FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Tong, ZB
Tu, W
Wei, QX
DeCherney, AH
Nelson, LM
AF Tong, Zhi-Bin
Tu, Wei
Wei, Qingxiang
DeCherney, Alan H.
Nelson, Lawrence M.
TI P450-Side Chain Cleavage Enzyme Is an Ovarian Antigen in Murine
Experimental Autoimmune Oophoritis.
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010)
CY JUN 19-22, 2010
CL San Diego, CA
SP Endocrine Society
C1 [Tong, Zhi-Bin; Tu, Wei; Wei, Qingxiang; DeCherney, Alan H.; Nelson, Lawrence M.] NICHD, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0163-769X
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2010
VL 31
IS 3
SU 1
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 652FV
UT WOS:000281989402379
ER
PT J
AU Tsang, K
Starost, MF
Nesterova, M
Boikos, SA
Watkins, T
Almeida, MQ
Harran, M
Li, A
Collins, MT
Cheadle, C
Mertz, EL
Leikin, S
Kirschner, LS
Robey, P
Stratakis, CA
AF Tsang, K.
Starost, M. F.
Nesterova, M.
Boikos, S. A.
Watkins, T.
Almeida, M. Q.
Harran, M.
Li, A.
Collins, M. T.
Cheadle, C.
Mertz, E. L.
Leikin, S.
Kirschner, L. S.
Robey, P.
Stratakis, C. A.
TI Alternate Protein Kinase A Activity Identifies a Unique Population of
Stromal Cells in Adult Bone.
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010)
CY JUN 19-22, 2010
CL San Diego, CA
SP Endocrine Society
C1 [Tsang, K.; Nesterova, M.; Boikos, S. A.; Almeida, M. Q.; Harran, M.; Li, A.; Stratakis, C. A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Watkins, T.; Cheadle, C.] Johns Hopkins Univ, Baltimore, MD USA.
[Collins, M. T.; Robey, P.] NIDCR, NIH, Bethesda, MD USA.
[Mertz, E. L.; Leikin, S.] NICHD, NIH, Bethesda, MD USA.
[Kirschner, L. S.] Ohio State Univ, Columbus, OH 43210 USA.
RI Robey, Pamela/H-1429-2011
OI Robey, Pamela/0000-0002-5316-5576
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0163-769X
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2010
VL 31
IS 3
SU 1
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 652FV
UT WOS:000281989403150
ER
PT J
AU Wei, Q
Skarulis, M
Raghavachari, N
Xu, X
Munson, P
Nieman, L
AF Wei, Q.
Skarulis, M.
Raghavachari, N.
Xu, X.
Munson, P.
Nieman, L.
TI Circadian Patterns of Peripheral Blood Gene Expression.
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010)
CY JUN 19-22, 2010
CL San Diego, CA
SP Endocrine Society
C1 [Wei, Q.; Nieman, L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Skarulis, M.] NIDDK, Bethesda, MD USA.
[Raghavachari, N.; Xu, X.] NHLBI, Bethesda, MD 20892 USA.
[Munson, P.] CIT, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0163-769X
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2010
VL 31
IS 3
SU 1
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 652FV
UT WOS:000281989403113
ER
PT J
AU Whirledge, SD
Dixon, D
Cidlowski, JA
AF Whirledge, S. D.
Dixon, D.
Cidlowski, J. A.
TI Glucorticoid Regulation of Gene Expression in Uterine Leiomyomas.
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010)
CY JUN 19-22, 2010
CL San Diego, CA
SP Endocrine Society
C1 [Whirledge, S. D.; Dixon, D.; Cidlowski, J. A.] NIEHS, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0163-769X
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2010
VL 31
IS 3
SU 1
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 652FV
UT WOS:000281989403359
ER
PT J
AU Wilde, JI
Rabbee, N
Chudova, D
Wang, H
Friedlander, C
Wang, E
Pagan, M
Tom, E
Reynolds, J
Rigl, CT
Wang, CC
Friedman, L
Lanman, RB
Zeiger, M
Kebebew, E
Rosai, J
LiVolsi, VA
Kennedy, GC
AF Wilde, J. I.
Rabbee, N.
Chudova, D.
Wang, H.
Friedlander, C.
Wang, E.
Pagan, M.
Tom, E.
Reynolds, J.
Rigl, C. T.
Wang, C. C.
Friedman, L.
Lanman, R. B.
Zeiger, M.
Kebebew, E.
Rosai, J.
LiVolsi, V. A.
Kennedy, G. C.
TI A Multi-Gene Test for Accurate Classification of Thyroid Nodules.
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010)
CY JUN 19-22, 2010
CL San Diego, CA
SP Endocrine Society
C1 [Wilde, J. I.; Rabbee, N.; Chudova, D.; Wang, H.; Friedlander, C.; Wang, E.; Pagan, M.; Tom, E.; Reynolds, J.; Rigl, C. T.; Wang, C. C.; Friedman, L.; Lanman, R. B.; Zeiger, M.; Kennedy, G. C.] Veracyte Inc, San Francisco, CA USA.
[Kebebew, E.] Johns Hopkins Sch Med, Baltimore, MD USA.
[Rosai, J.] NCI, Bethesda, MD 20892 USA.
[LiVolsi, V. A.] Ctr Consulenze Anatom Patol Oncol, Milan, Italy.
Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0163-769X
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2010
VL 31
IS 3
SU 1
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 652FV
UT WOS:000281989401541
ER
PT J
AU Wu, YJ
Sun, H
Vijayakumar, A
Yao, S
Liu, CY
Yakar, S
LeRoith, D
AF Wu, Yingjie
Sun, Hui
Vijayakumar, Archana
Yao, Sheng
Liu, Chengyu
Yakar, Shoshana
LeRoith, Derek
TI beta Cell Specific Disruption of the Growth Hormone Receptor Does Not
Affect beta Cell Mass but May Affect Its Function.
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010)
CY JUN 19-22, 2010
CL San Diego, CA
SP Endocrine Society
C1 [Wu, Yingjie; Sun, Hui; Vijayakumar, Archana; Yao, Sheng; Yakar, Shoshana; LeRoith, Derek] Mt Sinai Sch Med, New York, NY USA.
[Liu, Chengyu] NHLBI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0163-769X
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2010
VL 31
IS 3
SU 1
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 652FV
UT WOS:000281989403238
ER
PT J
AU Xekouki, P
Azevedo, MF
Pasini, B
Lytras, A
Lange, E
Keil, M
Pacak, K
Horvath, A
Tolis, G
Stratakis, CA
AF Xekouki, P.
Azevedo, M. F.
Pasini, B.
Lytras, A.
Lange, E.
Keil, M.
Pacak, K.
Horvath, A.
Tolis, G.
Stratakis, C. A.
TI Acromegaly and Familial Paragangliomas: A New Syndrome?.
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010)
CY JUN 19-22, 2010
CL San Diego, CA
SP Endocrine Society
C1 [Xekouki, P.; Azevedo, M. F.; Lange, E.; Keil, M.; Pacak, K.; Horvath, A.; Stratakis, C. A.] Natl Inst Hlth, Bethesda, MD USA.
[Pasini, B.] Univ Turin, I-10124 Turin, Italy.
[Lytras, A.; Tolis, G.] Hippocrate Gen Hosp Athens, Athens, Greece.
NR 1
TC 0
Z9 0
U1 0
U2 1
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0163-769X
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2010
VL 31
IS 3
SU 1
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 652FV
UT WOS:000281989401079
ER
PT J
AU Zhu, XG
Cheng, SY
AF Zhu, X. G.
Cheng, S. Y.
TI NCoR Regulates Thyroid Hormone Receptor Isoform-Dependent Adipogenesis.
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010)
CY JUN 19-22, 2010
CL San Diego, CA
SP Endocrine Society
C1 [Zhu, X. G.; Cheng, S. Y.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0163-769X
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2010
VL 31
IS 3
SU 1
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 652FV
UT WOS:000281989402592
ER
PT J
AU Ziegler, RG
Fuhrman, BJ
Xu, X
Gail, MH
Keefer, LK
Veenstra, TD
Hoover, RN
AF Ziegler, R. G.
Fuhrman, B. J.
Xu, X.
Gail, M. H.
Keefer, L. K.
Veenstra, T. D.
Hoover, R. N.
TI In Asian-American Women, Westernization Influences Estrogen Metabolism,
but Not Total Estrogen Production.
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010)
CY JUN 19-22, 2010
CL San Diego, CA
SP Endocrine Society
C1 [Ziegler, R. G.; Fuhrman, B. J.; Gail, M. H.; Hoover, R. N.] NCI, Bethesda, MD 20892 USA.
[Xu, X.; Veenstra, T. D.] SAIC Frederick Inc, Frederick, MD USA.
[Keefer, L. K.] NCI, Frederick, MD 21701 USA.
RI Keefer, Larry/N-3247-2014
OI Keefer, Larry/0000-0001-7489-9555
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0163-769X
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2010
VL 31
IS 3
SU 1
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 652FV
UT WOS:000281989403048
ER
PT J
AU Naidich, M
Shterntal, B
Furman, R
Pawson, AJ
Jabbour, HN
Morgan, K
Millar, RP
Jia, JJ
Tomic, M
Stojilkovic, S
Stern, N
Naor, Z
AF Naidich, Michal
Shterntal, Boris
Furman, Ran
Pawson, Adam J.
Jabbour, Henry N.
Morgan, Kevin
Millar, Robert P.
Jia, Jingjing
Tomic, Melanija
Stojilkovic, Stanko
Stern, Naftali
Naor, Zvi
TI Elucidation of Mechanisms of the Reciprocal Cross Talk between
Gonadotropin-Releasing Hormone and Prostaglandin Receptors
SO ENDOCRINOLOGY
LA English
DT Article
ID FOLLICLE-STIMULATING-HORMONE; CYTOSOLIC PHOSPHOLIPASE A(2);
ARACHIDONIC-ACID; CYCLOOXYGENASE-2 EXPRESSION; GNRH RECEPTOR; CELLS;
ACTIVATION; KINASE; BETA; MAPK
AB We recently described a novel GnRH receptor signaling pathway mediated by the prostaglandins (PGs) F(2)alpha and PGI(2), which acts through an autocrine/paracrine modality to limit autoregulation of the GnRH receptor and inhibit LH but not FSH release. Here we further explore the cross talk between GnRH and the PG receptors. GnRH stimulates arachidonic acid (AA) release from L beta T2 gonadotrope cells via the Ca(2+)-independent phospholipase A(2) (iPLA(2)) and not via the more common Ca(2+)-dependent cytosolic phospholipase A(2)alpha(cPLA(2)alpha). AA release was followed by a marked induction of cyclooxygenase (COX)-1 and COX-2 by GnRH via the protein kinase C/c-Src/phosphatidylinositol 3-kinase/MAPK pathway. COX-2 transcription by GnRH is mediated by the two nuclear factor-kappa B sites and the CCAAT/enhancer-binding protein site within its promoter. Indeed, GnRH stimulates p65/RelA phosphorylation (22-fold) in L beta T2 cells and the two nuclear factor-kappa B sites apparently act as a composite response element. Although GnRH stimulates cAMP formation in L beta T2 cells, we found no role for cAMP acting via the cAMP response element site in the COX-2 promoter. PGF(2 alpha), PGI2, or PGE(2) had no effect on GnRH-stimulated ERK, c-Jun N-terminal kinase, and p38MAPK activation or on GnRH-and high K(+)-stimulated intracellular Ca(2+) elevation in L beta T2 and gonadotropes in primary culture. Although, PGF(2 alpha) , PGI2, and PGE2 reduced GnRH-stimulated cAMP formation, we could not correlate it to the inhibition of GnRH receptor expression, which is exerted only by PGF(2 alpha) and PGI(2). Hence, the inhibition by PGF(2 alpha) and PGI(2) of the autoregulation of GnRH receptor expression is most likely mediated via inhibition of GnRH-stimulated phosphoinositide turnover and not by inhibition of Ca(2+) elevation and MAPK activation. (Endocrinology 151: 2700-2712, 2010)
C1 [Naidich, Michal; Shterntal, Boris; Furman, Ran; Naor, Zvi] Tel Aviv Univ, Dept Biochem, George S Wise Fac Life Sci, IL-69978 Ramat Aviv, Israel.
[Pawson, Adam J.; Jabbour, Henry N.; Morgan, Kevin; Millar, Robert P.] Queens Med Res Inst, Ctr Reprod Biol, Med Res Council Human Reprod Sci Unit, Edinburgh EH16 4TJ, Midlothian, Scotland.
[Jia, Jingjing] N Carolina State Univ, Dept Mol & Struct Biochem, Raleigh, NC 27695 USA.
[Tomic, Melanija; Stojilkovic, Stanko] NICHHD, Sect Cellular Signaling, NIH, Bethesda, MD 20892 USA.
[Naor, Zvi] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Inst Endocrinol Metab & Hypertens, IL-64239 Tel Aviv, Israel.
Tel Aviv Univ, Sackler Fac Med, IL-64239 Tel Aviv, Israel.
RP Naor, Z (reprint author), Tel Aviv Univ, Dept Biochem, IL-69978 Tel Aviv, Israel.
EM zvin@tauex.tau.ac.il
RI Tomic, Melanija/C-3371-2016; Pawson, Adam/Q-5678-2016
OI Pawson, Adam/0000-0003-2280-845X
FU Medical Research Council (United Kingdom); Israel Science Foundation
[221/05]; German-Israeli Foundation for Research and Development
[I-751-168.2/2002]; U.S.-Israel Binational Science Foundation [2007057];
Adams Super-Center for Brain Studies at Tel-Aviv University
FX This work was supported by the Medical Research Council (United Kingdom)
(to R.P.M), the Israel Science Foundation (Grant 221/05), the
German-Israeli Foundation for Research and Development (Grant
I-751-168.2/2002), U.S.-Israel Binational Science Foundation (Grant
2007057), and the Adams Super-Center for Brain Studies at Tel-Aviv
University (to Z.N.).
NR 30
TC 7
Z9 7
U1 0
U2 1
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD JUN
PY 2010
VL 151
IS 6
BP 2700
EP 2712
DI 10.1210/en.2009-1335
PG 13
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 599XY
UT WOS:000277948800032
PM 20392830
ER
PT J
AU Klenke, U
Constantin, S
Wray, S
AF Klenke, Ulrike
Constantin, Stephanie
Wray, Susan
TI Neuropeptide Y Directly Inhibits Neuronal Activity in a Subpopulation of
Gonadotropin-Releasing Hormone-1 Neurons via Y1 Receptors
SO ENDOCRINOLOGY
LA English
DT Article
ID RECTIFYING POTASSIUM CURRENT; EMBRYONIC OLFACTORY PLACODE; LHRH NEURONS;
FOOD-INTAKE; PEPTIDE YY; EXPLANT CULTURES; ARCUATE NUCLEUS;
RHESUS-MONKEY; K+ CHANNELS; NPY NEURONS
AB Neuropeptide Y (NPY), a member of the pancreatic polypeptide family, is an orexigenic hormone. GnRH-1 neurons express NPY receptors. This suggests a direct link between metabolic function and reproduction. However, the effect of NPY on GnRH-1 cells has been variable, dependent on metabolic and reproductive status of the animal. This study circumvents these issues by examining the role of NPY on GnRH-1 neuronal activity in an explant model that is based on the extra-central nervous system origin of GnRH-1 neurons. These prenatal GnRH-1 neurons express many receptors found in GnRH-1 neurons in the brain and use similar transduction pathways. In addition, these GnRH-1 cells exhibit spontaneous and ligand-induced oscillations in intracellular calcium as well as pulsatile calcium-controlled GnRH-1 release. Single-cell PCR determined that prenatal GnRH-1 neurons express the G protein-coupled Y1 receptor (Y1R). To address the influence of NPY on GnRH-1 neuronal activity, calcium imaging was used to monitor individual and population dynamics. NPY treatment, mimicked with Y1R agonist, significantly decreased the number of calcium peaks per minute in GnRH-1 neurons and was prevented by a Y1R antagonist. Pertussis toxin blocked the effect of NPY on GnRH-1 neuronal activity, indicating the coupling of Y1R to inhibitory G protein. The NPY-induced inhibition was independent of the adenylate cyclase pathway but mediated by the activation of G protein-coupled inwardly rectifying potassium channels. These results indicate that at an early developmental stage, GnRH-1 neuronal activity can be directly inhibited by NPY via its Y1R. (Endocrinology 151: 2736-2746, 2010)
C1 [Klenke, Ulrike; Constantin, Stephanie; Wray, Susan] Natl Inst Neurol Disorders & Stroke, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
[Constantin, Stephanie] Univ Otago, Ctr Neuroendocrinol, Dept Physiol, Dunedin 9054, New Zealand.
RP Wray, S (reprint author), Natl Inst Neurol Disorders & Stroke, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
EM wrays@mail.nih.gov
RI Constantin, Stephanie/C-5264-2009;
OI Constantin, Stephanie/0000-0003-0596-9737; wray,
susan/0000-0001-7670-3915
FU National Institute of Neurological Disorders and Stroke, National
Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute of Neurological Disorders and Stroke, National
Institutes of Health.
NR 66
TC 32
Z9 33
U1 0
U2 3
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD JUN
PY 2010
VL 151
IS 6
BP 2736
EP 2746
DI 10.1210/en.2009-1198
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 599XY
UT WOS:000277948800035
PM 20351316
ER
PT J
AU Allan, CM
Couse, JF
Simanainen, U
Spaliviero, J
Jimenez, M
Rodriguez, K
Korach, KS
Handelsman, DJ
AF Allan, Charles M.
Couse, John F.
Simanainen, Ulla
Spaliviero, Jenny
Jimenez, Mark
Rodriguez, Karina
Korach, Kenneth S.
Handelsman, David J.
TI Estradiol Induction of Spermatogenesis Is Mediated via an Estrogen
Receptor-alpha Mechanism Involving Neuroendocrine Activation of
Follicle-Stimulating Hormone Secretion
SO ENDOCRINOLOGY
LA English
DT Article
ID HYPOGONADAL HPG MOUSE; BETA ER-BETA; ANDROGEN RECEPTOR; SERTOLI-CELLS;
LUTEINIZING-HORMONE; MICE LACKING; REPRODUCTIVE PHENOTYPES; TARGETED
DISRUPTION; FEMALE MICE; WILD-TYPE
AB Both testosterone and its nonaromatizable metabolite dihydrotestosterone (DHT) induce spermatogenesis in gonadotropin-deficient hpg mice. Surprisingly, because aromatization is not required, estradiol (E2) also induces spermatogenesis and increases circulating FSH in hpg mice, but the mechanism remains unclear. We studied E2-induced spermatogenesis in hpg mice on an estrogen receptor (ER)-alpha (hpg/alpha ERKO) or ER beta (hpg/beta ERKO) knockout or wild-type ER (hpg/WT) background treated with subdermal E2 or DHT implants for 6 wk. In hpg/WT and hpg/beta ERKO, but not hpg/alpha ERKO mice, E2 increased testis and epididymal weight, whereas DHT-induced increases were unaffected by ER alpha or ER beta inactivation. E2 but not DHT treatment increased serum FSH (but not LH) in hpg/WT and hpg/beta ERKO but not hpg/alpha ERKO hpg mice. DHT or E2 alone increased (premeiotic) spermatogonia and (meiotic) spermatocytes without significant change in Sertoli cell numbers. DHT alone increased postmeiotic spermatids, regardless of ER presence, compared with variable ER alpha-dependent E2 postmeiotic responses. An ER alpha-mediated effect was confirmed by treating hpg mice for 6 wk by subdermal selective ER-alpha (16 alpha-LE(2)) or ER beta (8 beta-VE(2)) agonist implants. ER alpha (but not ER beta) agonist increased testis and epididymal weight, Sertoli cell, spermatogonia, meiotic, and postmeiotic germ cell numbers. Only ER alpha agonist markedly increased serum FSH, whereas either agonist induced small rises in serum LH. Administration of ER alpha agonist or E2 in the presence of functional ER alpha induced prominent gene expression of specific Sertoli (Eppin, Rhox5) and Leydig cell (Cyp11a1, Hsd3b1) markers. We conclude that E2-induced spermatogenesis in hpg mice involves an ER alpha-dependent neuroendocrine mechanism increasing blood FSH and Sertoli cell function. (Endocrinology 151: 2800-2810, 2010)
C1 [Allan, Charles M.; Simanainen, Ulla; Spaliviero, Jenny; Jimenez, Mark; Handelsman, David J.] Univ Sydney, Concord Hosp, ANZAC Res Inst, Androl Lab, Sydney, NSW 2139, Australia.
[Couse, John F.] Taconic Inc, Rensselaer, NY 12144 USA.
[Couse, John F.; Rodriguez, Karina; Korach, Kenneth S.] NIEHS, Receptor Biol Sect, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA.
RP Handelsman, DJ (reprint author), Univ Sydney, Concord Hosp, ANZAC Res Inst, Androl Lab, Sydney, NSW 2139, Australia.
EM djh@anzac.edu.au
OI Korach, Kenneth/0000-0002-7765-418X
FU National Health and Medical Research Council [464857]; Australian
Research Council [DP0881690]; Division of Intramural Research, National
Institute of Environmental Health Sciences [Z01ES70065]
FX This work was supported by the National Health and Medical Research
Council (464857 to C.M.A. and D.J.H.), Australian Research Council
(DP0881690 to C.M.A. and D.J.H.), and the Division of Intramural
Research, National Institute of Environmental Health Sciences
(Z01ES70065 to K.S.K.).
NR 55
TC 31
Z9 34
U1 1
U2 6
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD JUN
PY 2010
VL 151
IS 6
BP 2800
EP 2810
DI 10.1210/en.2009-1477
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 599XY
UT WOS:000277948800041
PM 20410197
ER
PT J
AU Rodriguez, KF
Couse, JF
Jayes, FL
Hamilton, KJ
Burns, KA
Taniguchi, F
Korach, KS
AF Rodriguez, Karina F.
Couse, John F.
Jayes, Friederike L.
Hamilton, Katherine J.
Burns, Katherine A.
Taniguchi, Fuminori
Korach, Kenneth S.
TI Insufficient Luteinizing Hormone-Induced Intracellular Signaling
Disrupts Ovulation in Preovulatory Follicles Lacking Estrogen
Receptor-beta
SO ENDOCRINOLOGY
LA English
DT Article
ID PROSTAGLANDIN ENDOPEROXIDE SYNTHASE-2; GRANULOSA-CELL DIFFERENTIATION;
FOLLICULAR MATURATION; STIMULATING-HORMONE; IN-VITRO; ER-BETA; GROWTH;
EXPRESSION; PATHWAYS; MOUSE
AB Gonadotropin-stimulated estrogen receptor-beta (ER beta)-null preovulatory follicles exhibit submaximal estradiol production, insufficient acquisition of LH receptor, and attenuated expression of essential ovulatory genes. These observations lead to low ovulatory rates compared with wild-type (WT) follicles. We hypothesize that insufficient LH receptor results in reduced cAMP production after an ovulatory stimulus. Individual preantral follicles were cultured with FSH for 4 d and then induced to ovulate with a single dose of human chorionic gonadotropin (hCG). cAMP levels 1h after hCG were 50% lower in ER beta-null than WT follicles. To determine whether the lack of LH receptor, and resulting lack of cAMP, could be bypassed by direct activation of adenylyl cyclase, WT and ER beta-null follicles were induced to ovulate with forskolin. Ten micromolar forskolin doubled the ovulatory rate of ER beta-null follicles compared with treatment with hCG (similar to 50 vs. 25%, respectively). In WT follicles, 10 mu M forskolin reduced the ovulation rate compared with hCG (14 vs. 83%, respectively), indicating that high doses of forskolin inhibited WT ovulation. A 10 mu M concentration of forskolin induced cAMP levels in ER beta-null follicles that were comparable to levels produced in WT follicles after hCG and either partially or completely rescued the attenuated expression of LH-responsive genes. These data indicate that direct activation of adenylyl cyclase, resulting in increased production of cAMP, partially rescues the ovulatory response of ER beta-null follicles, suggesting that insufficient LH receptor and low cAMP levels contribute to their poor ovulatory rates. We also determined that ER beta-null ovaries exhibit an alteration in the activation of ERK1/2. Our evaluation of the ER beta-null ovarian phenotype indicates that ER beta plays a role in facilitating folliculogenesis. We show that expression of ER beta in preovulatory follicles is required for adequate cAMP production and propose that an optimal level of cAMP is required for hCG-stimulated ovulation. (Endocrinology 151: 2826-2834, 2010)
C1 [Korach, Kenneth S.] NIEHS, Environm Dis Med Program, Receptor Biol Sect, NIH, Res Triangle Pk, NC 27709 USA.
RP Korach, KS (reprint author), NIEHS, Environm Dis Med Program, Receptor Biol Sect, NIH, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM korach@niehs.nih.gov
OI Korach, Kenneth/0000-0002-7765-418X
FU National Institutes of Health, National Institute of Environmental
Health Sciences [Z01ES70065]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Environmental
Health Sciences Z01ES70065 (to K.S.K.).
NR 28
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U1 0
U2 0
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD JUN
PY 2010
VL 151
IS 6
BP 2826
EP 2834
DI 10.1210/en.2009-1446
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 599XY
UT WOS:000277948800044
PM 20378682
ER
PT J
AU Memarzadeh, F
AF Memarzadeh, Farhad
TI COMMENTS ON "EFFECT OF VENTILATION STRATEGIES ON INFECTION CONTROL
INSIDE OPERATING THEATRES"
SO ENGINEERING APPLICATIONS OF COMPUTATIONAL FLUID MECHANICS
LA English
DT Editorial Material
C1 NIH, Div Tech Resources, Bethesda, MD 20892 USA.
RP Memarzadeh, F (reprint author), NIH, Div Tech Resources, Bldg 10, Bethesda, MD 20892 USA.
EM memarzaf@ors.od.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU HONG KONG POLYTECHNIC UNIV, DEPT CIVIL & STRUCTURAL ENG
PI HONG KONG
PA HUNG HOM, KOWLOON, HONG KONG, 00000, PEOPLES R CHINA
SN 1994-2060
J9 ENG APPL COMP FLUID
JI Eng. Appl. Comp. Fluid Mech.
PD JUN
PY 2010
VL 4
IS 2
BP 326
EP 327
PG 2
WC Engineering, Multidisciplinary; Engineering, Mechanical; Mechanics
SC Engineering; Mechanics
GA 593IC
UT WOS:000277445600013
ER
PT J
AU Wilson, DM
Brooks, PJ
AF Wilson, David M., III
Brooks, Philip J.
TI The Mitochondrial Genome: Dynamics, Mechanisms of Repair, and a Target
in Disease and Therapy
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Editorial Material
ID EVOLUTION
C1 [Wilson, David M., III] NIA, Lab Mol Gerontol, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA.
[Brooks, Philip J.] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA.
RP Wilson, DM (reprint author), NIA, Lab Mol Gerontol, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA.
FU Intramural NIH HHS [Z01 AG000743-07]
NR 11
TC 0
Z9 0
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD JUN
PY 2010
VL 51
IS 5
BP 349
EP 351
DI 10.1002/em.20584
PG 3
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 614GI
UT WOS:000279043000001
PM 20544877
ER
PT J
AU Balaban, RS
AF Balaban, Robert S.
TI The Mitochondrial Proteome: A Dynamic Functional Program in Tissues and
Disease States
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Review
DE protein phosphorylation; diabetes; oxidative phosphorylation; metabolic
regulation
ID C-OXIDASE ACTIVITY; BOVINE HEART; PYRUVATE-DEHYDROGENASE; INHIBITOR
PROTEIN; S-NITROSYLATION; COMPLEX-I; SUBUNIT-I; PHOSPHORYLATION; LIVER;
METABOLISM
AB The nuclear DNA transcriptional programming of the mitochondria proteome varies dramatically between tissues depending on its functional requirements. This programming generally regulates all of the proteins associated with a metabolic or biosynthetic pathway associated with a given function, essentially regulating the maximum rate of the pathway while keeping the enzymes at the same molar ratio. This may permit the same regulatory mechanisms to function at low- and high-flux capacity situations. This alteration in total protein content results in rather dramatic changes in the mitochondria proteome between tissues. A tissues mitochondria proteome also changes with disease state, in Type 1 diabetes the liver mitochondrial proteome shifts to support ATP production, urea synthesis, and fatty acid oxidation. Acute flux regulation is modulated by numerous posttranslational events that also are highly variable between tissues. The most studied posttranslational modification is protein phosphorylation, which is found all of the complexes of oxidative phosphorylation and most of the major metabolic pathways. The functional significance of these modifications is currently a major area of research along with the kinase and phosphatase regulatory network. This near ubiquitous presence of protein phosphorylations, and other posttranslational events, in the matrix suggest that not all posttranslational events have functional significance. Screening methods are being introduced to detect the active or dynamic posttranslational sites to Focus attention on sites that might provide insight into regulatory mechanisms. Environ. Mol. Mutagen. 51:352-359, 2010. Published 2010 Wiley-Liss, Inc.(1)
C1 NHLBI, Cardiac Energet Lab, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Balaban, RS (reprint author), NHLBI, Cardiac Energet Lab, Dept Hlth & Human Serv, 9000 Rockville Pike,Bldg 10 Room B1D161, Bethesda, MD 20892 USA.
EM rsb@nih.gov
NR 50
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U1 2
U2 10
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD JUN
PY 2010
VL 51
IS 5
BP 352
EP 359
DI 10.1002/em.20574
PG 8
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 614GI
UT WOS:000279043000002
PM 20544878
ER
PT J
AU Goodman, M
Squibb, K
Youngstrom, E
Anthony, LG
Kenworthy, L
Lipkin, PH
Mattison, DR
LaKind, JS
AF Goodman, Michael
Squibb, Katherine
Youngstrom, Eric
Anthony, Laura Gutermuth
Kenworthy, Lauren
Lipkin, Paul H.
Mattison, Donald R.
LaKind, Judy S.
TI Using Systematic Reviews and Meta-Analyses to Support Regulatory
Decision Making for Neurotoxicants: Lessons Learned from a Case Study of
PCBs
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Review
DE domain; function testing; meta-analysis; neurodevelopment;
neurotoxicants; PCBs; risk assessment; weight of evidence
ID POLYCHLORINATED-BIPHENYLS; PRENATAL EXPOSURE; DICHLORODIPHENYL
DICHLOROETHENE; CHEMICAL-EXPOSURE; MOTOR DEVELOPMENT; PUBLICATION BIAS;
CHILDREN; DIOXINS; CONTAMINANTS; PERFORMANCE
AB BACKGROUND: Epidemiologic weight-of-evidence reviews to support regulatory decision making regarding the association between environmental chemical exposures and neurodevelopmental outcomes in children are often complicated by lack of consistency across studies.
OBJECTIVE: We examined prospective cohort studies evaluating the relation between prenatal and neonatal exposure to polychlorinated biphenyls (PCBs) and neurodevelopment in children to assess the feasibility of conducting a meta-analysis to support decision making.
DATA EXTRACTION/SYNTHESIS: We described studies in terms of exposure and end point categorization, statistical analysis, and reporting of results. We used this evaluation to assess the feasibility of grouping studies into reasonably uniform categories.
RESULTS: The current literature includes 11 cohorts of children for whom effects from prenatal or neonatal PCB exposures were assessed. The most consistently used tests included Brazelton's Neonatal Behavioral Assessment Scale, the neurologic optimality score in the neonatal period, the Bayley Scales of Infant Development at 5-8 months of age, and the McCarthy Scales of Children's Abilities in 5-year-olds. Despite administering the same tests at similar ages, the studies were too dissimilar to allow a meaningful quantitative examination of outcomes across cohorts.
CONCLUSIONS: These analyses indicate that our ability to conduct weight-of-evidence assessments of the epidemiologic literature on neurotoxicants may be limited, even in the presence of multiple studies, if the available study methods, data analysis, and reporting lack comparability. Our findings add support to previous calls for establishing consensus standards for the conduct, analysis, and reporting of epidemiologic studies in general, and for those evaluating the effects of potential neurotoxic exposures in particular.
C1 [LaKind, Judy S.] LaKind Associates LLC, Catonsville, MD 21228 USA.
[LaKind, Judy S.] Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA.
[LaKind, Judy S.] Penn State Coll Med, Milton S Hershey Med Ctr, Dept Pediat, Hershey, PA USA.
[Goodman, Michael] Emory Univ, Sch Publ Hlth, Dept Epidemiol, Atlanta, GA USA.
[Squibb, Katherine] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
[Youngstrom, Eric] Univ N Carolina, Dept Psychol, Chapel Hill, NC USA.
[Youngstrom, Eric] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
[Anthony, Laura Gutermuth; Kenworthy, Lauren] Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders, Washington, DC 20010 USA.
[Anthony, Laura Gutermuth; Kenworthy, Lauren] George Washington Univ, Sch Med, Dept Pediat, Washington, DC 20052 USA.
[Anthony, Laura Gutermuth; Kenworthy, Lauren] George Washington Univ, Sch Med, Dept Psychiat, Washington, DC USA.
[Kenworthy, Lauren] George Washington Univ, Sch Med, Dept Neurol, Washington, DC USA.
[Lipkin, Paul H.] Kennedy Krieger Inst, Ctr Dev & Learning, Baltimore, MD USA.
[Lipkin, Paul H.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA.
[Mattison, Donald R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, US Dept HHS, Bethesda, MD USA.
RP LaKind, JS (reprint author), LaKind Associates LLC, 106 Oakdale Ave, Catonsville, MD 21228 USA.
EM lakindassoc@comcast.net
RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013;
OI Mattison, Donald/0000-0001-5623-0874; Lipkin, Paul/0000-0002-9043-2581
FU Cefic-Long-range Research Initiative (LRI); Otsuka/Bristol Myers Squibb
FX This research was supported by a grant from Cefic-Long-range Research
Initiative (LRI). Cefic-LRI was nor involved in the design, collection,
management, analysis, or interpretation of the data or in the
preparation or approval of the manuscript.; J.S.L. consults to both
government and industry. P.H.L. was a consultant to Bristol Myers Squibb
from 2008 to 2009; he has no current actual or potential competing
financial interests. E.Y. received travel funding from Otsuka/Bristol
Myers Squibb in 2009. The other authors declare they have no actual or
potential competing financial interests.
NR 44
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U1 2
U2 10
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 JUN
PY 2010
VL 118
IS 6
BP 727
EP 734
DI 10.1289/ehp.0901835
PG 8
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 608NP
UT WOS:000278591300014
PM 20176542
ER
PT J
AU Schecter, A
Colacino, J
Haffner, D
Patel, K
Opel, M
Papke, O
Birnbaum, L
AF Schecter, Arnold
Colacino, Justin
Haffner, Darrah
Patel, Keyur
Opel, Matthias
Paepke, Olaf
Birnbaum, Linda
TI Perfluorinated Compounds, Polychlorinated Biphenyls, and Organochlorine
Pesticide Contamination in Composite Food Samples from Dallas, Texas,
USA
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE food; PCBs; pesticides; PFCs; United States
ID NUTRITION EXAMINATION SURVEY; ETHER PBDE LEVELS; PERFLUOROOCTANE
SULFONATE; UNITED-STATES; CHEMICAL-MIXTURES; DIETARY EXPOSURE; HEALTH;
PCBS; POPULATION; MARKET
AB OBJECTIVES: The objective of this article is to extend our previous studies of persistent organic pollutant (POP) contamination of U.S. food by measuring perfluorinated compounds (PFCs), organochlorine pesticides, and polychlorinated biphenyls (PCBs) in composite food samples. This study is part of a larger study reported in two articles, the other of which reports levels of poly-brominated diphenyl ethers and hexabromocyclododecane brominated flame retardants in these composite foods [Schecter et al. 2010. Polybrominated diphenyl ethers (PBDEs) and hexabromo-cyclodecane (HBCD) in composite U.S. food samples, Environ Health Perspect 118:357-362].
METHODS: In this study we measured concentrations of 32 organochlorine pesticides, 7 PCBs, and 11 PFCs in composite samples of 31 different types of food (310 individual food samples) purchased from supermarkets in Dallas, Texas (USA), in 2009. Dietary intake of these chemicals was calculated for an average American.
RESULTS: Contamination varied greatly among chemical and food types. The highest level of pesticide contamination was from the dichlorodiphenyltrichloroethane (DDT) metabolite p,p'-dichlorodiphenyldichloroethylene, which ranged from 0.028 ng/g wet weight (ww) in whole milk yogurt to 2.3 ng/g ww in catfish fillets. We found PCB congeners (28, 52, 101, 118, 138, 153, and 180) primarily in fish, with highest levels in salmon (PCB-153, 1.2 ng/g ww; PCB-138, 0.93 ng/g ww). For PFCs, we detected perfluorooctanoic acid (PFOA) in 17 of 31 samples, ranging from 0.07 ng/g in potatoes to 1.80 ng/g in olive oil. In terms of dietary intake, DDT and DDT metabolites, endosulfans, aldrin, PCBs, and PFOA were consumed at the highest levels.
CONCLUSION: Despite product bans, we found POPs in U.S. food, and mixtures of these chemicals are consumed by the American public at varying levels. This suggests the need to expand testing of food for chemical contaminants.
C1 [Schecter, Arnold; Patel, Keyur] Univ Texas Sch Publ Hlth Dallas, Div Environm & Occupat Hlth Sci, Dallas, TX 75390 USA.
[Colacino, Justin] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA.
[Haffner, Darrah] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Opel, Matthias; Paepke, Olaf] Eurofins GfA GmbH, Hamburg, Germany.
[Birnbaum, Linda] NIEHS, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
RP Schecter, A (reprint author), Univ Texas Sch Publ Hlth Dallas, Div Environm & Occupat Hlth Sci, 6011 Harry Hines Blvd,V8-112, Dallas, TX 75390 USA.
EM arnold.schecter@utsouthwestern.edu
FU Gustavus and Louise Pfeiffer Research Foundation
FX We acknowledge the Gustavus and Louise Pfeiffer Research Foundation for
their generous funding of this research.
NR 52
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U1 8
U2 59
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 JUN
PY 2010
VL 118
IS 6
BP 796
EP 802
DI 10.1289/ehp.0901347
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 608NP
UT WOS:000278591300024
PM 20146964
ER
PT J
AU Dennis, LK
Lynch, CF
Sandler, DP
Alavanja, MCR
AF Dennis, Leslie K.
Lynch, Charles F.
Sandler, Dale P.
Alavanja, Michael C. R.
TI Pesticide Use and Cutaneous Melanoma in Pesticide Applicators in the
Agricultural Heath Study
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE arsenic; farmers; melanoma; pesticides
ID SKIN-CANCER; MALIGNANT-MELANOMA; BLACKFOOT DISEASE; DRINKING-WATER;
DNA-DAMAGE; EXPOSURE; HEALTH; RISK; FARMERS; WORKERS
AB BACKGROUND: Melanoma rates continue to increase; however, few risk factors other than sun sensitivity and ultraviolet radiation (including sun exposure) have been identified. Although studies of farmers have shown an excess risk of melanoma and other skin cancers, it is unclear how much of this is related to sun exposure compared with other agricultural exposures.
METHODS: We examined dose-response relationships for 50 agricultural pesticides and cutaneous melanoma incidence in the Agricultural Health Study cohort of licensed pesticide applicators, along with ever use of older pesticides that contain arsenic. Logistic regression was used to examine odds ratios (ORs) and 95% confidence intervals (CIs) associated with pesticide exposure adjusted for age, sex, and other potential confounders.
RESULTS: We found significant associations between cutaneous melanoma and maneb/mancozeb (>= 63 exposure days: OR = 2.4; 95% CI, 1.2-4.9; trend p = 0.006), parathion (>= 56 exposure days: OR = 2.4; 95% CI, 1.3-4.4; trend p = 0.003), and carbaryl (>= 56 exposure days: OR = 1.7; 95% CI, 1.1-2.5; trend p = 0.013). Other associations with benomyl and ever use of arsenical pesticides were also suggested.
CONCLUSIONS: Most previous melanoma literature has focused on host factors and sun exposure. Our research shows an association between several pesticides and melanoma, providing support for the hypotheses that agricultural chemicals may be another important source of melanoma risk.
C1 [Dennis, Leslie K.; Lynch, Charles F.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA 52242 USA.
[Sandler, Dale P.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Alavanja, Michael C. R.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
RP Dennis, LK (reprint author), Univ Iowa, Coll Publ Hlth, Dept Epidemiol, 200 Hawkins Dr,C21H GH, Iowa City, IA 52242 USA.
EM leslie-dennis@uiowa.edu
OI Sandler, Dale/0000-0002-6776-0018
FU National Institutes of Health (NIH), National Cancer Institute
[Z01-CP010119, K07CA104556]; National Institute of Environmental Health
Sciences [Z01-ESO49030]
FX This research was supported in part by the intramural research programs
of the National Institutes of Health (NIH), the National Cancer
Institute (Z01-CP010119), and the National Institute of Environmental
Health Sciences (Z01-ESO49030) and by the extramural research programs
of the NIH and the National Cancer Institute (K07CA104556). The authors
declare they have no actual or potential competing financial interests.
NR 43
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U2 14
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 JUN
PY 2010
VL 118
IS 6
BP 812
EP 817
DI 10.1289/ehp.0901518
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 608NP
UT WOS:000278591300026
PM 20164001
ER
PT J
AU Moore, PD
Yedjou, CG
Tchounwou, PB
AF Moore, Pamela D.
Yedjou, Clement G.
Tchounwou, Paul B.
TI Malathion-Induced Oxidative Stress, Cytotoxicity, and Genotoxicity in
Human Liver Carcinoma (HepG(2)) Cells
SO ENVIRONMENTAL TOXICOLOGY
LA English
DT Article
DE malathion; cytotoxicity; lipid peroxidation; DNA damage; HepG(2) cells
ID LEUKEMIA HL-60 CELLS; LIPID-PEROXIDATION; IN-VITRO; ARSENIC TRIOXIDE;
DNA-DAMAGE; RAT-BRAIN; EXPOSURE; TOXICITY; ACID; INSECTICIDES
AB Malathion is an organophosphate pesticide that is known for its high toxicity to insects and low to moderate potency to humans and other mammals. Its toxicity has been associated with the inhibition of acetylcholinesterase activity, leading to the interference with the transmission of nerve impulse, accumulation of acetylcholin at synaptic junctions, and subsequent induction of adverse health effects including headache, dizziness, nausea, vomiting, bradycardia, and miosis. Oxidative stress (OS) has been reported as a possible mechanism of malathion toxicity in humans. Hence, the aim of this study was to examine the role of OS in malathion-induced cytotoxicity and genotoxicity. To achieve this goal, MIT, lipid peroxidation, and single cell gel electrophoresis (Comet) assays were performed, respectively, to evaluate the levels of cell viability, malondialdehyde (MDA) production, and DNA damage in human liver carcinoma (HepG(2)) cells. Study results indicated that malathion is mitogenic at lower levels of exposure, and cytotoxic at higher levels of exposure. Upon 48 h of exposure, the average percentages of cell viability were 100% +/- 11%, 117% +/- 15%, 86% +/- 15%, 35% +/- 9%, and 27% +/- 7% for 0, 6, 12, 18, and 24 mM, respectively. In the lipid peroxidation assay, the concentrations of MDA produced were 12.55 +/- 0.16, 20.65 +/- 0.27, 31.1 +/- 0.40, 34.75 +/- 0.45, and 15.1 +/- 0.20 mu M in 0, 6, 12, 18, and 24 mM malathion, respectively. The Comet assay showed a significant increase in DNA damage at the 24 mM malathion exposure. Taken together, our results indicate that malathion exposure at higher concentrations induces cytotoxic and genotoxic effects in HepG(2) cells, and its toxicity may be mediated through OS as evidenced by a significant production of MDA, an end product of lipid peroxidation. (C) 2009 Wiley Periodicals, Inc. Environ Toxicol 25: 221-226, 2010.
C1 [Moore, Pamela D.; Yedjou, Clement G.; Tchounwou, Paul B.] Jackson State Univ, Mol Toxicol Res Lab, NIH RCMI, Ctr Environm Hlth,Coll Sci Engn & Technol, Jackson, MS 39217 USA.
RP Tchounwou, PB (reprint author), Jackson State Univ, Mol Toxicol Res Lab, NIH RCMI, Ctr Environm Hlth,Coll Sci Engn & Technol, 1400 Lynch St,Box 18540, Jackson, MS 39217 USA.
EM paul.b.tchounwou@jsums.edu
FU National Institutes of Health (RCMI-Center for Environmental Health)
[2G12RR13459-11]; Department of the Army Cooperative, Jackson State
University [W912HZ-04-2-0002]
FX Contract grant sponsor: National Institutes of Health (RCMI-Center for
Environmental Health).; Contract grant number: 2G12RR13459-11.; Contract
grant sponsor: Department of the Army Cooperative, Jackson State
University.; Contract grant number: W912HZ-04-2-0002.
NR 32
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U1 2
U2 9
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1520-4081
J9 ENVIRON TOXICOL
JI Environ. Toxicol.
PD JUN
PY 2010
VL 25
IS 3
BP 221
EP 226
DI 10.1002/tox.20492
PG 6
WC Environmental Sciences; Toxicology; Water Resources
SC Environmental Sciences & Ecology; Toxicology; Water Resources
GA 596MK
UT WOS:000277689000002
PM 19399848
ER
PT J
AU Roche, B
Rohani, P
AF Roche, Benjamin
Rohani, Pejman
TI Environmental transmission scrambles coexistence patterns of avian
influenza viruses
SO EPIDEMICS
LA English
DT Article
DE Avian influenza; Strain competition; Mathematical modeling
AB Despite the recent accumulation of theoretical and empirical studies on avian influenza viruses (AIVs), the interactions among the diverse pool of strains remain poorly understood. One potential reason is multiple transmission routes. In this paper, we explore the behavior of a two-strain mathematical model of AIV dynamics with lifelong immunity to understand how the combination of direct and environmental transmission (via a persistent viral reservoir) determines strains coexistence and dominance. We find that coexistence requires the magnitude of basic reproductive ratios of the strains to be identical for each transmission route (R-0(dir) and R-0(env)) when cross-immunity is assumed to be perfect. Coexistence may be also possible when one strain is only directly transmitted and the contribution by environmental transmission is high. When we relax this assumption, the level of cross-protection does not modify coexistence criteria when strains are mainly environmentally transmitted, in contrast to the case where direct transmission dominates. Finally, when competitive exclusion is observed, the strain with the largest contribution from direct transmission outcompetes the other through competition for viral particle acquisition. Overall, we conclude that environmental transmission can affect the patterns of coexistence predicted by direct transmission models in complex ways. (C) 2010 Elsevier B. V. All rights reserved.
C1 [Roche, Benjamin; Rohani, Pejman] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
[Rohani, Pejman] Univ Michigan, Ctr Study Complex Syst, Ann Arbor, MI 48109 USA.
[Rohani, Pejman] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Roche, B (reprint author), North Univ, Dept Ecol & Evolutionary Biol, 2014 Kraus Nat Sci Bldg 830, Ann Arbor, MI 49108 USA.
EM benroche@umich.edu
OI Roche, Benjamin/0000-0001-7975-4232
FU Centers for Disease Control and Prevention [5U19Cl000401]; James S.
McDonnell Foundation; National Science Foundation [DEB-0917853]; RAPIDD
of the Science & Technology Directorate, Department of Homeland
Security; Fogarty International Center, National Institutes of Health
FX This work is supported by the Centers for Disease Control and Prevention
(5U19Cl000401), the James S. McDonnell Foundation, and the National
Science Foundation (DEB-0917853). P. R. was also supported by the RAPIDD
program of the Science & Technology Directorate, Department of Homeland
Security, and the Fogarty International Center, National Institutes of
Health.
NR 48
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U1 1
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1755-4365
J9 EPIDEMICS-NETH
JI Epidemics
PD JUN
PY 2010
VL 2
IS 2
BP 92
EP 98
DI 10.1016/j.epidem.2010.03.002
PG 7
WC Infectious Diseases
SC Infectious Diseases
GA V21UW
UT WOS:000208233500005
PM 21352779
ER
PT J
AU Newall, AT
Viboud, C
Wood, JG
AF Newall, A. T.
Viboud, C.
Wood, J. G.
TI Influenza-attributable mortality in Australians aged more than 50 years:
a comparison of different modelling approaches
SO EPIDEMIOLOGY AND INFECTION
LA English
DT Article
DE Age groups; Australia; infectious disease; influenza; mortality;
time-series models
ID RESPIRATORY SYNCYTIAL VIRUS; UNITED-STATES; DEATHS; IMPACT
AB This study aimed to compare systematically approaches to estimating influenza-attributable mortality in older Australians. Using monthly age-specific death data together with viral surveillance counts for influenza and respiratory syncytial virus, we explored two of the most frequently used methods of estimating excess influenza-attributable disease: Poisson and Serfling regression models. These approaches produced consistent age and temporal patterns in estimates of influenza-attributable mortality in older Australians but some variation in the magnitude of the disease burden. Of Australians aged >50 years, average annual estimated influenza-attributable deaths (all cause) ranged from 2314 to 3457 for the Serfling and Poisson regression models, respectively. The excess influenza-attributable disease burden was substantial under all approaches.
C1 [Newall, A. T.] Univ New S Wales, Sch Publ Hlth & Community Med, Fac Med, Sydney, NSW 2052, Australia.
[Newall, A. T.; Wood, J. G.] Childrens Hosp Westmead, Natl Ctr Immunisat Res & Surveillance Vaccine Pre, Westmead, NSW, Australia.
[Newall, A. T.; Wood, J. G.] Univ Sydney, Sydney, NSW 2006, Australia.
[Viboud, C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Newall, AT (reprint author), Univ New S Wales, Sch Publ Hlth & Community Med, Fac Med, Sydney, NSW 2052, Australia.
EM a.newall@unsw.edu.au
FU Influenza Specialist Group (ISG); GlaxoSmithKline Australia
FX A.T.N. and J.G.W. have conducted prior projects on influenza disease
burden which were funded by the Influenza Specialist Group (ISG). A.T.N.
and J.G.W. have received research grants for other projects from
GlaxoSmithKline Australia. C.V. has no conflicts of interest to declare.
NR 21
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U1 0
U2 1
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0950-2688
J9 EPIDEMIOL INFECT
JI Epidemiol. Infect.
PD JUN
PY 2010
VL 138
IS 6
BP 836
EP 842
DI 10.1017/S095026880999118X
PG 7
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 602ZN
UT WOS:000278177800005
PM 19941685
ER
PT J
AU Evans, MK
Lepkowski, JM
Powe, NR
LaVeist, T
Kuczmarski, MF
Zonderman, AB
AF Evans, Michele K.
Lepkowski, James M.
Powe, Neil R.
LaVeist, Thomas
Kuczmarski, Marie Fanelli
Zonderman, Alan B.
TI HEALTHY AGING IN NEIGHBORHOODS OF DIVERSITY ACROSS THE LIFE SPAN
(HANDLS): OVERCOMING BARRIERS TO IMPLEMENTING A LONGITUDINAL,
EPIDEMIOLOGIC, URBAN STUDY OF HEALTH, RACE, AND SOCIOECONOMIC STATUS
SO ETHNICITY & DISEASE
LA English
DT Article
DE Healthcare Disparities; Socioeconomic Status; Population Groups;
Epidemiologic Research Design; Health Surveys; Longitudinal Studies
ID CANCER CLINICAL-TRIALS; HEART-RATE-VARIABILITY; MULTIPLE-PASS METHOD;
AFRICAN-AMERICANS; UNDERREPRESENTED POPULATIONS; BLOOD-PRESSURE;
RECRUITMENT; COMMUNITY; CARE; DISCRIMINATION
AB Objective: Examine the influences of race, socioeconomic status, sex, and age on barriers to participation in a study of cross-sectional differences and longitudinal changes in health-related outcomes.
Methods: We designed a multidisciplinary, community-based, prospective longitudinal epidemiologic study among socioeconomically diverse African Americans and Whites. We recruited 3722 participants from Baltimore, Md. with a mean age of 47.7 (range 30-64) years, 45% males; 2200 African Americans (59%) and 1522 whites (41%); 41% reported household incomes below the 125% poverty delimiter.
Results: There were no significant age differences associated with sex or race. Participants below the 125% poverty delimiter were slightly younger than those above the delimiter. Age, race, and sex, but not poverty status, were associated with the likelihood of a physical examination. Older participants, women, and Whites were more likely to complete their examinations. Among those who completed their examinations, there were no age differences associated with sex and poverty status, but African Americans were negligibly younger than Whites.
Conclusions: Although some literature suggests that minorities and low-income people are less willing to participate in clinical research, these baseline data suggest that African Americans individuals and individuals from households with incomes below 125% of the poverty level are at least as willing to participate in observational clinical studies as Whites and higher income individuals of similar age and sex. (Ethn Dis. 2010;20:267-275)
C1 [Evans, Michele K.] NIA, Intramural Res Program, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA.
[Lepkowski, James M.] Univ Michigan, Inst Social Res, Ann Arbor, MI USA.
[Powe, Neil R.] Univ Calif San Francisco, Baltimore, MD USA.
[LaVeist, Thomas] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Kuczmarski, Marie Fanelli] Univ Delaware, Dept Nutr, Newark, DE USA.
RP Evans, MK (reprint author), NIA, Intramural Res Program, Biomed Res Ctr, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM evansmi@grc.nia.nih.gov
OI Zonderman, Alan B/0000-0002-6523-4778
FU NIH Office of the Director; Office of Behavioral and Social Sciences
Research
FX We acknowledge the visionary support and guidance from Dr. Dan Longo and
we thank Mr. Donald Bortner for his indispensable assistance in
designing and procuring our medical research vehicles. We recognize
support from the NIH Office of the Director, which provided start-up
funds. We also recognize the consistent support of the then NIH Office
on Minority Health and the current National Center on Minority Health
and Health Disparities. The study also was supported through the Office
of Behavioral and Social Sciences Research. We thank LifeLine
Technologies of Cincinnati who fabricated the medical research vehicles
and who have provided conscientious and skilled support since their
deployment. We thank all members of the HANDLS staff past and present
for their dedication to the goals and objectives of the study and their
excellent execution of the protocol.
NR 66
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U1 1
U2 14
PU INT SOC HYPERTENSION BLACKS-ISHIB
PI ATLANTA
PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA
SN 1049-510X
J9 ETHNIC DIS
JI Ethn. Dis.
PD SUM
PY 2010
VL 20
IS 3
BP 267
EP 275
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 645WP
UT WOS:000281497200010
PM 20828101
ER
PT J
AU Mackay, HJ
Hirte, H
Colgan, T
Covens, A
MacAlpine, K
Grenci, P
Wang, LS
Mason, J
Pham, PA
Tsao, MS
Pan, J
Zwiebel, J
Oza, AM
AF Mackay, Helen J.
Hirte, Hal
Colgan, Terrence
Covens, Al
MacAlpine, Katrina
Grenci, Pamela
Wang, Lisa
Mason, Jaqueline
Pham, Pnu-An
Tsao, Ming-S.
Pan, James
Zwiebel, James
Oza, Amit M.
TI Phase II trial of the histone deacetylase inhibitor belinostat in women
with platinum resistant epithelial ovarian cancer and micropapillary
(LMP) ovarian tumours
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Article
DE Micropapillary (LMP) ovarian tumours; Platinum resistant ovarian cancer;
Belinostat; Phase II
ID BORDERLINE TUMORS; SOLID TUMORS; SEROUS TUMORS; FOLLOW-UP; RECURRENT;
VORINOSTAT; GUIDELINES; CARCINOMA; EVALUATE; PXD101
AB Aim: Micropapillary/borderline (LMP) ovarian tumours are rarely included in clinical trials and are intrinsically resistant to radiation and chemotherapy. Platinum resistant epithelial ovarian cancer (EOC) has a poor prognosis. The histone deacetylase inhibitor belinostat demonstrated antitumour activity in pre-clinical ovarian cancer models.
Methods: A phase II study was performed to evaluate the activity of belinostat in two patient populations: women with metastatic or recurrent platinum resistant (progression within 6 months) EOC and LMP ovarian tumours, both groups had received no more than 3 prior lines of chemotherapy. Belinostat 1000 mg/m(2)/d was administered iv days 1-5 of a 21 d cycle. Peripheral blood mononuclear cells (PBMCs) and tumour biopsies, where possible, for correlative studies were obtained prior to and following treatment.
Results: Eighteen patients with EOC and 14 patients with LMP tumours were enrolled on study. Belinostat was well tolerated with no grade four toxicity (179 cycles). Grade 3 toxicity consisted of thrombosis (3 patients), hypersensitivity (1) and elevated ALP (1). One patient with LMP tumour had a partial response (unconfirmed) and 10 had stable disease (SD), 3 were non-evaluable. Median progression-free survival (PFS) was 13.4 months (95% confidence interval (CI), 5.6 - not reached). Best response in patients with EOC was SD (nine patients) and median PFS was 2.3 months (95% CI, 1.2-5.7 months). An accumulation of acetylated histones H3 and H4 was noted in PBMCs and in tumour tissue.
Conclusions: Belinostat is well tolerated in both patient groups and shows some activity in patients with micropapillary (LMP) disease. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Mackay, Helen J.; Hirte, Hal; Covens, Al; MacAlpine, Katrina; Grenci, Pamela; Wang, Lisa; Mason, Jaqueline; Pham, Pnu-An; Tsao, Ming-S.; Pan, James; Oza, Amit M.] Princess Margaret Phase II Consortium, Toronto, ON, Canada.
[Colgan, Terrence] Sunnybrook Reg Canc Ctr, Toronto, ON, Canada.
[Zwiebel, James] NCI, Rockville, MD USA.
RP Mackay, HJ (reprint author), Princess Margaret Hosp, 610 Univ Ave, Toronto, ON M5G 2M9, Canada.
EM helen.mackay@uhn.on.ca
RI Colgan, Terence/J-2339-2016
FU [N01-CM-62203]
FX Support: This trial was supported by funding from N01-CM-62203 and drug
was supplied by the Cancer Therapeutics Evaluation Program, US National
Cancer Institute and the Campbell Family Institute.
NR 30
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U1 0
U2 4
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 JUN
PY 2010
VL 46
IS 9
BP 1573
EP 1579
DI 10.1016/j.ejca.2010.02.047
PG 7
WC Oncology
SC Oncology
GA 618WV
UT WOS:000279387700020
PM 20304628
ER
PT J
AU Makler, O
Oved, K
Netzer, N
Wolf, D
Reiter, Y
AF Makler, Oryan
Oved, Kfir
Netzer, Nir
Wolf, Dana
Reiter, Yoram
TI Direct visualization of the dynamics of antigen presentation in human
cells infected with cytomegalovirus revealed by antibodies mimicking TCR
specificity
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
DE Ab; Ag presentation/processing; MHC; Virology
ID MHC CLASS-I; HUMAN RECOMBINANT ANTIBODIES; COMPLEX-RESTRICTED
SPECIFICITY; T-CELLS; IMMUNE EVASION; HEAVY-CHAINS;
ENDOPLASMIC-RETICULUM; PHENOTYPIC ANALYSIS; SITU DETECTION;
GOLGI-COMPLEX
AB There are no direct means to study class I MHC presentation in human normal or diseased cells. Using CMV-infected human cells and applying novel mAb that mimic T-cell receptor specificity directed toward the immunogenic epitope of the viral pp65 protein presented on HLA-A2 molecules, we directly imaged the dynamics of Ag presentation in infected cells. We demonstrate that following infection large intracellular pools of HLA-A2/pp65 complexes are localized to the Golgi. These HLA-A2/pp65 pools account for the majority of total HLA-A2 molecules in infected cells. Interestingly, these large pools are sequestered inside infected cells and only a small portion of them are exported to the cell surface. Virus-induced class I MHC down-regulation did not affect the intracellular pool of HLA-A2/pp65 complexes. Our data also suggest that proteasome function influences the release of class I complexes to the membrane. We present herein a new and direct molecular tool to study the dynamics of viral Ag presentation that may further elucidate the balance between immune response versus viral escape.
C1 [Makler, Oryan; Oved, Kfir; Reiter, Yoram] Technion Israel Inst Technol, Fac Biol, IL-32000 Haifa, Israel.
[Netzer, Nir] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
[Wolf, Dana] Hadassah Univ Hosp, Dept Clin Microbiol & Infect Dis, IL-91120 Jerusalem, Israel.
RP Reiter, Y (reprint author), Technion Israel Inst Technol, Fac Biol, IL-32000 Haifa, Israel.
EM reiter@bc.technion.ac.il
FU Israel Science Foundation
FX This work was funded in part by a grant from the Israel Science
Foundation.
NR 44
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U1 2
U2 3
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY
SN 0014-2980
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD JUN
PY 2010
VL 40
IS 6
BP 1552
EP 1565
DI 10.1002/eji.200939875
PG 14
WC Immunology
SC Immunology
GA 614RK
UT WOS:000279077200006
PM 20306470
ER
PT J
AU Caminiti, R
Chafee, MV
Battaglia-Mayer, A
Averbeck, BB
Crowe, DA
Georgopoulos, AP
AF Caminiti, Roberto
Chafee, Matthew V.
Battaglia-Mayer, Alexandra
Averbeck, Bruno B.
Crowe, David A.
Georgopoulos, Apostolos P.
TI Understanding the parietal lobe syndrome from a neurophysiological and
evolutionary perspective
SO EUROPEAN JOURNAL OF NEUROSCIENCE
LA English
DT Article; Proceedings Paper
CT 7th Forum of the Federation-of-European-Neuroscience-Societies (FENS)
CY JUL 03-07, 2010
CL Amsterdam, NETHERLANDS
SP Federat European Neurosci Soc
DE behavioral neurophysiology; evolution; neuroanatomy; neuropsychology;
parietal syndrome
ID LATERAL INTRAPARIETAL AREA; UNILATERAL SPATIAL NEGLECT; DORSOLATERAL
PREFRONTAL CORTEX; EYE-HAND COORDINATION; CHIMPANZEES PAN-TROGLODYTES;
MULTIPLE-STIMULUS DISPLAYS; SELECTIVE VISUAL-ATTENTION; MOTOR INTENTION
ACTIVITY; LIGHT-SENSITIVE NEURONS; MACAQUE MONKEY
AB In human and nonhuman primates parietal cortex is formed by a multiplicity of areas. For those of the superior parietal lobule (SPL) there exists a certain homology between man and macaques. As a consequence, optic ataxia, a disturbed visual control of hand reaching, has similar features in man and monkeys. Establishing such correspondence has proven difficult for the areas of the inferior parietal lobule (IPL). This difficulty depends on many factors. First, no physiological information is available in man on the dynamic properties of cells in the IPL. Second, the number of IPL areas identified in the monkey is paradoxically higher than that so far described in man, although this issue will probably be reconsidered in future years, thanks to comparative imaging studies. Third, the consequences of parietal lesions in monkeys do not always match those observed in humans. This is another paradox if one considers that, in certain cases, the functional properties of neurons in the monkey's IPL would predict the presence of behavioral skills, such as construction capacity, that however do not seem to emerge in the wild. Therefore, constructional apraxia, which is well characterized in man, has never been described in monkeys and apes. Finally, only certain aspects, i.e. hand directional hypokinesia and gaze apraxia (Balint's psychic paralysis of gaze), of the multifaceted syndrome hemispatial neglect have been described in monkeys. These similarities, differences and paradoxes, among many others, make the study of the evolution and function of parietal cortex a challenging case.
C1 [Caminiti, Roberto; Battaglia-Mayer, Alexandra] Univ Roma La Sapienza, Dept Physiol & Pharmacol, I-00185 Rome, Italy.
[Chafee, Matthew V.; Crowe, David A.; Georgopoulos, Apostolos P.] Univ Minnesota, Dept Neurosci, Minneapolis, MN USA.
[Chafee, Matthew V.; Crowe, David A.; Georgopoulos, Apostolos P.] VA Med Ctr, Brain Sci Ctr, Minneapolis, MN USA.
[Averbeck, Bruno B.] NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA.
RP Caminiti, R (reprint author), Univ Roma La Sapienza, Dept Physiol & Pharmacol, Piazzale Aldo Moro 5, I-00185 Rome, Italy.
EM roberto.caminiti@uniroma1.it
RI Battaglia-Mayer, Alexandra/B-3749-2010
FU Intramural NIH HHS [Z99 MH999999]
NR 219
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U1 3
U2 17
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 JUN
PY 2010
VL 31
IS 12
SI SI
BP 2320
EP 2340
DI 10.1111/j.1460-9568.2010.07291.x
PG 21
WC Neurosciences
SC Neurosciences & Neurology
GA 613YP
UT WOS:000279021600018
PM 20550568
ER
PT J
AU Kumar, V
Talisman, IJ
Malhotra, SV
AF Kumar, Vineet
Talisman, Ian Jamie
Malhotra, Sanjay V.
TI Application of Halide Molten Salts as Novel Reaction Media for
O-Glycosidic Bond Formation
SO EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
LA English
DT Article
DE O-Glycosidation; Molten salts; Ionic liquids; Carbohydrates;
Koenigs-Knorr reaction
ID BETA-D-GLUCOPYRANOSIDES; TRANSFER-CATALYZED SYNTHESIS; CHIRAL IONIC
LIQUIDS; SYNTHETIC PENTASACCHARIDE; SELECTIVE BENZOYLATION;
ANTITHROMBOTIC AGENTS; ANTIVIRAL DRUGS; PROTIC ACID; FACTOR XA;
NUCLEOSIDES
AB In this study we have explored the application of halide molten salts as reaction media for O-glycosidic bond formation under basic conditions and mild heating. Eighteen different room-temperature ionic liquids and molten salts, representing four different classes of cations (i.e. imidazolium, pyridinium, pyrrolidinium and ammonium), were screened in the glycosidation reaction of p-nitrophenol with aceto-bromo-alpha-D-galactose. 1-Butyl-4-methylimidazolium chloride (BMIM center dot Cl) gave the best results and was applied in the reactions of other phenolic substrates to give the products with up to 80% yields. All the reactions were highly selective to give the beta-anomers, and the molten salt BMIM center dot Cl could easily be reused with no apparent loss in activity.
C1 [Kumar, Vineet; Talisman, Ian Jamie; Malhotra, Sanjay V.] NCI, Lab Synthet Chem, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Malhotra, SV (reprint author), NCI, Lab Synthet Chem, SAIC Frederick Inc, 1050 Boyles St, Frederick, MD 21702 USA.
EM malhotrasa@mail.nih.gov
FU NCI, National Institutes of Health [HSN261200800001E]
FX The authors would like to thank the National Cancer Institute (NCI)
Developmental Therapeutics Program. This project has been funded in
whole or in part with federal funds from the NCI, National Institutes of
Health under Contract No. HSN261200800001E. 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 46
TC 8
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U1 3
U2 10
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1434-193X
J9 EUR J ORG CHEM
JI Eur. J. Org. Chem.
PD JUN
PY 2010
IS 18
BP 3377
EP 3381
DI 10.1002/ejoc.201000188
PG 5
WC Chemistry, Organic
SC Chemistry
GA 623MY
UT WOS:000279746300002
ER
PT J
AU Heishman, SJ
Lee, DC
Taylor, RC
Singleton, EG
AF Heishman, Stephen J.
Lee, Dustin C.
Taylor, Richard C.
Singleton, Edward G.
TI Prolonged Duration of Craving, Mood, and Autonomic Responses Elicited by
Cues and Imagery in Smokers: Effects of Tobacco Deprivation and Sex
SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY
LA English
DT Article
DE tobacco craving; cue-reactivity; in vivo cues; imagery; time course; sex
differences
AB Increases in self-reported craving and changes in autonomic functioning are reliably elicited when smokers are exposed to tobacco-related stimuli compared with neutral stimuli. However, few studies have reported the time course of cue-elicited craving or have directly compared the effectiveness of smoking cues versus imagery to evoke a craving response. In addition to these two issues, we investigated the influence of tobacco deprivation and sex on craving, mood, and autonomic responses. Sixty cigarette smokers (30 men, 30 women) were tested in two counterbalanced sessions, one after overnight tobacco deprivation and one during ad libitum smoking. At each session, participants were exposed to four randomized experimental trials: smoking imagery, neutral imagery, smoking cues, and neutral cues. Tobacco craving and mood were assessed repeatedly and physiological measures were recorded continuously for 30 min after imagery or cue exposure. Compared with neutral trials, smoking cues and smoking imagery reliably increased tobacco craving, negative mood, heart rate, and blood pressure and decreased positive mood ratings. Changes were observed immediately after cue and imagery presentation and remained unchanged for 30 min. Responding was greater in the nondeprived condition, and cues elicited more robust responding than imagery for most measures. Women responded more robustly to smoking cues only in the nondeprived condition, whereas imagery evoked greater responses in men during both conditions. These findings provide new data on the time course, magnitude, and tobacco deprivation effects on elicited craving. Sex differences were dependent on stimulus type and deprivation condition.
C1 [Heishman, Stephen J.] NIDA, Nicotine Psychopharmacol Sect, Intramural Res Program, Baltimore, MD 21224 USA.
RP Heishman, SJ (reprint author), NIDA, Nicotine Psychopharmacol Sect, Intramural Res Program, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM heishman@nih.gov
OI Lee, Dustin/0000-0002-4818-9733; Singleton, Edward
G./0000-0003-3442-877X
FU National Institutes of Health, National Institute on Drug Abuse
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute on Drug Abuse. We
thank Heather Andes, Janeen Nichels, John Etter, and Rebecca Evans for
their technical assistance in conducting the study.
NR 61
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U1 1
U2 4
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 1064-1297
J9 EXP CLIN PSYCHOPHARM
JI Exp. Clin. Psychopharmacol.
PD JUN
PY 2010
VL 18
IS 3
BP 245
EP 256
DI 10.1037/a0019401
PG 12
WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy;
Psychiatry
SC Psychology; Pharmacology & Pharmacy; Psychiatry
GA 610KF
UT WOS:000278730800006
PM 20545389
ER
PT J
AU Mizelle, JC
Forrester, L
Hallett, M
Wheaton, LA
AF Mizelle, J. C.
Forrester, Larry
Hallett, Mark
Wheaton, Lewis A.
TI Electroencephalographic reactivity to unimodal and bimodal visual and
proprioceptive demands in sensorimotor integration
SO EXPERIMENTAL BRAIN RESEARCH
LA English
DT Article
DE EEG; Motor control; Sensorimotor integration
ID MOVEMENT-RELATED POTENTIALS; ANTERIOR CINGULATE CORTEX; EVENT-RELATED
POTENTIALS; PREMOTOR CORTEX; MOTOR CORTEX; REACHING MOVEMENTS; FINGER
MOVEMENT; LOWER-EXTREMITY; WORKING-MEMORY; EEG
AB We used electroencephalography to see how the brain deals with altered sensory processing demands in lower extremity movements. In unimodal conditions, sensory processing demands were altered with subjects performing movement to a small or large visual target, or with a small or large weight to modify proprioception. In bimodal conditions, both weight and targets needed to be met. We assessed activity over primary sensorimotor, premotor and parietal areas before and during knee movements. In unimodal conditions, the primary sensorimotor area showed the least sensitivity to the maximally increased sensory demand in both vision and proprioception, while the premotor region was most sensitive to proprioceptive demands, and the parietal region showed greatest sensitivity to visual demands. In bimodal conditions, intermediate levels of sensory processing demand maximally increased activation at premotor and parietal regions. However, when visual and proprioceptive demands were both maximal, activation decreased and was similar to that seen with the lowest level of sensory processing demand. As behavior was consistent across conditions while activation at these regions decreased, we suggest that additional brain areas, possibly high order cognitive and attentional regions, may be required to augment the function of the traditional sensorimotor network in lower extremity movements with increasingly difficult sensory processing demands.
C1 [Mizelle, J. C.; Wheaton, Lewis A.] Georgia Inst Technol, Sch Appl Physiol, Atlanta, GA 30332 USA.
[Mizelle, J. C.; Forrester, Larry] Baltimore Dept Vet Affairs, Baltimore, MD USA.
[Mizelle, J. C.; Forrester, Larry; Wheaton, Lewis A.] Univ Maryland, Sch Med, Dept Phys Therapy & Rehabil Sci, Baltimore, MD 21201 USA.
[Forrester, Larry] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA.
[Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
RP Wheaton, LA (reprint author), Georgia Inst Technol, Sch Appl Physiol, 281 Ferst Dr,Room 104, Atlanta, GA 30332 USA.
EM lewis.wheaton@ap.gatech.edu
RI Wheaton, Lewis /B-4482-2009
OI Wheaton, Lewis /0000-0003-0771-0294
FU Veterans Affairs [B3688R]; National Institutes of Health National Center
[T32-HD041899-01A1]; Veterans Affairs Rehabilitation Research and
Development [B3390 K]; Baltimore Veterans Affairs Geriatrics Research,
Education, and Clinical Center; NINDS
FX This study was supported by the Veterans Affairs 2008 Pre-Doctoral
Associated Health Rehabilitation Research Fellowship Program; National
Institutes of Health National Center for Medical Rehabilitation Research
T32 Award (#T32-HD041899-01A1); Veterans Affairs Center for Excellence
in Exercise and Robotics for Neurological Disorders (COE# B3688R);
Veterans Affairs Stroke Research Enhancement Award Program; Veterans
Affairs Rehabilitation Research and Development, Advanced Research
Career Development Award (B3390 K); Baltimore Veterans Affairs
Geriatrics Research, Education, and Clinical Center. Dr. Hallett is
supported by the NINDS Intramural Research Program.
NR 55
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U1 1
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0014-4819
J9 EXP BRAIN RES
JI Exp. Brain Res.
PD JUN
PY 2010
VL 203
IS 4
BP 659
EP 670
DI 10.1007/s00221-010-2273-8
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 605LF
UT WOS:000278348400003
PM 20445965
ER
PT J
AU Korangy, F
Hochst, B
Manns, MP
Greten, TF
AF Korangy, Firouzeh
Hoechst, Bastian
Manns, Michael P.
Greten, Tim F.
TI Immunotherapy of hepatocellular carcinoma
SO EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY
LA English
DT Review
DE cancer vaccine; dendritic cell; immune suppressor mechanism;
immunotherapy; myeloid-derived suppressor cell; regulatory T cell; tumor
antigen
ID T-CELL RESPONSES; ENDOTHELIAL GROWTH-FACTOR; MYELOID SUPPRESSOR-CELLS;
HEPATITIS-B-VIRUS; TELOMERASE REVERSE-TRANSCRIPTASE; RADIOFREQUENCY
THERMAL ABLATION; COLONY-STIMULATING FACTOR; ANTIGEN-PRESENTING CELLS;
HUMAN ALPHA-FETOPROTEIN; DENDRITIC CELLS
AB Hepatocellular carcinoma (HCC) represents the third most common cause of cancer-related death worldwide and efficient treatment options are urgently needed. Based on its pathogenesis, in addition to a number of correlative studies, immunotherapy represents a potential therapeutic option for patients with HCC. However, tumors have also evolved numerous immune escape mechanisms, including the generation of cells with immune suppressor functions, such as Tregs and myeloid-derived suppressor cells. It has been shown that these suppressor cells mask tumor-specific immune responses in patients with HCC. Different immunotherapeutic approaches including peptide- and dendritic cell-based therapies have demonstrated promising results in patients with HCC. However, we propose that any of these immunotherapeutic approaches needs to be combined with a therapy specifically targeting suppressor cells in HCC.
C1 [Korangy, Firouzeh; Hoechst, Bastian; Manns, Michael P.; Greten, Tim F.] Hannover Med Sch, D-3000 Hannover, Germany.
[Korangy, Firouzeh; Hoechst, Bastian; Greten, Tim F.] Hannover Med Sch, Twincore Ctr Expt & Clin Res, D-30625 Hannover, Germany.
RP Greten, TF (reprint author), NCI, Med Oncol Branch, NIH, Bldg 10,Rm 12N226,900 Rockville Pike, Rockville, MD USA.
EM tim.greten@nih.gov
RI Greten, Tim/B-3127-2015
OI Greten, Tim/0000-0002-0806-2535
FU Deutsche Forschungsgemeinschaft (DFG) [KFO119]; Helmholtz Association
within Helmholtz Alliance on Immunotherapy of Cancer
FX This work was supported by grants from the Deutsche
Forschungsgemeinschaft (DFG; KFO119) and by the Initiative and
Networking Fund of the Helmholtz Association within the Helmholtz
Alliance on Immunotherapy of Cancer. 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 111
TC 13
Z9 16
U1 0
U2 8
PU EXPERT REVIEWS
PI LONDON
PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB,
ENGLAND
SN 1747-4124
J9 EXPERT REV GASTROENT
JI Expert Rev. Gastroenterol. Hepatol.
PD JUN
PY 2010
VL 4
IS 3
BP 345
EP 353
DI 10.1586/EGH.10.18
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 860XU
UT WOS:000297982600017
PM 20528121
ER
PT J
AU Apostolopoulos, V
Marincola, FM
AF Apostolopoulos, Vasso
Marincola, Francesco M.
TI Methods to measure vaccine immunity Foreword
SO EXPERT REVIEW OF VACCINES
LA English
DT Editorial Material
C1 [Apostolopoulos, Vasso] Burnet Inst, Ctr Immunol, Immunol & Vaccine Lab, Melbourne, Vic 3004, Australia.
[Marincola, Francesco M.] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Marincola, Francesco M.] NIH, Trans NIH Ctr Human Immunol, Bethesda, MD 20892 USA.
RP Apostolopoulos, V (reprint author), Burnet Inst, Ctr Immunol, Immunol & Vaccine Lab, 85 Commercial Rd, Melbourne, Vic 3004, Australia.
EM vasso@burnet.edu.au
FU Intramural NIH HHS [ZIA CL002118-03]
NR 9
TC 1
Z9 1
U1 1
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 JUN
PY 2010
VL 9
IS 6
BP 545
EP 546
DI 10.1586/ERV.10.61
PG 2
WC Immunology
SC Immunology
GA 618CO
UT WOS:000279329200001
PM 20518709
ER
PT J
AU Bedognetti, D
Wang, E
Sertoli, MR
Marincola, FM
AF Bedognetti, Davide
Wang, Ena
Sertoli, Mario Roberto
Marincola, Francesco M.
TI Gene-expression profiling in vaccine therapy and immunotherapy for
cancer
SO EXPERT REVIEW OF VACCINES
LA English
DT Review
DE cancer immunotherapy; gene expression; immunologic constant; melanoma;
microarray; tumor rejection; vaccine therapy
ID METASTATIC MELANOMA PATIENTS; VERSUS-HOST-DISEASE; C VIRUS-INFECTION;
ALLOGRAFT-REJECTION; COLORECTAL-CANCER; IMMUNE-RESPONSES; HEPATITIS-C;
T-CELLS; IMMUNOLOGICAL CONSTANT; TRANSCRIPTION FACTORS
AB The identification of tumor antigens recognized by T cells led to the design of therapeutic strategies aimed at eliciting adaptive immune responses. The last decade of experience has shown that, although active immunization can induce enhancement of anticancer T-cell precursors (easily detectable in standard assays), most often they are unable to induce tumor regression and, consequently, have scarcely any impact on overall survival. Moreover, in the few occasions when tumor rejection occurs, the mechanisms determining this phenomenon remain poorly understood, and data derived from in vivo human observations are rare. The advent of high-throughput gene-expression analysis (microarrays) has cast new light on unrecognized mechanisms that are now deemed to be central for the development of efficient immune-mediated tumor rejection. The aim of this article is to review the data on the molecular signature associated with this process. We believe that the description of how the mechanism of immune-mediated tissue destruction occurs would contribute to our understanding of why it happens, thereby allowing us to develop more effective immune therapeutic strategies.
C1 [Bedognetti, Davide; Wang, Ena; Marincola, Francesco M.] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Bedognetti, Davide; Wang, Ena; Marincola, Francesco M.] NIH, Trans NIH Ctr Human Immunol, Bethesda, MD 20892 USA.
[Bedognetti, Davide; Sertoli, Mario Roberto] Natl Inst Canc Res, Dept Med Oncol, SC Oncol Med B, Genoa, Italy.
[Bedognetti, Davide] Univ Genoa, Dept Internal Med, I-16126 Genoa, Italy.
[Bedognetti, Davide; Sertoli, Mario Roberto] Univ Genoa, Dept Oncol Biol & Genet, Genoa, Italy.
RP Marincola, FM (reprint author), NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM fmarincola@cc.nih.gov
RI Bedognetti, Davide/A-9090-2012;
OI Bedognetti, Davide/0000-0002-5857-773X
FU Fondazione Associazione Italiana di Oncologia Medica (AIOM); University
of Genoa
FX Davide Bedognetti thanks Fondazione Associazione Italiana di Oncologia
Medica (AIOM) and the University of Genoa for supporting his
scholarship; Laura Miano, Tatiana Bricco, Valentina Careri and Lucia
Rizzo (University of Genoa) for their outstanding administrative service
and Francesco Boccardo (National Cancer Research Institute and
University of Genoa) for his teaching.
NR 102
TC 40
Z9 42
U1 0
U2 4
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 JUN
PY 2010
VL 9
IS 6
BP 555
EP 565
DI 10.1586/ERV.10.55
PG 11
WC Immunology
SC Immunology
GA 618CO
UT WOS:000279329200007
PM 20518712
ER
PT J
AU Burbelo, PD
Ching, KH
Bush, ER
Han, BL
Iadarola, MJ
AF Burbelo, Peter D.
Ching, Kathryn H.
Bush, Emily R.
Han, Brian L.
Iadarola, Michael J.
TI Antibody-profiling technologies for studying humoral responses to
infectious agents
SO EXPERT REVIEW OF VACCINES
LA English
DT Review
DE antibody-profiling technologies; antigen array; luciferase
immunoprecipitation systems; vaccine targets
ID LUCIFERASE IMMUNOPRECIPITATION SYSTEMS; LINKED-IMMUNOSORBENT-ASSAY;
PROTEIN MICROARRAY; NEUTRALIZING EPITOPES; SEROLOGICAL DETECTION;
ONCHOCERCA-VOLVULUS; 4-ANTIGEN MIXTURE; KAPOSIS-SARCOMA; ANTIGEN;
VACCINE
AB Analyses of humoral responses against different infectious agents are critical for infectious disease diagnostics, understanding pathogenic mechanisms, and the development and monitoring of vaccines. While ELISAs are often used to measure antibody responses to one or several targets, new antibody-profiling technologies, such as protein microarrays, can now evaluate antibody responses to hundreds, or even thousands, of recombinant antigens at one time. These large-scale studies have uncovered new antigenic targets, provided new insights into vaccine research and yielded an overview of immunoreactivity against almost the entire proteome of certain pathogens. However, solid-phase antigen arrays also have drawbacks that limit the type of information obtained, including suboptimal detection of conformational epitopes, high backgrounds due to impure antigens and a narrow dynamic range of detection. We have developed a solution-phase antibody-profiling technology, luciferase immunoprecipitation systems (LIPS), which harnesses light-emitting recombinant antigen fusion proteins to quantitatively measure patient antibody titers. Owing to the highly linear light output of the luciferase reporter, some antibodies can be detected without serum dilution in a dynamic range of detection often spanning seven orders of magnitude. When LIPS is applied iteratively with multiple target antigens, a high-definition antibody profile is obtained. Here, we discuss the application of these different antibody-profiling technologies and their associated limitations with particular emphasis on protein microarrays. We also describe LIPS in detail and discuss several clinically relevant uses of the technology. Together, these new technologies offer new tools for understanding humoral responses to known and emerging infectious agents.
C1 [Burbelo, Peter D.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA.
[Ching, Kathryn H.; Bush, Emily R.; Han, Brian L.; Iadarola, Michael J.] Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, NIH, Bethesda, MD 20892 USA.
RP Burbelo, PD (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Bldg 49,Room 1C20,49 Convent Dr, Bethesda, MD 20892 USA.
EM burbelop@nidcr.nih.gov
FU National Institute of Dental and Craniofacial Research, NIH
FX This work was supported by the intramural research program of the
National Institute of Dental and Craniofacial Research, NIH. Two of the
authors, Peter D Burbelo and Michael J Iadarola, have multiple patent
applications submitted using the LIPS technology. 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 54
TC 39
Z9 39
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 JUN
PY 2010
VL 9
IS 6
BP 567
EP 578
DI 10.1586/ERV.10.50
PG 12
WC Immunology
SC Immunology
GA 618CO
UT WOS:000279329200008
PM 20518713
ER
PT J
AU Zaritskaya, L
Shurin, MR
Sayers, TJ
Malyguine, AM
AF Zaritskaya, Liubov
Shurin, Michael R.
Sayers, Thomas J.
Malyguine, Anatoli M.
TI New flow cytometric assays for monitoring cell-mediated cytotoxicity
SO EXPERT REVIEW OF VACCINES
LA English
DT Review
DE cell-mediated cytotoxicity; cytotoxic T lymphocyte; multiparameter flow
cytometry; natural killer cell; vaccine
ID CD8(+) T-CELLS; NATURAL-KILLER-CELL; CANCER VACCINE TRIALS; LABELED
TARGET-CELLS; CLASS-I TETRAMERS; B ELISPOT ASSAY; LYMPHOCYTE ACTIVITY;
CHROMIUM-RELEASE; CYTO-TOXICITY; IMMUNE-RESPONSES
AB The exact immunologic responses after vaccination that result in effective antitumor immunity have not yet been fully elucidated and the data from ex vivo T-cell assays have not yet defined adequate surrogate markers for clinical efficacy. A more detailed knowledge of the specific immune responses that correlate with positive clinical outcomes should help to develop better or novel strategies to effectively activate the immune system against tumors. Furthermore, clinically relevant material is often limited and, thus, precludes the ability to perform multiple assays. The two main assays currently used to monitor lymphocyte-mediated cytoxicity in cancer patients are the (51)Cr-release assay and IFN-gamma ELISpot assay. The former has a number of disadvantages, including low sensitivity, poor labeling and high spontaneous release of isotope from some tumor target cells. Additional problems with the (51)Cr-release assay include difficulty in obtaining autologous tumor targets, and biohazard and disposal problems for the isotope. The ELISpot assays do not directly measure cytotoxic activity and are, therefore, a surrogate marker of cyotoxic capacity of effector T cells. Furthermore, they do not assess cytotoxicity mediated by the production of the TNF family of death ligands by the cytotoxic cells. Therefore, assays that allow for the simultaneous measurement of several parameters may be more advantageous for clinical monitoring. In this respect, multifactor flow cytometry-based assays are a valid addition to the currently available immunologic monitoring assays. Use of these assays will enable detection and enumeration of tumor-specific cytotoxic T lymphocytes and their specific effector functions and any correlations with clinical responses. Comprehensive, multifactor analysis of effector cell responses after vaccination may help to detect factors that determine the success or failure of a vaccine and its immunological potency.
C1 [Zaritskaya, Liubov; Malyguine, Anatoli M.] NCI, Appl & Dev Res Support Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Shurin, Michael R.] Univ Pittsburgh, Med Ctr, Dept Pathol, Pittsburgh, PA USA.
[Shurin, Michael R.] Univ Pittsburgh, Med Ctr, Dept Immunol, Pittsburgh, PA USA.
[Sayers, Thomas J.] NCI, Canc & Inflammat Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
RP Malyguine, AM (reprint author), NCI, Appl & Dev Res Support Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
EM malyguinea@mail.nih.gov
RI Sayers, Thomas/G-4859-2015
FU National Cancer Institute, NIH [HHSN261200800001E]
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, NIH, under Contract No.
HHSN261200800001E. 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 136
TC 48
Z9 50
U1 1
U2 29
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 JUN
PY 2010
VL 9
IS 6
BP 601
EP 616
DI 10.1586/ERV.10.49
PG 16
WC Immunology
SC Immunology
GA 618CO
UT WOS:000279329200011
PM 20518716
ER
PT J
AU Reuschenbach, M
Kloor, M
Morak, M
Wentzensen, N
Germann, A
Garbe, Y
Tariverdian, M
Findeisen, P
Neumaier, M
Holinski-Feder, E
Doeberitz, MV
AF Reuschenbach, Miriam
Kloor, Matthias
Morak, Monika
Wentzensen, Nicolas
Germann, Anja
Garbe, Yvette
Tariverdian, Mirjam
Findeisen, Peter
Neumaier, Michael
Holinski-Feder, Elke
Doeberitz, Magnus von Knebel
TI Serum antibodies against frameshift peptides in microsatellite unstable
colorectal cancer patients with Lynch syndrome
SO FAMILIAL CANCER
LA English
DT Article
DE Antibodies; Frameshift peptides; Immune responses; Lynch syndrome;
Microsatellite instability
ID TUMOR-ASSOCIATED ANTIGENS; HUMORAL IMMUNE-RESPONSES; HNPCC MUTATION
CARRIERS; INDUCED NEOPEPTIDES; INSTABILITY; CARCINOMA; NY-ESO-1; COLON;
P53
AB High level microsatellite instability (MSI-H) occurs in about 15% of colorectal cancer (CRCs), either as sporadic cancers or in the context of hereditary non-polyposis cancer or Lynch syndrome. In MSI-H CRC, mismatch repair deficiency leads to insertion/deletion mutations at coding microsatellites and thus to the translation of frameshift peptides (FSPs). FSPs are potent inductors of T cell responses in vitro and in vivo. The present study aims at the identification of FSP-specific humoral immune responses in MSI-H CRC and Lynch syndrome. Sera from patients with history of MSI-H CRC (n = 69), healthy Lynch syndrome mutation carriers (n = 31) and healthy controls (n = 52) were analyzed for antibodies against FSPs using peptide ELISA. Reactivities were measured against FSPs derived from genes frequently mutated in MSI-H CRCs, AIM2, TGFBR2, CASP5, TAF1B, ZNF294, and MARCKS. Antibody reactivity against FSPs was significantly higher in MSI-H CRC patients than in healthy controls (P = 0.036, Mann-Whitney) and highest in patients with shortest interval between tumor resection and serum sampling. Humoral immune responses in patients were most frequently directed against FSPs derived from mutated TAF1B (11.6%, 8/69) and TGFBR2 (10.1%, 7/69). Low level FSP-specific antibodies were also detected in healthy mutation carriers. Our results show that antibody responses against FSPs are detectable in MSI-H CRC patients and healthy Lynch syndrome mutation carriers. Based on the high number of defined FSP antigens, measuring FSP-specific humoral immune responses is a highly promising tool for future diagnostic application in MSI-H cancer patients.
C1 [Reuschenbach, Miriam; Kloor, Matthias; Wentzensen, Nicolas; Germann, Anja; Garbe, Yvette; Doeberitz, Magnus von Knebel] Univ Heidelberg, Dept Appl Tumor Biol, Inst Pathol, D-69120 Heidelberg, Germany.
[Reuschenbach, Miriam; Kloor, Matthias; Wentzensen, Nicolas; Germann, Anja; Garbe, Yvette; Doeberitz, Magnus von Knebel] Univ Heidelberg Hosp, Grp Canc Early Detect, German Canc Res Ctr DKFZ Heidelberg, Heidelberg, Germany.
[Reuschenbach, Miriam; Kloor, Matthias; Wentzensen, Nicolas; Germann, Anja; Garbe, Yvette; Doeberitz, Magnus von Knebel] Univ Heidelberg Hosp, Mol Med Partnership Unit MMPU, Heidelberg, Germany.
[Morak, Monika; Holinski-Feder, Elke] Univ Munich, Med Genet Zentrum, Munich, Germany.
[Wentzensen, Nicolas] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MA USA.
[Tariverdian, Mirjam] Univ Heidelberg Hosp, Dept Surg, Heidelberg, Germany.
[Findeisen, Peter; Neumaier, Michael] Univ Hosp Mannheim, Inst Clin Chem, Mannheim, Germany.
RP Doeberitz, MV (reprint author), Univ Heidelberg, Dept Appl Tumor Biol, Inst Pathol, Neuenheimer Feld 220, D-69120 Heidelberg, Germany.
EM knebel@med.uni-heidelberg.de
RI von Knebel Doeberitz, Magnus/D-2372-2016
OI von Knebel Doeberitz, Magnus/0000-0002-0498-6781
FU "Deutsche Krebshilfe" [106908]
FX This work was funded by a grant from the "Deutsche Krebshilfe" (grant
number 106908).
NR 25
TC 20
Z9 21
U1 2
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1389-9600
J9 FAM CANCER
JI Fam. Cancer
PD JUN
PY 2010
VL 9
IS 2
BP 173
EP 179
DI 10.1007/s10689-009-9307-z
PG 7
WC Oncology; Genetics & Heredity
SC Oncology; Genetics & Heredity
GA 596VD
UT WOS:000277712700010
PM 19957108
ER
PT J
AU Hendrickson, WA
Xie, H
Le-Khac, M
Korkut, A
Ng, D
Courter, JR
Kwon, YD
Schon, A
Madani, N
LaLonde, JM
Chaiken, IM
Freire, E
Sodroski, J
Kwong, PD
Smith, AB
AF Hendrickson, W. A.
Xie, H.
Le-Khac, M.
Korkut, A.
Ng, D.
Courter, J. R.
Kwon, Y. D.
Schoen, A.
Madani, N.
LaLonde, J. M.
Chaiken, I. M.
Freire, E.
Sodroski, J.
Kwong, P. D.
Smith, A. B.
TI Ligand recognition and plasticity in HIV envelope glycoprotein gp120
SO FEBS JOURNAL
LA English
DT Meeting Abstract
CT 35th Congress of the Federation-of-European-Biochemical-Societies
CY JUN 26-JUL 01, 2010
CL Gothenburg, SWEDEN
C1 [Hendrickson, W. A.] Columbia Univ, Howard Hughes Med Inst, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
[Xie, H.; Le-Khac, M.] Columbia Univ, Dept Pharmacol, New York, NY USA.
[Ng, D.; Courter, J. R.; Smith, A. B.] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA.
[Kwon, Y. D.; Kwong, P. D.] Vaccine Res Ctr, NIH, Bethesda, MD USA.
[Schoen, A.; Freire, E.] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA.
[Madani, N.; Sodroski, J.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[LaLonde, J. M.] Bryn Mawr Coll, Dept Chem, Bryn Mawr, PA 19010 USA.
[Chaiken, I. M.] Drexel Univ, Coll Med, Dept Biochem & Mol Biol, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1742-464X
J9 FEBS J
JI FEBS J.
PD JUN
PY 2010
VL 277
SU 1
BP 15
EP 15
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 608EI
UT WOS:000278565100054
ER
PT J
AU Miri, K
Chang-Ro, L
Seung-Hyon, C
Hyun-Jin, K
Peterkofsky, A
Yeong-Jae, S
AF Miri, K.
Chang-Ro, L.
Seung-Hyon, C.
Hyun-Jin, K.
Peterkofsky, A.
Yeong-Jae, S.
TI Potassium mediates Escherichia coli enzyme IIANtriV dependent regulation
of sigma factor selectivity
SO FEBS JOURNAL
LA English
DT Meeting Abstract
CT 35th Congress of the Federation-of-European-Biochemical-Societies
CY JUN 26-JUL 01, 2010
CL Gothenburg, SWEDEN
C1 [Miri, K.; Chang-Ro, L.; Seung-Hyon, C.; Hyun-Jin, K.; Yeong-Jae, S.] Seoul Natl Univ, Inst Microbiol, Seoul, South Korea.
[Miri, K.; Chang-Ro, L.; Seung-Hyon, C.; Hyun-Jin, K.; Yeong-Jae, S.] Seoul Natl Univ, Dept Biol Sci, Seoul, South Korea.
[Peterkofsky, A.] NHLBI, NIH, Cell Biol Lab, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1742-464X
J9 FEBS J
JI FEBS J.
PD JUN
PY 2010
VL 277
SU 1
BP 161
EP 161
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 608EI
UT WOS:000278565100567
ER
PT J
AU Kim, HJ
Choe, MG
Lee, CR
Kim, M
Peterkofsky, A
Seok, YJ
Seok, YJ
AF Kim, H. -J.
Choe, M. G.
Lee, C. -R.
Kim, M.
Peterkofsky, A.
Seok, Y. -J.
Seok, Y. -J.
TI Dephosphorylated NPr of the nitrogen-metabolic PTS regulates lipid A
biosynthesis by direct interaction with LpxD
SO FEBS JOURNAL
LA English
DT Meeting Abstract
CT 35th Congress of the Federation-of-European-Biochemical-Societies
CY JUN 26-JUL 01, 2010
CL Gothenburg, SWEDEN
C1 [Kim, H. -J.; Choe, M. G.; Lee, C. -R.; Kim, M.; Seok, Y. -J.] Seoul Natl Univ, Inst Microbiol, Dept Biol Sci, Seoul, South Korea.
[Peterkofsky, A.] NHLBI, Cell Biol Lab, Natl Inst Hlth, Bethesda, MD USA.
[Seok, Y. -J.] Seoul Natl Univ, Dept Biophys & Chem Biol, Seoul, South Korea.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1742-464X
J9 FEBS J
JI FEBS J.
PD JUN
PY 2010
VL 277
SU 1
BP 178
EP 178
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 608EI
UT WOS:000278565100626
ER
PT J
AU Kumar, D
Abdulovic, AL
Viberg, J
Nilsson, AK
Kunkel, TA
Chabes, A
AF Kumar, D.
Abdulovic, A. L.
Viberg, J.
Nilsson, A. K.
Kunkel, T. A.
Chabes, A.
TI dNTP pool imbalances: Mechanism of mutagenesis and effects on cell cycle
SO FEBS JOURNAL
LA English
DT Meeting Abstract
CT 35th Congress of the Federation-of-European-Biochemical-Societies
CY JUN 26-JUL 01, 2010
CL Gothenburg, SWEDEN
C1 [Kumar, D.; Viberg, J.; Nilsson, A. K.; Chabes, A.] Umea Univ, Dept Med Biochem & Biophys, S-90187 Umea, Sweden.
[Abdulovic, A. L.; Kunkel, T. A.] NIEHS, NIH, Mol Genet Lab, Res Triangle Pk, NC 27709 USA.
[Abdulovic, A. L.; Kunkel, T. A.] DHHS, Struct Biol Lab, Res Triangle Pk, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1742-464X
J9 FEBS J
JI FEBS J.
PD JUN
PY 2010
VL 277
SU 1
BP 187
EP 187
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 608EI
UT WOS:000278565100658
ER
PT J
AU Wlodawer, A
Moulaei, T
Kurian, S
Thomas, C
Giomarelli, B
McMahon, J
Dauter, Z
O'Keefe, B
AF Wlodawer, A.
Moulaei, T.
Kurian, S.
Thomas, C.
Giomarelli, B.
McMahon, J.
Dauter, Z.
O'Keefe, B.
TI Monomerization of the viral entry inhibitor griffithsin yields insights
into the relationship between multivalent binding to high mannose
oligosaccharides and antiviral activity
SO FEBS JOURNAL
LA English
DT Meeting Abstract
CT 35th Congress of the Federation-of-European-Biochemical-Societies
CY JUN 26-JUL 01, 2010
CL Gothenburg, SWEDEN
C1 [Wlodawer, A.; Moulaei, T.; Kurian, S.; Thomas, C.; Giomarelli, B.; McMahon, J.; Dauter, Z.; O'Keefe, B.] Natl Canc Inst, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1742-464X
J9 FEBS J
JI FEBS J.
PD JUN
PY 2010
VL 277
SU 1
BP 249
EP 250
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 608EI
UT WOS:000278565100869
ER
PT J
AU Fujimoto, VY
Jain, T
Alvero, R
Nelson, LM
Catherino, WH
Olatinwo, M
Marsh, EE
Broomfield, D
Taylor, H
Armstrong, AY
AF Fujimoto, Victor Y.
Jain, Tarun
Alvero, Ruben
Nelson, Lawrence M.
Catherino, William H.
Olatinwo, Moshood
Marsh, Erica E.
Broomfield, Diana
Taylor, Herman
Armstrong, Alicia Y.
TI Proceedings from the Conference on Reproductive Problems in Women of
Color
SO FERTILITY AND STERILITY
LA English
DT Editorial Material
DE Women of color; reproductive health disparities; infertility access to
care; racial and ethnic disparities in IVF outcomes; leiomyomata
prevalence
ID IN-VITRO FERTILIZATION; NONTRADITIONAL RISK-FACTORS; HEART-STUDY
INVESTIGATORS; INFERTILITY SERVICES; AFRICAN-AMERICANS; UTERINE
LEIOMYOMA; ASIAN ETHNICITY; PREGNANCY RATES; UNITED-STATES; WHITE WOMEN
AB The purpose of the National Institutes of Health conference on Reproductive Problems in Women of Color that convened on July 25, 2009 was to bring investigators together to examine data related to reproductive health care access and ethnic disparities in reproductive problems, fertility treatments, and pregnancy outcomes. One of the goals discussed at this conference was to initiate a research network of investigators interested in studying these problems through the development of an American Society of Reproductive Medicine special interest group and Society of Assisted Reproductive Technology writing groups. (Fertil Steril (R) 2010; 94: 7-10. (C) 2010 by American Society for Reproductive Medicine.)
C1 [Fujimoto, Victor Y.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA.
[Jain, Tarun] Chicago IVF, Chicago, IL USA.
[Alvero, Ruben] Univ Colorado, Dept Obstet & Gynecol, Denver, CO 80202 USA.
[Nelson, Lawrence M.; Armstrong, Alicia Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD USA.
[Catherino, William H.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Olatinwo, Moshood] Univ S Alabama, Dept Obstet & Gynecol, Mobile, AL 36688 USA.
[Marsh, Erica E.] Northwestern Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA.
[Broomfield, Diana] Howard Univ, Dept Obstet & Gynecol, Washington, DC 20059 USA.
[Taylor, Herman] Univ Mississippi, Div Cardiovasc Dis & Internal Med, Jackson, MS 39216 USA.
RP Fujimoto, VY (reprint author), UCSF Ctr Reprod Hlth, 2356 Sutter St,7th Floor,J707, San Francisco, CA 94115 USA.
EM fujimotov@obgyn.ucsf.edu
FU Intramural NIH HHS [Z99 HD999999]
NR 56
TC 2
Z9 2
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
J9 FERTIL STERIL
JI Fertil. Steril.
PD JUN
PY 2010
VL 94
IS 1
BP 7
EP 10
DI 10.1016/j.fertnstert.2009.12.068
PG 4
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 611XM
UT WOS:000278858200002
PM 20171628
ER
PT J
AU Dorgan, JF
Spittle, CS
Egleston, BL
Shaw, CM
Kahle, LL
Brinton, LA
AF Dorgan, Joanne F.
Spittle, Cynthia S.
Egleston, Brian L.
Shaw, Christiana M.
Kahle, Lisa L.
Brinton, Louise A.
TI Assay reproducibility and within-person variation of Mullerian
inhibiting substance
SO FERTILITY AND STERILITY
LA English
DT Article
DE Mullerian inhibiting substance (MIS); antimullerian hormone (AMH); assay
reproducibility; coefficient of variation (CV); within-person variation;
intraclass correlation coefficient (ICC)
ID POLYCYSTIC-OVARY-SYNDROME; HORMONE SERUM CONCENTRATIONS; REPRODUCTIVE
AGE; MENSTRUAL-CYCLE; NORMAL WOMEN; DECLINE
AB Objectives: To assess reproducibility of a commercial mullerian inhibiting substance (MIS) assay and evaluate within-person variation in serum MIS levels.
Design: Assay reproducibility was evaluated by measuring MIS in multiple serum aliquots from the same blood collection. Within-person variation was assessed by measuring MIS in serum collected twice from the same individuals.
Setting: Cancer Prevention Biomarker and Genotyping Facility, fox Chase Cancer Center, Philadelphia, Pennsylvania.
Patient(s): Assay reproducibility was evaluated using serum from five volunteers with regular menstrual cycles. Within-person variation was evaluated in serum from 20 premenopausal women who donated blood twice at least 1 year apart.
Intervention(s): For both studies, samples were randomly ordered in batches and laboratory personnel were blinded to which aliquots were from the same subject.
Main Outcome Measure(s): The MIS was measured by ELISA.
Result(s): Within-and between-batch coefficients of variation (CVs) of the assay were 7.9% and 12.3%, respectively. After deleting one subject with extreme values, these CVs decreased to 7.6% and 7.7%, respectively. Within- and between-subject variance in MIS measurements were 2.19 and 0.31, respectively, and the intraclass correlation coefficient was 0.88 (95% confidence interval .77-.98).
Conclusion(s): The MIS serum concentration is relatively stable over 1 year in premenopausal women and can be measured with good reproducibility using a commercial kit. (Fertil Steril (R) 2010; 94: 301-4. (C) 2010 by American Society for Reproductive Medicine.)
C1 [Dorgan, Joanne F.; Egleston, Brian L.; Shaw, Christiana M.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Spittle, Cynthia S.] Wyeth Res, Collegeville, PA USA.
[Kahle, Lisa L.] Informat Management Serv Inc, Rockville, MD USA.
[Brinton, Louise A.] NCI, Rockville, MD USA.
RP Dorgan, JF (reprint author), Fox Chase Canc Ctr, 510 Township Line Rd, Cheltenham, PA 19012 USA.
EM joanne.dorgan@fccc.edu
RI Brinton, Louise/G-7486-2015
OI Brinton, Louise/0000-0003-3853-8562
FU National Institutes of Health [P30CA006927, P50CA083638]; National
Institutes of Health, Rockville, Maryland
FX Supported by National Institutes of Health grants P30CA006927 and
P50CA083638 to the Fox Chase Cancer Center, Philadelphia, Pennsylvania,
and by the National Institutes of Health intramural research program,
Rockville, Maryland.
NR 19
TC 9
Z9 9
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD JUN
PY 2010
VL 94
IS 1
BP 301
EP 304
DI 10.1016/j.fertnstert.2009.03.032
PG 4
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 611XM
UT WOS:000278858200050
PM 19409547
ER
PT J
AU Bell, DR
Clode, S
Fan, MQ
Fernandes, A
Foster, PMD
Jiang, T
Loizou, G
MacNicoll, A
Miller, BG
Rose, M
Tran, L
White, S
AF Bell, David R.
Clode, Sally
Fan, Ming Qi
Fernandes, Alwyn
Foster, Paul M. D.
Jiang, Tao
Loizou, George
MacNicoll, Alan
Miller, Brian G.
Rose, Martin
Tran, Lang
White, Shaun
TI Interpretation of studies on the developmental reproductive toxicology
of 2,3,7,8-tetrachlorodibenzo-p-dioxin in male offspring
SO FOOD AND CHEMICAL TOXICOLOGY
LA English
DT Review
DE Dioxin; TCDD; Developmental; Reproductive; Toxicity; Spermatogenesis
ID MALE WISTAR(HAN) RAT; LONG-EVANS RATS; LACTATIONAL EXPOSURE; IN-UTERO;
TISSUE CONCENTRATIONS; SUBCHRONIC EXPOSURE; ANDROGENIC STATUS; SPERM
NUMBERS; AH RECEPTOR; TCDD
AB There have been several studies on the maternal administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and effects in the reproductive tract of male offspring, subsequent to risk assessments undertaken in 2001. This review compares the methodology and results to examine key methodological features, and consistency in reported outcomes. Maternal dosing at >0.8 mu g TCDD/kg causes lethality and weight loss, and it is difficult to distinguish between direct and indirect effects of TCDD at these dose levels. Statistically significant effects of maternal doses of <1 mu g TCDD/kg (i.e. the dose levels relevant for risk assessment) on prostate weight or epididymal sperm counts in offspring were reported in the minority of studies. The pharmacokinetics of TCDD differs considerably between acute and chronic dosing, and with dose level of TCDD. On the basis of body burden, TCDD had different potency at inducing adverse effects in the only comparison study between acute and chronic dosing. Understanding of the pharmacokinetics of TCDD and relationship to adverse effects in offspring is required. These analyses identify key features of TCDD developmental toxicity in male offspring, and identify data needs for future risk assessment. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Bell, David R.] European Chem Agcy, Helsinki 00121, Finland.
[Bell, David R.; Fan, Ming Qi; Jiang, Tao] Univ Nottingham, Sch Biol, Nottingham NG7 2RD, England.
[Clode, Sally] Covance Labs Ltd, Harrogate HG3 1PY, N Yorkshire, England.
[Fernandes, Alwyn; MacNicoll, Alan; Rose, Martin; White, Shaun] Food & Environm Res Agcy, York YO41 1LZ, N Yorkshire, England.
[Foster, Paul M. D.] NIEHS, Res Triangle Pk, NC 27709 USA.
[Loizou, George] Hlth & Safety Lab, Buxton SK17 9JN, Derby, England.
[Miller, Brian G.; Tran, Lang] Inst Occupat Med, Edinburgh EH14 4AP, Midlothian, Scotland.
RP Bell, DR (reprint author), European Chem Agcy, POB 400, Helsinki 00121, Finland.
EM david.bell@echa.europa.eu
OI Rose, Martin/0000-0001-7071-180X
FU UK Food Standards Agency [T01034]; FERA; UK FSA; Dow Chemical Company
FX Practical studies on the toxicology and disposition of TCDD were funded
by a contract (T01034) from the UK Food Standards Agency. We thank
Declan Brady for excellent technical support. We thank the editor and
anonymous reviewers for constructive and insightful comments. D.R.B. is
in receipt of funding from FERA, the UK FSA and Dow Chemical Company,
for research on dioxins. DRB wishes to make clear that the opinions in
this paper were written in a personal capacity, and do not necessarily
reflect the position of ECHA.
NR 49
TC 14
Z9 14
U1 0
U2 9
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0278-6915
J9 FOOD CHEM TOXICOL
JI Food Chem. Toxicol.
PD JUN
PY 2010
VL 48
IS 6
BP 1439
EP 1447
DI 10.1016/j.fct.2010.04.005
PG 9
WC Food Science & Technology; Toxicology
SC Food Science & Technology; Toxicology
GA 610WB
UT WOS:000278768500002
PM 20388530
ER
PT J
AU Samuni, Y
Ishii, H
Hyodo, F
Samuni, U
Krishna, MC
Goldstein, S
Mitchell, JB
AF Samuni, Yuval
Ishii, Hisanari
Hyodo, Fuminori
Samuni, Uri
Krishna, Murali C.
Goldstein, Sara
Mitchell, James B.
TI Reactive oxygen species mediate hepatotoxicity induced by the Hsp90
inhibitor geldanamycin and its analogs
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Quinone; Semiquinone; Reduction potential; 17-AAG; 17-DMAG; hepatocytes;
Spin-trapping; Tempol; DMPO; EPR; Kinetics
ID NITRIC-OXIDE; ADVANCED MALIGNANCIES; OXOAMMONIUM CATION; DT-DIAPHORASE;
TOXICITY; SUPEROXIDE; PROTEIN; METABOLISM; REDUCTION; RELEVANCE
AB Geldanamycin (GM), a benzoquinone ansamycin antibiotic, is a natural product inhibitor of Hsp90 with potent and broad anti-cancer properties. Because of its adverse effects on liver, its less toxic derivatives 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) and 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG) are currently being evaluated for the treatment of cancer. Previously, it has been demonstrated that the redox cycling of GM by NADPH-cytochrome P450 reductase leads to the formation of the GM semiquinone and superoxide radicals, the latter being identified using spin-trapping. We hypothesized that the different hepatotoxicity induced by GM, 17-AAG and 17-DMAG reflects the redox active properties of the quinone moiety and possibly the extent of superoxide formation, which may stimulate cellular oxidative injury. Our data demonstrate that superoxide can be efficiently trapped during the reduction of GM, 17-AAG and 17-DMAG by NADPH-cytochrome P450 reductase, and that superoxide formation rate followed the order 17-DMAG > 17-AAG > GM. In the absence of superoxide scavengers, the rate of NADPH oxidation followed the order 17-DMAG > GM > 17-AAG. The half-wave one-electron reduction potentials (E(1/2)) of GM, 17-AAG and 17-DMAG in DMSO have been determined to be -0.37, -0.13 and -0.015 V (vs. Ag/AgCl), respectively. If the same order of E(1/2) follows in neutral aqueous media, thermodynamic considerations imply that 17-DMAG is more readily reduced by the P450 reductase as well as by superoxide. The order of the drug cytotoxicity toward rat primary hepatocytes, as determined by their effect on cell viability and on intracellular oxidant level, was opposite to the order of E(1/2) of the respective quinone/semiquinone couples. These results suggest that hepatotoxicity exhibited by the Hsp90 inhibitors belonging to benzoquinone ansamycins could be attributed to superoxide. The apparent discrepancy between the order of toxicity and the orders of superoxide formation rate, which is correlated with E(1/2), is discussed. Published by Elsevier Inc.
C1 [Samuni, Yuval; Ishii, Hisanari; Hyodo, Fuminori; Krishna, Murali C.; Mitchell, James B.] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA.
[Samuni, Uri] CUNY Queens Coll, Dept Chem & Biochem, Flushing, NY 11367 USA.
[Goldstein, Sara] Hebrew Univ Jerusalem, Accelerator Lab, Inst Chem, IL-91904 Jerusalem, Israel.
RP Krishna, MC (reprint author), NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA.
EM murali@helix.nih.gov
FU Intramural NIH HHS [Z01 BC010478-05]
NR 26
TC 30
Z9 30
U1 0
U2 14
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD JUN 1
PY 2010
VL 48
IS 11
BP 1559
EP 1563
DI 10.1016/j.freeradbiomed.2010.03.001
PG 5
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 598GG
UT WOS:000277822400012
PM 20211249
ER
PT J
AU Fontana, RJ
Sanyal, AJ
Ghany, MG
Lee, WM
Reid, AE
Naishadham, D
Everson, GT
Kahn, JA
Di Bisceglie, AM
Szabo, G
Morgan, TR
Everhart, JE
AF Fontana, Robert J.
Sanyal, Arun J.
Ghany, Marc G.
Lee, William M.
Reid, Andrea E.
Naishadham, Deepa
Everson, Gregory T.
Kahn, Jeffrey A.
Di Bisceglie, Adrian M.
Szabo, Gyongyi
Morgan, Timothy R.
Everhart, James E.
CA HALT-C Trial Grp
TI Factors That Determine the Development and Progression of
Gastroesophageal Varices in Patients With Chronic Hepatitis C
SO GASTROENTEROLOGY
LA English
DT Article
DE Cirrhosis; Portal Hypertension; Esophagogastroduodenoscopy; Hyaluronic
Acid
ID VENOUS-PRESSURE GRADIENT; ESOPHAGEAL-VARICES; ADVANCED FIBROSIS;
NATURAL-HISTORY; CIRRHOSIS; THERAPY; TRIAL; PEGINTERFERON; PREVALENCE;
VALIDATION
AB BACKGROUND & AIMS: We aimed to identify the incidence and predictors of de novo gastroesophageal variceal formation and progression in a large cohort of patients with chronic hepatitis C and advanced fibrosis. METHODS: All participants in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis Trial were offered an endoscopy before treatment and again after 4 years. Patients with varices at baseline also had an endoscopy at 2 years. Baseline laboratory and clinical parameters were analyzed as predictors of de novo variceal formation and variceal progression. RESULTS: De novo varices developed in 157 of the 598 (26.2%) patients. Most of the new varices were small (76.4%) and only 1% of patients developed variceal hemorrhage. The likelihood of developing varices was associated with subject race (Hispanic > Caucasian > African American; P = .0005), lower baseline levels of albumin (P = .051), and higher levels of hyaluronic acid (P < .001) with an area under the receiver operating characteristic curve = .70. Among 210 patients with existing gastroesophageal varices, 74 (35.2%) had variceal progression or bleeding during follow-up. Patients with higher baseline ratios of serum aspartate/alanine aminotransferase (P = .028) and lower platelet counts (P = .0002) were at greatest risk of variceal progression (area under the receiver operating characteristic = .72). Prolonged, low-dose peginterferon-alpha 2a therapy and beta-blockers did not influence the risk of developing new or enlarging varices. CONCLUSION: Development of varices in patients with chronic hepatitis C is associated with patient race/ethnicity and laboratory markers of disease severity. Prolonged low-dose peginterferon-alpha 2a therapy and beta-blockers do not reduce the risk of variceal development or progression.
C1 [Fontana, Robert J.] Univ Michigan, Dept Internal Med, Div Gastroenterol, Sch Med, Ann Arbor, MI 48109 USA.
[Sanyal, Arun J.] Virginia Commonwealth Univ, Dept Internal Med, Richmond, VA USA.
[Ghany, Marc G.] NIDDKD, Liver Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Everhart, James E.] NIDDKD, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA.
[Reid, Andrea E.] Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA.
[Naishadham, Deepa] New England Res Inst, Watertown, MA 02172 USA.
[Everson, Gregory T.] Univ Colorado Denver, Sect Hepatol, Div Gastroenterol & Hepatol, Sch Med, Aurora, CO USA.
[Kahn, Jeffrey A.] Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA 90033 USA.
[Di Bisceglie, Adrian M.] St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO USA.
[Szabo, Gyongyi] Univ Massachusetts, Sch Med, Dept Med, Hepatol & Liver Ctr,Div Gastroenterol, Worcester, MA USA.
[Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA.
[Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Irvine, CA USA.
RP Fontana, RJ (reprint author), Univ Michigan, Dept Internal Med, Div Gastroenterol, Sch Med, 3912 Taubman Ctr, Ann Arbor, MI 48109 USA.
EM rfontana@med.umich.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases;
National Institute of Allergy and Infectious Diseases (NIAID); National
Cancer Institute; National Center for Minority Health and Health
Disparities; National Center for Research Resources, National Institutes
of Health; Hoffmann-La Roche, Inc; University of Massachusetts Medical
Center, Worcester, MA [N01-DK-9-2326]; University of Connecticut Health
Center, Farmington, CT [M01RR-06192]; Saint Louis University School of
Medicine, St Louis, MO [N01-DK-9-2324]; Massachusetts General Hospital,
Boston, MA [N01-DK-9-2319, M01RR-01066, 1 UL1 RR025758-01]; University
of Colorado School of Medicine, Denver, CO [N01-DK-9-2327, M01RR-00051,
1 UL1 RR 025780-01]; Carol McKinley, RN University of California-Irvine,
Irvine, CA [N01-DK-9-2320, M01RR-00827]; University of Texas
Southwestern Medical Center, Dallas, TX [N01-DK-9-2321, M01RR-00633, 1
UL1 RR024982-01]; University of Southern California, Los Angeles, CA
[N01-DK-9-232, M01RR-00043]; University of Michigan Medical Center, Ann
Arbor, MI [N01-DK-9-2323, M01RR-00042, 1 UL1 RR024986]; Virginia
Commonwealth University Health System, Richmond, VA [N01-DK-9-2322,
M01RR-00065]; National Institute of Diabetes and Digestive and Kidney
Diseases, National Institutes of Health, Bethesda, MD; National
Institute of Diabetes and Digestive and Kidney Diseases, Division of
Digestive Diseases and Nutrition, Bethesda, MD; University of
Washington, Seattle, WA [N01-DK-9-2318]
FX In addition to the authors of this article, the following individuals
were instrumental in the planning, conduct and/or care of patients
enrolled in this study at each of the participating institutions as
follows: University of Massachusetts Medical Center, Worcester, MA:
(Contract N01-DK-9-2326) Gyongyi Szabo, MD, Barbara F. Banner, MD,
Maureen Cormier, RN, Donna Giansiracusa, RN; University of Connecticut
Health Center, Farmington, CT: (Grant M01RR-06192) Herbert L. Bonkovsky,
MD, Gloria Borders, RN, Michelle Kelley, RN, ANP; Saint Louis University
School of Medicine, St Louis, MO: (Contract N01-DK-9-2324) Adrian M. Di
Bisceglie, MD, Bruce Bacon, MD, Brent Neuschwander-Tetri, MD, Elizabeth
M. Brunt, MD, Debra King, RN; Massachusetts General Hospital, Boston,
MA: (Contract N01-DK-9-2319, Grant M01RR-01066; Grant 1 UL1 RR025758-01,
Harvard Clinical and Translational Science Center) Jules L. Dienstag,
MD, Raymond T. Chung, MD, Atul K. Bhan, MD, Wallis A. Molchen, Cara C.
Gooch; University of Colorado School of Medicine, Denver, CO: (Contract
N01-DK-9-2327, Grant M01RR-00051, Grant 1 UL1 RR 025780-01) Gregory T.
Everson, MD, S. Russell Nash, MD, Jennifer DeSanto, RN, Carol McKinley,
RN University of California-Irvine, Irvine, CA: (Contract N01-DK-9-2320,
Grant M01RR-00827) Timothy R. Morgan, MD, John C. Hoefs, MD, John R.
Craig, MD, M. Mazen Jamal, MD, MPH, Muhammad Sheikh, MD, Choon Park, RN;
University of Texas Southwestern Medical Center, Dallas, TX: (Contract
N01-DK-9-2321, Grant M01RR-00633, Grant 1 UL1 RR024982-01, North and
Central Texas Clinical and Translational Science Initiative) Thomas E.
Rogers, MD, Peter F. Malet, MD, Janel Shelton, Nicole Crowder, LVN,
Rivka Elbein, RN, BSN, Nancy Liston, MPH; University of Southern
California, Los Angeles, CA: (Contract N01-DK-9-2325, Grant M01RR-00043)
Karen L. Lindsay, MD, MMM, Sugantha Govindarajan, MD, Carol B. Jones,
RN, Susan L. Milstein, RN; University of Michigan Medical Center, Ann
Arbor, MI: (Contract N01-DK-9-2323, Grant M01RR-00042, Grant 1 UL1
RR024986, Michigan Center for Clinical and Health Research) Anna S. Lok,
MD, Joel K. Greenson, MD, Pamela A. Richtmyer, LPN, CCRC, R. Tess
Bonham, BS; Virginia Commonwealth University Health System, Richmond,
VA: (Contract N01-DK-9-2322, Grant M01RR-00065) Mitchell L. Shiffman,
MD, Richard K. Sterling, MD, Melissa J. Contos, MD, A. Scott Mills, MD,
Charlotte Hofmann, RN, Paula Smith, RN; Liver Diseases Branch, National
Institute of Diabetes and Digestive and Kidney Diseases, National
Institutes of Health, Bethesda, MD: T. Jake Liang, MD, David Kleiner,
MD, PhD, Yoon Park, RN, Elenita Rivera, RN, Vanessa Haynes-Williams, RN;
National Institute of Diabetes and Digestive and Kidney Diseases,
Division of Digestive Diseases and Nutrition, Bethesda, MD: James E.
Everhart, MD, Leonard B. Seeff, MD, Patricia R. Robuck, PhD, Jay H.
Hoofnagle, MD, Elizabeth C. Wright, PhD; University of Washington,
Seattle, WA: (Contract N01-DK-9-2318) Chihiro Morishima, MD, David R.
Gretch, MD, PhD, Minjun Chung Apodaca, BS, ASCP; New England Research
Institutes, Watertown, MA: (Contract N01-DK-9-2328) Kristin K. Snow,
MSc, ScD, Anne M. Stoddard, ScD, Teresa M. Curto, MSW, MPH; Armed Forces
Institute of Pathology, Washington, DC: Zachary D. Goodman, MD, PhD;
Data and Safety Monitoring Board Members: (Chair) Gary L. Davis, MD,
Guadalupe Garcia-Tsao, MD, Michael Kutner, PhD, Stanley M. Lemon, MD,
Robert P. Perrillo, MD. This is publication #48 from the HALT-C Trial
Group. The HALT-C Trial was registered with clinicaltrials.gov
(#NCT00006164).; This study was supported by the National Institute of
Diabetes and Digestive and Kidney Diseases (contract numbers are
listed). Additional support was provided by the National Institute of
Allergy and Infectious Diseases (NIAID), the National Cancer Institute,
the National Center for Minority Health and Health Disparities and by
General Clinical Research Center and Clinical and Translational Science
Center grants from the National Center for Research Resources, National
Institutes of Health (grant numbers are listed). The content is solely
the responsibility of the authors and does not necessarily represent the
official views of the National Center for Research Resources or the
National Institutes of Health. Additional funding to conduct this study
was supplied by Hoffmann-La Roche, Inc, through a Cooperative Research
and Development Agreement (CRADA) with the National Institutes of
Health.
NR 28
TC 21
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U1 1
U2 2
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD JUN
PY 2010
VL 138
IS 7
BP 2321
EP U176
DI 10.1053/j.gastro.2010.02.058
PG 13
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 602KB
UT WOS:000278136900024
PM 20211180
ER
PT J
AU Metais, JY
Topp, S
Doty, RT
Borate, B
Nguyen, AD
Wolfsberg, TG
Abkowitz, JL
Dunbar, CE
AF Metais, J-Y
Topp, S.
Doty, R. T.
Borate, B.
Nguyen, A-D
Wolfsberg, T. G.
Abkowitz, J. L.
Dunbar, C. E.
TI Feline leukemia virus integrase and capsid packaging functions do not
change the insertion profile of standard Moloney retroviral vectors
SO GENE THERAPY
LA English
DT Article
DE retroviral vector; insertion site analysis; viral packaging machinery;
feline leukemia virus
ID ACUTE MYELOID-LEUKEMIA; TARGET SITE SELECTION; GENE-THERAPY;
HEMATOPOIETIC-CELLS; CD34(+) CELLS; HUMAN GENOME; SCID-X1; DNA;
MUTAGENESIS; ACTIVATION
AB Adverse events linked to perturbations of cellular genes by vector insertion reported in gene therapy trials and animal models have prompted attempts to better understand the mechanisms directing viral vector integration. The integration profiles of vectors based on MLV, ASLV, SIV and HIV have all been shown to be non-random, and novel vectors with a safer integration pattern have been sought. Recently, we developed a producer cell line called CatPac that packages standard MoMLV vectors with feline leukemia virus (FeLV) gag, pol and env gene products. We now report the integration profile of this vector, asking if the FeLV integrase and capsid proteins could modify the MoMLV integration profile, potentially resulting in a less genotoxic pattern. We transduced rhesus macaque CD34+ hematopoietic progenitor cells with CatPac or standard MoMLV vectors, and determined their integration profile by LAM-PCR. We obtained 184 and 175 unique integration sites (ISs) respectively for CatPac and standard MoMLV vectors, and these were compared with 10 000 in silico-generated random IS. The integration profile for CatPac vector was similar to MoMLV and equally non-random, with a propensity for integration near transcription start sites and in highly dense gene regions. We found an IS for CatPac vector localized 715 nucleotides upstream of LMO-2, the gene involved in the acute lymphoblastic leukemia developed by X-SCID patients treated by gene therapy using MoMLV vectors. In conclusion, we found that replacement of MoMLV env, gag and pol gene products with FeLV did not alter the basic integration profile. Thus, there appears to be no safety advantage for this packaging system. However, considering the stability and efficacy of CatPac vectors, further development is warranted, using potentially safer vector backbones, for instance those with a SIN configuration. Gene Therapy (2010) 17, 799-804; doi: 10.1038/gt.2010.24; published online 18 March 2010
C1 [Metais, J-Y; Topp, S.; Dunbar, C. E.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Topp, S.] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
[Doty, R. T.; Abkowitz, J. L.] Univ Washington, Dept Med, Div Hematol, Seattle, WA 98195 USA.
[Borate, B.; Nguyen, A-D; Wolfsberg, T. G.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
RP Dunbar, CE (reprint author), NHLBI, Hematol Branch, NIH, CRC Bldg 10,Room 4E-5132,10 Ctr Dr, Bethesda, MD 20892 USA.
EM dunbarc@nhlbi.nih.gov
FU National Heart, Lung and Blood Institute; National Human Genome Research
Institute, National Institutes of Health
FX Jean-Yves Metais would like to dedicate this paper to his grandmother
Marie Pradier born Sautereau. This research was supported in part by the
Intramural Research Programs of the National Heart, Lung and Blood
Institute and the National Human Genome Research Institute, National
Institutes of Health. Raymond T Doty and Janis L Abkowitz are the
inventors on a patent filed for the CatPac producer cell line, which may
have potential for commercial use (patent application serial number
61/058,148). On request CatPac packaging cells will be supplied to
academic investigators.
NR 30
TC 4
Z9 4
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0969-7128
J9 GENE THER
JI Gene Ther.
PD JUN
PY 2010
VL 17
IS 6
BP 799
EP 804
DI 10.1038/gt.2010.24
PG 6
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity; Medicine, Research & Experimental
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity; Research & Experimental Medicine
GA 608GL
UT WOS:000278571400013
PM 20237508
ER
PT J
AU Tang, M
Zeng, Y
Poisson, A
Marti, D
Guan, L
Zheng, Y
Deng, H
Liao, J
Guo, X
Sun, S
Nelson, G
de The, G
Winkler, CA
O'Brien, SJ
Carrington, M
Gao, X
AF Tang, M.
Zeng, Y.
Poisson, A.
Marti, D.
Guan, L.
Zheng, Y.
Deng, H.
Liao, J.
Guo, X.
Sun, S.
Nelson, G.
de The, G.
Winkler, C. A.
O'Brien, S. J.
Carrington, M.
Gao, X.
TI Haplotype-dependent HLA susceptibility to nasopharyngeal carcinoma in a
Southern Chinese population
SO GENES AND IMMUNITY
LA English
DT Article
DE HLA; nasopharyngeal carcinoma; haplotype; stratified analysis
ID RISK-FACTORS; WUZHOU-CITY; CLASS-I; ASSOCIATION; MOLECULES; GUANGZHOU;
ANTIBODY; TAIWAN; LOCUS; DIET
AB We have conducted a comprehensive case-control study of a nasopharyngeal carcinoma (NPC) population cohort from Guangxi Province of Southern China, a region with one of the highest NPC incidences on record. A total of 1407 individuals including NPC patients, healthy controls, and their adult children were examined for the human leukocyte antigen (HLA) association, which is so far the largest NPC cohort reported for such studies. Stratified analysis performed in this study clearly demonstrated that while NPC protection is associated with independent HLA alleles, most NPC susceptibility is strictly associated with HLA haplotypes. Our study also detected for the first time that A*0206, a unique A2 subtype to South and Southeast Asia is also associated with a high risk for NPC. HLA-A*0206, HLA-B*3802 alleles plus the A*0207-B*4601 and A*3303-B*5801 haplotypes conferred high risk for NPC showing a combined odds ratio (OR) of 2.6 (P<0.0001). HLA alleles that associate with low risk for NPC include HLA-A*1101, B*27, and B*55 with a combined OR of 0.42 (P<0.0001). The overall high frequency of NPC-susceptible HLA factors in the Guangxi population is likely to have contributed to the high-NPC incidence in this region. Genes and Immunity (2010) 11, 334-342; doi:10.1038/gene.2009.109; published online 14 January 2010
C1 [Zeng, Y.; Guo, X.] Chinese Ctr Dis Control & Prevent, State Key Lab Infect Dis Prevent & Control, Inst Viral Dis Control & Prevent, Beijing 100052, Peoples R China.
[Tang, M.; O'Brien, S. J.] NCI, Lab Genom Divers, Frederick, MD 21702 USA.
[Tang, M.; Zheng, Y.; Deng, H.] Wuzhou Red Cross Hosp, Ctr Canc, Guangxi, Peoples R China.
[Poisson, A.; Marti, D.; Carrington, M.; Gao, X.] NCI, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21702 USA.
[Guan, L.; Guo, X.; Nelson, G.; Winkler, C. A.] NCI, Lab Genom Divers, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Liao, J.] Cangwu Inst Nasopharyngeal Carcinoma Control & Pr, Dept Epidemiol, Guangxi, Peoples R China.
[Sun, S.] Peking Univ, Coll Life Sci, Beijing 100871, Peoples R China.
[de The, G.] Inst Pasteur, Paris, France.
RP Zeng, Y (reprint author), Chinese Ctr Dis Control & Prevent, State Key Lab Infect Dis Prevent & Control, Inst Viral Dis Control & Prevent, Beijing 100052, Peoples R China.
EM zengy@public.bta.net.cn; carringt@ncifcrf.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 No. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the US Government. This
Research was supported in part by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research.
NR 29
TC 22
Z9 32
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1466-4879
J9 GENES IMMUN
JI Genes Immun.
PD JUN
PY 2010
VL 11
IS 4
BP 334
EP 342
DI 10.1038/gene.2009.109
PG 9
WC Genetics & Heredity; Immunology
SC Genetics & Heredity; Immunology
GA 604PM
UT WOS:000278291000006
PM 20072141
ER
PT J
AU Lakshman, R
Garige, M
Gong, M
Leckey, L
Varatharajalu, R
Zakhari, S
AF Lakshman, Raj
Garige, Mamatha
Gong, Maokai
Leckey, Leslie
Varatharajalu, Ravi
Zakhari, Samir
TI Is alcohol beneficial or harmful for cardioprotection?
SO GENES AND NUTRITION
LA English
DT Review
DE Coronary artery disease; Paraoxonase; Homocysteine thiolactonase;
Sterol-regulatory element-binding protein; Ethanol; Quercetin
ID LOW-DENSITY-LIPOPROTEIN; CORONARY-HEART-DISEASE; REVERSE CHOLESTEROL
TRANSPORT; INCREASES SERUM PARAOXONASE; ACUTE MYOCARDIAL-INFARCTION;
CHRONIC ETHANOL-CONSUMPTION; INDUCED FATTY LIVER; APOLIPOPROTEIN-A-I;
CARDIOVASCULAR-DISEASE; BINGE DRINKING
AB While the effects of chronic ethanol consumption on liver have been well studied and documented, its effect on the cardiovascular system is bimodal. Thus, moderate drinking in many population studies is related to lower prevalence of coronary artery disease (CAD). In contrast, heavy drinking correlates with higher prevalence of CAD. In several other studies of cardiovascular mortalities, abstainers and heavy drinkers are at higher risk than light or moderate drinkers. The composite of this disparate relation in several population studies of cardiovascular mortality has been a "U-" or "J-" shaped curve. Apart from its ability to eliminate cholesterol from the intima of the arteries by reverse cholesterol transport, another major mechanism by which HDL may have this cardioprotective property is by virtue of the ability of its component enzyme paraoxonase1 (PON1) to inhibit LDL oxidation and/or inactivate OxLDL. Therefore, PON1 plays a central role in the disposal of OxLDL and thus is antiatherogenic. Furthermore, PON1 is a multifunctional antioxidant enzyme that can also detoxify the homocysteine metabolite, homocysteine thiolactone (HTL), which can pathologically cause protein damage by homocysteinylation of the lysine residues, thereby leading to atherosclerosis. We demonstrated that moderate alcohol up regulates liver PON1 gene expression and serum activity, whereas heavy alcohol consumption had the opposite effects in both animal models and in humans. The increase in PON1 activity in light drinkers was not due to preferential distribution of high PON1 genotype in this group. It is well known that wine consumption in several countries shows a remarkable inverse correlation to local rates of CAD mortality. Significantly, apart from its alcohol content, red wine also has polyphenols such as quercetin and resveratrol that are also known to have cardioprotective effects. We have shown that quercetin also up regulates PON1 gene in rats and in human liver cells. The action of quercetin seems to be mediated via the active form of the nuclear lipogenic transcription factor, sterol-regulatory element-binding protein 2 (SREBP2) that is translocated from endoplasmic reticulum to the nucleus. However, the mechanism of action of ethanol-mediated up-regulation of PON1 gene remains to be elucidated. We conclude that both moderate ethanol and quercetin, the two major components of red wine, exhibit cardioprotective properties via the up-regulation of the antiatherogenic gene PON1.
C1 [Lakshman, Raj; Leckey, Leslie] VA Med Ctr, Lipid Res Lab, Washington, DC 20422 USA.
[Lakshman, Raj; Garige, Mamatha; Gong, Maokai; Varatharajalu, Ravi] George Washington Univ, Dept Biochem & Mol Biol, Washington, DC 20037 USA.
[Zakhari, Samir] NIAAA, Div Metab & Hlth Effects, NIH, Bethesda, MD 20892 USA.
RP Lakshman, R (reprint author), VA Med Ctr, Lipid Res Lab, Washington, DC 20422 USA.
EM raj.lakshman@va.gov
OI LAKSHMAN, RAJ/0000-0003-2415-4509
FU VA; NIH
FX This work was supported by grants from VA Merit Review as well as from
NIH (M.R. Lakshman). Authors gratefully acknowledge the Editors of the
journal "Biochemical Biophysical Research Communications" for giving
permission to reproduce some of the tables and figures reproduced in
this review article.
NR 118
TC 12
Z9 12
U1 1
U2 13
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1555-8932
J9 GENES NUTR
JI Genes Nutr.
PD JUN
PY 2010
VL 5
IS 2
SI SI
BP 111
EP 120
DI 10.1007/s12263-009-0161-2
PG 10
WC Genetics & Heredity; Nutrition & Dietetics
SC Genetics & Heredity; Nutrition & Dietetics
GA 623RU
UT WOS:000279761100003
PM 20012900
ER
PT J
AU Tremblay, M
Tremblay, CS
Herblot, S
Aplan, PD
Hebert, J
Perreault, C
Hoang, T
AF Tremblay, Mathieu
Tremblay, Cedric S.
Herblot, Sabine
Aplan, Peter D.
Hebert, Josee
Perreault, Claude
Hoang, Trang
TI Modeling T-cell acute lymphoblastic leukemia induced by the SCL and LMO1
oncogenes
SO GENES & DEVELOPMENT
LA English
DT Review
DE T-ALL; Notch1; SCL/TAL1; LMO1; leukemia-initiating cell; pre-TCR
ID ACUTE MYELOID-LEUKEMIA; PRE-TCR; TRANSGENIC MICE; THYMOCYTE
DIFFERENTIATION; GENE-EXPRESSION; INSERTIONAL MUTAGENESIS; MOLECULAR
PATHOGENESIS; E2A-DEFICIENT MICE; SIGNALING PROMOTES; NOTCH1 MUTATIONS
AB Deciphering molecular events required for full transformation of normal cells into cancer cells remains a challenge. In T-cell acute lymphoblastic leukemia (T-ALL), the genes encoding the TAL1/SCL and LMO1/2 transcription factors are recurring targets of chromosomal translocations, whereas NOTCH1 is activated in >50% of samples. Here we show that the SCL and LMO1 oncogenes collaborate to expand primitive thymocyte progenitors and inhibit later stages of differentiation. Together with pre-T-cell antigen receptor (pre-TCR) signaling, these oncogenes provide a favorable context for the acquisition of activating Notch1 mutations and the emergence of self-renewing leukemia-initiating cells in T-ALL. All tumor cells harness identical and specific Notch1 mutations and Tcr beta clonal signature, indicative of clonal dominance and concurring with the observation that Notch1 gain of function confers a selective advantage to SCL-LMO1 transgenic thymocytes. Accordingly, a hyperactive Notch1 allele accelerates leukemia onset induced by SCL-LMO1 and bypasses the requirement for pre-TCR signaling. Finally, the time to leukemia induced by the three transgenes corresponds to the time required for clonal expansion from a single leukemic stem cell, suggesting that SCL, LMO1, and Notch1 gain of function, together with an active pre-TCR, might represent the minimum set of complementing events for the transformation of susceptible thymocytes.
C1 [Tremblay, Mathieu; Tremblay, Cedric S.; Herblot, Sabine; Perreault, Claude; Hoang, Trang] Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada.
[Aplan, Peter D.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Hebert, Josee] Maisonneuve Rosemont Hosp, Montreal, PQ H1T 2M4, Canada.
[Hoang, Trang] Univ Montreal, Fac Med, Dept Pharmacol, Montreal, PQ H3C 3J7, Canada.
[Hoang, Trang] Univ Montreal, Fac Med, Dept Biochem, Montreal, PQ H3C 3J7, Canada.
[Hoang, Trang] Univ Montreal, Fac Med, Dept Mol Biol, Montreal, PQ H3C 3J7, Canada.
RP Hoang, T (reprint author), Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada.
EM trang.hoang@umontreal.ca
RI Perreault, Claude/A-7220-2008; Aplan, Peter/K-9064-2016
OI Perreault, Claude/0000-0001-9453-7383;
FU Canadian Cancer Society Research Institute; Canada Research Chair
program; Fonds de Recherche en Sante du Quebec (FRSQ); Cole Foundation;
Canadian Institute for Health Research (CIHR); Leukemia Research Fund of
Canada; Terry Fox Foundation [700153]
FX We thank Daniele Gagne (IRIC) for her assistance with cell sorting, and
Veronique Litalien for mice handling. This work was funded by grants
from the Canadian Cancer Society Research Institute (T. H.) and the
Canada Research Chair program (T. H.). The Quebec Leukemia Cell Bank is
supported in part by funds from the Fonds de Recherche en Sante du
Quebec (FRSQ) and by the Cole Foundation (J.H.). The flow cytometry
service was supported by a Multiuser grant from the Canadian Institute
for Health Research (CIHR), and the infrastructure was supported in part
by an FRSQ group grant (IRIC). M. T. received doctoral awards from CIHR
and the Cole Foundation, S. H. received a post-doctoral fellowship from
the Leukemia Research Fund of Canada, and C. S. T. received a
post-doctoral Research Fellowship of the Terry Fox Foundation Award
(#700153).
NR 76
TC 47
Z9 47
U1 0
U2 9
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI WOODBURY
PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA
SN 0890-9369
J9 GENE DEV
JI Genes Dev.
PD JUN 1
PY 2010
VL 24
IS 11
BP 1093
EP 1105
DI 10.1101/gad.1897910
PG 13
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA 604GJ
UT WOS:000278267200005
PM 20516195
ER
PT J
AU Wade, CH
Wilfond, BS
McBride, CM
AF Wade, Christopher H.
Wilfond, Benjamin S.
McBride, Colleen M.
TI Effects of genetic risk information on children's psychosocial
wellbeing: A systematic review of the literature
SO GENETICS IN MEDICINE
LA English
DT Review
DE genetic testing; children; self-identity; psychosocial wellbeing;
relationships; emotions; systematic review
ID X-LINKED DISEASES; AFRICAN-AMERICAN ADULTS; HIGH-SCHOOL-STUDENTS;
YOUNG-PEOPLE; PSYCHOLOGICAL IMPACT; BREAST-CANCER;
CARDIOVASCULAR-DISEASES; HUNTINGTONS-DISEASE; EMPIRICAL-RESEARCH;
COLORECTAL-CANCER
AB Purpose: As advances in research have made a growing number of genetic tests available, clinicians will increasingly be faced with making decisions about when offering genetic testing services to children is appropriate. A key factor in such decisions involves determining whether knowledge of genetic health risks might have an impact on children's psychosocial wellbeing. Methods: We conducted a systematic review of the literature using five online databases to identify studies that assessed the impact of communicating nondiagnostic carrier or presymptomatic genetic test results to children. Results: A total of 17 articles met the inclusion criteria for this review. These studies used a wide range of methodologies to explore carrier and predictive testing. Although there was little quantitative evidence that receiving genetic test results led to a significant impact on children's psychosocial wellbeing, it was found that methodological inconsistencies, small samples, and reliance on assessments most appropriate for psychopathology make any firm conclusions about the impact of genetic testing on children premature. Conclusion: Currently, there is insufficient evidence to inform a nuanced understanding of how children respond to genetic testing. This suggests a strong need for further research that uses rigorous approaches to address children's emotional states, self-perception, and social wellbeing. Genet Med 2010: 12(6): 317-326.
C1 [Wade, Christopher H.; McBride, Colleen M.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
[Wade, Christopher H.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Wilfond, Benjamin S.] Seattle Childrens Hosp, Treuman Katz Ctr Pediat Bioeth, Seattle, WA USA.
[Wilfond, Benjamin S.] Univ Washington, Sch Med, Dept Pediat, Div Bioeth, Seattle, WA 98195 USA.
RP Wade, CH (reprint author), 31 Ctr Dr,Bldg 31,Room B1B45F, Bethesda, MD 20892 USA.
EM wadec@mail.nih.gov
FU National Human Genome Research Institute, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Human Genome Research Institute, National Institutes of Health.
The authors thank Dr. Kenneth Tercyak for his helpful suggestions.
NR 75
TC 38
Z9 38
U1 4
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1098-3600
J9 GENET MED
JI Genet. Med.
PD JUN
PY 2010
VL 12
IS 6
BP 317
EP 326
DI 10.1097/GIM.0b013e3181de695c
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 609EO
UT WOS:000278638400001
PM 20445458
ER
PT J
AU Johnson, AD
Bhimavarapu, A
Benjamin, EJ
Fox, C
Levy, D
Jarvik, GP
O'Donnell, CJ
AF Johnson, Andrew D.
Bhimavarapu, Anupama
Benjamin, Emelia J.
Fox, Caroline
Levy, Daniel
Jarvik, Gail P.
O'Donnell, Christopher J.
TI CLIA-tested genetic variants on commercial SNP arrays: Potential for
incidental findings in genome-wide association studies
SO GENETICS IN MEDICINE
LA English
DT Article
DE SNP; GWAS; incidental finding; return of results; genetic
ID RECURRENT VENOUS THROMBOEMBOLISM; FAMILIAL MEDITERRANEAN FEVER;
HEREDITARY HEMOCHROMATOSIS; LONG-TERM; FRAMINGHAM; RECOMMENDATIONS;
PANCREATITIS; POPULATION; MUTATIONS; DIAGNOSIS
AB Purpose: Increases in throughput and affordability of genotyping products have led to large sample sizes in genetic studies, increasing the likelihood that incidental genetic findings may occur. We set out to survey potential notifiable variants on arrays used in genome-wide association studies and in direct-to-consumer genetic services. Methods: We used multiple bioinformatics strategies to identify, and map variants tested for genetic disorders in >= 2 CLIA-approved laboratories (based on the GeneTests database). We subsequently surveyed 18 commercial single nucleotide polymorphism arrays and HapMap for these variants. Results: Of 1,362 genes tested according to GeneTests, we identified 298 specific targeted mutations measured in more than or equal to two laboratories, encompassing 56 disorders. Only 88 of 298 mutations could be identified as known single nucleotide polymorphisms in genomic databases. We found 18 of 88 single nucleotide polymorphisms present in HapMap or on commercial single nucleotide polymorphism arrays. Homozygotes for rare alleles of some variants were identified in the Framingham Heart Study, an active genome-wide association studies cohort (n = 8,410). Conclusions: Variants in genes including APOE, F5, HFE, CYP21A2, MEFV, SPINK1, BTD, GALT, and G6PD were found on single nucleotide polymorphism arrays or in the HapMap. Some of these variants may warrant further review to determine their likelihood to trigger incidental findings in the course of genome-wide association studies or direct-to- consumer testing. Genet Med 2010:12(6):355-363.
C1 [Johnson, Andrew D.; Bhimavarapu, Anupama; Benjamin, Emelia J.; Fox, Caroline; Levy, Daniel; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[Johnson, Andrew D.; Bhimavarapu, Anupama; Fox, Caroline; Levy, Daniel; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA.
[Johnson, Andrew D.; Bhimavarapu, Anupama; Fox, Caroline; Levy, Daniel; O'Donnell, Christopher J.] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
[Benjamin, Emelia J.; Levy, Daniel] Boston Univ, Div Cardiol, Sch Med & Publ Hlth, Boston, MA 02215 USA.
[Jarvik, Gail P.] Univ Washington, Med Ctr, Div Med Genet, Seattle, WA 98195 USA.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
RP O'Donnell, CJ (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM odonnellc@nhlbi.nih.gov
RI Johnson, Andrew/G-6520-2013; Jarvik, Gail/N-6476-2014;
OI Jarvik, Gail/0000-0002-6710-8708; Benjamin, Emelia/0000-0003-4076-2336
FU National Heart, Lung and Blood Institute's Framingham Heart Study
[N01-HC-25195]; NHLBI; NIH; State of Washington Life Sciences Discovery
Fund
FX Supported by the National Heart, Lung and Blood Institute's Framingham
Heart Study (Contract No. N01-HC-25195). ADJ was supported by an NHLBI
IRTA fellowship award. AB was supported by the NIH Summer Internship
Program in Biomedical Research. GPJ was supported by a State of
Washington Life Sciences Discovery Fund.
NR 37
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U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1098-3600
J9 GENET MED
JI Genet. Med.
PD JUN
PY 2010
VL 12
IS 6
BP 355
EP 363
DI 10.1097/GIM.0b013e3181e1e2a9
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 609EO
UT WOS:000278638400005
PM 20556870
ER
PT J
AU Facio, FM
Feero, WG
Linn, A
Oden, N
Manickam, K
Biesecker, LG
AF Facio, Flavia M.
Feero, W. Gregory
Linn, Amy
Oden, Neal
Manickam, Kandamurugu
Biesecker, Leslie G.
TI Validation of My Family Health Portrait for six common heritable
conditions
SO GENETICS IN MEDICINE
LA English
DT Article
DE My Family Health Portrait; common disease; family history; risk
assessment; pedigree
ID CORONARY-HEART-DISEASE; RISK-ASSESSMENT; GENETIC RISK; PRIMARY-CARE;
BREAST-CANCER; HISTORY DATA; TOOL; PREVENTION; MEDICINE; WOMEN
AB Purpose: To assess the ability of My Family Health Portrait to accurately collect family history for six common heritable disorders. Background: Family history is useful to assess disease risk but is not widely used. We compared the pedigree from My Family Health Portrait, an online tool for collection of family history, to a pedigree supplemented by a genetics professional. Methods: One hundred fifty volunteers collected their family histories using My Family Health Portrait. A genetic counselor interviewed the volunteers to validate the entries and add diagnoses, as needed. The content and the affection assignments of the pedigrees were compared. The pedigrees were entered into Family Healthware (TM) to assess risks for the diseases. Results: The sensitivity of My Family Health Portrait varied among the six diseases (67-100%) compared to the supplemented pedigree. The specificities ranged from 92 to 100%. When the pedigrees were used to generate risk scores, My Family Health Portrait yielded identical risks to the supplemented pedigree for 94-99% of the volunteers for diabetes and colon, breast, and ovarian cancer. The agreement was lower for coronary artery disease (68%) and stroke (83%). Conclusions: These data support the validity of My Family Health Portrait pedigrees for four common conditions-diabetes and colon, breast, and ovarian cancer. The tool performed less well for coronary artery disease and stroke. We recommend that the tool be improved to better capture information for these two common conditions. Genet Med 2010: 12(6):370-375.
C1 [Facio, Flavia M.; Feero, W. Gregory; Linn, Amy; Manickam, Kandamurugu; Biesecker, Leslie G.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Feero, W. Gregory] Maine Dartmouth Family Med Residency Program, Augusta, ME USA.
[Oden, Neal] EMMES Corp, Rockville, MD USA.
RP Facio, FM (reprint author), NHGRI, NIH, 10 Ctr Dr,Room 3C710, Bethesda, MD 20892 USA.
EM ffacio@mail.nih.gov
RI Manickam, Kandamurugu/E-3585-2011
FU National Human Genome Research Institute
FX This study was supported by funding from the Intramural Research Program
of the National Human Genome Research Institute.
NR 36
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Z9 34
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1098-3600
J9 GENET MED
JI Genet. Med.
PD JUN
PY 2010
VL 12
IS 6
BP 370
EP 375
DI 10.1097/GIM.0b013e3181e15bd5
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA 609EO
UT WOS:000278638400007
PM 20479646
ER
PT J
AU Ertem, G
Schuhmann, R
Steudel, A
Emmerich, K
Hazen, RM
AF Ertem, G.
Schuhmann, R.
Steudel, A.
Emmerich, K.
Hazen, R. M.
TI Montmorillonite catalysis and potential of charge density in proposing
the target sites on Mars for search of organics
SO GEOCHIMICA ET COSMOCHIMICA ACTA
LA English
DT Meeting Abstract
CT Conference on Goldschmidt 2010 - Earth, Energy, and the Environment
CY JUN 13-18, 2010
CL Knoxville, TN
C1 [Ertem, G.] SETI Inst, Carl Sagan Ctr, Mountain View, CA 94043 USA.
[Ertem, G.] NIH, Bethesda, MD 20892 USA.
[Schuhmann, R.; Steudel, A.; Emmerich, K.] Karlsruhe Inst Technol, Karlsruhe, Germany.
[Hazen, R. M.] Carnegie Inst Sci, Geophys Lab, Washington, DC 20015 USA.
EM gertem@carlsagancenter.org
NR 6
TC 0
Z9 0
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0016-7037
J9 GEOCHIM COSMOCHIM AC
JI Geochim. Cosmochim. Acta
PD JUN
PY 2010
VL 74
IS 12
SU 1
BP A271
EP A271
PG 1
WC Geochemistry & Geophysics
SC Geochemistry & Geophysics
GA 676TL
UT WOS:000283941400791
ER
PT J
AU Colsch, B
Woods, AS
AF Colsch, Benoit
Woods, Amina S.
TI Localization and imaging of sialylated glycosphingolipids in brain
tissue sections by MALDI mass spectrometry
SO GLYCOBIOLOGY
LA English
DT Article
DE brain; gangliosides; imaging; MALDI; mass spectrometry
ID THIN-LAYER-CHROMATOGRAPHY; ION MOBILITY-TOFMS; GANGLIOSIDE; MATRIX;
TECHNOLOGY; METABOLISM; EXPRESSION; PROTEINS; DISEASES; LIPIDS
AB In this study, we describe a simple and efficient method for mapping the distribution and localization of all sialylated sphingoglycolipids present in coronal mouse brain sections using a conventional axial matrix-assisted laser desorption/ionization time of flight. A single scan of a histological tissue section gives a complete profile of ganglioside species without derivatization or labeling. We have developed and tested a new matrix preparation (2,6-dihydroxyacetophenone [DHA]/ammonium sulfate/heptafluorobutyric acid [HFBA]) to maximize the detection of all ganglioside species; the ammonium sulfate limits the formation of salt adducts, while the addition of HFBA increases the stability of DHA in a vacuum, thus facilitating imaging applications. Our results, in both extracted samples and whole tissue sections using negative ion reflectron and linear modes, show differences in localization in several brain regions depending on the sialic acids and the ceramide-associated core gangliosides.
C1 [Colsch, Benoit; Woods, Amina S.] NIDA IRP, NIH, Baltimore, MD 21224 USA.
RP Woods, AS (reprint author), NIDA IRP, NIH, Baltimore, MD 21224 USA.
EM awoods@mail.nih.gov
FU National Institute on Drug Abuse, NIH; Office of National Drug Control
Policy (ONDCP); Shimadzu Scientific Instruments
FX This research was supported by the Intramural Research Program of the
National Institute on Drug Abuse, NIH. We thank the Office of National
Drug Control Policy (ONDCP) for instrumentation funding, without which
this and other projects could not have been accomplished. We also would
like to thank Steve Wishnies (Shimadzu Scientific Instruments) for
technical support.
NR 29
TC 50
Z9 51
U1 3
U2 25
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD JUN
PY 2010
VL 20
IS 6
BP 661
EP 667
DI 10.1093/glycob/cwq031
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 593IW
UT WOS:000277448400002
PM 20190299
ER
PT J
AU Wilson, H
O'Connor, A
Czuczman, S
LaCasce, S
Gerecitano, F
Leonard, P
Tulpule, A
Xiong, H
Chiu, YL
Busman, T
Enschede, H
Krivoshik, P
Humerickhouse, H
AF Wilson, H.
O'Connor, A.
Czuczman, S.
LaCasce, S.
Gerecitano, F.
Leonard, P.
Tulpule, A.
Xiong, H.
Chiu, Y. L.
Busman, T.
Enschede, H.
Krivoshik, P.
Humerickhouse, H.
TI PHASE 1/2A STUDY OF NAVITOCLAX (ABT-263) IN RELAPSED OR REFRACTORY
LYMPHOID MALIGNANCIES
SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the European-Hematology-Association
CY JUN 10-13, 2010
CL Barcelona, SPAIN
SP European Hematol Assoc
C1 [Wilson, H.] NCI, Bethesda, MD 20892 USA.
[O'Connor, A.] NYU, Inst Canc, New York, NY USA.
[Czuczman, S.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[LaCasce, S.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Gerecitano, F.] Mem Sloan Kettering Canc Ctr, New York, NY USA.
[Leonard, P.] Weill Cornell Med Coll, New York, NY USA.
[Tulpule, A.] USC Kenneth Norris Canc Hosp, Canc Hosp & Res Inst, Los Angeles, CA USA.
[Xiong, H.; Chiu, Y. L.; Busman, T.; Enschede, H.; Krivoshik, P.; Humerickhouse, H.] Abbott Labs, Abbott Pk, IL 60064 USA.
RI Jones, Jeffrey/E-9827-2013
NR 0
TC 1
Z9 1
U1 1
U2 1
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOL-HEMATOL J
JI Haematol-Hematol. J.
PD JUN
PY 2010
VL 95
SU 2
MA 0292
BP 116
EP 117
PG 2
WC Hematology
SC Hematology
GA 614IY
UT WOS:000279051300292
ER
PT J
AU Cea, M
Cagnetta, A
Garuti, A
Cirmena, G
Rocco, I
Palermo, C
Soncini, D
Caffa, I
Zoppoli, G
Pierri, I
Gobbi, M
Ballestrero, A
Nencioni, A
Patrone, F
AF Cea, M.
Cagnetta, A.
Garuti, A.
Cirmena, G.
Rocco, I.
Palermo, C.
Soncini, D.
Caffa, I.
Zoppoli, G.
Pierri, I.
Gobbi, M.
Ballestrero, A.
Nencioni, A.
Patrone, F.
TI HDAC INHIBITORS SYNERGISTICALLY ENHANCE AP0866 ACTIVITY IN HUMAN
LEUKEMIA CELLS: EVIDENCE FOR CONVERGING MECHANISMS OF SIRT1 INHIBITION
SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the European-Hematology-Association
CY JUN 10-13, 2010
CL Barcelona, SPAIN
SP European Hematol Assoc
C1 [Cea, M.; Cagnetta, A.; Garuti, A.; Cirmena, G.; Rocco, I.; Palermo, C.; Soncini, D.; Caffa, I.; Pierri, I.; Gobbi, M.; Ballestrero, A.; Nencioni, A.; Patrone, F.] Univ Genoa, Genoa, Italy.
[Zoppoli, G.] NIH, Bethesda, MD 20892 USA.
RI Caffa, Irene/J-9835-2016
OI Caffa, Irene/0000-0003-1111-9915
NR 0
TC 0
Z9 0
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 JUN
PY 2010
VL 95
SU 2
MA 0440
BP 179
EP 180
PG 2
WC Hematology
SC Hematology
GA 614IY
UT WOS:000279051300439
ER
PT J
AU Coiffier, B
Horwitz, S
Whittaker, S
Pro, B
Robak, T
Samtsov, A
Kim, Y
Prince, M
Foss, F
Piekarz, R
Nichols, J
Bates, S
AF Coiffier, B.
Horwitz, S.
Whittaker, S.
Pro, B.
Robak, T.
Samtsov, A.
Kim, Y.
Prince, M.
Foss, F.
Piekarz, R.
Nichols, J.
Bates, S.
TI ROMIDEPSIN EXPERIENCE IN 317 PATIENTS WITH T-CELL LYMPHOMAS
SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the European-Hematology-Association
CY JUN 10-13, 2010
CL Barcelona, SPAIN
SP European Hematol Assoc
C1 [Coiffier, B.] Hospices Civils Lyon, Pierre Benite, France.
[Horwitz, S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Whittaker, S.] Guys & St Thomas NHS Fdn Trust, London, England.
[Pro, B.] MD Anderson Canc Ctr, Houston, TX USA.
[Robak, T.] Med Univ Lodz, Lodz, Poland.
[Robak, T.] Copernicus Mem Hosp, Lodz, Poland.
[Samtsov, A.] Russian Federat Med Mil Acad, St Petersburg, Russia.
[Kim, Y.] Stanford Canc Ctr, Stanford, CA USA.
[Prince, M.] Peter MacCallum Canc Ctr, Melbourne, Australia.
[Foss, F.] Yale Canc Ctr, New Haven, CT USA.
[Piekarz, R.] Natl Canc Inst, Rockville, MD USA.
[Nichols, J.] Celgene Oncol, Cambridge, MA USA.
[Bates, S.] Natl Canc Inst, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
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 JUN
PY 2010
VL 95
SU 2
MA 0572
BP 238
EP 238
PG 1
WC Hematology
SC Hematology
GA 614IY
UT WOS:000279051300573
ER
PT J
AU Cokic, V
Mojsilovic, S
Miloksevic, V
Kraguljac-Kurtovic, N
Bogdanovic, A
Jovcic, G
Milenkovic, P
Gotic, M
Noguchi, C
Schechter, A
AF Cokic, V.
Mojsilovic, S.
Miloksevic, V.
Kraguljac-Kurtovic, N.
Bogdanovic, A.
Jovcic, G.
Milenkovic, P.
Gotic, M.
Noguchi, C.
Schechter, A.
TI GENE EXPRESSION PROFILE OF HEMATOPOIETIC PROGENITOR CELLS VS.
GRANULOCYTES IN CHRONIC MYELOID LEUKEMIA
SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the European-Hematology-Association
CY JUN 10-13, 2010
CL Barcelona, SPAIN
SP European Hematol Assoc
C1 [Cokic, V.; Mojsilovic, S.; Jovcic, G.; Milenkovic, P.] Med Res Inst, Belgrade, Serbia.
[Miloksevic, V.; Kraguljac-Kurtovic, N.; Bogdanovic, A.] Univ Clin Ctr, Inst Hematol, Belgrade, Serbia.
[Noguchi, C.; Schechter, A.] NIDDK, Mol Med Branch, Natl Inst Hlth, Bethesda, MD USA.
NR 0
TC 0
Z9 0
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 JUN
PY 2010
VL 95
SU 2
MA 0799
BP 334
EP 335
PG 2
WC Hematology
SC Hematology
GA 614IY
UT WOS:000279051301119
ER
PT J
AU Cokic, V
Han, J
Beleslin-Cokic, B
Mirkovic, K
Damjanovic, S
Gotic, M
Raj, P
Noguchi, C
Schechter, A
AF Cokic, V.
Han, J.
Beleslin-Cokic, B.
Mirkovic, K.
Damjanovic, S.
Gotic, M.
Raj, P.
Noguchi, C.
Schechter, A.
TI THERAPY RELATED GENE EXPRESSION OF HEMATOPOIETIC PROGENITOR CELLS IN
CHRONIC MYELOPROLIFERATIVE NEOPLASMS
SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the European-Hematology-Association
CY JUN 10-13, 2010
CL Barcelona, SPAIN
SP European Hematol Assoc
C1 [Cokic, V.] Inst Med Res, Belgrade, Serbia.
[Han, J.; Raj, P.] FDA, Ctr Biol Evaluation & Res, Bethesda, MD USA.
[Beleslin-Cokic, B.; Mirkovic, K.; Damjanovic, S.] Inst Endocrinol, Belgrade, Serbia.
[Gotic, M.] Univ Clin Ctr, Inst Hematol, Belgrade, Serbia.
[Noguchi, C.; Schechter, A.] NID DK, Natl Inst Hlth, Mol Med Branch, Bethesda, MD USA.
NR 0
TC 0
Z9 0
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 JUN
PY 2010
VL 95
SU 2
MA 0973
BP 403
EP 403
PG 1
WC Hematology
SC Hematology
GA 614IY
UT WOS:000279051301294
ER
PT J
AU Hultcrantz, L
Kristinsson, S
Andersson, T
Eloranta, S
Derolf, A
Landgren, O
Dickman, P
Bjorkholm, M
AF Hultcrantz, L.
Kristinsson, S.
Andersson, T.
Eloranta, S.
Derolf, A.
Landgren, O.
Dickman, P.
Bjorkholm, M.
TI PATTERNS OF SURVIVAL AMONG 7,249 PATIENTS WITH MYELOPROLIFERATIVE
NEOPLASMS DIAGNOSED IN SWEDEN 1973-2003
SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the European-Hematology-Association
CY JUN 10-13, 2010
CL Barcelona, SPAIN
SP European Hematol Assoc
C1 [Hultcrantz, L.; Kristinsson, S.; Andersson, T.; Eloranta, S.; Derolf, A.; Dickman, P.; Bjorkholm, M.] Karolinska Inst, Stockholm, Sweden.
[Landgren, O.] Natl Inst Hlth, Bethesda, MD USA.
RI Kristinsson, Sigurdur /M-2910-2015; Andersson, Therese/E-7107-2016
OI Kristinsson, Sigurdur /0000-0002-4964-7476; Andersson,
Therese/0000-0001-8644-9041
NR 0
TC 0
Z9 0
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 JUN
PY 2010
VL 95
SU 2
MA 1140
BP 470
EP 470
PG 1
WC Hematology
SC Hematology
GA 614IY
UT WOS:000279051301461
ER
PT J
AU Clark, WB
Strickland, SA
Barrett, AJ
Savani, BN
AF Clark, William B.
Strickland, Stephen A.
Barrett, A. John
Savani, Bipin N.
TI Extramedullary relapses after allogeneic stem cell transplantation for
acute myeloid leukemia and myelodysplastic syndrome
SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
LA English
DT Editorial Material
ID BONE-MARROW-TRANSPLANTATION; GRANULOCYTIC SARCOMA; AML RELAPSE; THERAPY;
SITES; SCT
C1 [Clark, William B.; Strickland, Stephen A.] Vanderbilt Univ, Hematol & Stem Cell Transplantat Sect, Hematol & Stem Cell Transplant Program, Dept Med,Div Hematol Oncol,Med Ctr, Nashville, TN 37235 USA.
[Barrett, A. John] NHLBI, Stem Cell Transplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Stem Cell Transplant Program, Nashville, TN USA.
[Savani, Bipin N.] Natl VA Transplant Program, Nashville, TN USA.
RP Clark, WB (reprint author), Vanderbilt Univ, Hematol & Stem Cell Transplantat Sect, Hematol & Stem Cell Transplant Program, Dept Med,Div Hematol Oncol,Med Ctr, Nashville, TN 37235 USA.
EM bipin.savani@vanderbilt.edu
OI Strickland, Stephen/0000-0002-6861-2041
NR 22
TC 24
Z9 26
U1 0
U2 1
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOL-HEMATOL J
JI Haematol-Hematol. J.
PD JUN
PY 2010
VL 95
IS 6
BP 860
EP 863
DI 10.3324/haematol.2010.025890
PG 4
WC Hematology
SC Hematology
GA 614IW
UT WOS:000279051100003
PM 20513805
ER
PT J
AU Capello, F
Scrimin, S
Pillon, M
Carli, M
Bornstein, MH
AF Capello, F.
Scrimin, S.
Pillon, M.
Carli, M.
Bornstein, M. H.
TI COGNITIVE AND MOTOR DEVELOPMENT IN CHILDREN WITH HEMATO-ONCOLOGICAL
DIAGNOSIS IN THE FIRST THREE YEARS OF LIFE: A LONGITUDINAL STUDY
SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
LA Italian
DT Meeting Abstract
CT 36th National Congress of the
Associazione-Italiana-Ematologia-Oncologia-Pediatrica
CY JUN 06-08, 2010
CL Pisa, ITALY
SP Assoc Italiana Ematol Oncol Pediat
C1 [Capello, F.; Pillon, M.; Carli, M.] Univ Padua, Clin Oncoematol Pediat, Dipartimento Pediat, I-35100 Padua, Italy.
[Scrimin, S.] Univ Padua, Dipartimento Psicol Seviluppo Socializzaz, I-35100 Padua, Italy.
[Bornstein, M. H.] NICHHD, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
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 JUN
PY 2010
VL 95
IS 7
SU 1
BP S84
EP S84
PG 1
WC Hematology
SC Hematology
GA 638QO
UT WOS:000280910500179
ER
PT J
AU Gittelsohn, J
Song, HJ
Suratkar, S
Kumar, MB
Henry, EG
Sharma, S
Mattingly, M
Anliker, JA
AF Gittelsohn, Joel
Song, Hee-Jung
Suratkar, Sonali
Kumar, Mohan B.
Henry, Elizabeth G.
Sharma, Sangita
Mattingly, Megan
Anliker, Jean A.
TI An Urban Food Store Intervention Positively Affects Food-Related
Psychosocial Variables and Food Behaviors
SO HEALTH EDUCATION & BEHAVIOR
LA English
DT Article
DE urban; food store program; African American
ID UNITED-STATES; NEIGHBORHOOD CHARACTERISTICS; ENVIRONMENTAL-INFLUENCES;
PHYSICAL-ACTIVITY; AVAILABILITY; OBESITY; PREVALENCE; OVERWEIGHT; ADULTS
AB Obesity and other diet-related chronic diseases are more prevalent in low-income urban areas, which commonly have limited access to healthy foods. The authors implemented an intervention trial in nine food stores, including two supermarkets and seven corner stores, in a low-income, predominantly African American area of Baltimore City, with a comparison group of eight stores in another low-income area of the city. The intervention (Baltimore Healthy Stores; BHS) included an environmental component to increase stocks of more nutritious foods and provided point-of-purchase promotions including signage for healthy choices and interactive nutrition education sessions. Using pre- and postassessments, the authors evaluated the impact of the program on 84 respondents sampled from the intervention and comparison areas. Exposure to intervention materials was modest in the intervention area, and overall healthy food purchasing scores, food knowledge, and self-efficacy did not show significant improvements associated with intervention status. However, based on adjusted multivariate regression results, the BHS program had a positive impact on healthfulness of food preparation methods and showed a trend toward improved intentions to make healthy food choices. Respondents in the intervention areas were significantly more likely to report purchasing promoted foods because of the presence of a BHS shelf label. This is the first food store intervention trial in low-income urban communities to show positive impacts at the consumer level.
C1 [Gittelsohn, Joel] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD 21205 USA.
[Henry, Elizabeth G.] Boston Univ, Boston, MA 02215 USA.
[Sharma, Sangita] Univ N Carolina, Inst Nutr Res, Chapel Hill, NC USA.
[Mattingly, Megan] NIH, Bethesda, MD 20892 USA.
[Anliker, Jean A.] Univ Massachusetts, Amherst, MA 01003 USA.
RP Gittelsohn, J (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, 615 N Wolfe St, Baltimore, MD 21205 USA.
EM jgittels@jhsph.edu
RI Sriwisit, Sukhumaphorn/G-1405-2011;
OI Sharma, Sangita/0000-0002-4995-0010
NR 24
TC 49
Z9 50
U1 3
U2 21
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1090-1981
J9 HEALTH EDUC BEHAV
JI Health Educ. Behav.
PD JUN
PY 2010
VL 37
IS 3
BP 390
EP 402
DI 10.1177/1090198109343886
PG 13
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 600GK
UT WOS:000277972900006
PM 19887625
ER
PT J
AU DiCarlo, AL
Ramakrishnan, N
Hatchett, RJ
AF DiCarlo, Andrea L.
Ramakrishnan, Narayani
Hatchett, Richard J.
TI RADIATION COMBINED INJURY: OVERVIEW OF NIAID RESEARCH
SO HEALTH PHYSICS
LA English
DT Article; Proceedings Paper
CT 12th Coordination and Planning Meeting of the
Radiation-Emergency-Medical-Preparedness-and-Assistance-Network
CY OCT 15-17, 2008
CL Buenos Aires, ARGENTINA
SP Radiat Emergency Med Preparedness & Assistance Network
DE World Health Organization; accidents, nuclear; atomic bomb; emergencies,
radiological
ID MICE; IRRADIATION
AB The term "radiation combined injury" (RCI) is used to describe conditions where radiation injury is coupled with other insults such as burns, wounds, infection, or blunt trauma. A retrospective account of injuries sustained following the atomic bombing of Hiroshima estimates that RCI comprised approximately 65% of all injuries observed. Much of the research that has been performed on RCI was carried out during the Cold War and our understanding of the clinical problem RCI presents does not reflect the latest advances in medicine or science. Because concerns have increased that terrorists might employ radiological or nuclear weapons, and because of the likelihood that victims of such terrorism would experience RCI, the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health sponsored a meeting in 2007 to explore the state of the research in this area, identify programmatic gaps, and establish priorities for future research. As a follow-up to that meeting, in 2008 NIAID sponsored an initiative on RCI, leading to the award of several exploratory/developmental grants, the goals of which are to better understand biological synergy involved in RCI-induced damage, develop improved animal models for various type of RCI, and advance identification and testing of potential countermeasures to treat injuries that would be expected following a radiological or nuclear event. This program has already yielded new insight into the nature of combined injuries and has identified a number of novel and existing compounds that may be effective treatments for this condition. Health Phys. 98(6): 863-867; 2010
C1 [DiCarlo, Andrea L.; Ramakrishnan, Narayani; Hatchett, Richard J.] NIAID, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP DiCarlo, AL (reprint author), NIAID, NIH, Dept Hlth & Human Serv, 6610 Rockledge Dr,Room 5301, Bethesda, MD 20892 USA.
EM cohena@niaid.nih.gov
NR 18
TC 22
Z9 23
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0017-9078
EI 1538-5159
J9 HEALTH PHYS
JI Health Phys.
PD JUN
PY 2010
VL 98
IS 6
BP 863
EP 867
DI 10.1097/HP.0b013e3181a6ee32
PG 5
WC Environmental Sciences; Public, Environmental & Occupational Health;
Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
Imaging
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
GA 595NX
UT WOS:000277619300020
PM 20445395
ER
PT J
AU Hafer, N
Cassatt, D
DiCarlo, A
Ramakrishnan, N
Kaminski, J
Norman, MK
Maidment, B
Hatchett, R
AF Hafer, Nathaniel
Cassatt, David
DiCarlo, Andrea
Ramakrishnan, Narayani
Kaminski, Joseph
Norman, Mai-Kim
Maidment, Bert
Hatchett, Richard
TI NIAID/NIH RADIATION/NUCLEAR MEDICAL COUNTERMEASURES PRODUCT RESEARCH AND
DEVELOPMENT PROGRAM
SO HEALTH PHYSICS
LA English
DT Article; Proceedings Paper
CT 12th Coordination and Planning Meeting of the
Radiation-Emergency-Medical-Preparedness-and-Assistance-Network
CY OCT 15-17, 2008
CL Buenos Aires, ARGENTINA
SP Radiat Emergency Med Preparedness & Assistance Network
DE World Health Organization; blood; dosimetry; gastrointestinal tract
AB One of the greatest national security threats to the United States is the detonation of an improvised nuclear device or a radiological dispersal device in a heavily populated area. The U. S. Government has addressed these threats with a two-pronged strategy of preventing organizations from obtaining weapons of mass destruction and preparing in case an event occurs. The National Institute of Allergy and Infectious Diseases (NIAID) contributes to these preparedness efforts by supporting basic research and development for chemical, biological, radiological, and nuclear countermeasures for civilian use. The Radiation Countermeasures Program at NIAID has established a broad research agenda focused on the development of new medical products to mitigate and treat acute and long-term radiation injury, promote the clearance of internalized radionuclides, and facilitate accurate individual dose and exposure assessment. This paper reviews the recent work and collaborations supported by the Radiation Countermeasures Program. Health Phys. 98(6):903-905;2010
C1 [Hafer, Nathaniel; Cassatt, David; DiCarlo, Andrea; Ramakrishnan, Narayani; Kaminski, Joseph; Norman, Mai-Kim; Maidment, Bert; Hatchett, Richard] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA.
[Hafer, Nathaniel] AAAS Sci & Technol Policy Fellow, Washington, DC 20005 USA.
RP Hatchett, R (reprint author), 6610 Rockledge Dr,Room 5319, Bethesda, MD 20892 USA.
EM hatchettr@niaid.nih.gov
OI Hafer, Nathaniel/0000-0002-0164-5092
NR 5
TC 13
Z9 13
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0017-9078
EI 1538-5159
J9 HEALTH PHYS
JI Health Phys.
PD JUN
PY 2010
VL 98
IS 6
BP 903
EP 905
DI 10.1097/HP.0b013e3181bbc4df
PG 3
WC Environmental Sciences; Public, Environmental & Occupational Health;
Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
Imaging
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
GA 595NX
UT WOS:000277619300028
PM 20445403
ER
PT J
AU Payne, AR
Kellman, P
Anderson, R
McPhaden, AJ
Watkins, S
Schenke, W
Wright, V
Lederman, RJ
Aletras, AH
Arai, AE
Berry, C
AF Payne, A. R.
Kellman, P.
Anderson, R.
McPhaden, A. J.
Watkins, S.
Schenke, W.
Wright, V.
Lederman, R. J.
Aletras, A. H.
Arai, A. E.
Berry, C.
TI 12-WEIGHTED MRI HAS HIGH DIAGNOSTIC ACCURACY FOR MYOCARDIAL HAEMORRHAGE
IN MYOCARDIAL INFARCTION: A PRECLINICAL VALIDATION STUDY IN SWINE
SO HEART
LA English
DT Meeting Abstract
CT Annual Conference and Exhibition of the British-Cardiovascular-Society
CY JUN 07-09, 2010
CL Manchester, ENGLAND
SP British Cardiovasc Soc
C1 [Payne, A. R.; McPhaden, A. J.; Watkins, S.; Berry, C.] Univ Glasgow, Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland.
[Kellman, P.; Anderson, R.; Watkins, S.; Schenke, W.; Lederman, R. J.; Aletras, A. H.; Arai, A. E.] Natl Inst Hlth, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1355-6037
J9 HEART
JI Heart
PD JUN
PY 2010
VL 96
SU 1
BP A42
EP A42
DI 10.1136/hrt.2010.195966.21
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 619JY
UT WOS:000279427700079
ER
PT J
AU Speliotes, EK
Massaro, JM
Hoffmann, U
Vasan, RS
Meigs, JB
Sahani, DV
Hirschhorn, JN
O'Donnell, CJ
Fox, CS
AF Speliotes, Elizabeth K.
Massaro, Joseph M.
Hoffmann, Udo
Vasan, Ramachandran S.
Meigs, James B.
Sahani, Dushyant V.
Hirschhorn, Joel N.
O'Donnell, Christopher J.
Fox, Caroline S.
TI Fatty Liver is Associated With Dyslipidemia and Dysglycemia Independent
of Visceral Fat: The Framingham Heart Study
SO HEPATOLOGY
LA English
DT Article
ID ADIPOSE-TISSUE COMPARTMENTS; INSULIN-RESISTANCE; RISK-FACTORS; METABOLIC
SYNDROME; COMPUTED-TOMOGRAPHY; HEPATIC STEATOSIS; PREVALENCE;
POPULATION; DISEASE; ADULTS
AB Obesity is not uniformly associated with the development of metabolic sequelae. Specific patterns of body fat distribution, in particular fatty liver, may preferentially predispose at-risk individuals to disease. In this study, we characterize the metabolic correlates of fat in the liver in a large community-based sample with and without respect to visceral fat. Fatty liver was measured by way of multidetector computed tomography of the abdomen in 2,589 individuals from the community-based Framingham Heart Study. Logistic and linear regression were used to determine the associations of fatty liver with cardio-metabolic risk factors adjusted for covariates with and without adjustment for other fat depots (body mass index, waist circumference, and visceral adipose tissue). The prevalence of fatty liver was 17%. Compared with participants without fatty liver, individuals with fatty liver had a higher adjusted odds ratio (OR) of diabetes (OR 2.98, 95% confidence interval [CI] 2.12-4.21), metabolic syndrome (OR 5.22, 95% CI 4.15-6.57), hypertension (OR 2.73, 95% CI 2.16-3.44), impaired fasting glucose (OR 2.95, 95% CI 2.32-3.75), insulin resistance (OR 6.16, 95% CI 4.90-7.76); higher triglycerides, systolic blood pressure (SBP), and diastolic blood pressure (DBP); and lower high-density lipoprotein (HDL) and adiponectin levels (P < 0.001 for all). After adjustment for other fat depots, fatty liver remained associated with diabetes, hypertension, impaired fasting glucose, metabolic syndrome, HDL, triglycerides, and adiponectin levels (all P < 0.001), whereas associations with SBP and DBP were attenuated (P > 0.05). Conclusion: Fatty liver is a prevalent condition and is characterized by dysglycemia and dyslipidemia independent of visceral adipose tissue and other obesity measures. This work begins to dissect the specific links between fat depots and metabolic disease. (HEPATOLOGY 2010;51:1979-1987)
C1 [Speliotes, Elizabeth K.] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA.
[Hoffmann, Udo; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA.
[Meigs, James B.] Massachusetts Gen Hosp, Dept Gen Med, Boston, MA 02114 USA.
[Speliotes, Elizabeth K.; Hirschhorn, Joel N.] Broad Inst Harvard, Dept Med & Populat Genet, Cambridge, MA USA.
[Speliotes, Elizabeth K.; Hirschhorn, Joel N.] MIT, Cambridge, MA 02139 USA.
[Massaro, Joseph M.; Vasan, Ramachandran S.; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Massaro, Joseph M.] Boston Univ, Dept Biostat, Boston, MA 02215 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Cardiol, Boston, MA 02118 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02118 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Dept Endocrinol, Boston, MA 02115 USA.
[Hirschhorn, Joel N.] Childrens Hosp, Dept Endocrinol, Boston, MA 02115 USA.
[Hirschhorn, Joel N.] Childrens Hosp, Dept Genet, Boston, MA 02115 USA.
[Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
RP Speliotes, EK (reprint author), Massachusetts Gen Hosp, Dept Gastroenterol, 55 Fruit St, Boston, MA 02114 USA.
EM espeliotes@partners.org
OI Massaro, Joseph/0000-0002-2682-4812; Ramachandran,
Vasan/0000-0001-7357-5970
FU National Institutes of Health [T32 DK07191-32, F32 DK079466-01, K23
DK080145-01]; core contract [N01-HC25195]; American Diabetes
Association; General Clinical Research Centers Program [M01-RR-01066];
National Institute of Diabetes and Digestive and Kidney Diseases [K24
DK080140]
FX E. K S. was supported by National Institutes of Health Grants T32
DK07191-32 (to Daniel K Podolsky in the Department of Gastroenterology
at Massachusetts General Hospital), F32 DK079466-01, and K23
DK080145-01. The Framingham Heart Study is supported by core contract
N01-HC25195. Additional research support was provided by an American
Diabetes Association Career Development Award (to J. B. M.), the General
Clinical Research Centers Program (Grant No. M01-RR-01066), and National
Institute of Diabetes and Digestive and Kidney Diseases Grant K24
DK080140 (to J. B. M.).
NR 34
TC 150
Z9 157
U1 1
U2 10
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD JUN
PY 2010
VL 51
IS 6
BP 1979
EP 1987
DI 10.1002/hep.23593
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 604FB
UT WOS:000278261600015
PM 20336705
ER
PT J
AU Rockey, DC
Seeff, LB
Rochon, J
Freston, J
Chalasani, N
Bonacini, M
Fontana, RJ
Hayashi, PH
AF Rockey, Don C.
Seeff, Leonard B.
Rochon, James
Freston, James
Chalasani, Naga
Bonacini, Maurizio
Fontana, Robert J.
Hayashi, Paul H.
CA US Drug-Induced Liver
TI Causality Assessment in Drug-Induced Liver Injury Using a Structured
Expert Opinion Process: Comparison to the Roussel-Uclaf Causality
Assessment Method
SO HEPATOLOGY
LA English
DT Article
ID UNITED-STATES; ADVERSE REACTIONS; AGREEMENT; SCALE; HEPATOTOXICITY;
PROBABILITY; VALIDATION; HEPATITIS; JUDGMENT; REGISTRY
AB Drug-induced liver injury (DILI) is largely a diagnosis of exclusion and is therefore challenging. The US Drug-Induced Liver Injury Network (DILIN) prospective study used two methods to assess DILI causality: a structured expert opinion process and the Roussel-Uclaf Causality Assessment Method (RUCAM). Causality assessment focused on detailed clinical and laboratory data from patients with suspected DILI. The adjudication process used standardized numerical and descriptive definitions and scored cases as definite, highly likely, probable, possible, or unlikely. Results of the structured expert opinion procedure were compared with those derived by the RUCAM approach. Among 250 patients with suspected DILI, the expert opinion adjudication process scored 78 patients (31%) as definite, 102 (41%) as highly likely, 37 (15%) as probable, 25 (10%) as possible, and 8 (3%) as unlikely. Among 187 enrollees who had received a single implicated drug, initial complete agreement was reached for 50 (27%) with the expert opinion process and for 34 (19%) with a five-category RUCAM scale (P = 0.08), and the two methods demonstrated a modest correlation with each other (Spearman's r = 0.42, P = 0.0001). Importantly, the RUCAM approach substantially shifted the causality likelihood toward lower probabilities in comparison with the DILIN expert opinion process. Conclusion:. The structured DILIN expert opinion process produced higher agreement rates and likelihood scores than RUCAM in assessing causality, but there was still considerable interobserver variability in both. Accordingly, a more objective, reliable, and reproducible means of assessing DILI causality is still needed. (HEPATOLOGY 2010;51:2117-2126)
C1 [Rockey, Don C.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA.
[Seeff, Leonard B.] NIDDK, NIH, Bethesda, MD USA.
[Rochon, James] Duke Clin Res Inst, Durham, NC USA.
[Freston, James] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA.
[Chalasani, Naga] Indiana Univ, Sch Med, Dept Med, Indianapolis, IN USA.
[Bonacini, Maurizio] Calif Pacific Med Ctr, Dept Transplantat, San Francisco, CA USA.
[Fontana, Robert J.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA.
[Hayashi, Paul H.] Univ N Carolina, Sch Med, Liver Program, Div Gastroenterol & Hepatol, Chapel Hill, NC USA.
RP Rockey, DC (reprint author), Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM don.rockey@utsouthwestern.edu
FU National Institutes of Health [U01DK065201, 1U01DK065193, 1U01DK065184,
1U01DK065211, 1U01DK065238, 1U01DK065176]
FX This study was supported by grants U01DK065201, 1U01DK065193,
1U01DK065184, 1U01DK065211, 1U01DK065238, and 1U01DK065176 from the
National Institutes of Health.
NR 28
TC 111
Z9 118
U1 2
U2 4
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD JUN
PY 2010
VL 51
IS 6
BP 2117
EP 2126
DI 10.1002/hep.23577
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 604FB
UT WOS:000278261600029
PM 20512999
ER
PT J
AU Cizza, G
Primma, S
Coyle, M
Gourgiotis, L
Csako, G
AF Cizza, G.
Primma, S.
Coyle, M.
Gourgiotis, L.
Csako, G.
TI Depression and Osteoporosis: A Research Synthesis with Meta-Analysis
SO HORMONE AND METABOLIC RESEARCH
LA English
DT Review
DE bone; fractures; stress; antidepressants; women; evidence-based
medicine; leptin
ID BONE-MINERAL DENSITY; PREMENOPAUSAL WOMEN; MAJOR DEPRESSION;
RISK-FACTOR; POSTMENOPAUSAL WOMEN; OLDER WOMEN; ANOREXIA-NERVOSA; MENTAL
DISTRESS; HIP FRACTURE; FOLLOW-UP
AB Major depressive disorder has been associated with low bone mineral density. The strength of this association, however, varies greatly among studies; the direction of the causative link is still controversial, and the etiology remains unclear. We aimed to confirm this association, assess its magnitude and estimate its clinical relevancy. A total of 535 articles were initially identified and the research synthesis was based on 33 qualified articles. Of these, 25 articles (or 76%) showed an inverse relationship between major depression or minor depression or depressive symptoms and bone mineral density or bone turnover. Meta-analysis could be performed on 20 of the initially selected 33 articles. Standardized weighted differences in mean AP spine, total femur and femoral neck bone mineral density, each from at least 10 studies, were computed in g/cm(2) and transformed into percent differences. At each site, bone mass was lower in subjects with depression as compared to controls: AP spine bone mineral density was 4.73% lower (95% CI -7.28% to -2.19%, p < 0.0001; n = 16 studies), total femur bone mineral density was 3.53% lower (95% CI -5.66% to -1.41%, p < 0.001; n = 13 studies), and femoral neck bone mineral density was 7.32% lower (95% CI -10.67% to -3.96%; p < 0.0005; n = 8 studies). In conclusion, major depressive disorder was associated with lower bone mineral density at the AP spine, femoral neck, and total femur. The deficits in bone mineral density in subjects with depression are of clinical significance and likely to increase fracture risk over the lifetime of these subjects.
C1 [Cizza, G.] NIDDK, CRC, Clin Endocrine Sect, Clin Endocrinol Branch,NIH,DHHS, Bethesda, MD 20892 USA.
[Csako, G.] NIH, Dept Lab Med, Ctr Clin, DHHS, Bethesda, MD 20892 USA.
RP Cizza, G (reprint author), NIDDK, CRC, Clin Endocrine Sect, Clin Endocrinol Branch,NIH,DHHS, Bldg 10,Rm 6-3940, Bethesda, MD 20892 USA.
EM cizzag@intra.niddk.nih.gov
FU National Institute of Diabetes, Digestive, and Kidney Diseases; Warren
Magnuson, National Institutes of Health Clinical Center
FX This study is supported by the Intramural Program of the National
Institute of Diabetes, Digestive, and Kidney Diseases, and the Warren
Magnuson, National Institutes of Health Clinical Center.
NR 64
TC 47
Z9 51
U1 0
U2 5
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0018-5043
J9 HORM METAB RES
JI Horm. Metab. Res.
PD JUN
PY 2010
VL 42
IS 7
BP 467
EP 482
DI 10.1055/s-0030-1252020
PG 16
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 607CC
UT WOS:000278475000001
PM 20455194
ER
PT J
AU Wetherington, CL
AF Wetherington, Cora Lee
TI Sex differences and gonadal hormone influences in drug addiction and
sexual behavior: Progress and possibilities
SO HORMONES AND BEHAVIOR
LA English
DT Editorial Material
C1 NIDA, NIH, Bethesda, MD 20892 USA.
RP Wetherington, CL (reprint author), NIDA, NIH, 6001 Execut Blvd,Room 4282 MSC 9555, Bethesda, MD 20892 USA.
EM cwetheri@nida.nih.gov
NR 0
TC 9
Z9 9
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 0018-506X
J9 HORM BEHAV
JI Horm. Behav.
PD JUN
PY 2010
VL 58
IS 1
BP 2
EP 7
DI 10.1016/j.yhbeh.2010.03.004
PG 6
WC Behavioral Sciences; Endocrinology & Metabolism
SC Behavioral Sciences; Endocrinology & Metabolism
GA 611WN
UT WOS:000278855500002
PM 20211183
ER
PT J
AU Shaw, P
Gogtay, N
Rapoport, J
AF Shaw, Philip
Gogtay, Nitin
Rapoport, Judith
TI Childhood Psychiatric Disorders as Anomalies in Neurodevelopmental
Trajectories
SO HUMAN BRAIN MAPPING
LA English
DT Article
DE magnetic resonance imaging; child development; childhood psychiatric
disorders; modeling
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER;
DEFICIT-HYPERACTIVITY-DISORDER; CORTICAL BRAIN-DEVELOPMENT; ONSET
SCHIZOPHRENIA; DOWNS-SYNDROME; UNAFFECTED SIBLINGS; ADHD; AUTISM;
METAANALYSIS; CHILDREN
AB Childhood psychiatric disorders are rarely static; rather they change over time and longitudinal studies are ideally suited to capture such dynamic processes. Using longitudinal data, insights can be gained into the nature of the perturbation away from the trajectory of typical development in childhood disorders. Thus, some disorders may reflect a delay in neurodevelopmental trajectories. Our studies in children with attention-deficit/hyperactivity disorder (ADHD) suggest that cortical development is delayed with a rightward shift along the age axis in cortical trajectories, most prominent in prefrontal cortical regions. Other disorders may be characterized by differences in the velocity of trajectories: the basic shape of neurodevelopmental curves remains intact, but with disrupted tempo. Thus, childhood onset schizophrenia is associated with a marked increase during adolescence in the velocity of loss of cerebral gray matter. By contrast, in childhood autism there is an early acceleration of brain growth, which overshoots typical dimensions leading to transient cerebral enlargement. Finally, there may be more profound deviations from typical neurodevelopment, with a complete "derailing" of brain growth and a loss of the features which characterize typical brain development. An example is the almost complete silencing of white matter growth during adolescence of patients with childhood onset schizophrenia. Adopting a longitudinal perspective also readily lends itself to the understanding of the neural bases of differential clinical outcomes. Again taking ADHD as an example, we found that remission is associated with convergence to the template of typical development, whereas persistence is accompanied by progressive divergence away from typical trajectories. Plum Brain Mapp 31:917-925,2010. (C) 2010 Wiley-Liss, Inc.
C1 [Shaw, Philip; Gogtay, Nitin; Rapoport, Judith] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA.
RP Shaw, P (reprint author), NIMH, Child Psychiat Branch, Room 3N202,Bldg 10,Ctr Dr, Bethesda, MD 20892 USA.
EM shawp@mail.nih.gov
RI Gogtay, Nitin/A-3035-2008
NR 57
TC 85
Z9 87
U1 4
U2 35
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1065-9471
J9 HUM BRAIN MAPP
JI Hum. Brain Mapp.
PD JUN
PY 2010
VL 31
IS 6
SI SI
BP 917
EP 925
DI 10.1002/hbm.21028
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 605IM
UT WOS:000278341200009
PM 20496382
ER
PT J
AU Xie, JJ
Larochelle, A
Maric, I
Faulhaber, M
Donahue, RE
Dunbar, CE
AF Xie, Jianjun
Larochelle, Andre
Maric, Irina
Faulhaber, Marion
Donahue, Robert E.
Dunbar, Cynthia E.
TI Repetitive Busulfan Administration After Hematopoietic Stem Cell Gene
Therapy Associated with a Dominant HDAC7 Clone in a Nonhuman Primate
SO HUMAN GENE THERAPY
LA English
DT Article
ID II HISTONE DEACETYLASES; ACUTE MYELOID-LEUKEMIA; RETROVIRAL VECTOR;
INSERTIONAL MUTAGENESIS; MOUSE MODEL; IN-VIVO; HISTONE-DEACETYLASE-7;
INTEGRATION; BEHAVIOR; TRANSCRIPTION
AB The risk of genotoxicity of retroviral vector-delivered gene therapy targeting hematopoietic stem cells (HSCs) has been highlighted by the development of clonal dominance and malignancies in human and animal gene therapy trials. Large-animal models have proven invaluable to test the safety of retroviral vectors, but the detection of clonal dominance may require years of follow-up. We hypothesized that hematopoietic stress may accelerate the proliferation and therefore the detection of abnormal clones in these models. We administered four monthly busulfan (Bu) infusions to induce hematopoietic stress in a healthy rhesus macaque previously transplanted with CD34(+) cells transduced with retroviral vectors carrying a simple marker gene. Busulfan administration resulted in significant cytopenias with each cycle, and prolonged pancytopenia after the final cycle with eventual recovery. Before busulfan treatment there was highly polyclonal marking in all lineages. After Bu administration clonal diversity was markedly decreased in all lineages. Unexpectedly, we found no evidence of selection of the MDS1/EVI1 clones present before Bu administration, but a clone with a vector integration in intron 1 of the histone deacetylase-7 (HDAC7) gene became dominant in granulocytes over time after Bu administration. The overall marking level in the animal was increased significantly after Bu treatment and coincident with expansion of the HDAC7 clone, suggesting an in vivo advantage for this clone under stress. HDAC7 expression was upregulated in marrow progenitors containing the vector. Almost 5 years after Bu administration, the animal developed progressive cytopenias, and at autopsy the marrow showed complete lack of neutrophil or platelet maturation, with a new population of approximately 20% undifferentiated blasts. These data suggest that chemotherapeutic stress may accelerate vector-related clonal dominance, even in the absence of drug resistance genes expressed by the vector. This model may both accelerate the detection of abnormal clones to facilitate analysis of genotoxicity for human gene therapy, and help assess the safety of administering myelotoxic chemotherapeutic agents in patients previously engrafted with vector-containing cells.
C1 [Xie, Jianjun; Larochelle, Andre; Faulhaber, Marion; Donahue, Robert E.; Dunbar, Cynthia E.] NHLBI, Mol Hematopoiesis Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Maric, Irina] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Dunbar, CE (reprint author), NHLBI, Mol Hematopoiesis Sect, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM dunbarc@mail.nih.gov
NR 57
TC 3
Z9 3
U1 1
U2 2
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1043-0342
J9 HUM GENE THER
JI Hum. Gene Ther.
PD JUN
PY 2010
VL 21
IS 6
BP 695
EP 703
DI 10.1089/hum.2009.191
PG 9
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 607BC
UT WOS:000278472300008
PM 20102258
ER
PT J
AU Leger, A
Penaud-Budloo, M
Nickerson, ML
Le Guiner, C
Moullier, P
Snyder, RO
AF Leger, Adrien
Penaud-Budloo, Magalie
Nickerson, Michael L.
Le Guiner, Caroline
Moullier, Philippe
Snyder, Richard O.
TI The Rous Sarcoma Virus Promoter Carried by a rAAV Vector Is Resistant to
DNA Methylation in Primate Muscle and Liver
SO HUMAN GENE THERAPY
LA English
DT Meeting Abstract
CT 9th Annual Congress of the French-Society-of-Cell-and-Gene-Therapy
CY JUN 13-15, 2010
CL Paris, FRANCE
SP French Soc Cell & Gene Therapy
C1 [Leger, Adrien; Penaud-Budloo, Magalie; Le Guiner, Caroline; Moullier, Philippe; Snyder, Richard O.] INSERM, UMR649, Inst Rech Therapeut, F-44007 Nantes 1, France.
[Moullier, Philippe; Snyder, Richard O.] Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA.
[Le Guiner, Caroline; Moullier, Philippe] GENETHON, F-91000 Evry, France.
[Snyder, Richard O.] UF Ctr Excellence Regenerat Hlth Biotechnol, Frederick, MD USA.
[Nickerson, Michael L.] NCI, NIH, Human Genet Sect, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1043-0342
J9 HUM GENE THER
JI Hum. Gene Ther.
PD JUN
PY 2010
VL 21
IS 6
BP 776
EP 776
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 607BC
UT WOS:000278472300049
ER
PT J
AU Solomon, BD
Pineda-Alvarez, DE
Raam, MS
Cummings, DAT
AF Solomon, Benjamin D.
Pineda-Alvarez, Daniel E.
Raam, Manu S.
Cummings, Derek A. T.
TI Evidence for inheritance in patients with VACTERL association
SO HUMAN GENETICS
LA English
DT Article
ID MALFORMATIONS
AB VACTERL/VATER association is typically a sporadic disorder. We present data on inheritance in 78 probands with VACTERL association, and show that 9% of probands have a primary relative with at least one component feature of VACTERL association. The prevalence of component features in first-degree relatives is significantly higher than expected in the general population, which has implications for counseling of affected families and for research into possible etiologies.
