew/C-3010-2009; Traynor,
   Bryan/G-5690-2010; Schilling, Marcel/O-3169-2013; Zipp,
   Frauke/C-9968-2015; Lill, Christina/J-9449-2015; Bertram,
   Lars/K-3889-2015; Martinez, Maria/B-3111-2013; Wood,
   Nicholas/C-2505-2009; 
OI Zabetian, Cyrus/0000-0002-7739-4306; Schilling,
   Marcel/0000-0002-3453-7792; Zipp, Frauke/0000-0002-1231-1928; Lill,
   Christina/0000-0002-2805-1307; Bertram, Lars/0000-0002-0108-124X;
   Martinez, Maria/0000-0003-2180-4537; Wood, Nicholas/0000-0002-9500-3348;
   Latourelle, Jeanne/0000-0002-4218-9572; Myers,
   Richard/0000-0002-8365-2674; Burns, Gully/0000-0003-1493-865X
FU Michael J. Fox Foundation for Parkinson's Disease (MJFF); Cure
   Alzheimer's Fund (CAF); National Alliance for Research on Schizophrenia
   and Depression (NARSAD); Prize4Life; EMD Serono; Deutscher Akademischer
   Austauschdienst (DAAD); Fidelity Biosciences Research Initiative (FBRI);
   German Ministry for Education and Research (BMBF); Tufts Clinical and
   Translational Science Institute (Tufts CTSI); National Institute of
   Health/National Center for Research Resources [UL1 RR025752]; Michael J.
   Fox Foundation; Edmond J. Safra Michael J. Fox Foundation Global
   Genetics Consortium Initiative; NIH [R01 NS 036960, R01CA141668,
   R01NS37167, 2R01 ES10751]; National Institute on Aging, National
   Institute of Neurological Disorders and Stroke, National Institute of
   Environmental Health Sciences, National Human Genome Research Institute,
   National Institutes of Health, Department of Health and Human Services
   [Z01 AG000949-02, Z01-ES101986]; U.S. Department of Defense
   [W81XWH-09-2-0128]; Volkswagen Foundation; Hermann and Lilly Schilling
   Foundation; Alnylam Pharmaceuticals; Medtronic; NorthShore University
   Health System; Cephalon; Merck-Serono; Novartis; Eisai; Mayo Clinic;
   deCODE
FX The main funding for this study was provided by the Michael J. Fox
   Foundation for Parkinson's Disease (MJFF) with additional financial
   support by the Cure Alzheimer's Fund (CAF), the National Alliance for
   Research on Schizophrenia and Depression (NARSAD), Prize4Life, and EMD
   Serono (all to L Bertram). CM Lill was supported by a fellowship from
   the Deutscher Akademischer Austauschdienst (DAAD) and Fidelity
   Biosciences Research Initiative (FBRI). L Bertram is also supported by
   the German Ministry for Education and Research (BMBF). JPA Ioannidis was
   supported through the Tufts Clinical and Translational Science Institute
   (Tufts CTSI) under funding from the National Institute of
   Health/National Center for Research Resources (UL1 RR025752). Points of
   view or opinions in this paper are those of the authors and do not
   necessarily represent the official position or policies of the Tufts
   CTSI. M Sharma was supported by the Michael J. Fox Foundation. The
   NeuroGenetics Research Consortium GWAS [15] was funded by the Edmond J.
   Safra Michael J. Fox Foundation Global Genetics Consortium Initiative
   and NIH R01 NS 036960. The work of the International Parkinson's Disease
   Genomics Consortium (IPDGC) was supported in part by the Intramural
   Research Programs of the National Institute on Aging, National Institute
   of Neurological Disorders and Stroke, National Institute of
   Environmental Health Sciences, National Human Genome Research Institute,
   National Institutes of Health, Department of Health and Human Services:
   project numbers Z01 AG000949-02 and Z01-ES101986. In addition the work
   of the IPDGC was supported by the U.S. Department of Defense, award
   number W81XWH-09-2-0128. Portions of the work of the IPDGC utilized the
   high-performance computational capabilities of the Biowulf Linux cluster
   at the National Institutes of Health, Bethesda, Md.
   (http://biowulf.nih.gov). T Foroud received funds from the National
   Institutes of Health (R01CA141668 and R01NS37167). C Klein is the
   recipient of a career development award from the Volkswagen Foundation
   and from the Hermann and Lilly Schilling Foundation. DM Maraganore
   acknowledges active funding support from the National Institutes of
   Health (2R01 ES10751), Alnylam Pharmaceuticals, Medtronic, and
   NorthShore University Health System. The funders had no role in study
   design, data collection and analysis, decision to publish, or
   preparation of the manuscript.; CB Do, N Eriksson, and JY Tung are
   employed by 23andMe and own stock options in the company. MJ Farrer and
   Mayo Foundation received royalties from H. Lundbeck A/S and Isis
   Pharmaceuticals. In addition, MJ Farrer has received an honorarium for a
   seminar at Genzyme. T Gasser has received consultancy fees from Cephalon
   and Merck-Serono, grants from Novartis, payments for lectures including
   service on speakers' bureaus from Boehringer Ingelheim, Merck-Serono,
   UCB, and Valean, and holds patents NGFN2 and KASPP. JA Hardy has
   received consulting fees or honoraria from Eisai and his institute has
   received consulting fees or honoraria from Merck-Serono. DM Maraganore
   has received extramural research funding support from the National
   Institutes of Health (2R01 ES10751), the Michael J. Fox Foundation
   (Linked Efforts to Accelerate Parkinson Solutions Award, Edmond J. Safra
   Global Genetics Consortia Award), and from Alnylam Pharmaceuticals and
   Medtronic (observational studies of Parkinson's disease). DM Maraganore
   has also received intramural research funding support from the Mayo
   Clinic and from NorthShore University Health System. DM Maraganore filed
   a provisional patent for a method to predict Parkinson's disease. This
   provisional patent is unlicensed. He also filed a provisional patent for
   a method to treat neurodegenerative disorders. That provisional patent
   has been licensed to Alnylam Pharmaceuticals and DM Maraganore has
   received royalty payments in total of less than $20,000. K Stefansson
   has received grants from deCODE.
NR 34
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PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD MAR
PY 2012
VL 8
IS 3
AR e1002548
DI 10.1371/journal.pgen.1002548
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 918MV
UT WOS:000302254800024
PM 22438815
ER

PT J
AU Pattaro, C
   Kottgen, A
   Teumer, A
   Garnaas, M
   Boger, CA
   Fuchsberger, C
   Olden, M
   Chen, MH
   Tin, A
   Taliun, D
   Li, M
   Gao, XY
   Gorski, M
   Yang, Q
   Hundertmark, C
   Foster, MC
   O'Seaghdha, CM
   Glazer, N
   Isaacs, A
   Liu, CT
   Smith, AV
   O'Connell, JR
   Struchalin, M
   Tanaka, T
   Li, G
   Johnson, AD
   Gierman, HJ
   Feitosa, M
   Hwang, SJ
   Atkinson, EJ
   Lohman, K
   Cornelis, MC
   Johansson, A
   Tonjes, A
   Dehghan, A
   Chouraki, V
   Holliday, EG
   Sorice, R
   Kutalik, Z
   Lehtimaki, T
   Esko, T
   Deshmukh, H
   Ulivi, S
   Chu, AY
   Murgia, F
   Trompet, S
   Imboden, M
   Kollerits, B
   Pistis, G
   Harris, TB
   Launer, LJ
   Aspelund, T
   Eiriksdottir, G
   Mitchell, BD
   Boerwinkle, E
   Schmidt, H
   Cavalieri, M
   Rao, M
   Hu, FB
   Demirkan, A
   Oostra, BA
   de Andrade, M
   Turner, ST
   Ding, JZ
   Andrews, JS
   Freedman, BI
   Koenig, W
   Illig, T
   Doring, A
   Wichmann, HE
   Kolcic, I
   Zemunik, T
   Boban, M
   Minelli, C
   Wheeler, HE
   Igl, W
   Zaboli, G
   Wild, SH
   Wright, AF
   Campbell, H
   Ellinghaus, D
   Nothlings, U
   Jacobs, G
   Biffar, R
   Endlich, K
   Ernst, F
   Homuth, G
   Kroemer, HK
   Nauck, M
   Stracke, S
   Volker, U
   Volzke, H
   Kovacs, P
   Stumvoll, M
   Magi, R
   Hofman, A
   Uitterlinden, AG
   Rivadeneira, F
   Aulchenko, YS
   Polasek, O
   Hastie, N
   Vitart, V
   Helmer, C
   Wang, JJ
   Ruggiero, D
   Bergmann, S
   Kahonen, M
   Viikari, J
   Nikopensius, T
   Province, M
   Ketkar, S
   Colhoun, H
   Doney, A
   Robino, A
   Giulianini, F
   Kramer, BK
   Portas, L
   Ford, I
   Buckley, BM
   Adam, M
   Thun, GA
   Paulweber, B
   Haun, M
   Sala, C
   Metzger, M
   Mitchell, P
   Ciullo, M
   Kim, SK
   Vollenweider, P
   Raitakari, O
   Metspalu, A
   Palmer, C
   Gasparini, P
   Pirastu, M
   Jukema, JW
   Probst-Hensch, NM
   Kronenberg, F
   Toniolo, D
   Gudnason, V
   Shuldiner, AR
   Coresh, J
   Schmidt, R
   Ferrucci, L
   Siscovick, DS
   van Duijn, CM
   Borecki, I
   Kardia, SLR
   Liu, YM
   Curhan, GC
   Rudan, I
   Gyllensten, U
   Wilson, JF
   Franke, A
   Pramstaller, PP
   Rettig, R
   Prokopenko, I
   Witteman, JCM
   Hayward, C
   Ridker, P
   Parsa, A
   Bochud, M
   Heid, IM
   Goessling, W
   Chasman, DI
   Kao, WHL
   Fox, CS
AF Pattaro, Cristian
   Koettgen, Anna
   Teumer, Alexander
   Garnaas, Maija
   Boeger, Carsten A.
   Fuchsberger, Christian
   Olden, Matthias
   Chen, Ming-Huei
   Tin, Adrienne
   Taliun, Daniel
   Li, Man
   Gao, Xiaoyi
   Gorski, Mathias
   Yang, Qiong
   Hundertmark, Claudia
   Foster, Meredith C.
   O'Seaghdha, Conall M.
   Glazer, Nicole
   Isaacs, Aaron
   Liu, Ching-Ti
   Smith, Albert V.
   O'Connell, Jeffrey R.
   Struchalin, Maksim
   Tanaka, Toshiko
   Li, Guo
   Johnson, Andrew D.
   Gierman, Hinco J.
   Feitosa, Mary
   Hwang, Shih-Jen
   Atkinson, Elizabeth J.
   Lohman, Kurt
   Cornelis, Marilyn C.
   Johansson, Asa
   Toenjes, Anke
   Dehghan, Abbas
   Chouraki, Vincent
   Holliday, Elizabeth G.
   Sorice, Rossella
   Kutalik, Zoltan
   Lehtimaeki, Terho
   Esko, Tonu
   Deshmukh, Harshal
   Ulivi, Sheila
   Chu, Audrey Y.
   Murgia, Federico
   Trompet, Stella
   Imboden, Medea
   Kollerits, Barbara
   Pistis, Giorgio
   Harris, Tamara B.
   Launer, Lenore J.
   Aspelund, Thor
   Eiriksdottir, Gudny
   Mitchell, Braxton D.
   Boerwinkle, Eric
   Schmidt, Helena
   Cavalieri, Margherita
   Rao, Madhumathi
   Hu, Frank B.
   Demirkan, Ayse
   Oostra, Ben A.
   de Andrade, Mariza
   Turner, Stephen T.
   Ding, Jingzhong
   Andrews, Jeanette S.
   Freedman, Barry I.
   Koenig, Wolfgang
   Illig, Thomas
   Doering, Angela
   Wichmann, H. -Erich
   Kolcic, Ivana
   Zemunik, Tatijana
   Boban, Mladen
   Minelli, Cosetta
   Wheeler, Heather E.
   Igl, Wilmar
   Zaboli, Ghazal
   Wild, Sarah H.
   Wright, Alan F.
   Campbell, Harry
   Ellinghaus, David
   Nothlings, Ute
   Jacobs, Gunnar
   Biffar, Reiner
   Endlich, Karlhans
   Ernst, Florian
   Homuth, Georg
   Kroemer, Heyo K.
   Nauck, Matthias
   Stracke, Sylvia
   Voelker, Uwe
   Voelzke, Henry
   Kovacs, Peter
   Stumvoll, Michael
   Magi, Reedik
   Hofman, Albert
   Uitterlinden, Andre G.
   Rivadeneira, Fernando
   Aulchenko, Yurii S.
   Polasek, Ozren
   Hastie, Nick
   Vitart, Veronique
   Helmer, Catherine
   Wang, Jie Jin
   Ruggiero, Daniela
   Bergmann, Sven
   Kaehoenen, Mika
   Viikari, Jorma
   Nikopensius, Tiit
   Province, Michael
   Ketkar, Shamika
   Colhoun, Helen
   Doney, Alex
   Robino, Antonietta
   Giulianini, Franco
   Kraemer, Bernhard K.
   Portas, Laura
   Ford, Ian
   Buckley, Brendan M.
   Adam, Martin
   Thun, Gian-Andri
   Paulweber, Bernhard
   Haun, Margot
   Sala, Cinzia
   Metzger, Marie
   Mitchell, Paul
   Ciullo, Marina
   Kim, Stuart K.
   Vollenweider, Peter
   Raitakari, Olli
   Metspalu, Andres
   Palmer, Colin
   Gasparini, Paolo
   Pirastu, Mario
   Jukema, J. Wouter
   Probst-Hensch, Nicole M.
   Kronenberg, Florian
   Toniolo, Daniela
   Gudnason, Vilmundur
   Shuldiner, Alan R.
   Coresh, Josef
   Schmidt, Reinhold
   Ferrucci, Luigi
   Siscovick, David S.
   van Duijn, Cornelia M.
   Borecki, Ingrid
   Kardia, Sharon L. R.
   Liu, Yongmei
   Curhan, Gary C.
   Rudan, Igor
   Gyllensten, Ulf
   Wilson, James F.
   Franke, Andre
   Pramstaller, Peter P.
   Rettig, Rainer
   Prokopenko, Inga
   Witteman, Jacqueline C. M.
   Hayward, Caroline
   Ridker, Paul
   Parsa, Afshin
   Bochud, Murielle
   Heid, Iris M.
   Goessling, Wolfram
   Chasman, Daniel I.
   Kao, W. H. Linda
   Fox, Caroline S.
CA CARDIoGRAM Consortium
   ICBP Consortium
   CARe Consortium
   WTCCC2
TI Genome-Wide Association and Functional Follow-Up Reveals New Loci for
   Kidney Function
SO PLOS GENETICS
LA English
DT Article
ID GLOMERULAR-FILTRATION-RATE; RISK POPULATION COHORTS; GENE-EXPRESSION;
   SERUM CREATININE; COLLABORATIVE METAANALYSIS; HIGHER ALBUMINURIA;
   DISEASE; ZEBRAFISH; ORGANIZATION; VARIANTS
AB Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genomewide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.
C1 [Pattaro, Cristian; Taliun, Daniel; Minelli, Cosetta; Pramstaller, Peter P.] Univ Lubeck, European Acad Bozen Bolzano EURAC, Inst Med Genet, Bolzano, Italy.
   [Pattaro, Cristian; Taliun, Daniel; Minelli, Cosetta; Pramstaller, Peter P.] Univ Lubeck, Affiliated Inst, Bolzano, Italy.
   [Koettgen, Anna; Tin, Adrienne; Li, Man; Coresh, Josef; Kao, W. H. Linda] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
   [Koettgen, Anna; Hundertmark, Claudia] Freiburg Univ Clin, Div Renal, Freiburg, Germany.
   [Teumer, Alexander; Ernst, Florian; Homuth, Georg; Voelker, Uwe] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany.
   [Garnaas, Maija] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Genet, Boston, MA 02115 USA.
   [Boeger, Carsten A.] Univ Med Ctr Regensburg, Dept Internal Med 2, Regensburg, Germany.
   [Fuchsberger, Christian] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
   [Olden, Matthias] Univ Hosp Regensburg, Dept Internal Med 2, Regensburg, Germany.
   [Olden, Matthias] Regensburg Univ Med Ctr, Dept Epidemiol & Prevent Med, Regensburg, Germany.
   [Chen, Ming-Huei] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
   [Chen, Ming-Huei; Yang, Qiong; Liu, Ching-Ti] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
   [Gao, Xiaoyi; Feitosa, Mary; Province, Michael; Ketkar, Shamika; Borecki, Ingrid] Washington Univ, Sch Med, Div Stat Genom, St Louis, MO USA.
   [Gorski, Mathias; Heid, Iris M.] Univ Hosp Regensburg, Dept Epidemiol & Prevent Med, Regensburg, Germany.
   [Gorski, Mathias; Doering, Angela; Wichmann, H. -Erich; Heid, Iris M.] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 1, Neuherberg, Germany.
   [Foster, Meredith C.; O'Seaghdha, Conall M.; Johnson, Andrew D.; Hwang, Shih-Jen; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
   [Foster, Meredith C.; O'Seaghdha, Conall M.; Johnson, Andrew D.; Hwang, Shih-Jen; Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA.
   [O'Seaghdha, Conall M.] Brigham & Womens Hosp, Div Nephrol, Boston, MA 02115 USA.
   [Curhan, Gary C.] Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA.
   [Glazer, Nicole] Boston Univ, Sch Med, Dept Med, Sect Prevent Med & Epidemiol, Boston, MA 02118 USA.
   [Isaacs, Aaron; Demirkan, Ayse; Oostra, Ben A.; van Duijn, Cornelia M.] Erasmus Univ, Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands.
   [Isaacs, Aaron] Ctr Med Syst Biol, Leiden, Netherlands.
   [Smith, Albert V.; Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Res Inst, Kopavogur, Iceland.
   [Smith, Albert V.; Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
   [O'Connell, Jeffrey R.; Mitchell, Braxton D.; Shuldiner, Alan R.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
   [Struchalin, Maksim] Erasmus Univ, Dept Epidemiol & Biostat, Med Ctr, NL-3000 DR Rotterdam, Netherlands.
   [Struchalin, Maksim] Erasmus Univ, Dept Forens Mol Biol, Med Ctr, Rotterdam, Netherlands.
   [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
   [Li, Guo; Siscovick, David S.] Univ Washington, Seattle, WA 98195 USA.
   [Gierman, Hinco J.; Kim, Stuart K.] Stanford Univ, Dept Dev Biol, Stanford, CA 94305 USA.
   [Atkinson, Elizabeth J.; de Andrade, Mariza] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA.
   [Lohman, Kurt; Liu, Yongmei] Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA.
   [Cornelis, Marilyn C.; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
   [Johansson, Asa; Igl, Wilmar; Zaboli, Ghazal; Gyllensten, Ulf] Uppsala Univ, Rudbeck Lab, Uppsala, Sweden.
   [Toenjes, Anke; Stumvoll, Michael] Univ Leipzig, Dept Med, Leipzig, Germany.
   [Toenjes, Anke; Stumvoll, Michael] Univ Leipzig, IFB Adipos Dis, Leipzig, Germany.
   [Chouraki, Vincent] Inst Pasteur, Inserm UMR744, F-59019 Lille, France.
   [Holliday, Elizabeth G.] Univ Newcastle, Sch Med & Publ Hlth, Ctr Clin Epidemiol & Biostat, Newcastle, NSW 2300, Australia.
   [Holliday, Elizabeth G.] Hunter Med Res Inst, Ctr Informat Based Med, Newcastle, NSW, Australia.
   [Sorice, Rossella; Ruggiero, Daniela; Ciullo, Marina] Inst Genet & Biophys Adriano Buzzati Traverso CNR, Naples, Italy.
   [Kutalik, Zoltan] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland.
   [Kutalik, Zoltan; Bergmann, Sven] Swiss Inst Bioinformat, Lausanne, Switzerland.
   [Lehtimaeki, Terho] Univ Tampere, Dept Clin Chem, FIN-33101 Tampere, Finland.
   [Lehtimaeki, Terho] Tampere Univ Hosp, Ctr Lab Med Tampere Finn Medi 2, Tampere, Finland.
   [Esko, Tonu; Magi, Reedik; Metspalu, Andres] EGCUT, Tartu, Estonia.
   [Esko, Tonu; Nikopensius, Tiit; Metspalu, Andres] Univ Tartu, Estonian Bioctr, EE-50090 Tartu, Estonia.
   [Esko, Tonu; Nikopensius, Tiit; Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia.
   [Doney, Alex] Univ Dundee, Clin Res Ctr, Ninewells Hosp, Wellcome Trust Ctr Mol Med,NHS Tayside, Dundee, Scotland.
   [Ulivi, Sheila] Inst Maternal & Child Hlth IRCCS Burlo Garofo, Trieste, Italy.
   [Murgia, Federico; Portas, Laura; Pirastu, Mario] Inst Populat Genet CNR, Sassari, Italy.
   [Trompet, Stella; Jukema, J. Wouter] Leiden Univ, Dept Cardiol, Med Ctr, Leiden, Netherlands.
   [Imboden, Medea; Adam, Martin; Thun, Gian-Andri; Probst-Hensch, Nicole M.] Swiss Trop & Publ Hlth Inst, Unit Chron Dis Epidemiol, Basel, Switzerland.
   [Kollerits, Barbara; Haun, Margot; Kronenberg, Florian] Innsbruck Med Univ, Div Genet Epidemiol, Innsbruck, Austria.
   [Pistis, Giorgio; Sala, Cinzia; Toniolo, Daniela] Ist Sci San Raffaele, Div Genet & Cell Biol, I-20132 Milan, Italy.
   [Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
   [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA.
   [Schmidt, Helena] Med Univ Graz, Austrian Stroke Prevent Study, Inst Mol Biol & Biochem, Graz, Austria.
   [Schmidt, Helena] Med Univ Graz, Dept Neurol, Graz, Austria.
   [Cavalieri, Margherita; Schmidt, Reinhold] Med Univ Graz, Austrian Stroke Prevent Study, Univ Clin Neurol, Dept Special Neurol, Graz, Austria.
   [Rao, Madhumathi] Tufts Univ, Sch Med, Tufts Med Ctr, Tufts Evidence Practice Ctr,Div Nephrol, Boston, MA 02111 USA.
   [Turner, Stephen T.] Mayo Clin, Dept Internal Med, Div Nephrol & Hypertens, Rochester, MN USA.
   [Ding, Jingzhong] Wake Forest Sch Med, Dept Internal Med Geriatr, Winston Salem, NC USA.
   [Andrews, Jeanette S.] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
   [Freedman, Barry I.] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA.
   [Koenig, Wolfgang] Univ Ulm Klinikum, Abt Innere 2, Ulm, Germany.
   [Illig, Thomas; Doering, Angela] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.
   [Wichmann, H. -Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
   [Wichmann, H. -Erich] Klinikum Grosshadern, Neuherberg, Germany.
   [Kolcic, Ivana; Zemunik, Tatijana; Boban, Mladen] Univ Split, Sch Med, Croatian Ctr Global Hlth, Split, Croatia.
   [Wheeler, Heather E.; Kim, Stuart K.] Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
   [Wheeler, Heather E.] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
   [Wild, Sarah H.; Campbell, Harry; Rudan, Igor; Wilson, James F.] Univ Edinburgh, Sch Med, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
   [Wright, Alan F.; Hastie, Nick; Vitart, Veronique; Hayward, Caroline] Western Gen Hosp, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland.
   [Ellinghaus, David; Nothlings, Ute; Jacobs, Gunnar; Franke, Andre] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany.
   [Nothlings, Ute; Jacobs, Gunnar] Univ Hosp Schleswig Holstein, Popgen Biobank, Kiel, Germany.
   [Biffar, Reiner] Ernst Moritz Arndt Univ Greifswald, Clin Prosthodont Dent Gerostomatol & Mat Sci, Greifswald, Germany.
   [Endlich, Karlhans] Ernst Moritz Arndt Univ Greifswald, Inst Anat & Cell Biol, Greifswald, Germany.
   [Kroemer, Heyo K.] Ernst Moritz Arndt Univ Greifswald, Inst Pharmacol, Greifswald, Germany.
   [Nauck, Matthias] Ernst Moritz Arndt Univ Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany.
   [Stracke, Sylvia] Ernst Moritz Arndt Univ Greifswald, Clin Internal Med A, Greifswald, Germany.
   [Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany.
   [Kovacs, Peter] Univ Leipzig, Dept Med, Leipzig, Germany.
   [Magi, Reedik; Prokopenko, Inga] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
   [Magi, Reedik; Prokopenko, Inga] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
   [Uitterlinden, Andre G.; Rivadeneira, Fernando] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands.
   [Polasek, Ozren] Univ Split, Fac Med, Croatian Ctr Global Hlth, Split, Croatia.
   [Helmer, Catherine] Univ Bordeaux 2, INSERM U897, ISPED, F-33076 Bordeaux, France.
   [Wang, Jie Jin; Mitchell, Paul] Univ Sydney, Westmead Hosp, Westmead Millennium Inst, Ctr Vis Res, Sydney, NSW 2006, Australia.
   [Wang, Jie Jin] Univ Melbourne, CERA, Melbourne, Vic, Australia.
   [Kaehoenen, Mika] Univ Tampere, Dept Clin Physiol, FIN-33101 Tampere, Finland.
   [Viikari, Jorma] Univ Turku, Dept Med, Turku, Finland.
   [Robino, Antonietta; Gasparini, Paolo] Univ Trieste, IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy.
   [Kraemer, Bernhard K.] Univ Med Ctr Mannheim, Dept Med 5, Mannheim, Germany.
   [Ford, Ian] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
   [Buckley, Brendan M.] Natl Univ Ireland Univ Coll Cork, Dept Pharmacol & Therapeut, Cork, Ireland.
   [Paulweber, Bernhard] Paracelsus Med Univ, Dept Internal Med 1, Salzburg, Austria.
   [Metzger, Marie] Univ Paris 11, CESP Team 10, Inserm UMRS 1018, Villejuif, France.
   [Vollenweider, Peter] CHU Vaudois, Dept Internal Med, Lausanne, Switzerland.
   [Raitakari, Olli] Univ Turku, Turku Univ Hosp, Dept Clin Physiol, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.
   [Palmer, Colin] Univ Dundee, Ninewells Hosp & Med Sch, Biomed Res Inst, Dundee DD1 9SY, Scotland.
   [Jukema, J. Wouter] ICIN, Utrecht, Netherlands.
   [Jukema, J. Wouter] Einthoven Lab Expt Vasc Med, Leiden, Netherlands.
   [Jukema, J. Wouter] Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands.
   [Shuldiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21218 USA.
   [Coresh, Josef; Kao, W. H. Linda] Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
   [Kardia, Sharon L. R.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
   [Rettig, Rainer] Ernst Moritz Arndt Univ Greifswald, Inst Physiol, Greifswald, Germany.
   [Parsa, Afshin] Univ Maryland, Sch Med, Div Nephrol, Baltimore, MD 21201 USA.
   [Bochud, Murielle] Univ Lausanne, CH-1066 Epalinges, Switzerland.
   [Bochud, Murielle] CHU Vaudois, Univ Inst Social & Prevent Med, Epalinges, Switzerland.
   [Goessling, Wolfram] Brigham & Womens Hosp, Dept Internal Med, Div Genet, Boston, MA USA.
   [Goessling, Wolfram] Brigham & Womens Hosp, Dept Internal Med, Div Gastroenterol, Boston, MA USA.
   [Goessling, Wolfram] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
   [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA USA.
RP Pattaro, C (reprint author), Univ Lubeck, European Acad Bozen Bolzano EURAC, Inst Med Genet, Bolzano, Italy.
EM wkao@jhsph.edu; foxca@nhlbi.nih.gov
RI Colaus, PsyColaus/K-6607-2013; Aulchenko, Yurii/M-8270-2013; Yang,
   Qiong/G-5438-2014; Pramstaller, Peter/C-2357-2008; Johansson,
   Asa/G-5270-2011; EHRET, Georg/A-9532-2009; Wang, Jie Jin/P-1499-2014;
   Kronenberg, Florian/B-1736-2008; Mitchell, Paul/P-1498-2014; HELMER,
   Catherine/I-6581-2015; Gudnason, Vilmundur/K-6885-2015; Wilson, James
   F/A-5704-2009; Kottgen, Anna/D-2920-2012; Palmer, Colin/C-7053-2008;
   Aspelund, Thor/C-5983-2008; Rudan, Igor/I-1467-2012; Li,
   Guo/E-5613-2012; Fuchsberger, Christian/C-9646-2010; Ellinghaus,
   David/G-4467-2012; Cavalieri, Margherita/G-8053-2012; Nothlings,
   Ute/B-2713-2010; Endlich, Karlhans/G-5485-2013; Johnson,
   Andrew/G-6520-2013; Ulivi, Sheila/H-3700-2013; Polasek,
   Ozren/B-6002-2011; Rivadeneira, Fernando/O-5385-2015; Prokopenko,
   Inga/H-3241-2014; Smith, Albert/K-5150-2015; ruggiero,
   daniela/K-5638-2016; Study, GoDARTS/K-9448-2016; Bochud,
   Murielle/A-3981-2010; Hayward, Caroline/M-8818-2016; Franke,
   Andre/B-2151-2010; Boban, Mladen/E-2777-2017; Kolcic, Ivana/E-2713-2017;
   Feitosa, Mary/K-8044-2012
OI Aulchenko, Yurii/0000-0002-7899-1575; Johansson,
   Asa/0000-0002-2915-4498; EHRET, Georg/0000-0002-5730-0675; Wang, Jie
   Jin/0000-0001-9491-4898; Kronenberg, Florian/0000-0003-2229-1120;
   HELMER, Catherine/0000-0002-5169-7421; Gudnason,
   Vilmundur/0000-0001-5696-0084; Wilson, James F/0000-0001-5751-9178;
   Palmer, Colin/0000-0002-6415-6560; Aspelund, Thor/0000-0002-7998-5433;
   Rudan, Igor/0000-0001-6993-6884; Ulivi, Sheila/0000-0003-3606-835X;
   Goessling, Wolfram/0000-0001-9972-1569; Klein,
   Ronald/0000-0002-4428-6237; Colhoun, Helen/0000-0002-8345-3288;
   Mitchell, Braxton/0000-0003-4920-4744; Dehghan,
   Abbas/0000-0001-6403-016X; Magi, Reedik/0000-0002-2964-6011; Chouraki,
   Vincent/0000-0002-4698-1794; Fuchsberger, Christian/0000-0002-5918-8947;
   Esko, Tonu/0000-0003-1982-6569; Thun, Gian Andri/0000-0003-4436-3455;
   Wheeler, Heather/0000-0003-1365-9667; Polasek,
   Ozren/0000-0002-5765-1862; Rivadeneira, Fernando/0000-0001-9435-9441;
   Prokopenko, Inga/0000-0003-1624-7457; Smith, Albert/0000-0003-1942-5845;
   ruggiero, daniela/0000-0003-3898-7827; Bochud,
   Murielle/0000-0002-5727-0218; Hayward, Caroline/0000-0002-9405-9550;
   Franke, Andre/0000-0003-1530-5811; Kolcic, Ivana/0000-0001-7918-6052;
   Feitosa, Mary/0000-0002-0933-2410
FU NIH [N01-AG-1-2100, R01 AG18728, R01 HL088119, U01 GM074518-04, U01
   HL072515-06, U01 HL084756, NIH K12RR023250, HHSN268200625226C,
   5R01HL08770003, 5R01HL08821502, HHSN268200782096C, 5R01HL08770002]; NIA
   (the Icelandic Heart Association) [N01AG62101, N01AG62103, N01AG62106,
   1R01AG032098-01A1]; Althingi (the Icelandic Parliament); University of
   Maryland General Clinical Research Center [M01 RR 16500]; Baltimore
   Veterans Administration Medical Center Geriatrics Research and Education
   Clinical Center; Paul Beeson Physician Faculty Scholars in Aging
   Program; Austrian Science Fund (FWF) [P20545-P05, P13180]; The Medical
   University of Graz; National Human Genome Research Institute
   [U01HG004402]; German Research Foundation [KO3598/2-1]; NIH (National
   Institute on Aging); National Center for Research Resources
   [M01RR00425]; National Institute of Diabetes and Digestive and Kidney
   Diseases [DK063491, R01DK058845]; Netherlands Organization for
   Scientific Research (NWO; Pioneergrant); Erasmus Medical Center; Centre
   for Medical Systems Biology (CMSB); Netherlands Kidney Foundation;
   NHLBI; NIDDK [5R01DK07568102, 5R01DK06833603]; National Heart, Lung, and
   Blood Institute's Framingham Heart Study [N01-HC-25195]; Affymetrix for
   genotyping services [N02-HL-6-4278]; Department of Medicine at Boston
   University School of Medicine and Boston Medical Center; National Heart,
   Lung, and Blood Institute of the National Institutes of Health [R01
   HL-87660]; National Institutes of Aging; Children's Hospital, Boston, US
   [1 R01 DK075787-01A1]; German National Genome Research Net NGFN2;
   NGFNplus [01GS0823, 01GS0834]; Munich Center of Health Sciences (MC
   Health); Else Kroner-Fresenius-Stiftung [P48/08//A11/08]; Regensburg
   University Medical Center, Germany; Helmholtz Zentrum Munchen, German
   Research Center for Environmental Health; German Federal Ministry of
   Education and Research; State of Bavaria; University of Regensburg for
   the Department of Epidemiology and Preventive Medicine at the Regensburg
   University Medical Center; NHS/HPFS; National Institute of Dental and
   Craniofacial Research [U01DE018993, U01DE018903]; Gene
   Environment-Association Studies (GENEVA) under NIH Genes; Environment
   and Health Initiative (GEI); NIH GEI [U01HG04424, U01HG004438]; Johns
   Hopkins University Center for Inherited Disease Research; National
   Cancer Institute [P01CA087969, P01CA055075, CA 047988]; Medical Research
   Council UK; Ministry of Science, Education, and Sport of the Republic of
   Croatia [108-1080315-0302]; Ministry of Health and Department of
   Educational Assistance; University and Research of the Autonomous
   Province of Bolzano; South Tyrolean Sparkasse Foundation; European Union
   [LSHG-CT-2006-018947]; Swedish Natural Sciences Research Council;
   European Union through EUROSPAN [LSHG-CT-2006-018947]; Foundation for
   Strategic Research (SSF); Linneaus Centre for Bioinformatics (LCB); NHS
   [DK66574]; Chief Scientist Office of the Scottish Government; Royal
   Society; German Ministry of Education and Research (BMBF) through the
   National Genome Research Network (NGFN); Ministry of Science, Commerce,
   and Transportation of the State of Schleswig-Holstein; DFG excellence
   cluster "Inflammation at Interfaces"; German Research Council [KFO-152];
   IFB (Integrated Research and Treatment Center) AdiposityDiseases
   [K7-37]; European Community [FP7/2007-2013]; ENGAGE
   [HEALTH-F4-2007-201413]; European Commission under a Marie Curie
   Intra-European; Netherlands Organisation of Scientific Research NWO
   Investments [175.010.2005.011, 911-03-012]; Research Institute for
   Diseases [014-93-015, RIDE2]; Netherlands Genomics Initiative
   (NGI)/Netherlands Consortium for Healthy Aging (NCHA) [050-060-810];
   Erasmus University, Rotterdam; The Netherlands Organization for the
   Health Research and Development (ZonMw); Research Institute for Diseases
   in the Elderly (RIDE); Ministry of Education, Culture, and Science;
   Ministry for Health, Welfare, and Sports, the European Commission (DG
   XII); Municipality of Rotterdam; German Bundesministerium fuer Forschung
   und Technology [01 AK 803 A-H, 01 IG 07015 G]; NWO [918-76-619]; Federal
   Ministry of Education and Research [01ZZ9603, 01ZZ0103, 01ZZ0403,
   03ZIK012]; Ministry of Cultural Affairs; Social Ministry of the Federal
   State of Mecklenburg-West Pomerania; Siemens Healthcare, Erlangen,
   Germany; Federal State of Mecklenburg-West Pomerania; Donald W. Reynolds
   Foundation; Fondation Leducq; Amgen; National Foundation for Alzheimer's
   disease; Institut Pasteur de Lille; Centre National de Genotypage;
   Fondation pour la Recherche Medicale; Caisse Nationale Maladie des
   Travailleurs Salaries; MGEN; Institut de la Longevite; Agence Francaise
   de Securite Sanitaire des Produits de Sante; Aquitaine and Bourgogne
   Regional Councils; Fondation de France; Ministry of Research/INSERM
   "Cohortes et collections de donnees biologiques; Australian RADGAC;
   Australian National Health; Medical Research Council, Canberra Australia
   [974159, 211069, 991407, 457349]; Australian National Health and Medical
   Research Council [512423, 475604, 529912]; Wellcome Trust, UK; Wellcome
   Trust Case Control Consortium 2 [085475/B/08/Z, 085475/08/Z]; Australian
   National Health and Medical Research Council; GlaxoSmithKline; Faculty
   of Biology and Medicine of Lausanne; Swiss National Science Foundation
   [33CSCO-122661, 33CSCO-108796, 3247BO-104283, 3247BO-104288,
   3247BO-104284, 3247-065896, 3100-059302, 3200-052720, 3200-042532,
   4026-028099]; Swiss School of Public Health Plus (SSPH+); Academy of
   Finland [117797, 121584, 126925]; Social Insurance Institution of
   Finland; University Hospital Medical; University Hospitals; Finnish
   Foundation of Cardiovascular Research; EGCUT [201413 ENGAGE, 212111
   BBMRI, 205419 ECOGENE, 245536 OPENGENE]; Estonian Government
   [SF0180142s08]; European Union through the European Regional
   Development; Centre of Excellence in Genomics; Wellcome Trust United
   Kingdom Type 2 Diabetes Case Control Collection; Chief Scientist Office;
   Scottish Health Informatics Programme (SHIP); Telethon; FVG region;
   Fondo Trieste; EU [Vasoplus-037254]; Italian Ministry of Universities
   [FIRB -RBIN064YAT]; Assessorato Ricerca Regione Campania; Ente Parco
   Nazionale del Cilento e Vallo di Diano; Fondazione Banco di Napoli;
   Compagnia di San Paolo, Torino, Italy; Cariplo Fundation, Milano, Italy;
   Italian Ministry of Health Progetto Finalizzato; AstraZeneca; Italian
   Ministry of Education, University, and Research (MIUR)
   [5571/DSPAR/2002]; FIRB [718/Ric/2005]; Bristol-Myers Squibb, USA;
   Federal Office for Forest, Environment, and Landscape; Federal Office of
   Public Health, the Federal Office of Roads and Transport; canton's
   government of Aargau; Basel-Stadt; Basel-Land; Geneva; Luzern; Ticino;
   Zurich; Swiss Lung League; canton's Lung League of Basel Stadt/Basel
   Landschaft; Kamillo Eisner Stiftung; Genomics of Lipid-associated
   Disorders - GOLD; Austrian Genome Research Programme GEN-AU; AFAR/EMF;
   Stanford Dean's postdoctoral fellowship; NHGRI; NIGMS
FX The AGES study has been funded by NIH contract N01-AG-1-2100, the NIA
   Intramural Research Program, Hjartavernd (the Icelandic Heart
   Association), and the Althingi (the Icelandic Parliament). The Amish
   study was supported by grants and contracts from the NIH including R01
   AG18728 (Amish Longevity Study), R01 HL088119 (Amish Calcification
   Study), U01 GM074518-04 (PAPI Study), U01 HL072515-06 (HAPI Study), U01
   HL084756 and NIH K12RR023250 (University of Maryland MCRDP), the
   University of Maryland General Clinical Research Center, grant M01 RR
   16500, the Baltimore Veterans Administration Medical Center Geriatrics
   Research and Education Clinical Center, and the Paul Beeson Physician
   Faculty Scholars in Aging Program. The ASPS research reported in this
   article was funded by the Austrian Science Fund (FWF) grant number
   P20545-P05 and P13180. The Medical University of Graz supported the
   databank of the ASPS. The Atherosclerosis Risk in Communities Study is
   carried out as a collaborative study supported by National Heart, Lung,
   and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C,
   HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
   HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C),
   R01HL087641, R01HL59367, and R01HL086694; National Human Genome Research
   Institute contract U01HG004402; and National Institutes of Health
   contract HHSN268200625226C. Infrastructure was partly supported by Grant
   Number, a component of the National Institutes of Health and NIH Roadmap
   for Medical Research. A Kottgen and C Hundertmark were supported by the
   grant KO3598/2-1 (Emmy Noether Programme) of the German Research
   Foundation. The BLSA was supported in part by the Intramural Research
   Program of the NIH (National Institute on Aging). The CHS research
   reported in this article was supported by contract numbers N01-HC-85079
   through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222,
   N01-HC-75150, N01-HC-45133, and grant numbers U01 HL080295 and R01
   HL087652 from the National Heart, Lung, and Blood Institute, with
   additional contribution from the National Institute of Neurological
   Disorders and Stroke. A full list of principal CHS investigators and
   institutions can be found at http://www.chs-nhlbi.org/pi.htm. DNA
   handling and genotyping was supported in part by National Center for
   Research Resources grant M01RR00425 to the Cedars-Sinai General Clinical
   Research Center Genotyping core and National Institute of Diabetes and
   Digestive and Kidney Diseases grant DK063491 to the Southern California
   Diabetes Endocrinology Research Center. The ERF study was supported by
   grants from the Netherlands Organization for Scientific Research (NWO;
   Pioneergrant), Erasmus Medical Center, the Centre for Medical Systems
   Biology (CMSB), and the Netherlands Kidney Foundation. The Family Heart
   Study (FHS) work was supported in part by NIH grants 5R01HL08770003,
   5R01HL08821502 (M Province) from the NHLBI and 5R01DK07568102,
   5R01DK06833603 from the NIDDK (I Borecki). The Framingham Heart Study
   research reported in this paper was conducted in part using data and
   resources from the Framingham Heart Study of the National Heart Lung and
   Blood Institute of the National Institutes of Health and Boston
   University School of Medicine. The analyses reflect intellectual input
   and resource development from the Framingham Heart Study investigators
   participating in the SNP Health Association Resource (SHARe) project.
   This work was partially supported by the National Heart, Lung, and Blood
   Institute's Framingham Heart Study (Contract No.; N01-HC-25195) and its
   contract with Affymetrix for genotyping services (Contract No.
   N02-HL-6-4278). A portion of this research utilized the Linux Cluster
   for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans
   Endowment of the Department of Medicine at Boston University School of
   Medicine and Boston Medical Center. The GENOA research was partially
   supported by the National Heart, Lung, and Blood Institute of the
   National Institutes of Health R01 HL-87660. The Health Aging and Body
   Composition Study (Health ABC) was funded by the National Institutes of
   Aging. This research was supported by NIA contracts N01AG62101,
   N01AG62103, and N01AG62106. The GWAS was funded by NIA grant
   1R01AG032098-01A1 to Wake Forest University Health Sciences and
   genotyping services were provided by the Center for Inherited Disease
   Research (CIDR). CIDR is fully funded through a federal contract from
   the National Institutes of Health to The Johns Hopkins University,
   contract number HHSN268200782096C. This research was supported in part
   by the Intramural Research Program of the NIH, National Institute on
   Aging. For the KORA F3 and F4 studies, the genetic epidemiological work
   was funded by the NIH subcontract from the Children's Hospital, Boston,
   US, (HE Wichmann, IM Heid, prime grant 1 R01 DK075787-01A1), the German
   National Genome Research Net NGFN2 and NGFNplus (H.E.Wichmann 01GS0823;
   WK project A3, number 01GS0834), the Munich Center of Health Sciences
   (MC Health) as part of LMUinnovativ, and by the Else
   Kroner-Fresenius-Stiftung (P48/08//A11/08; CA Boger, BK Kramer). The
   kidney parameter measurements in F3 were funded by the Else
   Kroner-Fresenius-Stiftung (CA Boger, BK Kramer) and the Regensburg
   University Medical Center, Germany; in F4 by the University of Ulm,
   Germany (W Koenig). Genome-wide genotyping costs in F3 and F4 was in
   part funded by the Else Kroner-Fresenius-Stiftung (CA Boger, BK Kramer).
   De novo genotyping in F3 and F4 was funded by the Else
   Kroner-Fresenius-Stiftung (CA Boger, BK Kramer). The KORA research
   platform and the MONICA Augsburg studies were initiated and financed by
   the Helmholtz Zentrum Munchen, German Research Center for Environmental
   Health, by the German Federal Ministry of Education and Research, and by
   the State of Bavaria. Genotyping was performed in the Genome Analysis
   Center (GAC) of the Helmholtz Zentrum Munchen. The LINUX platform for
   computation was funded by the University of Regensburg for the
   Department of Epidemiology and Preventive Medicine at the Regensburg
   University Medical Center. The NHS/HPFS type 2 diabetes GWAS
   (U01HG004399) is a component of a collaborative project that includes 13
   other GWAS (U01HG004738, U01HG004422, U01HG004402, U01HG004729,
   U01HG004726, U01HG004735, U01HG004415, U01HG004436, U01HG004423,
   U01HG004728, RFAHG006033; National Institute of Dental and Craniofacial
   Research: U01DE018993, U01DE018903) funded as part of the Gene
   Environment-Association Studies (GENEVA) under the NIH Genes,
   Environment and Health Initiative (GEI). Assistance with phenotype
   harmonization and genotype cleaning, as well as with general study
   coordination, was provided by the GENEVA Coordinating Center
   (U01HG004446). Assistance with data cleaning was provided by the
   National Center for Biotechnology Information.; Genotyping was performed
   at the Broad Institute of MIT and Harvard, with funding support from the
   NIH GEI (U01HG04424), and Johns Hopkins University Center for Inherited
   Disease Research, with support from the NIH GEI (U01HG004438) and the
   NIH contract "High-throughput genotyping for studying the genetic
   contributions to human disease'' (HHSN268200782096C). Additional funding
   for the current research was provided by the National Cancer Institute
   (P01CA087969, P01CA055075) and the National Institute of Diabetes and
   Digestive and Kidney Diseases (R01DK058845). We thank the staff and
   participants of the NHS and HPFS for their dedication and commitment.
   The Korcula study was supported through the grants from the Medical
   Research Council UK to H Campbell, AF Wright, and I Rudan and by
   Ministry of Science, Education, and Sport of the Republic of Croatia to
   I Rudan (number 108-1080315-0302). The MICROS study was supported by the
   Ministry of Health and Department of Educational Assistance, University
   and Research of the Autonomous Province of Bolzano, the South Tyrolean
   Sparkasse Foundation, and the European Union framework program 6
   EUROSPAN project (contract no. LSHG-CT-2006-018947). The Northern
   Swedish Population Health Study was supported by grants from the Swedish
   Natural Sciences Research Council, the European Union through the
   EUROSPAN project (contract no. LSHG-CT-2006-018947), the Foundation for
   Strategic Research (SSF), and the Linneaus Centre for Bioinformatics
   (LCB). The NHS renal function and albuminuria work was supported by
   DK66574. Additional funding for the current research was provided by the
   National Cancer Institute (P01CA087969, P01CA055075) and the National
   Institute of Diabetes and Digestive and Kidney Diseases (R01DK058845).
   ORCADES was supported by the Chief Scientist Office of the Scottish
   Government, the Royal Society and the European Union framework program 6
   EUROSPAN project (contract no. LSHG-CT-2006-018947). DNA extractions
   were performed at the Wellcome Trust Clinical Research Facility in
   Edinburgh. The popgen study was supported by the German Ministry of
   Education and Research (BMBF) through the National Genome Research
   Network (NGFN) and the Ministry of Science, Commerce, and Transportation
   of the State of Schleswig-Holstein. The project has also received
   infrastructure support through the DFG excellence cluster "Inflammation
   at Interfaces." The Sorbs study was funded by grants from the German
   Research Council KFO-152 (to M Stumvoll) and the IFB (Integrated
   Research and Treatment Center) AdiposityDiseases (K7-37 to M Stumvoll
   and A Tonjes). We also thank Dr. Knut Krohn (Microarray Core Facility of
   the Interdisciplinary Centre for Clinical Research, University of
   Leipzig, Germany) for providing the genotyping platform. The research of
   Inga Prokopenko is funded in part through the European Community's
   Seventh Framework Programme (FP7/2007-2013), ENGAGE project, grant
   agreement HEALTH-F4-2007-201413. R Magi acknowledges financial support
   from the European Commission under a Marie Curie Intra-European
   Fellowship. For the Rotterdam Study-I and Rotterdam Study-II, the GWAS
   was funded by the Netherlands Organisation of Scientific Research NWO
   Investments (nr. 175.010.2005.011, 911-03-012), the Research Institute
   for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands
   Genomics Initiative (NGI)/Netherlands Consortium for Healthy Aging
   (NCHA) project nr. 050-060-810.; The Rotterdam Study is funded by
   Erasmus Medical Center and Erasmus University, Rotterdam, The
   Netherlands Organization for the Health Research and Development
   (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the
   Ministry of Education, Culture, and Science, the Ministry for Health,
   Welfare, and Sports, the European Commission (DG XII), and the
   Municipality of Rotterdam. The Erasmus Computing Grid, Rotterdam (The
   Netherlands) and the national German MediGRID and Services@MediGRID part
   of the German D-Grid were both funded by the German Bundesministerium
   fuer Forschung und Technology under grants #01 AK 803 A-H and # 01 IG
   07015 G, for access to their grid resources. A Dehghan is supported by
   NWO grant (vici, 918-76-619). The Study of Health in Pomerania (SHIP) is
   part of the Community Medicine Research net of the University of
   Greifswald, Germany, funded by the Federal Ministry of Education and
   Research (grants no. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of
   Cultural Affairs as well as the Social Ministry of the Federal State of
   Mecklenburg-West Pomerania. Genome-wide data have been supported by the
   Federal Ministry of Education and Research (grant no. 03ZIK012) and a
   joint grant from Siemens Healthcare, Erlangen, Germany, and the Federal
   State of Mecklenburg-West Pomerania. The University of Greifswald is a
   member of the 'Center of Knowledge Interchange' program of the Siemens
   AG. The Vis study was supported through the grants from the Medical
   Research Council UK to H Campbell, AF Wright, and I Rudan; and Ministry
   of Science, Education, and Sport of the Republic of Croatia to I Rudan
   (number 108-1080315-0302) and the European Union framework program 6
   EUROSPAN project (contract no. LSHG-CT-2006-018947). The WGHS is
   supported by HL 043851 and HL69757 from the National Heart, Lung, and
   Blood Institute and CA 047988 from the National Cancer Institute, the
   Donald W. Reynolds Foundation and the Fondation Leducq, with
   collaborative scientific support and funding for genotyping provided by
   Amgen. The 3 City Study was supported by the National Foundation for
   Alzheimer's disease and related disorders, the Institut Pasteur de Lille
   and the Centre National de Genotypage. The 3 City Study was performed as
   part of a collaboration between the Institut National de la Sante et de
   la Recherche Medicale (Inserm), the Victor Segalen Bordeaux II
   University and Sanofi-Synthelabo. The Fondation pour la Recherche
   Medicale funded the preparation and initiation of the study. The 3C
   Study was also funded by the Caisse Nationale Maladie des Travailleurs
   Salaries, Direction Generale de la Sante, MGEN, Institut de la
   Longevite, Agence Francaise de Securite Sanitaire des Produits de Sante,
   the Aquitaine and Bourgogne Regional Councils, Fondation de France and
   the joint French Ministry of Research/INSERM "Cohortes et collections de
   donnees biologiques'' programme. Lille Genopole received an
   unconditional grant from Eisai. The Blue Mountains Eye Study (BMES) has
   been supported by the Australian RADGAC grant (1992-94) and Australian
   National Health and Medical Research Council, Canberra Australia (Grant
   Nos: 974159, 211069, 991407, 457349). The GWAS studies of BMES
   population are supported by the Australian National Health and Medical
   Research Council (Grant Nos: 512423, 475604, 529912) and the Wellcome
   Trust, UK (2008), as part of Wellcome Trust Case Control Consortium 2 (A
   Viswanathan, P McGuffin, P Mitchell, F Topouzis, P Foster, grant numbers
   085475/B/08/Z and 085475/08/Z).; EG Holliday and JJ Wang are funded by
   the Australian National Health and Medical Research Council Fellowship
   Schemes. The CoLaus study received financial contributions from
   GlaxoSmithKline, the Faculty of Biology and Medicine of Lausanne, and
   the Swiss National Science Foundation (33CSCO-122661). M Bochud is
   supported by the Swiss School of Public Health Plus (SSPH+). The
   Cardiovascular Risk in Young Finns study (YFS) is supported by the
   Academy of Finland (grant no. 117797, 121584, and 126925), the Social
   Insurance Institution of Finland, University Hospital Medical funds to
   Tampere and Turku University Hospitals, and the Finnish Foundation of
   Cardiovascular Research. The Emil Aaaltonen Foundation (T Lehtimaki).
   EGCUT received support from FP7 grants ((201413 ENGAGE, 212111 BBMRI,
   205419 ECOGENE, 245536 OPENGENE) and also received targeted financing
   from Estonian Government SF0180142s08 and from the European Union
   through the European Regional Development Fund, in the frame of Centre
   of Excellence in Genomics. The research of the FamHS-II was conducted in
   part using data and resources from the NHLBI Family Heart Study
   supported in part by NIH grant 5R01HL08770002. For the GoDARTs study,
   the Wellcome Trust provides support for Wellcome Trust United Kingdom
   Type 2 Diabetes Case Control Collection and the informatics support is
   provided by the Chief Scientist Office, and the Wellcome Trust funded
   Scottish Health Informatics Programme (SHIP). The INGI-Carlantino and
   INGI-FVG studies were supported by grants from Telethon, FVG region, and
   Fondo Trieste. The INGI-Cilento study was supported by grants from the
   EU (Vasoplus-037254), the Italian Ministry of Universities (FIRB
   -RBIN064YAT), the Assessorato Ricerca Regione Campania, the Ente Parco
   Nazionale del Cilento e Vallo di Diano, and the Fondazione Banco di
   Napoli to M Ciullo. The INGI - Val Borbera Study was supported from
   Compagnia di San Paolo, Torino, Italy, the Cariplo Fundation, Milano,
   Italy, and Italian Ministry of Health Progetto Finalizzato 2007 and
   2009. The JUPITER trial and the genotyping were supported by
   AstraZeneca. The Ogliastra Genetic Park (OGP) - Replication Study and
   OGP - Talana study were supported by grants from the Italian Ministry of
   Education, University, and Research (MIUR) no. 5571/DSPAR/2002 and
   (FIRB) D. M. no. 718/Ric/2005. The Prospective Study of Pravastatin in
   the Elderly at Risk (PROSPER) trial was supported by an investigator
   initiated grant from Bristol-Myers Squibb, USA. The study was conducted,
   analyzed, and reported independently of the company. The SAPALDIA study
   was supported by the Swiss National Science Foundation (grants no
   33CSCO-108796, 3247BO-104283, 3247BO-104288, 3247BO-104284, 3247-065896,
   3100-059302, 3200-052720, 3200-042532, 4026-028099), the Federal Office
   for Forest, Environment, and Landscape, the Federal Office of Public
   Health, the Federal Office of Roads and Transport, the canton's
   government of Aargau, Basel-Stadt, Basel-Land, Geneva, Luzern, Ticino,
   Zurich, the Swiss Lung League, the canton's Lung League of Basel
   Stadt/Basel Landschaft, Geneva, Ticino, and Zurich. The SAPHIR-study was
   partially supported by a grant from the Kamillo Eisner Stiftung to B
   Paulweber and by grants from the "Genomics of Lipid-associated Disorders
   - GOLD'' of the "Austrian Genome Research Programme GEN-AU" to F
   Kronenberg. eQTL analysis: HJ Gierman received support from the AFAR/EMF
   postdoctoral fellowship and the Stanford Dean's postdoctoral fellowship.
   HE Wheeler and SK Kim were supported by grants from the NIA, NHGRI and
   NIGMS.
NR 57
TC 76
Z9 76
U1 4
U2 23
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD MAR
PY 2012
VL 8
IS 3
AR e1002584
DI 10.1371/journal.pgen.1002584
PG 15
WC Genetics & Heredity
SC Genetics & Heredity
GA 918MV
UT WOS:000302254800059
PM 22479191
ER

PT J
AU Qayyum, R
   Snively, BM
   Ziv, E
   Nalls, MA
   Liu, YM
   Tang, WH
   Yanek, LR
   Lange, L
   Evans, MK
   Ganesh, S
   Austin, MA
   Lettre, G
   Becker, DM
   Zonderman, AB
   Singleton, AB
   Harris, TB
   Mohler, ER
   Logsdon, BA
   Kooperberg, C
   Folsom, AR
   Wilson, JG
   Becker, LC
   Reiner, AP
AF Qayyum, Rehan
   Snively, Beverly M.
   Ziv, Elad
   Nalls, Michael A.
   Liu, Yongmei
   Tang, Weihong
   Yanek, Lisa R.
   Lange, Leslie
   Evans, Michele K.
   Ganesh, Santhi
   Austin, Melissa A.
   Lettre, Guillaume
   Becker, Diane M.
   Zonderman, Alan B.
   Singleton, Andrew B.
   Harris, Tamara B.
   Mohler, Emile R.
   Logsdon, Benjamin A.
   Kooperberg, Charles
   Folsom, Aaron R.
   Wilson, James G.
   Becker, Lewis C.
   Reiner, Alexander P.
TI A Meta-Analysis and Genome-Wide Association Study of Platelet Count and
   Mean Platelet Volume in African Americans
SO PLOS GENETICS
LA English
DT Article
ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY; GENE-EXPRESSION; CAPPING
   PROTEIN; POPULATION; ACTIVATION; DISEASE; TRAITS; RISK; DIFFERENTIATION
AB Several genetic variants associated with platelet count and mean platelet volume (MPV) were recently reported in people of European ancestry. In this meta-analysis of 7 genome-wide association studies (GWAS) enrolling African Americans, our aim was to identify novel genetic variants associated with platelet count and MPV. For all cohorts, GWAS analysis was performed using additive models after adjusting for age, sex, and population stratification. For both platelet phenotypes, meta-analyses were conducted using inverse-variance weighted fixed-effect models. Platelet aggregation assays in whole blood were performed in the participants of the GeneSTAR cohort. Genetic variants in ten independent regions were associated with platelet count (N = 16,388) with p < 5 x 10(-8) of which 5 have not been associated with platelet count in previous GWAS. The novel genetic variants associated with platelet count were in the following regions (the most significant SNP, closest gene, and p-value): 6p22 (rs12526480, LRRC16A, p = 9.1 x 10(-9)), 7q11 (rs13236689, CD36, p = 2.8 x 10(-9)), 10q21 (rs7896518, JMJD1C, p = 2.3 x 10(-1)2), 11q13 (rs477895, BAD, p = 4.9 x 10(-8)), and 20q13 (rs151361, SLMO2, p = 9.4 x 10(-9)). Three of these loci (10q21, 11q13, and 20q13) were replicated in European Americans (N = 14,909) and one (11q13) in Hispanic Americans (N = 3,462). For MPV (N = 4,531), genetic variants in 3 regions were significant at p, 5610 28, two of which were also associated with platelet count. Previously reported regions that were also significant in this study were 6p21, 6q23, 7q22, 12q24, and 19p13 for platelet count and 7q22, 17q11, and 19p13 for MPV. The most significant SNP in 1 region was also associated with ADP-induced maximal platelet aggregation in whole blood (12q24). Thus through a meta-analysis of GWAS enrolling African Americans, we have identified 5 novel regions associated with platelet count of which 3 were replicated in other ethnic groups. In addition, we also found one region associated with platelet aggregation that may play a potential role in atherothrombosis.
C1 [Qayyum, Rehan; Yanek, Lisa R.; Becker, Diane M.; Becker, Lewis C.] Johns Hopkins Sch Med, GeneSTAR Res Program, Div Gen Internal Med, Baltimore, MD USA.
   [Snively, Beverly M.] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
   [Ziv, Elad] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
   [Nalls, Michael A.; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
   [Liu, Yongmei] Wake Forest Univ, Bowman Gray Sch Med, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC USA.
   [Tang, Weihong; Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
   [Lange, Leslie] Univ N Carolina, Sch Med, Dept Genet, Chapel Hill, NC USA.
   [Evans, Michele K.] NIA, Hlth Dispar Res Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA.
   [Ganesh, Santhi] Univ Michigan Hlth Syst, Div Cardiol, Ann Arbor, MI USA.
   [Austin, Melissa A.; Reiner, Alexander P.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
   [Logsdon, Benjamin A.; Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Biostat & Biomath, Seattle, WA 98104 USA.
   [Lettre, Guillaume] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.
   [Zonderman, Alan B.] NIA, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA.
   [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, NIH, Baltimore, MD 21224 USA.
   [Mohler, Emile R.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA.
   [Wilson, James G.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
RP Qayyum, R (reprint author), Johns Hopkins Sch Med, GeneSTAR Res Program, Div Gen Internal Med, Baltimore, MD USA.
EM rqayyum@jhmi.edu
RI Singleton, Andrew/C-3010-2009; Ziv, Elad/L-5396-2014; 
OI Qayyum, Rehan/0000-0003-3086-8014; Zonderman, Alan B/0000-0002-6523-4778
FU National Heart, Lung, and Blood Institute [HHSN268201100005C,
   HHSN268201100006C, HHSN268201100007C, HHSN268201100008C,
   HHSN268201100009C, HHSN268201100010C, HHSN268201100011C,
   HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694]; National Human
   Genome Research Institute [U01HG004402]; National Institutes of Health
   [HHSN268200625226C, HHSN268200782096C, R01 HL71862-06, 1K23HL105897-01];
   NIH Roadmap for Medical Research; NIH, National Institute on Aging;
   National Center on Minority Health and Health Disparities [Z01-AG000513,
   2009-149]; NIA [1R01AG032098-01A1]; National Heart, Lung, and Blood
   Institute (NHLBI) through the PROGENI consortia [U01 HL72518]; National
   Heart, Lung, and Blood Institute (NHLBI) through the STAMPEED consortia
   [R01 HL087698-01]; National Heart, Lung, and Blood Institute, National
   Institutes of Health, U.S. Department of Health and Human Services
   [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115,
   32118-32119, 32122, 42107-26, 42129-32, 44221]; Fondation de l'Institut
   de Cardiologie de Montreal; ARRA [N000949304]; NHGRI Genomics and
   Randomized Trials Network (GARNET) [U01 HG005152]; NIH Genes,
   Environment, and Health Initiative [GEI] [U01 HG004424]; GARNET
   Collaborative Research Group;  [UL1RR025005];  [N01-HC-48047]; 
   [N01-HC-95095];  [N01-HC-48048];  [N01-HC-48049];  [N01-HC-48050]; 
   [N01-HC-45204];  [N01-HC-45205];  [N01-HC-05187];  [N01-HC-45134]; 
   [N01-HC-95100];  [N01-HC-95170];  [N01-HC-95171];  [N01-HC-95172]
FX The ARIC, CARDIA, and JHS studies contributed data, ancillary study
   data, and DNA samples through the Broad Institute (N01-HC-65226) to
   create genotype/phenotype data base for wide dissemination to the
   biomedical research community. The Atherosclerosis Risk in Communities
   (ARIC) Study is carried out as a collaborative study supported by
   National Heart, Lung, and Blood Institute contracts (HHSN268201100005C,
   HHSN268201100006C, HHSN268201100007C, HHSN268201100008C,
   HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and
   HHSN268201100012C), R01HL087641, R01HL59367 and R01HL086694; National
   Human Genome Research Institute contract U01HG004402; and National
   Institutes of Health contract HHSN268200625226C. Infrastructure was
   partly supported by Grant Number UL1RR025005, a component of the
   National Institutes of Health and NIH Roadmap for Medical Research. The
   Coronary Artery Risk in Young Adults (CARDIA) was supported by grants to
   University of Alabama at Birmingham (N01-HC-48047, N01-HC-95095),
   University of Minnesota (N01-HC-48048), Northwestern University
   (N01-HC-48049), Kaiser Foundation Research Institute (N01-HC-48050),
   Tufts-New England Medical Center (N01-HC-45204), Wake Forest University
   (N01-HC-45205), Harbor-UCLA Research and Education Institute
   (N01-HC-05187), and University of California Irvine (N01-HC-45134,
   N01-HC-95100). The Jackson Heart Study (JHS) was supported by grants to
   Jackson State University (N01-HC-95170), University of Mississippi
   (N01-HC-95171), and Tougaloo College (N01-HC-95172). The Healthy Aging
   in Neighborhoods of Diversity across the Life Span Study (HANDLS) was
   supported by the Intramural Research Program of the NIH, National
   Institute on Aging and the National Center on Minority Health and Health
   Disparities (project # Z01-AG000513 and human subjects protocol #
   2009-149). Data analyses for the HANDLS study utilized the
   high-performance computational capabilities of the Biowulf Linux cluster
   at the National Institutes of Health, Bethesda, MD
   (http://biowulf.nih.gov). The Health ABC study was supported by NIA
   contracts N01AG62101, N01AG62103, and N01AG62106. The genome-wide
   association study was funded by NIA grant 1R01AG032098-01A1 to Wake
   Forest University Health Sciences and genotyping services were provided
   by the Center for Inherited Disease Research (CIDR). CIDR is fully
   funded through a federal contract from the National Institutes of Health
   to The Johns Hopkins University, contract number HHSN268200782096C. This
   research was supported in part by the Intramural Research Program of the
   NIH, National Institute on Aging. The GeneSTAR study was supported by
   the National Heart, Lung, and Blood Institute (NHLBI) through the
   PROGENI (U01 HL72518) and STAMPEED (R01 HL087698-01) consortia. The
   Women's Health Initiative (WHI) program is funded by the National Heart,
   Lung, and Blood Institute, National Institutes of Health, U.S.
   Department of Health and Human Services, through contracts N01WH22110,
   24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122,
   42107-26, 42129-32, and 44221. Additional support for this work was
   provided by the Fondation de l'Institut de Cardiologie de Montreal (to
   GL), and by NIH R01 HL71862-06 (to APR) NIH 1K23HL105897-01 (to RQ) and
   ARRA N000949304 (to APR). Funding support for WHI-GARNET was provided
   through the NHGRI Genomics and Randomized Trials Network (GARNET) (Grant
   Number U01 HG005152). Assistance with phenotype harmonization and
   genotype cleaning, as well as with general study coordination, was
   provided by the GARNET Coordinating Center (U01 HG005157).; Funding
   support for genotyping, which was performed at the Broad Institute of
   MIT and Harvard, was provided by the NIH Genes, Environment, and Health
   Initiative [GEI] (U01 HG004424). The funders had no role in study
   design, data collection and analysis, decision to publish, or
   preparation of the manuscript.; The authors wish to acknowledge the
   support of the National Heart, Lung, and Blood Institute and the
   contributions of the involved research institutions, study
   investigators, field staff, and study participants of Atherosclerosis
   Risk in Communities (ARIC), Coronary Artery Risk in Young Adults
   (CARDIA), Jackson Heart Study (JHS), and Broad Institute in creating the
   Candidate-gene Association Resource for biomedical research
   (CARe;http://public.nhlbi.nih.gov/GeneticsGenomics/home/care.aspx). The
   authors also wish to thank the investigators, staff, and participants of
   GeneSTAR, Health ABC, Healthy Aging in Neighborhoods of Diversity across
   the Life Span Study (HANDLS), and Women Health Initiative (WHI) for
   their important contributions. A listing of WHI investigators can be
   found at
   http://www.whiscience.org/publications/WHI_investigators_shortlist. pdf.
   The authors also wish to acknowledge the support of the GARNET
   Collaborative Research Group.
NR 65
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PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD MAR
PY 2012
VL 8
IS 3
AR e1002491
DI 10.1371/journal.pgen.1002491
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 918MV
UT WOS:000302254800002
PM 22423221
ER

PT J
AU Vattikuti, S
   Guo, J
   Chow, CC
AF Vattikuti, Shashaank
   Guo, Juen
   Chow, Carson C.
TI Heritability and Genetic Correlations Explained by Common SNPs for
   Metabolic Syndrome Traits
SO PLOS GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; BODY-MASS INDEX; PHENOTYPIC CORRELATIONS;
   FAMILIAL RESEMBLANCE; BLOOD-PRESSURE; HUMAN HEIGHT; LOCI; POPULATION;
   LIPIDS; IMPACT
AB We used a bivariate (multivariate) linear mixed-effects model to estimate the narrow-sense heritability (h(2)) and heritability explained by the common SNPs (h(g)(2)) for several metabolic syndrome (MetS) traits and the genetic correlation between pairs of traits for the Atherosclerosis Risk in Communities (ARIC) genome-wide association study (GWAS) population. MetS traits included body-mass index (BMI), waist-to-hip ratio (WHR), systolic blood pressure (SBP), fasting glucose (GLU), fasting insulin (INS), fasting trigylcerides (TG), and fasting high-density lipoprotein (HDL). We found the percentage of h(2) accounted for by common SNPs to be 58% of h(2) for height, 41% for BMI, 46% for WHR, 30% for GLU, 39% for INS, 34% for TG, 25% for HDL, and 80% for SBP. We confirmed prior reports for height and BMI using the ARIC population and independently in the Framingham Heart Study (FHS) population. We demonstrated that the multivariate model supported large genetic correlations between BMI and WHR and between TG and HDL. We also showed that the genetic correlations between the MetS traits are directly proportional to the phenotypic correlations.
C1 [Vattikuti, Shashaank; Guo, Juen; Chow, Carson C.] Natl Inst Diabet & Digest & Kidney Dis NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
RP Vattikuti, S (reprint author), Natl Inst Diabet & Digest & Kidney Dis NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
EM carsonc@mail.nih.gov
RI Chow, Carson/A-7970-2009
FU NIH/NIDDK; National Heart, Lung, and Blood Institute [N01-HC-55015,
   N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021,
   N01-HC-55022, R01HL087641, R01HL59367, R01HL086694]; National Human
   Genome Research Institute [U01HG004402]; National Institutes of Health
   [HHSN268200625226C]; National Institutes of Health and NIH Roadmap for
   Medical Research [UL1RR025005]; National Heart, Lung, and Blood
   Institute (NHLBI) in collaboration with Boston University [N01-HC-25195,
   N02-HL-64278]
FX This work was supported by the Intramural Research Program of the
   NIH/NIDDK. The Atherosclerosis Risk in Communities Study is carried out
   as a collaborative study supported by National Heart, Lung, and Blood
   Institute contracts N01-HC-55015, N01-HC-55016, N01-HC-55018,
   N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641,
   R01HL59367, and R01HL086694; National Human Genome Research Institute
   contract U01HG004402; and National Institutes of Health contract
   HHSN268200625226C. Infrastructure was partly supported by Grant Number
   UL1RR025005, a component of the National Institutes of Health and NIH
   Roadmap for Medical Research. The authors thank the staff and
   participants of the ARIC study for their important contributions. The
   Framingham Heart Study is conducted and supported by the National Heart,
   Lung, and Blood Institute (NHLBI) in collaboration with Boston
   University (Contract No. N01-HC-25195). This manuscript was not prepared
   in collaboration with investigators of the Framingham Heart Study and
   does not necessarily reflect the opinions or views of the Framingham
   Heart Study, Boston University, or NHLBI. Funding for SHARe genotyping
   was provided by NHLBI Contract N02-HL-64278. The funders had no role in
   study design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
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PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD MAR
PY 2012
VL 8
IS 3
AR e1002637
DI 10.1371/journal.pgen.1002637
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 918MV
UT WOS:000302254800093
PM 22479213
ER

PT J
AU Jefferson, WN
   Patisaul, HB
   Williams, CJ
AF Jefferson, Wendy N.
   Patisaul, Heather B.
   Williams, Carmen J.
TI Reproductive consequences of developmental phytoestrogen exposure
SO REPRODUCTION
LA English
DT Review
ID SEXUALLY DIMORPHIC NUCLEUS; SPRAGUE-DAWLEY RATS; SOY FORMULA MILK;
   NEONATAL EXPOSURE; FEMALE RATS; ISOFLAVONE PHYTOESTROGENS; UTERINE
   ADENOCARCINOMA; ENDOCRINE DISRUPTORS; ESTROGENIC ACTIVITY;
   ALPHA-FETOPROTEIN
AB Phytoestrogens, estrogenic compounds derived from plants, are ubiquitous in human and animal diets. These chemicals are generally much less potent than estradiol but act via similar mechanisms. The most common source of phytoestrogen exposure to humans is soybean-derived foods that are rich in the isoflavones genistein and daidzein. These isoflavones are also found at relatively high levels in soy-based infant formulas. Phytoestrogens have been promoted as healthy alternatives to synthetic estrogens and are found in many dietary supplements. The aim of this review is to examine the evidence that phytoestrogen exposure, particularly in the developmentally sensitive periods of life, has consequences for future reproductive health. Reproduction (2012) 143 247-260
C1 [Jefferson, Wendy N.; Williams, Carmen J.] NIEHS, Reprod Med Grp, Reprod & Dev Toxicol Lab, NIH,DHHS, Res Triangle Pk, NC 27709 USA.
   [Patisaul, Heather B.] N Carolina State Univ, Dept Biol, Raleigh, NC 27695 USA.
RP Williams, CJ (reprint author), NIEHS, Reprod Med Grp, Reprod & Dev Toxicol Lab, NIH,DHHS, POB 12233,MD E4-05, Res Triangle Pk, NC 27709 USA.
EM williamsc5@niehs.nih.gov
FU NIH, National Institutes of Environmental Health Sciences [Z01-ES102405,
   R01-ES016001]
FX This work was supported by the Intramural Research Program of the NIH,
   National Institutes of Environmental Health Sciences (Z01-ES102405, C J
   Williams) and by the NIH, National Institutes of Environmental Health
   Sciences (R01-ES016001, H B Patisaul).
NR 128
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U2 42
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
   ENGLAND
SN 1470-1626
J9 REPRODUCTION
JI Reproduction
PD MAR
PY 2012
VL 143
IS 3
BP 247
EP 260
DI 10.1530/REP-11-0369
PG 14
WC Developmental Biology; Reproductive Biology
SC Developmental Biology; Reproductive Biology
GA 927PR
UT WOS:000302920900002
PM 22223686
ER

PT J
AU Hill, MJ
   Levy, G
   Levens, ED
AF Hill, Micah J.
   Levy, Gary
   Levens, Eric D.
TI Does exogenous LH in ovarian stimulation improve assisted reproduction
   success? An appraisal of the literature
SO REPRODUCTIVE BIOMEDICINE ONLINE
LA English
DT Review
DE assisted reproductive technology; follicle-stimulating hormone; human
   chorionic gonadotrophin; human menopausal gonadotrophin; luteinizing
   hormone
ID IN-VITRO FERTILIZATION; HUMAN LUTEINIZING-HORMONE; HUMAN
   CHORIONIC-GONADOTROPIN; HUMAN MENOPAUSAL GONADOTROPIN; RECOMBINANT HUMAN
   FSH; INTRACYTOPLASMIC SPERM INJECTION; HIGHLY PURIFIED HMG; RANDOMIZED
   CONTROLLED-TRIAL; GNRH-ANTAGONIST PROTOCOL; OVULATION INDUCTION
AB A review of the scientific literature on the use of exogenous LH in assisted reproductive technology was performed by searching the MEDLINE, PubMed and Cochrane online databases. Scientific evidence was reviewed comparing recombinant FSH-only protocols to protocols supplemented with exogenous LH activity: human menopausal gonadotrophin (HMG), recombinant LH and mid-follicular human chorionic gonadotrophin (HCG). Studies were further compared based on pituitary suppression with gonadotrophin-releasing hormone (GnRH) antagonist and agonist protocols. Primary focus was given to randomized controlled trials and meta-analyses. Data from hypogonadotrophic hypogonadal patients demonstrated the importance of LH activity for success of assisted reproduction treatment. However, the majority of normogonadotrophic patients had adequate endogenous LH to successfully drive ovarian steroidogenesis and oocyte maturation. Exogenous LH supplementation was consistently associated with higher peak oestradiol concentrations. The use of HMG in long GnRH agonist cycles was associated with a 3-4% increase in live birth rate. There was insufficient evidence to make definitive conclusions on the need for exogenous LH activity in GnRH antagonist cycles or the benefit of recombinant LH and HCG protocols. Poor responders and patients 35 years of age and older may benefit from exogenous LH. (C) 2012, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
C1 [Hill, Micah J.; Levy, Gary; Levens, Eric D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
   [Levens, Eric D.] Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA.
RP Levens, ED (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
EM Eric.Levens@Integramed.com
FU NICHD, NIH, Bethesda, MD, USA
FX This work was supported in part by the Program in Reproductive and Adult
   Endocrinology, NICHD, NIH, Bethesda, MD, USA. The authors would like to
   thank Mary E Ryan, MLS, National Institutes of Health Library, Bethesda
   for her assistance in performing literature searches for this
   manuscript.
NR 85
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PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1472-6483
J9 REPROD BIOMED ONLINE
JI Reprod. Biomed. Online
PD MAR
PY 2012
VL 24
IS 3
BP 261
EP 271
DI 10.1016/j.rbmo.2011.12.005
PG 11
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 929FM
UT WOS:000303046700003
PM 22285265
ER

PT J
AU Singh, AK
   Seavey, CN
   Horvath, KA
   Mohiuddin, MM
AF Singh, Avneesh K.
   Seavey, Caleb N.
   Horvath, Keith A.
   Mohiuddin, Muhammad M.
TI Ex-vivo expanded baboon CD4+CD25Hi Treg cells suppress baboon anti-pig T
   and B cell immune response
SO XENOTRANSPLANTATION
LA English
DT Article
DE rapamycin; T regulatory cells; Treg; xenograft
ID REGULATORY CELLS; IN-VITRO; DENDRITIC CELLS; PERIPHERAL-BLOOD;
   EXPANSION; RAPAMYCIN; TRANSPLANTATION; INFLAMMATION; ACTIVATION;
   PHENOTYPE
AB Background: CD4(+) CD25(+) FoxP3(+) regulatory T (Treg) cells play an important role in regulating immune responses. A very small number of Treg cells are present in peripheral blood and lymphoid organs, but due to their ability to suppress the immune response, they have a high potential for immunotherapy in clinics. Successful ex-vivo expansion of naturally occurring CD4(+) CD25(+) T cells has been achieved after TCR stimulation in the presence of T cell growth factors. In this study, we evaluated the role of these Treg cells in suppressing proliferative response of baboon T and B cells to pig xenoantigens.
   Methods: Naturally occurring baboon CD4(+) CD25(+) regulatory T cells (nTreg) were sorted from peripheral blood and expanded in the presence of either anti-CD3/CD28 beads or irradiated pig peripheral blood mononuclear cells with IL-2. Treg cells were also enriched directly from CD4(+) T cells cultured in the presence of rapamycin (0.1-10 nm). Mixed lymphocyte culture and polyclonal B cell stimulation with ex-vivo Treg cells were performed to assess the function of ex-vivo expanded Treg cells.
   Results: The nTreg cells were expanded to more than 200-fold in 4 weeks and retained all the nTreg cell phenotypic characteristics, including high levels of FoxP3 expression. 2-fold increase in enrichment of CD4(+) CD25(+) FoxP3(+) Treg cells from CD4(+) cells was observed with rapamycin compared to cultures without rapamycin. The ex-vivo expanded Treg cells obtained from both methods were able to suppress the baboon anti-porcine xenogeneic T and B cell immune response in-vitro efficiently (more than 90% suppression at 1 : 1 ratio of T regulatory cells: T effector cells), and their suppression potential was retained even at 1 : 256 ratio. However, freshly isolated nTreg cells had only 70% suppression at 1 : 1 ratio, and their suppressive ability was reduced to <= 50% at 1 : 16 ratio. Furthermore, we have found that ex-vivo expanded Treg can also suppress the proliferation of B cells after polyclonal stimulation. Forty to 50 percent reduction in B cell proliferation was observed when ex-vivo expanded Treg cells were added to the culture at a 1 : 1 ratio. The addition of CD4(+) CD25 (Neg) cells however induced vigorous proliferation.
   Conclusion: Ex-vivo expanded CD4(+) CD25(+) FoxP3(+) Treg cells can be used to efficiently suppress xenogeneic immune responses by inhibiting T and B cell proliferation. These ex-vivo expanded Treg cells may also be used with other immunosuppressive agents to overcome xenograft rejection in preclinical xenotransplantation models.
C1 [Singh, Avneesh K.; Seavey, Caleb N.; Horvath, Keith A.; Mohiuddin, Muhammad M.] NHLBI, CSRP, NIH, Bethesda, MD 20892 USA.
RP Mohiuddin, MM (reprint author), NHLBI, CSRP, NIH, Rm B1D47G,MSC 1550,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA.
EM mohiuddinm@mail.nih.gov
RI Mohiuddin, Muhammad/M-4642-2013
OI Mohiuddin, Muhammad/0000-0003-4654-783X
NR 26
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U1 1
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0908-665X
J9 XENOTRANSPLANTATION
JI Xenotransplantation
PD MAR-APR
PY 2012
VL 19
IS 2
BP 102
EP 111
DI 10.1111/j.1399-3089.2012.00697.x
PG 10
WC Medicine, Research & Experimental; Transplantation
SC Research & Experimental Medicine; Transplantation
GA 925XT
UT WOS:000302796400005
PM 22497512
ER

PT J
AU Rao, M
AF Rao, Malla
TI The International Centers of Excellence for Malaria Research Foreward
SO ACTA TROPICA
LA English
DT Editorial Material
C1 NIAID, Div Microbiol & Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Rao, M (reprint author), NIAID, Div Microbiol & Infect Dis, NIH, Bethesda, MD 20892 USA.
EM MRao@niaid.nih.gov
NR 0
TC 7
Z9 7
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0001-706X
J9 ACTA TROP
JI Acta Trop.
PD MAR
PY 2012
VL 121
IS 3
SI SI
BP 157
EP 157
DI 10.1016/j.actatropica.2011.07.009
PG 1
WC Parasitology; Tropical Medicine
SC Parasitology; Tropical Medicine
GA 924CN
UT WOS:000302668500001
PM 21819955
ER

PT J
AU Ceesay, SJ
   Bojang, KA
   Nwakanma, D
   Conway, DJ
   Koita, OA
   Doumbia, SO
   Ndiaye, D
   Coulibaly, TF
   Diakite, M
   Traore, SF
   Coulibaly, M
   Ndiaye, JL
   Sarr, O
   Gaye, O
   Konate, L
   Sy, N
   Faye, B
   Faye, O
   Sogoba, N
   Jawara, M
   Dao, A
   Poudiougou, B
   Diawara, S
   Okebe, J
   Sangare, L
   Abubakar, I
   Sissako, A
   Diarra, A
   Keita, M
   Kandeh, B
   Long, CA
   Fairhurst, RM
   Duraisingh, M
   Perry, R
   Muskavitch, MAT
   Valim, C
   Volkman, SK
   Wirth, DF
   Krogstad, DJ
AF Ceesay, Serign J.
   Bojang, Kalifa A.
   Nwakanma, Davis
   Conway, David J.
   Koita, Ousmane A.
   Doumbia, Seydou O.
   Ndiaye, Daouda
   Coulibaly, Tinzana F.
   Diakite, Mahamadou
   Traore, Sekou F.
   Coulibaly, Mamadou
   Ndiaye, Jean-Louis
   Sarr, Ousmane
   Gaye, Oumar
   Konate, Lassana
   Sy, Ngayo
   Faye, Babacar
   Faye, Ousmane
   Sogoba, Nafomon
   Jawara, Musa
   Dao, Adama
   Poudiougou, Belco
   Diawara, Sory
   Okebe, Joseph
   Sangare, Lansana
   Abubakar, Ismaela
   Sissako, Aliou
   Diarra, Ayouba
   Keita, Moussa
   Kandeh, Balla
   Long, Carole A.
   Fairhurst, Rick M.
   Duraisingh, Manoj
   Perry, Robert
   Muskavitch, Marc A. T.
   Valim, Clarissa
   Volkman, Sarah K.
   Wirth, Dyann F.
   Krogstad, Donald J.
TI Sahel, savana, riverine and urban malaria in West Africa: Similar
   control policies with different outcomes
SO ACTA TROPICA
LA English
DT Article
DE Artemisinin Combination Therapies; Long-Lasting Insecticide Treated bed
   nets; Entomologic inoculation rate; Intermittent preventive treatment of
   malaria during pregnancy; Transmission intensity; Multiplicity of
   infection
ID PLASMODIUM-FALCIPARUM; ERADICATION; ELIMINATION; TRANSMISSION;
   FEASIBILITY; PROSPECTS; KENYA
AB The study sites for the West African ICEMR are in three countries (The Gambia, Senegal, Mali) and are located within 750 km of each other. In addition, the National Malaria Control Programmes of these countries have virtually identical policies: (1) Artemisinin Combination Therapies (ACTs) for the treatment of symptomatic Plasmodium falciparum infection, (2) Long-Lasting Insecticide-treated bed Nets (LLINs) to reduce the Entomololgic Inoculation Rate (EIR), and (3) sulfadoxine-pyrimethamine for the Intermittent Preventive Treatment of malaria during pregnancy (IPTp). However, the prevalence of P. falciparum malaria and the status of malaria control vary markedly across the four sites with differences in the duration of the transmission season (from 4-5 to 10-11 months), the intensity of transmission (with EIRs from unmeasurably low to 4-5 per person per month), multiplicity of infection (from a mean of 1.0 to means of 2-5) and the status of malaria control (from areas which have virtually no control to areas that are at the threshold of malaria elimination). The most important priority is the need to obtain comparable data on the population-based prevalence, incidence and transmission of malaria before new candidate interventions or combinations of interventions are introduced for malaria control. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Krogstad, Donald J.] Tulane Sch Publ Hlth & Trop Med, New Orleans, LA USA.
   [Ceesay, Serign J.; Bojang, Kalifa A.; Nwakanma, Davis; Conway, David J.; Jawara, Musa; Okebe, Joseph; Abubakar, Ismaela] MRC Labs, Int Ctr Excellence Malaria Res ICEMR W Africa, Fajara, Gambia.
   [Conway, David J.] London Sch Hyg & Trop Med, London WC1, England.
   [Koita, Ousmane A.; Doumbia, Seydou O.; Coulibaly, Tinzana F.; Diakite, Mahamadou; Traore, Sekou F.; Coulibaly, Mamadou; Sogoba, Nafomon; Dao, Adama; Poudiougou, Belco; Diawara, Sory; Sangare, Lansana; Sissako, Aliou; Diarra, Ayouba; Keita, Moussa] Uniivers Bamako, Bamako, Mali.
   [Ndiaye, Daouda; Ndiaye, Jean-Louis; Sarr, Ousmane; Gaye, Oumar; Konate, Lassana; Sy, Ngayo; Faye, Babacar; Faye, Ousmane] Uniivers Cheikh Anta Diop, Dakar, Senegal.
   [Long, Carole A.; Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
   [Duraisingh, Manoj; Valim, Clarissa; Volkman, Sarah K.; Wirth, Dyann F.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
   [Muskavitch, Marc A. T.] Boston Coll, Chestnut Hill, MA 02167 USA.
RP Krogstad, DJ (reprint author), Tulane Sch Publ Hlth & Trop Med, New Orleans, LA USA.
EM krogstad@tulane.edu
OI Conway, David/0000-0002-8711-3037
FU National Institutes of Allergy and Infectious Diseases (NIAID) [U19 AI
   089696]
FX The studies described here have been supported by a cooperative
   agreement from the National Institutes of Allergy and Infectious
   Diseases (NIAID U19 AI 089696) for an international center of excellence
   in malaria research (ICEMR) award to a consortium involving the
   University of Bamako in Mali, the University Cheikh Anta Diop in
   Senegal, the Medical Research Council (MRC) Laboratories in The Gambia,
   Harvard School of Public Health, Boston College, London School of
   Hygiene and Tropical Medicine and the Tulane School of Public Health and
   Tropical Medicine. We thank our many colleagues for administrative and
   financial support (Abdoulie Barry, Ron Cail, Salif Camara, Rosie Chavez,
   Abou Alassane Diallo, Khady Toure Diop, Ramona Gonski, Shannon Joyce,
   Dembo Kanteh, Glen McGugan, Carmen Mejia, Papa Alioune Ndao, Seybatou
   Magatte Ndaw, Peter Noble, Malla Rao, Brenda Rodriguez, Mamkumbah
   Sanneh, Moussa Dien Sarr, IP Singh, Paula Strickland, Don Van Noy, Joan
   Vivestomas, Tonu Wali, James Clint Welty, Kijuana Yarls), advice and
   mentoring (Tumani Corrah, Abarahmane Dia, Amadou Diallo, Souleymanne
   Mboup, Saliou Ndiaye, Omar Ndir), information technology and computing
   support (Christopher Whalen, Brian Moyer), public health and malaria
   control partnerships (Moussa Thior, Mrs. Adam Jagne Sonko, Claude-Emile
   Rwagacondo), and for generous access to their personal expertise
   (Jennifer Anderson, Thomas P. Eisele, Ivo Foppa, Nicholas Manoukis,
   Meredith McMorrow, David Parker, Robert Perry, Margaret Pinder, Jon Eric
   Tongren, Sixte Zigirumugabe).
NR 31
TC 8
Z9 8
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0001-706X
J9 ACTA TROP
JI Acta Trop.
PD MAR
PY 2012
VL 121
IS 3
SI SI
BP 166
EP 174
DI 10.1016/j.actatropica.2011.11.005
PG 9
WC Parasitology; Tropical Medicine
SC Parasitology; Tropical Medicine
GA 924CN
UT WOS:000302668500003
PM 22119584
ER

