FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Cretekos, CJ Wang, Y Green, ED Martin, JF Rasweiler, JJ Behringer, RR AF Cretekos, Chris J. Wang, Ying Green, Eric D. Martin, James F. Rasweiler, John J. Behringer, Richard R. TI Transcriptional regulatory sequence divergence between mouse and bat modifies forelimb length SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Developmental-Biology CY JUL 25-30, 2008 CL Univ Penn, Philadelphia, PA SP Soc Dev Biol HO Univ Penn C1 [Cretekos, Chris J.] Idaho State Univ, Dept Biol Sci, Pocatello, ID 83209 USA. [Cretekos, Chris J.; Wang, Ying; Behringer, Richard R.] Univ Texas MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX 77030 USA. [Green, Eric D.] NHGRI, Gen Technol Branch, Bethesda, MD 20892 USA. [Green, Eric D.] NHGRI, NIH, Intramural Sequencing Ctr, Bethesda, MD 20892 USA. [Martin, James F.] Texas A&M Syst Hlth Sci Ctr, Alkek Inst Biosci & Technol, Houston, TX USA. [Rasweiler, John J.] SUNY Hlth Sci Ctr, Dept Obstet & Gynecol, Brooklyn, NY 11203 USA. RI Cretekos, Chris/D-8350-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2008 VL 319 IS 2 MA 23 BP 470 EP 470 DI 10.1016/j.ydbio.2008.05.531 PG 1 WC Developmental Biology SC Developmental Biology GA 327NA UT WOS:000257734600048 ER PT J AU Yamben, I Rachel, R Copeland, N Jenkins, N Griep, A AF Yamben, Idella Rachel, R. Copeland, N. Jenkins, N. Griep, A. TI The PDZ proteins, Dlg-1 and Scrib, are required for lens fiber cell differentiation in the mouse SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Developmental-Biology CY JUL 25-30, 2008 CL Univ Penn, Philadelphia, PA SP Soc Dev Biol HO Univ Penn C1 [Yamben, Idella; Griep, A.] UW Madison, Dept Anat, Madison, WI USA. [Rachel, R.; Copeland, N.; Jenkins, N.] NCI Frederick, Mouse Canc Genet, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2008 VL 319 IS 2 MA 93 BP 496 EP 496 DI 10.1016/j.ydbio.2008.05.104 PG 1 WC Developmental Biology SC Developmental Biology GA 327NA UT WOS:000257734600118 ER PT J AU Underwood, S Williams, T Mishina, Y Lewandoski, M AF Underwood, Sangeeta Williams, Trevor Mishina, Yuji Lewandoski, Mark TI In limb development BMP and FGF signaling interact through Sproutys SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Developmental-Biology CY JUL 25-30, 2008 CL Univ Penn, Philadelphia, PA SP Soc Dev Biol HO Univ Penn C1 [Underwood, Sangeeta; Lewandoski, Mark] NCI Frederick, Canc & Dev Biol Lab, NIH, Frederick, MD USA. [Williams, Trevor] Univ Colorado, Hlth Sci Ctr, Aurora, CO USA. [Mishina, Yuji] NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2008 VL 319 IS 2 MA 100 BP 498 EP 498 DI 10.1016/j.ydbio.2008.05.111 PG 1 WC Developmental Biology SC Developmental Biology GA 327NA UT WOS:000257734600125 ER PT J AU Onodera, T Sakai, T Yamada, KM AF Onodera, Tomohiro Sakai, Takayoshi Yamada, Kenneth M. TI Cleftin: A novel fibronectin-induced gene that promotes branching morphogenesis SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Developmental-Biology CY JUL 25-30, 2008 CL Univ Penn, Philadelphia, PA SP Soc Dev Biol HO Univ Penn C1 [Onodera, Tomohiro; Yamada, Kenneth M.] NIDCR, NIH, Bethesda, MD USA. [Sakai, Takayoshi] Osaka Univ, Oral Facial Disorders, Osaka, Japan. RI Onodera, Tomohiro/G-1686-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2008 VL 319 IS 2 MA 123 BP 505 EP 505 DI 10.1016/j.ydbio.2008.05.135 PG 1 WC Developmental Biology SC Developmental Biology GA 327NA UT WOS:000257734600148 ER PT J AU Tian, Y Goss, AM Wang, Z Yamaguchi, TP Morrisey, EE AF Tian, Ying Goss, Ashley M. Wang, Zhishan Yamaguchi, Terry P. Morrisey, Edward E. TI Wnt2 signaling regulates morphogenesis of the inflow tract and atrioventricular canal during cardiac development SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Developmental-Biology CY JUL 25-30, 2008 CL Univ Penn, Philadelphia, PA SP Soc Dev Biol HO Univ Penn C1 [Tian, Ying; Goss, Ashley M.; Wang, Zhishan; Morrisey, Edward E.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Yamaguchi, Terry P.] NCI, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2008 VL 319 IS 2 MA 128 BP 506 EP 506 DI 10.1016/j.ydbio.2008.05.140 PG 1 WC Developmental Biology SC Developmental Biology GA 327NA UT WOS:000257734600153 ER PT J AU Atit, R Ohtola, J Myers, J Akhtar-Zaidi, B Zuzindlak, D Sandesara, P Mackem, S AF Atit, Radhika Ohtola, Jennifer Myers, John Akhtar-Zaidi, Batool Zuzindlak, Diana Sandesara, Pooja Mackem, Susan TI Sequential roles of Wnt signaling/beta-catenin in mouse ventral dermal development SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Developmental-Biology CY JUL 25-30, 2008 CL Univ Penn, Philadelphia, PA SP Soc Dev Biol HO Univ Penn C1 [Atit, Radhika; Ohtola, Jennifer; Myers, John; Akhtar-Zaidi, Batool; Zuzindlak, Diana; Sandesara, Pooja; Mackem, Susan] Case Western Reserve Univ, Dept Biol, Cleveland, OH 44106 USA. [Mackem, Susan] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Mackem, Susan] Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. [Mackem, Susan] Case Western Reserve Univ, Dept Dermatol, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2008 VL 319 IS 2 MA 133 BP 507 EP 508 DI 10.1016/j.ydbio.2008.05.145 PG 2 WC Developmental Biology SC Developmental Biology GA 327NA UT WOS:000257734600158 ER PT J AU Alexander, PG Bobick, BE Clark, KL Chandra, AA Tuan, RS AF Alexander, Peter G. Bobick, Brent E. Clark, Karen L. Chandra, Anisha A. Tuan, Rocky S. TI Influence of biomechanical force on joint development marker gene expression in chick embryo limb bud mesenchyme micromass cultures SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Developmental-Biology CY JUL 25-30, 2008 CL Univ Penn, Philadelphia, PA SP Soc Dev Biol HO Univ Penn C1 [Alexander, Peter G.; Bobick, Brent E.; Clark, Karen L.; Chandra, Anisha A.; Tuan, Rocky S.] NIAMS, Cartilage Biol & Orthopaed Branch, NIH, DHHS, Bethesda, MD USA. 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2008 VL 319 IS 2 MA 145 BP 510 EP 511 DI 10.1016/j.ydbio.2008.05.157 PG 2 WC Developmental Biology SC Developmental Biology GA 327NA UT WOS:000257734600170 ER PT J AU Grinblat, Y Nyholm, M Taylor, A Burgess, S AF Grinblat, Yevgenya Nyholm, Molly Taylor, Aaron Burgess, Shawn TI A role for zic genes during neural tube morphogenesis in zebrafish SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Developmental-Biology CY JUL 25-30, 2008 CL Univ Penn, Philadelphia, PA SP Soc Dev Biol HO Univ Penn C1 [Grinblat, Yevgenya; Nyholm, Molly; Taylor, Aaron] Univ Wisconsin, Madison, WI USA. [Burgess, Shawn] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2008 VL 319 IS 2 MA 160 BP 514 EP 515 DI 10.1016/j.ydbio.2008.05.172 PG 2 WC Developmental Biology SC Developmental Biology GA 327NA UT WOS:000257734600185 ER PT J AU Sargent, TD Luo, T Xu, YH AF Sargent, Thomas D. Luo, Ting Xu, Yanhua TI Inca: A novel regulator of cytoarchitecture and gene expression in vertebrate development SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Developmental-Biology CY JUL 25-30, 2008 CL Univ Penn, Philadelphia, PA SP Soc Dev Biol HO Univ Penn C1 [Sargent, Thomas D.; Luo, Ting; Xu, Yanhua] NICHD, Mol Genet Lab, NIH, Bethesda, MD 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2008 VL 319 IS 2 MA 192 BP 524 EP 524 DI 10.1016/j.ydbio.2008.05.206 PG 1 WC Developmental Biology SC Developmental Biology GA 327NA UT WOS:000257734600216 ER PT J AU Driver, EC Kelley, MW AF Driver, Elizabeth Carroll Kelley, Matthew W. TI Hedgehog signaling regulates mammalian sensory cell formation and auditory function SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Developmental-Biology CY JUL 25-30, 2008 CL Univ Penn, Philadelphia, PA SP Soc Dev Biol HO Univ Penn C1 [Driver, Elizabeth Carroll; Kelley, Matthew W.] NIDCD, Sect Dev Neurosci, NIH, Bethesda, MD USA. OI Driver, Elizabeth/0000-0002-5618-1053 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2008 VL 319 IS 2 MA 234 BP 535 EP 535 DI 10.1016/j.ydbio.2008.05.250 PG 1 WC Developmental Biology SC Developmental Biology GA 327NA UT WOS:000257734600258 ER PT J AU Puligilla, C Dabdoub, A Cheah, KS Pevny, LH Kelley, MW AF Puligilla, Chandrakala Dabdoub, A. Cheah, K. S. Pevny, L. H. Kelley, M. W. TI Sox2 as a prosensory and proneural gene in the developing mouse cochlea SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Developmental-Biology CY JUL 25-30, 2008 CL Univ Penn, Philadelphia, PA SP Soc Dev Biol HO Univ Penn C1 [Puligilla, Chandrakala; Dabdoub, A.; Kelley, M. W.] NIDCD, NIH, Bethesda, MD 20892 USA. [Cheah, K. S.] Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. [Pevny, L. H.] UNC, Chapel Hill, NC USA. NR 0 TC 0 Z9 2 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2008 VL 319 IS 2 MA 233 BP 535 EP 535 DI 10.1016/j.ydbio.2008.05.249 PG 1 WC Developmental Biology SC Developmental Biology GA 327NA UT WOS:000257734600257 ER PT J AU Hwang, YS Luo, T Xu, YH Sargent, TD AF Hwang, Yoo-Seok Luo, Ting Xu, Yanhua Sargent, Thomas D. TI Myosin-X is required for proper behavior of neural crest cells in Xenopus laevis SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Developmental-Biology CY JUL 25-30, 2008 CL Univ Penn, Philadelphia, PA SP Soc Dev Biol HO Univ Penn C1 [Hwang, Yoo-Seok; Luo, Ting; Xu, Yanhua; Sargent, Thomas D.] NICHD, Mol Genet Lab, NIH, Bethesda, MD 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2008 VL 319 IS 2 MA 248 BP 540 EP 540 DI 10.1016/j.ydbio.2008.05.264 PG 1 WC Developmental Biology SC Developmental Biology GA 327NA UT WOS:000257734600272 ER PT J AU Kohn, MJ Ullah, Z Yagi, R Vassilev, L DePamphilis, M AF Kohn, Matthew J. Ullah, Zakir Yagi, Rieko Vassilev, Lyubomir DePamphilis, Melvin TI Differentiation of trophoblast stem cells into giant cells is triggered by p57 inhibition of CDK1 activity SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Developmental-Biology CY JUL 25-30, 2008 CL Univ Penn, Philadelphia, PA SP Soc Dev Biol HO Univ Penn C1 [Kohn, Matthew J.; Ullah, Zakir; Yagi, Rieko; DePamphilis, Melvin] NICHD, Program Genom Dev, NIH, Bethesda, MD USA. [Vassilev, Lyubomir] Roche Res Ctr, Dept Discovery Oncol, Nutley, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2008 VL 319 IS 2 MA 264 BP 544 EP 545 DI 10.1016/j.ydbio.2008.05.281 PG 2 WC Developmental Biology SC Developmental Biology GA 327NA UT WOS:000257734600287 ER PT J AU Ma, XF Adelstein, RS AF Ma, Xuefei Adelstein, Robert S. TI Nonmuscle myosin II-B plays important roles in mouse heart development SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Developmental-Biology CY JUL 25-30, 2008 CL Univ Penn, Philadelphia, PA SP Soc Dev Biol HO Univ Penn C1 [Ma, Xuefei; Adelstein, Robert S.] NHLBI, LMC, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2008 VL 319 IS 2 MA 267 BP 545 EP 546 DI 10.1016/j.ydbio.2008.05.284 PG 2 WC Developmental Biology SC Developmental Biology GA 327NA UT WOS:000257734600290 ER PT J AU Dey-Guha, I Mukhopadhyay, M Westphal, H AF Dey-Guha, Ipsita Mukhopadhyay, Mahua Westphal, Heiner TI Role of Ldb1 in tissue homeostasis of the adult mouse SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Developmental-Biology CY JUL 25-30, 2008 CL Univ Penn, Philadelphia, PA SP Soc Dev Biol HO Univ Penn C1 [Dey-Guha, Ipsita; Mukhopadhyay, Mahua; Westphal, Heiner] NICHD, LMGD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2008 VL 319 IS 2 MA 292 BP 555 EP 555 DI 10.1016/j.ydbio.2008.05.312 PG 1 WC Developmental Biology SC Developmental Biology GA 327NA UT WOS:000257734600313 ER PT J AU Makarev, E Westphal, H AF Makarev, Evgeny Westphal, Heiner TI Islet1 and its cofactor LDB1 express in the mouse intestinal epithelium SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Developmental-Biology CY JUL 25-30, 2008 CL Univ Penn, Philadelphia, PA SP Soc Dev Biol HO Univ Penn C1 [Makarev, Evgeny; Westphal, Heiner] NIH, Lab Mammalian Genes & Dev, Bethesda, MD 20892 USA. 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2008 VL 319 IS 2 MA 293 BP 555 EP 555 DI 10.1016/j.ydbio.2008.05.313 PG 1 WC Developmental Biology SC Developmental Biology GA 327NA UT WOS:000257734600314 ER PT J AU Pei, WH Bernardini, I Wassif, C Porter, F Anikster, Y Huizing, M Feldman, B AF Pei, Wuhong Bernardini, Isa Wassif, Christopher Porter, Forbes Anikster, Yair Huizing, Marjan Feldman, Benjamin TI Seeking the biochemical basis of type III 3-methylglutaconic aciduria through zebrafish models SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Developmental-Biology CY JUL 25-30, 2008 CL Univ Penn, Philadelphia, PA SP Soc Dev Biol HO Univ Penn C1 [Pei, Wuhong; Bernardini, Isa; Wassif, Christopher; Porter, Forbes; Huizing, Marjan; Feldman, Benjamin] Natl Inst Hlth, Bethesda, MD USA. [Anikster, Yair] Tel Aviv Univ, Sackler Sch Med, Chaim Sheba Med Ctr, Tel Hashomer, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2008 VL 319 IS 2 MA 316 BP 562 EP 562 DI 10.1016/j.ydbio.2008.05.337 PG 1 WC Developmental Biology SC Developmental Biology GA 327NA UT WOS:000257734600337 ER PT J AU Brody, T Kuzin, A Kundu, M Ross, J Odenwald, W AF Brody, Thomas Kuzin, Alexander Kundu, Mukta Ross, Jermaine Odenwald, Ward TI Discovery and functional analysis of shared regulatory elements in neuroblast enhancers SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Developmental-Biology CY JUL 25-30, 2008 CL Univ Penn, Philadelphia, PA SP Soc Dev Biol HO Univ Penn C1 [Brody, Thomas; Kuzin, Alexander; Kundu, Mukta; Ross, Jermaine; Odenwald, Ward] NINDS, Neural Cell Fate Determinants Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2008 VL 319 IS 2 MA 331 BP 567 EP 567 DI 10.1016/j.ydbio.2008.05.354 PG 1 WC Developmental Biology SC Developmental Biology GA 327NA UT WOS:000257734600352 ER PT J AU Snir, M Brown, J Feldman, B AF Snir, Mirit Brown, Jamie Feldman, Benjamin TI Repression of P53 downstream of dual specificity phosphatase 4 is essential for late endoderm specification in early zebrafish development SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Developmental-Biology CY JUL 25-30, 2008 CL Univ Penn, Philadelphia, PA SP Soc Dev Biol HO Univ Penn C1 [Snir, Mirit; Brown, Jamie; Feldman, Benjamin] NHGRI, Med Genet Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2008 VL 319 IS 2 MA 342 BP 570 EP 570 DI 10.1016/j.ydbio.2008.05.365 PG 1 WC Developmental Biology SC Developmental Biology GA 327NA UT WOS:000257734600363 ER PT J AU Wan, LB Pan, H Cheng, Y Ma, J Fedoriw, A Lobanenkov, V Latham, KE Schultz, RM Bartolomei, MS AF Wan, Le-Ben Pan, Hua Cheng, Yong Ma, Jun Fedoriw, Andrew Lobanenkov, Victor Latham, Keith E. Schultz, Richard M. Bartolomei, Marisa S. TI Maternal effects of CTCF, a multifunctional epigenetic regulator SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Developmental-Biology CY JUL 25-30, 2008 CL Univ Penn, Philadelphia, PA SP Soc Dev Biol HO Univ Penn C1 [Wan, Le-Ben; Fedoriw, Andrew; Schultz, Richard M.; Bartolomei, Marisa S.] Univ Penn, Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. [Pan, Hua; Ma, Jun] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA. [Cheng, Yong; Latham, Keith E.] Temple Univ, Sch Med, Fels Inst Canc Res & Mol Biol, Philadelphia, PA 19140 USA. [Cheng, Yong; Latham, Keith E.] Temple Univ, Sch Med, Dept Biochem, Philadelphia, PA 19140 USA. [Lobanenkov, Victor] NIAID, Immunopathol Lab, NIH, Rockville, MD 20852 USA. OI Lobanenkov, Victor/0000-0001-6665-3635 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2008 VL 319 IS 2 MA 346 BP 571 EP 571 DI 10.1016/j.ydbio.2008.05.369 PG 1 WC Developmental Biology SC Developmental Biology GA 327NA UT WOS:000257734600367 ER PT J AU Song, H Kispert, A Yang, YZ AF Song, Hai Kispert, Andreas Yang, Yingzi TI Redundant function of Wnt5a and Wnt11 in somitogenesis and anteroposterior axis elongation SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Developmental-Biology CY JUL 25-30, 2008 CL Univ Penn, Philadelphia, PA SP Soc Dev Biol HO Univ Penn C1 [Song, Hai; Yang, Yingzi] NHGRI, GDRB, Bethesda, MD 20892 USA. [Kispert, Andreas] Hannover Med Sch, Inst Mol Biol, D-30625 Hannover, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2008 VL 319 IS 2 MA 393 BP 584 EP 585 DI 10.1016/j.ydbio.2008.05.417 PG 2 WC Developmental Biology SC Developmental Biology GA 327NA UT WOS:000257734600413 ER PT J AU Mishina, Y Kaartinen, V Komatsu, Y AF Mishina, Yuji Kaartinen, Vesa Komatsu, Yoshihiro TI BMP signaling through ACVR1 is crucial for establishment of the left-right asymmetry via proper formation of node cilia in the mouse SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Developmental-Biology CY JUL 25-30, 2008 CL Univ Penn, Philadelphia, PA SP Soc Dev Biol HO Univ Penn C1 [Mishina, Yuji; Komatsu, Yoshihiro] Natl Inst Environm Hlth Sci, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC USA. [Kaartinen, Vesa] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Kaartinen, Vesa] Childrens Hosp Los Angeles, Res Inst, Dept Pathol, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2008 VL 319 IS 2 MA 394 BP 585 EP 585 DI 10.1016/j.ydbio.2008.05.418 PG 1 WC Developmental Biology SC Developmental Biology GA 327NA UT WOS:000257734600414 ER PT J AU Garg, A Deng, H Kuzin, A Brody, T Simmonds, A Odenwald, W Bell, J AF Garg, Ankush Deng, Hua Kuzin, Alexander Brody, Tom Simmonds, Andrew Odenwald, Ward Bell, John TI Nerfin-1: A novel binding partner of scalloped SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Developmental-Biology CY JUL 25-30, 2008 CL Univ Penn, Philadelphia, PA SP Soc Dev Biol HO Univ Penn C1 [Garg, Ankush; Deng, Hua; Odenwald, Ward] Univ Alberta, Dept Biol Sci, Edmonton, AB, Canada. [Kuzin, Alexander; Brody, Tom] Natl Inst Hlth, Neural Cell Fate Determinants Sect, Bethesda, MD USA. [Simmonds, Andrew] Univ Alberta, Dept Cell Biol, Edmonton, AB, Canada. RI Simmonds, Andrew /D-3675-2009 NR 0 TC 0 Z9 0 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2008 VL 319 IS 2 MA 407 BP 589 EP 589 DI 10.1016/j.ydbio.2008.05.485 PG 1 WC Developmental Biology SC Developmental Biology GA 327NA UT WOS:000257734600427 ER PT J AU Hwang, L Mehrani, T Millar, SE Morasso, MI AF Hwang, Loonsung Mehrani, Taraneh Millar, Sarah E. Morasso, Maria I. TI The role of Dlx3 in hair development SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Developmental-Biology CY JUL 25-30, 2008 CL Univ Penn, Philadelphia, PA SP Soc Dev Biol HO Univ Penn C1 [Hwang, Loonsung; Mehrani, Taraneh; Morasso, Maria I.] NIAMS, Dev Skin Biol Unit, NIH, Bethesda, MD 20892 USA. [Millar, Sarah E.] Univ Penn, Sch Med, Dept Dermatol & Cell & Dev Biol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2008 VL 319 IS 2 MA 432 BP 595 EP 596 DI 10.1016/j.ydbio.2008.05.509 PG 2 WC Developmental Biology SC Developmental Biology GA 327NA UT WOS:000257734600451 ER PT J AU Duverger, O Lee, D Hassan, MQ Chen, SX Jaisser, F Lian, JB Morasso, MI AF Duverger, Olivier Lee, Delia Hassan, Mohammad Q. Chen, Susie X. Jaisser, Frederic Lian, Jane B. Morasso, Maria I. TI Molecular consequences of a frameshifted Dlx3 mutant leading to Tricho-Dento-Osseous syndrome SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Developmental-Biology CY JUL 25-30, 2008 CL Univ Penn, Philadelphia, PA SP Soc Dev Biol HO Univ Penn C1 [Duverger, Olivier; Lee, Delia; Chen, Susie X.] NIAMS, Dev Skin Biol Unit, NIH, Bethesda, MD USA. [Hassan, Mohammad Q.; Lian, Jane B.] UMass Med Sch, Worcester, MA USA. [Jaisser, Frederic] Coll France, INSERM, U772, F-75231 Paris, France. 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2008 VL 319 IS 2 MA 433 BP 596 EP 596 DI 10.1016/j.ydbio.2008.05.510 PG 1 WC Developmental Biology SC Developmental Biology GA 327NA UT WOS:000257734600452 ER PT J AU Naiche, LA Ripla, A Papaioannou, VE AF Naiche, L. A. Ripla, Arora Papaioannou, Virginia E. TI The identity and fate of Tbx4-expressing cells reveal previously unknown developmental decisions in the allantois, limb, and proctodeum SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Developmental-Biology CY JUL 25-30, 2008 CL Univ Penn, Philadelphia, PA SP Soc Dev Biol HO Univ Penn C1 [Naiche, L. A.] NCI, Frederick, MD 21701 USA. [Ripla, Arora; Papaioannou, Virginia E.] Columbia Univ, Dept Genet & Dev, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2008 VL 319 IS 2 MA 435 BP 596 EP 596 DI 10.1016/j.ydbio.2008.05.512 PG 1 WC Developmental Biology SC Developmental Biology GA 327NA UT WOS:000257734600454 ER PT J AU Zhu, JJ Nakamura, E Nguyen, MT Bao, XZ Mackem, S AF Zhu, Jianjian Nakamura, Eiichiro Nguyen, Minh-Thanh Bao, Xiaozhong Mackem, Susan TI Dual, separable roles of Sonic Hedgehog in limb bud patterning and expansion SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Developmental-Biology CY JUL 25-30, 2008 CL Univ Penn, Philadelphia, PA SP Soc Dev Biol HO Univ Penn C1 [Zhu, Jianjian; Nakamura, Eiichiro; Nguyen, Minh-Thanh; Bao, Xiaozhong; Mackem, Susan] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2008 VL 319 IS 2 MA 441 BP 598 EP 598 DI 10.1016/j.ydbio.2008.05.518 PG 1 WC Developmental Biology SC Developmental Biology GA 327NA UT WOS:000257734600460 ER PT J AU Cohen, T Westphal, H AF Cohen, Tsadok Westphal, Heiner TI The role of Ldb complexes in lens development SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Developmental-Biology CY JUL 25-30, 2008 CL Univ Penn, Philadelphia, PA SP Soc Dev Biol HO Univ Penn C1 [Cohen, Tsadok; Westphal, Heiner] NICHD, LMGD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2008 VL 319 IS 2 MA 449 BP 600 EP 601 DI 10.1016/j.ydbio.2008.05.430 PG 2 WC Developmental Biology SC Developmental Biology GA 327NA UT WOS:000257734600468 ER PT J AU Phillips, MD Bogen, D Westphal, H AF Phillips, Matthew D. Bogen, Dominik Westphal, Heiner TI The LIM-domain binding protein Ldb1 is required for proper endocardial cushion formation during heart development in Mus musculus SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Developmental-Biology CY JUL 25-30, 2008 CL Univ Penn, Philadelphia, PA SP Soc Dev Biol HO Univ Penn C1 [Phillips, Matthew D.; Bogen, Dominik; Westphal, Heiner] NICHD, Lab Mammalian Genes & Dev, PGD, NIH, Bethesda, MD USA. 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2008 VL 319 IS 2 MA 454 BP 602 EP 602 DI 10.1016/j.ydbio.2008.05.435 PG 1 WC Developmental Biology SC Developmental Biology GA 327NA UT WOS:000257734600473 ER PT J AU Goss, AM Tian, Y Wang, ZS Yamaguchi, T Morrisey, E AF Goss, Ashley M. Tian, Ying Wang, Zhishan Yamaguchi, Terry Morrisey, Edward TI Wnt2a/2b are required for lung specification and development through activation of canonical signaling. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Developmental-Biology CY JUL 25-30, 2008 CL Univ Penn, Philadelphia, PA SP Soc Dev Biol HO Univ Penn C1 [Goss, Ashley M.; Tian, Ying; Wang, Zhishan; Morrisey, Edward] Univ Penn, Dept Med, Sch Med, Philadelphia, PA 19104 USA. [Yamaguchi, Terry] NCI, Canc & Dev Biol Lab, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2008 VL 319 IS 2 MA 471 BP 606 EP 606 DI 10.1016/j.ydbio.2008.05.452 PG 1 WC Developmental Biology SC Developmental Biology GA 327NA UT WOS:000257734600490 ER PT J AU Wang, A Ma, X Kawamoto, S Adelstein, RS AF Wang, Aibing Ma, X. Kawamoto, S. Adelstein, R. S. TI Understanding the function of nonmuscle myosin II-A (NM II-A) in vivo SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Developmental-Biology CY JUL 25-30, 2008 CL Univ Penn, Philadelphia, PA SP Soc Dev Biol HO Univ Penn C1 [Wang, Aibing; Ma, X.; Kawamoto, S.; Adelstein, R. S.] NHLBI, LMC, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2008 VL 319 IS 2 MA 481 BP 609 EP 609 DI 10.1016/j.ydbio.2008.05.462 PG 1 WC Developmental Biology SC Developmental Biology GA 327NA UT WOS:000257734600500 ER PT J AU Gilchrist, DA Nechaev, S Lee, CH Ghosh, SKB Collins, JB Li, LP Gilmour, DS Adelman, K AF Gilchrist, Daniel A. Nechaev, Sergei Lee, Chanhyo Ghosh, Saikat Kumar B. Collins, Jennifer B. Li, Leping Gilmour, David S. Adelman, Karen TI NELF-mediated stalling of Pol II can enhance gene expression by blocking promoter-proximal nucleosome assembly SO GENES & DEVELOPMENT LA English DT Article DE gene expression; transcription elongation; polymerase stalling; chromatin structure ID RNA-POLYMERASE-II; TRANSCRIPTION ELONGATION-FACTOR; HEAT-SHOCK GENES; IMMUNODEFICIENCY-VIRUS TRANSCRIPTION; CLEAVAGE FACTOR TFIIS; DROSOPHILA-MELANOGASTER; IN-VIVO; P-TEFB; SACCHAROMYCES-CEREVISIAE; CHROMATIN-STRUCTURE AB The Negative Elongation Factor (NELF) is a transcription regulatory complex that induces stalling of RNA polymerase II (Pol II) during early transcription elongation and represses expression of several genes studied to date, including Drosophila Hsp70, mammalian proto-oncogene junB, and HIV RNA. To determine the full spectrum of NELF target genes in Drosophila, we performed a microarray analysis of S2 cells depleted of NELF and discovered that NELF RNAi affects many rapidly inducible genes involved in cellular responses to stimuli. Surprisingly, only one-third of NELF target genes were, like Hsp70, up-regulated by NELF-depletion, whereas the majority of target genes showed decreased expression levels upon NELF RNAi. Our data reveal that the presence of stalled Pol II at this latter group of genes enhances gene expression by maintaining a permissive chromatin architecture around the promoter-proximal region, and that loss of Pol II stalling at these promoters is accompanied by a significant increase in nucleosome occupancy and a decrease in histone H3 Lys 4 trimethylation. These findings identify a novel, positive role for stalled Pol II in regulating gene expression and suggest that there is a dynamic interplay between stalled Pol II and chromatin structure. C1 [Gilchrist, Daniel A.; Nechaev, Sergei; Adelman, Karen] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. [Lee, Chanhyo; Ghosh, Saikat Kumar B.; Gilmour, David S.] Penn State Univ, Dept Biochem & Mol Biol, Ctr Gene Regulat, University Pk, PA 16802 USA. [Collins, Jennifer B.; Adelman, Karen] NIEHS, Microarray Grp, NIH, Res Triangle Pk, NC 27709 USA. [Li, Leping] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. RP Adelman, K (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. EM adelmank@niehs.nih.gov OI Gilchrist, Daniel/0000-0003-1668-2790 FU Intramural NIH HHS; NIEHS NIH HHS [Z01 ES101987]; NIGMS NIH HHS [GM47477, R01 GM047477] NR 50 TC 145 Z9 145 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JUL 15 PY 2008 VL 22 IS 14 BP 1921 EP 1933 DI 10.1101/gad.1643208 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 326FI UT WOS:000257643400008 PM 18628398 ER PT J AU Matera, I Watkins-Chow, DE Loftus, SK Hou, L Incao, A Silver, DL Rivas, C Elliott, EC Baxter, LL Pavan, WJ AF Matera, Ivana Watkins-Chow, Dawn E. Loftus, Stacie K. Hou, Ling Incao, Arturo Silver, Debra L. Rivas, Cecelia Elliott, Eugene C. Baxter, Laura L. Pavan, William J. TI A sensitized mutagenesis screen identifies Gli3 as a modifier of Sox10 neurocristopathy SO HUMAN MOLECULAR GENETICS LA English DT Article ID CREST-DERIVED MELANOCYTES; GREIG CEPHALOPOLYSYNDACTYLY SYNDROME; WAARDENBURG-HIRSCHSPRUNG-DISEASE; PALLISTER-HALL SYNDROME; WNT SIGNALING PATHWAY; NEURAL CREST; TRANSCRIPTION FACTOR; SONIC HEDGEHOG; ENDOTHELIN-3 GENE; SYNDROME TYPE-2 AB Haploinsufficiency for the transcription factor SOX10 is associated with the pigmentary deficiencies of Waardenburg syndrome (WS) and is modeled in Sox10 haploinsufficient mice (Sox10(LacZ/+)). As genetic background affects WS severity in both humans and mice, we established an N-ethyl-N-nitrosourea (ENU) mutagenesis screen to identify modifiers that increase the phenotypic severity of Sox10(LacZ/+) mice. Analysis of 230 pedigrees identified three modifiers, named modifier of Sox10 neurocristopathies (Mos1, Mos2 and Mos3). Linkage analysis confirmed their locations on mouse chromosomes 13, 4 and 3, respectively, within regions distinct from previously identified WS loci. Positional candidate analysis of Mos1 identified a truncation mutation in a hedgehog(HH)-signaling mediator, GLI-Kruppel family member 3 (Gli3). Complementation tests using a second allele of Gli3 (Gli3(Xt-J)) confirmed that a null mutation of Gli3 causes the increased hypopigmentation in Sox10(LacZ/+);Gli3(Mos1/+) double heterozygotes. Early melanoblast markers (Mitf, Sox10, Dct, and Si) are reduced in Gli3(Mos1/Mos1) embryos, indicating that loss of GLI3 signaling disrupts melanoblast specification. In contrast, mice expressing only the GLI3 repressor have normal melanoblast specification, indicating that the full-length GLI3 activator is not required for specification of neural crest to the melanocyte lineage. This study demonstrates the feasibility of sensitized screens to identify disease modifier loci and implicates GLI3 and other HH signaling components as modifiers of human neurocristopathies. C1 [Pavan, William J.] NHGRI, Mouse Embryol Sect, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Matera, Ivana] Inst G Gaslini, Genet Mol Lab, Genoa, Italy. RP Pavan, WJ (reprint author), NHGRI, Mouse Embryol Sect, Genet Dis Res Branch, NIH, Bldg 49,Room 4A82,49 Convent Dr, Bethesda, MD 20892 USA. EM bpavan@mail.nih.gov OI Hou, Ling/0000-0003-0705-8099; Watkins-Chow, Dawn/0000-0002-4355-0868 FU Intramural NIH HHS; NHGRI NIH HHS [N01 HG-65403]; NICHD NIH HHS [U01 HD43430] NR 66 TC 25 Z9 26 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 JUL 15 PY 2008 VL 17 IS 14 BP 2118 EP 2131 DI 10.1093/hmg/ddn110 PG 14 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 319RK UT WOS:000257181300005 PM 18397875 ER PT J AU Yang, JL Qu, XJ Yu, Y Kohn, EC Friedlander, ML AF Yang, Jia-Lin Qu, Xian-Jun Yu, Yan Kohn, Elise C. Friedlander, Michael L. TI Selective sensitivity to carboxyamidotriazole by human tumor cell lines with DNA mismatch repair deficiency SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE carboxyamidotriazole; calcium channel blocker; DNA mismatch repair; cancer therapy; apoptosis ID NONPOLYPOSIS COLORECTAL-CANCER; SIGNAL-TRANSDUCTION INHIBITOR; PHASE-II; MICRONIZED FORMULATION; GROWTH-INHIBITION; DRUG-RESISTANCE; COLON-CANCER; CYCLE ARREST; HEREDITARY; TRIAZOLE AB We have previously reported that high-dose nifedipine had a selective antiproliferative effect on colon cancer cell lines deficient in DNA mismatch repair (MMR). We hypothesized that carboxyamidotriazole (CAI), a calcium channel blocker, would also have a selective inhibitory effect on colon cancer cell lines with DNA MMR deficiency. In addition, we speculated that this effect may also be seen in cell lines deficient in DNA MMR derived from other tumor types. Fourteen human cancer cell lines with and without DNA MMR derived from carcinomas of the colon, bladder, ovary and prostate were treated with CAI, vehicle or control drugs (nifedipine and 5-flurouracil). The effect of treatment on growth inhibition, invasion, apoptosis and cell cycle progression was assessed. Selective sensitivity to CAI was observed in all cancer cell lines deficient in MMR. Compared with the MMR-proficient cells, the matched deficient cells were significantly more sensitive to the growth inhibitory effect of CAI and nifedipine, but less sensitive to 5-flurouracil. CAI significantly inhibited the invasive ability of MMR-deficient cancer cells compared to 5-flurouracil. CAI induced more apoptosis but similar level of G(2)/M arrest in MMR (hMLH1- or hMSH6-)-deficient colon cancer cells than MMR-proficient counterparts. CAI selectively inhibits proliferation and invasion in MMR-deficient human cancer cell lines. The antitumor effect is at least partly explained by G2/M cell cycle arrest and induction of apoptosis. These findings may have clinical implications directing clinical trials in selectively targeted patients with DNA MMR tumors. (C) 2008 Wiley-Liss, Inc. C1 [Yang, Jia-Lin] Univ New S Wales, Prince Wales Clin Sch, Oncol Res Ctr, Surg Oncol Res Grp, Sydney, NSW, Australia. [Qu, Xian-Jun] Shandong Univ, Dept Pharmacol, Coll Pharm, Jinan, Peoples R China. [Yu, Yan] Univ New S Wales, Prince Wales Clin Sch, Orthopaed Res Lab, Sydney, NSW, Australia. [Kohn, Elise C.] Natl Canc Inst, Natl Inst Hlth, Pathol Lab, Bethesda, MD USA. [Friedlander, Michael L.] Univ New S Wales, Prince Wales Hosp, Dept Med Oncol, Fac Med, Sydney, NSW, Australia. RP Yang, JL (reprint author), Prince Wales Hosp, Oncol Res Ctr, Surg Oncol Res Grp, Randwick, NSW 2031, Australia. EM j.yang@unsw.edu.au RI friedlander, michael/G-3490-2013; Yang, Jia Lin/B-9866-2014 OI friedlander, michael/0000-0002-6488-0604; Yang, Jia Lin/0000-0003-1046-7387 NR 33 TC 7 Z9 8 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 15 PY 2008 VL 123 IS 2 BP 258 EP 263 DI 10.1002/ijc.23535 PG 6 WC Oncology SC Oncology GA 313SM UT WOS:000256760300003 PM 18464258 ER PT J AU Ramus, SJ Vierkant, RA Johnatty, SE Pike, MC Van Den Berg, DJ Wu, AH Pearce, CL Menon, U Gentry-Maharaj, A Gayther, SA DiCioccio, RA McGuire, V Whittemore, AS Song, H Easton, DF Pharoah, PDP Garcia-Closas, M Chanock, S Lissowska, J Brinton, L Terry, KL Cramer, DW Tworoger, SS Hankinson, SE Berchuck, A Moorman, PG Schildkraut, JM Cunningham, JM Liebow, M Kjaer, SK Hogdall, E Hogdall, C Blaakaer, J Ness, RB Moysich, KB Edwards, RP Carney, ME Lurie, G Goodman, MT Wang-Gohrke, S Kropp, S Chang-Claude, J Webb, PM Chen, X Beesley, J Chenevix-Trench, G Goode, EL AF Ramus, Susan J. Vierkant, Robert A. Johnatty, Sharon E. Pike, Malcolm C. Van Den Berg, David J. Wu, Anna H. Pearce, Celeste Leigh Menon, Usha Gentry-Maharaj, Aleksandra Gayther, Simon A. DiCioccio, Richard A. McGuire, Valerie Whittemore, Alice S. Song, Honglin Easton, Douglas F. Pharoah, Paul D. P. Garcia-Closas, Montserrat Chanock, Stephen Lissowska, Jolanta Brinton, Louise Terry, Kathryn L. Cramer, Daniel W. Tworoger, Shelley S. Hankinson, Susan E. Berchuck, Andrew Moorman, Patricia G. Schildkraut, Joellen M. Cunningham, Julie M. Liebow, Mark Kjaer, Susanne Krueger Hogdall, Estrid Hogdall, Claus Blaakaer, Jan Ness, Roberta B. Moysich, Kirsten B. Edwards, Robert P. Carney, Michael E. Lurie, Galina Goodman, Marc T. Wang-Gohrke, Shan Kropp, Silke Chang-Claude, Jenny Webb, Penelope M. Chen, Xiaoqing Beesley, Jonathan Chenevix-Trench, Georgia Goode, Ellen L. CA Australian Ovarian Canc Study Grp Australian Canc Study Ovarian Canc Ovarian Canc Assoc Consortium OCAC TI Consortium analysis of 7 candidate SNPs for ovarian cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE association study; neoplasms; ovarian cancer; replication; single nucleotide polymorphism ID SINGLE-NUCLEOTIDE POLYMORPHISMS; GENOME-WIDE ASSOCIATION; GROWTH-FACTOR-BETA; BREAST-CANCER; COMMON VARIANT; SUSCEPTIBILITY GENE; COLORECTAL-CANCER; EPITHELIAL-CELLS; REDUCED RISK; CASP8 GENE AB The Ovarian Cancer Association Consortium selected 7 candidate single nucleotide polymorphisms (SNPs), for which there is evidence from previous studies of an association with variation in ovarian cancer or breast cancer risks. The SNPs selected for analysis were F31I (rs2273535) in AURKA, N372H (rs144848) in BRCA2, rs2854344 in intron 17 of RB1, rs2811712 5' flanking CDKN2A, rs523349 in the 3' UTR of SRD5A2, D302H (rs1045485) in CASP8 and L10P (rs1982073) in TGFB1. Fourteen studies genotyped 4,624 invasive epithelial ovarian cancer cases and 8,113 controls of white non-Hispanic origin. A marginally significant association was found for RB1 when all studies were included [ordinal odds ratio (OR) 0.88 (95% confidence interval (CI) 0.79-1.00) p = 0.041 and dominant OR 0.87 (95% CI 0.76-0.98) p = 0.025]; when the studies that originally suggested an association were excluded, the result was suggestive although no longer statistically significant (ordinal OR 0.92, 95% CI 0.79-1.06). This SNP has also been shown to have an association with decreased risk in breast cancer. There was a suggestion of an association for AURKA, when one study that caused significant study heterogeneity was excluded [ordinal OR 1.10 (95% CI 1.01-1.20) p = 0.027; dominant OR 1.12 (95% CI 1.01-1.24) p = 0.03]. The other 5 SNPs in BRCA2, CDKN2A, SRD5A2, CASP8 and TGFB1 showed no association with ovarian cancer risk; given the large sample size, these results can also be considered to be informative. These null results for SNPs identified from relatively large initial studies shows the importance of replicating associations by a consortium approach. (C) 2008 Wiley-Liss, Inc. C1 [Vierkant, Robert A.; Cunningham, Julie M.; Liebow, Mark; Goode, Ellen L.] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Ramus, Susan J.; Gayther, Simon A.] UCL, EGA Inst Womens Hlth, Translat Res Lab, London, England. [Johnatty, Sharon E.; Webb, Penelope M.; Chen, Xiaoqing; Beesley, Jonathan; Chenevix-Trench, Georgia; Australian Ovarian Canc Study Grp; Australian Canc Study Ovarian Canc] Queensland Inst Med Res, Post Off Royal Brisbane Hosp, Brisbane, Qld, Australia. [Pike, Malcolm C.; Van Den Berg, David J.; Wu, Anna H.; Pearce, Celeste Leigh] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Menon, Usha; Gentry-Maharaj, Aleksandra] UCL, EGA Inst Womens Hlth, Gynaecol Canc Res Ctr, London, England. [DiCioccio, Richard A.; Moysich, Kirsten B.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [McGuire, Valerie; Whittemore, Alice S.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Song, Honglin; Pharoah, Paul D. P.] Univ Cambridge, Strangeways Res Lab, Canc Res United Kingdom Dept Oncol, Cambridge, England. [Easton, Douglas F.] Univ Cambridge, Strangeways Res Lab, Canc Res United Kingdom Genet Epidemiol Unit, Cambridge, England. [Garcia-Closas, Montserrat; Chanock, Stephen; Brinton, Louise] Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD USA. [Lissowska, Jolanta] Ctr Canc, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Lissowska, Jolanta] M Sklodowska Curie Inst Oncol, Warsaw, Poland. [Terry, Kathryn L.; Cramer, Daniel W.] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. [Tworoger, Shelley S.; Hankinson, Susan E.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Tworoger, Shelley S.; Hankinson, Susan E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Moorman, Patricia G.; Schildkraut, Joellen M.] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. [Kjaer, Susanne Krueger; Hogdall, Estrid] Danish Canc Soc, Copenhagen, Denmark. [Hogdall, Claus] Univ Copenhagen, Juliane Marie Ctr, Rigshosp, Copenhagen, Denmark. [Blaakaer, Jan] Aarhus Univ Hosp, Skejby, Denmark. [Ness, Roberta B.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Edwards, Robert P.] Magee Womens Hosp, Pittsburgh, PA USA. [Carney, Michael E.; Lurie, Galina; Goodman, Marc T.] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA. [Wang-Gohrke, Shan] Univ Ulm, Ulm, Germany. [Kropp, Silke; Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Australian Ovarian Canc Study Grp] Peter MacCallum Canc Inst, Melbourne, Vic 3000, Australia. [Berchuck, Andrew] Duke Univ, Ctr Med, Dept Obstet & Gynecol, Durham, NC USA. RP Goode, EL (reprint author), Mayo Clin, Coll Med, Dept Hlth Sci Res, 200 1st St SW, Rochester, MN 55905 USA. EM egoode@mayo.edu RI friedlander, michael/G-3490-2013; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; Bowtell, David/H-1007-2016; Susan, Ramus/C-1607-2008; Gentry-Maharaj, Aleksandra/C-1788-2008; Menon, Usha/C-4716-2008; Webb, Penelope/D-5736-2013; Whiteman, David/P-2728-2014; Wyld, David/B-8893-2015 OI Tworoger, Shelley/0000-0002-6986-7046; Ramus, Susan/0000-0003-0005-7798; Quinn, Michael/0000-0003-0694-3870; Lissowska, Jolanta/0000-0003-2695-5799; Phillips, Kelly-Anne/0000-0002-0475-1771; Beith, Jane/0000-0002-4946-2789; friedlander, michael/0000-0002-6488-0604; Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Bowtell, David/0000-0001-9089-7525; Webb, Penelope/0000-0003-0733-5930; Whiteman, David/0000-0003-2563-9559; Kjaer, Susanne/0000-0002-8347-1398; Vierkant, Robert/0000-0001-6242-5221; Wyld, David/0000-0001-9523-4333 FU Cancer Research UK [10118]; NCI NIH HHS [R01 CA063464, 1-R01-CA76016, CA015083, CA122443, CA14089, CA16056, CA17054, CA58598, CA61132, CA63464, CA71766, K07 CA080668, K07-CA80668, N01 CA015083, N01 PC035137, N01 PC067010, N01-CN-67001, P01 CA017054, P30 CA014089, P30 CA015083, P30 CA016056, R01 CA058598, R01 CA058598-10, R01 CA076016, R01 CA095023, R01 CA122443, R01CA095023, R03 CA113148, R03-CA113148, U01 CA063464] NR 43 TC 55 Z9 57 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 15 PY 2008 VL 123 IS 2 BP 380 EP 388 DI 10.1002/ijc.23448 PG 9 WC Oncology SC Oncology GA 313SM UT WOS:000256760300018 PM 18431743 ER PT J AU King, LJ Anderson, LR Blackmore, CG Blackwell, MJ Lautner, EA Marcus, LC Meyer, TE Monath, TP Nave, JE Ohle, J Pappaioanou, M Sobota, J Stokes, WS Davis, RM Glasser, JH Mahr, RK AF King, Lonnie J. Anderson, Larry R. Blackmore, Carina G. Blackwell, Michael J. Lautner, Elizabeth A. Marcus, Leonard C. Meyer, Travis E. Monath, Thomas P. Nave, James E. Ohle, Joerg Pappaioanou, Marguerite Sobota, Justin Stokes, William S. Davis, Ronald M. Glasser, Jay H. Mahr, Roger K. TI Executive summary of the AVMA One Health Initiative Task Force report SO JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Editorial Material C1 [King, Lonnie J.] Ctr Dis Control & Prevent, Natl Ctr Zoonot Vector Borne & Enter Dis, Atlanta, GA 30329 USA. [Anderson, Larry R.] Family Care Ctr, Wellington, KS USA. [Blackmore, Carina G.] Florida Dept Hlth, Off Environm Publ Hlth Med, Tallahassee, FL USA. [Blackwell, Michael J.] LLC, Knoxville, TN USA. [Lautner, Elizabeth A.] USDA, Anim & Plant Hlth Inspect Serv, Natl Vet Services Lab, Vet Serv, Ames, IA USA. [Marcus, Leonard C.] Travelers Hlth Immunizat Serv, Newton, MA USA. [Marcus, Leonard C.] Tufts Univ, Cummings Sch Vet Med, Dept Environm & Populat Hlth, North Grafton, MA USA. [Meyer, Travis E.] Penn State Univ, Coll Med, Hershey, PA USA. [Monath, Thomas P.] Harvard Univ, Pandem & Biodefense Fund, Cambridge, MA 02138 USA. [Nave, James E.] Tropicana Anim Hosp, Las Vegas, NV USA. [Ohle, Joerg] Bayer Anim Hlth, Shawnee Mission, KS USA. [Pappaioanou, Marguerite] Assoc Amer Vet Med Coll, Washington, DC USA. [Sobota, Justin] Univ Florida, Coll Vet Med, Gainesville, FL USA. [Stokes, William S.] US PHS, Washington, DC USA. [Stokes, William S.] NIEHS, Natl Toxicol Program, Interagency Ctr Evaluat Alternat Toxicol Methods, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. [Davis, Ronald M.] Amer Med Assoc, Chicago, IL 60610 USA. [Glasser, Jay H.] Amer Publ Hlth Assoc, Washington, DC USA. [Mahr, Roger K.] Amer Vet Med Assoc, Schaumburg, IL USA. [Nave, James E.] Amer Vet Med Assoc, Schaumburg, IL 60173 USA. RP King, LJ (reprint author), Ctr Dis Control & Prevent, Natl Ctr Zoonot Vector Borne & Enter Dis, Atlanta, GA 30329 USA. NR 6 TC 43 Z9 43 U1 5 U2 9 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0003-1488 J9 JAVMA-J AM VET MED A JI JAVMA-J. Am. Vet. Med. Assoc. PD JUL 15 PY 2008 VL 233 IS 2 BP 259 EP 261 DI 10.2460/javma.233.2.259 PG 3 WC Veterinary Sciences SC Veterinary Sciences GA 323LA UT WOS:000257446400027 PM 18627228 ER PT J AU Williams, JA Lumsden, JM Yu, X Feigenbamn, L Zhang, JJ Steinberg, SM Hodes, RJ AF Williams, Joy A. Lumsden, Joanne M. Yu, Xiang Feigenbamn, Lionel Zhang, Jingjing Steinberg, Seth M. Hodes, Richard J. TI Regulation of thymic NKT cell development by the B7-CD28 costimulatory pathway SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELLS; NEGATIVE SELECTION; CUTTING EDGE; CD28-DEFICIENT MICE; CORTICAL THYMOCYTES; POSITIVE SELECTION; CD28 COSTIMULATION; IN-VIVO; B-CELLS; HOMEOSTASIS AB Invariant NKT (iNKT) cells are a population of TCR alpha beta-expressing cells that are unique in several respects. In contrast to conventional T cells, iNKT cells are selected in the thymus for recognition of CD1, rather than conventional MHC class I or II, and are selected by CM-expressing double-positive thymocytes, rather than by the thymic stromal cells responsible for positive selection of conventional T cells. We have probed further the requirements for thymic iNKT cell development and find that these cells are highly sensitive to B7-CD28 costimulatory interactions, as evidenced by the substantially decreased numbers of thymic iNKT cells in CD28 and in B7 knockout mice. In contrast to the requirement for CD1, B7-CD28 signaling does not affect early iNKT cell lineage commitment, but exerts its influence on the subsequent intrathymic expansion and differentiation of iNKT cells. CD28 wild-type/CD28-deficient mixed bone marrow chimeras provided evidence of both cell-autonomous and non-cell-autonomous roles for CD28 during iNKT cell development. Paradoxically, transgenic mice in which thymic expression of B7 is elevated have essentially no measurable thymic iNKT cells. Taken together, these results demonstrate that the unique pathway involved in iNKT cell development is marked by a critical role of B7-CD28 interactions and that disruption or augmentation of this costimulatory interaction has substantial effects on iNKT cell development in the thymus. C1 [Williams, Joy A.; Zhang, Jingjing; Hodes, Richard J.] NCI, Expt Immunol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Natl Inst Hlth, Bethesda, MD 20892 USA. [Hodes, Richard J.] NIA, Natl Inst Hlth, Bethesda, MD 20892 USA. [Lumsden, Joanne M.] USN, US Mil Malaria Vaccine Program, Walter Reed Army Inst Med Res, Med Res Ctr, Silver Spring, MD 20910 USA. [Yu, Xiang] Superarray Biosci Corp, Frederick, MD 21704 USA. [Feigenbamn, Lionel] NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Frederick, MD 21702 USA. RP Hodes, RJ (reprint author), NCI, Expt Immunol Branch, Natl Inst Hlth, Bldg 10 Room 4B10,10 Ctr Dr, Bethesda, MD 20892 USA. EM HodesR@mail.nih.gov FU Intramural NIH HHS [Z01 BC009281-21] NR 54 TC 31 Z9 32 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 JUL 15 PY 2008 VL 181 IS 2 BP 907 EP 917 PG 11 WC Immunology SC Immunology GA 330QV UT WOS:000257958800009 PM 18606642 ER PT J AU Lunemann, JD Frey, O Eidner, T Baier, M Roberts, S Sashihara, J Volkmer, R Cohen, JI Hein, G Kamradt, T Munz, C AF Luenemann, Jan D. Frey, Oliver Eidner, Thorsten Baier, Michael Roberts, Susanne Sashihara, Junji Volkmer, Rudolf Cohen, Jeffrey I. Hein, Gert Kamradt, Thomas Muenz, Christian TI Increased frequency of EBV-specific effector memory CD8(+) T cells correlates with higher viral load in rheumatoid arthritis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; B-CELLS; MULTIPLE-SCLEROSIS; NUCLEAR ANTIGEN-1; PERIPHERAL-BLOOD; IN-VIVO; AUTOIMMUNE-DISEASES; SYNOVIAL TISSUE; INFECTION AB EBV is a candidate trigger of rheumatoid arthritis (RA). We determined both EBV-specific T cell and B cell responses and cell-associated EBV DNA copies in patients with RA and demographically matched healthy virus carriers. Patients with RA showed increased and broadened IgG responses to lytic and latent EBV-encoded Ags and 7-fold higher levels of EBV copy numbers in circulating blood cells. Additionally, patients with RA exhibited substantial expansions of CD8(+) T cells specific for pooled EBV Ags expressed during both B cell transformation and productive viral replication and the frequency of CD8(+) T cells specific for these Ags correlated with cellular EBV copy numbers. In contrast, CD4(+) T cell responses to EBV and T cell responses to human CMV Ags were unchanged, altogether arguing against a defective control of latent EBV infection in RA. Our data show that the regulation of EBV infection is perturbed in RA and suggest that increased EBV-specific effector T cell and Ab responses are driven by an elevated EBV load in RA. C1 [Luenemann, Jan D.; Roberts, Susanne; Muenz, Christian] Rockefeller Univ, Christopher H Browne Ctr Immunol & Immune Dis, Lab Viral Immunobiol, New York, NY 10021 USA. [Eidner, Thorsten; Hein, Gert] Univ Klinikum Jena, Innere Med Klin 3, Jena, Germany. [Baier, Michael] Univ Klinikum Jena, Inst Med Mikrobiol, Jena, Germany. NIAID, Lab Clin Infect Dis, Med Virol Sect, Bethesda, MD 20892 USA. [Frey, Oliver; Kamradt, Thomas] Univ Klinikum Jena, Inst Immunol, Jena, Germany. [Volkmer, Rudolf] Charite Univ Med Berlin, Inst Med Immunol, D-13353 Berlin, Germany. RP Munz, C (reprint author), Rockefeller Univ, Christopher H Browne Ctr Immunol & Immune Dis, Lab Viral Immunobiol, Box 390,1230 York Ave, New York, NY 10021 USA. EM munzc@rockefeller.edu RI Lunemann, Jan/G-8729-2011 OI Lunemann, Jan/0000-0002-3007-708X FU Intramural NIH HHS; NCI NIH HHS [R01 CA108609, R01CA101741, R01 CA108609-04A2, R01 CA101741, R01CA108609] NR 59 TC 27 Z9 28 U1 3 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 2008 VL 181 IS 2 BP 991 EP 1000 PG 10 WC Immunology SC Immunology GA 330QV UT WOS:000257958800017 PM 18606650 ER PT J AU Miyagawa, F Tagaya, Y Kim, BS Patel, HJ Ishida, K Ohteki, T Waldmann, TA Katz, SI AF Miyagawa, Fumi Tagaya, Yutaka Kim, Brian S. Patel, Hiral J. Ishida, Kazuto Ohteki, Toshiaki Waldmann, Thomas A. Katz, Stephen I. TI IL-15 serves as a costimulator in determining the activity of autoreactive CD8 T cells in an experimental mouse model of graft-versus-host-like disease SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RECEPTOR TRANSGENIC MICE; DENDRITIC CELLS; IN-VIVO; EFFECTOR FUNCTION; CLONAL ELIMINATION; CROSS-PRESENTATION; CUTTING EDGE; TOLERANCE; ANTIGEN; PROLIFERATION AB To elucidate the mechanisms controlling peripheral tolerance, we established two transgenic (Tg) mouse strains expressing different levels of membrane-bound OVA (mOVA) as a skin-associated self-Ag. When we transferred autoreactive TCR-Tg CD8 T cells (OT-I cells), keratin 14 (K14)-mOVA(high) Tg mice developed autoreactive skin disease (graft-vs-host disease (GVHD)-like skin lesions) while K14-mOVA(low) Tg mice did not. OT-I cells in K14-mOVA(high) Tg mice were fully activated with full development of effector function. In contrast, OT-1 cells in K14-mOVA(low) Tg mice proliferated but did not gain effector function. Exogenous IL-15 altered the functional status of OT-1 cells and concomitantly induced disease in K14-mOVA(low) Tg mice. Conversely, neutralization of endogenous IL-15 activity in K14-mOVA(high) Tg mice attenuated GVHD-like skin lesions induced by OT-1 cell transfer. Futhermore, K14-mOVA(high) Tg mice on IL-15 knockout or IL-15R alpha knockout backgrounds did not develop skin lesions after adoptive transfer of OT-I cells. These results identify IL-15 as an indispensable costimulator that can determine the functional fate of autoreactive CD8 T cells and whether immunity or tolerance ensues, and they suggest that inhibition of IL-15 function may be efficacious in blocking expression of autoimmunity where a breach in peripheral tolerance is suspected. C1 [Miyagawa, Fumi; Kim, Brian S.; Katz, Stephen I.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. [Tagaya, Yutaka; Patel, Hiral J.; Waldmann, Thomas A.] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. [Kim, Brian S.; Patel, Hiral J.] Howard Hughes Med Inst, NIH, Res Scholars Program, Bethesda, MD 20814 USA. [Ishida, Kazuto; Ohteki, Toshiaki] Akita Univ, Sch Med, Dept Immunol, Akita 010, Japan. RP Katz, SI (reprint author), NCI, Dermatol Branch, NIH, Bldg 31 Room 4C32, Bethesda, MD 20892 USA. EM katzs@od.niams.nih.gov FU Intramural NIH HHS [Z01 SC003657-33] NR 41 TC 12 Z9 12 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 2008 VL 181 IS 2 BP 1109 EP 1119 PG 11 WC Immunology SC Immunology GA 330QV UT WOS:000257958800030 PM 18606663 ER PT J AU Yu, CR Mahdi, RM Liu, XB Zhang, A Naka, T Kishimoto, T Egwuagu, CE AF Yu, Cheng-Rong Mahdi, Rashid M. Liu, Xuebin Zhang, Allen Naka, Tetsuji Kishimoto, Tadamitsu Egwuagu, Charles E. TI SOCS1 regulates CCR7 expression and migration of CD4(+) T cells into peripheral tissues SO JOURNAL OF IMMUNOLOGY LA English DT Article ID REACTIVE LYMPH-NODES; IFN-GAMMA; CYTOKINE SIGNALING-1; NEGATIVE REGULATION; UP-REGULATION; SUPPRESSOR; CHEMOKINE; INHIBITOR; EFFECTOR; PATHWAYS AB Suppressors of cytokine signaling (SOCS) proteins control many aspects of lymphocyte function through regulation of STAT pathways. SOCS1-deficient mice develop severe skin and eye diseases that result from massive infiltration of inflammatory cells into these tissues. In this study, we have used SOCS1-, STAT1-, or STAT6-deficient mice, as well as, T cells with stable overexpression or deletion of SOCS1, to examine whether SOCS1 is involved in regulating lymphocyte trafficking to peripheral tissues. We show that SOCS1 -deficient mice have increased numbers of T cells with characteristics of effector memory cells and expression of CCR7, a protein that promotes retention of T cells in lymphoid tissues, is markedly reduced in these cells. The decrease in CCR7 expression correlates with hyperactivation of STAT6, suggesting that aberrant recruitment of T cells into SOCS1-deficient mouse skin or eye results from abrogation of negative feedback regulation of STAT6 activation and CCR7 expression. Consistent with in vivo regulation of CCR7 expression and lymphocyte migration by SOCS1, forced overexpression of SOCS1 in T cells upregulates CCR7 expression and enhances chemotaxis toward CCL19 or CCL21. CCR6 and CXCR3 are also up-regulated on SOCS1-deficient T cells and in situ analysis of the cornea or retina further reveal that these cells may mediate the chronic skin and eye inflammation through recruitment of Th1 and Th17 cells into these tissues. Collectively, these results suggest that SOCS1 regulates steady-state levels of chemokine receptors through its inhibitory effects on STAT pathways and this may underscore its role in regulating recruitment and retention of effector cells into nonlymphoid tissues. C1 [Yu, Cheng-Rong; Mahdi, Rashid M.; Liu, Xuebin; Zhang, Allen; Egwuagu, Charles E.] NEI, Immunol Lab, Mol Immunol Sect, NIH, Bethesda, MD 20892 USA. [Naka, Tetsuji; Kishimoto, Tadamitsu] Osaka Univ, Grad Sch Frontier Biosci, Lab Immune Regulat, Osaka, Japan. RP Egwuagu, CE (reprint author), NEI, Immunol Lab, Mol Immunol Sect, NIH, Bldg 10,Room 10N116,10 Ctr Dr, Bethesda, MD 20892 USA. EM egwuaguc@nei.nih.gov RI Kishimoto, Tadamitsu/C-8470-2009 FU Intramural NIH HHS [Z01 EY000372-07] NR 34 TC 10 Z9 10 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 2008 VL 181 IS 2 BP 1190 EP 1198 PG 9 WC Immunology SC Immunology GA 330QV UT WOS:000257958800039 PM 18606672 ER PT J AU Malaspina, A Moir, S DiPoto, AC Ho, J Wang, W Roby, G O'Shea, MA Fauci, AS AF Malaspina, Angela Moir, Susan DiPoto, Angela C. Ho, Jason Wang, Wei Roby, Gregg O'Shea, Marie A. Fauci, Anthony S. TI CpG oligonucleotides enhance proliferative and effector responses of B cells in HIV-infected individuals SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNOSTIMULATORY PHOSPHOROTHIOATE OLIGONUCLEOTIDE; PLASMACYTOID DENDRITIC CELLS; TOLL-LIKE RECEPTORS; BACTERIAL-DNA; ANTIRETROVIRAL THERAPY; INFLUENZA VACCINATION; ACQUIRED-IMMUNITY; ANTIBODY-RESPONSE; MEMORY; ACTIVATION AB Stimulation through TLR represents a new therapeutic approach for enhancing Ab responses to vaccination. Considering that Ab responses are decreased in HIV disease and that B cells express TLR9 and respond to TLR9 agonists, we investigated the responsiveness of B cell subpopulations from HIV-infected and uninfected individuals to the TLR9 agonist CpG oligonucleotide type B (CpG-B) in the presence and absence of BCR ligation and T cell help (CD40L). CpG-B was equally effective in stimulating the proliferation of naive B cells of HIV-infected individuals and HIV-negative individuals, and, when combined with BCR and CD40 ligation, cytokine secretion by naive B cells was also comparable in HIV-infected and uninfected individuals. In contrast, CD27(+) memory/activated B cells of HIV-infected individuals with active disease were less responsive to CpG-B in terms of proliferation and cytokine secretion when compared with CD27' B cells of HIV-negative and HIV-infected individuals whose viremia was controlled by antiretroviral therapy. These findings suggest that despite abnormalities in memory B cells of HIV-infected individuals with active disease, naive B cells of HIV-infected individuals, irrespective of disease status, can respond to TLR9 agonists and that the incorporation of such agents in vaccine formulations may enhance their Ab responses to vaccination. C1 [Malaspina, Angela; Moir, Susan; DiPoto, Angela C.; Ho, Jason; Wang, Wei; Roby, Gregg; O'Shea, Marie A.; Fauci, Anthony S.