C1 [Solomon, Benjamin D.; Pineda-Alvarez, Daniel E.; Raam, Manu S.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Raam, Manu S.] Natl Inst Hlth Res Scholars Program, Howard Hughes Med Inst, Bethesda, MD 20892 USA.
[Cummings, Derek A. T.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
RP Solomon, BD (reprint author), NHGRI, Med Genet Branch, NIH, MSC 3717, Bethesda, MD 20892 USA.
EM solomonb@mail.nih.gov
FU Division of Intramural Research, National Human Genome Research
Institute, National Institutes of Health and Human Services, USA
FX The authors would like to express gratitude to the participating
patients and families, and would also like to thank Dr. Maximilian
Muenke for his support and mentorship. This research was supported by
the Division of Intramural Research, National Human Genome Research
Institute, National Institutes of Health and Human Services, USA.
NR 6
TC 29
Z9 33
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
J9 HUM GENET
JI Hum. Genet.
PD JUN
PY 2010
VL 127
IS 6
BP 731
EP 733
DI 10.1007/s00439-010-0814-7
PG 3
WC Genetics & Heredity
SC Genetics & Heredity
GA 596VJ
UT WOS:000277713300013
PM 20369369
ER
PT J
AU Smith, WW
Liu, ZH
Liang, YD
Masuda, N
Swing, DA
Jenkins, NA
Copeland, NG
Troncoso, JC
Pletnikov, M
Dawson, TM
Martin, LJ
Moran, TH
Lee, MK
Borchelt, DR
Ross, CA
AF Smith, Wanli W.
Liu, Zhaohui
Liang, Yideng
Masuda, Naoki
Swing, Debbie A.
Jenkins, Nancy A.
Copeland, Neal G.
Troncoso, Juan C.
Pletnikov, Mikhail
Dawson, Ted M.
Martin, Lee J.
Moran, Timothy H.
Lee, Michael K.
Borchelt, David R.
Ross, Christopher A.
TI Synphilin-1 attenuates neuronal degeneration in the A53T alpha-synuclein
transgenic mouse model
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID CHAPERONE-MEDIATED AUTOPHAGY; LEWY-BODY FORMATION; PARKINSONS-DISEASE;
CELL-DEATH; INTERACTING PROTEIN; INCLUSION FORMATION; MISFOLDED
PROTEINS; BECLIN 1; MICE; MUTATION
AB Genetic alterations in alpha-synuclein cause autosomal dominant familial Parkinsonism and may contribute to sporadic Parkinson's disease (PD). Synphilin-1 is an alpha-synuclein-interacting protein, with implications in PD pathogenesis related to protein aggregation. Currently, the in vivo role of synphilin-1 in alpha-synuclein-linked pathogenesis is not fully understood. Using the mouse prion protein promoter, we generated synphilin-1 transgenic mice, which did not display PD-like phenotypes. However, synphilin-1/A53T alpha-synuclein double-transgenic mice survived longer than A53T alpha-synuclein single-transgenic mice. There were attenuated A53T alpha-synuclein-induced motor abnormalities and decreased astroglial reaction and neuronal degeneration in brains in double-transgenic mice. Overexpression of synphilin-1 decreased caspase-3 activation, increased beclin-1 and LC3 II expression and promoted formation of aggresome-like structures, suggesting that synphilin-1 alters multiple cellular pathways to protect against neuronal degeneration. These studies demonstrate that synphilin-1 can diminish the severity of alpha-synucleinopathy and play a neuroprotective role against A53T alpha-synuclein toxicity in vivo.
C1 [Smith, Wanli W.; Liu, Zhaohui] Univ Maryland, Dept Pharmaceut Sci, Sch Pharm, Baltimore, MD 21201 USA.
[Smith, Wanli W.; Liu, Zhaohui; Liang, Yideng; Masuda, Naoki; Pletnikov, Mikhail; Ross, Christopher A.] Johns Hopkins Univ, Sch Med, Dept Psychiat, Div Neurobiol, Baltimore, MD 21287 USA.
[Pletnikov, Mikhail; Dawson, Ted M.; Ross, Christopher A.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21287 USA.
[Dawson, Ted M.; Ross, Christopher A.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA.
[Troncoso, Juan C.; Martin, Lee J.; Borchelt, David R.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21287 USA.
[Ross, Christopher A.] Johns Hopkins Univ, Sch Med, Dept Pharmacol, Baltimore, MD 21287 USA.
[Dawson, Ted M.] Johns Hopkins Univ, Sch Med, Neuroregenerat Program, Inst Cell Engn, Baltimore, MD 21287 USA.
[Dawson, Ted M.] Johns Hopkins Univ, Sch Med, Stem Cell Program, Inst Cell Engn, Baltimore, MD 21287 USA.
[Pletnikov, Mikhail; Ross, Christopher A.] Johns Hopkins Univ, Sch Med, Cellular & Mol Med Program, Baltimore, MD 21287 USA.
[Moran, Timothy H.] Johns Hopkins Univ, Sch Med, Dept Psychiat, Div Behav Neurosci, Baltimore, MD 21287 USA.
[Swing, Debbie A.; Jenkins, Nancy A.; Copeland, Neal G.] NCI, Mouse Canc Genet Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA.
[Lee, Michael K.] Univ Minnesota, Dept Neurosci, Minneapolis, MN 55455 USA.
RP Smith, WW (reprint author), Univ Maryland, Dept Pharmaceut Sci, Sch Pharm, 20 Penn St, Baltimore, MD 21201 USA.
EM wsmith@rx.umaryland.edu; caross@jhu.edu
RI Lee, Michael/D-9491-2013; Ross, Christopher/H-8395-2013
OI Lee, Michael/0000-0001-5865-9682;
FU NIH [NS38377, RO1NS055252]
FX This work is supported by NIH grant NS38377 and RO1NS055252.
NR 52
TC 43
Z9 43
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD JUN 1
PY 2010
VL 19
IS 11
BP 2087
EP 2098
DI 10.1093/hmg/ddq086
PG 12
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 593IX
UT WOS:000277448500001
PM 20185556
ER
PT J
AU Ban, T
Heymann, JAW
Song, ZY
Hinshaw, JE
Chan, DC
AF Ban, Tadato
Heymann, Juergen A. W.
Song, Zhiyin
Hinshaw, Jenny E.
Chan, David C.
TI OPA1 disease alleles causing dominant optic atrophy have defects in
cardiolipin-stimulated GTP hydrolysis and membrane tubulation
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID DYNAMIN-RELATED GTPASE; MITOCHONDRIAL-DNA; FUSION; MAINTENANCE; PROTEIN;
MGM1
AB The dynamin-related GTPase OPA1 is mutated in autosomal dominant optic atrophy (DOA) (Kjer type), an inherited neuropathy of the retinal ganglion cells. OPA1 is essential for the fusion of the inner mitochondrial membranes, but its mechanism of action remains poorly understood. Here we show that OPA1 has a low basal rate of GTP hydrolysis that is dramatically enhanced by association with liposomes containing negative phospholipids such as cardiolipin. Lipid association triggers assembly of OPA1 into higher order oligomers. In addition, we find that OPA1 can promote the protrusion of lipid tubules from the surface of cardiolipin-containing liposomes. In such lipid protrusions, OPA1 assemblies are observed on the outside of the lipid tubule surface, a protein-membrane topology similar to that of classical dynamins. The membrane tubulation activity of OPA1 is suppressed by GTP gamma S. OPA1 disease alleles associated with DOA display selective defects in several activities, including cardiolipin association, GTP hydrolysis and membrane tubulation. These findings indicate that interaction of OPA1 with membranes can stimulate higher order assembly, enhance GTP hydrolysis and lead to membrane deformation into tubules.
C1 [Song, Zhiyin; Chan, David C.] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA.
[Ban, Tadato; Song, Zhiyin; Chan, David C.] CALTECH, Div Biol, Pasadena, CA 91125 USA.
[Heymann, Juergen A. W.; Hinshaw, Jenny E.] NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA.
RP Chan, DC (reprint author), CALTECH, Howard Hughes Med Inst, 1200 E Calif Blvd,MC114-96, Pasadena, CA 91125 USA.
EM dchan@caltech.edu
FU National Institutes of Health [GM062967]; National Institute of Diabetes
and Digestive and Kidney Diseases; Japan Society for Promotion of
Science (JSPS); Howard Hughes Medical Institute
FX This work was supported by the National Institutes of Health (grant
number GM062967 to D. C. C.) and the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases
(J.E.H.). T. B. was supported by the Japan Society for Promotion of
Science (JSPS) with a Post-Doctoral Fellowship for Research Abroad.
Funding to pay the Open Access publication charges for this article was
provided by the Howard Hughes Medical Institute.
NR 24
TC 77
Z9 77
U1 1
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD JUN 1
PY 2010
VL 19
IS 11
BP 2113
EP 2122
DI 10.1093/hmg/ddq088
PG 10
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 593IX
UT WOS:000277448500003
PM 20185555
ER
PT J
AU Stumpf, JD
Bailey, CM
Spell, D
Stillwagon, M
Anderson, KS
Copeland, WC
AF Stumpf, Jeffrey D.
Bailey, Christopher M.
Spell, Diana
Stillwagon, Matthew
Anderson, Karen S.
Copeland, William C.
TI mip1 containing mutations associated with mitochondrial disease causes
mutagenesis and depletion of mtDNA in Saccharomyces cerevisiae
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID DNA-POLYMERASE-GAMMA; PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; TYPE-1
REVERSE-TRANSCRIPTASE; P55 ACCESSORY SUBUNIT; POLG MUTATIONS; POINT
MUTATIONS; MUTATOR MICE; GENE; DEFECTS; REPLICATION
AB DNA polymerase gamma (pol gamma) is responsible for replication and repair of mitochondrial DNA (mtDNA). Over 150 mutations in POLG (which encodes pol gamma) have been discovered in patients with mitochondrial disorders including Alpers, progressive external ophthalmoplegia and ataxia-neuropathy syndrome. However, the severity and dominance of many POLG disease-associated mutations are unclear, because they have been reported in sporadic cases. To understand the consequences of pol gamma disease-associated mutations in vivo, we identified dominant and recessive changes in mtDNA mutagenesis, depletion and mitochondrial dysfunction caused by 31 mutations in the conserved regions of the gene, MIP1, which encodes the Saccharomyces cerevisiae ortholog of human pol gamma. Twenty mip1 mutant enzymes were shown to disrupt mtDNA replication and may be sufficient to cause disease. Previously uncharacterized sporadic mutations, Q308H, R807C, G1076V, R1096H and S1104C, caused decreased polymerase activity leading to mtDNA depletion and mitochondrial dysfunction. We present evidence showing a limited role of point mutagenesis by these POLG mutations in mitochondrial dysfunction and disease progression. Instead, most mitochondrial defective mip1 mutants displayed reduced or depleted mtDNA. We also determined that the severity of the phenotype of the mip1 mutant strain correlates with the age of onset of disease associated with the human ortholog. Finally, we demonstrated that increasing nucleotide pools by overexpression of ribonucleotide reductase (RNR1) suppressed mtDNA replication defects caused by several dominant mip1 mutations, and the orthologous human mutations revealed severe nucleotide binding defects.
C1 [Stumpf, Jeffrey D.; Spell, Diana; Stillwagon, Matthew; Copeland, William C.] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Bailey, Christopher M.; Anderson, Karen S.] Yale Univ, Dept Pharmacol, New Haven, CT 06520 USA.
RP Copeland, WC (reprint author), NIEHS, Mol Genet Lab, NIH, 111 TW Alexander Dr,Bldg 101,Room E316, Res Triangle Pk, NC 27709 USA.
EM copelan1@niehs.nih.gov
OI Bailey, Chris/0000-0002-5962-9511
FU National Institute of Environmental Health Sciences National Institutes
of Health (NIH) [ES 065078]; NIH [GM49551]; National Institutes of
Health
FX This work was supported by intramural funds from the National Institute
of Environmental Health Sciences National Institutes of Health (NIH) [ES
065078 to W.C.C.]; NIH [GM49551 to K.S.A.] and the National Institutes
of Health Summers of Discovery Program.
NR 58
TC 29
Z9 29
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD JUN 1
PY 2010
VL 19
IS 11
BP 2123
EP 2133
DI 10.1093/hmg/ddq089
PG 11
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 593IX
UT WOS:000277448500004
PM 20185557
ER
PT J
AU Il, LLN
Alur, RP
Boobalan, E
Sergeev, YV
Caruso, RC
Stone, EM
Swaroop, A
Johnson, MA
Brooks, BP
AF Il, Lorenzo L. Nichols
Alur, Ramakrishna P.
Boobalan, Elangovan
Sergeev, Yuri V.
Caruso, Rafael C.
Stone, Edwin M.
Swaroop, Anand
Johnson, Mary A.
Brooks, Brian P.
TI Two Novel CRX Mutant Proteins Causing Autosomal Dominant Leber
Congenital Amaurosis Interact Differently With NRL
SO HUMAN MUTATION
LA English
DT Article
DE cone-rod homeobox; CRX; neural leucine-zipper protein; NRL; Leber
congenital amaurosis; LCA; retinal degeneration
ID TRANSCRIPTION FACTOR NRL; LEUCINE-ZIPPER; HOMEOBOX GENE; RPE65
MUTATIONS; PHOTORECEPTOR; EXPRESSION; HOMEODOMAIN; SEQUENCE;
OPTIMIZATION; CONFORMATION
AB Leber congenital amaurosis (LCA) is a congenital retinal dystrophy characterized by severe visual loss in infancy and nystagmus. Although most often inherited in an autosomal recessive fashion, rare individuals with mutations in the cone-rod homeobox gene, CRX, have dominant disease. CRX is critical for photoreceptor development and acts synergistically with the leucine-zipper transcription factor, NRL. We report on the phenotype of two individuals with LCA due to novel, de novo CRX mutations, c.G264T(p.K88N) and c.413delT(p.I138fs48), that reduce transactivation in vitro to 10% and 30% of control values, respectively. Whereas the c.413delT(p.I138fs48) mutant allows co-expressed NRL to transactivate independently at its normal, baseline level, the c.G264T(p.K88N) mutant reduces co-expressed NRL transactivation and reduces steady state levels of both proteins. Although both mutant proteins predominantly localize normally to the nucleus, they also both show variable cytoplasmic localization. These observations suggest that some CRX-mediated LCA may result from effects beyond haploinsufficiency, such as the mutant protein interefering with other transcription factors' function. Such patients would therefore not likely benefit from a simple, gene-replacement strategy for their disease. (C) 2010 Wiley-Liss, Inc.
C1 [Il, Lorenzo L. Nichols; Alur, Ramakrishna P.; Boobalan, Elangovan; Sergeev, Yuri V.; Caruso, Rafael C.; Brooks, Brian P.] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
[Johnson, Mary A.] Univ Maryland, Dept Ophthalmol & Visual Sci, Baltimore, MD 21201 USA.
[Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
[Stone, Edwin M.] Univ Iowa, Howard Hughes Med Inst, Iowa City, IA 52242 USA.
[Stone, Edwin M.] Univ Iowa, Dept Ophthalmol, Iowa City, IA 52242 USA.
RP Brooks, BP (reprint author), NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bldg 10,Room 10N226,MSC 1860,10 Ctr Dr, Bethesda, MD 20892 USA.
EM brooksb@mail.nih.gov
OI Swaroop, Anand/0000-0002-1975-1141
FU National Eye Institute, National Institutes of Health, U.S. Department
of Health and Human Services; NEI
FX We would like to thank NEI ophthalmic photographers, Denise Cunningham,
Mel Palmer, Mike Bono, and Alicia Zetina for their expert assistance.
This research was sponsored by the intramural program of the National
Eye Institute, National Institutes of Health, U.S. Department of Health
and Human Services. Contract grant sponsor: Intramural Program, NEI. We
would like to thank the staff of the Carver Molecular Diagnostic
Laboratory at the University of Iowa for excellent technical service.
NR 32
TC 0
Z9 0
U1 1
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1059-7794
J9 HUM MUTAT
JI Hum. Mutat.
PD JUN
PY 2010
VL 31
IS 6
BP E1472
EP E1483
DI 10.1002/humu.21268
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA 626QP
UT WOS:000279982200004
ER
PT J
AU Armstrong, A
Nieman, LK
AF Armstrong, A.
Nieman, L. K.
TI Effect of ulipristal acetate, a selective progesterone receptor
modulator (SPRM), on fibroid size in women with symptomatic uterine
fibroids
SO HUMAN REPRODUCTION
LA English
DT Meeting Abstract
CT 26th Annual Meeting of ESHRE
CY JUN 27-30, 2010
CL Rome, ITALY
C1 [Armstrong, A.; Nieman, L. K.] NICHD, Program Reprod & Adult Endocrinol, Bethesda, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0268-1161
J9 HUM REPROD
JI Hum. Reprod.
PD JUN
PY 2010
VL 25
SU 1
BP I90
EP I91
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 625DU
UT WOS:000279875400220
ER
PT J
AU Launer, LJ
Hughes, T
Yu, BB
Masaki, K
Petrovitch, H
Ross, GW
White, LR
AF Launer, Lenore J.
Hughes, Timothy
Yu, Binbing
Masaki, Kamal
Petrovitch, Helen
Ross, G. Webster
White, Lon R.
TI Lowering Midlife Levels of Systolic Blood Pressure as a Public Health
Strategy to Reduce Late-Life Dementia Perspective From the Honolulu
Heart Program/Honolulu Asia Aging Study
SO HYPERTENSION
LA English
DT Article
DE dementia; population-attributable risk; hypertension; older persons;
cohort study; epidemiology
ID CARDIOVASCULAR RISK-FACTORS; JAPANESE-AMERICAN MEN; WHITE-MATTER
LESIONS; ALZHEIMERS-DISEASE; COGNITIVE FUNCTION; HYPERTENSION;
ASSOCIATION; MORTALITY; ATROPHY; COHORT
AB To estimate the potential benefits of lowering systolic blood pressure (SBP) toward preventing late-life dementia, we estimated the population-attributable risk of elevated SBP for dementia. Analyses are based on the cohort of 8006 Japanese American men (born 1900-1919) followed since 1965 as a part of the Honolulu Heart Program, continued as the Honolulu Asia Aging Study. Midlife cardiovascular risk factors and late-life brain function are well described. We estimated the population-attributable risk of dementia cases attributed to midlife SBP, grouped by the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure criteria (<120, 120 to <140, and >= 140 mm Hg), taking into account treatment history, confounding factors, and competitive risk for death. The analysis is based on 7878 subjects, including 491 cases of dementia, with a mean interval of 25 years between measurement of blood pressure and dementia diagnosis. Compared with those with SBP <120 mm Hg, untreated, and <50 years of age at baseline, 17.7% (95% CI: 4.6% to 29.1%) of the cases were attributable to prehypertensive levels (SBP: 120 to >= 140 mm Hg) of SBP, translating into 11 excess cases per 1000. Among those who did not report taking antihypertensive medication in midlife, 27% (95% CI: 8.9% to 42.1%) of dementia cases can be attributed to systolic BP <120 mm Hg, translating into 17 excess cases per 1000. Although population-attributable risk estimates for population subgroups may differ by relative risk for dementia or prevalence of elevated levels of blood pressure, these data suggest that reducing midlife systolic BP is an effective prevention strategy to reduce risk for late-life dementia. (Hypertension. 2010; 55: 1352-1359.)
C1 [Launer, Lenore J.] NIA, LEDB, NIH, Bethesda, MD 20892 USA.
[Masaki, Kamal; Petrovitch, Helen; Ross, G. Webster; White, Lon R.] Pacific Hlth Res Inst, Honolulu, HI USA.
[Masaki, Kamal; Petrovitch, Helen; Ross, G. Webster; White, Lon R.] Univ Hawaii, John A Burns Sch Med, Dept Geriatr Med, Honolulu, HI 96822 USA.
[Petrovitch, Helen; Ross, G. Webster] Univ Hawaii, John A Burns Sch Med, Dept Med, Honolulu, HI 96822 USA.
[Petrovitch, Helen; Ross, G. Webster; White, Lon R.] Kuakini Med Ctr, Honolulu Asia Aging Study, Honolulu, HI USA.
[Ross, G. Webster] Kuakini Med Ctr, Honolulu Dept Vet Affairs, Honolulu, HI USA.
RP Launer, LJ (reprint author), NIA, LEDB, NIH, 7201 Wisconsin Ave,3C-309, Bethesda, MD 20892 USA.
EM launerl@nia.nih.gov
FU National Institute on Aging [1 U01 AG19349, 5 R01 AG017155]
FX This work is supported by National Institute on Aging grants 1 U01
AG19349 and 5 R01 AG017155 and the National Institute on Aging
Intramural Research Program.
NR 45
TC 47
Z9 48
U1 1
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD JUN
PY 2010
VL 55
IS 6
BP 1352
EP U120
DI 10.1161/HYPERTENSIONAHA.109.147389
PG 17
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 598OR
UT WOS:000277848100015
PM 20404223
ER
PT J
AU Wang, XY
Luo, YJ
Escano, CS
Yang, ZW
Asico, L
Li, HW
Jones, JE
Armando, I
Lu, QS
Sibley, DR
Eisner, GM
Jose, PA
AF Wang, Xiaoyan
Luo, Yingjin
Escano, Crisanto S.
Yang, Zhiwei
Asico, Laureano
Li, Hewang
Jones, John E.
Armando, Ines
Lu, Quansheng
Sibley, David R.
Eisner, Gilbert M.
Jose, Pedro A.
TI Upregulation of Renal Sodium Transporters in D(5) Dopamine
Receptor-Deficient Mice
SO HYPERTENSION
LA English
DT Article
DE dopamine; dopamine receptor; knockout mouse; hypertension; sodium
excretion; sodium transporters; AT(1)R blockade
ID ANGIOTENSIN-II TYPE-1; THICK ASCENDING LIMB; LONG-TERM REGULATION; NA-CL
COTRANSPORTER; BLOOD-PRESSURE; KNOCKOUT MICE; GENOME SCAN; RAT-KIDNEY;
HYPERTENSION; EXPRESSION
AB D(5) dopamine receptor (D(5)R)-deficient (D(5)(-/-)) mice have hypertension that is aggravated by an increase in sodium intake. The present experiments were designed to test the hypothesis that a dysregulation of renal sodium transporters is related to the salt sensitivity in D(5)(-/-) mice. D5R was expressed in the renal proximal tubule, thick ascending limb, distal convoluted tubule, and cortical and outer medullary collecting ducts in D(5)(-/-) mice. On a control Na(+) diet, renal protein expressions of NKCC2 (sodium-potassium-2 chloride cotransporter), sodium chloride cotransporter, and alpha and gamma subunits of the epithelial sodium channel were greater in D(5)(-/-) than in D(5)(-/-) mice. Renal renin abundance and urine aldosterone levels were similar but renal angiotensin II type 1 receptor (AT(1)R) protein expression was increased in D(5)(-/-) mice. An elevated Na(+) diet increased further the elevated blood pressure of D(5)(-/-) mice but did not affect the normal blood pressure of D(5)(-/-) mice. The increased levels of NKCC2, sodium chloride cotransporter, and alpha and gamma subunits of the epithelial sodium channel persisted with the elevated Na(+) diet and unaffected by chronic AT1R blockade (losartan) in D(5)(-/-) mice. The expressions of proximal sodium transporters NHE3 (sodium hydrogen exchanger type 3) and NaPi2 (sodium phosphate cotransporter type 2) were increased by the elevated Na(+) diet in D(5)(-/-) mice; the increased expression of NHE3 but not NaPi2 was abolished by AT1R blockade. Our findings suggest that the increased protein expression of sodium transporters/channels in distal nephron segments may be the direct consequence of the disruption of D5R, independent of the renin-angiotensin aldosterone system. (Hypertension. 2010;55:1431-1437.)
C1 [Wang, Xiaoyan; Luo, Yingjin; Escano, Crisanto S.; Asico, Laureano; Li, Hewang; Jones, John E.; Armando, Ines; Lu, Quansheng; Jose, Pedro A.] Georgetown Univ, Sch Med, Childrens Natl Med Ctr, Ctr Mol Physiol Res, Washington, DC 20010 USA.
[Eisner, Gilbert M.] Georgetown Univ, Sch Med, Dept Med, Washington, DC 20010 USA.
[Jose, Pedro A.] Georgetown Univ, Sch Med, Dept Physiol & Biophys, Washington, DC 20010 USA.
[Yang, Zhiwei] Chinese Acad Med Sci, Inst Lab Anim Sci, Beijing 100037, Peoples R China.
[Sibley, David R.] Natl Inst Neurol Disorders & Stroke, Mol Neuropharmacol Sect, NIH, Bethesda, MD USA.
RP Wang, XY (reprint author), Georgetown Univ, Sch Med, Childrens Natl Med Ctr, Ctr Mol Physiol Res, 111 Michigan Ave NW, Washington, DC 20010 USA.
EM xwang@cnmc.org
FU NIH [HL068686, HL023081, HL074940, HL092196,, DK039308]
FX This work was supported by NIH grants HL068686, HL023081, HL074940,
HL092196, and DK039308.
NR 38
TC 16
Z9 20
U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD JUN
PY 2010
VL 55
IS 6
BP 1431
EP 1437
DI 10.1161/HYPERTENSIONAHA.109.148643
PG 7
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 598OR
UT WOS:000277848100026
PM 20404220
ER
PT J
AU Krug, AW
Allenhofer, L
Monticone, R
Spinetti, G
Gekle, M
Wang, MY
Lakatta, EG
AF Krug, Alexander W.
Allenhoefer, Lena
Monticone, Robert
Spinetti, Gaia
Gekle, Michael
Wang, Mingyi
Lakatta, Edward G.
TI Elevated Mineralocorticoid Receptor Activity in Aged Rat Vascular Smooth
Muscle Cells Promotes a Proinflammatory Phenotype via Extracellular
Signal-Regulated Kinase 1/2 Mitogen-Activated Protein Kinase and
Epidermal Growth Factor Receptor-Dependent Pathways
SO HYPERTENSION
LA English
DT Article
DE aldosterone; arterial aging; vascular smooth muscle cells;
mineralocorticoid receptor; inflammation
ID CARDIOVASCULAR-DISEASE ENTERPRISES; ANGIOTENSIN-II; METABOLIC SYNDROME;
MAJOR SHAREHOLDERS; ENDOTHELIAL-CELLS; NADPH OXIDASE; RISK-FACTOR;
ALDOSTERONE; ARTERIAL; EXPRESSION
AB Arterial aging is a predominant risk factor for the onset of cardiovascular diseases, such as hypertension, myocardial infarction, or stroke. Aging is associated with intravascular renin-angiotensin system activation, increased vascular stiffness, intima-media thickening, and a proinflammatory phenotype. Little is known about the influence of aldosterone on arterial aging. Hence, we hypothesized that aldosterone and mineralocorticoid receptor (MR) activation might contribute to and possibly accelerate the arterial aging process. We demonstrate increased MR expression in whole aortae and early passage aortic vascular smooth muscle cells from aged (30 months) compared with adult (8 months) F344XBN rats. Sensitivity to aldosterone-induced extracellular signal-regulated kinase 1/ 2 mitogen-activated protein kinase activity is increased in aged cells. MR blockade and extracellular signal-regulated kinase 1/ 2 mitogen-activated protein kinase inhibition prevent age-associated increases of transforming growth factor-beta, intercellular adhesion molecule 1, and procollagen 1. Aldosterone increases expression of proinflammatory marker proteins, shifting the phenotype of adult vascular smooth muscle cells toward the proinflammatory phenotype of aged rats. Epidermal growth factor receptor expression is increased with age and by aldosterone, and inhibition of epidermal growth factor receptor tyrosine kinase decreases age-associated proinflammatory marker expression. Our data support the hypothesis that increased constitutive MR signaling may promote and amplify age-associated inflammation that accompanies arterial aging through increased angiotensin II-stimulated expression of MR and enhanced sensitivity to aldosterone-mediated extracellular signal-regulated kinase 1/2 activation, likely related to increased epidermal growth factor receptor expression. (Hypertension. 2010; 55: 1476-1483.)
C1 [Krug, Alexander W.] NIA, NIH, Gerontol Res Ctr, Cardiovasc Sci Lab, Baltimore, MD 21224 USA.
[Gekle, Michael] Univ Halle Wittenberg, Julius Bernstein Inst Physiol, Halle, Germany.
RP Krug, AW (reprint author), NIA, NIH, Gerontol Res Ctr, Cardiovasc Sci Lab, Baltimore, MD 21224 USA.
EM awkrug@partners.org
FU National Institutes of Health National Institute on Aging Intramural
Research Program; Deutsche Forschungsgemeinschaft [KR 3337/2-1]
FX This research was supported by the National Institutes of Health
National Institute on Aging Intramural Research Program and the Deutsche
Forschungsgemeinschaft (KR 3337/2-1 to A.W.K.).
NR 54
TC 50
Z9 50
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
EI 1524-4563
J9 HYPERTENSION
JI Hypertension
PD JUN
PY 2010
VL 55
IS 6
BP 1476
EP U349
DI 10.1161/HYPERTENSIONAHA.109.148783
PG 18
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 598OR
UT WOS:000277848100032
PM 20421514
ER
PT J
AU Kamalakannan, S
Gururajan, A
Sari-Sarraf, H
Long, R
Antani, S
AF Kamalakannan, Sridharan
Gururajan, Arunkumar
Sari-Sarraf, Hamed
Long, Rodney
Antani, Sameer
TI Double-Edge Detection of Radiographic Lumbar Vertebrae Images Using
Pressurized Open DGVF Snakes
SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
LA English
DT Article
DE Directional gradient vector flow (DGVF) snakes; double edges; energy
minimization; lumbar vertebrae; pressure force
ID GRADIENT VECTOR FLOW; ACTIVE CONTOUR MODELS; CHEST RADIOGRAPHS;
FRACTURES
AB The detection of double edges in X-ray images of lumbar vertebrae is of prime importance in the assessment of vertebral injury or collapse that may be caused by osteoporosis and other spine pathology. In addition, if the above double-edge detection process is conducted within an automatic framework, it would not only facilitate inexpensive and fast means of obtaining objective morphometric measurements on the spine, but also remove the human subjectivity involved in the morphometric analysis. This paper proposes a novel force-formulation scheme, termed as pressurized open directional gradient vector flow snakes, to discriminate and detect the superior and inferior double edges present in the radiographic images of the lumbar vertebrae. As part of the validation process, this algorithm is applied to a set of 100 lumbar images and the detection results are quantified using analyst-generated ground truth. The promising nature of the detection results bears testimony to the efficacy of the proposed approach.
C1 [Kamalakannan, Sridharan; Gururajan, Arunkumar; Sari-Sarraf, Hamed] Texas Tech Univ, Lubbock, TX 79415 USA.
[Long, Rodney; Antani, Sameer] NIH, Bethesda, MD 20892 USA.
RP Kamalakannan, S (reprint author), Texas Tech Univ, Lubbock, TX 79415 USA.
EM sridharan.kamalakannan@ttu.edu; arunkumar.gururajan@ttu.edu;
hamed.sari-sarraf@ttu.edu; rlong@mail.nih.gov; santani@mail.nih.gov
OI Antani, Sameer/0000-0002-0040-1387; Kamalakannan,
Sridharan/0000-0003-4106-9728
FU Intramural NIH HHS
NR 26
TC 5
Z9 5
U1 0
U2 0
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0018-9294
J9 IEEE T BIO-MED ENG
JI IEEE Trans. Biomed. Eng.
PD JUN
PY 2010
VL 57
IS 6
BP 1325
EP 1334
DI 10.1109/TBME.2010.2040082
PG 10
WC Engineering, Biomedical
SC Engineering
GA 597PL
UT WOS:000277770600008
PM 20172792
ER
PT J
AU Ratta, B
Nautiyal, B
Ravindra, PV
Chaturvedi, U
Kumar, S
Subudhi, PK
Chindera, K
Tiwari, S
Barman, NN
Tiwari, AK
AF Ratta, Barkha
Nautiyal, Binita
Ravindra, P. V.
Chaturvedi, Uttara
Kumar, Sudesh
Subudhi, P. K.
Chindera, Kantaraja
Tiwari, Sangeeta
Barman, N. N.
Tiwari, Ashok K.
TI Characterization and Expression of E2 Glycoprotein of Classical Swine
Fever Virus in a Eukaryotic Expression System
SO INDIAN JOURNAL OF VIROLOGY
LA English
DT Article
DE Classical swine fever (CSF); Classical swine fever virus (CSFV); Reverse
transcription-polymerase chain reaction (RT-PCR)
ID NEWCASTLE-DISEASE VIRUS; N-LINKED GLYCOSYLATION; DNA; PROTEIN;
IMMUNIZATION; PROTECTION; CHALLENGE; INDUCTION; INFECTION; APOPTOSIS
AB Classical swine fever (CSF) is an economically important Office International des Epizooties (OIE) list A disease of swine characterized by high fever and multiple haemmorhages. The E2 glycoprotein of CSFV is immunogenic and induces neutralizing antibodies against CSFV. In the present study, complete coding region of the E2 gene from Indian virulent field isolate (Mathura) was amplified by reverse transcription-polymerase chain reaction (RTPCR) and subsequently cloned into a mammalian expression vector; pcDNA3.1(+) at BamHI and XbaI site. The recombinant plasmid; pcDNA.E2.CSFV. was confirmed by restriction enzyme digestion. The pcDNA.E2.CSFV. transfected Vero cell expressed E2 protein which was confirmed by western blotting, immunoperoxidase and indirect immunofluorescent tests. Additionally, flow cytometry analysis also confirmed that 15% of transfected Vero cells expressed the E2 glycoprotein compared to mock or vector alone transfected cells. Further study is under way to evaluate recombinant pcDNA.E2.CSFV. Mathura clone as DNA vaccine against CSFV.
C1 [Chaturvedi, Uttara; Kumar, Sudesh; Subudhi, P. K.; Chindera, Kantaraja; Barman, N. N.; Tiwari, Ashok K.] Indian Vet Res Inst, Mol Biol Lab, Div Anim Biotechnol, Izatnagar 243122, Uttar Pradesh, India.
[Ratta, Barkha] Indian Vet Res Inst, Immunochem Lab, Dept Biochem, Izatnagar 243122, Uttar Pradesh, India.
[Nautiyal, Binita; Tiwari, Sangeeta] MJP Rohilkhand Univ, Dept Anim Sci, Bareilly 243006, Uttar Pradesh, India.
[Ravindra, P. V.] NCI, NIH, Bethesda, MD 20892 USA.
RP Tiwari, AK (reprint author), Indian Vet Res Inst, Mol Biol Lab, Div Anim Biotechnol, Izatnagar 243122, Uttar Pradesh, India.
EM aktiwari63@yahoo.com
OI Ravindra, P V/0000-0003-4228-1843
FU ICAR
FX Authors wish to thank the Director, Indian Veterinary Research
Institute, Izatnagar 243 122 (UP) for providing necessary facilities to
carry out the work and ICAR for providing financial Assistance under
AP-Cess Scheme.
NR 26
TC 1
Z9 1
U1 0
U2 2
PU INDIAN VIROLOGICAL SOC
PI HISAR
PA CCS HARYANA AGRICULTURAL UNIV, DEPT PLANT PATHOLOGY, HISAR, 125 004,
INDIA
SN 0970-2822
J9 INDIAN J VIROL
JI Indian J. Virol.
PD JUN
PY 2010
VL 21
IS 1
BP 69
EP 75
DI 10.1007/s13337-010-0009-9
PG 7
WC Virology
SC Virology
GA 690IZ
UT WOS:000284998300011
PM 23637481
ER
PT J
AU Bestor, A
Stewart, PE
Jewett, MW
Sarkar, A
Tilly, K
Rosa, PA
AF Bestor, Aaron
Stewart, Philip E.
Jewett, Mollie W.
Sarkar, Amit
Tilly, Kit
Rosa, Patricia A.
TI Use of the Cre-lox Recombination System To Investigate the lp54 Gene
Requirement in the Infectious Cycle of Borrelia burgdorferi
SO INFECTION AND IMMUNITY
LA English
DT Article
ID LYME-DISEASE SPIROCHETE; LINEAR PLASMIDS 1P25; FORMING PROTEIN P13;
HUMAN-FACTOR-H; CIRCULAR PLASMID; SURFACE PROTEIN; SENSU-STRICTO;
MAMMALIAN HOST; STRAIN B31; RESISTANCE
AB Borrelia burgdorferi, the causative agent of Lyme disease, has a complex genome consisting of a linear chromosome and up to 21 linear and circular plasmids. These plasmids encode numerous proteins critical to the spirochete's infectious cycle and many hypothetical proteins whose functions and requirements are unknown. The conserved linear plasmid lp54 encodes several proteins important for survival in the mouse-tick infectious cycle, but the majority of the proteins are of unknown function and lack homologs outside the borreliae. In this study we adapted the Cre-lox recombination system to create large deletions in the B. burgdorferi genome. Using Cre-lox, we systematically investigated the contribution of 14 adjacent genes on the left arm of lp54 to the overall infectivity of B. burgdorferi. The deletion of the region of lp54 encompassing bba07 to bba14 had no significant effect on the infectious cycle of B. burgdorferi. The deletion of bba01 to bba07 resulted in a slight growth defect but did not significantly affect the ability of B. burgdorferi to complete the infectious cycle. This study demonstrated the utility of the Cre-lox system to efficiently explore gene requirements in B. burgdorferi and surprisingly revealed that a large number of the highly conserved proteins encoded on lp54 are not required to complete the infectious cycle.
C1 [Bestor, Aaron; Stewart, Philip E.; Jewett, Mollie W.; Sarkar, Amit; Tilly, Kit; Rosa, Patricia A.] NIAID, Lab Zoonot Pathogens, NIH, Rocky Mt Labs, Hamilton, MT 59840 USA.
RP Bestor, A (reprint author), NIAID, Lab Zoonot Pathogens, NIH, Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA.
EM bestora@niaid.nih.gov
FU NIH NIAID
FX This research was supported by the Intramural Research Program of the
NIH NIAID.
NR 59
TC 16
Z9 16
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
J9 INFECT IMMUN
JI Infect. Immun.
PD JUN
PY 2010
VL 78
IS 6
BP 2397
EP 2407
DI 10.1128/IAI.01059-09
PG 11
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 598ML
UT WOS:000277841300005
PM 20231410
ER
PT J
AU Card, JW
Carey, MA
Voltz, JW
Bradbury, JA
Ferguson, CD
Cohen, EA
Schwartz, S
Flake, GP
Morgan, DL
Arbes, SJ
Barrow, DA
Barros, SP
Offenbacher, S
Zeldin, DC
AF Card, Jeffrey W.
Carey, Michelle A.
Voltz, James W.
Bradbury, J. Alyce
Ferguson, Catherine D.
Cohen, Eric A.
Schwartz, Samuel
Flake, Gordon P.
Morgan, Daniel L.
Arbes, Samuel J., Jr.
Barrow, David A.
Barros, Silvana P.
Offenbacher, Steven
Zeldin, Darryl C.
TI Modulation of Allergic Airway Inflammation by the Oral Pathogen
Porphyromonas gingivalis
SO INFECTION AND IMMUNITY
LA English
DT Article
ID FETAL-GROWTH RESTRICTION; CORONARY-HEART-DISEASE; FUNGAL MICROBIOTA;
DEFICIENT MICE; MURINE MODEL; ASTHMA; HYPERRESPONSIVENESS; INFECTION;
RESPONSES; INCREASE
AB Accumulating evidence suggests that bacteria associated with periodontal disease may exert systemic immunomodulatory effects. Although the improvement in oral hygiene practices in recent decades correlates with the increased incidence of asthma in developed nations, it is not known whether diseases of the respiratory system might be influenced by the presence of oral pathogens. The present study sought to determine whether subcutaneous infection with the anaerobic oral pathogen Porphyromonas gingivalis exerts a regulatory effect on allergic airway inflammation. BALB/c mice sensitized and subsequently challenged with ovalbumin exhibited airway hyperresponsiveness to methacholine aerosol and increased airway inflammatory cell influx and Th2 cytokine (interleukin-4 [IL-4], IL-5, and IL-13) content relative to those in nonallergic controls. Airway inflammatory cell and cytokine contents were significantly reduced by establishment of a subcutaneous infection with P. gingivalis prior to allergen sensitization, whereas serum levels of ovalbumin-specific IgE and airway responsiveness were not altered. Conversely, subcutaneous infection initiated after allergen sensitization did not alter inflammatory end points but did reduce airway responsiveness in spite of increased serum IgE levels. These data provide the first direct evidence of a regulatory effect of an oral pathogen on allergic airway inflammation and responsiveness. Furthermore, a temporal importance of the establishment of infection relative to allergen sensitization is demonstrated for allergic outcomes.
C1 [Card, Jeffrey W.; Carey, Michelle A.; Voltz, James W.; Bradbury, J. Alyce; Ferguson, Catherine D.; Cohen, Eric A.; Schwartz, Samuel; Flake, Gordon P.; Morgan, Daniel L.; Arbes, Samuel J., Jr.; Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
[Barrow, David A.; Barros, Silvana P.; Offenbacher, Steven] Univ N Carolina, Sch Dent, Dept Periodontol, Chapel Hill, NC USA.
[Barrow, David A.; Barros, Silvana P.; Offenbacher, Steven] Univ N Carolina, Sch Dent, Ctr Oral & Syst Dis, Chapel Hill, NC USA.
RP Zeldin, DC (reprint author), NIEHS, Div Intramural Res, NIH, 111 TW Alexander Dr,Bldg 101,Room A222, Res Triangle Pk, NC 27709 USA.
EM zeldin@niehs.nih.gov
FU NIH, National Institute of Environmental Health Sciences [Z01 ES025043];
University of North Carolina General Clinical Research Center
[Mp1-RR-00046]; American Lung Association of North Carolina; National
Institute of Environmental Health Sciences Inhalation Facility
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Environmental Health Sciences (grant no. Z01
ES025043 to D.C.Z.), by a grant (Mp1-RR-00046) from the University of
North Carolina General Clinical Research Center (S.O.), and by a Senior
Research Training Fellowship from the American Lung Association of North
Carolina (J.W.C.). This research was conducted in part at the National
Institute of Environmental Health Sciences Inhalation Facility under
contract to Alion Science and Technology.
NR 37
TC 8
Z9 8
U1 0
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
J9 INFECT IMMUN
JI Infect. Immun.
PD JUN
PY 2010
VL 78
IS 6
BP 2488
EP 2496
DI 10.1128/IAI.01270-09
PG 9
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 598ML
UT WOS:000277841300014
PM 20308298
ER
PT J
AU Taylor, LD
Nelson, DE
Dorward, DW
Whitmire, WM
Caldwell, HD
AF Taylor, Lacey D.
Nelson, David E.
Dorward, David W.
Whitmire, William M.
Caldwell, Harlan D.
TI Biological Characterization of Chlamydia trachomatis Plasticity Zone
MACPF Domain Family Protein CT153
SO INFECTION AND IMMUNITY
LA English
DT Article
ID OBLIGATE INTRACELLULAR PATHOGEN; GAMMA IMMUNE EVASION; PORE-FORMING
TOXINS; GENOME SEQUENCE; LISTERIA-MONOCYTOGENES; MEMBRANE-ATTACK;
HOST-CELL; DEPENDENT CYTOLYSINS; INFECTION TROPISM; HUMAN-COMPLEMENT
AB Chlamydia trachomatis strains are obligate intracellular human pathogens that share near genomic synteny but have distinct infection and disease organotropisms. The genetic basis for differences in the pathogen-host relationship among chlamydial strains is linked to a variable region of chlamydial genomes, termed the plasticity zone (PZ). Two groups of PZ-encoded proteins, the membrane attack complex/perforin (MACPF) domain protein (CT153) and members of the phospholipase D-like (PLD) family, are related to proteins that modify membranes and lipids, but the functions of CT153 and the PZ PLDs (pzPLDs) are unknown. Here, we show that full-length CT153 (p91) was present in the elementary bodies (EBs) of 15 C. trachomatis reference strains. CT153 underwent a rapid infection-dependent proteolytic cleavage into polypeptides of 57 and 41 kDa that was independent of de novo chlamydial protein synthesis. Following productive infection, p91 was expressed during the mid-developmental cycle and was similarly processed into p57 and p41 fragments. Infected-cell fractionation studies showed that insoluble fractions contained p91, p57, and p41, whereas only p91 was found in the soluble fraction, indicating that unprocessed CT153 may be secreted. Finally, CT153 localized to a distinct population of reticulate bodies, some of which were in contact with the inclusion membrane.
C1 [Taylor, Lacey D.; Whitmire, William M.; Caldwell, Harlan D.] NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Dorward, David W.] NIAID, Res Technol Branch, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Nelson, David E.] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
RP Caldwell, HD (reprint author), NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA.
EM hcaldwell@niaid.nih.gov
FU NIH, NIAID
FX This research was supported by the Intramural Research Program of the
NIH, NIAID.
NR 60
TC 18
Z9 18
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
J9 INFECT IMMUN
JI Infect. Immun.
PD JUN
PY 2010
VL 78
IS 6
BP 2691
EP 2699
DI 10.1128/IAI.01455-09
PG 9
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 598ML
UT WOS:000277841300032
PM 20351143
ER
PT J
AU Tilahun, ME
Rajagopalan, G
Shah-Mahoney, N
Lawlor, RG
Tilahun, AY
Xie, C
Natarajan, K
Margulies, DH
Ratner, DI
Osborne, BA
Goldsby, RA
AF Tilahun, Mulualem E.
Rajagopalan, Govindarajan
Shah-Mahoney, Nalini
Lawlor, Rebecca G.
Tilahun, Ashenafi Y.
Xie, Chen
Natarajan, Kannan
Margulies, David H.
Ratner, David I.
Osborne, Barbara A.
Goldsby, Richard A.
TI Potent Neutralization of Staphylococcal Enterotoxin B by Synergistic
Action of Chimeric Antibodies
SO INFECTION AND IMMUNITY
LA English
DT Article
ID TOXIC-SHOCK-SYNDROME; POLYSPECIFIC IMMUNOGLOBULIN-G;
TUMOR-NECROSIS-FACTOR; II TRANSGENIC MICE; T-CELL-ACTIVATION; BACTERIAL
SUPERANTIGENS; INTRAVENOUS IMMUNOGLOBULIN; LETHAL SHOCK;
MONOCLONAL-ANTIBODY; STREPTOCOCCAL SUPERANTIGENS
AB Staphylococcal enterotoxin B (SEB), a shock-inducing exotoxin synthesized by Staphylococcus aureus, is an important cause of food poisoning and is a class B bioterrorism agent. SEB mediates antigen-independent activation of a major subset of the T-cell population by cross-linking T-cell receptors (TCRs) with class II major histocompatibility complex (MHC-II) molecules of antigen-presenting cells, resulting in the induction of antigen independent proliferation and cytokine secretion by a significant fraction of the T-cell population. Neutralizing antibodies inhibit SEB-mediated T-cell activation by blocking the toxin's interaction with the TCR or MHC-II and provide protection against the debilitating effects of this superantigen. We derived and searched a set of monoclonal mouse anti-SEB antibodies to identify neutralizing anti-SEB antibodies that bind to different sites on the toxin. A pair of non-cross-reactive, neutralizing anti-SEB monoclonal antibodies (MAbs) was found, and a combination of these antibodies inhibited SEB-induced T-cell proliferation in a synergistic rather than merely additive manner. In order to engineer antibodies more suitable than mouse MAbs for use in humans, the genes encoding the VL and VH gene segments of a synergistically acting pair of mouse MAbs were grafted, respectively, onto genes encoding the constant regions of human Ig kappa and human IgG1, transfected into mammalian cells, and used to generate chimeric versions of these antibodies that had affinity and neutralization profiles essentially identical to their mouse counterparts. When tested in cultures of human peripheral blood mononuclear cells or splenocytes derived from HLA-DR3 transgenic mice, the chimeric human-mouse antibodies synergistically neutralized SEB-induced T-cell activation and cytokine production.
C1 [Tilahun, Mulualem E.; Shah-Mahoney, Nalini; Xie, Chen; Ratner, David I.; Goldsby, Richard A.] Amherst Coll, Dept Biol, Amherst, MA 01002 USA.
[Tilahun, Mulualem E.; Lawlor, Rebecca G.; Osborne, Barbara A.; Goldsby, Richard A.] Univ Massachusetts, Dept Vet & Anim Sci, Amherst, MA 01003 USA.
[Rajagopalan, Govindarajan; Tilahun, Ashenafi Y.] Mayo Clin, Coll Med, Dept Immunol, Rochester, MN 55905 USA.
[Natarajan, Kannan; Margulies, David H.] NIAID, Mol Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Goldsby, RA (reprint author), Amherst Coll, Dept Biol, 423 McGuire Life Sci Bldg, Amherst, MA 01002 USA.
EM ragoldsby@amherst.edu
RI Margulies, David/H-7089-2013;
OI Margulies, David/0000-0001-8530-7375
FU National Institutes of Health [AI057652, AI076944, AI68741]
FX This study was supported by National Institutes of Health grants
AI057652, AI076944, and AI68741.
NR 53
TC 21
Z9 23
U1 0
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
J9 INFECT IMMUN
JI Infect. Immun.
PD JUN
PY 2010
VL 78
IS 6
BP 2801
EP 2811
DI 10.1128/IAI.01121-09
PG 11
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 598ML
UT WOS:000277841300042
PM 20308304
ER
PT J
AU Mineo, TWP
Oliveira, CJF
Silva, DAO
Oliveira, LL
Abatepaulo, AR
Ribeiro, DP
Ferreira, BR
Mineo, JR
Silva, JS
AF Mineo, Tiago W. P.
Oliveira, Carlo J. F.
Silva, Deise A. O.
Oliveira, Leandro L.
Abatepaulo, Antonio R.
Ribeiro, Damaso P.
Ferreira, Beatriz R.
Mineo, Jose R.
Silva, Joao S.
TI Neospora caninum excreted/secreted antigens trigger CC-chemokine
receptor 5-dependent cell migration
SO INTERNATIONAL JOURNAL FOR PARASITOLOGY
LA English
DT Article
DE Neospora caninum; Excreted/secreted antigens; Monocytes; Dendritic
cells; Cell migration
ID HOST-PARASITE RELATIONSHIP; GUT EPITHELIAL MONOLAYERS; IMMATURE
DENDRITIC CELLS; CD4(+) T-CELLS; TOXOPLASMA-GONDII; BONE-MARROW;
APICOMPLEXAN PARASITES; GAMMA-INTERFERON; INFECTION; PROTEINS
AB Neospora caninum, the causative agent of neosporosis, is an obligate intracellular parasite considered to be a major cause of abortion in cattle throughout the world. Most studies concerning N. caninum have focused on life cycle, seroepidemiology, pathology and vaccination, while data on host-parasite interaction, such as host cell migration, mechanisms of evasion and dissemination of this parasite during the early phase of infection are still poorly understood. Here we show the ability of excreted/secreted antigens from N. caninum (NcESAs) to attract monocytic cells to the site of primary infection in both in vitro and in vivo assays. Molecules from the family of cyclophilins present on the NcESAs were shown to work as chemokine-like proteins and NcESA-induced chemoattraction involved G(i) protein signaling and participation of CC-chemokine receptor 5 (CCR5). Additionally, we demonstrate the ability of NcESAs to enhance the expression of CCR5 on monocytic cells and this increase occurred in parallel with the chemotactic activity of NcESAs by increasing cell migration. These results suggest that during the first days of infection, N. caninum produces molecules capable of inducing monocytic cell migration to the sites of infection, which will consequently enhance initial parasite invasion and proliferation. Altogether, these results help to clarify some key features involved in the process of cell migration and may reveal virulence factors and therapeutic targets to control neosporosis. (C) 2010 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.
C1 [Mineo, Tiago W. P.; Oliveira, Carlo J. F.; Oliveira, Leandro L.; Abatepaulo, Antonio R.; Silva, Joao S.] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Biochem & Immunol, Sao Paulo, Brazil.
[Mineo, Tiago W. P.; Silva, Deise A. O.; Ribeiro, Damaso P.; Mineo, Jose R.] Univ Fed Uberlandia, Inst Biomed Sci, BR-38400902 Uberlandia, MG, Brazil.
[Oliveira, Carlo J. F.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Ferreira, Beatriz R.] USP, Sch Nursing Ribeirao Preto, Dept Maternal Child Nursing & Publ Hlth, BR-14040902 Ribeirao Preto, SP, Brazil.
RP Mineo, TWP (reprint author), Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Biochem & Immunol, Sao Paulo, Brazil.
EM tiago.mineo@pq.cnpq.br
RI Mineo, Tiago/B-4153-2009; Silva, Joao/A-4484-2008; Ferreira,
Beatriz/C-2003-2012; Mineo, Jose/B-4151-2009; Oliveira,
Leandro/D-3616-2009
OI Mineo, Tiago/0000-0002-2339-2743; Ferreira, Beatriz/0000-0002-6781-2236;
Mineo, Jose/0000-0002-9010-7228; Oliveira, Leandro/0000-0003-4353-7011
FU CNPq [473178/2007-9]; FAPESP [2006/06803-4]
FX The authors thank Walter M. Turato and Cristiane M. Milanezi for
technical assistance and NIAID intramural editor Brenda Rae Marshall.
This work was supported by Brazilian funding agencies CNPq
(473178/2007-9) and FAPESP (2006/06803-4).
NR 61
TC 7
Z9 7
U1 0
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0020-7519
J9 INT J PARASITOL
JI Int. J. Parasit.
PD JUN
PY 2010
VL 40
IS 7
BP 797
EP 805
DI 10.1016/j.ijpara.2009.12.003
PG 9
WC Parasitology
SC Parasitology
GA 608LQ
UT WOS:000278586000005
PM 20060395
ER
PT J
AU Perez, P
Rowzee, AM
Zheng, CY
Adriaansen, J
Baum, BJ
AF Perez, Paola
Rowzee, Anne M.
Zheng, Changyu
Adriaansen, Janik
Baum, Bruce J.
TI Salivary epithelial cells: An unassuming target site for gene
therapeutics
SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
LA English
DT Article
DE Salivary glands; Gene therapeutics; Viral vectors; Protein sorting
ID TRANSGENIC SECRETORY PROTEINS; PAROTID-GLANDS; SUBMANDIBULAR-GLANDS;
ACINAR-CELLS; HORMONE; MOUSE; PATHWAYS; VECTOR
AB Salivary glands are classical exocrine glands whose external secretions result in the production of saliva However, in addition to the secretion of exocrine proteins, salivary epithelial cells are also capable of secreting proteins internally, into the bloodstream This brief review examines the potential for using salivary epithelial cells as a target site for in situ gene transfer. with an ultimate goal of producing therapeutic proteins for treating both systemic and upper gastrointestinal tract disorders The review discusses the protein secretory pathways reported to be present in salivary epithelial cells, the viral gene transfer vectors shown useful for transducing these cells, model transgenic secretory proteins examined, and some clinical conditions that might benefit from such salivary gland gene transfer. Published by Elsevier Ltd
C1 [Perez, Paola; Rowzee, Anne M.; Zheng, Changyu; Adriaansen, Janik; Baum, Bruce J.] NIDCR, MPTB, NIH, Bethesda, MD 20892 USA.
RP Baum, BJ (reprint author), NIDCR, MPTB, NIH, Bldg 10,Room 1N113,MSC 1190,10 Ctr Dr, Bethesda, MD 20892 USA.
OI Rowzee, Anne/0000-0003-1969-9133
FU National Institute of Dental and Craniofacial Research
FX The authors' research was supported by the Intramural Research Program
of the National Institute of Dental and Craniofacial Research.
NR 28
TC 17
Z9 17
U1 0
U2 1
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 JUN
PY 2010
VL 42
IS 6
BP 773
EP 777
DI 10.1016/j.biocel.2010.02.012
PG 5
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 606IO
UT WOS:000278417700001
PM 20219693
ER
PT J
AU Arias, HR
Rosenberg, A
Targowska-Duda, KM
Feuerbach, D
Jozwiak, K
Moaddel, R
Wainer, IW
AF Arias, Hugo R.
Rosenberg, Avraham
Targowska-Duda, Katarzyna M.
Feuerbach, Dominik
Jozwiak, Krzysztof
Moaddel, Ruin
Wainer, Irving W.
TI Tricyclic antidepressants and mecamylamine bind to different sites in
the human alpha 4 beta 2 nicotinic receptor ion channel
SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
LA English
DT Article
DE Nicotinic acetylcholine receptors; Tricyclic antidepressants;
Mecamylamine; Conformational states; Thermodynamic parameters; Molecular
modeling
ID ACETYLCHOLINE-RECEPTORS; AFFINITY-CHROMATOGRAPHY; MOLECULAR-MECHANISMS;
NONCOMPETITIVE INHIBITORS; ANTI-DEPRESSANTS; ALPHA-3-BETA-4;
ANTAGONISTS; IMIPRAMINE; CELLS; DYNAMICS
AB The interaction of tricyclic antidepressants with the human (h) alpha 4 beta 2 nicotinic acetylcholine receptor in different conformational states was compared with that for the noncompetitive antagonist mecamylamine by using functional and structural approaches The results established that (a) [(3)H]imipramine binds to h alpha 4 beta 2 receptors with relatively high affinity (K(d) = 0.83 +/- 0.08 mu M), but imipramine does not differentiate between the desensitized and resting states, (b) although tricyclic antidepressants inhibit (+/-)-epibatidine-induced Ca(2+) influx in HEK293-h alpha 4 beta 2 cells with potencies that are in the same concentration range as that for (+/-)-mecamylamine, tricyclic antidepressants inhibit [(3)H]imipramine binding to h alpha 4 beta 2 receptors with affinities >100-fold higher than that for (+/-)-mecamylamine This can be explained by our docking results where imipramine interacts with the leucine (position 9') and valine (position 13') rings by van der Waals contacts, whereas mecamylamine interacts electrostatically with the outer ring (position 20'), (c) van der Waals interactions are in agreement with the thermodynamic results, indicating that imipramine interacts with the desensitized and resting receptors by a combination of enthalpic and entropic components. However, the entropic component is more Important in the desensitized state, suggesting local conformational changes In conclusion, our data indicate that tricyclic antidepressants and mecamylamine efficiently inhibit the ion channel by interacting at different lumina! sites The high proportion of protonated mecamylamine calculated at physiological pH suggests that this drug can be attracted to the channel mouth before binding deeper within the receptor ion channel finally blocking ion flux (C) 2010 Elsevier Ltd All rights reserved
C1 [Arias, Hugo R.] Midwestern Univ, Coll Pharm, Dept Pharmaceut Sci, Glendale, AZ 85308 USA.
[Rosenberg, Avraham; Moaddel, Ruin; Wainer, Irving W.] NIA, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA.
[Targowska-Duda, Katarzyna M.; Jozwiak, Krzysztof] Med Univ Lublin, Dept Chem, Lublin, Poland.
[Feuerbach, Dominik] Novartis Inst Biomed Res, Basel, Switzerland.
RP Arias, HR (reprint author), Midwestern Univ, Coll Pharm, Dept Pharmaceut Sci, 19555 N 59th Ave, Glendale, AZ 85308 USA.
RI Targowska-Duda, Katarzyna/I-3434-2016
FU Science Foundation Arizona; Stardust Foundation; College of Pharmacy,
Midwestern University; Polish Ministry of Science and Higher Education
[NN 405297036]; Foundation for Polish Science; NIH, National Institute
on Aging
FX This research was supported by grants from the Science Foundation
Arizona and Stardust Foundation and the College of Pharmacy, Midwestern
University (to H.R.A.), and by grants from the Polish Ministry of
Science and Higher Education (No NN 405297036) and FOCUS and
TEAM research subsidy from the Foundation for Polish Science (to K J.).
This research was also supported in part by the Intramural Research
Program of the NIH, National Institute on Aging. The authors thank to
Paula lacoban for her technical assistance.
NR 44
TC 21
Z9 21
U1 0
U2 0
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 JUN
PY 2010
VL 42
IS 6
BP 1007
EP 1018
DI 10.1016/j.biocel.2010.03.002
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 606IO
UT WOS:000278417700029
PM 20223294
ER
PT J
AU Colpe, LJ
Barker, PR
Karg, RS
Batts, KR
Morton, KB
Gfroerer, JC
Stolzenberg, SJ
Cunningham, DB
First, MB
Aldworth, J
AF Colpe, Lisa J.
Barker, Peggy R.
Karg, Rhonda S.
Batts, Kathy R.
Morton, Katherine B.
Gfroerer, Joseph C.
Stolzenberg, Stephanie J.
Cunningham, David B.
First, Michael B.
Aldworth, Jeremy
TI The National Survey on Drug Use and Health Mental Health Surveillance
Study: calibration study design and field procedures
SO INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH
LA English
DT Article
DE calibration; K6; Mental Health Surveillance Study
ID SUBSTANCE USE DISORDERS; AXIS-I; DIAGNOSES; INTERVIEW; RELIABILITY;
VALIDITY; ILLNESS
AB The Mental Health Surveillance Study (MHSS) is an ongoing initiative by the Substance Abuse and Mental Health Services Administration (SAMHSA) to monitor the prevalence of serious mental illness (SMI) among adults in the USA. In 2008, the MHSS used data from clinical interviews to calibrate mental health data from the National Survey on Drug Use and Health (NSDUH) for estimating the prevalence of SMI based on the full NSDUH sample. The clinical interview used was the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV; SCID). NSDUH interviews were administered via audio computer-assisted self-interviewing (ACASI) to a nationally representative sample of the population aged 12 years or older. A total of 46 180 NSDUH interviews were completed with adults aged 18 years or older in 2008. The SCID was administered by mental health clinicians to a sub-sample of 1506 adults via telephone. This paper describes the MHSS calibration study procedures, including information on sample selection, instrumentation, follow-up, data quality protocols, and management of distressed respondents. Copyright (c) 2010 John Wiley & Sons, Ltd.
C1 [Colpe, Lisa J.; Barker, Peggy R.; Gfroerer, Joseph C.] Subst Abuse & Mental Hlth Serv Adm, Off Appl Studies, Rockville, MD USA.
[Karg, Rhonda S.; Batts, Kathy R.; Morton, Katherine B.; Stolzenberg, Stephanie J.; Cunningham, David B.; Aldworth, Jeremy] RTI Int, Res Triangle Pk, NC USA.
[First, Michael B.] Columbia Univ, Coll Phys & Surg, New York, NY USA.
[First, Michael B.] New York State Psychiat Inst & Hosp, Biometr Res Dept, New York, NY 10032 USA.
RP Colpe, LJ (reprint author), NIMH, 6001 Execut Blvd, Bethesda, MD 20892 USA.
EM Lisa.Colpe@NIH.gov
FU Division of Population Surveys, Office of Applied Studies, Substance
Abuse and Mental Health Services Administration, US Department of Health
and Human Services; RTI International [283-2004-00022]
FX This work was prepared by the Division of Population Surveys, Office of
Applied Studies, Substance Abuse and Mental Health Services
Administration, US Department of Health and Human Services, and by RTI
International (a trade name of Research Triangle Institute). Work by RTI
was performed under Contract No. 283-2004-00022. The authors thank Mary
Ellen Marsden for her helpful review.
NR 26
TC 11
Z9 11
U1 2
U2 9
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 1049-8931
J9 INT J METH PSYCH RES
JI Int. J. Methods Psychiatr. Res.
PD JUN
PY 2010
VL 19
SU 1
BP 36
EP 48
DI 10.1002/mpr.311
PG 13
WC Psychiatry
SC Psychiatry
GA 610MJ
UT WOS:000278736700004
PM 20527004
ER
PT J
AU Novak, SP
Colpe, LJ
Barker, PR
Gfroerer, JC
AF Novak, Scott P.
Colpe, Lisa J.
Barker, Peggy R.
Gfroerer, Joseph C.
TI Development of a brief mental health impairment scale using a nationally
representative sample in the USA
SO INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH
LA English
DT Article
DE impairment; item response theory; mental health; World Health
Organization Disability Assessment Schedule
ID COMORBIDITY-SURVEY; UNITED-STATES; DISORDERS; PREVALENCE; ILLNESS
AB A psychometric analysis was conducted to reduce the number of items needed to assess the disability associated with mental disorders using the World Health Organization Disability Assessment Schedule (WHODAS). The WHODAS was to be used in the Substance Abuse and Mental Health Services Administration National Survey on Drug Use and Health (NSDUH), beginning in 2008, as part of a screening algorithm to produce estimates of the prevalence of serious mental illness (SMI) in the US adult population. The goal of the work presented in this paper was to create a parsimonious screening scale from the full 16-item WHODAS that was administered to 24 156 respondents (aged 18+) in the 2002 NSDUH. Exploratory factor analysis showed that WHODAS responses were unidimensional. A two-parameter polytomous Item Response Theory model showed that all 16 WHODAS items had good item discrimination (slopes greater than 1.0) for each response option. Analysis of item difficulties and differential item function across socio-demographic categories was then used to select a subset of eight items to create a short version of the WHODAS. The Pearson correlation between scores in the original 16-item and reduced eight-item WHODAS scales was 0.97, documenting that the vast majority of variation in total scale scores was retained in the reduced scale. Copyright (c) 2010 John Wiley & Sons, Ltd.
C1 [Novak, Scott P.] RT Int, Res Triangle Pk, NC USA.
[Colpe, Lisa J.; Barker, Peggy R.; Gfroerer, Joseph C.] Subst Abuse & Mental Hlth Serv Adm, Off Appl Studies, Rockville, MD USA.
RP Colpe, LJ (reprint author), NIMH, 6001 Execut Blvd, Bethesda, MD 20892 USA.
EM Lisa.Colpe@NIH.GOV
FU Division of Population Surveys, Office of Applied Studies, Substance
Abuse and Mental Health Services Administration, US Department of Health
and Human Services; RTI International [283-2004-00022]
FX This work was prepared by the Division of Population Surveys, Office of
Applied Studies, Substance Abuse and Mental Health Services
Administration, US Department of Health and Human Services, and by RTI
International (a trade name of Research Triangle Institute). Work by RTI
was performed under Contract No. 283-2004-00022.
NR 24
TC 14
Z9 14
U1 2
U2 5
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 1049-8931
J9 INT J METH PSYCH RES
JI Int. J. Methods Psychiatr. Res.
PD JUN
PY 2010
VL 19
SU 1
BP 49
EP 60
DI 10.1002/mpr.313
PG 12
WC Psychiatry
SC Psychiatry
GA 610MJ
UT WOS:000278736700005
PM 20527005
ER
PT J
AU Aldworth, J
Colpe, LJ
Gfroerer, JC
Novak, SP
Chromy, JR
Barker, PR
Barnett-Walker, K
Karg, RS
Morton, KB
Spagnola, K
AF Aldworth, Jeremy
Colpe, Lisa J.
Gfroerer, Joseph C.
Novak, Scott P.
Chromy, James R.
Barker, Peggy R.
Barnett-Walker, Kortnee
Karg, Rhonda S.
Morton, Katherine B.
Spagnola, Katherine
TI The National Survey on Drug Use and Health Mental Health Surveillance
Study: calibration analysis
SO INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH
LA English
DT Article
DE calibration; Mental Health Surveillance Study; serious mental illness
AB The Mental Health Surveillance Study (MHSS) is an ongoing initiative by the Substance Abuse and Mental Health Services Administration to develop and implement methods for measuring the prevalence of serious mental illness (SMI) among adults in the USA. The 2008 MHSS used data from clinical interviews administered to a sub-sample of respondents to calibrate mental health screening scale data from the National Survey on Drug Use and Health (NSDUH) for estimating the prevalence of SMI in the full NSDUH sample. The mental health scales included the K6 screening scale of psychological distress (administered to all respondents) along with two measures of functional impairment (each administered to a random half-sample of respondents): the World Health Organization Disability Assessment Schedule (WHODAS) and the Sheehan Disability Scale (SDS). The Structured Clinical Interview for DSM-IV (SCID) was administered to a sub-sample of 1506 adult NSDUH respondents within 4 weeks of completing the NSDUH interview. Results indicate that while SMI prediction accuracy of the K6 is improved by adding either the WHODAS or the SDS to the prediction equation, the models with the WHODAS are more robust. The results of the calibration study and methods used to derive prevalence estimates of SMI are presented. Copyright (c) 2010 John Wiley & Sons, Ltd.
C1 [Aldworth, Jeremy; Novak, Scott P.; Chromy, James R.; Barnett-Walker, Kortnee; Karg, Rhonda S.; Morton, Katherine B.; Spagnola, Katherine] RTI Int, Res Triangle Pk, NC USA.
[Colpe, Lisa J.; Gfroerer, Joseph C.; Barker, Peggy R.] Subst Abuse & Mental Hlth Serv Adm, Off Appl Studies, Rockville, MD USA.
RP Colpe, LJ (reprint author), NIMH, 6001 Execut Blvd, Bethesda, MD 20892 USA.
EM Lisa.Colpe@NIH.gov
FU Division of Population Surveys, Office of Applied Studies, Substance
Abuse and Mental Health Services Administration, US Department of Health
and Human Services; RTI International [283-2004-00022]
FX This work was prepared by the Division of Population Surveys, Office of
Applied Studies, Substance Abuse and Mental Health Services
Administration, US Department of Health and Human Services, and by RTI
International (a trade name of Research Triangle Institute). Work by RTI
was performed under Contract No. 283-2004-00022.
NR 6
TC 20
Z9 20
U1 0
U2 6
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 1049-8931
J9 INT J METH PSYCH RES
JI Int. J. Methods Psychiatr. Res.
PD JUN
PY 2010
VL 19
SU 1
BP 61
EP 87
DI 10.1002/mpr.312
PG 27
WC Psychiatry
SC Psychiatry
GA 610MJ
UT WOS:000278736700006
PM 20527006
ER
PT J
AU Hansson, AC
Nixon, K
Rimondini, R
Damadzic, R
Sommer, WH
Eskay, R
Crews, FT
Heilig, M
AF Hansson, Anita C.
Nixon, Kimberly
Rimondini, Roberto
Damadzic, Ruslan
Sommer, Wolfgang H.
Eskay, Robert
Crews, Fulton T.
Heilig, Markus
TI Long-term suppression of forebrain neurogenesis and loss of neuronal
progenitor cells following prolonged alcohol dependence in rats
SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE Adult neurogenesis; animal model; alcoholism; immunohistochemistry;
plasticity
ID NEURAL STEM-CELLS; HIPPOCAMPAL NEUROGENESIS; ADULT NEUROGENESIS; DENTATE
GYRUS; CELLULAR COMPOSITION; ETHANOL-CONSUMPTION; OLFACTORY DEFICITS;
ANIMAL-MODEL; BRAIN; PROLIFERATION
AB Alcohol dependence leads to persistent neuroadaptations, potentially related to structural plasticity. Previous work has shown that hippocampal neurogenesis is modulated by alcohol, but effects of chronic alcohol on neurogenesis in the forebrain subventricular zone (SVZ) have not been reported. Effects in this region may be relevant for the impairments in olfactory discrimination present in alcoholism. Here, we examined the effects of prolonged alcohol dependence on neurogenesis. Rats were sacrificed directly after 7 wk of intermittent alcohol vapour exposure, or 3, 7 or 21 d into abstinence. Proliferation was assessed using BrdU and Ki67 immunoreactivity, newly differentiated neurons (neurogenesis) as doublecortin-immunoreactivity (DCX-IR), and neural stem cells using the SOX2 marker. In the dentate gyrus, chronic dependence resulted in a pattern similar to that previously reported for acute alcohol exposure: proliferation and neurogenesis were suppressed by the end of exposure, rebounded on day 3 of abstinence, and returned to control levels by days 7 and 21. In the SVZ, proliferation was also suppressed at the end of alcohol exposure, followed by a proliferation burst 3 d into abstinence. However, in this area, there was a trend for reduced proliferation on days 7 and 21 of abstinence, and this was accompanied by significant suppression of DCX-IR, indicating a long-term suppression of forebrain neurogenesis. Finally, a decrease in the SOX2 stem cell marker was detected at days 7 and 21, suggesting long-term reduction of the SVZ stem cell pool. While suppression of hippocampal neurogenesis by alcohol dependence is transient, the suppression in the forebrain SVZ appears long-lasting.
C1 [Hansson, Anita C.; Damadzic, Ruslan; Sommer, Wolfgang H.; Eskay, Robert; Heilig, Markus] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
[Nixon, Kimberly] Univ Kentucky, Dept Pharmaceut Sci, Lexington, KY USA.
[Rimondini, Roberto] Univ Bologna, Dept Pharmacol, I-40126 Bologna, Italy.
[Crews, Fulton T.] Univ N Carolina, Bowles Ctr Alcohol Studies, Chapel Hill, NC USA.
RP Heilig, M (reprint author), NIAAA, Lab Clin & Translat Studies, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM markus.heilig@mail.nih.gov
RI Nixon, Kimberly/A-1217-2015;
OI Heilig, Markus/0000-0003-2706-2482; roberto,
rimondini/0000-0003-4099-513X; Sommer, Wolfgang/0000-0002-5903-6521
FU NIAAA
FX Supported by NIAAA Intramural Program.
NR 54
TC 31
Z9 31
U1 1
U2 4
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1461-1457
J9 INT J NEUROPSYCHOPH
JI Int. J. Neuropsychopharmacol.
PD JUN
PY 2010
VL 13
IS 5
BP 583
EP 593
DI 10.1017/S1461145710000246
PG 11
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 611BN
UT WOS:000278785600004
PM 20334723
ER
PT J
AU Ingram, DD
Mussolino, ME
AF Ingram, D. D.
Mussolino, M. E.
TI Weight loss from maximum body weight and mortality: the Third National
Health and Nutrition Examination Survey Linked Mortality File
SO INTERNATIONAL JOURNAL OF OBESITY
LA English
DT Article
DE follow-up studies; longitudinal studies; proportional hazards models;
men; women
ID ALL-CAUSE MORTALITY; AGED 40-64 YEARS; US ADULTS; LONG-TERM; MASS INDEX;
OLD-AGE; OVERWEIGHT; COHORT; OBESITY; MEN
AB Objective: The aim of this longitudinal study is to examine the relationship between weight loss from maximum body weight, body mass index (BMI), and mortality in a nationally representative sample of men and women.
Design: Longitudinal cohort study.
Subjects: In all, 6117 whites, blacks, and Mexican-Americans 50 years and over at baseline who survived at least 3 years of follow-up, from the Third National Health and Nutrition Examination Survey Linked Mortality Files (1988-1994 with passive mortality follow-up through 2000), were included.
Measurements: Measured body weight and self-reported maximum body weight obtained at baseline. Weight loss (maximum body weight minus baseline weight) was categorized as <5%, 5-<15%, and >= 15%. Maximum BMI (reported maximum weight (kg)/measured baseline height (m)(2)) was categorized as healthy weight (18.5-24.9), overweight (25.0-29.9), and obese (>= 30.0).
Results: In all, 1602 deaths were identified. After adjusting for age, race, smoking, health status, and preexisting illness, overweight men with weight loss of 15% or more, overweight women with weight loss of 5-<15%, and women in all BMI categories with weight loss of 15% or more were at increased risk of death from all causes compared with those in the same BMI category who lost <5%; hazard ratios ranged from 1.46 to 2.70. Weight loss of 5-<15% reduced risk of death from cardiovascular diseases among obese men.
Conclusions: Weight loss of 15% or more from maximum body weight is associated with increased risk of death from all causes among overweight men and among women regardless of maximum BMI. International Journal of Obesity (2010) 34, 1044-1050; doi:10.1038/ijo.2010.41; published online 9 March 2010
C1 [Ingram, D. D.] Ctr Dis Control & Prevent, Off Anal & Epidemiol, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA.
[Mussolino, M. E.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
RP Ingram, DD (reprint author), Ctr Dis Control & Prevent, Off Anal & Epidemiol, Natl Ctr Hlth Stat, 3311 Toledo Rd,Room 6211, Hyattsville, MD 20782 USA.
EM ddingram@cdc.gov
NR 32
TC 25
Z9 25
U1 0
U2 1
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 JUN
PY 2010
VL 34
IS 6
BP 1044
EP 1050
DI 10.1038/ijo.2010.41
PG 7
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 609NM
UT WOS:000278663500012
PM 20212495
ER
PT J
AU Van Waes, C
Allen, CT
Citrin, D
Gius, D
Colevas, AD
Harold, NA
Rudy, S
Nottingham, L
Muir, C
Chen, Z
Singh, AK
Dancey, J
Morris, JC
AF Van Waes, Carter
Allen, Clint T.
Citrin, Deborah
Gius, David
Colevas, A. Dimetrios
Harold, Nancy A.
Rudy, Susan
Nottingham, Liesl
Muir, Christine
Chen, Zhong
Singh, Anurag K.
Dancey, Janet
Morris, John C.
TI MOLECULAR AND CLINICAL RESPONSES IN A PILOT STUDY OF GEFITINIB WITH
PACLITAXEL AND RADIATION IN LOCALLY ADVANCED HEAD-AND-NECK CANCER
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
DE Epidermal growth factor receptor; Head and neck cancer; Gefitinib;
Paclitaxel; Radiation
ID GROWTH-FACTOR-RECEPTOR; SQUAMOUS-CELL CARCINOMA; NF-KAPPA-B; ZD1839
IRESSA; CYTOTOXIC AGENTS; TYROSINE KINASE; SIGNAL PATHWAYS; LUNG-CANCER;
IN-VIVO; EXPRESSION
AB Purpose: Epidermal growth factor receptor (EGFR) overexpression in head-and-neck squamous cell carcinoma (HNSCC) stimulates tumor cell proliferation, inhibits apoptosis, and increases chemotherapy and radiation resistance. We examined the toxicity, safety and the effects on EGFR signaling in tumor biopsy samples from patients with locally advanced HNSCC treated with the EGFR signaling inhibitor gefitinib (GEF) combined with weekly intravenous paclitaxel (PAC) and radiation therapy (RT).
Methods and Materials: This was a pilot Phase I dose-escalation study. Eligibility included Stage III to IVB HNSCC, age >= 18 years, no prior RT or chemotherapy, adequate organ function, and informed consent. Endpoints included determination of maximum tolerated dose (MTD) and analysis of treatment effect on EGER signaling, tumor cell proliferation, and apoptosis in biopsy samples.
Results: Ten patients were treated. The MTD of this combination was GEF 250 mg/d with PAC 36 mg/m(2) intravenously weekly x 6 with concurrent RT. Grade 3/4 toxicities included prolonged (>8 weeks) stomatitis (7 patients), infection (2 patients), and interstitial pneumonitis (1 patient). There were five complete responses (CR) and two partial responses (PR). Of 7 patients undergoing serial biopsies, only 1 patient demonstrated a reduction in phosphorylated ECM, decreased downstream signaling, and reduced cellular proliferation after initiating GEE.
Conclusions: Inhibition of EGFR by GEE was observed in only one of seven tumors studied. The addition of GEE to PAC and RT did not appear to improve the response of locally advanced HNSCC compared with our prior experience with PAC and RT alone. This treatment appeared to delay recovery from stomatitis. (C) 2010 Elsevier Inc.
C1 [Van Waes, Carter; Allen, Clint T.; Rudy, Susan; Nottingham, Liesl; Chen, Zhong] NIDCD, Head & Neck Surg Branch, NIH, Bethesda, MD USA.
[Van Waes, Carter; Citrin, Deborah; Gius, David; Singh, Anurag K.] NCI, Radiat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Colevas, A. Dimetrios; Dancey, Janet] NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Harold, Nancy A.; Muir, Christine; Morris, John C.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Morris, JC (reprint author), Mark O Hatfield Clin Res Ctr, Room 4-5330,10 Ctr Dr, Bethesda, MD 20892 USA.
EM jmorris@mail.nih.gov
FU National Cancer Institute; National Institute of Deafness and
Communication Disorders [Z01-DC-000016, Z01-DC-000073]; AstraZeneca
Pharmaceuticals
FX This work was supported by grants from the Intramural Research Program
of the Center for Cancer Research, National Cancer Institute; the
National Institute of Deafness and Communication Disorders Projects
Z01-DC-000016 and Z01-DC-000073; and a Clinical Trials Agreement with
AstraZeneca Pharmaceuticals.
NR 37
TC 20
Z9 20
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD JUN 1
PY 2010
VL 77
IS 2
BP 447
EP 454
DI 10.1016/j.ijrobp.2009.05.037
PG 8
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 602VR
UT WOS:000278167500018
PM 19879702
ER
PT J
AU Belfer, I
Wu, TX
Hipp, H
Walter, J
Scully, M
Nyquist, PA
Bollettino, A
Goldman, D
Max, MB
DeGraba, TJ
AF Belfer, Inna
Wu, Tianxia
Hipp, Heather
Walter, Joan
Scully, Michele
Nyquist, Paul A.
Bollettino, Antonella
Goldman, David
Max, Mitchell B.
DeGraba, Thomas J.
TI Linkage of large-vessel carotid atherosclerotic stroke to inflammatory
genes via a systematic screen
SO INTERNATIONAL JOURNAL OF STROKE
LA English
DT Article
DE atherosclerosis; haplotype; immune genes; inflammatory; single
nucleotide polymorphism; stroke
ID INTERLEUKIN-1-BETA POLYMORPHISM -511; ISCHEMIC-STROKE;
MYOCARDIAL-INFARCTION; ENDOTHELIAL-CELLS; RISK PROFILE; ASSOCIATION;
PROCOAGULANT; DISEASE; ENDARTERECTOMY; POPULATION
AB Background
Inflammatory cytokines including the IL-1 family, TNF-alpha and IL-6 mediate the formation of thrombosis on the luminal surface of atherosclerotic plaques. Gene polymorphisms that regulate these cytokines' expression may explain part of the variation in susceptibility to stroke in patients with carotid atherosclerosis. The aim of this study was to evaluate the role of single-nucleotide polymorphisms (SNPs) and haplotypes in inflammatory genes as they relate to symptomatic carotid atherosclerosis.
Methods
The study included 95 subjects with symptomatic (transient ischaemic attacks or stroke) and 113 subjects with asymptomatic carotid atherosclerotic disease. A panel of evenly spaced SNPs including previously reported functionally significant polymorphisms were genotyped for IL-1 beta (10 SNPs), IL-1 alpha (nine SNPs), IL-1RN (11 SNPs), IL-6 (seven SNPs) and TNF-alpha and TNF-beta (seven SNPs).
Results
Using single SNP analysis, IL-1RN rs315934 (P=0 center dot 025), IL-1RN rs315946 (P=0 center dot 042), IL-1RN rs315921 (P=0 center dot 035), IL-6 rs1180243 (P=0 center dot 018) and IL-1 alpha rs2071373 (P=0 center dot 025) were associated with decreased odds of symptomatic carotid disease. Additionally, two diplotypes of the IL-1RN gene (P=0 center dot 023 and 0 center dot 0064) and one diplotype in the IL-1 alpha gene (P=0 center dot 02) were associated with a protective affect from cerebral ischaemic events. Logistic analysis for interaction of the protective SNPs reveals an additive effect of all SNP pair combinations.
Conclusion
These results suggest that genetic polymorphisms in proinflammatory genes may contribute to interindividual differences in the development of symptomatic carotid atherosclerotic disease.
C1 [Walter, Joan; DeGraba, Thomas J.] Natl Naval Med Ctr, Dept Neurol, Bethesda, MD 20889 USA.
[Belfer, Inna; Wu, Tianxia; Hipp, Heather; Scully, Michele; Bollettino, Antonella; Max, Mitchell B.] Natl Inst Dent & Craniofacial Res, NIH, DHHS, Bethesda, MD USA.
[Belfer, Inna; Hipp, Heather; Bollettino, Antonella; Goldman, David] NIAAA, Neurogenet Lab, NIH, DHHS, Rockville, MD 20852 USA.
[Walter, Joan; DeGraba, Thomas J.] Uniformed Serv Univ Hlth Sci, Dept Neurol, Bethesda, MD USA.
[Nyquist, Paul A.] Johns Hopkins, Baltimore, MD USA.
RP DeGraba, TJ (reprint author), Natl Naval Med Ctr, Dept Neurol, Bldg 9,2nd Deck,8901 Wisconsin Ave, Bethesda, MD 20889 USA.
EM tjdegraba@bethesda.med.navy.mil
RI Goldman, David/F-9772-2010;
OI Goldman, David/0000-0002-1724-5405; Hipp, Heather/0000-0002-1089-3928
FU NIH [Z01 DE00366, Z01 AA000301]; Henry Jackson Foundation [USUHS
G192BR-C4]
FX Funding: Supported by the NIH Intramural Grants Z01 DE00366 and Z01
AA000301, and the Comprehensive Neuroscience Program Grant USUHS
G192BR-C4 (Henry Jackson Foundation).
NR 35
TC 4
Z9 5
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1747-4930
J9 INT J STROKE
JI Int. J. Stroke
PD JUN
PY 2010
VL 5
IS 3
BP 145
EP 151
DI 10.1111/j.1747-4949.2010.00422.x
PG 7
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 592WF
UT WOS:000277411600002
PM 20536609
ER
PT J
AU Merino, MJ
AF Merino, Maria J.
TI What Is New in Renal Pathology?
SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article; Proceedings Paper
CT 2nd International Pathology Meeting 2010
CY MAY 21-29, 2010
CL Santiago, CHILE
ID CELL CARCINOMA; PROLIFERATION
C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Merino, MJ (reprint author), NCI, Ctr Canc Res, Bldg 10,Room 2N212, Bethesda, MD 20892 USA.
EM mjmerino@mail.nih.gov
NR 7
TC 4
Z9 5
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1066-8969
J9 INT J SURG PATHOL
JI Int. J. Surg. Pathol.
PD JUN
PY 2010
VL 18
IS 3
SU S
BP 98S
EP 100S
DI 10.1177/1066896910370469
PG 3
WC Pathology; Surgery
SC Pathology; Surgery
GA 595IZ
UT WOS:000277605200017
PM 20484271
ER
PT J
AU Merino, MJ
AF Merino, Maria J.
TI Malignant Mesothelioma Mimicking Ovarian Cancer
SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article; Proceedings Paper
CT 2nd International Pathology Meeting 2010
CY MAY 21-29, 2010
CL Santiago, CHILE
ID PERITONEAL MESOTHELIOMA; MURAL NODULES; TUMORS
C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Merino, MJ (reprint author), NCI, Ctr Canc Res, Bldg 10,Room 2N212, Bethesda, MD 20892 USA.
EM mjmerino@mail.nih.gov
NR 12
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1066-8969
J9 INT J SURG PATHOL
JI Int. J. Surg. Pathol.
PD JUN
PY 2010
VL 18
IS 3
SU S
BP 178S
EP 180S
DI 10.1177/1066896910370880
PG 3
WC Pathology; Surgery
SC Pathology; Surgery
GA 595IZ
UT WOS:000277605200033
PM 20484287
ER
PT J
AU Zou, J
Le, D
Thoma, GR
AF Zou, Jie
Le, Daniel
Thoma, George R.
TI Locating and parsing bibliographic references in HTML medical articles
SO INTERNATIONAL JOURNAL ON DOCUMENT ANALYSIS AND RECOGNITION
LA English
DT Article; Proceedings Paper
CT 16th Document Recognition and Retrieval Conference
CY JAN, 2009
CL San Jose, CA
SP IS&T, SPIE Elect Imaging
DE HTML document analysis; Document Object Model (DOM); Reference parsing;
Support Vector Machine (SVM); Conditional Random Field (CRF)
ID EXTRACTION; REPRESENTATION; METADATA
AB The set of references that typically appear toward the end of journal articles is sometimes, though not always, a field in bibliographic (citation) databases. But even if references do not constitute such a field, they can be useful as a preprocessing step in the automated extraction of other bibliographic data from articles, as well as in computer-assisted indexing of articles. Automation in data extraction and indexing to minimize human labor is key to the affordable creation and maintenance of large bibliographic databases. Extracting the components of references, such as author names, article title, journal name, publication date and other entities, is therefore a valuable and sometimes necessary task. This paper describes a two-step process using statistical machine learning algorithms, to first locate the references in HTML medical articles and then to parse them. Reference locating identifies the reference section in an article and then decomposes it into individual references. We formulate this step as a two-class classification problem based on text and geometric features. An evaluation conducted on 500 articles drawn from 100 medical journals achieves near-perfect precision and recall rates for locating references. Reference parsing identifies the components of each reference. For this second step, we implement and compare two algorithms. One relies on sequence statistics and trains a Conditional Random Field. The other focuses on local feature statistics and trains a Support Vector Machine to classify each individual word, followed by a search algorithm that systematically corrects low confidence labels if the label sequence violates a set of predefined rules. The overall performance of these two reference-parsing algorithms is about the same: above 99% accuracy at the word level, and over 97% accuracy at the chunk level.
C1 [Zou, Jie; Le, Daniel; Thoma, George R.] Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, NIH, Bethesda, MD 20894 USA.
RP Zou, J (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, NIH, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM jzou@mail.nlm.nih.gov
FU Intramural NIH HHS [Z99 LM999999]
NR 40
TC 4
Z9 4
U1 0
U2 5
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1433-2833
EI 1433-2825
J9 INT J DOC ANAL RECOG
JI Int. J. Doc. Anal. Recognit.
PD JUN
PY 2010
VL 13
IS 2
SI SI
BP 107
EP 119
DI 10.1007/s10032-009-0105-9
PG 13
WC Computer Science, Artificial Intelligence
SC Computer Science
GA 613UJ
UT WOS:000279007000004
PM 20640222
ER
PT J
AU Burgio, KL
Kraus, SR
Borello-France, D
Chai, TC
Kenton, K
Goode, PS
Xu, Y
Kusek, JW
AF Burgio, Kathryn L.
Kraus, Stephen R.
Borello-France, Diane
Chai, Toby C.
Kenton, Kimberly
Goode, Patricia S.
Xu, Yan
Kusek, John W.
CA Urinary Incontinence Treatment Net
TI The effects of drug and behavior therapy on urgency and voiding
frequency
SO INTERNATIONAL UROGYNECOLOGY JOURNAL
LA English
DT Article
DE Behavioral treatment; Drug therapy; Overactive bladder; Urge
incontinence; Urinary frequency; Urinary urgency
ID URINARY-TRACT FUNCTION; OVERACTIVE BLADDER; OLDER WOMEN; INCONTINENCE;
STANDARDIZATION; TERMINOLOGY; EFFICACY
AB The objective of this study was to examine the effects of drug therapy alone and combined with behavioral therapy on urgency and 24-voiding frequency in women with urge-predominant incontinence and to identify predictors of change.
A planned analysis of data from a multi-site, randomized, controlled trial (N = 307). Bladder diaries were used to document voids, incontinence, and urgency severity.
Urgency scores decreased significantly within both treatment groups, but changes did not differ between groups (p = 0.30). Improvement in urgency was associated with greater baseline urgency (p < 0.0001) and black ethnicity (p = 0.03). Voiding frequency increased with drug alone and decreased slightly with combined therapy (p = 0.009), and improvement was associated with combined treatment (p < 0.0001), higher baseline frequency (p < 0.0001), and lower baseline incontinence episode frequency (p = 0.001).
Although combined drug and behavioral therapy does not appear to improve urgency more than drug alone, it resulted in better outcomes on voiding frequency.
C1 [Burgio, Kathryn L.; Goode, Patricia S.] Dept Vet Affairs, Geriatr Res Educ & Clin Ctr, Birmingham, AL 35233 USA.
[Burgio, Kathryn L.; Goode, Patricia S.] Univ Alabama, Birmingham, AL USA.
[Kraus, Stephen R.] Univ Texas Hlth Sci Ctr, San Antonio, TX USA.
[Borello-France, Diane] Duquesne Univ, Pittsburgh, PA 15219 USA.
[Chai, Toby C.] Univ Maryland, Baltimore, MD 21201 USA.
[Kenton, Kimberly] Loyola Univ, Med Ctr, Maywood, IL 60153 USA.
[Xu, Yan] New England Res Inst, Watertown, MA 02172 USA.
[Kusek, John W.] NIDDKD, NIH, Bethesda, MD 20892 USA.
RP Burgio, KL (reprint author), Dept Vet Affairs, Geriatr Res Educ & Clin Ctr, 11G 700 S 19th St, Birmingham, AL 35233 USA.
EM kburgio@uab.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases [U01 DK
58225, U01 DK58234, U01 DK58229, U01 DK58231, U01 DK60397, U01 DK60401,
U01 DK60395, U01 DK60393, U01 DK60380, U01 DK60379]; Pfizer, Inc.
FX This study was supported by grants from the National Institute of
Diabetes and Digestive and Kidney Diseases (U01 DK 58225, U01 DK58234,
U01 DK58229, U01 DK58231, U01 DK60397, U01 DK60401, U01 DK60395, U01
DK60393, U01 DK60380, U01 DK60379). Pfizer, Inc. provided additional
support, including donation of study drugs and funding.
NR 27
TC 11
Z9 13
U1 1
U2 3
PU SPRINGER LONDON LTD
PI LONDON
PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND
SN 0937-3462
J9 INT UROGYNECOL J
JI Int. Urogynecol. J.
PD JUN
PY 2010
VL 21
IS 6
BP 711
EP 719
DI 10.1007/s00192-010-1100-x
PG 9
WC Obstetrics & Gynecology; Urology & Nephrology
SC Obstetrics & Gynecology; Urology & Nephrology
GA 587CF
UT WOS:000276964000015
PM 20143047
ER
PT J
AU Menotti-Raymond, M
Deckman, KH
David, V
Myrkalo, J
O'Brien, SJ
Narfstrom, K
AF Menotti-Raymond, Marilyn
Deckman, Koren Holland
David, Victor
Myrkalo, Jaimie
O'Brien, Stephen J.
Narfstrom, Kristina
TI Mutation Discovered in a Feline Model of Human Congenital Retinal
Blinding Disease
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID CONE-ROD HOMEOBOX; DOMINANT RETINITIS-PIGMENTOSA; TRANSCRIPTION FACTOR
CRX; MESSENGER-RNA DECAY; GENE-THERAPY; DOMESTIC CAT; MOUSE MODEL;
RADIATION HYBRID; ABYSSINIAN CATS; CANINE MODEL
AB PURPOSE. To elucidate the gene defect in a pedigree of cats segregating for autosomal dominant rod-cone dysplasia (Rdy), a retinopathy characterized extensively from a clinical perspective. Disease expression in Rdy cats is comparable to that in young patients with congenital blindness (Leber congenital amaurosis [LCA] or retinitis pigmentosa [RP]).
METHODS. A pedigree segregating for Rdy was generated and phenotyped by clinical ophthalmic examination methods including ophthalmoscopy and full-field flash electroretinography. Short tandem repeat loci tightly linked to candidate genes for autosomal dominant retinitis pigmentosa in humans were genotyped in the pedigree.
RESULTS. Significant linkage was established to the candidate gene CRX (LOD = 5.56, theta = 0) on cat chromosome E2. A single base pair deletion was identified in exon 4 (n.546delC) in affected individuals but not in unaffected littermates. This mutation generates a frame shift in the transcript, introducing a premature stop codon truncating the putative CRX peptide, which would eliminate the critical transcriptional activation region. Clinical observations corroborate previously reported clinical reports about Rdy. Results show that the cone photoreceptor system was more severely affected than the rods in the early disease process.
CONCLUSIONS. A putative mutation causative of the Rdy phenotype has been described as a single base pair deletion in exon 4 of the CRX gene, thus identifying the first animal model for CRX-linked disease that closely resembles the human disease. As such, it will provide valuable insights into the mechanisms underlying these diseases and their variable presentation, as well as providing a suitable model for testing therapies for these diseases. (Invest Ophthalmol Vis Sci. 2010; 51: 2852-2859) DOI: 10.1167/iovs.09-4261
C1 [Menotti-Raymond, Marilyn; David, Victor; O'Brien, Stephen J.] NCI, Lab Genom Divers, Frederick, MD 21702 USA.
[Deckman, Koren Holland; Myrkalo, Jaimie] Gettysburg Coll, Dept Chem, Gettysburg, PA 17325 USA.
[Narfstrom, Kristina] Univ Missouri, Coll Vet Med, Dept Vet Med & Surg, Columbia, MO 65211 USA.
[Narfstrom, Kristina] Univ Missouri, Mason Eye Inst, Dept Ophthalmol, Columbia, MO USA.
RP Menotti-Raymond, M (reprint author), NCI, Lab Genom Divers, Bldg 560,Room 11-38, Frederick, MD 21702 USA.
EM raymondm@mail.nih.gov
FU University of Iowa Foundation; Research to Prevent Blindness; National
Cancer Institute, National Institutes of Health
FX Supported by the University of Iowa Foundation, an unrestricted grant
from Research to Prevent Blindness, and federal funds from the National
Cancer Institute, National Institutes of Health. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the
U.S. Government.
NR 84
TC 25
Z9 26
U1 0
U2 4
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD JUN
PY 2010
VL 51
IS 6
BP 2852
EP 2859
DI 10.1167/iovs.09-4261
PG 8
WC Ophthalmology
SC Ophthalmology
GA 598OC
UT WOS:000277846500005
PM 20053974
ER
PT J
AU Fang, JZ
Fang, D
Silver, PB
Wen, F
Li, B
Ren, XR
Lin, Q
Caspi, RR
Su, SB
AF Fang, Jiazhu
Fang, Dan
Silver, Phyllis B.
Wen, Feng
Li, Bing
Ren, Xiangrong
Lin, Qing
Caspi, Rachel R.
Su, Shao Bo
TI The Role of TLR2, TRL3, TRL4, and TRL9 Signaling in the Pathogenesis of
Autoimmune Disease in a Retinal Autoimmunity Model
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID TOLL-LIKE RECEPTOR; ENCEPHALITOGENIC T-CELLS;
MYCOBACTERIUM-TUBERCULOSIS; PERTUSSIS TOXIN; DENDRITIC CELLS; CUTTING
EDGE; MYD88-DEFICIENT MICE; INNATE IMMUNITY; ACTIVATION; INFECTION
AB PURPOSE. Induction of tissue-specific experimental autoimmune diseases involves the use of complete Freund adjuvant containing Mycobacterium tuberculosis, whose recognition by the innate immune system depends on Toll-like receptors (TLRs) that signal through the adaptor molecule MyD88. The authors' previous study showed that MyD88(-/-) mice, but not TLR2(-/-), TLR4(-/-), or TLR9(-/-) mice, were resistant to experimental autoimmune uveitis (EAU).
METHODS. The EAU induction in mice deficient in TLR3 or mice double deficient in TLR2+4, TLR2+9, and TLR4+9 was examined and the role of the TLR agonists in the adjuvant effect involved in the induction of EAU was assessed.
RESULTS. TLR3-deficient and TLR2+4, TLR2+9, and TLR4+9 double-deficient mice were as susceptible to EAU as their control littermates. However, in mice immunized with a lowdose EAU regimen, TLR4 agonist lipopolysaccharide (LPS) enhanced EAU scores, delayed-type hypersensitivity responses, and antigen-specific T-cell proliferation. Antigen-specific IL-17 and IFN-gamma production by T lymphocytes was markedly increased in the LPS-treated group. The effects of LPS on EAU were abolished by treatment with an LPS deactivator polymyxin B. Inclusion of agonists for TLR2, TRL3, or TRL9 in immunization also enhanced EAU scores.
CONCLUSIONS. These results suggest that signaling of TLR2, TRL3, TRL4, and TRL9 is highly redundant in the adjuvant effect needed to induce EAU and that diverse microbial infections may contribute to the pathogenesis of diseases such as uveitis. (Invest Ophthalmol Vis Sci. 2010;51:3092-3099) DOI: 10.1167/iovs.09-4754
C1 [Fang, Jiazhu; Fang, Dan; Wen, Feng; Li, Bing; Ren, Xiangrong; Lin, Qing; Su, Shao Bo] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Guangdong, Peoples R China.
[Silver, Phyllis B.; Caspi, Rachel R.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Su, SB (reprint author), Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, 54 S Xianlie Rd, Guangzhou 510060, Guangdong, Peoples R China.
EM shaobo.su@gmail.com
OI Lin, Qing/0000-0002-8890-800X; Caspi, Rachel/0000-0002-7140-7671
FU National Basic Research Program of China [2007CB512206]; National
Natural Science Foundation of China [30772011]; Science and Technology
Planning Project of Guangdong Province of China [2006B36006004]
FX Supported in part by National Basic Research Program of China Grant
2007CB512206, National Natural Science Foundation of China Grant
30772011, and Science and Technology Planning Project of Guangdong
Province of China Grant 2006B36006004.
NR 51
TC 37
Z9 43
U1 0
U2 7
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 JUN
PY 2010
VL 51
IS 6
BP 3092
EP 3099
DI 10.1167/iovs.09-4754
PG 8
WC Ophthalmology
SC Ophthalmology
GA 598OC
UT WOS:000277846500037
PM 20107166
ER
PT J
AU Anne, A
Bagayoko, CO
Fontelo, P
AF Anne, A.
Bagayoko, C. O.
Fontelo, P.
TI The evaluation of French version of BabelMeSH
SO IRBM
LA French
DT Article
DE BabelMeSH; PubMed; French language translation
AB BabelMeSH is a multilingual search tool for Medline/PubMed. It is intended for users whose primary language is not English. The languages currently supported are: Arabic, Chinese, French, German, Italian, Japanese. Korean, Portuguese, Russian, Spanish and Swedish. The goal of this work is to evaluate the usability and effectiveness of the French version. This study consisted of two parts: (I) evaluation of translation of French keywords by BabelMeSH, (2) user feedback. We used two sets of keywords: a list of authors' keywords in medical journals published in French and a list of terms derived from Web server logs submitted by French-speaking users to search BabelMeSH. English translations by the authors were compared with those translated by BabelMeSH. The accuracy of translation of user submitted terms was evaluated. An online questionnaire using the 5-point Likert scale was used to evaluate user opinion on the usefulness of BabelMeSH. One hundred and seventy-four author keywords and 179 user keywords in French were randomly selected to search Medline/PubMed via BabelMeSH. With the author-generated keywords. BabelMeSH exactly matched (word-for-word) the authors' translations for 69 terms; translations were accurate (similar concept) for 69 keywords; multiple suggestions were given for 19. one of which was the same as the authors' translation or considered accurate. Partial matches (compound words) were found for 22 keywords. BabelMeSH translations were incorrect for 21 terms. For user search terms, 135 translations and suggestions were considered accurate, 15 partially accurate, 21 were incorrect. Of the eight with multiple suggestions, only one was accurate. Six responses were received from the online questionnaire. The average ratings (5: agree, I: disagree) for the following statements were: (1) that BabelMeSH was useful: 4.3: (2) the overall quality of citations retrieved was excellent: 4.3; and (3) that they would continue to use BabelMeSH: 4.6. All declared that they had previously searched Medline in English and all, except one, stated that they would recommend it to others. BabelMeSH is an alternative resource for researchers whose native language is other than English. Limited user feedback and the results of an objective evaluation seem to indicate that it could be a useful addition to multilanguage search tools for Medline/PubMed. However, at the time we conducted this study, the development of BabelMeSH was not finished. Therefore, it might be necessary to evaluate BabelMeSH French version in future. (C) 2009 Elsevier Masson SAS. All rights reserved.
C1 [Bagayoko, C. O.] Hop Univ Geneve, Serv Informat Med, CH-1211 Geneva 14, Switzerland.
[Anne, A.; Fontelo, P.] US Natl Lib Med, Bethesda, MD 20894 USA.
[Anne, A.; Bagayoko, C. O.] Univ Bamako, Fac Med Pharm & Odontostomatol, Bamako, Mali.
RP Bagayoko, CO (reprint author), Hop Univ Geneve, Serv Informat Med, 24 Rue Micheli Du Crest, CH-1211 Geneva 14, Switzerland.
EM Cob@hcuge.ch
NR 8
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1959-0318
J9 IRBM
JI IRBM
PD JUN
PY 2010
VL 31
IS 3
BP 170
EP 174
DI 10.1016/j.irbm.2009.06.006
PG 5
WC Engineering, Biomedical
SC Engineering
GA 618AY
UT WOS:000279324700005
ER
PT J
AU Kiwanuka, N
Robb, M
Laeyendecker, O
Kigozi, G
Wabwire-Mangen, F
Makumbi, FE
Nalugoda, F
Kagaayi, J
Eller, M
Eller, LA
Serwadda, D
Sewankambo, NK
Reynolds, SJ
Quinn, TC
Gray, RH
Wawer, MJ
Whalen, CC
AF Kiwanuka, Noah
Robb, Merlin
Laeyendecker, Oliver
Kigozi, Godfrey
Wabwire-Mangen, Fred
Makumbi, Fredrick E.
Nalugoda, Fred
Kagaayi, Joseph
Eller, Michael
Eller, Leigh Anne
Serwadda, David
Sewankambo, Nelson K.
Reynolds, Steven J.
Quinn, Thomas C.
Gray, Ronald H.
Wawer, Maria J.
Whalen, Christopher C.
TI HIV-1 Viral Subtype Differences in the Rate of CD4(+) T-Cell Decline
Among HIV Seroincident Antiretroviral Naive Persons in Rakai District,
Uganda
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE HIV-1 subtypes; rate of CD4(+); cell decline; HIV disease progression
ID DISEASE PROGRESSION; TYPE-1 SUBTYPES; INFECTION; COHORT; TANZANIA; LOAD;
ASSOCIATION; LYMPHOCYTES; POPULATION; SYPHILIS
AB Background: Data on the effect of HIV-1 viral subtype on CD4(+) T-cell decline are limited.
Methods: We assessed the rate of CD4(+) T-cell decline per year among 312 HIV seroincident persons infected with different HIV-1 subtypes. Rates of CD4(+) decline by HIV-1 subtype were determined by linear mixed effects models, using an unstructured convariance structure.
Results: A total of 59.6% had D, 15.7% A, 18.9% recombinant viruses (R), and 5.8% multiple subtypes (M). For all subtypes combined, the overall rate of CD4(+) T-cell decline was -34.5 [95% confidence interval (CI), -47.1, -22.0] cells/mu L per yr, adjusted for age, sex, baseline CD4(+) counts, and viral load. Compared with subtype A, the adjusted rate of CD4 cell loss was -73.7/mu L/yr (95% CI, -113.5, -33.8, P < 0.001) for subtype D, -43.2/mu L/yr ( 95% CI, -90.2, 3.8, P = 0.072) for recombinants, and -63.9/mu L/yr ( 95% CI, -132.3, 4.4, P = 0.067) for infection with multiple HIV subtypes. Square-root transformation of CD4(+) cell counts did not change the results.
Conclusions: Infection with subtype D is associated with significantly faster rates of CD4(+) T-cell loss than subtype A. This may explain the more rapid disease progression for subtype D compared with subtype A.
C1 [Kiwanuka, Noah; Wabwire-Mangen, Fred; Makumbi, Fredrick E.; Whalen, Christopher C.] Makerere Univ, Coll Hlth Sci, Sch Publ Hlth, Dept Epidemiol & Biostat, Kampala, Uganda.
[Kiwanuka, Noah; Kigozi, Godfrey; Makumbi, Fredrick E.; Nalugoda, Fred; Kagaayi, Joseph] Uganda Virus Res Inst, Rakai Hlth Sci Program, Dept Res Studies, Entebbe, Uganda.
[Robb, Merlin; Laeyendecker, Oliver; Reynolds, Steven J.; Quinn, Thomas C.] Henry M Jackson Fdn, Dept HIV Res, Rockville, MD USA.
[Laeyendecker, Oliver; Quinn, Thomas C.] NIAID, NIH, Bethesda, MD 20892 USA.
[Eller, Michael; Eller, Leigh Anne] Johns Hopkins Sch Med, Baltimore, MD USA.
[Serwadda, David] Walter Reed Army Inst Res, Silver Spring, MD USA.
[Sewankambo, Nelson K.; Wawer, Maria J.] Makerere Univ, Coll Hlth Sci, Sch Publ Hlth, Dept Dis Control & Environm Hlth, Kampala, Uganda.
[Gray, Ronald H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Whalen, Christopher C.] Univ Georgia, Sch Publ Hlth, Dept Epidemiol, Dept Populat & Family Hlth Sci, Atlanta, GA USA.
RP Kiwanuka, N (reprint author), Makerere Univ, Coll Hlth Sci, Sch Publ Hlth, Dept Epidemiol & Biostat, POB 7072, Kampala, Uganda.
EM nkiwanuka@rhsp.org
RI Laeyendecker, Oliver/B-9331-2009;
OI Sewankambo, Nelson/0000-0001-9362-053X; Laeyendecker,
Oliver/0000-0002-6429-4760
FU Department of the Army; Department of the Army, United States Army
Medical Research and Material Command; Henry M. Jackson Foundation;
Fogarty Foundation [5D43TW00010, 2 D 43 TW000010-19]; NIH; Case Western
Reserve University, USA; Division of Intramural Research, NIAID, NIH
FX Supported by the Department of the Army, United States Army Medical
Research and Material Command Cooperative Agreement DAMD17-98-2-8007 and
the Henry M. Jackson Foundation, grants 5D43TW00010 and 2 D 43
TW000010-19 from the Fogarty Foundation, NIH, and Fogarty AIDS
International Training and Research Program at Case Western Reserve
University, USA, and supported by the Division of Intramural Research,
NIAID, NIH. The content does not necessarily reflect the position or
policies of the US Government, the Department of Army, MRCM, the Henry
M. Jackson Foundation, or the Fogarty Foundation, NIH.
NR 28
TC 52
Z9 53
U1 2
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUN
PY 2010
VL 54
IS 2
BP 180
EP 184
DI 10.1097/QAI.0b013e3181c98fc0
PG 5
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 601XK
UT WOS:000278100600010
PM 20010433
ER
PT J
AU Caceres, CF
Celentano, DD
Coates, TJ
Hartwell, TD
Kasprzyk, D
Kelly, JA
Kozlov, AP
Pequegnat, W
Rotheram-Borus, MJ
Solomon, S
Woelk, G
Wu, ZY
AF Caceres, Carlos F.
Celentano, David D.
Coates, Thomas J.
Hartwell, Tyler D.
Kasprzyk, Danuta
Kelly, Jeffrey A.
Kozlov, Andrei P.
Pequegnat, Willo
Rotheram-Borus, Mary Jane
Solomon, Suniti
Woelk, Godfrey
Wu, Zunyou
CA NIMH Collaborative HIV STD Preven
TI Results of the NIMH Collaborative HIV/Sexually Transmitted Disease
Prevention Trial of a Community Popular Opinion Leader Intervention
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE group-randomized clinical trial; HIV; behavioral intervention; community
norms; sexually transmitted disease
ID SEXUAL-RISK BEHAVIOR; HIV; MEN
AB Objective: To determine whether community populations in community popular opinion leader intervention venues showed greater reductions in sexual risk practices and lower HIV/sexually transmitted disease (STD) incidence than those in comparison venues.
Methods: A 5-country group-randomized trial, conducted from 2002 to 2007, enrolled cohorts from 20 to 40 venues in each country. Venues, matched within country on sexual risk and other factors, were randomly assigned within matched pairs to the community popular opinion leader intervention or an AIDS education comparison. All participants had access to condoms and were assessed with repeated in-depth sexual behavior interviews, STD/HIV testing and treatment, and HIV/STD risk-reduction counseling. Sexual behavior change and HIV/STD incidence were measured over 2 years.
Results: Both intervention and comparison conditions showed declines of approximately 33% in risk behavior prevalence and had comparable diseases incidence within and across countries.
Conclusions: The community-level intervention did not produce greater behavioral risk and disease incidence reduction than the comparison condition, perhaps due to the intensive prevention services received by all participants during the assessment. Repeated detailed self-review of risk behavior practices coupled with HIV/STD testing, treatment, HIV risk-reduction counseling, and condom access can themselves substantially change behavior and disease acquisition.
C1 [NIMH Collaborative HIV STD Preven] NIMH, Bethesda, MD 20892 USA.
[Caceres, Carlos F.] Cayetano Heredia Univ, Lima, Peru.
[Celentano, David D.] Johns Hopkins Univ, Baltimore, MD USA.
[Coates, Thomas J.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Hartwell, Tyler D.] RTI Int, Durham, NC USA.
[Kasprzyk, Danuta] Battelle Mem Inst, Seattle, WA USA.
[Kelly, Jeffrey A.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Kozlov, Andrei P.] St Petersburg State Univ, Biomed Ctr, St Petersburg, Russia.
[Pequegnat, Willo] NIMH, Rockville, MD 20857 USA.
[Solomon, Suniti] YRG Ctr AIDS Res & Educ, Chennai, Tamil Nadu, India.
[Woelk, Godfrey] Univ Zimbabwe, Sch Med, Harare, Zimbabwe.
[Wu, Zunyou] Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China.
RP Caceres, CF (reprint author), Cayetano Heredia Univ, Lima, Peru.
RI Strader, Lisa/H-3083-2013; Kozlov, Andrei/H-2117-2016; Borodkina,
Olga/M-8251-2013;
OI Kozlov, Andrei/0000-0003-4611-1534; Borodkina, Olga/0000-0002-0936-5757;
Granskaya, Juliana/0000-0001-7657-0948
FU National Institute of Mental Health, National Institutes of Health
[U10MH061499, U10MH061513, U10MH061536, U10MH061537, U10MH061543,
U10MH061544`]
FX Supported by National Institute of Mental Health, National Institutes of
Health, through the Cooperative Agreement mechanism (U10MH061499,
U10MH061513, U10MH061536, U10MH061537, U10MH061543, and U10MH061544).
NR 28
TC 1
Z9 1
U1 2
U2 6
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 JUN
PY 2010
VL 54
IS 2
BP 204
EP 214
DI 10.1097/QAI.0b013e3181d61def
PG 11
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 601XK
UT WOS:000278100600014
ER
PT J
AU Bell, TJ
Oberholtzer, JC
AF Bell, Thomas J.
Oberholtzer, John Carl
TI cAMP-induced Auditory Supporting Cell Proliferation is Mediated by ERK
MAPK Signaling Pathway
SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY
LA English
DT Article
DE auditory hair cells; supporting cells; cAMP; ERK
ID ACTIVATED PROTEIN-KINASE; EAR SENSORY EPITHELIA; GROWTH-FACTOR-ALPHA;
S-PHASE ENTRY; HAIR-CELLS; CYCLIC-AMP; B-RAF; INTRACELLULAR SIGNALS;
BALANCE EPITHELIA; ACOUSTIC TRAUMA
AB Sensorineural hearing deficiencies result from the loss of auditory hair cells. This hearing loss is permanent in humans and mammals because hair cells are not spontaneously replaced. In other animals such as birds, this is not the case. Damage to the avian cochlea evokes proliferation of supporting cells and the generation of functionally competent replacement hair cells. Signal transduction pathways are clinically useful as potential therapeutic targets, so there is significant interest in identifying the key signal transduction pathways that regulate the formation of replacement hair cells. In a previous study from our lab, we showed that forskolin (FSK) treatment induces auditory supporting cell proliferation and formation of replacement hair cells in the absence of sound or aminoglycoside treatment. Here, we show that FSK-induced supporting cell proliferation is mediated by cell-specific accumulation of cyclic adenosine monophosphate (cAMP) in avian supporting cells and the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway. By a combination of immunostaining and pharmacological analyses, we show that FSK treatment increases cAMP levels in avian auditory supporting cells and that several ERK MAP inhibitors effectively block FSK-induced supporting cell proliferation. Next, we demonstrate by Western blotting and immunostaining analyses the expression of several ERK MAPK signaling molecules in the avian auditory epithelium and the cell-specific expression of B-Raf in avian auditory supporting cells. Collectively, these data suggest that FSK-induced supporting cell proliferation in the avian auditory epithelium is mediated by increases of cAMP levels in supporting cells and the cell-specific expression of the ERK MAPK family member B-Raf in supporting cells.
C1 [Bell, Thomas J.; Oberholtzer, John Carl] Univ Penn, Sch Med, Div Neuropathol, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Oberholtzer, John Carl] NCI, Bethesda, MD 20892 USA.
RP Bell, TJ (reprint author), Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA.
EM tjbell@upenn.edu
NR 52
TC 4
Z9 4
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1525-3961
J9 JARO-J ASSOC RES OTO
JI JARO
PD JUN
PY 2010
VL 11
IS 2
BP 173
EP 185
DI 10.1007/s10162-009-0205-8
PG 13
WC Neurosciences; Otorhinolaryngology
SC Neurosciences & Neurology; Otorhinolaryngology
GA 619AF
UT WOS:000279397500003
PM 20107853
ER
PT J
AU Strenziok, M
Krueger, F
Pulaski, SJ
Openshaw, AE
Zamboni, G
van der Meer, E
Grafman, J
AF Strenziok, Maren
Krueger, Frank
Pulaski, Sarah J.
Openshaw, Anne E.
Zamboni, Giovanna
van der Meer, Elke
Grafman, Jordan
TI Lower Lateral Orbitofrontal Cortex Density Associated With More Frequent
Exposure to Television and Movie Violence in Male Adolescents
SO JOURNAL OF ADOLESCENT HEALTH
LA English
DT Article
DE Voxel-based morphometry; Media; Aggression
ID MEDIA VIOLENCE; BRAIN; BEHAVIOR
AB The relationship between cortical grey matter density and media violence exposure in healthy male adolescents was investigated using voxel-based morphometry and the Childrens' Report of Exposure to Violence. Adolescents with more frequent exposure have lower left lateral orbitofrontal cortex density-a possible risk factor for altered socioemotional functioning. (C) 2010 Society for Adolescent Health and Medicine. All rights reserved.
C1 [Grafman, Jordan] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA.
[van der Meer, Elke] Humboldt Univ, Dept Cognit Psychol, Berlin, Germany.
RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, 10 Ctr Dr,Bldg 10,Room 7D43, Bethesda, MD 20892 USA.
EM grafmanj@ninds.nih.gov
RI Zamboni, Giovanna/F-3583-2017;
OI Zamboni, Giovanna/0000-0002-6133-3373; Grafman, Jordan
H./0000-0001-8645-4457
FU National Institutes of Health, National Institute of Neurological
Disorders and Stroke
FX This study was funded by the intramural research program of the National
Institutes of Health, National Institute of Neurological Disorders and
Stroke. We thank Drs. Eric Wassermann, Dimitrios Kapogiannis, Edward
Huey, and Rhoshel Lenroot for performing the neurological and
psychiatric examinations on our subjects and Dr. Michele
Cooley-Strickland, Associate Professor of Mental Health at the Bloomberg
School of Public Health, Johns Hopkins University, for allowing us to
use the CREV.
NR 10
TC 5
Z9 5
U1 0
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1054-139X
J9 J ADOLESCENT HEALTH
JI J. Adolesc. Health
PD JUN
PY 2010
VL 46
IS 6
BP 607
EP 609
DI 10.1016/j.jadohealth.2009.11.196
PG 3
WC Psychology, Developmental; Public, Environmental & Occupational Health;
Pediatrics
SC Psychology; Public, Environmental & Occupational Health; Pediatrics
GA 596OO
UT WOS:000277694800015
PM 20472220
ER
PT J
AU Beydoun, MA
Wang, YF
AF Beydoun, May A.
Wang, Youfa
TI Pathways linking socioeconomic status to obesity through depression and
lifestyle factors among young US adults
SO JOURNAL OF AFFECTIVE DISORDERS
LA English
DT Article
DE Depression; Body mass index; Obesity; Socio-economic status; Diet;
Physical activity
ID BODY-MASS INDEX; NATIONAL-COMORBIDITY-SURVEY; PHYSICAL-ACTIVITY; FOOD
INSECURITY; MOOD DISORDERS; MENTAL-HEALTH; UNITED-STATES;
HYPERCORTISOLEMIC DEPRESSION; PSYCHIATRIC-DISORDERS; MAJOR DEPRESSION
AB Obesity and depression are two diseases of major public health importance. While both correlate with each other, potential pathways involving depression that would link socioeconomic status (SES) to lifestyle factors and obesity have not been systematically examined using nationally representative data. Using rich data on 2217 US young adults aged 20-39 years from the 1999-2004 National Health and Nutrition Surveys (NHANES) and multivariate linear and logistic regression models, we examined associations between major depressive disorder (MDD), dietary intake, physical activity (PA), and measured body mass index (BMI) controlling for socio-demographic factors. Further, structural equation models (SEM) were fit to test pathway explaining SES disparities in BMI through MOD and lifestyle factors. Recent prevalence of MDD was lower among young US men than women (6.4% vs. 9.2%) although their prevalence of obesity was similar (21.2% vs. 22.7%). Among women, MDD was associated with higher BMI and inversely associated with PA, but not among men. MDD was specifically associated with increased risk of morbid obesity (BMI >= 40) among women (OR: 2.88 (1.32, 6.30)). Using SEM, a main pathway linking SES to BMI among women was linking SES -> food insecurity -> MDD -> PA -> BMI. A main pathway linking MDD to BMI in both genders was going through PA rather than overall dietary quality. Gender and ethnic differences existed underlying how MDD. SES and lifestyle factors were associated with adiposity. Future prospective studies are needed to examine potential mechanisms using physiological markers of depression, lifestyle and obesity. Published by Elsevier B.V.
C1 [Beydoun, May A.; Wang, Youfa] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Human Nutr, Dept Int Hlth, Baltimore, MD 21205 USA.
[Beydoun, May A.] NIA, NIH, IRP, Baltimore, MD 21224 USA.
RP Wang, YF (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Human Nutr, Dept Int Hlth, 615 N Wolfe St,E2546, Baltimore, MD 21205 USA.
EM ywang@jhsph.edu
FU National Institutes of Health (NIH); NIDDK; NICHD [R01DK81335-01A1,
1R03HD058077-01A1]; NIH, National Institute on Aging
FX The study was supported in part by research grants from the National
Institutes of Health (NIH, the NIDDK and NICHD, R01DK81335-01A1,
1R03HD058077-01A1), and by the Intramural Research Program of the NIH,
National Institute on Aging.
NR 62
TC 41
Z9 42
U1 3
U2 29
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0327
J9 J AFFECT DISORDERS
JI J. Affect. Disord.
PD JUN
PY 2010
VL 123
IS 1-3
BP 52
EP 63
DI 10.1016/j.jad.2009.09.021
PG 12
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 599EX
UT WOS:000277894900007
PM 19853306
ER
PT J
AU Vinh, DC
Sugui, JA
Hsu, AP
Freeman, AF
Holland, SM
AF Vinh, Donald C.
Sugui, Janyce A.
Hsu, Amy P.
Freeman, Alexandra F.
Holland, Steven M.
TI Invasive fungal disease in autosomal-dominant hyper-IgE syndrome
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Letter
ID INFECTION; STAT3; EPITHELIUM; MUTATIONS
C1 [Vinh, Donald C.; Hsu, Amy P.; Freeman, Alexandra F.; Holland, Steven M.] NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Sugui, Janyce A.] NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Vinh, DC (reprint author), NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM vinhd@niaid.nih.gov
OI VINH, DONALD/0000-0003-1347-7767
FU Canadian Institutes of Health Research; Intramural NIH HHS [Z99
AI999999]
NR 9
TC 39
Z9 40
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD JUN
PY 2010
VL 125
IS 6
BP 1389
EP 1390
DI 10.1016/j.jaci.2010.01.047
PG 2
WC Allergy; Immunology
SC Allergy; Immunology
GA 611PH
UT WOS:000278831000030
PM 20392475
ER
PT J
AU Moss, RB
Davey, RT
Steigbigel, RT
Fang, F
AF Moss, Ronald B.
Davey, Richard T.
Steigbigel, Roy T.
Fang, Fang
TI Targeting pandemic influenza: a primer on influenza antivirals and drug
resistance
SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
LA English
DT Review
DE flu; DAS181; H274Y; oseltamivir; zanamivir; peramivir
ID SIALIDASE FUSION PROTEIN; H1N1 VIRUS-INFECTION; OSELTAMIVIR-RESISTANT;
NEURAMINIDASE INHIBITORS; UNITED-STATES; EMERGENCE; THERAPY; A(H1N1);
HUMANS; METAANALYSIS
AB The emergence of the 2009 H1N1 pandemic influenza A virus, as well as constant antigenic drift of seasonal influenza, underscores the remarkable versatility of this virus in adapting to the human population. While vaccines are the principal public health defence against influenza, rapid vaccine development can be a daunting task. Antiviral drugs offer the promise of inhibiting influenza regardless of its genetic variations. However, the rapid rise of resistance to several antivirals has highlighted the need for developing novel therapeutics with reduced drug resistance potential. In this review, we will summarize the effects of the currently licensed anti-influenza drugs as well as the candidates in development against the seasonal and the 2009 H1N1 pandemic influenza A virus with an emphasis on drug resistance.
C1 [Moss, Ronald B.; Fang, Fang] NexBio Inc, San Diego, CA USA.
[Davey, Richard T.] NIAID, NIH, Bethesda, MD 20892 USA.
[Steigbigel, Roy T.] SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA.
RP Moss, RB (reprint author), NexBio Inc, San Diego, CA USA.
EM rmoss@nexbio.com
NR 62
TC 33
Z9 40
U1 0
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-7453
J9 J ANTIMICROB CHEMOTH
JI J. Antimicrob. Chemother.
PD JUN
PY 2010
VL 65
IS 6
BP 1086
EP 1093
DI 10.1093/jac/dkq100
PG 8
WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy
SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy
GA 597CV
UT WOS:000277734500002
PM 20375034
ER
PT J
AU Black, DO
AF Black, David O.
TI How to Compromise with Your School District Without Compromising Your
Child: A Field Guide for Getting Effective Services for Children with
Special Needs
SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
LA English
DT Book Review
C1 [Black, David O.] NIMH, Pediat & Dev Neurosci Branch, NIH, Bethesda, MD 20892 USA.
RP Black, DO (reprint author), NIMH, Pediat & Dev Neurosci Branch, NIH, 10 Ctr Dr MSC 1255,Bldg 10,Room 4N208, Bethesda, MD 20892 USA.
EM blackdavid@mail.nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0162-3257
J9 J AUTISM DEV DISORD
JI J. Autism Dev. Disord.
PD JUN
PY 2010
VL 40
IS 6
BP 781
EP 781
DI 10.1007/s10803-009-0839-8
PG 1
WC Psychology, Developmental
SC Psychology
GA 592IL
UT WOS:000277372000013
ER
PT J
AU Orban, T
Farkas, K
Jalahej, H
Kis, J
Treszl, A
Falk, B
Reijonen, H
Wolfsdorf, J
Ricker, A
Matthews, JB
Tchao, N
Sayre, P
Bianchine, P
AF Orban, Tihamer
Farkas, Klara
Jalahej, Heyam
Kis, Janos
Treszl, Andras
Falk, Ben
Reijonen, Helena
Wolfsdorf, Joseph
Ricker, Alyne
Matthews, Jeffrey B.
Tchao, Nadio
Sayre, Peter
Bianchine, Pete
TI Autoantigen-specific regulatory T cells induced in patients with type 1
diabetes mellitus by insulin B-chain immunotherapy
SO JOURNAL OF AUTOIMMUNITY
LA English
DT Article
DE Type 1 diabetes mellitus; Insulin B-chain immunotherapy; Clinical trial;
Autoantigen-specific regulatory T cells
ID GLUTAMIC-ACID DECARBOXYLASE; PRIMARY IMMUNE-RESPONSE;
RHEUMATOID-ARTHRITIS; MULTIPLE-SCLEROSIS; DOUBLE-BLIND; NOD MICE;
TGF-BETA; VACCINATION; PEPTIDE; TRIAL
AB There is a growing body of evidence to suggest that the autoimmunity observed in type 1 diabetes mellitus (T1DM) is the result of an imbalance between autoaggressive and regulatory cell subsets. Therapeutics that supplement or enhance the existing regulatory subset are therefore a much sought after goal in this indication. Here, we report the results of a double blind, placebo controlled, phase I clinical trial of a novel antigen-specific therapeutic in 12 subjects with recently diagnosed T1DM. Our primary objective was to test its safety. The study drug, human insulin B-chain in incomplete Freund's adjuvant (IFA) was administered as a single intramuscular injection, with subjects followed for 2 years. All subjects completed therapy and all follow-up visits. The therapy was generally safe and well-tolerated. Mixed meal stimulated C-peptide responses, measured every 6 months, showed no statistical differences between arms. All patients vaccinated with the autoantigen, but none who received placebo, developed robust insulin-specific humoral and T cell responses. Up to two years following the single injection, in peripheral blood from subjects in the experimental arm, but not the control arm, insulin B-chain-specific CD4+ T cells could be isolated and cloned that showed phenotypic and functional characteristics of regulatory T cells. The induction of a lasting, robust immune response generating autoantigen-specific regulatory T cells provides strong justification for further testing of this therapy in type 1 diabetes. (clinicaltrials.gov identifier NCT00057499). (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Orban, Tihamer; Farkas, Klara; Jalahej, Heyam; Kis, Janos; Treszl, Andras; Ricker, Alyne] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Kis, Janos] Polyclin Hosp Bros, Budapest, Hungary.
[Treszl, Andras] Inst Med Biometrie & Epidemiol, Zentrum Expt Med, Hamburg, Germany.
[Falk, Ben; Reijonen, Helena] Benaroya Res Inst Virginia Mason, Seattle, WA USA.
[Wolfsdorf, Joseph] Childrens Hosp Boston, Boston, MA USA.
[Matthews, Jeffrey B.; Tchao, Nadio; Sayre, Peter] UCSF, Immune Tolerance Network, San Francisco, CA USA.
[Bianchine, Pete] NIAID, Bethesda, MD 20892 USA.
RP Orban, T (reprint author), Joslin Diabet Ctr, Room 433,1 Joslin Pl, Boston, MA 02215 USA.
EM torban@joslin.harvard.edu
FU National Institute of Allergy and Infectious Diseases; National
Institute of Diabetes, and Digestive and Kidney Disease [N01-A1-15416];
Juvenile Diabetes Research Foundation
FX This research was performed as a project of the Immune Tolerance
Network, a collaborative clinical research project head-quartered at the
University of California San Francisco and supported by the National
Institute of Allergy and Infectious Diseases, the National Institute of
Diabetes, and Digestive and Kidney Disease "(NIH contract #N01-A1-15416
NIH/NIAID)" and the Juvenile Diabetes Research Foundation.
NR 50
TC 52
Z9 56
U1 0
U2 6
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0896-8411
J9 J AUTOIMMUN
JI J. Autoimmun.
PD JUN
PY 2010
VL 34
IS 4
BP 408
EP 415
DI 10.1016/j.jaut.2009.10.005
PG 8
WC Immunology
SC Immunology
GA 598WF
UT WOS:000277869500009
PM 19931408
ER
PT J
AU Periasamy, S
Kolenbrander, PE
AF Periasamy, Saravanan
Kolenbrander, Paul E.
TI Central Role of the Early Colonizer Veillonella sp in Establishing
Multispecies Biofilm Communities with Initial, Middle, and Late
Colonizers of Enamel
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID FUSOBACTERIUM-NUCLEATUM; SALIVA; COMMUNICATION; MICROFLORA; ADHERENCE;
SURFACES; BACTERIA; FLOW
AB Human dental biofilm communities comprise several species, which can interact cooperatively or competitively. Bacterial interactions influence biofilm formation, metabolic changes, and physiological function of the community. Lactic acid, a common metabolite of oral bacteria, was measured in the flow cell effluent of one-, two- and three-species communities growing on saliva as the sole nutritional source. We investigated singles-pecies and multispecies colonization by using known initial, early, middle, and late colonizers of enamel. Fluorescent-antibody staining and image analysis were used to quantify the biomass in saliva-fed flow cells. Of six species tested, only the initial colonizer Actinomyces oris exhibited significant growth. The initial colonizer Streptococcus oralis produced lactic acid but showed no significant growth. The early colonizer Veillonella sp. utilized lactic acid in two- and three-species biofilm communities. The biovolumes of all two-species biofilms increased when Veillonella sp. was present as one of the partners, indicating that this early colonizer promotes mutualistic community development. All three-species combinations exhibited enhanced growth except one, i.e., A. oris, Veillonella sp., and the middle colonizer Porphyromonas gingivalis, indicating specificity among three-species communities. Further specificity was seen when Fusobacterium nucleatum (a middle colonizer), Aggregatibacter actinomycetemcomitans (a late colonizer), and P. gingivalis did not grow with S. oralis in two-species biofilms, but inclusion of Veillonella sp. resulted in growth of all three-species combinations. We propose that commensal veillonellae use lactic acid for growth in saliva and that they communicate metabolically with initial, early, middle, and late colonizers to establish multispecies communities on enamel.
C1 [Periasamy, Saravanan; Kolenbrander, Paul E.] NIDCR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA.
RP Kolenbrander, PE (reprint author), NIDCR, Oral Infect & Immun Branch, NIH, Bldg 30,Room 310,30 Convent Dr,MSC 4350, Bethesda, MD 20892 USA.
EM pkolenbrander@dir.nidcr.nih.gov
FU National Institute of Dental and Craniofacial Research, National
Institutes of Health; Colgate-Palmolive Co. CRADA
FX This research was supported in part by the Intramural Research Program
of the National Institute of Dental and Craniofacial Research, National
Institutes of Health, and in part by the Colgate-Palmolive Co. CRADA.
NR 21
TC 54
Z9 54
U1 1
U2 10
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0021-9193
J9 J BACTERIOL
JI J. Bacteriol.
PD JUN
PY 2010
VL 192
IS 12
BP 2965
EP 2972
DI 10.1128/JB.01631-09
PG 8
WC Microbiology
SC Microbiology
GA 601XT
UT WOS:000278102000003
PM 20154130
ER
PT J
AU Waters, AM
Henry, J
Mogg, K
Bradley, BP
Pine, DS
AF Waters, Allison M.
Henry, Julie
Mogg, Karin
Bradley, Brendan P.
Pine, Daniel S.
TI Attentional bias towards angry faces in childhood anxiety disorders
SO JOURNAL OF BEHAVIOR THERAPY AND EXPERIMENTAL PSYCHIATRY
LA English
DT Article
DE Attentional bias; Anxiety disorders; Children
ID NONANXIOUS CHILDREN; FACIAL EXPRESSIONS; THREATENING FACES; EMOTIONAL
FACES; ADOLESCENTS; INFORMATION; DEPRESSION; AVOIDANCE; SYMPTOMS; ADULTS
AB Objective: To examine attentional bias towards angry and happy faces in 8-12 year old children with anxiety disorders (n = 29) and non-anxious controls (n = 24).
Method: Children completed a visual-probe task in which pairs of angry/neutral and happy/neutral faces were displayed for 500 ms and were replaced by a visual probe in the spatial location of one of the faces.
Results: Children with more severe anxiety showed an attentional bias towards angry relative to neutral faces, compared with anxious children who had milder anxiety and non-anxious control children, both of whom did not show an attentional bias for angry faces. Unexpectedly, all groups showed an attentional bias towards happy faces relative to neutral ones.
Conclusions: Anxiety symptom severity increases attention to threat stimuli in anxious children. This association may be due to differing threat appraisal processes or emotion regulation strategies. (c) 2010 Elsevier Ltd. All rights reserved.
C1 [Waters, Allison M.; Henry, Julie] Griffith Univ, Sch Psychol, Griffith, Qld 4222, Australia.
[Mogg, Karin; Bradley, Brendan P.] Univ Southampton, Southampton SO9 5NH, Hants, England.
[Pine, Daniel S.] NIMH, Bethesda, MD 20892 USA.
RP Waters, AM (reprint author), Griffith Univ, Sch Psychol, Griffith, Qld 4222, Australia.
EM a.waters@griffith.edu.au
RI Bradley, Brendan/B-9724-2008; Mogg, Karin/C-1181-2008;
OI Mogg, Karin/0000-0002-2738-7378; Bradley, Brendan/0000-0003-2801-4271;
Waters, Allison/0000-0003-2453-793X
NR 38
TC 55
Z9 59
U1 8
U2 23
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0005-7916
J9 J BEHAV THER EXP PSY
JI J. Behav. Ther. Exp. Psychiatry
PD JUN
PY 2010
VL 41
IS 2
BP 158
EP 164
DI 10.1016/j.jbtep.2009.12.001
PG 7
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 565NC
UT WOS:000275299400012
PM 20060097
ER
PT J
AU Clark, DJ
AF Clark, David J.
TI Nucleosome Positioning, Nucleosome Spacing and the Nucleosome Code
SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
LA English
DT Article
ID YEAST CUP1 CHROMATIN; SACCHAROMYCES-CEREVISIAE; MICROCOCCAL NUCLEASE;
HISTONE OCTAMER; HIGH-RESOLUTION; TRANSCRIBING POLYMERASE; PLASMID
CHROMATIN; GLOBIN GENE; IN-VIVO; DNA
AB Nucleosome positioning has been the subject of intense study for many years. The properties of micrococcal nuclease, the enzyme central to these studies, are discussed. The various methods used to determine nucleosome positions in vitro and in vivo are reviewed critically. These include the traditional low resolution method of indirect end-labelling, high resolution methods such as primer extension, monomer extension and nucleosome sequencing, and the high throughput methods for genome-wide analysis (microarray hybridisation and parallel sequencing). It is established that low resolution mapping yields an averaged chromatin structure, whereas high resolution mapping reveals the weighted superposition of all the chromatin states in a cell population. Mapping studies suggest that yeast DNA contains information specifying the positions of nucleosomes and that this code is made use of by the cell. It is proposed that the positioning code facilitates nucleosome spacing by encoding information for multiple alternative overlapping nucleosomal arrays. Such a code might facilitate the shunting of nucleosomes from one array to another by ATP-dependent chromatin remodelling machines.
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
RP Clark, DJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bldg 6A,Rm 2A14,6 Ctr Dr, Bethesda, MD 20892 USA.
EM clarkda@mail.nih.gov
FU NIH (NICHD)
FX I thank Gary Felsenfeld, Jeff Hayes and Rohinton Kamakaka for helpful
comments on the manuscript. This research was supported by the
Intramural Research Program of the NIH (NICHD).
NR 57
TC 28
Z9 28
U1 0
U2 6
PU ADENINE PRESS
PI SCHENECTADY
PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA
SN 0739-1102
J9 J BIOMOL STRUCT DYN
JI J. Biomol. Struct. Dyn.
PD JUN
PY 2010
VL 27
IS 6
BP 781
EP 793
PG 13
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 578EL
UT WOS:000276276200006
PM 20232933
ER
PT J
AU Cui, F
Zhurkin, VB
AF Cui, Feng
Zhurkin, Victor B.
TI Structure-based Analysis of DNA Sequence Patterns Guiding Nucleosome
Positioning in vitro
SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
LA English
DT Article
DE Nucleosome; Nucleosome positioning; DNA bending; DNA sequence patterns;
DNA kinks
ID RNA-POLYMERASE-II; B-DNA; CRYSTAL-STRUCTURE; SACCHAROMYCES-CEREVISIAE;
ANISOTROPIC FLEXIBILITY; ANGSTROM RESOLUTION; CHROMATIN-STRUCTURE; CORE
PARTICLE; T-A; HISTONE
AB Recent studies of genome-wide nucleosomal organization suggest that the DNA sequence is one of the major determinants of nucleosome positioning. Although the search for underlying patterns encoded in nucleosomal DNA has been going on for about 30 years, our knowledge of these patterns still remains limited. Based on our evaluations of DNA deformation energy, we developed new scoring functions to predict nucleosome positioning. There are three principal differences between our approach and earlier studies: (i) we assume that the length of nucleosomal DNA varies from 146 to 147 bp; (ii) we consider the anisotropic flexibility of pyrimidine-purine (YR) dimeric steps in the context of their neighbors (e.g., YYRR versus RYRY); (iii) we postulate that alternating AT-rich and GC-rich motifs reflect sequence-dependent interactions between histone arginines and DNA in the minor groove. Using these functions, we analyzed 20 nucleosome positions mapped in vitro at single nucleotide resolution (including clones 601, 603, 605, the pGUB plasmid, chicken beta-globin and three 5S rDNA genes). We predicted 15 of the 20 positions with 1-bp precision, and two positions with 2-bp precision. The predicted position of the '601' nucleosome (i.e., the optimum of the computed score) deviates from the experimentally determined unique position by no more than I bp an accuracy exceeding that of earlier predictions.
Our analysis reveals a clear heterogeneity of the nucleosomal sequences which can be divided into two groups based on the positioning 'rules' they follow. The sequences of one group are enriched by highly deformable YR/YYRR motifs at the minor-groove bending sites SHL +/- 3.5 and +/- 5.5, which is similar to the a-satellite sequence used in most crystallized nucleosomes. Apparently, the positioning of these nucleosomes is determined by the interactions between histones H2A/H2B and the terminal parts of nucleosomal DNA. In the other group (that includes the '601' clone) the same YR/YYRR motifs occur predominantly at the sites SHL +/- 1.5. The interaction between the H3/H4 tetramer and the central part of the nucleosomal DNA is likely to be responsible for the positioning of nucleosomes of this group, and the DNA trajectory in these nucleosomes may differ in detail from the published structures.
Thus, from the stereochemical perspective, the in vitro nucleosomes studied here follow either an X-ray-like pattern (with strong deformations in the terminal parts of nucleosomal DNA), or an alternative pattern (with the deformations occurring predominantly in the central part of the nucleosomal DNA). The results presented here may be useful for genome-wide classification of nucleosomes, linking together structural and thermodynamic characteristics of nucleosomes with the underlying DNA sequence patterns guiding their position's.
C1 [Cui, Feng; Zhurkin, Victor B.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Zhurkin, VB (reprint author), NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
EM zhurkin@nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX We are grateful to W. Olson, M. Tolstorukov, E. Trifonov and D. Wang for
valuable discussions and to G. Leiman for text editing. This research
was supported by the Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research. This research was
presented in part by the authors at the 16th Conversation (76).
NR 77
TC 38
Z9 41
U1 3
U2 8
PU ADENINE PRESS
PI SCHENECTADY
PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA
SN 0739-1102
J9 J BIOMOL STRUCT DYN
JI J. Biomol. Struct. Dyn.
PD JUN
PY 2010
VL 27
IS 6
BP 821
EP 841
PG 21
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 578EL
UT WOS:000276276200009
PM 20232936
ER
PT J
AU Wang, DF
Ulyanov, NB
Zhurkin, VB
AF Wang, Difei
Ulyanov, Nikolai B.
Zhurkin, Victor B.
TI Sequence-dependent Kink-and-Slide Deformations of Nucleosomal DNA
Facilitated by Histone Arginines Bound in the Minor Groove
SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
LA English
DT Article
DE Nucleosome; Nucleosome positioning; DNA bending; DNA sequence patterns;
DNA kinks
ID MOLECULAR-DYNAMICS SIMULATIONS; B-DNA; CORE PARTICLE; ANGSTROM
RESOLUTION; ANISOTROPIC FLEXIBILITY; DINUCLEOTIDE STEPS;
CRYSTAL-STRUCTURE; HELIX GEOMETRY; NUCLEIC-ACIDS; BINDING
AB In addition to bending and twisting deformabilities, the lateral displacements of the DNA axis (Kink-and-Slide) play an important role in DNA wrapping around the histone core (M. Y. Tolstorukov, A. V. Colasanti, D. M. McCandlish, W. K. Olson, V. B. Zhurkin, J. Mol. Biol. 37/, 725-738 (2007)). Here, we show that these Kink-and-Slide deformations are likely to be stabilized by the arginine residues of histones interacting with the minor groove of DNA. The arginines are positioned asymmetrically in the minor groove, being closer to one strand. The asymmetric arginine-DNA interactions facilitate lateral displacement of base pairs across the DNA grooves, thus leading to a stepwise accumulation of the superhelical pitch of nucleosomal DNA.
To understand the sequence dependence of such Kink-and-Slide deformations, we performed all-atom calculations of DNA hexamers with the YR and RY steps in the center. We found that when the unrestrained DNA deformations are allowed, the YR steps tend to bend into the major groove, and RY steps bend into the minor groove. However, when the nucleosomal Kink-and-Slide deformation is considered, the YR steps prove to be more favorable for bending into the minor groove. Overall, the Kink-and-Slide deformation energy of DNA increases in the order TA < CA < CG < GC < AC < AT. We propose a simple stereochemical model accounting for this sequence dependence. Our results agree with experimental data indicating that the TA step most frequently occurs in the minor-groove kink positions in the most stable nucleosomes.
Our computations demonstrate that the Kink-and-Slide distortion is accompanied by the BI to BII transition. This fact, together with irregularities in the two-dimensional (Roll, Slide) energy contour maps, suggest that the Kink-and-Slide deformations represent a non-harmonic behavior of the duplex. This explains the difference between the two estimates of the DNA deformation energy in nucleosome the earlier one made using knowledge-based elastic energy functions, and the current one based on all-atom calculations.
Our findings are useful for refining the score functions for the prediction of nucleosome positioning. In addition, the reverse bending behavior of the YR and RY steps revealed under the Kink-and-Slide constraint is important for understanding the molecular mechanisms of binding transcription factors (such as p53) to DNA exposed on the surface of nucleosome.
C1 [Wang, Difei; Zhurkin, Victor B.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Ulyanov, Nikolai B.] UCSF, Dept Pharmaceut Chem, San Francisco, CA 94158 USA.
RP Zhurkin, VB (reprint author), NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
EM zhurkin@nih.gov
RI Wang, Difei/E-7066-2010; Ulyanov, Nikolai/G-6998-2014
FU NIH, National Cancer Institute, Center for Cancer Research
FX The authors are grateful to Wilma Olson and Michael Tolstorukov for
valuable discussions and to George Leiman for text editing. This
research was supported, in part, by the Intramural Research Program of
the NIH, National Cancer Institute, Center for Cancer Research. N.B.U.
is indebted to T.L. James for his continuing support.
NR 54
TC 28
Z9 30
U1 2
U2 9
PU ADENINE PRESS
PI SCHENECTADY
PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA
SN 0739-1102
J9 J BIOMOL STRUCT DYN
JI J. Biomol. Struct. Dyn.
PD JUN
PY 2010
VL 27
IS 6
BP 843
EP 859
PG 17
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 578EL
UT WOS:000276276200010
PM 20232937
ER
PT J
AU Ousley, AL
Swarz, JA
Milliken, EL
Ellis, S
AF Ousley, Anita L.
Swarz, Jeffrey A.
Milliken, Erin L.
Ellis, Steven
TI Cancer Education and Effective Dissemination: Information Access is not
Enough
SO JOURNAL OF CANCER EDUCATION
LA English
DT Article
DE Professional education; Information dissemination; Translating research
to practice; Practitioner survey; Provider survey
ID CONTINUING MEDICAL-EDUCATION; SYSTEMATIC REVIEWS; PRIMARY-CARE;
INTERVENTIONS; BEHAVIOR
AB Education is the main avenue for disseminating new research findings into clinical practice. Understanding factors that affect translation of research into practice may help cancer educators design programs that facilitate the time it takes for research-indicated practices to become standard care. To understand various factors, the National Cancer Institute (NCI) Office of Education and Special Initiatives (OESI)(1) with individual cooperation from Oncology Nursing Society (ONS), American Society of Clinical Oncology (ASCO), and Association of Oncology Social Work (AOSW) administered a Practitioner Information Needs survey to five different types of practitioners involved in cancer care. While most of the 2,864 practitioners (83%) agreed they had access to current practice information, practitioners in large practice settings were more likely to report having access to research than those small practice settings. However, only 33% indicated that they had adequate time to access the information. Colleagues or experts within the organization were cited as the most frequently relied on information resource (60%), and peer-reviewed journals were cited as second (57%). Overall, 66% strongly or somewhat agreed that their organizations exhibit effective change management practices. A majority (69%) agreed that implementation of new practices is hindered by the lack of available staff time. Financial factors and the characteristics of the information presented were also believed to be factors contributing to research implementation. Group differences were observed among practitioner groups and practice settings for some factors.
C1 [Ousley, Anita L.] NCI, Off Commun & Educ, NIH, DHHS, Bethesda, MD 20892 USA.
[Ousley, Anita L.] NCI, Off Educ & Special Initiat, Bethesda, MD 20892 USA.
[Milliken, Erin L.] NOVA Res Co, Bethesda, MD USA.
[Ellis, Steven] Univ Massachusetts, Donahue Inst, Hadley, MA USA.
RP Ousley, AL (reprint author), NCI, Off Commun & Educ, NIH, DHHS, 6116 Execut Blvd,Suite 410, Bethesda, MD 20892 USA.
EM ousleya@mail.nih.gov
NR 20
TC 5
Z9 5
U1 1
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0885-8195
EI 1543-0154
J9 J CANCER EDUC
JI J. Cancer Educ.
PD JUN
PY 2010
VL 25
IS 2
BP 196
EP 205
DI 10.1007/s13187-010-0129-3
PG 10
WC Oncology; Education, Scientific Disciplines; Public, Environmental &
Occupational Health
SC Oncology; Education & Educational Research; Public, Environmental &
Occupational Health
GA 603AJ
UT WOS:000278180000015
PM 20440666
ER
PT J
AU Moghaddam, AN
Saber, NR
Wen, H
Finn, JP
Ennis, DB
Gharib, M
AF Moghaddam, Abbas Nasiraei
Saber, Nikoo R.
Wen, Han
Finn, J. Paul
Ennis, Daniel B.
Gharib, Morteza
TI Analytical method to measure three-dimensional strain patterns in the
left ventricle from single slice displacement data
SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE
LA English
DT Article
ID MYOCARDIAL TISSUE TRACKING; STIMULATED ECHOES DENSE; MAGNETIC-RESONANCE;
HARMONIC-PHASE; MOTION TRACKING; ENCODED MRI; HUMAN-HEART;
QUANTIFICATION; CONTRACTION; INFARCTION
AB Background: Displacement encoded Cardiovascular MR (CMR) can provide high spatial resolution measurements of three-dimensional (3D) Lagrangian displacement. Spatial gradients of the Lagrangian displacement field are used to measure regional myocardial strain. In general, adjacent parallel slices are needed in order to calculate the spatial gradient in the through-slice direction. This necessitates the acquisition of additional data and prolongs the scan time. The goal of this study is to define an analytic solution that supports the reconstruction of the out-of-plane components of the Lagrangian strain tensor in addition to the in-plane components from a single-slice displacement CMR dataset with high spatio-temporal resolution. The technique assumes incompressibility of the myocardium as a physical constraint.
Results: The feasibility of the method is demonstrated in a healthy human subject and the results are compared to those of other studies. The proposed method was validated with simulated data and strain estimates from experimentally measured DENSE data, which were compared to the strain calculation from a conventional two-slice acquisition.
Conclusion: This analytical method reduces the need to acquire data from adjacent slices when calculating regional Lagrangian strains and can effectively reduce the long scan time by a factor of two.
C1 [Moghaddam, Abbas Nasiraei; Finn, J. Paul; Ennis, Daniel B.] Univ Calif Los Angeles, Dept Radiol Sci, Diagnost Cardiovasc Imaging Sect, David Geffen Sch Med, Los Angeles, CA 90024 USA.
[Moghaddam, Abbas Nasiraei; Saber, Nikoo R.; Gharib, Morteza] CALTECH, Pasadena, CA 91125 USA.
[Wen, Han] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Moghaddam, AN (reprint author), Univ Calif Los Angeles, Dept Radiol Sci, Diagnost Cardiovasc Imaging Sect, David Geffen Sch Med, Los Angeles, CA 90024 USA.
EM abbas@caltech.edu
RI Wen, Han/G-3081-2010
OI Wen, Han/0000-0001-6844-2997
FU NIH [R00 HL087614]
FX The authors acknowledge the assistance of Dr Juan Alvergue and Dr
Alexander Sassani for helping with clinical part of the study. The
authors acknowledge funding support from NIH R00 HL087614 to DBE.
NR 35
TC 2
Z9 2
U1 0
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1097-6647
J9 J CARDIOVASC MAGN R
JI J. Cardiov. Magn. Reson.
PD JUN 1
PY 2010
VL 12
AR 33
DI 10.1186/1532-429X-12-33
PG 18
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 628CQ
UT WOS:000280092400001
ER
PT J
AU Covian-Nares, JF
Koushik, SV
Puhl, HL
Vogel, SS
AF Covian-Nares, J. Fernando
Koushik, Srinagesh V.
Puhl, Henry L., III
Vogel, Steven S.
TI Membrane wounding triggers ATP release and dysferlin-mediated
intercellular calcium signaling
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE Dysferlin; ATP; Wounding; Repair; Morpholino oligonucleotides
ID DEFICIENT MUSCULAR-DYSTROPHY; MIYOSHI MYOPATHY; SKELETAL-MUSCLE;
EXOCYTOSIS; REPAIR; GENE; ENDOCYTOSIS; OTOFERLIN; PROTEIN; FUSION
AB Dysferlin is a Ca(2+)-binding protein found in many different cell types. It is required for membrane wound repair in muscle, but it is not known whether it has the same function in other cells. Here we report the activation of an intercellular signaling pathway in sea urchin embryos by membrane wounding that evokes Ca(2+) spikes in neighboring cells. This pathway was mimicked by ATP application, and inhibited by apyrase, cadmium, and omega-agatoxin-IVA. Microinjection of dysferlin antisense phosphorodiamidate morpholino oligonucleotides blocked this pathway, whereas control morpholinos did not. Co-injection of mRNA encoding human dysferlin with the inhibitory morpholino rescued signaling activity. We conclude that in sea urchin embryos dysferlin mediates Ca(2+)-triggered intercellular signaling in response to membrane wounding.
C1 [Covian-Nares, J. Fernando; Koushik, Srinagesh V.; Puhl, Henry L., III; Vogel, Steven S.] NIAAA, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA.
RP Vogel, SS (reprint author), NIAAA, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA.
EM stevevog@mail.nih.gov
RI Vogel, Steven/A-3585-2012;
OI Puhl, Henry/0000-0003-3095-7201; Vogel, Steven/0000-0002-3005-2667
FU National Institutes of Health, National Institute on Alcohol Abuse and
Alcoholism, Bethesda [MD 20892]
FX This work was supported by the intramural program of the National
Institutes of Health, National Institute on Alcohol Abuse and
Alcoholism, Bethesda, MD 20892, and by a generous gift from the Jain
Foundation. Deposited in PMC for release after 12 months.
NR 33
TC 31
Z9 31
U1 1
U2 6
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
J9 J CELL SCI
JI J. Cell Sci.
PD JUN 1
PY 2010
VL 123
IS 11
BP 1884
EP 1893
DI 10.1242/jcs.066084
PG 10
WC Cell Biology
SC Cell Biology
GA 598TR
UT WOS:000277862000007
PM 20442251
ER
PT J
AU Batra, A
Latour, LL
Ruetzler, CA
Hallenbeck, JM
Spatz, M
Warach, S
Henning, EC
AF Batra, Ayush
Latour, Lawrence L.
Ruetzler, Christl A.
Hallenbeck, John M.
Spatz, Maria
Warach, Steven
Henning, Erica C.
TI Increased plasma and tissue MMP levels are associated with BCSFB and BBB
disruption evident on post-contrast FLAIR after experimental stroke
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Article
DE blood-brain barrier; blood-CSF barrier; FLAIR; MMPs; MRI; stroke
ID FOCAL CEREBRAL-ISCHEMIA; BRAIN-BARRIER DISRUPTION;
MATRIX-METALLOPROTEINASE EXPRESSION; HEMORRHAGIC TRANSFORMATION; ARTERY
OCCLUSION; CHOROID-PLEXUS; CARDIOEMBOLIC STROKE; REPERFUSION INJURY;
RAT-BRAIN; RECOVERY
AB In this study, we examined the relationship between tissue and blood levels of matrix metalloproteinase (MMP)-2 and MMP-9 through gelatin zymography at multiple time points after experimental stroke. We additionally investigated the association between these levels and the evidence of blood-cerebrospinal fluid (CSF) barrier (BCSFB) and blood-brain barrier (BBB) disruption on post-contrast fluid-attenuated inversion-recovery (FLAIR) imaging. Increased plasma MMP-9 was associated with BCSFB disruption at 1h post-reperfusion. Ventricular enhancement ipsilateral to the stroke was 500 +/- 100%, significantly higher than sham, 24, and 48 h groups. Increased tissue MMP-2 and MMP-9 were associated with BBB disruption at 48 h post-reperfusion. Parenchymal enhancement was 60 +/- 20% for a volume equivalent to 260 +/- 80mm(3). Although the percent enhancement was comparable across groups, the volume of enhancing lesion was significantly higher at 48 h (260 +/- 80mm(3), 100%) in comparison to 1 h (8 +/- 3mm(3), 3%) and 24 h (51mm(3), 18%). These findings support the use of imaging markers of BCSFB and BBB status as indirect measures of MMP regulation in the blood and brain tissue. The methods presented herein should be useful in understanding the link between MMPs, barrier integrity, and subsequent hemorrhagic transformation. Journal of Cerebral Blood Flow & Metabolism (2010) 30, 1188-1199; doi: 10.1038/jcbfm.2010.1; published online 3 March 2010
C1 [Henning, Erica C.] NINDS, Sect Stroke Diagnost & Therapeut, Stroke Branch, NIH, Bethesda, MD 20892 USA.
[Ruetzler, Christl A.; Hallenbeck, John M.] NINDS, Clin Invest Sect, NIH, Bethesda, MD 20892 USA.
[Batra, Ayush] Howard Hughes Med Inst, Natl Inst Hlth Res Scholars Program, Bethesda, MD 20817 USA.
[Batra, Ayush] Case Western Reserve Univ, Cleveland Clin Lerner Coll Med, Cleveland, OH 44106 USA.
RP Henning, EC (reprint author), NINDS, Sect Stroke Diagnost & Therapeut, Stroke Branch, NIH, Bldg 10,Room B1D733,10 Ctr Dr,MSC 1063, Bethesda, MD 20892 USA.
EM henninge@ninds.nih.gov
RI Henning, Erica/E-8542-2010
FU Division of Intramural Research of the National Institute of
Neurological Disorders and Stroke, National Institutes of Health
FX This research was supported by the Division of Intramural Research of
the National Institute of Neurological Disorders and Stroke, National
Institutes of Health. We acknowledge the technical assistance of Paola
Castri, PhD, Yang-Ja Lee-Wickner, PhD, and Christina Stuelten, PhD.
NR 44
TC 19
Z9 24
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD JUN
PY 2010
VL 30
IS 6
BP 1188
EP 1199
DI 10.1038/jcbfm.2010.1
PG 12
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 604GH
UT WOS:000278267000012
PM 20197780
ER
PT J
AU Winer, KK
Sinaii, N
Reynolds, J
Peterson, D
Dowdy, K
Cutler, GB
AF Winer, Karen K.
Sinaii, Ninet
Reynolds, James
Peterson, Donna
Dowdy, Karen
Cutler, Gordon B., Jr.
TI Long-Term Treatment of 12 Children with Chronic Hypoparathyroidism: A
Randomized Trial Comparing Synthetic Human Parathyroid Hormone 1-34
versus Calcitriol and Calcium
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID BONE-MINERAL DENSITY; PARATHYROID-HORMONE-1-34
AB Context: Hypoparathyroidism is among the few hormonal insufficiency states not treated with replacement of the missing hormone. This is the first randomized controlled study in children comparing treatment with synthetic human PTH 1-34 and calcitriol.
Objective: The primary objective was to assess the efficacy and safety of long-term PTH 1-34 vs. calcitriol treatment in the maintenance of normal serum calcium values and renal calcium excretion in children with hypoparathyroidism.
Setting: The study was conducted at a clinical research center.
Subjects: Subjects included 12 children aged 5-14 yr with chronic hypoparathyroidism and without severe renal or hepatic insufficiency.
Study Design: The study was a 3-yr randomized parallel trial comparing twice-daily calcitriol (plus calcium and cholecalciferol in four daily doses) vs. sc PTH 1-34 treatment, with weekly or biweekly monitoring of serum and urine calcium.
Results: Mean predose serum calcium levels were maintained at, or just below, the normal range, and urine calcium levels remained in the normal range throughout the 3-yr study, with no significant differences between treatment groups. Creatinine clearance, corrected for body surface area, did not differ between groups and remained normal throughout the study. Markers of bone turnover were mildly elevated during PTH 1-34 therapy and remained within the normal range during calcitriol therapy. Mean bone mineral density Z-scores at the anterior-posterior lumbar spine, femoral neck, distal radius, and whole body remained within the normal range and did not differ between groups throughout the study. Similarly, height and weight percentiles did not differ between treatment groups and remained normal throughout the 3-yr follow-up.
Conclusion: We conclude that PTH 1-34 therapy is safe and effective in maintaining stable calcium homeostasis in children with hypoparathyroidism. Additionally, PTH 1-34 treatment allowed normal skeletal development because there were no differences in bone mineral accrual, linear growth, or weight gain between the two treatment arms over the 3-yr study period. (J Clin Endocrinol Metab 95: 2680-2688, 2010)
C1 [Winer, Karen K.; Sinaii, Ninet; Reynolds, James; Peterson, Donna; Dowdy, Karen; Cutler, Gordon B., Jr.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
RP Winer, KK (reprint author), NICHHD, ENGB, NIH, Bldg 6100,Room 4B11A, Bethesda, MD 20892 USA.
EM winer@mail.nih.gov
FU National Institute of Child Health and Human Development
FX This work was supported by the Intramural Research Program of the
National Institute of Child Health and Human Development.
NR 15
TC 54
Z9 56
U1 1
U2 4
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD JUN
PY 2010
VL 95
IS 6
BP 2680
EP 2688
DI 10.1210/jc.2009-2464
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 606RD
UT WOS:000278444000022
PM 20392870
ER
PT J
AU Krasnoff, JB
Basaria, S
Pencina, MJ
Jasuja, GK
Vasan, RS
Ulloor, J
Zhang, AQ
Coviello, A
Kelly-Hayes, M
D'Agostino, RB
Wolf, PA
Bhasin, S
Murabito, JM
AF Krasnoff, Joanne B.
Basaria, Shehzad
Pencina, Michael J.
Jasuja, Guneet K.
Vasan, Ramachandran S.
Ulloor, Jagadish
Zhang, Anqi
Coviello, Andrea
Kelly-Hayes, Margaret
D'Agostino, Ralph B.
Wolf, Philip A.
Bhasin, Shalender
Murabito, Joanne M.
TI Free Testosterone Levels Are Associated with Mobility Limitation and
Physical Performance in Community-Dwelling Men: The Framingham Offspring
Study
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID SELF-REPORTED DISABILITY; LOWER-EXTREMITY FUNCTION; HEALTHY OLDER MEN;
MIDDLE-AGED MEN; MUSCLE STRENGTH; BODY-COMPOSITION; ELDERLY-MEN;
ENDOGENOUS TESTOSTERONE; SERUM TESTOSTERONE; SKELETAL-MUSCLE
AB Context: Mobility limitation is associated with increased morbidity and mortality. The relationship between circulating testosterone and mobility limitation and physical performance is incompletely understood.
Objective: Our objective was to examine cross-sectional and prospective relations between baseline sex hormones and mobility limitations and physical performance in community-dwelling older men.
Design, Setting, and Participants: We conducted cross-sectional and longitudinal analyses of 1445 men (mean age 61.0 +/- 9.5 yr) who attended Framingham Offspring Study examinations 7 and 8 (mean 6.6 yr apart). Total testosterone (TT) was measured by liquid chromatography tandem mass spectrometry at examination 7. Cross-sectional and longitudinal analyses of mobility limitation and physical performance were performed with continuous (per SD) and dichotomized [low TT and free testosterone (FT) and high SHBG vs. normal] hormone levels.
Main Outcome Measures: Self-reported mobility limitation, subjective health, usual walking speed, and grip strength were assessed at examinations 7 and 8. Short physical performance battery was performed at examination 7.
Results: Higher continuous FT was positively associated with short physical performance battery score (beta = 0.13; P = 0.008), usual walking speed (beta = 0.02; P = 0.048), and lower risk of poor subjective health [odds ratio (OR) = 0.72; P = 0.01]. In prospective analysis, 1 SD increase in baseline FT was associated with lower risk of developing mobility limitation (OR = 0.78; 95% confidence interval = 0.62-0.97) and progression of mobility limitation (OR = 0.75; 95% confidence interval = 0.60-0.93). Men with low baseline FT had 57% higher odds of reporting incident mobility limitation (P = 0.03) and 68% higher odds of worsening of mobility limitation (P = 0.007).
Conclusions: Lower levels of baseline FT are associated with a greater risk of incident or worsening mobility limitation in community-dwelling older men. Whether this risk can be reduced with testosterone therapy needs to be determined by randomized trials. (J Clin Endocrinol Metab 95: 2790-2799, 2010)
C1 [Krasnoff, Joanne B.; Basaria, Shehzad; Ulloor, Jagadish; Zhang, Anqi; Coviello, Andrea; Bhasin, Shalender] Boston Univ, Sch Med, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Sect Preventat Med & Epidemiol, Boston, MA 02118 USA.
[Kelly-Hayes, Margaret; Wolf, Philip A.] Boston Univ, Dept Neurol, Boston, MA 02118 USA.
[Pencina, Michael J.] Boston Univ, Dept Biostat, Boston, MA 02118 USA.
[Pencina, Michael J.; Jasuja, Guneet K.; D'Agostino, Ralph B.] Boston Univ, Dept Math, Stat & Consulting Unit, Boston, MA 02215 USA.
[Pencina, Michael J.; Jasuja, Guneet K.; Vasan, Ramachandran S.; Kelly-Hayes, Margaret; D'Agostino, Ralph B.; Wolf, Philip A.; Murabito, Joanne M.] NHLBI, Framingham Heart Study, Framingham, MA 01701 USA.
[Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Framingham, MA 01701 USA.
RP Bhasin, S (reprint author), Boston Univ, Sch Med, Sect Endocrinol Diabet & Nutr, 670 Albany St,2nd Floor, Boston, MA 02118 USA.
EM Bhasin@bu.edu
RI Perez , Claudio Alejandro/F-8310-2010;
OI Perez , Claudio Alejandro/0000-0001-9688-184X; Murabito,
Joanne/0000-0002-0192-7516; Ramachandran, Vasan/0000-0001-7357-5970
FU National Institute on Aging [1RO1AG31206]; Boston Claude D. Pepper Older
Americans Independence Center [5P30 AG31679]; NIH [AG029451-01A2, 2R01
AG16495]; National Heart, Lung, and Blood Institute [N01-HC-25195];
Centers for Disease Control Foundation
FX This work was supported by National Institute on Aging, 1RO1AG31206;
Boston Claude D. Pepper Older Americans Independence Center, 5P30
AG31679; and NIH grants AG029451-01A2 and 2R01 AG16495. The Framingham
Heart Study of the National Heart, Lung, and Blood Institute of the
National Institutes of Health and Boston University School of Medicine
was supported by the National Heart, Lung, and Blood Institute's
Framingham Heart Study contract No. N01-HC-25195.; Disclosure Summary:
S. B. received research support from the Centers for Disease Control
Foundation.
NR 57
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Z9 60
U1 1
U2 2
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD JUN
PY 2010
VL 95
IS 6
BP 2790
EP 2799
DI 10.1210/jc.2009-2680
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 606RD
UT WOS:000278444000033
PM 20382680
ER
PT J
AU Cheng, K
Ho, K
Stokes, R
Scott, C
Lau, SM
Hawthorne, WJ
O'Connell, PJ
Loudovaris, T
Kay, TW
Kulkarni, RN
Okada, T
Wang, XHL
Yim, SH
Shah, Y
Grey, ST
Biankin, AV
Kench, JG
Laybutt, DR
Gonzalez, FJ
Kahn, CR
Gunton, JE
AF Cheng, Kim
Ho, Kenneth
Stokes, Rebecca
Scott, Christopher
Lau, Sue Mei
Hawthorne, Wayne J.
O'Connell, Philip J.
Loudovaris, Thomas
Kay, Thomas W.
Kulkarni, Rohit N.
Okada, Terumasa
Wang, Xiaohui L.
Yim, Sun Hee
Shah, Yatrik
Grey, Shane T.
Biankin, Andrew V.
Kench, James G.
Laybutt, D. Ross
Gonzalez, Frank J.
Kahn, C. Ronald
Gunton, Jenny E.
TI Hypoxia-inducible factor-1 alpha regulates beta cell function in mouse
and human islets
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; HIPPEL-LINDAU-DISEASE; INSULIN-RESISTANCE
SYNDROME; CORONARY-HEART-DISEASE; FACTOR 1-ALPHA; PANCREATIC-ISLETS;
SERUM FERRITIN; IRON STORES; PROLYL HYDROXYLATION; EMBRYONIC LETHALITY
AB Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is a transcription factor that regulates cellular stress responses. While the levels of HIF-1 alpha protein are tightly regulated, recent studies suggest that it can be active under normoxic conditions. We hypothesized that HIF-1 alpha is required for normal beta cell function and reserve and that dysregulation may contribute to the pathogenesis of type 2 diabetes (T2D). Here we show that HIF-1 alpha protein is present at low levels in mouse and human normoxic beta cells and islets. Decreased levels of HIF-1 alpha impaired glucose-stimulated ATP generation and beta cell function. C57BL/6 mice with beta cell-specific Hif1a disruption (referred to herein as beta-Hif1a-null mice) exhibited glucose intolerance, beta cell dysfunction, and developed severe glucose intolerance on a high-fat diet. Increasing HIP-1 alpha levels by inhibiting its degradation through iron chelation markedly improved insulin secretion and glucose tolerance in control mice fed a high-fat diet but not in beta-Hif1a-null mice. Increasing HIF-1 alpha levels markedly increased expression of ARNT and other genes in human T2D islets and improved their function. Further analysis indicated that HIF-1 alpha was bound to the Arnt promoter in a mouse beta cell line, suggesting direct regulation. Taken together, these findings suggest an important role for HIF-1 alpha in beta cell reserve and regulation of ARNT expression and demonstrate that HIF-1 alpha is a potential therapeutic target for the beta cell dysfunction of T2D.
C1 [Cheng, Kim; Ho, Kenneth; Stokes, Rebecca; Scott, Christopher; Lau, Sue Mei; Gunton, Jenny E.] Garvan Inst Med Res, Diabet & Transcript Factors Grp, Sydney, NSW 2010, Australia.
[Hawthorne, Wayne J.; O'Connell, Philip J.] Univ Sydney, Ctr Transplantat & Renal Res, Westmead Res Inst, Westmead Hosp, Sydney, NSW 2006, Australia.
[Loudovaris, Thomas; Kay, Thomas W.] St Vincents Inst, Melbourne, Vic, Australia.
[Kulkarni, Rohit N.; Okada, Terumasa; Wang, Xiaohui L.; Kahn, C. Ronald] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Kulkarni, Rohit N.; Okada, Terumasa; Wang, Xiaohui L.; Kahn, C. Ronald] Harvard Univ, Sch Med, Boston, MA USA.
[Yim, Sun Hee; Shah, Yatrik; Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA.
[Shah, Yatrik] Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA.
[Grey, Shane T.] GIMR, Gene Therapy & Autoimmun Grp, Sydney, NSW, Australia.
[Biankin, Andrew V.; Kench, James G.] GIMR, Canc Res Program, Sydney, NSW, Australia.
[Biankin, Andrew V.] Bankstown Hosp, Dept Surg, Sydney, NSW, Australia.
[Laybutt, D. Ross] GIMR, Diabet & Obes Res Program, Sydney, NSW, Australia.
[Gunton, Jenny E.] Univ Sydney, Fac Med, Sydney, NSW 2006, Australia.
[Gunton, Jenny E.] Univ New S Wales, St Vincents Clin Sch, Sydney, NSW, Australia.
[Gunton, Jenny E.] Westmead Hosp, Dept Endocrinol & Diabet, Sydney, NSW, Australia.
RP Gunton, JE (reprint author), Garvan Inst Med Res, Diabet & Transcript Factors Grp, 384 Victoria St, Sydney, NSW 2010, Australia.
EM j.gunton@garvan.org.au
RI Grey, Shane/B-3020-2008; Ho, Ken/E-5832-2011;
OI Grey, Shane/0000-0003-2160-1625; Biankin, Andrew/0000-0002-0362-5597
FU National Health and Medical Research Council of Australia (NHMRC);
Diabetes Australia Research Trust; Juvenile Diabetes Research Foundation
(JDRF); Royal Australasian College of Physicians Pfizer and Servier;
L'Oreal Australian For Women in Science; NIH [RO1 DK33201, DK60837-02,
K08, DK02885, RO1 DK67536]; Cancer Institute New South Wales
FX J.E. Gunton was funded by the National Health and Medical Research
Council of Australia (NHMRC), Diabetes Australia Research Trust,
Juvenile Diabetes Research Foundation (JDRF), the Royal Australasian
College of Physicians Pfizer and Servier postdoctoral fellowships, and
the L'Oreal Australian For Women in Science fellowship. W.J. Hawthorne,
P.J. O'Connell, T. Loudovaris, and T.W. Kay were funded by JDRF and
NHMRC. C.R. Kahn was supported by the Mary K. Iacocca Professorship and
NIH grants RO1 DK33201 and DK60837-02. RN. Kulkarni was supported by NIH
grants K08, DK02885, and RO1 DK67536. A.V. Biankin is supported by a
Cancer Institute New South Wales fellowship. A.V. Biankin and J.G. Kench
are supported by an NHMRC program grant. We would like to thank Andrew
Dwyer, Sof Andrikopoulos, Cecile King, James Cantley, and Don Chisholm
for helpful comments; Amber Johns for assistance with the human
pancreatic slides; Alice Boulghourjian from the Garvan histology-core;
Will Hughes from the Garvan microscope-core; Ed Feener from the Joslin
Proteomics Core Facility DERC; staff at BTF for maintaining the mice;
and Tina Patel and Lindy Williams from Westmead and Lina Mariana from
St. Vincent's Melbourne for human islet isolations.
NR 79
TC 85
Z9 87
U1 0
U2 10
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD JUN
PY 2010
VL 120
IS 6
BP 2171
EP 2183
DI 10.1172/JCI35846
PG 13
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 605CH
UT WOS:000278324400038
PM 20440072
ER
PT J
AU Wilson, C
Huang, CC
Shara, N
Howard, BV
Fleg, JL
Henderson, JA
Howard, WJ
Huentelman, H
Lee, ET
Mete, M
Russell, M
Galloway, JM
Silverman, A
Stylianou, M
Umans, J
Weir, MR
Yeh, F
Ratner, RE
AF Wilson, Charlton
Huang, Chun-Chih
Shara, Nawar
Howard, Barbara V.
Fleg, Jerome L.
Henderson, Jeffrey A.
Howard, Wm. James
Huentelman, Heather
Lee, Elisa T.
Mete, Mihriye
Russell, Marie
Galloway, James M.
Silverman, Angela
Stylianou, Mario
Umans, Jason
Weir, Matthew R.
Yeh, Fawn
Ratner, Robert E.
TI Cost-effectiveness of lower targets for blood pressure and low-density
lipoprotein cholesterol in diabetes: The Stop Atherosclerosis in Native
Diabetics Study (SANDS)
SO JOURNAL OF CLINICAL LIPIDOLOGY
LA English
DT Article
DE Cost effectiveness; Diabetes mellitus; Lipids; Blood pressure; Quality
of well being; Clinical trial
ID CORONARY-HEART-DISEASE; TREATMENT PANEL-III; CARDIOVASCULAR-DISEASE;
RANDOMIZED-TRIAL; MELLITUS; HYPERTENSION; PREVENTION; MORTALITY;
INTERVENTIONS; ATORVASTATIN
AB BACKGROUND: The Stop Atherosclerosis in Native Diabetics Study (SANDS) reported cardiovascular benefit of aggressive versus standard treatment targets for both low-density lipoprotein Cholesterol (LDL-C) and blood pressure (BP) in diabetic individuals
OBJECTIVE: In this analysis. we examined within trial cost-effectiveness of aggressive targets of LDL-C <= 70 mg/dL and systolic BP <= 115 mmHg versus standard targets of LDL-C <= 100 mg/dL and systolic BP <= 130 mmHg
DESIGN: Randomized, open label blinded-to-endpoint 3-year trial
DATA SOURCES: SANDS clinical trial database, Quality of Wellbeing survey, Centers for Medicare and Medicaid Services, Wholesale Drug Prices
TARGET POPULATION: American Indians >= age 40 years with type 2 diabetes and no previous cardiovascular events
TIME HORIZON: April 2003 to July 2007
PERSPECTIVE: Health payer
INTERVENTIONS: Participants were randomized to aggressive versus standard groups with treatment algorithms defined for both.
OUTCOME MEASURES: Incremental cost-effectiveness
RESULTS OF BASE-CASE ANALYSIS: Compared with the standard group, the aggressive atom) had slightly lower costs of medical services (-$116) but a 54% greater cost for BP medication ($1,242) and a 116% greater cost for lipid-lowering medication ($2,863). resulting in an increased cost of $3.988 over 3 years Those in the aggressively treated group gained 0 0480 quality-adjusted life-years (QALY) over the standard group When a 3% discount rate or costs and outcomes was used, the resulting cost per QALY was $82,589
RESULTS OF SENSITIVITY ANALYSIS: The use of a 25%, 50%, and 75% reduction in drug costs resulted in a cost per QALY of $61.329, $40,070. and $18,810, respectively
LIMITATIONS: This study was limited by use of a single ethnic group and by its 3-year duration
CONCLUSIONS: Within this 3-year study. treatment to lower BP and LDL-C below standard targets was not cost-effective because of the cost of the additional medications required to meet the lower targets With the anticipated availability of generic versions of the BP and lipid-lowering drugs used in SANDS, the cost-effectiveness of this intervention should improve Published by Elsevier Inc on behalf of the National Lipid Association
C1 [Wilson, Charlton; Huentelman, Heather; Russell, Marie] Phoenix Indian Med Ctr, Phoenix, AZ 85016 USA.
[Huang, Chun-Chih; Shara, Nawar; Howard, Barbara V.; Mete, Mihriye; Silverman, Angela; Umans, Jason; Ratner, Robert E.] MedStar Res Inst, Hyattsville, MD USA.
[Fleg, Jerome L.; Stylianou, Mario] NHLBI, Bethesda, MD 20892 USA.
[Henderson, Jeffrey A.] Black Hills Ctr Amer Indian Hlth, Rapid City, SD USA.
[Howard, Barbara V.] Washington Hosp Ctr, Washington, DC 20010 USA.
[Lee, Elisa T.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
[Galloway, James M.; Yeh, Fawn] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Weir, Matthew R.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
RP Wilson, C (reprint author), Phoenix Indian Med Ctr, 4212 N 16th St, Phoenix, AZ 85016 USA.
FU National Heart, Lung, and Blood Institute, National Institutes of
Health, NHLBI [1U01 HL67031-01A1]; First Horizon Pharmacy; Triglide;
Merck and Co. Cozaar/Hyzaar; Pfizer, Inc; AstraZeneca; Schering-Plough;
Reliant; Abbott; Danchi Sankyo; Bayhill Therapeutics; Boehringer
Ingelheim; GlaxoSmithKline; NovoNordisk; Takeda; Veraligh
FX Funding was provided by the National Heart, Lung, and Blood Institute,
National Institutes of Health, NHLBI grant #1U01 HL67031-01A1
Medications were donated by First Horizon Pharmacy, Triglide, Merck and
Co. Cozaar/Hyzaar; and Pfizer, Inc. Lipitor. Dr B V Howard has served on
the advisory boards of Merck, Schering Plough, the Egg Nutrition
Council, and General Mills and has received research support from Merck
and Pfizer. Dr Wm. J. Howard has received research support from Pfizer,
AstraZeneca, Merck, and Schering-Plough, has served as a consultant for
Merck, Schering-Plough, Pfizer, and Reliant, and has served on the
Speakers' Bureaus for Merck, Schering-Plough, Pfizer, AstraZeneca,
Abbott, and Danchi Sankyo Dr Ratner has received research support from
AstraZeneca, Bayhill Therapeutics, Boehringer Ingelheim,
GlaxoSmithKline, Merck, NovoNordisk, Pfizer, Takeda, and Veraligh; has
served on the advisory boards of Amylin, AstaZeneca, ElliLilly,
GlaxoSmith Kline, Lifescan, NovoNordisk, Sanofi-Aventis, Takeda, and
Tethys Bioscience, and owns stock in Merck, Johnson & Johnson, and
Abbott. Dr Weir has served on the speaker's bureau for Merck Sharp &
Dohme, Novartis, Boehringer Ingelheim, and Bristol-Myers Squibb. He is a
scientific advisor for Amen, Novartis, MSD, Boehringer-Ingelheim,
Danchi-Sankyo, and Nicox
NR 31
TC 5
Z9 5
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1933-2874
J9 J CLIN LIPIDOL
JI J. Clin. Lipidol.
PD JUN
PY 2010
VL 4
IS 3
BP 165
EP 172
DI 10.1016/j.jacl.2010.01.008
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 599XI
UT WOS:000277947100005
PM 20563294
ER
PT J
AU Siegel, MO
Fedorko, DP
Drake, SK
Calhoun, LB
Holland, SM
AF Siegel, Marc O.
Fedorko, Daniel P.
Drake, Steven K.
Calhoun, Leslie B.
Holland, Steven M.
TI Legionella feeleii Serotype 2 Pneumonia in a Man with Chronic
Lymphocytic Leukemia: a Challenging Diagnosis
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID DESORPTION IONIZATION-TIME; FLIGHT MASS-SPECTROMETRY; RAPID
IDENTIFICATION; MIP GENE; PNEUMOPHILA; CHYLOTHORAX; INFECTION; CULTURE;
PCR; BACTERIA
AB Legionella feeleii has rarely been reported as causing pneumonia in patients with hematologic malignancies. We present a case of Legionella feeleii serotype 2 pneumonia with empyema in a man with chronic lymphocytic leukemia and describe the methods of identifying this organism using both standard methods and newer diagnostic techniques.
C1 [Siegel, Marc O.] George Washington Univ, Med Ctr, Div Infect Dis, Washington, DC 20037 USA.
[Fedorko, Daniel P.; Drake, Steven K.; Calhoun, Leslie B.] NIH, Dept Lab Med, Mark O Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
[Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Siegel, MO (reprint author), George Washington Univ, Med Ctr, Div Infect Dis, 2150 Penn Ave NW, Washington, DC 20037 USA.
EM msiegel@mfa.gwu.edu
NR 32
TC 4
Z9 5
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD JUN
PY 2010
VL 48
IS 6
BP 2294
EP 2297
DI 10.1128/JCM.00176-10
PG 4
WC Microbiology
SC Microbiology
GA 602DG
UT WOS:000278118100056
PM 20357216
ER
PT J
AU Chaturvedi, AK
Caporaso, NE
Katki, HA
Wong, HL
Chatterjee, N
Pine, SR
Chanock, SJ
Goedert, JJ
Engels, EA
AF Chaturvedi, Anil K.
Caporaso, Neil E.
Katki, Hormuzd A.
Wong, Hui-Lee
Chatterjee, Nilanjan
Pine, Sharon R.
Chanock, Stephen J.
Goedert, James J.
Engels, Eric A.
TI C-Reactive Protein and Risk of Lung Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID OBSTRUCTIVE PULMONARY-DISEASE; GLOBAL CARDIOVASCULAR RISK; EPIDEMIOLOGIC
EVIDENCE; INFLAMMATION; ASSOCIATION; PREDICTION; COHORT; POLYMORPHISMS;
METAANALYSIS; SURVIVAL
AB Purpose
Chronic inflammation could play a role in lung carcinogenesis, underscoring the potential for lung cancer prevention and screening. We investigated the association of circulating high-sensitivity C-reactive protein (CRP, an inflammation biomarker) and CRP single nucleotide polymorphisms (SNPs) with prospective lung cancer risk.
Patients and Methods
We conducted a nested case-control study of 592 lung cancer patients and 670 controls with available prediagnostic serum and 378 patients and 447 controls with DNA within the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (N = 77,464). Controls were matched to patients on age, sex, entry year, follow-up time, and smoking. We measured CRP levels in baseline serum samples and genotyped five common CRP SNPs.
Results
Elevated CRP levels were associated with increased lung cancer risk ( odds ratio [OR], 1.98; 95% CI, 1.35 to 2.89; P-trend < .001 for fourth quartile [Q4, >= 5.6 mg/L] v Q1 [< 1.0 mg/L]). The CRP association did not differ significantly by histology, follow-up time, or smoking status, but was most apparent for squamous cell carcinomas (OR, 2.92; 95% CI, 1.30 to 6.54), 2 to 5 years before lung cancer diagnosis (OR, 2.33; 95% CI, 1.24 to 4.39), and among former smokers (OR, 2.48; 95% CI, 1.53 to 4.03) and current smokers (OR, 1.90; 95% CI, 1.06 to 3.41). Although CRP SNPs and haplotypes were associated with CRP levels, they were not associated with lung cancer risk. Ten-year standardized absolute risks of lung cancer were higher with elevated CRP levels among former smokers (Q4: 2.55%; 95% CI, 1.98% to 3.27% v Q1: 1.39%; 95% CI, 1.07% to 1.81%) and current smokers (Q4: 7.37%; 95% CI, 5.81% to 9.33% v Q1: 4.03%; 95% CI, 3.01% to 5.40%).
Conclusion
Elevated CRP levels are associated with subsequently increased lung cancer risk, suggesting an etiologic role for chronic pulmonary inflammation in lung carcinogenesis. J Clin Oncol 28:2719-2726. Published by the American Society of Clinical Oncology
C1 [Chaturvedi, Anil K.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
RP Chaturvedi, AK (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 7072, Rockville, MD 20852 USA.
EM chaturva@mail.nih.gov
RI Katki, Hormuzd/B-4003-2015; Chaturvedi, Anil/J-2024-2015
OI Chaturvedi, Anil/0000-0003-2696-8899
FU National Institutes of Health; National Cancer Institute
FX Supported by the Intramural Research Program of the National Institutes
of Health, National Cancer Institute.
NR 39
TC 86
Z9 87
U1 0
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUN 1
PY 2010
VL 28
IS 16
BP 2719
EP 2726
DI 10.1200/JCO.2009.27.0454
PG 8
WC Oncology
SC Oncology
GA 601ZV
UT WOS:000278108800011
PM 20421535
ER
PT J
AU Hammond, MEH
Hayes, DF
Dowsett, M
Allred, DC
Hagerty, KL
Badve, S
Fitzgibbons, PL
Francis, G
Goldstein, NS
Hayes, M
Hicks, DG
Lester, S
Love, R
Mangu, PB
McShane, L
Miller, K
Osborne, CK
Paik, S
Perlmutter, J
Rhodes, A
Sasano, H
Schwartz, JN
Sweep, FCG
Taube, S
Torlakovic, EE
Valenstein, P
Viale, G
Visscher, D
Wheeler, T
Williams, RB
Wittliff, JL
Wolff, AC
AF Hammond, M. Elizabeth H.
Hayes, Daniel F.
Dowsett, Mitch
Allred, D. Craig
Hagerty, Karen L.
Badve, Sunil
Fitzgibbons, Patrick L.
Francis, Glenn
Goldstein, Neil S.
Hayes, Malcolm
Hicks, David G.
Lester, Susan
Love, Richard
Mangu, Pamela B.
McShane, Lisa
Miller, Keith
Osborne, C. Kent
Paik, Soonmyung
Perlmutter, Jane
Rhodes, Anthony
Sasano, Hironobu
Schwartz, Jared N.
Sweep, Fred C. G.
Taube, Sheila
Torlakovic, Emina Emilia
Valenstein, Paul
Viale, Giuseppe
Visscher, Daniel
Wheeler, Thomas
Williams, R. Bruce
Wittliff, James L.
Wolff, Antonio C.
TI American Society of Clinical Oncology/College of American Pathologists
Guideline Recommendations for Immunohistochemical Testing of Estrogen
and Progesterone Receptors in Breast Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID CENTRALLY REVIEWED EXPRESSION; LIGAND-BINDING ASSAY; PREDICTING
RESPONSE; FORMALIN FIXATION; TAMOXIFEN; THERAPY; ISSUES; TRIAL;
RECURRENCE; SUPERIOR
AB Purpose
To develop a guideline to improve the accuracy of immunohistochemical (IHC) estrogen receptor ( ER) and progesterone receptor (PgR) testing in breast cancer and the utility of these receptors as predictive markers.
Methods
The American Society of Clinical Oncology and the College of American Pathologists convened an international Expert Panel that conducted a systematic review and evaluation of the literature in partnership with Cancer Care Ontario and developed recommendations for optimal IHC ER/PgR testing performance.
Results
Up to 20% of current IHC determinations of ER and PgR testing worldwide may be inaccurate ( false negative or false positive). Most of the issues with testing have occurred because of variation in preanalytic variables, thresholds for positivity, and interpretation criteria.
Recommendations
The Panel recommends that ER and PgR status be determined on all invasive breast cancers and breast cancer recurrences. A testing algorithm that relies on accurate, reproducible assay performance is proposed. Elements to reliably reduce assay variation are specified. It is recommended that ER and PgR assays be considered positive if there are at least 1% positive tumor nuclei in the sample on testing in the presence of expected reactivity of internal ( normal epithelial elements) and external controls. The absence of benefit from endocrine therapy for women with ER-negative invasive breast cancers has been confirmed in large overviews of randomized clinical trials.
This guideline was developed through a collaboration between American Society of Clinical Oncology and College of American Pathologists and has been published jointly by invitation and consent in both the Journal of Clinical Oncology and the Archives of Pathology & Laboratory Medicine. Copyright (C) 2010 American Society of Clinical Oncology and College of American Pathologists. All rights reserved. No part of this document may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without written permission by American Society of Clinical Oncology or College of American Pathologists.
C1 Univ Utah, Sch Med, Salt Lake City, UT USA.
Washington Univ, Sch Med, St Louis, MO USA.
Univ Michigan Hlth Syst, Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI USA.
St Joseph Mercy Hosp, Georgetown, Guyana.
Gemini Grp, Ann Arbor, MI USA.
Adv Diagnost Lab, Redford, MI USA.
Presbyterian Hosp, Charlotte, NC USA.
Indiana Univ, Bloomington, IN USA.
St Jude Med Ctr, Fullerton, CA USA.
Univ Rochester, Rochester, NY USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
NCI, Bethesda, MD 20892 USA.
ST Consulting, Glen Echo, MD USA.
Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
Ohio State Univ, Columbus, OH 43210 USA.
Baylor Coll Med, Houston, TX 77030 USA.
Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA.
Delta Pathol Grp, Shreveport, LA USA.
Univ Louisville, Louisville, KY 40292 USA.
Royal Marsden Hosp, London, England.
United Kingdom Natl External Qual Assessment Serv, Sheffield, S Yorkshire, England.
Univ W England, Bristol BS16 1QY, Avon, England.
Princess Alexandra Hosp, Brisbane, Qld 4102, Australia.
Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
Royal Univ Hosp, Saskatoon, SK S7N 0W8, Canada.
Tohoku Univ, Sch Med, Sendai, Miyagi 980, Japan.
Radboud Univ Nijmegen, NL-6525 ED Nijmegen, Netherlands.
European Inst Oncol, Milan, Italy.
Univ Milan, Milan, Italy.
[Hammond, M. Elizabeth H.] ASCO, Alexandria, VA 22314 USA.
RP Hammond, MEH (reprint author), ASCO, 2318 Mill Rd,Suite 800, Alexandria, VA 22314 USA.
EM guidelines@asco.org
RI Sweep, C.G.J./H-8096-2014; Rhodes, Anthony/O-9062-2014; Wolff,
A.P./L-4767-2015;
OI Rhodes, Anthony/0000-0002-1187-0939; Fitzgibbons,
Patrick/0000-0002-2998-6913; Wolff, Antonio/0000-0003-3734-1063
FU Hironobu Sasano, Ventana Japan
FX Research Funding: Hironobu Sasano, Ventana Japan
NR 34
TC 956
Z9 997
U1 12
U2 64
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 JUN 1
PY 2010
VL 28
IS 16
BP 2784
EP 2795
DI 10.1200/JCO.2009.25.6529
PG 12
WC Oncology
SC Oncology
GA 601ZV
UT WOS:000278108800020
PM 20404251
ER
PT J
AU Chadburn, A
Noy, A
Lee, JY
Hyjek, E
Banham, AH
Sparano, JA
Bhatia, K
Cesarman, E
AF Chadburn, Amy
Noy, Ariela
Lee, Jeannette Y.
Hyjek, Elizabeth
Banham, Alison H.
Sparano, Joseph A.
Bhatia, Kishor
Cesarman, Ethel
TI Role of Molecular Subtype in Predicting Outcome of AIDS-Related Diffuse
Large B-Cell Lymphoma Reply
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
ID PROGNOSTIC IMPACT
C1 [Chadburn, Amy; Cesarman, Ethel] Weill Cornell Med Coll, Chicago, IL USA.
[Noy, Ariela] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Lee, Jeannette Y.] Univ Arkansas Med Sci, Little Rock, AK USA.
[Hyjek, Elizabeth] Univ Chicago, Chicago, IL 60637 USA.
[Banham, Alison H.] Univ Oxford, Oxford, England.
[Sparano, Joseph A.] Albert Einstein Comprehens Canc Ctr, New York, NY USA.
[Bhatia, Kishor] NCI, NIH, Bethesda, MD 20892 USA.
RP Chadburn, A (reprint author), Weill Cornell Med Coll, Chicago, IL USA.
RI Banham, Alison/B-2966-2009
NR 12
TC 4
Z9 4
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUN 1
PY 2010
VL 28
IS 16
BP E261
EP E262
DI 10.1200/JCO.2010.28.0305
PG 2
WC Oncology
SC Oncology
GA 601ZV
UT WOS:000278108800035
ER
PT J
AU Dunleavy, K
Wilson, WH
AF Dunleavy, Kieron
Wilson, Wyndham H.
TI Role of Molecular Subtype in Predicting Outcome of AIDS-Related Diffuse
Large B-Cell Lymphoma
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
ID NON-HODGKIN-LYMPHOMA; CHEMOTHERAPY; RITUXIMAB; SURVIVAL
C1 [Dunleavy, Kieron; Wilson, Wyndham H.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Dunleavy, K (reprint author), NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
NR 13
TC 7
Z9 7
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 JUN 1
PY 2010
VL 28
IS 16
BP E260
EP E260
DI 10.1200/JCO.2009.27.7087
PG 1
WC Oncology
SC Oncology
GA 601ZV
UT WOS:000278108800034
PM 20421532
ER
PT J
AU Postman-Caucheteux, WA
Birn, RM
Pursley, RH
Butman, JA
Solomon, JM
Picchioni, D
McArdle, J
Braun, AR
AF Postman-Caucheteux, Whitney Anne
Birn, Rasmus M.
Pursley, Randall H.
Butman, John A.
Solomon, Jeffrey M.
Picchioni, Dante
McArdle, Joe
Braun, Allen R.
TI Single-trial fMRI Shows Contralesional Activity Linked to Overt Naming
Errors in Chronic Aphasic Patients
SO JOURNAL OF COGNITIVE NEUROSCIENCE
LA English
DT Article
ID POSITRON-EMISSION-TOMOGRAPHY; FUNCTIONAL MRI; LANGUAGE ACTIVATION;
POSTSTROKE APHASIA; NONFLUENT APHASIA; TASK-DIFFICULTY; WORD PRODUCTION;
FRONTAL-CORTEX; LEXICAL ACCESS; RECOVERY
AB We used fMRI to investigate the roles played by perilesional and contralesional cortical regions during language production in stroke patients with chronic aphasia. We applied comprehensive psycholinguistic analyses based on well-established models of lexical access to overt picture-naming responses, which were evaluated using a single trial design that permitted distinction between correct and incorrect responses on a trial-by-trial basis. Although both correct and incorrect naming responses were associated with left-sided perilesional activation, incorrect responses were selectively associated with robust right-sided contralesional activity. Most notably, incorrect responses elicited overactivation in the right inferior frontal gyrus that was not observed in the contrasts for patients' correct responses or for responses of age-matched control subjects. Errors were produced at slightly later onsets than accurate responses and comprised predominantly semantic paraphasias and omissions. Both types of errors were induced by pictures with greater numbers of alternative names, and omissions were also induced by pictures with late acquired names. These two factors, number of alternative names per picture and age of acquisition, were positively correlated with activation in left and right inferior frontal gyri in patients as well as control subjects. These results support the hypothesis that some right frontal activation may normally be associated with increasing naming difficulty, but in patients with aphasia, right frontal overactivation may reflect ineffective effort when left hemisphere perilesional resources are insufficient. They also suggest that contralesional areas continue to play a role-dysfunctional rather than compensatory-in chronic aphasic patients who have experienced a significant degree of recovery.
C1 [Postman-Caucheteux, Whitney Anne; Birn, Rasmus M.; Pursley, Randall H.; Butman, John A.; McArdle, Joe; Braun, Allen R.] NIH, Bethesda, MD 20892 USA.
[Solomon, Jeffrey M.] Med Numer Inc, Germantown, MD USA.
[Picchioni, Dante] Walter Reed Army Inst Res, Silver Spring, MD USA.
RP Postman-Caucheteux, WA (reprint author), Temple Univ, Dept Commun Sci & Disorders, 110 Weiss Hall,1701 N 13th St, Philadelphia, PA 19122 USA.
EM whitneyanne@alum.mit.edu
RI Butman, John/A-2694-2008; Butman, John/J-2780-2013
OI Butman, John/0000-0002-1547-9195
FU John Pluta and the Center for Functional Neuroimaging at the University
of Pennsylvania [NS045839]
FX This work was supported by the Intramural Program of the National
Institute on Deafness and Other Communication Disorders. We gratefully
acknowledge the invaluable comments, critiques, and suggestions from
three anonymous reviewers. The first author acknowledges John Pluta and
the Center for Functional Neuroimaging at the University of Pennsylvania
(NS045839) for support during the revision phase of this manuscript, and
is indebted to Patricia Sokolove, Alex Martin and Bob Loeffler for their
guidance and encouragement.
NR 52
TC 62
Z9 67
U1 1
U2 6
PU MIT PRESS
PI CAMBRIDGE
PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA
SN 0898-929X
J9 J COGNITIVE NEUROSCI
JI J. Cogn. Neurosci.