PT J
AU Doumbia, SO
   Ndiaye, D
   Koita, OA
   Diakite, M
   Nwakanma, D
   Coulibaly, M
   Traore, SF
   Keating, J
   Milner, DA
   Ndiaye, JL
   Sene, PD
   Ahouidi, A
   Dieye, TN
   Gaye, O
   Okebe, J
   Ceesay, SJ
   Ngwa, A
   Oriero, EC
   Konate, L
   Sy, N
   Jawara, M
   Faye, O
   Keita, M
   Cisse, M
   Sogoba, N
   Poudiougou, B
   Diawara, S
   Sangare, L
   Coulibaly, T
   Seck, I
   Abubakar, I
   Gomis, J
   Mather, FJ
   Sissako, A
   Diarra, A
   Kandeh, B
   Whalen, C
   Moyer, B
   Nnedu, O
   Thiero, O
   Bei, AK
   Daniels, R
   Miura, K
   Long, CA
   Fairhurst, RM
   Duraisingh, M
   Muskavitch, MAT
   D'Alessandro, U
   Conway, DJ
   Volkman, SK
   Valim, C
   Wirth, DF
   Krogstad, DJ
AF Doumbia, Seydou O.
   Ndiaye, Daouda
   Koita, Ousmane A.
   Diakite, Mahamadou
   Nwakanma, Davis
   Coulibaly, Mamadou
   Traore, Sekou F.
   Keating, Joseph
   Milner, Danny A., Jr.
   Ndiaye, Jean-Louis
   Sene, Papa Diogoye
   Ahouidi, Ambroise
   Dieye, Tandakha N.
   Gaye, Oumar
   Okebe, Joseph
   Ceesay, Serign J.
   Ngwa, Alfred
   Oriero, Eniyou C.
   Konate, Lassana
   Sy, Ngayo
   Jawara, Musa
   Faye, Ousmane
   Keita, Moussa
   Cisse, Moussa
   Sogoba, Nafomon
   Poudiougou, Belco
   Diawara, Sory
   Sangare, Lansana
   Coulibaly, Tinzana
   Seck, Ibrahima
   Abubakar, Ismaela
   Gomis, Jules
   Mather, Frances J.
   Sissako, Aliou
   Diarra, Ayouba
   Kandeh, Balla
   Whalen, Christopher
   Moyer, Brian
   Nnedu, Obinna
   Thiero, Oumar
   Bei, Amy K.
   Daniels, Rachel
   Miura, Kazutoyo
   Long, Carole A.
   Fairhurst, Rick M.
   Duraisingh, Manoj
   Muskavitch, Marc A. T.
   D'Alessandro, Umberto
   Conway, David J.
   Volkman, Sarah K.
   Valim, Clarissa
   Wirth, Dyann F.
   Krogstad, Donald J.
TI Improving malaria control in West Africa: Interruption of transmission
   as a paradigm shift
SO ACTA TROPICA
LA English
DT Article
DE Malaria control; Paradigm shift; Plasmodium falciparum; Population-based
   data
ID PLASMODIUM-FALCIPARUM MALARIA; SUB-SAHARAN AFRICA; ANOPHELES-GAMBIAE; P.
   FALCIPARUM; BURKINA-FASO; ERADICATION; EFFICACY; SAFETY; CYTOADHERENCE;
   ELIMINATION
AB With the paradigm shift from the reduction of morbidity and mortality to the interruption of transmission, the focus of malaria control broadens from symptomatic infections in children <= 5 years of age to include asymptomatic infections in older children and adults. In addition, as control efforts intensify and the number of interventions increases, there will be decreases in prevalence, incidence and transmission with additional decreases in morbidity and mortality. Expected secondary consequences of these changes include upward shifts in the peak ages for infection (parasitemia) and disease, increases in the ages for acquisition of antiparasite humoral and cellular immune responses and increases in false-negative blood smears and rapid diagnostic tests. Strategies to monitor these changes must include: (1) studies of the entire population (that are not restricted to children <= 5 or <= 10 years of age), (2) study sites in both cities and rural areas (because of increasing urbanization across sub-Saharan Africa) and (3) innovative strategies for surveillance as the prevalence of infection decreases and the frequency of false-negative smears and rapid diagnostic tests increases. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Keating, Joseph; Mather, Frances J.; Nnedu, Obinna; Krogstad, Donald J.] Tulane Sch Publ Hlth & Trop Med, New Orleans, LA USA.
   [Doumbia, Seydou O.; Koita, Ousmane A.; Diakite, Mahamadou; Coulibaly, Mamadou; Traore, Sekou F.; Keita, Moussa; Cisse, Moussa; Sogoba, Nafomon; Poudiougou, Belco; Diawara, Sory; Sangare, Lansana; Coulibaly, Tinzana; Sissako, Aliou; Diarra, Ayouba; Thiero, Oumar] Univ Bamako, Int Ctr Excellence Malaria Res W Africa, Bamako, Mali.
   [Ndiaye, Daouda; Ndiaye, Jean-Louis; Sene, Papa Diogoye; Ahouidi, Ambroise; Dieye, Tandakha N.; Gaye, Oumar; Konate, Lassana; Sy, Ngayo; Faye, Ousmane; Seck, Ibrahima; Gomis, Jules] Univ Cheikh Anta Diop, Dakar, Senegal.
   [Milner, Danny A., Jr.; Bei, Amy K.; Daniels, Rachel; Duraisingh, Manoj; Volkman, Sarah K.; Valim, Clarissa; Wirth, Dyann F.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
   [Whalen, Christopher; Moyer, Brian] Res Data, Washington, DC USA.
   [Miura, Kazutoyo; Long, Carole A.; Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
   [Muskavitch, Marc A. T.] Boston Coll, Chestnut Hill, MA 02167 USA.
   [Conway, David J.] London Sch Hyg & Trop Med, London WC1, England.
RP Krogstad, DJ (reprint author), Tulane Sch Publ Hlth & Trop Med, New Orleans, LA USA.
EM krogstad@tulane.edu
RI D'Alessandro, Umberto/D-3457-2015; 
OI D'Alessandro, Umberto/0000-0001-6341-5009; Conway,
   David/0000-0002-8711-3037
FU National Institutes of Allergy and Infectious Diseases (NIAID) [U19 AI
   089696]
FX The studies described and proposed here are supported by a cooperative
   agreement from the National Institutes of Allergy and Infectious
   Diseases (NIAID U19 AI 089696) for an International Center of Excellence
   in Malaria Research (ICEMR award) to a consortium involving the
   University of Bamako in Mali, the University Cheikh Anta Diop in
   Senegal, the Medical Research Council (MRC) Laboratories in The Gambia,
   Harvard School of Health; Boston College, London School of Hygiene and
   Tropical Medicine, the Laboratory of Malaria and Vector Research (NIAID)
   and the Tulane School of Public Health and Tropical Medicine. We thank
   our many colleagues for administrative and logistic support (Abdoulie
   Barry, Ron Cail, Salif Camara, Rosie Chavez, Abou Alassane Diallo, Khady
   Toure Diop, Ramona Gonski, Shannon Joyce, Dembo Kanteh, Denise
   Majnerick, Glen McGugan, Carmen Mejia, Papa Alioune Ndao, Seybatou
   Magatte Ndaw, Peter Noble, Malla Rao, Brenda Rodriguez, Mamkumbah
   Sanneh, Moussa Dieng Sarr, IP Singh, Paula Strickland, Don Van Noy, Joan
   Vivestomas, Tonu Wali, James Clint Welty, Kijuana Yarls), advice and
   mentoring (Tumani Corrah, Abdarahmane Dia, Amadou Diallo, Souleymanne
   Mboup, Saliou Nidaye, Omar Ndir), public health and malaria control
   partnerships (Moussa Thior, Mrs. Adam Jagne Sonko, Claude-Emile
   Rwagacondo) and for thoughtful discussions and access to their personal
   expertise (Jennifer Anderson, Thomas P. Eisele, Ivo Foppa, Nicholas
   Manoukis, Meredith McMorrow, David Parker, Robert Perry, Margaret
   Pinder, Jon Eric Tongren, Sixte Zigirumugabe).
NR 47
TC 7
Z9 7
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0001-706X
J9 ACTA TROP
JI Acta Trop.
PD MAR
PY 2012
VL 121
IS 3
SI SI
BP 175
EP 183
DI 10.1016/j.actatropica.2011.11.009
PG 9
WC Parasitology; Tropical Medicine
SC Parasitology; Tropical Medicine
GA 924CN
UT WOS:000302668500004
PM 22142790
ER

PT J
AU Cui, LW
   Yan, GY
   Sattabongkot, J
   Cao, YM
   Chen, B
   Chen, XG
   Fan, Q
   Fang, Q
   Jongwutiwes, S
   Parker, D
   Sirichaisinthop, J
   Kyaw, MP
   Su, XZ
   Yang, HL
   Yang, ZQ
   Wang, BM
   Xu, JW
   Zheng, B
   Zhong, DB
   Zhou, GF
AF Cui, Liwang
   Yan, Guiyun
   Sattabongkot, Jetsumon
   Cao, Yaming
   Chen, Bin
   Chen, Xiaoguang
   Fan, Qi
   Fang, Qiang
   Jongwutiwes, Somchai
   Parker, Daniel
   Sirichaisinthop, Jeeraphat
   Kyaw, Myat Phone
   Su, Xin-zhuan
   Yang, Henglin
   Yang, Zhaoqing
   Wang, Baomin
   Xu, Jianwei
   Zheng, Bin
   Zhong, Daibin
   Zhou, Guofa
TI Malaria in the Greater Mekong Subregion: Heterogeneity and complexity
SO ACTA TROPICA
LA English
DT Article
DE Malaria; The Greater Mekong Subregion; Epidemiology; Anopheles vectors;
   Drug resistance; Border malaria; Elimination
ID PLASMODIUM-FALCIPARUM MALARIA; ANTIMALARIAL-DRUG RESISTANCE; ISOTHERMAL
   AMPLIFICATION LAMP; POLYMERASE-CHAIN-REACTION; ANOPHELES-DIRUS COMPLEX;
   CROSS-SECTIONAL SURVEY; IMPREGNATED BED NETS; SOUTHEAST-ASIA;
   MOLECULAR-IDENTIFICATION; ARTESUNATE-MEFLOQUINE
AB The Greater Mekong Subregion (GMS), comprised of six countries including Cambodia, China's Yunnan Province, Lao PDR, Myanmar (Burma), Thailand and Vietnam, is one of the most threatening foci of malaria. Since the initiation of the WHO's Mekong Malaria Program a decade ago, malaria situation in the GMS has greatly improved, reflected in the continuous decline in annual malaria incidence and deaths. However, as many nations are moving towards malaria elimination, the GMS nations still face great challenges. Malaria epidemiology in this region exhibits enormous geographical heterogeneity with Myanmar and Cambodia remaining high-burden countries. Within each country, malaria distribution is also patchy, exemplified by 'border malaria' and 'forest malaria' with high transmission occurring along international borders and in forests or forest fringes, respectively. 'Border malaria' is extremely difficult to monitor, and frequent malaria introductions by migratory human populations constitute a major threat to neighboring, malaria-eliminating countries. Therefore, coordination between neighboring countries is essential for malaria elimination from the entire region. In addition to these operational difficulties, malaria control in the GMS also encounters several technological challenges. Contemporary malaria control measures rely heavily on effective chemotherapy and insecticide control of vector mosquitoes. However, the spread of multidrug resistance and potential emergence of artemisinin resistance in Plasmodium falciparum make resistance management a high priority in the GMS. This situation is further worsened by the circulation of counterfeit and substandard artemisinin-related drugs. In most endemic areas of the GMS, P. falciparum and Plasmodium vivax coexist, and in recent malaria control history, P. vivax has demonstrated remarkable resilience to control measures. Deployment of the only registered drug (primaquine) for the radical cure of vivax malaria is severely undermined due to high prevalence of glucose-6-phosphate dehydrogenase deficiency in target human populations. In the GMS, the dramatically different ecologies, diverse vector systems, and insecticide resistance render traditional mosquito control less efficient. Here we attempt to review the changing malaria epidemiology in the GMS, analyze the vector systems and patterns of malaria transmission, and identify the major challenges the malaria control community faces on its way to malaria elimination. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Cui, Liwang; Parker, Daniel] Penn State Univ, Dept Entomol, University Pk, PA 16801 USA.
   [Yan, Guiyun; Zhong, Daibin; Zhou, Guofa] Univ Calif Irvine, Program Publ Hlth, Irvine, CA 92697 USA.
   [Sattabongkot, Jetsumon] AFRIMS, Dept Entomol, Bangkok 10400, Thailand.
   [Cao, Yaming] China Med Univ, Coll Basic Med Sci, Dept Immunol, Shenyang, Peoples R China.
   [Cui, Liwang; Yan, Guiyun; Chen, Bin] Chongqing Normal Univ, Coll Life Sci, Chongqing 400047, Peoples R China.
   [Chen, Xiaoguang] So Med Univ, Sch Publ Hlth & Trop Med, Dept Etiobiol, Guangzhou 510515, Guangdong, Peoples R China.
   [Fan, Qi] Dalian Inst Biotechnol, Dalian 116024, Liaoning, Peoples R China.
   [Fang, Qiang] Bengbu Med Coll, Dept Microbiol & Parasitol, Bengbu 233030, Anhui, Peoples R China.
   [Jongwutiwes, Somchai] Chulalongkorn Univ, Fac Med, Dept Parasitol, Bangkok 10330, Thailand.
   [Sirichaisinthop, Jeeraphat] Vector Borne Dis Training Ctr, Sara Buri 18120, Thailand.
   [Kyaw, Myat Phone] Dept Med Res Lower Myanmar, Parasitol Res Div, Yangon 11191, Myanmar.
   [Su, Xin-zhuan] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
   [Yang, Henglin; Xu, Jianwei] Yunnan Inst Parasit Dis, Puer 665000, Yunnan, Peoples R China.
   [Yang, Zhaoqing] Kunming Med Univ, Dept Parasitol, Kunming 650031, Yunnan, Peoples R China.
   [Wang, Baomin] China Agr Univ, Coll Agron & Biotechnol, Beijing 100193, Peoples R China.
   [Zheng, Bin] Chinese Ctr Dis Control & Prevent, Natl Inst Parasit Dis, Shanghai 200025, Peoples R China.
RP Cui, LW (reprint author), Penn State Univ, Dept Entomol, 501 ASI Bldg, University Pk, PA 16801 USA.
EM luc2@psu.edu
RI Parker, Daniel/B-5471-2013; 
OI Parker, Daniel/0000-0002-5352-7338; Su, Xinzhuan/0000-0003-3246-3248
FU National Institute of Allergy and Infectious Diseases (NIAID), National
   Institutes of Health (NIH) [U19 AI089672]; Division of Intramural
   Research, NIAID, NIH
FX This work was supported by National Institute of Allergy and Infectious
   Diseases (NIAID), National Institutes of Health (NIH) (U19 AI089672) and
   partly by the Division of Intramural Research, NIAID, NIH.
NR 144
TC 84
Z9 86
U1 4
U2 51
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0001-706X
EI 1873-6254
J9 ACTA TROP
JI Acta Trop.
PD MAR
PY 2012
VL 121
IS 3
SI SI
BP 227
EP 239
DI 10.1016/j.actatropica.2011.02.016
PG 13
WC Parasitology; Tropical Medicine
SC Parasitology; Tropical Medicine
GA 924CN
UT WOS:000302668500011
PM 21382335
ER

PT J
AU Cui, LW
   Yan, GY
   Sattabongkot, J
   Chen, B
   Cao, YM
   Fan, Q
   Parker, D
   Sirichaisinthop, J
   Su, XZ
   Yang, HL
   Yang, ZQ
   Wang, BM
   Zhou, GF
AF Cui, Liwang
   Yan, Guiyun
   Sattabongkot, Jetsumon
   Chen, Bin
   Cao, Yaming
   Fan, Qi
   Parker, Daniel
   Sirichaisinthop, Jeeraphat
   Su, Xin-zhuan
   Yang, Henglin
   Yang, Zhaoqing
   Wang, Baomin
   Zhou, Guofa
TI Challenges and prospects for malaria elimination in the Greater Mekong
   Subregion
SO ACTA TROPICA
LA English
DT Article
DE Malaria; The Greater Mekong Subregion; Epidemiology; Vector systems;
   Drug resistance; Counterfeit drugs
ID PLASMODIUM-FALCIPARUM MALARIA; ARTEMISININ-RESISTANT MALARIA;
   ARTESUNATE-MEFLOQUINE; SOUTHEAST-ASIA; CAMBODIA; BORDER; ANTIMALARIALS;
   DEPLOYMENT; THAILAND; EFFICACY
AB Despite significant improvement in the malaria situation of the Greater Mekong Subregion (GMS), malaria control for the region continues to face a multitude of challenges. The extremely patchy malaria distribution, especially along international borders, makes disease surveillance and targeted control difficult. The vector systems are also diverse with dramatic differences in habitat ecology, biting behavior, and vectorial capacity, and there is a lack of effective transmission surveillance and control tools. Finally, in an era of heavy deployment of artemisinin-based combination therapies, the region acts as an epicenter of drug resistance, with the emergence of artemisinin resistant Plasmodium falciparum posing a threat to both regional and global malaria elimination campaigns. This problem is further exacerbated by the circulation of counterfeit and substandard artemisinin drugs. Accordingly, this Southeast Asian Malaria Research Center, consisting of a consortium of US and regional research institutions, has proposed four interlinked projects to address these most urgent problems in malaria control. The aims of these projects will help to substantially improve our understanding of malaria epidemiology, vector systems and their roles in malaria transmission, as well as the mechanisms of drug resistance in parasites. Through the training of next-generation scientists in malaria research, this program will help build up and strengthen regional research infrastructure and capacities, which are essential for sustained malaria control in this region. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Cui, Liwang; Parker, Daniel] Penn State Univ, Dept Entomol, University Pk, PA 16801 USA.
   [Yan, Guiyun; Zhou, Guofa] Univ Calif Irvine, Program Publ Hlth, Irvine, CA 92697 USA.
   [Sattabongkot, Jetsumon] AFRIMS, Dept Entomol, Bangkok 10400, Thailand.
   [Cui, Liwang; Yan, Guiyun; Chen, Bin] Chongqing Normal Univ, Coll Life Sci, Chongqing 400047, Peoples R China.
   [Cao, Yaming] China Med Univ, Dept Immunol, Coll Basic Med Sci, Shenyang, Peoples R China.
   [Fan, Qi] Dalian Inst Biotechnol, Dalian 116024, Liaoning Provin, Peoples R China.
   [Sirichaisinthop, Jeeraphat] Vector Borne Dis Training Ctr, Sara Buri 18120, Thailand.
   [Su, Xin-zhuan] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
   [Yang, Henglin] Yunnan Inst Parasit Dis, Puer 665000, Yunnan Province, Peoples R China.
   [Yang, Zhaoqing] Kunming Med Univ, Dept Parasitol, Kunming 650031, Yunnan, Peoples R China.
   [Wang, Baomin] China Agr Univ, Coll Agron Biotechnol, Beijing 100193, Peoples R China.
RP Cui, LW (reprint author), Penn State Univ, Dept Entomol, 501 ASI Bldg, University Pk, PA 16801 USA.
EM luc2@psu.edu
RI Parker, Daniel/B-5471-2013; 
OI Parker, Daniel/0000-0002-5352-7338; Su, Xinzhuan/0000-0003-3246-3248
FU National Institute of Allergy and Infectious Diseases, NIH [U19
   AI089672]; Division of Intramural Research, NIAID, NIH
FX This work was supported by National Institute of Allergy and Infectious
   Diseases, NIH (U19 AI089672). X. Su is supported by the Division of
   Intramural Research, NIAID, NIH.
NR 29
TC 24
Z9 25
U1 1
U2 15
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0001-706X
J9 ACTA TROP
JI Acta Trop.
PD MAR
PY 2012
VL 121
IS 3
SI SI
BP 240
EP 245
DI 10.1016/j.actatropica.2011.04.006
PG 6
WC Parasitology; Tropical Medicine
SC Parasitology; Tropical Medicine
GA 924CN
UT WOS:000302668500012
PM 21515238
ER

PT J
AU Herrera, S
   Quinones, ML
   Quintero, JP
   Corredor, V
   Fuller, DO
   Mateus, JC
   Calzada, JE
   Gutierrez, JB
   Llanos, A
   Soto, E
   Menendez, C
   Wu, YM
   Alonso, P
   Carrasquilla, G
   Galinski, M
   Beier, JC
   Arevalo-Herrera, M
AF Herrera, Socrates
   Lucia Quinones, Martha
   Pablo Quintero, Juan
   Corredor, Vladimir
   Fuller, Douglas O.
   Cesar Mateus, Julio
   Calzada, Jose E.
   Gutierrez, Juan B.
   Llanos, Alejandro
   Soto, Edison
   Menendez, Clara
   Wu, Yimin
   Alonso, Pedro
   Carrasquilla, Gabriel
   Galinski, Mary
   Beier, John C.
   Arevalo-Herrera, Myriam
TI Prospects for malaria elimination in non-Amazonian regions of Latin
   America
SO ACTA TROPICA
LA English
DT Article
DE Malaria; Plasmodium falciparum; Plasmodium vivax; Anopheles mosquitoes;
   Vector control; Epidemiology; Malaria elimination; Malaria pathogenesis;
   Non-Amazon regions; Latin America
ID PLASMODIUM-VIVAX MALARIA; ASYMPTOMATIC MALARIA; VACCINE DEVELOPMENT;
   ANOPHELES-DARLINGI; COLOMBIAN PACIFIC; FALCIPARUM; RESISTANCE; AREA;
   TRANSMISSION; POPULATION
AB Latin America contributes 1-1.2 million clinical malaria cases to the global malaria burden of about 300 million per year. In 21 malaria endemic countries, the population at risk in this region represents less than 10% of the total population exposed worldwide. Factors such as rapid deforestation, inadequate agricultural practices, climate change, political instability, and both increasing parasite drug resistance and vector resistance to insecticides contribute to malaria transmission. Recently, several malaria endemic countries have experienced a significant reduction in numbers of malaria cases. This is most likely due to actions taken by National Malaria Control Programs (NMCP) with the support from international funding agencies. We describe here the research strategies and activities to be undertaken by the Centro Latino Americano de Investigacion en Malaria (CLAIM), a new research center established for the non-Amazonian region of Latin America by the National Institute of Allergy and Infectious Diseases (NIAID). Throughout a network of countries in the region, initially including Colombia, Guatemala, Panama, and Peru. CLAIM will address major gaps in our understanding of changing malaria epidemiology, vector biology and control, and clinical malaria mainly due to Plasmodium vivax. In close partnership with NMCPs, CLAIM seeks to conduct research on how and why malaria is decreasing in many countries of the region as a basis for developing and implementing new strategies that will accelerate malaria elimination. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Herrera, Socrates; Pablo Quintero, Juan; Arevalo-Herrera, Myriam] Ctr Invest Cient Caucaseco, Cali 760042, Colombia.
   [Herrera, Socrates; Arevalo-Herrera, Myriam] Valle State Univ, Sch Hlth, Cali, Colombia.
   [Fuller, Douglas O.; Beier, John C.] Univ Miami, Coral Gables, FL 33124 USA.
   [Gutierrez, Juan B.] Ohio State Univ, Columbus, OH 43210 USA.
   [Llanos, Alejandro] Cayetano Heredia Univ, Lima, Peru.
   [Menendez, Clara; Alonso, Pedro] Univ Barcelona, Hosp Clin, Barcelona Ctr Int Hlth Res, E-08007 Barcelona, Spain.
   [Wu, Yimin] NIAD, Lab Malaria Immunol & Vaccinol, NIH, Bethesda, MD 20892 USA.
   [Galinski, Mary] Emory Univ Atlanta, Atlanta, GA USA.
RP Herrera, S (reprint author), Ctr Invest Cient Caucaseco, Cali 760042, Colombia.
EM sherrera@inmuno.org
OI Gutierrez, Juan B./0000-0002-0627-5035
FU US National Institute of Allergy and Infectious Diseases (NIAID/NIH)
   [U19AI089702]
FX This work has been supported by the US National Institute of Allergy and
   Infectious Diseases (NIAID/NIH) (Grant number U19AI089702).
NR 71
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U1 0
U2 15
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0001-706X
J9 ACTA TROP
JI Acta Trop.
PD MAR
PY 2012
VL 121
IS 3
SI SI
BP 315
EP 323
DI 10.1016/j.actatropica.2011.06.018
PG 9
WC Parasitology; Tropical Medicine
SC Parasitology; Tropical Medicine
GA 924CN
UT WOS:000302668500020
PM 21781953
ER

PT J
AU Okamoto, J
   Sakuma, KL
   Yan, H
   Qiu, PY
   Palmer, PH
   Johnson, CA
AF Okamoto, Janet
   Sakuma, Kari-Lyn
   Yan, He
   Qiu, Peiyuan
   Palmer, Paula H.
   Johnson, C. Anderson
TI A Qualitative Exploration of Youth in the "New" China: Perspectives on
   Tobacco Use From Adolescents in Southwest China
SO ASIA-PACIFIC JOURNAL OF PUBLIC HEALTH
LA English
DT Article
DE smoking; China; adolescent
ID SMOKING-BEHAVIOR; SCHOOL STUDENTS; ATTITUDES
AB School-based prevention programs are not common in China and the attempts to modify successful Western prevention programs have largely shown little effect. Distinct cultural and social systems differences could explain why modified programs have been unsuccessful. Smoking behavior is examined from the perspective of Chinese adolescents as part of the development of a large intervention trial. A total of 16 focus groups with 128 participants were conducted in Chengdu in Sichuan province of China. Impressions of adolescent smokers were mixed, most seeing the behavior as common among boys. Smokers were seen as being overwhelmed and stressed. Girls' smoking was mostly seen as universally "bad" and reflecting poorly on a girl's character. However, a small portion of focus group participants suggested that female smoking was fashionable and trendy. With social norms changing rapidly in the "new" China, understanding what the new generation of Chinese youth thinks about smoking is critical in determining how to address and tailor prevention efforts.
C1 [Okamoto, Janet] NCI, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
   [Sakuma, Kari-Lyn] Penn State Univ, State Coll, PA USA.
   [Yan, He] Chengdu Municipal Ctr Dis Control & Prevent, Chengdu, Peoples R China.
   [Qiu, Peiyuan] Sichuan Univ, Chengdu 610064, Peoples R China.
   [Palmer, Paula H.; Johnson, C. Anderson] Claremont Grad Univ, Claremont, CA USA.
RP Okamoto, J (reprint author), NCI, Behav Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,Room 4089B,MSC 7335, Bethesda, MD 20892 USA.
EM okamotojm@mail.nih.gov
OI Okamoto, Janet/0000-0002-3164-2183
FU Transdisciplinary Tobacco Use Research Center from the National Cancer
   Institute (NCI) [1 P50CA84735-01]; National Institute on Drug Abuse
   (NIDA); National Institute on Alcohol Abuse and Alcoholism (NIAAA)
FX This research was supported by Transdisciplinary Tobacco Use Research
   Center funding (grant number 1 P50CA84735-01) from the National Cancer
   Institute (NCI), National Institute on Drug Abuse (NIDA), and National
   Institute on Alcohol Abuse and Alcoholism (NIAAA).
NR 16
TC 1
Z9 1
U1 3
U2 6
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1010-5395
J9 ASIA-PAC J PUBLIC HE
JI Asia-Pac. J. Public Health
PD MAR
PY 2012
VL 24
IS 2
BP 296
EP 307
DI 10.1177/1010539510380735
PG 12
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 923AJ
UT WOS:000302590100007
PM 20829274
ER

PT J
AU Cho, YW
   Song, HJ
   Lee, JJ
   Lee, JH
   Lee, HJ
   Yi, SD
   Chang, HW
   Berl, MM
   Gaillard, WD
   Chang, Y
AF Cho, Yong Won
   Song, Hui-Jin
   Lee, Jae Jun
   Lee, Joo Hwa
   Lee, Hui Joong
   Yi, Sang Doe
   Chang, Hyuk Won
   Berl, Madison M.
   Gaillard, William D.
   Chang, Yongmin
TI Age-related differences in the brain areas outside the classical
   language areas among adults using category decision task
SO BRAIN AND LANGUAGE
LA English
DT Article
DE Language; fMRI; Laterality; Cognition
ID MEDIAL TEMPORAL-LOBE; VERBAL FLUENCY TASK; PREFRONTAL CORTEX; WADA TEST;
   SUBCORTICAL FUNCTIONS; WORD GENERATION; WORKING-MEMORY; FRONTAL-CORTEX;
   FUNCTIONAL MRI; FMRI
AB Older adults perform much like younger adults on language. This similar level of performance, however, may come about through different underlying brain processes. In the present study, we evaluated age-related differences in the brain areas outside the typical language areas among adults using a category decision task. Our results showed that similar activation patterns were found in classical language processing areas across the three age groups although regional lateralization indices in Broca's and Wernicke's areas decreased with age. The greatest differences, however, among the three groups were found primarily in the brain areas not associated with core language functioning including the hippocampus, middle frontal gyrus, ventromedial frontal cortex, medial superior parietal cortex and posterior cingulate cortex. Therefore, the non-classical language areas may exhibit an age-related difference between three age groups while the subjects show a similar activation pattern in the core, primary language processing during a semantic decision task. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Gaillard, William D.] George Washington Univ, Childrens Natl Med Ctr, Sch Med, Washington, DC 20010 USA.
   [Cho, Yong Won; Lee, Joo Hwa; Yi, Sang Doe] Keimyung Univ, Dongsan Med Ctr, Dept Neurol, Taegu, South Korea.
   [Lee, Hui Joong; Chang, Yongmin] Kyungpook Natl Univ & Hosp, Dept Med & Biol Engn, Taegu, South Korea.
   [Lee, Hui Joong; Chang, Yongmin] Kyungpook Natl Univ & Hosp, Dept Radiol, Taegu, South Korea.
   [Chang, Hyuk Won] Keimyung Univ, Dongsan Med Ctr, Dept Radiol, Taegu, South Korea.
   [Gaillard, William D.] NINDS, NIH, Bethesda, MD 20892 USA.
   [Chang, Yongmin] Kyungpook Natl Univ & Hosp, Dept Mol Med, Taegu, South Korea.
RP Gaillard, WD (reprint author), George Washington Univ, Childrens Natl Med Ctr, Sch Med, 111 Michigan Ave, Washington, DC 20010 USA.
EM wgaillar@cnmc.org; ychang@knu.ac.kr
FU Ministry of Health Welfare [A092106]; Keimyung University Dongsan
   Medical Center in KOREA
FX This work was supported by the Ministry of Health & Welfare (A092106)
   and a Research Promoting Grant from the Keimyung University Dongsan
   Medical Center in KOREA.
NR 47
TC 1
Z9 1
U1 8
U2 13
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0093-934X
J9 BRAIN LANG
JI Brain Lang.
PD MAR
PY 2012
VL 120
IS 3
BP 372
EP 380
DI 10.1016/j.bandl.2011.12.013
PG 9
WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences;
   Psychology, Experimental
SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences &
   Neurology; Psychology
GA 911XX
UT WOS:000301759100017
PM 22305968
ER

PT J
AU Stojilkovic, SS
AF Stojilkovic, Stanko S.
TI Molecular mechanisms of pituitary endocrine cell calcium handling
SO CELL CALCIUM
LA English
DT Article
DE Action potential; Calcium oscillations; cAMP; G protein-coupled
   receptors; IP3 receptor channels; Protein kinase A; Voltage-gated
   calcium channels
ID THYROTROPIN-RELEASING-HORMONE; VOLTAGE-GATED CA2+; IDENTIFIED RAT
   CORTICOTROPHS; SECRETING ADENOMA CELLS; CYTOSOLIC-FREE CALCIUM;
   RECTIFYING K+ CURRENT; PROTEIN-KINASE-A; ANTERIOR-PITUITARY;
   ACTION-POTENTIALS; FROG MELANOTROPHS
AB Endocrine pituitary cells express numerous voltage-gated Na+, Ca2+, K+, and Cl- channels and several ligand-gated channels, and they fire action potentials spontaneously. Depending on the cell type, this electrical activity can generate localized or global Ca2+ signals, the latter reaching the threshold for stimulus-secretion coupling. These cells also express numerous G-protein-coupled receptors, which can stimulate or silence electrical activity and Ca2+ influx through voltage-gated Ca2+ channels and hormone release. Receptors positively coupled to the adenylyl cyclase signaling pathway stimulate electrical activity with cAMP, which activates hyperpolarization-activated cyclic nucleotide-regulated channels directly, or by cAMP-dependent kinase-mediated phosphorylation of K+, Na+, Ca2+, and/or non-selective cation-conducting channels. Receptors that are negatively coupled to adenylyl cyclase signaling pathways inhibit spontaneous electrical activity and accompanied Ca2+ transients predominantly through the activation of inwardly rectifying K+ channels and the inhibition of voltage-gated Ca2+ channels. The Ca2+-mobilizing receptors activate inositol trisphosphate-gated Ca2+ channels in the endoplasmic reticulum, leading to Ca2+ release in an oscillatory or non-oscillatory manner, depending on the cell type. This Ca2+ release causes a cell type-specific modulation of electrical activity and intracellular Ca2+ handling. Published by Elsevier Ltd.
C1 NICHD, Sect Cellular Signaling, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
RP Stojilkovic, SS (reprint author), NICHD, Sect Cellular Signaling, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
EM stankos@helix.nih.gov
FU NIH, NICHD
FX SS is supported by an NIH grant from the Intramural Research Program of
   the NICHD, NIH. The author is thankful to Sir Michael J. Berridge for
   helpful discussions of calcium signaling in pituitary cells.
NR 107
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Z9 12
U1 0
U2 4
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 MAR-APR
PY 2012
VL 51
IS 3-4
SI SI
BP 212
EP 221
DI 10.1016/j.ceca.2011.11.003
PG 10
WC Cell Biology
SC Cell Biology
GA 920XV
UT WOS:000302443500002
PM 22138111
ER

PT J
AU Wehby, GL
   Murray, JC
   Wilcox, A
   Lie, RT
AF Wehby, George L.
   Murray, Jeffrey C.
   Wilcox, Allen
   Lie, Rolv T.
TI Smoking and body weight: Evidence using genetic instruments
SO ECONOMICS & HUMAN BIOLOGY
LA English
DT Article
DE Smoking; Obesity; Body mass index; Genetic instrumental variables;
   Quantile regression; Mendelian randomization
ID TRYPTOPHAN-HYDROXYLASE GENE; AMINOBUTYRIC-ACID RECEPTOR; NICOTINE
   DEPENDENCE; QUANTILE REGRESSION; ENVIRONMENTAL-INFLUENCES; MENDELIAN
   RANDOMIZATION; RISK-FACTOR; CIGARETTE-SMOKING; WEAK INSTRUMENTS;
   LUNG-CANCER
AB Several studies have evaluated whether the high and rising obesity rates over the past three decades may be due to the declining smoking rates. There is mixed evidence across studies - some find negative smoking effects and positive cigarette cost effects on body weight, while others find opposite effects. This study applies a unique approach to identify the smoking effects on body weight and to evaluate the heterogeneity in these effects across the body mass index (BMI) distribution by utilizing genetic instruments for smoking. Using a data sample of 1057 mothers from Norway, the study finds heterogeneous effects of cigarette smoking on BMI - smoking increases BMI at low/moderate BMI levels and decreases BMI at high BMI levels. The study highlights the potential advantages and challenges of employing genetic instrumental variables to identify behavior effects including the importance of qualifying the instruments and the need for large samples. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Wehby, George L.] Univ Iowa, Dept Hlth Management & Policy, Coll Publ Hlth, Iowa City, IA 52242 USA.
   [Murray, Jeffrey C.] Univ Iowa, Dept Pediat, Coll Med, Iowa City, IA 52242 USA.
   [Wilcox, Allen] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
   [Lie, Rolv T.] Univ Bergen, Bergen, Norway.
RP Wehby, GL (reprint author), Univ Iowa, Dept Hlth Management & Policy, Coll Publ Hlth, 200 Hawkins Dr,E205 GH, Iowa City, IA 52242 USA.
EM george-wehby@uiowa.edu
OI Wilcox, Allen/0000-0002-3376-1311
FU NIH/NIDCR [R03 DE018394, R01 DE20895]; NIH, National Institute of
   Environmental Health Sciences
FX Data analysis was supported in part by NIH/NIDCR grants R03 DE018394 and
   R01 DE20895. This research was supported in part by the Intramural
   Research Program of the NIH, National Institute of Environmental Health
   Sciences. The authors thank research seminar participants and Robert
   Wallace at the University of Iowa and Shin-Yi Chou at Lehigh University
   for helpful comments.
NR 86
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Z9 11
U1 4
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1570-677X
EI 1873-6130
J9 ECON HUM BIOL
JI Econ. Hum. Biol.
PD MAR
PY 2012
VL 10
IS 2
BP 113
EP 126
DI 10.1016/j.ehb.2011.09.002
PG 14
WC Economics; Public, Environmental & Occupational Health
SC Business & Economics; Public, Environmental & Occupational Health
GA 921ZI
UT WOS:000302516200001
PM 22024417
ER

PT J
AU Metenou, S
   Kovacs, M
   Dembele, B
   Coulibaly, YI
   Klion, AD
   Nutman, TB
AF Metenou, Simon
   Kovacs, Michael
   Dembele, Benoit
   Coulibaly, Yaya I.
   Klion, Amy D.
   Nutman, Thomas B.
TI Interferon regulatory factor modulation underlies the bystander
   suppression of malaria antigen-driven IL-12 and IFN-gamma in
   filaria-malaria co-infection
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
DE Cytokines; CXCR3 ligands; DCs; Interferon regulatory factors
ID HUMAN DENDRITIC CELLS; PLASMODIUM-FALCIPARUM MALARIA; NF-KAPPA-B;
   IMMUNE-RESPONSES; LYMPHATIC FILARIASIS; GENE-EXPRESSION; HELMINTH
   INFECTIONS; BRUGIA-MALAYI; FACTOR-I; T-CELLS
AB In areas where polyparasitism is highly prevalent, the impact of multiple parasites on the host response is underestimated. In particular, the presence of helminth infection coincident with malaria profoundly alters the production of malaria-specific IFN-?, IL-12p70, CXCL9, CXCL10 and CXCL11, cytokines/chemokines known to be critical in mediating malaria-specific immunity. In order to elucidate the mechanisms underlying the suppression of malaria-specific cytokines/chemokines, we assessed the expression of malaria-specific IL-12R beta 1, IL-12R beta 2 and interferon regulatory factor (IRF)-1 in blood obtained from 18 filaria-infected (Fil+) and 17 filaria-uninfected (Fil-) individuals in a filaria-malaria co-endemic region of Mali. We found that Fil+ individuals had significantly lower RNA expression of IRF-1 but not IL-12R beta 1 or IL-12R beta 2 in response to malaria antigen stimulation. We also measured the frequency of IL-12-producing DCs from these subjects and found that Fil+ subjects had lower frequencies of IL-12+ mDCs after malaria antigen stimulation than did the Fil- subjects. Modeling these data in vitro, we found that mDCs pre-exposed to live microfilariae not only produced significantly lower levels of CXCL-9, CXCL-10, IL-12p35, IL-12p40, IL-12p19 and CXCL-11 following stimulation with malaria antigen but also markedly downregulated the expression of IRF-1, IRF-2 and IRF-3 compared with microfilaria-unexposed mDCs. siRNA-inhibition of irf-1 in mDCs downregulated the production of IL-12p70 through repression of IL-12p35. Our data demonstrate that the modulation of IRFs seen in filarial (and presumably other tissue-invasive helminths) infection underlies the suppression of malaria-specific cytokines/chemokines that play a crucial role in immunity to malaria.
C1 [Metenou, Simon; Kovacs, Michael; Klion, Amy D.; Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD USA.
   [Dembele, Benoit; Coulibaly, Yaya I.] Univ Bamako, Filariasis Unit, Fac Med Pharm & Dent, Bamako, Mali.
RP Metenou, S (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD USA.
EM metenous@niaid.nih.gov
RI Metenou, Simon/C-1101-2013
FU Division of Intramural Research, National Institute of Allergy and
   Infectious Diseases, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
   Division of Intramural Research, National Institute of Allergy and
   Infectious Diseases, National Institutes of Health.
NR 49
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U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0014-2980
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD MAR
PY 2012
VL 42
IS 3
BP 641
EP 650
DI 10.1002/eji.201141991
PG 10
WC Immunology
SC Immunology
GA 922IT
UT WOS:000302541300012
PM 22213332
ER

PT J
AU Frick, KD
   Drye, LT
   Kempen, JH
   Dunn, JP
   Holland, GN
   Latkany, P
   Rao, NA
   Sen, HN
   Sugar, EA
   Thorne, JE
   Wang, RC
   Holbrook, JT
AF Frick, Kevin D.
   Drye, Lea T.
   Kempen, John H.
   Dunn, James P.
   Holland, Gary N.
   Latkany, Paul
   Rao, Narsing A.
   Sen, H. Nida
   Sugar, Elizabeth A.
   Thorne, Jennifer E.
   Wang, Robert C.
   Holbrook, Janet T.
CA Multictr Uveitis Steroid Treatment
TI Associations among Visual Acuity and Vision- and Health-Related Quality
   of Life among Patients in the Multicenter Uveitis Steroid Treatment
   Trial
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID FUNCTION QUESTIONNAIRE; STATES; EQ-5D; INTERMEDIATE; POPULATION;
   IMPAIRMENT; VALIDITY; UTILITY; SCORES
AB PURPOSE. To evaluate the associations between visual acuity and self-reported visual function; visual acuity and health-related quality of life (QoL) metrics; a summary measure of self-reported visual function and health-related QoL; and individual domains of self-reported visual function and health-related QoL in patients with uveitis.
   METHODS. Best-corrected visual acuity, vision-related functioning as assessed by the NEI VFQ-25, and health-related QoL as assessed by the SF-36 and EuroQoL EQ-5D questionnaires were obtained at enrollment in a clinical trial of uveitis treatments. Multivariate regression and Spearman correlations were used to evaluate associations between visual acuity, vision-related function, and health-related QoL.
   RESULTS. Among the 255 patients, median visual acuity in the better-seeing eyes was 20/25, the vision-related function score indicated impairment (median, 60), and health-related QoL scores were within the normal population range. Better visual acuity was predictive of higher visual function scores (P <= 0.001), a higher SF-36 physical component score, and a higher EQ-5D health utility score (P < 0.001). The vision-specific function score was predictive of all general health-related QoL (P < 0.001). The correlations between visual function score and general quality of life measures were moderate (p = 0.29-0.52).
   CONCLUSIONS. The vision-related function score correlated positively with visual acuity and moderately positively with general QoL measures. Cost-utility analyses relying on changes in generic healthy utility measures will be more likely to detect changes when there are clinically meaningful changes in vision-related function, rather than when there are only changes in visual acuity. (ClinicalTrials. gov number, NCT00132691.) (Invest Ophthalmol Vis Sci. 2012;53:1169-1176) DOI:10.1167/iovs.11-8259
C1 [Frick, Kevin D.] Johns Hopkins Univ, Dept Hlth Policy & Management, Bloomberg Sch Publ Hlth, Baltimore, MD 21218 USA.
   [Drye, Lea T.; Sugar, Elizabeth A.; Thorne, Jennifer E.; Holbrook, Janet T.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Ctr Clin Trials, Baltimore, MD USA.
   [Kempen, John H.] Univ Penn, Scheie Eye Inst, Dept Ophthalmol, Philadelphia, PA 19104 USA.
   [Kempen, John H.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
   [Kempen, John H.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
   [Kempen, John H.] Univ Penn, Dept Oncol, Philadelphia, PA 19104 USA.
   [Dunn, James P.; Thorne, Jennifer E.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Dept Ophthalmol, Baltimore, MD 21205 USA.
   [Holland, Gary N.] Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Dept Ophthalmol, Los Angeles, CA 90095 USA.
   [Latkany, Paul] New York Eye & Ear Inst, Dept Ophthalmol, New York, NY USA.
   [Rao, Narsing A.] USC Sch Med, Doheny Eye Inst, Dept Ophthalmol, Los Angeles, CA USA.
   [Sen, H. Nida] NEI, NIH, Bethesda, MD 20892 USA.
   [Sugar, Elizabeth A.] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA.
   [Sugar, Elizabeth A.] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA.
   [Wang, Robert C.] Texas Retina Associates, Dallas, TX USA.
RP Frick, KD (reprint author), 624 N Broadway,Room 606, Baltimore, MD 21205 USA.
EM kfrick@jhsph.edu
RI Taylor, Simon/C-1496-2008; 
OI Taylor, Simon/0000-0002-1228-881X; Drye, Lea/0000-0002-2964-1878
FU National Eye Institute [EYU10EY014655, EYU10EY014660, EY014656];
   Research to Prevent Blindness (RPB); Paul and Evanina Mackall
   Foundation; RPB James S. Adams Special Scholar Award; RPB Sybil
   Harrington Special Scholar Award
FX Supported by National Eye Institute Collaborative Grants EYU10EY014655,
   EYU10EY014660, and EY014656; Research to Prevent Blindness (RPB); and
   the Paul and Evanina Mackall Foundation. JHK was an RPB James S. Adams
   Special Scholar Award recipient during the time the study was conducted.
   JET is a recipient of the RPB Sybil Harrington Special Scholar Award.
   Bausch & Lomb provided support to the study in the form of donation of a
   limited number of fluocinolone acetonide implants for patients
   randomized to implant therapy who were uninsured or otherwise unable to
   pay for implants, but did not otherwise support the study. A
   representative of the National Eye Institute participated in the conduct
   of the study, including the study design and the collection, management,
   analysis, and interpretation of the data, as well as in the review and
   approval of the manuscript.
NR 31
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U1 1
U2 12
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD MAR
PY 2012
VL 53
IS 3
BP 1169
EP 1176
DI 10.1167/iovs.11-8259
PG 8
WC Ophthalmology
SC Ophthalmology
GA 925VT
UT WOS:000302790700013
PM 22247489
ER

PT J
AU Naeem, MA
   Chavali, VRM
   Ali, S
   Iqbal, M
   Riazuddin, S
   Khan, SN
   Husnain, T
   Sieving, PA
   Ayyagari, R
   Riazuddin, S
   Hejtmancik, JF
   Riazuddin, SA
AF Naeem, Muhammad Asif
   Chavali, Venkata R. M.
   Ali, Shahbaz
   Iqbal, Muhammad
   Riazuddin, Saima
   Khan, Shaheen N.
   Husnain, Tayyab
   Sieving, Paul A.
   Ayyagari, Radha
   Riazuddin, Sheikh
   Hejtmancik, J. Fielding
   Riazuddin, S. Amer
TI GNAT1 Associated with Autosomal Recessive Congenital Stationary Night
   Blindness
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID DOMINANT RETINITIS-PIGMENTOSA; ALPHA-TRANSDUCIN GNAT1; RHODOPSIN
   MUTATION; NONSENSE MUTATION; MISSENSE MUTATION; G-PROTEIN; GENE; ROD;
   CATARACT; SUBUNIT
AB PURPOSE. Congenital stationary night blindness is a nonprogressive retinal disorder manifesting as impaired night vision and is generally associated with other ocular symptoms, such as nystagmus, myopia, and strabismus. This study was conducted to further investigate the genetic basis of CSNB in a consanguineous Pakistani family.
   METHODS. A consanguineous family with multiple individuals manifesting cardinal symptoms of congenital stationary night blindness was ascertained. All family members underwent detailed ophthalmic examination, including fundus photographic examination and electroretinography. Blood samples were collected and genomic DNA was extracted. Exclusion and genome-wide linkage analyses were completed and two-point LOD scores were calculated. Bidirectional sequencing of GNAT1 was completed, and quantitative expression of Gnat1 transcript levels were investigated in ocular tissues at different postnatal intervals.
   RESULTS. The results of ophthalmic examinations were suggestive of early-onset stationary night blindness with no extraocular anomalies. The genome-wide scan localized the critical interval to chromosome 3, region p22.1-p14.3, with maximum two-point LOD scores of 3.09 at theta = 0, flanked by markers D3S3522 and D3S1289. Subsequently, a missense mutation in GNAT1, p. D129G, was identified, which segregated within the family, consistent with an autosomal recessive mode of inheritance, and was not present in 192 ethnically matched control chromosomes. Expression analysis suggested that Gnat1 is expressed at approximately postnatal day (P) 7 and is predominantly expressed in the retina.
   CONCLUSIONS. These data suggest that a homozygous missense mutation in GNAT1 is associated with autosomal recessive stationary night blindness. (Invest Ophthalmol Vis Sci. 2012;53:1353-1361) DOI:10.1167/iovs.11-8026
C1 [Riazuddin, S. Amer] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA.
   [Naeem, Muhammad Asif; Ali, Shahbaz; Iqbal, Muhammad; Riazuddin, Saima; Khan, Shaheen N.; Husnain, Tayyab; Riazuddin, Sheikh; Riazuddin, S. Amer] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan.
   [Chavali, Venkata R. M.; Ayyagari, Radha] Univ Calif San Diego, Shiley Eye Ctr, La Jolla, CA 92093 USA.
   [Riazuddin, Saima] Cincinnati Children Hosp Res Fdn, Div Pediat Otolaryngol Head & Neck Surg, Cincinnati, OH USA.
   [Riazuddin, Saima] Cincinnati Children Hosp Res Fdn, Div Ophthalmol, Cincinnati, OH USA.
   [Sieving, Paul A.; Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
   [Riazuddin, Sheikh] Univ Hlth Sci, Allama Iqbal Med Coll, Lahore, Pakistan.
RP Riazuddin, SA (reprint author), Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, 600 N Wolfe St,Maumenee 809A, Baltimore, MD 21287 USA.
EM riazuddin@ncemb.org
RI Nasim Khan, Shaheen/F-2135-2015; Husnain, Tayyab/G-3805-2015
FU Higher Education Commission (HEC); Ministry of Science and Technology,
   Islamabad, Pakistan; National Eye Institute [R01EY021237-01]
FX Supported in part by the Higher Education Commission (HEC) and the
   Ministry of Science and Technology, Islamabad, Pakistan, and by National
   Eye Institute Grant R01EY021237-01 (RA, SAR).
NR 39
TC 20
Z9 23
U1 0
U2 4
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD MAR
PY 2012
VL 53
IS 3
BP 1353
EP 1361
DI 10.1167/iovs.11-8026
PG 9
WC Ophthalmology
SC Ophthalmology
GA 925VT
UT WOS:000302790700038
PM 22190596
ER

PT J
AU Hou, X
   Hu, D
   Wang, YS
   Tang, ZS
   Zhang, F
   Chavakis, T
   Li, Y
   Li, XR
AF Hou, Xu
   Hu, Dan
   Wang, Yu-sheng
   Tang, Zhong-shu
   Zhang, Fan
   Chavakis, Triantafyllos
   Li, Yang
   Li, Xuri
TI Targeting of Junctional Adhesion Molecule-C Inhibits Experimental
   Choroidal Neovascularization
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; VASCULAR ENDOTHELIAL PERMEABILITY;
   PATHOLOGICAL ANGIOGENESIS; MACULAR DEGENERATION; JAM FAMILY; IN-VIVO;
   MACROPHAGE; EXPRESSION; PROTEINS; GROWTH
AB PURPOSE. To identify the expression of junctional adhesion molecule-C (JAM-C) in choroidal neovascularization (CNV) and evaluate the effect of JAM-C targeting on CNV formation and on cellular functions relevant to CNV in vitro, such as macrophage transmigration, human retinal pigment epithelial (hRPE) cell migration, and monolayer RPE permeability.
   METHODS. JAM-C expression in CNV was analyzed by real-time PCR, immunoblot analysis, and immunofluorescence staining. CNV area and blood vessel leakage were quantified using isolectin B4 staining and fluorescein angiography, respectively, 1 week after laser treatment. Macrophage infiltration within the CNV area was measured by immunofluorescence, and transmigration through monolayer RPE was analyzed using a transepithelial migration assay. After JAM-C shRNA transfection, human RPE cell migration was quantified using a transwell assay, and monolayer RPE permeability was determined by measuring the apical-to-basolateral movements of sodium fluorescein.
   RESULTS. JAM-C expression was upregulated during CNV formation after laser treatment in a time-dependent manner. However, no change in JAM-C expression was found in the retina up to 14 days after laser treatment. JAM-C targeting by intravitreal injection of JAM-C Fc chimera inhibited CNV, blood vessel leakage, and macrophage infiltration. JAM-C Fc chimera inhibited basolateral-to-apical transmigration in vitro through a monolayer of hRPE of macrophages from patients with wet AMD. In addition, shRNA-mediated JAM-C knockdown inhibited hRPE cell migration and hRPE permeability.
   CONCLUSIONS. JAM-C blockade may prove useful for CNV suppression by inhibiting macrophage transmigration, RPE cell migration, and monolayer RPE barrier malfunction. (Invest Ophthalmol Vis Sci. 2012;53:1584-1591) DOI:10.1167/iovs.11-9005
C1 [Hou, Xu; Hu, Dan; Wang, Yu-sheng] Fourth Mil Med Univ, Xijing Hosp, Eye Inst Chinese PLA, Dept Ophthalmol, Xian 710032, Shaanxi, Peoples R China.
   [Tang, Zhong-shu; Zhang, Fan; Li, Yang; Li, Xuri] NEI, NIH, Rockville, MD USA.
   [Chavakis, Triantafyllos] Univ Dresden, Dept Med, Div Vasc Inflammat Diabet & Kidney, Dresden, Germany.
   [Chavakis, Triantafyllos] Univ Dresden, Inst Physiol, Dresden, Germany.
RP Hu, D (reprint author), Fourth Mil Med Univ, Xijing Hosp, Eye Inst Chinese PLA, Dept Ophthalmol, Xian 710032, Shaanxi, Peoples R China.
EM hoodan@fmmu.edu.cn; wangys@fmmu.edu.cn
FU National Basic Research Program of China [973 Program/2011CB510200];
   National Natural Science Foundation of China [30872818, 81070748]
FX Supported by National Basic Research Program of China Grant 973
   Program/2011CB510200 and in part by National Natural Science Foundation
   of China Grants 30872818 and 81070748.
NR 33
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Z9 2
U1 1
U2 6
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD MAR
PY 2012
VL 53
IS 3
BP 1584
EP 1591
DI 10.1167/iovs.11-9005
PG 8
WC Ophthalmology
SC Ophthalmology
GA 925VT
UT WOS:000302790700067
PM 22323465
ER

PT J
AU Aschebrook-Kilfoy, B
   Zheng, TZ
   Foss, F
   Ma, SG
   Han, XS
   Lan, Q
   Holford, T
   Chen, YT
   Leaderer, B
   Rothman, N
   Zhang, YW
AF Aschebrook-Kilfoy, Briseis
   Zheng, Tongzhang
   Foss, Francine
   Ma, Shuangge
   Han, Xuesong
   Lan, Qing
   Holford, Theodore
   Chen, Yingtai
   Leaderer, Brian
   Rothman, Nathaniel
   Zhang, Yawei
TI Polymorphisms in immune function genes and non-Hodgkin lymphoma survival
SO JOURNAL OF CANCER SURVIVORSHIP-RESEARCH AND PRACTICE
LA English
DT Article
DE Non-Hodgkin lymphoma; Cytokines; Single nucleotide polymorphisms;
   Survival
ID UNITED-STATES; FOLLICULAR LYMPHOMA; INTERLEUKIN-6 GENE; SERUM-LEVELS; B
   CELLS; EXPRESSION; CANCER; CLASSIFICATION; PROGNOSIS; SUBTYPE
AB Introduction Cytokines play a critical role in regulating the immune system. In the tumor microenvironment, they influence survival, proliferation, differentiation, and movement of both tumor and stromal cells, and regulate tumor interactions with the extracellular matrix. Given these biologic properties, there is reason to hypothesize that cytokine activity influences the pathogenesis of non-Hodgkin lymphoma (NHL).
   Methods We investigated the effect of genetic variation in cytokine genes on NHL prognosis and survival by evaluating genetic variation in individual SNPs as well as the combined effect of multiple deleterious genotypes. Survival information from 496 female incident NHL cases diagnosed during 1996-2000 in Connecticut were abstracted from Connecticut Tumor Registry in 2008. Survival analyses were conducted by comparing Kaplan-Meier curves and hazard ratios (HR) were computed using Cox proportional hazard models adjusting for demographic and tumor characteristics for genes that were suggested by previous studies to be associated with NHL survival.
   Results We found that the variant IL6 genotype is significantly associated (HR=0.42; 95% CI: 0.23-0.77) with a decreased risk of death, as well as relapse and secondary cancer occurrence, among those with NHL. We also found that risk of death, relapse, and secondary cancers varied by specific SNPs for the follicular, DLBCL, and CLL/SLL histologic types. We identified combinations of polymorphisms whose combined deleterious effect significantly alter overall NHL survival and disease-free survival.
   Conclusion Our study provides evidence that the identification of genetic polymorphisms in cytokine genes may help improve the prediction of NHL survival and prognosis.
C1 [Aschebrook-Kilfoy, Briseis] NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, NIH,DHHS, Bethesda, MD 20892 USA.
   [Chen, Yingtai] Chinese Acad Med Sci, Canc Inst Hosp, Beijing 100730, Peoples R China.
   [Aschebrook-Kilfoy, Briseis; Zheng, Tongzhang; Ma, Shuangge; Han, Xuesong; Holford, Theodore; Leaderer, Brian; Zhang, Yawei] Yale Univ, Sch Publ Hlth, New Haven, CT USA.
   [Aschebrook-Kilfoy, Briseis; Lan, Qing; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Rockville, MD USA.
   [Foss, Francine] Yale Univ, Sch Med, Dept Med Oncol, New Haven, CT USA.
RP Aschebrook-Kilfoy, B (reprint author), NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, NIH,DHHS, 6120 Execut Blvd,EPS 8111, Bethesda, MD 20892 USA.
EM kilfoyb@mail.nih.gov
FU NIH/National Cancer Institute [NCI] [CA62006]; Yale Cancer Center
   [22067A]; National Institute of Health [NIH] [1D43TW008323-01,
   1D43TW007864-01]; CTSA from the National Center for Research Resources
   [NCRR], a component of the NIH and NHL roadmap for medical Research [UL1
   RR024139]
FX This research was supported in part by the Intramural Research Program
   of the NIH/National Cancer Institute [NCI], grant CA62006 from the NCI,
   by Hull Argall & Anna Grant 22067A from the Yale Cancer Center, and by
   Fogarty training grants 1D43TW008323-01 and 1D43TW007864-01 from the
   National Institute of Health [NIH]. This publication was made possible
   by CTSA Grant number UL1 RR024139 from the National Center for Research
   Resources [NCRR], a component of the NIH and NHL roadmap for medical
   Research. Its contents are solely the responsibility of the authors and
   do not necessarily represent the official view of NCRR. This research
   was approved by the DPH HIC. Certain data used in this study were
   obtained from the Connecticut Department of Public Health. The authors
   assume full responsibility for analyses and interpretation of these
   data.
NR 29
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Z9 7
U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1932-2259
J9 J CANCER SURVIV
JI J. Cancer Surviv.-Res. Pract.
PD MAR
PY 2012
VL 6
IS 1
BP 102
EP 114
DI 10.1007/s11764-010-0164-4
PG 13
WC Oncology; Social Sciences, Biomedical
SC Oncology; Biomedical Social Sciences
GA 920PS
UT WOS:000302419400012
PM 22113576
ER

PT J
AU Xu, H
   Cheng, C
   Devidas, M
   Pei, DQ
   Fan, YP
   Yang, WJ
   Neale, G
   Scheet, P
   Burchard, EG
   Torgerson, DG
   Eng, C
   Dean, M
   Antillon, F
   Winick, NJ
   Martin, PL
   Willman, CL
   Camitta, BM
   Reaman, GH
   Carroll, WL
   Loh, M
   Evans, WE
   Pui, CH
   Hunger, SP
   Relling, MV
   Yang, JJ
AF Xu, Heng
   Cheng, Cheng
   Devidas, Meenakshi
   Pei, Deqing
   Fan, Yiping
   Yang, Wenjian
   Neale, Geoff
   Scheet, Paul
   Burchard, Esteban G.
   Torgerson, Dara G.
   Eng, Celeste
   Dean, Michael
   Antillon, Frederico
   Winick, Naomi J.
   Martin, Paul L.
   Willman, Cheryl L.
   Camitta, Bruce M.
   Reaman, Gregory H.
   Carroll, William L.
   Loh, Mignon
   Evans, William E.
   Pui, Ching-Hon
   Hunger, Stephen P.
   Relling, Mary V.
   Yang, Jun J.
TI ARID5B Genetic Polymorphisms Contribute to Racial Disparities in the
   Incidence and Treatment Outcome of Childhood Acute Lymphoblastic
   Leukemia
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID ONCOLOGY-GROUP; RISK; POPULATIONS; CHILDREN; SURVIVAL; 10Q21.2; 7P12.2;
   RACE; SUSCEPTIBILITY; ASSOCIATION
AB Purpose
   Recent genome-wide screens have identified genetic variations in ARID5B associated with susceptibility to childhood acute lymphoblastic leukemia (ALL). We sought to determine the contribution of ARID5B single nucleotide polymorphisms (SNPs) to racial disparities in ALL susceptibility and treatment outcome.
   Patients and Methods
   We compared the association between ARID5B SNP genotype and ALL susceptibility in whites (> 95% European genetic ancestry; 978 cases and 1,046 controls) versus in Hispanics (> 10% Native American ancestry; 330 cases and 541 controls). We determined the relationships between ARID5B SNP genotype and ALL relapse risk in 1,605 children treated on the Children's Oncology Group (COG) P9904/9905 clinical trials.
   Results
   Among 49 ARID5B SNPs interrogated, 10 were significantly associated with ALL susceptibility in both whites and Hispanics (P < .05), with risk alleles consistently more frequent in Hispanics than in whites. rs10821936 exhibited the most significant association in both races (P = 8.4 x 10(-20) in whites; P = 1 x 10(-6) in Hispanics), and genotype at this SNP was highly correlated with local Native American genetic ancestry (P = 1.8 x 10(-8)). Multivariate analyses in Hispanics identified an additional SNP associated with ALL susceptibility independent of rs10821936. Eight ARID5B SNPs were associated with both ALL susceptibility and relapse hazard; the alleles related to higher ALL incidence were always linked to poorer treatment outcome and were more frequent in Hispanics.
   Conclusion
   ARID5B polymorphisms are important determinants of childhood ALL susceptibility and treatment outcome, and they contribute to racial disparities in this disease.
C1 [Yang, Jun J.] St Jude Childrens Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA.
   [Devidas, Meenakshi] Univ Florida, Gainesville, FL USA.
   [Scheet, Paul] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
   [Winick, Naomi J.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
   [Burchard, Esteban G.; Torgerson, Dara G.; Eng, Celeste; Loh, Mignon] Univ Calif San Francisco, San Francisco, CA 94143 USA.
   [Dean, Michael] NCI, Frederick, MD 21701 USA.
   [Antillon, Frederico] Unidad Nacl Oncol Pediat, Guatemala City, Guatemala.
   [Martin, Paul L.] Duke Univ, Durham, NC USA.
   [Willman, Cheryl L.] Univ New Mexico, Ctr Canc, Albuquerque, NM 87131 USA.
   [Camitta, Bruce M.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
   [Reaman, Gregory H.] George Washington Univ, Washington, DC USA.
   [Reaman, Gregory H.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
   [Carroll, William L.] NYU, Inst Canc, New York, NY USA.
   [Hunger, Stephen P.] Univ Colorado Denver, Sch Med, Aurora, CO USA.
   [Hunger, Stephen P.] Childrens Hosp, Aurora, CO USA.
RP Yang, JJ (reprint author), St Jude Childrens Hosp, Dept Pharmaceut Sci, 262 Danny Thomas Pl,MS 313, Memphis, TN 38105 USA.
EM jun.yang@stjude.org
RI Dean, Michael/G-8172-2012; Yang, Jun/B-6976-2008
OI Dean, Michael/0000-0003-2234-0631; Yang, Jun/0000-0002-0770-9659
FU National Institutes of Health, the National Cancer Institute [CA093552,
   CA78224, CA21765, R21CA158568, CA98543, RC4CA156449, CA114762, CA114766,
   CA021765-33, U10CA98413, U01GM61393, U01GM92666, HL088133]; American
   Lebanese Syrian Associated Charities, and CureSearch; American Society
   of Hematology Scholar Award; Alex Lemonade Stand Foundation; Sigma Tau
   Pharmaceuticals
FX Supported by Grants No. CA093552, CA78224, CA21765, R21CA158568,
   CA98543, RC4CA156449, CA114762, CA114766, CA021765-33, U10CA98413,
   U01GM61393, U01GM92666, and HL088133 from the National Institutes of
   Health, the National Cancer Institute Intramural Research Program, the
   American Lebanese Syrian Associated Charities, and CureSearch and by the
   American Society of Hematology Scholar Award and the Alex Lemonade Stand
   Foundation for Childhood Cancer Young Investigator Award (J.J.Y.).; Mary
   V. Relling, Sigma Tau Pharmaceuticals
NR 40
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U1 0
U2 11
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 MAR 1
PY 2012
VL 30
IS 7
BP 751
EP 757
DI 10.1200/JCO.2011.38.0345
PG 7
WC Oncology
SC Oncology
GA 923NG
UT WOS:000302625400018
PM 22291082
ER

PT J
AU Zhu, HT
   Ibrahim, JG
   Cho, H
   Tang, NS
AF Zhu, Hongtu
   Ibrahim, Joseph G.
   Cho, Hyunsoon
   Tang, Niansheng
TI Bayesian Case Influence Measures for Statistical Models With Missing
   Data
SO JOURNAL OF COMPUTATIONAL AND GRAPHICAL STATISTICS
LA English
DT Article
DE Case influence measures; Cook distance; First-order approximation;
   phi-divergence; Markov chain Monte Carlo
ID GENERALIZED LINEAR-MODELS; OUTLIER PROBLEMS; REGRESSION; DIAGNOSTICS;
   SENSITIVITY; DIVERGENCE; VIEW
AB We examine three Bayesian case influence measures including the phi-divergence, Cook's posterior mode distance, and Cook's posterior mean distance for identifying a set of influential observations for a variety of statistical models with missing data including models for longitudinal data and latent variable models in the absence/presence of missing data. Since it can be computationally prohibitive to compute these Bayesian case influence measures in models with missing data, we derive simple first-order approximations to the three Bayesian case influence measures by using the Laplace approximation formula and examine the applications of these approximations to the identification of influential sets. All of the computations for the first-order approximations can be easily done using Markov chain Monte Carlo samples from the posterior distribution based on the full data. Simulated data and an AIDS dataset are analyzed to illustrate the methodology. Supplemental materials for the article are available online.
C1 [Zhu, Hongtu; Ibrahim, Joseph G.; Cho, Hyunsoon] Univ N Carolina, Dept Biostat, NCI, Chapel Hill, NC 27599 USA.
   [Tang, Niansheng] Yunnan Univ, Dept Stat, Kunming, Peoples R China.
RP Zhu, HT (reprint author), Univ N Carolina, Dept Biostat, NCI, Chapel Hill, NC 27599 USA.
EM ibrahim@bios.unc.edu
OI Tang, Niansheng/0000-0001-7033-3845
FU NSF [SES-06-43663, BCS-08-26844]; NIH [UL1-RR025747-01, P01CA142538-01,
   AG033387, GM 70335, CA 74015]; NSFC [10561008, 1076104, 10961026]; NCET
   [NCET-07-0737]
FX We thank the editor, an associate editor, and a referee for many
   valuable suggestions. This work was supported in part by NSF
   SES-06-43663 and BCS-08-26844 and NIH grants UL1-RR025747-01,
   P01CA142538-01, and AG033387 to Dr. Zhu, NIH grants GM 70335,
   P01CA142538-01, and CA 74015 to Dr. Ibrahim, and NSFC grants 10561008,
   1076104, and 10961026 and NCET grant NCET-07-0737 to Dr. Tang.
NR 46
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U1 1
U2 3
PU AMER STATISTICAL ASSOC
PI ALEXANDRIA
PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA
SN 1061-8600
J9 J COMPUT GRAPH STAT
JI J. Comput. Graph. Stat.
PD MAR
PY 2012
VL 21
IS 1
BP 253
EP 271
DI 10.1198/jcgs.2011.10139
PG 19
WC Statistics & Probability
SC Mathematics
GA 922YP
UT WOS:000302585200015
PM 23399928
ER

PT J
AU Saldanha, LG
   Dwyer, JT
   Holden, JM
   Ireland, JD
   Andrews, KW
   Bailey, RL
   Gahche, JJ
   Hardy, CJ
   Moller, A
   Pilch, SM
   Roseland, JM
AF Saldanha, Leila G.
   Dwyer, Johanna T.
   Holden, Joanne M.
   Ireland, Jayne D.
   Andrews, Karen W.
   Bailey, Regan L.
   Gahche, Jaime J.
   Hardy, Constance J.
   Moller, Anders
   Pilch, Susan M.
   Roseland, Janet M.
TI A structured vocabulary for indexing dietary supplements in databases in
   the United States
SO JOURNAL OF FOOD COMPOSITION AND ANALYSIS
LA English
DT Article
DE LanguaL; Government; Dietary supplements; Databases; Indexing;
   Structured vocabulary; Thesaurus; Food analysis; Food composition
ID INTERNATIONAL INTERFACE STANDARD; FOOD DATABASES
AB Food composition databases are critical to assess and plan dietary intakes. Dietary supplement databases are also needed because dietary supplements make significant contributions to total nutrient intakes. However, no uniform system exists for classifying dietary supplement products and indexing their ingredients in such databases. Differing approaches to classifying these products make it difficult to retrieve or link information effectively. A consistent approach to classifying information within food composition databases led to the development of LanguaL (TM), a structured vocabulary. LanguaL (TM) is being adapted as an interface tool for classifying and retrieving product information in dietary supplement databases. This paper outlines proposed changes to the LanguaL (TM) thesaurus for indexing dietary supplement products and ingredients in databases. The choice of 12 of the original 14 LanguaL (TM) facets pertinent to dietary supplements, modifications to their scopes, and applications are described. The 12 chosen facets are: product type; product source; part of source; physical state, shape or form; ingredients; preservation method; packing medium; container or wrapping; contact surface; label claims/consumer group/dietary use; geographic places and regions; and adjunct characteristics of dietary supplements. Published by Elsevier Inc.
C1 [Saldanha, Leila G.; Dwyer, Johanna T.; Bailey, Regan L.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
   [Holden, Joanne M.; Andrews, Karen W.; Roseland, Janet M.] ARS, Nutrient Data Lab, USDA, Beltsville, MD 20705 USA.
   [Ireland, Jayne D.; Moller, Anders] Danish Food Informat, DK-4000 Roskilde, Denmark.
   [Gahche, Jaime J.] Natl Ctr Hlth Stat CDC, Natl Hlth & Nutr Examinat Survey Planning Branch, Hyattsville, MD 20782 USA.
   [Hardy, Constance J.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
   [Pilch, Susan M.] Natl Inst Hlth Lib, MEDLINE PubMed Database, Bethesda, MD 20892 USA.
RP Saldanha, LG (reprint author), NIH, Off Dietary Supplements, 6100 Execut Blvd MSC 7517,Room 3B01, Bethesda, MD 20892 USA.
EM saldanhl@mail.nih.gov
OI Dwyer, Johanna/0000-0002-0783-1769
FU Office of Dietary Supplements, National Institute of Health
FX The Office of Dietary Supplements, National Institute of Health funded
   the development of the LanguaL (TM) Dietary Supplement Structured
   Vocabulary for use in the United States.
NR 10
TC 4
Z9 4
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 0889-1575
J9 J FOOD COMPOS ANAL
JI J. Food Compos. Anal.
PD MAR
PY 2012
VL 25
IS 2
BP 226
EP 233
DI 10.1016/j.jfca.2011.10.003
PG 8
WC Chemistry, Applied; Food Science & Technology
SC Chemistry; Food Science & Technology
GA 920QX
UT WOS:000302423200017
PM 22611303
ER

PT J
AU Guler, AD
   Rainwater, A
   Parker, JG
   Jones, GL
   Argilli, E
   Arenkiel, BR
   Ehlers, MD
   Bonci, A
   Zweifel, LS
   Palmiter, RD
AF Gueler, Ali D.
   Rainwater, Aundrea
   Parker, Jones G.
   Jones, Graham L.
   Argilli, Emanuela
   Arenkiel, Benjamin R.
   Ehlers, Michael D.
   Bonci, Antonello
   Zweifel, Larry S.
   Palmiter, Richard D.
TI Transient activation of specific neurons in mice by selective expression
   of the capsaicin receptor
SO NATURE COMMUNICATIONS
LA English
DT Article
ID PROTEIN-COUPLED RECEPTORS; LONG-TERM DEPRESSION; REMOTE-CONTROL;
   SEROTONIN NEURONS; GENETIC APPROACH; NEURAL ACTIVITY; D-AMPHETAMINE;
   ION-CHANNEL; IN-VIVO; TRPV1
AB The ability to control the electrical activity of a neuronal subtype is a valuable tool in deciphering the role of discreet cell populations in complex neural circuits. Recent techniques that allow remote control of neurons are either labor intensive and invasive or indirectly coupled to neural electrical potential with low temporal resolution. Here we show the rapid, reversible and direct activation of genetically identified neuronal subpopulations by generating two inducible transgenic mouse models. Confined expression of the capsaicin receptor, TRPV1, allows cell-specific activation after peripheral or oral delivery of ligand in freely moving mice. Capsaicin-induced activation of dopaminergic or serotonergic neurons reversibly alters both physiological and behavioural responses within minutes, and lasts similar to 10 min. These models showcase a robust and remotely controllable genetic tool that modulates a distinct cell population without the need for invasive and labour-intensive approaches.
C1 [Gueler, Ali D.; Rainwater, Aundrea; Parker, Jones G.; Palmiter, Richard D.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
   [Gueler, Ali D.; Rainwater, Aundrea; Parker, Jones G.; Palmiter, Richard D.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
   [Jones, Graham L.; Zweifel, Larry S.] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA.
   [Jones, Graham L.; Zweifel, Larry S.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
   [Argilli, Emanuela; Bonci, Antonello] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94110 USA.
   [Arenkiel, Benjamin R.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
   [Ehlers, Michael D.] Pfizer Worldwide Res & Dev, Neurosci Res Unit, Groton, CT 06340 USA.
   [Bonci, Antonello] NIDA, Intramural Res Program, Baltimore, MD 21224 USA.
   [Bonci, Antonello] Johns Hopkins Univ, Sch Med, Solomon H Snyder Neurosci Inst, Baltimore, MD 21205 USA.
RP Palmiter, RD (reprint author), Univ Washington, Howard Hughes Med Inst, 1959 NE Pacific St,Box 357370, Seattle, WA 98195 USA.
EM palmiter@uw.edu
FU Klarman Family Foundation; HHMI; NIDA; NIMH [P30MH089887, R01MH086339];
   NARSAD; NIH [R00NS064171]
FX We thank Dr Xiaoxi Zhuang for the Slc6a3<SUP>Cre</SUP> mice; Dr Evan S.
   Deneris and Dr Michael Bruchas for ePet-Cre mice; Glenda Froelick for
   technical assistance; Nick Hollon for generating pilot FSCV data; Dr
   Albert Quintana for his expert assistance in microglia; Dr Michael J.
   Caterina, Dr Diane M. Durnam and Dr Jennifer L. Guler (also photo
   credit) for commenting on the manuscript and members of the Palmiter lab
   for helpful discussions during these studies. A. D. G. is a Howard
   Hughes Medical Institute (HHMI) Fellow of the Life Sciences Research
   Foundation. This work was supported by funding from Klarman Family
   Foundation (RDP); HHMI (RDP and MDE); NIDA intramural program (AB); NIMH
   (LSZ: P30MH089887; MDE: R01MH086339); NARSAD (BRA) and NIH (BRA:
   R00NS064171).
NR 51
TC 26
Z9 26
U1 0
U2 5
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 MAR
PY 2012
VL 3
AR 746
DI 10.1038/ncomms1749
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 923PB
UT WOS:000302630100035
PM 22434189
ER

PT J
AU Zhang, XT
   Liu, ZY
   Yi, J
   Tang, H
   Xing, JY
   Yu, MW
   Tong, TJ
   Shang, YF
   Gorospe, M
   Wang, WG
AF Zhang, Xiaotian
   Liu, Zhenyun
   Yi, Jie
   Tang, Hao
   Xing, Junyue
   Yu, Minqwei
   Tong, Tanjun
   Shang, Yongfeng
   Gorospe, Myriam
   Wang, Wengong
TI The tRNA methyltransferase NSun2 stabilizes p16(INK4) mRNA by
   methylating the 3 '-untranslated region of p16
SO NATURE COMMUNICATIONS
LA English
DT Article
ID BINDING PROTEIN HUR; 16S RIBOSOMAL-RNA; ESCHERICHIA-COLI; REPLICATIVE
   SENESCENCE; MISU NSUN2; TRANSLATION; EXPRESSION; INITIATION; RESIDUES;
   TARGET
AB The impact of methylation of the 3'-untranslated region (UTR) of a messenger RNA (mRNA) remains largely unknown. Here we show that NSun2, a transfer RNA methyltransferase, inhibits the turnover of p16(INK4) mRNA. Knockdown of NSun2 reduces p16 expression by shortening the half-life of the p16 mRNA, while overexpression of NSun2 stabilizes the p16 mRNA. In vitro methylation assays show that NSun2 methylates the p16 3'UTR at A988. Knockdown of NSun2 reduces the stability of the EGFP-p16 chimeric reporter transcripts bearing wild-type p16 3'UTR, but not p16 3'UTR with a mutant methylation site. Methylation by NSun2 prevents the association of p16 3'UTR with HuR, AUF1 and Ago2/RISC, and prevents the recruitment of EGFP-p16 3'UTR chimeric transcripts to processing bodies. In response to oxidative stress, NSun2 is essential for elevating p16 expression levels. We conclude that NSun2-mediated methylation of the p16 3'UTR is a novel mechanism to stabilize p16 mRNA.
C1 [Zhang, Xiaotian; Liu, Zhenyun; Yi, Jie; Tang, Hao; Xing, Junyue; Tong, Tanjun; Shang, Yongfeng; Wang, Wengong] Peking Univ, Dept Biochem & Mol Biol, Res Ctr Aging, Hlth Sci Ctr, Beijing 100191, Peoples R China.
   [Yu, Minqwei] Wuhan Univ, Clin Coll 1, Wuhan 430060, Peoples R China.
   [Gorospe, Myriam] NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA.
RP Wang, WG (reprint author), Peking Univ, Dept Biochem & Mol Biol, Res Ctr Aging, Hlth Sci Ctr, 38 Xueyuan Rd, Beijing 100191, Peoples R China.
EM wwg@bjmu.edu.cn
FU Major State Basic Research Development Program of China [2007CB507400];
   National Science Foundation of China [81070247, 30921062, 30973147];
   Ministry of Education of People's Republic of China [B07001]; National
   Institute on Aging-IRP, National Institutes of Health
FX This work was supported by Grant 2007CB507400 from the Major State Basic
   Research Development Program of China; Grants 81070247, 30921062 and
   30973147 from the National Science Foundation of China; and Grant B07001
   (111 project) from the Ministry of Education of People's Republic of
   China. M.G. was supported by the National Institute on Aging-IRP,
   National Institutes of Health.
NR 35
TC 36
Z9 41
U1 4
U2 19
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 MAR
PY 2012
VL 3
AR 712
DI 10.1038/ncomms1692
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 923PB
UT WOS:000302630100001
PM 22395603
ER

PT J
AU Troutman, SM
   Sissung, TM
   Cropp, CD
   Venzon, DJ
   Spencer, SD
   Adesunloye, BA
   Huang, X
   Karzai, FH
   Price, DK
   Figg, WD
AF Troutman, Sarah M.
   Sissung, Tristan M.
   Cropp, Cheryl D.
   Venzon, David J.
   Spencer, Shawn D.
   Adesunloye, Bamidele A.
   Huang, Xuan
   Karzai, Fatima H.
   Price, Douglas K.
   Figg, William D.
TI Racial Disparities in the Association Between Variants on 8q24 and
   Prostate Cancer: A Systematic Review and Meta-Analysis
SO ONCOLOGIST
LA English
DT Review
DE Prostatic neoplasms; Continental population groups; Single nucleotide
   polymorphisms; Meta-analysis; Risk assessment
ID GENOME-WIDE ASSOCIATION; LONG-RANGE INTERACTION; CHROMOSOME 8Q24; RISK
   LOCUS; CUMULATIVE ASSOCIATION; AFRICAN-AMERICANS; COMMON VARIANTS; MEN;
   SUSCEPTIBILITY; MYC
AB Recent studies implicate single nucleotide polymorphisms (SNPs) within the 8q24 region as a risk factor for prostate cancer (PCa). New developments suggest that 8q24 encodes regulators of the nearby MYC gene, a known oncogene. In order to better understand the implications of SNPs in this region, we performed meta-analyses, stratified by race, of seven SNPs and one microsatellite marker previously identified as risk loci on the 8q24 region of the genome. In addition, we reviewed the literature examining the possible associations between these polymorphisms and clinicopathological features of PCa. The results of the meta-analyses indicate that rs6983267, rs1447295, rs6983561, rs7837688, rs16901979, and DG8S737 are significantly associated with a higher risk for PCa for at least one race, whereas the variants rs13254738 and rs7000448 are not. The degree of association and frequency of the causative allele varied among men of different races. Though several studies have demonstrated an association between certain 8q24 SNPs and clinicopathological features of the disease, review of this topic revealed conflicting results. The Oncologist 2012; 17: 312-320
C1 [Troutman, Sarah M.; Price, Douglas K.; Figg, William D.] NCI, Mol Pharmacol Sect, Bethesda, MD 20892 USA.
   [Sissung, Tristan M.; Spencer, Shawn D.; Adesunloye, Bamidele A.; Huang, Xuan; Karzai, Fatima H.; Figg, William D.] NCI, Clin Pharmacol Program, Med Oncol Branch, Bethesda, MD 20892 USA.
   [Venzon, David J.] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA.
   [Cropp, Cheryl D.] NHGRI, Stat Genet Sect, Baltimore, MD USA.
RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, 9000 Rockville Pike,Bldg 10,Room 5A03, Bethesda, MD 20892 USA.
EM wdfigg@helix.nih.gov
RI Inov Farmaceutica, Inct/K-2313-2013; Figg Sr, William/M-2411-2016
NR 42
TC 11
Z9 12
U1 0
U2 2
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
J9 ONCOLOGIST
JI Oncologist
PD MAR
PY 2012
VL 17
IS 3
BP 312
EP 320
DI 10.1634/theoncologist.2011-0315
PG 9
WC Oncology
SC Oncology
GA 919YQ
UT WOS:000302368500003
PM 22382457
ER

PT J
AU Fox, E
   Patel, S
   Wathen, JK
   Schuetze, S
   Chawla, S
   Harmon, D
   Reinke, D
   Chugh, R
   Benjamin, RS
   Helman, LJ
AF Fox, Elizabeth
   Patel, Shreyaskumar
   Wathen, J. Kyle
   Schuetze, Scott
   Chawla, Sant
   Harmon, David
   Reinke, Denise
   Chugh, Rashmi
   Benjamin, Robert S.
   Helman, Lee J.
TI Phase II Study of Sequential Gemcitabine Followed by Docetaxel for
   Recurrent Ewing Sarcoma, Osteosarcoma, or Unresectable or Locally
   Recurrent Chondrosarcoma: Results of Sarcoma Alliance for Research
   Through Collaboration Study 003
SO ONCOLOGIST
LA English
DT Article
C1 [Fox, Elizabeth] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA.
   [Patel, Shreyaskumar; Wathen, J. Kyle; Benjamin, Robert S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
   [Schuetze, Scott; Reinke, Denise; Chugh, Rashmi] Univ Michigan, Ann Arbor, MI 48109 USA.
   [Chawla, Sant] Sarcoma Oncol Ctr, Los Angeles, CA USA.
   [Harmon, David] Massachusetts Gen Hosp, Boston, MA 02114 USA.
   [Fox, Elizabeth; Helman, Lee J.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Fox, E (reprint author), Childrens Hosp Philadelphia, Div Oncol, Civ Ctr Blvd,CTRB 4016, Philadelphia, PA 19104 USA.
EM foxe@email.chop.edu
NR 0
TC 31
Z9 34
U1 0
U2 3
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
J9 ONCOLOGIST
JI Oncologist
PD MAR
PY 2012
VL 17
IS 3
BP 321
EP 321
DI 10.1634/theoncologist.2010-0265
PG 1
WC Oncology
SC Oncology
GA 919YQ
UT WOS:000302368500004
PM 22363068
ER