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Malaspina, A (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Room 6A11,10 Ctr Dr, Bethesda, MD 20892 USA. EM amalaspina@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000825-10] NR 48 TC 31 Z9 32 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 JUL 15 PY 2008 VL 181 IS 2 BP 1199 EP 1206 PG 8 WC Immunology SC Immunology GA 330QV UT WOS:000257958800040 PM 18606673 ER PT J AU McKarns, SC Schwartz, RH AF McKarns, Susan C. Schwartz, Ronald H. TI Biphasic regulation of Il2 transcription in CD4(+) T cells: Roles for TNF-alpha receptor signaling and chromatin structure SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERLEUKIN-2 GENE-TRANSCRIPTION; IL-2 GENE; IN-VIVO; C-REL; LYMPHOCYTE ACTIVATION; AUTOIMMUNE-DISEASE; PROMOTER REGION; EXPRESSION; CD28; MICE AB We describe a novel biphasic regulation of Il2 transcription in naive CD4(+) T cells. Few (similar to 5%) CD4(+) T cells transcribe 112 within 6 h of anti-TCR-beta plus anti-CD28 stimulation (early phase). Most naive CD4(+) T cells do not initiate 112 transcription until after an additional similar to 12 h of T cell stimulation Oate phase). In comparison, essentially all previously activated (Pre-Ac) CD4(+) T cells that transcribe 112 do so with an early-phase response. Late-phase 112 expression mostly requires c-Rel, CD28, and TNFR signaling. In contrast, early-phase transcription is only partly c-Rel and CD28 dependent and TNFR independent. There was also increased stable DNA accessibility at the 112 locus and elevated c-Rel expression in resting Pre-Ac CD4(+) cells. Upon T cell activation, a faster and greater increase in DNA accessibility as well as c-Rel nuclear expression were observed in Pre-Ac CD4(+) cells relative to naive CD4(+) T cells. In addition, both acetylated histone H3 and total H3 decreased at the 112 locus upon rechallenge of Pre-Ac CD4(+) T cells, whereas increased acetylated histone H3 with no change in total H3 was observed following activation of naive CD4(+) T cells. We propose a model in which nucleosome disassembly facilitates rapid initiation of 112 transcription in CD4(+) T cells, and suggest that a threshold level of c-Rel must be reached for 112 promoter activity in both naive and Pre-Ac CD4(+) T cells. This is provided, at least partially, by TNFR signaling during priming, but not during recall. C1 [McKarns, Susan C.] Univ Missouri, Sch Med, Ctr Cellular & Mol Immunol, Hugh E Stephenson Jr Dept Surg, Columbia, MO 65212 USA. [McKarns, Susan C.] Univ Missouri, Sch Med, Ctr Cellular & Mol Immunol, Dept Mol Microbiol & Immunol, Columbia, MO 65212 USA. [McKarns, Susan C.; Schwartz, Ronald H.] NIAID, Lab Cellular & Mol Immunol, NIH, Bethesda, MD 20892 USA. RP McKarns, SC (reprint author), Univ Missouri, Columbia Sch Med, Ctr Cellular & Mol Immunol, Dept Surg, M616 Med Sci Bldg,1 Hosp Dr, Columbia, MO 65212 USA. EM mckarnss@health.missouri.edu FU Intramural NIH HHS [Z01 AI000994-01] NR 71 TC 18 Z9 18 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 JUL 15 PY 2008 VL 181 IS 2 BP 1272 EP 1281 PG 10 WC Immunology SC Immunology GA 330QV UT WOS:000257958800048 PM 18606681 ER PT J AU Longo, NS Satorius, CL Plebani, A Durandy, A Lipsky, PE AF Longo, Nancy S. Satorius, Colleen L. Plebani, Alessandro Durandy, Anne Lipsky, Peter E. TI Characterization of Ig gene somatic hypermutation in the absence of activation-induced cytidine deaminase SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DNA-POLYMERASE-ETA; IMMUNOGLOBULIN SWITCH REGIONS; B-CELLS; REPLICATION FIDELITY; SELECTIVE INFLUENCES; ANTIBODY GENES; MUTATIONS; REPERTOIRE; AID; RECOMBINATION AB Somatic hypermutation (SHM) of Ig genes depends upon the deamination of C nucleotides in WR (C) under barY (W = A/T, R = A/G, Y = C/T) motifs by activation-induced cytidine deaminase (AICDA). Despite this, a large number of mutations occur in WA motifs that can be accounted for by the activity of polymerase eta (POL eta). To determine whether there are AICDA-independent mutations and to characterize the relationship between AICDA- and POL eta-mediated mutations, 1470 H chain and 1313 kappa- and lambda-chain rearrangements from three AICDA(-/-) patients were analyzed. The Ig mutation frequency of all V-H genes from AICDA(-/-) patients was 40-fold less than that of normal donors, whereas the mutation frequency of mutated V-H sequences from AICDA(-/-) patients was 6.8-fold less than that of normal donors. AICDA(-/-) B cells lack mutations in WRCY/RGYW motifs as well as replacement mutations and mutational targeting in complementarity-determining regions. A significantly reduced mutation frequency in WA motifs compared with normal donors and an increased percentage of transitions, which may relate to reduced uracil DNA-glycosylase activity, suggest a role for AICDA in regulating POL eta and uracil DNA-glycosylase activity. Similar results were observed in V-L rearrangements. The residual mutations were predominantly G:C substitutions, indicating that AICDA-independent cytidine deamination was a likely, yet inefficient, mechanism for mutating Ig genes. C1 [Longo, Nancy S.; Satorius, Colleen L.; Lipsky, Peter E.] NIAMSD, Autoimmun Branch, Bethesda, MD 20892 USA. [Plebani, Alessandro] Univ Brescia, Pediat Clin, Brescia, Italy. [Plebani, Alessandro] Univ Brescia, Ist Med Mol Angelo Nocivelli, Brescia, Italy. [Durandy, Anne] INSERM, U768, Paris, France. [Durandy, Anne] Univ Paris 05, Fac Med Rene Descartes, Paris, France. [Durandy, Anne] Hop Necker Enfants Malad, AP HP, Serv Immunol & Haematol Pediat, Paris, France. RP Lipsky, PE (reprint author), NIAMSD, Autoimmun Branch, 9000 Rockville Pike,Bldg 10,6D47C, Bethesda, MD 20892 USA. EM lipskyp@mail.nih.gov RI Plebani, Alessandro/C-8593-2011 FU Intramural NIH HHS [Z99 AI999999] NR 41 TC 12 Z9 12 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 2008 VL 181 IS 2 BP 1299 EP 1306 PG 8 WC Immunology SC Immunology GA 330QV UT WOS:000257958800051 PM 18606684 ER PT J AU Southgate, EL He, RL Gao, JL Murphy, PM Nanamori, M Ye, RD AF Southgate, Erica L. He, Rong L. Gao, Ji-Liang Murphy, Philip M. Nanamori, Masakatsu Ye, Richard D. TI Identification of formyl peptides from Listeria monocytogenes and Staphylococcus aureus as potent chemoattractants for mouse neutrophils SO JOURNAL OF IMMUNOLOGY LA English DT Article ID N-FORMYLPEPTIDE RECEPTOR; METHIONYL-LEUCYL-PHENYLALANINE; PROTEIN-COUPLED RECEPTORS; HIGH CHEMOTACTIC POTENCY; LIGAND-BINDING; TYROSINE PHOSPHORYLATION; ESCHERICHIA-COLI; DENDRITIC CELLS; HOST-DEFENSE; ADP-RIBOSE AB The prototypic formyl peptide N-formyl-Met-Leu-Phe (fMLF) is a major chemoattractant found in Escherichia coli culture supernatants and a potent agonist at human formyl peptide receptor (FPR) 1. Consistent with this, fMLF induces bactericidal functions in human neutrophils at nanomolar concentrations. However, it is a much less potent agonist for mouse FPR (mFPR) 1 and mouse neutrophils, requiring micromolar concentrations for cell activation. To determine whether other bacteria produce more potent agonists for mFPR1, we examined formyl peptides from Listeria monocytogenes and Staphylococcus aureus for their abilities to activate mouse neutrophils. A pentapeptide (N-formyl-Met-Ile-Val-Ile-Leu (fMIVIL)) from L monocytogenes and a tetrapeptide (N-formyl-Met-Ile-Phe-Leu (fMIFL)) from S. aureus were found to induce mouse neutrophil chemotaxis at 1-10 nM and superoxide production at 10-100 nM, similar to the potency of fMLF on human neutrophils. Using transfected cell lines expressing mFPR1 and mFPR2, which are major forms of FPRs in mouse neutrophils, we found that mFPR1 is responsible for the high potency of fMIVIL and fMIFL. In comparison, activation of mFPR2 requires micromolar concentrations of the two peptides. Genetic deletion of mfpr1 resulted in abrogation of neutrophil superoxide production and degranulation in response to fMIVIL and fMIFL, further demonstrating that mFPR1 is the primary receptor for detection of these formyl peptides. In conclusion, the formyl peptides from L. monocytogenes and S. aureus are similar to 100-fold more potent than fMLF in activating mouse neutrophils. The ability of mFPR1 to detect bacterially derived formyl peptides indicates that this important host defense mechanism is conserved in mice. C1 [Southgate, Erica L.; He, Rong L.; Nanamori, Masakatsu; Ye, Richard D.] Univ Illinois, Dept Pharmacol, Coll Med, Chicago, IL 60612 USA. [Gao, Ji-Liang; Murphy, Philip M.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Ye, RD (reprint author), Univ Illinois, Dept Pharmacol, Coll Med, 835 S Wolcott Ave, Chicago, IL 60612 USA. EM yer@uic.edu RI Ye, Richard/O-5223-2016 OI Ye, Richard/0000-0002-2164-5620 FU NHLBI NIH HHS [HL077806, P01 HL077806, P01 HL077806-030002, T32 HL007829, T32 HL007829-14]; NIAID NIH HHS [AI033503, AI040176, R01 AI033503, R01 AI033503-14, R01 AI040176, R01 AI040176-10, R56 AI033503, R56 AI040176] NR 54 TC 43 Z9 45 U1 3 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 2008 VL 181 IS 2 BP 1429 EP 1437 PG 9 WC Immunology SC Immunology GA 330QV UT WOS:000257958800064 PM 18606697 ER PT J AU Wolf, R Howard, OMZ Dong, HF Voscopoulos, C Boeshans, K Winston, J Divi, R Gunsior, M Goldsmith, P Ahvazi, B Chavakis, T Oppenheim, JJ Yuspa, SH AF Wolf, Ronald Howard, O. M. Zack Dong, Hui-Fang Voscopoulos, Christopher Boeshans, Karen Winston, Jason Divi, Rao Gunsior, Michele Goldsmith, Paul Ahvazi, Bijan Chavakis, Triantafyllos Oppenheim, Joost J. Yuspa, Stuart H. TI Chemotactic activity of S100A7 (psoriasin) is mediated by the receptor for advanced glycation end products and potentiates inflammation with highly homologous but functionally distinct S100A15 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GENE-EXPRESSION; HUMAN SKIN; MOLECULAR-CLONING; PROTEIN PSORIASIN; CELL RECRUITMENT; MESSENGER-RNA; RAGE; DIFFERENTIATION; PATTERN; IMMUNE AB Human S100 A7 (psoriasin) is overexpressed in inflammatory diseases. The recently discovered, co-evolved hS100A15 is almost identical in sequence and up-regulated with hS100A7 during cutaneous inflammation. The functional role of these closely related proteins for inflammation remains undefined. By generating specific Abs, we demonstrate that hS100A7 and hS100A15 proteins are differentially expressed by specific cell types in the skin. Although highly homologous, both proteins are chemoattractants with distinct chemotactic activity for leukocyte subsets. We define RAGE (receptor for advanced glycation end products) as the hS100A7 receptor, whereas hS100A15 functions through a Gi protein-coupled receptor. hS100A7-RAGE binding, signaling, and chemotaxis are zinc-dependent in vitro, reflecting the previously reported zinc-mediated changes in the hS100A7 dimer structure. When combined, hS100A7 and hS100A15 potentiate inflammation in vivo. Thus, proinflammatory synergism in disease may be driven by the diverse biology of these almost identical proteins that have just recently evolved. The identified S100A7 interaction with RAGE may provide a novel therapeutic target for inflammation. C1 [Wolf, Ronald; Voscopoulos, Christopher; Winston, Jason; Divi, Rao; Yuspa, Stuart H.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Chavakis, Triantafyllos] NCI, Ctr Canc Res, Expt Immunol Branch, Bethesda, MD 20892 USA. [Gunsior, Michele; Goldsmith, Paul] NCI, Ctr Canc Res, Antibody & Prot Purificat Unit, Bethesda, MD 20892 USA. [Dong, Hui-Fang] NCI, Sci Applicat Int Corp Frederick, Div Basic Sci & Cellular Immunol, Frederick, MD 21702 USA. [Boeshans, Karen; Ahvazi, Bijan] NIAMSD, Xray Crystallog Facil, NIH, Bethesda, MD 20892 USA. RP Yuspa, SH (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, 37 Convent Dr,MSC-4255,Bldg 37,Room 4068A, Bethesda, MD 20892 USA. EM yuspas@mail.nih.gov RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 FU Intramural NIH HHS [Z99 CA999999] NR 50 TC 90 Z9 92 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 2008 VL 181 IS 2 BP 1499 EP 1506 PG 8 WC Immunology SC Immunology GA 330QV UT WOS:000257958800072 PM 18606705 ER PT J AU Lamaris, GA Lewis, RE Chamilos, G May, GS Safdar, A Walsh, TJ Raad, II Kontoyiannis, DP AF Lamaris, Gregory A. Lewis, Russell E. Chamilos, Georgios May, Gregory S. Safdar, Amar Walsh, Thomas J. Raad, Issam I. Kontoyiannis, Dimitrios P. TI Caspofungin-mediated beta-glucan unmasking and enhancement of human polymorphonuclear neutrophil activity against Aspergillus and non-Aspergillus hyphae SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 47th Interscience Conference on Antimicrobial Agents and Chemotherapy CY SEP 17-20, 2007 CL Chicago, IL ID ANTIFUNGAL ACTIVITY; IMMUNE RECOGNITION; FUNGAL-INFECTIONS; IN-VITRO; DECTIN-1; ECHINOCANDIN; FUMIGATUS; SYNTHASE; RECEPTOR; MACROPHAGES AB Background. We investigated whether caspofungin and other echinocandins have immune-enhancing properties that influence human polymorphonuclear neutrophil (PMN)-mediated mold hyphal damage. Materials and methods. Using aniline blue staining, we compared patterns of beta-glucan exposure in Aspergillus fumigatus, Aspergillus terreus, Rhizopus oryzae, Fusarium solani, Fusarium oxysporum, Scedosporium prolificans, and Scedosporium apiospermum hyphae after caspofungin exposure. We also determined PMN-mediated hyphal damage occurring with or without preexposure to caspofungin or with preexposure to the combination of caspofungin and anti-beta-glucan monoclonal antibody, using 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-sH-tetrazolium hydroxide (XTT) assay. Results. Preincubation with caspofungin ( 32 mu g/mL for R. oryzae; 0.0625 mu g/mL for other isolates) increased exposure to beta-glucan. PMN-induced damage increased after caspofungin exposure and was further augmented by the addition of anti-beta-glucan antibody. Preincubation with micafungin or anidulafungin had similar effects on PMN-induced damage of A. fumigatus hyphae. Finally, preexposure of A. fumigatus, but not S. prolificans, to caspofungin induced expression of Dectin-1 by PMN. Conclusions. The results of the present study suggest inducement of beta-glucan unmasking by echinocandins and enhancement of PMN activity against mold hyphae, thereby supporting the immunopharmacologic mode of action of echinocandins. C1 [Lamaris, Gregory A.; Lewis, Russell E.; Chamilos, Georgios; Safdar, Amar; Raad, Issam I.; Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Dept Infect Dis, Houston, TX 77030 USA. [Lamaris, Gregory A.; Lewis, Russell E.; Chamilos, Georgios; Safdar, Amar; Raad, Issam I.; Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Dept Infect Control, Houston, TX 77030 USA. [Lamaris, Gregory A.; Lewis, Russell E.; Chamilos, Georgios; Safdar, Amar; Raad, Issam I.; Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Dept Employee Hlth, Houston, TX 77030 USA. [May, Gregory S.] Univ Texas MD Anderson Canc Ctr, Lab Med, Houston, TX 77030 USA. [Lewis, Russell E.; Kontoyiannis, Dimitrios P.] Univ Houston, Coll Pharm, Houston, TX 77030 USA. [Walsh, Thomas J.] NCI, Pediatr Oncol Branch, Immunocompromised Host Sect, Bethesda, MD USA. RP Lamaris, GA (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Infect Dis, Houston, TX 77030 USA. NR 37 TC 103 Z9 106 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD JUL 15 PY 2008 VL 198 IS 2 BP 186 EP 192 DI 10.1086/589305 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 321QA UT WOS:000257320400006 PM 18500936 ER PT J AU Mizukoshi, E Eisenbach, C Edlin, BR Newton, KP Raghuraman, S Weiler-Normann, C Tobler, LH Busch, MP Carrington, M McKeating, JA O'Brien, TR Rehermann, B AF Mizukoshi, Eishiro Eisenbach, Christoph Edlin, Brian R. Newton, Kimberly P. Raghuraman, Sukanya Weiler-Normann, Christina Tobler, Leslie H. Busch, Michael P. Carrington, Mary McKeating, Jane A. O'Brien, Thomas R. Rehermann, Barbara TI Hepatitis C virus (HCV)-specific immune responses of long-term injection drug users frequently exposed to HCV SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID T-CELL RESPONSES; SINGLE-SOURCE OUTBREAK; NEUTRALIZING ANTIBODY; SAN-FRANCISCO; VIRAL CLEARANCE; B-VIRUS; INFECTION; HIV; PROSTITUTES; PREVALENCE AB Background. Injection drug users (IDUs) who successfully clear hepatitis C virus (HCV) have a reduced risk of developing chronic reinfection, despite their continuing exposure to the virus. To identify immunological correlates for this apparent protection, we studied HCV-specific immune responses in long-term IDUs (duration, > 10 years). Methods. HCV-specific T cell responses were assessed in proliferation, enzyme-linked immunospot (ELISPOT), interferon (IFN)-gamma secretion, and cytotoxicity assays, whereas HCV-specific antibodies were assessed in enzyme immunoassays (EIAs), chemiluminescent assays, and in vitro neutralization assays. Results. HCV-specific T cell proliferation and IFN-gamma production were more common in nonviremic EIA-positive IDUs (16[94%] of 17 IDUs) than in viremic EIA-positive IDUs (9[45%] of 20 IDUs) (P = .003). They were also noted in 16 (62%) of 26 nonviremic EIA-negative IDUs. In contrast, 19 (90%) of 21 viremic IDUs displayed neutralizing antibodies (nAbs), compared with 9 (56%) of 16 nonviremic EIA-positive IDUs ( P = .04) and 0 of 24 nonviremic EIA-negative IDUs. Nonviremic IDUs with nAbs were older ( P = .0115) than those without nAbs, but these groups did not differ in terms of either injection drug use duration or HCV-specific T cell responses. Conclusion. The reduced risk of HCV persistence in IDUs previously recovered from HCV infection correlated with T cell responses, and prolonged antigenic stimulation appears to be required to maintain humoral responses. C1 [Mizukoshi, Eishiro; Eisenbach, Christoph; Raghuraman, Sukanya; Weiler-Normann, Christina; Rehermann, Barbara] NIDDK, Liver Dis Branch, Immunol Sect, Bethesda, MD 20892 USA. [O'Brien, Thomas R.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Carrington, Mary] NCI, Lab Genom Divers Sci Applicat Int Cooperat Freder, Frederick, MD USA. [Edlin, Brian R.; Busch, Michael P.] Univ Calif San Francisco, San Francisco, CA USA. [Tobler, Leslie H.; Busch, Michael P.] Blood Syst Res Inst, San Francisco, CA USA. [Edlin, Brian R.] Cornell Univ, Weill Med Coll, Ctr Study Hepatitis C, Ithaca, NY 14853 USA. [Newton, Kimberly P.; McKeating, Jane A.] Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10021 USA. RP Mizukoshi, E (reprint author), NIDDK, Liver Dis Branch, Immunol Sect, Bethesda, MD 20892 USA. OI Edlin, Brian/0000-0001-8172-8797; McKeating, Jane/0000-0002-7229-5886 FU Intramural NIH HHS; Medical Research Council [G0400802, G0801976]; NCI NIH HHS [N01 CO012400, N01-CO-12400, N01CO12400]; NIAID NIH HHS [AI050798, R01 AI050798]; NIDA NIH HHS [R01 DA009532, R01 DA013245, R01 DA016159, R01-DA09532, R01-DA13245, R01-DA16159] NR 47 TC 42 Z9 43 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUL 15 PY 2008 VL 198 IS 2 BP 203 EP 212 DI 10.1086/589510 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 321QA UT WOS:000257320400008 PM 18505381 ER PT J AU Vuong, C Kocianova, S Yu, J Kadurugamuwa, JL Otto, M AF Vuong, Cuong Kocianova, Stanislava Yu, Jun Kadurugamuwa, Jagath L. Otto, Michael TI Development of real-time in vivo imaging of device-related Staphylococcus epidermidis infection in mice and influence of animal immune status on susceptibility to infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID BIOFILM FORMATION; MOUSE MODEL; VIRULENCE AB Staphylococcus epidermidis is the leading cause of hospital-acquired device-related infections, but there is a lack of suitable methods to investigate the pathogenesis of S. epidermidis infection. We created a bioluminescent strain of S. epidermidis and developed a subcutaneous catheter-related murine infection model for real-time monitoring of biofilm-associated infection. Additionally, we compared severely immunocompromised and immunocompetent mice, demonstrating the substantial effect of animal immune status on susceptibility to experimentally induced S. epidermidis disease. This study presents a novel approach for investigating the in vivo details of the pathogenesis of S. epidermidis infection. C1 [Vuong, Cuong] Univ Massachusetts, Sch Med, Dept Anesthesiol, Worcester, MA 01655 USA. [Vuong, Cuong] Univ Massachusetts, Sch Med, Dept Mol Genet & Microbiol, Worcester, MA 01655 USA. [Yu, Jun; Kadurugamuwa, Jagath L.] Xenogen, Alameda, CA USA. [Vuong, Cuong; Kocianova, Stanislava; Otto, Michael] NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT USA. RP Vuong, C (reprint author), Univ Massachusetts, Sch Med, Dept Anesthesiol, 55 Lake Ave N,S2-717, Worcester, MA 01655 USA. EM cuong.vuong@umassmed.eduM; motto@niaid.nih.gov OI Otto, Michael/0000-0002-2222-4115 FU Intramural NIH HHS [Z01 AI000904-06] NR 15 TC 22 Z9 22 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUL 15 PY 2008 VL 198 IS 2 BP 258 EP 261 DI 10.1086/589307 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 321QA UT WOS:000257320400015 PM 18491976 ER PT J AU Andreasen, V Viboud, C Simonsen, L AF Andreasen, Viggo Viboud, Cecile Simonsen, Lone TI Influenza pandemics, immune cross-reactivity, and pandemic control strategies - Reply SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter C1 [Andreasen, Viggo] Roskilde Univ Ctr, Dept Sci, DK-4000 Roskilde, Denmark. [Viboud, Cecile] Fogarty Int Ctr, NIH, Bethesda, MD USA. [Simonsen, Lone] George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC USA. RP Andreasen, V (reprint author), Roskilde Univ Ctr, Dept Sci, Bldg 27-1, DK-4000 Roskilde, Denmark. EM viggo@ruc.dk NR 10 TC 0 Z9 0 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUL 15 PY 2008 VL 198 IS 2 BP 295 EP 296 DI 10.1086/589303 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 321QA UT WOS:000257320400022 ER PT J AU Butts, C Candando, K Johnson, A Kang, Z Marques, A Silverman, M Tait, A Sternberg, EM AF Butts, C. Candando, K. Johnson, A. Kang, Z. Marques, A. Silverman, M. Tait, A. Sternberg, E. M. TI Neuroendocrine regulation of immunity: Role in susceptibility to autoimmune, inflammatory and infectious diseases SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT International Neuroimmunology Symposium CY MAR 13-14, 2008 CL Univ Coll Dublin, Dublin, IRELAND HO Univ Coll Dublin C1 [Butts, C.; Candando, K.; Johnson, A.; Kang, Z.; Marques, A.; Silverman, M.; Tait, A.; Sternberg, E. M.] NIMH, NIH, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD JUL 15 PY 2008 VL 197 IS 2 BP 160 EP 160 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 336TY UT WOS:000258388700014 ER PT J AU Xu, S Yang, J Shen, J AF Xu, Su Yang, Jehoon Shen, Jun TI Measuring N-acetylaspartate synthesis in vivo using proton magnetic resonance spectroscopy SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE N-acetylaspartate synthesis; proton magnetic resonance spectroscopy; in vivo ID ACETYL-L-ASPARTATE; RAT-BRAIN; PULSE SEQUENCE; NERVOUS-SYSTEM; ACETYLASPARTYLGLUTAMATE; ASPARTOACYLASE; GLUTAMATE; NMR; LOCALIZATION; METABOLISM AB N-Acetylaspartate (NAA) is an important marker of neuronal function and viability that can be measured using magnetic resonance spectroscopy (MRS). In this paper, we proposed a method to measure NAA synthesis using proton MRS with infusion of uniformly (13)C-labeled glucose, and demonstrated its feasibility in an in vivo study of the rat brain. The rate of (13)C-label incorporation into the acetyl group of NAA was measured using a localized, long echo-time proton MRS method. Signals from the (13)C satellites of the main NAA methyl protons at 2.02 ppm were continuously monitored for 10 h. Quantification of the data based on a linear kinetic model showed that NAA synthesis rate in isoflurane-anesthetized rats was 0.19 +/- 0.02 mu mol/g/h (mean +/- standard deviation, n = 12). Published by Elsevier B.V. C1 [Shen, Jun] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. RP Xu, S (reprint author), NIMH, Mol Imaging Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM suxu@intra.nimh.nih.gov; yangj@intra.nimh.nih.gov; shenj@intra.nimh.nih.gov FU Intramural NIH HHS [NIH0011550095, Z01 MH002803-05] NR 37 TC 7 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD JUL 15 PY 2008 VL 172 IS 1 BP 8 EP 12 DI 10.1016/j.jneumeth.2008.04.001 PG 5 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 323YX UT WOS:000257485800002 PM 18486230 ER PT J AU Zou, QH Zhu, CZ Yang, YH Zuo, XN Long, XY Cao, QJ Wang, YF Zang, YF AF Zou, Qi-Hong Zhu, Chao-Zhe Yang, Yihong Zuo, Xi-Nian Long, Xiang-Yu Cao, Qing-Jiu Wang, Yu-Feng Zang, Yu-Feng TI An improved approach to detection of amplitude of low-frequency fluctuation (ALFF) for resting-state fMRI: Fractional ALFF SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE functional magnetic resonance imaging; resting state; amplitude of low-frequency fluctuation (ALFF); spontaneous brain activity ID FUNCTIONAL MAGNETIC-RESONANCE; DEFICIT HYPERACTIVITY DISORDER; BOLD SIGNAL FLUCTUATIONS; DEFAULT-MODE NETWORK; ALZHEIMERS-DISEASE; BRAIN-FUNCTION; MOTOR CORTEX; BASE-LINE; CONNECTIVITY; MRI AB Most of the resting-state functional magnetic resonance imaging (fMRI) studies demonstrated the correlations between spatially distinct brain areas from the perspective of functional connectivity or functional integration. The functional connectivity approaches do not directly provide information of the amplitude of brain activity of each brain region within a network. Alternatively, an index named amplitude of low-frequency fluctuation (ALFF) of the resting-state fMRI signal has been suggested to reflect the intensity of regional spontaneous brain activity. However, it has been indicated that the ALFF is also sensitive to the physiological noise. The current study proposed a fractional ALFF (fALFF) approach, i.e., the ratio of power spectrum of low-frequency (0.01-0.08 Hz) to that of the entire frequency range and this approach was tested in two groups of resting-state fMRI data. The results showed that the brain areas within the default mode network including posterior cingulate cortex, precuneus, medial prefrontal cortex and bilateral inferior parietal lobule had significantly higher fALFF than the other brain areas. This pattern was consistent with previous neuroimaging results. The non-specific signal components in the cistern areas in resting-state fMRI were significantly suppressed, indicating that the fALFF approach improved the sensitivity and specificity in detecting spontaneous brain activities. Its mechanism and sensitivity to abnormal brain activity should be evaluated in the future studies. (C) 2008 Elsevier B.V. All rights reserved. C1 [Zou, Qi-Hong; Zhu, Chao-Zhe; Long, Xiang-Yu; Zang, Yu-Feng] Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China. [Yang, Yihong] Natl Inst Drug Abuse, Neuroimaging Res Branch, NIH, Baltimore, MD 21042 USA. [Zuo, Xi-Nian; Long, Xiang-Yu] Chinese Acad Sci, Inst Automat, Natl Lab Pattern Recognit, Beijing 100864, Peoples R China. [Cao, Qing-Jiu; Wang, Yu-Feng] Peking Univ, Inst Mental Hlth, Beijing 100871, Peoples R China. [Zang, Yu-Feng] Anding Hosp, Beijing, Peoples R China. [Zang, Yu-Feng] Capital Med Univ, Dept Psychiat, Beijing, Peoples R China. RP Zang, YF (reprint author), Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China. EM zangyf@263.net RI Zuo, Xi-Nian/A-7273-2009; ZANG, Yu-Feng/J-1558-2012; OI ZANG, Yu-Feng/0000-0003-1833-8010; Zuo, Xi-Nian/0000-0001-9110-585X FU Intramural NIH HHS [Z01 DA000469-04, Z01 DA000469-05, Z99 DA999999] NR 36 TC 311 Z9 354 U1 7 U2 40 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD JUL 15 PY 2008 VL 172 IS 1 BP 137 EP 141 DI 10.1016/j.jneumeth.2008.04.012 PG 5 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 323YX UT WOS:000257485800020 PM 18501969 ER PT J AU Guerreiro, RJ Santana, I Bras, JM Revesz, T Rebelo, O Ribeiro, MH Santiago, B Oliveira, CR Singleton, A Hardy, J AF Guerreiro, Rita Joao Santana, Isabel Bras, Jose Miguel Revesz, Tamas Rebelo, Olinda Ribeiro, Maria Helena Santiago, Beatriz Oliveira, Catarina Resende Singleton, Andrew Hardy, John TI Novel progranulin mutation: Screening for PGRN mutations in a Portuguese series of FTD/CBS cases SO MOVEMENT DISORDERS LA English DT Article DE progranulin; frontotemporal dementia; corticobasal syndrome; Portuguese population ID FRONTOTEMPORAL LOBAR DEGENERATION; UBIQUITIN-POSITIVE INCLUSIONS; DEMENTIA; GENE; IMMUNOHISTOCHEMISTRY; HETEROGENEITY; PATHOLOGY; CRITERIA AB Mutations in the progranulin (PGRN) gene were recently described as the cause of ubiquitin positive frontotemporal dementia (FFD) in many families. Different frequencies of these genetic changes have been reported in diverse populations leading us to determine if these mutations were a major cause of FFD in the Portuguese population. The entire coding sequence plus exon 0 of PGRN were sequenced in a consecutive series of 46 FTD/CBS Portuguese patients. Two mutations were found: a novel pathogenic insertion (p.Gln300GlnfsX61) and a previously described point variant (p.T182M) of unclear pathogenicity. Pathogenic mutations in the PGRN gene were found in one of the 36 probands studied (3% of the probands in our series) who had a corticobasal syndrome presentation, indicating that in the Portuguese population, mutations in this gene are not a major cause of FFD. (C) 2008 Movement Disorder Society. C1 [Guerreiro, Rita Joao; Bras, Jose Miguel; Singleton, Andrew; Hardy, John] NIA, NIH, Neurogenet Lab, Porter Neurosci Ctr, Bethesda, MD 20852 USA. [Guerreiro, Rita Joao; Bras, Jose Miguel; Ribeiro, Maria Helena; Oliveira, Catarina Resende] Univ Coimbra, Ctr Neurosci & Cell Biol, Coimbra, Portugal. [Santana, Isabel; Rebelo, Olinda; Santiago, Beatriz; Oliveira, Catarina Resende] Univ Coimbra, Neurol Serv, Coimbra, Portugal. [Revesz, Tamas; Hardy, John] UCL, Inst Neurol, Queen Sq Brain Bank, Dept Mol Neurosci, London, England. RP Guerreiro, RJ (reprint author), NIA, NIH, Neurogenet Lab, Porter Neurosci Ctr, Room 1A-1010,35 Convent Rd, Bethesda, MD 20852 USA. EM portalegrer@nia.nih.gov RI Singleton, Andrew/C-3010-2009; Bras, Jose/D-3366-2009; Oliveira, Catarina/F-3685-2010; Hardy, John/C-2451-2009; Guerreiro, Rita/A-1327-2011; Bras, Jose/A-1428-2011; Revesz, Tamas/A-8732-2010; OI Revesz, Tamas/0000-0003-2501-0259; Oliveira, Catarina/0000-0001-6942-4328; Santana, Isabel/0000-0002-8114-9434 FU Intramural NIH HHS; Medical Research Council [G0701075] NR 23 TC 22 Z9 23 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JUL 15 PY 2008 VL 23 IS 9 BP 1269 EP 1273 DI 10.1002/mds.22078 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 337FV UT WOS:000258421800011 PM 18464284 ER PT J AU Voon, V AF Voon, Valerie TI Reward II SO MOVEMENT DISORDERS LA English DT Meeting Abstract CT 1st International Meeting on Impulse Control Disorders in Parkinsons Disease CY JUL 12-13, 2007 CL Toronto, CANADA C1 [Voon, Valerie] NINDS, NIH, Human Motor Control Sect, Bethesda, MD 20892 USA. EM voonv@ninds.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JUL 15 PY 2008 VL 23 IS 9 BP 1336 EP 1336 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 337FV UT WOS:000258421800041 ER PT J AU Galpern, WR AF Galpern, Wendy R. TI Treatment approaches for impulse control disorders in Parkinson's disease SO MOVEMENT DISORDERS LA English DT Meeting Abstract CT 1st International Meeting on Impulse Control Disorders in Parkinsons Disease CY JUL 12-13, 2007 CL Toronto, CANADA C1 [Galpern, Wendy R.] NINDS, NIH, Bethesda, MD 20892 USA. EM galpernw@ninds.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JUL 15 PY 2008 VL 23 IS 9 BP 1342 EP 1343 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 337FV UT WOS:000258421800052 ER PT J AU Davatzikos, C Resnick, SM Wu, X Parmpi, P Clark, CM AF Davatzikos, C. Resnick, S. M. Wu, X. Parmpi, P. Clark, C. M. TI Individual patient diagnosis of AD and FTD via high-dimensional pattern classification of MRI SO NEUROIMAGE LA English DT Article DE frontotemporal dementia (29); Alzheimer's disease (26); volumetric MRI (130) ID FRONTOTEMPORAL LOBAR DEGENERATION; MILD COGNITIVE IMPAIRMENT; MACHINE LEARNING-METHODS; EARLY ALZHEIMERS-DISEASE; VOXEL-BASED MORPHOMETRY; ENTORHINAL CORTEX; BRAIN ATROPHY; HIPPOCAMPAL ATROPHY; SPATIAL-PATTERNS; OLDER-ADULTS AB The purpose of this study is to determine the diagnostic accuracy of MRI-based high-dimensional pattern classification in differentiating between patients with Alzheimer's disease (AD), Frontotemporal Dementia (FTD), and healthy controls, on an individual patient basis. MRI scans of 37 patients with AD and 37 age-matched cognitively normal elderly individuals, as well as 12 patients with FTD and 12 age-matched cognitively normal elderly individuals, were analyzed using voxel-based analysis and high-dimensional pattern classification. Diagnostic sensitivity and specificity of spatial patterns of regional brain atrophy found to be characteristic of AD and FTD were determined via cross-validation and via split-sample methods. Complex spatial patterns of relatively reduced brain volumes were identified, including temporal, orbitofrontal, parietal and cingulate regions, which were predominantly characteristic of either AD or FTD. These patterns provided 100% diagnostic accuracy, when used to separate AD or FTD from healthy controls. The ability to correctly distinguish AD from FTD averaged 84.3%. All estimates of diagnostic accuracy were determined via cross-validation. In conclusion, AD-and FTD-specific patterns of brain atrophy can be detected with high accuracy using high-dimensional pattern classification of MRI scans obtained in a typical clinical setting. (c) 2008 Elsevier Inc. All rights reserved. C1 [Davatzikos, C.; Wu, X.; Parmpi, P.] Univ Penn, Sect Biomed Image Anal, Dept Radiol, Philadelphia, PA 19104 USA. [Resnick, S. M.] NIA, Lab Personal & Cognit, Bethesda, MD 20892 USA. [Clark, C. M.] Univ Penn, Dept Neurol, Rush Alzheimers Dis Ctr, Philadelphia, PA 19104 USA. RP Davatzikos, C (reprint author), Univ Penn, Sect Biomed Image Anal, Dept Radiol, 3600 Market St,Suite 380, Philadelphia, PA 19104 USA. EM christos.davatzikos@uphs.upenn.edu FU Intramural NIH HHS [Z01 AG000191-11]; NIA NIH HHS [N01 AG032124, N01-AG-3-2124, P30 AG010124, P30 AG010124-179001, P30-AG10124, R01 AG014971, R01 AG014971-07, R01-AG14971] NR 60 TC 120 Z9 125 U1 0 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD JUL 15 PY 2008 VL 41 IS 4 BP 1220 EP 1227 DI 10.1016/j.neuroimage.2008.03.050 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 311SR UT WOS:000256620400006 PM 18474436 ER PT J AU Turk, DC Dworkin, RH Revicki, D Harding, G Burke, LB Cella, D Cleeland, CS Cowan, P Farrar, JT Hertz, S Max, MB Rappaport, BA AF Turk, Dennis C. Dworkin, Robert H. Revicki, Dennis Harding, Gale Burke, Laurie B. Cella, David Cleeland, Charles S. Cowan, Penney Farrar, John T. Hertz, Sharon Max, Mitchell B. Rappaport, Bob A. TI Identifying important outcome domains for chronic pain clinical trials: An IMMPACT survey of people with pain SO PAIN LA English DT Article DE chronic pain; patient-reported outcomes; domains; health-related quality of life ID PATIENTS PERSPECTIVE; PATIENT PERSPECTIVE; RECOMMENDATIONS; MODERATE; MILD; POINTS; SCALES; TASK AB This two-phase study was conducted to identify relevant domains of patient-reported outcomes from the perspective of people who experience chronic pain. In Phase 1, focus groups were conducted to generate a pool of patient outcome-related domains and their components. The results of the focus groups identified 19 aspects of their lives that were significantly impacted by the presence of their symptoms and for which improvements were important criteria they would use in evaluating the effectiveness of any treatment. Phase 2 was conducted to examine the importance and relevance of domains identified from a much larger and diverse sample of people with chronic pain. A survey was developed and posted on the American Chronic Pain Association website. Participants were asked to rate the importance of each item or domain identified by the focus groups on a scale of 0 to10 (i.e., 0 = "not at all important" and 10 = "extremely important"). The survey was completed by 959 individuals. The results indicate that all 19 aspects of daily life derived from the focus groups were considered important with a majority of respondents indicating a score of 8 or greater. In addition to pain reduction, the most important aspects were enjoyment of life, emotional well-being, fatigue, weakness, and sleep-related problems. Chronic pain clearly impacts health-related quality of life. The results of the two phases of the study indicate that people with chronic pain consider functioning and well-being as important areas affected by the presence of symptoms and as appropriate targets of treatment. These multiple outcomes should be considered when evaluating the efficacy and effectiveness of chronic pain treatments. (c) 2007 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Turk, Dennis C.] Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA. [Dworkin, Robert H.] Univ Rochester, Rochester, NY USA. [Revicki, Dennis; Harding, Gale] United BioSource Corp, Bethesda, MD USA. [Burke, Laurie B.; Hertz, Sharon; Rappaport, Bob A.] US FDA, Rockville, MD 20857 USA. [Cella, David] Northwestern Univ, Chicago, IL 60611 USA. [Cleeland, Charles S.] MD Anderson Canc Ctr, Houston, TX USA. [Cowan, Penney] Amer Chron Pain Assoc, Rocklin, CA USA. [Farrar, John T.] Univ Penn, Philadelphia, PA 19104 USA. [Max, Mitchell B.] Natl Inst Dent & Craniofacial Res, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Turk, DC (reprint author), Univ Washington, Dept Anesthesiol, Box 356540, Seattle, WA 98195 USA. EM turkdc@u.washington.edu RI Farrar, John/A-1037-2007 OI Farrar, John/0000-0001-8656-5157 NR 28 TC 163 Z9 163 U1 3 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JUL 15 PY 2008 VL 137 IS 2 BP 276 EP 285 DI 10.1016/j.pain.2007.09.002 PG 10 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 333UF UT WOS:000258177300007 PM 17937976 ER PT J AU Porter, LS Keefe, FJ Garst, J McBride, CM Baucom, D AF Porter, Laura S. Keefe, Francis J. Garst, Jennifer McBride, Colleen M. Baucom, Donald TI Self-efficacy for managing pain, symptoms, and function in patients with lung cancer and their informal caregivers: Associations with symptoms and distress SO PAIN LA English DT Article DE self-efficacy; symptom management; lung cancer; caregivers ID QUALITY-OF-LIFE; PSYCHOLOGICAL DISTRESS; FAMILY CAREGIVERS; GASTROINTESTINAL CANCER; VALIDATION; SCALE; INVENTORY; THERAPY; PERCEPTIONS; SPOUSES AB This study examined self-efficacy for managing pain, symptoms, and function in patients with lung cancer and their caregivers, and associations between self-efficacy and patient and caregiver adjustment. One hundred and fifty-two patients with early stage lung cancer completed measures of self-efficacy, pain, fatigue, quality of life, depression, and anxiety. Their caregivers completed a measure assessing their self-efficacy for helping the patient manage symptoms and measures of psychological distress and caregiver strain. Analyses indicated that, overall, patients and caregivers were relatively low in self-efficacy for managing pain, symptoms, and function, and that there were significant associations between self-efficacy and adjustment. Patients low in self-efficacy reported significantly higher levels of pain, fatigue, lung cancer symptoms, depression, and anxiety, and significantly worse physical and functional well being, as did patients whose caregivers were low in self-efficacy. When patients and caregivers both had low self-efficacy, patients reported higher levels of anxiety and poorer quality of life than when both were high in self-efficacy. There were also significant associations between patient and caregiver self-efficacy and caregiver adjustment, with lower levels of self-efficacy associated with higher levels of caregiver strain and psychological distress. These preliminary findings raise the possibility that patient and caregiver self-efficacy for managing pain, symptoms, and function may be important factors affecting adjustment, and that interventions targeted at increasing self-efficacy may be useful in this population. (c) 2007 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Porter, Laura S.; Keefe, Francis J.; Garst, Jennifer] Duke Univ, Med Ctr, Durham, NC 27705 USA. [McBride, Colleen M.] NIH, Bethesda, MD 20892 USA. [Baucom, Donald] Univ N Carolina, Chapel Hill, NC USA. RP Porter, LS (reprint author), Duke Univ, Med Ctr, 2200 W Main St,Suite 340, Durham, NC 27705 USA. EM laura.porter@duke.edu FU NCI NIH HHS [R01 CA91947, R01 CA091947, R01 CA091947-01A1] NR 36 TC 77 Z9 82 U1 4 U2 22 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JUL 15 PY 2008 VL 137 IS 2 BP 306 EP 315 DI 10.1016/j.pain.2007.09.010 PG 10 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 333UF UT WOS:000258177300010 PM 17942229 ER PT J AU Pinto, A Greenberg, BD Grados, MA Bienvenu, OJ Samuels, JF Murphy, DL Hasler, G Stout, RL Rauch, SL Shugart, YY Pauls, DL Knowles, JA Fyer, AJ McCracken, JT Piacentini, J Wang, Y Willour, VL Cullen, B Liang, KY Hoehn-Saric, R Riddle, MA Rasmussen, SA Nestadt, G AF Pinto, Anthony Greenberg, Benjamin D. Grados, Marco A. Bienvenu, O. Joseph Samuels, Jack F. Murphy, Dennis L. Hasler, Gregor Stout, Robert L. Rauch, Scott L. Shugart, Yin Y. Pauls, David L. Knowles, James A. Fyer, Abby J. McCracken, James T. Piacentini, John Wang, Ying Willour, Virginia L. Cullen, Bernadette Liang, Kung-Yee Hoehn-Saric, Rudolf Riddle, Mark A. Rasmussen, Steven A. Nestadt, Gerald TI Further development of YBOCS dimensions in the OCD Collaborative Genetics Study: Symptoms vs. categories SO PSYCHIATRY RESEARCH LA English DT Article DE obsessive compulsive disorder; symptoms; factors; familial; genetics ID OBSESSIVE-COMPULSIVE DISORDER; SEROTONIN REUPTAKE INHIBITORS; AFFECTED SIBLING PAIRS; LA-TOURETTE-SYNDROME; SCHIZOPHRENIA; SCALE; SUBTYPES; FAMILY; SAMPLE; FAMILIALITY AB Despite progress in identifying homogeneous subphenotypes of obsessive-compulsive disorder (OCD) through factor analysis of the Yale Brown Obsessive-Compulsive Scale Symptom Checklist (YBOCS-SC), prior solutions have been limited by a reliance on presupposed symptom categories rather than discrete symptoms. Furthermore, there have been few attempts to evaluate the familiality of OCD symptom dimensions. The purpose of this study was to extend prior work by this collaborative group in category-based dimensions by conducting the first-ever exploratory dichotomous factor analysis using individual OCD symptoms, comparing these results to a refined category-level solution, and testing the familiality of derived factors. Participants were 485 adults in the six-site OCD Collaborative Genetics Study, diagnosed with lifetime OCD using semi-structured interviews. YBOCS-SC data were factor analyzed at both the individual item and symptom category levels. Factor score intraclass correlations were calculated using a subsample of 145 independent affected sib pairs. The item- and category-level factor analyses yielded nearly identical 5-factor solutions. While significant sib-sib associations were found for four of the five factors, Hoarding and Taboo Thoughts were the most robustly familial (r(ICC) >= 0.2). This report presents considerable converging evidence for a five-factor structural model of OCD symptoms, including separate factor analyses employing individual symptoms and symptom categories, as well as sibling concordance. The results support investigation of this multidimensional model in OCD genetic linkage studies. (C) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Pinto, Anthony; Greenberg, Benjamin D.; Rasmussen, Steven A.] Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI 02906 USA. [Grados, Marco A.; Bienvenu, O. Joseph; Samuels, Jack F.; Shugart, Yin Y.; Wang, Ying; Willour, Virginia L.; Cullen, Bernadette; Liang, Kung-Yee; Hoehn-Saric, Rudolf; Riddle, Mark A.; Nestadt, Gerald] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Murphy, Dennis L.; Hasler, Gregor] NIMH, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Stout, Robert L.] Decis Sci Inst, Providence, RI USA. [Rauch, Scott L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Psychiat Neuroimaging Res Program, Charlestown, MA USA. [Rauch, Scott L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Obsess Compuls Disorders Program, Charlestown, MA USA. [Pauls, David L.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Charlestown, MA USA. [McCracken, James T.] Univ So Calif, Keck Sch Med, Dept Psychiat, Los Angeles, CA 90033 USA. [Fyer, Abby J.] Columbia Univ, Dept Psychiat, Coll Phys & Surg, New York, NY USA. [Fyer, Abby J.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [McCracken, James T.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Piacentini, John] Univ Calif Los Angeles, Sch Med, Div Child & Adolescent Psychiat, Los Angeles, CA USA. RP Pinto, A (reprint author), Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, 345 Blackstone Blvd, Providence, RI 02906 USA. EM Anthony_Pinto@brown.edu RI Piacentini, John/C-4645-2011; Liang, Kung-Yee/F-8299-2011; Hasler, Gregor/E-4845-2012; Pinto, Anthony/D-2718-2017; OI Hasler, Gregor/0000-0002-8311-0138; Pinto, Anthony/0000-0002-6078-7242; Samuels, Jack/0000-0002-6715-7905 FU NIMH NIH HHS [K23 MH064543, K23 MH064543-05, K23 MH066284, K23 MH066284-05, R01 MH050214, R01 MH050214-09, R01 MH50214] NR 55 TC 69 Z9 69 U1 1 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD JUL 15 PY 2008 VL 160 IS 1 BP 83 EP 93 DI 10.1016/j.psychres.2007.07.010 PG 11 WC Psychiatry SC Psychiatry GA 326GE UT WOS:000257645800011 PM 18514325 ER PT J AU Cropley, VL Fujita, M Bara-Jimenez, W Brown, AK Zhang, XY Sangare, J Herscovitch, P Pike, VW Hallett, M Nathan, PJ Innis, RB AF Cropley, Vanessa L. Fujita, Masahiro Bara-Jimenez, William Brown, Amira K. Zhang, Xiang-Yang Sangare, Janet Herscovitch, Peter Pike, Victor W. Hallett, Mark Nathan, Pradeep J. Innis, Robert B. TI Pre- and post-synaptic dopamine imaging and its relation with frontostriatal cognitive function in Parkinson disease: PET studies with [(11)C]NNC 112 and [(18)F]FDOPA SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE [(18)F]FDOPA; [(11)C]NNC 112; PET; Parkinson disease; frontostriatal cognition; dopamine ID POSITRON-EMISSION-TOMOGRAPHY; FRONTAL-LOBE DYSFUNCTION; PREFRONTAL CORTEX; HUMAN-BRAIN; BASAL GANGLIA; D1 RECEPTORS; D-1-DOPAMINE RECEPTORS; BINDING; PERFORMANCE; SCHIZOPHRENIA AB Frontostriatal cognitive dysfunction is common in Parkinson disease (PD), but the explanation for its heterogeneous expressions remains unclear. This study examined the dopamine system within the fromostriatal circuitry with positron emission tomography (PET) to investigate pre- and post-synaptic dopamine function in relation to the executive processes in PD. Fifteen non-demented PD patients and 14 healthy controls underwent [(18)F]FDOPA (for dopamine synthesis) and [(11)C]NNC 112 (for D(i) receptors) PET scans and cognitive testing. Parametric images of [(18)F]FDOPA uptake (K(i)) and [(11)C]NNC 112 binding potential (BPND) were calculated using reference tissue models. Group differences in K(i) and BPND were assessed with both volume of interest and statistical parametric mapping, and were correlated with cognitive tests. Measurement of [(18)F]FDOPA uptake in cerebral cortex was questionable because of higher K(i) values in white than adjacent gray matter. These paradoxical results were likely to be caused by violations of the reference tissue model assumption rendering interpretation of cortical [(18)F]FDOPA uptake in PD difficult. We found no regional differences in D(i) receptor density between controls and PD, and no overall differences in frontostriatal performance. Although D(i) receptor density did not relate to frontostriatal cognition, K(i) decreases in the putamen predicted performance on the Wisconsin Card Sorting Test in PD only. These results suggest that striatal dopamine denervation may contribute to some frontostriatal cognitive impairment in moderate stage PD. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Cropley, Vanessa L.; Innis, Robert B.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. [Bara-Jimenez, William; Hallett, Mark] NINDS, Human Motor Control Sect, Bethesda, MD 20892 USA. [Herscovitch, Peter] NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA. [Nathan, Pradeep J.] Monash Univ, Sch Psychol Psychiat & Psychol Med, Clayton, Vic, Australia. [Cropley, Vanessa L.] Swinburne Univ Technol, Brain Sci Inst, Hawthorn, Vic 3122, Australia. RP Cropley, VL (reprint author), NIMH, Mol Imaging Branch, NIH, Bldg 31,Rm B2-B37,1 Ctr Dr,MSC 0135, Bethesda, MD 20892 USA. EM vcropley@groupwise.swin.edu.au; robert.innis@nih.gov FU Intramural NIH HHS NR 68 TC 37 Z9 38 U1 2 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD JUL 15 PY 2008 VL 163 IS 2 BP 171 EP 182 DI 10.1016/j.pscychresns.2007.11.003 PG 12 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 325HY UT WOS:000257581200008 PM 18504119 ER PT J AU Wang, XQ Miller, DS Zheng, W AF Wang, Xueqian Miller, David S. Zheng, Wei TI Intracellular localization and subsequent redistribution of metal transporters in a rat choroid plexus model following exposure to manganese or iron SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE cerebrospinal fluid; blood-cerebrospinal fluid barrier; confocal microscopy; manganese; iron; divalent metal transporter; transferrin receptor; metal transporter protein ID BLOOD-CSF BARRIER; CENTRAL-NERVOUS-SYSTEM; BRAIN-BARRIER; TRANSFERRIN RECEPTOR; OXIDATIVE STRESS; ION TRANSPORTER; MESSENGER-RNA; IN-VITRO; EXPRESSION; MECHANISM AB Confocal microscopy was used to investigate the effects of manganses(Mn) and iron(Fe) exposure on the subcellular distribution of metal transporting proteins, i.e., divalent metal transporter 1(DMT1), metal transporter protein 1(MTP1), and transferrin receptor(TfR), in the rat intact choroid plexus which comprise the blood-cerebrospinal fluid barrier. In control tiIn control tissue, DMT1 was concentrated below the apical epithelial membrane, MTP1 was diffuse within the cytosol, and TfR was distributed in vesicles around nuclei. Following Mn or Fe treatement (1 and 10 mu M), the distribution of DMT1 was not affected when microtubules were disrupted. Quantitative RT-PCR and Western blot analyses revealed a significant increase in mRNA and protein levels of TfR but not DMT1 and MTP1 after Mn exposure. These results suggest that earlyevents in the tissue response to Mn or Fe exposure involve microtubule-dependent, intracellular trafficking ofMTP1 and TfR.The intracellular trafficking of metal transporters in the choroid plexus following Mn exposure may partially contribute to Mn-induced disruption in Fe homeostasis in the cerebrospinal fluid (CSF) following Mn exposure.(c) 2008 Elsevier Inc. All rights reserved. C1 [Wang, Xueqian; Zheng, Wei] Purdue Univ, Sch Hlth Sci, W Lafayette, IN 47907 USA. [Miller, David S.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Zheng, W (reprint author), Purdue Univ, Sch Hlth Sci, 550 Stadium Mail Dr,Room 1163D, W Lafayette, IN 47907 USA. EM wz18@purdue.edu FU NIEHS NIH HHS [R01 ES008146, R01 ES008146-11, R01 ES008164, R21 ES013118, R21 ES013118-02] NR 35 TC 20 Z9 21 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JUL 15 PY 2008 VL 230 IS 2 BP 167 EP 174 DI 10.1016/j.taap.2008.02.024 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 325GR UT WOS:000257577500005 PM 18420243 ER PT J AU Ingelsson, E Gona, P Larson, MG Lloyd-Jones, DM Kannel, WB Vasan, RS Levy, D AF Ingelsson, Erik Gona, Philimon Larson, Martin G. Lloyd-Jones, Donald M. Kannel, William B. Vasan, Ramachandran S. Levy, Daniel TI Altered blood pressure progression in the community and its relation to clinical events SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; CARDIOVASCULAR-DISEASE; HYPERTENSION PREVALENCE; UNITED-STATES; 7 COUNTRIES; US ADULTS; FRAMINGHAM; MORTALITY; TRENDS; RISK AB Background: Long-term blood pressure (BP) progression and its importance as a predictor of clinical outcome have not been well characterized across different periods. Methods: We evaluated period trends for 3 BP variables (long-term slope and mean BP during a baseline period of 16 years, and last baseline value) in an earlier period (1953- 1971; n = 1644, mean participant age, 61 years) and in a later period (1971-1990; n = 1040, mean participant age, 58 years) in participants in the Framingham Heart Study who initially did not have hypertension. In addition, we explored the relation of BP to cardiovascular disease incidence and all-cause mortality in the 2 periods, each with up to 16 years of follow-up. Results: Long-term slope, mean, and last baseline BP measurements were significantly lower in the later period (P <. 001). Rates of hypertension control (BP < 140/90 mmHg) were higher in the later vs the earlier period (32% vs 23%; P <. 001). Multivariate hazard ratios for the relation of BP to outcomes were generally lower in the later period; this was statistically significant for the relation of last baseline BP to all-cause mortality (hazard ratio for 1-SD increase in systolic BP, 1.02 vs 1.25, P=.03; hazard ratio for diastolic BP, 1.00 vs 1.23, P=. 04). Conclusions: We found evidence that BP levels in the community have changed over time, coinciding with improved rates of hypertension control and attenuation of BP-mortality relations. These findings are consistent with the hypothesis that hypertension treatment in the community has altered the natural history of BP progression and its relation to clinical outcome. C1 [Ingelsson, Erik; Gona, Philimon; Larson, Martin G.; Kannel, William B.; Vasan, Ramachandran S.; Levy, Daniel] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. [Ingelsson, Erik] Uppsala Univ, Dept Publ Hlth & Caring Sci, Uppsala, Sweden. [Gona, Philimon; Larson, Martin G.] Boston Univ, Sch Med, Dept Math & Stat, Cardiol Sect, Boston, MA 02118 USA. [Vasan, Ramachandran S.; Levy, Daniel] Boston Univ, Sch Med, Dept Prevent Med, Cardiol Sect, Boston, MA 02118 USA. [Lloyd-Jones, Donald M.] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Lloyd-Jones, Donald M.] Northwestern Univ, Dept Med, Bluhm Cardiovasc Inst, Feinberg Sch Med, Chicago, IL 60611 USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. RP Levy, D (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Ste 2, Framingham, MA 01702 USA. EM levyd@nih.gov RI Lloyd-Jones, Donald/C-5899-2009; OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [N01 HC025195, N01-HC-25195, N01HC25195] NR 27 TC 4 Z9 4 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUL 14 PY 2008 VL 168 IS 13 BP 1450 EP 1457 DI 10.1001/archinte.168.13.1450 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 325NH UT WOS:000257595100012 PM 18625926 ER PT J AU McArdle, PF Rutherford, S Mitchell, BD Damcott, CM Wang, Y Ramachandran, V Ott, S Chang, YPC Levy, D Steinle, N AF McArdle, Patrick F. Rutherford, Sue Mitchell, Braxton D. Damcott, Coleen M. Wang, Ying Ramachandran, Vasan Ott, Sandy Chang, Yen-Pei C. Levy, Daniel Steinle, Nanette TI Nicotinic acetylcholine receptor subunit variants are associated with blood pressure; findings in the Old Order Amish and replication in the Framingham Heart Study SO BMC MEDICAL GENETICS LA English DT Article ID CONGENITAL MYASTHENIC SYNDROME; HYPERTENSION; MUTATIONS; DISEASE; MUSCLE; KIDNEYS AB Background: Systemic blood pressure, influenced by both genetic and environmental factors, is regulated via sympathetic nerve activity. We assessed the role of genetic variation in three subunits of the neuromuscular nicotinic acetylcholine receptor positioned on chromosome 2q, a region showing replicated evidence of linkage to blood pressure. Methods: We sequenced CHRNAI, CHRND and CHRNG in 24 Amish subjects from the Amish Family Diabetes Study (AFDS) and identified 20 variants. We then performed association analysis of non-redundant variants (n = 12) in the complete AFDS cohort of 1,189 individuals, and followed by genotyping blood pressure-associated variants (n = 5) in a replication sample of 1,759 individuals from the Framingham Heart Study (FHS). Results: The minor allele of a synonymous coding SNP, rs2099489 in CHRNG, was associated with higher systolic blood pressure in both the Amish (p = 0.0009) and FHS populations (p = 0.009) (minor allele frequency = 0.20 in both populations). Conclusion: CHRNG is currently thought to be expressed only during fetal development. These findings support the Barker hypothesis, that fetal genotype and intra-uterine environment influence susceptibility to chronic diseases later in life. Additional studies of this variant in other populations, as well as the effect of this variant on acetylcholine receptor expression and function, are needed to further elucidate its potential role in the regulation of blood pressure. This study suggests for the first time in humans, a possible role for genetic variation in the neuromuscular nicotinic acetylcholine receptor, particularly the gamma subunit, in systolic blood pressure regulation. C1 [McArdle, Patrick F.; Mitchell, Braxton D.; Damcott, Coleen M.; Wang, Ying; Ott, Sandy; Chang, Yen-Pei C.; Steinle, Nanette] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Rutherford, Sue] Southwest Fdn Biomed Res, Dept Genet, San Antonio, TX USA. [Ramachandran, Vasan] Boston Univ, Sch Med, Div Cardiol, Boston, MA 02118 USA. [Levy, Daniel] NHLBI, Bethesda, MD 20892 USA. RP Steinle, N (reprint author), Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. EM pmcardle@medicine.umaryland.edu; srutherf@sfbrgenetics.org; bmitchel@medicine.umaryland.edu; cdamcott@medicine.umaryland.edu; ywang@medicine.umaryland.edu; vasan@bu.edu; sott@som.umaryland.edu; cchang@medicine.umaryland.edu; levyd@nhlbi.nih.gov; nsteinle@medicine.umaryland.edu OI Ramachandran, Vasan/0000-0001-7357-5970; Mitchell, Braxton/0000-0003-4920-4744 FU NCRR NIH HHS [M01 RR 000052, M01 RR 16500, M01 RR000052, M01 RR016500]; NHLBI NIH HHS [N01-HC-25195, N01HC25195, R01 HL076768, R01 HL76768, U01 HL072515, U01 HL72515]; NIDDK NIH HHS [R01 DK054261, P30 DK072488, R01 DK54261] NR 32 TC 4 Z9 4 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PD JUL 14 PY 2008 VL 9 AR 67 DI 10.1186/1471-2350-9-67 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 335CW UT WOS:000258269400001 PM 18625075 ER PT J AU Ashwell, JD AF Ashwell, Jonathan D. TI TWEAKing death SO JOURNAL OF CELL BIOLOGY LA English DT Editorial Material ID ALPHA-DEPENDENT APOPTOSIS; KAPPA-B ACTIVATION; CELL-DEATH; TNF SUPERFAMILY; RECEPTOR; DEGRADATION; IAPS; INHIBITOR; UBIQUITIN; PATHWAYS AB Smac mimetics (inhibitor of apoptosis [IAP] antagonists) are synthetic reagents that kill susceptible tumor cells by inducing degradation of cellular IAP (cIAP) 1 and cIAP2, nuclear factor kappa B activation, tumor necrosis factor (TNF) alpha production, TNF receptor 1 occupancy, and caspase-8 activation. In this issue of The Journal of Cell Biology, Vince et al. (see p. 171) report remarkable similarities in the events leading to tumor cell death triggered by the cytokine TWEAK (TNF-like weak inducer of apoptosis) and IAP antagonists. Although the mechanistic details differ, a common and necessary feature that is also shared by TNF receptor 2 signaling is reduction in the level of cIAP1 and, in some cases, cIAP2 and TNF receptor-associated factor 2. These findings not only extend our appreciation of how cell death pathways are kept in check in tumors, they reinforce the possible utility of induced cIDE (cIAP deficiency) in the selective elimination of neoplastic cells. C1 Natl Canc Inst, Natl Inst Hlth, Ctr Canc Res, Lab Immune Cell Biol, Bethesda, MD 20892 USA. RP Ashwell, JD (reprint author), Natl Canc Inst, Natl Inst Hlth, Ctr Canc Res, Lab Immune Cell Biol, Bethesda, MD 20892 USA. EM jda@pop.nci.nih.gov NR 21 TC 5 Z9 5 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUL 14 PY 2008 VL 182 IS 1 BP 15 EP 17 DI 10.1083/jcb.200806036 PG 3 WC Cell Biology SC Cell Biology GA 331VW UT WOS:000258041700004 PM 18606854 ER PT J AU Mendoza, FN Lopez-Lemus, J Chapela, GA Alejandre, J AF Mendoza, Francisco Noe Lopez-Lemus, Jorge Chapela, Gustavo A. Alejandre, Jose TI The Wolf method applied to the liquid-vapor interface of water SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID MOLECULAR-DYNAMICS SIMULATIONS; PERIODIC SLAB GEOMETRIES; LENNARD-JONES FLUIDS; COULOMBIC INTERACTIONS; COMPUTER-SIMULATIONS; LATTICE SUMS; SYSTEMS; ELECTROSTATICS; SUMMATION AB The Wolf method for the calculation of electrostatic interactions is applied in a liquid phase and at the liquid-vapor interface of water and its results are compared with those from the Ewald sums method. Molecular dynamics simulations are performed to calculate the radial distribution functions at room temperature. The interface simulations are used to obtain the coexisting densities and surface tension along the coexistence curve. The water model is a flexible version of the extended simple point charge model. The Wolf method gives good structural results, fair coexistence densities, and poor surface tensions as compared with those obtained using the Ewald sums method. (C) 2008 American Institute of Physics. C1 [Mendoza, Francisco Noe; Alejandre, Jose] Univ Autonoma Metropolitana Iztapalapa, Dept Quim, Mexico City 09340, DF, Mexico. [Mendoza, Francisco Noe] NIEHS, Durham, NC 27709 USA. [Lopez-Lemus, Jorge] Univ Autonoma Estado Mexico, Fac Ciencias, Toluca 50000, CP, Mexico. [Chapela, Gustavo A.] Univ Autonoma Metropolitana Iztapalapa, Dept Fis, Mexico City 09340, DF, Mexico. RP Alejandre, J (reprint author), Univ Autonoma Metropolitana Iztapalapa, Dept Quim, Av San Rafael Atlixco 186,Col Vicentina, Mexico City 09340, DF, Mexico. EM jra@xanum.uam.mx RI Alejandre, Jose/B-3191-2015; Lopez, Jorge/A-3328-2016 OI Alejandre, Jose/0000-0003-3158-6027; Lopez, Jorge/0000-0002-9486-6942 NR 26 TC 18 Z9 18 U1 0 U2 9 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD JUL 14 PY 2008 VL 129 IS 2 AR 024706 DI 10.1063/1.2948951 PG 6 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 326AA UT WOS:000257629100043 ER PT J AU Zou, KH Liu, A AF Zou, Kelly H. Liu, Aiyi TI Theme issue 'mathematical and statistical methods for diagnoses and therapies' - Preface SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES LA English DT Editorial Material C1 [Liu, Aiyi] NICHHD, Rockville, MD 20852 USA. [Zou, Kelly H.