PD JUN
PY 2010
VL 22
IS 6
BP 1299
EP 1318
DI 10.1162/jocn.2009.21261
PG 20
WC Neurosciences; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA 572XG
UT WOS:000275869700019
PM 19413476
ER
PT J
AU Sitzmann, M
Ihlenfeldt, WD
Nicklaus, MC
AF Sitzmann, Markus
Ihlenfeldt, Wolf-Dietrich
Nicklaus, Marc C.
TI Tautomerism in large databases
SO JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
LA English
DT Article
DE Database; Tautomers; Stereochemistry; Chemoinformatics; Small molecules
ID ENUMERATION; PREDICTION; EQUILIBRIA; MOLECULES; DESIGN; CACTVS
AB We have used the Chemical Structure DataBase (CSDB) of the NCI CADD Group, an aggregated collection of over 150 small-molecule databases totaling 103.5 million structure records, to conduct tautomerism analyses on one of the largest currently existing sets of real (i.e. not computer-generated) compounds. This analysis was carried out using calculable chemical structure identifiers developed by the NCI CADD Group, based on hash codes available in the chemoinformatics toolkit CACTVS and a newly developed scoring scheme to define a canonical tautomer for any encountered structure. CACTVS's tautomerism definition, a set of 21 transform rules expressed in SMIRKS line notation, was used, which takes a comprehensive stance as to the possible types of tautomeric interconversion included. Tautomerism was found to be possible for more than 2/3 of the unique structures in the CSDB. A total of 680 million tautomers were calculated from, and including, the original structure records. Tautomerism overlap within the same individual database (i.e. at least one other entry was present that was really only a different tautomeric representation of the same compound) was found at an average rate of 0.3% of the original structure records, with values as high as nearly 2% for some of the databases in CSDB. Projected onto the set of unique structures (by FICuS identifier), this still occurred in about 1.5% of the cases. Tautomeric overlap across all constituent databases in CSDB was found for nearly 10% of the records in the collection.
C1 [Sitzmann, Markus; Nicklaus, Marc C.] NCI, Biol Chem Lab, Ctr Canc Res, NIH,DHHS, Frederick, MD 21702 USA.
[Ihlenfeldt, Wolf-Dietrich] Xemistry GmbH, D-61462 Konigstein, Germany.
RP Nicklaus, MC (reprint author), NCI, Biol Chem 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
NR 24
TC 19
Z9 19
U1 2
U2 7
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0920-654X
J9 J COMPUT AID MOL DES
JI J. Comput.-Aided Mol. Des.
PD JUN
PY 2010
VL 24
IS 6-7
BP 521
EP 551
DI 10.1007/s10822-010-9346-4
PG 31
WC Biochemistry & Molecular Biology; Biophysics; Computer Science,
Interdisciplinary Applications
SC Biochemistry & Molecular Biology; Biophysics; Computer Science
GA 612JR
UT WOS:000278894800005
PM 20512400
ER
PT J
AU Strunk, DR
Brotman, MA
DeRubeis, RJ
Hollon, SD
AF Strunk, Daniel R.
Brotman, Melissa A.
DeRubeis, Robert J.
Hollon, Steven D.
TI Therapist Competence in Cognitive Therapy for Depression: Predicting
Subsequent Symptom Change
SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY
LA English
DT Article
DE cognitive therapy; depression; competence; therapist
ID MEDICATIONS; DISORDER; MODERATE; SCALE
AB Objective: The efficacy of cognitive therapy (CT) for depression has been well established. Measures of the adequacy of therapists' delivery of treatment are critical to facilitating therapist training and treatment dissemination. While some studies have shown an association between CT competence and outcome, researchers have yet to address whether competence ratings predict subsequent outcomes. Method: In a sample of 60 moderately to severely depressed outpatients from a clinical trial, we examined competence ratings (using the Cognitive Therapy Scale) as a predictor of subsequent symptom change. Results: Competence ratings predicted session-to-session symptom change early in treatment. In analyses focused on prediction of symptom change following 4 early sessions through the end of 16 weeks of treatment, competence was shown to be a significant predictor of evaluator-rated end-of-treatment depressive symptom severity and was predictive of self-reported symptom severity at the level of a nonsignificant trend. To investigate whether competence is more important to clients with specific complicating features, we examined 4 patient characteristics as potential moderators of the competence-outcome relation. Competence was more highly related to subsequent outcome for patients with higher anxiety, an earlier age of onset, and (at a trend level) patients with a chronic form of depression (chronic depression or dysthymia) than for those patients without these characteristics. Competence ratings were not more predictive of subsequent outcomes among patients who met (vs. those who did not meet) criteria for a personality disorder (i.e., among personality disorders represented in the clinical trial). Conclusions: These findings provide support for the potential utility of CT competence ratings in applied settings.
C1 [Strunk, Daniel R.] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA.
[Brotman, Melissa A.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD USA.
[DeRubeis, Robert J.] Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA.
[Hollon, Steven D.] Vanderbilt Univ, Dept Psychol, Nashville, TN USA.
RP Strunk, DR (reprint author), Ohio State Univ, Dept Psychol, 1835 Neil Ave, Columbus, OH 43210 USA.
EM strunk.20@osu.edu
RI Brotman, Melissa/H-7409-2013; Strunk, Daniel/F-4153-2011
OI Strunk, Daniel/0000-0002-7444-0741
FU NIMH NIH HHS [R10 MH55875, K02 MH001697, K02 MH001697-01A1, K02
MH01697, K24 MH001741, K24 MH001741-01, K24 MH01741, R10 MH055875, R10
MH055875-04, R10 MH055877, R10 MH055877-04, R10 MH55877]
NR 34
TC 49
Z9 50
U1 5
U2 22
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0022-006X
J9 J CONSULT CLIN PSYCH
JI J. Consult. Clin. Psychol.
PD JUN
PY 2010
VL 78
IS 3
BP 429
EP 437
DI 10.1037/a0019631
PG 9
WC Psychology, Clinical
SC Psychology
GA 606GX
UT WOS:000278412000014
PM 20515218
ER
PT J
AU Schwerin, M
Schonfeld, S
Drozdovitch, V
Akimzhanov, K
Aldyngurov, D
Bouville, A
Land, C
Luckyanov, N
Mabuchi, K
Semenova, Y
Simon, S
Tokaeva, A
Zhumadilov, Z
Potischman, N
AF Schwerin, M.
Schonfeld, S.
Drozdovitch, V.
Akimzhanov, K.
Aldyngurov, D.
Bouville, A.
Land, C.
Luckyanov, N.
Mabuchi, K.
Semenova, Y.
Simon, S.
Tokaeva, A.
Zhumadilov, Z.
Potischman, N.
TI The utility of focus group interviews to capture dietary consumption
data in the distant past: dairy consumption in Kazakhstan villages 50
years ago
SO JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE
LA English
DT Article
DE diet; epidemiology; focus group interview; Kazakhstan; older
respondents; radiation exposure
ID SELF-REFERENCE; ADOLESCENT DIET; FOOD-CONSUMPTION; AMERICAN WOMEN;
NUCLEAR TESTS; RECALL; REPRODUCIBILITY; INFORMATION; RELIABILITY; MEMORY
AB From 1949 to 1962, residents of several villages in Kazakhstan received substantial doses of radiation to the thyroid gland resulting from nuclear tests conducted at the Semipalatinsk Nuclear Test Site. The primary source of radiation was internal from an intake of radioactive iodine by consumption of contaminated dairy products. A previous research study of childhood exposure and thyroid disease in this region gathered limited data on study participants' dairy intake at the time of the fallout for the purpose of estimating past radiation doses. As many participants were too young at the time of the nuclear tests to recall dietary consumption and existing sources of archival data are limited, it was necessary to interview parents and other village residents who cared for children during this time - older adults ranging in age from 75 to 90 years. Results from 11 focus group interviews conducted in 2007 with 82 women from 4 villages in Kazakhstan yielded group-level estimates of age-, gender-, ethnicity-and village-specific dairy consumption patterns in rural Kazakhstan during the 1950s. Children typically consumed cow's milk with limited consumption of mare, goat and sheep milk; and consumed dairy products such as sour milk (airan), soft cottage cheese (tvorog) and fermented mare milk (koumiss) with the greatest amounts of koumiss reported at ages 15-21 years. The consumption patterns differed by age, and between Kazakh and Russian children, which should lead to different estimates of radiation exposure to the thyroid. This study showed the utility of focus groups to obtain quantitative estimates for dietary intake in the distant past.
C1 [Schwerin, M.] RTI Int, Res Triangle Pk, NC 27709 USA.
[Schonfeld, S.; Drozdovitch, V.; Bouville, A.; Land, C.; Luckyanov, N.; Mabuchi, K.; Simon, S.; Potischman, N.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Akimzhanov, K.; Aldyngurov, D.; Semenova, Y.; Tokaeva, A.; Zhumadilov, Z.] Govt Semipalatinsk State Med Univ, Semipalatinsk, Kazakhstan.
RP Schwerin, M (reprint author), RTI Int, 3040 Cornwallis Rd, Res Triangle Pk, NC 27709 USA.
EM schwerin@rti.org
FU National Cancer Institute
FX The authors acknowledge the participants of their focus group
interviews, medical officials and civil officials in Karaul, Kainar,
Dolon, Kanonerka, Sarzhal, Korostely, Novopokrovka and Bolshaya
Vladimirovka who aided in the field study in August-September 2007. The
authors also acknowledge support and guidance from Dr Martha Linet of
the National Cancer Institute and Ms Kim Aspinwall, Ms Dawn Ohse, Ms
Norma Kim and Mr John Heinrich from RTI International. The authors thank
Dr Deukwoo Kwon of the National Cancer Institute for statistical
support. The authors extend their gratitude and appreciation to the
anonymous reviewers for their constructive feedback.
NR 56
TC 5
Z9 5
U1 0
U2 13
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 2040-1744
J9 J DEV ORIG HLTH DIS
JI J. Dev. Orig. Health Dis.
PD JUN
PY 2010
VL 1
IS 3
BP 192
EP 202
DI 10.1017/S2040174410000243
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 755DH
UT WOS:000289906400006
PM 24286002
ER
PT J
AU Fiellin, D
Vogenthaler, N
Bryant, K
Goulet, J
McGinnis, K
Mattocks, K
Leaf, D
Gilbert, C
Wang, E
Sullivan, L
Justice, A
AF Fiellin, David
Vogenthaler, Nicholas
Bryant, Kendall
Goulet, Joseph
McGinnis, Kathleen
Mattocks, Kristin
Leaf, David
Gilbert, Cynthia
Wang, Emily
Sullivan, Lynn
Justice, Amy
TI FOOD INSECURITY IS ASSOCIATED WITH POOR IMMUNOLOGIC AND VIROLOGIC
RESPONSE AMONG HIV-INFECTED PATIENTS
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine
CY APR 18-MAY 01, 2010
CL Minneapolis, MN
SP Soc Gen Internal Med
C1 [Fiellin, David; Wang, Emily; Sullivan, Lynn; Justice, Amy] Yale Univ, Sch Med, New Haven, CT 30322 USA.
[Vogenthaler, Nicholas] Emory Univ, Sch Med, Atlanta, GA USA.
[Bryant, Kendall] NIAAA, Off Collaborat Res, Bethesda, MD USA.
[Goulet, Joseph; McGinnis, Kathleen; Mattocks, Kristin] VA Connecticut Healthcare Syst, West Haven, CT USA.
[Leaf, David] Vet Affairs Greater Angeles Healthcare Syst, Los Angeles, CA 20422 USA.
[Gilbert, Cynthia] Vet Affairs Med Ctr, Washington, DC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD JUN
PY 2010
VL 25
SU 3
BP 281
EP 281
PG 1
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 591EO
UT WOS:000277282300172
ER
PT J
AU Jolly, S
Wang, H
Mete, M
Devereux, R
Howard, BV
Umans, J
Fabsitz, R
Ebbesson, S
Adar, SE
AF Jolly, Stacey
Wang, Hong
Mete, Mihriye
Devereux, Richard
Howard, Barbara V.
Umans, Jason
Fabsitz, Richard
Ebbesson, Sven
Adar, Sigal Eilat
TI NUTRITIONAL FACTORS ASSOCIATED WITH HYPERTENSION AMONG ALASKA ESKIMOS
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine
CY APR 18-MAY 01, 2010
CL Minneapolis, MN
SP Soc Gen Internal Med
C1 [Jolly, Stacey] Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA.
[Wang, Hong; Mete, Mihriye] Dept Epidemiol & Stat, Hyattsville, MD USA.
[Devereux, Richard] Greenberg Div Cardiol, New York, NY USA.
[Howard, Barbara V.] MedStar Res Inst, Hyattsville, MD USA.
[Umans, Jason] MedStar Res Inst, Washington, DC USA.
[Fabsitz, Richard] NHLBI, Bethesda, MD 20892 USA.
[Ebbesson, Sven] Norton Sound Hlth Corp, Fairbanks, AK USA.
[Adar, Sigal Eilat] Zinman Coll Phys Educ & Sports, Jerusalem, Israel.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD JUN
PY 2010
VL 25
SU 3
BP 338
EP 339
PG 2
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 591EO
UT WOS:000277282300289
ER
PT J
AU Bautista, M
Kwoh, CK
Harris, T
Simonsick, E
Beyth, R
Shorr, R
Nevitt, M
Garvan, C
Satterfield, S
AF Bautista, Miho
Kwoh, C. Kent
Harris, Tamara
Simonsick, Eleanor
Beyth, Rebecca
Shorr, Ronald
Nevitt, Michael
Garvan, Cynthia
Satterfield, Suzanne
TI SITE DIFFERENCE IN THE UTILIZATION OF TOTAL KNEE ARTHROPLASTY IN OLDER
ADULTS WITH KNEE PAIN: FINDINGS FROM THE HEALTH, AGING AND BODY
COMPOSITION STUDY
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the Society-of-General-Internal-Medicine
CY APR 18-MAY 01, 2010
CL Minneapolis, MN
SP Soc Gen Internal Med
C1 [Bautista, Miho; Beyth, Rebecca] GRECC, NF SGVHS, Gainesville, FL USA.
[Kwoh, C. Kent] Univ Pittsburgh, Pittsburgh, PA USA.
[Kwoh, C. Kent] Pittsburgh VA Hlth System, CHERP, Pittsburgh, PA USA.
[Harris, Tamara; Simonsick, Eleanor] Natl Inst Aging, NIH, Bethesda, MD USA.
[Nevitt, Michael] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Garvan, Cynthia] Univ Florida, Coll Educ, Gainesville, FL USA.
[Satterfield, Suzanne] Univ Tennessee, Memphis, TN USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD JUN
PY 2010
VL 25
SU 3
BP 390
EP 391
PG 2
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 591EO
UT WOS:000277282300407
ER
PT J
AU Pervez, MM
Cobb, B
Matin, N
Shahrin, L
Ford, ER
Pietroni, M
AF Pervez, Md. Moshtaq
Cobb, Brian
Matin, Nashaba
Shahrin, Lubaba
Ford, Evelyn R.
Pietroni, Mark
TI Disseminated Histoplasmosis in a Patient with Advanced HIV
Disease-Lessons Learnt from Bangladesh
SO JOURNAL OF HEALTH POPULATION AND NUTRITION
LA English
DT Article
DE Case studies; Histoplasma capsulatum; Histoplasmosis; HIV; Tuberculosis;
Bangladesh
ID INFECTION
AB Histoplasmosis is a systemic fungal disease, also known as Darling's disease, caused by the dimorphic fungus Histoplasma capsulatum. It is usually self-limiting or localized in immunecompetent individuals whereas in patients with acquired immune deficiency syndrome (AIDS), it occurs in the disseminated form in 95% of cases. Although histoplasmosis predominates in the Americas (United States and Latin America, including Brazil) as an important infection among AIDS patients, it is not common in Bangladesh. In contrast, tuberculosis is extremely common in Bangladesh, with an estimated prevalence of 387 per 100,000 people. Here, a confirmed case of disseminated histoplasmosis is reported in Bangladesh in a known HIV-positive patient, which was initially suspected to be extrapulmonary tuberculosis.
C1 [Pervez, Md. Moshtaq] ICDDR B, Execut Directors Div, Dhaka Hosp, Dhaka 1000, Bangladesh.
[Ford, Evelyn R.] Vanderbilt Univ, NIH, Fogarty Int Clin Res Scholars Program, Inst Global Hlth, Nashville, TN 37203 USA.
RP Pervez, MM (reprint author), ICDDR B, Execut Directors Div, Dhaka Hosp, GPO Box 128, Dhaka 1000, Bangladesh.
EM pervez@icddrb.org
NR 12
TC 4
Z9 4
U1 0
U2 0
PU I C D D R B-CENTRE HEALTH POPULATION RESEARCH
PI DHAKA
PA MOHAKHALI, 1212 DHAKA, BANGLADESH
SN 1606-0997
J9 J HEALTH POPUL NUTR
JI J. Heatlh Popul. Nutr.
PD JUN
PY 2010
VL 28
IS 3
BP 305
EP 307
PG 3
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA 623RG
UT WOS:000279758900014
PM 20635643
ER
PT J
AU Shankaran, S
Bann, CM
Bauer, CR
Lester, BM
Bada, HS
Das, A
Higgins, RD
Poole, WK
LaGasse, LL
Hammond, J
Woldt, E
AF Shankaran, Seetha
Bann, Carla M.
Bauer, Charles R.
Lester, Barry M.
Bada, Henrietta S.
Das, Abhik
Higgins, Rosemary D.
Poole, W. Kenneth
LaGasse, Linda L.
Hammond, Jane
Woldt, Eunice
TI Prenatal cocaine exposure and BMI and blood pressure at 9 years of age
SO JOURNAL OF HYPERTENSION
LA English
DT Article
DE BMI; childhood hypertension; obesity; overweight; prenatal cocaine
exposure
ID INTRAUTERINE GROWTH RESTRICTION; CHILDHOOD OVERWEIGHT; DIETARY
INTERVENTION; BIRTH-WEIGHT; CHILDREN; HYPERTENSION; ADOLESCENTS;
PREGNANCY; RISK; PREVALENCE
AB Background Prenatal cocaine exposure has been linked to intrauterine growth retardation and poor birth outcomes; little is known about the effects on longer-term medical outcomes, such as overweight status and hypertension in childhood. Our objective was to examine the association between prenatal cocaine exposure and BMI and blood pressure at 9 years of age among children followed prospectively in a multisite longitudinal study evaluating the impact of maternal lifestyle during pregnancy on childhood outcome.
Design/methods This analysis includes 880 children (277 cocaine exposed and 603 with no cocaine exposure) with blood pressure, height, and weight measurements at 9 years of age. Regression analyses were conducted to explore the relationship between prenatal cocaine exposure and BMI and blood pressure at 9 years of age after controlling for demographics, other drug exposure, birth weight, maternal weight, infant postnatal weight gain, and childhood television viewing, exercise, and dietary habits at 9 years. Path analyses were used to further explore these relationships.
Results At 9 years of age, 15% of the children were prehypertensive and 19% were hypertensive; 16% were at risk for overweight status and 21% were overweight. A small percentage of women were exposed to high levels of prenatal cocaine throughout pregnancy. A higher BMI was noted in children born to these women. Path analysis suggested that high cocaine exposure has an indirect effect on systolic and diastolic blood pressures that is mediated through its effect on BMI.
Conclusion High levels of in-utero cocaine exposure are a marker for elevated BMI and blood pressure among children born full term. J Hypertens 28: 1166-1175 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Shankaran, Seetha; Woldt, Eunice] Wayne State Univ, Sch Med, Detroit, MI USA.
[Bann, Carla M.; Das, Abhik; Poole, W. Kenneth; Hammond, Jane] Res Triangle Inst Int, Rockville, MD USA.
[Bauer, Charles R.] Univ Miami, Miami, FL USA.
[Lester, Barry M.; LaGasse, Linda L.] Women & Infants Hosp Rhode Isl, Providence, RI USA.
[Bada, Henrietta S.] Univ Tennessee, Memphis, TN USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Shankaran, S (reprint author), Childrens Hosp Michigan, 3901 Beaubien Blvd, Detroit, MI 48201 USA.
EM sshankar@med.wayne.edu
FU National Institutes of Health; Eunice Kennedy Shriver National Institute
of Child Health and Human Development (NICHD); National Institute on
Drug Abuse (NIDA); Administration on Children, Youth, and Families;
Center for Substance Abuse and Treatment; [U10HD21385]; [U10HD36790];
[U10HD21397]; [U10 HD27904]; [U10HD42638]
FX The National Institutes of Health, the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD), the National
Institute on Drug Abuse (NIDA), the Administration on Children, Youth,
and Families, and the Center for Substance Abuse and Treatment provided
grant support for recruiting subjects into the Maternal Lifestyle Study
in 1993-1995. NIDA and NICHD provided funding to conduct follow-up
examinations in three phases: at 1, 4, 8, 10, 12, 18, 24, and 36 months
corrected age (Phase I); at 3.5, 4, 4.5, 5, 5.5, 6, and 7 years of age
(Phase II); and at 8, 9, 10, and 11 years of age (Phase III). The
funding agencies provided overall oversight of study conduct, but all
data analyses and interpretation were completed independent of the
funding agencies. We are indebted to our medical and nursing colleagues
and the infants and their parents who agreed to take part in this
study.; Data collected at participating sites of the NICHD Neonatal
Research Network (NRN) were transmitted to RTI International, the data
coordinating center (DCC) for the network, which stored, managed, and
analyzed the data for this study. On behalf of the NRN, Drs Abhik Das
(DCC Principal Investigator) and Sylvia Tan (DCC Statistician) had full
access to all the data in the study and take responsibility for the
integrity of the data and accuracy of the data analysis.; Grant numbers:
U10HD21385, U10HD36790, U10HD21397, U10 HD27904, and U10HD42638.
NR 34
TC 10
Z9 12
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0263-6352
J9 J HYPERTENS
JI J. Hypertens.
PD JUN
PY 2010
VL 28
IS 6
BP 1166
EP 1175
DI 10.1097/HJH.0b013e328337da75
PG 10
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 595PG
UT WOS:000277623500010
PM 20486281
ER
PT J
AU Fang, YJ
Deng, HB
Thomas, GN
Tzang, CH
Li, CX
Xu, ZL
Yang, MS
Tomlinson, B
AF Fang, Yu-Jing
Deng, Han-Bing
Thomas, G. Neil
Tzang, Chi H.
Li, Cai-Xia
Xu, Zong-Li
Yang, Mengsu
Tomlinson, Brian
TI Linkage of angiotensinogen gene polymorphisms with hypertension in a
sibling study of Hong Kong Chinese
SO JOURNAL OF HYPERTENSION
LA English
DT Article
DE angiotensinogen; hypertension; sibling study
ID ADIPOSE-TISSUE; BLOOD-PRESSURE; TRANSMISSION/DISEQUILIBRIUM-TEST; M235T
POLYMORPHISM; METABOLIC SYNDROME; OBESITY; TRANSMISSION; ASSOCIATION;
DISEASE; SYSTEM
AB Objective The angiotensinogen gene has been linked with human essential hypertension in whites but the relationship in Asian populations has been less consistent. This study aimed to examine genetic associations between hypertension and the M235T, T174M, and G-217A polymorphisms of the angiotensinogen gene in Chinese siblings.
Methods We studied members of 126 families with a hypertensive proband, including 434 siblings, of which 178 were hypertensive. Parental history of hypertension was recorded. The M235T, T174M, and G-217A polymorphisms were examined using a microarray method, validated by sequencing. The transmission disequilibrium test was applied to identify whether the genetic polymorphism loci were related to hypertension. Haplotype analysis of the combined polymorphisms was applied using the TRANSMIT program. Linkage study was conducted by applying the affected pedigree member method.
Results A significant overtransmission was observed for the T235 allele at the M235T polymorphism and hypertension (chi(2) = 4.41, P = 0.036) but not for the T174M and G-217A polymorphisms. The haplotype analysis showed a significant association with the haplotypes of paired markers (T174 and T235) with chi(2) value of 8.131 (P = 0.004; global test chi(2) = 9.131, P = 0.028). Linkage between M235T and hypertension was detected (T = -2.25, P = 0.019), and a tendency for linkage with central obesity-related hypertension was found for the M235T and T174M polymorphisms (P = 0.0087 and P = 0.01).
Conclusion The M235T and T174M variants, especially the T235 allele, contribute to an increased risk of hypertension in these Chinese patients. J Hypertens 28: 1203-1209 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Fang, Yu-Jing; Deng, Han-Bing; Thomas, G. Neil; Tomlinson, Brian] Chinese Univ Hong Kong, Dept Med & Therapeut, Shatin, Hong Kong, Peoples R China.
[Fang, Yu-Jing] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol S China, Dept Colorectal Surg, Guangzhou 510275, Guangdong, Peoples R China.
[Thomas, G. Neil] Univ Birmingham, Dept Epidemiol & Publ Hlth, Birmingham, W Midlands, England.
[Tzang, Chi H.; Yang, Mengsu] City Univ Hong Kong, Dept Biol & Chem, Kowloon, Hong Kong, Peoples R China.
[Li, Cai-Xia] Sun Yat Sen Univ, Dept Med Stat, Guangzhou 510275, Guangdong, Peoples R China.
[Xu, Zong-Li] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
RP Tomlinson, B (reprint author), Prince Wales Hosp, Div Clin Pharmacol, Dept Med & Therapeut, Shatin, Hong Kong, Peoples R China.
EM btomlinson@cuhk.edu.hk
RI Hossain, Sarah /C-7332-2009; Thomas, G. Neil/A-1879-2013; Yang,
Mengsu/I-5750-2015; Tomlinson, Brian/P-5365-2015;
OI Hossain, Sarah /0000-0003-1355-0979; Thomas, G.
Neil/0000-0002-2777-1847; Yang, Mengsu/0000-0003-2083-2296; Deng,
Han-Bing/0000-0003-3178-7611; xu, zongli/0000-0002-9034-8902
FU Research Grants Council of the Hong Kong Special Administrative Region,
China [CUHK 4095/00M, CUHK 4438/03M, HKU 7672/06M]
FX The work described in this paper was supported by grants from the
Research Grants Council of the Hong Kong Special Administrative Region,
China (projects no. CUHK 4095/00M, CUHK 4438/03M, and HKU 7672/06M).
This funding source had no role in the conduct of the study.
NR 40
TC 20
Z9 22
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0263-6352
J9 J HYPERTENS
JI J. Hypertens.
PD JUN
PY 2010
VL 28
IS 6
BP 1203
EP 1209
DI 10.1097/HJH.0b013e3283384b07
PG 7
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 595PG
UT WOS:000277623500014
PM 20216084
ER
PT J
AU Gu, DF
Kelly, TN
Hixson, JE
Chen, J
Liu, DP
Chen, JC
Rao, DC
Mu, JJ
Ma, JX
Jaquish, CE
Rice, TK
Gu, C
Hamm, LL
Whelton, PK
He, J
AF Gu, Dongfeng
Kelly, Tanika N.
Hixson, James E.
Chen, Jing
Liu, Depei
Chen, Ji-chun
Rao, Dabeeru C.
Mu, Jianjun
Ma, Jixiang
Jaquish, Cashell E.
Rice, Treva K.
Gu, Charles
Hamm, L. Lee
Whelton, Paul K.
He, Jiang
TI Genetic variants in the renin-angiotensin-aldosterone system and salt
sensitivity of blood pressure
SO JOURNAL OF HYPERTENSION
LA English
DT Article
DE blood pressure; dietary sodium; genetics; polymorphism;
renin-angiotensin-aldosterone system; salt sensitivity
ID ESSENTIAL-HYPERTENSION; SODIUM SENSITIVITY; BLACK-AMERICANS;
MOLECULAR-BASIS; POLYMORPHISM; ASSOCIATION; HERITABILITY; POPULATION;
EXPRESSION; CAUCASIANS
AB Objective To examine the association between renin-angiotensin-aldosterone system (RAAS) genes and salt sensitivity of blood pressure (BP).
Methods A 7-day low-sodium dietary intervention followed by a 7-day high-sodium dietary intervention was conducted among 1906 participants living in a rural region of north China where habitual sodium intake is high. BP measurements were obtained at baseline and following each intervention using a random-zero sphygmomanometer.
Results DBP and mean arterial pressure responses increased with the number of rs4524238 A alleles in the angiotensin II receptor type 1 gene. For example, mean DBP responses (95% confidence interval) among those with genotypes G/G, G/A, and A/A were -2.53 (-2.89 to -2.18), -3.49 (-4.13 to -2.86), and -5.78 (-9.51 to -2.06) mmHg, respectively, following the low-sodium intervention (P = 0.0008). Carriers of the rare A allele of rs5479 in the hydroxysteroid (11-beta) dehydrogenase 2 gene had decreased DBP responses to low sodium (P = 0.00004). Those with the C/A and C/C genotypes had DBP responses of -0.70 (-6.62 to 5.22) and -2.71 (-4.88 to -0.54) mmHg, respectively. X chromosome renin-binding protein gene markers rs1557501 and rs2269372 were associated with SBP response to low sodium in men (P = 0.00004 and 0.0001, respectively). SBP responses (95% confidence interval) were -6.13 (-6.68 to -5.58) versus -4.07 (-4.88 to -3.26) and -6.04 (-6.57 to -5.52) versus -3.94 (-4.90 to -2.99) mmHg among men with major versus those with minor alleles of rs1557501 and rs2269372, respectively. Haplotype analyses of these genes supported our single-marker findings.
Conclusion We identified renin-angiotensin-aldosterone system variants that were predictive of salt sensitivity in a Han population with habitually high-sodium intake. J Hypertens 28: 1210-1220 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Kelly, Tanika N.; He, Jiang] Tulane Univ, Dept Epidemiol, Sch Publ Hlth & Trop Med, New Orleans, LA 70112 USA.
[Gu, Dongfeng; Chen, Ji-chun] Chinese Acad Med Sci, Cardiovasc Inst, Beijing 100037, Peoples R China.
[Gu, Dongfeng; Chen, Ji-chun] Chinese Acad Med Sci, Fuwai Hosp, Beijing 100037, Peoples R China.
[Gu, Dongfeng; Liu, Depei; Chen, Ji-chun] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Gu, Dongfeng; Chen, Ji-chun] Chinese Natl Ctr Cardiovasc Dis Control & Res, Beijing, Peoples R China.
[Hixson, James E.] Univ Texas Sch Publ Hlth, Dept Epidemiol, Houston, TX USA.
[Chen, Jing; Hamm, L. Lee; He, Jiang] Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70112 USA.
[Liu, Depei] Chinese Acad Med Sci, Inst Basic Med Sci, Natl Lab Med Mol Biol, Beijing 100730, Peoples R China.
[Rao, Dabeeru C.; Rice, Treva K.; Gu, Charles] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA.
[Mu, Jianjun] Xi An Jiao Tong Univ, Dept Med, Xian, Shanxi, Peoples R China.
[Ma, Jixiang] Shandong Ctr Dis Control & Prevent, Shandong, Peoples R China.
[Jaquish, Cashell E.] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA.
[Whelton, Paul K.] Loyola Univ Hlth Syst, Off President, Maywood, IL USA.
[Whelton, Paul K.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA.
RP Kelly, TN (reprint author), Tulane Univ, Dept Epidemiol, Sch Publ Hlth & Trop Med, 1440 Canal St,Suite 2000, New Orleans, LA 70112 USA.
EM tkelly@tulane.edu
RI Gu, Charles/A-7934-2010
OI Gu, Charles/0000-0002-8527-8145
FU National Heart, Lung, and Blood Institute, National Institutes of
Health, Bethesda, Maryland, USA [U01HL072507, R01HL087263, R01HL090682]
FX The GenSalt is supported by research grants (U01HL072507, R01HL087263,
and R01HL090682) from the National Heart, Lung, and Blood Institute,
National Institutes of Health, Bethesda, Maryland, USA.
NR 42
TC 25
Z9 27
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0263-6352
J9 J HYPERTENS
JI J. Hypertens.
PD JUN
PY 2010
VL 28
IS 6
BP 1210
EP 1220
DI 10.1097/HJH.0b013e3283383655
PG 11
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 595PG
UT WOS:000277623500015
PM 20486282
ER
PT J
AU Ben-Shlomo, Y
McEniery, C
Boutouyrie, P
Cameron, J
Chen, CH
Cruickshank, K
Lakatta, E
Laurent, S
Maldonado, J
Newman, A
Ohishi, M
Pannier, B
Pereira, T
Shokawa, T
Sutton-Tyrell, K
Webb, D
Wilkinson, I
Hansen, TW
Zoungas, S
Cockcroft, J
AF Ben-Shlomo, Y.
McEniery, C.
Boutouyrie, P.
Cameron, J.
Chen, C. H.
Cruickshank, K.
Lakatta, E.
Laurent, S.
Maldonado, J.
Newman, A.
Ohishi, M.
Pannier, B.
Pereira, T.
Shokawa, T.
Sutton-Tyrell, K.
Webb, D.
Wilkinson, I.
Hansen, T. Willum
Zoungas, S.
Cockcroft, J.
TI PREDICTIVE VALUE OF PULSE WAVE VELOCITY FOR CARDIOVASCULAR EVENTS IN
15220 SUBJECTS: AN INDIVIDUAL PARTICIPANT META-ANALYSIS ON BEHALF OF THE
PWV COLLABORATIVE GROUP
SO JOURNAL OF HYPERTENSION
LA English
DT Meeting Abstract
CT 20th Annual Meeting of the European-Society-of-Hypertension
CY JUN 18-21, 2010
CL Oslo, NORWAY
SP European Soc Hypertens
C1 [Ben-Shlomo, Y.] Univ Bristol, Dept Social Med, Bristol, Avon, England.
[McEniery, C.; Wilkinson, I.] Addenbrookes Hosp, Clin Pharmacol Unit, Cambridge CB2 2QQ, England.
[Boutouyrie, P.; Laurent, S.] INSERM, Paris, France.
[Cameron, J.] Monash Univ, Dept Vasc Sci, Victoria, BC, Canada.
[Chen, C. H.] Yang Ming Univ, Dept Med, Taipei, Taiwan.
[Cruickshank, K.] Univ Manchester, Manchester, Lancs, England.
[Lakatta, E.] NIH, Cardiovasc Sci Lab, Baltimore, MD USA.
[Maldonado, J.] Inst Invest & Formacao Cardiovasc, Penacova, Portugal.
[Newman, A.; Sutton-Tyrell, K.] Ctr Aging & Populat Hlth, Pittsburgh, PA USA.
[Ohishi, M.] Osaka Univ, Sch Med, Dept Geriatr Med, Osaka 553, Japan.
[Pannier, B.] Ctr Invest Prevent & Clin, Paris, France.
[Pereira, T.] Escola Super Tecnol Saude Coimbra, Coimbra, Portugal.
[Shokawa, T.] Hiroshima Univ, Dept Cardiovasc Med, Grad Sch Biomed Sci, Hiroshima, Japan.
[Webb, D.] Clin Pharmacol Unit, Edinburgh, Midlothian, Scotland.
[Hansen, T. Willum] Res Ctr Prevent & Healt, Copenhagen, Denmark.
[Cockcroft, J.] Wales Heart Res Inst, Cardiff, S Glam, Wales.
RI Boutouyrie, Pierre/J-8592-2015; Laurent, Stephane/J-8624-2015
OI Boutouyrie, Pierre/0000-0002-4375-3569;
NR 0
TC 6
Z9 6
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0263-6352
J9 J HYPERTENS
JI J. Hypertens.
PD JUN
PY 2010
VL 28
SU A
BP E446
EP E446
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 665GM
UT WOS:000283023404235
ER
PT J
AU Emelyanov, I
Ivanenko, V
Frolova, E
Konrady, A
Bagrov, A
AF Emelyanov, I.
Ivanenko, V.
Frolova, E.
Konrady, A.
Bagrov, A.
TI MARINOBUFAGENIN-INDUCED SODIUM PUMP INHIBITION ASSOCIATES WITH PRESSOR
RESPONSE TO MILD SALT LOADING IN PATIENTS WITH RESISTANT HYPERTENSION
SO JOURNAL OF HYPERTENSION
LA English
DT Meeting Abstract
CT 20th Annual Meeting of the European-Society-of-Hypertension
CY JUN 18-21, 2010
CL Oslo, NORWAY
SP European Soc Hypertens
C1 [Emelyanov, I.; Ivanenko, V.; Konrady, A.] Almazov Fed Ctr Heart Blood & Endocrinol, St Petersburg, Russia.
[Frolova, E.] IM Sechenov Evolutionary Physiol & Biochem Inst, St Petersburg 194223, Russia.
[Bagrov, A.] NIA, NIH, Baltimore, MD 21224 USA.
RI Konradi, Alexandra/P-1547-2014
OI Konradi, Alexandra/0000-0001-8169-7812
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0263-6352
J9 J HYPERTENS
JI J. Hypertens.
PD JUN
PY 2010
VL 28
SU A
BP E211
EP E211
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 665GM
UT WOS:000283023403048
ER
PT J
AU Fernandez-Llama, P
Khositseth, S
Gonzales, PA
Star, RA
Pisitkun, T
Knepper, MA
AF Fernandez-Llama, P.
Khositseth, S.
Gonzales, P. A.
Star, R. A.
Pisitkun, T.
Knepper, M. A.
TI TAMM-HORSFALL PROTEIN AND URINARY EXOSOME ISOLATION
SO JOURNAL OF HYPERTENSION
LA English
DT Meeting Abstract
CT 20th Annual Meeting of the European-Society-of-Hypertension
CY JUN 18-21, 2010
CL Oslo, NORWAY
SP European Soc Hypertens
C1 [Fernandez-Llama, P.] Renal Unit, Barcelona, Spain.
[Khositseth, S.; Gonzales, P. A.; Pisitkun, T.; Knepper, M. A.] NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA.
[Star, R. A.] NIDDK, Renal Diagnost & Therapeut Unit, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0263-6352
J9 J HYPERTENS
JI J. Hypertens.
PD JUN
PY 2010
VL 28
SU A
BP E164
EP E164
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 665GM
UT WOS:000283023402384
ER
PT J
AU Lee, JH
Goldstein, MS
Brown, ER
Ballard-Barbash, R
AF Lee, Jennifer H.
Goldstein, Michael S.
Brown, E. Richard
Ballard-Barbash, Rachel
TI How Does Acculturation Affect the Use of Complementary and Alternative
Medicine Providers Among Mexican- and Asian- Americans?
SO JOURNAL OF IMMIGRANT AND MINORITY HEALTH
LA English
DT Article
DE Acculturation; Complementary and alternative medicine providers; Mexican
American; Asian American
ID UNITED-STATES; KOREAN-AMERICANS; HEALTH; ASSIMILATION; POPULATIONS;
PREVALENCE; CARE; CAM
AB Researchers have found that immigrants in the United States gradually relinquish cultural practices and adopt health behaviors similar to native born individuals as they acculturate. Few studies have looked at acculturation and Complementary and Alternative Medicine (CAM) use, particularly ethnic forms of CAM. This study uses data from the 2001 California Health Interview Survey-Complementary and Alternative Medicine (CHIS-CAM) supplement to estimate the prevalence of CAM provider use among Mexican- and Asian- Americans and examine the relationship of acculturation on use. Multinomial logistic regression models were used to predict the probability of provider use based on socio-demographic variables, health status and acculturation. Mexican- and Asian- Americans who have spent more time in the US were more likely to use chiropractors or massage therapists compared to no CAM provider. Both groups were less likely to use ethnic-specific CAM providers with more time in the US compared to chiropractors or massage therapists.
C1 [Lee, Jennifer H.; Brown, E. Richard] Univ Calif Los Angeles, UCLA Ctr Hlth Policy Res, Los Angeles, CA 90024 USA.
[Lee, Jennifer H.; Goldstein, Michael S.] Univ Calif Los Angeles, Dept Community Hlth Sci, Sch Publ Hlth, Los Angeles, CA 90024 USA.
[Ballard-Barbash, Rachel] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Lee, JH (reprint author), Univ Calif Los Angeles, UCLA Ctr Hlth Policy Res, 10960 Wilshire Blvd,Suite 1550, Los Angeles, CA 90024 USA.
EM jen.lee@ucla.edu
FU NCI NIH HHS [N02-PC-95057]
NR 27
TC 10
Z9 10
U1 1
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1557-1912
J9 J IMMIGR MINOR HEALT
JI J. Immigr. Minor. Health
PD JUN
PY 2010
VL 12
IS 3
BP 302
EP 309
DI 10.1007/s10903-008-9171-1
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 645ZW
UT WOS:000281505700004
PM 18677650
ER
PT J
AU Frankel, TL
Burns, WR
Peng, PD
Yu, ZY
Chinnasamy, D
Wargo, JA
Zheng, ZL
Restifo, NP
Rosenberg, SA
Morgan, RA
AF Frankel, Timothy L.
Burns, William R.
Peng, Peter D.
Yu, Zhiya
Chinnasamy, Dhanalakshmi
Wargo, Jennifer A.
Zheng, Zhili
Restifo, Nicholas P.
Rosenberg, Steven A.
Morgan, Richard A.
TI Both CD4 and CD8 T Cells Mediate Equally Effective In Vivo Tumor
Treatment When Engineered with a Highly Avid TCR Targeting Tyrosinase
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID METASTATIC MELANOMA; INFILTRATING LYMPHOCYTES; CANCER REGRESSION;
HETEROGENEOUS EXPRESSION; ESTABLISHED MELANOMA; VACCINE DEVELOPMENT;
ANTIGEN EXPRESSION; PERIPHERAL-BLOOD; GENE-THERAPY; IMMUNOTHERAPY
AB Tyrosinase, an enzyme involved in melanin synthesis, is expressed in nearly all primary and metastatic melanoma lesions and thus is an attractive target for TCR-based gene therapy using adoptive cell transfer. The TCR alpha- and beta-chain genes from a tumor-infiltrating lymphocyte, which recognized the tyrosinase 368-376 peptide in the context of HLA-A2, were cloned into a gamma-retroviral vector. Following transduction of PBL, specific reactivity was confirmed by cytokine production following coculture with tumor targets. Experiments using Ab blockade and CD4/CD8 sorting of the transduced PBLs demonstrated that this antityrosinase TCR was CD4/CD8 independent. The introduction of a second disulfide bond between the TCR constant regions and/or creation of a chimeric protein in which the human constant regions were replaced by murine homologs resulted in enhanced TCR expression as demonstrated by tetramer staining and improved tumor reactivity that was comparable to PBL transduced with either anti-melanoma Ag recognized by T cells-1 or anti-gp100 TCR vectors currently used in clinical trials. The chimeric TCR also allowed us to test antitumor function of in HLA-A2/K(b)-transgenic mice. Transfer of the antityrosinase TCR into mouse splenocytes conferred CD4/CD8-independent, HLA-A2-restricted Ag reactivity against B16/A2K(b) murine melanoma in vitro. Furthermore, adoptive transfer of transduced splenocytes mediated B16/A2K(b) melanoma tumor regression in lymphodepleted mice, and, surprisingly, both CD8 and CD4 T cells were equally effective in mediating tumor regression. These results suggest that this highly active tyrosinase-specific TCR could be of value in adoptive cell transfer for melanoma. The Journal of Immunology, 2010, 184: 5988-5998.
C1 [Frankel, Timothy L.; Burns, William R.; Peng, Peter D.; Yu, Zhiya; Chinnasamy, Dhanalakshmi; Wargo, Jennifer A.; Zheng, Zhili; Restifo, Nicholas P.; Rosenberg, Steven A.; Morgan, Richard A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
RP Morgan, RA (reprint author), 10 Ctr Dr,Bldg 10,Room 3-5940, Bethesda, MD 20892 USA.
EM rmorgan@mail.nih.gov
RI Restifo, Nicholas/A-5713-2008;
OI Restifo, Nicholas P./0000-0003-4229-4580
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health
FX This work was supported by the Intramural Research Program of the Center
for Cancer Research, National Cancer Institute, National Institutes of
Health.
NR 48
TC 42
Z9 42
U1 1
U2 7
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUN 1
PY 2010
VL 184
IS 11
BP 5988
EP 5998
DI 10.4049/jimmunol.1000189
PG 11
WC Immunology
SC Immunology
GA 606PP
UT WOS:000278439600010
PM 20427771
ER
PT J
AU Fang, F
Wang, Y
Li, R
Zhao, Y
Guo, Y
Jiang, M
Sun, J
Ma, Y
Ren, ZJ
Tian, ZG
Wei, F
Yang, D
Xiao, WH
AF Fang, Fang
Wang, Yan
Li, Rui
Zhao, Ying
Guo, Yang
Jiang, Ming
Sun, Jie
Ma, Yang
Ren, Zijia
Tian, Zhigang
Wei, Feng
Yang, De
Xiao, Weihua
TI Transcription Factor E2F1 Suppresses Dendritic Cell Maturation
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID NF-KAPPA-B; SIGNAL-TRANSDUCTION PATHWAYS; ACTIVATED PROTEIN-KINASE;
IMMUNE-RESPONSES; TNF-ALPHA; PROLIFERATION; APOPTOSIS; EXPRESSION;
LIPOPOLYSACCHARIDE; INDUCTION
AB Transcription factor E2F1 has been largely studied as a promoter of S-phase transition in the cell cycle and as a regulator of apoptosis. Recently, E2F1 has been shown to regulate a wide range of genes in response to inflammatory stimulation of macrophages and to contribute to T cell activation in response to pathogens, implicating an extensive immunological role for E2F1. Dendritic cells (DCs) play critical roles as professional APCs in the development of immune responses. However, it is unclear whether E2F1 has any effect on DC phenotype or function. In this paper, we report that E2F1 acts as a suppressor of DC maturation. The level of E2F1 expression was transiently downregulated in the course of LPS-induced maturation of both human monocyte-derived DCs and a mouse DC cell line, DC2.4. Knockdown of E2F1 by small interfering RNA in DC2.4 cells resulted in both phenotypic and functional maturation, even without LPS treatment. Conversely, ectopic overexpression of E2F1 suppressed LPS-induced maturation of DC2.4 cells. Furthermore, knockdown of E2F1 caused the activation of several major signaling pathways known to be activated in the course of DC maturation, including Erk1/2, NF-kappa B, and PI3K/Akt, suggesting that E2F1 may be involved in regulating multiple signaling pathways in DCs. Finally, the alteration of phenotypic maturation by E2F1 was confirmed with bone marrow-derived DCs from E2F1 knockout mice. Overall, our data demonstrate for the first time that E2F1 is a critical regulator of DC maturation. The Journal of Immunology, 2010, 184: 6084-6091.
C1 [Xiao, Weihua] Univ Sci & Technol China, Inst Immunol, Sch Life Sci, Hefei 230027, Peoples R China.
[Fang, Fang; Wang, Yan; Li, Rui; Zhao, Ying; Guo, Yang; Jiang, Ming; Sun, Jie; Ma, Yang; Ren, Zijia; Tian, Zhigang; Xiao, Weihua] Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Peoples R China.
[Wei, Feng; Yang, De] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA.
[Yang, De] NCI, Basic Sci Program, Sci Applicat Int Corp Frederick, Frederick, MD 21702 USA.
RP Xiao, WH (reprint author), Univ Sci & Technol China, Inst Immunol, Sch Life Sci, 443 Huangshan Rd, Hefei 230027, Peoples R China.
EM yangd@mail.nih.gov; xiaow@ustc.edu.cn
RI Xiao, Weihua/N-2775-2013; Tian, Zhigang/J-3512-2013
OI Xiao, Weihua/0000-0001-9102-6326;
FU National Natural Science Foundation of China [30721002, 30528020];
National Basic Research Program of China (973 Program) [2007CB914503];
Ministry of Science and Technology of China [KSCX1-YW-R-58,
KSCX2-YW-R-174]; China Ministry of Education [20060358019]; National
Cancer Institute, National Institutes of Health [N01-CO-12400]; National
Institutes of Health, National Cancer Institute, Center for Cancer
Research
FX This work was supported by grants from the National Natural Science
Foundation of China (30721002 and 30528020), National Basic Research
Program of China (973 Program) (2007CB914503), Ministry of Science and
Technology of China (KSCX1-YW-R-58 and KSCX2-YW-R-174), and China
Ministry of Education (20060358019). Funding to pay the open access
publication charges for this article was provided by a grant from the
National Basic Research Program of China (2007CB914503; to W. X.). This
research has been funded in whole or in part with federal funds from the
National Cancer Institute, National Institutes of Health, under Contract
N01-CO-12400. This research was supported in part by the Intramural
Research Program of the National Institutes of Health, National Cancer
Institute, Center for Cancer Research.
NR 40
TC 16
Z9 17
U1 0
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 JUN 1
PY 2010
VL 184
IS 11
BP 6084
EP 6091
DI 10.4049/jimmunol.0902561
PG 8
WC Immunology
SC Immunology
GA 606PP
UT WOS:000278439600021
PM 20421650
ER
PT J
AU Bialer, G
Horovitz-Fried, M
Ya'acobi, S
Morgan, RA
Cohen, CJ
AF Bialer, Gil
Horovitz-Fried, Miryam
Ya'acobi, Shlomo
Morgan, Richard A.
Cohen, Cyrille J.
TI Selected Murine Residues Endow Human TCR with Enhanced Tumor Recognition
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID T-CELL-RECEPTOR; CANCER REGRESSION; LYMPHOCYTES; THERAPY; ANTIGEN;
MELANOMA; AVIDITY; COMPLEX; SINGLE
AB TCR-gene transfer can mediate tumor regression in terminally ill melanoma patients. However, the formation of mix dimers between endogenous and transduced TCR chains may result in the surface dilution of the introduced TCR, which translates in poorer cellular avidity. Recently, we reported that murinization of human TCRs (i.e., the replacement of human C regions by murine ones) can improve TCR function. However, because xenogenic sequences may trigger immunogenicity, we sought to identify the essential murine residues that mediate this enhanced functional effect. We constructed murine/human chimeras of alpha- and beta-chains and assessed for their surface expression and function. We identified an evolutionary-unique lysine residue in C beta, central to murine TCR function. The mapping of C alpha revealed that a few short stretches of amino acids play a role in enhancing TCR function, one of the most important ones being the SDVP sequence. This information led us to design improved and minimally murinized human TCR C regions that mediate increased tumor recognition. This also enabled us to suggest a structural model that could explain the role of the aforementioned residues in promoting the preferential pairing and stability of murinized TCRs. Overall, these findings could have implications for the treatment of malignant diseases using TCR-gene transfer. The Journal of Immunology, 2010, 184: 6232-6241.
C1 [Bialer, Gil; Horovitz-Fried, Miryam; Ya'acobi, Shlomo; Cohen, Cyrille J.] Bar Ilan Univ, Lab Tumor Immunol & Immunotherapy, Mina & Everard Goodman Fac Life Sci, IL-52900 Ramat Gan, Israel.
[Morgan, Richard A.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Cohen, CJ (reprint author), Bar Ilan Univ, Lab Tumor Immunol & Immunotherapy, Mina & Everard Goodman Fac Life Sci, Gonda Bldg 204,Room 105, IL-52900 Ramat Gan, Israel.
EM cohency@mail.biu.ac.il
FU Israel Science Foundation [773/08, 1702/08]; Council of Higher
Education, Israel; European Community [224851]; Milstein Foundation
FX This work was supported in part by a research grant (773/08) and an
equipment grant (1702/08) from the Israel Science Foundation. C.J.C. was
supported by the Alon Fellowship for outstanding young investigators
(the Council of Higher Education, Israel) and by a Marie-Curie
International Reintegration grant (224851) from the European Community.
The flow cytometer apparatus was financed thanks to the generous support
of the Milstein Foundation.
NR 23
TC 39
Z9 42
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUN 1
PY 2010
VL 184
IS 11
BP 6232
EP 6241
DI 10.4049/jimmunol.0902047
PG 10
WC Immunology
SC Immunology
GA 606PP
UT WOS:000278439600036
PM 20427762
ER
PT J
AU Dyer, KD
Percopo, CM
Xie, ZH
Yang, Z
Kim, JD
Davoine, F
Lacy, P
Druey, KM
Moqbel, R
Rosenberg, HF
AF Dyer, Kimberly D.
Percopo, Caroline M.
Xie, Zhihui
Yang, Zhao
Kim, John Dongil
Davoine, Francis
Lacy, Paige
Druey, Kirk M.
Moqbel, Redwan
Rosenberg, Helene F.
TI Mouse and Human Eosinophils Degranulate in Response to
Platelet-Activating Factor (PAF) and LysoPAF via a
PAF-Receptor-Independent Mechanism: Evidence for a Novel Receptor
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID PROTEIN-KINASE-C; AIRWAY INFLAMMATION; FACTOR ANTAGONISTS; PREFORMED
IL-4; ASTHMA MODEL; GUINEA-PIG; RELEASE; MICE; ANAPHYLAXIS;
ACETYLHYDROLASE
AB Platelet-activating factor (PAF [1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine]) is a phospholipid mediator released from activated macrophages, mast cells, and basophils that promotes pathophysiologic inflammation. Eosinophil responses to PAF are complex and incompletely elucidated. We show in this article that PAF and its 2-deacetylated metabolite (lysoPAF) promote degranulation (release of eosinophil peroxidase) via a mechanism that is independent of the characterized PAFR. Specifically, we demonstrate that receptor antagonists CV-3988 and WEB-2086 and pertussis toxin have no impact on PAF- or lysoPAF-mediated degranulation. Furthermore, cultured mouse eosinophils from PAFR(-/-) bone marrow progenitors degranulate in response to PAF and lysoPAF in a manner indistinguishable from their wild-type counterparts. In addition to PAF and lysoPAF, human eosinophils degranulate in response to lysophosphatidylcholine, but not phosphatidylcholine, lysophosphatidylethanolamine, or phosphatidylethanolamine, demonstrating selective responses to phospholipids with a choline head-group and minimal substitution at the sn-2 hydroxyl. Human eosinophils release preformed cytokines in response to PAF, but not lysoPAF, also via a PAFR-independent mechanism. Mouse eosinophils do not release cytokines in response to PAF or lysoPAF, but they are capable of doing so in response to IL-6. Overall, our work provides the first direct evidence for a role for PAF in activating and inducing degranulation of mouse eosinophils, a crucial feature for the interpretation of mouse models of PAF-mediated asthma and anaphylaxis. Likewise, we document and define PAF and lysoPAF-mediated activities that are not dependent on signaling via PAFR, suggesting the existence of other unexplored molecular signaling pathways mediating responses from PAF, lysoPAF, and closely related phospholipid mediators. The Journal of Immunology, 2010, 184: 6327-6334.
C1 [Dyer, Kimberly D.; Percopo, Caroline M.; Rosenberg, Helene F.] NIAID, Sect Eosinophil Biol, NIH, Bethesda, MD 20892 USA.
[Xie, Zhihui; Yang, Zhao; Druey, Kirk M.] NIAID, Sect Mol Signal Transduct, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Kim, John Dongil; Davoine, Francis; Lacy, Paige; Moqbel, Redwan] Univ Alberta, Dept Med, Pulm Res Grp, Edmonton, AB, Canada.
[Moqbel, Redwan] Univ Manitoba, Fac Med, Dept Immunol, Winnipeg, MB R3E 0W3, Canada.
RP Dyer, KD (reprint author), NIAID, Sect Eosinophil Biol, NIH, Bldg 10,Room 11C216,10 Ctr Dr, Bethesda, MD 20892 USA.
EM kdyer@niaid.nih.gov
OI Lacy, Paige/0000-0001-8885-6011
FU Eosinophil Biology Section from the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases [AI00941-06]
FX This work was supported by funding from the Eosinophil Biology Section
from the Division of Intramural Research, National Institute of Allergy
and Infectious Diseases (AI00941-06) to H. F. R.
NR 55
TC 40
Z9 40
U1 0
U2 2
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUN 1
PY 2010
VL 184
IS 11
BP 6327
EP 6334
DI 10.4049/jimmunol.0904043
PG 8
WC Immunology
SC Immunology
GA 606PP
UT WOS:000278439600047
PM 20421642
ER
PT J
AU Lee, DC
Romero, R
Kim, CJ
Chaiworapongsa, T
Tarca, AL
Lee, J
Suh, YL
Mazaki-Tovi, S
Vaisbuch, E
Mittal, P
Draghici, S
Erez, O
Kusanovic, JP
Hassan, SS
Kim, JS
AF Lee, Deug-Chan
Romero, Roberto
Kim, Chong Jai
Chaiworapongsa, Tinnakorn
Tarca, Adi L.
Lee, JoonHo
Suh, Yeon-Lim
Mazaki-Tovi, Shali
Vaisbuch, Edi
Mittal, Pooja
Draghici, Sorin
Erez, Offer
Kusanovic, Juan Pedro
Hassan, Sonia S.
Kim, Jung-Sun
TI Surfactant Protein-A as an Anti-Inflammatory Component in the Amnion:
Implications for Human Pregnancy
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID NEURAL-TUBE DEFECTS; SPONTANEOUS LABOR; FETAL MEMBRANES; HUMAN
PARTURITION; HUMAN-PLACENTA; LAVAGE FLUID; SP-A2 GENES; IN-VIVO;
EXPRESSION; LUNG
AB The mechanism of mouse parturition is thought to involve myometrial infiltration by amniotic fluid (AF) macrophages, activated by surfactant protein-A (SP-A). In humans, the concentration of AF SP-A decreases during labor, and no fetal macrophages are found in the myometrium after labor. Therefore, it appears that the mechanisms of labor in mice and humans are different. We investigated a potential role for SP-A in human pregnancy and parturition by examining SP-A expression patterns in AF and amnion. High molecular mass (>250 kDa) oligomeric SP-A was increased in AF with advancing gestation. Interestingly, these oligomers were more abundant in placental amnion before labor at term, while they increased primarily in reflected amnion during labor (p < 0.05). Immunoblotting showed a binding of high molecular mass SP-A in AF to amnion. In C57BL/6 mice, oligomeric SP-A was also readily detected in AF from E15 onwards, but not in amnion. Macrophage density in mice myometrium did not change with advancing gestational age. Microarray analysis of human amnion explants incubated with SP-A revealed a molecular signature of inhibited cytokine-cytokine receptor interaction with downregulation of IL-1 beta, CXCL2, and CXCL5 mRNA expression. The findings in this study strongly suggest that SP-A signals amniotic anti-inflammatory response via AF during pregnancy. We propose that an SP-A interaction among AF, placental amnion, and reflected amnion is a unique mechanism for immunoregulation in human pregnancy akin to that established in lung biology. However, AF SP-A and fetal macrophages by themselves do not seem to be exclusive effectors of parturition in humans. The Journal of Immunology, 2010, 184: 6479-6491.
C1 [Lee, Deug-Chan; Romero, Roberto; Kim, Chong Jai; Chaiworapongsa, Tinnakorn; Tarca, Adi L.; Lee, JoonHo; Mazaki-Tovi, Shali; Vaisbuch, Edi; Mittal, Pooja; Erez, Offer; Kusanovic, Juan Pedro; Hassan, Sonia S.; Kim, Jung-Sun] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
[Romero, Roberto; Chaiworapongsa, Tinnakorn; Mazaki-Tovi, Shali; Vaisbuch, Edi; Mittal, Pooja; Erez, Offer; Kusanovic, Juan Pedro; Hassan, Sonia S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Romero, Roberto; Tarca, Adi L.] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA.
[Kim, Chong Jai; Kim, Jung-Sun] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA.
[Tarca, Adi L.; Draghici, Sorin] Wayne State Univ, Sch Med, Dept Comp Sci, Detroit, MI 48201 USA.
[Suh, Yeon-Lim; Kim, Jung-Sun] Sungkyunkwan Univ, Sch Med, Dept Pathol, Seoul, South Korea.
RP Kim, JS (reprint author), Wayne State Univ, Sch Med, Hutzel Womens Hosp, Dept Pathol, 3990 John R,4 Brush N,Room 4606, Detroit, MI 48201 USA.
EM jkim@med.wayne.edu
RI Draghici, Sorin/B-3074-2013;
OI Draghici, Sorin/0000-0002-0786-8377; Vaisbuch, Edi/0000-0002-8400-9031
FU Perinatology Research Branch, Division of Intramural Research,
Department of Health and Human Services, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health
FX This work was supported by the Perinatology Research Branch, Division of
Intramural Research, Department of Health and Human Services, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health.
NR 54
TC 19
Z9 20
U1 0
U2 9
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUN 1
PY 2010
VL 184
IS 11
BP 6479
EP 6491
DI 10.4049/jimmunol.0903867
PG 13
WC Immunology
SC Immunology
GA 606PP
UT WOS:000278439600063
PM 20439915
ER
PT J
AU Prieto, PA
Durflinger, KH
Wunderlich, JR
Rosenberg, SA
Dudley, ME
AF Prieto, Peter A.
Durflinger, Katherine H.
Wunderlich, John R.
Rosenberg, Steven A.
Dudley, Mark E.
TI Enrichment of CD8(+) Cells From Melanoma Tumor-infiltrating Lymphocyte
Cultures Reveals Tumor Reactivity for Use in Adoptive Cell Therapy
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE tumor-infiltrating lymphocytes (TIL); minimally cultured lymphocytes
(young TIL); immunotherapy; CD8(+) enrichment; CliniMACS
ID REGULATORY T-CELLS; BLOOD MONONUCLEAR-CELLS; METASTATIC MELANOMA; CANCER
REGRESSION; PHASE-I; ANTIGEN; CHEMOTHERAPY; TRANSPLANTATION;
INTERLEUKIN-2; AUTOIMMUNITY
AB Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) for metastatic melanoma has shown objective response rates as high as 72%. The successful application of this therapy requires the selection of unique tumor-reactive lymphocyte cultures for each patient. This is a technically and logistically difficult undertaking, and patients who do not have tumor-reactive TIL are not considered eligible for treatment. To simplify the methods of TIL generation and extend TIL-based immunotherapy to additional patients, methods were developed to use unselected, minimally cultured ("young") TIL. Young TIL cultures contain a variable number of CD8(+), CD4(+), and CD3(-)CD56(+) natural killer cells. In this study we retrospectively investigated a role for these subsets in the clinical outcome of patients treated with TIL derived from selected microcultures. This analysis demonstrated a suggestive but nonsignificant association between the number of CD8(+) cells administered and tumor regression. We therefore investigated the feasibility of selecting CD8+ cells from young TIL cultures for ACT therapy. The available methods for clinical scale CD8(+) enrichment proved inadequate for TIL, so an optimized CD8(+) enrichment method was developed and is reported here. We observed that CD8(+) enrichment of some TIL cultures revealed in vitro tumor recognition that was not evident in bulk culture, and an improved in vitro recognition of tumor in other TIL cultures. In addition, the enriched CD8(+) young TIL expanded more reliably and predictably in rapid expansions than the bulk TIL. Thus, optimized CD8(+) selection combines the benefits of antigen-selected TIL and young TIL for generating lymphocyte cultures for ACT, and should be evaluated in cell transfer therapy protocols.
C1 [Prieto, Peter A.; Durflinger, Katherine H.; Wunderlich, John R.; Rosenberg, Steven A.; Dudley, Mark E.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
RP Prieto, PA (reprint author), NCI, Surg Branch, NIH, CRC 3W-5809,10 Ctr Dr, Bethesda, MD 20892 USA.
EM prietop@mail.nih.gov
NR 38
TC 38
Z9 39
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD JUN
PY 2010
VL 33
IS 5
BP 547
EP 556
PG 10
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 601YQ
UT WOS:000278104600012
PM 20463593
ER
PT J
AU Ison, MG
de Jong, MD
Gilligan, KJ
Higgs, ES
Pavia, AT
Pierson, J
Hayden, FG
AF Ison, Michael G.
de Jong, Menno D.
Gilligan, Kevin J.
Higgs, Elizabeth S.
Pavia, Andrew T.
Pierson, Jerome
Hayden, Frederick G.
TI End Points for Testing Influenza Antiviral Treatments for Patients at
High Risk of Severe and Life-Threatening Disease
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID A H1N1 VIRUS; CELL TRANSPLANT RECIPIENTS; NEURAMINIDASE INHIBITOR
OSELTAMIVIR; HOSPITALIZED-PATIENTS; UNITED-STATES; IMMUNOCOMPROMISED
PATIENT; ADAMANTANE RESISTANCE; CONTROLLED-TRIAL; CASE SERIES; INFECTION
AB Influenza infection results in substantial morbidity and mortality in hospitalized patients, including those who are immuno-compromised or pregnant. Antiviral therapy likely provides considerable benefit to these patients, but few studies have been successfully conducted in these high-risk populations, and no drugs are specifically licensed for treating these subgroups. One of the key challenges facing novel antiviral drug development for influenza is determining the appropriate efficacy end points that would enable rapid regulatory approval for drug use in seriously ill patients, for whom risk-benefit assessments differ from those with uncomplicated illness. All available antiviral drugs currently affect viral replication, and respiratory tract viral titers correlate with both symptoms and measures of host inflammatory responses, including cytokine and chemokine expression that are likely responsible for many of the clinical symptoms. Consequently, we outline the evidence to support the use of primary virological end points in studies of antiviral agents involving patients who are hospitalized with severe influenza or those who are at high risk of severe and life-threatening disease.
C1 [Ison, Michael G.] Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60611 USA.
[Ison, Michael G.] Northwestern Univ, Feinberg Sch Med, Div Organ Transplantat, Chicago, IL 60611 USA.
[Gilligan, Kevin J.] US Dept HHS, Biomed Adv Res & Dev Author, Washington, DC 20201 USA.
[Higgs, Elizabeth S.; Pierson, Jerome] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA.
[Pavia, Andrew T.] Univ Utah, Div Pediat Infect Dis, Salt Lake City, UT USA.
[Hayden, Frederick G.] Univ Virginia, Sch Med, Dept Med, Div Infect Dis & Int Hlth, Charlottesville, VA 22908 USA.
[de Jong, Menno D.] Univ Amsterdam, Acad Med Ctr, Dept Med Microbiol, NL-1105 AZ Amsterdam, Netherlands.
[Hayden, Frederick G.] Wellcome Trust Res Labs, Int Act, London, England.
RP Ison, MG (reprint author), Northwestern Univ, Feinberg Sch Med, Div Infect Dis, 645 N Michigan Ave,Ste 900, Chicago, IL 60611 USA.
EM mgison@northwestern.edu
FU Roche; BioCryst; Adamas; ADMA Biologics
FX Potential conflicts of interest: M. I.: Received research support (paid
to the University) from Roche, BioCryst, Adamas, and ADMA Biologics;
unpaid consultant for Biota and NexBio; paid speaker for Abbott
Molecular. A. P.: Consultant to NexBio. F. H.: Unpaid consultant to
multiple companies involved in influenza antiviral development
(including Roche, GlaxoSmithKline, BioCryst, Nexbio, Toyama).
NR 65
TC 37
Z9 37
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD JUN 1
PY 2010
VL 201
IS 11
BP 1654
EP 1662
DI 10.1086/652498
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 589TH
UT WOS:000277176200008
PM 20423224
ER
PT J
AU Asmuth, DM
Murphy, RL
Rosenkranz, SL
Lertora, JJL
Kottilil, S
Cramer, Y
Chan, ES
Schooley, RT
Rinaldo, CR
Thielman, N
Li, XD
Wahl, SM
Shore, J
Janik, J
Lempicki, RA
Simpson, Y
Pollard, RB
AF Asmuth, David M.
Murphy, Robert L.
Rosenkranz, Susan L.
Lertora, Juan J. L.
Kottilil, Shyam
Cramer, Yoninah
Chan, Ellen S.
Schooley, Robert T.
Rinaldo, Charles R.
Thielman, Nathan
Li, Xiao-Dong
Wahl, Sharon M.
Shore, Jessica
Janik, Jennifer
Lempicki, Richard A.
Simpson, Yaa
Pollard, Richard B.
CA AIDS Clinical Trials Grp A5192 Tea
TI Safety, Tolerability, and Mechanisms of Antiretroviral Activity of
Pegylated Interferon Alfa-2a in HIV-1-Monoinfected Participants: A Phase
II Clinical Trial
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID CHRONIC HEPATITIS-C; IMMUNE-DEFICIENCY-SYNDROME; KAPOSIS-SARCOMA;
IFN-ALPHA; PEGINTERFERON ALPHA-2A; HIV-1 INFECTION; PLUS RIBAVIRIN;
COMBINATION THERAPY; REPLICATION CYCLE; VIRAL-INFECTIONS
AB Background. To our knowledge, the antiviral activity of pegylated interferon alfa-2a has not been studied in participants with untreated human immunodeficiency virus type 1 (HIV-1) infection but without chronic hepatitis C virus (HCV) infection.
Methods. Untreated HIV-1-infected volunteers without HCV infection received 180 mu g of pegylated interferon alfa-2a weekly for 12 weeks. Changes in plasma HIV-1 RNA load, CD4(+) T cell counts, pharmacokinetics, pharmacodynamic measurements of 2',5'-oligoadenylate synthetase (OAS) activity, and induction levels of interferoninducible genes (IFIGs) were measured. Nonparametric statistical analysis was performed.
Results. Eleven participants completed 12 weeks of therapy. The median plasma viral load decrease and change in CD4(+) T cell counts at week 12 were 0.61 log(10) copies/mL (90% confidence interval [CI], 0.20-1.18 log(10) copies/mL) and -44 cells/mu L (90% CI, -95 to 85 cells/mu L), respectively. There was no correlation between plasma viral load decreases and concurrent pegylated interferon plasma concentrations. However, participants with larger increases in OAS level exhibited greater decreases in plasma viral load at weeks 1 and 2 (r = -0.75 [90% CI, -0.93 to -0.28] and r = -0.61 [90% CI, -0.87 to -0.09], respectively; estimated Spearman rank correlation). Participants with higher baseline IFIG levels had smaller week 12 decreases in plasma viral load (0.66 log(10) copies/mL [90% CI, 0.06-0.91 log(10) copies/mL]), whereas those with larger IFIG induction levels exhibited larger decreases in plasma viral load (-0.74 log(10) copies/mL [90% CI, -0.93 to -0.21 log(10) copies/mL]).
Conclusion. Pegylated interferon alfa-2a was well tolerated and exhibited statistically significant anti-HIV-1 activity in HIV-1-monoinfected patients. The anti-HIV-1 effect correlated with OAS protein levels (weeks 1 and 2) and IFIG induction levels (week 12) but not with pegylated interferon concentrations.
C1 [Asmuth, David M.] Univ Calif Davis, Med Ctr, Div Infect Dis, Sacramento, CA 95817 USA.
[Schooley, Robert T.] Univ Calif San Diego, San Diego, CA 92103 USA.
[Murphy, Robert L.; Shore, Jessica; Simpson, Yaa] Northwestern Univ, Evanston, IL USA.
[Rosenkranz, Susan L.; Cramer, Yoninah; Chan, Ellen S.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Lertora, Juan J. L.; Kottilil, Shyam; Wahl, Sharon M.] Natl Inst Hlth Clin Ctr, Bethesda, MD USA.
[Lempicki, Richard A.] SAIC Frederick, Frederick, MD USA.
[Rinaldo, Charles R.] Univ Pittsburgh, Pittsburgh, PA USA.
[Thielman, Nathan] Duke Univ, Durham, NC USA.
[Janik, Jennifer] Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA.
RP Asmuth, DM (reprint author), Univ Calif Davis, Med Ctr, Div Infect Dis, 4150 V St,PSSB G500, Sacramento, CA 95817 USA.
EM david.asmuth@ucdmc.ucdavis.edu
RI Lempicki, Richard/E-1844-2012
OI Lempicki, Richard/0000-0002-7059-409X
FU Intramural NIH HHS; NIAID NIH HHS [1U01-AI069484, 1U01-AI068634,
1U01-AI068636, 1U01-AI069432, 1U01-AI069471, U01 AI068634, U01 AI068636,
U01 AI068636-01, U01 AI069432, U01 AI069471, U01 AI069484]
NR 41
TC 56
Z9 57
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD JUN 1
PY 2010
VL 201
IS 11
BP 1686
EP 1696
DI 10.1086/652420
PG 11
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 589TH
UT WOS:000277176200012
PM 20420510
ER
PT J
AU Arun, P
Madhavarao, CN
Moffett, JR
Hamilton, K
Grunberg, NE
Ariyannur, PS
Gahl, WA
Anikster, Y
Mog, S
Hallows, WC
Denu, JM
Namboodiri, AMA
AF Arun, Peethambaran
Madhavarao, Chikkathur N.
Moffett, John R.
Hamilton, Kristen
Grunberg, Neil E.
Ariyannur, Prasanth S.
Gahl, William A.
Anikster, Yair
Mog, Steven
Hallows, William C.
Denu, John M.
Namboodiri, Aryan M. A.
TI Metabolic acetate therapy improves phenotype in the tremor rat model of
Canavan disease
SO JOURNAL OF INHERITED METABOLIC DISEASE
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; N-ACETYLASPARTIC ACIDURIA; MYELIN
LIPID-SYNTHESIS; ACETYL-L-ASPARTATE; ASPARTOACYLASE GENE; SPONGY
DEGENERATION; BRAIN; MOUSE; CNS; DIFFERENTIATION
AB Genetic mutations that severely diminish the activity of aspartoacylase (ASPA) result in the fatal brain dysmyelinating disorder, Canavan disease. There is no effective treatment. ASPA produces free acetate from the concentrated brain metabolite, N-acetylaspartate (NAA). Because acetyl coenzyme A is a key building block for lipid synthesis, we postulated that the inability to catabolize NAA leads to a brain acetate deficiency during a critical period of CNS development, impairing myelination and possibly other aspects of brain development. We tested the hypothesis that acetate supplementation during postnatal myelination would ameliorate the severe phenotype associated with ASPA deficiency using the tremor rat model of Canavan disease. Glyceryltriacetate (GTA) was administered orally to tremor rats starting 7 days after birth, and was continued in food and water after weaning. Motor function, myelin lipids, and brain vacuolation were analyzed in GTA-treated and untreated tremor rats. Significant improvements were observed in motor performance and myelin galactocerebroside content in tremor rats treated with GTA. Further, brain vacuolation was modestly reduced, and these reductions were positively correlated with improved motor performance. We also examined the expression of the acetyl coenzyme A synthesizing enzyme acetyl coenzyme A synthase 1 and found upregulation of expression in tremor rats, with a return to near normal expression levels in GTA-treated tremor rats. These results confirm the critical role played by NAA-derived acetate in brain myelination and development, and demonstrate the potential usefulness of acetate therapy for the treatment of Canavan disease.
C1 [Arun, Peethambaran; Madhavarao, Chikkathur N.; Moffett, John R.; Ariyannur, Prasanth S.; Namboodiri, Aryan M. A.] Uniformed Serv Univ Hlth Sci, Mol & Cell Biol Program, Bethesda, MD 20814 USA.
[Hamilton, Kristen; Grunberg, Neil E.] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA.
[Gahl, William A.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Anikster, Yair] Chaim Sheba Med Ctr, Metab Dis Unit, Tel Aviv, Israel.
[Mog, Steven] Armed Forces Radiobiol Res Inst, Div Comparat Pathol, Bethesda, MD 20889 USA.
[Hallows, William C.; Denu, John M.] Univ Wisconsin, Dept Biomol Chem, Sch Med & Publ Hlth, Madison, WI 53706 USA.
[Arun, Peethambaran; Madhavarao, Chikkathur N.; Moffett, John R.; Ariyannur, Prasanth S.; Namboodiri, Aryan M. A.] Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Neurosci Program, Bethesda, MD 20814 USA.
RP Namboodiri, AMA (reprint author), Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Neurosci Program, Bldg C,4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM anamboodiri@usuhs.mil
RI Hamilton, Kristen/B-8116-2015;
OI Ariyannur, Prasanth/0000-0003-0888-8094
FU NINDS/NIH [NS39387]; Samueli Institute (Alexandria, VA); Jacob's Cure
(New York, NY); NTSAD (Boston, MA); American Academy of Neurology
Foundation; Canavan Foundation
FX This work was supported by grants from the NINDS/NIH (RO1/R56 grant
NS39387), the Samueli Institute (Alexandria, VA), Jacob's Cure (New
York, NY) and NTSAD (Boston, MA) to A.M.A.N. C.N.M. was supported by the
Rosalind Poss Rosen Clinical Research Training Fellowship of the
American Academy of Neurology Foundation co-sponsored by the Canavan
Foundation. We are grateful to the National Bio Resource Project for the
Rat in Japan (http://www.anim.med.kyoto-u.ac.jp/nbr/) for providing the
Tremor rat strain (NBRP-Rat#0015), and to Dr. James Garbern for
providing anti-ASPA antibodies.
NR 43
TC 32
Z9 32
U1 0
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0141-8955
J9 J INHERIT METAB DIS
JI J. Inherit. Metab. Dis.
PD JUN
PY 2010
VL 33
IS 3
BP 195
EP 210
DI 10.1007/s10545-010-9100-z
PG 16
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 602DV
UT WOS:000278119600001
PM 20464498
ER
PT J
AU Kim, J
Park, HS
Chang, PH
AF Kim, Jonghyun
Park, Hyung-Soon
Chang, Pyung Hun
TI Simple and Robust Attainment of Transparency Based on Two-Channel
Control Architectures Using Time-Delay Control
SO JOURNAL OF INTELLIGENT & ROBOTIC SYSTEMS
LA English
DT Article
DE Transparency; Two-channel control architecture; Time-delay control;
Bilateral teleoperation
ID BILATERAL TELEOPERATION; STABILITY ROBUSTNESS; SYSTEMS; ROBOT;
TELEMANIPULATION; MASTER; COMMUNICATION; TELEPRESENCE; MANIPULATORS;
FEEDBACK
AB This paper investigates simple and robust transparency-attainable control architectures for bilateral teleoperation. The strength of two-channel control architectures and time-delay control are exploited. First, two types of transparency-attainable two-channel control architecture are derived. In spite of the simplicity of using two communication channels, these architectures have problems in terms of implementation; they are not simple enough and not robust to uncertainties, such as errors in modeling the plant and force sensor noise. To solve the problems, time-delay control laws for two-channel control architecture are proposed. The model-independent, nonlinear, and robust characteristics of time-delay control mitigate the problems related to complexity and robustness. Finally, the proposed control laws are applied to experiments using a 2-DOF master-slave system. The experimental results confirm the validity of the theoretical approaches.
C1 [Kim, Jonghyun; Chang, Pyung Hun] Korea Adv Inst Sci & Technol, Dept Mech Engn, Taejon 305701, South Korea.
[Park, Hyung-Soon] NIH, Clin Res Ctr, Rehab Med Dept, Bethesda, MD 20892 USA.
RP Kim, J (reprint author), Korea Adv Inst Sci & Technol, Dept Mech Engn, 373-1 Guseong Dong, Taejon 305701, South Korea.
EM iskylark@mecha.kaist.ac.kr
RI Park, Hyung-Soon/B-3334-2010
OI Park, Hyung-Soon/0000-0003-4274-7420
NR 25
TC 2
Z9 2
U1 0
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0921-0296
J9 J INTELL ROBOT SYST
JI J. Intell. Robot. Syst.
PD JUN
PY 2010
VL 58
IS 3-4
BP 309
EP 337
DI 10.1007/s10846-009-9376-0
PG 29
WC Computer Science, Artificial Intelligence; Robotics
SC Computer Science; Robotics
GA 587VY
UT WOS:000277024200006
ER
PT J
AU Frank, AC
Zhang, XZ
Katsounas, A
Bharucha, JP
Kottilil, S
Imamichi, T
AF Frank, Astrid C.
Zhang, Xiaozhen
Katsounas, Antonios
Bharucha, Jennifer P.
Kottilil, Shyamasundaran
Imamichi, Tomozumi
TI Interleukin-27, an Anti-HIV-1 Cytokine, Inhibits Replication of
Hepatitis C Virus
SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD4(+) T-CELLS; ALPHA-2A PLUS RIBAVIRIN;
HIV-COINFECTED PERSONS; INFECTED PATIENTS; INTERFERON; IL-27;
PROLIFERATION; EXPRESSION; RECEPTOR
AB Interleukin (IL)-27 is a member of IL-12 family cytokine. We have previously reported that IL-27 inhibits human immunodefi ciency virus type-1 (HIV-1) replication in CD4(+) T cells and monocyte-derived macrophages, even though IL-12 enhances HIV-1 replication in primary CD4(+) T cells. Further study demonstrates that IL-27 induces antiviral genes including RNA-dependent protein kinase, oligoadenylate synthetase, and myxovirus protein in the same manner as interferon (IFN)-alpha. Neutralization assay using anti-IFN antibodies, real-time RT-PCR, and enzyme-linked immunosorbent assay demonstrated that IL-27 induces the antiviral genes without the induction of IFNs. IFN-alpha has been administered to hepatitis C virus (HCV)-infected patients as well as HCV/HIV-1 co-infected patients. Despite the improved immunotherapy, some patients are still failed to respond to the treatment. Since IL-27 induces IFN-alpha-like responses including the induction of antiviral genes, it was speculated that IL-27 may impact the replication of HCV. In this study, we evaluated the role of IL-27 on HCV replication using Huh7.5, an HCV permissive cell line. IL-27 induces STAT-1 and -3 in the cell line, and dose-dependently inhibited HCV. These data suggest that IL-27 may play a role in the development of a novel immunotherapeutic strategy for HCV and HCV/HIV co-infection.
C1 [Bharucha, Jennifer P.; Imamichi, Tomozumi] NCI Frederick, SAIC Frederick Inc, Lab Human Retrovirol, Clin Serv Program,Appl & Dev Directorate, Frederick, MD 21702 USA.
[Frank, Astrid C.; Zhang, Xiaozhen; Katsounas, Antonios; Kottilil, Shyamasundaran] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Imamichi, T (reprint author), NCI Frederick, SAIC Frederick Inc, Lab Human Retrovirol, Clin Serv Program,Appl & Dev Directorate, Bldg 550,Room 126,POB B, Frederick, MD 21702 USA.
EM timamichi@mail.nih.gov
FU National Cancer Institute, National Institute Health
[HHSN261200800001E]; National Institute of Allergy and Infectious
Disease
FX Authors thank H. C. Lane for guidance and support, and R. Dewar for a
critical reading. This project has been funded in whole or in part with
federal funds from the National Cancer Institute, National Institute
Health under contact No. HHSN261200800001E. The content of this
publication does not necessarily reflect the view or policies of the
department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the US
government. This research was supported by the National Institute of
Allergy and Infectious Disease.
NR 30
TC 22
Z9 23
U1 0
U2 4
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1079-9907
J9 J INTERF CYTOK RES
JI J. Interferon Cytokine Res.
PD JUN
PY 2010
VL 30
IS 6
BP 427
EP 431
DI 10.1089/jir.2009.0093
PG 5
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 609OW
UT WOS:000278667400007
PM 20235668
ER
PT J
AU Karpati, SK
Katz, SI
AF Karpati, Sarolta K.
Katz, Stephen I.
TI Common Goals and Challenges in Dermatological Research in Eastern Europe
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Editorial Material
C1 [Karpati, Sarolta K.] Semmelweis Univ, Dept Dermatol Venereol & Dermatooncol, H-1085 Budapest, Hungary.
[Katz, Stephen I.] NIAMSD, NIH, Bethesda, MD 20892 USA.
RP Karpati, SK (reprint author), Semmelweis Univ, Dept Dermatol Venereol & Dermatooncol, Maria Utca 41, H-1085 Budapest, Hungary.
EM titkarsag@bor.sote.hu
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD JUN
PY 2010
VL 130
IS 6
BP 1475
EP 1477
DI 10.1038/jid.2010.43
PG 3
WC Dermatology
SC Dermatology
GA 596DS
UT WOS:000277665200001
PM 20463665
ER
PT J
AU Kong, HH
Segre, JA
AF Kong, Heidi H.
Segre, Julia A.
TI Bridging the Translational Research Gap: A Successful Partnership
Involving a Physician and a Basic Scientist
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Editorial Material
ID DIVERSITY
C1 [Kong, Heidi H.] NHGRI, NIH, GMBB, Bethesda, MD 20892 USA.
[Kong, Heidi H.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Kong, HH (reprint author), NHGRI, NIH, GMBB, 49 Convent Dr,Bldg 49,Room 4A26,MSC 4442, Bethesda, MD 20892 USA.
EM konghe@mail.nih.gov; jsegre@nhgri.nih.gov
OI Kong, Heidi/0000-0003-4424-064X
FU Intramural NIH HHS [ZIA HG000180-10]
NR 4
TC 5
Z9 5
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD JUN
PY 2010
VL 130
IS 6
BP 1478
EP 1480
DI 10.1038/jid.2010.65
PG 3
WC Dermatology
SC Dermatology
GA 596DS
UT WOS:000277665200002
PM 20463666
ER
PT J
AU Tamura, D
DiGiovanna, JJ
Kraemer, KH
AF Tamura, Deborah
DiGiovanna, John J.
Kraemer, Kenneth H.
TI Founder Mutations in Xeroderma Pigmentosum
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Editorial Material
ID COCKAYNE-SYNDROME; GENE; TRICHOTHIODYSTROPHY; CODON
C1 [Tamura, Deborah; DiGiovanna, John J.; Kraemer, Kenneth H.] NCI, Dermatol Branch, Bethesda, MD 20892 USA.
[DiGiovanna, John J.] Brown Univ, Dept Dermatol, Div Dermatopathol, Warren Alpert Sch Med, Providence, RI 02912 USA.
RP Kraemer, KH (reprint author), NCI, Dermatol Branch, Bldg 37,Room 4002,MSC 4258, Bethesda, MD 20892 USA.
EM kraemerk@nih.gov
FU Intramural NIH HHS [ZIA BC004517-35]
NR 13
TC 9
Z9 9
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD JUN
PY 2010
VL 130
IS 6
BP 1491
EP 1493
DI 10.1038/jid.2010.76
PG 3
WC Dermatology
SC Dermatology
GA 596DS
UT WOS:000277665200005
PM 20463673
ER
PT J
AU Jalili, A
Pashenkov, M
Kriehuber, E
Wagner, C
Nakano, H
Stingl, G
Wagner, SN
AF Jalili, Ahmad
Pashenkov, Mikhail
Kriehuber, Ernst
Wagner, Christine
Nakano, Hideki
Stingl, Georg
Wagner, Stephan N.
TI Induction of Targeted Cell Migration by Cutaneous Administration of a
DNA Vector Encoding a Biologically Active Chemokine CCL21
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Article
ID LYMPHOCYTIC-LEUKEMIA CELLS; LYMPHOID-TISSUE CHEMOKINE; HIGH ENDOTHELIAL
VENULES; MICE LACKING EXPRESSION; MEMORY T-CELLS; DENDRITIC CELLS; CD40
LIGATION; PERIPHERAL-TISSUES; IMMUNE-RESPONSES; MEDIATED CONTROL
AB Skin inflammation can induce local expression of CCL21, which is subsequently drained to lymph nodes (LNs) influencing their cellular composition. To determine whether the same can be achieved by dermal administration of a plasmid DNA (pDNA) encoding CCL21, we generated a pDNA-based gene construct allowing high-level expression of CCL21. Expression and secretion of biologically active CCL21 were confirmed in vitro by immunohistochemistry, western blot analysis, ELISA, and transwell chemotactic assays. In vivo experiments showed cellular expression of transgenic CCL21 after particle-mediated gene gun delivery of pDNA into skin. CCL21 was expressed in the epidermis, consequently secreted into the upper dermis, and transported into the draining LNs, which resulted in increased CCL21 concentration, total cell number, and frequencies of CD11c(+) DCs and CD4(+)/CD62L(+) naive, CD4(+)/CD62L(-), and CD8(+)/CD62L(-) effector memory T-cells (expressing CCL21 receptors CCR7 or CXCR3), as well as retention of adoptively transferred T-lymphocytes, in the draining LNs of plt/plt mice (lacking endogenous expression of CCL21). Our studies show that biologically active CCL21 can be overexpressed by genetic means in vitro and in vivo. This strategy allows reconstitution of a genetic defect and colocalization of different cell types in the secondary lymphoid organs, an important prerequisite for targeted cell migration.
C1 [Jalili, Ahmad; Pashenkov, Mikhail; Kriehuber, Ernst; Wagner, Christine; Stingl, Georg; Wagner, Stephan N.] Med Univ Vienna, Dept Dermatol, DIAID, Allgemeines Krankenhaus, A-1090 Vienna, Austria.
[Nakano, Hideki] Natl Inst Environm Hlth Sci, Lab Resp Biol, NIH, Res Triangle Pk, NC USA.
RP Jalili, A (reprint author), Med Univ Vienna, Dept Dermatol, DIAID, Allgemeines Krankenhaus, Wahringer Gurtel 18-20, A-1090 Vienna, Austria.
EM ahmad.jalili@meduniwien.ac.at; stephan.wagner@meduniwien.ac.at
OI Wagner, Stephan/0000-0003-4941-7029
FU Austrian Academy of Sciences (Vienna, Austria) [20040]
FX We are grateful to Robert Zaugg (Vical Incorp., San Diego, CA) for
providing the VR1012 pDNA vector and Dr Kirsten Merz for critically
reading the paper. This work was supported by a grant (20040) from the
Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences
(Vienna, Austria).
NR 55
TC 2
Z9 2
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD JUN
PY 2010
VL 130
IS 6
BP 1611
EP 1623
DI 10.1038/jid.2010.31
PG 13
WC Dermatology
SC Dermatology
GA 596DS
UT WOS:000277665200019
PM 20182442
ER
PT J
AU Choi, W
Miyamura, Y
Wolber, R
Smuda, C
Reinhold, W
Liu, HF
Kolbe, L
Hearing, VJ
AF Choi, Wonseon
Miyamura, Yoshinori
Wolber, Rainer
Smuda, Christoph
Reinhold, William
Liu, Hongfang
Kolbe, Ludger
Hearing, Vincent J.
TI Regulation of Human Skin Pigmentation in situ by Repetitive UV Exposure:
Molecular Characterization of Responses to UVA and/or UVB
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Article
ID ULTRAVIOLET-RADIATION; GROWTH-FACTOR; HUMAN MELANOCYTES;
GENE-EXPRESSION; MELANIN CONTENT; DNA-DAMAGE; PHOTOCARCINOGENESIS;
DIFFERENTIATION; MECHANISMS; APOPTOSIS
AB UV radiation is a major environmental factor that affects pigmentation in human skin and can eventually result in various types of UV-induced skin cancers. The effects of various wavelengths of UV on melanocytes and other types of skin cells in culture have been studied, but little is known about gene expression patterns in situ following in situ exposure of human skin to different types of UV (UVA and/or UVB). Paracrine factors expressed by keratinocytes and/or fibroblasts that affect skin pigmentation might be regulated differently by UV, as might their corresponding receptors expressed on melanocytes. To test the hypothesis that different mechanisms are involved in the pigmentary responses of the skin to different types of UV, we used immunohistochemical and whole human genome microarray analyses to characterize human skin in situ to examine how melanocyte-specific proteins and paracrine melanogenic factors are regulated by repetitive exposure to different types of UV compared with unexposed skin as a control. The results show that gene expression patterns induced by UVA or UVB are distinct-UVB eliciting dramatic increases in a large number of genes involved in pigmentation as well as in other cellular functions, whereas UVA had little or no effect on these. The expression patterns characterize the distinct responses of the skin to UVA or UVB, and identify several potential previously unidentified factors involved in UV-induced responses of human skin.
C1 [Choi, Wonseon; Miyamura, Yoshinori; Hearing, Vincent J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Wolber, Rainer; Smuda, Christoph; Kolbe, Ludger] Beiersdorf AG, Skin Res Ctr, Res & Dev, Hamburg, Germany.
[Reinhold, William; Liu, Hongfang] NCI, Genom & Bioinformat Grp, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA.
[Liu, Hongfang] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA.
RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 2132,MSC 4256, Bethesda, MD 20892 USA.
EM hearingv@nih.gov
FU National Cancer Institute at NIH
FX We thank Sergio G. Coelho for helping with the UV spectra graph. This
research was supported in part by the Intramural Research Program of the
National Cancer Institute at NIH.
NR 53
TC 35
Z9 35
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD JUN
PY 2010
VL 130
IS 6
BP 1685
EP 1696
DI 10.1038/jid.2010.5
PG 12
WC Dermatology
SC Dermatology
GA 596DS
UT WOS:000277665200026
PM 20147966
ER
PT J
AU Green, RM
AF Green, Ronald M.
TI Political Interventions in US Human Embryo Research: An Ethical
Assessment
SO JOURNAL OF LAW MEDICINE & ETHICS
LA English
DT Article
AB For more than 30 years, beginning with the Reagan administration's refusal to support and provide oversight for embryo research, and continuing to the present in congressionally imposed limits on funding for such research, progress in infertility medicine and the development of stem cell therapies has been seriously delayed by a series of political interventions. In almost all cases, these interventions result from a view of the moral status of human embryo premised largely on religious assumptions. Although some believe that these interventions are valid expressions of religious values in the public sector, it is argued here that they, in fact, contradict Rawls's conception of public reasoning. Both the prohibition of research involving the human embryo as well as bans on federal funding for embryo-related research place the particular religious views of some citizens above the pressing health needs of almost all, and thus violate the ideal of civility implicit in the Rawlsian standard.
C1 [Green, Ronald M.] Dartmouth Coll, Relig Dept, Study Eth & Human Values, Hanover, NH 03755 USA.
[Green, Ronald M.] NHGRI, Off Genome Eth, NIH, Bethesda, MD 20892 USA.
RP Green, RM (reprint author), Dartmouth Coll, Relig Dept, Study Eth & Human Values, Hanover, NH 03755 USA.
NR 28
TC 3
Z9 3
U1 0
U2 4
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1073-1105
J9 J LAW MED ETHICS
JI J. Law Med. Ethics
PD SUM
PY 2010
VL 38
IS 2
BP 220
EP +
PG 10
WC Ethics; Law; Medical Ethics; Medicine, Legal
SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal
Medicine
GA 620XB
UT WOS:000279534400006
PM 20579245
ER
PT J
AU Shah, S
Wendler, D
AF Shah, Seema
Wendler, David
TI Interpretation of the Subjects' Condition Requirement: A Legal
Perspective
SO JOURNAL OF LAW MEDICINE & ETHICS
LA English
DT Article
AB The U.S. Federal regulations allow institutional review boards (IRBs) to approve non-beneficial pediatric research when the risks are a minor increase over minimal, provided that the research is likely to develop generalizable knowledge about the subjects' disorder or condition. This "subjects' condition" requirement is quite controversial; commentators have argued for a variety of interpretations. Despite this considerable disagreement in the literature, there have not been any attempts to apply principles of legal interpretation to determine how the subjects' Condition requirement should be understood.
C1 [Shah, Seema; Wendler, David] NIH, Unit Vulnerable Populat, Dept Bioeth, Ctr Clin, Bethesda, MD USA.
[Shah, Seema] NIH, Div Aids, Bethesda, MD USA.
RP Shah, S (reprint author), NIH, Unit Vulnerable Populat, Dept Bioeth, Ctr Clin, Bethesda, MD USA.
FU NIH
FX This research was supported by the Intramural Research Program of the
NIH, out of the Warren G. Magnussen Clinical Center. The opinions
expressed here are the views of the authors. They do not represent any
position or policy of the U.S. National Institutes of Health, the Public
Health Service, or the Department of Health and Human Services.
NR 18
TC 2
Z9 2
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1073-1105
J9 J LAW MED ETHICS
JI J. Law Med. Ethics
PD SUM
PY 2010
VL 38
IS 2
BP 365
EP +
PG 10
WC Ethics; Law; Medical Ethics; Medicine, Legal
SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal
Medicine
GA 620XB
UT WOS:000279534400019
PM 20579233
ER
PT J
AU Shen, J
Xiang, Y
AF Shen, Jun
Xiang, Yun
TI High fidelity magnetic resonance imaging by frequency sweep encoding and
Fourier decoding
SO JOURNAL OF MAGNETIC RESONANCE
LA English
DT Article
DE Magnetic resonance imaging; Encoding; Decoding; Field distortion
ID SINGLE-SCAN; INHOMOGENEOUS FIELDS; 11.7 TESLA; RAT-BRAIN; NMR;
ACQUISITION; SEQUENCE; IMAGES; PHASE; MRI
AB Using a RF pulse with linear frequency sweep and a simultaneous encoding gradient, magnetization is sequentially excited accompanied by a quadratic phase profile. This quadratic dependence of magnetization phase on position dephases magnetization away from its vertices, allowing direct spatial encoding and image formation in the time domain. In this work, we show that Fourier decoding or least square fitting in combination with frequency sweep spatial encoding schemes can generate high fidelity images and we also extend spatial encoding to include nonlinear frequency sweep. Application to in vivo multiscan susceptibility-weighted imaging is demonstrated. Our results show that Fourier-decoded, spatially encoded images compare favorably with conventional high resolution images while preserving the unique features of sequential excitation. Published by Elsevier Inc.
C1 [Shen, Jun; Xiang, Yun] NIMH, Mol Imaging Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Shen, J (reprint author), NIMH, Mol Imaging Branch, Intramural Res Program, NIH, Bldg 10,Rm 2D51A,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM shenj@intra.nimh.nih.gov
FU NIH, NIMH
FX This work is supported by the Intramural Research Program of the NIH,
NIMH.
NR 24
TC 13
Z9 13
U1 2
U2 10
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1090-7807
J9 J MAGN RESON
JI J. Magn. Reson.
PD JUN
PY 2010
VL 204
IS 2
BP 200
EP 207
DI 10.1016/j.jmr.2010.02.014
PG 8
WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical;
Spectroscopy
SC Biochemistry & Molecular Biology; Physics; Spectroscopy
GA 602TS
UT WOS:000278162300005
PM 20223688
ER
PT J
AU Thurber, KR
Yau, WM
Tycko, R
AF Thurber, Kent R.
Yau, Wai-Ming
Tycko, Robert
TI Low-temperature dynamic nuclear polarization at 9.4 T with a 30 mW
microwave source
SO JOURNAL OF MAGNETIC RESONANCE
LA English
DT Article
DE Solid state nuclear magnetic resonance; Sensitivity enhancement;
Hyperpolarization; Nitroxide; TEMPO; Spin lattice relaxation;
Paramagnetic relaxation
ID SOLID-STATE NMR; MAGNETIC-RESONANCE; CONFORMATIONAL DISTRIBUTIONS;
PARAMAGNETIC RELAXATION; FREE-RADICALS; HIV-1 GP120; C-13 NMR; V3 LOOP;
PROTEIN; DNP
AB Dynamic nuclear polarization (DNP) can provide large signal enhancements in nuclear magnetic resonance (NMR) by transfer of polarization from electron spins to nuclear spins. We discuss several aspects of DNP experiments at 9.4 T (400 MHz resonant frequency for (1)H, 264 GHz for electron spins in organic radicals) in the 7-80 K temperature range, using a 30 mW, frequency-tunable microwave source and a quasi-optical microwave bridge for polarization control and low-loss microwave transmission. In experiments on frozen glycerol/water doped with nitroxide radicals, DNP signal enhancements up to a factor of 80 are observed (relative to 1H NMR signals with thermal equilibrium spin polarization). The largest sensitivity enhancements are observed with a new triradical dopant, DOTOPA-TEMPO. Field modulation with a 10 G root-mean-squared amplitude during DNP increases the nuclear spin polarizations by up to 135%. Dependencies of 1H NMR signal amplitudes, nuclear spin relaxation times, and DNP build-up times on the dopant and its concentration, temperature, microwave power, and modulation frequency are reported and discussed. The benefits of low-temperature DNP can be dramatic: the H spin polarization is increased approximately 1000-fold at 7 K with DNP, relative to thermal polarization at 80 k. Published by Elsevier Inc.
C1 [Thurber, Kent R.; Yau, Wai-Ming; Tycko, Robert] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Tycko, R (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5,Room 112, Bethesda, MD 20892 USA.
EM robertty@mail.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases of the
National Institutes of Health; NIH Intramural AIDS Targeted Antiviral
Program
FX We thank Bernie Howder for machining parts for our cryostat and Dr.
Murali C. Krishna for use of the X-band EPR spectrometer. We thank Dr.
Kan-Nian Hu for many useful discussions regarding DNP effects and
experimental methods. This work was supported by the Intramural Research
Program of the National Institute of Diabetes and Digestive and Kidney
Diseases of the National Institutes of Health, and by the NIH Intramural
AIDS Targeted Antiviral Program. This study utilized the
high-performance computational capabilities of the Biowulf Linux cluster
at the NIH (http://www.biowulf.nih.gov).
NR 60
TC 76
Z9 77
U1 3
U2 37
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 JUN
PY 2010
VL 204
IS 2
BP 303
EP 313
DI 10.1016/j.jmr.2010.03.016
PG 11
WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical;
Spectroscopy
SC Biochemistry & Molecular Biology; Physics; Spectroscopy
GA 602TS
UT WOS:000278162300017
PM 20392658
ER
PT J
AU Hardy, KM
Booth, BW
Hendrix, MJC
Salomon, DS
Strizzi, L
AF Hardy, Katharine M.
Booth, Brian W.
Hendrix, Mary J. C.
Salomon, David S.
Strizzi, Luigi
TI ErbB/EGF Signaling and EMT in Mammary Development and Breast Cancer
SO JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA
LA English
DT Article
DE ErbB; EGF; EMT; Mammary development; Breast cancer
ID EPIDERMAL-GROWTH-FACTOR; EPITHELIAL-MESENCHYMAL TRANSITION; FACTOR
RECEPTOR FAMILY; EGF RECEPTOR; FACTOR-ALPHA; CARDIAC DEVELOPMENT; GLAND
DEVELOPMENT; HEART DEVELOPMENT; XENOPUS GASTRULATION; TARGETED
DISRUPTION
AB Activation of the ErbB family of receptor tyrosine kinases via cognate Epidermal Growth Factor (EGF)-like peptide ligands constitutes a major group of related signaling pathways that control proliferation, survival, angiogenesis and metastasis of breast cancer. In this respect, clinical trials with various ErbB receptor blocking antibodies and specific tyrosine kinase inhibitors have proven to be partially efficacious in the treatment of this heterogeneous disease. Induction of an embryonic program of epithelial-to-mesenchymal transition (EMT) in breast cancer, whereupon epithelial tumor cells convert to a more mesenchymal-like phenotype, facilitates the migration, intravasation, and extravasation of tumor cells during metastasis. Breast cancers which exhibit properties of EMT are highly aggressive and resistant to therapy. Activation of ErbB signaling can regulate EMT-associated invasion and migration in normal and malignant mammary epithelial cells, as well as modulating discrete stages of mammary gland development. The purpose of this review is to summarize current information regarding the role of ErbB signaling in aspects of EMT that influence epithelial cell plasticity during mammary gland development and tumorigenesis. How this information may contribute to the improvement of therapeutic approaches in breast cancer will also be addressed.
C1 [Hardy, Katharine M.; Hendrix, Mary J. C.; Strizzi, Luigi] Northwestern Univ, Feinberg Sch Med, Childrens Mem Res Ctr, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60614 USA.
[Booth, Brian W.] Clemson Univ, Inst Biol Interfaces Engn, Clemson, SC USA.
[Salomon, David S.] NCI, Lab Mammary Gland Biol, Bethesda, MD 20892 USA.
[Salomon, David S.] NCI, Tumorigenesis Lab, Bethesda, MD 20892 USA.
RP Strizzi, L (reprint author), Northwestern Univ, Feinberg Sch Med, Childrens Mem Res Ctr, Robert H Lurie Comprehens Canc Ctr, 2300 Childrens Plaza,Box 222, Chicago, IL 60614 USA.
EM lstrizzi@childrensmemorial.org
FU U.S. National Institutes of Health (NIH); NIH [CA59702, CA121205];
Eisenberg Scholar Research Award
FX This work is supported by the U.S. National Institutes of Health (NIH)
intramural funding, NIH extramural grants (CA59702 and CA121205) and the
Eisenberg Scholar Research Award. We apologize to authors whose work was
not mentioned directly.
NR 93
TC 71
Z9 74
U1 3
U2 8
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1083-3021
J9 J MAMMARY GLAND BIOL
JI J. Mammary Gland Biol. Neoplasia
PD JUN
PY 2010
VL 15
IS 2
BP 191
EP 199
DI 10.1007/s10911-010-9172-2
PG 9
WC Oncology; Endocrinology & Metabolism; Physiology
SC Oncology; Endocrinology & Metabolism; Physiology
GA 611QR
UT WOS:000278835900006
PM 20369376
ER
PT J
AU Ogge, G
Romero, R
Chaiworapongsa, T
Gervasi, MT
Pacora, P
Erez, O
Kusanovic, JP
Vaisbuch, E
Mazaki-Tovi, S
Gotsch, F
Mittal, P
Kim, YM
Hassan, SS
AF Ogge, Giovanna
Romero, Roberto
Chaiworapongsa, Tinnakorn
Gervasi, Maria Teresa
Pacora, Percy
Erez, Offer
Kusanovic, Juan Pedro
Vaisbuch, Edi
Mazaki-Tovi, Shali
Gotsch, Francesca
Mittal, Pooja
Kim, Yeon Mee
Hassan, Sonia S.
TI Leukocytes of pregnant women with small-for-gestational age neonates
have a different phenotypic and metabolic activity from those of women
with preeclampsia
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE SGA; hypertension; pregnancy; maternal systemic inflammation; leukocyte
phenotype; oxidative burst; flow cytometry; mean channel brightness;
CD62L; CD11b
ID INTRAUTERINE GROWTH-RETARDATION; TUMOR-NECROSIS-FACTOR; UTERINE ARTERY
DOPPLER; GENERALIZED SHWARTZMAN REACTION; ENDOTHELIAL-CELL DYSFUNCTION;
CIRCULATING IMMUNE-COMPLEXES; PERIPHERAL-BLOOD LEUKOCYTES; TISSUE FACTOR
EXPRESSION; LATE-ONSET PREECLAMPSIA; BED SPIRAL ARTERIES
AB Objective. Preeclampsia and pregnancies complicated by small-for-gestational age (SGA) neonates share several underlying mechanisms of disease. However, while an exaggerated systemic maternal inflammatory response is regarded as one of the hallmarks of the pathogenesis of preeclampsia, the presence of a similar systemic intra-vascular inflammation in mothers of SGA neonates without hypertension is controversial. The aim of this study was to determine phenotypic and metabolic changes in granulocytes and monocytes of women who develop preeclampsia and those who deliver an SGA neonate, compared to normal pregnant women.
Methods. This cross-sectional study included patients with a normal pregnancy (n 33), preeclampsia (n = 33), and an SGA without preeclampsia (n = 33), matched for gestational age at blood sample collection. Granulocyte and monocyte phenotypes were determined by flow cytometry, using monoclonal antibodies against selective cluster of differentiation (CD) antigens. The panel of antibodies included the following: CD11b, CD14, CD16, CD18, CD49d, CD62L, CD64, CD66b, and HLA-DR. Intracellular reactive oxygen species (iROS) were assessed at the basal state and after stimulation (oxidative burst). Results were reported as mean channel brightness (MCB) or intensity of detected fluorescence. Analysis was conducted with non-parametric statistics. A p-value < 0.01 was considered statistically significant.
Results. (1) Women who delivered an SGA neonate had a higher MCB of CD11b in granulocytes and monocytes than those with a normal pregnancy (p < 0.001 for both); (2) patients with preeclampsia had a lower median MCB of CD62L in granulocytes (p = 0.006) and a higher median basal iROS and oxidative burst in monocytes than women with an SGA neonate (p = 0.003 and p = 0.002, respectively).
Conclusion. Pregnancies complicated by the delivery of an SGA neonate are characterized by a higher activation of maternal peripheral leukocytes than in normal pregnancies, but lower than in pregnancies complicated by preeclampsia.
C1 [Romero, Roberto] Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, Detroit, MI 48201 USA.
[Ogge, Giovanna; Romero, Roberto; Chaiworapongsa, Tinnakorn; Pacora, Percy; Erez, Offer; Kusanovic, Juan Pedro; Vaisbuch, Edi; Mazaki-Tovi, Shali; Gotsch, Francesca; Mittal, Pooja; Kim, Yeon Mee; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Romero, Roberto; Chaiworapongsa, Tinnakorn; Erez, Offer; Kusanovic, Juan Pedro; Vaisbuch, Edi; Mazaki-Tovi, Shali; Mittal, Pooja; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.
[Gervasi, Maria Teresa] Azienda Osped Padova, Dept Obstet & Gynecol, Padua, Italy.
[Kim, Yeon Mee] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA.
RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM prbchiefstaff@med.wayne.edu
RI Ogge, Giovanna/G-6109-2011;
OI Vaisbuch, Edi/0000-0002-8400-9031
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, NIH, DHHS
FX This research was supported by the Perinatology Research Branch,
Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, NIH, DHHS.
NR 144
TC 13
Z9 16
U1 0
U2 1
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1476-7058
EI 1476-4954
J9 J MATERN-FETAL NEO M
JI J. Matern.-Fetal Neonatal Med.
PD JUN
PY 2010
VL 23
IS 6
BP 476
EP 487
DI 10.3109/14767050903216033
PG 12
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 612VB
UT WOS:000278931300002
PM 19916874
ER
PT J
AU Cohen, JI
Fahle, G
Kemp, MA
Apakupakul, K
Margolis, TP
AF Cohen, Jeffrey I.
Fahle, Gary
Kemp, Margaret A.
Apakupakul, Kathleen
Margolis, Todd P.
TI Human Herpesvirus 6-A, 6-B, and 7 in Vitreous Fluid Samples
SO JOURNAL OF MEDICAL VIROLOGY
LA English
DT Article
DE HHV-6A; HHV-6B; HHV-7; retinitis; iritis; vitritis
ID POLYMERASE-CHAIN-REACTION; REAL-TIME PCR; MULTIPLE-SCLEROSIS;
BRAIN-TISSUE; HUMAN-HERPESVIRUS-6; PREVALENCE; AIDS; CYTOMEGALOVIRUS;
IDENTIFICATION; RETINITIS
AB Human herpesvirus 6 and 7 (HHV-6, HHV-7) have been associated with several neurologic syndromes and have been detected in nervous tissue from healthy persons, however, only two cases of HHV-6A have been reported to be associated with intraocular inflammatory disease Vitreous fluid was tested from 101 patients, including 69 samples from patients with ocular inflammation including CMV retinitis, idiopathic retina's, iritis, and varitis, for HHV-6A, HHV-6B, and HHV-7 DNA by PCR HHV-6A DNA (4,950 copies per ml) was detected in vitreous fluid from one patient with CMV retina's, HHV-6B DNA (10,140 copies per ml) was detected in vitreous fluid from one patient with idiopathic ocular inflammation in the absence of CMV DNA, and HHV-7 was not detected in any of the vitreous samples. HHV-6A, HHV-6B, and HHV-7 DNA are detectable in less than 2% of vitreous samples in patients with ocular inflammation. J. Med. Virol. 82:996 999, 2010. (C) 2010 Wiley-Liss. Inc
C1 [Cohen, Jeffrey I.] NIAID, Med Virol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Fahle, Gary; Kemp, Margaret A.] NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA.
[Apakupakul, Kathleen; Margolis, Todd P.] Univ Calif San Francisco, Francis I Proctor Fdn, San Francisco, CA 94143 USA.
[Apakupakul, Kathleen; Margolis, Todd P.] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA.
RP Cohen, JI (reprint author), NIAID, Med Virol Sect, Lab Clin Infect Dis, NIH, Bldg 10,Rm 11N234,10 Ctr Dr,MSC 1888, Bethesda, MD 20892 USA.
FU National Institute of Allergy and Infectious Diseases; Warren G Magnuson
Clinical Center; Littlefield Foundation and Trust; Research to Prevent
Blindness (New York. NY)
FX Grant sponsor Intramural research programs of The National Institute of
Allergy and Infectious Diseases, Grant sponsor Warren G Magnuson
Clinical Center, Grant sponsor Littlefield Foundation and Trust (to T P
M), Grant sponsor Research to Prevent Blindness (New York. NY) (to T P
M)
NR 18
TC 11
Z9 11
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0146-6615
J9 J MED VIROL
JI J. Med. Virol.
PD JUN
PY 2010
VL 82
IS 6
BP 996
EP 999
DI 10.1002/jmv.21751
PG 4
WC Virology
SC Virology
GA 587HR
UT WOS:000276981700011
PM 20419813
ER
PT J
AU Esteban, LE
Rota, RP
Gentsch, JR
Jiang, BM
Esona, M
Glass, RI
Glikmann, G
Castello, AA
AF Esteban, Laura E.
Rota, Rosana P.
Gentsch, Jon R.
Jiang, Baoming
Esona, Mathew
Glass, Roger I.
Glikmann, Graciela
Castello, Alejandro A.
TI Molecular Epidemiology of Group A Rotavirus in Buenos Aires, Argentina
2004-2007: Reemergence of G2P[4] and Emergence of G9P[8] Strains
SO JOURNAL OF MEDICAL VIROLOGY
LA English
DT Article
DE rotavirus; genotype; diarrhea, vaccine
ID POLYMERASE CHAIN-REACTION; RIO-DE-JANEIRO; VACCINATED POPULATION;
HOSPITALIZED CHILDREN; PHYLOGENETIC ANALYSIS; DEVELOPING-COUNTRIES;
NUCLEIC-ACID; GENOTYPE G9; BRAZIL; DIARRHEA
AB Detection and characterization of group A rotavirus in Buenos Aires, Argentina, was conducted on 710 fecal samples from children 0-15 years old collected between 2004 and 2007. Rotavirus was detected in 140 (19.7%) samples with G9P[8] (30.0%) and G2P[4] (21.4%) as the most common genotypes Mixed (G and/or P) infections accounted for 17.9% of the samples and the emerging G12 strain was detected during 2004 (3.5%) and 2007 (2.5%). Genotype G2 was the most prevalent during 2004 (43.9%) and 2007 (57.5%) and G9 during 2005 (58.0%) and 2006 (61.5%). Analysis of genotype prevalences from studies performed since 1996 in the same area showed striking natural fluctuations in G and P genotype frequencies. In particular, G2P[4] strains disappeared after 1999 and reemerged in 2004 to become the predominant strain by 2007 with a concomitant major decrease in G1 P[8] prevalence. The VP7 genes from Argentinian G9 and G2 strains were sequenced and phylogenetic analysis was conducted in order to compare with sequences from strains isolated in regional countries reported previously. Several changes in the deduced amino acid sequence in antigenic regions of the VP7 protein from Argentinian and Brazilian strains were identified compared to vaccine strains. Overall, this study revealed relationships in the circulation of rotavirus strains in South American countries and major replacements in dominant genotypes, including the virtual disappearance of G1P[8] strains in a non-vaccinated population. High numbers of mixed infections speeding up evolution, circulation of rare serotypes, and antigenic drift could, eventually, become challenges for new vaccines. J. Med. Virol. 82:1083-1093, 2010. (C) 2010 Wiley-Liss, Inc
C1 [Esteban, Laura E.; Rota, Rosana P.; Glikmann, Graciela; Castello, Alejandro A.] Univ Nacl Quilmes, LIV, Buenos Aires, DF, Argentina.
[Rota, Rosana P.; Gentsch, Jon R.; Jiang, Baoming; Esona, Mathew; Glass, Roger I.; Castello, Alejandro A.] Ctr Dis Control & Prevent, Gastroenteritis & Resp Viruses Lab Branch, Div Viral Dis, US Dept HHS, Atlanta, GA USA.
[Glass, Roger I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Esteban, LE (reprint author), Univ Nacl Quilmes, LIV, Roque Saenz Pena 352,B1876BXD, Buenos Aires, DF, Argentina.
OI Castello, Alejandro/0000-0002-0586-1702
NR 52
TC 35
Z9 38
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0146-6615
J9 J MED VIROL
JI J. Med. Virol.
PD JUN
PY 2010
VL 82
IS 6
BP 1083
EP 1093
DI 10.1002/jmv.21745
PG 11
WC Virology
SC Virology
GA 587HR
UT WOS:000276981700024
PM 20419826
ER
PT J
AU Miller, FG
Truog, RD
Brock, DW
AF Miller, Franklin G.
Truog, Robert D.
Brock, Dan W.
TI The Dead Donor Rule: Can It Withstand Critical Scrutiny?
SO JOURNAL OF MEDICINE AND PHILOSOPHY
LA English
DT Article
DE causing death; medical ethics; organ donation
ID BRAIN-DEATH; CARDIAC DEATH; DEFINITION; ABANDON
AB Transplantation of vital organs has been premised ethically and legally on "the dead donor rule" (DDR)-the requirement that donors are determined to be dead before these organs are procured. Nevertheless, scholars have argued cogently that donors of vital organs, including those diagnosed as "brain dead" and those declared dead according to cardiopulmonary criteria, are not in fact dead at the time that vital organs are being procured. In this article, we challenge the normative rationale for the DDR by rejecting the underlying premise that it is necessarily wrong for physicians to cause the death of patients and the claim that abandoning this rule would exploit vulnerable patients. We contend that it is ethical to procure vital organs from living patients sustained on life support prior to treatment withdrawal, provided that there is valid consent for both withdrawing treatment and organ donation. However, the conservatism of medical ethics and practical concerns make it doubtful that the DDR will be abandoned in the near future. This leaves the current practice of organ transplantation based on the "moral fiction" that donors are dead when vital organs are procured.
C1 [Miller, Franklin G.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Truog, Robert D.] Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA.
[Miller, Franklin G.] NIH, Dept Bioeth, Bethesda, MD 20892 USA.
RP Miller, FG (reprint author), NIH, Dept Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
EM fmiller@nih.gov
FU Intramural NIH HHS
NR 23
TC 24
Z9 26
U1 0
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0360-5310
J9 J MED PHILOS
JI J. Med. Philos.
PD JUN
PY 2010
VL 35
IS 3
BP 299
EP 312
DI 10.1093/jmp/jhq019
PG 14
WC Ethics; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Biomedical Social Sciences
GA 611MO
UT WOS:000278819700004
PM 20439355
ER
PT J
AU Carpi, G
Holmes, EC
Kitchen, A
AF Carpi, Giovanna
Holmes, Edward C.
Kitchen, Andrew
TI The Evolutionary Dynamics of Bluetongue Virus
SO JOURNAL OF MOLECULAR EVOLUTION
LA English
DT Article
DE Bluetongue virus; Molecular evolution; Reassortment; Orbivirus
ID PHYLOGENETIC ANALYSIS; RNA VIRUSES; MEDITERRANEAN BASIN; MOLECULAR
SEQUENCES; UNITED-STATES; STRAINS; SUBSTITUTION; GENES; RATES;
RECOMBINATION
AB Bluetongue virus (BTV) is a midge-borne member of the genus Orbivirus that causes an eponymous debilitating livestock disease of great agricultural impact and which has expanded into Europe in recent decades. Reassortment among the ten segments comprising the double-stranded (ds) RNA genome of BTV has played an important role in generating the epidemic strains of this virus in Europe. In this study, we investigated the dynamics of BTV genome segment evolution utilizing time-structured data sets of complete sequences from four segments, totalling 290 sequences largely sampled from ruminant hosts. Our analysis revealed that BTV genome segments generally evolve under strong purifying selection and at substitution rates that are generally lower (mean rates of similar to 0.5-7 x 10(-4) nucleotide substitutions per site, per year) than vector-borne positive-sense viruses with single-strand (ss) RNA genomes. These also represent the most robust estimates of the nucleotide substitution rate in a dsRNA virus generated to date. Additionally, we determined that patterns of geographic structure and times to most recent common ancestor differ substantially between each segment, including a relatively recent origin for the diversity of segment 10 within the past millennium. Together, these findings demonstrate the effect of reassortment to decouple the evolutionary dynamics of BTV genome segments.
C1 [Holmes, Edward C.; Kitchen, Andrew] Penn State Univ, Dept Biol, Mueller Lab 609, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Carpi, Giovanna] IASMA Res & Innovat Ctr, Fdn Edmund Mach, Environm & Nat Resources Area, Trento, Italy.
[Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Kitchen, A (reprint author), Penn State Univ, Dept Biol, Mueller Lab 609, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
EM aak11@psu.edu
OI Holmes, Edward/0000-0001-9596-3552
NR 55
TC 21
Z9 26
U1 1
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0022-2844
J9 J MOL EVOL
JI J. Mol. Evol.
PD JUN
PY 2010
VL 70
IS 6
BP 583
EP 592
DI 10.1007/s00239-010-9354-y
PG 10
WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
Heredity
GA 611QS
UT WOS:000278836100005
PM 20526713
ER
PT J
AU Zhou, ZG
Wang, YL
Bryant, SH
AF Zhou, Zhigang
Wang, Yanli
Bryant, Stephen H.
TI QSAR models for predicting cathepsin B inhibition by small
molecules-Continuous and binary QSAR models to classify cathepsin B
inhibition activities of small molecules
SO JOURNAL OF MOLECULAR GRAPHICS & MODELLING
LA English
DT Article
DE Binary QSAR; Regression; Partial least squares; Docking; Cathepsin B
protein; Screening; PubChem bioassay
ID ATOM FORCE-FIELD; CYSTEINE PROTEASES; ALZHEIMERS-DISEASE; ACCURATE
DOCKING; PLASMA-MEMBRANE; DRUG DESIGN; BINDING; CANCER; PROTEIN;
IDENTIFICATION
AB Cathepsin B is a potential target for the development of drugs to treat several important human diseases. A number of inhibitors targeting this protein have been developed in the past several years. Recently, a group of small molecules were identified to have inhibitory activity against cathepsin B through high throughput screening (HTS) tests. In this study, traditional continuous and binary QSAR models were built to classify the biological activities of previously identified compounds and to distinguish active compounds from inactive compounds for drug development based on the calculated molecular and physicochemical properties. Strong correlations were obtained for the continuous QSAR models with regression correlation coefficients (r(2)) and cross-validated correlation coefficients (q(2)) of 0.77 and 0.61 for all compounds, and 0.82 and 0.68 for the compound set excluding 3 outliers, respectively. The models were further validated through the leave-one-out (LOO) method and the training-test set method. The binary models demonstrated a strong level of predictability in distinguishing the active compounds from inactive compounds with accuracies of 0.89 and 0.94 for active and inactive compounds, respectively, in non-cross-validated models. Similar results were obtained for the cross-validated models. Collectively, these results demonstrate the models' ability to discriminate between active and inactive compounds, suggesting that the models may be used to pre-screen compounds to facilitate compound optimization and to design novel inhibitors for drug development. Published by Elsevier Inc.
C1 [Zhou, Zhigang; Wang, Yanli; Bryant, Stephen H.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Bryant, SH (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA.
EM zhougeor@ncbi.nlm.nih.gov; bryant@ncbi.nlm.nih.gov
FU NIH; NLM
FX This research was supported by the Intramural Research Program of the
NIH and NLM. The authors would like to thank the NIH Fellows Editorial
Board (FEB) for reviewing the manuscript and the developers of Pymol
software for sharing the program to prepare the molecular figures used
in this paper.
NR 43
TC 7
Z9 7
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1093-3263
J9 J MOL GRAPH MODEL
JI J. Mol. Graph.
PD JUN
PY 2010
VL 28
IS 8
BP 714
EP 727
DI 10.1016/j.jmgm.2010.01.009
PG 14
WC Biochemical Research Methods; Biochemistry & Molecular Biology; Computer
Science, Interdisciplinary Applications; Crystallography; Mathematical &
Computational Biology
SC Biochemistry & Molecular Biology; Computer Science; Crystallography;
Mathematical & Computational Biology
GA 606HY
UT WOS:000278414800002
PM 20194042
ER
PT J
AU Blanco, IB
Astudillo, A
Iglesias, FD
Janciauskiene, S
Fernandez, VC
Alvaro, CG
Argiz, HC
de Serres, FJ
Bustillo, EF
AF Blanco Blanco, Ignacio
Astudillo, Aurora
Dominguez Iglesias, Francisco
Janciauskiene, Sabina
Carcaba Fernandez, Victoriano
Gallo Alvaro, Cesar
Canto Argiz, Hortensia
de Serres, Frederick Joseph
Fernandez Bustillo, Enrique
TI Intravenous Infusions of Purified Alpha-1 Antitripsyn Effectively
Controls Symptoms and Reverts Muscle Biopsy Changes in an MZ Alpha-1
Antitripsyn Deficiency and Fibromyalgia Syndrome Patient
SO JOURNAL OF MUSCULOSKELETAL PAIN
LA English
DT Article
DE Fibromyalgia syndrome; alpha-1 antitrypsin; alpha-1 antitrypsin
deficiency; alpha-1 antitrypsin augmentation therapy
ID ACTIVATED RECEPTORS; PAIN; ALPHA(1)-ANTITRYPSIN; ALPHA-1-ANTITRYPSIN;
PREVALENCE
AB Background: An MZ phenotype alpha-1 antitrypsin [AAT] deficiency and fibromyalgia syndrome [FMS] patient participated in a trial with AAT-intravenous augmentationtherapy [AAT-IV-AT] after failure of conventional therapeutic measures. Three quadricep biopsies were performed at different stages. The first one showed large aggregates of AAT and ubiquitin in myocytes and blood vessels, and moderate muscle atrophy, before AAT-IV-AT. The two remaining biopsies were performed while receiving AAT-IV-AT.
Findings: Remarkably good clinical response and histological improvement in the follow-up biopsies.
Conclusions: The clinical and histopathological efficacy of AAT-IV-AT evidenced in this patient should open new perspectives of research and management of AAT deficiency and FMS patients.
C1 [Blanco Blanco, Ignacio; Canto Argiz, Hortensia] Valle Nalon Hosp, Dept Internal Med, Unit Resp Dis, Principado De Asturias, Spain.
[Astudillo, Aurora] Hosp Univ Cent Asturias, Dept Pathol, Principado De Asturias, Spain.
[Dominguez Iglesias, Francisco] Hosp Valle Nalon, Dept Pathol, Principado De Asturias, Spain.
[Janciauskiene, Sabina] Malmo Univ Hosp, Dept Med, Malmo, Sweden.
[de Serres, Frederick Joseph] NIEHS, Ctr Evaluat Risks Human Reprod, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Fernandez Bustillo, Enrique] Cent Univ Hosp Asturias, Biostat Unit, Principado De Asturias, Spain.
RP Blanco, IB (reprint author), Valle Nalon Hosp, Dept Internal Med, Unit Resp Dis, Principado De Asturias, Spain.
FU Carlos III Health Institute [Ministry of Health and Consumption, Madrid,
Spain [PI061798]; Biohealth research office [OIB] of the Principado de
Asturias
FX This study has been endorsed by the Carlos III Health Institute
[Ministry of Health and Consumption, Madrid, Spain, project PI061798,
October 2006] and by the Biohealth research office [OIB] of the
Principado de Asturias.
NR 12
TC 1
Z9 2
U1 0
U2 0
PU HAWORTH PRESS INC
PI BINGHAMTON
PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA
SN 1058-2452
J9 J MUSCULOSKELET PAIN
JI J. Musculoskelet. Pain
PD JUN
PY 2010
VL 18
IS 2
BP 167
EP 172
DI 10.3109/10582452.2010.483962
PG 6
WC Rehabilitation; Rheumatology
SC Rehabilitation; Rheumatology
GA 624FJ
UT WOS:000279801800009
ER
PT J
AU Haughey, NJ
Xu, H
Bandaru, VVR
Wang, Y
Mattson, M
AF Haughey, N. J.
Xu, H.
Bandaru, V. V. R.
Wang, Y.
Mattson, M.
TI Temporal and spatial regulation of NMDA receptor trafficking by neutral
sphingomyelinase generated ceramide
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT 4th ISN Special Conference on Membrane Domains in CNS Physiology and
Pathology
CY MAY 22-26, 2010
CL Erice, ITALY
SP ISN
C1 [Haughey, N. J.; Xu, H.; Bandaru, V. V. R.] Johns Hopkins Univ, Sch Med, Dept Neurol, Div Neuroimmunol & Neurol Infect, Baltimore, MD USA.
[Wang, Y.; Mattson, M.] NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD JUN
PY 2010
VL 113
SU 1
MA 34
BP 10
EP 11
PG 2
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 603SV
UT WOS:000278229300035
ER
PT J
AU Iwabuchi, K
Ichikawa, N
Kurihara, H
Kobayashi, T
Hozumi, K
Yamada, Y
Arikawa-Hirasawa, E
AF Iwabuchi, K.
Ichikawa, N.
Kurihara, H.
Kobayashi, T.
Hozumi, K.
Yamada, Y.
Arikawa-Hirasawa, E.
TI Binding of laminin-1 to monosialoganglioside GM1 in membrane
microdomains is essential for neurite outgrowth
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT 4th ISN Special Conference on Membrane Domains in CNS Physiology and
Pathology
CY MAY 22-26, 2010
CL Erice, ITALY
SP ISN
C1 [Iwabuchi, K.] Inst Environm & Gender Specif Med, Chiba, Japan.
[Ichikawa, N.; Arikawa-Hirasawa, E.] Res Inst Dis Old Age, Tokyo, Japan.
[Kurihara, H.] Juntendo Univ, Sch Med, Dept Anat, Tokyo 113, Japan.
[Kobayashi, T.] Riken Adv Sci Inst, Lipid Biol Lab, Saitama, Japan.
[Hozumi, K.] Shriners Hosp Children, Res Ctr, Portland, OR 97201 USA.
[Yamada, Y.] NIDCR, Lab Cell & Dev Biology, NIH, Bethesda, MD USA.
RI Kobayashi, Toshihide/B-6298-2015
OI Kobayashi, Toshihide/0000-0002-4811-7270
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD JUN
PY 2010
VL 113
SU 1
MA 43
BP 13
EP 13
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 603SV
UT WOS:000278229300044
ER
PT J
AU Panicker, LM
Zhang, JH
Posokhova, E
Gastinger, MJ
Martemyanov, KA
Simonds, WF
AF Panicker, Leelamma M.
Zhang, Jian-Hua
Posokhova, Ekaterina
Gastinger, Matthew J.
Martemyanov, Kirill A.
Simonds, William F.
TI Nuclear localization of the G protein beta 5/R7-regulator of G protein
signaling protein complex is dependent on R7 binding protein
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE DEP domain; heterotrimeric G protein; palmitoylation; R7 binding
protein; regulator of G protein signaling; subcellular localization
ID HETEROTRIMERIC G-PROTEINS; MEMBRANE ANCHOR; RGS PROTEINS; IN-VIVO;
NEURONS; DOMAIN; BRAIN; REGULATORS; SUBUNITS; R9AP
AB P>The neuronally expressed G beta(5) subunit is the most structurally divergent among heterotrimeric G beta isoforms and unique in its ability to heterodimerize with the R7 subfamily of regulator of G protein signaling (RGS) proteins. The complex between G beta(5) and R7-type RGS proteins targets the cell nucleus by an unknown mechanism. Although the nuclear targeting of the G beta(5)/R7-RGS complex is proposed to involve the binding of R7-binding protein (R7BP), this theory is challenged by the observations that endogenous R7BP is palmitoylated, co-localizes strongly with the plasma membrane, and has never been identified in the cytosol or nucleus of native neurons or untreated cultured cells. We show here mutant RGS7 lacking the N-terminal Disheveled, EGL-10, Pleckstrin homology domain is expressed in transfected cells but, unlike wild-type RGS7, is excluded from the cell nucleus. As the Disheveled, EGL-10, Pleckstrin homology domain is essential for R7BP binding to RGS7, we studied the subcellular localization of G beta(5) in primary neurons and brain from mice deficient in R7BP. The level of endogenous nuclear G beta(5) and RGS7 in neurons and brains from R7BP knockout mice is reduced by 50-70%. These results suggest that R7BP contributes significantly to the nuclear localization of endogenous G beta(5)/R7-RGS complex in brain.
C1 [Panicker, Leelamma M.; Zhang, Jian-Hua; Simonds, William F.] NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA.
[Posokhova, Ekaterina; Martemyanov, Kirill A.] Univ Minnesota, Dept Pharmacol, Minneapolis, MN 55455 USA.
[Gastinger, Matthew J.] NIAID, Res Technol Branch, NIH, Bethesda, MD 20892 USA.
RP Simonds, WF (reprint author), NIDDK, Metab Dis Branch, NIH, Bldg 10,Room 8C-101,10 Ctr Dr,MSC 1752, Bethesda, MD 20892 USA.
EM wfs@helix.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases; NIH
[DA021743, DA026405]
FX None of the authors has a financial or any other conflict of interest.
This research was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases (WFS)
and grants NIH DA021743 and NIH DA026405 (KAM).
NR 33
TC 12
Z9 12
U1 1
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD JUN
PY 2010
VL 113
IS 5
BP 1101
EP 1112
DI 10.1111/j.1471-4159.2010.06616.x
PG 12
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 591SG
UT WOS:000277323000003
PM 20100282
ER
PT J
AU Shamir, A
Buonanno, A
AF Shamir, Alon
Buonanno, Andres
TI Molecular and cellular characterization of Neuregulin-1 type IV isoforms
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE ErbB4 receptor; Neuregulin; Neuregulin-ErbB signaling; polymorphism;
schizophrenia; sub-cellular localization
ID LONG-TERM POTENTIATION; SYNAPTIC PLASTICITY; HIPPOCAMPAL-NEURONS; NMDA
RECEPTORS; NERVOUS-SYSTEM; NRG1 GENE; SCHIZOPHRENIA; CELLS; EXPRESSION;
SYNAPSES
AB P>Numerous genetic studies associated the Neuregulin 1 (NRG1) Icelandic haplotype (HAP(ice)), and its single nucleotide polymorphism SNP8NRG243177 [T/T], with schizophrenia. Because SNP8NRG243177 [T/T] has characteristics of a functional polymorphism that maps close to NRG1 type IV coding sequences, our initial goal was to map precisely the human type IV transcription initiation site. We determined that the initiation site is 23 bp upstream of the previously reported type IV exon, and that no other transcripts map to the SNP8NRG243177 region. Because NRG1 type IV transcripts are specific to human, we isolated full-length NRG1 type IV cDNAs from human hippocampi and expressed them in non-neural cells and dissociated rat hippocampal neurons to study protein expression, processing and function. Using an antiserum we generated against the NRG1 type IV-specific N-terminus, we found that the protein is targeted to the cell surface where PKC activation promotes its cleavage and release of the extracellular domain. Conditioned medium derived from type IV expressing cells stimulates ErbB receptor phosphorylation, as well as downstream Akt and Erk signaling, demonstrating that NRG1 type IV possesses biological activity similar to other releasable NRG1 isoforms. To study the subcellular targeting of distinct isoforms, neurons were transfected with the Ig-domain-containing NRG1 types I and IV, or the cysteine-rich domain type III isoform. Three dimensional confocal images from transfected neurons indicate that, whereas all isoforms are expressed on somato-dendritic membranes, only the type III-cysteine-rich domain isoform is detectable in distal axons. These results suggest that NRG1 type IV expression levels associated with SNP8NRG243177 [T/T] can selectively modify signaling of NRG1 released from somato-dendritic compartments, in contrast to the type III NRG1 that is also associated with axons.
C1 [Buonanno, Andres] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
RP Buonanno, A (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Neurobiol Sect, NIH, Bldg 35,Room 2C-1000,35 Lincoln Dr, Bethesda, MD 20892 USA.
EM buonanno@mail.nih.gov
FU Eunice Shriver Kennedy NICHD Intramural Research Program
FX The authors thank Dr. Vullhorst for contributing to the characterization
of the HL5792 antibody, Dr. Karavanova for preparation of neuronal
cultures, and Dr Schram from the NICHD Microscopy Imaging Core for
helping with the confocal microscope and assembly of 3D images. We also
thank Drs. Vullhorst and Neddens for critical reading of the manuscript.
We are grateful for the financial support from the Eunice Shriver
Kennedy NICHD Intramural Research Program.
NR 61
TC 14
Z9 14
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD JUN
PY 2010
VL 113
IS 5
BP 1163
EP 1176
DI 10.1111/j.1471-4159.2010.06677.x
PG 14
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 591SG
UT WOS:000277323000008
PM 20218976
ER
PT J
AU Haque, R
Ali, FG
Biscoglia, R
Abey, J
Weller, J
Klein, D
Iuvone, PM
AF Haque, Rashidul
Ali, Fatima G.
Biscoglia, Rebecca
Abey, Jane
Weller, Joan
Klein, David
Iuvone, P. Michael
TI CLOCK and NPAS2 have overlapping roles in the circadian oscillation of
arylalkylamine N-acetyltransferase mRNA in chicken cone photoreceptors
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE circadian clock genes; circadian rhythms; melatonin; retina; RNA
interference; transcription factors
ID MELATONIN SYNTHESIS; RETINAL PHOTORECEPTORS; MAMMALIAN RETINA;
PINEAL-GLAND; KAINIC ACID; MOUSE CLOCK; REV-ERB; TRANSCRIPTION;
COMPONENTS; EXPRESSION
AB P>Circadian clocks in vertebrates are thought to be composed of transcriptional-translational feedback loops involving a highly conversed set of 'clock genes' namely, period (Per1-3) and cryptochrome (Cry1-2), which encode negative transcriptional regulators; and Bmal1, Clock, and Npas2, which encode positive regulators. Aanat, which encodes arylalkylamine N-acetyltransferase (AANAT), the key regulatory enzyme that drives the circadian rhythm of melatonin synthesis, contains a circadian E-box element (CACGTG) in its proximal promoter that is potentially capable of binding CLOCK : BMAL1 and NPAS2 : BMAL1 heterodimers. The present study was conducted to investigate whether CLOCK and/or NPAS2 regulates Aanat expression in photoreceptor cells. Npas2 and Clock are both expressed in photoreceptor cells in vivo and in vitro. To assess the roles of CLOCK and NPAS2 in Aanat expression, gene-specific micro RNA vectors were used to knock down expression of these clock genes in photoreceptor-enriched cell cultures. The knockdown of CLOCK protein significantly reduced the circadian expression of Npas2, Per2, and Aanat transcripts but had no effect on the circadian rhythm of Bmal1 transcript level. The knockdown of NPAS2 significantly damped the circadian rhythm of Aanat mRNAs but had no effect on circadian expression of any of clock genes examined, except Npas2 itself. Chromatin immunoprecipitation studies indicated that both CLOCK and NPAS2 bound to the Aanat promoter in situ. Thus, CLOCK and NPAS2 have overlapping roles in the clock output pathway that regulates the rhythmic expression of Aanat in photoreceptors. However, CLOCK plays the predominant role in the chicken photoreceptor circadian clockwork mechanism, including the regulation of NPAS2 expression.
C1 [Haque, Rashidul; Ali, Fatima G.; Biscoglia, Rebecca; Abey, Jane; Iuvone, P. Michael] Emory Univ, Sch Med, Dept Ophthalmol, Atlanta, GA 30322 USA.
[Haque, Rashidul; Ali, Fatima G.; Biscoglia, Rebecca; Abey, Jane; Iuvone, P. Michael] Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA.
[Weller, Joan; Klein, David] NICHHD, Sect Neuroendrocrinol, Dev Neurobiol Lab, Bethesda, MD 20892 USA.
RP Iuvone, PM (reprint author), Emory Univ, Sch Med, Dept Ophthalmol, 1365B Clifton Rd NE, Atlanta, GA 30322 USA.
EM miuvone@emory.edu
FU NIH [R01 EY04864, P30 EY06360]; Research to Prevent Blindness (RPB)
FX The authors thank Trisha Sengupta for technical assistance. This work
was supported by NIH grants R01 EY04864, P30 EY06360, and an
unrestricted departmental grant from Research to Prevent Blindness
(RPB). PMI is a recipient of an RPB Senior Scientific Investigator
Award.
NR 50
TC 14
Z9 18
U1 1
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD JUN
PY 2010
VL 113
IS 5
BP 1296
EP 1306
DI 10.1111/j.1471-4159.2010.06698.x
PG 11
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 591SG
UT WOS:000277323000020
PM 20345751
ER
PT J
AU Li, YZ
Tweedie, D
Mattson, MP
Holloway, HW
Greig, NH
AF Li, Yazhou
Tweedie, David
Mattson, Mark P.
Holloway, Harold W.
Greig, Nigel H.
TI Enhancing the GLP-1 receptor signaling pathway leads to proliferation
and neuroprotection in human neuroblastoma cells
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE 6-hydroxydopamine; exendin-4; glucagon-like peptide-1; neuroprotection;
oxidative stress; Parkinson's disease
ID GLUCAGON-LIKE PEPTIDE-1; ENDOPLASMIC-RETICULUM STRESS; OXIDATIVE STRESS;
ALZHEIMERS-DISEASE; HIPPOCAMPAL-NEURONS; PARKINSONS-DISEASE; RODENT
MODELS; ANIMAL-MODEL; BLOOD-BRAIN; BETA
AB P>Increasing evidence suggests that glucagon-like peptide-1 (GLP-1), an incretin hormone of current interest in type 2 diabetes, is neuroprotective in both cell culture and animal models. To characterize the neuroprotective properties of GLP-1 and associated underlying mechanisms, we over-expressed the GLP-1 receptor (GLP-1R) on human neuroblastoma SH-SY5Y cells to generate a neuronal culture system featuring enhanced GLP-1R signaling. In GLP-1R over-expressing SH-SY5Y (SH-hGLP-1R#9) cells, GLP-1 and the long-acting agonist exendin-4 stimulated cell proliferation and increased cell viability by 2-fold at 24 h at physiologically relevant concentrations. This GLP-1R-dependent action was mediated via the protein kinase A and phosphoinositide 3-kinase signaling pathways, with the MAPK pathway playing a minor role. GLP-1 and exendin-4 pretreatment dose-dependently protected SH-hGLP-1R#9 cells from hydrogen peroxide (H(2)O(2))- and 6-hydroxydopamine-induced cell death. This involved amelioration of elevated caspase 3 activity, down-regulation of pro-apoptotic Bax and up-regulation of anti-apoptotic Bcl-2 protein. In the presence of 6-hydroxydopamine, GLP-1's ability to lower caspse-3 activity was abolished with the phosphoinositide 3-kinase inhibitor, LY2940002, and partly reduced with the protein kinase A inhibitor, H89. Hence, GLP-1R mediated neurotrophic and anti-apoptotic actions co-contribute to the neuroprotective property of GLP-1 in neuronal cell cultures, and reinforce the potential therapeutic value of GLP-1R agonists in neurodegenerative disorders involving oxidative stress.
C1 [Li, Yazhou] NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program,Biomed Res Ctr,NIH, Baltimore, MD 21224 USA.
[Tweedie, David] MedStar Res Inst, Baltimore, MD USA.
RP Li, YZ (reprint author), NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program,Biomed Res Ctr,NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM liyaz@grc.nia.nih.gov
RI Mattson, Mark/F-6038-2012
FU National Institute on Aging, National Institutes of Health; MedStar
Research Institute
FX This research was supported by the Intramural Research Program of the
National Institute on Aging, National Institutes of Health. A portion of
that support was through a R & D contract with MedStar Research
Institute. The authors declare no conflicts of interest.
NR 31
TC 58
Z9 63
U1 0
U2 11
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD JUN
PY 2010
VL 113
IS 6
BP 1621
EP 1631
DI 10.1111/j.1471-4159.2010.06731.x
PG 11
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 604WT
UT WOS:000278309900024
PM 20374430
ER
PT J
AU Fox, E
Jayaprakash, N
Pham, TH
Rowley, A
McCully, CL
Pucino, F
Goldbach-Mansky, R
AF Fox, Elizabeth
Jayaprakash, Nalini
Pham, Tuyet-Hang
Rowley, Ayana
McCully, Cynthia L.
Pucino, Frank
Goldbach-Mansky, Raphaela
TI The serum and cerebrospinal fluid pharmacokinetics of anakinra after
intravenous administration to non-human primates
SO JOURNAL OF NEUROIMMUNOLOGY
LA English
DT Article
DE IL-1Ra; IL-1; Anakinra; Pharmacokinetics; NOMID
ID INTERLEUKIN-1 RECEPTOR ANTAGONIST; BLOOD-BRAIN-BARRIER; MULTISYSTEM
INFLAMMATORY DISEASE; RHESUS-MONKEY; PLASMA
AB Anakinra improves the central nervous system manifestations of neonatal-onset multisystem inflammatory disease, which is mediated by IL-1 beta oversecretion. The cerebrospinal fluid (CSF) penetration of the IL-1 receptor antagonist anakinra was studied in rhesus monkeys after intravenous doses of 3 and 10 mg/kg. Drug exposure (area under concentration-time curve) in CSF was 0.28% of that in serum. The average CSF concentration at 3 mg/kg was 1.8 ng/mL, which is 30-fold higher than endogenous CSF levels of IL-1Ra. The CSF penetration was not dose-dependent, indicating that the CSF penetration was not saturated in the 3 to 10 mg/kg dose range. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Fox, Elizabeth] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA.
[Jayaprakash, Nalini; McCully, Cynthia L.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Pham, Tuyet-Hang; Rowley, Ayana; Pucino, Frank; Goldbach-Mansky, Raphaela] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Pucino, Frank] US FDA, Ctr Drug Evaluat & Res, DHHS, Silver Spring, MD USA.
RP Fox, E (reprint author), Childrens Hosp Philadelphia, Div Oncol, CTRB 4016,3501 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM Foxe@email.chop.edu
FU Intramural NIH HHS [Z99 AR999999, Z01 AR041138-06, Z01 AR041138-05, ZIA
AR041138-07]
NR 20
TC 10
Z9 10
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-5728
J9 J NEUROIMMUNOL
JI J. Neuroimmunol.
PD JUN
PY 2010
VL 223
IS 1-2
BP 138
EP 140
DI 10.1016/j.jneuroim.2010.03.022
PG 3
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 627SG
UT WOS:000280062100021
PM 20421138
ER
PT J
AU Swett, BA
Contreras-Vidal, JL
Birn, R
Braun, A
AF Swett, Bruce A.
Contreras-Vidal, Jose L.
Birn, Rasmus
Braun, Allen
TI Neural Substrates of Graphomotor Sequence Learning: A Combined fMRI and
Kinematic Study
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
ID ANTERIOR CINGULATE CORTEX; FINE MOTOR CONTROL; PARKINSONS-DISEASE;
VISUOMOTOR TRANSFORMATIONS; BRAIN ACTIVATION; IMPLICIT; PERFORMANCE;
MECHANISMS; NETWORKS; MOVEMENT
AB Swett BA, Contreras-Vidal JL, Birn R, Braun A. Neural substrates of graphomotor sequence learning: a combined fMRI and kinematic study. J Neurophysiol 103: 3366-3377, 2010. First published April 7, 2010; doi:10.1152/jn.00449.2009. The goal of this study was to characterize the dynamics and functional connectivity of brain networks associated with fast (short-term) learning of handwriting using functional magnetic resonance imaging. Participants (n = 12) performed a graphomotor sequence learning task (naive subjects learning to draw simple, 3-stroke Chinese word characters), which focused the learning process on the kinematic aspects of sequence learning instead of on the production of the line segments. Learning of the graphomotor sequence was demonstrated by a progressive improvement in movement smoothness as assessed by normalized jerk scores. Examination of the patterns of regional neural activity and functional connectivity during sequence learning demonstrated that cortical regions, which may support visuomotor mapping components of the task, were active prior to subcortical areas that may play a role in encoding and refining the novel sequences. Importantly, differences in the time course of recruitment of basal ganglia and cerebellar networks suggest distinct but integrated roles in the encoding and refining of the handwritten sequences. This implies multiple kinematic representations of graphomotor trajectories may be encoded at various spatiotemporal scales.
C1 [Swett, Bruce A.; Braun, Allen] Natl Inst Deafness & Other Commun Disorders, Language Sect, NIH, Bethesda, MD 20892 USA.
[Birn, Rasmus] NIMH, Sect Neurocircuitry, NIH, Bethesda, MD 20892 USA.
[Swett, Bruce A.; Contreras-Vidal, Jose L.] Univ Maryland, Dept Kinesiol, College Pk, MD 20742 USA.
[Contreras-Vidal, Jose L.] Univ Maryland, Bioengn Program, College Pk, MD 20742 USA.
[Swett, Bruce A.; Contreras-Vidal, Jose L.] Univ Maryland, Neurosci & Cognit Sci Program, College Pk, MD 20742 USA.
RP Braun, A (reprint author), Natl Inst Deafness & Other Commun Disorders, Language Sect, NIH, Bldg 10,Rm 8S235A, Bethesda, MD 20892 USA.
EM brauna@nidcd.nih.gov
RI Contreras-Vidal, Jose/E-7888-2011
NR 46
TC 11
Z9 11
U1 2
U2 8
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD JUN
PY 2010
VL 103
IS 6
BP 3366
EP 3377
DI 10.1152/jn.00449.2009
PG 12
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 607IM
UT WOS:000278493900036
PM 20375250
ER
PT J
AU Hinckley, CA
Wiesner, EP
Mentis, GZ
Titus, DJ
Ziskind-Conhaim, L
AF Hinckley, Christopher A.
Wiesner, Eric P.
Mentis, George Z.
Titus, David J.
Ziskind-Conhaim, Lea
TI Sensory Modulation of Locomotor-Like Membrane Oscillations in
Hb9-Expressing Interneurons
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
ID MOUSE SPINAL-CORD; CENTRAL PATTERN GENERATORS; PRIMARY AFFERENT
SYNAPSES; FICTIVE LOCOMOTION; NEONATAL-RAT; HB9 INTERNEURONS; REFLEX
PATHWAYS; SACROCAUDAL AFFERENTS; MUSCLE AFFERENTS; EXTENSOR MUSCLES
AB Hinckley CA, Wiesner EP, Mentis GZ, Titus DJ, Ziskind-Conhaim L. Sensory modulation of locomotor-like membrane oscillations in Hb9-expressing interneurons. J Neurophysiol 103: 3407-3423, 2010. First published April 14, 2010; doi:10.1152/jn.00996.2009. The central pattern generator can generate locomotor-like rhythmic activity in the spinal cord in the absence of descending and peripheral inputs, but the motor pattern is regulated by feedback from peripheral sensory inputs that adjust motor outputs to external stimuli. To elucidate the possible role of Hb9-expressing interneurons (Hb9 INs) in the locomotor circuitry, we investigated whether their induced oscillatory activity is modulated by low-threshold afferents in the isolated spinal cords of neonatal Hb9:eGFP transgenic mice. Low-intensity stimulation of segmental afferents generated short-latency, monosynaptic excitatory responses in 62% of Hb9 INs. These were associated with longer-latency (similar to 13 ms) excitatory postsynaptic currents that were evoked in all Hb9 INs, probably by slow conducting afferents that synapse directly onto them. Concomitant morphological analysis confirmed that afferent axons with immunoreactive expression of vesicular glutamate transporter-1 and parvalbumin, presumably from primary afferents, contacted somata and dendrites of all Hb9 INs. Most of the putative synaptic contacts were on distal dendrites that extended to an area with profuse afferent projections. We next examined whether low-threshold afferents in upper (flexor-related) and lower (extensor-related) lumbar segments altered the timing of neurochemically induced locomotor-like rhythms in Hb9 INs and motoneurons. Excitation of flexor-related afferents during the flexor phase delayed the onset of subsequent cycles in both Hb9 INs and segmental motoneurons while maintaining the phase relationship between them. The in-phase correlation between voltage oscillations in Hb9 INs and motor bursts also persisted during the two-to threefold increase in cycle period triggered by extensor-related afferents. Our findings that low-threshold, presumably muscle afferents, synapse directly onto these interneurons and perturb their induced locomotor-like membrane oscillations in a pattern that remains phase-locked with motor bursts support the hypothesis that Hb9 INs are part of the sensorimotor circuitry that regulates the pattern of locomotor rhythms in the isolated cord.
C1 [Hinckley, Christopher A.; Wiesner, Eric P.; Titus, David J.; Ziskind-Conhaim, Lea] Univ Wisconsin, Sch Med & Publ Hlth, Dept Physiol, Madison, WI 53706 USA.
[Hinckley, Christopher A.; Wiesner, Eric P.; Titus, David J.; Ziskind-Conhaim, Lea] Univ Wisconsin, Sch Med & Publ Hlth, Ctr Neurosci, Madison, WI 53706 USA.
[Mentis, George Z.] NINDS, Sect Dev Neurobiol, NIH, Bethesda, MD 20892 USA.
RP Ziskind-Conhaim, L (reprint author), Univ Wisconsin, Sch Med, Dept Physiol, 129 SMI,1300 Univ Ave, Madison, WI 53706 USA.
EM lconhaim@physiology.wisc.edu
OI Titus, David/0000-0001-7819-734X
FU National Institute of Neurological Disorders and Stroke (NINDS)
[NS-23808]; NINDS
FX This study was supported by National Institute of Neurological Disorders
and Stroke (NINDS) Grant NS-23808 to L. Ziskind-Conhaim and NINDS
intramural funds to G. Z. Mentis.
NR 73
TC 9
Z9 9
U1 0
U2 0
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD JUN
PY 2010
VL 103
IS 6
BP 3407
EP 3423
DI 10.1152/jn.00996.2009
PG 17
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 607IM
UT WOS:000278493900040
PM 20393069
ER
PT J
AU Robertson, K
Liner, J
Hakim, J
Sankale, JL
Grant, I
Letendre, S
Clifford, D
Diop, AG
Jaye, A
Kanmogne, G
Njamnshi, A
Langford, TD
Weyessa, TG
Wood, C
Banda, M
Hosseinipour, M
Sacktor, N
Nakasuja, N
Bangirana, P
Paul, R
Joska, J
Wong, J
Boivin, M
Holding, P
Kammerer, B
Van Rie, A
Ive, P
Nath, A
Lawler, K
Adebamowo, C
Royal, W
Joseph, J
AF Robertson, Kevin
Liner, Jeff
Hakim, James
Sankale, Jean-Louis
Grant, Igor
Letendre, Scott
Clifford, David
Diop, Amadou Gallo
Jaye, Assan
Kanmogne, Georgette
Njamnshi, Alfred
Langford, T. Dianne
Weyessa, Tufa Gemechu
Wood, Charles
Banda, Mwanza
Hosseinipour, Mina
Sacktor, Ned
Nakasuja, Noeline
Bangirana, Paul
Paul, Robert
Joska, John
Wong, Joseph
Boivin, Michael
Holding, Penny
Kammerer, Betsy
Van Rie, Annelies
Ive, Prudence
Nath, Avindra
Lawler, Kathy
Adebamowo, Clement
Royal, Walter, III
Joseph, Jeymohan
CA NeuroAIDS Africa Conference
TI NeuroAIDS in Africa
SO JOURNAL OF NEUROVIROLOGY
LA English
DT Review
DE HIV; neurodevelopment; neurology; neuropsychology; subtypes
ID RECONSTITUTION INFLAMMATORY SYNDROME; DISEASE PROGRESSION; UNINFECTED
INFANTS; GENETIC SUBTYPES; HIV-1 SUBTYPES; CHILDREN; NEURODEVELOPMENT;
SUSCEPTIBILITY; MANIFESTATIONS; RECOMBINANTS
AB In July 2009, the Center for Mental Health Research on AIDS at the National Institute of Mental Health organized and supported the meeting "NeuroAIDS in Africa." This meeting was held in Cape Town, South Africa, and was affiliated with the 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention. Presentations began with an overview of the epidemiology of HIV in sub-Saharan Africa, the molecular epidemiology of HIV, HIV-associated neurocognitive disorders (HANDs), and HAND treatment. These introductory talks were followed by presentations on HAND research and clinical care in Botswana, Cameroon, Ethiopia, The Gambia, Kenya, Malawi, Nigeria, Senegal, South Africa, Uganda, and Zambia. Topics discussed included best practices for assessing neurocognitive disorders, patterns of central nervous system (CNS) involvement in the region, subtype-associated risk for HAND, pediatric HIV assessments and neurodevelopment, HIV-associated CNS opportunistic infections and immune reconstitution syndrome, the evolving changes in treatment implementation, and various opportunities and strategies for NeuroAIDS research and capacity building in the region. Journal of NeuroVirology (2010) 16, 189-202.
C1 [Robertson, Kevin] Univ N Carolina, Dept Neurol, Chapel Hill, NC 27599 USA.
[Hakim, James] Univ Zimbabwe, Harare, Zimbabwe.
[Sankale, Jean-Louis] Globomics LLC, Decatur, GA USA.
[Grant, Igor] Univ Calif San Diego, La Jolla, CA 92093 USA.
[Letendre, Scott] Univ Calif San Diego, San Diego, CA 92103 USA.
[Clifford, David] Washington Univ, Sch Med, St Louis, MO USA.
[Diop, Amadou Gallo] Univ Dakar, Dakar, Senegal.
[Jaye, Assan] MRC Labs, Gambia Unit, Banjul, Gambia.
[Kanmogne, Georgette] Univ Nebraska Med Ctr, Omaha, NE USA.
[Njamnshi, Alfred] Univ Yaounde, Yaounde, Cameroon.
[Langford, T. Dianne] Temple Univ, Sch Med, Philadelphia, PA 19122 USA.
[Weyessa, Tufa Gemechu] Univ Addis Ababa, Addis Ababa, Ethiopia.
[Wood, Charles] Univ Nebraska, Nebraska Ctr Virol, Lincoln, NE USA.
[Banda, Mwanza] Univ Teaching Hosp, Lusaka, Zambia.
[Hosseinipour, Mina] UNC Project, Lilongwe, Malawi.
[Sacktor, Ned] Johns Hopkins Univ, Johns Hopkins Bayview Med Ctr, Baltimore, MD USA.
[Nakasuja, Noeline; Bangirana, Paul] Makerere Univ, Kampala, Uganda.
[Paul, Robert] Univ Missouri, St Louis, MO 63121 USA.
[Joska, John] Univ Cape Town, ZA-7925 Cape Town, South Africa.
[Wong, Joseph] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Boivin, Michael] Michigan State Univ, E Lansing, MI 48824 USA.
[Holding, Penny] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Kammerer, Betsy] Harvard Univ, Sch Med, Childrens Hosp Boston, Newton, MA USA.
[Van Rie, Annelies] Univ N Carolina, Chapel Hill, NC USA.
[Ive, Prudence] Helen Joseph Hosp, Clin HIV Res Unit, Gauteng, South Africa.
[Lawler, Kathy] Univ Penn, Philadelphia, PA 19104 USA.
[Adebamowo, Clement] Inst Human Virol, Off Strateg Informat & Res, Abuja, Nigeria.
[Royal, Walter, III] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Joseph, Jeymohan] NIMH, HIV Pathogenesis Neuropsychiat & Treatment Branch, Ctr Mental Hlth Res AIDS, NIH, Bethesda, MD 20892 USA.
RP Robertson, K (reprint author), Univ N Carolina, Dept Neurol, 170 Manning Dr, Chapel Hill, NC 27599 USA.
EM kevinr@neurology.unc.edu
RI Laughton, Barbara/Q-3496-2016; Van Rie, Annelies/C-2082-2017;
OI Laughton, Barbara/0000-0001-7260-7723; Van Rie,
Annelies/0000-0001-7666-3263; Adebamowo, Clement/0000-0002-6571-2880;
Bangirana, Paul/0000-0002-7136-0594
FU Medical Research Council [MC_UP_A900_1121, MC_UP_A900_1125]; NIMH NIH
HHS [R01 MH085602]; NINDS NIH HHS [R21 NS055639]
NR 25
TC 18
Z9 18
U1 4
U2 8
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA
SN 1355-0284
J9 J NEUROVIROL
JI J. Neurovirol.
PD JUN
PY 2010
VL 16
IS 3
BP 189
EP 202
DI 10.3109/13550284.2010.489597
PG 14
WC Neurosciences; Virology
SC Neurosciences & Neurology; Virology
GA 619AL
UT WOS:000279398200001
PM 20500018
ER
PT J
AU Nayak, TK
Garmestani, K
Baidoo, KE
Milenic, DE
Brechbiel, MW
AF Nayak, Tapan K.
Garmestani, Kayhan
Baidoo, Kwamena E.
Milenic, Diane E.
Brechbiel, Martin W.
TI Preparation, Biological Evaluation, and Pharmacokinetics of the Human
Anti-HER1 Monoclonal Antibody Panitumumab Labeled with Y-86 for
Quantitative PET of Carcinoma
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Article
DE PET; HER1; panitumumab; immunoPET; Y-86
ID GROWTH-FACTOR RECEPTOR; METASTATIC COLORECTAL-CANCER; SQUAMOUS-CELL
CARCINOMA; EGFR EXPRESSION; PRECLINICAL EVALUATION; ABX-EGF; CETUXIMAB;
BIODISTRIBUTION; DOSIMETRY; THERAPY
AB Panitumumab, a human monoclonal antibody that binds to the epidermal growth factor receptor (HER1), was approved by the Food and Drug Administration in 2006 for the treatment of patients with HER1-expressing carcinoma. In this article, we describe the preclinical development of Y-86-CHX-A ''-diethylene-triaminepentaacetic acid (DTPA)-panitumumab for quantitative PET of HER1-expressing carcinoma. Panitumumab was conjugated to CHX-A ''-DTPA and radiolabeled with Y-86. In vivo biodistribution, PET, blood clearance, area under the curve, area under the moment curve, and mean residence time were determined for mice bearing HER1-expressing human colorectal (LS-174T), prostate (PC-3), and epidermoid (A431) tumor xenografts. Receptor specificity was demonstrated by coinjection of 0.1 mg of panitumumab with the radioimmunoconjugate. Results: Y-86-CHX-A ''-DTPA-panitumumab was routinely prepared with a specific activity exceeding 2 GBq/mg. Biodistribution and PET studies demonstrated a high HER1-specific tumor uptake of the radioimmunoconjugate. In mice bearing LS-174T, PC-3, or A431 tumors, the tumor uptake at 3 d was 34.6 +/- 5.9, 22.1 +/- 1.9, and 22.7 +/- 1.7 percentage injected dose per gram (%ID/g), respectively. The corresponding tumor uptake in mice coinjected with 0.1 mg of panitumumab was 9.3 +/- 1.5, 8.8 +/- 0.9, and 10.0 +/- 1.3 %ID/g, respectively, at the same time point, demonstrating specific blockage of the receptor. Normal organ and tumor uptake quantified by PET was closely related (r(2) = 0.95) to values determined by biodistribution studies. The LS-174T tumor had the highest area under the curve (96.8 +/- 5.6 % ID.d.g(-1)) and area under the moment curve (262.5 +/- 14.9% ID.d(2).g(-1)); however, the tumor mean residence times were identical for all 3 tumors (2.7-2.8 d). Conclusion: This study demonstrates the potential of Y-86-CHX-A ''-DTPA-panitumumab for quantitative noninvasive PET of HER1-expressing tumors and represents the first step toward clinical translation.
C1 [Nayak, Tapan K.; Garmestani, Kayhan; Baidoo, Kwamena E.; Milenic, Diane E.; Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Brechbiel, MW (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, 10 Ctr Dr,Bldg 10,Rm B3B69, Bethesda, MD 20892 USA.
EM tapann@gmail.com; martinwb@mail.nih.gov
OI Nayak, Tapan/0000-0002-3706-6092
FU National Institutes of Health; National Cancer Institute; Center for
Cancer Research; U.S. Department of Health and Human Services
FX We thank Jurgen Seidel (National Cancer Institute, National Institutes
of Health) for technical input on the operations of the NIH ATLAS
small-animal PET scanner. This research was supported by the Intramural
Research Program of the National Institutes of Health, National Cancer
Institute, Center for Cancer Research, and the U.S. Department of Health
and Human Services.
NR 43
TC 33
Z9 35
U1 0
U2 8
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA
SN 0161-5505
J9 J NUCL MED
JI J. Nucl. Med.
PD JUN 1
PY 2010
VL 51
IS 6
BP 942
EP 950
DI 10.2967/jnumed.109.071290
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 601EC
UT WOS:000278040000022
PM 20484421
ER
PT J
AU Kein, MA
Nahin, RL
Messina, MJ
Rader, JI
Thompson, LU
Badger, TM
Dwyer, JT
Kim, YS
Pontzer, CH
Starke-Reed, PE
Weaver, CM
AF Kein, Marguerite A.
Nahin, Richard L.
Messina, Mark J.
Rader, Jeanne I.
Thompson, Lilian U.
Badger, Thomas M.
Dwyer, Johanna T.
Kim, Young S.
Pontzer, Carol H.
Starke-Reed, Pamela E.
Weaver, Connie M.
TI Guidance from an NIH Workshop on Designing, Implementing, and Reporting
Clinical Studies of Soy Interventions
SO JOURNAL OF NUTRITION
LA English
DT Article; Proceedings Paper
CT Workshop on Soy Protein/Isofavone Research - Challenges in Designing and
Evaluating Intervention Studies
CY JUL 28-29, 2009
CL Bethesda, MD
ID FOOD-FREQUENCY QUESTIONNAIRE; BREAST-CANCER RISK; PERFORMANCE
LIQUID-CHROMATOGRAPHY; SOYBEAN BETA-CONGLYCININ; MIDLIFE CHINESE WOMEN;
PROTEIN ISOLATE; ISOFLAVONE INTAKE; FEMALE RATS; US ADULTS; MULTIETHNIC
POPULATION
AB The NIH sponsored a scientific workshop, "Soy Protein/lsoflavone Research: Challenges in Designing and Evaluating Intervention Studies," July 28-29, 2009. The workshop goal was to provide guidance for the next generation of soy protein/isoflavone human research. Session topics included population exposure to soy; the variability of the human response to soy; product composition; methods, tools, and resources available to estimate exposure and protocol adherence; and analytical methods to assess soy in foods and supplements and analytes in biologic fluids and other tissues. The intent of the workshop was to address the quality of soy studies, not the efficacy or safety of soy. Prior NI H workshops and an evidence-based review questioned the quality of data from human soy studies. If clinical studies are pursued, investigators need to ensure that the experimental designs are optimal and the studies properly executed. The workshop participants identified methodological issues that may confound study results and interpretation. Scientifically sound and useful options for dealing with these issues were discussed. The resulting guidance is presented in this document with a brief rationale. The guidance is specific to soy clinical research and does not address nonsoy-related factors that should also be considered in designing and reporting clinical studies. This guidance may be used by investigators, journal editors, study sponsors, and protocol reviewers for a variety of purposes, including designing and implementing trials, reporting results, and interpreting published epidemiological and clinical studies. J. Nutr. 140: 1192S-1204S, 2010.
C1 [Nahin, Richard L.; Pontzer, Carol H.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
[Kim, Young S.] NCI, NIH, Bethesda, MD 20892 USA.
[Starke-Reed, Pamela E.] NIH, Div Nutr Res Coordinat, Bethesda, MD 20892 USA.
[Messina, Mark J.] Loma Linda Univ, Dept Nutr, Loma Linda, CA 92350 USA.
[Rader, Jeanne I.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
[Thompson, Lilian U.] Univ Toronto, Dept Nutr Sci, Toronto, ON M5S 3E2, Canada.
[Badger, Thomas M.] Univ Arkansas Med Sci, Dept Physiol & Biophys, Little Rock, AR 72202 USA.
[Weaver, Connie M.] Purdue Univ, Dept Foods & Nutr, W Lafayette, IN 47907 USA.
[Kein, Marguerite A.; Dwyer, Johanna T.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
RP Kein, MA (reprint author), NIH, Off Dietary Supplements, 6100 Execut Blvd,Room 3B01, Bethesda, MD 20892 USA.
EM kleinm@mail.nih.gov
OI Nahin, Richard/0000-0002-3682-4816; Dwyer, Johanna/0000-0002-0783-1769
NR 89
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
EI 1541-6100
J9 J NUTR
JI J. Nutr.
PD JUN
PY 2010
VL 140
IS 6
BP 1192S
EP 1204S
DI 10.3945/jn.110.121830
PG 13
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 597ZH
UT WOS:000277800700024
ER
PT J
AU Li, L
Chen, CYO
Aldini, G
Johnson, EJ
Rasmussen, H
Yoshida, Y
Niki, E
Blumberg, JB
Russell, RM
Yeum, KJ
AF Li, Lei
Chen, C. -Y. Oliver
Aldini, Giancarlo
Johnson, Elizabeth J.
Rasmussen, Helen
Yoshida, Yasukazu
Niki, Etsuo
Blumberg, Jeffrey B.
Russell, Robert M.
Yeum, Kyung-Jin
TI Supplementation with lutein or lutein plus green tea extracts does not
change oxidative stress in adequately nourished older adults
SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY
LA English
DT Article
DE Supplementation; Lipid peroxidation; Antioxidant status; Biological
system
ID TOTAL ANTIOXIDANT CAPACITY; VITAMIN-C; MACULAR DEGENERATION;
LIPID-PEROXIDATION; POSTMENOPAUSAL WOMEN; DIETARY CAROTENOIDS;
ALPHA-TOCOPHEROL; BETA-CAROTENE; FREE-RADICALS; HUMAN PLASMA
AB Epigallocatechin gallate, a major component of green tea polyphenols, protects against the oxidation of fat-soluble antioxidants including lutein. The current study determined the effect of a relatively high but a dietary achievable dose of lutein or lutein plus green tea extract on antioxidant status. Healthy subjects (50-70 years) were randomly assigned to one of two groups (n=20 in each group): (1) a lutein (12 mg/day) supplemented group or (2) a lutein (12 mg/day) plus green tea extract (200 mg/day) supplemented group. After 2 weeks of run-in period consuming less than two servings of lightly colored fruits and vegetables in their diet, each group was treated for 112 days while on their customary regular diets. Plasma carotenoids including lutein, tocopherols, flavanols and ascorbic acid were analyzed by HPLC-UVD and HPLC-electrochemical detector systems; total antioxidant capacity by fluorometry; lipid peroxidation by malondialdehyde using a HPLC system with a fluorescent detector and by total hydroxyoctadecadienoic acids using a GC/MS. Plasma lutein, total carotenoids and ascorbic acid concentrations of subjects in either the lutein group or the lutein plus green tea extract group were significantly increased (P<.05) at 4 weeks and throughout the 16-week study period. However, no significant changes from baseline in any biomarker of overall antioxidant activity or lipid peroxidation of the subjects were seen in either group. Our results indicate that an increase of antioxidant concentrations within a range that could readily be achieved in a healthful diet does not affect in vivo antioxidant status in normal healthy subjects when sufficient amounts of antioxidants already exist. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Li, Lei; Chen, C. -Y. Oliver; Johnson, Elizabeth J.; Rasmussen, Helen; Blumberg, Jeffrey B.; Yeum, Kyung-Jin] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[Li, Lei] Qingdao Univ, Coll Med, Qingdao 266021, Shandong, Peoples R China.
[Aldini, Giancarlo] Univ Milan, Ist Chim Farmaceut & Tossicol Pietro Pratesi, Fac Pharm, Milan, Italy.
[Yoshida, Yasukazu; Niki, Etsuo] Natl Inst Adv Ind Sci & Technol, Hlth Technol Res Ctr, Osaka, Japan.
[Russell, Robert M.] NIH, Off Director, Washington, DC USA.
RP Yeum, KJ (reprint author), Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
EM kyungjin.yeum@tufts.edu
RI YOSHIDA, YASUKAZU/H-8510-2016;
OI YOSHIDA, YASUKAZU/0000-0001-6034-2502; aldini,
giancarlo/0000-0002-2355-6744
FU National Eye Institute [R03EY015674]; US Department of Agriculture
[1950-51000-065-08S]
FX This research has been supported in part by the National Eye Institute
R03EY015674 and US Department of Agriculture, under Agreement
No.1950-51000-065-08S. Any opinions, findings, conclusion or
recommendations expressed in this publication are those of the authors
and do not necessarily reflect the view of the US Department of
Agriculture.
NR 49
TC 14
Z9 16
U1 0
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0955-2863
J9 J NUTR BIOCHEM
JI J. Nutr. Biochem.
PD JUN
PY 2010
VL 21
IS 6
BP 544
EP 549
DI 10.1016/j.jnutbio.2009.03.002
PG 6
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA 602OT
UT WOS:000278149400013
PM 19447020
ER
PT J
AU Barsevick, AM
Cleeland, CS
Manning, DC
O'Mara, AM
Reeve, BB
Scott, JA
Sloan, JA
AF Barsevick, Andrea M.
Cleeland, Charles S.
Manning, Donald C.
O'Mara, Ann M.
Reeve, Bryce B.
Scott, Jane A.
Sloan, Jeff A.
TI ASCPRO Recommendations for the Assessment of Fatigue as an Outcome in
Clinical Trials
SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT
LA English
DT Article
DE Cancer-related fatigue; self-report measures; clinical trials;
patient-reported outcomes
ID CANCER-RELATED FATIGUE; QUALITY-OF-LIFE; PATIENTS RECEIVING
CHEMOTHERAPY; PROPOSED DIAGNOSTIC-CRITERIA;
SYSTEMIC-LUPUS-ERYTHEMATOSUS; IMPORTANT DIFFERENCE;
RHEUMATOID-ARTHRITIS; SCREENING TOOL; HEALTH-STATUS; INSTRUMENTS
AB Context. Development of pharmacological and behavioral interventions for cancer-related fatigue (CRF) requires adequate measures of this symptom. A guidance document from the Food and Drug Administration offers criteria for the formulation and evaluation of patient-reported outcome measures used in clinical trials to support drug or device labeling claims.
Methods. An independent working group, ASCPRO (Assessing Symptoms of Cancer Using Patient-Reported Outcomes), has begun developing recommendations for the measurement of symptoms in oncology clinical trials. The recommendations of the Fatigue Task Force for measurement of CRF are presented here.
Results. There was consensus that CRF could be measured effectively in clinical trials as the sensation of fatigue or tiredness, impact of fatigue/tiredness on usual functioning, or as both sensation and impact. The ASCPRO Fatigue Task Force constructed a definition and conceptual model to guide the measurement of CRF. ASCPRO recommendations do not endorse a specific fatigue measure but clarify how to evaluate and implement fatigue assessments in clinical studies. The selection of a CRF measure should be tailored to the goals of the research. Measurement issues related to various research environments were also discussed.
Conclusions. There exist in the literature good measures of CRF for clinical trials, with strong evidence of clarity and comprehensibility to patients, content and construct validity, reliability, and sensitivity to change in conditions in which one would expect them to change (assay sensitivity), and sufficient evidence to establish guides for interpreting changes in scores. Direction for future research is discussed. J Pain Symptom Manage 2010;39:1086-1099. (C) 2010 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.
C1 [Barsevick, Andrea M.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Cleeland, Charles S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Manning, Donald C.] Shionogi USA Inc, Florham Pk, NJ USA.
[O'Mara, Ann M.; Reeve, Bryce B.] NCI, Bethesda, MD 20892 USA.
[Sloan, Jeff A.] Mayo Clin, Grad Sch Med, Rochester, MN USA.
[Scott, Jane A.] MAPI Values, Macclesfield, Cheshire, England.
RP Barsevick, AM (reprint author), Fox Chase Canc Ctr, 333 Cottman Ave, Philadelphia, PA 19111 USA.
EM andrea.barsevick@fccc.edu
OI Barsevick, Andrea/0000-0003-1829-6826
FU NINR NIH HHS [R01 NR004573, R01 NR004573-07]
NR 74
TC 49
Z9 50
U1 2
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0885-3924
J9 J PAIN SYMPTOM MANAG
JI J. Pain Symptom Manage.
PD JUN
PY 2010
VL 39
IS 6
BP 1086
EP 1099
DI 10.1016/j.jpainsymman.2010.02.006
PG 14
WC Health Care Sciences & Services; Medicine, General & Internal; Clinical
Neurology
SC Health Care Sciences & Services; General & Internal Medicine;
Neurosciences & Neurology
GA 619OM
UT WOS:000279439500013
PM 20538190
ER
PT J
AU Azevedo, MF
Xekouki, P
Keil, MF
Lange, E
Patronas, N
Stratakis, CA
AF Azevedo, Monalisa F.
Xekouki, Paraskevi
Keil, Meg F.
Lange, Eileen
Patronas, Nicholas
Stratakis, Constantine A.
TI An Unusual Presentation of Pediatric Cushing Disease: Recurrent
Corticotropinoma of the Posterior Pituitary Lobe
SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM
LA English
DT Article
DE Cushing disease; pituitary adenoma; microadenoma
ID INTERMEDIATE LOBE; ADENOMAS; EXPERIENCE; DIAGNOSIS; CHILDREN;
NEUROHYPOPHYSIS; MICROSURGERY; ADOLESCENTS; MANAGEMENT; TESTS
AB Cushing's syndrome (CS) is rare in childhood and adolescence and its diagnosis and work up are often challenging. We report the case of a 15-year-old girl with a recurrent corticotrophin (ACTH)-secreting adenoma, located in the posterior lobe of the pituitary gland. At the age of 11, she presented with classic CS symptoms; biochemical investigation was compatible with ACTH-dependent Cushing disease, although pituitary gland imaging did not show any tumor. Following transsphenoidal surgery (TSS), histopathological analysis identified an ACTH-secreting pituitary microadenoma arising from the posterior gland. The patient went into remission but 4 years later she presented with recurrent CS; this time, pituitary gland imaging showed a microadenoma located in the posterior lobe, which was resected after TSS. Posterior lobe pituitary adenomas are very rare and often hard to diagnose and treat; this is the first case of such a tumor causing recurrent Cushing's disease in a child.
C1 [Azevedo, Monalisa F.; Xekouki, Paraskevi; Keil, Meg F.; Lange, Eileen; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, PDEGEN, Sect Endocrinol & Genet, Bethesda, MD 20892 USA.
[Keil, Meg F.; Stratakis, Constantine A.] NIH, Interinst Pediat Endocrinol Triaining Program, Bethesda, MD 20892 USA.
[Patronas, Nicholas] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Azevedo, MF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, PDEGEN, Sect Endocrinol & Genet, Bethesda, MD 20892 USA.
FU NICHD, NIH, Bethesda, MD, U.S.A.
FX This work was supported by the Intramural Progarm, NICHD, NIH, Bethesda,
MD, 20892, U.S.A.
NR 24
TC 0
Z9 0
U1 0
U2 1
PU FREUND PUBLISHING HOUSE LTD
PI TEL AVIV
PA PO BOX 35010, TEL AVIV 61350, ISRAEL
SN 0334-018X
J9 J PEDIATR ENDOCR MET
JI J. Pediatr. Endocrinol. Metab.
PD JUN
PY 2010
VL 23
IS 6
BP 607
EP 612
DI 10.1515/jpem.2010.100
PG 6
WC Endocrinology & Metabolism; Pediatrics
SC Endocrinology & Metabolism; Pediatrics
GA 620OX
UT WOS:000279510300010
PM 20662335
ER
PT J
AU Henry, RK
Keil, MF
Stratakis, CA
Fechner, PY
AF Henry, Rohan K.
Keil, Margaret F.
Stratakis, Constantine A.
Fechner, Patricia Y.
TI Cushing's Syndrome Secondary to isolated Micronodular Adrenocotrical
Disease (iMAD) associated with Rapid Onset Weight Gain and Negative
Abdominal MRI Findings in a 3 year old Male
SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM
LA English
DT Article
DE Cushing's syndrome; micronodular adrenocortical disease; Carney complex;
primary pigmented adrenocortical disease (PPNAD); hypercorticolism
ID NODULAR ADRENOCORTICAL DISEASE; URINARY FREE CORTISOL; DIAGNOSIS;
CHILDREN; ADOLESCENTS; FEATURES; GENETICS; TUMORS
AB Cushing's syndrome (CS) is uncommon in childhood. CS may be either dependent or independent of adrenocorticotrophic hormone (ACTH). ACTH independent micronodular adrenocortical (MAD) disease may present in the second to third decade of life or between ages 2-3years. It may occur in isolation, or as a part of the Carney complex and it represents an elusive entity to diagnose. We present a 3 year 7 month old boy with isolated MAD (iMAD). Abdominal CT revealed prominent mildly lobulated anteromedial margin of adrenals with nodular appearance. Cardiac echo, thyroid and testicular ultrasounds performed as a work up for Carney complex were normal. Bilateral adrenalectomy confirmed MAD as the cause of CS. We present the history and identification of a unique case of iMAD.
C1 [Henry, Rohan K.; Fechner, Patricia Y.] Seattle Childrens Hosp, Seattle, WA USA.
[Keil, Margaret F.; Stratakis, Constantine A.] NICHHD, NIH, Bethesda, MD 20892 USA.
RP Fechner, PY (reprint author), Seattle Childrens Hosp, Seattle, WA USA.
EM patricia.fechner@seattlechildrens.org
FU Intramural NIH HHS [ZIA HD000642-12]
NR 27
TC 0
Z9 0
U1 0
U2 1
PU WALTER DE GRUYTER GMBH
PI BERLIN
PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY
SN 0334-018X
EI 2191-0251
J9 J PEDIATR ENDOCR MET
JI J. Pediatr. Endocrinol. Metab.
PD JUN
PY 2010
VL 23
IS 6
BP 613
EP 620
DI 10.1515/jpem.2010.101
PG 8
WC Endocrinology & Metabolism; Pediatrics
SC Endocrinology & Metabolism; Pediatrics
GA 620OX
UT WOS:000279510300011
PM 20662336
ER
PT J
AU Lodish, MB
Hsiao, HP
Serbis, A
Sinaii, N
Rothenbuhler, A
Keil, MF
Boikos, SA
Reynolds, JC
Stratakis, CA
AF Lodish, Maya B.
Hsiao, Hui-Pin
Serbis, Anastasios
Sinaii, Ninet
Rothenbuhler, Anya
Keil, Margaret F.
Boikos, Sosipatros A.
Reynolds, James C.
Stratakis, Constantine A.
TI Effects of Cushing Disease on Bone Mineral Density in a Pediatric
Population
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID GLUCOCORTICOID-INDUCED OSTEOPOROSIS; SURGICAL CURE; BODY-COMPOSITION;
GROWTH-HORMONE; LONG-TERM; MASS; CHILDREN; ADOLESCENTS; TURNOVER;
CHILDHOOD
AB Objective To evaluate bone mineral density (BMD) in children with Cushing disease before and after transphenoidal surgery (TSS).
Study design Hologic dual-energy x-ray absorptiometry (DXA) scans of 35 children with Cushing disease were analyzed retrospectively. Sixteen of the 35 patients had follow-up DXA scans performed 13 to 18 months after TSS. BMD and bone mineral apparent density (BMAD) for lumbar spine (LS) L1 to L4 and femoral neck (FN) were calculated.
Results Preoperatively, 38% and 23% of patients had osteopenia of the LS and FN, respectively. Both BMD and BMAD Z-scores of the LS were worse than those for the FN (-1.60 +/- 1.37 versus -1.04 +/- 1.19, P=.003), and (-1.90 +/- 1.49 versus-0.06 +/- 1.90, P<.001); postoperative improvement in BMD and BMAD were more pronounced in LS than in the FN (0.84 +/- 0.88 versus 0.15 +/- 0.62, P<.001; and 0.73 +/- 1.13 versus -0.26 +/- 1.21, P=.015). Pubertal stage, cortisol levels, and length of disease had no effect on BMD.
Conclusions In children with Cushing disease, vertebral BMD was more severely affected than femoral BMD and this effect was independent of degree or duration of hypercortisolism. BMD for the LS improved significantly after TSS; osteopenia in this group may be reversible. (J Pediatr 2010; 156: 1001-5).
C1 [Lodish, Maya B.; Hsiao, Hui-Pin; Serbis, Anastasios; Rothenbuhler, Anya; Keil, Margaret F.; Boikos, Sosipatros A.; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol Genet, Program Dev Endocrinol Genet, NIH, Bethesda, MD USA.
[Lodish, Maya B.; Stratakis, Constantine A.] NIH, Pediat Endocrinol Interinst Training Program, Bethesda, MD 20892 USA.
[Hsiao, Hui-Pin] Kaohsiung Med Univ, Kaohsiung Municipal HsiaoKang Hosp, Dept Pediat, Kaohsiung, Taiwan.
[Hsiao, Hui-Pin] Kaohsiung Med Univ, Coll Med, Kaohsiung, Taiwan.
[Sinaii, Ninet] NIH, Biostat & Clin Epidemiol Serv, Ctr Clin, Bethesda, MD 20892 USA.
[Reynolds, James C.] NIH, Dept Radiol, Div Nucl Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA.
RP Lodish, MB (reprint author), NICHD, NIH, CRC E Labs, Bldg 10,Room 1-3330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA.
EM lodishma@mail.nih.gov
FU US National Institutes of Health, National Institute of Child Health and
Human Development intramural project [Z01-HD-000642-04]
FX The authors have no financial relationships relevant to this article to
disclose. Supported by the US National Institutes of Health, National
Institute of Child Health and Human Development intramural project
(Z01-HD-000642-04) (C.S.). The authors declare no conflicts of interest.
NR 31
TC 13
Z9 14
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
EI 1097-6833
J9 J PEDIATR-US
JI J. Pediatr.
PD JUN
PY 2010
VL 156
IS 6
BP 1001
EP 1005
DI 10.1016/j.jpeds.2009.12.027
PG 5
WC Pediatrics
SC Pediatrics
GA 599TE
UT WOS:000277935400028
PM 20223476
ER
PT J
AU Higgins, RD
Baker, CJ
Raju, TNK
AF Higgins, R. D.
Baker, C. J.
Raju, T. N. K.
TI Executive summary of the workshop on infection in the high-risk infant
SO JOURNAL OF PERINATOLOGY
LA English
DT Editorial Material
DE infant; infection; newborn; sepsis
ID INTENSIVE-CARE-UNIT; BIRTH-WEIGHT INFANTS; RESISTANT
STAPHYLOCOCCUS-AUREUS; NEONATAL SEPSIS; BREAST-MILK; PREVENTION; AGE
AB For newborn infants in intensive care units, the morbidity and mortality from infection continues to be a major burden despite advances in neonatal care. Infants are at risk for early-onset, late-onset as well as hospital-acquired infections. Research studies are needed to optimize timely diagnosis and treatment, and develop patient-specific and system-wide strategies to prevent perinatal and neonatal infections. To address the knowledge gaps that preclude optimal, evidence-based care in this critical field, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) organized a workshop in August 2008. In this paper, we provide a summary of the discussions, focusing on major knowledge gaps, and prioritized suggestions for research in this area. Journal of Perinatology (2010) 30, 379-383; doi: 10.1038/jp.2009.199; published online 14 January 2010
C1 [Higgins, R. D.; Raju, T. N. K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Baker, C. J.] Baylor Coll Med, Sect Pediat Infect Dis, Houston, TX 77030 USA.
RP Higgins, RD (reprint author), NICHHD, Pregnancy & Perinatol Branch, 6100 Execut Blvd,Room 4B03,MSC 7510, Bethesda, MD 20892 USA.
EM higginsr@mail.nih.gov
FU Intramural NIH HHS [Z99 HD999999]
NR 18
TC 2
Z9 2
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0743-8346
J9 J PERINATOL
JI J. Perinatol.
PD JUN
PY 2010
VL 30
IS 6
BP 379
EP 383
DI 10.1038/jp.2009.199
PG 5
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 607ZO
UT WOS:000278546000003
PM 20072133
ER
PT J
AU McCrae, RR
Terracciano, A
De Fruyt, F
De Bolle, M
Gelfand, MJ
Costa, PT
Aguilar-Vafaie, ME
Ahn, CK
Ahn, HN
Alcalay, L
Allik, J
Avdeyeva, TV
Blatny, M
Bratko, D
Brunner-Sciarra, M
Cain, TR
Chittcharat, N
Crawford, JT
de Lima, MP
Fehr, R
Fickova, E
Gulgoz, S
Hoebiekova, M
Jussim, L
Klinkosz, W
Knezevic, G
de Figueroa, NL
Lockenhoff, CE
Martin, TA
Marusic, I
Mastor, KA
Nakazato, K
Nansubuga, F
Porrata, J
Puric, D
Realo, A
Reategui, N
Rolland, JP
Schmidt, V
Sekowski, A
Shakespeare-Finch, J
Shimonaka, Y
Simonetti, F
Siuta, J
Szmigielska, B
Vanno, V
Wang, L
Yik, M
AF McCrae, Robert R.
Terracciano, Antonio
De Fruyt, Filip
De Bolle, Marleen
Gelfand, Michele J.
Costa, Paul T., Jr.
Aguilar-Vafaie, Maria E.
Ahn, Chang-kyu
Ahn, Hyun-nie
Alcalay, Lidia
Allik, Jueri
Avdeyeva, Tatyana V.
Blatny, Marek
Bratko, Denis
Brunner-Sciarra, Marina
Cain, Thomas R.
Chittcharat, Niyada
Crawford, Jarret T.
de Lima, Margarida P.
Fehr, Ryan
Fickova, Emilia
Gulgoz, Sami
Hoebiekova, Martina
Jussim, Lee
Klinkosz, Waldemar
Knezevic, Goran
de Figueroa, Nora Leibovich
Loeckenhoff, Corinna E.
Martin, Thomas A.
Marusic, Iris
Mastor, Khairul Anwar
Nakazato, Katsuharu
Nansubuga, Florence
Porrata, Jose
Puric, Danka
Realo, Anu
Reategui, Norma
Rolland, Jean-Pierre
Schmidt, Vanina
Sekowski, Andrzej
Shakespeare-Finch, Jane
Shimonaka, Yoshiko
Simonetti, Franco
Siuta, Jerzy
Szmigielska, Barbara
Vanno, Vitanya
Wang, Lei
Yik, Michelle
CA 42 Collaborators Adolescent
TI The Validity and Structure of Culture-Level Personality Scores: Data
From Ratings of Young Adolescents
SO JOURNAL OF PERSONALITY
LA English
DT Article
ID NATIONAL CHARACTER STEREOTYPES; BIG 5; TRAITS; INVENTORY; PROFILES;
NEO-PI-3; PATTERNS; CHILDREN; GENDER; WARMTH
AB We examined properties of culture-level personality traits in ratings of targets (N=5,109) ages 12 to 17 in 24 cultures. Aggregate scores were generalizable across gender, age, and relationship groups and showed convergence with culture-level scores from previous studies of self-reports and observer ratings of adults, but they were unrelated to national character stereotypes. Trait profiles also showed cross-study agreement within most cultures, 8 of which had not previously been studied. Multidimensional scaling showed that Western and non-Western cultures clustered along a dimension related to Extraversion. A culture-level factor analysis replicated earlier findings of a broad Extraversion factor but generally resembled the factor structure found in individuals. Continued analysis of aggregate personality scores is warranted.
C1 [McCrae, Robert R.; Terracciano, Antonio; Costa, Paul T., Jr.] NIA, Bethesda, MD 20892 USA.
[De Fruyt, Filip; De Bolle, Marleen] Univ Ghent, Ghent, Belgium.
[Gelfand, Michele J.; Fehr, Ryan] Univ Maryland, College Pk, MD 20742 USA.
[Aguilar-Vafaie, Maria E.] Tarbiat & Modarres Univ, Tehran, Iran.
[Ahn, Chang-kyu] Pusan Natl Univ, Pusan, South Korea.
[Ahn, Hyun-nie] Ewha Womans Univ, Seoul, South Korea.
[Alcalay, Lidia; Simonetti, Franco] Pontificia Univ Catolica Chile, Santiago, Chile.
[Allik, Jueri; Realo, Anu] Univ Tartu, Tartu, Estonia.
[Avdeyeva, Tatyana V.] Univ St Thomas, Minneapolis, MN USA.
[Blatny, Marek; Hoebiekova, Martina] Acad Sci Czech Republic, Prague, Czech Republic.
[Bratko, Denis] Univ Zagreb, Zagreb, Croatia.
[Brunner-Sciarra, Marina; Reategui, Norma] Univ Peruana Cayetano Heredia, Lima, Peru.
[Cain, Thomas R.; Jussim, Lee] Rutgers State Univ, Camden, NJ USA.
[Chittcharat, Niyada] Srinakharinwirot Univ, Bangkok, Thailand.
[Crawford, Jarret T.] Coll New Jersey, Ewing, NJ USA.
[de Lima, Margarida P.] Univ Coimbra, Coimbra, Portugal.
[Fickova, Emilia] Slovak Acad Sci, Bratislava, Slovakia.
[Gulgoz, Sami] Koc Univ, Istanbul, Turkey.
[Klinkosz, Waldemar; Sekowski, Andrzej] John Paul II Catholic Univ Lublin, Lublin, Poland.
[Knezevic, Goran; Puric, Danka] Univ Belgrade, Belgrade, Serbia Monteneg.
[de Figueroa, Nora Leibovich; Schmidt, Vanina] Univ Buenos Aires, Buenos Aires, DF, Argentina.
[Loeckenhoff, Corinna E.] Cornell Univ, Ithaca, NY USA.
[Martin, Thomas A.] Susquehanna Univ, Selinsgrove, PA USA.
[Marusic, Iris] Inst Social Res, Zagreb, Croatia.
[Mastor, Khairul Anwar] Univ Kebangsaan Malaysia, Bangi, Malaysia.
[Nakazato, Katsuharu] Iwate Prefectural Univ, Takizawa, Iwate, Japan.
[Nansubuga, Florence] Makerere Univ, Kampala, Uganda.
[Rolland, Jean-Pierre] Univ Paris Ouest Nanterre La Def, Paris, France.
[Shakespeare-Finch, Jane] Queensland Univ Technol, Brisbane, Qld, Australia.
[Shimonaka, Yoshiko] Bunkyo Gakuin Univ, Tokyo, Japan.
[Siuta, Jerzy; Szmigielska, Barbara] Jagiellonian Univ, Krakow, Poland.
[Vanno, Vitanya] Srinakharinwirot Univ, Bangkok, Thailand.
[Wang, Lei] Peking Univ, Beijing, Peoples R China.
[Yik, Michelle] Hong Kong Univ Sci & Technol, Hong Kong, Hong Kong, Peoples R China.
RP McCrae, RR (reprint author), 809 Evesham Ave, Baltimore, MD 21212 USA.
EM RRMcCrae@gmail.com
RI De Fruyt, Filip/A-3083-2009; terracciano, antonio/B-1884-2008; Blatny,
Marek/H-4293-2014; Allik, Juri/D-5609-2009; Wang, Lei/D-2501-2016;
Realo, Anu/M-9524-2016; Sekowski, Andrzej/O-7807-2016;
OI Blatny, Marek/0000-0001-9831-0637; Allik, Juri/0000-0002-8358-4747;
Wang, Lei/0000-0002-6156-9028; Costa, Paul/0000-0003-4375-1712;
Loeckenhoff, Corinna/0000-0003-1605-1323
FU Intramural NIH HHS [Z99 AG999999, ZIA AG000180-26, ZIA AG000180-25]
NR 43
TC 12
Z9 13
U1 3
U2 31
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3506
EI 1467-6494
J9 J PERS
JI J. Pers.
PD JUN
PY 2010
VL 78
IS 3
BP 815
EP 838
DI 10.1111/j.1467-6494.2010.00634.x
PG 24
WC Psychology, Social
SC Psychology
GA 595PQ
UT WOS:000277625000001
PM 20573127
ER
PT J
AU Khurana, S
Shah, N
Cheng, KR
Shiu, B
Samimi, R
Belo, A
Shant, J
Drachenberg, C
Wess, J
Raufman, JP
AF Khurana, Sandeep
Shah, Nirish
Cheng, Kunrong
Shiu, Brian
Samimi, Roxana
Belo, Angelica
Shant, Jasleen
Drachenberg, Cinthia
Wess, Juergen
Raufman, Jean-Pierre
TI Scopolamine Treatment and Muscarinic Receptor Subtype-3 Gene Ablation
Augment Azoxymethane-Induced Murine Liver Injury
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID HEPATIC STEM-CELLS; ACETYLCHOLINE-RECEPTOR; PROGENITOR CELLS;
PARTIAL-HEPATECTOMY; NERVOUS-SYSTEM; MOUSE-LIVER; RAT-LIVER; MICE;
REGENERATION; APOPTOSIS
AB Previous work suggests that vagus nerve disruption reduces hepatocyte and oval cell expansion after liver injury. The role of postneuronal receptor activation in response to liver injury has not been ascertained. We investigated the actions of scopolamine, a nonselective muscarinic receptor antagonist, and specific genetic ablation of a key cholinergic receptor, muscarinic subtype-3 (Chrm3), on azoxymethane (AOM)-induced liver injury in mice. Animal weights and survival were measured as was liver injury using both gross and microscopic examination. To assess hepatocyte proliferation and apoptosis, ductular hyperplasia, and oval cell expansion, we used morphometric analysis of 5-bromo-2'-deoxyuridine-, activated caspase-3-, hematoxylin and eosin-, cytokeratin-19-, and epithelial cell adhesion molecule-stained liver sections. Sirius red staining was used as a measure of collagen deposition and its association with oval cell reaction. In AOM-treated mice, both muscarinic receptor blockade with scopolamine and Chrm3 ablation attenuated hepatocyte proliferation and augmented gross liver nodularity, apoptosis, and fibrosis. Compared with control, scopolamine-treated and Chrm3(-/-) AOM-treated mice had augmented oval cell reaction with increased ductular hyperplasia and oval cell expansion. Oval cell reaction correlated robustly with liver fibrosis. No liver injury was observed in scopolamine-treated and Chrm3(-/-) mice that were not treated with AOM. Only AOM-treated Chrm3(-/-) mice developed ascites and had reduced survival compared with AOM-treated wild-type controls. In AOM-induced liver injury, inhibiting postneuronal cholinergic muscarinic receptor activation with either scopolamine treatment or Chrm3 gene ablation results in prominent oval cell reaction. We conclude that Chrm3 plays a critical role in the liver injury response by modulating hepatocyte proliferation and apoptosis.
C1 [Khurana, Sandeep] Univ Maryland, Sch Nursing, Div Gastroenterol & Hepatol, Baltimore, MD 21201 USA.
[Khurana, Sandeep; Shah, Nirish; Cheng, Kunrong; Shiu, Brian; Samimi, Roxana; Belo, Angelica; Shant, Jasleen; Raufman, Jean-Pierre] VA Maryland Hlth Care Syst, Div Gastroenterol & Hepatol, Baltimore, MD USA.
[Drachenberg, Cinthia] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA.
[Wess, Juergen] NIDDK, NIH, Bethesda, MD USA.
RP Khurana, S (reprint author), Univ Maryland, Sch Nursing, Div Gastroenterol & Hepatol, 22 S Greene St,N3W50, Baltimore, MD 21201 USA.
