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 TC 14 Z9 14 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 TC 23 Z9 26 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 TC 14 Z9 14 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 TC 96 Z9 101 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 TC 46 Z9 48 U1 2 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 TC 40 Z9 43 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 TC 8 Z9 8 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 TC 21 Z9 22 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 TC 60 Z9 62 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 TC 53 Z9 53 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 TC 15 Z9 15 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 TC 35 Z9 36 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 Z9 8 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 TC 21 Z9 21 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 TC 11 Z9 11 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 Z9 21 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 TC 13 Z9 13 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 TC 34 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 TC 59 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 TC 16 Z9 16 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 TC 3 Z9 4 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 TC 23 Z9 23 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 TC 25 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 TC 51 Z9 52 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 TC 33 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 Z9 74 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 TC 23 Z9 24 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 Z9 2 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 TC 2 Z9 2 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 TC 22 Z9 23 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 TC 12 Z9 12 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 TC 21 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 TC 13 Z9 13 U1 1 U2 11 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 TC 1 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 TC 11 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 TC 25 Z9 26 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 speci