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Liu, A (reprint author), NICHHD, 6100 Execut Blvd, Rockville, MD 20852 USA. EM kh_zou@yahoo.com; liua@mail.nih.gov NR 7 TC 0 Z9 0 U1 0 U2 0 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 1364-503X J9 PHILOS T R SOC A JI Philos. Trans. R. Soc. A-Math. Phys. Eng. Sci. PD JUL 13 PY 2008 VL 366 IS 1874 BP 2251 EP 2252 DI 10.1098/rsta.2008.0046 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 303US UT WOS:000256067000001 PM 18407891 ER PT J AU Liu, AY Wu, CQ Yu, KF AF Liu, Aiyi Wu, Chengqing Yu, Kai F. TI Two-stage procedures for selecting the best diagnostic biomarkers SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES LA English DT Article DE classification rate; diagnosis; nuisance parameters; probability of correct selection; sensitivity; specificity AB Considered in the paper is the problem of selecting a diagnostic biomarker that has the highest classification rate among several candidate markers with dichotomous outcomes. The probability of correct selection depends on a number of nuisance parameters from the joint distribution of the biomarkers and thus can be substantially affected if these nuisance parameters are misspecified. A two-stage procedure is proposed to compute the needed sample size that achieves the desired level of correct selection, as so confirmed by simulation results. C1 [Liu, Aiyi; Yu, Kai F.] NICHHD, Biomet & Math Stat Branch, Rockville, MD 20852 USA. [Wu, Chengqing] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. RP Liu, A (reprint author), NICHHD, Biomet & Math Stat Branch, 6100 Execut Blvd, Rockville, MD 20852 USA. EM liua@mail.nih.gov OI Liu, Aiyi/0000-0002-6618-5082 FU Intramural NIH HHS NR 6 TC 0 Z9 0 U1 0 U2 0 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 1364-503X J9 PHILOS T R SOC A JI Philos. Trans. R. Soc. A-Math. Phys. Eng. Sci. PD JUL 13 PY 2008 VL 366 IS 1874 BP 2293 EP 2299 DI 10.1098/rsta.2008.0032 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 303US UT WOS:000256067000005 PM 18407902 ER PT J AU Shu, Y Liu, AY Li, ZH AF Shu, Yu Liu, Aiyi Li, Zhaohai TI Point and interval estimation of accuracies of a binary medical diagnostic test following group sequential testing SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES LA English DT Article DE group sequential tests; sensitivity; specificity; Woodroofe pivot method ID CONFIDENCE-INTERVALS; TRIAL AB When hypotheses concerning the sensitivity and specificity of a binary medical diagnostic test are simultaneously tested using a group sequential procedure, constructing point and interval estimates of the parameters is challenging because there is no unique way to order sample points in the two-dimensional space. In this paper, upon termination of a group sequential procedure, we compare the bias and mean squared errors of the maximum-likelihood and Rao Blackwell unbiased estimators of sensitivity and specificity. Confidence intervals (CIs) of the two parameters were constructed using normal approximation and Woodroofe's pivot methods based on maximum-likelihood and Rao Blackwell unbiased estimates. The coverage probability and the expected length of CIs for the parameters were compared by simulation studies. C1 [Shu, Yu] Abbott Labs, Abbott Pk, IL 60064 USA. [Liu, Aiyi; Li, Zhaohai] NICHHD, Biometry & Math Stat Branch, Rockville, MD 20852 USA. [Li, Zhaohai] George Washington Univ, Dept Stat, Washington, DC 20037 USA. RP Shu, Y (reprint author), Abbott Labs, Bldg AP9A-1,100 Abbott Pk Rd, Abbott Pk, IL 60064 USA. EM yu.shu@abbott.com OI Liu, Aiyi/0000-0002-6618-5082 NR 14 TC 0 Z9 0 U1 1 U2 6 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 1364-503X J9 PHILOS T R SOC A JI Philos. Trans. R. Soc. A-Math. Phys. Eng. Sci. PD JUL 13 PY 2008 VL 366 IS 1874 BP 2335 EP 2345 DI 10.1098/rsta.2008.0041 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 303US UT WOS:000256067000008 PM 18407894 ER PT J AU Yu, BB Gastwirth, JL AF Yu, Binbing Gastwirth, Joseph L. TI A method of assessing the sensitivity of the Cochran-Mantel-Haenszel test to an unobserved confounder SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES LA English DT Article DE Cochran-Mantel-Haenszel test; confounders; sensitivity analysis; stratification ID PROPENSITY SCORE; SUBCLASSIFICATION AB Observational studies, including the case-control design frequently used in epidemiology, are subject to a number of biases and possible confounding factors. Failure to adjust with them may lead to an erroneous conclusion about the existence of a causal relationship between exposure and disease. The Cochran Mantel Haenszel (CMH) test is widely used to measure the strength of the association between an exposure and disease or response, after stratifying on the observed covariates. Thus, observed confounders are accounted for in the analysis. In practice, there may be causal variables that are unknown or difficult to obtain. Hence, they are not incorporated into the analysis. Sensitivity analysis enables investigators to assess the robustness of the findings. A method for assessing the sensitivity of the CMH test to an omitted confounder is presented here. The technique is illustrated by re-examining two datasets: one concerns the effect of maternal hypertension as a risk factor for low birth weight infants and the other focuses on the risk of allopurinol on having a rash. The computer code performing the sensitivity analysis is provided in appendix A. C1 [Yu, Binbing] NIA, Lan Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Gastwirth, Joseph L.] George Washington Univ, Dept Stat, Washington, DC 20037 USA. RP Yu, BB (reprint author), NIA, Lan Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. EM yubi@mail.nih.gov FU Intramural NIH HHS [Z99 AG999999] NR 20 TC 3 Z9 4 U1 0 U2 1 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 1364-503X J9 PHILOS T R SOC A JI Philos. Trans. R. Soc. A-Math. Phys. Eng. Sci. PD JUL 13 PY 2008 VL 366 IS 1874 BP 2377 EP 2388 DI 10.1098/rsta.2008.0030 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 303US UT WOS:000256067000011 PM 18407900 ER PT J AU Yang, JC AF Yang, James C. TI Vitespen: a vaccine for renal cancer? SO LANCET LA English DT Editorial Material ID MELANOMA C1 NCI, Surg Branch, Bethesda, MD 20892 USA. RP Yang, JC (reprint author), NCI, Surg Branch, Bldg 10, Bethesda, MD 20892 USA. EM jamesyang@mail.nih.gov NR 7 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD JUL 12 PY 2008 VL 372 IS 9633 BP 92 EP 93 DI 10.1016/S0140-6736(08)60698-4 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 324XJ UT WOS:000257552400006 PM 18602687 ER PT J AU Becquet, R Mofenson, LA AF Becquet, Renaud Mofenson, Lynne A. TI Early antiretroviral therapy of HIV-infected infants in resource-limited countries: possible, feasible, effective and challenging SO AIDS LA English DT Editorial Material ID TO-CHILD TRANSMISSION; CD4 CELL RESPONSE; HIV-1-INFECTED CHILDREN; UNITED-KINGDOM; FOLLOW-UP; NEVIRAPINE; MORTALITY; SINGLE; IMMUNODEFICIENCY; ADOLESCENTS C1 [Becquet, Renaud] Univ Bordeaux 2, ISPED, INSERM, Unite 897, F-33076 Bordeaux, France. [Becquet, Renaud] Univ Bordeaux 2, Ctr Rech Epidemiol & Biostat, INSERM, Unite 897, F-33076 Bordeaux, France. [Mofenson, Lynne A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Ctr Res Mothers & Children, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD USA. RP Becquet, R (reprint author), Univ Bordeaux 2, ISPED, INSERM, Unite 897, 146 Rue Leo Saignat, F-33076 Bordeaux, France. EM Renaud.Becquet@isped.u-bordeaux2.fr RI Becquet, Renaud/F-4837-2013; OI Becquet, Renaud/0000-0003-3277-0985; Mofenson, Lynne/0000-0002-2818-9808 FU Intramural NIH HHS [NIH0010050393] NR 33 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JUL 11 PY 2008 VL 22 IS 11 BP 1365 EP 1368 PG 4 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 326WM UT WOS:000257689800014 PM 18580616 ER PT J AU Krawczyk, E Hanover, JA Schlegel, R Suprynowicz, FA AF Krawczyk, Ewa Hanover, John A. Schlegel, Richard Suprynowicz, Frank A. TI Karyopherin beta 3: A new cellular target for the HPV-16 E5 oncoprotein SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE HPV-16; E5 oncoprotein; karyopherin beta 3 ID HUMAN-PAPILLOMAVIRUS TYPE-16; GROWTH-FACTOR RECEPTOR; NUCLEAR IMPORT RECEPTORS; MINOR CAPSID PROTEIN; EPITHELIAL-CELLS; INTERACTS; BETA; TRANSFORMATION; IDENTIFICATION; ACTIVATION AB Epidemiological and experimental studies have shown that high-risk human papillomaviruses (HPVs) are the causative agents of cervical cancer worldwide, and that HPV-16 is associated with more than half of these cases. In addition to the well-characterized E6 and E7 oncoproteins of HPV-16, recent evidence increasingly has implicated the HPV-16 E5 protein (16E5) as an important mediator of oncogenic transformation. Since 16E5 has no known intrinsic enzymatic activity, its effects on infected cells are most likely mediated by interactions with various cellular proteins and/or its documented association with lipid rafts. In the present study, we describe a new cellular target that binds to 16E5 in COS cells and in stable human ectocervical cell lines. This target is karyopherin beta 3, a member of the nuclear import receptor family with critical roles in the nuclear import of ribosomal proteins and in the secretory pathway. (C) 2008 Elsevier Inc. All rights reserved. C1 [Krawczyk, Ewa; Schlegel, Richard; Suprynowicz, Frank A.] Georgetown Univ, Sch Med, Dept Pathol, Washington, DC 20057 USA. [Hanover, John A.] NIDDK, Lab Cell Biochem & Biol, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Suprynowicz, FA (reprint author), Georgetown Univ, Sch Med, Dept Pathol, 3900 Reservoir Rd NW, Washington, DC 20057 USA. EM suprynfa@georgetown.edu FU NCI NIH HHS [R01 CA053371, R01 CA053371-09, R01-CA053371] NR 35 TC 21 Z9 21 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 11 PY 2008 VL 371 IS 4 BP 684 EP 688 DI 10.1016/j.bbrc.2008.04.122 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 310CN UT WOS:000256506600021 PM 18455505 ER PT J AU An, JJ Gharami, K Liao, GY Woo, NH Lau, AG Vanevski, F Torre, ER Jones, KR Feng, Y Lu, B Xu, B AF An, Juan Ji Gharami, Kusumika Liao, Guey-Ying Woo, Newton H. Lau, Anthony G. Vanevski, Filip Torre, Enrique R. Jones, Kevin R. Feng, Yue Lu, Bai Xu, Baoji TI Distinct role of long 3 ' UTR BDNF mRNA in spine morphology and synaptic plasticity in hippocampal neurons SO CELL LA English DT Article ID DENDRITIC PROTEIN-SYNTHESIS; NEUROTROPHIC FACTOR; TERM POTENTIATION; KNOCKOUT MICE; REGULATORY MECHANISMS; RECEPTOR; TRANSLATION; TRKB; TRANSMISSION; ELEMENT AB The brain produces two brain-derived neurotrophic factor (BDNF) transcripts, with either short or long 30 untranslated regions (30 UTRs). The physiological significance of the two forms of mRNAs encoding the same protein is unknown. Here, we show that the short and long 30 UTR BDNF mRNAs are involved in different cellular functions. The short 30 UTR mRNAs are restricted to somata, whereas the long 30 UTR mRNAs are also localized in dendrites. In a mouse mutant where the long 30 UTR is truncated, dendritic targeting of BDNF mRNAs is impaired. There is little BDNF in hippocampal dendrites despite normal levels of total BDNF protein. This mutant exhibits deficits in pruning and enlargement of dendritic spines, as well as selective impairment in long-term potentiation in dendrites, but not somata, of hippocampal neurons. These results provide insights into local and dendritic actions of BDNF and reveal a mechanism for differential regulation of subcellular functions of proteins. C1 [An, Juan Ji; Gharami, Kusumika; Liao, Guey-Ying; Vanevski, Filip; Xu, Baoji] Georgetown Univ, Sch Med, Dept Pharmacol, Washington, DC 20057 USA. [Woo, Newton H.; Lu, Bai] NICHHD, Sect Neural Dev & Plast, Bethesda, MD 20892 USA. [Lau, Anthony G.; Feng, Yue] Emory Univ, Dept Pharmacol, Atlanta, GA 30322 USA. [Torre, Enrique R.] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. [Jones, Kevin R.] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA. RP Xu, B (reprint author), Georgetown Univ, Sch Med, Dept Pharmacol, Washington, DC 20057 USA. EM bx3@georgetown.edu RI Lu, Bai/A-4018-2012; OI Feng, Yue/0000-0002-7905-2182 FU NINDS NIH HHS [NS050596, R01 NS050596, R01 NS050596-01A1, R01 NS050596-01A1S1, R01 NS050596-02, R01 NS050596-03, R56 NS050596] NR 49 TC 276 Z9 285 U1 7 U2 23 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD JUL 11 PY 2008 VL 134 IS 1 BP 175 EP 187 DI 10.1016/j.cell.2008.05.045 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 324IU UT WOS:000257513100023 PM 18614020 ER PT J AU DeHaven, WI Smyth, JT Boyles, RR Bird, GS Putney, JW AF DeHaven, Wayne I. Smyth, Jeremy T. Boyles, Rebecca R. Bird, Gary S. Putney, James W., Jr. TI Complex actions of 2-aminoethyldiphenyl borate on store-operated calcium entry SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INOSITOL TRISPHOSPHATE RECEPTOR; ACTIVATED CA2+ CHANNELS; EMBRYONIC KIDNEY-CELLS; PLASMA-MEMBRANE; CRAC CHANNEL; 2-AMINOETHOXYDIPHENYL BORATE; PHOSPHOLIPASE-C; STIM1; ORAI1; SENSOR AB Store-operated Ca(2+) entry (SOCE) is likely the most common mode of regulated influx of Ca(2+) into cells. However, only a limited number of pharmacological agents have been shown to modulate this process. 2-Aminoethyldiphenyl borate (2-APB) is a widely used experimental tool that activates and then inhibits SOCE and the underlying calcium release-activated Ca(2+) current (I(CRAC)). The mechanism by which depleted stores activates SOCE involves complex cellular movements of an endoplasmic reticulum Ca(2+) sensor, STIM1, which redistributes to puncta near the plasma membrane and, in some manner, activates plasma membrane channels comprising Orai1, -2, and -3 subunits. We show here that 2-APB blocks puncta formation of fluorescently tagged STIM1 in HEK293 cells. Accordingly, 2-APB also inhibited SOCE and I(CRAC)-like currents in cells co-expressing STIM1 with the CRAC channel subunit, Orai1, with similar potency. However, 2-APB inhibited STIM1 puncta formation less well in cells co-expressing Orai1, indicating that the inhibitory effects of 2-APB are not solely dependent upon STIM1 reversal. Further, 2-APB only partially inhibited SOCE and current in cells co-expressing STIM1 and Orai2 and activated sustained currents in HEK293 cells expressing Orai3 and STIM1. Interestingly, the Orai3-dependent currents activated by 2-APB showed large outward currents at potentials greater than +50 mV. Finally, Orai3, and to a lesser extent Orai1, could be directly activated by 2-APB, independently of internal Ca(2+) stores and STIM1. These data reveal novel and complex actions of 2-APB effects on SOCE that can be attributed to effects on both STIM1 as well as Orai channel subunits. C1 [DeHaven, Wayne I.; Smyth, Jeremy T.; Boyles, Rebecca R.; Bird, Gary S.; Putney, James W., Jr.] NIEHS, Lab Signal Transduct, Natl Inst Hlth, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Putney, JW (reprint author), NIEHS, Lab Signal Transduct, Natl Inst Hlth, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. EM putney@niehs.nih.gov OI Boyles, Rebecca/0000-0003-0073-6854 FU Intramural NIH HHS NR 38 TC 136 Z9 138 U1 0 U2 10 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 11 PY 2008 VL 283 IS 28 BP 19265 EP 19273 DI 10.1074/jbc.M801535200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 322PK UT WOS:000257387600012 PM 18487204 ER PT J AU Boshoff, HIM Xu, X Tahlan, K Dowd, CS Pethe, K Camacho, LR Park, TH Yun, CS Schnappinger, D Ehrt, S Williams, KJ Barry, CE AF Boshoff, Helena I. M. Xu, Xia Tahlan, Kapil Dowd, Cynthia S. Pethe, Kevin Camacho, Luis R. Park, Tae-Ho Yun, Chang-Soo Schnappinger, Dirk Ehrt, Sabine Williams, Kerstin J. Barry, Clifton E., III TI Biosynthesis and recycling of nicotinamide cofactors in Mycobacterium tuberculosis - An essential role for NAD in nonreplicating bacilli SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PYRIDINE-NUCLEOTIDE CYCLE; COMPLETE GENOME SEQUENCE; ADENINE-DINUCLEOTIDE; CRYSTAL-STRUCTURE; TUBERCLE BACILLI; ACID PHOSPHORIBOSYLTRANSFERASE; HAEMOPHILUS-INFLUENZAE; ESCHERICHIA-COLI; OXIDATIVE STRESS; DRUG-RESISTANCE AB Despite the presence of genes that apparently encode NAD salvage-specific enzymes in its genome, it has been previously thought that Mycobacterium tuberculosis can only synthesize NAD de novo. Transcriptional analysis of the de novo synthesis and putative salvage pathway genes revealed an up-regulation of the salvage pathway genes in vivo and in vitro under conditions of hypoxia. [(14)C] Nicotinamide incorporation assays in M. tuberculosis isolated directly from the lungs of infected mice or from infected macrophages revealed that incorporation of exogenous nicotinamide was very efficient in in vivo-adapted cells, in contrast to cells grown aerobically in vitro. Two putative nicotinic acid phosphoribosyltransferases, PncB1 (Rv1330c) and PncB2 (Rv0573c), were examined by a combination of in vitro enzymatic activity assays and allelic exchange studies. These studies revealed that both play a role in cofactor salvage. Mutants in the de novo pathway died upon removal of exogenous nicotinamide during active replication in vitro. Cell death is induced by both cofactor starvation and disruption of cellular redox homeostasis as electron transport is impaired by limiting NAD. Inhibitors of NAD synthetase, an essential enzyme common to both recycling and de novo synthesis pathways, displayed the same bactericidal effect as sudden NAD starvation of the de novo pathway mutant in both actively growing and nonreplicating M. tuberculosis. These studies demonstrate the plasticity of the organism in maintaining NAD levels and establish that the two enzymes of the universal pathway are attractive chemotherapeutic targets for active as well as latent tuberculosis. C1 [Boshoff, Helena I. M.; Xu, Xia; Tahlan, Kapil; Barry, Clifton E., III] NIAID, Tuberculosis Res Sect, Lab Clin Infect Dis, Natl Inst Hlth, Bethesda, MD 20892 USA. [Pethe, Kevin; Camacho, Luis R.] Novartis Inst Trop Dis, Singapore 138670, Singapore. [Park, Tae-Ho; Yun, Chang-Soo] Korea Res Inst Chem Technol, Ctr Anti Infect Agents Res, Drug Discovery Div, Taejon 305600, South Korea. [Schnappinger, Dirk; Ehrt, Sabine] Weill Cornell Med Coll, Dept Microbiol & Immunol, New York, NY 10065 USA. [Williams, Kerstin J.] Univ London Imperial Coll Sci Technol & Med, Dept Microbiol, Ctr Mol Microbiol & Infect, London SW7 2AZ, England. RP Boshoff, HIM (reprint author), 33 N Dr,Bldg 33 Rm, Bethesda, MD 20892 USA. EM HBOSHOFF@niaid.nih.gov RI Pethe, Kevin/D-4505-2011; Barry, III, Clifton/H-3839-2012; Pethe, Kevin/L-1199-2013; Pethe, Kevin/F-9495-2015 OI Pethe, Kevin/0000-0003-0297-0150; FU Intramural NIH HHS; Wellcome Trust NR 55 TC 69 Z9 79 U1 1 U2 14 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 11 PY 2008 VL 283 IS 28 BP 19329 EP 19341 DI 10.1074/jbc.M800694200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 322PK UT WOS:000257387600019 PM 18490451 ER PT J AU Coppin, JF Qu, W Waalkes, MP AF Coppin, Jean-Francois Qu, Wei Waalkes, Michael P. TI Interplay between cellular methyl metabolism and adaptive efflux during oncogenic transformation from chronic arsenic exposure in human cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID S-ADENOSYLHOMOCYSTEINE-HYDROLASE; INDUCED MALIGNANT-TRANSFORMATION; PROSTATIC EPITHELIAL-CELLS; DNA METHYLATION; GENE-EXPRESSION; GLUTATHIONE DEPLETION; RAT-LIVER; SODIUM ARSENITE; GENOMIC DNA; HOMOCYSTEINE AB After protracted low level arsenic exposure, the normal human prostate epithelial cell line RWPE-1 acquires a malignant phenotype with DNA hypomethylation, indicative of disrupted methyl metabolism, and shows arsenic adaptation involving glutathione overproduction and enhanced arsenic efflux. Thus, the interplay between methyl and glutathione metabolism during this progressive arsenic adaptation was studied. Arsenic-treated cells showed a time-dependent increase in LC(50) and a marked increase in homocysteine (Hcy) levels. A marked suppression of S-adenosylmethionine (SAM) levels occurred with decreased methionine adenosyltransferase 2A (converts methionine to SAM) expression and increased negative regulator methionine adenosyltransferase B, suggesting reduced conversion of Hcy to SAM. Consistent with Hcy overproduction, activity and expression of S-adenosylhomocysteine hydrolase (converts S-adenosylhomocysteine to Hcy) were both increased. Expression of cystathionine beta-synthase, a key gene in the transsulfuration pathway, and various glutathione production genes were increased, resulting in a 5-fold increase in glutathione. Arsenic efflux increased along with expression of ATP-binding cassette protein C1, which effluxes arsenic as a glutathione conjugate. Evidence of genomic DNA hypomethylation was observed during early arsenic exposure, indicating that the disruption in methyl metabolism had a potential impact related to oncogenesis. Thus, cellular arsenic adaptation is a dynamic, progressive process that involves decreased SAM recycling and concurrent accumulation of Hcy, which is channeled via transsulfuration to increase glutathione and enhance arsenic efflux but may also impact the carcinogenic process. C1 [Coppin, Jean-Francois; Qu, Wei; Waalkes, Michael P.] NCI, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. RP Waalkes, MP (reprint author), NIEHS, NCI, POB 12233,Mail Drop F0-09,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM waalkes@niehs.nih.gov FU Intramural NIH HHS NR 51 TC 43 Z9 47 U1 1 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 11 PY 2008 VL 283 IS 28 BP 19342 EP 19350 DI 10.1074/jbc.M802942200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 322PK UT WOS:000257387600020 PM 18487201 ER PT J AU Giudici, C Raynal, N Wiedemann, H Cabral, WA Marini, JC Timpl, R Bachinger, HP Farndale, RW Sasaki, T Tenni, R AF Giudici, Camilla Raynal, Nicolas Wiedemann, Hanna Cabral, Wayne A. Marini, Joan C. Timpl, Rupert Baechinger, Hans Peter Farndale, Richard W. Sasaki, Takako Tenni, Ruggero TI Mapping of SPARC/BM-40/osteonectin-binding sites on fibrillar collagens SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRIPLE-HELICAL PEPTIDES; VON-WILLEBRAND-FACTOR; MATRIX PROTEIN BM-40; BINDING-SITES; I COLLAGEN; AFFINITY BINDING; STRUCTURAL BASIS; PROCOLLAGEN-I; OSTEOGENESIS IMPERFECTA; DIRECTED MUTAGENESIS AB The 33-kDa matrix protein SPARC (BM-40, osteonectin) binds several collagen types with moderate affinity. The collagen-binding site resides in helix alpha A of the extracellular calcium-binding domain of SPARC and is partially masked by helix alpha C. Previously, we found that the removal of helix alpha C caused a 10-fold increase in the affinity of SPARC for collagen, and we identified amino acids crucial for binding by site-directed mutagenesis. In this study, we used rotary shadowing, CNBr peptides, and synthetic peptides to map binding sites of SPARC onto collagens I, II, and III. Rotary shadowing and electron microscopy of SPARC-collagen complexes identified a major binding site similar to 180 nm from the C terminus of collagen. SPARC binding was also detected with lower frequency near the matrix metalloproteinase cleavage site. These data fit well with our analysis of SPARC binding to CNBr peptides, denaturation of which abolished binding, indicating triple-helical conformation of collagen to be essential. SPARC binding was substantially decreased in two of seven alpha 2(I) mutant procollagen I samples and after N-acetylation of Lys/Hyl side chains in wild-type collagen. Synthetic peptides of collagen III were used to locate the binding sites, and we found SPARC binding activity in a synthetic triple-helical peptide containing the sequence GPOGPSGPRGQOGVMGFOGPKGNDGAO (where O indicates 4-hydroxyproline), with affinity for SPARC comparable with that of procollagen III. This sequence is conserved among alpha chains of collagens I, II, III, and V. In vitro collagen fibrillogenesis was delayed in the presence of SPARC, suggesting that SPARC might modulate collagen fibril assembly in vivo. C1 [Baechinger, Hans Peter; Sasaki, Takako] Shriners Hosp Children, Portland Res Ctr, Portland, OR 97239 USA. [Giudici, Camilla; Wiedemann, Hanna; Sasaki, Takako] Max Planck Inst Biochem, D-82152 Martinsried, Germany. [Giudici, Camilla; Tenni, Ruggero] Univ Pavia, Dept Biochem A Castellani, I-27100 Pavia, Italy. [Raynal, Nicolas; Farndale, Richard W.] Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England. [Cabral, Wayne A.; Marini, Joan C.] NICHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD 20892 USA. [Baechinger, Hans Peter; Sasaki, Takako] Oregon Hlth & Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97239 USA. RP Sasaki, T (reprint author), Shriners Hosp Children, Portland Res Ctr, 3101 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM txs@shcc.org FU Medical Research Council [G0400701]; Wellcome Trust NR 63 TC 47 Z9 49 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 11 PY 2008 VL 283 IS 28 BP 19551 EP 19560 DI 10.1074/jbc.M710001200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 322PK UT WOS:000257387600041 PM 18487610 ER PT J AU Ilagan, RP Tiso, M Konas, DW Hemann, C Durra, D Hille, R Stuehr, DJ AF Ilagan, Robielyn P. Tiso, Mauro Konas, David W. Hemann, Craig Durra, Deborah Hille, Russ Stuehr, Dennis J. TI Differences in a conformational equilibrium distinguish catalysis by the endothelial and neuronal nitric-oxide synthase flavoproteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN CYTOCHROME-P450 REDUCTASE; AUTOINHIBITORY CONTROL ELEMENT; HUMAN METHIONINE SYNTHASE; ONE-ELECTRON TRANSFER; C-TERMINAL TAIL; FERREDOXIN-NADP(+) REDUCTASE; COENZYME BINDING; REDOX PROPERTIES; 2 FLAVINS; CRYSTAL-STRUCTURE AB Nitric oxide (NO) is a physiological mediator synthesized by NO synthases (NOS). Despite their structural similarity, endothelial NOS (eNOS) has a 6-fold lower NO synthesis activity and 6-16-fold lower cytochrome c reductase activity than neuronal NOS (nNOS), implying significantly different electron transfer capacities. We utilized purified reductase domain constructs of either enzyme (bovine eNOSr and rat nNOSr) to investigate the following three mechanisms that may control their electron transfer: (i) the set point and control of a two-state conformational equilibrium of their FMN subdomains; (ii) the flavin midpoint reduction potentials; and (iii) the kinetics of NOSr-NADP(+) interactions. Although eNOSr and nNOSr differed in their NADP(H) interaction and flavin thermodynamics, the differences were minor and unlikely to explain their distinct electron transfer activities. In contrast, calmodulin (CaM)-free eNOSr favored the FMN-shielded (electron-accepting) conformation over the FMN-deshielded (electron-donating) conformation to a much greater extent than did CaM-free nNOSr when the bound FMN cofactor was poised in each of its three possible oxidation states. NADPH binding only stabilized the FMN-shielded conformation of nNOSr, whereas CaM shifted both enzymes toward the FMN-deshielded conformation. Analysis of cytochrome c reduction rates measured within the first catalytic turnover revealed that the rate of conformational change to the FMN-deshielded state differed between eNOSr and nNOSr and was rate-limiting for either CaM-free enzyme. We conclude that the set point and regulation of the FMN conformational equilibrium differ markedly in eNOSr and nNOSr and can explain the lower electron transfer activity of eNOSr. C1 [Ilagan, Robielyn P.; Durra, Deborah; Stuehr, Dennis J.] Cleveland Clin, Dept Pathobiol, Lerner Res Inst, Cleveland, OH 44195 USA. [Tiso, Mauro] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Konas, David W.] Montclair State Univ, Dept Chem & Biochem, Montclair, NJ 07043 USA. [Hemann, Craig] Ohio State Univ, Davis Heart & Lung Res Inst, Columbus, OH 43210 USA. [Hille, Russ] Univ Calif Riverside, Dept Biochem, Riverside, CA 92521 USA. RP Stuehr, DJ (reprint author), Cleveland Clin, Dept Pathobiol, Lerner Res Inst, NC-22,9500 Euclid Ave, Cleveland, OH 44195 USA. EM stuehrd@ccf.org OI Hemann, Craig/0000-0002-7380-4072 FU NCI NIH HHS [CA53914]; NHLBI NIH HHS [HL76491]; NIEHS NIH HHS [ES012658]; NIGMS NIH HHS [GM075036] NR 67 TC 36 Z9 37 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 11 PY 2008 VL 283 IS 28 BP 19603 EP 19615 DI 10.1074/jbc.M802914200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 322PK UT WOS:000257387600046 PM 18487202 ER PT J AU Weisz, A Ito, Y AF Weisz, Adrian Ito, Yoichiro TI Preparative purification of 4-hydroxy-1-naphthalenesulfonic acid sodium salt by high-speed counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE counter-current chromatography; color additive intermediate; purification; 4-hydroxy-1-naphthalenesulfonic acid sodium salt AB Among the many applications of 4-hydroxy-1-naphthalenesulfonic acid sodium salt (HNSA, CAS No. 6099-57-6) is its use as a common intermediate in the manufacture of dyes used as color additives. In order to develop an HPLC method to analyze HNSA in such additives, it was necessary to obtain pure HNSA as a reference material. This compound is only commercially available in "technical" or "practical" grade (similar to 70-85% purity). Unsatisfactory results were encountered during the attempts to eliminate impurities using published preparative purification methods. The current work demonstrates the successful application of high-speed counter-current chromatography (HSCCC) to the preparative purification of "practical" grade HNSA. The purifications of 0.55 g and 1.00 g portions were achieved by using a solvent system that consisted of n-butanol/water (1: 1), acidified with 0.2% trifluoroacetic acid. In contrast to the procedure involved in previous HSCCC separations of aromatic sulfortates, it was not necessary to add a ligand and a retainer to the solvent system for these separations. The resulting yields were 320 mg and 485 mg of HNSA, respectively, of over 99% purity. Elemental analysis, HPLC (at 240 nm), UV and high-resolution MS analyses confirmed the identity and purity of the HNSA obtained. Published by Elsevier B.V. C1 [Weisz, Adrian] US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Ito, Yoichiro] NHLBI, Bioseparat Technol Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. RP Weisz, A (reprint author), US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM adrian.weisz@fda.hhs.gov FU Intramural NIH HHS [Z99 HL999999] NR 15 TC 7 Z9 7 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD JUL 11 PY 2008 VL 1198 BP 232 EP 234 DI 10.1016/j.chroma.2008.05.060 PG 3 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 324UT UT WOS:000257545600033 PM 18541251 ER PT J AU Reddy, A Wang, HH Yu, H Bonates, TO Gulabani, V Azok, J Hoehn, G Hammer, PL Baird, AE Li, KC AF Reddy, Anupama Wang, Honghui Yu, Hua Bonates, Tiberius O. Gulabani, Vimla Azok, Joseph Hoehn, Gerard Hammer, Peter L. Baird, Alison E. Li, King C. TI Logical Analysis of Data (LAD) model for the early diagnosis of acute ischemic stroke SO BMC MEDICAL INFORMATICS AND DECISION MAKING LA English DT Article ID OVARIAN-CANCER; SERUM; PATTERNS; PREDICTION; ALGORITHM; RISK AB Background: Strokes are a leading cause of morbidity and the first cause of adult disability in the United States. Currently, no biomarkers are being used clinically to diagnose acute ischemic stroke. A diagnostic test using a blood sample from a patient would potentially be beneficial in treating the disease. Results: A classification approach is described for differentiating between proteomic samples of stroke patients and controls, and a second novel predictive model is developed for predicting the severity of stroke as measured by the National Institutes of Health Stroke Scale (NIHSS). The models were constructed by applying the Logical Analysis of Data ( LAD) methodology to the mass peak profiles of 48 stroke patients and 32 controls. The classification model was shown to have an accuracy of 75% when tested on an independent validation set of 35 stroke patients and 25 controls, while the predictive model exhibited superior performance when compared to alternative algorithms. In spite of their high accuracy, both models are extremely simple and were developed using a common set consisting of only 3 peaks. Conclusion: We have successfully identified 3 biomarkers that can detect ischemic stroke with an accuracy of 75%. The performance of the classification model on the validation set and on cross-validation does not deteriorate significantly when compared to that on the training set, indicating the robustness of the model. As in the case of the LAD classification model, the results of the predictive model validate the function constructed on our support-set for approximating the severity scores of stroke patients. The correlation and root mean absolute error of the LAD predictive model are consistently superior to those of the other algorithms used ( Support vector machines, C4.5 decision trees, Logistic regression and Multilayer perceptron). C1 [Wang, Honghui; Azok, Joseph; Li, King C.] Natl Inst Hlth, Mol Imaging Lab, Ctr Clin, Bethesda, MD 20892 USA. [Reddy, Anupama; Bonates, Tiberius O.; Gulabani, Vimla; Hammer, Peter L.] RUTCOR, Rutgers Ctr Operat Res, Piscataway, NJ 08854 USA. [Yu, Hua; Baird, Alison E.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA. [Wang, Honghui; Hoehn, Gerard] Natl Inst Hlth, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Li, King C.] Methodist Hosp, Dept Radiol, Houston, TX 77030 USA. RP Li, KC (reprint author), Natl Inst Hlth, Mol Imaging Lab, Ctr Clin, Bethesda, MD 20892 USA. EM areddy@rutcor.rutgers.edu; hwang2@cc.nih.gov; Hua.Yu@downstate.edu; tbonates@rutcor.rutgers.edu; vgulabani@rutcor.rutgers.edu; Jazok@cc.nih.gov; gerry.hoehn@tevaneuro.com; hammer@rutcor.rutgers.edu; Alison.baird@downstate.edu; kli@tmh.tmc.edu RI Bonates, Tiberius/I-5404-2012 OI Bonates, Tiberius/0000-0002-3991-1296 FU Intramural NIH HHS NR 21 TC 8 Z9 8 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6947 J9 BMC MED INFORM DECIS JI BMC Med. Inform. Decis. Mak. PD JUL 10 PY 2008 VL 8 AR 30 DI 10.1186/1472-6947-8-30 PG 13 WC Medical Informatics SC Medical Informatics GA 335OW UT WOS:000258300900001 PM 18616825 ER PT J AU Valdez, CA Saavedra, JE Showalter, BM Davies, KM Wilde, TC Citro, ML Barchi, JJ Deschamps, JR Parrish, D El-Gayar, S Schleicher, U Bogdan, C Keefer, LK AF Valdez, Carlos A. Saavedra, Joseph E. Showalter, Brett M. Davies, Keith M. Wilde, Thomas C. Citro, Michael L. Barchi, Joseph J., Jr. Deschamps, Jeffrey R. Parrish, Damon El-Gayar, Stefan Schleicher, Ulrike Bogdan, Christian Keefer, Larry K. TI Hydrolytic reactivity trends among potential prodrugs of the O(2)-glycosylated diazeniumdiolate family. Targeting nitric oxide to macrophages for antileishmanial activity SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID NECROSIS-FACTOR-ALPHA; LEISHMANIA-MAJOR AMASTIGOTES; DEPENDENT KILLING MECHANISM; GROWTH-FACTOR-BETA; IFN-GAMMA; MANNOSE RECEPTOR; HOST MACROPHAGES; SYNTHASE; SUPPRESSION; ACTIVATION AB Glycosylated diazeniumdiolates of structure R(2)NN(O)=NO-R' (R' = a saccharide residue) are potential prodrugs of the nitric oxide (NO)-releasing but acid-sensitive R(2)NN(O)=NO(-) ion. Moreover, cleaving the acid-stable glycosides under alkaline conditions provides a convenient protecting group strategy for diazeniumdiolate ions. Here, we report comparative hydrolysis rate data for five representative glycosylated diazeniumdiolates at pH 14, 7.4, and 3.8-4.6 as background for further developing both the protecting group application and the ability to target NO pharmacologically to macrophages harboring intracellular pathogens. Confirming the potential in the latter application, adding R(2)NN(O)=NO-GlcNAc (where R(2)N = diethylamino or pyrrolidin-1-yl and GlcNAc = N-acetylglucosamin-1-yl) to cultures of infected mouse macrophages that were deficient in inducible NO synthase caused rapid death of the intracellular protozoan parasite Leishmania major with no host cell toxicity. C1 [Valdez, Carlos A.; Showalter, Brett M.; Wilde, Thomas C.; Keefer, Larry K.] NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. [Saavedra, Joseph E.; Citro, Michael L.] NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21702 USA. [Davies, Keith M.] George Mason Univ, Dept Chem, Fairfax, VA 22030 USA. [Barchi, Joseph J., Jr.] NCI, Med Chem Lab, Frederick, MD 21702 USA. [Deschamps, Jeffrey R.; Parrish, Damon] USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA. [El-Gayar, Stefan; Schleicher, Ulrike; Bogdan, Christian] Univ Klinikum Erlangen, Mikrobiol Inst Klin Mikrobiol Immunol & Hyg, D-91054 Erlangen, Germany. [Schleicher, Ulrike; Bogdan, Christian] Univ Freiburg Klinikum, Abt Mikrobiol & Hyg, Inst Med Mikrobiol & Hyg, D-79104 Freiburg, Germany. RP Keefer, LK (reprint author), NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. EM keefer@ncifcrf.gov RI Barchi Jr., Joseph/N-3784-2014; Keefer, Larry/N-3247-2014; OI Keefer, Larry/0000-0001-7489-9555; Deschamps, Jeffrey/0000-0001-5845-0010 FU Intramural NIH HHS; NCI NIH HHS [N01 CO012400, N01-CO-12400, N01CO12400]; NIDA NIH HHS [Y01 DA006002, Y1-DA6002] NR 37 TC 20 Z9 20 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUL 10 PY 2008 VL 51 IS 13 BP 3961 EP 3970 DI 10.1021/jm8000482 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 322QS UT WOS:000257391000030 PM 18533711 ER PT J AU Shaffer, AL Emre, NCT Lamy, L Ngo, VN Wright, G Xiao, WM Powell, J Dave, S Yu, X Zhao, H Zeng, YX Chen, BZ Epstein, J Staudt, LM AF Shaffer, Arthur L. Emre, N. C. Tolga Lamy, Laurence Ngo, Vu N. Wright, George Xiao, Wenming Powell, John Dave, Sandeep Yu, Xin Zhao, Hong Zeng, Yuxin Chen, Bangzheng Epstein, Joshua Staudt, Louis M. TI IRF4 addiction in multiple myeloma SO NATURE LA English DT Article ID PLASMA-CELL DIFFERENTIATION; LYMPHOMA-CELLS; MYC; EXPRESSION; CANCER; ACTIVATION; PROFILES; SURVIVAL AB The transcription factor IRF4 ( interferon regulatory factor 4) is required during an immune response for lymphocyte activation and the generation of immunoglobulin- secreting plasma cells(1-3). Multiple myeloma, a malignancy of plasma cells, has a complex molecular aetiology with several subgroups defined by gene expression profiling and recurrent chromosomal translocations(4,5). Moreover, the malignant clone can sustain multiple oncogenic lesions, accumulating genetic damage as the disease progresses(6,7). Current therapies for myeloma can extend survival but are not curative(8,9). Hence, new therapeutic strategies are needed that target molecular pathways shared by all subtypes of myeloma. Here we show, using a loss- of- function, RNA- interference- based genetic screen, that IRF4 inhibition is toxic to myeloma cell lines, regardless of transforming oncogenic mechanism. Gene expression profiling and genome- wide chromatin immunoprecipitation analysis uncovered an extensive network of IRF4 target genes and identified MYC as a direct target of IRF4 in activated B cells and myeloma. Unexpectedly, IRF4 was itself a direct target of MYC transactivation, generating an autoregulatory circuit in myeloma cells. Although IRF4 is not genetically altered in most myelomas, they are nonetheless addicted to an aberrant IRF4 regulatory network that fuses the gene expression programmes of normal plasma cells and activated B cells. C1 [Shaffer, Arthur L.; Emre, N. C. Tolga; Lamy, Laurence; Ngo, Vu N.; Dave, Sandeep; Yu, Xin; Zhao, Hong; Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Wright, George] NCI, Biometr Res Branch, Rockville, MD 20892 USA. [Xiao, Wenming; Powell, John] NIH, Bioinformat & Mol Anal Sect, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. [Zeng, Yuxin; Chen, Bangzheng; Epstein, Joshua] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72212 USA. RP Staudt, LM (reprint author), NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM lstaudt@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [R01 CA113992-02, CA113992, CA97513, R01 CA113992, R33 CA097513-03] NR 29 TC 261 Z9 270 U1 4 U2 21 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUL 10 PY 2008 VL 454 IS 7201 BP 226 EP 231 DI 10.1038/nature07064 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 323RU UT WOS:000257466900046 PM 18568025 ER PT J AU Kumwenda, NI Hoover, DR Mofenson, LM Thigpen, MC Kafulafula, G Li, Q Mipando, L Nkanaunena, K Mebrahtu, T Bulterys, M Fowler, MG Taha, TE AF Kumwenda, Newton I. Hoover, Donald R. Mofenson, Lynne M. Thigpen, Michael C. Kafulafula, George Li, Qing Mipando, Linda Nkanaunena, Kondwani Mebrahtu, Tsedal Bulterys, Marc Fowler, Mary Glenn Taha, Taha E. TI Extended antiretroviral prophylaxis to reduce breast-milk HIV-1 transmission SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MOTHER-TO-CHILD; RANDOMIZED-TRIAL; POSTEXPOSURE PROPHYLAXIS; WEST-AFRICA; ZIDOVUDINE; INFANTS; INTERRUPTION; REGIMENS; EFFICACY; THERAPY AB Background: Effective strategies are urgently needed to reduce mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) through breast-feeding in resource-limited settings. Methods: Women with HIV-1 infection who were breast-feeding infants were enrolled in a randomized, phase 3 trial in Blantyre, Malawi. At birth, the infants were randomly assigned to one of three regimens: single-dose nevirapine plus 1 week of zidovudine (control regimen) or the control regimen plus daily extended prophylaxis either with nevirapine (extended nevirapine) or with nevirapine plus zidovudine (extended dual prophylaxis) until the age of 14 weeks. Using Kaplan-Meier analyses, we assessed the risk of HIV-1 infection among infants who were HIV-1-negative on DNA polymerase-chain-reaction assay at birth. Results: Among 3016 infants in the study, the control group had consistently higher rates of HIV-1 infection from the age of 6 weeks through 18 months. At 9 months, the estimated rate of HIV-1 infection (the primary end point) was 10.6% in the control group, as compared with 5.2% in the extended-nevirapine group (P<0.001) and 6.4% in the extended-dual-prophylaxis group (P=0.002). There were no significant differences between the two extended-prophylaxis groups. The frequency of breast-feeding did not differ significantly among the study groups. Infants receiving extended dual prophylaxis had a significant increase in the number of adverse events (primarily neutropenia) that were deemed to be possibly related to a study drug. Conclusions: Extended prophylaxis with nevirapine or with nevirapine and zidovudine for the first 14 weeks of life significantly reduced postnatal HIV-1 infection in 9-month-old infants. (ClinicalTrials.gov number, NCT00115648.). C1 [Kumwenda, Newton I.; Li, Qing; Mebrahtu, Tsedal; Taha, Taha E.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Fowler, Mary Glenn] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. [Hoover, Donald R.] Rutgers State Univ, Piscataway, NJ USA. [Mofenson, Lynne M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Thigpen, Michael C.; Bulterys, Marc] Ctr Dis Control & Prevent, Atlanta, GA USA. [Kafulafula, George] Univ Malawi, Coll Med, Blantyre, Malawi. [Mipando, Linda; Nkanaunena, Kondwani] Johns Hopkins Univ Coll Med Res Project, Blantyre, Malawi. RP Taha, TE (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Rm E7138,615 N Wolfe St, Baltimore, MD 21205 USA. EM ttaha@jhsph.edu OI Mofenson, Lynne/0000-0002-2818-9808 FU NCHHSTP CDC HHS [5-U50-PS022061-05]; ODCDC CDC HHS [U50-CC0222061] NR 23 TC 234 Z9 238 U1 2 U2 9 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 10 PY 2008 VL 359 IS 2 BP 119 EP 129 DI 10.1056/NEJMoa0801941 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 323PJ UT WOS:000257459000003 PM 18525035 ER PT J AU Guerci, AD Bild, DE Kronmal, RA AF Guerci, Alan D. Bild, Diane E. Kronmal, Richard A. TI Coronary calcium and events in four ethnic groups - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Guerci, Alan D.] St Francis Hosp, Roslyn, NY 11576 USA. [Bild, Diane E.] NHLBI, Bethesda, MD 20892 USA. [Kronmal, Richard A.] Univ Washington, Seattle, WA 98195 USA. RP Guerci, AD (reprint author), St Francis Hosp, Roslyn, NY 11576 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 10 PY 2008 VL 359 IS 2 BP 204 EP 204 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 323PJ UT WOS:000257459000023 ER PT J AU Churbanov, A Winters-Hilt, S Koonin, EV Rogozin, IB AF Churbanov, Alexander Winters-Hilt, Stephen Koonin, Eugene V. Rogozin, Igor B. TI Accumulation of GC donor splice signals in mammals SO BIOLOGY DIRECT LA English DT Article ID GENOME; SITES; POSITIONS; SEQUENCES AB The GT dinucleotide in the first two intron positions is the most conserved element of the U2 donor splice signals. However, in a small fraction of donor sites, GT is replaced by GC. A substantial enrichment of GC in donor sites of alternatively spliced genes has been observed previously in human, nematode and Arabidopsis, suggesting that GC signals are important for regulation of alternative splicing. We used parsimony analysis to reconstruct evolution of donor splice sites and inferred 298 GT > GC conversion events compared to 40 GC > GT conversion events in primate and rodent genomes. Thus, there was substantive accumulation of GC donor splice sites during the evolution of mammals. Accumulation of GC sites might have been driven by selection for alternative splicing. Reviewers: This article was reviewed by Jerzy Jurka and Anton Nekrutenko. For the full reviews, please go to the Reviewers' Reports section. C1 [Koonin, Eugene V.; Rogozin, Igor B.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. [Churbanov, Alexander] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Winters-Hilt, Stephen] Univ New Orleans, Dept Comp Sci, New Orleans, LA 70148 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM atchourbanov@lumc.edu; winters@cs.uno.edu; koonin@ncbi.nlm.nih.gov; rogozin@ncbi.nlm.nih.gov FU Intramural NIH HHS; NLM NIH HHS [K22 LM008794, K22LM008794] NR 19 TC 11 Z9 12 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD JUL 9 PY 2008 VL 3 BP 1 EP 4 AR 30 DI 10.1186/1745-6150-3-30 PG 4 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 333XJ UT WOS:000258186600001 PM 18613975 ER PT J AU Ix, JH Wassel, CL Kanaya, AM Vittinghoff, E Johnson, KC Koster, A Cauley, JA Harris, TB Cummings, SR Shlipak, MG AF Ix, Joachim H. Wassel, Christina L. Kanaya, Alka M. Vittinghoff, Eric Johnson, Karen C. Koster, Annemarie Cauley, Jane A. Harris, Tamara B. Cummings, Steven R. Shlipak, Michael G. CA Hlth ABC Study TI Fetuin-A and incident diabetes mellitus in older persons SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ALPHA(2)-HEREMANS-SCHMID GLYCOPROTEIN/FETUIN-A; PLASMINOGEN-ACTIVATOR INHIBITOR-1; RECEPTOR TYROSINE KINASE; CHRONIC KIDNEY-DISEASE; CASE-COHORT DESIGNS; INSULIN-RESISTANCE; METABOLIC SYNDROME; DIALYSIS PATIENTS; ASSOCIATION; SERUM AB Context Fetuin-A is a hepatic secretory protein that binds the insulin receptor and inhibits insulin action in vitro. In prior cross- sectional studies in humans, higher fetuin-A levels were associated with insulin resistance. However, the longitudinal association of fetuin- A with incident type 2 diabetes mellitus is unknown. Objective To determine whether fetuin- A levels are associated with incident diabetes in older persons. Design, Setting, and Participants Observational study among 3075 well-functioning persons aged 70 to 79 years. In this case- cohort study, we retrospectively measured fetuin- A levels in baseline serum among 406 randomly selected participants without prevalent diabetes, and all participants who developed incident diabetes mellitus during a 6- year follow- up ( to August 31, 2005). Main Outcome Measure Incident diabetes mellitus. Results Incident diabetes developed in 135 participants ( 10.1 cases/ 1000 person-years). Participants with fetuin- A levels within the highest tertile ( > 0.97 g/ L) had an increased risk of incident diabetes ( 13.3 cases/ 1000 person- years) compared with participants in the lowest tertile ( <= 0.76 g/ L) ( 6.5 cases/ 1000 person- years) in models adjusted for age, sex, race, waist circumference, body weight, physical activity, blood pressure level, fasting glucose level, high- density lipoprotein cholesterol concentration, triglyceride concentration, and C- reactive protein level ( adjusted hazard ratio, 2.41; 95% confidence interval, 1.28- 4.53; P=. 007). The association was not affected by adipocytokine levels but was moderately attenuated by adjustment for visceral adiposity ( adjusted hazard ratio of highest vs lowest tertile 1.72; 95% confidence interval, 0.98- 3.05; P=. 06). Conclusion Among well- functioning older persons, serum fetuin- A is associated with incident diabetes, independent of other markers of insulin resistance. C1 [Ix, Joachim H.] Univ Calif San Diego, Dept Med, Div Nephrol & Hypertens, San Diego, CA 92161 USA. [Ix, Joachim H.] Univ Calif San Diego, Dept Family & Prevent Med, Div Prevent Med, San Diego, CA 92161 USA. [Ix, Joachim H.] San Diego Vet Affairs Healthcare Syst, San Diego, CA 92161 USA. [Wassel, Christina L.] Univ Minnesota, Dept Epidemiol, Minneapolis, MN USA. [Wassel, Christina L.; Vittinghoff, Eric; Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Kanaya, Alka M.; Cummings, Steven R.; Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Johnson, Karen C.] Univ Tennessee, Ctr Hlth Sci, Dept Med, Memphis, TN 38163 USA. [Koster, Annemarie; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Cauley, Jane A.