EM skhurana@medicine.umaryland.edu
FU National Institutes of Health National Institute of Diabetes and
Digestive and Kidney Diseases [T32-DK067872, K08-DK081479]; National
Institutes of Health National Cancer Institute [CA107345, CA120407];
Office of Research and Development, Medical Research Service, Department
of Veterans Affairs; Baltimore Research and Education Foundation
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health National Institute of Diabetes and
Digestive and Kidney Diseases; the National Institutes of Health
National Cancer Institute [Grants CA107345, CA120407] (to J.-P.R.); the
National Institutes of Health National Institute of Diabetes and
Digestive and Kidney Diseases [Grant T32-DK067872] (to N.S.; principle
investigator J.-P.R.); the National Institutes of Health Institute of
Diabetes and Digestive and Kidney Diseases [Grant K08-DK081479] (to
S.K.); the Office of Research and Development, Medical Research Service,
Department of Veterans Affairs; and the Baltimore Research and Education
Foundation.
NR 39
TC 8
Z9 8
U1 2
U2 4
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD JUN
PY 2010
VL 333
IS 3
BP 639
EP 649
DI 10.1124/jpet.109.165118
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 612JZ
UT WOS:000278895800002
PM 20197374
ER
PT J
AU Zhang, F
Qian, L
Flood, PM
Shi, JS
Hong, JS
Gao, HM
AF Zhang, Feng
Qian, Li
Flood, Patrick M.
Shi, Jing-Shan
Hong, Jau-Shyong
Gao, Hui-Ming
TI Inhibition of I kappa B Kinase-beta Protects Dopamine Neurons Against
Lipopolysaccharide-Induced Neurotoxicity
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID PARKINSONS-DISEASE; MICROGLIAL CELLS; NADPH OXIDASE; NITRIC-OXIDE;
ACTIVATION; IKK; PATHWAY; ALPHA; INFLAMMATION; MPTP
AB Parkinson's disease (PD) is a progressive neurological disorder characterized by a selective loss of dopamine (DA) neurons in the substantia nigra (SN). Although current therapy can control symptoms of this disorder, there is no effective therapy available to halt its progression. Recently, neuroinflammation has been recognized as an important contributor to the pathogenesis of PD, and nuclear factor-kappa B (NF-kappa B) plays a key role in regulating neuroinflammation. Hence, the modulation of NF-kappa B pathway may have therapeutic potential for PD. Activation of NF-kappa B depends on the phosphorylation of its inhibitor, I kappa B, by the specific I kappa B kinase (IKK) subunit IKK-beta. Compound A (7-[2(cyclopropylmethoxy)-6-hydroxyphenyl]-5-[(3S)-3-piperidinyl]-1, 4-dihydro-2H-pyrido[2,3-d][1,3]oxazin-2-one hydrochloride), a potent and selective inhibitor of IKK-beta, has recently been reported to provide cardioprotection through specific suppression of NF-kappa B signaling. The present study, for the first time, elucidates neuroprotective effects of compound A. Daily subcutaneous injection of compound A (1 mg/kg) for 7 days inhibited the activation of microglia induced by nigral stereotaxic injection of lipopolysaccharide (LPS) and significantly attenuated LPS-induced loss of DA neurons in the SN. In vitro mechanistic studies revealed that neuroprotective effects of compound A were mediated by 1) suppressing the activity of microglial NADPH oxidase and decreasing the production of reactive oxygen species, and 2) inhibiting NF-kappa B-mediated gene transcription of various proinflammatory mediators in microglia via IKK-beta suppression. These findings indicate that compound A afforded potent neuroprotection against LPS-induced neurodegeneration through selective inhibition of NF-kappa B activation and may be of potential benefit in the treatment of PD.
C1 [Zhang, Feng; Qian, Li; Hong, Jau-Shyong; Gao, Hui-Ming] NIEHS, Neuropharmacol Sect, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
[Zhang, Feng; Shi, Jing-Shan] Shanghai Univ Tradit Chinese Med, Shanghai, Peoples R China.
[Qian, Li; Flood, Patrick M.] Univ N Carolina, Comprehens Ctr Inflammatory Disorders, Chapel Hill, NC USA.
[Zhang, Feng; Shi, Jing-Shan] Zunyi Med Coll, Dept Pharmacol, Zunyi, Peoples R China.
[Zhang, Feng; Shi, Jing-Shan] Zunyi Med Coll, Key Lab Basic Pharmacol Guizhou, Zunyi, Peoples R China.
RP Gao, HM (reprint author), NIEHS, Neuropharmacol Sect, Lab Toxicol & Pharmacol, NIH, POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM gao2@niehs.nih.gov
RI gao, huiming/C-8454-2012
FU Michael J. Fox Foundation; National Institutes of Health National
Institute of Environmental Health Sciences
FX This work was supported by The Michael J. Fox Foundation for Parkinson's
Research and the Intramural Research Program of the National Institutes
of Health National Institute of Environmental Health Sciences.
NR 35
TC 34
Z9 38
U1 0
U2 8
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD JUN
PY 2010
VL 333
IS 3
BP 822
EP 833
DI 10.1124/jpet.110.165829
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 612JZ
UT WOS:000278895800021
PM 20190013
ER
PT J
AU Mason, CW
Hassan, HE
Kim, KP
Cao, JJ
Eddington, ND
Newman, AH
Voulalas, PJ
AF Mason, Clifford W.
Hassan, Hazem E.
Kim, Kang-Pil
Cao, Jianjing
Eddington, Natalie D.
Newman, Amy Hauck
Voulalas, Pamela J.
TI Characterization of the Transport, Metabolism, and Pharmacokinetics of
the Dopamine D3 Receptor-Selective Fluorenyl- and 2-Pyridylphenyl Amides
Developed for Treatment of Psychostimulant Abuse
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID FUNCTIONALIZED LINKING CHAINS; DRUG-SEEKING BEHAVIOR; D-3 RECEPTOR;
IN-VITRO; POPULATION PHARMACOKINETICS; INDUCED REINSTATEMENT;
BENZTROPINE ANALOGS; THERAPEUTIC AGENTS; ANIMAL-MODELS; RATS
AB The recent discovery of novel high-affinity and selective dopamine D3 receptor (DA D3R) antagonists and partial agonists has provided tools with which to further elucidate the role DA D3R plays in substance abuse. The present study was conducted to evaluate the transport, metabolism, pharmacokinetics, and brain uptake of the DA D3R-selective fluorenyl amides, NGB 2904 [N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)-9H-fluorene-2-carboxamide]fumarate) and JJC 4-077 [N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3-hydroxybutyl)-9H-fluorene-2-carboxamide hydrochloride], and the 2-pyridylphenyl amides, CJB 090 [N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)-4-(pyridine-2-yl)benzamide hydrochloride] and PG 01037 [N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-trans-but-2-enyl)-4-(pyridine-2-yl)benzamide hydrochloride], all of which have been studied in animal models of psychostimulant abuse. Additional screening with a panel of human and rat Supersomes was performed for NGB 2904 and PG 01037. Drug-stimulated ATPase activation assays and bidirectional transport and efflux assays were used to test for substrate specificity of NGB 2904 and PG 01037 for human and rat efflux transporters. All compounds exhibited moderate elimination half-lives, ranging from 1.49 to 3.27 h, and large volumes of distribution (5.95-14.19 l/kg). The brain-to-plasma ratios ranged from 2.93 to 11.81 and were higher than those previously reported for cocaine. Brain exposure levels of NGB 2904 and PG 01037 were significantly reduced after intraperitoneal administration compared with intravenous administration. The metabolism of these compounds was mediated primarily by CYP3A subfamilies. PG 01037 was a P-glycoprotein-transported substrate. Higher doses of these compounds are often required for in vivo action, suggesting decreased bioavailability via extravascular administration that may be attributed to high drug efflux and hepatic metabolism. These studies provide important preclinical information for optimization of next-generation D3R selective agents for the treatment of drug addiction.
C1 [Mason, Clifford W.; Hassan, Hazem E.; Kim, Kang-Pil; Eddington, Natalie D.; Voulalas, Pamela J.] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Pharmacokinet Biopharmaceut Lab, Baltimore, MD 21201 USA.
[Hassan, Hazem E.] Helwan Univ, Fac Pharm, Dept Pharmaceut & Ind Pharm, Helwan, Egypt.
[Cao, Jianjing; Newman, Amy Hauck] NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD USA.
RP Voulalas, PJ (reprint author), Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Pharmacokinet Biopharmaceut Lab, 20 Penn St,HSFII-559, Baltimore, MD 21201 USA.
EM pvoulala@rx.umaryland.edu
FU National Institutes of Health National Institute of Drug Abuse
[R01-DA1671503]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health National Institute of Drug Abuse [Grant
R01-DA1671503].
NR 36
TC 14
Z9 14
U1 1
U2 5
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD JUN
PY 2010
VL 333
IS 3
BP 854
EP 864
DI 10.1124/jpet.109.165084
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 612JZ
UT WOS:000278895800024
PM 20228156
ER
PT J
AU Zhou, SY
Mamdani, M
Qanud, K
Shen, JB
Pappano, AJ
Kumar, TS
Jacobson, KA
Hintze, T
Recchia, FA
Liang, BT
AF Zhou, Si-Yuan
Mamdani, Mohammed
Qanud, Khaled
Shen, Jian-Bing
Pappano, Achilles J.
Kumar, T. Santhosh
Jacobson, Kenneth A.
Hintze, Thomas
Recchia, Fabio A.
Liang, Bruce T.
TI Treatment of Heart Failure by a Methanocarba Derivative of Adenosine
Monophosphate: Implication for a Role of Cardiac Purinergic P2X
Receptors
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID MYOCARDIAL-INFARCTION; OVEREXPRESSING CALSEQUESTRIN; TRANSGENIC
EXPRESSION; PRESSURE-OVERLOAD; PHOSPHOLIPASE-C; MICE; CARDIOMYOPATHY;
DYSFUNCTION; MYOCYTES; RESCUE
AB Evidence is accumulating to support a potentially important role for purinergic (P2X) receptors in heart failure (HF). We tested the hypothesis that a hydrolysis-resistant nucleotide analog with agonist activity at myocardial P2X receptors (P2XRs) improves the systolic HF phenotype in mouse and dog models. We developed a hydrolysis-resistant adenosine monophosphate derivative, (1'S,2R,3S,4'R,5'S)-4-(6-amino-2-chloro-9H-purin-9-yl)-1-[phosphoryloxymethyl] bicycle[3.1.0]hexane-2,3-diol) (MRS2339), with agonist activity at native cardiac P2XRs. Chronic MRS2339 infusion in postinfarct and calsequestrin (CSQ) mice with HF resulted in higher rates of pressure change (+dP/dt), left ventricle (LV)-developed pressure, and cardiac output in an in vitro working heart model. Heart function in vivo, as determined by echocardiography-derived fractional shortening, was also improved in MRS2339-infused mice. The beneficial effect of MRS2339 was dose-dependent and was identical to that produced by cardiac myocyte-specific overexpression of the P2X(4) receptor. The HF improvement was associated with the preservation of LV wall thickness in both systole and diastole in postinfarct and CSQ mice. In dogs with pacing-induced HF, MRS2339 infusion reduced left ventricular end-diastolic pressure, improved arterial oxygenation, and increased +dP/dt. MRS2339 treatment also decreased LV chamber size in mice and dogs with HF. In murine and canine models of systolic HF, in vivo administration of a P2X nucleotide agonist improved contractile function and cardiac performance. These actions were associated with preserved LV wall thickness and decreased LV remodeling. The data are consistent with a role of cardiac P2XRs in mediating the beneficial effect of this agonist.
C1 [Shen, Jian-Bing; Pappano, Achilles J.; Liang, Bruce T.] Univ Connecticut, Ctr Hlth, Pat & Jim Calhoun Cardiol Ctr, Farmington, CT 06030 USA.
[Kumar, T. Santhosh; Jacobson, Kenneth A.] NIDDKD, NIH, Bethesda, MD 20892 USA.
[Zhou, Si-Yuan; Mamdani, Mohammed; Qanud, Khaled; Hintze, Thomas; Recchia, Fabio A.] New York Med Coll, Dept Physiol, Valhalla, NY 10595 USA.
[Recchia, Fabio A.] Scuola Super Sant Anna, Pisa, Italy.
RP Liang, BT (reprint author), Univ Connecticut, Ctr Hlth, Pat & Jim Calhoun Cardiol Ctr, MC 3946,263 Farmington Ave, Farmington, CT 06030 USA.
EM bliang@uchc.edu
RI Recchia, Fabio/F-2315-2010; Jacobson, Kenneth/A-1530-2009; Qanud,
Khaled/F-2771-2015
OI Jacobson, Kenneth/0000-0001-8104-1493; Qanud, Khaled/0000-0003-2943-1245
FU National Institutes of Health National Heart Lung and Blood Institute
[R01-HL48225]; Ray Neag Distinguished Professorship; National Institutes
of Health National Institute of Diabetes and Digestive and Kidney
Diseases
FX This work was supported in part by the National Institutes of Health
National Heart Lung and Blood Institute [Grant R01-HL48225], a Ray Neag
Distinguished Professorship, and the Intramural Research Program of the
National Institutes of Health National Institute of Diabetes and
Digestive and Kidney Diseases.
NR 36
TC 11
Z9 12
U1 0
U2 1
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD JUN
PY 2010
VL 333
IS 3
BP 920
EP 928
DI 10.1124/jpet.109.164376
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 612JZ
UT WOS:000278895800031
PM 20200116
ER
PT J
AU Thanos, PK
Bermeo, C
Rubinstein, M
Suchland, KL
Wang, GJ
Grandy, DK
Volkow, ND
AF Thanos, P. K.
Bermeo, C.
Rubinstein, M.
Suchland, K. L.
Wang, G. J.
Grandy, D. K.
Volkow, N. D.
TI Conditioned place preference and locomotor activity in response to
methylphenidate, amphetamine and cocaine in mice lacking dopamine D4
receptors
SO JOURNAL OF PSYCHOPHARMACOLOGY
LA English
DT Article
DE addiction; environment; learning; novelty; psychostimulants; substance
abuse
ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY
DISORDER; D4 DRD4 GENE; D-4 RECEPTOR; C57BL/6J MICE; DRUG; RATS;
MECHANISMS; BRAIN; EXPRESSION
AB Methylphenidate (MP) and amphetamine (AMPH) are the most frequently prescribed medications for the treatment of attention-deficit/hyperactivity disorder (ADHD). Both drugs are believed to derive their therapeutic benefit by virtue of their dopamine (DA)-enhancing effects, yet an explanation for the observation that some patients with ADHD respond well to one medication but not to the other remains elusive. The dopaminergic effects of MP and AMPH are also thought to underlie their reinforcing properties and ultimately their abuse. Polymorphisms in the human gene that codes for the DA D4 receptor (D4R) have been repeatedly associated with ADHD and may correlate with the therapeutic as well as the reinforcing effects of responses to these psychostimulant medications. Conditioned place preference (CPP) for MP, AMPH and cocaine were evaluated in wild-type (WT) mice and their genetically engineered littermates, congenic on the C57Bl/6J background, that completely lack D4Rs (knockout or KO). In addition, the locomotor activity in these mice D4 receptor KO and WT mice showed CPP and increased locomotor activity differentially modulates the CPP responses to MP, AMPH and cocaine. While the D4R genotype affected CPP responses to MP (high dose only) and AMPH (low dose only) it had no effects on cocaine. Inasmuch as CPP is considered an indicator of sensitivity to reinforcing responses to drugs these data suggest a significant but limited role of D4Rs in modulating conditioning responses to MP and AMPH. In the locomotor test, D4 receptor KO mice displayed attenuated increases in AMPH-induced locomotor activity whereas responses to cocaine and MP did not differ. These results suggest distinct mechanisms for D4 receptor modulation of the reinforcing (perhaps via attenuating dopaminergic signalling) and locomotor properties of these stimulant drugs. Thus, individuals with D4 receptor polymorphisms might show enhanced reinforcing responses to MP and AMPH and attenuated locomotor response to AMPH.
C1 [Thanos, P. K.; Bermeo, C.; Wang, G. J.] Brookhaven Natl Lab, Dept Med, Behav Pharmacol & Neuroimaging Lab, Upton, NY 11973 USA.
[Thanos, P. K.; Volkow, N. D.] NIAAA, Lab Neuroimaging, Intramural Program, NIH, Bethesda, MD USA.
[Thanos, P. K.] Univ Buenos Aires, Dept Psychol, Buenos Aires, DF, Argentina.
[Suchland, K. L.; Grandy, D. K.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA.
RP Thanos, PK (reprint author), Brookhaven Natl Lab, Dept Med, Behav Pharmacol & Neuroimaging Lab, Upton, NY 11973 USA.
EM thanos@bnl.gov
FU NIMH [MH67497]; NIAAA [AA 11034, AA07574, AA07611]; U.S. Department of
Energy [DE-AC02]; DOE SULI
FX This work was supported by NIMH (MH67497 to DKG), the NIAAA Intramural
Research Program (AA 11034 & AA07574, AA07611) and by the U.S.
Department of Energy under contract DE-AC02. CB was partially funded by
the DOE SULI summer research program.
NR 69
TC 21
Z9 21
U1 0
U2 4
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0269-8811
J9 J PSYCHOPHARMACOL
JI J. Psychopharmacol.
PD JUN
PY 2010
VL 24
IS 6
BP 897
EP 904
DI 10.1177/0269881109102613
PG 8
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 601UB
UT WOS:000278089200013
PM 19282420
ER
PT J
AU Manuck, T
Branch, DW
Lai, YL
Sibai, B
Spong, CY
Wendel, G
Wenstrom, K
Samuels, P
Caritis, SN
Sorokin, Y
Miodovnik, M
O'sullivan, MJ
Conway, D
Wapner, RJ
AF Manuck, Tracy
Branch, D. Ware
Lai, Yinglei
Sibai, Baha
Spong, Catherine Y.
Wendel, George, Jr.
Wenstrom, Katharine
Samuels, Philip
Caritis, Steve N.
Sorokin, Yoram
Miodovnik, Menachem
O'sullivan, Mary J.
Conway, Deborah
Wapner, Ronald J.
CA Eunice Kennedy Shriver Natl Inst C
TI Antiphospholipid antibodies and pregnancy outcomes in women heterozygous
for Factor V Leiden
SO JOURNAL OF REPRODUCTIVE IMMUNOLOGY
LA English
DT Article
DE Antiphospholipid antibodies; Factor V Leiden; Preeclampsia; Small for
gestational age
ID GENERAL OBSTETRIC POPULATION; ANTICARDIOLIPIN ANTIBODIES; PREECLAMPSIA;
CLASSIFICATION; ASSOCIATION; PREVALENCE; RISK
AB Antiphospholipid antibodies are associated with a spectrum of pregnancy complications, including preeclampsia and small for gestational age (SGA) fetuses. We sought to assess anticardiolipin and anti-beta 2-glycoprotein I (anti-beta 2-GPI) IgG and IgM antibody prevalence and the relationship of these antibodies to pregnancy complications in women with the Factor V Leiden (FVL) mutation. The study comprised a secondary analysis of a multicenter, prospective observational study of FVL prevalence among 5188 asymptomatic pregnant women. A subset of 362 women (117 FVL heterozygotes, 245 matched controls) had serum collected at the time of the original study and underwent serum analysis for anticardiolipin and anti-beta 2-GPI IgG and IgM as a part of this analysis. The primary outcome was preeclampsia and/or SGA (<10%). The overall prevalence of anticardiolipin and anti-beta 2-GPI IgG and IgM antibodies was low and did not vary with FVL status. Forty-seven women (13.0%) developed preeclampsia and/or SGA. There were no differences in primary outcome rates between women with and without aPL antibodies, regardless of FVL mutation status. Among FVL carriers, the presence of antiphospholipid antibodies does not appear to contribute to adverse pregnancy outcome. (C)10 Elsevier Ireland Ltd. All rights reserved.
C1 [Manuck, Tracy; Branch, D. Ware] Univ Utah, Dept Obstet, Salt Lake City, UT 84132 USA.
[Manuck, Tracy; Branch, D. Ware] Univ Utah, Dept Gynecol, Salt Lake City, UT 84132 USA.
[Lai, Yinglei] George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA.
[Sibai, Baha] Univ Cincinnati, Dept Obstet, Cincinnati, OH 45267 USA.
[Sibai, Baha] Univ Cincinnati, Dept Gynecol, Cincinnati, OH 45267 USA.
[Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD 20852 USA.
[Wendel, George, Jr.] Univ Texas SW Med Ctr Dallas, Dept Obstet, Dallas, TX 75235 USA.
[Wendel, George, Jr.] Univ Texas SW Med Ctr Dallas, Dept Gynecol, Dallas, TX 75235 USA.
[Wenstrom, Katharine] Univ Alabama, Dept Obstet, Birmingham, AL 35249 USA.
[Wenstrom, Katharine] Univ Alabama, Dept Gynecol, Birmingham, AL 35249 USA.
[Samuels, Philip] Ohio State Univ, Dept Obstet, Columbus, OH 43210 USA.
[Samuels, Philip] Ohio State Univ, Dept Gynecol, Columbus, OH 43210 USA.
[Caritis, Steve N.] Univ Pittsburgh, Dept Obstet, Pittsburgh, PA 15213 USA.
[Caritis, Steve N.] Univ Pittsburgh, Dept Gynecol, Pittsburgh, PA 15213 USA.
[Sorokin, Yoram] Wayne State Univ, Dept Obstet, Detroit, MI 48201 USA.
[Sorokin, Yoram] Wayne State Univ, Dept Gynecol, Detroit, MI 48201 USA.
[Miodovnik, Menachem] Univ Tennessee, Dept Obstet, Memphis, TN 38103 USA.
[Miodovnik, Menachem] Univ Tennessee, Dept Gynecol, Memphis, TN 38103 USA.
[O'sullivan, Mary J.] Univ Miami, Dept Obstet, Miami, FL 33136 USA.
[O'sullivan, Mary J.] Univ Miami, Dept Gynecol, Miami, FL 33136 USA.
[Conway, Deborah] Univ Texas San Antonio, Dept Obstet, San Antonio, TX 78229 USA.
[Conway, Deborah] Univ Texas San Antonio, Dept Gynecol, San Antonio, TX 78229 USA.
[Wapner, Ronald J.] Thomas Jefferson Univ, Dept Obstet, Philadelphia, PA 19107 USA.
[Wapner, Ronald J.] Thomas Jefferson Univ, Dept Gynecol, Philadelphia, PA 19107 USA.
RP Manuck, T (reprint author), Univ Utah, Hlth Sci Ctr, Dept Obstet & Gynecol, 30 North 1900 East,Room 2B200, Salt Lake City, UT 84132 USA.
EM tracy.manuck@hsc.utah.edu
RI Samuels, Philip/E-4011-2011;
OI caritis, steve/0000-0002-2169-0712
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 Institute of Health's Office of Research on Women's Health
(ORWH); H.A.; Edna Benning Presidential Chair
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 Institute of Health's
Office of Research on Women's Health (ORWH) and its contents are solely
the responsibility of the authors and do not necessarily represent the
official view of NICHD or ORWH.; This study was also supported in part
by funding of the H.A. and Edna Benning Presidential Chair (DWB).
NR 21
TC 2
Z9 2
U1 0
U2 2
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0165-0378
J9 J REPROD IMMUNOL
JI J. Reprod. Immunol.
PD JUN
PY 2010
VL 85
IS 2
BP 180
EP 185
DI 10.1016/j.jri.2010.03.007
PG 6
WC Immunology; Reproductive Biology
SC Immunology; Reproductive Biology
GA 625IL
UT WOS:000279888600008
PM 20439118
ER
PT J
AU Shaw, TH
Matthews, G
Warm, JS
Finomore, VS
Silverman, L
Costa, PT
AF Shaw, Tyler H.
Matthews, Gerald
Warm, Joel S.
Finomore, Victor S.
Silverman, Leanne
Costa, Paul T., Jr.
TI Individual differences in vigilance: Personality, ability and states of
stress
SO JOURNAL OF RESEARCH IN PERSONALITY
LA English
DT Article
DE Vigilance; Sustained attention; Five Factor Model; Mood; Ability;
Stress; Extraversion; Attentional resources
ID COGNITIVE FAILURES QUESTIONNAIRE; VISUAL SUSTAINED ATTENTION;
WORKING-MEMORY CAPACITY; BOREDOM PRONENESS; RESOURCE AVAILABILITY;
SENSITIVITY DECREMENT; ADHD SYMPTOMATOLOGY; YAQ-I; PERFORMANCE; TASK
AB Vigilance is notoriously hard to predict from personality measures. This study adopted a new multivariate approach based on attentional resource theory. Measures were taken of the Five Factor Model (FFM), more narrowly-defined 'cognitive-energetic' traits, cognitive ability and stress and coping scales. Participants (210) performed one of two related high-workload visual vigilance tasks. Results showed that personality traits were weak predictors of correct detection rate, although extraversion was negatively correlated with performance. Ability, subjective task engagement and coping scales were more strongly associated with vigilance. However, both the FFM and cognitive-energetic factors related to subjective states experienced during performance. Data support multivariate approaches to the prediction of vigilance based on attentional resource theory. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Matthews, Gerald] Univ Cincinnati, Dept Psychol, Cincinnati, OH 45221 USA.
[Shaw, Tyler H.] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA.
[Warm, Joel S.; Finomore, Victor S.] USAF, Res Lab, Wright Patterson AFB, OH 45433 USA.
[Silverman, Leanne; Costa, Paul T., Jr.] NIA, Lab Personal & Cognit, Bethesda, MD 20892 USA.
RP Matthews, G (reprint author), Univ Cincinnati, Dept Psychol, Cincinnati, OH 45221 USA.
EM Gerald.Matthews@uc.edu
OI Costa, Paul/0000-0003-4375-1712
NR 86
TC 22
Z9 23
U1 1
U2 24
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0092-6566
J9 J RES PERS
JI J. Res. Pers.
PD JUN
PY 2010
VL 44
IS 3
BP 297
EP 308
DI 10.1016/j.jrp.2010.02.007
PG 12
WC Psychology, Social
SC Psychology
GA 615RG
UT WOS:000279153000001
ER
PT J
AU Sutin, AR
Terracciano, A
Ferrucci, L
Costa, PT
AF Sutin, Angelina R.
Terracciano, Antonio
Ferrucci, Luigi
Costa, Paul T., Jr.
TI Teeth grinding: Is Emotional Stability related to bruxism?
SO JOURNAL OF RESEARCH IN PERSONALITY
LA English
DT Article
DE Emotional Stability; Bruxism; Teeth grinding; Personality; Anxiety
ID PERSONALITY-TRAITS; PHYSIOLOGY; BEHAVIOR
AB This study examines the association between personality traits and bruxism, the repetitive grinding or clenching of teeth. Community-dwelling participants (N = 470) had a comprehensive oral examination by a dentist and completed a dental history and personality questionnaires. Consistent with the literature on state anxiety and depression as antecedents of bruxism, Neuroticism-related traits were associated with self-reported teeth grinding. These traits were also associated with other oral complaints often associated with anxiety (jaw clicks, difficulty chewing food, and dry mouth), but not with more general oral health complaints (unhealthy gums, bleeding gums, and canker sores) or with dentist-assessed occlusal wear or tongue indentations. This study provides evidence for the association between Neuroticism and bruxism and other stress-related oral health symptoms. Published by Elsevier Inc.
C1 [Sutin, Angelina R.] NIA, Lab Personal & Cognit, NIH, DHHS, Baltimore, MD 21224 USA.
RP Sutin, AR (reprint author), NIA, Lab Personal & Cognit, NIH, DHHS, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM sutina@mail.nih.gov
RI terracciano, antonio/B-1884-2008;
OI Costa, Paul/0000-0003-4375-1712
FU Intramural NIH HHS [Z99 AG999999, ZIA AG000197-03, ZIA AG000197-04]
NR 16
TC 7
Z9 7
U1 0
U2 10
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0092-6566
J9 J RES PERS
JI J. Res. Pers.
PD JUN
PY 2010
VL 44
IS 3
BP 402
EP 405
DI 10.1016/j.jrp.2010.03.006
PG 4
WC Psychology, Social
SC Psychology
GA 615RG
UT WOS:000279153000013
PM 20835403
ER
PT J
AU Ward, MM
AF Ward, Michael M.
TI Access to Care and the Incidence of Endstage Renal Disease Due to
Systemic Lupus Erythematosus
SO JOURNAL OF RHEUMATOLOGY
LA English
DT Article
DE ACCESS TO CARE; SOCIOECONOMIC STATUS; ENDSTAGE RENAL DISEASE; SYSTEMIC
LUPUS ERYTHEMATOSUS
ID SOCIOECONOMIC-STATUS; RISK-FACTORS; NEPHRITIS; ASSOCIATION; RACE;
MORBIDITY; INSURANCE; FAILURE; COHORT; PERIOD
AB Objective. Persons with low socioeconomic status have an increased risk of endstage renal disease (ESRD) due to systemic lupus erythematosus (SLE), possibly because of limited access to care. We examined if the incidence of ESRD due to SLE was higher in geographic areas with poorer access to care.
Methods. In this population-based ecological study, we tested associations between the incidence of ESRD due to SLE and the proportion of hospitalizations with no insurance, Medicaid or managed care insurance, residence in a primary care-provider shortage area or rural area, and rate of hospitalizations for ambulatory care-sensitive conditions, by ZIP code in California in 1999-2004.
Results. The incidence of ESRD due to SLE was higher in ZIP codes with higher proportions of hospitalizations with no insurance (r = 0.22, p<0.0001) or Medicaid (r = 0.21, p<0.0001), and in ZIP codes with higher rates of hospitalizations for ambulatory care-sensitive conditions (r = 0.23, p<0.0001). In multivariate analyses, incidences were higher in ZIP codes with higher proportions of hospitalizations with Medicaid (p<0.0001) and higher rates of hospitalizations for ambulatory care-sensitive conditions (p = 0.06), independent of the socioeconomic status of the ZIP code residents.
Conclusion. The incidence of ESRD due to SLE is higher in areas with higher proportions of residents who have public insurance and higher rates of avoidable hospitalizations, suggesting that limited access to care may contribute to this complication of SLE. (First Release April 15 2010; J Rheumatol 2010;37:1158-63; doi:10.3899/jrheum.091199)
C1 [Ward, Michael M.] NIAMSD, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Ward, MM (reprint author), NIAMS, NIH, Bldg 10 CRC,Room 4-1339,10 Ctr Dr,MSC 1468, Bethesda, MD 20892 USA.
EM wardm1@mail.nih.gov
RI Dalla Zuanna, Teresa/G-3133-2015
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases,
National Institutes of Health, Bethesda, MD
FX Supported by the Intramural Research Program, National Institute of
Arthritis and Musculoskeletal and Skin Diseases, National Institutes of
Health, Bethesda, MD.
NR 32
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U1 0
U2 1
PU J RHEUMATOL PUBL CO
PI TORONTO
PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA
SN 0315-162X
J9 J RHEUMATOL
JI J. Rheumatol.
PD JUN
PY 2010
VL 37
IS 6
BP 1158
EP 1163
DI 10.3899/jrheum.091199
PG 6
WC Rheumatology
SC Rheumatology
GA 616FO
UT WOS:000279194600013
PM 20395647
ER
PT J
AU Li, QZ
Zheng, G
Liu, AY
Xiong, SF
Li, ZH
Yu, K
AF Li, Qizhai
Zheng, Gang
Liu, Aiyi
Xiong, Shifeng
Li, Zhaohai
Yu, Kai
TI The limiting bound of Efron's W-formula for hypothesis testing when a
nuisance parameter is present only under the alternative
SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE
LA English
DT Article
DE Hypothesis testing; Limiting bound; MAX; Nuisance parameter; Robustness;
W-formula
ID ROBUST-TESTS; TREND TEST; ASSOCIATION; MAXIMUM; TABLES; MODEL
AB When testing a hypothesis with a nuisance parameter present only under the alternative, the maximum of a test statistic over the nuisance parameter space has been proposed. Different upper bounds for the one-sided tail probabilities of the maximum tests were provided. Davies (1977. Biometrika 64, 247-254) studied the problem when the parameter space is an interval, while Efron (1997. Biometrika 84, 143-157) considered the problem with some finite points of the parameter space and obtained a W-formula. We study the limiting bound of Efron's W-formula when the number of points in the parameter space goes to infinity. The conditions under which the limiting bound of the W-formula is identical to that of Davies are given. The results are also extended to two-sided tests. Examples are used to illustrate the conditions, including case-control genetic association studies. Efficient calculations of upper bounds for the tail probability with finite points in the parameter space are described. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Li, Qizhai; Xiong, Shifeng] Chinese Acad Sci, Acad Math & Syst Sci, Key Lab Syst & Control, Beijing 100190, Peoples R China.
[Zheng, Gang] NHLBI, Off Biostat Res, Div Prevent & Populat Sci, Bethesda, MD 20892 USA.
[Liu, Aiyi] NICHHD, Biometry & Math Stat Branch, Bethesda, MD 20892 USA.
[Li, Zhaohai; Yu, Kai] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Li, Zhaohai] George Washington Univ, Dept Stat, Washington, DC 20052 USA.
RP Li, QZ (reprint author), Chinese Acad Sci, Acad Math & Syst Sci, Key Lab Syst & Control, Beijing 100190, Peoples R China.
EM liqz@amss.ac.cn
OI Liu, Aiyi/0000-0002-6618-5082
FU National Institutes of Health; National Young Science Foundation of
China [10901155]
FX We would like to thank an anonymous referee for the insightful comments
that improve the manuscript. We thank Dr. B.J.Stone for her valuable
help. The authors are supported by the Intramural Research Program of
the National Institutes of Health. Q. Li is partially supported by
National Young Science Foundation of China, no. 10901155.
NR 15
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U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-3758
J9 J STAT PLAN INFER
JI J. Stat. Plan. Infer.
PD JUN
PY 2010
VL 140
IS 6
BP 1610
EP 1617
DI 10.1016/j.jspi.2009.12.021
PG 8
WC Statistics & Probability
SC Mathematics
GA 566BT
UT WOS:000275345500022
ER
PT J
AU Williams, JM
Steinberg, ML
Zimmermann, MH
Gandhi, KK
Stipelman, B
Budsock, PD
Ziedonis, DM
AF Williams, Jill M.
Steinberg, Marc L.
Zimmermann, Mia Hanos
Gandhi, Kunal K.
Stipelman, Brooke
Budsock, Patricia Dooley
Ziedonis, Douglas M.
TI Comparison of two intensities of tobacco dependence counseling in
schizophrenia and schizoaffective disorder
SO JOURNAL OF SUBSTANCE ABUSE TREATMENT
LA English
DT Article
DE Smoking cessation; Mental illness; Nicotine; Behavioral therapy;
Randomized clinical trial
ID PLACEBO-CONTROLLED TRIAL; SMOKING-CESSATION; NICOTINE DEPENDENCE;
SUBSTANCE-ABUSE; MENTAL-HEALTH; SMOKERS; INTERVENTION; INDIVIDUALS;
PREVALENCE; BUPROPION
AB Compared to the general population, smokers with schizophrenia (SCZ) have reduced success in quitting smoking with usual approaches. This study tested two manualized behavioral counseling approaches-Treatment of Addiction to Nicotine in Schizophrenia (TANS) or Medication Management (MM)-for smokers who were motivated to quit. Individual counseling sessions were provided by mental health clinicians in mental health settings, along with nicotine patch. The two treatments varied in intensity and frequency of sessions. Eighty-seven subjects were randomized and attended at least one treatment session. Twenty-one percent (n = 18) of participants had continuous abstinence at 12 weeks after the target quit date, which was not significantly different between conditions (15.6% TANS vs. 26.2% MM, chi(2) = 1.50, p = .221). Smokers in both groups significantly reduced smoking as measured by cigarettes per day and expired carbon monoxide. Findings support that mental health clinicians can be trained to effectively help smokers with SCZ maintain tobacco abstinence. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Williams, Jill M.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Div Addict Psychiat, New Brunswick, NJ 08901 USA.
[Williams, Jill M.; Steinberg, Marc L.; Gandhi, Kunal K.] Univ Med & Dent New Jersey, Sch Publ Hlth, New Brunswick, NJ 08901 USA.
[Stipelman, Brooke] NCI, Bethesda, MD 20892 USA.
[Ziedonis, Douglas M.] Univ Massachusetts, Sch Med, Amherst, MA 01003 USA.
RP Williams, JM (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Div Addict Psychiat, 317 George St,Suite 105, New Brunswick, NJ 08901 USA.
EM jill.williams@umdnj.edu
OI Steinberg, Marc/0000-0001-8180-8682
FU NIDA NIH HHS [K23 DA018203, K23 DA014009, R01 DA015537-02S1, K23
DA014009-01, R01-DA015537, K23-DA 018203-02, R01 DA015537,
K-DA14009-01]; NIMH NIH HHS [R01 MH076672, R01-MH076672-01A1]
NR 42
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U1 1
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0740-5472
J9 J SUBST ABUSE TREAT
JI J. Subst. Abus. Treat.
PD JUN
PY 2010
VL 38
IS 4
BP 384
EP 393
DI 10.1016/j.jsat.2010.03.006
PG 10
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA 595AF
UT WOS:000277582400009
PM 20363089
ER
PT J
AU Ling, W
Jacobs, P
Hillhouse, M
Hasson, A
Thomas, C
Freese, T
Sparenborg, S
McCarty, D
Weiss, R
Saxon, A
Cohen, A
Straus, M
Brigham, G
Liu, D
McLaughlin, P
Tai, B
AF Ling, Walter
Jacobs, Petra
Hillhouse, Maureen
Hasson, Albert
Thomas, Christie
Freese, Thomas
Sparenborg, Steven
McCarty, Dennis
Weiss, Roger
Saxon, Andrew
Cohen, Allan
Straus, Michele
Brigham, Gregory
Liu, David
McLaughlin, Paul
Tai, Betty
TI From research to the real world: Buprenorphine in the decade of the
Clinical Trials Network
SO JOURNAL OF SUBSTANCE ABUSE TREATMENT
LA English
DT Article
DE Buprenorphine; CTN; Clinical Trials Network; Opioids; Opiate dependence;
Pharmacotherapy
ID SUBSTANCE-ABUSE TREATMENT; OPIOID DEPENDENCE; RANDOMIZED-TRIAL;
ADOPTION; DETOXIFICATION; NALOXONE; ADDICTION
AB The National Institute on Drug Abuse (NIDA) established the National Drug Abuse Treatment Clinical Trials Network (CTN) in 1999 to bring researchers and treatment providers together to develop a clinically relevant research agenda. Initial CTN efforts addressed the use of buprenorphine, a mu-opioid partial agonist, as treatment for opioid dependence. Strong evidence of buprenorphine's therapeutic efficacy was demonstrated in clinical trials involving several thousand opioid-dependent participants, and in 2002, the Food and Drug Administration approved buprenorphine for the treatment of opioid dependence. With the advent of a sublingual tablet containing both buprenorphine and naloxone to mitigate abuse and diversion (Suboxone), buprenorphine appeared poised to be the first-line treatment for opioid addiction. Notwithstanding its many attributes, certain implementation barriers remained to be addressed in CTN studies, and these efforts have brought a body of knowledge on buprenorphine to frontline clinicians. The purpose of this article is to review CTN-based buprenorphine research and related efforts to overcome challenges to the implementation of buprenorphine therapy in mainstream practice. Furthermore, this article explores current issues and future challenges that may require additional CTN efforts. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Ling, Walter; Hillhouse, Maureen; Hasson, Albert; Thomas, Christie; Freese, Thomas] Univ Calif Los Angeles, Los Angeles, CA 90024 USA.
[Jacobs, Petra; Sparenborg, Steven; Straus, Michele; Liu, David; Tai, Betty] Natl Inst Drug Abuse, NIDA CCTN, Ctr Clin Trials Network, Lexington, KY USA.
[McCarty, Dennis] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Weiss, Roger] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Saxon, Andrew] Vet Affairs Puget Sound Hlth Care Syst, Washington Reg Node, Washington, DC USA.
RP Hillhouse, M (reprint author), Univ Calif Los Angeles, Los Angeles, CA 90024 USA.
EM hillhous@ucla.edu
OI Brigham, Gregory/0000-0003-1150-4493
FU NIDA NIH HHS [U10 DA 13036, U10 DA 13045, U10 DA013045, U10 DA013045-09,
U10 DA013045-10, U10 DA015831, U10 DA13732, K24 DA022288, U10 DA15831,
K24DA022288]
NR 30
TC 22
Z9 22
U1 1
U2 7
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0740-5472
J9 J SUBST ABUSE TREAT
JI J. Subst. Abus. Treat.
PD JUN
PY 2010
VL 38
IS 4
SU 1
BP S53
EP S60
DI 10.1016/j.jsat.2010.01.009
PG 8
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA 595AG
UT WOS:000277582500006
PM 20307796
ER
PT J
AU Martino, S
Brigham, GS
Higgins, C
Gallon, S
Freese, TE
Albright, LM
Hulsey, EG
Krom, L
Storti, SA
Perl, H
Nugent, CD
Pintello, D
Condon, TP
AF Martino, Steve
Brigham, Gregory S.
Higgins, Christine
Gallon, Steve
Freese, Thomas E.
Albright, Lonnetta M.
Hulsey, Eric G.
Krom, Laurie
Storti, Susan A.
Perl, Harold
Nugent, Cathrine D.
Pintello, Denise
Condon, Timothy P.
TI Partnerships and pathways of dissemination: The National Institute on
Drug Abuse-Substance Abuse and Mental Health Services Administration
Blending Initiative in the Clinical Trials Network
SO JOURNAL OF SUBSTANCE ABUSE TREATMENT
LA English
DT Article
DE Dissemination; Technology transfer; Treatment adoption; Treatment
implementation; Buprenorphine; Motivational incentives; Motivational
interviewing; Evidence-based treatment; Substance abuse
ID MOTIVATIONAL ENHANCEMENT THERAPY; RANDOMIZED-TRIAL;
BUPRENORPHINE-NALOXONE; CONTINGENCY MANAGEMENT; TECHNOLOGY-TRANSFER;
TREATMENT ENGAGEMENT; TREATMENT PROVIDERS; TREATMENT PROGRAMS; ADOPTION;
INCENTIVES
AB Since 2001, the National Drug Abuse Treatment Clinical Trials Network (CTN) has worked to put the results of its trials into the hands of community treatment programs, in large part through its participation in the National Institute on Drug Abuse-Substance Abuse and Mental Health Services Administration Blending Initiative and its close involvement with the Center for Substance Abuse Treatment's Addiction Technology Transfer Centers. This article describes (a) the CTN's integral role in the Blending Initiative, (b) key partnerships and dissemination pathways through which the results of CTN trials are developed into blending products and then transferred to community treatment programs, and (c) three blending initiatives involving buprenorphine, motivational incentives, and motivational interviewing. The Blending Initiative has resulted in high utilization of its products, preparation of more than 200 regional trainers, widespread training of service providers in most U.S. States, Puerto Rico, and the U.S. Virgin Islands and movement toward the development of Web-based implementation supports and technical assistance. Implications for future directions of the Blending Initiative and opportunities for research are discussed. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Martino, Steve] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06519 USA.
[Brigham, Gregory S.] Maryhaven, Columbus, OH 43207 USA.
[Higgins, Christine] Johns Hopkins Sch Med, Dept Psychiat, Baltimore, MD 21218 USA.
[Gallon, Steve] NW Frontier Addict Technol Transfer Ctr, Salem, OR 97301 USA.
[Gallon, Steve] Oregon Hlth & Sci Univ, Dept Publ Hlth Prevent Med, Portland, OR 97239 USA.
[Freese, Thomas E.] Pacific SW Addict Technol Transfer Ctr, Los Angeles, CA 90025 USA.
[Freese, Thomas E.] Univ Calif Los Angeles, Integrated Subst Abuse Programs, Los Angeles, CA 90025 USA.
[Albright, Lonnetta M.] Great Lakes Addict Technol Transfer Ctr, Chicago, IL 60608 USA.
[Albright, Lonnetta M.] Univ Illinois, Jane Addams Coll Social Work, Chicago, IL 60608 USA.
[Hulsey, Eric G.] Inst Res Educ & Training Addict, Pittsburgh, PA 15219 USA.
[Hulsey, Eric G.] NE Addict Technol Transfer Ctr, Pittsburgh, PA 15219 USA.
[Krom, Laurie] ATTC Natl Off, Kansas City, MO 64110 USA.
[Storti, Susan A.] Synergy Enterprises Inc, Silver Spring, MD 20910 USA.
[Perl, Harold; Pintello, Denise; Condon, Timothy P.] Natl Inst Drug Abuse, Bethesda, MD 20892 USA.
[Nugent, Cathrine D.] Subst Abuse & Mental Hlth Serv Adm, Rockville, MD USA.
RP Martino, S (reprint author), Yale Univ, Sch Med, Dept Psychiat, VA Connecticut Healthcare Syst, 950 Campbell Ave,151-D, West Haven, CT 06516 USA.
EM steve.martino@yale.edu
OI Brigham, Gregory/0000-0003-1150-4493
FU CSAT SAMHSA HHS [5 UD1 TI-013594, 5UD1TI013404-08, 5UD1TI013593-08,
5UD1TI03592-0, 2UD1 TI 013424-06]; NIDA NIH HHS [U10-DA013711, U10
DA013716, U10 DA013045, 1K23DA021512, R01 DA023230-02, U10 DA013036, U10
DA013711, U10 DA013714, U10 DA013720, U10 DA013732, U10 DA13038,
U10-DA013035, U10-DA013038, U10-DA013710, U10-DA013716, U10-DA015831,
DA13045, U10-DA013043, U10-DA013046, U10-DA013727, U10-DA013034,
U10-DA015815, U10-DA015833, U10 DA015831, U10-DA020024, U10 DA013710,
U10 DA013038, U10 DA013035, R01 DA023230, P50 DA09241, U10-DA020036, K23
DA021512, N01DA-7-1134, P50 DA009241, U10 DA 13732, U10 DA013034, U10
DA013043, U10 DA013046, U10 DA013727, U10 DA015815, U10 DA015833, U10
DA020024, U10 DA020036, U10-DA013036, U10-DA013045, U10-DA013714,
U10-DA013720, U10-DA013732]; PHS HHS [904214, RMH0884772A]
NR 57
TC 30
Z9 30
U1 3
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0740-5472
J9 J SUBST ABUSE TREAT
JI J. Subst. Abus. Treat.
PD JUN
PY 2010
VL 38
IS 4
SU 1
BP S31
EP S43
DI 10.1016/j.jsat.2009.12.013
PG 13
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA 595AG
UT WOS:000277582500004
PM 20307793
ER
PT J
AU Nunes, EV
Ball, S
Booth, R
Brigham, G
Calsyn, DA
Carroll, K
Feaster, DJ
Hien, D
Hubbard, RL
Ling, W
Petry, NM
Rotrosen, J
Selzer, J
Stitzer, M
Tross, S
Wakim, P
Winhusen, T
Woody, G
AF Nunes, Edward V.
Ball, Samuel
Booth, Robert
Brigham, Gregory
Calsyn, Donald A.
Carroll, Kathleen
Feaster, Daniel J.
Hien, Denise
Hubbard, Robert L.
Ling, Walter
Petry, Nancy M.
Rotrosen, John
Selzer, Jeffrey
Stitzer, Maxine
Tross, Susan
Wakim, Paul
Winhusen, Theresa
Woody, George
TI Multisite effectiveness trials of treatments for substance abuse and
co-occurring problems: Have we chosen the best designs?
SO JOURNAL OF SUBSTANCE ABUSE TREATMENT
LA English
DT Article
DE Effectiveness; Design; Drug; HIV; Clinical trial
ID MOTIVATIONAL ENHANCEMENT THERAPY; METHADONE-MAINTENANCE TREATMENT; RISK
REDUCTION GROUPS; CONTINGENCY MANAGEMENT; RANDOMIZED-TRIAL; TREATMENT
PROGRAMS; BUPRENORPHINE-NALOXONE; COST-EFFECTIVENESS; USE OUTCOMES;
DRUG-USE
AB Multisite effectiveness trials such as those carried out in the National Drug Abuse Treatment Clinical Trials Network (CTN) are a critical step in the development and dissemination of evidence-based treatments because they address how such treatments perform in real-world clinical settings. As Brigham et al. summarized in a recent article (G. S. Brigham, D. J. Feaster, P. G. Wakim, & C. L. Dempsey C. L., 2009), several possible experimental designs may be chosen for such effectiveness trials. These include (a) a new treatment intervention (Tx) is compared to an existing mode of community based treatment as usual (TAU): Tx versus TAU; (b) a new intervention is added to TAU and compared to TAU alone: Tx + TAU versus TAU; or (c) a new intervention is added to TAU and compared to a control condition added to TAU: Tx + TAU versus control + TAU. Each of these designs addresses a different question and has different potential strengths and weaknesses. As of December 2009, the primary outcome paper had been published for 16 of the multisite randomized clinical trials conducted in the CTN, testing various treatments for drug abuse, HIV risk behavior, or related problems. This paper systematically examines, for each of the completed trials, the experimental design type chosen and its original rationale, the main findings of the trial, and the strengths and weaknesses of the design in hindsight. Based on this review, recommendations are generated to inform the design of future effectiveness trials on treatments for substance abuse, HIV risk, and other behavioral health problems. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Nunes, Edward V.; Hien, Denise; Selzer, Jeffrey; Tross, Susan] Columbia Univ, Dept Psychiat, New York State Psychiat Inst, Natl Drug Abuse Clin Trials Network, New York, NY 10032 USA.
[Ball, Samuel; Carroll, Kathleen] Yale Univ, Sch Med, APT Fdn, Natl Drug Abuse Clin Trials Network, West Haven, CT 06516 USA.
[Booth, Robert] Univ Colorado, Hlth Sci Ctr, Denver, CO USA.
[Brigham, Gregory] Maryhaven Inc, Res Inst, Natl Drug Abuse Clin Trials Network, Ohio Valley Node, Columbus, OH USA.
[Calsyn, Donald A.] Univ Washington, Dept Psychiat & Behav Sci, Natl Drug Abuse Clin Trials Network, Inst Alcohol & Drug Abuse, Seattle, WA 98195 USA.
[Feaster, Daniel J.] Univ Miami, Miller Sch Med, Ctr Studies Family, Dept Epidemiol & Publ Hlth,Natl Drug Abuse Clin T, Miami, FL 33136 USA.
[Hien, Denise] CUNY, Natl Drug Abuse Clin Trials Network, New York, NY 10021 USA.
[Hubbard, Robert L.] Duke Univ, Med Ctr, Inst Community Based Res, Natl Dev & Res Inst, Durham, NC USA.
[Ling, Walter] Univ Calif Los Angeles, David Geffen Sch Med, Natl Drug Abuse Clin Trials Network, Los Angeles, CA 90095 USA.
[Petry, Nancy M.] Univ Connecticut, Ctr Hlth, Dept Med, Natl Drug Abuse Clin Trials Network,Calhoun Cardi, Farmington, CT USA.
[Rotrosen, John] NYU, Sch Med, Vet Affairs New York Harbor Healthcare Syst, Natl Drug Abuse Clin Trials Network, New York, NY USA.
[Selzer, Jeffrey] Comm Phys Hlth, Albany, NY USA.
[Stitzer, Maxine] Johns Hopkins Univ, Sch Med, Bayview Med Ctr, Natl Drug Abuse Clin Trials Network, Baltimore, MD USA.
[Wakim, Paul] Natl Inst Drug Abuse, Ctr Clin Trials Network, NIH, Bethesda, MD USA.
[Winhusen, Theresa] Univ Cincinnati CinARC, Natl Drug Abuse Clin Trials Network, Cincinnati, OH USA.
[Woody, George] Univ Penn, Sch Med, Natl Drug Abuse Clin Trials Network, Philadelphia, PA 19104 USA.
RP Nunes, EV (reprint author), Columbia Univ, Dept Psychiat, New York State Psychiat Inst, Natl Drug Abuse Clin Trials Network, 1051 Riverside Dr,Unit 51, New York, NY 10032 USA.
EM nunesed@pi.cpmc.columbia.edu
RI Carroll, Kathleen/A-7526-2009; Feaster, Daniel/I-6079-2013;
OI Winhusen, Theresa/0000-0002-3364-0739; Brigham,
Gregory/0000-0003-1150-4493; Carroll, Kathleen/0000-0003-3263-3374;
Feaster, Daniel/0000-0002-6172-7460
FU NIDA NIH HHS [K24 DA022412-03, 5U10 DA013714, DA13045, K05 DA017009, K05
DA017009-07, K05 DA17009, K24 DA022412, U10 DA 13038, U10 DA013034, U10
DA013034-08, U10 DA013035, U10 DA013035-08, U10 DA013038, U10
DA013038-06, U10 DA013043, U10 DA013043-06, U10 DA013045, U10
DA013045-10, U10 DA013046, U10 DA013046-06, U10 DA013711, U10
DA013711-05, U10 DA013714, U10 DA013714-05, U10 DA013720, U10
DA013720-10, U10 DA013732, U10 DA013732-07, U10 DA13034, U10 DA13035,
U10 DA13038, U10 DA13043, U10 DA13045, U10 DA13046, U10 DA13711, U10
DA13720, U10 DA13732]
NR 41
TC 15
Z9 15
U1 2
U2 7
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0740-5472
J9 J SUBST ABUSE TREAT
JI J. Subst. Abus. Treat.
PD JUN
PY 2010
VL 38
IS 4
SU 1
BP S97
EP S112
DI 10.1016/j.jsat.2010.01.012
PG 16
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA 595AG
UT WOS:000277582500011
PM 20307801
ER
PT J
AU Tai, B
Straus, MM
Liu, D
Sparenborg, S
Jackson, R
McCarty, D
AF Tai, Betty
Straus, Michele M.
Liu, David
Sparenborg, Steven
Jackson, Ron
McCarty, Dennis
TI The first decade of the National Drug Abuse Treatment Clinical Trials
Network: Bridging the gap between research and practice to improve drug
abuse treatment
SO JOURNAL OF SUBSTANCE ABUSE TREATMENT
LA English
DT Article
DE Clinical Trials Network; Drug abuse treatment; Research
ID MOTIVATIONAL ENHANCEMENT THERAPY; METHADONE-MAINTENANCE TREATMENT;
PSYCHOSOCIAL TREATMENT PROGRAMS; MULTISITE RANDOMIZED-TRIAL;
VOUCHER-BASED INCENTIVES; PRIZE-BASED INCENTIVES; RISK REDUCTION GROUPS;
SUBSTANCE-ABUSE; CONTINGENCY MANAGEMENT; BUPRENORPHINE-NALOXONE
AB The National Institute on Drug Abuse established the National Drug Abuse Treatment Clinical Trials Network (CTN) in 1999 to improve the quality of addiction treatment using science as the vehicle. The network brings providers from community-based drug abuse treatment programs and scientists from university-based research centers together in an alliance that fosters bidirectional communication and collaboration. Collaboration enhanced the relevance of research to practice and facilitated the development and implementation of evidence-based treatments in community practice settings. The CTN's 20 completed trials tested pharmacological, behavioral, and integrated treatment interventions for adolescents and adults; more than 11,000 individuals participated in the trials. This article reviews the rationale for the CTN, describes the translation of its guiding principles into research endeavors, and anticipates the future evolution of clinical research within the Network. Published by Elsevier Inc.
C1 [Tai, Betty; Straus, Michele M.; Liu, David; Sparenborg, Steven] Natl Inst Drug Abuse, Ctr Clin Trials Network, NIH, Rockville, MD 20892 USA.
[Jackson, Ron] Evergreen Treatment Serv, Seattle, WA 98134 USA.
[McCarty, Dennis] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA.
RP Tai, B (reprint author), Natl Inst Drug Abuse, Ctr Clin Trials Network, NIH, Rockville, MD 20892 USA.
EM btai@nida.nih.gov
FU Intramural NIH HHS [Z99 DA999999]; NIDA NIH HHS [U10 DA013714, U10
DA013036, U10 DA013714-09, U10 DA013036-09, U10 DA 13036, U10 DA 13714]
NR 65
TC 38
Z9 38
U1 2
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0740-5472
J9 J SUBST ABUSE TREAT
JI J. Subst. Abus. Treat.
PD JUN
PY 2010
VL 38
IS 4
SU 1
BP S4
EP S13
DI 10.1016/j.jsat.2010.01.011
PG 10
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA 595AG
UT WOS:000277582500002
PM 20307794
ER
PT J
AU Wu, LT
Pan, JJ
Blazer, DG
Tai, B
Stitzer, ML
Woody, GE
AF Wu, Li-Tzy
Pan, Jeng-Jong
Blazer, Dan G.
Tai, Betty
Stitzer, Maxine L.
Woody, George E.
TI Using a latent variable approach to inform gender and racial/ethnic
differences in cocaine dependence: A National Drug Abuse Treatment
Clinical Trials Network study
SO JOURNAL OF SUBSTANCE ABUSE TREATMENT
LA English
DT Article
DE CTN Data Share; Clinical Trials Network; Cocaine dependence;
Differential item functioning; Multiple indicators-multiple causes model
ID SUBSTANCE USE DIAGNOSES; DSM-IV; EPIDEMIOLOGIC SURVEY; ALCOHOL
DEPENDENCE; USE DISORDERS; MARIJUANA USE; RISK; HETEROGENEITY;
COOCCURRENCE; PROGRESSION
AB This study applies a latent variable approach to examine gender and racial/ethnic differences in cocaine dependence, to determine the presence of differential item functioning (DIF) or item-response bias to diagnostic questions of cocaine dependence, and to explore the effects of DIF on the predictor analysis of cocaine dependence. The analysis sample included 682 cocaine users enrolled in two national multisite studies of the National Drug Abuse Treatment Clinical Trials Network (CTN). Participants were recruited from 14 community-based substance abuse treatment programs associated with the CTN, including 6 methadone and 8 outpatient nonmethadone programs. Factor and multiple indicators multiple causes (MIMIC) procedures evaluated the latent continuum of cocaine dependence and its correlates. MIMIC analysis showed that men exhibited lower odds of cocaine dependence than women (regression coefficient, beta = 0.34), controlling for the effects of DIF, years of cocaine use, addiction treatment history, comorbid drug dependence diagnoses, and treatment setting. There were no racial/ethnic differences in cocaine dependence; however, DIE by race/ethnicity was noted. Within the context of multiple community-based addiction treatment settings, women were more likely than men to exhibit cocaine dependence. Addiction treatment research needs to further evaluate gender-related differences in drug dependence in treatment entry and to investigate how these differences may affect study participation, retention, and treatment response to better serve this population. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Wu, Li-Tzy; Blazer, Dan G.] Duke Univ, Med Ctr, Duke Clin Res Inst, Dept Psychiat & Behav Sci,Sch Med, Durham, NC 27710 USA.
[Pan, Jeng-Jong] Vet Hlth Adm, Washington, DC 20024 USA.
[Tai, Betty] Natl Inst Drug Abuse, Bethesda, MD 20892 USA.
[Stitzer, Maxine L.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 20892 USA.
[Woody, George E.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19106 USA.
[Woody, George E.] Treatment Res Inst, Philadelphia, PA 19106 USA.
RP Wu, LT (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, Dept Psychiat & Behav Sci,Sch Med, Box 3419, Durham, NC 27710 USA.
EM litzy.wu@duke.edu
FU NIDA NIH HHS [U10 DA013034-10, 5U10DA013034, HHSN271200522071C, K05
DA017009, K05 DA017009-07, K05DA017009, R01 DA019623, R01 DA019623-03,
R01 DA019901, R01 DA019901-03, R01DA019623, R01DA019901, R21 DA 027503,
R21 DA027503, R21 DA027503-01, R21DA027503, R33 DA027503, U10 DA013034,
U10 DA013043, U10 DA013043-10, U10DA013043]; PHS HHS [HHSN271200522071C]
NR 44
TC 10
Z9 10
U1 5
U2 11
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0740-5472
J9 J SUBST ABUSE TREAT
JI J. Subst. Abus. Treat.
PD JUN
PY 2010
VL 38
IS 4
SU 1
BP S70
EP S79
DI 10.1016/j.jsat.2009.12.011
PG 10
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA 595AG
UT WOS:000277582500008
PM 20307798
ER
PT J
AU Kebebew, E
AF Kebebew, Electron
TI Nile Red Staining Helps Select Cells with Adrenocortical Progenitor
Cell-Like Phenotype
SO JOURNAL OF SURGICAL RESEARCH
LA English
DT Editorial Material
ID RAT ADRENAL-CORTEX
C1 NCI, Endocrine Surg Sect, Surg Branch, CRC, Bethesda, MD 20892 USA.
RP Kebebew, E (reprint author), NCI, Endocrine Surg Sect, Surg Branch, CRC, Room 4-5952,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA.
EM kebebewe@mail.nih.gov
NR 4
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 0022-4804
J9 J SURG RES
JI J. Surg. Res.
PD JUN 1
PY 2010
VL 161
IS 1
BP 34
EP 35
DI 10.1016/j.jss.2009.07.019
PG 2
WC Surgery
SC Surgery
GA 594KS
UT WOS:000277537200007
PM 20031173
ER
PT J
AU Findling, RL
Johnson, JL
McClellan, J
Frazier, JA
Vitiello, B
Hamer, RM
Lieberman, JA
Ritz, L
McNamara, NK
Lingler, J
Hlastala, S
Pierson, L
Puglia, M
Maloney, AE
Kaufman, EM
Noyes, N
Sikich, L
AF Findling, Robert L.
Johnson, Jacqueline L.
McClellan, Jon
Frazier, Jean A.
Vitiello, Benedetto
Hamer, Robert M.
Lieberman, Jeffrey A.
Ritz, Louise
McNamara, Nora K.
Lingler, Jacqui
Hlastala, Stefanie
Pierson, Leslie
Puglia, Madeline
Maloney, Ann E.
Kaufman, Emily Michael
Noyes, Nancy
Sikich, Linmarie
TI Double-Blind Maintenance Safety and Effectiveness Findings From the
Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) Study
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Article
DE adolescent; schizophrenia; schizoaffective disorder; antipsychotic;
treatment
ID ANTIPSYCHOTIC-DRUGS; 2ND-GENERATION ANTIPSYCHOTICS; DISORDERS TEOSS;
TRIAL
AB Objective: To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders. Method: Patients (8 to 19 years old) who had improved during an 8-week, randomized, double-blind acute trial of olanzapine, risperidone, or molindone (plus benztropine) were eligible to continue on the same medication for up to 44 additional weeks under double-blind conditions. Adjunctive medications were allowed according to defined algorithms Standardized symptom, safety, and functional assessments were conducted every 4 weeks. Results: Of the 116 youths randomized in the acute trial, 54 entered maintenance treatment (molindone, n = 20; olanzapine, n = 13; risperidone, n = 21). Fourteen (26%) completed 44 weeks of treatment. Adverse effects (n = 15), inadequate efficacy (n = 14), or study nonadherence (n = 8) were the most common reasons for discontinuation. The three treatment arms did not significantly differ in symptom decrease or time to discontinuation. Akathisia was more common with molindone and elevated prolactin concentrations more common with risperidone. Although weight gain and metabolic adverse events had occurred more often with olanzapine and risperidone during the acute trial, no significant between-drug differences emerged in most of these parameters during maintenance treatment. Conclusions: Only 12% of youths with early-onset schizophrenia spectrum disorders continued on their originally randomized treatment at 52 weeks. No agent demonstrated superior efficacy, and all were associated with side effects, including weight gain. Improved treatments are needed for early-onset schizophrenia spectrum disorders. Clinical trial registry information Treatment of Schizophrenia and Related Disorders in Children and Adolescents; URL: http://www.clinicaltrials.gov, unique identifier: NCT00053703. J. Am. Acad. Child Adolesc. Psychiatry, 2010;49(6):583-594.
C1 [Findling, Robert L.; McNamara, Nora K.; Lingler, Jacqui] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[McClellan, Jon; Hlastala, Stefanie] Univ Washington, Seattle, WA 98195 USA.
[Pierson, Leslie] Seattle Childrens Hosp, Div Child Psychiat, Seattle, WA USA.
[Vitiello, Benedetto] NIMH, Bethesda, MD 20892 USA.
[Lieberman, Jeffrey A.] Columbia Univ, New York, NY 10027 USA.
[Johnson, Jacqueline L.; Hamer, Robert M.; Lieberman, Jeffrey A.; Puglia, Madeline; Maloney, Ann E.; Sikich, Linmarie] Univ N Carolina, Chapel Hill, NC USA.
[Frazier, Jean A.; Kaufman, Emily Michael; Noyes, Nancy] Harvard Univ, Sch Med, Cambridge Hlth Alliance, Cambridge, MA 02138 USA.
RP Findling, RL (reprint author), 10524 Euclid Ave,Suite 1155A, Cleveland, OH 44106 USA.
EM robert.findling@uhhospitals.org
FU National Institute of Mental Health [MH-61355]; Case Western Reserve
University [MH-61464]; University of Washington [MH-62726]; Harvard
Medical School [MH-61528]; University of North Carolina [K23 MH-018021,
K23 MH-70570]; National Institutes of Health career development;
National Institutes of Health; Clinical Research Centers at Seattle
Children's Hospital, University of Washington [M01-RR000371]; University
of North Carolina at Chapel Hill [M01RR00046, U54RR024383]
FX This study was supported by National Institute of Mental Health grants
MH-61355 (Dr. Findling) to Case Western Reserve University, MH-61464
(Dr. McClellan) to the University of Washington, MH-62726 (Dr. Frazier)
to Harvard Medical School, and MH-61 528 (Dr. Sikich) to the University
of North Carolina. Drs. Sikich (K23 MH-018021 and Hlastala (K23
MH-70570) were also supported by National Institutes of Health career
development awards. The research was conducted in National Institutes of
Health-supported Clinical Research Centers at Seattle Children's
Hospital, University of Washington (M01-RR000371, and the University of
North Carolina at Chapel Hill (M01RR00046 and U54RR024383).
NR 17
TC 49
Z9 50
U1 1
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0890-8567
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD JUN
PY 2010
VL 49
IS 6
BP 583
EP 594
DI 10.1016/j.jaac.2010.03.013
PG 12
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 602TA
UT WOS:000278160500006
PM 20494268
ER
PT J
AU Kelly, JJ
Freeman, AF
Wang, H
Cowen, EW
Kong, HH
AF Kelly, Jeffrey J.
Freeman, Alexandra F.
Wang, Heng
Cowen, Edward W.
Kong, Heidi H.
TI An Amish boy with recurrent ulcerations of the lower extremities,
telangiectases of the hands, and chronic lung disease
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Editorial Material
DE chronic lung disease; immunodeficiency; leg ulcers; prolidase
deficiency; skin; telangiectasia; ulcers
ID HYPER-IGE SYNDROME; PROLIDASE DEFICIENCY; MUTATION; IMINOPEPTIDURIA;
THERAPY; ULCERS; PEPD
C1 [Cowen, Edward W.; Kong, Heidi H.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Kelly, Jeffrey J.] Walter Reed Army Med Ctr, Dept Dermatol, Washington, DC 20307 USA.
[Freeman, Alexandra F.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Wang, Heng] DDC Clin Special Needs Children, Middlefield, OH USA.
RP Kong, HH (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 10,Room 12N238,10 Ctr Dr,MSC 1908, Bethesda, MD 20892 USA.
EM konghe@mail.nih.gov
OI Kong, Heidi/0000-0003-4424-064X
FU Intramural NIH HHS [Z99 CA999999]
NR 19
TC 7
Z9 7
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0190-9622
J9 J AM ACAD DERMATOL
JI J. Am. Acad. Dermatol.
PD JUN
PY 2010
VL 62
IS 6
BP 1031
EP 1034
DI 10.1016/j.jaad.2009.12.038
PG 4
WC Dermatology
SC Dermatology
GA 599UW
UT WOS:000277940300016
PM 20466176
ER
PT J
AU Thanassoulis, G
Massaro, JM
Cury, R
Manders, E
Benjamin, EJ
Vasan, RS
Cupple, LA
Hoffmann, U
O'Donnell, CJ
Kathiresan, S
AF Thanassoulis, George
Massaro, Joseph M.
Cury, Ricardo
Manders, Emily
Benjamin, Emelia J.
Vasan, Ramachandran S.
Cupple, L. Adrienne
Hoffmann, Udo
O'Donnell, Christopher J.
Kathiresan, Sekar
TI Associations of Long-Term and Early Adult Atherosclerosis Risk Factors
With Aortic and Mitral Valve Calcium
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE aortic valve; atherosclerosis; calcification; mitral valve; stenosis
ID LOW-DENSITY-LIPOPROTEIN; CORONARY-HEART-DISEASE; METABOLIC SYNDROME;
DIABETES-MELLITUS; CLINICAL FACTORS; ANULAR CALCIUM; EARLY LESION;
STENOSIS; PROGRESSION; CALCIFICATION
AB Objectives To determine the association of long-term exposure to atherosclerosis risk factors with valvular calcification.
Background Traditional atherosclerosis risk factors have been associated with aortic and mitral valve calcium in cross-sectional studies, but long-term prospective data are lacking.
Methods This was a prospective, community-based cohort study with 27-year follow-up (median follow-up 26.9 years; range 23.1 to 29.6 years). Participants from the Framingham Offspring Study (n = 1,323, enrolled between 1971 and 1975, mean age at enrollment 34 +/- 9 years; 52% women) underwent cardiac multidetector computed tomography assessment between 2002 and 2005. Associations between the long-term average of each cardiovascular risk factor and valve calcium were estimated using logistic regression.
Results Aortic valve calcium was present in 39% of participants and mitral valve calcium in 20%. In multivariable models, the odds ratio for aortic valve calcium associated with every SD increment in long-term mean total cholesterol was 1.74 (p < 0.0001); with every SD increment in high-density lipoprotein cholesterol, it was 0.77 (p = 0.002); and with every 9 cigarettes smoked per day, it was 1.23 (p = 0.002). Associations of similar magnitude were seen for mitral valve calcium. The mean of 3 serum C-reactive protein measurements was associated with mitral valve calcium (odds ratio: 1.29 per SD increment in C-reactive protein levels; p = 0.002). A higher Framingham risk score in early adulthood (40 years age or younger) was associated with increased prevalence and severity of aortic valve calcium measured 3 decades later.
Conclusions Exposure to multiple atherosclerotic risk factors starting in early to mid-adulthood is associated with aortic and mitral valve calcium. Studies evaluating early risk factor modification to reduce the burden of valve disease are warranted. (J Am Coll Cardiol 2010; 55: 2491-8) (C) 2010 by the American College of Cardiology Foundation
C1 [Kathiresan, Sekar] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Cury, Ricardo; Hoffmann, Udo] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Radiol, Boston, MA 02114 USA.
[Cury, Ricardo; Hoffmann, Udo] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA.
[Thanassoulis, George; O'Donnell, Christopher J.; Kathiresan, Sekar] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Kathiresan, Sekar] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Thanassoulis, George; Manders, Emily; Benjamin, Emelia J.; Vasan, Ramachandran S.; Cupple, L. Adrienne; O'Donnell, Christopher J.; Kathiresan, Sekar] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Kathiresan, Sekar] Harvard Univ, Cambridge, MA 02138 USA.
[Kathiresan, Sekar] MIT, Program Med & Populat Genet, Broad Inst, Cambridge, MA 02139 USA.
[Thanassoulis, George] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Massaro, Joseph M.; Cupple, L. Adrienne] Boston Univ, Dept Biostat, Boston, MA 02118 USA.
[Benjamin, Emelia J.; Cupple, L. Adrienne] Boston Univ, Dept Epidemiol, Boston, MA 02118 USA.
[Massaro, Joseph M.] Boston Univ, Dept Math & Stat, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Evans Dept Med, Boston, MA 02118 USA.
[Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
[O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA.
RP Kathiresan, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN 5-252, Boston, MA 02114 USA.
EM skathiresan@partners.org
OI Massaro, Joseph/0000-0002-2682-4812; Ramachandran,
Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336
FU National Heart, Lung, and Blood Institute [N01-HC-25195]; Canadian
Institute of Health Research; Fonds de Recherche en Sante du Quebec;
Astellas Pharma; Pfizer; GE Healthcare; American College of Cardiology
Foundation/Merck; GlaxoSmithKline Research & Education Foundation;
Alnylam Pharmaceuticals
FX From the *National Heart, Lung, and Blood Institute's Framingham Heart
Study, Framingham, Massachusetts; dagger Cardiology Division,
Cardiovascular Research Center, Center for Human Genetic Research, and
parallel to Radiology Division and Cardiac MR PET CT Program,
Massachusetts General Hospital, Harvard Medical School, Boston,
Massachusetts; Program in Medical and Population Genetics, Broad
Institute of Massachusetts Institute of Technology and Harvard
University, Cambridge, Massachusetts; #School of Medicine, Departments
of **Biostatistics dagger dagger Epidemiology, Mathematics and
Statistics, Evans Department of Medicine; parallel to parallel to
Whitaker Cardiovascular Institute, Boston University, Boston,
Massachusetts; and the Division of Intramural Research (COD), National
Heart, Lung, and Blood Institute, Bethesda, Maryland. This work was
supported by the National Heart, Lung, and Blood Institute's Framingham
Heart Study (contract no. N01-HC-25195). Dr. Thanassoulis is supported
by a Research Fellowship by the Canadian Institute of Health Research
and the Fonds de Recherche en Sante du Quebec. Dr. Cury has received
research grants from Astellas Pharma, Pfizer, and GE Healthcare, and is
a consultant for Astellas Pharma. Dr. Kathiresan's efforts were
supported by the American College of Cardiology Foundation/Merck Adult
Cardiology Research Fellowship Award and the GlaxoSmithKline Research &
Education Foundation for Cardiovascular Disease Young Investigator
Award. Dr. Kathiresan serves on a scientific advisory board for Merck,
Daiichi Sankyo, and Pfizer, and has received research funding from
Pfizer and Alnylam Pharmaceuticals. Drs. O'Donnell and Kathiresan
contributed equally to this work.
NR 43
TC 29
Z9 29
U1 0
U2 2
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 JUN 1
PY 2010
VL 55
IS 22
BP 2491
EP 2498
DI 10.1016/j.jacc.2010.03.019
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 600ZB
UT WOS:000278026600010
PM 20510217
ER
PT J
AU Kaileh, M
Sen, R
AF Kaileh, Mary
Sen, Ranjan
TI Role of NF-kappa B in the Anti-Inflammatory Effects of Tocotrienols
SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION
LA English
DT Review
DE NF-kappa B; tocotrienols; inflammation
ID GAMMA-TOCOTRIENOL; SIGNALING PATHWAY; ALPHA-TOCOTRIENOL; VITAMIN-E;
CELL-PROLIFERATION; GENE-EXPRESSION; PROTEIN; SUPPRESSION; ACTIVATION;
TOCOPHEROL
AB The NF-kappa B family of transcription factors regulates genes that are critical for inflammation and immunity. In most cells. NF-kappa B function is induced upon activation of cells by various stimuli. However, constitutive NF-kappa B activity is an equally important aspect of NF-kB function that is particularly relevant to chronic inflammation and cancer. Here, we provide a brief overview of NF-kappa B biology and discuss the role of NF-kappa B in mediating the anti-inflammatory effects of tocotrienols
The NF-kappa B family of transcription factors is a central player in the regulation of inflammation and immune responses. Consequently, NF-kappa B dysregulation has been implicated in diverse human pathologies ranging from autoimmune diseases to cancers. Additionally, there is considerable interest in the contribution of NF-kappa B-mediated chronic inflammation in aging. Because NF-kappa B dependent gene regulation is important in virtually all mammalian cell types, it is critical to keep in mind some basic features of its functions when considering
C1 [Kaileh, Mary; Sen, Ranjan] NIA, Lab Cellular & Mol Biol, Baltimore, MD 21224 USA.
RP Kaileh, M (reprint author), NIA, Lab Cellular & Mol Biol, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM senra@mail.nih.gov
FU National Institute on Aging (Baltimore, MD)
FX The authors are supported by the Intramural Research Program of the
National Institute on Aging (Baltimore, MD).
NR 34
TC 12
Z9 13
U1 0
U2 8
PU AMER COLLEGE NUTRITION
PI CLEARWATER
PA 300 SOUTH DUNCAN AVENUE, STE 225, CLEARWATER, FL 33755 USA
SN 0731-5724
J9 J AM COLL NUTR
JI J. Am. Coll. Nutr.
PD JUN
PY 2010
VL 29
IS 3
SU S
BP 334S
EP 339S
PG 6
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 653FC
UT WOS:000282072700010
PM 20823493
ER
PT J
AU Rahbari, R
Sansano, IG
Elaraj, DM
Duh, QY
Clark, OH
Kebebew, E
AF Rahbari, Reza
Sansano, Ileana G.
Elaraj, Dina M.
Duh, Quan-Yang
Clark, Orlo H.
Kebebew, Electron
TI Prior Head and Neck Radiation Exposure Is Not a Contraindication to
Minimally Invasive Parathyroidectomy
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Article
ID PRIMARY HYPERPARATHYROIDISM; IRRADIATION; DISEASE; THERAPY; TUMORS;
GLAND
AB BACKGROUND: Most patients with primary hyperparathyroidism can have a minimally invasive parathyroidectomy based on localization studies showing single-gland disease. In patients with a history of head and neck irradiation, due to the increased risk of multigland disease and risk of concurrent thyroid cancer, minimally invasive parathyroidectomy is considered by some to be a contraindication. We postulated that previous history of head and neck irradiation should not be a contraindication for minimally invasive parathyroidectomy and tested this hypothesis in a prospective cohort of patients undergoing parathyroidectomy for primary hyperparathyroidism.
STUDY DESIGN: We performed a retrospective analysis of a prospective database of 491 consecutive parathyroidectomies performed between May 2005 and May 2007 at a tertiary referral medical center.
RESULTS: Fifty-two (12.6%) patients had a history of head and neck irradiation and 360 (87.4%) had no exposure to radiation. The 2 groups had no significant difference in terms of gender or ethnicity. The radiation group was older, with an average age of 65.1 years versus 58.1 years (p < 0.0009). There was no significant difference in concurrent benign thyroid neoplasm, thyroid cancer, and type of parathyroid disease (single vs multigland) in the 2 groups. There was no significant difference in the operative approach used between the 2 groups (focused vs unilateral or bilateral).
CONCLUSIONS: Head and neck irradiation should not be a contraindication for minimally invasive parathyroidectomy in patients with primary hyperparathyroidism in the setting of preoperative localization studies showing single-gland disease and no concurrent thyroid neoplasm. Furthermore, history of head and neck irradiation is associated with a later age of presentation for parathyroidectomy. (J Am Coll Surg 2010;210:942-948. (C) 2010 by the American College of Surgeons)
C1 [Kebebew, Electron] NCI, Surg Branch, CRC, NIH, Bethesda, MD 20892 USA.
[Sansano, Ileana G.; Duh, Quan-Yang; Clark, Orlo H.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA.
[Elaraj, Dina M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
RP Kebebew, E (reprint author), NCI, Surg Branch, CRC, NIH, Room 4-5952,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA.
EM kebebewe@mail.nih.gov
NR 25
TC 1
Z9 2
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD JUN
PY 2010
VL 210
IS 6
BP 942
EP 948
DI 10.1016/j.jamcollsurg.2010.02.041
PG 7
WC Surgery
SC Surgery
GA 609IH
UT WOS:000278649100008
PM 20510803
ER
PT J
AU Moalem, J
Ruan, DT
Farkas, RL
Shen, WT
Kebebew, E
Duh, QY
Clark, OH
AF Moalem, Jacob
Ruan, Daniel T.
Farkas, Rachel L.
Shen, Wen T.
Kebebew, Electron
Duh, Quan Y.
Clark, Orlo H.
TI Patterns of Antibiotic Prophylaxis Use for Thyroidectomy and
Parathyroidectomy: Results of an International Survey of Endocrine
Surgeons
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Article
ID AMERICAN-HEART-ASSOCIATION; BACTERIAL-ENDOCARDITIS; NECK-SURGERY;
PREVENTION; INFECTION; RECOMMENDATIONS; COMPLICATIONS
AB BACKGROUND: Although cervical endocrine operations are classified as clean cases, and prophylactic antibiotics (pABX) are generally not indicated, practice patterns vary.
STUDY DESIGN: We distributed an Internet-based survey to all members of the American and International Associations for Endocrine Surgeons. As a second component of our study, University of California San Francisco hospital records were queried for all readmissions or reoperations within 30 days after thyroidectomy, parathyroidectomy, or neck dissections between January 1, 1999 and December 30, 2007.
RESULTS: Of the 275 endocrine surgeons who responded, 62% "almost never" used pABX and 26.2% administered pABX "almost always." Surgeons' annual caseload (p = 0.21), their experience with past patients who had minor (p = 0.33) or severe (p = 0.83) surgical site infections (SSI) or adverse reactions to antibiotics (p = 0.78) were not associated with their likelihood to prescribe pABX. In the previous 3 years, most surgeons reported treating patients with minor SSIs, and 30% of surgeons treated more than 1 severe SSI. Surgeons who worked in community hospitals were more likely to give pABX than were surgeons in affiliated or university hospitals (49.6% vs 31.8% and 24.5%, respectively (p = 0.04). Unlike European (8.8%) or American surgeons (27.9%), surgeons in Asia were most likely to give pABX "almost always" (58.3%, p = 0.0001). Two-thirds of surgeons would not want antibiotics if they, themselves, needed a cervical operation. Five of the 4,541 patients (0.11%) who underwent cervical operations were readmitted for infectious complications.
CONCLUSIONS: Infectious complications after endocrine cervical operations are rare and the use of preoperative antibiotics varies widely. Prescribing behavior appears dogmatic in that 90% of surgeons give preoperative antibiotics almost always or almost never. (J Am Coll Surg 2010;210:949-956. (C) 2010 by the American College of Surgeons)
C1 [Moalem, Jacob; Farkas, Rachel L.] Univ Rochester, Med Ctr, Dept Surg, Rochester, NY 14642 USA.
[Ruan, Daniel T.] Brigham & Womens Med Ctr, Boston, MA USA.
[Shen, Wen T.; Duh, Quan Y.; Clark, Orlo H.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Kebebew, Electron] NIH, Surg Branch, Washington, DC USA.
RP Moalem, J (reprint author), Univ Rochester, Med Ctr, Dept Surg, 601 Elmwood Ave,Box Surg, Rochester, NY 14642 USA.
NR 26
TC 7
Z9 8
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD JUN
PY 2010
VL 210
IS 6
BP 949
EP 956
DI 10.1016/j.jamcollsurg.2010.02.040
PG 8
WC Surgery
SC Surgery
GA 609IH
UT WOS:000278649100009
PM 20510804
ER
PT J
AU Hajjar, I
Kritchevsky, S
Newman, AB
Li, RL
Yaffe, K
Simonsick, EM
Lipsitz, LA
AF Hajjar, Ihab
Kritchevsky, Stephen
Newman, Anne B.
Li, Rongling
Yaffe, Kristine
Simonsick, Eleanor M.
Lipsitz, Lewis A.
CA Hlth Aging & Body Composit Study
TI Renin Angiotensin System Gene Polymorphisms Modify
Angiotensin-Converting Enzyme Inhibitors' Effect on Cognitive Function:
The Health, Aging and Body Composition Study
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE hypertension; cognitive function; angiotensin-converting enzyme
inhibitors; angiotensinogen gene
ID BLOOD-PRESSURE; M235T POLYMORPHISM; EXECUTIVE CONTROL; DISEASE;
HYPERTENSION; RAT; ASSOCIATION; IMPAIRMENT; DEMENTIA; PROMOTER
AB OBJECTIVES: To investigate the effect of polymorphisms in renin angiotensin system genes on the association between angiotensin-converting enzyme inhibitor (ACEI) exposure and global and executive cognitive function in the Health, Aging and Body Composition study.
DESIGN: Cohort study.
SETTING: Community.
PARTICIPANTS: Three thousand seventy-five participants: mean age 73.6, 58% Caucasian, 52% female, 15% taking ACE-Is, 8 years of follow-up.
MEASUREMENTS: The outcomes were longitudinal change in Executive Clock Drawing Test-1 (CLOX1), the Digit Symbol Substitution test, and the Modified Mini-Mental State Examination. The genetic polymorphisms included angiotensin-converting enzyme insertion deletion (ACEID) in the ACE gene and the M235T and 6AG polymorphisms in the angiotensinogen (AGT) gene.
RESULTS: For the CLOX1 outcome, there was significant interaction between 6AG and M235T polymorphisms in the AGT gene and angiotensin-converting enzyme inhibitors (ACE-Is) in Caucasian participants (P = .01 for both polymorphisms) independent of blood pressure levels. Specifically, ACE-I exposure was protective against CLOX1 score decline in carriers of the AA genotype of the 6AG and the CC genotype of the M235T (for the ACE-I vs non-ACEI groups, P = .01 for 6AG and P = .005 for M235T) but not the other genotypes. These associations were not significant with other cognitive tests, with ACEID, or in African Americans.
CONCLUSION: ACE-Is may provide a protective effect on executive function in Caucasians with AGT gene polymorphisms known to be associated with greater renin angiotensin system activity. If confirmed in a pharmacogenetic trial, ACE-Is may be found to have additional cognitive protection in a select group of elderly individuals. J Am Geriatr Soc 58: 1035-1042, 2010.
C1 [Hajjar, Ihab] Harvard Univ, Sch Med, Inst Aging Res Hebrew SeniorLife, Beth Israel Deaconess Med Ctr, Boston, MA 02131 USA.
[Hajjar, Ihab; Lipsitz, Lewis A.] Beth Israel Deaconess Med Ctr, Dept Med, Div Gerontol, Boston, MA 02215 USA.
[Kritchevsky, Stephen] Wake Forest Univ, Sch Med, Dept Internal Med Gerontol & Geriatr, Winston Salem, NC 27109 USA.
[Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol & Med, Pittsburgh, PA USA.
[Li, Rongling] NHGRI, Off Populat Genom, NIH, Bethesda, MD 20892 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat Neurol & Epidemiol, San Francisco, CA 94143 USA.
[Simonsick, Eleanor M.] NIA, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Hajjar, I (reprint author), Harvard Univ, Sch Med, Inst Aging Res Hebrew SeniorLife, Beth Israel Deaconess Med Ctr, 1200 Ctr St, Boston, MA 02131 USA.
EM Ihabhajjar@hrca.harvard.edu
RI Newman, Anne/C-6408-2013;
OI Newman, Anne/0000-0002-0106-1150; Kritchevsky,
Stephen/0000-0003-3336-6781
FU NIA [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, K23AG30057]; NIH,
National Institute on Aging; [AG031155]
FX Health ABC was funded by the NIA contracts N01-AG-6-2101, N01-AG-6-2103,
and N01-AG-6-2106. This analysis was supported by an NIA grant
(K23AG30057) to Dr. Hajjar. Dr. Yaffe is supported in part by AG031155.
Dr. Lipsitz holds the Irving and Edyth S. Usen and Family Chair in
Geriatric Medicine at Hebrew SeniorLife. This research was also
supported in part by the Intramural Research Program of the NIH,
National Institute on Aging.
NR 31
TC 9
Z9 10
U1 1
U2 4
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 JUN
PY 2010
VL 58
IS 6
BP 1035
EP 1042
DI 10.1111/j.1532-5415.2010.02860.x
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 604WO
UT WOS:000278309400003
PM 20722844
ER
PT J
AU Louie, GH
Ward, MM
AF Louie, Grant H.
Ward, Michael M.
TI Sex Disparities in Self-Reported Physical Functioning: True Differences,
Reporting Bias, or Incomplete Adjustment for Confounding?
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE self-report; physical functioning; gender disparity; NHANES III
ID GENDER-DIFFERENCES; OLDER PERSONS; US POPULATION; HEALTH-STATUS; MUSCLE
MASS; DISABILITY; ADULTS; LIMITATIONS; IMPAIRMENT; PREDICTORS
AB OBJECTIVES: To determine whether sex disparities in self-reported physical functioning remain after adjusting for potential confounding factors and to assess associations for possible reporting bias.
DESIGN: Cross-sectional survey.
SETTING: U. S. population of noninstitutionalized older adults.
PARTICIPANTS: Women and men aged 60 and older (N = 5,396) who participated in the Third National Health and Nutrition Examination Survey.
MEASUREMENTS: Degree of self-reported limitation in 11 physical functions.
RESULTS: In unadjusted models, women reported more limitations than men in 10 of 11 tasks. In multivariate ordinal logistic regression models that included adjustment for age, race or ethnicity, education level, comorbidities, smoking, hemoglobin, serum albumin, knee pain, body mass index, skeletal muscle index, and physical performance tests, women reported more limitations only in lifting or carrying 10 pounds (adjusted odds ratio = 2.03, 95% confidence interval = 1.45-2.84). There was no evidence of systematic reporting differences between men and women for limitations in lifting or carrying 10 pounds relative to the degree of limitation predicted by the model.
CONCLUSION: Older women have similar degrees of self-reported limitation in physical functioning as older men of the same age, health, and physical abilities. J Am Geriatr Soc 58: 1117-1122, 2010.
C1 [Louie, Grant H.; Ward, Michael M.] NIAMSD, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Ward, MM (reprint author), NIAMS, NIH, IRP, CRC, Bldg 10,Room 4-1339,10 Ctr Dr,MSC 1468, Bethesda, MD 20892 USA.
EM wardm1@mail.nih.gov
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases at
the National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute of Arthritis and Musculoskeletal and Skin Diseases at
the National Institutes of Health.
NR 29
TC 14
Z9 14
U1 1
U2 4
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 JUN
PY 2010
VL 58
IS 6
BP 1117
EP 1122
DI 10.1111/j.1532-5415.2010.02858.x
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 604WO
UT WOS:000278309400014
PM 20487076
ER
PT J
AU O'Leary, TJ
Slutsky, JR
Bernard, MA
AF O'Leary, Timothy J.
Slutsky, Jean R.
Bernard, Marie A.
TI Comparative Effectiveness Research Priorities at Federal Agencies: The
View from the Department of Veterans Affairs, National Institute on
Aging, and Agency for Healthcare Research and Quality
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE patient outcomes; comparative effectiveness; research
ID LIPID-LOWERING TREATMENT; ATTACK TRIAL ALLHAT; MAJOR OUTCOMES
AB In the last year, attention has been focused on translating federally sponsored health research into better health for Americans. Since the passage of the American Recovery and Reinvestment Act (ARRA) on February 17, 2009, ARRA funds to support Comparative Effectiveness Research (CER) have increased this focus. A large proportion of topical areas of interest in CER affects the older segment of the population. The Department of Veterans Affairs (VA), the National Institute on Aging (NIA), and the Agency for Healthcare Research and Quality (AHRQ) have supported robust research portfolios focused on aging populations that meet the varying definitions of CER. This short article briefly describes the research missions of the AHRQ, NIA, and VA. The various definitions of CER as the Congressional Budget Office, the Institute of Medicine, and the ARRA-established Federal Coordinating Council have put forward, as well as important topics for which CER is particularly needed, are then reviewed. Finally, approaches in which the three agencies support CER involving the aging population are set forth and opportunities for future CER research outlined. J Am Geriatr Soc 58: 1187-1192, 2010.
C1 [Bernard, Marie A.] NIA, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
[O'Leary, Timothy J.] US EPA, Off Res & Dev, Dept Vet Affairs, Washington, DC 20460 USA.
[Slutsky, Jean R.] Agcy Healthcare Res & Qual, Ctr Outcomes & Evidence, Rockville, MD USA.
RP Bernard, MA (reprint author), NIA, Dept Hlth & Human Serv, NIH, Bldg 31,5C-35,31 Ctr Dr,MSC 2292, Bethesda, MD 20892 USA.
EM mbernard@nia.nih.gov
FU Intramural NIH HHS [Z99 AG999999]
NR 13
TC 7
Z9 7
U1 0
U2 0
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 JUN
PY 2010
VL 58
IS 6
BP 1187
EP 1192
DI 10.1111/j.1532-5415.2010.02939.x
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 604WO
UT WOS:000278309400025
PM 20936736
ER
PT J
AU Chen, LM
Kim, SM
Eisner, C
Oppermann, M
Huang, YN
Mizel, D
Li, LL
Chen, M
Lopez, MLS
Weinstein, LS
Gomez, RA
Schnermann, J
Briggs, JP
AF Chen, Limeng
Kim, Soo Mi
Eisner, Christoph
Oppermann, Mona
Huang, Yuning
Mizel, Diane
Li, Lingli
Chen, Min
Lopez, Maria Luisa Sequeira
Weinstein, Lee S.
Gomez, Roberto A.
Schnermann, Jurgen
Briggs, Josephine P.
TI Stimulation of Renin Secretion by Angiotensin II Blockade is Gs
alpha-Dependent
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID GENE-KNOCKOUT MICE; CORTICAL CYCLOOXYGENASE-2 EXPRESSION; NITRIC-OXIDE
SYNTHASE; JUXTAGLOMERULAR CELLS; MACULA DENSA; RECEPTOR GENE;
CROSS-TALK; IN-VITRO; INHIBITION; RELEASE
AB Angiotensin II converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB) presumably stimulate renin secretion by interrupting angiotensin II feedback inhibition. The increase in cytosolic calcium caused by activation of Gq-coupled AT1 receptors may mediate the renin-inhibitory effect of angiotensin II at the cellular level, implying that ACEI and ARB may work by reducing intracellular calcium. Here, we investigated whether angiotensin II blockade acts predominantly through Gs-mediated stimulation of adenylyl cyclase (AC) by testing the effect of ACEI and ARB in mice with juxtaglomerular cell-specific deficiency of the AC-stimulatory Gs alpha. The ACEI captopril and quinaprilate and the ARB candesartan significantly increased plasma renin concentration (PRC) to 20 to 40 times basal PRC in wild-type mice but did not significantly alter PRC in Gs alpha-deficient mice. Captopril also completely abrogated renin stimulation in wild-type mice after co-administration of propranolol, indomethacin, and L-NAME. Treatment with enalapril and a low-NaCl diet for 7 days led to a 35-fold increase in PRC among wild-type mice but no significant change in PRC among Gsa-deficient mice. Three different pharmacologic inhibitors of AC reduced the stimulatory effect of captopril by 70% to 80%. In conclusion, blockade of angiotensin II stimulates renin synthesis and release indirectly through the action of ligands that activate the cAMP/PKA pathway in a Gs alpha-dependent fashion, including catecholamines, prostaglandins, and nitric oxide.
C1 [Chen, Limeng; Kim, Soo Mi; Eisner, Christoph; Oppermann, Mona; Huang, Yuning; Mizel, Diane; Li, Lingli; Chen, Min; Weinstein, Lee S.; Schnermann, Jurgen; Briggs, Josephine P.] NIDDKD, NIH, Bethesda, MD 20892 USA.
[Chen, Limeng] Beijing Union Med Coll Hosp, Beijing, Peoples R China.
[Lopez, Maria Luisa Sequeira; Gomez, Roberto A.] Univ Virginia, Dept Pediat, Charlottesville, VA USA.
RP Briggs, JP (reprint author), NIDDKD, NIH, 9000 Rockville Pike,Bldg 31,Room 2B11, Bethesda, MD 20892 USA.
EM Briggsj@mail.nih.gov
RI Briggs, Josephine/B-9394-2009
OI Briggs, Josephine/0000-0003-0798-1190
FU NIDDK, NIH [HL 66242]; National Natural Science Foundation of China
[30770861]; Ministry of Human Resources of China
FX This work was supported by intramural funds from NIDDK, NIH grant HL
66242 (R.A.G.), and by the National Natural Science Foundation of China
(30770861) and Scientific Research Foundation for Excellent Returned
Scholars, Ministry of Human Resources of China (L.C.).
NR 35
TC 16
Z9 16
U1 1
U2 9
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD JUN
PY 2010
VL 21
IS 6
BP 986
EP 992
DI 10.1681/ASN.2009030307
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 606FW
UT WOS:000278409000016
PM 20395378
ER
PT J
AU Katki, HA
Sanders, CL
Graubard, BI
Bergen, AW
AF Katki, Hormuzd A.
Sanders, Christopher L.
Graubard, Barry I.
Bergen, Andrew W.
TI Using DNA Fingerprints to Infer Familial Relationships Within NHANES III
Households
SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
LA English
DT Article
DE Allele sharing; Combined DNA index system; Forensics; Identical by
descent; Identical by state; Population structure
ID BREAST-CANCER; RELATEDNESS; LOCI; INDIVIDUALS; POPULATIONS; GENOME;
ASSOCIATION; GENETICS; DATABASE; PAIRS
AB Developing, targeting, and evaluating genomic strategies for population-based disease prevention require population-based data. In response to this urgent need, genotyping has been conducted within the Third National Health and Nutrition Examination (NHANES III), a nationally representative household-interview health survey. However, before these genetic analyses can occur, family relationships within households must be accurately ascertained. Unfortunately, reported family relationships within NHANES III households based on questionnaire data are incomplete and inconclusive with regard to actual biological relatedness of family members. We inferred family relationships within households using DNA fingerprints (Identifiler (R)) that contain the DNA loci used by law enforcement agencies for forensic identification of individuals. The performance of these loci for relationship inference is not well understood, however. We evaluated two competing statistical methods for relationship inference on pairs of household members: an exact likelihood ratio relying on allele frequencies to an identical-by-state (IBS) likelihood ratio that only requires matching alleles. We modified these methods to account for genotyping errors and population substructure. The two methods usually agree on the rankings of the most likely relationships; however, the IBS method underestimates the likelihood ratio by not accounting for the informativeness of matching rare alleles. The likelihood ratio is sensitive to estimates of population substructure, and parent child relationships are sensitive to the specified genotyping error rate. These loci were unable to distinguish second-degree relationships and cousins from being unrelated. The genetic data also are useful for verifying reported relationships and identifying data quality issues. An important byproduct is the first explicitly nationally representative estimates of allele frequencies at these ubiquitous forensic loci.
C1 [Katki, Hormuzd A.; Graubard, Barry I.] Natl Canc Inst, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Sanders, Christopher L.] Medco Hlth Solut, Personalized Med Res Operat, Bethesda, MD 20814 USA.
[Bergen, Andrew W.] Stanford Res Int, Mol Genet Program, Menlo Pk, CA 94025 USA.
RP Katki, HA (reprint author), Natl Canc Inst, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
EM katkih@mail.nih.gov
RI Katki, Hormuzd/B-4003-2015;
OI Bergen, Andrew/0000-0002-1237-7644
FU National Institutes of Health/National Cancer Institute
FX Hormuzd A. Katki is Tenure-Track Principal Investigator, Biostatistics
Branch, Division of Cancer Epidemiology and Genetics, National Cancer
Institute, Rockville, MD 20852 (E-mail: katkih@mail.nih.gov).
Christopher L. Sanders is Director, Personalized Medicine Research
Operations, Medco Health Solutions, Bethesda, MD 20814. Barry I.
Graubard is Tenured Senior Investigator, Biostatistics Branch, Division
of Cancer Epidemiology and Genetics, National Cancer Institute,
Rockville, MD 20852. Andrew W. Bergen is Director, Molecular Genetics
Program, Stanford Research International, Menlo Park, CA 94025. The
authors thank the National Center for Health Statistics for the use of
their Research Data Center to conduct this research. This research was
supported in part by the Intramural Research Program of the National
Institutes of Health/National Cancer Institute. Conflict of Interest:
None declared.
NR 33
TC 6
Z9 6
U1 1
U2 5
PU AMER STATISTICAL ASSOC
PI ALEXANDRIA
PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA
SN 0162-1459
J9 J AM STAT ASSOC
JI J. Am. Stat. Assoc.
PD JUN
PY 2010
VL 105
IS 490
BP 552
EP 563
DI 10.1198/jasa.2010.ap09258
PG 12
WC Statistics & Probability
SC Mathematics
GA 629RF
UT WOS:000280216700009
PM 20664713
ER
PT J
AU Liu, AY
Li, QZ
Liu, CL
Yu, K
Yu, KF
AF Liu, Aiyi
Li, Qizhai
Liu, Chunling
Yu, Kai
Yu, Kai F.
TI A Rank-Based Test for Comparison of Multidimensional Outcomes
SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
LA English
DT Article
DE Autism spectrum disorder; Behrens-Fisher problem; Cardioprotective
solution; Case-control studies; Growth hormones; Multiple outcomes;
Nonparametrics; Rank-sum statistics
ID BEHRENS-FISHER PROBLEM; MULTIPLE END-POINTS; EXPONENTIAL DISTRIBUTION;
TRIALS
AB For comparison of multiple outcomes commonly encountered in biomedical research, Huang et al. (2005) improved O'Brien's (1984) rank-sum tests through the replacement of the ad hoc variance by the asymptotic variance of the test statistics. The improved tests control the type I error rate at the desired level and gain power when the differences between the two comparison groups in each outcome variable lie in the same direction; however, they may lose power when the differences are in different directions (e.g., some are positive and some are negative). These tests and the popular Bonferroni correction failed to show important significant differences when applied to compare heart rates from a clinical trial to evaluate the effect of a procedure to remove the cardioprotective solution HTK. We propose an alternative test statistic, taking the maximum of the individual rank-sum statistics, which controls the type I error rate and maintains satisfactory power regardless of the direction of the differences. Simulation studies show the proposed test to be of higher power than other tests in a certain alternative parameter space of interest. Furthermore, when used to analyze the heart rate data, the proposed test yields more satisfactory results.
C1 [Liu, Aiyi; Liu, Chunling; Yu, Kai F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD 20852 USA.
[Li, Qizhai] Chinese Acad Sci, Acad Math & Syst Sci, Key Lab Syst & Control, Beijing 100190, Peoples R China.
[Yu, Kai F.] Natl Canc Inst, Rockville, MD 20852 USA.
RP Liu, AY (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD 20852 USA.
EM liua@mail.nih.gov
RI Liu, Chunling/A-4827-2015;
OI Liu, Chunling/0000-0003-3410-445X; Liu, Aiyi/0000-0002-6618-5082
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; National Cancer Institute; National Young Science
Foundation of China [10901155]
FX Aiyi Liu is Senior Investigator, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, Rockville, MD 20852
(E-mail: liva@mail.nih.gov). Qizhai Li is Assistant Professor, Key
Laboratory of Systems and Control, Academy of Mathematics and Systems
Science, Chinese Academy of Sciences, Beijing, 100190, China. Chunling
Liu is Postdoctoral Fellow, Eunice Kennedy Shriver National Institute of
Child Health and Human Development, Rockville, MD 20852. Kai Yu is
Investigator, National Cancer Institute, Rockville, MD 20852. Kai F. Yu
is Senior Investigator, Eunice Kennedy Shriver National Institute of
Child Health and Human Development. This research was supported by the
Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development and the National Cancer
Institute. The research of Qizhai Li was partially supported by the
National Young Science Foundation of China (grant 10901155). The authors
thank two referees, an associate editor, and the editor for their
thoughtful comments and suggestions that improved the article, and Dr.
B. J. Stone for reading the manuscript.
NR 15
TC 9
Z9 10
U1 1
U2 3
PU AMER STATISTICAL ASSOC
PI ALEXANDRIA
PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA
SN 0162-1459
J9 J AM STAT ASSOC
JI J. Am. Stat. Assoc.
PD JUN
PY 2010
VL 105
IS 490
BP 578
EP 587
DI 10.1198/jasa.2010.ap09114
PG 10
WC Statistics & Probability
SC Mathematics
GA 629RF
UT WOS:000280216700011
PM 21625372
ER
PT J
AU Chatterjee, N
Li, Y
AF Chatterjee, Nilanjan
Li, Yan
TI Inference in Semiparametric Regression Models Under Partial
Questionnaire Design and Nonmonotone Missing Data
SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
LA English
DT Article
DE Mean score; Multiphase design; Outcome dependent sampling;
Pseudo-likelihood
ID MAXIMUM-LIKELIHOOD-ESTIMATION; NON-HODGKIN-LYMPHOMA; 2-STAGE
CASE-CONTROL; LOGISTIC-REGRESSION; COVARIATE DATA; PARAMETERS;
MULTISTAGE; EXPOSURE; 2-PHASE; DISEASE
AB In epidemiologic studies, partial questionnaire design (PQD) can reduce cost, time, and other practical burdens associated with lengthy questionnaires by assigning different subsets of the questionnaire to different, but overlapping, subsets of the study participants. In this article, we describe methods for semiparametric inference for regression model under PQD and other study settings that can generate nonmonotone missing data in covariates. In particular, motivated from methods for multiphase designs, we develop three estimators, namely mean score, pseudo-likelihood, and semiparametric maximum likelihood, each of which has some unique advantages. We develop the asymptotic theory and a sandwich variance estimator for each of the estimators under the underlying semiparametric model that allows the distribution of the covariates to remain nonparametric. We study the finite sample performances and relative efficiencies of the methods using simulation studies. We illustrate the methods using data from a case-control study of non-Hodgkin's lymphoma where the data on the main chemical exposures of interest are collected using two different instruments on two different, but overlapping, subsets of the participants. This article has supplementary material online.
C1 [Chatterjee, Nilanjan] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA.
[Li, Yan] Univ Texas Arlington, Dept Math, Arlington, TX 76019 USA.
RP Chatterjee, N (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA.
EM chattern@mail.nih.gov
FU National Cancer Institute (NCI), NIH, DHHS
FX Nilanjan Chatterjee is Senior Principal Investigator, Biostatistics
Branch, Division of Cancer Epidemiology and Genetics, National Cancer
Institute, NIH, DHHS, Rockville, MD 20852 (E-mail:
chattern@mail.nih.gov). Yan Li is Assistant Professor, Department of
Mathematics. University of Texas, Arlington, TX 76019. This research was
supported by the Intramural Research Program of the National Cancer
Institute (NCI), NIH, DHHS. The authors would like to thank Patricia
Flange and Joanne Colt at NCI for making the NHL data available for our
analysis.
NR 28
TC 1
Z9 1
U1 1
U2 1
PU AMER STATISTICAL ASSOC
PI ALEXANDRIA
PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA
SN 0162-1459
J9 J AM STAT ASSOC
JI J. Am. Stat. Assoc.
PD JUN
PY 2010
VL 105
IS 490
BP 787
EP 797
DI 10.1198/jasa.2010.tm08756
PG 11
WC Statistics & Probability
SC Mathematics
GA 629RF
UT WOS:000280216700029
ER
PT J
AU Holman, WL
Kirklin, JK
Naftel, DC
Kormos, RL
Desvign-Nickens, P
Camacho, MT
Ascheim, DD
AF Holman, William L.
Kirklin, James K.
Naftel, David C.
Kormos, Robert L.
Desvign-Nickens, Patricia
Camacho, Margarita T.
Ascheim, Deborah D.
TI Infection after implantation of pulsatile mechanical circulatory support
devices
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Article
ID VENTRICULAR ASSIST DEVICE; MULTICENTER CLINICAL-EVALUATION; AWAITING
HEART-TRANSPLANTATION; DESTINATION THERAPY; PATIENT SELECTION; REMATCH
TRIAL; EXPERIENCE; SYSTEM; OUTCOMES; FAILURE
AB Objective: INTERMACS is a registry of mechanical circulatory support devices sponsored by the National Institutes of Health. This analysis uses INTERMACS data to define the time course, incidence, and outcome of infection adverse events focusing on the first 3 months after implant.
Methods: Patients entered into INTERMACS from June 23, 2006, to September 30, 2008, were analyzed. Preimplant data (demographics, hemodynamics, and laboratory values), infection adverse events, and other outcomes were recorded. Infection adverse events were analyzed to compare infection rates in subgroups of patients and define risk factors for death.
Results: The analysis was confined to pulsatile mechanical circulatory support devices. A total of 593 patients from 88 institutions were entered. Infection was a relatively common event within the first 3 months of implant and was significantly (P - .005) more common in patients with biventricular assist devices than in patients with left ventricular assist devices, although the prevalence of infection equalized in months 4 to 12. Infection had a significant adverse effect on survival. Independent risk factors for death included support with a biventricular assist device, older age, severity of patient illness implantation of the device (INTERMACS level 1), and higher blood urea nitrogen.
Conclusions: Infection remains a relatively frequent adverse event and is associated with decreased survival. Interventions to prevent infection that focus on the preoperative and immediate postoperative periods are the ones most likely to achieve success by diminishing the incidence of infection during the initial 3 months after implantation. Rotary (continuous-flow) pumps are expected to have lower infection rates, but this remains to be seen. (J Thorac Cardiovasc Surg 2010;139:1632-6)
C1 [Holman, William L.; Kirklin, James K.; Naftel, David C.] Univ Alabama, Birmingham, AL USA.
[Kormos, Robert L.] Univ Pittsburgh, Pittsburgh, PA USA.
[Desvign-Nickens, Patricia] NHLBI, Rockville, MD USA.
[Camacho, Margarita T.] Newark Beth Israel Med Ctr, Newark, NJ USA.
[Ascheim, Deborah D.] Mt Sinai Sch Med, New York, NY USA.
RP Holman, WL (reprint author), Room 719 ZRB,703 19th St S, Birmingham, AL 35294 USA.
EM wholman@uab.edu
FU Thoratec
FX Margarita T. Camacho reports fees and grant support from Thoratec.
NR 22
TC 34
Z9 34
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5223
J9 J THORAC CARDIOV SUR
JI J. Thorac. Cardiovasc. Surg.
PD JUN
PY 2010
VL 139
IS 6
BP 1632
EP U309
DI 10.1016/j.jtcvs.2010.01.014
PG 7
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 599TX
UT WOS:000277937500040
PM 20363482
ER
PT J
AU Hollander, MC
Maier, CR
Linnoila, RI
Dennis, PA
AF Hollander, M. Christine
Maier, Colleen R.
Linnoila, R. Ilona
Dennis, Phillip A.
TI Selective requirement for Akt1 in mutant K-ras-mediated lung tumor
initiation and progression in mice
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Hollander, M. Christine; Maier, Colleen R.; Linnoila, R. Ilona; Dennis, Phillip A.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1556-0864
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD JUN
PY 2010
VL 5
IS 6
SU 3
BP S246
EP S246
PG 1
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 601XW
UT WOS:000278102300090
ER
PT J
AU Hong, JA
Zhang, M
Chinnasamy, N
Zhang, Y
Kunst, TF
Hancox, A
Mercedes, L
Kwong, K
Rosenberg, SA
Morgan, RA
Schrump, DS
AF Hong, Julie A.
Zhang, Mary
Chinnasamy, Nachimuthu
Zhang, Yuweii
Kunst, Tricia F.
Hancox, Ana
Mercedes, Leandro
Kwong, King
Rosenberg, Steven A.
Morgan, Richard A.
Schrump, David S.
TI Epigenetically modified autologous tumor cell vaccines: Potential
personalized immunotherapies targeting cancer-testis antigens in
thoracic malignancies
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Chinnasamy, Nachimuthu; Morgan, Richard A.] Natl Inst Hlth, Natl Canc Inst, Ctr Canc Res, Surg Branch,Immunotheraphy Sect, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 3
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1556-0864
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD JUN
PY 2010
VL 5
IS 6
SU 3
BP S257
EP S257
PG 1
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 601XW
UT WOS:000278102300122
ER
PT J
AU Komiya, T
Coxon, A
Park, Y
Chen, WD
Zajac-Kaye, M
Meltzer, P
Karpova, T
Kaye, FJ
AF Komiya, Takefumi
Coxon, Amy
Park, Yoonsoo
Chen, Wei-dong
Zajac-Kaye, Maria
Meltzer, Paul
Karpova, Tatiana
Kaye, Frederic J.
TI LKB1 regulates a novel CRTC1: CREB: NR4A2 pathway in lung cancer
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Komiya, Takefumi] Howard Univ Hosp, Washington, DC USA.
[Coxon, Amy; Park, Yoonsoo; Chen, Wei-dong; Meltzer, Paul; Karpova, Tatiana] NCI, Bethesda, MD 20892 USA.
[Zajac-Kaye, Maria; Kaye, Frederic J.] Univ Florida, Gainesville, FL USA.
RI kaye, frederic/E-2437-2011; CHEN, WEI-DONG/F-4521-2014
OI CHEN, WEI-DONG/0000-0003-2264-5515
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1556-0864
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD JUN
PY 2010
VL 5
IS 6
SU 3
BP S242
EP S243
PG 2
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 601XW
UT WOS:000278102300080
ER
PT J
AU Memmott, RM
Liewehr, DJ
Steinberg, SM
Hewitt, SM
Massion, PP
Dennis, PA
AF Memmott, Regan M.
Liewehr, David J.
Steinberg, Seth M.
Hewitt, Stephen M.
Massion, Pierre P.
Dennis, Phillip A.
TI Foxp3 expression in tumor-associated lymphocytes and epithelial cells is
associated with smoking status but not with survival of lung cancer
patients
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Memmott, Regan M.; Liewehr, David J.; Steinberg, Seth M.; Hewitt, Stephen M.; Dennis, Phillip A.] NCI, Bethesda, MD 20892 USA.
[Massion, Pierre P.] Vanderbilt Univ, Sch Med, Nashville, TN USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1556-0864
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD JUN
PY 2010
VL 5
IS 6
SU 3
BP S254
EP S254
PG 1
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 601XW
UT WOS:000278102300114
ER
PT J
AU Ryan, BM
Pine, SR
Robles, AI
Varticovski, L
Harris, CC
AF Ryan, Brid M.
Pine, Sharon R.
Robles, Ana I.
Varticovski, Lyuba
Harris, Curtis C.
TI Lung cancer cells asymmetrically divide their template DNA strands
during cell division
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Ryan, Brid M.; Pine, Sharon R.; Robles, Ana I.; Varticovski, Lyuba; Harris, Curtis C.] Natl Canc Inst, Human Carcinogenesis Lab, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1556-0864
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD JUN
PY 2010
VL 5
IS 6
SU 3
BP S222
EP S222
PG 1
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 601XW
UT WOS:000278102300021
ER
PT J
AU Voeller, D
Chen, M
Marguez, VE
Steeg, P
Kaye, FJ
Giaccone, G
Zajac-Kaye, M
AF Voeller, Donna
Chen, Min
Marguez, Victor E.
Steeg, Patricia
Kaye, Frederic J.
Giaccone, Giuseppe
Zajac-Kaye, Maria
TI Enhanced growth inhibition by combined methylation/HDAC inhibitors in
lung tumor cells with silenced CDKN2A
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Voeller, Donna; Chen, Min; Steeg, Patricia; Kaye, Frederic J.; Giaccone, Giuseppe; Zajac-Kaye, Maria] NCL, Bethesda, MD USA.
[Marguez, Victor E.] NCI, Frederick, MD USA.
RI kaye, frederic/E-2437-2011
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1556-0864
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD JUN
PY 2010
VL 5
IS 6
SU 3
BP S250
EP S250
PG 1
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 601XW
UT WOS:000278102300102
ER
PT J
AU Wang, XY
Jensen-Taubman, SM
Keefe, K
Linnoila, IR
AF Wang, Xiaoyang
Jensen-Taubman, Sandra M.
Keefe, Kathleen
Linnoila, Ilona R.
TI Human achaete-scute homolog-1 (hASH1) modulates tobacco-specific
nitrosamine (NNK)-induced lung tumorigenesis in mice
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Wang, Xiaoyang; Jensen-Taubman, Sandra M.; Keefe, Kathleen; Linnoila, Ilona R.] Natl Canc Ctr, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1556-0864
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD JUN
PY 2010
VL 5
IS 6
SU 3
BP S247
EP S247
PG 1
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 601XW
UT WOS:000278102300093
ER
PT J
AU Yan, WS
Shih, JH
Raso, G
Rodriguez-Canales, J
Behrens, C
Papadimitrakopoulou, VA
Herbst, RS
Emmert-Buck, MR
Wistuba, II
Erickson, HS
AF Yan, Wusheng
Shih, Joanna H.
Raso, Gabriela
Rodriguez-Canales, Jaime
Behrens, Carmen
Papadimitrakopoulou, Vali A.
Herbst, Roy S.
Emmert-Buck, Michael R.
Wistuba, Ignacio I.
Erickson, Heidi S.
TI Characterization of targeted-therapy-related molecular biomarkers from
NSCLC ever-smokers versus never-smokers by a novel qRT-PCR for
microdissected tissues methodology
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Meeting Abstract
C1 [Yan, Wusheng; Shih, Joanna H.; Rodriguez-Canales, Jaime; Emmert-Buck, Michael R.] NCI, Gaithersburg, MD USA.
[Raso, Gabriela; Behrens, Carmen; Papadimitrakopoulou, Vali A.; Herbst, Roy S.; Wistuba, Ignacio I.; Erickson, Heidi S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1556-0864
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD JUN
PY 2010
VL 5
IS 6
SU 3
BP S237
EP S237
PG 1
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 601XW
UT WOS:000278102300064
ER
PT J
AU Su, J
Cui, X
Li, Y
Mani, H
Ferreyra, GA
Danner, RL
Hsu, LL
Fitz, Y
Eichacker, PQ
AF Su, Junwu
Cui, Xizhong
Li, Yan
Mani, Haresh
Ferreyra, Gabriela A.
Danner, Robert L.
Hsu, Lewis L.
Fitz, Yvonne
Eichacker, Peter Q.
TI SB203580, a p38 Inhibitor, Improved Cardiac Function but Worsened Lung
Injury and Survival During Escherichia coli Pneumonia in Mice
SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE
LA English
DT Article
DE p38 MAP kinase inhibitor; Treatment; Sepsis; Pneumonia; Cardiopulmonary
dysfunction
ID ACTIVATED PROTEIN-KINASE; TUMOR-NECROSIS-FACTOR; TOLL-LIKE RECEPTOR;
MURINE MODEL; PULMONARY INFLAMMATION; POLYMICROBIAL SEPSIS; HUMAN
MACROPHAGES; FACTOR-ALPHA; MAP KINASES; KAPPA-B
AB Background: Supporting its therapeutic application in sepsis, p38 mitogen-activated protein kinase ( MAPK) inhibition decreases cardiopulmonary injury and lethality with lipopolysaccharide challenge. However, only one preclinical study has reported the survival effects of a p38 inhibitor ( SB203580, 100 mg/kg) during infection. We therefore tested SB203580 in mice ( n = 763) challenged with intratracheal Escherichia coli and treated with antibiotics and fluids.
Methods and Results: Compared with placebo, high dose SB203580 ( 100 mg/kg) pretreatment increased the hazards ratio of death ( 95% confidence interval) ( 3.6 [ 2.1, 6.1], p < 0.0001). Decreasing doses ( 10, 1, or 0.1 mg/kg) went from being harmful to having no significant effect ( p < 0.0001 for the effect of decreasing dose). At 48 hours, but not 24 hours after E. coli, high and low dose SB203580 pretreatment decreased cardiac phosphorylated p38 MAPK levels and improved cardiac output either ( p <= 0.07). Low dose SB203580 did not alter lung neutrophils significantly but increased lung injury at 48 hours ( p = 0.05). High dose decreased lung neutrophils and injury at 24 hours ( p = 0.09 and 0.01, respectively) but then increased them at 48 hours ( both p <= 0.01). Lung injury was greater with high versus low dose at 48 hours ( p = 0.002).
Conclusion: Thus, SB203580 had divergent effects on cardiac and lung function in E. coli challenged mice. Furthermore, high dose worsened survival and low dose did not improve it. Altogether, these findings suggest that clearly defining the risks and benefits of p38 MAPK inhibition is important before such treatment is applied in patients with or at risk of serious infection.
C1 [Su, Junwu; Cui, Xizhong; Li, Yan; Ferreyra, Gabriela A.; Danner, Robert L.; Fitz, Yvonne; Eichacker, Peter Q.] NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Su, Junwu] Capital Med Univ, Anzhen Hosp, Surg Dept Pediat Cardiol, Beijing, Peoples R China.
[Mani, Haresh] NCI, Dept Pathol, Bethesda, MD 20892 USA.
[Hsu, Lewis L.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Eichacker, PQ (reprint author), NIH, Ctr Clin, Dept Crit Care Med, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM peichacker@mail.cc.nih.gov
FU NIH
FX Supported by NIH intramural funds.
NR 52
TC 8
Z9 10
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-5282
J9 J TRAUMA
JI J. Trauma-Injury Infect. Crit. Care
PD JUN
PY 2010
VL 68
IS 6
BP 1317
EP 1327
DI 10.1097/TA.0b013e3181bb9cd3
PG 11
WC Critical Care Medicine; Surgery
SC General & Internal Medicine; Surgery
GA 610ES
UT WOS:000278714600010
PM 20068480
ER
PT J
AU Figg, WD
Woo, S
Zhu, WH
Chen, XH
Ajiboye, AS
Steinberg, SM
Price, DK
Wright, JJ
Parnes, HL
Arlen, PM
Gulley, JL
Dahut, WL
AF Figg, William D.
Woo, Sukyung
Zhu, Wenhui
Chen, Xiaohong
Ajiboye, A. Seun
Steinberg, Seth M.
Price, Douglas K.
Wright, John J.
Parnes, Howard L.
Arlen, Philip M.
Gulley, James L.
Dahut, William L.
TI A Phase I Clinical Study of High Dose Ketoconazole Plus Weekly Docetaxel
for Metastatic Castration Resistant Prostate Cancer
SO JOURNAL OF UROLOGY
LA English
DT Article
DE prostatic neoplasms; docetaxel; ketoconazole; drug interactions
ID PHARMACOKINETICS; MITOXANTRONE; PREDNISONE; SURVIVAL; THERAPY; FUTURE;
TRIAL
AB Purpose: This phase I study of high dose ketoconazole and docetaxel was designed against castration resistant prostate cancer to determine the maximum tolerated doses, side effects, and pharmacokinetic interaction of co-administered docetaxel and ketoconazole.
Materials and Methods: Patients with metastatic castration resistant prostate cancer received weekly docetaxel for 3 of every 4 weeks plus daily ketoconazole. Pharmacokinetic studies were performed on day 1 (docetaxel alone) and day 16 (after ketoconazole).
Results: The study enrolled 42 patients at 9 different dose levels. The combination regimens investigated included docetaxel weekly, increasing from 5 to 43 mg/m(2), with starting doses of 600, 800 or 1,200 mg ketoconazole daily. Decreases in prostate specific antigen of 50% or greater were seen in 62% of patients. Of 25 patients with soft tissue disease 7 (28%) had a partial response. Median overall survival was 22.8 months and was significantly greater in docetaxel naive patients than in patients pretreated with docetaxel (36.8 vs 10.3 months, p = 0.0001). The most frequently observed adverse events were anemia, edema, fatigue, diarrhea, nausea, sensory neuropathy and elevated liver function tests. The fractional change in docetaxel clearance correlated significantly with ketoconazole exposure (p <0.01). Concomitant ketoconazole increased docetaxel exposure 2.6-fold with 1,200 mg daily, 1.6-fold with 800 mg daily and approximately 1.3 to 1.5-fold with 600 mg daily.
Conclusions: Combination regimens using 600 mg ketoconazole daily were fairly well tolerated and the maximum tolerated dose of docetaxel was 32 mg/m2. Results suggest that the combination has significant antitumor activity in castration resistant prostate cancer. The long survival in the docetaxel naive cohort warrants additional, larger trials of docetaxel with ketoconazole or possibly CYP17A1 inhibitors such as abiraterone.
C1 [Figg, William D.; Zhu, Wenhui; Arlen, Philip M.; Gulley, James L.; Dahut, William L.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Figg, William D.; Woo, Sukyung; Chen, Xiaohong] NCI, Clin Pharmacol Program, NIH, Bethesda, MD 20892 USA.
[Figg, William D.; Ajiboye, A. Seun; Price, Douglas K.] NCI, Mol Pharmacol Sect, NIH, Bethesda, MD 20892 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Wright, John J.] NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Parnes, Howard L.] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
RP Figg, WD (reprint author), NCI, Med Oncol Branch, NIH, Bldg 10,Room 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM wdfigg@helix.nih.gov
RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016
OI Gulley, James/0000-0002-6569-2912;
FU Center for Cancer Research; National Cancer Institute, National
Institutes of Health
FX Supported by the Intramural Research Program of the Center for Cancer
Research, National Cancer Institute, National Institutes of Health. The
results and discussions presented herein do not represent the views of
these federal agencies.
NR 25
TC 17
Z9 17
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
J9 J UROLOGY
JI J. Urol.
PD JUN
PY 2010
VL 183
IS 6
BP 2219
EP 2226
DI 10.1016/j.juro.2010.02.020
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 595QZ
UT WOS:000277628700031
PM 20399458
ER
PT J
AU Sharma, KV
Dreher, MR
Tang, YQ
Pritchard, W
Chiesa, OA
Karanian, J
Peregoy, J
Orandi, B
Woods, D
Donahue, D
Esparza, J
Jones, G
Willis, SL
Lewis, AL
Wood, BJ
AF Sharma, Karun V.
Dreher, Matthew R.
Tang, Yiqing
Pritchard, William
Chiesa, Oscar A.
Karanian, John
Peregoy, Jennifer
Orandi, Babak
Woods, David
Donahue, Danielle
Esparza, Juan
Jones, Guy
Willis, Sean L.
Lewis, Andrew L.
Wood, Bradford J.
TI Development of "Imageable" Beads for Transcatheter Embolotherapy
SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
LA English
DT Article
ID DOXORUBICIN-ELUTING BEADS; UNRESECTABLE HEPATOCELLULAR-CARCINOMA;
UTERINE ARTERY EMBOLIZATION; TRANSARTERIAL CHEMOEMBOLIZATION;
LIVER-CANCER; OILY CHEMOEMBOLIZATION; SURVIVAL RATES; ANIMAL-MODEL; DC
BEAD; MICROSPHERES
AB PURPOSE: To develop and characterize radiopaque embolization microspheres capable of in vivo detection with intraprocedural fluoroscopy and computed tomography (CT) imaging and to evaluate their spatial distribution inside target tissues during and after transcatheter embolization.
MATERIALS AND METHODS: Polyvinyl alcohol hydrogel microspheres were loaded with Lipiodol and examined for iodine content, stability of loading, and conspicuity with fluoroscopy and CT in vitro. Transcatheter embolization of swine liver and kidney was performed with the radiopaque microspheres and spatial distribution was evaluated with intraprocedural fluoroscopy and CT. Ex vivo evaluation was performed with light microscopy and micro-CT.
RESULTS: In vitro analyses demonstrated that radiopaque microspheres could be loaded with sufficient iodine content to be detected with routine fluoroscopy and CT imaging and that such loading was relatively stable. Radiopaque microspheres were visible in vivo with fluoroscopy and CT during transcatheter embolization. CT imaging during embolization procedures demonstrated a dose-dependent relationship in the number and size of visualized embolized arteries. Imaging features of radiopaque microsphere distribution inside target tissues correlated well with ex vivo light microscopic and micro-CT evaluation of microsphere distribution.
CONCLUSIONS: Radiopaque embolization microspheres are visualized during transcatheter embolization with routine intraprocedural fluoroscopy and CT. These radiopaque microspheres provided the three-dimensional spatial distribution of embolic material inside target organs during the procedure, and therefore can provide real-time intraprocedural feedback for the interventional radiologist. These microspheres may be useful for demonstrating the influence of material and technical variability in transcatheter embolization in addition to providing intraprocedural identification of tissue at risk of undertreatment.
C1 [Sharma, Karun V.; Dreher, Matthew R.; Orandi, Babak; Woods, David; Donahue, Danielle; Jones, Guy; Wood, Bradford J.] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
[Pritchard, William; Chiesa, Oscar A.; Karanian, John; Peregoy, Jennifer; Esparza, Juan] US FDA, Ctr Devices & Radiol Hlth, Laurel, MD USA.
[Sharma, Karun V.] Georgetown Univ Hosp, Dept Radiol, Washington, DC 20007 USA.
[Tang, Yiqing; Willis, Sean L.; Lewis, Andrew L.] Biocompatibles UK, Farnham, Surrey, England.
RP Wood, BJ (reprint author), NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM BWood@cc.nih.gov
OI Lewis, Andrew/0000-0001-5779-5631
FU Society of Interventional Radiology Foundation Ring; NIH
FX The Society of Interventional Radiology Foundation Ring Grant was
awarded to K.V.S. This study was conducted in the National Institutes of
Health (NIH) Center for Interventional Oncology and was supported in
part by the Intramural Research Program of NIH, a Society of
Interventional Radiology Foundation Ring Grant, and an Interagency
Agreement between the NIH and the United States Food and Drug
Administration (FDA). NIH and Biocompatibles UK (Farnham, United
Kingdom) have a Cooperative Research and Development Agreement. The
mention of commercial products, their source, or their use in connection
with material reported herein is not to be construed as an actual or
implied endorsement of such products by the FDA, NIH, Department of
Health and Human Services, or Public Health Service.
NR 38
TC 41
Z9 44
U1 3
U2 16
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1051-0443
J9 J VASC INTERV RADIOL
JI J. Vasc. Interv. Radiol.
PD JUN
PY 2010
VL 21
IS 6
BP 865
EP 876
DI 10.1016/j.jvir.2010.02.031
PG 12
WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular
Disease
SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System &
Cardiology
GA 607SY
UT WOS:000278528100014
PM 20494290
ER
PT J
AU Abi-Jaoudeh, N
Glossop, N
Dake, M
Pritchard, WF
Chiesa, A
Dreher, MR
Tang, T
Karanian, JW
Wood, BJ
AF Abi-Jaoudeh, Nadine
Glossop, Neil
Dake, Michael
Pritchard, William F.
Chiesa, Alberto
Dreher, Matthew R.
Tang, Thomas
Karanian, John W.
Wood, Bradford J.
TI Electromagnetic Navigation for Thoracic Aortic Stent-graft Deployment: A
Pilot Study in Swine
SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
LA English
DT Article
ID LEFT SUBCLAVIAN ARTERY; ENDOVASCULAR REPAIR; TRACKING; RUPTURE;
FEASIBILITY; MANAGEMENT; CT
AB PURPOSE: To determine the feasibility of electromagnetic tracking as a method to augment conventional imaging guidance for the safe delivery, precise positioning, and accurate deployment of thoracic aortic endografts.
MATERIALS AND METHODS: Custom guide wires were fabricated, and the delivery catheters for thoracic aortic endoprostheses were retrofitted with integrated electromagnetic coil sensors to enable real-time endovascular tracking. Preprocedure thoracic computed tomographic (CT) angiograms were obtained after the placement of fiducial skin patches on the chest wall of three anesthetized swine, enabling automatic registration. The stent-graft deployment location target near the subclavian artery was selected on the preprocedure CT angiogram. Two steps were analyzed: advancing a tracked glidewire to the aortic arch and positioning the tracked stent-graft assembly by using electromagnetic guidance alone. Multiple CT scans were obtained to evaluate the accuracy of the electromagnetic tracking system by measuring the target registration error, which compared the actual position of the tracked devices to the displayed "virtual" electromagnetic-tracked position. Postdeployment CT angiography and necropsy helped confirm stent-graft position and subclavian artery patency.
RESULTS: A stent-graft was successfully delivered and deployed in each of the three animals by using real-time electromagnetic tracking alone. The mean fiducial registration error with autoregistration was 1.5 mm. Sixteen comparative scans were obtained to determine the target registration error, which was 4.3 mm +/- 0.97 (range, 3.0-6.0 mm) for the glidewire sensor coil. The mean target registration error for the stent-graft delivery catheter sensor coil was 2.6 mm +/- 0.7 (range, 1.9-3.8 mm). The mean deployment error for the stent-graft, defined as deployment deviation from the target, was 2.6 mm +/- 3.0.
CONCLUSIONS: Delivery and deployment of customized thoracic stent-grafts with use of electromagnetic tracking alone is feasible and accurate in swine. Combining endovascular electromagnetic tracking with conventional fluoroscopy may further improve accuracy and be a more realistic multimodality approach.
C1 [Abi-Jaoudeh, Nadine; Dreher, Matthew R.; Wood, Bradford J.] NIH, Dept Radiol & Imaging Sci, Bethesda, MD 20890 USA.
[Pritchard, William F.; Chiesa, Alberto; Karanian, John W.] US FDA, Ctr Devices & Radiol Hlth, Lab Cardiovasc & Intervent Therapeut, Laurel, MD USA.
[Dake, Michael] Stanford Univ, Dept Cardiothorac Surg, Stanford, CA 94305 USA.
[Glossop, Neil; Tang, Thomas] Traxtal Inc, Toronto, ON, Canada.
RP Abi-Jaoudeh, N (reprint author), NIH, Dept Radiol & Imaging Sci, Rm 1C365,MSC 1182,10 Ctr Dr,9000 Rockville Pike, Bethesda, MD 20890 USA.
EM naj@mail.nih.gov
FU National Institutes of Health
FX N.G. is a salaried employee of Traxtal Inc, a Philips Healthcare
Company, Intellectual Property in the field. M.D. is a member and paid
consultant of the Endovascular Scientific Advisory Board, W. L. Gore and
Associates. T.T. is a salaried employee of Traxtal Inc, a Philips
Healthcare Company. B.J.W. has a Cooperative Research and Development
Agreement with Philips, Intellectual Property in the field. None of the
other authors have identified a conflict of interest. This work is
supported in part by the Intramural Research Program of the National
Institutes of Health. This project is a collaboration between the
National Institutes of Health and the Food and Drug Administration as
part of an interagency agreement.
NR 27
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Z9 25
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1051-0443
J9 J VASC INTERV RADIOL
JI J. Vasc. Interv. Radiol.
PD JUN
PY 2010
VL 21
IS 6
BP 888
EP 895
DI 10.1016/j.jvir.2009.12.402
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular
Disease
SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System &
Cardiology
GA 607SY
UT WOS:000278528100017
PM 20382032
ER
PT J
AU Julg, B
Williams, KL
Reddy, S
Bishop, K
Qi, Y
Carrington, M
Goulder, PJ
Ndung'u, T
Walker, BD
AF Julg, B.
Williams, K. L.
Reddy, S.
Bishop, K.
Qi, Y.
Carrington, M.
Goulder, P. J.
Ndung'u, T.
Walker, B. D.
TI Enhanced Anti-HIV Functional Activity Associated with Gag-Specific CD8
T-Cell Responses
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; VIRAL LOAD; TYPE-1 REPLICATION; IMMUNE
CONTROL; EX-VIVO; LYMPHOCYTES; INFECTION; HLA; EXPRESSION; PROTEINS
AB Effective HIV-specific T-cell immunity requires the ability to inhibit virus replication in the infected host, but the functional characteristics of cells able to mediate this effect are not well defined. Since Gag-specific CD8 T cells have repeatedly been associated with lower viremia, we examined the influence of Gag specificity on the ability of unstimulated CD8 T cells from chronically infected persons to inhibit virus replication in autologous CD4 T cells. Persons with broad (>= 6; n = 13) or narrow (<= 1; n = 13) Gag-specific responses, as assessed by gamma interferon enzyme-linked immunospot assay, were selected from 288 highly active antiretroviral therapy (HAART)-naive HIV-1 clade C-infected South Africans, matching groups for total magnitude of HIV-specific CD8 T-cell responses and CD4 T-cell counts. CD8 T cells from high Gag responders suppressed in vitro replication of a heterologous HIV strain in autologous CD4 cells more potently than did those from low Gag responders (P < 0.003) and were associated with lower viral loads in vivo (P < 0.002). As previously shown in subjects with low viremia, CD8 T cells from high Gag responders exhibited a more polyfunctional cytokine profile and a stronger ability to proliferate in response to HIV stimulation than did low Gag responders, which mainly exhibited monofunctional CD8 T-cell responses. Furthermore, increased polyfunctionality was significantly correlated with greater inhibition of viral replication in vitro. These data indicate that enhanced suppression of HIV replication is associated with broader targeting of Gag. We conclude that it is not the overall magnitude but rather the breadth, magnitude, and functional capacity of CD8 T-cell responses to certain conserved proteins, like Gag, which predict effective antiviral HIV-specific CD8 T-cell function.
C1 [Julg, B.; Williams, K. L.; Reddy, S.; Bishop, K.; Goulder, P. J.; Ndung'u, T.; Walker, B. D.] Univ KwaZulu Natal, HIV Pathogenesis Program, Doris Duke Med Res Inst, Durban, South Africa.
[Julg, B.; Williams, K. L.; Reddy, S.; Bishop, K.; Goulder, P. J.; Ndung'u, T.; Walker, B. D.] Univ KwaZulu Natal, KwaZulu Natal Res Inst TB & HIV, Durban, South Africa.
[Julg, B.; Williams, K. L.; Carrington, M.; Goulder, P. J.; Ndung'u, T.; Walker, B. D.] MIT & Harvard, Ragon Inst MGH, Boston, MA USA.
[Qi, Y.; Carrington, M.] NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Goulder, P. J.] Univ Oxford, Dept Pediat, Oxford, England.
[Walker, B. D.] Howard Hughes Med Inst, Chevy Chase, MD USA.
RP Walker, BD (reprint author), MIT & Harvard, Ragon Inst MGH, 149 13th St, Charlestown, MA 02129 USA.
EM bwalker@partners.org
OI Bishop, Karen/0000-0003-4935-7708; Ndung'u, Thumbi/0000-0003-2962-3992
FU Bill and Melinda Gates Foundation; Mark and Lisa Schwartz Foundation;
DDCF; CFAR; Wellcome Trust; [RO1 AI30914]; [RO1 AI28568]; [AI046995]
FX B. D. W. received funding from grants RO1 AI30914 and AI28568, the Bill
and Melinda Gates Foundation, Mark and Lisa Schwartz Foundation, DDCF,
and CFAR. P.J.G. is funded by the Wellcome Trust and grant AI046995.
T.N. holds the South African DST/NRF Chair in Systems Biology of
HIV/AIDS.
NR 34
TC 58
Z9 59
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD JUN
PY 2010
VL 84
IS 11
BP 5540
EP 5549
DI 10.1128/JVI.02031-09
PG 10
WC Virology
SC Virology
GA 592NQ
UT WOS:000277386700009
PM 20335261
ER
PT J
AU Ghedin, E
Wentworth, DE
Halpin, RA
Lin, XD
Bera, J
DePasse, J
Fitch, A
Griesemer, S
Hine, E
Katzel, DA
Overton, L
Proudfoot, K
Sitz, J
Szczypinski, B
St George, K
Spiro, DJ
Holmes, EC
AF Ghedin, Elodie
Wentworth, David E.
Halpin, Rebecca A.
Lin, Xudong
Bera, Jayati
DePasse, Jay
Fitch, Adam
Griesemer, Sara
Hine, Erin
Katzel, Daniel A.
Overton, Larry
Proudfoot, Kathleen
Sitz, Jeffrey
Szczypinski, Bridget
St George, Kirsten
Spiro, David J.
Holmes, Edward C.
TI Unseasonal Transmission of H3N2 Influenza A Virus During the
Swine-Origin H1N1 Pandemic
SO JOURNAL OF VIROLOGY
LA English
DT Article
AB The initial wave of swine-origin influenza A virus (pandemic H1N1/09) in the United States during the spring and summer of 2009 also resulted in an increased vigilance and sampling of seasonal influenza viruses (H1N1 and H3N2), even though they are normally characterized by very low incidence outside of the winter months. To explore the nature of virus evolution during this influenza "off-season," we conducted a phylogenetic analysis of H1N1 and H3N2 sequences sampled during April to June 2009 in New York State. Our analysis revealed that multiple lineages of both viruses were introduced and cocirculated during this time, as is typical of influenza virus during the winter. Strikingly, however, we also found strong evidence for the presence of a large transmission chain of H3N2 viruses centered on the south-east of New York State and which continued until at least 1 June 2009. These results suggest that the unseasonal transmission of influenza A viruses may be more widespread than is usually supposed.
C1 [Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Ghedin, Elodie; DePasse, Jay; Fitch, Adam] Univ Pittsburgh, Sch Med, Dept Computat Biol, Ctr Vaccine Res, Pittsburgh, PA 15261 USA.
[Wentworth, David E.; Lin, Xudong; Griesemer, Sara; St George, Kirsten] NYSDH, Wadsworth Ctr, Albany, NY 12201 USA.
[Wentworth, David E.] SUNY Albany, Sch Publ Hlth, Albany, NY 12201 USA.
[Halpin, Rebecca A.; Bera, Jayati; Hine, Erin; Katzel, Daniel A.; Overton, Larry; Proudfoot, Kathleen; Sitz, Jeffrey; Szczypinski, Bridget; Spiro, David J.] J Craig Venter Inst, Rockville, MD 20850 USA.
RP Holmes, EC (reprint author), Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
EM ech15@psu.edu
OI Wentworth, David/0000-0002-5190-980X; Holmes, Edward/0000-0001-9596-3552
FU NIH [GM080533, HHSN272200900007C]; NIH/NIAID [P01 AI059576-05]; New York
State Department of Health
FX This study was in part funded by NIH grant GM080533 and NIH contract
HHSN272200900007C. D. E. W. is funded in part by NIH/NIAID P01
AI059576-05 and the New York State Department of Health. K. S. G. is
supported in part by the New York State Department of Health.
NR 16
TC 10
Z9 10
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD JUN
PY 2010
VL 84
IS 11
BP 5715
EP 5718
DI 10.1128/JVI.00018-10
PG 4
WC Virology
SC Virology
GA 592NQ
UT WOS:000277386700025
PM 20237080
ER
PT J
AU Paprotka, T
Venkatachari, NJ
Chaipan, C
Burdick, R
Delviks-Frankenberry, KA
Hu, WS
Pathak, VK
AF Paprotka, Tobias
Venkatachari, Narasimhan J.
Chaipan, Chawaree
Burdick, Ryan
Delviks-Frankenberry, Krista A.
Hu, Wei-Shau
Pathak, Vinay K.
TI Inhibition of Xenotropic Murine Leukemia Virus-Related Virus by APOBEC3
Proteins and Antiviral Drugs
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CHRONIC-FATIGUE-SYNDROME; PROSTATE
CARCINOMA-CELLS; HIV-1 INFECTION; RETROVIRAL RESTRICTION;
GAMMARETROVIRUS XMRV; CYTIDINE DEAMINASES; DENDRITIC CELLS; VIF PROTEIN;
IN-VIVO
AB Xenotropic murine leukemia virus-related virus (XMRV), a gammaretrovirus, has been isolated from human prostate cancer tissue and from activated CD4(+) T cells and B cells of patients with chronic fatigue syndrome, suggesting an association between XMRV infection and these two diseases. Since APOBEC3G (A3G) and APOBEC3F (A3F), which are potent inhibitors of murine leukemia virus and Vif-deficient human immunodeficiency virus type 1 (HIV-1), are expressed in human CD4(+) T cells and B cells, we sought to determine how XMRV evades suppression of replication by APOBEC3 proteins. We found that expression of A3G, A3F, or murine A3 in virus-producing cells resulted in their virion incorporation, inhibition of XMRV replication, and G-to-A hypermutation of the viral DNA with all three APOBEC3 proteins. Quantitation of A3G and A3F mRNAs indicated that, compared to the human T-cell lines CEM and H9, prostate cell lines LNCaP and DU145 exhibited 50% lower A3F mRNA levels, whereas A3G expression in 22Rv1, LNCaP, and DU145 cells was nearly undetectable. XMRV proviral genomes in LNCaP and DU145 cells were hypermutated at low frequency with mutation patterns consistent with A3F activity. XMRV proviral genomes were extensively hypermutated upon replication in A3G/A3F-positive T cells (CEM and H9), but not in A3G/A3F-negative cells (CEM-SS). We also observed that XMRV replication was susceptible to the nucleoside reverse transcriptase (RT) inhibitors zidovudine (AZT) and tenofovir and the integrase inhibitor raltegravir. In summary, the establishment of XMRV infection in patients may be dependent on infection of A3G/A3F-deficient cells, and cells expressing low levels of A3G/A3F, such as prostate cancer cells, may be ideal producers of infectious XMRV. Furthermore, the anti-HIV-1 drugs AZT, tenofovir, and raltegravir may be useful for treatment of XMRV infection.
C1 [Paprotka, Tobias; Venkatachari, Narasimhan J.; Chaipan, Chawaree; Burdick, Ryan; Delviks-Frankenberry, Krista A.; Pathak, Vinay K.] NCI, Viral Mutat Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA.
[Hu, Wei-Shau] NCI, Viral Recombinat Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA.
RP Pathak, VK (reprint author), NCI, Viral Mutat Sect, HIV Drug Resistance Program, POB B,Bldg 535,Room 334, Frederick, MD 21702 USA.
EM vinay.pathak@nih.gov
RI Delviks-Frankenberry, Krista/M-4822-2013
FU NIH, National Cancer Institute, Center for Cancer Research
FX This research was supported in part by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research.
NR 69
TC 61
Z9 63
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD JUN
PY 2010
VL 84
IS 11
BP 5719
EP 5729
DI 10.1128/JVI.00134-10
PG 11
WC Virology
SC Virology
GA 592NQ
UT WOS:000277386700026
PM 20335265
ER
PT J
AU Rosario, M
Hopkins, R
Fulkerson, J
Borthwick, N
Quigley, MF
Joseph, J
Douek, DC
Greenaway, HY
Venturi, V
Gostick, E
Price, DA
Both, GW
Sadoff, JC
Hanke, T
AF Rosario, Maximillian
Hopkins, Richard
Fulkerson, John
Borthwick, Nicola
Quigley, Maire F.
Joseph, Joan
Douek, Daniel C.
Greenaway, Hui Yee
Venturi, Vanessa
Gostick, Emma
Price, David A.
Both, Gerald W.
Sadoff, Jerald C.
Hanke, Tomas
TI Novel Recombinant Mycobacterium bovis BCG, Ovine Atadenovirus, and
Modified Vaccinia Virus Ankara Vaccines Combine To Induce Robust Human
Immunodeficiency Virus-Specific CD4 and CD8 T-Cell Responses in Rhesus
Macaques
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID BACILLE CALMETTE-GUERIN; ACTIVE ANTIRETROVIRAL THERAPY; CLADE-A VACCINE;
HIV-1 VACCINE; BOOST VACCINATION; ENHANCED IMMUNOGENICITY; PROTECTIVE
EFFICACY; CLINICAL-TRIALS; LYMPHOCYTES-T; SIV INFECTION
AB Mycobacterium bovis bacillus Calmette-Guerin (BCG), which elicits a degree of protective immunity against tuberculosis, is the most widely used vaccine in the world. Due to its persistence and immunogenicity, BCG has been proposed as a vector for vaccines against other infections, including HIV-1. BCG has a very good safety record, although it can cause disseminated disease in immunocompromised individuals. Here, we constructed a recombinant BCG vector expressing HIV-1 clade A-derived immunogen HIVA using the recently described safer and more immunogenic BCG strain AERAS-401 as the parental mycobacterium. Using routine ex vivo T-cell assays, BCG.HIVA(401) as a stand-alone vaccine induced undetectable and weak CD8 T-cell responses in BALB/c mice and rhesus macaques, respectively. However, when BCG.HIVA(401) was used as a priming component in heterologous vaccination regimens together with recombinant modified vaccinia virus Ankara-vectored MVA.HIVA and ovine atadenovirus-vectored OAdV.HIVA vaccines, robust HIV-1-specific T-cell responses were elicited. These high-frequency T-cell responses were broadly directed and capable of proliferation in response to recall antigen. Furthermore, multiple antigen-specific T-cell clonotypes were efficiently recruited into the memory pool. These desirable features are thought to be associated with good control of HIV-1 infection. In addition, strong and persistent T-cell responses specific for the BCG-derived purified protein derivative (PPD) antigen were induced. This work is the first demonstration of immunogenicity for two novel vaccine vectors and the corresponding candidate HIV-1 vaccines BCG.HIVA(401) and OAdV.HIVA in nonhuman primates. These results strongly support their further exploration.
C1 [Rosario, Maximillian; Hopkins, Richard; Borthwick, Nicola; Hanke, Tomas] Univ Oxford, MRC Human Immunol Unit, Weatherall Inst Mol Med, Oxford OX3 9DS, England.
[Fulkerson, John; Sadoff, Jerald C.] Aeras Global TB Vaccine Fdn, Rockville, MD 20850 USA.
[Quigley, Maire F.; Douek, Daniel C.; Price, David A.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Joseph, Joan] Univ Barcelona, Catalan HIV Vaccine Res & Dev Ctr, August Pi Sunyer Biomed Res Inst, AIDS Res Unit,Infect Dis Dept,Hosp Clin,Sch Med, E-08036 Barcelona, Spain.
[Greenaway, Hui Yee; Venturi, Vanessa] Univ New S Wales, Computat Biol Unit, Ctr Vasc Res, Kensington, NSW 2052, Australia.
[Gostick, Emma; Price, David A.] Cardiff Univ, Dept Med Biochem & Immunol, Sch Med, Cardiff CF14 4XN, S Glam, Wales.
[Both, Gerald W.] Biotech Equity Partners Pty Ltd, N Ryde, NSW 2113, Australia.
RP Hanke, T (reprint author), Univ Oxford, MRC Human Immunol Unit, Weatherall Inst Mol Med, Oxford OX3 9DS, England.
EM tomas.hanke@imm.ox.ac.uk
RI Price, David/C-7876-2013
OI Price, David/0000-0001-9416-2737
FU Medical Research Council (United Kingdom); Australian Research Council
(ARC) [DP0452362]; Spanish Research Council; Foundation for Research and
Prevention of AIDS in Spain [FIPSE 36338/02]; Fundacion Mutua Madrilena
de Automoviles; Fundacio BCN SIDA 2002; National Institute of Allergy
and Infectious Diseases, National Institutes of Health (United States)
FX This work was supported by the Medical Research Council (United
Kingdom); the Australian Research Council (ARC; DP0452362); the Spanish
Research Council; the Foundation for Research and Prevention of AIDS in
Spain (FIPSE 36338/02); the Fundacion Mutua Madrilena de Automoviles
(second call for proposals); Fundacio BCN SIDA 2002; and the Intramural
Research Program of the Vaccine Research Center, National Institute of
Allergy and Infectious Diseases, National Institutes of Health (United
States). D. A. P. is a Medical Research Council (United Kingdom) Senior
Clinical Fellow, T. H. is a Jenner Institute Investigator, V. V. is an
ARC Future Fellow, and M. F. Q. is a Marie Curie International Outgoing
Research Fellow.
NR 67
TC 13
Z9 14
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD JUN
PY 2010
VL 84
IS 12
BP 5898
EP 5908
DI 10.1128/JVI.02607-09
PG 11
WC Virology
SC Virology
GA 597CQ
UT WOS:000277733900006
PM 20375158
ER
PT J
AU Pagan, I
Holmes, EC
AF Pagan, Israel
Holmes, Edward C.
TI Long-Term Evolution of the Luteoviridae: Time Scale and Mode of Virus
Speciation
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID POTATO-LEAFROLL-VIRUS; YELLOW DWARF VIRUS; OVERLAPPING READING FRAMES;
RNA VIRUSES; READTHROUGH DOMAIN; MOLECULAR CHARACTERIZATION;
IMMUNODEFICIENCY-VIRUS; SILENCING SUPPRESSOR; POPULATION-GENETICS;
NUCLEOTIDE-SEQUENCE
AB Despite their importance as agents of emerging disease, the time scale and evolutionary processes that shape the appearance of new viral species are largely unknown. To address these issues, we analyzed intra-and interspecific evolutionary processes in the Luteoviridae family of plant RNA viruses. Using the coat protein gene of 12 members of the family, we determined their phylogenetic relationships, rates of nucleotide substitution, times to common ancestry, and patterns of speciation. An associated multigene analysis enabled us to infer the nature of selection pressures and the genomic distribution of recombination events. Although rates of evolutionary change and selection pressures varied among genes and species and were lower in some overlapping gene regions, all fell within the range of those seen in animal RNA viruses. Recombination breakpoints were commonly observed at gene boundaries but less so within genes. Our molecular clock analysis suggested that the origin of the currently circulating Luteoviridae species occurred within the last 4 millennia, with intraspecific genetic diversity arising within the last few hundred years. Speciation within the Luteoviridae may therefore be associated with the expansion of agricultural systems. Finally, our phylogenetic analysis suggested that viral speciation events tended to occur within the same plant host species and country of origin, as expected if speciation is largely sympatric, rather than allopatric, in nature.
C1 [Pagan, Israel; Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Pagan, I (reprint author), Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
EM jip3@psu.edu
RI Pagan, Israel/H-1843-2015;
OI Pagan, Israel/0000-0001-8876-1194; Holmes, Edward/0000-0001-9596-3552
FU Marie Curie [PIOF-GA-2009-236470]; NIH [R01 GM080533]
FX This work was supported by Marie Curie fellowship PIOF-GA-2009-236470 to
I.P. and NIH grant R01 GM080533 awarded to E.C.H.
NR 75
TC 46
Z9 48
U1 0
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD JUN
PY 2010
VL 84
IS 12
BP 6177
EP 6187
DI 10.1128/JVI.02160-09
PG 11
WC Virology
SC Virology
GA 597CQ
UT WOS:000277733900030
PM 20375155
ER
PT J
AU Bar, KJ
Li, H
Chamberland, A
Tremblay, C
Routy, JP
Grayson, T
Sun, CX
Wang, SY
Learn, GH
Morgan, CJ
Schumacher, JE
Haynes, BF
Keele, BF
Hahn, BH
Shaw, GM
AF Bar, Katharine J.
Li, Hui
Chamberland, Annie
Tremblay, Cecile
Routy, Jean Pierre
Grayson, Truman
Sun, Chuanxi
Wang, Shuyi
Learn, Gerald H.
Morgan, Charity J.
Schumacher, Joseph E.
Haynes, Barton F.
Keele, Brandon F.
Hahn, Beatrice H.
Shaw, George M.
TI Wide Variation in the Multiplicity of HIV-1 Infection among Injection
Drug Users
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; COCAINE CO-USE; SELECTIVE TRANSMISSION;
RHESUS MACAQUES; MONTREAL; DIVERSITY; VARIANTS; VACCINE; TRIAL; RISK
AB Recent studies indicate that sexual transmission of human immunodeficiency virus type 1 (HIV-1) generally results from productive infection by only one virus, a finding attributable to the mucosal barrier. Surprisingly, a recent study of injection drug users (IDUs) from St. Petersburg, Russia, also found most subjects to be acutely infected by a single virus. Here, we show by single-genome amplification and sequencing in a different IDU cohort that 60% of IDU subjects were infected by more than one virus, including one subject who was acutely infected by at least 16 viruses. Multivariant transmission was more common in IDUs than in heterosexuals (60% versus 19%; odds ratio, 6.14; 95% confidence interval [CI], 1.37 to 31.27; P = 0.008). These findings highlight the diversity in HIV-1 infection risks among different IDU cohorts and the challenges faced by vaccines in protecting against this mode of infection.
C1 [Bar, Katharine J.; Li, Hui; Grayson, Truman; Sun, Chuanxi; Wang, Shuyi; Learn, Gerald H.; Morgan, Charity J.; Schumacher, Joseph E.; Hahn, Beatrice H.; Shaw, George M.] Univ Alabama, Birmingham, AL 35294 USA.
[Chamberland, Annie] CHUM, Ctr Rech, Montreal, PQ, Canada.
[Tremblay, Cecile] Univ Montreal, Montreal, PQ, Canada.
[Routy, Jean Pierre] McGill Univ, Ctr Hlth, Immunodeficiency Serv, Montreal, PQ, Canada.
[Routy, Jean Pierre] McGill Univ, Ctr Hlth, Div Hematol, Montreal, PQ, Canada.
[Haynes, Barton F.] Duke Univ, Med Ctr, Durham, NC 27710 USA.
[Keele, Brandon F.] NCI, SAIC Frederick, Frederick, MD 21701 USA.
RP Shaw, GM (reprint author), Univ Alabama, 720 S 20th St,816 KAUL Bldg, Birmingham, AL 35294 USA.
EM gshaw@uab.edu
FU Center for HIV/AIDS Vaccine Immunology (CHAVI); Canadian Institutes of
Health Research; Fonds de la Recherche en Sante du Quebec; National
Institutes of Health [AI67854, AI27767, HHSN266200400088C]; Bill &
Melinda Gates Foundation [37874]
FX This work was supported by the Center for HIV/AIDS Vaccine Immunology
(CHAVI), the Canadian Institutes of Health Research, Fonds de la
Recherche en Sante du Quebec, and by grants and contracts from the
National Institutes of Health (AI67854, AI27767, and HHSN266200400088C)
and the Bill & Melinda Gates Foundation (grant 37874).
NR 48
TC 96
Z9 98
U1 0
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD JUN
PY 2010
VL 84
IS 12
BP 6241
EP 6247
DI 10.1128/JVI.00077-10
PG 7
WC Virology
SC Virology
GA 597CQ
UT WOS:000277733900037
PM 20375173
ER
PT J
AU Sierra, F
AF Sierra, Felipe
TI Rapamycin Joins the Aging Fray
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Editorial Material
ID LIFE-SPAN; RESVERATROL; DISEASE; MICE
C1 NIA, Div Aging Biol, NIH, Bethesda, MD 20892 USA.
RP Sierra, F (reprint author), NIA, Div Aging Biol, NIH, Bethesda, MD 20892 USA.
EM Sierraf@nia.nih.gov
NR 9
TC 6
Z9 6
U1 0
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD JUN
PY 2010
VL 65
IS 6
BP 577
EP 579
DI 10.1093/gerona/glq049
PG 3
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 597CN
UT WOS:000277733600001
PM 20410142
ER
PT J
AU Rosano, C
Venkatraman, VK
Guralnik, J
Newman, AB
Glynn, NW
Launer, L
Taylor, CA
Williamson, J
Studenski, S
Pahor, M
Aizenstein, H
AF Rosano, Caterina
Venkatraman, Vijay K.
Guralnik, Jack
Newman, Anne B.
Glynn, Nancy W.
Launer, Lenore
Taylor, Christopher A.
Williamson, Jeff
Studenski, Stephanie
Pahor, Marco
Aizenstein, Howard
TI Psychomotor Speed and Functional Brain MRI 2 Years After Completing a
Physical Activity Treatment
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Physical activity; Sedentary; fMRI; Executive control function; Older
adults
ID LIFE-STYLE INTERVENTIONS; OLDER-ADULTS; CORTICAL PLASTICITY; COGNITIVE
FUNCTION; AGING HUMANS; SEGMENTATION; INDEPENDENCE; EXERCISE; FITNESS;
FMRI
AB Short-term adherence to physical activity (PA) in older adults improves psychomotor processing abilities and is associated with greater brain activation. It is not known whether these associations are also significant for longer-term adherence to moderate-intensity activities.
We measured the cross-sectional association of regular walking with brain activation while performing the digit symbol substitution test (DSST). Participants of the lifestyle interventions and independence for elders-pilot study were examined 2 years after completing a 1-year treatment, consisting of either PA or education in successful aging (SA). Data were obtained from 20 PA participants who reported having remained active for 2 years after the end of the treatment and from 10 SA participants who reported having remained sedentary during the same period (mean age: 81.5 and 80.8 years). Complete brain activation and behavioral data were available for 17 PA and 10 SA participants.
Two years after the formal intervention had ended, the PA group engaged in more minutes of moderate activity and had significantly greater DSST score and higher brain activation within regions important for processing speed (left dorsolateral prefrontal, posterior parietal, and anterior cingulate cortices). Associations were independent of self-reported health, blood pressure, cognition, medication records, gray matter atrophy, and white matter hyperintensities.
Persistent engagement in PA may have beneficial effects on psychomotor processing speed and brain activation, even for moderate levels and even when started late in life. Future studies are warranted to assess whether these beneficial effects are explained by delayed neuronal degeneration and/or new neurogenesis.
C1 [Rosano, Caterina; Newman, Anne B.; Glynn, Nancy W.; Taylor, Christopher A.] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA.
[Venkatraman, Vijay K.; Aizenstein, Howard] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15213 USA.
[Guralnik, Jack; Launer, Lenore] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA.
[Williamson, Jeff] Wake Forest Univ, Dept Internal Med, Sect Gerontol & Geriatr Med, Winston Salem, NC 27109 USA.
[Studenski, Stephanie] Univ Pittsburgh, Dept Med, Div Geriatr Med, Pittsburgh, PA 15213 USA.
[Pahor, Marco] Univ Florida, Dept Aging & Geriatr Res, Inst Aging, Gainesville, FL USA.
[Aizenstein, Howard] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA.
RP Rosano, C (reprint author), Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, 130 N Bellefield St,Room 512, Pittsburgh, PA 15213 USA.
EM rosanoc@edc.pitt.edu
RI Newman, Anne/C-6408-2013; Taylor, Christopher/D-2067-2013;
OI Newman, Anne/0000-0002-0106-1150; Taylor,
Christopher/0000-0002-0937-5461; Glynn, Nancy/0000-0003-2265-0162;
Rosano, Caterina/0000-0002-0909-1506; Rosano,
Caterina/0000-0002-4271-6010
FU National Institute on Aging, National Institutes of Health; Pepper
Scholar [1P30 AGO24827-01]; Beeson Scholar [K23AG028966-01]; National
Institute on Aging [RO3 AG025076-02, R01 AG029232]
FX This work was supported in part by the Intramural Research program and
the National Institute on Aging, National Institutes of Health. Dr.
Rosano is a Pepper Scholar (1P30 AGO24827-01) and Beeson Scholar
(K23AG028966-01) and is supported by the National Institute on Aging
(grant numbers RO3 AG025076-02 and R01 AG029232).
NR 30
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U1 1
U2 28
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD JUN
PY 2010
VL 65
IS 6
BP 639
EP 647
DI 10.1093/gerona/glq038
PG 9
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 597CN
UT WOS:000277733600008
PM 20348185
ER
PT J
AU Stenholm, S
Kronholm, E
Sainio, P
Borodulin, K
Era, P
Fogelholm, M
Partonen, T
Porkka-Heiskanen, T
Koskinen, S
AF Stenholm, Sari
Kronholm, Erkki
Sainio, Paivi
Borodulin, Katja
Era, Pertti
Fogelholm, Mikael
Partonen, Timo
Porkka-Heiskanen, Tarja
Koskinen, Seppo
TI Sleep-Related Factors and Mobility in Older Men and Women
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE General population; Mobility; Older adults; Sleep; Walking
ID LARGE US SAMPLE; INSULIN-RESISTANCE; MUSCLE STRENGTH; RISK-FACTOR;
SUBSEQUENT DISABILITY; WALKING LIMITATIONS; ELDERLY PERSONS; ADULTS;
MORTALITY; PERFORMANCE
AB To examine the association between sleep-related factors and measured and self-reported mobility in a representative sample of older adults.
This study included 2,825 men and women aged 55 years and older participating in a cross-sectional representative population-based Health 2000 Survey in Finland. Sleep duration, insomnia-related symptoms, and fatigue were inquired. Maximal walking speed was measured, and mobility limitation was defined as self-reported difficulties in walking 500 m or stair climbing.
Insomnia-related symptoms and fatigue were prevalent among persons aged 65 years and older in particular. After adjusting for lifestyle factors and diseases, longer sleep (>= 9 hours) was associated with a decreased walking speed in women aged 65 or more years (p = .04) and shorter sleep (< 6 hours) with a higher odds for mobility limitation in women aged 65 or more years (odds ratio [OR] = 1.68, 95% confidence interval [CI] = 1.02-2.75) and in men aged 55-64 years (OR = 3.62, 95% CI = 1.40-9.37) compared with those having a mid-range sleep duration. Sleeping disorders or insomnia was independently associated with both decreased walking speed and mobility limitation in men aged 55 or more years but only with mobility limitation in women aged 65 or more years. Of the sleep-related daytime consequences, "weakness or tiredness" was associated with a decreased walking speed and a higher odds for mobility limitation both in men and in women aged 55 or more years.
Several sleep-related factors, such as sleep duration, insomnia-related symptoms, and fatigue, are associated with measured and self-reported mobility outcomes.
C1 [Stenholm, Sari; Sainio, Paivi; Borodulin, Katja; Koskinen, Seppo] Natl Inst Hlth & Welf, Dept Hlth Funct Capac & Welf, Funct Capac Unit, FI-20720 Turku, Finland.
[Stenholm, Sari] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Kronholm, Erkki] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, FI-20720 Turku, Finland.
[Era, Pertti] Univ Jyvaskyla, Dept Hlth Sci, SF-40351 Jyvaskyla, Finland.
[Fogelholm, Mikael] Acad Finland, Hlth Res Unit, Helsinki, Finland.
[Partonen, Timo] Natl Inst Hlth & Welf, Dept Mental Hlth & Subst Abuse Serv, Helsinki, Finland.
[Porkka-Heiskanen, Tarja] Univ Helsinki, Inst Biomed, FIN-00014 Helsinki, Finland.
RP Stenholm, S (reprint author), Natl Inst Hlth & Welf, Dept Hlth Funct Capac & Welf, Funct Capac Unit, Peltolantie 3, FI-20720 Turku, Finland.
EM sari.stenholm@thl.fi
RI Stenholm, Sari/G-6940-2011; Partonen, Timo/G-1105-2012;
OI Partonen, Timo/0000-0003-1951-2455; Fogelholm,
Mikael/0000-0001-8110-102X; Stenberg, Tarja/0000-0003-1843-7625
FU Finnish Academy [125494 SS]; National Institutes of Health, National
Institute on Aging
FX This study was supported by grant from the Finnish Academy (125494 SS)
and in part by the Intramural Research Program of the National
Institutes of Health, National Institute on Aging.
NR 39
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Z9 33
U1 0
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD JUN
PY 2010
VL 65
IS 6
BP 649
EP 657
DI 10.1093/gerona/glq017
PG 9
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 597CN
UT WOS:000277733600010
PM 20159778
ER
PT J
AU Klein, WMP
Cerully, JL
Monin, MM
Moore, DA
AF Klein, William M. P.
Cerully, Jennifer L.
Monin, Matthew M.
Moore, Don A.
TI Ability, chance, and ambiguity aversion: Revisiting the competence
hypothesis
SO JUDGMENT AND DECISION MAKING
LA English
DT Article
DE ambiguity; control; competence; choice
ID COMPARATIVE IGNORANCE; DECISION-MAKING; UNCERTAINTY; OVERCONFIDENCE;
PREFERENCE; RISK
AB Individuals are often ambiguity-averse when choosing among purely chance-based prospects (Ellsberg, 1961). However, they often prefer apparently ambiguous ability-based prospects to unambiguous chance-based prospects. According to the competence hypothesis (Heath & Tversky, 1991), this pattern derives from favorable perceptions of one's competence. In most past tests of the competence hypothesis, ambiguity is confounded with personal controllability and the source of the ambiguity (e.g., chance vs. missing information). We unconfound these factors in three experiments and find strong evidence for independent effects of both ambiguity aversion and competence. In Experiment 1, participants preferred an unambiguous chance-based option to an ambiguous ability-based option when the ambiguity derived from chance rather than uncertainty about one's own ability. In Experiments 2 and 3, which used different operationalizations of ambiguity in choice contexts with actual consequences, participants attempted to avoid both ambiguity and chance insofar as they could. These findings support and extend the competence hypothesis by demonstrating ambiguity aversion independent of personal controllability and source of ambiguity.
C1 [Klein, William M. P.; Cerully, Jennifer L.; Monin, Matthew M.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA.
[Moore, Don A.] Carnegie Mellon Univ, Tepper Sch Business, Pittsburgh, PA 15213 USA.
RP Klein, WMP (reprint author), NCI, Behav Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN Room 4060, Bethesda, MD 20892 USA.
EM kleinwm@mail.nih.gov
NR 23
TC 4
Z9 4
U1 2
U2 6
PU SOC JUDGMENT & DECISION MAKING
PI TALLAHASSEE
PA FLORIDA STATE UNIV, TALLAHASSEE, FL 32306-1110 USA
SN 1930-2975
J9 JUDGM DECIS MAK
JI Judgm. Decis. Mak.
PD JUN
PY 2010
VL 5
IS 3
BP 192
EP 199
PG 8
WC Psychology, Multidisciplinary
SC Psychology
GA 616ZP
UT WOS:000279250800007
ER
PT J
AU Lev, O
Miller, FG
Emanuel, EJ
AF Lev, Ori
Miller, Franklin G.
Emanuel, Ezekiel J.
TI The Ethics of Research on Enhancement Interventions
SO KENNEDY INSTITUTE OF ETHICS JOURNAL
LA English
DT Article
ID PRUDENTIAL CONCERN; EXTENDED LIVES; IDENTITY; NEED
AB Biomedical enhancement interventions to make people stronger, smarter, and happier are currently being developed. Research to assess these enhancements should be conducted before their introduction into clinical practice. But, many worry that enhancement research is unethical. Some contend that the practice of biomedical enhancements is unethical; accordingly, research that enables such practice would be unethical. Others suggest that research on enhancement interventions does not promote health, exposing research participants to risks with no potential compensating health benefits either to themselves or to society. Categorically condemning research on biomedical enhancements as unethical is unwarranted, however, since at least some research on biomedical enhancements is likely to produce significant health benefits. Indeed, under certain circumstances enhancement research would be urgent, as it would address major public health concerns. Therefore, a blanket prohibition on enhancement research is unjustified. Instead, like any other clinical research, each proposed enhancement study should be reviewed individually to assess whether it fulfills the ethical requirements that make a clinical study permissible.
C1 [Lev, Ori] NHGRI, Dept Bioeth, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA.
[Miller, Franklin G.] NIMH, Bethesda, MD 20892 USA.
[Miller, Franklin G.] Georgetown Univ, Kennedy Inst Eth, Washington, DC 20057 USA.
[Lev, Ori] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
RP Lev, O (reprint author), NHGRI, Dept Bioeth, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA.
NR 21
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 1054-6863
J9 KENNEDY INST ETHIC J
JI Kennedy Inst. Ethics J.
PD JUN
PY 2010
VL 20
IS 2
SI SI
BP 101
EP 113
PG 13
WC Ethics; Philosophy; Social Issues
SC Social Sciences - Other Topics; Philosophy; Social Issues
GA 612VP
UT WOS:000278933500002
PM 20653248
ER
PT J
AU Veron, D
Reidy, KJ
Bertuccio, C
Teichman, J
Villegas, G
Jimenez, J
Shen, W
Kopp, JB
Thomas, DB
Tufro, A
AF Veron, Delma
Reidy, Kimberly J.
Bertuccio, Claudia
Teichman, Jason
Villegas, Guillermo
Jimenez, Juan
Shen, Wa
Kopp, Jeffrey B.
Thomas, David B.
Tufro, Alda
TI Overexpression of VEGF-A in podocytes of adult mice causes glomerular
disease
SO KIDNEY INTERNATIONAL
LA English
DT Article
DE diabetic glomerulopathy; nephrin; podocyte; proteinuria; VEGF
ID ENDOTHELIAL GROWTH-FACTOR; NITRIC-OXIDE SYNTHASE; DIABETIC-NEPHROPATHY;
GENE-EXPRESSION; NEPHRIN; PHOSPHORYLATION; ANGIOGENESIS; DYSFUNCTION;
INHIBITION; IMPAIRMENT
AB We sought to examine the pathogenic role of excessive VEGF-A expression in podocytes, since it has been reported that diabetic nephropathy and other glomerular diseases are associated with increased VEGF-A expression. The induction of podocyte-specific VEGF164 overexpression in adult transgenic mice led to proteinuria, glomerulomegaly, glomerular basement membrane thickening, mesangial expansion, loss of slit diaphragms, and podocyte effacement. When doxycycline-mediated VEGF164 was stopped, these abnormalities reversed. These findings were associated with reversible downregulation of metalloproteinase 9 and nephrin expression. Using transmission electron microscopy, we established that VEGF-A receptor-2 (VEGFR2) was expressed in podocytes and glomerular endothelial cells. We also found that VEGF164 induced VEGFR2 phosphorylation in podocytes. Further, we were able to co-immunoprecipitate VEGFR2 and nephrin using whole kidney lysates, confirming interaction in vivo. This implies that autocrine and paracrine VEGF-A signaling through VEGFR2 occurs in podocytes and may mediate the glomerular phenotype caused by VEGF164 overexpression. Thus, we suggest that podocyte VEGF164 overexpression in adult mice is sufficient to induce glomerular filtration barrier structural and functional abnormalities similar to those present in murine diabetic nephropathy. Kidney International (2010) 77, 989-999; doi:10.1038/ki.2010.64; published online 10 March 2010
C1 [Veron, Delma; Bertuccio, Claudia; Tufro, Alda] Yale Univ, Dept Pediat, Sch Med, New Haven, CT 06520 USA.
[Reidy, Kimberly J.; Teichman, Jason; Villegas, Guillermo; Shen, Wa] Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA.
[Jimenez, Juan] Albert Einstein Coll Med, Analyt Imaging Facil, Bronx, NY 10467 USA.
[Kopp, Jeffrey B.] NIDDK, Kidney Dis Sect, NIH, Bethesda, MD USA.
[Thomas, David B.] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA.
RP Tufro, A (reprint author), Yale Univ, Dept Pediat, Sch Med, 333 Cedar St,POB 208064, New Haven, CT 06520 USA.
EM alda.tufro@yale.edu
OI Kopp, Jeffrey/0000-0001-9052-186X
FU NIH [RO1 DK59333, T32 DK 007110]; O'Brien Center [P50 DK64236]; NIDDK
FX We thank A. Akeson and J. Whittsett (Cincinnati Children's Hospital) for
providing the tet-O-VEGF164 mice. We thank Lawrence Holzman
for providing nephrin antibodies and thoughtful advice. We thank Frank
Macaluso and Leslie Cummings (AECOM Imaging Facility) for technical
assistance with TEM. Portions of this work were presented at the 2007
ASN meeting. This study was supported by the NIH RO1 DK59333 and O'Brien
Center Grant P50 DK64236 (to AT). KJR was supported by the NIH training
Grant T32 DK 007110. NIDDK intramural research program (to JBK).
NR 41
TC 71
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U1 0
U2 5
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 JUN
PY 2010
VL 77
IS 11
BP 989
EP 999
DI 10.1038/ki.2010.64
PG 11
WC Urology & Nephrology
SC Urology & Nephrology
GA 595QG
UT WOS:000277626700008
PM 20375978
ER
PT J
AU Fischer, MJ
Kimmel, PL
Greene, T
Gassman, JJ
Wang, XL
Brooks, DH
Charleston, J
Dowie, D
Thornley-Brown, D
Cooper, LA
Bruce, MA
Kusek, JW
Norris, KC
Lash, JP
AF Fischer, Michael J.
Kimmel, Paul L.
Greene, Tom
Gassman, Jennifer J.
Wang, Xuelei
Brooks, Deborah H.
Charleston, Jeanne
Dowie, Donna
Thornley-Brown, Denyse
Cooper, Lisa A.
Bruce, Marino A.
Kusek, John W.
Norris, Keith C.
Lash, James P.
CA AASK Study Grp
TI Sociodemographic factors contribute to the depressive affect among
African Americans with chronic kidney disease
SO KIDNEY INTERNATIONAL
LA English
DT Article
DE AASK (African American Study of Kidney Disease and Hypertension);
chronic kidney disease; clinical epidemiology; depression; quality of
life
ID QUALITY-OF-LIFE; STAGE RENAL-DISEASE; HEMODIALYSIS-PATIENTS; DIALYSIS
PATIENTS; RACIAL DISPARITIES; UNITED-STATES; MORTALITY; DIAGNOSIS;
SYMPTOMS; INVENTORY
AB Depression is common in end-stage renal disease and is associated with poor quality of life and higher mortality; however, little is known about depressive affect in earlier stages of chronic kidney disease. To measure this in a risk group burdened with hypertension and kidney disease, we conducted a cross-sectional analysis of individuals at enrollment in the African American Study of Kidney Disease and Hypertension Cohort Study. Depressive affect was assessed by the Beck Depression Inventory II and quality of life by the Medical Outcomes Study-Short Form and the Satisfaction with Life Scale. Beck Depression scores over 14 were deemed consistent with an increased depressive affect and linear regression analysis was used to identify factors associated with these scores. Among 628 subjects, 166 had scores over 14 but only 34 were prescribed antidepressants. The mean Beck Depression score of 11.0 varied with the estimated glomerular filtration rate (eGFR) from 10.7 (eGFR 50-60) to 16.0 (eGFR stage 5); however, there was no significant independent association between these. Unemployment, low income, and lower quality and satisfaction with life scale scores were independently and significantly associated with a higher Beck Depression score. Thus, our study shows that an increased depressive affect is highly prevalent in African Americans with chronic kidney disease, is infrequently treated with antidepressants, and is associated with poorer quality of life. Sociodemographic factors have especially strong associations with this increased depressive affect. Because this study was conducted in an African-American cohort, its findings may not be generalized to other ethnic groups. Kidney International (2010) 77, 1010-1019; doi:10.1038/ki.2010.38; published online 3 March 2010
C1 [Fischer, Michael J.] Edward Hines Jr VA Hosp, Ctr Management Complex Chron Care, Hines, IL 60141 USA.
[Fischer, Michael J.; Lash, James P.] Jesse Brown VA Med Ctr, Dept Med, Chicago, IL USA.
[Fischer, Michael J.; Lash, James P.] Univ Illinois, Med Ctr, Chicago, IL USA.
[Kimmel, Paul L.; Kusek, John W.] NIDDK, NIH, Bethesda, MD USA.
[Kimmel, Paul L.] George Washington Univ, Dept Med, Washington, DC USA.
[Greene, Tom] Univ Utah, Dept Med, Salt Lake City, UT 84112 USA.
[Gassman, Jennifer J.; Wang, Xuelei] Cleveland Clin Fdn, Dept Biostat & Epidemiol, Cleveland, OH 44195 USA.
[Brooks, Deborah H.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA.
[Charleston, Jeanne; Cooper, Lisa A.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Dowie, Donna] Columbia Univ, Dept Med, Med Ctr, Harlem Hosp, New York, NY USA.
[Thornley-Brown, Denyse] Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
[Bruce, Marino A.] Meharry Med Coll, Dept Family & Community Med, Nashville, TN 37208 USA.
[Norris, Keith C.] Charles R Drew Univ Med & Sci, Dept Med, Los Angeles, CA 90059 USA.
RP Fischer, MJ (reprint author), Hines VA Hosp, Ctr Management Complex Chron Care, 5000 S 5th Ave 151H, Hines, IL 60141 USA.
EM fischerm@uic.edu
FU National Institutes of Diabetes and Digestive and Kidney Diseases
[5U01DK045388]; National Center for Minority Health and Health
Disparities at the National Institutes of Health [5M01RR00071]; King
Pharmaceuticals; Pfizer; Astra Zeneca Pharmaceuticals; National
Institutes of Health [M01 RR-00080, RR-00071, M01 RR-00827, M01
RR-00032, P20 RR-11145, 2P20 RR-11104, M01 RR-00052, RR-00095,
DK-2818-02]; Department of Veterans Affairs; Veterans Health
Administration, Health Services Research and Development Service (VA
HSRD)
FX Part of these results was presented in abstract and poster format at the
American Society of Nephrology Annual Meeting in November 2008
(Philadelphia, Pennsylvania, USA). A special acknowledgement is extended
to the AASK participants for their time and extraordinary commitment to
the AASK trial and now the AASK cohort study. We also acknowledge all
members of the AASK Collaborative Research Group, which includes
investigators and staff from 21 clinical centers. This study was
supported by cooperative agreements from the National Institutes of
Diabetes and Digestive and Kidney Diseases 5U01DK045388) and the
National Center for Minority Health and Health Disparities at the
National Institutes of Health (5M01RR00071). Support was also provided
by King Pharmaceuticals, Pfizer, and Astra Zeneca Pharmaceuticals. The
following National Institutes of Health institutional grants provided
additional support: M01 RR-00080, RR-00071, M01 RR-00827, M01 RR-00032,
P20 RR-11145, 2P20 RR-11104, M01 RR-00052, RR-00095, and DK-2818-02.
Support was also provided by the Department of Veterans Affairs,
Veterans Health Administration, Health Services Research and Development
Service (VA HSR&D Career Development Award to MJF).
NR 50
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U1 1
U2 7
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 JUN
PY 2010
VL 77
IS 11
BP 1010
EP 1019
DI 10.1038/ki.2010.38
PG 10
WC Urology & Nephrology
SC Urology & Nephrology
GA 595QG
UT WOS:000277626700010
PM 20200503
ER
PT J
AU Groll, A
Seibel, NL
Walsh, TJ
Arnold, L
Arrieta, A
AF Groll, A.
Seibel, N. L.
Walsh, T. J.
Arnold, L.
Arrieta, A.
TI Micafungin - Overview of Efficacy in Pediatric Patients
SO KLINISCHE PADIATRIE
LA English
DT Meeting Abstract
C1 [Groll, A.] Westf Wilhelms Univ Kinderklin, Munster, Germany.
[Seibel, N. L.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Walsh, T. J.] NCI, Bethesda, MD 20892 USA.
[Arnold, L.] Astellas Pharma, Deerfield, IL USA.
[Arrieta, A.] Childrens Hosp Orange Cty, Orange, CA 92668 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0300-8630
J9 KLIN PADIATR
JI Klinische Padiatr.
PD JUN
PY 2010
VL 222
SU 1
BP S48
EP S49
PG 2
WC Pediatrics
SC Pediatrics
GA 633RT
UT WOS:000280523000159
ER
PT J
AU Schmidt, A
Casey, R
Schappell, E
Thumar, B
Bartlett, E
Nutt, A
Collins, P
Murphy, B
Karron, R
AF Schmidt, A.
Casey, R.
Schappell, E.
Thumar, B.
Bartlett, E.
Nutt, A.
Collins, P.
Murphy, B.
Karron, R.
TI Clinical evaluation of new recombinant vaccines against the humane
parainfluenza Type 1, 2 and 3 (HPIVI-3).
SO KLINISCHE PADIATRIE
LA German
DT Meeting Abstract
C1 [Schmidt, A.; Bartlett, E.; Nutt, A.; Collins, P.; Murphy, B.] NIAID, LID, Bethesda, MD 20892 USA.
[Casey, R.; Schappell, E.; Thumar, B.; Karron, R.] Johns Hopkins Sch Publ Hlth, CIR, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0300-8630
J9 KLIN PADIATR
JI Klinische Padiatr.
PD JUN
PY 2010
VL 222
SU 1
BP S8
EP S8
PG 1
WC Pediatrics
SC Pediatrics
GA 633RT
UT WOS:000280523000024
ER
PT J
AU Brown, P
Gipson, C
AF Brown, Patricia
Gipson, Chester
TI A word from OLAW and USDA
SO LAB ANIMAL
LA English
DT Editorial Material
C1 [Brown, Patricia] NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA.
[Gipson, Chester] APHIS, USDA, AC, Washington, DC USA.
RP Brown, P (reprint author), NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0093-7355
J9 LAB ANIMAL
JI Lab Anim.
PD JUN
PY 2010
VL 39
IS 6
BP 167
EP 167
PG 1
WC Veterinary Sciences
SC Veterinary Sciences
GA 605XF
UT WOS:000278381000010
PM 20485353
ER
PT J
AU Wu, TH
Tian, J
Cutler, RG
Telljohann, RS
Bernlohr, DA
Mattson, MP
Handa, JT
AF Wu, Tinghuai
Tian, Jane
Cutler, Roy G.
Telljohann, Richard S.
Bernlohr, David A.
Mattson, Mark P.
Handa, James T.
TI Knockdown of FABP5 mRNA decreases cellular cholesterol levels and
results in decreased apoB100 secretion and triglyceride accumulation in
ARPE-19 cells
SO LABORATORY INVESTIGATION
LA English
DT Article
DE apoB; cholesterol; FABP5; RPE; siRNA; triglycerides
ID ACID-BINDING PROTEIN; LOW-DENSITY-LIPOPROTEIN; INHERITED RETINAL
DYSTROPHY; PIGMENT EPITHELIAL-CELLS; FATTY-ACID; KNOCKOUT MICE; HEPG2
CELLS; RAT-LIVER; RCS RAT; GENE
AB To maintain normal retinal function, retinal pigment epithelial (RPE) cells engulf photoreceptor outer segments (ROS) enriched in free fatty acids (FFAs). We have previously demonstrated fatty acid-binding protein 5 (FABP5) downregulation in the RPE/choroidal complex in a mouse model of aging and early age-related macular degeneration. FABPs are involved in intracellular transport of FFAs and their targeting to specific metabolic pathways. To elucidate the role of FABP5 in lipid metabolism, the production of the FABP5 protein in a human RPE cell line was inhibited using RNA interference technology. As a result, the levels of cholesterol and cholesterol ester were decreased by about 40%, whereas FFAs and triglycerides were increased by 18 and 67% after siRNA treatment, respectively. Some species of phospholipids were decreased in siRNA-treated cells. Cellular lipid droplets were evident and apoB secretion was decreased by 76% in these cells. Additionally, we discovered that ARPE-19 cells could synthesize and secrete Apolipoprotein B100 (apoB100), which may serve as a backbone structure for the formation of lipoprotein particles in these cells. Our results indicate that FABP5 mRNA knockdown results in the accumulation of cellular triglycerides, decreased cholesterol levels, and reduced secretion of apoB100 protein and lipoprotein-like particles. These observations indicated that FABP5 plays a critical role in lipid metabolism in RPE cells, suggesting that FABP5 downregulation in the RPE/choroid complex in vivo might contribute to aging and early age-related macular degeneration. Laboratory Investigation (2010) 90, 906-914; doi:10.1038/labinvest.2009.33; published online 11 May 2009
C1 [Wu, Tinghuai; Tian, Jane; Handa, James T.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
[Cutler, Roy G.; Telljohann, Richard S.; Mattson, Mark P.] Natl Inst Aging Intramural Res Program, Neurosci Lab, Baltimore, MD USA.
[Bernlohr, David A.] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN USA.
RP Wu, TH (reprint author), Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
EM tingwu@jhmi.edu
RI Mattson, Mark/F-6038-2012
FU NEI EY [14005]; AHAF Macular Degeneration Grant; Research to Prevent
Blindness Clinician Scientist award; RPB grant; National Insitute on
Aging [DK053189]
FX This work was supported by NEI EY 14005 (JTH), an AHAF Macular
Degeneration Grant (JTH), a Research to Prevent Blindness Clinician
Scientist award (JTH), an unrestricted RPB grant, the Intramural
Research Program of the National Insitute on Aging, DK053189 (DAB), and
gifts from Ric and Sandy Forsythe, The Kwok family the Merlau family,
and Aleda Wright.
NR 46
TC 2
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U1 2
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD JUN
PY 2010
VL 90
IS 6
BP 906
EP 914
DI 10.1038/labinvest.2009.33
PG 9
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 601UV
UT WOS:000278091300009
PM 19434059
ER
PT J
AU Cappuzzo, F
Ciuleanu, T
Stelmakh, L
Cicenas, S
Szczesna, A
Juhasz, E
Esteban, E
Molinier, O
Brugger, W
Melezinek, I
Klingelschmitt, G
Klughammer, B
Giaccone, G
AF Cappuzzo, Federico
Ciuleanu, Tudor
Stelmakh, Lilia
Cicenas, Saulius
Szczesna, Aleksandra
Juhasz, Erzsebet
Esteban, Emilio
Molinier, Olivier
Brugger, Wolfram
Melezinek, Ivan
Klingelschmitt, Gaelle
Klughammer, Barbara
Giaccone, Giuseppe
TI Erlotinib as maintenance treatment in advanced non-small-cell lung
cancer: a multicentre, randomised, placebo-controlled phase 3 study
SO LANCET ONCOLOGY
LA English
DT Article
ID CISPLATIN PLUS GEMCITABINE; III TRIAL; CHEMOTHERAPY; THERAPY;
CARBOPLATIN; PACLITAXEL; BEVACIZUMAB; COMBINATION; INSTITUTE; DURATION
AB Background First-line chemotherapy for advanced non-small-cell lung cancer (NSCLC) is usually limited to four to six cycles. Maintenance therapy can delay progression and prolong survival. The oral epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor erlotinib has proven efficacy and tolerability in second-line NSCLC. We designed the phase 3, placebo-controlled Sequential Tarceva in Unresectable NSCLC (SATURN; BO18192) study to assess use of erlotinib as maintenance therapy in patients with non-progressive disease following first-line platinum-doublet chemotherapy.
Methods Between December, 2005, and May, 2008, 1949 patients were included in the run-in phase (four cycles of platinum-based chemotherapy). At the end of the run-in phase, 889 patients who did not have progressive disease were entered into the main study, and were randomly allocated using a 1:1 adaptive randomisation method through a third-party interactive voice response system to receive erlotinib (150 mg/day; n=438) or placebo (n=451) until progression or unacceptable toxicity. Patients were stratified by EGFR immunohistochemistry status, stage, Eastern Cooperative Oncology Group performance status, chemotherapy regimen, smoking history, and region. Co-primary endpoints were progression-free survival (PFS) in all analysable patients irrespective of EGFR status, and PFS in patients whose tumours had EGFR protein overexpression, as determined by immunohistochemistry. This study is registered with www.ClinicalTrials.gov, number NCT00556712.
Findings 884 patients were analysable for PFS; 437 in the erlotinib group and 447 in the placebo group. After a median follow-up of 11.4 months for the erlotinib group and 11.5 months for the placebo group, median PFS was significantly longer with erlotinib than with placebo: 12.3 weeks for patients in the erlotinib group versus 11.1 weeks for those in the placebo group (HR 0.71, 95% CI 0.62-0.82; p<0.0001). PFS was also significantly longer in patients with EGFR-positive immunohistochemistry who were treated with erlotinib (n=307) compared with EGFR-positive patients given placebo (n=311; median PFS 12.3 weeks in the erlotinib group vs 11.1 weeks in the placebo group; HR 0.69, 0.58-0.82; p<0.0001). The most common grade 3 or higher adverse events were rash (37 [9%] of 443 patients in the erlotinib group vs none of 445 in the placebo group) and diarrhoea (seven [2%] of 443 patients vs none of 445). Serious adverse events were reported in 47 patients (11%) on erlotinib compared with 34 patients (8%) on placebo. The most common serious adverse event was pneumonia (seven cases [2%1 with erlotinib and four [<1%] with placebo).
Interpretation Maintenance therapy with erlotinib for patients with NSCLC is well tolerated and significantly prolongs PFS compared with placebo. First-line maintenance with erlotinib could be considered in patients who do not progress after four cycles of chemotherapy.
C1 [Cappuzzo, Federico] Osped Civile Livorno, Dept Med Oncol, I-57100 Livorno, Italy.
[Ciuleanu, Tudor] Inst Oncol Ion Chiricuta, Cluj Napoca, Romania.
[Stelmakh, Lilia] Pavlov State Med Univ, Lab Thorac Oncol, Res & Sci Inst Pulmonol, St Petersburg, Russia.
[Cicenas, Saulius] Vilnius State Univ, Inst Oncol, Dept Thorac Surg & Oncol, Vilnius, Lithuania.
[Szczesna, Aleksandra] Mazowieckie Cent Leczenia Chorob Pluc & Gruzlicy, Otwock, Poland.
[Juhasz, Erzsebet] Koranyi Natl Inst TB & Pulmonol I & XIV, Budapest, Hungary.
[Esteban, Emilio] Hosp Univ Cent Asturias, Dept Med Oncol, Oviedo, Spain.
[Molinier, Olivier] Ctr Hosp Mans, Dept Resp Dis, Le Mans, France.
[Brugger, Wolfram] Univ Freiburg, Teaching Hosp, Schwarzwald Baar Clin, Dept Hematol Oncol, Villingen Schwenningen, Germany.
[Melezinek, Ivan] Roche Prod Ltd, Clin Sci, Welwyn Garden City AL7 3AY, Herts, England.
[Klingelschmitt, Gaelle; Klughammer, Barbara] F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland.
[Giaccone, Giuseppe] NIH, Med Oncol Branch, Bethesda, MD 20892 USA.
RP Cappuzzo, F (reprint author), Osped Civile Livorno, Dept Med Oncol, Viale Alfieri 36, I-57100 Livorno, Italy.
EM f.cappuzzo@us16.toscana.it
RI Ciuleanu, Tudor Eliade/C-3996-2011; Giaccone, Giuseppe/E-8297-2017;
OI Giaccone, Giuseppe/0000-0002-5023-7562; Cappuzzo,
Federico/0000-0002-6295-6767
FU F Hoffmann-La Roche Ltd; Roche; Eli-Lilly; AstraZeneca; Boehringer;
Pfizer; Amgen; Lilly; Rhiannon Owen of Gardiner-Caldwell Communications
FX - F Hoffmann-La Roche Ltd.; FC has received honoraria from Roche,
Eli-Lilly, AstraZeneca, and Boehringer, and payment for development of
educational presentations including service on speakers' bureaus from
Roche, Eli-Lilly, AstraZeneca, and Boehringer. TC has received payment
for development of educational presentations including service on
speakers' bureaus from Roche, Eli-Lilly, Pfizer, and Amgen. EJ has
received honoraria and travel and accommodation expenses from Roche, and
has patents planned, pending, or issued. WB has received support for
travel to meetings for the study from F Hoffmann-La Roche and his
institution received a supply of the study drug and support with
clinical report form entries. WB has also received payment for local ad
boards and oral presentations at meetings, and honoraria from Roche,
Lilly, and AstraZeneca, and travel and accommodation expenses from Roche
and Lilly. IM and GK are employees of F Hoffmann-La Roche. BK is an
employee of F Hoffmann-La Roche and has stock options with F Hoffmann-La
Roche. LS, SC, AS, EE, OM, and GG have no conflicts to declare.; The
study was sponsored by F Hoffmann-La Roche and medical writing support
was provided by Rhiannon Owen of Gardiner-Caldwell Communications; this
support was funded by F Hoffmann-La Roche. We thank all the patients who
participated in the SATURN study, and their families. The authors would
also like to thank the late Ulrich Brennscheidt (formerly of F
Hoffmann-La Roche) for his work in designing the protocol for the SATURN
study.
NR 27
TC 663
Z9 706
U1 8
U2 65
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
J9 LANCET ONCOL
JI Lancet Oncol.
PD JUN
PY 2010
VL 11
IS 6
BP 521
EP 529
DI 10.1016/S1470-2045(10)70112-1
PG 9
WC Oncology
SC Oncology
GA 613YA
UT WOS:000279019500024
PM 20493771
ER
PT J
AU Kobayashi, H
Longmire, MR
Ogawa, M
Choyke, PL
Kawamoto, S
AF Kobayashi, Hisataka
Longmire, Michelle R.
Ogawa, Mikako
Choyke, Peter L.
Kawamoto, Satomi
TI Multiplexed imaging in cancer diagnosis: applications and future
advances
SO LANCET ONCOLOGY
LA English
DT Review
ID CELL LUNG-CANCER; DUAL-ENERGY CT; LABELED MONOCLONAL-ANTIBODIES; ACUTE
MYOCARDIAL-INFARCTION; INTEGRATED FDG PET/CT; WHOLE-BODY MRI; IN-VIVO;
ATTENUATION CORRECTION; MAGNETIC-RESONANCE; EMISSION-TOMOGRAPHY
AB The development of imaging technologies that have sufficient specificity and sensitivity to enable early, accurate detection of cancer and response to therapy has long been a goal in oncology. Various radiological techniques have been used for diagnosis and surveillance of disease recurrence and imaging has revolutionised oncology. However, despite the widespread use of technologies, the ability of currently available imaging methods to facilitate early detection, precise characterisation, and accurate localisation of maligant disease could be improved. The simultaneous use of two or more techniques, contrast reagents, signalling methods, or the coupling of agent and tissue properties to achieve so-called multiplexed imaging is a promising approach. In this review, we provide a broad overview of current and emerging multiplexed, imaging technologies.
C1 [Kobayashi, Hisataka; Longmire, Michelle R.; Ogawa, Mikako; Choyke, Peter L.] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Kawamoto, Satomi] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA.
RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,Room 1B40,MSC1088, Bethesda, MD 20892 USA.
EM kobayash@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.
NR 63
TC 37
Z9 37
U1 2
U2 15
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
J9 LANCET ONCOL
JI Lancet Oncol.
PD JUN
PY 2010
VL 11
IS 6
BP 589
EP 595
DI 10.1016/S1470-2045(10)70009-7
PG 7
WC Oncology
SC Oncology
GA 613YA
UT WOS:000279019500031
PM 20338808
ER
PT J
AU Kyle, RA
Durie, BGM
Rajkumar, SV
Landgren, O
Blade, J
Merlini, G
Kroger, N
Einsele, H
Vesole, DH
Dimopoulos, M
San Miguel, J
Avet-Loiseau, H
Hajek, R
Chen, WM
Anderson, KC
Ludwig, H
Sonneveld, P
Pavlovsky, S
Palumbo, A
Richardson, PG
Barlogie, B
Greipp, P
Vescio, R
Turesson, I
Westin, J
Boccadoro, M
AF Kyle, R. A.
Durie, B. G. M.
Rajkumar, S. V.
Landgren, O.
Blade, J.
Merlini, G.
Kroeger, N.
Einsele, H.
Vesole, D. H.
Dimopoulos, M.
San Miguel, J.
Avet-Loiseau, H.
Hajek, R.
Chen, W. M.
Anderson, K. C.
Ludwig, H.
Sonneveld, P.
Pavlovsky, S.
Palumbo, A.
Richardson, P. G.
Barlogie, B.
Greipp, P.
Vescio, R.
Turesson, I.
Westin, J.
Boccadoro, M.