PT J
AU Blum, AB
   Kleinman, LC
   Starfield, B
   Ross, JS
AF Blum, Alexander B.
   Kleinman, Lawrence C.
   Starfield, Barbara
   Ross, Joseph S.
TI Impact of State Laws That Extend Eligibility for Parents' Health
   Insurance Coverage to Young Adults
SO PEDIATRICS
LA English
DT Article
DE parental insurance; state laws; Affordable Care Act
AB BACKGROUND AND OBJECTIVES: The 2010 Affordable Care Act mandates that health insurance companies make those up to age 26 eligible for their parents' policies. Thirty-four states previously enacted similar laws. The authors sought to examine the impact on access to care of state laws extending eligibility of parents' insurance to young adults.
   METHODS: By using a difference-in-differences analysis, we examined the 2002-2004 and 2008-2009 Behavior Risk Factor Surveillance System to compare 3 states enacting laws in 2005 or 2006 with 17 states that have not enacted laws on 4 outcomes: self-reported health insurance coverage, identification of a personal physician/clinician, physical exam from a physician within the past 2 years, and forgoing care in the past year due to cost.
   RESULTS: For each outcome there was differential improvement among states enacting laws compared with states without laws. Health insurance differentially increased 0.2% (95% confidence interval [CI], -3.8% to 4.2%), from 67.6% to 68.1% pre-post in states enacting laws and from 68.5% to 68.7% in states without. Personal physician/clinician identification differentially increased 0.9% (95% CI -3.1% to 5.0%), from 62.4% to 65.5% in states enacting laws and from 58.0% to 60.2% in states without. Recent physical exams differentially increased significantly 4.6% (95% CI, 0%-9.2%), from 77.3% to 81.2% in states enacting laws and from 76.2% to 75.5% in states without. Forgone care due to cost differentially decreased significantly 3.9% (95% CI, -0.3% to -7.5%), from 20.4% to 18.2% in states enacting laws and from 17.8% to 19.4% in states without.
   CONCLUSIONS: States that expanded eligibility to parents' insurance in 2005 or 2006 experienced improvements in access to care among young adults. Pediatrics 2012; 129:426-432
C1 [Blum, Alexander B.; Kleinman, Lawrence C.] Mt Sinai Sch Med, Dept Hlth Evidence & Policy, New York, NY USA.
   [Blum, Alexander B.; Kleinman, Lawrence C.] Mt Sinai Sch Med, Dept Pediat, New York, NY USA.
   [Starfield, Barbara] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA.
   [Ross, Joseph S.] Yale Univ, Sch Med, Dept Med, Gen Internal Med Sect, New Haven, CT 06510 USA.
   [Ross, Joseph S.] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA.
RP Blum, AB (reprint author), NIH, Off Behav & Social Sci Res, Off Director, Bldg 31,Room B1C19,31 Ctr Dr, Bethesda, MD 20892 USA.
EM alex.blum@mountsinai.org
FU NCRR NIH HHS [UL1 RR029887]; NIA NIH HHS [K08AG032886, K08 AG032886];
   PHS HHS [T32HP10262]
NR 9
TC 5
Z9 5
U1 0
U2 8
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD MAR
PY 2012
VL 129
IS 3
BP 426
EP 432
DI 10.1542/peds.2011-1505
PG 7
WC Pediatrics
SC Pediatrics
GA 922IQ
UT WOS:000302541000038
PM 22331339
ER

PT J
AU Newman, J
   Bolton, EE
   Mueller-Dieckmann, J
   Fazio, VJ
   Gallagher, DT
   Lovell, D
   Luft, JR
   Peat, TS
   Ratcliffe, D
   Sayle, RA
   Snell, EH
   Taylor, K
   Vallotton, P
   Velanker, S
   von Delft, F
AF Newman, Janet
   Bolton, Evan E.
   Mueller-Dieckmann, Jochen
   Fazio, Vincent J.
   Gallagher, D. Travis
   Lovell, David
   Luft, Joseph R.
   Peat, Thomas S.
   Ratcliffe, David
   Sayle, Roger A.
   Snell, Edward H.
   Taylor, Kerry
   Vallotton, Pascal
   Velanker, Sameer
   von Delft, Frank
TI On the need for an international effort to capture, share and use
   crystallization screening data
SO ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION
   COMMUNICATIONS
LA English
DT Article
DE crystallization screening data; crystallization ontology
ID PROTEIN DATA-BANK; CRYSTALLOGRAPHIC INFORMATION FILE; STRUCTURAL
   GENOMICS; CRYSTAL; CLASSIFICATION; FEATURES; LESSONS; ARCHIVE
AB When crystallization screening is conducted many outcomes are observed but typically the only trial recorded in the literature is the condition that yielded the crystal(s) used for subsequent diffraction studies. The initial hit that was optimized and the results of all the other trials are lost. These missing results contain information that would be useful for an improved general understanding of crystallization. This paper provides a report of a crystallization data exchange (XDX) workshop organized by several international large-scale crystallization screening laboratories to discuss how this information may be captured and utilized. A group that administers a significant fraction of the world's crystallization screening results was convened, together with chemical and structural data informaticians and computational scientists who specialize in creating and analysing large disparate data sets. The development of a crystallization ontology for the crystallization community was proposed. This paper (by the attendees of the workshop) provides the thoughts and rationale leading to this conclusion. This is brought to the attention of the wider audience of crystallographers so that they are aware of these early efforts and can contribute to the process going forward.
C1 [Newman, Janet; Fazio, Vincent J.; Peat, Thomas S.] CSIRO, Parkville, Vic 3052, Australia.
   [Bolton, Evan E.] NIH, NCBI, NLM, Dept Hlth & Human Serv, Bethesda, MD 20894 USA.
   [Mueller-Dieckmann, Jochen] DESY, EMBL Hamburg Outstn, D-22603 Hamburg, Germany.
   [Gallagher, D. Travis] Natl Inst Stand & Technol, Rockville, MD 20850 USA.
   [Lovell, David; Ratcliffe, David; Taylor, Kerry] Australian Natl Univ, CSIRO ICT Ctr, Canberra, ACT 2601, Australia.
   [Lovell, David; Ratcliffe, David; Taylor, Kerry] Australian Natl Univ, CSIRO Math Informat & Stat, Canberra, ACT 2601, Australia.
   [Luft, Joseph R.; Snell, Edward H.] Hauptman Woodward Med Res Inst, Buffalo, NY 14203 USA.
   [Luft, Joseph R.; Snell, Edward H.] SUNY Buffalo, Dept Struct & Computat Biol, Buffalo, NY 14203 USA.
   [Sayle, Roger A.] NextMove Software, Innovat Ctr, Milton CB4 0EY, MA, England.
   [Vallotton, Pascal] Macquarie Univ Campus, CSIRO Math Informat & Stat N Ryde, N Ryde, NSW 1670, Australia.
   [Velanker, Sameer] European Bioinformat Inst, EMBL Outstn Hinxton, Cambridge CB10 1SD, England.
   [von Delft, Frank] Univ Oxford, Struct Genom Consortium, Oxford OX3 7DQ, England.
RP Newman, J (reprint author), CSIRO, 343 Royal Parade, Parkville, Vic 3052, Australia.
EM janet.newman@csiro.au
RI Lovell, David/A-4558-2009; Biology, Transformational/D-5787-2011;
   Newman, Janet/D-1857-2011; Vallotton, Pascal/A-3633-2009; Peat,
   Thomas/F-9817-2010; 
OI Lovell, David/0000-0002-3938-7586; Newman, Janet/0000-0003-2666-3219;
   Peat, Thomas/0000-0002-6488-0831; Sayle, Roger/0000-0003-0188-471X;
   Velankar, Sameer/0000-0002-8439-5964
FU NIGMS NIH HHS [R01 GM088396]
NR 35
TC 20
Z9 21
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1744-3091
J9 ACTA CRYSTALLOGR F
JI Acta Crystallogr. F-Struct. Biol. Cryst. Commun.
PD MAR
PY 2012
VL 68
BP 253
EP 258
DI 10.1107/S1744309112002618
PN 3
PG 6
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
   Biophysics; Crystallography
SC Biochemistry & Molecular Biology; Biophysics; Crystallography
GA 914AT
UT WOS:000301921300002
PM 22442216
ER

PT J
AU Novelli, EM
   Kato, GJ
   Ragni, MV
   Zhang, YZ
   Hildesheim, ME
   Nouraie, M
   Barge, S
   Meyer, MP
   Hassett, AC
   Gordeuk, VR
   Gladwin, MT
   Isenberg, JS
AF Novelli, Enrico M.
   Kato, Gregory J.
   Ragni, Margaret V.
   Zhang, Yingze
   Hildesheim, Mariana E.
   Nouraie, Mehdi
   Barge, Suchitra
   Meyer, Michael P.
   Hassett, Andrea Cortese
   Gordeuk, Victor R.
   Gladwin, Mark T.
   Isenberg, Jeffrey S.
TI Plasma thrombospondin-1 is increased during acute sickle cell
   vaso-occlusive events and associated with acute chest syndrome,
   hydroxyurea therapy, and lower hemolytic rates
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Article
ID PLATELET ACTIVATION; NITRIC-OXIDE; PULMONARY-HYPERTENSION; ERYTHROCYTE
   ADHERENCE; POTENTIAL ROLE; DISEASE; ENDOTHELIUM; INHIBITION; HEMOGLOBIN;
   RESPONSES
C1 [Novelli, Enrico M.] Univ Pittsburgh, VMI, UPMC, Div Hematol Oncol, Pittsburgh, PA USA.
   [Kato, Gregory J.] NHLBI, Sickle Cell Vasc Dis Sect, NIH, Bethesda, MD 20892 USA.
   [Ragni, Margaret V.] Hemophilia Ctr Western Penn, Pittsburgh, PA USA.
   [Zhang, Yingze; Hildesheim, Mariana E.; Barge, Suchitra; Gladwin, Mark T.; Isenberg, Jeffrey S.] Univ Pittsburgh, VMI, UPMC, Div Pulm, Pittsburgh, PA USA.
   [Nouraie, Mehdi; Gordeuk, Victor R.] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA.
   [Meyer, Michael P.; Hassett, Andrea Cortese] ITXM Diagnost, Pittsburgh, PA USA.
RP Isenberg, JS (reprint author), E1240 Biomed Sci Tower,200 Lothrop St, Pittsburgh, PA 15260 USA.
EM noveex@upmc.edu; jsi5@pitt.edu
RI Kato, Gregory/I-7615-2014
OI Kato, Gregory/0000-0003-4465-3217
FU Intramural NIH HHS [ZIA HL006162-01]; NCATS NIH HHS [UL1 TR000005]; NCI
   NIH HHS [K22 CA128616]; NHLBI NIH HHS [P01 HL103455, P01HL103455, R01
   HL-108954, R01 HL096973, R01 HL098032, R01 HL108954, R01HL096973,
   R01HL098032, ZIA HL005116]; PHS HHS [128767]
NR 25
TC 23
Z9 23
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0361-8609
J9 AM J HEMATOL
JI Am. J. Hematol.
PD MAR
PY 2012
VL 87
IS 3
BP 326
EP 330
DI 10.1002/ajh.22274
PG 5
WC Hematology
SC Hematology
GA 894TF
UT WOS:000300449100021
PM 22318901
ER

PT J
AU Goldsmith, JC
   Bonham, VL
   Joiner, CH
   Kato, GJ
   Noonan, AS
   Steinberg, MH
AF Goldsmith, Jonathan C.
   Bonham, Vence L.
   Joiner, Clinton H.
   Kato, Gregory J.
   Noonan, Allan S.
   Steinberg, Martin H.
TI Framing the research agenda for sickle cell trait: Building on the
   current understanding of clinical events and their potential
   implications
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Article
ID PLASMODIUM-FALCIPARUM MALARIA; INVASIVE PNEUMOCOCCAL DISEASE; RENAL
   MEDULLARY CARCINOMA; EXERTIONAL HEAT ILLNESS; HEMOGLOBIN-C TRAIT;
   RISK-FACTOR; 1ST-TRIMESTER VIABILITY; DIABETES-MELLITUS;
   ALPHA-THALASSEMIA; PREGNANT-WOMEN
C1 [Goldsmith, Jonathan C.] NHLBI, Blood Dis Branch, Div Blood Dis & Resources, NIH, Bethesda, MD 20892 USA.
   [Bonham, Vence L.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
   [Joiner, Clinton H.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA.
   [Kato, Gregory J.] NHLBI, Sickle Cell Vasc Dis Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA.
   [Noonan, Allan S.] Morgan State Univ, Sch Community Publ Hlth & Policy, Baltimore, MD 21239 USA.
   [Steinberg, Martin H.] Boston Univ, Sch Med, Boston, MA 02118 USA.
RP Goldsmith, JC (reprint author), 6701 Rockledge Dr,MSC 7950, Bethesda, MD 20892 USA.
EM goldsmithjc@nhlbi.nih.gov
RI Kato, Gregory/I-7615-2014; 
OI Kato, Gregory/0000-0003-4465-3217; Steinberg, Martin/0000-0001-8800-8020
FU Intramural NIH HHS [Z99 HL999999, ZIA HL006014-04]
NR 95
TC 34
Z9 37
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0361-8609
J9 AM J HEMATOL
JI Am. J. Hematol.
PD MAR
PY 2012
VL 87
IS 3
BP 340
EP 346
DI 10.1002/ajh.22271
PG 7
WC Hematology
SC Hematology
GA 894TF
UT WOS:000300449100028
PM 22307997
ER

PT J
AU Mohiuddin, MM
   Corcoran, PC
   Singh, AK
   Azimzadeh, A
   Hoyt, RF
   Thomas, ML
   Eckhaus, MA
   Seavey, C
   Ayares, D
   Pierson, RN
   Horvath, KA
AF Mohiuddin, M. M.
   Corcoran, P. C.
   Singh, A. K.
   Azimzadeh, A.
   Hoyt, R. F., Jr.
   Thomas, M. L.
   Eckhaus, M. A.
   Seavey, C.
   Ayares, D.
   Pierson, R. N., III
   Horvath, K. A.
TI B-Cell Depletion Extends the Survival of GTKO.hCD46Tg Pig Heart
   Xenografts in Baboons for up to 8 Months
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Article
DE anti-CD20; B-cell depletion; CD46 transgenic; complement; Gal knockout
   pigs; xenoantibody; Xenograft
ID GENE-KNOCKOUT PIGS; HYPERACUTE REJECTION; CLINICAL XENOTRANSPLANTATION;
   TRANSGENIC PIG; TRANSPLANTATION; PRIMATES; PROGRESS; MODEL
AB Xenotransplantation of genetically modified pig organs offers great potential to address the shortage of human organs for allotransplantation. Rejection in Gal knockout (GTKO) pigs due to elicited non-Gal antibody response required further genetic modifications of donor pigs and better control of the B-cell response to xenoantigens. We report significant prolongation of heterotopic alpha Galactosyl transferase knock-out and human CD46 transgenic (GTKO.hCD46Tg) pig cardiac xenografts survival in specific pathogen free baboons. Peritransplant B-cell depletion using 4 weekly doses of anti-CD20 antibody in the context of an established ATG, anti-CD154 and MMF-based immunosuppressive regimen prolonged GTKO.hCD46Tg graft survival for up to 236 days (n = 9, median survival 71 days and mean survival 94 days). B-cell depletion persisted for over 2 months, and elicited anti-non-Gal antibody production remained suppressed for the duration of graft follow-up. This result identifies a critical role for B cells in the mechanisms of elicited anti-non-Gal antibody and delayed xenograft rejection. Model-related morbidity due to variety of causes was seen in these experiments, suggesting that further therapeutic interventions, including candidate genetic modifications of donor pigs, may be necessary to reduce late morbidity in this model to a clinically manageable level.
C1 [Mohiuddin, M. M.; Corcoran, P. C.; Singh, A. K.; Seavey, C.; Horvath, K. A.] NHLBI, Cardiothorac Surg Res Program, NIH, Bethesda, MD 20892 USA.
   [Hoyt, R. F., Jr.] NHLBI, LAMS, NIH, Bethesda, MD 20892 USA.
   [Thomas, M. L.; Eckhaus, M. A.] NIH, DVR, ORS, Bethesda, MD 20892 USA.
   [Azimzadeh, A.; Pierson, R. N., III] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
   [Ayares, D.] Revivicor Inc, Blacksburg, VA USA.
RP Mohiuddin, MM (reprint author), NHLBI, Cardiothorac Surg Res Program, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM mohiuddinm@mail.nih.gov
RI Mohiuddin, Muhammad/M-4642-2013
OI Mohiuddin, Muhammad/0000-0003-4654-783X
FU NIAID NIH HHS [U01 AI066719, U19 AI090959]
NR 22
TC 53
Z9 55
U1 0
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1600-6135
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD MAR
PY 2012
VL 12
IS 3
BP 763
EP 771
DI 10.1111/j.1600-6143.2011.03846.x
PG 9
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 899QZ
UT WOS:000300832500033
PM 22070772
ER

PT J
AU Kontzias, A
   Chen, YQ
   Plass, N
   Garcia, D
   Joyal, E
   Wesley, R
   Goldbach-Mansky, RT
AF Kontzias, Apostolos
   Chen, Yongqing
   Plass, Nicole
   Garcia, Damaris
   Joyal, Elizabeth
   Wesley, Robert
   Goldbach-Mansky, Raphaela T.
TI COMPARATIVE CYTOKINE ANALYSIS ACROSS A SPECTRUM OF GENETICALLY AND/OR
   CLINICALLY DEFINED AUTO-INFLAMMATORY SYNDROMES
SO ANNALS OF THE RHEUMATIC DISEASES
LA English
DT Meeting Abstract
CT 32nd European Workshop for Rheumatology Research
CY FEB 23-25, 2012
CL Stockholm, SWEDEN
C1 [Kontzias, Apostolos; Chen, Yongqing; Plass, Nicole; Garcia, Damaris; Joyal, Elizabeth; Wesley, Robert; Goldbach-Mansky, Raphaela T.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0003-4967
J9 ANN RHEUM DIS
JI Ann. Rheum. Dis.
PD MAR
PY 2012
VL 71
SU 1
BP A82
EP A82
DI 10.1136/annrheumdis-2011-201238.23
PG 1
WC Rheumatology
SC Rheumatology
GA 919KF
UT WOS:000302323600189
ER

PT J
AU Oppenheimer, H
   Gabay, O
   Meir, H
   Haze, A
   Kandel, L
   Liebergall, M
   Gagarina, V
   Lee, EJ
   Dvir-Ginzberg, M
AF Oppenheimer, Hanna
   Gabay, Odile
   Meir, Hadar
   Haze, Amir
   Kandel, Leonid
   Liebergall, Meir
   Gagarina, Viktoria
   Lee, Eun Jin
   Dvir-Ginzberg, Mona
TI 75-kd sirtuin 1 blocks tumor necrosis factor a-mediated apoptosis in
   human osteoarthritic chondrocytes
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID FEMORAL-HEAD CARTILAGE; NF-KAPPA-B; CATHEPSIN-B; ENLARGED MITOCHONDRIA;
   RHEUMATOID-ARTHRITIS; CASPASE ACTIVATION; FACTOR-ALPHA; EXPRESSION;
   PROTEIN; CELLS
AB Objective Sirtuin 1 (SirT1) has been implicated in the regulation of human cartilage homeostasis and chondrocyte survival. Exposing human osteoarthritic (OA) chondrocytes to tumor necrosis factor a (TNFa) generates a stable and enzymatically inactive 75-kd form of SirT1 (75SirT1) via cathepsin Bmediated cleavage. Because 75SirT1 is resistant to further degradation, we hypothesized that it has a distinct role in OA, and the present study was undertaken to identify this role. Methods. The presence of cathepsin B and 75SirT in OA and normal human chondrocytes was analyzed. Confocal imaging of SirT1 was used to monitor its subcellular trafficking following TNF alpha stimulation. Co-immunofluorescence staining for cathepsin B, mitochondrial cytochrome oxidase subunit IV, and lysosome-associated membrane protein 1 together with SirT1 was performed. Human chondrocytes were tested for apoptosis by fluorescence-activated cell sorter analysis and immunoblotting for caspases 3 and 8. Human chondrocyte mitochondrial extracts were obtained and analyzed for 75SirT1-cytochrome c association. Results. Confocal imaging and immunoblot analyses following TNF alpha challenge of human chondrocytes demonstrated that 75SirT1 was exported to the cytoplasm and colocalized with the mitochondrial membrane. Consistent with this, immunoprecipitation and immunoblot analyses revealed that 75SirT1 is enriched in mitochondrial extracts and associates with cytochrome c following TNF alpha stimulation. Preventing nuclear export of 75SirT1 or reducing levels of full-length SirT1 and 75SirT1 augmented chondrocyte apoptosis in the presence of TNF alpha. Levels of cathepsin B and 75SirT1 were elevated in OA versus normal chondrocytes. Additional analyses showed that human chondrocytes exposed to OA-derived synovial fluid generated the 75SirT1 fragment. Conclusion. These data suggest that 75SirT1 promotes chondrocyte survival following exposure to proinflammatory cytokines.
C1 [Dvir-Ginzberg, Mona] Hebrew Univ Jerusalem, Fac Med Dent, Inst Dent Sci, Lab Cartilage Biol, IL-91120 Jerusalem, Israel.
   [Gabay, Odile; Gagarina, Viktoria; Lee, Eun Jin] NIAMSD, NIH, Bethesda, MD 20892 USA.
   [Haze, Amir; Kandel, Leonid; Liebergall, Meir] Hadassah Mt Scopus Hosp, Jerusalem, Israel.
RP Dvir-Ginzberg, M (reprint author), Hebrew Univ Jerusalem, Fac Med Dent, Inst Dent Sci, Lab Cartilage Biol, POB 12272, IL-91120 Jerusalem, Israel.
EM monad@ekmd.huji.ac.il
OI Dvir-Ginzberg, Mona/0000-0003-3089-6875
FU Marie Curie European International Reintegration Grant; National
   Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH
FX Supported by a Marie Curie European International Reintegration Grant
   award to Ms Oppenheimer and Ms Meir and by the Intramural Research
   Program of the National Institute of Arthritis and Musculoskeletal and
   Skin Diseases, NIH.
NR 51
TC 29
Z9 31
U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD MAR
PY 2012
VL 64
IS 3
BP 718
EP 728
DI 10.1002/art.33407
PG 11
WC Rheumatology
SC Rheumatology
GA 899SH
UT WOS:000300835900016
PM 21987377
ER

PT J
AU Ruuska, M
   Sahlberg, AS
   Colbert, RA
   Granfors, K
   Penttinen, MA
AF Ruuska, Marja
   Sahlberg, Anna S.
   Colbert, Robert A.
   Granfors, Kaisa
   Penttinen, Markus A.
TI Enhanced phosphorylation of STAT-1 is dependent on double-stranded
   RNA-dependent protein kinase signaling in HLA-B27-expressing U937
   monocytic cells
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID SALMONELLA-ENTERITIDIS; HLA-B27; ACTIVATION; PKR; INTERFERON; PATHWAYS;
   REQUIRES; TYROSINE
AB Objective To study the phosphorylation of STAT-1 in HLAB27transfected human monocytic cells and the role of the signaling molecules double-stranded RNAdependent protein kinase (PKR) and p38 in STAT-1 phosphorylation. Methods. U937 human monocytic cell transfectants stably expressing wild-type HLA-B27 or mutated HLA-B27 heavy chains with amino acid substitutions in the B pocket were prepared. Mock-transfected cells were prepared using the antibiotic resistance vectors (pSV2neo or RSV5neo) alone. Phorbol myristate acetate-differentiated cells were stimulated with lipopolysaccharide (LPS) or infected with Salmonella enteritidis. The phosphorylation and expression levels of STAT-1 protein were detected by Western blotting and flow cytometry. Specific inhibitors were added in cell culture to study the role of PKR and p38 in STAT-1 phosphorylation. Results. STAT-1 was constitutively highly phosphorylated on the tyrosine 701 residue in HLA-B27positive monocytic cells when compared to control cells, even prior to stimulation with LPS or bacteria. This phenotype was associated with the expression of HLAB27 heavy chains that misfold. In addition, phosphorylation of STAT-1 was dependent on PKR. Conclusion. Our results show that STAT-1 tyrosine 701 is constitutively highly phosphorylated in the HLA-B27-expressing monocyte/macrophage cell line. Since phosphorylation of tyrosine 701 on STAT-1 is sufficient to induce interferon (IFN)-dependent genes, constitutive activity of this phosphorylation site may lead to the overexpression of IFN-dependent genes, as well as other STAT-1-dependent genes, in HLA-B27 monocyte/ macrophages. Our results offer a mechanism by which B27 expression alone, without any external trigger, is potentially capable of inducing activation of STAT-1, a critical regulator of the inflammatory response.
C1 [Ruuska, Marja] Natl Inst Hlth & Welf, Dept Infect Dis Surveillance & Control, FIN-20520 Turku, Finland.
   [Colbert, Robert A.] NIAMSD, NIH, Bethesda, MD 20892 USA.
   [Penttinen, Markus A.] Univ Turku, Turku, Finland.
RP Ruuska, M (reprint author), Natl Inst Hlth & Welf, Dept Infect Dis Surveillance & Control, Kiinamyllynkatu 13, FIN-20520 Turku, Finland.
EM marja.ruuska@utu.fi
FU Academy of Finland; Sigrid Juselius Foundation; Finnish Cultural
   Foundation; NIH [R01-AR-46177, R01-AR-48372]
FX Supported by the Academy of Finland, the Sigrid Juselius Foundation, the
   Finnish Cultural Foundation, and the NIH (grants R01-AR-46177 and
   R01-AR-48372).
NR 16
TC 8
Z9 8
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD MAR
PY 2012
VL 64
IS 3
BP 772
EP 777
DI 10.1002/art.33391
PG 6
WC Rheumatology
SC Rheumatology
GA 899SH
UT WOS:000300835900021
PM 21968657
ER

PT J
AU Sneller, MC
   Hu, ZH
   Langford, CA
AF Sneller, Michael C.
   Hu, Zonghui
   Langford, Carol A.
TI A randomized controlled trial of rituximab following failure of
   antiviral therapy for hepatitis C virus-associated cryoglobulinemic
   vasculitis
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID II MIXED CRYOGLOBULINEMIA; LONG-TERM; INTERFERON-ALPHA; BIRMINGHAM
   VASCULITIS; ACTIVITY SCORE; HCV INFECTION; EFFICACY; ANTI-CD20;
   RIBAVIRIN; DISEASE
AB Objective To perform a randomized controlled trial of rituximab in patients with hepatitis C virus (HCV)associated mixed cryoglobulinemic vasculitis.
   Methods. We conducted a single-center, open-label, randomized controlled trial of rituximab (375 mg/m(2)/week for 4 weeks) compared to the best available therapy (maintenance or increase in immunosuppressive therapy) for HCV-associated cryoglobulinemic vasculitis in patients in whom antiviral therapy had failed to induce remission. The primary end point was disease remission at 6 months from study entry.
   Results. A total of 24 patients were enrolled (12 in each treatment group). Baseline disease activity and organ involvement were similar in the two groups. Ten patients in the rituximab group (83%) were in remission at study month 6, as compared with 1 patient in the control group (8%), a result that met the criterion for stopping the study (P < 0.001). The median duration of remission for rituximab-treated patients who reached the primary end point was 7 months. No adverse effects of rituximab on HCV plasma viremia or on hepatic transaminase levels were observed.
   Conclusion. Rituximab was a well-tolerated and effective treatment in patients with HCV-associated cryoglobulinemic vasculitis in whom antiviral therapy failed to induce remission.
C1 [Sneller, Michael C.] NIAID, Lab Immunoregulat, NIH, Bethesda, MD 20854 USA.
   [Langford, Carol A.] Cleveland Clin, Cleveland, OH 44106 USA.
RP Sneller, MC (reprint author), NIAID, Lab Immunoregulat, NIH, 10 Ctr Dr,MSC 1763, Bethesda, MD 20854 USA.
EM sneller@nih.gov
FU National Institute of Allergy and Infectious Diseases, NIH
FX Supported by the Intramural Research Program of the National Institute
   of Allergy and Infectious Diseases, NIH.
NR 25
TC 87
Z9 92
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD MAR
PY 2012
VL 64
IS 3
BP 835
EP 842
DI 10.1002/art.34322
PG 8
WC Rheumatology
SC Rheumatology
GA 899SH
UT WOS:000300835900028
PM 22147444
ER

PT J
AU Liu, Y
   Ramot, Y
   Torrelo, A
   Paller, AS
   Si, N
   Babay, S
   Kim, PW
   Sheikh, A
   Lee, CCR
   Chen, YQ
   Vera, A
   Zhang, X
   Goldbach-Mansky, R
   Zlotogorski, A
AF Liu, Yin
   Ramot, Yuval
   Torrelo, Antonio
   Paller, Amy S.
   Si, Nuo
   Babay, Sofia
   Kim, Peter W.
   Sheikh, Afzal
   Lee, Chyi-Chia Richard
   Chen, Yongqing
   Vera, Angel
   Zhang, Xue
   Goldbach-Mansky, Raphaela
   Zlotogorski, Abraham
TI Mutations in proteasome subunit ss type 8 cause chronic atypical
   neutrophilic dermatosis with lipodystrophy and elevated temperature with
   evidence of genetic and phenotypic heterogeneity
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID HYPER-GAMMA-GLOBULINEMIA; MUSCULAR-ATROPHY; AUTOINFLAMMATORY DISEASES;
   JOINT CONTRACTURES; MICROCYTIC ANEMIA; IMMUNOPROTEASOMES; PROTEINS;
   SURVIVAL
AB Objective Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE syndrome) is an autoinflammatory syndrome recently described in children. We undertook this study to investigate the clinical phenotype, genetic cause, and immune dysregulation in 9 CANDLE syndrome patients.
   Methods. Genomic DNA from all patients was screened for mutations in PSMB8 (proteasome subunit beta type 8). Cytokine levels were measured in sera from 3 patients. Skin biopsy samples were evaluated by immunohistochemistry, and blood microarray profile and STAT-1 phosphorylation were assessed in 4 patients and 3 patients, respectively.
   Results. One patient was homozygous for a novel nonsense mutation in PSMB8 (c.405C>A), suggesting a protein truncation; 4 patients were homozygous and 2 were heterozygous for a previously reported missense mutation (c.224C>T); and 1 patient showed no mutation. None of these sequence changes was observed in chromosomes from 750 healthy controls. Of the 4 patients with the same mutation, only 2 shared the same haplotype, indicating a mutational hot spot. PSMB8 mutation-positive and -negative patients expressed high levels of interferon-gamma (IFN gamma)-inducible protein 10. Levels of monocyte chemotactic protein 1, interleukin-6 (IL-6), and IL-1 receptor antagonist were moderately elevated. Microarray profiles and monocyte STAT-1 activation suggested a unique IFN signaling signature, unlike in other autoinflammatory disorders.
   Conclusion. CANDLE syndrome is caused by mutations in PSMB8, a gene recently reported to cause "JMP" syndrome (joint contractures, muscle atrophy, microcytic anemia, and panniculitis-induced childhood-onset lipodystrophy) in adults. We extend the clinical and pathogenic description of this novel autoinflammatory syndrome, thereby expanding the clinical and genetic disease spectrum of PSMB8-associated disorders. IFN may be a key mediator of the inflammatory response and may present a therapeutic target.
C1 [Zlotogorski, Abraham] Hadassah Hebrew Univ, Med Ctr, Dept Dermatol, IL-91120 Jerusalem, Israel.
   [Liu, Yin; Chen, Yongqing; Goldbach-Mansky, Raphaela] NIAMSD, NIH, Bethesda, MD 20892 USA.
   [Torrelo, Antonio] Hosp Nino Jesus, Madrid, Spain.
   [Paller, Amy S.] Northwestern Univ, Chicago, IL 60611 USA.
   [Si, Nuo] Chinese Acad Med Sci, Beijing 100730, Peoples R China.
   [Si, Nuo] Peking Union Med Coll, Beijing 100021, Peoples R China.
   [Kim, Peter W.; Sheikh, Afzal] NHGRI, NIH, Bethesda, MD 20892 USA.
   [Lee, Chyi-Chia Richard] NCI, NIH, Bethesda, MD 20892 USA.
   [Vera, Angel] Hosp Carlos Haya, Malaga, Spain.
RP Zlotogorski, A (reprint author), Hadassah Hebrew Univ, Med Ctr, Dept Dermatol, POB 12000, IL-91120 Jerusalem, Israel.
EM goldbacr@mail.nih.gov; zloto@cc.huji.ac.il
RI Lee, Chyi-Chia/I-1938-2013
OI Lee, Chyi-Chia/0000-0002-5306-7781
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases,
   NIH; Authority for Research and Development, Hebrew University of
   Jerusalem; Novartis; Biovitrum; Regeneron; Hadassah Medical Center
FX Supported by the Intramural Research Program of the National Institute
   of Arthritis and Musculoskeletal and Skin Diseases, NIH, and by the
   Authority for Research and Development, Hebrew University of Jerusalem
   (to Dr. Zlotogorski). Dr. Ramot is recipient of a Hadassah Medical
   Center Young Clinician Award.; Dr. Goldbach-Mansky has received grant
   support for studies from Novartis, Biovitrum, and Regeneron.
NR 27
TC 102
Z9 105
U1 2
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD MAR
PY 2012
VL 64
IS 3
BP 895
EP 907
DI 10.1002/art.33368
PG 13
WC Rheumatology
SC Rheumatology
GA 899SH
UT WOS:000300835900034
PM 21953331
ER

PT J
AU Bulua, AC
   Mogul, DB
   Aksentijevich, I
   Singh, H
   He, DY
   Muenz, LR
   Ward, MM
   Yarboro, CH
   Kastner, DL
   Siegel, RM
   Hull, KM
AF Bulua, Ariel C.
   Mogul, Douglas B.
   Aksentijevich, Ivona
   Singh, Harjot
   He, David Y.
   Muenz, Larry R.
   Ward, Michael M.
   Yarboro, Cheryl H.
   Kastner, Daniel L.
   Siegel, Richard M.
   Hull, Keith M.
TI Efficacy of etanercept in the tumor necrosis factor receptor-associated
   periodic syndrome: A prospective, open-label, dose-escalation study
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID SYNDROME TRAPS; TNF-RECEPTOR; FUSION PROTEIN; ANAKINRA
AB Objective To investigate the efficacy of etanercept in improving the symptoms and underlying inflammation in patients with tumor necrosis factor receptorassociated periodic syndrome (TRAPS).
   Methods. Fifteen patients with TRAPS were enrolled in a prospective, open-label, dose-escalation study. Patients recorded attacks, symptom severity, and use of ancillary medications in a daily diary. Blood samples were collected during each period and measured for levels of acute-phase reactants. Between 7 years and 9 years after the conclusion of the initial study, patients completed a followup survey and were evaluated to determine the long-term outcome of etanercept treatment.
   Results. Etanercept treatment significantly attenuated the total symptom score and reduced the frequency of symptoms. Etanercept also reduced levels of acute-phase reactants, particularly during asymptomatic periods. During a 10-year followup period, patients continued to receive etanercept for a median of 3.3 years, with a number of patients switching to anti-interleukin-1 beta receptor therapy or not receiving biologic agents, most frequently citing injection site reactions and lack of efficacy as reasons for discontinuation. However, patients continuing to receive etanercept had reduced symptoms at followup.
   Conclusion. Etanercept reduces symptoms and serum levels of inflammatory markers of TRAPS in a dose-dependent manner, but does not completely normalize symptoms or acute-phase reactant levels. Although long-term adherence to etanercept is poor, continuing to receive etanercept may provide continued symptomatic benefit.
C1 [Bulua, Ariel C.; Mogul, Douglas B.; Aksentijevich, Ivona; Singh, Harjot; Ward, Michael M.; Yarboro, Cheryl H.; Kastner, Daniel L.; Siegel, Richard M.; Hull, Keith M.] NIAMSD, NIH, Bethesda, MD 20892 USA.
   [He, David Y.; Muenz, Larry R.] Larry R Muenz & Associates, Gaithersburg, MD USA.
RP Siegel, RM (reprint author), NIAMSD, NIH, Bldg 10,Room 13C103, Bethesda, MD 20892 USA.
EM rsiegel@nih.gov
FU NIH; National Institute of Allergy and Infectious Diseases
FX Drs. Bulua, Mogul, and Singh's work was supported by the NIH Clinical
   Research Training Program, a public-private partnership between the NIH
   and Pfizer.; We would like to thank the clinical staff of the National
   Institute of Arthritis and Musculoskeletal and Skin Diseases,
   particularly Jane Dean, Anne Jones, Beverly Barham, and Dr. Amanda
   Ombrello; and Dr. Karyl Barron (National Institute of Allergy and
   Infectious Diseases), for excellent patient care and research support.
NR 15
TC 48
Z9 51
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD MAR
PY 2012
VL 64
IS 3
BP 908
EP 913
DI 10.1002/art.33416
PG 6
WC Rheumatology
SC Rheumatology
GA 899SH
UT WOS:000300835900035
PM 22006113
ER

PT J
AU Roschewski, M
   Wilson, WH
AF Roschewski, Mark
   Wilson, Wyndham H.
TI EBV-associated lymphomas in adults
SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY
LA English
DT Article
DE LMP-1; EBNA-1; Epstein-Barr virus; lymphoma; lymphoproliferative
   disorders; cytotoxic T-lymphocyte
ID EPSTEIN-BARR-VIRUS; T-CELL LYMPHOMA; POSTTRANSPLANT LYMPHOPROLIFERATIVE
   DISORDERS; PYOTHORAX-ASSOCIATED LYMPHOMA; PRIMARY EFFUSION LYMPHOMA;
   HODGKINS-DISEASE; RHEUMATOID-ARTHRITIS; BURKITTS-LYMPHOMA;
   ANGIOIMMUNOBLASTIC LYMPHADENOPATHY; CLINICAL-IMPLICATIONS
AB Epstein-Barr virus (EBV) is a ubiquitous gamma-herpes virus that infects most people but results in life-threatening diseases in only a small subset. Persons who are unable to maintain the virus in its latent state can develop uncontrolled EBV-driven lymphoproliferative disorders and lymphomas. EBV-associated lymphomas are well characterized in patients with known defects in cellular immunity as occurs post-transplantation or HIV/AIDS but are increasingly recognized in patients without overt immunodeficiencies. Improved understanding of the biology of these lymphomas and the role EBV plays in lymphomagenesis offer the opportunity for improved therapies targeted at important signaling pathways and immunotherapy specific against EBV viral antigens. Published by Elsevier Ltd.
C1 [Wilson, Wyndham H.] NCI, Lymphoma Therapeut Sect, Metab Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
   [Roschewski, Mark] Walter Reed Natl Mil Med Ctr, Bethesda, MD 20814 USA.
RP Wilson, WH (reprint author), NCI, Lymphoma Therapeut Sect, Metab Branch, Ctr Canc Res,NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM roschewski@mail.nih.gov; wilsonw@mail.nih.gov
OI Roschewski, Mark/0000-0003-0278-2635
FU NIH
FX All research support comes from the intramural research program of the
   NIH.
NR 95
TC 34
Z9 35
U1 1
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1521-6926
J9 BEST PRACT RES CL HA
JI Best Pract. Res. Clin. Haematol.
PD MAR
PY 2012
VL 25
IS 1
BP 75
EP 89
DI 10.1016/j.beha.2012.01.005
PG 15
WC Hematology
SC Hematology
GA 920YP
UT WOS:000302445500008
PM 22409825
ER

PT J
AU Campbell, TJ
   Tindall, DJ
   Figg, WD
AF Campbell, Tessa J.
   Tindall, Donald J.
   Figg, William D.
TI Dihydrotestosterone synthesis from adrenal precursors does not involve
   testosterone in castration-resistant prostate cancer
SO CANCER BIOLOGY & THERAPY
LA English
DT Editorial Material
DE prostate cancer; DHT; testosterone; 5 alpha-dione; SRD5A1;
   Delta(4)-androstenedione; DHEA
ID ANDROGENS
AB Androgen deprivation therapy is the frontline treatment for metastatic prostate cancer; however, because the majority of cases of advanced prostate cancer progress to castration-resistant prostate cancer (CRPC), there is a considerable need to better understand the synthesis of intratumoral concentrations of the androgen receptor (AR) agonist, 5 alpha-dihydrotestosterone (DHT) in CRPC. In a recent article in the Proceedings of the National Academy of Sciences, Chang et al. show that, contrary to widely held assumptions, the dominant pathway to DHT synthesis does not involve testosterone as a precursor to DHT, but instead involves the conversion of Delta(4)-androstenedione (AD) to 5 alpha-dione (AD -> 5 alpha-dione. DHT) by the steroid-5 alpha-reductase isoenzyme 1 (SRD5A1). The authors show that it is this alternative pathway that drives the progression of CRPC, and they confirm these findings in six established human prostate cancer cell lines as well as in the metastatic tumors from two patients with CRPC. Such findings open the door to new areas of research and to the development of new therapeutic targets in CRPC.
C1 [Campbell, Tessa J.; Figg, William D.] NCI, Mol Pharmacol Sect, Med Oncol Branch, Bethesda, MD 20892 USA.
   [Tindall, Donald J.] Mayo Clin, Coll Med, Dept Urol, Rochester, MN USA.
   [Figg, William D.] NCI, Clin Pharmacol Sect, Med Oncol Branch, Bethesda, MD 20892 USA.
RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, Med Oncol Branch, Bethesda, MD 20892 USA.
EM wdfigg@helix.nih.gov
RI Figg Sr, William/M-2411-2016
NR 8
TC 2
Z9 2
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 MAR 1
PY 2012
VL 13
IS 5
BP 237
EP 238
DI 10.4161/cbt.13.5.19608
PG 2
WC Oncology
SC Oncology
GA 905VY
UT WOS:000301305500001
PM 22336886
ER

PT J
AU Chao, J
   Synold, TW
   Morgan, RJ
   Kunos, C
   Longmate, J
   Lenz, HJ
   Lim, D
   Shibata, S
   Chung, V
   Stoller, RG
   Belani, CP
   Gandara, DR
   McNamara, M
   Gitlitz, BJ
   Lau, DH
   Ramalingam, SS
   Davies, A
   Espinoza-Delgado, I
   Newman, EM
   Yen, Y
AF Chao, Joseph
   Synold, Timothy W.
   Morgan, Robert J., Jr.
   Kunos, Charles
   Longmate, Jeff
   Lenz, Heinz-Josef
   Lim, Dean
   Shibata, Stephen
   Chung, Vincent
   Stoller, Ronald G.
   Belani, Chandra P.
   Gandara, David R.
   McNamara, Mark
   Gitlitz, Barbara J.
   Lau, Derick H.
   Ramalingam, Suresh S.
   Davies, Angela
   Espinoza-Delgado, Igor
   Newman, Edward M.
   Yen, Yun
TI A phase I and pharmacokinetic study of oral
   3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249)
   in the treatment of advanced-stage solid cancers: a California Cancer
   Consortium Study
SO CANCER CHEMOTHERAPY AND PHARMACOLOGY
LA English
DT Article
DE 3-AP; Phase I trial; Oral triapine; Ribonucleotide reductase
ID GYNECOLOGIC-ONCOLOGY-GROUP; ADVANCED CERVICAL-CANCER; RIBONUCLEOTIDE
   REDUCTASE; DNA-DAMAGE; RESTING CELLS; TRIAL; HYDROXYUREA; CISPLATIN;
   RADIATION; PROTEIN
AB Background 3-Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) is a novel small-molecule ribonucleotide reductase inhibitor. This study was designed to estimate the maximum tolerated dose (MTD) and oral bioavailability of 3-AP in patients with advanced-stage solid tumors.
   Methods Twenty patients received one dose of intravenous and subsequent cycles of oral 3-AP following a 3 ? 3 patient dose escalation. Intravenous 3-AP was administered to every patient at a fixed dose of 100 mg over a 2-h infusion 1 week prior to the first oral cycle. Oral 3-AP was administered every 12 h for 5 consecutive doses on days 1-3, days 8-10, and days 15-17 of every 28-day cycle. 3-AP was started at 50 mg with a planned dose escalation to 100, 150, and 200 mg. Dose-limiting toxicities (DLT) and bioavailability were evaluated.
   Results Twenty patients were enrolled. For dose level 1 (50 mg), the second of three treated patients had a DLT of grade 3 hypertension. In the dose level 1 expansion cohort, three patients had no DLTs. No further DLTs were encountered during escalation until the 200-mg dose was reached. At the 200 mg 3-AP dose level, two treated patients had DLTs of grade 3 hypoxia. One additional DLT of grade 4 febrile neutropenia was subsequently observed at the de-escalated 150 mg dose. One DLT in 6 evaluable patients established the MTD as 150 mg per dose on this dosing schedule. Responses in the form of stable disease occurred in 5 (25%) of 20 patients. The oral bioavailability of 3-AP was 67 +/- 29% and was consistent with the finding that the MTD by the oral route was 33% higher than by the intravenous route.
   Conclusions Oral 3-AP is well tolerated and has an MTD similar to its intravenous form after accounting for the oral bioavailability. Oral 3-AP is associated with a modest clinical benefit rate of 25% in our treated patient population with advanced solid tumors.
C1 [Chao, Joseph; Synold, Timothy W.; Morgan, Robert J., Jr.; Longmate, Jeff; Lim, Dean; Shibata, Stephen; Chung, Vincent; Newman, Edward M.; Yen, Yun] City Hope Natl Med Ctr, Duarte, CA 91010 USA.
   [Kunos, Charles] Case Western Reserve Univ, Cleveland, OH 44106 USA.
   [Lenz, Heinz-Josef; McNamara, Mark; Gitlitz, Barbara J.] Univ So Calif, Norris Canc Ctr, Los Angeles, CA USA.
   [Stoller, Ronald G.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
   [Belani, Chandra P.] Penn State Hershey Canc Inst, Hershey, PA USA.
   [Gandara, David R.; Lau, Derick H.] Univ Calif Davis, Ctr Canc, Sacramento, CA 95817 USA.
   [Ramalingam, Suresh S.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA.
   [Davies, Angela] OSI Pharmaceut, Ardsley, NY USA.
   [Espinoza-Delgado, Igor] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Yen, Y (reprint author), City Hope Natl Med Ctr, Bldg Room 4117,1500 E Duarte Rd, Duarte, CA 91010 USA.
EM yyen@coh.org
OI Belani, Chandra/0000-0001-5049-5329; Longmate,
   Jeffrey/0000-0002-0869-7928
FU National Institutes of Health, National Cancer Institute [U01 CA62505,
   U01 CA099168]; Cancer Center [P30 CA033572]
FX This study was supported by the National Institutes of Health, National
   Cancer Institute under Cooperative Agreements with the Cancer Therapy
   Evaluation Program (U01 CA62505, City of Hope Medical Center and U01
   CA099168, University of Pittsburgh Cancer Institute) and a Cancer Center
   Support Grant (P30 CA033572, City of Hope Medical Center).
NR 23
TC 14
Z9 14
U1 1
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0344-5704
J9 CANCER CHEMOTH PHARM
JI Cancer Chemother. Pharmacol.
PD MAR
PY 2012
VL 69
IS 3
BP 835
EP 843
DI 10.1007/s00280-011-1779-5
PG 9
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA 919KT
UT WOS:000302325600027
PM 22105720
ER

PT J
AU Hershkowitz, I
   Lamb, ME
   Orbach, Y
   Katz, C
   Horowitz, D
AF Hershkowitz, Irit
   Lamb, Michael E.
   Orbach, Yael
   Katz, Carmit
   Horowitz, Dvora
TI The Development of Communicative and Narrative Skills Among
   Preschoolers: Lessons From Forensic Interviews About Child Abuse
SO CHILD DEVELOPMENT
LA English
DT Article
ID EYEWITNESS MEMORY; DONT UNDERSTAND; AGE-DIFFERENCES; RESPONSES; EVENTS;
   QUESTIONS; TESTIMONY; ACCURACY; RECALL; MIND
AB This study examined age differences in 299 preschoolers responses to investigative interviewers questions exploring the suspected occurrence of child abuse. Analyses focused on the childrens tendencies to respond (a) at all, (b) appropriately to the issue raised by the investigator, and (c) informatively, providing previously undisclosed information. Linear developmental trends characterized all types of responding. When the types of prompts were considered, 3- to 4-year-olds responded slightly more informatively to specific (directive) recall prompts than to open-ended prompts whereas children aged 5 and older were more responsive to open-ended recall prompts. The findings suggest that even 3-year-olds can provide information about experienced events when recall processes are activated, although the ability to provide narrative responses to open-ended recall prompts only becomes reliable later in development.
C1 [Hershkowitz, Irit] Univ Haifa, Sch Social Work, IL-31905 Haifa, Israel.
   [Orbach, Yael] NICHHD, Bethesda, MD USA.
   [Lamb, Michael E.; Katz, Carmit] Univ Cambridge, Cambridge CB2 1TN, England.
RP Hershkowitz, I (reprint author), Univ Haifa, Sch Social Work, IL-31905 Haifa, Israel.
EM irith@research.haifa.ac.il
NR 53
TC 31
Z9 31
U1 8
U2 73
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0009-3920
J9 CHILD DEV
JI Child Dev.
PD MAR-APR
PY 2012
VL 83
IS 2
BP 611
EP 622
DI 10.1111/j.1467-8624.2011.01704.x
PG 12
WC Psychology, Educational; Psychology, Developmental
SC Psychology
GA 908KC
UT WOS:000301488300019
PM 22181976
ER

PT J
AU Blankstein, R
   Ahmed, W
   Bamberg, F
   Rogers, IS
   Schlett, CL
   Nasir, K
   Fontes, J
   Tawakol, A
   Brady, TJ
   Nagurney, JT
   Hoffmann, U
   Truong, QA
AF Blankstein, Ron
   Ahmed, Waleed
   Bamberg, Fabian
   Rogers, Ian S.
   Schlett, Christopher Lothar
   Nasir, Khurram
   Fontes, Joao
   Tawakol, Ahmed
   Brady, Thomas J.
   Nagurney, John T.
   Hoffmann, Udo
   Truong, Quynh A.
TI Comparison of Exercise Treadmill Testing With Cardiac Computed
   Tomography Angiography Among Patients Presenting to the Emergency Room
   With Chest Pain The Rule Out Myocardial Infarction Using
   Computer-Assisted Tomography (ROMICAT) Study
SO CIRCULATION-CARDIOVASCULAR IMAGING
LA English
DT Article
DE cardiovascular CT; exercise testing; coronary artery disease; stress
   testing
ID CORONARY-ARTERY-DISEASE; ASSOCIATION TASK-FORCE; 2002 GUIDELINE UPDATE;
   HEART-ASSOCIATION; AMERICAN-COLLEGE; CARDIOVASCULAR RISK; DEPARTMENT
   PATIENTS; PROGNOSTIC VALUE; TRIAL; CARDIOLOGY
AB Background-The aims of our study were to (1) examine how data from exercise treadmill testing (ETT) can identify patients who have coronary plaque or stenosis, using CT angiography (CTA) as the reference standard, and (2) identify patient characteristics that may be used in selecting ETT versus CTA.
   Methods and Results-The Rule Out Myocardial Infarction Using Computer-Assisted Tomography (ROMICAT) trial was an observational cohort study of acute chest pain patients presenting to the emergency department with normal initial troponin and a nonischemic ECG. Univariate and multivariable analyses were performed to assess the relationship of baseline clinical data and ETT parameters with coronary plaque and stenosis on CTA. Of the 220 patients who had ETT (mean age, 51 years; 63% men), 21 (10%) had positive results. A positive ETT had a sensitivity of 30% and specificity of 93% to detect >50% stenosis. The sensitivity increased to 83% after excluding uninterpretable segments and evaluating the ability to detect a >70% stenosis. Predictors of plaque included older age, male sex, diabetes, hypertension, hyperlipidemia, lower functional capacity, and a lower Duke Treadmill Score. Both a positive ETT and a low Duke Treadmill Score were significant univariate and multivariable predictors of stenosis >50% on CTA Whereas the prevalence of stenosis by CTA was greater among patients with more risk factors, coronary stenosis was not present among men <40 years old or women <50 years old or individuals who achieved at least 13 metabolic equivalents on ETT.
   Conclusions-Among low-to intermediate-risk patients with acute chest pain, a positive ETT has a limited sensitivity but high specificity for the detection of >50% stenosis by CTA. Although patients with a high number of clinical risk factors are more likely to have obstructive coronary artery disease, those who are young or who would be expected to have a very high exercise capacity are unlikely to have coronary stenosis and therefore may benefit from initial ETT testing instead of CTA. (Circ Cardiovasc Imaging. 2012;5:233-242.)
C1 [Blankstein, Ron] Harvard Univ, Brigham & Womens Hosp, Div Cardiovasc, Sch Med,Dept Med, Boston, MA 02115 USA.
   [Nasir, Khurram] Yale Univ, Sect Cardiovasc Med, New Haven, CT USA.
   [Fontes, Joao] NHLBI, Framingham, MA USA.
   [Fontes, Joao] Boston Univ, Framingham Heart Study, Framingham, MA USA.
   [Ahmed, Waleed; Bamberg, Fabian; Rogers, Ian S.; Schlett, Christopher Lothar; Tawakol, Ahmed; Brady, Thomas J.; Hoffmann, Udo; Truong, Quynh A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program, Boston, MA USA.
   [Truong, Quynh A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
   [Tawakol, Ahmed; Brady, Thomas J.; Truong, Quynh A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA.
   [Nagurney, John T.; Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA.
RP Blankstein, R (reprint author), Harvard Univ, Brigham & Womens Hosp, Div Cardiovasc, Sch Med,Dept Med, 75 Francis St,Room Shapiro 5096, Boston, MA 02115 USA.
EM rblankstein@parters.org
FU National Institutes of Health (NIH) [R01 HL080053, T32HL076136,
   K23HL098370, L30HL093896]
FX This work was supported by the National Institutes of Health (NIH) (R01
   HL080053). Drs Blankstein, Ahmed, Rogers, and Truong received support
   from NIH grant T32HL076136. Dr Truong also received support from NIH
   grants K23HL098370 and L30HL093896.
NR 26
TC 16
Z9 16
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-9651
J9 CIRC-CARDIOVASC IMAG
JI Circ.-Cardiovasc. Imaging
PD MAR
PY 2012
VL 5
IS 2
BP 233
EP 242
DI 10.1161/CIRCIMAGING.111.969568
PG 10
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
   Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
   Medical Imaging
GA 916SE
UT WOS:000302122700012
PM 22308274
ER

PT J
AU Barzilay, JI
   Davis, BR
   Pressel, SL
   Cutler, JA
   Einhorn, PT
   Black, HR
   Cushman, WC
   Ford, CE
   Margolis, KL
   Moloo, J
   Oparil, S
   Piller, LB
   Simmons, DL
   Sweeney, ME
   Whelton, PK
   Wong, ND
   Wright, JT
AF Barzilay, Joshua I.
   Davis, Barry R.
   Pressel, Sara L.
   Cutler, Jeffrey A.
   Einhorn, Paula T.
   Black, Henry R.
   Cushman, William C.
   Ford, Charles E.
   Margolis, Karen L.
   Moloo, Jamaluddin
   Oparil, Suzanne
   Piller, Linda B.
   Simmons, Debra L.
   Sweeney, Mary Ellen
   Whelton, Paul K.
   Wong, Nathan D.
   Wright, Jackson T., Jr.
CA ALLHAT Collaborative Res Grp
TI Long-Term Effects of Incident Diabetes Mellitus on Cardiovascular
   Outcomes in People Treated for Hypertension The ALLHAT Diabetes
   Extension Study
SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES
LA English
DT Article
DE cardiovascular diseases; diabetes mellitus; diuretics; mortality
ID LIPID-LOWERING TREATMENT; ATTACK TRIAL ALLHAT; THIAZIDE DIURETICS;
   HEART; PREVENTION; POTASSIUM; THERAPY; RISK; METAANALYSIS; BLOCKER
AB Background-Thiazide-type diuretics are associated with an increased incidence of diabetes compared with other antihypertensive medications. In this study, we determined the long-term cardiovascular disease (CVD) consequences of incident diuretic-associated diabetes compared with the effects of incident diabetes associated with calcium channel blocker and angiotensin-converting enzyme inhibitor use.
   Methods and Results-A total of 22 418 participants from the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) with baseline diabetes, incident diabetes (7.5% with chlorthalidone, 5.6% with amlodipine, and 4.3% with lisinopril), or no diabetes at 2 years of in-trial follow-up were followed for a mean total of 6.9 years (2.9 years in-trial and 4 additional years posttrial) through the use of national databases. The primary outcome was CVD mortality (death from coronary heart disease [CHD], stroke, heart failure, or other CVD). Among other outcomes were all-cause mortality, non-CVD mortality, and CHD (nonfatal myocardial infarction or fatal CHD). Participants on chlorthalidone with incident diabetes versus no diabetes had consistently lower, nonsignificant risk for CVD mortality (hazard ratio [HR], 1.04; 95% CI, 0.74-1.47), all-cause mortality (HR, 1.04; 95% CI, 0.82-1.30), and non-CVD mortality (HR, 1.05; 95% CI, 0.77-1.42) than participants on amlodipine or lisinopril with incident diabetes (HR range, 1.22-1.53). Participants with incident diabetes had elevated CHD risk compared with those with no diabetes (HR, 1.46; 95% CI, 1.09-1.96), but those on chlorthalidone had significantly lower risk than those on lisinopril (HR, 1.18 versus 2.57; P=0.04 for interaction).
   Conclusions-The findings suggest that thiazide-related incident diabetes has less adverse long-term CVD impact than incident diabetes that develops while on other antihypertensive medications.
C1 [Barzilay, Joshua I.] Kaiser Permanente Georgia, Atlanta, GA USA.
   [Barzilay, Joshua I.] Emory Univ, Sch Med, Atlanta, GA USA.
   [Cutler, Jeffrey A.; Einhorn, Paula T.] NHLBI, Bethesda, MD 20892 USA.
   [Black, Henry R.] NYU, Langone Med Ctr, New York, NY USA.
   [Cushman, William C.] Memphis Vet Affairs Med Ctr, Memphis, TN USA.
   [Margolis, Karen L.] HealthPartners Res Fdn, Minneapolis, MN USA.
   [Moloo, Jamaluddin] Univ Colorado, Sch Med, Aurora, CO USA.
   [Oparil, Suzanne] Univ Alabama, Birmingham, AL USA.
   [Simmons, Debra L.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA.
   [Whelton, Paul K.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA.
   [Wong, Nathan D.] Univ Calif Irvine, Irvine, CA USA.
   [Wright, Jackson T., Jr.] Univ Hosp Cleveland, Cleveland, OH 44106 USA.
   [Sweeney, Mary Ellen] Vet Affairs Med Ctr, Decatur, GA 30033 USA.
   [Pressel, Sara L.] Univ Texas Sch Publ Hlth, Coordinating Ctr Clin Trials, Houston, TX 77030 USA.
RP Pressel, SL (reprint author), Univ Texas Sch Publ Hlth, Coordinating Ctr Clin Trials, 1200 Herman Pressler St,Ste W908, Houston, TX 77030 USA.
EM Sara.L.Pressel@uth.tmc.edu
FU National Heart, Lung, and Blood Institute [N01-HC-35130]; Pfizer, Inc.;
   GlaxoSmithKline; Merck; Novartis; Bristol-Myers Squibb; Amgen; Daiichi
   Sankyo; Gilead; Takeda; Forest Pharmaceuticals
FX This study was supported by contract N01-HC-35130 from the National
   Heart, Lung, and Blood Institute. The ALLHAT investigators acknowledge
   contributions of study medications supplied by Pfizer, Inc (amlodipine),
   AstraZeneca (atenolol and lisinopril), and Bristol-Myers Squibb
   (pravastatin) and financial support provided by Pfizer, Inc.; None of
   the authors reports a conflict of interest with regard to the contents
   of this article. The authors report the following financial disclosures:
   Dr Barzilay has held a financial interest in Pfizer and Schering-Plough.
   Dr Black has consulted for Bayer Corporation, Boehringer Ingelheim,
   Bristol-Myers Squibb, CVRx, Daiichi Sankyo, Gilead, Merck, Mitsubishi,
   Novartis, Pfizer, Servier, and Takeda; has received honoraria from
   Bristol-Myers Squibb; and has held a financial interest in Boehringer
   Ingelheim. Dr Davis has consulted for Amgen and Takeda. Dr Cushman has
   consulted for Daiichi Sankyo, Novartis, Noven, Sanofi Aventis, Takeda,
   and Theravance; has received honoraria from Bristol-Myers Squibb,
   Daiichi Sankyo, Novartis, and Sanofi Aventis; and has had research
   grants and contracts with GlaxoSmithKline, Merck, and Novartis. Dr
   Margolis has received research grants from Bristol-Myers Squibb. Dr
   Oparil has consulted for Boehringer Ingelheim, Daiichi Sankyo, Eli
   Lilly, Forest Laboratories, Forest Pharmaceuticals, NicOx, Novartis,
   Omron Healthcare, Pfizer, and Schering-Plough and has received research
   grants from Amgen, Daiichi Sankyo, Gilead, Merck, and Takeda. Dr Sweeney
   has received research grants from GlaxoSmithKline, Merck, and Novartis.
   Dr Wong has received research grants and contracts from Forest
   Pharmaceuticals and Novartis. Dr Wright has consulted for CVRx, Daiichi
   Sankyo, Novartis, and Sanofi Aventis and has received honoraria from
   Sanofi Aventis. Ms Pressel and Drs Cutler, Einhorn, Ford, Moloo, Piller,
   Simmons, and Whelton have no financial interests to report.
NR 16
TC 28
Z9 29
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-7705
J9 CIRC-CARDIOVASC QUAL
JI Circ.-Cardiovasc. Qual. Outcomes
PD MAR
PY 2012
VL 5
IS 2
BP 153
EP U48
DI 10.1161/CIRCOUTCOMES.111.962522
PG 18
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 916RG
UT WOS:000302120300008
PM 22396585
ER

PT J
AU Hsich, EM
   Naftel, DC
   Myers, SL
   Gorodeski, EZ
   Grady, KL
   Schmuhl, D
   Ulisney, KL
   Young, JB
AF Hsich, Eileen M.
   Naftel, David C.
   Myers, Susan L.
   Gorodeski, Eiran Z.
   Grady, Kathleen L.
   Schmuhl, Darlene
   Ulisney, Karen L.
   Young, James B.
TI Should Women Receive Left Ventricular Assist Device Support? Findings
   From INTERMACS
SO CIRCULATION-HEART FAILURE
LA English
DT Article
DE heart failure; heart-assist device; sex; prognosis
ID MECHANICAL CIRCULATORY SUPPORT; IMPLANTATION; TRANSPLANTATION; DATABASE;
   OUTCOMES; GENDER; SEX
AB Background-Small studies have reported women to have worse outcomes and more adverse events after implantation of mechanical circulatory support device compared with men. To further evaluate sex differences in outcome, we used the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS).
   Methods and Results-There were 401 women (pulsatile devices=78) and 1535 men (pulsatile devices=402) from 89 institutions who were prospectively enrolled into the INTERMACS database for primary implantation of a left ventricular assist device (LVAD) between June 23, 2006, and March 31, 2010. Extensive preimplantation and outcome data were collected on all patients. With a mean follow-up of 7 months, 67 females (17%) died and 250 males (16%) died. There was no statistically significant sex difference in mortality for either pulsatile-flow (P=0.82) or continuous-flow (P=0.95) devices in adjusted and unadjusted models. There were also no statistically significant sex differences with time to first infection, bleeding, or device malfunction. However, female sex was associated with an increased hazard of first neurological event (adjusted hazard ratio, 1.44; 95% CI, 1.05-1.96; P=0.020).
   Conclusions-There were no significant sex differences in mortality, time to first infection, bleeding, or device malfunction with either pulsatile- or continuous-flow LVADs. However, women had an increased risk of first neurological event. For urgent/emergent mechanical support, the benefit of LVAD support likely outweighs the risk, but it remains less clear for women undergoing elective LVAD implantation. (Circ Heart Fail. 2012;5:234-240.)
C1 [Hsich, Eileen M.; Gorodeski, Eiran Z.; Schmuhl, Darlene; Young, James B.] Cleveland Clin Fdn, Coll Med, Cleveland, OH 44195 USA.
   [Naftel, David C.; Myers, Susan L.] Univ Alabama, Dept Surg, Birmingham, AL 35294 USA.
   [Grady, Kathleen L.] Northwestern Univ, Dept Surg, Chicago, IL 60611 USA.
   [Ulisney, Karen L.] Natl Heart Lung & Blood Inst, Div Cardiovasc Sci, Bethesda, MD USA.
RP Hsich, EM (reprint author), Cleveland Clin, Kaufman Ctr Heart Failure, Inst Heart & Vasc, J3-4,9500 Euclid Ave, Cleveland, OH 44195 USA.
EM hsiche@ccf.org
OI Gorodeski, Eiran/0000-0003-3756-8831
FU American Heart Association [0730307N]; National Heart, Lung, and Blood
   Institute [HHSN268201100025C]; Cleveland Clinic Kaufman Center for Heart
   Failure
FX This study was supported by American Heart Association Scientist
   Development Grant 0730307N (Dr Hsich), National Heart, Lung, and Blood
   Institute Contract HHSN268201100025C (Drs Naftel and Young and Mss Myers
   and Ulisney), and the Cleveland Clinic Kaufman Center for Heart Failure
   (Drs Hsich and Young and Ms Schmuhl).; Dr Naftel is a consultant to
   Berlin Hearts, Inc, and Syncardia, Inc. Dr Grady receives National
   Heart, Lung, and Blood Institute funding for the Randomized Evaluation
   of VAD InterVEntion before Inotropic Therapy (REVIVE-IT).
NR 21
TC 24
Z9 25
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-3289
J9 CIRC-HEART FAIL
JI Circ.-Heart Fail.
PD MAR
PY 2012
VL 5
IS 2
BP 234
EP 240
DI 10.1161/CIRCHEARTFAILURE.111.963272
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 916RL
UT WOS:000302120800024
PM 22260946
ER

PT J
AU Zannad, F
   Stough, WG
   McMurray, JJV
   Remme, WJ
   Pitt, B
   Borer, JS
   Geller, NL
   Pocock, SJ
AF Zannad, Faiez
   Stough, Wendy Gattis
   McMurray, John J. V.
   Remme, Willem J.
   Pitt, Bertram
   Borer, Jeffrey S.
   Geller, Nancy L.
   Pocock, Stuart J.
TI When to Stop a Clinical Trial Early for Benefit: Lessons Learned and
   Future Approaches
SO CIRCULATION-HEART FAILURE
LA English
DT Article
DE clinical trial; clinical trials data monitoring committees; data
   interpretation; statistical stopping rules for benefit
ID CHRONIC HEART-FAILURE; CARDIAC-RESYNCHRONIZATION THERAPY; DATA
   MONITORING EXPERIENCE; RANDOMIZED-TRIAL; VENTRICULAR-ARRHYTHMIA;
   CARDIOVASCULAR EVENTS; MYOCARDIAL-INFARCTION; HIGH-RISK; MORTALITY;
   MORBIDITY
C1 [Zannad, Faiez] Ctr Hosp Univ, INSERM, Ctr Invest Clin 9501, Nancy, France.
   [Zannad, Faiez] Ctr Hosp Univ, U961, Nancy, France.
   [Zannad, Faiez] Nancy Univ, Dept Cardiol, Nancy, France.
   [Stough, Wendy Gattis] Campbell Univ, Coll Pharm & Hlth Sci, Buies Creek, NC 27506 USA.
   [Stough, Wendy Gattis] Duke Univ, Med Ctr, Durham, NC USA.
   [McMurray, John J. V.] Univ Glasgow, Western Infirm & British Heart Fdn, Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland.
   [Remme, Willem J.] Sticares Cardiovasc Res Inst, Rhoon, Netherlands.
   [Pitt, Bertram] Univ Michigan, Sch Med, Ann Arbor, MI USA.
   [Borer, Jeffrey S.] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA.
   [Borer, Jeffrey S.] Suny Downstate Med Ctr, New York, NY 11203 USA.
   [Geller, Nancy L.] NHLBI, Bethesda, MD 20892 USA.
   [Pocock, Stuart J.] London Sch Hyg & Trop Med, Dept Med Stat, London WC1, England.
RP Zannad, F (reprint author), Hop Jeanne Darc, CIC INSERM CHU, F-54200 Toul, France.
EM f.zannad@chu-nancy.fr
RI Stough, Wendy/R-4287-2016; 
OI Stough, Wendy/0000-0001-8290-1205; mcmurray, john/0000-0002-6317-3975
FU Association de Recherche et d'Information en Cardiologie (ARISC) in
   Nancy, France; Pfizer, Inc; Pfizer
FX This report was generated from discussions during the 7th Global
   Cardiovascular Clinical Trialists (CVCT) Forum held in Paris, France, in
   December 2010. CVCT was organized by the Clinical Investigation Center
   (CIC) Inserm, CHU, and University Henri Poincare of Nancy, France, and
   funded by an unrestricted educational grant from Association de
   Recherche et d'Information en Cardiologie (ARISC), a non-profit
   educational organization, in Nancy, France. ARISC had no involvement in
   writing the manuscript or decisions related to submitting for
   publication.; Dr Zannad was supported by Pfizer, Inc (Steering
   Committee); Dr Gattis Stough: INSERM, Centre d'Investigation Clinique,
   Centre Hospitalier Universitaire, Nancy, France (travel expense
   reimbursement to attend CVCT 2010; professional/project
   management/administrative time related to preparation of this report);
   Dr McMurray: Pfizer (grants, travel expenses, consulting fee related to
   EMPHASIS-HF); Dr Borer: INSERM, Centre d'Investigation Clinique, Centre
   Hospitalier Universitaire, Nancy, France (travel expense reimbursement
   to attend CVCT 2010); Servier, Pfizer, BioMarin, Roche, Novartis, Takeda
   (drug development consulting, membership on DMCs and event adjudication
   entities); Servier (speaking); Servier (payment for manuscript
   preparation); BioMarin (stock/stock options); Dr Geller: INSERM, Centre
   d'Investigation Clinique, Centre Hospitalier Universitaire, Nancy,
   France (travel expense reimbursement to attend CVCT 2010); National
   Heart, Lung, and Blood Institute, Bethesda, MD (employer);
   Francis-Taylor (royalties from 2005 textbook Advanced Topics in Clinical
   Biostatistics); American Statistical Association (professional travel as
   2011 President).
NR 45
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Z9 10
U1 2
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-3289
J9 CIRC-HEART FAIL
JI Circ.-Heart Fail.
PD MAR
PY 2012
VL 5
IS 2
BP 294
EP 302
DI 10.1161/CIRCHEARTFAILURE.111.965707
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 916RL
UT WOS:000302120800031
PM 22438522
ER

PT J
AU Giacoia, GP
   Taylor-Zapata, P
   Zajicek, A
AF Giacoia, George P.
   Taylor-Zapata, Perdita
   Zajicek, Anne
TI Drug Studies in Newborns: A Therapeutic Imperative
SO CLINICS IN PERINATOLOGY
LA English
DT Article
DE Off-patent; Off-label; Drugs; Newborns; Efficacy; Safety
ID INTENSIVE-CARE-UNIT; NEONATAL-RAT BRAIN; BRONCHOPULMONARY DYSPLASIA;
   PRETERM INFANTS; CELL-DEATH; CAFFEINE; ENCEPHALOPATHY; PREMATURE;
   CYTOKINES; SEIZURES
AB Although some drugs have been developed for the neonate, drug development for the least mature and most vulnerable pediatric patients is lacking. Most of the drugs are off-label or off-patent and are empirically administered to newborns once efficacy has been demonstrated in adults and usefulness is suspected or demonstrated in the older pediatric population. Few drugs are approved by the Food and Drug Administration for use in this population. The factors that prevent the demonstration of efficacy and safety in the newborn are discussed and a change in the current approach for neonatal drug studies is suggested.
C1 [Giacoia, George P.; Taylor-Zapata, Perdita; Zajicek, Anne] Obstet & Pediat Pharmacol Branch, Rockville, MD 20852 USA.
   [Giacoia, George P.; Taylor-Zapata, Perdita; Zajicek, Anne] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD 20852 USA.
RP Giacoia, GP (reprint author), 6100 Execut Blvd,Room 4AO1C, Bethesda, MD 20852 USA.
EM giacoiag@mail.nih.gov
NR 47
TC 10
Z9 10
U1 0
U2 3
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0095-5108
EI 1557-9840
J9 CLIN PERINATOL
JI Clin. Perinatol.
PD MAR
PY 2012
VL 39
IS 1
BP 11
EP +
DI 10.1016/j.clp.2011.12.016
PG 14
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 909HH
UT WOS:000301554100004
PM 22341533
ER

PT J
AU Dawson, DA
   Smith, SM
   Pickering, RP
   Grant, BF
AF Dawson, Deborah A.
   Smith, Sharon M.
   Pickering, Roger P.
   Grant, Bridget F.
TI An empirical approach to evaluating the validity of alternative low-risk
   drinking guidelines
SO DRUG AND ALCOHOL REVIEW
LA English
DT Article
DE drinking guideline; alcohol-related harm; validity; prediction
ID BINGE-DRINKING; POPULATION; DEPENDENCE; COLLEGE; HEALTH; ABUSE
AB Introduction and Aims. This paper proposes an approach for evaluating the validity of alternative low-risk drinking guidelines. Design and Methods. Twenty-seven alternative guidelines were evaluated in terms of their ability to predict nine measures of concurrent and prospective alcohol-related harm, using longitudinal data from a nationally representative sample of US adults (n = 26 438 to 12 339 depending upon outcome). Parameters compared included sensitivity, specificity, adjusted odds ratios and measures of model fit. Results. Performance varied by harm. The guidelines that best predicted concurrent alcohol-related harm comprised daily-only limits of 4/3 drinks for men/women, but gender-invariant limits of 4/4 drinks also performed well. Adding weekly limits did little to improve the prediction of concurrent harm. The guidelines that best predicted prospective harm comprised daily limits of 4/4 drinks combined with weekly limits of 14 drinks for men and 7 drinks for women, with weekly limits of 14/14 drinks running second. When concurrent and incident harms were aggregated, daily-only limits of 4/3 drinks performed nearly on a par with the combination of 14/14 drinks per week and 4/3 drinks per day. Discussion and Conclusions. This paper supported gender-specific daily limits and suggested that optimal guidelines might take daily limits from analyses of concurrent harms and weekly limits from analyses of prospective harms. This paper illustrates a mechanism for validating the ability of low-risk drinking guidelines to accurately predict a range of alcohol-related harms, whereby countries could use their own data on consumption and its association with harm to evaluate their low-risk drinking guidelines. [Dawson DA, Smith SM, Pickering RP, Grant BF. An empirical approach to evaluating the validity of alternative low-risk drinking guidelines. Drug Alcohol Rev 2012; 31: 141-150]
C1 [Dawson, Deborah A.; Smith, Sharon M.; Pickering, Roger P.; Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, NIH, Bethesda, MD USA.
RP Dawson, DA (reprint author), NIAAA LEB, Room 3093,5635 Fishers Lane,MSC 9304, Bethesda, MD 20892 USA.
EM ddawson@mail.nih.gov
FU Intramural NIH HHS [Z99 AA999999]
NR 18
TC 13
Z9 13
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0959-5236
J9 DRUG ALCOHOL REV
JI Drug Alcohol Rev.
PD MAR
PY 2012
VL 31
IS 2
SI SI
BP 141
EP 150
DI 10.1111/j.1465-3362.2011.00335.x
PG 10
WC Substance Abuse
SC Substance Abuse
GA 902PD
UT WOS:000301049500004
PM 21954858
ER

PT J
AU Gobl, C
   Tjandra, N
AF Goebl, Christoph
   Tjandra, Nico
TI Application of Solution NMR Spectroscopy to Study Protein Dynamics
SO ENTROPY
LA English
DT Article
DE protein; protein structure; protein dynamics; protein interaction;
   solution NMR spectroscopy
ID PARAMAGNETIC RELAXATION ENHANCEMENT; MAGNETIC-RESONANCE RELAXATION;
   CIS-TRANS ISOMERIZATION; MODEL-FREE APPROACH; CONFORMATIONAL ENTROPY;
   MOLECULAR RECOGNITION; HYDROGEN-EXCHANGE; SIGNALING PROTEIN; STRUCTURAL
   DYNAMICS; REAL-TIME
AB Recent advances in spectroscopic methods allow the identification of minute fluctuations in a protein structure. These dynamic properties have been identified as keys to some biological processes. The consequences of this structural flexibility can be far-reaching and they add a new dimension to the structure-function relationship of biomolecules. Nuclear Magnetic Resonance (NMR) spectroscopy allows the study of structure as well as dynamics of biomolecules in a very broad range of timescales at atomic level. A number of new NMR methods have been developed recently to allow the measurements of time scales and spatial fluctuations, which in turn provide the thermodynamics associated with the biological processes. Since NMR parameters reflect ensemble measurements, structural ensemble approaches in analyzing NMR data have also been developed. These new methods in some instances can even highlight previously hidden conformational features of the biomolecules. In this review we describe several solution NMR methods to study protein dynamics and discuss their impact on important biological processes.
C1 [Tjandra, Nico] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
   [Goebl, Christoph] Graz Univ, Inst Chem Organ & Bioorgan Chem, A-8010 Graz, Austria.
RP Tjandra, N (reprint author), NHLBI, Lab Mol Biophys, NIH, 50 South Dr, Bethesda, MD 20892 USA.
EM christoph.goebl@uni-graz.at; tjandran@nhlbi.nih.gov
RI Goebl, Christoph/G-7578-2016
FU Austrian Science Fund (FWF) [W901-B05]; Austrian Academy of Sciences at
   the Institute of Chemistry at the Karl-Franzens-University of Graz;
   National Heart, Lung, and Blood Institute of NIH
FX C. G. thanks the Austrian Science Fund (FWF) through grant W901-B05 DK:
   Molecular Enzymology and is a grateful recipient of a DOC-fellowship of
   the Austrian Academy of Sciences at the Institute of Chemistry at the
   Karl-Franzens-University of Graz. This work was supported by the
   Intramural Research Program of National Heart, Lung, and Blood Institute
   of NIH to N. T.
NR 51
TC 7
Z9 7
U1 0
U2 18
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1099-4300
J9 ENTROPY-SWITZ
JI Entropy
PD MAR
PY 2012
VL 14
IS 3
BP 581
EP 598
DI 10.3390/e14030581
PG 18
WC Physics, Multidisciplinary
SC Physics
GA 917DS
UT WOS:000302153300011
ER

PT J
AU Sharma, ST
   Nieman, LK
AF Sharma, S. T.
   Nieman, L. K.
TI Prolonged remission after long-term treatment with steroidogenesis
   inhibitors in Cushing's syndrome caused by ectopic ACTH secretion
SO EUROPEAN JOURNAL OF ENDOCRINOLOGY
LA English
DT Article
ID PROOPIOMELANOCORTIN GENE-EXPRESSION; DISEASE; TUMORS; KETOCONAZOLE;
   METHYLATION; METYRAPONE
AB Spontaneous remission is rare in ectopic ACTH syndrome (EAS). We describe four patients with presumed EAS in whom long-term treatment with steroidogenesis inhibitors was followed by prolonged remission of hypercortisolemia. Biochemical testing was consistent with EAS, but imaging failed to identify a tumor. Patients were treated with ketoconazole alone or with mitotane and/or metyrapone to control hypercortisolemia. Dexamethasone was added when a block and replace strategy was used. Treatment with steroidogenesis inhibitors for 3-10 years in these patients was followed by a prolonged period of remission (15-60 months). During remission, the first patient had an elevated ACTH, low cortisol and 24-h urinary free cortisol (UFC), and adrenal atrophy on computerized tomography scan during remission, suggesting a direct toxic effect on the adrenal glands. Cases 2 and 3 had normal to low ACTH levels and low-normal UFC, consistent with an effect at the level of the ectopic tumor. They did not have a history of cyclicity and case 3 has been in remission for similar to 5 years, making cyclic Cushing's syndrome less likely. Case 4, with a history of cyclic hypercortisolism, had normal to slightly elevated ACTH levels and low-normal UFC during remission. The most likely etiology of remission is cyclic production of ACTH by the ectopic tumor. Spontaneous and sustained remission of hypercortisolemia is possible in EAS after long-term treatment with steroidogenesis inhibitors; a drug holiday may be warranted during chronic therapy to evaluate this. The pathophysiology remains unclear but may involve several different mechanisms.
C1 [Sharma, S. T.; Nieman, L. K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
RP Nieman, LK (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bldg 10,CRC,1 East,Rm 3140, Bethesda, MD 20892 USA.
EM sharmast@mail.nih.gov; niemanl@nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
   Development, National Institutes of Health
FX This study was supported by the intramural program of the Eunice Kennedy
   Shriver National Institute of Child Health and Human Development,
   National Institutes of Health.
NR 21
TC 6
Z9 7
U1 0
U2 4
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
   ENGLAND
SN 0804-4643
J9 EUR J ENDOCRINOL
JI Eur. J. Endocrinol.
PD MAR
PY 2012
VL 166
IS 3
BP 531
EP 536
DI 10.1530/EJE-11-0949
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 919QL
UT WOS:000302343200021
PM 22190002
ER

PT J
AU Kiesewetter, DO
   Gao, HK
   Ma, Y
   Niu, G
   Quan, QM
   Guo, N
   Chen, XY
AF Kiesewetter, Dale O.
   Gao, Haokao
   Ma, Ying
   Niu, Gang
   Quan, Qimeng
   Guo, Ning
   Chen, Xiaoyuan
TI F-18-radiolabeled analogs of exendin-4 for PET imaging of GLP-1 in
   insulinoma
SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
LA English
DT Article
DE Exendin-4; GLP-1R; Insulinoma; F-18; PET
ID GLUCAGON-LIKE PEPTIDE-1; PLASMA IN-VITRO; BETA-CELLS; SYNTHETIC
   EXENDIN-4; GLYCEMIC CONTROL; RECEPTOR; EXPRESSION; VIVO; STABILITY;
   PROTEINS
AB Purpose Glucagon-like peptide type 1 (GLP-1) is an incretin peptide that augments glucose-stimulated insulin release following oral consumption of nutrients. Its message is transmitted via a G protein-coupled receptor called GLP-1R, which is colocalized with pancreatic beta-cells. The GLP-1 system is responsible for enhancing insulin release, inhibiting glucagon production, inhibiting hepatic gluconeogenesis, inhibiting gastric mobility, and suppression of appetite. The abundance of GLP-1R in pancreatic beta-cells in insulinoma, a cancer of the pancreas, and the activity of GLP-1 in the cardiovascular system have made GLP-1R a target for molecular imaging.
   Methods We prepared F-18 radioligands for GLP-1R by the reaction of [F-18]FBEM, a maleimide prosthetic group, with [Cys(0)] and [Cys(40)] analogs of exendin-4. The binding affinity, cellular uptake and internalization, in vitro stability, and uptake and specificity of uptake of the resulting compounds were determined in an INS-1 xenograft model in nude mice.
   Results The [F-18] FBEM-[Cys(x)]-exendin-4 analogs were obtained in good yield (34.3 +/- 3.4%, n=11), based on the starting compound [F-18] FBEM), and had a specific activity of 45.51 +/- 16.28 GBq/mu mol (1.23 +/- 0.44 Ci/mu mol, n=7) at the end of synthesis. The C-terminal isomer, [F-18] FBEM[ Cys(40)]-exendin-4, had higher affinity for INS-1 tumor cells (IC50 1.11 +/- 0.057 nM) and higher tumor uptake (25.25 +/- 3.39% ID/g at 1 h) than the N-terminal isomer, [F-18] FBEM[ Cys(0)]-exendin-4 (IC50 2.99 +/- 0.06 nM, uptake 7.20 +/- 1.26 %ID/g at 1 h). Uptake of both isomers into INS-1 tumor, pancreas, stomach, and lung could be blocked by preinjection of nonradiolabeled [Cysx]-exendin-4 (p<0.05).
   Conclusion [F-18] FBEM-[Cys(40)]-exendin-4 and [F-18] FBEM[ Cys(0)]-exendin-4 have high affinity for GLP-1R and display similar in vitro cell internalization. The higher uptake into INS-1 xenograft tumors exhibited by [F-18] FBEM-[Cys(40)]exendin- 4 suggests that this compound would be the better tracer for imaging GLP-1R.
C1 [Kiesewetter, Dale O.; Gao, Haokao; Ma, Ying; Niu, Gang; Quan, Qimeng; Guo, Ning; Chen, Xiaoyuan] NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA.
   [Gao, Haokao] Fourth Mil Med Univ, Xijing Hosp, Dept Cardiol, Xian 710032, Peoples R China.
RP Chen, XY (reprint author), NIBIB, LOMIN, NIH, 31 Ctr Dr,Suite 1 C14, Bethesda, MD 20892 USA.
EM shawn.chen@nih.gov
FU National Institute of Biomedical Imaging and Bioengineering, National
   Institutes of Health
FX This work was supported by the Intramural Research Program of the
   National Institute of Biomedical Imaging and Bioengineering, National
   Institutes of Health. The authors acknowledge the NIH Clinical Center
   PET department for radioisotope production. We thank Dr. Henry S. Eden
   for proof-reading the manuscript.
NR 29
TC 46
Z9 47
U1 4
U2 15
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1619-7070
J9 EUR J NUCL MED MOL I
JI Eur. J. Nucl. Med. Mol. Imaging
PD MAR
PY 2012
VL 39
IS 3
BP 463
EP 473
DI 10.1007/s00259-011-1980-0
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 918YI
UT WOS:000302287200013
PM 22170321
ER

PT J
AU Zanotti-Fregonara, P
   Innis, RB
AF Zanotti-Fregonara, Paolo
   Innis, Robert B.
TI Suggested pathway to assess radiation safety of C-11-labeled PET tracers
   for first-in-human studies
SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
LA English
DT Letter
ID WHOLE-BODY BIODISTRIBUTION; POSITRON-EMISSION-TOMOGRAPHY;
   HEALTHY-VOLUNTEERS; IMAGING AGENT; DOSIMETRY; HUMANS; RADIOLIGAND;
   LIGAND; RECEPTORS; C-11-PIB
C1 [Zanotti-Fregonara, Paolo; Innis, Robert B.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
RP Innis, RB (reprint author), NIMH, Mol Imaging Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM robert.innis@nih.gov
FU Intramural NIH HHS [Z99 MH999999]
NR 40
TC 18
Z9 18
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1619-7070
J9 EUR J NUCL MED MOL I
JI Eur. J. Nucl. Med. Mol. Imaging
PD MAR
PY 2012
VL 39
IS 3
BP 544
EP 547
DI 10.1007/s00259-011-2005-8
PG 4
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 918YI
UT WOS:000302287200023
PM 22160195
ER