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Cummings, Steven R.] Calif Pacific Med Ctr, Dept Med, San Francisco, CA USA. [Cummings, Steven R.] San Francisco Coordinating Ctr, San Francisco, CA USA. [Shlipak, Michael G.] Vet Affairs Med Ctr, San Francisco, CA 94121 USA. RP Ix, JH (reprint author), Univ Calif San Diego, Dept Med, Div Nephrol & Hypertens, 3350 La Jolla Village Dr,Mail Code 111-H, San Diego, CA 92161 USA. EM joeix@ucsd.edu RI Koster, Annemarie/E-7438-2010; Newman, Anne/C-6408-2013; Cauley, Jane/N-4836-2015 OI Newman, Anne/0000-0002-0106-1150; Cauley, Jane/0000-0003-0752-4408 FU Intramural NIH HHS [Z01 AG007390-02]; NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] NR 46 TC 139 Z9 139 U1 0 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 9 PY 2008 VL 300 IS 2 BP 182 EP 188 DI 10.1001/jama.300.2.182 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 323GV UT WOS:000257435500022 PM 18612115 ER PT J AU Gerfen, CR Paletzki, R Worley, P AF Gerfen, Charles R. Paletzki, Ronald Worley, Paul TI Differences between dorsal and ventral striatum in Drd1a dopamine receptor coupling of dopamine- and cAMP-regulated phosphoprotein-32 to activation of extracellular signal-regulated kinase SO JOURNAL OF NEUROSCIENCE LA English DT Article DE amphetamine; basal ganglia; D(1); dopamine; dopamine receptor; drug abuse; Parkinson's disease; striatum ID CASCADE; REWARD; MECHANISMS; ADDICTION; ERK AB Dopamine receptor signaling exhibits prominent plasticity that is important for the pathogenesis of both addictive and movement disorders. Psychoactive stimulants that activate the dopamine D(1) receptor (Drd1a) induce the rapid phosphorylation and activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in neurons of the nucleus accumbens and ventral striatum. This response is known to be dependent on the phosphatase inhibitor dopamine- and cAMP-regulated phosphoprotein-32 (DARPP-32) and appears critical for the sensitization of Drd1a responses that contributes to addiction. Loss of dopamine input to the striatum, as in models of Parkinson's disease (PD), also results in a sensitization of responses to dopamine agonists that is manifest by increased activation of ERK1/2 in the dorsal striatum. Here, we test whether DARPP-32 is required for sensitization of Drd1a responses in a PD model. In the normal dorsal striatum, there is minimal Drd1a-mediated activation of ERK1/2; however, in the PD model there is robust Drd1a-mediated activation of ERK1/2. In both wild-type and DARPP-32 knock-out mice, Drd1a robustly induces pERK1/2 throughout the dopamine- depleted striatum. These findings indicate that Drd1a sensitization relevant for PD occurs by a novel mechanism that does not require DARPP-32. C1 [Gerfen, Charles R.; Paletzki, Ronald] NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. [Worley, Paul] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Gerfen, CR (reprint author), Natl Inst Hlth Anim Ctr, Bldg 111, Dickerson, MD 20842 USA. EM gerfenc@mail.nih.gov FU Intramural NIH HHS [Z01 MH002497-18, Z99 MH999999]; NIDA NIH HHS [DA11742, R01 DA011742, R01 DA011742-08, R37 DA010309] NR 18 TC 44 Z9 44 U1 0 U2 8 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 9 PY 2008 VL 28 IS 28 BP 7113 EP 7120 DI 10.1523/JNEUROSCI.3952-07.2008 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 323TT UT WOS:000257472000012 PM 18614680 ER PT J AU Isoda, M Hikosaka, O AF Isoda, Masaki Hikosaka, Okihide TI Role for subthalamic nucleus neurons in switching from automatic to controlled eye movement SO JOURNAL OF NEUROSCIENCE LA English DT Article DE subthalamic nucleus; basal ganglia; monkeys; saccades; habitual action; conscious control ID MEDIAL FRONTAL-CORTEX; SUPPLEMENTARY MOTOR AREA; BASAL GANGLIA; SUBSTANTIA-NIGRA; DOPAMINERGIC INNERVATION; OCULOMOTOR FUNCTIONS; SUPERIOR COLLICULUS; MONKEY; PARKINSONISM; ORGANIZATION AB The subthalamic nucleus (STN) of the basal ganglia is an important element of motor control. This is demonstrated by involuntary movements induced by STN lesions and the successful treatment of Parkinson's disease by STN stimulation. However, it is still unclear how individual STN neurons participate in motor control. Here, we report that the STN has a function in switching from automatic to volitionally controlled eye movement. In the STN of trained macaque monkeys, we found neurons that showed a phasic change in activity specifically before volitionally controlled saccades which were switched from automatic saccades. A majority of switch-related neurons were considered to inhibit no-longer-valid automatic processes, and the inhibition started early enough to enable the animal to switch. We suggest that the STN mediates the control signal originated from the medial frontal cortex and implements the behavioral switching function using its connections with other basal ganglia nuclei and the superior colliculus. C1 [Isoda, Masaki] RIKEN, Brain Sci Inst, Lab Symbol Cognit Dev, Wako, Saitama 3510198, Japan. [Isoda, Masaki; Hikosaka, Okihide] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Isoda, M (reprint author), RIKEN, Brain Sci Inst, Lab Symbol Cognit Dev, 2-1 Hirosawa, Wako, Saitama 3510198, Japan. EM isodam@brain.riken.jp FU Intramural NIH HHS [Z01 EY000415-05] NR 50 TC 134 Z9 136 U1 1 U2 11 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 9 PY 2008 VL 28 IS 28 BP 7209 EP 7218 DI 10.1523/JNEUROSCI.0487-08.2008 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 323TT UT WOS:000257472000023 PM 18614691 ER PT J AU Kronenberg, G Harms, C Sobol, RW Cardozo-Pelaez, F Linhart, H Winter, B Balkaya, M Gertz, K Gay, SB Cox, D Eckart, S Ahmadi, M Juckel, G Kempermann, G Hellweg, R Sohr, R Hortnagl, H Wilson, SH Jaenisch, R Endres, M AF Kronenberg, Golo Harms, Christoph Sobol, Robert W. Cardozo-Pelaez, Fernando Linhart, Heinz Winter, Benjamin Balkaya, Mustafa Gertz, Karen Gay, Shanna B. Cox, David Eckart, Sarah Ahmadi, Michael Juckel, Georg Kempermann, Gerd Hellweg, Rainer Sohr, Reinhard Hoertnagl, Heide Wilson, Samuel H. Jaenisch, Rudolf Endres, Matthias TI Folate deficiency induces neurodegeneration and brain dysfunction in mice lacking uracil DNA glycosylase SO JOURNAL OF NEUROSCIENCE LA English DT Review DE neurodegeneration; memory impairment; despair; folate deficiency; base excision repair; neurogenesis ID NEURAL-TUBE DEFECTS; ADULT HIPPOCAMPAL NEUROGENESIS; MAJOR DEPRESSIVE DISORDER; OXYGEN SPECIES PRODUCTION; MILD CEREBRAL-ISCHEMIA; FOLIC-ACID DEFICIENCY; NEURONAL CELL-DEATH; MITOCHONDRIAL-DNA; ALZHEIMERS-DISEASE; DENTATE GYRUS AB Folate deficiency and resultant increased homocysteine levels have been linked experimentally and epidemiologically with neurodegenerative conditions like stroke and dementia. Moreover, folate deficiency has been implicated in the pathogenesis of psychiatric disorders, most notably depression. We hypothesized that the pathogenic mechanisms include uracil misincorporation and, therefore, analyzed the effects of folate deficiency in mice lacking uracil DNA glycosylase (Ung(-/-)) versus wild-type controls. Folate depletion increased nuclear mutation rates in Ung(-/-) embryonic fibroblasts, and conferred death of cultured Ung(-/-) hippocampal neurons. Feeding animals a folate-deficient diet (FD) for 3 months induced degeneration of CA3 pyramidal neurons in Ung(-/-) but not Ung(-/-) mice along with decreased hippocampal expression of brain-derived neurotrophic factor protein and decreased brain levels of antioxidant glutathione. Furthermore, FD induced cognitive deficits and mood alterations such as anxious and despair-like behaviors that were aggravated in Ung(-/-) mice. Independent of Ung genotype, FD increased plasma homocysteine levels, altered brain monoamine metabolism, and inhibited adult hippocampal neurogenesis. These results indicate that impaired uracil repair is involved in neurodegeneration and neuropsychiatric dysfunction induced by experimental folate deficiency. C1 [Kronenberg, Golo; Harms, Christoph; Winter, Benjamin; Balkaya, Mustafa; Gertz, Karen; Ahmadi, Michael; Kempermann, Gerd; Endres, Matthias] Charite Univ Med Berlin, Neurol Klin & Poliklin, D-10117 Berlin, Germany. [Kronenberg, Golo; Endres, Matthias] Charite Univ Med Berlin, Ctr Stroke Res, D-10117 Berlin, Germany. [Sohr, Reinhard; Hoertnagl, Heide] Charite Univ Med Berlin, Inst Pharmakol & Toxikol, D-10117 Berlin, Germany. [Kronenberg, Golo; Eckart, Sarah; Hellweg, Rainer] Charite Univ Med Berlin, Klin & Hsch Ambulanz Psychiat & Psychotherapie, D-14050 Berlin, Germany. [Sobol, Robert W.] Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15212 USA. [Sobol, Robert W.; Gay, Shanna B.] Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Pittsburgh, PA 15212 USA. [Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC USA. [Cardozo-Pelaez, Fernando; Cox, David] Univ Montana, Dept Biomed & Pharmaceut Sci, Environm Hlth Sci Ctr, Missoula, MT 59812 USA. [Linhart, Heinz; Jaenisch, Rudolf] MIT, Whitehead Inst, Cambridge, MA 02142 USA. [Juckel, Georg] Ruhr Univ Bochum, Westfal Zentrum, D-44791 Bochum, Germany. [Kempermann, Gerd] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany. RP Endres, M (reprint author), Charite Univ Med Berlin, Neurol Klin & Poliklin, Campus Mitte,Charitepl 1, D-10117 Berlin, Germany. EM matthias.endres@charite.de RI Kempermann, Gerd/F-5416-2010; Sobol, Robert/E-4125-2013; Kronenberg, Golo/F-8772-2010; Gertz, Karen/J-1603-2015; OI Kempermann, Gerd/0000-0002-5304-4061; Sobol, Robert/0000-0001-7385-3563; Harms, Christoph/0000-0002-2063-2860 FU Intramural NIH HHS; NCI NIH HHS [P20 CA103730]; NCRR NIH HHS [P20 RR015583, P20 RR017670, P20RR015583-07, P20RR017670-04]; NIA NIH HHS [101 AG24364-01, 1R15AG023604-01, R01 AG024364, R15 AG023604]; NIEHS NIH HHS [R13 ES016721, R13 ES016721-01] NR 103 TC 34 Z9 36 U1 1 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 9 PY 2008 VL 28 IS 28 BP 7219 EP 7230 DI 10.1523/JNEUROSCI.0940-08.2008 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 323TT UT WOS:000257472000024 PM 18614692 ER PT J AU Chiang, YJ Hsiao, SJ Yver, D Cushman, SW Tessarollo, L Smith, S Hodes, RJ AF Chiang, Y. Jeffrey Hsiao, Susan J. Yver, Dena Cushman, Samuel W. Tessarollo, Lino Smith, Susan Hodes, Richard J. TI Tankyrase 1 and Tankyrase 2 Are Essential but Redundant for Mouse Embryonic Development SO PLOS ONE LA English DT Article AB Tankyrases are proteins with poly(ADP-ribose) polymerase activity. Human tankyrases post-translationally modify multiple proteins involved in processes including maintenance of telomere length, sister telomere association, and trafficking of glut4-containing vesicles. To date, however, little is known about in vivo functions for tankyrases. We recently reported that body size was significantly reduced in mice deficient for tankyrase 2, but that these mice otherwise appeared developmentally normal. In the present study, we report generation of tankyrase 1-deficient and tankyrase 1 and 2 double-deficient mice, and use of these mutant strains to systematically assess candidate functions of tankyrase 1 and tankyrase 2 in vivo. No defects were observed in development, telomere length maintenance, or cell cycle regulation in tankyrase 1 or tankyrase 2 knockout mice. In contrast to viability and normal development of mice singly deficient in either tankyrase, deficiency in both tankyrase 1 and tankyrase 2 results in embryonic lethality by day 10, indicating that there is substantial redundancy between tankyrase 1 and tankyrase 2, but that tankyrase function is essential for embryonic development. C1 [Chiang, Y. Jeffrey; Hodes, Richard J.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Tessarollo, Lino] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD USA. [Hsiao, Susan J.; Smith, Susan] NYU, Sch Med, Skirball Inst, Kimmel Ctr Biol & Med, New York, NY USA. [Yver, Dena; Cushman, Samuel W.] NIDDKD, NIH, Bethesda, MD USA. [Hodes, Richard J.] NIA, NIH, Bethesda, MD USA. RP Chiang, YJ (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM chiangj@mail.nih.gov OI Smith, Susan/0000-0002-8213-5915 FU NIH [GM07238, RO1 CA95099]; National Institutes of Health (NIH), National Cancer Institute FX S.J.H. was supported by the NIH Predoctoral Training Grant (GM07238). S.S. was supported by the NIH (RO1 CA95099). This research was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute. NR 30 TC 70 Z9 72 U1 1 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUL 9 PY 2008 VL 3 IS 7 AR e2639 DI 10.1371/journal.pone.0002639 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 417GZ UT WOS:000264065800041 PM 18612384 ER PT J AU Sugui, JA Kim, HS Zarember, KA Chang, YC Gallin, JI Nierman, WC Kwon-Chung, KJ AF Sugui, Janyce A. Kim, H. Stanley Zarember, Kol A. Chang, Yun C. Gallin, John I. Nierman, Willian C. Kwon-Chung, Kyung J. TI Genes Differentially Expressed in Conidia and Hyphae of Aspergillus fumigatus upon Exposure to Human Neutrophils SO PLOS ONE LA English DT Article AB Background: Aspergillus fumigatus is the most common etiologic agent of invasive aspergillosis in immunocompromised patients. Several studies have addressed the mechanism involved in host defense but only few have investigated the pathogen's response to attack by the host cells. To our knowledge, this is the first study that investigates the genes differentially expressed in conidia vs hyphae of A. fumigatus in response to neutrophils from healthy donors as well as from those with chronic granulomatous disease (CGD) which are defective in the production of reactive oxygen species. Methodology/Principal Findings: Transcriptional profiles of conidia and hyphae exposed to neutrophils, either from normal donors or from CGD patients, were obtained by using the genome-wide microarray. Upon exposure to either normal or CGD neutrophils, 244 genes were up-regulated in conidia but not in hyphae. Several of these genes are involved in the degradation of fatty acids, peroxisome function and the glyoxylate cycle which suggests that conidia exposed to neutrophils reprogram their metabolism to adjust to the host environment. In addition, the mRNA levels of four genes encoding proteins putatively involved in iron/copper assimilation were found to be higher in conidia and hyphae exposed to normal neutrophils compared to those exposed to CGD neutrophils. Deletants in several of the differentially expressed genes showed phenotypes related to the proposed functions, i.e. deletants of genes involved in fatty acid catabolism showed defective growth on fatty acids and the deletants of iron/copper assimilation showed higher sensitivity to the oxidative agent menadione. None of these deletants, however, showed reduced resistance to neutrophil attack. Conclusion: This work reveals the complex response of the fungus to leukocytes, one of the major host factors involved in antifungal defense, and identifies fungal genes that may be involved in establishing or prolonging infections in humans. C1 [Sugui, Janyce A.; Chang, Yun C.; Kwon-Chung, Kyung J.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Kim, H. Stanley] Korea Univ, Coll Med, Dept Med, Seoul, South Korea. [Zarember, Kol A.; Gallin, John I.] NIAID, Lab Host Defenses, NIH, Bethesda, MD USA. [Nierman, Willian C.] J Craig Venter Inst, Rockville, MD USA. RP Sugui, JA (reprint author), NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM june_kwon-chung@nih.gov FU Clinical Center of the National Institutes of Health; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD FX This study was supported by funds from the Clinical Center of the National Institutes of Health and the intramural program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD. NR 53 TC 52 Z9 313 U1 0 U2 17 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUL 9 PY 2008 VL 3 IS 7 AR e2655 DI 10.1371/journal.pone.0002655 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 417GZ UT WOS:000264065800057 PM 18648542 ER PT J AU Wu, YM Ellis, RD Shaffer, D Fontes, E Malkin, EM Mahanty, S Fay, MP Narum, D Rausch, K Miles, AP Aebig, J Orcutt, A Muratova, O Song, GH Lambert, L Zhu, DM Miura, K Long, C Saul, A Miller, LH Durbin, AP AF Wu, Yimin Ellis, Ruth D. Shaffer, Donna Fontes, Erica Malkin, Elissa M. Mahanty, Siddhartha Fay, Michael P. Narum, David Rausch, Kelly Miles, Aaron P. Aebig, Joan Orcutt, Andrew Muratova, Olga Song, Guanhong Lambert, Lynn Zhu, Daming Miura, Kazutoyo Long, Carole Saul, Allan Miller, Louis H. Durbin, Anna P. TI Phase 1 Trial of Malaria Transmission Blocking Vaccine Candidates Pfs25 and Pvs25 Formulated with Montanide ISA 51 SO PLOS ONE LA English DT Article AB Background: Pfs25 and Pvs25, surface proteins of mosquito stage of the malaria parasites P. falciparum and P. vivax, respectively, are leading candidates for vaccines preventing malaria transmission by mosquitoes. This single blinded, dose escalating, controlled Phase 1 study assessed the safety and immunogenicity of recombinant Pfs25 and Pvs25 formulated with Montanide ISA 51, a water-in-oil emulsion. Methodology/Principal Findings: The trial was conducted at The Johns Hopkins Center for Immunization Research, Washington DC, USA, between May 16, 2005-April 30, 2007. The trial was designed to enroll 72 healthy male and nonpregnant female volunteers into 1 group to receive adjuvant control and 6 groups to receive escalating doses of the vaccines. Due to unexpected reactogenicity, the vaccination was halted and only 36 volunteers were enrolled into 4 groups: 3 groups of 10 volunteers each were immunized with 5 mu g of Pfs25/ISA 51, 5 mu g of Pvs25/ISA 51, or 20 mu g of Pvs25/ISA 51, respectively. A fourth group of 6 volunteers received adjuvant control (PBS/ISA 51). Frequent local reactogenicity was observed. Systemic adverse events included two cases of erythema nodosum considered to be probably related to the combination of the antigen and the adjuvant. Significant antibody responses were detected in volunteers who completed the lowest scheduled doses of Pfs25/ISA 51. Serum anti-Pfs25 levels correlated with transmission blocking activity. Conclusion/Significance: It is feasible to induce transmission blocking immunity in humans using the Pfs25/ISA 51 vaccine, but these vaccines are unexpectedly reactogenic for further development. This is the first report that the formulation is associated with systemic adverse events including erythema nodosum. C1 [Wu, Yimin; Ellis, Ruth D.; Malkin, Elissa M.; Mahanty, Siddhartha; Narum, David; Rausch, Kelly; Miles, Aaron P.; Aebig, Joan; Orcutt, Andrew; Muratova, Olga; Song, Guanhong; Lambert, Lynn; Zhu, Daming; Miura, Kazutoyo; Long, Carole; Saul, Allan; Miller, Louis H.] NIAID, Malaria Vaccine Dev Branch, Rockville, MD USA. [Shaffer, Donna; Fontes, Erica; Durbin, Anna P.] Johns Hopkins Bloomberg, Sch Publ Hlth, Dept Int Hlth, Ctr Immunizat Res, Baltimore, MD USA. [Fay, Michael P.] NIAID, Biostat Res Branch, Bethesda, MD USA. RP Wu, YM (reprint author), NIAID, Malaria Vaccine Dev Branch, Rockville, MD USA. EM yiwu@niaid.nih.gov; adurbin@jhsph.edu RI Saul, Allan/I-6968-2013; OI Saul, Allan/0000-0003-0665-4091; Fay, Michael P./0000-0002-8643-9625; Mahanty, Siddhartha/0000-0003-1068-0524 FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health FX The study was funded by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. The funder played no role in study design, data collection and analysis, and manuscript preparation and submission. NR 35 TC 104 Z9 117 U1 0 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUL 9 PY 2008 VL 3 IS 7 AR e2636 DI 10.1371/journal.pone.0002636 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 417GZ UT WOS:000264065800038 PM 18612426 ER PT J AU Yamaza, T Miura, Y Bi, YM Liu, YZ Akiyama, K Sonoyama, W Patel, V Gutkind, S Young, M Gronthos, S Le, A Wang, CY Chen, WJ Shi, ST AF Yamaza, Takayoshi Miura, Yasuo Bi, Yanming Liu, Yongzhong Akiyama, Kentaro Sonoyama, Wataru Patel, Voymesh Gutkind, Silvio Young, Marian Gronthos, Stan Le, Anh Wang, Cun-Yu Chen, WanJun Shi, Songtao TI Pharmacologic Stem Cell Based Intervention as a New Approach to Osteoporosis Treatment in Rodents SO PLOS ONE LA English DT Article AB Background: Osteoporosis is the most prevalent skeletal disorder, characterized by a low bone mineral density (BMD) and bone structural deterioration, leading to bone fragility fractures. Accelerated bone resorption by osteoclasts has been established as a principal mechanism in osteoporosis. However, recent experimental evidences suggest that inappropriate apoptosis of osteoblasts/osteocytes accounts for, at least in part, the imbalance in bone remodeling as occurs in osteoporosis. The aim of this study is to examine whether aspirin, which has been reported as an effective drug improving bone mineral density in human epidemiology studies, regulates the balance between bone resorption and bone formation at stem cell levels. Methods and Findings: We found that T cell-mediated bone marrow mesenchymal stem cell (BMMSC) impairment plays a crucial role in ovariectomized-induced osteoporosis. Ex vivo mechanistic studies revealed that T cell-mediated BMMSC impairment was mainly attributed to the apoptosis of BMMSCs via the Fas/Fas ligand pathway. To explore potential of using pharmacologic stem cell based intervention as an approach for osteoporosis treatment, we selected ovariectomy (OVX)-induced ostoeporosis mouse model to examine feasibility and mechanism of aspirin-mediated therapy for osteoporosis. We found that aspirin can inhibit T cell activation and Fas ligand induced BMMSC apoptosis in vitro. Further, we revealed that aspirin increases osteogenesis of BMMSCs by aiming at telomerase activity and inhibits osteoclast activity in OVX mice, leading to ameliorating bone density. Conclusion: Our findings have revealed a novel osteoporosis mechanism in which activated T cells induce BMMSC apoptosis via Fas/Fas ligand pathway and suggested that pharmacologic stem cell based intervention by aspirin may be a new alternative in osteoporosis treatment including activated osteoblasts and inhibited osteoclasts. C1 [Yamaza, Takayoshi; Akiyama, Kentaro; Sonoyama, Wataru; Le, Anh; Shi, Songtao] Univ So Calif, Ctr Craniofacial Mol Biol, Sch Dent, Los Angeles, CA 90033 USA. [Miura, Yasuo] Kyoto Univ, Grad Sch Med, Kyoto, Japan. [Bi, Yanming; Liu, Yongzhong; Patel, Voymesh; Gutkind, Silvio; Young, Marian; Chen, WanJun] NIH, NIDCR, Bethesda, MD USA. [Gronthos, Stan] Inst Med & Vet Sci, Div Haematol, Mesenchymal Stem Cell Grp, Adelaide, SA, Australia. [Wang, Cun-Yu] Univ Calif Los Angeles, Sch Dent, Div Oral Biol & Med, Los Angeles, CA USA. RP Yamaza, T (reprint author), Univ So Calif, Ctr Craniofacial Mol Biol, Sch Dent, 2250 Alcazar St, Los Angeles, CA 90033 USA. EM wchen@mail.nih.gov; songtaos@usc.edu FU University of Southern California School of Dentistry; NIH [R01DE17449]; NIDCR FX This research was supported by University of Southern California School of Dentistry starting fund for S.S., an extramural grant from NIH (NIDCR R01DE17449 for S.S.), and NIDCR intramural fund. NR 40 TC 79 Z9 94 U1 0 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUL 9 PY 2008 VL 3 IS 7 AR e2615 DI 10.1371/journal.pone.0002615 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 417GZ UT WOS:000264065800017 PM 18612428 ER PT J AU Anderson, PAW Sleeper, LA Mahony, L Colan, SD Atz, AM Breitbart, RE Gersony, WM Gallagher, D Geva, T Margossian, R McCrindle, BW Paridon, S Schwartz, M Stylianou, M Williams, RV Clark, BJ AF Anderson, Page A. W. Sleeper, Lynn A. Mahony, Lynn Colan, Steven D. Atz, Andrew M. Breitbart, Roger E. Gersony, Welton M. Gallagher, Dianne Geva, Tal Margossian, Renee McCrindle, Brian W. Paridon, Stephen Schwartz, Marcy Stylianou, Mario Williams, Richard V. Clark, Bernard J., III CA Pediat Heart Network Investigat TI Contemporary outcomes after the Fontan procedure - A pediatric heart network multicenter study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID QUALITY-OF-LIFE; NATRIURETIC PEPTIDE; SINGLE VENTRICLE; HEALTH-STATUS; CHILDREN; ADOLESCENTS; ECHOCARDIOGRAPHY; OPERATION; EXERCISE; FAILURE AB Objectives We characterized a large cohort of children who had a Fontan procedure, with measures of functional health status, ventricular size and function, exercise capacity, heart rhythm, and brain natriuretic peptide (BNP). Background The characteristics of contemporary Fontan survivors are not well described. Methods We enrolled 546 children (age 6 to 18 years, mean 11.9 years) and compared them within pre-specified anatomic and procedure subgroups. History and outcome measures were obtained within a 3-month period. Results Predominant ventricular morphology was 49% left ventricular (LV), 34% right ventricular (RV), and 19% mixed. Ejection fraction (EF) was normal for 73% of subjects; diastolic function grade was normal for 28%. Child Health Questionnaire mean summary scores were lower than for control subjects; however, over 80% of subjects were in the normal range. Brain natriuretic peptide concentration ranged from < 4 to 652 pg/ml (median 13 pg/ml). Mean percent predicted peak O-2 consumption was 65% and decreased with age. Ejection fraction and EF Z score were lowest, and semilunar and atrioventricular (AV) valve regurgitation were more prevalent in the RV subgroup. Older age at Fontan was associated with more severe AV valve regurgitation. Most outcomes were not associated with a superior cavopulmonary connection before Fontan. Conclusions Measures of ventricular systolic function and functional health status, although lower on average in the cohort compared with control subjects, were in the majority of subjects within 2 standard deviations of the mean for control subjects. Right ventricular morphology was associated with poorer ventricular and valvular function. Effective strategies to preserve ventricular and valvular function, particularly for patients with RV morphology, are needed. C1 [Anderson, Page A. W.] Duke Univ, Med Ctr, Durham, NC 27710 USA. [Sleeper, Lynn A.; Gallagher, Dianne] New England Res Inst, Watertown, MA 02172 USA. [Mahony, Lynn] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Colan, Steven D.; Breitbart, Roger E.; Geva, Tal; Margossian, Renee; Schwartz, Marcy] Childrens Hosp, Boston, MA 02115 USA. [Atz, Andrew M.] Med Univ S Carolina, Charleston, SC 29425 USA. [Gersony, Welton M.] Columbia Univ, Med Ctr, New York, NY USA. [McCrindle, Brian W.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Paridon, Stephen; Clark, Bernard J., III] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Stylianou, Mario] NHLBI, Bethesda, MD 20892 USA. [Williams, Richard V.] Primary Childrens Med Ctr, Salt Lake City, UT 84103 USA. RP Anderson, PAW (reprint author), Duke Univ, Med Ctr, Res Pk Bldg 2,Room 113,Box 3218, Durham, NC 27710 USA. EM ander005@mc.duke.edu FU NHLBI NIH HHS [U01 HL068269, HL68270, HL68279, HL68281, HL68285, HL68288, HL68290, HL68292, U01 HL068270, U01 HL068279, U01 HL068281, U01 HL068285, U01 HL068288, U01 HL068290, U01 HL068292, U01 HL68269, U10 HL068270, U10 HL109778] NR 22 TC 179 Z9 183 U1 1 U2 7 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 JUL 8 PY 2008 VL 52 IS 2 BP 85 EP 98 DI 10.1016/j.jacc.2008.01.074 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 321FT UT WOS:000257290800001 PM 18598886 ER PT J AU Uetrecht, C Versluis, C Watts, NR Roos, WH Wuite, GJL Wingfield, PT Steven, AC Heck, AJR AF Uetrecht, Charlotte Versluis, Cees Watts, Norman R. Roos, Wouter H. Wuite, Gijs J. L. Wingfield, Paul T. Steven, Alasdair C. Heck, Albert J. R. TI High-resolution mass spectrometry of viral assemblies: Molecular composition and stability of dimorphic hepatitis B virus capsids SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE atomic force microscopy; collision-induced dissociation; macromolecular mass spectrometry; virus assembly; viral structural biology ID OF-FLIGHT INSTRUMENT; MACROMOLECULAR ASSEMBLIES; ELECTRON CRYOMICROSCOPY; PROTEIN COMPLEXES; MICROSCOPY; REVEALS; BIOLOGY AB Hepatitis B virus (HBV) is a major human pathogen. In addition to its importance in human health, there is growing interest in adapting HBV and other viruses for drug delivery and other nanotechnological applications. In both contexts, precise biophysical characterization of these large macromolecular particles is fundamental. HBV capsids are unusual in that they exhibit two distinct icosahedral geometries, nominally composed of 90 and 120 dimers with masses of approximate to 3 and approximate to 4 MDa, respectively. Here, a mass spectrometric approach was used to determine the masses of both capsids to within 0.1 %. It follows that both lattices are complete, consisting of exactly 180 and 240 subunits. Nanoindentation experiments by atomic-force microscopy indicate that both capsids have similar stabilities. The data yielded a Young's modulus of approximate to 0.4 GPa. This experimental approach, anchored on very precise and accurate mass measurements, appears to hold considerable potential for elucidating the assembly of viruses and other macromolecular particles. C1 [Uetrecht, Charlotte; Versluis, Cees; Heck, Albert J. R.] Univ Utrecht, Bijvoet Ctr Biomol Res, Biomol Mass Spectrometry & Prote Grp, NL-3584 CA Utrecht, Netherlands. [Uetrecht, Charlotte; Versluis, Cees; Heck, Albert J. R.] Univ Utrecht, Utrecht Inst Pharmaceut Sci, NL-3584 CA Utrecht, Netherlands. [Watts, Norman R.; Wingfield, Paul T.] NIAMSD, Protein Express Lab, NIH, Bethesda, MD 20892 USA. [Steven, Alasdair C.] NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. [Wuite, Gijs J. L.] Vrije Univ Amsterdam, NL-1081 HV Amsterdam, Netherlands. RP Heck, AJR (reprint author), Univ Utrecht, Bijvoet Ctr Biomol Res, Biomol Mass Spectrometry & Prote Grp, Sorbonnelaan 16, NL-3584 CA Utrecht, Netherlands. EM a.j.r.heck@uu.nl RI Uetrecht, Charlotte/D-1883-2010; Heck, Albert/D-7098-2011; Roos, Wouter/L-8346-2014 OI Uetrecht, Charlotte/0000-0002-1991-7922; Heck, Albert/0000-0002-2405-4404; Roos, Wouter/0000-0002-5104-0139 FU Intramural NIH HHS [Z01 AR041117-12] NR 41 TC 107 Z9 107 U1 1 U2 43 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 8 PY 2008 VL 105 IS 27 BP 9216 EP 9220 DI 10.1073/pnas.0800406105 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 326GA UT WOS:000257645400017 PM 18587050 ER PT J AU Cocchiaro, JL Kumar, Y Fischer, ER Hackstadt, T Valdivia, RH AF Cocchiaro, Jordan L. Kumar, Yadunanda Fischer, Elizabeth R. Hackstadt, Ted Valdivia, Raphael H. TI Cytoplasmic lipid droplets are translocated into the lumen of the Chlamydia trachomatis parasitophorous vacuole SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ADRP; inclusion; Lda3; organelle translocation ID OBLIGATE INTRACELLULAR PATHOGEN; DIFFERENTIATION-RELATED PROTEIN; INCLUSION MEMBRANE; HOST-CELL; BODIES; METABOLISM; PATHWAY; TRAFFICKING; ASSOCIATION AB The acquisition of host-derived lipids is essential for the pathogenesis of the obligate intracellular bacteria Chlamydia trachomatis. Current models of chlamydial lipid acquisition center on the fusion of Golgi-derived exocytic vesicles and endosomal multivesicular bodies with the bacteria-containing parasitophorous vacuole ("inclusion"). In this study, we describe a mechanism of lipid acquisition and organelle subversion by C. trachomatis. We show by live cell fluorescence microscopy and electron microscopy that lipid droplets (LDs), neutral lipid storage organelles, are translocated from the host cytoplasm into the inclusion lumen. LDs dock at the surface of the inclusion, penetrate the inclusion membrane and intimately associate with reticulate Bodies, the replicative form of Chlamydia. The inclusion membrane protein IncA, but not other inclusion membrane proteins, cofractionated with LDs and accumulated in the inclusion lumen. Therefore, we postulate that the translocation of LDs may occur at IncA-enriched subdomains of the inclusion membrane. Finally, the chlamydial protein Lda3 may participate in the cooption of these organelles by linking cytoplasmic LDs to inclusion membranes and promoting the removal of the LD protective coat protein, adipocyte differentiation related protein (ADRP). The wholesale transport of LDs into the lumen of a parasitophorous vacuole represents a unique mechanism of organelle sequestration and subversion by a bacterial pathogen. C1 [Cocchiaro, Jordan L.; Kumar, Yadunanda; Valdivia, Raphael H.] Duke Univ, Dept Mol Genet & Microbiol, Ctr Microbial Pathogenesis, Med Ctr, Durham, NC 27710 USA. [Fischer, Elizabeth R.] Natl Inst Hlth, Microscopy Unit, RTB Res Technol Sect, Hamilton, MT 59840 USA. [Hackstadt, Ted] Natl Inst Hlth, Rocky Mt Labs, Host Parasite Interact Sect, Hamilton, MT 59840 USA. RP Valdivia, RH (reprint author), Duke Univ, Dept Mol Genet & Microbiol, Ctr Microbial Pathogenesis, Med Ctr, Durham, NC 27710 USA. EM valdi001@mc.duke.edu OI budigi, yadunanda/0000-0003-3784-2431 FU NIAID NIH HHS [AI068032, R01 AI068032, R21 AI061538] NR 37 TC 144 Z9 146 U1 1 U2 14 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 8 PY 2008 VL 105 IS 27 BP 9379 EP 9384 DI 10.1073/pnas.0712241105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 326GA UT WOS:000257645400045 PM 18591669 ER PT J AU Stetler-Stevenson, WG AF Stetler-Stevenson, William G. TI Tissue Inhibitors of Metalloproteinases in Cell Signaling: Metalloproteinase-Independent Biological Activities SO SCIENCE SIGNALING LA English DT Review AB Over the past 20 years, the tissue inhibitors of metalloproteinases (TIMPs) have been implicated in direct regulation of cell growth and apoptosis. However, the mechanisms of these effects have been controversial. Recent work by several laboratories has identified specific signaling pathways and cell surface binding partners for members of the TIMP family. TIMP-2 binding to the integrin alpha(3)beta(1) is the first description of a cell surface receptor for a TIMP family member. TIMP-2 has been shown to induce gene expression, to promote G(1) cell cycle arrest, and to inhibit cell migration. TIMP-1 binding to CD63 inhibits cell growth and apoptosis. These new findings suggest that TIMPs are multifunctional and can act either directly through cell surface receptors or indirectly through modulation of protease activity to direct cell fate. The emerging concept is that TIMPs function in a contextual fashion so that the mechanism of action depends on the tissue microenvironment. C1 NCI, Extracellular Matrix Pathol Sect, Cell & Canc Biol Branch,Vasc Biol Fac, Ctr Canc Res,NIH,Adv Technol Ctr, Bethesda, MD 20892 USA. RP Stetler-Stevenson, WG (reprint author), NCI, Extracellular Matrix Pathol Sect, Cell & Canc Biol Branch,Vasc Biol Fac, Ctr Canc Res,NIH,Adv Technol Ctr, 8717 Grovemont Circle,Room 115, Bethesda, MD 20892 USA. EM sstevenw@mail.nih.gov RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 FU Intramural NIH HHS [Z01 BC010829-01, Z01 SC009179-19] NR 107 TC 224 Z9 227 U1 1 U2 13 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD JUL 8 PY 2008 VL 1 IS 27 AR re6 DI 10.1126/scisignal.127re6 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA V10WG UT WOS:000207493500002 PM 18612141 ER PT J AU Zhu, BP Wu, DW Zhou, QF Shi, J Shung, KK AF Zhu, B. P. Wu, D. W. Zhou, Q. F. Shi, J. Shung, K. K. TI Lead zirconate titanate thick film with enhanced electrical properties for high frequency transducer applications SO APPLIED PHYSICS LETTERS LA English DT Article ID COMPOSITE; MHZ AB Piezoelectric Pb(Zr(0.52)Ti(0.48))O(3) thick film with the thickness around 10 mu m has been deposited on the (111) Pt/Ti/SiO(2)/Si substrate using a ceramic powder/sol-gel solution modified composite method. X-ray diffraction analysis and scanning electron microscopy revealed that the film was in the well-crystallized perovskite phase and crack-free. At 1 kHz, the dielectric constant and the loss were 1925 and 0.015, respectively. The remnant polarization was 42.0 mu C/cm(2) at room temperature. A high frequency single element acoustic transducer fabricated with this film showed a bandwidth at -6 dB of 50% at 156 MHz. (C) 2008 American Institute of Physics. C1 [Zhu, B. P.; Wu, D. W.; Zhou, Q. F.; Shung, K. K.] Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA. [Zhu, B. P.; Wu, D. W.; Zhou, Q. F.; Shung, K. K.] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA. [Shi, J.] Wuhan Univ, Dept Phys, Wuhan 430072, Peoples R China. [Shi, J.] Wuhan Univ, Key Lab Acoust & Photon Mat & Devices, Minist Educ, Wuhan 430072, Peoples R China. RP Zhou, QF (reprint author), Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA. EM qifazhou@usc.edu RI wu, dawei/D-3158-2014 NR 15 TC 21 Z9 21 U1 0 U2 4 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0003-6951 J9 APPL PHYS LETT JI Appl. Phys. Lett. PD JUL 7 PY 2008 VL 93 IS 1 AR 012905 DI 10.1063/1.2956408 PG 3 WC Physics, Applied SC Physics GA 333WP UT WOS:000258184600042 ER PT J AU Brown, PL Kiyatkin, EA AF Brown, P. Leon Kiyatkin, Eugene A. TI Sensory effects of intravenous cocaine on dopamine and non-dopamine ventral tegmental area neurons SO BRAIN RESEARCH LA English DT Article DE somato-sensory stimulus; glutamate; visceral sensory nerve; tail-press; dopamine release and uptake; drug-taking behavior; reinforcement ID CENTRAL-NERVOUS-SYSTEM; FREELY MOVING RATS; SUBSTANTIA-NIGRA; SELECTIVE ACTIVATION; MESOLIMBIC DOPAMINE; PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS; UNRESTRAINED RATS; UPTAKE INHIBITION; IMPULSE ACTIVITY AB Intravenous (iv) cocaine mimics salient somato-sensory stimuli in their ability to induce rapid physiological effects, which appear to involve its action on peripherally located neural elements and fast neural transmission via somato-sensory pathways. To further clarify this mechanism, single-unit recording with fine glass electrodes was used in awake rats to examine responses of ventral tegmental area (VTA) neurons, both presumed dopamine (DA) and nonDA, to iv cocaine and tail-press, a typical somato-sensory stimulus. To exclude the contribution of DA mechanisms to the observed neuronal responses to sensory stimuli and cocaine, recordings were conducted during full DA receptor blockade (SCH23390+eticloptide). Iv cocaine (0.25 mg/kg delivered over 10 s) induced significant excitations of - 63% of long-spike (presumed DA) and - 70% of short-spike (presumed non-DA) VTA neurons. In both subgroups, neuronal excitations occurred with short latencies (4-8 s), peaked at 10-20 s (30-40% increase over baseline) and disappeared at 30-40 s after the injection onset. Most long-(67%) and shortspike (89%) VTA neurons also showed phasic responses to tail-press (5-s). All responsive longspike cells were excited by tail-press; excitations were very rapid (peak at I s) and strong (100% rate increase over baseline) but brief (2-3 s). In contrast, both excitations (60%) and inhibitions (29%) were seen in short-spike cells. These responses were also rapid and transient, but excitations of short-spike units were more prolonged and sustained (10-15 s) than in longspike cells. These data suggest that in awake animals iv cocaine, like somato-sensory stimuli, rapidly and transiently excites VTA neurons of different subtypes. Therefore, along with direct action on specific brain substrates, central effects of cocaine may occur, via an indirect mechanism, involving peripheral neural elements, visceral sensory nerves and rapid neural transmission. Via this mechanism, cocaine, like somato-sensory stimuli, can rapidly activate DA neurons and induce phasic DA release, creating the conditions for DA accumulation by a later occurring and prolonged direct inhibiting action on DA uptake. By providing a rapid neural signal and triggering transient neural activation, such a peripherally driven action might play a crucial role in the sensory effects of cocaine, thus contributing to learning and development of drug-taking behavior. Published by Elsevier B.V. C1 [Brown, P. Leon; Kiyatkin, Eugene A.] Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, Natl Inst Hlth,DHHS, Baltimore, MD 21224 USA. RP Kiyatkin, EA (reprint author), Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, Natl Inst Hlth,DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ekiyatki@intra.nida.nih.gov FU Intramural NIH HHS [Z99 DA999999] NR 86 TC 12 Z9 12 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD JUL 7 PY 2008 VL 1218 BP 230 EP 249 DI 10.1016/j.brainres.2008.04.027 PG 20 WC Neurosciences SC Neurosciences & Neurology GA 331MM UT WOS:000258016300023 PM 18514638 ER PT J AU Sportes, C Hakim, FT Memon, SA Zhang, H Chua, KS Brown, MR Fleisher, TA Krumlauf, MC Babb, RR Chow, CK Fry, TJ Engels, J Buffet, R Morre, M Amato, RJ Venzon, DJ Korngold, R Pecora, A Gress, RE Mackall, CL AF Sportes, Claude Hakim, Frances T. Memon, Sarfraz A. Zhang, Hua Chua, Kevin S. Brown, Margaret R. Fleisher, Thomas A. Krumlauf, Michael C. Babb, Rebecca R. Chow, Catherine K. Fry, Terry J. Engels, Julie Buffet, Renaud Morre, Michel Amato, Robert J. Venzon, David J. Korngold, Robert Pecora, Andrew Gress, Ronald E. Mackall, Crystal L. TI Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID RECENT THYMIC EMIGRANTS; SEVERE COMBINED IMMUNODEFICIENCY; BONE-MARROW-TRANSPLANTATION; HIV-INFECTED PATIENTS; CANCER-PATIENTS; DEFICIENT MICE; IL-7 INCREASES; INTERLEUKIN-7; CD8(+); HOMEOSTASIS AB Interleukin-7 (IL-7) is a homeostatic cytokine for resting T cells with increasing serum and tissue levels during T cell depletion. In preclinical studies, IL-7 therapy exerts marked stimulating effects on T cell immune reconstitution in mice and primates. First-in-human clinical studies of recombinant human IL-7 (rhIL-7) provided the opportunity to investigate the effects of IL-7 therapy on lymphocytes in vivo. rhIL-7 induced in vivo T cell cycling, bcl-2 up-regulation, and a sustained increase in peripheral blood CD4(+) and CD8(+) T cells. This T cell expansion caused a significant broadening of circulating T cell receptor (TCR) repertoire diversity independent of the subjects' age as naive T cells, including recent thymic emigrants (RTEs), expanded preferentially, whereas the proportions of regulatory T (T reg) cells and senescent CD8(+) effectors diminished. The resulting composition of the circulating T cell pool more closely resembled that seen earlier in life. This profile, distinctive among cytokines under clinical development, suggests that rhIL-7 therapy could enhance and broaden immune responses, particularly in individuals with limited naive T cells and diminished TCR repertoire diversity, as occurs after physiological (age), pathological (human immunodeficiency virus), or iatrogenic (chemotherapy) lymphocyte depletion. C1 [Sportes, Claude; Hakim, Frances T.; Memon, Sarfraz A.; Krumlauf, Michael C.; Babb, Rebecca R.; Gress, Ronald E.] NIH, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. [Zhang, Hua; Chua, Kevin S.; Fry, Terry J.; Mackall, Crystal L.] NCI, NIH, Ctr Canc Res, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Chow, Catherine K.] NIH, Dept Radiol, Bethesda, MD 20892 USA. [Fleisher, Thomas A.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Engels, Julie; Buffet, Renaud; Morre, Michel] Cytheris Inc, Rockville, MD 20850 USA. [Korngold, Robert] Methodist Hosp, Texas Med Ctr, Houston, TX 77021 USA. [Venzon, David J.] Natl Canc Inst, Biostat & Data Management Sect, Hackensack, NJ 07601 USA. [Korngold, Robert; Pecora, Andrew] Hackensack Univ, Med Ctr, Ctr Canc, Hackensack, NJ 07601 USA. RP Sportes, C (reprint author), NIH, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. EM csportes@mail.nih.gov RI Memon, Sarfraz/E-1198-2013 FU Intramural Research Program of the National Institutes of Health; National Cancer Institute (NCI); Center for Cancer Research FX The authors would like to thank the subjects who enrolled on this investigational trial and provided consent for research studies and the clinical staff of the National Institutes of Health Clinical Center and of the Experimental Transplantation and Immunology Branch for their excellent care of these subjects. We would also like to thank Drs. Al Singer and Scott Durum for helpful comments and careful reviews of the manuscript.; This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute (NCI), and Center for Cancer Research and was made possible through a formal collaboration (Cooperative Research and Development Agreement [CRADA] # 01649) between the NCI and Cytheris Inc., the investigational new drug holder and manufacturer of rhIL-7, currently developing recombinant human IL-7 for therapeutic use. As per the CRADA between NCI and Cytheris Inc., the NCI investigators designed and conducted all the research experiments and analyses presented in the article independently from Cytheris Inc.; Three co-authors have financial interest in Cytheris capital: M. Morre is the founder and Chief Executive Officer and J. Engels and R. Buffet are employees of Cytheris. All other co-authors have explicitly denied any conflict of interest. NR 52 TC 262 Z9 268 U1 0 U2 10 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 7 PY 2008 VL 205 IS 7 BP 1701 EP 1714 DI 10.1084/jem.20071681 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 338RS UT WOS:000258527000021 PM 18573906 ER PT J AU Mateu, G Donis, RO Wakita, T Bukh, J Grakoui, A AF Mateu, Guaniri Donis, Ruben O. Wakita, Takaji Bukh, Jens Grakoui, Arash TI Intragenotypic JFH1 based recombinant hepatitis C virus produces high levels of infectious particles but causes increased cell death SO VIROLOGY LA English DT Article DE hepatitis C virus; intragenotypic recombinant; JFH; cell death ID CORE PROTEIN; RNA REPLICATION; EFFICIENT REPLICATION; FULMINANT-HEPATITIS; MOLECULAR CLONE; UNITED-STATES; HUH-7 CELLS; GENOTYPE 2A; IN-VITRO; CULTURE AB The full-length hepatitis C virus (HCV)JFH1 genome (genotype 2a) produces moderate titers of infectious particles Received 6 February 2008 in cell culture but the optimal determinants required for virion production are unclear. It has been shown that intragenotypic recombinants encoding core to NS2 from J6CF in the context of JFH1 are more robust in the release of viral particles. To understand the contributions of structural and nonstructural genes to HCV replication potential and infectivity, we have characterized intragenotypic recombinant genotype 2a viruses with different portions of the J6 isolate engineered into the JFH1 infectious clone. All genomes produced high levels of intracellular HCV RNA and NS3 protein in Huh-7.5 transfected cells. However, JFH1 genomes containing J6 sequences from C to E2 (CE2) or C to p7 (Cp7) secreted up to 100-fold more infectious HCV particles than the parental JFH1 clone. Subsequent infection of naive Huh-7.5 cells with each of the J6/JFH1 recombinants at a multiplicity of infection of 0.0003 resulted in high viral titers only for CE2 and Cp7 viruses. Comparison of virion production by the Cp7 J6/JFH1 recombinant to previously described J6/JFH1 recombinants showed flexibility of the chimeric junction. Moreover, NTRNS2 a chimeric virus equivalent to the previously reported FL-j6/JFH chimera, showed a 10-fold enhancement of virus titers compared to CNS2. NTRNS2 differs from CNS2 by three nucleotide differences residing in the 5' NTR and core coding sequence and all three nucleotide changes were necessary for increased virion production. Importantly, cells producing Cp7 virus showed increased apoptosis compared with JFH1, an effect correlating with virion production. These studies begin to unravel requirements for robust virus replication and the relationship between increased virion production and host cell viability. (C) 2008 Elsevier Inc. All rights reserved. C1 [Mateu, Guaniri; Grakoui, Arash] Emory Univ, Sch Med, Dept Med, Div Infect Dis, Atlanta, GA 30329 USA. [Donis, Ruben O.] Ctr Dis Control & Prevent, Mol Virol & Vaccines Branch, Atlanta, GA 30333 USA. [Wakita, Takaji] Natl Inst Infect Dis, Dept Virol 2, Shinjuku Ku, Tokyo 1628640, Japan. [Bukh, Jens] Univ Copenhagen Hosp, Dept Infect Dis, DK-2650 Hvidovre, Denmark. [Bukh, Jens] Univ Copenhagen Hosp, Clin Res Ctr, DK-2650 Hvidovre, Denmark. [Bukh, Jens] Univ Copenhagen, Fac Hlth Sci, Dept Int Hlth Immunol & Microbiol, DK-2200 Copenhagen, Denmark. [Bukh, Jens] NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Grakoui, A (reprint author), Emory Univ, Sch Med, Dept Med, Div Infect Dis, 954 Gatewood Rd, Atlanta, GA 30329 USA. EM arash.grakoui@emory.edu FU NCRR NIH HHS [P51 RR000165, RR-00165, P51 RR000165-48]; NIAID NIH HHS [P30 AI050409, AI052448, AI070101, P30 AI050409-07, R01 AI070101, R01 AI070101-01, R21 AI052448, R21 AI052448-01A1, R56 AI070101]; NIDDK NIH HHS [R01 DK083356] NR 50 TC 44 Z9 45 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JUL 5 PY 2008 VL 376 IS 2 BP 397 EP 407 DI 10.1016/j.virol.2008.03.027 PG 11 WC Virology SC Virology GA 313CG UT WOS:000256718100016 PM 18455749 ER PT J AU Adamik, B Islam, A Rouhani, FN Hawari, FI Zhang, J Levine, SJ AF Adamik, Barbara Islam, Aminul Rouhani, Farshid N. Hawari, Feras I. Zhang, Jing Levine, Stewart J. TI An association between RBMX, a heterogeneous nuclear ribonucleoprotein, and ARTS-1 regulates extracellular TNFR1 release SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE cytokine receptors; inflammation; endothelial cells; cytokines; soluble TNF receptors, TNFR1; TNFR1 exosome-like vesicles; RBMX; heterogeneous nuclear ribonucleprotein; ARTS-1 ID EXOSOME-LIKE VESICLES; HNRNP-G; TRA2-BETA; PROTEIN AB The type I, 55-kDa tumor necrosis factor receptor (TNFR1) is released to the extracellular space by two mechanisms, the constitutive release of TNFR1 exosome-like vesicles and the inducible proteolytic cleavage of TNFR1 ectodomains. Both pathways appear to be regulated by an interaction between TNFR1 and ARTS-1 (aminopeptidase regulator of TNFR1 shedding). Here, we sought to identify ARTS-1-interacting proteins that modulate TNFR1 release. Co-immunoprecipitation identified an association between ARTS-1 and RBMX (RNA-binding motif gene, X chromosome), a 43-kDa heterogeneous nuclear ribonucleoprotein. RNA interference attenuated RBMX expression, which reduced both the constitutive release of TNFR1 exosome-like vesicles and the IL-1 beta-mediated inducible proteolytic cleavage of soluble TNFR1 ectodomains. Reciprocally, over-expression of RBMX increased TNFR1 exosome-like vesicle release and the IL-1 beta-mediated inducible shedding of TNFR1 ectodomains. This identifies RBMX as an ARTS-1-associated protein that regulates both the constitutive release of TNFR1 exosome-like vesicles and the inducible proteolytic cleavage of TNFR1 ectodomains. Published by Elsevier Inc. C1 [Adamik, Barbara; Islam, Aminul; Rouhani, Farshid N.; Hawari, Feras I.; Zhang, Jing; Levine, Stewart J.] NIH, Pulm Crit Care Med Branch, Natl Heart Lung & Blood Inst, Bethesda, MD 20892 USA. RP Levine, SJ (reprint author), NIH, Pulm Crit Care Med Branch, Natl Heart Lung & Blood Inst, Bldg 10,Room 6D03,MSC 1590, Bethesda, MD 20892 USA. EM levines@nhlbi.nih.gov FU Intramural NIH HHS [Z01 HL002544-09] NR 10 TC 16 Z9 18 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 4 PY 2008 VL 371 IS 3 BP 505 EP 509 DI 10.1016/j.bbrc.2008.04.103 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 307KZ UT WOS:000256319100032 PM 18445477 ER PT J AU Miersch, S Espey, MG Chaube, R Akarca, A Tweten, R Ananvoranich, S Mutus, B AF Miersch, Shane Espey, Michael Graham Chaube, Ruchi Akarca, Arzu Tweten, Rodney Ananvoranich, Sirinart Mutus, Bulent TI Plasma membrane cholesterol content affects nitric oxide diffusion dynamics and signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VASODILATOR-STIMULATED PHOSPHOPROTEIN; SOLUBLE GUANYLYL CYCLASE; LOW-DENSITY-LIPOPROTEIN; LIPID RAFTS; ENA/VASP PROTEINS; PROSTATE-CANCER; CELL-MEMBRANES; OXYGEN; DISEASE; INHIBITION AB Nitric oxide (NO) signaling is inextricably linked to both its physical and chemical properties. Due to its preferentially hydrophobic solubility, NO molecules tend to partition from the aqueous milieu into biological membranes. We hypothesized that plasma membrane ordering provided by cholesterol further couples the physics of NO diffusion with cellular signaling. Fluorescence lifetime quenching studies with pyrene liposome preparations showed that the presence of cholesterol decreased apparent diffusion coefficients of NO similar to 20-40%, depending on the phospholipid composition. Electrochemical measurements indicated that the diffusion rate of NO across artificial bilayer membranes were inversely related to cholesterol content. Sterol transport-defective Niemann-Pick type C1 (NPC1) fibroblasts exhibited increased plasma membrane cholesterol content but decreased activation of both intracellular soluble guanylyl cyclase and vasodilator-stimulated phosphoprotein (VASP) phosphorylation at Ser(239) induced by exogenous NO exposure relative to their normal human fibroblast (NHF) counterparts. Augmentation of plasma membrane cholesterol in NHF diminished production of both cGMP and VASP phosphorylation elicited by NO to NPC1-comparable levels. Conversely, decreasing membrane cholesterol in NPC1 resulted in the augmentation in both cGMP and VASP phosphorylation to a level similar to those observed in NHF. Increasing plasma membrane cholesterol contents in NHF, platelets, erythrocytes and tumor cells also resulted in an increased level of extracellular diaminofluorescein nitrosation following NO exposure. These findings suggest that the impact of cholesterol on membrane fluidity and microdomain structure contributes to the spatial heterogeneity of NO diffusion and signaling. C1 [Miersch, Shane; Chaube, Ruchi; Akarca, Arzu; Ananvoranich, Sirinart; Mutus, Bulent] Univ Windsor, Dept Chem & Biochem, Windsor, ON N9B 3P4, Canada. [Tweten, Rodney] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73104 USA. [Espey, Michael Graham] NIDDK, Mol & Clin Nutr Sect, NIH, Bethesda, MD 20892 USA. RP Mutus, B (reprint author), 401 Sunset Ave, Windsor, ON N9B 3P4, Canada. EM mutusb@uwindsor.ca FU NIAID NIH HHS [R01 AI037657] NR 61 TC 28 Z9 28 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 4 PY 2008 VL 283 IS 27 BP 18513 EP 18521 DI 10.1074/jbc.M800440200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 319LR UT WOS:000257165600006 PM 18445594 ER PT J AU Mans, BJ Ribeiro, JMC Andersen, JF AF Mans, Ben J. Ribeiro, Jose M. C. Andersen, John F. TI Structure, function, and evolution of biogenic amine-binding proteins in soft ticks SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ORNITHODOROS-MOUBATA; PLATELET-AGGREGATION; HISTAMINE-BINDING; SALIVARY PROTEINS; INHIBITOR; LIPOCALIN; FAMILY; CLONING; IDENTIFICATION; EXPRESSION AB Two highly abundant lipocalins, monomine and monotonin, have been isolated from the salivary gland of the soft tick Argas monolakensis and shown to bind histamine and 5-hydroxytryptamine (5-HT), respectively. The crystal structures of monomine and a paralog of monotonin were determined in the presence of ligands to compare the determinants of ligand binding. Both the structures and binding measurements indicate that the proteins have a single binding site rather than the two sites previously described for the female-specific histaminebinding protein (FS-HBP), the histamine-binding lipocalin of the tick Rhipicephalus appendiculatus. The binding sites of monomine and monotonin are similar to the lower, low affinity site of FS-HBP. The interaction of the protein with the aliphatic amine group of the ligand is very similar for the all of the proteins, whereas specificity is determined by interactions with the aromatic portion of the ligand. Interestingly, protein interaction with the imidazole ring of histamine differs significantly between the low affinity binding site of FS-HBP and monomine, suggesting that histamine binding has evolved independently in the two lineages. From the conserved features of these proteins, a tick lipocalin biogenic amine-binding motif could be derived that was used to predict biogenic amine-binding function in other tick lipocalins. Heterologous expression of genes from salivary gland libraries led to the discovery of biogenic amine-binding proteins in soft (Ornithodoros) and hard (Ixodes) tick genera. The data generated were used to reconstruct the most probable evolutionary pathway for the evolution of biogenic amine-binding in tick lipocalins. C1 [Mans, Ben J.; Ribeiro, Jose M. C.; Andersen, John F.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Andersen, JF (reprint author), 12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM jandersen@mail.nih.gov OI Mans, Ben/0000-0002-0177-0029; Ribeiro, Jose/0000-0002-9107-0818 FU Intramural NIH HHS NR 43 TC 43 Z9 43 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 4 PY 2008 VL 283 IS 27 BP 18721 EP 18733 DI 10.1074/jbc.M800188200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 319LR UT WOS:000257165600029 PM 18445596 ER PT J AU Shibata, Y Voss, C Rist, JM Hu, J Rapoport, TA Prinz, WA Voeltz, GK AF Shibata, Yoko Voss, Christiane Rist, Julia M. Hu, Junjie Rapoport, Tom A. Prinz, William A. Voeltz, Gia K. TI The reticulon and DP1/Yop1p proteins form immobile oligomers in the tubular endoplasmic reticulum SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LIVING CELLS; FUNCTIONAL DOMAINS; MEMBRANE CURVATURE; DYNAMICS; ORGANIZATION; MICROTUBULES; INHERITANCE; SPIRALS; SHEETS; NOGO AB We recently identified a class of membrane proteins, the reticulons and DP1/Yop1p, which shape the tubular endoplasmic reticulum ( ER) in yeast and mammalian cells. These proteins are highly enriched in the tubular portions of the ER and virtually excluded from other regions. To understand how they promote tubule formation, we characterized their behavior in cellular membranes and addressed how their localization in the ER is determined. Using fluorescence recovery after photobleaching, we found that yeast Rtn1p and Yop1p are less mobile in the membrane than normal ER proteins. Sucrose gradient centrifugation and cross-linking analyses show that they form oligomers. Mutants of yeast Rtn1p, which no longer localize exclusively to the tubular ER or are even totally inactive in inducing ER tubules, are more mobile and oligomerize less extensively. The mammalian reticulons and DP1 are also relatively immobile and can form oligomers. The conserved reticulon homology domain that includes the two membrane-embedded segments is sufficient for the localization of the reticulons to the tubular ER, as well as for their diffusional immobility and oligomerization. Finally, ATP depletion in both yeast and mammalian cells further decreases the mobilities of the reticulons and DP1. We propose that oligomerization of the reticulons and DP1/Yop1p is important for both their localization to the tubular domains of the ER and for their ability to form tubules. C1 [Voss, Christiane; Prinz, William A.] NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. [Shibata, Yoko; Rist, Julia M.; Hu, Junjie; Rapoport, Tom A.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Shibata, Yoko; Rist, Julia M.; Hu, Junjie; Rapoport, Tom A.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Voeltz, Gia K.] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA. RP Prinz, WA (reprint author), NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. EM wprinz@helix.nih.gov; gia.voeltz@colorado.edu RI Hu, Junjie/F-9713-2013 FU Howard Hughes Medical Institute; Intramural NIH HHS NR 33 TC 149 Z9 153 U1 0 U2 20 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 4 PY 2008 VL 283 IS 27 BP 18892 EP 18904 DI 10.1074/jbc.M800986200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 319LR UT WOS:000257165600046 PM 18442980 ER PT J AU Suh, JY Cai, ML Clore, GM AF Suh, Jeong-Yong Cai, Mengli Clore, G. Marius TI Impact of phosphorylation on structure and thermodynamics of the interaction between the N-terminal domain of enzyme I and the histidine phosphocarrier protein of the bacterial phosphotransferase system SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RESIDUAL DIPOLAR COUPLINGS; GLOBAL REPRESSOR MLC; ESCHERICHIA-COLI; SUGAR-TRANSPORT; CARBOHYDRATE TRANSPORTERS; SALMONELLA-TYPHIMURIUM; MANNITOL TRANSPORTER; RESOLUTION STRUCTURE; GLUCOSE-TRANSPORTER; TRANSFER COMPLEX AB The structural and thermodynamic impact of phosphorylation on the interaction of the N-terminal domain of enzyme I (EIN) and the histidine phosphocarrier protein (HPr), the two common components of all branches of the bacterial phosphotransferase system, have been examined using NMR spectroscopy and isothermal titration calorimetry. His-189 is located at the interface of the alpha and alpha beta domains of EIN, resulting in rather widespread chemical shift perturbation upon phosphorylation, in contrast to the highly localized perturbations seen for HPr, where His-15 is fully exposed to solvent. Residual dipolar coupling measurements, however, demonstrate unambiguously that no significant changes in backbone conformation of either protein occur upon phosphorylation: for EIN, the relative orientation of the alpha and alpha beta domains remains unchanged; for HPr, the backbone phi/psi torsion angles of the active site residues are unperturbed within experimental error. His 3 Glu/Asp mutations of the active site histidines designed to mimic the phosphorylated states reveal binding equilibria that favor phosphoryl transfer from EIN to HPr. Although binding of phospho-EIN to phospho-HPr is reduced by a factor of similar to 21 relative to the unphosphorylated complex, residual dipolar coupling measurements reveal that the structures of the unphosphorylated and biphosphorylated complexes are the same. Hence, the phosphorylation states of EIN and HPr shift the binding equilibria predominantly by modulating intermolecular electrostatic interactions without altering either the backbone scaffold or binding interface. This facilitates highly efficient phosphoryl transfer between EIN and HPr, which is estimated to occur at a rate of similar to 850 s(-1) from exchange spectroscopy. C1 [Suh, Jeong-Yong; Cai, Mengli; Clore, G. Marius] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. EM mariusc@mail.nih.gov RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 FU Intramural NIH HHS NR 44 TC 22 Z9 22 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 4 PY 2008 VL 283 IS 27 BP 18980 EP 18989 DI 10.1074/jbc.M802211200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 319LR UT WOS:000257165600054 PM 18445588 ER PT J AU Martin, RG Bartlett, ES Rosner, JL Wall, ME AF Martin, Robert G. Bartlett, Emily S. Rosner, Judah L. Wall, Michael E. TI Activation of the Escherichia coli marA/soxS/rob regulon in response to transcriptional activator concentration SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE gene regulation; AraC protein family; stress response ID ANTIBIOTIC-RESISTANCE OPERON; SOXS BINDING-SITES; LON PROTEASE; PROMOTERS; MARA; MARRAB; DEGRADATION; ORIENTATION; MECHANISM; BACTERIA AB The paralogous transcriptional activators MarA, SoxS, and Rob activate a common set of promoters, the marA/soxS/rob regulon of Escherichia coli, by binding a cognate site (marbox) upstream of each promoter. The extent of activation varies from one promoter to another and is only poorly correlated with the in vitro affinity of the activator for the specific marbox. Here, we examine the dependence of promoter activation on the level of activator in vivo by manipulating the steady-state concentrations of MarA and SoxS in Lon protease mutants and by measuring promoter activation using lacZ transcriptional fusions. We found that: (i) the MarA concentrations needed for half-maximal stimulation varied by at least 19-fold among the 10 promoters tested; (ii) most marboxes were not saturated when there were 24,000 molecules of MarA per cell; (iii) the correlation between the MarA concentration needed for half-maximal promoter activity in vivo and marbox binding affinity in vitro was poor; and (iv) the two activators differed in their promoter activation profiles. The marRAB and sodA promoters could both be saturated by MarA and SoxS in vivo. However, saturation by MarA resulted in greater marRAB and lesser sodA transcription than did saturation by SoxS, implying that the two activators interact with RNA polymerase in different ways at the different promoters. Thus, the concentration and nature of activator determine which regulon promoters are activated, as well as the extent of their activation. Published by Elsevier Ltd. C1 [Martin, Robert G.; Bartlett, Emily S.; Rosner, Judah L.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Wall, Michael E.] Los Alamos Natl Lab, Comp Computat & Stat Sci Div, Biosci Div, Los Alamos, NM 87545 USA. [Wall, Michael E.] Los Alamos Natl Lab, Ctr Nonlinear Studies, Los Alamos, NM 87545 USA. RP Martin, RG (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM rgmartin@helix.nih.gov OI Alexandrov, Ludmil/0000-0003-3596-4515 FU Intramural NIH HHS [Z01 DK036116-16] NR 28 TC 36 Z9 36 U1 0 U2 4 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUL 4 PY 2008 VL 380 IS 2 BP 278 EP 284 DI 10.1016/j.jmb.2008.05.015 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 326AJ UT WOS:000257630000002 PM 18514222 ER PT J AU Kubler-Kielb, J Vinogradov, E Ben-Menachem, G Pozsgay, V Robbins, JB Schneerson, R AF Kubler-Kielb, Joanna Vinogradov, Evgeny Ben-Menachem, Gil Pozsgay, Vince Robbins, John B. Schneerson, Rachel TI Saccharide/protein conjugate vaccines for Bordetella species: Preparation of saccharide, development of new conjugation procedures, and physico-chemical and immunological characterization of the conjugates SO VACCINE LA English DT Article DE Bordetella; LPS; vaccine; conjugate ID SHIGELLA-DYSENTERIAE TYPE-1; O-SPECIFIC POLYSACCHARIDE; BACILLUS-ANTHRACIS; IGG ANTIBODIES; LIPID-A; BRONCHISEPTICA; LIPOPOLYSACCHARIDES; PERTUSSIS; PARAPERTUSSIS; IMMUNOGENICITY AB Bordetellae are Gram-negative bacilli causing respiratory tract infections of mammals and birds. Clinically important are B. pertussis, B. parapertussis and B. bronchiseptica. B. pertussis vaccines have been successful in preventing pertussis in infants and children. Veterinary vaccines against B. bronchiseptica are available, but their efficacy and mode of action are not established. There is no vaccine against B. parapertussis. Based on the concept that immunity to non-capsulated Gram-negative bacteria may be conferred by serum IgG anti-LPS we studied chemical, serological and immunological properties of the O-specific polysaccharides (O-SP) of B. bronchiseptica and B. parapertussis obtained by different degradation procedures. One type of the B. parapertussis and two types of B. bronchiseptica O-SP were recognized based on the structure of their non-reducing end saccharide; no cross-reaction between the two B. bronchiseptica types was observed. Competitive inhibition assays showed the immunodominance of the non-reducing end of these O-SP. Conjugates of B. bronchiseptica and B. parapertussis O-SP were prepared by two methods: using the anhydro-Kdo residue exposed by mild acid hydrolysis of the LPS or the 2,5-anhydromannose residue exposed by deamination of the core glucosamine of the LPS, for binding to an aminooxylated protein. Both coupling methods were carried out at a neutral pH, room temperature, and in a short time. All conjugates, injected as saline solutions at a fraction of an estimated human dose, induced antibodies in mice to the homologous O-SP. These methodologies can be applied to prepare O-SP-based vaccines against other Gram-negative bacteria. Published by Elsevier Ltd. C1 [Kubler-Kielb, Joanna; Ben-Menachem, Gil; Pozsgay, Vince; Robbins, John B.; Schneerson, Rachel] NICHHD, NIH, Bethesda, MD 20892 USA. [Vinogradov, Evgeny] Natl Res Council Canada, Inst Biol Sci, Ottawa, ON K1A 0R6, Canada. RP Kubler-Kielb, J (reprint author), NICHHD, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM kielbj@mail.nih.gov OI Vinogradov, Evgeny/0000-0002-5364-1376 FU Intramural NIH HHS [Z99 HD999999] NR 47 TC 23 Z9 23 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JUL 4 PY 2008 VL 26 IS 29-30 BP 3587 EP 3593 DI 10.1016/j.vaccine.2008.04.079 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 326HK UT WOS:000257649000006 PM 18539367 ER PT J AU Kemp, TJ Garcia-Pineres, A Falk, RT Poncelet, S Dessy, F Giannini, SL Rodriguez, AC Porras, C Herrero, R Hildesheim, A Pinto, LA AF Kemp, Troy J. Garcia-Pineres, Alfonso Falk, Roni T. Poncelet, Sylviane Dessy, Francis Giannini, Sandra L. Rodriguez, Ana Cecilia Porras, Carolina Herrero, Rolando Hildesheim, Allan Pinto, Ligia A. CA Costa Rica Vaccine Trial CVT Grp TI Evaluation of systemic and mucosal anti-HPV16 and anti-HPV18 antibody responses from vaccinated women SO VACCINE LA English DT Article DE human papillomavirus; neutralization assay; cervical secretions ID HUMAN-PAPILLOMAVIRUS TYPE-16; VIRUS-LIKE PARTICLES; RANDOMIZED CONTROLLED-TRIAL; YOUNG-WOMEN; NEUTRALIZING EPITOPES; QUADRIVALENT VACCINE; SUSTAINED EFFICACY; CERVICAL-CANCER; DOUBLE-BLIND; COSTA-RICA AB Ideal methods to monitor HPV neutralizing antibodies induced by vaccination have not been established yet. Here, we evaluated systemic and cervical antibody levels induced by HPV16/18 AS04-adjuvanted vaccine (GlaxoSmithKline Biologicals) using a secreted alkaline phosphatase neutralization assay (SEAP-NA) and enzyme-linked immunosorbent assay (ELISA). Serum and cervical secretions from 50 vaccinated women were used to assess (1) overall assay reproducibility; (2) inter-assay and inter-specimen correlation; (3) correlations between month I and month 12 titers. Strong correlations between SEAP-NA and ELISA were observed (serum anti-HPV16/18, rho = 0.91/0.85; cervix anti-HPV16/18, rho = 0.84/0.89). Systemic and cervical antibody measures also correlated well (rho range: 0.64-0.75); except at mid-cycle (rho range: 0.28-0.65). Correlations between antibody levels at 1 and 12 months following the start of vaccination were poor (rho range: 0.16-0.38). In conclusion, HPV16/18 VLP-based ELISA is a reliable and valid method to monitor anti-HPV16/18 neutralizing potential for the first year following vaccination; however, additional studies will be required to better define the effects of the time on cycle and patterns of antibody response over time following vaccination. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Kemp, Troy J.; Garcia-Pineres, Alfonso; Pinto, Ligia A.] NCI Frederick, SAIC Frederick Inc, HPV Immunol Lab, Frederick, MD 21702 USA. [Falk, Roni T.; Hildesheim, Allan] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Poncelet, Sylviane; Dessy, Francis; Giannini, Sandra L.] GlaxoSmithKline Biol, Res & Dev, B-1330 Rixensart, Belgium. [Rodriguez, Ana Cecilia; Porras, Carolina; Herrero, Rolando] Proyecto Epidemiol Guanacaste, San Jose, Costa Rica. RP Pinto, LA (reprint author), NCI Frederick, SAIC Frederick Inc, HPV Immunol Lab, Bldg 469,Room 120, Frederick, MD 21702 USA. EM lpinto@ncifcrf.gov RI Hildesheim, Allan/B-9760-2015 OI Hildesheim, Allan/0000-0003-0257-2363 FU Intramural NIH HHS [ZIA CP010217-3]; NCI NIH HHS [N01-CO-12400, N01CO12400, N01CP11005] NR 31 TC 55 Z9 56 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JUL 4 PY 2008 VL 26 IS 29-30 BP 3608 EP 3616 DI 10.1016/j.vaccine.2008.04.074 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 326HK UT WOS:000257649000009 PM 18541349 ER PT J AU Temchura, VV Tenbusch, M Nchinda, G Nabi, G Tippler, B Zelenyuk, M Wildner, O Uberla, K Kuate, S AF Temchura, Vladimir V. Tenbusch, Matthias Nchinda, Godwin Nabi, Ghulam Tippler, Bettina Zelenyuk, Maryna Wildner, Oliver Ueberla, Klaus Kuate, Seraphin TI Enhancement of immunostimulatory properties of exosomal vaccines by incorporation of fusion-competent G protein of vesicular stomatitis virus SO VACCINE LA English DT Article DE exosomes; VSV-G; vaccines ID CELL-DERIVED EXOSOMES; CLASS-I MOLECULES; DENDRITIC CELLS; IMMUNODEFICIENCY-VIRUS; LENTIVIRAL VECTORS; TUMOR REJECTION; T-CELLS; ANTIGENS; GLYCOPROTEIN; EXPRESSION AB Exosomes have been proposed as candidates for therapeutic immunization. The present study demonstrates that incorporation of the G protein of vesicular stomatitis virus (VSV-G) into exosome-like vesicles (ELVs) enhances their uptake and induces the maturation of dendritic cells. Targeting of VSV-G and ovalbumin as a model antigen to the same ELVs increased the cross-presentation of ovalbumin via an endosomal acidification mechanism. Immunization of mice with VSV-G and ovalbumin containing ELVs led to an increased IgG2a antibody response, expansion of antigen-specific CD8 T cells, strong in vivo CTL responses, and protection from challenge with ovalbumin expressing tumor cells. Thus, incorporation of VSV-G and targeting of antigens to ELVs are attractive strategies to improve exosomal vaccines. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Temchura, Vladimir V.; Tenbusch, Matthias; Nchinda, Godwin; Nabi, Ghulam; Tippler, Bettina; Zelenyuk, Maryna; Wildner, Oliver; Ueberla, Klaus; Kuate, Seraphin] Ruhr Univ Bochum, Dept Mol & Med Virol, D-44780 Bochum, Germany. RP Kuate, S (reprint author), NIH, VB, CCR, NCI, 41 Medlars Dr MSC 5065,Bldg 41,Room D310, Bethesda, MD 20892 USA. EM kuates@mail.nih.gov RI Uberla, Klaus/C-5676-2008 NR 32 TC 21 Z9 21 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JUL 4 PY 2008 VL 26 IS 29-30 BP 3662 EP 3672 DI 10.1016/j.vaccine.2008.04.069 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 326HK UT WOS:000257649000016 PM 18538453 ER PT J AU Parimi, N Tromp, G Kuivaniemi, H Nien, JK Gomez, R Romero, R Goddard, KAB AF Parimi, Neeta Tromp, Gerard Kuivaniemi, Helena Nien, Jyh Kae Gomez, Ricardo Romero, Roberto Goddard, Katrina A. B. TI Analytical approaches to detect maternal/fetal genotype incompatibilities that increase risk of pre-eclampsia SO BMC MEDICAL GENETICS LA English DT Article ID MAJOR-HISTOCOMPATIBILITY-COMPLEX; NECROSIS-FACTOR-ALPHA; UMBILICAL-CORD; MFG TEST; GENES; PREGNANCY; WOMEN; ASSOCIATION; SUSCEPTIBILITY; SCHIZOPHRENIA AB Background: In utero interactions between incompatible maternal and fetal genotypes are a potential mechanism for the onset or progression of pregnancy related diseases such as pre-eclampsia (PE). However, the optimal analytical approach and study design for evaluating incompatible maternal/offspring genotype combinations is unclear. Methods: Using simulation, we estimated the type I error and power of incompatible maternal/offspring genotype models for two analytical approaches: logistic regression used with case-control mother/offspring pairs and the log-linear regression used with case-parent triads. We evaluated a real dataset consisting of maternal/offspring pairs with and without PE for incompatibility effects using the optimal analysis based on the results of the simulation study. Results: We identified a single coding scheme for the incompatibility effect that was equally or more powerful than all of the alternative analysis models evaluated, regardless of the true underlying model for the incompatibility effect. In addition, the log-linear regression was more powerful than the logistic regression when the heritability was low, and more robust to adjustment for maternal or fetal effects. For the PE data, this analysis revealed three genes, lymphotoxin alpha (LTA), von Willebrand factor (VWF), and alpha 2 chain of type IV collagen (COL4A2) with possible incompatibility effects. Conclusion: The incompatibility model should be evaluated for complications of pregnancy, such as PE, where the genotypes of two individuals may contribute to the presence of disease. C1 [Nien, Jyh Kae; Gomez, Ricardo; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, Bethesda, MD 20892 USA. [Parimi, Neeta; Goddard, Katrina A. B.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. [Tromp, Gerard; Kuivaniemi, Helena] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Tromp, Gerard] Wayne State Univ, Dept Neurol, Detroit, MI USA. [Kuivaniemi, Helena] Wayne State Univ, Dept Surg, Detroit, MI USA. [Gomez, Ricardo] Pontificia Univ Catolica Chile, Ctr Perinatal Diag & Res, Sotero Rio Hosp, Santiago, Chile. [Goddard, Katrina A. B.] Kaiser Permanente NW, Ctr Hlth Res, Portland, OR USA. RP Romero, R (reprint author), NICHD, Perinatol Res Branch, NIH, Bethesda, MD 20892 USA. EM NParimi@sfcc-cpmc.net; Gerard.tromp@sanger.med.wayne.edu; kuivan@sanger.med.wayne.edu; jknien@cedip.cl; rgomez@cedip.cl; prbchiefstaff@med.wayne.edu; Katrina.ab.goddard@kpchr.org RI Tromp, Gerard/B-2677-2017; OI Tromp, Gerard/0000-0002-7761-0806; Kuivaniemi, Helena/0000-0001-5753-8766 FU NCRR NIH HHS [P41 RR003655, RR03655] NR 51 TC 16 Z9 17 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PD JUL 3 PY 2008 VL 9 AR 60 DI 10.1186/1471-2350-9-60 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 327QU UT WOS:000257744400001 PM 18598365 ER PT J AU Lee, H Larson, RG AF Lee, Hwankyu Larson, Ronald G. TI Coarse-grained molecular dynamics studies of the concentration and size dependence of fifth- and seventh-generation PAMAM dendrimers on pore formation in DMPC bilayer SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID SUPPORTED LIPID-BILAYERS; POLY(AMIDOAMINE) DENDRIMERS; POLYCATIONIC POLYMERS; STARBURST DENDRIMERS; INTERNAL STRUCTURE; LATERAL DIFFUSION; DILUTE-SOLUTION; HOLE FORMATION; DRUG-DELIVERY; SIMULATIONS AB We have performed molecular dynamics (MD) simulations of multiple copies of unacetylated G5 and G7 and acetylated G5 dendrimers in dimyristoylphosphatidylcholine bilayers with explicit water using the coarse-grained model developed by Marrink et al. (J. Phys. Chem. B 2007, 111, 7812) with the inclusion of long-range electrostatics. When initially clustered together near the bilayer, neutral acetylated dendrimers aggregate, whereas cationic unacetylated dendrimers do not aggregate, but separate from each other, similar to the observations from atomic force microscopy by Mecke et al. (Chem. Phys. Lipids 2004, 132, 3). The bilayers interacting with unacetylated dendrimers of higher concentration are significantly. deformed and show pore formation on the positively curved portions, while acetylated dendrimers are unable to form pores. Unacetylated G7 dendrimers bring more water molecules into the pores than do unacetylated G5 dendrimers. These results agree qualitatively with experimental results showing that significant cytoplasmic-protein leakage is produced by unacetylated G7 dendrimers at concentrations as low as 10 nM, but only at a much higher concentration of 400 nM for unacetylated G5 dendrimers (Bioconjugate Chem. 2004, 15, 774). This good qualitative agreement indicates that the effect on pore formation of the concentration and size of large nanoparticles can be studied through coarse-grained MD simulations, provided that long-range electrostatic interactions are included. C1 [Lee, Hwankyu] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. [Larson, Ronald G.] Univ Michigan, Dept Chem Engn Biomed Engn Mech Engn, Ann Arbor, MI 48109 USA. [Larson, Ronald G.] Univ Michigan, Macromol Sci & Engn Program, Ann Arbor, MI 48109 USA. RP Lee, H (reprint author), NHLBI, Lab Computat Biol, NIH, Bldg 10, Bethesda, MD 20892 USA. EM leeh3@nhlbi.nih.gov FU Intramural NIH HHS [NIH0013263008]; PHS HHS [NIH0013263008] NR 31 TC 96 Z9 96 U1 3 U2 30 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD JUL 3 PY 2008 VL 112 IS 26 BP 7778 EP 7784 DI 10.1021/jp802606y PG 7 WC Chemistry, Physical SC Chemistry GA 319HT UT WOS:000257155400013 PM 18543869 ER PT J AU Conrad, KL Tseng, KY Uejima, JL Reimers, JM Heng, LJ Shaham, Y Marinelli, M Wolf, ME AF Conrad, Kelly L. Tseng, Kuei Y. Uejima, Jamie L. Reimers, Jeremy M. Heng, Li-Jun Shaham, Yavin Marinelli, Michela Wolf, Marina E. TI Formation of accumbens GluR2-lacking AMPA receptors mediates incubation of cocaine craving SO NATURE LA English DT Article ID CULTURED HIPPOCAMPAL-NEURONS; NUCLEUS-ACCUMBENS; SURFACE EXPRESSION; SYNAPTIC PLASTICITY; BEHAVIORAL SENSITIZATION; DOPAMINE-RECEPTORS; SEEKING BEHAVIOR; NMDA RECEPTORS; RAT; ADDICTION AB Relapse to cocaine use after prolonged abstinence is an important clinical problem. This relapse is often induced by exposure to cues associated with cocaine use. To account for the persistent propensity for relapse, it has been suggested(1) that cue- induced cocaine craving increases over the first several weeks of abstinence and remains high for extended periods. We and others identified an analogous phenomenon in rats that was termed 'incubation of cocaine craving': time- dependent increases in cue- induced cocaine- seeking over the first months after withdrawal from self- administered cocaine(2-4). Cocaine- seeking requires the activation of glutamate projections that excite receptors for alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid ( AMPA) in the nucleus accumbens(5-7). Here we show that the number of synaptic AMPA receptors in the accumbens is increased after prolonged withdrawal from cocaine self-administration by the addition of new AMPA receptors lacking glutamate receptor 2 ( GluR2). Furthermore, we show that these new receptors mediate the incubation of cocaine craving. Our results indicate that GluR2- lacking AMPA receptors could be a new target for drug development for the treatment of cocaine addiction. We propose that after prolonged withdrawal from cocaine, increased numbers of synaptic AMPA receptors combined with the higher conductance of GluR2- lacking AMPA receptors(8,9) causes increased reactivity of accumbens neurons to cocaine- related cues, leading to an intensification of drug craving and relapse. C1 [Conrad, Kelly L.; Reimers, Jeremy M.; Wolf, Marina E.] Rosalind Franklin Univ Med & Sci, Dept Neurosci, N Chicago, IL 60064 USA. [Tseng, Kuei Y.; Heng, Li-Jun; Marinelli, Michela] Rosalind Franklin Univ Med & Sci, Dept Mol & Cellular Pharmacol, N Chicago, IL 60064 USA. [Uejima, Jamie L.; Shaham, Yavin] NIDA, Behav Neurosci Branch, IRP, NIH, Baltimore, MD 21224 USA. RP Wolf, ME (reprint author), Rosalind Franklin Univ Med & Sci, Dept Neurosci, 3333 Green Bay Rd, N Chicago, IL 60064 USA. EM marina.wolf@rosalindfranklin.edu RI shaham, yavin/G-1306-2014 FU Intramural NIH HHS [Z01 DA000434-08]; NIDA NIH HHS [DA00453, DA015835, DA020654, DA09621, K02 DA000453, R01 DA009621, R01 DA015835, R01 DA020654, R37 DA015835] NR 50 TC 411 Z9 415 U1 2 U2 30 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUL 3 PY 2008 VL 454 IS 7200 BP 118 EP U9 DI 10.1038/nature06995 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 321MC UT WOS:000257308300049 PM 18500330 ER PT J AU Palevsky, PM Zhang, JHY O'Connor, TZ Chertow, GM Crowley, ST Choudhury, D Finkel, K Kellum, JA Paganini, E Schein, RMH Smith, MW Swanson, KM Thompson, BT Vijayan, A Watnick, S Star, RA Peduzzi, P AF Palevsky, Paul M. Zhang, Jane Hongyuan O'Connor, Theresa Z. Chertow, Glenn M. Crowley, Susan T. Choudhury, Devasmita Finkel, Kevin Kellum, John A. Paganini, Emil Schein, Roland M. H. Smith, Mark W. Swanson, Kathleen M. Thompson, B. Taylor Vijayan, Anitha Watnick, Suzanne Star, Robert A. Peduzzi, Peter CA VA NIH Acute Renal Failure Trial TI Intensity of renal support in critically ill patients with acute kidney injury SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CONTINUOUS VENOVENOUS HEMOFILTRATION; REPLACEMENT THERAPY; CARE-UNIT; RANDOMIZED-TRIAL; FAILURE; MULTICENTER; EXPERIENCE; MANAGEMENT; MORTALITY; SURVIVAL AB Background: The optimal intensity of renal-replacement therapy in critically ill patients with acute kidney injury is controversial. Methods: We randomly assigned critically ill patients with acute kidney injury and failure of at least one nonrenal organ or sepsis to receive intensive or less intensive renal-replacement therapy. The primary end point was death from any cause by day 60. In both study groups, hemodynamically stable patients underwent intermittent hemodialysis, and hemodynamically unstable patients underwent continuous venovenous hemodiafiltration or sustained low-efficiency dialysis. Patients receiving the intensive treatment strategy underwent intermittent hemodialysis and sustained low-efficiency dialysis six times per week and continuous venovenous hemodiafiltration at 35 ml per kilogram of body weight per hour; for patients receiving the less-intensive treatment strategy, the corresponding treatments were provided thrice weekly and at 20 ml per kilogram per hour. Results: Baseline characteristics of the 1124 patients in the two groups were similar. The rate of death from any cause by day 60 was 53.6% with intensive therapy and 51.5% with less-intensive therapy (odds ratio, 1.09; 95% confidence interval, 0.86 to 1.40; P=0.47). There was no significant difference between the two groups in the duration of renal-replacement therapy or the rate of recovery of kidney function or nonrenal organ failure. Hypotension during intermittent dialysis occurred in more patients randomly assigned to receive intensive therapy, although the frequency of hemodialysis sessions complicated by hypotension was similar in the two groups. Conclusions: Intensive renal support in critically ill patients with acute kidney injury did not decrease mortality, improve recovery of kidney function, or reduce the rate of nonrenal organ failure as compared with less-intensive therapy involving a defined dose of intermittent hemodialysis three times per week and continuous renal-replacement therapy at 20 ml per kilogram per hour. (ClinicalTrials.gov number, NCT00076219.). C1 [Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. [Chertow, Glenn M.] Stanford Univ, Palo Alto, CA 94304 USA. [Zhang, Jane Hongyuan; O'Connor, Theresa Z.; Crowley, Susan T.; Peduzzi, Peter] VA Connecticut Healthcare Syst, CSP Coordinating Ctr, West Haven, CT USA. [Choudhury, Devasmita] VA N Texas Healthcare Syst, Dallas, TX USA. [Kellum, John A.] Univ Pittsburgh, Pittsburgh, PA USA. [Paganini, Emil] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Schein, Roland M. H.] Miami VA Healthcare Syst, Miami, FL USA. [Smith, Mark W.] VA Palo Alto Hlth Care Syst, Hlth Econ Resource Ctr, Menlo Pk, CA USA. [Swanson, Kathleen M.] Clin Res Pharm Coordinating Ctr, CSP, Albuquerque, NM USA. [Thompson, B. Taylor] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Star, Robert A.] NIDDK, Bethesda, MD 20892 USA. RP Palevsky, PM (reprint author), VA Pittsburgh Healthcare Syst, Rm 7E123 111F-U,Univ Dr, Pittsburgh, PA 15240 USA. EM palevsky@pitt.edu RI Smith, Mark/G-1522-2012 OI Smith, Mark/0000-0002-4582-9088 NR 31 TC 624 Z9 673 U1 0 U2 14 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 3 PY 2008 VL 359 IS 1 BP 7 EP 20 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 320PB UT WOS:000257246000003 ER PT J AU Lee, JH Schneider, B Jordan, EK Liu, W Frank, JA AF Lee, Jae-Ho Schneider, Benjamin Jordan, Elaine K. Liu, Wei Frank, Joseph A. TI Synthesis of complexable fluorescent superparamagnetic iron oxide nanoparticles (FL SPIONs) and cell labeling for clinical application SO ADVANCED MATERIALS LA English DT Article ID TRANSFECTION AGENTS; CONTRAST AGENTS; STEM-CELLS; MRI; FERUMOXIDES; DELIVERY; PROBES; DRUG AB we describe a new synthesis route for fluorescent superparamagnetic iron oxide nanoparticles (FL SPIONs) and the self-assembled complex formed using FL SPION and protamine sulfate for cell labeling. This synthesis route involves the conjugation of the FDA-approved dextran-coated ferumoxides with fluorescent dextran. The novel nanostructure of FL SPION is stable in vitro and it complexes with a cationic peptide. C1 [Lee, Jae-Ho; Jordan, Elaine K.; Liu, Wei; Frank, Joseph A.] NIH, Expt Neuroimaging Sect, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. [Schneider, Benjamin] Univ Maryland, Dept Chem Engn, College Pk, MD 20742 USA. [Liu, Wei] Philips Res N Amer, Briarcliff Manor, NY 10510 USA. RP Lee, JH (reprint author), NIH, Expt Neuroimaging Sect, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. EM leejaeho@mail.nih.gov FU Intramural NIH HHS [Z01 CL090004-14] NR 18 TC 32 Z9 33 U1 0 U2 14 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0935-9648 J9 ADV MATER JI Adv. Mater. PD JUL 2 PY 2008 VL 20 IS 13 BP 2512 EP + DI 10.1002/adma.200800223 PG 6 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 328OW UT WOS:000257808700009 PM 19578472 ER PT J AU Alves, G Ogurtsov, AY Kwok, S Wu, WW Wang, GH Shen, RF Yu, YK AF Alves, Gelio Ogurtsov, Aleksey Y. Kwok, Siwei Wu, Wells W. Wang, Guanghui Shen, Rong-Fong Yu, Yi-Kuo TI Detection of co-eluted peptides using database search methods SO BIOLOGY DIRECT LA English DT Article ID TANDEM MASS-SPECTROMETRY; COLLISION-INDUCED DISSOCIATION; PROTEIN IDENTIFICATION; LIQUID-CHROMATOGRAPHY; QUANTITATIVE-ANALYSIS; YEAST PROTEOME; SPECTRA; MS/MS; STATISTICS; PREDICTION AB Background: Current experimental techniques, especially those applying liquid chromatography mass spectrometry, have made high-throughput proteomic studies possible. The increase in throughput however also raises concerns on the accuracy of identification or quantification. Most experimental procedures select in a given MS scan only a few relatively most intense parent ions, each to be fragmented (MS(2)) separately, and most other minor co-eluted peptides that have similar chromatographic retention times are ignored and their information lost. Results: We have computationally investigated the possibility of enhancing the information retrieval during a given LC/MS experiment by selecting the two or three most intense parent ions for simultaneous fragmentation. A set of spectra is created via superimposing a number of MS2 spectra, each can be identified by all search methods tested with high confidence, to mimick the spectra of co-eluted peptides. The generated convoluted spectra were used to evaluate the capability of several database search methods - SEQUEST, Mascot, X! Tandem, OMSSA, and RAld_DbS - in identifying true peptides from superimposed spectra of co-eluted peptides. We show that using these simulated spectra, all the database search methods will gain eventually in the number of true peptides identified by using the compound spectra of co-eluted peptides. Open peer review: Reviewed by Vlad Petyuk (nominated by Arcady Mushegian), King Jordan and Shamil Sunyaev. For the full reviews, please go to the Reviewers' comments section. C1 [Alves, Gelio; Ogurtsov, Aleksey Y.; Yu, Yi-Kuo] NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Kwok, Siwei] Univ Maryland, Dept Math, College Pk, MD 20742 USA. [Wu, Wells W.; Wang, Guanghui; Shen, Rong-Fong] NHLBI, NIH, Prote Core Facil, Bethesda, MD 20892 USA. RP Yu, YK (reprint author), NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM alves@ncbi.nlm.nih.gov; ogurtsov@ncbi.nlm.nih.gov; skwok@umd.edu; wuw2@nhlbi.nih.gov; wangg2@nhlbi.nih.gov; shenr@nhlbi.nih.gov; yyu@ncbi.nlm.nih.gov FU Intramural NIH HHS NR 40 TC 13 Z9 13 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD JUL 2 PY 2008 VL 3 BP 1 EP 16 AR 27 DI 10.1186/1745-6150-3-27 PG 16 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 333XG UT WOS:000258186300001 PM 18597684 ER PT J AU Oberst, MD Beberman, SJ Zhao, L Yin, JJ Ward, Y Kelly, K AF Oberst, Michael D. Beberman, Stacey J. Zhao, Liu Yin, Juan Juan Ward, Yvona Kelly, Kathleen TI TDAG51 is an ERK signaling target that opposes ERK-mediated HME16C mammary epithelial cell transformation SO BMC CANCER LA English DT Article ID GROWTH-FACTOR RECEPTOR; BREAST-CANCER; GENE-EXPRESSION; TYROSINE KINASE; DOWN-REGULATION; RAS; ACTIVATION; METASTASIS; APOPTOSIS; SURVIVAL AB Introduction: Signaling downstream of Ras is mediated by three major pathways, Raf/ERK, phosphatidylinositol 3 kinase (PI3K), and Ral guanine nucleotide exchange factor (RalGEF). Ras signal transduction pathways play an important role in breast cancer progression, as evidenced by the frequent over-expression of the Ras-activating epidermal growth factor receptors EGFR and ErbB2. Here we investigated which signal transduction pathways downstream of Ras contribute to EGFR-dependent transformation of telomerase-immortalized mammary epithelial cells HME16C. Furthermore, we examined whether a highly transcriptionally regulated ERK pathway target, PHLDA1 (TDAG51), suggested to be a tumor suppressor in breast cancer and melanoma, might modulate the transformation process. Methods: Cellular transformation of human mammary epithelial cells by downstream Ras signal transduction pathways was examined using anchorage-independent growth assays in the presence and absence of EGFR inhibition. TDAG51 protein expression was down-regulated by interfering small hairpin RNA (shRNA), and the effects on cell proliferation and death were examined in Ras pathway-transformed breast epithelial cells. Results: Activation of both the ERK and PI3K signaling pathways was sufficient to induce cellular transformation, which was accompanied by up-regulation of EGFR ligands, suggesting autocrine EGFR stimulation during the transformation process. Only activation of the ERK pathway was sufficient to transform cells in the presence of EGFR inhibition and was sufficient for tumorigenesis in xenografts. Up-regulation of the PHLDA1 gene product, TDAG51, was found to correlate with persistent ERK activation and anchorage-independent growth in the absence or presence of EGFR inhibition. Knockdown of this putative breast cancer tumor-suppressor gene resulted in increased ERK pathway activation and enhanced matrix-detached cellular proliferation of Ras/Raf transformed cells. Conclusion: Our results suggest that multiple Ras signal transduction pathways contribute to mammary epithelial cell transformation, but that the ERK signaling pathway may be a crucial component downstream of EGFR activation during tumorigenesis. Furthermore, persistent activation of ERK signaling up-regulates TDAG51. This event serves as a negative regulator of both Erk activation as well as matrix-detached cellular proliferation and suggests that TDAG51 opposes ERK-mediated transformation in breast epithelial cells. C1 [Oberst, Michael D.; Beberman, Stacey J.; Zhao, Liu; Yin, Juan Juan; Ward, Yvona; Kelly, Kathleen] NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Ward, Y (reprint author), NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, 37 Convent Dr,Room 1066, Bethesda, MD 20892 USA. EM michaeloberst@gmail.com; sjb115@gmail.com; caljimmy@gmail.com; yinjuan@mail.nih.gov; yward@helix.nih.gov; kellyka@mail.nih.gov FU Intramural NIH HHS NR 38 TC 20 Z9 20 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD JUL 2 PY 2008 VL 8 AR 189 DI 10.1186/1471-2407-8-189 PG 16 WC Oncology SC Oncology GA 332RM UT WOS:000258100800002 PM 18597688 ER PT J AU Colditz, GA Winn, DM AF Colditz, Graham A. Winn, Deborah M. TI Criteria for the evaluation of large cohort studies: An application to the Nurses' Health Study SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID CORONARY-HEART-DISEASE; RANDOMIZED CONTROLLED-TRIAL; BREAST-CANCER RISK; TYPE-2 DIABETES-MELLITUS; TRANS-FATTY-ACIDS; MIDDLE-AGED WOMEN; PHYSICAL-ACTIVITY; POSTMENOPAUSAL WOMEN; COLON-CANCER; LIFE-STYLE AB Evaluating the success of major funding programs from the National Institutes of Health (NIH) remains a vexing challenge. We propose a set of criteria to evaluate epidemiological studies that fit within the discovery, development, and delivery paradigm introduced by the NIH. We apply these criteria to the Nurses' Health Study (NHS), a large epidemiological cohort study initiated in the 1970s to evaluate the associations between oral contraceptives and risk of breast cancer and between diet and other lifestyle factors and risk of cancer overall. Our evaluation suggests that the NHS has led to important changes in health practice, and it underscores the need to develop metrics that are suitable to the evaluation of large epidemiological cohort studies. C1 [Colditz, Graham A.] Washington Univ, Sch Med, Dept Surg, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA. [Colditz, Graham A.] Barnes Jewish Hosp, St Louis, MO 63110 USA. [Winn, Deborah M.] NCI, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Colditz, GA (reprint author), Washington Univ, Sch Med, Dept Surg, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA. EM colditzg@wustl.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA89469, P01 CA087969] NR 101 TC 13 Z9 13 U1 2 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 2 PY 2008 VL 100 IS 13 BP 918 EP 925 DI 10.1093/jnci/djn193 PG 8 WC Oncology SC Oncology GA 322VJ UT WOS:000257403100006 PM 18577745 ER PT J AU Patel, AV Cheng, I Canzian, F Le Marchand, L Thun, MJ Berg, CD Buring, J Calle, EE Chanock, S Clavel-Chapelon, F Cox, DG Dorronsoro, M Dossus, L Haiman, CA Hankinson, SE Henderson, BE Hoover, R Hunter, DJ Kaaks, R Kolonel, LN Kraft, P Linseisen, J Lund, E Manjer, J McCarty, C Peeters, PHM Pike, MC Pollak, M Riboli, E Stram, DO Tjonneland, A Travis, RC Trichopoulos, D Tumino, R Yeager, M Ziegler, RG Feigelson, HS AF Patel, Alpa V. Cheng, Iona Canzian, Federico Le Marchand, Loic Thun, Michael J. Berg, Christine D. Buring, Julie Calle, Eugenia E. Chanock, Stephen Clavel-Chapelon, Francoise Cox, David G. Dorronsoro, Miren Dossus, Laure Haiman, Christopher A. Hankinson, Susan E. Henderson, Brian E. Hoover, Robert Hunter, David J. Kaaks, Rudolf Kolonel, Laurence N. Kraft, Peter Linseisen, Jakob Lund, Eiliv Manjer, Jonas McCarty, Catherine Peeters, Petra H. M. Pike, Malcolm C. Pollak, Michael Riboli, Elio Stram, Daniel O. Tjonneland, Anne Travis, Ruth C. Trichopoulos, Dimitrios Tumino, Rosario Yeager, Meredith Ziegler, Regina G. Feigelson, Heather Spencer TI IGF-1, IGFBP-1, and IGFBP-3 Polymorphisms Predict Circulating IGF Levels but Not Breast Cancer Risk: Findings from the Breast and Prostate Cancer Cohort Consortium (BPC3) SO PLOS ONE LA English DT Article AB IGF-1 has been shown to promote proliferation of normal epithelial breast cells, and the IGF pathway has also been linked to mammary carcinogenesis in animal models. We comprehensively examined the association between common genetic variation in the IGF1, IGFBP1, and IGFBP3 genes in relation to circulating IGF-1 and IGFBP-3 levels and breast cancer risk within the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). This analysis included 6,912 breast cancer cases and 8,891 matched controls (n = 6,410 for circulating IGF-1 and 6,275 for circulating IGFBP-3 analyses) comprised primarily of Caucasian women drawn from six large cohorts. Linkage disequilibrium and haplotype patterns were characterized in the regions surrounding IGF1 and the genes coding for two of its binding proteins, IGFBP1 and IGFBP3. In total, thirty haplotype-tagging single nucleotide polymorphisms (htSNP) were selected to provide high coverage of common haplotypes; the haplotype structure was defined across four haplotype blocks for IGF1 and three for IGFBP1 and IGFBP3. Specific IGF1 SNPs individually accounted for up to 5% change in circulating IGF-1 levels and individual IGFBP3 SNPs were associated up to 12% change in circulating IGFBP-3 levels, but no associations were observed between these polymorphisms and breast cancer risk. Logistic regression analyses found no associations between breast cancer and any htSNPs or haplotypes in IGF1, IGFBP1, or IGFBP3. No effect modification was observed in analyses stratified by menopausal status, family history of breast cancer, body mass index, or postmenopausal hormone therapy, or for analyses stratified by stage at diagnosis or hormone receptor status. In summary, the impact of genetic variation in IGF1 and IGFBP3 on circulating IGF levels does not appear to substantially influence breast cancer risk substantially among primarily Caucasian postmenopausal women. C1 [Patel, Alpa V.; Thun, Michael J.; Calle, Eugenia E.; Feigelson, Heather Spencer] Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. [Cheng, Iona] Univ Calif San Francisco, Inst Human Genet, Dept Epidemiol & Biostat, San Francisco, CA USA. [Canzian, Federico] German Canc Res Ctr, Genom Epidemiol Grp, Heidelberg, Germany. [Le Marchand, Loic; Kolonel, Laurence N.] Univ Hawaii, Canc Res Ctr, Epidemiol Program, Honolulu, HI USA. [Berg, Christine D.] NCI, Div Canc Prevent, Bethesda, MD USA. [Buring, Julie] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA USA. [Chanock, Stephen; Hoover, Robert; Yeager, Meredith] NCI, Core Genotyping Facil, Gaithersburg, MD USA. [Clavel-Chapelon, Francoise] Inst Gustave Roussy, INSERM, Villejuif, France. [Cox, David G.; Hunter, David J.; Kraft, Peter] Harvard Sch Publ Hlth, Epidemiol Dept, Program Mol & Genet Epidemiol, Boston, MA USA. [Dorronsoro, Miren] Dept Publ Hlth Guipuzcoa, San Sebastian, Spain. [Dossus, Laure; Kaaks, Rudolf; Linseisen, Jakob] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Haiman, Christopher A.; Henderson, Brian E.; Pike, Malcolm C.; Stram, Daniel O.] USC, Los Angeles, CA USA. [Hankinson, Susan E.] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Lund, Eiliv] Univ Tromso, Inst Community Med, Tromso, Norway. [Manjer, Jonas] Malmo Univ Hosp, Dept Surg, Malmo, Sweden. [McCarty, Catherine] Marshfield Clin Res Fdn, Ctr Human Genet, Marshfield, WI USA. [Peeters, Petra H. M.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [Pollak, Michael] McGill Univ, Dept Oncol, Montreal, PQ, Canada. [Peeters, Petra H. M.; Riboli, Elio] Imperial Coll, Dept Epidemiol & Publ Hlth, London, England. [Tjonneland, Anne] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. [Travis, Ruth C.] Univ Oxford, Canc Res UK Epidemiol Unit, Oxford, England. [Trichopoulos, Dimitrios] Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Tumino, Rosario] Canc Registry Azienda Ospedaliera Civile MP Arezzo, Ragusa, Italy. [Ziegler, Regina G.] NIH, NCI, DHHS, Div Canc Epidemiol & Genet, Bethesda, MD USA. RP Patel, AV (reprint author), Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. EM apatel@cancer.org RI Cox, David/A-2023-2009; Pollak, Michael/G-9094-2011; Dossus, Laure/B-2875-2013; Linseisen, Jakob/B-5353-2014; Clavel-Chapelon, Francoise/G-6733-2014 OI Cox, David/0000-0002-2152-9259; Pollak, Michael/0000-0003-3047-0604; Dossus, Laure/0000-0003-2716-5748; Linseisen, Jakob/0000-0002-9386-382X; FU National Cancer Institute [U01-CA98233, U01-CA98710, U01-CA98216, U01-CA98758]; Intramural Research Program of NIH/National Cancer Institute, Division of Cancer Epidemiology and Genetics. FX Grant support from National Cancer Institute cooperative agreements U01-CA98233, U01-CA98710, U01-CA98216, and U01-CA98758 and Intramural Research Program of NIH/National Cancer Institute, Division of Cancer Epidemiology and Genetics. NR 31 TC 78 Z9 79 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUL 2 PY 2008 VL 3 IS 7 AR e2578 DI 10.1371/journal.pone.0002578 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 406IM UT WOS:000263288200042 PM 18596909 ER PT J AU Wang, XH Tang, S Le, SY Lu, R Rader, JS Meyers, C Zheng, ZM AF Wang, Xiaohong Tang, Shuang Le, Shu-Yun Lu, Robert Rader, Janet S. Meyers, Craig Zheng, Zhi-Ming TI Aberrant Expression of Oncogenic and Tumor-Suppressive MicroRNAs in Cervical Cancer Is Required for Cancer Cell Growth SO PLOS ONE LA English DT Article AB MicroRNAs (miRNAs) play important roles in cancer development. By cloning and sequencing of a HPV16(+) CaSki cell small RNA library, we isolated 174 miRNAs (including the novel miR-193c) which could be grouped into 46 different miRNA species, with miR-21, miR-24, miR-27a, and miR-205 being most abundant. We chose for further study 10 miRNAs according to their cloning frequency and associated their levels in 10 cervical cancer- or cervical intraepithelial neoplasia-derived cell lines. No correlation was observed between their expression with the presence or absence of an integrated or episomal HPV genome. All cell lines examined contained no detectable miR-143 and miR-145. HPV-infected cell lines expressed a different set of miRNAs when grown in organotypic raft cultured as compared to monolayer cell culture, including expression of miR-143 and miR-145. This suggests a correlation between miRNA expression and tissue differentiation. Using miRNA array analyses for age-matched normal cervix and cervical cancer tissues, in combination with northern blot verification, we identified significantly deregulated miRNAs in cervical cancer tissues, with miR-126, miR-143, and miR-145 downregulation and miR-15b, miR-16, miR-146a, and miR-155 upregulation. Functional studies showed that both miR-143 and miR-145 are suppressive to cell growth. When introduced into cell lines, miR-146a was found to promote cell proliferation. Collectively, our data indicate that downregulation of miR-143 and miR- 145 and upregulation of miR-146a play a role in cervical carcinogenesis. C1 [Wang, Xiaohong; Tang, Shuang; Lu, Robert; Zheng, Zhi-Ming] NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Le, Shu-Yun] NIH, NCI, Ctr Canc Res, Nanobiol Program, Bethesda, MD USA. [Rader, Janet S.] Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO USA. [Meyers, Craig] Penn State Univ, Coll Med, Dept Microbiol & Immunol, Hershey, PA USA. RP Wang, XH (reprint author), NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM zhengt@exchange.nih.gov RI Tang, Shuang/F-9115-2014 OI Tang, Shuang/0000-0002-3084-0903 FU Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research [CA 94141, CA 95713, CA 79006] FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research and by NIH grants CA 94141 and CA 95713 to J.S.R. and CA 79006 to C.M. NR 75 TC 397 Z9 452 U1 5 U2 49 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUL 2 PY 2008 VL 3 IS 7 AR e2557 DI 10.1371/journal.pone.0002557 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 406IM UT WOS:000263288200024 PM 18596939 ER PT J AU Yu, K Wang, ZM Li, QZ Wacholder, S Hunter, DJ Hoover, RN Chanock, S Thomas, G AF Yu, Kai Wang, Zhaoming Li, Qizhai Wacholder, Sholom Hunter, David J. Hoover, Robert N. Chanock, Stephen Thomas, Gilles TI Population Substructure and Control Selection in Genome-Wide Association Studies SO PLOS ONE LA English DT Article AB Determination of the relevance of both demanding classical epidemiologic criteria for control selection and robust handling of population stratification ( PS) represents a major challenge in the design and analysis of genome-wide association studies (GWAS). Empirical data from two GWAS in European Americans of the Cancer Genetic Markers of Susceptibility (CGEMS) project were used to evaluate the impact of PS in studies with different control selection strategies. In each of the two original case-control studies nested in corresponding prospective cohorts, a minor confounding effect due to PS ( inflation factor lambda of 1.025 and 1.005) was observed. In contrast, when the control groups were exchanged to mimic a cost-effective but theoretically less desirable control selection strategy, the confounding effects were larger (lambda of 1.090 and 1.062). A panel of 12,898 autosomal SNPs common to both the Illumina and Affymetrix commercial platforms and with low local background linkage disequilibrium (pair-wise r(2)< 0.004) was selected to infer population substructure with principal component analysis. A novel permutation procedure was developed for the correction of PS that identified a smaller set of principal components and achieved a better control of type I error (to lambda of 1.032 and 1.006, respectively) than currently used methods. The overlap between sets of SNPs in the bottom 5% of p-values based on the new test and the test without PS correction was about 80%, with the majority of discordant SNPs having both ranks close to the threshold. Thus, for the CGEMS GWAS of prostate and breast cancer conducted in European Americans, PS does not appear to be a major problem in well-designed studies. A study using suboptimal controls can have acceptable type I error when an effective strategy for the correction of PS is employed. C1 [Yu, Kai; Wang, Zhaoming; Li, Qizhai; Wacholder, Sholom; Hunter, David J.; Hoover, Robert N.; Chanock, Stephen; Thomas, Gilles] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Wang, Zhaoming] Natl Canc Inst Frederick, SAIC Frederick Inc, Advanced Technol Program, Core Genotyping Facility, Frederick, MD USA. [Li, Qizhai] Chinese Acad Sci, Acad Math & Syst Sci, Beijing, Peoples R China. [Hunter, David J.] Harvard Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA USA. RP Yu, K (reprint author), NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. EM yuka@mail.nih.gov FU Intramural Research Program of the Division of Cancer Epidemiology and Genetics; Division of Cancer Prevention, National Cancer Institute, NIH, DHHS [N01-CO-12400]; US NIH [CA65725, CA87969, CA49449, CA67262, CA50385, 5UO1CA098233] FX The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. The Nurses' Health Studies (NHS) are supported by US NIH grants CA65725, CA87969, CA49449, CA67262, CA50385 and 5UO1CA098233. This project 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. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 35 TC 75 Z9 76 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUL 2 PY 2008 VL 3 IS 7 AR e2551 DI 10.1371/journal.pone.0002551 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 406IM UT WOS:000263288200019 PM 18596976 ER PT J AU Strebel, K Khan, MA AF Strebel, Klaus Khan, Mohammad A. TI APOBEC3G encapsidation into HIV-1 virions: which RNA is it? SO RETROVIROLOGY LA English DT Editorial Material ID VIRAL-RNA; 7SL RNA; PROTEIN; VIF AB APOBEC3G is a cytidine deaminase with potent antiviral activity. The protein deaminates singlestranded DNA but is known to bind cellular and viral RNAs. There is increasing evidence that RNA binding of APOBEC3G is important for packaging into viral particles. However, there is no consensus yet on the type of RNA involved. C1 [Strebel, Klaus; Khan, Mohammad A.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Strebel, K (reprint author), NIAID, Mol Microbiol Lab, NIH, 4-312, Bethesda, MD 20892 USA. EM kstrebel@niaid.nih.gov; Mkhan@niaid.nih.gov FU Intramural NIH HHS NR 10 TC 36 Z9 38 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD JUL 2 PY 2008 VL 5 AR 55 DI 10.1186/1742-4690-5-55 PG 2 WC Virology SC Virology GA 337XK UT WOS:000258468600002 PM 18597677 ER PT J AU Wong, FL Rotheram-Borus, MJ Lightfoot, M Pequegnat, W Comulada, WS Cumberland, W Weinhardt, LS Remien, RH Chesney, M Johnson, M AF Wong, F. Lennie Rotheram-Borus, Mary Jane Lightfoot, Marguerita Pequegnat, Willo Comulada, W. Scott Cumberland, William Weinhardt, Lance S. Remien, Robert H. Chesney, Margaret Johnson, Mallory CA Healthy Living Trial Grp TI Effects of behavioral intervention on substance use among people living with HIV: the Healthy Living Project randomized controlled study SO ADDICTION LA English DT Article DE HIV; intervention studies; randomized controlled trial; substance abuse; unprotected sex ID SEXUAL RISK BEHAVIORS; DRUG-USE; YOUNG-PEOPLE; UNITED-STATES; BISEXUAL MEN; PREVENTION; INFECTION; CARE; GAY AB Aim Reductions in substance use were examined in response to an intensive intervention with people living with human immunodeficiency virus (HIV) (PLH). Design, setting and participants A randomized controlled trial was conducted with 936 PLH who had recently engaged in unprotected sexual risk acts recruited from four US cities: Milwaukee, San Francisco, New York and Los Angeles. Substance use was assessed as the number of days of use of 19 substances recently (over the last 90 days), evaluated at 5-month intervals over 25 months. Intervention A 15-session case management intervention was delivered to PLH in the intervention condition; the control condition received usual care. Measurements An intention-to-treat analysis was conducted examining reductions on multiple indices of recent substance use calculated as the number of days of use. Findings Reductions in recent substance use were significantly greater for intervention PLH compared to control PLH: alcohol and/or marijuana use, any substance use, hard drug use and a weighted index adjusting for seriousness of the drug. While the intervention-related reductions in substance use were larger among women than men, men also reduced their use. Compared to controls, gay and heterosexual men in the intervention reduced significantly their use of alcohol and marijuana, any substance, stimulants and the drug severity-weighted frequency of use index. Gay men also reduced their hard drug use significantly in the intervention compared to the control condition. Conclusions A case management intervention model, delivered individually, is likely to result in significant and sustained reductions in substance use among PLH. C1 [Wong, F. Lennie; Rotheram-Borus, Mary Jane; Lightfoot, Marguerita; Comulada, W. Scott; Cumberland, William] Univ Calif Los Angeles, Los Angeles, CA USA. [Pequegnat, Willo] NIMH, Bethesda, MD 20892 USA. [Weinhardt, Lance S.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Remien, Robert H.] Columbia Univ, New York State Psychiat Inst, New York, NY USA. [Chesney, Margaret; Johnson, Mallory] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Rotheram-Borus, MJ (reprint author), 10920 Wilshire Blvd,Suite 350, Los Angeles, CA 90024 USA. EM rotheram@ucla.edu FU NIAID NIH HHS [P30 AI028697]; NIMH NIH HHS [U10MH057615, P30 MH043520, U10 MH057615, U10 MH057615-04, U10 MH057615-05, U10 MH057615-05S1, U10 MH057615-06, U10 MH057615-07, U10 MH057616, U10 MH057631, U10 MH057636, U10MH057616, U10MH057631, U10MH057636] NR 40 TC 17 Z9 17 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0965-2140 J9 ADDICTION JI Addiction PD JUL PY 2008 VL 103 IS 7 BP 1206 EP 1214 DI 10.1111/j.1360-0443.2008.02222.x PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 312PX UT WOS:000256684400023 PM 18494840 ER PT J AU Caceres, CF Konda, KA Salazar, X Leon, SR Klausner, JD Lescano, AG Maiorana, A Kegeles, S Jones, FR Coates, TJ AF Caceres, Carlos F. Konda, Kelika A. Salazar, Ximena Leon, Segundo R. Klausner, Jeffrey D. Lescano, Andres G. Maiorana, Andre Kegeles, Susan Jones, Franca R. Coates, Thomas J. CA NIMH HIV STD Collaborative Interve TI New populations at high risk of HIV/STIs in low-income, urban coastal Peru SO AIDS AND BEHAVIOR LA English DT Article DE HIV epidemiology; MSM; sexual behavior; risk; community intervention trial; vulnerability ID COMMERCIAL SEX WORKERS; LATIN-AMERICA; HIV; MEN; BEHAVIOR; GAY; INTERVENTION; INFECTION; EPIDEMIC; HIV/AIDS AB The HIV epidemic in Peru is concentrated primarily among men who have sex with men. HIV interventions have focused exclusively on a narrowly defined group of MSM and FSW to the exclusion of other populations potentially at increased risk. Interventions targeting MSM and FSW are insufficient and there is evidence that focusing prevention efforts solely on these populations may ignore others that do not fall directly into these categories. This paper describes non-traditional, vulnerable populations within low-income neighborhoods. These populations were identified through the use of ethnographic and epidemiologic formative research methods and the results are reported in this publication. Although the traditional vulnerable groups are still in need of prevention efforts, this study provides evidence of previously unrecognized populations at increased risk that should also receive attention from HIV/STI prevention programs. C1 [Caceres, Carlos F.; Salazar, Ximena; Leon, Segundo R.; Lescano, Andres G.] Cayetano Heredia Univ, Sch Publ Hlth, Miraflores, Peru. [Klausner, Jeffrey D.; Maiorana, Andre; Kegeles, Susan] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Caceres, Carlos F.; Konda, Kelika A.; Coates, Thomas J.] Univ Calif Los Angeles, Los Angeles, CA USA. [Lescano, Andres G.; Jones, Franca R.] USN, Med Res Ctr Detachment, Lima, Peru. [NIMH HIV STD Collaborative Interve] NIMH, Rockville, MD 20857 USA. RP Caceres, CF (reprint author), Cayetano Heredia Univ, Sch Publ Hlth, Av Armendariz 445,Lima 18, Miraflores, Peru. EM ccaceres@upch.edu.pe RI Lescano, Andres/B-8479-2008; OI Lescano, Andres/0000-0001-9779-633X; Caceres, Carlos/0000-0002-8101-0790 FU FIC NIH HHS [D43 TW007393, D43 TW007393-06]; NIMH NIH HHS [2U10 MH 061536, R01 MH078752, U10 MH061536] NR 30 TC 22 Z9 23 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS behav. PD JUL PY 2008 VL 12 IS 4 BP 544 EP 551 DI 10.1007/s10461-007-9348-y PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 315VJ UT WOS:000256908000002 PM 18161019 ER PT J AU Tao, W Richards, C Hamer, D AF Tao, Wang Richards, Chris Hamer, Dean TI Short communication - Enhancement of HIV infection by cellulose sulfate SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PHASE-I SAFETY; ANTIBODY-MEDIATED ENHANCEMENT; VAGINAL GEL; SOLUBLE CD4; MICROBICIDES; ACCEPTABILITY; GLYCOPROTEIN; ATTACHMENT; PREVENTION AB Cellulose sulfate, a polyanionic compound derived from cotton, has been proposed as a topical microbicide to reduce the sexual transmission of HIV. However, a phase III clinical trial of a vaginal gel formulation of cellulose sulfate (Ushercell) had to be prematurely closed after early data indicated microbicide users had a higher rate of HIV infection than women using a placebo. The unexpected results of the cellulose sulfate trail prompted us to reexamine and attempt to replicate the available preclinical data for this compound and other polyanions. We show here that cellulose sulfate has a biphasic effect on HIV infection in vitro: at high concentrations it inhibits infection but at low concentrations it significantly and reproducibly increases HIV infection. This stimulatory effect is evident for the R5-tropic strains of virus responsible for sexual transmission, reflects the rate of infection rather than viral growth, and occurs at clinically relevant concentrations of the compound. An examination of published studies shows that the biphasic effect of cellulose sulfate was evident in previous research by independent laboratories and is also found for other polyanions such as dextrin sulfate and PRO2000. These data help in understanding the failure of the Ushercell clinical trial and indicate that cellulose sulfate is not safe for mucosal application in humans. C1 [Tao, Wang; Richards, Chris; Hamer, Dean] NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA. RP Hamer, D (reprint author), NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA. EM deanh@helix.nih.gov NR 26 TC 50 Z9 51 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUL PY 2008 VL 24 IS 7 BP 925 EP 929 DI 10.1089/aid.2008.0043 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 335PH UT WOS:000258302000005 PM 18627218 ER PT J AU Schwandt, ML Higley, JD Suomi, SJ Heilig, M Barr, CS AF Schwandt, Melanie L. Higley, James D. Suomi, Stephen J. Heilig, Markus Barr, Christina S. TI Rapid tolerance and locomotor sensitization in ethanol-naive adolescent rhesus macaques SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol response; tolerance; sensitization; nonhuman primate; adolescence ID EXCESSIVE ALCOHOL-CONSUMPTION; TRANSPORTER GENE VARIATION; CSF MONOAMINE METABOLITE; NONHUMAN PRIMATE MODEL; NONDRINKER UCHA RATS; LOW-DOSE ETHANOL; BEHAVIORAL SENSITIZATION; INITIAL SENSITIVITY; GENDER-DIFFERENCES; MACACA-MULATTA AB Background: Acute and chronic tolerance, as well as locomotor sensitization, have been linked to ethanol intake. This study examined the change in response between 2 acutely administered doses of ethanol in adolescent rhesus macaques, with the objective of investigating rapid tolerance and locomotor sensitization to the behavioral effects of ethanol, and whether these phenomena are related to voluntary ethanol consumption in nonhuman primates. Methods: Rhesus macaques (n = 109, 42 males, 67 females) were administered 2 sequential intravenous doses of ethanol (2.2 g/kg for males, 2.0 g/kg for females) separated by a period of 5 to 30 days. Following each injection, subjects underwent a 30-minute behavior assessment. Behavioral data were summarized using factor analysis, and compared between the 2 doses using repeated measures ANOVA. The relationship between behavioral response measures and the number of days between doses was analyzed using regression analyses. Following the second ethanol dose, subjects were given free access to an aspartame-sweetened 8.4% ethanol solution for 1 hour a day for 4 weeks. Percent change in behavioral response measures from dose 1 to dose 2 was analyzed for associations with ethanol consumption using multiple regression analyses. Results: Factor analysis yielded 3 factors: ataxia, stimulation, and jumping. From dose 1 to dose 2 there was a significant decrease in ataxia and a significant increase in stimulation. Peak blood ethanol concentration did not differ between doses. There were no significant associations between the number of days between doses and the magnitude of change in response for any of the behavioral measures. Percent change in stimulation from dose 1 to dose 2 was positively associated with subsequent oral ethanol consumption only in females tested in a social setting. Conclusions: Adolescent rhesus macaques develop rapid tolerance to the motor-impairing effects of alcohol, while at the same time developing locomotor sensitization. These changes in response are not necessarily short lived, and may persist for some time following the first ethanol dose. Clear and consistent associations between rapid tolerance and locomotor sensitization and ethanol intake levels have yet to be demonstrated, however. C1 [Schwandt, Melanie L.; Heilig, Markus; Barr, Christina S.] NIAAA, Lab Clin & Translat Studies, NIH, NIH Anim Ctr, Poolesville, MD 20837 USA. [Higley, James D.] Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA. [Suomi, Stephen J.] NICHHD, Comparat Ethol Lab, NIH, NIH Anim Ctr, Poolesville, MD 20837 USA. RP Schwandt, ML (reprint author), NIAAA, Lab Clin & Translat Studies, NIH, NIH Anim Ctr, POB 529, Poolesville, MD 20837 USA. EM melanies@mail.nih.gov RI Schwandt, Melanie/L-9866-2016 NR 89 TC 8 Z9 8 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUL PY 2008 VL 32 IS 7 BP 1217 EP 1228 DI 10.1111/j.1530-0277.2008.00676.x PG 12 WC Substance Abuse SC Substance Abuse GA 326XK UT WOS:000257692600013 PM 18482160 ER PT J AU O'Malley, SS Robin, RW Levenson, AL Wolf, IG Chance, LE Hodgkinson, CA Romano, D Robinson, J Meandzija, B Stillner, V Wu, R Goldman, D AF O'Malley, Stephanie S. Robin, Robert W. Levenson, Aryeh L. Wolf, Iva Grey Chance, Lawrence E. Hodgkinson, Colin A. Romano, Denise Robinson, Jane Meandzija, Boris Stillner, Verner Wu, Ran Goldman, David TI Naltrexone alone and with sertraline for the treatment of alcohol dependence in Alaska Natives and non-natives residing in rural settings: A randomized controlled trial SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol dependence; naltrexone; Alaska Natives; minorities; rural ID MU-OPIOID-RECEPTOR; POSTTRAUMATIC-STRESS-DISORDER; COMBINED PHARMACOTHERAPIES; BEHAVIORAL INTERVENTIONS; BETA-ENDORPHIN; UNITED-STATES; MENTAL-HEALTH; PRIMARY-CARE; LOW-RISK; DRINKING AB Background: Access to specialty alcoholism treatment in rural environments is limited and new treatment approaches are needed. The objective was to evaluate the efficacy of naltrexone alone and in combination with sertraline among Alaska Natives and other Alaskans living in rural settings. An exploratory aim examined whether the Asn40Asp polymorphism of the mu-opioid receptor gene (OPRM1) predicted response to naltrexone, as had been reported in Caucasians. Methods: Randomized, controlled trial enrolling 101 Alaskans with alcohol dependence, including 68 American Indians/Alaska Natives. Participants received 16 weeks of either (1) placebo (placebo naltrexone + placebo sertraline), (2) naltrexone monotherapy (50 mg naltrexone + sertraline placebo) and (3) naltrexone + sertraline (100 mg) plus nine sessions of medical management and supportive advice. Primary outcomes included Time to First Heavy Drinking Day and Total Abstinence. Results: Naltrexone monotherapy demonstrated significantly higher total abstinence (35%) compared with placebo (12%, p = 0027) and longer, but not statistically different, Time to First Heavy Drinking Day (p = 0.093). On secondary measures, naltrexone compared with placebo demonstrated significant improvements in percent days abstinent (p = 0.024) and drinking-related consequences (p = 0.02). Combined sertraline and naltrexone did not differ from naltrexone alone. The pattern of findings was generally similar for the American Indian/Alaska Native subsample. Naltrexone treatment response was significant within the group of 75 individuals who were homozygous for OPRM1 Asn40 allele. There was a small number of Asp40 carriers, precluding statistical testing of the effect of this allele on response. Conclusions: Naltrexone can be used effectively to treat alcoholism in remote and rural communities, with evidence of benefit for American Indians and Alaska Natives. New models of care incorporating pharmacotherapy could reduce important health disparities related to alcoholism. C1 [O'Malley, Stephanie S.; Robin, Robert W.; Romano, Denise; Robinson, Jane; Meandzija, Boris; Wu, Ran] Yale Univ, Sch Med, Connecticut Mental Hlth Ctr, New Haven, CT 06519 USA. [Hodgkinson, Colin A.; Goldman, David] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. RP O'Malley, SS (reprint author), Yale Univ, Sch Med, Connecticut Mental Hlth Ctr, S202,34 Pk St, New Haven, CT 06519 USA. EM stephanie.omalley@yale.edu RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; GreyWolf, Iva/0000-0001-5812-2287 FU Intramural NIH HHS [Z01 AA000306-02]; NIAAA NIH HHS [K05 AA014715, KO5AA014715, R01 AA012028, R01AA12028] NR 89 TC 35 Z9 35 U1 3 U2 16 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUL PY 2008 VL 32 IS 7 BP 1271 EP 1283 DI 10.1111/j.1530-0277.2008.00682.x PG 13 WC Substance Abuse SC Substance Abuse GA 326XK UT WOS:000257692600018 PM 18482155 ER PT J AU Griffin-Pierce, T Silverberg, N Connor, D Jim, M Peters, J Kaszniak, A Sabbagh, MN AF Griffin-Pierce, Trudy Silverberg, Nina Connor, Donald Jim, Mirmie Peters, Jill Kaszniak, Alfred Sabbagh, Marwan N. TI Challenges to the recognition and assessment of Alzheimer's disease in American Indians of the southwestern United States SO ALZHEIMERS & DEMENTIA LA English DT Article DE American Indian; Alzheimer's disease; elder health research; mental status ID DEMENTIA RATING-SCALE; BOSTON NAMING TEST; AFRICAN-AMERICANS; NATIVE-AMERICANS; NORMATIVE DATA; MENTAL-HEALTH; NORMS; PERFORMANCE; ELDERS; CAREGIVERS AB Little is known about Alzheimer's disease (AD) and related neurodegenerative diseases in American Indian (AI) populations. To provide appropriate health care to elder AIs, whose population is expected to increase dramatically during the next 50 years, it is imperative to attain a better understanding of the interaction of culture and disease in this underserved population. Raising awareness in the AI population regarding the nature of dementia as it compares to normal aging and the development of culturally appropriate instruments to detect and stage AD are essential for future health care efforts. Barriers restricting clinical service to this population include historical factors relating to access to health care, cultural beliefs regarding aging, demographic diversity of the population, competing epidemiologic risk factors, and lack of proper assessment tools for clinicians. (C) 2008 The Alzheimer's Association. All rights reserved. C1 [Griffin-Pierce, Trudy; Kaszniak, Alfred] Univ Arizona, Dept Anthropol, Tucson, AZ 85721 USA. [Griffin-Pierce, Trudy; Kaszniak, Alfred] Univ Arizona, Dept Psychol, Tucson, AZ 85721 USA. [Silverberg, Nina] NIA, Bethesda, MD 20892 USA. [Connor, Donald; Jim, Mirmie; Sabbagh, Marwan N.] Sun Hlth Res Inst, Cleo Roberts Ctr Clin Res, Sun City, AZ USA. [Peters, Jill] Translat Genom Res Inst, Phoenix, AZ USA. RP Griffin-Pierce, T (reprint author), Univ Arizona, Dept Anthropol, Tucson, AZ 85721 USA. EM trudyg@email.arizona.edu FU NIA NIH HHS [P30 AG019610, P30 AG019610-089003, P30-AG019610] NR 74 TC 8 Z9 9 U1 3 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JUL PY 2008 VL 4 IS 4 BP 291 EP 299 DI 10.1016/j.jalz.2007.10.012 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 326NC UT WOS:000257665200010 PM 18631981 ER PT J AU Parikh, NI Hwang, SJ Larson, MG Levy, D Fox, CS AF Parikh, Nisha I. Hwang, Shih-Jen Larson, Martin G. Levy, Daniel Fox, Caroline S. TI Chronic kidney disease as a predictor of cardiovascular disease (from the Framingham Heart Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID PRIOR MYOCARDIAL-INFARCTION; GLOMERULAR-FILTRATION-RATE; HIGH BLOOD-PRESSURE; SERUM CREATININE; RISK-FACTORS; US ADULTS; RENAL-INSUFFICIENCY; UNITED-STATES; PREVALENCE; MORTALITY AB Chronic kidney disease (CKD) is a risk factor for cardiovascular disease (CVD), although shared risk factors may mediate much of the association. CKD and CVD were related in the setting of specific CVD risk factors, and whether more advanced CKD was a CVD risk equivalent was determined. The Framingham Heart Study original cohort (n = 2,471, mean age 68 years, 58.9% women) was studied. Glomerular filtration rate was estimated (eGFR) using the simplified Modification of Diet in Renal Disease Study equation. CKD was defined as eGFR <59 (women) and <64 ml/min/1.73 m(2) (men), and stage 3b CKD was defined as eGFR of 30 to 44,(women) and 30 to 50 ml/min/1.73 m(2) (men). Cox proportional hazard models adjusting for CVD risk factors were used to relate CKD to CVD. Effect modification by CVD risk factors was tested for. Overall, 23.2% of the study sample had CKD (n = 574, mean eGFR 50 ml/min/1.73 m(2)) and 5.3% had stage 3b CKD (n = 131, mean eGFR 42 ml/min/1.73 m(2)). In multivariable models (mean follow-up 16 years), stage 3 CKD was marginally associated with CVD (hazard ratio [HR] 1.17, 95% confidence interval [CI] 0.99 to 1.38, p = 0.06), whereas stage 3b CKD was associated with CVD (HR 1.41, 95% CI 1.05 to 1.91, p = 0.02). Testing CVD risk equivalency, the risk of CVD for stage 3b CKD in subjects with previous CVD was significantly lower compared with subjects with previous CVD and no stage 3b CKD (age- and sex-adjusted HR for CVD 0.66, 95% CI 0.47 to 0.91, p = 0.01). Low high-density lipoprotein cholesterol modified the association between CKD and CVD (p = 0.004 for interaction). Stage 3b CKD was associated with CVD, but was not a CVD risk equivalent. In conclusion, CVD risk in the setting of CKD is higher in the setting of low high-density lipoprotein cholesterol. (C) 2008 Elsevier Inc. All rights reserved. C1 [Parikh, Nisha I.; Hwang, Shih-Jen; Larson, Martin G.; Levy, Daniel; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Hwang, Shih-Jen; Levy, Daniel; Fox, Caroline S.] NHLBI, NIH, Bethesda, MD 20892 USA. [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Endocrinol, Boston, MA 02115 USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA. EM foxca@nhlbi.nih.gov OI Larson, Martin/0000-0002-9631-1254 FU NHLBI NIH HHS [N01 HC025195, N01-HC-25195, N01HC25195] NR 27 TC 48 Z9 51 U1 1 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUL 1 PY 2008 VL 102 IS 1 BP 47 EP 53 DI 10.1016/j.amjcard.2008.02.095 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 321JG UT WOS:000257300100008 PM 18572034 ER PT J AU Neuhouser, ML Sorensen, B Hollis, BW Ambs, A Ulrich, CM McTiernan, A Bernstein, L Wayne, S Gilliland, F Baumgartner, K Baumgartner, R Ballard-Barbash, R AF Neuhouser, Marian L. Sorensen, Bess Hollis, Bruce W. Ambs, Anita Ulrich, Cornelia M. McTiernan, Anne Bernstein, Leslie Wayne, Sharon Gilliland, Frank Baumgartner, Kathy Baumgartner, Richard Ballard-Barbash, Rachel TI Vitamin D insufficiency in a multiethnic cohort of breast cancer survivors SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID PROSTATE-CANCER; LUNG-CANCER; D ANALOGS; 1-ALPHA,25-DIHYDROXYVITAMIN D-3; SERUM CONCENTRATIONS; DIETARY-INTAKE; 25-HYDROXYVITAMIN-D; RISK; PREVENTION; RECEPTOR AB Background: Little is known about vitamin D status in breast cancer survivors. This issue is important because vitamin D influences pathways related to carcinogenesis. Objective: The objective of this report was to describe and understand vitamin D status in a breast cancer survivor cohort. Design: Data are from the Health, Eating, Activity, and Lifestyle study. With the use of a cross-sectional design, we examined serum concentrations of 25-hydroxyvitamin D [25(OH)D] in 790 breast cancer survivors from western Washington state, New Mexico, and Los Angeles County. Cancer treatment data were obtained from Surveillance, Epidemiology, and End Results registries and medical records. Fasting blood, anthropometry, and lifestyle habits were collected after diagnosis and treatment. We examined distributions of 25(OH)D by race-ethnicity, season, geography, and clinical characteristics. Multivariate regression tested associations between 25(OH)D and stage of disease. Results: Five hundred ninety-seven (75.6%) of the women had low serum 25(OH)D, suggesting vitamin D insufficiency or frank deficiency. The overall mean (+/- SD) was 24.8 +/- 10.4 ng/mL, but it was lower for African Americans (18.1 +/- 8.7 ng/mL) and Hispanics (22.1 +/- 9.2 ng/mL). Women with localized (n = 424) or regional (n = 182) breast cancer had lower serum 25(OH)D than did women with in situ disease (n = 184) (P = 0.05 and P = 0.03, respectively). Multivariate regression models controlled for age, body mass index (in kg/m(2)), race-ethnicity, geography, season, physical activity, diet, and cancer treatments showed that stage of disease independently predicted serum 25(OH)D (P = 0.02). Conclusions: In these breast cancer survivors, the prevalence of vitamin D insufficiency was high. Clinicians might consider monitoring vitamin D status in breast cancer patients, together with appropriate treatments, if necessary. C1 [Neuhouser, Marian L.; Sorensen, Bess; Ulrich, Cornelia M.; McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98109 USA. [Hollis, Bruce W.] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. [Ambs, Anita; Ballard-Barbash, Rachel] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Bernstein, Leslie; Gilliland, Frank] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [Bernstein, Leslie; Gilliland, Frank] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Bernstein, Leslie] City Hope Canc Natl Med Ctr, Div Populat Sci, Duarte, CA USA. [Wayne, Sharon] Univ New Mexico, New Mexico Tumor Registry, Albuquerque, NM 87131 USA. [Baumgartner, Kathy; Baumgartner, Richard] Univ Louisville, Dept Epidemiol & Populat Hlth, Sch Publ Hlth & Informat Sci, Louisville, KY 40292 USA. RP Neuhouser, ML (reprint author), Fred Hutchinson Canc Res Ctr, Canc Prevent Program, 1100 Fairview Ave N,M4-B402,POB 19024, Seattle, WA 98109 USA. EM mneuhous@fhcrc.org FU NCI NIH HHS [N01 CN005228, N01 PC035138-22, N01-CN-05228, N01-CN-75036-20, N01-PC-35138, N01-PC-35139, N01-PC-35142, N01-PC-67007, N01-PC-67009, N01-PC-67010, N01PC35138, N01PC35139, N01PC35142, T32 CA009661, T32 CA09661]; NCRR NIH HHS [M01 RR000037]; NICHD NIH HHS [N01-HD-3-3175] NR 46 TC 69 Z9 69 U1 1 U2 10 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUL PY 2008 VL 88 IS 1 BP 133 EP 139 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 326FH UT WOS:000257643300018 PM 18614733 ER PT J AU Flood, A Rastogi, T Wirfalt, E Mitrou, PN Reedy, J Subar, AF Kipnis, V Mouw, T Hollenbeck, AR Leitzmann, M Schatzkin, A AF Flood, Andrew Rastogi, Tanuja Wirfaelt, Elisabet Mitrou, Panagiota N. Reedy, Jill Subar, Amy F. Kipnis, Victor Mouw, Traci Hollenbeck, Albert R. Leitzmann, Michael Schatzkin, Arthur TI Dietary patterns as identified by factor analysis and colorectal cancer among middle-aged Americans SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRES; COLON-CANCER; PROSPECTIVE COHORT; UNITED-STATES; RISK-FACTORS; MEAT CONSUMPTION; RECTAL-CANCER; WOMEN; FRUIT; VEGETABLES AB Background: Although diet has long been suspected as an etiological factor for colorectal cancer, studies of single foods and nutrients have provided inconsistent results. Objective: We used factor analysis methods to study associations between dietary patterns and colorectal cancer in middle-aged Americans. Design: Diet was assessed among 293 615 men and 198 767 women in the National Institutes of Health-AARP Diet and Health Study. Principal components factor analysis identified 3 primary dietary patterns: a fruit and vegetables, a diet foods, and a red meat and potatoes pattern. State cancer registries identified 2151 incident cases of colorectal cancer in men and 959 in women between 1995 and 2000. Results: Men with high scores on the fruit and vegetable pattern were at decreased risk [relative risk (RR) for quintile (Q) 5 versus Q1: 0.8 1; 95% CI: 0.70, 0.93; P for trend = 0.004]. Both men and women had a similar risk reduction with high scores on the diet food factor: men (RR: 0.82; 95% CI: 0.72, 0.94; P for trend = 0.001) and women (RR: 0.87; 95% CI: 0.71, 1.07; P for trend = 0.06). High scores on the red meat factor were associated with increased risk: men (RR: 1.17; 95% CI: 1.02,1.35; P for trend = 0.14) and women (RR: 1.48; 95% CI: 1.20, 1.83; P for trend = 0.0002). Conclusions: These results suggest that dietary patterns characterized by a low frequency of meat and potato consumption and frequent consumption of fruit and vegetables and fat-reduced foods are consistent with a decreased risk of colorectal cancer. C1 [Flood, Andrew] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA. [Flood, Andrew] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN 55454 USA. [Rastogi, Tanuja; Leitzmann, Michael; Schatzkin, Arthur] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Wirfaelt, Elisabet] Lund Univ, Dept Clin Sci, Malmo, Sweden. [Mitrou, Panagiota N.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Reedy, Jill; Subar, Amy F.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Kipnis, Victor] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Mouw, Traci] Univ London Imperial Coll Sci Technol & Med, Div Epidemiol Publ Hlth & Primary Care, London, England. [Hollenbeck, Albert R.] AARP, Environm Anal Dept, Washington, DC USA. RP Flood, A (reprint author), Univ Minnesota, Div Epidemiol & Community Hlth, 1300 S 2nd St,Suite 300, Minneapolis, MN 55454 USA. EM flood@epi.umn.edu FU Intramural NIH HHS; NCI NIH HHS [K07 CA108910, K07 CA108910-01A1] NR 42 TC 70 Z9 72 U1 2 U2 7 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUL PY 2008 VL 88 IS 1 BP 176 EP 184 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 326FH UT WOS:000257643300024 PM 18614739 ER PT J AU Galgano, MT Castle, PE Stoler, MH Solomon, D Schiffman, M AF Galgano, Mary T. Castle, Philip E. Stoler, Mark H. Solomon, Diane Schiffman, Mark TI Can HPV-16 genotyping provide a benchmark for cervical biopsy specimen interpretation? SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE cervical intraepithelial neoplasia; human papillomavirus; HPV; colposcopy; biopsy; quality assurance; benchmark ID HUMAN-PAPILLOMAVIRUS DNA; ATYPICAL SQUAMOUS-CELLS; ASCUS-LSIL TRIAGE; HIGH-RISK HPV; INTRAEPITHELIAL NEOPLASIA GRADE-2; UNDETERMINED SIGNIFICANCE; MANAGEMENT STRATEGIES; RANDOMIZED-TRIAL; FOLLOW-UP; CANCER AB Human papillomavirus (HPV) detection is an objective quality assurance benchmark for cervical cytology. There is no comparable metric for cervical biopsies despite biopsies having similar interobserver variability. Because HPV-16 positivity increases with the severity of cervical abnormality, we explored whether HPV-16 detection might be a useful metric for distinguishing a diagnosis of less than cervical intraepithelial neoplasia (CIN) 2 from CIN 2 or worse (representing the clinical threshold for treatment). By using Atypical Squamous Cells of Undetermined Significance-Low-Grade Squamous Intraepithelial Lesion Triage Study data, we compared biopsy diagnoses of the 10 clinical center (CC) pathologists with the quality control (QC) group. Although the percentage of HPV-16 correlated with. severity of diagnoses, there was great variability between the rates for each individual CC pathologist. Agreement between individual CC pathologists and the QC group on the percentage of CIN 2 or worse containing HPV-16 correlated weakly with agreement on whether the diagnosis was less than CIN 2 or CIN 2 or worse. Thus the HPV-16 fraction was not found to be broadly useful as a quality assurance metric for biopsy diagnosis in this analysis. C1 [Galgano, Mary T.; Stoler, Mark H.] Univ Virginia Hlth Syst, Dept Pathol, Robert E Fechner Lab Surg Pathol, Charlottesville, VA 22908 USA. [Castle, Philip E.; Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Solomon, Diane] NCI, Canc Prevent Div, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Stoler, MH (reprint author), Univ Virginia Hlth Syst, Dept Pathol, Robert E Fechner Lab Surg Pathol, 1215 Lee St,HEp Off 3032, Charlottesville, VA 22908 USA. FU Intramural NIH HHS; NCI NIH HHS [CN-55158, CN-55157, CN-55155, CN-55105, CN-55154, CN-55159, CN-55156, CN-55153] NR 26 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JUL PY 2008 VL 130 IS 1 BP 65 EP 70 DI 10.1309/A8MFC18TWANC8QFH PG 6 WC Pathology SC Pathology GA 315RL UT WOS:000256897000008 PM 18550472 ER PT J AU Reedy, J Mitrou, PN Krebs-Smith, SM Wirfalt, E Flood, A Kipnis, V Leitzmann, M Mouw, T Hollenbeck, A Schatzkin, A Subar, AF AF Reedy, J. Mitrou, P. N. Krebs-Smith, S. M. Wirfalt, E. Flood, A. Kipnis, V. Leitzmann, M. Mouw, T. Hollenbeck, A. Schatzkin, A. Subar, A. F. TI Index-based dietary patterns and risk of colorectal cancer SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE colorectal neoplasms; food habits; risk ID MAJOR CHRONIC DISEASE; FOOD-FREQUENCY QUESTIONNAIRE; GUIDELINES-FOR-AMERICANS; PROSPECTIVE COHORT; MEDITERRANEAN DIET; QUALITY; MORTALITY; WOMEN; ADHERENCE; SURVIVAL AB The authors compared how four indexes-the Healthy Eating Index-2005, Alternate Healthy Eating Index, Mediterranean Diet Score, and Recommended Food Score-are associated with colorectal cancer in the National Institutes of Health-AARP Diet and Health Study (n = 492,382). To calculate each score, they merged data from a 124-item food frequency questionnaire completed at study entry (1995-1996) with the MyPyramid Equivalents Database (version 1.0). Other variables included energy, nutrients, multivitamins, and alcohol. Models were stratified by sex and adjusted for age, ethnicity, education, body mass index, smoking, physical activity, and menopausal hormone therapy (in women). During 5 years of follow-up, 3,110 incident colorectal cancer cases were ascertained. Although the indexes differ in design, a similarly decreased risk of colorectal cancer was observed across all indexes for men when comparing the highest scores with the lowest: Healthy Eating Index-2005 (relative risk (RR) = 0.72, 95% confidence interval (CI): 0.62, 0.83); Alternate Healthy Eating Index (RR = 0.70, 95% CI: 0.61, 0.81); Mediterranean Diet Score (RR = 0.72, 95% CI: 0.63, 0.83); and Recommended Food Score (RR = 0.75, 95% CI: 0.65, 0.87). For women, a significantly decreased risk was found with the Healthy Eating Index-2005, although Alternate Healthy Eating Index results were similar. Index-based dietary patterns that are consistent with given dietary guidelines are associated with reduced risk. C1 [Reedy, J.] NCI, Div Canc Control & Populat Sci, Appl Res Program, Risk Factor Monitoring & Methods Branch, Bethesda, MD 20892 USA. [Mitrou, P. N.] Univ Cambridge, Cambridge, England. [Mitrou, P. N.] World Canc Res Fund, London, England. [Wirfalt, E.] Lund Univ, Malmo, Sweden. [Flood, A.] Univ Minnesota, Minneapolis, MN USA. [Mouw, T.] Univ London Imperial Coll Sci Technol & Med, London, England. [Hollenbeck, A.] AARP, Washington, DC USA. RP Reedy, J (reprint author), NCI, Div Canc Control & Populat Sci, Appl Res Program, Risk Factor Monitoring & Methods Branch, MSC 7344,EPN 4005,6130 Execut Blvd, Bethesda, MD 20892 USA. EM reedyj@mail.nih.gov FU Intramural NIH HHS NR 32 TC 123 Z9 125 U1 2 U2 14 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUL 1 PY 2008 VL 168 IS 1 BP 38 EP 48 DI 10.1093/aje/kwn097 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 316VC UT WOS:000256976800006 PM 18525082 ER PT J AU Parascandola, M Hurd, AL Augustson, E AF Parascandola, Mark Hurd, Ami L. Augustson, Erik TI Consumer awareness and attitudes related to new potential reduced-exposure tobacco products SO AMERICAN JOURNAL OF HEALTH BEHAVIOR LA English DT Article DE tobacco; PREP; consumer survey; technology; personal health ID HARM REDUCTION; CIGARETTES; PREPS AB Objective: To assess US consumers' awareness of potential reduced-exposure tobacco products (PREPs) and correlates of interest in these products. Methods: A representative sample of 9736 US consumers who had responded to a previous marketing survey were queried in 2005. Results: Among current smokers, interest in PREPs was high (77.3%) and was associated with concern about personal health as well as favorable attitudes towards technology and a willingness to experiment with new products and trends. Conclusions: These results suggest that interest in PREPs may reflect a range of consumer preferences beyond expectations of health benefit. C1 [Parascandola, Mark; Augustson, Erik] NCI, Tobacco Control Res Branch, Bethesda, MD 20892 USA. [Hurd, Ami L.] Sharp HealthCare, Strateg Planning Dept, San Diego, CA USA. RP Parascandola, M (reprint author), NCI, Tobacco Control Res Branch, 6130 Execut Blvd,Room 4039, Bethesda, MD 20892 USA. EM paramark@mail.nih.gov FU NCI NIH HHS [N02-PC-54418, N01-CO-12400] NR 17 TC 10 Z9 10 U1 0 U2 1 PU PNG PUBLICATIONS PI STAR CITY PA PO BOX 4593, STAR CITY, WV 26504-4593 USA SN 1087-3244 J9 AM J HEALTH BEHAV JI Am. J. Health Behav. PD JUL-AUG PY 2008 VL 32 IS 4 BP 431 EP 437 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 332KM UT WOS:000258081900010 PM 18092903 ER PT J AU Mitschke, DB Matsunaga, DS Loebl, K Tatafu, E Robinett, H AF Mitschke, Diane B. Matsunaga, Doris Segal Loebl, Karen Tatafu, Elitei, Jr. Robinett, Hali TI Multi-ethnic adolescents' attitudes toward smoking: A focus group analysis SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article DE adolescent; drama; focus groups; prevention research; primary prevention; tobacco ID TOBACCO AB Purpose. To explore young, multi-ethnic adolescents' attitudes and influences related to cigarette smoking for the purpose of developing and producing a youth-led., tobacco-prevention drama. Design. Focus groups and demographic surveys. Setting. Island of Oahu, Hawaii. Participants. Fifty-four multi-ethnic youth, ranging in age from 10 to 14 years, participated. The study was promoted in schools with a large representation of Hawaiian, Filipino, and Pacific Islander students. Methods. Each of five focus groups was audio-recorded, and an observer recorded extensive notes throughout the sessions. Content analysis consisted of coding focus group notes for recurrent themes and using the audio recording as confirmation. Results. just more than one quarter (n = 15) of the youth had tried smoking, and two-thirds (n 35) currently lived with someone who smoked. Participants expressed the feeling of being surrounded by smoking influences at home, in their communities, and at school. Youth were negatively affected by family members' tobacco use, and they desired skills that could. enable them to help family members stop using tobacco. Conclusion. Family influences may play an important role in youth attitudes toward tobacco use, especially given the cultural significance of extended family and of filial piety that are reflected in many traditional, Asian and Pacific Islander,families. Interventions targeting youth in Asian and Pacific Islander communities should incorporate key cultural references to the extended family and to a respect for elders to establish relevance in the life experiences of young people in these population groups. C1 [Mitschke, Diane B.; Robinett, Hali] Univ Hawaii, Canc Res Ctr Hawaii, Natl Canc Inst, Canc Informat Serv Pacif Reg, Honolulu, HI 96813 USA. [Matsunaga, Doris Segal; Loebl, Karen; Tatafu, Elitei, Jr.] Kalihi Palama Hlth Ctr, Honolulu, HI USA. RP Mitschke, DB (reprint author), Univ Texas Arlington, Sch Social Work, 211 S Cooper St,Box 19129, Arlington, TX 76019 USA. EM dianemitschke@uta.edu NR 17 TC 5 Z9 5 U1 0 U2 4 PU AMER J HEALTH PROMOTION INC PI KEEGO HARBOR PA 1660 CASS LAKE RD, STE 104, KEEGO HARBOR, MI 48320 USA SN 0890-1171 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD JUL-AUG PY 2008 VL 22 IS 6 BP 393 EP 399 DI 10.4278/ajhp.22.6.393 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 323KZ UT WOS:000257446300005 PM 18677879 ER PT J AU Sliwinska-Kowalska, M Noben-Trauth, K Pawelczyk, M Kowalski, TJ AF Sliwinska-Kowalska, Mariola Noben-Trauth, Konrad Pawelczyk, Malgorzata Kowalski, Tomasz Jarema TI Single nucleotide polymorphisms in the Cadherin 23 (CDH23) gene in Polish workers exposed to industrial noise SO AMERICAN JOURNAL OF HUMAN BIOLOGY LA English DT Article ID INDUCED HEARING-LOSS; INCREASES SUSCEPTIBILITY; MICE; MUTATION AB Single nucleotide polymorphisms (SNPs) are the most frequent type of variation in the human genome and may underlie differential susceptibility to common genetic diseases. A candidate gene for susceptibility to noise-induced hearing loss (NIHL) is Cadherin 23 (CDH23). This study aimed to analyze genetic variation in the CDH23 gene in a group of 10 individuals derived from a cohort of 949 workers exposed to noise, and consisted of five persons from each of the resistant and susceptible extremes. DNA samples were collected and the coding exons of CDH23 were sequenced. We identified a total of 35 SNPs: 11 amino acid substitutions, 8 silent nucleotide changes, and 16 substitutions in intervening sequences. Ten of the 11 amino acid substitutions were previously shown also to segregate in a Cuban population. The nonsynonymous SNPs localized to the part of the gene encoding the extracellular domain of Cadherin 23, in particular ectodomains 5, 13, 14, 15, 16, 17, 19, and 22. One amino acid change occurred at a conserved position in ectodomain 5. Our results provide a framework for future study of polymorphisms in CDH23 as risk factor for NIHL. C1 [Sliwinska-Kowalska, Mariola; Pawelczyk, Malgorzata; Kowalski, Tomasz Jarema] Nofer Inst Occupat Med, Dept Audiol & Phoniatr, PL-91348 Lodz, Poland. [Sliwinska-Kowalska, Mariola] Natl Inst Deafness & Other Commun Disorders, Neurogenet Sect, Mol Biol Lab, NIH, Rockville, MD 20850 USA. [Noben-Trauth, Konrad] Med Univ Lodz, Dept Environm Otolaryngol, PL-90549 Lodz, Poland. RP Sliwinska-Kowalska, M (reprint author), Nofer Inst Occupat Med, Dept Audiol & Phoniatr, 8 Sw Teresy St, PL-91348 Lodz, Poland. EM marsliw@imp.lodz.pl RI Sliwinska-Kowalska, Mariola/F-6119-2010; Pawelczyk, Malgorzata/C-9853-2011; Pawelczyk, Malgorzata/F-5447-2013; Pawelczyk, Malgorzata/S-9231-2016 OI Sliwinska-Kowalska, Mariola/0000-0001-7569-3882; FU Intramural NIH HHS NR 15 TC 15 Z9 19 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1042-0533 EI 1520-6300 J9 AM J HUM BIOL JI Am. J. Hum. Biol. PD JUL-AUG PY 2008 VL 20 IS 4 BP 481 EP 483 DI 10.1002/ajhb.20744 PG 3 WC Anthropology; Biology SC Anthropology; Life Sciences & Biomedicine - Other Topics GA 318NV UT WOS:000257099700015 PM 18348277 ER PT J AU Roessler, E Ouspenskaia, MV Karkera, JD Velez, JI Kantipong, A Lacbawan, F Bowers, P Belmont, JW Towbin, JA Goldmuntz, E Feldman, B Muenke, M AF Roessler, Erich Ouspenskaia, Maia V. Karkera, Jayaprakash D. Velez, Jorge I. Kantipong, Amy Lacbawan, Felicitas Bowers, Peter Belmont, John W. Towbin, Jeffrey A. Goldmuntz, Elizabeth Feldman, Benjamin Muenke, Maximilian TI Reduced NODAL signaling strength via mutation of several pathway members including FOXH1 is linked to human heart defects and holoprosencephaly SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID SMAD INTERACTION MOTIF; OF-FUNCTION MUTATIONS; LATERALITY DEFECTS; DIGEORGE-SYNDROME; NKX2.5 MUTATIONS; DISEASE; MICE; ZIC3; ASYMMETRY; GENETICS AB Abnormalities of embryonic patterning are hypothesized to underlie many common congenital malformations in humans including congenital heart defects (CHDs), left-right disturbances (L-R) or laterality, and holoprosencephaly (HPE). Studies in model organisms suggest that Nodal-like factors provide instructions for key aspects of body axis and germ layer patterning; however, the complex genetics of pathogenic gene variant(s) in humans are poorly understood. Here we report our studies of FOXH1, CFC1, and SMAD2 and summarize our mutational analysis of three additional components in the human NODAL-signaling pathway: NODAL, GDF1, and TDGF1. We identify functionally abnormal gene products throughout the pathway that are clearly associated with CHD, laterality, and HPE. Abnormal gene products are most commonly detected in patients within a narrow spectrum of isolated conotruncal heart defects (minimum 5%-10% of subjects), and far less commonly in isolated laterality or HPE patients (similar to 1% for each). The difference in the mutation incidence between these groups is highly significant. We show that apparent gene dosage discrepancies between humans and model organisms can be reconciled by considering a broader combination of sequence variants. Our studies confirm that (1) the genetic vulnerabilities inferred from model organisms with defects in Nodal signaling are indeed analogous to humans; (2) the molecular analysis of an entire signaling pathway is more complete and robust than that of individual genes and presages future studies by whole-genome analysis; and (3) a functional genomics approach is essential to fully appreciate the complex genetic interactions necessary to produce these effects in humans. C1 [Roessler, Erich; Ouspenskaia, Maia V.; Karkera, Jayaprakash D.; Velez, Jorge I.; Kantipong, Amy; Lacbawan, Felicitas; Feldman, Benjamin; Muenke, Maximilian] NHGRI, NIH, Med Genet Branch, Bethesda, MD 20892 USA. [Bowers, Peter] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. [Belmont, John W.; Towbin, Jeffrey A.] Baylor Coll Med, Dept Pediat, Div Cardiol, Houston, TX 77030 USA. [Goldmuntz, Elizabeth] Childrens Hosp Philadelphia, Div Cardiol, Philadelphia, PA 19104 USA. RP Muenke, M (reprint author), NHGRI, NIH, Med Genet Branch, Bethesda, MD 20892 USA. EM mmuenke@nhgri.nih.gov OI Belmont, John/0000-0001-7409-3578; Feldman, Benjamin/0000-0003-4838-8641 FU Intramural NIH HHS; NHLBI NIH HHS [P50 HL74731, R01 HL091771-01, P50 HL074731, R01 HL091771-02, R01 HL091771] NR 38 TC 79 Z9 79 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUL PY 2008 VL 83 IS 1 BP 18 EP 29 DI 10.1016/j.ajhg.2008.05.012 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 328FO UT WOS:000257784000004 PM 18538293 ER PT J AU Foster, MC Hwang, SJ Larson, MG Lichtman, JH Parikh, NI Vasan, RS Levy, D Fox, CS AF Foster, Meredith C. Hwang, Shih-Jen Larson, Martin G. Lichtman, Judith H. Parikh, Nisha I. Vasan, Ramachandran S. Levy, Daniel Fox, Caroline S. TI Overweight, obesity, and the development of stage 3 CKD: The Framingham Heart Study SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE chronic kidney disease; chronic kidney disease risk factors; Framingham Heart Study; obesity; epidemiology; cardiovascular disease risk factors ID GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; BODY-MASS INDEX; COMMUNITY-BASED POPULATION; SERUM CREATININE; RENAL-DISEASE; RISK-FACTORS; CARDIOVASCULAR-DISEASE; GENERAL-POPULATION; METABOLIC SYNDROME AB Background: Prior research yielded conflicting results about the magnitude of the association between body mass index (BMI) and chronic kidney disease (CKD). Study Design: Prospective cohort study. Settings & Participants: Framingham Offspring participants (n = 2,676; 52% women; mean age, 43 years) free of stage 3 CKD at baseline who participated in examination cycles 2 (1978-1981) and 7 (1998-2001). Predictor: BMI. Outcome: Stage 3 CKD (estimated glomerular filtration rate < 59 mL/min/1.73 m(2) for women and < 64 mL/min/1.73 m(2) for men). Measurements: Age-, sex-, and multivariable-adjusted (diabetes, systolic blood pressure, hypertension treatment, current smoking status, and high-density lipoprotein cholesterol level) logistic regression models were used to examine the relationship between BMI at baseline and incident stage 3 CKD and incident dipstick proteinuria (trace or greater). Results: At baseline, 36% of the sample was overweight and 12% was obese; 7.9% (n = 212) developed stage 3 CKD during 18.5 years of follow-up. Relative to participants with normal BMI, there was no association between overweight individuals and stage 3 CKD incidence in age- and sex-adjusted models (odds ratio [OR], 1.29; 95% confidence interval [CI], 0.93 to 1.81; P = 0.1) or multivariable models (OR, 1.06; 95% CI, 0.75 to 1.50; P = 0.8). Obese individuals had a 68% increased odds of developing stage 3 CKD (OR, 1.68; 95% CI, 1.10 to 2.57; P = 0.02), which became nonsignificant in multivariable models (OR, 1.09; 95% CI, 0.69 to 1.73; P = 0.7). Similar findings were observed when BMI was modeled as a continuous variable or quartiles. Incident proteinuria occurred in 14.4%; overweight and obese individuals were at increased odds of proteinuria in multivariable models (OR, 1.43; 95% CI, 1.09 to 1.88; OR, 1.56; 95% CI, 1.08 to 2.26, respectively). Limitations: BMI is measure of generalized obesity and not abdominal obesity. Participants are predominantly white, and these findings may not apply to different ethnic groups. Conclusions: Obesity is associated with increased risk of developing stage 3 CKD, which was no longer significant after adjustment for known cardiovascular disease risk factors. The relationship between obesity and stage 3 CKD may be mediated through cardiovascular disease risk factors. C1 [Foster, Meredith C.; Hwang, Shih-Jen; Levy, Daniel; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Foster, Meredith C.; Hwang, Shih-Jen; Levy, Daniel; Fox, Caroline S.] NHLBI, NIH, Bethesda, MD 20892 USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Lichtman, Judith H.] Yale Univ, Sch Publ Hlth, Div Chron Dis Epidemiol, New Haven, CT USA. [Parikh, Nisha I.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Ste 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [N01 HC025195, N01-HC-25195, N01HC25195] NR 35 TC 126 Z9 134 U1 2 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JUL PY 2008 VL 52 IS 1 BP 39 EP 48 DI 10.1053/j.ajkd.2008.03.003 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 329QV UT WOS:000257886600007 PM 18440684 ER PT J AU Martin, MR Lindquist, T Kotchen, TA AF Martin, Michael R. Lindquist, Teresa Kotchen, Theodore A. TI Why are peer review outcomes less favorable for clinical science than for basic science grant applications? SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID INSTITUTES-OF-HEALTH; NIH; INVESTIGATORS; PERSPECTIVE; CHALLENGES C1 [Kotchen, Theodore A.] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. [Martin, Michael R.; Lindquist, Teresa] NIH, Ctr Sci Review, Bethesda, MD 20892 USA. RP Kotchen, TA (reprint author), Med Coll Wisconsin, Dept Med, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM tkotchen@mcw.edu FU Intramural NIH HHS [Z99 RG999999] NR 18 TC 1 Z9 1 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUL PY 2008 VL 121 IS 7 BP 637 EP 641 DI 10.1016/j.amjmed.2008.03.031 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 318QM UT WOS:000257106700019 PM 18589061 ER PT J AU Grobman, WA Lai, YL Landon, MB Spong, CY Leveno, KJ Rouse, DJ Varner, MW Moawad, AH Caritis, SN Harper, M Wapner, RJ Sorokin, Y Miodovnik, M Carpenter, M O'Sullivan, MJ Sibai, BM Langer, O Thorp, JM Ramin, SM Mercer, BM AF Grobman, William A. Lai, Yinglei Landon, Mark B. Spong, Catherine Y. Leveno, Kenneth J. Rouse, Dwight J. Varner, Michael W. Moawad, Atef H. Caritis, Steve N. Harper, Margaret Wapner, Ronald J. Sorokin, Yoram Miodovnik, Menachem Carpenter, Marshall O'Sullivan, Mary J. Sibai, Baha M. Langer, Oded Thorp, John M. Ramin, Susan M. Mercer, Brian M. CA Natl Inst Child Hlth Human Dev Maternal-Fetal Med Units TI Prediction of uterine rupture associated with attempted vaginal birth after cesarean delivery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE prediction; uterine rupture; vaginal birth after cesarean delivery ID TRIAL; LABOR; RISK AB OBJECTIVE: The purpose of this study was to develop a model that predicts individual-specific risk of uterine rupture during an attempted vaginal birth after cesarean delivery. STUDY DESIGN: Women with 1 previous low-transverse cesarean delivery who underwent a trial of labor with a term singleton were identified in a concurrently collected database of deliveries that occurred at 19 academic centers during a 4-year period. We analyzed different classification techniques in an effort to develop an accurate prediction model for uterine rupture. RESULTS: Of the 11,855 women who were available for analysis, 83 women (0.7%) had had a uterine rupture. The optimal final prediction model, which was based on a logistic regression, included 2 variables: any previous vaginal delivery (odds ratio, 0.44; 95% CI, 0.27-0.71) and induction of labor (odds ratio, 1.73; 95% CI, 1.11-2.69). This model, with a c-statistic of 0.627, had poor discriminating ability and did not allow the determination of a clinically useful estimate of the probability of uterine rupture for an individual patient. CONCLUSION: Factors that were available before or at admission for delivery cannot be used to predict accurately the relatively small proportion of women at term who will experience a uterine rupture during an attempted vaginal birth after cesarean delivery. C1 [Grobman, William A.] Northwestern Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA. [Lai, Yinglei] George Washington Univ, Ctr Biostat, Washington, DC USA. [Landon, Mark B.] Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. [Spong, Catherine Y.] Natl Inst Child Hlth & Human Dev, Bethesda, MD USA. [Leveno, Kenneth J.] Univ Texas SW Med Ctr Dallas, Dept Obstet, Dallas, TX 75390 USA. [Leveno, Kenneth J.] Univ Texas SW Med Ctr Dallas, Dept Gynecol, Dallas, TX 75390 USA. [Rouse, Dwight J.] Univ Alabama, Birmingham, AL USA. [Varner, Michael W.] Univ Chicago, Chicago, IL 60637 USA. [Moawad, Atef H.] Univ Utah, Salt Lake City, UT USA. [Caritis, Steve N.] Univ Pittsburgh, Pittsburgh, PA USA. [Harper, Margaret] Wake Forest Univ, Winston Salem, NC 27109 USA. [Wapner, Ronald J.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Sorokin, Yoram] Wayne State Univ, Detroit, MI USA. [Miodovnik, Menachem] Univ Cincinnati, Cincinnati, OH USA. [Miodovnik, Menachem] Columbia Univ, Cincinnati, OH USA. [Carpenter, Marshall] Brown Univ, Providence, RI 02912 USA. [O'Sullivan, Mary J.] Univ Miami, Miami, FL USA. [Sibai, Baha M.] Univ Tennessee, Memphis, TN USA. [Langer, Oded] Univ Texas San Antonio, San Antonio, TX USA. [Thorp, John M.] Univ N Carolina, Chapel Hill, NC USA. [Ramin, Susan M.] Univ Texas Houston, Houston, TX USA. [Mercer, Brian M.] Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Grobman, WA (reprint author), 333 E Super St,Suite 410, Chicago, IL 60611 USA. EM w-grobman@northwestern.edu RI Varner, Michael/K-9890-2013 OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973 FU NCRR NIH HHS [UL1 RR025741]; NICHD NIH HHS [U10 HD040512-01, HD21410, HD21414, HD27860, HD27861, HD27869, HD27915, HD27917, HD34116, HD34136, HD34208, HD34210, HD36801, HD40485, HD40500, HD40512, HD40544, HD40545, HD40560, U01 HD036801, U10 HD021410, U10 HD027860, U10 HD027869, U10 HD027905, U10 HD027915, U10 HD027917, U10 HD034116, U10 HD034122, U10 HD034136, U10 HD034208, U10 HD036801, U10 HD040485, U10 HD040500, U10 HD040512, U10 HD040512-02, U10 HD040512-02S1, U10 HD040512-03, U10 HD040512-04, U10 HD040512-05, U10 HD040512-06, U10 HD040512-07, U10 HD040512-08, U10 HD040544, U10 HD040545, U10 HD040560, UG1 HD027869, UG1 HD027915, UG1 HD034116, UG1 HD034208, UG1 HD040485, UG1 HD040500, UG1 HD040512, UG1 HD040544, UG1 HD040545, UG1 HD040560] NR 13 TC 8 Z9 10 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUL PY 2008 VL 199 IS 1 AR 30.e1 DI 10.1016/j.ajog.2008.03.039 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 320AD UT WOS:000257205200008 PM 18439555 ER PT J AU Xu, TM Korn, EL Liu, Y Oh, HS Lee, KH Boyd, RL Baumrind, S AF Xu, Tian-Min Korn, Edward L. Liu, Yan Oh, Hee Soo Lee, Ki Heon Boyd, Robert L. Baumrind, Sheldon TI Facial attractiveness: Ranking of end-of-treatment facial photographs by pairs of Chinese and US orthodontists SO AMERICAN JOURNAL OF ORTHODONTICS AND DENTOFACIAL ORTHOPEDICS LA English DT Article ID SOFT-TISSUE PROFILE; CEPHALOMETRIC ANALYSIS; LIP POSITION; PREFERENCES; AESTHETICS; PERCEPTIONS; POPULATION; DIAGNOSIS; ESTHETICS; KEYS AB Introduction: In this study, we assessed agreement and disagreement among pairs of Chinese and US orthodontists in the ranking for "facial attractiveness" of end-of-treatment photographs of growing Chinese and white orthodontic patients. Methods: Two groups of orthodontist-judges participated: from the University of the Pacific, School of Dentistry, in California and from Peking University School and Hospital of Stomatology in China. Each judge independently ranked standard clinical sets of profile, frontal, and frontal-smiling photographs of 43 white patients and 48 Chinese patients. Pearson correlations were generated for a total of 1980 rankings by pairs of judges. Results: The resulting correlations ranged from +0.004 to +0.96 with a median of +0.54. Of these, 18.7% were lower than 0.4; 41.0% were lower than 0.5; 68.8% were lower than 0.6; 91.6% were lower than 0.7; and only 8.4% were greater than 0.7. As had been anticipated, correlations between judges were higher when they ranked patients of their own ethnicity than when they ranked patients of different ethnicity, but the differences were smaller than had been expected. The rankings of no pair of judges correlated negatively. This is to say that no pair of judges, whether of the same or different ethnicity, ranked the patients so that those 1 judge tended to find attractive were consistently found unattractive by the other. Conclusions: The distribution of levels of agreement between pairs of orthodontists did not differ substantially whether the pairs included 2 US orthodontists, 2 Chinese orthodontists, or 1 US and 1 Chinese orthodontist. As might be expected, the pairs of Chinese orthodontists agreed with each other slightly better on average when ranking Chinese patients, and the pairs of US orthodontists agreed with each other slightly better on average when ranking white American patients, but the overall differences were small. These findings appear consistent with the inference that, on average, judgments of "facial attractiveness" by orthodontists at the 2 venues are more similar than had been expected for patients of Chinese and white ethnicity. C1 [Xu, Tian-Min; Liu, Yan] Peking Univ, Sch & Hosp Stomatol, Dept Orthodont, Beijing 100871, Peoples R China. [Korn, Edward L.] NCI, Biometr Res Branch, NIH, Rockville, MD USA. [Oh, Hee Soo; Boyd, Robert L.; Baumrind, Sheldon] Univ Pacific, Sch Dent, Dept Orthodont, San Francisco, CA 94115 USA. [Lee, Ki Heon] Chonnam Natl Univ, Dept Orthodont, Kwangju, South Korea. [Baumrind, Sheldon] Univ Pacific, Sch Dent, Craniofacial Res Instrumentat Lab, San Francisco, CA 94115 USA. RP Baumrind, S (reprint author), Univ Pacific, Craniofacial Res Instrumentat Lab, Arthur A Dugoni Sch Dent, Room 617,2115 Webster St, San Francisco, CA 94115 USA. EM sbaumrind@pacific.edu FU NIDCR NIH HHS [DE07332, DE08713] NR 39 TC 10 Z9 12 U1 1 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0889-5406 J9 AM J ORTHOD DENTOFAC JI Am. J. Orthod. Dentofac. Orthop. PD JUL PY 2008 VL 134 IS 1 BP 74 EP 84 DI 10.1016/j.ajodo.2006.08.023 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 323JB UT WOS:000257441300020 PM 18617106 ER PT J AU Pacher, P Szabot, C AF Pacher, Pal Szabot, Csaba TI Role of the peroxynitrite-poly(ADP-ribose) polymerase pathway in human disease SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Review ID PEROXYNITRITE DECOMPOSITION CATALYST; NITRIC-OXIDE SYNTHASE; SYSTEMIC-LUPUS-ERYTHEMATOSUS; ADP-RIBOSE POLYMERASE; RESPIRATORY-DISTRESS-SYNDROME; BRONCHOALVEOLAR LAVAGE FLUID; ACUTE MYOCARDIAL-INFARCTION; CELLULAR-ENERGY DEPLETION; TRAUMATIC BRAIN-INJURY; OXIDATIVE DNA-DAMAGE AB Throughout the last 2 decades, experimental evidence from in vitro studies and preclinical models of disease has demonstrated that reactive oxygen and nitrogen species, including the reactive oxidant peroxynitrite, are generated in parenchymal, endothelial, and infiltrating inflammatory cells during stroke, myocardial and other forms of reperfusion injury, myocardial hypertrophy and heart failure, cardiomyopathies, circulatory shock, cardiovascular aging, atherosclerosis and vascular remodeling after injury, diabetic complications, and neurodegenerative disorders. Peroxynitrite and other reactive species induce oxidative DNA damage and consequent activation of the nuclear enzyme poly(ADP-ribose) polymerase 1 (PARP-1), the most abundant isoform of the PARP enzyme family. PARP overactivation depletes its substrate NAD(+), slowing the rate of glycolysis, electron transport, and ATP formation, eventually leading to functional impairment or death of cells, as well as up-regulation of various proinflammatory pathways. In related animal models of disease, peroxynitrite neutralization or pharmacological inhibition of PARP provides significant therapeutic benefits. Therefore, novel antioxidants and PARP inhibitors have entered clinical development for the experimental therapy of various cardiovascular and other diseases. This review focuses on the human data available on the pathophysiological relevance of the peroxynitrite-PARP pathway in a wide range of disparate diseases, ranging from myocardial ischemia/reperfusion injury, myocarditis, heart failure, circulatory shock, and diabetic complications to atherosclerosis, arthritis, colitis, and neurodegenerative disorders. C1 [Pacher, Pal] NIAAA, Sect Oxidat Stress & Tissue Injury, Lab Phys Studies, Natl Inst Hlth, Bethesda, MD 20892 USA. [Szabot, Csaba] Univ Med & Dent New Jersey, Sch Med, Dept Surg, Newark, NJ 07103 USA. RP Pacher, P (reprint author), NIAAA, Sect Oxidat Stress & Tissue Injury, Lab Phys Studies, Natl Inst Hlth, 5625 Fishers Lane,MSC-9413, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov; szabocsaba@aol.com RI Pacher, Pal/B-6378-2008 OI Pacher, Pal/0000-0001-7036-8108 FU Intramural NIH HHS [Z01 AA000375-02, Z99 AA999999]; NIGMS NIH HHS [R01 GM060915] NR 130 TC 182 Z9 190 U1 3 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUL PY 2008 VL 173 IS 1 BP 2 EP 13 DI 10.2353/ajpath.2008.080019 PG 12 WC Pathology SC Pathology GA 320VO UT WOS:000257263400001 PM 18535182 ER PT J AU Flanders, KC Ho, BM Arany, PR Stuelten, C Mamura, M Paterniti, MO Sowers, A Mitchell, JB Roberts, AB AF Flanders, Kathleen C. Ho, Benjamin M. Arany, Praveen R. Stuelten, Christina Mamura, Mizuko Paterniti, Miya Okada Sowers, Anastasia Mitchell, James B. Roberts, Anita B. TI Absence of Smad3 induces neutrophil migration after cutaneous irradiation - Possible contribution to subsequent radioprotection SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; HEAT-SHOCK PROTEINS; MICE LACKING SMAD3; TRANSFORMING GROWTH-FACTOR-BETA-1; IONIZING-RADIATION; TGF-BETA; GENE-EXPRESSION; IN-VIVO; INJURY; SKIN AB Our previous work showed that 6 weeks after cutaneous irradiation, mice null (knockout, KO) for Smad3, a cytoplasmic downstream mediator of transforming growth factor-beta, demonstrate less epidermal acanthosis and dermal inflammation than wild-type (WT) Smad3 mice. Analysis of the kinetics of inflammation showed that 6 to 8 hours after skin irradiation, there was a transient sevenfold increase in neutrophil influx in Smad3 KO mice compared with WT. Herein we describe bone marrow transplantation and skin grafting between WT and KO mice to assess the contribution of the neutrophil genotype compared with that of irradiated skin to the induction of neutrophil migration after irradiation. Results from bone marrow transplantation showed that WT marrow transplanted into KO mice enhanced neutrophil migration 6 to 8 hours after irradiation by 3.2-fold compared with KO marrow in WT mice. KO skin grafted onto either WT or KO animals showed a sixfold elevation of neutrophils after irradiation compared with grafted WT skin. These results suggest that the genotype of the irradiated skin, rather than the inflammatory cell, controls neutrophil influx. Circulating neutrophils, increased in. WT mice after injection of granulocyte colony-stimulating factor, resulted in increased neutrophil migration to the skin 6 to 8 hours after irradiation and less skin damage 6 weeks after irradiation compared with untreated WT mice. Thus, early responses, including enhanced neutrophil influx, appear to contribute to subsequent cutaneous radioprotection. C1 [Flanders, Kathleen C.; Ho, Benjamin M.; Arany, Praveen R.; Stuelten, Christina; Mamura, Mizuko; Paterniti, Miya Okada; Roberts, Anita B.] NCI, Natl Inst Hlth, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. [Sowers, Anastasia; Mitchell, James B.] NCI, Natl Inst Hlth, Radiat Biol Branch, Bethesda, MD 20892 USA. RP Flanders, KC (reprint author), NCI, Lab Canc Biol & Genet, Bldg 37-Rm 5046B,37 Convent Dr, Bethesda, MD 20892 USA. EM flanderk@dce41.nci.nih.gov OI Mamura, Mizuko/0000-0003-4531-0144 NR 38 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUL PY 2008 VL 173 IS 1 BP 68 EP 76 DI 10.2353/ajpath.2008.070937 PG 9 WC Pathology SC Pathology GA 320VO UT WOS:000257263400007 PM 18502822 ER PT J AU McEntee, MF Ziegler, C Reel, D Tomer, K Shoieb, A Ray, M Li, X Neilsen, N Lih, FB O'Rourke, D Whelan, J AF McEntee, Michael F. Ziegler, Carol Reel, Danielle Tomer, Kenneth Shoieb, Ahmed Ray, Mark Li, Xiaoou Neilsen, Nancy Lih, Fred B. O'Rourke, Dorcas Whelan, Jay TI Dietary n-3 polyunsaturated fatty acids enhance hormone ablation therapy in androgen-dependent prostate cancer SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ALPHA-LINOLENIC ACID; DEPRIVATION THERAPY; ARACHIDONIC-ACID; 15-LIPOXYGENASE-2 15-LOX2; EICOSANOID PRODUCTION; PROSTAGLANDIN E-2; NUDE-MICE; IN-VIVO; XENOGRAFT; RISK AB Hormone ablation therapy typically causes regression of prostate cancer and represents an important means of treating this disease, particularly after metastasis. However, hormone therapy inevitably loses its effectiveness as tumors become androgen-independent, and this conversion often leads to death because of subsequent poor responses to other forms of treatment. Because environmental factors, such as diet, have been strongly linked to prostate cancer, we examined the affects of dietary polyunsaturated fatty acids (PUFAs; at 1.5 wt%) on growth of androgen-dependent (CWR22) and androgen-independent (CWR22R) human prostatic cancer xenografts, the acute response of CWR22 tumors to ablation therapy, and their progression to androgen independence. Significant diet-induced changes in tumor n-3 or n-6 PUFA content had no affect on CWR22 or CWR22R tumors growing with or without androgen support, respectively. However, dietary changes that increased tumor eicosapentaenoic acid and linoleic acid content enhanced responses to ablation therapy, measured by cancer cell apoptosis and mitosis. In addition, relapse to androgen-independent growth (measured by renewed increases in tumor volume and serum prostate-specific antigen after ablation) positively correlated with tumor arachidonic acid content. There was no correlation between expression of 15-lipoxygenase isozymes or their products and tumor growth or responses to ablation. In conclusion, dietary n-3 PUFA may enhance the response of prostate cancer to ablation therapy and retard progression to androgen-independent growth by altering tumor PUFA content. C1 [McEntee, Michael F.; Ziegler, Carol; Reel, Danielle; Shoieb, Ahmed; Ray, Mark; Li, Xiaoou; Neilsen, Nancy] Univ Tennessee, Dept Pathobiol, Knoxville, TN 37996 USA. [O'Rourke, Dorcas] Univ Tennessee, Dept Comparat Med, Knoxville, TN 37996 USA. [Whelan, Jay] Univ Tennessee, Dept Nutr, Knoxville, TN 37996 USA. [Tomer, Kenneth; Lih, Fred B.] Natl Inst Environm Hlth Sci, Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. RP McEntee, MF (reprint author), Univ Tennessee, Dept Pathobiol, 2407 River Dr,Rm A201, Knoxville, TN 37996 USA. EM mmcentee@utk.edu RI Tomer, Kenneth/E-8018-2013; OI McEntee, Michael/0000-0002-1616-3715 FU Intramural NIH HHS NR 53 TC 34 Z9 35 U1 0 U2 4 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUL PY 2008 VL 173 IS 1 BP 229 EP 241 DI 10.2353/ajpath.2008.070989 PG 13 WC Pathology SC Pathology GA 320VO UT WOS:000257263400021 PM 18556778 ER PT J AU Cogger, VC Arias, IM Warren, A McMahon, AC Kiss, DL Avery, VM Le Couteur, DG AF Cogger, Victoria C. Arias, Irwin M. Warren, Alessandra McMahon, Aisling C. Kiss, Debra L. Avery, Vicky M. Le Couteur, David G. TI The response of fenestrations, actin, and caveolin-1 to vascular endothelial growth factor in SK Hep1 cells SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE sinusoidal endothelial cell; fenestration; liver ID GLYCATION END-PRODUCTS; RAT-LIVER; SINUSOIDAL ENDOTHELIUM; CYTOCHALASIN-B; KUPFFER CELLS; IN-VITRO; PERMEABILITY; EXPRESSION; ENDOCYTOSIS; LIPOPROTEIN AB To study the regulation of fenestrations by vascular endothelial growth factor in liver sinusoidal endothelial cells, SK Hep1 cells were transfected with green fluorescence protein (GFP)-actin and GFP-caveolin-1. SK Hep1 cells had pores; some of which appeared to be fenestrations ( diameter 55 +/- 28 nm, porosity 2.0 +/- 1.4%), rudimentary sieve plates, bristlecoated micropinocytotic vesicles and expressed caveolin-1, von Willebrand factor, vascular endothelial growth factor receptor-2, endothelial nitric oxide synthase and clathrin, but not CD31. There was avid uptake of formaldehyde serum albumin, consistent with endocytosis. Vascular endothelial growth factor caused an increase in porosity to 4.8 +/- 2.6% ( P < 0.01) and pore diameter to 104 +/- 59 nm ( P < 0.001). GFP-actin was expressed throughout the cells, whereas GFP-caveolin1 had a punctate appearance; both responded to vascular endothelial growth factor by contraction toward the nucleus over hours in parallel with the formation of fenestrations. SK Hep1 cells resemble liver sinusoidal endothelial cells, and the vascular endothelial growth factor-induced formation of fenestration-like pores is preceded by contraction of actin cytoskeleton and attached caveolin-1 toward the nucleus. C1 [Cogger, Victoria C.; Warren, Alessandra; McMahon, Aisling C.; Le Couteur, David G.] Concord RG Hosp, Ctr Educ & Res Aging, Concord, NSW 2139, Australia. [Cogger, Victoria C.; Warren, Alessandra; McMahon, Aisling C.; Le Couteur, David G.] Concord RG Hosp, ANZAC Res Inst, Concord, NSW 2139, Australia. [Cogger, Victoria C.; Warren, Alessandra; McMahon, Aisling C.; Le Couteur, David G.] Univ Sydney, Sydney, NSW 2006, Australia. [Cogger, Victoria C.; Arias, Irwin M.] NIH, Bethesda, MD 20892 USA. [Cogger, Victoria C.; Arias, Irwin M.] NICHHD, Bethesda, MD 20892 USA. [Kiss, Debra L.; Avery, Vicky M.] Griffith Univ, Eskitis Inst Cell & Mol Therapies, Brisbane, Qld 4111, Australia. RP Le Couteur, DG (reprint author), Concord RG Hosp, Ctr Educ & Res Aging, Hosp Rd, Concord, NSW 2139, Australia. EM dlecouteur@med.usyd.edu.au RI Avery, Vicky/A-5449-2010 NR 59 TC 19 Z9 20 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JUL 1 PY 2008 VL 295 IS 1 BP G137 EP G145 DI 10.1152/ajpgi.00069.2008 PG 9 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 325ML UT WOS:000257592900014 PM 18497335 ER PT J AU Chantler, PD Melenovsky, V Schulman, SP Gerstenblith, G Becker, LC Ferrucci, L Fleg, JL Lakatta, EG Najjar, SS AF Chantler, Paul D. Melenovsky, Vojtech Schulman, Steven P. Gerstenblith, Gary Becker, Lewis C. Ferrucci, Luigi Fleg, Jerome L. Lakatta, Edward G. Najjar, Samer S. TI The sex-specific impact of systolic hypertension and systolic blood pressure on arterial-ventricular coupling at rest and during exercise SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE arterial elastance; left ventricular end-systolic elastance; systolic hypertension; exercise; sex ID PRESERVED EJECTION FRACTION; HEART-FAILURE; CARDIAC-FUNCTION; WAVE REFLECTION; FAILING HEART; VASCULAR LOAD; HEALTHY-MEN; AGE; ELASTANCE; GENDER AB In healthy subjects the arterial system and the left ventricle (LV) are tightly coupled at rest to optimize cardiac performance. Systolic hypertension (SH) is a major risk factor for heart failure and is associated with structural and functional alterations in the arteries and the LV. The effects of SH and resting systolic blood pressure (SBP) on arterial-ventricular coupling (EaI/ELVI) at rest, at peak exercise, and during recovery are not well described. We noninvasively characterized EaI/ELVI as end-systolic volume index/stroke volume index in subjects who were normotensive (NT, n = 203) or had SH (brachial SBP >= 140 mmHg, n = 79). Cardiac volumes were measured at rest and throughout exhaustive upright cycle exercise with gated blood pool scans. EaI/ELVI reserve was calculated by subtracting peak from resting EaI/ELVI. At rest, EaI/ELVI did not differ between SH and NT men but was 23% (P = 0.001) lower in SH vs. NT women. EaI/ELVI did not differ between SH and NT men or women at peak exercise or during recovery. Nevertheless, EaI/ELVI reserve was 61% (P = 0.001) lower in SH vs. NT women. Similarly, resting SBP (as a continuous variable) was not associated with EaI/ELVI in men (beta = -0.12, P = 0.17) but was inversely associated with EaI/ELVI in women (beta = -0.47, P < 0.001). SH and a higher resting brachial SBP are associated with a lower EaI/ELVI at rest in women but not in men, and SH women have an attenuated EaI/ELVI reserve. Whether a smaller EaI/ELVI reserve leads to functional limitations warrants further examination. C1 [Chantler, Paul D.; Lakatta, Edward G.; Najjar, Samer S.] NIA, Cardiovasc Sci Lab, NIH, Harbor Hosp, Baltimore, MD 21225 USA. [Melenovsky, Vojtech] Inst Clin & Expt Med, Dept Cardiol, Prague, Czech Republic. [Schulman, Steven P.; Gerstenblith, Gary; Becker, Lewis C.] Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, NIH, Clin Res Branch, Baltimore, MD 21225 USA. [Fleg, Jerome L.] NHLBI, Div Cardiovasc Dis, Bethesda, MD 20892 USA. RP Najjar, SS (reprint author), NIA, Cardiovasc Sci Lab, NIH, Harbor Hosp, 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA. EM najjarsa@mail.nih.gov OI Melenovsky, Vojtech/0000-0001-8921-7078 FU Intramural NIH HHS NR 45 TC 23 Z9 25 U1 2 U2 12 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JUL PY 2008 VL 295 IS 1 BP H145 EP H153 DI 10.1152/ajpheart.01179.2007 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 325MU UT WOS:000257593800019 PM 18456731 ER PT J AU Howden, R Liu, E Miller-DeGraff, L Keener, HL Walker, C Clark, JA Myers, PH Rouse, DC Wiltshire, T Kleeberger, SR AF Howden, Reuben Liu, Eric Miller-DeGraff, Laura Keener, Heather L. Walker, Christopher Clark, James A. Myers, Page H. Rouse, D. Clay Wiltshire, Tim Kleeberger, Steven R. TI The genetic contribution to heart rate and heart rate variability in quiescent mice SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE electrocardiography; autonomic nervous system; ventilation ID SYMPATHOVAGAL BALANCE; MYOCARDIAL-INFARCTION; INBRED STRAINS; RISK; PRESSURE; DYNAMICS; INTERVAL; PATTERN; TRAITS; FAMILY AB Recent studies have suggested a genetic component to heart rate (HR) and HR variability (HRV). However, a systematic examination of the genetic contribution to the variation in HR and HRV has not been performed. This study investigated the genetic contribution to HR and HRV using a wide range of inbred and recombinant inbred (RI) mouse strains. Electrocardiogram data were recorded from 30 strains of inbred mice and 29 RI strains. Significant differences in mean HR and total power (TP) HRV were identified between inbred strains and RI strains. Multiple significant differences within the strain sets in mean low-frequency (LF) and high-frequency (HF) power were also found. No statistically significant concordance was found between strain distribution patterns for HR and HRV phenotypes. Genomewide interval mapping identified a significant quantitative trait locus (QTL) for HR [LOD (likelihood of the odds) score = 3.763] on chromosome 6 [peak at 53.69 megabases (Mb); designated HR 1 (Hr1)]. Suggestive QTLs for TP were found on chromosomes 2, 4, 5, 6, and 14. A suggestive QTL for LF was found on chromosome 16; for HF, we found one significant QTL on chromosome 5 (LOD score = 3.107) [peak at 53.56 Mb; designated HRV-high-frequency 1 (Hrvhf1)] and three suggestive QTLs on chromosomes 2, 11 and 15. In conclusion, the results demonstrate a strong genetic component in the regulation of resting HR and HRV evidenced by the significant differences between strains. A lack of correlation between HR and HRV phenotypes in some inbred strains suggests that different sets of genes control the phenotypes. Furthermore, QTLs were found that will provide important insight to the genetic regulation of HR and HRV at rest. C1 [Howden, Reuben; Liu, Eric; Miller-DeGraff, Laura; Keener, Heather L.; Walker, Christopher; Clark, James A.; Myers, Page H.; Rouse, D. Clay; Kleeberger, Steven R.] NIEHS, Biol Res Labs, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. [Wiltshire, Tim] Gen Inst Novartis Res Fdn, San Diego, CA USA. RP Howden, R (reprint author), NIEHS, Biol Res Labs, Dept Hlth & Human Serv, NIH, 111 TW Alexander Dr Bldg 101,Rm E-214,Res Triangl, Res Triangle Pk, NC 27709 USA. EM howden@niehs.nih.gov FU Intramural NIH HHS NR 42 TC 15 Z9 15 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JUL PY 2008 VL 295 IS 1 BP H59 EP H68 DI 10.1152/ajpheart.00941.2007 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 325MU UT WOS:000257593800009 PM 18456734 ER PT J AU Krajewski, ML Hsu, LL Gladwin, MT AF Krajewski, Megan L. Hsu, Lewis L. Gladwin, Mark T. TI The proverbial chicken or the egg? Dissection of the role of cell-free hemoglobin versus reactive oxygen species in sickle cell pathophysiology SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Editorial Material ID NITRIC-OXIDE BIOAVAILABILITY; GARDOS CHANNEL ACTIVITY; PULMONARY-HYPERTENSION; ENDOTHELIAL DYSFUNCTION; HEME OXYGENASE-1; TRANSGENIC MICE; DISEASE; HEMOLYSIS; ARGININE; NITRATION C1 [Krajewski, Megan L.; Gladwin, Mark T.] NHLBI, Pulm & Vasc Med Branch, Dept Crit Care Med, Ctr Clin,NIH, Bethesda, MD 20892 USA. [Hsu, Lewis L.] St Christophers Hosp Children, Marian Anderson Comprehens Sickle Cell Ctr, Philadelphia, PA 19133 USA. RP Gladwin, MT (reprint author), NHLBI, Pulm & Vasc Med Branch, Dept Crit Care Med, Ctr Clin,NIH, Bldg 10-CRC,Rm 5-5140,10 Ctr Dr MSC 1454, Bethesda, MD 20892 USA. EM mgladwin@nih.gov NR 35 TC 13 Z9 14 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 EI 1522-1539 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JUL PY 2008 VL 295 IS 1 BP H4 EP H7 DI 10.1152/ajpheart.00499.2008 PG 4 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 325MU UT WOS:000257593800002 PM 18502905 ER PT J AU Gerszten, RE Accurso, F Bernard, GR Caprioli, RM Klee, EW Klee, GG Kullo, I Laguna, TA Roth, FP Sabatine, M Srinivas, P Wang, TJ Ware, LB AF Gerszten, Robert E. Accurso, Frank Bernard, Gordon R. Caprioli, Richard M. Klee, Eric W. Klee, George G. Kullo, Iftikhar Laguna, Theresa A. Roth, Frederick P. Sabatine, Marc Srinivas, Pothur Wang, Thomas J. Ware, Lorraine B. CA NHLBI Clinical Proteomics Programs TI Challenges in translating plasma proteomics from bench to bedside: update from the NHLBI Clinical Proteomics Programs SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE protein content; proteome ID LOW ABUNDANCE PROTEINS; MASS-SPECTROMETRY; HUMAN SERUM; MICROARRAY TECHNOLOGY; RISK-FACTORS; PREDICTION; BIOMARKERS; ANTIBODIES; MULTIPLEX; DEPLETION AB The emerging scientific field of proteomics encompasses the identification, characterization, and quantification of the protein content or proteome of whole cells, tissues, or body fluids. The potential for proteomic technologies to identify and quantify novel proteins in the plasma that can function as biomarkers of the presence or severity of clinical disease states holds great promise for clinical use. However, there are many challenges in translating plasma proteomics from bench to bedside, and relatively few plasma biomarkers have successfully transitioned from proteomic discovery to routine clinical use. Key barriers to this translation include the need for "orthogonal" biomarkers (i.e., uncorrelated with existing markers), the complexity of the proteome in biological samples, the presence of high abundance proteins such as albumin in biological samples that hinder detection of low abundance proteins, false positive associations that occur with analysis of high dimensional datasets, and the limited understanding of the effects of growth, development, and age on the normal plasma proteome. Strategies to overcome these challenges are discussed. C1 [Gerszten, Robert E.; Wang, Thomas J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Gerszten, Robert E.; Wang, Thomas J.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Accurso, Frank; Laguna, Theresa A.] Univ Colorado Denver & Hlth Sci, Dept Pediat, Denver, CO USA. [Bernard, Gordon R.; Ware, Lorraine B.] Vanderbilt Univ, Dept Med, Div Allergy Pulm & Crit Care Med, Nashville, TN USA. [Caprioli, Richard M.] Vanderbilt Univ, Med Ctr, Mass Spectrometry Res Ctr, Nashville, TN USA. [Klee, Eric W.; Klee, George G.] Mayo Clin & Mayo Fdn, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Kullo, Iftikhar] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA. [Sabatine, Marc] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc, Boston, MA USA. [Sabatine, Marc] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Srinivas, Pothur] NHLBI, NIH, Bethesda, MD 20892 USA. RP Ware, LB (reprint author), T1218 MCN,1161 21st Ave S, Nashville, TN 37232 USA. EM lorraine.ware@vanderbilt.edu RI Roth, Frederick/H-6308-2011; OI Roth, Frederick/0000-0002-6628-649X FU NHLBI NIH HHS [U01 HL081332] NR 51 TC 46 Z9 46 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD JUL PY 2008 VL 295 IS 1 BP L16 EP L22 DI 10.1152/ajplung.00044.2008 PG 7 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 321VZ UT WOS:000257335900002 PM 18456800 ER PT J AU Lui, JC Finkielstain, GP Barnes, KM Baron, J AF Lui, Julian C. Finkielstain, Gabriela P. Barnes, Kevin M. Baron, Jeffrey TI An imprinted gene network that controls mammalian somatic growth is down-regulated during postnatal growth deceleration in multiple organs SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE imprinting; growth regulation; methylation; Zac1 ID BECKWITH-WIEDEMANN-SYNDROME; CDK INHIBITOR; EMBRYONIC GROWTH; MICE LACKING; P57(KIP2); MOUSE; METHYLATION; DISRUPTION; RAT; DIFFERENTIATION AB In mammals, somatic growth is rapid in early postnatal life but decelerates with age and eventually halts, thus determining the adult body size of the species. This growth deceleration, which reflects declining proliferation, occurs simultaneously in multiple organs yet appears not to be coordinated by a systemic mechanism. We, therefore, hypothesized that growth deceleration results from a growth-limiting genetic program that is common to multiple tissues. Here, we identified a set of 11 imprinted genes that show down-regulation of mRNA expression with age in multiple organs. For these genes, Igf2, H19, Plagl1, Mest, Peg3, Dlk1, Gtl2, Grb10, Ndn, Cdkn1c, and SLC38a4, the declines show a temporal pattern similar to the decline in growth rate. All 11 genes have been implicated in the control of cell proliferation or somatic growth. Thus, our findings suggest that the declining expression of these genes contributes to coordinate growth deceleration in multiple tissues. We next hypothesized that the coordinate decline in expression of these imprinted genes is caused by altered methylation and consequent silencing of the expressed allele. Contrary to this hypothesis, the methylation status of the promoter regions of Mest, Peg3, and Plagl1 did not change with age. Our findings suggest that a set of growth-regulating imprinted genes is expressed at high levels in multiple tissues in early postnatal life, contributing to rapid somatic growth, but that these genes are subsequently down-regulated in multiple tissues simultaneously, contributing to coordinate growth deceleration and cessation, thus imposing a fundamental limit on adult body size. C1 [Lui, Julian C.; Finkielstain, Gabriela P.; Barnes, Kevin M.; Baron, Jeffrey] NICHHD, NIH, Sect Growth & Dev, CRC, Bethesda, MD 20892 USA. RP Baron, J (reprint author), NICHHD, NIH, Sect Growth & Dev, CRC, Rm 1-3330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA. EM jeffrey.baron@nih.gov RI Lui, Chun Kin Julian/E-2253-2012 FU Intramural NIH HHS NR 43 TC 67 Z9 70 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 EI 1522-1490 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD JUL 1 PY 2008 VL 295 IS 1 BP R189 EP R196 DI 10.1152/ajpregu.00182.2008 PG 8 WC Physiology SC Physiology GA 323VY UT WOS:000257477700023 PM 18448610 ER PT J AU Chou, CL Yu, MJ Kassai, EM Morris, RG Hoffert, JD Wall, SM Knepper, MA AF Chou, Chung-Lin Yu, Ming-Jiun Kassai, Eliza M. Morris, Ryan G. Hoffert, Jason D. Wall, Susan M. Knepper, Mark A. TI Roles of basolateral solute uptake via NKCC1 and of myosin II in vasopressin-induced cell swelling in inner medullary collecting duct SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE cell volume; blebbistatin; cytoskeleton; kidney; inner medulla ID K-CL COTRANSPORTER; NA+-K+-2CL(-) COTRANSPORTER; NA-K-2CL COTRANSPORTER; WATER PERMEABILITY; PLASMA-MEMBRANES; UP-REGULATION; RAT; NA; TUBULES; RABBIT AB Collecting duct cells swell when exposed to arginine vasopressin (AVP) in the presence of a transepithelial osmolality gradient. We investigated the mechanisms of AVP-induced cell swelling in isolated, perfused rat inner medullary collecting ducts (IMCDs) using quantitative video microscopy and fluorescence-based measurements of transepithelial water transport. We tested the roles of transepithelial water flow, basolateral solute entry, and the cytoskeleton (actomyosin). When a transepithelial osmolality gradient was imposed by addition of NaCl to the bath, AVP significantly increased both water flux and cell height. When the osmolality gradient was imposed by addition of mannitol, AVP increased water flux but not cell height, suggesting that AVP-induced cell swelling requires a NaCl gradient and is not merely dependent on the associated water flux. Bumetanide (Na-K-2Cl cotransporter inhibitor) added to the bath markedly diminished the AVP-induced cell height increase. AVP-induced cell swelling was absent in IMCDs from NKCC1-knockout mice. In rat IMCDs, replacement of Na, K, or Cl in the peritubular bath caused significant cell shrinkage, consistent with a basolateral solute transport pathway dependent on all three ions. Immunocytochemistry using an antibody to NKCC1 confirmed basolateral expression in IMCD cells. The conventional nonmuscle myosin II inhibitor blebbistatin also diminished the AVP-induced cell height increase and cell shape change, consistent with a role for the actin cytoskeleton and myosin II. We conclude that the AVP-induced cell height increase is dependent on basolateral solute uptake via NKCC1 and changes in actin organization via myosin II, but is not dependent specifically on increased apical water entry. C1 [Chou, Chung-Lin; Yu, Ming-Jiun; Kassai, Eliza M.; Morris, Ryan G.; Hoffert, Jason D.; Knepper, Mark A.] NHLBI, Natl Inst Hlth, Bethesda, MD 20892 USA. [Wall, Susan M.] Emory Univ, Dept Med, Atlanta, GA 30322 USA. RP Knepper, MA (reprint author), NHLBI, Natl Inst Hlth, 10 Ctr Dr,Bldg 10,Rm 6N260, Bethesda, MD 20892 USA. EM knep@helix.nih.gov OI YU, MING-JIUN/0000-0003-0393-4696 FU Intramural NIH HHS; NHLBI NIH HHS [Z01-HL-001285]; NIDDK NIH HHS [P01 DK061521]; PHS HHS [P01-061521] NR 32 TC 14 Z9 15 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JUL PY 2008 VL 295 IS 1 BP F192 EP F201 DI 10.1152/ajprenal.00011.2008 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 322XW UT WOS:000257409600025 PM 18417545 ER PT J AU Lee, HT Chen, SWC Doetschman, TC Deng, C D'Agati, VD Kim, M AF Lee, H. Thomas Chen, Sean W. C. Doetschman, Thomas C. Deng, Chuxia D'Agati, Vivette D. Kim, Mihwa TI Sevoflurane protects against renal ischemia and reperfusion injury in mice via the transforming growth factor-beta(1) pathway SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE acute renal failure; inflammation; necrosis; SMAD3 ID RECEPTOR KNOCKOUT MICE; GROWTH-FACTOR-BETA; TGF-BETA; APOPTOTIC CELLS; TRANSFORMING GROWTH-FACTOR-BETA-1; PHOSPHATIDYLSERINE RECEPTOR; VOLATILE ANESTHETICS; CARDIAC-SURGERY; IN-VIVO; INFLAMMATION AB We previously demonstrated that several clinically utilized volatile anesthetics including sevoflurane protected against renal ischemia-reperfusion (IR) injury by reducing necrosis and inflammation in vivo. We also demonstrated that volatile anesthetics produced direct anti- necrotic and anti- inflammatory effects in cultured renal tubules via mechanisms involving the externalization of phosphatidylserine and subsequent release of transforming growth factor (TGF)-beta(1). In this study, we tested the hypothesis that volatile anesthetic- mediated renal protection requires TGF-beta(1) and SMAD3 signaling in vivo. We subjected TGF-beta(1) +/+, TGF-beta(1) +/-, SMAD3+/+, or SMAD3-/- mice to renal IR under anesthesia with pentobarbital sodium or with sevoflurane. Although TGF-beta(1) +/+ and SMAD3 +/+ mice were significantly protected against renal IR injury under sevoflurane anesthesia with reduced necrosis and inflammation, TGF-beta(1) +/+ mice and SMAD3 +/+ mice were not protected against renal IR with sevoflurane. Furthermore, a neutralizing TGF-beta(1) antibody blocked renal protection with sevoflurane in TGF-beta(1) +/+ mice. Sevoflurane caused nuclear translocation of SMAD3 and reduced the TNF-alpha-induced nuclear translocation of NF-kappa B in primary cultures of proximal tubules from TGF-beta(1) +/+ but not in TGF-beta(1) +/- mice. Finally, sevoflurane protected against necrosis induced with hydrogen peroxide in primary cultures of proximal tubules from TGF-beta(1) +/+ mice or SMAD3 +/+ mice but not in proximal tubules from TGF-beta(1) +/- or SMAD3 -/- mice. Therefore, we demonstrate in this study that sevoflurane- mediated renal protection in vivo requires the TGF- beta(1) -> SMAD3 signaling pathway. C1 [Lee, H. Thomas; Chen, Sean W. C.; Kim, Mihwa] Columbia Univ, Anesthesiol Res Labs, Dept Anesthesiol, Coll Phys & Surg, New York, NY 10032 USA. [D'Agati, Vivette D.] Columbia Univ, Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA. [Doetschman, Thomas C.] Univ Arizona, Dept Cell Biol & Anat, Tucson, AZ USA. [Deng, Chuxia] NIDDK, Genet Dev & Dis Branch, Natl Inst Hlth, Bethesda, MD USA. RP Lee, HT (reprint author), Columbia Univ, Anesthesiol Res Labs, Dept Anesthesiol, Coll Phys & Surg, P&S Box 46 PH-5,630 W 168th St, New York, NY 10032 USA. EM tl128@columbia.edu RI deng, chuxia/N-6713-2016 FU NIGMS NIH HHS [R01-GM-067081] NR 30 TC 33 Z9 37 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JUL PY 2008 VL 295 IS 1 BP F128 EP F136 DI 10.1152/ajprenal.00577.2007 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 322XW UT WOS:000257409600017 PM 18434384 ER PT J AU Baron, RC Rimer, BK Breslow, RA Coates, RJ Kerner, J Melillo, S Habarta, N Kalra, GP Chattopadhyay, S Wilson, KM Lee, NC Mullen, PD Coughlin, SS Briss, PA AF Baron, Roy C. Rimer, Barbara K. Breslow, Rosalind A. Coates, Ralph J. Kerner, Jon Melillo, Stephanie Habarta, Nancy Kalra, Geetika P. Chattopadhyay, Sajal Wilson, Katherine M. Lee, Nancy C. Mullen, Patricia Dolan Coughlin, Steven S. Briss, Peter A. CA Task Force Community Preventive Se TI Client-directed interventions to increase community demand for breast, cervical, and colorectal cancer screening SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; HEALTH MAINTENANCE ORGANIZATION; AFRICAN-AMERICAN WOMEN; MANAGED CARE PLAN; GENERAL-PRACTICE; LOW-INCOME; MAMMOGRAPHY UTILIZATION; PREVENTIVE-SERVICES; COST-EFFECTIVENESS; PATIENT REMINDERS AB Most major medical organizations recommend routine screening for breast, cervical, and colorectal cancers. Screening can lead to early detection of these cancers, resulting in reduced mortality. Yet not A people who should be screened are screened, either regularly or, in some cases, ever. This report presents the results of systematic reviews of effectiveness, applicability, economic efficiency, barriers to implementation, and other banns or benefits of interventions designed to increase screening for breast, cervical, and colorectal cancers by increasing community demand for these services. Evidence from these reviews indicates that screening for breast cancer (mammography) and cervical cancer (Pap test) has been effectively increased by use of client reminders, small media, and one-on-one education. Screening for colorectal cancer by fecal occult blood test has been increased effectively by use of client reminders and small media. Additional research is needed to determine whether client incentives, group education, and mass media are effective in increasing use of any of the three screening tests; whether one-on-one education increases screening for colorectal cancer; and whether any demand-enhancing interventions are effective in increasing the use of other colorectal cancer screening procedures (i.e., flexible sigmoidoscopy, colonoscopy, double contrast barium enema). Specific areas for further research are also suggested in this report. C1 [Baron, Roy C.; Melillo, Stephanie; Habarta, Nancy; Kalra, Geetika P.; Chattopadhyay, Sajal; Briss, Peter A.] CDC, Community Guide Branch, Natl Ctr Hlth Mkt, Atlanta, GA 30333 USA. [Breslow, Rosalind A.; Coates, Ralph J.; Wilson, Katherine M.; Lee, Nancy C.; Coughlin, Steven S.] CDC, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA. [Rimer, Barbara K.] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. [Kerner, Jon] NCI, NIH, Bethesda, MD 20892 USA. [Mullen, Patricia Dolan] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. RP Baron, RC (reprint author), CDC, Community Guide Branch, Natl Ctr Hlth Mkt, 1600 Clifton Rd NE,MS E-69, Atlanta, GA 30333 USA. EM rbaron@cdc.gov NR 161 TC 88 Z9 92 U1 4 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUL PY 2008 VL 35 IS 1 SU S BP S34 EP S55 DI 10.1016/j.amepre.2008.04.002 PG 22 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 317CO UT WOS:000256997200008 PM 18541187 ER PT J AU Baron, RC Rimer, BK Coates, RJ Kerner, J Kalra, GP Melillo, S Habarta, N Wilson, KM Chattopadhyay, S Leeks, K AF Baron, Roy C. Rimer, Barbara K. Coates, Ralph J. Kerner, Jon Kalra, Geetika P. Melillo, Stephanie Habarta, Nancy Wilson, Katherine M. Chattopadhyay, Sajal Leeks, Kimberly CA Task Force Community Preventive Se TI Client-directed interventions to increase community access to breast, cervical, and colorectal cancer screening - A systematic review SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Review ID HEALTH INTERVIEW SURVEY; OCCULT BLOOD-TEST; PREVENTIVE-SERVICES; REPEAT MAMMOGRAPHY; RANDOMIZED-TRIAL; GENERAL-PRACTICE; AMERICAN WOMEN; CLINICAL-TRIAL; EDUCATION; PREVALENCE AB Most major medical organizations recommend routine screening for breast, cervical, and colorectal cancers. Screening can lead to early detection of these cancers, resulting in reduced mortality. Yet not all people who should be screened are screened, either regularly or, in some cases, ever. This report presents the results of systematic reviews of effectiveness, applicability, economic efficiency, barriers to implementation, and other harms or benefits of interventions designed to increase screening for breast, cervical, and colorectal cancers by increasing community access to these services. Evidence from these reviews indicates that screening for breast cancer (by mammography) has been increased effectively by reducing structural barriers and by reducing out-of pocket client costs, and that screening for colorectal cancer (by fecal occult blood test) has been increased effectively by reducing structural barriers. Additional research is needed to determine whether screening for cervical cancer (by Pap test) can be increased by reducing structural barriers and by reducing out-of-pocket costs, whether screening for colorectal cancer (fecal occult blood test) can be increased by reducing out-of-pocket costs, and whether these interventions are effective in increasing the use of other colorectal cancer screening procedures (i.e., flexible sigmoidoscopy, colonoscopy, double contrast barium enema). Specific areas for further research are also suggested in this report. C1 [Baron, Roy C.; Kalra, Geetika P.; Melillo, Stephanie; Habarta, Nancy; Chattopadhyay, Sajal; Leeks, Kimberly] CDC, Community Guide Branch, Natl Ctr Hlth Mkt, Atlanta, GA 30333 USA. [Coates, Ralph J.; Wilson, Katherine M.] CDC, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA. [Rimer, Barbara K.] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. [Kerner, Jon] NCI, NIH, Bethesda, MD 20892 USA. RP Baron, RC (reprint author), CDC, Community Guide Branch, Natl Ctr Hlth Mkt, 1600 Clifton Rd NE,MS E-69, Atlanta, GA 30333 USA. EM rbaron@cdc.gov OI Kerner, Jon/0000-0002-8792-3830 NR 41 TC 68 Z9 70 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUL PY 2008 VL 35 IS 1 SU S BP S56 EP S66 DI 10.1016/j.amepre.2008.04.001 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 317CO UT WOS:000256997200009 PM 18541188 ER PT J AU Baron, RC Rimer, BK Coates, RJ Kerner, J Mullen, PD Chattopadhyay, S Briss, PA AF Baron, Roy C. Rimer, Barbara K. Coates, Ralph J. Kerner, Jon Mullen, Patricia Dolan Chattopadhyay, Sajal Briss, Peter A. CA Task Force Community Preventive Se TI Methods for conducting systematic reviews of evidence on effectiveness and economic efficiency of interventions to increase screening for breast, cervical, and colorectal cancers SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID COMMUNITY-PREVENTIVE-SERVICES C1 [Baron, Roy C.; Chattopadhyay, Sajal; Briss, Peter A.] CDC, Community Guide Branch, Natl Ctr Hlth Mkt, Atlanta, GA 30333 USA. [Coates, Ralph J.] CDC, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA. [Rimer, Barbara K.] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. [Kerner, Jon] NCI, NIH, Bethesda, MD 20892 USA. [Mullen, Patricia Dolan] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. RP Baron, RC (reprint author), CDC, Community Guide Branch, Natl Ctr Hlth Mkt, 1600 Clifton Rd NE,MS E-69, Atlanta, GA 30333 USA. EM rbaron@cdc.gov OI Kerner, Jon/0000-0002-8792-3830 NR 18 TC 20 Z9 22 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUL PY 2008 VL 35 IS 1 SU S BP S26 EP S33 DI 10.1016/j.amepre.2008.04.003 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 317CO UT WOS:000256997200007 PM 18541185 ER PT J AU Breslow, RA Rimer, BK Baron, RC Coates, RJ Kerner, J Wilson, KM Lee, NC Mullen, PD Coughlin, SS Briss, PA AF Breslow, Rosalind A. Rimer, Barbara K. Baron, Roy C. Coates, Ralph J. Kerner, Jon Wilson, Katherine M. Lee, Nancy C. Mullen, Patricia Dolan Coughlin, Steven S. Briss, Peter A. TI Introducing the community guide's reviews of evidence on interventions to increase screening for breast, cervical, and colorectal cancers SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Editorial Material ID PREVENT SKIN-CANCER; ULTRAVIOLET-RADIATION; VACCINATION COVERAGE; SYSTEMATIC REVIEWS; REDUCING EXPOSURE; SERVICES; RECOMMENDATIONS; STATEMENT; QUALITY; ADULTS C1 [Baron, Roy C.] CDC, Community Guide Branch, Atlanta, GA 30333 USA. [Breslow, Rosalind A.; Coates, Ralph J.; Wilson, Katherine M.; Lee, Nancy C.; Coughlin, Steven S.] Div Canc Prevent & Control, Atlanta, GA USA. [Kerner, Jon] NCI, NIH, Bethesda, MD 20892 USA. [Rimer, Barbara K.] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. [Mullen, Patricia Dolan] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. RP Baron, RC (reprint author), CDC, Community Guide Branch, 1600 Clifton Rd NE,MS E-69, Atlanta, GA 30333 USA. EM rbaron@cdc.gov OI Kerner, Jon/0000-0002-8792-3830 NR 45 TC 11 Z9 11 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUL PY 2008 VL 35 IS 1 SU S BP S14 EP S20 DI 10.1016/j.amepre.2008.04.005 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 317CO UT WOS:000256997200005 PM 18541183 ER PT J AU Sabatino, SA Habarta, N Baron, RC Coates, RJ Rimer, BK Kerner, J Coughlin, SS Kalra, GP Chattopadhyay, S AF Sabatino, Susan A. Habarta, Nancy Baron, Roy C. Coates, Ralph J. Rimer, Barbara K. Kerner, Jon Coughlin, Steven S. Kalra, Geetika P. Chattopadhyay, Sajal CA Task Force Community Preventive Se TI Interventions to increase recommendation and delivery of screening for breast, cervical, and colorectal cancers by healthcare providers - Systematic reviews of provider assessment and feedback and provider incentives SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID COMMUNITY-PREVENTIVE-SERVICES; PHYSICIAN COMPLIANCE; MAMMOGRAPHY; METAANALYSIS; PERSPECTIVE; POPULATION; GUIDELINES; MEDICINE; PERFORM; REPEAT AB Most major medical organizations recommend routine screening for breast, cervical, and colorectal cancers. Screening can lead to early detection of these cancers, resulting in reduced mortality. Yet not all people who should be screened are screened, either regularly or, in some cases, ever. This report presents results of systematic reviews of effectiveness, applicability, economic efficiency, barriers to implementation, and other harms or benefits of two provider-directed intervention approaches to increase screening for breast, cervical, and colorectal cancers. These approaches, provider assessment and feedback, and provider incentives encourage providers to deliver screening services at appropriate intervals. Evidence in these reviews indicates that provider assessment and feedback interventions can effectively increase screening by mammography, Pap test, and fecal occult blood test. Health plans, healthcare systems, and cancer control coalitions should consider such evidence-based findings when implementing interventions to increase screening use. Evidence was insufficient to determine the effectiveness of provider incentives in increasing use of any of these tests. Specific areas for further research are Suggested in this report, including the need for additional research to determine whether provider incentives are effective in increasing use of any of these screening tests, and whether assessment and feedback interventions are effective in increasing other tests for colorectal cancer (i.e., flexible sigmoidoscopy, colonoscopy, or double-contrast barium enema). C1 [Sabatino, Susan A.; Coates, Ralph J.; Coughlin, Steven S.] CDC, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA. [Habarta, Nancy; Baron, Roy C.; Kalra, Geetika P.; Chattopadhyay, Sajal] CDC, Community Guide Branch, Natl Ctr Hlth Mkt, Atlanta, GA 30333 USA. [Rimer, Barbara K.] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. [Kerner, Jon] NCI, NIH, Bethesda, MD 20892 USA. RP Sabatino, SA (reprint author), CDC, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, 1600 Clifton Rd,MS K-53, Atlanta, GA 30333 USA. EM SSabatino@cdc.gov OI Kerner, Jon/0000-0002-8792-3830 NR 47 TC 71 Z9 74 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUL PY 2008 VL 35 IS 1 SU S BP S67 EP S74 DI 10.1016/j.amepre.2008.04.008 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 317CO UT WOS:000256997200010 PM 18541190 ER PT J AU Yabroff, KR AF Yabroff, K. Robin TI Interventions to improve cancer screening - Commentary from a health services research perspective SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Editorial Material ID COLORECTAL-CANCER; CERVICAL-CANCER; BREAST-CANCER; UNITED-STATES; TASK-FORCE; CARE; ACCESS; QUALITY; WOMEN C1 [Yabroff, K. Robin] NCI, Hlth Services & Econ Branch, Applied Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Yabroff, KR (reprint author), NCI, Hlth Services & Econ Branch, Applied Res Program, Div Canc Control & Populat Sci, Executive Plaza N,Room 4005,6130 Execut Blvd,MSC, Bethesda, MD 20892 USA. EM yabroffr@mail.nih.gov OI Yabroff, K. Robin/0000-0003-0644-5572 NR 20 TC 9 Z9 10 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUL PY 2008 VL 35 IS 1 SU S BP S6 EP S9 DI 10.1016/j.amepre.2008.04.006 PG 4 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 317CO UT WOS:000256997200003 PM 18541189 ER PT J AU Sultzer, DL Davis, SM Tariot, PN Dagerman, KS Lebowitz, BD Lyketsos, CG Rosenheck, RA Hsiao, JK Lieberman, JA Schneider, LS AF Sultzer, David L. Davis, Sonia M. Tariot, Pierre N. Dagerman, Karen S. Lebowitz, Barry D. Lyketsos, Constantine G. Rosenheck, Robert A. Hsiao, John K. Lieberman, Jeffrey A. Schneider, Lon S. CA CATIE-AD Study Grp TI Clinical symptom responses to atypical antipsychotic medications in Alzheimer's disease: Phase 1 outcomes from the CATIE-AD effectiveness trial SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID INTERVENTION EFFECTIVENESS CATIE; RATING-SCALE BPRS; NEUROPSYCHIATRIC SYMPTOMS; DEMENTIA; MANAGEMENT; INVENTORY; PSYCHOSIS; DONEPEZIL; RISK AB Objective: The study measured the effects of atypical antipsychotics on psychiatric and behavioral symptoms in patients with Alzheimer's disease and psychosis or agitated behavior. Method: The Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) Alzheimer's disease effectiveness study included 421 outpatients with Alzheimer's disease and psychosis or agitated/aggressive behavior. Patients were assigned randomly to masked, flexible-dose treatment with olanzapine, quetiapine, risperidone, or placebo for up to 36 weeks. Patients could be randomly reassigned to a different medication at the clinician's discretion, which ended phase 1. Psychiatric and behavioral symptoms, functioning, cognition, care needs, and quality of life were measured at regular intervals. Results: In relation to placebo, the last observation in phase 1 showed greater improvement with olanzapine or risperidone on the Neuropsychiatric Inventory total score, risperidone on the Clinical Global Impression of Changes, olanzapine and risperidone on the Brief Psychiatric Rating Scale (BPRS) hostile suspiciousness factor, and risperidone on the BPRS psychosis factor. There was worsening with olanzapine on the BPRS withdrawn depression factor. Among patients continuing phase 1 treatment at 12 weeks, there were no significant differences between antipsychotics and placebo on cognition, functioning, care needs, or quality of life, except for worsened functioning with olanzapine compared to placebo. Conclusion: In this descriptive analysis of outpatients with Alzheimer's disease in usual care settings, some clinical symptoms improved with atypical antipsychotics. Antipsychotics may be more effective for particular symptoms, such as anger, aggression, and paranoid ideas. They do not appear to improve functioning, care needs, or quality of life. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Gero Neuropsychiat Div, Los Angeles, CA USA. Quintiles, Res Triangle Pk, NC USA. Univ So Calif, Keck Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA. Banner Alzheimers Inst, Phoenix, AZ USA. Univ Calif San Diego, Sch Med, Div Geriatr Psychiat, La Jolla, CA 92093 USA. Johns Hopkins Bayview Med Ctr, Dept Psychiat, Baltimore, MD USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. VA Connecticut Hlth Care Syst, New Haven, CT USA. NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Sultzer, DL (reprint author), 3 South,116AE,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM dsultzer@ucla.edu OI Adler, Lawrence/0000-0002-6619-2493 FU NIMH NIH HHS [N01 MH90001, N01 MH-9001] NR 34 TC 120 Z9 125 U1 2 U2 14 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUL PY 2008 VL 165 IS 7 BP 844 EP 854 DI 10.1176/appi.ajp.2008.07111779 PG 11 WC Psychiatry SC Psychiatry GA 321PX UT WOS:000257320100013 PM 18519523 ER PT J AU Grillon, C Lissek, S Rabin, S McDowell, D Dvir, S Pine, DS AF Grillon, Christian Lissek, Shmuel Rabin, Stephanie McDowell, Dana Dvir, Sharone Pine, Daniel S. TI Increased anxiety during anticipation of unpredictable but not predictable aversive stimuli as a psychophysiologic marker of panic disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID FEAR-POTENTIATED STARTLE; BED NUCLEUS; STRIA TERMINALIS; PERSPECTIVE; AGORAPHOBIA; RESPONSES; STRESS; HUMANS; CONSEQUENCES; ENVIRONMENT AB Objective: Predictability is a fundamental modulator of anxiety in that the ability to predict aversive events mitigates anxious responses. In panic disorder, persistent symptoms of anxiety are caused by anticipation of the next uncued (unpredictable) panic attack. The authors tested the hypothesis that elevated anxious reactivity, specifically toward unpredictable aversive events, is a psychophysiological correlate of panic disorder. Method: Participants were exposed to one condition in which predictable aversive stimuli were signaled by a cue, a second condition in which aversive stimuli were administered unpredictably, and a third condition in which no aversive stimuli were anticipated. Startle was used to assess anxious responses to cues and contexts. Results: Relative to healthy comparison subjects, patients with panic disorder displayed equivalent levels of fear-potentiated startle to the threat cue but elevated startle potentiation in the context of the unpredictable condition. Conclusions: Patients with panic disorder are overly sensitive to unpredictable aversive events. This vulnerability could be either a premorbid trait marker of the disorder or an acquired condition caused by the experience of uncued panic attacks. As a premorbid trait, vulnerability to unpredictability could be etiologically related to panic disorder by sensitizing an individual to danger, ultimately leading to intense fear/alarm responses to mild threats. As an acquired characteristic, such vulnerability could contribute to the maintenance and worsening of panic disorder symptoms by increasing anticipatory anxiety. C1 [Grillon, Christian; Lissek, Shmuel; Rabin, Stephanie; McDowell, Dana; Dvir, Sharone; Pine, Daniel S.] NIMH, MAP, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Grillon, C (reprint author), NIMH, MAP, Mood & Anxiety Disorders Program, 15K N Dr,Bldg 15K,Rm 113,MSC 2670, Bethesda, MD 20892 USA. EM Christian.grillon@nih.gov OI Rabin, Stephanie/0000-0002-8282-0867 FU Intramural NIH HHS [Z01 MH002798-06] NR 41 TC 111 Z9 112 U1 2 U2 16 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUL PY 2008 VL 165 IS 7 BP 898 EP 904 DI 10.1176/appi.ajp.2007.07101581 PG 7 WC Psychiatry SC Psychiatry GA 321PX UT WOS:000257320100019 PM 18347001 ER PT J AU Murabito, JM Pencina, MJ Zhu, L Kelly-Hayes, M Shrader, P D'Agostino, RB AF Murabito, Joanne M. Pencina, Michael J. Zhu, Lei Kelly-Hayes, Margaret Shrader, Peter D'Agostino, Ralph B., Sr. TI Temporal trends in self-reported functional limitations and physical disability among the community-dwelling elderly population: The Framingham Heart Study SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID OLD-AGE DISABILITY; UNITED-STATES; MOBILITY DISABILITY; MORBIDITY; HEALTH; ADULTS; RELIABILITY; PERFORMANCE; PREVALENCE; AMERICANS AB Objectives. We sought to determine change in the prevalence of functional limitations and physical disability among the community-dwelling elderly population across 3 decades. Methods. We studied original participants of the Framingham Heart Study, aged 79 to 88 years, at examination 15 (1977-1979; 177 women, 103 men), examination 20 (11988-11990,159 women, 98 men) and examination 25 (1997-1999; 174 women, 119 men). Self-reported functional limitation was defined using the Nagi scale, and physical disability was defined using the Rosow-Breslau and Katz scales. Results. Functional limitations declined across examinations from 74.6% to 60.5% to 37.9% (P <.601) among women and from 54.2% to 37.8% to 27.8% (P <.001) among men. Physical disability declined from 74.5% to 48.5% to 34.6% (P <.001) among women and 42.3% to 33.3% to 22.8% (P=.009) among men. Among women, improvements in functional limitations (P=.05) were greater from examination 20 to 25, whereas for physical disability (P=.02), improvements were greater from examination 15 to 20. Improvements in function were constant across the 3 examinations in men. Conclusions. Among community-dwelling elders, the prevalence of functional limitations and physical disability declined significantly in both women and men from the 1970s to the 1990s. This may in part be due to improvements in technological devices used to maintain independence. Further work is needed to identify the underlining causes of the decline so preventative measures can be established that promote independence for the elderly population. C1 [Murabito, Joanne M.; Pencina, Michael J.; Kelly-Hayes, Margaret; D'Agostino, Ralph B., Sr.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Kelly-Hayes, Margaret] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Pencina, Michael J.; Zhu, Lei; Shrader, Peter; D'Agostino, Ralph B., Sr.] Boston Univ, Sch Med, Dept Math & Stat, Boston, MA 02118 USA. RP Murabito, JM (reprint author), 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM murabito@bu.edu OI Murabito, Joanne/0000-0002-0192-7516 FU NHLBI NIH HHS [N01 HC025195, N01-HC-25195, N01HC25195]; NIA NIH HHS [5R01-AG08122, R01 AG008122, R01 AG008122-20]; NINDS NIH HHS [R01 NS017950, 5R01-NS17950, R01 NS017950-28] NR 42 TC 29 Z9 29 U1 0 U2 6 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUL PY 2008 VL 98 IS 7 BP 1256 EP 1262 DI 10.2105/AJPH.2007.128132 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 319ZE UT WOS:000257202700024 PM 18511716 ER PT J AU Voltz, JW Card, JW Carey, MA DeGraff, LM Ferguson, CD Flake, GP Bonner, JC Korach, KS Zeldin, DC AF Voltz, James W. Card, Jeffrey W. Carey, Michelle A. DeGraff, Laura M. Ferguson, Catherine D. Flake, Gordon P. Bonner, James C. Korach, Kenneth S. Zeldin, Darryl C. TI Male sex hormones exacerbate lung function impairment after bleomycin-induced pulmonary fibrosis SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE fibrosis; bleomycin; sex; respiratory mechanics ID AIRWAY RESPONSIVENESS; GENDER-DIFFERENCES; MOLECULAR-CLONING; HYDROLASE; DISEASE; MICE; PHYSIOLOGY; DEFICIENCY; MORTALITY; LESSONS AB The roles of sex hormones as modulators of lung function and disease have received significant attention as differential sex responses to various lung insults have been recently reported. The present study used a bleomycin-induced pulmonary fibrosis model in C57BL/6 mice to examine potential sex differences in physiological and pathological outcomes. Endpoints measured included invasive lung function assessment, immunological response, lung collagen deposition, and a quantitative histological analysis of pulmonary fibrosis. Male mice had significantly higher basal static lung compliance than female mice (P < 0.05) and a more pronounced decline in static compliance after bleomycin administration when expressed as overall change or percentage of baseline change (P < 0.05). In contrast, there were no significant differences between the sexes in immune cell infiltration into the lung or in total lung collagen content after bleomycin. Total lung histopathology scores measured using the Ashcroft method did not differ between the sexes, while a quantitative histopathology scoring system designed to determine where within the lung the fibrosis occurred indicated a tendency toward more fibrosis immediately adjacent to airways in bleomycin-treated male versus female mice. Furthermore, castrated male mice exhibited a female-like response to bleomycin while female mice given exogenous androgen exhibited a male-like response. These data indicate that androgens play an exacerbating role in decreased lung function after bleomycin administration, and traditional measures of fibrosis may miss critical differences in lung function between the sexes. Sex differences should be carefully considered when designing and interpreting experimental models of pulmonary fibrosis in mice. C1 [Voltz, James W.; Card, Jeffrey W.; Carey, Michelle A.; DeGraff, Laura M.; Ferguson, Catherine D.; Flake, Gordon P.; Korach, Kenneth S.; Zeldin, Darryl C.] NIEHS, NIH, Div Intramural Res, Res Triangle Pk, NC 27709 USA. [Bonner, James C.] N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA. RP Zeldin, DC (reprint author), NIEHS, NIH, Div Intramural Res, 111 TW Alexander Dr,Bldg 101,Room D236, Res Triangle Pk, NC 27709 USA. EM zeldin@niehs.nih.gov OI Korach, Kenneth/0000-0002-7765-418X FU Intramural NIH HHS; NIEHS NIH HHS [1R21ES015801-01] NR 40 TC 27 Z9 28 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1044-1549 EI 1535-4989 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD JUL PY 2008 VL 39 IS 1 BP 45 EP 52 DI 10.1165/rcmb.2007-0340OC PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 317RP UT WOS:000257037600006 PM 18276795 ER PT J AU Summers, RM Handwerker, LR Pickhardt, PJ Van Uitert, RL Deshpande, KK Yeshwant, S Yao, JH Franaszek, M AF Summers, Ronald M. Handwerker, Laurie R. Pickhardt, Perry J. Van Uitert, Robert L. Deshpande, Keshav K. Yeshwant, Srinath Yao, Jianhua Franaszek, Marek TI Performance of a previously validated CT colonography computer-aided detection system in a new patient population SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE automated detection; colon; colon cancer; CT; image processing; virtual imaging ID TOMOGRAPHIC VIRTUAL COLONOSCOPY; ASSISTED READER SOFTWARE; POLYP DETECTION; COLORECTAL NEOPLASIA; COLONIC POLYPS; 2ND READER; EXPERIENCE; LESS AB OBJECTIVE. A computer-aided detection (CAD) system with high sensitivity in the detection of adenomatous polyps in varied CT colonography (CTC) data sets increases the utility of CAD in the clinical setting. The purpose of this study was to evaluate the stand-alone performance of an existing CAD system with a new set of CTC data from screening patients at an institution and geographic location different from those at which the CAD system was trained. MATERIALS AND METHODS. CTC data were collected from the records of 104 patients undergoing screening for colorectal neoplasia. Most of the patients were at average risk, had CTC findings suggestive of polyps, and underwent colonoscopy. Patients underwent cathartic bowel preparation, were given an oral contrast agent, and underwent imaging in the prone and supine positions. The patients had 86 adenomas confirmed at same-day optical colonoscopy; 47 of these tumors were 10 mm in diameter or larger, and 39 measured 6-9 mm. The CTC data were analyzed with an existing CAD system for colonography that was trained with previously acquired data. In a previous non-polyp-enriched screening cohort, the stand-alone performance of the CAD system was 93.3% (28/30) sensitivity for adenomatous polyps 10 mm or larger, 51.1% (47/92) sensitivity for adenomas 6-9 mm, and a mean false-positive rate of 8.6 per patient. Sensitivity comparisons were made with findings in the previous study. RESULTS. The CAD system had per-polyp sensitivities of 91.5% (43/47; 95% CI, 78.7-97.2%; p = 1.0) for adenomas 10 mm or larger and 82.1% (32/39; 65.9-91.9%; p = 0.0009) for adenomas 6-9 mm. The per- patient sensitivities were 97.6% (40/41; 85.6-99.9%; p = 0.6) for patients with adenomas 10 mm or larger and 82.4% (28/34; 64.8-92.6%; p = 0.047) for patients with adenomas 6-9 mm. The mean and median false-positive rates were 9.6 +/- 9.6 and 7.0 per patient, respectively. Common reasons for CAD misses ( false-negative findings) were the presence of adherent contrast medium, flat adenomas, and adenomas located on or adjacent to normal colonic folds. In a random sample, 72.5% (29/40) of false-positive findings were attributable to folds or residual feces. CONCLUSION. The CAD system evaluated has a high level of performance in the detection of adenomatous polyps with CTC data from a polyp-enriched cohort different from that used to train the system. C1 [Summers, Ronald M.; Handwerker, Laurie R.; Van Uitert, Robert L.; Deshpande, Keshav K.; Yeshwant, Srinath; Yao, Jianhua; Franaszek, Marek] NIH, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. [Pickhardt, Perry J.] Univ Wisconsin, Dept Radiol, Madison, WI 53706 USA. RP Summers, RM (reprint author), NIH, Ctr Clin, Dept Diagnost Radiol, Bldg 10,Rm 1C368X,MSC 1182, Bethesda, MD 20892 USA. EM rms@nih.gov FU Intramural NIH HHS NR 29 TC 27 Z9 28 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 2008 VL 191 IS 1 BP 168 EP 174 DI 10.2214/AJR.07.3354 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 315OV UT WOS:000256890200029 PM 18562741 ER PT J AU Lenfant, C AF Lenfant, Claude TI Can prevention of hypertension work? SO AMERICAN JOURNAL OF THERAPEUTICS LA English DT Article DE prevention; weight reduction; lifestyle modification ID WEIGHT-LOSS INTERVENTION; LIFE-STYLE MODIFICATION; HIGH BLOOD-PRESSURE; SODIUM REDUCTION; NONPHARMACOLOGIC INTERVENTIONS; DIETARY-SODIUM; CLINICAL-TRIAL; PHASE-II AB In this article, the clinical trials that have most effectively demonstrated the effectiveness of hypertension nonpharmacologic prevention interventions are presented and discussed. Thus, data from weight reduction, dietary interventions, and lifestyle modifications are shown and discussed. It is concluded that these interventions lead to control of hypertension either by themselves or in association with pharmacologic interventions. Over the years, many controlled clinical trials have demonstrated the efficacy of pharmacologic treatment of hypertension. However, such treatment has its shortcomings. First, it usually requires a lifelong commitment to therapy because, although this approach can control hypertension and reduce its consequences, it does not cure the condition. Next, the cost of pharmacologic interventions can be very high and, thus, prohibitive for poorer individuals and nations. In addition, many patients experience problems with compliance and adherence, which almost certainly contribute to the low level of hypertension control that is so widely observed. Finally, the pharmacologic approach requires a strong commitment by public health officials for detection and treatment of hypertension if there is to be any hope of limiting this condition's impact. All of these negative considerations are compounded by the fact that the prevalence of hypertension is increasing worldwide. For all these reasons, nonpharmacologic interventions should be implemented to prevent or delay the occurrence of hypertension. C1 [Lenfant, Claude] NHLBI, NIH, Bethesda, MD 20892 USA. RP Lenfant, C (reprint author), POB 83027, Gaithersburg, MD 20883 USA. EM lenfantc@prodigy.net NR 16 TC 1 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1075-2765 J9 AM J THER JI Am. J. Ther. PD JUL-AUG PY 2008 VL 15 IS 4 BP 334 EP 339 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 331KK UT WOS:000258010900009 PM 18645336 ER PT J AU Lenfant, C AF Lenfant, Claude TI Do sleep disorders have an impact on blood pressure? SO AMERICAN JOURNAL OF THERAPEUTICS LA English DT Article DE hypertension; sleep disorders; obesity; risk factor interdependence ID POSITIVE AIRWAY PRESSURE; ESSENTIAL-HYPERTENSION; APNEA SYNDROME; WEIGHT; ASSOCIATION; POPULATION; PREVALENCE; OBESITY; BURDEN; HEALTH AB In this article, the relationship, perhaps interdependence, between sleep-disordered breathing, hypertension, and obesity is discussed. There is strong evidence that sleep-disordered breathing and hypertension are related. On the one hand, the prevalence of hypertension increases with the number of apnea-hypopnea episodes per hour of sleep, whereas on the other hand, treating sleep-disordered breathing reduces hypertension. It has also been shown that this relationship between sleep-disordered breathing and hypertension is stronger in individuals with a high body mass index. Thus, it is concluded that in individuals presenting with hypertension, sleep-disordered breathing, or increased weight, the two other variables must be investigated and treated if present. C1 [Lenfant, Claude] NHLBI, NIH, Bethesda, MD 20892 USA. RP Lenfant, C (reprint author), POB 83027, Gaithersburg, MD 20883 USA. EM lenfantc@prodigy.net NR 23 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1075-2765 J9 AM J THER JI Am. J. Ther. PD JUL-AUG PY 2008 VL 15 IS 4 BP 345 EP 350 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 331KK UT WOS:000258010900011 PM 18645338 ER PT J AU Nathan, SD Shlobin, OA Ahmad, S Barnett, SD Burton, NA Gladwin, MT Machado, RF AF Nathan, S. D. Shlobin, O. A. Ahmad, S. Barnett, S. D. Burton, N. A. Gladwin, M. T. Machado, R. F. TI Pulmonary hypertension in patients with Bronchiolitis Obliterans Syndrome listed for retransplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE bronchiolitis obliterans; chronic rejection; hypertension; lung transplantation; pulmonary ID HEART-LUNG TRANSPLANTATION; ARTERIAL-HYPERTENSION; FIBROSIS; DISEASE; RECIPIENTS; OUTCOMES; BETA AB Bronchiolitis Obliterans Syndrome (BOS) is a major cause of morbidity and mortality post-lung transplantation. Pulmonary hypertension (PH) may complicate the course of patients with advanced lung disease. We sought to characterize the prevalence of PH in patients with BOS. We performed a retrospective analysis of lung transplant recipients with BOS relisted for transplantation with the United Network for Organ Sharing (UNOS). Right heart catheterization (RHC) data were required for analysis. Eighty patients with BOS qualified for the analysis. PH was present in 32.5% of patients with an average mean pulmonary artery pressure (mPAP) of 32.3 mmHg (range: 26-63 mmHg). Of these, 42.3% had an elevated pulmonary capillary wedge pressure. There was no difference in PH prevalence between bilateral (26.5%) and single lung recipients (41.9%), nor did it differ by primary disease. There was no correlation between pulmonary function data and the presence or severity of PH. There was no difference in oxygen requirements or 6-min walk distance between patients with and without PH. This is the first report of PH in patients with BOS. Many of these cases occur in association with diastolic dysfunction. Although no impact on functional status or outcomes was discerned, further studies appear warranted. C1 [Nathan, S. D.; Shlobin, O. A.; Ahmad, S.; Barnett, S. D.; Burton, N. A.] Inova Fairfax Hosp, Inova Adv Lung Dis & Transplant Program, Falls Church, VA USA. [Gladwin, M. T.; Machado, R. F.] NHLBI, Vasc Med Branch, Bethesda, MD 20892 USA. RP Nathan, SD (reprint author), Inova Fairfax Hosp, Inova Adv Lung Dis & Transplant Program, Falls Church, VA USA. EM Steven.nathan@inova.org FU PHS HHS [234-2005-370011 C] NR 24 TC 11 Z9 12 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUL PY 2008 VL 8 IS 7 BP 1506 EP 1511 DI 10.1111/j.1600-6143.2008.02277.x PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA 324WJ UT WOS:000257549800021 PM 18510629 ER PT J AU Sander, LC Putzbach, K Nelson, BC Rimmer, CA Bedner, M Thomas, JB Porter, BJ Wood, LJ Schantz, MM Murphy, KE Sharpless, KE Wise, SA Yen, JH Siitonen, PH Evans, RL Pho, AN Roman, MC Betz, JM AF Sander, L. C. Putzbach, K. Nelson, B. C. Rimmer, C. A. Bedner, M. Thomas, J. Brown Porter, B. J. Wood, L. J. Schantz, M. M. Murphy, K. E. Sharpless, K. E. Wise, S. A. Yen, J. H. Siitonen, P. H. Evans, R. L. Pho, A. Nguyen Roman, M. C. Betz, J. M. TI Certification of standard reference materials containing bitter orange SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Article; Proceedings Paper CT 11th International Symposium on Biological and Environmental Reference Materials (BERM 11) CY OCT 29-NOV 02, 2007 CL Tsukuba, JAPAN DE reference materials; natural products; organic compounds; high-performance liquid chromatography; foods/beverages ID PERFORMANCE LIQUID-CHROMATOGRAPHY; DIETARY-SUPPLEMENTS; EPHEDRINE ALKALOIDS; MASS-SPECTROMETRY; ADRENERGIC AMINES; CITRUS-AURANTIUM; FLUORESCENCE DETECTION; ULTRAVIOLET DETECTION; STATIONARY-PHASE; SYNEPHRINE AB A suite of three dietary supplement standard reference materials (SRMs) containing bitter orange has been developed, and the levels of five alkaloids and caffeine have been measured by multiple analytical methods. Synephrine, octopamine, tyramine, N-methyltyramine, hordenine, total alkaloids, and caffeine were determined by as many as six analytical methods, with measurements performed at the National Institute of Standards and Technology and at two collaborating laboratories. The methods offer substantial independence, with two types of extractions, two separation methods, and four detection methods. Excellent agreement was obtained among the measurements, with data reproducibility for most methods and analytes better than 5% relative standard deviation. The bitter-orange-containing dietary supplement SRMs are intended primarily for use as measurement controls and for use in the development and validation of analytical methods. C1 [Sander, L. C.; Putzbach, K.; Nelson, B. C.; Rimmer, C. A.; Bedner, M.; Thomas, J. Brown; Porter, B. J.; Wood, L. J.; Schantz, M. M.; Murphy, K. E.; Sharpless, K. E.; Wise, S. A.] Natl Inst Stand & Technol, Chem Sci & Technol Lab, Gaithersburg, MD 20899 USA. [Yen, J. H.] Natl Inst Stand & Technol, Informat Technol Lab, Gaithersburg, MD 20899 USA. [Siitonen, P. H.; Evans, R. L.