CA Int Myeloma Working Grp
TI Monoclonal gammopathy of undetermined significance (MGUS) and smoldering
(asymptomatic) multiple myeloma: IMWG consensus perspectives risk
factors for progression and guidelines for monitoring and management
SO LEUKEMIA
LA English
DT Review
DE monoclonal gammopathy of undetermined significance; smoldering multiple
myeloma; International Myeloma Working Group; MGUS
ID LIGHT-CHAIN RATIO; MALIGNANT-TRANSFORMATION; FLOW-CYTOMETRY;
PLASMA-CELLS; LONG-TERM; PREVALENCE; RECOGNITION; PROGNOSIS; CRITERIA;
BONE
AB Monoclonal gammopathy of undetermined significance (MGUS) was identified in 3.2% of 21 463 residents of Olmsted County, Minnesota, 50 years of age or older. The risk of progression to multiple myeloma, Waldenstrom's macroglobulinemia, AL amyloidosis or a lymphoproliferative disorder is approximately 1% per year. Low-risk MGUS is characterized by having an M protein < 15 g/l, IgG type and a normal free light chain (FLC) ratio. Patients should be followed with serum protein electrophoresis at six months and, if stable, can be followed every 2-3 years or when symptoms suggestive of a plasma cell malignancy arise. Patients with intermediate and high-risk MGUS should be followed in 6 months and then annually for life. The risk of smoldering (asymptomatic) multiple myeloma (SMM) progressing to multiple myeloma or a related disorder is 10% per year for the first 5 years, 3% per year for the next 5 years and 1-2% per year for the next 10 years. Testing should be done 2-3 months after the initial recognition of SMM. If the results are stable, the patient should be followed every 4-6 months for 1 year and, if stable, every 6-12 months. Leukemia (2010) 24, 1121-1127; doi:10.1038/leu.2010.60; published online 22 April 2010
C1 [Kyle, R. A.; Rajkumar, S. V.; Greipp, P.] Mayo Clin, Div Hematol, Rochester, MN 55905 USA.
[Durie, B. G. M.; Vescio, R.] Samuel Oschin Comprehens Canc Inst, Cedars Sinai Outpatient Canc Ctr, Aptium Oncol Inc, Los Angeles, CA USA.
[Landgren, O.] NCI, NIH, Bethesda, MD 20892 USA.
[Blade, J.] Hosp Clin Barcelona, IDIBAPS, Dept Hematol, Barcelona, Spain.
[Merlini, G.] Univ Hosp San Matteo, Dept Biochem, Pavia, Italy.
[Kroeger, N.] Univ Hamburg Hosp, Dept Stem Cell Transplantat, D-2000 Hamburg, Germany.
[Einsele, H.] Univ Wurzburg, Dept Internal Med, Wurzburg, Germany.
[Vesole, D. H.] Hackensack Univ Med Ctr, Hackensack Canc Ctr, Hackensack, NJ USA.
[Dimopoulos, M.] Univ Athens, Sch Med, Dept Therapeut, GR-11527 Athens, Greece.
[San Miguel, J.] Hosp Univ Salamanca, IBMCC USAL CSIC Salamanca, Serv Hematol, Dept Hematol,CIC, Salamanca, Spain.
[Avet-Loiseau, H.] Inst Biol, Hematol Lab, Nantes, France.
[Hajek, R.] Univ Hosp Brno, Dept Internal Med Hematol, Brno, Czech Republic.
[Chen, W. M.] Beijing Chaoyang Hosp, Dept Hematol & Oncol, Beijing, Peoples R China.
[Anderson, K. C.; Richardson, P. G.] Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancies, Boston, MA 02115 USA.
[Ludwig, H.] Wilhelminenspital Stadt Wien, Ctr Oncol & Hematol, Dept Med 1, Vienna, Austria.
[Sonneveld, P.] Erasmus MC, Dept Hematol, Rotterdam, Netherlands.
[Pavlovsky, S.] Angel Ocampo Hosp, FUNDALEU, Buenos Aires, DF, Argentina.
[Palumbo, A.; Boccadoro, M.] Univ Turin, Div Ematol, Turin, Italy.
[Barlogie, B.] MIRT UAMS, Dept Hematol, Little Rock, AR USA.
[Barlogie, B.] MIRT UAMS, Dept Pathol, Little Rock, AR USA.
[Turesson, I.] Malmo Univ Hosp, Dept Hematol, Malmo, Sweden.
[Westin, J.] Sahlgrens Univ Hosp, Dept Hematol, Gottenburg, Sweden.
RP Kyle, RA (reprint author), Mayo Clin, Div Hematol, 200 1st St SW,Stabile 6-28, Rochester, MN 55905 USA.
EM kyle.robert@mayo.edu
RI Waage, Anders/D-7705-2013; FACON, THIERRY/M-9736-2014; Garcia-Sanz,
Ramon/B-7986-2017;
OI FACON, THIERRY/0000-0001-7705-8460; Garcia-Sanz,
Ramon/0000-0003-4120-2787; SAN MIGUEL, JESUS/0000-0002-9183-4857;
Rajkumar, S. Vincent/0000-0002-5862-1833; Merlini,
Giampaolo/0000-0001-7680-3254
NR 23
TC 260
Z9 273
U1 1
U2 30
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD JUN
PY 2010
VL 24
IS 6
BP 1121
EP 1127
DI 10.1038/leu.2010.60
PG 7
WC Oncology; Hematology
SC Oncology; Hematology
GA 608HV
UT WOS:000278575400003
PM 20410922
ER
PT J
AU Zingone, A
Cultraro, CM
Shin, DM
Bean, CM
Morse, HC
Janz, S
Kuehl, WM
AF Zingone, A.
Cultraro, C. M.
Shin, D-M
Bean, C. M.
Morse, H. C., III
Janz, S.
Kuehl, W. M.
TI Ectopic expression of wild-type FGFR3 cooperates with MYC to accelerate
development of B-cell lineage neoplasms
SO LEUKEMIA
LA English
DT Article
DE FGFR3; Myc; lymphoma; multiple myeloma; oncogene
ID GROWTH-FACTOR RECEPTOR-3; MULTIPLE-MYELOMA CELLS; TUMOR PROGRESSION;
GENETIC EVENTS; ACTIVATION; MICE; CLASSIFICATION; APOPTOSIS; ONCOGENE;
TARGET
AB The t(4;14) translocation in multiple myeloma (MM) simultaneously dysregulates two apparent oncogenes: fibroblast growth factor receptor 3 (FGFR3) controlled by the 3' immunoglobulin heavy chain enhancer on der(14) and MMSET controlled by the intronic E mu enhancer on der(4). Although all MM tumors and cell lines with a t(4;14) translocation have dysregulated MMSET, about 25% do not express FGFR3. Therefore, the function of dysregulated wild-type (WT) FGFR3 in the pathogenesis of MM remains unclear. We developed a murine transgenic (TG) model in which WT FGFR3 is overexpressed in B lymphoid cells. Although high levels of FGFR3 resulted in lymphoid hyperplasia in about one-third of older mice, no increase in tumorigenesis was observed. However, double TG FGFR3/Myc mice develop mature B lymphoma tumors that occur with a higher penetrance and shorter latency than in single TG Myc mice (P = 0.006). We conclude that expression of high levels of WT FGFR3 can be oncogenic and cooperate with MYC to generate B lymphoid tumors. This suggests that dysregulated FGFR3 expression is likely to be essential at least for the early stages of pathogenesis of MM tumors that have a t(4;14) translocation. Leukemia (2010) 24, 1171-1178; doi:10.1038/leu.2010.50; published online 15 April 2010
C1 [Zingone, A.; Cultraro, C. M.; Bean, C. M.; Kuehl, W. M.] Bethesda Naval Hosp, Genet Branch, Ctr Canc Res, NCI,NIH, Bethesda, MD 20889 USA.
[Shin, D-M; Morse, H. C., III] NIAID, Immunopathol Lab, NIH, Rockville, MD USA.
[Morse, H. C., III] Univ Iowa, Roy J & Lucille Carver Coll Med, Dept Pathol, Iowa City, IA USA.
RP Kuehl, WM (reprint author), Bethesda Naval Hosp, Genet Branch, Ctr Canc Res, NCI,NIH, Bldg 8,Room 5101, Bethesda, MD 20889 USA.
EM wmk@helix.nih.gov
OI Morse, Herbert/0000-0002-9331-3705
FU NIH; National Cancer Institute [P50CA097274]; Center for Cancer
Research; National Institute of Allergy and Infectious Diseases
FX We thank Marta Chesi (Mayo Clinic, Scottsdale, AZ) for providing
immunohistochemistry (Figures 1c-f). This work was supported in part by
the Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research (WMK), and National Institute of Allergy and
Infectious Diseases (HCM), and Award Number P50CA097274 from the
National Cancer Institute (SJ).
NR 44
TC 10
Z9 10
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD JUN
PY 2010
VL 24
IS 6
BP 1171
EP 1178
DI 10.1038/leu.2010.50
PG 8
WC Oncology; Hematology
SC Oncology; Hematology
GA 608HV
UT WOS:000278575400009
PM 20393505
ER
PT J
AU Hassan, R
Schweizer, C
Lu, KF
Schuler, B
Remaley, AT
Weil, SC
Pastan, I
AF Hassan, Raffit
Schweizer, Charles
Lu, Kun F.
Schuler, Barbara
Remaley, Alan T.
Weil, Susan C.
Pastan, Ira
TI Inhibition of mesothelin-CA-125 interaction in patients with
mesothelioma by the anti-mesothelin monoclonal antibody MORAb-009:
Implications for cancer therapy
SO LUNG CANCER
LA English
DT Article
DE Mesothelioma; Mesothelin; CA-125; MORAb-009; Metastasis; Peritoneal
mesothelioma; Ovarian cancer
ID OVARIAN-CANCER; PERITONEAL MESOTHELIOMA; MOLECULAR-CLONING;
HIGH-AFFINITY; CA-125; CA125; SERUM; DIAGNOSIS; MARKER; ADENOCARCINOMAS
AB Background: Mesothelin, a tumor differentiation antigen highly expressed in mesothelioma and ovarian cancer, is the receptor for CA-125 (MUC 16) and this interaction may play a role in tumor metastasis. MORAb-009 is a chimeric anti-mesothelin monoclonal antibody.
Methods: Twenty-four patients with mesothelin expressing cancers were treated on a phase I study of MORAb-009 administered as an intravenous infusion (12.5-400 mg/m(2)) weekly x 4 doses with 2 weeks off before the next cycle. This report summarizes the effect of MORAb-009 on serum CA-125 kinetics in the eight patients with mesothelioma who had CA-125 levels measured before and at different time-points following therapy.
Results: MORAb-009 treatment led to a marked increase in serum CA-125 levels in all patients including those without elevated CA-125 levels before therapy. The increase in CA-125 levels was not due to disease progression since CA-125 levels decreased rapidly after stopping MORAb-009 therapy. No patients had signs of peritoneal or pleural inflammation as the possible cause of CA-125 rise. In addition, the elevated CA-125 levels were not due to MORAb-009 interfering with the laboratory assay used to measure CA-125.
Conclusion: The increase in serum CA-125 produced by treatment with MORAb-009 is most likely due to MORAb-009 inhibiting the binding of tumor shed CA-125 to mesothelin present on mesothelial cells lining the pleural and peritoneal cavities. Inhibiting the mesothelin CA-125 interaction could be a useful strategy to prevent tumor metastasis in mesotheliomas and ovarian cancer. Published by Elsevier Ireland Ltd.
C1 [Hassan, Raffit; Lu, Kun F.; Schuler, Barbara; Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Schweizer, Charles; Weil, Susan C.] Morphotek Inc, Exton, PA USA.
[Remaley, Alan T.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Hassan, R (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Rm 5116, Bethesda, MD 20892 USA.
EM hassanr@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX Funding: This research was supported by the Intramural Research Program
of the National Institutes of Health, National Cancer Institute, Center
for Cancer Research. The clinical trial was conducted under a Clinical
Research and Development Agreement between the National Cancer Institute
and Morphotek Inc.
NR 29
TC 31
Z9 31
U1 1
U2 5
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0169-5002
J9 LUNG CANCER
JI Lung Cancer
PD JUN
PY 2010
VL 68
IS 3
BP 455
EP 459
DI 10.1016/j.lungcan.2009.07.016
PG 5
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 607DK
UT WOS:000278478700022
PM 19744744
ER
PT J
AU Jain, MS
Danoff, JV
Paul, SM
AF Jain, M. S.
Danoff, J. V.
Paul, S. M.
TI CORRELATION BETWEEN BIOELECTRICAL SPECTROSCOPY AND PEROMETRY IN
ASSESSMENT OF UPPER EXTREMITY SWELLING
SO LYMPHOLOGY
LA English
DT Article
DE bioelectrical spectroscopy; bioimpedance; breast cancer; lymphedema;
volumetry
ID BREAST-CANCER SURVIVORS; BIOIMPEDANCE MEASURES; LYMPHEDEMA TREATMENT;
WATER DISPLACEMENT; EARLY-DIAGNOSIS; FOLLOW-UP; IMPEDANCE; RELIABILITY;
AGREEMENT; VOLUMETRY
AB Lymphedema is a common side effect of breast cancer treatment and is associated with increased upper extremity volume, functional impairment, and pain. While there is no cure for lymphedema, physical therapy treatment can often alleviate symptoms. To measure the efficacy of treatment, accurate assessment of the limbs is important. Current methods of assessment are complex (water displacement), marginally accurate (circumferential measurements), or expensive (opto-electrical systems). A new method for estimating tissue fluid is bioelectrical spectroscopy (BIS). This method measures impedance to small currents applied to the body and is easily performed. Acceptance of BIS devices for assessment of limb fluid will be dependent on the establishment of sufficient reliability and validity, and the objective of this study was to evaluate reliability and validity of this device compared to perometry. Both upper limbs of ten subjects previously treated for breast cancer were measured using BIS and perometry. We found that inter-rater reliability (r=0.987) and intrarater reliability (r=0.993) were acceptably high for the BIS unit and concurrent validity was r=-0.904, when compared to perometry. These results confirm that BIS can produce valid and reliable data related to the assessment of upper limbs affected by lymphedema.
C1 [Jain, M. S.; Paul, S. M.] NIH, Dept Rehabil Med, Mark O Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
[Danoff, J. V.] George Washington Univ, Med Ctr, Dept Exercise Sci, Sch Publ Hlth, Washington, DC 20037 USA.
RP Jain, MS (reprint author), NIH, Dept Rehabil Med, Mark O Hatfield Clin Res Ctr, Bldg 10,CRC 1-1469,10 Ctr Dr,MSC 1604, Bethesda, MD 20892 USA.
EM mina_jain@nih.gov
OI Paul, Scott/0000-0003-1274-6670
NR 28
TC 17
Z9 17
U1 0
U2 5
PU LYMPHOLOGY
PI TUCSON
PA C/O C L WITTE MD 1501 N CAMPBELL AVE DEPT SURGERY, TUCSON, AZ 85724 USA
SN 0024-7766
J9 LYMPHOLOGY
JI Lymphology
PD JUN
PY 2010
VL 43
IS 2
BP 85
EP 94
PG 10
WC Immunology; Physiology
SC Immunology; Physiology
GA 632YJ
UT WOS:000280465500005
PM 20848996
ER
PT J
AU Qian, XN
Tagare, HD
Fulbright, RK
Long, R
Antani, S
AF Qian, Xiaoning
Tagare, Hemant D.
Fulbright, Robert K.
Long, Rodney
Antani, Sameer
TI Optimal embedding for shape indexing in medical image databases
SO MEDICAL IMAGE ANALYSIS
LA English
DT Article
DE Shape-based similarity retrieval; Shape space; Indexing trees; Embedding
ID METRIC-SPACES; RETRIEVAL; CURVES
AB This paper addresses the problem of indexing shapes in medical image databases. Shapes of organs are often indicative of disease, making shape similarity queries important in medical image databases. Mathematically, shapes with landmarks belong to shape spaces which are curved manifolds with a well defined metric. The challenge in shape indexing is to index data in such curved spaces. One natural indexing scheme is to use metric trees, but metric trees are prone to inefficiency. This paper proposes a more efficient alternative.
We show that it is possible to optimally embed finite sets of shapes in shape space into a Euclidean space. After embedding, classical coordinate-based trees can be used for efficient shape retrieval. The embedding proposed in the paper is optimal in the sense that it least distorts the partial Procrustes shape distance.
The proposed indexing technique is used to retrieve images by vertebral shape from the NHANES II database of cervical and lumbar spine X-ray images maintained at the National Library of Medicine. Vertebral shape strongly correlates with the presence of osteophytes, and shape similarity retrieval is proposed as a tool for retrieval by osteophyte presence and severity.
Experimental results included in the paper evaluate (1) the usefulness of shape similarity as a proxy for osteophytes, (2) the computational and disk access efficiency of the new indexing scheme, (3) the relative performance of indexing with embedding to the performance of indexing without embedding, and (4) the computational cost of indexing using the proposed embedding versus the cost of an alternate embedding. The experimental results clearly show the relevance of shape indexing and the advantage of using the proposed embedding. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Qian, Xiaoning; Tagare, Hemant D.] Yale Univ, Dept Elect Engn, New Haven, CT 06520 USA.
[Tagare, Hemant D.; Fulbright, Robert K.] Yale Univ, Dept Diagnost Radiol, New Haven, CT 06520 USA.
[Long, Rodney; Antani, Sameer] Natl Lib Med, Bethesda, MD 20894 USA.
RP Qian, XN (reprint author), Yale Univ, Dept Elect Engn, New Haven, CT 06520 USA.
EM xiaoning.qian@gmail.com
RI Qian, Huiping/E-8264-2010;
OI Antani, Sameer/0000-0002-0040-1387
FU National Library of Medicine [R01-LM06911-05]
FX We would like to thank the anonymous reviewers for their valuable and
constructive comments. This research was support by the Grant
R01-LM06911-05 from the National Library of Medicine.
NR 53
TC 8
Z9 9
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1361-8415
J9 MED IMAGE ANAL
JI Med. Image Anal.
PD JUN
PY 2010
VL 14
IS 3
BP 243
EP 254
DI 10.1016/j.media.2010.01.001
PG 12
WC Computer Science, Artificial Intelligence; Computer Science,
Interdisciplinary Applications; Engineering, Biomedical; Radiology,
Nuclear Medicine & Medical Imaging
SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical
Imaging
GA 604CW
UT WOS:000278255900001
PM 20163981
ER
PT J
AU Fan, TWM
Yuan, PX
Lane, AN
Higashi, RM
Wang, Y
Hamidi, AB
Zhou, RL
Guitart, X
Chen, G
Manji, HK
Kaddurah-Daouk, R
AF Fan, Teresa W-M
Yuan, Peixiong
Lane, Andrew N.
Higashi, Richard M.
Wang, Yun
Hamidi, Anahita B.
Zhou, Rulun
Guitart, Xavier
Chen, Guang
Manji, Husseini K.
Kaddurah-Daouk, Rima
TI Stable isotope-resolved metabolomic analysis of lithium effects on
glial-neuronal metabolism and interactions
SO METABOLOMICS
LA English
DT Article
DE Bipolar disorder; Lithium; C-13-labeled tracers; Astrocytes; Neurons;
Pyruvate carboxylation; Glu/Gln cycling
ID BRAIN GLUCOSE-METABOLISM; MAGNETIC-RESONANCE-SPECTROSCOPY; RAT-BRAIN;
ENERGY-METABOLISM; MOOD DISORDERS; AMINO-ACIDS; IN-VIVO; ASTROCYTES;
LACTATE; ACTIVATION
AB Despite the long-established therapeutic efficacy of lithium in the treatment of bipolar disorder (BPD), its molecular mechanism of action remains elusive. Newly developed stable isotope-resolved metabolomics (SIRM) is a powerful approach that can be used to elucidate systematically how lithium impacts glial and neuronal metabolic pathways and activities, leading ultimately to deciphering its molecular mechanism of action. The effect of lithium on the metabolism of three different C-13-labeled precursors ([U-C-13]-glucose, C-13-3-lactate or C-13-2,3-alanine) was analyzed in cultured rat astrocytes and neurons by nuclear magnetic resonance (NMR) spectroscopy and gas chromatography mass spectrometry (GC-MS). Using [U-C-13]-glucose, lithium was shown to enhance glycolytic activity and part of the Krebs cycle activity in both astrocytes and neurons, particularly the anaplerotic pyruvate carboxylation (PC). The PC pathway was previously thought to be active in astrocytes but absent in neurons. Lithium also stimulated the extracellular release of C-13 labeled-lactate, -alanine (Ala), -citrate, and -glutamine (Gln) by astrocytes. Interrogation of neuronal pathways using C-13-3-lactate or C-13-2,3-Ala as tracers indicated a high capacity of neurons to utilize lactate and Ala in the Krebs cycle, particularly in the production of labeled Asp and Glu via PC and normal cycle activity. Prolonged lithium treatment enhanced lactate metabolism via PC but inhibited lactate oxidation via the normal Krebs cycle in neurons. Such lithium modulation of glycolytic, PC and Krebs cycle activity in astrocytes and neurons as well as release of fuel substrates by astrocytes should help replenish Krebs cycle substrates for Glu synthesis while meeting neuronal demands for energy. Further investigations into the molecular regulation of these metabolic traits should provide new insights into the pathophysiology of mood disorders and early diagnostic markers, as well as new target(s) for effective therapies.
C1 [Kaddurah-Daouk, Rima] Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA.
[Fan, Teresa W-M; Lane, Andrew N.; Higashi, Richard M.] Univ Louisville, Dept Chem, Ctr Regulatory & Environm Analyt Metabol, Louisville, KY 40292 USA.
[Yuan, Peixiong; Wang, Yun; Hamidi, Anahita B.; Zhou, Rulun; Guitart, Xavier; Chen, Guang; Manji, Husseini K.] NIMH, Biomarker Lab, Mol Pathophysiol Lab, Mood & Anxiety Disorder Program,NIH, Bethesda, MD 20892 USA.
[Fan, Teresa W-M; Lane, Andrew N.; Higashi, Richard M.] Univ Louisville, Dept Med, Struct Biol Program, James Graham Brown Canc Ctr, Louisville, KY 40202 USA.
[Manji, Husseini K.] Johnson & Johnson Consumer Prod Inc, Titusville, NJ USA.
[Fan, Teresa W-M] Univ Louisville, Dept Chem, Louisville, KY 40208 USA.
RP Kaddurah-Daouk, R (reprint author), Duke Univ, Med Ctr, Dept Psychiat, Box 3950, Durham, NC 27710 USA.
EM twmfan@gmail.com; kaddu001@mc.duke.edu
RI Chen, Guang/A-2570-2017
FU NIH, National Center for Research Resources [P20RR018733,
1R01CA118434-01A2, 3R01CA118434-02S1, R24GM078233]; National Science
Foundation [EPS-0447479]
FX NMR spectra were recorded at the JG Brown Cancer Center NMR facility,
and mass spectra were obtained from the Center for Regulatory and
Environmental Analytical Metabolomics (CREAM) facility at the University
of Louisville. Ioline Henter of NIMH provided invaluable editorial
assistance. Financial support: The study was supported in part by NIH
Grant Numbers P20RR018733 from the National Center for Research
Resources, 1R01CA118434-01A2 (TF, ANL, RMH), 3R01CA118434-02S1 (TF,
RMH), and R24GM078233 (RKD, TF) and National Science Foundation EPSCoR
grant # EPS-0447479 (TF, ANL).
NR 59
TC 32
Z9 32
U1 0
U2 12
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1573-3882
EI 1573-3890
J9 METABOLOMICS
JI Metabolomics
PD JUN
PY 2010
VL 6
IS 2
BP 165
EP 179
DI 10.1007/s11306-010-0208-9
PG 15
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 591KG
UT WOS:000277298700001
PM 20631920
ER
PT J
AU Kalab, P
Soderholm, J
AF Kalab, Petr
Soderholm, Jon
TI The design of Forster (fluorescence) resonance energy transfer
(FRET)-based molecular sensors for Ran GTPase
SO METHODS
LA English
DT Review
DE FRET; Forster; Fluorescence; Sensor; FLIM; GFP; Ran GTPase; Importin
beta; IBB; RanBP1
ID LIFETIME IMAGING MICROSCOPY; PROTEIN-PROTEIN INTERACTIONS; FRET-BASED
BIOSENSORS; IMPORTIN-BETA; LIVING CELLS; IN-VIVO;
CONFORMATIONAL-CHANGES; MITOTIC SPINDLE; NUCLEAR IMPORT;
SCHIZOSACCHAROMYCES-POMBE
AB The application of FRET-based molecular biosensors provided confirmation of the central model of Ran GTPase function and led to important new insights into its physiological role. In many fields of cell biology, methods employing FRET are a standard approach that is becoming increasingly accessible due to advances in instrumentation and available fluorophores. However, the optimal design of a FRET sensor remains to be the cornerstone of any successful FRET application. Utilizing the recent literature on FRET applications and our studies on Ran, we outline the basic considerations involved in designing molecular FRET sensors. We point to several broadly applicable principles that were used in many different FRET sensors that can detect a wide range of molecular events. Using the FRET sensors for Ran that we created as examples, we then focus on the practical aspects of FRET assays. We describe the preparation of a bipartite FRET sensor consisting of ECFP-Ran and EYFP-importin beta and its validation as a reporter for FRET-based high throughput screening in small molecule libraries. Finally, we review the design and optimization of monomolecular FRET sensors that monitor the RanGTP-RanBP1 interaction, and of sensors detecting the RanGTP-regulated importin beta cargo release. Published by Elsevier Inc.
C1 [Kalab, Petr] NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Soderholm, Jon] Yonsei Univ, Dept Biotechnol, Seoul 120749, South Korea.
RP Kalab, P (reprint author), NCI, Cellular & Mol Biol Lab, NIH, 37 Convent Dr,MSC 4256,Bldg 37,Room 2050, Bethesda, MD 20892 USA.
EM kalab@mail.nih.gov
RI Kalab, Petr/B-2478-2009
FU NIH [RO1GM065232]
FX All the experimental work in this paper was supported by NIH grant
RO1GM065232 and was performed in the laboratories of Dr. Karsten Weis
and Dr. Rebecca Heald at the University of California at Berkeley,
Berkeley, California.
NR 118
TC 12
Z9 13
U1 1
U2 39
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1046-2023
EI 1095-9130
J9 METHODS
JI Methods
PD JUN
PY 2010
VL 51
IS 2
BP 220
EP 232
DI 10.1016/j.ymeth.2010.01.022
PG 13
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 615GC
UT WOS:000279121300006
PM 20096786
ER
PT J
AU Graves, SF
Kobayashi, SD
Braughton, KR
Diep, BA
Chambers, HF
Otto, M
DeLeo, FR
AF Graves, Shawna F.
Kobayashi, Scott D.
Braughton, Kevin R.
Diep, Binh An
Chambers, Henry F.
Otto, Michael
DeLeo, Frank R.
TI Relative contribution of Panton-Valentine leukocidin to PMN plasma
membrane permeability and lysis caused by USA300 and USA400 culture
supernatants
SO MICROBES AND INFECTION
LA English
DT Article
DE Staphylococcus aureus; Virulence; Leukocidins
ID RESISTANT STAPHYLOCOCCUS-AUREUS; HUMAN POLYMORPHONUCLEAR LEUKOCYTES;
HUMAN NEUTROPHILS; VIRULENCE; LEUCOCIDIN; PNEUMONIA; TOXIN;
IDENTIFICATION; PURIFICATION; INFECTIONS
AB Panton-Valentine leukocidin (PVL) is a cytolytic toxin associated with severe community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections. However, the relative contribution of PVL to host cell lysis during CA-MRSA infection remains unknown. Here we investigated the relative contribution of PVL to human polymorphonuclear leukocyte (PMN) plasma membrane permeability and lysis in vitro by using culture supernatants from wild-type and isogenic lukS/F-PV negative (Delta pvl) USA300 and USA400 strains. Using S. aureus culture conditions that favor selective high production of PVL (CCY medium), there was on average more PMN plasma membrane permeability and cell lysis caused by supernatants derived from wild-type strains compared with those from Delta pvl strains. Unexpectedly, plasma membrane permeability did not necessarily correlate with ultimate cell lysis. Moreover, the level of pore formation caused by culture supernatants varied dramatically (e.g., range was 0.32-99.09% for wild-type USA300 supernatants at 30 min) and was not attributable to differences in PMN susceptibility to PVL among human blood donors. We conclude that PMN pore formation assays utilizing S. aureus culture supernatants have limited ability to estimate the relative contribution of PVL to pathogenesis (or cytolysis in vitro or in vivo), especially when assayed using culture media that promote selective high production of PVL. Published by Elsevier Masson SAS.
C1 [Graves, Shawna F.; Kobayashi, Scott D.; Braughton, Kevin R.; DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Graves, Shawna F.] Univ Montana, Div Biol Sci, Dept Biochem & Biophys, Missoula, MT 59812 USA.
[Diep, Binh An; Chambers, Henry F.] Univ Calif San Francisco, Dept Med, Div Infect Dis, San Francisco, CA USA.
[Otto, Michael] NIAID, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA.
RP DeLeo, FR (reprint author), NIAID, Lab Human Bacterial 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; Otto, Michael/0000-0002-2222-4115
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX This article was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 37
TC 26
Z9 26
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1286-4579
J9 MICROBES INFECT
JI Microbes Infect.
PD JUN
PY 2010
VL 12
IS 6
BP 446
EP 456
DI 10.1016/j.micinf.2010.02.005
PG 11
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 614GY
UT WOS:000279044800004
PM 20172045
ER
PT J
AU Whirledge, S
Cidlowski, JA
AF Whirledge, S.
Cidlowski, J. A.
TI Glucocorticoids, stress, and fertility
SO MINERVA ENDOCRINOLOGICA
LA English
DT Review
DE Glucocorticoids; Hypothalamus; Pituitary gland; Ovary; Uterus
ID FOLLICLE-STIMULATING-HORMONE; BETA-HYDROXYSTEROID DEHYDROGENASE; RAT
LEYDIG-CELLS; PITUITARY-ADRENAL-FUNCTION; SURFACE EPITHELIAL-CELLS;
GRANULOSA-LUTEIN CELLS; 11-BETA-HYDROXYSTEROID DEHYDROGENASE; PRENATAL
STRESS; GONADOTROPIN-SECRETION; MESSENGER-RNA
AB Modifications of the hypothalamo-pituitary-adrenal axis and associated changes in circulating levels of glucocorticoids form a key component of the response of an organism to stressful challenges. Increased levels of glucocorticoids promote gluconeogenesis, mobilization of amino acids, and stimulation of fat breakdown to maintain circulating levels of glucose necessary to mount a stress response. In addition to profound changes in the physiology and function of multiple tissues, stress and elevated glucocorticoids can also inhibit reproduction, a logical effect for the survival of self. Precise levels of glucocorticoids are required for proper gonadal function; where the balance is disrupted, so is fertility. Glucocorticoids affect gonadal function at multiple levels in hypothalamo-pituitary-gonadal axis: 1) the hypothalamus (to decrease the synthesis and release of gonadotropin-releasing hormone [GnRH]; 2) the pituitary gland (to inhibit the synthesis and release of luteinizing hormone [LH] and follicle stimulating hormone [FSH]); 3) the testis/ovary (to modulate steroidogenesis and/or gametogenesis directly). Furthermore, maternal exposure to prenatal stress or exogenous glucocorticoids can lead to permanent modification of hypothalamo-pituitary-adrenal function and stress-related behaviors in offspring. Glucocorticoids are vital to many aspects of normal brain development, but fetal exposure to superabundant glucocorticoids can result in life-long effects on neuroendocrine function. This review focuses on the molecular mechanisms believed to mediate glucocorticoid inhibition of reproductive functions and the anatomical sites at which these effects take place.
C1 [Whirledge, S.; Cidlowski, J. A.] Natl Inst Environm Hlth Sci, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Durham, NC USA.
RP Cidlowski, JA (reprint author), NIEHS, NIH, MD F3-07,POB 12233, Res Triangle Pk, NC 27709 USA.
EM cidlows1@niehs.nih.gov
FU NIH National Institute of Environmental Health Sciences
FX We gratefully acknowledge Dr. Robert Oakley for discussion and
assistance with manuscript preparation. This research was supported by
the Intramural Research Program of the NIH National Institute of
Environmental Health Sciences.
NR 105
TC 52
Z9 54
U1 3
U2 25
PU EDIZIONI MINERVA MEDICA
PI TURIN
PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY
SN 0391-1977
J9 MINERVA ENDOCRINOL
JI Minerva Endocrinol.
PD JUN
PY 2010
VL 35
IS 2
BP 109
EP 125
PG 17
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 626YN
UT WOS:000280004600007
PM 20595939
ER
PT J
AU Scott, I
AF Scott, Iain
TI The role of mitochondria in the mammalian antiviral defense system
SO MITOCHONDRION
LA English
DT Review
DE MAVS; Innate immunity; NLRX1; STING; Mitochondria; Apoptosis
ID NF-KAPPA-B; HEPATITIS-C VIRUS; RIG-I; INNATE IMMUNITY; ADAPTER PROTEIN;
SIGNALING PROTEIN; MAVS; APOPTOSIS; RESPONSES; NLRX1
AB Innate immunity is a crucial defense system against viral and bacterial pathogens, providing a rapid response to mitigate the effects of microbial attack. While more readily associated with respiration and metabolism, recent research has surprisingly identified a number of mitochondrial factors in the mammalian innate immune system. This review summarizes the novel mitochondrial proteins, such as MAVS and NLRX1, involved in this process and attempts to reconcile this new mitochondrial function with our previous knowledge of the organelle. Published by Elsevier B.V.
C1 NHLBI, Mol Biol Sect, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
RP Scott, I (reprint author), NHLBI, Mol Biol Sect, Translat Med Branch, NIH, 10 CRC,Room 5-3216,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM scotti@mail.nih.gov
FU National Heart, Lung and Blood Institute, National Institutes of Health;
NINDS, NIH
FX The author would like to thank Michael Sack (NHLBI, NIH) and Richard J.
Youle (NINDS, NIH) for their help and support. The author would also
like to thank the two anonymous reviewers who suggested improvements to
this manuscript. This research was supported by the intramural research
program of the National Heart, Lung and Blood Institute, National
Institutes of Health.
NR 48
TC 32
Z9 36
U1 2
U2 12
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 JUN
PY 2010
VL 10
IS 4
BP 316
EP 320
DI 10.1016/j.mito.2010.02.005
PG 5
WC Cell Biology; Genetics & Heredity
SC Cell Biology; Genetics & Heredity
GA 604FL
UT WOS:000278262600002
PM 20206303
ER
PT J
AU Rizzo, KA
Streubel, B
Pittaluga, S
Chott, A
Xi, LQ
Raffeld, M
Jaffe, ES
AF Rizzo, Kathryn A.
Streubel, Berthold
Pittaluga, Stefania
Chott, Andreas
Xi, Liqiang
Raffeld, Mark
Jaffe, Elaine S.
TI Marginal zone lymphomas in children and the young adult population;
characterization of genetic aberrations by FISH and RT-PCR
SO MODERN PATHOLOGY
LA English
DT Article
DE marginal zone lymphoma; pediatric; genetic aberrations
ID B-CELL LYMPHOMA; HELICOBACTER-PYLORI ERADICATION; PRIMARY FOLLICULAR
LYMPHOMA; MALT LYMPHOMA; TISSUE LYMPHOMA; DIFFERENT SITES; HYPERPLASIA;
CHILDHOOD; TRANSLOCATIONS; ABNORMALITIES
AB Marginal zone lymphomas present rarely in children and young adults as either primary nodal or extranodal disease and have an excellent prognosis. To date, chromosomal aberrations have not been analyzed in the pediatric and young adult population. We undertook a study to analyze genetic alterations in nodal and extranodal marginal zone lymphomas in children and young adults using fluorescence in situ hybridization (FISH) and RT-PCR. These findings were correlated with clinical features at presentation and immunophenotype. Forty-one cases were identified meeting these criteria. The age range was 1.5-29 years old with 49% of the cases <18 years of age. 73% of the marginal zone lymphoma cases showed evidence of light chain restriction by immunohistochemistry or flow cytometry. CD43 was coexpressed in 83%. 85% of the marginal zone lymphoma cases tested showed evidence of immunoglobulin heavy chain gene rearrangement. Fifty-nine percent of the cases were nodal marginal zone lymphomas with a median age at presentation of 16 years and an M/F ratio of 7:1. Twenty-one percent of the nodal marginal zone lymphoma cases contained genetic aberrations. Seventeen percent contained trisomy 18 with one case containing an additional trisomy 3. A translocation of the immunoglobulin heavy chain gene to an unknown partner gene was present in one case. Forty-one percent of the cases were extranodal marginal zone lymphomas with a median age of 24 years and a M/F ratio of 1.4:1. Eighteen percent of the extranodal marginal zone lymphoma cases contained genetic aberrations. The t(14;18) involving the IGH and MALT1 genes was present in one case, tetraploidy was present in one case, and another case contained trisomy 3. Overall the incidence of genetic aberrations in marginal zone lymphomas in the pediatric and young adult population is low, but the aberrations seen are similar to those seen in the adult population. Modern Pathology (2010) 23, 866-873; doi:10.1038/modpathol.2010.63; published online 19 March 2010
C1 [Jaffe, Elaine S.] Med Univ Vienna, Dept Pathol, NCI, Hematopathol Sect,Lab Pathol,Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Chott, Andreas] Vienna Gen Hosp, Dept Pathol, Vienna, Austria.
[Streubel, Berthold] Med Univ Vienna, Dept Pathol, Vienna, Austria.
RP Jaffe, ES (reprint author), Med Univ Vienna, Dept Pathol, NCI, Hematopathol Sect,Lab Pathol,Ctr Canc Res,NIH, 10 Ctr Dr,Room 2B 42, Bethesda, MD 20892 USA.
EM elainejaffe@nih.gov
OI Jaffe, Elaine/0000-0003-4632-0301
NR 29
TC 26
Z9 27
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD JUN
PY 2010
VL 23
IS 6
BP 866
EP 873
DI 10.1038/modpathol.2010.63
PG 8
WC Pathology
SC Pathology
GA 604GG
UT WOS:000278266800011
PM 20305621
ER
PT J
AU Lehmann, P
Salzberger, B
Haerle, P
Aksentijevich, I
Kastner, D
Schoelmerich, J
Rosenfeld, S
Mueller-Ladner, U
AF Lehmann, Petra
Salzberger, Bernd
Haerle, Peter
Aksentijevich, Ivona
Kastner, Daniel
Schoelmerich, Juergen
Rosenfeld, Stephanie
Mueller-Ladner, Ulf
TI Variable intrafamilial expressivity of the rare tumor necrosis
factor-receptor associated periodic syndrome-associated mutation I170N
that affects the TNFR1A cleavage site
SO MODERN RHEUMATOLOGY
LA English
DT Article
DE Hereditary fever syndrome; Tumor necrosis factor-receptor associated
periodic syndrome; Etanercept; Amyloidosis
ID SYNDROME TRAPS; MONOCYTIC FASCIITIS; RENAL AMYLOIDOSIS; ETANERCEPT;
FEVER; TNFRSF1A; PATHOGENESIS; EPISODES; THERAPY; FAILURE
AB We report on a 33-year-old female patient with a relatively mild clinical case of TNF-receptor associated periodic syndrome (TRAPS) and her 58-year-old father in whom end-stage renal disease due to TRAPS-related AA-amyloidosis has already developed. TRAPS was caused by a I170N mutation that has previously not been associated with amyloidosis. It remains unclear if an only mildly affected patient such as ours would benefit from treatment considering her father's severe course of disease. The relevant literature on this problem is reviewed.
C1 [Lehmann, Petra] Univ Med Ctr Regensburg, Dept Internal Med 1, D-93042 Regensburg, Germany.
[Salzberger, Bernd; Haerle, Peter; Schoelmerich, Juergen; Rosenfeld, Stephanie] Univ Clin Regensburg, Dept Internal Med 1, Regensburg, Germany.
[Aksentijevich, Ivona; Kastner, Daniel] NIH, Bethesda, MD 20892 USA.
[Mueller-Ladner, Ulf] Univ Giessen, Dept Rheumatol, Kerckhoff Klin, Giessen, Germany.
RP Lehmann, P (reprint author), Univ Med Ctr Regensburg, Dept Internal Med 1, Franz Josef Str Allee 11, D-93042 Regensburg, Germany.
EM petra.lehmann@klinik.uni-regensburg.de
FU Intramural NIH HHS [ZIA AR041185-01, Z01 AR041170-01, ZIA AR041153-05,
ZIA AR041139-07, Z01 AR041139-06, ZIA AR041138-07, Z01 AR041139-05, ZIE
AR041176-02, Z01 AR041083-18, Z01 AR041138-06, ZIA AR041170-02, ZIA
AR041083-20, Z01 AR041180-01, ZIA AR041162-02, Z01 AR041153-04, Z01
AR041176-01, ZID AR041180-02, Z01 AR041123-09, Z01 AR041083-19, ZIA
AR041123-11, Z01 AR041123-10]
NR 27
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1439-7595
EI 1439-7609
J9 MOD RHEUMATOL
JI Mod. Rheumatol.
PD JUN
PY 2010
VL 20
IS 3
BP 311
EP 315
DI 10.1007/s10165-010-0273-y
PG 5
WC Rheumatology
SC Rheumatology
GA 607FK
UT WOS:000278484300016
PM 20169391
ER
PT J
AU Kassis, JA
Kennison, JA
AF Kassis, Judith A.
Kennison, James A.
TI Recruitment of Polycomb Complexes: a Role for SCM
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Editorial Material
ID RESPONSE ELEMENTS; REPRESSION; DROSOPHILA; PROTEINS; BINDING; DNA
C1 [Kassis, Judith A.; Kennison, James A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, Bethesda, MD 20892 USA.
RP Kassis, JA (reprint author), NICHD, Program Genom Differentiat, Bldg 6B Room 3B-331,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jkassis@mail.nih.gov
OI Kassis, Judith/0000-0001-9268-3213
NR 14
TC 3
Z9 3
U1 0
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD JUN
PY 2010
VL 30
IS 11
BP 2581
EP 2583
DI 10.1128/MCB.00231-10
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 594SQ
UT WOS:000277558300001
PM 20351178
ER
PT J
AU Donninger, H
Hesson, L
Vos, M
Beebe, K
Gordon, L
Sidransky, D
Liu, JW
Schlegel, T
Payne, S
Hartmann, A
Latif, F
Clark, GJ
AF Donninger, Howard
Hesson, Luke
Vos, Michele
Beebe, Kristin
Gordon, Laura
Sidransky, David
Liu, Jun Wei
Schlegel, Thomas
Payne, Shannon
Hartmann, Arndt
Latif, Farida
Clark, Geoffrey J.
TI The Ras Effector RASSF2 Controls the PAR-4 Tumor Suppressor
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID PROTEIN PAR-4; K-RAS; EPIGENETIC INACTIVATION; PROSTATE-CANCER;
GASTRIC-CANCER; CELL CARCINOMA; APOPTOSIS; GENE; HYPERMETHYLATION;
EXPRESSION
AB RASSF2 is a novel proapoptotic effector of K-Ras. Inhibition of RASSF2 expression enhances the transforming effects of K-Ras, and epigenetic inactivation of RASSF2 is frequently detected in mutant Ras-containing primary tumors. Thus, RASSF2 is implicated as a tumor suppressor whose inactivation facilitates transformation by disconnecting apoptotic responses from Ras. The mechanism of action of RASSF2 is not known. Here we show that RASSF2 forms a direct and endogenous complex with the prostate apoptosis response protein 4 (PAR-4) tumor suppressor. This interaction is regulated by K-Ras and is essential for the full apoptotic effects of PAR-4. RASSF2 is primarily a nuclear protein, and shuttling of PAR-4 from the cytoplasm to the nucleus is essential for its function. We show that RASSF2 modulates the nuclear translocation of PAR-4 in prostate tumor cells, providing a mechanism for its biological effects. Thus, we identify the first tumor suppressor signaling pathway emanating from RASSF2, we identify a novel mode of action of a RASSF protein, and we provide an explanation for the extraordinarily high frequency of RASSF2 inactivation we have observed in primary prostate tumors.
C1 [Donninger, Howard; Gordon, Laura; Clark, Geoffrey J.] Univ Louisville, Mol Targets Program, James Graham Brown Canc Ctr, Dept Med, Louisville, KY 40202 USA.
[Hesson, Luke; Latif, Farida] Univ Birmingham, Sect Med & Mol Genet, Birmingham B15 2TT, W Midlands, England.
[Vos, Michele; Beebe, Kristin] NCI, Cell & Canc Biol Branch, Rockville, MD USA.
[Sidransky, David; Liu, Jun Wei] Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Head & Neck Canc Res Div, Baltimore, MD 21205 USA.
[Schlegel, Thomas; Payne, Shannon] Univ Erlangen Nurnberg, Dept Pathol, D-91054 Erlangen, Germany.
[Hartmann, Arndt] Epigenom Inc, Seattle, WA 98101 USA.
RP Clark, GJ (reprint author), Univ Louisville, Mol Targets Program, James Graham Brown Canc Ctr, Dept Med, 505 S Hancock St, Louisville, KY 40202 USA.
EM gjclar01@louisville.edu
FU NIH [1P20 RR18733]; NCI; Breast Cancer Campaign, Cancer Research UK
FX We thank Vivek Rangnekar (University of Kentucky, Lexington) for
reagents and advice, Manuel Serrano and Pablo Fernandez-Marcos (Spanish
National Cancer Research Center) for unpublished negative data, and Nina
Niessl and Monika Kerscher for excellent technical assistance in
processing the tissue specimens. This work was funded in part by NIH
grant 1P20 RR18733, NCI intramural funds (G.J.C.), and the Breast Cancer
Campaign, Cancer Research UK (F.L.).
NR 49
TC 14
Z9 18
U1 1
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD JUN
PY 2010
VL 30
IS 11
BP 2608
EP 2620
DI 10.1128/MCB.00208-09
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 594SQ
UT WOS:000277558300004
PM 20368356
ER
PT J
AU Lee, S
Shuman, JD
Guszczynski, T
Sakchaisri, K
Sebastian, T
Copeland, TD
Miller, M
Cohen, MS
Taunton, J
Smart, RC
Xiao, Z
Yu, LR
Veenstra, TD
Johnson, PF
AF Lee, Sook
Shuman, Jon D.
Guszczynski, Tad
Sakchaisri, Krisada
Sebastian, Thomas
Copeland, Terry D.
Miller, Maria
Cohen, Michael S.
Taunton, Jack
Smart, Robert C.
Xiao, Zhen
Yu, Li-Rong
Veenstra, Timothy D.
Johnson, Peter F.
TI RSK-Mediated Phosphorylation in the C/EBP beta Leucine Zipper Regulates
DNA Binding, Dimerization, and Growth Arrest Activity
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID MITOTIC CLONAL EXPANSION; ONCOGENE-INDUCED SENESCENCE; PROTEIN-BETA;
TRANSCRIPTIONAL ACTIVATOR; HEPATOCYTE PROLIFERATION; CELL PROLIFERATION;
NUCLEAR FACTOR; MAMMARY-GLAND; DIFFERENTIATION; ADIPOGENESIS
AB The bZIP transcription factor C/EBP beta is a target of Ras signaling that has been implicated in Ras-induced transformation and oncogene-induced senescence (OIS). To gain insights into Ras-C/EBP beta signaling, we investigated C/EBP beta activation by oncogenic Ras. We show that C/EBP beta DNA binding is autorepressed and becomes activated by the Ras-Raf-MEK-ERK-p90(RSK) cascade. Inducible phosphorylation by RSK on Ser273 in the leucine zipper was required for DNA binding. In addition, three other modifications (phosphorylation on Tyr109 [p-Tyr109], p-Ser111, and monomethylation of Arg114 [me-Arg114]) within an N-terminal autoinhibitory domain were important for Ras-induced C/EBP beta activation and cytostatic activity. Apart from its role in DNA binding, Ser273 phosphorylation also creates an interhelical g <-> e ' salt bridge with Lys268 that increases attractive electrostatic interactions between paired leucine zippers and promotes homodimerization. Mutating Ser273 to Ala or Lys268 to Glu decreased C/EBP beta homodimer formation, whereas heterodimerization with C/EBP gamma was relatively unaffected. The S273A substitution also reduced the antiproliferative activity of C/EBP beta in Ras(V12)-expressing fibroblasts and decreased binding to target cell cycle genes, while a phosphomimetic substitution (S273D) maintained growth arrest function. Our findings identify four novel C/EBP beta-activating modifications, including RSK-mediated phosphorylation of a bifunctional residue in the leucine zipper that regulates DNA binding and homodimerization and thereby promotes cell cycle arrest.
C1 [Lee, Sook; Shuman, Jon D.; Sakchaisri, Krisada; Sebastian, Thomas; Johnson, Peter F.] NCI, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21702 USA.
[Guszczynski, Tad; Copeland, Terry D.] NCI, Lab Cell & Dev Signaling, Ctr Canc Res, Frederick, MD 21702 USA.
[Miller, Maria] NCI, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Cohen, Michael S.; Taunton, Jack] Univ Calif San Francisco, Program Chem & Chem Biol, San Francisco, CA 94143 USA.
[Cohen, Michael S.; Taunton, Jack] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA.
[Smart, Robert C.] N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA.
[Xiao, Zhen; Yu, Li-Rong; Veenstra, Timothy D.] SAIC Frederick Inc, Adv Technol Program, Lab Prote & Analyt Technol, Frederick, MD 21702 USA.
RP Johnson, PF (reprint author), NCI, Lab Canc Prevent, Ctr Canc Res, Bldg 539,Room 122, Frederick, MD 21702 USA.
EM johnsope@mail.nih.gov
RI Johnson, Peter/A-1940-2012; Miller, Maria/I-1636-2013;
OI Johnson, Peter/0000-0002-4145-4725; Miller, Maria/0000-0003-0252-5348;
Shuman, Jon/0000-0001-8412-9087
FU NIH, National Cancer Institute, Center for Cancer Research
[N01-CO-12400]
FX We thank the individuals mentioned in the text for generously providing
plasmids and antibodies, Suzanne Specht for assistance with
phosphopeptide mapping, Barb Shankle and Nancy Martin for genotyping and
preparation of MEFs, Angie Hackley for animal handling, and Jiro Wada
and Allan Kane for preparing figures.; We dedicate this paper to the
memory of Barb Shankle. This research was supported by the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research, and 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.
NR 50
TC 30
Z9 31
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD JUN
PY 2010
VL 30
IS 11
BP 2621
EP 2635
DI 10.1128/MCB.00782-09
PG 15
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 594SQ
UT WOS:000277558300005
PM 20351173
ER
PT J
AU Loots, GG
Ovcharenko, I
AF Loots, Gabriela G.
Ovcharenko, Ivan
TI Human Variation in Short Regions Predisposed to Deep Evolutionary
Conservation
SO MOLECULAR BIOLOGY AND EVOLUTION
LA English
DT Article
DE gene regulation; enhancer evolution; selection and adaptation; sequence
conservation
ID GENE DESERTS; SEQUENCE COMPARISONS; NONCODING SEQUENCES; DISEASE RISK;
EXPRESSION; VERTEBRATE; ENHANCER; ELEMENTS; DATABASE; GENOMES
AB The landscape of the human genome consists of millions of short islands of conservation that are 100% conserved across multiple vertebrate genomes (termed "bricks"), the majority of which are located in noncoding regions. Several hundred thousand bricks are deeply conserved reaching the genomes of amphibians and fish. Deep phylogenetic conservation of noncoding DNA has been reported to be strongly associated with the presence of gene regulatory elements, introducing bricks as a proxy to the functional noncoding landscape of the human genome. Here, we report a significant overrepresentation of bricks in the promoters of transcription factors and developmental genes, where the high level of phylogenetic conservation correlates with an increase in brick overrepresentation. We also found that the presence of a brick dictates a predisposition to evolutionary constraint, with only 0.7% of the amniota brick central nucleotides being diverged within the primate lineage-an 11-fold reduction in the divergence rate compared with random expectation. Human single-nucleotide polymorphism (SNP) data explains only 3% of primate-specific variation in amniota bricks, thus arguing for a widespread fixation of brick mutations within the primate lineage and prior to human radiation. This variation, in turn, might have been utilized as a driving force for primate- and hominoid-specific adaptation. We also discovered a pronounced deviation from the evolutionary predisposition in the human lineage, with over 20-fold increase in the substitution rate at brick SNP sites over expected values. In addition, contrary to typical brick mutations, brick variation commonly encountered in the human population displays limited, if any, signatures of negative selection as measured by the minor allele frequency and population differentiation (F-statistical measure) measures. These observations argue for the plasticity of gene regulatory mechanisms in vertebrates-with evidence of strong purifying selection acting on the gene regulatory landscape of the human genome, where widespread advantageous mutations in putative regulatory elements are likely utilized in functional diversification and adaptation of species.
C1 [Ovcharenko, Ivan] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Loots, Gabriela G.] Lawrence Livermore Natl Lab, Biol & Biotechnol Div, Phys & Life Sci Directorate, Livermore, CA USA.
RP Ovcharenko, I (reprint author), NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
EM ovcharei@ncbi.nlm.nih.gov
FU National Institutes of Health (NIH) [HG00396]; U.S. Department of Energy
[DE-AC52-07NA27344]; National Library of Medicine, NIH
FX G. G. L. was supported by National Institutes of Health (NIH) grant
HG003963. This work was performed under the auspices of the U.S.
Department of Energy by Lawrence Livermore National Laboratory under
Contract DE-AC52-07NA27344. I.O. was supported by the Intramural
Research Program of the National Library of Medicine, NIH.
NR 41
TC 6
Z9 6
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0737-4038
J9 MOL BIOL EVOL
JI Mol. Biol. Evol.
PD JUN
PY 2010
VL 27
IS 6
BP 1279
EP 1288
DI 10.1093/molbev/msq011
PG 10
WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
Heredity
GA 600MX
UT WOS:000277991900007
PM 20093432
ER
PT J
AU Li, G
Liu, JH
Abu-Asab, M
Masabumi, S
Maru, Y
AF Li, Guang
Liu, Juhong
Abu-Asab, Mones
Masabumi, Shibuya
Maru, Yoshiro
TI XPB Induces C1D Expression to Counteract UV-Induced Apoptosis
SO MOLECULAR CANCER RESEARCH
LA English
DT Article
ID TRANSCRIPTION FACTOR TFIIH; RIBOSOMAL-PROTEIN S3; C-MYC EXPRESSION;
XERODERMA-PIGMENTOSUM; DNA-REPAIR; EXCISION-REPAIR; COCKAYNE-SYNDROME;
REPAIR/TRANSCRIPTION FACTOR; HELICASE; PROMOTER
AB Although C1D has been shown to be involved in DNA double-strand break repair, how C1D expression was induced and the mechanism(s) by which C1D facilitates DNA repair in mammalian cells remain poorly understood. We and others have previously shown that expression of xeroderma pigmentosum B (XPB) protein efficiently compensated the UV irradiation-sensitive phenotype of 27-1 cells, which lack functional XPB. To further explore XPB-regulated genes that could be involved in UV-induced DNA repair, differential display analysis of mRNA levels from CHO-9, 27-1, and 27-1 complemented with wild-type XPB was done and C1D gene was identified as one of the major genes whose expression was significantly upregulated by restoring XPB function. We found that XPB is essential to induce C1D transcription after UV irradiation. The increase in C1D expression effectively compensates for the UV-induced proteolysis of C1D and thus maintains cellular C1D level to cope with DNA damage inflicted by UV irradiation. We further showed that although insufficient to rescue 27-1 cells from UV-induced apoptosis by itself, C1D facilitates XPB DNA repair through direct interaction with XPB. Our findings provided direct evidence that C1D is associated with DNA repair complex and may promote repair of UV-induced DNA damage. Mol Cancer Res; 8(6); 885-95. (C) 2010 AACR.
C1 [Li, Guang] NCI, Pediat Tumor Biol & Ultra Struct Pathol Sect, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Liu, Juhong] US FDA, Chem Lab, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA.
[Masabumi, Shibuya] Tokyo Med & Dent Univ, Dept Mol Oncol, Tokyo, Japan.
[Maru, Yoshiro] Tokyo Womens Med Univ, Dept Pharmacol, Tokyo, Japan.
RP Li, G (reprint author), NCI, Pediat Tumor Biol & Ultra Struct Pathol Sect, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
EM liguan1@mail.nih.gov
OI Abu-Asab, Mones/0000-0002-4047-1232
FU Intramural NIH HHS [Z99 CA999999]
NR 36
TC 4
Z9 5
U1 0
U2 1
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 JUN
PY 2010
VL 8
IS 6
BP 885
EP 895
DI 10.1158/1541-7786.MCR-09-0467
PG 11
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 611TH
UT WOS:000278845400008
PM 20530579
ER
PT J
AU Chae, SY
Kim, TH
Park, K
Jin, CH
Son, S
Lee, S
Youn, YS
Kim, K
Jo, DG
Kwon, IC
Chen, XY
Lee, KC
AF Chae, Su Young
Kim, Tae Hyung
Park, Kyeongsoon
Jin, Cheng-Hao
Son, Sohee
Lee, Seulki
Youn, Yu Seok
Kim, Kwangmeyung
Jo, Dong-Gyu
Kwon, Ick Chan
Chen, Xiaoyuan
Lee, Kang Choon
TI Improved Antitumor Activity and Tumor Targeting of NH2-Terminal-Specific
PEGylated Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID SITE-SPECIFIC PEGYLATION; TUMORICIDAL ACTIVITY; RECEPTOR AGONISTS;
CANCER-CELLS; TNF-ALPHA; IN-VIVO; TRAIL; DEATH; DELIVERY;
PHARMACOKINETICS
AB Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered an attractive anticancer agent due to its tumor cell-specific cytotoxicity. However, its low stability, solubility, unexpected side effects, and weak pharmacokinetic profiles restrict its successful clinical application. To develop efficient TRAIL-based anticancer biotherapeutics, a new version of trimeric TRAIL was constructed by incorporating trimer-forming zipper sequences (HZ-TRAIL), and then NH2-terminal-specific PEGylation was done to produce PEGylated TRAIL (PEG-HZ-TRAIL). The biological, physicochemical, and pharmaceutical characteristics of PEG-HZ-TRAIL were then investigated using various in vitro and in vivo experiments, including a cell-based cytotoxicity test, a solubility test, pharmacokinetic analysis, and antitumor efficacy evaluations. Although slight activity loss occurred after PEGylation, PEG-HZ-TRAIL showed excellent tumor cell-specific cytotoxic effects via apoptotic pathways with negligible normal cell toxicity. The stability and pharmacokinetic problems of HZ-TRAIL were successfully overcome by PEGylation. Furthermore, in vivo antitumor tests revealed that PEG-HZ-TRAIL treatment enhanced therapeutic potentials compared with HZ-TRAIL in tumor xenograft animal models, and these enhancements were attributed to its better pharmacokinetic properties and tumor-targeting performance. These findings show that PEG-HZ-TRAIL administration provides an effective antitumor treatment, which exhibits superior tumor targeting and better inhibits tumor growth, and suggest that PEG-HZ-TRAIL should be considered a potential candidate for antitumor biotherapy. Mol Cancer Ther; 9(6); 1719-29. (C)2010 AACR.
C1 [Lee, Kang Choon] Sungkyunkwan Univ, Drug Targeting Lab, Coll Pharm, Suwon 440746, South Korea.
[Park, Kyeongsoon; Kim, Kwangmeyung; Kwon, Ick Chan] Korea Inst Sci & Technol, Biomed Res Ctr, Seoul, South Korea.
[Lee, Seulki; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA.
[Youn, Yu Seok] Pusan Natl Univ, Coll Pharm, Pusan, South Korea.
RP Lee, KC (reprint author), Sungkyunkwan Univ, Drug Targeting Lab, Coll Pharm, 300 Chonchon Dong, Suwon 440746, South Korea.
EM kclee@skku.edu
FU Korean Ministry of Education, Science and Technology, Korea
FX Grant Support; Korean Ministry of Education, Science and Technology,
Korea.
NR 41
TC 38
Z9 38
U1 0
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD JUN
PY 2010
VL 9
IS 6
BP 1719
EP 1729
DI 10.1158/1535-7163.MCT-09-1076
PG 11
WC Oncology
SC Oncology
GA 608FS
UT WOS:000278569200024
PM 20515949
ER
PT J
AU Tailor, TD
Hanna, G
Yarmolenko, PS
Dreher, MR
Betof, AS
Nixon, AB
Spasojevic, I
Dewhirst, MW
AF Tailor, Tina D.
Hanna, Gabi
Yarmolenko, Pavel S.
Dreher, Matthew R.
Betof, Allison S.
Nixon, Andrew B.
Spasojevic, Ivan
Dewhirst, Mark W.
TI Effect of Pazopanib on Tumor Microenvironment and Liposome Delivery
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID INTERSTITIAL FLUID PRESSURE; ENDOTHELIAL GROWTH-FACTOR; CELL
LUNG-CANCER; MULTIKINASE ANGIOGENESIS INHIBITOR; VASCULAR-PERMEABILITY;
DRUG-DELIVERY; ANTIANGIOGENIC THERAPY; BLOOD-VESSELS; PDGFR-BETA;
NORMALIZATION
AB Pathologic angiogenesis creates an abnormal microenvironment in solid tumors, characterized by elevated interstitial fluid pressure (IFP) and hypoxia. Emerging theories suggest that judicious downregulation of proangiogenic signaling pathways may transiently "normalize" the vascular bed, making it more suitable for drug delivery and radiotherapy. In this work, we investigate the role of pazopanib, a small-molecule inhibitor of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptors, on tumor IFP, angiogenesis, hypoxia, and liposomal drug delivery. Nude mice bearing A549 human non-small cell lung cancer xenografts were treated with 100 mg/kg pazopanib (n = 20) or vehicle (n = 20) through oral gavage for 8 days, followed by a one-time intravenous dose of 10 mg/kg Doxil (liposomal doxorubicin). Pazopanib treatment resulted in significant reduction of tumor IFP and decreased vessel density, assessed by CD31 staining. Despite these trends toward normalization, high-performance liquid chromatography revealed no differences in doxorubicin concentration between pazopanib-treated and control tumors, with Doxil penetration from microvessels being significantly reduced in the pazopanib group. Additionally, tumor hypoxia, evaluated by CA-IX immunostaining and confirmed in a second study by EF5 expression (n = 4, 100 mg/kg pazopanib; n = 4, vehicle), was increased in pazopanib-treated tumors. Our results suggest that the classic definition of tumor "normalization" may undermine the crucial role of vessel permeability and oncotic pressure gradients in liposomal drug delivery, and that functional measures of normalization, such as reduced IFP and hypoxia, may not occur in parallel temporal windows. Mol Cancer Ther; 9(6); 1798-808. (C)2010 AACR.
C1 [Hanna, Gabi; Betof, Allison S.; Dewhirst, Mark W.] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27710 USA.
[Tailor, Tina D.] Duke Univ, Sch Med, Chevy Chase, MD USA.
[Tailor, Tina D.] Howard Hughes Med Inst, Chevy Chase, MD USA.
[Betof, Allison S.; Dewhirst, Mark W.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA.
[Yarmolenko, Pavel S.; Dewhirst, Mark W.] Duke Univ, Med Ctr, Dept Biomed Engn, Durham, NC 27710 USA.
[Nixon, Andrew B.; Spasojevic, Ivan] Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Durham, NC 27710 USA.
[Yarmolenko, Pavel S.; Dreher, Matthew R.] NIH, Radiol & Imaging Sci Clin Ctr, Bethesda, MD 20892 USA.
RP Dewhirst, MW (reprint author), Duke Univ, Med Ctr, Dept Radiat Oncol, Box 3455,201 MSRB,Res Dr, Durham, NC 27710 USA.
EM dewhirst@radonc.duke.edu
FU GlaxoSmithKline; Duke Cancer Center; Howard Hughes Medical Institute
FX Research contract from GlaxoSmithKline and support from Duke Cancer
Center and Howard Hughes Medical Institute.
NR 50
TC 54
Z9 55
U1 3
U2 20
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD JUN
PY 2010
VL 9
IS 6
BP 1798
EP 1808
DI 10.1158/1535-7163.MCT-09-0856
PG 11
WC Oncology
SC Oncology
GA 608FS
UT WOS:000278569200031
PM 20515941
ER
PT J
AU Seki, N
Toh, U
Sayers, TJ
Fujii, T
Miyagi, M
Akagi, Y
Kusukawa, J
Kage, M
Shirouzu, K
Yamana, H
AF Seki, Naoko
Toh, Uhi
Sayers, Thomas J.
Fujii, Teruhiko
Miyagi, Motoshi
Akagi, Yoshito
Kusukawa, Jingo
Kage, Masayoshi
Shirouzu, Kazuo
Yamana, Hideaki
TI Bortezomib Sensitizes Human Esophageal Squamous Cell Carcinoma Cells to
TRAIL-Mediated Apoptosis via Activation of Both Extrinsic and Intrinsic
Apoptosis Pathways
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID PROTEASOME INHIBITOR BORTEZOMIB; HUMAN CANCER-CELLS; UP-REGULATION;
LIGAND TRAIL; TNF-FAMILY; C-FLIP; RECEPTOR; DEATH; RESISTANCE; INDUCTION
AB Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive human cancers, and novel treatment modalities are required. We investigated the therapeutic potential of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) in combination with the proteasome inhibitor bortezomib (Velcade) on human ESCC cell lines. Bortezomib enhanced the susceptibility to TRAIL in 12 of the 15 ESCC cell lines tested, although most showed low sensitivity to TRAIL as a single agent. The enhancement of TRAIL-induced apoptosis by bortezomib was caspase dependent. Increased processing of caspase-8 often accompanied enhancement of TRAIL-induced apoptosis by bortezomib. However, the increased cell surface expression of death receptors observed on bortezomib treatment did not seem to be crucial for this effect. For some ESCC, bortezomib treatment resulted in a more efficient recruitment of caspase-8 and the Fas-associated death domain to the death-inducing signaling complex. Additional downregulation of the cellular FLICE-inhibitory protein long isoform [c-FLIP(L)] could cooperate in the activation of the extrinsic pathway in some cases. For other ESCC, the crucial effect of bortezomib treatment seemed to be increased signaling via the intrinsic apoptotic pathway on subsequent exposure to TRAIL. Thus, bortezomib could sensitize ESCC to TRAIL apoptosis by multiple molecular mechanisms of action. Therefore, the combination of bortezomib and TRAIL might be a novel therapeutic strategy for ESCC patients who fail to respond to standard chemoradiotherapy that predominantly targets the mitochondrial apoptotic pathway. Mol Cancer Ther; 9(6); 1842-51. (C)2010 AACR.
C1 [Seki, Naoko; Toh, Uhi; Fujii, Teruhiko; Kage, Masayoshi; Yamana, Hideaki] Kurume Univ, Res Ctr Innovat Canc Therapy, Kurume, Fukuoka 8300011, Japan.
[Toh, Uhi; Fujii, Teruhiko; Miyagi, Motoshi; Akagi, Yoshito; Shirouzu, Kazuo; Yamana, Hideaki] Kurume Univ, Dept Surg, Sch Med, Kurume, Fukuoka 8300011, Japan.
[Kusukawa, Jingo] Kurume Univ Hosp, Dent & Oral Med Ctr, Kurume, Fukuoka, Japan.
[Kage, Masayoshi] Kurume Univ Hosp, Dept Pathol, Kurume, Fukuoka, Japan.
[Fujii, Teruhiko] Natl Hosp Org Kyushu Med Ctr, Fukuoka, Japan.
[Sayers, Thomas J.] NCI, Expt Immunol Lab, Canc & Inflammat Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21701 USA.
RP Seki, N (reprint author), Kurume Univ, Res Ctr Innovat Canc Therapy, 67 Asahi Machi, Kurume, Fukuoka 8300011, Japan.
EM seki_naoko@kurume-u.ac.jp
RI Sayers, Thomas/G-4859-2015
FU Japan Society for the Promotion of Science; Ministry of Education,
Culture, Sports, Science and Technology; National Cancer Institute, NIH
[N01-CO-12400]; Center for Cancer Research, National Cancer Institute,
NIH
FX Grant-in-Aid for Scientific Research from Japan Society for the
Promotion of Science and "High-Tech Research Center" Project for Private
Universities: matching fund subsidy from Ministry of Education, Culture,
Sports, Science and Technology. This project has been funded in whole or
in part with federal funds from the National Cancer Institute, NIH,
under contract N01-CO-12400. This research was supported (in part) by
the Intramural Research Program of the Center for Cancer Research,
National Cancer Institute, NIH.
NR 50
TC 23
Z9 25
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD JUN
PY 2010
VL 9
IS 6
BP 1842
EP 1851
DI 10.1158/1535-7163.MCT-09-0918
PG 10
WC Oncology
SC Oncology
GA 608FS
UT WOS:000278569200035
PM 20515944
ER
PT J
AU Holbeck, S
Chang, JJ
Best, AM
Bookout, AL
Mangelsdorf, DJ
Martinez, ED
AF Holbeck, Susan
Chang, Jianjun
Best, Anne M.
Bookout, Angie L.
Mangelsdorf, David J.
Martinez, Elisabeth D.
TI Expression Profiling of Nuclear Receptors in the NCI60 Cancer Cell Panel
Reveals Receptor-Drug and Receptor-Gene Interactions
SO MOLECULAR ENDOCRINOLOGY
LA English
DT Article
ID HUMAN BREAST-CANCER; NEURAL STEM-CELLS; RETINOIC ACID; TUMOR-SUPPRESSOR;
PPAR-GAMMA; FACTOR-I; MILTEFOSINE; LINES; BETA; PHOSPHOLIPIDS
AB We profiled the expression of the 48 human nuclear receptors (NRs) by quantitative RT-PCR in 51 human cancer cell lines of the NCI60 collection derived from nine different tissues. NR mRNA expression accurately classified melanoma, colon, and renal cancers, whereas lung, breast, prostate, central nervous system, and leukemia cell lines exhibited heterogeneous receptor expression. Importantly, receptor mRNA levels faithfully predicted the growth-inhibitory qualities of receptor ligands in nonendocrine tumors. Correlation analysis using NR expression profiles and drug response information across the cell line panel uncovered a number of new potential receptor-drug interactions, suggesting that in these cases, individual receptor levels may predict response to chemotherapeutic interventions. Similarly, by cross-comparing receptor levels within our expression dataset and relating these profiles to existing microarray gene expression data, we defined interactions among receptors and between receptors and other genes that can now be mechanistically queried. This work supports the strategy of using NR expression profiling to classify various types of cancer, define NR-drug interactions and receptor-gene networks, predict cancer-drug sensitivity, and identify druggable targets that may be pharmacologically manipulated for potential therapeutic intervention. (Molecular Endocrinology 24: 1287-1296, 2010)
C1 [Chang, Jianjun; Best, Anne M.; Martinez, Elisabeth D.] Univ Texas SW Med Ctr Dallas, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA.
[Mangelsdorf, David J.] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA.
[Bookout, Angie L.; Mangelsdorf, David J.; Martinez, Elisabeth D.] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA.
[Holbeck, Susan] NCI, NIH, Rockville, MD 20852 USA.
RP Martinez, ED (reprint author), Univ Texas SW Med Ctr Dallas, Hamon Ctr Therapeut Oncol Res, 6000 Harry Hines Blvd, Dallas, TX 75390 USA.
EM elisabeth.martinez@utsouthwestern.edu
FU Nuclear Receptor Signaling Atlas [U19DK062434]; Howard Hughes Medical
Institute; Robert A. Welch Foundation [I-275]; Doctors Cancer
Foundation; National Cancer Institute [5K22CA118717]
FX This work was supported by the Nuclear Receptor Signaling Atlas
(U19DK062434 to D.J.M.), Howard Hughes Medical Institute (to D.J.M.),
the Robert A. Welch Foundation (grant I-275 to D.J.M.), the Doctors
Cancer Foundation (to E. M.), and the National Cancer Institute
(5K22CA118717 to E. M.).
NR 48
TC 35
Z9 36
U1 0
U2 2
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0888-8809
J9 MOL ENDOCRINOL
JI Mol. Endocrinol.
PD JUN
PY 2010
VL 24
IS 6
BP 1287
EP 1296
DI 10.1210/me.2010-0040
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 601EB
UT WOS:000278039900015
PM 20375240
ER
PT J
AU Huizing, M
Dorward, H
Ly, L
Klootwijk, E
Kleta, R
Skovby, F
Pei, WH
Feldman, B
Gahl, WA
Anikster, Y
AF Huizing, Marjan
Dorward, Heidi
Ly, Lien
Klootwijk, Enriko
Kleta, Robert
Skovby, Flemming
Pei, Wuhong
Feldman, Benjamin
Gahl, William A.
Anikster, Yair
TI OPA3, mutated in 3-methylglutaconic aciduria type III, encodes two
transcripts targeted primarily to mitochondria
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE Optic atrophy; OPA3; 3-Methylglutaconic acid; Mitochondrion; Peroxisome;
Green fluorescent protein; Sorting signal
ID OPTIC ATROPHY PLUS; GENOME EVOLUTION; COSTEFF-SYNDROME; BARTH-SYNDROME;
GENE; TRIPEPTIDE; DISORDERS; MEMBRANE; PROTEINS; DISEASE
AB 3-Methylglutaconic aciduria type Ill (3-MGCA type III), caused by recessive mutations in the 2-exon gene OPA3, is characterized by early-onset bilateral optic atrophy, later-onset extrapyramidal dysfunction, and increased urinary excretion of 3-methylglutaconic acid and 3-methylglutaric acid. Here we report the identification of a novel third OPA3 coding exon, the apparent product of a segmental duplication event, resulting in two gene transcripts, OPA3A and OPA3B. OPA3A deficiency (as in optic atrophy type 3) causes up-regulation of OPA3B. OPA3 protein function remains unknown, but it contains a putative mitochondrial leader sequence, mitochondrial sorting signal and a peroxisomal sorting signal. Our green fluorescent protein tagged OPA3 expression studies found its localization to be predominantly mitochondrial. These findings thus place the cellular metabolic defect of 3-MGCA type III in the mitochondrion rather than the peroxisome and implicate loss of OPA3A rather than gain of OPA3B in disease etiology. Published by Elsevier Inc.
C1 [Huizing, Marjan; Dorward, Heidi; Ly, Lien; Klootwijk, Enriko; Pei, Wuhong; Feldman, Benjamin; Gahl, William A.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Klootwijk, Enriko; Kleta, Robert] UCL, Ctr Nephrol, London WC1E 6BT, England.
[Skovby, Flemming] Copenhagen Univ Hosp, Dept Clin Genet, Copenhagen, Denmark.
[Anikster, Yair] Tel Aviv Univ, Sackler Sch Med, Chaim Sheba Med Ctr, Safra Childrens Hosp,Metab Dis Unit, Tel Hashomer, Israel.
RP Huizing, M (reprint author), NHGRI, Med Genet Branch, NIH, 10 Ctr Dr,MSC 1851,Bld 10,Rm 10C103, Bethesda, MD 20892 USA.
EM mhuizing@mail.nih.gov
OI Feldman, Benjamin/0000-0003-4838-8641
FU National Human Genome Research Institute, National Institutes of Health,
Bethesda, MD, USA; Costeff Support Group Foundation
FX We thank Ian Nouvel for skillful laboratory assistance. This study was
supported by the Intramural Research Program of the National Human
Genome Research Institute, National Institutes of Health, Bethesda, MD,
USA and by the Costeff Support Group Foundation (Y.A.).
NR 35
TC 16
Z9 16
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 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD JUN
PY 2010
VL 100
IS 2
BP 149
EP 154
DI 10.1016/j.ymgme.2010.03.005
PG 6
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 601SP
UT WOS:000278084600008
PM 20350831
ER
PT J
AU Baio, G
Fabbi, M
Salvi, S
de Totero, D
Truini, M
Ferrini, S
Neumaier, CE
AF Baio, Gabriella
Fabbi, Marina
Salvi, Sandra
de Totero, Daniela
Truini, Mauro
Ferrini, Silvano
Neumaier, Carlo Emanuele
TI Two-Step In Vivo Tumor Targeting by Biotin-Conjugated Antibodies and
Superparamagnetic Nanoparticles Assessed by Magnetic Resonance Imaging
at 1.5 T
SO MOLECULAR IMAGING AND BIOLOGY
LA English
DT Article
DE Magnetic resonance imaging; Iron oxide particles; In vivo small animal
MRI; Targeted contrast agent; Antibody
ID IRON-OXIDE; RAT-BRAIN; CELLS; CONTRAST; MR; EXPRESSION; TRACKING; AGENT;
MODEL; VITRO
AB The purpose of this study was to assess two-step in vivo tumor targeting by specific biotin-conjugated antibodies and ultrasmall superparamagnetic iron oxide (USPIO)-anti-biotin nanoparticles as contrast agents for magnetic resonance imaging (MRI) at 1.5 T.
D430B human lymphoma cells, expressing the CD70 surface antigen, were injected either s.c. or i.v. to induce pseudo-metastases in NOD/SCID mice. Thirty micrograms of biotin-conjugated monoclonal anti-CD70 was injected i.v., followed 4 h later by 8 A mu mol Fe/Kg USPIO-anti-biotin. After 24 h, MRI was performed on T2* and b-FFE sequences. Signal intensity (SI) was calculated before and after USPIO-anti-biotin administration.
Subcutaneous xenografts showed a dishomogeneous 30% decrease in SI on T2* with anti-CD70 + USPIO-anti-biotin treatment. Pseudo-metastatic xenografts showed a slight reduction in SI on T2*, but a 60% decrease in SI on b-FFE-weighted sequences. Prussian blue staining confirmed the presence of iron nanoparticles in the excised tumors.
MRI at 1.5 T can detect tumors by a two-step in vivo biotin-based protocol, which may allow the targeting of any cell surface antigen.
C1 [Baio, Gabriella; Neumaier, Carlo Emanuele] Natl Canc Inst, Dept Diagnost Imaging, IST, I-16132 Genoa, Italy.
[Fabbi, Marina; de Totero, Daniela; Ferrini, Silvano] Natl Canc Inst, Unit Immunol Therapy, IST, I-16132 Genoa, Italy.
[Salvi, Sandra; Truini, Mauro] Natl Canc Inst, Dept Pathol, IST, I-16132 Genoa, Italy.
RP Neumaier, CE (reprint author), Natl Canc Inst, Dept Diagnost Imaging, IST, Largo Rosanna Benzi 10, I-16132 Genoa, Italy.
EM carlo.neumaier@istge.it
RI Fabbi, Marina/I-1290-2012; Baio, Gabriella/M-7621-2015;
OI Baio, Gabriella/0000-0002-8397-5318; Ferrini,
Silvano/0000-0001-7254-2616
FU Italian Association for Cancer Research; Regione Liguria; Italian
Ministry of Health
FX This work was supported by the Italian Association for Cancer Research
(AIRC), the Regione Liguria, and the Italian Ministry of Health. We
thank Mr. T. Wiley for language revision.
NR 26
TC 15
Z9 19
U1 1
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1536-1632
J9 MOL IMAGING BIOL
JI Mol. Imaging. Biol.
PD JUN
PY 2010
VL 12
IS 3
BP 305
EP 315
DI 10.1007/s11307-009-0264-6
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 592JO
UT WOS:000277375300009
PM 19806404
ER
PT J
AU Zhang, D
Hu, XM
Qian, L
O'Callaghan, JP
Hong, JS
AF Zhang, Dan
Hu, Xiaoming
Qian, Li
O'Callaghan, James P.
Hong, Jau-Shyong
TI Astrogliosis in CNS Pathologies: Is There A Role for Microglia?
SO MOLECULAR NEUROBIOLOGY
LA English
DT Article
DE Astrocyte; GFAP; Astrogliosis; Microglia; Cytokine
ID FIBRILLARY ACIDIC PROTEIN; TUMOR-NECROSIS-FACTOR; SPINAL-CORD-INJURY;
CENTRAL-NERVOUS-SYSTEM; NITRIC-OXIDE SYNTHASE; BLOOD-BRAIN-BARRIER;
PROGRAMMED CELL-DEATH; FACTOR-ALPHA; REACTIVE ASTROGLIOSIS; NEUROTROPHIC
FACTOR
AB Astrogliosis, a cellular reaction with specific structural and functional characteristics, represents a remarkably homotypic response of astrocytes to all kinds of central nervous system (CNS) pathologies. Astrocytes play diverse functions in the brain, both harmful and beneficial. Mounting evidence indicates that astrogliosis is an underlying component of a diverse range of diseases and associated neuropathologies. The mechanisms that lead to astrogliosis are not fully understood, nevertheless, damaged neurons have long been reported to induce astrogliosis and astrogliosis has been used as an index for underlying neuronal damage. As the predominant source of proinflammatory factors in the CNS, microglia are readily activated under certain pathological conditions. An increasing body of evidence suggests that release of cytokines and other soluble products by activated microglia can significantly influence the subsequent development of astrogliosis and scar formation in CNS. It is well known that damaged neurons activate microglia very quickly, therefore, it is possible that activated microglia contribute factors/mediators through which damaged neuron induce astrogliosis. The hypothesis that activated microglia initiate and maintain astrogliosis suggests that suppression of microglial overactivation might effectively attenuate reactive astrogliosis. Development of targeted anti-microglial activation therapies might slow or halt the progression of astrogliosis and, therefore, help achieve a more beneficial environment in various CNS pathologies.
C1 [Zhang, Dan; Hu, Xiaoming; Qian, Li; Hong, Jau-Shyong] Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA.
[Hu, Xiaoming] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA.
[Hu, Xiaoming] Univ Pittsburgh, Sch Med, Pittsburgh Inst Neurodegenerat Dis, Pittsburgh, PA 15261 USA.
[Qian, Li] Univ N Carolina, Comprehens Ctr Inflammatory Disorders, Chapel Hill, NC 27599 USA.
[O'Callaghan, James P.] Ctr Dis Control & Prevent, NIOSH, Morgantown, WV 26505 USA.
RP Zhang, D (reprint author), Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA.
EM zhangd2@niehs.nih.gov
RI O'Callaghan, James/O-2958-2013
FU Intramural NIH HHS [ZIA ES090082-13, Z01 ES090082-12]
NR 109
TC 116
Z9 122
U1 2
U2 14
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0893-7648
J9 MOL NEUROBIOL
JI Mol. Neurobiol.
PD JUN
PY 2010
VL 41
IS 2-3
SI SI
BP 232
EP 241
DI 10.1007/s12035-010-8098-4
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 601WI
UT WOS:000278095800018
PM 20148316
ER
PT J
AU Mavaddat, N
Antoniou, AC
Easton, DF
Garcia-Closas, M
AF Mavaddat, Nasim
Antoniou, Antonis C.
Easton, Douglas F.
Garcia-Closas, Montserrat
TI Genetic susceptibility to breast cancer
SO MOLECULAR ONCOLOGY
LA English
DT Review
DE Breast cancer; Genetic susceptibility; Aetiology of breast cancer;
BRCA1/2 mutation carriers; Pathology
ID BRCA2 MUTATION CARRIERS; GENOME-WIDE ASSOCIATION; PROGESTERONE-RECEPTOR
STATUS; KERATINOCYTE GROWTH-FACTOR; BILATERAL PROPHYLACTIC MASTECTOMY;
AFRICAN-AMERICAN WOMEN; REDUCING SALPINGO-OOPHORECTOMY; DEL PROMOTER
POLYMORPHISM; ESTROGEN-RECEPTOR; FAMILIAL BREAST
AB Genetic and lifestyle/environmental factors are implicated in the aetiology of breast cancer. This review summarizes the current state of knowledge on rare high penetrance mutations, as well as moderate and low-penetrance genetic variants implicated in breast cancer aetiology. We summarize recent discoveries from large collaborative efforts to combine data from candidate gene studies, and to conduct genome-wide association studies (GWAS), primarily in breast cancers in the general population. These findings are compared with results from collaborative efforts aiming to identify genetic modifiers in BRCA1 and BRCA2 carriers. Breast cancer is a heterogeneous disease, and tumours from BRCA1 and BRCA2 carriers display distinct pathological characteristics when compared with tumours unselected for family history. The relationship between genetic variants and pathological subtypes of breast cancer, and the implication of discoveries of novel genetic variants to risk prediction in BRCA1/2 mutation carriers and in populations unselected for mutation carrier status, are discussed. (C) 2010 Published by Elsevier B.V. on behalf of Federation of European Biochemical Societies.
C1 [Garcia-Closas, Montserrat] Univ Cambridge, Dept Oncol, Strangeways Res Lab, Cambridge CB1 8RN, England.
[Mavaddat, Nasim; Antoniou, Antonis C.; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England.
[Garcia-Closas, Montserrat] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
RP Garcia-Closas, M (reprint author), Univ Cambridge, Dept Oncol, Strangeways Res Lab, Worts Causeway, Cambridge CB1 8RN, England.
EM Montse.GarciaClosas@icr.ac.uk
RI Garcia-Closas, Montserrat /F-3871-2015
OI Garcia-Closas, Montserrat /0000-0003-1033-2650
FU Cancer Research UK [11174, 10118]
NR 172
TC 138
Z9 140
U1 2
U2 23
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1574-7891
J9 MOL ONCOL
JI Mol. Oncol.
PD JUN
PY 2010
VL 4
IS 3
BP 174
EP 191
DI 10.1016/j.molonc.2010.04.011
PG 18
WC Oncology
SC Oncology
GA 627NI
UT WOS:000280046100002
PM 20542480
ER
PT J
AU Lee, HJ
Rao, JS
Chang, L
Rapoport, SI
Kim, HW
AF Lee, H-J
Rao, J. S.
Chang, L.
Rapoport, S. I.
Kim, H-W
TI Chronic imipramine but not bupropion increases arachidonic acid
signaling in rat brain: is this related to 'switching' in bipolar
disorder?
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE arachidonic acid; bipolar disorder; bupropion; cPLA(2); imipramine;
switching
ID CYTOSOLIC PHOSPHOLIPASE A(2); RECEPTOR AGONIST (+)BW373U86;
MESSENGER-RNA EXPRESSION; FORCED SWIM TEST; UNANESTHETIZED RAT;
FRONTAL-CORTEX; FATTY-ACID; DOCOSAHEXAENOIC ACID; CHRONIC LITHIUM; MOOD
STABILIZERS
AB Agents effective against mania in bipolar disorder are reported to decrease turnover of arachidonic acid (AA) in phospholipids and expression of calcium-dependent AA-selective cytosolic phospholipase A(2) (cPLA(2)) in rat brain. In contrast, fluoxetine, an antidepressant that is reported to switch bipolar depressed patients to mania, increases cPLA(2) expression and AA turnover in rat brain. We therefore hypothesized that antidepressants that increase switching to mania generally increase cPLA(2) and AA turnover in brain. To test this hypothesis, adult male CDF-344 rats were administered imipramine and bupropion, with reported high and low switching rates, respectively, at daily doses of 10 and 30 mg kg(-1) i.p., respectively, or i.p. saline (control) for 21 days. Frontal cortex expression of different PLA(2) enzymes and AA turnover rates in brain when the rats were unanesthetized were measured. Compared with chronic saline, chronic imipramine but not bupropion significantly increased cortex cPLA(2) mRNA activity, protein and phosphorylation, expression of the cPLA(2) transcription factor, activator protein-2 alpha (AP-2 alpha) and AA turnover in phospholipids. Protein levels of secretory phospholipase A(2), calcium-independent phospholipase A(2), cyclooxygenase ( COX)-1 and COX-2 were unchanged, and prostaglandin E(2) was unaffected. These results, taken with prior data on chronic fluoxetine in rats, suggest that antidepressants that increase the switching tendency of bipolar depressed patients to mania do so by increasing AA recycling and metabolism in brain. Mania in bipolar disorder thus may involve upregulated brain AA metabolism. Molecular Psychiatry (2010) 15, 602-614; doi: 10.1038/mp.2008.117; published online 4 November 2008
C1 [Lee, H-J; Rao, J. S.; Chang, L.; Rapoport, S. I.; Kim, H-W] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
RP Kim, HW (reprint author), NIA, Brain Physiol & Metab Sect, NIH, 9000 Rockville Pike,Bldg 9,1S-126, Bethesda, MD 20892 USA.
EM kimhyung@mail.nih.gov
FU National Institute on Aging, National Institutes of Health
FX This work was entirely supported by the Intramural Research Program of
the National Institute on Aging, National Institutes of Health.
NR 91
TC 19
Z9 20
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD JUN
PY 2010
VL 15
IS 6
BP 602
EP 614
DI 10.1038/mp.2008.117
PG 13
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 599DZ
UT WOS:000277891800004
PM 18982003
ER
PT J
AU Terracciano, A
Sanna, S
Uda, M
Deiana, B
Usala, G
Busonero, F
Maschio, A
Scally, M
Patriciu, N
Chen, WM
Distel, MA
Slagboom, EP
Boomsma, DI
Villafuerte, S
Sliwerska, E
Burmeister, M
Amin, N
Janssens, ACJW
van Duijn, CM
Schlessinger, D
Abecasis, GR
Costa, PT
AF Terracciano, A.
Sanna, S.
Uda, M.
Deiana, B.
Usala, G.
Busonero, F.
Maschio, A.
Scally, M.
Patriciu, N.
Chen, W-M
Distel, M. A.
Slagboom, E. P.
Boomsma, D. I.
Villafuerte, S.
Sliwerska, E.
Burmeister, M.
Amin, N.
Janssens, A. C. J. W.
van Duijn, C. M.
Schlessinger, D.
Abecasis, G. R.
Costa, P. T., Jr.
TI Genome-wide association scan for five major dimensions of personality
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE personality; genome-wide association; founder population; psychiatry;
five-factor model
ID POPULATION-BASED TWIN; DEFICIT HYPERACTIVITY DISORDER;
NATIONAL-COMORBIDITY-SURVEY; CORONARY-ARTERY-DISEASE; CROSS-CULTURAL
TWIN; NEO-PI-R; CLOCK GENE; ALZHEIMER-DISEASE; LINKAGE ANALYSIS; 3111T/C
POLYMORPHISM
AB Personality traits are summarized by five broad dimensions with pervasive influences on major life outcomes, strong links to psychiatric disorders and clear heritable components. To identify genetic variants associated with each of the five dimensions of personality we performed a genome-wide association (GWA) scan of 3972 individuals from a genetically isolated population within Sardinia, Italy. On the basis of the analyses of 362 129 single-nucleotide polymorphisms we found several strong signals within or near genes previously implicated in psychiatric disorders. They include the association of neuroticism with SNAP25 (rs362584, P= 5 x 10(-5)), extraversion with BDNF and two cadherin genes (CDH13 and CDH23; Ps<5 x 10(-5)), openness with CNTNAP2 (rs10251794, P= 3 x 10(-5)), agreeableness with CLOCK (rs6832769, P= 9 x 10(-6)) and conscientiousness with DYRK1A (rs2835731, P= 3 x 10(-5)). Effect sizes were small (less than 1% of variance), and most failed to replicate in the follow-up independent samples (N up to 3903), though the association between agreeableness and CLOCK was supported in two of three replication samples (overall P= 2 x 10(-5)). We infer that a large number of loci may influence personality traits and disorders, requiring larger sample sizes for the GWA approach to confidently identify associated genetic variants. Molecular Psychiatry (2010) 15, 647-656; doi: 10.1038/mp.2008.113; published online 28 October 2008
C1 [Terracciano, A.] NIA, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA.
[Sanna, S.; Uda, M.; Deiana, B.; Usala, G.; Busonero, F.; Maschio, A.] CNR, Ist Neurogenet & Neurofarmacol, Cagliari, Italy.
[Chen, W-M] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
[Distel, M. A.; Boomsma, D. I.] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.
[Slagboom, E. P.] Leiden Univ, Med Ctr, Mol Epidemiol Sect, Leiden, Netherlands.
[Villafuerte, S.; Sliwerska, E.; Burmeister, M.] Univ Michigan, Mol & Behav Neurosci Inst, Ann Arbor, MI 48109 USA.
[Villafuerte, S.; Burmeister, M.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA.
[Burmeister, M.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
[Amin, N.; Janssens, A. C. J. W.; van Duijn, C. M.] Erasmus Univ, Dept Epidemiol & Biostat, Med Ctr, NL-3000 DR Rotterdam, Netherlands.
[Amin, N.; van Duijn, C. M.] Erasmus Univ, Dept Clin Genet, Med Ctr, NL-3000 DR Rotterdam, Netherlands.
[Abecasis, G. R.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
RP Terracciano, A (reprint author), NIA, Biomed Res Ctr, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM terraccianoa@mail.nih.gov
RI terracciano, antonio/B-1884-2008; Abecasis, Goncalo/B-7840-2010;
Burmeister, Margit/A-3157-2013; Slagboom, P. Eline/R-4790-2016;
OI Burmeister, Margit/0000-0002-1914-2434; Slagboom, P.
Eline/0000-0002-2875-4723; sanna, serena/0000-0002-3768-1749; Abecasis,
Goncalo/0000-0003-1509-1825; Costa, Paul/0000-0003-4375-1712; Janssens,
A Cecile/0000-0002-6153-4976
FU NIH, National Institute on Aging; National Institute of Health NIH-NIMH
[R21 MH070793]; National Alliance for Research on Schizophrenia and
Depression (NARSAD); Independent Investigator Award; Young Investigator
Award
FX We thank the individuals who participated in this study; the SardiNIA
team thanks Monsignore Piseddu (Bishop of Ogliastra), the mayors of the
four Sardinian towns (Lanusei, Ilbono, Arzana and Elini), and the head
of the Public Health Unit ASL4 for cooperation. We thank Professor
Antonio Cao for his leadership of the SardiNIA project. This research
was supported by the Intramural Research Program of the NIH, National
Institute on Aging. Dr Margit Burmeister's laboratory was supported by
the National Institute of Health NIH-NIMH R21 MH070793 and the National
Alliance for Research on Schizophrenia and Depression (NARSAD),
Independent Investigator Award (MB) and Young Investigator Award (SV).
NR 95
TC 58
Z9 60
U1 2
U2 23
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD JUN
PY 2010
VL 15
IS 6
BP 647
EP 656
DI 10.1038/mp.2008.113
PG 10
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 599DZ
UT WOS:000277891800008
ER
PT J
AU Yiu, WH
Lee, YM
Peng, WT
Pan, CJ
Mead, PA
Mansfield, BC
Chou, JY
AF Yiu, Wai Han
Lee, Young Mok
Peng, Wen-Tao
Pan, Chi-Jiunn
Mead, Paul A.
Mansfield, Brian C.
Chou, Janice Y.
TI Complete Normalization of Hepatic G6PC Deficiency in Murine Glycogen
Storage Disease Type Ia Using Gene Therapy
SO MOLECULAR THERAPY
LA English
DT Article
ID ADENOASSOCIATED VIRUS VECTORS; LIVER TRANSDUCTION;
GLUCOSE-6-PHOSPHATASE; PROMOTER; MOUSE; CYTOMEGALOVIRUS; MANAGEMENT;
DELIVERY; GENOMES; MICE
AB Glycogen storage disease type Ia (GSD-Ia) patients deficient in glucose-6-phosphatase-alpha (G6Pase-alpha or G6PC) manifest disturbed glucose homeostasis. We examined the efficacy of liver G6Pase-alpha delivery mediated by AAV-GPE, an adeno-associated virus (AAV) serotype 8 vector expressing human G6Pase-alpha directed by the human G6PC promoter/enhancer (GPE), and compared it to AAV-CBA, that directed murine G6Pase-alpha expression using a hybrid chicken beta-actin (CBA) promoter/cytomegalovirus (CMV) enhancer. The AAV-GPE directed hepatic G6Pase-alpha expression in the infused G6pc(-/-) mice declined 12-fold from age 2 to 6 weeks but stabilized at wild-type levels from age 6 to 24 weeks. In contrast, the expression directed by AAV-CBA declined 95-fold over 24 weeks, demonstrating that the GPE is more effective in directing persistent in vivo hepatic transgene expression. We further show that the rapid decline in transgene expression directed by AAV-CBA results from an inflammatory immune response elicited by the AAV-CBA vector. The AAV-GPE-treated G6pc(-/-) mice exhibit normal levels of blood glucose, blood metabolites, hepatic glycogen, and hepatic fat. Moreover, the mice maintained normal blood glucose levels even after 6 hours of fasting. The complete normalization of hepatic G6Pase-v deficiency by the G6PC promoter/enhancer holds promise for the future of gene therapy in human GSD-Ia patients.
C1 [Yiu, Wai Han; Lee, Young Mok; Peng, Wen-Tao; Pan, Chi-Jiunn; Mead, Paul A.; Mansfield, Brian C.; Chou, Janice Y.] NICHHD, Sect Cellular Differentiat, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
RP Chou, JY (reprint author), NICHHD, Sect Cellular Differentiat, Program Dev Endocrinol & Genet, NIH, Bldg 10,Room 9D42,10 Ctr Dr, Bethesda, MD 20892 USA.
EM chouja@mail.nih.gov
OI Mansfield, Brian/0000-0002-8533-2789
FU NICHD, NIH; NIDDK, NIH [5P01DK058327-08]; Children's Fund for Glycogen
Storage Disease Research
FX This research was supported by the Intramural Research Program of the
NICHD, NIH and a grant (#5P01DK058327-08) from NIDDK, NIH. We thank The
Children's Fund for Glycogen Storage Disease Research for financially
supporting this work.
NR 29
TC 30
Z9 31
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUN
PY 2010
VL 18
IS 6
BP 1076
EP 1084
DI 10.1038/mt.2010.64
PG 9
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 607ZM
UT WOS:000278545800005
PM 20389290
ER
PT J
AU de la Zerda, A
Liu, ZA
Bodapati, S
Teed, R
Vaithilingam, S
Khuri-Yakub, BT
Chen, XY
Dai, HJ
Gambhir, SS
AF de la Zerda, Adam
Liu, Zhuang
Bodapati, Sunil
Teed, Robert
Vaithilingam, Srikant
Khuri-Yakub, Butrus T.
Chen, Xiaoyuan
Dai, Hongjie
Gambhir, Sanjiv Sam
TI Ultrahigh Sensitivity Carbon Nanotube Agents for Photoacoustic Molecular
Imaging in Living Mice
SO NANO LETTERS
LA English
DT Article
DE Photoacoustic molecular imaging; carbon nanotube
ID IN-VIVO
AB Photoacoustic imaging is an emerging modality that overcomes to a great extent the resolution and depth limitations of optical imaging while maintaining relatively high-contrast. However, since many diseases will not manifest an endogenous photoacoustic contrast, it is essential to develop exogenous photoacoustic contrast agents that can target diseased tissue(s). Here we present a novel photoacoustic contrast agent, Indocyanine Green dye-enhanced single walled carbon nanotube (SWNT-ICG). We conjugated this contrast agent with cyclic Arg-Gly-Asp (RGD) peptides to molecularly target the alpha(nu)beta(3) integrins, which are associated with tumor angiogenesis. Intravenous administration of this tumor-targeted contrast agent to tumor-bearing mice showed significantly higher photoacoustic signal in the tumor than in mice injected with the untargeted contrast agent. The new contrast agent gave a markedly 300 times higher photoacoustic contrast in living tissues than previously reported SWNTs, leading to subnanomolar sensitivities. Finally, we show that the new contrast agent can detect similar to 20 times fewer cancer cells than previously reported SWNTs.
C1 [Liu, Zhuang; Dai, Hongjie] Stanford Univ, Dept Chem, Palo Alto, CA 94305 USA.
[de la Zerda, Adam; Bodapati, Sunil; Teed, Robert; Chen, Xiaoyuan; Gambhir, Sanjiv Sam] Stanford Univ, Dept Radiol, Mol Imaging Program Stanford, Palo Alto, CA 94305 USA.
[de la Zerda, Adam; Bodapati, Sunil; Teed, Robert; Chen, Xiaoyuan; Gambhir, Sanjiv Sam] Stanford Univ, Bio X Program, Palo Alto, CA 94305 USA.
[de la Zerda, Adam; Vaithilingam, Srikant; Khuri-Yakub, Butrus T.] Stanford Univ, Dept Elect Engn, Palo Alto, CA 94305 USA.
[Gambhir, Sanjiv Sam] Stanford Univ, Dept Bioengn, Palo Alto, CA 94305 USA.
[Liu, Zhuang] Soochow Univ, Funct Nano & Soft Mat Lab FUNSOM, Suzhou 215123, Jiangsu, Peoples R China.
[Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, Bethesda, MD 20892 USA.
[Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA.
RP Dai, HJ (reprint author), Stanford Univ, Dept Chem, Palo Alto, CA 94305 USA.
EM hdai1@stanford.edu; sgambhir@stanford.edu
RI Liu, Zhuang/H-4352-2011
OI Liu, Zhuang/0000-0002-1629-1039
FU National Institute of Health (NIH) [NCI CCNE U54 CA119367, NCI ICMIC P50
CA 1 14747]; Canary Foundation; Bio-X Graduate Student Fellowship; DoD
Breast Cancer Research
FX We would like to acknowledge funding from the National Institute of
Health (NIH) grants NCI CCNE U54 CA119367 (SSG), NCI ICMIC P50 CA 1
14747 (SSG), and the Canary Foundation for supporting this work. A.D. is
partially funded from the Bio-X Graduate Student Fellowship and the DoD
Breast Cancer Research Program Predoctoral Traineeship Award. The
authors would also like to thank J. Rosenberg for the statistical
analysis and Omer Oralkan and Te-Jen Ma for useful discussions.
NR 14
TC 131
Z9 132
U1 10
U2 104
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1530-6984
J9 NANO LETT
JI Nano Lett.
PD JUN
PY 2010
VL 10
IS 6
BP 2168
EP 2172
DI 10.1021/nl100890d
PG 5
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied;
Physics, Condensed Matter
SC Chemistry; Science & Technology - Other Topics; Materials Science;
Physics
GA 606TB
UT WOS:000278449200033
PM 20499887
ER
PT J
AU Dobrovolskaia, MA
Neun, BW
Clogston, JD
Ding, H
Ljubimova, J
McNeil, SE
AF Dobrovolskaia, Marina A.
Neun, Barry W.
Clogston, Jeffrey D.
Ding, Hui
Ljubimova, Julia
McNeil, Scott E.
TI Ambiguities in applying traditional Limulus Amebocyte Lysate tests to
quantify endotoxin in nanoparticle formulations
SO NANOMEDICINE
LA English
DT Article
DE endotoxin; in vitro assay; interference; Limulus Amebocyte Lysate;
lipopolysaccharide; nanoparticles; rabbit pyrogen test
ID COLLOIDAL GOLD
AB Nanotechnology is finding increasing application in biology and medicine. As with other pharmaceutical formulations and medical devices intended for use in animals and human patients, contamination of nanoparticles with bacterial endotoxins should be thoroughly investigated before preclinical in vitro and in vivo characterization. Traditional methods to study endotoxin contamination include the in vitro quantitative Limulus amebocyte lysate test and the in vivo qualitative rabbit pyrogen test. Both of these tests have a long history of use for traditional pharmaceuticals and medical devices and are routinely used in drug development. Here we report that nanoparticles often interfere with these traditional endotoxin detection tests and suggest approaches to detect and overcome such interferences.
C1 [Dobrovolskaia, Marina A.; Neun, Barry W.; Clogston, Jeffrey D.; McNeil, Scott E.] NCI, Nanotechnol Characterizat Lab, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Ding, Hui; Ljubimova, Julia] Cedars Sinai Med Ctr, Dept Neurosurg, Los Angeles, CA 90048 USA.
RP Dobrovolskaia, MA (reprint author), NCI, Nanotechnol Characterizat Lab, SAIC Frederick Inc, Frederick, MD 21702 USA.
EM marina@mail.nih.gov
RI Nanotechnology Characterization Lab, NCL/K-8454-2012
FU National Cancer Institute, NIH [N01-CO-12400, HHSN261200800001E];
NIH/NCI R01 [CA 123495]
FX The study was supported in whole or in part by federal fiends from the
National Cancer Institute, NIH, under contract N01-CO-12400 and
HHSN261200800001E, and by NIH/NCI R01 grant CA 123495 (Julia Ljubimova).
The content of this publication does not necessarily reflect the views
or policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products or organizations imply
endorsement by the US Government. The authors have no 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 24
TC 40
Z9 40
U1 1
U2 22
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1743-5889
J9 NANOMEDICINE-UK
JI Nanomedicine
PD JUN
PY 2010
VL 5
IS 4
BP 555
EP 562
DI 10.2217/NNM.10.29
PG 8
WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology
SC Biotechnology & Applied Microbiology; Science & Technology - Other
Topics
GA 612WT
UT WOS:000278937100007
PM 20528451
ER
PT J
AU Sanna, S
Pitzalis, M
Zoledziewska, M
Zara, I
Sidore, C
Murru, R
Whalen, MB
Busonero, F
Maschio, A
Costa, G
Melis, MC
Deidda, F
Poddie, F
Morelli, L
Farina, G
Li, Y
Dei, M
Lai, S
Mulas, A
Cuccuru, G
Porcu, E
Liang, LM
Zavattari, P
Moi, L
Deriu, E
Urru, MF
Bajorek, M
Satta, MA
Cocco, E
Ferrigno, P
Sotgiu, S
Pugliatti, M
Traccis, S
Angius, A
Melis, M
Rosati, G
Abecasis, GR
Uda, M
Marrosu, MG
Schlessinger, D
Cucca, F
AF Sanna, Serena
Pitzalis, Maristella
Zoledziewska, Magdalena
Zara, Ilenia
Sidore, Carlo
Murru, Raffaele
Whalen, Michael B.
Busonero, Fabio
Maschio, Andrea
Costa, Gianna
Melis, Maria Cristina
Deidda, Francesca
Poddie, Fausto
Morelli, Laura
Farina, Gabriele
Li, Yun
Dei, Mariano
Lai, Sandra
Mulas, Antonella
Cuccuru, Gianmauro
Porcu, Eleonora
Liang, Liming
Zavattari, Patrizia
Moi, Loredana
Deriu, Elisa
Urru, M. Francesca
Bajorek, Michele
Satta, Maria Anna
Cocco, Eleonora
Ferrigno, Paola
Sotgiu, Stefano
Pugliatti, Maura
Traccis, Sebastiano
Angius, Andrea
Melis, Maurizio
Rosati, Giulio
Abecasis, Goncalo R.
Uda, Manuela
Marrosu, Maria Giovanna
Schlessinger, David
Cucca, Francesco
TI Variants within the immunoregulatory CBLB gene are associated with
multiple sclerosis
SO NATURE GENETICS
LA English
DT Article
ID CELL ANERGY INDUCTION; SUSCEPTIBILITY LOCI; NEGATIVE REGULATION;
ACTIVATION
AB A genome-wide association scan of similar to 6.6 million genotyped or imputed variants in 882 Sardinian individuals with multiple sclerosis (cases) and 872 controls suggested association of CBLB gene variants with disease, which was confirmed in 1,775 cases and 2,005 controls (rs9657904, overall P = 1.60 x 10(-10), OR = 1.40). CBLB encodes a negative regulator of adaptive immune responses, and mice lacking the ortholog are prone to experimental autoimmune encephalomyelitis, the animal model of multiple sclerosis.
C1 [Sanna, Serena; Sidore, Carlo; Busonero, Fabio; Maschio, Andrea; Dei, Mariano; Lai, Sandra; Mulas, Antonella; Cuccuru, Gianmauro; Porcu, Eleonora; Uda, Manuela; Cucca, Francesco] CNR, Ist Neurogenet & Neurofarmacol, Monserrato, Italy.
[Pitzalis, Maristella; Zoledziewska, Magdalena; Deidda, Francesca; Poddie, Fausto; Morelli, Laura; Deriu, Elisa; Cucca, Francesco] Univ Sassari, Dipartimento Sci Biomed, I-07100 Sassari, Italy.
[Zara, Ilenia] Ctr Adv Studies Res & Dev Sardinia CRS4, Lab Bioinformat, Pula, Italy.
[Sidore, Carlo; Whalen, Michael B.; Urru, M. Francesca; Angius, Andrea] CRS4, Lab Genom, Pula, Italy.
[Murru, Raffaele; Costa, Gianna; Melis, Maria Cristina; Moi, Loredana; Cocco, Eleonora; Marrosu, Maria Giovanna] Univ Cagliari, Dipartimento Sci Neurol & Cardiovasc, Ctr Sclerosi Multipla, Cagliari, Italy.
[Farina, Gabriele; Sotgiu, Stefano; Pugliatti, Maura; Rosati, Giulio] Univ Sassari, Ist Clin Neurol, I-07100 Sassari, Italy.
[Li, Yun; Liang, Liming; Abecasis, Goncalo R.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Li, Yun] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Li, Yun] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA.
[Liang, Liming] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Liang, Liming] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Zavattari, Patrizia] Univ Cagliari, Dipartimento Sci Biomed & Biotecnol, Cagliari, Italy.
[Bajorek, Michele] Azienda Osped Brotzu, Ctr Trasfusionale, Cagliari, Italy.
[Satta, Maria Anna] Azienda Sanit Locale 1, Sassari, Italy.
[Ferrigno, Paola; Melis, Maurizio] Azienda Osped Brotzu, Div Neurol, Cagliari, Italy.
[Traccis, Sebastiano] Presidio Osped, Div Neurol, Ozieri, Italy.
[Schlessinger, David] NIA, Genet Lab, Baltimore, MD 21224 USA.
RP Cucca, F (reprint author), CNR, Ist Neurogenet & Neurofarmacol, Monserrato, Italy.
EM francesco.cucca@inn.cnr.it
RI Abecasis, Goncalo/B-7840-2010; Cocco, Eleonora/G-5064-2012; Angius,
Andrea/B-8966-2015; Angius, Andrea/P-9549-2015;
OI sanna, serena/0000-0002-3768-1749; Abecasis,
Goncalo/0000-0003-1509-1825; Marrosu, Maria
Giovanna/0000-0003-2334-2081; Cocco, Eleonora/0000-0002-3878-8820;
Angius, Andrea/0000-0003-2596-6461; Angius, Andrea/0000-0001-9372-1162;
Mulas, Antonella/0000-0002-6856-1483; Pitzalis,
Maristella/0000-0003-4975-6987; WHALEN,
MICHAELBERNARD/0000-0001-7300-8511; Sidore, Carlo/0000-0001-7504-7477
FU Fondazione Italiana Sclerosi Multipla (FISM) [Cod. 2008/R/7]; Italian
Ministry of Scientific Research (MIUR) [2007KXNKNP]; US National
Institutes of Health [NO1-AG-1-2109]; National Institute of Aging (NIA);
NIH [HG002651, HG005214, MH084698]
FX This study was supported by the Fondazione Italiana Sclerosi Multipla
(FISM) Cod. 2008/R/7 to F.C., by the Italian Ministry of Scientific
Research (MIUR grant 2007KXNKNP) and by US National Institutes of Health
contract NO1-AG-1-2109 from National Institute of Aging (NIA) to the
SardiNIA ('ProgeNIA') team. The contributions of G.R.A., Y.L. and L.L.
were supported in part by NIH grants HG002651, HG005214 and MH084698.
NR 14
TC 85
Z9 88
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD JUN
PY 2010
VL 42
IS 6
BP 495
EP 497
DI 10.1038/ng.584
PG 3
WC Genetics & Heredity
SC Genetics & Heredity
GA 601RN
UT WOS:000278081500013
PM 20453840
ER
PT J
AU Stahl, EA
Raychaudhuri, S
Remmers, EF
Xie, G
Eyre, S
Thomson, BP
Li, YH
Kurreeman, FAS
Zhernakova, A
Hinks, A
Guiducci, C
Chen, R
Alfredsson, L
Amos, CI
Ardlie, KG
Barton, A
Bowes, J
Brouwer, E
Burtt, NP
Catanese, JJ
Coblyn, J
Coenen, MJH
Costenbader, KH
Criswell, LA
Crusius, JBA
Cui, J
de Bakker, PIW
De Jager, PL
Ding, B
Emery, P
Flynn, E
Harrison, P
Hocking, LJ
Huizinga, TWJ
Kastner, DL
Ke, XY
Lee, AT
Liu, XD
Martin, P
Morgan, AW
Padyukov, L
Posthumus, MD
Radstake, TRDJ
Reid, DM
Seielstad, M
Seldin, MF
Shadick, NA
Steer, S
Tak, PP
Thomson, W
van der Helm-van Mil, AHM
van der Horst-Bruinsma, IE
van der Schoot, CE
van Riel, PLCM
Weinblatt, ME
Wilson, AG
Wolbink, GJ
Wordsworth, BP
Wijmenga, C
Karlson, EW
Toes, REM
de Vries, N
Begovich, AB
Worthington, J
Siminovitch, KA
Gregersen, PK
Klareskog, L
Plenge, RM
AF Stahl, Eli A.
Raychaudhuri, Soumya
Remmers, Elaine F.
Xie, Gang
Eyre, Stephen
Thomson, Brian P.
Li, Yonghong
Kurreeman, Fina A. S.
Zhernakova, Alexandra
Hinks, Anne
Guiducci, Candace
Chen, Robert
Alfredsson, Lars
Amos, Christopher I.
Ardlie, Kristin G.
Barton, Anne
Bowes, John
Brouwer, Elisabeth
Burtt, Noel P.
Catanese, Joseph J.
Coblyn, Jonathan
Coenen, Marieke J. H.
Costenbader, Karen H.
Criswell, Lindsey A.
Crusius, J. Bart A.
Cui, Jing
de Bakker, Paul I. W.
De Jager, Philip L.
Ding, Bo
Emery, Paul
Flynn, Edward
Harrison, Pille
Hocking, Lynne J.
Huizinga, Tom W. J.
Kastner, Daniel L.
Ke, Xiayi
Lee, Annette T.
Liu, Xiangdong
Martin, Paul
Morgan, Ann W.
Padyukov, Leonid
Posthumus, Marcel D.
Radstake, Timothy R. D. J.
Reid, David M.
Seielstad, Mark
Seldin, Michael F.
Shadick, Nancy A.
Steer, Sophia
Tak, Paul P.
Thomson, Wendy
van der Helm-van Mil, Annette H. M.
van der Horst-Bruinsma, Irene E.
van der Schoot, C. Ellen
van Riel, Piet L. C. M.
Weinblatt, Michael E.
Wilson, Anthony G.
Wolbink, Gert Jan
Wordsworth, B. Paul
Wijmenga, Cisca
Karlson, Elizabeth W.
Toes, Rene E. M.
de Vries, Niek
Begovich, Ann B.
Worthington, Jane
Siminovitch, Katherine A.
Gregersen, Peter K.
Klareskog, Lars
Plenge, Robert M.
CA BIRAC Consortium
YEAR Consortium
TI Genome-wide association study meta-analysis identifies seven new
rheumatoid arthritis risk loci
SO NATURE GENETICS
LA English
DT Article
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; SUSCEPTIBILITY LOCI; CELIAC-DISEASE;
VARIANTS; GENE; COMMON; REGION; POLYMORPHISMS; CONFIRMATION; REPLICATION
AB To identify new genetic risk factors for rheumatoid arthritis, we conducted a genome-wide association study meta-analysis of 5,539 autoantibody-positive individuals with rheumatoid arthritis (cases) and 20,169 controls of European descent, followed by replication in an independent set of 6,768 rheumatoid arthritis cases and 8,806 controls. Of 34 SNPs selected for replication, 7 new rheumatoid arthritis risk alleles were identified at genome-wide significance (P < 5 x 10(-8)) in an analysis of all 41,282 samples. The associated SNPs are near genes of known immune function, including IL6ST, SPRED2, RBPJ, CCR6, IRF5 and PXK. We also refined associations at two established rheumatoid arthritis risk loci (IL2RA and CCL21) and confirmed the association at AFF3. These new associations bring the total number of confirmed rheumatoid arthritis risk loci to 31 among individuals of European ancestry. An additional 11 SNPs replicated at P < 0.05, many of which are validated autoimmune risk alleles, suggesting that most represent genuine rheumatoid arthritis risk alleles.
C1 [Stahl, Eli A.; Raychaudhuri, Soumya; Kurreeman, Fina A. S.; Chen, Robert; Coblyn, Jonathan; Costenbader, Karen H.; Cui, Jing; Shadick, Nancy A.; Weinblatt, Michael E.; Karlson, Elizabeth W.; Plenge, Robert M.] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA.
[Stahl, Eli A.; Raychaudhuri, Soumya; Thomson, Brian P.; Kurreeman, Fina A. S.; Guiducci, Candace; Ardlie, Kristin G.; Burtt, Noel P.; de Bakker, Paul I. W.; De Jager, Philip L.; Plenge, Robert M.] Broad Inst, Cambridge, MA USA.
[Raychaudhuri, Soumya] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Remmers, Elaine F.; Kastner, Daniel L.] NIAMSD, Genet & Genom Branch, US NIH, Bethesda, MD 20892 USA.
[Xie, Gang; Liu, Xiangdong; Siminovitch, Katherine A.] Univ Toronto, Mt Sinai Hosp, Dept Med, Toronto, ON M5G 1X5, Canada.
[Xie, Gang; Liu, Xiangdong; Siminovitch, Katherine A.] Univ Hlth Network, Toronto, ON, Canada.
[Eyre, Stephen; Hinks, Anne; Barton, Anne; Bowes, John; Flynn, Edward; Ke, Xiayi; Martin, Paul; Thomson, Wendy; Worthington, Jane] Univ Manchester, Arthrit Res UK Epidemiol Unit, Manchester, Lancs, England.
[Li, Yonghong; Catanese, Joseph J.; Begovich, Ann B.] Celera, Alameda, CA USA.
[Kurreeman, Fina A. S.; Huizinga, Tom W. J.; van der Helm-van Mil, Annette H. M.; Toes, Rene E. M.] Leiden Univ, Med Ctr, Dept Rheumatol, Leiden, Netherlands.
[Zhernakova, Alexandra; Wijmenga, Cisca] Univ Med Ctr Groningen, Dept Genet, NL-9713 AV Groningen, Netherlands.
[Zhernakova, Alexandra; Brouwer, Elisabeth; Posthumus, Marcel D.; Wijmenga, Cisca] Univ Groningen, Groningen, Netherlands.
[Alfredsson, Lars; Ding, Bo] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden.
[Amos, Christopher I.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Brouwer, Elisabeth; Posthumus, Marcel D.] Univ Med Ctr Groningen, Dept Rheumatol & Clin Immunol, NL-9713 AV Groningen, Netherlands.
[Coenen, Marieke J. H.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands.
[Criswell, Lindsey A.] Univ Calif San Francisco, Dept Med, Rosalind Russell Med Res Ctr Arthrit, San Francisco, CA USA.
[Crusius, J. Bart A.] Vrije Univ Amsterdam, Med Ctr, Dept Pathol, Immunogenet Lab, Amsterdam, Netherlands.
[de Bakker, Paul I. W.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA.
[De Jager, Philip L.] Brigham & Womens Hosp, Ctr Neurol Dis, Dept Neurol, Boston, MA 02115 USA.
[Emery, Paul; Morgan, Ann W.] Univ Leeds, Leeds Inst Mol Med, Leeds Musculoskeletal Biomed Res Unit, Natl Inst Hlth Res, Leeds, W Yorkshire, England.
[Harrison, Pille; Wordsworth, B. Paul] Univ Oxford, Inst Musculoskeletal Sci, Botnar Res Ctr, Oxford, England.
[Hocking, Lynne J.; Reid, David M.] Univ Aberdeen, Div Appl Med, Musculoskeletal & Genet Sect, Aberdeen, Scotland.
[Lee, Annette T.; Gregersen, Peter K.] N Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA.
[Padyukov, Leonid; Klareskog, Lars] Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.
[Padyukov, Leonid; Klareskog, Lars] Karolinska Univ Hosp Solna, Stockholm, Sweden.
[Radstake, Timothy R. D. J.; van Riel, Piet L. C. M.] Radboud Univ Nijmegen, Med Ctr, Dept Rheumatol, NL-6525 ED Nijmegen, Netherlands.
[Seielstad, Mark] Genome Inst Singapore, Singapore, Singapore.
[Seldin, Michael F.] Univ Calif Davis, Rowe Program Genet, Davis, CA 95616 USA.
[Steer, Sophia] Kings Coll Hosp Natl Hlth Serv Fdn Trust, Clin & Acad Rheumatol, London, England.
[van der Schoot, C. Ellen; Wolbink, Gert Jan] Univ Amsterdam, Acad Med Ctr, Sanquin Res Landsteiner Lab, NL-1105 AZ Amsterdam, Netherlands.
[van der Horst-Bruinsma, Irene E.] Vrije Univ Amsterdam, Univ Med Ctr, Dept Rheumatol, Amsterdam, Netherlands.
[Wilson, Anthony G.] Univ Sheffield, Sch Med & Biomed Sci, Sheffield, S Yorkshire, England.
[Wolbink, Gert Jan] Jan van Breemen Inst, Amsterdam, Netherlands.
[Begovich, Ann B.] Roche Diagnost, Pleasanton, CA USA.
RP Plenge, RM (reprint author), Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, 75 Francis St, Boston, MA 02115 USA.
EM rplenge@partners.org
RI Worthington, Jane/M-9770-2014; Barton, Anne/N-2053-2014; Bowes,
John/B-3472-2015; Hinks, Anne/E-1853-2015; Brouwer,
Elisabeth/A-3198-2015; Coenen, Marieke/A-2159-2010; de Vries,
Niek/J-9348-2013; de Bakker, Paul/B-8730-2009; Wijmenga,
Cisca/D-2173-2009; Siminovitch, Katherine/K-1475-2013; Riel,
P.L.C.M./H-8082-2014;
OI Hocking, Lynne J/0000-0002-2414-2826; Alfredsson,
Lars/0000-0003-1688-6697; Seielstad, Mark/0000-0001-5783-1401; Martin,
Paul/0000-0002-1016-6851; Wijmenga, Cisca/0000-0002-5635-1614;
Klareskog, Lars/0000-0001-9601-6186; Thomson, Wendy/0000-0002-9022-5179;
Eyre, Stephen/0000-0002-1251-6974; Worthington,
Jane/0000-0003-0544-042X; Barton, Anne/0000-0003-3316-2527; Bowes,
John/0000-0003-4659-031X; Hinks, Anne/0000-0001-8843-3967; de Vries,
Niek/0000-0002-6257-8604; de Bakker, Paul/0000-0001-7735-7858;
Zhernakova, Alexandra/0000-0002-4574-0841; Padyukov,
Leonid/0000-0003-2950-5670
FU US National Institutes of Health (NIH) [R01-AR057108, R01-AR056768, U54
RR020278]; Fox Trot Fund; William Randolph Hearst Fund of Harvard
University; Burroughs Wellcome Fund; NIH [1K08AR055688-01A1,
NO1-AR-2-2263, RO1 AR44422, R01 AI065841, 5-M01-RR-00079, P01 CA87969,
CA49449, CA67262, CA50385, AR049880-06, AR47782]; American College of
Rheumatology Bridge Grant; EMBO-UNESCO L'Oreal Fellowship; National
Center for Research Resources [U54 RR020278]; Crescendo; Swedish Medical
Research council; Swedish Council for Working Life and Social Research;
Swedish Rheumatism Foundation; Vinnova; AFA; National Institute of
Arthritis; Musculoskeletal and Skin Diseases of the US National
Institutes of Health; Canadian Institutes for Health Research [MOP79321,
IIN-84042]; Ontario Research Fund [RE01061]; Canada Research Chair;
Arthritis Research campaign arc [17552]; Manchester Biomedical Research
Centre; Manchester Academy of Health Sciences; Netherlands Organization
for Scientific Research (VICI) [918.66.620]; Existing Epidemiological
Data (STAMPEED) genomics research program [R01HL087676]; National Center
for Research Resources; Biogen-Idec; King Gustaf V's 80-year foundation;
US National Institutes of Health and National Heart, Lung, and Blood
Institute; Stockholm County Council
FX R. M. P. is supported by grants from the US National Institutes of
Health (NIH) (R01-AR057108, R01-AR056768 and U54 RR020278), a private
donation from the Fox Trot Fund, the William Randolph Hearst Fund of
Harvard University, the American College of Rheumatology 'Within Our
Reach' campaign and a Career Award for Medical Scientists from the
Burroughs Wellcome Fund. S. R. is supported by an NIH Career Development
Award (1K08AR055688-01A1) and an American College of Rheumatology Bridge
Grant. F. A. S. K. is supported by an EMBO-UNESCO L'Oreal Fellowship.
The Broad Institute Center for Genotyping and Analysis is supported by
grant U54 RR020278 from the National Center for Research Resources. The
BRASS Registry is supported by a grant from Crescendo and Biogen-Idec.
EIRA is supported by grants from the Swedish Medical Research council,
the Swedish Council for Working Life and Social Research, King Gustaf
V's 80-year foundation, the Swedish Rheumatism Foundation, Stockholm
County Council, from Vinnova and the insurance company AFA. NARAC is
supported by the NIH (NO1-AR-2-2263 and RO1 AR44422). L. A. C. is
supported by the NIH (R01 AI065841 and). The Nurses Health Study is
supported by NIH grants P01 CA87969, CA49449, CA67262, CA50385,
AR049880-06 and AR47782. This research was also supported in part by the
Intramural Research Program of the National Institute of Arthritis,
Musculoskeletal and Skin Diseases of the US National Institutes of
Health. This research was also supported in part by grants to K. A. S.
from the Canadian Institutes for Health Research (MOP79321 and
IIN-84042) and the Ontario Research Fund (RE01061) and by a Canada
Research Chair. Genotyping of United Kingdom Rheumatoid Arthritis
Genetics samples was supported by the Arthritis Research campaign arc
grant reference number 17552 and by the Manchester Biomedical Research
Centre and Manchester Academy of Health Sciences. C. W. was funded by
the Netherlands Organization for Scientific Research (VICI grant
918.66.620). We acknowledge the help of B. A. C. Dijkmans, D. van
Schaardenburg, A. Salvador Pena, P. L. Klarenbeek, Z. Zhang, M. T.
Nurmohamed, W. F. Lems, R.R.J. van de Stadt, W. H. Bos, J. Ursum, M. G.
M. Bartelds, D. M. Gerlag, M. G. H. van der Sande, C. A. Wijbrandts and
M. M. J. Herenius in gathering Genetics Network Rheumatology Amsterdam
subject samples and data. We thank the Myocardial Infarction Genetics
Consortium (MIGen) study for the use of genotype data from their healthy
controls in our study. The MIGen study was funded by the US National
Institutes of Health and National Heart, Lung, and Blood Institute's SNP
Typing for Association with Multiple Phenotypes from Existing
Epidemiological Data (STAMPEED) genomics research program R01HL087676
and a grant from the National Center for Research Resources. We thank J.
Seddon, Progression of AMD Study, Age-Related Macular Degeneration (AMD)
Registry Study, Family Study of AMD, The US Twin Study of AMD and the
Age-Related Eye Disease Study (AREDS) for use of genotype data from
their healthy controls in our study. We thank D. Hafler and the Multiple
Sclerosis Collaborative for use of genotype data from their healthy
controls recruited at Brigham and Women's Hospital.
NR 57
TC 600
Z9 609
U1 5
U2 69
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD JUN
PY 2010
VL 42
IS 6
BP 508
EP U56
DI 10.1038/ng.582
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 601RN
UT WOS:000278081500016
PM 20453842
ER
PT J
AU Beaty, TH
Murray, JC
Marazita, ML
Munger, RG
Ruczinski, I
Hetmanski, JB
Liang, KY
Wu, T
Murray, T
Fallin, MD
Redett, RA
Raymond, G
Schwender, H
Jin, SC
Cooper, ME
Dunnwald, M
Mansilla, MA
Leslie, E
Bullard, S
Lidral, AC
Moreno, LM
Menezes, R
Vieira, AR
Petrin, A
Wilcox, AJ
Lie, RT
Jabs, EW
Wu-Chou, YH
Chen, PK
Wang, H
Ye, XQ
Huang, SZ
Yeow, V
Chong, SS
Jee, SH
Shi, B
Christensen, K
Melbye, M
Doheny, KF
Pugh, EW
Ling, H
Castilla, EE
Czeizel, AE
Ma, L
Field, LL
Brody, L
Pangilinan, F
Mills, JL
Molloy, AM
Kirke, PN
Scott, JM
Arcos-Burgos, M
Scott, AF
AF Beaty, Terri H.
Murray, Jeffrey C.
Marazita, Mary L.
Munger, Ronald G.
Ruczinski, Ingo
Hetmanski, Jacqueline B.
Liang, Kung Yee
Wu, Tao
Murray, Tanda
Fallin, M. Daniele
Redett, Richard A.
Raymond, Gerald
Schwender, Holger
Jin, Sheng-Chih
Cooper, Margaret E.
Dunnwald, Martine
Mansilla, Maria A.
Leslie, Elizabeth
Bullard, Stephen
Lidral, Andrew C.
Moreno, Lina M.
Menezes, Renato
Vieira, Alexandre R.
Petrin, Aline
Wilcox, Allen J.
Lie, Rolv T.
Jabs, Ethylin W.
Wu-Chou, Yah Huei
Chen, Philip K.
Wang, Hong
Ye, Xiaoqian
Huang, Shangzhi
Yeow, Vincent
Chong, Samuel S.
Jee, Sun Ha
Shi, Bing
Christensen, Kaare
Melbye, Mads
Doheny, Kimberly F.
Pugh, Elizabeth W.
Ling, Hua
Castilla, Eduardo E.
Czeizel, Andrew E.
Ma, Lian
Field, L. Leigh
Brody, Lawrence
Pangilinan, Faith
Mills, James L.
Molloy, Anne M.
Kirke, Peadar N.
Scott, James M.
Arcos-Burgos, Mauricio
Scott, Alan F.
TI A genome-wide association study of cleft lip with and without cleft
palate identifies risk variants near MAFB and ABCA4
SO NATURE GENETICS
LA English
DT Article
ID INTERFERON-REGULATORY-FACTOR-6 IRF6; UNIFIED APPROACH; RELATIVES;
COHORT; MARKER; TESTS
AB Case-parent trios were used in a genome-wide association study of cleft lip with and without cleft palate. SNPs near two genes not previously associated with cleft lip with and without cleft palate (MAFB, most significant SNP rs13041247, with odds ratio (OR) per minor allele = 0.704, 95% CI 0.635-0.778, P = 1.44 x 10(-11); and ABCA4, most significant SNP rs560426, with OR = 1.432, 95% CI 1.292-1.587, P = 5.01 x 10(-12)) and two previously identified regions (at chromosome 8q24 and IRF6) attained genome-wide significance. Stratifying trios into European and Asian ancestry groups revealed differences in statistical significance, although estimated effect sizes remained similar. Replication studies from several populations showed confirming evidence, with families of European ancestry giving stronger evidence for markers in 8q24, whereas Asian families showed stronger evidence for association with MAFB and ABCA4. Expression studies support a role for MAFB in palatal development.
C1 [Beaty, Terri H.; Ruczinski, Ingo; Hetmanski, Jacqueline B.; Liang, Kung Yee; Wu, Tao; Murray, Tanda; Fallin, M. Daniele; Schwender, Holger; Jin, Sheng-Chih] Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD 21218 USA.
[Murray, Jeffrey C.; Dunnwald, Martine; Mansilla, Maria A.; Leslie, Elizabeth; Petrin, Aline] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA.
[Marazita, Mary L.; Cooper, Margaret E.; Menezes, Renato; Vieira, Alexandre R.] Univ Pittsburgh, Sch Dent Med, Pittsburgh, PA USA.
[Munger, Ronald G.] Utah State Univ, Logan, UT 84322 USA.
[Wu, Tao] Peking Univ, Hlth Sci Ctr, Beijing 100871, Peoples R China.
[Redett, Richard A.; Raymond, Gerald; Jabs, Ethylin W.; Wang, Hong; Scott, Alan F.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Bullard, Stephen; Lidral, Andrew C.; Moreno, Lina M.] Univ Iowa, Dept Orthodont, Iowa City, IA USA.
[Wilcox, Allen J.] NIEHS, NIH, Durham, NC USA.
[Lie, Rolv T.] Univ Bergen, Bergen, Norway.
[Jabs, Ethylin W.; Ye, Xiaoqian] Mt Sinai Sch Med, New York, NY USA.
[Wu-Chou, Yah Huei; Chen, Philip K.] Chang Gung Mem Hosp, Tao Yuan, Taiwan.
[Ye, Xiaoqian] Wuhan Univ, Wuhan 430072, Peoples R China.
[Huang, Shangzhi] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Yeow, Vincent] KK Womens & Childrens Hosp, Singapore, Singapore.
[Chong, Samuel S.] Natl Univ Singapore, Singapore 117548, Singapore.
[Jee, Sun Ha] Yonsei Univ, Seoul 120749, South Korea.
[Shi, Bing] Sichuan Univ, W China Sch Stomatol, Chengdu 610064, Peoples R China.
[Christensen, Kaare] Univ So Denmark, Odense, Denmark.
[Melbye, Mads] Statens Serum Inst, DK-2300 Copenhagen, Denmark.
[Doheny, Kimberly F.; Pugh, Elizabeth W.; Ling, Hua] Johns Hopkins Univ, Ctr Inherited Dis Res, Baltimore, MD USA.
[Castilla, Eduardo E.] Fundacao Oswaldo Cruz FIOCRUZ, Dept Genet, Rio De Janeiro, Brazil.
[Czeizel, Andrew E.] Fdn Community Control Hereditary Dis, Budapest, Hungary.
[Ma, Lian] Beijing Univ, Sch Stomatol, Beijing 100871, Peoples R China.
[Field, L. Leigh] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada.
[Brody, Lawrence; Pangilinan, Faith] NHGRI, NIH, Bethesda, MD 20892 USA.
[Mills, James L.] NICHHD, NIH, Bethesda, MD 20892 USA.
[Molloy, Anne M.; Scott, James M.] Trinity Coll Dublin, Dublin, Ireland.
[Kirke, Peadar N.] Hlth Res Board, Dublin, Ireland.
[Arcos-Burgos, Mauricio] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
RP Beaty, TH (reprint author), Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD 21218 USA.
EM tbeaty@jhsph.edu
RI Liang, Kung-Yee/F-8299-2011; Inagemp, Inct/J-9451-2013; Christensen,
Kaare/C-2360-2009; Chong, Samuel/D-8098-2015;
OI Christensen, Kaare/0000-0002-5429-5292; Molloy,
Anne/0000-0002-1688-9049; Wilcox, Allen/0000-0002-3376-1311; Jabs,
Ethylin/0000-0001-8983-5466
FU National Institute for Dental and Craniofacial Research [U01-DE-018993];
International Consortium to Identify Genes and Interactions Controlling
Oral Clefts [2007 2009]; National Human Genome Research Institute
(NHGRI); US National Institutes of Health (NIH) [HHSN268200782096C];
March of Dimes Basil O'Connor award [FY 98-0718]; Research Grant
[6-FY01-61]; NIH [R03-AR-055313, P50-DE-16215, K99-DE-018441]; Canadian
Institutes of Health Research [MT-11263]; NIH National Institute of
Environmental Health Sciences; [R01-DE-014581]; [R37-DE08559];
[R01-DE09886]; [R01-DE012472]; [R01-DE014677]; [R01-DE016148];
[P50-DE016215]; [R21-DE016930]; [R01-HD390661]; [R01-DE016877];
[JK02-AEO15291]
FX We sincerely thank all of the families at each recruitment site for
participating in this study, and we gratefully acknowledge the
invaluable assistance of clinical, field and laboratory staff who
contributed to making this work possible. We are particularly grateful
to K. Durda and J. L'Heureux of the University of Iowa for assistance
with samples and phenotype data; L. Henkle for technical assistance; J.
Resick, C. Brandon and K. Bardi of the University of Pittsburgh for
assistance with recruitment; W. Carricato, K. Deeley and J. Ruff of the
University of Pittsburgh for sample handling; P. Patel and M. Rose of
Johns Hopkins for assistance with data analysis; F. Cheah of the
National University of Singapore for sample processing and management;
M. Feldkamp and J. Carey of the Utah Birth Defects Network for
assistance with recruitment and case review; and D. Pearce of the Utah
State University for sample collection and processing. Funding to
support data collection, genotyping and analysis came from several
sources, some to individual investigators and some to the consortium
itself. The consortium for GWAS genotyping and analysis was supported by
the National Institute for Dental and Craniofacial Research through
U01-DE-018993; the International Consortium to Identify Genes and
Interactions Controlling Oral Clefts, 2007 2009. This project was part
of the Gene, Environment Association Studies Consortium (GENEVA) funded
by the National Human Genome Research Institute (NHGRI) to enhance
communication and collaboration among investigators conducting
genome-wide studies for a variety of complex diseases. Our group
benefited greatly from the work and efforts of the entire consortium,
especially the work by the Coordinating Center (directed by B. Weir and
C. Laurie of the University of Washington) in data cleaning and
preparation of these case-parent trios for submission to the Database
for Genotypes and Phenotypes (dbGaP). We also acknowledge the leadership
of T. Manolio of NHGRI and E. Harris of National Institute of Dental and
Craniofacial Research. Genotyping services were provided by the Center
for Inherited Disease Research (CIDR), funded through a federal contract
from the US National Institutes of Health (NIH) to Johns Hopkins
University (contract number HHSN268200782096C). Funding for individual
investigators and the replication studies include: R01-DE-014581 (T. H.
B.); R37-DE08559 (J. C. M. and M. L. M.), R01-DE09886 (M. L. M., L. M.
and L. L. F.), R01-DE012472 (M. L. M.), R01-DE014677 (A. C. L. and M. L.
M.), R01-DE016148 (M. L. M.), P50-DE016215 (J. C. M. and M. L. M.),
R21-DE016930 (M. L. M., E. E. C. and A. E. C.), R01-HD390661 and
R01-DE016877 (R. G. M.). JK02-AEO15291 (A. C. L.), March of Dimes Basil
O'Connor award #FY 98-0718 and Research Grant #6-FY01-61 (A. C. L.); NIH
R03-AR-055313 and NIH P50-DE-16215 (project #3) (M. D.), K99-DE-018441
(R. M.); and the Canadian Institutes of Health Research MT-11263 (L. L.
F.). The Smile Train Foundation supported data collection in Chengdu
(E.W.J. and B. S.). This research was supported in part by the
Intramural Research Program of the NIH National Institute of
Environmental Health Sciences (A.J.W.).
NR 22
TC 213
Z9 230
U1 2
U2 24
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD JUN
PY 2010
VL 42
IS 6
BP 525
EP U76
DI 10.1038/ng.580
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 601RN
UT WOS:000278081500019
PM 20436469
ER
PT J
AU Weller, ML
Amornphimoltham, P
Schmidt, M
Wilson, PA
Gutkind, JS
Chiorini, JA
AF Weller, Melodie L.
Amornphimoltham, Panomwat
Schmidt, Michael
Wilson, Paul A.
Gutkind, J. Silvio
Chiorini, John A.
TI Epidermal growth factor receptor is a co-receptor for adeno-associated
virus serotype 6
SO NATURE MEDICINE
LA English
DT Article
ID PROTEIN-TYROSINE KINASE; GENE-EXPRESSION; MOUSE LUNG; VECTORS;
TRANSDUCTION; EGFR; CELLS
AB A key step in gene therapy is the efficient transfer of genes in a cell type- and tissue-specific manner. To better understand the mechanism of adeno-associated virus serotype 6 (AAV6) transduction, we used comparative gene analysis (CGA) combined with pathway visualization software to identify a positive correlation between AAV6 transduction and epidermal growth factor receptor (EGFR) expression. Subsequent experiments suggested that EGFR is necessary for vector internalization and probably functions as a co-receptor for AAV6.
C1 [Weller, Melodie L.; Schmidt, Michael; Chiorini, John A.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, US Natl Inst Hlth NIH, Bethesda, MD USA.
[Amornphimoltham, Panomwat; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
[Wilson, Paul A.] NIH, Custom Applicat Branch, Div Enterprise & Custom Applicat, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Chiorini, JA (reprint author), Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, US Natl Inst Hlth NIH, Bethesda, MD USA.
EM jchiorini@dir.nidcr.nih.gov
RI Gutkind, J. Silvio/A-1053-2009
FU Intramural NIH HHS [Z01 DE000695-09]
NR 15
TC 43
Z9 43
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD JUN
PY 2010
VL 16
IS 6
BP 662
EP 664
DI 10.1038/nm.2145
PG 3
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 606BA
UT WOS:000278394200031
PM 20473307
ER
PT J
AU Charles, N
Hardwick, D
Daugas, E
Illei, GG
Rivera, J
AF Charles, Nicolas
Hardwick, Donna
Daugas, Eric
Illei, Gabor G.
Rivera, Juan
TI Basophils and the T helper 2 environment can promote the development of
lupus nephritis
SO NATURE MEDICINE
LA English
DT Article
ID LYN-DEFICIENT MICE; MRL-LPR MICE; T-CELLS; AUTOIMMUNE-DISEASE; REVISED
CRITERIA; INTERFERON-GAMMA; IMMUNOGLOBULIN-E; RENAL-DISEASE; MURINE
LUPUS; MAST-CELLS
AB In systemic lupus erythematosus (SLE), self-reactive antibodies can target the kidney (lupus nephritis), leading to functional failure and possible mortality. We report that activation of basophils by autoreactive IgE causes their homing to lymph nodes, promoting T helper type 2 (T(H)2) cell differentiation and enhancing the production of self-reactive antibodies that cause lupus-like nephritis in mice lacking the Src family protein tyrosine kinase Lyn (Lyn(-/-) mice). Individuals with SLE also have elevated serum IgE, self-reactive IgEs and activated basophils that express CD62 ligand (CD62L) and the major histocompatibility complex (MHC) class II molecule human leukocyte antigen-DR (HLA-DR), parameters that are associated with increased disease activity and active lupus nephritis. Basophils were also present in the lymph nodes and spleen of subjects with SLE. Thus, in Lyn(-/-) mice, basophils and IgE autoantibodies amplify autoantibody production that leads to lupus nephritis, and in individuals with SLE IgE autoantibodies and activated basophils are factors associated with disease activity and nephritis.
C1 [Charles, Nicolas; Rivera, Juan] NIAMSD, Immunogenet Mol Lab, NIH, Bethesda, MD 20892 USA.
[Hardwick, Donna] NIAMS, Off Clin Director, NIH, Bethesda, MD USA.
[Daugas, Eric] Univ Paris Diderot, Inst Natl Sante & Rech Med U699, Dept Nephrol, Assistance Publ Hop Paris,Hop Bichat, Paris, France.
[Illei, Gabor G.] Natl Inst Dent & Craniofacial Res, Sjogrens Syndrome Clin, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA.
RP Rivera, J (reprint author), NIAMSD, Immunogenet Mol Lab, NIH, Bethesda, MD 20892 USA.
EM juan_rivera@nih.gov
RI Charles, Nicolas/P-5430-2014
OI Charles, Nicolas/0000-0002-5416-5834
FU Laboratory Animal Care and Use Section; Flow Cytometry Section of the
Office of Science and Technology, NIAMS; National Institute of Dental
and Craniofacial Research, NIH
FX We thank J. Daruwalla and G. Souto-Adeva (Office of the Clinical
Director, NIAMS) for human samples, data input and analysis and H. C.
Oettgen (Harvard University) for providing the Igh-7-/- mice.
We also thank M. Hourseau for human sample preparation and L. B.
Schwartz (Virginia Commonwealth University) and A. F. Walls (University
of Southampton) for the gift of human basophil-specific monoclonal
antibodies. We acknowledge the support of the Laboratory Animal Care and
Use Section and the Flow Cytometry Section of the Office of Science and
Technology, NIAMS. This research was supported by the intramural
programs of NIAMS and National Institute of Dental and Craniofacial
Research, NIH.
NR 57
TC 140
Z9 147
U1 1
U2 12
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD JUN
PY 2010
VL 16
IS 6
BP 701
EP U107
DI 10.1038/nm.2159
PG 8
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 606BA
UT WOS:000278394200037
PM 20512127
ER
PT J
AU Ryan, BM
Robles, AI
Harris, CC
AF Ryan, Brid M.
Robles, Ana I.
Harris, Curtis C.
TI Genetic variation in microRNA networks: the implications for cancer
research
SO NATURE REVIEWS CANCER
LA English
DT Review
ID SINGLE-NUCLEOTIDE POLYMORPHISMS; CHRONIC LYMPHOCYTIC-LEUKEMIA;
THYMIDYLATE-SYNTHASE GENE; BINDING-SITE POLYMORPHISM; BREAST-CANCER;
MESSENGER-RNA; LUNG-CANCER; TARGET SITE; POSTTRANSCRIPTIONAL REGULATION;
HEPATOCELLULAR-CARCINOMA
AB Many studies have highlighted the role that microRNAs have in physiological processes and how their deregulation can lead to cancer. More recently, it has been proposed that the presence of single nucleotide polymorphisms in microRNA genes, their processing machinery and target binding sites affects cancer risk, treatment efficacy and patient prognosis. In reviewing this new field of cancer biology, we describe the methodological approaches of these studies and make recommendations for which strategies will be most informative in the future.
C1 [Ryan, Brid M.; Robles, Ana I.; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Ryan, Brid M.] NCI, Canc Prevent Fellowship Program, Ctr Canc Training, NIH, Bethesda, MD 20892 USA.
RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, 37 Convent Dr,Bldg 37,Room 3068A, Bethesda, MD 20892 USA.
EM Curtis_Harris@nih.gov
OI Ryan, Brid/0000-0003-0038-131X
FU National Institute of Health, NCI-CCR
FX This work was supported by the Intramural Research Program of the
National Institute of Health, NCI-CCR.
NR 164
TC 573
Z9 597
U1 6
U2 72
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-175X
J9 NAT REV CANCER
JI Nat. Rev. Cancer
PD JUN
PY 2010
VL 10
IS 6
BP 389
EP 402
DI 10.1038/nrc2867
PG 14
WC Oncology
SC Oncology
GA 600YI
UT WOS:000278024500010
PM 20495573
ER
PT J
AU Subramanian, J
Simon, R
AF Subramanian, Jyothi
Simon, Richard
TI What should physicians look for in evaluating prognostic gene-expression
signatures?
SO NATURE REVIEWS CLINICAL ONCOLOGY
LA English
DT Review
ID CELL LUNG-CANCER; BREAST-CANCER; TUMOR-MARKERS; PREDICTIVE BIOMARKERS;
CLINICAL-ONCOLOGY; COLORECTAL-CANCER; AMERICAN-SOCIETY; MICROARRAY DATA;
TRIAL; PROFILES
AB Most cancer treatments benefit only a minority of patients. This has led to a widespread interest in the identification of gene-expression-based prognostic signatures. Well-developed and validated genomic signatures can lead to personalized treatment decisions resulting in improved patient management. However, the pace of acceptance of these signatures in clinical practice has been slow. This is because many of the signatures have been developed without clear focus on the intended clinical use, and proper independent validation studies establishing their medical utility have rarely been performed. The practicing physician and the patient are thus left in doubt about the reliability and medical utility of the signatures. We aim to provide guidance to physicians in critically evaluating published studies on prognostic gene-expression signatures so that they are better equipped to decide which signatures, if any, have sufficient merit for use, in conjunction with other factors in helping their patients to make good treatment decisions. A discussion of the lessons to be learned from the successful development of the Oncotype DX (R) genetic test for breast cancer is presented and contrasted with a review of the current status of prognostic gene-expression signatures in non-small-cell lung cancer.
C1 [Subramanian, Jyothi; Simon, Richard] NCI, Biometr Res Branch, Bethesda, MD 20892 USA.
RP Simon, R (reprint author), NCI, Biometr Res Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM rsimon@mail.nih.gov
NR 41
TC 42
Z9 43
U1 1
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4774
J9 NAT REV CLIN ONCOL
JI Nat. Rev. Clin. Oncol.
PD JUN
PY 2010
VL 7
IS 6
BP 327
EP 334
DI 10.1038/nrclinonc.2010.60
PG 8
WC Oncology
SC Oncology
GA 610FX
UT WOS:000278718200009
PM 20421890
ER
PT J
AU Kim, C
Paik, S
AF Kim, Chungyeul
Paik, Soonmyung
TI Gene-expression-based prognostic assays for breast cancer
SO NATURE REVIEWS CLINICAL ONCOLOGY
LA English
DT Review
ID PARAFFIN-EMBEDDED TISSUES; GENOMIC GRADE INDEX; MINDACT TRIAL;
DIAGNOSTIC-TEST; SIGNATURE; MICROARRAY; CHEMOTHERAPY; VALIDATION;
PREDICTORS; CARCINOMAS
AB Several gene-expression-based reference laboratory tests are now available for prognostication of patients diagnosed with breast cancer. For clinical oncologists, it is important to understand the clinical contexts for which these assays were developed in order to use them properly. This Review is aimed at providing a conceptual and technical overview of the steps involved in the development of gene-expression profiling-based prognostic assays. MammaPrint (R) and Oncotype DX (R), two widely utilized assays, are compared with respect to differences in the clinical contexts for their development, technologies used, and clinical utilities with the aim of providing a guide to clinical oncologists for utilization of these assays.
C1 [Kim, Chungyeul; Paik, Soonmyung] Natl Surg Adjuvant Breast & Bowel Project, Div Pathol, Pittsburgh, PA 15212 USA.
RP Paik, S (reprint author), Natl Surg Adjuvant Breast & Bowel Project, Div Pathol, Fed N Bldg,Suite 303, Pittsburgh, PA 15212 USA.
EM soon.paik@nsabp.org
OI kim, chungyeul/0000-0002-9636-5228; Paik, Soonmyung/0000-0001-9688-6480
NR 36
TC 87
Z9 90
U1 0
U2 16
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4774
J9 NAT REV CLIN ONCOL
JI Nat. Rev. Clin. Oncol.
PD JUN
PY 2010
VL 7
IS 6
BP 340
EP 347
DI 10.1038/nrclinonc.2010.61
PG 8
WC Oncology
SC Oncology
GA 610FX
UT WOS:000278718200011
PM 20440284
ER
PT J
AU Lee, EK
Kim, HH
Kuwano, Y
Abdelmohsen, K
Srikantan, S
Subaran, SS
Gleichmann, M
Mughal, MR
Martindale, JL
Yang, XL
Worley, PF
Mattson, MP
Gorospe, M
AF Lee, Eun Kyung
Kim, Hyeon Ho
Kuwano, Yuki
Abdelmohsen, Kotb
Srikantan, Subramanya
Subaran, Sarah S.
Gleichmann, Marc
Mughal, Mohamed R.
Martindale, Jennifer L.
Yang, Xiaoling
Worley, Paul F.
Mattson, Mark P.
Gorospe, Myriam
TI hnRNP C promotes APP translation by competing with FMRP for APP mRNA
recruitment to P bodies
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Article
ID AMYLOID PRECURSOR-PROTEIN; X MENTAL-RETARDATION; ALZHEIMERS-DISEASE;
CYTOPLASMIC FOCI; BINDING PROTEINS; HUMAN-CELLS; EXPRESSION; GENE; HUR;
PHOSPHORYLATION
AB Amyloid precursor protein (APP) regulates neuronal synapse function, and its cleavage product Ab is linked to Alzheimer's disease. Here, we present evidence that the RNA-binding proteins (RBPs) heterogeneous nuclear ribonucleoprotein (hnRNP) C and fragile X mental retardation protein (FMRP) associate with the same APP mRNA coding region element, and they influence APP translation competitively and in opposite directions. Silencing hnRNP C increased FMRP binding to APP mRNA and repressed APP translation, whereas silencing FMRP enhanced hnRNP C binding and promoted translation. Repression of APP translation was linked to colocalization of FMRP and tagged APP RNA within processing bodies; this colocalization was abrogated by hnRNP C overexpression or FMRP silencing. Our findings indicate that FMRP represses translation by recruiting APP mRNA to processing bodies, whereas hnRNP C promotes APP translation by displacing FMRP, thereby relieving the translational block.
C1 [Lee, Eun Kyung; Kim, Hyeon Ho; Kuwano, Yuki; Abdelmohsen, Kotb; Srikantan, Subramanya; Martindale, Jennifer L.; Yang, Xiaoling; Gorospe, Myriam] NIA, Cellular & Mol Biol Lab, Intramural Res Program, US NIH, Baltimore, MD 21224 USA.
[Subaran, Sarah S.] NIA, Confocal Imaging Facil, Res Resources Branch, Intramural Res Program,US NIH, Baltimore, MD 21224 USA.
[Gleichmann, Marc; Mughal, Mohamed R.; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, US NIH, Baltimore, MD 21224 USA.
[Worley, Paul F.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
RP Gorospe, M (reprint author), NIA, Cellular & Mol Biol Lab, Intramural Res Program, US NIH, Baltimore, MD 21224 USA.
EM myriam-gorospe@nih.gov
RI Mattson, Mark/F-6038-2012;
OI srikantan, subramanya/0000-0003-1810-6519; abdelmohsen,
Kotb/0000-0001-6240-5810
FU National Institute on Aging, US National Institutes of Health;
[DA00266]
FX We thank F.E. Indig and M. H. Dehoff for assistance with experiments.
This research was supported by the National Institute on
Aging-Intramural Research Program, US National Institutes of Health.
P.F.W. is suppported by DA00266.
NR 48
TC 67
Z9 67
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9985
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD JUN
PY 2010
VL 17
IS 6
BP 732
EP U106
DI 10.1038/nsmb.1815
PG 9
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 606AU
UT WOS:000278393400018
PM 20473314
ER
PT J
AU Jin, J
Bai, L
Johnson, DS
Fulbright, RM
Kireeva, ML
Kashlev, M
Wang, MD
AF Jin, Jing
Bai, Lu
Johnson, Daniel S.
Fulbright, Robert M.
Kireeva, Maria L.
Kashlev, Mikhail
Wang, Michelle D.
TI Synergistic action of RNA polymerases in overcoming the nucleosomal
barrier
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Article
ID TRANSCRIPTION ELONGATION COMPLEX; II ELONGATION; IN-VIVO;
ESCHERICHIA-COLI; DNA INTERACTIONS; HIGH-AFFINITY; FACTOR TFIIS;
RESOLUTION; MOLECULES; PROMOTER
AB During gene expression, RNA polymerase (RNAP) encounters a major barrier at a nucleosome and yet must access the nucleosomal DNA. Previous in vivo evidence has suggested that multiple RNAPs might increase transcription efficiency through nucleosomes. Here we have quantitatively investigated this hypothesis using Escherichia coli RNAP as a model system by directly monitoring its location on the DNA via a single-molecule DNA-unzipping technique. When an RNAP encountered a nucleosome, it paused with a distinctive 10-base pair periodicity and backtracked by similar to 10-15 base pairs. When two RNAPs elongate in close proximity, the trailing RNAP apparently assists in the leading RNAP's elongation, reducing its backtracking and enhancing its transcription through a nucleosome by a factor of 5. Taken together, our data indicate that histone-DNA interactions dictate RNAP pausing behavior, and alleviation of nucleosome-induced backtracking by multiple polymerases may prove to be a mechanism for overcoming the nucleosomal barrier in vivo.
C1 [Jin, Jing; Bai, Lu; Johnson, Daniel S.; Fulbright, Robert M.; Wang, Michelle D.] Cornell Univ, Dept Phys, Atom & Solid State Phys Lab, Ithaca, NY 14853 USA.
[Jin, Jing; Wang, Michelle D.] Cornell Univ, Howard Hughes Med Inst, Ithaca, NY USA.
[Kireeva, Maria L.; Kashlev, Mikhail] NCI, Ctr Canc Res, Frederick, MD 21701 USA.
RP Wang, MD (reprint author), Cornell Univ, Dept Phys, Atom & Solid State Phys Lab, Ithaca, NY 14853 USA.
EM mdw17@cornell.edu
FU US National Institutes of Health [GM059849]; US National Science
Foundation [MCB-0820293]; Keck Foundation; Cornell Nanobiotechnology
Center
FX We thank members of the Wang laboratory for critical reading of the
manuscript, J. Widom (Northwestern University) for the plasmid
containing the 601 NPE and the J. Roberts laboratory (Cornell
University) for help with the phosphorescence gel scanner. M.D.W. wishes
to acknowledge support from the US National Institutes of Health
(GM059849), the US National Science Foundation (MCB-0820293), the Keck
Foundation Distinguished Young Scholar in Medical Research Award and the
Cornell Nanobiotechnology Center.
NR 57
TC 67
Z9 67
U1 0
U2 11
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9985
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD JUN
PY 2010
VL 17
IS 6
BP 745
EP U122
DI 10.1038/nsmb.1798
PG 9
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 606AU
UT WOS:000278393400020
PM 20453861
ER
PT J
AU Campen, CJ
Kranick, SM
Kasner, SE
Kessler, S
Ichord, R
Beslow, LA
Smith, SE
Licht, DJ
Fisher, MJ
AF Campen, C. J.
Kranick, S. M.
Kasner, S. E.
Kessler, S.
Ichord, R.
Beslow, L. A.
Smith, S. E.
Licht, D. J.
Fisher, M. J.
TI LATE NEURO VASCULAR EVENTS IN PEDIATRIC BRAIN TUMOR PATIENTS
SO NEURO-ONCOLOGY
LA English
DT Meeting Abstract
CT 14th International Symposium on Pediatric Neuro-Oncology
CY JUN 20-23, 2010
CL Vienna, AUSTRIA
C1 [Campen, C. J.] Stanford Univ, Stanford, CA 94305 USA.
[Kranick, S. M.] Natl Inst Hlth, Washington, DC USA.
[Kasner, S. E.] Univ Penn, Philadelphia, PA 19104 USA.
[Kessler, S.; Ichord, R.; Beslow, L. A.; Smith, S. E.; Licht, D. J.; Fisher, M. J.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
RI Kasner, Scott/C-6109-2011; Licht, Daniel/I-3370-2013
OI Licht, Daniel/0000-0002-4080-843X
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD JUN
PY 2010
VL 12
IS 6
BP II40
EP II41
PG 2
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 611LW
UT WOS:000278817700185
ER
PT J
AU Hipp, SJ
Steffen-Smith, E
Hammond, D
Shih, JH
Bent, R
Warren, KE
AF Hipp, S. J.
Steffen-Smith, E.
Hammond, D.
Shih, J. H.
Bent, R.
Warren, K. E.
TI PREDICTING OUTCOME OF CHILDREN WITH DIPG USING MULTIPARAMETRIC IMAGING
SO NEURO-ONCOLOGY
LA English
DT Meeting Abstract
CT 14th International Symposium on Pediatric Neuro-Oncology
CY JUN 20-23, 2010
CL Vienna, AUSTRIA
C1 [Hipp, S. J.; Steffen-Smith, E.; Shih, J. H.; Bent, R.; Warren, K. E.] Natl Canc Inst, Bethesda, MD USA.
[Hipp, S. J.] Walter Reed Army Med Ctr, Washington, DC 20307 USA.
[Hammond, D.] Natl Inst Hlth, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD JUN
PY 2010
VL 12
IS 6
BP II9
EP II9
PG 1
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 611LW
UT WOS:000278817700046
ER
PT J
AU Kim, A
Dombi, E
Tepas, K
Fox, E
Balis, FM
Korf, B
Widemann, BC
AF Kim, A.
Dombi, E.
Tepas, K.
Fox, E.
Balis, F. M.
Korf, B.
Widemann, B. C.
TI PHASE I TRIAL OF SORAFENIB IN CHILDREN WITH NEUROFIBROMATOSIS TYPE I
(NF1) AND INOPERABLE PLEXIFORM NEUROFIBROMAS (PN)
SO NEURO-ONCOLOGY
LA English
DT Meeting Abstract
CT 14th International Symposium on Pediatric Neuro-Oncology
CY JUN 20-23, 2010
CL Vienna, AUSTRIA
C1 [Kim, A.; Dombi, E.; Tepas, K.; Widemann, B. C.] Natl Canc Inst, Bethesda, MD USA.
[Fox, E.; Balis, F. M.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Korf, B.] Univ Alabama, Birmingham, AL USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD JUN
PY 2010
VL 12
IS 6
BP II42
EP II42
PG 1
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 611LW
UT WOS:000278817700192
ER
PT J
AU Steffen-Smith, EA
Sarlls, JE
Pierpaoli, C
Warren, KE
AF Steffen-Smith, E. A.
Sarlls, J. E.
Pierpaoli, C.
Warren, K. E.
TI DIFFUSION TENSOR IMAGING (DTI) IN CHILDREN WITH DIFFUSE INTRINSIC
PONTINE GLIOMA (DIPG)
SO NEURO-ONCOLOGY
LA English
DT Meeting Abstract
CT 14th International Symposium on Pediatric Neuro-Oncology
CY JUN 20-23, 2010
CL Vienna, AUSTRIA
C1 [Steffen-Smith, E. A.; Warren, K. E.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Sarlls, J. E.; Pierpaoli, C.] NICHD, Program Pediat Imaging & Tissue Sci, Bethesda, MD USA.
RI Pierpaoli, Carlo/E-1672-2011
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD JUN
PY 2010
VL 12
IS 6
BP II33
EP II33
PG 1
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 611LW
UT WOS:000278817700152
ER
PT J
AU Warren, K
Bent, R
Wolters, P
Shih, J
Prager, A
Camphausen, K
AF Warren, K.
Bent, R.
Wolters, P.
Shih, J.
Prager, A.
Camphausen, K.
TI A PHASE II STUDY OF PEGYLATED INTERFERON ALFA-2B (PEG-INTRON (TM)) IN
CHILDREN WITH DIFFUSE INTRINSIC PONTINE GLIOMAS (DI PG)
SO NEURO-ONCOLOGY
LA English
DT Meeting Abstract
CT 14th International Symposium on Pediatric Neuro-Oncology
CY JUN 20-23, 2010
CL Vienna, AUSTRIA
C1 [Warren, K.; Bent, R.; Wolters, P.; Shih, J.; Prager, A.; Camphausen, K.] Natl Canc Inst, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD JUN
PY 2010
VL 12
IS 6
BP II9
EP II9
PG 1
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 611LW
UT WOS:000278817700048
ER
PT J
AU Weiss, B
Widemann, BC
Cantor, A
Perentesis, J
Vinks, A
Ullrich, N
Gutmann, D
Korp, B
Packer, R
Fisher, MJ
AF Weiss, B.
Widemann, B. C.
Cantor, A.
Perentesis, J.
Vinks, A.
Ullrich, N.
Gutmann, D.
Korp, B.
Packer, R.
Fisher, M. J.
TI TOLERABILITY OF THE MTOR INHIBITOR SIROLIMUS IN A PHASE II STUDY FOR
NEUROFIBROMATOSIS TYPE 1 (NF1)-ASSOCIATED PLEXIFORM NEUROFIBROMAS: A
NEUROFIBROMATOSIS CONSORTIUM STUDY
SO NEURO-ONCOLOGY
LA English
DT Meeting Abstract
CT 14th International Symposium on Pediatric Neuro-Oncology
CY JUN 20-23, 2010
CL Vienna, AUSTRIA
C1 [Weiss, B.; Perentesis, J.; Vinks, A.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA.
[Widemann, B. C.] NIH, Bethesda, MD 20892 USA.
[Cantor, A.; Korp, B.] Univ Alabama, Sch Med, Birmingham, AL USA.
[Ullrich, N.] Childrens Hosp Boston, Boston, MA USA.
[Gutmann, D.] Washington Univ, Sch Med, St Louis, MO USA.
[Packer, R.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Fisher, M. J.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD JUN
PY 2010
VL 12
IS 6
BP II85
EP II85
PG 1
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 611LW
UT WOS:000278817700388
ER
PT J
AU Weiss, B
Fisher, MJ
Dombi, E
Cantor, A
Vinks, A
Korf, B
Schorry, E
Gutmann, D
Packer, R
Widemann, BC
AF Weiss, B.
Fisher, M. J.
Dombi, E.
Cantor, A.
Vinks, A.
Korf, B.
Schorry, E.
Gutmann, D.
Packer, R.
Widemann, B. C.
TI PHASE II STUDY OF THE MTOR INHIBITOR SIROLIMUS FOR NON-PROGRESSIVE
NF1-ASSOCIATED PLEXIFORM NEUROFIBROMAS: A NEUROFIBROMATOSIS CONSORTIUM
STUDY
SO NEURO-ONCOLOGY
LA English
DT Meeting Abstract
CT 14th International Symposium on Pediatric Neuro-Oncology
CY JUN 20-23, 2010
CL Vienna, AUSTRIA
C1 [Weiss, B.; Vinks, A.; Schorry, E.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA.
[Fisher, M. J.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Dombi, E.; Widemann, B. C.] Natl Inst Hlth, Bethesda, MD USA.
[Cantor, A.; Korf, B.] Univ Alabama, Med Sch Birmingham, Birmingham, AL USA.
[Gutmann, D.] Washington Univ, Sch Med, St Louis, MO USA.
[Packer, R.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD JUN
PY 2010
VL 12
IS 6
BP II43
EP II43
PG 1
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 611LW
UT WOS:000278817700194
ER
PT J
AU Corneveaux, JJ
Liang, WS
Reiman, EM
Webster, JA
Myers, AJ
Zismann, VL
Joshipura, KD
Pearson, JV
Hu-Lince, D
Craig, DW
Coon, KD
Dunckley, T
Bandy, D
Lee, W
Chen, KW
Beach, TG
Mastroeni, D
Grover, A
Ravid, R
Sando, SB
Aasly, JO
Heun, R
Jessen, F
Kolsch, H
Rogers, J
Hutton, ML
Melquist, S
Petersen, RC
Alexander, GE
Caselli, RJ
Papassotiropoulos, A
Stephan, DA
Huentelman, MJ
AF Corneveaux, Jason J.
Liang, Winnie S.
Reiman, Eric M.
Webster, Jennifer A.
Myers, Amanda J.
Zismann, Victoria L.
Joshipura, Keta D.
Pearson, John V.
Hu-Lince, Diane
Craig, David W.
Coon, Keith D.
Dunckley, Travis
Bandy, Daniel
Lee, Wendy
Chen, Kewei
Beach, Thomas G.
Mastroeni, Diego
Grover, Andrew
Ravid, Rivka
Sando, Sigrid B.
Aasly, Jan O.
Heun, Reinhard
Jessen, Frank
Koelsch, Heike
Rogers, Joseph
Hutton, Michael L.
Melquist, Stacey
Petersen, Ron C.
Alexander, Gene E.
Caselli, Richard J.
Papassotiropoulos, Andreas
Stephan, Dietrich A.
Huentelman, Matthew J.
TI Evidence for an association between KIBRA and late-onset Alzheimer's
disease
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Genetics; Imaging; Expression profiling; Memory
ID GENE-EXPRESSION; MEMORY PERFORMANCE; COGNITIVE RESERVE; ENTORHINAL
CORTEX; EPISODIC MEMORY; BRAIN; VARIANTS; DEMENTIA; ATROPHY; RISK
AB We recently reported evidence for an association between the individual variation in normal human episodic memory and a common variant of the KIBRA gene, KIBRA rs17070145 (T-allele). Since memory impairment is a cardinal clinical feature of Alzheimer's disease (AD), we investigated the possibility of an association between the KIBRA gene and AD using data from neuronal gene expression, brain imaging studies, and genetic association tests. KIBRA was significantly over-expressed and three of its four known binding partners under-expressed in AD-affected hippocampal, posterior cingulate and temporal cortex regions (P < 0.010, corrected) in a study of laser-capture microdissected neurons. Using positron emission tomography in a cohort of cognitively normal, late-middle-aged persons genotyped for KIBRA rs17070145, KIBRA T non-carriers exhibited lower glucose metabolism than did carriers in posterior cingulate and precuneus brain regions (P < 0.001, uncorrected). Lastly, non-carriers of the KIBRA rs17070145 T-allele had increased risk of late-onset AD in an association study of 702 neuropathologically verified expired subjects (P = 0.034; OR=1.29) and in a combined analysis of 1026 additional living and expired subjects (P=0.039; OR=1.26). Our findings suggest that KIBRA is associated with both individual variation in normal episodic memory and predisposition to AD. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Corneveaux, Jason J.; Liang, Winnie S.; Reiman, Eric M.; Webster, Jennifer A.; Zismann, Victoria L.; Joshipura, Keta D.; Pearson, John V.; Hu-Lince, Diane; Craig, David W.; Coon, Keith D.; Dunckley, Travis; Papassotiropoulos, Andreas; Stephan, Dietrich A.; Huentelman, Matthew J.] Translat Genom Res Inst TGen, Neurogenom Div, 445 N 5th St, Phoenix, AZ 85004 USA.
[Corneveaux, Jason J.; Liang, Winnie S.; Reiman, Eric M.; Webster, Jennifer A.; Zismann, Victoria L.; Joshipura, Keta D.; Pearson, John V.; Hu-Lince, Diane; Craig, David W.; Coon, Keith D.; Dunckley, Travis; Bandy, Daniel; Lee, Wendy; Chen, Kewei; Beach, Thomas G.; Mastroeni, Diego; Grover, Andrew; Rogers, Joseph; Alexander, Gene E.; Caselli, Richard J.; Stephan, Dietrich A.; Huentelman, Matthew J.] Arizona Alzheimers Consortium, Phoenix, AZ 85006 USA.
[Reiman, Eric M.; Bandy, Daniel; Lee, Wendy; Chen, Kewei] Banner Alzheimers Inst, Phoenix, AZ 85006 USA.
[Reiman, Eric M.] Univ Arizona, Dept Psychiat, Tucson, AZ 85724 USA.
[Myers, Amanda J.] Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33101 USA.
[Myers, Amanda J.] NIA, NIH, Neurogenet Lab, Bethesda, MD 20892 USA.
[Coon, Keith D.] St Josephs Hosp, Ctr Thorac Dis, Heart & Lung Inst, Phoenix, AZ 85013 USA.
[Beach, Thomas G.; Mastroeni, Diego; Grover, Andrew; Rogers, Joseph] Sun Hlth Res Inst, Sun City, AZ 85351 USA.
[Chen, Kewei] Univ Arizona, Dept Radiol, Tucson, AZ 85724 USA.
[Chen, Kewei] Arizona State Univ, Dept Math, Tempe, AZ 85287 USA.
[Ravid, Rivka] Netherlands Inst Neumsci, Dutch Royal Acad Arts & Sci, Amsterdam, Netherlands.
[Corneveaux, Jason J.; Liang, Winnie S.; Sando, Sigrid B.; Aasly, Jan O.] St Olavs Hosp, Dept Neurol, N-7006 Trondheim, Norway.
[Sando, Sigrid B.; Aasly, Jan O.] Norwegian Univ Sci & Technol, Dept Neurosci, NTNU, N-7491 Trondheim, Norway.
[Heun, Reinhard; Jessen, Frank; Koelsch, Heike] Univ Bonn, Dept Psychiat, D-5300 Bonn, Germany.
[Hutton, Michael L.; Melquist, Stacey] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA.
[Petersen, Ron C.] Mayo Clin, Dept Neurol, Rochester, MN 55905 USA.
[Alexander, Gene E.] Univ Arizona, Dept Psychol, Tucson, AZ 85721 USA.
[Alexander, Gene E.] Univ Arizona, Evelyn F McKnight Brain Inst, Tucson, AZ 85721 USA.
[Caselli, Richard J.] Mayo Clin, Dept Neurol, Scottsdale, AZ 85259 USA.
[Papassotiropoulos, Andreas] Univ Basel, Div Mol Psychol, Basel, Switzerland.
[Papassotiropoulos, Andreas] Univ Basel, Life Sci Training Facil, Basel, Switzerland.
RP Huentelman, MJ (reprint author), Translat Genom Res Inst TGen, Neurogenom Div, 445 N 5th St, Phoenix, AZ 85004 USA.
EM mhuentelman@tgen.org
RI Myers, Amanda/B-1796-2010; Jessen, Frank/E-7655-2012; Chen,
kewei/P-6304-2015; Pearson, John/F-2249-2011
OI Myers, Amanda/0000-0002-3100-9396; Chen, kewei/0000-0001-8497-3069;
Pearson, John/0000-0003-0904-4598
FU National Institute on Aging [P30 AG19610, RO1 AG023193, P50 AG 16574];
National Institute of Mental Health [R01 MH57899]; Arizona Alzheimer's
Consortium; Banner Alzheimer Foundation; Mayo Clinic Foundation;
National Alzheimer's Coordinating Center [U01 AG016976]; U01 AG016976),
the National Institutes of Health [R01 NS059873]; state of Arizona;
Johnnie B. Byrd Sr. Alzheimer's Disease and Research Institute; Swiss
National Science Foundation [PPOOB-68859]; Verum Foundation; Bisgrove
charitable donation; NIH Neuroscience Blueprint [U24NS051872]; ENDGAME
Consortium [UOIHL084744]; National Institute on Aging grant to Carl
Cotman (University of California, Irvine) [P50 AG23173]; NIH NINDS
[NS059873A]
FX We would like to thank Christopher B. Heward of Kronos Life Sciences
Laboratories for support on the first AD association study. This study
was also funded by the National Institute on Aging (Arizona Alzheimer's
Disease Center P30 AG19610, RO1 AG023193, Mayo Clinic Alzheimer's
Disease Center P50 AG 16574 and Intramural Research Program, P30 AG19610
to E.M.R.), the National Institute of Mental Health (R01 MH57899 to
E.M.R.), the Arizona Alzheimer's Consortium (Arizona Department of
Health Services to E.M.R.), the Banner Alzheimer Foundation (to E.M.R.),
the Mayo Clinic Foundation (to R.J.C.), the National Alzheimer's
Coordinating Center (U01 AG016976), the National Institutes of Health
(R01 NS059873 to M.J.H.) and the state of Arizona. We thank our research
volunteers and their families for their generous participation and Drs.
Creighton Phelps, Marcelle Morrison-Bogorad, Marilyn Miller, and Walter
Kukull for their assistance in the acquisition of tissue samples and
data, and directors, pathologists, and technologists from the following
ADCs and brain banks: Lucia Sue (Sun Health Research Institute and
Arizona Alzheimer's Disease Center); Ruth Seemann and Dan Brady
(National Institute on Aging); Juan C. Troncoso and Olga Pletnikova
(John Hopkins, P50 AG05146); Harry Vinters and Justine Pomakian
(University of California, Los Angeles, P50 AG16570); Christine M.
Hulette (The Kathleen Price Bryan Brain Bank, Duke University Medical
Center, P50 AG05128, ROI NS39764, ROI MH60451, and GlaxoSmithKline);
Dilcran Horoupian, Ahmad Salehi (Stanford University, P30 AG17824); Jean
Paul Vonsattel (New York Brain Bank, Taub Institute, Columbia
University, P50 AG08702); E. Tessa Hedley-Whyte, Karlotta Fitch
(Massachusetts General Hospital, P50 AG05134); Roger Albin, Lisa Bain,
and Eszter Gombosi (University of Michigan, P50 AG08671); William
Markesbery, Sonya Anderson (University of Kentucky, P50 AG05144); Dennis
W. Dickson and Natalie Thomas (Mayo Clinic, Jacksonville, P50 AG16574
and P50 AG2571 1); Carol A. Miller, Jenny Tang, and Dimitri Diaz
(University of Southern California, P50 AG05142); Dan McKeel, John C.
Morris, Eugene Johnson, Jr., Virginia Buckles, and Deborah Carter
(Washington University, St Louis, P50 AG 05681); Thomas Montine and
Aimee Schantz (University of Washington, P50 AG05136); John Q.
Trojanowski, Virginia M. Lee, Vivianna Van Deerlin, and Terry Schuck
(University of Pennsylvania); Ann C. McKee and Carol Kubilus (Boston
University, P30 AG13846); Bruce H. Wainer and Marla Gearing (Emory
University, AG025688); Charles L. White, Ill, Roger Rosenberg, Marilyn
Howell, and Joan Reisch (University of Texas, Southwestern Medical
School, P30-AG12300); William Ellis and Mary Ann Jarvis, (University of
California, Davis, P30 AG AG01542); David A. Bennett, Julie A.
Schneider, Karen Skish, and Wayne T. Longman (Rush University Medical
Center, P30 AG10161); Deborah C. Mash, Margaret J. Basile, and Mitsuko
Tanaka University of Miami/NPF Brain Endowment Bank); and Nick Lehmans
(Translational Genomics Research Institute). Additional support was
provided by the Johnnie B. Byrd Sr. Alzheimer's Disease and Research
Institute, the Swiss National Science Foundation (PPOOB-68859), the
Verum Foundation, the Bisgrove charitable donation, the NIH Neuroscience
Blueprint (U24NS051872), the ENDGAME Consortium (UOIHL084744), a
National Institute on Aging grant to Carl Cotman (University of
California, Irvine, P50 AG23173) and the state of Arizona. NIH NINDS
grant #NS059873A as well as funding from Science Foundation Arizona.
NR 31
TC 50
Z9 51
U1 3
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD JUN
PY 2010
VL 31
IS 6
BP 901
EP 909
DI 10.1016/j.neurobiolaging.2008.07.014
PG 9
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 590RZ
UT WOS:000277246400002
PM 18789830
ER
PT J
AU Jo, DG
Arumugam, TV
Woo, HN
Park, JS
Tang, SC
Mughal, M
Hyun, DH
Park, JH
Choi, YH
Gwon, AR
Camandola, S
Cheng, AW
Cai, HB
Song, WH
Markesbery, WR
Mattson, MP
AF Jo, Dong-Gyu
Arumugam, Thiruma V.
Woo, Ha-Na
Park, Jong-Sung
Tang, Sung-Chun
Mughal, Mohamed
Hyun, Dong-Hoon
Park, Jun-Hyung
Choi, Yun-Hyung
Gwon, A-Ryeong
Camandola, Simonetta
Cheng, Aiwu
Cai, Huaibin
Song, Weihong
Markesbery, William R.
Mattson, Mark P.
TI Evidence that gamma-secretase mediates oxidative stress-induced
beta-secretase expression in Alzheimer's disease
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE beta-Secretase; Alzheimer's disease; Oxidative stress; gamma-Secretase
ID AMYLOID PRECURSOR PROTEIN; DEPENDENT TRANSCRIPTIONAL CONTROL; DEGRADING
ENZYME NEPRILYSIN; LIPID-PEROXIDATION; A-BETA; INTRACELLULAR DOMAINS;
GENE-EXPRESSION; NEURONAL DEATH; FREE-RADICALS; BACE1
AB B-Secretase (BACE I), an enzyme responsible for the production of amyloid p-peptide (AB), is increased by oxidative stress and is elevated in the brains of patients with sporadic Alzheimer's disease (AD). Here, we show that oxidative stress fails to induce BACE I expression in presenilin-I (gamma-secretase)-deficient cells and in normal cells treated with gamma-secretase inhibitors. Oxidative stress-induced B-secretase activity and sAPPB levels were suppressed by gamma-secretase inhibitors. Levels of and beta-secretase activities were greater in brain tissue samples from AD patients compared to non-demented control subjects, and the elevated BACE I level in the brains of 3xTgAD mice was reduced by treatment with a gamma-secretase inhilitor. Our findings suggest that gamma-secretase mediates oxidative stress-induced expression of BACE I resulting in excessive AB production in AD. Published by Elsevier Inc.
C1 [Jo, Dong-Gyu; Arumugam, Thiruma V.; Tang, Sung-Chun; Mughal, Mohamed; Hyun, Dong-Hoon; Camandola, Simonetta; Cheng, Aiwu; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
[Jo, Dong-Gyu; Woo, Ha-Na; Park, Jong-Sung; Park, Jun-Hyung; Choi, Yun-Hyung; Gwon, A-Ryeong] Sungkyunkwan Univ, Coll Pharm, Suwon, South Korea.
[Tang, Sung-Chun] Natl Taiwan Univ Hosp, Stroke Ctr, Dept Neurol, Taipei, Taiwan.
[Hyun, Dong-Hoon] Ewha Womans Univ, Div Mol Life Sci, Seoul, South Korea.
[Cai, Huaibin] Univ British Columbia, Dept Psychiat, Brain Res Ctr, Vancouver, BC V5Z 1M9, Canada.
[Cai, Huaibin] Univ British Columbia, Grad Program Neurosci, Vancouver, BC V5Z 1M9, Canada.
[Song, Weihong] NIA, Neurogenet Lab, Bethesda, MD 20892 USA.
[Markesbery, William R.] Univ Kentucky, Sanders Brown Res Ctr Aging, Lexington, KY USA.
[Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM mattsonm@grc.nia.nih.gov
RI Arumugam, Thiruma/B-4898-2011; Mattson, Mark/F-6038-2012; Cai,
Huaibin/H-3359-2013;
OI Cai, Huaibin/0000-0002-8596-6108; Tang, Sung-Chun/0000-0003-3731-5973
FU National Institute on Aging, NIH; Korea Research Foundation; MOEHRD
[KRF-2007-313-000526]
FX This research was supported by the Intramural Research Program of the
National Institute on Aging, NIH, and by a Korea Research Foundation
Grant to D.-G.J. (MOEHRD, Basic Research Promotion Fund)
(KRF-2007-313-000526).
NR 30
TC 41
Z9 44
U1 0
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD JUN
PY 2010
VL 31
IS 6
BP 917
EP 925
DI 10.1016/j.neurobiolaging.2008.07.003
PG 9
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 590RZ
UT WOS:000277246400004
PM 18687504
ER
PT J
AU Gredilla, R
Garm, C
Holm, R
Bohr, VA
Stevnsner, T
AF Gredilla, Ricardo
Garm, Christian
Holm, Rikke
Bohr, Vilhelm A.
Stevnsner, Tinna
TI Differential age-related changes in mitochondrial DNA repair activities
in mouse brain regions
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE DNA repair; Base excision repair; Mitochondria; Aging; Brain
ID BASE-EXCISION-REPAIR; OXIDATIVE DAMAGE; PARKINSONS-DISEASE;
ALZHEIMERS-DISEASE; NITRIC-OXIDE; NUCLEAR-DNA; RAT-BRAIN; LIFE-SPAN;
MUTATIONS; MICE
AB Aging in the brain is characterized by increased susceptibility to neuronal loss and functional decline, and mitochondrial DNA (mtDNA) mutations are thought to play an important role in these processes. Due to the proximity of mtDNA to the main sites of mitochondrial free radical generation, oxidative stress is a major source of DNA mutations in mitochondria. The base excision repair (B ER) pathway removes oxidative lesions from mtDNA, thereby constituting an important mechanism to avoid accumulation of mtDNA mutations. The complexity of the brain implies that exposure and defence against oxidative stress varies among brain regions and hence some regions may be particularly prone to accumulation of mtDNA damages. In the current study we investigated the efficiency of the BER pathway throughout the murine lifespan in mitochondria from cortex and hippocampus, regions that are central in mammalian cognition, and which are severely affected during aging and in neurodegenerative diseases. A regional specific regulation of mitochondrial DNA repair activities was observed with aging. In cortical mitochondria, DNA glycosylase activities peaked at middle-age followed by a significant drop at old age. However, only minor changes were observed in hippocampal mitochondria during the whole lifespan of the animals. Furthermore. DNA glycosylase activities were lower in hippocampal than in cortical mitochondria. Mitochondrial AP endonuclease activity increased in old animals in both brain regions. Our data suggest an important regional specific regulation of mitochondrial BER. during aging. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Gredilla, Ricardo; Garm, Christian; Holm, Rikke; Stevnsner, Tinna] Univ Aarhus, Danish Ctr Mol Gerontol, DK-8000 Aarhus C, Denmark.
[Gredilla, Ricardo; Garm, Christian; Holm, Rikke; Stevnsner, Tinna] Univ Aarhus, Dept Mol Biol, Danish Aging Res Ctr, DK-8000 Aarhus C, Denmark.
[Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
RP Stevnsner, T (reprint author), Univ Aarhus, Danish Ctr Mol Gerontol, CF Moellers Alle 1130, DK-8000 Aarhus C, Denmark.
EM tvs@mb.au.dk
FU European Commission [LSHM-CT-2004-512020]; Lundbeck Foundation
[4-55951-95094019]; Danish Cancer Association; National Institute on
Aging, NIH
FX This research was supported by grants from the European Commission
(LSHM-CT-2004-512020) and Lundbeck Foundation (4-55951-95094019) to TS.
CG and RH were supported by the Danish Cancer Association. This research
was also partially supported by funds from the intramural program of the
National Institute on Aging, NIH. We thank Birija S. Patro and Rikke F.
Frohlich for critical reading of the manuscript.
NR 59
TC 28
Z9 28
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD JUN
PY 2010
VL 31
IS 6
BP 993
EP 1002
DI 10.1016/j.neurobiolaging.2008.07.004
PG 10
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 590RZ
UT WOS:000277246400010
PM 18701195
ER
PT J
AU Hobaika, Z
Zargarian, L
Maroun, RG
Mauffret, O
Burke, TR
Fermandjian, S
AF Hobaika, Z.
Zargarian, L.
Maroun, R. G.
Mauffret, O.
Burke, T. R., Jr.
Fermandjian, S.
TI HIV-1 Integrase and Virus and Cell DNAs: Complex Formation and
Perturbation by Inhibitors of Integration
SO NEUROCHEMICAL RESEARCH
LA English
DT Article; Proceedings Paper
CT Conference in honor of Armen Galoyan for his 80th Birthday
CY OCT, 2009
CL Yerevan, ARMENIA
DE HIV-1; Integrase; DNA; Interactions; Inhibitors
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CRYSTAL-STRUCTURE; VIRAL-DNA; CATALYTIC
DOMAIN; TYPE-1 INTEGRASE; ACTIVE-SITE; IN-VITRO; RESIDUES; BINDING;
RESISTANCE
AB HIV-1 integrase (IN) catalyzes integration of viral DNA into cell DNA through 3'-processing of viral DNA and strand transfer reactions. To learn on binding of IN to DNAs and IN inhibition we applied spectroscopy (circular dichroism, fluorescence) in a simplified model consisting in a peptide analogue (K156) of alpha 4 helix involved in recognition of viral and cell DNA; an oligonucleotide corresponding to the U5' LTR DNA end; and an inhibitor (TB11) of the diketo acid (DKA) family. Results extrapolated to IN show that: the enzyme binds viral DNA with high affinity and specificity, but cell DNA with low affinity and specificity; the affinity of TB11 for IN is high enough to impair the binding of IN to cell DNA, but not to viral DNA. This explains why TB11 is an inhibitor of strand transfer but not of 3'-processing. These results can help in the search of new IN inhibitors.
C1 [Hobaika, Z.; Zargarian, L.; Mauffret, O.; Fermandjian, S.] Ecole Normale Super, Lab Biotechnol & Pharmacol Genet Appl, UMR 8113, CNRS, F-94235 Cachan, France.
[Maroun, R. G.] Univ St Joseph, Fac Sci, Dept Sci Vie & Terre, CST Mar Roukos, Beirut, Lebanon.
[Burke, T. R., Jr.] NCI, Med Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
RP Fermandjian, S (reprint author), Ecole Normale Super, Lab Biotechnol & Pharmacol Genet Appl, UMR 8113, CNRS, 61 Ave President Wilson, F-94235 Cachan, France.
EM serge.fermandjian@lbpa.ens-cachan.fr
RI Burke, Terrence/N-2601-2014
NR 27
TC 3
Z9 3
U1 0
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-3190
J9 NEUROCHEM RES
JI Neurochem. Res.
PD JUN
PY 2010
VL 35
IS 6
SI SI
BP 888
EP 893
DI 10.1007/s11064-009-0098-2
PG 6
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 600ZQ
UT WOS:000278028100007
PM 19937113
ER
PT J
AU Shen, W
Durum, SK
AF Shen, Wei
Durum, Scott K.
TI Synergy of IL-23 and Th17 Cytokines: New Light on Inflammatory Bowel
Disease
SO NEUROCHEMICAL RESEARCH
LA English
DT Article; Proceedings Paper
CT Conference in honor of Armen Galoyan for his 80th Birthday
CY OCT, 2009
CL Yerevan, ARMENIA
DE Inflammatory bowel disease (IBD); IL-23; IL-17A; IL-17F; IL-22
ID ROR-GAMMA-T; MEDIATED INTESTINAL INFLAMMATION; CELL-DEPENDENT COLITIS;
GROWTH-FACTOR-BETA; AUTOIMMUNE ENCEPHALOMYELITIS; HETERODIMERIC
CYTOKINE; CUTTING EDGE; TGF-BETA; RECEPTOR; DIFFERENTIATION
AB Inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis, involve an interplay between host genetics and environmental factors including intestinal microbiota. Animal models of IBD have indicated that chronic inflammation can result from over-production of inflammatory responses or deficiencies in key negative regulatory pathways. Recent research advances in both T-helper 1 (Th1) and T-helper 17 (Th17) effect responses have offered new insights on the induction and regulation of mucosal immunity which is linked to the development of IBD. Th17 cytokines, such as IL-17 and IL-22, in combination with IL-23, play crucial roles in intestinal protection and homeostasis. IL-23 is expressed in gut mucosa and tends to orchestrate T-cell-independent pathways of intestinal inflammation as well as T cell dependent pathways mediated by cytokines produced by Th1 and Th17 cells. Th17 cells, generally found to be proinflammatory, have specific functions in host defense against infection by recruiting neutrophils and macrophages to infected tissues. Here we will review emerging data on those cytokines and their related regulatory networks that appear to govern the complex development of chronic intestinal inflammation; we will focus on how IL-23 and Th17 cytokines act coordinately to influence the balance between tolerance and immunity in the intestine.
C1 [Shen, Wei; Durum, Scott K.] NCI, Mol Immunoregulat Lab, Canc Inflammat Program, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
RP Durum, SK (reprint author), NCI, Mol Immunoregulat Lab, Canc Inflammat Program, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
EM durums@mail.ncifcrf.gov
NR 48
TC 42
Z9 44
U1 2
U2 5
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-3190
J9 NEUROCHEM RES
JI Neurochem. Res.
PD JUN
PY 2010
VL 35
IS 6
SI SI
BP 940
EP 946
DI 10.1007/s11064-009-0091-9
PG 7
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 600ZQ
UT WOS:000278028100015
PM 19915978
ER
PT J
AU Volkow, ND
Tomasi, D
Wang, GJ
Fowler, JS
Telang, F
Wang, RL
Alexoff, D
Logan, J
Wong, C
Pradhan, K
Caparelli, EC
Ma, YM
Jayne, M
AF Volkow, Nora D.
Tomasi, Dardo
Wang, Gene-Jack
Fowler, Joanna S.
Telang, Frank
Wang, Ruiliang
Alexoff, Dave
Logan, Jean
Wong, Christopher
Pradhan, Kith
Caparelli, Elisabeth C.
Ma, Yeming
Jayne, Millard
TI Effects of low-field magnetic stimulation on brain glucose metabolism
SO NEUROIMAGE
LA English
DT Article
DE Brain imaging; Echo planar; Brain glucose metabolism; fMRI
ID POSITRON-EMISSION-TOMOGRAPHY; CRANIAL ELECTROTHERAPY STIMULATION;
ELECTROCONVULSIVE-THERAPY; GRADIENT COIL; LOW-FREQUENCY; DEPRESSION;
CORTEX; MRI; FUTURE; INHIBITION
AB Echo planar imaging (EPI), the gold standard technique for functional MRI (fMRI), is based on fast magnetic field gradient switching. These time-varying magnetic fields induce electric (E) fields in the brain that could influence neuronal activity; but this has not been tested. Here we assessed the effects of EPI on brain glucose metabolism (marker of brain function) using PET and 18F 2-fluoro-2-deoxy-D-glucose ((18)FDG). Fifteen healthy subjects were in a 4T magnet during the (18)FDG uptake period twice: with (ON) and without (OFF) EPI gradients pulses along the z-axis (G(z): 23 mT/m; 250 mu s rise-time; 920 Hz). The E-field from these EPI pulses is non-homogeneous, increasing linearly from the gradient's isocenter (radial and z directions), which allowed us to assess the correlation between local strength of the E-field and the regional metabolic differences between ON and OFF sessions. Metabolic images were normalized to metabolic activity in the plane positioned at the gradient's isocenter where E = 0 for both ON and OFF conditions. Statistical parametric analyses used to identify regions that differed between ON versus OFF (p<0.05, corrected) showed that the relative metabolism was lower in areas at the poles of the brain (inferior occipital and frontal and superior parietal cortices) for ON than for OFF, which was also documented with individual region of interest analysis. Moreover the magnitude of the metabolic decrements was significantly correlated with the estimated strength of E (r = 0.68, p<0.0001): the stronger the E-field the larger the decreases. However, we did not detect differences between ON versus OFF conditions on mood ratings nor on absolute whole brain metabolism. This data provides preliminary evidence that EPI sequences may affect neuronal activity and merits further investigation. Published by Elsevier Inc.
C1 [Volkow, Nora D.] NIDA, Bethesda, MD 20892 USA.
[Volkow, Nora D.; Tomasi, Dardo; Telang, Frank; Ma, Yeming; Jayne, Millard] NIAAA, Bethesda, MD 20892 USA.
[Wang, Gene-Jack; Fowler, Joanna S.; Wang, Ruiliang; Alexoff, Dave; Logan, Jean; Wong, Christopher; Pradhan, Kith; Caparelli, Elisabeth C.] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
RP Volkow, ND (reprint author), NIDA, 6001 Execut Blvd,Room 5274,MSC 9581, Bethesda, MD 20892 USA.
EM nvolkow@nida.nih.gov
RI Tomasi, Dardo/J-2127-2015;
OI Logan, Jean/0000-0002-6993-9994
FU NIH (NIAAA)
FX We thank David Schlyer, Don Warner, Paul Vaska, Colleen Shea, Youwen Xu,
Lisa Muench, Barbara Hubbard, Pauline Carter, Karen Apelskog, and Linda
Thomas for their contributions. Research supported by NIH's Intramural
Research Program (NIAAA).
NR 46
TC 16
Z9 16
U1 0
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD JUN
PY 2010
VL 51
IS 2
BP 623
EP 628
DI 10.1016/j.neuroimage.2010.02.015
PG 6
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 589IT
UT WOS:000277141200013
PM 20156571
ER
PT J
AU Okun, E
Mattson, MP
Arumugam, TV
AF Okun, Eitan
Mattson, Mark P.
Arumugam, Thiruma V.
TI Involvement of Fc Receptors in Disorders of the Central Nervous System
SO NEUROMOLECULAR MEDICINE
LA English
DT Review
DE Fc receptors; Innate immunity; CNS; Neurons; Ischemic stroke;
Alzheimer's disease
ID AMYLOID-BETA-PEPTIDE; ISCHEMIC BRAIN-INJURY; AFFINITY IGE RECEPTOR;
TUMOR-NECROSIS-FACTOR; MAST-CELL ACTIVATION; MULTIPLE-SCLEROSIS
PATIENTS; TOLL-LIKE RECEPTORS; NF-KAPPA-B; GAMMA-RECEPTOR;
ALZHEIMERS-DISEASE
AB Immunoglobulins are proteins with a highly variable antigen-binding domain and a constant region (Fc domain) that binds to a cell surface receptor (FcR). Activation of FcRs in immune cells (lymphocytes, macrophages, and mast cells) triggers effector responses including cytokine production, phagocytosis, and degranulation. In addition to their roles in normal responses to infection or tissue injury, and in immune-related diseases, FcRs are increasingly recognized for their involvement in neurological disorders. One or more FcRs are expressed in microglia, astrocytes, oligodendrocytes, and neurons. Aberrant activation of FcRs in such neural cells may contribute to the pathogenesis of major neurodegenerative conditions including Alzheimer's disease, Parkinson's disease, ischemic stroke, and multiple sclerosis. On the other hand, FcRs may play beneficial roles in counteracting pathological processes; for e.g., FcRs may facilitate removal of amyloid peptides from the brain and so protect against Alzheimer's disease. Knowledge of the functions of FcRs in the nervous system in health and disease is leading to novel preventative and therapeutic strategies for stroke, Alzheimer's disease, and other neurological disorders.
C1 [Arumugam, Thiruma V.] Univ Queensland, Sch Biomed Sci, Brisbane, Qld 4072, Australia.
[Okun, Eitan; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
RP Arumugam, TV (reprint author), Univ Queensland, Sch Biomed Sci, Brisbane, Qld 4072, Australia.
EM t.arumugam@uq.edu.au
RI Arumugam, Thiruma/B-4898-2011; Mattson, Mark/F-6038-2012; okun,
eitan/K-1314-2016
OI okun, eitan/0000-0001-8474-1487
FU Intramural NIH HHS [Z01 AG000312-08, Z01 AG000313-08, Z01 AG000317-08]
NR 162
TC 48
Z9 49
U1 0
U2 17
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1535-1084
J9 NEUROMOL MED
JI Neuromol. Med.
PD JUN
PY 2010
VL 12
IS 2
SI SI
BP 164
EP 178
DI 10.1007/s12017-009-8099-5
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA 602RV
UT WOS:000278157400004
PM 19844812
ER
PT J
AU Lovinger, DM
AF Lovinger, David M.
TI Neurotransmitter roles in synaptic modulation, plasticity and learning
in the dorsal striatum
SO NEUROPHARMACOLOGY
LA English
DT Review
DE Long-term plasticity; Dopamine; Glutamate; Endocannabinoid; Instrumental
learning; Skill learning
ID LONG-TERM DEPRESSION; MEDIUM SPINY NEURONS; METABOTROPIC GLUTAMATE
RECEPTORS; ENDOCANNABINOID-DEPENDENT PLASTICITY; FAST-SPIKING
INTERNEURONS; CENTRAL-NERVOUS-SYSTEM; BASAL GANGLIA; CORTICOSTRIATAL
SYNAPSES; CHOLINERGIC INTERNEURONS; NUCLEUS-ACCUMBENS
AB The dorsal striatum is a large forebrain region involved in action initiation, timing, control, learning and memory. Learning and remembering skilled movement sequences requires the dorsal striatum, and striatal subregions participate in both goal-directed (action-outcome) and habitual (stimulus response) learning. Modulation of synaptic transmission plays a large part in controlling input to as well as the output from striatal medium spiny projection neurons (MSNs). Synapses in this brain region are subject to short-term modulation, including allosteric alterations in ion channel function and prominent presynaptic inhibition. Two forms of long-term synaptic plasticity have also been observed in striatum, long-term potentiation (LTP) and long-term depression (LTD). LTP at glutamatergic synapses onto MSNs involves activation of NMDA-type glutamate receptors and D1 dopamine or A2A adenosine receptors. Expression of LTP appears to involve postsynaptic mechanisms. LTD at glutamatergic synapses involves retrograde endocannabinoid signaling stimulated by activation of metabotropic glutamate receptors (mGluRs) and D2 dopamine receptors. While postsynaptic mechanisms participate in LTD induction, maintained expression involves presynaptic mechanisms. A similar form of LTD has also been observed at GABAergic synapses onto MSNs. Studies have just begun to examine the roles of synaptic plasticity in striatal-based learning. Findings to date indicate that molecules implicated in induction of plasticity participate in these forms of learning. Neurotransmitter receptors involved in LTP induction are necessary for proper skill and goal-directed instrumental learning. Interestingly, receptors involved in LTP and LTD at glutamatergic synapses onto MSNs of the "indirect pathway" appear to have important roles in habit learning. More work is needed to reveal if and when synaptic plasticity occurs during learning and if so what molecules and cellular processes, both short- and long-term, contribute to this plasticity. Published by Elsevier Ltd.