PT J
AU Cai, LS
   Xu, R
   Guo, XL
   Pike, VW
AF Cai, Lisheng
   Xu, Rong
   Guo, Xuelei
   Pike, Victor W.
TI Rapid Room-Temperature 11C-Methylation of Arylamines with [11C]Methyl
   Iodide Promoted by Solid Inorganic-Bases in DMF
SO EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
LA English
DT Article
DE Methylation; Arylamine; Ultrasound; Isotopic labeling; Carbon-11;
   Radiopharmaceuticals; Synthesis design
ID POSITRON-EMISSION-TOMOGRAPHY; SYNTHETIC ORGANIC-CHEMISTRY;
   PHASE-TRANSFER CATALYSIS; PROTEIN-KINASE-C; N-ALKYLATION;
   SECONDARY-AMINES; AROMATIC-AMINES; ULTRASOUND; C-11;
   N,N-DIMETHYLFORMAMIDE
AB [11C]Methyl iodide is the most widely used reagent for labeling radiotracers with carbon-11 (t1/2 = 20.4 min) for molecular imaging with positron emission tomography. However, some substrates for labeling, especially primary arylamines and pyrroles, are sluggishly reactive towards [11C]methyl iodide. We found that insoluble inorganic bases, especially Li3N or Li2O, effectively promote rapid reactions (= 10 min) of such substrates with no-carrier-added [11C]methyl iodide in N,N-dimethylformamide (DMF) at room temperature to give 11C-methylated products in useful radiochemical yields. In particular, we discovered that some primary arylamines in Li3N/DMF were converted into their corresponding formanilides, and that these were readily N-methylated with [11C]methyl iodide, which preceded easy basic hydrolysis to the desired [11C]N-methyl secondary arylamines. The use of a solid base permitted selective reaction at an arylamino group and, in some cases, avoided undesirable side reactions, such as ester group hydrolysis. An ultrasound device proved useful to provide remote and constant agitation of the radioactive heterogeneous reaction mixtures but imparted no ultrasound-specific chemical effect.
C1 [Cai, Lisheng; Xu, Rong; Guo, Xuelei; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
RP Cai, LS (reprint author), NIMH, Mol Imaging Branch, NIH, 10 Ctr Dr,Bldg 10,Room B3 C346A, Bethesda, MD 20892 USA.
EM LishengCai@mail.nih.gov
FU National Institutes of Health (NIH) (National Institute of Mental
   Health)
FX This research was supported by the Intramural Research Program of the
   National Institutes of Health (NIH) (National Institute of Mental
   Health). We are grateful to the NIH Clinical Center PET Department
   (Chief: Dr. P. Herscovitch) for the production of carbon-11.
NR 52
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U1 1
U2 17
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY
SN 1434-193X
J9 EUR J ORG CHEM
JI Eur. J. Org. Chem.
PD MAR
PY 2012
IS 7
BP 1303
EP 1310
DI 10.1002/ejoc.201101499
PG 8
WC Chemistry, Organic
SC Chemistry
GA 897QY
UT WOS:000300670800007
PM 24659907
ER

PT J
AU Becker, MR
   Lammermann, T
   Feng, X
   Igyarto, BZ
   Kaplan, DH
   Tessarollo, L
   Germain, RN
   Udey, MC
AF Becker, M. R.
   Lammermann, T.
   Feng, X.
   Igyarto, B. Z.
   Kaplan, D. H.
   Tessarollo, L.
   Germain, R. N.
   Udey, M. C.
TI Langerhans cell-selective deletion of EpCAM (CD326) attenuates
   langerhans cell motility and migration in vivo and enhances contact
   hypersensitivity reactions
SO EXPERIMENTAL DERMATOLOGY
LA English
DT Meeting Abstract
CT 39th Annual Meeting of the Arbeitsgemeinschaft-Dermatologische-Forschung
   (ADF)
CY MAR 01-03, 2012
CL Marburg, GERMANY
SP Arbeitsgemeinsch Dermatol Forsch (ADF)
C1 [Becker, M. R.; Feng, X.; Udey, M. C.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Becker, M. R.] Univ Heidelberg, Dept Dermatol, D-6900 Heidelberg, Germany.
   [Lammermann, T.; Germain, R. N.] NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
   [Igyarto, B. Z.; Kaplan, D. H.] Univ Minnesota, Dept Dermatol, Ctr Immunol, Minneapolis, MN 55455 USA.
   [Tessarollo, L.] NCI, Mouse Canc Genet Program, Ctr Canc Res, NIH, Frederick, MD 21701 USA.
RI Kaplan, Daniel/N-2779-2013
OI Kaplan, Daniel/0000-0002-7851-7320
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 0906-6705
J9 EXP DERMATOL
JI Exp. Dermatol.
PD MAR
PY 2012
VL 21
IS 3
BP e29
EP e29
PG 1
WC Dermatology
SC Dermatology
GA 900ZP
UT WOS:000300931700168
ER

PT J
AU Eberle, FC
   Song, JY
   Xi, L
   Raffeld, M
   Harris, NL
   Wilson, WH
   Pittaluga, S
   Jaffe, ES
AF Eberle, F. C.
   Song, J. Y.
   Xi, L.
   Raffeld, M.
   Harris, N. L.
   Wilson, W. H.
   Pittaluga, S.
   Jaffe, E. S.
TI Transformed cutaneous CD30 positive T-cell lymphoma of the lymph node
   mimicking classical Hodgkin lymphoma
SO EXPERIMENTAL DERMATOLOGY
LA English
DT Meeting Abstract
CT 39th Annual Meeting of the Arbeitsgemeinschaft-Dermatologische-Forschung
   (ADF)
CY MAR 01-03, 2012
CL Marburg, GERMANY
SP Arbeitsgemeinsch Dermatol Forsch (ADF)
C1 [Eberle, F. C.] Univ Tubingen, Dept Dermatol, D-72074 Tubingen, Germany.
   [Eberle, F. C.; Song, J. Y.; Xi, L.; Raffeld, M.; Pittaluga, S.; Jaffe, E. S.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
   [Harris, N. L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
   [Harris, N. L.] Harvard Univ, Sch Med, Boston, MA USA.
   [Wilson, W. H.] NCI, Metab Branch, 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 0906-6705
J9 EXP DERMATOL
JI Exp. Dermatol.
PD MAR
PY 2012
VL 21
IS 3
BP e19
EP e20
PG 2
WC Dermatology
SC Dermatology
GA 900ZP
UT WOS:000300931700114
ER

PT J
AU Elentner, A
   Schmuth, M
   Hermann, M
   Gonzalez, FJ
   Dubrac, S
AF Elentner, A.
   Schmuth, M.
   Hermann, M.
   Gonzalez, F. J.
   Dubrac, S.
TI The pregnane X receptor (PXR) controls Langerhans cell migration via
   CCR7
SO EXPERIMENTAL DERMATOLOGY
LA English
DT Meeting Abstract
CT 39th Annual Meeting of the Arbeitsgemeinschaft-Dermatologische-Forschung
   (ADF)
CY MAR 01-03, 2012
CL Marburg, GERMANY
SP Arbeitsgemeinsch Dermatol Forsch (ADF)
C1 [Hermann, M.] Innsbruck Med Sch, Dept Gen & Transplant Surg, KTM ZIT Lab, A-6020 Innsbruck, Austria.
   [Gonzalez, F. J.] NCI, NIH, Lab Metab, Ctr Canc Res, 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 0906-6705
J9 EXP DERMATOL
JI Exp. Dermatol.
PD MAR
PY 2012
VL 21
IS 3
BP e16
EP e16
PG 1
WC Dermatology
SC Dermatology
GA 900ZP
UT WOS:000300931700092
ER

PT J
AU Kristinsson, SY
   Landgren, O
AF Kristinsson, Sigurdur Yngvi
   Landgren, Ola
TI Thromboprophylaxis in multiple myeloma: is the evidence there?
SO EXPERT REVIEW OF ANTICANCER THERAPY
LA English
DT Editorial Material
DE aspirin; lenalidomide; low-molecular-weight heparin; MGUS; multiple
   myeloma; prophylaxis; thalidomide; venous thromboembolism; warfarin
ID DEEP VENOUS THROMBOSIS; UNDETERMINED SIGNIFICANCE; MONOCLONAL
   GAMMOPATHY; PULMONARY-EMBOLISM; PLUS DEXAMETHASONE; VEIN THROMBOSIS;
   THALIDOMIDE; PREVENTION; LENALIDOMIDE; ASPIRIN
C1 [Kristinsson, Sigurdur Yngvi] Karolinska Univ Hosp, Karolinska Inst, Dept Med, Div Hematol, SE-17176 Stockholm, Sweden.
   [Landgren, Ola] NCI, NIH, Bethesda, MD 20892 USA.
RP Kristinsson, SY (reprint author), Karolinska Univ Hosp, Karolinska Inst, Dept Med, Div Hematol, SE-17176 Stockholm, Sweden.
EM sigurdur.kristinsson@karolinska.se
RI Kristinsson, Sigurdur /M-2910-2015
OI Kristinsson, Sigurdur /0000-0002-4964-7476
NR 23
TC 1
Z9 1
U1 0
U2 1
PU EXPERT REVIEWS
PI LONDON
PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB,
   ENGLAND
SN 1473-7140
J9 EXPERT REV ANTICANC
JI Expert Rev. Anticancer Ther
PD MAR
PY 2012
VL 12
IS 3
BP 291
EP 294
DI 10.1586/ERA.11.214
PG 4
WC Oncology
SC Oncology
GA 915QH
UT WOS:000302042000001
PM 22369320
ER

PT J
AU Hoskins, LM
   Roy, KM
   Greene, MH
AF Hoskins, Lindsey M.
   Roy, Kevin M.
   Greene, Mark H.
TI Toward a New Understanding of Risk Perception Among Young Female BRCA1/2
   "Previvors"
SO FAMILIES SYSTEMS & HEALTH
LA English
DT Article
DE BRCA1; BRCA2; risk perception; breast/ovarian cancer risk; qualitative
   research
ID BREAST-CANCER; COMMUNICATION; MODEL; MUTATIONS; IMPACT; WOMEN
AB The quantitative risk of cancer among BRCA1/2 gene mutation carriers is generally well-understood, and can be communicated clearly to potential and known mutation carriers during the genetic risk assessment, education, and testing process. The extent to which individual mutation carriers feel vulnerable to cancer is a more complex dynamic with a powerful effect on risk-management decision-making; however, these decisions are not the products of straightforward personal assessment of one's quantitative probability of being diagnosed with cancer. We undertook this National Cancer Institute study to broaden understanding of the lived experiences of women who learn early in the life course that they carry a BRCA1/2 mutation. Our data indicate that the relationship between perceived risk and risk-management decisions is not direct, that is, several nononcologic components of risk are also integral to women's management decision-making. High-risk women commonly utilize self-perceived cancer risk to shape their decision-making and communication about various tasks of young adulthood, including differentiation from family of origin, establishing a permanent couple relationship, and family formation. Risk-management is also an important domain in which they strive to take control of their lives by actively participating in management choices. By understanding how these complex dynamics fit together, care providers can better guide, counsel, and support high-risk women as they struggle to balance legitimate risk-reduction needs with the desire to live a normal life. Here we present data from our qualitative research to aid in this effort.
C1 [Hoskins, Lindsey M.; Greene, Mark H.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
   [Roy, Kevin M.] Univ Maryland, Sch Publ Hlth, Dept Family Sci, College Pk, MD 20742 USA.
RP Hoskins, LM (reprint author), 6120 Execut Blvd,EPS 7021, Rockville, MD 20852 USA.
EM hoskins1@mail.nih.gov
FU US National Cancer Institute; Westat, Inc, Rockville MD [N02-CP-65504]
FX The authors gratefully acknowledge the generous contributions of our
   participants, who bravely shared their stories to make this research
   possible. The research of Drs. Hoskins and Greene was supported by the
   Intramural Research Program of the US National Cancer Institute, and by
   support services contract N02-CP-65504 with Westat, Inc, Rockville MD.
NR 24
TC 14
Z9 14
U1 0
U2 6
PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA
SN 1091-7527
J9 FAM SYST HEALTH
JI Fam. Syst. Health
PD MAR
PY 2012
VL 30
IS 1
BP 32
EP 46
DI 10.1037/a0027276
PG 15
WC Health Care Sciences & Services; Family Studies; Public, Environmental &
   Occupational Health
SC Health Care Sciences & Services; Family Studies; Public, Environmental &
   Occupational Health
GA 917OP
UT WOS:000302187900003
PM 22429077
ER

PT J
AU Ghany, MG
   Nelson, DR
   Strader, DB
   Thomas, DL
   Seeff, LB
AF Ghany, Marc G.
   Nelson, David R.
   Strader, Doris B.
   Thomas, David L.
   Seeff, Leonard B.
TI An Update on Treatment of Hepatitis C Virus Genotype 1 Infection and
   Viral Load Assessments Reply
SO HEPATOLOGY
LA English
DT Letter
ID ALPHA-2A (40 KD)/RIBAVIRIN
C1 [Ghany, Marc G.] NIDDK, NIH, Liver Dis Branch, Bethesda, MD 20892 USA.
   [Nelson, David R.] Univ Florida, Sect Hepatobiliary Dis, Gainesville, FL USA.
   [Strader, Doris B.] Univ Vermont, Coll Med, Burlington, VT USA.
   [Thomas, David L.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
   [Seeff, Leonard B.] Hill Grp, Bethesda, MD USA.
RP Ghany, MG (reprint author), NIDDK, NIH, Liver Dis Branch, Bethesda, MD 20892 USA.
NR 8
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD MAR
PY 2012
VL 55
IS 3
DI 10.1002/hep.25524
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 897YS
UT WOS:000300699900039
ER

PT J
AU Zink, CF
   Meyer-Lindenberg, A
AF Zink, Caroline F.
   Meyer-Lindenberg, Andreas
TI Human neuroimaging of oxytocin and vasopressin in social cognition
SO HORMONES AND BEHAVIOR
LA English
DT Review
DE Oxytocin; Vasopressin; Neuroimaging; Pharmacological fMRI; Imaging
   genetics; Social cognition; Amygdala; Human
ID RECEPTOR GENE OXTR; HEALTHY CAUCASIAN ADULTS; EXTENDED LIMBIC SYSTEM;
   ARGININE-VASOPRESSIN; FACIAL EXPRESSIONS; AMYGDALA RESPONSE; NEURAL
   CIRCUITRY; INCREASES TRUST; BRAIN RESPONSES; SEX-DIFFERENCES
AB The neuropeptides oxytocin and vasopressin have increasingly been identified as modulators of human social behaviors and associated with neuropsychiatric disorders characterized by social dysfunction, such as autism. Identifying the human brain regions that are impacted by oxytocin and vasopressin in a social context is essential to fully characterize the role of oxytocin and vasopressin in complex human social cognition. Advances in human non-invasive neuroimaging techniques and genetics have enabled scientists to begin to elucidate the neurobiological basis of the influence of oxytocin and vasopressin on human social behaviors. Here we review the findings to-date from investigations of the acute and chronic effects of oxytocin and vasopressin on neural activity underlying social cognitive processes using "pharmacological fMRI" and "imaging genetics", respectively.
   This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior. Published by Elsevier Inc.
C1 [Zink, Caroline F.] NIMH, Genes Cognit & Psychosis Program, NIH, DHHS, Bethesda, MD 20892 USA.
   [Meyer-Lindenberg, Andreas] Cent Inst Mental Hlth, D-68159 Mannheim, Germany.
RP Zink, CF (reprint author), NIMH, Genes Cognit & Psychosis Program, NIH, DHHS, 9000 Rockville Pike,Bldg 10,Room 3C101, Bethesda, MD 20892 USA.
EM zinkc@mail.nih.gov
RI Meyer-Lindenberg, Andreas/H-1076-2011
OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123
FU National Institute of Mental Health; Deutsche Forschungsgemeinschaft
   (DFG) [SFB 636]; Bundesministerium fur Bildung und Forschung (BMBF);
   National Alliance for Research on Schizophrenia and Depression (NARSAD);
   European Union
FX C.F.Z. acknowledges support from the Intramural Research Program of the
   National Institute of Mental Health during the preparation of this
   manuscript. A.M.-L acknowledges grant support from the Deutsche
   Forschungsgemeinschaft (DFG; SFB 636), Bundesministerium fur Bildung und
   Forschung (BMBF; NGFN-MooDs, Bernstein-Programme), European Union
   (NEWMEDS, OPTIMIZE and EU-GEI) and National Alliance for Research on
   Schizophrenia and Depression (NARSAD; Distinguished Investigator Award)
   during the preparation of this manuscript.
NR 87
TC 79
Z9 79
U1 6
U2 54
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0018-506X
J9 HORM BEHAV
JI Horm. Behav.
PD MAR
PY 2012
VL 61
IS 3
SI SI
BP 400
EP 409
DI 10.1016/j.yhbeh.2012.01.016
PG 10
WC Behavioral Sciences; Endocrinology & Metabolism
SC Behavioral Sciences; Endocrinology & Metabolism
GA 919NN
UT WOS:000302334900019
PM 22326707
ER

PT J
AU Pobbe, RLH
   Pearson, BL
   Defensor, EB
   Bolivar, VJ
   Young, WS
   Lee, HJ
   Blanchard, DC
   Blanchard, RJ
AF Pobbe, Roger L. H.
   Pearson, Brandon L.
   Defensor, Erwin B.
   Bolivar, Valerie J.
   Young, W. Scott, III
   Lee, Heon-Jin
   Blanchard, D. Caroline
   Blanchard, Robert J.
TI Oxytocin receptor knockout mice display deficits in the expression of
   autism-related behaviors
SO HORMONES AND BEHAVIOR
LA English
DT Article
DE Autism; Oxytocin receptor; Social behavior; Mouse models
ID VISIBLE BURROW SYSTEM; TF/J MOUSE MODEL; SOCIAL APPROACH BEHAVIORS;
   ULTRASONIC VOCALIZATIONS; AFFILIATIVE BEHAVIOR; SCENT MARKING;
   VASOPRESSIN; GENE; BRAIN; RECOGNITION
AB A wealth of studies has implicated oxytocin (Oxt) and its receptors (Oxtr) in the mediation of social behaviors and social memory in rodents. It has been suggested that failures in this system contribute to deficits in social interaction that characterize autism spectrum disorders (ASD). In the current analyses, we investigated the expression of autism-related behaviors in mice that lack the ability to synthesize the oxytocin receptor itself, Oxtr knockout (KO) mice, as compared to their wild-type (WT) littermates. In the visible burrow system, Oxtr KO mice showed robust reductions in frontal approach, huddling, allo-grooming, and flight, with more time spent alone, and in self-grooming, as compared to WT. These results were corroborated in the three-chambered test: unlike WT, Oxtr KO mice failed to spend more time in the side of the test box containing an unfamiliar CD-1 mouse. In the social proximity test, Oxtr KO mice showed clear reductions in nose to nose and anogenital sniff behaviors oriented to an unfamiliar C57BL/6J (B6) mouse. In addition, our study revealed no differences between Oxtr WT and KO genotypes in the occurrence of motor and cognitive stereotyped behaviors. A significant genotype effect was found in the scent marking analysis, with Oxtr KO mice showing a decreased number of scent marks, as compared to WT. Overall, the present data indicate that the profile for Oxtr KO mice, including consistent social deficits, and reduced levels of communication, models multiple components of the ASD phenotype.
   This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Pobbe, Roger L. H.; Pearson, Brandon L.; Defensor, Erwin B.; Blanchard, D. Caroline; Blanchard, Robert J.] Univ Hawaii, Pacific Biosci Res Ctr, Honolulu, HI 96822 USA.
   [Bolivar, Valerie J.] New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12208 USA.
   [Bolivar, Valerie J.] SUNY Albany, Sch Publ Hlth, Dept Biomed Sci, Albany, NY USA.
   [Young, W. Scott, III] NIMH, Sect Neural Gene Express, NIH, DHHS, Bethesda, MD 20892 USA.
   [Lee, Heon-Jin] Kyungpook Natl Univ, Sch Dent, Dept Oral Microbiol, Taegu, South Korea.
   [Blanchard, D. Caroline] Univ Hawaii, John A Burns Sch Med, Dept Genet & Mol Biol, Honolulu, HI 96822 USA.
   [Blanchard, Robert J.] Univ Hawaii, Dept Psychol, Honolulu, HI 96822 USA.
RP Pobbe, RLH (reprint author), Univ Hawaii, Pacific Biosci Res Ctr, 1993 East West Rd, Honolulu, HI 96822 USA.
EM rogerlh@hawaii.edu
RI Young, W Scott/A-9333-2009; 
OI Young, W Scott/0000-0001-6614-5112; Pearson,
   Brandon/0000-0003-4807-137X; , Heon-Jin/0000-0002-1911-5014
FU NIH [MH081845]; NIMH [Z01-MH-002498-22]
FX This research was supported by the NIH grant MH081845 to RJB and the
   NIMH Intramural Research Program (Z01-MH-002498-22) to WSY. Amy
   Vasconcellos, Larry Oasay, and Samantha O'Hanlon assisted in data
   collection and behavioral scoring.
NR 57
TC 40
Z9 41
U1 2
U2 17
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0018-506X
J9 HORM BEHAV
JI Horm. Behav.
PD MAR
PY 2012
VL 61
IS 3
SI SI
BP 436
EP 444
DI 10.1016/j.yhbeh.2011.10.010
PG 9
WC Behavioral Sciences; Endocrinology & Metabolism
SC Behavioral Sciences; Endocrinology & Metabolism
GA 919NN
UT WOS:000302334900023
PM 22100185
ER

PT J
AU Kaileh, M
   Sen, R
AF Kaileh, Mary
   Sen, Ranjan
TI NF-kappa B function in B lymphocytes
SO IMMUNOLOGICAL REVIEWS
LA English
DT Review
DE NF-?B; B lymphocytes; BCR; function; development
ID CELL ANTIGEN RECEPTOR; BRUTONS TYROSINE KINASE; NUCLEAR EXPORT SIGNAL;
   LIGHT-CHAIN GENES; ACTIVATING FACTOR-RECEPTOR; HUMORAL IMMUNE-RESPONSES;
   PROTEIN-BINDING SITES; C-MYC EXPRESSION; TRANSCRIPTION FACTORS; MARGINAL
   ZONE
AB NF-?B proteins were identified in the search for mechanisms that regulate B-lymphocyte-specific transcription of immunoglobulin ? light chain genes. Twenty-five years later, though the function of the ?B site in the enhancer remains enigmatic, NF-?B proteins have been shown to have important roles in B-cell development, maintenance, and function. In this review, we summarize the functions of NF-?B in B cells. An overview of B-cell biology that identifies stages in the life of B lymphocytes for the general reader is followed by three sections that examine the role of NF-?B family of proteins in B-cell development, mature B-cell survival and B-cell function. We endeavor throughout to suggest mechanisms and implications of the wide-ranging observations that have been made and conclude by highlighting the need to understand NF-?B-mediated gene expression in more depth.
C1 [Kaileh, Mary; Sen, Ranjan] NIA, Gene Regulat Sect, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA.
RP Sen, R (reprint author), NIA, Gene Regulat Sect, Lab Mol Biol & Immunol, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM ranjan.sen@nih.gov
FU NIH, National Institute on Aging (Baltimore, MD)
FX The authors are supported entirely by the Intramural Research Program of
   the NIH, National Institute on Aging (Baltimore, MD). The authors have
   no conflicts of interest to declare.
NR 182
TC 55
Z9 56
U1 1
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0105-2896
J9 IMMUNOL REV
JI Immunol. Rev.
PD MAR
PY 2012
VL 246
SI SI
BP 254
EP 271
DI 10.1111/j.1600-065X.2012.01106.x
PG 18
WC Immunology
SC Immunology
GA 912GI
UT WOS:000301782400017
PM 22435560
ER

PT J
AU Lim, KH
   Yang, YB
   Staudt, LM
AF Lim, Kian-Huat
   Yang, Yibin
   Staudt, Louis M.
TI Pathogenetic importance and therapeutic implications of NF-kappa B in
   lymphoid malignancies
SO IMMUNOLOGICAL REVIEWS
LA English
DT Review
DE lymphoma; multiple myeloma; ABC DLBCL; CARD11; MyD88; B-cell receptor
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; EPSTEIN-BARR-VIRUS; CLASSICAL HODGKIN
   LYMPHOMA; RESPONSIVE INHIBITORY DOMAIN; CHRONIC INFLAMMATORY DISEASE;
   PLASMA-CELL DIFFERENTIATION; ONCOGENIC CARD11 MUTATIONS; GENE-EXPRESSION
   ANALYSIS; TUMOR-SUPPRESSOR GENE; REED-STERNBERG CELLS
AB Derangement of the nuclear factor ?B (NF-?B) pathway initiates and/or sustains many types of human cancer. B-cell malignancies are particularly affected by oncogenic mutations, translocations, and copy number alterations affecting key components the NF-?B pathway, most likely owing to the pervasive role of this pathway in normal B cells. These genetic aberrations cause tumors to be addicted to NF-?B, which can be exploited therapeutically. Since each subtype of lymphoid cancer utilizes different mechanisms to activate NF-?B, several different therapeutic strategies are needed to address this pathogenetic heterogeneity. Fortunately, a number of drugs that block signaling cascades leading to NF-?B are in early phase clinical trials, several of which are already showing activity in lymphoid malignancies.
C1 [Lim, Kian-Huat; Yang, Yibin; Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Staudt, LM (reprint author), NCI, Metab Branch, Ctr Canc Res, NIH, 9000 Rockville Pike Bldg 10,Room 4N114, Bethesda, MD 20892 USA.
EM lstaudt@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 authors
   declare no conflicts of interest.
NR 219
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U1 1
U2 19
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0105-2896
J9 IMMUNOL REV
JI Immunol. Rev.
PD MAR
PY 2012
VL 246
SI SI
BP 359
EP 378
DI 10.1111/j.1600-065X.2012.01105.x
PG 20
WC Immunology
SC Immunology
GA 912GI
UT WOS:000301782400023
PM 22435566
ER

PT J
AU Green, JG
   Avenevoli, S
   Gruber, MJ
   Kessler, RC
   Lakoma, MD
   Merikangas, KR
   Sampson, NA
   Zaslavsky, AM
AF Green, Jennifer Greif
   Avenevoli, Shelli
   Gruber, Michael J.
   Kessler, Ronald C.
   Lakoma, Matthew D.
   Merikangas, Kathleen Ries
   Sampson, Nancy A.
   Zaslavsky, Alan M.
TI Validation of diagnoses of distress disorders in the US National
   Comorbidity Survey Replication Adolescent Supplement (NCS-A)
SO INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH
LA English
DT Article
DE major depressive episode; generalized anxiety disorder; post-traumatic
   stress disorder; WHO Composite International Diagnostic Interview
   (CIDI); US National Comorbidity Survey Replication Adolescent Supplement
   (NCS-A)
ID COMMON MENTAL-DISORDERS; ANXIETY DISORDERS; MAJOR DEPRESSION; COMMUNITY
   SAMPLE; K-SADS; INTERVIEW; CHILDREN; AGREEMENT; VERSION; PARENT
AB Research diagnostic interviews need to discriminate between closely related disorders in order to allow comorbidity among mental disorders to be studied reliably. Yet conventional studies of diagnostic validity generally focus on single disorders and do not examine discriminant validity. The current study examines the validity of fully-structured diagnoses of closely-related distress disorders (generalized anxiety disorder, post-traumatic stress disorder, major depressive episode, and dysthymic disorder) in the lay-administered Composite International Diagnostic Interview Version 3.0 (CIDI) with independent clinical diagnoses based on the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS) in the US National Comorbidity Survey Replication Adolescent Supplement (NCS-A). The NCS-A is a national survey of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) among 10,148 adolescents. A probability sub-sample of 347 of these adolescents and their parents were administered blinded follow-up K-SADS interviews. Good concordance [area under the receiver operating characteristic curve (AUC)] was found between diagnoses based on the CIDI and the K-SADS for generalized anxiety disorder (AUC=0.78), post-traumatic stress disorder (AUC=0.79), and major depressive episode/dysthymic disorder (AUC=0.86). Further, the CIDI was able to effectively discriminate among different types of distress disorders in the sub-sample of respondents with any distress disorder. Copyright (C) 2011 John Wiley & Sons, Ltd.
C1 [Gruber, Michael J.; Kessler, Ronald C.; Lakoma, Matthew D.; Sampson, Nancy A.; Zaslavsky, Alan M.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
   [Green, Jennifer Greif] Boston Univ, Sch Educ, Boston, MA 02215 USA.
   [Avenevoli, Shelli] NIMH, Div Dev Translat Res, Bethesda, MD 20892 USA.
   [Merikangas, Kathleen Ries] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA.
RP Kessler, RC (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA.
EM ncs@hcp.med.harvard.edu
FU National Institute of Mental Health (NIMH) [U01-MH60220, R01-MH66627,
   R01-MH070884, R13-MH066849, R01-MH069864, R01-MH077883]; National
   Institute on Drug Abuse (NIDA) [R01-DA016558]; Substance Abuse and
   Mental Health Services Administration (SAMHSA); Robert Wood Johnson
   Foundation (RWJF) [044780]; John W. Alden Trust; Fogarty International
   Center of the National Institutes of Health [FIRCA R03-TW006481]; John
   D. and Catherine T. MacArthur Foundation; Pfizer Foundation; Pan
   American Health Organization; Astra Zeneca; BristolMyersSquibb; Eli
   Lilly and Company; GlaxoSmithKline; Ortho-McNeil; Pfizer;
   Sanofi-Aventis; Wyeth; Analysis Group Inc.; Bristol-Myers Squibb; Eli
   Lilly Company; EPI-Q; Johnson & Johnson Pharmaceuticals; Ortho-McNeil
   Janssen Scientific Affairs.; Pfizer Inc.; Sanofi-Aventis Groupe; Shire
   US, Inc.
FX The National Comorbidity Survey Replication Adolescent Supplement
   (NCS-A) is supported by the National Institute of Mental Health (NIMH;
   U01-MH60220 and R01-MH66627) with supplemental support from the National
   Institute on Drug Abuse (NIDA), the Substance Abuse and Mental Health
   Services Administration (SAMHSA), the Robert Wood Johnson Foundation
   (RWJF; Grant 044780), and the John W. Alden Trust. 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
   organizations, agencies, or US Government. A complete list of NCS-A
   publications can be found at http://www.hcp.med.harvard.edu/ncs. Send
   correspondence to ncs@hcp.med.harvard.edu. The NCS-A is carried out in
   conjunction with the World Health Organization World Mental Health (WMH)
   Survey Initiative. We thank the staff of the WMH Data Collection and
   Data Analysis Coordination Centers for assistance with instrumentation,
   fieldwork, and consultation on data analysis. The WMH Data Coordination
   Centers have received support from NIMH (R01-MH070884, R13-MH066849,
   R01-MH069864, R01-MH077883), NIDA (R01-DA016558), the Fogarty
   International Center of the National Institutes of Health (FIRCA
   R03-TW006481), the John D. and Catherine T. MacArthur Foundation, the
   Pfizer Foundation, and the Pan American Health Organization. The WMH
   Data Coordination Centers have also received unrestricted educational
   grants from Astra Zeneca, BristolMyersSquibb, Eli Lilly and Company,
   GlaxoSmithKline, Ortho-McNeil, Pfizer, Sanofi-Aventis, and Wyeth. A
   complete list of WMH publications can be found at
   http://www.hcp.med.harvard.edu/wmh/.; Dr Kessler has been a consultant
   for AstraZeneca, Analysis Group, Bristol-Myers Squibb, Cerner-Galt
   Associates, Eli Lilly & Company, GlaxoSmithKline Inc., HealthCore Inc.,
   Health Dialog, Integrated Benefits Institute, John Snow Inc., Kaiser
   Permanente, Matria Inc., Mensante, Merck & Co, Inc., Ortho-McNeil
   Janssen Scientific Affairs, Pfizer Inc., Primary Care Network, Research
   Triangle Institute, Sanofi-Aventis Groupe, Shire US Inc., SRA
   International, Inc., Takeda Global Research & Development, Transcept
   Pharmaceuticals Inc., and Wyeth-Ayerst; has served on advisory boards
   for Appliance Computing II, Eli Lilly & Company, Mindsite, Ortho-McNeil
   Janssen Scientific Affairs, PlusOne Health Management and Wyeth-Ayerst;
   and has had research support for his epidemiological studies from
   Analysis Group Inc., Bristol-Myers Squibb, Eli Lilly & Company, EPI-Q,
   GlaxoSmithKline, Johnson & Johnson Pharmaceuticals, Ortho-McNeil Janssen
   Scientific Affairs., Pfizer Inc., Sanofi-Aventis Groupe, and Shire US,
   Inc. The remaining authors have no competing interests.
NR 35
TC 5
Z9 5
U1 1
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1049-8931
J9 INT J METH PSYCH RES
JI Int. J. Methods Psychiatr. Res.
PD MAR
PY 2012
VL 21
IS 1
BP 41
EP 51
DI 10.1002/mpr.357
PG 11
WC Psychiatry
SC Psychiatry
GA 907QI
UT WOS:000301432000007
PM 22086845
ER

PT J
AU Berna-Erro, A
   Woodard, GE
   Rosado, JA
AF Berna-Erro, A.
   Woodard, G. E.
   Rosado, J. A.
TI Orais and STIMs: physiological mechanisms and disease
SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
LA English
DT Review
DE STIM; Orai; store-operated Ca2+entry; CRAC; immunodeficiency
ID OPERATED CA2+ ENTRY; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; CAPACITATIVE
   CALCIUM-ENTRY; ACTIVATES CRAC CHANNELS; LONG-TERM POTENTIATION; NAADP
   MOBILIZES CA2+; T-CELL-ACTIVATION; ENDOPLASMIC-RETICULUM;
   PLASMA-MEMBRANE; GOLGI-APPARATUS
AB The stromal interaction molecules STIM1 and STIM2 are Ca2+ sensors, mostly located in the endoplasmic reticulum, that detect changes in the intraluminal Ca2+ concentration and communicate this information to plasma membrane store-operated channels, including members of the Orai family, thus mediating store-operated Ca2+ entry (SOCE). Orai and STIM proteins are almost ubiquitously expressed in human cells, where SOCE has been reported to play a relevant functional role. The phenotype of patients bearing mutations in STIM and Orai proteins, together with models of STIM or Orai deficiency in mice, as well as other organisms such as Drosophila melanogaster, have provided compelling evidence on the relevant role of these proteins in cellular physiology and pathology. Orai1-deficient patients suffer from severe immunodeficiency, congenital myopathy, chronic pulmonary disease, anhydrotic ectodermal dysplasia and defective dental enamel calcification. STIM1-deficient patients showed similar abnormalities, as well as autoimmune disorders. This review summarizes the current evidence that identifies and explains diseases induced by disturbances in SOCE due to deficiencies or mutations in Orai and STIM proteins.
C1 [Berna-Erro, A.; Rosado, J. A.] Univ Extremadura, Dept Physiol, Caceres 10003, Spain.
   [Woodard, G. E.] NIDDK, NIH, Bethesda, MD USA.
RP Rosado, JA (reprint author), Univ Extremadura, Dept Physiol, Av Univ S-N, Caceres 10003, Spain.
EM jarosado@unex.es
RI rosado, juan/H-3488-2015
OI rosado, juan/0000-0002-9749-2325
FU MICINN [BFU2010-21043-C02-01]; Junta de Extremadura [GR10010]
FX This work was supported by MICINN grant BFU2010-21043-C02-01 and Junta
   de Extremadura-FEDER (GR10010).
NR 152
TC 17
Z9 17
U1 2
U2 9
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1582-1838
J9 J CELL MOL MED
JI J. Cell. Mol. Med.
PD MAR
PY 2012
VL 16
IS 3
BP 407
EP 424
DI 10.1111/j.1582-4934.2011.01395.x
PG 18
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 899QN
UT WOS:000300831300002
PM 21790973
ER

PT J
AU Shankavaram, UT
   Bredel, M
   Burgan, WE
   Carter, D
   Tofilon, P
   Camphausen, K
AF Shankavaram, Uma T.
   Bredel, Markus
   Burgan, William E.
   Carter, Donna
   Tofilon, Philip
   Camphausen, Kevin
TI Molecular profiling indicates orthotopic xenograft of glioma cell lines
   simulate a subclass of human glioblastoma
SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
LA English
DT Article
DE supervised model; glioblastoma; orthotopic model; cell lines; xenograft
ID GENE-EXPRESSION; IN-VIVO; PHARMACOLOGICAL BLOCKADE; SUBTYPES;
   PROGRESSION; MUTATIONS; PATHWAYS; GROWTH; VITRO; IDH1
AB Cell line models have been widely used to investigate glioblastoma multiforme (GBM) pathobiology and in the development of targeted therapies. However, GBM tumours are molecularly heterogeneous and how cell lines can best model that diversity is unknown. In this report, we investigated gene expression profiles of three preclinical growth models of glioma cell lines, in vitro and in vivo as subcutaneous and intracerebral xenografts to examine which cell line model most resembles the clinical samples. Whole genome DNA microarrays were used to profile gene expression in a collection of 25 high-grade glioblastomas, and comparisons were made to profiles of cell lines under three different growth models. Hierarchical clustering revealed three molecular subtypes of the glioblastoma patient samples. Supervised learning algorithm, trained on glioma subtypes predicted the intracerebral cell line model with one glioma subtype (r = 0.68; 95% bootstrap CI 0.41, 0.46). Survival analysis of enriched gene sets (P < 0.05) revealed 19 biological categories (146 genes) belonging to neuronal, signal transduction, apoptosis- and glutamate-mediated neurotransmitter activation signals that are associated with poor prognosis in this glioma subclass. We validated the expression profiles of these gene categories in an independent cohort of patients from The Cancer Genome Atlas project (r = 0.62, 95% bootstrap CI: 0.42, 0.43). We then used these data to select and inhibit a novel target (glutamate receptor) and showed that LY341595, a glutamate receptor specific antagonist, could prolong survival in intracerebral tumour-implanted mice in combination with irradiation, providing an in vivo cell line system of preclinical studies.
C1 [Shankavaram, Uma T.; Tofilon, Philip; Camphausen, Kevin] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
   [Bredel, Markus] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA.
   [Bredel, Markus] Northwestern Univ, Feinberg Sch Med, NW Brain Tumor Inst, Dept Neurol Surg, Chicago, IL 60611 USA.
   [Burgan, William E.; Carter, Donna] NCI, Mol Radiat Therapeut Branch, NIH, Bethesda, MD 20892 USA.
   [Burgan, William E.; Carter, Donna] NCI, Sci Applicat Int Corp Frederick, Frederick, MD 21701 USA.
RP Camphausen, K (reprint author), NCI, Radiat Oncol Branch, NIH, 10 Ctr Dr,Bldg 10 CRC, Bethesda, MD 20892 USA.
EM camphauk@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
   Cancer Research
FX This research was supported by Intramural Research Program of the
   National Institutes of Health, National Cancer Institute, Center for
   Cancer Research. The costs of publication of this article were defrayed
   in part by the payment of page charges. This article must therefore be
   hereby marked advertisement in accordance with 18 U.S.C. Section 1734
   solely to indicate this fact.
NR 24
TC 14
Z9 14
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1582-1838
J9 J CELL MOL MED
JI J. Cell. Mol. Med.
PD MAR
PY 2012
VL 16
IS 3
BP 545
EP 554
DI 10.1111/j.1582-4934.2011.01345.x
PG 10
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 899QN
UT WOS:000300831300013
PM 21595825
ER

PT J
AU Sitzmann, M
   Weidlich, IE
   Filippov, IV
   Liao, C
   Peach, ML
   Ihlenfeldt, WD
   Karki, RG
   Borodina, YV
   Cachau, RE
   Nicklaus, MC
AF Sitzmann, Markus
   Weidlich, Iwona E.
   Filippov, Igor V.
   Liao, Chenzhong
   Peach, Megan L.
   Ihlenfeldt, Wolf-Dietrich
   Karki, Rajeshri G.
   Borodina, Yulia V.
   Cachau, Raul E.
   Nicklaus, Marc C.
TI PDB Ligand Conformational Energies Calculated Quantum-Mechanically
SO JOURNAL OF CHEMICAL INFORMATION AND MODELING
LA English
DT Article
ID PROTEIN DATA-BANK; DRUG DESIGN; ELECTRON-DENSITY; BOUND LIGANDS;
   BIOACTIVE CONFORMATION; STRUCTURAL INFORMATION; SUBATOMIC RESOLUTION;
   REFINEMENT; BINDING; DATABASE
AB We present here a greatly updated version of an earlier study on the conformational energies of protein ligand complexes in the Protein Data Bank (PDB) [Nicklaus et al. Bioorg. Med. Chem. 1995, 3, 411-428], with the goal of improving on all possible aspects such as number and selection of ligand instances, energy calculations performed, and additional analyses conducted. Starting from about 357,000 ligand instances deposited in the 2008 version of the Ligand Expo database of the experimental 3D coordinates of all small-molecule instances in the PDB, we created a "high-quality" subset of ligand instances by various filtering steps including application of crystallographic quality criteria and structural unambiguousness. Submission of 640 Gaussian 03 jobs yielded a set of about 415 successfully concluded runs. We used a stepwise optimization of internal degrees of freedom at the DFT level of theory with the B3LYP/6-31G(d) basis set and a single-point energy calculation at B3LYP/6-311++G(3df,2p) after each round of (partial) optimization to separate energy changes due to bond length stretches vs bond angle changes vs torsion changes. Even for the most "conservative" choice of all the possible conformational energies- the energy difference between the conformation in which all internal degrees of freedom except torsions have been optimized and the fully optimized conformer significant energy values were found. The range of 0 to similar to 25 kcal/mol was populated quite evenly and independently of the crystallographic resolution. A smaller number of "outliers" of yet higher energies were seen only at resolutions above 1.3 angstrom. The energies showed some correlation with molecular size and flexibility but not with crystallographic quality metrics such as the Cruickshank diffraction-component precision index (DPI) and R-free-R, or with the ligand instance-specific metrics such as occupancy-weighted B-factor (OWAB), real-space R factor (RSR), and real-space correlation coefficient (RSCC). We repeated these calculations with the solvent model IEFPCM, which yielded energy differences that were generally somewhat lower than the corresponding vacuum results but did not produce a qualitatively different picture. Torsional sampling around the crystal conformation at the molecular mechanics level using the MMFF94s force field typically led to an increase in energy.
C1 [Sitzmann, Markus; Weidlich, Iwona E.; Karki, Rajeshri G.; Nicklaus, Marc C.] NCI, Chem Biol Lab, Ctr Canc Res, NIH,DHHS, Frederick, MD 21702 USA.
   [Filippov, Igor V.; Peach, Megan L.] NCI, Basic Sci Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
   [Ihlenfeldt, Wolf-Dietrich] Xemistry GmbH, D-61462 Konigstein, Germany.
   [Borodina, Yulia V.] NIH, Natl Ctr Biotechnol Informat, US Natl Lib Med, Bethesda, MD 20894 USA.
   [Cachau, Raul E.] NCI, Adv Struct Anal Collab, Informat Syst Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Nicklaus, MC (reprint author), NCI, Chem Biol Lab, Ctr Canc Res, NIH,DHHS, 376 Boyles St, Frederick, MD 21702 USA.
EM mn1@helix.nih.gov
RI Nicklaus, Marc/N-4183-2014; 
OI Nicklaus, Marc/0000-0002-4775-7030
FU National Cancer Institute, National Institutes of Health
   [HHSN261200800001E]
FX This study utilized the high-performance computational capabilities of
   the Helix Systems at the National Institutes of Health, Bethesda, MD
   (http://helix.nih.gov). We thank Doug Fox for his help in putting
   together the protocol used in the Gaussian 03 input files for the
   stepwise optimization of the ligand instances. We thank Gerard DVD
   Kleywegt and Mark Harris for making the crystallographic quality data
   from the EDS server available to us. We thank Adel Golovin for making
   close contact data for PDB protein-ligand complexes available to us. We
   thank Paul Hawkins and Greg Warren for insightful discussions. We thank
   John Westbrook for providing us with statistical numbers about PDB
   entries as well as for useful discussions. This project has been funded
   in part with federal funds from the National Cancer Institute, National
   Institutes of Health, under contract HHSN261200800001E. The content of
   this publication does not necessarily reflect the views or policies of
   the Department of Health and Human Services, nor does mention of trade
   names, commercial products, or organizations imply endorsement by the
   U.S. Government.
NR 78
TC 19
Z9 19
U1 0
U2 13
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1549-9596
J9 J CHEM INF MODEL
JI J. Chem Inf. Model.
PD MAR
PY 2012
VL 52
IS 3
BP 739
EP 756
DI 10.1021/ci200595n
PG 18
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Computer Science,
   Information Systems; Computer Science, Interdisciplinary Applications
SC Pharmacology & Pharmacy; Chemistry; Computer Science
GA 913NJ
UT WOS:000301884400010
PM 22303903
ER

PT J
AU Burcaw, LM
   Callaghan, PT
AF Burcaw, Lauren M.
   Callaghan, Paul T.
TI Correlation of the inhomogeneous field as a measure of sample
   heterogeneity
SO JOURNAL OF MAGNETIC RESONANCE
LA English
DT Article
DE Porous media; 2D correlation; Inhomogeneous fields; Transverse
   relaxation; Internal field gradients
ID POROUS-MEDIA; NMR-SPECTROSCOPY; MAGNETIC-FIELD; DIFFUSION
AB In this paper we present a method to determine the pore and grain size heterogeneity using a correlation between the transverse relaxation time and the susceptibility induced inhomogeneous magnetic field. By sing a CPMG echo train, we are able to correlate T-2 with the inhomogeneous internal magnetic field, B-z(i). We first introduce a simple simulation to study the correlation between the internal magnetic field gradient, vertical bar g vertical bar, and B-z(i), where this correlation is analogous to the T-2-B-z(i) correlation with horizontal inversion. We then acquire experimental data from two samples, one a simple bead pack, and the other a more complicated sandstone rock core. We find that indeed this method can indicate the presence of pore and grain size heterogeneities in the sample. Published by Elsevier Inc.
C1 [Burcaw, Lauren M.] NINDS, Bethesda, MD 20892 USA.
   [Callaghan, Paul T.] Victoria Univ Wellington, MacDiarmid Inst Adv Mat & Nanotechnol, Sch Chem & Phys Sci, Wellington, New Zealand.
RP Burcaw, LM (reprint author), NINDS, 10 Ctr Dr,MSC 1063, Bethesda, MD 20892 USA.
EM lauren.burcaw@nih.gov
NR 17
TC 6
Z9 6
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 1090-7807
J9 J MAGN RESON
JI J. Magn. Reson.
PD MAR
PY 2012
VL 216
BP 144
EP 151
DI 10.1016/j.jmr.2012.01.016
PG 8
WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical;
   Spectroscopy
SC Biochemistry & Molecular Biology; Physics; Spectroscopy
GA 919OR
UT WOS:000302338200019
PM 22361270
ER

PT J
AU Bartali, B
   Frongillo, EA
   Stipanuk, MH
   Bandinelli, S
   Salvini, S
   Palli, D
   Morais, JA
   Volpato, S
   Guralnik, JM
   Ferrucci, L
AF Bartali, Benedetta
   Frongillo, Edward A.
   Stipanuk, Martha H.
   Bandinelli, Stefania
   Salvini, Simonetta
   Palli, Domenico
   Morais, Jose A.
   Volpato, Stefano
   Guralnik, Jack M.
   Ferrucci, Luigi
TI Protein Intake and Muscle Strength in Older Persons: Does Inflammation
   Matter?
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE muscle strength; protein intake; inflammatory markers
ID PHYSICAL FUNCTION; WOMEN; INCHIANTI; DECLINE; DISABILITY; PREDICTOR;
   ADULTS; MASS
AB OBJECTIVES: To examine whether protein intake is associated with change in muscle strength in older persons. Because systemic inflammation has been associated with protein catabolism, the study also evaluated whether a synergistic effect exists between protein intake and inflammatory markers on change in muscle strength.
   DESIGN: Longitudinal.
   SETTING: The Invecchiare in Chianti Study.
   PARTICIPANTS: Five hundred and ninety-eight older adults.
   MEASUREMENTS: Knee extension strength was measured at baseline (1998-2000) and during 3-year follow-up (2001-2003) using a handheld dynamometer. Protein intake was assessed using a detailed food frequency questionnaire. The inflammatory markers examined were C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha). RESULTS: The main effect of protein intake on change in muscle strength was not significant. However, a significant interaction was found between protein intake and CRP (P = .003), IL-6 (P =.049), and TNF-alpha (P =.02), indicating that lower protein intake was associated with greater decline in muscle strength in persons with high levels of inflammatory markers.
   CONCLUSION: Lower protein intake was associated with decline in muscle strength in persons with high levels of inflammatory markers. These results may help to understand the factors contributing to decline in muscle strength with aging and to identify the target population of older persons who may benefit from nutritional interventions aimed at preventing or reducing age-associated muscle impairments and its detrimental consequences. J Am Geriatr Soc 60:480-484, 2012.
C1 [Bartali, Benedetta] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA.
   [Bartali, Benedetta] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Frongillo, Edward A.] Univ S Carolina, Arnold Sch Publ Hlth, Dept Hlth Promot Educ & Behav, Columbia, SC 29208 USA.
   [Frongillo, Edward A.; Stipanuk, Martha H.] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA.
   [Bandinelli, Stefania] Tuscany Reg Hlth Agcy, Florence, Italy.
   [Salvini, Simonetta; Palli, Domenico] Canc Res & Prevent Inst, Mol & Nutr Epidemiol Unit, Florence, Italy.
   [Morais, Jose A.] McGill Univ, Div Geriatr Med, MUHC Royal Victoria Hosp, Montreal, PQ, Canada.
   [Volpato, Stefano] Univ Ferrara, Dept Clin & Expt Med, Sect Internal Med Gerontol & Geriatr, I-44100 Ferrara, Italy.
   [Guralnik, Jack M.] Univ Maryland, Sch Med, Div Gerontol, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
   [Ferrucci, Luigi] NIA, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA.
RP Bartali, B (reprint author), Brigham & Womens Hosp, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA.
EM benedetta.bartali@channing.harvard.edu
RI VOLPATO, STEFANO/H-2977-2014; 
OI VOLPATO, STEFANO/0000-0003-4335-6034; PALLI,
   Domenico/0000-0002-5558-2437
FU Italian Ministry of Health [ICS110.1/RF97.71]; U.S. National Institute
   on Aging, National Institutes of Health [263 MD 9164, 263 MD 821336];
   U.S. National Institute on Aging [N.1-AG-1-1, N.1-AG-1-2111]
FX The InCHIANTI study baseline (1998-2000) was supported as a "targeted
   project" (ICS110.1/RF97.71) by the Italian Ministry of Health and the
   U.S. National Institute on Aging, National Institutes of Health
   (Contracts 263 MD 9164 and 263 MD 821336). The InCHIANTI Follow-up
   (2001-2003) was funded by the U.S. National Institute on Aging
   (Contracts N.1-AG-1-1 and N.1-AG-1-2111).
NR 26
TC 18
Z9 19
U1 1
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD MAR
PY 2012
VL 60
IS 3
BP 480
EP 484
DI 10.1111/j.1532-5415.2011.03833.x
PG 5
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 906KM
UT WOS:000301344000011
PM 22283208
ER

PT J
AU Schnermann, J
   Briggs, JP
AF Schnermann, Jurgen
   Briggs, Josephine P.
TI Synthesis and secretion of renin in mice with induced genetic mutations
SO KIDNEY INTERNATIONAL
LA English
DT Review
DE angiotensin; cyclic AMP; kidney development; renin-angiotensin system;
   transgenic mouse
ID NITRIC-OXIDE SYNTHASE; PROTEIN-TYROSINE-PHOSPHATASE; CORTICAL
   CYCLOOXYGENASE-2 EXPRESSION; ANGIOTENSIN-CONVERTING ENZYME;
   BLOOD-PRESSURE REGULATION; RECEPTOR-DEFICIENT MICE; MACULA DENSA;
   KNOCKOUT MICE; JUXTAGLOMERULAR CELLS; PROSTAGLANDIN E-2
AB The juxtaglomerular (JG) cell product renin is rate limiting in the generation of the bioactive octapeptide angiotensin II. Rates of synthesis and secretion of the aspartyl protease renin by JG cells are controlled by multiple afferent and efferent pathways originating in the CNS, cardiovascular system, and kidneys, and making critical contributions to the maintenance of extracellular fluid volume and arterial blood pressure. Since both excesses and deficits of angiotensin II have deleterious effects, it is not surprising that control of renin is secured by a complex system of feedforward and feedback relationships. Mice with genetic alterations have contributed to a better understanding of the networks controlling renin synthesis and secretion. Essential input for the setting of basal renin generation rates is provided by beta-adrenergic receptors acting through cyclic adenosine monophosphate, the primary intracellular activation mechanism for renin mRNA generation. Other major control mechanisms include COX-2 and nNOS affecting renin through PGE2, PGI2, and nitric oxide. Angiotensin II provides strong negative feedback inhibition of renin synthesis, largely an indirect effect mediated by baroreceptor and macula densa inputs. Adenosine appears to be a dominant factor in the inhibitory arms of the baroreceptor and macula densa mechanisms. Targeted gene mutations have also shed light on a number of novel aspects related to renin processing and the regulation of renin synthesis and secretion. Kidney International (2012) 81, 529-538; doi: 10.1038/ki.2011.451; published online 18 January 2012
C1 [Schnermann, Jurgen] NIDDKD, NIH, Bethesda, MD 20892 USA.
   [Briggs, Josephine P.] NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA.
RP Schnermann, J (reprint author), NIDDKD, NIH, 10 Ctr Dr,MSC 1370, Bethesda, MD 20892 USA.
EM jurgens@intra.niddk.nih.gov
RI Briggs, Josephine/B-9394-2009
OI Briggs, Josephine/0000-0003-0798-1190
FU National Institute of Diabetes and Digestive and Kidney Diseases,
   National Institutes of Health, Bethesda, MD
FX Research from the laboratory was supported by intramural funds of the
   National Institute of Diabetes and Digestive and Kidney Diseases,
   National Institutes of Health, Bethesda, MD.
NR 109
TC 10
Z9 11
U1 1
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0085-2538
J9 KIDNEY INT
JI Kidney Int.
PD MAR
PY 2012
VL 81
IS 6
BP 529
EP 538
DI 10.1038/ki.2011.451
PG 10
WC Urology & Nephrology
SC Urology & Nephrology
GA 900ZC
UT WOS:000300930000004
PM 22258323
ER

PT J
AU Torres, VE
   Chapman, AB
   Perrone, RD
   Bae, KT
   Abebe, KZ
   Bost, JE
   Miskulin, DC
   Steinman, TI
   Braun, WE
   Winklhofer, FT
   Hogan, MC
   Oskoui, FR
   Kelleher, C
   Masoumi, A
   Glockner, J
   Halin, NJ
   Martin, DR
   Remer, E
   Patel, N
   Pedrosa, I
   Wetzel, LH
   Thompson, PA
   Miller, JP
   Meyers, CM
   Schrier, RW
AF Torres, Vicente E.
   Chapman, Arlene B.
   Perrone, Ronald D.
   Bae, K. Ty
   Abebe, Kaleab Z.
   Bost, James E.
   Miskulin, Dana C.
   Steinman, Theodore I.
   Braun, William E.
   Winklhofer, Franz T.
   Hogan, Marie C.
   Oskoui, Frederic R.
   Kelleher, Cass
   Masoumi, Amirali
   Glockner, James
   Halin, Neil J.
   Martin, Diego R.
   Remer, Erick
   Patel, Nayana
   Pedrosa, Ivan
   Wetzel, Louis H.
   Thompson, Paul A.
   Miller, J. Philip
   Meyers, Catherine M.
   Schrier, Robert W.
CA HALT PKD Study Grp
TI Analysis of baseline parameters in the HALT polycystic kidney disease
   trials
SO KIDNEY INTERNATIONAL
LA English
DT Article
DE ADPKD; chronic renal disease; kidney volume; polycystic kidney disease;
   renal function
ID LOW-BIRTH-WEIGHT; GROWTH-FACTOR-I; BLOOD-PRESSURE; METABOLIC SYNDROME;
   RENAL-DISEASE; VOLUME PROGRESSION; POSTNATAL-GROWTH; MENSTRUAL-CYCLE;
   SEX-DIFFERENCES; CYST FORMATION
AB HALT PKD consists of two ongoing randomized trials with the largest cohort of systematically studied patients with autosomal dominant polycystic kidney disease to date. Study A will compare combined treatment with an angiotensin-converting inhibitor and receptor blocker to inhibitor alone and standard compared with low blood pressure targets in 558 early-stage disease patients with an eGFR over 60 ml/min per 1.73 m(2). Study B will compare inhibitor-blocker treatment to the inhibitor alone in 486 late-stage patients with eGFR 25-60 ml/min per 1.73 m(2). We used correlation and multiple regression cross-sectional analyses to determine associations of baseline parameters with total kidney, liver, or liver cyst volumes measured by MRI in Study A and eGFR in both studies. Lower eGFR and higher natural log-transformed urine albumin excretion were independently associated with a larger natural log-transformed total kidney volume adjusted for height (ln(HtTKV)). Higher body surface area was independently associated with a higher ln(HtTKV) and lower eGFR. Men had larger height-adjusted total kidney volume and smaller liver cyst volumes than women. A weak correlation was found between the ln(HtTKV) and natural log-transformed total liver volume adjusted for height or natural log liver cyst volume in women only. Women had higher urine aldosterone excretion and lower plasma potassium. Thus, our analysis (1) confirms a strong association between renal volume and functional parameters, (2) shows that gender and other factors differentially affect the development of polycystic disease in the kidney and liver, and (3) suggests an association between anthropomorphic measures reflecting prenatal and/or postnatal growth and disease severity. Kidney International (2012) 81, 577-585; doi: 10.1038/ki.2011.411; published online 28 December 2011
C1 [Torres, Vicente E.] Mayo Clin, Coll Med, Div Nephrol & Hypertens, Rochester, MN 55901 USA.
   [Chapman, Arlene B.; Oskoui, Frederic R.; Martin, Diego R.] Emory Univ, Sch Med, Atlanta, GA USA.
   [Perrone, Ronald D.; Miskulin, Dana C.; Halin, Neil J.] Tufts Med Ctr, Boston, MA USA.
   [Bae, K. Ty; Abebe, Kaleab Z.; Bost, James E.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
   [Steinman, Theodore I.; Pedrosa, Ivan] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
   [Braun, William E.; Remer, Erick] Cleveland Clin, Cleveland, OH 44106 USA.
   [Winklhofer, Franz T.; Wetzel, Louis H.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA.
   [Kelleher, Cass; Masoumi, Amirali; Patel, Nayana; Schrier, Robert W.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA.
   [Thompson, Paul A.] Sanford Res USD, Sioux Falls, SD USA.
   [Miller, J. Philip] Washington Univ, St Louis, MO USA.
   [Meyers, Catherine M.] NIDDK, NIH, Bethesda, MD USA.
RP Torres, VE (reprint author), Mayo Clin, Coll Med, Div Nephrol & Hypertens, Eisenberg S33B,200 1st St SW, Rochester, MN 55901 USA.
EM torres.vicente@mayo.edu
OI Abebe, Kaleab/0000-0002-3644-8419
FU Novartis Pharmaceuticals; National Institute of Diabetes and Digestive
   and Kidney Diseases, National Institutes of Health [DK62408, DK62401,
   DK62410, DK62402, DK62411]; NCRR GCRCs [RR000039, RR00585, RR000054,
   RR000051, RR23940, RR024296]; Centers for Translational Science
   Activities [RR025008, RR024150, RR025752, RR025780, RR024989]; PKD
   Research Foundation
FX VET is an investigator and Chair of the Steering Committee for several
   Otsuka studies on ADPKD, is an investigator in a clinical trial for
   ADPKD sponsored by Novartis Pharmaceuticals, and has served as
   consultant for Wyeth Pharmaceuticals, Hoffman-La Roche, and Primrose
   Therapeutics. RDP is an investigator and member of the Steering
   Committee for several Otsuka studies on ADPKD and is the coordinating
   and site investigator for a clinical trial for ADPKD sponsored by
   Novartis Pharmaceuticals. ABC is an investigator and member of the
   Steering Committee for several Otsuka studies on ADPKD.; This study is
   supported by cooperative agreements (DK62408, DK62401, DK62410, DK62402,
   and DK62411) with the National Institute of Diabetes and Digestive and
   Kidney Diseases, National Institutes of Health, the NCRR GCRCs (RR000039
   Emory University, RR00585 Mayo Clinic, RR000054 Tufts University,
   RR000051 University of Colorado, RR23940 Kansas University, and
   RR024296, Beth Israel Deaconess Medical Center), and the Centers for
   Translational Science Activities at the participating institutions
   (RR025008 Emory University, RR024150 Mayo Clinic, RR025752 Tufts
   University, RR025780 University of Colorado, and RR024989 Cleveland
   Clinic). Support for the study enrollment phase was also provided by
   grants to the participating clinical centers from the PKD Research
   Foundation. Study drugs were donated by Boehringer Ingelheim
   Pharmaceuticals (telmisartan and placebo) and Merck (lisinopril). The
   HALT Study Group is indebted to the study subjects for taking part in
   the study, the Research Program Coordinators and Program Managers at the
   Washington University (Gigi Flynn and Robin Woltman) and University of
   Pittsburgh (Andrea Erfort and Patty Smith), and the study coordinators
   at the clinical centers (Darlene Baker, Julie Driggs, Maria Fishman,
   Stacie Hitchcock, Andee Jolley, Pamela Lanza, Bonnie Maxwell, Pamela
   Morgan, Kristine Otto, Heather Ondler, Linda Perkins, Gertrude Simon,
   Rita Spirko, Diane Watkins) who made this research possible.
NR 68
TC 28
Z9 30
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0085-2538
J9 KIDNEY INT
JI Kidney Int.
PD MAR
PY 2012
VL 81
IS 6
BP 577
EP 585
DI 10.1038/ki.2011.411
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 900ZC
UT WOS:000300930000009
PM 22205355
ER

PT J
AU Arya, S
   Li, X
   Robinson, TE
   Udosen, I
   Chen, C
   Austin, C
   Furling, D
   Hayes, C
   Brook, JD
   Ketley, A
AF Arya, S.
   Li, X.
   Robinson, T. E.
   Udosen, I.
   Chen, C.
   Austin, C.
   Furling, D.
   Hayes, C.
   Brook, J. D.
   Ketley, A.
TI Compound screening in myotonic dystrophy
SO NEUROMUSCULAR DISORDERS
LA English
DT Meeting Abstract
CT United Kingdom Neuromuscular Translational Research Conference
CY MAR 22-23, 2012
CL Newcastle upon Tyne, ENGLAND
SP London Newcastle MRC Ctr Neuromuscular Dis, Muscular Dystrophy Campaign, Genzyme
C1 [Arya, S.; Li, X.; Robinson, T. E.; Udosen, I.; Brook, J. D.; Ketley, A.] Univ Nottingham, Ctr Genet & Genom, Nottingham NG7 2RD, England.
   [Chen, C.; Austin, C.] NIH, NIH Chem Genom Ctr, Bethesda, MD 20892 USA.
   [Furling, D.] Inst Myol, Paris, France.
   [Hayes, C.] Univ Nottingham, Sch Chem, Nottingham NG7 2RD, England.
RI Hayes, Christopher/B-6022-2016
OI Hayes, Christopher/0000-0003-1692-3646
NR 0
TC 0
Z9 0
U1 0
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD MAR
PY 2012
VL 22
SU 1
BP S29
EP S29
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 920SW
UT WOS:000302428800089
ER

PT J
AU Foley, AR
   Broomfield, AA
   Pandraud, A
   Johnson, JO
   Singleton, AB
   Hargreaves, IP
   Land, JM
   Grunewald, S
   Rahman, S
   Clayton, P
   Houlden, H
   Reilly, MM
   Muntoni, F
AF Foley, A. R.
   Broomfield, A. A.
   Pandraud, A.
   Johnson, J. O.
   Singleton, A. B.
   Hargreaves, I. P.
   Land, J. M.
   Grunewald, S.
   Rahman, S.
   Clayton, P.
   Houlden, H.
   Reilly, M. M.
   Muntoni, F.
TI High-dose riboflavin therapy in Brown-Vialetto-Van Laere syndrome:
   clinical and biochemical improvement
SO NEUROMUSCULAR DISORDERS
LA English
DT Meeting Abstract
CT United Kingdom Neuromuscular Translational Research Conference
CY MAR 22-23, 2012
CL Newcastle upon Tyne, ENGLAND
SP London Newcastle MRC Ctr Neuromuscular Dis, Muscular Dystrophy Campaign, Genzyme
C1 [Foley, A. R.; Muntoni, F.] Great Ormond St Hosp Sick Children, Dubowitz Neuromuscular Ctr, London WC1N 3JH, England.
   [Broomfield, A. A.; Rahman, S.; Clayton, P.] UCL Inst Child Hlth, Dept Clin & Mol Genet, London, England.
   [Pandraud, A.; Johnson, J. O.; Houlden, H.; Reilly, M. M.] UCL Inst Neurol, MRC Ctr Neuromuscular Dis, London WC1N 3BG, England.
   [Johnson, J. O.; Singleton, A. B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
   [Hargreaves, I. P.; Land, J. M.] Natl Hosp Neurol & Neurosurg, Neurometab Unit, UCL Inst Neurol, London WC1N 3BG, England.
   [Grunewald, S.] Great Ormond St Hosp Sick Children, Metab Med Unit, London WC1N 3JH, England.
RI Reilly, Mary/C-8482-2013; Houlden, Henry/C-1532-2008; Singleton,
   Andrew/C-3010-2009; Rahman, Shamima/C-5232-2008
OI Houlden, Henry/0000-0002-2866-7777; Rahman, Shamima/0000-0003-2088-730X
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD MAR
PY 2012
VL 22
SU 1
BP S4
EP S4
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 920SW
UT WOS:000302428800004
ER

PT J
AU Pandraud, A
   Johnson, JO
   Singleton, AB
   Clayton, P
   Land, J
   Hargreaves, I
   Foley, AR
   Muntoni, F
   Reilly, MM
   Houlden, H
AF Pandraud, A.
   Johnson, J. O.
   Singleton, A. B.
   Clayton, P.
   Land, J.
   Hargreaves, I.
   Foley, A. R.
   Muntoni, F.
   Reilly, M. M.
   Houlden, H.
TI Genetic and functional investigation of Brown-Vialetto-Van Laere
   syndrome and related neuropathies
SO NEUROMUSCULAR DISORDERS
LA English
DT Meeting Abstract
CT United Kingdom Neuromuscular Translational Research Conference
CY MAR 22-23, 2012
CL Newcastle upon Tyne, ENGLAND
SP London Newcastle MRC Ctr Neuromuscular Dis, Muscular Dystrophy Campaign, Genzyme
C1 [Pandraud, A.; Johnson, J. O.; Hargreaves, I.; Muntoni, F.; Reilly, M. M.; Houlden, H.] Natl Hosp Neurol & Neurosurg, UCL Inst Neurol, MRC Ctr Neuromuscular Dis, London WC1N 3BG, England.
   [Clayton, P.] UCL Inst Child Hlth, Dept Clin & Mol Genet, London, England.
   [Foley, A. R.] UCL Inst Child Hlth, Dubowitz Neuromuscular Ctr, London, England.
   [Johnson, J. O.; Singleton, A. B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
   [Land, J.; Hargreaves, I.] Natl Hosp Neurol & Neurosurg, Neurometab Unit, London WC1N 3BG, England.
RI Reilly, Mary/C-8482-2013; Houlden, Henry/C-1532-2008
OI Houlden, Henry/0000-0002-2866-7777
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD MAR
PY 2012
VL 22
SU 1
BP S19
EP S20
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 920SW
UT WOS:000302428800056
ER

PT J
AU Harry, GJ
   Kraft, AD
AF Harry, G. Jean
   Kraft, Andrew D.
TI Microglia in the developing brain: A potential target with lifetime
   effects
SO NEUROTOXICOLOGY
LA English
DT Review
DE Microglia; Ontogeny; Developmental neurotoxicity; Brain macrophages;
   Pruning
ID CENTRAL-NERVOUS-SYSTEM; TUMOR-NECROSIS-FACTOR; PROMOTES CHOLINERGIC
   DIFFERENTIATION; NITRIC-OXIDE SYNTHASE; HUMAN ADULT MICROGLIA;
   MACROPHAGES IN-VITRO; GLIAL TNF-ALPHA; BONE-MARROW; RAT-BRAIN;
   PARKINSONS-DISEASE
AB Microglia are a heterogenous group of monocyte-derived cells serving multiple roles within the brain, many of which are associated with immune and macrophage like properties. These cells are known to serve a critical role during brain injury and to maintain homeostasis; yet, their defined roles during development have yet to be elucidated. Microglial actions appear to influence events associated with neuronal proliferation and differentiation during development, as well as, contribute to processes associated with the removal of dying neurons or cellular debris and management of synaptic connections. These long-lived cells display changes during injury and with aging that are critical to the maintenance of the neuronal environment over the lifespan of the organism. These processes may be altered by changes in the colonization of the brain or by inflammatory events during development. This review addresses the role of microglia during brain development, both structurally and functionally, as well as the inherent vulnerability of the developing nervous system. A framework is presented considering microglia as a critical nervous system-specific cell that can influence multiple aspects of brain development (e.g., vascularization, synaptogenesis, and myelination) and have a long term impact on the functional vulnerability of the nervous system to a subsequent insult, whether environmental, physical, age-related, or disease-related. Published by Elsevier Inc.
C1 [Harry, G. Jean] NIEHS, Natl Toxicol Program Lab, Res Triangle Pk, NC 27709 USA.
   [Kraft, Andrew D.] US EPA, Natl Ctr Environm Assessment, Off Res & Dev, Washington, DC 20460 USA.
RP Harry, GJ (reprint author), NIEHS, Natl Toxicol Program Lab, MD C1-04,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM harry@niehs.nih.gov
FU Division, National Toxicology Program; National Institute of
   Environmental Health Sciences; National Institutes of Health; U.S.
   Environmental Protection Agency, Office of Research and Development;
   Department of Health and Human Services [1Z01ES101623, ES021164]
FX This research was supported by the Division, National Toxicology
   Program, National Institute of Environmental Health Sciences, National
   Institutes of Health, Department of Health and Human Services
   #1Z01ES101623 and ES021164, and the U.S. Environmental Protection
   Agency, Office of Research and Development. The views expressed in this
   article are those of the authors and they do not necessarily represent
   the views or policies of the National Toxicology Program or the U.S.
   EPA.
NR 205
TC 68
Z9 71
U1 3
U2 24
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0161-813X
J9 NEUROTOXICOLOGY
JI Neurotoxicology
PD MAR
PY 2012
VL 33
IS 2
BP 191
EP 206
DI 10.1016/j.neuro.2012.01.012
PG 16
WC Neurosciences; Pharmacology & Pharmacy; Toxicology
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology
GA 913SK
UT WOS:000301897500007
PM 22322212
ER

PT J
AU Ogg, G
   Chaiworapongsa, T
   Romero, R
   Hussein, Y
   Kusanovic, JP
   Yeo, L
   Kim, CJ
   Hassan, SS
AF Ogg, Giovanna
   Chaiworapongsa, Tinnakorn
   Romero, Roberto
   Hussein, Youssef
   Kusanovic, Juan Pedro
   Yeo, Lami
   Kim, Chong Jai
   Hassan, Sonia S.
TI Placental Lesions Associated With Maternal Underperfusion Are More
   Frequent in Early-Onset Than in Late-Onset Preeclampsia EDITORIAL
   COMMENT
SO OBSTETRICAL & GYNECOLOGICAL SURVEY
LA English
DT Editorial Material
C1 [Ogg, Giovanna] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI 48201 USA.
   NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
   Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
   Pontificia Univ Catolica Chile, Dept Obstet & Gynecol, Santiago, Chile.
   Hosp Dr Sotero del Rio, Ctr Perinatal Res, Santiago, Chile.
   Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA.
RP Ogg, G (reprint author), NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI 48201 USA.
NR 2
TC 0
Z9 0
U1 1
U2 5
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 MAR
PY 2012
VL 67
IS 3
BP 154
EP 155
DI 10.1097/OGX.0b013e31824b7043
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 917LL
UT WOS:000302177800010
ER

PT J
AU Driscoll, MK
   McCann, C
   Kopace, R
   Homan, T
   Fourkas, JT
   Parent, C
   Losert, W
AF Driscoll, Meghan K.
   McCann, Colin
   Kopace, Rael
   Homan, Tess
   Fourkas, John T.
   Parent, Carole
   Losert, Wolfgang
TI Cell Shape Dynamics: From Waves to Migration
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID REACTION-DIFFUSION WAVES; CHEMOTAXIS; LOCOMOTION; ORGANIZATION;
   PSEUDOPODIA; EXTENSION; NAVIGATE; PATTERNS; MOTILITY
AB We observe and quantify wave-like characteristics of amoeboid migration. Using the amoeba Dictyostelium discoideum, a model system for the study of chemotaxis, we demonstrate that cell shape changes in a wave-like manner. Cells have regions of high boundary curvature that propagate from the leading edge toward the back, usually along alternating sides of the cell. Curvature waves are easily seen in cells that do not adhere to a surface, such as cells that are electrostatically repelled from surfaces or cells that extend over the edge of micro-fabricated cliffs. Without surface contact, curvature waves travel from the leading edge to the back of a cell at similar to 35 mu m/min. Non-adherent myosin II null cells do not exhibit these curvature waves. At the leading edge of adherent cells, curvature waves are associated with protrusive activity. Like regions of high curvature, protrusive activity travels along the boundary in a wave-like manner. Upon contact with a surface, the protrusions stop moving relative to the surface, and the boundary shape thus reflects the history of protrusive motion. The wave-like character of protrusions provides a plausible mechanism for the zig-zagging of pseudopods and for the ability of cells both to swim in viscous fluids and to navigate complex three dimensional topography.
C1 [Driscoll, Meghan K.; McCann, Colin; Kopace, Rael; Homan, Tess; Losert, Wolfgang] Univ Maryland, Dept Phys, College Pk, MD 20742 USA.
   [McCann, Colin; Parent, Carole] NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
   [Fourkas, John T.] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA.
   [Fourkas, John T.; Losert, Wolfgang] Univ Maryland, Inst Phys Sci & Technol, College Pk, MD 20742 USA.
RP Driscoll, MK (reprint author), Univ Maryland, Dept Phys, College Pk, MD 20742 USA.
EM wlosert@umd.edu
RI Fourkas, John/B-3500-2009
OI Fourkas, John/0000-0002-4522-9584
FU NSF [PHY0750371]
FX This work was supported by NSF-PoLS grant PHY0750371. The funders had no
   role in study design, data collection and analysis, decision to publish,
   or preparation of the manuscript.
NR 36
TC 35
Z9 35
U1 0
U2 20
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-734X
EI 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD MAR
PY 2012
VL 8
IS 3
AR e1002392
DI 10.1371/journal.pcbi.1002392
PG 10
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA 918IY
UT WOS:000302244000003
PM 22438794
ER

PT J
AU Korkmaz, EN
   Nussinov, R
   Haliloglu, Y
AF Korkmaz, Elif Nihal
   Nussinov, Ruth
   Haliloglu, Yuerkan
TI Conformational Control of the Binding of the Transactivation Domain of
   the MLL Protein and c-Myb to the KIX Domain of CREB
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID TRANSCRIPTION FACTOR-BINDING; MOLECULAR-MECHANICS; COACTIVATOR CBP;
   GENE-EXPRESSION; ALLOSTERY; DYNAMICS; RECOGNITION; COOPERATIVITY;
   CBP/P300; P300/CBP
AB The KIX domain of CBP is a transcriptional coactivator. Concomitant binding to the activation domain of proto-oncogene protein c-Myb and the transactivation domain of the trithorax group protein mixed lineage leukemia (MLL) transcription factor lead to the biologically active ternary MLL: KIX: c-Myb complex which plays a role in Pol II-mediated transcription. The binding of the activation domain of MLL to KIX enhances c-Myb binding. Here we carried out molecular dynamics (MD) simulations for the MLL: KIX: c-Myb ternary complex, its binary components and KIX with the goal of providing a mechanistic explanation for the experimental observations. The dynamic behavior revealed that the MLL binding site is allosterically coupled to the c-Myb binding site. MLL binding redistributes the conformational ensemble of KIX, leading to higher populations of states which favor c-Myb binding. The key element in the allosteric communication pathways is the KIX loop, which acts as a control mechanism to enhance subsequent binding events. We tested this conclusion by in silico mutations of loop residues in the KIX: MLL complex and by comparing wild type and mutant dynamics through MD simulations. The loop assumed MLL binding conformation similar to that observed in the KIX: c-Myb state which disfavors the allosteric network. The coupling with c-Myb binding site faded, abolishing the positive cooperativity observed in the presence of MLL. Our major conclusion is that by eliciting a loop-mediated allosteric switch between the different states following the binding events, transcriptional activation can be regulated. The KIX system presents an example how nature makes use of conformational control in higher level regulation of transcriptional activity and thus cellular events.
C1 [Korkmaz, Elif Nihal; Haliloglu, Yuerkan] Bogazici Univ, Polymer Res Ctr, Istanbul, Turkey.
   [Korkmaz, Elif Nihal; Haliloglu, Yuerkan] Bogazici Univ, Dept Chem Engn, Istanbul, Turkey.
   [Nussinov, Ruth] NCI, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21701 USA.
   [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel.
RP Korkmaz, EN (reprint author), Bogazici Univ, Polymer Res Ctr, Istanbul, Turkey.
EM ruthnu@helix.nih.gov; turkan@prc.boun.edu.tr
FU Scientific and Technological Research Council of Turkey (TUBITAK)
   [110T088]; Betil Fund; Turkish Academy of Sciences (TUBA); National
   Cancer Institute, National Institutes of Health [HHSN261200800001E];
   NIH, National Cancer Institute, Center for Cancer Research
FX We would like to acknowledge financial support from the following
   sources: The Scientific and Technological Research Council of Turkey
   (TUBITAK) with Project No: 110T088, Betil Fund, Turkish Academy of
   Sciences (TUBA). This project has been funded in whole or in part with
   Federal funds from the National Cancer Institute, National Institutes of
   Health, under contract number HHSN261200800001E. The content of this
   publication does not necessarily reflect the views or policies of the
   Department of Health and Human Services, nor does mention of trade
   names, commercial products, or organizations imply endorsement by the
   U.S. Government. This research was supported (in part) by the Intramural
   Research Program of the 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 44
TC 24
Z9 24
U1 2
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-734X
EI 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD MAR
PY 2012
VL 8
IS 3
AR e1002420
DI 10.1371/journal.pcbi.1002420
PG 9
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA 918IY
UT WOS:000302244000028
PM 22438798
ER

PT J
AU Hotez, PJ
   Bottazzi, ME
   Dumonteil, E
   Valenzuela, JG
   Kamhawi, S
   Ortega, J
   Rosales, SPD
   Cravioto, MB
   Tapia-Conyer, R
AF Hotez, Peter J.
   Bottazzi, Maria Elena
   Dumonteil, Eric
   Valenzuela, Jesus G.
   Kamhawi, Shaden
   Ortega, Jaime
   de Leon Rosales, Samuel Ponce
   Betancourt Cravioto, Miguel
   Tapia-Conyer, Roberto
TI Texas and Mexico: Sharing a Legacy of Poverty and Neglected Tropical
   Diseases
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Editorial Material
ID COMBINATION DNA VACCINE; CHAGAS-DISEASE; UNITED-STATES; CUTANEOUS
   LEISHMANIASIS; ANTIPOVERTY VACCINES; ONCHOCERCA-VOLVULUS;
   TRYPANOSOMA-CRUZI; NORTH-AMERICA; DENGUE VIRUS; TRANSMISSION
C1 [Hotez, Peter J.; Bottazzi, Maria Elena] Sabin Vaccine Inst, Houston, TX USA.
   [Hotez, Peter J.; Bottazzi, Maria Elena] Texas Childrens Hosp, Ctr Vaccine Dev, Sect Pediat Trop Med, Dept Pediat, Houston, TX 77030 USA.
   [Hotez, Peter J.; Bottazzi, Maria Elena] Texas Childrens Hosp, Ctr Vaccine Dev, Sect Pediat Trop Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA.
   [Hotez, Peter J.; Bottazzi, Maria Elena] Baylor Coll Med, Natl Sch Trop Med, Houston, TX 77030 USA.
   [Dumonteil, Eric] Autonomous Univ Yucatan UADY, Ctr Invest Reg Dr Hideo Noguchi, Parasitol Lab, Merida, Mexico.
   [Valenzuela, Jesus G.; Kamhawi, Shaden] NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
   [Ortega, Jaime] Inst Politecn Nacl CINVESTAV IPN, Ctr Invest & Estudios Avanzados, Dept Biotecnol & Bioingn, Mexico City, DF, Mexico.
   [de Leon Rosales, Samuel Ponce] Labs Biol & React Mexico BIRMEX, Mexico City, DF, Mexico.
   [Betancourt Cravioto, Miguel; Tapia-Conyer, Roberto] ICSS, Mexico City, DF, Mexico.
RP Hotez, PJ (reprint author), Sabin Vaccine Inst, Houston, TX USA.
EM hotez@bcm.edu
RI Ortega-Lopez, Jaime/A-1364-2008; 
OI Ortega-Lopez, Jaime/0000-0001-9136-9994; Hotez,
   Peter/0000-0001-8770-1042; Dumonteil, Eric/0000-0001-9376-0209
NR 52
TC 24
Z9 26
U1 3
U2 16
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1935-2727
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD MAR
PY 2012
VL 6
IS 3
AR e1497
DI 10.1371/journal.pntd.0001497
PG 6
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 916VU
UT WOS:000302132100004
PM 22479656
ER

PT J
AU Mire, CE
   Miller, AD
   Carville, A
   Westmoreland, SV
   Geisbert, JB
   Mansfield, KG
   Feldmann, H
   Hensley, LE
   Geisbert, TW
AF Mire, Chad E.
   Miller, Andrew D.
   Carville, Angela
   Westmoreland, Susan V.
   Geisbert, Joan B.
   Mansfield, Keith G.
   Feldmann, Heinz
   Hensley, Lisa E.
   Geisbert, Thomas W.
TI Recombinant Vesicular Stomatitis Virus Vaccine Vectors Expressing
   Filovirus Glycoproteins Lack Neurovirulence in Nonhuman Primates
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; MARBURG HEMORRHAGIC-FEVER; EBOLA-VIRUS;
   MEASLES-VIRUS; COMPLETE PROTECTION; POSTEXPOSURE PROTECTION;
   REPLICATION-COMPETENT; MUCOSAL IMMUNIZATION; CYNOMOLGUS MACAQUES;
   GUINEA-PIGS
AB The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. Among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV) that expresses an individual filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). The main concern with all replication-competent vaccines, including the rVSV filovirus GP vectors, is their safety. To address this concern, we performed a neurovirulence study using 21 cynomolgus macaques where the vaccines were administered intrathalamically. Seven animals received a rVSV vector expressing the Zaire ebolavirus (ZEBOV) GP; seven animals received a rVSV vector expressing the Lake Victoria marburgvirus (MARV) GP; three animals received rVSV-wild type (wt) vector, and four animals received vehicle control. Two of three animals given rVSV-wt showed severe neurological symptoms whereas animals receiving vehicle control, rVSV-ZEBOV-GP, or rVSV-MARV-GP did not develop these symptoms. Histological analysis revealed major lesions in neural tissues of all three rVSV-wt animals; however, no significant lesions were observed in any animals from the filovirus vaccine or vehicle control groups. These data strongly suggest that rVSV filovirus GP vaccine vectors lack the neurovirulence properties associated with the rVSV-wt parent vector and support their further development as a vaccine platform for human use.
C1 [Mire, Chad E.; Geisbert, Joan B.; Geisbert, Thomas W.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA.
   [Mire, Chad E.; Geisbert, Joan B.; Geisbert, Thomas W.] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX USA.
   [Miller, Andrew D.; Carville, Angela; Westmoreland, Susan V.; Mansfield, Keith G.] Harvard Univ, Sch Med, Boston, MA USA.
   [Miller, Andrew D.; Westmoreland, Susan V.] New England Primate Res Ctr, Div Comparat Pathol, Southborough, MA USA.
   [Carville, Angela] New England Primate Res Ctr, Dept Pathol, Southborough, MA USA.
   [Mansfield, Keith G.] New England Primate Res Ctr, Div Primate Resources, Southborough, MA USA.
   [Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA.
   [Hensley, Lisa E.] USA, Med Res Inst Infect Dis, Div Virol, Ft Detrick, MD 21702 USA.
RP Mire, CE (reprint author), Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA.
EM lisa.hensley@us.army.mil
FU Defense Threat Reduction Agency; US Army Medical Research Acquisition
   [W81XWH-08-C-0765]
FX This study was funded in part by the Defense Threat Reduction Agency, US
   Army Medical Research Acquisition contract no. W81XWH-08-C-0765 to TWG.
   The funding agency had no role in study design, data collection and
   analysis, decision to publish, or preparation of the manuscript.
NR 68
TC 35
Z9 37
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1935-2727
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD MAR
PY 2012
VL 6
IS 3
AR e1567
DI 10.1371/journal.pntd.0001567
PG 12
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 916VU
UT WOS:000302132100021
PM 22448291
ER

PT J
AU Barrett, BS
   Smith, DS
   Li, SX
   Guo, K
   Hasenkrug, KJ
   Santiago, ML
AF Barrett, Bradley S.
   Smith, Diana S.
   Li, Sam X.
   Guo, Kejun
   Hasenkrug, Kim J.
   Santiago, Mario L.
TI A Single Nucleotide Polymorphism in Tetherin Promotes Retrovirus
   Restriction In Vivo
SO PLOS PATHOGENS
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; CLATHRIN-MEDIATED
   ENDOCYTOSIS; DEHYDROGENASE-ELEVATING VIRUS; PLASMACYTOID DENDRITIC
   CELLS; FRIEND-VIRUS; HIV-1 RELEASE; T-CELLS; INFECTION; VPU
AB Tetherin is a membrane protein of unusual topology expressed from rodents to humans that accumulates enveloped virus particles on the surface of infected cells. However, whether this 'tethering' activity promotes or restricts retroviral spread during acute retrovirus infection in vivo is controversial. We report here the identification of a single nucleotide polymorphism in the Tetherin gene of NZW/LacJ (NZW) mice that mutated the canonical ATG start site to GTG. Translation of NZW Tetherin from downstream ATGs deleted a conserved dual-tyrosine endosomal sorting motif, resulting in higher cell surface expression and more potent inhibition of Friend retrovirus release compared to C57BL/6 (B6) Tetherin in vitro. Analysis of (B6xNZW)F-1 hybrid mice revealed that increased Tetherin cell surface expression in NZW mice is a recessive trait in vivo. Using a classical genetic backcrossing approach, NZW Tetherin expression strongly correlated with decreased Friend retrovirus replication and pathogenesis. However, the protective effect of NZW Tetherin was not observed in the context of B6 Apobec3/Rfv3 resistance. These findings identify the first functional Tetherin polymorphism within a mammalian host, demonstrate that Tetherin cell surface expression is a key parameter for retroviral restriction, and suggest the existence of a restriction factor hierarchy to counteract pathogenic retrovirus infections in vivo.
C1 [Barrett, Bradley S.; Smith, Diana S.; Guo, Kejun; Santiago, Mario L.] Univ Colorado Denver, Dept Med, Aurora, CO USA.
   [Li, Sam X.; Santiago, Mario L.] Univ Colorado Denver, Dept Microbiol, Aurora, CO USA.
   [Hasenkrug, Kim J.] NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
   [Santiago, Mario L.] Univ Colorado Denver, Dept Immunol, Aurora, CO USA.
RP Barrett, BS (reprint author), Univ Colorado Denver, Dept Med, Aurora, CO USA.
EM mario.santiago@ucdenver.edu
OI Santiago, Mario L./0000-0001-7792-2706
FU NIH [R01 AI090795]; UCD; NIAID/NIH
FX This work was supported by a grant from NIH (R01 AI090795), UCD start-up
   funds to MLS and the NIAID/NIH Intramural Research Program to KJH. The
   funders had no role in the study design, data collection and analysis,
   decision to publish or preparation of the manuscript.
NR 49
TC 27
Z9 28
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAR
PY 2012
VL 8
IS 3
AR e1002596
DI 10.1371/journal.ppat.1002596
PG 13
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 918CC
UT WOS:000302225600045
PM 22457621
ER

PT J
AU Levinsohn, JL
   Newman, ZL
   Hellmich, KA
   Fattah, R
   Getz, MA
   Liu, S
   Sastalla, I
   Leppla, SH
   Moayeri, M
AF Levinsohn, Jonathan L.
   Newman, Zachary L.
   Hellmich, Kristina A.
   Fattah, Rasem
   Getz, Matthew A.
   Liu, Shihui
   Sastalla, Inka
   Leppla, Stephen H.
   Moayeri, Mahtab
TI Anthrax Lethal Factor Cleavage of Nlrp1 Is Required for Activation of
   the Inflammasome
SO PLOS PATHOGENS
LA English
DT Article
ID CASPASE-1 ACTIVATION; TOXIN; PROTEOLYSIS; KINASE
AB NOD-like receptor (NLR) proteins (Nlrps) are cytosolic sensors responsible for detection of pathogen and danger-associated molecular patterns through unknown mechanisms. Their activation in response to a wide range of intracellular danger signals leads to formation of the inflammasome, caspase-1 activation, rapid programmed cell death (pyroptosis) and maturation of IL-1 beta and IL-18. Anthrax lethal toxin (LT) induces the caspase-1-dependent pyroptosis of mouse and rat macrophages isolated from certain inbred rodent strains through activation of the NOD-like receptor (NLR) Nlrp1 inflammasome. Here we show that LT cleaves rat Nlrp1 and this cleavage is required for toxin-induced inflammasome activation, IL-1 beta release, and macrophage pyroptosis. These results identify both a previously unrecognized mechanism of activation of an NLR and a new, physiologically relevant protein substrate of LT.
C1 [Levinsohn, Jonathan L.; Newman, Zachary L.; Hellmich, Kristina A.; Fattah, Rasem; Getz, Matthew A.; Liu, Shihui; Sastalla, Inka; Leppla, Stephen H.; Moayeri, Mahtab] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Levinsohn, JL (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
EM mmoayeri@niaid.nih.gov
FU NIH, National Institute of Allergy and Infectious Diseases
FX This research was supported by the Intramural Research Program of the
   NIH, National Institute of Allergy and Infectious Diseases. The funders
   had no role in study design, data collection and analysis, decision to
   publish, or preparation of the manuscript.
NR 20
TC 95
Z9 96
U1 1
U2 15
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAR
PY 2012
VL 8
IS 3
AR e1002638
DI 10.1371/journal.ppat.1002638
PG 7
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 918CC
UT WOS:000302225600060
PM 22479187
ER

PT J
AU Reid, AJ
   Vermont, SJ
   Cotton, JA
   Harris, D
   Hill-Cawthorne, GA
   Konen-Waisman, S
   Latham, SM
   Mourier, T
   Norton, R
   Quail, MA
   Sanders, M
   Shanmugam, D
   Sohal, A
   Wasmuth, JD
   Brunk, B
   Grigg, ME
   Howard, JC
   Parkinson, J
   Roos, DS
   Trees, AJ
   Berriman, M
   Pain, A
   Wastling, JM
AF Reid, Adam James
   Vermont, Sarah J.
   Cotton, James A.
   Harris, David
   Hill-Cawthorne, Grant A.
   Koenen-Waisman, Stephanie
   Latham, Sophia M.
   Mourier, Tobias
   Norton, Rebecca
   Quail, Michael A.
   Sanders, Mandy
   Shanmugam, Dhanasekaran
   Sohal, Amandeep
   Wasmuth, James D.
   Brunk, Brian
   Grigg, Michael E.
   Howard, Jonathan C.
   Parkinson, John
   Roos, David S.
   Trees, Alexander J.
   Berriman, Matthew
   Pain, Arnab
   Wastling, Jonathan M.
TI Comparative Genomics of the Apicomplexan Parasites Toxoplasma gondii and
   Neospora caninum: Coccidia Differing in Host Range and Transmission
   Strategy
SO PLOS PATHOGENS
LA English
DT Article
ID PARASITOPHOROUS VACUOLE; MAXIMUM-LIKELIHOOD; SURFACE-ANTIGENS; CELL
   INVASION; RESISTANCE GTPASES; MOLECULAR CLOCK; GENE PREDICTION;
   DNA-SEQUENCES; EXPRESSION; VIRULENCE
AB Toxoplasma gondii is a zoonotic protozoan parasite which infects nearly one third of the human population and is found in an extraordinary range of vertebrate hosts. Its epidemiology depends heavily on horizontal transmission, especially between rodents and its definitive host, the cat. Neospora caninum is a recently discovered close relative of Toxoplasma, whose definitive host is the dog. Both species are tissue-dwelling Coccidia and members of the phylum Apicomplexa; they share many common features, but Neospora neither infects humans nor shares the same wide host range as Toxoplasma, rather it shows a striking preference for highly efficient vertical transmission in cattle. These species therefore provide a remarkable opportunity to investigate mechanisms of host restriction, transmission strategies, virulence and zoonotic potential. We sequenced the genome of N. caninum and transcriptomes of the invasive stage of both species, undertaking an extensive comparative genomics and transcriptomics analysis. We estimate that these organisms diverged from their common ancestor around 28 million years ago and find that both genomes and gene expression are remarkably conserved. However, in N. caninum we identified an unexpected expansion of surface antigen gene families and the divergence of secreted virulence factors, including rhoptry kinases. Specifically we show that the rhoptry kinase ROP18 is pseudogenised in N. caninum and that, as a possible consequence, Neospora is unable to phosphorylate host immunity-related GTPases, as Toxoplasma does. This defense strategy is thought to be key to virulence in Toxoplasma. We conclude that the ecological niches occupied by these species are influenced by a relatively small number of gene products which operate at the host-parasite interface and that the dominance of vertical transmission in N. caninum may be associated with the evolution of reduced virulence in this species.
C1 [Reid, Adam James; Cotton, James A.; Harris, David; Quail, Michael A.; Sanders, Mandy; Sohal, Amandeep; Berriman, Matthew; Pain, Arnab] Wellcome Trust Sanger Inst, Hinxton, Cambs, England.
   [Vermont, Sarah J.; Latham, Sophia M.; Norton, Rebecca; Trees, Alexander J.; Wastling, Jonathan M.] Univ Liverpool, Inst Infect & Global Hlth, Liverpool L69 3BX, Merseyside, England.
   [Vermont, Sarah J.; Latham, Sophia M.; Norton, Rebecca; Trees, Alexander J.; Wastling, Jonathan M.] Univ Liverpool, Sch Vet Sci, Fac Hlth & Life Sci, Liverpool L69 3BX, Merseyside, England.
   [Hill-Cawthorne, Grant A.; Pain, Arnab] King Abdullah Univ Sci & Technol, Jeddah, Saudi Arabia.
   [Koenen-Waisman, Stephanie; Howard, Jonathan C.] Univ Cologne, Inst Genet, Cologne, North Rhine Wes, Germany.
   [Mourier, Tobias] Univ Copenhagen, Nat Hist Museum Denmark, Ctr GeoGenet, Copenhagen, Denmark.
   [Shanmugam, Dhanasekaran; Brunk, Brian; Roos, David S.] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA.
   [Wasmuth, James D.; Parkinson, John] Univ Toronto, Hosp Sick Children, Program Mol Struct & Funct, Toronto, ON M5G 1X8, Canada.
   [Wasmuth, James D.; Parkinson, John] Univ Toronto, Dept Biochem, Toronto, ON M5G 1X8, Canada.
   [Wasmuth, James D.; Parkinson, John] Univ Toronto, Dept Mol Genet, Toronto, ON M5G 1X8, Canada.
   [Wasmuth, James D.; Grigg, Michael E.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Reid, AJ (reprint author), Wellcome Trust Sanger Inst, Hinxton, Cambs, England.
EM arnab.pain@kaust.edu.sa; j.wastling@liv.ac.uk
RI Hill-Cawthorne, Grant/B-8039-2009; Parkinson, John/A-4424-2008; Cotton,
   James/B-8806-2008; Mourier, Tobias/C-1164-2015; Pain, Arnab/L-5766-2015;
   
OI Hill-Cawthorne, Grant/0000-0002-3828-5473; Parkinson,
   John/0000-0001-9815-1189; Cotton, James/0000-0001-5475-3583; Mourier,
   Tobias/0000-0003-2727-1903; Pain, Arnab/0000-0002-1755-2819; Howard,
   Jonathan/0000-0003-2756-5143; Reid, Adam/0000-0002-5926-7768
FU BBSRC [BBS/B/08493]; Wellcome Trust [WT 085775/Z/08/Z]; Wellcome Trust
   Sanger Institute; German Research Foundation [SFB670, SFB680, SPP1399];
   CIHR [MOP84556]; Lundbeck Foundation
FX The work was funded by a BBSRC (http://www.bbsrc.ac.uk) grant
   BBS/B/08493 awarded to JMW and AJT with support from Wellcome Trust
   (http://www.wellcome.ac.uk) grant WT 085775/Z/08/Z. We also acknowledge
   the support of the Wellcome Trust Sanger Institute core sequencing and
   informatics groups. SKW and JCH were funded by SFB670, SFB680 and
   SPP1399 from the German Research Foundation (http://www.dfg.de). JP, MEG
   and JDW were funded by CIHR (#MOP84556; http://www.cihr-irsc.gc.ca). TM
   was funded by the Lundbeck Foundation (http://www.lundbeck.com). The
   funders had no role in study design, data collection and analysis,
   decision to publish, or preparation of the manuscript.
NR 93
TC 80
Z9 84
U1 1
U2 46
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7366
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAR
PY 2012
VL 8
IS 3
AR e1002567
DI 10.1371/journal.ppat.1002567
PG 15
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 918CC
UT WOS:000302225600021
PM 22457617
ER

PT J
AU Walther, M
   De Caul, A
   Aka, P
   Njie, M
   Amambua-Ngwa, A
   Walther, B
   Predazzi, IM
   Cunnington, A
   Deininger, S
   Takem, EN
   Ebonyi, A
   Weis, S
   Walton, R
   Rowland-Jones, S
   Sirugo, G
   Williams, SM
   Conway, DJ
AF Walther, Michael
   De Caul, Adam
   Aka, Peter
   Njie, Madi
   Amambua-Ngwa, Alfred
   Walther, Brigitte
   Predazzi, Irene M.
   Cunnington, Aubrey
   Deininger, Susanne
   Takem, Ebako N.
   Ebonyi, Augustine
   Weis, Sebastian
   Walton, Robert
   Rowland-Jones, Sarah
   Sirugo, Giorgio
   Williams, Scott M.
   Conway, David J.
TI HMOX1 Gene Promoter Alleles and High HO-1 Levels Are Associated with
   Severe Malaria in Gambian Children
SO PLOS PATHOGENS
LA English
DT Article
ID HEME OXYGENASE-1 GENE; PLASMODIUM-FALCIPARUM MALARIA; EXPERIMENTAL
   CEREBRAL MALARIA; RESPIRATORY-DISTRESS-SYNDROME; CRITICALLY-ILL
   PATIENTS; IRON CHELATION-THERAPY; MICROSATELLITE POLYMORPHISM;
   CARBON-MONOXIDE; OXIDATIVE STRESS; GLUCOSE-6-PHOSPHATE DEHYDROGENASE
AB Heme oxygenase 1 (HO-1) is an essential enzyme induced by heme and multiple stimuli associated with critical illness. In humans, polymorphisms in the HMOX1 gene promoter may influence the magnitude of HO-1 expression. In many diseases including murine malaria, HO-1 induction produces protective anti-inflammatory effects, but observations from patients suggest these may be limited to a narrow range of HO-1 induction, prompting us to investigate the role of HO-1 in malaria infection. In 307 Gambian children with either severe or uncomplicated P. falciparum malaria, we characterized the associations of HMOX1 promoter polymorphisms, HMOX1 mRNA inducibility, HO-1 protein levels in leucocytes (flow cytometry), and plasma (ELISA) with disease severity. The (GT)(n) repeat polymorphism in the HMOX1 promoter was associated with HMOX1 mRNA expression in white blood cells in vitro, and with severe disease and death, while high HO-1 levels were associated with severe disease. Neutrophils were the main HO-1-expressing cells in peripheral blood, and HMOX1 mRNA expression was upregulated by heme-moieties of lysed erythrocytes. We provide mechanistic evidence that induction of HMOX1 expression in neutrophils potentiates the respiratory burst, and propose this may be part of the causal pathway explaining the association between short (GT)(n) repeats and increased disease severity in malaria and other critical illnesses. Our findings suggest a genetic predisposition to higher levels of HO-1 is associated with severe illness, and enhances the neutrophil burst leading to oxidative damage of endothelial cells. These add important information to the discussion about possible therapeutic manipulation of HO-1 in critically ill patients.
C1 [Walther, Michael; De Caul, Adam; Aka, Peter; Njie, Madi; Amambua-Ngwa, Alfred; Walther, Brigitte; Cunnington, Aubrey; Deininger, Susanne; Takem, Ebako N.; Ebonyi, Augustine; Walton, Robert; Rowland-Jones, Sarah; Conway, David J.] MRC Labs, Banjul, Gambia.
   [Walther, Michael] NIAID, NIH, Rockville, MD USA.
   [Predazzi, Irene M.; Williams, Scott M.] Vanderbilt Univ Sch Med, Div Human Genom, Nashville, TN USA.
   [Predazzi, Irene M.; Williams, Scott M.] Ctr Human Genet Res, Nashville, TN USA.
   [Cunnington, Aubrey; Conway, David J.] London Sch Hyg & Trop Med, Fac Infect & Trop Dis, Dept Immunol & Infect, London WC1, England.
   [Deininger, Susanne] Univ Clin Bonn, Inst Med Microbiol Immunol & Parasitol, Bonn, Germany.
   [Weis, Sebastian] Univ Leipzig, Dept Internal Med Neurol & Dermatol, Leipzig, Germany.
   [Walton, Robert] Queen Mary Univ, Barts & London Sch Med & Dent, Inst Hlth Sci Educ, London, England.
   [Rowland-Jones, Sarah] John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DU, England.
   [Sirugo, Giorgio] Osped San Pietro FBF, Ctr Ric Sci, Ctr Genet, Rome, Italy.
RP Walther, M (reprint author), MRC Labs, Banjul, Gambia.
EM Michael.Walther@nih.gov
RI Williams, Scott/B-9491-2012; Weis, Sebastian/P-9016-2014; 
OI Weis, Sebastian/0000-0003-3201-2375; Conway, David/0000-0002-8711-3037;
   Cunnington, Aubrey/0000-0002-1305-3529; Walton,
   Robert/0000-0001-7700-1907
FU Medical Research Council (UK); NIH [2T32HL007751-16A2]
FX The work was funded by the Medical Research Council (UK). IMP was
   supported by NIH grant 2T32HL007751-16A2. The funders had no role in
   study design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
NR 101
TC 35
Z9 37
U1 1
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7366
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAR
PY 2012
VL 8
IS 3
AR e1002579
DI 10.1371/journal.ppat.1002579
PG 17
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 918CC
UT WOS:000302225600033
PM 22438807
ER

PT J
AU Brinton, LA
   Sahasrabuddhe, VV
   Scoccia, B
AF Brinton, Louise A.
   Sahasrabuddhe, Vikrant V.
   Scoccia, Bert
TI Fertility Drugs and the Risk of Breast and Gynecologic Cancers
SO SEMINARS IN REPRODUCTIVE MEDICINE
LA English
DT Article
DE infertility; ovulation-inducing drugs; cancer; risk
ID IN-VITRO FERTILIZATION; EPITHELIAL OVARIAN-CANCER; GRANULOSA-CELL TUMOR;
   HOSPITAL DISCHARGE DIAGNOSIS; OVULATION-STIMULATING DRUGS;
   POPULATION-BASED COHORT; STATES CASE-CONTROL; OF-THE-LITERATURE;
   INFERTILE WOMEN; UNITED-STATES
AB The evaluation of cancer risk among patients treated for infertility is complex, given the need to consider indications for use, treatment details, and the effects of other factors (including parity status) that independently affect cancer risk. Many studies have had methodologic limitations. Recent studies that have overcome some of these limitations have not confirmed a link between drug use and invasive ovarian cancers, although there is still a lingering question as to whether borderline tumors might be increased. It is unclear whether this merely reflects increased surveillance. Investigations regarding breast cancer risk have produced inconsistent results. In contrast, an increasing number of studies suggest that fertility drugs may have a special predisposition for the development of uterine cancers, of interest given that these tumors are recognized as particularly hormonally responsive. Additional studies are needed to clarify the effects on cancer risk of fertility drugs, especially those used in conjunction with in vitro fertilization. Because many women who have received such treatments are still relatively young, further monitoring should be pursued in large well-designed studies that enable assessment of effects within a variety of subgroups defined by both patient and disease characteristics.
C1 [Brinton, Louise A.; Sahasrabuddhe, Vikrant V.] NCI, Hormonal & Reprod Epidemiol Branch, Rockville, MD USA.
   [Scoccia, Bert] Univ Illinois, Coll Med, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Chicago, IL 60612 USA.
RP Brinton, LA (reprint author), 6120 Execut Blvd,Rm 5018, Rockville, MD 20852 USA.
EM brinton@nih.gov
RI Brinton, Louise/G-7486-2015
OI Brinton, Louise/0000-0003-3853-8562
FU NIH; National Cancer Institute
FX This manuscript was supported in part by the Intramural Research Program
   of the NIH and the National Cancer Institute.
NR 106
TC 16
Z9 16
U1 0
U2 5
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 1526-8004
J9 SEMIN REPROD MED
JI Semin. Reprod. Med.
PD MAR
PY 2012
VL 30
IS 2
BP 131
EP 145
DI 10.1055/s-0032-1307421
PG 15
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 920ZV
UT WOS:000302448700009
PM 22549713
ER

PT J
AU Olnes, MJ
   Poon, A
   Miranda, SJ
   Pfannes, L
   Tucker, Z
   Loeliger, K
   Padilla-Nash, H
   Yau, YY
   Ried, T
   Leitman, SF
   Young, NS
   Sloand, EM
AF Olnes, Matthew J.
   Poon, Andrea
   Miranda, Susan J.
   Pfannes, Loretta
   Tucker, Zachary
   Loeliger, Kelsey
   Padilla-Nash, Hesed
   Yau, Yu Ying
   Ried, Thomas
   Leitman, Susan F.
   Young, Neal S.
   Sloand, Elaine M.
TI Effects of granulocyte-colony-stimulating factor on Monosomy 7
   aneuploidy in healthy hematopoietic stem cell and granulocyte donors
SO TRANSFUSION
LA English
DT Article
ID APLASTIC-ANEMIA; G-CSF; CONGENITAL NEUTROPENIA; BREAST-CANCER; LEUKEMIA;
   BLOOD; RISK; CHEMOTHERAPY; THERAPY; TRIAL
AB BACKGROUND: Reports of Monosomy 7 in patients receiving granulocytecolony-stimulating factor (G-CSF) have raised concerns that this cytokine may promote genomic instability. However, there are no studies addressing whether repeated administration of G-CSF produces Monosomy 7 aneuploidy in healthy donors.
   STUDY DESIGN AND METHODS: We examined Chromosomes 7 and 8 by fluorescent in situ hybridization (FISH) in CD34+ cells from 35 healthy hematopoietic stem cell transplant (HSCT) donors after G-CSF administration for 5 days and by spectral karyotyping analysis (SKY) in four individuals to assess chromosomal integrity. We also studied 38 granulocyte donors who received up to 42 doses of G-CSF and dexamethasone (Dex) using FISH for Chromosomes 7 and 8.
   RESULTS: We found no abnormalities in Chromosomes 7 and 8 in G-CSF-mobilized CD34+ cells when assessed by FISH or SKY, nor did we detect aneuploidy in G-CSF- and Dex-treated donors.
   CONCLUSION: G-CSF does not promote clinically detectable Monosomy 7 or Trisomy 8 aneuploidy in HSCT or granulocyte donors. These findings should be reassuring to healthy HSCT and granulocyte donors.
C1 [Olnes, Matthew J.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
   Ctr Clin, Dept Transfus Med, Bethesda, MD USA.
   NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Olnes, MJ (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10 CRC 3-1341, Bethesda, MD 20892 USA.
EM olnesmj@nhlbi.nih.gov
FU NHLBI, NIH
FX Research supported by the intramuralo NHLBI, NIH.
NR 20
TC 6
Z9 6
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD MAR
PY 2012
VL 52
IS 3
BP 537
EP 541
DI 10.1111/j.1537-2995.2011.03313.x
PG 5
WC Hematology
SC Hematology
GA 904WI
UT WOS:000301229200014
PM 21883270
ER

PT J
AU Rodriguez, FJ
   Stratakis, CA
   Evans, DG
AF Rodriguez, Fausto J.
   Stratakis, Constantine A.
   Evans, D. Gareth
TI Genetic predisposition to peripheral nerve neoplasia: diagnostic
   criteria and pathogenesis of neurofibromatoses, Carney complex, and
   related syndromes
SO ACTA NEUROPATHOLOGICA
LA English
DT Review
DE Neurofibromatosis; NF1; NF2; Schwannomatosis; Carney complex; Multiple
   endocrine neoplasia; Neurofibroma; Schwannoma
ID PROTEIN-KINASE-A; SUBUNIT TYPE 1A; PSAMMOMATOUS MELANOTIC SCHWANNOMA;
   NODULAR ADRENOCORTICAL DISEASE; SPOTTY SKIN PIGMENTATION;
   PEUTZ-JEGHERS-SYNDROME; TUMOR-SUPPRESSOR GENE; OF-FUNCTION MUTATIONS;
   REGULATORY SUBUNIT; TYPE-2 NEUROFIBROMATOSIS
AB Neoplasms of the peripheral nerve sheath represent essential clinical manifestations of the syndromes known as the neurofibromatoses. Although involvement of multiple organ systems, including skin, central nervous system, and skeleton, may also be conspicuous, peripheral nerve neoplasia is often the most important and frequent cause of morbidity in these patients. Clinical characteristics of neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2) have been extensively described and studied during the last century, and the identification of mutations in the NF1 and NF2 genes by contemporary molecular techniques have created a separate multidisciplinary field in genetic medicine. In schwannomatosis, the most recent addition to the neurofibromatosis group, peripheral nervous system involvement is the exclusive (or almost exclusive) clinical manifestation. Although the majority of cases of schwannomatosis are sporadic, approximately one-third occur in families and a subset of these has recently been associated with germline mutations in the tumor suppressor gene SMARCB1/INI1. Other curious syndromes that involve the peripheral nervous system are associated with predominant endocrine manifestations, and include Carney complex and MEN2b, secondary to inactivating mutations in the PRKAR1A gene in a subset, and activating mutations in RET, respectively. In this review, we provide a concise update on the diagnostic criteria, pathology and molecular pathogenesis of these enigmatic syndromes in relation to peripheral nerve sheath neoplasia.
C1 [Rodriguez, Fausto J.] Johns Hopkins Univ, Div Neuropathol, Dept Pathol, Baltimore, MD 21205 USA.
   [Stratakis, Constantine A.] NICHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA.
   [Evans, D. Gareth] St Marys Hosp, Manchester Acad Hlth Sci Ctr, Dept Med Genet, Manchester M13 9WL, Lancs, England.
RP Rodriguez, FJ (reprint author), Johns Hopkins Univ, Div Neuropathol, Dept Pathol, 720 Rutland Ave,Ross Bldg,512B, Baltimore, MD 21205 USA.
EM frodrig4@jhmi.edu
OI Evans, Gareth/0000-0002-8482-5784
FU Intramural NIH HHS [ZIA HD008920-01]; NCI NIH HHS [P30 CA006973]
NR 125
TC 22
Z9 22
U1 1
U2 10
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0001-6322
EI 1432-0533
J9 ACTA NEUROPATHOL
JI Acta Neuropathol.
PD MAR
PY 2012
VL 123
IS 3
BP 349
EP 367
DI 10.1007/s00401-011-0935-7
PG 19
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 913EJ
UT WOS:000301856300004
PM 22210082
ER

PT J
AU Pinar, H
   Koch, MA
   Hawkins, H
   Heim-Hall, J
   Abramowsky, CR
   Thorsten, VR
   Carpenter, MW
   Zhou, HH
   Reddy, UM
AF Pinar, Halit
   Koch, Matthew A.
   Hawkins, Hal
   Heim-Hall, Josefine
   Abramowsky, Carlos R.
   Thorsten, Vanessa R.
   Carpenter, Marshall W.
   Zhou, Hong Holly
   Reddy, Uma M.
TI The Stillbirth Collaborative Research Network Postmortem Examination
   Protocol
SO AMERICAN JOURNAL OF PERINATOLOGY
LA English
DT Article
DE SCRN; postmortem examination; stillbirth; perinatal pathology
ID ACID OXIDATION DISORDERS; PERINATAL AUTOPSY; ORGAN WEIGHTS; DEATH;
   FETAL; SUDDEN; STANDARDS; FETUSES
AB After reviewing the state of knowledge about the scope and causes of stillbirth (SB) in a special workshop sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the participants determined that there is little guidance regarding the best use of postmortem examination (PM) to address the pathogenesis of stillbirth. In this report, we describe the PM procedure designed and used in the NICHD-supported Stillbirth Cooperative Research Network (SCRN). Perinatal pathologists, clinicians, epidemiologists, and biostatisticians at four tertiary care centers, a data coordinating center, and NICHD developed a standardized approach to perinatal PM, which was applied to a population-based study of stillbirth as part of the SCRN. The SCRN PM protocol was successfully instituted and used at the four medical centers. A total of 663 women with stillbirth were included: 620 delivered a single stillborn infant, 42 delivered twins, and one delivered triplets for a total of 676 stillborn infants. Of these women, 560 (84.5%) consented to PM (572 stillborn infants) that was conducted according to the SCRN protocol. A standardized PM protocol was developed to evaluate stillbirth consistently across centers in the United States. Novel testing and approaches that increase the yield of the PM can be developed using this model.
C1 [Pinar, Halit] Brown Univ, Women & Infants Hosp, Alpert Sch Med, Div Perinatal Pathol, Providence, RI 02905 USA.
   [Koch, Matthew A.] RTI Int, Dept Stat & Epidemiol, Res Triangle Pk, NC USA.
   [Hawkins, Hal] UTMB Galveston, Dept Pediat Pathol, Galveston, TX USA.
   [Heim-Hall, Josefine] UTHSC, San Antonio Sch Med, San Antonio, TX USA.
   [Abramowsky, Carlos R.] Egleston Hosp, Pathol Lab, Atlanta, GA USA.
   [Thorsten, Vanessa R.] RTI Int, Dept Stat & Data Anal, Kansas City, MO USA.
   [Carpenter, Marshall W.] Tufts Univ, Sch Med, Dept Maternal & Fetal Med, Boston, MA 02111 USA.
   [Zhou, Hong Holly] Primary Childrens Med Ctr, Dept Pediat Pathol, Salt Lake City, UT 84103 USA.
   [Reddy, Uma M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Pinar, H (reprint author), Brown Univ, Women & Infants Hosp, Alpert Sch Med, Div Perinatal Pathol, 101 Dudley St, Providence, RI 02905 USA.
EM halit.pinar@gmail.com
FU Stillbirth Collaborative Research Network (Brown University, Rhode
   Island) [U10-HD045953]; Stillbirth Collaborative Research Network (Emory
   University, Georgia) [U10-HD045925]; Stillbirth Collaborative Research
   Network (University of Texas Medical Branch at Galveston, Texas)
   [U10-HD045952]; Stillbirth Collaborative Research Network (University of
   Texas Health Science Center at San Antonio, Texas) [U10-HD045955];
   Stillbirth Collaborative Research Network (University of Utah Health
   Sciences Center, Utah) [U10-HD045944]; Stillbirth Collaborative Research
   Network (RTI International, North Carolina) [U01-HD-45954]; Eunice
   Kennedy Shriver National Institute of Child Health and Human Development
FX Supported in part by grant funding from the Stillbirth Collaborative
   Research Network sites: U10-HD045953 (Brown University, Rhode Island);
   U10-HD045925 (Emory University, Georgia); U10-HD045952 (University of
   Texas Medical Branch at Galveston, Texas); U10-HD045955 (University of
   Texas Health Science Center at San Antonio, Texas); U10-HD045944
   (University of Utah Health Sciences Center, Utah); and U01-HD-45954 (RTI
   International, North Carolina); and by funding from the Eunice Kennedy
   Shriver National Institute of Child Health and Human Development.
NR 40
TC 16
Z9 16
U1 1
U2 2
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0735-1631
J9 AM J PERINAT
JI Am. J. Perinatol.
PD MAR
PY 2012
VL 29
IS 3
BP 187
EP 202
DI 10.1055/s-0031-1284228
PG 16
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 916PH
UT WOS:000302115200005
PM 21815127
ER

PT J
AU Zabaneh, R
   Smith, LM
   LaGasse, LL
   Derauf, C
   Newman, E
   Shah, R
   Arria, A
   Huestis, M
   Haning, W
   Strauss, A
   Della Grotta, S
   Dansereau, LM
   Lin, H
   Neal, C
   Lester, BM
AF Zabaneh, Rachel
   Smith, Lynne M.
   LaGasse, Linda L.
   Derauf, Chris
   Newman, Elana
   Shah, Rizwan
   Arria, Amelia
   Huestis, Marilyn
   Haning, William
   Strauss, Arthur
   Della Grotta, Sheri
   Dansereau, Lynne M.
   Lin, Hai
   Neal, Charles
   Lester, Barry M.
TI The Effects of Prenatal Methamphetamine Exposure on Childhood Growth
   Patterns from Birth to 3 Years of Age
SO AMERICAN JOURNAL OF PERINATOLOGY
LA English
DT Article
DE height; antenatal; drug; amphetamine
ID INFANT DEVELOPMENT; LIFE-STYLE; INTRAUTERINE GROWTH; FETAL-GROWTH;
   CHILDREN; ENVIRONMENT; DRUGS; PREGNANCY; ALCOHOL; COCAINE
AB We examined the effects of prenatal methamphetamine (MA) exposure on growth parameters from birth to age 3 years. The 412 subjects included (n = 204 exposed) were enrolled at birth in the Infant Development, Environment and Lifestyle study, a longitudinal study assessing the effects of prenatal MA exposure on childhood outcomes. Individual models were used to examine the effects of prenatal MA exposure on weight, head circumference, height, and weight-for-length growth trajectories. After adjusting for covariates, height trajectory was lower in the exposed versus the comparison children (p = 0.021) over the first 3 years of life. Both groups increased height on average by 2.27 cm per month by age 3 years. In term subjects, MA exposure was also associated with a lower height trajectory (p = 0.034), with both the exposed and comparison groups gaining 2.25 cm per month by age 3 years. There was no difference in weight, head circumference, or weight-for-length growth trajectories between the comparison and the exposed groups. Children exposed prenatally to MA have a modest decrease in height growth trajectory during the first 3 years of life with no observed difference in weight, head circumference, or weight-for-length trajectories.
C1 [Zabaneh, Rachel; Smith, Lynne M.] Harbor UCLA Med Ctr, Los Angeles Biomed Inst, Los Angeles, CA USA.
   [Zabaneh, Rachel; Smith, Lynne M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
   [LaGasse, Linda L.; Della Grotta, Sheri; Dansereau, Lynne M.; Lin, Hai; Lester, Barry M.] Brown Univ, Women & Infants Hosp, Warren Alpert Med Sch, Ctr Study Children Risk, Providence, RI USA.
   [Derauf, Chris; Haning, William; Neal, Charles] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA.
   [Newman, Elana] Univ Tulsa, Dept Psychol, Tulsa, OK 74104 USA.
   [Shah, Rizwan] Blank Hosp Reg Child Protect Ctr Iowa Hlth, Des Moines, IA USA.
   [Arria, Amelia] Univ Maryland, Ctr Substance Abuse Res CESAR, College Pk, MD 20742 USA.
   [Huestis, Marilyn] NIDA, Intramural Res Program, NIH, Baltimore, MD USA.
   [Strauss, Arthur] Long Beach Mem Med Ctr, Long Beach, CA USA.
RP Smith, LM (reprint author), Harbor UCLA Med Ctr, Los Angeles Biomed Inst, 1124 W Carson St,Box 446, Torrance, CA 90502 USA.
EM smith@labiomed.org
OI Arria, Amelia/0000-0002-6360-9265
FU National Institute on Drug Abuse (NIDA) [R01DA014948]; National Center
   on Research Resources [3 M01 RR00425, P20 RR11091]
FX This study is part of the Infant Development, Environment and Lifestyle
   (IDEAL) Study, which was conducted with support from the National
   Institute on Drug Abuse (NIDA), R01DA014948 (Barry Lester, Ph.D.) and in
   part by the National Center on Research Resources, Grant # 3 M01 RR00425
   and P20 RR11091.
NR 39
TC 9
Z9 9
U1 0
U2 6
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0735-1631
J9 AM J PERINAT
JI Am. J. Perinatol.
PD MAR
PY 2012
VL 29
IS 3
BP 203
EP 210
DI 10.1055/s-0031-1285094
PG 8
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 916PH
UT WOS:000302115200006
PM 21818727
ER

PT J
AU Dizon-Townson, D
   Miller, C
   Momirova, V
   Sibai, B
   Spong, CY
   Wendel, G
   Wenstrom, K
   Samuels, P
   Caritis, S
   Sorokin, Y
   Miodovnik, M
   O'Sullivan, MJ
   Conway, D
   Wapner, RJ
   Gabbe, SG
AF Dizon-Townson, Donna
   Miller, Connie
   Momirova, Valerija
   Sibai, Baha
   Spong, Catherine Y.
   Wendel, George, Jr.
   Wenstrom, Katharine
   Samuels, Philip
   Caritis, Steve
   Sorokin, Yoram
   Miodovnik, Menachem
   O'Sullivan, Mary J.
   Conway, Deborah
   Wapner, Ronald J.
   Gabbe, Steven G.
TI Impact of Smoking during Pregnancy on Functional Coagulation Testing
SO AMERICAN JOURNAL OF PERINATOLOGY
LA English
DT Article
DE coagulation; smoking; pregnancy; factor V Leiden
ID RISK-FACTORS; WOMEN; OUTCOMES
AB Compounds that are systemically absorbed during the course of cigarette smoking, and their metabolites, affect the coagulation system and cause endothelial dysfunction, dyslipidemia, and platelet activation leading to a prothrombotic state. In addition, smoking increases the activity of fibrinogen, homocysteine, and C-reactive protein. We hypothesize that smoking may affect functional coagulation testing during pregnancy. A secondary analysis of 371 women pregnant with a singleton pregnancy and enrolled in a multicenter, prospective observational study of complications of factor V Leiden mutation subsequently underwent functional coagulation testing for antithrombin III, protein C antigen and activity, and protein S antigen and activity. Smoking was assessed by self-report at time of enrollment (< 14 weeks). None of the functional coagulation testing results was altered by maternal smoking during pregnancy. Smoking does not affect the aforementioned functional coagulation testing results during pregnancy.
C1 [Dizon-Townson, Donna] Univ Utah, Hlth Sci Ctr, Dept Obstet & Gynecol, Salt Lake City, UT 84132 USA.
   [Miller, Connie] Ctr Dis Control & Prevent, Hemostasis Lab, Atlanta, GA USA.
   [Momirova, Valerija] George Washington Univ, Biostat Coordinating Ctr, Washington, DC USA.
   [Sibai, Baha; Miodovnik, Menachem] Univ Cincinnati, Dept Obstet & Gynecol, Cincinnati, OH USA.
   [Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, Bethesda, MD USA.
   [Wendel, George, Jr.] Univ Texas SW, Dept Obstet & Gynecol, Dallas, TX USA.
   [Wenstrom, Katharine] Brown Univ, Providence, RI 02912 USA.
   [Wenstrom, Katharine] Women & Infants Hosp Rhode Isl, Providence, RI 02908 USA.
   [Samuels, Philip; Gabbe, Steven G.] Ohio State Univ, Columbus, OH 43210 USA.
   [Caritis, Steve] Magee Womens Res Inst, Dept Maternal Fetal Med, Pittsburgh, PA USA.
   [O'Sullivan, Mary J.] Univ Texas San Antonio, Hlth Sci Ctr, Dept Obstet & Gynecol, San Antonio, TX 78284 USA.
   [O'Sullivan, Mary J.] Univ Miami, Coral Gables, FL 33124 USA.
   [Conway, Deborah] UT Hlth Sci Ctr San Antonio, Sch Med, San Antonio, TX USA.
   [Wapner, Ronald J.] Columbia Univ, New York, NY USA.
   [Sorokin, Yoram] Wayne State Univ, Sch Med, Div Maternal Fetal Med, Detroit, MI USA.
   [Sorokin, Yoram] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA.
RP Dizon-Townson, D (reprint author), Univ Utah, Hlth Sci Ctr, Dept Obstet & Gynecol, 50 N Med Dr,Room 2B200, Salt Lake City, UT 84132 USA.
EM donna.dizon-townson@imail.org
RI Samuels, Philip/E-4011-2011; 
OI caritis, steve/0000-0002-2169-0712; Miller, Connie H/0000-0002-3989-7973
FU Eunice Kennedy Shriver National Institute of Child Health and Human
   Development [HD27869, HD21414, U01-HD36801, HD34208, HD27860, HD34116,
   HD34136, HD27861, HD34122, HD21410, HD27915, HD34210, HD27905, HD27917];
   National Institutes of Health Office of Research on Women's Health
FX This work was supported by the Eunice Kennedy Shriver National Institute
   of Child Health and Human Development (HD27869, HD21414, U01-HD36801,
   HD34208, HD27860, HD34116, HD34136, HD27861, HD34122, HD21410, HD27915,
   HD34210, HD27905, and HD27917) and the National Institutes of Health
   Office of Research on Women's Health
NR 19
TC 0
Z9 0
U1 0
U2 1
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0735-1631
J9 AM J PERINAT
JI Am. J. Perinatol.
PD MAR
PY 2012
VL 29
IS 3
BP 225
EP 229
DI 10.1055/s-0031-1285097
PG 5
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 916PH
UT WOS:000302115200009
PM 21818732
ER

PT J
AU Klabunde, CN
   Marcus, PM
   Han, PKJ
   Richards, TB
   Vernon, SW
   Yuan, GG
   Silvestri, GA
AF Klabunde, Carrie N.
   Marcus, Pamela M.
   Han, Paul K. J.
   Richards, Thomas B.
   Vernon, Sally W.
   Yuan, Gigi
   Silvestri, Gerard A.
TI Lung Cancer Screening Practices of Primary Care Physicians: Results From
   a National Survey
SO ANNALS OF FAMILY MEDICINE
LA English
DT Article
DE lung cancer; screening; primary care; physicians; physician's practice
   patterns
ID COMPUTED-TOMOGRAPHY; SOCIETY GUIDELINES; FAMILY PHYSICIANS;
   CLINICAL-PRACTICE; UNITED-STATES; MORTALITY; TESTS; TRIAL
AB PURPOSE Although current practice guidelines do not recommend screening asymptomatic patients for lung cancer, physicians may still order lung cancer screening tests. No recent national survey of health care professionals has focused on lung cancer screening. In this study, we examined the lung cancer screening practices of US primary care physicians and characteristics of those who order lung cancer screening tests.
   METHODS We conducted a nationally representative survey of practicing primary care physicians in 2006-2007. Mailed questionnaires assessed the physicians' knowledge of lung cancer screening guidelines, beliefs about the effectiveness of screening tests, and ordering of screening chest radiograph, low-dose spiral computed tomography, or sputum cytology in the past 12 months. Clinical vignettes were used to assess the physicians' intentions to screen asymptomatic 50-year-old patients with varying smoking histories for lung cancer.
   RESULTS A total of 962 family physicians, general practitioners, and general internists completed questionnaires (cooperation rate = 76.8%). Overall, 38% had ordered no lung cancer screening tests; 55% had ordered chest radiograph, 22% low-dose spiral computed tomography, and less than 5% sputum cytology. In multivariate modeling, physicians were more likely to have ordered lung cancer screening tests if they believed that expert groups recommend lung cancer screening or that screening tests are effective; if they would recommend screening for asymptomatic patients, including patients without substantial smoking exposure; and if their patients had asked them about screening.
   CONCLUSIONS Primary care physicians in the United States frequently order lung cancer screening tests for asymptomatic patients, even though expert groups do not recommend it. Primary care physicians and patients need more information about lung cancer screening's evidence base, guidelines, potential harms, and costs to avert inappropriate ordering.
C1 [Klabunde, Carrie N.; Marcus, Pamela M.] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
   [Han, Paul K. J.] Maine Med Ctr, Ctr Outcomes Res & Evaluat, Portland, ME 04102 USA.
   [Richards, Thomas B.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA.
   [Vernon, Sally W.] Univ Texas Houston, Sch Publ Hlth, Div Hlth Promot & Behav Sci, Houston, TX USA.
   [Yuan, Gigi] Informat Management Serv Inc, Silver Spring, MD USA.
   [Silvestri, Gerard A.] Med Univ S Carolina, Div Pulm & Crit Care Med, Charleston, SC 29425 USA.
RP Klabunde, CN (reprint author), NCI, Appl Res Program, Div Canc Control & Populat Sci, EPN 4005,6130 Execut Blvd, Bethesda, MD 20892 USA.
EM KlabundC@mail.nih.gov
OI Han, Paul/0000-0003-0165-1940
FU National Cancer Institute [N02-PC-51308, R01 CA112223, K24 CA120494-2];
   Agency for Healthcare Research and Quality [Y3-PC-5019-01,
   Y3-PC-5019-02]; Centers for Disease Control and Prevention
   [Y3-PC-6017-01]; Department of Defense [W81XWH-05-1-0378]
FX Funding support for the study was provided by the National Cancer
   Institute (contract N02-PC-51308), the Agency for Healthcare Research
   and Quality (interagency agreements Y3-PC-5019-01 and Y3-PC-5019-02),
   and the Centers for Disease Control and Prevention (interagency
   agreement Y3-PC-6017-01). In addition, Dr Vernon is supported by NCI
   grant R01 CA112223, and Dr Silvestri by an NCI investigator grant in
   patient-oriented research (K24 CA120494-2) and a Department of Defense
   grant in computer-aided cancer management (W81XWH-05-1-0378).
NR 42
TC 15
Z9 16
U1 0
U2 7
PU ANNALS FAMILY MEDICINE
PI LEAWOOD
PA 11400 TOMAHAWK CREEK PARKWAY, LEAWOOD, KS 66211-2672 USA
SN 1544-1709
J9 ANN FAM MED
JI Ann. Fam. Med.
PD MAR-APR
PY 2012
VL 10
IS 2
BP 102
EP 110
DI 10.1370/afm.1340
PG 9
WC Primary Health Care; Medicine, General & Internal
SC General & Internal Medicine
GA 915AX
UT WOS:000301996400003
PM 22412001
ER

PT J
AU Yates, JW
   Thein, M
   Ershler, WB
AF Yates, Jerome W.
   Thein, Mya
   Ershler, William B.
TI Opinion on opinions about geriatric assessment
SO ARCHIVES OF GERONTOLOGY AND GERIATRICS
LA English
DT Editorial Material
ID RANDOMIZED CONTROLLED-TRIAL; CONTROLLED CLINICAL-TRIAL; PREVENTIVE HOME
   VISITS; CONGESTIVE-HEART-FAILURE; DWELLING OLDER-ADULTS; ELDERLY-PEOPLE;
   ACUTE-CARE; CONSULTATION TEAM; HOSPITALIZED-PATIENTS; FUNCTIONAL DECLINE
C1 [Yates, Jerome W.; Thein, Mya; Ershler, William B.] NIA, Translat Res Sect, Clin Res Branch, Intramural Res Program, Bethesda, MD 20892 USA.
RP Ershler, WB (reprint author), Inst Adv Studies Aging, 15952 Shady Grove Rd, Gaithersburg, MD 20877 USA.
EM wershler@iasia.org
FU Intramural NIH HHS
NR 81
TC 3
Z9 3
U1 7
U2 9
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0167-4943
J9 ARCH GERONTOL GERIAT
JI Arch. Gerontol. Geriatr.
PD MAR-APR
PY 2012
VL 54
IS 2
BP 273
EP 277
DI 10.1016/j.archger.2011.07.007
PG 5
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 910NV
UT WOS:000301647400043
PM 21978413
ER

PT J
AU Wu, Y
   Lousberg, EL
   Moldenhauer, LM
   Hayball, JD
   Coller, JK
   Rice, KC
   Watkins, LR
   Somogyi, AA
   Hutchinson, MR
AF Wu, Yue
   Lousberg, Erin L.
   Moldenhauer, Lachlan M.
   Hayball, John D.
   Coller, Janet K.
   Rice, Kenner C.
   Watkins, Linda R.
   Somogyi, Andrew A.
   Hutchinson, Mark R.
TI Inhibiting the TLR4-MyD88 signalling cascade by genetic or
   pharmacological strategies reduces acute alcohol-induced sedation and
   motor impairment in mice
SO BRITISH JOURNAL OF PHARMACOLOGY
LA English
DT Article
DE alcohol; TLR4; MyD88; I?Ba; loss of righting reflex; sedation; motor
   impairment; mice studies
ID NF-KAPPA-B; ETHANOL-INDUCED ACTIVATION; GABAERGIC TRANSMISSION;
   INFLAMMATORY MEDIATORS; CULTURED ASTROCYTES; ASTROGLIAL CELLS; BRAIN;
   EXPRESSION; RECEPTORS; TLR4
AB BACKGROUND AND PURPOSE
   Emerging evidence implicates a role for toll-like receptor 4 (TLR4) in the CNS effects of alcohol. The aim of the current study was to determine whether TLR4MyD88-dependent signalling is involved in the acute behavioural actions of alcohol and if alcohol can activate TLR4-downstream MAPK and NF-kappa B pathways.
   EXPERIMENTAL APPROACH
   The TLR4 pathway was evaluated using the TLR4 antagonist (+)-naloxone (m-opioid receptor-inactive isomer) and mice with null mutations in the TLR4 and MyD88 genes. Sedation and motor impairment induced by a single dose of alcohol were assessed by loss of righting reflex (LORR) and rotarod tests, separately. The phosphorylation of JNK, ERK and p38, and levels of I kappa B alpha were measured to determine the effects of acute alcohol exposure on MAPK and NF-kappa B signalling.
   KEY RESULTS
   After a single dose of alcohol, both pharmacological inhibition of TLR4 signalling with (+)-naloxone and genetic deficiency of TLR4 or MyD88 significantly (P < 0.0001) reduced the duration of LORR by 45-78% and significantly decreased motor impairment recovery time to 62-88% of controls. These behavioural actions were not due to changes in the peripheral or central alcohol pharmacokinetics. I kappa B alpha levels responded to alcohol by 30 min in mixed hippocampal cell samples, from wild-type mice, but not in cells from TLR4-or MyD88-deficient mice.
   CONCLUSIONS AND IMPLICATIONS These data provide new evidence that TLR4-MyD88 signalling is involved in the acute behavioural actions of alcohol in mice.
C1 [Wu, Yue; Coller, Janet K.; Somogyi, Andrew A.; Hutchinson, Mark R.] Univ Adelaide, Sch Med Sci, Discipline Physiol, Adelaide, SA, Australia.
   [Lousberg, Erin L.; Hayball, John D.] SA Pathol, Hanson Inst, Adelaide, SA, Australia.
   [Lousberg, Erin L.; Hayball, John D.] Univ S Australia, Sch Pharm & Med Sci, Sansom Inst, Adelaide, SA 5001, Australia.
   [Moldenhauer, Lachlan M.] Univ Adelaide, Sch Paediat & Reprod Hlth, Res Ctr Reprod Hlth, Adelaide, SA, Australia.
   [Hayball, John D.] Univ Adelaide, Sch Med, Adelaide, SA, Australia.
   [Rice, Kenner C.] Natl Inst Drug Abuse, Chem Biol Res Branch, Rockville, MD USA.
   [Rice, Kenner C.] NIAAA, NIH, Rockville, MD 20852 USA.
   [Watkins, Linda R.] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA.
   [Watkins, Linda R.] Univ Colorado, Ctr Neurosci, Boulder, CO 80309 USA.
RP Hutchinson, MR (reprint author), Univ Adelaide, Sch Med Sci, Discipline Physiol, Adelaide, SA, Australia.
EM mark.hutchinson@adelaide.edu.au
RI Hayball, John/F-4137-2013; Hutchinson, Mark/G-4147-2014
OI Hayball, John/0000-0002-3089-4506; Hutchinson, Mark/0000-0003-2154-5950
FU China Scholarship Council (CSC)-University of Adelaide; Cancer Council
   of South Australia; NIH of NIDA; NIH of NIAAA; NHMRC
FX YW is the recipient of China Scholarship Council (CSC)-University of
   Adelaide Joint Postgraduate Scholarship. MRH is a NHMRC CJ Martin Fellow
   (ID 465423; 2007-2010) and an Australian Research Council Research
   Fellow (DP110100297). JKC is a FTT Fricker Research Fellow (Medical
   Endowment Funds), Faculty of Health Sciences, University of Adelaide. EL
   was supported by the Cancer Council of South Australia through provision
   of a PhD stipend. The authors thank Prof Sarah Robertson for her
   technical assistance on flow cytometry and helpful comments on the
   manuscript and the reviewers for constructive suggestions. This work was
   partially supported by the NIH Intramural Research Programs of NIDA and
   NIAAA and NHMRC.
NR 54
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Z9 35
U1 0
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-1188
J9 BRIT J PHARMACOL
JI Br. J. Pharmacol.
PD MAR
PY 2012
VL 165
IS 5
BP 1319
EP 1329
DI 10.1111/j.1476-5381.2011.01572.x
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 894SZ
UT WOS:000300448500010
PM 21955045
ER

PT J
AU Bashashati, M
   Storr, MA
   Nikas, SP
   Wood, JT
   Godlewski, G
   Liu, J
   Ho, W
   Keenan, CM
   Zhang, H
   Alapafuja, SO
   Cravatt, BF
   Lutz, B
   Mackie, K
   Kunos, G
   Patel, KD
   Makriyannis, A
   Davison, JS
   Sharkey, KA
AF Bashashati, M.
   Storr, M. A.
   Nikas, S. P.
   Wood, J. T.
   Godlewski, G.
   Liu, J.
   Ho, W.
   Keenan, C. M.
   Zhang, H.
   Alapafuja, S. O.
   Cravatt, B. F.
   Lutz, B.
   Mackie, K.
   Kunos, G.
   Patel, K. D.
   Makriyannis, A.
   Davison, J. S.
   Sharkey, K. A.
TI Inhibiting fatty acid amide hydrolase normalizes endotoxin-induced
   enhanced gastrointestinal motility in mice
SO BRITISH JOURNAL OF PHARMACOLOGY
LA English
DT Article
DE endocannabinoids; gastrointestinal motility; lipopolysaccharide; fatty
   acid amide hydrolase; cannabinoid receptors
ID ENTERIC NERVOUS-SYSTEM; LIPOPOLYSACCHARIDE-TREATED RATS; ENDOCANNABINOID
   SYSTEM; CANNABINOID RECEPTOR; MOUSE COLON; ANANDAMIDE HYDROLYSIS;
   EXPERIMENTAL COLITIS; OXIDATIVE STRESS; CB1 RECEPTORS; INFLAMMATION
AB BACKGROUND AND PURPOSE
   Gastrointestinal (GI) motility is regulated in part by fatty acid ethanolamides (FAEs), including the endocannabinoid (EC) anandamide (AEA). The actions of FAEs are terminated by fatty acid amide hydrolase (FAAH). We investigated the actions of the novel FAAH inhibitor AM3506 on normal and enhanced GI motility.
   EXPERIMENTAL APPROACH
   We examined the effect of AM3506 on electrically-evoked contractility in vitro and GI transit and colonic faecal output in vivo, in normal and FAAH-deficient mice treated with saline or LPS (100 mg.kg(-1), i. p.), in the presence and absence of cannabinoid (CB) receptor antagonists. mRNA expression was measured by quantitative real time-PCR, EC levels by liquid chromatography-MS and FAAH activity by the conversion of [H-3]-AEA to [3H]-ethanolamine in intestinal extracts. FAAH expression was examined by immunohistochemistry.
   KEY RESULTS
   FAAH was dominantly expressed in the enteric nervous system; its mRNA levels were higher in the ileum than the colon. LPS enhanced ileal contractility in the absence of overt inflammation. AM3506 reversed the enhanced electrically-evoked contractions of the ileum through CB1 and CB2 receptors. LPS increased the rate of upper GI transit and faecal output. AM3506 normalized the enhanced GI transit through CB1 and CB2 receptors and faecal output through CB1 receptors. LPS did not increase GI transit in FAAH-deficient mice.
   CONCLUSIONS AND IMPLICATIONS
   Inhibiting FAAH normalizes various parameters of GI dysmotility in intestinal pathophysiology. Inhibition of FAAH represents a new approach to the treatment of disordered intestinal motility.
C1 [Bashashati, M.; Ho, W.; Keenan, C. M.; Zhang, H.; Patel, K. D.; Davison, J. S.; Sharkey, K. A.] Univ Calgary, Dept Physiol & Pharmacol, Hotchkiss Brain Inst, Calgary, AB T2N 4N1, Canada.
   [Bashashati, M.; Ho, W.; Keenan, C. M.; Zhang, H.; Patel, K. D.; Davison, J. S.; Sharkey, K. A.] Univ Calgary, Dept Physiol & Pharmacol, Snyder Inst Infect Immun & Inflammat, Calgary, AB T2N 4N1, Canada.
   [Storr, M. A.] Univ Calgary, Snyder Inst Infect Immun & Inflammat, Div Gastroenterol, Dept Med, Calgary, AB T2N 4N1, Canada.
   [Nikas, S. P.; Wood, J. T.; Alapafuja, S. O.; Makriyannis, A.] Northeastern Univ, Ctr Drug Discovery, Boston, MA 02115 USA.
   [Godlewski, G.; Liu, J.; Kunos, G.] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD USA.
   [Cravatt, B. F.] Scripps Res Inst, La Jolla, CA 92037 USA.
   [Lutz, B.] Johannes Gutenberg Univ Mainz, Inst Physiol Chem, Univ Med Ctr, Mainz, Germany.
   [Mackie, K.] Indiana Univ, Gill Ctr Biomol Sci, Dept Psychol & Brain Sci, Bloomington, IN USA.
RP Sharkey, KA (reprint author), Univ Calgary, Dept Physiol & Pharmacol, Hotchkiss Brain Inst, 3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada.
EM ksharkey@ucalgary.ca
RI Mackie, Ken/E-3715-2013
OI Mackie, Ken/0000-0001-8501-6199
FU Canadian Institutes of Health Research; National Institutes of Health
   (NIH) [DA09158, DA7215, DA3801, DA023142, DA11322, DA21696]; University
   of Calgary Research Grant Committee
FX Grant Support: This work was supported by grants from the Canadian
   Institutes of Health Research (to KAS, KDP and JSD) and National
   Institutes of Health (NIH; grants DA09158, DA7215, DA3801 and DA023142
   to AM). MAS was supported by the University of Calgary Research Grant
   Committee. KM was supported by NIH grants DA11322 and DA21696. KAS and
   KDP are Alberta Heritage Foundation for Medical Research Medical
   Scientists. KDP holds a Canada Research Chair. KAS holds the CCFC Chair
   in IBD Research at University of Calgary.
NR 68
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U1 1
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-1188
J9 BRIT J PHARMACOL
JI Br. J. Pharmacol.
PD MAR
PY 2012
VL 165
IS 5
BP 1556
EP 1571
DI 10.1111/j.1476-5381.2011.01644.x
PG 16
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 894SZ
UT WOS:000300448500029
PM 21883147
ER

PT J
AU Linet, MS
   Slovis, TL
   Miller, DL
   Kleinerman, R
   Lee, C
   Rajaraman, P
   de Gonzalez, AB
AF Linet, Martha S.
   Slovis, Thomas L.
   Miller, Donald L.
   Kleinerman, Ruth
   Lee, Choonsik
   Rajaraman, Preetha
   de Gonzalez, Amy Berrington
TI Cancer risks associated with external radiation from diagnostic imaging
   procedures
SO CA-A CANCER JOURNAL FOR CLINICIANS
LA English
DT Review
ID US RADIOLOGIC TECHNOLOGISTS; ATOMIC-BOMB SURVIVORS; DNA-REPAIR GENES;
   CARDIAC COMPUTED-TOMOGRAPHY; TECHA RIVER COHORT; X-RAY-EXPOSURE;
   CARDIOVASCULAR-MAGNETIC-RESONANCE; ACUTE LYMPHOBLASTIC-LEUKEMIA;
   NORTH-AMERICAN-SOCIETY; LI-FRAUMENI-SYNDROME
AB The 600% increase in medical radiation exposure to the US population since 1980 has provided immense benefit, but increased potential future cancer risks to patients. Most of the increase is from diagnostic radiologic procedures. The objectives of this review are to summarize epidemiologic data on cancer risks associated with diagnostic procedures, describe how exposures from recent diagnostic procedures relate to radiation levels linked with cancer occurrence, and propose a framework of strategies to reduce radiation from diagnostic imaging in patients. We briefly review radiation dose definitions, mechanisms of radiation carcinogenesis, key epidemiologic studies of medical and other radiation sources and cancer risks, and dose trends from diagnostic procedures. We describe cancer risks from experimental studies, future projected risks from current imaging procedures, and the potential for higher risks in genetically susceptible populations. To reduce future projected cancers from diagnostic procedures, we advocate the widespread use of evidence-based appropriateness criteria for decisions about imaging procedures; oversight of equipment to deliver reliably the minimum radiation required to attain clinical objectives; development of electronic lifetime records of imaging procedures for patients and their physicians; and commitment by medical training programs, professional societies, and radiation protection organizations to educate all stakeholders in reducing radiation from diagnostic procedures. CA Cancer J Clin 2012. (C) 2012 American Cancer Society.
C1 [Linet, Martha S.; Kleinerman, Ruth; Lee, Choonsik; Rajaraman, Preetha; de Gonzalez, Amy Berrington] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Slovis, Thomas L.] Childrens Hosp Michigan, Dept Radiol, Detroit, MI 48201 USA.
   [Miller, Donald L.] US FDA, Diagnost Devices Branch, Div Mammog Qual, Silver Spring, MD USA.
   [Miller, Donald L.] US FDA, Radiat Program Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
RP Linet, MS (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 7048, Bethesda, MD 20892 USA.
EM linetm@mail.nih.gov
RI Lee, Choonsik/C-9023-2015; 
OI Lee, Choonsik/0000-0003-4289-9870; Kleinerman, Ruth/0000-0001-7415-2478
FU National Institutes of Health; National Cancer Institute
FX This review was supported by the Intramural Research Program of the
   National Institutes of Health and the National Cancer Institute.
NR 239
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U1 4
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-9235
EI 1542-4863
J9 CA-CANCER J CLIN
JI CA-Cancer J. Clin.
PD MAR-APR
PY 2012
VL 62
IS 2
BP 75
EP 100
DI 10.3322/caac.21132
PG 26
WC Oncology
SC Oncology
GA 904VW
UT WOS:000301227600003
PM 22307864
ER

PT J
AU Aflaki, E
   Doddapattar, P
   Radovic, B
   Povoden, S
   Kolb, D
   Vujic, N
   Wegscheider, M
   Koefeler, H
   Hornemann, T
   Graier, WF
   Malli, R
   Madeo, F
   Kratky, D
AF Aflaki, E.
   Doddapattar, P.
   Radovic, B.
   Povoden, S.
   Kolb, D.
   Vujic, N.
   Wegscheider, M.
   Koefeler, H.
   Hornemann, T.
   Graier, W. F.
   Malli, R.
   Madeo, F.
   Kratky, D.
TI C16 ceramide is crucial for triacylglycerol-induced apoptosis in
   macrophages
SO CELL DEATH & DISEASE
LA English
DT Article
DE adipose triglyceride lipase deficiency; triacylglycerol; C16 ceramide;
   lipotoxicity; macrophages; apoptosis
ID UNFOLDED PROTEIN RESPONSE; ADIPOSE TRIGLYCERIDE LIPASE;
   ENDOPLASMIC-RETICULUM; MITOCHONDRIAL DYSFUNCTION; CHOLESTEROL;
   ACTIVATION; PATHWAY; METABOLISM; MEMBERS; KINASE
AB Triacylglycerol (TG) accumulation caused by adipose triglyceride lipase (ATGL) deficiency or very low-density lipoprotein (VLDL) loading of wild-type (Wt) macrophages results in mitochondrial-mediated apoptosis. This phenotype is correlated to depletion of Ca2+ from the endoplasmic reticulum (ER), an event known to induce the unfolded protein response (UPR). Here, we show that ER stress in TG-rich macrophages activates the UPR, resulting in increased abundance of the chaperone GRP78/BiP, the induction of pancreatic ER kinase-like ER kinase, phosphorylation and activation of eukaryotic translation initiation factor 2A, the translocation of activating transcription factor (ATF)4 and ATF6 to the nucleus and the induction of the cell death executor CCAAT/enhancer-binding protein homologous protein. C16:0 ceramide concentrations were increased in Atgl-/- and VLDL-loaded Wt macrophages. Overexpression of ceramide synthases was sufficient to induce mitochondrial apoptosis in Wt macrophages. In accordance, inhibition of ceramide synthases in Atgl-/- macrophages by fumonisin B1 (FB1) resulted in specific inhibition of C16: 0 ceramide, whereas intracellular TG concentrations remained high. Although the UPR was still activated in Atgl-/- macrophages, FB1 treatment rescued Atgl-/- macrophages from mitochondrial dysfunction and programmed cell death. We conclude that C16: 0 ceramide elicits apoptosis in Atgl-/- macrophages by activation of the mitochondrial apoptosis pathway. Cell Death and Disease (2012) 3, e280; doi:10.1038/cddis.2012.17; published online 15 March 2012
C1 [Aflaki, E.; Doddapattar, P.; Radovic, B.; Povoden, S.; Vujic, N.; Wegscheider, M.; Graier, W. F.; Malli, R.; Kratky, D.] Med Univ Graz, Ctr Mol Med, Inst Mol Biol & Biochem, A-8010 Graz, Austria.
   [Aflaki, E.] NHGRI, NIH, Mol Neurogenet Sect, Bethesda, MD 20892 USA.
   [Kolb, D.; Koefeler, H.] Med Univ Graz, Inst Cell Biol Histol & Embryol, A-8010 Graz, Austria.
   [Kolb, D.] Med Univ Graz, Med Res Ctr, A-8010 Graz, Austria.
   [Hornemann, T.] Univ Zurich, Inst Clin Chem, CH-8091 Zurich, Switzerland.
   [Madeo, F.] Graz Univ, Inst Mol Biosci, A-8010 Graz, Austria.
RP Kratky, D (reprint author), Med Univ Graz, Ctr Mol Med, Inst Mol Biol & Biochem, Harrachgasse 21, A-8010 Graz, Austria.
EM dagmar.kratky@medunigraz.at
RI Graier, Wolfgang/B-7052-2008; 
OI Graier, Wolfgang/0000-0003-1871-3298; Malli, Roland/0000-0001-6327-8729;
   Kratky, Dagmar/0000-0003-1357-7573
FU Medical University of Graz; Austrian Science Fund FWF [SFB-LIPOTOX F30,
   DK-MCD W1226, P19186, P22832]; Austrian Federal Ministry of Science and
   Research (GEN-AU)
FX This work was supported by the Medical University of Graz (PhD Program
   Molecular Medicine), the Austrian Science Fund FWF (SFB-LIPOTOX F30,
   DK-MCD W1226, P19186, and P22832), and the Austrian Federal Ministry of
   Science and Research (GEN-AU project Genomics of Lipid-associated
   Disorders - GOLD). EA and PD were funded by the PhD Program Molecular
   Medicine of the Medical University of Graz. We thank A Ibovnik for
   excellent technical assistance and I Hindler for mice care.
NR 43
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U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-4889
J9 CELL DEATH DIS
JI Cell Death Dis.
PD MAR
PY 2012
VL 3
AR e280
DI 10.1038/cddis.2012.17
PG 12
WC Cell Biology
SC Cell Biology
GA 917AH
UT WOS:000302143800007
PM 22419109
ER

PT J
AU Gee, M
   Gu, Y
   Fields, JR
   Shiao, YH
AF Gee, M.
   Gu, Y.
   Fields, J. R.
   Shiao, Y-H
TI Stabilization of ribozyme-like cis-noncoding rRNAs induces apoptotic and
   nonapoptotic death in lung cells
SO CELL DEATH & DISEASE
LA English
DT Article
DE rRNA; noncoding RNA; ribozyme; antisense; apoptosis
ID ANTISENSE TRANSCRIPTION; CANCER-CELLS; GENE; INHIBITION; EXPRESSION;
   CLEAVAGE; PROMOTER; CDNAS
AB Bidirectional non-protein-coding RNAs are ubiquitously transcribed from the genome. Convergent sense and antisense transcripts may regulate each other. Here, we examined the convergent cis-noncoding rRNAs (nc-rRNAs) in A5 and E9 lung cancer models. Sense nc-rRNAs extending from rDNA intergenic region to internal transcribed spacer of around 10 kb in length were identified. nc-rRNAs in sense direction exhibited in vitro characteristics of ribozymes, namely, degradation upon incubation with MgCl2 and stabilization by complementary oligonucleotides. Detection of endogenous cleavage-ligation products carrying internal deletion of hundreds to thousands nucleotides by massively parallel sequencing confirmed the catalytic properties. Transfection of oligonucleotides pairing with antisense nc-rRNAs stabilized both target and complementary transcripts, perturbed rRNA biogenesis, and induced massive cell death via apoptotic and/or nonapoptotic mechanisms depending on cell type and treatment. Oligonucleotides targeting cellular sense transcripts are less responsive. Spontaneously detached cells, though rare, also showed accumulation of nc-rRNAs and perturbation of rRNA biogenesis. Direct participation of nc-rRNAs in apoptotic and nonapoptotic death was demonstrated by transfection of synthetic nc-rRNAs encompassing the rDNA promoter. In sum, convergent cis-nc-rRNAs follow a feed-forward mechanism to regulate each other and rRNA biogenesis. This opens an opportunity to disrupt rRNA biogenesis, commonly upregulated in cancers, via inhibition of ribozyme-like activities in nc-rRNAs. Cell Death and Disease (2012) 3, e281; doi:10.1038/cddis.2012.19; published online 15 March 2012
C1 [Shiao, Y-H] NCI Frederick, Comparat Carcinogenesis Lab, NIH, Frederick, MD 21702 USA.
RP Shiao, YH (reprint author), NCI Frederick, Comparat Carcinogenesis Lab, NIH, Bldg 538,Room 205,W 7th St, Frederick, MD 21702 USA.
EM shiaoy@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX We would like to thank Claudia Steward and Robin Steward at the
   Laboratory of Molecular Technology, SAIC-Frederick, for 454 amplicon
   deep sequencing and dideoxy DNA sequencing, Natalia Volfovsky at the
   Advanced Biomedical Computing Center, Information System Program,
   SAIC-Frederick, for bioinformatic analysis of deep-sequencing data, and
   Kathleen Noer and Guity Mohammadi at the Center for Cancer
   Research-Frederick Flow Cytometry Core for the flow analysis. We also
   appreciate colleague Bruce Shapiro for critical reading of the
   manuscript. This research was supported in part by the Intramural
   Research Program of the NIH, National Cancer Institute, Center for
   Cancer Research.
NR 32
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U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-4889
J9 CELL DEATH DIS
JI Cell Death Dis.
PD MAR
PY 2012
VL 3
AR e281
DI 10.1038/cddis.2012.19
PG 11
WC Cell Biology
SC Cell Biology
GA 917AH
UT WOS:000302143800008
PM 22419110
ER

PT J
AU Kosaka, N
   Bernardo, M
   Mitsunaga, M
   Choyke, PL
   Kobayashi, H
AF Kosaka, Nobuyuki
   Bernardo, Marcelino
   Mitsunaga, Makoto
   Choyke, Peter L.
   Kobayashi, Hisataka
TI MR and optical imaging of early micrometastases in lymph nodes: triple
   labeling with nano-sized agents yielding distinct signals
SO CONTRAST MEDIA & MOLECULAR IMAGING
LA English
DT Article
DE iron oxide nanoparticle; quantum dots; lymphatic metastasis; dendrimer;
   MRI
ID MAGNETIC RESONANCE LYMPHANGIOGRAPHY; IN-VIVO TRACKING; QUANTUM-DOT;
   CONTRAST AGENTS; CELLULAR MRI; CANCER-CELLS; STEM-CELLS; BREAST-CANCER;
   REAL-TIME; TUMOR
AB Few imaging methods are available for depicting in vivo cancer cell migration within the lymphatic system. Detection of such early micrometastases requires extremely high target to background. In this study, we dual-labeled human breast cancer cells (MDA-MB468) with a small particle of iron oxide (SPIO) and a quantum dot (QD), and tracked these cells in the lymphatic system in mice using in vivo MRI and optical imaging. A generation-6 gadolinium-dendrimer-based MRI contrast agent (Gd-G6) was employed for visualizing regional lymphatic channels and nodes. Since Gd-G6 shortened T1 leading to high signal, whereas SPIO-labeled cancer cells greatly lowered signal, a small number of cells were simultaneously visualized within the draining lymphatic basins. One million dual-labeled cancer cells were subcutaneously injected into the paws of mice 24?h prior to imaging. Then whole body images were acquired pre- and post-intracutaneous injection of Gd-G6 with 3D-T1w-FFE and balanced-FFE sequences for cancer cell tracking and MR lymphangiography. In vivo MRI clearly visualized labeled cancer cells migrating from the paw to the axillary lymph nodes using draining lymphatics. In vivo optical imaging using a fluorescence surgical microscope demonstrated tiny cancer cell clusters in the axillary lymph node with high spatial resolution. Thus, using a combination of MRI and optical imaging, it is possible to depict macro- and early micrometastases within the lymphatic system. This platform offers a versatile research tool for investigating and treating lymphatic metastases in animal models. Copyright (c) 2011 John Wiley & Sons, Ltd.
C1 [Kosaka, Nobuyuki; Bernardo, Marcelino; Mitsunaga, Makoto; Choyke, Peter L.; Kobayashi, Hisataka] Natl Canc Inst, Mol Imaging Program, NIH, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Bernardo, Marcelino] NCI, SAIC Frederick Inc, NIH, Frederick, MD 21702 USA.
RP Kobayashi, H (reprint author), Natl Canc Inst, Mol Imaging Program, NIH, Ctr Canc Res, Bldg 10,Room B3B69,MSC1088, Bethesda, MD 20892 USA.
EM Kobayash@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
   Cancer Research
FX This research was supported by the Intramural Research Program of the
   National Institutes of Health, National Cancer Institute, Center for
   Cancer Research.
NR 43
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U1 3
U2 41
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1555-4309
J9 CONTRAST MEDIA MOL I
JI Contrast Media Mol. Imaging
PD MAR
PY 2012
VL 7
IS 2
BP 247
EP 253
DI 10.1002/cmmi.489
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 911JU
UT WOS:000301713900017
PM 22434638
ER

PT J
AU Feigenbaum, K
   Brooks, PG
   Chamberlain, CE
   Cochran, E
   Adams-McLean, A
   Malek, R
   Harlan, DM
AF Feigenbaum, Kathryn
   Brooks, Pamela G.
   Chamberlain, Christine E.
   Cochran, Elaine
   Adams-McLean, Allison
   Malek, Rana
   Harlan, David M.
TI The Clinical Center's Blood Glucose Management Service: A Story in
   Quality Integrated Care
SO DIABETES EDUCATOR
LA English
DT Article
ID INTENSIVE INSULIN THERAPY; CRITICALLY-ILL PATIENTS; DIABETIC-PATIENTS;
   GLYCEMIC CONTROL; HYPERGLYCEMIA; IMPACT; TEAM
AB Purpose
   Blood glucose management in the inpatient setting has been shown to be crucial to patient outcomes. As the evidence develops to determine best clinical practices for achieving inpatient glycemic goals, the Clinical Center at the National Institutes of Health has implemented a streamlined multidisciplinary approach to managing blood glucose levels for hospitalized patients. The purpose of this article is to describe the blood glucose management service at the Clinical Center.
   Conclusion
   The blood glucose management service has established a consistent plan of care for diabetes management that has gained acceptance among staff and patients and improved safety and patient outcomes. This plan of care has been applied across various nursing units that serve patient populations on clinical research trials investigating common and rare diseases and treating patients from the United States and around the world.
C1 [Feigenbaum, Kathryn] NIH, Serv Endocrinol, Ctr Clin, Bethesda, MD 20892 USA.
   [Chamberlain, Christine E.] NIH, Clin Res Ctr, Bethesda, MD 20892 USA.
   [Harlan, David M.] Univ Massachusetts, Sch Med, Worcester, MA USA.
   [Malek, Rana] Diabet Branch Staff, Bethesda, MD USA.
RP Feigenbaum, K (reprint author), NIH, Serv Endocrinol, Ctr Clin, 10 Ctr Dr,MSC 1530, Bethesda, MD 20892 USA.
EM kfeigenbaum@nih.gov
NR 21
TC 0
Z9 0
U1 1
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0145-7217
J9 DIABETES EDUCATOR
JI Diabetes Educ.
PD MAR-APR
PY 2012
VL 38
IS 2
BP 194
EP +
DI 10.1177/0145721711430355
PG 8
WC Endocrinology & Metabolism; Public, Environmental & Occupational Health
SC Endocrinology & Metabolism; Public, Environmental & Occupational Health
GA 915ET
UT WOS:000302007500002
PM 22190644
ER

PT J
AU Meunier, S
   Russmann, H
   Shamim, E
   Lamy, JC
   Hallett, M
AF Meunier, Sabine
   Russmann, Heike
   Shamim, Ejaz
   Lamy, Jean-Charles
   Hallett, Mark
TI Plasticity of cortical inhibition in dystonia is impaired after motor
   learning and paired-associative stimulation
SO EUROPEAN JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE dystonia; GABA; human; motor learning; plasticity; transcranial magnetic
   stimulation
ID TRANSCRANIAL MAGNETIC STIMULATION; FOCAL HAND DYSTONIA; LONG-TERM
   POTENTIATION; INTRACORTICAL INHIBITION; WRITERS CRAMP; DIFFERENTIAL
   INDUCTION; SYNAPTIC PLASTICITY; CORTEX EXCITABILITY; PARKINSONS-DISEASE;
   GABA(B) RECEPTOR
AB Artificial induction of plasticity by paired associative stimulation (PAS) in healthy volunteers (HV) demonstrates Hebbian-like plasticity in selected inhibitory networks as well as excitatory networks. In a group of 17 patients with focal hand dystonia and a group of 19 HV, we evaluated how PAS and the learning of a simple motor task influence the circuits supporting long-interval intracortical inhibition (LICI, reflecting activity of GABAB interneurons) and long-latency afferent inhibition (LAI, reflecting activity of somatosensory inputs to the motor cortex). In HV, PAS and motor learning induced long-term potentiation (LTP)-like plasticity of excitatory networks and a lasting decrease of LAI and LICI in the motor representation of the targeted or trained muscle. The better the motor performance, the larger was the decrease of LAI. Although motor performance in the patient group was similar to that of the control group, LAI did not decrease during the motor learning as it did in the control group. In contrast, LICI was normally modulated. In patients the results after PAS did not match those obtained after motor learning: LAI was paradoxically increased and LICI did not exhibit any change. In the normal situation, decreased excitability in inhibitory circuits after induction of LTP-like plasticity may help to shape the cortical maps according to the new sensorimotor task. In patients, the abnormal or absent modulation of afferent and intracortical long-interval inhibition might indicate maladaptive plasticity that possibly contributes to the difficulty that they have to learn a new sensorimotor task.
C1 [Russmann, Heike] NINDS, Dept Psychiat Rehabil, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
   [Meunier, Sabine] GHU Pitie Salpetriere, CNRS UMR 7225, INSERM UMR S975, UPMC,CRICM, Paris, France.
   [Russmann, Heike] Psychiat Univ Clin, Dept Psychiat Rehabil, Zurich, Switzerland.
   [Shamim, Ejaz] Midatlantic Permanente Med Grp, Dept Neurol, Midatlantic Permanente Res Inst, Rockville, MD USA.
   [Lamy, Jean-Charles] Univ Paris 05, CESEM, CNRS UMR 8194, UFR Biomed, Paris, France.
RP Russmann, H (reprint author), NINDS, Dept Psychiat Rehabil, Human Motor Control Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM heike.russmann@chuv.hospvd.ch
RI meunier, sabine/G-7622-2014
OI meunier, sabine/0000-0002-6167-4602
FU National Institutes of Health, National Institute of Neurological
   Disorders and Stroke; Swiss National Funds [PBSKB-104264]; Swiss
   Parkinson Society; Intramural NIH; Fondation pour la Recherche Medicale
   (FRM); NIH; INSERM
FX We thank Devera Schoenberg for editing of the English text. We thank
   Nguyet Dang for technical assistance. This research was funded by the
   Intramural Research Program of the National Institutes of Health,
   National Institute of Neurological Disorders and Stroke. H.R. was funded
   by the Swiss National Funds PBSKB-104264, the Swiss Parkinson Society
   and Intramural NIH. J.-C.L. was funded by the Fondation pour la
   Recherche Medicale (FRM) and Intramural NIH. S.M. was funded by
   Intramural NIH and INSERM.
NR 65
TC 17
Z9 17
U1 0
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0953-816X
J9 EUR J NEUROSCI
JI Eur. J. Neurosci.
PD MAR
PY 2012
VL 35
IS 6
BP 975
EP 986
DI 10.1111/j.1460-9568.2012.08034.x
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 910PR
UT WOS:000301652300015
PM 22429246
ER

PT J
AU Kamda, JD
   Nash, TE
   Singer, SM
AF Kamda, Joel D.
   Nash, Theodore E.
   Singer, Steven M.
TI Giardia duodenalis: Dendritic cell defects in IL-6 deficient mice
   contribute to susceptibility to intestinal infection
SO EXPERIMENTAL PARASITOLOGY
LA English
DT Article
DE Mucosal immunity; Dendritic cells; Interleukin-6; Giardia
ID LAMBLIA INFECTIONS; WATERBORNE GIARDIASIS; ACQUIRED-IMMUNITY; DEPENDENT
   CONTROL; BONE-MARROW; DIFFERENTIATION; VACCINATION; COMMUNITY; PARASITE;
   CULTURE
AB Interleukin (IL)-6 is important in numerous infections. IL-6 can promote T cell survival and differentiation toward Th17 cells, as well as B cell proliferation and differentiation to plasma cells. Giardia duodenalis is a protozoan parasite that replicates in the lumen of the small intestine in humans and many other mammals resulting in diarrhea, cramps and developmental delays in children. IL-6 is required for control of this infection, but it is unclear what its role is or which cells are required to produce this cytokine to generate efficient immunity. We have analyzed infections in a series of chimeric mice in which specific cell types lacked the ability to produce IL-6 in order to determine which sources of IL-6 played an important role in controlling this infection. Analysis of bone marrow chimeras indicate that radiation-sensitive, bone-marrow derived cells must produce IL-6. T cell chimeras show that T cell production of IL-6 is not required. Finally, by transferring dendritic cells from wild-type mice into IL-6 deficient recipients, we show that dendritic cell defects are responsible for the inability of IL-6 deficient mice to respond to Giardia challenge. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Kamda, Joel D.; Singer, Steven M.] Georgetown Univ, Dept Biol, Washington, DC 20057 USA.
   [Nash, Theodore E.] NIAID, Parasit Dis Lab, Bethesda, MD 20896 USA.
RP Singer, SM (reprint author), Georgetown Univ, Dept Biol, 37th & O Sts NW, Washington, DC 20057 USA.
EM sms3@georgetown.edu
OI Singer, Steven/0000-0001-5719-7535
FU NIH [R01AI49565]; NIH, NIAID; Fogarty International Center [5D43
   TW001264]; NIH/NCI [P30-CA051008]; Georgetown University by NIH/NCRR
   [G20-RR025828]
FX The authors would like to thank Sandy Cooper (Animal Care Branch, NIAID,
   NIH) for assistance with bone marrow chimeras and Drs. Brian Kelsall and
   Dragana Jankovic for helpful advice. This work was supported by
   R01AI49565 from NIH. This research was supported in part by the
   Intramural Research Program of the NIH, NIAID. J.D.K. was supported by a
   training grant from the Fogarty International Center (5D43 TW001264).
   The Georgetown Lombardi Shared Resources are partially supported by
   NIH/NCI Grant P30-CA051008 and the Georgetown University Barrier Animal
   Facility by NIH/NCRR Grant G20-RR025828.
NR 26
TC 10
Z9 11
U1 1
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4894
J9 EXP PARASITOL
JI Exp. Parasitol.
PD MAR
PY 2012
VL 130
IS 3
BP 288
EP 291
DI 10.1016/j.exppara.2012.01.003
PG 4
WC Parasitology
SC Parasitology
GA 912SK
UT WOS:000301819900019
PM 22248985
ER

PT J
AU Alter, BP
   Rosenberg, PS
   Giri, N
   Baerlocher, GM
   Lansdorp, PM
   Savage, SA
AF Alter, Blanche P.
   Rosenberg, Philip S.
   Giri, Neelam
   Baerlocher, Gabriela M.
   Lansdorp, Peter M.
   Savage, Sharon A.
TI Telomere length is associated with disease severity and declines with
   age in dyskeratosis congenita
SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
LA English
DT Article
DE bone marrow failure; dyskeratosis congenita; telomeres; longitudinal
   study
ID APLASTIC-ANEMIA; MUTATIONS; TINF2
AB Background
   Dyskeratosis congenita is a cancer-prone bone marrow failure syndrome caused by aberrations in telomere biology.
   Design and Methods
   We studied 65 patients with dyskeratosis congenita and 127 unaffected relatives. Telomere length was measured by automated multicolor flow fluorescence in situ hybridization in peripheral blood leukocyte subsets. We age-adjusted telomere length using Z-scores (standard deviations from the mean for age).
   Results
   We confirmed that telomere lengths below the first percentile for age are very sensitive and specific for the diagnosis of dyskeratosis congenita. We provide evidence that lymphocytes alone and not granulocytes may suffice for clinical screening, while lymphocyte subsets may be required for challenging cases, including identification of silent carriers. We show for the first time using flow fluorescence in situ hybridization that the shortest telomeres are associated with severe variants (Hoyeraal-Hreidarsson and Revesz syndromes), mutations in DKC1, TINF2, or unknown genes, and moderate or severe aplastic anemia. In the first longitudinal follow up of dyskeratosis congenita patients, we demonstrate that telomere lengths decline with age, in contrast to the apparent stable telomere length observed in cross-sectional data.
   Conclusions
   Telomere length by flow fluorescence in situ hybridization is an important diagnostic test for dyskeratosis congenita; age-adjusted values provide a quantitative measure of disease severity (clinical subset, mutated gene, and degree of bone marrow failure). Patients with dyskeratosis congenita have accelerated telomere shortening. This study is registered at www.clinicaltrials.gov (identifier: NCT00027274).
C1 [Alter, Blanche P.; Giri, Neelam; Savage, Sharon A.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA.
   [Rosenberg, Philip S.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA.
   [Baerlocher, Gabriela M.] Univ Hosp Bern, CH-3010 Bern, Switzerland.
   [Lansdorp, Peter M.] British Columbia Canc Res Ctr, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada.
RP Alter, BP (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,Execut Plaza,S Room 7020, Rockville, MD 20852 USA.
EM alterb@mail.nih.gov
RI Savage, Sharon/B-9747-2015
OI Savage, Sharon/0000-0001-6006-0740
FU National Institutes of Health; National Cancer Institute; Westat,
   Incorporated [N02-CP-91026, N02-CP-11019, HHSN261200655001C]; Swiss
   National Foundation; Bernese Cancer League; Canadian Institutes of
   Health Research [RMF-92093]; NIH [R01GM094146]; Canadian Cancer Society;
   Terry Fox Foundation [018006, 105265]
FX Funding: this research was supported in part by the Intramural Research
   Program of the National Institutes of Health and the National Cancer
   Institute (BPA, NG, SAS, PSR), and by contracts N02-CP-91026,
   N02-CP-11019 and HHSN261200655001C with Westat, Incorporated. GMB was
   supported by the Swiss National Foundation and the Bernese Cancer
   League. Work in the Lansdorp laboratory was supported by grants from the
   Canadian Institutes of Health Research (RMF-92093), the NIH
   (R01GM094146), the Canadian Cancer Society and the Terry Fox Foundation
   (018006 and 105265).
NR 18
TC 48
Z9 51
U1 2
U2 14
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 MAR
PY 2012
VL 97
IS 3
BP 353
EP 359
DI 10.3324/haematol.2011.055269
PG 7
WC Hematology
SC Hematology
GA 914TP
UT WOS:000301975700010
PM 22058220
ER