C1 NIAAA, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA.
RP Lovinger, DM (reprint author), NIAAA, Lab Integrat Neurosci, NIH, Room TS 11 5625 Fishers Lane, Rockville, MD 20852 USA.
EM lovindav@mail.nih.gov
FU Intramural NIH HHS [Z01 AA000407-06]
NR 143
TC 180
Z9 183
U1 1
U2 40
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD JUN
PY 2010
VL 58
IS 7
BP 951
EP 961
DI 10.1016/j.neuropharm.2010.01.008
PG 11
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 593QU
UT WOS:000277475900001
PM 20096294
ER
PT J
AU Ait-Ali, D
Stroth, N
Sen, JM
Eiden, LE
AF Ait-Ali, Djida
Stroth, Nikolas
Sen, Jyoti M.
Eiden, Lee E.
TI PACAP-cytokine interactions govern adrenal neuropeptide biosynthesis
after systemic administration of LPS (vol 58, pg 208, 2010)
SO NEUROPHARMACOLOGY
LA English
DT Correction
C1 [Ait-Ali, Djida; Stroth, Nikolas; Eiden, Lee E.] NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA.
[Sen, Jyoti M.] NIA, Lymphocyte Dev Unit, Immunol Lab, NIH, Baltimore, MD 21224 USA.
RP Eiden, LE (reprint author), NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, Bldg 49,Room 5A-38, Bethesda, MD 20892 USA.
EM eidenl@mail.nih.gov
NR 1
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 0028-3908
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD JUN
PY 2010
VL 58
IS 7
BP 1187
EP 1187
DI 10.1016/j.neuropharm.2010.03.009
PG 1
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 593QU
UT WOS:000277475900028
ER
PT J
AU Salvadore, G
Cornwell, BR
Sambataro, F
Latov, D
Colon-Rosario, V
Carver, F
Holroyd, T
DiazGranados, N
Machado-Vieira, R
Grillon, C
Drevets, WC
Zarate, CA
AF Salvadore, Giacomo
Cornwell, Brian R.
Sambataro, Fabio
Latov, David
Colon-Rosario, Veronica
Carver, Frederick
Holroyd, Tom
DiazGranados, Nancy
Machado-Vieira, Rodrigo
Grillon, Christian
Drevets, Wayne C.
Zarate, Carlos A., Jr.
TI Anterior Cingulate Desynchronization and Functional Connectivity with
the Amygdala During a Working Memory Task Predict Rapid Antidepressant
Response to Ketamine
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE major depressive disorder (MDD); magnetoencephalography (MEG); N-back;
biomarker; beta desynchronization
ID MAJOR DEPRESSIVE DISORDER; D-ASPARTATE ANTAGONIST; N-BACK TASK; MOOD
DISORDERS; BRAIN; THERAPY; FMRI; MAGNETOENCEPHALOGRAPHY;
HYPERACTIVATION; MEDICATION
AB Pregenual anterior cingulate cortex (pgACC) hyperactivity differentiates treatment responders from non-responders to various pharmacological antidepressant interventions, including ketamine, an N-methyl-D-aspartate receptor antagonist. Evidence of pgACC hyperactivition during non-emotional working memory tasks in patients with major depressive disorder (MDD) highlights the importance of this region for processing both emotionally salient and cognitive stimuli. However, it is unclear whether pgACC activity might serve as a potential biomarker of antidepressant response during working memory tasks as well, in line with previous research with emotionally arousing tasks. This study tested the hypothesis that during the N-back task, a widely used working memory paradigm, low pretreatment pgACC activity, as well as coherence between the pgACC and the amygdala, would be correlated with the clinical improvement after ketamine. Magnetoencephalography (MEG) recordings were obtained from 15 drug-free patients with MDD during working memory performance 1 to 3 days before receiving a single ketamine infusion. Functional activation patterns were analyzed using advanced MEG source analysis. Source coherence analyses were conducted to quantify the degree of long-range functional connectivity between the pgACC and the amygdala. Patients who showed the least engagement of the pgACC in response to increased working memory load showed the greatest symptomatic improvement within 4 h of ketamine administration (r = 0.82, p = 0.0002, false discovery rate (FDR) <0.05). Pretreatment functional connectivity between the pgACC and the left amygdala was negatively correlated with antidepressant symptom change (r = -0.73, p = 0.0021, FDR <0.05). These data implicate the pgACC and its putative interaction with the amygdala in predicting antidepressant response to ketamine in a working memory task context. Neuropsychopharmacology (2010) 35, 1415-1422; doi: 10.1038/npp.2010.24; published online 10 March 2010
C1 [Salvadore, Giacomo; Cornwell, Brian R.; Latov, David; Colon-Rosario, Veronica; DiazGranados, Nancy; Machado-Vieira, Rodrigo; Grillon, Christian; Zarate, Carlos A., Jr.] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
[Sambataro, Fabio] NIMH, Gene Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA.
[Carver, Frederick; Holroyd, Tom] NIMH, Magnetoencephalog Core Facil, NIH, Bethesda, MD 20892 USA.
[Drevets, Wayne C.] NIMH, Sect Neuroimaging Mood & Anxiety Disorders, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
RP Salvadore, G (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
EM salvadoreg@mail.nih.gov
RI Sambataro, Fabio/E-3426-2010; MACHADO-VIEIRA, RODRIGO/D-8293-2012
OI Sambataro, Fabio/0000-0003-2102-416X; MACHADO-VIEIRA,
RODRIGO/0000-0002-4830-1190
FU National Institute of Mental Health, National Institutes of Health, and
a National Alliance for Research on Schizophrenia and Depression
FX This research was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health, and
a National Alliance for Research on Schizophrenia and Depression Award
(CZ). Ioline Henter provided invaluable editorial assistance.
NR 46
TC 92
Z9 94
U1 3
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD JUN
PY 2010
VL 35
IS 7
BP 1415
EP 1422
DI 10.1038/npp.2010.24
PG 8
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 595PN
UT WOS:000277624600002
PM 20393460
ER
PT J
AU Gray, TR
Eiden, RD
Leonard, KE
Connors, G
Shisler, S
Huestis, MA
AF Gray, Teresa R.
Eiden, Rina D.
Leonard, Kenneth E.
Connors, Gerard
Shisler, Shannon
Huestis, Marilyn A.
TI Nicotine and metabolites in meconium as evidence of maternal cigarette
smoking during pregnancy and predictors of neonatal growth deficits
SO NICOTINE & TOBACCO RESEARCH
LA English
DT Article
ID PRENATAL TOBACCO-SMOKE; SELF-REPORTED SMOKING; SALIVA COTININE;
LIQUID-CHROMATOGRAPHY; MASS-SPECTROMETRY; FETAL EXPOSURE;
QUANTIFICATION; WOMEN; TOXICOLOGY; OUTCOMES
AB Many women continue tobacco use during pregnancy despite known adverse consequences on neonatal growth and development. Testing meconium, the first neonatal feces, for tobacco biomarkers offers objective evidence of prenatal tobacco exposure. However, relationships between the amount, frequency, and timing of cigarette smoking during gestation and tobacco biomarker meconium concentrations and neonatal outcomes are unclear.
Eighty-seven pregnant women provided detailed self-reports of daily tobacco consumption throughout pregnancy. Nicotine, cotinine, and trans-3'-hydroxycotinine were quantified in neonatal meconium by liquid chromatography-tandem mass spectrometry.
Among nonsmokers, all meconium specimens were negative, whereas nearly all meconium specimens were positive if the mother self-reported tobacco use into the third trimester. Tobacco biomarker concentrations were significantly albeit weakly correlated with mean cigarettes per day in the third trimester. Reduced birth weight, gestational age, or head circumference were observed if meconium contained one or more tobacco biomarkers, but deficits did not correlate with biomarker concentrations.
While previously thought to reflect second and third trimester drug exposure, meconium appears to reliably identify only third trimester drug use. While a 10 ng/g nicotine, cotinine, or trans-3'-hydroxycotinine cutoff in meconium was previously proposed to differentiate tobacco-exposed from nonexposed or passively exposed neonates, improved maternal self-reporting techniques in this cohort suggest that a lower cutoff, equivalent to the analytic limits of quantification, is more appropriate.
C1 [Gray, Teresa R.; Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Eiden, Rina D.; Leonard, Kenneth E.; Connors, Gerard; Shisler, Shannon] SUNY Buffalo, Res Inst Addict, Buffalo, NY 14260 USA.
RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU National Institute on Drug Abuse at the National Institutes of Health
[R01 DA 013190]
FX This work was supported by the National Institute on Drug Abuse at the
National Institutes of Health (Intramural Research Program and grant
number R01 DA 013190).
NR 29
TC 24
Z9 24
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-2203
J9 NICOTINE TOB RES
JI Nicotine Tob. Res.
PD JUN
PY 2010
VL 12
IS 6
BP 658
EP 664
DI 10.1093/ntr/ntq068
PG 7
WC Substance Abuse; Public, Environmental & Occupational Health
SC Substance Abuse; Public, Environmental & Occupational Health
GA 606QY
UT WOS:000278443500015
PM 20427459
ER
PT J
AU Mason, RP
Stadler, K
Fernandes, DC
Tanaka, LY
Francisco, LRM
Jeannette, VV
AF Mason, Ronald P.
Stadler, Krisztian
Fernandes, Denise C.
Tanaka, Leonardo Y.
Francisco, Laurindo R. M.
Jeannette, Vasquez-Vivar
TI CONSTITUTIVE NITRIC OXIDE SYNTHASE ACTIVATION IS A SIGNIFICANT ROUTE FOR
NITROGLYCERIN-MEDIATED VASODILATION
SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY
LA English
DT Meeting Abstract
CT 6th Int Conf on Biol, Chemistry, and Therapeutic Applications of Nitric
Oxide/2nd Int Conf NO and Cancer/10th Annual Meeting of the
Nitric-Oxide-Soc-Japan
CY JUN 14-18, 2010
CL Kyoto, JAPAN
SP Nitr Oxide Soc Japan
C1 [Mason, Ronald P.; Stadler, Krisztian] NIEHS, NIH, Lab Toxicol & Pharmacolgy, Bethesda, MD USA.
[Fernandes, Denise C.; Tanaka, Leonardo Y.; Francisco, Laurindo R. M.] Univ Sao Paulo, Sch Med, Vasc Biol Lab, BR-05508 Sao Paulo, Brazil.
[Jeannette, Vasquez-Vivar] Med Coll Wisconsin, Dept Biophys, Milwaukee, WI 53226 USA.
RI Fernandes, Denise/K-2267-2012
OI Fernandes, Denise/0000-0002-5056-5734
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1089-8603
J9 NITRIC OXIDE-BIOL CH
JI Nitric Oxide-Biol. Chem.
PD JUN
PY 2010
VL 22
SU S
BP S25
EP S25
DI 10.1016/j.niox.2010.05.070
PG 1
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 606PZ
UT WOS:000278440700067
ER
PT J
AU Wink, DA
Sharon, G
Christopher, S
Lisa, R
Stefan, A
AF Wink, David A.
Sharon, Glynn
Christopher, Switzer
Lisa, Ridnour
Stefan, Ambs
TI Pathways associate Nitric Oxide Synthase and Cycloxygenase-2 that Lead
to Poor Prognosis in Breast Cancer
SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY
LA English
DT Meeting Abstract
CT 6th Int Conf on Biol, Chemistry, and Therapeutic Applications of Nitric
Oxide/2nd Int Conf NO and Cancer/10th Annual Meeting of the
Nitric-Oxide-Soc-Japan
CY JUN 14-18, 2010
CL Kyoto, JAPAN
SP Nitr Oxide Soc Japan
C1 [Wink, David A.; Sharon, Glynn; Stefan, Ambs] Natl Canc Inst, Radiat Biol Branch, 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 1089-8603
J9 NITRIC OXIDE-BIOL CH
JI Nitric Oxide-Biol. Chem.
PD JUN
PY 2010
VL 22
SU S
BP S17
EP S18
DI 10.1016/j.niox.2010.05.046
PG 2
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 606PZ
UT WOS:000278440700043
ER
PT J
AU Bratus, AS
Posvyanskii, VP
Novozhilov, AS
AF Bratus, Alexander S.
Posvyanskii, Vladimir P.
Novozhilov, Artem S.
TI Existence and stability of stationary solutions to spatially extended
autocatalytic and hypercyclic systems under global regulation and with
nonlinear growth rates
SO NONLINEAR ANALYSIS-REAL WORLD APPLICATIONS
LA English
DT Article
DE Autocatalytic system; Hypercycle; Reaction-diffusion; Non-uniform
stationary solutions; Stability
ID EVOLUTION; MODEL; DIFFUSION; PARASITES; ORIGIN; LIFE
AB An analytical analysis of spatially extended autocatalytic and hypercyclic systems is presented. It is shown that spatially explicit systems in the form of reaction-diffusion equations with global regulation possess the same major qualitative features as the corresponding local models. In particular, using the introduced notion of the stability in the mean integral sense we prove the competitive exclusion principle for the autocatalytic system and the permanence for the hypercycle system. Existence and stability of stationary solutions are studied. For some parameter values it is proved that stable spatially non-uniform solutions appear. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Novozhilov, Artem S.] NIH, Bethesda, MD 20894 USA.
[Bratus, Alexander S.; Posvyanskii, Vladimir P.] Moscow State Univ Railway Engn, Moscow, Russia.
RP Novozhilov, AS (reprint author), NIH, 8600 Rockville Pike, Bethesda, MD 20894 USA.
RI Novozhilov, Artem/D-7544-2012; Novozhilov, Artem/C-9248-2013
OI Novozhilov, Artem/0000-0001-5469-2557
FU Department of Health (NIH, National Library of Medicine)
FX The authors are grateful to Dr. Yu. Semenov for the help with the proof
of Lemma 4.2. The research of ASN is supported by the Department of
Health and Human Services intramural program (NIH, National Library of
Medicine).
NR 32
TC 4
Z9 5
U1 0
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1468-1218
J9 NONLINEAR ANAL-REAL
JI Nonlinear Anal.-Real World Appl.
PD JUN
PY 2010
VL 11
IS 3
BP 1897
EP 1917
DI 10.1016/j.nonrwa.2009.04.013
PG 21
WC Mathematics, Applied
SC Mathematics
GA 610WE
UT WOS:000278768800064
PM 20596239
ER
PT J
AU Takata, K
Arana, ME
Seki, M
Kunkel, TA
Wood, RD
AF Takata, Kei-ichi
Arana, Mercedes E.
Seki, Mineaki
Kunkel, Thomas A.
Wood, Richard D.
TI Evolutionary conservation of residues in vertebrate DNA polymerase N
conferring low fidelity and bypass activity
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID THYMINE GLYCOL; BINDING; THETA; POLQ; PROCESSIVITY; SPECIFICITY;
EFFICIENCY; SUBDOMAIN; FRAGMENT; MUTANTS
AB POLN is a nuclear A-family DNA polymerase encoded in vertebrate genomes. POLN has unusual fidelity and DNA lesion bypass properties, including strong strand displacement activity, low fidelity favoring incorporation of T for template G and accurate translesion synthesis past a 5S-thymine glycol (5S-Tg). We searched for conserved features of the polymerase domain that distinguish it from prokaryotic pol I-type DNA polymerases. A Lys residue (679 in human POLN) of particular interest was identified in the conserved 'O-helix' of motif 4 in the fingers sub-domain. The corresponding residue is one of the most important for controlling fidelity of prokaryotic pol I and is a nonpolar Ala or Thr in those enzymes. Kinetic measurements show that K679A or K679T POLN mutant DNA polymerases have full activity on nondamaged templates, but poorly incorporate T opposite template G and do not bypass 5S-Tg efficiently. We also found that a conserved Tyr residue in the same motif not only affects sensitivity to dideoxynucleotides, but also greatly influences enzyme activity, fidelity and bypass. Protein sequence alignment reveals that POLN has three specific insertions in the DNA polymerase domain. The results demonstrate that residues have been strictly retained during evolution that confer unique bypass and fidelity properties on POLN.
C1 [Takata, Kei-ichi; Wood, Richard D.] Univ Texas MD Anderson Canc Ctr, Univ Texas Houston, Dept Carcinogenesis, Grad Sch Biomed Sci,Res Div, Res Triangle Pk, NC USA.
[Arana, Mercedes E.; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Arana, Mercedes E.; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Seki, Mineaki] Osaka Univ, Grad Sch Frontier Biosci, Suita, Osaka 565, Japan.
RP Wood, RD (reprint author), Univ Texas MD Anderson Canc Ctr, Univ Texas Houston, Dept Carcinogenesis, Grad Sch Biomed Sci,Res Div, Sci Pk, Res Triangle Pk, NC USA.
EM rwood@mdanderson.org
RI Wood, Richard/E-7855-2011
OI Wood, Richard/0000-0002-9495-6892
FU National Institutes of Health [CA101980]; University of Pittsburgh
Cancer Institute; Division of Intramural Research of the National
Institutes of Health [Z01 ES065070]; National Institute of Environmental
Health Sciences
FX FUNDING; National Institutes of Health (CA101980 to R.D.W.); the
University of Pittsburgh Cancer Institute; and the Grady F. Saunders,
Ph.D. Endowed Professorship; Division of Intramural Research of the
National Institutes of Health Project (Z01 ES065070 to T.A.K. and M.A.)
in part; National Institute of Environmental Health Sciences. Funding
for open access charge: MD Anderson Endowed Professorship.
NR 28
TC 17
Z9 17
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JUN
PY 2010
VL 38
IS 10
BP 3233
EP 3244
DI 10.1093/nar/gkq048
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 606QQ
UT WOS:000278442600015
PM 20144948
ER
PT J
AU Zhou, H
Mazan-Mamczarz, K
Martindale, JL
Barker, A
Liu, ZQ
Gorospe, M
Leedman, PJ
Gartenhaus, RB
Hamburger, AW
Zhang, YX
AF Zhou, Hua
Mazan-Mamczarz, Krystyna
Martindale, Jennifer L.
Barker, Andrew
Liu, Zhenqiu
Gorospe, Myriam
Leedman, Peter J.
Gartenhaus, Ronald B.
Hamburger, Anne W.
Zhang, Yuexing
TI Post-transcriptional regulation of androgen receptor mRNA by an ErbB3
binding protein 1 in prostate cancer
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID 67-KDA POLYPEPTIDE P67; GENE-EXPRESSION; MEDIATED TRANSCRIPTION;
INITIATION-FACTOR; CELL-GROWTH; EBP1; PHOSPHORYLATION; PROGRESSION;
INHIBITION; REPRESSION
AB Androgen receptor (AR)-mediated pathways play a critical role in the development and progression of prostate cancer. However, little is known about the regulation of AR mRNA stability and translation, two central processes that control AR expression. The ErbB3 binding protein 1 (EBP1), an AR corepressor, negatively regulates crosstalk between ErbB3 ligand heregulin (HRG)-triggered signaling and the AR axis, affecting biological properties of prostate cancer cells. EBP1 protein expression is also decreased in clinical prostate cancer. We previously demonstrated that EBP1 overexpression results in decreased AR protein levels by affecting AR promoter activity. However, EBP1 has recently been demonstrated to be an RNA binding protein. We therefore examined the ability of EBP1 to regulate AR post-transcriptionally. Here we show that EBP1 promoted AR mRNA decay through physical interaction with a conserved UC-rich motif within the 3'-UTR of AR. The ability of EBP1 to accelerate AR mRNA decay was further enhanced by HRG treatment. EBP1 also bound to a CAG-formed stem-loop in the 5' coding region of AR mRNA and was able to inhibit AR translation. Thus, decreases of EBP1 in prostate cancer could be important for the post-transcriptional up-regulation of AR contributing to aberrant AR expression and disease progression.
C1 [Zhou, Hua; Mazan-Mamczarz, Krystyna; Liu, Zhenqiu; Gartenhaus, Ronald B.; Hamburger, Anne W.; Zhang, Yuexing] Univ Maryland, Sch Med, Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
[Zhou, Hua; Hamburger, Anne W.; Zhang, Yuexing] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA.
[Martindale, Jennifer L.; Gorospe, Myriam] NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Baltimore, MD 21228 USA.
[Barker, Andrew; Leedman, Peter J.] Univ Western Australia, Univ Dept Med, Perth, WA 6000, Australia.
[Barker, Andrew; Leedman, Peter J.] Univ Western Australia, Western Australian Inst Med Res, Lab Canc Med, Perth, WA 6000, Australia.
RP Zhang, YX (reprint author), Univ Maryland, Sch Med, Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
EM yzhan001@umaryland.edu
RI Barker, Andrew/A-4289-2013; Leedman, Peter/O-4044-2014
FU Maryland Technology Corporation; Department of Defense [W81XWH-07-0267];
National Institutes of Health [R01 CA76047, R21 088882-01]; Department
of Pathology; National Institutes of Health
FX Maryland Technology Corporation (June 6, 2006) and Department of Defense
grant W81XWH-07-0267 (Y.Z.) and National Institutes of Health grants R01
CA76047 and R21 088882-01 and a grant from the Department of Pathology
(A.W.H.). M.G. and J.L.M. are supported by the National Institute on
Aging-Intramural Research Program, National Institutes of Health.
Funding for open access charge: W81XWH-07-0267 (Y.Z.).
NR 50
TC 19
Z9 20
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JUN
PY 2010
VL 38
IS 11
BP 3619
EP 3631
DI 10.1093/nar/gkq084
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 616DM
UT WOS:000279188800020
PM 20159994
ER
PT J
AU Fozo, EM
Makarova, KS
Shabalina, SA
Yutin, N
Koonin, EV
Storz, G
AF Fozo, Elizabeth M.
Makarova, Kira S.
Shabalina, Svetlana A.
Yutin, Natalya
Koonin, Eugene V.
Storz, Gisela
TI Abundance of type I toxin-antitoxin systems in bacteria: searches for
new candidates and discovery of novel families
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID RNA SECONDARY STRUCTURE; SOS-INDUCED TOXIN; ESCHERICHIA-COLI;
BACILLUS-SUBTILIS; ANTISENSE RNA; PROTEIN; SEQUENCES; PAR; EXPRESSION;
PREDICTION
AB Small, hydrophobic proteins whose synthesis is repressed by small RNAs (sRNAs), denoted type I toxin-antitoxin modules, were first discovered on plasmids where they regulate plasmid stability, but were subsequently found on a few bacterial chromosomes. We used exhaustive PSI-BLAST and TBLASTN searches across 774 bacterial genomes to identify homologs of known type I toxins. These searches substantially expanded the collection of predicted type I toxins, revealed homology of the Ldr and Fst toxins, and suggested that type I toxin-antitoxin loci are not spread by horizontal gene transfer. To discover novel type I toxin-antitoxin systems, we developed a set of search parameters based on characteristics of known loci including the presence of tandem repeats and clusters of charged and bulky amino acids at the C-termini of short proteins containing predicted transmembrane regions. We detected sRNAs for three predicted toxins from enterohemorrhagic Escherichia coli and Bacillus subtilis, and showed that two of the respective proteins indeed are toxic when overexpressed. We also demonstrated that the local free-energy minima of RNA folding can be used to detect the positions of the sRNA genes. Our results suggest that type I toxin-antitoxin modules are much more widely distributed among bacteria than previously appreciated.
C1 [Fozo, Elizabeth M.; Storz, Gisela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20894 USA.
[Makarova, Kira S.; Shabalina, Svetlana A.; Yutin, Natalya; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
RP Storz, G (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20894 USA.
EM storz@helix.nih.gov
RI Shabalina, Svetlana/N-8939-2013;
OI Shabalina, Svetlana/0000-0003-2272-7473; Storz,
Gisela/0000-0001-6698-1241
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; National Center for Biotechnology Information; National
Research Council
FX Intramural Research Programs of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (E.M.F. and G.S.) and
National Center for Biotechnology Information (K.S.M., S.A.S., N.Y. and
E.V.K.) and a Research Associateship from the National Research Council
(E.M.F.). Funding for open access charge: Intramural program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development.
NR 38
TC 112
Z9 116
U1 1
U2 12
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JUN
PY 2010
VL 38
IS 11
BP 3743
EP 3759
DI 10.1093/nar/gkq054
PG 17
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 616DM
UT WOS:000279188800030
PM 20156992
ER
PT J
AU Abbas, AI
Urban, DJ
Jensen, NH
Farrell, MS
Kroeze, WK
Mieczkowski, P
Wang, ZF
Roth, BL
AF Abbas, Atheir I.
Urban, Daniel J.
Jensen, Niels H.
Farrell, Martilias S.
Kroeze, Wesley K.
Mieczkowski, Piotr
Wang, Zefeng
Roth, Bryan L.
TI Assessing serotonin receptor mRNA editing frequency by a novel ultra
high-throughput sequencing method
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID 2C RECEPTOR; 5-HT2C RECEPTOR; REVERSIBLE TERMINATOR; HUMAN
TRANSCRIPTOME; PREFRONTAL CORTEX; NERVOUS-SYSTEM; RAT-BRAIN; ADULT-RAT;
GENE; BEHAVIOR
AB RNA editing is a post-transcriptional modification of pre-mRNA that results in increased diversity in transcriptomes and proteomes. It occurs in a wide variety of eukaryotic organisms and in some viruses. One of the most common forms of pre-mRNA editing is A-to-I editing, in which adenosine is deaminated to inosine, which is read as guanosine during translation. This phenomenon has been observed in numerous transcripts, including the mammalian 5-HT(2C) receptor, which can be edited at five distinct sites. Methods used to date to quantify 5-HT(2C) receptor editing are labor-intensive, expensive and provide limited information regarding the relative abundance of 5-HT(2C) receptor editing variants. Here, we present a novel, ultra high-throughput method to quantify 5-HT(2C) receptor editing, compare it to a more conventional method, and use it to assess the effect of a range of genetic and pharmacologic manipulations on 5-HT(2C) editing. We conclude that this new method is powerful and economical, and we provide evidence that alterations in 5-HT(2C) editing appear to be a result of regional changes in brain activity, rather than a mechanism to normalize 5-HT(2C) signaling.
C1 [Roth, Bryan L.] Univ N Carolina, Dept Pharmacol, Natl Inst Mental Hlth, Psychoact Drug Screening Program,Sch Med, Chapel Hill, NC 27599 USA.
[Mieczkowski, Piotr] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
[Roth, Bryan L.] Univ N Carolina, Dept Psychiat, Sch Med, Chapel Hill, NC 27599 USA.
[Roth, Bryan L.] Univ N Carolina, Lineberger Canc Ctr, Sch Med, Chapel Hill, NC 27599 USA.
[Roth, Bryan L.] Univ N Carolina, Dept Med Chem, Sch Pharm, Chapel Hill, NC 27599 USA.
[Abbas, Atheir I.] Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA.
RP Roth, BL (reprint author), Univ N Carolina, Dept Pharmacol, Natl Inst Mental Hlth, Psychoact Drug Screening Program,Sch Med, Chapel Hill, NC 27599 USA.
EM bryan_roth@med.unc.edu
RI Roth, Bryan/F-3928-2010;
OI Wang, Zefeng/0000-0002-6605-3637
FU NIMH [NIMH61887, U19MH82441]; CWRU MSTP; National Institutes of Health
[U19MH82441, T32 GM007250, RO1MH61887]; UNC Chapel Hill; Lineberger
Cancer Center
FX FUNDING; NIMH61887, U19MH82441; NIMH Psychoactive Drug Screening Program
(to A.A., D.U., M.S.F., N.H.J., W.K.K., B.L.R.); NARSAD Distinguished
Investigator (to B.L.R.); CWRU MSTP and National Institutes of Health
(T32 GM007250 to A.A.); UNC Chapel Hill and the Lineberger Cancer
Center. Funding for open access charge: National Institutes of Health
(U19MH82441, RO1MH61887).
NR 55
TC 22
Z9 23
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JUN
PY 2010
VL 38
IS 10
AR e118
DI 10.1093/nar/gkq107
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 606QQ
UT WOS:000278442600007
PM 20185571
ER
PT J
AU Ishihara, S
Varma, R
Schwartz, RH
AF Ishihara, Satoru
Varma, Rajat
Schwartz, Ronald H.
TI A new fractionation assay, based on the size of
formaldehyde-crosslinked, mildly sheared chromatin, delineates the
chromatin structure at promoter regions
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID BETA-GLOBIN GENE; NUCLEOSOME CORE PARTICLE; IN-VIVO; ANGSTROM
RESOLUTION; T-CELLS; IMMUNOPRECIPITATION; PROTEIN; GENOME
AB To explore the higher order structure of transcribable chromatin in vivo, its local configuration was assessed through the accessibility of the chromatin to crosslinking with formaldehyde. The application of crosslinked and mildly sheared chromatin to sedimentation velocity centrifugation followed by size-fractionation of the DNA enabled us to biochemically distinguish between chromatin with heavily versus sparsely crosslinkable structures. The separated fractions showed a good correlation with gene expression profiles. Genes with poor crosslinking around the promoter region were actively transcribed, while transcripts were hardly detected from genes with extensive crosslinking in their promoter regions. For the inducible gene, Il2, the distribution of the promoter shifted in the gradient following T-cell receptor stimulation, consistent with a change in structure at this locus during activation. The kinetics of this switch preceded the chromatin change observed in a DNase I accessibility assay. Thus, this new chromatin fractionation technique has revealed a change in chromatin structure that has not been previously characterized.
C1 [Ishihara, Satoru; Varma, Rajat; Schwartz, Ronald H.] NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Ishihara, Satoru] Fujita Hlth Univ, Sch Med, Dept Biochem, Aichi 4701192, Japan.
RP Ishihara, S (reprint author), NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA.
EM satorui@fujita-hu.ac.jp
RI Varma, Rajat/I-1209-2012
OI Varma, Rajat/0000-0001-5131-0402
FU Division of Intramural Research; National Institute of Allergy and
Infectious Diseases; National Institutes of Health; Laboratory of
Cellular and Molecular Immunology, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX Division of Intramural Research; National Institute of Allergy and
Infectious Diseases; National Institutes of Health. Funding for open
access charge: Laboratory of Cellular and Molecular Immunology, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health.
NR 25
TC 6
Z9 6
U1 0
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JUN
PY 2010
VL 38
IS 11
AR e124
DI 10.1093/nar/gkq203
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 616DM
UT WOS:000279188800006
PM 20371521
ER
PT J
AU Debisette, AT
Martinelli, AM
Couig, MP
Braun, M
AF Debisette, Annette Tyree
Martinelli, Angela M.
Couig, Mary Pat
Braun, Michelle
TI US Public Health Service Commissioned Corps Nurses: Responding in Times
of National Need
SO NURSING CLINICS OF NORTH AMERICA
LA English
DT Article
DE US Public Health Service; Emergency preparedness; Disaster response;
Public health service nursing; Commissioned Corps
AB The US Public Health Service (PHS) is one of 7 uniformed services operating for the nation. Nurses form the largest category of personnel in the PHS and are integral members of teams identified to deploy in times of national need. PHS nurses serve "in harm's way" to protect and defend the public health of the nation during national emergencies and disasters of great magnitude, such as 9/11, Hurricane Katrina, the H1N1 virus outbreak, and so forth. In this article, the authors discuss how active-duty Commissioned Corps nurses in the US PHS respond during times of national need. Military nurses may be asked to serve in war zones, participate in humanitarian missions, and care for military beneficiaries. By contrast, the role of nurses in the Commissioned Corps is to protect, defend, and advance the public health of the nation. PHS nurses are critical members of interdisciplinary health care teams organized to provide health care to diverse populations in the United States and abroad.
C1 [Debisette, Annette Tyree] US PHS, US FDA, Off Regulatory Affairs, Div Human Resource Dev, Rockville, MD 20852 USA.
[Martinelli, Angela M.] NIAAA, Div Treatment & Recovery Res, Rockville, MD 20852 USA.
[Couig, Mary Pat] US PHS, Bethesda, MD 20815 USA.
[Braun, Michelle] NIH, US Publ Hlth Serv, Kidney Dis Sect, Ctr Clin, Bethesda, MD 20892 USA.
RP Debisette, AT (reprint author), US PHS, US FDA, Off Regulatory Affairs, Div Human Resource Dev, 11919 Rockville Pike, Rockville, MD 20852 USA.
EM Annette.debisette@fda.hhs.gov
NR 7
TC 3
Z9 3
U1 1
U2 4
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0029-6465
J9 NURS CLIN N AM
JI Nurs. Clin. North Am.
PD JUN
PY 2010
VL 45
IS 2
BP 123
EP +
DI 10.1016/j.cnur.2010.02.003
PG 15
WC Nursing
SC Nursing
GA 618FT
UT WOS:000279337600004
PM 20510699
ER
PT J
AU Knebel, AR
Martinelli, AM
Orsega, S
Doss, TL
Balingit-Wines, AM
Konchan, CL
AF Knebel, Ann R.
Martinelli, Angela M.
Orsega, Susan
Doss, Thomas L.
Balingit-Wines, Ana Marie
Konchan, Carol L.
TI Ground Zero Recollections of US Public Health Service Nurses Deployed to
New York City in September 2001
SO NURSING CLINICS OF NORTH AMERICA
LA English
DT Article
DE US Public Health Service; Emergency preparedness; September 11; World
Trade Center; Disaster response; Public health service nursing
ID TRADE-CENTER DISASTER; RECOVERY; WORKERS; RESCUE
AB The events of September 11, 2001, set in motion the broadest emergency response ever conducted by the US Department of Health and Human Services. In this article, some of the nurses who deployed to New York City in the aftermath of that horrific attack on the United States offer their recollections of the events. Although Public Health Service Commissioned Corps (PHS CC) officers participated in deployments before 9/11, this particular deployment accelerated the transformation of the PHS CC, because people came to realize the tremendous potential of a uniformed service of 6,000 health care professionals. When not responding to emergencies, PHS CC nurses daily serve the mission of the PHS to protect, promote, and advance the health and safety of the nation. In times of crisis, the PHS CC nurses stand ready to deploy in support of those in need of medical assistance.
C1 [Knebel, Ann R.] US Dept Hlth & Human Serv, Off Assistant Secretary Preparedness & Response, Washington, DC 20201 USA.
[Knebel, Ann R.; Martinelli, Angela M.; Orsega, Susan; Doss, Thomas L.; Balingit-Wines, Ana Marie; Konchan, Carol L.] US Publ Hlth Serv Commissioned Corps PHS CC, Off Publ Hlth & Sci, US Dept Hlth & Human Serv, Washington, DC 20201 USA.
[Martinelli, Angela M.] NIAAA, Div Treatment & Recovery, Rockville, MD 20852 USA.
[Orsega, Susan] NIAID, Div Clin Res, Collaborat Clin Res Branch, Bethesda, MD 20892 USA.
[Doss, Thomas L.] Dept Def TRICARE Management Act, Falls Church, VA 22041 USA.
[Balingit-Wines, Ana Marie] US Dept Hlth & Human Serv, FDA Ctr Devices & Radiol Hlth, US FDA, Off Compliance, Silver Spring, MD 20993 USA.
[Konchan, Carol L.] NINDS, US Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
RP Knebel, AR (reprint author), US Dept Hlth & Human Serv, Off Assistant Secretary Preparedness & Response, 200 Independence Ave SW,Room 638 G, Washington, DC 20201 USA.
EM ann.knebel@hhs.gov
NR 21
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U1 3
U2 4
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0029-6465
J9 NURS CLIN N AM
JI Nurs. Clin. North Am.
PD JUN
PY 2010
VL 45
IS 2
BP 137
EP +
DI 10.1016/j.cnur.2010.02.010
PG 17
WC Nursing
SC Nursing
GA 618FT
UT WOS:000279337600005
PM 20510700
ER
PT J
AU Calzone, K
Jenkins, J
AF Calzone, Kathleen
Jenkins, Jean
TI Development of a genetics/genomic resource tool kit to facilitate
health-care professional education
SO NURSING & HEALTH SCIENCES
LA English
DT Meeting Abstract
C1 [Calzone, Kathleen] NCI, Bethesda, MD 20892 USA.
[Jenkins, Jean] NHGRI, Bethesda, MD 20892 USA.
EM calzonek@mail.nih.gov
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 1441-0745
J9 NURS HEALTH SCI
JI Nurs. Health Sci.
PD JUN
PY 2010
VL 12
IS 2
BP 276
EP 277
PG 2
WC Nursing
SC Nursing
GA 599NQ
UT WOS:000277920500026
ER
PT J
AU Calzone, K
Jenkins, J
Somerset, PH
AF Calzone, Kathleen
Jenkins, Jean
Somerset, Paul Hoernes
TI Establishing online unfolding case study simulations for genetic/genomic
nursing education
SO NURSING & HEALTH SCIENCES
LA English
DT Meeting Abstract
C1 [Calzone, Kathleen] NCI, Bethesda, MD 20892 USA.
[Jenkins, Jean] NHGRI, Bethesda, MD 20892 USA.
[Somerset, Paul Hoernes] Whelkum Prod, Lewes, DE USA.
EM calzonek@mail.nih.gov
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 1441-0745
J9 NURS HEALTH SCI
JI Nurs. Health Sci.
PD JUN
PY 2010
VL 12
IS 2
BP 276
EP 276
PG 1
WC Nursing
SC Nursing
GA 599NQ
UT WOS:000277920500025
ER
PT J
AU Howard, BV
Comuzzie, A
Devereux, RB
Ebbesson, SOE
Fabsitz, RR
Howard, WJ
Laston, S
MacCluer, JW
Silverman, A
Umans, JG
Wang, H
Weissman, NJ
Wenger, CR
AF Howard, Barbara V.
Comuzzie, Anthony
Devereux, Richard B.
Ebbesson, Sven O. E.
Fabsitz, Richard R.
Howard, Wm. James
Laston, Sandra
MacCluer, Jean W.
Silverman, Angela
Umans, Jason G.
Wang, Hong
Weissman, Neil J.
Wenger, Charlotte R.
TI Cardiovascular disease prevalence and its relation to risk factors in
Alaska Eskimos
SO NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES
LA English
DT Article
DE Cardiovascular disease; Risk factors; Epidemiology; Omega-3 fatty acid
ID CORONARY-HEART-DISEASE; PHYSICAL-ACTIVITY; AMERICAN-INDIANS;
ARTERY-DISEASE; CAROTID ATHEROSCLEROSIS; DIABETES-MELLITUS; NATIVES
GOCADAN; INUIT; POPULATION; PREVENTION
AB Background and aims: Although Eskimos were thought to be protected from cardiovascular disease (CVD), state health data show a large proportion of deaths from CVD, despite traditional lifestyles and high omega-3 fatty acid intake. This article explores CVD prevalence and its relation to risk factors in Alaska Eskimos.
Methods and results: A population-based cohort of 499 Alaska Eskimos > age 45 from the Norton Sound region was examined in 2000-2004 for CVD and associated risk factors as part of the Genetics of Coronary Artery Disease in Alaska Natives study. CVD and atherosclerosis were evaluated and adjudicated using standardized methods. Average age was 58 years; diabetes prevalence was low and high-density lipoprotein cholesterol (HDL-C) concentrations were high, but a large proportion smoked and had high pathogen burden. CVD was higher in men (12.6%) than in women (5.3%) (prevalence ratio 2.4, CI 1.3-4.4). Rates of stroke (6.1% in men, 1.8% in women) were similar to those for coronary heart disease (CHD) (6.1% men, 2.5% women). MI prevalence was low in both genders (1.9% and 0.7%). CVD was higher in men and in those >60 years. Hypertension, diabetes, high LDL-C, high apoB, and low HDL-C were all strong correlates (<.002) and albuminuria and CRP were also correlated with CVD (p < .05) after adjustment for age and gender. Carotid atherosclerosis was correlated with CVD (p = .0079) independent of other risk factors.
Conclusion: These data show high CHD and stroke prevalence in Alaska Eskimos, despite low average LDL-C and high HDL-C. Hypertension and high LDL-C were independent correlates; identifying these risk factors early and treating to target is recommended. (C) 2009 Published by Elsevier B.V.
C1 [Howard, Barbara V.; Silverman, Angela; Umans, Jason G.; Wang, Hong; Weissman, Neil J.] Georgetown Univ, MedStar Res Inst, Hyattsville, MD 20783 USA.
[Comuzzie, Anthony; Laston, Sandra; MacCluer, Jean W.; Wenger, Charlotte R.] SW Fdn Biomed Res, San Antonio, TX 78284 USA.
[Devereux, Richard B.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA.
[Ebbesson, Sven O. E.] Norton Sound Hlth Corp, Nome, AK USA.
[Fabsitz, Richard R.] NHLBI, Bethesda, MD 20892 USA.
[Howard, Wm. James] Washington Hosp Ctr, Washington, DC 20010 USA.
RP Howard, BV (reprint author), Georgetown Univ, MedStar Res Inst, 6495 New Hampshire Ave,Suite 201, Hyattsville, MD 20783 USA.
EM barbara.v.howard@medstar.net
FU National Heart, Lung, and Blood Institute, Bethesda, MD [RO1-HL64244,
U01 HL082458, M10RR0047-34]
FX This study was funded by grants RO1-HL64244, U01 HL082458, and
M10RR0047-34 (GCRC) from the National Heart, Lung, and Blood Institute,
Bethesda, MD.
NR 39
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U1 0
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0939-4753
J9 NUTR METAB CARDIOVAS
JI Nutr. Metab. Carbiovasc. Dis.
PD JUN
PY 2010
VL 20
IS 5
BP 350
EP 358
DI 10.1016/j.numecd.2009.04.010
PG 9
WC Cardiac & Cardiovascular Systems; Endocrinology & Metabolism; Nutrition
& Dietetics
SC Cardiovascular System & Cardiology; Endocrinology & Metabolism;
Nutrition & Dietetics
GA 630VY
UT WOS:000280304300008
PM 19800772
ER
PT J
AU Greenlee, RT
Kessel, B
Williams, CR
Riley, TL
Ragard, LR
Hartge, P
Buys, SS
Partridge, EE
Reding, DJ
AF Greenlee, Robert T.
Kessel, Bruce
Williams, Craig R.
Riley, Thomas L.
Ragard, Lawrence R.
Hartge, Patricia
Buys, Saundra S.
Partridge, Edward E.
Reding, Douglas J.
TI Prevalence, Incidence, and Natural History of Simple Ovarian Cysts Among
Women > 55 Years Old in a Large Cancer Screening Trial
SO OBSTETRICAL & GYNECOLOGICAL SURVEY
LA English
DT Editorial Material
C1 [Greenlee, Robert T.] Marshfield Clin Res Fdn, Epidemiol Res Ctr, Marshfield, WI USA.
Pacific Hlth Res Inst, Honolulu, HI USA.
Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA.
Informat Management Serv Inc, Rockville, MD USA.
WESTAT Corp, Rockville, MD 20850 USA.
NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA.
Univ Alabama, Birmingham, AL USA.
Marshfield Clin Fdn Med Res & Educ, Marshfield, WI USA.
RP Greenlee, RT (reprint author), Marshfield Clin Res Fdn, Epidemiol Res Ctr, Marshfield, WI USA.
OI Kessel, Bruce/0000-0001-9979-2068
NR 0
TC 13
Z9 13
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7828
J9 OBSTET GYNECOL SURV
JI Obstet. Gynecol. Surv.
PD JUN
PY 2010
VL 65
IS 6
BP 373
EP 374
DI 10.1097/OGX.0b013e3181e5a0d0
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 628FQ
UT WOS:000280100500013
ER
PT J
AU Rodriguez, AC
Schiffman, M
Herrero, R
Hildesheim, A
Bratti, C
Sherman, ME
Solomon, D
Guillen, D
Alfaro, M
Morales, J
Hutchinson, M
Katki, H
Cheung, L
Wacholder, S
Burk, RD
AF Cecilia Rodriguez, Ana
Schiffman, Mark
Herrero, Rolando
Hildesheim, Allan
Bratti, Concepcion
Sherman, Mark E.
Solomon, Diane
Guillen, Diego
Alfaro, Mario
Morales, Jorge
Hutchinson, Martha
Katki, Hormuzd
Cheung, Li
Wacholder, Sholom
Burk, Robert D.
TI Longitudinal Study of Human Papillomavirus Persistence and Cervical
Intraepithelial Neoplasia Grade 2/3: Critical Role of Duration of
Infection
SO OBSTETRICAL & GYNECOLOGICAL SURVEY
LA English
DT Editorial Material
C1 [Cecilia Rodriguez, Ana] INCIENSA Fdn, San Jose, Costa Rica.
NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD USA.
NCI, Canc Prevent Div, NIH, DHHS, Rockville, MD USA.
Brown Univ, Women & Infants Hosp, Dept Pathol, Providence, RI USA.
Informat Management Serv Inc, Silver Spring, MD USA.
Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA.
Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA.
Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
Albert Einstein Coll Med, Dept Obstet Gynecol & Womens Hlth, Bronx, NY 10467 USA.
RP Rodriguez, AC (reprint author), INCIENSA Fdn, San Jose, Costa Rica.
RI Hildesheim, Allan/B-9760-2015
OI Hildesheim, Allan/0000-0003-0257-2363
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7828
J9 OBSTET GYNECOL SURV
JI Obstet. Gynecol. Surv.
PD JUN
PY 2010
VL 65
IS 6
BP 374
EP 376
DI 10.1097/OGX.0b013e3181e5a0ed
PG 3
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 628FQ
UT WOS:000280100500014
ER
PT J
AU Wylie, BJ
Gilbert, S
Landon, MB
Spong, CY
Rouse, DJ
Leveno, KJ
Varner, MW
Caritis, SN
Meis, PJ
Wapner, RJ
Sorokin, Y
Miodovnik, M
O'Sullivan, MJ
Sibai, BM
Langer, O
AF Wylie, Blair J.
Gilbert, Sharon
Landon, Mark B.
Spong, Catherine Y.
Rouse, Dwight J.
Leveno, Kenneth J.
Varner, Michael W.
Caritis, Steve N.
Meis, Paul J.
Wapner, Ronald J.
Sorokin, Yoram
Miodovnik, Menachem
O'Sullivan, Mary J.
Sibai, Baha M.
Langer, Oded
CA Eunice Kennedy Shriver NICHD
TI Comparison of Transverse and Vertical Skin Incision for Emergency
Cesarean Delivery
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID OUTCOMES
AB OBJECTIVE: To compare incision-to-delivery intervals and related maternal and neonatal outcomes by skin incision in primary and repeat emergent cesarean deliveries.
METHODS: From 1999 to 2000, a prospective cohort study of all cesarean deliveries was conducted at 13 hospitals comprising the Eunice Kennedy Shriver National Institute of Child Health and Human Development's Maternal-Fetal Medicine Units Network. This secondary analysis was limited to emergent procedures, defined as those performed for cord prolapse, abruption, placenta previa with hemorrhage, nonreassuring fetal heart rate tracing, or uterine rupture. Incision-to-delivery intervals, incision-to-closure intervals, and maternal outcomes were compared by skin-incision type (transverse compared with vertical) after stratifying for primary compared with repeat singleton cesarean delivery. Neonatal outcomes were compared by skin-incision type.
RESULTS: Of the 37,112 live singleton cesarean deliveries, 3,525 (9.5%) were performed for emergent indications of which 2,498 (70.9%) were performed by transverse and the remaining 1,027 (29.1%) by vertical incision. Vertical skin incision shortened median incision-to-delivery intervals by 1 minute (3 compared with 4 minutes, P<.001) in primary and 2 minutes (3 compared with 5 minutes, P<.001) in repeat cesarean deliveries. Total median operative time was longer after vertical skin incision by 3 minutes in primary (46 compared with 43 minutes, P<.001) and 4 minutes in repeat cesarean deliveries (56 compared with 52 minutes, P<.001). Neonates delivered through a vertical incision were more likely to have an umbilical artery pH of less than 7.0 (10% compared with 7%, P=.02), to be intubated in the delivery room (17% compared with 13%, P=.001), or to be diagnosed with hypoxic ischemic encephalopathy (3% compared with 1%, P<.001).
CONCLUSION: In emergency cesarean deliveries, neonatal delivery occurred more quickly after a vertical skin incision, but this was not associated with improved neonatal outcomes. (Obstet Gynecol 2010; 115: 1134-40)
C1 Columbia Univ, Dept Obstet & Gynecol, New York, NY USA.
Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA.
Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA.
Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, Dallas, TX 75390 USA.
Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA.
Univ Pittsburgh, Dept Obstet & Gynecol, Pittsburgh, PA USA.
Wake Forest Univ Hlth Sci, Dept Obstet & Gynecol, Winston Salem, NC USA.
Thomas Jefferson Univ, Dept Obstet & Gynecol, Philadelphia, PA 19107 USA.
Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
Univ Cincinnati, Dept Obstet & Gynecol, Cincinnati, OH USA.
Univ Miami, Dept Obstet & Gynecol, Miami, FL USA.
Univ Tennessee, Dept Obstet & Gynecol, Memphis, TN 38103 USA.
Univ Texas San Antonio, Dept Obstet & Gynecol, San Antonio, TX USA.
George Washington Univ, Dept Obstet & Gynecol, Ctr Biostat, Washington, DC USA.
Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Wylie, BJ (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, 55 Fruit St, Boston, MA 02114 USA.
EM bwylie@partners.org
RI Varner, Michael/K-9890-2013
OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [HD21410, HD21414, HD27860, HD27861, HD27869, HD27905,
HD27915, HD27917, HD34116, HD34122, HD34136, HD34208, HD34210, HD36801];
National Institute of Child Health and Human Development (NICHD); NICHD
Maternal-Fetal Medicine Units Network; NIH-NICHD [HD-27905-05]; National
Heart, Lung and Blood Institute; National Institutes of Health
FX Supported by grants from the Eunice Kennedy Shriver National Institute
of Child Health and Human Development (HD21410, HD21414, HD27860,
HD27861, HD27869, HD27905, HD27915, HD27917, HD34116, HD34122, HD34136,
HD34208, HD34210, HD36801).; Dr. Landon received honoraria for doing
grand rounds at various institutions and travel and accommodation
expenses covered or reimbursed for grand rounds. Dr. Leveno received
royalties for the Williams Obstetrics textbook. Dr. Varner received
grants or grants pending from the National Institute of Child Health and
Human Development (NICHD) for research conducted with funding from the
NICHD Maternal-Fetal Medicine Units Network. Dr. Miodovnik received a
grant, NIH-NICHD HD-27905-05 (until 2003). Dr. O'Sullivan was reimbursed
for travel expenses related to this study by the NICHD; participated in
the data monitoring committee after no longer a member of the study
group and the compensation for travel and hotel was reimbursed by the
NICHD; received a grant or has grants pending from the National Heart,
Lung and Blood Institute for The Women's Health Initiative (WHI; The
National Children's Study, sponsored by the National Institutes of
Health); travel and accommodation expenses were reimbursed by NHLBI for
the WHI annual meeting. The other authors did not report any potential
conflicts of interest.
NR 9
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U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD JUN
PY 2010
VL 115
IS 6
BP 1134
EP 1140
DI 10.1097/AOG.0b013e3181df937f
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 603VD
UT WOS:000278235300006
PM 20502282
ER
PT J
AU Saleem, S
Rouse, DJ
McClure, EM
Zaidi, A
Reza, T
Yahya, Y
Memon, IA
Khan, NH
Memon, G
Soomro, N
Pasha, O
Wright, LL
Moore, J
Goldenberg, RL
AF Saleem, Sarah
Rouse, Dwight J.
McClure, Elizabeth M.
Zaidi, Anita
Reza, Tahira
Yahya, Y.
Memon, I. A.
Khan, N. H.
Memon, G.
Soomro, N.
Pasha, Omrana
Wright, Linda L.
Moore, Janet
Goldenberg, Robert L.
TI Chlorhexidine Vaginal and Infant Wipes to Reduce Perinatal Mortality and
Morbidity A Randomized Controlled Trial
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID CLINICAL-TRIAL; PERIPARTAL INFECTION; DEVELOPING-COUNTRIES;
NEONATAL-MORTALITY; SOUTHERN NEPAL; IRRIGATION; OUTCOMES; LABOR
AB OBJECTIVE: To estimate the effects of chlorhexidine vaginal and baby wipes on fetal and neonatal mortality, respectively, and infection-related morbidity.
METHODS: We performed a placebo-controlled, randomized trial of chlorhexidine vaginal and neonatal wipes to reduce neonatal sepsis and mortality in three hospitals in Pakistan. The primary study outcome was a composite of neonatal sepsis or 7-day perinatal mortality.
RESULTS: From 2005 to 2008, 5,008 laboring women and their neonates were randomly assigned to receive either chlorhexidine wipes (n = 2,505) or wipes with a saline placebo (n = 2,503). The primary outcome was similar in the chlorhexidine and control groups (3.1% compared with 3.4%; relative risk 0.91, 95% confidence interval 0.67-1.24) as was the composite rate of neonatal sepsis or 28-day perinatal mortality (3.8% compared with 3.9%, relative risk 0.96, 95% confidence interval 0.73-1.27). At day 7, the chlorhexidine group had a lower rate of neonatal skin infection (3.3% compared with 8.2%, P<.001). With the exception of less frequent 7-day hospitalization in the chlorhexidine group, there were no significant differences in maternal outcomes between the groups.
CONCLUSION: Using maternal chlorhexidine vaginal wipes during labor and neonatal chlorhexidine wipes does not reduce maternal and perinatal mortality or neonatal sepsis. The finding of reduced superficial skin infections on day 7 without change in sepsis or mortality suggests that this difference, although statistically significant, may not be of major importance.
C1 [Saleem, Sarah] Aga Khan Univ, Karachi, Pakistan.
Univ Alabama, Birmingham, AL USA.
RTI Int, Res Triangle Pk, NC USA.
Dow Univ Hlth Sci, Karachi, Pakistan.
Eunice Kennedy Shriver Natl Inst Child & Human De, Bethesda, MD USA.
Drexel Univ, Coll Med, Philadelphia, PA 19104 USA.
RP Saleem, S (reprint author), Aga Khan Univ, Karachi, Pakistan.
EM sarah.saleem@aku.edu
FU National Institute of Child Health and Human Development Global Network
for Women's and Children's Health Research [U01 HD040607, U01 HD040636];
Bill and Melinda Gates Foundation; Aga Khan University, Pharmacy
Department and Research Office; National Institute of Child Health and
Human Development
FX Funded by the National Institute of Child Health and Human Development
Global Network for Women's and Children's Health Research grants U01
HD040607 and U01 HD040636, the Bill and Melinda Gates Foundation, and
Aga Khan University, Pharmacy Department and Research Office.; S.
Saleem, E. M. McClure, and O. Pasha received support for travel to
meetings for the study from National Institute of Child Health and Human
Development. L. L. Wright received a gift for serving on the Faculty of
Medicine at Pigsty University. R. L. Goldenberg served on the
Unitedhealthcare Women's Advisory Group. The other authors did not
report any potential conflicts of interest.
NR 19
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Z9 23
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD JUN
PY 2010
VL 115
IS 6
BP 1225
EP 1232
DI 10.1097/AOG.0b013e3181e00ff0
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 603VD
UT WOS:000278235300018
PM 20502294
ER
PT J
AU Hofmann, JN
Keifer, MC
De Roos, AJ
Fenske, RA
Furlong, CE
van Belle, G
Checkoway, H
AF Hofmann, Jonathan N.
Keifer, Matthew C.
De Roos, Anneclaire J.
Fenske, Richard A.
Furlong, Clement E.
van Belle, Gerald
Checkoway, Harvey
TI Occupational determinants of serum cholinesterase inhibition among
organophosphate-exposed agricultural pesticide handlers in Washington
State
SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
LA English
DT Article
ID PROTECTIVE EQUIPMENT; DERMAL EXPOSURE; FARM-WORKERS; HEALTH;
APPLICATORS; CHLORPYRIFOS; PREDICTORS; CALIFORNIA; ALGORITHM; EXCRETION
AB Objective To identify potential risk factors for serum cholinesterase (BuChE) inhibition among agricultural pesticide handlers exposed to organophosphate (OP) and N-methyl-carbamate (CB) insecticides.
Methods We conducted a longitudinal study among 154 agricultural pesticide handlers who participated in the Washington State cholinesterase monitoring program in 2006 and 2007. BuChE inhibition was analysed in relation to reported exposures before and after adjustment for potential confounders using linear regression. ORs estimating the risk of BuChE depression (>20% from baseline) were also calculated for selected exposures based on unconditional logistic regression analyses.
Results An overall decrease in mean BuChE activity was observed among study participants at the time of followup testing during the OP/CB spray season relative to preseason baseline levels (mean decrease of 5.6%, p<0.001). Score for estimated cumulative exposure to OP/CB insecticides in the past 30 days was a significant predictor of BuChE inhibition (beta = -1.74, p<0.001). Several specific work practices and workplace conditions were associated with greater BuChE inhibition, including mixing/loading pesticides and cleaning spray equipment. Factors that were protective against BuChE inhibition included full-face respirator use, wearing chemical-resistant boots and storing personal protective equipment in a locker at work.
Conclusions Despite existing regulations, agricultural pesticide handlers continue to be exposed to OP/CB insecticides at levels resulting in BuChE inhibition. These findings suggest that modifying certain work practices could potentially reduce BuChE inhibition. Replication from other studies will be valuable.
C1 [Hofmann, Jonathan N.; De Roos, Anneclaire J.; Checkoway, Harvey] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Keifer, Matthew C.; Fenske, Richard A.; van Belle, Gerald; Checkoway, Harvey] Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA.
[De Roos, Anneclaire J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Furlong, Clement E.] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA.
[Furlong, Clement E.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[van Belle, Gerald] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
RP Hofmann, JN (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8109,MSC 7240, Bethesda, MD 20892 USA.
EM hofmannjn@mail.nih.gov
FU U.S. CDC/NIOSH [1 U50 OH07544, 1 T42 OH008433-01]; U.S. NIEHS [P30
ES07033, P42 ES04696, T32 ES07262]
FX Funding Financial support for this project was provided by U.S.
CDC/NIOSH grants #1 U50 OH07544 and #1 T42 OH008433-01, and U.S. NIEHS
grants #P30 ES07033, #P42 ES04696 and #T32 ES07262.
NR 40
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PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1351-0711
J9 OCCUP ENVIRON MED
JI Occup. Environ. Med.
PD JUN
PY 2010
VL 67
IS 6
BP 375
EP 386
DI 10.1136/oem.2009.046391
PG 12
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 605NI
UT WOS:000278353900005
PM 19819864
ER
PT J
AU Panda, P
Forooghian, F
Goodglick, T
Chan, CC
Nussenblatt, R
Sen, HN
AF Panda, Puneet
Forooghian, Farzin
Goodglick, Todd
Chan, Chi-Chao
Nussenblatt, Robert
Sen, H. Nida
TI Orbital Lymphoma Masquerading as Panuveitis
SO OCULAR IMMUNOLOGY AND INFLAMMATION
LA English
DT Article
DE MALT lymphoma; orbital MALT lymphoma; Rituximab; uveitis; masquerade
syndrome
ID UVEITIS
AB Purpose: To describe a case of orbital mucosa-associated lymphoid tissue (MALT) lymphoma masquerading as unilateral panuveitis.
Methods: Retrospective chart review.
Results: A 53-year-old female patient with unilateral vitritis and exudative retinal detachment refractory to immunosuppressive treatment was eventually diagnosed with orbital MALT lymphoma. Following treatment with radiotherapy and rituximab, the patient's intraocular inflammation and retinal detachment resolved.
Conclusions: Orbital MALT lymphoma can masquerade as refractory unilateral panuveitis with exudative retinal detachment and appears to respond to a combination of radiotherapy and specific B-cell-targeted systemic therapy.
C1 [Panda, Puneet; Forooghian, Farzin; Chan, Chi-Chao; Nussenblatt, Robert; Sen, H. Nida] NEI, NIH, Bethesda, MD 20892 USA.
[Goodglick, Todd] Washington Eye Phys & Surg, Bethesda, MD USA.
RP Sen, HN (reprint author), NEI, NIH, 10 Ctr Dr,Bldg 10,Rm 10N112, Bethesda, MD 20892 USA.
EM senh@nei.nih.gov
FU Clinical Research Training Program; NIH; Pfizer Inc.; National Eye
Institute
FX This research was made possible through the Clinical Research Training
Program, a public-private partnership supported jointly by the NIH and
Pfizer Inc. (grant to the Foundation for NIH from Pfizer Inc. (PP)) as
well as the Intramural Research Program of NIH, National Eye Institute
(PP, FF, CCC, RBN, HNS).
NR 5
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Z9 2
U1 0
U2 1
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA
SN 0927-3948
J9 OCUL IMMUNOL INFLAMM
JI Ocul. Immunol. Inflamm.
PD JUN
PY 2010
VL 18
IS 3
BP 181
EP 183
DI 10.3109/09273941003728947
PG 3
WC Ophthalmology
SC Ophthalmology
GA 612OT
UT WOS:000278910300007
PM 20482392
ER
PT J
AU Christen, WG
Glynn, RJ
Chew, EY
Buring, JE
AF Christen, William G.
Glynn, Robert J.
Chew, Emily Y.
Buring, Julie E.
TI Vitamin E and Age-Related Macular Degeneration in a Randomized Trial of
Women
SO OPHTHALMOLOGY
LA English
DT Article
ID BEAVER DAM EYE; SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; BETA-CAROTENE
SUPPLEMENTATION; LOW-DOSE ASPIRIN; PRIMARY PREVENTION;
CARDIOVASCULAR-DISEASE; CLINICAL-TRIALS; LASER PHOTOCOAGULATION;
PHOTODYNAMIC THERAPY; DIETARY ANTIOXIDANTS
AB Objective: To test whether alternate day vitamin E affects the incidence of age-related macular degeneration (AMD) in a large-scale randomized trial of women.
Design: Randomized, double-masked, placebo-controlled trial.
Participants: Thirty-nine thousand eight hundred seventy-six apparently healthy female health professionals aged 45 years or older.
Intervention: Participants were assigned randomly to receive either 600 IU of natural-source vitamin E on alternate days or placebo.
Main Outcome Measures: Incident AMD responsible for a reduction in best-corrected visual acuity to 20/30 or worse based on self-report confirmed by medical record review.
Results: After 10 years of treatment and follow-up, there were 117 cases of AMD in the vitamin E group and 128 cases in the placebo group (relative risk, 0.93; 95% confidence interval, 0.72-1.19).
Conclusions: In a large-scale randomized trial of female health professionals, long-term alternate-day use of 600 IU of natural-source vitamin E had no large beneficial or harmful effect on risk of AMD.
C1 [Christen, William G.; Glynn, Robert J.; Buring, Julie E.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA.
[Glynn, Robert J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Buring, Julie E.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA.
[Chew, Emily Y.] NEI, Bethesda, MD 20892 USA.
RP Christen, WG (reprint author), 900 Commonwealth Ave E, Boston, MA 02215 USA.
EM wchristen@rics.bwh.harvard.edu
FU Astra Zeneca; National Institutes of Health, Bethesda, Maryland [CA
47988, HL 43851, EY 06633]
FX Dr. Glynn received a grant from Astra Zeneca.; Supported by the National
Institutes of Health, Bethesda, Maryland (grant nos.: CA 47988, HL
43851, and EY 06633). Pills and packaging were provided by Bayer
Healthcare and the Natural Source Vitamin E Association. Bayer
Healthcare and the Natural Source Vitamin E Association had no role in
the design and conduct of the study; in the collection, analysis, and
interpretation of the data; or in the preparation, review, or approval
of the manuscript.
NR 38
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Z9 11
U1 1
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD JUN
PY 2010
VL 117
IS 6
BP 1163
EP 1168
DI 10.1016/j.ophtha.2009.10.043
PG 6
WC Ophthalmology
SC Ophthalmology
GA 603QZ
UT WOS:000278224400011
PM 20153900
ER
PT J
AU Bates, BD
Mitchell, K
Keller, JM
Chan, CC
Swaim, WD
Yaskovich, R
Mannes, AJ
Iadarola, MJ
AF Bates, Brian D.
Mitchell, Kendall
Keller, Jason M.
Chan, Chi-Chao
Swaim, William D.
Yaskovich, Ruth
Mannes, Andrew J.
Iadarola, Michael J.
TI Prolonged analgesic response of cornea to topical resiniferatoxin, a
potent TRPV1 agonist
SO PAIN
LA English
DT Article
DE Resiniferatoxin; Vanilloid receptor 1; C-fibers; Wound healing; TRPV1;
Eye wipe test; Corneal pain; Ophthalmic analgesia; CGRP
ID VANILLOID RECEPTOR-1; NEURONS; PAIN; CAPSAICIN; CELLS; INNERVATION;
KERATECTOMY; MORPHOLOGY; MEMBRANE; DELETION
AB Analgesics currently available for the treatment of pain following ophthalmic surgery or injury are limited by transient effectiveness and undesirable or adverse side effects. The cornea is primarily innervated by small-diameter C-fiber sensory neurons expressing TRPV1 (transient receptor potential channel, subfamily V, member 1), a sodium/calcium cation channel expressed abundantly by nociceptive neurons and consequently a target for pain control. Resiniferatoxin (RTX), a potent TRPV1 agonist, produces transient analgesia when injected peripherally by inactivating TRPV1-expressing nerve terminals through excessive calcium influx. The aim of the present study was to evaluate topical RTX as a corneal analgesic. In rat cornea, a single application of RTX dose dependently eliminated or reduced the capsaicin eye wipe response for 3-5 days, with normal nociceptive responses returning by 5-7 days. RTX alone produced a brief but intense noxious response, similar to capsaicin, necessitating pretreatment of the cornea with a local anesthetic. Topical lidocaine, applied prior to RTX, blocks acute nociceptive responses to RTX without impairing the subsequent analgesic effect. Importantly, RTX analgesia (a) did not impair epithelial wound healing, (b) left the blink reflex intact and (c) occurred without detectable histological damage to the cornea. Immunohistochemistry showed that loss of CGRP immunoreactivity, a surrogate marker for TRPV1-expressing fibers, extended at least to the corneal-scleral boundary and displayed a progressive return, coincident with the return of capsaicin sensitivity. These data suggest that RTX may be a safe and effective treatment for post-operative or post-injury ophthalmic pain. Published by Elsevier B. V. on behalf of International Association for the Study of Pain.
C1 [Chan, Chi-Chao] NEI, Immunopathol Sect, NIH, Bethesda, MD 20982 USA.
[Bates, Brian D.; Mitchell, Kendall; Keller, Jason M.; Yaskovich, Ruth; Mannes, Andrew J.; Iadarola, Michael J.] Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, NIH, Bethesda, MD 20982 USA.
[Swaim, William D.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20982 USA.
[Mannes, Andrew J.; Iadarola, Michael J.] NIH, Div Anesthesia & Surg Serv, Ctr Clin, Bethesda, MD 20982 USA.
RP Iadarola, MJ (reprint author), Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, NIH, Bldg 49,Room 1C20,49 Convent Dr,MSC-4410, Bethesda, MD 20892 USA.
EM miadarola@dir.nidcr.nih.gov
OI Mannes, Andrew/0000-0001-5834-5667
FU Division of Intramural Research, NIDCR
FX This research was supported by the Division of Intramural Research,
NIDCR. We thank Dr. Rachel Bishop, National Eye Institute, for her
helpful discussion.
NR 32
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U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
J9 PAIN
JI Pain
PD JUN
PY 2010
VL 149
IS 3
BP 522
EP 528
DI 10.1016/j.pain.2010.03.024
PG 7
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 598AS
UT WOS:000277804700020
PM 20403666
ER
PT J
AU Gonzalez-Miguel, J
Rosario, L
Rota-Nodari, E
Morchon, R
Simon, F
AF Gonzalez-Miguel, Javier
Rosario, Luis
Rota-Nodari, Elena
Morchon, Rodrigo
Simon, Fernando
TI Identification of immunoreactive proteins of Dirofilaria immitis and D.
repens recognized by sera from patients with pulmonary and subcutaneous
dirofilariosis
SO PARASITOLOGY INTERNATIONAL
LA English
DT Article
DE Dirofilaria immitis; Dirofilaria repens; Humans; Mass spectrometry;
Soluble proteome
ID EXCRETORY-SECRETORY PRODUCTS; PLASMINOGEN-BINDING PROTEIN; HEAT-SHOCK
PROTEINS; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE;
CAENORHABDITIS-ELEGANS; LACTATE-DEHYDROGENASE; ONCHOCERCA-VOLVULUS;
BRUGIA-MALAYI; MOLECULAR CHAPERONES; ECHINOSTOMA-CAPRONI
AB Human pulmonary and subcutaneous dirofilariosis caused by Dirofilaria immitis and Dirofilaria repens are worldwide diagnosed with increasing frequency. These species are responsible for the development of benign pulmonary and subcutaneous nodules, respectively, that can be confused with lung or cutaneous cancer. The aim of the present work was to identify D. immitis and D. repens proteins differentially recognized by serum samples from individuals with human pulmonary and subcutaneous dirofilariosis, using two-dimensional electrophoresis and mass spectrometry. Twenty-three immunoreactive proteins of D. immitis and 15 of D. repens were identified. The results point to the existence of differential antigenic recognition in each species, both in the number and type of proteins recognized. Individuals with pulmonary dirofilariosis recognized, on the proteome of D. immitis, among others, different isoforms of 6 enzymes involved in glycolysis, 3 redox-related proteins with antioxidant capacity and 3 heat shock proteins. Individuals with subcutaneous dirofilariosis recognized on the proteome of D. repens only 3 glycolytic enzymes, one protein involved in redox processes and one heat shock protein. These data suggest that in cases of pulmonary dirofilariosis there exists a wider recognition of immunoreactive D. immitis proteins related to key survival processes, such as energy generation, the struggle against oxidative stress and molecular repair, than in cases of human subcutaneous dirofilariosis against D. repens. This could contribute to explain the differences described in the capacity of D. immitis and D. repens development and in the frequency of occurrence of pulmonary and subcutaneous dirofilariosis in the human host. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
C1 [Gonzalez-Miguel, Javier; Rosario, Luis; Rota-Nodari, Elena; Morchon, Rodrigo; Simon, Fernando] Univ Salamanca, Parasitol Lab, Fac Pharm, Salamanca 37007, Spain.
[Rosario, Luis] Univ Puerto Rico, Sch Med, NIH MIRT Fogarty Int Ctr Program, San Juan, PR 00936 USA.
[Rota-Nodari, Elena] Univ Milan, Leonardo Vinci Program, Milan, Italy.
RP Simon, F (reprint author), Univ Salamanca, Parasitol Lab, Fac Pharm, Avda Campo Charro S-N, Salamanca 37007, Spain.
EM fersimon@usal.es
RI IBSAL, Secretaria/H-3719-2011;
OI Rosario, Luis/0000-0003-0014-1543; Gonzalez-Miguel,
Javier/0000-0003-4279-4761
FU Agenda de Desarrollo Economic de Castilla y Leon; Junta de Castilla y
Leon, Spain [SA090/A09]
FX We thank Dr. L Venco (Clinica Veterinaria Citta di Pavia) who provided
us D. immitis and D. repens adult worms, and Drs. P. Lammie and V.
Kartashev for serum samples from individuals diagnosed as having
pulmonary and subcutaneous dirofilariosis, respectively. This research
was supported by Agenda de Desarrollo Economic de Castilla y Leon
(cofinanced with FEDER funds), Junta de Castilla y Leon (grant
SA090/A09), Spain.
NR 64
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Z9 7
U1 0
U2 2
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1383-5769
J9 PARASITOL INT
JI Parasitol. Int.
PD JUN
PY 2010
VL 59
IS 2
BP 248
EP 256
DI 10.1016/j.parint.2010.02.010
PG 9
WC Parasitology
SC Parasitology
GA 663EW
UT WOS:000282866800022
PM 20197111
ER
PT J
AU Rochowski, A
Sun, CX
Glogauer, M
Alter, B
AF Rochowski, Andrzej
Sun, Chunxiang
Glogauer, Michael
Alter, Blanche
TI NEUTROPHIL FUNCTION IN PATIENTS WITH INHERITED BONE MARROW FAILURE
SYNDROMES
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Rochowski, Andrzej; Sun, Chunxiang; Glogauer, Michael; Alter, Blanche] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JUN
PY 2010
VL 54
IS 6
BP 800
EP 800
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 578JT
UT WOS:000276290300050
ER
PT J
AU Rao, VK
Price, S
Davis, J
Perkins, K
Gill, F
Pittaluga, S
Fleisher, T
Jaffe, E
AF Rao, V. Koneti
Price, Susan
Davis, Joie
Perkins, Katie
Gill, Fred
Pittaluga, Stefania
Fleisher, Thomas
Jaffe, Elaine
TI DEVELOPMENT OF LYMPHOMAS IN FAMILIES WITH AUTOIMMUNE LYMPHOPROLIFERATIVE
SYNDROME (ALPS)
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Rao, V. Koneti; Price, Susan; Davis, Joie; Perkins, Katie; Gill, Fred; Pittaluga, Stefania; Fleisher, Thomas; Jaffe, Elaine] NIH, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JUN
PY 2010
VL 54
IS 6
BP 813
EP 813
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 578JT
UT WOS:000276290300094
ER
PT J
AU Badgett, T
Guo, XA
Wei, J
Song, Y
Tolman, C
Yeh, S
Chen, QR
Johansson, P
Wen, XY
He, JB
Beckstead, W
Khan, J
AF Badgett, Tom
Guo, Xiang
Wei, Jun
Song, Young
Tolman, Catherine
Yeh, Susan
Chen, Qingrong
Johansson, Peter
Wen, Xinyu
He, Jianbin
Beckstead, Wesley
Khan, Javed
TI NEXT GENERATION SEQUENCING OF THE NEUROBLASTOMA TRANSCRIPTOME IDENTIFIES
MULTIPLE PROTEIN DISRUPTING MUTATIONS
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Badgett, Tom; Guo, Xiang; Wei, Jun; Song, Young; Tolman, Catherine; Yeh, Susan; Chen, Qingrong; Johansson, Peter; Wen, Xinyu; He, Jianbin; Beckstead, Wesley; Khan, Javed] NCI, Bethesda, MD 20892 USA.
RI Khan, Javed/P-9157-2014
OI Khan, Javed/0000-0002-5858-0488
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JUN
PY 2010
VL 54
IS 6
BP 841
EP 841
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 578JT
UT WOS:000276290300193
ER
PT J
AU Cunningham, CK
Rudy, BJ
Xu, JH
Bethel, J
Kapogiannis, BG
Ahmad, S
Wilson, CM
Flynn, PM
AF Cunningham, Coleen K.
Rudy, Bret J.
Xu, Jiahong
Bethel, James
Kapogiannis, Bill G.
Ahmad, Sushma
Wilson, Craig M.
Flynn, Patricia M.
CA Adolescent Med Trials Network HIV
TI Randomized Trial to Determine Safety and Immunogenicity of Two
Strategies for Hepatitis B Vaccination in Healthy Urban Adolescents in
the United States
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Article
DE adolescents; hepatitis B; vaccination; immunogenicity
ID HOMOSEXUAL MEN; EFFICACY; CHILDREN; 2-DOSE; ADULTS
AB Background: Multiple studies have shown excellent response rates after hepatitis B immunization in youth; however, one previous study conducted in urban youth demonstrated poor responses.
Methods: Urban youth, ages 12 to 17 years, at participating Adolescent Medicine Trials Network for HIV/AIDS Interventions Clinical/Research sites were randomized to receive either 2 doses of Recombivax HB (10 mu g hepatitis B surface antigen) or Twinrix (20 mu g hepatitis B surface antigen and 720 EL.U hepatitis A antigen) at 0 and 24 weeks. Safety data were collected and antibody measures performed at 0, 28, and 76 weeks.
Results: A total of 123 subjects were enrolled and 102 had week 28 serum samples available for antibody measure. A positive response (serum antibody >= 10 mIU/mL) to hepatitis B antigen was documented in 41 of 47 (87.2%; 95% confidence interval [CI] 74.3%-95.2%) Recombivax HB recipients and in 52 of 55 (94.6%; 95% CI, 84.9%-98.9%) Twinrix recipients (P = 0.295). In an adjusted analysis, those identified as Hispanic ethnicity (N = 86) were more likely to have a positive response (odds ratio 7.38, 95% CI, 1.56-34.95; P = 0.0018); whereas those who identified as not heterosexual (N = 9) were less likely to respond (odds ratio = 0.12, 95% CI, 0.02-0.74). The majority of youth in the Twinrix arm were hepatitis A antibody positive at baseline (26/51; 51%); however, 24 of 25 hepatitis A antibody negative youth responded to the hepatitis A component. Both vaccines were safe.
Conclusions: Response rate to 2 doses of Recombivax HB in urban youth is lower than previous studies suggest. The factors associated with diminished response are not known.
C1 [Cunningham, Coleen K.] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA.
[Rudy, Bret J.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA.
[Kapogiannis, Bill G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD USA.
[Wilson, Craig M.] UAB, Dept Epidemiol & Pediat, Birmingham, AL USA.
[Flynn, Patricia M.] St Jude Childrens Hosp, Dept Infect Dis, Memphis, TN 38105 USA.
[Xu, Jiahong; Bethel, James; Ahmad, Sushma] WESTAT Corp, Rockville, MD 20850 USA.
RP Cunningham, CK (reprint author), Duke Univ, Med Ctr, Dept Pediat, Box 3499,Erwin Ave, Durham, NC 27710 USA.
EM coleen.cunningham@duke.edu
FU National Institutes of Health through the Eunice Kennedy Shriver
National Institute of Child Health and Human Development [U01 HD 040533,
U01 HD 040474]; National Institutes on Drug Abuse and Mental Health;
National Center for Research Resources, National Institutes of Health;
Department of Health and Human Services; Children's National Medical
Center [M01RR020359]; Tulane University/Louisiana State University
[M01RR05096]; University of California at San Francisco [M01RR00083-42];
Pediatric Clinical Research Grant [M01RR01271]
FX Supported by The Adolescent Medicine Trials Network for HIV/AIDS
Interventions (ATN) from the National Institutes of Health (U01 HD
040533 and U01 HD 040474) through the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (B. Kapogiannis, R.
Hazra, S. Lee, C. Worrell), with supplemental funding from the National
Institutes on Drug Abuse (N. Borek) and Mental Health (P. Brouwers, S.
Allison). Additional support for this study was provided by grants from
the General Clinical Research Center (GCRC) Program of the National
Center for Research Resources, National Institutes of Health, and
Department of Health and Human Services. The following grants provided
support: Children's National Medical Center, GCRC Grant M01RR020359;
Tulane University/Louisiana State University, GCRC Grant M01RR05096; and
University of California at San Francisco, GCRC Grant M01RR00083-42 and
Pediatric Clinical Research Grant M01RR01271.
NR 22
TC 4
Z9 4
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0891-3668
J9 PEDIATR INFECT DIS J
JI Pediatr. Infect. Dis. J.
PD JUN
PY 2010
VL 29
IS 6
BP 530
EP 534
DI 10.1097/INF.0b013e3181d285c7
PG 5
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA 605UK
UT WOS:000278372300010
PM 20173677
ER
PT J
AU Zhang, Q
Fu, HJ
Pan, J
He, J
Ryota, S
Hara, Y
Wang, Y
Lubet, RA
You, M
AF Zhang, Qi
Fu, Huijing
Pan, Jing
He, Jun
Ryota, Seto
Hara, Yukihiko
Wang, Yian
Lubet, Ronald A.
You, Ming
TI Effect of Dietary Polyphenon E and EGCG on Lung Tumorigenesis in A/J
Mice
SO PHARMACEUTICAL RESEARCH
LA English
DT Article
DE chemoprevention; degradation; EGCG; lung tumorigenesis; polyphenon E
ID GREEN TEA; (-)-EPIGALLOCATECHIN GALLATE; EPIGALLOCATECHIN GALLATE;
CANCER CHEMOPREVENTION; TUMOR PROGRESSION; CARCINOGENESIS; INHIBITION;
APOPTOSIS; PULMONARY; CATECHINS
AB To compare the chemopreventive efficacy of Polyphenon E (Poly E), (-)-epigallocatechin-3-gallate (EGCG) and Polyphenon E without EGCG (Poly E-EGCG) on the development of benzo(a)pyrene (B(a)P)-induced lung tumors in A/J mice.
Female A/J mice were given a single intraperitoneal injection of B(a)P (100 mg/kg body weight). One week after B(a)P injection, animals received AIN-76A purified powder diet containing 0.975% (wt/wt) EGCG, 0.525% (wt/wt) Poly E-EGCG or 1.5% (wt/wt) Poly E for 24 weeks or control diet with no additives.
Poly E treatment significantly decreased tumor multiplicity by 52% and tumor load by 64%, while EGCG and Poly E-EGCG did not significantly inhibit lung tumor multiplicity. EGCG was more stable in a complex mixture (Poly E) than as a pure compound.
EGCG was ineffective when administered by diet likely due to its instability. Thus, EGCG's efficacy on mice lung tumorigenesis requires the presence of other tea catechins.
C1 [Zhang, Qi; Pan, Jing; He, Jun; Wang, Yian; You, Ming] Washington Univ, Dept Surg, St Louis, MO 63110 USA.
[Zhang, Qi; Pan, Jing; He, Jun; Wang, Yian; You, Ming] Washington Univ, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA.
[Fu, Huijing] Washington Univ, Dept Energy Environm & Chem Engn, St Louis, MO 63130 USA.
[Ryota, Seto; Hara, Yukihiko] Mitsui Norin Co Ltd, Shizuoka 42601, Japan.
[Lubet, Ronald A.] NCI, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA.
RP You, M (reprint author), Washington Univ, Dept Surg, 660 S Euclid Ave,Campus Box 8109, St Louis, MO 63110 USA.
EM youm@msnotes.wustl.edu
FU NIH [R01CA139959]
FX This work was supported by NIH Grant R01CA139959 (Wang & You).
NR 25
TC 16
Z9 21
U1 1
U2 4
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0724-8741
J9 PHARM RES-DORDR
JI Pharm. Res.
PD JUN
PY 2010
VL 27
IS 6
BP 1066
EP 1071
DI 10.1007/s11095-010-0056-3
PG 6
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 597VW
UT WOS:000277791300013
PM 20112129
ER
PT J
AU Deeken, JF
Cormier, T
Price, DK
Sissung, TM
Steinberg, SM
Tran, K
Liewehr, DJ
Dahut, WL
Miao, X
Figg, WD
AF Deeken, J. F.
Cormier, T.
Price, D. K.
Sissung, T. M.
Steinberg, S. M.
Tran, K.
Liewehr, D. J.
Dahut, W. L.
Miao, X.
Figg, W. D.
TI A pharmacogenetic study of docetaxel and thalidomide in patients with
castration-resistant prostate cancer using the DMET genotyping platform
SO PHARMACOGENOMICS JOURNAL
LA English
DT Article
DE pharmacogenomics; docetaxel; thalidomide; prostate cancer
ID SINGLE-NUCLEOTIDE POLYMORPHISMS; POPULATION PHARMACOKINETICS; CYTOSOLIC
SULFOTRANSFERASES; INTERINDIVIDUAL VARIABILITY; CYTOCHROME-P450 3A4;
SPASTIC PARAPLEGIA; DRUG DISPOSITION; SKELETAL-MUSCLE; BREAST-CANCER;
PPAR-DELTA
AB The anticancer agent docetaxel shows significant inter-individual variation in its pharmacokinetic and toxicity profile. Thalidomide is an active anticancer agent and also shows wide pharmacological variation. Past pharmacogenetic research has not explained this variation. Patients with prostate cancer enrolled in a randomized phase II trial using docetaxel and thalidomide versus docetaxel alone were genotyped using the Affymetrix DMET 1.0 platform, which tests for 1256 genetic variations in 170 drug disposition genes. Genetic polymorphisms were analyzed for associations with clinical response and toxicity. In all, 10 single-nucleotide polymorphisms (SNPs) in three genes were potentially associated with response to therapy: peroxisome proliferator-activated receptor-delta (PPAR-delta), sulfotransferase family, cytosolic, 1C, member 2 (SULT1C2) and carbohydrate (chondroitin 6) sulfotransferase 3 (CHST3). In addition, 11 SNPs in eight genes were associated with toxicities to treatment: spastic paraplegia 7 (pure and complicated autosomal recessive) (SPG7), CHST3, cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6), N-acetyltransferase 2 (arylamine N-acetyltransferase) (NAT2), ATP-binding cassette, sub-family C (CFTR/MRP), member 6 (ABCC6), ATPase, Cu + + transporting, alpha polypeptide (ATP7A), cytochrome P450, family 4, subfamily B, polypeptide 1 (CYP4B1) and solute carrier family 10 (sodium/bile acid cotransporter family), member 2 (SLC10A2). Genotyping results between drug metabolizing enzymes and transporters (DMET) and direct sequencing showed >96% of concordance. These findings highlight the role that non-CYP450 metabolizing enzymes and transporters may have in the pharmacology of docetaxel and thalidomide. The Pharmacogenomics Journal (2010) 10, 191-199; doi:10.1038/tpj.2009.57; published online 29 December 2009
C1 [Deeken, J. F.] Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Washington, DC 20007 USA.
[Cormier, T.; Tran, K.; Miao, X.] Affymetrix Inc, Santa Clara, CA USA.
[Price, D. K.; Sissung, T. M.; Dahut, W. L.; Figg, W. D.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Steinberg, S. M.; Liewehr, D. J.] NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA.
RP Deeken, JF (reprint author), Georgetown Univ, Med Ctr, Lombardi Canc Ctr, 3800 Reservoir Rd NW, Washington, DC 20007 USA.
EM deekenj@georgetown.edu
RI Figg Sr, William/M-2411-2016
FU NIH, National Cancer Institute, Center for Cancer Research, Bethesda,
MD, USA
FX This work was supported, in part, by the Intramural Research Program of
the NIH, National Cancer Institute, Center for Cancer Research,
Bethesda, MD, USA. Partial findings contained in this article were
initially presented at the 2007 Annual Convention of the American
Society of Clinical Oncology.
NR 61
TC 36
Z9 37
U1 2
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1470-269X
J9 PHARMACOGENOMICS J
JI Pharmacogenomics J.
PD JUN
PY 2010
VL 10
IS 3
BP 191
EP 199
DI 10.1038/tpj.2009.57
PG 9
WC Genetics & Heredity; Pharmacology & Pharmacy
SC Genetics & Heredity; Pharmacology & Pharmacy
GA 599VG
UT WOS:000277941300004
PM 20038957
ER
PT J
AU Bloom, MS
Houston, AS
Mills, JL
Molloy, CA
Hediger, ML
AF Bloom, Michael S.
Houston, Allison S.
Mills, James L.
Molloy, Cynthia A.
Hediger, Mary L.
TI Finger bone immaturity and 2D:4D ratio measurement error in the
assessment of the hyperandrogenic hypothesis for the etiology of autism
spectrum disorders
SO PHYSIOLOGY & BEHAVIOR
LA English
DT Article
DE Autism spectrum disorder; Digit ratio; Hyperandrogenic hypothesis;
Measurement error
ID 4TH DIGIT RATIO; ETHNIC-DIFFERENCES; RELATIVE LENGTHS; 4TH-DIGIT RATIO;
SEX-DIFFERENCES; 2ND; TESTOSTERONE; 2ND-DIGIT; CHILDREN; MALES
AB Emerging hypotheses suggest a causal role for prenatal androgen exposure in some cases of autism spectrum disorders (ASD). The ratios of the lengths of the bones of the 2nd to the 4th digit (2D:4D) are purported to be markers for prenatal androgen exposure and to be established early in gestation. Elongation of the 4th digit in response to testosterone is said to reduce 2D:4D in males versus females. We examined the ratios of bones from the left hand radiographs of 75 boys and 6 girls 4-8 years of age, diagnosed with ASD, to evaluate digit ratio as a marker for gestational androgen exposure. Contrary to our expectations, girls had reduced 2D:4D compared to boys but the difference was not significant (Cohen's D 0.51-0.66, P > 0.05). The limited sample size for this study and the absence of a referent group precluded providing robust estimates for girls and identifying possible statistical differences between the sexes. Tanner-Whitehouse 3 (TW3) rating of finger bone growth suggested relative immaturity of the 4th relative to the 2nd digits. Positive correlations were detected for 2D:4D ratios, body mass index (r = 0.23, P = 0.039), chronologic age (r = 0.35, P = 0.001), and skeletal age (r = 0.42, P < 0.0001). The TW3 ratings and associations between 2D:4D ratios and indicators of growth suggest that digits develop at different rates. This asynchronous development may produce differences in 2D:4D over time which could lead to erroneous interpretation of androgen exposure in utero among young ASD children. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Bloom, Michael S.] SUNY Albany, Dept Environm Hlth Sci, Rensselaer, NY 12214 USA.
[Houston, Allison S.] SUNY Albany, Dept Epidemiol & Biostat, Rensselaer, NY 12214 USA.
[Mills, James L.; Hediger, Mary L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA.
[Molloy, Cynthia A.] Cincinnati Childrens Hosp, Div Neurol, Med Ctr, Cincinnati, OH 45229 USA.
RP Bloom, MS (reprint author), Sch Publ Hlth, Dept Environm Hlth Sci, Rm 153,1 Univ Pl, Rensselaer, NY 12144 USA.
EM mbloom@albany.edu
OI Bloom, Michael/0000-0002-0028-5494
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development Intramural [Z01 HD008742]; National Institutes of Health
[M01 RR08084]
FX This research was funded by the Eunice Kennedy Shriver National
Institute of Child Health and Human Development Intramural funding
program (Z01 HD008742) and the National Institutes of Health (M01
RR08084). We acknowledge the substantial contributions of Daniel A.
Warren, who measured the radiographs as part of his student internship
at the NICHD, Scott C. Bello, MD, for critical review of this manuscript
at the early stages, and Mark Brasington, who was responsible for all
aspects of data collection at the Cincinnati Children's Hospital Medical
Center.
NR 32
TC 12
Z9 12
U1 2
U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0031-9384
J9 PHYSIOL BEHAV
JI Physiol. Behav.
PD JUN 1
PY 2010
VL 100
IS 3
SI SI
BP 221
EP 224
DI 10.1016/j.physbeh.2010.01.005
PG 4
WC Psychology, Biological; Behavioral Sciences
SC Psychology; Behavioral Sciences
GA 603EW
UT WOS:000278192400006
PM 20093135
ER
PT J
AU Llaneza, DC
DeLuke, SV
Batista, M
Crawley, JN
Christodulu, KV
Frye, CA
AF Llaneza, Danielle C.
DeLuke, Susan V.
Batista, Myra
Crawley, Jacqueline N.
Christodulu, Kristin V.
Frye, Cheryl A.
TI Communication, interventions, and scientific advances in autism: A
commentary
SO PHYSIOLOGY & BEHAVIOR
LA English
DT Editorial Material
DE Autism spectrum disorders; Social; Communication; Language; Gender
differences; Behavior modeling; Picture Exchange Communication System;
Mice; Genetics; BTBR; Center for Autism and Related Disabilities;
Education programs; Translational research
ID HIGH-FUNCTIONING AUTISM; TUBEROUS SCLEROSIS COMPLEX; SOCIAL APPROACH
BEHAVIORS; BTBR-T+TF/J MICE; SPECTRUM DISORDERS; RISK-FACTORS; CANDIDATE
GENES; GENOMIC SCREEN; MOLECULAR-GENETICS; ASPERGERS-DISORDER
AB Autism spectrum disorders (ASD) affect approximately 1 in 150 children across the U.S., and are characterized by abnormal social actions, language difficulties, repetitive or restrictive behaviors, and special interests. ASD include autism (autistic disorder), Asperger Syndrome, and Pervasive Developmental Disorder not otherwise specified (PDD-NOS or atypical autism). High-functioning individuals may communicate with moderate-to-high language skills, although difficulties in social skills may result in communication deficits. Low-functioning individuals may have severe deficiencies in language, resulting in poor communication between the individual and others. Behavioral intervention programs have been developed for ASD, and are frequently adjusted to accommodate specific individual needs. Many of these programs are school-based and aim to support the child in the development of their skills, for use outside the classroom with family and friends. Strides are being made in understanding the factors contributing to the development of ASD, particularly the genetic contributions that may underlie these disorders. Mutant mouse models provide powerful research tools to investigate the genetic factors associated with ASD and its comorbid disorders. In support, the BTBR T+tf/J mouse strain incorporates ASD-like social and communication deficits and high levels of repetitive behaviors. This commentary briefly reviews the reciprocal relationship between observations made during evidence-based behavioral interventions of high- versus low-functioning children with ASD and the accumulating body of research in autism, including animal studies and basic research models. This reciprocity is one of the hallmarks of the scientific method, such that research may inform behavioral treatments, and observations made during treatment may inform subsequent research. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Llaneza, Danielle C.; Frye, Cheryl A.] SUNY Albany, Dept Psychol, Albany, NY 12222 USA.
[DeLuke, Susan V.] Coll St Rose, Dept Literacy & Special Educ, Albany, NY USA.
[Batista, Myra] Kevin G Langan Sch, Ctr Disabil Serv, Albany, NY USA.
[Crawley, Jacqueline N.] NIMH, Intramural Res Program, Lab Behav Neurosci, Bethesda, MD 20892 USA.
[Christodulu, Kristin V.] SUNY Albany, Ctr Autism & Related Disabil, Albany, NY 12222 USA.
[Frye, Cheryl A.] SUNY Albany, Dept Biol, Albany, NY 12222 USA.
[Frye, Cheryl A.] SUNY Albany, Ctr Life Sci, Albany, NY 12222 USA.
RP Frye, CA (reprint author), SUNY Albany, Dept Psychol, Life Sci Room 1058, Albany, NY 12222 USA.
EM cafrye@albany.edu
FU NIMH NIH HHS [R01 MH067698, R01 MH067698-01A2, R01 MH067698-02, R01
MH067698-03, R01 MH067698-04, R01 MH067698-05, R01 MH067698-05S1]
NR 148
TC 11
Z9 12
U1 7
U2 23
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0031-9384
J9 PHYSIOL BEHAV
JI Physiol. Behav.
PD JUN 1
PY 2010
VL 100
IS 3
SI SI
BP 268
EP 276
DI 10.1016/j.physbeh.2010.01.003
PG 9
WC Psychology, Biological; Behavioral Sciences
SC Psychology; Behavioral Sciences
GA 603EW
UT WOS:000278192400014
PM 20093134
ER
PT J
AU Lewis, P
AF Lewis, P.
TI Dual use research in the life sciences
SO PHYTOPATHOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Phytopathological-Society (APS)
CY AUG 07-11, 2010
CL Charlotte, NC
SP Amer Phytopathol Soc
C1 [Lewis, P.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER PHYTOPATHOLOGICAL SOC
PI ST PAUL
PA 3340 PILOT KNOB ROAD, ST PAUL, MN 55121 USA
SN 0031-949X
J9 PHYTOPATHOLOGY
JI Phytopathology
PD JUN
PY 2010
VL 100
IS 6
SU S
BP S70
EP S70
PG 1
WC Plant Sciences
SC Plant Sciences
GA 822JU
UT WOS:000295042000413
ER
PT J
AU Wen, B
Chen, Y
Li, HR
Wang, J
Shen, J
Ma, AB
Qu, J
Bismuth, K
Debbache, J
Arnheiter, H
Hou, L
AF Wen, Bin
Chen, Yu
Li, Huirong
Wang, Jing
Shen, Jie
Ma, Aobo
Qu, Jia
Bismuth, Keren
Debbache, Julien
Arnheiter, Heinz
Hou, Ling
TI Allele-specific genetic interactions between Mitf and Kit affect
melanocyte development
SO PIGMENT CELL & MELANOMA RESEARCH
LA English
DT Article
DE transcription factor; signaling; gene interactions; pigmentation; mouse
ID MOUSE MICROPHTHALMIA LOCUS; CREST-DERIVED MELANOCYTE; ENDOTHELIN
RECEPTOR-B; C-KIT; WAARDENBURG-SYNDROME; TRANSCRIPTION; PIGMENTATION;
LINEAGE; SOX10; MICE
AB P>The tyrosine kinase receptor KIT and the transcription factor MITF, each required for melanocyte development, have been shown to interact functionally both in vitro and in vivo. In vitro, KIT signaling leads to MITF phosphorylation, affecting MITF activity and stability. In vivo, the presence of the Mitf Mi-wh allele exacerbates the spotting phenotype associated with heterozygosity for Kit mutations. Here, we show that among a series of other Mitf alleles, only the recessive Mitf mi-bws mimics the effect of Mitf Mi-wh on Kit. Intriguingly, Mitf mi-bws is characterized by a splice defect that leads to a reduction of RNAs containing MITF exon 2B which encodes serine-73, a serine phosphorylated upon KIT signaling. Nevertheless, other Mitf alleles that generally affect Mitf RNA levels, or carry a serine-73-to-alanine mutation that specifically reduces exon 2B-containing RNAs, do not show similar interactions with Kit in vivo. We conclude that the recessive Mitf mi-bws is a complex allele that can display a semi-dominant effect when present in a Kit-sensitized background. We suggest that human disease variability may equally be due to complex, allele-specific interactions between different genes.
C1 [Wen, Bin; Chen, Yu; Li, Huirong; Wang, Jing; Shen, Jie; Ma, Aobo; Hou, Ling] Sch Ophthalmol & Optometry, Dev Cell Biol & Dis Program, Wenzhou, Zhejiang, Peoples R China.
[Wen, Bin; Chen, Yu; Li, Huirong; Wang, Jing; Shen, Jie; Ma, Aobo; Hou, Ling] Zhejiang Eye Hosp, Wenzhou, Zhejiang, Peoples R China.
[Wen, Bin; Chen, Yu; Qu, Jia; Hou, Ling] Minist Hlth China, Wenzhou Med Coll, Key Lab Vis Sci, Wenzhou, Zhejiang, Peoples R China.
[Wen, Bin; Chen, Yu; Qu, Jia; Hou, Ling] Minist Hlth China, Wenzhou Med Coll, State Key Lab Cultivat Base, Wenzhou, Zhejiang, Peoples R China.
[Bismuth, Keren; Debbache, Julien; Arnheiter, Heinz] NINDS, Mammalian Dev Sect, NIH, Bethesda, MD 20892 USA.
RP Hou, L (reprint author), Sch Ophthalmol & Optometry, Dev Cell Biol & Dis Program, Wenzhou, Zhejiang, Peoples R China.
EM lhou88@gmail.com
OI Hou, Ling/0000-0003-0705-8099
FU National Basic Research Program (973 Program) of China [2009CB526502];
National Natural Science Foundation of China [30771149]; Research
Development Grant of Wenzhou Medical College; NINDS, NIH
FX We would like to thank Dr. Jean-Jacques Panthier for providing
Kittm1Alf mice and Dr. Myung K. Shin for providing
Ednrbtm1Myks mice. All animals were handled according to the
regulations of the Institutional Animal Care and Use Committee. This
research was supported in part by the National Basic Research Program
(973 Program) of China (2009CB526502), the National Natural Science
Foundation of China (30771149), the Research Development Grant of
Wenzhou Medical College (to L. H.), and the Intramural Research Program
of NINDS, NIH.
NR 36
TC 8
Z9 8
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 JUN
PY 2010
VL 23
IS 3
BP 441
EP 447
DI 10.1111/j.1755-148X.2010.00699.x
PG 7
WC Oncology; Cell Biology; Dermatology
SC Oncology; Cell Biology; Dermatology
GA 595QL
UT WOS:000277627200016
PM 20374522
ER
PT J
AU Sahut-Barnola, I
de Joussineau, C
Val, P
Lambert-Langlais, S
Damon, C
Martinez, AML
Pointud, JC
Marceau, G
Sapin, V
Tissier, F
Ragazzon, B
Bertherat, J
Kirschner, LS
Stratakis, CA
Martinez, A
AF Sahut-Barnola, Isabelle
de Joussineau, Cyrille
Val, Pierre
Lambert-Langlais, Sarah
Damon, Christelle
Martinez, Anne-Marie Lefrancois
Pointud, Jean-Christophe
Marceau, Geoffroy
Sapin, Vincent
Tissier, Frederique
Ragazzon, Bruno
Bertherat, Jerome
Kirschner, Lawrence S.
Stratakis, Constantine A.
Martinez, Antoine
TI Cushing's Syndrome and Fetal Features Resurgence in Adrenal
Cortex-Specific Prkar1a Knockout Mice
SO PLOS GENETICS
LA English
DT Article
ID NODULAR ADRENOCORTICAL-DISEASE; DEPENDENT PROTEIN-KINASE; STEROIDOGENIC
FACTOR-I; SUBUNIT TYPE 1A; CARNEY COMPLEX; REGULATORY SUBUNIT; X-ZONE;
GLUCOCORTICOID-RECEPTOR; CELL-PROLIFERATION; CORTISOL SECRETION
AB Carney complex (CNC) is an inherited neoplasia syndrome with endocrine overactivity. Its most frequent endocrine manifestation is primary pigmented nodular adrenocortical disease (PPNAD), a bilateral adrenocortical hyperplasia causing pituitary-independent Cushing's syndrome. Inactivating mutations in PRKAR1A, a gene encoding the type 1 alpha-regulatory subunit (R1 alpha) of the cAMP-dependent protein kinase (PKA) have been found in 80% of CNC patients with Cushing's syndrome. To demonstrate the implication of R1 alpha loss in the initiation and development of PPNAD, we generated mice lacking Prkar1 alpha specifically in the adrenal cortex (AdKO). AdKO mice develop pituitary-independent Cushing's syndrome with increased PKA activity. This leads to autonomous steroidogenic genes expression and deregulated adreno-cortical cells differentiation, increased proliferation and resistance to apoptosis. Unexpectedly, R1 alpha loss results in improper maintenance and centrifugal expansion of cortisol-producing fetal adrenocortical cells with concomitant regression of adult cortex. Our data provide the first in vivo evidence that loss of R1 alpha is sufficient to induce autonomous adrenal hyper-activity and bilateral hyperplasia, both observed in human PPNAD. Furthermore, this model demonstrates that deregulated PKA activity favors the emergence of a new cell population potentially arising from the fetal adrenal, giving new insight into the mechanisms leading to PPNAD.
C1 [Sahut-Barnola, Isabelle; de Joussineau, Cyrille; Val, Pierre; Lambert-Langlais, Sarah; Damon, Christelle; Martinez, Anne-Marie Lefrancois; Pointud, Jean-Christophe; Marceau, Geoffroy; Sapin, Vincent; Martinez, Antoine] Clermont Univ, CNRS, UMR6247, Aubiere, France.
[Marceau, Geoffroy] CHU G Montpied, Ctr Biol, Biochim Lab, Clermont Ferrand, France.
[Tissier, Frederique; Ragazzon, Bruno; Bertherat, Jerome] Univ Paris 05, AP HP Hop Cochin, INSERM,CNRS, Inst Cochin,Dept Endocrinol Metab & Canc,UMR8104, Paris, France.
[Kirschner, Lawrence S.] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA.
[Kirschner, Lawrence S.] Ohio State Univ, Dept Internal Med, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA.
[Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA.
RP Sahut-Barnola, I (reprint author), Clermont Univ, CNRS, UMR6247, Aubiere, France.
EM Antoine.martinez@univ-bpclermont.fr
RI Ragazzon, Bruno/E-6541-2017
OI Ragazzon, Bruno/0000-0001-9476-4973
FU Centre National de la Recherche Scientifique (CNRS); Universite Blaise
Pascal; Universite d'Auvergne; Agence Nationale pour la Recherche
[ANR06-MRAR-007, ANR08-GENOPAT-002]; Association pour la Recherche
contre le Cancer [ARC 3815]; La Ligue contre le Cancer; Region
Auvergne/Canceropole Lyon Auvergne Rhone-Alpes (CLARA)
FX This work was supported by grants from the Centre National de la
Recherche Scientifique (CNRS), Universite Blaise Pascal, Universite
d'Auvergne, Agence Nationale pour la Recherche (ANR06-MRAR-007 and
ANR08-GENOPAT-002), Association pour la Recherche contre le Cancer (ARC
3815), La Ligue contre le Cancer, Region Auvergne/Canceropole Lyon
Auvergne Rhone-Alpes (CLARA). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 61
TC 36
Z9 36
U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD JUN
PY 2010
VL 6
IS 6
AR e1000980
DI 10.1371/journal.pgen.1000980
PG 16
WC Genetics & Heredity
SC Genetics & Heredity
GA 624GN
UT WOS:000279805200010
PM 20548949
ER
PT J
AU Rodger, MA
Betancourt, MT
Clark, P
Lindqvist, PG
Dizon-Townson, D
Said, J
Seligsohn, U
Carrier, M
Salomon, O
Greer, IA
AF Rodger, Marc A.
Betancourt, Marisol T.
Clark, Peter
Lindqvist, Pelle G.
Dizon-Townson, Donna
Said, Joanne
Seligsohn, Uri
Carrier, Marc
Salomon, Ophira
Greer, Ian A.
TI The Association of Factor V Leiden and Prothrombin Gene Mutation and
Placenta-Mediated Pregnancy Complications: A Systematic Review and
Meta-analysis of Prospective Cohort Studies
SO PLOS MEDICINE
LA English
DT Review
ID INTRAUTERINE GROWTH RESTRICTION; INHERITED THROMBOPHILIA; VENOUS
THROMBOEMBOLISM; 3-UNTRANSLATED REGION; NULLIPAROUS WOMEN; RISK-FACTOR;
THROMBOSIS; OUTCOMES; POLYMORPHISMS; PREECLAMPSIA
AB Background: Factor V Leiden (FVL) and prothrombin gene mutation (PGM) are common inherited thrombophilias. Retrospective studies variably suggest a link between maternal FVL/PGM and placenta-mediated pregnancy complications including pregnancy loss, small for gestational age, pre-eclampsia and placental abruption. Prospective cohort studies provide a superior methodologic design but require larger sample sizes to detect important effects. We undertook a systematic review and a meta-analysis of prospective cohort studies to estimate the association of maternal FVL or PGM carrier status and placenta-mediated pregnancy complications.
Methods and Findings: A comprehensive search strategy was run in Medline and Embase. Inclusion criteria were: (1) prospective cohort design; (2) clearly defined outcomes including one of the following: pregnancy loss, small for gestational age, pre-eclampsia or placental abruption; (3) maternal FVL or PGM carrier status; (4) sufficient data for calculation of odds ratios (ORs). We identified 322 titles, reviewed 30 articles for inclusion and exclusion criteria, and included ten studies in the meta-analysis. The odds of pregnancy loss in women with FVL (absolute risk 4.2%) was 52% higher (OR = 1.52, 95% confidence interval [CI] 1.06-2.19) as compared with women without FVL (absolute risk 3.2%). There was no significant association between FVL and pre-eclampsia (OR = 1.23, 95% CI 0.89-1.70) or between FVL and SGA (OR = 1.0, 95% CI 0.80-1.25). PGM was not associated with pre-eclampsia (OR = 1.25, 95% CI 0.79-1.99) or SGA (OR 1.25, 95% CI 0.92-1.70).
Conclusions: Women with FVL appear to be at a small absolute increased risk of late pregnancy loss. Women with FVL and PGM appear not to be at increased risk of pre-eclampsia or birth of SGA infants.
C1 [Rodger, Marc A.; Betancourt, Marisol T.; Carrier, Marc] Univ Ottawa, Dept Med, Thrombosis Program, Div Hematol, Ottawa, ON, Canada.
[Rodger, Marc A.; Betancourt, Marisol T.; Carrier, Marc] Univ Ottawa, Dept Obstet & Gynecol, Thrombosis Program, Div Hematol, Ottawa, ON, Canada.
[Rodger, Marc A.; Betancourt, Marisol T.; Carrier, Marc] Univ Ottawa, Dept Epidemiol Community Med, Thrombosis Program, Div Hematol, Ottawa, ON, Canada.
[Rodger, Marc A.; Betancourt, Marisol T.; Carrier, Marc] Ottawa Hosp, Clin Epidemiol Program, Ottawa Hosp Res Inst, Ottawa, ON, Canada.
[Clark, Peter] Hosp & Med Sch, Dept Transfus Med, Dundee, Scotland.
[Lindqvist, Pelle G.] Karolinska Hosp, Dept Obstet & Gynecol, Huddinge, Sweden.
[Dizon-Townson, Donna] NICHHD, Maternal Fetal Med Units Network, Bethesda, MD 20892 USA.
[Said, Joanne] Royal Womens Hosp, Dept Perinatal Med, Carlton, Vic, Australia.
[Said, Joanne] Univ Melbourne, Dept Obstet & Gynaecol, Parkville, Vic 3052, Australia.
[Seligsohn, Uri; Salomon, Ophira] Chaim Sheba Med Ctr, Amalia Biron Thrombosis & Hemostasis Res Inst, IL-52621 Tel Hashomer, Israel.
[Greer, Ian A.] Hull York Med Sch, York, N Yorkshire, England.
RP Rodger, MA (reprint author), Univ Ottawa, Dept Med, Thrombosis Program, Div Hematol, Ottawa, ON, Canada.
EM mrodger@ohri.ca
RI Lindqvist, Pelle/N-9205-2013;
OI Lindqvist, Pelle/0000-0002-1652-8235; Said, Joanne/0000-0001-6263-0030
FU Heart and Stroke Foundation of Ontario; Ministry of Research and
Innovation's Early Researcher Award
FX MAR is a Career Scientist of the Heart and Stroke Foundation of Ontario
and also received Visiting Scientist funding from the Heart and Stroke
Foundation of Ontario to develop the project while visiting at The Hull
York Medical School with IAG. MAR was also supported by the Ministry of
Research and Innovation's Early Researcher Award. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 49
TC 81
Z9 88
U1 0
U2 6
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 JUN
PY 2010
VL 7
IS 6
AR e1000292
DI 10.1371/journal.pmed.1000292
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA 619AV
UT WOS:000279400000010
PM 20563311
ER
PT J
AU Van Kerkhove, MD
Asikainen, T
Becker, NG
Bjorge, S
Desenclos, JC
dos Santos, T
Fraser, C
Leung, GM
Lipsitch, M
Longini, IM
McBryde, ES
Roth, CE
Shay, DK
Smith, DJ
Wallinga, J
White, PJ
Ferguson, NM
Riley, S
AF Van Kerkhove, Maria D.
Asikainen, Tommi
Becker, Niels G.
Bjorge, Steven
Desenclos, Jean-Claude
dos Santos, Thais
Fraser, Christophe
Leung, Gabriel M.
Lipsitch, Marc
Longini, Ira M., Jr.
McBryde, Emma S.
Roth, Cathy E.
Shay, David K.
Smith, Derek J.
Wallinga, Jacco
White, Peter J.
Ferguson, Neil M.
Riley, Steven
CA WHO Informal Network Math Modellin
TI Studies Needed to Address Public Health Challenges of the 2009 H1N1
Influenza Pandemic: Insights from Modeling
SO PLOS MEDICINE
LA English
DT Editorial Material
ID INFECTIOUS-DISEASES; UNITED-STATES; VIRUS; HUMANS; TRANSMISSION;
HOUSEHOLD
C1 [Van Kerkhove, Maria D.; Fraser, Christophe; White, Peter J.; Ferguson, Neil M.] Univ London Imperial Coll Sci Technol & Med, MRC Ctr Outbreak Anal & Modelling, London SW7 2AZ, England.
[Asikainen, Tommi] Australian Natl Univ, European Ctr Dis Prevent & Control, Canberra, ACT, Australia.
[Becker, Niels G.] Australian Natl Univ, Natl Ctr Epidemiol & Populat Hlth, Canberra, ACT, Australia.
[Bjorge, Steven; dos Santos, Thais; Roth, Cathy E.] World Hlth Org, St Maurice, France.
[Desenclos, Jean-Claude] Inst Veille Sanit, St Maurice, France.
[Leung, Gabriel M.] Govt Hong Kong SAR, Food & Hlth Bur, Hong Kong, Hong Kong, Peoples R China.
[Lipsitch, Marc] Harvard Univ, Sch Publ Hlth, Ctr Communicable Dis Dynam, Boston, MA 02115 USA.
[Lipsitch, Marc] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Longini, Ira M., Jr.] Hutchinson Res Ctr, CSQUID, Vaccine & Infect Dis Inst, Seattle, WA USA.
[Longini, Ira M., Jr.] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA.
[McBryde, Emma S.] Royal Melbourne Hosp, Victorian Infect Dis Serv, Melbourne, Vic, Australia.
[Shay, David K.] US Ctr Dis Control & Prevent, Influenza Div, Atlanta, GA USA.
[Smith, Derek J.] Univ Cambridge, Dept Zool, Cambridge, England.
[Smith, Derek J.] Erasmus MC, Dept Virol, Rotterdam, Netherlands.
[Smith, Derek J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Wallinga, Jacco] Natl Inst Publ Hlth & Environm, RIVM, Ctr Infect Dis Control, NL-3720 BA Bilthoven, Netherlands.
[Wallinga, Jacco] Univ Med Ctr Utrecht, Div Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
[White, Peter J.] Hlth Protect Agcy Ctr Infect, Modelling & Econ Unit, London, England.
[Riley, Steven] Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China.
[Riley, Steven] Univ Hong Kong, Dept Community Med, Hong Kong, Hong Kong, Peoples R China.
RP Van Kerkhove, MD (reprint author), Univ London Imperial Coll Sci Technol & Med, MRC Ctr Outbreak Anal & Modelling, London SW7 2AZ, England.
EM m.vankerkhove@imperial.ac.uk
RI Ferguson, Neil/B-8578-2008; Fraser, Christophe/A-8109-2008;
OI Ferguson, Neil/0000-0002-1154-8093; Fraser,
Christophe/0000-0003-2399-9657; Shay, David/0000-0001-9619-4820; Leung,
Gabriel/0000-0002-2503-6283; Wallinga, Jacco/0000-0003-1725-5627;
McBryde, Emma/0000-0002-9570-9172; Lipsitch, Marc/0000-0003-1504-9213
FU FIC NIH HHS [3R01TW008246-01S1, R01 TW008246, R01 TW008246-01, R01
TW008246-01S1, R01 TW008246-02, R01 TW008246-03]; NIGMS NIH HHS
[1U54GM088588, U54 GM088558]; NIH HHS [DP1 OD000490, DP1-OD000490-01];
Wellcome Trust
NR 27
TC 43
Z9 43
U1 1
U2 11
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 JUN
PY 2010
VL 7
IS 6
AR e1000275
DI 10.1371/journal.pmed.1000275
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 619AV
UT WOS:000279400000008
PM 20532237
ER
PT J
AU Aravindhan, V
Mohan, V
Surendar, J
Rao, MM
Pavankumar, N
Deepa, M
Rajagopalan, R
Kumaraswami, V
Nutman, TB
Babu, S
AF Aravindhan, Vivekanandhan
Mohan, Viswanathan
Surendar, Jayagopi
Rao, Maradana Muralidhara
Pavankumar, Nathella
Deepa, Mohan
Rajagopalan, Ramanujam
Kumaraswami, Vasanthapuram
Nutman, Thomas B.
Babu, Subash
TI Decreased Prevalence of Lymphatic Filariasis among Diabetic Subjects
Associated with a Diminished Pro-Inflammatory Cytokine Response (CURES
83)
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID URBAN-RURAL EPIDEMIOLOGY; BANCROFTIAN FILARIASIS; SERUM-LEVELS; T-CELLS;
INFECTION; MELLITUS; IMMUNITY; INDIA; POPULATION; TYPE-1
AB Epidemiological studies have shown an inverse correlation between the incidence of lymphatic filariasis (LF) and the incidence of allergies and autoimmunity. However, the interrelationship between LF and type-2 diabetes is not known and hence, a cross sectional study to assess the baseline prevalence and the correlates of sero-positivity of LF among diabetic subjects was carried out (n = 1416) as part of the CURES study. There was a significant decrease in the prevalence of LF among diabetic subjects (both newly diagnosed [5.7%] and those under treatment [4.3%]) compared to pre-diabetic subjects [9.1%] (p = 0.0095) and non-diabetic subjects [10.4%] (p = 0.0463). A significant decrease in filarial antigen load (p = 0.04) was also seen among diabetic subjects. Serum cytokine levels of the pro-inflammatory cytokines-IL-6 and GM-CSF-were significantly lower in diabetic subjects who were LF positive, compared to those who were LF negative. There were, however, no significant differences in the levels of anti-inflammatory cytokines-IL-10, IL-13 and TGF-beta-between the two groups. Although a direct causal link has yet to be shown, there appears to be a striking inverse relationship between the prevalence of LF and diabetes, which is reflected by a diminished pro-inflammatory cytokine response in Asian Indians with diabetes and concomitant LF.
C1 [Aravindhan, Vivekanandhan; Mohan, Viswanathan; Surendar, Jayagopi; Rao, Maradana Muralidhara; Deepa, Mohan; Rajagopalan, Ramanujam] Madras Diabet Res Fdn, Madras, Tamil Nadu, India.
[Mohan, Viswanathan] Dr Mohans Diabet Specialties Ctr, Madras, Tamil Nadu, India.
[Pavankumar, Nathella; Babu, Subash] Int Ctr Excellence Res, Natl Inst Hlth, Madras, Tamil Nadu, India.
[Kumaraswami, Vasanthapuram] TB Res Ctr, Madras, Tamil Nadu, India.
[Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Babu, Subash] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA.
RP Aravindhan, V (reprint author), Madras Diabet Res Fdn, Madras, Tamil Nadu, India.
EM cvaravindhan@yahoo.co.uk
OI Aravindhan, Vivekanandhan/0000-0002-5639-4948
FU Chennai Willingdon Corporate Foundation; TRC-NIH-ICER
FX The CURES field studies were supported by the Chennai Willingdon
Corporate Foundation. In addition, funding was also provided through the
TRC-NIH-ICER. No potential conflicts of interest relevant to this
article were reported. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 30
TC 18
Z9 18
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD JUN
PY 2010
VL 4
IS 6
AR e707
DI 10.1371/journal.pntd.0000707
PG 6
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 618HD
UT WOS:000279341300016
PM 20559443
ER
PT J
AU de Moura, TR
Oliveira, F
Rodrigues, GC
Carneiro, MW
Fukutani, KF
Novais, FO
Miranda, JC
Barral-Netto, M
Brodskyn, C
Barral, A
de Oliveira, CI
AF de Moura, Tatiana R.
Oliveira, Fabiano
Rodrigues, Gabriele C.
Carneiro, Marcia W.
Fukutani, Kiyoshi F.
Novais, Fernanda O.
Miranda, Jose Carlos
Barral-Netto, Manoel
Brodskyn, Claudia
Barral, Aldina
de Oliveira, Camila I.
TI Immunity to Lutzomyia intermedia Saliva Modulates the Inflammatory
Environment Induced by Leishmania braziliensis
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID SAND FLY SALIVA; CUTANEOUS LEISHMANIASIS; NEUTROPHIL MIGRATION; MAJOR
INFECTION; HUMAN MONOCYTES; VECTOR SALIVA; NATURAL MODEL; BALB/C MICE;
MOUSE MODEL; IN-VITRO
AB Background: During blood feeding, sand flies inject Leishmania parasites in the presence of saliva. The types and functions of cells present at the first host-parasite contact are critical to the outcome on infection and sand fly saliva has been shown to play an important role in this setting. Herein, we investigated the in vivo chemotactic effects of Lutzomyia intermedia saliva, the vector of Leishmania braziliensis, combined or not with the parasite.
Methods and Findings: We tested the initial response induced by Lutzomyia intermedia salivary gland sonicate (SGS) in BALB/c mice employing the air pouch model of inflammation. L. intermedia SGS induced a rapid influx of macrophages and neutrophils. In mice that were pre-sensitized with L. intermedia saliva, injection of SGS was associated with increased neutrophil recruitment and a significant up-regulation of CXCL1, CCL2, CCL4 and TNF-alpha expression. Surprisingly, in mice that were pre-exposed to SGS, a combination of SGS and L. braziliensis induced a significant migration of neutrophils and an important modulation in cytokine and chemokine expression as shown by decreased CXCL10 expression and increased IL-10 expression.
Conclusion: These results confirm that sand fly saliva modulates the initial host response. More importantly, pre-exposure to L. intermedia saliva significantly modifies the host's response to L. braziliensis, in terms of cellular recruitment and expression of cytokines and chemokines. This particular immune modulation may, in turn, favor parasite multiplication.
C1 [de Moura, Tatiana R.; Rodrigues, Gabriele C.; Carneiro, Marcia W.; Fukutani, Kiyoshi F.; Novais, Fernanda O.; Miranda, Jose Carlos; Barral-Netto, Manoel; Brodskyn, Claudia; Barral, Aldina; de Oliveira, Camila I.] Fundacao Oswaldo Cruz FIOCRUZ, Ctr Pesquisas Goncalo Moniz, Salvador, BA, Brazil.
[Oliveira, Fabiano] NIAID, Vector Mol Biol Unit, NIH, Bethesda, MD 20892 USA.
[Barral-Netto, Manoel; Brodskyn, Claudia; Barral, Aldina] Univ Fed Bahia, Salvador, BA, Brazil.
[Barral-Netto, Manoel; Brodskyn, Claudia; Barral, Aldina; de Oliveira, Camila I.] Inst Nacl Ciencia & Tecnol Invest Imunol, Sao Paulo, Brazil.
RP de Moura, TR (reprint author), Univ Fed Sergipe, Ctr Ciencias Biol & Saude, Aracaju, Brazil.
EM camila@bahia.fiocruz.br
RI Oliveira, Fabiano/B-4251-2009; Barral Netto, Manoel/B-3904-2009; de
Oliveira, Camila/B-4358-2009; Barral, Aldina/B-4191-2009; Imunologia,
Inct/I-2124-2013; DE MOURA, TATIANA/L-4556-2016; Fukutani,
Kiyoshi/N-7905-2016
OI Oliveira, Fabiano/0000-0002-7924-8038; Barral Netto,
Manoel/0000-0002-5823-7903; de Oliveira, Camila/0000-0002-7868-5164;
Barral, Aldina/0000-0002-7177-464X; DE MOURA,
TATIANA/0000-0002-7442-4434; Fukutani, Kiyoshi/0000-0003-2223-0918
FU FAPESB; PAPES/FIOCRUZ; CNPq
FX This work was supported by grants from FAPESB, PAPES/FIOCRUZ, and CNPq.
TRdM was supported by a CNPq fellowship. MB-N, CB, AB, and CIdO are
senior investigators from CNPq. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 53
TC 23
Z9 23
U1 0
U2 3
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 JUN
PY 2010
VL 4
IS 6
AR e712
DI 10.1371/journal.pntd.0000712
PG 9
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 618HD
UT WOS:000279341300020
PM 20559550
ER
PT J
AU Berger, EA
Pastan, I
AF Berger, Edward A.
Pastan, Ira
TI Immunotoxin Complementation of HAART to Deplete Persisting HIV-Infected
Cell Reservoirs
SO PLOS PATHOGENS
LA English
DT Editorial Material
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; EXOTOXIN
HYBRID PROTEIN; CD4(+) T-CELLS; REVERSE-TRANSCRIPTASE INHIBITORS;
CD4-PSEUDOMONAS EXOTOXIN; IN-VITRO; ENVELOPE GLYCOPROTEINS; PSEUDOMONAS
EXOTOXIN; FUTURE-DIRECTIONS
C1 [Berger, Edward A.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
[Pastan, Ira] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Berger, EA (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
EM edward_berger@nih.gov
FU Intramural NIH HHS [ZIA AI000538-24]
NR 68
TC 23
Z9 23
U1 1
U2 4
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 JUN
PY 2010
VL 6
IS 6
AR e1000803
DI 10.1371/journal.ppat.1000803
PG 6
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 624GX
UT WOS:000279806300001
PM 20548940
ER
PT J
AU Fant, M
Farina, A
Nagaraja, R
Schlessinger, D
AF Fant, Michael
Farina, Antonio
Nagaraja, Ramaiah
Schlessinger, David
TI PLAC1 (Placenta-specific 1): a novel, X-linked gene with roles in
reproductive and cancer biology
SO PRENATAL DIAGNOSIS
LA English
DT Review
DE Placenta-specific 1; placenta; cancer
ID MESSENGER-RNA; MATERNAL PLASMA; ES CELLS; MOUSE; PREECLAMPSIA; PROTEIN;
DOMAIN; CHROMOSOME; EXPRESSION; CLEARANCE
AB Placenta-specific 1 (PLACI) is a recently described X-linked gene with expression restricted primarily to cells derived from trophoblast lineage during embryonic development. PLACI localizes to a region of the X chromosome thought to be important in placental development although its role in this process has not been defined. This review summarizes our current understanding of its expression, regulation, and function. PLACI is expressed throughout human pregnancy by the differentiated trophoblast and localizes to membranous structures in the syncytiotrophoblast, including the microvillous plasma membrane surface. Recent studies have demonstrated that PLACI is also expressed by a wide variety of human cancers. Studies of the PLACI promoter regions indicate that its expression in both normal placenta and cancer cells is driven by specific interactions involving a combination of transcription factors. Although functional insight into PLAC I in the normal trophoblast is lacking, preliminary studies suggest that cancer-derived PLAC I has the potential to promote tumor growth and function. In addition, it also appears to elicit a specific immunologic response that may influence survival in some cancer patients, suggesting that it may provide a therapeutic target for the treatment of some cancers. We also discuss a potential role for PLAC I as a biomarker predictive of specific pregnancy complications, such as preecktmpsia. Copyright (C) 2010 John Wiley & Sons, Ltd.
C1 [Fant, Michael] Univ S Florida, Coll Med, Dept Pediat, Tampa, FL 33606 USA.
[Farina, Antonio] Univ Bologna, Dept Histol & Human Embryol, Bologna, Italy.
[Nagaraja, Ramaiah; Schlessinger, David] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA.
RP Fant, M (reprint author), Univ S Florida, Coll Med, Dept Pediat, 2 Tampa Gen Circle,5th Floor, Tampa, FL 33606 USA.
EM mfant@health.usf.edu
OI Farina, Antonio/0000-0002-6862-1810
FU National Institute on Aging, NIH; NIH [HD41404, 048862]
FX The research presented in this review was supported, in part, by the
Intramural Research Program of the National Institute on Aging, NIH (R.
N, D. S) and NIH grants HD41404 and 048862 (M. E. F.).
NR 35
TC 12
Z9 12
U1 0
U2 0
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0197-3851
J9 PRENATAL DIAG
JI Prenat. Diagn.
PD JUN
PY 2010
VL 30
IS 6
BP 497
EP 502
DI 10.1002/pd.2506
PG 6
WC Genetics & Heredity; Obstetrics & Gynecology
SC Genetics & Heredity; Obstetrics & Gynecology
GA 614OU
UT WOS:000279070400001
PM 20509147
ER
PT J
AU Caleshu, C
Shiloh, S
Price, C
Sapp, J
Biesecker, B
AF Caleshu, Colleen
Shiloh, Shoshana
Price, Cristofer
Sapp, Julie
Biesecker, Barbara
TI Invasive prenatal testing decisions in pregnancy after infertility
SO PRENATAL DIAGNOSIS
LA English
DT Article
DE prenatal testing; infertility; decisional conflict; decision making;
genetic counseling
ID INTRACYTOPLASMIC SPERM INJECTION; IN-VITRO FERTILIZATION; ADVANCED
MATERNAL AGE; ASSISTED REPRODUCTION; INVITRO FERTILIZATION; EMOTIONAL
RESPONSES; IVF COUPLES; DIAGNOSIS; WOMEN; AMNIOCENTESIS
AB Objective This study assessed decisional conflict about invasive prenatal testing among women pregnant after infertility.
Methods We surveyed 180 pregnant women with a history of infertility using a mixed methods cross-sectional design. Difficulty in deciding whether to have prenatal testing was measured using the Decisional Conflict Scale.
Results A minority of women (31%) chose to have invasive prenatal testing. Most participants (72%) reported low decisional conflict (score <25; mean = 22.1; standard deviation = 23.2; range: 0-100). Half (53%) of the participants said that infertility made the testing decision easier. Qualitative data suggest that infertility makes the decision easier by clarifying relevant values and priorities. Most infertility characteristics studied were not significantly associated with decisional conflict. Variables associated with higher decisional conflict included infertility distress due to rejection of a childfree lifestyle, disagreement with others about testing, and choosing to have invasive testing after having had treatment for infertility.
Conclusions For some women, infertility may make the invasive prenatal testing decision easier. Women with the greatest need for decisional support were those who have had treatment and choose invasive testing, who disagree with others about their testing choice, or who are particularly distressed about being childless. Copyright (C) 2010 John Wiley & Sons, Ltd.
C1 [Caleshu, Colleen] Univ Calif San Francisco, Div Med Genet, San Francisco, CA 94143 USA.
[Shiloh, Shoshana] Tel Aviv Univ, Dept Psychol, IL-69978 Tel Aviv, Israel.
[Price, Cristofer] ABT Associates Inc, Bethesda, MD USA.
[Sapp, Julie] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Biesecker, Barbara] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
RP Caleshu, C (reprint author), Univ Calif San Francisco, Div Med Genet, Box 0794, San Francisco, CA 94143 USA.
EM colleen.brown@ucsf.edu
FU National Institutes of Health
FX The authors thank Rajiv Rimal, PhD, for his input into the early study
design process. This research was funded by the National Human Genome
Research Institute intramural research program, National Institutes of
Health.
NR 43
TC 3
Z9 3
U1 1
U2 6
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0197-3851
J9 PRENATAL DIAG
JI Prenat. Diagn.
PD JUN
PY 2010
VL 30
IS 6
BP 575
EP 581
DI 10.1002/pd.2529
PG 7
WC Genetics & Heredity; Obstetrics & Gynecology
SC Genetics & Heredity; Obstetrics & Gynecology
GA 614OU
UT WOS:000279070400014
PM 20509160
ER
PT J
AU Chiang, YJ
Calado, RT
Hathcock, KS
Lansdorp, PM
Young, NS
Hodes, RJ
AF Chiang, Y. Jeffrey
Calado, Rodrigo T.
Hathcock, Karen S.
Lansdorp, Peter M.
Young, Neal S.
Hodes, Richard J.
TI Telomere length is inherited with resetting of the telomere set-point
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE dyskeratosis congenita; haploinsufficiency; telomerase; aplastic anemia;
pulmonary fibrosis
ID REVERSE-TRANSCRIPTASE; DYSKERATOSIS-CONGENITA; IN-VIVO; MAINTENANCE;
CELLS; HAPLOINSUFFICIENCY; CHROMOSOME; MUTATIONS; RNA; DEFECTS
AB We have studied models of telomerase haploinsufficiency in humans and mice to analyze regulation of telomere length and the significance of "set points" in inheritance of telomere length. In three families with clinical syndromes associated with short telomeres resulting from haploinsufficient mutations in TERT, the gene encoding telomerase reverse transcriptase, we asked whether restoration of normal genotypes in offspring of affected individuals would elongate inherited short telomeres. Telomeres were shorter than normal in some but not all genotypically normal offspring of telomerase-mutant parents or grandparents. Analysis of these findings was complicated by heterogeneity of telomere length among individuals, as well as by the admixing of telomeres inherited from affected parents with those inherited from unaffected ("wild-type" TERT) parents. To understand further the inheritance of telomere length, we established a shortened-telomere mouse model. When Tert(+/-) heterozygous mice were successively cross-bred through 17 generations, telomere length shortened progressively. The late-generation Tert(+/-) mice were intercrossed to produce genotypically wild-type Tert(+/+) mice, for which telomere length was characterized. Strikingly, telomere length in these Tert(+/+) mice was not longer than that of their Tert(+/-) parents. Moreover, when successive crosses were carried out among these short-telomere Tert(+/+) off-spring mice, telomere length was stable, with no elongation up to six generations. This breeding strategy therefore has established a mouse strain, B6.ST (short telomeres), with C57BL/6 genotype and stable short telomeres. These findings suggest that the set point of telomere lengths of offspring is determined by the telomere lengths of their parents in the presence of normal expression of telomerase.
C1 [Chiang, Y. Jeffrey; Hathcock, Karen S.; Hodes, Richard J.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Calado, Rodrigo T.; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Hodes, Richard J.] NIA, NIH, Bethesda, MD 20892 USA.
[Lansdorp, Peter M.] British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada.
RP Chiang, YJ (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM chiangj@mail.nih.gov
RI Calado, Rodrigo/G-2619-2011
FU National Institutes of Health, National Cancer Institute
FX We thank Genevieve Sanchez-Howard and the staff at Bioqual for expert
animal care and breeding. We thank Michael Kruhlak for helping with
Q-FISH analysis, Irma Vulto for helping measure actual telomere length,
David Winkler and Jeffrey Hammer for helping isolate mouse-tail DNAs,
and Susan Sharrow for helping in FACS analysis. We thank Nan-ping Weng
for his critical reading and helpful comments. This research was
supported by the Intramural Research Program of the National Institutes
of Health, National Cancer Institute.
NR 33
TC 43
Z9 43
U1 0
U2 7
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUN 1
PY 2010
VL 107
IS 22
BP 10148
EP 10153
DI 10.1073/pnas.0913125107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 603ZD
UT WOS:000278246000045
PM 20479226
ER
PT J
AU Scholvinck, ML
Maier, A
Ye, FQ
Duyn, JH
Leopold, DA
AF Schoelvinck, Marieke L.
Maier, Alexander
Ye, Frank Q.
Duyn, Jeff H.
Leopold, David A.
TI Neural basis of global resting-state fMRI activity
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE cortex; electrophysiology; local field potential; functional
connectivity; monkey
ID DEFAULT-MODE NETWORK; FUNCTIONAL CONNECTIVITY; VISUAL-CORTEX;
NEURONAL-ACTIVITY; ONGOING ACTIVITY; BRAIN ACTIVITY; MOTOR CORTEX;
FLUCTUATIONS; DYNAMICS; STIMULUS
AB Functional MRI (fMRI) has uncovered widespread hemodynamic. uctuations in the brain during rest. Recent electroencephalographic work in humans and microelectrode recordings in anesthetized monkeys have shown this activity to be correlated with slow changes in neural activity. Here we report that the spontaneous. uctuations in the local. eld potential (LFP) measured from a single cortical site in monkeys at rest exhibit widespread, positive correlations with fMRI signals over nearly the entire cerebral cortex. This correlation was especially consistent in a band of upper gamma- range frequencies (40-80 Hz), for which the hemodynamic signal lagged the neural signal by 6-8 s. A strong, positive correlation was also observed in a band of lower frequencies (2-15 Hz), albeit with a lag closer to zero. The global pattern of correlation with spontaneous fMRI. uctuations was similar whether the LFP signal was measured in occipital, parietal, or frontal electrodes. This coupling was, however, dependent on the monkey's behavioral state, being stronger and anticipatory when the animals' eyes were closed. These results indicate that the often discarded global component of fMRI. uctuations measured during the resting state is tightly coupled with underlying neural activity.
C1 [Schoelvinck, Marieke L.; Maier, Alexander; Leopold, David A.] NIMH, Unit Cognit Neurophysiol & Imaging, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
[Schoelvinck, Marieke L.] UCL, Inst Ophthalmol, London EC1V 9EL, England.
[Ye, Frank Q.; Leopold, David A.] Natl Inst Neurol Disorders & Stroke, Neurophysiol Imaging Facil, NIMH, Bethesda, MD 20892 USA.
[Ye, Frank Q.; Leopold, David A.] NEI, NIH, Bethesda, MD 20892 USA.
[Duyn, Jeff H.] Natl Inst Neurol Disorders & Stroke, Sect Adv Imaging, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
RP Leopold, DA (reprint author), NIMH, Unit Cognit Neurophysiol & Imaging, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
EM leopoldd@mail.nih.gov
RI Duyn, Jozef/F-2483-2010; Maier, Alexander/B-7489-2009;
OI Maier, Alexander/0000-0002-7250-502X; Leopold, David/0000-0002-1345-6360
FU National Institute of Mental Health; National Institute of Neurological
Disorders and Stroke; National Eye Institute; Wellcome Trust
FX We thank C. Zhu and K. Smith for assisting with the experiments, Dr. M.
Schmid for help with the fMRI analysis, G. Dold, D. Ide, and T. Talbot
for design and machining of MR-compatible materials used for data
collection, and Drs. A. Silva, J. Walters, and A. Shmuel for discussion.
Research was supported by the Intramural Programs of the National
Institute of Mental Health, National Institute of Neurological Disorders
and Stroke, and National Eye Institute. M.L.S. was supported by the
Wellcome Trust.
NR 40
TC 281
Z9 284
U1 6
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 JUN 1
PY 2010
VL 107
IS 22
BP 10238
EP 10243
DI 10.1073/pnas.0913110107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 603ZD
UT WOS:000278246000060
PM 20439733
ER
PT J
AU Bruzzone, R
Dubois-Dalcq, M
Kristensson, K
AF Bruzzone, Roberto
Dubois-Dalcq, Monique
Kristensson, Krister
TI Neurobiology of infectious diseases: Bringing them out of neglect
Foreword
SO PROGRESS IN NEUROBIOLOGY
LA English
DT Editorial Material
ID VIRUS
C1 [Kristensson, Krister] Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden.
[Bruzzone, Roberto] HKU Pasteur Res Ctr, Hong Kong, Hong Kong, Peoples R China.
[Dubois-Dalcq, Monique] NINDS, NIH, Bethesda, MD 20892 USA.
RP Kristensson, K (reprint author), Karolinska Inst, Dept Neurosci, Retzius Vag 8,A2, S-17177 Stockholm, Sweden.
EM krister.kristensson@ki.se
RI Bruzzone, Roberto/C-4719-2009
OI Bruzzone, Roberto/0000-0003-4373-1447
NR 13
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 0301-0082
J9 PROG NEUROBIOL
JI Prog. Neurobiol.
PD JUN
PY 2010
VL 91
IS 2
SI SI
BP 91
EP 94
DI 10.1016/j.pneurobio.2009.12.005
PG 4
WC Neurosciences
SC Neurosciences & Neurology
GA 603WK
UT WOS:000278238600001
PM 20026171
ER
PT J
AU Mahanty, S
Garcia, HH
AF Mahanty, Siddhartha
Garcia, Hector H.
CA Cysticercosis Working Grp Peru
TI Cysticercosis and neurocysticercosis as pathogens affecting the nervous
system
SO PROGRESS IN NEUROBIOLOGY
LA English
DT Review
DE Cysticercosis; Neurocysticercosis; Taenia solium; Seizures;
Immunopathology; Immune regulation
ID TAENIA-SOLIUM CYSTICERCOSIS; ALTERNATIVELY ACTIVATED MACROPHAGES;
DELTA-T-CELLS; IMMUNE-RESPONSE; MURINE CYSTICERCOSIS;
CEREBROSPINAL-FLUID; TAPEWORM INFECTION; IN-VITRO; CALCIFIED
NEUROCYSTICERCOSIS; IMMUNOLOGICAL RESPONSES
AB Taenia solium cysticercosis is still a major cause of seizures around the world. Despite an extensive body of published literature on this topic, knowledge of the biology, immunology, pathophysiology, and treatment of this parasite remains largely incomplete. This review summarizes recent information on the biology, clinical manifestations, immunopathology treatment and control of this important and neglected zoonotic disease, with emphasis on areas where recent developments have changed traditional and established views. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Garcia, Hector H.] Univ Peruana Cayetano Heredia, Lima, Peru.
[Mahanty, Siddhartha] NIAID, NIH, Bethesda, MD 20892 USA.
[Garcia, Hector H.] Inst Ciencias Neurol, Lima, Peru.
RP Garcia, HH (reprint author), Univ Peruana Cayetano Heredia, Lima, Peru.
EM hgarcia@jhsph.edu
OI Mahanty, Siddhartha/0000-0003-1068-0524
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX This research was supported, in part, by the Intramural Research Program
of the National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 132
TC 34
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U1 0
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0301-0082
J9 PROG NEUROBIOL
JI Prog. Neurobiol.
PD JUN
PY 2010
VL 91
IS 2
SI SI
BP 172
EP 184
DI 10.1016/j.pneurobio.2009.12.008
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA 603WK
UT WOS:000278238600009
PM 20035822
ER
PT J
AU Schneier, FR
Foose, TE
Hasin, DS
Heimberg, RG
Liu, SM
Grant, BF
Blanco, C
AF Schneier, F. R.
Foose, T. E.
Hasin, D. S.
Heimberg, R. G.
Liu, S. -M.
Grant, B. F.
Blanco, C.
TI Social anxiety disorder and alcohol use disorder co-morbidity in the
National Epidemiologic Survey on Alcohol and Related Conditions
SO PSYCHOLOGICAL MEDICINE
LA English
DT Article
DE Alcohol dependence; alcohol abuse; anxiety disorders; epidemiology;
social phobia
ID COMORBIDITY SURVEY REPLICATION; SUBSTANCE-ABUSE TREATMENT; COMMON
MENTAL-DISORDERS; DSM-IV DISORDERS; UNITED-STATES; FAMILY-HISTORY;
GENERAL-POPULATION; DEPENDENT PATIENTS; PREVALENCE; STRESS
AB Background. To assess the prevalence and clinical impact of co-morbid social anxiety disorder (SAD) and alcohol use disorders (AUD, i.e. alcohol abuse and alcohol dependence) in a nationally representative sample of adults in the United States.
Method. Data came from a large representative sample of the US population. Face-to-face interviews of 43093 adults residing in households were conducted during 2001-2002. Diagnoses of mood, anxiety, alcohol and drug use disorders and personality disorders were based on the Alcohol Use Disorder and Associated Disabilities Interview Schedule DSM-IV version.
Results. Lifetime prevalence of co-morbid AUD and SAD in the general population was 2.4%. SAD was associated with significantly increased rates of alcohol dependence [odds ratio (OR) 2.8] and alcohol abuse (OR 1.2). Among respondents with alcohol dependence, SAD was associated with significantly more mood, anxiety, psychotic and personality disorders. Among respondents with SAD, alcohol dependence and abuse were most strongly associated with more substance use disorders, pathological gambling and antisocial personality disorders. SAD occurred before alcohol dependence in 79.7% of co-morbid cases, but co-morbidity status did not influence age of onset for either disorder. Co-morbid SAD was associated with increased severity of alcohol dependence and abuse. Respondents with co-morbid SAD and alcohol dependence or abuse reported low rates of treatment-seeking.
Conclusions. Co-morbid lifetime AUD and SAD is a prevalent dual diagnosis, associated with substantial rates of additional co-morbidity, but remaining largely untreated. Future research should clarify the etiology of this comorbid presentation to better identify effective means of intervention.
C1 [Grant, B. F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA.
[Schneier, F. R.; Foose, T. E.; Hasin, D. S.; Liu, S. -M.; Blanco, C.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Schneier, F. R.; Foose, T. E.; Hasin, D. S.; Blanco, C.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA.
[Hasin, D. S.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.
[Heimberg, R. G.] Temple Univ, Dept Psychol, Philadelphia, PA 19122 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
FU National Institute on Alcohol Abuse and Alcoholism; National Institutes
of Health (NIH) [DA019606, DA020783, DA023200, MH076051, AA08159,
AA00161]; American Foundation for Suicide Prevention; New York State
Psychiatric Institute
FX The National Epidemiologic Survey on Alcohol and Related Conditions was
sponsored by the National Institute on Alcohol Abuse and Alcoholism and
funded, in part, by the Intramural Program, NIAAA, National Institutes
of Health. This study is supported by NIH grants DA019606, DA020783,
DA023200 and MH076051 (Dr Blanco), AA08159 and AA00161 (Dr Hasin), the
American Foundation for Suicide Prevention (Dr Blanco) and the New York
State Psychiatric Institute (Drs Foose, Hasin, Schneier and Blanco). 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 the US government.
NR 59
TC 68
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U1 5
U2 26
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0033-2917
J9 PSYCHOL MED
JI Psychol. Med.
PD JUN
PY 2010
VL 40
IS 6
BP 977
EP 988
DI 10.1017/S0033291709991231
PG 12
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 603WZ
UT WOS:000278240100010
PM 20441690
ER
PT J
AU Negus, SS
Morrissey, EM
Rosenberg, M
Cheng, K
Rice, KC
AF Negus, S. Stevens
Morrissey, Ember M.
Rosenberg, Marisa
Cheng, K.
Rice, Kenner C.
TI Effects of kappa opioids in an assay of pain-depressed intracranial
self-stimulation in rats
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE U69,593; Norbinaltorphimine; Morphine; Kappa opioid agonist; Kappa
opioid antagonist; Intracranial self-stimulation; Pain; Nociception;
Analgesia; Antinociception
ID NOR-BINALTORPHIMINE; RHESUS-MONKEYS; RECEPTOR ANTAGONISTS; PRECLINICAL
ASSAYS; ANALGESIC EFFICACY; AGONISTS; MORPHINE; BEHAVIORS; POTENT;
ANTINOCICEPTION
AB Selective, centrally acting kappa opioid agonists produce antinociception in a wide range of preclinical assays, but these compounds perform poorly as analgesics in humans. This discrepancy may be related to the behavioral depressant effects of kappa agonists. Kappa antagonists do not typically produce antinociception, but they produce antidepressant-like effects in some preclinical assays.
The objective of this study was to test the hypothesis that the kappa agonist U69,593 and the kappa antagonist norbinaltorphimine would produce pronociceptive and antinociceptive effects, respectively, in an assay of pain-depressed behavior.
Effects of U69,593 (0.056-0.56 mg/kg), norbinaltorphimine (10-32 mg/kg), and morphine (3.2 mg/kg) were evaluated on the stimulation of a stretching response and the depression of intracranial self-stimulation (ICSS) of the medial forebrain bundle produced in rats by a common noxious stimulus (intraperitoneal administration of dilute lactic acid).
U69,593 produced a dose-dependent blockade of acid-stimulated stretching but only exacerbated acid-induced depression of ICSS. Thus, U69,593 produced antinociception in the assay of pain-stimulated behavior but pronociceptive effects in the assay of pain-depressed behavior. Norbinaltorphimine did not alter acid-stimulated stretching or acid-induced depression of ICSS. The mu opioid agonist morphine blocked both acid-stimulated stretching and acid-induced depression of ICSS.
These results support the hypothesis that prodepressant effects of kappa agonists may limit their clinical utility as analgesics. These results do not support the use of kappa antagonists to treat depressant effects of pain. These findings illustrate the potential value of using complementary assays of pain-stimulated and pain-depressed behaviors for preclinical evaluation of candidate analgesics.
C1 [Negus, S. Stevens; Morrissey, Ember M.; Rosenberg, Marisa] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA.
[Cheng, K.; Rice, Kenner C.] NIDA, Chem Biol Res Branch, Bethesda, MD 20892 USA.
[Cheng, K.; Rice, Kenner C.] NIAAA, NIH, DHHS, Bethesda, MD USA.
RP Negus, SS (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, 410 N 12th St, Richmond, VA 23298 USA.
EM ssnegus@vcu.edu
FU National Institute on Drug Abuse [R01-DA11460]; National Institute on
Neurological Disorders and Stroke [R01-NS070715]; National Institute on
Alcohol Abuse and Alcoholism
FX This work was supported in part by grants R01-DA11460 from the National
Institute on Drug Abuse and R01-NS070715 from the National Institute on
Neurological Disorders and Stroke. A portion of this work was also
supported by the Intramural Research Programs of the National Institute
on Drug Abuse and the National Institute on Alcohol Abuse and
Alcoholism.
NR 53
TC 35
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U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD JUN
PY 2010
VL 210
IS 2
SI SI
BP 149
EP 159
DI 10.1007/s00213-009-1770-6
PG 11
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 592XW
UT WOS:000277416300005
PM 20101391
ER
PT J
AU Tejeda, HA
Chefer, VI
Zapata, A
Shippenberg, TS
AF Tejeda, Hugo A.
Chefer, Vladimir I.
Zapata, Agustin
Shippenberg, Toni S.
TI The effects of kappa-opioid receptor ligands on prepulse inhibition and
CRF-induced prepulse inhibition deficits in the rat
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Prepulse inhibition; Kappa-opioid receptors; Corticotropin-releasing
factor; Rat
ID CORTICOTROPIN-RELEASING-FACTOR; ACOUSTIC STARTLE RESPONSE; MESSENGER-RNA
EXPRESSION; MEDIAL PREFRONTAL CORTEX; POSTTRAUMATIC-STRESS-DISORDER;
STRAIN DIFFERENCES; NUCLEUS-ACCUMBENS; SALVINORIN-A; GLUTAMATE
RECEPTORS; ANTIPSYCHOTIC-DRUGS
AB Kappa-opioid receptor (KOR) agonists produce dysphoria and psychotomimesis in humans. KORs are enriched in the prefrontal cortex and other brain regions that regulate mood and cognitive function. Dysregulation of the dynorphin/KOR system has been implicated in the pathogenesis of schizophrenia, depression, and bipolar disorder. Prepulse inhibition of the acoustic startle reflex (PPI), a sensorimotor gating process, is disrupted in many psychiatric disorders.
The present study determined whether KOR ligands alter PPI in rats.
Utilizing a range of doses of the synthetic KOR agonists (+/-) U50,488, (-) U50,488, and U69,593 and the naturally occurring KOR agonist, Salvinorin A, we demonstrate that KOR activation does not alter PPI or startle reactivity in rats. Similarly, selective KOR blockade using the long-acting antagonist nor-binaltorphimine (nor-BNI) was without effect. In contrast to KOR ligands, MK-801 and quinpirole produced deficits in PPI. Stress and corticotropin-releasing factor (CRF) decrease PPI levels. The dynorphin/KOR system has been suggested to be a key mediator of various behavioral effects produced by stress and CRF. We therefore examined the contribution of KORs to CRF-induced alterations in PPI. Intracerebroventricular infusion of CRF decreased PPI. Administration of nor-BNI failed to affect the CRF-evoked disruption in PPI.
Together, these results provide no evidence of a link between the dynorphin/KOR system and deficits in sensory gating processes. Additional studies, however, examining whether dysregulation of this opioid system contributes to cognitive deficits and other behavioral abnormalities associated with psychiatric disorders are warranted.
C1 [Tejeda, Hugo A.; Chefer, Vladimir I.; Zapata, Agustin; Shippenberg, Toni S.] NIDA, Integrat Neurosci Sect, Integrat Neurosci Branch, NIH, Baltimore, MD 21224 USA.
[Tejeda, Hugo A.] Univ Maryland, Program Neurosci, Baltimore, MD 21201 USA.
RP Shippenberg, TS (reprint author), NIDA, Integrat Neurosci Sect, Integrat Neurosci Branch, NIH, NIDA IRP 333 Cassell Dr, Baltimore, MD 21224 USA.
EM tshippen@intra.nida.nih.gov
FU NIH; Ford Foundation
FX This research was supported by the NIDA Intramural Research Program of
NIH and a Ford Foundation Predoctoral Fellowship. We thank Dr. Thomas
Prinzano, Department of Medicinal Chemistry, The University of Kansas,
Lawrence, KS, USA, for generously providing Salvinorin A for these
studies. The authors would like to thank Sean Mansoory and Vicky Minny
for their excellent technical assistance.
NR 81
TC 15
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U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD JUN
PY 2010
VL 210
IS 2
SI SI
BP 231
EP 240
DI 10.1007/s00213-010-1799-6
PG 10
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 592XW
UT WOS:000277416300013
PM 20232058
ER
PT J
AU Nemeth, CL
Paine, TA
Rittiner, JE
Beguin, C
Carroll, FI
Roth, BL
Cohen, BM
Carlezon, WA
AF Nemeth, Christina L.
Paine, Tracie A.
Rittiner, Joseph E.
Beguin, Cecile
Carroll, F. Ivy
Roth, Bryan L.
Cohen, Bruce M.
Carlezon, William A., Jr.
TI Role of kappa-opioid receptors in the effects of salvinorin A and
ketamine on attention in rats
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Kappa agonist; NMDA antagonist; Attention; Motivation; Behavior; Model;
Rat
ID BRAIN-STIMULATION REWARD; REACTION-TIME-TASK; SALVIA-DIVINORUM;
NUCLEUS-ACCUMBENS; AGONIST; COCAINE; SCHIZOPHRENIA; DOPAMINE;
ANTAGONIST; PHENCYCLIDINE
AB Disruptions in perception and cognition are characteristic of psychiatric conditions such as schizophrenia. Studies of pharmacological agents that alter perception and cognition in humans might provide a better understanding of the brain substrates of these complex processes. One way to study these states in rodents is with tests that require attention and visual perception for correct performance.
We examined the effects of two drugs that cause disruptions in perception and cognition in humans-the kappa-opioid receptor (KOR) agonist salvinorin A (salvA; 0.125-4.0 mg/kg) and the non-competitive NMDA receptor antagonist ketamine (0.63-20 mg/kg)-on behavior in rats using the 5-choice serial reaction time task (5CSRTT), a food-motivated test that quantifies attention. We also compared the binding profiles of salvA and ketamine at KORs and NMDA receptors.
SalvA and ketamine produced the same pattern of disruptive effects in the 5CSRTT, characterized by increases in signs often associated with reduced motivation (omission errors) and deficits in processing (elevated latencies to respond correctly). Sessions in which rats were fed before testing suggest that reduced motivation produces a subtly different pattern of behavior. Pretreatment with the KOR antagonist JDTic (10 mg/kg) blocked all salvA effects and some ketamine effects. Binding and function studies revealed that ketamine is a full agonist at KORs, although not as potent or selective as salvA.
SalvA and ketamine have previously under-appreciated similarities in their behavioral effects and pharmacological profiles. By implication, KORs might be involved in some of the cognitive abnormalities observed in psychiatric disorders such as schizophrenia.
C1 [Carlezon, William A., Jr.] McLean Hosp, Dept Psychiat, MRC 217, Belmont, MA 02478 USA.
[Nemeth, Christina L.; Paine, Tracie A.; Beguin, Cecile; Cohen, Bruce M.; Carlezon, William A., Jr.] Harvard Univ, Sch Med, McLean Hosp, Behav Genet Lab,Dept Psychiat, Belmont, MA 02478 USA.
[Rittiner, Joseph E.; Roth, Bryan L.] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA.
[Rittiner, Joseph E.; Roth, Bryan L.] Univ N Carolina, Sch Med, NIMH Psychoact Drug Screening Program, Chapel Hill, NC 27599 USA.
[Carroll, F. Ivy] Res Triangle Inst, Res Triangle Pk, NC 27709 USA.
RP Carlezon, WA (reprint author), McLean Hosp, Dept Psychiat, MRC 217, 115 Mill St, Belmont, MA 02478 USA.
EM bcarlezon@mclean.harvard.edu
RI Roth, Bryan/F-3928-2010
FU National Institute of Mental Health [MH063266, RO1DA017204]
FX This study is supported by the National Institute of Mental Health
(MH063266 to WAC, and RO1DA017204 to BLR).
NR 58
TC 30
Z9 31
U1 0
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD JUN
PY 2010
VL 210
IS 2
SI SI
BP 263
EP 274
DI 10.1007/s00213-010-1834-7
PG 12
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 592XW
UT WOS:000277416300016
PM 20358363
ER
PT J
AU Fields, D
AF Fields, Douglas
TI Non-vesicular release of ATP from axons firing action potentials
SO PURINERGIC SIGNALLING
LA English
DT Meeting Abstract
C1 [Fields, Douglas] NICHD, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1573-9538
J9 PURINERG SIGNAL
JI Purinergic Signal.
PD JUN
PY 2010
VL 6
SU 1
BP 13
EP 13
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 630AA
UT WOS:000280241700027
ER
PT J
AU Jacobson, KA
AF Jacobson, Kenneth A.
TI New frontiers for ligands of adenosine and P2Y receptors
SO PURINERGIC SIGNALLING
LA English
DT Meeting Abstract
C1 [Jacobson, Kenneth A.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1573-9538
J9 PURINERG SIGNAL
JI Purinergic Signal.
PD JUN
PY 2010
VL 6
SU 1
BP 14
EP 15
PG 2
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 630AA
UT WOS:000280241700030
ER
PT J
AU Gonzalez, SF
AF Gonzalez, Sergi Ferre
TI Receptor heteromerization determines the striatal pre- and postsynaptic
profile of adenosine A2A receptor antagonists
SO PURINERGIC SIGNALLING
LA English
DT Meeting Abstract
C1 [Gonzalez, Sergi Ferre] NIDA, IRP, NIH, DHHS, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1573-9538
J9 PURINERG SIGNAL
JI Purinergic Signal.
PD JUN
PY 2010
VL 6
SU 1
BP 18
EP 19
PG 2
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 630AA
UT WOS:000280241700039
ER
PT J
AU Schiffmann, S
Gall, D
Ferre, S
Azdad, K
AF Schiffmann, Serge
Gall, David
Ferre, Sergi
Azdad, Karima
TI Dopamine D2 and adenosine A2A receptors regulate activity of
striatopallidal neurons through A2A-D2 receptor heteromerization
SO PURINERGIC SIGNALLING
LA English
DT Meeting Abstract
C1 [Schiffmann, Serge; Gall, David; Azdad, Karima] Univ Libre Bruxelles, Neurophysiol Lab, Brussels, Belgium.
[Ferre, Sergi] Natl Inst Drug Abuse, Behav Neurosci Branch, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1573-9538
J9 PURINERG SIGNAL
JI Purinergic Signal.
PD JUN
PY 2010
VL 6
SU 1
BP 19
EP 20
PG 2
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 630AA
UT WOS:000280241700041
ER
PT J
AU Brugal, GN
Ferre, S
Cordomi, A
Moreno, E
Mallol, J
Cacado, V
Cortes, A
Hoffmann, H
Ortiz, J
Canela, EI
Lluis, C
Pardo, L
Franco, R
Woods, AS
AF Navarro Brugal, Gemma
Ferre, Sergi
Cordomi, Arnau
Moreno, Estefania
Mallol, Josefa
Cacado, Vicent
Cortes, Antoni
Hoffmann, Hanne
Ortiz, Jordi
Canela, Enric I.
Lluis, Carme
Pardo, Leonardo
Franco, Rafael
Woods, Amina S.
TI Electrostatic Interactions as key determinants of the quaternary
structure of receptor heteromers
SO PURINERGIC SIGNALLING
LA English
DT Meeting Abstract
C1 [Navarro Brugal, Gemma; Moreno, Estefania; Mallol, Josefa; Cacado, Vicent; Cortes, Antoni; Canela, Enric I.; Lluis, Carme; Franco, Rafael] Univ Barcelona, Dept Bioquim & Biol Mol, E-08007 Barcelona, Spain.
[Ferre, Sergi; Woods, Amina S.] NIDA, NIH, Bethesda, MD USA.
[Hoffmann, Hanne; Ortiz, Jordi] Univ Autonoma Barcelona, Barcelona, Spain.
RI Franco, Rafael/C-3694-2015
OI Franco, Rafael/0000-0003-2549-4919
NR 0
TC 0
Z9 0
U1 1
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1573-9538
J9 PURINERG SIGNAL
JI Purinergic Signal.
PD JUN
PY 2010
VL 6
SU 1
BP 38
EP 38
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 630AA
UT WOS:000280241700081
ER
PT J
AU Schiffmann, S
Gall, D
Ferre, S
Azdad, K
AF Schiffmann, Serge
Gall, David
Ferre, Sergi
Azdad, Karima
TI Dopamine D2 and adenosine A2A receptors regulate activity of
striatopallidal neurons through A2A-D2 receptor heteromerization
SO PURINERGIC SIGNALLING
LA English
DT Meeting Abstract
C1 [Schiffmann, Serge; Gall, David; Azdad, Karima] Univ Libre Bruxelles, Neurophysiol Lab, Brussels, Belgium.
[Ferre, Sergi] NIDA, Behav Neurosci Branch, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1573-9538
J9 PURINERG SIGNAL
JI Purinergic Signal.
PD JUN
PY 2010
VL 6
SU 1
BP 98
EP 99
PG 2
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 630AA
UT WOS:000280241700210
ER
PT J
AU Daniele, S
Fumagalli, M
Lee, PR
Trincavelli, ML
Lecca, D
Fields, RD
Verderio, C
Abbracchio, MP
Martini, C
AF Daniele, Simona
Fumagalli, Marta
Lee, Philip R.
Trincavelli, Maria Letizia
Lecca, Davide
Fields, R. Douglas
Verderio, Claudia
Abbracchio, Maria Pia
Martini, Claudia
TI The P2Y-like GPR17 receptor orchestrates the transition between immature
and myelinating oligodendrocytes and is a new target for myelin repair
SO PURINERGIC SIGNALLING
LA English
DT Meeting Abstract
C1 [Daniele, Simona; Trincavelli, Maria Letizia; Martini, Claudia] Univ Pisa, Dept Psychiat Neurobiol Pharmacol & Biotechnol, I-56100 Pisa, Italy.
[Fumagalli, Marta; Lecca, Davide; Abbracchio, Maria Pia] Univ Milan, Dept Pharmacol Sci, I-20122 Milan, Italy.
[Lee, Philip R.; Fields, R. Douglas] NIH, Nervous Syst Dev & Plast Sect, Bethesda, MD USA.
[Verderio, Claudia] Univ Milan, CNR, Inst Neurosci, I-20122 Milan, Italy.
RI Lecca, Davide/A-8850-2010; Abbracchio, Maria Pia/B-9342-2014; Verderio,
Claudia/K-4415-2016
OI Lecca, Davide/0000-0002-3258-363X; Abbracchio, Maria
Pia/0000-0002-7833-3388; Verderio, Claudia/0000-0001-7216-5873
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1573-9538
J9 PURINERG SIGNAL
JI Purinergic Signal.
PD JUN
PY 2010
VL 6
SU 1
BP 128
EP 129
PG 2
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 630AA
UT WOS:000280241700271
ER
PT J
AU Kumar, TS
Zhou, SY
Joshi, BV
Ramachandran, R
Yang, TH
Liang, BT
Jacobson, KA
AF Kumar, T. Santhosh
Zhou, Si-Yuan
Joshi, Bhalchandra V.
Ramachandran, Ramachandran
Yang, Tiehong
Liang, Bruce T.
Jacobson, Kenneth A.
TI Structure-activity relationship of (N)-methanocarba phosphonate
analogues of 5 '-AMP as cardioprotective agents acting through a cardiac
P2X receptor
SO PURINERGIC SIGNALLING
LA English
DT Meeting Abstract
C1 [Kumar, T. Santhosh; Joshi, Bhalchandra V.; Ramachandran, Ramachandran; Jacobson, Kenneth A.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Zhou, Si-Yuan; Yang, Tiehong; Liang, Bruce T.] Univ Connecticut, Ctr Hlth, Pat & Jim Calhoun Cardiol Ctr, Storrs, CT 06269 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1573-9538
J9 PURINERG SIGNAL
JI Purinergic Signal.
PD JUN
PY 2010
VL 6
SU 1
BP 143
EP 144
PG 2
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 630AA
UT WOS:000280241700302
ER
PT J
AU Keene, AM
Balasubramanian, R
Lloyd, J
Shainberg, A
Jacobson, KA
AF Keene, Athena M.
Balasubramanian, Ramachandran
Lloyd, John
Shainberg, Asher
Jacobson, Kenneth A.
TI Multivalent dendrimeric and monomeric adenosine agonists attenuate cell
death
SO PURINERGIC SIGNALLING
LA English
DT Meeting Abstract
C1 [Keene, Athena M.; Balasubramanian, Ramachandran; Lloyd, John; Jacobson, Kenneth A.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Shainberg, Asher] Bar Ilan Univ, Fac Life Sci, IL-52100 Ramat Gan, Israel.
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1573-9538
J9 PURINERG SIGNAL
JI Purinergic Signal.
PD JUN
PY 2010
VL 6
SU 1
BP 144
EP 144
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 630AA
UT WOS:000280241700303
ER
PT J
AU Ceruti, SM
Calleri, E
Cristalli, G
Martini, C
Temporini, C
Parravicini, C
Volpini, R
Daniele, S
Caccialanza, G
Lecca, D
Lambertucci, C
Trincavelli, ML
Marucci, G
Wainer, IW
Ranghino, G
Fantucci, P
Abbracchio, MP
Massolini, G
AF Ceruti, Stefania Maria
Calleri, Enrica
Cristalli, Gloria
Martini, Claudia
Temporini, Caterina
Parravicini, Chiara
Volpini, Rosaria
Daniele, Simona
Caccialanza, Gabriele
Lecca, Davide
Lambertucci, Catia
Trincavelli, Maria Letizia
Marucci, Gabriella
Wainer, Irwing W.
Ranghino, Graziella
Fantucci, Piercarlo
Abbracchio, Maria P.
Massolini, Gabriella
TI Frontal affinity chromatography-mass spectrometry useful for
characterization of new ligands for GPR17 receptor
SO PURINERGIC SIGNALLING
LA English
DT Meeting Abstract
C1 [Ceruti, Stefania Maria; Parravicini, Chiara; Lecca, Davide; Abbracchio, Maria P.] Univ Milan, Dept Pharmacol Sci, I-20122 Milan, Italy.
[Calleri, Enrica; Temporini, Caterina; Caccialanza, Gabriele; Massolini, Gabriella] Univ Pavia, Dept Pharmaceut Chem, I-27100 Pavia, Italy.
[Cristalli, Gloria; Volpini, Rosaria; Lambertucci, Catia; Marucci, Gabriella] Univ Camerino, Dept Chem Sci, I-62032 Camerino, Italy.
[Martini, Claudia; Daniele, Simona; Trincavelli, Maria Letizia] Univ Pisa, Dept Psychiat Neurobiol Pharmacol & Biotechnol, I-56100 Pisa, Italy.
[Wainer, Irwing W.] NIH, Gerontol Res Ctr, Bethesda, MD USA.
[Fantucci, Piercarlo] Univ Milano Bicocca, Dept Biosci & Biotechnol, Milan, Italy.
RI Lecca, Davide/A-8850-2010; Abbracchio, Maria Pia/B-9342-2014
OI Lecca, Davide/0000-0002-3258-363X; Abbracchio, Maria
Pia/0000-0002-7833-3388
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1573-9538
J9 PURINERG SIGNAL
JI Purinergic Signal.
PD JUN
PY 2010
VL 6
SU 1
BP 147
EP 148
PG 2
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 630AA
UT WOS:000280241700310
ER
PT J
AU Goldman-Nedergaard, N
Chen, M
Fujita, T
Xu, QW
Chen, JF
Schnermann, J
Takano, T
Bekar, L
Tieu, K
Nedergaard, M
AF Goldman-Nedergaard, Nanna
Chen, Michael
Fujita, Takumi
Xu, Qiwu
Chen, Jiang-Fan
Schnermann, Jurgen
Takano, Takahiro
Bekar, Lane
Tieu, Kim
Nedergaard, Maiken
TI The analgesic effect of acupuncture is mediated by adenosine A1
receptors
SO PURINERGIC SIGNALLING
LA English
DT Meeting Abstract
C1 [Goldman-Nedergaard, Nanna; Chen, Michael; Fujita, Takumi; Xu, Qiwu; Takano, Takahiro; Bekar, Lane; Tieu, Kim; Nedergaard, Maiken] Univ Rochester, Ctr Translat Neuromed, Rochester, NY 14627 USA.
[Chen, Jiang-Fan] Boston Univ, Dept Neurol, Boston, MA 02215 USA.
[Schnermann, Jurgen] NIH, NIDDK, Bethesda, MD USA.
NR 3
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1573-9538
J9 PURINERG SIGNAL
JI Purinergic Signal.
PD JUN
PY 2010
VL 6
SU 1
BP 161
EP 162
PG 2
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 630AA
UT WOS:000280241700338
ER
PT J
AU Gershon, R
Rothrock, NE
Hanrahan, RT
Jansky, LJ
Harniss, M
Riley, W
AF Gershon, Richard
Rothrock, Nan E.
Hanrahan, Rachel T.
Jansky, Liz J.
Harniss, Mark
Riley, William
TI The development of a clinical outcomes survey research application:
Assessment Center(SM)
SO QUALITY OF LIFE RESEARCH
LA English
DT Article
DE Software; Software design; Outcome assessment (health care);
Psychometrics; Quality of life; Health surveys; Questionnaires
ID ITEM BANKING; NIH ROADMAP
AB Introduction The National Institutes of Health sponsored Patient-Reported Outcome Measurement Information System (PROMIS) aimed to create item banks and computerized adaptive tests (CATs) across multiple domains for individuals with a range of chronic diseases.
Purpose Web-based software was created to enable a researcher to create study-specific Websites that could administer PROMIS CATs and other instruments to research participants or clinical samples. This paper outlines the process used to develop a user-friendly, free, Web-based resource (Assessment Center(SM)) for storage, retrieval, organization, sharing, and administration of patient-reported outcomes (PRO) instruments.
Methods Joint Application Design (JAD) sessions were conducted with representatives from numerous institutions in order to supply a general wish list of features. Use Cases were then written to ensure that end user expectations matched programmer specifications. Program development included daily programmer "scrum'' sessions, weekly Usability Acceptability Testing (UAT) and continuous Quality Assurance (QA) activities pre-and post-release.
Results Assessment Center includes features that promote instrument development including item histories, data management, and storage of statistical analysis results.
Conclusions This case study of software development highlights the collection and incorporation of user input throughout the development process. Potential future applications of Assessment Center in clinical research are discussed.
C1 [Gershon, Richard; Rothrock, Nan E.; Hanrahan, Rachel T.] Northwestern Univ, Dept Med Social Sci, Chicago, IL 60611 USA.
[Jansky, Liz J.] Westat Corp, Rockville, MD USA.
[Harniss, Mark] Univ Washington, Seattle, WA 98195 USA.
[Riley, William] NHLBI, Bethesda, MD 20892 USA.
RP Gershon, R (reprint author), Northwestern Univ, Dept Med Social Sci, 625 N Michigan Ave,Suite 2700, Chicago, IL 60611 USA.
EM gershon@northwestern.edu; n-rothrock@northwestern.edu
RI Harniss, Mark/J-3118-2013
OI Harniss, Mark/0000-0002-7741-2498
FU National Institutes of Health; Patient-Reported Outcomes Measurement
Information System (PROMIS) [U01 AR052177]; Neurological Quality of Life
(Neuro-QOL) [HHSN 2652004236-01C]; Refining and Standardizing Health
Literacy Assessment [RO1 HL081485-03]
FX Primary funding for the Assessment Center application has been provided
as part of several federally funded projects sponsored by the National
Institutes of Health including the Patient-Reported Outcomes Measurement
Information System (PROMIS; U01 AR052177), Neurological Quality of Life
(Neuro-QOL; HHSN 2652004236-01C), Refining and Standardizing Health
Literacy Assessment (RO1 HL081485-03), the NIH Toolbox for the
Assessment of Neurological and Behavioral Function (AG-260-0601) and a
recent award as the PROMIS Technology Center (U54AR057943). The authors
would like to acknowledge the editorial assistance of Lani Gershon.
NR 29
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U1 2
U2 6
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-9343
J9 QUAL LIFE RES
JI Qual. Life Res.
PD JUN
PY 2010
VL 19
IS 5
BP 677
EP 685
DI 10.1007/s11136-010-9634-4
PG 9
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 610LZ
UT WOS:000278735600008
PM 20306332
ER
PT J
AU Chen, X
Del Vecchio, S
AF Chen, X.
Del Vecchio, S.
TI Molecular imaging of tumor microenvironment FOREWORD
SO QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
LA English
DT Editorial Material
C1 [Chen, X.] NIBIB, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
[Del Vecchio, S.] Univ Naples Federico 2, Dept Biomorphol & Funct Sci, Inst Biostruct & Bioimages, CNR, I-80131 Naples, Italy.
RP Chen, X (reprint author), NIBIB, Lab Mol Imaging & Nanomed, NIH, 31 Ctr Dr,Suite 1014, Bethesda, MD 20892 USA.
EM shawn.chen@nih.gov; delvecc@unina.it
NR 0
TC 0
Z9 0
U1 0
U2 1
PU EDIZIONI MINERVA MEDICA
PI TURIN
PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY
SN 1824-4785
J9 Q J NUCL MED MOL IM
JI Q. J. Nucl. Med. Mol. Imag.
PD JUN
PY 2010
VL 54
IS 3
BP 243
EP 243
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 683SU
UT WOS:000284496300001
PM 20639810
ER
PT J
AU Zhu, L
Niu, G
Fang, X
Chen, X
AF Zhu, L.
Niu, G.
Fang, X.
Chen, X.
TI Preclinical molecular imaging of tumor angiogenesis
SO QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
LA English
DT Article
DE Angiogenesis; Molecular imaging; Vascular endothelial growth factor
receptor-1; Integrin alphaVbeta3; Matrix metalloproteinases
ID ENDOTHELIAL GROWTH-FACTOR; POSITRON-EMISSION-TOMOGRAPHY; INTEGRIN
ALPHA(V)BETA(3) EXPRESSION; SQUAMOUS-CELL CARCINOMA;
MATRIX-METALLOPROTEINASE EXPRESSION; CANCER ALPHA(V)-INTEGRIN
EXPRESSION; RECEPTOR TYROSINE KINASES; IN-VIVO CHARACTERIZATION; CYCLIC
RGD PEPTIDES; SMALL-ANIMAL PET
AB Angiogenesis, a course that new blood vessels grow from the existing vasculature, plays important roles both physiologically and pathologically. Angiogenesis can be switched on by growth factors secreted by tumor cells, and in turn supplies more oxygen and nutrition to the tumor. More and more preclinical studies and clinical trials have shown that inhibition of angiogenesis is an effective way to inhibit tumor growth, substantiating the development of anti-angiogenesis therapeutics. Imaging technologies accelerate the translation of preclinical research to the clinic. In oncology, various imaging modalities are widely applied to drug development, tumor early detection and therapy response monitoring. So far, several angiogenesis related imaging agents are promising in cancer diagnosis. However, more effective imaging agents with less side-effect still need to be pursued to visualize angiogenesis process non-invasively. The main purpose of this review is to summarize the recent progresses in preclinical molecular imaging of angiogenesis and to discuss the potential of the current preclinical probes specific to various angiogenesis targets including vascular endothelial growth factor and its receptors (VEGF/VEGFRs), integrin alpha v beta 3 and matrix metalloproteinases (MMPs). It is predicable that related investigations in the field will benefit cancer research and quicken the anti-angiogenic drug development.
C1 [Zhu, L.; Niu, G.; Chen, X.] NIBIB, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
[Zhu, L.; Fang, X.] Jilin Univ, Coll Life Sci, Changchun 130023, Peoples R China.
[Niu, G.] NIBIB, Imaging Sci Training Program, Radiol & Imaging Sci Clin Ctr, Bethesda, MD 20892 USA.
RP Chen, X (reprint author), NIBIB, Lab Mol Imaging & Nanomed, NIH, 31 Ctr Dr,Suite 1C14, Bethesda, MD 20892 USA.
EM shawn.chen@nih.gov
FU China Scholarship Council (CSC); Radiology and Imaging Sciences
Department, NIH Clinical Center and the Intramural
FX L. Zhu is partially supported by the scholarship from China Scholarship
Council (CSC). G. Niu is an Imaging Sciences Training Fellowship jointly
supported by the Radiology and Imaging Sciences Department, NIH Clinical
Center and the Intramural
NR 187
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U1 1
U2 3
PU EDIZIONI MINERVA MEDICA
PI TURIN
PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY
SN 1824-4785
J9 Q J NUCL MED MOL IM
JI Q. J. Nucl. Med. Mol. Imag.
PD JUN
PY 2010
VL 54
IS 3
BP 291
EP 308
PG 18
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 683SU
UT WOS:000284496300006
PM 20639815
ER
PT J
AU Fay, MP
AF Fay, Michael P.
TI Two-sided Exact Tests and Matching Confidence Intervals for Discrete
Data
SO R JOURNAL
LA English
DT Article
AB There is an inherent relationship between two-sided hypothesis tests and confidence intervals. A series of two-sided hypothesis tests may be inverted to obtain the matching 100(1-alpha)% confidence interval defined as the smallest interval that contains all point null parameter values that would not be rejected at the alpha level. Unfortunately, for discrete data there are several different ways of defining two-sided exact tests and the most commonly used two-sided exact tests are defined one way, while the most commonly used exact confidence intervals are inversions of tests defined another way. This can lead to inconsistencies where the exact test rejects but the exact confidence interval contains the null parameter value. The packages exactci and exact2x2 provide several exact tests with the matching confidence intervals avoiding these inconsistencies as much as possible. Examples are given for binomial and Poisson parameters and both paired and unpaired 2 x 2 tables.
C1 NIAID, Bethesda, MD 20817 USA.
RP Fay, MP (reprint author), NIAID, 6700-A Rockledge Dr,Room 5133, Bethesda, MD 20817 USA.
EM mfay@niaid.nih.gov
OI Fay, Michael P./0000-0002-8643-9625
NR 11
TC 38
Z9 38
U1 0
U2 2
PU R FOUNDATION STATISTICAL COMPUTING
PI WIEN
PA WIRTSCHAFTSUNIVERSITAT, INST STATISTICS & MATHEMATICS, AUGASSE 2-6,
WIEN, 1090, AUSTRIA
SN 2073-4859
J9 R J
JI R Journal
PD JUN
PY 2010
VL 2
IS 1
BP 53
EP 58
PG 6
WC Computer Science, Interdisciplinary Applications; Statistics &
Probability
SC Computer Science; Mathematics
GA V27BY
UT WOS:000208589900009
ER
PT J
AU Summers, RM
AF Summers, Ronald M.
TI Polyp Size Measurement at CT Colonography: What Do We Know and What Do
We Need to Know?
SO RADIOLOGY
LA English
DT Review
ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; COLONIC POLYPS; IN-VITRO;
COLORECTAL-CANCER; AUTOMATED MEASUREMENT; VIRTUAL COLONOSCOPY;
HYPERPLASTIC POLYPS; NATURAL-HISTORY; OPTICAL COLONOSCOPY; ADENOMATOUS
POLYPS
AB Polyp size is a critical biomarker for clinical management. Larger polyps have a greater likelihood of being or of becoming an adenocarcinoma. To balance the referral rate for polypectomy against the risk of leaving potential cancers in situ, sizes of 6 and 10 mm are increasingly being discussed as critical thresholds for clinical decision making (immediate polypectomy versus polyp surveillance) and have been incorporated into the consensus CT Colonography Reporting and Data System (C-RADS). Polyp size measurement at optical colonoscopy, pathologic examination, and computed tomographic (CT) colonography has been studied extensively but the reported precision, accuracy, and relative sizes have been highly variable. Sizes measured at CT colonography tend to lie between those measured at optical colonoscopy and pathologic evaluation. The size measurements are subject to a variety of sources of error associated with image acquisition, display, and interpretation, such as partial volume averaging, two-versus three-dimensional displays, and observer variability. This review summarizes current best practices for polyp size measurement, describes the role of automated size measurement software, discusses how to manage the measurement uncertainties, and identifies areas requiring further research.
C1 NIH, Imaging Biomarkers & Comp Aided Diag Lab, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
RP Summers, RM (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Dept Radiol & Imaging Sci, Ctr Clin, Bldg 10,Room 1C368X,MSC 1182, Bethesda, MD 20892 USA.
EM rms@nih.gov
FU National Institutes of Health Clinical Center [Z01 CL040003]
FX This research was supported by the intramural research program of the
National Institutes of Health Clinical Center (project Z01 CL040003).
NR 78
TC 29
Z9 33
U1 0
U2 1
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 JUN
PY 2010
VL 255
IS 3
BP 707
EP 720
DI 10.1148/radiol.10090877
PG 14
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 601DO
UT WOS:000278038500008
PM 20501711
ER
PT J
AU Kokkinaki, M
Lee, TL
He, ZP
Jiang, JJ
Golestaneh, N
Hofmann, MC
Chan, WY
Dym, M
AF Kokkinaki, Maria
Lee, Tin-Lap
He, Zuping
Jiang, Jiji
Golestaneh, Nady
Hofmann, Marie-Claude
Chan, Wai-Yee
Dym, Martin
TI Age affects gene expression in mouse spermatogonial stem/progenitor
cells
SO REPRODUCTION
LA English
DT Article
ID COLONY-STIMULATING FACTOR-1; ADVANCING PATERNAL AGE; LINE STEM-CELLS;
SELF-RENEWAL; UNDIFFERENTIATED SPERMATOGONIA; NEUROTROPHIC FACTOR; SEMEN
QUALITY; NICHE; AUTISM; TESTIS
AB Spermatogenesis in man starts with spermatogonial stem cells (SSCs), and leads to the production of sperm in similar to 64 days, common to old and young men. Sperm from elderly men are functional and able to fertilize eggs and produce offspring, even though daily sperm production is more than 50% lower and damage to sperm DNA is significantly higher in older men than in those who are younger. Our hypothesis is that the SSC/spermatogonial progenitors themselves age. To test this hypothesis, we studied the gene expression profile of mouse SSC/progenitor cells at several ages using microarrays. After sequential enzyme dispersion, we purified the SSC/progenitors with immunomagnetic cell sorting using an antibody to GFRA1, a known SSC/progenitor cell marker. RNA was isolated and used for the in vitro synthesis of amplified and labeled cRNAs that were hybridized to the Affymetrix mouse genome microarrays. The experiments were repeated twice with different cell preparations, and statistically significant results are presented. Quantitative RT-PCR analysis was used to confirm the microarray results. Comparison of four age groups (6 days, 21 days, 60 days, and 8 months old) showed a number of genes that were expressed specifically in the older mice. Two of them (i.e. Icam1 and Selp) have also been shown to mark aging hematopoietic stem cells. On the other hand, the expression levels of the genes encoding the SSC markers Gfra1 and Plzf did not seem to be significantly altered by age, indicating that age affects only certain SSC/progenitor properties. Reproduction (2010) 139 1011-1020
C1 [Kokkinaki, Maria; He, Zuping; Jiang, Jiji; Golestaneh, Nady; Chan, Wai-Yee; Dym, Martin] Georgetown Univ, Med Ctr, Dept Biochem & Mol & Cellular Biol, Washington, DC 20057 USA.
[Lee, Tin-Lap; Chan, Wai-Yee] NICHHD, NIH, Bethesda, MD 20892 USA.
[Hofmann, Marie-Claude] Univ Illinois, Dept Vet Biosci, Urbana, IL 61802 USA.
RP Dym, M (reprint author), Georgetown Univ, Med Ctr, Dept Biochem & Mol & Cellular Biol, 3900 Reservoir Rd NW, Washington, DC 20057 USA.
EM dymm@georgetown.edu
RI Lee, Tin-Lap/A-7853-2009
OI Lee, Tin-Lap/0000-0002-6654-0988
FU National Institutes of Health (NIH) [HD044543, HD033728]; Eunice Kennedy
Shriver National Institute of Child Health and Human Development
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (NIH), Eunice Kennedy Shriver National
Institute of Child Health and Human Development (W-Y Chan), and NIH
grants HD044543 (M-C Hofmann) and HD033728 (M Dym).
NR 53
TC 16
Z9 17
U1 1
U2 3
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 JUN
PY 2010
VL 139
IS 6
BP 1011
EP 1020
DI 10.1530/REP-09-0566
PG 10
WC Developmental Biology; Reproductive Biology
SC Developmental Biology; Reproductive Biology
GA 597SK
UT WOS:000277781400008
PM 20371641
ER
PT J
AU Chen, L
Bi, JJ
Nakai, M
Bunick, D
Couse, JF
Korach, KS
Nowak, RA
AF Chen, Li
Bi, Jiajia
Nakai, Masaaki
Bunick, David
Couse, John F.
Korach, Kenneth S.
Nowak, Romana A.
TI Expression of basigin in reproductive tissues of estrogen receptor-alpha
or -beta null mice
SO REPRODUCTION
LA English
DT Article
ID MATRIX METALLOPROTEINASE INDUCER; ADULT MALE-MOUSE; IMMUNOGLOBULIN
SUPERFAMILY; EFFERENT DUCTULES; CYCLOPHILIN-A; CELLS; GENE; MEMBER;
LACKING; CD147
AB Basigin plays important roles in both male and female reproduction because basigin (Bsg) null male and female mice are infertile. The aim of the present study was to determine whether basigin expression in reproductive organs requires estrogen receptor-alpha (ESR1, ER alpha) or -beta (ESR2, ER beta). Expression of basigin protein in the testis, ovary, and male and female reproductive tracts was studied in adult wild-type (WT), Esr1-null (alpha ERKO), and Esr2-null (beta ERKO) mice by immunohistochemistry and immunoblotting. Basigin mRNA levels in ovary and uterus were examined by quantitative RT-PCR. In females, basigin protein expression was observed mainly in granulosa and interstitial cells of the ovary and epithelial cells of the proximal oviduct in all genotypes. Basigin protein was also expressed in the uterine epithelium at proestrus and estrus in WT and beta ERKO mice but not in alpha ERKO mice. However, a higher level of basigin mRNA was observed in uteri of alpha ERKO mice compared with WT and beta ERKO mice. In males, basigin was expressed in Leydig cells and all germ cells except spermatogonia in all genotypes. Basigin was present in epithelial cells lining the efferent ductules in WT and beta ERKO mice, but expression was greatly reduced in alpha ERKO mice. In epididymal ducts, basigin expression was observed in epithelial cells in the caput and cauda in all genotypes. These data suggest that expression of basigin protein requires ESR1, but not ESR2, in the uterus and efferent ductules, but is independent of estrogen receptor in the ovary, oviduct, testis, and epididymis. Reproduction (2010) 139 1057-1066
C1 [Chen, Li; Bi, Jiajia; Nakai, Masaaki; Nowak, Romana A.] Univ Illinois, Dept Anim Sci, Urbana, IL 61801 USA.
[Bunick, David] Univ Illinois, Dept Vet Biosci, Urbana, IL 61801 USA.
[Couse, John F.; Korach, Kenneth S.] Natl Inst Environm Hlth Sci, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA.
RP Nowak, RA (reprint author), Univ Illinois, Dept Anim Sci, 328 Mumford Hall, Urbana, IL 61801 USA.
EM ranowak@uiuc.edu
OI Korach, Kenneth/0000-0002-7765-418X
FU Eunice Kennedy Shriver NICHD/NIH [U54 HD40093]
FX This research was supported by the Eunice Kennedy Shriver NICHD/NIH
through cooperative agreement (U54 HD40093) as part of the Specialized
Cooperative Centers Program in Reproduction and Infertility Research.
NR 45
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U2 1
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 JUN
PY 2010
VL 139
IS 6
BP 1057
EP 1066
DI 10.1530/REP-10-0069
PG 10
WC Developmental Biology; Reproductive Biology
SC Developmental Biology; Reproductive Biology
GA 597SK
UT WOS:000277781400013
PM 20388736
ER
PT J
AU Bloom, MS
Parsons, PJ
Steuerwald, A
Schisterman, EF
Browne, RW
Kim, K
Coccaro, GA
Conti, GC
Narayan, N
Fujimoto, VY
AF Bloom, Michael S.
Parsons, Patrick J.
Steuerwald, Amyl
Schisterman, Enrique F.
Browne, Richard W.
Kim, Keewan
Coccaro, Gregory A.
Conti, Giulia C.
Narayan, Natasha
Fujimoto, Victor Y.
TI Toxic trace metals and human oocytes during in vitro fertilization (IVF)
SO REPRODUCTIVE TOXICOLOGY
LA English
DT Article
DE Mercury (Hg); Cadmium (Cd); Lead (Pb); Oocyte maturation; Oocyte
fertilization; In vitro fertilization (IVF); Assisted reproductive
technologies (ART); Intracytoplasmic sperm injection (ICSI)
ID PLASMA-MASS SPECTROMETRY; SEMINAL PLASMA; FOLLICULAR-FLUID;
ENVIRONMENTAL CONTAMINANTS; ARTIFICIAL-INSEMINATION; MAMMALIAN OOCYTE;
HEAVY-METALS; LEAD; CADMIUM; MERCURY
AB Trace exposures to the toxic metals mercury (Hg), cadmium (Cd) and lead (Pb) may threaten human reproductive health. The aim of this study is to generate biologically-plausible hypotheses concerning associations between Hg, Cd, and Pb and in vitro fertilization (IVF) endpoints. For 15 female IVF patients, a multivariable log-binomial model suggests a 75% reduction in the probability for a retrieved oocyte to be in metaphase-II arrest for each mu g/dL increase in blood Pb concentration (relative risk (RR) = 0.25,95% confidence interval (CI) 0.03-2.50, P=0.240). For 15 male IVF partners, each mu g/L. increase in urine Cd concentration is associated with an 81% decrease in the probability for oocyte fertilization (RR = 0.19,95% CI 0.03-1.35, P=0.097). Because of the magnitude of the effects, these results warrant a comprehensive study with sufficient statistical power to further evaluate these hypotheses. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Bloom, Michael S.] SUNY Albany, Dept Environm Hlth Sci, Sch Publ Hlth, Rensselaer, NY 12144 USA.
[Kim, Keewan] SUNY Albany, Dept Epidemiol & Biostat, Rensselaer, NY 12144 USA.
[Coccaro, Gregory A.] SUNY Albany, Dept Biomed Sci, Rensselaer, NY 12144 USA.
[Parsons, Patrick J.; Steuerwald, Amyl] New York State Dept Hlth, Lab Inorgan & Nucl Chem, Wadsworth Ctr, Albany, NY USA.
[Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Rockville, MD USA.
[Browne, Richard W.] SUNY Buffalo, Dept Biotech & Clin Lab Sci, Buffalo, NY 14260 USA.
[Conti, Giulia C.; Narayan, Natasha; Fujimoto, Victor Y.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA.
RP Bloom, MS (reprint author), SUNY Albany, Dept Environm Hlth Sci, Sch Publ Hlth, Rm 153,1 Univ Pl, Rensselaer, NY 12144 USA.
EM mbloom@uamail.albany.edu
OI Parsons, Patrick/0000-0001-9133-875X; Schisterman,
Enrique/0000-0003-3757-641X; Bloom, Michael/0000-0002-0028-5494; Kim,
Keewan/0000-0002-1892-6739
FU NIH; Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX We would like to thank Chris D. Palmer, Ph.D., for providing expert
input regarding analysis of metals in blood specimens and to extend our
gratitude to the study participants whose generosity made this study
possible. This work was not supported by any external grant funding.
Institutional discretionary research funds available to Drs. Bloom and
Fujimoto were used to support this work. This research was also
supported in part by the Intramural Research Program of the NIH, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development.
NR 61
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U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0890-6238
J9 REPROD TOXICOL
JI Reprod. Toxicol.
PD JUN
PY 2010
VL 29
IS 3
BP 298
EP 305
DI 10.1016/j.reprotox.2010.01.003
PG 8
WC Reproductive Biology; Toxicology
SC Reproductive Biology; Toxicology
GA 588ZB
UT WOS:000277112200007
PM 20096775
ER
PT J
AU Tudor-Locke, C
McClain, JJ
Hart, TL
Sisson, SB
Washington, TL
AF Tudor-Locke, Catrine
McClain, James J.
Hart, Teresa L.
Sisson, Susan B.
Washington, Tracy L.
TI Response to A Step in the Right Direction: Commentary on Expected Values
for Pedometer-Determined Physical Activity in Youth
SO RESEARCH QUARTERLY FOR EXERCISE AND SPORT
LA English
DT Editorial Material
DE accelerometer; exercise; objective monitoring; walking
C1 [Tudor-Locke, Catrine] Pennington Biomed Res Ctr, Walking Behav Lab, Baton Rouge, LA 70808 USA.
[McClain, James J.] NCI, Baltimore, MD USA.
[Hart, Teresa L.] Univ Wisconsin Milwaukee, Coll Hlth Sci, Milwaukee, WI 53201 USA.
[Sisson, Susan B.] Univ Oklahoma, Hlth Sci Ctr, Dept Nutr Sci, Norman, OK 73019 USA.
[Washington, Tracy L.] Arizona State Univ, Coll Nursing, Tempe, AZ 85287 USA.
RP Tudor-Locke, C (reprint author), Pennington Biomed Res Ctr, Walking Behav Lab, 6400 Perkins Rd, Baton Rouge, LA 70808 USA.
EM Tudor-Locke@pbrc.edu
OI Washington, Tracy L./0000-0002-0959-7320
NR 2
TC 0
Z9 0
U1 0
U2 4
PU AMER ALLIANCE HEALTH PHYS EDUC REC & DANCE
PI RESTON
PA 1900 ASSOCIATION DRIVE, RESTON, VA 22091 USA
SN 0270-1367
J9 RES Q EXERCISE SPORT
JI Res. Q. Exerc. Sport
PD JUN
PY 2010
VL 81
IS 2
BP 125
EP 126
PG 2
WC Hospitality, Leisure, Sport & Tourism; Psychology, Applied; Psychology;
Sport Sciences
SC Social Sciences - Other Topics; Psychology; Sport Sciences
GA 601RE
UT WOS:000278080200003
ER
PT J
AU Longenecker, J
Genderson, J
Dickinson, D
Malley, J
Elvevag, B
Weinberger, DR
Gold, J
AF Longenecker, Julia
Genderson, Jamie
Dickinson, Dwight
Malley, James
Elvevag, Brita
Weinberger, Daniel R.
Gold, James
TI Where have all the women gone? Participant gender in epidemiological and
non-epidemiological research of schizophrenia
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE Schizophrenia; Epidemiology; Gender
ID SEX-DIFFERENCES; PREVALENCE; DISORDER; SUICIDE; AGE
AB Though archival literature states that schizophrenia occurs equally in males and in females, recent epidemiological studies report higher incidence of schizophrenia in men than in women. Moreover, there is longstanding evidence that women may be under-represented in non-epidemiological research literature. Our first goal was to quantify gender ratios in non-epidemiological research published in 2006. Secondly, we sought to investigate which factors contribute to high numbers of men in research studies. Our final goal was to compare gender ratios in non-epidemiological schizophrenia research to reported incidence rates. In a recent metaanalysis of incidence, there were 1.4 males for each female with schizophrenia. In non-epidemiological studies of the schizophrenia patients, there was an average of 1.94 men for every woman. Although the degree to which men outnumbered women varied according to study type and region of study, research studies included more men than women across all investigated variables. Either the incidence rates are higher for men than has previously been reported or women are less visible in research settings than in the greater community. Importantly, the discrepancy between gender ratios in epidemiological and non-epidemiological research is consistent. However, specific, identifiable factors are present when male participants are greatest, suggesting that many research environments yield a higher number of men. Thus much of our understanding of the illness and its treatment is based on research conducted disproportionately with men. Published by Elsevier B.V.
C1 [Longenecker, Julia; Genderson, Jamie; Dickinson, Dwight; Elvevag, Brita; Weinberger, Daniel R.] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
[Malley, James; Gold, James] NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Gold, J (reprint author), Univ Maryland, Maryland Psychiat Res Ctr, POB 21247, Baltimore, MD 21228 USA.
EM jgold@mprc.umaryland.edu
FU National Institute of Mental Health
FX This research was supported by the National Institute of Mental Health
Intramural Research Program (NIMH IRP). The National Institute of Mental
Health Institutional Research Program ethics committee and the National
Institute of Mental Health Office of Science Policy, Planning, and
Communications (OSPPC NIMH) have reviewed and approved this manuscript.
NR 27
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U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD JUN
PY 2010
VL 119
IS 1-3
BP 240
EP 245
DI 10.1016/j.schres.2010.03.023
PG 6
WC Psychiatry
SC Psychiatry
GA 631JC
UT WOS:000280341700034
PM 20399612
ER
PT J
AU Bourboulia, D
Stetler-Stevenson, WG
AF Bourboulia, Dimitra
Stetler-Stevenson, William G.
TI Matrix metalloproteinases (MMPs) and tissue inhibitors of
metalloproteinases (TIMPs): Positive and negative regulators in tumor
cell adhesion
SO SEMINARS IN CANCER BIOLOGY
LA English
DT Review
DE Cell adhesion molecules; Extracellular matrix; Matrix
metalloproteinases; Tissue inhibitors of metalloproteinases
ID ERYTHROID-POTENTIATING ACTIVITY; BREAST-CANCER CELLS;
EXTRACELLULAR-MATRIX; BASEMENT-MEMBRANE; BETA-CATENIN; CARCINOMA-CELLS;
MOLECULAR-BASIS; IV COLLAGENASE; PROGRESSION; CADHERIN
AB Cells adhere to one another and/or to matrices that surround them. Regulation of cell-cell (intercellular) and cell-matrix adhesion is tightly controlled in normal cells, however, defects in cell adhesion are common in the majority of human cancers. Multilateral communication among tumor cells with the extracellular matrix (ECM) and neighbor cells is accomplished through adhesion molecules, ECM components, proteolytic enzymes and their endogenous inhibitors. There is sufficient evidence to suggest that reduced adherence is a tumor cell property engaged during tumor progression. Tumor cells acquire the ability to change shape, detach and easily move through spaces disorganizing the normal tissue architecture. This property is due to changes in expression levels of adhesion molecules and/or due to elevated levels of secreted proteolytic enzymes, including matrix metalloproteinases (MMPs). Among other roles, MMPs degrade the ECM and, therefore, prepare the path for tumor cells to migrate, invade and spread to distant secondary areas, where they form metastasis. Tissue inhibitors of metalloproteinases or TIMPs control MMP activities and, therefore, minimize matrix degradation. Both MMPs and TIMPs are involved in tissue remodeling and decisively regulate tumor cell progression including tumor angiogenesis. In this review, we describe and discuss data that support the important role of MMPs and TIMPs in cancer cell adhesion and tumor progression. Published by Elsevier Ltd.
C1 [Stetler-Stevenson, William G.] NCI, Extracellular Matrix Pathol Sect, Radiat Oncol Branch, Ctr Canc Res,NIH,Adv Technol Ctr, Bethesda, MD 20892 USA.
RP Stetler-Stevenson, WG (reprint author), NCI, Extracellular Matrix Pathol Sect, Radiat Oncol Branch, Ctr Canc Res,NIH,Adv Technol Ctr, 8717 Grovemont Circle, Bethesda, MD 20892 USA.