PT J
AU Pidala, J
   Vogelsang, G
   Martin, P
   Chai, XY
   Storer, B
   Pavletic, S
   Weisdorf, DJ
   Jagasia, M
   Cutler, C
   Palmer, J
   Jacobsohn, D
   Arai, S
   Lee, SJ
AF Pidala, Joseph
   Vogelsang, Georgia
   Martin, Paul
   Chai, Xiaoyu
   Storer, Barry
   Pavletic, Steven
   Weisdorf, Daniel J.
   Jagasia, Madan
   Cutler, Corey
   Palmer, Jeanne
   Jacobsohn, David
   Arai, Sally
   Lee, Stephanie J.
TI Overlap subtype of chronic graft-versus-host disease is associated with
   an adverse prognosis, functional impairment, and inferior
   patient-reported outcomes: a Chronic Graft-versus-Host Disease
   Consortium study
SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
LA English
DT Article
DE overlap subtype; graft-versus-host disease; GVHD; prognosis
ID QUALITY-OF-LIFE; HEMATOPOIETIC-CELL TRANSPLANTATION; CONSENSUS
   DEVELOPMENT PROJECT; BONE-MARROW-TRANSPLANTATION; WORKING GROUP-REPORT;
   CLINICAL-TRIALS; CRITERIA; SEVERITY; SCALE; VALIDATION
AB Background
   The National Institutes of Health Consensus Conference proposed the term "overlap" graft-versus-host disease to describe the situation when both acute and chronic graft-versus-host disease are present.
   Design and Methods
   We examined whether the overlap subtype of graft-versus-host disease was associated with a different prognosis, functional limitations, or patient-reported outcomes compared to "classic" chronic graft-versus-host disease without any acute features.
   Results
   Prospective data were collected from 427 patients from nine centers. Patients were classified as having overlap (n=352) or classic chronic (n=75) graft-versus-host disease based on reported organ involvement. Overlap cases had a significantly shorter median time from transplantation to cohort enrollment (P=0.01), were more likely to be incident cases (P < 0.001), and had a lower platelet count at onset of the graft-versus-host disease (P < 0.001). Patients with overlap graft-versus-host disease had significantly greater functional impairment measured by a 2-minute walk test, higher symptom burden and lower Human Activity Profile scores. Quality of life was similar, except patients with overlap graft-versus-host disease had worse social functioning, assessed by the Short Form-36. Multivariable analysis utilizing time-varying covariates demonstrated that the overlap subtype of graft-versus-host disease was associated with worse overall survival (HR 2.1, 95% CI 1.1-4.7; P=0.03) and higher non-relapse mortality (HR 2.8, 95% CI 1.2-8.3; P=0.02) than classic chronic graft-versus-host disease.
   Conclusions
   These findings suggest that the presence of acute features in patients with chronic graft-versus-host disease is a marker of adverse prognosis, greater functional impairment, and higher symptom burden.
C1 [Pidala, Joseph] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
   [Vogelsang, Georgia] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA.
   [Martin, Paul; Chai, Xiaoyu; Storer, Barry; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
   [Pavletic, Steven] NCI, Bethesda, MD 20892 USA.
   [Weisdorf, Daniel J.] Univ Minnesota, Minneapolis, MN USA.
   [Jagasia, Madan] Vanderbilt Univ, Nashville, TN USA.
   [Cutler, Corey] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Palmer, Jeanne] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
   [Jacobsohn, David] Childrens Mem Hosp, Chicago, IL 60614 USA.
   [Arai, Sally] Stanford Univ, Stanford, CA 94305 USA.
RP Pidala, J (reprint author), Blood & Marrow Transplantat Moffitt Canc Ctr, 12902 Magnolia Dr,FOB 3308, Tampa, FL 33612 USA.
EM joseph.pidala@moffitt.org
FU NCI NIH HHS [P30 CA015704, P30 CA076292, U54 CA163438]
NR 33
TC 24
Z9 24
U1 0
U2 0
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 MAR
PY 2012
VL 97
IS 3
BP 451
EP 458
DI 10.3324/haematol.2011.055186
PG 8
WC Hematology
SC Hematology
GA 914TP
UT WOS:000301975700024
PM 22058206
ER

PT J
AU Merikangas, KR
AF Merikangas, Kathleen Ries
TI Update on the Genetics of Migraine
SO HEADACHE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY; METAANALYSIS; POPULATION;
   DISORDER; DISEASES
AB Migraine is a common neurological disorder and is characterized by debilitating head pain and an assortment of additional symptoms which can include nausea, emesis, photophobia, phonophobia, and occasionally, visual sensory disturbances. A number of genes have been implicated in the pathogenesis of this disease, including genes involved in regulating the vascular system. Of particular importance are the methylenetetrahydrofolate reductase gene ( MTHFR) and the role it plays in migraine with aura. Migraine with aura has previously been shown to have a significant comorbidity with stroke, making the vascular class of genes a priority for migraine studies. In this report, we outline the importance of the MTHFR gene in migraine and also discuss the use of a genetic isolate to investigate MTHFR genetic variants. From this study, 3 MTHFR single nucleotide polymorphisms showing association with migraine in the Norfolk Island population have been identified, thus reinforcing the potential role of MTHFR in migraine susceptibility. Further studies will continue to build a gene profile of variants involved in the complex disease migraine and improve understanding of the underlying genetic causes of this disorder.
C1 NIMH, Genet Epidemiol Res Branch, Bethesda, MD 20892 USA.
RP Merikangas, KR (reprint author), NIMH, Genet Epidemiol Res Branch, 35 Convent Dr,MSC3720, Bethesda, MD 20892 USA.
NR 19
TC 1
Z9 2
U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0017-8748
J9 HEADACHE
JI Headache
PD MAR
PY 2012
VL 52
IS 3
BP 521
EP 522
DI 10.1111/j.1526-4610.2012.02107.x
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA 904WE
UT WOS:000301228800019
PM 22375730
ER

PT J
AU Ampofo, WK
   Baylor, N
   Cobey, S
   Cox, NJ
   Daves, S
   Edwards, S
   Ferguson, N
   Grohmann, G
   Hay, A
   Katz, J
   Kullabutr, K
   Lambert, L
   Levandowski, R
   Mishra, AC
   Monto, A
   Siqueira, M
   Tashiro, M
   Waddell, AL
   Wairagkar, N
   Wood, J
   Zambon, M
   Zhang, WQ
AF Ampofo, William K.
   Baylor, Norman
   Cobey, Sarah
   Cox, Nancy J.
   Daves, Sharon
   Edwards, Steven
   Ferguson, Neil
   Grohmann, Gary
   Hay, Alan
   Katz, Jacqueline
   Kullabutr, Kornnika
   Lambert, Linda
   Levandowski, Roland
   Mishra, A. C.
   Monto, Arnold
   Siqueira, Marilda
   Tashiro, Masato
   Waddell, Anthony L.
   Wairagkar, Niteen
   Wood, John
   Zambon, Maria
   Zhang, Wenqing
CA WHO Writing Grp
TI Improving influenza vaccine virus selectionReport of a WHO informal
   consultation held at WHO headquarters, Geneva, Switzerland, 14-16 June
   2010
SO INFLUENZA AND OTHER RESPIRATORY VIRUSES
LA English
DT Article
DE influenza vaccine viruses; vaccine virus selection; WHO recommendations
AB For almost 60 years, the WHO Global Influenza Surveillance and Response System (GISRS) has been the key player in monitoring the evolution and spread of influenza viruses and recommending the strains to be used in human influenza vaccines. The GISRS has also worked to continually monitor and assess the risk posed by potential pandemic viruses and to guide appropriate public health responses. The expanded and enhanced role of the GISRS following the adoption of the International Health Regulations (2005), recognition of the continuing threat posed by avian H5N1 and the aftermath of the 2009 H1N1 pandemic provide an opportune time to critically review the process by which influenza vaccine viruses are selected. In addition to identifying potential areas for improvement, such a review will also help to promote greater appreciation by the wider influenza and policy-making community of the complexity of influenza vaccine virus selection. The selection process is highly coordinated and involves continual year-round integration of virological data and epidemiological information by National Influenza Centres (NICs), thorough antigenic and genetic characterization of viruses by WHO Collaborating Centres (WHOCCs) as part of selecting suitable candidate vaccine viruses, and the preparation of suitable reassortants and corresponding reagents for vaccine standardization by WHO Essential Regulatory Laboratories (ERLs). Ensuring the optimal effectiveness of vaccines has been assisted in recent years by advances in molecular diagnosis and the availability of more extensive genetic sequence data. However, there remain a number of challenging constraints including variations in the assays used, the possibility of complications resulting from non-antigenic changes, the limited availability of suitable vaccine viruses and the requirement for recommendations to be made up to a year in advance of the peak of influenza season because of production constraints. Effective collaboration and coordination between human and animal influenza networks is increasingly recognized as an essential requirement for the improved integration of data on animal and human viruses, the identification of unusual influenza A viruses infecting human, the evaluation of pandemic risk and the selection of candidate viruses for pandemic vaccines. Training workshops, assessments and donations have led to significant increases in trained laboratory personnel and equipment with resulting expansion in both geographical surveillance coverage and in the capacities of NICs and other laboratories. This has resulted in a significant increase in the volume of information reported to WHO on the spread, intensity and impact of influenza. In addition, initiatives such as the WHO Shipment Fund Project have facilitated the timely sharing of clinical specimens and virus isolates and contributed to a more comprehensive understanding of the global distribution and temporal circulation of different viruses. It will be important to sustain and build upon the gains made in these and other areas. Although the haemagglutination inhibition (HAI) assay is likely to remain the assay of choice for the antigenic characterization of viruses in the foreseeable future, alternative assays for example based upon advanced recombinant DNA and protein technologies may be more adaptable to automation. Other technologies such as microtitre neuraminidase inhibition assays may also have significant implications for both vaccine virus selection and vaccine development.
   Microneutralization assays provide an important adjunct to the HAI assay in virus antigenic characterization. Improvements in the use and potential automation of such assays should facilitate large-scale serological studies, while other advanced techniques such as epitope mapping should allow for a more accurate assessment of the quality of a protective immune response and aid the development of additional criteria for measuring immunity. Standardized seroepidemiological surveys to assess the impact of influenza in a population could help to establish well-characterized banks of age-stratified representative sera as a national, regional and global resource, while providing direct evidence of the specific benefits of vaccination. Advances in high-throughput genetic sequencing coupled with advanced bioinformatics tools, together with more X-ray crystallographic data, should accelerate understanding of the genetic and phenotypic changes that underlie virus evolution and more specifically help to predict the influence of amino acid changes on virus antigenicity. Complex mathematical modelling techniques are increasingly being used to gain insights into the evolution and epidemiology of influenza viruses. However, their value in predicting the timing and nature of future antigenic and genetic changes is likely to be limited at present. The application of simpler non-mechanistic statistical algorithms, such as those already used as the basis of antigenic cartography, and phylogenetic modelling are more likely to be useful in facilitating vaccine virus selection and in aiding assessment of the pandemic potential of avian and other animal influenza viruses. The adoption of alternative vaccine technologies such as live-attenuated, quadrivalent or non-HA-based vaccines has significant implications for vaccine virus selection, as well as for vaccine regulatory and manufacturing processes. Recent collaboration between the GISRS and vaccine manufacturers has resulted in the increased availability of egg isolates and high-growth reassortants for vaccine production, the development of qualified cell cultures and the investigation of alternative methods of vaccine potency testing. WHO will continue to support these and other efforts to increase the reliability and timeliness of the global influenza vaccine supply. The WHO GISRS and its partners are continually working to identify improvements, harness new technologies and strengthen and sustain collaboration. WHO will continue in its central role of coordinating worldwide expertise to meet the increasing public health need for influenza vaccines and will support efforts to improve the vaccine virus selection process, including through the convening of periodic international consultations.
C1 [Baylor, Norman] US FDA, Rockville, MD 20857 USA.
   [Ampofo, William K.] Natl Influenza Ctr, Accra, Ghana.
   [Cobey, Sarah] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
   [Cox, Nancy J.; Katz, Jacqueline] Ctr Dis Control & Prevent CDC, Atlanta, GA USA.
   [Daves, Sharon] NAMRU 3, Cairo, Egypt.
   [Edwards, Steven] Network Expertise Anim Influenzas OFFLU Steering, Hereford, England.
   [Ferguson, Neil] Univ London Imperial Coll Sci Technol & Med, Sch Med St Marys, London, England.
   [Grohmann, Gary] Therapeut Goods Adm Labs, Symonston, Australia.
   [Hay, Alan] Natl Inst Med Res, London NW7 1AA, England.
   [Kullabutr, Kornnika] Minist Publ Hlth, Nonthaburi, Thailand.
   [Lambert, Linda] NIH, Bethesda, MD 20892 USA.
   [Levandowski, Roland] Freelancer, Bethesda, MD USA.
   [Mishra, A. C.] Natl Influenza Ctr, Pune, Maharashtra, India.
   [Monto, Arnold] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA.
   [Siqueira, Marilda] Inst Oswaldo Cruz, BR-20001 Rio De Janeiro, Brazil.
   [Tashiro, Masato] WHO Collaborating Ctr Reference & Res Influenza, Tokyo, Japan.
   [Waddell, Anthony L.] Freelancer, Stanley, Hong Kong, Peoples R China.
   [Wairagkar, Niteen; Zhang, Wenqing] WHO, Zurich, Switzerland.
   [Wood, John] NIBSC, Potters Bar, Herts, England.
   [Zambon, Maria] Hlth Protect Agcy, London, England.
RP Zhang, WQ (reprint author), WHO HQ Geneva, Geneva, Switzerland.
EM zhangw@who.int
RI Ferguson, Neil/B-8578-2008; HERAUD, Jean-Michel/O-1464-2013; perumal,
   murugiah/D-1565-2012
OI Ferguson, Neil/0000-0002-1154-8093; HERAUD,
   Jean-Michel/0000-0003-1107-0859; Russell, Colin/0000-0002-2113-162X; 
NR 0
TC 28
Z9 28
U1 0
U2 23
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1750-2640
J9 INFLUENZA OTHER RESP
JI Influenza Other Respir. Viruses
PD MAR
PY 2012
VL 6
IS 2
BP 142
EP +
DI 10.1111/j.1750-2659.2011.00277.x
PG 16
WC Infectious Diseases; Virology
SC Infectious Diseases; Virology
GA 897VZ
UT WOS:000300689300010
ER

PT J
AU Kim, JS
   Chung, CK
   Jo, HJ
   Lee, JM
   Kown, JS
AF Kim, June Sic
   Chung, Chun Kee
   Jo, Hang Joon
   Lee, Jong Min
   Kown, Jun Soo
TI Regional thinning of cerebral cortical thickness in first-episode and
   chronic schizophrenia
SO INTERNATIONAL JOURNAL OF IMAGING SYSTEMS AND TECHNOLOGY
LA English
DT Article
DE schizophrenia; cortical thickness; first-episode; chronic
ID GRAY-MATTER VOLUME; FIRST-EPISODE SCHIZOPHRENIA; CHILDHOOD-ONSET
   SCHIZOPHRENIA; AUTOMATED 3-D EXTRACTION; LEFT TEMPORAL-LOBE;
   PARCELLATION METHOD; HIPPOCAMPAL VOLUME; PSYCHOTIC-PATIENTS; PLANUM
   TEMPORALE; BRAIN MORPHOLOGY
AB First-episode schizophrenia and chronic schizophrenia have different patterns of cortical gray matter loss, due to differences in the period of illness. Differences in the reduction of cortical thickness between first-episode and chronic schizophrenia has not yet been addressed using a technique of measuring cortical thickness. The goal of this study is to identify differences in cerebral cortical thickness between first-episode schizophrenic patients and matched normal controls as well as between chronic schizophrenic patients and matched normal controls. Thirty-five chronic and 24 first-episode schizophrenic patients were compared with each age- and sex-matched control group, respectively. To measure cortical thickness, we utilized an inner and outer cortical surface reconstruction algorithm. Cortical thickness was directly measured as the distance between the two surfaces. Statistical analysis was performed with diffusion smoothing along cortical manifolds, and surface normalization on a sphere model. There were no significant changes in global mean thickness and cerebral gray matter volume in both first-episode and chronic schizophrenia patients. However, we observed regional thinning of cortical thickness, most significantly in the superior temporal gyrus of first-episode schizophrenic patients. In chronic schizophrenia, larger regions including the prefrontal cortex (PF) were significantly thinned compared to the first-episode group. This suggests that the duration of illness affects cortical thinning in the PF, as well as the extent of cortical thinning. (c) 2012 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 22, 7380, 2012
C1 [Kim, June Sic; Chung, Chun Kee] Seoul Natl Univ Hosp, MEG Ctr, Dept Neurosurg, Seoul 110744, South Korea.
   [Jo, Hang Joon] NIMH, NIH, Bethesda, MD 20892 USA.
   [Lee, Jong Min] Hanyang Univ, Dept Biomed Engn, Seoul 133791, South Korea.
   [Kown, Jun Soo] Seoul Natl Univ Hosp, Dept Psychiat, Seoul 110744, South Korea.
RP Chung, CK (reprint author), Seoul Natl Univ Hosp, MEG Ctr, Dept Neurosurg, Seoul 110744, South Korea.
EM chungc@snu.ac.kr
RI Chung, Chun Kee/J-5650-2012; JO, HANG JOON/D-1775-2011
OI Chung, Chun Kee/0000-0003-3485-2327; JO, HANG JOON/0000-0002-9180-3831
FU Ministry of Education, Science and Technology [2011-0030103]; National
   Research Foundation of Korea (NRF)
FX Grant sponsor: The Ministry of Education, Science and Technology; Grant
   number: (No. 2011-0030103); This research was supported by the Original
   Technology Research Program for Brain Science through the National
   Research Foundation of Korea (NRF).
NR 86
TC 0
Z9 0
U1 3
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0899-9457
J9 INT J IMAG SYST TECH
JI Int. J. Imaging Syst. Technol.
PD MAR
PY 2012
VL 22
IS 1
SI SI
BP 73
EP 80
DI 10.1002/ima.22002
PG 8
WC Engineering, Electrical & Electronic; Optics; Imaging Science &
   Photographic Technology
SC Engineering; Optics; Imaging Science & Photographic Technology
GA 895OH
UT WOS:000300505200010
ER

PT J
AU Morocz, IA
   Janoos, F
   van Gelderen, P
   Manor, D
   Karni, A
   Breznitz, Z
   von Aster, M
   Kushnir, T
   Shalev, R
AF Morocz, Istvana Akos
   Janoos, Firdaus
   van Gelderen, Peter
   Manor, David
   Karni, Avi
   Breznitz, Zvia
   von Aster, Michael
   Kushnir, Tammar
   Shalev, Ruth
TI Time-resolved and spatio-temporal analysis of complex cognitive
   processes and their role in disorders like developmental dyscalculia
SO INTERNATIONAL JOURNAL OF IMAGING SYSTEMS AND TECHNOLOGY
LA English
DT Article
DE mental arithmetic; developmental dyscalculia; fMRI; spatio-temporal
   analysis; functional brain mapping
ID ANTERIOR CINGULATE CORTEX; VERBAL WORKING-MEMORY; HUMAN PARIETAL LOBE;
   PREFRONTAL CORTEX; HUMAN BRAIN; VELOCARDIOFACIAL SYNDROME; APPROXIMATE
   CALCULATION; ATTENTIONAL MODULATION; ATYPICAL TRAJECTORIES; NUMBER
   DEVELOPMENT
AB The aim of this article is to report on the importance and challenges of a time-resolved and spatio-temporal analysis of fMRI data from complex cognitive processes and associated disorders using a study on developmental dyscalculia (DD). Participants underwent fMRI while judging the incorrectness of multiplication results, and the data were analyzed using a sequence of methods, each of which progressively provided more a detailed picture of the spatio-temporal aspect of this disease. Healthy subjects and subjects with DD performed alike behaviorally, though they exhibited parietal disparities using traditional voxel-based group analyses. Further and more detailed differences, however, surfaced with a time-resolved examination of the neural responses during the experiment. While performing intergroup comparisons, a third group of subjects with dyslexia but with no arithmetic difficulties was included to test the specificity of the analysis and strengthen the statistical base with overall 58 subjects. Surprisingly, the analysis showed a functional dissimilarity during an initial reading phase for the group of dyslexic but otherwise normal subjects, with respect to controls, though only numerical digits and no alphabetic characters were presented. Thus, our results suggest that time-resolved multivariate analysis of complex experimental paradigms has the ability to yield powerful new clinical insights about abnormal brain function. Similarly, a detailed compilation of aberrations in the functional cascade may have much greater potential to delineate the core processing problems in mental disorders. (c) 2012 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 22, 8196, 2012
C1 [Morocz, Istvana Akos; Janoos, Firdaus] Harvard Univ, Dept Radiol, Sch Med, Brigham & Womens Hosp, Boston, MA 02445 USA.
   [Morocz, Istvana Akos] Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel.
   [Morocz, Istvana Akos; Karni, Avi; Breznitz, Zvia] Univ Haifa, Edmond J Safra Brain Res Ctr, Study Learning Disabil, IL-31999 Haifa, Israel.
   [van Gelderen, Peter] Natl Inst Neurol Disorders & Stroke, Adv MRI, NIH, Bethesda, MD USA.
   [Manor, David; Karni, Avi; Kushnir, Tammar] Sheba Med Ctr, Dept Diagnost Imaging, Tel Hashomer, Israel.
   [von Aster, Michael] German Red Cross Hosp, Dept Child & Adolescent Psychiat, Berlin, Germany.
   [Shalev, Ruth] Shaare Zedek Med Ctr, Dept Pediat Neurol, Jerusalem, Israel.
RP Morocz, IA (reprint author), Harvard Univ, Dept Radiol, Sch Med, Brigham & Womens Hosp, Boston, MA 02445 USA.
EM pisti@bwh.harvard.edu
FU Ministry of Absorption of Israel; Feinberg Graduate School at Weizmann
   Institute of Science in Rehovot, Israel; Bar Training Fellowship Award
   in Translational Neuroscience at Brigham; Women's Hospital in Boston, MA
FX Grant sponsors: Ministry of Absorption of Israel (IAM), Feinberg
   Graduate School at Weizmann Institute of Science in Rehovot, Israel, and
   Bar Training Fellowship Award in Translational Neuroscience at Brigham
   and Women's Hospital in Boston, MA. PvG is staff scientist at the
   National Institute of Neurological Disorders and Stroke (NINDS at NIH)
   and at the Advanced MRI Laboratory (AMRI at NIH) where the PRESTO pulse
   sequence used in this study was developed.
NR 98
TC 0
Z9 0
U1 5
U2 16
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0899-9457
J9 INT J IMAG SYST TECH
JI Int. J. Imaging Syst. Technol.
PD MAR
PY 2012
VL 22
IS 1
SI SI
BP 81
EP 96
DI 10.1002/ima.22009
PG 16
WC Engineering, Electrical & Electronic; Optics; Imaging Science &
   Photographic Technology
SC Engineering; Optics; Imaging Science & Photographic Technology
GA 895OH
UT WOS:000300505200011
PM 22368322
ER

PT J
AU Capone, R
   Jang, H
   Kotler, SA
   Connelly, L
   Arce, FT
   Ramachandran, S
   Kagan, BL
   Nussinov, R
   Lal, R
AF Capone, Ricardo
   Jang, Hyunbum
   Kotler, Samuel A.
   Connelly, Laura
   Arce, Fernando Teran
   Ramachandran, Srinivasan
   Kagan, Bruce L.
   Nussinov, Ruth
   Lal, Ratnesh
TI All-D-Enantiomer of beta-Amyloid Peptide Forms Ion Channels in Lipid
   Bilayers
SO JOURNAL OF CHEMICAL THEORY AND COMPUTATION
LA English
DT Article
ID ATOMIC-FORCE MICROSCOPY; ALZHEIMERS-DISEASE; MOLECULAR-DYNAMICS;
   ANTIMICROBIAL PEPTIDE; ELECTRICAL-PROPERTIES; PHOSPHOLIPID-BILAYER;
   GRAMICIDIN CHANNEL; ESCHERICHIA-COLI; CALCIUM-CHANNELS; PIG INTESTINE
AB Alzheimer's disease (AD) is the most common type of senile dementia in aging populations. Amyloid beta (A beta)-mediated dysregulation of ionic homeostasis is the prevailing underlying mechanism leading to synaptic degeneration and neuronal death. A beta-dependent ionic dysregulation most likely occurs either directly via unregulated ionic transport through the membrane or indirectly via A beta binding to cell membrane receptors and subsequent opening of existing ion channels or transporters. Receptor binding is expected to involve a high degree of stereospecificity. Here, we investigated whether an A beta peptide enantiomer, whose entire sequence consists of D-amino acids, can form ion-conducting channels; these channels can directly mediate A beta effects even in the absence of receptor peptide interactions. Using complementary approaches of planar lipid bilayer (PLB) electrophysiological recordings and molecular dynamics (MD) simulations, we.;how that the (L)-A beta isomer exhibits ion conductance behavior in the bilayer indistinguishable from that described earlier for the (L)-A beta isomer. The D isomer forms channel-like pores with heterogeneous ionic conductance similar to the (L)-A beta isomer channels, and the D-isomer channel conductance is blocked by Zn2+, a known blocker of L-A beta isomer channels. MD simulations further verify formation of beta-barrel. like A beta channels with D- and L-isomers, illustrating that both D- and L-A beta barrels can conduct cations. The calculated values of the single-channel conductance are approximately in the range of the experimental values. These findings are in agreement with amyloids forming Ca2+ leaking, unregulated channels in AD, and suggest that A beta toxicity is mediated through a receptor-independent, nonstereoselective mechanism.
C1 [Jang, Hyunbum; Nussinov, Ruth] NCI Frederick, SAIC Frederick, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA.
   [Capone, Ricardo; Kotler, Samuel A.; Connelly, Laura; Arce, Fernando Teran; Ramachandran, Srinivasan; Lal, Ratnesh] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.
   [Capone, Ricardo; Kotler, Samuel A.; Connelly, Laura; Arce, Fernando Teran; Ramachandran, Srinivasan; Lal, Ratnesh] Univ Calif San Diego, Dept Mech & Aerosp Engn, La Jolla, CA 92093 USA.
   [Capone, Ricardo; Kotler, Samuel A.; Connelly, Laura; Arce, Fernando Teran; Ramachandran, Srinivasan; Lal, Ratnesh] Univ Calif San Diego, Mat Sci Program, La Jolla, CA 92093 USA.
   [Kagan, Bruce L.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Dept Psychiat, Los Angeles, CA 90024 USA.
   [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel.
RP Nussinov, R (reprint author), NCI Frederick, SAIC Frederick, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA.
EM ruthnu@helix.nih.gov; rlal@ucsd.edu
RI Capone, Ricardo/D-1943-2010; Ramachandran, Srinivasan/G-5300-2010
OI Capone, Ricardo/0000-0002-7327-9837; Ramachandran,
   Srinivasan/0000-0002-4912-0279
FU National Institutes of Health (National Institute on Aging) [AG028709];
   National Cancer Institute, National Institutes of Health
   [HHSN261200800001E]; NIH; National Cancer Institute; Center for Cancer
   Research
FX This research was supported by the National Institutes of Health
   (National Institute on Aging AG028709 to RL.). This project has been
   funded in whole or in part with Federal funds from the National Cancer
   Institute, National Institutes of Health, under contract no.
   HHSN261200800001E. This research was supported (in part) by the
   Intramural Research Program of the NIH, National Cancer Institute,
   Center for Cancer Research. All simulations were performed using the
   high-performance computational facilities of the Biowulf PC/Linux
   cluster at the National Institutes of Health, Bethesda, MD
   (http://biowulf.nih.gov).
NR 78
TC 26
Z9 26
U1 1
U2 22
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1549-9618
J9 J CHEM THEORY COMPUT
JI J. Chem. Theory Comput.
PD MAR
PY 2012
VL 8
IS 3
BP 1143
EP 1152
DI 10.1021/ct200885r
PG 10
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 907CV
UT WOS:000301396300037
PM 22423218
ER

PT J
AU Wang, CH
   Dowling, JJ
   North, K
   Schroth, MK
   Sejersen, T
   Shapiro, F
   Bellini, J
   Weiss, H
   Guillet, M
   Amburgey, K
   Apkon, S
   Bertini, E
   Bonnemann, C
   Clarke, N
   Connolly, AM
   Estournet-Mathiaud, B
   Fitzgerald, D
   Florence, JM
   Gee, R
   Gurgel-Giannetti, J
   Glanzman, AM
   Hofmeister, B
   Jungbluth, H
   Koumbourlis, AC
   Laing, NG
   Main, M
   Morrison, LA
   Munns, C
   Rose, K
   Schuler, PM
   Sewry, C
   Storhaug, K
   Vainzof, M
   Yuan, N
AF Wang, Ching H.
   Dowling, James J.
   North, Kathryn
   Schroth, Mary K.
   Sejersen, Thomas
   Shapiro, Frederic
   Bellini, Jonathan
   Weiss, Hali
   Guillet, Marc
   Amburgey, Kimberly
   Apkon, Susan
   Bertini, Enrico
   Bonnemann, Carsten
   Clarke, Nigel
   Connolly, Anne M.
   Estournet-Mathiaud, Brigitte
   Fitzgerald, Dominic
   Florence, Julaine M.
   Gee, Richard
   Gurgel-Giannetti, Juliana
   Glanzman, Allan M.
   Hofmeister, Brittany
   Jungbluth, Heinz
   Koumbourlis, Anastassios C.
   Laing, Nigel G.
   Main, Marion
   Morrison, Leslie A.
   Munns, Craig
   Rose, Kristy
   Schuler, Pamela M.
   Sewry, Caroline
   Storhaug, Kari
   Vainzof, Mariz
   Yuan, Nanci
TI Consensus Statement on Standard of Care for Congenital Myopathies
SO JOURNAL OF CHILD NEUROLOGY
LA English
DT Article
DE standard of care; congenital myopathy; rod; myotubular; centronuclear;
   central core; cap; nemaline; zebra body; myosin storage
ID CENTRAL CORE DISEASE; ONSET NEMALINE MYOPATHY; LINKED MYOTUBULAR
   MYOPATHY; DUCHENNE MUSCULAR-DYSTROPHY; FIBER-TYPE DISPROPORTION;
   MULTI-MINICORE DISEASE; MALIGNANT HYPERTHERMIA; NEUROMUSCULAR DISEASE;
   NONINVASIVE VENTILATION; CENTRONUCLEAR MYOPATHY
AB Recent progress in scientific research has facilitated accurate genetic and neuropathological diagnosis of congenital myopathies. However, given their relatively low incidence, congenital myopathies remain unfamiliar to the majority of care providers, and the levels of patient care are extremely variable. This consensus statement aims to provide care guidelines for congenital myopathies. The International Standard of Care Committee for Congenital Myopathies worked through frequent e-mail correspondences, periodic conference calls, 2 rounds of online surveys, and a 3-day workshop to achieve a consensus for diagnostic and clinical care recommendations. The committee includes 59 members from 10 medical disciplines. They are organized into 5 working groups: genetics/diagnosis, neurology, pulmonology, gastroenterology/nutrition/speech/oral care, and orthopedics/rehabilitation. In each care area the authors summarize the committee's recommendations for symptom assessments and therapeutic interventions. It is the committee's goal that through these recommendations, patients with congenital myopathies will receive optimal care and improve their disease outcome.
C1 [Wang, Ching H.; Bellini, Jonathan; Weiss, Hali; Gee, Richard; Hofmeister, Brittany; Yuan, Nanci] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
   [Dowling, James J.; Amburgey, Kimberly] Univ Michigan, Ann Arbor, MI 48109 USA.
   [North, Kathryn; Clarke, Nigel; Fitzgerald, Dominic; Munns, Craig; Rose, Kristy] Univ Sydney, Westmead, NSW 2145, Australia.
   [Schroth, Mary K.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA.
   [Sejersen, Thomas] Karolinska Inst, Stockholm, Sweden.
   [Shapiro, Frederic] Harvard Univ, Sch Med, Boston, MA USA.
   [Guillet, Marc] Fdn Bldg Strength, Palo Alto, CA USA.
   [Apkon, Susan] Seattle Childrens Hosp, Seattle, WA USA.
   [Bertini, Enrico] Bambino Gesu Childrens Res Hosp, Rome, Italy.
   [Bonnemann, Carsten] NIH, Bethesda, MD 20892 USA.
   [Connolly, Anne M.; Florence, Julaine M.] Washington Univ, Sch Med, St Louis, MO USA.
   [Estournet-Mathiaud, Brigitte] Hop Raymond Poincare, Garches, France.
   [Gurgel-Giannetti, Juliana] Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil.
   [Glanzman, Allan M.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
   [Jungbluth, Heinz] Evelina Childrens Hosp, London, England.
   [Koumbourlis, Anastassios C.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
   [Laing, Nigel G.] Univ Western Australia, Nedlands, WA 6009, Australia.
   [Main, Marion; Sewry, Caroline] Dubowitz Neuromuscular Ctr, London, England.
   [Morrison, Leslie A.] Univ New Mexico, Sch Med, Albuquerque, NM 87131 USA.
   [Schuler, Pamela M.] Univ Florida, Gainesville, FL USA.
   [Storhaug, Kari] Natl Resource Ctr Oral Hlth Rare Med Condit, Oslo, Norway.
   [Vainzof, Mariz] Univ Sao Paulo, Sao Paulo, Brazil.
RP Wang, CH (reprint author), Stanford Univ, Med Ctr, Dept Neurol & Neurol Sci, Div Child Neurol, 750 Welch Rd,Suite 317, Palo Alto, CA 94304 USA.
EM ching.wang11@gmail.com
RI Vainzof, Mariz/J-7150-2012; Jungbluth, Heinz/B-8893-2012; North,
   Kathryn/K-6476-2012; 
OI Bertini, Enrico/0000-0001-9276-4590; Vainzof, Mariz/0000-0002-2797-0782;
   Sejersen, Thomas/0000-0001-5961-7097; North,
   Kathryn/0000-0003-0841-8009; Morrison, Leslie/0000-0002-0092-193X;
   Koumbourlis, Anastassios/0000-0002-4400-4885; Connolly,
   Anne/0000-0002-9193-2457
FU A Foundation Building Strength; TREAT-NMD
FX The authors disclosed receipt of the following financial support for the
   research, authorship and/or publication of this article: This project is
   supported by grants from A Foundation Building Strength
   (www.buildingstrength.org) and TREAT-NMD (www.treat-nmd.edu).
NR 108
TC 33
Z9 33
U1 0
U2 6
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0883-0738
J9 J CHILD NEUROL
JI J. Child Neurol.
PD MAR
PY 2012
VL 27
IS 3
BP 363
EP 382
DI 10.1177/0883073812436605
PG 20
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA 912JO
UT WOS:000301794400011
PM 22431881
ER

PT J
AU Lopes, M
   Olfson, M
   Rabkin, J
   Hasin, DS
   Alegria, AA
   Lin, KH
   Grant, BF
   Blanco, C
AF Lopes, Mariana
   Olfson, Mark
   Rabkin, Judith
   Hasin, Deborah S.
   Alegria, Analucia A.
   Lin, Keng-Han
   Grant, Bridget F.
   Blanco, Carlos
TI Gender, HIV Status, and Psychiatric Disorders: Results From the National
   Epidemiologic Survey on Alcohol and Related Conditions
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Article
ID INJECTION-DRUG USERS; ACTIVE ANTIRETROVIRAL THERAPY; INTERVIEW SCHEDULE
   AUDADIS; GENERAL-POPULATION SAMPLE; DSM-IV ALCOHOL; COMORBIDITY SURVEY
   REPLICATION; RANDOMIZED CONTROLLED-TRIALS; PERSISTENT MENTAL-ILLNESS;
   SUBSTANCE USE DISORDERS; UNITED-STATES
AB Objective: More than 30 years after the onset of the human immunodeficiency virus (HIV) epidemic, there is no information on the prevalence of psychiatric disorders among HIV-positive individuals in the general population. We sought to compare the prevalence of 12-month psychiatric disorders among HIV-positive and HIV-negative adults stratified by sex and to examine the differential increase in risk of a psychiatric disorder as a function of the interaction of sex and HIV status.
   Method: Face-to-face interviews were conducted between 2004 and 2005 with participants in the National Epidemiologic Survey on Alcohol and Related Conditions Wave 2, a large nationally representative sample of US adults (34,653). The diagnostic interview used was the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version.
   Results: When compared with their HIV-negative same-sex counterparts, HIV-positive men were more likely to have any mood disorder (odds ratio [OR] =6.10; 95% confidence interval [Cl], 2.99-12.44), major depressive disorder/dysthymia (OR= 3.77; 95% CI, 1.16-12.27), any anxiety disorder (OR =4.02; 95% CI, 2.12-7.64), and any personality disorder (OR= 2.50; 95% CI, 1.34-4.67). In relation to their same-sex HIV-negative counterparts, the effect of HIV status on the odds of any mood disorder (OR= 7.17; 95% CI, 2.52-20.41), any anxiety disorder (OR = 3.45; 95% CI, 1.27-9.38), and any personality disorder (OR = 2.66; 95% CI, 1.16-6.10) was significantly greater for men than women.
   Conclusions: HIV status was significantly more strongly associated with psychiatric disorders in men than in women. HIV-positive men had a higher prevalence than HIV-negative men of most psychiatric disorders. By contrast, HIV-positive women were not significantly more likely than HIV-negative women to have psychiatric disorders. J Clin Psychiatry 2012;73(3):384-391 (C) Copyright 2011 Physicians Postgraduate Press, Inc.
C1 [Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA.
   [Lopes, Mariana; Olfson, Mark; Rabkin, Judith; Hasin, Deborah S.; Alegria, Analucia A.; Lin, Keng-Han; Blanco, Carlos] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
   [Olfson, Mark; Rabkin, Judith; Hasin, Deborah S.; Blanco, Carlos] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA.
   [Hasin, Deborah S.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.
RP Grant, BF (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Room 3077,MS 9304,5635 Fishers Lane, Bethesda, MD 20892 USA.
EM bgrant@willco.niaaa.nih.gov
RI Blanco, Carlos/I-4906-2013; 
OI Blanco, Carlos/0000-0001-6187-3057; Alegria, Analucia
   /0000-0001-6044-3311
FU GlaxoSmithKline; Eli Lilly; Pfizer; Bristol-Myers Squibb; National
   Epidemiologic Survey on Alcohol and Related Conditions; National
   Institute on Alcohol Abuse and Alcoholism (NIAAA); Intramural Program;
   NIAAA; National Institutes of Health (NIH) [DA019606, DA020783,
   DA023200, DA023973, MH076051, P60 MD00020, R01 AA08159, K05AA00161];
   American Foundation for Suicide Prevention; New York State Psychiatric
   Institute
FX Dr Blanco has received research support from GlaxoSmithKline, Eli Lilly,
   and Pfizer. Dr Olfson has received research support from Bristol-Myers
   Squibb and Eli Lilly. The remaining authors report no potential conflict
   of interest.; The National Epidemiologic Survey on Alcohol and Related
   Conditions was sponsored by the National Institute on Alcohol Abuse and
   Alcoholism (NIAAA) and funded, in part, by the Intramural Program,
   NIAAA, National Institutes of Health (NIH). This study is supported by
   NIH grants DA019606, DA020783, DA023200, DA023973, and MH076051 (Dr
   Blanco); P60 MD000206 (Dr Olfson); R01 AA08159 and K05AA00161 (Dr
   Hasin); the American Foundation for Suicide Prevention (Dr Blanco); and
   the New York State Psychiatric Institute (Drs Blanco, Olfson, Rabkin,
   and Hasin).
NR 82
TC 28
Z9 28
U1 4
U2 14
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 MAR
PY 2012
VL 73
IS 3
BP 384
EP 391
DI 10.4088/JCP.10m06304
PG 8
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 916OV
UT WOS:000302114000017
PM 22053858
ER

PT J
AU Gao, B
AF Gao, Bin
TI Hepatoprotective and anti-inflammatory cytokines in alcoholic liver
   disease
SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Article
DE alcoholic liver disease; interleukin-6; interleukin-10; interleukin-22
ID SIGNAL TRANSDUCER; TRANSCRIPTION 3; HEPATIC STEATOSIS; INJURY;
   INTERLEUKIN-22; MICE; PATHOGENESIS; IL-22; STAT3; ACTIVATOR
AB The activation of innate immunity by various factors (e.g. lipopolysaccharide and complements) plays an important role in initiating and promoting alcoholic liver injury via the stimulation of Kupffer cells to induce oxidative stress and to produce pro-inflammatory cytokines (e.g. tumor necrosis factor [TNF]-alpha) that cause hepatocellular damage. Accumulating evidence suggests that the activation of innate immunity also stimulates Kupffer cells to produce the hepatoprotective cytokine interleukin-6 (IL-6) and the anti-inflammatory cytokine IL-10 during alcoholic liver injury. IL-6 protects against alcoholic liver injury via the activation of signal transducer and activator of transcription 3 (STAT3) and the subsequent induction of a variety of hepatoprotective genes in hepatocytes. IL-10 inhibits alcoholic liver inflammation via the activation of STAT3 in Kupffer cells/macrophages and the subsequent inhibition of liver inflammation. Recent studies have suggested that IL-10 may play a dual role in controlling ethanol-induced steatosis and liver injury via the inhibition of the pro-inflammatory cytokine TNF-alpha, thereby ameliorating alcoholic liver injury, or via the inhibition of the hepatoprotective cytokine IL-6, thereby potentiating alcoholic liver injury. IL-22 is another important hepatoprotective cytokine that protects against acute and chronic alcoholic liver injury by binding to a receptor complex composed of IL-10R2 and IL-22R chains on the surfaces of hepatocytes. Finally, IL-22 treatment is a potential therapeutic option for treating severe forms of alcoholic liver disease because of its antioxidant, antiapoptotic, antisteatotic, proliferative, and antimicrobial effects, as well as the potential added benefit of few side effects.
C1 NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA.
RP Gao, B (reprint author), NIAAA, Lab Liver Dis, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA.
EM bgao@mail.nih.gov
FU Intramural NIH HHS [Z99 AA999999, ZIA AA000369-10]
NR 44
TC 60
Z9 60
U1 0
U2 15
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0815-9319
J9 J GASTROEN HEPATOL
JI J. Gastroenterol. Hepatol.
PD MAR
PY 2012
VL 27
SU 2
SI SI
BP 89
EP 93
DI 10.1111/j.1440-1746.2011.07003.x
PG 5
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 889AX
UT WOS:000300047000018
PM 22320924
ER

PT J
AU Crespo, LG
   Matsutani, M
   Annaswamy, AM
AF Crespo, Luis G.
   Matsutani, Megumi
   Annaswamy, Anuradha M.
TI Design of an Adaptive Controller for a Remotely Operated Air Vehicle
SO JOURNAL OF GUIDANCE CONTROL AND DYNAMICS
LA English
DT Article
AB This paper presents an augmented control architecture for safe flight. This architecture consists of a nominal controller that provides satisfactory performance under nominal flying conditions and a direct model reference adaptive controller that provides robustness to parametric uncertainty. The design, implementation, tuning, and robustness analysis procedures of both the nominal and augmented controllers are presented. The aim of these procedures, which encompass both theoretical and practical considerations, is to develop a controller suitable for flight. The architecture proposed is applied to the NASA generic transport model. This is a model of a transport aircraft for which both a dynamically scaled flight-test article and a high-fidelity simulation are available. A robustness analysis framework, which bounds the set of adverse flying conditions for which all closed-loop requirements are met, indicates some advantages and drawbacks of adaptation. The adverse conditions considered are grouped into four categories: aerodynamic uncertainties, structural damage, unknown time delays, and actuator failures. These failures include partial and total loss of control effectiveness, locked-in-place control surface deflections, and engine-out conditions. The requirements are fast pilot-command tracking, bounded structural loading, satisfactory transient response, bounded flight envelope, and satisfactory handling/riding qualities. A computational approach that integrates this robustness analysis framework and a design-optimization technique is proposed. This approach enables the systematic search for the controller's parameters that yield the best robustness characteristics allowed by the control structure.
C1 [Crespo, Luis G.] NIA, Hampton, VA 23666 USA.
   [Matsutani, Megumi] MIT, Dept Aeronaut & Astronaut, Cambridge, MA 02139 USA.
RP Crespo, LG (reprint author), NIA, 100 Explorat Way, Hampton, VA 23666 USA.
NR 17
TC 4
Z9 4
U1 0
U2 2
PU AMER INST AERONAUT ASTRONAUT
PI RESTON
PA 1801 ALEXANDER BELL DRIVE, STE 500, RESTON, VA 22091-4344 USA
SN 0731-5090
J9 J GUID CONTROL DYNAM
JI J. Guid. Control Dyn.
PD MAR-APR
PY 2012
VL 35
IS 2
BP 406
EP 422
DI 10.2514/1.54779
PG 17
WC Engineering, Aerospace; Instruments & Instrumentation
SC Engineering; Instruments & Instrumentation
GA 910IT
UT WOS:000301631100006
ER

PT J
AU Bolzani, VD
   Davies-Coleman, M
   Newman, DJ
   Singh, SB
AF Bolzani, Vanderlan da Silva
   Davies-Coleman, Michael
   Newman, David J.
   Singh, Sheo B.
TI Gordon M. Cragg, D.Phil., D.Sc. (h.c.): A Man for All Natural Products
SO JOURNAL OF NATURAL PRODUCTS
LA English
DT Editorial Material
ID AGENTS
C1 [Bolzani, Vanderlan da Silva] Sao Paulo State Univ Araraquara, Sao Paulo, Brazil.
   [Davies-Coleman, Michael] Rhodes Univ, ZA-6140 Grahamstown, South Africa.
   [Newman, David J.] NCI, Nat Prod Branch, Frederick, MD 21701 USA.
   [Singh, Sheo B.] Merck Res Labs, Rahway, NJ USA.
RP Bolzani, VD (reprint author), Sao Paulo State Univ Araraquara, Sao Paulo, Brazil.
RI Bolzani, Vanderlan/C-2111-2012
OI Bolzani, Vanderlan/0000-0001-7019-5825
NR 3
TC 1
Z9 1
U1 0
U2 8
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0163-3864
J9 J NAT PROD
JI J. Nat. Prod.
PD MAR
PY 2012
VL 75
IS 3
BP 309
EP 310
DI 10.1021/np201003c
PG 2
WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy
GA 912OY
UT WOS:000301810700001
ER

PT J
AU Newman, DJ
   Cragg, GM
AF Newman, David J.
   Cragg, Gordon M.
TI Natural Products As Sources of New Drugs over the 30 Years from 1981 to
   2010
SO JOURNAL OF NATURAL PRODUCTS
LA English
DT Review
ID DIVERSITY-ORIENTED SYNTHESIS; CHROMOBACTERIUM-VIOLACEUM NO-968; AT(2)
   RECEPTOR; BIOLOGICAL-PROPERTIES; MULTIPLE-SCLEROSIS; ANTITUMOR-ACTIVITY;
   FINGOLIMOD FTY720; CHEMICAL SPACE; SHIKIMIC ACID; MARKET
AB This review is an updated and expanded version of the three prior reviews that were published in this journal in 1997, 2003, and 2007. In the case of all approved therapeutic agents, the time frame has been extended to cover the 30 years from January 1, 1981, to December 31, 2010, for all diseases worldwide, and from 1950 (earliest so far identified) to December 2010 for all approved antitumor drugs worldwide. We have continued to utilize our secondary subdivision of a "natural product mimic" or "NM" to join the original primary divisions and have added a new designation, "natural product botanical" or "NB", to cover those botanical "defined mixtures" that have now been recognized as drug entities by the FDA and similar organizations. From the data presented, the utility of natural products as sources of novel structures, but not necessarily the final drug entity, is still alive and well. Thus, in the area of cancer, over the time frame from around the 1940s to date, of the 175 small molecules, 131, or 74.8%, are other than "S" (synthetic), with 85, or 48.6%, actually being either natural products or directly derived therefrom. In other areas, the influence of natural product structures is quite marked, with, as expected from prior information, the anti-infective area being dependent on natural products and their structures. Although combinatorial chemistry techniques have succeeded as methods of optimizing structures and have been used very successfully in the optimization of many recently approved agents, we are able to identify only one de novo combinatorial compound approved as a drug in this 30-year time frame. We wish to draw the attention of readers to the rapidly evolving recognition that a significant number of natural product drugs/leads are actually produced by microbes and/or microbial interactions with the "host from whence it was isolated", and therefore we consider that this area of natural product research should be expanded significantly.
C1 [Newman, David J.; Cragg, Gordon M.] NCI, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA.
RP Newman, DJ (reprint author), NCI, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag, POB B, Frederick, MD 21702 USA.
EM newmand@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 142
TC 1609
Z9 1663
U1 74
U2 794
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0163-3864
EI 1520-6025
J9 J NAT PROD
JI J. Nat. Prod.
PD MAR
PY 2012
VL 75
IS 3
BP 311
EP 335
DI 10.1021/np200906s
PG 25
WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy
GA 912OY
UT WOS:000301810700002
PM 22316239
ER

PT J
AU Pettit, GR
   Rosenberg, HJ
   Dixon, R
   Knight, JC
   Hamel, E
   Chapuis, JC
   Pettit, RK
   Hogan, F
   Sumner, B
   Ain, KB
   Trickey-Platt, B
AF Pettit, George R.
   Rosenberg, Heidi J.
   Dixon, Rachel
   Knight, John C.
   Hamel, Ernest
   Chapuis, Jean-Charles
   Pettit, Robin K.
   Hogan, Fiona
   Sumner, Brandy
   Ain, Kenneth B.
   Trickey-Platt, Brindi
TI Antineoplastic Agents. 548. Synthesis of lodo- and Diiodocombstatin
   Phosphate Prodrugs
SO JOURNAL OF NATURAL PRODUCTS
LA English
DT Article
ID COMBRETASTATIN A4 PHOSPHATE; VASCULAR DISRUPTING AGENTS; TUMOR
   BLOOD-FLOW; STRUCTURAL MODIFICATIONS; BIOLOGICAL EVALUATION;
   THYROID-CANCER; PHASE-I; ANTICANCER ACTIVITY; A-4 PRODRUG; CELL-LINES
AB Toward the objective of designing a structurally modified analogue of the combretastatin A-4 phosphate prodrug (1b) with the potential for increased specificity toward thyroid carcinoma, synthesis of a series of iodocombstatin phosphate (11a-h) and diiodocombstatin phosphate prodrugs (12a-h) has been accomplished. The diiodo series was obtained via 8a and 9c from condensation of 4 and 6, and the iodo sequence involved a parallel pathway. Both series of iodocombstatins were found to display significant to powerful inhibition of the growth of a panel of human cancer cell lines and of the murine P388 lymphocytic leukemia cell line. Of the diiodo series, 12a was also found to markedly inhibit growth of pediatric neuroblastoma, and monoiodocombstatin 9a strongly inhibited HUVEC growth. Overall, the strongest activity was found against the breast, CNS, leukemia, lung, and prostate cancer cell lines and the least activity against the pancreas and colon lines. Parallel biological investigations of tubulin interaction, antiangiogenesis, and antimicrobial effects were also conducted.
C1 [Pettit, George R.; Rosenberg, Heidi J.; Dixon, Rachel; Knight, John C.; Chapuis, Jean-Charles; Pettit, Robin K.; Hogan, Fiona; Sumner, Brandy; Trickey-Platt, Brindi] Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA.
   [Pettit, George R.; Rosenberg, Heidi J.; Dixon, Rachel; Knight, John C.; Chapuis, Jean-Charles; Pettit, Robin K.; Hogan, Fiona; Sumner, Brandy; Trickey-Platt, Brindi] Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA.
   [Hamel, Ernest] NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA.
   [Ain, Kenneth B.] Univ Kentucky, Med Ctr, Dept Internal Med, Div Endocrinol & Mol Med, Lexington, KY 40536 USA.
RP Pettit, GR (reprint author), Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA.
EM bpettit@asu.edu
FU Division of Cancer Treatment and Diagnosis, National Cancer Institute,
   DHHS [RO1 CA90441-01-04, 2R56-CA 09441-06A1, 5R01 CA 090441-07]; Arizona
   Disease Control Research Commission; Robert S. Dalton Endowment Fund; J.
   W. Kieckhefer Foundation; Margaret T. Morris Foundation; Caitlin Robb
   Foundation
FX We appreciate the financial support provided by grants RO1
   CA90441-01-04, 2R56-CA 09441-06A1, and 5R01 CA 090441-07 awarded by the
   Division of Cancer Treatment and Diagnosis, National Cancer Institute,
   DHHS; the Arizona Disease Control Research Commission; the Robert S.
   Dalton Endowment Fund; Dr. Alec D. Keith; the J. W. Kieckhefer
   Foundation; the Margaret T. Morris Foundation; the Caitlin Robb
   Foundation; and Dr. J. C. Budzinski. For other helpful assistance, we
   thank Drs. J. M. Schmidt, M. D. Minardi, and M. P. Grealish, as well as
   C. Weber, M. J. Dodson, F. Craciunescu, and L. Williams.
NR 55
TC 6
Z9 6
U1 0
U2 8
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0163-3864
EI 1520-6025
J9 J NAT PROD
JI J. Nat. Prod.
PD MAR
PY 2012
VL 75
IS 3
BP 385
EP 393
DI 10.1021/np200797x
PG 9
WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy
GA 912OY
UT WOS:000301810700009
PM 22324723
ER

PT J
AU Whitson, EL
   Sun, H
   Thomas, CL
   Henrich, CJ
   Sayers, TJ
   McMahon, JB
   Griesinger, C
   Mckee, TC
AF Whitson, Emily L.
   Sun, Han
   Thomas, Cheryl L.
   Henrich, Curtis J.
   Sayers, Thomas J.
   McMahon, James B.
   Griesinger, Christian
   McKee, Tawnya C.
TI Synergistic TRAIL Sensitizers from Barleria alluaudii and Diospyros
   maritima
SO JOURNAL OF NATURAL PRODUCTS
LA English
DT Article
ID DENSITY-FUNCTIONAL THEORY; ABSOLUTE-CONFIGURATION; DEATH RECEPTORS;
   NAPHTHOQUINONE DERIVATIVES; CIRCULAR-DICHROISM; ANTICANCER AGENTS;
   OPTICAL-ROTATION; NATURAL-PRODUCTS; CANCER-THERAPY; MECHANISMS
AB Barleria alluaudii and Diospyros maritima were both investigated as part of an ongoing search for synergistic TRAIL (tumor necrosis factor-alpha-related apoptosis-inducing ligand) sensitizers. As a result of this study, two naphthoquinone epoxides, 2,3-epoxy-2,3-dihydrolapachol (1) and 2,3-epoxy-2,3-dihydro-8-hydroxylapachol (2), both not previously isolated from natural sources, and the known 2-methylanthraquinone (3) were identified from B. alluaudii. Time-dependent density functional theory (TD-DFT) calculations of electronic circular dichroism (ECD) spectra were utilized to establish the absolute configuration of 1 and 2. Additionally, five known naphthoquinone derivatives, maritinone (4), elliptinone (5), plumbagin (6), (+)-cis-isoshinanolone (7), and ethylidene-6,6'-biplumbagin (8), were isolated from D. maritima. Compounds 1, 2, and 4-6 showed varying levels of synergy with TRAIL. Maritinone (4) and elliptinone (5) showed the highest synergistic effect, with more than a 3-fold increase in activity observed with TRAIL than with compound alone.
C1 [Whitson, Emily L.; Thomas, Cheryl L.; Henrich, Curtis J.; McMahon, James B.; McKee, Tawnya C.] NCI Frederick, Mol Targets Lab, Mol Discovery Program, Ctr Canc Res, Frederick, MD 21702 USA.
   [Sun, Han; Griesinger, Christian] Max Planck Inst Biophys Chem, Dept NMR Based Struct Biol, D-37077 Gottingen, Germany.
   [Henrich, Curtis J.; Sayers, Thomas J.] SAIC Frederick Inc, Frederick, MD 21702 USA.
   [Sayers, Thomas J.] NCI Frederick, Expt Immunol Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.
RP Mckee, TC (reprint author), NCI Frederick, Mol Targets Lab, Mol Discovery Program, Ctr Canc Res, Frederick, MD 21702 USA.
EM mckeeta@mail.nih.gov
RI Sayers, Thomas/G-4859-2015
FU NIH, National Cancer Institute, Center for Cancer Research; National
   Cancer Institute, National Institutes of Health [HHSN261200800001E]; Max
   Planck Society; Deutsche Forschungsgemeinschaft [GRK 782, FOR 934];
   Fonds der Chemischen Industrie
FX The authors thank J. A. McDonald & Afriastini for collection and J. A.
   McDonald for taxonomic identification of D. maritima (N053469) as part
   of the collection contract with D. D. Soejarto (UIC) and J. Zarucchi, E.
   Rakotobe, A. Randrianasolo, and A. Poole for collection and J. Zarucchi
   for taxonomic identification of B. alluaudii (N037953) as part of the
   collection contract with J. Miller (MO Botanical Garden). The authors
   also thank D. Newman (NPB) for collection and contract administration,
   T. McCloud and the Natural Products Support Laboratory for plant
   extractions, S. Tarasov and M. Dyba of the Biophysics Resource of the
   Structural Biophysics Laboratory for providing technical assistance with
   Q-TOF LC-MS experiments and ECD experiments, and M. P. McCoy of
   Phenomenex for chiral HPLC analysis. This research was supported in part
   by the Intramural Research Program of NIH, National Cancer Institute,
   Center for Cancer Research. This project has been funded in part with
   federal funds from the National Cancer Institute, National Institutes of
   Health, under contract HHSN261200800001E. The content of this
   publication does not necessarily reflect the views or policies of the
   Department of Health and Human Services, nor does mention of trade
   names, commercial products, or organizations imply endorsement by the
   U.S. Government. C.G. thanks the Max Planck Society, the Deutsche
   Forschungsgemeinschaft (GRK 782 and FOR 934), and the Fonds der
   Chemischen Industrie for financial support.
NR 38
TC 10
Z9 10
U1 1
U2 7
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0163-3864
J9 J NAT PROD
JI J. Nat. Prod.
PD MAR
PY 2012
VL 75
IS 3
BP 394
EP 399
DI 10.1021/np200805z
PG 6
WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy
GA 912OY
UT WOS:000301810700010
PM 22313254
ER

PT J
AU Akee, RK
   Ransom, T
   Ratnayake, R
   McMahon, JB
   Beutler, JA
AF Akee, Rhone K.
   Ransom, Tanya
   Ratnayake, Ranjala
   McMahon, James B.
   Beutler, John A.
TI Chlorinated Englerins with Selective Inhibition of Renal Cancer Cell
   Growth
SO JOURNAL OF NATURAL PRODUCTS
LA English
DT Article
ID (-)-ENGLERIN; CHLOROFORM
AB The chlorinated englerins (3-9) were isolated from Phyllanthus engleri and shown to selectively inhibit the growth of renal cancer cells. The compounds were shown to be extraction artifacts produced by exposure to chloroform decomposition products during their isolation. The most active compound, 3, was synthesized from englerin A (1).
C1 [Ransom, Tanya; Ratnayake, Ranjala; McMahon, James B.; Beutler, John A.] NCI, Mol Targets Lab, Mol Discovery Program, Ctr Canc Res, Frederick, MD 21702 USA.
   [Akee, Rhone K.] SAIC Frederick Natl Canc Inst, Nat Prod Support Grp, Frederick, MD 21702 USA.
RP Beutler, JA (reprint author), NCI, Mol Targets Lab, Mol Discovery Program, Ctr Canc Res, Frederick, MD 21702 USA.
EM beutlerj@mail.nih.gov
RI Beutler, John/B-1141-2009
OI Beutler, John/0000-0002-4646-1924
FU National Cancer Institute, National Institutes of Health
   [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer
   Research; Division of Cancer Treatment and Diagnosis of the National
   Cancer Institute
FX This project has been funded in whole or in part with federal funds from
   the National Cancer Institute, National Institutes of Health, under
   Contract No. HHSN261200800001E. This research was supported, in part,
   both by the Intramural Research Program of the NIH, National Cancer
   Institute, Center for Cancer Research, and, in part, by the
   Developmental Therapeutics Program in the Division of Cancer Treatment
   and Diagnosis of the National Cancer Institute. 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. We gratefully acknowledge J. Schneider and P. Grothaus
   for helpful comments, and H. Bokesch (MTL), S. Tarasov, and M. Dyba
   (Biophysics Resource Core, Structural Biophysics Laboratory, CCR) for
   acquiring high-resolution mass spectra.
NR 16
TC 18
Z9 18
U1 0
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0163-3864
J9 J NAT PROD
JI J. Nat. Prod.
PD MAR
PY 2012
VL 75
IS 3
BP 459
EP 463
DI 10.1021/np200905u
PG 5
WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy
GA 912OY
UT WOS:000301810700019
PM 22280462
ER

PT J
AU McClain, JJ
   Grant, D
   Willis, G
   Berrigan, D
AF McClain, James J.
   Grant, David
   Willis, Gordon
   Berrigan, David
TI Effect of Temporal Domain on Self-Reported Walking Behaviors in the
   California Health Interview Survey
SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH
LA English
DT Article
DE physical activity; assessment; survey methodology; transportation;
   leisure
ID OF-SPORTS-MEDICINE; PHYSICAL-ACTIVITY; ACTIVITY RECOMMENDATIONS;
   PUBLIC-HEALTH; PREVALENCE; DISEASE
AB Background: Question design can influence the validity and reliability of physical activity (PA) self-report instruments. This study assesses the effect of temporal domain ("days" walked versus "times" walked) on survey questions about walking behavior. Methods: A 2005 California Health Interview Survey (CHIS) sub-sample (n = 6332) reported the number of days or times they walked for leisure or transportation in the past 7 days and the usual time spent per day or per time. Question order was randomized by temporal domain. Minutes walked per week (mean +/- SE) and adherence to PA guidelines (>= 150 min/wk) were assessed. Results: Estimates of leisure walking remained stable across temporal domain (days = 71.4 +/- 2.5 min; times = 73.4 +/- 2.4 min), but transportation walking differed depending on domain (days = 70.4 +/- 3.2 min; times = 52.5 +/- 2.6 min). Adherence to PA guidelines based on leisure walking was stable across temporal domain (days = 14.9 +/- 0.6%; times = 14.9 +/- 0.6%), but again differed by domain for transportation walking (days = 10.4 +/- 0.6%; times = 7.8 +/- 0.5%). A large order effect (number-of-days versus number-of-times asked first) was observed for reports of days walking for transportation (days first = 87.8 +/- 2.9 min; times first = 52.3 +/- 2.5 min). Conclusion: Temporal domain influences estimates of self-reported transportation walking behavior. Current efforts to capture PA from both transportation and leisure activities in health research appear to present distinct methodological challenges.
C1 [McClain, James J.] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA.
   [Grant, David] Univ Calif Los Angeles, Calif Hlth Interview Survey, Los Angeles, CA USA.
   [Willis, Gordon; Berrigan, David] NCI, Appl Res Program, Bethesda, MD 20892 USA.
RP McClain, JJ (reprint author), NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA.
NR 13
TC 3
Z9 3
U1 0
U2 0
PU HUMAN KINETICS PUBL INC
PI CHAMPAIGN
PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA
SN 1543-3080
J9 J PHYS ACT HEALTH
JI J. Phys. Act. Health
PD MAR
PY 2012
VL 9
IS 3
BP 344
EP 351
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 916MB
UT WOS:000302106800003
PM 21934160
ER

PT J
AU Myers, SL
   Baird, DD
   Olshan, AF
   Herring, AH
   Schroeder, JC
   Nylander-French, LA
   Hartmann, KE
AF Myers, Sharon L.
   Baird, Donna Day
   Olshan, Andrew F.
   Herring, Amy H.
   Schroeder, Jane C.
   Nylander-French, Leena A.
   Hartmann, Katherine E.
TI Self-Report Versus Ultrasound Measurement of Uterine Fibroid Status
SO JOURNAL OF WOMENS HEALTH
LA English
DT Article
ID WHITE WOMEN; LEIOMYOMATA; PREGNANCY; GROWTH; AGE; SYMPTOMATOLOGY;
   REGRESSION; DIAGNOSIS; ETIOLOGY; MYOMAS
AB Background: Much of the epidemiologic research on risk factors for fibroids, the leading indication for hysterectomy, relies on self-reported outcome. Self-report is subject to misclassification because many women with fibroids are undiagnosed. The purpose of this analysis was to quantify the extent of misclassification and identify associated factors.
   Methods: Self-reported fibroid status was compared to ultrasound screening from 2046 women in Right From The Start (RFTS) and 869 women in the Uterine Fibroid Study (UFS). Log-binomial regression was used to estimate sensitivity (Se) and specificity (Sp) and examine differences by ethnicity, age, education, body mass index, parity, and miscarriage history.
   Results: Overall sensitivity was <= 0.50. Sensitivity was higher in blacks than whites (RFTS: 0.34 vs. 0.23; UFS: 0.58 vs. 0.32) and increased with age. Parous women had higher sensitivity than nulliparae, especially in RFTS whites (Se ratio = 2.90; 95% confidence interval [CI]: 1.51, 5.60). Specificity was 0.98 in RFTS and 0.86 in UFS. Modest ethnic differences were seen in UFS (Sp ratio, black vs. white = 0.90; 95% CI: 0.81, 0.99). Parity was inversely associated with specificity, especially among UFS black women (Sp ratio = 0.84; 95% CI: 0.73, 0.97). Among women who reported a previous diagnosis, a shorter time interval between diagnosis and ultrasound was associated with increased agreement between the two measures.
   Conclusions: Misclassification of fibroid status can differ by factors of etiologic interest. These findings are useful for assessing (and correcting) bias in studies using self-reported clinical diagnosis as the outcome measure.
C1 [Myers, Sharon L.; Olshan, Andrew F.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
   [Myers, Sharon L.; Baird, Donna Day] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA.
   [Herring, Amy H.] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA.
   [Herring, Amy H.] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA.
   [Schroeder, Jane C.] Natl Inst Environm Hlth Sci, Morrisville, NC USA.
   [Nylander-French, Leena A.] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC USA.
   [Hartmann, Katherine E.] Vanderbilt Univ, Med Ctr, Inst Med & Publ Hlth, Nashville, TN USA.
   [Hartmann, Katherine E.] Vanderbilt Univ, Med Ctr, Dept Obstet & Gynecol, Nashville, TN 37232 USA.
RP Myers, SL (reprint author), Univ Calif, Dept Publ Hlth Sci, Sch Med, 3700 Business Dr,Suite 130, Sacramento, CA 95820 USA.
EM slmyers@ucdavis.edu
RI Baird, Donna/D-5214-2017
OI Baird, Donna/0000-0002-5544-2653
FU National Institute of Environmental Health Sciences at the National
   Institutes of Health [P30ES10126]; National Institute of Child Health
   and Human Development [R01HD043883, R01HD049675]
FX This work was supported in part by the intramural research program of
   the National Institute of Environmental Health Sciences at the National
   Institutes of Health. Right From The Start was supported in part by
   grants from the National Institute of Child Health and Human Development
   (R01HD043883 and R01HD049675) and the National Institute of
   Environmental Health Sciences (P30ES10126) at the National Institutes of
   Health. The authors thank Dr. Aimee D'Aloisio and Dr. Todd Jusko for
   their comments on an earlier version of this manuscript, and Dr. Sue
   Edelstein for help with graphics.
NR 25
TC 16
Z9 16
U1 0
U2 4
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-9996
J9 J WOMENS HEALTH
JI J. Womens Health
PD MAR
PY 2012
VL 21
IS 3
BP 285
EP 293
DI 10.1089/jwh.2011.3008
PG 9
WC Public, Environmental & Occupational Health; Medicine, General &
   Internal; Obstetrics & Gynecology; Women's Studies
SC Public, Environmental & Occupational Health; General & Internal
   Medicine; Obstetrics & Gynecology; Women's Studies
GA 905SD
UT WOS:000301292700006
PM 22044079
ER

PT J
AU Schiffenbauer, AI
   Wahl, C
   Pittaluga, S
   Jaffe, ES
   Hoffman, R
   Khosroshahi, A
   Stone, JH
   Deshpande, V
   Gahl, WA
   Gill, F
AF Schiffenbauer, Adam I.
   Wahl, Colleen
   Pittaluga, Stefania
   Jaffe, Elaine S.
   Hoffman, Ronald
   Khosroshahi, Arezou
   Stone, John H.
   Deshpande, Vikram
   Gahl, William A.
   Gill, Fred
TI IgG4-related disease presenting as recurrent mastoiditis
SO LARYNGOSCOPE
LA English
DT Editorial Material
ID SYSTEMIC-DISEASE; SCLEROSING DISEASE
C1 [Wahl, Colleen; Gahl, William A.; Gill, Fred] NHGRI, NIH, Undiagnosed Dis Program, Bethesda, MD 20892 USA.
   [Pittaluga, Stefania; Jaffe, Elaine S.] NHGRI, Pathol Lab, Ctr Clin, NIH, Bethesda, MD 20892 USA.
   [Gill, Fred] NHGRI, Internal Med Consult Serv, Ctr Clin, NIH, Bethesda, MD 20892 USA.
   [Gahl, William A.] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA.
   [Schiffenbauer, Adam I.] NIAMSD, NIH, Bethesda, MD 20892 USA.
   [Hoffman, Ronald] New York Eye & Ear Infirm, Ear Inst, New York, NY 10003 USA.
   [Khosroshahi, Arezou; Stone, John H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Rheumatol Unit, Boston, MA USA.
   [Deshpande, Vikram] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
RP Schiffenbauer, AI (reprint author), NIH, Ctr Clin, Bldg 10,Room 6N216A,10 Ctr Dr, Bethesda, MD 20892 USA.
EM adam.schiffenbauer@nih.gov
OI Jaffe, Elaine/0000-0003-4632-0301; Schiffenbauer,
   Adam/0000-0001-9964-9966
FU Intramural NIH HHS [Z99 AR999999]
NR 12
TC 15
Z9 16
U1 1
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0023-852X
J9 LARYNGOSCOPE
JI Laryngoscope
PD MAR
PY 2012
VL 122
IS 3
BP 681
EP 684
DI 10.1002/lary.22486
PG 4
WC Medicine, Research & Experimental; Otorhinolaryngology
SC Research & Experimental Medicine; Otorhinolaryngology
GA 897TN
UT WOS:000300680200033
PM 22252885
ER

PT J
AU Tom, SE
   Cooper, R
   Patel, KV
   Guralnik, JM
AF Tom, Sarah E.
   Cooper, Rachel
   Patel, Kushang V.
   Guralnik, Jack M.
TI Menopausal characteristics and physical functioning in older adulthood
   in the National Health and Nutrition Examination Survey III
SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
LA English
DT Article
DE Menopause; Physical functioning; Women's health
ID BRITISH BIRTH COHORT; HORMONE REPLACEMENT THERAPY; ISOMETRIC MUSCLE
   STRENGTH; NATURAL MENOPAUSE; POSTMENOPAUSAL WOMEN; AGE; PERFORMANCE;
   MORTALITY; HYSTERECTOMY; PERCENTAGE
AB Objective: We hypothesized that natural menopause would be related to better physical functioning compared with surgical menopause and that later age at menopause would be related to better physical functioning.
   Methods: Our sample comprised 1,765 women 60 years or older who participated in the National Health and Nutrition Examination Survey III, a cross-sectional study representative of the US population. Women recalled age at final menstrual period and age at removal of the uterus and ovaries and reported age, race and ethnicity, height, weight, educational attainment, smoking status, number of children, and use of estrogen therapy. Respondents completed a walk trial and chair rises and reported functional limitations.
   Results: Women with surgical menopause had chair rise times that were an average of 4.4% slower than did those of women with natural menopause (95% CI, 0.56-8.27). Women with natural menopause at age 55 years or more had an average walking speed of 0.05 meters/second (95% CI, 0.01-0.10) faster than did women with natural menopause at age less than 45 years. Later ages at natural and surgical menopause were also related to lower self-reported functional limitation. Women with surgical menopause at age 55 years or more had odds of functional limitation 0.52 times (95% CI, 0.29-0.95) that of women with surgical menopause at age less than 40 years, with similar patterns for natural menopause.
   Conclusions: Women with surgical menopause and earlier age at menopause had worse physical function in older adulthood. These groups of women may benefit from interventions to prevent functional decline.
C1 [Tom, Sarah E.] Univ Texas Med Branch, Dept Prevent Med & Community Hlth, Galveston, TX 77555 USA.
   [Cooper, Rachel] UCL, Med Res Council Unit Lifelong Hlth & Ageing, London, England.
   [Cooper, Rachel] UCL, Div Populat Hlth, London, England.
   [Patel, Kushang V.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
   [Guralnik, Jack M.] Univ Maryland, Sch Med, Div Gerontol, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
RP Tom, SE (reprint author), Univ Texas Med Branch, Dept Prevent Med & Community Hlth, 301 Univ Blvd, Galveston, TX 77555 USA.
EM setom@utmb.edu
OI Cooper, Rachel/0000-0003-3370-5720
FU National Institute on Aging, National Institutes of Health; National
   Institute on Aging [T32 AG027677]; New Dynamics of Ageing
   [RES-353-25-0001]; research career development award [K12HD052023]
FX This research was supported by the Intramural Research Program at the
   National Institute on Aging, National Institutes of Health and National
   Institute on Aging award T32 AG027677. Dr. Cooper is funded by the New
   Dynamics of Ageing (RES-353-25-0001). Dr. Tom, a University of Texas
   Medical Branch Building Interdisciplinary Research Careers in Women's
   Health Scholar, is supported by a research career development award
   (K12HD052023, Principal Investigator: Berenson), that is cofunded by the
   Eunice Kennedy Shriver National Institute of Child Health and Human
   Development, the Office of Research on Women's Health, and the National
   Institute of Allergy and Infectious Diseases.
NR 43
TC 7
Z9 7
U1 3
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1072-3714
J9 MENOPAUSE
JI Menopause-J. N. Am. Menopause Soc.
PD MAR
PY 2012
VL 19
IS 3
BP 283
EP 289
DI 10.1097/gme.0b013e3182292b06
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 899ZA
UT WOS:000300854000008
PM 21993081
ER

PT J
AU Natera-Naranjo, O
   Kar, AN
   Aschrafi, A
   Gervasi, NM
   Macgibeny, MA
   Gioio, AE
   Kaplan, BB
AF Natera-Naranjo, Orlangie
   Kar, Amar N.
   Aschrafi, Armaz
   Gervasi, Noreen M.
   Macgibeny, Margaret A.
   Gioio, Anthony E.
   Kaplan, Barry B.
TI Local translation of ATP synthase subunit 9 mRNA alters ATP levels and
   the production of ROS in the axon
SO MOLECULAR AND CELLULAR NEUROSCIENCE
LA English
DT Article
DE Axonal protein synthesis; mRNA translation; Axonal growth; Oxidative
   stress; Sympathetic neurons
ID SYMPATHETIC NEURONS; OXIDATIVE STRESS; OXYGEN; MITOCHONDRIAL
AB To date, it has been demonstrated that axonal mRNA populations contain a large number of nuclear-encoded mRNAs for mitochondrial proteins. Here, we report that the mRNA encoding ATP synthase subunit 9 (ATP5G1), a key component of Complex V of the oxidative phosphorylation chain, is present in the axons of rat primary sympathetic neurons, as judged by in situ hybridization and qRT-PCR methodology. Results of metabolic labeling studies establish that this nuclear-encoded mRNA is translated in the axon. The siRNA-mediated knock-down of axonal ATP5G1 mRNA resulted in a significant reduction of axonal ATP5G1 protein and ATP levels. Silencing of local ATP5G1 expression enhanced the production of local reactive oxygen species (ROS). Importantly, reduction in the levels of ATP5G1 expression resulted in a marked attenuation in the rate of elongation of the axon. Exposure of the distal axons to nordihydroguaiaretic acid (NDGA), a ROS scavenger, mitigated the reduction in the rate of axon elongation observed after knockdown of ATP5G1. Taken together, these data call attention to the key regulatory role that local translation of nuclear-encoded mitochondrial mRNAs plays in energy metabolism and growth of the axon. Published by Elsevier Inc.
C1 [Natera-Naranjo, Orlangie; Kar, Amar N.; Aschrafi, Armaz; Gervasi, Noreen M.; Macgibeny, Margaret A.; Gioio, Anthony E.; Kaplan, Barry B.] NIMH, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Kaplan, BB (reprint author), NIMH, Mol Biol Lab, NIH, Bldg 10,Room 4N-230, Bethesda, MD 20892 USA.
EM Barry.Kaplan@nih.gov
RI Aschrafi, Armaz/E-2202-2012; 
OI Kar, Amar/0000-0003-2380-7504
FU Division of Intramural Research of the National Institute of Mental
   Health
FX This work was supported by the Division of Intramural Research Programs
   of the National Institute of Mental Health. We thank Ms. Sanah Vohra for
   invaluable technical assistance.
NR 24
TC 18
Z9 18
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 1044-7431
J9 MOL CELL NEUROSCI
JI Mol. Cell. Neurosci.
PD MAR
PY 2012
VL 49
IS 3
BP 263
EP 270
DI 10.1016/j.mcn.2011.12.006
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 917TS
UT WOS:000302202100002
PM 22209705
ER

PT J
AU McNeill, B
   Perez-Iratxeta, C
   Mazerolle, C
   Furimsky, M
   Mishina, Y
   Andrade-Navarro, MA
   Wallace, VA
AF McNeill, Brian
   Perez-Iratxeta, Carol
   Mazerolle, Chantal
   Furimsky, Marosh
   Mishina, Yuji
   Andrade-Navarro, Miguel A.
   Wallace, Valerie A.
TI Comparative genomics identification of a novel set of temporally
   regulated hedgehog target genes in the retina
SO MOLECULAR AND CELLULAR NEUROSCIENCE
LA English
DT Article
DE Hedgehog; Gli transcription factors; Development; Progenitor cells;
   Retina
ID EMBRYONIC MOUSE RETINA; GLIAL-CELL DEVELOPMENT; SONIC HEDGEHOG;
   ZEBRAFISH RETINA; PROGENITOR CELLS; IN-VITRO; NR-CAM; PROLIFERATION;
   SOX9; ROLES
AB The hedgehog (Hh) signaling pathway is involved in numerous developmental and adult processes with many links to cancer. In vertebrates, the activity of the Hh pathway is mediated primarily through three Gli transcription factors (Gli1, 2 and 3) that can serve as transcriptional activators or repressors. The identification of Gli target genes is essential for the understanding of the Hh-mediated processes. We used a comparative genomics approach using the mouse and human genomes to identify 390 genes that contained conserved Gli binding sites. RT-qPCR validation of 46 target genes in E14.5 and P0.5 retinal explants revealed that Hh pathway activation resulted in the modulation of 30 of these targets, 25 of which demonstrated a temporal regulation. Further validation revealed that the expression of Bok, FoxAl, Sox8 and Wnt7a was dependent upon Sonic Hh (Shh) signaling in the retina and their regulation is under positive and negative controls by Gli2 and Gli3, respectively. We also show using chromatin immunoprecipitation that Gli2 binds to the Sox8 promoter, suggesting that Sox8 is an Hh-dependent direct target of Gli2. Finally, we demonstrate that the Hh pathway also modulates the expression of Sox9 and Sox10, which together with Sox8 make up the SoxE group. Previously, it has been shown that Hh and SoxE group genes promote Miller glial cell development in the retina. Our data are consistent with the possibility for a role of SoxE group genes downstream of Hh signaling on Muller cell development. Crown Copyright (C) 2012 Published by Elsevier Inc. All rights reserved.
C1 [McNeill, Brian; Mazerolle, Chantal; Furimsky, Marosh; Wallace, Valerie A.] Ottawa Hosp Res Inst, Vis Program, Ottawa, ON K1H 8L6, Canada.
   [Perez-Iratxeta, Carol] Ottawa Hosp Res Inst, Regenerat Med Program, Ottawa, ON K1H 8L6, Canada.
   [McNeill, Brian; Mazerolle, Chantal; Wallace, Valerie A.] Univ Ottawa, Dept Ophthalmol, Ottawa, ON K1H 8M5, Canada.
   [McNeill, Brian; Mazerolle, Chantal; Wallace, Valerie A.] Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa, ON K1H 8M5, Canada.
   [Andrade-Navarro, Miguel A.] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany.
   [Mishina, Yuji] NIEHS, Lab Reprod & Dev Toxicol, Res Triangle Pk, NC 27709 USA.
   [Mishina, Yuji] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA.
RP Wallace, VA (reprint author), Ottawa Hosp Res Inst, Vis Program, 501 Smyth Rd, Ottawa, ON K1H 8L6, Canada.
EM vwallace@ohri.ca
RI Andrade, Miguel/B-6565-2008
OI Andrade, Miguel/0000-0001-6650-1711
FU Natural Sciences and Engineering Research Council of Canada (NSERC);
   Canadian Cancer Society (National Cancer Institute of Canada) [016435]
FX We thank Alan Mears for comments on the manuscript. Brian McNeill is a
   recipient of a Natural Sciences and Engineering Research Council of
   Canada (NSERC) Doctoral Studentship. This work was supported by an
   operating grant to V. Wallace from the Canadian Cancer Society (National
   Cancer Institute of Canada Grant 016435).
NR 53
TC 11
Z9 12
U1 1
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1044-7431
J9 MOL CELL NEUROSCI
JI Mol. Cell. Neurosci.
PD MAR
PY 2012
VL 49
IS 3
BP 333
EP 340
DI 10.1016/j.mcn.2011.12.008
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 917TS
UT WOS:000302202100009
PM 22281533
ER

PT J
AU Alegre, M
   Hallett, M
   Olanow, CW
   Obeso, JA
AF Alegre, Manuel
   Hallett, Mark
   Olanow, C. Warren
   Obeso, Jose A.
TI Technical advances in deep brain stimulation: How far is enough?
SO MOVEMENT DISORDERS
LA English
DT Editorial Material
C1 [Alegre, Manuel] Univ Navarra Clin, Clin Neurophysiol Sect, Navarra 31008, Spain.
   [Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
   [Olanow, C. Warren] Mt Sinai Sch Med, Dept Neurol, New York, NY USA.
   [Olanow, C. Warren] Mt Sinai Sch Med, Dept Neurosci, New York, NY USA.
   [Obeso, Jose A.] Univ Navarra Clin, Dept Neurol, Pamplona, Spain.
RP Alegre, M (reprint author), Univ Navarra Clin, Clin Neurophysiol Sect, Pio XII 36, Navarra 31008, Spain.
EM malegre@unav.es
RI Alegre, Manuel/F-5379-2011
OI Alegre, Manuel/0000-0003-4985-9724
NR 6
TC 4
Z9 4
U1 0
U2 2
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 MAR
PY 2012
VL 27
IS 3
BP 341
EP 342
DI 10.1002/mds.24965
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA 906IS
UT WOS:000301339300003
PM 22411845
ER

PT J
AU McDonald, LM
   Page, D
   Wilkinson, L
   Jahanshahi, M
AF McDonald, Louise M.
   Page, Donna
   Wilkinson, Leonora
   Jahanshahi, Marjan
TI Deep brain stimulation of the subthalamic nucleus improves sense of
   well-being in parkinson's disease
SO MOVEMENT DISORDERS
LA English
DT Article
DE Parkinson's disease; deep brain stimulation; subthalamic nucleus; mood;
   emotion
ID NONMOTOR FLUCTUATIONS; DOPAMINE; LEVODOPA; APATHY; MOOD; SURGERY;
   REWARD; SCALE
AB Deep brain stimulation of the subthalamic nucleus is an effective treatment for the motor symptoms of Parkinson's disease. Although a range of psychiatric and behavioral problems have been documented following deep brain stimulation, the short-term effects of subthalamic nucleus stimulation on patients' mood have only been investigated in a few studies. Our aim was to compare self-reported mood in Parkinson's patients with deep brain stimulation of the subthalamic nucleus ON versus OFF. Twenty-three Parkinson's patients with bilateral deep brain stimulation of the subthalamic nucleus and 11 unoperated Parkinson's patients completed a mood visual analogue scale twice. Operated patients were tested with deep brain stimulation of the subthalamic nucleus both ON and OFF. All were assessed on medication. The operated Parkinson's group reported feeling significantly better coordinated, stronger, and more contented with deep brain stimulation ON compared to OFF. Fourteen of the 16 mood scales changed in a positive direction when deep brain stimulation of the subthalamic nucleus was ON. When changes in motor scores were taken into account, the operated patients still reported feeling better-coordinated, but also less gregarious with stimulation ON. Unoperated Parkinson's patients showed no differences on any of these measures between their 2 ratings. Short-term changes in deep brain stimulation of the subthalamic nucleus have a small and mostly positive effect on mood, which may be partly related to improvements in motor symptoms. The implications for day-to-day management of patients with deep brain stimulation of the subthalamic nucleus are discussed. (c) 2012 Movement Disorder Society
C1 [McDonald, Louise M.; Page, Donna; Wilkinson, Leonora; Jahanshahi, Marjan] UCL Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, London, England.
   [Wilkinson, Leonora] NINDS, Behav Neurol Unit, Bethesda, MD 20892 USA.
RP McDonald, LM (reprint author), Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders B, 33 Queen Sq, London WC1N 3BG, England.
EM m.jahanshahi@ucl.ac.uk
FU Parkinson's UK; NIH [NS40862-02]
FX This work was supported by a postdoctoral fellowship from Parkinson's UK
   (to LW) and an NIH R01 grant (NS40862-02 to MJ).
NR 30
TC 6
Z9 8
U1 1
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-3185
EI 1531-8257
J9 MOVEMENT DISORD
JI Mov. Disord.
PD MAR
PY 2012
VL 27
IS 3
BP 372
EP 378
DI 10.1002/mds.24035
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 906IS
UT WOS:000301339300009
PM 22411848
ER

PT J
AU Sfanos, K
   Aloia, A
   De Marzo, A
   Rein, A
AF Sfanos, Karen
   Aloia, Amanda
   De Marzo, Angelo
   Rein, Alan
TI AUTHOR REPLY Learning from a controversy
SO NATURE REVIEWS UROLOGY
LA English
DT Letter
C1 [Sfanos, Karen] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21231 USA.
   [Aloia, Amanda; Rein, Alan] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.
   [De Marzo, Angelo] Johns Hopkins Univ, Sch Med, Brady Urol Res Inst, Baltimore, MD 21231 USA.
   [De Marzo, Angelo] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA.
RP Sfanos, K (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21231 USA.
EM ksfanos@jhmi.edu
OI De Marzo, Angelo/0000-0003-4847-5307
NR 3
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4812
J9 NAT REV UROL
JI Nat. Rev. Urol.
PD MAR
PY 2012
VL 9
IS 3
DI 10.1038/nrurol.2011.225-c2
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 906ZP
UT WOS:000301387900010
ER

PT J
AU Haan, M
   Espeland, MA
   Klein, BE
   Casanova, R
   Gaussoin, SA
   Jackson, RD
   Millen, AE
   Resnick, SM
   Rossouw, JE
   Shumaker, SA
   Wallace, R
   Yaffe, K
AF Haan, M.
   Espeland, M. A.
   Klein, B. E.
   Casanova, R.
   Gaussoin, S. A.
   Jackson, R. D.
   Millen, A. E.
   Resnick, S. M.
   Rossouw, J. E.
   Shumaker, S. A.
   Wallace, R.
   Yaffe, K.
CA Women's Hlth Initiative Memory Stu
   Women's Hlth Initiative Sight Exam
TI Cognitive function and retinal and ischemic brain changes The Women's
   Health Initiative
SO NEUROLOGY
LA English
DT Article
ID POSTMENOPAUSAL HORMONE-THERAPY; WHITE-MATTER LESIONS; SMALL-VESSEL
   DISEASE; MAGNETIC-RESONANCE; MICROVASCULAR ABNORMALITIES;
   ATHEROSCLEROSIS RISK; MACULAR DEGENERATION; ALZHEIMERS-DISEASE; CEREBRAL
   ATROPHY; FASTING GLUCOSE
AB Objective: To examine the association between retinopathy and cognitive decline or brain lesions and volumes in older women.
   Methods: This study included 511 women aged 65 and older who were simultaneously enrolled in the Women's Health Initiative Memory Study and the Sight Examination Study. In this analysis, we examined the link between retinopathy, assessed using fundus photography (2000- 2002), cognitive performance over time assessed by the modified Mini-Mental State Examination (3MSE) (1996-2007), and white matter hyperintensities and lacunar infarcts in the basal ganglia.
   Results: Presence of retinopathy was associated with poorer 3MSE scores (mean difference = 1.01, SE: 0.43) (p = 0.019) over a 10-year follow-up period and greater ischemic volumes in the total brain (47% larger, p = 0.04) and the parietal lobe (68% larger, p = 0.01) but not with measures of regional brain atrophy.
   Conclusions: The correspondence we found between retinopathy and cognitive impairment, along with larger ischemic lesion volumes, strengthens existing evidence that retinopathy as a marker of small vessel disease is a risk factor for cerebrovascular disease that may influence cognitive performance and related brain changes. Retinopathy may be useful as a clinical tool if it can be shown to be an early marker related to neurologic outcomes. Neurology (R) 2012;78:942-949
C1 [Haan, M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
   [Yaffe, K.] Univ Calif San Francisco, Dept Psychiat & Neurol, San Francisco, CA 94143 USA.
   [Espeland, M. A.; Casanova, R.; Gaussoin, S. A.; Yaffe, K.] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
   [Shumaker, S. A.] Wake Forest Univ, Bowman Gray Sch Med, Dept Social Sci & Hlth Policy, Winston Salem, NC USA.
   [Jackson, R. D.] Ohio State Univ, Med Ctr, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA.
   [Millen, A. E.] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
   [Klein, B. E.] Univ Wisconsin, Dept Ophthalmol, Madison, WI 53706 USA.
   [Resnick, S. M.] NIA, Lab Personal & Cognit, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
   [Rossouw, J. E.] NHLBI, Womens Hlth Initiat Branch, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
   [Wallace, R.] Univ Iowa, Coll Med, Dept Epidemiol, Iowa City, IA USA.
RP Haan, M (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
EM Mary.Haan@ucsf.edu
FU National Heart, Lung, and Blood Institute of the National Institutes of
   Health; US Department of Health and Human Services; Wyeth
   Pharmaceuticals, Inc; Intramural Research Program, NIA, NIH
FX The Women's Health Initiative is funded by the National Heart, Lung, and
   Blood Institute of the National Institutes of Health, US Department of
   Health and Human Services. The Women's Health Initiative Sight Exam and
   the Memory Study were funded in part by Wyeth Pharmaceuticals, Inc, St.
   Davids, PA. SMR is supported by the Intramural Research Program, NIA,
   NIH.
NR 38
TC 22
Z9 22
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD MAR
PY 2012
VL 78
IS 13
BP 942
EP 949
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 916TH
UT WOS:000302125600007
PM 22422889
ER

PT J
AU Silberstein, SD
   Dodick, DW
   Lindblad, AS
   Holroyd, K
   Harrington, M
   Mathew, NT
   Hirtz, D
AF Silberstein, S. D.
   Dodick, D. W.
   Lindblad, A. S.
   Holroyd, K.
   Harrington, M.
   Mathew, N. T.
   Hirtz, D.
TI Randomized, placebo-controlled trial of propranolol added to topiramate
   in chronic migraine
SO NEUROLOGY
LA English
DT Article
ID CHRONIC DAILY HEADACHE; DOUBLE-BLIND; CONTROLLED PHASE; CLINICAL-TRIALS;
   ONABOTULINUMTOXINA; PREVALENCE; GUIDELINES; EFFICACY; THERAPY
AB Objective: To assess the efficacy and safety of adding propranolol to topiramate in chronic migraine subjects inadequately controlled with topiramate alone.
   Methods: This was a double-blind, placebo-controlled, randomized clinical trial conducted through the National Institute of Neurological Disorders and Stroke Clinical Research Collaboration, expected to randomize 250 chronic migraine subjects inadequately controlled (>= 10 headaches/month) with topiramate (50-100 mg/day) to either propranolol LA (long acting) (240 mg/day) or placebo. Primary outcome was 28-day moderate to severe headache rate reduction at 6 months (weeks 16 to 24) compared with baseline (weeks -4 to 0).
   Results: A planned interim analysis was performed after 48 sites randomized 171 subjects. The data and safety monitoring board recommended ending the trial after determining that it would be highly unlikely for the combination to result in a significant reduction in 28-day headache rate compared with topiramate alone if all 250 subjects were randomized. No safety concerns were identified. At study closure, 191 subjects were randomized. The 6-month reduction in moderate to severe 28-day headache rate and total 28-day headache rate for combination therapy vs topiramate alone was not significantly different: 4.0 vs 4.5 days (moderate to severe 28-day headache rate; p = 0.57) and 6.2 vs 6.1 days (total 28-day headache rate; p = 0.91).
   Conclusions: This study does not provide evidence that the addition of propranolol LA to topiramate adds benefit when chronic migraine is inadequately controlled with topiramate alone.
   Classification of evidence: This study provides Class II evidence that propranolol LA, added to topiramate, is ineffective in chronic migraine patients who fail topiramate monotherapy. Neurology (R) 2012;78:976-984
C1 [Lindblad, A. S.; Harrington, M.] EMMES Corp EMMES, Rockville, MD USA.
   [Silberstein, S. D.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
   [Dodick, D. W.] Mayo Clin, Phoenix, AZ USA.
   [Holroyd, K.] Ohio Univ, Athens, OH 45701 USA.
   [Mathew, N. T.] Houston Headache Clin, Houston, TX USA.
   [Hirtz, D.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA.
RP Lindblad, AS (reprint author), EMMES Corp EMMES, Rockville, MD USA.
EM alindblad@emmes.com
FU NIH National Institute of Neurological Disorders and Stroke
   [HHSN265200523641C]; AGA; Allergan; Boston Scientific; CAPNIA; Coherex;
   Endo; GlaxoSmithKline; Lilly; MAP; Medtronic; Merck; NIH/NINDS; NuPathe;
   St. Jude Medical; Valeant; Zogenix, Inc.; American Headache Society;
   International Headache Society; CogniMed Inc.; Miller Medical; Annenberg
   Center for Health Sciences; Medtronic, Inc.; Advanced Neurostimulation
   Systems; St. Jude Medical, Inc.; Endo Pharmaceuticals; NIH; Merck
   Serono; AstraZeneca; Pfizer Inc
FX Supported by NIH National Institute of Neurological Disorders and Stroke
   Contract HHSN265200523641C. Ortho-McNeil-Janssen Pharmaceuticals, Inc.,
   donated the study-supplied topiramate used during the screening and
   randomization phases of this study.; Dr. Silberstein serves on
   scientific advisory boards for AGA Medical Corporation, Allergan, Inc.,
   Amgen, Boston Scientific, CAPNIA, Coherex Medical, CoLucid
   Pharmaceuticals, CyDex Pharmaceuticals, Inc., GlaxoSmithKline, Eli Lilly
   and Company, MAP Pharmaceuticals, Inc., Medtronic, Inc., Merck Serono,
   Minster Pharmaceuticals plc, Neuralieve Inc., the NIH/NINDS, NuPathe
   Inc., Pfizer Inc, St. Jude Medical, and Valeant Pharmaceuticals
   International; serves on the editorial boards of Cephalalgia and Current
   Pain and Headache Reports; serves on the speakers' bureaus for Endo
   Pharmaceuticals, GlaxoSmithKline, and Merck Serono; serves as a
   consultant for Amgen, Novartis, Opti-Nose, and Sepracor Inc.; receives
   publishing royalties for Wolff's Headache, 8th edition (Oxford
   University Press, 2009) and Handbook of Headache (Cambridge University
   Press, 2010); his employer receives research support from AGA, Allergan,
   Boston Scientific, CAPNIA, Coherex, Endo, GlaxoSmithKline, Lilly, MAP,
   Medtronic, Merck, the NIH/NINDS, NuPathe, St. Jude Medical, Valeant, and
   Zogenix, Inc.; and receives research support from the American Headache
   Society and the International Headache Society. Dr. Dodick serves on
   scientific advisory boards and as a consultant for Allergan, Inc.,
   Pfizer Inc., Novartis, Merck Serono, NuPath Inc., Nautilus, Coherex
   Medical, Boston Scientific, Medtronic, Inc., GlaxoSmithKline, CoLucid
   Pharmaceuticals, Autonomic Technologies, Eli Lilly and Company, Miller
   Medical, Neuralieve Inc., NeurAxon, Inc., St. Jude Medical, Inc.,
   Zogenix, Inc., CogniMed Inc., MAP Pharmaceuticals, Inc., Lundbeck Inc.,
   IMPAX Laboratories, Inc., and the NIH/NINDS; has received funding for
   travel or speaker honoraria from CogniMed Inc., Miller Medical, and
   Annenberg Center for Health Sciences; serves as Editor-in-Chief of
   Cephalalgia, Editor-in-Chief and on the editorial boards of The
   Neurologist, Lancet Neurology, and Postgraduate Medicine; and has served
   as Editor-in-Chief of Headache Currents and as an Associate Editor of
   Headache; receives publishing royalties for Wolff's Headache, 8th
   edition (Oxford University Press, 2009) and Handbook of Headache
   (Cambridge University Press, 2010); and receives research support from
   Boston Scientific, Medtronic, Inc., Advanced Neurostimulation Systems,
   St. Jude Medical, Inc., and the NIH/NINDS. Dr. Lindblad receives salary
   from and is part owner of The EMMES Corporation, a Coordinating Center
   for clinical trials. Dr. Holroyd has served as a consultant for Endo
   Pharmaceuticals and Takeda Pharmaceutical Company Limited and received
   research support from Endo Pharmaceuticals and the NIH. M. Harrington
   receives salary from The EMMES Corporation, a Coordinating Center for
   clinical trials. Dr. Mathew has served on scientific advisory boards for
   Allergan, Inc., GlaxoSmithKline, and Nautilus; has served on speakers'
   bureaus for and received speaker honoraria from GlaxoSmithKline,
   Nautilus, Allergan, Inc.; and has received research support from Merck
   Serono, AstraZeneca, Pfizer Inc, and Endo Pharmaceuticals. Dr. Hirtz
   reports no disclosures.
NR 20
TC 23
Z9 23
U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD MAR
PY 2012
VL 78
IS 13
BP 976
EP 984
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA 916TH
UT WOS:000302125600012
PM 22377815
ER

PT J
AU Ranzenhofer, LM
   Columbo, KM
   Tanofsky-Kraff, M
   Shomaker, LB
   Cassidy, O
   Matheson, BE
   Kolotkin, RL
   Checchi, JM
   Keil, M
   McDuffie, JR
   Yanovski, JA
AF Ranzenhofer, Lisa M.
   Columbo, Kelli M.
   Tanofsky-Kraff, Marian
   Shomaker, Lauren B.
   Cassidy, Omni
   Matheson, Brittany E.
   Kolotkin, Ronette L.
   Checchi, Jenna M.
   Keil, Margaret
   McDuffie, Jennifer R.
   Yanovski, Jack A.
TI Binge Eating and Weight-Related Quality of Life in Obese Adolescents
SO NUTRIENTS
LA English
DT Article
DE weight-related quality of life (WR-QOL); binge eating; adolescent;
   obesity
ID AFRICAN-AMERICAN; HEALTH; OVERWEIGHT; CHILDREN; BEHAVIORS; DISORDER;
   IMPACT; PSYCHOPATHOLOGY; POPULATION; PREVALENCE
AB Limited data exist regarding the association between binge eating and quality of life (QOL) in obese adolescent girls and boys. We, therefore, studied binge eating and QOL in 158 obese (BMI = 95th percentile) adolescents (14.5 +/- 1.4 years, 68.0% female, 59% African-American) prior to weight-loss treatment. Youth completed an interview to assess binge eating and a questionnaire measure of QOL. Controlling for body composition, binge eating youth (n = 35), overall, reported poorer QOL in domains of health, mobility, and self-esteem compared to those without binge eating (ps < 0.05). Also, girls, overall, reported poorer QOL than boys in activities of daily-living, mobility, self-esteem, and social/interpersonal functioning (ps < 0.05). Girls with binge eating reported the greatest impairments in activities of daily living, mobility, self-esteem, social/interpersonal functioning, and work/school QOL (ps < 0.05). Among treatment-seeking obese adolescents, binge eating appears to be a marker of QOL impairment, especially among girls. Prospective and treatment designs are needed to explore the directional relationship between binge eating and QOL and their impact on weight outcomes.
C1 [Ranzenhofer, Lisa M.; Columbo, Kelli M.; Tanofsky-Kraff, Marian; Shomaker, Lauren B.; Cassidy, Omni; Matheson, Brittany E.; Checchi, Jenna M.; Keil, Margaret; Yanovski, Jack A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
   [Ranzenhofer, Lisa M.; Columbo, Kelli M.; Tanofsky-Kraff, Marian; Shomaker, Lauren B.; Cassidy, Omni; Matheson, Brittany E.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
   [Kolotkin, Ronette L.; McDuffie, Jennifer R.] Duke Univ Hlth Syst, Dept Community & Family Med, Durham, NC 27710 USA.
   [Kolotkin, Ronette L.] Obes & Qual Life Consulting, Durham, NC 27705 USA.
RP Tanofsky-Kraff, M (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
EM Lisa.Ranzenhofer@usuhs.mil; k_columbo@yahoo.com; mtanofsky@usuhs.mil;
   shomakel@mail.nih.gov; omni.cassidy@nih.gov; brittany.matheson@nih.gov;
   rkolotkin@qualityoflifeconsulting.com; jenchec@gmail.com;
   keilm@mail.nih.gov; mcduf.j@duke.edu; yanovskj@mail.nih.gov
OI Yanovski, Jack/0000-0001-8542-1637
FU NICHD, NIH [1ZIAHD000641]; NIMHD
FX Research support: Intramural Research Program, NICHD, NIH, grant
   1ZIAHD000641 with supplemental funding from NIMHD (to J. Yanovski).
NR 46
TC 13
Z9 15
U1 0
U2 10
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 2072-6643
J9 NUTRIENTS
JI Nutrients
PD MAR
PY 2012
VL 4
IS 3
BP 167
EP 180
DI 10.3390/nu4030167
PG 14
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 916RP
UT WOS:000302121200002
PM 22666544
ER

PT J
AU Liu, XF
   Xiang, L
   Zhang, Y
   Becker, KG
   Bera, TK
   Pastan, I
AF Liu, X-F
   Xiang, L.
   Zhang, Y.
   Becker, K. G.
   Bera, T. K.
   Pastan, I.
TI CAPC negatively regulates NF-kappa B activation and suppresses tumor
   growth and metastasis
SO ONCOGENE
LA English
DT Article
DE CAPC; tumor growth; NF-kappa B; cytokines
ID BREAST-CANCER CELLS; COLORECTAL-CANCER; CYSTATIN SN; INFLAMMATION;
   PROTEIN; PATHWAY; GENES
AB CAPC, also known as LRRC26, is expressed in normal prostate and salivary gland. We developed a mAb to CAPC and used it to characterize the protein and study its function. CAPC protein was detected in normal prostate and salivary gland, in several human breast cancer cell lines and in the prostate cancer cell line LNCaP. Knockdown of CAPC by siRNA in LNCaP cells enhanced anchorage-independent growth in soft agar. Conversely, overexpression of CAPC in MDA-231 breast cancer cells and A431 epidermoid cancer cells inhibited growth in soft agar and tumorigenesis in nude mice, and suppressed the metastasis of MDA-231 cells to the lung. Overexpression of CAPC downregulated NF-kappa B activity and its target genes, including GM-CSF (CSF2), CXCL1, IL8 and LTB1. It also suppressed genes encoding the serine protease mesotrypsin (PRSS3) and cystatin SN (CST1). CAPC expressing tumors showed a decrease in the number of proliferating cells and a large increase in ECM. The role of CAPC in the suppression of tumor growth and metastasis may be through its alteration of the tumor microenvironment. Oncogene (2012) 31, 1673-1682; doi:10.1038/onc.2011.355; published online 8 August 2011
C1 [Liu, X-F; Xiang, L.; Bera, T. K.; Pastan, I.] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Zhang, Y.; Becker, K. G.] NIA, Gene Express & Genom Unit, Res Resources Branch, NIH, Baltimore, MD 21224 USA.
RP Pastan, I (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 5106, Bethesda, MD 20892 USA.
EM pastani@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research; National
   Institute on Aging
FX The CAPC antibody was provided by BD BioSciences Pharmingen as an
   outcome of Antibody Co-development Collaboration between the NCI and BD
   BioSciences. We thank William H Wood III (National Institute on Aging)
   and the Confocal Core Facility members (Center for Cancer Research, NIH)
   for technical assistance. 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 the National Institute on
   Aging.
NR 27
TC 9
Z9 9
U1 1
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD MAR
PY 2012
VL 31
IS 13
BP 1673
EP 1682
DI 10.1038/onc.2011.355
PG 10
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
GA 918EF
UT WOS:000302231400006
PM 21822313
ER

PT J
AU Spong, CY
AF Spong, Catherine Y.
TI To VBAC or Not to VBAC
SO PLOS MEDICINE
LA English
DT Editorial Material
C1 NICHHD, Bethesda, MD 20892 USA.
RP Spong, CY (reprint author), NICHHD, Bethesda, MD 20892 USA.
EM spongc@mail.nih.gov
NR 8
TC 3
Z9 3
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1549-1277
J9 PLOS MED
JI PLos Med.
PD MAR
PY 2012
VL 9
IS 3
AR e1001191
DI 10.1371/journal.pmed.1001191
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 916VY
UT WOS:000302132500011
PM 22427748
ER

PT J
AU Nguyen, TB
   Wang, SJ
   Anugu, V
   Rose, N
   McKenna, M
   Petrick, N
   Burns, JE
   Summers, RM
AF Nguyen, Tan B.
   Wang, Shijun
   Anugu, Vishal
   Rose, Natalie
   McKenna, Matthew
   Petrick, Nicholas
   Burns, Joseph E.
   Summers, Ronald M.
TI Distributed Human Intelligence for Colonic Polyp Classification in
   Computer-aided Detection for CT Colonography
SO RADIOLOGY
LA English
DT Article
ID TOMOGRAPHIC VIRTUAL COLONOSCOPY; OBSERVER PERFORMANCE; FEASIBILITY;
   POPULATION; CURVES; READER
AB Purpose: To assess the diagnostic performance of distributed human intelligence for the classification of polyp candidates identified with computer-aided detection (CAD) for computed tomographic (CT) colonography.
   Materials and Methods: This study was approved by the institutional Office of Human Subjects Research. The requirement for informed consent was waived for this HIPAA-compliant study. CT images from 24 patients, each with at least one polyp of 6 mm or larger, were analyzed by using CAD software to identify 268 polyp candidates. Twenty knowledge workers (KWs) from a crowdsourcing platform labeled each polyp candidate as a true or false polyp. Two trials involving 228 KWs were conducted to assess reproducibility. Performance was assessed by comparing the area under the receiver operating characteristic curve (AUC) of KWs with the AUC of CAD for polyp classification.
   Results: The detection-level AUC for KWs was 0.845 +/- 0.045 (standard error) in trial 1 and 0.855 +/- 0.044 in trial 2. These were not significantly different from the AUC for CAD, which was 0.859 +/- 0.043. When polyp candidates were stratified by difficulty, KWs performed better than CAD on easy detections; AUCs were 0.951 +/- 0.032 in trial 1, 0.966 +/- 0.027 in trial 2, and 0.877 +/- 0.048 for CAD (P = .039 for trial 2). KWs who participated in both trials showed a significant improvement in performance going from trial 1 to trial 2; AUCs were 0.759 +/- 0.052 in trial 1 and 0.839 +/- 0.046 in trial 2 (P = .041).
   Conclusion: The performance of distributed human intelligence is not significantly different from that of CAD for colonic polyp classification.
C1 [Nguyen, Tan B.; Wang, Shijun; Anugu, Vishal; Rose, Natalie; McKenna, Matthew; Burns, Joseph E.; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA.
   [Petrick, Nicholas] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
   [Burns, Joseph E.] Univ Calif Irvine, Irvine Med Ctr, Dept Radiol Sci, Orange, CA 92668 USA.
RP Summers, RM (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, 10 Ctr Dr,Bldg 10,Room 1C224D,MSC 1182, Bethesda, MD 20892 USA.
EM rms@nih.gov
FU National Institutes of Health, Clinical Center; Clinical Research
   Training Program; National Institutes of Health; Pfizer; iCAD Medical;
   iCAD
FX J.E.B., and R.M.S. supported by the Intramural Research Programs of the
   National Institutes of Health, Clinical Center. T.B.N. supported in part
   through the Clinical Research Training Program, a public-private
   partnership supported jointly by the National Institutes of Health and
   Pfizer (via a grant to the Foundation for the National Institutes of
   Health from Pfizer).; T.B.N. Financial activities related to the present
   article: received grant through the Clinical Research Training Program,
   a public-private partnership supported jointly by the National
   Institutes of Health and Pfizer (via a grant to the Foundation for the
   National Institutes of Health from Pfizer). Financial activities not
   related to the present article: none to disclose. Other relationships:
   none to disclose. S. W. No potential conflicts of interest to disclose.
   V. A. No potential conflicts of interest to disclose. N.R. No potential
   conflicts of interest to disclose. M. M. No potential conflicts of
   interest to disclose. N.P. Financial activities related to the present
   article: none to disclose. Financial activities not related to the
   present article: author and institution have patent applications
   submitted in related areas for the National Institutes of Health and the
   Food and Drug Administration. Other relationships: none to disclose.
   J.E.B. No potential conflicts of interest to disclose. R. M. S.
   Financial activities related to the present article: none to disclose.
   Financial activities not related to the present article: received grant
   from iCAD Medical; author and institution receive royalties for a patent
   license from iCAD Medical and software license from Translational
   Sciences Corporation and have patents issued and pending in related
   areas. Other relationships: Viatronix provided the V3D-Colon software
   free of charge to author's laboratory, and software was used in the
   submitted work; author's laboratory is supported in part by a
   Cooperative Research and Development Agreement with iCAD; is a
   stockholder of Johnson & Johnson.
NR 31
TC 25
Z9 26
U1 2
U2 9
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD MAR
PY 2012
VL 262
IS 3
BP 824
EP 833
DI 10.1148/radiol.11110938
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 916RR
UT WOS:000302121400011
PM 22274839
ER

PT J
AU Balzer, EM
   Konstantopoulos, K
AF Balzer, Eric M.
   Konstantopoulos, Konstantinos
TI Intercellular adhesion: mechanisms for growth and metastasis of
   epithelial cancers
SO WILEY INTERDISCIPLINARY REVIEWS-SYSTEMS BIOLOGY AND MEDICINE
LA English
DT Article
ID CELL-CELL-ADHESION; TO-MESENCHYMAL TRANSITION; COLON-CARCINOMA CELLS;
   E-CADHERIN EXPRESSION; INDUCED PLATELET-AGGREGATION; TRANSCRIPTION
   FACTOR SNAIL; NATURAL-KILLER-CELLS; BREAST-TUMOR CELLS; N-CADHERIN;
   BETA-CATENIN
AB Cellcell adhesion molecules (CAMs) comprise a broad class of linker proteins that are crucial for the development of multicellular organisms, and for the continued maintenance of organ and tissue structure. Because of its pivotal function in tissue homeostasis, the deregulation of intercellular adhesion is linked to the onset of most solid tumors. The breakdown of homeostatic cell adhesions in highly ordered epithelial sheets is directly implicated in carcinogenesis, while continued changes in the adhesion profile of the primary tumor mass facilitate growth and expansion into adjacent tissue. Intercellular adhesion molecules are also involved in each subsequent phase of metastasis, including transendothelial migration, transit through the bloodstream or lymphatics, and renewed proliferation in secondary sites. This review addresses various roles of cadherin- and selectin-mediated intercellular adhesion in tumor initiation and malignant transformation, and discusses the mechanisms for the arrest and adhesion of circulating tumor cells to the vessel endothelium. Considering the contributions of these CAMs to cancer progression in the context of a systematic biological framework may prove valuable in identifying new ways to diagnose and treat cancer. WIREs Syst Biol Med 2012, 4:171181. doi: 10.1002/wsbm.160
C1 [Balzer, Eric M.; Konstantopoulos, Konstantinos] Johns Hopkins Univ, Inst NanoBioTechnol, Baltimore, MD 21218 USA.
   [Balzer, Eric M.; Konstantopoulos, Konstantinos] Johns Hopkins Univ, Johns Hopkins Engn Oncol Ctr, Phys Sci Oncol Ctr, NCI, Baltimore, MD USA.
   [Balzer, Eric M.; Konstantopoulos, Konstantinos] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD USA.
RP Konstantopoulos, K (reprint author), Johns Hopkins Univ, Inst NanoBioTechnol, Baltimore, MD 21218 USA.
EM kkonsta1@jhu.edu
RI Konstantopoulos, Konstantinos/A-7045-2011
FU NIH/NCI [T32CA130840, R01 CA101135, U54 CA143868]
FX This work was supported by NIH/NCI T32CA130840, R01 CA101135 and U54
   CA143868.
NR 92
TC 14
Z9 14
U1 0
U2 14
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1939-5094
J9 WIRES SYST BIOL MED
JI Wiley Interdiscip. Rev.-Syst. Biol
PD MAR-APR
PY 2012
VL 4
IS 2
BP 171
EP 181
DI 10.1002/wsbm.160
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 896LZ
UT WOS:000300569300004
PM 21913338
ER

PT J
AU Selker, HP
   Beshansky, JR
   Griffith, JL
   D'Agostino, RB
   Massaro, JM
   Udelson, JE
   Rashba, EJ
   Ruthazer, R
   Sheehan, PR
   Desvigne-Nickens, P
   Rosenberg, YD
   Atkins, JM
   Sayah, AJ
   Aufderheide, TP
   Rackley, CE
   Opie, LH
   Lambrew, CT
   Cobb, LA
   MacLeod, BA
   Ingwall, JS
   Zalenski, RJ
   Apstein, CS
AF Selker, Harry P.
   Beshansky, Joni R.
   Griffith, John L.
   D'Agostino, Ralph B.
   Massaro, Joseph M.
   Udelson, James E.
   Rashba, Eric J.
   Ruthazer, Robin
   Sheehan, Patricia R.
   Desvigne-Nickens, Patrice
   Rosenberg, Yves D.
   Atkins, James M.
   Sayah, Assaad J.
   Aufderheide, Tom P.
   Rackley, Charles E.
   Opie, Lionel H.
   Lambrew, Costas T.
   Cobb, Leonard A.
   MacLeod, Bruce A.
   Ingwall, Joanne S.
   Zalenski, Robert J.
   Apstein, Carl S.
TI Study design for the Immediate Myocardial Metabolic Enhancement During
   Initial Assessment and Treatment in Emergency Care (IMMEDIATE) Trial: A
   double-blind randomized controlled trial of intravenous glucose,
   insulin, and potassium for acute coronary syndromes in emergency medical
   services
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID ACUTE CARDIAC ISCHEMIA; LONG-TERM SURVIVAL; PREDICTIVE INSTRUMENT;
   FATTY-ACIDS; INFARCTION; INFUSION; THERAPY; MULTICENTER; ARRHYTHMIAS;
   MORTALITY
AB Background Experimental studies suggest that metabolic myocardial support by intravenous (IV) glucose, insulin, and potassium (GIK) reduces ischemia-induced arrhythmias, cardiac arrest, mortality, progression from unstable angina pectoris to acute myocardial infarction (AMI), and myocardial infarction size. However, trials of hospital administration of IV GIK to patients with ST-elevation myocardial infarction (STEMI) have generally not shown favorable effects possibly because of the GIK intervention taking place many hours after ischemic symptom onset. A trial of GIK used in the very first hours of ischemia has been needed, consistent with the timing of benefit seen in experimental studies.
   Objective The IMMEDIATE Trial tested whether, if given very early, GIK could have the impact seen in experimental studies. Accordingly, distinct from prior trials, IMMEDIATE tested the impact of GIK (1) in patients with acute coronary syndromes (ACS), rather than only AMI or STEMI, and (2) administered in prehospital emergency medical service settings, rather than later, in hospitals, after emergency department evaluation.
   Design The IMMEDIATE Trial was an emergency medical service-based randomized placebo-controlled clinical effectiveness trial conducted in 13 cities across the United States that enrolled 911 participants. Eligible were patients 30 years or older for whom a paramedic performed a 12-lead electrocardiogram to evaluate chest pain or other symptoms suggestive of ACS for whom electrocardiograph-based acute cardiac ischemia time-insensitive predictive instrument indicated a >= 75% probability of ACS, and/or the thrombolytic predictive instrument indicated the presence of a STEMI, or if local criteria for STEMI notification of receiving hospitals were met. Prehospital IV GIK or placebo was started immediately. Prespecified were the primary end point of progression of ACS to infarction and, as major secondary end points, the composite of cardiac arrest or in-hospital mortality, 30-day mortality, and the composite of cardiac arrest, 30-day mortality, or hospitalization for heart failure. Analyses were planned on an intent-to-treat basis, on a modified intent-to-treat group who were confirmed in emergency departments to have ACS, and for participants presenting with STEMI.
   Conclusion The IMMEDIATE Trial tested whether GIK, when administered as early as possible in the course of ACS by paramedics using acute cardiac ischemia time-insensitive predictive instrument and thrombolytic predictive instrument decision support, would reduce progression to AMI, mortality, cardiac arrest, and heart failure. It also tested whether it would provide clinical and pathophysiologic information on GIK's biological mechanisms. (Am Heart J 2012;163:315-22.)
C1 [Selker, Harry P.; Beshansky, Joni R.; Griffith, John L.; Ruthazer, Robin; Sheehan, Patricia R.] Tufts Univ, Sch Med, Ctr Cardiovasc Hlth Serv Res, Inst Clin Res & Hlth Policy Studies,Tufts Med Ctr, Boston, MA 02111 USA.
   [D'Agostino, Ralph B.] Boston Univ, Dept Math, Boston, MA 02215 USA.
   [Massaro, Joseph M.] Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA.
   [Udelson, James E.] Tufts Med Ctr, Div Cardiol, Boston, MA USA.
   [Udelson, James E.] Tufts Med Ctr, CardioVasc Ctr, Boston, MA USA.
   [Rashba, Eric J.] SUNY Stony Brook, Med Ctr, Div Cardiol, Sect Electrophysiol, Stony Brook, NY 11794 USA.
   [Desvigne-Nickens, Patrice; Rosenberg, Yves D.] NHLBI, Rockville, MD USA.
   [Atkins, James M.] Univ Texas SW Med Sch, Dept Med, Dallas, TX USA.
   [Sayah, Assaad J.] Cambridge Hlth Alliance, Dept Emergency Med, Cambridge, MA USA.
   [Aufderheide, Tom P.] Med Coll Wisconsin, Dept Emergency Med, Milwaukee, WI 53226 USA.
   [Rackley, Charles E.] Georgetown Med Ctr, Lipid Disorders Ctr, Washington, DC USA.
   [Opie, Lionel H.] Univ Cape Town, Dept Med, Hatter Cardiovasc Res Inst Africa, ZA-7925 Cape Town, South Africa.
   [Lambrew, Costas T.] Maine Med Ctr, Div Cardiol, Portland, ME 04102 USA.
   [Cobb, Leonard A.] Univ Washington, Med Ctr, Dept Med, Seattle, WA 98195 USA.
   [MacLeod, Bruce A.] UPMC Mercy Hosp, Dept Emergency Med, Pittsburgh, PA USA.
   [Ingwall, Joanne S.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
   [Zalenski, Robert J.] Wayne State Univ, Dept Emergency Med, Detroit, MI USA.
RP Selker, HP (reprint author), Tufts Univ, Sch Med, Ctr Cardiovasc Hlth Serv Res, Inst Clin Res & Hlth Policy Studies,Tufts Med Ctr, 800 Washington St 63, Boston, MA 02111 USA.
EM hselker@tuftsmedicalcenter.org
FU National Heart, Lung, and Blood Institute [U01HL07782, U01HL077826,
   U01HL077823, U01HL77822]
FX Funding support for the IMMEDIATE Trial was provided by the National
   Heart, Lung, and Blood Institute (grants: U01HL07782, U01HL077826,
   U01HL077823, U01HL77822).
NR 19
TC 12
Z9 13
U1 0
U2 8
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
J9 AM HEART J
JI Am. Heart J.
PD MAR
PY 2012
VL 163
IS 3
BP 315
EP 322
DI 10.1016/j.ahj.2012.02.002
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 909WO
UT WOS:000301597200005
PM 22424000
ER

PT J
AU Hoffmann, U
   Truong, QA
   Fleg, JL
   Goehler, A
   Gazelle, S
   Wiviott, S
   Lee, H
   Udelson, JE
   Schoenfeld, D
AF Hoffmann, Udo
   Truong, Quynh A.
   Fleg, Jerome L.
   Goehler, Alexander
   Gazelle, Scott
   Wiviott, Stephen
   Lee, Hang
   Udelson, James E.
   Schoenfeld, David
TI Design of the Rule Out Myocardial Ischemia/Infarction Using Computer
   Assisted Tomography: A multicenter randomized comparative effectiveness
   trial of cardiac computed tomography versus alternative triage
   strategies in patients with acute chest pain in the emergency department
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID ACUTE CORONARY SYNDROMES; TIMI RISK SCORE; CT ANGIOGRAPHY; ROMICAT
   TRIAL; PERFORMANCE; POPULATION; OUTCOMES
AB Although early cardiac computed tomographic angiography (CCTA) might improve the management of emergency department (ED) patients with acute chest pain, it could also result in increased testing, costs, and radiation exposure. ROMICAT II was a randomized comparative effectiveness trial enrolling patients 40 to 74 years old without known coronary artery disease who presented to the ED with chest pain but without ischemic electrocardiographic (ECG) changes or elevated initial troponin and who required further risk stratification. Overall, 1000 patients at 9 sites within the United States were randomized to either CCTA as the first diagnostic test following serial biomarkers or to standard of care, which included no testing or functional testing such as exercise ECG, stress radionuclide imaging, or stress echocardiography. Test results were provided to ED physicians, yet patient management was not driven by a study protocol in either arm. Data were collected on diagnostic testing, cardiac events, and cost of medical care for the index hospitalization and during the following 28 days. The primary end point was length of hospital stay. Secondary end points were cumulative radiation exposure, resource utilization, and costs of competing strategies. Tertiary end points were institutional, physician, and patient characteristics associated with primary and secondary outcomes. Rate of missed acute coronary syndrome within 28 days was the safety end point. The ROMICAT II will provide rigorous data on whether CCTA is more efficient than standard of care in the management of patients with acute chest pain at intermediate risk for acute coronary syndrome. (Am Heart J 2012;163:330-338.e1.)
C1 [Hoffmann, Udo; Truong, Quynh A.; Goehler, Alexander] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA.
   [Hoffmann, Udo; Truong, Quynh A.; Goehler, Alexander; Gazelle, Scott; Wiviott, Stephen; Lee, Hang; Schoenfeld, David] Harvard Univ, Sch Med, Boston, MA USA.
   [Hoffmann, Udo; Truong, Quynh A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
   [Fleg, Jerome L.] NHLBI, Bethesda, MD 20892 USA.
   [Goehler, Alexander; Gazelle, Scott] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA.
   [Wiviott, Stephen] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
   [Wiviott, Stephen] TIMI Study Grp, Boston, MA USA.
   [Wiviott, Stephen; Lee, Hang; Schoenfeld, David] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA.
   [Udelson, James E.] Tufts Med Ctr, Ctr Cardiovasc, Boston, MA USA.
RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA.
EM uhoffmann@partners.org
RI Shapiro, Nathan/F-1718-2016
FU NHLBI [U01HL092040]; NIH [K23HL098370, L30HL093896]
FX The study is funded by the NHLBI U01HL092040. Dr. Truong received
   support from NIH grants K23HL098370 and L30HL093896.
NR 28
TC 16
Z9 17
U1 0
U2 4
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
J9 AM HEART J
JI Am. Heart J.
PD MAR
PY 2012
VL 163
IS 3
BP 330
EP U269
DI 10.1016/j.ahj.2012.01.028
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 909WO
UT WOS:000301597200007
PM 22424002
ER

PT J
AU Reynolds, HR
   Forman, SA
   Tamis-Holland, JE
   Steg, PG
   Mark, DB
   Pearte, CA
   Carvalho, AC
   Sopko, G
   Liu, L
   Lamas, GA
   Kruk, M
   Loboz-Grudzien, K
   Ruzyllo, W
   Hochman, JS
AF Reynolds, Harmony R.
   Forman, Sandra A.
   Tamis-Holland, Jacqueline E.
   Steg, Philippe Gabriel
   Mark, Daniel B.
   Pearte, Camille A.
   Carvalho, Antonio C.
   Sopko, George
   Liu, Li
   Lamas, Gervasio A.
   Kruk, Mariusz
   Loboz-Grudzien, Krystyna
   Ruzyllo, Witold
   Hochman, Judith S.
TI Relationship of female sex to outcomes after myocardial infarction with
   persistent total occlusion of the infarct artery: Analysis of the
   Occluded Artery Trial (OAT)
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID PERCUTANEOUS CORONARY INTERVENTION; GENDER-DIFFERENCES; REPERFUSION
   THERAPY; MORTALITY; PREDICTORS; REGISTRY; IMPACT; WOMEN; MEN
AB Background Long-term follow-up (up to 9 years) from the OAT allows for the examination of sex differences in outcomes and the effect of percutaneous coronary intervention (PCI) in a relatively homogeneous cohort of myocardial infarction (MI) survivors.
   Methods The OAT randomized 484 (22%) women and 1717 men to PCI of the occluded infarct-related artery vs medical therapy alone >24 hours post-MI. There was no benefit of PCI on the composite of death, MI, and class IV heart failure. We analyzed outcomes by sex and investigated for sex-based trial selection bias using a concurrent registry.
   Results Women were older and more likely to have left anterior descending infarct-related artery, diabetes and hypertension, history of heart failure, and rales at randomization but were less likely to smoke. The proportion and characteristics of women enrolled in the trial and the registry were similar, including left ventricular ejection fraction and extent of disease. Women had higher rates of the primary composite (hazard ratio [HR] 1.48, P = .0002), death (HR 1.50, P = .001), and heart failure (HR 2.53, P < .0001) but not reinfarction (HR 1.12, P = .57). Female sex was not independently associated with the primary end point or death on multivariate analysis. There was a trend toward independent association of female sex with heart failure (HR 1.66, P = .02).
   Conclusion Women in OAT had a higher primary end point event rate than did men, mainly driven by heart failure. Female sex was not independently associated with death or MI in this well-defined cohort with comparable extent of coronary artery disease, similar medical therapy, and equivalent left ventricular ejection fraction by sex. (Am Heart J 2012;163:462-9.)
C1 [Reynolds, Harmony R.; Pearte, Camille A.; Hochman, Judith S.] NYU, Sch Med, Cardiovasc Clin Res Ctr, New York, NY USA.
   [Forman, Sandra A.; Liu, Li] Clin Trials & Surveys Corp, Owings Mills, MD USA.
   [Tamis-Holland, Jacqueline E.] St Lukes Roosevelt Hosp, New York, NY USA.
   [Tamis-Holland, Jacqueline E.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA.
   [Steg, Philippe Gabriel] Univ Paris 07, Paris, France.
   [Steg, Philippe Gabriel] Hop Bichat Claude Bernard, AP HP, INSERM U 698, Dept Cardiol, F-75877 Paris, France.
   [Mark, Daniel B.] Duke Univ, Duke Clin Res Inst, Durham, NC USA.
   [Carvalho, Antonio C.] Hosp Sao Paulo, UNIFESP, Sao Paulo, Brazil.
   [Sopko, George] NHLBI, Bethesda, MD 20892 USA.
   [Lamas, Gervasio A.] Columbia Univ, Div Cardiol, Mt Sinai Med Ctr, Miami Beach, FL USA.
   [Kruk, Mariusz; Ruzyllo, Witold] Natl Inst Cardiol, Warsaw, Poland.
   [Loboz-Grudzien, Krystyna] Wroclaw Med Univ, T Marciniak Hosp, Wroclaw, Poland.
RP Reynolds, HR (reprint author), 530 1st Ave,Suite 9R, New York, NY 10016 USA.
EM harmony.reynolds@nyumc.org
RI Liu, Li/K-1936-2012; Reynolds, Harmony/M-4818-2013; 
OI Liu, Li/0000-0002-5054-2372; Mark, Daniel/0000-0001-6340-8087; Reynolds,
   Harmony/0000-0003-0284-0655; Hochman, Judith/0000-0002-5889-5981
FU National Heart, Lung, and Blood Institute, National Institutes of Health
   [U01 HL062509, U01 HL062511, U01 HL062257]; Eli Lilly; Bristol Myers
   Squibb Medical Imaging; Bristol Myers Squibb; Schering-Plough;
   Medtronic, Inc; Sanofi-Aventis
FX OAT was supported by grants (U01 HL062509, U01 HL062511, U01 HL062257)
   from the National Heart, Lung, and Blood Institute, National Institutes
   of Health.; Dr Hochman received grant support to her institution from
   Eli Lilly and Bristol Myers Squibb Medical Imaging and product donation
   from Millennium Pharmaceuticals, Schering-Plough, Guidant, and Merck for
   OAT; consultation fees from Bristol Myers Squibb; honoraria for Steering
   Committee service from CV Therapeutics, Eli Lilly, and GlaxoSmithKline;
   and honoraria for serving on the Data Safety Monitoring Board of a trial
   supported by Schering-Plough. Dr Mark received grant support from
   Medtronic, Inc, Modest ownership interest in GDS and is a consultant for
   CVT and Astra-Zeneca. Dr Steg received research support from
   Sanofi-Aventis; is a speaker for Boehringer-Ingelheim, BMS, GSK,
   Medtronic, Nycomed, Sanofi-Aventis, and Servier; and is a member of the
   advisory board for Astellas, Astra-Zeneca, Bayer, Boehringer-Ingelheim,
   BMS, Endotis, GSK, Medtronic, MSD, Nycomed, Sanofi-Aventis, Servier, and
   The Medicines Company.
NR 22
TC 3
Z9 3
U1 0
U2 5
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
J9 AM HEART J
JI Am. Heart J.
PD MAR
PY 2012
VL 163
IS 3
BP 462
EP 469
DI 10.1016/j.ahj.2012.01.005
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 909WO
UT WOS:000301597200023
PM 22424018
ER

PT J
AU Parikh, NI
   Lloyd-Jones, DM
   Ning, HY
   Ouyang, P
   Polak, JF
   Lima, JA
   Bluemke, D
   Mittleman, MA
AF Parikh, Nisha I.
   Lloyd-Jones, Donald M.
   Ning, Hongyan
   Ouyang, Pamela
   Polak, Joseph F.
   Lima, Joao A.
   Bluemke, David
   Mittleman, Murray A.
TI Association of number of live births with left ventricular structure and
   function. The Multi-Ethnic Study of Atherosclerosis (MESA)
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID CORONARY HEART-DISEASE; GESTATIONAL DIABETES-MELLITUS;
   CARDIOVASCULAR-DISEASE; PERIPARTUM CARDIOMYOPATHY; RISK-FACTORS; WOMEN;
   PARITY; PREGNANCY; FAILURE; EPIDEMIOLOGY
AB Background Pregnancy is associated with marked maternal cardiovascular/hemodynamic changes. A greater number of pregnancies may be associated with long-term subclinical changes in left ventricular (LV) remodeling.
   Methods Among 2,234 white, black, Hispanic, and Chinese women (mean age 62 years) in the MESA, we used linear regression to relate live births and cardiac magnetic resonance imaging LV measures. Covariates included age, ethnicity, height, income, education, birth country, smoking, menopause, and oral contraceptive duration. Models were additionally adjusted for potential mediators: systolic blood pressure, antihypertensive use, total/high-density lipoprotein cholesterol, triglycerides, diabetes, and body mass index. We performed sensitivity analyses excluding 763 women in the lowest socioeconomic group: annual income <$25,000 and lower high school level of education.
   Results With each live birth, LV mass increased 1.26 g; LV end-diastolic volume, 0.74 mL; and LV end-systolic volume, 0.45 mL; LV ejection fraction decreased 0.18% (P trend <0.05). Changes were most notable for the category of women with >= 5 pregnancies. Upon adjustment for potential biologic mediators, live births remained positively associated with LV mass and end-systolic volume. Live births remained significantly associated with LV end-systolic, end-diastolic volumes, and LV mass (P trend <= 0.02) after excluding women in the lowest socioeconomic group.
   Conclusions Number of live births is associated with key LV structural and functional measures in middle to older ages, even after adjustment for sociodemographic factors and cardiovascular disease risk factors. Hemodynamic changes during pregnancy may be associated with cardiac structure/function beyond childbearing years. (Am Heart J 2012;163:470-6.)
C1 [Parikh, Nisha I.] Univ Hawaii, Div Cardiol, Queens Med Ctr, Honolulu, HI 96813 USA.
   [Parikh, Nisha I.] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96813 USA.
   [Lloyd-Jones, Donald M.; Ning, Hongyan] Northwestern Univ, Dept Prevent Med, Baltimore, MD USA.
   [Ouyang, Pamela] Johns Hopkins Univ, Dept Med, Div Cardiol, Baltimore, MD USA.
   [Polak, Joseph F.] Tufts Med Ctr, Div Radiol, Boston, MD USA.
   [Lima, Joao A.] Johns Hopkins Univ, Div Cardiol & Radiol, Baltimore, MD USA.
   [Bluemke, David] NIH, Ctr Clin, Bethesda, MD 20892 USA.
   [Bluemke, David] Natl Inst Biomed Imaging & Bioengn, Bethesda, MD USA.
   [Mittleman, Murray A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Cardiovasc, Sch Med,Dept Med, Boston, MA 02215 USA.
   [Mittleman, Murray A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Cardiovasc Epidemiol & Res Unit,Dept Med, Boston, MA 02215 USA.
RP Parikh, NI (reprint author), Univ Hawaii, Div Cardiol, Queens Med Ctr, Honolulu, HI 96813 USA.
EM nparikh@queens.org
RI Lloyd-Jones, Donald/C-5899-2009; 
OI Bluemke, David/0000-0002-8323-8086
FU NHLBI NIH HHS [F32 HL096390-01]; NIMHD NIH HHS [U54 MD007584]
NR 39
TC 6
Z9 6
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
J9 AM HEART J
JI Am. Heart J.
PD MAR
PY 2012
VL 163
IS 3
BP 470
EP 476
DI 10.1016/j.ahj.2011.12.011
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 909WO
UT WOS:000301597200024
PM 22424019
ER

PT J
AU Brau-Javier, CN
   Gonzales-Chavez, J
   Toro, JR
AF Brau-Javier, Cristina N.
   Gonzales-Chavez, Jose
   Toro, Jorge R.
TI Chronic Cutaneous Pustulosis Due to a 175-kb Deletion on Chromosome 2q13
   Excellent Response to Anakinra
SO ARCHIVES OF DERMATOLOGY
LA English
DT Article
ID CONGENITAL DYSERYTHROPOIETIC ANEMIA; RECURRENT MULTIFOCAL OSTEOMYELITIS;
   AUTOINFLAMMATORY DISEASES; INFLAMMATORY DISEASE; PSORIASIS; DEFICIENCY;
   ANTAGONIST; MUTATIONS
AB Deficiency of interleukin 1 receptor antagonist (D1RA) is a newly described autosomal recessive autoin flammatory disease in which absence of interleukin 1 (IL-1) receptor antagonist allows unopposed IL-1 activation, resulting in life-threatening systemic inflammation with prominent skin and bone involvement. We present a case of chronic cutaneous pustulosis treated with anakinra, a recombinant IL-1 receptor antagonist, resulting in rapid and significant clinical improvement.
C1 [Toro, Jorge R.] NCI, Div Canc Epidemiol & Genet, Genet Epidemiol Branch, Bethesda, MD 20892 USA.
   [Brau-Javier, Cristina N.; Gonzales-Chavez, Jose] Univ Puerto Rico, Dept Dermatol, San Juan, PR 00936 USA.
RP Toro, JR (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Execut Plaza S,Room 7012, Rockville, MD 20892 USA.
EM toroj@mail.nih.gov
FU (Division of Cancer Epidemiology and Genetics) of the National Cancer
   Institute
FX This study was supported in part by federal funds from the Intramural
   programs (Division of Cancer Epidemiology and Genetics) of the National
   Cancer Institute.
NR 11
TC 14
Z9 14
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-987X
J9 ARCH DERMATOL
JI Arch. Dermatol.
PD MAR
PY 2012
VL 148
IS 3
BP 301
EP 304
PG 4
WC Dermatology
SC Dermatology
GA 911BV
UT WOS:000301693200003
PM 22431772
ER

PT J
AU Cowen, EW
   Goldbach-Mansky, R
AF Cowen, Edward W.
   Goldbach-Mansky, Raphaela
TI DIRA, DITRA, and New Insights Into Pathways of Skin Inflammation What's
   in a Name?
SO ARCHIVES OF DERMATOLOGY
LA English
DT Editorial Material
ID GENERALIZED PUSTULAR PSORIASIS; NF-KAPPA-B; INTERLEUKIN-1-RECEPTOR
   ANTAGONIST; AUTOINFLAMMATORY DISEASE; MEMBERS; IL-1; DEFICIENCY; FAMILY;
   IL1RN; MUTATIONS
C1 [Cowen, Edward W.] NIH, Dermatol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Goldbach-Mansky, Raphaela] NIAMSD, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD 20892 USA.
RP Cowen, EW (reprint author), NIH, Dermatol Branch, Ctr Canc Res, 10 Ctr Dr,MSC 1908,Bldg 10,Room 12N238, Bethesda, MD 20892 USA.
EM cowene@mail.nih.gov
FU Intramural NIH HHS [ZIA AR041138-08]
NR 25
TC 18
Z9 19
U1 0
U2 4
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-987X
J9 ARCH DERMATOL
JI Arch. Dermatol.
PD MAR
PY 2012
VL 148
IS 3
BP 381
EP 384
PG 4
WC Dermatology
SC Dermatology
GA 911BV
UT WOS:000301693200015
PM 22431779
ER

PT J
AU Kebebew, E
AF Kebebew, Electron
TI Robotic Posterior Retroperitoneal Adrenalectomy For What Benefit and at
   What Cost?
SO ARCHIVES OF SURGERY
LA English
DT Editorial Material
ID ASSISTED UNILATERAL ADRENALECTOMIES
C1 NCI, Endocrine Oncol Sect, Surg Branch, Bethesda, MD 20892 USA.
RP Kebebew, E (reprint author), NCI, Endocrine Oncol Sect, Surg Branch, 10 Ctr Dr,MSC 1201,Bldg 10-CRC,Rm 3-3940, Bethesda, MD 20892 USA.
EM kebebewe@mail.nih.gov
NR 4
TC 0
Z9 0
U1 1
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0004-0010
J9 ARCH SURG-CHICAGO
JI Arch. Surg.
PD MAR
PY 2012
VL 147
IS 3
BP 275
EP 276
PG 2
WC Surgery
SC Surgery
GA 910LC
UT WOS:000301637200017
PM 22430912
ER

PT J
AU Mollapour, M
   Neckers, L
AF Mollapour, Mehdi
   Neckers, Len
TI Post-translational modifications of Hsp90 and their contributions to
   chaperone regulation
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
LA English
DT Review
DE Heat shock protein 90; Hsp82; Post-translational modification;
   phosphotylation; Acetylation; Oxidation; Nitrosylation
ID HEAT-SHOCK-PROTEIN; CASEIN KINASE-II; IN-VITRO PHOSPHORYLATION; CELLULAR
   FKBP52 PROTEIN; MOLECULAR CHAPERONE; CO-CHAPERONE;
   SACCHAROMYCES-CEREVISIAE; ATPASE ACTIVITY; CANCER-CELLS; TYROSINE
   PHOSPHORYLATION
AB Molecular chaperones, as the name suggests, are involved in folding, maintenance, intracellular transport, and degradation of proteins as well as in facilitating cell signaling. Heat shock protein 90 (Hsp90) is an essential eukaryotic molecular chaperone that carries out these processes in normal and cancer cells. Hsp90 function in vivo is coupled to its ability to hydrolyze ATP and this can be regulated by co-chaperones and post-translational modifications. In this review, we explore the varied roles of known post-translational modifications of cytosolic and nuclear Hsp90 (phosphorylation, acetylation, S-nitrosylation, oxidation and ubiquitination) in fine-tuning chaperone function in eukaryotes. This article is part of a Special Issue entitled: Heat Shock Protein 90 (HSP90). Published by Elsevier B.V.
C1 [Mollapour, Mehdi; Neckers, Len] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Mollapour, M (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM mollapourm@mail.nih.gov; neckers@nih.gov
FU NIH; National Cancer Institute; Center for Cancer Research
FX We are grateful to our colleagues Shinji Tsutsumi, Wanping Xu, Kristin
   Beebe, Bradley Scroggins, and our collaborators Jane Trepel, Laurence H.
   Pearl, Peter W. Piper, Chris Prodromou, Johannes Buchner, Matthias
   Mayer, Brian Blagg, William G. Stetler-Stevenson, Giorgio Colombo, Barry
   Panaretou, Dimitra Bourboulia, Min-Jung Lee, Giulia Morra, Sunmin Lee,
   Alison Donnelly, Cara Vaughan, and Andrew Truman for their scientific
   contributions and stimulating discussions. Our research in this field
   benefits from the support of the Intramural Research Program of the NIH,
   National Cancer Institute, Center for Cancer Research.
NR 138
TC 95
Z9 96
U1 3
U2 26
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-4889
J9 BBA-MOL CELL RES
JI Biochim. Biophys. Acta-Mol. Cell Res.
PD MAR
PY 2012
VL 1823
IS 3
SI SI
BP 648
EP 655
DI 10.1016/j.bbamcr.2011.07.018
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 910HV
UT WOS:000301628700006
PM 21856339
ER

PT J
AU Mitsunaga, M
   Nakajima, T
   Sano, K
   Choyke, PL
   Kobayashi, H
AF Mitsunaga, Makoto
   Nakajima, Takahito
   Sano, Kohei
   Choyke, Peter L.
   Kobayashi, Hisataka
TI Near-infrared Theranostic Photoimmunotherapy (PIT): Repeated Exposure of
   Light Enhances the Effect of Immunoconjugate
SO BIOCONJUGATE CHEMISTRY
LA English
DT Article
ID IN-VIVO; MONOCLONAL-ANTIBODY; CANCER; MOUSE; IMMUNOTHERAPY
AB Armed antibody-based targeted molecular therapies offer the possibility of effective tumor control with a minimum of side effects. Photoimmunotherapy (PIT) employs a monoclonal antibody-photo-toxic phthalocyanine dye, IR700 conjugate, that is activated by focal near-infrared (NIR) light irradiation after antibody binding to the targeted tumor cell surface leading to rapid necrotic cell death. Therapy by single NIR light irradiation was effective without significant side effects; however, recurrences were seen in most treated mice probably because of inhomogeneous distribution of panitumumab-IR700 immunoconjugate in the tumor, leading to ineffective PIT. We describe here an optimized regimen of effective PIT method for the same HER1-overexpressing tumor model (A431) with fractionated administration of panitumumab-IR700 conjugate followed by systematic repeated NIR light irradiation to the tumor based on timing of antibody redistribution into the remnant tumor under the guidance of IR700 fluorescence signal. Eighty percent of the A431 tumors were eradicated with repeated PIT without apparent side effects and survived tumor-free for more than 120 days even after stopping therapy at day 30. Therapeutic effects were monitored using IR700 fluorescent signal. PIT is a promising highly selective and clinically feasible theranostic method for treatment of mAb-binding tumors with minimal off-target effects.
C1 [Mitsunaga, Makoto; Nakajima, Takahito; Sano, Kohei; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM kobayash@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
   Cancer Research
FX This research was supported by the Intramural Research Program of the
   National Institutes of Health, National Cancer Institute, Center for
   Cancer Research.
NR 17
TC 55
Z9 55
U1 2
U2 22
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1043-1802
J9 BIOCONJUGATE CHEM
JI Bioconjugate Chem.
PD MAR
PY 2012
VL 23
IS 3
BP 604
EP 609
DI 10.1021/bc200648m
PG 6
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
   Chemistry, Multidisciplinary; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 911EN
UT WOS:000301700200032
PM 22369484
ER

PT J
AU Engmann, C
   Garces, A
   Jehan, I
   Ditekemena, J
   Phiri, M
   Thorsten, V
   Mazariegos, M
   Chomba, E
   Pasha, O
   Tshefu, A
   Wallace, D
   McClure, EM
   Goldenberg, RL
   Carlo, WA
   Wright, LL
   Bose, C
AF Engmann, C.
   Garces, A.
   Jehan, I.
   Ditekemena, J.
   Phiri, M.
   Thorsten, V.
   Mazariegos, M.
   Chomba, E.
   Pasha, O.
   Tshefu, A.
   Wallace, D.
   McClure, E. M.
   Goldenberg, R. L.
   Carlo, W. A.
   Wright, L. L.
   Bose, C.
TI Birth attendants as perinatal verbal autopsy respondents in low- and
   middle-income countries: a viable alternative?
SO BULLETIN OF THE WORLD HEALTH ORGANIZATION
LA English
DT Article
ID 4-MILLION NEONATAL DEATHS; SUB-SAHARAN AFRICA; ADULT MORTALITY;
   STILLBIRTHS; COMMUNITY; CHALLENGES
AB Objective To assess the feasibility of using birth attendants instead of bereaved mothers as perinatal verbal autopsy respondents.
   Methods Verbal autopsy interviews for early neonatal deaths and stillbirths were conducted separately among mothers (reference standard) and birth attendants in 38 communities in four developing countries. Concordance between maternal and attendant responses was calculated for all questions, for categories of questions and for individual questions. The sensitivity and specificity of individual questions with the birth attendant as respondent were assessed.
   Findings For early neonatal deaths, concordance across all questions was 94%. Concordance was at least 95% for more than half the questions on maternal medical history, birth attendance and neonate characteristics. Concordance on any given question was never less than 80%. Sensitivity and specificity varied across individual questions, more than 80% of which had a sensitivity of at least 80% and a specificity of at least 90%.
   For stillbirths, concordance across all questions was 93%. Concordance was 95% or greater more than half the time for questions on birth attendance, site of delivery and stillborn characteristics. Sensitivity and specificity varied across individual questions. Over 60% of the questions had a sensitivity of at least 80% and over 80% of them had a specificity of at least 90%. Overall, the causes of death established through verbal autopsy were similar, regardless of respondent.
   Conclusion Birth attendants can substitute for bereaved mothers as verbal autopsy respondents. The questions in existing harmonized verbal autopsy questionnaires need further refinement, as their sensitivity and specificity differ widely.
C1 [Engmann, C.; Bose, C.] Univ N Carolina, Sch Med, Dept Pediat & Maternal & Child Hlth, UNC Hosp, Chapel Hill, NC 27599 USA.
   [Engmann, C.; Bose, C.] Univ N Carolina, Sch Publ Hlth, Dept Pediat & Maternal & Child Hlth, UNC Hosp, Chapel Hill, NC 27599 USA.
   [Garces, A.] San Carlos Univ, Inst Multidisciplinario Salud IMSALUD, Guatemala City, Guatemala.
   [Jehan, I.; Pasha, O.] Aga Khan Univ, Karachi, Pakistan.
   [Ditekemena, J.; Tshefu, A.] Kinshasa Sch Publ Hlth, Kinshasa, Zaire.
   [Phiri, M.; Chomba, E.] Univ Teaching Hosp, Lusaka, Zambia.
   [Thorsten, V.; Wallace, D.; McClure, E. M.] Res Triangle Inst, Durham, NC USA.
   [Mazariegos, M.] Inst Nutr Cent Amer & Panama, Guatemala City, Guatemala.
   [Goldenberg, R. L.] Drexel Univ, Philadelphia, PA 19104 USA.
   [Carlo, W. A.] Univ Alabama Birmingham, Birmingham, AL USA.
   [Wright, L. L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Engmann, C (reprint author), Univ N Carolina, Sch Med, Dept Pediat & Maternal & Child Hlth, UNC Hosp, CB 7596,4th Floor, Chapel Hill, NC 27599 USA.
EM cengmann@med.unc.edu
FU National Institutes of Child Health and Human Development [U01 HD043475,
   U01 HD040636, U01 HD043464, U01 HD040607, U01 HD040657, U01
   HD043475-03S1]
FX Funding was provided by grants from the National Institutes of Child
   Health and Human Development (U01 HD043475, U01 HD040636, U01 HD043464,
   U01 HD040607, U01 HD040657 and U01 HD043475-03S1).
NR 30
TC 3
Z9 3
U1 1
U2 1
PU WORLD HEALTH ORGANIZATION
PI GENEVA 27
PA MARKETING AND DISSEMINATION, CH-1211 GENEVA 27, SWITZERLAND
SN 0042-9686
J9 B WORLD HEALTH ORGAN
JI Bull. World Health Organ.
PD MAR
PY 2012
VL 90
IS 3
BP 200
EP 208
DI 10.2471/BLT.11.092452
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 908BV
UT WOS:000301466300011
PM 22461715
ER

PT J
AU Korpershoek, E
   Pacak, K
   Martiniova, L
AF Korpershoek, Esther
   Pacak, Karel
   Martiniova, Lucia
TI Murine Models and Cell Lines for the Investigation of Pheochromocytoma:
   Applications for Future Therapies?
SO ENDOCRINE PATHOLOGY
LA English
DT Article
DE Pheochromocytoma; Knock-out mice; Animal models; Pheochromocytoma cell
   line; Imaging; Treatment
ID NEUROFIBROMATOSIS KNOCKOUT MICE; MULTIPLE ENDOCRINE NEOPLASIA;
   COMPARATIVE GENOMIC HYBRIDIZATION; TUMOR-SUPPRESSOR GENE;
   MEDULLARY-THYROID CARCINOMA; CDK INHIBITORS P18(INK4C); MALIGNANT
   PHEOCHROMOCYTOMAS; METASTATIC PHEOCHROMOCYTOMA; ALLELIC LOSS; SPORADIC
   PHEOCHROMOCYTOMAS
AB Pheochromocytomas (PCCs) are slow-growing neuroendocrine tumors arising from adrenal chromaffin cells. Tumors arising from extra-adrenal chromaffin cells are called paragangliomas. Metastases can occur up to approximately 60% or even more in specific subgroups of patients. There are still no well-established and clinically accepted "metastatic" markers available to determine whether a primary tumor is or will become malignant. Surgical resection is the most common treatment for non-metastatic PCCs, but no standard treatment/regimen is available for metastatic PCC. To investigate what kind of therapies are suitable for the treatment of metastatic PCC, animal models or cell lines are very useful. Over the last two decades, various mouse and rat models have been created presenting with PCC, which include models presenting tumors that are to a certain degree biochemically and/or molecularly similar to human PCC, and develop metastases. To be able to investigate which chemotherapeutic options could be useful for the treatment of metastatic PCC, cell lines such as mouse pheochromocytoma (MPC) and mouse tumor tissue (MTT) cells have been recently introduced and they both showed metastatic behavior. It appears these MPC and MTT cells are biochemically and molecularly similar to some human PCCs, are easily visualized by different imaging techniques, and respond to different therapies. These studies also indicate that some mouse models and both mouse PCC cell lines are suitable for testing new therapies for metastatic PCC.
C1 [Korpershoek, Esther] Erasmus MC Univ, Med Ctr Rotterdam, Josephine Nefkens Inst, Dept Pathol, NL-3000 CA Rotterdam, Netherlands.
   [Pacak, Karel; Martiniova, Lucia] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
RP Korpershoek, E (reprint author), Erasmus MC Univ, Med Ctr Rotterdam, Josephine Nefkens Inst, Dept Pathol, Room Ae304,POB 2040, NL-3000 CA Rotterdam, Netherlands.
EM e.korpershoek.1@erasmusmc.nl
FU Eunice Kennedy Shriver National Institutes of Child Health and Human
   Development, National Institutes of Health
FX This research was supported (in part) by the Intramural Research Program
   of the Eunice Kennedy Shriver National Institutes of Child Health and
   Human Development, National Institutes of Health. The authors have no
   conflict of interest to disclose.
NR 101
TC 12
Z9 12
U1 0
U2 3
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1046-3976
J9 ENDOCR PATHOL
JI Endocr. Pathol.
PD MAR
PY 2012
VL 23
IS 1
BP 43
EP 54
DI 10.1007/s12022-012-9194-y
PG 12
WC Endocrinology & Metabolism; Pathology
SC Endocrinology & Metabolism; Pathology
GA 912GR
UT WOS:000301784200006
PM 22323007
ER

PT J
AU Cupul-Uicab, LA
   Skjaerven, R
   Haug, K
   Melve, KK
   Engel, SM
   Longnecker, MP
AF Cupul-Uicab, Lea A.
   Skjaerven, Rolv
   Haug, Kjell
   Melve, Kari K.
   Engel, Stephanie M.
   Longnecker, Matthew P.
TI In Utero Exposure to Maternal Tobacco Smoke and Subsequent Obesity,
   Hypertension, and Gestational Diabetes Among Women in the MoBa Cohort
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE diabetes mellitus; gestational diabetes; hypertension; in utero;
   maternal smoking; MoBa; obesity; tobacco smoke
ID BODY-MASS INDEX; BLOOD-PRESSURE; DEVELOPMENTAL ORIGINS; METABOLIC
   SYNDROME; PARENTAL SMOKING; NORWEGIAN MOTHER; BIRTH-WEIGHT; CHILD
   COHORT; LIFE-COURSE; PREGNANCY
AB BACKGROUND: Environmental factors influencing the developmental origins of health and disease need to be identified and investigated. In utero exposure to tobacco smoke has been associated with obesity and a small increase in blood pressure in children; however, whether there is a corresponding increased risk of conditions such as diabetes and hypertension during adulthood remains unclear.
   OBJECTIVE: Our goal was to assess the association of self-reported in utero exposure to tobacco smoke with the prevalence of obesity, hypertension, type 2 diabetes mellitus (T2DM), and gestational diabetes mellitus (GDM) in women 14-47 years of age.
   METHODS: We conducted a cross-sectional analysis of the Norwegian Mother and Child Cohort Study, which enrolled pregnant women in Norway from 1999 thorough 2008. Exposure to tobacco smoke in utero (yes vs. no) was ascertained on the baseline questionnaire (obtained at 17 weeks' gestation); the outcomes were ascertained from the Medical Birth Registry of Norway and the questionnaire. Our analysis included 74,023 women.
   RESULTS: Women exposed to tobacco smoke in utero had 1.53 times the odds of obesity [95% confidence interval (CI): 1.45, 1.61] relative to those unexposed, after adjusting for age, education, and personal smoking. After further adjustment for body mass index, the odds ratio for hypertension was 1.68 (95% CI: 1.19, 2.39); for T2DM 1.14 (95% CI: 0.79, 1.65); and for GDM 1.32 (95% CI: 1.10, 1.58) among exposed compared with unexposed.
   CONCLUSIONS: Exposure to tobacco smoke in utero was associated with obesity, hypertension, and GDM in adult women. The possibility that the associations were attributable to unmeasured confounding cannot be excluded.
C1 [Cupul-Uicab, Lea A.; Longnecker, Matthew P.] Natl Inst Hlth, Epidemiol Branch, Natl Inst Environm Hlth Sci, Dept Hlth & Human Serv, Res Triangle Pk, NC USA.
   [Skjaerven, Rolv; Haug, Kjell; Melve, Kari K.] Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway.
   [Skjaerven, Rolv; Melve, Kari K.] Norwegian Inst Publ Hlth, Med Birth Registry Norway, Bergen, Norway.
   [Engel, Stephanie M.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
RP Cupul-Uicab, LA (reprint author), EB NIEHS, MD A3-05,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM cupuluicabl@niehs.nih.gov
RI CUPUL UICAB, LEA/C-8699-2014; 
OI CUPUL UICAB, LEA/0000-0001-6190-4474; Longnecker,
   Matthew/0000-0001-6073-5322
FU National Institutes of Health (NIH), National Institute of Environmental
   Health Sciences (NIEHS); Norwegian Ministry of Health [N01-ES-75558];
   NIH/NIEHS; NIH/NINDS [1 UO1 NS 047537-01]; Norwegian Research
   Council/FUGE [151918/S10]; NIH/NICHD [1R01HD058008]
FX This research was supported in part by the Intramural Research Program
   of the National Institutes of Health (NIH), National Institute of
   Environmental Health Sciences (NIEHS). The Norwegian Mother and Child
   Cohort Study is supported by the Norwegian Ministry of Health, contract
   N01-ES-75558 with NIH/NIEHS, NIH/NINDS (grant 1 UO1 NS 047537-01), and
   the Norwegian Research Council/FUGE (grant 151918/S10). The validation
   substudy is supported by NIH/NICHD (grant 1R01HD058008).
NR 45
TC 27
Z9 29
U1 0
U2 9
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
   RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD MAR
PY 2012
VL 120
IS 3
BP 355
EP 360
DI 10.1289/ehp.1103789
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health;
   Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health; Toxicology
GA 907CF
UT WOS:000301394700021
PM 22128036
ER

PT J
AU D'Aloisio, AA
   Baird, DD
   DeRoo, LA
   Sandler, DP
AF D'Aloisio, Aimee A.
   Baird, Donna D.
   DeRoo, Lisa A.
   Sandler, Dale P.
TI Early-Life Exposures and Early-Onset Uterine Leiomyomata in Black Women
   in the Sister Study
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE diabetes mellitus; diethylstilbestrol; early-life; leiomyoma; multiple
   birth offspring; pregnancy; pregnancy-induced hypertension; prenatal
   exposure delayed effects; socioeconomic factors; soy formula
ID REPRODUCTIVE FACTORS; RISK; AGE; DIETHYLSTILBESTROL; IDENTIFICATION;
   EPIDEMIOLOGY; FIBROIDS; HEALTH; PERIOD; RATES
AB BACKGROUND: Uterine leiomyomata (fibroids) are hormonally responsive tumors, but little is known about risk factors. Early-life exposures may influence uterine development and subsequent response to hormones in adulthood. An earlier analysis of non-Hispanic white women who participated in the Sister Study found associations between several early-life factors and early-onset fibroids.
   OBJECTIVES: We evaluated associations of early-life and childhood exposures with early-onset fibroids among black women and compared the results with those found among white women.
   METHODS: We analyzed baseline data from 3,534 black women, 35-59 years of age, in the Sister Study (a nationwide cohort of women who had a sister diagnosed with breast cancer) who self-reported information on early-life and childhood exposures. Early-onset fibroids were assessed based on self-report of a physician diagnosis of fibroids by the age of 30 years (n = 561). We estimated risk ratios (RR) and 95% confidence intervals (Cl) from log-binomial regression models.
   RESULTS: Factors most strongly associated with early-onset fibroids were in utero diethylstilbestrol (DES; RR = 2.02; 95% Cl: 1.28, 3.18), maternal prepregnancy diabetes or gestational diabetes (RR = 1.54; 95% CI: 0.95, 2.49), and monozygotic multiple birth (RR = 1.94; 95% CI: 1.26, 2.99). We also found positive associations with having been taller or thinner than peers at the age of 10 years and with early-life factors that included being the firstborn child of a teenage mother, maternal hypertensive disorder, preterm birth, and having been fed soy formula.
   CONCLUSIONS: With the exception of monozygotic multiple birth and maternal hypertensive disorder, early-life risk factors for early-onset fibroids for black women were similar to those found for white women. However, in contrast to whites, childhood height and weight, but not low socioeconomic status indicators, were associated with early-onset fibroids in blacks. The general consistency of early-life findings for black and white women supports a possible role of early-life factors in fibroid development.
C1 [D'Aloisio, Aimee A.] Natl Inst Hlth, Natl Inst Environm Hlth Sci, Dept Hlth, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
   Human Serv, Res Triangle Pk, NC USA.
RP D'Aloisio, AA (reprint author), Natl Inst Hlth, Natl Inst Environm Hlth Sci, Dept Hlth, Epidemiol Branch, POB 12233,Mail Drop A3-05,111 T W Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM daloisio@niehs.nih.gov
RI Baird, Donna/D-5214-2017; 
OI Baird, Donna/0000-0002-5544-2653; Sandler, Dale/0000-0002-6776-0018
FU National Institutes of Health, National Institute of Environmental
   Health Sciences [Z01 ES044005]
FX This research was supported by the Intramural Research Program of the
   National Institutes of Health, National Institute of Environmental
   Health Sciences (Z01 ES044005).
NR 33
TC 17
Z9 18
U1 2
U2 6
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
   RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD MAR
PY 2012
VL 120
IS 3
BP 406
EP 412
DI 10.1289/ehp.1103620
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health;
   Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health; Toxicology
GA 907CF
UT WOS:000301394700029
PM 22049383
ER

PT J
AU Trabert, B
   Longnecker, MP
   Brock, JW
   Klebanoff, MA
   McGlynn, KA
AF Trabert, Britton
   Longnecker, Matthew P.
   Brock, John W.
   Klebanoff, Mark A.
   McGlynn, Katherine A.
TI Maternal Pregnancy Levels of trans-Nonachlor and Oxychlordane and
   Prevalence of Cryptorchidism and Hypospadias in Boys
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE chlordanes; cryptorchidism; hypospadias; oxychlordane; pregnant women;
   prospective cohort; trans-nonachlor
ID POLYCHLORINATED-BIPHENYLS; PESTICIDES; POPULATION; CHLORDANE; RISK
AB BACKGROUND: The etiologies of the male urogenital anomalies cryptorchidism and hypospadias are poorly understood. Given positive associations between chlordane isomers and testicular germ cell tumors, it is reasonable to assume that chlordanes might also be associated with other testicular dysgenesis syndrome disorders, namely cryptorchidism and hypospadias.
   OBJECTIVE: To examine whether exposure to in utero chlordane is related to cryptorchidism and hypospadias, we evaluated levels of chlordane derivatives, trans-nonachlor and oxychlordane, among pregnant women enrolled in the Collaborative Perinatal Project (CPP).
   METHODS: From 1959 to 1965, the CPP enrolled pregnant women at 12 U.S. medical centers. We analyzed serum trans-nonachlor and oxychlordane levels measured in third-trimester serum from the mothers of 217 sons with cryptorchidism, 197 sons with hypospadias, and 557 sons with neither condition. Adjusted odds ratios (ORs) and 95% confidence intervals were calculated using conditional logistic regression.
   RESULTS: The quartile-specific ORs for cryptorchidism or hypospadias show no notable associations with trans-nonachlor or oxychlordane. Further, there were no significant trends with increasing quartile of maternal tram-nonachlor or oxychlordane level in either cryptorchidism or hypospadias (p-trend all > 0.45).
   CONCLUSIONS: The results do not support an association between chlordane levels and cryptorchidism or hypospadias. It is unlikely that current chlordane exposure is related to the development of either anomaly, given that serum chlordane levels at the time of sample collection, the early 1960s, were considerably higher than levels at present.
C1 [Trabert, Britton; McGlynn, Katherine A.] Natl Canc Inst, NIH, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch,DHHS, Rockville, MD 20852 USA.
   [Longnecker, Matthew P.] Natl Inst Environm Hlth Sci, Natl Inst Hlth, DHHS, Epidemiol Branch, Res Triangle Pk, NC USA.
   [Brock, John W.] Natl Ctr Environm Hlth, Ctr Dis Control & Prevent, Atlanta, GA USA.
   [Brock, John W.] Warren Wilson Coll, Dept Environm Studies, Asheville, NC USA.
   [Brock, John W.] Warren Wilson Coll, Dept Chem, Asheville, NC USA.
   [Klebanoff, Mark A.] Nationwide Childrens Hosp, Res Inst, Ctr Perinatal Res, Columbus, OH USA.
RP Trabert, B (reprint author), Natl Canc Inst, NIH, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch,DHHS, 6120 Executive Blvd,Suite 550, Rockville, MD 20852 USA.
EM britton.trabert@nih.gov
RI Trabert, Britton/F-8051-2015; 
OI Longnecker, Matthew/0000-0001-6073-5322
FU National Cancer Institute; Eunice Kennedy Shriver National Institute of
   Child Health and Human Development; National Institute of Environmental
   Health Sciences of the National Institutes of Health
FX Support for this research was provided by the Intramural Research
   Programs of the National Cancer Institute, the Eunice Kennedy Shriver
   National Institute of Child Health and Human Development, and the
   National Institute of Environmental Health Sciences of the National
   Institutes of Health.
NR 29
TC 12
Z9 12
U1 0
U2 3
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
   RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD MAR
PY 2012
VL 120
IS 3
BP 478
EP 482
DI 10.1289/ehp.1103936
PG 5
WC Environmental Sciences; Public, Environmental & Occupational Health;
   Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health; Toxicology
GA 907CF
UT WOS:000301394700040
PM 21975279
ER

PT J
AU Tilson, HA
   Schroeder, JC
   Booker, SM
AF Tilson, Hugh A.
   Schroeder, Jane C.
   Booker, Susan M.
TI The Future Is Now
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Editorial Material
C1 [Tilson, Hugh A.] NIEHS, EHP, NIH, Res Triangle Pk, NC 27709 USA.
RP Tilson, HA (reprint author), NIEHS, EHP, NIH, Mail Drop K3-01,POB 12233, Res Triangle Pk, NC 27709 USA.
EM tilsonha@niehs.nih.gov
OI Booker, Susan/0000-0002-3874-0800
NR 2
TC 0
Z9 0
U1 0
U2 1
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
   RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD MAR
PY 2012
VL 120
IS 3
BP A101
EP A101
DI 10.1289/ehp.1205032
PG 1
WC Environmental Sciences; Public, Environmental & Occupational Health;
   Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health; Toxicology
GA 907CF
UT WOS:000301394700001
ER

PT J
AU Ginsburg, AS
   Nahm, MH
   Khambaty, FM
   Alderson, MR
AF Ginsburg, Amy Sarah
   Nahm, Moon H.
   Khambaty, Farukh M.
   Alderson, Mark R.
TI Issues and challenges in the development of pneumococcal protein
   vaccines
SO EXPERT REVIEW OF VACCINES
LA English
DT Article
DE animal models; pneumococcal vaccine; protein; Streptococcus pneumoniae
ID NONTYPABLE HAEMOPHILUS-INFLUENZAE; CONJUGATE VACCINE;
   STREPTOCOCCUS-PNEUMONIAE; CHILDREN; DISEASE; ANTIBODIES; SEROTYPES
AB In view of the increasing licensure and use of pneumococcal conjugate vaccines, the relatively high cost, and growing issues with serotype emergence, there is a need to re-evaluate the role of pneumococcal protein vaccines (PPVs) and pathways to their licensure. This paper summarizes the discussion and viewpoints from an expert meeting regarding the development of PPVs. A wide spectrum of pneumococcal vaccine researchers, developers, and regulators met to review the state of PPVs, identify research and development needs, and provide consensus opinions to support the introduction of new PPVs where possible. They also discussed clinical and regulatory aspects pertinent to these vaccines and generated a series of recommendations for moving the field forward.
C1 [Ginsburg, Amy Sarah; Alderson, Mark R.] PATH, Seattle, WA USA.
   [Nahm, Moon H.] Univ Alabama, Birmingham, AL USA.
   [Khambaty, Farukh M.] NIH, Bethesda, MD 20892 USA.
RP Ginsburg, AS (reprint author), PATH, Seattle, WA USA.
EM aginsburg@path.org
OI Nahm, Moon/0000-0002-6922-1042
FU NIH [AI-30021]
FX The symposium was supported in part with funds from an NIH contract
   (AI-30021) to M Nahm. 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 23
TC 17
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U1 0
U2 3
PU EXPERT REVIEWS
PI LONDON
PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB,
   ENGLAND
SN 1476-0584
J9 EXPERT REV VACCINES
JI Expert Rev. Vaccines
PD MAR
PY 2012
VL 11
IS 3
BP 279
EP 285
DI 10.1586/ERV.12.5
PG 7
WC Immunology
SC Immunology
GA 911BP
UT WOS:000301692600009
PM 22380821
ER

PT J
AU Arlen, PM
   Wood, LV
AF Arlen, Philip M.
   Wood, Lauren V.
TI Prostate cancer vaccines: moving therapeutic vaccination forward in the
   post-Provenge (TM) era
SO EXPERT REVIEW OF VACCINES
LA English
DT Article
DE immune monitoring; prostate cancer; therapeutic vaccines
ID ALTERNATE READING FRAME; PHASE-III TRIAL; SIPULEUCEL-T;
   IONIZING-RADIATION; TUMOR VACCINES; SOLID TUMORS; CELLULAR
   IMMUNOTHERAPY; CTLA-4 BLOCKADE; CLINICAL-TRIALS; GENE-EXPRESSION
AB The focus of extensive research in the area of prostate cancer vaccines has led to the approval of the first therapeutic vaccine by the US FDA, sipuleucel-T. As our understanding of immunotherapy has increased, novel approaches have been investigated that have shown considerable promise. As the field has continued to evolve, questions have arisen regarding the potential role of immunotherapy: which populations of patients are most likely to benefit from immunotherapy and how and when should these therapies be administered? In addition, what are the best tools that can be used as surrogates to monitor immune responses to cancer vaccines that truly can give meaningful insight toward improving clinical outcomes? Finally, how can combination approaches be applied to prostate cancer vaccines in terms of both standard of care and experimental therapies? This review will address many of these important concepts with regard to prostate cancer vaccine therapy.
C1 [Wood, Lauren V.] NCI, Vaccine Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Arlen, Philip M.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Wood, LV (reprint author), NCI, Vaccine Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
EM woodl@mail.nih.gov
NR 107
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U1 0
U2 5
PU EXPERT REVIEWS
PI LONDON
PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB,
   ENGLAND
SN 1476-0584
J9 EXPERT REV VACCINES
JI Expert Rev. Vaccines
PD MAR
PY 2012
VL 11
IS 3
BP 287
EP 302
DI 10.1586/ERV.11.183
PG 16
WC Immunology
SC Immunology
GA 911BP
UT WOS:000301692600010
PM 22380822
ER

PT J
AU Azhar, MR
   Rahimi, Z
   Vaisi-Raygani, A
   Akramipour, R
   Madani, H
   Rahimi, Z
   Parsian, A
AF Azhar, Mohammad-Reza
   Rahimi, Zohreh
   Vaisi-Raygani, Asad
   Akramipour, Reza
   Madani, Hamid
   Rahimi, Ziba
   Parsian, Abbas
TI Lack of Association Between MTHFR C677T and A1298C Polymorphisms and
   Risk of Childhood Acute Lymphoblastic Leukemia in the Kurdish Population
   from Western Iran
SO GENETIC TESTING AND MOLECULAR BIOMARKERS
LA English
DT Article
ID METHYLENETETRAHYDROFOLATE REDUCTASE GENE; FOLATE; CHILDREN;
   SUSCEPTIBILITY; METAANALYSIS; HAPLOTYPES; GENOTYPES; PATHWAY; DISEASE;
   ADULTS
AB Aims: Polymorphism in genes involved in folate metabolism may influence the susceptibility to acute lymphoblastic leukemia (ALL). The aim of the present study was to determine the role of the two most common polymorphisms of the 5, 10-methylenetetrahydrofolate reductase (MTHFR) gene, MTHFR C677T and A1298C, and their interaction on the susceptibility to ALL. Methods: Seventy-two children with ALL and 109 age- and sex-matched healthy children from Western Iran were screened for MTHFR C677T and A1298C variants by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The frequencies of MTHFR 677T and 1298C alleles in patients were 29.9% and 43.1%, respectively, that were higher than those in controls (24.8% and 38.1%, respectively). Logistic regression analysis was performed and its result in the odds ratios (ORs) for possession of either MTHFR 677T or 1298C allele was found to be 1.98 [95% confidence interval (CI) 0.72-5.4, p = 0.18] and 1.48 (95% CI 0.59-3.69, p = 0.4), respectively. Also the concomitant presence of both MTHFR 677T and 1298C alleles was not associated with the risk of ALL [OR = 2.12 (95% CI 0.8-5.7, p = 0.13)]. Conclusion: Our results in a homogenous population with Kurdish ethnic background indicated that neither the MTHFR 677T allele nor the MTHFR 1298C allele is associated with increased risk of ALL.
C1 [Azhar, Mohammad-Reza; Rahimi, Zohreh; Rahimi, Ziba] Kermanshah Univ, Med Sci, Med Biol Res Ctr, Kermanshah 6714869914, Iran.
   [Azhar, Mohammad-Reza] Kermanshah Univ Med Sci, Sch Pharm, Kermanshah, Iran.
   [Rahimi, Zohreh; Vaisi-Raygani, Asad] Kermanshah Univ Med Sci, Sch Med, Dept Biochem, Kermanshah, Iran.
   [Akramipour, Reza] Kermanshah Univ Med Sci, Sch Med, Dept Pediat, Kermanshah, Iran.
   [Madani, Hamid] Kermanshah Univ Med Sci, Sch Med, Dept Pathol, Kermanshah, Iran.
   [Parsian, Abbas] NIAAA, Div Neurosci & Behav, NIH, Rockville, MD 20852 USA.
RP Rahimi, Z (reprint author), Kermanshah Univ, Med Sci, Med Biol Res Ctr, Daneshgah Ave, Kermanshah 6714869914, Iran.
EM zrahimi@kums.ac.ir; zrahimi@kums.ac.ir
OI Rahimi, Zohreh/0000-0001-7589-3307; Vaisi-Raygani,
   Asad/0000-0002-3042-2832
FU Kermanshah University of Medical Sciences, Kermanshah, Iran
FX This work was financially supported by a grant from Vice Chancellor for
   research of Kermanshah University of Medical Sciences, Kermanshah, Iran.
   This work was performed in partial fulfillment of the requirements for
   Pharm.D. of Mohammad-Reza Azhar, Kermanshah University of Medical
   Sciences, Kermanshah, Iran.
NR 31
TC 9
Z9 11
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1945-0265
J9 GENET TEST MOL BIOMA
JI Genet. Test. Mol. Biomark.
PD MAR
PY 2012
VL 16
IS 3
BP 198
EP 202
DI 10.1089/gtmb.2011.0041
PG 5
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 912EH
UT WOS:000301777000009
PM 22017305
ER