EM bourmpouliad@mail.nih.gov; sstevenw@mail.nih.gov
RI Stetler-Stevenson, William/H-6956-2012
OI Stetler-Stevenson, William/0000-0002-5500-5808
FU NCI, Center for Cancer Research [Z01SC 009179]
FX We would like to show appreciation on the work of colleagues we could
not cite due to space limitations. This work was supported by intramural
research funds from the NCI, Center for Cancer Research Project Z01SC
009179.
NR 101
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PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1044-579X
J9 SEMIN CANCER BIOL
JI Semin. Cancer Biol.
PD JUN
PY 2010
VL 20
IS 3
BP 161
EP 168
DI 10.1016/j.semcancer.2010.05.002
PG 8
WC Oncology
SC Oncology
GA 670DU
UT WOS:000283402200006
PM 20470890
ER
PT J
AU Dunn, BK
Greenwald, P
AF Dunn, Barbara K.
Greenwald, Peter
TI Cancer Prevention I: Introduction
SO SEMINARS IN ONCOLOGY
LA English
DT Editorial Material
ID SURGICAL ADJUVANT BREAST; NUTRITION INTERVENTION TRIALS; RANDOMIZED
CONTROLLED-TRIAL; DIETARY MODIFICATION TRIAL; DISEASE-SPECIFIC
MORTALITY; STOP SMOKING INTERVENTION; BOWEL PROJECT P-1; LUNG-CANCER;
SCREENING TRIAL; GENERAL-POPULATION
C1 [Greenwald, Peter] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
RP Greenwald, P (reprint author), NCI, Canc Prevent Div, NIH, 6030 Execut Blvd,Room 6020,MSC 7309, Bethesda, MD 20892 USA.
EM Peter.Greenwald@nih.hhs.gov
NR 62
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U1 0
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0093-7754
J9 SEMIN ONCOL
JI Semin. Oncol.
PD JUN
PY 2010
VL 37
IS 3
BP 190
EP 201
DI 10.1053/j.seminoncol.2010.06.011
PG 12
WC Oncology
SC Oncology
GA 640YC
UT WOS:000281089100003
PM 20709204
ER
PT J
AU Croswell, JM
Ransohoff, DF
Kramer, BS
AF Croswell, Jennifer M.
Ransohoff, David F.
Kramer, Barnett S.
TI Principles of Cancer Screening: Lessons From History and Study Design
Issues
SO SEMINARS IN ONCOLOGY
LA English
DT Review
ID CERVICAL INTRAEPITHELIAL NEOPLASIA; COMPUTED-TOMOGRAPHY SCANNER;
SERVICES-TASK-FORCE; PROSTATE-CANCER; LUNG-CANCER; COLORECTAL-CANCER;
BREAST-CANCER; FOLLOW-UP; ASYMPTOMATIC ADULTS; NEW-YORK
AB Early detection of cancer has held great promise and intuitive appeal in the medical community for well over a century. Its history developed in tandem with that of the periodic health examination, in which any deviations-subtle or glaring-from a clearly demarcated "normal" were to be rooted out, given the underlying hypothesis that diseases develop along progressive linear paths of increasing abnormalities. This model of disease development drove the logical deduction that early detection, by "breaking the chain" of cancer development, must be of benefit to affected individuals. In the latter half of the 20th century, researchers and guidelines organizations began to explicitly challenge the core assumptions underpinning many clinical practices. A move away from intuitive thinking began with the development of evidence-based medicine. One key method developed to explicitly quantify the overall risk-benefit profile of a given procedure was the analytic framework. The shift away from pure deductive reasoning and reliance on personal observation was driven, in part, by a rising awareness of critical biases in cancer screening that can mislead clinicians, including healthy volunteer bias, length-biased sampling, lead-time bias, and overdiagnosis. A new focus on the net balance of both benefits and harms when determining the overall worth of an intervention also arose: it was recognized that the potential downsides of early detection were frequently overlooked or discounted because screening is performed on basically healthy persons and initially involves relatively noninvasive methods. Although still inconsistently applied to early detection programs, policies, and belief systems in the United States, an evidence-based approach is essential to counteract the misleading-even potentially harmful-allure of intuition and individual observation. Semin Oncol 37:202-215. Published by Elsevier Inc.
C1 [Croswell, Jennifer M.] NIH, Off Med Applicat Res, Bethesda, MD 20892 USA.
[Ransohoff, David F.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA.
[Ransohoff, David F.] Univ N Carolina, Dept Epidemiol, Sch Med, Chapel Hill, NC USA.
[Ransohoff, David F.] Univ N Carolina, Dept Med, Sch Publ Hlth, Chapel Hill, NC USA.
[Ransohoff, David F.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
[Kramer, Barnett S.] NIH, Off Dis Prevent, Bethesda, MD 20892 USA.
RP Croswell, JM (reprint author), NIH, Off Med Applicat Res, 6100 Execut Blvd,Suite 2B-03, Bethesda, MD 20892 USA.
EM croswellj@od.nih.gov
FU Intramural NIH HHS [Z99 OD999999]
NR 73
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U1 1
U2 6
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0093-7754
EI 1532-8708
J9 SEMIN ONCOL
JI Semin. Oncol.
PD JUN
PY 2010
VL 37
IS 3
BP 202
EP 215
DI 10.1053/j.seminoncol.2010.05.006
PG 14
WC Oncology
SC Oncology
GA 640YC
UT WOS:000281089100004
PM 20709205
ER
PT J
AU Prorok, PC
Marcus, PM
AF Prorok, Philip C.
Marcus, Pamela M.
TI Cancer Screening Trials: Nuts and Bolts
SO SEMINARS IN ONCOLOGY
LA English
DT Review
ID FECAL OCCULT BLOOD; BASE-LINE FINDINGS; BREAST-CANCER;
COLORECTAL-CANCER; LUNG-CANCER; FLEXIBLE SIGMOIDOSCOPY; RANDOMIZED
FEASIBILITY; PREVENTION TRIALS; SPIRAL CT; MORTALITY
AB The most rigorous and valid approach to evaluating cancer screening modalities is the randomized controlled trial (RCT). RCTs are major undertakings and the intricacies of trial design, operations, and management are generally underappreciated by the typical researcher. The purpose of this article is to inform the reader of the "nuts and bolts" of designing and conducting cancer screening RCTs. Following a brief introduction as to why RCTs are critical in evaluating screening modalities, we discuss design considerations, including the choice of design type and duration of follow-up. We next present an approach to sample-size calculations. We then discuss aspects of trial implementation, including recruitment, randomization, and data management. A discussion of commonly employed data analyses comes next, and includes methods for the primary analysis (comparison of cause-specific mortality rates between the screened and control arms for the cancer of interest), as well as for secondary endpoints such as sensitivity. We follow with a discussion of sequential monitoring and interim analysis techniques, which are used to examine the primary outcome while the trial is ongoing. We close with thoughts on lessons learned from past cancer screening RCTs and provide recommendations for future trials. Throughout the presentation we illustrate topics with examples from completed or ongoing RCTs, including the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and the National Lung Screening Trial (NLST). Semin Oncol 37:216-223. (C) 2010 Published by Elsevier Inc.
C1 [Prorok, Philip C.] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
RP Prorok, PC (reprint author), NCI, Canc Prevent Div, NIH, 6130 Execut Blvd,EPN Room 3132, Bethesda, MD 20892 USA.
EM pp2g@nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 59
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Z9 4
U1 0
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0093-7754
J9 SEMIN ONCOL
JI Semin. Oncol.
PD JUN
PY 2010
VL 37
IS 3
BP 216
EP 223
DI 10.1053/j.seminoncol.2010.05.009
PG 8
WC Oncology
SC Oncology
GA 640YC
UT WOS:000281089100005
PM 20709206
ER
PT J
AU Dunn, BK
Wagner, PD
Anderson, D
Greenwald, P
AF Dunn, Barbara K.
Wagner, Paul D.
Anderson, Darrell
Greenwald, Peter
TI Molecular Markers for Early Detection
SO SEMINARS IN ONCOLOGY
LA English
DT Review
ID METASTATIC PROSTATE-CANCER; HEPATOCELLULAR-CARCINOMA; BREAST-CANCER;
LUNG-CANCER; COLORECTAL-CANCER; PANCREATIC-CANCER; OVARIAN-CANCER;
PROMOTER HYPERMETHYLATION; BLADDER-CANCER; MULTIPLE GENES
AB A common belief is that the earlier that cancer is detected, the better the chance exists for reduced mortality and morbidity. The advent of new and emerging molecular, genetic, and imaging technologies has broadened the possible strategies for early detection and prevention, but a beneficial impact on mortality needs to be supported by clinical evidence. Molecular markers are being identified that are enhancing our ability to predict and detect cancer before it develops and at the earliest signs of impending carcinogenic transformation. Of the innumerable molecular markers in development, a standalone early detection marker with acceptable sensitivity and specificity is available for bladder cancer, although for most cancer sites there are promising avenues of research that will likely produce results in the next decade. The perfect molecular marker would be one that is inherently related to the disease, specifically to the processes of malignant tumorigenesis or to the defense mechanisms of the individual. For example, mutations associated with increased cancer risk often produce gene products that interfere with tumor-suppressor pathways (eg, DNA repair or cell-cycle control) or support oncogenic pathways (eg, through genetic instability or silencing the apoptotic pathway). Finding molecular markers associated with these processes, and where in the process they produce their actions, can lead to interventions based on maintaining support for the normal process and interrupting the action of the products of the mutation. The search for molecular markers for cancer prevention and early detection presents a formidable challenge that requires a systematic and scientifically sound validation process. The search encompasses a broad range of scientific disciplines, including biochemistry, genetics, histology, immunology, informatic technologies, and epidemiology; strategies to identify and understand molecular markers are approached with multidisciplinary teams focused on understanding the mechanistic basis of cancer and the processes and pathways that underlie carcinogenesis. Semin Oncol 37:224-242. (C) 2010 Published by Elsevier Inc.
C1 [Dunn, Barbara K.; Wagner, Paul D.; Greenwald, Peter] NCI, Basic Prevent Sci Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
[Anderson, Darrell] Sci Consulting Grp, Gaithersburg, MD USA.
RP Dunn, BK (reprint author), NCI, Basic Prevent Sci Res Grp, Canc Prevent Div, 6130 Execut Blvd,Room 2056, Bethesda, MD 20892 USA.
EM dunnb@mail.nih.gov
NR 87
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U1 1
U2 9
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0093-7754
J9 SEMIN ONCOL
JI Semin. Oncol.
PD JUN
PY 2010
VL 37
IS 3
BP 224
EP 242
DI 10.1053/j.seminoncol.2010.05.007
PG 19
WC Oncology
SC Oncology
GA 640YC
UT WOS:000281089100006
PM 20709207
ER
PT J
AU Davis, CD
Emenaker, NJ
Milner, JA
AF Davis, Cindy D.
Emenaker, Nancy J.
Milner, John A.
TI Cellular Proliferation, Apoptosis and Angiogenesis: Molecular Targets
for Nutritional Preemption of Cancer
SO SEMINARS IN ONCOLOGY
LA English
DT Review
ID ENDOTHELIAL GROWTH-FACTOR; HUMAN PROSTATE-CANCER; GREEN TEA POLYPHENOL;
RESVERATROL-INDUCED APOPTOSIS; HUMAN TUMOR-CELLS; FACTOR-KAPPA-B; CYCLE
ARREST; IN-VITRO; EPIGALLOCATECHIN GALLATE; PANCREATIC-CANCER
AB Malignant cells are characterized by abnormal signaling pathways involving proliferation, apoptosis, and angiogenesis. These cancer centric pathways are known to be modified by several bioactive dietary components, although admittedly there are inconsistencies in the response. The response is dependent on the amount and duration of exposure to the dietary component and the cell type. While caution should be exercised when extrapolating in vitro data to in vivo conditions, such studies do provide valuable insights into plausible mechanisms. Significant gene-nutrient and nutrient-nutrient interactions may contribute to the uncertainty of the response to foods and/or their components. One of the challenges is the identification of which process(es), either singly or in combination, is/are most important in leading to a dietary-mediated phenotypic change. The dearth of controlled intervention studies that have investigated molecular targets for nutritional preemption in humans make firm dietary recommendations difficult. Until more definite information surfaces, a balanced but varied diet is most prudent. Semin Oncol 37:243-257. Published by Elsevier Inc.
C1 [Davis, Cindy D.; Emenaker, Nancy J.; Milner, John A.] NCI, Nutr Sci Res Grp, Canc Prevent Div, Rockville, MD 20892 USA.
RP Davis, CD (reprint author), NCI, Nutr Sci Res Grp, Canc Prevent Div, 6130 Execut Blvd,Suite 3159, Rockville, MD 20892 USA.
EM davisci@mail.nih.gov
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U1 0
U2 8
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0093-7754
J9 SEMIN ONCOL
JI Semin. Oncol.
PD JUN
PY 2010
VL 37
IS 3
BP 243
EP 257
DI 10.1053/j.seminoncol.2010.05.001
PG 15
WC Oncology
SC Oncology
GA 640YC
UT WOS:000281089100007
PM 20709208
ER
PT J
AU Gibson, TM
Ferrucci, LM
Tangrea, JA
Schatzkin, A
AF Gibson, Todd M.
Ferrucci, Leah M.
Tangrea, Joseph A.
Schatzkin, Arthur
TI Epidemiological and Clinical Studies of Nutrition
SO SEMINARS IN ONCOLOGY
LA English
DT Review
ID COLORECTAL-CANCER RISK; NIH-AARP DIET; RANDOMIZED CONTROLLED-TRIAL; FOOD
FREQUENCY QUESTIONNAIRE; BETA-CAROTENE SUPPLEMENTATION; POSTMENOPAUSAL
BREAST-CANCER; HETEROCYCLIC AMINE CONTENT; LONG-TERM SUPPLEMENTATION;
LARGE PROSPECTIVE COHORT; HIGH-FIBER DIET
AB In this review, we briefly summarize some of the key developments in nutritional epidemiology and cancer over the past two decades with a focus on the strengths and limitations of study designs and dietary assessment methods. We present the evidence on dietary fat, meat, fiber, antioxidant nutrients, and calcium in relation to carcinogenesis from large cohort studies and randomized clinical trials (RCTs) and refer to the conclusions of the 2007 World Cancer Research Fund/American Institute for Cancer Research summary report. One prominent theme that emerged is the lack of concordance of results from RCTs and observational studies. There are multiple potential reasons for these discrepancies, including differences in study population, dose and timing of the exposure, adherence to an intervention, length of follow-up, and the primary endpoint. Therefore, null findings of RCTs do not necessarily indicate a lack of effect for the tested dietary factors on cancer risk, as some of these nutrients may have chemopreventive effects if given at the right time and in the right dose. It is likely that potential benefits from diet are due to a combination of food constituents rather than single components acting in isolation. Future efforts need to recognize the integrative nature of dietary exposures and attempt to study nutrients in the larger context of the foods and diets in which they are consumed. Semin Oncol 37:282-296. Published by Elsevier Inc.
C1 [Gibson, Todd M.; Schatzkin, Arthur] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA.
[Gibson, Todd M.] Yale Univ, Sch Publ Hlth, New Haven, CT USA.
[Ferrucci, Leah M.] Yale Univ, Sch Nursing, New Haven, CT 06536 USA.
[Tangrea, Joseph A.] NCI, Canc Prevent Div, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA.
RP Gibson, TM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd, Rockville, MD 20852 USA.
EM gibsontm@mail.nih.gov
FU National Institutes of Health; National Cancer Institute;
[TU2-CA-105666]
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health and the National Cancer Institute
and by grant no. TU2-CA-105666.
NR 172
TC 19
Z9 20
U1 1
U2 9
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0093-7754
J9 SEMIN ONCOL
JI Semin. Oncol.
PD JUN
PY 2010
VL 37
IS 3
BP 282
EP 296
DI 10.1053/j.seminoncol.2010.05.011
PG 15
WC Oncology
SC Oncology
GA 640YC
UT WOS:000281089100009
PM 20709210
ER
PT J
AU Kreimer, AR
Bhatia, RK
Messeguer, AL
Gonzalez, P
Herrero, R
Giuliano, AR
AF Kreimer, Aimee R.
Bhatia, Rohini K.
Messeguer, Andrea L.
Gonzalez, Paula
Herrero, Rolando
Giuliano, Anna R.
TI Oral Human Papillomavirus in Healthy Individuals: A Systematic Review of
the Literature
SO SEXUALLY TRANSMITTED DISEASES
LA English
DT Review
ID HUMAN-IMMUNODEFICIENCY-VIRUS; NATURAL-HISTORY; RISK-FACTORS; PREVALENCE;
POPULATION; INFECTION; WOMEN; METAANALYSIS; MUCOSA; CANCER
AB Background: Human papillomavirus type 16 (HPV16) is a common infection in the anogenital tract. HPV16 DNA detected in oral specimens has recently been identified as a risk factor for some oropharyngeal cancers. The reported prevalence of oral HPV infection from individual studies is highly variable.
Methods: We systematically reviewed and abstracted data from published studies (n = 18) that detected oral HPV DNA in 4581 cancer-free subjects to determine the pooled prevalence (and 95% confidence intervals [CI]) of HPV16, carcinogenic HPV, and any HPV.
Results: 1.3% (95% CI: 1.0-1.7%) of 3977 healthy subjects had oral HPV16, 3.5% (95% CI: 3.0-4.1) of 4441 subjects had carcinogenic HPV, and 4.5% (95% CI: 3.9-5.1) of 4070 subjects were positive for any HPV. Oral HPV16 accounted for 28% of all HPV detected in the oral region. Men (47 of 1017) and women (117 of 3690) had nearly exactly the same prevalence of any oral HPV detected (4.6% vs. 4.4%, respectively).
Conclusions: HPV-16, a common anogenital infection, was rarely detected in oral specimens. However, a small but noteworthy proportion of healthy individuals have oral HPV infections with types known to cause cancer in the oral region.
C1 [Kreimer, Aimee R.; Bhatia, Rohini K.] NCI, NIH, Bethesda, MD 20892 USA.
[Messeguer, Andrea L.; Gonzalez, Paula; Herrero, Rolando] Fdn INCIENSA, San Jose, Costa Rica.
[Giuliano, Anna R.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA.
RP Kreimer, AR (reprint author), 6120 Execut Blvd,EPS 7084, Rockville, MD 20852 USA.
EM kreimera@mail.nih.gov
RI Kreimer, Aimee/H-1687-2015
NR 33
TC 111
Z9 114
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0148-5717
J9 SEX TRANSM DIS
JI Sex. Transm. Dis.
PD JUN
PY 2010
VL 37
IS 6
BP 386
EP 391
DI 10.1097/OLQ.0b013e3181c94a3b
PG 6
WC Infectious Diseases
SC Infectious Diseases
GA 605WT
UT WOS:000278379700010
PM 20081557
ER
PT J
AU Vong, QP
Liu, ZH
Yoo, JG
Chen, R
Xie, W
Sharov, AA
Fan, CM
Liu, CY
Ko, MSH
Zheng, YX
AF Vong, Queenie P.
Liu, Zhonghua
Yoo, Jae Gyu
Chen, Rong
Xie, Wen
Sharov, Alexei A.
Fan, Chen-Ming
Liu, Chengyu
Ko, Minoru S. H.
Zheng, Yixian
TI A Role for Borg5 During Trophectoderm Differentiation
SO STEM CELLS
LA English
DT Article
DE Borg5; Cdx2; Embryonic stem cells; Trophectoderm; Cell morphogenesis;
Transcription; Differentiation
ID EMBRYONIC STEM-CELLS; MOUSE BLASTOCYST; RNA INTERFERENCE; SELF-RENEWAL;
EXPRESSION; CDX2; PLURIPOTENCY; LINEAGE; NANOG; MASS
AB Stem cell differentiation is accompanied by a gradual cellular morphogenesis and transcriptional changes. Identification of morphological regulators that control cell behavior during differentiation could shed light on how cell morphogenesis is coupled to transcriptional changes during development. By analyzing cellular behavior during differentiation of mouse embryonic stem cells (ESCs), we uncover a role of Borg5 (binder of Rho guanosine 5'-triphosphatase 5) in regulating trophectoderm (TE) cell morphogenesis. We report that differentiation of ESCs toward TE is accompanied by enhanced actin protrusion and cell motility that require upregulation of Borg5. Borg5 interacts with both Cdc42 and atypical protein kinase C (aPKC) and functions downstream of Cdc42 to enhance TE cell motility. Borg5 is required for the sorting of differentiating TE to the outside of ESCs in vitro. In developing embryos, Borg5 protein localizes to cell cell contacts and the cytoplasm after compaction. It exhibits higher levels of expression in outer cells than in inner cells in morula and blastocysts. Reduction of Borg5 disrupts aPKC localization and inhibits blastocyst formation. Since Cdx2 and Borg5 facilitate each other's expression as ESCs differentiate toward TE, we propose that cell morphogenesis is coupled with transcriptional changes to regulate TE differentiation. Our studies also demonstrate the utility of ESCs in identifying morphological regulators important for development. STEM CELLS 2010;28:1030-1038
C1 [Zheng, Yixian] Howard Hughes Med Inst, Carnegie Inst Sci, Dept Embryol, Baltimore, MD 21218 USA.
[Yoo, Jae Gyu; Sharov, Alexei A.; Ko, Minoru S. H.] NIA, Dev Genom & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA.
[Xie, Wen; Liu, Chengyu] NHLBI, Transgen Core Facil, NIH, Bethesda, MD 20892 USA.
RP Zheng, YX (reprint author), Howard Hughes Med Inst, Carnegie Inst Sci, Dept Embryol, Baltimore, MD 21218 USA.
EM zheng@ciwemb.edu
RI Ko, Minoru/B-7969-2009
OI Ko, Minoru/0000-0002-3530-3015
FU NIH
FX We thank Drs. Hitoshi Niwa, Janet Rossant, and Austin Smith for the
ZHBTc4 cells, the TS cells, and the pCAG-IP vector, respectively, Ona
Martin for technical support, and the members of the Zheng laboratory
for critical comments. This work was supported by the Intramural
Research Program of the NIH (NIA: J.G.Y., A.S., and M. K.; NHLBI: C.L.).
Y.Z. is an investigator of HHMI. Q.P.V. and Z.L. contributed equally to
this article. J.G.Y. is currently affiliated with the Animal
Biotechnology Division, National Institute of Animal Science, Rural
Development Administration, 250 Omokcheon-Dong, Gwonseon-Gu Suwon
441-350, Republic of Korea.
NR 27
TC 12
Z9 12
U1 0
U2 2
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1066-5099
J9 STEM CELLS
JI Stem Cells
PD JUN
PY 2010
VL 28
IS 6
BP 1030
EP 1038
DI 10.1002/stem.428
PG 9
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA 615AQ
UT WOS:000279103500004
PM 20506138
ER
PT J
AU Hachinski, V
Donnan, GA
Gorelick, PB
Hacke, W
Cramer, SC
Kaste, M
Fisher, M
Brainin, M
Buchan, AM
Lo, EH
Skolnick, BE
Furie, KL
Hankey, GJ
Kivipelto, M
Morris, J
Rothwell, PM
Sacco, RL
Smith, SC
Wang, YL
Bryer, A
Ford, GA
Iadecola, C
Martins, SCO
Saver, J
Skvortsova, V
Bayley, M
Bednar, MM
Duncan, P
Enney, L
Finklestein, S
Jones, TA
Kalra, L
Kleim, J
Nitkin, R
Teasell, R
Weiller, C
Desai, B
Goldberg, MP
Heiss, WD
Saarelma, O
Schwamm, LH
Shinohara, Y
Trivedi, B
Wahlgren, N
Wong, LK
Hakim, A
Norrving, B
Prudhomme, S
Bornstein, NM
Davis, SM
Goldstein, LB
Leys, D
Tuomilehto, J
AF Hachinski, Vladimir
Donnan, Geoffrey A.
Gorelick, Philip B.
Hacke, Werner
Cramer, Steven C.
Kaste, Markku
Fisher, Marc
Brainin, Michael
Buchan, Alastair M.
Lo, Eng H.
Skolnick, Brett E.
Furie, Karen L.
Hankey, Graeme J.
Kivipelto, Miia
Morris, John
Rothwell, Peter M.
Sacco, Ralph L.
Smith, Sidney C., Jr.
Wang, Yulun
Bryer, Alan
Ford, Gary A.
Iadecola, Costantino
Martins, Sheila C. O.
Saver, Jeff
Skvortsova, Veronika
Bayley, Mark
Bednar, Martin M.
Duncan, Pamela
Enney, Lori
Finklestein, Seth
Jones, Theresa A.
Kalra, Lalit
Kleim, Jeff
Nitkin, Ralph
Teasell, Robert
Weiller, Cornelius
Desai, Bhupat
Goldberg, Mark P.
Heiss, Wolf-Dieter
Saarelma, Osmo
Schwamm, Lee H.
Shinohara, Yukito
Trivedi, Bhargava
Wahlgren, Nils
Wong, Lawrence K.
Hakim, Antoine
Norrving, Bo
Prudhomme, Stephen
Bornstein, Natan M.
Davis, Stephen M.
Goldstein, Larry B.
Leys, Didier
Tuomilehto, Jaakko
TI Stroke: Working Toward a Prioritized World Agenda
SO STROKE
LA English
DT Article
DE prevention; rehabilitation; stroke; translational; treatment
ID VASCULAR COGNITIVE IMPAIRMENT; TISSUE-PLASMINOGEN ACTIVATOR; TRANSIENT
ISCHEMIC ATTACK; HEALTHY LIFE-STYLE; PRIMARY PREVENTION; POLICY
STATEMENT; CARE; RECOMMENDATIONS; PROGRESS; BRAIN
AB Background and Purpose-The aim of the Synergium was to devise and prioritize new ways of accelerating progress in reducing the risks, effects, and consequences of stroke.
Methods-Preliminary work was performed by 7 working groups of stroke leaders followed by a synergium (a forum for working synergistically together) with approximately 100 additional participants. The resulting draft document had further input from contributors outside the synergium.
Results-Recommendations of the Synergium are:
Basic Science, Drug Development and Technology: There is a need to develop: (1) New systems of working together to break down the prevalent "silo" mentality; (2) New models of vertically integrated basic, clinical, and epidemiological disciplines; and (3) Efficient methods of identifying other relevant areas of science.
Stroke Prevention: (1) Establish a global chronic disease prevention initiative with stroke as a major focus. (2) Recognize not only abrupt clinical stroke, but subtle subclinical stroke, the commonest type of cerebrovascular disease, leading to impairments of executive function. (3) Develop, implement and evaluate a population approach for stroke prevention. (4) Develop public health communication strategies using traditional and novel (eg, social media/marketing) techniques.
Acute Stroke Management: Continue the establishment of stroke centers, stroke units, regional systems of emergency stroke care and telestroke networks.
Brain Recovery and Rehabilitation: (1) Translate best neuroscience, including animal and human studies, into poststroke recovery research and clinical care. (2) Standardize poststroke rehabilitation based on best evidence. (3) Develop consensus on, then implementation of, standardized clinical and surrogate assessments. (4) Carry out rigorous clinical research to advance stroke recovery.
Into the 21st Century: Web, Technology and Communications: (1) Work toward global unrestricted access to stroke-related information. (2) Build centralized electronic archives and registries.
Foster Cooperation Among Stakeholders (large stroke organizations, nongovernmental organizations, governments, patient organizations and industry) to enhance stroke care.
Educate and energize professionals, patients, the public and policy makers by using a "Brain Health" concept that enables promotion of preventive measures.
Conclusions-To accelerate progress in stroke, we must reach beyond the current status scientifically, conceptually, and pragmatically. Advances can be made not only by doing, but ceasing to do. Significant savings in time, money, and effort could result from discontinuing practices driven by unsubstantiated opinion, unproven approaches, and financial gain. Systematic integration of knowledge into programs coupled with careful evaluation can speed the pace of progress.
C1 [Hachinski, Vladimir] Univ Western Ontario, Dept Clin Neurol Sci, London Hlth Sci Ctr, London, ON N6A 5A5, Canada.
[Donnan, Geoffrey A.] Florey Neurosci Inst, Carlton, Vic, Australia.
[Gorelick, Philip B.] Univ Illinois, Chicago, IL USA.
[Hacke, Werner] Univ Heidelberg, Heidelberg, Germany.
[Cramer, Steven C.] Univ Calif Irvine, Orange, CA 92668 USA.
[Kaste, Markku] Univ Helsinki, Helsinki Univ Cent Hosp, Helsinki, Finland.
[Fisher, Marc] Univ Massachusetts, Sch Med, Worcester, MA USA.
[Brainin, Michael] Univ Donau Univ Krems, Krems, Austria.
[Buchan, Alastair M.] Univ Oxford, Oxford, England.
[Lo, Eng H.; Furie, Karen L.; Schwamm, Lee H.] Massachusetts Gen Hosp, Charlestown, MA USA.
[Skolnick, Brett E.] Novo Nordisk, Princeton, NJ USA.
[Hankey, Graeme J.] Royal Perth Hosp, Perth, WA, Australia.
[Kivipelto, Miia; Wahlgren, Nils] Karolinska Inst, Stockholm, Sweden.
[Morris, John; Goldberg, Mark P.] Washington Univ, Sch Med, St Louis, MO USA.
[Rothwell, Peter M.] John Radcliffe Hosp, Oxford OX3 9DU, England.
[Sacco, Ralph L.] Univ Miami, AHA, Miami, FL USA.
[Smith, Sidney C., Jr.] Univ N Carolina, Ctr Cardiovasc Sci & Med, Chapel Hill, NC USA.
World Heart Federat, Geneva, Switzerland.
[Wang, Yulun] InTouch Hlth, Goleta, CA USA.
[Bryer, Alan] Groote Schuur Hosp, ZA-7925 Cape Town, South Africa.
[Bryer, Alan] Univ Cape Town, ZA-7925 Cape Town, South Africa.
[Ford, Gary A.] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Iadecola, Costantino] Weill Cornell Med Coll, New York, NY USA.
[Martins, Sheila C. O.] Hosp Clin, Porto Alegre, RS, Brazil.
[Saver, Jeff] Univ Calif Los Angeles, Los Angeles Stroke Ctr, Los Angeles, CA USA.
[Skvortsova, Veronika] Russian State Res Stroke Inst, Moscow, Russia.
[Bayley, Mark] Toronto Rehabil Inst, Toronto, ON, Canada.
[Bednar, Martin M.] Pfizer Inc, Neurosci Res Unit, Groton, CT 06340 USA.
[Duncan, Pamela; Goldstein, Larry B.] Duke Univ, Durham, NC USA.
[Enney, Lori] GlaxoSmithKline Inc, Durham, NC USA.
[Finklestein, Seth] Biotrofix Inc, Waltham, MA USA.
[Jones, Theresa A.] Univ Texas Austin, Austin, TX 78712 USA.
[Kalra, Lalit] Kings Coll London, London WC2R 2LS, England.
[Kleim, Jeff] Univ Florida, Gainesville, FL USA.
[Nitkin, Ralph] NICHHD, Natl Ctr Med Rehabil, NIH, Rockville, MD USA.
[Teasell, Robert] St Josephs Healthcare London, London, ON, Canada.
[Weiller, Cornelius] Univ Freiburg, Freiburg, Germany.
[Desai, Bhupat] Pomona Valley Hosp Med Ctr, Pomona, CA USA.
[Heiss, Wolf-Dieter] Max Planck Inst Neurol Res, Cologne, Germany.
[Saarelma, Osmo] Terveystalo Med Ctr, Helsinki, Finland.
[Shinohara, Yukito] Tachikawa Hosp, Tokyo, Japan.
[Trivedi, Bhargava] So Illinois Healthcare, Carbondale, IL USA.
[Wong, Lawrence K.] Chinese Univ Hong Kong, Sha Tin, Hong Kong, Peoples R China.
[Hakim, Antoine] Univ Ottawa, Canadian Stroke Network, Ottawa, ON, Canada.
Ottawa Hosp Res Inst, Ottawa, ON, Canada.
[Norrving, Bo] Univ Lund Hosp, S-22185 Lund, Sweden.
[Prudhomme, Stephen] Amer Heart Assoc, Dallas, TX USA.
[Bornstein, Natan M.] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, IL-69978 Tel Aviv, Israel.
[Davis, Stephen M.] Royal Melbourne Hosp, Melbourne, Vic, Australia.
Univ Melbourne, Melbourne, Vic, Australia.
[Goldstein, Larry B.] Durham VA Med Ctr, Durham, NC USA.
[Leys, Didier] Univ Lille Nord France, Lille, France.
[Tuomilehto, Jaakko] Univ Helsinki, Helsinki, Finland.
RP Hachinski, V (reprint author), Univ Western Ontario, Univ Hosp, 339 Windermere Rd, London, ON N6A 5A5, Canada.
EM Vladimir.Hachinski@lhsc.on.ca
RI Skolnick, Brett/B-5140-2009; Buchan, Alastair/B-9095-2009; Jones,
Theresa/F-1182-2010; Davis, Stephen/L-5260-2013; Wong, Ka Sing
Lawrence/N-3434-2015; LEYS, Didier/G-2955-2016;
OI Saver, Jeffrey/0000-0001-9141-2251; Kaste, Markku/0000-0001-6557-6412;
Buchan, Alastair/0000-0002-2918-5200; Jones,
Theresa/0000-0003-0906-6439; Davis, Stephen/0000-0003-0962-2300; Wong,
Ka Sing Lawrence/0000-0002-2031-9866; LEYS, Didier/0000-0003-4408-4392;
Kivipelto, Miia/0000-0003-0992-3875; Norrving, Bo/0000-0002-8024-5096;
Schwamm, Lee/0000-0003-0592-9145; Donnan, Geoffrey/0000-0001-6324-3403
FU Medical Research Council [G0500495]; NINDS NIH HHS [P01 NS055104, RC2
NS069335]
NR 83
TC 54
Z9 55
U1 2
U2 16
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD JUN
PY 2010
VL 41
IS 6
BP 1084
EP 1099
DI 10.1161/STROKEAHA.110.586156
PG 16
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 600WK
UT WOS:000278019400006
PM 20498453
ER
PT J
AU Deka, R
Koller, DL
Lai, DB
Indugula, SR
Sun, GY
Woo, D
Sauerbeck, L
Moomaw, CJ
Hornung, R
Connolly, ES
Anderson, C
Rouleau, G
Meissner, I
Bailey-Wilson, JE
Huston, J
Brown, RD
Kleindorfer, DO
Flaherty, ML
Langefeld, CD
Foroud, T
Broderick, JP
AF Deka, Ranjan
Koller, Daniel L.
Lai, Dongbing
Indugula, Subba Rao
Sun, Guangyun
Woo, Daniel
Sauerbeck, Laura
Moomaw, Charles J.
Hornung, Richard
Connolly, E. Sander
Anderson, Craig
Rouleau, Guy
Meissner, Irene
Bailey-Wilson, Joan E.
Huston, John, III
Brown, Robert D.
Kleindorfer, Dawn O.
Flaherty, Matthew L.
Langefeld, Carl D.
Foroud, Tatiana
Broderick, Joseph P.
CA FIA Study Investigators
TI The Relationship Between Smoking and Replicated Sequence Variants on
Chromosomes 8 and 9 With Familial Intracranial Aneurysm
SO STROKE
LA English
DT Article
DE familial; genomewide association studies; intracranial aneurysm; smoking
ID GENOME-WIDE ASSOCIATION; CORONARY-ARTERY-DISEASE; SUBARACHNOID
HEMORRHAGE; RISK-FACTORS; SUSCEPTIBILITY; LOCI; ALCOHOL; LINKAGE; SCREEN
AB Background and Purpose-The purpose of this study was to replicate the previous association of single nucleotide polymorphisms (SNPs) with risk of intracranial aneurysm (IA) and to examine the relationship of smoking with these variants and the risk of IA.
Methods-White probands with an IA from families with multiple affected members were identified by 26 clinical centers located throughout North America, New Zealand, and Australia. White control subjects free of stroke and IA were selected by random digit dialing from the Greater Cincinnati population. SNPs previously associated with IA on chromosomes 2, 8, and 9 were genotyped using a TaqMan assay or were included in the Affymetrix 6.0 array that was part of a genomewide association study of 406 IA cases and 392 control subjects. Logistic regression modeling tested whether the association of replicated SNPs with IA was modulated by smoking.
Results-The strongest evidence of association with IA was found with the 8q SNP rs10958409 (genotypic P = 9.2 x 10(-5); allelic P = 1.3 x 10(-5); OR = 1.86, 95% CI: 1.40 to 2.47). We also replicated the association with both SNPs on chromosome 9p, rs1333040 and rs10757278, but were not able to replicate the previously reported association of the 2 SNPs on chromosome 2q. Statistical testing showed a multiplicative relationship between the risk alleles and smoking with regard to the risk of IA.
Conclusion-Our data provide complementary evidence that the variants on chromosomes 8q and 9p are associated with IA and that the risk of IA in patients with these variants is greatly increased with cigarette smoking. (Stroke. 2010; 41: 1132-1137.)
C1 [Broderick, Joseph P.] Univ Cincinnati, Acad Hlth Ctr, Dept Neurol, UC Neurosci Inst,Coll Med, Cincinnati, OH 45267 USA.
[Lai, Dongbing; Foroud, Tatiana] Indiana Univ, Sch Med, Indianapolis, IN USA.
[Meissner, Irene; Huston, John, III; Brown, Robert D.] Mayo Clin, Rochester, MN USA.
[Hornung, Richard] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA.
[Anderson, Craig] Univ Sydney, George Inst Int Hlth, Sydney, NSW 2006, Australia.
[Rouleau, Guy] Univ Montreal, Notre Dame Hosp, Montreal, PQ H3C 3J7, Canada.
[Connolly, E. Sander] Columbia Univ, New York, NY USA.
[Langefeld, Carl D.] Wake Forest Univ Med, Winston Salem, NC USA.
[Bailey-Wilson, Joan E.] NHGRI, NIH, Baltimore, MD USA.
RP Broderick, JP (reprint author), Univ Cincinnati, Acad Hlth Ctr, Dept Neurol, UC Neurosci Inst,Coll Med, 260 Stetson St,Suite 2300,POB 670525, Cincinnati, OH 45267 USA.
EM joseph.broderick@uc.edu
OI Bailey-Wilson, Joan/0000-0002-9153-2920
FU National Institute of Neurological Diseases and Stroke (NINDS) [R01
NS39512, R-01-NS 36695]; National Institutes of Health, Bethesda, Md;
State of Ohio [TECH 04-042]; Ohio Department of Development; Wright
Centers of Innovation Program Computational Medicine Center; National
Institutes of Health, National Cancer Institutem and National Human
Genome Research Institute
FX This study was funded by grants from the National Institute of
Neurological Diseases and Stroke (NINDS R01 NS39512; R-01-NS 36695),
National Institutes of Health, Bethesda, Md; the State of Ohio TECH
04-042, Ohio Department of Development, Wright Centers of Innovation
Program Computational Medicine Center for the "Cincinnati Control Cohort
Study"; and by the Intramural Research Program of the National
Institutes of Health, National Cancer Institutem and National Human
Genome Research Institute.
NR 22
TC 24
Z9 26
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD JUN
PY 2010
VL 41
IS 6
BP 1132
EP 1137
DI 10.1161/STROKEAHA.109.574640
PG 6
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 600WK
UT WOS:000278019400012
PM 20190001
ER
PT J
AU Sojkova, J
Najjar, SS
Beason-Held, LL
Metter, EJ
Kraut, MA
Zonderman, AB
Resnick, SM
AF Sojkova, Jitka
Najjar, Samer S.
Beason-Held, Lori L.
Metter, E. Jeffrey
Kraut, Michael A.
Zonderman, Alan B.
Resnick, Susan M.
TI Subclinical Cerebrovascular Disease in Older Adults Response
SO STROKE
LA English
DT Letter
ID INTIMA-MEDIA THICKNESS; POPULATION
C1 [Sojkova, Jitka; Najjar, Samer S.; Beason-Held, Lori L.; Metter, E. Jeffrey; Zonderman, Alan B.; Resnick, Susan M.] NIA, NIH, Baltimore, MD 21224 USA.
[Sojkova, Jitka; Kraut, Michael A.] Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, Sch Med, Baltimore, MD USA.
RP Sojkova, J (reprint author), NIA, NIH, Baltimore, MD 21224 USA.
NR 9
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD JUN
PY 2010
VL 41
IS 6
BP E448
EP E449
DI 10.1161/STROKEAHA.110.583690
PG 2
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 600WK
UT WOS:000278019400046
ER
PT J
AU Weinreich, J
Agren, MS
Bilali, E
Kleinman, HK
Coerper, S
Konigsrainer, A
Beckert, S
AF Weinreich, Juergen
Agren, Magnus S.
Bilali, Erol
Kleinman, Hynda K.
Coerper, Stephan
Koenigsrainer, Alfred
Beckert, Stefan
TI Effects of isoniazid and niacin on experimental wound-healing
SO SURGERY
LA English
DT Article
ID NICOTINIC-ACID; LEG ULCERS; IDENTIFICATION; RELEASE; INHIBITION;
EXPRESSION; DRESSINGS; GROWTH; RATS; CARE
AB Background. There is a need for effective treatments of ischemic wounds. Our aim was to test the hypothesis that systemic administration of isoniazid or niacin can enhance wound healing in ischemic as well as nonischemic tissues.
Methods. One 8-mm, full-thickness wound was made in a standardized, ischemic skin flap and 1 in adjacent nonischemic skin on the back of male Sprague-Dawley rats. Starting just after wounding, twice-daily intraperitoneal isoniazid (10 mg/kg b.i.d.), xanthinol nicotinate (30 mg/kg), or saline (control) were given for 14 days. Wound-healing was monitored by planimetry and oxygen tension in periphery of the wound using a microcatheter probe. Cellular proliferation in granulation tissue was assessed by immunohistochemical detection of proliferating cell nuclear antigen. The angiogenic activity of isoniazid and niacin was assessed using in vitro and ex vivo models.
Results. Although wound ischemia was evident by decreased oxygen, tension (26 +/- 10 mmHg; n = 9) compared with the adjacent non ischemic wounds (51 +/- 8 mmHg; n = 8), neither compound significantly influenced intracutaneous oxygen tension. Isoniazid (P < .0001), but not niacin, promoted ischemic wound-healing even though both compounds increased proliferation measured on day 14 (P < .01). In normal wounds, the cumulative change in relative wound area over 14 days was increased by niacin (P = .002), but not by isoniazid, although both niacin (P = .011) and isoniazid (P = .036) increased cellular proliferation. Neither isoniazid nor niacin showed activity in either an endothelial tube formation assay or organotypic angiogenic assay under normoxic conditions.
Conclusion. Isoniazid was capable of stimulating wound-healing in ischemic tissue to the level of nonischemic wounds and might offer a novel treatment option for wounds associated with arterial in insufficiency. Although active in normal wounds, niacin did not promote ischemic wound-healing. (Surgery 2010;147:780-8.)
C1 [Weinreich, Juergen; Bilali, Erol; Coerper, Stephan; Koenigsrainer, Alfred; Beckert, Stefan] Univ Tubingen Hosp, Dept Gen & Transplant Surg, DE-72076 Tubingen, Germany.
[Agren, Magnus S.] Bispebjerg Hosp, Dept Surg K, DK-2400 Copenhagen, Denmark.
[Kleinman, Hynda K.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
[Agren, Magnus S.] Bispebjerg Hosp, Copenhagen Wound Healing Ctr, DK-2400 Copenhagen, Denmark.
RP Beckert, S (reprint author), Univ Tubingen Hosp, Dept Gen & Transplant Surg, Hoppe Seyler Str 3, DE-72076 Tubingen, Germany.
EM stefan.beckert@med.uni-tuebingen.de
FU Pharma 2100 ApS, Copenhagen, Denmark
FX Supported by Pharma 2100 ApS, Copenhagen, Denmark.
NR 40
TC 1
Z9 1
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0039-6060
J9 SURGERY
JI Surgery
PD JUN
PY 2010
VL 147
IS 6
BP 780
EP 788
DI 10.1016/j.surg.2009.11.003
PG 9
WC Surgery
SC Surgery
GA 607UM
UT WOS:000278532300004
PM 20045543
ER
PT J
AU Singer, EA
Bratslavsky, G
Linehan, WM
Srinivasan, R
AF Singer, Eric A.
Bratslavsky, Gennady
Linehan, W. Marston
Srinivasan, Ramaprasad
TI Targeted therapies for non-clear renal cell carcinoma
SO TARGETED ONCOLOGY
LA English
DT Review
DE Targeted therapy; Kidney cancer; Renal cell carcinoma; Non-clear cell;
Papillary; Chromophobe; Collecting duct
ID HOGG-DUBE-SYNDROME; COLLECTING DUCT CARCINOMA; QUALITY-OF-LIFE;
CYTOREDUCTIVE NEPHRECTOMY; INTERFERON-ALPHA; KIDNEY CANCER;
GENETIC-BASIS; SPONTANEOUS PNEUMOTHORAX; HISTOLOGIC SUBTYPES; RADICAL
NEPHRECTOMY
AB The treatment of advanced and metastatic kidney cancer has been revolutionized by the development of targeted systemic therapies. Despite the growing number of available agents approved for use against clear cell renal cell carcinoma, patients with non-clear histologies, constituting approximately 1 in 4 cases of kidney cancer, have not received the same attention. The majority of clinical trials testing novel targeted therapies have excluded non-clear subtypes, providing limited therapeutic options for patients with these diagnoses and their oncologists. This review will focus on the use of targeted therapies against the non-clear histologic subtypes of renal cell carcinoma: papillary I and II, chromophobe, and collecting duct. The unique genetic and molecular profiles of each distinct non-clear kidney cancer subtype will be described, as these differences are integral to the development and effectiveness of the novel agents used to treat them. Trials focusing on non-clear kidney cancer, or those that treated clear cell tumors along with significant numbers of non-clear subtypes, will be discussed. The role of cytoreductive nephrectomy and the use of neoadjuvant and adjuvant targeted therapy will be reviewed. Lastly, areas of future research will be highlighted.
C1 [Singer, Eric A.; Bratslavsky, Gennady; Linehan, W. Marston; Srinivasan, Ramaprasad] NCI, Dept Hlth & Human Serv, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Srinivasan, R (reprint author), NCI, Dept Hlth & Human Serv, Urol Oncol Branch, NIH, 10 Ctr Dr,Bldg 10,Rm 1-5940, Bethesda, MD 20892 USA.
EM singerea@mail.nih.gov; bratslag@mail.nih.gov; limehanm@mail.nih.gov;
ramasrin@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.
NR 85
TC 20
Z9 20
U1 0
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1776-2596
EI 1776-260X
J9 TARGET ONCOL
JI Target. Oncol.
PD JUN
PY 2010
VL 5
IS 2
BP 119
EP 129
DI 10.1007/s11523-010-0148-3
PG 11
WC Oncology
SC Oncology
GA 644QF
UT WOS:000281393900006
PM 20680492
ER
PT J
AU Conesa, A
Fernandez-Mestre, M
Padron, D
Toro, F
Silva, N
Tassinari, P
Blanca, I
Martin, MP
Carrington, M
Layrisse, Z
AF Conesa, A.
Fernandez-Mestre, M.
Padron, D.
Toro, F.
Silva, N.
Tassinari, P.
Blanca, I.
Martin, M. P.
Carrington, M.
Layrisse, Z.
TI Distribution of killer cell immunoglobulin-like receptor genes in the
mestizo population from Venezuela
SO TISSUE ANTIGENS
LA English
DT Article
DE KIR; mestizo Venezuelan population; natural killer cells; polymerase
chain reaction-sequence-specific primers
ID IG-LIKE RECEPTOR; KIR GENE; HLA-C; T-CELLS; DIVERSITY; MOLECULES;
ADMIXTURE; CLUSTER; CLONES; BLOOD
AB This study represents the first report on the distribution of KIR genes in 205 unrelated healthy mestizo Venezuelan individuals. Genotyping analysis showed that all KIR genes are present in this population. Frequency of inhibitory killer cell immunoglobulin-like receptors (KIRs) exceeded 0.69, except for KIR2DL2 (0.29) and 2DL5 (0.37). Activating KIRs showed low frequencies (0.11-0.29), except for KIR2DS4 (0.68). Forty-five different KIR genotypes were identified, with a predominance of three genotypes found in 50.7% of the population of which 25.9% were individuals homozygous for haplotype A. The frequencies of KIR genes reflect the ethnic admixture existing in the mestizo Venezuelan population.
C1 [Fernandez-Mestre, M.; Padron, D.; Layrisse, Z.] Inst Venezolano Invest Cient, Ctr Med Expt Miguel Layrisse, Caracas 1020A, Venezuela.
[Conesa, A.; Toro, F.; Silva, N.; Tassinari, P.; Blanca, I.] Cent Univ Venezuela, Fac Med, Inst Inmunol, FOCIS Ctr Excellence, Caracas, Venezuela.
[Martin, M. P.; Carrington, M.] NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Carrington, M.] Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA.
[Carrington, M.] Harvard Univ, Boston, MA 02115 USA.
RP Fernandez-Mestre, M (reprint author), Inst Venezolano Invest Cient, Ctr Med Expt Miguel Layrisse, Kilometro 11,Carretera Panamericana,Apdo 21827, Caracas 1020A, Venezuela.
EM mfernand@ivic.ve
FU FONACIT [G-2005000395, S1-2002000504]; National Cancer Institute,
National Institutes of Health [HHSN261200800001E]; NIH, National Cancer
Institute, Center for Cancer Research
FX This research was supported in part by FONACIT grants G-2005000395 and
S1-2002000504. This project has been funded in whole or in part with
federal funds from the National Cancer Institute, National Institutes of
Health, under contract no. HHSN261200800001E. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the
U.S. Government. This Research was supported in part by the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research. Our gratitude to the individuals who participated in
the study and to Omar Balbas for assistance with the Phylogeny Inference
Package.
NR 39
TC 1
Z9 2
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0001-2815
J9 TISSUE ANTIGENS
JI Tissue Antigens
PD JUN
PY 2010
VL 75
IS 6
BP 724
EP 729
DI 10.1111/j.1399-0039.2010.01446.x
PG 6
WC Cell Biology; Immunology; Pathology
SC Cell Biology; Immunology; Pathology
GA 595KJ
UT WOS:000277609000012
PM 20210918
ER
PT J
AU Godin, SJ
DeVito, MJ
Hughes, MF
Ross, DG
Scollon, EJ
Starr, JM
Setzer, RW
Conolly, RB
Tornero-Velez, R
AF Godin, Stephen J.
DeVito, Michael J.
Hughes, Michael F.
Ross, David G.
Scollon, Edward J.
Starr, James M.
Setzer, R. Woodrow
Conolly, Rory B.
Tornero-Velez, Rogelio
TI Physiologically Based Pharmacokinetic Modeling of Deltamethrin:
Development of a Rat and Human Diffusion-Limited Model
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE deltamethrin; physiologically based pharmacokinetic modeling;
pyrethroids; bioavailability; extrapolation
ID PYRETHROID INSECTICIDES; RISK-ASSESSMENT; MOTOR FUNCTION; METABOLISM;
EXPOSURE; TOXICOKINETICS; NEUROTOXICITY; ESFENVALERATE; CYPERMETHRIN;
POPULATION
AB Mirfazaelian et al. developed a physiologically based pharmacokinetic (PBPK) model for the pyrethroid pesticide deltamethrin in the rat. This model describes gastrointestinal (GI) tract absorption as a saturable process mediated by phase III efflux transporters which pump deltamethrin out of the intestinal enterocytes into the GI tract lumen, resulting in minimal net absorption at low concentrations and increasing absorption at higher concentrations. In the present study, the dose dependency in absorption of deltamethrin was examined in male Long Evans rats using po exposures predicted by the Mirfazaelian model to yield different po bioavailability values. No difference in the bioavailability from single po doses of 0.3 and 3.0 mg/kg deltamethrin was observed. Based on this finding, the Mirfazaelian PBPK model was modified to exclude a saturable absorption process. Other changes to the Mirfazaelian model included describing all tissue compartments with diffusion-limited kinetics and a single blood compartment. These changes improved model predictions of deltamethrin tissue concentration data from the present study and the literature. The rat model was then scaled to humans. The model predicted a twofold greater peak deltamethrin brain concentration and threefold greater area under the curve (AUC(0-48 h)) for humans following an po exposure of 1 mg/kg. Based on this model, humans would have greater distribution of deltamethrin to the brain for the same administered po dose compared to rats. The relative sensitivity to deltamethrin between rats and humans depends on both pharmacokinetic and pharmacodynamic differences. Species differences in the pharmacodynamic responses to deltamethrin between rats and humans remain uncharacterized.
C1 [Godin, Stephen J.] Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC USA.
[DeVito, Michael J.; Hughes, Michael F.; Ross, David G.; Scollon, Edward J.] Natl Hlth & Environm Effects Res Lab, Integrated Syst Toxicol Div, Res Triangle Pk, NC 27709 USA.
[Starr, James M.; Tornero-Velez, Rogelio] Burroughs Wellcome Co, Res Triangle Pk, NC 27709 USA.
[Setzer, R. Woodrow; Conolly, Rory B.] US EPA, Natl Ctr Computat Toxicol, Off Res & Dev, Res Triangle Pk, NC 27709 USA.
RP DeVito, MJ (reprint author), Natl Inst Environm Hlth Sci, Natl Toxicol Program, Toxicol Branch, POB 12233, Res Triangle Pk, NC 27709 USA.
EM devitom@niehs.nih.gov
FU U.S. Environmental Protection Agency; NHEEERL-DESE [EPA CT826513]
FX FUNDING; U.S. Environmental Protection Agency; NHEEERL-DESE (EPA
CT826513 to S.J.G.).
NR 38
TC 27
Z9 27
U1 0
U2 18
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
J9 TOXICOL SCI
JI Toxicol. Sci.
PD JUN
PY 2010
VL 115
IS 2
BP 330
EP 343
DI 10.1093/toxsci/kfq051
PG 14
WC Toxicology
SC Toxicology
GA 600OR
UT WOS:000277997100004
PM 20200215
ER
PT J
AU Boyd, WA
McBride, SJ
Rice, JR
Snyder, DW
Freedman, JH
AF Boyd, Windy A.
McBride, Sandra J.
Rice, Julie R.
Snyder, Daniel W.
Freedman, Jonathan H.
TI A high-throughput method for assessing chemical toxicity using a
Caenorhabditis elegans reproduction assay
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE Caenorhabditis elegans; High-throughput screening; Alternative
toxicological models; Cadmium
ID EGG-LAYING BEHAVIOR; C-ELEGANS; SIGNALING PATHWAYS; OXIDATIVE STRESS;
END-POINTS; MODEL; NEUROTOXICITY; LETHALITY; APOPTOSIS; SYSTEM
AB The National Research Council has outlined the need for non-mammalian toxicological models to test the potential health effects of a large number of chemicals while also reducing the use of traditional animal models. The nematode Caenorhabditis elegans is an attractive alternative model because of its well-characterized and evolutionarily conserved biology, low cost, and ability to be used in high-throughput screening. A high-throughput method is described for quantifying the reproductive capacity of C. elegans exposed to chemicals for 48 h from the last larval stage (L4) to adulthood using a COPAS Biosort. Initially, the effects of exposure conditions that could influence reproduction were defined. Concentrations of DMSO vehicle <= 1% did not affect reproduction. Previous studies indicated that C elegans may be influenced by exposure to low pH conditions. At pHs greater than 4.5, C. elegans reproduction was not affected; however below this pH there was a significant decrease in the number of offspring. Cadmium chloride was chosen as a model toxicant to verify that automated measurements were comparable to those of traditional observational studies. EC(50) values for cadmium for automated measurements (176-192 mu M) were comparable to those previously reported for a 72-h exposure using manual counting (151 mu M). The toxicity of seven test toxicants on C. elegans reproduction was highly correlative with rodent lethality suggesting that this assay may be useful in predicting the potential toxicity of chemicals in other organisms. Published by Elsevier Inc.
C1 [Boyd, Windy A.; Rice, Julie R.; Snyder, Daniel W.; Freedman, Jonathan H.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
[Freedman, Jonathan H.] NIEHS, Natl Toxicol Program, Biomol Screening Branch, Res Triangle Pk, NC 27709 USA.
RP Freedman, JH (reprint author), NIEHS, Mol Toxicol Lab, POB 12233,Mail Drop E1-05,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM freedma1@niehs.nih.gov
OI Boyd, Windy/0000-0003-3803-3716
FU National Institute of Environmental Health Sciences; National Institutes
of Health [Z01ES102045, Z01ES102046]; NIH National Center for Research
Resources (NCRR)
FX This work was supported in part by the National Toxicology Program, and
by the Intramural Research Program of the National Institute of
Environmental Health Sciences, National Institutes of Health
(Z01ES102045 and Z01ES102046). Nematode strains used in this work were
provided by the Caenorhabditis Genetics Center, which is funded by the
NIH National Center for Research Resources (NCRR). The authors would
like to thank Dr. Grace E. Kissling, Biostatistics Branch, NIEHS, for
statistical advice.
NR 45
TC 50
Z9 60
U1 3
U2 24
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 JUN 1
PY 2010
VL 245
IS 2
BP 153
EP +
DI 10.1016/j.taap.2010.02.014
PG 7
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 601SB
UT WOS:000278083100002
PM 20206647
ER
PT J
AU Marketon, JIW
Sternberg, EM
AF Marketon, Jeanette I. Webster
Sternberg, Esther M.
TI The Glucocorticoid Receptor: A Revisited Target for Toxins
SO TOXINS
LA English
DT Review
DE glucocorticoid receptor; toxins; anthrax lethal toxin; bacterial toxins;
environmental toxins
ID BLOOD MONONUCLEAR-CELLS; ANTHRAX LETHAL FACTOR; MEDIATED
GENE-TRANSCRIPTION; REUBER HEPATOMA-CELLS; RAT-LIVER NUCLEI; RHEUMATIC
AUTOIMMUNE DISORDERS; INFLAMMATORY-BOWEL-DISEASE; MESSENGER-RNA
EXPRESSION; P-GLYCOPROTEIN ACTIVITY; ACUTE-PHASE RESPONSE
AB The hypothalamic-pituitary-adrenal (HPA) axis activation and glucocorticoid responses are critical for survival from a number of bacterial, viral and toxic insults, demonstrated by the fact that removal of the HPA axis or GR blockade enhances mortality rates. Replacement with synthetic glucocorticoids reverses these effects by providing protection against lethal effects. Glucocorticoid resistance/insensitivity is a common problem in the treatment of many diseases. Much research has focused on the molecular mechanism behind this resistance, but an area that has been neglected is the role of infectious agents and toxins. We have recently shown that the anthrax lethal toxin is able to repress glucocorticoid receptor function. Data suggesting that the glucocorticoid receptor may be a target for a variety of toxins is reviewed here. These studies have important implications for glucocorticoid therapy.
C1 [Marketon, Jeanette I. Webster] Dept Internal Med, Div Pulm Allergy Crit Care & Sleep Med, Columbus, OH 43210 USA.
[Marketon, Jeanette I. Webster] Ohio State Univ, Med Ctr, Inst Behav Med Res, Columbus, OH 43210 USA.
[Sternberg, Esther M.] NIMH, US Dept HHS, Sect Neuroendocrine Immunol & Behav, NIH, Bethesda, MD 20892 USA.
RP Marketon, JIW (reprint author), Dept Internal Med, Div Pulm Allergy Crit Care & Sleep Med, 201 DHLRI,473 W 12th Ave, Columbus, OH 43210 USA.
EM jeanette.marketon@osumc.edu; sternbee@mail.nih.gov
NR 177
TC 8
Z9 8
U1 1
U2 8
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 2072-6651
J9 TOXINS
JI Toxins
PD JUN
PY 2010
VL 2
IS 6
BP 1357
EP 1380
DI 10.3390/toxins2061357
PG 24
WC Toxicology
SC Toxicology
GA V24UJ
UT WOS:000208435000010
PM 22069642
ER
PT J
AU Jian, XY
Cavenagh, M
Gruschus, JM
Randazzo, PA
Kahn, RA
AF Jian, Xiaoying
Cavenagh, Margaret
Gruschus, James M.
Randazzo, Paul A.
Kahn, Richard A.
TI Modifications to the C-Terminus of Arf1 Alter Cell Functions and Protein
Interactions
SO TRAFFIC
LA English
DT Article
DE Arf; ArfGAP; ArfGEF; GFP; GST
ID ADP-RIBOSYLATION FACTOR; GUANINE-NUCLEOTIDE-EXCHANGE; GTP-BINDING
PROTEINS; COPII VESICLE COAT; SACCHAROMYCES-CEREVISIAE; MUTATIONAL
ANALYSIS; ACTIVATING PROTEIN; KINETIC-ANALYSIS; GOLGI-COMPLEX;
CHOLERA-TOXIN
AB Arf family proteins are approximate to 21-kDa GTP-binding proteins that are critical regulators of membrane traffic and the actin cytoskeleton. Studies examining the complex signaling pathways underlying Arf action have relied on recombinant proteins comprised of Arf fused to epitope tags or proteins, such as glutathione S-transferase or green fluorescent protein, for both cell-based mammalian cell studies and bacterially expressed recombinant proteins for biochemical assays. However, the effects of such protein fusions on the biochemical properties relevant to the cellular function have been only incompletely studied at best. Here, we have characterized the effect of C-terminal tagging of Arf1 on (i) function in Saccharomyces cerevisiae, (ii) in vitro nucleotide exchange and (iii) interaction with guanine nucleotide exchange factors and GTPase-activating proteins. We found that the tagged Arfs were substantially impaired or altered in each assay, compared with the wild-type protein, and these changes are certain to alter actions in cells. We discuss the results related to the interpretation of experiments using these reagents and we propose that authors and editors consistently adopt a few simple rules for describing and discussing results obtained with Arf family members that can be readily applied to other proteins.
C1 [Jian, Xiaoying; Randazzo, Paul A.] NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA.
[Cavenagh, Margaret] NCI, Canc Diag Program, Bethesda, MD 20892 USA.
[Gruschus, James M.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Kahn, Richard A.] Emory Univ, Dept Biochem, Atlanta, GA 30322 USA.
RP Randazzo, PA (reprint author), NCI, Cellular & Mol Biol Lab, Bldg 37,Room 2042, Bethesda, MD 20892 USA.
EM randazzp@mail.nih.gov
FU National Cancer Institute; National Institutes of Health; NIGMS
[GM-61268, GM-67226]
FX We thank Stephen Garrett (UMDNJ-New Jersey Medical School) for
generously sharing his unpublished data and providing strains and
plasmids containing arf1-26. James Prestegard (University of Georgia),
Stephen Garret, Julie Donaldson (National Heart, Lung and Blood
Institute) and Jonathan Goldberg (Memorial Sloan-Kettering) provided
insightful and helpful discussions. We are also indebted to Julie
Donaldson, James E. Casanova (University of Virginia) and Elizabeth
Sztul (University of Alabama, Birmingham) for reading and critiquing
drafts of the manuscript. The work was supported by the Intramural
Program of the National Cancer Institute, the National Institutes of
Health (J.M.G., X.J.,M. C. and P. A. R.) and by extramural support from
NIGMS (GM-61268 and GM-67226; R. A. K.).
NR 59
TC 17
Z9 17
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-9219
EI 1600-0854
J9 TRAFFIC
JI Traffic
PD JUN
PY 2010
VL 11
IS 6
BP 732
EP 742
DI 10.1111/j.1600-0854.2010.01054.x
PG 11
WC Cell Biology
SC Cell Biology
GA 594IE
UT WOS:000277529300002
PM 20214751
ER
PT J
AU Glynn, SA
AF Glynn, Simone A.
TI The red blood cell storage lesion: a method to the madness
SO TRANSFUSION
LA English
DT Editorial Material
ID STORED RBCS; DURATION; OLD
C1 NHLBI, DBDR, Bethesda, MD 20892 USA.
RP Glynn, SA (reprint author), NHLBI, DBDR, Bldg 10, Bethesda, MD 20892 USA.
EM glynnsa@nhlbi.nih.gov
NR 15
TC 46
Z9 49
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD JUN
PY 2010
VL 50
IS 6
BP 1164
EP 1169
PG 6
WC Hematology
SC Hematology
GA 604ZH
UT WOS:000278316500002
PM 20598098
ER
PT J
AU Bryant, BJ
Yau, YY
Byrne, PJ
Stroncek, DF
Leitman, SF
AF Bryant, Barbara J.
Yau, Yu Ying
Byrne, Phyllis J.
Stroncek, David F.
Leitman, Susan F.
TI Gravity sedimentation of granulocytapheresis concentrates with
hydroxyethyl starch efficiently removes red blood cells and retains
neutrophils
SO TRANSFUSION
LA English
DT Article
ID NEUTROPENIC PATIENTS; STIMULATING FACTOR; G-CSF; TRANSFUSION THERAPY;
INFECTIONS; EFFICACY; DONORS; DEXAMETHASONE; TRANSPLANTATION;
GRANULOCYTES
AB BACKGROUND:
Transfusion of granulocytapheresis concentrates can be limited by the volume of incompatible donor red blood cells (RBCs) in the component. Efficient reduction of RBCs in granulocyte units would result in safe transfusion of RBC-incompatible units.
STUDY DESIGN AND METHODS:
Granulocyte concentrates were collected by continuous-flow apheresis from granulocyte-colony-stimulating factor (G-CSF) and dexamethasone-stimulated volunteer donors, with 6% hydroxyethyl starch (HES) added continuously during apheresis as a RBC sedimenting agent to enhance granulocyte collection efficiency. After collection, the component was placed in a plasma extractor for 4 hours. A sharp line of demarcation between the starch-sedimented RBCs and the granulocyte-rich supernatant developed, and the supernatant was transferred to a sterilely docked transfer pack. RBC reduction and white blood cell recovery were determined.
RESULTS:
Gravity sedimentation was performed on 165 granulocyte concentrates. Mean sedimentation time was 267 minutes (range, 150-440 min). RBC depletion was 92% (range, 71%-99%) with mean residual RBC content of 3.2 +/- 1.4 mL. Twelve percent of components contained less than 2 mL of RBCs. Mean granulocyte and platelet (PLT) recoveries were 80 and 81%, respectively. There were no transfusion reactions or signs of hemolysis after transfusion of 66 RBC-incompatible granulocyte concentrates (RBC volume, 1.6-8.2 mL). The remaining concentrates were used for topical or intrapleural applications.
CONCLUSIONS:
RBCs were significantly reduced and granulocytes and PLTs effectively retained in G-CSF/steroid-mobilized granulocyte components collected with HES and processed by gravity sedimentation. This procedure allows safe transfusion of RBC-incompatible sedimented granulocyte units and may be used to expand the pool of available granulocyte donors for specific recipients.
C1 [Bryant, Barbara J.; Yau, Yu Ying; Byrne, Phyllis J.; Stroncek, David F.; Leitman, Susan F.] NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA.
RP Bryant, BJ (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bldg 10,Room 1C711, Bethesda, MD 20892 USA.
EM bryantb2@cc.nih.gov
FU Intramural NIH HHS [ZIA CL002124-01]
NR 22
TC 5
Z9 5
U1 1
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 JUN
PY 2010
VL 50
IS 6
BP 1203
EP 1209
DI 10.1111/j.1537-2995.2009.02576.x
PG 7
WC Hematology
SC Hematology
GA 604ZH
UT WOS:000278316500009
PM 20113453
ER
PT J
AU Kakaiya, RM
Triulzi, DJ
Wright, DJ
Steele, WR
Kleinman, SH
Busch, MP
Norris, PJ
Hillyer, CD
Gottschall, JL
Rios, JA
Carey, P
Glynn, SA
AF Kakaiya, Ram M.
Triulzi, Darrell J.
Wright, David J.
Steele, Whitney R.
Kleinman, Steven H.
Busch, Michael P.
Norris, Philip J.
Hillyer, Christopher D.
Gottschall, Jerome L.
Rios, Jorge A.
Carey, Patricia
Glynn, Simone A.
CA NHLBI Retrovirus Epidemiology Dono
TI Prevalence of HLA antibodies in remotely transfused or alloexposed
volunteer blood donors
SO TRANSFUSION
LA English
DT Article
ID ACUTE LUNG INJURY; ALLOIMMUNIZATION; REDUCTION
AB BACKGROUND:
HLA antibody testing of previously transfused or pregnant donors may help reduce the risk of transfusion-related acute lung injury (TRALI). However, the prevalence of HLA antibodies in transfused donors has not been well characterized.
STUDY DESIGN AND METHODS:
Transfusion and pregnancy history was obtained from consenting donors. HLA Class I and II antibody testing was performed by multiantigen bead Luminex platform. Cutoff values for Class I and II antibodies used normalized background ratios of 10.8 and 6.9, respectively. Linear probability models were used to evaluate potential associations between HLA alloimmunization and donor characteristics.
RESULTS:
A total of 7920 donors (2086 males and 5834 females) were tested. HLA antibody prevalence did not significantly differ between 895 transfused (1.7%) and 1138 nontransfused males (1.0%; odds ratio [OR], 1.75; 95% confidence interval [CI], 0.80-3.82]. Prevalence in 45 transfused nulliparous females (4.4%; 95% CI, 0.1%-11.8%) was not different from the 1.6% prevalence in 1732 nontransfused nulliparous females (OR, 2.94; 95% CI, 0.68-12.74). Transfused parous females had higher prevalence than nontransfused counterparts (p = 0.004; OR, 1.39; 95% CI, 1.07-1.80). In a linear probability model, the estimated additive risk of transfusion-induced alloimmunization was only 0.8% (95% CI, -0.2% to 1.8%; p = 0.10). Donor transfusion history showed that 58% of transfusions occurred more than 10 years previously.
CONCLUSION:
Transfused volunteer blood donors do not appear to have a significantly higher prevalence of HLA antibodies than their nontransfused counterparts. Thus, in an effort to reduce TRALI risk, ascertaining past history of transfusion and testing these donors for HLA antibodies is not necessary.
C1 [Kakaiya, Ram M.] LifeSource, Glenview, IL 60025 USA.
Inst Transfus Med, Pittsburgh, PA USA.
Westat Corp, Rockville, MD USA.
Univ Calif San Francisco, Blood Syst Res Inst, San Francisco, CA 94143 USA.
Emory Univ So Reg, Amer Red Cross Blood Serv, Atlanta, GA USA.
Amer Red Cross Blood Serv, Dedham, MA USA.
BloodCtr Wisconsin, Milwaukee, WI USA.
Univ Cincinnati, Acad Hlth Ctr, Hoxworth Blood Ctr, Cincinnati, OH USA.
NHLBI, Bethesda, MD 20892 USA.
RP Kakaiya, RM (reprint author), LifeSource, 1205 N Milwaukee Ave, Glenview, IL 60025 USA.
EM rkakaiya@itxm.org
OI Carey, Patricia/0000-0001-8706-280X
FU NHLBI [N01-HB-47168, N01-HB-47169, N01-HB-47170, N01-HB-47171,
N01-HB-47172, N01-HB-47175, N01-HB-57181]
FX This work was supported by NHLBI Contracts N01-HB-47168, -47169, -47170,
-47171, -47172, -47175, and -57181.
NR 13
TC 34
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U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD JUN
PY 2010
VL 50
IS 6
BP 1328
EP 1334
DI 10.1111/j.1537-2995.2009.02556.x
PG 7
WC Hematology
SC Hematology
GA 604ZH
UT WOS:000278316500023
PM 20070615
ER
PT J
AU Casanova, MF
El-Baz, A
Elnakib, A
Giedd, J
Rumsey, JM
Williams, EL
Switala, AE
AF Casanova, Manuel F.
El-Baz, Ayman
Elnakib, Ahmed
Giedd, Jay
Rumsey, Judith M.
Williams, Emily L.
Switala, Andrew E.
TI CORPUS CALLOSUM SHAPE ANALYSIS WITH APPLICATION TO DYSLEXIA
SO TRANSLATIONAL NEUROSCIENCE
LA English
DT Article
DE Brain mapping; Corpus callosum; Dyslexia; Magnetic resonance imaging
AB Morphometric studies of the corpus callosum suggest its involvement in a number of psychiatric conditions. In the present study we introduce a novel pattern recognition technique that offers a point-by-point shape descriptor of the corpus callosum. The method uses arc lengths of electric field lines in order to avoid discontinuities caused by folding anatomical contours. We tested this technique by comparing the shape of the corpus callosum in a series of dyslexic men (n = 16) and age-matched controls (n = 14). The results indicate a generalized increase in size of the corpus callosum in dyslexia with a concomitant diminution at its rostral and caudal poles. The reported shape analysis and 2D-reconstruction provide information of anatomical importance that would otherwise passed unnoticed when analyzing size information alone.
C1 [Casanova, Manuel F.; Switala, Andrew E.] Univ Louisville, Dept Psychiat & Behav Sci, Louisville, KY 40202 USA.
[El-Baz, Ayman; Elnakib, Ahmed] Univ Louisville, Dept Bioengn, Louisville, KY 40202 USA.
[Giedd, Jay] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA.
[Rumsey, Judith M.] NIMH, Div Adult Translat Res, Bethesda, MD 20892 USA.
[Williams, Emily L.] Univ Louisville, Dept Anat Sci & Neurobiol, Louisville, KY 40202 USA.
RP Casanova, MF (reprint author), Univ Louisville, Dept Psychiat & Behav Sci, Louisville, KY 40202 USA.
EM m0casa02@louisville.edu
RI Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015;
OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; Elnakib,
Ahmed/0000-0001-6084-3622; El-Baz, Ayman/0000-0001-7264-1323
FU NIH [R01 MH86784, R01 MH88893]
FX Funding for this work was provided by NIH grants R01 MH86784 and R01
MH88893. The series of patients and controls were collected under the
guidance and support of Dr. Judith Rapoport, Chief of the Child
Psychiatry Branch at the National Institute of Mental Health (NIMH). We
thank Desha M. Jordan, Sabrina C. Rainey, and Dr. Robert L. Falk for
assisting with manual segmentation of the corpus callosum.
NR 49
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U1 3
U2 5
PU VERSITA
PI WARSAW
PA SOLIPSKA 14A-1, 02-482 WARSAW, POLAND
SN 2081-3856
J9 TRANSL NEUROSCI
JI Transl. Neurosci.
PD JUN
PY 2010
VL 1
IS 2
BP 124
EP 130
DI 10.2478/v10134-010-0017-8
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA V20PY
UT WOS:000208153100005
PM 22545196
ER
PT J
AU Op de Beeck, HP
Baker, CI
AF Op de Beeck, Hans P.
Baker, Chris I.
TI Informativeness and learning: Response to Gauthier and colleagues
SO TRENDS IN COGNITIVE SCIENCES
LA English
DT Letter
ID EXPERTISE; AREA
C1 [Op de Beeck, Hans P.] Univ Leuven KU Leuven, Lab Biol Psychol, B-3000 Louvain, Belgium.
[Baker, Chris I.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
RP Op de Beeck, HP (reprint author), Univ Leuven KU Leuven, Lab Biol Psychol, Tiensestr 102, B-3000 Louvain, Belgium.
EM hans.opdebeeck@psy.kuleuven.be; bakerchris@mail.nih.gov
OI Baker, Chris/0000-0001-6861-8964
FU Intramural NIH HHS [Z01 MH002893-02]
NR 7
TC 3
Z9 3
U1 0
U2 3
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 1364-6613
J9 TRENDS COGN SCI
JI TRENDS COGN. SCI.
PD JUN
PY 2010
VL 14
IS 6
BP 236
EP 237
DI 10.1016/j.tics.2010.03.010
PG 2
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA 614WA
UT WOS:000279089300004
PM 20714344
ER
PT J
AU Yang, L
Pang, YL
Moses, HL
AF Yang, Li
Pang, Yanli
Moses, Harold L.
TI TGF-beta and immune cells: an important regulatory axis in the tumor
microenvironment and progression
SO TRENDS IN IMMUNOLOGY
LA English
DT Review
ID GROWTH-FACTOR-BETA; NF-KAPPA-B; T-CELLS; MYELOID CELLS; COLON-CANCER;
PROMOTE METASTASIS; LUNG METASTASIS; BREAST-CANCER; IN-VIVO;
INFLAMMATION
AB Transforming growth factor beta (TGF-beta) plays an important role in tumor initiation and progression, functioning as both a suppressor and a promoter. The mechanisms underlying this dual role of TGF-beta remain unclear. TGF-beta exerts systemic immune suppression and inhibits host immunosurveillance. Neutralizing TGF-beta enhances CD8+ T-cell- and NK-cell-mediated anti-tumor immune responses. It also increases neutrophil-attracting chemokines resulting in recruitment and activation of neutrophils with an antitumor phenotype. In addition to its systemic effects, TGF-beta regulates infiltration of inflammatory/immune cells and cancer-associated fibroblasts in the tumor miwcroenvironment causing direct changes in tumor cells. Understanding TGF-beta regulation at the interface of tumor and host immunity should provide insights into developing effective TGF-beta antagonists and biomarkers for patient selection and efficacy of TGF-beta antagonist treatment.
C1 [Yang, Li; Pang, Yanli] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20876 USA.
[Moses, Harold L.] Vanderbilt Univ, Sch Med, Dept Canc Biol, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA.
RP Yang, L (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20876 USA.
EM yangl3@mail.nih.gov
FU Intramural NIH HHS [ZIA BC011163-01]
NR 86
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U1 10
U2 58
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1471-4906
J9 TRENDS IMMUNOL
JI Trends Immunol.
PD JUN
PY 2010
VL 31
IS 6
BP 220
EP 227
DI 10.1016/j.it.2010.04.002
PG 8
WC Immunology
SC Immunology
GA 619JR
UT WOS:000279427000003
PM 20538542
ER
PT J
AU Miller, DS
AF Miller, David S.
TI Regulation of P-glycoprotein and other ABC drug transporters at the
blood-brain barrier
SO TRENDS IN PHARMACOLOGICAL SCIENCES
LA English
DT Review
ID CANCER RESISTANCE PROTEIN; PREGNANE-X-RECEPTOR; CENTRAL-NERVOUS-SYSTEM;
DIESEL EXHAUST PARTICLES; NECROSIS-FACTOR-ALPHA; ENDOTHELIAL-CELLS;
MULTIDRUG-RESISTANCE; UP-REGULATION; IN-VIVO; AMYLOID-BETA
AB ATP-binding cassette (ABC) transporters are important selective elements of the blood-brain barrier. They line the luminal plasma membrane of the brain capillary endothelium, facing the vascular space, and both protect the central nervous system from entry of neurotoxicants and limit the access of therapeutic drugs to the brain parenchyma. Recent studies highlight the multiple signaling pathways through which the expression and activity of P-glycoprotein and other ABC transporters are modulated in response to xenobiotics, stress and disease. The results show that increased transporter expression occurs in response to signals that activate specific transcription factors, including pregnane-X receptor, constitutive androstane receptor, nuclear factor-kappa B and activator protein-1, and that reduced transporter activity occurs rapidly and reversibly in response to signaling through Src kinase, protein kinase C and estrogen receptors. A detailed understanding of such regulation can provide the basis for improved neuroprotection and enhanced therapeutic drug delivery to the brain.
C1 NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
RP Miller, DS (reprint author), NIEHS, Lab Toxicol & Pharmacol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM miller@niehs.nih.gov
FU NIH, National Institute of Environmental Health Sciences
FX My work is supported by the Intramural Research Program of the NIH,
National Institute of Environmental Health Sciences. I thank current and
past members of the Miller Laboratory for helpful discussions.
NR 77
TC 166
Z9 174
U1 4
U2 33
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0165-6147
J9 TRENDS PHARMACOL SCI
JI Trends Pharmacol. Sci.
PD JUN
PY 2010
VL 31
IS 6
BP 246
EP 254
DI 10.1016/j.tips.2010.03.003
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 619JP
UT WOS:000279426800002
PM 20417575
ER
PT J
AU Mayer, AMS
Glaser, KB
Cuevas, C
Jacobs, RS
Kem, W
Little, RD
McIntosh, JM
Newman, DJ
Potts, BC
Shuster, DE
AF Mayer, Alejandro M. S.
Glaser, Keith B.
Cuevas, Carmen
Jacobs, Robert S.
Kem, William
Little, R. Daniel
McIntosh, J. Michael
Newman, David J.
Potts, Barbara C.
Shuster, Dale E.
TI The odyssey of marine pharmaceuticals: a current pipeline perspective
SO TRENDS IN PHARMACOLOGICAL SCIENCES
LA English
DT Review
ID WHIP PSEUDOPTEROGORGIA-ELISABETHAE; ALPHA-7 NICOTINIC AGONIST;
GROWTH-FACTOR RECEPTOR; SOFT-TISSUE SARCOMA; CANCER-CELL-LINES;
IN-VITRO; PHASE-I; ANTIMITOTIC MECHANISM; PROTEASOME INHIBITOR;
NUCLEOTIDE-EXCISION
AB The global marine pharmaceutical pipeline consists of three Food and Drug Administration (FDA) approved drugs, one EU registered drug, 13 natural products (or derivatives thereof) in different phases of the clinical pipeline and a large number of marine chemicals in the preclinical pipeline. In the United States there are three FDA approved marine-derived drugs, namely cytarabine (Cytosar-U (R), Depocyt (R)), vidarabine (Vira-A (R)) and ziconotide (Prialt (R)). The current clinical pipeline includes 13 marine-derived compounds that are either in Phase I, Phase II or Phase III clinical trials. Several key Phase III studies are ongoing and there are seven marine-derived compounds now in Phase II trials. The preclinical pipeline continues to supply several hundred novel marine compounds every year and those continue to feed the clinical pipeline with potentially valuable compounds. From a global perspective the marine pharmaceutical pipeline remains very active, and now has sufficient momentum to deliver several additional compounds to the marketplace in the near future; this review provides a current view of the pipeline.
C1 [Mayer, Alejandro M. S.; Glaser, Keith B.] Midwestern Univ, Chicago Coll Osteopath Med, Dept Pharmacol, Downers Grove, IL 60515 USA.
[Glaser, Keith B.] Abbott Labs, Abbott Pk, IL 60064 USA.
[Cuevas, Carmen] R&D PharmaMar, Res & Dev Director, Madrid 28770, Spain.
[Little, R. Daniel] Univ Calif Santa Barbara, Dept Chem & Biochem, Santa Barbara, CA 93106 USA.
[Kem, William] Univ Florida, Coll Med, Dept Pharmacol & Therapeut, Gainesville, FL 32610 USA.
[McIntosh, J. Michael] Univ Utah, Dept Psychiat, Salt Lake City, UT 84112 USA.
[Newman, David J.] NCI, Nat Prod Branch, Frederick, MD 21701 USA.
[Potts, Barbara C.] Nereus Pharmaceut Inc, San Diego, CA 92121 USA.
[Shuster, Dale E.] Eisai Inc, Oncol, Woodcliff Lake, NJ 07677 USA.
RP Mayer, AMS (reprint author), Midwestern Univ, Chicago Coll Osteopath Med, Dept Pharmacol, 555 31st St, Downers Grove, IL 60515 USA.
EM amayer@midwestern.edu
OI Mayer, Alejandro /0000-0002-8358-4528
FU Midwestern University
FX This marine pharmaceuticals review was made possible with financial
support from Midwestern University to A.M.S.M. Assistance with searches
of the marine pharmaceutical literature in PubMed, Marinlit, Current
Contents (R) and Chemical Abstracts (R), as well as article retrieval by
library staff members, medical and pharmacy students of Midwestern
University, is most gratefully acknowledged. The authors are especially
thankful to Ms. Mary Hall for careful help in the preparation of this
manuscript.
NR 97
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U1 8
U2 83
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0165-6147
J9 TRENDS PHARMACOL SCI
JI Trends Pharmacol. Sci.
PD JUN
PY 2010
VL 31
IS 6
BP 255
EP 265
DI 10.1016/j.tips.2010.02.005
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 619JP
UT WOS:000279426800003
PM 20363514
ER
PT J
AU Willemsen, G
de Geus, EJC
Bartels, M
van Beijsterveldt, CEMT
Brooks, AI
Estourgie-van Burk, GF
Fugman, DA
Hoekstra, C
Hottenga, JJ
Kluft, K
Meijer, P
Montgomery, GW
Rizzu, P
Sondervan, D
Smit, AB
Spijker, S
Suchiman, HED
Tischfield, JA
Lehner, T
Slagboom, PE
Boomsma, DI
AF Willemsen, Gonneke
de Geus, Eco J. C.
Bartels, Meike
van Beijsterveldt, C. E. M. Toos
Brooks, Andy I.
Estourgie-van Burk, G. Frederique
Fugman, Douglas A.
Hoekstra, Chantal
Hottenga, Jouke-Jan
Kluft, Kees
Meijer, Piet
Montgomery, Grant W.
Rizzu, Patrizia
Sondervan, David
Smit, August B.
Spijker, Sabine
Suchiman, H. Eka D.
Tischfield, Jay A.
Lehner, Thomas
Slagboom, P. Eline
Boomsma, Dorret I.
TI The Netherlands Twin Register Biobank: A Resource for Genetic
Epidemiological Studies
SO TWIN RESEARCH AND HUMAN GENETICS
LA English
DT Article
DE DNA; RNA; GWAS; mental health; physical health
ID GENOME-WIDE ASSOCIATION; MAJOR DEPRESSIVE DISORDER; LOCI; HERITABILITY;
POPULATIONS; VARIANTS; FAMILIES; BEHAVIOR; SAMPLES; DESIGN
AB In 2004 the Netherlands Twin Register (NTR) started I a large scale biological sample collection in twin families to create a resource for genetic studies on health, lifestyle and personality. Between January 2004 and July 2008, adult participants from NTR research projects were invited into the study. During a home visit between 7:00 and 10:00 am, fasting blood and morning urine samples were collected. Fertile women were bled on day 2-4 of the menstrual cycle, or in their pill-free week. Biological samples were collected for DNA isolation, gene expression studies, creation of cell lines and for biomarker assessment. At the time of blood sampling, additional phenotypic information concerning health, medication use, body composition and smoking was collected. Of the participants contacted, 69% participated. Blood and urine samples were collected in 9,530 participants (63% female, average age 44.4 (SD 15.5) years) from 3,477 families. Lipid profile, glucose, insulin, HbA1c, haematology, CRP, fibrinogen, liver enzymes and creatinine have been assessed. Longitudinal survey data on health, personality and lifestyle are currently available for 90% of all participants. Genome-wide SNP data are available for 3,524 participants, with additional genotyping ongoing. The NTR biobank, combined with the extensive phenotypic information available within the NTR, provides a valuable resource for the study of genetic determinants of individual differences in mental and physical health. It offers opportunities for DNA-based and gene expression studies as well as for future metabolomic and proteomic projects.
C1 [Willemsen, Gonneke; de Geus, Eco J. C.; Bartels, Meike; van Beijsterveldt, C. E. M. Toos; Estourgie-van Burk, G. Frederique; Hoekstra, Chantal; Hottenga, Jouke-Jan; Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.
[Brooks, Andy I.; Fugman, Douglas A.; Tischfield, Jay A.] Rutgers State Univ, Rutgers Univ Cell & DNA Repository, Dept Genet, Piscataway, NJ USA.
[Kluft, Kees; Meijer, Piet] TNO Qual Life, Gaubius Lab, Biomed Res, Leiden, Netherlands.
[Kluft, Kees; Meijer, Piet] Good Biomarker Sci, Leiden, Netherlands.
[Montgomery, Grant W.] Queensland Inst Med Res, Herston, Qld 4006, Australia.
[Rizzu, Patrizia; Sondervan, David] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Amsterdam, Netherlands.
[Smit, August B.; Spijker, Sabine] Vrije Univ Amsterdam, Dept Mol & Cellular Neurobiol, Amsterdam, Netherlands.
[Suchiman, H. Eka D.; Slagboom, P. Eline] Leiden Univ, Med Ctr, Dept Med Stat & Bioinformat, NL-2300 RA Leiden, Netherlands.
[Lehner, Thomas] NIMH, Div Neurosci & Basic Behav Sci, NIH, Bethesda, MD 20892 USA.
RP Willemsen, G (reprint author), Vrije Univ Amsterdam, Dept Biol Psychol, Boechorststr 1, Amsterdam, Netherlands.
EM ahm.willemsen@psy.vu.nl
RI Smit, August /E-8410-2011; Spijker, Sabine/F-2300-2011; Bartels,
Meike/D-4492-2014; de Geus, Eco/M-9318-2015; Montgomery,
Grant/B-7148-2008; Slagboom, P. Eline/R-4790-2016;
OI Bartels, Meike/0000-0002-9667-7555; de Geus, Eco/0000-0001-6022-2666;
Montgomery, Grant/0000-0002-4140-8139; Slagboom, P.
Eline/0000-0002-2875-4723; Tischfield, Jay/0000-0003-3217-8287
FU NIMH NIH HHS [1RC2MH089951-01, U24 MH068457-06]; PHS HHS
[R01D0042157-01A]
NR 32
TC 61
Z9 61
U1 0
U2 8
PU AUSTRALIAN ACAD PRESS
PI BOWEN HILLS
PA 32 JEAYS ST, BOWEN HILLS, QLD 4006, AUSTRALIA
SN 1832-4274
J9 TWIN RES HUM GENET
JI Twin Res. Hum. Genet.
PD JUN
PY 2010
VL 13
IS 3
BP 231
EP 245
PG 15
WC Genetics & Heredity; Obstetrics & Gynecology
SC Genetics & Heredity; Obstetrics & Gynecology
GA 729ZX
UT WOS:000287994300002
PM 20477721
ER
PT J
AU Augustine, AD
Cassetti, MC
Ennis, FA
Harris, E
Hildebrand, WH
Repik, PM
AF Augustine, Alison D.
Cassetti, M. Cristina
Ennis, Francis A.
Harris, Eva
Hildebrand, William H.
Repik, Patricia M.
TI NIAID Workshop on Flavivirus Immunity
SO VIRAL IMMUNOLOGY
LA English
DT Editorial Material
ID WEST-NILE-VIRUS; YELLOW-FEVER VACCINATION; TICK-BORNE ENCEPHALITIS;
VISCEROTROPIC DISEASE; TRANSMISSION; INFECTIONS; SEVERITY
AB On September 16, 2009, the National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health, convened a workshop to discuss current knowledge of T- and B-cell immune epitopes for members of the Flavivirus genus (family Flaviviridae), and how this information could be used to increase our basic understanding of host-pathogen interactions and/or advance the development of new or improved vaccines and diagnostics for these pathogens. B-cell and T-cell responses to flaviviruses are critical components of protective immunity against these pathogens. However, they have also been linked to disease pathogenesis. A detailed understanding of the biological significance of immune epitope information may provide clues regarding the mechanisms governing the induction of protective versus pathogenic adaptive immune responses.
C1 [Augustine, Alison D.] NIAID, NIH, DHHS, Bethesda, MD 20892 USA.
[Ennis, Francis A.] Univ Massachusetts, Sch Med, Ctr Infect Dis & Vaccine Res, Worcester, MA USA.
[Harris, Eva] Univ Calif Berkeley, Sch Publ Hlth, Div Infect Dis & Vaccionol, Berkeley, CA 94720 USA.
[Hildebrand, William H.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
RP Augustine, AD (reprint author), NIAID, NIH, DHHS, 6610 Rockledge Dr,Room 6415, Bethesda, MD 20892 USA.
EM augustine@niaid.nih.gov
NR 32
TC 1
Z9 1
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0882-8245
J9 VIRAL IMMUNOL
JI Viral Immunol.
PD JUN
PY 2010
VL 23
IS 3
BP 235
EP 240
DI 10.1089/vim.2009.0114
PG 6
WC Immunology; Virology
SC Immunology; Virology
GA 613JE
UT WOS:000278974400002
PM 20565288
ER
PT J
AU Xiao, S
Subbiah, M
Kumar, S
De Nardi, R
Terregino, C
Collins, PL
Samal, SK
AF Xiao, Sa
Subbiah, Madhuri
Kumar, Sachin
De Nardi, Roberta
Terregino, Calogero
Collins, Peter L.
Samal, Siba K.
TI Complete genome sequences of avian paramyxovirus serotype 6 prototype
strain Hong Kong and a recent novel strain from Italy: Evidence for the
existence of subgroups within the serotype
SO VIRUS RESEARCH
LA English
DT Article
DE Avian paramyxovirus; APMV-6; Strain Italy; Genome sequence
ID RESPIRATORY SYNCYTIAL VIRUS; NEWCASTLE-DISEASE VIRUS; SH GENE;
GLYCOPROTEIN; PATHOGENICITY; POULTRY; PROTEIN; SITE; INFECTIVITY;
PREVALENCE
AB Complete genome sequences were determined for two strains of avian paramyxovirus serotype 6 (APMV-6): the prototype Hong Kong (HK) strain and a more recent isolate from Italy (IT4524-2). The genome length of strain HK is 16236 nucleotide (nt), which is the same as for the other two APMV-6 strains (FE and 7W) that have been reported to date, whereas that of strain IT4524-2 is 16230 nt. The length difference in strain IT4524-2 is due to a 6-nt deletion in the downstream untranslated region of the F gene. All of these viruses follow the "rule of six". Each genome consists of seven genes in the order of 3'N-P-M-F-SH-HN-L5', which differs from other APMV serotypes in containing an additional gene encoding the small hydrophobic (SH) protein. Sequence comparisons revealed that strain IT4524-2 shares an unexpectedly low level of genome nt sequence identity (70%) and aggregate predicted amino acid (aa) sequence identity (79%) with other three strains, which in contrast are more closely related to each other with nt sequence 94-98% nt identity and 90-100% aggregate aa identity. Sequence analysis of the F-SH-HN genome region of two other recent Italian isolates showed that they fall in the HK/FE/TW group. The predicted signal peptide of IT4524-2 F protein lacks the N-terminal first 10 aa that are present in the other five strains. Also, the F protein cleavage site of strain IT4524-2, (R) under bar EP (R) under bar down arrow L, has two dibasic aa (arginine, R) compared to the monobasic F protein cleavage site of PEP (R) under bar down arrow L. in the other strains. Reciprocal cross-hemagglutination inhibition (HI) assays using post-infection chicken sera indicated that strain IT4524-2 is antigenically related to the other APMV-6 strains, but with 4- to 8-fold lower HI tiers for the test sera between strain IT4524-2 and the other APMV-6 strains. Taken together, our results indicated that the APMV-6 strains represents a single serotype with two subgroups that differ substantially based on nt and aa sequences and can be distinguished by HI assay. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Xiao, Sa; Subbiah, Madhuri; Kumar, Sachin; Samal, Siba K.] Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
[De Nardi, Roberta; Terregino, Calogero] Ist Zooprofilatt Sperimentale Venezie, OIE FAO, Legnaro, PD, Italy.
[De Nardi, Roberta; Terregino, Calogero] Ist Zooprofilatt Sperimentale Venezie, Natl Reference Lab Newcastle Dis & Avian Influenz, Legnaro, PD, Italy.
[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
FU NIAID [N01A060009]; NIAID, NIH
FX We thank Drs. Ilaria Capua and Isabella Monne at IZSV, Italy for helpful
support and advice. We also thank Anandan Paldurai, Flavia Dias and
Dianel Rockemann for their excellent technical assistance and help.
"This research was supported by 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 mention of
trade names, commercial practices, or organizations imply endorsement by
the U.S. Government",
NR 47
TC 23
Z9 23
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1702
J9 VIRUS RES
JI Virus Res.
PD JUN
PY 2010
VL 150
IS 1-2
BP 61
EP 72
DI 10.1016/j.virusres.2010.02.015
PG 12
WC Virology
SC Virology
GA 598FU
UT WOS:000277821200009
PM 20206652
ER
PT J
AU Trask, SD
Guglielmi, KM
Patton, JT
AF Trask, Shane D.
Guglielmi, Kristen M.
Patton, John T.
TI Primed for Discovery: Atomic-Resolution Cryo-EM Structure of a Reovirus
Entry Intermediate
SO VIRUSES-BASEL
LA English
DT Article
DE aquareovirus; orthoreovirus; Reoviridae; electron cryomicroscopy;
nonenveloped virus; virus entry; myristoyl; autoproteolysis
ID MEMBRANE-PENETRATION PROTEIN; PUTATIVE AUTOCLEAVAGE; NONENVELOPED VIRUS;
CELL ENTRY; MU-1; PORES; TOMOGRAPHY; MICROSCOPY; PARTICLES; RELEASE
AB A recently solved structure of the aquareovirus virion (Zhang, X; Jin, L.; Fang, Q; Hui, W. H.; Zhou Z. H. 3.3 angstrom Cryo-EM Structure of a Nonenveloped Virus Reveals a Priming Mechanism for Cell Entry. Cell 2010, 141, 472-482 [1]) provides new insights into the order of entry events, as well as confirming and refining several aspects of the entry mechanism, for aquareovirus and the related orthoreovirus. In particular, the structure provides evidence of a defined order for the progressive proteolytic cleavages of myristoylated penetration protein VP5 that prime the virion for membrane penetration. These observations reinforce the concept that, much like enveloped viruses, nonenveloped virions often undergo priming events that lead to a meta-stable state, preparing the virus for membrane penetration under the appropriate circumstances. In addition, this and other recent studies highlight the increasing power of electron cryomicroscopy to analyze large, geometrically regular structures, such as icosahedral viruses, at atomic resolution.
C1 [Trask, Shane D.; Guglielmi, Kristen M.; Patton, John T.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Patton, JT (reprint author), NIAID, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM trasks@niaid.nih.gov; guglielmikm@niaid.nih.gov; jpatton@niaid.nih.gov
RI Patton, John/P-1390-2014
FU National Institute of Allergy and Infectious Diseases at the National
Institute of Health
FX We thank Sarah McDonald and Michelle Arnold for critical review of this
manuscript. The authors are supported by the Intramural Research Program
of the National Institute of Allergy and Infectious Diseases at the
National Institute of Health.
NR 19
TC 0
Z9 0
U1 0
U2 1
PU MDPI AG
PI BASEL
PA KANDERERSTRASSE 25, CH-4057 BASEL, SWITZERLAND
SN 1999-4915
J9 VIRUSES-BASEL
JI Viruses-Basel
PD JUN
PY 2010
VL 2
IS 6
BP 1340
EP 1346
DI 10.3390/v2061340
PG 7
WC Virology
SC Virology
GA 632HR
UT WOS:000280413800005
PM 21994683
ER
PT J
AU Jung, HH
Yang, ST
Sim, JY
Lee, S
Lee, JY
Kim, HH
Shin, SY
Kim, JI
AF Jung, Hyun Ho
Yang, Sung-Tae
Sim, Ji-Yeong
Lee, Seungkyu
Lee, Ju Yeon
Kim, Ha Hyung
Shin, Song Yub
Kim, Jae Il
TI Analysis of the solution structure of the human antibiotic peptide
dermcidin and its interaction with phospholipid vesicles
SO BMB REPORTS
LA English
DT Article
DE Amphipthic alpha-helical structure; Antimicrobial peptide;
Helix-hinge-helix motif; Nuclear magnetic resonance (NMR) spectroscopy;
Peptide-membrane interaction
ID HELICAL ANTIMICROBIAL PEPTIDES; NUCLEAR-MAGNETIC-RESONANCE; MODEL;
VERTEBRATES; MEMBRANES; PORES; HINGE; SWEAT
AB Dermcidin is a human antibiotic peptide that is secreted by the sweat glands and has no homology to other known antimicrobial peptides. As an initial step toward understanding dermcidin's mode of action at bacterial membranes, we used homonuclear and heteronuclear NMR to determine the conformation of the peptide in 50 h trifluoroethanol solution. We found that dermcidin adopts a flexible amphipathic alpha-helical structure with a helix-hinge-helix motif, which is a common molecular fold among antimicrobial peptides. Spin-down assays of dermcidin and several related peptides revealed that the affinity with which dermcidin binds to bacterial-mimetic membranes is primarily dependent on its amphipathic alpha-helical structure and its length (>30 residues); its negative net charge and acidic pl have little effect on binding. These findings suggest that the mode of action of dermcidin is similar to that of other membrane-targeting antimicrobial peptides, though the details of its antimicrobial action remain to be determined [BMB reports 2010; 43(5): 362-368]
C1 [Jung, Hyun Ho; Sim, Ji-Yeong; Lee, Seungkyu; Lee, Ju Yeon; Kim, Jae Il] Gwangju Inst Sci & Technol, Dept Life Sci, Kwangju, South Korea.
[Yang, Sung-Tae] NICHHD, Sect Membrane Biol, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA.
[Kim, Ha Hyung] Chung Ang Univ, Coll Pharm, Seoul 156756, South Korea.
[Shin, Song Yub] Chosun Univ, Grad Sch, Dept Biomat, Kwangju 501759, South Korea.
[Shin, Song Yub] Chosun Univ, Sch Med, Dept Cellular & Mol Med, Kwangju 501759, South Korea.
RP Kim, JI (reprint author), Gwangju Inst Sci & Technol, Dept Life Sci, Kwangju, South Korea.
EM jikim@gist.ac.kr
FU Brain Research Center of the 21st Century Frontier Research Program
[M103 KV010006-06K2201-00610]; Biolmaging Research Center; Ministry of
Health & Welfare, Republic of Korea
FX This study was supported by grants from the Brain Research Center of the
21st Century Frontier Research Program (M103 KV010006-06K2201-00610),
the Biolmaging Research Center at GIST, and the Korea Healthcare
Technology R&D Project, Ministry of Health & Welfare, Republic of Korea
(A080712).
NR 30
TC 9
Z9 10
U1 1
U2 6
PU KOREAN SOCIETY BIOCHEMISTRY & MOLECULAR BIOLOGY
PI SEOUL
PA KOREA SCIENCE & TECHNOLOGY CENTER, # 801, 635-4 , YEOKSAM-DONG,
KANGNAM-KU, SEOUL, 135-703, SOUTH KOREA
SN 1976-6696
J9 BMB REP
JI BMB Rep.
PD MAY 31
PY 2010
VL 43
IS 5
BP 362
EP 368
DI 10.5483/BMBRep.2010.43.5.362
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 603YR
UT WOS:000278244700010
PM 20510021
ER
PT J
AU Hirai, M
Minematsu, H
Hiramatsu, Y
Kitagawa, H
Otani, T
Iwashita, S
Kudoh, T
Chen, L
Li, Y
Okada, M
Salomon, DS
Igarashi, K
Chikuma, M
Seno, M
AF Hirai, M.
Minematsu, H.
Hiramatsu, Y.
Kitagawa, H.
Otani, T.
Iwashita, S.
Kudoh, T.
Chen, L.
Li, Y.
Okada, M.
Salomon, D. S.
Igarashi, K.
Chikuma, M.
Seno, M.
TI Novel and simple loading procedure of cisplatin into liposomes and
targeting tumor endothelial cells
SO INTERNATIONAL JOURNAL OF PHARMACEUTICS
LA English
DT Article
DE Cisplatin; Cis-diamminedinitratoplatinum (II); Liposome; E-selectin;
Sialyl Lewis(x)
ID LONG-CIRCULATING LIPOSOMES; STEALTH LIPOSOMES; THERAPEUTIC INDEX; MICE
BEARING; E-SELECTIN; PHASE-I; CANCER; PHARMACOKINETICS; ACCUMULATION;
CARCINOMA
AB Although intravenous administration of high levels of cisplatin (CDDP) are limited due to its severe side effects, efficient delivery of CDDP directly to the tumor should improve the therapeutic response while potentially by-passing significant side effects.
High loading of CDDP into liposomes is one technique that could be used as a potential drug delivery system. Since cis-diamminedinitratoplatinum (CDDP3) is highly soluble in water and converts to CDDP in the presence of chloride ions, we encapsulated CDDP3 into liposomes in the absence of chloride ions and supplemented chloride ions to prepare CDDP-encapsulated liposomes (CDDP-Lip) resulting in a significantly improved loading efficiency of COOP. We further conjugated the CDDP-Lip with Sialyl Lewis(X) (CDDP-SLX-Lip) because we previously demonstrated Sialyl Lewis(X) enhanced efficient accumulation of liposomes into tumors in vivo. CDDP-SLX-Lip treated mice showed a survival rate of 75% at 14 days even if a lethal level of CDDP was injected into mice. Loss of body weight was negligible and no histological abnormality was found in a variety of normal tissues. Accumulation of CDDP-SLX-Lip was about 6 times more than that of CDDP-Lip or CDDP. As the result, there was better antitumor activity of CDDP-SLX-Lip than that of CDDP-Lip with significantly less toxic effects in normal tissues. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Seno, M.] Okayama Univ, Grad Sch Nat Sci & Technol, Dept Med & Bioengn Sci, Lab Nanobiotechnol,Kita Ku, Okayama 7008530, Japan.
[Hirai, M.; Minematsu, H.; Hiramatsu, Y.; Kitagawa, H.; Otani, T.; Iwashita, S.; Igarashi, K.] Katayama Chem Ind Co LTD, R&D Div, Osaka 5620015, Japan.
[Salomon, D. S.] NCI, Tumor Growth Factor Sect, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Chikuma, M.] Osaka Univ Pharmaceut Sci, Osaka 569109, Japan.
RP Seno, M (reprint author), Okayama Univ, Grad Sch Nat Sci & Technol, Dept Med & Bioengn Sci, Lab Nanobiotechnol,Kita Ku, Room 361,Bldg ENG-6,3-1-1 Tsushima Naka, Okayama 7008530, Japan.
EM mseno@cc.okayama-u.ac.jp
RI SENO, Masaharu /B-2092-2011
OI SENO, Masaharu /0000-0001-8547-6259
FU Okayama University
FX We thank Prof. T. Ema (Okayama University) for his kind support and
helpful advises in measuring Pt content of CDDP by NMR and Prof. L. Fu
(Tianjin Medical School) for helpful discussions.
NR 38
TC 27
Z9 29
U1 5
U2 17
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-5173
J9 INT J PHARMACEUT
JI Int. J. Pharm.
PD MAY 31
PY 2010
VL 391
IS 1-2
BP 274
EP 283
DI 10.1016/j.ijpharm.2010.02.030
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 605JD
UT WOS:000278342900034
PM 20211714
ER
PT J
AU Rutkowski, DT
Hegde, RS
AF Rutkowski, D. Thomas
Hegde, Ramanujan S.
TI Regulation of basal cellular physiology by the homeostatic unfolded
protein response
SO JOURNAL OF CELL BIOLOGY
LA English
DT Review
ID ENDOPLASMIC-RETICULUM STRESS; TRANSCRIPTION FACTOR XBP1; BOX-BINDING
PROTEIN-1; ER STRESS; INSULIN-RESISTANCE; TRANSLATIONAL CONTROL;
GLUCOSE-HOMEOSTASIS; MESSENGER-RNA; IN-VIVO; B-CELLS
AB The extensive membrane network of the endoplasmic reticulum (ER) is physically juxtaposed to and functionally entwined with essentially all other cellular compartments. Therefore, the ER must sense diverse and constantly changing physiological inputs so it can adjust its numerous functions to maintain cellular homeostasis. A growing body of new work suggests that the unfolded protein response (UPR), traditionally charged with signaling protein misfolding stress from the ER, has been co-opted for the maintenance of basal cellular homeostasis. Thus, the UPR can be activated, and its output modulated, by signals far outside the realm of protein misfolding. These findings are revealing that the UPR causally contributes to disease not just by its role in protein folding but also through its broad influence on cellular physiology.
C1 [Rutkowski, D. Thomas] Univ Iowa, Dept Anat & Cell Biol, Carver Coll Med, Iowa City, IA 52242 USA.
[Hegde, Ramanujan S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
RP Rutkowski, DT (reprint author), Univ Iowa, Dept Anat & Cell Biol, Carver Coll Med, Iowa City, IA 52242 USA.
EM thomas-rutkowski@uiowa.edu; hegder@mail.nih.gov
OI Hegde, Ramanujan/0000-0001-8338-852X
FU National Institutes of Health [DK084058]; Carver Trust Medical Research
Initiative; Eunice Kennedy Shriver National Institute of Child Health
and Human Development at the National Institutes of Health
FX Work in the laboratory of D. T. Rutkowski is supported by the National
Institutes of Health (grant DK084058) and the Carver Trust Medical
Research Initiative. Work in the laboratory of R. S. Hegde is supported
by the Intramural Research Program of the Eunice Kennedy Shriver
National Institute of Child Health and Human Development at the National
Institutes of Health.
NR 104
TC 157
Z9 159
U1 4
U2 16
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0021-9525
J9 J CELL BIOL
JI J. Cell Biol.
PD MAY 31
PY 2010
VL 189
IS 5
BP 783
EP 794
DI 10.1083/jcb.201003138
PG 12
WC Cell Biology
SC Cell Biology
GA 602ZK
UT WOS:000278177500004
PM 20513765
ER
PT J
AU Akyurek, LM
Boehm, M
Olive, M
Zhou, AX
San, H
Nabel, EG
AF Akyuerek, Levent M.
Boehm, Manfred
Olive, Michelle
Zhou, Alex-Xianghua
San, Hong
Nabel, Elizabeth G.
TI Deficiency of cyclin-dependent kinase inhibitors p21(Cip1) and p27(Kip1)
accelerates atherogenesis in apolipoprotein E-deficient mice
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Proliferation; Atherosclerosis; Aorta; Neointima
ID MUSCLE-CELL-PROLIFERATION; RAT CAROTID-ARTERY; NEOINTIMAL HYPERPLASIA;
VASCULAR-DISEASE; ATHEROSCLEROSIS; ANGIOPLASTY; EXPRESSION; RESTENOSIS;
ANEURYSMS; PROTECTS
AB Cyclin-dependent kinase inhibitors, p21(Cip1) and p27(Kip1), are upregulated during vascular cell proliferation and negatively regulate growth of vascular cells. We hypothesized that absence of either p21(Cip1) or p21(Cip1) in apolipoprotein E (apoE)-deficiency may increase atherosclerotic plaque formation. Compared to apoE(-/-) aortae, both apoE(-/-)/p21(-/-) and apoE(-/-)/p27(-/-) aortae exhibited significantly more atherosclerotic plaque following a high-cholesterol regimen. This increase was particularly observed in the abdominal aortic regions. Deficiency of p27(Kip1) accelerated plaque formation significantly more than p21(-/-) in apoE(-/-) mice. This increased plaque formation was in parallel with increased intima/media area ratios. Deficiency of p21(Cip1) and p27(Kip1) accelerates atherogenesis in apoE(-/-) mice. These findings have significant implications for our understanding of the molecular basis of atherosclerosis associated with excessive proliferation of vascular cells. Published by Elsevier Inc.
C1 [Akyuerek, Levent M.; Boehm, Manfred; Olive, Michelle; San, Hong; Nabel, Elizabeth G.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Akyuerek, Levent M.; Boehm, Manfred; Olive, Michelle; San, Hong; Nabel, Elizabeth G.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Akyuerek, Levent M.; Zhou, Alex-Xianghua] Univ Gothenburg, Inst Biomed, Dept Med Biochem & Cell Biol, SE-40530 Gothenburg, Sweden.
RP Nabel, EG (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, 75 Francis St,PB408, Boston, MA 02115 USA.
EM enabel@partners.org
FU National Human Genome Research Institute, and National Heart, Lung, and
Blood Institute, National Institutes of Health, USA; Swedish Heart-Lung
Foundation; Swedish Research Council
FX We thank Xuan Qu for histological work, Olga Rivas and Robin
Schwartzbeck for animal breeding, and Diane C. Minerbi, David L. Katz,
and Jun Tashiro for helpful comments. This research was supported by the
Intramural Research Program of the National Human Genome Research
Institute, and National Heart, Lung, and Blood Institute, National
Institutes of Health, USA, and the Swedish Heart-Lung Foundation and the
Swedish Research Council.
NR 19
TC 13
Z9 16
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 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD MAY 28
PY 2010
VL 396
IS 2
BP 359
EP 363
DI 10.1016/j.bbrc.2010.04.097
PG 5
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 609LL
UT WOS:000278658000031
PM 20417618
ER
PT J
AU Kitajiri, S
Sakamoto, T
Belyantseva, IA
Goodyear, RJ
Stepanyan, R
Fujiwara, I
Bird, JE
Riazuddin, S
Riazuddin, S
Ahmed, ZM
Hinshaw, JE
Sellers, J
Bartles, JR
Hammer, JA
Richardson, GP
Griffith, AJ
Frolenkov, GI
Friedman, TB
AF Kitajiri, Shin-ichiro
Sakamoto, Takeshi
Belyantseva, Inna A.
Goodyear, Richard J.
Stepanyan, Ruben
Fujiwara, Ikuko
Bird, Jonathan E.
Riazuddin, Saima
Riazuddin, Sheikh
Ahmed, Zubair M.
Hinshaw, Jenny E.
Sellers, James
Bartles, James R.
Hammer, John A., III
Richardson, Guy P.
Griffith, Andrew J.
Frolenkov, Gregory I.
Friedman, Thomas B.
TI Actin-Bundling Protein TRIOBP Forms Resilient Rootlets of Hair Cell
Stereocilia Essential for Hearing
SO CELL
LA English
DT Article
ID F-ACTIN; BINDING-PROTEIN; CUTICULAR PLATE; BIRD COCHLEA; MYOSIN-XVA;
FILAMENTS; INNER; ELONGATION; MOUSE; ESPIN
AB Inner ear hair cells detect sound through deflection of mechanosensory stereocilia. Each stereocilium is supported by a paracrystalline array of parallel actin filaments that are packed more densely at the base, forming a rootlet extending into the cell body. The function of rootlets and the molecules responsible for their formation are unknown. We found that TRIOBP, a cytoskeleton-associated protein mutated in human hereditary deafness DFNB28, is localized to rootlets. In vitro, purified TRIOBP isoform 4 protein organizes actin filaments into uniquely dense bundles reminiscent of rootlets but distinct from bundles formed by espin, an actin crosslinker in stereocilia. We generated mutant Triobp mice (Triobp(Delta ex8/Delta ex8)) that are profoundly deaf. Stereocilia of Triobp(Delta ex8/Delta ex8) mice develop normally but fail to form rootlets and are easier to deflect and damage. Thus, F-actin bundling by TRIOBP provides durability and rigidity for normal mechanosensitivity of stereocilia and may contribute to resilient cytoskeletal structures elsewhere.
C1 [Kitajiri, Shin-ichiro; Belyantseva, Inna A.; Bird, Jonathan E.; Riazuddin, Saima; Ahmed, Zubair M.; Friedman, Thomas B.] Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, NIH, Rockville, MD 20850 USA.
[Griffith, Andrew J.] Natl Inst Deafness & Other Commun Disorders, Mol Biol & Genet Sect, NIH, Rockville, MD 20850 USA.
[Sakamoto, Takeshi; Sellers, James] NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA.
[Fujiwara, Ikuko; Hammer, John A., III] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Goodyear, Richard J.; Richardson, Guy P.] Univ Sussex, Sch Life Sci, Brighton BN1 9QG, E Sussex, England.
[Stepanyan, Ruben; Frolenkov, Gregory I.] Univ Kentucky, Dept Physiol, Lexington, KY 40536 USA.
[Riazuddin, Sheikh] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore 54700, Pakistan.
[Hinshaw, Jenny E.] NIDDKD, Struct Cell Biol Sect, NIH, Bethesda, MD 20892 USA.
[Bartles, James R.] Northwestern Univ, Feinberg Sch Med, Dept Cell & Mol Biol, Chicago, IL 60611 USA.
RP Friedman, TB (reprint author), Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, NIH, Rockville, MD 20850 USA.
EM friedman@nidcd.nih.gov
RI Fujiwara, Ikuko/H-5717-2016;
OI Fujiwara, Ikuko/0000-0002-9361-636X; Frolenkov,
Gregory/0000-0002-9810-5024; Bird, Jonathan/0000-0001-5531-8794
FU NIDCD/NIH [R01DC008861, R01DC009434, R01 DC004314]; Wellcome Trust
[071394/Z/03/Z]; HEC; MoST, Islamabad; NIDDK; NHLBI; NIDCD [Z01
DK060100, Z01 HL004232-08, Z01 DC 000064, Z01 DC000048]
FX The authors thank M. Ikeya for advice and vectors, M. Streuli for
mononclonal antiserum to TRIOBP-1/5, P. Belyantsev for drawings, and N.
Gavara, M. Barzik, R. Chadwick, J. Schultz, and D. Drayna for
discussions. This work was supported by NIDCD/NIH R01DC008861 and
R01DC009434 to G.I.F., R01 DC004314 to J.R.B., the Wellcome Trust grant
071394/Z/03/Z to G.P.R., the HEC and MoST, Islamabad to S.R., intramural
programs of NIDDK, NHLBI, and NIDCD Z01 DK060100 to J.E.H., Z01 DK060100
to J.A.H., Z01 HL004232-08 to J.S., Z01 DC 000064 to A.J.G., and Z01
DC000048 to T.B.
NR 37
TC 64
Z9 65
U1 1
U2 18
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD MAY 28
PY 2010
VL 141
IS 5
BP 786
EP 798
DI 10.1016/j.cell.2010.03.049
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 602IO
UT WOS:000278132900014
PM 20510926
ER
PT J
AU Hsu, NY
Ilnytska, O
Belov, G
Santiana, M
Chen, YH
Takvorian, PM
Pau, C
van der Schaar, H
Kaushik-Basu, N
Balla, T
Cameron, CE
Ehrenfeld, E
van Kuppeveld, FJM
Altan-Bonnet, N
AF Hsu, Nai-Yun
Ilnytska, Olha
Belov, Georgiy
Santiana, Marianita
Chen, Ying-Han
Takvorian, Peter M.
Pau, Cyrilla
van der Schaar, Hilde
Kaushik-Basu, Neerja
Balla, Tamas
Cameron, Craig E.
Ehrenfeld, Ellie
van Kuppeveld, Frank J. M.
Altan-Bonnet, Nihal
TI Viral Reorganization of the Secretory Pathway Generates Distinct
Organelles for RNA Replication
SO CELL
LA English
DT Article
ID HEPATITIS-C VIRUS; ENDOPLASMIC-RETICULUM; EXCHANGE FACTOR; POLIOVIRUS
RNA; INFECTIOUS VIRUS; COP-I; GOLGI; PROTEIN; TRANSPORT; DYNAMICS
AB Many RNA viruses remodel intracellular membranes to generate specialized sites for RNA replication. How membranes are remodeled and what properties make them conducive for replication are unknown. Here we show how RNA viruses can manipulate multiple components of the cellular secretory pathway to generate organelles specialized for replication that are distinct in protein and lipid composition from the host cell. Specific viral proteins modulate effector recruitment by Arf1 GTPase and its guanine nucleotide exchange factor GBF1, promoting preferential recruitment of phosphatidylinositol-4-kinase IIIb (PI4KIIIb) to membranes over coat proteins, yielding uncoated phosphatidylinositol-4-phosphate (PI4P) lipid-enriched organelles. The PI4P-rich lipid micro-environment is essential for both enteroviral and flaviviral RNA replication; PI4KIIIb inhibition interferes with this process; and enteroviral RNA polymerases specifically bind PI4P. These findings reveal how RNA viruses can selectively exploit specific elements of the host to form specialized organelles where cellular phosphoinositide lipids are key to regulating viral RNA replication.
C1 [Hsu, Nai-Yun; Ilnytska, Olha; Santiana, Marianita; Chen, Ying-Han; Takvorian, Peter M.; Pau, Cyrilla; Altan-Bonnet, Nihal] Rutgers State Univ, Dept Biol Sci, Newark, NJ 07102 USA.
[Belov, Georgiy; Ehrenfeld, Ellie] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[van der Schaar, Hilde; van Kuppeveld, Frank J. M.] Radboud Univ Nijmegen, Nijmegen Ctr Mol Life Sci, Med Ctr, Dept Med Microbiol, NL-6500 HB Nijmegen, Netherlands.
[Kaushik-Basu, Neerja] Univ Med & Dent Newark, Dept Biochem & Mol Biol, Newark, NJ 07101 USA.
[Balla, Tamas] NICHD, Sect Mol Signal Transduct, NIH, Bethesda, MD 20892 USA.
[Cameron, Craig E.] Penn State Univ, Dept Biochem & Mol Biol, State Coll, PA 16803 USA.
RP Altan-Bonnet, N (reprint author), Rutgers State Univ, Dept Biol Sci, Newark, NJ 07102 USA.
EM nabonnet@andromeda.rutgers.edu
RI Belov, George/B-4625-2008;
OI Belov, George/0000-0002-0892-1731; Balla, Tamas/0000-0002-9077-3335
FU NIH (NIAID) [AI053531]; NIH(NICHD); Netherlands Organisation for
Scientific Research [NWO-VIDI-917.46.306, NWO-ECHO-700.57.001]; NIDDK,
NIH [DK06687]; National Science Foundation [MCB0822058]; Busch
Foundation [649117]
FX We thank J. Lippincott-Schwartz, S. M. Simon, K. Hirschberg, T. Ward, R.
Hegde, R. Collins, J. Arnold, and G. Altan-Bonnet for insightful
discussions. E.E. and G.B. were supported by the Intramural Research
Program of the NIH (NIAID); T.B. was supported by the Intramural
Research Program of the NIH(NICHD); C.E.C. was supported by grant
AI053531 (NIAID, NIH); F.J.M.v.K. was supported by Netherlands
Organisation for Scientific Research (NWO-VIDI-917.46.306,
NWO-ECHO-700.57.001); N.K.B. was supported by grant DK06687 (NIDDK,
NIH); and N.A.-B. was supported with grant MCB0822058 from the National
Science Foundation and grant 649117 from the Busch Foundation.
NR 51
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PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD MAY 28
PY 2010
VL 141
IS 5
BP 799
EP 811
DI 10.1016/j.cell.2010.03.050
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 602IO
UT WOS:000278132900015
PM 20510927
ER
PT J
AU Li, Z
Jo, J
Jia, JM
Lo, SC
Whitcomb, DJ
Jiao, S
Cho, K
Sheng, M
AF Li, Zheng
Jo, Jihoon
Jia, Jie-Min
Lo, Shih-Ching
Whitcomb, Daniel J.
Jiao, Song
Cho, Kwangwook
Sheng, Morgan
TI Caspase-3 Activation via Mitochondria Is Required for Long-Term
Depression and AMPA Receptor Internalization
SO CELL
LA English
DT Article
ID SYNAPTIC PLASTICITY; CELL-DEATH; INDUCED APOPTOSIS; STRUCTURAL BASIS;
CLEAVAGE; LTD; INHIBITION; FAMILY; XIAP; HIPPOCAMPUS
AB NMDA receptor-dependent synaptic modifications, such as long-term potentiation (LTP) and long-term depression (LTD), are essential for brain development and function. LTD occurs mainly by the removal of AMPA receptors from the postsynaptic membrane, but the underlying molecular mechanisms remain unclear. Here, we show that activation of caspase-3 via mitochondria is required for LTD and AMPA receptor internalization in hippocampal neurons. LTD and AMPA receptor internalization are blocked by peptide inhibitors of caspase-3 and -9. In hippocampal slices from caspase-3 knockout mice, LTD is abolished whereas LTP remains normal. LTD is also prevented by overexpression of the anti-apoptotic proteins XIAP or Bcl-xL, and by a mutant Akt1 protein that is resistant to caspase-3 proteolysis. NMDA receptor stimulation that induces LTD transiently activates caspase-3 in dendrites, without causing cell death. These data indicate an unexpected causal link between the molecular mechanisms of apoptosis and LTD.
C1 [Li, Zheng; Sheng, Morgan] MIT, Picower Inst Learning & Memory, Cambridge, MA 02139 USA.
[Jo, Jihoon; Whitcomb, Daniel J.; Cho, Kwangwook] Univ Bristol, Fac Med & Dent, Henry Wellcome LINE & MRC Ctr Synapt Plast, Bristol BS1 3NY, Avon, England.
[Li, Zheng; Jia, Jie-Min; Jiao, Song] NIMH, Unit Synapse Dev & Plast, Gene Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA.
[Lo, Shih-Ching; Sheng, Morgan] Genentech Inc, Dept Neurosci, San Francisco, CA 94080 USA.
RP Li, Z (reprint author), MIT, Picower Inst Learning & Memory, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM lizheng2@mail.nih.gov; Kei.Cho@bristol.ac.uk
RI Jia, Jie-Min/O-1150-2013; Li, Zheng/I-8016-2014; Jiao, Song/L-2803-2015;
OI Jia, Jie-Min/0000-0001-8446-3819; Li, Zheng/0000-0002-2978-2531; Jiao,
Song/0000-0003-0496-6454; Whitcomb, Daniel/0000-0003-2703-1643
FU NIH [F32-NS046126]; NIMH; BBSRC; Alzheimer's Research Trust UK
FX We thank Colin S. Duckett and Azad Bonni for plasmid constructs. M. S.
was Investigator of the Howard Hughes Medical Institute. Z. L. was a
recipient of NIH fellowship (F32-NS046126) and is supported by NIMH
Division of Intramural Research Programs. This work is supported by
BBSRC (K.C.) Alzheimer's Research Trust UK (K.C.), and the Intramural
Program of the NIH, NIMH (Z.L., J.J. and S.J.). M.S. and S.-C.L. are
employees of Genentech Inc, a member of the Roche Group.
NR 56
TC 237
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U1 5
U2 38
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD MAY 28
PY 2010
VL 141
IS 5
BP 859
EP 871
DI 10.1016/j.cell.2010.03.053
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 602IO
UT WOS:000278132900020
PM 20510932
ER
PT J
AU Pommier, Y
Leo, E
Zhang, HL
Marchand, C
AF Pommier, Yves
Leo, Elisabetta
Zhang, HongLiang
Marchand, Christophe
TI DNA Topoisomerases and Their Poisoning by Anticancer and Antibacterial
Drugs
SO CHEMISTRY & BIOLOGY
LA English
DT Review
ID POSITIVELY SUPERCOILED DNA; ACUTE MYELOID-LEUKEMIA; ESCHERICHIA-COLI; I
INHIBITORS; COVALENT COMPLEXES; CYTO-TOXICITY; CAMPTOTHECIN RESISTANCE;
CHEMOTHERAPEUTIC-AGENTS; ANTITUMOR-ACTIVITY; REPLICATION FORKS
AB DNA topoisomerases are the targets of important anticancer and antibacterial drugs. Camptothecins and novel noncamptothecins in clinical development (indenoisoquinolines and ARC-111) target eukaryotic type IB topoisomerases (Top1), whereas human type HA topoisomerases (Top2 alpha and Top2 beta) are the targets of the widely used anticancer agents etoposide, anthracyclines (doxorubicin, daunorubicin), and mitoxantrone. Bacterial type II topoisomerases (gyrase and Topo IV) are the targets of quinolones and aminocoumarin antibiotics. This review focuses on the molecular and biochemical characteristics of topoisomerases and their inhibitors. We also discuss the common mechanism of action of topoisomerase poisons by interfacial inhibition and trapping of topoisomerase cleavage complexes.
C1 [Pommier, Yves; Leo, Elisabetta; Zhang, HongLiang; Marchand, Christophe] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM pommier@nih.gov
FU National Cancer Institute, National Institutes of Health
FX Our studies have been supported by the Center for Cancer Research,
Intramural Program of the National Cancer Institute, National Institutes
of Health. We wish to thank Kurt Kohn as outstanding mentor and
colleague, and Elie Pommier for help with chemical structures.
NR 116
TC 542
Z9 554
U1 25
U2 152
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-5521
J9 CHEM BIOL
JI Chem. Biol.
PD MAY 28
PY 2010
VL 17
IS 5
BP 421
EP 433
DI 10.1016/j.chembiol.2010.04.012
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 611TE
UT WOS:000278845000005
PM 20534341
ER
PT J
AU Shevach, EM
AF Shevach, Ethan M.
TI TGF-beta to the Rescue
SO IMMUNITY
LA English
DT Editorial Material
ID REGULATORY T-CELLS
AB Is transforming growth factor-beta (TGF-beta) required for induction of the transcription factor Foxp3 in developing thymocytes? Ouyang et al. (2010) demonstrate that TGF-beta in the thymus prevents deletion of Foxp3(+) regulatory T cells.
C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Shevach, EM (reprint author), NIAID, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM eshevach@niaid.nih.gov
NR 7
TC 4
Z9 4
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD MAY 28
PY 2010
VL 32
IS 5
BP 585
EP 587
DI 10.1016/j.immuni.2010.04.014
PG 3
WC Immunology
SC Immunology
GA 604LM
UT WOS:000278280500003
PM 20510867
ER
PT J
AU Murphy, PM
AF Murphy, Philip M.
TI Double Duty for CCL21 in Dendritic Cell Trafficking
SO IMMUNITY
LA English
DT Editorial Material
ID MIGRATION
AB Mechanisms controlling leukocyte adhesion, propulsion and directional migration have not been fully integrated. In this issue of Immunity, Schumann et al. (2010) propose that DCs swarm to T cell zones using immobilized CCL21 for adhesive random migration and soluble CCL21 for steering.
C1 NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
RP Murphy, PM (reprint author), NIAID, Lab Mol Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM pmm@nih.gov
FU Intramural NIH HHS [ZIA AI000615-21]
NR 9
TC 5
Z9 5
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD MAY 28
PY 2010
VL 32
IS 5
BP 590
EP 592
DI 10.1016/j.immuni.2010.05.004
PG 3
WC Immunology
SC Immunology
GA 604LM
UT WOS:000278280500005
PM 20510869
ER
PT J
AU Durant, L
Watford, WT
Ramos, HL
Laurence, A
Vahedi, G
Wei, L
Takahashi, H
Sun, HW
Kanno, Y
Powrie, F
O'Shea, JJ
AF Durant, Lydia
Watford, Wendy T.
Ramos, Haydee L.
Laurence, Arian
Vahedi, Golnez
Wei, Lai
Takahashi, Hayato
Sun, Hong-Wei
Kanno, Yuka
Powrie, Fiona
O'Shea, John J.
TI Diverse Targets of the Transcription Factor STAT3 Contribute to T Cell
Pathogenicity and Homeostasis
SO IMMUNITY
LA English
DT Article
ID INFLAMMATORY-BOWEL-DISEASE; HYPER-IGE SYNDROME; GENOME-WIDE ASSOCIATION;
IN-VIVO; INTESTINAL INFLAMMATION; HELPER-CELLS; T-H-17 CELLS; TH17
CELLS; ROR-GAMMA; DIFFERENTIATION
AB STAT3, an essential transcription factor with pleiotropic functions, plays critical roles in the pathogenesis of autoimmunity. Despite recent data linking STAT3 with inflammatory bowel disease, exactly how it contributes to chronic intestinal inflammation is not known. Using a T cell transfer model of colitis, we found that STAT3 expression in T cells was essential for the induction of both colitis and systemic inflammation. STAT3 was critical in modulating the balance of T helper 17 (Th17) and regulatory T (Treg) cells, as well as in promoting CD4(+) T cell proliferation. We used chromatin immunoprecipitation and massive parallel sequencing (ChIP-Seq) to define the genome-wide targets of STAT3 in CD4(+) T cells. We found that STAT3 bound to multiple genes involved in Th17 cell differentiation, cell activation, proliferation, and survival, regulating both expression and epigenetic modifications. Thus, STAT3 orchestrates multiple critical aspects of T cell function in inflammation and homeostasis.
C1 [Durant, Lydia; Watford, Wendy T.; Ramos, Haydee L.; Laurence, Arian; Vahedi, Golnez; Wei, Lai; Takahashi, Hayato; Kanno, Yuka; O'Shea, John J.] NIAMSD, Lymphocyte Cell Biol Sect, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA.
[Durant, Lydia; Powrie, Fiona] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England.
[Durant, Lydia; Powrie, Fiona] Univ Oxford, John Radcliffe Hosp, Translat Gastroenterol Unit, Nuffield Dept Clin Med, Oxford OX3 9DU, England.
[Sun, Hong-Wei] NIAMSD, Biodata Min & Discovery Sect, Bethesda, MD 20892 USA.
RP Durant, L (reprint author), NIAMSD, Lymphocyte Cell Biol Sect, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA.
EM durantl@mail.nih.gov
RI Laurence, Arian/A-8770-2009; Kanno, Yuka/B-5802-2013; Wei,
Lai/D-1088-2014;
OI Laurence, Arian/0000-0003-0942-8292; Kanno, Yuka/0000-0001-5668-9319
FU Intramural Research Program at NIAMS; National Institutes of Health [1
K22 AR53953-01]; Wellcome Trust
FX We thank J. Simone, J.Lay, K. Zaal, and the NIAMS LACU Staff for their
assistance. We thank P. Ahern, M. Asquith, and A. Izcue for advice and
critical reading of the manuscript. This research was funded by the
Intramural Research Program at NIAMS. W.T.W. is supported by National
Institutes of Health grant #1 K22 AR53953-01. F.P. is supported by
funding from the Wellcome Trust.
NR 52
TC 244
Z9 257
U1 0
U2 25
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD MAY 28
PY 2010
VL 32
IS 5
BP 605
EP 615
DI 10.1016/j.immuni.2010.05.003
PG 11
WC Immunology
SC Immunology
GA 604LM
UT WOS:000278280500007
PM 20493732
ER
PT J
AU Ekundayo, OJ
Adamopoulos, C
Ahmed, MI
Pitt, B
Young, JB
Fleg, JL
Love, TE
Sui, XM
Perry, GJ
Siscovick, DS
Bakris, G
Ahmed, A
AF Ekundayo, O. James
Adamopoulos, Chris
Ahmed, Mustafa I.
Pitt, Bertram
Young, James B.
Fleg, Jerome L.
Love, Thomas E.
Sui, Xuemei
Perry, Gilbert J.
Siscovick, David S.
Bakris, George
Ahmed, Ali
TI Oral potassium supplement use and outcomes in chronic heart failure: A
propensity-matched study
SO INTERNATIONAL JOURNAL OF CARDIOLOGY
LA English
DT Article
DE Heart failure; Potassium supplement; Mortality; Hospitalization;
Propensity score
ID SERUM POTASSIUM; MYOCARDIAL-INFARCTION; SCORE METHODS; DIG TRIAL;
MORTALITY; MORBIDITY; HYPERTENSION; APPETITE; SHEEP; BIAS
AB Background: Hypokalemia is common in heart failure (HF) and is associated with increased mortality. Potassium supplements are commonly used to treat hypokalemia and maintain normokalemia. However, their long-term effects on outcomes in chronic HF are unknown. We used a public-use copy of the Digitalis Investigation Group (DIG) trial dataset to determine the associations of potassium supplement use with outcomes using a propensity-matched design.
Methods: Of the 7788 DIG participants with chronic HF, 2199 were using oral potassium supplements at baseline. We estimated propensity scores for potassium supplement use for each patient and used them to match 2131 pairs of patients receiving and not receiving potassium supplements. Matched Cox regression models were used to estimate associations of potassium supplement use with mortality and hospitalization during 40 months of median follow-up.
Results: All-cause mortality occurred in 818 (rate, 1327/10,000 person-years) and 802 (rate, 1313/10,000 person-years) patients respectively receiving and not receiving potassium supplements (hazard ratio {HR} when potassium supplement use was compared with nonuse, 1.05; 95% confidence interval {CI}, 0.94-1.18; P=0.390). All-cause hospitalizations occurred in 1516 (rate, 4777/10,000 person-years) and 1445 (rate, 4120/10,000 person-years) patients respectively receiving and not receiving potassium supplements (HR, 1.15; 95% CI, 1.05-1.26; P-0.004). HRs (95% CI) for hospitalizations due to cardiovascular causes and worsening HF were respectively 1.19 (95% CI, 1.081.32; P=0.001) and 1.27 (1.12-1.43; P<0.0001).
Conclusion: The use of potassium supplements in chronic HF was not associated with mortality. However, their use was associated with increased hospitalization due to cardiovascular causes and progressive HF. Published by Elsevier Ireland Ltd.
C1 [Ekundayo, O. James; Ahmed, Mustafa I.; Perry, Gilbert J.; Ahmed, Ali] Univ Alabama, Birmingham, AL 35294 USA.
[Adamopoulos, Chris] Papageorgiou Gen Hosp, Thessaloniki, Greece.
[Pitt, Bertram] Univ Michigan, Ann Arbor, MI 48109 USA.
[Young, James B.] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
[Fleg, Jerome L.] NHLBI, Bethesda, MD 20892 USA.
[Love, Thomas E.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Sui, Xuemei] Univ S Carolina, Columbia, SC 29208 USA.
[Perry, Gilbert J.; Ahmed, Ali] VA Med Ctr, Birmingham, AL USA.
[Siscovick, David S.] Univ Washington, Seattle, WA 98195 USA.
[Bakris, George] Univ Chicago, Chicago, IL 60637 USA.
RP Ahmed, A (reprint author), Univ Alabama, 1530 3rd Ave S,CH 19,Ste 219, Birmingham, AL 35294 USA.
EM aahmed@uab.edu
FU NHLBI
FX "The Digitalis Investigation Group ( DIG) study was conducted and
supported by the NHLBI in collaboration with the DIG Investigators. This
manuscript was prepared using a limited access dataset obtained by the
NHLBI and does not necessarily reflect the opinions or views of the DIG
Study or the NHLBI."
NR 31
TC 20
Z9 21
U1 0
U2 3
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0167-5273
J9 INT J CARDIOL
JI Int. J. Cardiol.
PD MAY 28
PY 2010
VL 141
IS 2
BP 167
EP 174
DI 10.1016/j.ijcard.2008.11.195
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 597AI
UT WOS:000277727200008
PM 19135741
ER
PT J
AU Garcia-Diaz, M
Murray, MS
Kunkel, TA
Chou, KM
AF Garcia-Diaz, Miguel
Murray, Michael S.
Kunkel, Thomas A.
Chou, Kai-ming
TI Interaction between DNA Polymerase lambda and Anticancer Nucleoside
Analogs
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID REPAIR; GEMCITABINE; CELLS; FIBROBLASTS; METABOLISM; MECHANISM;
SOFTWARE; EXTRACTS; CANCER
AB The anticancer activity of cytarabine (AraC) and gemcitabine (dFdC) is thought to result from chain termination after incorporation into DNA. To investigate their incorporation into DNA at atomic level resolution, we present crystal structures of human DNA polymerase lambda (Pol lambda) bound to gapped DNA and containing either AraC or dFdC paired opposite template dG. These structures reveal that AraC and dFdC can bind within the nascent base pair binding pocket of Pol lambda. Although the conformation of the ribose of AraCTP is similar to that of normal dCTP, the conformation of dFdCTP is significantly different. Consistent with these structures, Pol lambda efficiently incorporates AraCTP but not dFdCTP. The data are consistent with the possibility that Pol lambda could modulate the cytotoxic effect of AraC.
C1 [Chou, Kai-ming] Indiana Univ, Sch Med, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 USA.
NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
NIEHS, Mol Genet Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Chou, KM (reprint author), Indiana Univ, Sch Med, Dept Pharmacol & Toxicol, 635 Barnhill Dr,MS 552, Indianapolis, IN 46202 USA.
EM chouk@iupui.edu
FU National Institutes of Health (NIH) [RO1 CA112446]; NIH, NIEHS [Z01
ES065070]
FX This work was supported, in whole or in part, by National Institutes of
Health (NIH) Grant RO1 CA112446 (to K.-m.C.) and by NIH, NIEHS, Division
of Intramural Research Project Z01 ES065070 (to T.A.K.).
NR 37
TC 6
Z9 6
U1 0
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAY 28
PY 2010
VL 285
IS 22
BP 16874
EP 16879
DI 10.1074/jbc.M109.094391
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 600JS
UT WOS:000277982600051
PM 20348107
ER
PT J
AU Playford, MP
Nurminen, E
Pentikainen, OT
Milgram, SL
Hartwig, JH
Stossel, TP
Nakamura, F
AF Playford, Martin P.
Nurminen, Elisa
Pentikainen, Olli T.
Milgram, Sharon L.
Hartwig, John H.
Stossel, Thomas P.
Nakamura, Fumihiko
TI Cystic Fibrosis Transmembrane Conductance Regulator Interacts with
Multiple Immunoglobulin Domains of Filamin A
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID STRUCTURAL BASIS; CHLORIDE CHANNELS; PLASMA-MEMBRANE; MOLECULAR-BASIS;
CFTR; BINDING; CELLS; CYTOSKELETON; COMPETITION; EXPRESSION
AB Mutations of the chloride channel cystic fibrosis transmembrane conductance regulator (CFTR) that impair its apical localization and function cause cystic fibrosis. A previous report has shown that filamin A (FLNa), an actin-cross-linking and -scaffolding protein, interacts directly with the cytoplasmic N terminus of CFTR and that this interaction is necessary for stability and confinement of the channel to apical membranes. Here, we report that the CFTR N terminus has sequence similarity to known FLNa-binding partner-binding sites. FLNa has 24 Ig (IgFLNa) repeats, and a CFTR peptide pulled down repeats 9, 12, 17, 19, 21, and 23, which share sequence similarity yet differ from the other FLNa Ig domains. Using known structures of IgFLNa.partner complexes as templates, we generated in silico models of IgFLNa.CFTR peptide complexes. Point and deletion mutants of IgFLNa and CFTR informed by the models, including disease-causing mutations L15P and W19C, disrupted the binding interaction. The model predicted that a P5L CFTR mutation should not affect binding, but a synthetic P5L mutant peptide had reduced solubility, suggesting a different disease-causing mechanism. Taken together with the fact that FLNa dimers are elongated (similar to 160 nm) strands, whereas CFTR is compact (6 similar to 8 nm), we propose that a single FLNa molecule can scaffold multiple CFTR partners. Unlike previously defined dimeric FLNa.partner complexes, the FLNa-monomeric CFTR interaction is relatively weak, presumptively facilitating dynamic clustering of CFTR at cell membranes. Finally, we show that deletion of all CFTR interacting domains from FLNa suppresses the surface expression of CFTR on baby hamster kidney cells.
C1 [Hartwig, John H.; Stossel, Thomas P.; Nakamura, Fumihiko] Harvard Univ, Brigham & Womens Hosp, Sch Med, Translat Med Div,Dept Med, Boston, MA 02115 USA.
[Nurminen, Elisa; Pentikainen, Olli T.] Univ Jyvaskyla, Dept Biol & Environm Sci, FI-40014 Jyvaskyla, Finland.
[Nurminen, Elisa; Pentikainen, Olli T.] Univ Jyvaskyla, Nanosci Ctr, FI-40014 Jyvaskyla, Finland.
[Playford, Martin P.; Milgram, Sharon L.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Nakamura, F (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Translat Med Div,Dept Med, Boston, MA 02115 USA.
EM fnakamura@rics.bwh.harvard.edu
RI Pentikainen, Olli/E-1980-2012; Nakamura, Fumihiko/N-5476-2016
OI Pentikainen, Olli/0000-0001-7188-4016;
FU National Institutes of Health [HL-19429, HL-56252]; HUSEC Seed Fund for
Interdisciplinary Science; Sigrid Juselius Foundation; University of
Jyvaskyla; Finnish IT Center for Science Computational Grant [jyy2516]
FX This work was supported by National Institutes of Health Grants HL-19429
(to T. P. S.) and HL-56252 (to J. H. H.). This work was also supported
by the HUSEC Seed Fund for Interdisciplinary Science (T. P. S. and F.
N.), the Sigrid Juselius Foundation (O. T. P.), the University of
Jyvaskyla (E. N.), and the Finnish IT Center for Science Computational
Grant for Project jyy2516 (to O. T. P.).
NR 32
TC 17
Z9 17
U1 1
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 MAY 28
PY 2010
VL 285
IS 22
BP 17156
EP 17165
DI 10.1074/jbc.M109.080523
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 600JS
UT WOS:000277982600078
PM 20351098
ER
PT J
AU Hashimoto, K
Madej, T
Bryant, SH
Panchenko, AR
AF Hashimoto, Kosuke
Madej, Thomas
Bryant, Stephen H.
Panchenko, Anna R.
TI Functional States of Homooligomers: Insights from the Evolution of
Glycosyltransferases
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE glycosyltransferase; homodimer; homooligomerization; interface; protein
structural evolution
ID PROTEIN-GLYCAN INTERACTIONS; GLYCOGEN-PHOSPHORYLASE; DOMAIN
INTERACTIONS; HEPARAN-SULFATE; BIOSYNTHESIS; SIMILARITIES; DIMERIZATION;
MECHANISMS; SEQUENCES; SYNTHASE
AB Glycosylation is an important aspect of epigenetic regulation. Glycosyltransferase is a key enzyme in the biosynthesis of glycans, which glycosylates more than half of all proteins in eukaryotes and is involved in a wide range of biological processes. It has been suggested previously that homooligomerization in glycosyltransferases and other proteins might be crucial for their function. In this study, we explore functional homooligomeric states of glycosyltransferases in various organisms, trace their evolution, and perform comparative analyses to find structural features that can mediate or disrupt the formation of different homooligomers. First, we make a structure-based classification of the diverse superfamily of glycosyltransferases and confirm that the majority of the structures are indeed clustered into the GT-A or GT-B folds. We find that homooligomeric glycosyltransferases appear to be as ancient as monomeric glycosyltransferases and go back in evolution to the last universal common ancestor (LUCA). Moreover, we show that interface residues have significant bias to be gapped out or unaligned in the monomers, implying that they might represent features crucial for oligomer formation. Structural analysis of these features reveals that the majority of them represent loops, terminal regions, and helices, indicating that these secondary-structure elements mediate the formation of glycosyltransferases homooligomers and directly contribute to the specific binding. We also observe relatively short protein regions that disrupt the homodimer interactions, although such cases are rare. These results suggest that relatively small structural changes in the nonconserved regions may contribute to the formation of different functional oligomeric states and might be important in regulation of enzyme activity through homooligomerization. Published by Elsevier Ltd.
C1 [Hashimoto, Kosuke; Madej, Thomas; Bryant, Stephen H.; Panchenko, Anna R.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Panchenko, AR (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, 8600 Rockville Pike,Bldg 38A 8S814, Bethesda, MD 20894 USA.
EM panch@ncbi.nlm.nih.gov
FU National Institutes of Health/DHHS; Japan Society for the Promotion of
Science
FX We thank Yuri Wolf for careful reading of the manuscript. This work was
supported by National Institutes of Health/DHHS (Intramural Research
program of the National Library of Medicine). K.H. was supported by a
Research Fellowship from the Japan Society for the Promotion of Science.
NR 53
TC 21
Z9 22
U1 0
U2 2
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 MAY 28
PY 2010
VL 399
IS 1
BP 196
EP 206
DI 10.1016/j.jmb.2010.03.059
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 610ZL
UT WOS:000278779900016
PM 20381499
ER
PT J
AU Elliott, KS
Zeggini, E
McCarthy, MI
Gudmundsson, J
Sulem, P
Stacey, SN
Thorlacius, S
Amundadottir, L
Gronberg, H
Xu, JF
Gaborieau, V
Eeles, RA
Neal, DE
Donovan, JL
Hamdy, FC
Muir, K
Hwang, SJ
Spitz, MR
Zanke, B
Carvajal-Carmona, L
Brown, KM
Hayward, NK
Macgregor, S
Tomlinson, IPM
Lemire, M
Amos, CI
Murabito, JM
Isaacs, WB
Easton, DF
Brennan, P
Barkardottir, RB
Gudbjartsson, DF
Rafnar, T
Hunter, DJ
Chanock, SJ
Stefansson, K
Ioannidis, JPA
AF Elliott, Katherine S.
Zeggini, Eleftheria
McCarthy, Mark I.
Gudmundsson, Julius
Sulem, Patrick
Stacey, Simon N.
Thorlacius, Steinunn
Amundadottir, Laufey
Groenberg, Henrik
Xu, Jianfeng
Gaborieau, Valerie
Eeles, Rosalind A.
Neal, David E.
Donovan, Jenny L.
Hamdy, Freddie C.
Muir, Kenneth
Hwang, Shih-Jen
Spitz, Margaret R.
Zanke, Brent
Carvajal-Carmona, Luis
Brown, Kevin M.
Hayward, Nicholas K.
Macgregor, Stuart
Tomlinson, Ian P. M.
Lemire, Mathieu
Amos, Christopher I.
Murabito, Joanne M.
Isaacs, William B.
Easton, Douglas F.
Brennan, Paul
Barkardottir, Rosa B.
Gudbjartsson, Daniel F.
Rafnar, Thorunn
Hunter, David J.
Chanock, Stephen J.
Stefansson, Kari
Ioannidis, John P. A.
CA Australian Melanoma Family Study I
PanScan Consortium
TI Evaluation of Association of HNF1B Variants with Diverse Cancers:
Collaborative Analysis of Data from 19 Genome-Wide Association Studies
SO PLOS ONE
LA English
DT Article
ID PROSTATE-CANCER; DIABETES-MELLITUS; SUSCEPTIBILITY LOCUS; BREAST-CANCER;
LUNG-CANCER; RISK LOCI; SEQUENCE VARIANTS; COMMON VARIANTS; GENE;
METAANALYSIS
AB Background: Genome-wide association studies have found type 2 diabetes-associated variants in the HNF1B gene to exhibit reciprocal associations with prostate cancer risk. We aimed to identify whether these variants may have an effect on cancer risk in general versus a specific effect on prostate cancer only.
Methodology/Principal Findings: In a collaborative analysis, we collected data from GWAS of cancer phenotypes for the frequently reported variants of HNF1B, rs4430796 and rs7501939, which are in linkage disequilibrium (r(2) = 0.76, HapMap CEU). Overall, the analysis included 16 datasets on rs4430796 with 19,640 cancer cases and 21,929 controls; and 21 datasets on rs7501939 with 26,923 cases and 49,085 controls. Malignancies other than prostate cancer included colorectal, breast, lung and pancreatic cancers, and melanoma. Meta-analysis showed large between-dataset heterogeneity that was driven by different effects in prostate cancer and other cancers. The per-T2D-risk-allele odds ratios (95% confidence intervals) for rs4430796 were 0.79 (0.76, 0.83)] per G allele for prostate cancer (p < 10(-15) for both); and 1.03 (0.99, 1.07) for all other cancers. Similarly for rs7501939 the per-T2D-risk-allele odds ratios (95% confidence intervals) were 0.80 (0.77, 0.83) per T allele for prostate cancer (p < 10(-15) for both); and 1.00 (0.97, 1.04) for all other cancers. No malignancy other than prostate cancer had a nominally statistically significant association.
Conclusions/Significance: The examined HNF1B variants have a highly specific effect on prostate cancer risk with no apparent association with any of the other studied cancer types.
C1 [Elliott, Katherine S.; Zeggini, Eleftheria; McCarthy, Mark I.; Carvajal-Carmona, Luis; Tomlinson, Ian P. M.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Zeggini, Eleftheria] Univ Cambridge, Wellcome Trust Sanger Inst, Cambridge, England.
[McCarthy, Mark I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
[Gudmundsson, Julius; Sulem, Patrick; Stacey, Simon N.; Thorlacius, Steinunn; Gudbjartsson, Daniel F.; Rafnar, Thorunn; Stefansson, Kari] deCODE Genet, Reykjavik, Iceland.
[Amundadottir, Laufey; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Groenberg, Henrik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Xu, Jianfeng] Wake Forest Univ, Bowman Gray Sch Med, Ctr Canc Genom, Winston Salem, NC USA.
[Xu, Jianfeng] Wake Forest Univ, Bowman Gray Sch Med, Ctr Human Genom, Winston Salem, NC USA.
[Gaborieau, Valerie] IARC, Genet Epidemiol Grp, Lyon, France.
[Eeles, Rosalind A.] Inst Canc Res, Oncogenet Team, Sutton, Surrey, England.
[Neal, David E.] Univ Cambridge, Dept Oncol, Cambridge, England.
[Donovan, Jenny L.] Univ Bristol, Dept Social Med, Bristol, Avon, England.
[Hamdy, Freddie C.] Univ Oxford, Nuffield Dept Surg, Oxford, England.
[Muir, Kenneth] Univ Warwick, Hlth Sci Res Inst, Coventry CV4 7AL, W Midlands, England.
[Hwang, Shih-Jen] NHLBI, Framingham Study, Bethesda, MD 20892 USA.
[Spitz, Margaret R.; Amos, Christopher I.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Zanke, Brent; Lemire, Mathieu] Ontario Inst Canc Res, MaRS Ctr, Toronto, ON, Canada.
[Zanke, Brent] Univ Ottawa, Ottawa Hlth Res Inst, Ottawa, ON, Canada.
[Brown, Kevin M.] Translat Genom Res Inst, Integrated Canc Genom Div, Phoenix, AZ USA.
[Hayward, Nicholas K.; Macgregor, Stuart] Royal Brisbane Hosp, Queensland Inst Med Res, Brisbane, Qld 4029, Australia.
[Murabito, Joanne M.] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA.
[Isaacs, William B.] Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA.
[Easton, Douglas F.] Univ Cambridge, Canc Res UK Genet Epidemiol Unit, Cambridge, England.
[Barkardottir, Rosa B.] Landspitali Univ Hosp Iceland, Dept Pathol, Reykjavik, Iceland.
[Barkardottir, Rosa B.] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Ioannidis, John P. A.] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece.
[Ioannidis, John P. A.] Fdn Res & Technol Hellas, Biomed Res Inst, Ioannina, Greece.
[Ioannidis, John P. A.] Tufts Univ, Sch Med, Ctr Genet Epidemiol & Modelling, Boston, MA 02111 USA.
RP Elliott, KS (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
EM jioannid@cc.uoi.gr
RI Macgregor, Stuart/C-6442-2009; Carvajal-Carmona, Luis/B-3882-2010;
Albanes, Demetrius/B-9749-2015; Krogh, Vittorio/K-2628-2016;
Amundadottir, Laufey/L-7656-2016; Tobias, Geoffrey/M-4135-2016;
Ioannidis, John/G-9836-2011; Gallinger, Steven/E-4575-2013; Mann,
Graham/G-4758-2014; hayward, nicholas/C-1367-2015
OI Murabito, Joanne/0000-0002-0192-7516; Zeggini,
Eleftheria/0000-0003-4238-659X; Duell, Eric J/0000-0001-5256-0163;
Eeles, Rosalind/0000-0002-3698-6241; Gudbjartsson,
Daniel/0000-0002-5222-9857; Neal, David/0000-0002-6033-5086; Macgregor,
Stuart/0000-0001-6731-8142; Carvajal-Carmona, Luis/0000-0001-7129-2918;
Krogh, Vittorio/0000-0003-0122-8624; Amundadottir,
Laufey/0000-0003-1859-8971; Tobias, Geoffrey/0000-0002-2878-8253; Mann,
Graham/0000-0003-1301-405X; hayward, nicholas/0000-0003-4760-1033
FU National Institutes of Health [UL1 RR025752, R01-CA88363, RO1-CA83115];
Wellcome Trust [WT075491/Z/04, WT088885/Z/09/Z]; Australian National
Health and Medical Research Council (NHMRC); Swedish Cancer Society
(Cancerfonden),; Swedish Research Council; Predication and prevention of
breast cancer and prostate cancer; Cancer Research [C5047/A8385,
C5047/A7357]; Institute of Cancer Research; Everyman Campaign; Prostate
Cancer Research Foundation; NIHR; Royal Marsden NHS Foundation Trust;
National Cancer Research Institute (NCRI); Medical Research Council;
Cancer Research UK; UK National Institute for Health Research Health
Technology Assessment Programme [96/20/06, 96/20/99]; EU [018827];
NHMRC; Cancer Councils of Queensland; NSW; Victoria; National Heart Lung
and Blood Institute of the National Institutes of Health; National
Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195,
N02-HL-6-4278]; Robert Dawson Evans Endowment
FX JPAI is supported by funding for the Tufts Clinical and Translational
Science Institute and the Center for Genetic Epidemiology and Modeling
is supported by grant UL1 RR025752 from the National Institutes of
Health. KSE is supported by the Wellcome Trust (WT075491/Z/04). EZ is
supported by the Wellcome Trust (WT088885/Z/09/Z). NH and SM were funded
by the Australian National Health and Medical Research Council (NHMRC)
and the National Institutes of Health (grant R01-CA88363). HG is
supported by Swedish Cancer Society (Cancerfonden), Swedish Research
Council, and Linneus grant "Predication and prevention of breast cancer
and prostate cancer''. RE and KM are supported by Cancer Research UK
Grant C5047/A8385; C5047/A7357, The Institute of Cancer Research and The
Everyman Campaign and The Prostate Cancer Research Foundation. The
authors acknowledge support from the NIHR to the Biomedical Research
Centre at The Institute of Cancer Research and The Royal Marsden NHS
Foundation Trust. DEN, JLD and FCH would like to acknowledge the support
of the National Cancer Research Institute (NCRI) formed by the
Department of Health, the Medical Research Council and Cancer Research
UK. The Prostate Testing for Cancer and Treatment (ProtecT) study is
funded by the UK National Institute for Health Research Health
Technology Assessment Programme (projects 96/20/06, 96/20/99). The NCRI
provided funding through ProMPT (Prostate Mechanisms of Progression and
Treatment) and this support is gratefully acknowledged. The Cambridge
prostate biorepository also received funding from the NIHR Comprehensive
Biomedical Research Centre Grant. This support is gratefully
acknowledged. The views and opinions expressed therein are those of the
authors and are not necessarily those of the funding bodies. deCODE
acknowledges grant support from the 6th Framework Program of the EU:
contract 018827 (Polygene). The Australian Melanoma Family Study (AMFS)
was supported by grants from the NHMRC, Cancer Councils of Queensland,
NSW and Victoria, and by National Institutes of Health grant RO1-CA83115
to the GenoMEL consortium. The Framingham Heart Study (FHS) The
Framingham Heart Study of the National Heart Lung and Blood Institute of
the National Institutes of Health and Boston University School of
Medicine were supported by the National Heart, Lung and Blood
Institute's Framingham Heart Study Contract No. N01-HC-25195 and its
contract with Affymetrix, Inc for genotyping services (Contract No.
N02-HL-6-4278). Analyses reflect intellectual input and resource
development from the Framingham Heart Study investigators participating
in the SNP Health Association Resource (SHARe) project. A portion of
this research was conducted using 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.
NR 47
TC 20
Z9 20
U1 0
U2 10
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 MAY 28
PY 2010
VL 5
IS 5
AR e10858
DI 10.1371/journal.pone.0010858
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 603QC
UT WOS:000278222100002
PM 20526366
ER
PT J
AU Rejmanek, D
Miller, MA
Grigg, ME
Crosbie, PR
Conrad, PA
AF Rejmanek, Daniel
Miller, Melissa A.
Grigg, Michael E.
Crosbie, Paul R.
Conrad, Patricia A.
TI Molecular characterization of Sarcocystis neurona strains from opossums
(Didelphis virginiana) and intermediate hosts from Central California
SO VETERINARY PARASITOLOGY
LA English
DT Article
DE Sarcocystis neurona; Opossum (Didelphis virginiana); Sea otter (Enhydra
lutris); Surface antigen genes (SAGs); Microsatellite; Genetic marker
ID EQUINE PROTOZOAL MYELOENCEPHALITIS; POLYMERASE-CHAIN-REACTION; OTTERS
ENHYDRA-LUTRIS; CATS FELIS-DOMESTICUS; DUBEY ET-AL.; TOXOPLASMA-GONDII;
SURFACE-ANTIGEN; SEQUENCE-ANALYSIS; RISK-FACTORS; APICOMPLEXA
AB Sarcocystis neurona is a significant cause of neurological disease in horses and other animals, including the threatened Southern sea otter (Enhydra lutris nereis). Opossums (Didelphis virginiana), the only known definitive hosts for S. neurona in North America, are an introduced species in California. S. neurona DNA isolated from sporocysts and/or infected tissues of 10 opossums, 6 horses, 1 cat, 23 Southern sea otters, and 1 harbor porpoise (Phocoena phocoena) with natural infections was analyzed based on 15 genetic markers, including the first internal transcribed spacer (ITS-1) region; the 25/396 marker; S. neurona surface antigen genes (snSAGs) 2, 3, and 4; and 10 different microsatellites. Based on phylogenetic analysis, most of the S. neurona strains segregated into three genetically distinct groups. Additionally, fifteen S. neurona samples from opossums and several intermediate hosts, including sea otters and horses, were found to be genetically identical across all 15 genetic markers, indicating that fatal encephalitis in Southern sea otters and equine protozoal myeloencephalitis (EPM) in horses is strongly linked to S. neurona sporocysts shed by opossums. (C) 2010 Published by Elsevier B.V.
C1 [Rejmanek, Daniel; Conrad, Patricia A.] Univ Calif Davis, Dept Pathol Microbiol & Immunol, Sch Vet Med, Davis, CA 95616 USA.
[Miller, Melissa A.] Marine Wildlife Vet Care & Res Ctr, Calif Dept Fish & Game, Santa Cruz, CA 95060 USA.
[Grigg, Michael E.] NIAID, Mol Parasitol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Crosbie, Paul R.] Calif State Univ Fresno, Dept Biol, Fresno, CA 93740 USA.
RP Rejmanek, D (reprint author), Univ Calif Davis, Dept Pathol Microbiol & Immunol, Sch Vet Med, 1 Shields Ave, Davis, CA 95616 USA.
EM drejmanek@ucdavis.edu; paconrad@ucdavis.edu
FU Moss Foundation; Morris Animal Foundation; UC Davis Center for Equine
Health; UC Davis Wildlife Health Center; Prescott Fund; NIH; NIAID
(MEG); Canadian Institute for Advanced Research (CIFAR)
FX This research was supported in part through funding from the Moss
Foundation, Morris Animal Foundation, UC Davis Center for Equine Health,
the UC Davis Wildlife Health Center, the Prescott Fund and by the
Intramural Research Program of the NIH and NIAID (MEG). MEG is a scholar
of the Canadian Institute for Advanced Research (CIFAR) Program for
Integrated Microbial Biodiversity. We would like to thank the staff of
the California Department of Fish and Game Marine Wildlife Veterinary
Care and Research Center for their assistance in obtaining sea otter and
opossum samples, Antoinette Marsh for providing several S. neurona
isolates, Frances Gulland, David Casper, and Elizabeth Wheeler for
providing harbor porpoise tissues, Kevin Keel and the Brookfield Zoo for
providing multiple opossum intestinal samples, Amandeep Nandra and Jered
Wendte for sharing unpublished data and primer designs, and Jonna Mazet
for intellectual feedback on the manuscript.
NR 58
TC 10
Z9 11
U1 0
U2 11
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-4017
J9 VET PARASITOL
JI Vet. Parasitol.
PD MAY 28
PY 2010
VL 170
IS 1-2
BP 20
EP 29
DI 10.1016/j.vetpar.2009.12.045
PG 10
WC Parasitology; Veterinary Sciences
SC Parasitology; Veterinary Sciences
GA 609SX
UT WOS:000278678500004
PM 20226596
ER
PT J
AU Fiamma, A
Lissouba, P
Amy, OE
Singh, B
Laeyendecker, O
Quinn, TC
Taljaard, D
Auvert, B
AF Fiamma, Agnes
Lissouba, Pascale
Amy, Oliver E.
Singh, Beverley
Laeyendecker, Oliver
Quinn, Thomas C.
Taljaard, Dirk
Auvert, Bertran
TI Can HIV incidence testing be used for evaluating HIV intervention
programs? A reanalysis of the Orange Farm male circumcision trial
(ANRS-1265)
SO BMC INFECTIOUS DISEASES
LA English
DT Article
ID CAPTURE ENZYME-IMMUNOASSAY; INFECTION; AFRICA; SURVEILLANCE; SPECIMENS;
ASSAY
AB Background: The objective of this study was to estimate the effect of male circumcision (MC) on HIV acquisition estimated using HIV incidence assays and to compare it to the effect measured by survival analysis.
Methods: We used samples collected during the MC randomized controlled trial (ANRS-1265) conducted in Orange Farm (South Africa) among men aged 18 to 24. Among the 2946 samples collected at the last follow-up visit, 194 HIV-positive samples were tested using two incidence assays: Calypte HIV-EIA (BED) and an avidity assay based on the BioRad HIV1/2+O EIA (AI). The results of the assays were also combined (BED-AI). The samples included the 124 participants (4.2% of total) who were HIV-positive at randomization. The protective effect was calculated as one minus the intention-to-treat incidence rate ratio in an uncorrected manner and with correction for misclassifications, with simple theoretical formulae. Theoretical calculations showed that the uncorrected intention-to-treat effect was approximately independent of the value of the incidence assay window period and was the ratio of the number tested recent seroconverters divided by the number tested HIV-negative between the randomization groups. We used cut-off values ranging from 0.325 to 2.27 for BED, 31.6 to 96 for AI and 0.325-31.6 to 1.89-96 for BED-AI. Effects were corrected for long-term specificity using a previously published formula. 95% Confidence intervals (CI) were estimated by bootstrap resampling.
Results: With the highest cut-off values, the uncorrected protective effects evaluated by BED, AI and BED-AI were 50% (95% CI: 27% to 66%), 50% (21% to 69%) and 63% (36% to 81%). The corrections for misclassifications were lower than 50% of the number of tested recent. The corrected effects were 53% (30% to 70%), 55% (25% to 77%) and 67% (38% to 86%), slightly higher than the corresponding uncorrected values. These values were consistent with the previously reported protective effect of 60% (34% to 76%) obtained with survival analysis.
Conclusions: HIV incidence assays may be employed to assess the effect of interventions using cross-sectional data.
C1 [Lissouba, Pascale; Auvert, Bertran] INSERM, U1018, F-94804 Villejuif, France.
[Fiamma, Agnes] Univ California Los Angeles Program Global Hlth, Dept Med, Johannesburg, South Africa.
[Amy, Oliver E.; Laeyendecker, Oliver; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA.
[Amy, Oliver E.; Laeyendecker, Oliver; Quinn, Thomas C.] NIAID, NIH, Bethesda, MD 20892 USA.
[Singh, Beverley] Natl Inst Communicable Dis, ZA-2131 Johannesburg, South Africa.
[Taljaard, Dirk] Progressus Res & Dev, ZA-2115 Johannesburg, South Africa.
[Auvert, Bertran] Hop Ambroise Pare, Assistance Publ Hop Paris, F-92100 Boulogne, France.
[Auvert, Bertran] Univ Versailles, F-78280 Guyancourt, France.
RP Auvert, B (reprint author), INSERM, U1018, F-94804 Villejuif, France.
EM bertran.auvert@uvsq.fr
RI Laeyendecker, Oliver/B-9331-2009;
OI Laeyendecker, Oliver/0000-0002-6429-4760
FU Intramural NIH HHS [Z99 AI999999]; NIAID NIH HHS [U01 AI068613,
U01-AI-068613]; NIMH NIH HHS [U01MH066687, U01MH066688, U01MH066701,
U01MH066702]
NR 24
TC 15
Z9 15
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2334
J9 BMC INFECT DIS
JI BMC Infect. Dis.
PD MAY 27
PY 2010
VL 10
AR 137
DI 10.1186/1471-2334-10-137
PG 10
WC Infectious Diseases
SC Infectious Diseases
GA 625LD
UT WOS:000279895800002
PM 20507545
ER
PT J
AU Hou, SJ
Kovac, P
AF Hou, Shu-jie
Kovac, Pavol
TI Enhanced stereoselectivity of alpha-mannosylation under thermodynamic
control using trichloroacetimidates
SO CARBOHYDRATE RESEARCH
LA English
DT Article
DE O-Specific polysaccharide; Cholera; Vibrio cholerae O1; Oligosaccharide
synthesis; Glycosylation; beta-Mannosylation
ID VIBRIO-CHOLERAE O-1; O-POLYSACCHARIDE; SEROTYPE INABA; HEXASACCHARIDE
FRAGMENTS; ANTIGENIC DETERMINANTS; C-13-NMR SPECTRA; BLOCK SYNTHESIS;
SIDE-CHAIN; OGAWA; DISACCHARIDE
AB O-Specific polysaccharides of Vibrio cholerae 01, serotypes Inaba and Ogawa, consist of alpha-(1-2)-linked N-(3-deoxy-L-glycero-tetronyl)perosamine (4-amino-4,6-dideoxy-D-mannose) The blockwise synthesis of larger fragments of such O-PSs involves oligosaccharide glycosyl donors that contain a nonparticipating 2-O-glycosyl group at the position vicinal to the anomeric center where the new glycosidic linkage is formed Such glycosyl donors may bear at C-4 either a latent acylamino (e g, azido) or the 3-deoxy-L-glycero-tetronamido group. While monosaccharide glycosyl donors, even those bearing a nonparticipating group at O-2 (e g, methyl), and the 4-N-(3-deoxy-L-glycero-tetronyl) side chain form alpha-linked oligosaccharides with excellent stereoselectivity, alpha-mannosylation with analogous oligosaccharide donors in this series is adversely affected by the presence of the side chain Consequently, the unwanted beta-product is formed in a considerable amount Conducting the reaction at elevated temperature under thermodynamic control substantially enhances formation of the alpha-linked oligosaccharide This effect is much more pronounced when glycosyl trichloroacetimidates, rather than thioglycosides or glycosyl chlorides, are used as glycosyl donors Published by Elsevier Ltd
C1 [Hou, Shu-jie; Kovac, Pavol] NIDDK, LBC, NIH, Bethesda, MD 20892 USA.
RP Kovac, P (reprint author), NIDDK, LBC, NIH, Bethesda, MD 20892 USA.
RI Kovac, Pavol/B-8813-2008
OI Kovac, Pavol/0000-0001-5044-3449
FU NIH, NIDDK
FX This research was supported by the Intramural Research Program of the
NIH, NIDDK.
NR 27
TC 5
Z9 5
U1 0
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0008-6215
J9 CARBOHYD RES
JI Carbohydr. Res.
PD MAY 27
PY 2010
VL 345
IS 8
BP 999
EP 1007
DI 10.1016/j.carres.2010.03.025
PG 9
WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 610PY
UT WOS:000278747700003
PM 20381793
ER
PT J
AU Ghorai, S
Chowdhury, S
Pal, S
Banik, SP
Mukherjee, S
Khowala, S
AF Ghorai, Shakuntala
Chowdhury, Sudeshna
Pal, Swagata
Banik, Samudra Prosad
Mukherjee, Sumana
Khowala, Suman
TI Enhanced activity and stability of cellobiase (beta-glucosidase: EC
3.2.1.21) produced in the presence of 2-deoxy-D-glucose from the fungus
Termitomyces clypeatus
SO CARBOHYDRATE RESEARCH
LA English
DT Article
DE beta-Glucosidase; Cellulolytic enzymes; 2-Deoxy-D-glucose; Glycosylation
inhibitor; Catalytic efficiency; Termitomyces clypeatus
ID TRICHODERMA-REESEI; ASPERGILLUS-NIGER; PARTIAL DEGLYCOSYLATION;
SENSITIVE METHOD; PICHIA-PASTORIS; GLYCOSYLATION; RECOMBINANT; SUCRASE;
CONFORMATION; AGGREGATION
AB Generally less glycosylation or deglycosylation has a detrimental effect on enzyme activity and stability Increased production and secretion of cellobiase was earlier obtained in the presence of the glycosylation inhibitor 2-deoxy-D-glucose in filamentous fungus Termitomyces clypeatus [Mukherjee, S: Chowdhury, S., Ghorai, S Pal. S Khowala, S Biotechnol Lett. 2006, 28, 1773-1778] In this study the enzyme was purified from the culture medium by ultrafiltration and gel-permeation, ion-exchange and high-performance liquid chromatography, and its catalytic activity was six times higher compared to the control enzyme K-m and V-max of the purified enzyme were measured as 0 187 mM and 0.018 U mg(-1), respectively, using pNPG as the substrate. The enzyme had temperature and pH optima at 45 degrees C and pH 5.4, respectively, and retained full activity in a pH range of 5-8 and temperatures of 30-60 degrees C. Interestingly less glycosylated cellobiase was resistant towards proteolytic as well as endoglycosidase-H digestion and showed higher stability than native enzyme due to increased aggregation of the protein The enzyme also showed higher specific activity in the presence of cellobiose and pNPG and less susceptibility towards salts and different chemical agents The beta-glucosidase can be considered as a potentially useful enzyme in various food-processing, pharmaceutical and fermentation industries. (C) 2010 Elsevier Ltd All rights reserved
C1 [Ghorai, Shakuntala; Chowdhury, Sudeshna; Pal, Swagata; Banik, Samudra Prosad; Khowala, Suman] Govt India, Indian Inst Chem Biol, Unit CSIR, Drug Dev & Biotechnol Div, Kolkata 700032, India.
[Mukherjee, Sumana] NCI, Pathol Lab, Adv Technol Ctr, Bethesda, MD 20892 USA.
[Mukherjee, Sumana] NCI, Urol Oncol Branch, Ctr Canc Res, Adv Technol Ctr, Bethesda, MD 20892 USA.
RP Khowala, S (reprint author), Govt India, Indian Inst Chem Biol, Unit CSIR, Drug Dev & Biotechnol Div, 4,Raja S C Mullick Rd, Kolkata 700032, India.
FU DBT; CSIR, Govt. of India
FX Financial support to S.G. by DBT and CSIR, Govt. of India is duly
acknowledged Sincere thanks are due to Dr. Debashis Mukherjee (Saha
Institute of Nuclear Physics, Kolkata) for attempting MALDI-TOF analysis
of the enzyme and Dr. Paramjit Kaur, Institute of Microbial Technology,
Sector 39-A. Chandigarh for N-terminal sequencing
NR 44
TC 14
Z9 14
U1 1
U2 15
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0008-6215
EI 1873-426X
J9 CARBOHYD RES
JI Carbohydr. Res.
PD MAY 27
PY 2010
VL 345
IS 8
BP 1015
EP 1022
DI 10.1016/j.carres.2010.02.021
PG 8
WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 610PY
UT WOS:000278747700005
PM 20382376
ER
PT J
AU Romagnoli, R
Baraldi, PG
Cruz-Lopez, O
Cara, CL
Carrion, MD
Brancale, A
Hamel, E
Chen, LC
Bortolozzi, R
Basso, G
Viola, G
AF Romagnoli, Romeo
Baraldi, Pier Giovanni
Cruz-Lopez, Olga
Cara, Carlota Lopez
Carrion, Maria Dora
Brancale, Andrea
Hamel, Ernest
Chen, Longchuan
Bortolozzi, Roberta
Basso, Giuseppe
Viola, Giampietro
TI Synthesis and Antitumor Activity of 1,5-Disubstituted 1,2,4-Triazoles as
Cis-Restricted Combretastatin Analogues
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID A-4 ANALOGS; CELL-DEATH; IN-VITRO; TUBULIN POLYMERIZATION; MICROTUBULE
DYNAMICS; MEDICINAL CHEMISTRY; COLCHICINE SITE; A4 PHOSPHATE;
CYTOCHROME-C; CANCER CELLS
AB A series of 1-aryl-5-(3',4',5'-trimethoxyphenyl) derivatives and their related 1-(3',4',5'-trimethoxyphenyl)5-aryl-1,2,4-triazoles, designed as cis-restricted combretastatin analogues, were synthesized and evaluated for antiproliferative activity, inhibitory effects on tubulin polymerization, cell cycle effects, and apoptosis induction. Their activity was greater than, or comparable with, that of the reference compound CA-4. Flow cytometry studies showed that HeLa and Jurkat cells treated with the most active compounds 4l and 4o were arrested in the G2/M phase of the cell cycle in a concentration dependent manner. This effect was accompanied by apoptosis of the cells, mitochondrial depolarization, generation of reactive oxygen species, activation of caspase-3, and PA RP cleavage. Compound 41 was also shown to have potential antivascular activity, since it induced endothelial cell shape change in vitro and disrupted the sprouting of endothelial cells in the chick aortic ring assay.
C1 [Romagnoli, Romeo; Baraldi, Pier Giovanni; Cruz-Lopez, Olga; Cara, Carlota Lopez; Carrion, Maria Dora] Univ Ferrara, Dipartimento Sci Farmaceut, I-44100 Ferrara, Italy.
[Brancale, Andrea] Cardiff Univ, Welsh Sch Pharm, Cardiff CF10 3NB, S Glam, Wales.
[Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA.
[Chen, Longchuan] VA Med Ctr, Dept Pathol, Long Beach, CA 90822 USA.
[Bortolozzi, Roberta; Basso, Giuseppe; Viola, Giampietro] Univ Padua, Dipartimento Pediat, Lab Oncoematol, I-35131 Padua, Italy.
RP Romagnoli, R (reprint author), Univ Ferrara, Dipartimento Sci Farmaceut, I-44100 Ferrara, Italy.
EM rmr@unife.it; giampietro.viola1@unipd.it
RI Viola, Giampietro/I-4095-2012; Brancale, Andrea/N-9445-2014; Bortolozzi,
Roberta/D-4950-2015; LOPEZ-CARA, LUISA CARLOTA/F-9686-2014; Carrion, M.
Dora/G-8638-2015; Romagnoli, Romeo/G-9887-2015; Baraldi, Pier
Giovanni/B-7933-2017; Cruz-Lopez, Olga /F-3060-2017
OI Viola, Giampietro/0000-0001-9329-165X; Brancale,
Andrea/0000-0002-9728-3419; BASSO, GIUSEPPE/0000-0002-2634-9302;
Bortolozzi, Roberta/0000-0002-3357-4815; LOPEZ-CARA, LUISA
CARLOTA/0000-0003-1142-6448; Carrion, M. Dora/0000-0002-6794-3949;
FU Intramural NIH HHS [Z99 CA999999]
NR 59
TC 82
Z9 84
U1 2
U2 19
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 MAY 27
PY 2010
VL 53
IS 10
BP 4248
EP 4258
DI 10.1021/jm100245q
PG 11
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 597OF
UT WOS:000277766900035
PM 20420439
ER
PT J
AU Leitner, WW
Bergmann-Leitner, ES
Angov, E
AF Leitner, Wolfgang W.
Bergmann-Leitner, Elke S.
Angov, Evelina
TI Comparison of Plasmodium berghei challenge models for the evaluation of
pre-erythrocytic malaria vaccines and their effect on perceived vaccine
efficacy
SO MALARIA JOURNAL
LA English
DT Article
ID CIRCUMSPOROZOITE-PROTEIN; IMMUNE-RESPONSES; T-CELLS; IRRADIATED
SPOROZOITES; EXPERIMENTAL HOSTS; MURINE MALARIA; MOSQUITO BITE;
LIVER-STAGES; PROTECTION; INFECTION
AB Background: The immunological mechanisms responsible for protection against malaria infection vary among Plasmodium species, host species and the developmental stage of parasite, and are poorly understood. A challenge with live parasites is the most relevant approach to testing the efficacy of experimental malaria vaccines. Nevertheless, in the mouse models of Plasmodium berghei and Plasmodium yoelii, parasites are usually delivered by intravenous injection. This route is highly artificial and particularly in the P. berghei model produces inconsistent challenge results. The initial objective of this study was to compare an optimized intravenous (IV) delivery challenge model with an optimized single infectious mosquito bite challenge model. Finding shortcomings of both approaches, an alternative approach was explored, i. e., the subcutaneous challenge.
Methods: Mice were infected with P. berghei sporozoites by intravenous (tail vein) injection, single mosquito bite, or subcutaneous injection of isolated parasites into the subcutaneous pouch at the base of the hind leg. Infection was determined in blood smears 7 and 14 days later. To determine the usefulness of challenge models for vaccine testing, mice were immunized with circumsporozoite-based DNA vaccines by gene gun.
Results: Despite modifications that allowed infection with a much smaller than reported number of parasites, the IV challenge remained insufficiently reliable and reproducible. Variations in the virulence of the inoculum, if not properly monitored by the rigorous inclusion of sporozoite titration curves in each experiment, can lead to unacceptable variations in reported vaccine efficacies. In contrast, mice with different genetic backgrounds were consistently infected by a single mosquito bite, without overwhelming vaccine-induced protective immune responses. Because of the logistical challenges associated with the mosquito bite model, the subcutaneous challenge route was optimized. This approach, too, yields reliable challenge results, albeit requiring a relatively large inoculum.
Conclusions: Although a single bite by P. berghei infected Anopheles mosquitoes was superior to the IV challenge route, it is laborious. However, any conclusive evaluation of a pre-erythrocytic malaria vaccine candidate should require challenge through the natural anatomic target site of the parasite, the skin. The subcutaneous injection of isolated parasites represents an attractive compromise. Similar to the mosquito bite model, it allows vaccine-induced antibodies to exert their effect and is, therefore not as prone to the artifacts of the IV challenge.
C1 [Leitner, Wolfgang W.; Bergmann-Leitner, Elke S.; Angov, Evelina] Walter Reed Army Inst Res, Silver Spring, MD 20910 USA.
[Leitner, Wolfgang W.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Leitner, WW (reprint author), Walter Reed Army Inst Res, Silver Spring, MD 20910 USA.
EM wolfgang_leitner@nih.gov
RI Bergmann-Leitner, Elke/B-3548-2011; Leitner, Wolfgang/F-5741-2011
OI Bergmann-Leitner, Elke/0000-0002-8571-8956; Leitner,
Wolfgang/0000-0003-3125-5922
FU United States Army Medical Research and Materiel Command
FX The authors would like to thank Dr. Jeffrey Lyon, for guidance on study
design, Matthew C. Seguin Howard D. Stacey and Elizabeth Duncan for
their expertise and technical assistance; Dr. Imogene Schneider, Megan
Dowler, Jacqulin Glass and Dr. Tatyana Savranskaya for providing
infected mosquitoes and for advice and technical assistance; and Diane
Cooper (NIH Library) for editing. This work was supported by the United
States Army Medical Research and Materiel Command.
NR 46
TC 15
Z9 15
U1 0
U2 3
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 MAY 27
PY 2010
VL 9
AR 145
DI 10.1186/1475-2875-9-145
PG 12
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 629BA
UT WOS:000280167800001
PM 20507620
ER
PT J
AU Chappie, JS
Acharya, S
Leonard, M
Schmid, SL
Dyda, F
AF Chappie, Joshua S.
Acharya, Sharmistha
Leonard, Marilyn
Schmid, Sandra L.
Dyda, Fred
TI G domain dimerization controls dynamin's assembly-stimulated GTPase
activity
SO NATURE
LA English
DT Article
ID CLATHRIN-MEDIATED ENDOCYTOSIS; DEPENDENT CONFORMATIONAL-CHANGES;
IN-VIVO; ISOMORPHOUS REPLACEMENT; CRYSTAL-STRUCTURE; VESICLE FORMATION;
CONSTRICTION; MECHANISM; MEMBRANE; PROTEINS
AB Dynamin is an atypical GTPase that catalyses membrane fission during clathrin-mediated endocytosis. The mechanisms of dynamin's basal and assembly-stimulated GTP hydrolysis are unknown, though both are indirectly influenced by the GTPase effector domain (GED). Here we present the 2.0 angstrom resolution crystal structure of a human dynamin 1-derived minimal GTPase-GED fusion protein, which was dimeric in the presence of the transition state mimic GDP.AlF(4)(-). The structure reveals dynamin's catalytic machinery and explains how assembly-stimulated GTP hydrolysis is achieved through G domain dimerization. A sodium ion present in the active site suggests that dynamin uses a cation to compensate for the developing negative charge in the transition state in the absence of an arginine finger. Structural comparison to the rat dynamin G domain reveals key conformational changes that promote G domain dimerization and stimulated hydrolysis. The structure of the GTPase-GED fusion protein dimer provides insight into the mechanisms underlying dynamin-catalysed membrane fission.
C1 [Chappie, Joshua S.; Acharya, Sharmistha; Leonard, Marilyn; Schmid, Sandra L.] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA.
[Chappie, Joshua S.; Dyda, Fred] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Schmid, SL (reprint author), Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA.
EM slschmid@scripps.edu; dyda@helix.nih.gov
FU NIH [GM42455, MH61345]; National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK) of the NIH; NIMH [MH081419]; US Department of
Energy, Basic Energy Sciences, Office of Science [W-31-109-Eng-38]
FX We thank V. Lukiyanchuk for assistance in cloning and purification; A.
Hickman, J. Mindell and R. Ramachandran for discussions and technical
advice; T. Pucadyil and R. Ramachandran for critical reading of the
manuscript; J. Hinshaw and J. Mears for providing the unpublished
coordinates for the GTPase docking model derived from their cryo-EM
docking studies; and R. Stevens and I. Wilson for structural advice,
guidance and the use of their laboratory facilities in the early stages
of this work. This work was supported by NIH grants GM42455 and MH61345
(to S. L. S.) and the Intramural Program of the National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK) of the NIH. J. S. C.
was supported by a Ruth Kirschstein individual predoctoral fellowship
from the NIMH (MH081419) and by a postdoctoral Intramural Research
Training Award from NIDDK. Data were collected at the SER-CAT 22-ID
beamline at the Advanced Photon Source, Argonne National Laboratory. Use
of the APS was supported by the US Department of Energy, Basic Energy
Sciences, Office of Science, under contract no. W-31-109-Eng-38.
NR 55
TC 116
Z9 117
U1 0
U2 17
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD MAY 27
PY 2010
VL 465
IS 7297
BP 435
EP U54
DI 10.1038/nature09032
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 601FM
UT WOS:000278043700025
PM 20428113
ER
PT J
AU Carney, RSE
Mangin, JM
Hayes, L
Mansfield, K
Sousa, VH
Fishell, G
Machold, RP
Ahn, S
Gallo, V
Corbin, JG
AF Carney, Rosalind S. E.
Mangin, Jean-Marie
Hayes, Lindsay
Mansfield, Kevin
Sousa, Vitor H.
Fishell, Gord
Machold, Robert P.
Ahn, Sohyun
Gallo, Vittorio
Corbin, Joshua G.
TI Sonic hedgehog expressing and responding cells generate neuronal
diversity in the medial amygdala
SO NEURAL DEVELOPMENT
LA English
DT Article
ID MOLECULAR SPECIFICATION; FUNCTIONAL IMPLICATIONS; VENTRAL TELENCEPHALON;
INTERNEURON SUBTYPES; GANGLIONIC EMINENCE; MOUSE TELENCEPHALON;
SUBPALLIAL BOUNDARY; PROGENITOR POOLS; GLOBUS-PALLIDUS; NERVOUS-SYSTEM
AB Background: The mammalian amygdala is composed of two primary functional subdivisions, classified according to whether the major output projection of each nucleus is excitatory or inhibitory. The posterior dorsal and ventral subdivisions of the medial amygdala, which primarily contain inhibitory output neurons, modulate specific aspects of innate socio-sexual and aggressive behaviors. However, the development of the neuronal diversity of this complex and important structure remains to be fully elucidated.
Results: Using a combination of genetic fate-mapping and loss-of-function analyses, we examined the contribution and function of Sonic hedgehog (Shh)-expressing and Shh-responsive (Nkx2-1(+) and Gli1(+)) neurons in the medial amygdala. Specifically, we found that Shh- and Nkx2-1-lineage cells contribute differentially to the dorsal and ventral subdivisions of the postnatal medial amygdala. These Shh- and Nkx2-1-lineage neurons express overlapping and non-overlapping inhibitory neuronal markers, such as Calbindin, FoxP2, nNOS and Somatostatin, revealing diverse fate contributions in discrete medial amygdala nuclear subdivisions. Electrophysiological analysis of the Shh-derived neurons additionally reveals an important functional diversity within this lineage in the medial amygdala. Moreover, inducible Gli1(CreER(T2)) temporal fate mapping shows that early-generated progenitors that respond to Shh signaling also contribute to medial amygdala neuronal diversity. Lastly, analysis of Nkx2-1 mutant mice demonstrates a genetic requirement for Nkx2-1 in inhibitory neuronal specification in the medial amygdala distinct from the requirement for Nkx2-1 in cerebral cortical development.
Conclusions: Taken together, these data reveal a differential contribution of Shh-expressing and Shh-responding cells to medial amygdala neuronal diversity as well as the function of Nkx2-1 in the development of this important limbic system structure.
C1 [Hayes, Lindsay; Ahn, Sohyun] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, Unit Dev Neurogenet, Bethesda, MD 20892 USA.
[Sousa, Vitor H.; Fishell, Gord; Machold, Robert P.] NYU, Neurosci Program, Smilow Res Ctr, Sch Med, New York, NY 10016 USA.
[Sousa, Vitor H.; Fishell, Gord; Machold, Robert P.] NYU, Dept Cell Biol, Smilow Res Ctr, Sch Med, New York, NY 10016 USA.
[Carney, Rosalind S. E.; Mangin, Jean-Marie; Mansfield, Kevin; Gallo, Vittorio; Corbin, Joshua G.] Childrens Natl Med Ctr, Ctr Res Neurosci, Childrens Res Inst, Washington, DC 20010 USA.
RP Corbin, JG (reprint author), Salk Inst Biol Studies, Mol Neurobiol Lab MNL O, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM jcorbin@cnmcresearch.org
RI Sousa, Vitor/E-3679-2016
OI Sousa, Vitor/0000-0001-8768-2742
NR 70
TC 29
Z9 32
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1749-8104
J9 NEURAL DEV
JI Neural Dev.
PD MAY 27
PY 2010
VL 5
AR 14
DI 10.1186/1749-8104-5-14
PG 17
WC Developmental Biology; Neurosciences
SC Developmental Biology; Neurosciences & Neurology
GA 617MJ
UT WOS:000279284600001
PM 20507551
ER
PT J
AU Minamimoto, T
Saunders, RC
Richmond, BJ
AF Minamimoto, Takafumi
Saunders, Richard C.
Richmond, Barry J.
TI Monkeys Quickly Learn and Generalize Visual Categories without Lateral
Prefrontal Cortex
SO NEURON
LA English
DT Article
ID TEMPORAL CORTEX; WORKING-MEMORY; FRONTAL-CORTEX; RHESUS-MONKEYS; RHINAL
CORTEX; REWARD; REPRESENTATION; IMPAIRMENTS; BEHAVIOR; LESIONS
AB Categorization is a basic mental process that helps individuals distinguish among groups of negative and positive objects, e.g., poisons and nutrients, or predators and prey. Monkey experiments have suggested that lateral prefrontal cortex (LPFC) participates in learning and processing visual categories. However, in humans category specific visual agnosia follows inferior temporal cortex but not LPFC damage. Here, we use a new behavioral approach to show that both normal monkeys and those with bilateral removal of LPFC learn and generalize perceptual categories of related visual stimuli rapidly without explicit instruction. These results strongly indicate that visual categorization occurs at some earlier stage of feed-forward processing, presumably in temporal cortex, without top-down information from LPFC.
C1 [Minamimoto, Takafumi; Saunders, Richard C.; Richmond, Barry J.] NIMH, Neuropsychol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Minamimoto, Takafumi] Natl Inst Radiol Sci, Dept Mol Neuroimaging, Mol Imaging Ctr, Chiba 2638555, Japan.
RP Minamimoto, T (reprint author), NIMH, Neuropsychol Lab, NIH, Dept Hlth & Human Serv, Bldg 9, Bethesda, MD 20892 USA.
EM minamoto@nirs.go.jp; bjr@ln.nimh.nih.gov
RI Minamimoto, Takafumi/D-6610-2012
OI Minamimoto, Takafumi/0000-0003-4305-0174
FU National Institute of Mental Health; JSPS Research Fellowship for
Japanese Biomedical and Behavioral Researchers at NIH; Takeda Science
Foundation
FX We thank D.P. Soucy, C. Yang, P. Chen, Y. Matsuda, and A. Lerchner for
their technical assistance, M. Yamada for advice on literature, and K.
Yamamoto, J.S. Simmons, and Y. Sugase-Miyamoto, and N. Matsumoto for the
comments on the manuscript, and other helpful comments. This study was
supported by the Intramural Research Program of the National Institute
of Mental Health. T.M. was partly supported by JSPS Research Fellowship
for Japanese Biomedical and Behavioral Researchers at NIH, and by Takeda
Science Foundation. The views expressed in this article do not
necessarily represent the views of the NIMH, NIH, or the United States
Government.
NR 29
TC 22
Z9 23
U1 0
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD MAY 27
PY 2010
VL 66
IS 4
BP 501
EP 507
DI 10.1016/j.neuron.2010.04.010
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 610WX
UT WOS:000278771100006
PM 20510855
ER
PT J
AU Carlo, WA
Finer, NN
Walsh, MC
Rich, W
Gantz, MG
Laptook, AR
Yoder, BA
Faix, RG
Das, A
Poole, WK
Schibler, K
Newman, NS
Ambalavanan, N
Frantz, ID
Piazza, AJ
Sanchez, PJ
Morris, BH
Laroia, N
Phelps, DL
Poindexter, BB
Cotten, CM
Van Meurs, KP
Duara, S
Narendran, V
Sood, BG
O'Shea, TM
Bell, EF
Ehrenkranz, RA
Watterberg, KL
Higgins, RD
Jobe, AH
Caplan, MS
Oh, W
Hensman, AM
Gingras, D
Barnett, S
Lillie, S
Francis, K
Andrews, D
Angela, K
Fanaroff, AA
Siner, BS
Zadell, A
DiFiore, J
Donovan, EF
Bridges, K
Alexander, B
Grisby, C
Mersmann, MW
Mincey, HL
Hessling, J
Goldberg, RN
Auten, KJ
Fisher, KA
Foy, KA
Siaw, G
Stoll, BJ
Buchter, S
Carlton, DP
Hale, EC
Hutchinson, AK
Archer, SW
Lemons, JA
Hamer, F
Herron, DE
Miller, LC
Wilson, LD
Berberich, MA
Blaisdell, CJ
Gail, DB
Kiley, JP
Cunningham, M
Hastings, BK
Irene, AR
Auman, JO
Huitema, CP
Pickett, JW
Wallace, D
Zaterka-Baxter, KM
Stevenson, DK
Ball, MB
Proud, MS
Fiascone, JM
Furey, A
MacKinnon, BL
Nylen, E
Collins, MV
Cosby, SS
Phillips, VA
Rasmussen, MR
Wozniak, PR
Arnell, K
Bridge, R
Demetrio, C
Widness, JA
Klein, JM
Johnson, KJ
Everett-Thomas, R
Ohls, RK
Rohr, J
Lacy, CB
Markowitz, GD
Reubens, LJ
Burnell, E
Rosenfeld, CR
Salhab, WA
Guzman, A
Hensley, G
Lepps, MH
Miller, NA
Allen, J
Grau, L
Martin, M
Solis, A
Vasil, DM
Wilder, K
Kennedy, KA
Tyson, JE
Harris, BF
Lis, AE
Martin, S
McDavid, GE
Tate, PL
Wright, SL
Burnett, J
Jensen, JJ
Osborne, KA
Spencer, C
Weaver-Lewis, K
Peters, NJ
Shankaran, S
Bara, R
Billian, E
Johnson, M
Bhandari, V
Jacobs, HC
Cervone, P
Gettner, P
Konstantino, M
Poulsen, J
Taft, J
Avery, G
Gleason, CA
Allen, MC
Bangdiwala, SI
Blaisdell, CJ
Boyle, RJ
Clemons, T
D'Alton, ME
Das, A
Gail, DB
Hunt, C
Keszler, M
Poole, WK
Redmond, CK
Ross, MG
Thomson, MA
Weiner, SJ
Willinger, M
Markowitz, GD
Hutchinson, AK
Wallace, DK
Freedman, SF
AF Carlo, Waldemar A.
Finer, Neil N.
Walsh, Michele C.
Rich, Wade
Gantz, Marie G.
Laptook, Abbot R.
Yoder, Bradley A.
Faix, Roger G.
Das, Abhik
Poole, W. Kenneth
Schibler, Kurt
Newman, Nancy S.
Ambalavanan, Namasivayam
Frantz, Ivan D., III
Piazza, Anthony J.
Sanchez, Pablo J.
Morris, Brenda H.
Laroia, Nirupama
Phelps, Dale L.
Poindexter, Brenda B.
Cotten, C. Michael
Van Meurs, Krisa P.
Duara, Shahnaz
Narendran, Vivek
Sood, Beena G.
O'Shea, T. Michael
Bell, Edward F.
Ehrenkranz, Richard A.
Watterberg, Kristi L.
Higgins, Rosemary D.
Jobe, A. H.
Caplan, M. S.
Oh, W.
Hensman, A. M.
Gingras, D.
Barnett, S.
Lillie, S.
Francis, K.
Andrews, D.
Angela, K.
Fanaroff, A. A.
Siner, B. S.
Zadell, A.
DiFiore, J.
Donovan, E. F.
Bridges, K.
Alexander, B.
Grisby, C.
Mersmann, M. W.
Mincey, H. L.
Hessling, J.
Goldberg, R. N.
Auten, K. J.
Fisher, K. A.
Foy, K. A.
Siaw, G.
Stoll, B. J.
Buchter, S.
Carlton, D. P.
Hale, E. C.
Hutchinson, A. K.
Archer, S. W.
Lemons, J. A.
Hamer, F.
Herron, D. E.
Miller, L. C.
Wilson, L. D.
Berberich, M. A.
Blaisdell, C. J.
Gail, D. B.
Kiley, J. P.
Cunningham, M.
Hastings, B. K.
Irene, A. R.
Auman, J. O'D.
Huitema, C. P.
Pickett, J. W., II
Wallace, D.
Zaterka-Baxter, K. M.
Stevenson, D. K.
Ball, M. B.
Proud, M. S.
Fiascone, J. M.
Furey, A.
MacKinnon, B. L.
Nylen, E.
Collins, M. V.
Cosby, S. S.
Phillips, V. A.
Rasmussen, M. R.
Wozniak, P. R.
Arnell, K.
Bridge, R.
Demetrio, C.
Widness, J. A.
Klein, J. M.
Johnson, K. J.
Everett-Thomas, R.
Ohls, R. K.
Rohr, J.
Lacy, C. B.
Markowitz, G. D.
Reubens, L. J.
Burnell, E.
Rosenfeld, C. R.
Salhab, W. A.
Guzman, A.
Hensley, G.
Lepps, M. H.
Miller, N. A.
Allen, J.
Grau, L.
Martin, M.
Solis, A.
Vasil, D. M.
Wilder, K.
Kennedy, K. A.
Tyson, J. E.
Harris, B. F.
Lis, A. E.
Martin, S.
McDavid, G. E.
Tate, P. L.
Wright, S. L.
Burnett, J.
Jensen, J. J.
Osborne, K. A.
Spencer, C.
Weaver-Lewis, K.
Peters, N. J.
Shankaran, S.
Bara, R.
Billian, E.
Johnson, M.
Bhandari, V.
Jacobs, H. C.
Cervone, P.
Gettner, P.
Konstantino, M.
Poulsen, J.
Taft, J.
Avery, G.
Gleason, C. A.
Allen, M. C.
Bangdiwala, S. I.
Blaisdell, C. J.
Boyle, R. J.
Clemons, T.
D'Alton, M. E.
Das, A.
Gail, D. B.
Hunt, C.
Keszler, M.
Poole, W. K.
Redmond, C. K.
Ross, M. G.
Thomson, M. A.
Weiner, S. J.
Willinger, M.
Markowitz, G. D.
Hutchinson, A. K.
Wallace, D. K.
Freedman, S. F.
CA Eunice Kennedy Shriver NICHD
TI Target Ranges of Oxygen Saturation in Extremely Preterm Infants.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID BRONCHOPULMONARY DYSPLASIA; SEVERE RETINOPATHY; PREMATURITY; TRIAL;
PATHOGENESIS; OUTCOMES; THERAPY; INJURY; BABIES
AB Background: Previous studies have suggested that the incidence of retinopathy is lower in preterm infants with exposure to reduced levels of oxygenation than in those exposed to higher levels of oxygenation. However, it is unclear what range of oxygen saturation is appropriate to minimize retinopathy without increasing adverse outcomes.
Methods: We performed a randomized trial with a 2-by-2 factorial design to compare target ranges of oxygen saturation of 85 to 89% or 91 to 95% among 1316 infants who were born between 24 weeks 0 days and 27 weeks 6 days of gestation. The primary outcome was a composite of severe retinopathy of prematurity (defined as the presence of threshold retinopathy, the need for surgical ophthalmologic intervention, or the use of bevacizumab), death before discharge from the hospital, or both. All infants were also randomly assigned to continuous positive airway pressure or intubation and surfactant.
Results: The rates of severe retinopathy or death did not differ significantly between the lower-oxygen-saturation group and the higher-oxygen-saturation group (28.3% and 32.1%, respectively; relative risk with lower oxygen saturation, 0.90; 95% confidence interval [CI], 0.76 to 1.06; P=0.21). Death before discharge occurred more frequently in the lower-oxygen-saturation group (in 19.9% of infants vs. 16.2%; relative risk, 1.27; 95% CI, 1.01 to 1.60; P=0.04), whereas severe retinopathy among survivors occurred less often in this group (8.6% vs. 17.9%; relative risk, 0.52; 95% CI, 0.37 to 0.73; P<0.001). There were no significant differences in the rates of other adverse events.
Conclusions: A lower target range of oxygenation (85 to 89%), as compared with a higher range (91 to 95%), did not significantly decrease the composite outcome of severe retinopathy or death, but it resulted in an increase in mortality and a substantial decrease in severe retinopathy among survivors. The increase in mortality is a major concern, since a lower target range of oxygen saturation is increasingly being advocated to prevent retinopathy of prematurity. (ClinicalTrials.gov number, NCT00233324.)
N Engl J Med 2010;362:1959-69.
C1 [Carlo, Waldemar A.; Ambalavanan, Namasivayam] Univ Alabama, Div Neonatol, Birmingham, AL 35294 USA.
[Finer, Neil N.; Rich, Wade] Univ Calif San Diego, San Diego, CA 92103 USA.
[Walsh, Michele C.; Newman, Nancy S.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA.
[Gantz, Marie G.; Poole, W. Kenneth] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA.
[Cotten, C. Michael] Duke Univ, Dept Pediat, Durham, NC 27706 USA.
[O'Shea, T. Michael] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA.
[Laptook, Abbot R.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA.
[Yoder, Bradley A.; Faix, Roger G.] Univ Utah, Sch Med, Dept Pediat, Div Neonatol, Salt Lake City, UT USA.
[Das, Abhik] RTI Int, Stat & Epidemiol Unit, Rockville, MD USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Schibler, Kurt; Narendran, Vivek] Univ Cincinnati, Dept Pediat, Cincinnati, OH 45221 USA.
[Frantz, Ivan D., III] Floating Hosp Children, Tufts Med Ctr, Div Newborn Med, Dept Pediat, Boston, MA USA.
[Sanchez, Pablo J.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA.
[Piazza, Anthony J.] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA.
[Piazza, Anthony J.] Childrens Healthcare Atlanta, Atlanta, GA USA.
[Morris, Brenda H.] Univ Texas Med Sch Houston, Dept Pediat, Houston, TX USA.
[Laroia, Nirupama; Phelps, Dale L.] Univ Rochester, Sch Med & Dent, Rochester, NY USA.
[Poindexter, Brenda B.] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN USA.
[Van Meurs, Krisa P.] Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA.
[Duara, Shahnaz] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Sood, Beena G.] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
[Bell, Edward F.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA.
[Ehrenkranz, Richard A.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
[Watterberg, Kristi L.] Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA.
[Caplan, M. S.] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA.
Brown Univ, Alpert Med Sch, Providence, RI 02912 USA.
[Oh, W.; Hensman, A. M.; Gingras, D.; Barnett, S.; Lillie, S.; Francis, K.; Andrews, D.; Angela, K.] Rainbow Babies & Childrens Hosp, Cleveland, OH USA.
[Fanaroff, A. A.; Siner, B. S.; Zadell, A.; DiFiore, J.] Univ Cincinnati Hosp, Cincinnati, OH USA.
[Fanaroff, A. A.; Siner, B. S.; Zadell, A.; DiFiore, J.] Good Samaritan Hosp, Cincinnati, OH USA.
[Fanaroff, A. A.; Siner, B. S.; Zadell, A.; DiFiore, J.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA.
[Donovan, E. F.; Bridges, K.; Alexander, B.; Grisby, C.; Mersmann, M. W.; Mincey, H. L.; Hessling, J.] Duke Univ, Sch Med, Univ Hosp, Alamance Reg Med Ctr, Durham, NC USA.
[Donovan, E. F.; Bridges, K.; Alexander, B.; Grisby, C.; Mersmann, M. W.; Mincey, H. L.; Hessling, J.] Durham Reg Hosp, Durham, NC USA.
[Goldberg, R. N.; Auten, K. J.; Fisher, K. A.; Foy, K. A.; Siaw, G.] Childrens Healthcare Atlanta, Atlanta, GA USA.
[Goldberg, R. N.; Auten, K. J.; Fisher, K. A.; Foy, K. A.; Siaw, G.] Grady Mem Hosp, Atlanta, GA USA.
[Goldberg, R. N.; Auten, K. J.; Fisher, K. A.; Foy, K. A.; Siaw, G.] Emory Crawford Long Hosp, Atlanta, GA USA.
[Archer, S. W.] Indiana Univ Hosp, Indianapolis, IN 46202 USA.
[Archer, S. W.] Methodist Hosp, Indianapolis, IN USA.
[Archer, S. W.] Riley Hosp Children, Indianapolis, IN USA.
[Archer, S. W.] Wishard Hlth Serv, Indianapolis, IN USA.
[Lemons, J. A.; Hamer, F.; Herron, D. E.; Miller, L. C.; Wilson, L. D.] NHLBI, Bethesda, MD 20892 USA.
[Cunningham, M.; Hastings, B. K.; Irene, A. R.; Auman, J. O'D.; Huitema, C. P.; Pickett, J. W., II; Wallace, D.; Zaterka-Baxter, K. M.] Stanford Univ, Lucile Packard Childrens Hosp, Palo Alto, CA 94304 USA.
[Stevenson, D. K.; Ball, M. B.; Proud, M. S.] Floating Hosp Children, Tufts Med Ctr, Boston, MA USA.
[Fiascone, J. M.; Furey, A.; MacKinnon, B. L.; Nylen, E.] Univ Alabama Birmingham Hlth Syst, Birmingham, AL USA.
[Fiascone, J. M.; Furey, A.; MacKinnon, B. L.; Nylen, E.] Childrens Hosp Alabama, Birmingham, AL USA.
[Collins, M. V.; Cosby, S. S.; Phillips, V. A.] Univ Calif San Diego, Med Ctr, San Diego, CA 92103 USA.
[Collins, M. V.; Cosby, S. S.; Phillips, V. A.] Sharp Mary Birch Hosp Women, San Diego, CA USA.
[Rasmussen, M. R.; Wozniak, P. R.; Arnell, K.; Bridge, R.; Demetrio, C.] Univ Iowa Childrens Hosp, Iowa City, IA USA.
[Widness, J. A.; Klein, J. M.; Johnson, K. J.] Univ Miami, Holtz Childrens Hosp, Miami, FL USA.
[Everett-Thomas, R.] Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA.
[Ohls, R. K.; Rohr, J.; Lacy, C. B.] Univ Rochester, Med Ctr, Golisano Childrens Hosp, Rochester, NY 14642 USA.
[Markowitz, G. D.; Reubens, L. J.; Burnell, E.] Univ Texas SW Med Ctr Dallas, Parkland Hlth & Hosp Syst, Dallas, TX 75390 USA.
[Markowitz, G. D.; Reubens, L. J.; Burnell, E.] Childrens Med Ctr, Dallas, TX 75235 USA.
[Rosenfeld, C. R.; Salhab, W. A.; Guzman, A.; Hensley, G.; Lepps, M. H.; Miller, N. A.; Allen, J.; Grau, L.; Martin, M.; Solis, A.; Vasil, D. M.; Wilder, K.] Univ Texas Hlth Sci Ctr, Houston Med Sch, Houston, TX USA.
[Rosenfeld, C. R.; Salhab, W. A.; Guzman, A.; Hensley, G.; Lepps, M. H.; Miller, N. A.; Allen, J.; Grau, L.; Martin, M.; Solis, A.; Vasil, D. M.; Wilder, K.] Childrens Mem Hermann Hosp, Houston, TX USA.
[Kennedy, K. A.; Tyson, J. E.; Harris, B. F.; Lis, A. E.; Martin, S.; McDavid, G. E.; Tate, P. L.; Wright, S. L.] Intermt Med Ctr, Salt Lake City, UT USA.
[Kennedy, K. A.; Tyson, J. E.; Harris, B. F.; Lis, A. E.; Martin, S.; McDavid, G. E.; Tate, P. L.; Wright, S. L.] LDS Hosp, Salt Lake City, UT USA.
[Martin, M.; Kennedy, K. A.; Tyson, J. E.; Harris, B. F.; Lis, A. E.; McDavid, G. E.; Tate, P. L.; Wright, S. L.] Primary Childrens Med Ctr, Salt Lake City, UT 84103 USA.
[Burnett, J.; Jensen, J. J.; Osborne, K. A.; Spencer, C.; Weaver-Lewis, K.] Wake Forest Univ, Baptist Med Ctr, Brenner Childrens Hosp, Winston Salem, NC 27109 USA.
[Burnett, J.; Jensen, J. J.; Osborne, K. A.; Spencer, C.; Weaver-Lewis, K.] Forsyth Med Ctr, Winston Salem, NC USA.
[Peters, N. J.] Wayne State Univ, Hutzel Womens Hosp, Detroit, MI USA.
[Peters, N. J.] Childrens Hosp Michigan, Detroit, MI 48201 USA.
[Shankaran, S.; Bara, R.; Billian, E.; Johnson, M.] Yale New Haven Childrens Hosp, New Haven, CT USA.
[Shankaran, S.; Bara, R.; Billian, E.; Johnson, M.] Bridgeport Hosp, Bridgeport, CT USA.
[Avery, G.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Gleason, C. A.] Univ Washington, Seattle, WA 98195 USA.
[Allen, M. C.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Bangdiwala, S. I.] Univ N Carolina, Chapel Hill, NC USA.
[Blaisdell, C. J.] NHLBI, Bethesda, MD 20892 USA.
[Boyle, R. J.] Univ Virginia Hlth Syst, Charlottesville, VA USA.
[Clemons, T.] EMMES Corp, Baltimore, MD USA.
[D'Alton, M. E.] Columbia Univ, New York, NY USA.
[Keszler, M.] Georgetown Univ Hosp, Washington, DC 20007 USA.
[Redmond, C. K.] Univ Pittsburgh, Pittsburgh, PA USA.
[Ross, M. G.] Univ Calif Los Angeles, Sch Med & Publ Hlth, Los Angeles, CA USA.
[Thomson, M. A.] Hammersmith Hosp, London, England.
[Weiner, S. J.] George Washington Univ, Washington, DC USA.
[Markowitz, G. D.] Univ Rochester, Rochester, NY USA.
[Hutchinson, A. K.] Emory Univ, Atlanta, GA 30322 USA.
[Wallace, D. K.; Freedman, S. F.] Duke Univ, Durham, NC USA.
RP Carlo, WA (reprint author), Univ Alabama, Div Neonatol, 176F Suite 9380,619 S 19th St, Birmingham, AL 35294 USA.
EM wcarlo@peds.uab.edu
OI Ambalavanan, Namasivayam/0000-0003-0731-9092
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [U10 HD21364, U10 HD21373, U10 HD21385, U10 HD21397, U10
HD27851, U10 HD27853, U10 HD27856, U10 HD27880, U10 HD27871, U10
HD27904, U10 HD34216, U10 HD36790, U10 HD40461, U10 HD40492, U10
HD40498, U10 HD40521, U10 HD40689, U10 HD53089, U10 HD53109, U10
HD53119, U10 HD53124]; National Heart, Lung, and Blood Institute;
National Institutes of Health [M01 RR30, M01 RR32, M01 RR39, M01 RR44,
M01 RR54, M01 RR59, M01 RR64, M01 RR70, M01 RR80, MO1 RR125, M01 RR633,
M01 RR750, M01 RR997, M01 RR6022, M01 RR7122, M01 RR8084, M01 RR16587,
UL1 RR25008, UL1 RR24139, UL1 RR24979, UL1 RR25744]
FX Supported by grants (U10 HD21364, U10 HD21373, U10 HD21385, U10 HD21397,
U10 HD27851, U10 HD27853, U10 HD27856, U10 HD27880, U10 HD27871, U10
HD27904, U10 HD34216, U10 HD36790, U10 HD40461, U10 HD40492, U10
HD40498, U10 HD40521, U10 HD40689, U10 HD53089, U10 HD53109, U10
HD53119, and U10 HD53124) from the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, cofunding from the
National Heart, Lung, and Blood Institute, and grants (M01 RR30, M01
RR32, M01 RR39, M01 RR44, M01 RR54, M01 RR59, M01 RR64, M01 RR70, M01
RR80, MO1 RR125, M01 RR633, M01 RR750, M01 RR997, M01 RR6022, M01
RR7122, M01 RR8084, M01 RR16587, UL1 RR25008, UL1 RR24139, UL1 RR24979,
and UL1 RR25744) from the National Institutes of Health.
NR 25
TC 326
Z9 339
U1 2
U2 25
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAY 27
PY 2010
VL 362
IS 21
BP 1959
EP 1969
DI 10.1056/NEJMoa0911781
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 601JI
UT WOS:000278054000004
ER
PT J
AU Finer, NN
Carlo, WA
Walsh, MC
Rich, W
Gantz, MG
Laptook, AR
Yoder, BA
Faix, RG
Das, A
Poole, WK
Donovan, EF
Newman, NS
Ambalavanan, N
Frantz, ID
Buchter, S
Sanchez, PJ
Kennedy, KA
Laroia, N
Poindexter, BB
Cotten, CM
Van Meurs, KP
Duara, S
Narendran, V
Sood, BG
O'Shea, TM
Bell, EF
Bhandari, V
Watterberg, KL
Higgins, RD
AF Finer, Neil N.
Carlo, Waldemar A.
Walsh, Michele C.
Rich, Wade
Gantz, Marie G.
Laptook, Abbot R.
Yoder, Bradley A.
Faix, Roger G.
Das, Abhik
Poole, W. Kenneth
Donovan, Edward F.
Newman, Nancy S.
Ambalavanan, Namasivayam
Frantz, Ivan D., III
Buchter, Susie
Sanchez, Pablo J.
Kennedy, Kathleen A.
Laroia, Nirupama
Poindexter, Brenda B.
Cotten, C. Michael
Van Meurs, Krisa P.
Duara, Shahnaz
Narendran, Vivek
Sood, Beena G.
O'Shea, T. Michael
Bell, Edward F.
Bhandari, Vineet
Watterberg, Kristi L.
Higgins, Rosemary D.
CA Eunice Kennedy Shriver NICHD
TI Early CPAP versus Surfactant in Extremely Preterm Infants.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID BIRTH-WEIGHT INFANTS; CHRONIC LUNG-DISEASE; DELIVERY ROOM; INTUBATION;
RATES; PRESSURE; TRIAL
AB Background: There are limited data to inform the choice between early treatment with continuous positive airway pressure (CPAP) and early surfactant treatment as the initial support for extremely-low-birth-weight infants.
Methods: We performed a randomized, multicenter trial, with a 2-by-2 factorial design, involving infants who were born between 24 weeks 0 days and 27 weeks 6 days of gestation. Infants were randomly assigned to intubation and surfactant treatment (within 1 hour after birth) or to CPAP treatment initiated in the delivery room, with subsequent use of a protocol-driven limited ventilation strategy. Infants were also randomly assigned to one of two target ranges of oxygen saturation. The primary outcome was death or bronchopulmonary dysplasia as defined by the requirement for supplemental oxygen at 36 weeks (with an attempt at withdrawal of supplemental oxygen in neonates who were receiving less than 30% oxygen).
Results: A total of 1316 infants were enrolled in the study. The rates of the primary outcome did not differ significantly between the CPAP group and the surfactant group (47.8% and 51.0%, respectively; relative risk with CPAP, 0.95; 95% confidence interval [CI], 0.85 to 1.05) after adjustment for gestational age, center, and familial clustering. The results were similar when bronchopulmonary dysplasia was defined according to the need for any supplemental oxygen at 36 weeks (rates of primary outcome, 48.7% and 54.1%, respectively; relative risk with CPAP, 0.91; 95% CI, 0.83 to 1.01). Infants who received CPAP treatment, as compared with infants who received surfactant treatment, less frequently required intubation or postnatal corticosteroids for bronchopulmonary dysplasia (P<0.001), required fewer days of mechanical ventilation (P=0.03), and were more likely to be alive and free from the need for mechanical ventilation by day 7 (P=0.01). The rates of other adverse neonatal outcomes did not differ significantly between the two groups.
Conclusions: The results of this study support consideration of CPAP as an alternative to intubation and surfactant in preterm infants. (ClinicalTrials.gov number, NCT00233324.)
N Engl J Med 2010;362:1970-9.
C1 [Finer, Neil N.; Rich, Wade] Univ Calif San Diego, Div Neonatol, San Diego, CA 92103 USA.
[Carlo, Waldemar A.; Ambalavanan, Namasivayam] Univ Alabama, Div Neonatol, Birmingham, AL USA.
[Walsh, Michele C.; Newman, Nancy S.] Case Western Reserve Univ, Dept Pediat, Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA.
[Gantz, Marie G.; Poole, W. Kenneth] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA.
[Cotten, C. Michael] Duke Univ, Dept Pediat, Durham, NC 27706 USA.
[O'Shea, T. Michael] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA.
[Laptook, Abbot R.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA.
[Yoder, Bradley A.; Faix, Roger G.] Univ Utah, Sch Med, Dept Pediat, Div Neonatol, Salt Lake City, UT USA.
[Das, Abhik] RTI Int, Stat & Epidemiol Unit, Rockville, MD USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Donovan, Edward F.; Narendran, Vivek] Univ Cincinnati, Dept Pediat, Cincinnati, OH 45221 USA.
[Frantz, Ivan D., III] Floating Hosp Children, Tufts Med Ctr, Div Newborn Med, Dept Pediat, Boston, MA USA.
[Sanchez, Pablo J.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA.
[Buchter, Susie] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA.
[Buchter, Susie] Childrens Healthcare Atlanta, Atlanta, GA USA.
[Kennedy, Kathleen A.] Univ Texas Med Sch Houston, Dept Pediat, Houston, TX USA.
[Laroia, Nirupama] Univ Rochester, Sch Med & Dent, Rochester, NY USA.
[Poindexter, Brenda B.] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN USA.
[Van Meurs, Krisa P.] Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA.
[Sood, Beena G.] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
[Duara, Shahnaz] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Bell, Edward F.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA.
[Bhandari, Vineet] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
[Watterberg, Kristi L.] Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA.
RP Finer, NN (reprint author), Univ Calif San Diego, Div Neonatol, 402 Dickinson St,MPF 1-140, San Diego, CA 92103 USA.
EM nfiner@ucsd.edu
OI Ambalavanan, Namasivayam/0000-0003-0731-9092
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [U10 HD21364, U10 HD21373, U10 HD21385, U10 HD21397, U10
HD27851, U10 HD27853, U10 HD27856, U10 HD27880, U10 HD27871, U10
HD27904, U10 HD34216, U10 HD36790, U10 HD40461, U10 HD40492, U10
HD40498, U10 HD40521, U10 HD40689, U10 HD53089, U10 HD53109, U10
HD53119, U10 HD53124]; National Heart, Lung, and Blood Institute;
National Institutes of Health [M01 RR30, M01 RR32, M01 RR39, M01 RR44,
M01 RR54, M01 RR59, M01 RR64, M01 RR70, M01 RR80, MO1 RR125, M01 RR633,
M01 RR750, M01 RR997, M01 RR6022, M01 RR7122, M01 RR8084, M01 RR16587,
UL1 RR25008, UL1 RR24139, UL1 RR24979, UL1 RR25744]
FX Supported by grants (U10 HD21364, U10 HD21373, U10 HD21385, U10 HD21397,
U10 HD27851, U10 HD27853, U10 HD27856, U10 HD27880, U10 HD27871, U10
HD27904, U10 HD34216, U10 HD36790, U10 HD40461, U10 HD40492, U10
HD40498, U10 HD40521, U10 HD40689, U10 HD53089, U10 HD53109, U10
HD53119, U10 HD53124) from the Eunice Kennedy Shriver National Institute
of Child Health and Human Development, cofunding from the National
Heart, Lung, and Blood Institute, and grants ( M01 RR30, M01 RR32, M01
RR39, M01 RR44, M01 RR54, M01 RR59, M01 RR64, M01 RR70, M01 RR80, MO1
RR125, M01 RR633, M01 RR750, M01 RR997, M01 RR6022, M01 RR7122, M01
RR8084, M01 RR16587, UL1 RR25008, UL1 RR24139, UL1 RR24979, UL1 RR25744)
from the National Institutes of Health.
NR 20
TC 358
Z9 376
U1 5
U2 27
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAY 27
PY 2010
VL 362
IS 21
BP 1970
EP 1979
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 601JI
UT WOS:000278054000005
ER
PT J
AU Ohye, RG
Sleeper, LA
Mahony, L
Newburger, JW
Pearson, GD
Lu, MM
Goldberg, CS
Tabbutt, S
Frommelt, PC
Ghanayem, NS
Laussen, PC
Rhodes, JF
Lewis, AB
Mital, S
Ravishankar, C
Williams, IA
Dunbar-Masterson, C
Atz, AM
Colan, S
Minich, LL
Pizarro, C
Kanter, KR
Jaggers, J
Jacobs, JP
Krawczeski, CD
Pike, N
McCrindle, BW
Virzi, L
Gaynor, JW
AF Ohye, Richard G.
Sleeper, Lynn A.
Mahony, Lynn
Newburger, Jane W.
Pearson, Gail D.
Lu, Minmin
Goldberg, Caren S.
Tabbutt, Sarah
Frommelt, Peter C.
Ghanayem, Nancy S.
Laussen, Peter C.
Rhodes, John F.
Lewis, Alan B.
Mital, Seema
Ravishankar, Chitra
Williams, Ismee A.
Dunbar-Masterson, Carolyn
Atz, Andrew M.
Colan, Steven
Minich, L. LuAnn
Pizarro, Christian
Kanter, Kirk R.
Jaggers, James
Jacobs, Jeffrey P.
Krawczeski, Catherine Dent
Pike, Nancy
McCrindle, Brian W.
Virzi, Lisa
Gaynor, J. William
CA Pediat Heart Network Investigators
TI Comparison of Shunt Types in the Norwood Procedure for Single-Ventricle
Lesions.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID PULMONARY-ARTERY CONDUIT; LEFT-HEART SYNDROME; BLALOCK-TAUSSIG SHUNT;
OPERATION; OUTCOMES; PALLIATION; EXPERIENCE; RECONSTRUCTION;
HEMODYNAMICS; CHILDREN
AB Background: The Norwood procedure with a modified Blalock-Taussig (MBT) shunt, the first palliative stage for single-ventricle lesions with systemic outflow obstruction, is associated with high mortality. The right ventricle-pulmonary artery (RVPA) shunt may improve coronary flow but requires a ventriculotomy. We compared the two shunts in infants with hypoplastic heart syndrome or related anomalies.
Methods: Infants undergoing the Norwood procedure were randomly assigned to the MBT shunt (275 infants) or the RVPA shunt (274 infants) at 15 North American centers. The primary outcome was death or cardiac transplantation 12 months after randomization. Secondary outcomes included unintended cardiovascular interventions and right ventricular size and function at 14 months and transplantation-free survival until the last subject reached 14 months of age.
Results: Transplantation-free survival 12 months after randomization was higher with the RVPA shunt than with the MBT shunt (74% vs. 64%, P=0.01). However, the RVPA shunt group had more unintended interventions (P=0.003) and complications (P=0.002). Right ventricular size and function at the age of 14 months and the rate of nonfatal serious adverse events at the age of 12 months were similar in the two groups. Data collected over a mean (+/-SD) follow-up period of 32+/-11 months showed a nonsignificant difference in transplantation-free survival between the two groups (P=0.06). On nonproportional-hazards analysis, the size of the treatment effect differed before and after 12 months (P=0.02).
Conclusions: In children undergoing the Norwood procedure, transplantation-free survival at 12 months was better with the RVPA shunt than with the MBT shunt. After 12 months, available data showed no significant difference in transplantation-free survival between the two groups. (ClinicalTrials.gov number, NCT00115934.)
N Engl J Med 2010;362:1980-92.
C1 [Ohye, Richard G.; Goldberg, Caren S.] Univ Michigan, Sch Med, Ann Arbor, MI USA.
[Sleeper, Lynn A.; Lu, Minmin; Virzi, Lisa] New England Res Inst, Watertown, MA 02172 USA.
[Mahony, Lynn] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Newburger, Jane W.; Laussen, Peter C.; Dunbar-Masterson, Carolyn; Colan, Steven] Childrens Hosp Boston, Boston, MA USA.
[Pearson, Gail D.] NHLBI, Bethesda, MD 20892 USA.
[Tabbutt, Sarah; Ravishankar, Chitra; Gaynor, J. William] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Frommelt, Peter C.; Ghanayem, Nancy S.] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA.
[Frommelt, Peter C.; Ghanayem, Nancy S.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
N Carolina Consortium Duke Univ, Durham, NC USA.
E Carolina Univ, Greenville, NC 27858 USA.
[Rhodes, John F.; Jaggers, James] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Lewis, Alan B.; Pike, Nancy] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
[Mital, Seema; McCrindle, Brian W.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Williams, Ismee A.] Childrens Hosp New York, New York, NY USA.
[Atz, Andrew M.] Med Univ S Carolina, Charleston, SC 29425 USA.
[Minich, L. LuAnn] Univ Utah, Salt Lake City, UT USA.
[Minich, L. LuAnn] Primary Childrens Med Ctr, Salt Lake City, UT 84103 USA.
[Pizarro, Christian] Nemours Cardiac Ctr, Wilmington, DE USA.
[Kanter, Kirk R.] Emory Univ, Atlanta, GA 30322 USA.
[Jacobs, Jeffrey P.] Congenital Heart Inst Florida, St Petersburg, FL USA.
[Krawczeski, Catherine Dent] Cincinnati Childrens Med Ctr, Cincinnati, OH USA.
RP Ohye, RG (reprint author), 5144 CVC,1500 E Med Ctr Dr,SPC 5864, Ann Arbor, MI 48109 USA.
EM ohye@umich.edu
RI gaynor, James william/E-5194-2013
OI gaynor, James william/0000-0001-7955-5604
FU National Heart, Lung, and Blood Institute [HL068269, HL068270, HL068279,
HL068281, HL068285, HL068288, HL068290, HL068292, HL085057]
FX Supported by grants (HL068269, HL068270, HL068279, HL068281, HL068285,
HL068288, HL068290, HL068292, and HL085057) from the National Heart,
Lung, and Blood Institute.
NR 26
TC 276
Z9 280
U1 2
U2 10
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAY 27
PY 2010
VL 362
IS 21
BP 1980
EP 1992
DI 10.1056/NEJMoa0912461
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA 601JI
UT WOS:000278054000006
PM 20505177
ER
PT J
AU Feero, WG
Guttmacher, AE
Collins, FS
AF Feero, W. Gregory
Guttmacher, Alan E.
Collins, Francis S.
TI Genomic Medicine: Genomic Medicine -- An Updated Primer.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Review
ID MOLECULAR-ORIGINS; SEQUENCE; CANCER; EPIGENETICS; SIGNATURES; EVOLUTION;
DISEASES; PROJECT; BIOLOGY; GENES
C1 [Feero, W. Gregory] NHGRI, NIH, Bethesda, MD 20892 USA.
[Guttmacher, Alan E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Collins, Francis S.] NIH, Off Director, Bethesda, MD 20892 USA.
[Feero, W. Gregory] Maine Dartmouth Family Med Residency Program, Augusta, GA USA.
RP Feero, WG (reprint author), NHGRI, NIH, Bldg 31,Rm 4B09,31 Ctr Dr, Bethesda, MD 20892 USA.
EM feerow@mail.nih.gov
NR 50
TC 194
Z9 200
U1 5
U2 43
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAY 27
PY 2010
VL 362
IS 21
BP 2001
EP 2011
DI 10.1056/NEJMra0907175
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 601JI
UT WOS:000278054000008
PM 20505179
ER
PT J
AU Bondy, CA
AF Bondy, Carolyn A.
TI Hypoplastic Left Heart Syndrome.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID PALLIATION; NORWOOD
C1 NICHD, Program Dev Endocrinol & Genet, Bethesda, MD USA.
RP Bondy, CA (reprint author), NICHD, Program Dev Endocrinol & Genet, Bethesda, MD USA.
NR 11
TC 2
Z9 3
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAY 27
PY 2010
VL 362
IS 21
BP 2026
EP 2028
DI 10.1056/NEJMe1002923
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 601JI
UT WOS:000278054000013
PM 20505182
ER
PT J
AU Knerr, S
Ramos, E
Nowinski, J
Dixon, K
Bonham, VL
AF Knerr, Sarah
Ramos, Edward
Nowinski, Juleigh
Dixon, Keianna
Bonham, Vence L.
TI Human difference in the genomic era: Facilitating a socially responsible
dialogue
SO BMC MEDICAL GENOMICS
LA English
DT Article
ID ONGOING ADAPTIVE EVOLUTION; WIDE ASSOCIATION; BRAIN SIZE; HYPERTENSION;
RACE; MICROCEPHALIN; SLAVERY; ASPM; GENE; SUSCEPTIBILITY
AB Background: The study of human genetic variation has been advanced by research such as genome-wide association studies, which aim to identify variants associated with common, complex diseases and traits. Significant strides have already been made in gleaning information on susceptibility, treatment, and prevention of a number of disorders. However, as genetic researchers continue to uncover underlying differences between individuals, there is growing concern that observed population-level differences will be inappropriately generalized as inherent to particular racial or ethnic groups and potentially perpetuate negative stereotypes.
Discussion: We caution that imprecision of language when conveying research conclusions, compounded by the potential distortion of findings by the media, can lead to the stigmatization of racial and ethnic groups.
Summary: It is essential that the scientific community and with those reporting and disseminating research findings continue to foster a socially responsible dialogue about genetic variation and human difference.
C1 [Knerr, Sarah; Ramos, Edward; Nowinski, Juleigh; Dixon, Keianna; Bonham, Vence L.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Ramos, Edward] NIH, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA.
[Knerr, Sarah] Univ Washington, Inst Publ Hlth Genet, Seattle, WA 98195 USA.
[Nowinski, Juleigh] Off Assistant Secretary Hlth, Dept Hlth & Human Serv, Washington, DC 20201 USA.
[Dixon, Keianna] Columbia Univ, New York, NY 10027 USA.
RP Ramos, E (reprint author), NHGRI, NIH, 31 Ctr Dr, Bethesda, MD 20892 USA.
EM ramose@mail.nih.gov
FU National Human Genome Research Institute, National Institutes of Health
FX The development of this manuscript was supported by the Intramural
Research Program of the National Human Genome Research Institute,
National Institutes of Health. We also thank the reviewers for their
helpful suggestions, which substantially improved the article. The
content is solely the responsibility of the authors and does not
represent the official position of the National Human Genome Research
Institute, National Institutes of Health or the Department of Health and
Human Services.
NR 46
TC 4
Z9 4
U1 1
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1755-8794
J9 BMC MED GENOMICS
JI BMC Med. Genomics
PD MAY 26
PY 2010
VL 3
AR 20
DI 10.1186/1755-8794-3-20
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA 625RM
UT WOS:000279912700001
PM 20504336
ER
PT J
AU Sharon, E
Kelly, RJ
Szabo, E
AF Sharon, Elad
Kelly, Ronan J.
Szabo, Eva
TI Sustained response of carcinoma ex pleomorphic adenoma treated with
trastuzumab and capecitabine
SO HEAD & NECK ONCOLOGY
LA English
DT Article
ID PHASE-II; SALIVARY; THERAPY; GLANDS
AB Background: Carcinoma ex pleomorphic adenoma is a rare histologic subtype of salivary gland cancer with an overall poor prognosis. Limited histopathologic analyses have shown that some such tumors exhibit significant HER2/neu immunoreactivity, suggesting a potential role for HER2-based therapy. We report here a case of a 58-year old man with metastatic carcinoma ex pleomorphic adenoma who achieved a sustained long term response to combination therapy with trastuzumab and capecitabine.
Case presentation: A 58 year old man presented with T1N2bM0 carcinoma ex pleomorphic adenoma and underwent surgery followed by adjuvant radiation therapy. Multiple metastases to bone were documented one year later. Since the original tumor was strongly HER2/neu positive by immunohistochemistry, the patient was treated with trastuzumab, capecitabine, and zoledronic acid. He experienced total resolution of symptoms and repeat FDG-PET scan after three cycles revealed interval disease resolution. Continued treatment has resulted in maintenance of disease control for over 2 years.
Conclusion: This case illustrates the successful long term treatment of carcinoma ex pleomorphic adenoma with targeted therapy with trastuzumab in combination with chemotherapy. In the absence of definitive clinical trials which are unlikely to be performed due to the rarity of this tumor, case reports such as this one suggest potential utility for trastuzumab in combination with chemotherapy in the treatment of HER2/neu-overexpressing carcinoma ex pleomorphic adenoma.
C1 [Szabo, Eva] NCI, Lung & Upper Aerodigest Canc Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Sharon, Elad; Kelly, Ronan J.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Szabo, E (reprint author), NCI, Lung & Upper Aerodigest Canc Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
EM szaboe@mail.nih.gov
NR 11
TC 12
Z9 12
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1758-3284
J9 HEAD NECK ONCOL
JI Head Neck Oncol.
PD MAY 26
PY 2010
VL 2
AR 12
DI 10.1186/1758-3284-2-12
PG 3
WC Oncology
SC Oncology
GA 840IK
UT WOS:000296432900001
PM 20504363
ER
PT J
AU Piekarz, R
Zivotofsky, AZ
AF Piekarz, Richard
Zivotofsky, Ari Z.
TI Religious Tradition and Concern for the Welfare of All Living Beings
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
C1 [Piekarz, Richard] NCI, Canc Therapy Evaluat Program, Rockville, MD USA.
[Zivotofsky, Ari Z.] Bar Ilan Univ, Neurosci Program, Ramat Gan, Israel.
RP Piekarz, R (reprint author), NCI, Canc Therapy Evaluat Program, Rockville, MD USA.
EM zivotoa@mail.biu.ac.il
NR 1
TC 0
Z9 0
U1 0
U2 1
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 MAY 26
PY 2010
VL 303
IS 20
BP 2033
EP 2034
DI 10.1001/jama.2010.664
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 600VY
UT WOS:000278018200020
PM 20501923
ER
PT J
AU Androutsellis-Theotokis, A
Walbridge, S
Park, DM
Lonser, RR
Mckay, RDG
AF Androutsellis-Theotokis, Andreas
Walbridge, Stuart
Park, Deric M.
Lonser, Russell R.
McKay, Ronald D. G.
TI Cholera Toxin Regulates a Signaling Pathway Critical for the Expansion
of Neural Stem Cell Cultures from the Fetal and Adult Rodent Brains
SO PLOS ONE
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; SUBVENTRICULAR ZONE; IN-VIVO; DENTATE GYRUS;
PROGENITOR PROLIFERATION; MOUSE BRAIN; NEUROGENESIS; NEURONS;
DIFFERENTIATION; RAT
AB Background: New mechanisms that regulate neural stem cell (NSC) expansion will contribute to improved assay systems and the emerging regenerative approach that targets endogenous stem cells. Expanding knowledge on the control of stem cell self renewal will also lead to new approaches for targeting the stem cell population of cancers.
Methodology/Principal Findings: Here we show that Cholera toxin regulates two recently characterized NSC markers, the Tie2 receptor and the transcription factor Hes3, and promotes the expansion of NSCs in culture. Cholera toxin increases immunoreactivity for the Tie2 receptor and rapidly induces the nuclear localization of Hes3. This is followed by powerful cultured NSC expansion and induction of proliferation both in the presence and absence of mitogen.
Conclusions/Significance: Our data suggest a new cell biological mechanism that regulates the self renewal and differentiation properties of stem cells, providing a new logic to manipulate NSCs in the context of regenerative disease and cancer.
C1 [Androutsellis-Theotokis, Andreas; Park, Deric M.; McKay, Ronald D. G.] NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Walbridge, Stuart; Lonser, Russell R.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
RP Androutsellis-Theotokis, A (reprint author), Acad Athens, Biomed Res Fdn, Athens, Greece.
EM AndreasTheotokis@gmail.com
RI Park, Deric/C-5675-2013
FU National Institute of Neurological Disorders and Stroke; Michael J. Fox
Foundation; National Parkinson's Foundation; Tuchman Foundation
FX This work was supported by the Intramural Research Program of the
National Institute of Neurological Disorders and Stroke at the National
Institutes of Health, and by additional support from the Michael J. Fox
Foundation, the National Parkinson's Foundation, and the Tuchman
Foundation. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 36
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Z9 14
U1 1
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 MAY 26
PY 2010
VL 5
IS 5
AR e10841
DI 10.1371/journal.pone.0010841
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 603PW
UT WOS:000278221500027
PM 20520777
ER
PT J
AU Pavlicek, J
Sauzet, S
Besseau, L
Coon, SL
Weller, JL
Boeuf, G
Gaildrat, P
Omelchenko, MV
Koonin, EV
Falcon, J
Klein, DC
AF Pavlicek, Jiri
Sauzet, Sandrine
Besseau, Laurence
Coon, Steven L.
Weller, Joan L.
Boeuf, Gilles
Gaildrat, Pascaline
Omelchenko, Marina V.
Koonin, Eugene V.
Falcon, Jack
Klein, David C.
TI Evolution of AANAT: expansion of the gene family in the cephalochordate
amphioxus
SO BMC EVOLUTIONARY BIOLOGY
LA English
DT Article
ID ARYLALKYLAMINE N-ACETYLTRANSFERASE; AMINO-ACID SUBSTITUTION; MULTIPLE
SEQUENCE ALIGNMENT; MELATONIN RHYTHM ENZYME; BRANCHIOSTOMA-LANCEOLATUM;
PINEAL ORGAN; EC 2.3.1.87; PROTEIN SEQUENCES; TROUT RETINA; SEROTONIN
AB Background: The arylalkylamine N-acetyltransferase (AANAT) family is divided into structurally distinct vertebrate and non-vertebrate groups. Expression of vertebrate AANATs is limited primarily to the pineal gland and retina, where it plays a role in controlling the circadian rhythm in melatonin synthesis. Based on the role melatonin plays in biological timing, AANAT has been given the moniker "the Timezyme". Non-vertebrate AANATs, which occur in fungi and protists, are thought to play a role in detoxification and are not known to be associated with a specific tissue.
Results: We have found that the amphioxus genome contains seven AANATs, all having non-vertebrate type features. This and the absence of AANATs from the genomes of Hemichordates and Urochordates support the view that a major transition in the evolution of the AANATs may have occurred at the onset of vertebrate evolution. Analysis of the expression pattern of the two most structurally divergent AANATs in Branchiostoma lanceolatum (bl) revealed that they are expressed early in development and also in the adult at low levels throughout the body, possibly associated with the neural tube. Expression is clearly not exclusively associated with the proposed analogs of the pineal gland and retina. blAANAT activity is influenced by environmental lighting, but light/dark differences do not persist under constant light or constant dark conditions, indicating they are not circadian in nature. bfAANAT alpha and bfAANAT delta' have unusually alkaline (>9.0) optimal pH, more than two pH units higher than that of vertebrate AANATs.
Conclusions: The substrate selectivity profiles of bfAANAT alpha and delta' are relatively broad, including alkylamines, arylalkylamines and diamines, in contrast to vertebrate forms, which selectively acetylate serotonin and other arylalkylamines. Based on these features, it appears that amphioxus AANATs could play several roles, including detoxification and biogenic amine inactivation. The presence of seven AANATs in amphioxus genome supports the view that arylalkylamine and polyamine acetylation is important to the biology of this organism and that these genes evolved in response to specific pressures related to requirements for amine acetylation.
C1 [Pavlicek, Jiri; Coon, Steven L.; Weller, Joan L.; Gaildrat, Pascaline; Klein, David C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Neuroendocrinol, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
[Sauzet, Sandrine; Besseau, Laurence; Boeuf, Gilles; Falcon, Jack] UPMC Paris 6, Lab Arago, F-66651 Banyuls Sur Mer, France.
[Sauzet, Sandrine; Besseau, Laurence; Boeuf, Gilles; Falcon, Jack] CNRS, FRE 3247, F-66651 Banyuls Sur Mer, France.
[Sauzet, Sandrine; Besseau, Laurence; Boeuf, Gilles; Falcon, Jack] CNRS, GDR 2821, F-66651 Banyuls Sur Mer, France.
[Boeuf, Gilles] Museum Natl Hist Nat, F-75005 Paris, France.
[Omelchenko, Marina V.; Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Klein, DC (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Neuroendocrinol, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
EM kleind@mail.nih.gov
RI FALCON, Jack/I-5302-2013; Pavlicek, Jiri/G-9927-2014; Besseau,
Laurence/O-9942-2015
OI FALCON, Jack/0000-0002-7572-6581; Besseau, Laurence/0000-0002-9617-8190
FU NICHD, National Institutes of Health; CNRS; UPMC; French National
Research Agency [ANR-07-BLAN0097]
FX This work was supported by the NIH Intramural Research Program through
the NICHD, National Institutes of Health. 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. Work was also
supported by the CNRS, UPMC and the French National Research Agency
(project TEMPANAT, ANR-07-BLAN0097). We are grateful to Dr. Dan L.
Sackett for help with fluorescence measurement and Drs. Howard Jaffe and
Sam J. Clokie for help with the MALDI-TOF analysis of protein samples.
NR 50
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U1 0
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2148
J9 BMC EVOL BIOL
JI BMC Evol. Biol.
PD MAY 25
PY 2010
VL 10
AR 154
DI 10.1186/1471-2148-10-154
PG 15
WC Evolutionary Biology; Genetics & Heredity
SC Evolutionary Biology; Genetics & Heredity
GA 624OP
UT WOS:000279828900001
PM 20500864
ER
PT J
AU Duhagon, MA
Hurt, EM
Sotelo-Silveira, JR
Zhang, XH
Farrar, WL
AF Duhagon, Maria Ana
Hurt, Elaine M.
Sotelo-Silveira, Jose R.
Zhang, Xiaohu
Farrar, William L.
TI Genomic profiling of tumor initiating prostatospheres
SO BMC GENOMICS
LA English
DT Article
ID CANCER STEM-CELLS; PROSTATE-CANCER; GENE-EXPRESSION; SIGNALING PATHWAYS;
EPITHELIAL-CELLS; SELF-RENEWAL; IN-VITRO; NOTCH; PROGRESSION; BREAST
AB Background: The cancer stem cell (CSC) hypothesis proposes that a population of tumor cells bearing stem cell properties is responsible for the origin and maintenance of tumors. Normal and cancer stem cells possess the ability to grow in vitro as self-renewing spheres, but the molecular basis of this phenotype remains largely unknown. We intended to establish a comprehensive culture system to grow prostatospheres (PSs) from both cancer cell lines and patient tumors. We then used gene expression microarrays to gain insight on the molecular pathways that sustain the PS tumor initiating cell (TIC) phenotype.
Results: Traditional stem cell medium (SCM) supplemented with Knockout(TM) SR (KO) allows the propagation of monoclonal PSs from cell lines and primary cells. PSs display gene expression and tumorigenicity hallmarks of TICs. Gene expression analysis defined a gene signature composed of 66 genes that characterize LNCaP and patient PSs. This set includes novel prostate TIC growth factors (NRP1, GDF1, JAG1), proteins implicated in cell adhesion and cytoskeletal maintenance, transcriptional regulators (MYCBP, MYBL1, ID1, ID3, FOS, ELF3, ELF4, KLF2, KLF5) and factors involved in protein biosynthesis and metabolism. Meta-analysis in Oncomine reveals that some of these genes correlate with prostate cancer status and/or progression. Reporter genes and inhibitors indicate that the Notch pathway contributes to prostatosphere growth.
Conclusions: We have developed a model for the culture of PSs, and provide a genomic profile that support CSCs identity. This signature identifies novel markers and pathways that are predicted to correlate with prostate cancer evolution.
C1 [Duhagon, Maria Ana; Hurt, Elaine M.; Zhang, Xiaohu; Farrar, William L.] NCI, Canc Stem Cell Sect, Lab Canc Prevent, Frederick, MD 21702 USA.
[Duhagon, Maria Ana] Univ Republica, Fac Ciencias, Dept Biol Mol & Celular, Lab Interacc Mol, Montevideo 11400, Uruguay.
[Duhagon, Maria Ana] Univ Republica, Fac Med, Dept Genet, Montevideo 11800, Uruguay.
[Sotelo-Silveira, Jose R.] NCI, Lab Mol Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Sotelo-Silveira, Jose R.] Inst Invest Biol Clemente Estable, Dept Neurobiol Mol & Celular, Montevideo 11600, Uruguay.
RP Duhagon, MA (reprint author), NCI, Canc Stem Cell Sect, Lab Canc Prevent, 1050 Boyles St, Frederick, MD 21702 USA.
EM mduhagon@fcien.edu.uy
FU National Cancer Institute, National Institutes of Health [N01-CO-12400];
NIH, National Cancer Institute, Center for Cancer Research
FX We would like to acknowledge Dr. Robert H. Shoemaker and Karen Hite for
kindly sharing the GelCount Scanner used for the quantization of PSs.
This publication has been funded in part with Federal funds from the
National Cancer Institute, National Institutes of Health, under contract
No. N01-CO-12400. This research was supported in part by the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U. S. Government.
NR 64
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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 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD MAY 25
PY 2010
VL 11
AR 324
DI 10.1186/1471-2164-11-324
PG 16
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 625AM
UT WOS:000279863700001
PM 20500816
ER
PT J
AU Salcido, CD
Larochelle, A
Taylor, BJ
Dunbar, CE
Varticovski, L
AF Salcido, C. D.
Larochelle, A.
Taylor, B. J.
Dunbar, C. E.
Varticovski, L.
TI Molecular characterisation of side population cells with cancer stem
cell-like characteristics in small-cell lung cancer
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE angiogenesis; drug resistance; gene expression; xenograft
ID BREAST-CANCER; PROSPECTIVE IDENTIFICATION; MULTIDRUG-RESISTANCE;
GENE-EXPRESSION; TUMOR-GROWTH; IN-VITRO; PROGENITORS; ABCG2; VIVO
AB BACKGROUND: Side population (SP) fraction cells, identified by efflux of Hoechst dye, are present in virtually all normal and malignant tissues. The relationship between SP cells, drug resistance and cancer stem cells is poorly understood. Small-cell lung cancer (SCLC) is a highly aggressive human tumour with a 5-year survival rate of < 10%. These features suggest enrichment in cancer stem cells.
METHODS AND RESULTS: We examined several SCLC cell lines and found that they contain a consistent SP fraction that comprises < 1% of the bulk population. Side population cells have higher proliferative capacity in vitro, efficient self-renewal and reduced cell surface expression of neuronal differentiation markers, CD56 and CD90, as compared with non-SP cells. Previous reports indicated that several thousand SP cells from non-small-cell lung cancer are required to form tumours in mice. In contrast, as few as 50 SP cells from H146 and H526 SCLC cell lines rapidly reconstituted tumours. Whereas non-SP cells formed fewer and slower-growing tumours, SP cells over-expressed many genes associated with cancer stem cell and drug resistance: ABCG2, FGF1, IGF1, MYC, SOX1/2, WNT1, as well as genes involved in angiogenesis, Notch and Hedgehog pathways.
CONCLUSIONS: Side population cells from SCLC are highly enriched in tumourigenic cells and are characterised by a specific stem cell-associated gene expression signature. This gene signature may be used for development of targeted therapies for this rapidly fatal tumour. British Journal of Cancer (2010) 102, 1636-1644. doi:10.1038/sj.bjc.6605668 www.bjcancer.com Published online 27 April 2010 (C) 2010 Cancer Research UK
C1 [Salcido, C. D.; Varticovski, L.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Salcido, C. D.] Albert Einstein Coll Med, Bronx, NY 10461 USA.
[Larochelle, A.; Dunbar, C. E.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA.
[Taylor, B. J.] NCI, Flow Cytometry Core Facil, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Varticovski, L (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM varticol@mail.nih.gov
FU National Cancer Institute; National Heart, Lung and Blood Institute
FX We thank C Harris, S Pine, B Ryan and A Robles for their help in
performance of some experiments and for their constructive suggestions.
This work was supported by the intramural program at the National Cancer
Institute (CS, BT, LV), and at the National Heart, Lung and Blood
Institute (AL, CD).
NR 38
TC 78
Z9 86
U1 0
U2 15
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 MAY 25
PY 2010
VL 102
IS 11
BP 1636
EP 1644
DI 10.1038/sj.bjc.6605668
PG 9
WC Oncology
SC Oncology
GA 602IR
UT WOS:000278133200009
PM 20424609
ER
PT J
AU Karami, S
Schwartz, K
Purdue, MP
Davis, FG
Ruterbusch, JJ
Munuo, SS
Wacholder, S
Graubard, BI
Colt, JS
Chow, WH
AF Karami, S.
Schwartz, K.
Purdue, M. P.
Davis, F. G.
Ruterbusch, J. J.
Munuo, S. S.
Wacholder, S.
Graubard, B. I.
Colt, J. S.
Chow, W-H
TI Family history of cancer and renal cell cancer risk in Caucasians and
African Americans
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE renal cancer; kidney cancer; family history of cancer; race; Blacks
ID KIDNEY-CANCER; CARCINOMA; DENMARK; SWEDEN; TUMORS
AB BACKGROUND: The association between renal cell carcinoma (RCC) risk and family history of cancer has not been examined with an adequate number of African Americans (AAs).
METHODS: In a population-based case-control study, unconditional logistic regression was used to calculate the association between RCC risk and a family history of cancer among 1217 RCC cases and 1235 controls.
RESULTS: Increased RCC risk was shown for subjects with at least one first-degree relative with kidney cancer (odds ratio 2.29; 95% confidence interval 1.31-4.00). No differences in risk were observed when analyses were stratified by race. For Caucasians, excess risk was observed among those reporting a sibling with kidney cancer, whereas for AAs, increased risk occurred among subjects reporting either a sibling or parent affected with the disease. A family history of non-renal cancers, and those related to smoking or to the von Hippel-Lindau syndrome, revealed no association with RCC risk.
CONCLUSION: The RCC risk associated with a family history of kidney cancer is similar among Caucasians and AAs. British Journal of Cancer (2010) 102, 1676-1680. doi:10.1038/sj.bjc.6605680 www.bjcancer.com Published online 4 May 2010 (C) 2010 Cancer Research UK
C1 [Karami, S.; Purdue, M. P.; Wacholder, S.; Graubard, B. I.; Colt, J. S.; Chow, W-H] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Schwartz, K.; Ruterbusch, J. J.] Wayne State Univ, Karmanos Canc Inst, Dept Family Med, Detroit, MI 48201 USA.
[Schwartz, K.; Ruterbusch, J. J.] Wayne State Univ, Karmanos Canc Inst, Dept Publ Hlth Sci, Detroit, MI 48201 USA.
[Schwartz, K.; Ruterbusch, J. J.] Wayne State Univ, Populat Studies & Prevent Program, Detroit, MI 48201 USA.
[Davis, F. G.] Univ Illinois, Sch Publ Hlth, Div Epidemiol & Biostat, Chicago, IL 60612 USA.
[Munuo, S. S.] Informat Management Serv Inc, Rockville, MD 20852 USA.
RP Karami, S (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,MSC 7242, Bethesda, MD 20892 USA.
EM karamis@mail.nih.gov
RI Purdue, Mark/C-9228-2016
OI Purdue, Mark/0000-0003-1177-3108
NR 23
TC 10
Z9 10
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD MAY 25
PY 2010
VL 102
IS 11
BP 1676
EP 1680
DI 10.1038/sj.bjc.6605680
PG 5
WC Oncology
SC Oncology
GA 602IR
UT WOS:000278133200016
PM 20442711
ER
PT J
AU Alptekin, A
Galadari, S
Shuba, Y
Petroianu, G
Oz, M
AF Alptekin, Alp
Galadari, Sehammuddin
Shuba, Yaroslav
Petroianu, Georg
Oz, Murat
TI The effects of anandamide transport inhibitor AM404 on voltage-dependent
calcium channels
SO EUROPEAN JOURNAL OF PHARMACOLOGY
LA English
DT Article
DE Calcium channel; AM404; Endocannabinoid; Skeletal muscle
ID SKELETAL-MUSCLE CELLS; T-TUBULE MEMBRANES; ENDOGENOUS CANNABINOID
ANANDAMIDE; ION CHANNELS; CA2+ FLUXES; RECEPTORS; ENDOCANNABINOIDS;
CULTURE; PHARMACOLOGY; SELECTIVITY
AB The effects of anandamide transport inhibitor AM404 were investigated on depolarization-induced (45)Ca(2+) fluxes in transverse tubule membrane vesicles from rabbit skeletal muscle and on Ba2+ currents through L-type voltage-dependent Ca(2+) channels in rat myotubes. AM404, at the concentration of 3 mu M and higher, caused a significant inhibition of (45)Ca(2+) fluxes. Radioligand binding studies indicated that the specific binding of [(3)H] Isradipine to transverse tubule membranes was also inhibited significantly by AM404. In controls and in presence of 10 mu M AM404, B(max) values were 51 +/- 6 and 27 +/- 5 pM/mg, and KD values were 236 +/- 43 and 220 +/- 37 pM, respectively. Inhibitory effects of AEA and arachidonic add on (45)Ca(2+) flux and [(3)H]Isradipine binding reported in earlier studies, were also enhanced significantly in the presence of AM404. In the presence of VDM11 (1 mu M), another anandamide transport inhibitor. AM404 continued to inhibit (45)Ca(2+) fluxes and [(3)H]Isradipine binding. In rat myotubes, Ca(2+) currents through L-type Ca(2+) channels recorded in whole-cell configuration of patch clamp technique were inhibited by AM404 in a concentration-dependent manner with an IC(50) value of 3.2 mu M. In conclusion, results indicate that AM404 inhibits directly the function of L-type voltage-dependent Ca(2+) channels in mammalian skeletal muscles. Published by Elsevier B.V.
C1 [Oz, Murat] NIDA, IRP, Integrat Neurosci Sect, Baltimore, MD 21224 USA.
[Alptekin, Alp] Yildirim Beyazit Training & Res Hosp, Dept Anesthesiol, TR-06270 Ankara, Turkey.
[Galadari, Sehammuddin] UAE Univ, Fac Med & Hlth Sci, Dept Biochem, Al Ain, U Arab Emirates.
[Shuba, Yaroslav] Natl Acad Sci Ukraine, Bogomoletz Inst Physiol, Kiev 24, Ukraine.
[Shuba, Yaroslav] Natl Acad Sci Ukraine, Int Ctr Mol Physiol, Kiev 24, Ukraine.
[Petroianu, Georg; Oz, Murat] UAE Univ, Dept Pharmacol, Fac Med & Hlth Sci, Al Ain, U Arab Emirates.
RP Oz, M (reprint author), NIDA, IRP, Integrat Neurosci Sect, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM moz@intra.nida.nih.gov
RI Oz, Murat/E-2148-2012
FU NIDA/NIH, USA; United Arab Emirates University
FX This study was in part supported by the Intramural Research Program of
the NIDA/NIH, USA and the United Arab Emirates University Research
Funds.
NR 32
TC 8
Z9 10
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-2999
J9 EUR J PHARMACOL
JI Eur. J. Pharmacol.
PD MAY 25
PY 2010
VL 634
IS 1-3
BP 10
EP 15
DI 10.1016/j.ejphar.2010.02.013
PG 6
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 594RK
UT WOS:000277554900002
PM 20171208
ER
PT J
AU Taes, I
Goris, A
Lemmens, R
van Es, MA
van den Berg, LH
Chio, A
Traynor, BJ
Birve, A
Andersen, P
Slowik, A
Tomik, B
Brown, RH
Shaw, CE
Al-Chalabi, A
Boonen, S
Van Den Bosch, L
Dubois, B
Van Damme, P
Robberecht, W
AF Taes, I.
Goris, A.
Lemmens, R.
van Es, M. A.
van den Berg, L. H.
Chio, A.
Traynor, B. J.
Birve, A.
Andersen, P.
Slowik, A.
Tomik, B.
Brown, R. H., Jr.
Shaw, C. E.
Al-Chalabi, A.
Boonen, S.
Van Den Bosch, L.
Dubois, B.
Van Damme, P.
Robberecht, W.
TI Tau levels do not influence human ALS or motor neuron degeneration in
the SOD1(G93A) mouse
SO NEUROLOGY
LA English
DT Article
ID AMYOTROPHIC-LATERAL-SCLEROSIS; PROGRESSIVE SUPRANUCLEAR PALSY;
FRONTOTEMPORAL DEMENTIA; ALZHEIMERS-DISEASE; ASSOCIATION ANALYSIS;
PARKINSONS-DISEASE; MAPT LOCUS; CORTICOBASAL DEGENERATION;
SUSCEPTIBILITY GENE; HAPLOTYPE
AB Background: The microtubule-associated protein tau is thought to play a pivotal role in neurodegeneration. Mutations in the tau coding gene MAPT are a cause of frontotemporal dementia, and the H1/H1 genotype of MAPT, giving rise to higher tau expression levels, is associated with progressive supranuclear palsy, corticobasal degeneration, and Parkinson disease (PD). Furthermore, tau hyperphosphorylation and aggregation is a hallmark of Alzheimer disease (AD), and reducing endogenous tau has been reported to ameliorate cognitive impairment in a mouse model for AD. Tau hyperphosphorylation and aggregation have also been described in amyotrophic lateral sclerosis (ALS), both in human patients and in the mutant SOD1 mouse model for this disease. However, the precise role of tau in motor neuron degeneration remains uncertain.
Methods: The possible association between ALS and the MAPT H1/H2 polymorphism was studied in 3,540 patients with ALS and 8,753 controls. Furthermore, the role of tau in the SOD1(G93A) mouse model for ALS was studied by deleting Mapt in this model.
Results: The MAPT genotype of the H1/H2 polymorphism did not influence ALS susceptibility (odds ratio = 1.08 [95% confidence interval 0.99-1.18], p = 0.08) and did not affect the clinical phenotype. Lowering tau levels in the SOD1(G93A) mouse failed to delay disease onset (p = 0.302) or to increase survival (p = 0.557).
Conclusion: These findings suggest that the H1/H2 polymorphism in MAPT is not associated with human amyotrophic lateral sclerosis, and that lowering tau levels in the mutant SOD1 mouse does not affect the motor neuron degeneration in these animals. Neurology (R) 2010; 74: 1687-1693
C1 [Taes, I.; Goris, A.; Lemmens, R.; Boonen, S.; Van Den Bosch, L.; Dubois, B.; Van Damme, P.; Robberecht, W.] Univ Leuven, Louvain, Belgium.
[van Es, M. A.; van den Berg, L. H.] Rudolf Magnus Inst Neurosci, NL-3508 TA Utrecht, Netherlands.
[Chio, A.] Univ Turin, I-10124 Turin, Italy.
[Traynor, B. J.] NIA, Bethesda, MD 20892 USA.
[Birve, A.; Andersen, P.] Umea Univ Hosp, S-90185 Umea, Sweden.
[Slowik, A.; Tomik, B.] Jagiellonian Univ, PL-31007 Krakow, Poland.
[Brown, R. H., Jr.] Univ Massachusetts, Med Ctr, Worcester, MA USA.
[Shaw, C. E.; Al-Chalabi, A.] MRC, Ctr Neurodegenerat Res, London, England.
RP Robberecht, W (reprint author), Katholieke Univ Leuven, Univ Hosp Gasthuisberg, Neurobiol Lab, Herestr 49, B-3000 Louvain, Belgium.
EM wim.robberecht@uz.kuleuven.be
RI Van Damme, Philip/A-6464-2009; Al-Chalabi, Ammar/E-5361-2010; Van Den
Bosch, Ludo/B-7258-2012; Traynor, Bryan/G-5690-2010; Goris,
An/F-2943-2010;
OI Van Damme, Philip/0000-0001-6384-0611; Al-Chalabi,
Ammar/0000-0002-4924-7712; Goris, An/0000-0002-1276-6682; Chio,
Adriano/0000-0001-9579-5341
FU University of Leuven [Z01 AG000949-02]; NINDS; NIMH; Packard Center for
ALS Research at Johns Hopkins; ALS Association; Belgian Federal Science
Policy Office [P6/43]; Prinses Beatrix Fonds; VSB Fonds; H. Kersten and
M. Kersten (Kersten Foundation); Netherlands ALS Foundation; J. R. van
Dijk; Adessium Foundation; Motor Neurone Disease Association of Great
Britain and Ireland; Medical Research Council (UK); E von Behring Chair
for Neuromuscular and Neurodegenerative Disorders; University of Leuven;
Agency for Innovation by Science and Technology in Flanders (IWT);
Wellcome Trust [076113]; Research Foundation Flanders (FWO-Vlaanderen);
Belgian Neurological Society; Baxter International Inc.; Ministero della
Salute; Regione Piemonte; Ministero dell'Universita e della Ricerca;
Universita di Torino; Fondazione Vialli and Mauro for ALS Research;
Federazione Italiana Giuoco Calcio; Max och Edit Follins Foundation;
Swedish Medical Research Council; Swedish Brain Research Foundation;
Swedish Brain Power Society; Swedish Medical Society; Swedish Patient
Organization; NIH (NINDS) [1RC1NS068391-01]; PI Hayward, Brown; NINDS
[1RC2NS070342-01, R01NS050557-05]; ALS Therapy Alliance; Angel Fund for
ALS Research; Pierre L. deBourgknecht ALS Research Fund; Day
Neuromuscular Research Foundation; AthenaGenica; Medical Research
Council UK; Motor Neuron Disease Association; Wellcome Trust; American
ALS Association; Angel Fund; Agency for Research on Amyotrophic Lateral
Sclerosis Italy (AriSLA); Fonds voor Wetenschappelijk Onderzoek
Vlaanderen (FWO-Vlaanderen); Association Belge contre les Maladies
neuro-Musculaires; Association Francaise contre les Myopathies; Bayer
Schering Pharma; Biogen Idec; Merck Serono; NeuroNova; Trophos; Teva
Pharmaceutical Industries Ltd.; Packard Center for ALS Research; Thierry
Latran Foundation; Fund for Scientific Research Flanders; Institute for
Innovation in Science and Technology Flanders; Flanders Institute for
Biotechnology; Packard Center at Johns Hopkins
FX Supported by the University of Leuven, intramural programs of the NIA
(Z01 AG000949-02), the NINDS, and the NIMH, the Packard Center for ALS
Research at Johns Hopkins, the ALS Association, the Interuniversity
Attraction Poles (IUAP) program P6/43 of the Belgian Federal Science
Policy Office, the Prinses Beatrix Fonds, VSB Fonds, H. Kersten and M.
Kersten (Kersten Foundation), The Netherlands ALS Foundation, J. R. van
Dijk, and the Adessium Foundation. For UK sample collection support was
obtained from the Motor Neurone Disease Association of Great Britain and
Ireland, and from the Medical Research Council (UK). W. R. is supported
through the E von Behring Chair for Neuromuscular and Neurodegenerative
Disorders, and by the Interuniversity Attraction Poles (IUAP) program
P6/43 of the Belgian Federal Science Policy Office, and by the
Methusalem project of the University of Leuven. I. T. is supported by
the Agency for Innovation by Science and Technology in Flanders (IWT).
B. D., P. V. D., and S. B. are Clinical Investigators of the Fund for
Scientific Research Flanders (FWO-F). This study makes use of data
generated by the Wellcome Trust Case Control Consortium. Funding for the
project was provided by the Wellcome Trust under award 076113 and a full
list of the investigators who contributed to the generation of the data
is available from www.wtccc.org.uk.; I. Taes reports no disclosures. Dr.
Goris received a postdoctoral fellowship from the Research Foundation
Flanders (FWO-Vlaanderen) and received research support from the Belgian
Neurological Society. Dr. Lemmens and Dr. van Es report no disclosures.
Dr. van den Berg has received funding for travel and a speaker
honorarium from Baxter International Inc. Dr. Chio serves on the
editorial advisory board of Amyotrophic Lateral Sclerosis, received
research support from Ministero della Salute, Regione Piemonte,
Ministero dell'Universita e della Ricerca, Universita di Torino,
Fondazione Vialli and Mauro for ALS Research, and Federazione Italiana
Giuoco Calcio. Dr. Traynor reports no disclosures. Dr. Birve has
received research support from the Max och Edit Follins Foundation. Dr.
Andersen serves on an editorial advisory board for Amyotrophic Lateral
Sclerosis and receives research support from The Swedish Medical
Research Council, The Swedish Brain Research Foundation, Swedish Brain
Power Society, The Swedish Medical Society, and The Swedish Patient
Organization. Dr. Slowik reports no disclosures. Dr. Tomik reports no
disclosures. Dr. Brown has served on a scientific advisory board for
Biogen Idec; serves as a consultant to Acceleron Pharma and Link
Medicine; serves as board member and co-founder of AviTx; is member of
Kirac Foundation ALS Research Laboratory; has received funding for
travel from Kirac Foundation; has filed a patent on superoxide dismutase
in ALS; receives royalties from the publication of Principles of
Neurology (McGraw-Hill, 2005); serves as consultant for MPM Inc.; has
received research support from the NIH (NINDS 1RC1NS068391-01, PI
Hayward, Brown; NINDS 1RC2NS070342-01, PI R. Brown; NINDS
R01NS050557-05, PI Brown, and NINDS R01NS050557-05, PI Brown), the ALS
Therapy Alliance, the Angel Fund for ALS Research, the Pierre L.
deBourgknecht ALS Research Fund, and from the Day Neuromuscular Research
Foundation; receives Board of Directors compensation from AviTx and Link
Medicine; and receives license fee payments from AthenaGenica related to
diagnostic blood tests. Dr. Shaw has served on a scientific advisory
board for the Motor Neuron Disease Association; serves on the editorial
board of Neurodegenerative Diseases; and receives research support from
the Medical Research Council UK and from the Motor Neuron Disease
Association. Dr. Al-Chalabi serves on the editorial board of Amyotrophic
Lateral Sclerosis and as Book Editor for Complex Human Disease, A
Laboratory Manual; receives royalties from the publication of The Brain:
A Beginner's Guide (Oneworld, 2005); and receives research support from
the Medical Research Council (UK), the Wellcome Trust, the Motor Neurone
Disease Association of Great Britain and Ireland, The American ALS
Association, the ALS Therapy Alliance, and the Angel Fund. Dr. Boonen
reports no disclosures. Dr. Van Den Bosch serves on scientific advisory
boards for the Agency for Research on Amyotrophic Lateral Sclerosis
Italy (AriSLA) and receives research support from Fonds voor
Wetenschappelijk Onderzoek Vlaanderen (FWO-Vlaanderen), Association
Belge contre les Maladies neuro-Musculaires, and Association Francaise
contre les Myopathies. Dr. Dubois has served on scientific advisory
boards for Bayer Schering Pharma and Biogen Idec; has received funding
for travel from Merck Serono and Biogen Idec; and receives research
support from Merck Serono and Bayer Schering Pharma. Dr. Van Damme
reports no disclosures. Dr.; Robberecht has served on scientific
advisory boards for Acceleron Pharma, the Motor Neurone Diseae
Association, and the Thierry Latran Foundation; served as an Associate
Editor of the European Journal of Neuroscience and on the editorial
boards of the Journal of Neuropathology and Experimental Neurology and
Amyotrophic Lateral Sclerosis; has served as a consultant for NeuroNova;
receives research support from NeuroNova, Trophos, Teva Pharmaceutical
Industries Ltd., the Packard Center for ALS Research, and the Thierry
Latran Foundation; and receives funding for his laboratory from the Fund
for Scientific Research Flanders, the Institute for Innovation in
Science and Technology Flanders, the University of Leuven, the Thierry
Latran Foundation, Flanders Institute for Biotechnology, and the Packard
Center at Johns Hopkins.
NR 35
TC 11
Z9 11
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD MAY 25
PY 2010
VL 74
IS 21
BP 1687
EP 1693
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 600WA
UT WOS:000278018400006
PM 20498436
ER
PT J
AU Tomasi, D
Volkow, ND
Wang, RL
Carrillo, JH
Maloney, T
Alia-Klein, N
Woicik, PA
Telang, F
Goldstein, RZ
AF Tomasi, Dardo
Volkow, Nora D.
Wang, Ruiliang
Carrillo, Jean H.
Maloney, Thomas
Alia-Klein, Nelly
Woicik, Patricia A.
Telang, Frank
Goldstein, Rita Z.
TI Disrupted Functional Connectivity with Dopaminergic Midbrain in Cocaine
Abusers
SO PLOS ONE
LA English
DT Article
ID MEDIAL PREFRONTAL CORTEX; EMOTION-INDUCED CHANGES; WORKING-MEMORY; HUMAN
BRAIN; COGNITIVE IMPAIRMENT; ACTIVATION PATTERNS; ANTERIOR CINGULATE;
ADDICTION; TASK; ATTENTION
AB Background: Chronic cocaine use is associated with disrupted dopaminergic neurotransmission but how this disruption affects overall brain function ( other than reward/motivation) is yet to be fully investigated. Here we test the hypothesis that cocaine addicted subjects will have disrupted functional connectivity between the midbrain ( where dopamine neurons are located) and cortical and subcortical brain regions during the performance of a sustained attention task.
Methodology/Principal Findings: We measured brain activation and functional connectivity with fMRI in 20 cocaine abusers and 20 matched controls. When compared to controls, cocaine abusers had lower positive functional connectivity of midbrain with thalamus, cerebellum, and rostral cingulate, and this was associated with decreased activation in thalamus and cerebellum and enhanced deactivation in rostral cingulate.
Conclusions/Significance: These findings suggest that decreased functional connectivity of the midbrain interferes with the activation and deactivation signals associated with sustained attention in cocaine addicts.
C1 [Tomasi, Dardo; Volkow, Nora D.; Telang, Frank] NIAAA, NIH, Bethesda, MD USA.
[Volkow, Nora D.] Natl Inst Drug Abuse, NIH, Bethesda, MD USA.
[Wang, Ruiliang; Carrillo, Jean H.; Maloney, Thomas; Alia-Klein, Nelly; Woicik, Patricia A.; Goldstein, Rita Z.] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
[Carrillo, Jean H.] SUNY Stony Brook, Dept Comp Sci, Stony Brook, NY 11794 USA.
RP Tomasi, D (reprint author), NIAAA, NIH, Bethesda, MD USA.
EM tomasi@bnl.gov
RI Tomasi, Dardo/J-2127-2015
FU U.S. Department of Energy; National Institutes of Health [GCRC
5-MO1-RR-10710]; National Institute on Alcohol Abuse and Alcoholism
[2RO1AA09481, R01AA09481, Y1AA3009]; National Institute on Drug Abuse
[1R01DA023579, R21DA02062]
FX U.S. Department of Energy (Office of Biological and Environmental
Research), the National Institutes of Health (GCRC 5-MO1-RR-10710), the
National Institute on Alcohol Abuse and Alcoholism (2RO1AA09481,
R01AA09481 and Y1AA3009) and the National Institute on Drug Abuse
(1R01DA023579 and R21DA02062). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 57
TC 59
Z9 59
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 MAY 25
PY 2010
VL 5
IS 5
AR e10815
DI 10.1371/journal.pone.0010815
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 601CE
UT WOS:000278034800012
PM 20520835
ER
PT J
AU Miller, Y
Ma, BY
Nussinov, R
AF Miller, Yifat
Ma, Buyong
Nussinov, Ruth
TI Zinc ions promote Alzheimer A beta aggregation via population shift of
polymorphic states
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE conformational selection; energy landscape; metal ions; modeling amyloid
assemblies; seed polymorphism
ID MOLECULAR-DYNAMICS; BINDING SITE; AMYLOID FORMATION; METAL-BINDING;
PEPTIDE; DISEASE; COPPER; COMPLEXES; MECHANISM; PROTEIN
AB Although a key factor in Alzheimer's disease etiology is enrichment of Zn(2+) in aggregates, and there are data suggesting that zinc promotes aggregation, how Zn(2+)-A beta coordination promotes aggregation is elusive. Here we probe the structures and mechanisms through which Zn(2+) can affect amyloidosis. By covalently linking fragments (that have experiment-based coordinates) we observed that, in oligomeric Zn(2+)-A beta(42), Zn(2+) can simultaneously coordinate intra-and intermolecularly, bridging two peptides. Zinc coordination significantly decreases the solvation energy for large Zn(2+)-A beta(42) oligomers and thus enhances their aggregation tendency. Zn(2+) binding does not change the beta-sheet association around the C-terminal hydrophobic region; however, it shifts the relative population of the preexisting amyloid polymorphic ensembles. As a result, although a parallel beta-sheet arrangement is still preferred, antiparallel and other less structured assemblies are stabilized, also becoming major species. Overall, Zn(2+) coordination promotes A beta(42) aggregation leading to less uniform structures. Our replica exchange molecular dynamics simulations further reproduced an experimental observation that the increasing Zn(2+) concentration could slow down the aggregation rate, even though the aggregation rates are still much higher than in Zn(2+)-free solution.
C1 [Ma, Buyong; Nussinov, Ruth] NCI, Ctr Canc Res Nanobiol Program, Basic Sci Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel.
RP Ma, BY (reprint author), NCI, Ctr Canc Res Nanobiol Program, Basic Sci Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA.
EM mabuyong@mail.nih.gov; ruthnu@helix.nih.gov
RI Ma, Buyong/F-9491-2011
OI Ma, Buyong/0000-0002-7383-719X
FU National Cancer Institute, NIH [HHSN261200800001E]; NIH, National Cancer
Institute, Center for Cancer Research
FX We thank the Nussinov group members at the Center for Cancer Research
Nanobiology Program, National Cancer Institute-Frederick. All
simulations had been performed using the high-performance computational
facilities of the Biowulf cluster at the National Institutes of Health
(NIH). We thank Drs. E. Molteni and F. Stellato for providing the atomic
coordinates of the models obtained in their labs. This project has been
funded in whole or in part with Federal funds from the National Cancer
Institute, NIH, under Contract HHSN261200800001E. This research was
supported (in part) by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research.
NR 50
TC 145
Z9 151
U1 2
U2 47
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 MAY 25
PY 2010
VL 107
IS 21
BP 9490
EP 9495
DI 10.1073/pnas.0913114107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 601JP
UT WOS:000278054700005
PM 20448202
ER
PT J
AU Zurita, A
Zhang, YH
Pedersen, L
Darden, T
Birnbaumer, L
AF Zurita, Adolfo
Zhang, Yinghao
Pedersen, Lee
Darden, Tom
Birnbaumer, Lutz
TI Obligatory role in GTP hydrolysis for the amide carbonyl oxygen of the
Mg2+-coordinating Thr of regulatory GTPases
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE ensymes/hydrolases; protein/metal ion interaction; catalytic water;
heterotrimeric G proteins
ID ALPHA-SUBUNIT; ADENYLYL CYCLASE; G-PROTEIN; RAS; BINDING; SWITCH; FORMS;
GDP; GS; COMPONENT
AB When G-protein a subunits binds GTP and Mg2+, they transition from their inactive to their active conformation. This transition is accompanied by completion of the coordination shell of Mg2+ with electrons from six oxygens: two water molecules, the beta and. phosphoryls of GTP, a helix-alpha 1 Ser, and a switch I domain (SWI) Thr, and the repositioning of SWI and SWII domains. SWII binds and regulates effector enzymes and facilitates GTP hydrolysis by repositioning the gamma-carbonyl of a Gln. Mutating the Ser generates regulatory GTPases that cannot lock Mg2+ into its place and are locked in their inactive state with dominant negative properties. Curiously, mutating the Thr appears to reduce GTP hydrolysis. The reason for this difference is not known because it is also not known why removal of the Thr should affect the overall GTPase cycle differently than removal of the Ser. Working with recombinant Gs alpha, we report that mutating its SWI-Thr to either Ala, Glu, Gln, or Asp results not only in diminished GTPase activity but also in spontaneous activation of the SWII domain. Upon close examination of existing a subunit crystals, we noted the oxygen of the backbone carbonyl of SWI-Thr and of the gamma-carbonyl of SWII Gln to be roughly equidistant from the oxygen of the hydrolytic H2O. Our observations indicate that the Gln and Thr carbonyls play equi-hierarchical roles in the GTPase process and provide the mechanism that explains why mutating the Thr mimics mutating the Gln and not that of the Ser.
C1 [Zurita, Adolfo; Zhang, Yinghao; Pedersen, Lee; Darden, Tom; Birnbaumer, Lutz] NIEHS, Neurobiol Lab, Div Intramural Res, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Birnbaumer, L (reprint author), NIEHS, Neurobiol Lab, Div Intramural Res, NIH,Dept Hlth & Human Serv, Bldg 101,Room F180,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM birnbau1@niehs.nih.gov
RI Pedersen, Lee/E-3405-2013
OI Pedersen, Lee/0000-0003-1262-9861
FU National Institutes of Health [Z01-ES101643]
FX We thank Joseph M. Krahn from the Laboratory of Structural Biology for
fruitful discussions and his suggestion to study the effect of divalent
cation substitutions on the intrinsic GTPase activity of Gsa and its
mutants. This work was supported by the Intramural Research Program of
the National Institutes of Health (Z01-ES101643).
NR 24
TC 5
Z9 5
U1 0
U2 6
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 MAY 25
PY 2010
VL 107
IS 21
BP 9596
EP 9601
DI 10.1073/pnas.1004803107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 601JP
UT WOS:000278054700024
PM 20457940
ER
PT J
AU Soper, T
Mandin, P
Majdalani, N
Gottesman, S
Woodson, SA
AF Soper, Toby
Mandin, Pierre
Majdalani, Nadim
Gottesman, Susan
Woodson, Sarah A.
TI Positive regulation by small RNAs and the role of Hfq
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE Sigma 38; translational control; Sm-like protein; RNA-protein
interactions
ID ESCHERICHIA-COLI HFQ; SM-LIKE PROTEIN; MESSENGER-RNA; RPOS TRANSLATION;
DSRA RNA; SALMONELLA-TYPHIMURIUM; NONCODING RNAS; HOST FACTOR; BINDING;
MECHANISMS
AB Bacterial small noncoding RNAs carry out both positive and negative regulation of gene expression by pairing with mRNAs; in Escherichia coli, this regulation often requires the RNA chaperone Hfq. Three small regulatory RNAs (sRNAs), DsrA, RprA, and ArcZ, positively regulate translation of the sigma factor RpoS, each pairing with the 5' leader to open up an inhibitory hairpin. In vitro, rpoS interaction with sRNAs depends upon an (AAN)(4) Hfq-binding site upstream of the pairing region. Here we show that both Hfq and this Hfq binding site are required for RprA or ArcZ to act in vivo and to form a stable complex with rpoS mRNA in vitro; both were partially dispensable for DsrA at 37 degrees C. ArcZ sRNA is processed from 121 nt to a stable 56 nt species that contains the pairing region; only the 56 nt ArcZ makes a strong Hfq-dependent complex with rpoS. For each of these sRNAs, the stability of the sRNA center dot mRNA complexes, rather than their rate of formation, best predicted in vivo activity. These studies demonstrate that binding of Hfq to the rpoS mRNA is critical for sRNA regulation under normal conditions, but if the stability of the sRNA center dot mRNA complex is sufficiently high, the requirement for Hfq can be bypassed.
C1 [Mandin, Pierre; Majdalani, Nadim; Gottesman, Susan] NCI, Mol Biol Lab, Bethesda, MD 20892 USA.
[Soper, Toby; Woodson, Sarah A.] Johns Hopkins Univ, Program Cell Mol Dev Biol & Biophys, Baltimore, MD 21218 USA.
[Woodson, Sarah A.] Johns Hopkins Univ, TC Jenkins Dept Biophys, Baltimore, MD 21218 USA.
RP Gottesman, S (reprint author), NCI, Mol Biol Lab, Bldg 37,Room 5132, Bethesda, MD 20892 USA.
EM susang@helix.nih.gov; swoodson@jhu.edu
OI Woodson, Sarah/0000-0003-0170-1987
FU National Institute of General Medical Sciences [R01 GM46686]; National
Institutes of Health, National Cancer Institute, Center for Cancer
Research
FX We thank Subrata Panja for providing purified Hfq. We thank members of
the Woodson and Gottesman laboratories, Gisela Storz, Robert Weisberg,
and Kumaran Ramamurthi for comments on the manuscript. Research in the
Woodson lab was supported by National Institute of General Medical
Sciences (R01 GM46686). Research in the Gottesman lab was supported by
the Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research.
NR 36
TC 140
Z9 143
U1 5
U2 26
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 MAY 25
PY 2010
VL 107
IS 21
BP 9602
EP 9607
DI 10.1073/pnas.1004435107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 601JP
UT WOS:000278054700025
PM 20457943
ER
PT J
AU Simon, A
Park, H
Maddipati, R
Lobito, AA
Bulua, AC
Jackson, AJ
Chae, JJ
Ettinger, R
de Koning, HD
Cruz, AC
Kastner, DL
Komarow, H
Siegel, RM
AF Simon, Anna
Park, Heiyoung
Maddipati, Ravikanth
Lobito, Adrian A.
Bulua, Ariel C.
Jackson, Adrianna J.
Chae, Jae Jin
Ettinger, Rachel
de Koning, Heleen D.
Cruz, Anthony C.
Kastner, Daniel L.
Komarow, Hirsh
Siegel, Richard M.
TI Concerted action of wild-type and mutant TNF receptors enhances
inflammation in TNF receptor 1-associated periodic fever syndrome
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE autoinflammatory disease; genetic disease
ID SYNDROME TRAPS; AUTOINFLAMMATORY SYNDROMES; ACTIVATION; MICE; DISEASE;
ALPHA; ETANERCEPT; INHIBITION; LETHALITY; APOPTOSIS
AB TNF, acting through p55 tumor necrosis factor receptor 1 (TNFR1), contributes to the pathogenesis of many inflammatory diseases. TNFR-associated periodic syndrome (TRAPS, OMIM 142680) is an autosomal dominant autoinflammatory disorder characterized by prolonged attacks of fevers, peritonitis, and soft tissue inflammation. TRAPS is caused by missense mutations in the extracellular domain of TNFR1 that affect receptor folding and trafficking. These mutations lead to loss of normal function rather than gain of function, and thus the pathogenesis of TRAPS is an enigma. Here we show that mutant TNFR1 accumulates intracellularly in peripheral blood mononuclear cells of TRAPS patients and in multiple cell types from two independent lines of knockin mice harboring TRAPS-associated TNFR1 mutations. Mutant TNFR1 did not function as a surface receptor for TNF but rather enhanced activation of MAPKs and secretion of proinflammatory cytokines upon stimulation with LPS. Enhanced inflammation depended on autocrine TNF secretion and WT TNFR1 in mouse and human myeloid cells but not in fibroblasts. Heterozygous TNFR1-mutant mice were hypersensitive to LPS-induced septic shock, whereas homozygous TNFR1-mutant mice resembled TNFR1-deficient mice and were resistant to septic shock. Thus WT and mutant TNFR1 act in concert from distinct cellular locations to potentiate inflammation in TRAPS. These findings establish a mechanism of pathogenesis in autosomal dominant diseases where full expression of the disease phenotype depends on functional cooperation between WT and mutant proteins and also may explain partial responses of TRAPS patients to TNF blockade.
C1 [Park, Heiyoung; Maddipati, Ravikanth; Lobito, Adrian A.; Bulua, Ariel C.; Ettinger, Rachel; Cruz, Anthony C.; Siegel, Richard M.] NIAMSD, Immunoregulat Sect, Autoimmun Branch, NIH, Bethesda, MD 20892 USA.
[Simon, Anna; Jackson, Adrianna J.; Chae, Jae Jin; de Koning, Heleen D.; Kastner, Daniel L.; Komarow, Hirsh] NIAMSD, Inflammatory Biol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA.
RP Siegel, RM (reprint author), NIAMSD, Immunoregulat Sect, Autoimmun Branch, NIH, Bethesda, MD 20892 USA.
EM siegelr@mail.nih.gov
RI de Koning, Heleen/A-5374-2011; Simon, Anna/D-3757-2009;
OI Simon, Anna/0000-0002-6141-7921; Siegel, Richard/0000-0001-5953-9893
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases;
Netherlands Organization for Health Research and Development (ZonMW);
Howard Hughes Medical Institute-National Institutes of Health; National
Institutes of Health; Pfizer Inc
FX We thank Beverly Barham and John Ryan for clinical support, Mihan Lee
for technical assistance, Uli Siebenlist and Zheng-Gang Liu for reagents
and helpful advice, and Robert Colbert and Massimo Gadina for critical
reading of the manuscript. This research was supported by intramural
research funding from National Institute of Arthritis and
Musculoskeletal and Skin Diseases. A.S. is supported by a Netherlands
Organization for Health Research and Development (ZonMW) Veni grant.
A.J.J. and R.M. were supported by the Howard Hughes Medical
Institute-National Institutes of Health Scholars Program, and A.C.B. was
supported by the National Institutes of Health Clinical Research
Training Program, a public-private partnership between the Foundation
for the National Institutes of Health and Pfizer Inc.
NR 39
TC 81
Z9 81
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 MAY 25
PY 2010
VL 107
IS 21
BP 9801
EP 9806
DI 10.1073/pnas.0914118107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 601JP
UT WOS:000278054700059
PM 20457915
ER
PT J
AU Sui, YJ
Zhu, Q
Gagnon, S
Dzutsev, A
Terabe, M
Vaccari, M
Venzon, D
Klinman, D
Strober, W
Kelsall, B
Franchini, G
Belyakov, IM
Berzofsky, JA
AF Sui, Yongjun
Zhu, Qing
Gagnon, Susan
Dzutsev, Amiran
Terabe, Masaki
Vaccari, Monica
Venzon, David
Klinman, Dennis
Strober, Warren
Kelsall, Brian
Franchini, Genoveffa
Belyakov, Igor M.
Berzofsky, Jay A.
TI Innate and adaptive immune correlates of vaccine and adjuvant-induced
control of mucosal transmission of SIV in macaques
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE APOBEC3G; HIV vaccine; Toll-like receptor agonist; IL-15; Polyfunctional
T cells
ID SIMIAN IMMUNODEFICIENCY VIRUS; T-CELL RESPONSES; SIVMAC251 CHALLENGE;
RHESUS MACAQUES; DENDRITIC CELLS; APOBEC3G EXPRESSION; IL-15 PLASMID;
VIRAL LOAD; INFECTION; HIV
AB Adjuvant effects on innate as well as adaptive immunity may be critical for inducing protection against mucosal HIV and simian immunodeficiency virus (SIV) exposure. We therefore studied effects of Toll-like receptor agonists and IL-15 as mucosal adjuvants on both innate and adaptive immunity in a peptide/poxvirus HIV/SIV mucosal vaccine in macaques, and made three critical observations regarding both innate and adaptive correlates of protection: (i) adjuvant-alone without vaccine antigen impacted the intrarectal SIVmac251 challenge outcome, correlating with surprisingly long-lived APOBEC3G (A3G)-mediated innate immunity; in addition, even among animals receiving vaccine with adjuvants, viral load correlated inversely with A3G levels; (ii) a surprising threshold-like effect existed for vaccine-induced adaptive immunity control of viral load, and only antigen-specific polyfunctional CD8(+) T cells correlated with protection, not tetramer(+) T cells, demonstrating the importance of T-cell quality; (iii) synergy was observed between Toll-like receptor agonists and IL-15 for driving adaptive responses through the up-regulation of IL-15Ra, which can present IL-15 in trans, as well as for driving the innate A3G response. Thus, strategic use of molecular adjuvants can provide better mucosal protection through induction of both innate and adaptive immunity.
C1 [Sui, Yongjun; Zhu, Qing; Gagnon, Susan; Dzutsev, Amiran; Terabe, Masaki; Vaccari, Monica; Franchini, Genoveffa; Belyakov, Igor M.; Berzofsky, Jay A.] NIAID, Vaccine Branch, NIH, Bethesda, MD 20892 USA.
[Venzon, David] NIAID, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA.
[Klinman, Dennis] NIAID, Expt Immunol Lab, NCI, NIH, Bethesda, MD 20892 USA.
[Kelsall, Brian] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
RP Sui, YJ (reprint author), NIAID, Vaccine Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM suiy@mail.nih.gov; berzofsj@mail.nih.gov
FU National Institutes of Health; National Cancer Institute; Center for
Cancer Research
FX We thank J. Bacher, J. Medley, J. Dennis, and A. Cisar for veterinary
support and surgeries; M. Eckhaus and I. Cabrera for necropsies and
pathology support; R. Pal and P. Markham, and S. Orndorff for the viral
loads, CD4, and antibody assays; D. Watkins for MHC typing; Nancy Miller
for providing pathogenic SIVmac251 challenge stock; the National
Institute of Allergy and Infectious Diseases tetramer core facility for
providing the tetramers; Lisa Smith for secretarial assistance; and M.
Robert-Guroff and J. Lifson for critical reading of the manuscript and
helpful suggestions. This work was supported in part by the Intramural
Program of the National Institutes of Health, National Cancer Institute,
Center for Cancer Research, and the National Institutes of Health
Intramural AIDS Targeted Antiretroviral Program.
NR 43
TC 57
Z9 57
U1 0
U2 5
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAY 25
PY 2010
VL 107
IS 21
BP 9843
EP 9848
DI 10.1073/pnas.0911932107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 601JP
UT WOS:000278054700066
PM 20457926
ER
PT J
AU Tomasi, D
Volkow, ND
AF Tomasi, Dardo
Volkow, Nora D.
TI Functional connectivity density mapping
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE resting state functional MRI connectivity; functional connectomes;
default mode networks; scale-free networks; consciousness
ID TEST-RETEST RELIABILITY; RESTING-STATE DATA; HUMAN BRAIN; SMALL-WORLD;
ALZHEIMERS-DISEASE; WORKING-MEMORY; CORTICAL HUBS; LOW-FREQUENCY;
DEFAULT MODE; NETWORKS
AB Brain networks with energy-efficient hubs might support the high cognitive performance of humans and a better understanding of their organization is likely of relevance for studying not only brain development and plasticity but also neuropsychiatric disorders. However, the distribution of hubs in the human brain is largely unknown due to the high computational demands of comprehensive analytical methods. Here we propose a 10(3) times faster method to map the distribution of the local functional connectivity density (lFCD) in the human brain. The robustness of this method was tested in 979 subjects from a large repository of MRI time series collected in resting conditions. Consistently across research sites, a region located in the posterior cingulate/ventral precuneus (BA 23/31) was the area with the highest IFCD, which suggest that this is the most prominent functional hub in the brain. In addition, regions located in the inferior parietal cortex (BA 18) and cuneus (BA 18) had high lFCD. The variability of this pattern across subjects was <36% and within subjects was 12%. The power scaling of the lFCD was consistent across research centers, suggesting that that brain networks have a "scale-free" organization.
C1 [Tomasi, Dardo; Volkow, Nora D.] NIAAA, Bethesda, MD 20892 USA.
[Volkow, Nora D.] NIDA, Bethesda, MD 20892 USA.
RP Tomasi, D (reprint author), NIAAA, Bethesda, MD 20892 USA.
EM tomasi@bnl.gov
RI Tomasi, Dardo/J-2127-2015
FU National Institutes of Alcohol Abuse and Alcoholism [2RO1AA09481]
FX This work was accomplished with support from National Institutes of
Alcohol Abuse and Alcoholism Grant 2RO1AA09481.
NR 38
TC 188
Z9 194
U1 3
U2 27
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 MAY 25
PY 2010
VL 107
IS 21
BP 9885
EP 9890
DI 10.1073/pnas.1001414107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 601JP
UT WOS:000278054700073
PM 20457896
ER
PT J
AU Maruyama, T
Mirando, AJ
Deng, CX
Hsu, W
AF Maruyama, Takamitsu
Mirando, Anthony J.
Deng, Chu-Xia
Hsu, Wei
TI The Balance of WNT and FGF Signaling Influences Mesenchymal Stem Cell
Fate During Skeletal Development
SO SCIENCE SIGNALING
LA English
DT Article
ID GROWTH-FACTOR RECEPTORS; CRANIAL SUTURE FUSION; APERT-SYNDROME;
BONE-DEVELOPMENT; BETA-CATENIN; IN-VIVO; GENE; CRANIOSYNOSTOSIS;
EXPRESSION; MUTATION
AB Craniosynostosis, a developmental disorder resulting from premature closure of the gaps (sutures) between skull bones, can be caused by excessive intramembranous ossification, a type of bone formation that does not involve formation of a cartilage template (chondrogenesis). Here, we show that endochondral ossification, a type of bone formation that proceeds through a cartilage intermediate, caused by switching the fate of mesenchymal stem cells to chondrocytes, can also result in craniosynostosis. Simultaneous knockout of Axin2, a negative regulator of the WNT-beta-catenin pathway, and decreased activity of fibroblast growth factor (FGF) receptor 1 (FGFR1) in mice induced ectopic chondrogenesis, leading to abnormal suture morphogenesis and fusion. Genetic analyses revealed that activation of beta-catenin cooperated with FGFR1 to alter the lineage commitment of mesenchymal stem cells to differentiate into chondrocytes, from which cartilage is formed. We showed that the WNT-beta-catenin pathway directly controlled the stem cell population by regulating its renewal and proliferation, and indirectly modulated lineage specification by setting the balance of the FGF and bone morphogenetic protein pathways. This study identifies endochondral ossification as a mechanism of suture closure during development and implicates this process in craniosynostosis.
C1 [Maruyama, Takamitsu; Mirando, Anthony J.; Hsu, Wei] Univ Rochester, Med Ctr, Dept Biomed Genet, Ctr Oral Biol, Rochester, NY 14642 USA.
[Deng, Chu-Xia] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
[Hsu, Wei] Univ Rochester, Med Ctr, James Wilmot Canc Ctr, Rochester, NY 14642 USA.
RP Hsu, W (reprint author), Univ Rochester, Med Ctr, Dept Biomed Genet, Ctr Oral Biol, Rochester, NY 14642 USA.
EM wei_hsu@urmc.rochester.edu
RI deng, chuxia/N-6713-2016;
OI Hsu, Wei/0000-0001-6738-6030
FU NIDCR NIH HHS [DE15654, R01 DE015654, R01 DE015654-02, R01 DE015654-03,
R01 DE015654-04]
NR 54
TC 37
Z9 39
U1 0
U2 6
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 MAY 25
PY 2010
VL 3
IS 123
AR ra40
DI 10.1126/scisignal.2000727
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 601BC
UT WOS:000278032000002
PM 20501936
ER
PT J
AU Shi, CS
Kehrl, JH
AF Shi, Chong-Shan
Kehrl, John H.
TI TRAF6 and A20 Regulate Lysine 63-Linked Ubiquitination of Beclin-1 to
Control TLR4-Induced Autophagy
SO SCIENCE SIGNALING
LA English
DT Article
ID NF-KAPPA-B; TOLL-LIKE RECEPTORS; ADAPTIVE IMMUNITY; PHOSPHATIDYLINOSITOL
3-PHOSPHATE; INNATE; MACROPHAGES; MECHANISM; MEMBRANES; RESPONSES;
DEFENSE
AB Autophagy delivers cytoplasmic constituents to autophagolysosomes and is linked to both innate and adaptive immunity. Toll-like receptor 4 (TLR4) signaling induces autophagy and recruits Beclin-1, the mammalian homolog of yeast Atg6, to the receptor complex. We found that tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6)-mediated, Lys(63) (K63)-linked ubiquitination of Beclin-1 is critical for TLR4-triggered autophagy in macrophages. Two TRAF6-binding motifs in Beclin-1 facilitated the binding of TRAF6 and the ubiquitination of Beclin-1. Lys(117), which is strategically located in the Bcl-2 homology 3 (BH3) domain of Beclin-1, was a major site for K63-linked ubiquitination. The deubiquitinating enzyme A20 reduced the extent of K63-linked ubiquitination of Beclin-1 and limited the induction of autophagy in response to TLR signaling. Treatment of macrophages with either interferon-gamma or interleukin-1 also triggered the K63-linked ubiquitination of Beclin-1 and the formation of autophagosomes. These results indicate that the status of K63-linked ubiquitination of Beclin-1 plays a key role in regulating autophagy during inflammatory responses.
C1 [Shi, Chong-Shan; Kehrl, John H.] NIAID, Cell Mol Immunol Sect B, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Shi, CS (reprint author), NIAID, Cell Mol Immunol Sect B, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
EM cshi@niaid.nih.gov; jkehrl@niaid.nih.gov
OI Kehrl, John/0000-0002-6526-159X
FU Intramural NIH HHS
NR 35
TC 165
Z9 176
U1 2
U2 26
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 MAY 25
PY 2010
VL 3
IS 123
AR ra42
DI 10.1126/scisignal.2000751
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 601BC
UT WOS:000278032000004
PM 20501938
ER
PT J
AU Ripley, RT
Davis, JL
Kemp, CD
Steinberg, SM
Toomey, MA
Avital, I
AF Ripley, Robert T.
Davis, Jeremy L.
Kemp, Clinton D.
Steinberg, Seth M.
Toomey, Mary Ann
Avital, Itzhak
TI Prospective randomized trial evaluating mandatory second look surgery
with HIPEC and CRS vs. standard of care in patients at high risk of
developing colorectal peritoneal metastases
SO TRIALS
LA English
DT Article
ID PERIOPERATIVE INTRAPERITONEAL CHEMOTHERAPY; CYTOREDUCTIVE SURGERY;
1ST-LINE TREATMENT; FLUOROURACIL-LEUCOVORIN; COMPLETE RESECTION; CANCER;
CARCINOMATOSIS; OXALIPLATIN; MANAGEMENT; CHEMOHYPERTHERMIA
AB Background: The standard of care for colorectal peritoneal carcinomatosis is evolving from chemotherapy to cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with disease limited to the peritoneum. Peritoneal carcinomatosis from colorectal cancer treated with chemotherapy alone results in median survival of 5 to 13 months, whereas CRS with HIPEC for early peritoneal carcinomatosis from colorectal cancer resulted in median survival of 48-63 months and 5 year survival of 51%. Completeness of cytoreduction and limited disease are associated with longer survival, yet early peritoneal carcinomatosis is undetectable by conventional imaging. Exploratory laparotomy can successfully identify early disease, but this approach can only be justified in patients with high risk of peritoneal carcinomatosis. Historical data indicates that patients presenting with synchronous peritoneal carcinomatosis, ovarian metastases, perforated primary tumor, and emergency presentation with bleeding or obstructing lesions are at high risk of peritoneal carcinomatosis. Approximately 55% of these patient populations will develop peritoneal carcinomatosis. We hypothesize that performing a mandatory second look laparotomy with CRS and HIPEC for patients who are at high risk for developing peritoneal carcinomatosis from colorectal cancer will lead to improved survival as compared to patients who receive standard of care with routine surveillance.
Methods/Design: This study is a prospective randomized trial designed to answer the question whether mandatory second look surgery with CRS and HIPEC will prolong overall survival compared to the standard of care in patients who are at high risk for developing peritoneal carcinomatosis from colorectal cancer (CRC). Patients with CRC at high risk for developing peritoneal carcinomatosis who underwent curative surgery and subsequently received standard of care adjuvant chemotherapy will be evaluated. The patients who remain without evidence of disease by imaging, physical examination, and tumor markers for 12 months after the primary operation will be randomized to mandatory second look surgery or standard-of-care surveillance. At laparotomy, CRS and HIPEC will be performed with intraperitoneal oxaliplatin with concurrent systemic 5-fluorouracil and leucovorin. Up to 100 patients will be enrolled to allow for 35 evaluable patients in each arm; accrual is expected to last 5 years.
C1 [Ripley, Robert T.; Davis, Jeremy L.; Kemp, Clinton D.; Toomey, Mary Ann; Avital, Itzhak] NCI, Surg Branch, CCR, Bethesda, MD 20892 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, CCR, Bethesda, MD 20892 USA.
RP Avital, I (reprint author), NCI, Surg Branch, CCR, Bethesda, MD 20892 USA.
EM avitali@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research, Bethesda,
MD, U.S.A.
FX This study is supported by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research, Bethesda, MD,
U.S.A.
NR 36
TC 15
Z9 15
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1745-6215
J9 TRIALS
JI Trials
PD MAY 25
PY 2010
VL 11
AR 62
DI 10.1186/1745-6215-11-62
PG 8
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 621BP
UT WOS:000279548900002
PM 20500867
ER
PT J
AU Stafford, RS
Bartholomew, LK
Cushman, WC
Cutler, JA
Davis, BR
Dawson, G
Einhorn, PT
Furberg, CD
Piller, LB
Pressel, SL
Whelton, PK
AF Stafford, Randall S.
Bartholomew, L. Kay
Cushman, William C.
Cutler, Jeffrey A.
Davis, Barry R.
Dawson, Glenna
Einhorn, Paula T.
Furberg, Curt D.
Piller, Linda B.
Pressel, Sara L.
Whelton, Paul K.
CA ALLHAT Collaborative Res Grp
TI Impact of the ALLHAT/JNC7 Dissemination Project on Thiazide-Type
Diuretic Use
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article
ID CLINICAL-PRACTICE GUIDELINES; RANDOMIZED CONTROLLED-TRIAL;
LIPID-LOWERING TREATMENT; IMPLEMENTATION STRATEGIES; BLOOD-PRESSURE;
OUTCOMES; HYPERTENSION; MEDICATIONS; IMPROVEMENT; PREVENTION
AB Background: Strategies are needed to improve the translation of clinical trial results into practice We assessed the impact of the ALLHAT/JNC7 Dissemination Project's academic detailing component on thiazide-type diuretic prescribing (ALLHAT indicates Anuhypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, JNC7 indicates the Seventh Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure)
Methods: We used 2 national databases available from IMS Health a physician survey of medications reported for hypertension and a pharmacy dispensing database on antihypertensive medications At a county level, we correlated medication data with Dissemination Project intensity. Practices before the Dissemination Project in 2004 were compared with those after its completion in 2007 We also examined 2000-2008 national trends
Results: Academic detailing reached 18 524 physicians in 1698 venues via 147 investigator-educators We noted an association between ALLHAT/JNC7 academic detailing activities and increased prescribing of thiande-type diuretics Physician survey data showed that the percentage of hypertension visits where the physician recorded a thiazide-type diuretic Increased the most in counties where academic detailing activity, was the highest (an increase of 8.6%, from 37.9% to 46.5%) compared with counties where activity was moderate (an increase of 2%) or low (a decrease of 2%), or where there was none (an increase of 2%, P value for trend, < 05) Pharmacy dispensing data showed that thiazide-type diuretic prescribing increased by 8.7% in counties with Dissemination Project activities compared with 3.9% in those without activities (P< 001) Nationally, thiazide-type diuretic use did not increase between 2004 and 2008
Conclusions: The ALLHAT/JNC7 Dissemination Project was associated with a small effect on thiazide-type diuretic use consistent with its small dose and the potential of external factors to diminish its impact Academic detailing may increase physicians implementation of clinical trial results, thereby making prescribing more consistent with evidence
C1 [Bartholomew, L. Kay; Davis, Barry R.; Dawson, Glenna; Piller, Linda B.; Pressel, Sara L.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA.
[Stafford, Randall S.] Stanford Univ, Program Prevent Outcomes & Practices, Stanford Prevent Res Ctr, Stanford, CA 94305 USA.
[Cushman, William C.] Vet Affairs Med Ctr, Memphis, TN USA.
[Cutler, Jeffrey A.] NHLBI, Bethesda, MD 20892 USA.
[Furberg, Curt D.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
[Whelton, Paul K.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA.
RP Pressel, SL (reprint author), Univ Texas Hlth Sci Ctr Houston, Coordinating Ctr Clin Trials, Sch Publ Hlth, 1200 Herman Pressler St,Ste E801, Houston, TX 77030 USA.
FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-35130,
K24HL086703]; Pfizer Inc
FX Thus study vas supported by contract N01-HC-35130 from the National
Heart, Lung, and Blood Institute (NHLBI), as well as an NHLBI mentoring
award (RSS, K24HL086703) The ALLHAT Investigators acknowledge
contributions of study medications supplied by Pfizer Inc (amlodipine),
AstraZeneca (atenolol and fisinopril), and Bristol-Myers Squibb
(pravastatin) and financial support provided by Pfizer Inc The
statements, findings, conclusions, views, and opinions contained and
expressed in this article are based in part on data obtained under
license from the following IMS Health Inc information services National
Disease and Therapeutic Index (2000-2008) and Xponent (2004-2007), IMS
Health Inc Disclaimer. The statements, findings, conclusions, views, and
opinions contained and expressed herein are not necessarily those of IMS
Health Inc or any of its affiliated or subsidiary entities
NR 31
TC 26
Z9 28
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD MAY 24
PY 2010
VL 170
IS 10
BP 851
EP 858
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 599LO
UT WOS:000277914400002
PM 20498411
ER
PT J
AU Przytycka, TM
Andrews, J
AF Przytycka, Teresa M.
Andrews, Justen
TI Systems-biology dissection of eukaryotic cell growth
SO BMC BIOLOGY
LA English
DT Editorial Material
AB A recent article in BMC Biology illustrates the use of a systems-biology approach to integrate data across the transcriptome, proteome and metabolome of budding yeast in order to dissect the relationship between nutrient conditions and cell growth.
C1 [Andrews, Justen] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
[Przytycka, Teresa M.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20814 USA.
RP Andrews, J (reprint author), Indiana Univ, Dept Biol, 915 E 3rd St, Bloomington, IN 47405 USA.
EM jandrew@bio.indiana.edu
FU Intramural NIH HHS
NR 10
TC 1
Z9 1
U1 0
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1741-7007
J9 BMC BIOL
JI BMC Biol.
PD MAY 24
PY 2010
VL 8
AR 62
DI 10.1186/1741-7007-8-62
PG 5
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 601JN
UT WOS:000278054500001
PM 20529234
ER
PT J
AU Sei, Y
Li, Z
Song, J
Ren-Patterson, R
Tunbridge, EM
Iizuka, Y
Inoue, M
Alfonso, BT
Beltaifa, S
Nakai, Y
Kolachana, BS
Chen, JS
Weinberger, DR
AF Sei, Yoshitatsu
Li, Zhen
Song, Jian
Ren-Patterson, Renee
Tunbridge, Elizabeth M.
Iizuka, Yukihiko
Inoue, Masahiro
Alfonso, Berenice T.
Beltaifa, Senda
Nakai, Yoko
Kolachana, Bhaskar S.
Chen, Jingshan
Weinberger, Daniel R.
TI Epistatic and Functional Interactions of Catechol-O-Methyltransferase
(COMT) and AKT1 on Neuregulin1-ErbB Signaling in Cell Models
SO PLOS ONE
LA English
DT Article
ID PLECKSTRIN HOMOLOGY DOMAIN; PROTEIN-KINASE B/AKT; WORKING-MEMORY;
BREAST-CANCER; GENETIC-VARIATION; MESSENGER-RNA; HUMAN BRAIN;
SCHIZOPHRENIA; ASSOCIATION; RISK
AB Background: Neuregulin1 (NRG1)-ErbB signaling has been implicated in the pathogenesis of cancer and schizophrenia. We have previously reported that NRG1-stimulated migration of B lymphoblasts is PI3K-AKT1dependent and impaired in patients with schizophrenia and significantly linked to the catechol-o-methyltransferase (COMT) Val108/158Met functional polymorphism.
Methodology/Principal Findings: We have now examined AKT1 activation in NRG1-stimulated B lymphoblasts and other cell models and explored a functional relationship between COMT and AKT1. NRG1-induced AKT1 phosphorylation was significantly diminished in Val carriers compared to Met carriers in both normal subjects and in patients. Further, there was a significant epistatic interaction between a putatively functional coding SNP in AKT1 (rs1130233) and COMT Val108/158Met genotype on AKT1 phosphorylation. NRG1 induced translocation of AKT1 to the plasma membrane also was impaired in Val carriers, while PIP(3) levels were not decreased. Interestingly, the level of COMT enzyme activity was inversely correlated with the cells' ability to synthesize phosphatidylserine (PS), a factor that attracts the pleckstrin homology domain (PHD) of AKT1 to the cell membrane. Transfection of SH-SY5Y cells with a COMT Val construct increased COMT activity and significantly decreased PS levels as well as NRG1-induced AKT1 phosphorylation and migration. Administration of S-adenosylmethionine (SAM) rescued all of these deficits. These data suggest that AKT1 function is influenced by COMT enzyme activity through competition with PS synthesis for SAM, which in turn dictates AKT1-dependent cellular responses to NRG1-mediated signaling.
Conclusion/Significance: Our findings implicate genetic and functional interactions between COMT and AKT1 and may provide novel insights into pathogenesis of schizophrenia and other ErbB-associated human diseases such as cancer.
C1 [Sei, Yoshitatsu; Li, Zhen; Song, Jian; Ren-Patterson, Renee; Iizuka, Yukihiko; Alfonso, Berenice T.; Beltaifa, Senda; Nakai, Yoko; Kolachana, Bhaskar S.; Chen, Jingshan; Weinberger, Daniel R.] NIMH, Clin Brain Disorder Branch, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA.
[Tunbridge, Elizabeth M.] Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford, England.
[Inoue, Masahiro] Kurume Univ Med, Dept Infect Dis, Fukuoka, Japan.
RP Sei, Y (reprint author), NIMH, Clin Brain Disorder Branch, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA.
EM seiy@mail.nih.gov; daniel.weinberger@mail.nih.gov
OI Tunbridge, Elizabeth/0000-0002-2966-2281
FU National Institute of Mental Health, NIH; UK Medical Research Council;
University College, Oxford
FX Funding: This research was supported by the Intramural Research Program
of the National Institute of Mental Health, NIH. EMT is supported by a
project grant from the UK Medical Research Council and the Weir Junior
Research Fellowship, University College, Oxford. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 44
TC 15
Z9 15
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 MAY 24
PY 2010
VL 5
IS 5
AR e10789
DI 10.1371/journal.pone.0010789
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 601CC
UT WOS:000278034600015
PM 20520724
ER
PT J
AU Fleming, JM
Miller, TC
Quinones, M
Xiao, Z
Xu, X
Meyer, MJ
Ginsburg, E
Veenstra, TD
Vonderhaar, BK
AF Fleming, Jodie M.
Miller, Tyler C.
Quinones, Mariam
Xiao, Zhen
Xu, Xia
Meyer, Matthew J.
Ginsburg, Erika
Veenstra, Timothy D.
Vonderhaar, Barbara K.
TI The normal breast microenvironment of premenopausal women differentially
influences the behavior of breast cancer cells in vitro and in vivo
SO BMC MEDICINE
LA English
DT Article
ID MAMMARY EPITHELIAL-CELLS; AFRICAN-AMERICAN; WHITE-AMERICAN;
FUNCTIONAL-DIFFERENTIATION; TUMOR MICROENVIRONMENT; DOWN-REGULATION;
ESTROGEN; PROLIFERATION; FIBROBLASTS; GROWTH
AB Background: Breast cancer studies frequently focus on the role of the tumor microenvironment in the promotion of cancer; however, the influence of the normal breast microenvironment on cancer cells remains relatively unknown. To investigate the role of the normal breast microenvironment on breast cancer cell tumorigenicity, we examined whether extracellular matrix molecules (ECM) derived from premenopausal African-American (AA) or CaucasianAmerican (CAU) breast tissue would affect the tumorigenicity of cancer cells in vitro and in vivo. We chose these two populations because of the well documented predisposition of AA women to develop aggressive, highly metastatic breast cancer compared to CAU women.
Methods: The effects of primary breast fibroblasts on tumorigenicity were analyzed via real-time PCR arrays and mouse xenograft models. Whole breast ECM was isolated, analyzed via zymography, and its effects on breast cancer cell aggressiveness were tested in vitro via soft agar and invasion assays, and in vivo via xenograft models. Breast ECM and hormone metabolites were analyzed via mass spectrometry.
Results: Mouse mammary glands humanized with premenopausal CAU fibroblasts and injected with primary breast cancer cells developed significantly larger tumors compared to AA humanized glands. Examination of 164 ECM molecules and cytokines from CAU-derived fibroblasts demonstrated a differentially regulated set of ECM proteins and increased cytokine expression. Whole breast ECM was isolated; invasion and soft agar assays demonstrated that estrogen receptor (ER)(-), progesterone receptor (PR)/PR-cells were significantly more aggressive when in contact with AA ECM, as were ER(+)/PR(+) cells with CAU ECM. Using zymography, protease activity was comparatively upregulated in CAU ECM. In xenograft models, CAU ECM significantly increased the tumorigenicity of ER(+)/PR(+) cells and enhanced metastases. Mass spectrometry analysis of ECM proteins showed that only 1,759 of approximately 8,000 identified were in common. In the AA dataset, proteins associated with breast cancer were primarily related to tumorigenesis/neoplasia, while CAU unique proteins were involved with growth/metastasis. Using a novel mass spectrometry method, 17 biologically active hormones were measured; estradiol, estriol and 2-methoxyestrone were significantly higher in CAU breast tissue.
Conclusions: This study details normal premenopausal breast tissue composition, delineates potential mechanisms for breast cancer development, and provides data for further investigation into the role of the microenvironment in cancer disparities.
C1 [Fleming, Jodie M.; Miller, Tyler C.; Meyer, Matthew J.; Ginsburg, Erika; Vonderhaar, Barbara K.] NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Quinones, Mariam] NIAID, Bioinformat & Computat Biosci Branch, Off Sci Management & Operat, Bethesda, MD 20892 USA.
[Xiao, Zhen; Xu, Xia; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick, Frederick, MD 21701 USA.
RP Vonderhaar, BK (reprint author), NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
EM vonderhb@mail.nih.gov
NR 57
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Z9 19
U1 1
U2 7
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 MAY 21
PY 2010
VL 8
AR 27
DI 10.1186/1741-7015-8-27
PG 21
WC Medicine, General & Internal
SC General & Internal Medicine
GA 625SR
UT WOS:000279915900001
PM 20492690
ER
PT J
AU Melkevik, O
Torsheim, T
Iannotti, RJ
Wold, B
AF Melkevik, Ole
Torsheim, Torbjorn
Iannotti, Ronald J.
Wold, Bente
TI Is spending time in screen-based sedentary behaviors associated with
less physical activity: a cross national investigation
SO INTERNATIONAL JOURNAL OF BEHAVIORAL NUTRITION AND PHYSICAL ACTIVITY
LA English
DT Article
ID CHILDRENS TELEVISION; FAMILY AFFLUENCE; HEALTH BEHAVIOR; MEDIA USE;
ADOLESCENTS; YOUTH; METAANALYSIS; COUNTRIES; PATTERNS; OBESITY
AB Background: In Australia and the USA, national guidelines exist for limiting children's screen-exposure to two hours per day. This study aims to determine whether exceeding the suggested guidelines for screen-based sedentary behavior is associated with reduced levels of physical activity across different geographical regions.
Methods: Data material were taken from the 2005/2006 survey of "Health Behaviour in School-aged Children (HBSC) study; A WHO cross-National Survey". Data were collected through questionnaires from 11-, 13- and, 15-year olds. The final sample included 200,615 adolescents from 39 different countries in Europe and North America. Gender and country stratified analyses regressed time spent in leisure-time vigorous physical activity (VPA) and days of 60 minutes moderate to vigorous physical activity (MVPA) on time spent in screen-based sedentary behaviors. To simplify interpretation, the estimates from each country were pooled using a meta-analytic procedure.
Results: Exceeding 2 hrs of daily total screen-time was negatively associated with MVPA for both boys and girls, and with VPA for girls. When investigating the different types of screen-based behaviors separately, exceeding 2 hrs daily of TV viewing was associated with less MVPA for both boys and girls and less VPA for girls. Gaming was associated with less MVPA and VPA for boys, and non-gaming computer use was associated with higher levels of VPA for both genders. Stronger negative associations between physical activity and screen-based sedentary behaviors were found in countries where mean levels of physical activity were relatively high. The association between physical activity and sedentary behavior was not significantly associated with national levels of screen-based sedentary behaviors.
Conclusions: The displacement mechanism does not appear to be universal across countries. On a national level, negative associations between physical activity and screen-based sedentary behaviors are less likely to be found in countries with relatively low levels of physical activity. Consequently, national guidelines for limiting children and adolescents time in screen-based sedentary behavior may not be conducive to increasing levels of physical activity in all countries.
C1 [Melkevik, Ole; Torsheim, Torbjorn; Wold, Bente] Univ Bergen, Fac Psychol, N-5015 Bergen, Norway.
[Iannotti, Ronald J.] NICHHD, NICHD, Bethesda, MD 20892 USA.
RP Melkevik, O (reprint author), Univ Bergen, Fac Psychol, Christiesgate 13, N-5015 Bergen, Norway.
EM ole.melkevik@psyph.uib.no
OI Torsheim, Torbjorn/0000-0001-7825-4463
NR 39
TC 60
Z9 61
U1 11
U2 46
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 MAY 21
PY 2010
VL 7
AR 46
DI 10.1186/1479-5868-7-46
PG 10
WC Nutrition & Dietetics; Physiology
SC Nutrition & Dietetics; Physiology
GA 625NZ
UT WOS:000279903400001
PM 20492643
ER
PT J
AU Loukili, N
Rosenblatt-Velin, N
Rolli, J
Levrand, S
Feihl, F
Waeber, B
Pacher, P
Liaudet, L
AF Loukili, Noureddine
Rosenblatt-Velin, Nathalie
Rolli, Joelle
Levrand, Sandra
Feihl, Francois
Waeber, Bernard
Pacher, Pal
Liaudet, Lucas
TI Oxidants Positively or Negatively Regulate Nuclear Factor kappa B in a
Context-dependent Manner
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID NECROSIS-FACTOR-ALPHA; PROTEIN PHOSPHATASE 2A; HYDROGEN-PEROXIDE;
TRANSCRIPTION FACTOR; SIGNALING PATHWAY; KINASE; ACTIVATION; INHIBITION;
PEROXYNITRITE; PHOSPHORYLATION
AB Redox-based mechanisms play critical roles in the regulation of multiple cellular functions. NF-kappa B, a master regulator of inflammation, is an inducible transcription factor generally considered to be redox-sensitive, but the modes of interactions between oxidant stress and NF-kappa B are incompletely defined. Here, we show that oxidants can either amplify or suppress NF-kappa B activation in vitro by interfering both with positive and negative signals in the NF-kappa B pathway. NF-kappa B activation was evaluated in lung A549 epithelial cells stimulated with tumor necrosis factor alpha (TNF alpha), either alone or in combination with various oxidant species, including hydrogen peroxide or peroxynitrite. Exposure to oxidants after TNF alpha stimulation produced a robust and long lasting hyperactivation of NF-kappa B by preventing resynthesis of the NF-kappa B inhibitor I kappa B, thereby abrogating the major negative feedback loop of NF-kappa B. This effect was related to continuous activation of inhibitor of kappa B kinase (IKK), due to persistent IKK phosphorylation consecutive to oxidant-mediated inactivation of protein phosphatase 2A. In contrast, exposure to oxidants before TNF alpha stimulation impaired IKK phosphorylation and activation, leading to complete prevention of NF-kappa B activation. Comparable effects were obtained when interleukin-1 beta was used instead of TNF alpha as the NF-kappa B activator. This study demonstrates that the influence of oxidants on NF-kappa B is entirely context-dependent, and that the final outcome (activation versus inhibition) depends on a balanced inhibition of protein phosphatase 2A and IKK by oxidant species. Our findings provide a new conceptual framework to understand the role of oxidant stress during inflammatory processes.
C1 [Loukili, Noureddine; Rolli, Joelle; Levrand, Sandra; Liaudet, Lucas] BH 08 621 Univ Hosp, Dept Intens Care Med, Div Pathophysiol, CH-1011 Lausanne, Switzerland.
[Rosenblatt-Velin, Nathalie; Feihl, Francois; Waeber, Bernard; Liaudet, Lucas] Univ Med Ctr, Dept Med, CH-1011 Lausanne, Switzerland.
[Rosenblatt-Velin, Nathalie; Feihl, Francois; Waeber, Bernard; Liaudet, Lucas] Fac Biol & Med, CH-1011 Lausanne, Switzerland.
[Pacher, Pal] NIH, Lab Physiol Studies, NIAA, Bethesda, MD 20892 USA.
RP Liaudet, L (reprint author), BH 08 621 Univ Hosp, Dept Intens Care Med, Div Pathophysiol, CH-1011 Lausanne, Switzerland.
EM lucas.liaudet@chuv.ch
RI Pacher, Pal/B-6378-2008; Liaudet, Lucas/E-1322-2017
OI Pacher, Pal/0000-0001-7036-8108; Liaudet, Lucas/0000-0003-2670-4930
FU Swiss National Fund for Scientific Research [PP00B-68882/1,
320000-118174/1]; NIAAA, National Institutes of Health
FX This work was supported by Swiss National Fund for Scientific Research
Grants PP00B-68882/1 and 320000-118174/1 (to L. L.). This work was also
supported by the Intramural Research Program of the NIAAA, National
Institutes of Health (to P. P.).
NR 31
TC 46
Z9 47
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 MAY 21
PY 2010
VL 285
IS 21
BP 15746
EP 15752
DI 10.1074/jbc.M110.103259
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 596WJ
UT WOS:000277715900010
PM 20299457
ER
PT J
AU Barbu, EA
Zhang, J
Siraganian, RP
AF Barbu, Emilia Alina
Zhang, Juan
Siraganian, Reuben P.
TI The Limited Contribution of Fyn and Gab2 to the High Affinity IgE
Receptor Signaling in Mast Cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID FC-EPSILON-RI; ACTIVATED PROTEIN-KINASE; BASOPHILIC LEUKEMIA-CELLS;
TYROSINE KINASE; CYTOKINE PRODUCTION; T-CELLS; NUCLEAR-FACTOR; KAPPA-B;
ALLERGIC RESPONSES; SH2 DOMAIN
AB Several studies with mast cells from knock-out mice have suggested that the tyrosine kinase Fyn and its downstream substrate Gab2 may play a role in high affinity IgE receptor (Fc epsilon RI)-mediated mast cell activation. To better understand the role of these two molecules and of Syk, we transiently transfected mast cells with small interference RNA (siRNA) targeted to Fyn, Gab2, or Syk to specifically decrease their expression. The siRNA suppression of Gab2 but not Fyn reduced activation of the phosphoinositide-3-kinase (PI3K) pathway as demonstrated by the change in phosphorylation of Akt; this indicates that Gab2 but not Fyn regulates this pathway. The decreased expression of Gab2 and Fyn had minor effects on degranulation. There were also some minor changes in activation of the NFAT or NF kappa B transcription factors in cells with reduced expression of Fyn or Gab2. Decreased Gab2 but not Fyn reduced the Fc epsilon RI-induced activation of the Erk, Jnk, and p38 MAP kinases and the release of TNF-alpha. In contrast, decreased expression of Syk dramatically reduced Fc epsilon RI-induced degranulation, activation of NFAT and NF kappa B. Therefore, the reduction in expression of these proteins in mast cells indicates that Syk is the major regulator of Fc epsilon RI-mediated reactions, whereas Fyn has minor if any effects and Gab2 regulates primarily late events including MAP kinase activation and release of cytokines.
C1 [Barbu, Emilia Alina; Zhang, Juan; Siraganian, Reuben P.] NIH, Receptors & Signal Transduct Sect, Oral Infect & Immun Branch, NIDCR, Bethesda, MD 20892 USA.
RP Barbu, EA (reprint author), NIH, Receptors & Signal Transduct Sect, Oral Infect & Immun Branch, NIDCR, Bldg 49-1A16,49 Convent Dr, Bethesda, MD 20892 USA.
EM barbue@mail.nih.gov
FU National Institutes of Health, NIDCR
FX This work was supported, in whole or in part, by the Intramural Research
Program of the National Institutes of Health, NIDCR.
NR 47
TC 19
Z9 19
U1 0
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAY 21
PY 2010
VL 285
IS 21
BP 15761
EP 15768
DI 10.1074/jbc.M110.109413
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 596WJ
UT WOS:000277715900012
PM 20335178
ER
PT J
AU Pletneva, NV
Pletnev, VZ
Lukyanov, KA
Gurskaya, NG
Goryacheva, EA
Martynov, VI
Wlodawer, A
Dauter, Z
Pletnev, S
AF Pletneva, Nadya V.
Pletnev, Vladimir Z.
Lukyanov, Konstantin A.
Gurskaya, Nadya G.
Goryacheva, Ekaterina A.
Martynov, Vladimir I.
Wlodawer, Alexander
Dauter, Zbigniew
Pletnev, Sergei
TI Structural Evidence for a Dehydrated Intermediate in Green Fluorescent
Protein Chromophore Biosynthesis
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID POSTTRANSLATIONAL CHEMISTRY; CRYSTAL-STRUCTURE; GFP; MECHANISM;
VARIANTS; DECARBOXYLATION; CHROMOPROTEINS; CYCLIZATION; MATURATION;
EXCITATION
AB The acGFPL is the first-identified member of a novel, colorless and non-fluorescent group of green fluorescent protein (GFP)-like proteins. Its mutant aceGFP, with Gly replacing the invariant catalytic Glu-222, demonstrates a relatively fast maturation rate and bright green fluorescence (lambda(ex) = 480 nm, lambda(em) = 505 nm). The reverse G222E single mutation in aceGFP results in the immature, colorless variant aceGFP-G222E, which undergoes irreversible photoconversion to a green fluorescent state under UV light exposure. Here we present a high resolution crystallographic study of aceGFP and aceGFP-G222E in the immature and UV-photoconverted states. A unique and striking feature of the colorless aceGFP-G222E structure is the chromophore in the trapped intermediate state, where cyclization of the protein backbone has occurred, but Tyr-66 still stays in the native, non-oxidized form, with C(alpha) and C(beta) atoms in the sp(3) hybridization. This experimentally observed immature aceGFP-G222E structure, characterized by the non-coplanar arrangement of the imidazolone and phenolic rings, has been attributed to one of the intermediate states in the GFP chromophore biosynthesis. The UV irradiation (lambda = 250-300 nm) of aceGFP-G222E drives the chromophore maturation further to a green fluorescent state, characterized by the conventional coplanar bicyclic structure with the oxidized double Tyr-66 C(alpha) = C(beta) bond and the conjugated system of pi-electrons. Structure-based site-directed mutagenesis has revealed a critical role of the proximal Tyr-220 in the observed effects. In particular, an alternative reaction pathway via Tyr-220 rather than conventional wild type Glu-222 has been proposed for aceGFP maturation.
C1 [Pletnev, Sergei] SAIC Frederick Inc, Basic Res Program, Argonne, IL 60439 USA.
[Pletneva, Nadya V.; Pletnev, Vladimir Z.; Lukyanov, Konstantin A.; Gurskaya, Nadya G.; Goryacheva, Ekaterina A.; Martynov, Vladimir I.] Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia.
[Dauter, Zbigniew; Pletnev, Sergei] NCI, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, NIH, Argonne, IL 60439 USA.
[Wlodawer, Alexander] NCI, Prot Struct Sect, Macromol Crystallog Lab, NIH, Frederick, MD 21702 USA.
RP Pletnev, S (reprint author), SAIC Frederick Inc, Basic Res Program, 9700 S Cass Ave, Argonne, IL 60439 USA.
EM pletnevs@mail.nih.gov
RI Pletneva, Nadya/F-7839-2014; Pletnev, Vladimir/Q-6151-2016; Martynov,
Vladimir/S-3483-2016
OI Martynov, Vladimir/0000-0003-4923-6842
FU National Institutes of Health, NCI, Center for Cancer Research; National
Institutes of Health, NCI [HHSN261200800001E]; Russian Foundation for
Basic Research [09-04-00212, 08-04-01702-a]; Russian Academy of
Sciences; Russian Federation [MD-2780.2009.4]
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health, NCI, Center for Cancer Research, and
with federal funds from the National Institutes of Health, NCI, under
Contract HHSN261200800001E. This project also was supported in part by
the Russian Foundation for Basic Research (Grants 09-04-00212 and
08-04-01702-a), Molecular and Cell Biology Program Russian Academy of
Sciences, and by Grant MD-2780.2009.4 from the President of the Russian
Federation.
NR 36
TC 8
Z9 8
U1 0
U2 6
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAY 21
PY 2010
VL 285
IS 21
BP 15978
EP 15984
DI 10.1074/jbc.M109.092320
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 596WJ
UT WOS:000277715900035
PM 20220148
ER
PT J
AU Shim, M
Foley, J
Anna, C
Mishina, Y
Eling, T
AF Shim, Minsub
Foley, Julie
Anna, Colleen
Mishina, Yuji
Eling, Thomas
TI Embryonic Expression of Cyclooxygenase-2 Causes Malformations in Axial
Skeleton
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID VERTEBRAL COLUMN; BREAST-CANCER; CELLS; MICE; P53; APOPTOSIS;
PHOSPHORYLATION; CHONDROGENESIS; ACCUMULATION; SCLEROTOME
AB Cyclooxygenases (COXs) have important functions in various physiological and pathological processes. COX-2 expression is highly induced by a variety of stimuli and is observed during certain periods of embryonic development. In this report, the direct effect of COX-2 expression on embryonic development is examined in a novel COX-2 transgenic mouse model that ubiquitously expresses human COX-2 from the early stages of embryonic development. COX-2 transgenic fetuses exhibit severe skeletal malformations and die shortly after birth. Skeletal malformations are localized along the entire vertebral column and rib cage and are linked to defective formation of cartilage anlagen. The cartilage anlagen of axial skeleton fail to properly develop in transgenic embryos because of impaired precartilaginous sclerotomal condensation, which results from the reduction of cell number in the sclerotome. Despite the ubiquitous expression of COX-2, the number of apoptotic cells is highly increased in the sclerotome of transgenic embryos but not in other tissues, suggesting that it is a tissue-specific response. Therefore, the loss of sclerotomal cells due to an increased apoptosis is probably responsible for axial skeletal malformations in transgenic fetuses. In addition, the sclerotomal accumulation of p53 protein is observed in transgenic embryos, suggesting that COX-2 may induce apoptosis via the up-regulation of p53. Our results demonstrate that the aberrant COX-2 signaling during embryonic development is teratogenic and suggest a possible association of COX-2 with fetal malformations of unknown etiology.
C1 [Shim, Minsub; Anna, Colleen; Eling, Thomas] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Foley, Julie] NIEHS, Cellular & Mol Pathol Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Mishina, Yuji] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA.
RP Eling, T (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM eling@niehs.nih.gov
FU National Institutes of Health; NIEHS; Intramural Research Program
FX This work was supported, in whole or in part, by the National Institutes
of Health, NIEHS, Intramural Research Program.
NR 36
TC 13
Z9 13
U1 0
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAY 21
PY 2010
VL 285
IS 21
BP 16206
EP 16217
DI 10.1074/jbc.M109.078576
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 596WJ
UT WOS:000277715900057
PM 20236942
ER
PT J
AU Liu, WG
MacKay, JA
Dreher, MR
Chen, MN
McDaniel, JR
Simnick, AJ
Callahan, DJ
Zalutsky, MR
Chilkoti, A
AF Liu, Wenge
MacKay, J. Andrew
Dreher, Matthew R.
Chen, Mingnan
McDaniel, Jonathan R.
Simnick, Andrew J.
Callahan, Daniel J.
Zalutsky, Michael R.
Chilkoti, Ashutosh
TI Injectable intratumoral depot of thermally responsive
polypeptide-radionuclide conjugates delays tumor progression in a mouse
model
SO JOURNAL OF CONTROLLED RELEASE
LA English
DT Article
DE Local drug delivery; Thermally responsive; Elastin-like polypeptide;
Radionuclide conjugate; Tumor retention; Radiotherapy
ID ELASTIN-LIKE POLYPEPTIDE; CARTILAGINOUS TISSUE-REPAIR; TARGETED
DRUG-DELIVERY; THERMORESPONSIVE POLYMERS; PROSTATE BRACHYTHERAPY; LOCAL
HYPERTHERMIA; BREAST-CANCER; SOLID TUMORS; THERAPY; ACCUMULATION
AB This study evaluated a biodegradable drug delivery system for local cancer radiotherapy consisting of a thermally sensitive elastin-like polypeptide (ELP) conjugated to a therapeutic radionuclide. Two ELPs (49 kDa) were synthesized using genetic engineering to test the hypothesis that injectable biopolymeric depots can retain radionuclides locally and reduce the growth of tumors. A thermally sensitive polypeptide, ELP(1), was designed to spontaneously undergo a soluble-insoluble phase transition (forming viscous microparticles) between room temperature and body temperature upon intratumoral injection, while ELP(2) was designed to remain soluble upon injection and to serve as a negative control for the effect of aggregate assembly. After intratumoral administration of radionuclide conjugates of ELPs into implanted tumor xenografts in nude mice, their retention within the tumor, spatio-temporal distribution, and therapeutic effect were quantified. The residence time of the radionuclide-ELP(1) in the tumor was significantly longer than the thermally insensitive ELP2 conjugate. In addition, the thermal transition of ELP(1) significantly protected the conjugated radionuclide from dehalogenation, whereas the conjugated radionuclide on ELP(2) was quickly eliminated from the tumor and cleaved from the biopolymer. These attributes of the thermally sensitive ELP, depot improved the antitumor efficacy of iodine-131 compared to the soluble ELP(2) control. This novel injectable and biodegradable depot has the potential to control advanced-stage cancers by reducing the bulk of inoperable tumors, enabling surgical removal of de-bulked tumors, and preserving healthy tissues. Published by Elsevier B.V.
C1 [Liu, Wenge; Chen, Mingnan; McDaniel, Jonathan R.; Simnick, Andrew J.; Callahan, Daniel J.; Chilkoti, Ashutosh] Duke Univ, Dept Biomed Engn, Durham, NC 27706 USA.
[Zalutsky, Michael R.] Duke Univ, Dept Radiol, Durham, NC 27706 USA.
[MacKay, J. Andrew] Univ So Calif, Dept Pharmacol & Pharmaceut Sci, Los Angeles, CA USA.
[Dreher, Matthew R.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Liu, WG (reprint author), POB 90281, Durham, NC 27708 USA.
EM wengeliu@duke.edu
RI chen, mingnan/E-9607-2011;
OI Liu, Wenge/0000-0002-0688-1879; McDaniel, Jonathan/0000-0001-8575-3535
FU NIH [R01 CA138784, 5F32-CA-123889, RO1 EB000188]
FX This research was supported by the NIH through grant R01 CA138784 to W.
L, 5F32-CA-123889 to JAM., and RO1 EB000188 to A.C
NR 52
TC 52
Z9 52
U1 2
U2 20
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-3659
J9 J CONTROL RELEASE
JI J. Control. Release
PD MAY 21
PY 2010
VL 144
IS 1
BP 2
EP 9
DI 10.1016/j.jconrel.2010.01.032
PG 8
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 608IQ
UT WOS:000278577500002
PM 20117157
ER
PT J
AU Forbes, JG
Flaherty, DB
Ma, K
Qadota, H
Benian, GM
Wang, KA
AF Forbes, Jeffrey G.
Flaherty, Denise B.
Ma, Kan
Qadota, Hiroshi
Benian, Guy M.
Wang, Kuan
TI Extensive and Modular Intrinsically Disordered Segments in C. elegans
TTN-1 and Implications in Filament Binding, Elasticity and Oblique
Striation
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE C. elegans titin; polyproline II helix; staggered helical bundle;
circular dichroism; force sensor
ID MOLECULAR-DYNAMICS SIMULATIONS; PROTEIN-KINASE DOMAINS; POLYPROLINE-II
HELIX; CAENORHABDITIS-ELEGANS; PEVK SEGMENT; SKELETAL-MUSCLE; DILATED
CARDIOMYOPATHY; SEQUENCE COMPLEXITY; FOLD RECOGNITION; THICK FILAMENTS
AB TTN-1, a titin like protein in Caenorhabditis elegans, is encoded by a single gene and consists of multiple Ig and fibronectin 3 domains, a protein kinase domain and several regions containing tandem short repeat sequences. We have characterized sarcomere distribution, protein interaction with key myofibrillar proteins as well as the conformation malleability of representative motifs of five classes of short repeats. We report that two antibodies developed to portions of TTN-1 detect an similar to 2-MDa polypeptide on Western blots. In addition, by immunofluorescence staining, both of these antibodies localize to the I-band and may extend into the outer edge of the A-band in the obliquely striated muscle of the nematode. Six different 300-residue segments of TTN-1 were shown to variously interact with actin and/or myosin in vitro. Conformations of synthetic peptides of representative copies of each of the five classes of repeats-39-mer PEVT, 51-mer CEEEI, 42-mer AAPLE, 32-mer BLUE and 30-mer DispRep-were investigated by circular dichroism at different temperatures, ionic strengths and solvent polarities. The PEVT, CEEEI, DispRep and AAPLE peptides display a combination of a polyproline II helix and an unordered structure in aqueous solution and convert in trifluoroethanol to alpha-helix (PEVT, CEEEI, DispRep) and beta-turn (AAPLE) structures, respectively. The octads in BLUE motifs form unstable alpha-helix-like structures coils in aqueous solution and negligible heptad-based, alpha-helical coiled-coils. The alpha-helical structure, as modeled by threading and molecular dynamics simulations, tends to form helical bundles and crosses based on its 84-2-2 hydrophobic helical patterns and charge arrays on its surface. Our finding indicates that APPLE, PEVT, CEEEI and DispRep regions are all intrinsically disordered and highly reminiscent of the conformational malleability and elasticity of vertebrate titin PEVK segments. The proposed presence of long, modular and unstable alpha-helical oligomerization domains in the BLUE region of TTN-1 could bundle TTN-1 and stabilize oblique striation of the sarcomere. Published by Elsevier Ltd.
C1 [Forbes, Jeffrey G.; Ma, Kan; Wang, Kuan] NIAMSD, Muscle Prote & Nanotechnol Sect, Muscle Biol Lab, NIH, Bethesda, MD 20892 USA.
[Flaherty, Denise B.; Qadota, Hiroshi; Benian, Guy M.] Emory Univ, Dept Pathol, Atlanta, GA 30332 USA.
[Flaherty, Denise B.] Eckerd Coll, Coll Nat Sci, St Petersburg, FL 33711 USA.
RP Wang, KA (reprint author), NIAMSD, Muscle Prote & Nanotechnol Sect, Muscle Biol Lab, NIH, Bethesda, MD 20892 USA.
EM pathgb@emory.edu
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases,
NIH, DHHS; NIAMS/NIH [AR051466]
FX We thank Gustavo Gutierrez and Wanxia L. Tsai for technical assistance,
Matthew J. Houser and Jan Pohl for synthesis of peptides, Jim Sellers
for providing rabbit skeletal muscle F-actin, and Sho Ono for providing
the kettin mutant. This work was supported in part by the Intramural
Research Program of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases, NIH, DHHS (to K.W.) and NIAMS/NIH
grant AR051466 (to G.B.). This study utilized the high-performance
computational capabilities of the Biowulf PC/Linux cluster at
NIHe. NAMD was developed by the Theoretical and Computational
Biophysics Group in the Beckman Institute for Advanced Science and
Technology at the University of Illinois at Urbana-Champaign.
NR 68
TC 11
Z9 14
U1 0
U2 5
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 MAY 21
PY 2010
VL 398
IS 5
BP 672
EP 689
DI 10.1016/j.jmb.2010.03.032
PG 18
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 602YO
UT WOS:000278175200006
PM 20346955
ER
PT J
AU Chun, JH
Lu, SY
Lee, YS
Pike, VW
AF Chun, Joong-Hyun
Lu, Shuiyu
Lee, Yong-Sok
Pike, Victor W.
TI Fast and High-Yield Microreactor Syntheses of ortho-Substituted
[F-18]Fluoroarenes from Reactions of [F-18]Fluoride Ion with
Diaryliodonium Salts
SO JOURNAL OF ORGANIC CHEMISTRY
LA English
DT Article
ID NEAR-UV PHOTOINITIATOR; PAIR ELECTRON-TRANSFER; DIPHENYLIODONIUM
HALIDES; SENSITIZED PHOTOLYSIS; MICROFLUIDIC DEVICES;
NUCLEOPHILIC-ATTACK; PET; KINETICS; REACTOR; DECOMPOSITION
AB A microreactor was applied to produce ortho-substituted [F-18]fluoroarenes from the reactions of cyclotron-produced [F-18]fluoride ion (t(1/2) = 109.7 min) with diaryliodonium salts. The microreactor provided a very convenient means for running sequential reactions rapidly with small amounts of reagents under well-controlled conditions, thereby allowing reaction kinetics to be followed and Arrhenius activation energies (E-a) to be measured. Prepared symmetrical iodonium chlorides (Ar2I+Cl-) rapidly ( < 4 min) gave moderate (Ar = 2-MeOC6H4, 51%) to high (Ar = Ph or 2-MeC6H4, 85%) decay-corrected radiochemical yields (RCYs) of a single radioactive product ((ArF)-F-18). Reaction velocity with respect to Ar group was 2-MeOC6H4 < Ph < 2-MeC6H4. Activation energies were in the range 18-28 kcal/mol. Prepared unsymmetrical salts (e.g., 2-RC(6)H(4)I(+)2'-R'C6H4X-; X = Cl or OTs) also rapidly gave two products (2-(RC6H4F)-F-18 and 2-R'(C6H4F)-F-18) in generally high total RCYs (79-93%). Selectivity for product [F-18]fluoroarene was controlled by the nature of the ortho substituents. The power of ortho substituents to impart an ortho-effect was in the following order:, 2,6-di-Me > 2,4,6-tri-Me > Br > Me > Et approximate to Pr-i >> H > OMe. For (2-methyphenyl)(phenyl)iodonium chloride, the time-course of reaction product selectivity was constant and consistent with the operation of the Curtin-Hammett principle. These results will aid in the design of diaryliodonium salt precursors to F-18-labeled tracers for molecular imaging.
C1 [Chun, Joong-Hyun; Lu, Shuiyu; Pike, Victor W.] NIMH, PET Radiopharmaceut Sci Sect, Mol Imaging Branch, Bethesda, MD 20892 USA.
[Lee, Yong-Sok] NIH, Ctr Mol Modeling, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Pike, VW (reprint author), NIMH, PET Radiopharmaceut Sci Sect, Mol Imaging Branch, RM B3 C346A,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA.
EM pikev@mail.nih.gov
OI Lu, Shuiyu/0000-0003-0310-4318
FU National Institutes or Health [Z01-MH-002793]; NIH Intramural Research
Program through the Center for Information Technology
FX This research was supported by the Intramural Research Program (project
no. Z01-MH-002793) of the National Institutes or Health (National
Institute of Mental Health) and also by the NIH Intramural Research
Program through the Center for Information Technology. We are grateful
to the NIH Clinical PET Center for the production of fluorine-18.
NR 46
TC 91
Z9 91
U1 0
U2 22
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-3263
J9 J ORG CHEM
JI J. Org. Chem.
PD MAY 21
PY 2010
VL 75
IS 10
BP 3332
EP 3338
DI 10.1021/jo100361d
PG 7
WC Chemistry, Organic
SC Chemistry
GA 594IT
UT WOS:000277531200020
PM 20361793
ER
PT J
AU Li, ZY
Qi, CF
Shin, DM
Zingone, A
Newbery, HJ
Kovalchuk, AL
Abbott, CM
Morse, HC
AF Li, Zhaoyang
Qi, Chen-Feng
Shin, Dong-Mi
Zingone, Adriana
Newbery, Helen J.
Kovalchuk, Alexander L.
Abbott, Catherine M.
Morse, Herbert C., III
TI Eef1a2 Promotes Cell Growth, Inhibits Apoptosis and Activates JAK/STAT
and AKT Signaling in Mouse Plasmacytomas
SO PLOS ONE
LA English
DT Article
ID ELONGATION-FACTOR EEF1A2; MULTIPLE-MYELOMA; THERAPEUTIC TARGET; OVARIAN
CARCINOMAS; MAMMALIAN-CELLS; GENE-EXPRESSION; FACTOR 1-ALPHA; FACTOR 1A;
JAK-STAT; B-CELLS
AB Background: The canonical function of EEF1A2, normally expressed only in muscle, brain, and heart, is in translational elongation, but recent studies suggest a non-canonical function as a proto-oncogene that is overexpressed in a variety of solid tumors including breast and ovary. Transcriptional profiling of a spectrum of primary mouse B cell lineage neoplasms showed that transcripts encoding EEF1A2 were uniquely overexpressed in plasmacytomas (PCT), tumors of mature plasma cells. Cases of human multiple myeloma expressed significantly higher levels of EEF1A2 transcripts than normal bone marrow plasma cells. High-level expression was also a feature of a subset of cell lines developed from mouse PCT and from the human MM.
Methodology/Principal Findings: Heightened expression of EEF1A2 was not associated with increased copy number or coding sequence mutations. shRNA-mediated knockdown of Eef1a2 transcripts and protein was associated with growth inhibition due to delayed G1-S progression, and effects on apoptosis that were seen only under serum-starved conditions. Transcriptional profiles and western blot analyses of knockdown cells revealed impaired JAK/STAT and PI3K/AKT signaling suggesting their contributions to EEF1A2-mediated effects on PCT induction or progression.
Conclusions/Significance: EEF1A2 may play contribute to the induction or progression of some PCT and a small percentage of MM. Eef1a2 could also prove to be a useful new marker for a subset of MM and, ultimately, a possible target for therapy.
C1 [Li, Zhaoyang; Qi, Chen-Feng; Shin, Dong-Mi; Kovalchuk, Alexander L.; Morse, Herbert C., III] NIAID, Immunopathol Lab, NIH, Rockville, MD USA.
[Zingone, Adriana] USN Hosp, NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20814 USA.
[Newbery, Helen J.; Abbott, Catherine M.] Univ Edinburgh, Western Gen Hosp, Med Genet Sect, Mol Med Ctr, Edinburgh, Midlothian, Scotland.
RP Li, ZY (reprint author), NIAID, Immunopathol Lab, NIH, Rockville, MD USA.
EM hmorse@niaid.nih.gov
RI Abbott, Catherine/C-7306-2013;
OI Morse, Herbert/0000-0002-9331-3705
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases and National Cancer Institute; Wellcome Trust
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health, National Institute of Allergy and
Infectious Diseases and National Cancer Institute. Work in the lab of
CMA is supported by the Wellcome Trust. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 49
TC 15
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 MAY 21
PY 2010
VL 5
IS 5
AR e10755
DI 10.1371/journal.pone.0010755
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 600VQ
UT WOS:000278017400012
PM 20505761
ER
PT J
AU Nickerson, ML
Kostiha, BN
Brandt, W
Fredericks, W
Xu, KP
Yu, FS
Gold, B
Chodosh, J
Goldberg, M
Lu, DW
Yamada, M
Tervo, TM
Grutzmacher, R
Croasdale, C
Hoeltzenbein, M
Sutphin, J
Malkowicz, SB
Wessjohann, L
Kruth, HS
Dean, M
Weiss, JS
AF Nickerson, Michael L.
Kostiha, Brittany N.
Brandt, Wolfgang
Fredericks, William
Xu, Ke-Ping
Yu, Fu-Shin
Gold, Bert
Chodosh, James
Goldberg, Marc
Lu, Da Wen
Yamada, Masakazu
Tervo, Timo M.
Grutzmacher, Richard
Croasdale, Chris
Hoeltzenbein, Maria
Sutphin, John
Malkowicz, S. Bruce
Wessjohann, Ludger
Kruth, Howard S.
Dean, Michael
Weiss, Jayne S.
TI UBIAD1 Mutation Alters a Mitochondrial Prenyltransferase to Cause
Schnyder Corneal Dystrophy
SO PLOS ONE
LA English
DT Article
ID ESCHERICHIA-COLI; CRYSTALLINE DYSTROPHY; TOPOLOGY PREDICTION; PROTEIN
STRUCTURES; CHOLESTEROL; GENE; MEMBRANE; TRANSFERASE; METABOLISM;
BLADDER
AB Background: Mutations in a novel gene, UBIAD1, were recently found to cause the autosomal dominant eye disease Schnyder corneal dystrophy (SCD). SCD is characterized by an abnormal deposition of cholesterol and phospholipids in the cornea resulting in progressive corneal opacification and visual loss. We characterized lesions in the UBIAD1 gene in new SCD families and examined protein homology, localization, and structure.
Methodology/Principal Findings: We characterized five novel mutations in the UBIAD1 gene in ten SCD families, including a first SCD family of Native American ethnicity. Examination of protein homology revealed that SCD altered amino acids which were highly conserved across species. Cell lines were established from patients including keratocytes obtained after corneal transplant surgery and lymphoblastoid cell lines from Epstein-Barr virus immortalized peripheral blood mononuclear cells. These were used to determine the subcellular localization of mutant and wild type protein, and to examine cholesterol metabolite ratios. Immunohistochemistry using antibodies specific for UBIAD1 protein in keratocytes revealed that both wild type and N102S protein were localized sub-cellularly to mitochondria. Analysis of cholesterol metabolites in patient cell line extracts showed no significant alteration in the presence of mutant protein indicating a potentially novel function of the UBIAD1 protein in cholesterol biochemistry. Molecular modeling was used to develop a model of human UBIAD1 protein in a membrane and revealed potentially critical roles for amino acids mutated in SCD. Potential primary and secondary substrate binding sites were identified and docking simulations indicated likely substrates including prenyl and phenolic molecules.
Conclusions/Significance: Accumulating evidence from the SCD familial mutation spectrum, protein homology across species, and molecular modeling suggest that protein function is likely down-regulated by SCD mutations. Mitochondrial UBIAD1 protein appears to have a highly conserved function that, at least in humans, is involved in cholesterol metabolism in a novel manner.
C1 [Nickerson, Michael L.; Kostiha, Brittany N.; Gold, Bert; Dean, Michael] NCI, Canc & Inflammat Program, NIH, Frederick, MD 21701 USA.
[Nickerson, Michael L.] NIH, Grad Partnership Program, Bethesda, MD 20892 USA.
[Nickerson, Michael L.] George Washington Univ, Inst Biomed Sci, Program Mol Med, Washington, DC USA.
[Kostiha, Brittany N.] Hood Coll, Biomed Sci Grad Program, Frederick, MD 21701 USA.
[Brandt, Wolfgang; Wessjohann, Ludger] Leibniz Inst Plant Biochem, Dept Bioorgan Chem, Halle, Saale, Germany.
[Fredericks, William; Malkowicz, S. Bruce] Univ Penn, Dept Surg, Div Urol, Philadelphia, PA 19104 USA.
[Fredericks, William; Malkowicz, S. Bruce] Vet Affairs Med Ctr, Philadelphia, PA USA.
[Xu, Ke-Ping; Yu, Fu-Shin; Weiss, Jayne S.] Wayne State Univ, Sch Med, Kresge Eye Inst, Detroit, MI 48201 USA.
[Xu, Ke-Ping; Yu, Fu-Shin; Weiss, Jayne S.] Wayne State Univ, Sch Med, Dept Ophthalmol, Detroit, MI 48201 USA.
[Chodosh, James] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Howe Lab, Cambridge, MA 02138 USA.
[Goldberg, Marc] Inst Eye, Tulsa, OK USA.
[Lu, Da Wen] Triserv Gen Hosp, Taipei, Taiwan.
[Yamada, Masakazu] Natl Tokyo Med Ctr, Natl Inst Sensory Organs, Tokyo, Japan.
[Tervo, Timo M.] Univ Helsinki, Hosp Eye, Helsinki, Finland.
[Grutzmacher, Richard] Grutzmacher Lewis & Sierra, Sacramento, CA USA.
[Croasdale, Chris] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI USA.
[Hoeltzenbein, Maria] Max Planck Inst Mol Genet, Berlin, Germany.
[Sutphin, John] Univ Kansas, Med Ctr, Dept Ophthalmol, Prairie Village, KS USA.
[Kruth, Howard S.] NHLBI, Sect Expt Atherosclerosis, NIH, Bethesda, MD 20892 USA.
[Weiss, Jayne S.] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA.
RP Nickerson, ML (reprint author), NCI, Canc & Inflammat Program, NIH, Frederick, MD 21701 USA.
EM nickersonml@mail.nih.gov; jweiss@med.wayne.edu
RI Dean, Michael/G-8172-2012; Hoeltzenbein, Maria/B-1134-2016
OI Dean, Michael/0000-0003-2234-0631; Hoeltzenbein,
Maria/0000-0002-2451-4247
FU National Eye Institute [EY12972]; Eye Bank Association of America (JSW);
Midwest Eye Banks; National Cancer Institute, National Institutes of
Health [HHSN261200800001E]
FX This work was supported in part by a grant from the National Eye
Institute (grant EY12972 to J.S.W.) and by funding from the Eye Bank
Association of America (JSW), and the Midwest Eye Banks (J.S.W. and
K.-P.X.). This project has been funded 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 no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 34
TC 29
Z9 32
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 MAY 21
PY 2010
VL 5
IS 5
AR e10760
DI 10.1371/journal.pone.0010760
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 600VQ
UT WOS:000278017400016
PM 20505825
ER
PT J
AU Nelson, KE
Weinstock, GM
Highlander, SK
Worley, KC
Creasy, HH
Wortman, JR
Rusch, DB
Mitreva, M
Sodergren, E
Chinwalla, AT
Feldgarden, M
Gevers, D
Haas, BJ
Madupu, R
Ward, DV
Birren, B
Gibbs, RA
Methe, B
Petrosino, JF
Strausberg, RL
Sutton, GG
White, OR
Wilson, RK
Durkin, S
Gujja, S
Howarth, C
Kodira, CD
Kyrpides, N
Madupu, R
Mehta, T
Mitreva, M
Muzny, DM
Pearson, M
Pepin, K
Pati, A
Qin, X
Yandava, C
Zeng, QD
Zhang, L
Berlin, AM
Chen, L
Hepburn, TA
Johnson, J
McCorrison, J
Miller, J
Minx, P
Nusbaum, C
Russ, C
Sutton, GG
Sykes, SM
Tomlinson, CM
Young, S
Warren, WC
Badger, J
Crabtree, J
Madupu, R
Markowitz, VM
Orvis, J
Rusch, DB
Sutton, GG
Cree, A
Ferriera, S
Gillis, M
Hemphill, LD
Joshi, V
Kovar, C
Wetterstrand, KA
Abouellleil, A
Wollam, AM
Buhay, CJ
Ding, Y
Dugan, S
Fulton, LL
Fulton, RS
Holder, M
Hostetler, J
Sutton, GG
Allen-Vercoe, E
Badger, J
Clifton, SW
Earl, AM
Farmer, CN
Giglio, MG
Liolios, K
Surette, MG
Sutton, GG
Torralba, M
Xu, Q
Pohl, C
Durkin, S
Sutton, GG
Wilczek-Boney, K
Zhu, DH
AF Nelson, Karen E.
Weinstock, George M.
Highlander, Sarah K.
Worley, Kim C.
Creasy, Heather Huot
Wortman, Jennifer Russo
Rusch, Douglas B.
Mitreva, Makedonka
Sodergren, Erica
Chinwalla, Asif T.
Feldgarden, Michael
Gevers, Dirk
Haas, Brian J.
Madupu, Ramana
Ward, Doyle V.
Birren, BruceW.
Gibbs, Richard A.
Methe, Barbara
Petrosino, Joseph F.
Strausberg, Robert L.
Sutton, Granger G.
White, Owen R.
Wilson, Richard K.
Durkin, Scott
Gujja, Sharvari
Howarth, Clint
Kodira, Chinnappa D.
Kyrpides, Nikos
Madupu, Ramana
Mehta, Teena
Mitreva, Makedonka
Muzny, Donna M.
Pearson, Matthew
Pepin, Kymberlie
Pati, Amrita
Qin, Xiang
Yandava, Chandri
Zeng, Qiandong
Zhang, Lan
Berlin, Aaron M.
Chen, Lei
Hepburn, Theresa A.
Johnson, Justin
McCorrison, Jamison
Miller, Jason
Minx, Pat
Nusbaum, Chad
Russ, Carsten
Sutton, Granger G.
Sykes, Sean M.
Tomlinson, Chad M.
Young, Sarah
Warren, Wesley C.
Badger, Jonathan
Crabtree, Jonathan
Madupu, Ramana
Markowitz, Victor M.
Orvis, Joshua
Rusch, Douglas B.
Sutton, Granger G.
Cree, Andrew
Ferriera, Steve
Gillis, Marcus
Hemphill, Lisa D.
Joshi, Vandita
Kovar, Christie
Wetterstrand, Kris A.
Abouellleil, Amr
Wollam, Aye M.
Buhay, Christian J.
Ding, Yan
Dugan, Shannon
Fulton, Lucinda L.
Fulton, Robert S.
Holder, Mike
Hostetler, Jessica
Sutton, Granger G.
Allen-Vercoe, Emma
Badger, Jonathan
Clifton, Sandra W.
Earl, Ashlee M.
Farmer, Candace N.
Giglio, Michelle Gwinn
Liolios, Konstantinos
Surette, Michael G.
Sutton, Granger G.
Torralba, Manolito
Xu, Qiang
Pohl, Craig
Durkin, Scott
Sutton, Granger G.
Wilczek-Boney, Katarzyna
Zhu, Dianhui
CA Human Microbiome Jumpstart
TI A Catalog of Reference Genomes from the Human Microbiome
SO SCIENCE
LA English
DT Article
ID GUT MICROBIOME; PAN-GENOME
AB The human microbiome refers to the community of microorganisms, including prokaryotes, viruses, and microbial eukaryotes, that populate the human body. The National Institutes of Health launched an initiative that focuses on describing the diversity of microbial species that are associated with health and disease. The first phase of this initiative includes the sequencing of hundreds of microbial reference genomes, coupled to metagenomic sequencing from multiple body sites. Here we present results from an initial reference genome sequencing of 178 microbial genomes. From 547,968 predicted polypeptides that correspond to the gene complement of these strains, previously unidentified ("novel") polypeptides that had both unmasked sequence length greater than 100 amino acids and no BLASTP match to any nonreference entry in the nonredundant subset were defined. This analysis resulted in a set of 30,867 polypeptides, of which 29,987 (similar to 97%) were unique. In addition, this set of microbial genomes allows for similar to 40% of random sequences from the microbiome of the gastrointestinal tract to be associated with organisms based on the match criteria used. Insights into pan-genome analysis suggest that we are still far from saturating microbial species genetic data sets. In addition, the associated metrics and standards used by our group for quality assurance are presented.
C1 [Nelson, Karen E.; Rusch, Douglas B.; Methe, Barbara; Strausberg, Robert L.; Sutton, Granger G.; Durkin, Scott; Johnson, Justin; McCorrison, Jamison; Miller, Jason; Ferriera, Steve; Gillis, Marcus; Hostetler, Jessica; Torralba, Manolito] J Craig Venter Inst, Rockville, MD 20850 USA.
[Weinstock, George M.; Mitreva, Makedonka; Sodergren, Erica; Chinwalla, Asif T.; Wilson, Richard K.; Pepin, Kymberlie; Chen, Lei; Minx, Pat; Tomlinson, Chad M.; Warren, Wesley C.; Wollam, Aye M.; Fulton, Lucinda L.; Fulton, Robert S.; Clifton, Sandra W.; Farmer, Candace N.; Pohl, Craig] Washington Univ, Sch Med, Genome Ctr, St Louis, MO 63108 USA.
[Highlander, Sarah K.; Worley, Kim C.; Gibbs, Richard A.; Petrosino, Joseph F.; Muzny, Donna M.; Qin, Xiang; Zhang, Lan; Cree, Andrew; Hemphill, Lisa D.; Joshi, Vandita; Kovar, Christie; Buhay, Christian J.; Ding, Yan; Dugan, Shannon; Holder, Mike; Wilczek-Boney, Katarzyna; Zhu, Dianhui] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[Highlander, Sarah K.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA.
[Gibbs, Richard A.; Qin, Xiang; Zhang, Lan; Cree, Andrew; Hemphill, Lisa D.; Joshi, Vandita; Kovar, Christie; Buhay, Christian J.; Ding, Yan; Dugan, Shannon; Holder, Mike; Wilczek-Boney, Katarzyna; Zhu, Dianhui] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Creasy, Heather Huot; Wortman, Jennifer Russo; White, Owen R.; Crabtree, Jonathan; Orvis, Joshua; Giglio, Michelle Gwinn] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA.
Univ Maryland, Sch Med, Dept Genet, Dept Med, Baltimore, MD 21201 USA.
[Feldgarden, Michael; Gevers, Dirk; Haas, Brian J.; Ward, Doyle V.; Birren, BruceW.; Gujja, Sharvari; Howarth, Clint; Mehta, Teena; Mitreva, Makedonka; Pearson, Matthew; Yandava, Chandri; Zeng, Qiandong; Berlin, Aaron M.; Hepburn, Theresa A.; Nusbaum, Chad; Russ, Carsten; Sykes, Sean M.; Young, Sarah; Abouellleil, Amr; Earl, Ashlee M.] Broad Inst, Genome Sequencing & Anal Program, Cambridge, MA 02142 USA.
Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA.
[Kodira, Chinnappa D.] Genome Sequencing & Anal Program, Branford, CT 06405 USA.
[Kyrpides, Nikos; Pati, Amrita; Liolios, Konstantinos] Joint Genome Inst, Dept Energy, Walnut Creek, CA 94598 USA.
[Badger, Jonathan] J Craig Venter Inst, La Jolla, CA 92121 USA.
[Markowitz, Victor M.] Univ Calif Berkeley, Lawrence Berkeley Lab, Biol Data Management & Technol Ctr, Berkeley, CA 94720 USA.
[Wetterstrand, Kris A.] NHGRI, Bethesda, MD 20892 USA.
[Allen-Vercoe, Emma] Univ Guelph, Guelph, ON N1G 2W1, Canada.
[Surette, Michael G.] Univ Calgary, Calgary, AB T2N 4N1, Canada.
[Xu, Qiang] Osel Inc, Santa Clara, CA 95054 USA.
RP Nelson, KE (reprint author), J Craig Venter Inst, 9704 Med Ctr Dr, Rockville, MD 20850 USA.
EM kenelson@jcvi.org
RI Weinstock, George/C-6314-2013; Kyrpides, Nikos/A-6305-2014;
OI Weinstock, George/0000-0002-2997-4592; Kyrpides,
Nikos/0000-0002-6131-0462; Wortman, Jennifer/0000-0002-8713-1227; Earl,
Ashlee/0000-0001-7857-9145
FU NIH [N01 AI 30071, U54-AI084844, U54-HG003079, U54-HG004968,
U54-HG003273, U54-HG004973, HHSN272200900017C, U54-HG004969]; Crohn's
and Colitis Foundation of Canada; Fund for Scientific Research, Flanders
(Belgium); Canadian Cystic Fibrosis Foundation; Canadian Institutes of
Health Research
FX The authors gratefully acknowledge J. Warren, J. Zhang, R. G. Fowler, P.
Pham, D. Haft, J. Selengut, T. Davidsen, P. Goetz, D. Harkins, S.
Shrivastava, S. Koren, B. Walenz, L. Foster, I. Singh, Y.-h. Rogers, and
the J. Craig Venter Institute Joint Technology Center. We thank J. Xu,
S.-P. Yang, and S. Schobel for bioinformatics support; the Broad Genome
Sequencing Platform, Y. Han, V. Korchina, M. Scheel, R. Thornton and the
BCM-HGSC production team, L. Courntey, C. Fronick, O. Hall, M.
O'Laughlin, M. Cunningham, D. O'Brien, B. Theising, and the GCWU
production team for sequencing; J. Gordon, F. Dewhirst, B. Wilson, B.
White, R. Mandrell, M. Blaser, R. H. Stevens, S. Hillier, Y. Liu, Z.
Shen, D. Schauer, J. Fox, M. Allison, C. D. Sibley, D. M. Saulnier, and
G. R. Gibson for providing strains; and M. Y. Giovanni, C. L. Baker, V.
Bonazzi, C. D. Deal, S. Garges, R. W. Karp, R. W. Lunsford, J. Peterson,
M. Wright, T. T. Belachew, and C. R. Wellington for funding agency
management. We acknowledge NIH for funding this project with grants to
the J. Craig Venter Institute (grants N01 AI 30071 and U54-AI084844),
Washington University (grants U54-HG003079 and U54-HG004968), Baylor
College of Medicine (grants U54-HG003273 and U54-HG004973), and the
Broad Institute (grants HHSN272200900017C and U54-HG004969). Funding for
E. A.-V. was from the Crohn's and Colitis Foundation of Canada; D. G.
had secondary affiliation at the Laboratory of Microbiology (WE 10),
Department of Biochemistry and Microbiology, Faculty of Sciences, Ghent
University, KL Ledeganckstraat 35, 9000 Ghent, Belgium, and is indebted
to the Fund for Scientific Research, Flanders (Belgium), for a
postdoctoral fellowship and research funding for the duration of this
project; M. S. acknowledges the Canadian Cystic Fibrosis Foundation and
the Canadian Institutes of Health Research for funding of his research
for this project.
NR 15
TC 288
Z9 295
U1 4
U2 66
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 MAY 21
PY 2010
VL 328
IS 5981
BP 994
EP 999
DI 10.1126/science.1183605
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 598YW
UT WOS:000277877100032
ER
PT J
AU Hidajat, R
Kuate, S
Venzon, D
Kalyanaraman, V
Kalisz, I
Treece, J
Lian, Y
Barnett, SW
Robert-Guroff, M
AF Hidajat, Rachmat
Kuate, Seraphin
Venzon, David
Kalyanaraman, Vaniambadi
Kalisz, Irene
Treece, James
Lian, Ying
Barnett, Susan W.
Robert-Guroff, Marjorie
TI Construction and immunogenicity of replication-competent adenovirus 5
host range mutant recombinants expressing HIV-1 gp160 of SF162 and TV1
strains
SO VACCINE
LA English
DT Article
DE Replication-competent adenovirus; HIV envelope; Vaccine
ID SIMIAN-IMMUNODEFICIENCY-VIRUS; TRIPARTITE LEADER SEQUENCE; BINDING
PROTEIN COMPLEX; RHESUS MACAQUES; IMMUNE-RESPONSES; SUBTYPE-C;
NEUTRALIZING ANTIBODIES; ENVELOPE GLYCOPROTEINS; SHIV89.6P CHALLENGE;
PROTECTIVE EFFICACY
AB An HIV Env immunogen capable of eliciting broad immunity is critical for a successful vaccine. We constructed and characterized adenovirus 5 host range mutant (Ad5hr) recombinants encoding HIV(SF162) gp160 (subtype B) and HIV(TV1) gp160 (subtype C). Immunization of mice with one or both induced cellular immunity to subtype B and C peptides by ELISpot, and antibody responses with high binding titers to HIV Env of subtypes A, B, C. and E. Notably, Ad5hr-HIV(TV1) gp160 induced better cellular immunity than Ad5hr-HIV(SF162) gp160, either alone or following co-administration. Thus, the TV1 Env recombinant alone may be sufficient for eliciting immune responses against both subtype B and C envelopes. Further studies of Ad5hr-HIV(TV1) gp160 in rhesus macaques will evaluate the suitability of this insert for a future phase I clinical trial using a replication-competent Ad4 vector. Published by Elsevier Ltd.
C1 [Robert-Guroff, Marjorie] NCI, Sect Immune Biol Retroviral Infect, Vaccine Branch, NIH, Bethesda, MD 20892 USA.
[Venzon, David] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA.
[Kalyanaraman, Vaniambadi; Kalisz, Irene; Treece, James] Adv BioSci Labs Inc, Kensington, MD 20895 USA.
[Lian, Ying] Chiron Corp, Emeryville, CA 94608 USA.
[Barnett, Susan W.] Novartis Vaccines & Diagnost, Cambridge, MA 02139 USA.
RP Robert-Guroff, M (reprint author), NCI, Sect Immune Biol Retroviral Infect, Vaccine Branch, NIH, Bldg 41,Rm D804, Bethesda, MD 20892 USA.
EM guroffm@mail.nih.gov
FU National Institutes of Health, National Cancer Institute
FX The following reagents were obtained through the AIDS Research and
Reference Reagent Program, Division of AIDS, NIAID, NIH: HIV-1 consensus
subtype B and subtype C Env (15-mer) peptides, complete sets. This work
was supported by the Intramural Research Program of the National
Institutes of Health, National Cancer Institute.
NR 48
TC 4
Z9 5
U1 0
U2 1
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 MAY 21
PY 2010
VL 28
IS 23
BP 3963
EP 3971
DI 10.1016/j.vaccine.2010.03.046
PG 9
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 613NI
UT WOS:000278985600014
PM 20382241
ER
PT J
AU Tan, TG
Mui, E
Cong, H
Witola, WH
Montpetit, A
Muench, SP
Sidney, J
Alexander, J
Sette, A
Grigg, ME
Maewal, A
McLeod, R
AF Tan, Tze Guan
Mui, Ernest
Cong, Hua
Witola, William H.
Montpetit, Alexandre
Muench, Stephen P.
Sidney, John
Alexander, Jeff
Sette, Alessandro
Grigg, Michael E.
Maewal, Ajesh
McLeod, Rima
TI Identification of T-gondii epitopes, adjuvants, and host genetic factors
that influence protection of mice and humans
SO VACCINE
LA English
DT Article
DE Toxoplasma gondii; Vaccine; HLA Class 1 bound peptides
ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-I SUPERTYPES; T-CELL EPITOPES;
CONGENITAL TOXOPLASMOSIS; ENDOPLASMIC-RETICULUM; TRANSGENIC MICE; CTL
EPITOPES; INFECTION; PEPTIDE; MOLECULES
AB Toxoplasma gondii is an intracellular parasite that causes severe neurologic and ocular disease in immune-compromised and congenitally infected individuals. There is no vaccine protective against human toxoplasmosis. Herein, immunization of L(d) mice with HF10 (HPGSVNEFDF) with palmitic acid moieties or a monophosphoryl lipid A derivative elicited potent IFN-gamma production from L(d)-restricted CD8(+) T cells in vitro and protected mice. CD8(+) T cell peptide epitopes from T. gondii dense granule proteins GRA 3, 6, 7, and Sag 1, immunogenic in humans for HLA-A02(+), HLA-A03(+), and HLA-B07(+) cells were identified. Since peptide repertoire presented by MHC class I molecules to CD8(+) T cells is shaped by endoplasmic reticulum-associated aminopeptidase (ERAAP), polymorphisms in the human ERAAP gene ERAP1 were studied and associate with susceptibility to human congenital toxoplasmosis (p <0.05). These results have important implications for vaccine development. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Tan, Tze Guan; Mui, Ernest; Cong, Hua; Witola, William H.; McLeod, Rima] Univ Chicago, Dept Surg, Comm Immunol, Inst Genom & Syst Biol, Chicago, IL 60637 USA.
[Tan, Tze Guan; Mui, Ernest; Cong, Hua; Witola, William H.; McLeod, Rima] Univ Chicago, Comm Mol Med, Inst Genom & Syst Biol, Chicago, IL 60637 USA.
[Tan, Tze Guan; Mui, Ernest; Cong, Hua; Witola, William H.; McLeod, Rima] Univ Chicago, Comm Genet, Inst Genom & Syst Biol, Chicago, IL 60637 USA.
[Tan, Tze Guan; Mui, Ernest; Cong, Hua; Witola, William H.; McLeod, Rima] Univ Chicago, Dept Pediat Infect Disease, Comm Immunol, Inst Genom & Syst Biol, Chicago, IL 60637 USA.
[Tan, Tze Guan; Mui, Ernest; Cong, Hua; Witola, William H.; McLeod, Rima] Univ Chicago, Comm Mol Med, Inst Genom & Syst Biol, Chicago, IL 60637 USA.
[Tan, Tze Guan; Mui, Ernest; Cong, Hua; Witola, William H.; McLeod, Rima] Univ Chicago, Comm Genet, Inst Genom & Syst Biol, Chicago, IL 60637 USA.
[Cong, Hua] Shandong Univ, Dept Parasitol, Sch Med, Jinan 250012, Shandong, Peoples R China.
[Montpetit, Alexandre] Genome Quebec, Ctr Innovat, Montreal, PQ H3A 1A4, Canada.
[Muench, Stephen P.] Univ Leeds, Inst Membrane & Syst Biol, Fac Biol Sci, Leeds LS2 9JT, W Yorkshire, England.
[Sidney, John; Sette, Alessandro] La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA 92037 USA.
[Alexander, Jeff] Pharmexa Epimmune, San Diego, CA 92121 USA.
[Grigg, Michael E.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Maewal, Ajesh] Synthet Biomol, San Diego, CA 92121 USA.
RP McLeod, R (reprint author), Univ Chicago, Dept Surg, Comm Immunol, Inst Genom & Syst Biol, 5841 S Maryland Ave,AMB S206,MC 2114, Chicago, IL 60637 USA.
EM rmcleod@midway.uchicago.edu
OI Muench, Stephen/0000-0001-6869-4414
FU Fin Charity Trust; Dominique Cornwell and Peter Mann Family Foundation;
Intervet/Schering Plough; Toxoplasmosis Research Institute; DMID-NIAID
[U01 A177887]; NIH, NIAID; The Research to Prevent Blindness Foundation
FX We thank C. Oseroff for helpful suggestions, P. Terasaki for HIA-typing,
J. Boothroyd and S. Kim for the luciferase expressing parasite, N.
Blanchard and N. Shastri for sharing pre-publication data and other
suggestions, S. Reed for adjuvants, T. Gajewski and M. Alegre for their
helpful comments, and families and collaborating physicians/scientists
in the NCCCTS who made this work possible. We gratefully acknowledge
support of this work by gifts from the Fin Charity Trust, R. Blackfoot,
R. Thewind, A. Akfortseven, S. Gemma, S. Jackson, A.K. Bump, the Rooney
Aldens, the Dominique Cornwell and Peter Mann Family Foundation, the
Morel, Rosenstein, Kapnick, Taub, Latsko, and Kiewit families,
Intervet/Schering Plough, and Toxoplasmosis Research Institute. This
work also was supported by DMID-NIAID U01 A177887 (RM) and the
Intramural Research Program (NIH, NIAID [MG]) and The Research to
Prevent Blindness Foundation.
NR 52
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U1 2
U2 11
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 MAY 21
PY 2010
VL 28
IS 23
BP 3977
EP 3989
DI 10.1016/j.vaccine.2010.03.028
PG 13
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 613NI
UT WOS:000278985600016
PM 20347630
ER
PT J
AU Fewkes, NM
Krauss, AC
Guimond, M
Meadors, JL
Dobre, S
Mackall, CL
AF Fewkes, Natasha M.
Krauss, Aviva C.
Guimond, Martin
Meadors, Joanna L.
Dobre, Stefania
Mackall, Crystal L.
TI Pharmacologic modulation of niche accessibility via tyrosine kinase
inhibition enhances marrow and thymic engraftment after hematopoietic
stem cell transplantation
SO BLOOD
LA English
DT Article
ID MIXED CHIMERISM; PROGENITOR CELLS; GROWTH-FACTOR; C-KIT; TOLERANCE;
IRRADIATION; RECEPTORS; EFFICACY; DISEASES; SU11248
AB Essential survival signals within hematopoietic stem cell (HSC) and thymic niches are mediated by receptor tyrosine kinases, which can be reversibly inhibited using clinically available drugs. We studied whether sunitinib, a multityrosine kinase inhibitor that inhibits KIT, enhances engraftment after bone marrow transplantation (BMT) in mice. Sunitinib diminished hematopoietic progenitor cell numbers, and sunitinib enhanced marrow, peripheral myeloid, and lymphoid engraftment after BMT in Rag1(-/-) mice. Sunitinib augmented HSC engraftment because recipients displayed increased myeloid and lymphoid engraftment and because sunitinib-treated recipients of purified HSCs showed enhanced engraftment of secondary hosts. However, sunitinib preferentially augmented T-cell engraftment with lesser effects on myeloid and HSC engraftment. Consistent with this, sunitinib preferentially depleted the early thymic progenitor subset in the thymus. Sunitinib did not increase engraftment in mice with deficient KIT signaling, and the pattern of more potent effects on T cell compared with HSC engraftment observed in sunitinib-treated hosts was also observed after BMT into KIT(W/Wv) mice. These results implicate KIT as a critical modulator of thymic niches. We conclude that transient, pharmacologic inhibition of KIT enhances accessibility of marrow and thymic niches, and provides a novel, noncytotoxic approach to accomplish engraftment after stem cell transplantation. (Blood. 2010; 115(20): 4120-4129)
C1 [Fewkes, Natasha M.; Krauss, Aviva C.; Guimond, Martin; Meadors, Joanna L.; Dobre, Stefania; Mackall, Crystal L.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Fewkes, Natasha M.] Howard Hughes Med Inst, NIH, Res Scholars Program, Bethesda, MD 20817 USA.
[Krauss, Aviva C.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
RP Fewkes, NM (reprint author), 10 CRC 1W 3750,10 Ctr Dr,MSC 1104, Bethesda, MD 20892 USA.
EM fewkesnm@mail.nih.gov
FU Experimental Transplantation and Immunology Branch Flow Cytometry Core;
National Institutes of Health
FX The authors thank Dr Dan Fowler for his careful review of the
manuscript, the Experimental Transplantation and Immunology Branch Flow
Cytometry Core for support of our studies, and Alan Chiet for expert
compounding of sunitinib administered in these experiments.; This work
was supported by the National Institutes of Health (Intramural Research
Program).
NR 33
TC 11
Z9 12
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 MAY 20
PY 2010
VL 115
IS 20
BP 4120
EP 4129
DI 10.1182/blood-2009-10-248898
PG 10
WC Hematology
SC Hematology
GA 599OS
UT WOS:000277923600017
PM 20231424
ER
PT J
AU Smith, MA
Seibel, NL
Altekruse, SF
Ries, LAG
Melbert, DL
O'Leary, M
Smith, FO
Reaman, GH
AF Smith, Malcolm A.
Seibel, Nita L.
Altekruse, Sean F.
Ries, Lynn A. G.
Melbert, Danielle L.
O'Leary, Maura
Smith, Franklin O.
Reaman, Gregory H.
TI Outcomes for Children and Adolescents With Cancer: Challenges for the
Twenty-First Century
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID ACUTE-LYMPHOBLASTIC-LEUKEMIA; NATIONAL WILMS-TUMOR;
PEDIATRIC-ONCOLOGY-GROUP; NON-HODGKINS-LYMPHOMA; PRIMITIVE
NEUROECTODERMAL TUMOR; HIGH-RISK NEUROBLASTOMA; HIGH-DOSE METHOTREXATE;
CHILDHOOD-CANCER; UNITED-STATES; FRACTIONATED CYCLOPHOSPHAMIDE
AB Purpose
This report provides an overview of current childhood cancer statistics to facilitate analysis of the impact of past research discoveries on outcome and provide essential information for prioritizing future research directions.
Methods
Incidence and survival data for childhood cancers came from the Surveillance, Epidemiology, and End Results 9 (SEER 9) registries, and mortality data were based on deaths in the United States that were reported by states to the Centers for Disease Control and Prevention by underlying cause.
Results
Childhood cancer incidence rates increased significantly from 1975 through 2006, with increasing rates for acute lymphoblastic leukemia being most notable. Childhood cancer mortality rates declined by more than 50% between 1975 and 2006. For leukemias and lymphomas, significantly decreasing mortality rates were observed throughout the 32-year period, though the rate of decline slowed somewhat after 1998. For remaining childhood cancers, significantly decreasing mortality rates were observed from 1975 to 1996, with stable rates from 1996 through 2006. Increased survival rates were observed for all categories of childhood cancers studied, with the extent and temporal pace of the increases varying by diagnosis.
Conclusion
When 1975 age-specific death rates for children are used as a baseline, approximately 38,000 childhood malignant cancer deaths were averted in the United States from 1975 through 2006 as a result of more effective treatments identified and applied during this period. Continued success in reducing childhood cancer mortality will require new treatment paradigms building on an increased understanding of the molecular processes that promote growth and survival of specific childhood cancers.
C1 [Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
Childrens Oncol Grp, Bethesda, MD USA.
Informat Management Serv Inc, Silver Spring, MD USA.
Cincinnati Childrens Hosp Med Ctr, Div Hematol Oncol, Cincinnati, OH USA.
RP Smith, MA (reprint author), NCI, Canc Therapy Evaluat Program, Div Canc Control & Populat Sci, Room 7025,Execut Plaza N,6130 Execut Blvd, Bethesda, MD 20892 USA.
EM Malcolm.Smith@NIH.GOV
FU National Cancer Institute (NCI) [U10 CA098543]
FX Supported in part by Grant No. U10 CA098543 from the National Cancer
Institute (NCI), and by NCI contracts with SEER registries.
NR 62
TC 313
Z9 328
U1 3
U2 21
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 MAY 20
PY 2010
VL 28
IS 15
BP 2625
EP 2634
DI 10.1200/JCO.2009.27.0421
PG 10
WC Oncology
SC Oncology
GA 598JO
UT WOS:000277832400020
PM 20404250
ER
PT J
AU Andre, T
Shi, Q
Yothers, GA
Bot, BM
Haller, DG
Van Cutsem, E
Cassidy, J
Benedetti, J
O'Connell, M
Sargent, DJ
AF Andre, T.
Shi, Q.
Yothers, G. A.
Bot, B. M.
Haller, D. G.
Van Cutsem, E.
Cassidy, J.
Benedetti, J.
O'Connell, M.
Sargent, D. J.
TI Outcomes following adjuvant treatment (AT) for colon cancer (CC)
1978-1995 versus 1996-2007: Impact on recurrence rate, from recurrence
to death (TRD), and overall survival (OS)-Findings from the ACCENT
dataset
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Hop La Pitie Salpetriere, Paris, France.
Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA.
Ctr Biostat, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA.
Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA.
Mayo Clin Rochester, Rochester, MN USA.
Univ Penn, Dept Hematol Oncol, Philadelphia, PA 19104 USA.
Univ Hosp Gasthuisberg, Dept Digest Oncol, B-3000 Louvain, Belgium.
Beatson West Scotland Canc Ctr, Glasgow, Lanark, Scotland.
SWOG Stat Ctr, Seattle, WA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2010
VL 28
IS 15
SU S
MA 3616
PG 1
WC Oncology
SC Oncology
GA V30YT
UT WOS:000208852003428
ER
PT J
AU Arnaldez, FI
Yeung, CL
Grohar, PJ
Helman, LJ
AF Arnaldez, F. I.
Yeung, C. L.
Grohar, P. J.
Helman, L. J.
TI Use of loss of function RNA interference screen to evaluate TNK-2 as a
factor involved in rhabdomyosarcoma cell growth.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2010
VL 28
IS 15
SU S
MA 9525
PG 1
WC Oncology
SC Oncology
GA V30YT
UT WOS:000208852005454
ER
PT J
AU Basch, EM
Reeve, BB
Cleeland, CS
Sloan, JA
Mendoza, TR
Abemethy, AP
Bruner, D
Minasian, LM
Burke, LB
Schrag, D
AF Basch, E. M.
Reeve, B. B.
Cleeland, C. S.
Sloan, J. A.
Mendoza, T. R.
Abemethy, A. P.
Bruner, D.
Minasian, L. M.
Burke, L. B.
Schrag, D.
CA PRO-CTCAE Investigators
TI Development of the patient-reported version of the common terminology
criteria for adverse events (PRO-CTCAE)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
NCI, Bethesda, MD 20892 USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Mayo Clin Rochester, Rochester, MN USA.
Duke Univ, Med Ctr, Durham, NC USA.
Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
US FDA, Silver Spring, MD USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2010
VL 28
IS 15
SU S
MA e19605
PG 1
WC Oncology
SC Oncology
GA V30YT
UT WOS:000208852001668
ER
PT J
AU Berkowitz, JL
Janik, JE
Stewart, DM
Floravanti, S
Jaffe, ES
Fleisher, TA
Urquhart, N
Wharfs, GH
Waldmann, TA
Morris, JC
AF Berkowitz, J. L.
Janik, J. E.
Stewart, D. M.
Floravanti, S.
Jaffe, E. S.
Fleisher, T. A.
Urquhart, N.
Wharfs, G. H.
Waldmann, T. A.
Morris, J. C.
TI Phase II trial of daclizumab in human T-cell lymphotropic virus type-1
(HTLV-1)-associated adult T-cell leukemia/lymphoma (ATL)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 NCI, Metab Branch, Bethesda, MD 20892 USA.
NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
NIH, Dept Clin Pathol, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA.
Univ W Indies, Dept Pathol, Kingston 7, Jamaica.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2010
VL 28
IS 15
SU S
MA 8043
PG 1
WC Oncology
SC Oncology
GA V30YT
UT WOS:000208852005063
ER
PT J
AU Blumenthal, GM
Ballas, MS
Bernstein, W
Shamloo, BK
Root, H
Helsabeck, C
Chun, G
Figg, WD
Giaccone, G
Dennis, PA
AF Blumenthal, G. M.
Ballas, M. S.
Bernstein, W.
Shamloo, B. K.
Root, H.
Helsabeck, C.
Chun, G.
Figg, W. D.
Giaccone, G.
Dennis, P. A.
CA Thoracic Oncology Grp
TI A phase I/II trial of pemetrexed and sirolimus in advanced NSCLC
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 NCI, Bethesda, MD 20892 USA.
NYU, Ctr Canc, New York, NY USA.
NCI, Mol Pharmacol Sect, Bethesda, MD 20892 USA.
RI Figg Sr, William/M-2411-2016
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2010
VL 28
IS 15
SU S
MA 7600
PG 1
WC Oncology
SC Oncology
GA V30YT
UT WOS:000208852004733
ER
PT J
AU Busaidy, N
Kurzrock, R
LoRusso, P
Owens, AD
Chen, HX
Doyle, L
Zhang, J
Lawhorn, K
Chandhasin, C
Naing, A
AF Busaidy, N.
Kurzrock, R.
LoRusso, P.
Owens, A. D.
Chen, H. X.
Doyle, L.
Zhang, J.
Lawhorn, K.
Chandhasin, C.
Naing, A.
TI Hyperglycemia, hypertriglyceridemia, and hypercholesterolemia in a phase
I trial of the combination of an mTOR inhibitor and IGF-1 receptor
inhibitor.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
NCI, Canc Therapy Evaluat Program, Rockville, MD USA.
NCI, Canc Therapy Evaluat Program, NIH, Rockville, MD USA.
Karmanos Canc Ctr, Detroit, MI USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2010
VL 28
IS 15
SU S
MA 2597
PG 1
WC Oncology
SC Oncology
GA V30YT
UT WOS:000208852003188
ER
PT J
AU Cabanillas, ME
Kurzrock, R
Sherman, SI
Tsimberidou, AM
Waguespack, S
Naing, A
Busaidy, N
Gagel, R
Wright, JJ
Hong, DS
AF Cabanillas, M. E.
Kurzrock, R.
Sherman, S. I.
Tsimberidou, A. M.
Waguespack, S.
Naing, A.
Busaidy, N.
Gagel, R.
Wright, J. J.
Hong, D. S.
TI Phase I trial of combination sorafenib and tipifarnib: The experience in
advanced differentiated thyroid cancer (DTC) and medullary thyroid
cancer (MTC)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2010
VL 28
IS 15
SU S
MA 5586
PG 1
WC Oncology
SC Oncology
GA V30YT
UT WOS:000208852004263
ER
PT J
AU Campbell, A
Reckamp, KL
Camidge, DR
Giaccone, G
Gadgeel, SM
Khuri, FR
Engelman, JA
Denis, LJ
O'Connell, JP
Janne, PA
AF Campbell, A.
Reckamp, K. L.
Camidge, D. R.
Giaccone, G.
Gadgeel, S. M.
Khuri, F. R.
Engelman, J. A.
Denis, L. J.
O'Connell, J. P.
Janne, P. A.
TI PF-00299804 (PF299) patient (pt)-reported outcomes (PROs) and efficacy
in adenocarcinoma (adeno) and nonadeno non-small cell lung cancer
(NSCLC): A phase (P) II trial in advanced NSCLC after failure of
chemotherapy (CT) and erlotinib (E)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Pfizer Inc, New London, CT USA.
City Hope Natl Med Ctr, Duarte, CA USA.
Univ Colorado Denver, Aurora, CO USA.
NCI, Bethesda, MD 20892 USA.
Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA.
Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 20
Z9 20
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2010
VL 28
IS 15
SU S
MA 7596
PG 1
WC Oncology
SC Oncology
GA V30YT
UT WOS:000208852004729
ER
PT J
AU Cheng, SK
Dietrich, MS
Finnigan, S
Dilts, DM
AF Cheng, S. K.
Dietrich, M. S.
Finnigan, S.
Dilts, D. M.
TI Early indicators of accrual success: Time-to-first-patient and accrual
performance at an anticipated enrollment milestone-A study of
NCI-CTEP-sponsored clinical trials
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
Vanderbilt Univ, Med Ctr, Nashville, TN USA.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2010
VL 28
IS 15
SU S
MA 6001
PG 1
WC Oncology
SC Oncology
GA V30YT
UT WOS:000208852004280
ER
PT J
AU Chow, SL
Lin, Y
LoConte, NK
Royds, RB
Nekrassova, TG
Ivy, SP
Mauer, J
Wilding, G
Stoller, R
Egorin, MJ
AF Chow, S. L.
Lin, Y.
LoConte, N. K.
Royds, R. B.
Nekrassova, T. G.
Ivy, S. P.
Mauer, J.
Wilding, G.
Stoller, R.
Egorin, M. J.
TI Enrollment of and toxicity in patients 70 years and older on
CTEP/NCI-sponsored, single-agent phase I studies from 1980 to 2005.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA.
Theradex, Princeton, NJ USA.
NCI, Rockville, MD USA.
NCI, CTEP, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2010
VL 28
IS 15
SU S
MA 9119
PG 1
WC Oncology
SC Oncology
GA V30YT
UT WOS:000208852005384
ER
PT J
AU Cohn, DE
Nuovo, G
Coffey, MC
O'Malley, D
Villalona-Calero, MA
Grever, MR
Deam, D
Zwiebel, JA
Phelps, MA
AF Cohn, D. E.
Nuovo, G.
Coffey, M. C.
O'Malley, D.
Villalona-Calero, M. A.
Grever, M. R.
Deam, D.
Zwiebel, J. A.
Phelps, M. A.
TI Phase I/II trial of reovirus serotype 3-Dearing strain in patients with
recurrent ovarian cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Ohio State Univ, Div Gynecol Oncol, Columbus, OH 43210 USA.
Ohio State Univ, Med Ctr, Columbus, OH 43210 USA.
Oncolyt Biotech Inc, Calgary, AB, Canada.
NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
RI OMalley, David/E-3789-2011
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2010
VL 28
IS 15
SU S
MA TPS253
PG 1
WC Oncology
SC Oncology
GA V30YT
UT WOS:000208852002253
ER
PT J
AU Correa, R
Mackay, H
Hirte, HW
Morgan, R
Welch, S
Fleming, GF
Wang, L
Blattier, C
Ivy, SP
Oza, AM
AF Correa, R.
Mackay, H.
Hirte, H. W.
Morgan, R.
Welch, S.
Fleming, G. F.
Wang, L.
Blattier, C.
Ivy, S. P.
Oza, A. M.
TI A phase II study of sunitinib in recurrent or metastatic endometrial
carcinoma: A trial of the Princess Margaret Hospital, The University of
Chicago, and California Cancer Phase II Consortia
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
Univ Hlth Network, Princess Margaret Hosp, Toronto, ON, Canada.
Juravinski Canc Ctr, Hamilton, ON, Canada.
City Hope Natl Med Ctr, Duarte, CA USA.
London Reg Canc Ctr, London, England.
Univ Chicago, Med Ctr, Chicago, IL 60637 USA.
NCI, Rockville, MD USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2010
VL 28
IS 15
SU S
MA 5038
PG 1
WC Oncology
SC Oncology
GA V30YT
UT WOS:000208852004094
ER
PT J
AU Crew, KD
Brown, P
Greenlee, H
Bevers, TB
Arun, B
Hudis, C
McArthur, HL
Vornik, L
Cornelison, TL
Hershman, DL
AF Crew, K. D.
Brown, P.
Greenlee, H.
Bevers, T. B.
Arun, B.
Hudis, C.
McArthur, H. L.
Vornik, L.
Cornelison, T. L.
Hershman, D. L.
CA Phase I II Chemoprevention Trials
TI Phase IB randomized, double-blinded, placebo-controlled, dose-escalation
study of polyphenon E in women with a history of hormone
receptor-negative breast cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Columbia Univ, New York, NY USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY USA.
Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2010
VL 28
IS 15
SU S
MA TPS142
PG 1
WC Oncology
SC Oncology
GA V30YT
UT WOS:000208852002145
ER
PT J
AU Curiel, DT
Preuss, M
Wang, M
Kimball, KJ
Barnes, MN
Wan, W
Siegal, G
Harris, R
Aurigemma, R
Alvarez, RD
AF Curiel, D. T.
Preuss, M.
Wang, M.
Kimball, K. J.
Barnes, M. N.
Wan, W.
Siegal, G.
Harris, R.
Aurigemma, R.
Alvarez, R. D.
TI A phase I study of the infectivity enhanced CRAd Ad5-Delta 24RGD for
recurrent gynecologic cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Univ Alabama Birmingham, Birmingham, AL USA.
SAIC Frederick, Frederick, MD USA.
NIAID, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2010
VL 28
IS 15
SU S
MA 5107
PG 1
WC Oncology
SC Oncology
GA V30YT
UT WOS:000208852004162
ER
PT J
AU Dan, TD
Ly, D
Hewitt, SM
Soule, BP
Nowacki, AS
Gillespie, J
Danforth, DN
Mitchell, JB
Camphausen, KA
Simone, NL
AF Dan, T. D.
Ly, D.
Hewitt, S. M.
Soule, B. P.
Nowacki, A. S.
Gillespie, J.
Danforth, D. N.
Mitchell, J. B.
Camphausen, K. A.
Simone, N. L.
TI Prognostic value of CD44s in the NCI randomized trial on breast
conservation with 25-year follow-up.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
NIAID, NIH, Bethesda, MD 20892 USA.
Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA.
NCI, SAIC Frederick, Bethesda, MD 20892 USA.
NCI, Bethesda, MD 20892 USA.
NCI, Radiat Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2010
VL 28
IS 15
SU S
MA 634
PG 1
WC Oncology
SC Oncology
GA V30YT
UT WOS:000208852002468
ER
PT J
AU Deeken, JF
Mitsuyasu, RT
Little, RF
Ivy, SP
Ambinder, RF
Rudek, MA
Lee, JY
Moore, PC
Mosby, K
Dezube, BJ
AF Deeken, J. F.
Mitsuyasu, R. T.
Little, R. F.
Ivy, S. P.
Ambinder, R. F.
Rudek, M. A.
Lee, J. Y.
Moore, P. C.
Mosby, K.
Dezube, B. J.
TI Treating HIV plus patients for non-AIDS-defining cancers (NADCs) in the
era of targeted chemotherapy: An AIDS malignancy consortium study of
sunitinib in patients on ART
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Georgetown Univ, Med Ctr, Washington, DC 20007 USA.
Univ Calif Los Angeles, Care Ctr, Los Angeles, CA USA.
NCI, Rockville, MD USA.
Johns Hopkins Univ, Baltimore, MD USA.
Univ Arkansas Med Sci, Little Rock, AR 72205 USA.
EMMES Corp, Rockville, MD USA.
Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2010
VL 28
IS 15
SU S
MA TPS161
PG 1
WC Oncology
SC Oncology
GA V30YT
UT WOS:000208852002163
ER
PT J
AU Dilts, DM
Adjei, AA
Mandrekar, SJ
Buckner, JC
Minasian, LM
Rienzo, M
Ledsky, R
Massett, H
AF Dilts, D. M.
Adjei, A. A.
Mandrekar, S. J.
Buckner, J. C.
Minasian, L. M.
Rienzo, M.
Ledsky, R.
Massett, H.
TI Impact of trial development time on accruals at CCOPs: The case of the
MARVEL trial
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
Mayo Clin, Rochester, MN USA.
NCI, Bethesda, MD 20892 USA.
Rienzo & Associates, Rockville, MD USA.
AED, Washington, DC USA.
NCI, Rockville, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2010
VL 28
IS 15
SU S
MA e16505
PG 1
WC Oncology
SC Oncology
GA V30YT
UT WOS:000208852001250
ER
EF