PT J
AU Lee, P
   Fu, YP
   Figueroa, JD
   Prokunina-Olsson, L
   Gonzalez-Bosquet, J
   Kraft, P
   Wang, ZM
   Jacobs, KB
   Yeager, M
   Horner, MJ
   Hankinson, SE
   Hutchinson, A
   Chatterjee, N
   Garcia-Closas, M
   Ziegler, RG
   Berg, CD
   Buys, SS
   McCarty, CA
   Feigelson, HS
   Thun, MJ
   Diver, R
   Prentice, R
   Jackson, R
   Kooperberg, C
   Chlebowski, R
   Lissowska, J
   Peplonska, B
   Brinton, LA
   Tucker, M
   Fraumeni, JF
   Hoover, RN
   Thomas, G
   Hunter, DJ
   Chanock, SJ
AF Lee, Phoebe
   Fu, Yi-Ping
   Figueroa, Jonine D.
   Prokunina-Olsson, Ludmila
   Gonzalez-Bosquet, Jesus
   Kraft, Peter
   Wang, Zhaoming
   Jacobs, Kevin B.
   Yeager, Meredith
   Horner, Marie-Josephe
   Hankinson, Susan E.
   Hutchinson, Amy
   Chatterjee, Nilanjan
   Garcia-Closas, Montserrat
   Ziegler, Regina G.
   Berg, Christine D.
   Buys, Saundra S.
   McCarty, Catherine A.
   Feigelson, Heather Spencer
   Thun, Michael J.
   Diver, Ryan
   Prentice, Ross
   Jackson, Rebecca
   Kooperberg, Charles
   Chlebowski, Rowan
   Lissowska, Jolanta
   Peplonska, Beata
   Brinton, Louise A.
   Tucker, Margaret
   Fraumeni, Joseph F., Jr.
   Hoover, Robert N.
   Thomas, Gilles
   Hunter, David J.
   Chanock, Stephen J.
TI Fine mapping of 14q24.1 breast cancer susceptibility locus
SO HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; OVARIAN-CANCER; RISK; ALLELES; LINKAGE;
   PROTEIN; REPAIR; COMMON; MUTATIONS; COMPLEX
AB In the National Cancer Institute Cancer Genetic Markers of Susceptibility (CGEMS) genome-wide association study of breast cancer, a single nucleotide polymorphism (SNP) marker, rs999737, in the 14q24.1 interval, was associated with breast cancer risk. In order to fine map this region, we imputed a 3.93 MB region flanking rs999737 for Stages 1 and 2 of the CGEMS study (5,692 cases, 5,576 controls) using the combined reference panels of the HapMap 3 and the 1000 Genomes Project. Single-marker association testing and variable-sized sliding-window haplotype analysis were performed, and for both analyses the initial tagging SNP rs999737 retained the strongest association with breast cancer risk. Investigation of contiguous regions did not reveal evidence for an additional independent signal. Therefore, we conclude that rs999737 is an optimal tag SNP for common variants in the 14q24.1 region and thus narrow the candidate variants that should be investigated in follow-up laboratory evaluation.
C1 [Lee, Phoebe; Fu, Yi-Ping; Figueroa, Jonine D.; Prokunina-Olsson, Ludmila; Wang, Zhaoming; Jacobs, Kevin B.; Yeager, Meredith; Horner, Marie-Josephe; Hutchinson, Amy; Chatterjee, Nilanjan; Garcia-Closas, Montserrat; Ziegler, Regina G.; Brinton, Louise A.; Tucker, Margaret; Fraumeni, Joseph F., Jr.; Hoover, Robert N.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
   [Gonzalez-Bosquet, Jesus] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Womens Oncol, Tampa, FL 33612 USA.
   [Kraft, Peter; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA.
   [Wang, Zhaoming; Jacobs, Kevin B.; Yeager, Meredith; Hutchinson, Amy] NCI Frederick, Core Genotyping Facil, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
   [Hankinson, Susan E.; Hunter, David J.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA.
   [Hankinson, Susan E.; Hunter, David J.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Berg, Christine D.] NCI, Canc Prevent Div, NIH, DHHS, Bethesda, MD 20892 USA.
   [Buys, Saundra S.] Univ Utah, Dept Internal Med, Salt Lake City, UT 84132 USA.
   [McCarty, Catherine A.] Marshfield Clin Res Fdn, Ctr Human Genet, Marshfield, WI 54449 USA.
   [Feigelson, Heather Spencer] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO 80237 USA.
   [Thun, Michael J.; Diver, Ryan] Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA.
   [Prentice, Ross; Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
   [Jackson, Rebecca] Ohio State Univ, Med Ctr, Div Diabet Endocrinol & Metab, Columbus, OH 43210 USA.
   [Chlebowski, Rowan] Harbor Univ Calif Los Angeles Med Ctr, Torrance, CA 90509 USA.
   [Lissowska, Jolanta] M Sklodowska Curie Mem, Ctr Canc, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
   [Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
   [Peplonska, Beata] Nofer Inst Occupat Med, Lodz, Poland.
   [Thomas, Gilles] Fdn Synergie Lyon Canc, Ctr Leon Berard, INSERM, U590, F-69373 Lyon, France.
   [Hunter, David J.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
RP Chanock, SJ (reprint author), NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
EM chanocks@mail.nih.gov
RI Peplonska, Beata/F-6004-2010; Berg , Christine/K-1047-2014; Tucker,
   Margaret/B-4297-2015; Garcia-Closas, Montserrat /F-3871-2015; Brinton,
   Louise/G-7486-2015; 
OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton,
   Louise/0000-0003-3853-8562; Prokunina-Olsson,
   Ludmila/0000-0002-9622-2091; Lissowska, Jolanta/0000-0003-2695-5799
FU NIH [CA 65725, CA87969, CA49449, CA67262, CA50385, 5UO1CA098233];
   National Heart, Lung and Blood Institute, NIH; Division of Cancer
   Epidemiology and Genetics; Division of Cancer Prevention, National
   Cancer Institute, NIH, DHHS;  [UO1 CA098710]
FX The Nurses' Health Studies are supported by NIH grants CA 65725,
   CA87969, CA49449, CA67262, CA50385 and 5UO1CA098233. The authors thank
   Barbara Egan, Lori Egan, Helena Judge Ellis, Hardeep Ranu, and Pati
   Soule for assistance, and the participants in the Nurses' Health
   Studies.; The WHI program is supported by contracts from the National
   Heart, Lung and Blood Institute, NIH. The authors thank the WHI
   investigators and staff for their dedication, and the study participants
   for making the program possible. A full listing of WHI investigators can
   be found at http://www.whi.org.; The ACS study is supported by UO1
   CA098710. We thank Cari Lichtman for data management and the
   participants on the CPS-II.; The PLCO study is supported by the
   Intramural Research Program of the Division of Cancer Epidemiology and
   Genetics and contracts from the Division of Cancer Prevention, National
   Cancer Institute, NIH, DHHS. The authors thank Dr Philip Prorok,
   Division of Cancer Prevention, National Cancer Institute; the Screening
   Center investigators and staff of the Prostate, Lung, Colorectal, and
   Ovarian Cancer Screening Trial (PLCO). Most importantly, we acknowledge
   the study participants for their contributions to making this study
   possible.
NR 35
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
J9 HUM GENET
JI Hum. Genet.
PD MAR
PY 2012
VL 131
IS 3
BP 479
EP 490
DI 10.1007/s00439-011-1088-4
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA 891YK
UT WOS:000300252700016
PM 21959381
ER

PT J
AU Bagci, U
   Chen, XJ
   Udupa, JK
AF Bagci, Ulas
   Chen, Xinjian
   Udupa, Jayaram K.
TI Hierarchical Scale-Based Multiobject Recognition of 3-D Anatomical
   Structures
SO IEEE TRANSACTIONS ON MEDICAL IMAGING
LA English
DT Article
DE Active shape model; graph-cut; image segmentation; intensity
   standardization; local scale; object recognition; principal component
   analysis; three-dimensional (3-D) shape models
ID IMAGE SEGMENTATION; GRAPH CUTS; INTENSITY STANDARDIZATION; INHOMOGENEITY
   CORRECTION; ALGORITHMS; REGISTRATION
AB Segmentation of anatomical structures from medical images is a challenging problem, which depends on the accurate recognition (localization) of anatomical structures prior to delineation. This study generalizes anatomy segmentation problem via attacking two major challenges: 1) automatically locating anatomical structures without doing search or optimization, and 2) automatically delineating the anatomical structures based on the located model assembly. For 1), we propose intensity weighted ball-scale object extraction concept to build a hierarchical transfer function from image space to object (shape) space such that anatomical structures in 3-D medical images can be recognized without the need to perform search or optimization. For 2), we integrate the graph-cut (GC) segmentation algorithm with prior shape model. This integrated segmentation framework is evaluated on clinical 3-D images consisting of a set of 20 abdominal CT scans. In addition, we use a set of 11 foot MR images to test the generalizability of our method to the different imaging modalities as well as robustness and accuracy of the proposed methodology. Since MR image intensities do not possess a tissue specific numeric meaning, we also explore the effects of intensity nonstandardness on anatomical object recognition. Experimental results indicate that: 1) effective recognition can make the delineation more accurate; 2) incorporating a large number of anatomical structures via a model assembly in the shape model improves the recognition and delineation accuracy dramatically; 3) ball-scale yields useful information about the relationship between the objects and the image; 4) intensity variation among scenes in an ensemble degrades object recognition performance.
C1 [Udupa, Jayaram K.] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA.
   [Bagci, Ulas] NIH, Ctr Infect Dis Imaging, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA.
   [Chen, Xinjian] Univ Iowa, Dept Elect & Comp Engn, Iowa City, IA 52242 USA.
RP Udupa, JK (reprint author), Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA.
RI Bagci, Ulas/A-4225-2012; Chen, Xinjian/E-8592-2016; 
OI Bagci, Ulas/0000-0001-7379-6829
FU National Institutes of Health [HL105212]
FX The work of J. K. Udupa was supported by the National Institutes of
   Health under Grant HL105212.
NR 44
TC 28
Z9 28
U1 2
U2 9
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0278-0062
EI 1558-254X
J9 IEEE T MED IMAGING
JI IEEE Trans. Med. Imaging
PD MAR
PY 2012
VL 31
IS 3
BP 777
EP 789
DI 10.1109/TMI.2011.2180920
PG 13
WC Computer Science, Interdisciplinary Applications; Engineering,
   Biomedical; Engineering, Electrical & Electronic; Imaging Science &
   Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging
SC Computer Science; Engineering; Imaging Science & Photographic
   Technology; Radiology, Nuclear Medicine & Medical Imaging
GA 904LM
UT WOS:000301198000022
PM 22203704
ER

PT J
AU Rodrigues, NP
   Tipping, AJ
   Wang, ZK
   Enver, T
AF Rodrigues, Neil P.
   Tipping, Alex J.
   Wang, Zhengke
   Enver, Tariq
TI GATA-2 mediated regulation of normal hematopoietic stem/progenitor cell
   function, myelodysplasia and myeloid leukemia
SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
LA English
DT Article
DE GATA-2; Hematopoietic stem cells; Myelodysplasia; Myeloid leukemia
ID TRANSCRIPTION FACTOR GATA-2; STEM-CELLS; SELF-RENEWAL; EXPRESSION;
   DIFFERENTIATION; MUTATIONS; GENE; TRANSFORMATION; HOMEOSTASIS; BLOOD
AB Unremitting blood cell production throughout the lifetime of an organism is reliant on hematopoietic stem cells (HSCs). A rare and relatively quiescent cell type, HSCs are, on entry into cell cycle fated to self-renew, undergo apoptosis or differentiate to progenitors (HPCs) that eventually yield specific classes of blood cells. Disruption of these HSC fate decisions is considered to be fundamental to the development of leukemia. Much effort has therefore been placed on understanding the molecular pathways that regulate HSC fate decisions and how these processes are undermined in leukemia. Transcription factors have emerged as critical regulators in this respect. Here we review the participation of zinc finger transcription factor GATA-2 in regulating normal hematopoietic stem and progenitor cell functionality, myelodysplasia and myeloid leukemia. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Rodrigues, Neil P.; Wang, Zhengke] Boston Univ, Sch Med, Ctr Biomed Res Excellence COBRE Stem Cell Biol, Roger Williams Med Ctr,NIH, Providence, RI 02908 USA.
   [Rodrigues, Neil P.] Boston Univ, Med Ctr, Dept Dermatol, Boston, MA 02118 USA.
   [Rodrigues, Neil P.] Boston Univ, Sch Med, Ctr Regenerat Med, Boston, MA 02118 USA.
   [Tipping, Alex J.; Enver, Tariq] Stem Cell Lab Univ, Coll London UCL Canc Inst, London WC1E 6BT, England.
RP Rodrigues, NP (reprint author), Boston Univ, Sch Med, Roger Williams Med Ctr, NIH COBRE, Prior Off 121A,825 Chalkstone Ave, Providence, RI 02908 USA.
EM neilr@bu.edu
FU NIH [P20RR018757]; BD Biosciences; UK Medical Research Council; UK
   Leukemia and Lymphoma Research; NIH COBRE at Roger Williams Medical
   Center
FX Work in the authors' laboratories is supported by NIH grant P20RR018757
   (NPR), BD Biosciences (NPR), the UK Medical Research Council (TE) and UK
   Leukemia and Lymphoma Research (TE). Additional support to NPR
   laboratory is provided by the administrative and flow cytometry cores
   within the NIH COBRE at Roger Williams Medical Center.
NR 37
TC 17
Z9 18
U1 2
U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1357-2725
J9 INT J BIOCHEM CELL B
JI Int. J. Biochem. Cell Biol.
PD MAR
PY 2012
VL 44
IS 3
BP 457
EP 460
DI 10.1016/j.biocel.2011.12.004
PG 4
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 913YU
UT WOS:000301914100006
PM 22192845
ER

PT J
AU Fu, D
   Arias, IM
AF Fu, Dong
   Arias, Irwin M.
TI Intracellular trafficking of P-glycoprotein
SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
LA English
DT Article
DE P-glycoprotein; Localization; Trafficking; Recycling; Multidrug
   resistance
ID RESISTANT K562 CELLS; MULTIDRUG-RESISTANCE; PROTEIN; GOLGI; EXPRESSION;
   TRANSPORT; MEMBRANE; CANCER; ACTIN; LOCALIZATION
AB Overexpression of P-glycoprotein (P-gp) is a major cause of multidrug resistance in cancer. P-gp is mainly localized in the plasma membrane and can efflux structurally and chemically unrelated substrates, including anticancer drugs. P-gp is also localized in intracellular compartments, such as endoplasmic reticulum (ER), Golgi, endosomes and lysosomes, and cycles between endosomal compartments and the plasma membrane in a microtubular-actin dependent manner. Intracellular trafficking pathways for P-gp and participation of different Rab proteins depend on cellular polarization and choice of primary culture, cell line or neoplasm. Interruption of P-gp trafficking to the plasma membrane increases intracellular P-gp accumulation and anticancer drug levels, suggesting a potential approach to overcome P-gp-mediated multidrug resistance in cancer. Published by Elsevier Ltd.
C1 [Fu, Dong; Arias, Irwin M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
RP Fu, D (reprint author), NICHD, NIH, Bldg 18T,Room 101,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM fudong@mail.nih.gov
RI Fu, Dong /J-1426-2012
FU Intramural NIH HHS [Z99 HD999999]
NR 43
TC 30
Z9 33
U1 2
U2 11
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1357-2725
J9 INT J BIOCHEM CELL B
JI Int. J. Biochem. Cell Biol.
PD MAR
PY 2012
VL 44
IS 3
BP 461
EP 464
DI 10.1016/j.biocel.2011.12.009
PG 4
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 913YU
UT WOS:000301914100007
PM 22212176
ER

PT J
AU Bray, GA
   Smith, SR
   DeJonge, L
   de Souza, R
   Rood, J
   Champagne, CM
   Laranjo, N
   Carey, V
   Obarzanek, E
   Loria, CM
   Anton, SD
   Ryan, DH
   Greenway, FL
   Williamson, D
   Sacks, FM
AF Bray, G. A.
   Smith, S. R.
   DeJonge, L.
   de Souza, R.
   Rood, J.
   Champagne, C. M.
   Laranjo, N.
   Carey, V.
   Obarzanek, E.
   Loria, C. M.
   Anton, S. D.
   Ryan, D. H.
   Greenway, F. L.
   Williamson, D.
   Sacks, F. M.
TI Effect of diet composition on energy expenditure during weight loss: the
   POUNDS LOST Study
SO INTERNATIONAL JOURNAL OF OBESITY
LA English
DT Article
DE doubly labeled water; resting energy expenditure; ventilated hood; body
   composition; activity energy expenditure (PAEE); physical activity level
   (PAL)
ID LOW-FAT DIET; DOUBLY-LABELED WATER; LOW-CARBOHYDRATE-DIET; BODY-WEIGHT;
   PHYSICAL-ACTIVITY; WHITE WOMEN; RANDOMIZED-TRIAL; OBESE-PATIENTS;
   RISK-FACTORS; HIGH-PROTEIN
AB Background: Weight loss reduces energy expenditure, but the contribution of different macronutrients to this change is unclear. Hypothesis: We tested the hypothesis that macronutrient composition of the diet might affect the partitioning of energy expenditure during weight loss.
   Design: A substudy of 99 participants from the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial had total energy expenditure (TEE) measured by doubly labeled water, and resting energy expenditure (REE) measured by indirect calorimetry at baseline and repeated at 6 months in 89 participants. Participants were randomly assigned to one of four diets with either 15 or 25% protein and 20 or 40% fat.
   Results: TEE and REE were positively correlated with each other and with fat-free mass and body fat, at baseline and 6 months. The average weight loss of 8.1 +/- 0.65 kg (least-square mean +/- s.e.) reduced TEE by 120 +/- 56 kcal per day and REE by 136 +/- 18 kcal per day. A greater weight loss at 6 months was associated with a greater decrease in TEE and REE. Participants eating the high-fat diet (HF) lost significantly more fat-free mass (1.52 +/- 0.55 kg) than the low-fat (LF) diet group (P<0.05). Participants eating the LF diet had significantly higher measures of physical activity than the HF group.
   Conclusion: A greater weight loss was associated with a larger decrease in both TEE and REE. The LF diet was associated with significant changes in fat-free body mass and energy expenditure from physical activity compared with the HF diet. International Journal of Obesity (2012) 36, 448-455; doi:10.1038/ijo.2011.173; published online 27 September 2011
C1 [Bray, G. A.; Smith, S. R.; DeJonge, L.; de Souza, R.; Rood, J.; Champagne, C. M.; Laranjo, N.; Carey, V.; Obarzanek, E.; Loria, C. M.; Anton, S. D.; Ryan, D. H.; Greenway, F. L.; Williamson, D.; Sacks, F. M.] Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA.
   [Bray, G. A.; Smith, S. R.; DeJonge, L.; de Souza, R.; Rood, J.; Champagne, C. M.; Laranjo, N.; Carey, V.; Obarzanek, E.; Loria, C. M.; Anton, S. D.; Ryan, D. H.; Greenway, F. L.; Williamson, D.; Sacks, F. M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
   [Bray, G. A.; Smith, S. R.; DeJonge, L.; de Souza, R.; Rood, J.; Champagne, C. M.; Laranjo, N.; Carey, V.; Obarzanek, E.; Loria, C. M.; Anton, S. D.; Ryan, D. H.; Greenway, F. L.; Williamson, D.; Sacks, F. M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
   [Bray, G. A.; Smith, S. R.; DeJonge, L.; de Souza, R.; Rood, J.; Champagne, C. M.; Laranjo, N.; Carey, V.; Obarzanek, E.; Loria, C. M.; Anton, S. D.; Ryan, D. H.; Greenway, F. L.; Williamson, D.; Sacks, F. M.] NHLBI, Bethesda, MD 20892 USA.
RP Bray, GA (reprint author), Pennington Biomed Res Ctr, 6400 Perkins Rd, Baton Rouge, LA 70808 USA.
EM brayga@pbrc.edu
OI de Souza, Russell/0000-0001-8945-513X
FU National Heart, Lung, and Blood Institute, National Institutes of Health
   [HL-073286]
FX This study was supported by Grant HL-073286 from the National Heart,
   Lung, and Blood Institute, National Institutes of Health. We thank the
   participants in the trial for their dedication and contribution to the
   research. We thank the following research staff members for their
   assistance in conducting the trial: Jungnam Joo, Ph.D and Charlotte A.
   Pratt, Ph.D at the National Heart, Lung, and Blood Institute; Patricia
   Copeland, M.S., R.D. at the Harvard School of Public Health; Cassandra
   Carrington, Jacqueline Gallagher, Clota Heazel, Megan Reddy, Alison
   Barr, M.S., R.D., Mary Dinehart, M.S., R.D., Marit Pywell, R.D., Dawn
   Quintino, M.S., R.D., Audrey Shweky, M.S., R.D., Benjamin Harshfield and
   Melissa Mcnery-Stonelake at the Brigham and Women's Hospital; Frank L.
   Greenway, M.D., Julia St. Amant, Elizabeth Tucker, Heidi K. Millet,
   Marisa M. Smith. Sara J. Schoen, R.D., L.D.N., Betsy B. Bernhard,
   Courtney Brock, R.D., Laura DeCuir Moran, R.D., Katherine Lastor, R.D.,
   Erma Levy, M.P.H., R.D., Lisa Miller R.D., Gina Pennington R.D., Dana
   Vieselmeyer, M.P.H., R.D., Marlene Afton, Lindsay Coates, Dawn Turner,
   Richard Dale Achord, Bridget Conner, Margaret Graves, Doris Hoffpauir,
   Carla Kimmel, Steve Lee, Kelli Melancon, Sandra Richard, Stacey Roussel,
   Elizabeth Soroe, Denise Stein, Jamie Tuminello, Ray Allen, Eric LeBlanc
   and Connie Murla at the Pennington Biomedical Research Center. We also
   thank the members of the Data and Safety Monitoring Board: Barbara V.
   Howard, Ph.D (Chair), Phyllis E. Bowen, PhD, Daniel W. Jones, MD,
   Michael G. Perri, PhD, David M. Reboussin, PhD and Marcia L. Stefanick,
   PhD.
NR 43
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Z9 15
U1 3
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0307-0565
J9 INT J OBESITY
JI Int. J. Obes.
PD MAR
PY 2012
VL 36
IS 3
BP 448
EP 455
DI 10.1038/ijo.2011.173
PG 8
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 907MH
UT WOS:000301421300018
PM 21946707
ER

PT J
AU Gandhi, RT
   Coombs, RW
   Chan, ES
   Bosch, RJ
   Zheng, L
   Margolis, DM
   Read, S
   Kallungal, B
   Chang, M
   Goecker, EA
   Wiegand, A
   Kearney, M
   Jacobson, JM
   D'Aquila, R
   Lederman, MM
   Mellors, JW
   Eron, JJ
AF Gandhi, Rajesh T.
   Coombs, Robert W.
   Chan, Ellen S.
   Bosch, Ronald J.
   Zheng, Lu
   Margolis, David M.
   Read, Sarah
   Kallungal, Beatrice
   Chang, Ming
   Goecker, Erin A.
   Wiegand, Ann
   Kearney, Mary
   Jacobson, Jeffrey M.
   D'Aquila, Richard
   Lederman, Michael M.
   Mellors, John W.
   Eron, Joseph J.
CA AIDS Clinical Trials Grp ACTG A524
TI No Effect of Raltegravir Intensification on Viral Replication Markers in
   the Blood of HIV-1-Infected Patients Receiving Antiretroviral Therapy
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE HIV-1; HIV-1 DNA; raltegravir; viral replication; reservoirs; 2-LTR
   circles; T-cell activation
ID T-CELL-ACTIVATION; LOW-LEVEL VIREMIA; INFECTED PATIENTS; HIV-1
   INFECTION; SUPPRESSION; CIRCLES; BURDEN; PLASMA; ADULTS; TRIAL
AB Background: Controversy continues regarding the extent of ongoing viral replication in HIV-1-infected patients on effective antiretroviral therapy (ART). Adding an additional potent agent, such as raltegravir, to effective ART in patients with low-level residual viremia may reveal whether there is ongoing HIV-1 replication.
   Methods: We previously reported the outcome of a randomized placebo-controlled study of raltegravir intensification in patients on ART with HIV-1 RNA,50 copies per milliliter that showed no effect on residual viremia measured by single copy assay. We now report the effects of raltegravir intensification in that trial on other potential measures of ongoing HIV-1 replication as follows: 2-LTR HIV-1 circles, total cellular HIV-1 DNA, and T-cell activation.
   Results: Of 50 patients tested, 12 (24%) had 2-LTR circles detected at baseline. Patients who were 2-LTR-positive had higher plasma HIV-1 RNA and HIV-1 DNA levels than 2-LTR-negative individuals. At week 12 of raltegravir intensification, there was no change from baseline in 2-LTR circles, in total HIV-1 DNA or in the ratio of 2-LTR circles to total HIV-1 DNA. There was also no change in markers of T-cell activation.
   Conclusions: In HIV-1-infected individuals on effective ART, we find no evidence of ongoing viral replication in the blood that is suppressible by raltegravir intensification. The results imply that raltegravir intensification alone will not eradicate HIV-1 infection.
C1 [Gandhi, Rajesh T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
   [Gandhi, Rajesh T.] Massachusetts Gen Hosp, Ragon Inst, Boston, MA 02114 USA.
   [Coombs, Robert W.; Chang, Ming; Goecker, Erin A.] Univ Washington, Sch Med, Dept Lab Med, Div Virol, Seattle, WA 98195 USA.
   [Coombs, Robert W.] Univ Washington, Sch Med, Dept Med, Div Allergy & Infect Dis, Seattle, WA 98195 USA.
   [Chan, Ellen S.; Bosch, Ronald J.; Zheng, Lu; Eron, Joseph J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
   [Margolis, David M.] Univ N Carolina, Ctr Infect Dis, Chapel Hill, NC USA.
   [Read, Sarah] NIAID, HIV Res Branch, Bethesda, MD 20892 USA.
   [Kallungal, Beatrice] Social & Sci Syst Inc, ACTG Operat Ctr, Silver Spring, MD USA.
   [Wiegand, Ann; Kearney, Mary] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA.
   [Jacobson, Jeffrey M.] Drexel Univ, Div Infect Dis & HIV Med, Philadelphia, PA 19104 USA.
   [D'Aquila, Richard] Vanderbilt Univ, Sch Med, Div Infect Dis, Nashville, TN 37212 USA.
   [Lederman, Michael M.] Case Western Reserve Univ, Div Infect Dis & HIV Med, Cleveland, OH 44106 USA.
   [Mellors, John W.] Univ Pittsburgh, Div Infect Dis, Pittsburgh, PA USA.
RP Gandhi, RT (reprint author), Massachusetts Gen Hosp, Div Infect Dis, GRJ 504,55 Fruit St, Boston, MA 02114 USA.
EM rgandhi@partners.org
OI Margolis, David/0000-0001-5714-0002
FU National Institute of Allergy and Infectious Diseases [U01AI068636, AI
   068634]; Virology Support Laboratory of the AIDS Clinical Trials Group
   Central Group [204VC009, 1U01AI068636]; National Cancer
   Institute/Science Applications International Corporation [25XS119];
   National Institute of Health [R01 AI066992-04A1, G08LM008830-01, U01 AI
   694722]; Harvard University Center for AIDS Research (National Institute
   of Health) [2P30 AI060354-06]; University of Washington Center for AIDS
   Research [P30-AI-27757]; AIDS Clinical Trials Group Virology Specialty
   Laboratory [AI-38858]; Roche Molecular Systems; Merck Sharp and Dohme,
   Corp.; Tibotec; Gilead; Merck; Bristol-Myers Squibb;
   GlaxoSmithKline/Viiv; Virco; San Francisco General Hospital CTU [5UO1
   AI069502-03]; MetroHealth CTU [AI 069501]; BSN-University of North
   Carolina AIDS Clinical Trials Unit CTU [AI69423-03]; CFAR [AI50410];
   CTSA [RR025747]; Alabama Therapeutics CRS CTU [U01 AI069452]; GCRC [M01
   RR-00032, RR025780, 5-MO1 RR00044]; Yandow, RN, BSN-Harvard
   Massachusetts General Hospital CTU [1U01AI069472]; PA-C-Stanford
   University CTU [AI069556]; RN-University of Pittsburgh CTU [AI
   069494-01]; BSN-Washington University in St. Louis CTU [AI069495];
   RN-Northwestern University CTU [AI069471]; HIV Prevention and Treatment
   CRS; NYC HHC at Bellevue Hospital Center [AI069532, AI-27665];
   University of Washington, Seattle CTU [AI069434]; Cornell CTU
   [AI069419]; Beth Israel Deaconess (Partners/Harvard) CTU [U01
   AI069472-04]; Harbor UCLA Medical Center CTU [AI069424]; Colorado ACTU
   CTU [AI069450]; University of Rochester CTU [AI69511-02]; Duke
   University Medical Center CTU [5U01 AI069484]; Harlem Family Health
   Center CTU [AI069470];  [AI-68636]
FX Supported by Award Number U01AI068636 from the National Institute of
   Allergy and Infectious Diseases. The project was also supported by a
   grant from the National Institute of Allergy and Infectious Diseases to
   the Statistical and Data Analysis Center (AI 068634). In addition,
   J.W.M. was supported by Virology Support Laboratory subcontract
   (204VC009) of the AIDS Clinical Trials Group Central Group Grant
   (1U01AI068636) and by National Cancer Institute/Science Applications
   International Corporation Contract 25XS119. R.T.G. is supported by
   National Institute of Health R01 AI066992-04A1 and National Institute of
   Health G08LM008830-01 and by grants to the AIDS Clinical Trials Group
   (National Institute of Health U01 AI 694722) and the Harvard University
   Center for AIDS Research (National Institute of Health 2P30
   AI060354-06). The Case Western Reserve Immunology Specialty Laboratory
   is supported by grant AI-68636. R.W.C. received support from the
   University of Washington Center for AIDS Research (P30-AI-27757) and the
   AIDS Clinical Trials Group Virology Specialty Laboratory (AI-38858).
   R.W.C. has received grant support from Roche Molecular Systems and
   served as a consultant to Abbott Laboratories. The study was also
   supported in by a research grant from the Investigator-Initiated Studies
   Program of Merck Sharp and Dohme, Corp.; R.T.G. has received grant
   support from Tibotec and Gilead. D.M.M. has served as a consultant and
   received grant support from Merck, Bristol-Myers Squibb, and Tibotec.
   J.W.M. is a consultant for Gilead Sciences, Merck, and RFS Pharma and
   owns share options in RFS Pharma. M.M.L. has served as a consultant to
   Merck. J.J.E. has served as a consultant and received grant support from
   Merck and GlaxoSmithKline/Viiv and has served as a consultant for
   Bristol-Myers Squibb, Tibotec, Gilead, and Tobira. R.D. has received
   grant support from Merck and Virco and served as a consultant to
   Tibotec.; We would like to thank all the members of the AIDS Clinical
   Trials Group A5244 team, including Randi Leavitt, John Coffin, Sarah
   Palmer, Carla Pettinelli, Ana Martinez, Lisa M. Demeter, Barbara
   Philpotts, Betty A. Donoval, and Robert Levaro. We would like to express
   our special appreciation to Nadia Alatrakchi at Beth Israel Deaconess
   Hospital and Kathy Medvik at Case Western Reserve University for
   performing and analyzing the immunology assays; to Jennifer Janik for
   her excellent work as the study data manager; and to Heather Sprenger
   and Amy Jennings for their outstanding work on coordinating the
   laboratory data for the study. We gratefully acknowledge the hard work
   of the study staff at all the AIDS Clinical Trials Group sites who
   screened and enrolled patients in this trial: Annie Luetkemeyer, MD and
   Joann Volinski, RN-UCSF, San Francisco General Hospital (Site 801) CTU
   Grant # 5UO1 AI069502-03; MetroHealth (Site 2503) CTU Grant # AI 069501;
   David Currin RN and Cheryl Marcus RN, BSN-University of North Carolina
   AIDS Clinical Trials Unit (Site 3201) CTU Grant # AI69423-03, CFAR Grant
   # AI50410, CTSA Grant # RR025747; Melinda Robertson, RN and Rebecca
   Creamer-Alabama Therapeutics CRS (Site 5801) CTU Grant # U01 AI069452,
   GCRC Grant # M01 RR-00032; Amy Sbrolla, RN and Nicole Burgett-Yandow,
   RN, BSN-Harvard Massachusetts General Hospital (Site 101) CTU Grant#
   1U01AI069472; Jane Norris, PA-C and Sandra Valle, PA-C-Stanford
   University (Site 501) CTU Grant # AI069556; Deborah McMahon, MD and
   Sally McNulty, BA, RN-University of Pittsburgh (Site 1001) CTU Grant #
   AI 069494-01; Teresa Spitz, RN, CCRC and Judy Frain, RN, BSN-Washington
   University in St. Louis (Site 2101) CTU Grant # AI069495; Babafemi
   Taiwo, MBBS, MD and Karen Coleman, RN-Northwestern University (Site
   2701) CTU Grant # AI069471; HIV Prevention and Treatment CRS (Site
   30329); Margarita Vasquez, RN and Judith A. Aberg, MD-New York
   University/NYC HHC at Bellevue Hospital Center (Site 401) CTU Grant #
   AI069532, AI-27665; University of Washington, Seattle (Site 1401) CTU
   Grant #AI069434; Todd Stroberg, RN, and Valery Hughes NP-Cornell CTU
   (Site 7804) CTU Grant # AI069419 CTSC# RR024996; Mary Albrecht, MD and
   Amanda Youmans, RN, ANP-Beth Israel Deaconess (Partners/Harvard) (Site
   103) CTU Grant # U01 AI069472-04; Harbor UCLA Medical Center (Site 603)
   CTU Grant #AI069424; M. Graham Ray, RN, MSN and Steven C. Johnson,
   MD-Colorado ACTU (Site 6101) CTU Grant #AI069450 and GCRC Grant #
   RR025780; Amneris Luque MD and Mary Adams, RN-University of Rochester
   (Site 1101) CTU Grant # AI69511-02 (as of 2/12/08), GCRC Grant # 5-MO1
   RR00044; Nathan M. Thielman, MD and Martha Silberman, RN-Duke University
   Medical Center (Site 1601) CTU Grant # 5U01 AI069484; Harlem Family
   Health Center (Site 31483) CTU Grant # AI069470. Finally, we would like
   to thank all the patients who participated in this study
NR 20
TC 54
Z9 54
U1 0
U2 3
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 MAR 1
PY 2012
VL 59
IS 3
BP 229
EP 235
DI 10.1097/QAI.0b013e31823fd1f2
PG 7
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 898UJ
UT WOS:000300767400007
PM 22083073
ER

PT J
AU Cressey, TR
   Stek, A
   Capparelli, E
   Bowonwatanuwong, C
   Prommas, S
   Sirivatanapa, P
   Yuthavisuthi, P
   Neungton, C
   Huo, YL
   Smith, E
   Best, BM
   Mirochnick, M
AF Cressey, Tim R.
   Stek, Alice
   Capparelli, Edmund
   Bowonwatanuwong, Chureeratana
   Prommas, Sinart
   Sirivatanapa, Pannee
   Yuthavisuthi, Prapap
   Neungton, Chanon
   Huo, Yanling
   Smith, Elizabeth
   Best, Brookie M.
   Mirochnick, Mark
CA IMPAACT P1026s Team
TI Efavirenz Pharmacokinetics During the Third Trimester of Pregnancy and
   Postpartum
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article; Proceedings Paper
CT 18th Conference on Retroviruses and Opportunistic Infections (CROI)
CY FEB 27-MAR 02, 2011
CL Boston, MA
DE efavirenz; HIV; pregnancy; pharmacokinetics; prevention of
   mother-to-child transmission of HIV
ID HIV-1-INFECTED WOMEN; NEVIRAPINE; EXPOSURE; PHARMACOGENETICS;
   ANTIRETROVIRALS; METABOLISM; SAFETY; CYP2B6; CHILD
AB Background: The impact of pregnancy on efavirenz (EFV) pharmacokinetics is unknown.
   Methods: International Maternal Pediatric Adolescent AIDS Clinical Trials P1026s is an on-going, prospective, nonblinded study of antiretroviral pharmacokinetics in HIV-infected pregnant women that included a cohort receiving 600 mg EFV once daily as part of combination antiretroviral therapy. Intensive steady-state 24-hour blood sampling was performed during the third trimester and at 6-12 weeks postpartum. Maternal and umbilical cord blood samples were drawn at delivery. Pharmacokinetics targets were the estimated 10th percentile EFV area under the curve (AUC) in nonpregnant historical controls (40.0 mcg . hr(-1) . mL(-1)) and a trough concentration of 1 mcg/mL.
   Results: Twenty-five women were enrolled during the third trimester: median (range) age was 29.3 (18.9-42.9) years, weight 69.0 (40-130) kg, and gestational age 32.9 (30.1-38.7) weeks. Median (range) EFV AUC(0-24), C-max, and C-24 hours were 55.4 mcg . hr(-1) . mL(-1) (13.5-220.3), 5.4 mcg/mL (1.9-12.2), and 1.6 mcg/mL (0.23-8.13), respectively. EFV AUC and C-max did not differ during pregnancy and postpartum but C-24 hours was lower during the third trimester (1.6 vs. 2.1 mcg/mL, P = 0.01). During the third trimester, 5 of 25 (20%) women had an EFV AUC below the target and 3 of 25 (12%) had a trough concentration below 1 mcg/mL. EFV cord blood/maternal concentration ratio was 0.49 (0.37-0.74). All women had a HIV-1 RNA viral load less than 400 copies per milliliter at delivery and 19 (76%) had a viral load below 50 copies per milliliter. One child was perinatally HIV infected. Three women were exposed to EFV throughout the first 6 weeks of pregnancy. EFV was well tolerated, and among the 25 infants, no congenital anomalies or newborn complications were reported.
   Conclusions: Changes in EFV pharmacokinetics during pregnancy compared with postpartum are not sufficiently large enough to warrant a dose adjustment during pregnancy.
C1 [Cressey, Tim R.] Chiang Mai Univ, Fac Associated Med Sci, Dept Med Technol, Program HIV Prevent & Treatment IRD URI 174, Chiang Mai 50000, Thailand.
   [Cressey, Tim R.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
   [Cressey, Tim R.] IRD, UMI 174, Program HIV Prevent & Treatment, Marseille, France.
   [Stek, Alice] Univ So Calif, Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90033 USA.
   [Capparelli, Edmund; Best, Brookie M.] Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA.
   [Capparelli, Edmund; Best, Brookie M.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA 92103 USA.
   [Bowonwatanuwong, Chureeratana] Chonburi Hosp, Dept Internal Med, Chon Buri, Thailand.
   [Prommas, Sinart] Bhumibol Adulyadej Hosp, Dept Obstet & Gynecol, Bangkok, Thailand.
   [Sirivatanapa, Pannee] Chiang Mai Univ, Res Inst Hlth Sci, Chiang Mai 50000, Thailand.
   [Yuthavisuthi, Prapap] Prapokklao Hosp, Dept Obstet & Gynecol, Chanthaburi, Thailand.
   [Neungton, Chanon] Siriraj Hosp, Dept Obstet & Gynecol, Bangkok, Thailand.
   [Huo, Yanling] Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
   [Smith, Elizabeth] NIAID, Bethesda, MD 20892 USA.
   [Mirochnick, Mark] Boston Univ, Sch Med, Boston, MA 02118 USA.
RP Cressey, TR (reprint author), Inst Rech Dev, Program HIV Prevent & Treatment, Dept Med Technol 174, Dept Med Technol,Fac Associated Med Sci, 6th Floor,110 Inthawaroros Rd, Muang Chiang Mai 50200, Thailand.
EM tim@phpt.org
OI Frenkel, Lisa M/0000-0001-9566-8959
FU NIAID NIH HHS [U01 AI068632, AI068632, U01 AI041110, U01 AI041110-09,
   U01 AI068616, U01 AI068616-01, 1 U01 AI068616, 5 U01 AI41110, U01
   AI068632-02, UM1 AI068632, UM1 AI069477]; NICHD NIH HHS
   [HHSN267200800001C]; NIDDK NIH HHS [N01-DK-9-001/HHSN267200800001C,
   HHSN267200800001G]
NR 24
TC 31
Z9 31
U1 0
U2 4
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 MAR 1
PY 2012
VL 59
IS 3
BP 245
EP 252
DI 10.1097/QAI.0b013e31823ff052
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 898UJ
UT WOS:000300767400009
PM 22083071
ER

PT J
AU Wanyama, JN
   Castelnuovo, B
   Robertson, G
   Newell, K
   Sempa, JB
   Kambugu, A
   Manabe, YC
   Colebunders, R
AF Wanyama, Jane N.
   Castelnuovo, Barbara
   Robertson, Gavin
   Newell, Kevin
   Sempa, Joseph B.
   Kambugu, Andrew
   Manabe, Yuka C.
   Colebunders, Robert
TI A Randomized Controlled Trial to Evaluate the Effectiveness of a Board
   Game on Patients' Knowledge Uptake of HIV and Sexually Transmitted
   Diseases at the Infectious Diseases Institute, Kampala, Uganda
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE educational board game; HIV; knowledge uptake; sexually transmitted
   diseases
ID FLOW
AB Background: As the number of HIV infections continues to rise, the search for effective health education strategies must intensify. A new educational board game was developed to increase HIV peoples' attention and knowledge to HIV and sexually transmitted infections (STIs) information. The object of this study was to assess the effect of this educational board game on the uptake of knowledge.
   Methods: A randomized controlled trial where patients attending the Infectious Diseases Clinic, Kampala, Uganda were randomized to either play the board game (intervention arm) or to attend a health talk (standard of care arm). Participants' knowledge was assessed before and after the education sessions through a questionnaire.
   Results: One hundred eighty HIV-positive participants were enrolled, 90 for each study arm. The pretest scores were similar for each arm. There was a statistically significant increase in uptake of knowledge of HIV and STIs in both study arms. Compared with patients in the standard of care arm, participants randomized to the intervention arm had higher uptake of knowledge (4.7 points, 95% confidence interval: 3.9 to 5.4) than the controls (1.5 points, 95% confidence interval: 0.9 to 2.1) with a difference in knowledge uptake between arms of 3.2 points (P < 0.001). Additionally, both participants and facilitators preferred the board game to the health talk as education method.
   Conclusions: The educational game significantly resulted in higher uptake of knowledge of HIV and STIs. Further evaluation of the impact of this educational game on behavioral change in the short and long term is warranted.
C1 [Wanyama, Jane N.; Castelnuovo, Barbara; Sempa, Joseph B.; Kambugu, Andrew; Manabe, Yuka C.] Makerere Univ, Coll Hlth Sci, Infect Dis Inst, Kampala, Uganda.
   [Robertson, Gavin] Univ Witwatersrand, Perinatal HIV Res Unit, Johannesburg, South Africa.
   [Newell, Kevin] SAIC Frederick Inc, NCI Frederick, Clin Monitoring Res Program, Frederick, MD USA.
   [Manabe, Yuka C.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
   [Colebunders, Robert] Inst Trop Med, Dept Clin Sci, B-2000 Antwerp, Belgium.
   [Colebunders, Robert] Univ Antwerp, B-2020 Antwerp, Belgium.
RP Castelnuovo, B (reprint author), Makerere Univ, Infect Dis Inst, Kamala, Uganda.
EM bcastelnuovo@idi.co.ug
OI Bukulu Sempa, Joseph/0000-0003-1062-0417
FU Belgian Technical Cooperation; Flemish Interuniversity Council (VLIR);
   National Cancer Institute, National Institutes of Health
   [HHSN261200800001E]; National Institute of Allergy and Infectious
   Diseases
FX Supported by The Belgian Technical Cooperation and the Flemish
   Interuniversity Council (VLIR).; This project has been funded in whole
   or in part with federal funds from the National Cancer Institute,
   National Institutes of Health, under Contract No. HHSN261200800001E.
   This research was supported in part by the National Institute of Allergy
   and Infectious Diseases.
NR 11
TC 3
Z9 3
U1 0
U2 8
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 MAR 1
PY 2012
VL 59
IS 3
BP 253
EP 258
DI 10.1097/QAI.0b013e31824373d5
PG 6
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 898UJ
UT WOS:000300767400010
PM 22156910
ER

PT J
AU O'Mara, A
   St Germain, D
AF O'Mara, Ann
   St Germain, Diane
TI Improved Outcomes in the Malnourished Patient: We're Not There Yet
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID CANCER; CACHEXIA
C1 [O'Mara, Ann; St Germain, Diane] NCI, Canc Prevent Div, Community Oncol & Prevent Trials Res Grp, NIH, Bethesda, MD 20892 USA.
RP O'Mara, A (reprint author), NCI, Canc Prevent Div, Community Oncol & Prevent Trials Res Grp, NIH, 6130 Execut Blvd,MSC-7340, Bethesda, MD 20892 USA.
EM omaraa@mail.nih.gov
NR 8
TC 1
Z9 1
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 JNCI-J NATL CANCER I
JI J. Natl. Cancer Inst.
PD MAR
PY 2012
VL 104
IS 5
BP 342
EP 343
DI 10.1093/jnci/djs031
PG 2
WC Oncology
SC Oncology
GA 906PH
UT WOS:000301358200001
PM 22345711
ER

PT J
AU Travis, LB
   Ng, AK
   Allan, JM
   Pui, CH
   Kennedy, AR
   Xu, XG
   Purdy, JA
   Applegate, K
   Yahalom, J
   Constine, LS
   Gilbert, ES
   Boice, JD
AF Travis, Lois B.
   Ng, Andrea K.
   Allan, James M.
   Pui, Ching-Hon
   Kennedy, Ann R.
   Xu, X. George
   Purdy, James A.
   Applegate, Kimberly
   Yahalom, Joachim
   Constine, Louis S.
   Gilbert, Ethel S.
   Boice, John D., Jr.
TI Second Malignant Neoplasms and Cardiovascular Disease Following
   Radiotherapy
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID CHILDHOOD-CANCER SURVIVOR; NON-HODGKINS-LYMPHOMA; LONG-TERM SURVIVORS;
   ACUTE LYMPHOBLASTIC-LEUKEMIA; US RADIOLOGIC TECHNOLOGISTS; CONTRALATERAL
   BREAST-CANCER; IONIZING-RADIATION EXPOSURE; ACUTE MYELOID-LEUKEMIA;
   NESTED CASE-CONTROL; DNA-REPAIR GENES
AB Second malignant neoplasms (SMNs) and cardiovascular disease (CVD) are among the most serious and life-threatening late adverse effects experienced by the growing number of cancer survivors worldwide and are due in part to radiotherapy. The National Council on Radiation Protection and Measurements (NCRP) convened an expert scientific committee to critically and comprehensively review associations between radiotherapy and SMNs and CVD, taking into account radiobiology; genomics; treatment (ie, radiotherapy with or without chemotherapy and other therapies); type of radiation; and quantitative considerations (ie, dose-response relationships). Major conclusions of the NCRP include: 1) the relevance of older technologies for current risk assessment when organ-specific absorbed dose and the appropriate relative biological effectiveness are taken into account and 2) the identification of critical research needs with regard to newer radiation modalities, dose-response relationships, and genetic susceptibility. Recommendation for research priorities and infrastructural requirements include 1) long-term large-scale follow-up of extant cancer survivors and prospectively treated patients to characterize risks of SMNs and CVD in terms of radiation dose and type; 2) biological sample collection to integrate epidemiological studies with molecular and genetic evaluations; 3) investigation of interactions between radiotherapy and other potential confounding factors, such as age, sex, race, tobacco and alcohol use, dietary intake, energy balance, and other cofactors, as well as genetic susceptibility; 4) focusing on adolescent and young adult cancer survivors, given the sparse research in this population; and 5) construction of comprehensive risk prediction models for SMNs and CVD to permit the development of follow-up guidelines and prevention and
C1 [Travis, Lois B.; Constine, Louis S.] Univ Rochester, Med Ctr, Rubin Ctr Canc Survivorship, James P Wilmot Canc Ctr, Rochester, NY 14642 USA.
   [Travis, Lois B.; Constine, Louis S.] Univ Rochester, Med Ctr, Dept Radiat Oncol, James P Wilmot Canc Ctr, Rochester, NY 14642 USA.
   [Ng, Andrea K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA.
   [Ng, Andrea K.] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Allan, James M.] Newcastle Univ, No Inst Canc Res, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
   [Pui, Ching-Hon] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA.
   [Pui, Ching-Hon] Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA.
   [Kennedy, Ann R.] Univ Penn, Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA.
   [Xu, X. George] Rensselaer Polytech Inst, Nucl Engn & Engn Phys Program, Troy, NY USA.
   [Purdy, James A.] Univ Calif Davis, Dept Radiat Oncol, Davis, CA 95616 USA.
   [Yahalom, Joachim] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA.
   [Applegate, Kimberly] Emory Univ, Dept Radiol, Atlanta, GA 30322 USA.
   [Gilbert, Ethel S.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Boice, John D., Jr.] Vanderbilt Univ, Dept Med, Nashville, TN USA.
   [Boice, John D., Jr.] Int Epidemiol Inst, Rockville, MD USA.
RP Travis, LB (reprint author), Univ Rochester, Med Ctr, Rubin Ctr Canc Survivorship, James P Wilmot Canc Ctr, 265 Crittenden Blvd,CU 420318, Rochester, NY 14642 USA.
EM Lois_Travis@URMC.Rochester.edu
RI Allan, James/B-4448-2009
FU NCI NIH HHS [CA21765, R24 CA074206]
NR 202
TC 74
Z9 75
U1 3
U2 15
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 JNCI-J NATL CANCER I
JI JNCI-. Natl. Cancer Inst.
PD MAR
PY 2012
VL 104
IS 5
BP 357
EP 370
DI 10.1093/jnci/djr533
PG 14
WC Oncology
SC Oncology
GA 906PH
UT WOS:000301358200009
PM 22312134
ER

PT J
AU Murphy, E
   Patterson, C
AF Murphy, Elizabeth
   Patterson, Cam
TI The expanding world of post-translational modifications
SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
LA English
DT Editorial Material
ID ISCHEMIA/REPERFUSION INJURY; RAT HEART; SYSTEM
C1 [Murphy, Elizabeth] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
   [Patterson, Cam] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA.
RP Murphy, E (reprint author), NHLBI, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM murphy1@nhlbi.nih.gov
FU Intramural NIH HHS [ZIA HL002066-05, ZIA HL006059-03]; NHLBI NIH HHS
   [R37 HL065619]; NIGMS NIH HHS [R01 GM061728]
NR 12
TC 0
Z9 0
U1 0
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2828
EI 1095-8584
J9 J MOL CELL CARDIOL
JI J. Mol. Cell. Cardiol.
PD MAR
PY 2012
VL 52
IS 3
BP 519
EP 519
DI 10.1016/j.yjmcc.2012.01.004
PG 1
WC Cardiac & Cardiovascular Systems; Cell Biology
SC Cardiovascular System & Cardiology; Cell Biology
GA 910EW
UT WOS:000301621000001
PM 22265974
ER

PT J
AU Sack, MN
AF Sack, Michael N.
TI The role of SIRT3 in mitochondrial homeostasis and cardiac adaptation to
   hypertrophy and aging
SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
LA English
DT Review
DE Mitochondria; SIRT3; Cardiac hypertrophy; MnSOD; Cyclophilin D
ID FATTY-ACID OXIDATION; LYSINE ACETYLATION; PERMEABILITY TRANSITION;
   CALORIE RESTRICTION; CELL-DEATH; SIRT3-MEDIATED DEACETYLATION;
   ACETAMINOPHEN HEPATOTOXICITY; SUBCELLULAR COMPARTMENTATION; NAD
   BIOSYNTHESIS; HEART-FAILURE
AB Although acetyl-modification of protein lysine residues has been recognized for many decades, the appreciation that this post-translational modification is highly prevalent in mitochondria and plays a pivotal regulatory role in mitochondrial function has only become apparent since 2006. The classical biological stressors that modulate mitochondrial protein acetylation include alterations in caloric levels and redox signaling and the major enzyme orchestrating deacetylation is the mitochondrial enriched sirtuin SIRT3. Overall the action of SIRT3 modulates mitochondrial homeostasis and SIRT3 target proteins include mediators of energy metabolism and mitochondrial redox stress adaptive program proteins. Given these effects, it is not surprising that the role of SIRT3 has begun to be implicated in cardiac biology. This review gives a brief overview of sirtuin biology and then focuses on the role of the SIRT3 regulatory program in the control of cardiac hypertrophy and aging. This article is part of a Special Section entitled "Post-translational Modification." Published by Elsevier Ltd.
C1 [Sack, Michael N.] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA.
RP Sack, MN (reprint author), Bld 10-CRC,Room 5-3150,10 Ctr Dr,MSC 1454, Bethesda, MD 20892 USA.
EM sackm@nih.gov
FU Division of Intramural Research of the NHLBI; Division of Intramural
   Research of the NHLBI, NIH
FX The Division of Intramural Research of the NHLBI.; MNS is funded by the
   Division of Intramural Research of the NHLBI, NIH.
NR 78
TC 27
Z9 29
U1 1
U2 25
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2828
EI 1095-8584
J9 J MOL CELL CARDIOL
JI J. Mol. Cell. Cardiol.
PD MAR
PY 2012
VL 52
IS 3
BP 520
EP 525
DI 10.1016/j.yjmcc.2011.11.004
PG 6
WC Cardiac & Cardiovascular Systems; Cell Biology
SC Cardiovascular System & Cardiology; Cell Biology
GA 910EW
UT WOS:000301621000002
PM 22119802
ER

PT J
AU Murphy, E
   Kohr, M
   Sun, J
   Nguyen, T
   Steenbergen, C
AF Murphy, Elizabeth
   Kohr, Mark
   Sun, Junhui
   Tiffany Nguyen
   Steenbergen, Charles
TI S-nitrosylation: A radical way to protect the heart
SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
LA English
DT Article
DE Nitric oxide; S-nitrosylation; Ischemia; Cardioprotection; Redox;
   Proteomics
ID NITRIC-OXIDE SYNTHASE; ISCHEMIA-REPERFUSION INJURY; CALCIUM-RELEASE
   CHANNEL; RYANODINE RECEPTOR; ISCHEMIA/REPERFUSION INJURY; VENTRICULAR
   MYOCYTES; GEL-ELECTROPHORESIS; ESTROGEN-RECEPTOR; MASS-SPECTROMETRY;
   CARDIOPROTECTION
AB In this review, the role of S-nitrosylation (SNO) in cardioprotection will be discussed. This review will cover the methodology used to measure SNO levels, and the mechanisms by which SNO serves to modulate cell function and mediate protection. We will also consider whether SNO acts through many targets or whether there are a few key SNO proteins that mediate protection. Issues regarding the percentage of the total protein which is SNO and how this plays a role in the modulation of cell function will also be discussed. The role of nitric oxide synthase uncoupling in cardioprotection will also be addressed. This article is part of a Special Section entitled "Post-translational Modification." Published by Elsevier Ltd.
C1 [Murphy, Elizabeth] NHLBI, Cardiac Physiol Sect, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
   [Kohr, Mark; Steenbergen, Charles] Johns Hopkins Med Ctr, Dept Pathol, Baltimore, MD USA.
RP Murphy, E (reprint author), NHLBI, Cardiac Physiol Sect, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM murphy1@nhlbi.nih.gov
RI Sun, Junhui/C-3499-2011; 
OI Kohr, Mark/0000-0002-6034-5962
FU Intramural NIH HHS [ZIA HL002065-04, ZIA HL002066-04, ZIA HL006059-02];
   NHLBI NIH HHS [R01 HL039752, R01 HL039752-25, F32 HL096142]
NR 94
TC 54
Z9 54
U1 2
U2 11
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2828
EI 1095-8584
J9 J MOL CELL CARDIOL
JI J. Mol. Cell. Cardiol.
PD MAR
PY 2012
VL 52
IS 3
BP 568
EP 577
DI 10.1016/j.yjmcc.2011.08.021
PG 10
WC Cardiac & Cardiovascular Systems; Cell Biology
SC Cardiovascular System & Cardiology; Cell Biology
GA 910EW
UT WOS:000301621000007
PM 21907718
ER

PT J
AU Zhang, K
   Johnson, B
   Gay, M
   Horovitz, SG
   Hallett, M
   Sebastianelli, W
   Slobounov, S
AF Zhang, Kai
   Johnson, Brian
   Gay, Michael
   Horovitz, Silvina G.
   Hallett, Mark
   Sebastianelli, Wayne
   Slobounov, Semyon
TI Default Mode Network in Concussed Individuals in Response to the YMCA
   Physical Stress Test
SO JOURNAL OF NEUROTRAUMA
LA English
DT Article
DE default mode network; resting state functional magnetic resonance
   imaging; subacute phase of mild traumatic brain injury
ID TRAUMATIC BRAIN-INJURY; SPORTS-RELATED CONCUSSION; FUNCTIONAL
   CONNECTIVITY; CORTICAL NETWORKS; STRUCTURAL CONNECTIVITY; PARIETAL
   CORTEX; WORKING-MEMORY; AXONAL INJURY; SHORT-TERM; DYSFUNCTION
AB We hypothesize that the evolution of mild traumatic brain injury (mTBI) may be related to differential effects of a concussive blow on the functional integrity of the brain default mode network (DMN) at rest and/or in response to physical stress. Accordingly, in this resting-state functional magnetic resonance imaging (fMRI) study, we examined 14 subjects 10 +/- 2 days post-sports-related mTBI and 15 age-matched normal volunteers (NVs) to investigate the possibility that the integrity of the DMN is disrupted at the resting state and/or following the physical stress test. First, all mTBI subjects were asymptomatic based upon clinical evaluation and neuropsychological (NP) assessments prior to the MRI session. Second, the functional integrity within the DMN, a main resting-state network, remained resilient to a single concussive blow. Specifically, the major regions of interest (ROIs) constituting the DMN (e. g., the posterior cingulate cortex [PCC]/precuneus area, the medial prefrontal cortex [MPFC], and left and right lateral parietal cortices [LLP and RLP]) and the connectivity within these four ROIs was similar between NVs and mTBI subjects prior to the YMCA physical stress test. However, the YMCA physical stress test disrupted the DMN, significantly reducing the magnitude of the connection between the PCC and left lateral parietal ROI, and PCC and right lateral parietal ROI, as well as between the PCC and MPFC in mTBI subjects. Thus while the DMN remained resilient to a single mTBI without exertion at 10 days post-injury, it was altered in response to limited physical stress. This may explain some clinical features of mTBI and provide some insight into its mechanism. This important finding should be considered by clinical practitioners when making decisions regarding return-to-play and clearing mTBI athletes for sports participation.
C1 [Zhang, Kai; Johnson, Brian; Gay, Michael; Sebastianelli, Wayne; Slobounov, Semyon] Penn State Univ, Dept Kinesiol, University Pk, PA 16802 USA.
   [Horovitz, Silvina G.; Hallett, Mark; Slobounov, Semyon] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
   [Sebastianelli, Wayne; Slobounov, Semyon] Penn State Univ, Dept Orthopaed & Med Rehabil, University Pk, PA 16802 USA.
RP Slobounov, S (reprint author), Penn State Univ, Dept Kinesiol, 19 Recreat Bldg, University Pk, PA 16802 USA.
EM sms18@psu.edu
FU National Institutes of Health [RO1 NS056227-01A2]
FX This work was supported by National Institutes of Health Grant RO1
   NS056227-01A2 "Identification of Athletes at Risk for Traumatic Brain
   Injury'' awarded to Dr. Slobounov, Principal Investigator.
NR 72
TC 27
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U1 1
U2 11
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
J9 J NEUROTRAUM
JI J. Neurotrauma
PD MAR
PY 2012
VL 29
IS 5
BP 756
EP 765
DI 10.1089/neu.2011.2125
PG 10
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA 907TZ
UT WOS:000301442900006
PM 22040294
ER

PT J
AU Wu, LT
   Blazer, DG
   Woody, GE
   Burchett, B
   Yang, CM
   Pan, JJ
   Ling, W
AF Wu, Li-Tzy
   Blazer, Dan G.
   Woody, George E.
   Burchett, Bruce
   Yang, Chongming
   Pan, Jeng-Jong
   Ling, Walter
TI Alcohol and drug dependence symptom items as brief screeners for
   substance use disorders: Results from the Clinical Trials Network
SO JOURNAL OF PSYCHIATRIC RESEARCH
LA English
DT Article
DE Clinical Trials Network; Item response theory; Receiver operating
   characteristic curve; Brief screening; Sensitivity; Specificity;
   Substance use disorders
ID ITEM RESPONSE THEORY; OPIOID USE DISORDERS; PRIMARY-CARE; TREATMENT
   SERVICES; ILLICIT DRUG; ABUSE; INTERVENTIONS; ADOLESCENTS; QUESTIONS;
   HEROIN
AB Aim: To address an urgent need for screening of substance use problems in medical settings, we examined substance-specific dependence criteria as potential brief screeners for the detection of patients with a substance use disorder (SUD).
   Methods: The sample included 920 opioid-dependent adults who were recruited from outpatient treatment settings at 11 programs in 10 U.S. cities and who completed intake assessments of SUDs for a multisite study of the National Drug Abuse Treatment Clinical Trials Network (CTN003). Data were analyzed by factor analysis, item response theory (IRT), sensitivity, and specificity procedures.
   Results: Across all substances (alcohol, amphetamines, cannabis, cocaine, sedatives), withdrawal was among the least prevalent symptoms, while taking large amounts and inability to cut down were among the most prevalent symptoms. Items closely related to the latent trait of a SUD showed good-to-high values of area under the receiver operating characteristic curve in identifying cases of a SUD; IRT-defined severe and less discriminative items exhibited low sensitivity in identifying cases of a SUD (withdrawal for all substances; time using for alcohol and sedatives; giving up activities for sedatives).
   Conclusions: Study results suggest that withdrawal and time using are much less reliable indicators for a SUD than taking larger amounts than intended and inability to cut down and that the latter two items should be studied further for consideration in developing a simplified tool for screening patients for SUDs in medical settings. These findings have implications for the use of common health indicators in electronic health records systems to improve patient care. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Wu, Li-Tzy; Blazer, Dan G.; Burchett, Bruce] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Sch Med, Durham, NC 27710 USA.
   [Woody, George E.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA.
   [Woody, George E.] Treatment Res Inst, Philadelphia, PA USA.
   [Yang, Chongming] Duke Univ, Social Sci Res Inst, Durham, NC 27710 USA.
   [Pan, Jeng-Jong] NCI, NIH, Bethesda, MD 20892 USA.
   [Ling, Walter] Univ Calif Los Angeles, David Geffen Sch Med, NPI Integrated Subst Abuse Programs, Los Angeles, CA 90095 USA.
RP Wu, LT (reprint author), Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Sch Med, Box 3419, Durham, NC 27710 USA.
EM litzy.wu@duke.edu
FU U.S. National Institute on Drug Abuse of the National Institutes of
   Health [R21DA027503, R33DA027503, R01DA019623, R01DA019901, WO DA013045,
   HSN271200522071C, K05DA017009, U10DA013043]
FX This work was made possible by research grants from the U.S. National
   Institute on Drug Abuse of the National Institutes of Health:
   R21DA027503, R33DA027503, R01DA019623, and R01DA019901 (PI: Li-Tzy Wu);
   WO DA013045 (PI: Walter Ling); HSN271200522071C (PI: Dan G. Blazer);
   K05DA017009 and U10DA013043 (PI: George E. Woody). The sponsoring agency
   had no further role in the study design and analysis, the writing of the
   report, or the decision to submit the paper for publication. The
   opinions expressed in this paper are solely those of the authors.
NR 45
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Z9 8
U1 1
U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0022-3956
J9 J PSYCHIATR RES
JI J. Psychiatr. Res.
PD MAR
PY 2012
VL 46
IS 3
BP 360
EP 369
DI 10.1016/j.jpsychires.2011.12.002
PG 10
WC Psychiatry
SC Psychiatry
GA 911YJ
UT WOS:000301760300013
PM 22204775
ER

PT J
AU Zhou, DW
   Chung, SH
   Miller, M
   Le Grice, SFJ
   Wlodawer, A
AF Zhou, Dongwen
   Chung, Suhman
   Miller, Maria
   Le Grice, Stuart F. J.
   Wlodawer, Alexander
TI Crystal structures of the reverse transcriptase-associated ribonuclease
   H domain of xenotropic murine leukemia-virus related virus
SO JOURNAL OF STRUCTURAL BIOLOGY
LA English
DT Article
DE XMRV; Retrovirus; RNase H; Crystal structure; Enzyme inhibition
ID CHRONIC-FATIGUE-SYNDROME; RNASE-H; ESCHERICHIA-COLI; INFECTIOUS
   RETROVIRUS; DIFFRACTION DATA; RNA/DNA HYBRID; ACTIVE-SITE; BLOOD-CELLS;
   XMRV; SPECIFICITY
AB The ribonuclease H (RNase H) domain of retroviral reverse transcriptase (RT) plays a critical role in the life cycle by degrading the RNA strands of DNA/RNA hybrids. In addition, RNase H activity is required to precisely remove the RNA primers from nascent (-) and (+) strand DNA. We report here three crystal structures of the RNase H domain of xenotropic murine leukemia virus-related virus (XMRV) RI. namely (i) the previously identified construct from which helix C was deleted, (ii) the intact domain, and (iii) the intact domain complexed with an active site alpha-hydroxytropolone inhibitor. Enzymatic assays showed that the intact RNase H domain retained catalytic activity, whereas the variant lacking helix C was only marginally active, corroborating the importance of this helix for enzymatic activity. Modeling of the enzyme-substrate complex elucidated the essential role of helix C in binding a DNA/RNA hybrid and its likely mode of recognition. The crystal structure of the RNase H domain complexed with beta-thujaplicinol clearly showed that coordination by two divalent cations mediates recognition of the inhibitor. Published by Elsevier Inc.
C1 [Zhou, Dongwen; Miller, Maria; Wlodawer, Alexander] NCI, Prot Struct Sect, MCL, Frederick, MD 21702 USA.
   [Chung, Suhman; Le Grice, Stuart F. J.] NCI, RT Biochem Sect, Retroviral Replicat Lab, HIV Drug Resistance Program, Frederick, MD 21702 USA.
RP Wlodawer, A (reprint author), NCI, Prot Struct Sect, MCL, Bldg 536,Rm 5, Frederick, MD 21702 USA.
EM wlodawer@nih.gov
RI Miller, Maria/I-1636-2013
OI Miller, Maria/0000-0003-0252-5348
FU NIH; National Cancer Institute; Center for Cancer Research
FX We thank Dr. Zbyszek Dauter and Mi Li for help with data processing, and
   Dr. Genbin Shi for help with structure modeling. This project was
   supported by the Intramural Research Program of the NIH, National Cancer
   Institute, Center for Cancer Research.
NR 28
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Z9 7
U1 0
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1047-8477
J9 J STRUCT BIOL
JI J. Struct. Biol.
PD MAR
PY 2012
VL 177
IS 3
BP 638
EP 645
DI 10.1016/j.jsb.2012.02.006
PG 8
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 913RK
UT WOS:000301894900006
PM 22366278
ER

PT J
AU Perera, PY
   Lichy, JH
   Waldmann, TA
   Perera, LP
AF Perera, Pin-Yu
   Lichy, Jack H.
   Waldmann, Thomas A.
   Perera, Liyanage P.
TI The role of interleukin-15 in inflammation and immune responses to
   infection: implications for its therapeutic use
SO MICROBES AND INFECTION
LA English
DT Review
DE IL-15; Infectious diseases; Vaccines; Inflammation; Molecular adjuvants
ID NATURAL-KILLER-CELLS; CD8(+) T-CELLS; HERPES-SIMPLEX-VIRUS; FOLLICULAR
   DENDRITIC CELLS; IL-15 TRANSGENIC MICE; RECEPTOR-ALPHA-CHAIN;
   EPSTEIN-BARR-VIRUS; NK CELLS; HIV-INFECTION; HEPATITIS-B
AB Interleukin-15 (IL-15) is a pleiotropic cytokine with a broad range of biological functions in many diverse cell types. It plays a major role in the development of inflammatory and protective immune responses to microbial invaders and parasites by modulating immune cells of both the innate and adaptive immune systems. This review provides an overview of the mechanisms by which IL-15 modulates the host response to infectious agents and its utility as a cytokine adjuvant in vaccines against infectious pathogens. Published by Elsevier Masson SAS on behalf of Institut Pasteur.
C1 [Waldmann, Thomas A.; Perera, Liyanage P.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Perera, Pin-Yu; Lichy, Jack H.] Vet Affairs Med Ctr, Washington, DC 20422 USA.
RP Perera, LP (reprint author), NCI, Metab Branch, Ctr Canc Res, NIH, Bldg 10,Rm 4N114, Bethesda, MD 20892 USA.
EM pereral@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 138
TC 27
Z9 31
U1 1
U2 11
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1286-4579
J9 MICROBES INFECT
JI Microbes Infect.
PD MAR
PY 2012
VL 14
IS 3
BP 247
EP 261
DI 10.1016/j.micinf.2011.10.006
PG 15
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 911EW
UT WOS:000301701100005
PM 22064066
ER

PT J
AU Craig, K
   Young, MJ
   Blakely, EL
   Longley, MJ
   Turnbull, DM
   Copeland, WC
   Taylor, RW
AF Craig, Kate
   Young, Matthew J.
   Blakely, Emma L.
   Longley, Matthew J.
   Turnbull, Douglass M.
   Copeland, William C.
   Taylor, Robert W.
TI A p.R369G POLG2 mutation associated with adPEO and multiple mtDNA
   deletions causes decreased affinity between polymerase gamma subunits
SO MITOCHONDRION
LA English
DT Article
DE Mitochondrial DNA polymerase; POLG2; adPEO; Multiple mtDNA deletions;
   Recombinant enzyme; Replication stalling
ID MITOCHONDRIAL-DNA DELETIONS; PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA;
   REAL-TIME PCR; INDIVIDUAL CELLS; OPTIC ATROPHY; DISEASE; DISORDER;
   MAINTENANCE; MYOPATHY; PATIENT
AB Human mitochondrial DNA (mtDNA) polymerase gamma (pol gamma) is the sole enzyme required to replicate and maintain the integrity of the mitochondrial genome. It comprises two subunits, a catalytic p140 subunit and a smaller p55 accessory subunit encoded by the POLG2 gene. We describe the molecular characterization of a potential dominant POLG2 mutation (p.R369G) in a patient with adPEO and multiple mtDNA deletions. Biochemical studies of the recombinant mutant p55 protein showed a reduced affinity to the pol gamma p140 subunit, leading to impaired processivity of the holoenzyme complex but did not show sensitivity to N-ethylmalaimide (NEM) inhibition, inferring a novel disease mechanism. (C) 2011 Elsevier B.V. and Mitochondria Research Society. All rights reserved.
C1 [Craig, Kate; Blakely, Emma L.; Turnbull, Douglass M.; Taylor, Robert W.] Newcastle Univ, Sch Med, Inst Ageing & Hlth, Mitochondrial Res Grp, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
   [Young, Matthew J.; Longley, Matthew J.; Copeland, William C.] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Taylor, RW (reprint author), Newcastle Univ, Sch Med, Inst Ageing & Hlth, Mitochondrial Res Grp, Framlington Pl, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
EM robert.taylor@ncl.ac.uk
FU Wellcome Trust [074454/Z/04/Z]; UK NHS; NIH, National Institute of
   Environmental Health Sciences [ES 065078]
FX This work was supported by a Wellcome Trust Programme Grant
   [074454/Z/04/Z], the UK NHS Specialist Commissioners which funds the
   "Rare Mitochondrial Disorders of Adults and Children" Diagnostic Service
   in Newcastle upon Tyne (http://www.mitochondrialncg.nhs.uk) and by the
   Intramural Research Program of the NIH, National Institute of
   Environmental Health Sciences [ES 065078].
NR 26
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U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1567-7249
J9 MITOCHONDRION
JI Mitochondrion
PD MAR
PY 2012
VL 12
IS 2
BP 313
EP 319
DI 10.1016/j.mito.2011.11.006
PG 7
WC Cell Biology; Genetics & Heredity
SC Cell Biology; Genetics & Heredity
GA 913VX
UT WOS:000301906600018
PM 22155748
ER

PT J
AU Kedar, PS
   Stefanick, DF
   Horton, JK
   Wilson, SH
AF Kedar, Padmini S.
   Stefanick, Donna F.
   Horton, Julie K.
   Wilson, Samuel H.
TI Increased PARP-1 Association with DNA in Alkylation Damaged,
   PARP-Inhibited Mouse Fibroblasts
SO MOLECULAR CANCER RESEARCH
LA English
DT Article
ID BASE-EXCISION-REPAIR; STRAND BREAK REPAIR; POLY(ADP-RIBOSE)
   POLYMERASE-ACTIVITY; CELL-DEATH; MAMMALIAN-CELLS; CANCER-THERAPY; HUMAN
   GENOME; ISOCHORES; BETA; IDENTIFICATION
AB Treatment of base excision repair-proficient mouse fibroblasts with the DNA alkylating agent methyl methanesulfonate (MMS) and a small molecule inhibitor of PARP-1 results in a striking cell killing phenotype, as previously reported. Earlier studies showed that the mechanism of cell death is apoptosis and requires DNA replication, expression of PARP-1, and an intact S-phase checkpoint cell signaling system. It is proposed that activity-inhibited PARP-1 becomes immobilized at DNA repair intermediates, and that this blocks DNA repair and interferes with DNA replication, eventually promoting an S-phase checkpoint and G(2)-M block. Here we report studies designed to evaluate the prediction that inhibited PARP-1 remains DNA associated in cells undergoing repair of alkylation-induced damage. Using chromatin immunoprecipitation with anti-PARP-1 antibody and qPCR for DNA quantification, a higher level of DNA was found associated with PARP-1 in cells treated with MMS plus PARP inhibitor than in cells without inhibitor treatment. These results have implications for explaining the extreme hypersensitivity phenotype after combination treatment with MMS and a PARP inhibitor. Mol Cancer Res; 10(3); 360-8. (C)2012 AACR.
C1 [Kedar, Padmini S.; Stefanick, Donna F.; Horton, Julie K.; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM wilson5@niehs.nih.gov
FU NIH, National Institute of Environmental Health Sciences [Z01-ES050159]
FX This research was supported by Research Project Number Z01-ES050159 in
   the Intramural Research Program of the NIH, National Institute of
   Environmental Health Sciences.
NR 42
TC 23
Z9 23
U1 0
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1541-7786
J9 MOL CANCER RES
JI Mol. Cancer Res.
PD MAR
PY 2012
VL 10
IS 3
BP 360
EP 368
DI 10.1158/1541-7786.MCR-11-0477
PG 9
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 912EO
UT WOS:000301777700009
PM 22246237
ER

PT J
AU du Souich, C
   McLarren, K
   Nowaczyk, MJM
   Whitman, JC
   Livesley, J
   Woodward, TS
   Steiner, RD
   Boerkoel, CF
AF du Souich, Christele
   McLarren, Keith
   Nowaczyk, M. J. M.
   Whitman, J. C.
   Livesley, J.
   Woodward, T. S.
   Steiner, R. D.
   Boerkoel, Cornelius F.
TI CK syndrome: another glimpse of neurodevelopmental regulation by
   cholesterol biosynthesis
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 35th Annual Meeting of the Society-for-Inherited-Metabolic-Disorders
   (SIMD)
CY MAR 31-APR 03, 2012
CL Charlotte, NC
SP Soc Inherited Metabol Disorders (SIMD), Abbott Nutr (Abbott Metabol), Pfizer Inc, Shire, Actel Pharmaceut (ACTELION), Cytonet LLC, GeneDx, Genzyme, Hyper Therapeut, Inc, Mead Johnson Nutr, Orphan Europe Recordati Grp, Rare Dis Therapeut, Inc, Ucyclyd Pharma, Vitaflo, Appl Nutr Corp, ARUP Labs, BioMarin Pharmaceut, Inc, Cambrooke Foods, Inc, Emory Genet Lab, Hitachi High Technol Amer, Inc, Prevent Genet, Transgenom, Inc, Canadian PKU & Allied Disorders Inc, Natl PKU Alliance, Natl Urea Cycle Disorders Fdn, Propion Acidemia Fdn, United Mitochondrial Dis Fdn
C1 [du Souich, Christele; McLarren, Keith; Boerkoel, Cornelius F.] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada.
   [du Souich, Christele; McLarren, Keith; Boerkoel, Cornelius F.] Univ British Columbia, Child & Family Res Inst, Vancouver, BC V5Z 1M9, Canada.
   [Nowaczyk, M. J. M.] McMaster Univ, Dept Pathol & Mol Med & Pediat, Hamilton, ON L8S 4L8, Canada.
   [Whitman, J. C.; Livesley, J.; Woodward, T. S.] Univ British Columbia, Dept Psychiat, Vancouver, BC, Canada.
   [Steiner, R. D.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
   [Boerkoel, Cornelius F.] NIH, Undiagnosed Dis Program, Bethesda, MD 20892 USA.
   [Boerkoel, Cornelius F.] NHGRI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD MAR
PY 2012
VL 105
IS 3
BP 281
EP 282
PG 2
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
   Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
   Medicine
GA 913VV
UT WOS:000301906400003
ER

PT J
AU Porter, FD
AF Porter, Forbes D.
CA NIH TRND Team
TI Development of therapeutic interventions for Niemann-Pick disease, type
   C1
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 35th Annual Meeting of the Society-for-Inherited-Metabolic-Disorders
   (SIMD)
CY MAR 31-APR 03, 2012
CL Charlotte, NC
SP Soc Inherited Metabol Disorders (SIMD), Abbott Nutr (Abbott Metabol), Pfizer Inc, Shire, Actel Pharmaceut (ACTELION), Cytonet LLC, GeneDx, Genzyme, Hyper Therapeut, Inc, Mead Johnson Nutr, Orphan Europe Recordati Grp, Rare Dis Therapeut, Inc, Ucyclyd Pharma, Vitaflo, Appl Nutr Corp, ARUP Labs, BioMarin Pharmaceut, Inc, Cambrooke Foods, Inc, Emory Genet Lab, Hitachi High Technol Amer, Inc, Prevent Genet, Transgenom, Inc, Canadian PKU & Allied Disorders Inc, Natl PKU Alliance, Natl Urea Cycle Disorders Fdn, Propion Acidemia Fdn, United Mitochondrial Dis Fdn
C1 [Porter, Forbes D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, DHHS, Bethesda, MD USA.
   [NIH TRND Team] NIH, Therapeut Rare & Neglected Dis Program, DHHS, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD MAR
PY 2012
VL 105
IS 3
BP 286
EP 286
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
   Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
   Medicine
GA 913VV
UT WOS:000301906400015
ER

PT J
AU Southall, NT
   McKew, J
AF Southall, Noel T.
   McKew, John
TI NIH Therapeutics for Rare and Neglected Diseases (TRND) program
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 35th Annual Meeting of the Society-for-Inherited-Metabolic-Disorders
   (SIMD)
CY MAR 31-APR 03, 2012
CL Charlotte, NC
SP Soc Inherited Metabol Disorders (SIMD), Abbott Nutr (Abbott Metabol), Pfizer Inc, Shire, Actel Pharmaceut (ACTELION), Cytonet LLC, GeneDx, Genzyme, Hyper Therapeut, Inc, Mead Johnson Nutr, Orphan Europe Recordati Grp, Rare Dis Therapeut, Inc, Ucyclyd Pharma, Vitaflo, Appl Nutr Corp, ARUP Labs, BioMarin Pharmaceut, Inc, Cambrooke Foods, Inc, Emory Genet Lab, Hitachi High Technol Amer, Inc, Prevent Genet, Transgenom, Inc, Canadian PKU & Allied Disorders Inc, Natl PKU Alliance, Natl Urea Cycle Disorders Fdn, Propion Acidemia Fdn, United Mitochondrial Dis Fdn
C1 [Southall, Noel T.; McKew, John] NIH, NIH Ctr Translat Therapeut, 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 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD MAR
PY 2012
VL 105
IS 3
BP 287
EP 288
PG 2
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
   Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
   Medicine
GA 913VV
UT WOS:000301906400019
ER

PT J
AU Wolfe, L
AF Wolfe, Lynne
TI New disorders of dolichol metabolism
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 35th Annual Meeting of the Society-for-Inherited-Metabolic-Disorders
   (SIMD)
CY MAR 31-APR 03, 2012
CL Charlotte, NC
SP Soc Inherited Metabol Disorders (SIMD), Abbott Nutr (Abbott Metabol), Pfizer Inc, Shire, Actel Pharmaceut (ACTELION), Cytonet LLC, GeneDx, Genzyme, Hyper Therapeut, Inc, Mead Johnson Nutr, Orphan Europe Recordati Grp, Rare Dis Therapeut, Inc, Ucyclyd Pharma, Vitaflo, Appl Nutr Corp, ARUP Labs, BioMarin Pharmaceut, Inc, Cambrooke Foods, Inc, Emory Genet Lab, Hitachi High Technol Amer, Inc, Prevent Genet, Transgenom, Inc, Canadian PKU & Allied Disorders Inc, Natl PKU Alliance, Natl Urea Cycle Disorders Fdn, Propion Acidemia Fdn, United Mitochondrial Dis Fdn
C1 [Wolfe, Lynne] NHGRI, NIH, Undiag Dis Program, Bethesda, MD USA.
NR 3
TC 0
Z9 0
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 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD MAR
PY 2012
VL 105
IS 3
BP 288
EP 288
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
   Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
   Medicine
GA 913VV
UT WOS:000301906400021
ER

PT J
AU Kruszka, PS
   Manoli, I
   Sloan, J
   Venditti, CP
AF Kruszka, Paul S.
   Manoli, Irini
   Sloan, Jennifer
   Venditti, Charles P.
TI Kidney growth in methylmalonic acidemia (MMA)
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 35th Annual Meeting of the Society-for-Inherited-Metabolic-Disorders
   (SIMD)
CY MAR 31-APR 03, 2012
CL Charlotte, NC
SP Soc Inherited Metabol Disorders (SIMD), Abbott Nutr (Abbott Metabol), Pfizer Inc, Shire, Actel Pharmaceut (ACTELION), Cytonet LLC, GeneDx, Genzyme, Hyper Therapeut, Inc, Mead Johnson Nutr, Orphan Europe Recordati Grp, Rare Dis Therapeut, Inc, Ucyclyd Pharma, Vitaflo, Appl Nutr Corp, ARUP Labs, BioMarin Pharmaceut, Inc, Cambrooke Foods, Inc, Emory Genet Lab, Hitachi High Technol Amer, Inc, Prevent Genet, Transgenom, Inc, Canadian PKU & Allied Disorders Inc, Natl PKU Alliance, Natl Urea Cycle Disorders Fdn, Propion Acidemia Fdn, United Mitochondrial Dis Fdn
C1 [Kruszka, Paul S.; Manoli, Irini; Sloan, Jennifer; Venditti, Charles P.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
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 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD MAR
PY 2012
VL 105
IS 3
BP 292
EP 292
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
   Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
   Medicine
GA 913VV
UT WOS:000301906400026
ER

PT J
AU Yardeni, T
   Niethamer, TK
   Jay, CM
   Leoyklang, P
   Jacobs, K
   Anikster, Y
   Ciccone, C
   Maples, PB
   Nemunaitis, J
   Hoogstraten-Miller, SL
   Gahl, WA
   Huizing, M
AF Yardeni, T.
   Niethamer, T. K.
   Jay, C. M.
   Leoyklang, P.
   Jacobs, K.
   Anikster, Y.
   Ciccone, C.
   Maples, P. B.
   Nemunaitis, J.
   Hoogstraten-Miller, S. L.
   Gahl, W. A.
   Huizing, M.
TI Utilizing liposomes for successful systemic delivery of monosaccharides
   for metabolic disorders
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 35th Annual Meeting of the Society-for-Inherited-Metabolic-Disorders
   (SIMD)
CY MAR 31-APR 03, 2012
CL Charlotte, NC
SP Soc Inherited Metabol Disorders (SIMD), Abbott Nutr (Abbott Metabol), Pfizer Inc, Shire, Actel Pharmaceut (ACTELION), Cytonet LLC, GeneDx, Genzyme, Hyper Therapeut, Inc, Mead Johnson Nutr, Orphan Europe Recordati Grp, Rare Dis Therapeut, Inc, Ucyclyd Pharma, Vitaflo, Appl Nutr Corp, ARUP Labs, BioMarin Pharmaceut, Inc, Cambrooke Foods, Inc, Emory Genet Lab, Hitachi High Technol Amer, Inc, Prevent Genet, Transgenom, Inc, Canadian PKU & Allied Disorders Inc, Natl PKU Alliance, Natl Urea Cycle Disorders Fdn, Propion Acidemia Fdn, United Mitochondrial Dis Fdn
C1 [Yardeni, T.; Niethamer, T. K.; Leoyklang, P.; Jacobs, K.; Ciccone, C.; Hoogstraten-Miller, S. L.; Gahl, W. A.; Huizing, M.] NHGRI, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
   [Yardeni, T.; Anikster, Y.] Tel Aviv Univ, Sheba Med Ctr, IL-69978 Tel Aviv, Israel.
   [Yardeni, T.; Anikster, Y.] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel.
   [Jay, C. M.; Maples, P. B.; Nemunaitis, J.] Gradalis Inc, Dallas, TX USA.
   [Gahl, W. A.] NIH, Intramural Res Program, Off Director, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
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 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD MAR
PY 2012
VL 105
IS 3
BP 296
EP 296
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
   Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
   Medicine
GA 913VV
UT WOS:000301906400033
ER

PT J
AU Baric, I
   Cuk, M
   Petkovic-Ramadza, D
   Bilic, K
   Zibar, K
   Sarnavka, V
   Vugrek, O
   Burlina, A
   Mudd, SH
   Fumic, K
AF Baric, Ivo
   Cuk, Mario
   Petkovic-Ramadza, Danijela
   Bilic, Karmen
   Zibar, Karin
   Sarnavka, Vladimir
   Vugrek, Oliver
   Burlina, Alberto
   Mudd, S. Harvey
   Fumic, Ksenija
TI S-Adenosylhomocysteine hydrolase deficiency - a review of nine patients
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 35th Annual Meeting of the Society-for-Inherited-Metabolic-Disorders
   (SIMD)
CY MAR 31-APR 03, 2012
CL Charlotte, NC
SP Soc Inherited Metabol Disorders (SIMD), Abbott Nutr (Abbott Metabol), Pfizer Inc, Shire, Actel Pharmaceut (ACTELION), Cytonet LLC, GeneDx, Genzyme, Hyper Therapeut, Inc, Mead Johnson Nutr, Orphan Europe Recordati Grp, Rare Dis Therapeut, Inc, Ucyclyd Pharma, Vitaflo, Appl Nutr Corp, ARUP Labs, BioMarin Pharmaceut, Inc, Cambrooke Foods, Inc, Emory Genet Lab, Hitachi High Technol Amer, Inc, Prevent Genet, Transgenom, Inc, Canadian PKU & Allied Disorders Inc, Natl PKU Alliance, Natl Urea Cycle Disorders Fdn, Propion Acidemia Fdn, United Mitochondrial Dis Fdn
C1 [Baric, Ivo; Cuk, Mario; Petkovic-Ramadza, Danijela; Sarnavka, Vladimir] Univ Hosp Ctr, Dept Pediat, Zagreb, Croatia.
   [Bilic, Karmen; Fumic, Ksenija] Univ Hosp Ctr, Clin Inst Lab Diag, Zagreb, Croatia.
   [Baric, Ivo; Cuk, Mario; Zibar, Karin] Univ Zagreb, Sch Med, Zagreb 41000, Croatia.
   [Vugrek, Oliver] Rudjer Boskovic Inst, Zagreb, Croatia.
   [Burlina, Alberto] Univ Padua, Dept Pediat, Padua, Italy.
   [Mudd, S. Harvey] NIMH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD MAR
PY 2012
VL 105
IS 3
BP 303
EP 303
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
   Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
   Medicine
GA 913VV
UT WOS:000301906400042
ER

EF