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Roman, M. C.] ChromaDex Inc, Res & Dev, Clearwater, FL 33760 USA. [Betz, J. M.] Natl Inst Hlth, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Sander, LC (reprint author), Natl Inst Stand & Technol, Chem Sci & Technol Lab, 100 Bur Dr,MS 8392, Gaithersburg, MD 20899 USA. EM lane.sander@nist.gov NR 24 TC 26 Z9 26 U1 0 U2 6 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD JUL PY 2008 VL 391 IS 6 BP 2023 EP 2034 DI 10.1007/s00216-008-2074-0 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 319YF UT WOS:000257200200006 PM 18425642 ER PT J AU Pipkorn, P Costantini, C Reynolds, C Wall, M Drake, M Sanico, A Proud, D Togias, A AF Pipkorn, Patrik Costantini, Candy Reynolds, Curt Wall, Michael Drake, Margaret Sanico, Alvin Proud, David Togias, Alkis TI The effects of the nasal antihistamines olopatadine and azelastine in nasal allergen provocation SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID MAST-CELL ACTIVATION; MEDIATOR RELEASE; HISTAMINE-RELEASE; LEUKOTRIENE SYNTHESIS; RHINITIS; CHALLENGE; INHIBITION; SPRAY; EFFICACY; CETIRIZINE AB Background: Olopatadine, an antihistamine used in allergic conjunctivitis, is under development as a nasal preparation for the treatment of allergic rhinitis. Objectives: To evaluate the efficacy of olopatadine in suppressing symptoms and biomarkers of the immediate reaction induced by nasal allergen provocation and to compare olopatadine with azelastine in the same model. Methods: The study was approved by the Johns Hopkins University institutional review board, and all subjects gave written consent. We studied 20 asymptomatic subjects with seasonal allergic rhinitis. The study had 2 randomized, double-blind, placebo-controlled, crossover phases that evaluated 2 concentrations of olopatadine, 0.1% and 0.2%. In a third exploratory phase, olopatadine, 0.1%, was compared with topical azelastine, 0.1%, in a patient-masked design. Efficacy variables were the allergen-induced sneezes, other clinical symptoms, and the levels of histamine, tryptase, albumin, lysozyme, and cysteinyl-leukotrienes (third study only) in nasal lavage fluids. Results: Both concentrations of olopatadine produced significant inhibition of all nasal symptoms, compared with placebo. Olopatadine, 0. 1%, inhibited lysozyme levels, but olopatadine, 0.2%, inhibited histamine, albumin, and lysozyme. The effects of olopatadine, 0. 1%, were comparable to those of azelastine, 0. 1%. Conclusions: Olopatadine, at 0. 1% and 0.2% concentrations, was effective in suppressing allergen-induced nasal symptoms. At 0.2%, olopatadine provided evidence suggestive of inhibition of mast cell degranulation. C1 [Pipkorn, Patrik; Costantini, Candy; Reynolds, Curt; Sanico, Alvin; Togias, Alkis] Johns Hopkins Univ, Dept Med, Div Allergy & Clin Immunol, Baltimore, MD USA. [Wall, Michael; Drake, Margaret] Alcon Res Ltd, Ft Worth, TX USA. [Proud, David] Univ Calgary, Inst Infect Immun & Inflammat, Calgary, AB, Canada. [Proud, David] Univ Calgary, Dept Physiol & Biophys, Calgary, AB, Canada. [Togias, Alkis] Johns Hopkins Univ, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD USA. RP Togias, A (reprint author), NIAID, Div Allergy Immunol & Transplantat, Natl Inst Hlth, 6610 Rockledge Dr,Room 3065, Bethesda, MD 20892 USA. EM togiasa@niaid.nih.gov NR 54 TC 10 Z9 10 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD JUL PY 2008 VL 101 IS 1 BP 82 EP 89 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 325KY UT WOS:000257589000014 PM 18681089 ER PT J AU Nishi, N Sugiyama, H Hsu, WL Soda, M Kasagi, F Mabuchi, K Kodama, K AF Nishi, Nobuo Sugiyama, Hiromi Hsu, Wan-Ling Soda, Midori Kasagi, Fumiyoshi Mabuchi, Kiyohiko Kodama, Kazunori TI Differences in mortality and incidence for major sites of cancer by education level in a Japanese population SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE cancer; incidence; mortality; education; Japan ID ATOMIC-BOMB SURVIVORS; SOCIOECONOMIC-STATUS; METROPOLITAN-AREA; INCIDENCE RATES; DEATH AB PURPOSE: We aimed to examine the relationships between education and mortality and incidence for major sites of cancer in a Japanese population. METHODS: Subjects were 32,883 respondents of questionnaire survey in 1978 with ages younger than 75 years. Cancer cases were ascertained through 2001, and causes of deaths were identified through 2003. Hazard ratios of deaths from cancer or developing cancers were compared among those with 9 or less, 10-12, and 13 years or more of education using Cox proportional hazard models. RESULTS: As for cancer mortality of all sites combined, a statistically significantly decreasing trend was observed in age-adjusted models in both men and women, but no significant differences were observed in multivariate-adjusted (age, body mass index, smoking, radiation dose, and city) models. Among major cancer sites (stomach, colon/rectum, liver, lung, and female breast) examined, a significantly decreasing trend was observed for male liver cancer in a multivariate-adjusted model. As for incidence, a significantly decreasing trend was observed for cancer of all sites combined in men, and for male liver and prostate cancer and female lung cancer in a multivariate-adjusted model. CONCLUSIONS: Educational differences in cancer incidence and mortality were generally rather small, but were significant for incidence for male all-site, male liver, prostate, and female lung cancers. C1 [Nishi, Nobuo; Sugiyama, Hiromi; Kasagi, Fumiyoshi] Radiat Effects Res Fdn, Dept Epidemiol, Hiroshima Lab, Minami Ku, Hiroshima 7320815, Japan. [Hsu, Wan-Ling] Radiat Effects Res Fdn, Dept Stat, Hiroshima 7320815, Japan. [Soda, Midori] Radiat Effects Res Fdn, Dept Epidemiol, Nagasaki Lab, Hiroshima 7320815, Japan. [Mabuchi, Kiyohiko] Natl Canc Inst, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, Bethesda, MD USA. RP Nishi, N (reprint author), Radiat Effects Res Fdn, Dept Epidemiol, Hiroshima Lab, Minami Ku, 5-2 Hijiyama Pk, Hiroshima 7320815, Japan. EM nnishi@rerf.or.jp FU Intramural NIH HHS; NCI NIH HHS [N01CP31012, N01 CP031012] NR 30 TC 8 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 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JUL PY 2008 VL 18 IS 7 BP 584 EP 591 DI 10.1016/j.annepidem.2008.02.003 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 319FL UT WOS:000257149400010 PM 18486486 ER PT J AU Yan, LK Zheng, G Li, ZH AF Yan, Lihan K. Zheng, Gang Li, Zhaohai TI Two-stage group sequential robust tests in family-based association studies: Controlling type I error SO ANNALS OF HUMAN GENETICS LA English DT Article DE alpha spending function; family-based studies; genetic model; group sequential test; MAX; robust procedures ID CANDIDATE-GENE ASSOCIATION; ALPHA SPENDING FUNCTION; CLINICAL-TRIALS; LINKAGE TESTS; SAMPLE-SIZE; DESIGNS; POWER; DISEQUILIBRIUM; SUBDIVISION; BOUNDARIES AB In family-based association studies, an optimal test statistic with asymptotic normal distribution is available when the underlying genetic model is known (e.g., recessive, additive, multiplicative, or dominant). In practice, however, genetic models for many complex diseases are usually unknown. Using a single test statistic optimal for one genetic model may lose substantial power when the model is mis-specified. When a family of genetic models is scientifically plausible, the maximum of several tests, each optimal for a specific genetic model, is robust against the model mis-specification. This robust test is preferred over a single optimal test. Recently, cost-effective group sequential approaches have been introduced to genetic studies. The group sequential approach allows interim analyses and has been applied to many test statistics, but not to the maximum statistic. When the group sequential method is applied, type I error should be controlled. We propose and compare several approaches of controlling type I error rates when group sequential analysis is conducted with the maximum test for family-based candidate-gene association studies. For a two-stage group sequential robust procedure with a single interim analysis, two critical values for the maximum tests are provided based on a given alpha spending function to control the desired overall type I error. C1 [Yan, Lihan K.; Li, Zhaohai] George Washington Univ, Dept Stat, Biostat Program, Washington, DC 20052 USA. [Yan, Lihan K.] EMMES Corp, Rockville, MD USA. [Zheng, Gang] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. [Li, Zhaohai] NICHHD, Biometry & Math Stat Branch, Rockville, MD USA. RP Li, ZH (reprint author), George Washington Univ, Dept Stat, Biostat Program, Washington, DC 20052 USA. EM zli@gwu.edu FU NEI NIH HHS [EY014478] NR 31 TC 6 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD JUL PY 2008 VL 72 BP 557 EP 565 DI 10.1111/j.1469-1809.2008.00435.x PN 4 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 312QC UT WOS:000256684900011 PM 18325081 ER PT J AU Bainbridge, KE Hoffman, HJ Cowie, CC AF Bainbridge, Kathleen E. Hoffman, Howard J. Cowie, Catherine C. TI Diabetes and hearing impairment in the United States: Audiometric evidence from the National Health and Nutrition Examination Survey, 1999 to 2004 SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID OLDER-ADULTS; PRIMARY-CARE; INNER EAR; MELLITUS; EPIDEMIOLOGY; NOISE; ASSOCIATION; POPULATION; PREVALENCE; MANAGEMENT AB Background: Diabetes might affect the vasculature and neural system of the inner ear, leading to hearing impairment. Objective: To determine whether hearing impairment is more prevalent among U. S. adults with diabetes. Design: Cross-sectional analysis of nationally representative data. Setting: National Health and Nutrition Examination Survey, 1999 to 2004. Participants: 5140 noninstitutionalized adults age 20 to 69 years who had audiometric testing. Measurements: Hearing impairment was assessed from the pure tone average of thresholds over low or mid-frequencies (500, 1000, and 2000 Hz) and high frequencies (3000, 4000, 6000, and 8000 Hz) and was defined as mild or greater severity (pure tone average > 25 decibels hearing level [dB HL]) and moderate or greater severity (pure tone average > 40 dB HL). Results: Hearing impairment was more prevalent among adults with diabetes. Age-adjusted prevalence of low-or mid-frequency hearing impairment of mild or greater severity in the worse ear was 21.3% (95% CI, 15.0% to 27.5%) among 399 adults with diabetes compared with 9.4% (CI, 8.2% to 10.5%) among 4741 adults without diabetes. Similarly, age-adjusted prevalence of high-frequency hearing impairment of mild or greater severity in the worse ear was 54.1% (CI, 45.9% to 62.3%) among those with diabetes compared with 32.0% (CI, 30.5% to 33.5%) among those without diabetes. The association between diabetes and hearing impairment was independent of known risk factors for hearing impairment, such as noise exposure, ototoxic medication use, and smoking (adjusted odds ratios for low- or mid-frequency and high-frequency hearing impairment were 1.82 [CI, 1.27 to 2.60] and 2.16 [CI, 1.47 to 3.18], respectively). Limitations: The diagnosis of diabetes was based on self-report. The investigators could not distinguish between type 1 and type 2 diabetes. Noise exposure was based on participant recall. Conclusion: Hearing impairment is common in adults with diabetes, and diabetes seems to be an independent risk factor for the condition. C1 [Bainbridge, Kathleen E.] Social & Sci Syst, Silver Spring, MD 20910 USA. Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA. NIDDK, Bethesda, MD USA. RP Bainbridge, KE (reprint author), Social & Sci Syst, 8757 Georgia Ave,12th Floor, Silver Spring, MD 20910 USA. EM kbainbridge@s-3.com FU NIAAA NIH HHS [HHSN267200700001C]; NIDDK NIH HHS [GS1-0F-00381L, N001 DK12478]; NLM NIH HHS [HHSN267200700001G]; PHS HHS [GS1-0F-00381L, HHSN 26720070000 1G] NR 39 TC 130 Z9 143 U1 1 U2 8 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUL 1 PY 2008 VL 149 IS 1 BP 1 EP + PG 19 WC Medicine, General & Internal SC General & Internal Medicine GA 323EZ UT WOS:000257428200001 PM 18559825 ER PT J AU Giaccone, G Zucali, PA AF Giaccone, G. Zucali, P. A. TI Src as a potential therapeutic target in non-small-cell lung cancer SO ANNALS OF ONCOLOGY LA English DT Review DE non-small cell lung cancer; Src; targeted therapy; tyrosine kinase ID GROWTH-FACTOR RECEPTOR; CHRONIC MYELOID-LEUKEMIA; TYROSINE KINASE INHIBITOR; C-SRC; CYTOGENETIC RESPONSES; ADENOCARCINOMA CELLS; FAMILY KINASES; IMATINIB-RESISTANT; BREAST-CANCER; HUMAN TUMORS AB Lung cancer is the most common cause of cancer-related death, with non-small-cell lung cancer (NSCLC) accounting for 80%-85% of all cases. Although survival rates are reasonably good for patients diagnosed with very early disease, the majority of patients present with advanced disease. For these patients, palliation and improvements in quality of life are the primary goals of therapy. Although chemotherapeutic agents remain the cornerstone of first-line therapy, these agents have limited use in patients who have relapsed and have metastatic disease. Therefore, new strategies are required to improve survival and quality of life in this setting. With the substantial advances in our understanding of tumour biology, it has been possible to identify signalling pathways involved in mediating tumour growth and progression. These pathways offer targets for new biological agents such as small molecule inhibitors and monoclonal antibodies. One such target is Src, a tyrosine kinase that is involved in multiple aspects of tumorigenesis including proliferation, migration and angiogenesis. Increased levels of Src expression have been found in a range of cancers, especially breast, colorectal, prostate and lung. Preliminary preclinical data and pharmacodynamic data suggest that Src inhibition is a viable therapeutic option in the treatment of advanced NSCLC. C1 [Giaccone, G.] Natl Canc Inst, Ctr Canc Res, Bethesda, MD 20892 USA. [Zucali, P. A.] Ist Clin Humanitas, Dipartimento Oncol Ematol, Rozzano, Italy. RP Giaccone, G (reprint author), Natl Canc Inst, Ctr Canc Res, 10 Ctr Dr,Bldg 10,Room 12N226, Bethesda, MD 20892 USA. EM giacconeg@mail.nih.gov RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 NR 50 TC 39 Z9 40 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUL PY 2008 VL 19 IS 7 BP 1219 EP 1223 DI 10.1093/annonc/mdn048 PG 5 WC Oncology SC Oncology GA 319NB UT WOS:000257169300003 PM 18388349 ER PT J AU Henry, LR Solomon, NP Howard, R Gurevich-Uvena, J Horst, LB Coppit, G Orlikoff, R Libutti, SK Shaha, AR Stojadinovic, A AF Henry, Leonard R. Solomon, Nancy Pearl Howard, Robin Gurevich-Uvena, Joyce Horst, Leah B. Coppit, George Orlikoff, Robert Libutti, Steven K. Shaha, Ashok R. Stojadinovic, Alexander TI The functional impact on voice of sternothyroid muscle division during thyroidectomy SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE sternothyroid; voice; thyroidectomy ID SUPERIOR LARYNGEAL NERVE; EXTERNAL BRANCH; SURGERY; IDENTIFICATION; DISEASE; INJURY AB Background: Post-thyroidectomy voice dysfunction may occur in the absence of laryngeal nerve injury. Strap muscle division has been hypothesized as one potential contributor to dysphonia. Methods: Vocal-function data, prospectively recorded before and after thyroidectomy from two high-volume referral institutions, were utilized. Patient-reported symptoms, laryngoscopic, acoustic, and aerodynamic parameters were recorded at 2 weeks and 3 months postoperatively. Patients with and without sternothyroid muscle division during surgery were compared for voice changes. Patients with laryngeal nerve injury, sternohyoid muscle division, arytenoid subluxation or no early postoperative follow-up evaluation were excluded. Differences between study groups and outcomes were compared using t-tests and rank-sum tests as appropriate. Results: Of 84 patients included, 45 had sternothyroid division. Distribution of age, gender, extent of thyroidectomy, specimen size, and laryngeal nerve identification rates did not differ significantly between groups. There was a significant predilection for or against sternothyroid muscle division according to medical center. No significant difference in reported voice symptoms was observed between groups 2 weeks or 3 months after thyroidectomy. Likewise, acoustic and aerodynamic parameters did not differ significantly between groups at these postoperative study time points. Conclusion: Sternothyroid muscle division is occasionally employed during thyroidectomy to gain superior pedicle exposure. Division of this muscle does not appear to be associated with adverse functional voice outcome, and should be utilized at surgeon discretion during thyroidectomy. C1 [Stojadinovic, Alexander] Walter Reed Army Med Ctr, Dept Surg, Div Surg Oncol, Washington, DC 20307 USA. [Stojadinovic, Alexander] USA, Mil Canc Inst, Washington, DC 20307 USA. [Henry, Leonard R.] USN, Med Ctr, Dept Surg, Div Surg Oncol, Bethesda, MD 20889 USA. [Solomon, Nancy Pearl; Gurevich-Uvena, Joyce] Walter Reed Army Med Ctr, Dept Surg, Army Audiol & Speech Ctr, Washington, DC 20307 USA. [Howard, Robin] Walter Reed Army Med Ctr, Dept Clin Invest, Div Biostat, Washington, DC 20307 USA. [Horst, Leah B.] Walter Reed Army Med Ctr, Dept Surg, Div Anesthesia, Washington, DC 20307 USA. [Coppit, George] Walter Reed Army Med Ctr, Dept Surg, Div Otolaryngol Head & Neck Surg, Washington, DC 20307 USA. [Orlikoff, Robert] Seton Hall Univ, Dept Speech Language Pathol, S Orange, NJ 07079 USA. [Libutti, Steven K.] Natl Canc Inst, Surg Branch, Bethesda, MD 20889 USA. [Shaha, Ashok R.] Mem Sloan Kettering Canc Ctr, Dept Surg Oncol, Head & Neck Serv, New York, NY 10021 USA. RP Stojadinovic, A (reprint author), Walter Reed Army Med Ctr, Dept Surg, Div Surg Oncol, 6900 Georgia Ave, Washington, DC 20307 USA. EM Alexander.stojadinovic@na.amedd.army.mil OI Orlikoff, Robert/0000-0003-0048-6541 NR 24 TC 25 Z9 25 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JUL PY 2008 VL 15 IS 7 BP 2027 EP 2033 DI 10.1245/s10434-008-9936-8 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA 320GY UT WOS:000257222900029 PM 18459003 ER PT J AU Zhang, B Zhang, X Tang, FL Zhu, LP Liu, Y Lipsky, PE AF Zhang, B. Zhang, X. Tang, F. L. Zhu, L. P. Liu, Y. Lipsky, P. E. TI Clinical significance of increased CD4(+)CD25(-)Foxp3(+) T cells in patients with new-onset systemic lupus erythematosus SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID FOXP3; EXPRESSION; CD127 AB Objective: To investigate the expressions of Foxp3 and CD25 on CD4(+) T cells from patients with new-onset systemic lupus erythematosus (SLE) and assess their clinical significance. Methods: 10 patients with active (systemic lupus erythematosus Disease Activity Index (SLEDAI) >= 10) and 11 with inactive (SLEDAI <= 5) new-onset SLE as well as 11 healthy volunteers were enrolled. The expressions of CD25, Foxp3 and CD127 on CD4(+) T cells were analysed by flow cytometry. Proliferation assays were performed on isolated CD4(+)CD25(+) or CD4(+)CD25-T cells, or both. Results: There was no significant difference in the number of CD4(+)CD25(+)Foxp3(+) T cells in subjects with either active or inactive SLE compared with normal controls (p>0.05). Moreover, the suppressive capacity of CD4(+)CD25(+) T cells in patients with new-onset lupus was not impaired as measured by the ability to inhibit proliferation of CD4(+)CD25-T cells. Interestingly, CD4(+)CD25(-)Foxp3(+) T cells in new-onset lupus (2.97-10.94%) were significantly more frequent than in normal controls (1.01-3.62%) (p< 0.01), and correlated positively with the titres of anti-dsDNA antibodies (p= 0.029). Few of these cells expressed CD127. Treatment with glucocorticoids and cyclophosphamide reduced CD4(+)CD25(-)Foxp3(+) T cells in 8 of 10 patients with active disease. Conclusions: There was a significant increase in CD4(+)CD25(-)Foxp3(+) T cells in patients with new-onset SLE that correlated with anti-dsDNA titres, whereas no alteration in either the percentage or function of CD4(+)CD25(+)Foxp3(+) T cells was observed. C1 [Zhang, B.; Zhang, X.; Tang, F. L.] Chinese Acad Med Sci, Dept Rheumatol, Peking Union Med Coll Hosp, Beijing 100730, Peoples R China. [Zhang, B.; Zhang, X.; Tang, F. L.; Zhu, L. P.; Liu, Y.] Peking Union Med Coll, Beijing 100021, Peoples R China. [Zhu, L. P.; Liu, Y.] Chinese Acad Med Sci, Dept Immunol, Inst Basic Med Sci, Beijing 100730, Peoples R China. [Lipsky, P. E.] NIAMS, Autoimmun Branch, NIH, Bethesda, MD USA. RP Zhang, X (reprint author), Chinese Acad Med Sci, Dept Rheumatol, Peking Union Med Coll Hosp, 1 Shuaifuyuan, Beijing 100730, Peoples R China. EM zxpumch2003@yahoo.com.cn OI zhang, xuan/0000-0001-8775-1699 NR 14 TC 62 Z9 71 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2008 VL 67 IS 7 BP 1037 EP 1040 DI 10.1136/ard.2007.083543 PG 4 WC Rheumatology SC Rheumatology GA 312TV UT WOS:000256694600024 PM 18199598 ER PT J AU Liu, Y Lan, Q Shen, M Jin, J Mumford, J Ren, DX Keohavong, P AF Liu, Yang Lan, Qing Shen, Min Jin, Jide Mumford, Judy Ren, Dianxu Keohavong, Phouthone TI Aberrant gene promoter methylation in sputum from individuals exposed to smoky coal emissions SO ANTICANCER RESEARCH LA English DT Article DE promoter methylation; smoke; coal; PAH; benzopyrene; sputum; lung cancer ID LUNG-CANCER MORTALITY; K-RAS MUTATIONS; XUAN-WEI; INDOOR COAL; CHEMICAL CHARACTERIZATION; COMBUSTION EMISSIONS; MULTIPLE GENES; NEVER-SMOKERS; HYPERMETHYLATION; CHINA AB Background: Recent studies suggested the potential for aberrant gene promoter methylation in sputum as a predictive marker for lung cancer. Here, the promoter methylation of p16, MGMT, RASSF1A and DAPK genes was investigated in sputum of individuals exposed to smoky coal emissions in Xuan Wei, China, where the lung cancer rate is more than 6 times the Chinese national average. Materials and Methods: Sputum DNA of 107 noncancer individuals and 58 lung cancer patients was screened for promoter methylation using methylation-specific PCR. Results: Promoter methylation of the p16 gene was detected in about half [51.4% (551107)] of sputum DNA from noncancer individuals, a frequency higher than that observed for the RASSF1A (29.9%), MGMT (17.8%) and DAPK (15.9%) genes. Furthermore, the p16 gene was affected by promoter methylation at a frequency even higher among the lung cancer group, compared with the noncancer group [70.7% (41/58) versus 51.7% (55/107), p=0.017]. Conclusion: Individuals exposed to smoky coal emissions in this region harbored frequent promoter methylation of these genes in. their sputum and some of such alterations may be involved in lung tumor development. C1 [Liu, Yang; Jin, Jide; Keohavong, Phouthone] Univ Pittsburgh, Dept Environm & Occupat Hlth, Pittsburgh, PA 15219 USA. [Lan, Qing; Shen, Min] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Mumford, Judy] US EPA, Natl Hlth & Environm Effects Lab, Res Triangle Pk, NC 27711 USA. [Ren, Dianxu] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. [Ren, Dianxu] Univ Pittsburgh, Ctr Res & Evaluat, Sch Nursing, Pittsburgh, PA 15261 USA. [Keohavong, Phouthone] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA. RP Liu, Y (reprint author), Univ Pittsburgh, Dept Environm & Occupat Hlth, 100 Technol Dr, Pittsburgh, PA 15219 USA. EM pho1@pitt.edu OI Keohavong, Phouthone/0000-0001-7812-4925 FU Intramural NIH HHS [ZIA CP010121-14] NR 40 TC 13 Z9 14 U1 1 U2 2 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JUL-AUG PY 2008 VL 28 IS 4B BP 2061 EP 2066 PG 6 WC Oncology SC Oncology GA 333KK UT WOS:000258151200008 PM 18751376 ER PT J AU Lisk, G Pain, M Gluman, IY Kambhampati, S Furuya, T Su, XZ Fay, MP Goldberg, DE Desai, SA AF Lisk, Godfrey Pain, Margaret Gluman, Ilya Y. Kambhampati, Shivkumar Furuya, Tetsuya Su, Xin-zhuan Fay, Michael P. Goldberg, Daniel E. Desai, Sanjay A. TI Changes in the plasmodial surface anion channel reduce leupeptin uptake and can confer drug resistance in Plasmodium falciparum-infected erythrocytes SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID MALARIA PARASITE; CYSTEINE PROTEINASE; CHLOROQUINE RESISTANCE; PROTEASE INHIBITOR; ANTIMALARIAL DRUG; HOST ERYTHROCYTE; MUTATIONS; AMPLIFICATION; PYRIMETHAMINE; MEROZOITES AB Cysteine protease inhibitors kill malaria parasites and are being pursued for development as antimalarial agents. Because they have multiple targets within bloodstream-stage parasites, workers have assumed that resistance to these inhibitors would not be acquired easily. In the present study, we used in vitro selection to generate a parasite resistant to growth inhibition by leupeptin, a broad-profile cysteine and serine protease inhibitor. Resistance was not associated with upregulation of cysteine protease activity, reduced leupeptin sensitivity of this activity, or expression level changes for putative cysteine or serine proteases in the parasite genome. Instead, it was associated with marked changes in the plasmodial surface anion channel (PSAC), an ion channel on infected erythrocytes that functions in nutrient and bulky organic solute uptake. Osmotic fragility measurements, electrophysiological recordings, and leupeptin uptake studies revealed selective reductions in organic solute permeability via PSAC, altered single-channel gating, and reduced inhibitor affinity. These changes yielded significantly reduced leupeptin uptake and could fully account for the acquired resistance. PSAC represents a novel route for the uptake of bulky hydrophilic compounds acting against intraerythrocytic parasite targets. Drug development based on such compounds should proceed cautiously in light of possible resistance development though the selection of PSAC mutants. C1 [Lisk, Godfrey; Pain, Margaret; Kambhampati, Shivkumar; Furuya, Tetsuya; Su, Xin-zhuan; Desai, Sanjay A.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Fay, Michael P.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. [Gluman, Ilya Y.; Goldberg, Daniel E.] Washington Univ, Dept Mol Microbiol, Howard Hughes Med Inst, St Louis, MO 63110 USA. [Gluman, Ilya Y.; Goldberg, Daniel E.] Washington Univ, Dept Med, St Louis, MO USA. RP Desai, SA (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Room 3W-01,12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM sdesai@niaid.nih.gov RI Desai, Sanjay/B-7110-2009; Furuya, Tetsuya/J-5916-2013; Furuya, Tetsuya/H-2412-2013; OI Furuya, Tetsuya/0000-0003-3979-7072; Fay, Michael P./0000-0002-8643-9625; Su, Xinzhuan/0000-0003-3246-3248 FU Intramural NIH HHS; NIAID NIH HHS [AI-47798, R01 AI047798] NR 39 TC 26 Z9 26 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUL PY 2008 VL 52 IS 7 BP 2346 EP 2354 DI 10.1128/AAC.00057-08 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 319SE UT WOS:000257183400008 PM 18443109 ER PT J AU Horak, CE Lee, JH Marshall, JC Shreeve, SM Steeg, PS AF Horak, Christine E. Lee, Jong Heun Marshall, Jean-Claude Shreeve, S. Martin Steeg, Patricia S. TI The role of metastasis, suppressor genes in metastatic dormancy SO APMIS LA English DT Review DE dormancy; KAII; KISSI; metastasis; metastasis supressor gene; MKK4; MKK7; Nm23 ID SQUAMOUS-CELL CARCINOMA; HUMAN OVARIAN-CARCINOMA; INHIBITOR PROTEIN EXPRESSION; PROSTATE-CANCER METASTASIS; GREEN FLUORESCENT PROTEIN; SIGNAL-REGULATED KINASE; TISSUE GROWTH-FACTOR; HUMAN-MELANOMA CELLS; ACID RECEPTOR EDG2; BREAST-CANCER AB Metastasis suppressor genes (MSGs) are defines by their ability to inhibit overt metastasis in a secondary organ without affecting tumor growth at the primary site. Over 20 MSGs have been confirmes in vivo. This class of genes is only unified by their capacity to supress metastasis, as they encode for proteins with a wide range of biochemical activities that are components of a varity of signaling pathways. In addition, metastasis supressors impinge upon different stages of the metastatic cascade to manifest their supressive effects. The MSGs KISSI, KAII, MK K4/7 and Nm23-HI promote tumor dormancy at the metastatic site, since tumor cells with induced expression of these MSGs disseminate, but do not form overt metastases in the secondary organ throughout the duration of a metastasis assay. Evidence suggests of solitary cells at the secondary site. KAII induces growth arrest prior to extravasation by binding a vascular endothelial cell surface marker. MK K4, MKK7 and Nm23-HI appear to promote dormancy of micrometastatic colonies, after disseminated tumor cells have undergone several rounds of proliferation. Other MSGs may also function in tumor dormancy, but so far their role has not been fully elucidated. Therapeutic approaches that either mimic the effects of MSGs or re-establish MSg expression in metastatic lesions may hold promise fo the establishment or maintenance of dormancy. C1 [Horak, Christine E.; Lee, Jong Heun; Marshall, Jean-Claude; Shreeve, S. Martin; Steeg, Patricia S.] NCI, Ctr Canc Res, Mol Pharmacol Lab, Womens Canc Sect, Bethesda, MD 20892 USA. RP Horak, CE (reprint author), NCI, Ctr Canc Res, Mol Pharmacol Lab, Womens Canc Sect, 37 Convent Dr, Bethesda, MD 20892 USA. EM horake@mail.nih.gov FU Intramural NIH HHS [ZIA SC000892-26] NR 106 TC 54 Z9 55 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0903-4641 J9 APMIS JI APMIS PD JUL-AUG PY 2008 VL 116 IS 7-8 BP 586 EP 601 DI 10.1111/j.1600-0463.2008.01027.x PG 16 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA 345ZG UT WOS:000259037600006 PM 18834404 ER PT J AU Tanofsky-Kraff, M Ranzenhofer, LM Yanovski, SZ Schvey, NA Faith, M Gustafson, J Yanovski, JA AF Tanofsky-Kraff, Marian Ranzenhofer, Lisa M. Yanovski, Susan Z. Schvey, Natasha A. Faith, Myles Gustafson, Jennifer Yanovski, Jack A. TI Psychometric properties of a new questionnaire to assess eating in the absence of hunger in children and adolescents SO APPETITE LA English DT Article; Proceedings Paper CT International Conference on Eating Disorders of the Academy-for-Eating-Disorders CY MAY 02-05, 2007 CL Baltimore, MD SP Acad Eating Disorders DE eating in the absence of hunger; obesity; overweight; emotional and external eating; children and adolescents ID OVERWEIGHT CHILDREN; BEHAVIOR QUESTIONNAIRE; DISORDER EXAMINATION; PUBERTAL CHANGES; UNITED-STATES; GIRLS; OBESITY; SCALE; PSYCHOPATHOLOGY; PREVALENCE AB Background: Eating in the absence of hunger (EAH), studied in the context of laboratory paradigms, has been associated with obesity and is predictive of excess weight gain in children. However, no easily administered questionnaire exists to assess for EAH in children. Objective: We developed an Eating in the Absence of Hunger Questionnaire to be administered to children and adolescents (EAH-C) and examined psychometric properties of the measure. Design: Two-hundred and twenty-six obese (BMI >= 95th percentile for age and sex, n = 73) and non-obese (BMI < 95th percentile, n = 153) youth (mean age +/- S.D., 14.4 +/- 2.5 y) completed the EAH-C and measures of loss of control and emotional eating, and general psychopathology. Temporal stability was assessed in a subset of participants. Results: Factor analysis generated three subscales for the EAH-C: Negative Affect, External Eating, and Fatigue/Boredom. Internal consistency for all subscales was established (Cronbach's alphas: 0.80-0.88). The EAH-C subscales had good convergent validity with emotional eating and loss of control episodes (p's < 0.01). Obese children reported higher Negative Affect subscale scores than non-obese children (p <= 0.05). All three subscales were positively correlated with measures of general psychopathology. Intra-class correlation coefficients revealed temporal stability for all subscales (ranging from 0.65 to 0.70, p's < 0.01). We conclude that the EAH-C had internally consistent subscales with good convergent validity and temporal stability, but may have limited discriminant validity. Further investigations examining the EAH-C in relation to laboratory feeding studies are required to determine whether reported EAH is related to actual energy intake or to the development of excess weight gain. Published by Elsevier Ltd. C1 [Tanofsky-Kraff, Marian; Ranzenhofer, Lisa M.; Yanovski, Susan Z.; Schvey, Natasha A.; Gustafson, Jennifer; Yanovski, Jack A.] NICHD, Program Dev Endocrinol & Genet, DHHS, NIH,Hatfield Clin Res Ctr, Bethesda, MD 20892 USA. [Tanofsky-Kraff, Marian; Ranzenhofer, Lisa M.; Schvey, Natasha A.] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA. [Yanovski, Susan Z.] NIDDK, Div Digest Dis & Nutr, NIH, DHHS, Bethesda, MD 20892 USA. [Faith, Myles] Univ Penn, Sch Med, Ctr Weight & Eating Disorders, Philadelphia, PA 19104 USA. RP Tanofsky-Kraff, M (reprint author), NICHD, Program Dev Endocrinol & Genet, DHHS, NIH,Hatfield Clin Res Ctr, Room 1-3330, Bethesda, MD 20892 USA. EM mtanofsky@usuhs.edu OI Yanovski, Jack/0000-0001-8542-1637 FU Intramural NIH HHS [Z99 HD999999, Z01 HD000641-12]; NICHD NIH HHS [HD042169, R01 HD042169, R01 HD042169-01A1, Z01 HD000641] NR 41 TC 47 Z9 49 U1 1 U2 16 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0195-6663 J9 APPETITE JI Appetite PD JUL PY 2008 VL 51 IS 1 BP 148 EP 155 DI 10.1016/j.appet.2008.01.001 PG 8 WC Behavioral Sciences; Nutrition & Dietetics SC Behavioral Sciences; Nutrition & Dietetics GA 306DE UT WOS:000256227700023 PM 18342988 ER PT J AU Gungor, D AF Gungor, Derya TI The meaning of parental control in migrant, sending, and host communities: Adaptation or persistence? SO APPLIED PSYCHOLOGY-AN INTERNATIONAL REVIEW-PSYCHOLOGIE APPLIQUEE-REVUE INTERNATIONALE LA English DT Article ID INTERGENERATIONAL TRANSMISSION; ACADEMIC-ACHIEVEMENT; NEGLECTFUL FAMILIES; UNITED-STATES; SELF-ESTEEM; ADOLESCENTS; ACCULTURATION; AMERICAN; AUTHORITARIAN; ADJUSTMENT AB The goal of the present study was to investigate whether migrant adolescents tend to adopt the host culture's view of parental control or whether they are inclined to reaffirm their heritage culture with regard to the meaning assigned to parental control. The hypotheses regarding the level and meaning of parental control were tested on 296 Turkish-Belgian adolescents, 306 Turks in Turkey, and 304 Belgians in Belgium with median ages of 16, 17, and 16, respectively. Although migrants reported the highest level of parental control, their ratings of parental warmth, satisfaction with the relationships with their parents, and self-esteem did not correlate with parental control as was the case among Belgians. The findings suggest that traditional parenting is accentuated in migrant families, and that there is continuity in the traditional meaning of parental control in migration. Findings are discussed with reference to contextual factors that may reinforce culture maintenance in migration. C1 [Gungor, Derya] NICHHD, Child & Family Res Sect, Bethesda, MD 20892 USA. [Gungor, Derya] Univ Utrecht, NL-3508 TC Utrecht, Netherlands. RP Gungor, D (reprint author), NICHHD, Child & Family Res Sect, 6705 Rockledge Dr,Suite 8030, Bethesda, MD 20892 USA. NR 61 TC 12 Z9 12 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-994X J9 APPL PSYCHOL-INT REV JI Appl. Psychol.-Int. Rev.-Psychol. Appl.-Rev. Int. PD JUL PY 2008 VL 57 IS 3 BP 397 EP 416 DI 10.1111/j.1464-0597.2007.00323.x PG 20 WC Psychology, Applied SC Psychology GA 309DX UT WOS:000256442000003 ER PT J AU McDonald, CB Seldeen, KL Deegan, BJ Lewis, MS Farooq, A AF McDonald, Caleb B. Seldeen, Kenneth L. Deegan, Brian J. Lewis, Marc S. Farooq, Amjad TI Grb2 adaptor undergoes conformational change upon dimerization SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE Grb2 dimerization; isothermal titration calorimetry; analytical ultra-centrifugation; size-exclusion chromatography; mass spectrometry ID RECEPTOR TYROSINE KINASES; SH3 DOMAIN; TRANSLATIONAL ENTROPY; SIGNALING PATHWAY; CRYSTAL-STRUCTURE; MOLECULAR-BASIS; HIGH-AFFINITY; C-CBL; RAS; BINDING AB Grb2 is an adaptor protein that couples activated receptor tyrosine kinases to downstream effector molecules such as Ras and Akt. Despite being a central player in mitogenic signaling and a target for therapeutic intervention, the role of Grb2 oligomerization in cellular signaling is not well understood. Here, using the techniques of size-exclusion chromatography, mass spectrometry, analytical ultra-centrifugation and isothermal titration calorimetry, we demonstrate that Grb2 exists in monomer-dimer equilibrium in solution and that the dissociation of dimer into monomers is entropically-driven without an unfavorable enthalpic change at physiological temperatures. Our data indicate that enthalpy and entropy of dimer dissociation are highly temperature-dependent and largely compensate each other resulting in negligible effect of temperature on the overall free energy. From the plot of enthalpy change versus temperature, the magnitude of heat capacity change derived is much smaller than that expected from the rather large molecular surfaces becoming solvent-occluded upon Grb2 dimerization, implying that Grb2 monomers undergo conformational rearrangement upon dimerization. 3D structural models of Grb2 dimer and monomers suggest strongly that such conformational rearrangement upon dimerization may arise from domain swapping. Taken together, our study provides novel insights into the role of Grb2 as an adaptor in cellular signaling circuitry and how Grb2 dimerization may impart high fidelity in signal transduction as well as lead to rapid signal amplification upon receptor stimulation. (C) 2008 Elsevier Inc. All rights reserved. C1 [McDonald, Caleb B.; Seldeen, Kenneth L.; Deegan, Brian J.; Farooq, Amjad] Univ Miami, Leonard Miller Sch Med, Dept Biochem & Mol Biol, Miami, FL 33136 USA. [McDonald, Caleb B.; Seldeen, Kenneth L.; Deegan, Brian J.; Farooq, Amjad] Univ Miami, Leonard Miller Sch Med, UM Sylvester Braman Family Breast Canc Inst, Miami, FL 33136 USA. [Lewis, Marc S.] Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA. RP Farooq, A (reprint author), Univ Miami, Leonard Miller Sch Med, Dept Biochem & Mol Biol, Gautier Bldg,Room 214,1011 NW 15th St, Miami, FL 33136 USA. EM amjad@farooqlab.net RI Farooq, Amjad/B-5084-2012 NR 54 TC 16 Z9 16 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUL 1 PY 2008 VL 475 IS 1 BP 25 EP 35 DI 10.1016/j.abb.2008.04.008 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 318NT UT WOS:000257099500005 PM 18442468 ER PT J AU Zandi, PP Belmonte, PL Willour, VL Goes, FS Badner, JA Simpson, SG Gershon, ES McMahon, FJ DePaulo, JR Potash, JB AF Zandi, Peter P. Belmonte, Pamela L. Willour, Virginia L. Goes, Fernando S. Badner, Judith A. Simpson, Sylvia G. Gershon, Elliot S. McMahon, Francis J. DePaulo, J. Raymond, Jr. Potash, James B. CA Bipolar Disorder Phenome Grp Natl Inst Mental Hlth Geneticst TI Association study of wnt signaling pathway genes in bipolar disorder SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID GENOME SCAN METAANALYSIS; FAMILY-BASED TESTS; SYNTHASE KINASE-3; DYSBINDIN GENE; FZD3 GENE; SCHIZOPHRENIA; LINKAGE; LITHIUM; DIFFERENTIATION; SUSCEPTIBILITY AB Context: The Wnt signaling pathways promote cell growth and are best known for their role in embryogenesis and cancer. Several lines of evidence suggest that these pathways might also be involved in bipolar disorder. Objective: To test for an association between candidate genes in the Wnt signaling pathways and disease susceptibility in a family-based bipolar disorder study. Design: Two hundred twenty-seven tagging single-nucleotide polymorphisms (SNPs) from 34 genes were successfully genotyped. Initial results led us to focus on the gene PPARD, in which we genotyped an additional 13 SNPs for follow-up. Setting: Nine academic medical centers in the United States. Participants: Five hundred fifty-four offspring with bipolar disorder and their parents from 317 families. Main Outcome Measures: Family-based association using FBAT and HBAT (http://www.biostat.harvard.edu/similar to fbat/default.html; Harvard School of Public Health, Boston, Massachusetts). Exploratory analyses testing for interactions of PPARD SNPs with clinical covariates and with other Wnt genes were conducted with GENASSOC (Stata Corp, College Station, Texas). Results: In the initial analysis, the most significantly associated SNP was rs2267665 in PPARD (nominal P<.001). This remained significant at P=.05 by permutation after accounting for all SNPs tested. Additional genotyping in PPARD yielded 4 SNPs in 1 haplotype block that were significantly associated with bipolar disorder (P<.01), the most significant being rs9462082 (P<.001). Exploratory analyses revealed significant evidence (P<.01) for interactions of rs9462082 with poor functioning on the Global Assessment Scale (odds ratio [OR], 3.36; 95% confidence interval [CI], 1.85-6.08) and with SNPs in WNT2B (rs3790606: OR, 2.56; 95% CI, 1.67-4.00) and WNT7A (rs4685048: OR, 1.79; 95% CI, 1.23-2.63). Conclusions: We found evidence for association of bipolar disorder with PPARD, a gene in the Wnt signaling pathway. The consistency of this result with one from the Wellcome Trust Case-Control Consortium encourages further study. If the finding can be confirmed in additional samples, it may illuminate a new avenue for understanding the pathogenesis of severe bipolar disorder and developing more effective treatments. C1 [Zandi, Peter P.] Johns Hopkins Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. [Belmonte, Pamela L.; Willour, Virginia L.; Goes, Fernando S.; DePaulo, J. Raymond, Jr.; Potash, James B.] Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD USA. [Badner, Judith A.; Gershon, Elliot S.] Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. [Simpson, Sylvia G.] Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. [McMahon, Francis J.] NIMH, Genet Basis Mood & Anxiety Disorders Unit, Mood & Anxiety Program, NIH,US Dept HHS, Bethesda, MD 20892 USA. RP Zandi, PP (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Hampton House,Room 857,624 N Broadway, Baltimore, MD 21205 USA. EM pzandi@jhsph.edu OI Nurnberger, John/0000-0002-7674-1767; McMahon, Francis/0000-0002-9469-305X FU Intramural NIH HHS; NIMH NIH HHS [R01 MH059548, K01 MH-072866, K01 MH072866, K01 MH072866-01, R01 MH-042243, R01 MH-061613, R01 MH042243, R01 MH059533, R01 MH059534, R01 MH059535, R01 MH059545, R01 MH059553, R01 MH059556, R01 MH059567, R01 MH060068, R01 MH061613, Z01 MH002810] NR 43 TC 40 Z9 40 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUL PY 2008 VL 65 IS 7 BP 785 EP 793 DI 10.1001/archpsyc.65.7.785 PG 9 WC Psychiatry SC Psychiatry GA 323HS UT WOS:000257437800005 PM 18606951 ER PT J AU Vesga-Lopez, O Blanco, C Keyes, K Olfson, M Grant, BF Hasin, DS AF Vesga-Lopez, Oriana Blanco, Carlos Keyes, Katherine Olfson, Mark Grant, Bridget F. Hasin, Deborah S. TI Psychiatric disorders in pregnant and postpartum women in the United States SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID NATIONAL EPIDEMIOLOGIC SURVEY; ALCOHOL-USE-DISORDER; COMORBIDITY SURVEY REPLICATION; MATERNAL ANTENATAL ANXIETY; INTERVIEW SCHEDULE AUDADIS; GENERAL-POPULATION SAMPLE; MAJOR DEPRESSIVE DISORDER; SUBSTANCE USE DISORDERS; DSM-IV ALCOHOL; POSTNATAL DEPRESSION AB Context: Psychiatric disorders and substance use during pregnancy are associated with adverse outcomes for mothers and their offspring. Information about the epidemiology of these conditions in this population is lacking. Objective: To examine sociodemographic correlates, rates of DSM-IV Axis I psychiatric disorders, substance use, and treatment seeking among past-year pregnant and postpartum women in the United States. Design: National survey. Setting: Face-to-face interviews conducted in the 20012002 National Epidemiologic Survey on Alcohol and Related Conditions. Participants: A total of 43 093 respondents were interviewed, of whom 14 549 were women 18 to 50 years old with known past-year pregnancy status. Main Outcome Measures: Prevalence of 12-month DSM-IV Axis I psychiatric disorders, substance use, and treatment seeking. Results: Past-year pregnant and postpartum women had significantly lower rates of alcohol use disorders and any substance use, except illicit drug use, than nonpregnant women. In addition, currently pregnant women had a lower risk of having any mood disorder than nonpregnant women. The only exception was the significantly higher prevalence of major depressive disorder in postpartum than in nonpregnant women. Age, marital status, health status, stressful life events, and history of traumatic experiences were all significantly associated with higher risk of psychiatric disorders in pregnant and postpartum women. Lifetime and past-year treatment-seeking rates for any psychiatric disorder were significantly lower among past-year pregnant than nonpregnant women with psychiatric disorders. Most women with a current psychiatric disorder did not receive any mental health care in the 12 months prior to the survey regardless of pregnancy status. Conclusions: Pregnancy per se is not associated with increased risk of the most prevalent mental disorders, although the risk of major depressive disorder may be increased during the postpartum period. Groups of pregnant women with particularly high prevalence of psychiatric disorders were identified. Low rates of maternal mental health care underscore the need to improve recognition and delivery of treatment for mental disorders occurring during pregnancy and the postpartum period. C1 [Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA. [Vesga-Lopez, Oriana; Blanco, Carlos; Olfson, Mark] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Blanco, Carlos; Olfson, Mark] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. [Keyes, Katherine; Hasin, Deborah S.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA. RP Grant, BF (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Room 3077,MS 9304,5635 Fishers Ln, Bethesda, MD 20892 USA. EM bgrant@willco.niaaa.nih.gov RI Blanco, Carlos/I-4906-2013 OI Blanco, Carlos/0000-0001-6187-3057 FU Intramural NIH HHS [Z01 AA000449-04, Z99 AA999999]; NIAAA NIH HHS [K05 AA014223]; NIDA NIH HHS [DA019606, DA020783, DA023200, K02 DA023200, R01 DA019606, R01 DA020783]; NIMH NIH HHS [MH076051, R01 MH076051]; NIMHD NIH HHS [P60 MD000206] NR 89 TC 277 Z9 288 U1 8 U2 41 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUL PY 2008 VL 65 IS 7 BP 805 EP 815 DI 10.1001/archpsyc.65.7.805 PG 11 WC Psychiatry SC Psychiatry GA 323HS UT WOS:000257437800007 PM 18606953 ER PT J AU Washington, MK Berlin, J Branton, PA Burgart, LJ Carter, DK Fitzgibbons, PL Frankel, WL Jessup, JM Kakar, S Minsky, B Nakhleh, RE Compton, CC AF Washington, Mary Kay Berlin, Jordan Branton, Philip A. Burgart, Lawrence J. Carter, David K. Fitzgibbons, Patrick L. Frankel, Wendy L. Jessup, John M. Kakar, Sanjay Minsky, Bruce Nakhleh, Raouf E. Compton, Carolyn C. CA Canc Comm TI Protocol for the examination of specimens from patients with primary carcinomas of the colon and rectum SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; TOTAL MESORECTAL EXCISION; RING CELL-CARCINOMA; MICROSATELLITE INSTABILITY; LYMPH-NODES; RESECTION SPECIMENS; CURATIVE RESECTION; PROGNOSTIC-FACTORS; MINIMUM NUMBER; SURVIVAL C1 [Washington, Mary Kay] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. [Berlin, Jordan] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA. [Branton, Philip A.] Inova Fairfax Hosp, Dept Pathol, Falls Church, VA USA. [Burgart, Lawrence J.] Abbott NW Hosp, Allina Labs, Minneapolis, MN 55407 USA. [Carter, David K.] St Marys Duluth Clin Hlth System, Dept Pathol, Duluth, MN USA. [Fitzgibbons, Patrick L.] St Jude Med Ctr, Dept Pathol, Fullerton, CA USA. [Frankel, Wendy L.] Ohio State Univ, Med Ctr, Dept Pathol, Columbus, OH 43210 USA. [Jessup, John M.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Kakar, Sanjay] Univ Calif San Francisco, Dept Pathol, San Francisco, CA USA. [Kakar, Sanjay] Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [Minsky, Bruce] Univ Chicago, Dept Radiat Oncol, Chicago, IL 60637 USA. [Nakhleh, Raouf E.] St Lukes Hosp, Dept Pathol, Jacksonville, FL USA. [Compton, Carolyn C.] NCI, Off Biorepositories & Biospecimen Res, Bethesda, MD 20892 USA. RP Washington, MK (reprint author), Vanderbilt Univ, Med Ctr, Dept Pathol, C-3316 MCN, Nashville, TN 37232 USA. EM kay.washington@vanderbilt.edu OI Fitzgibbons, Patrick/0000-0002-2998-6913 NR 41 TC 25 Z9 27 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JUL PY 2008 VL 132 IS 7 BP 1182 EP 1193 PG 12 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 323XH UT WOS:000257481200011 PM 18605770 ER PT J AU Dudgeon, BJ Hoffman, JM Ciol, MA Shumway-Cook, A Yorkston, KM Chan, L AF Dudgeon, Brian J. Hoffman, Jeanne M. Ciol, Marcia A. Shumway-Cook, Anne Yorkston, Kathryn M. Chan, Leighton TI Managing activity difficulties at home: A survey of medicare beneficiaries SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT Joint Conference of the 81st American Congress of Rehabilitation Medicine/11th American-Society-of-NeuroRehabilitation CY SEP 29-OCT 02, 2005 CL Chicago, IL SP Amer Soc Neurorehabilitat DE disabled persons; medicare; rehabilitation ID ASSISTIVE TECHNOLOGY; PERSONAL CARE; OLDER PERSONS; UNMET NEED; LATE-LIFE; DISABILITY; ASSISTANCE; SERVICES; VALIDATION; DEPENDENCE AB Objective: To describe assistance from helpers and use of assistive technology and environmental modification by community-dwelling people with difficulties in activities of daily living (ADLs) and instrumental activities of daily living (IADLs). Design: Cross-sectional study using the 2004 Medicare Current Beneficiary Survey. Setting: Community. Participants: Nationally representative sample of 14,500 Medicare beneficiaries (mean age, 71.5y; 55% female; 49% currently married; 68% living with others; 84% white). Interventions: Not applicable. Main Outcome Measures: Self-reported difficulty with ADLs and IADLs; uses of help, assistive technology, and/or environmental modification. Results: Difficulties were reported most frequently for heavy housework, walking, and shopping; money management, shopping, and light housework were reported as activities most often needing a helper. Walking, bathing, and toileting were activities most often needing uses of assistive technology. Bathroom modifications were the most commonly reported environmental modification. Results from a logistic regression showed that advancing age was the primary factor associated with increasing use of helpers and assistive technology or both for difficult activities. Conclusions: Uses of helpers, assistive technology, and environmental modification are common but vary by type of ADL and/or IADL and age. Focused studies regarding uses of help and access to assistive technology and environmental modification appear needed to support community living. Public education about methods and types of accommodations appears needed and may substitute for or augment guidance from care providers. C1 [Dudgeon, Brian J.; Hoffman, Jeanne M.; Ciol, Marcia A.; Shumway-Cook, Anne; Yorkston, Kathryn M.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Chan, Leighton] Natl Inst Hlth, Clin Res Ctr, Dept Rehabil Med, Bethesda, MD USA. RP Dudgeon, BJ (reprint author), Univ Washington, Dept Rehabil Med, Box 356490, Seattle, WA 98195 USA. EM dudgeonb@u.washington.edu FU Intramural NIH HHS [ZIA CL060072-03]; PHS HHS [MM-0625-04/04] NR 30 TC 9 Z9 9 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JUL PY 2008 VL 89 IS 7 BP 1256 EP 1261 DI 10.1016/j.apmr.2007.11.038 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 323LK UT WOS:000257447400006 PM 18534553 ER PT J AU Yu, L Strandberg, L Lenardo, MJ AF Yu, Li Strandberg, Lindsey Lenardo, Michael J. TI The selectivity of autophagy and its role in cell death and survival SO AUTOPHAGY LA English DT Review DE selectivity; autophagy; macroautophagy; necrosis; nonapoptotic cell death ID VACUOLE TARGETING PATHWAY; YEAST SACCHAROMYCES-CEREVISIAE; CHAPERONE-MEDIATED AUTOPHAGY; MITOCHONDRIAL PROTEIN; CYTOPLASM; DEGRADATION; CARGO; MACHINERY; PEXOPHAGY; PEROXISOMES AB Autophagy is a cellular process whose primary function is to degrade long-lived proteins and recycle cellular components. Beside macroautophagy, there are several forms of selective autophagy, including chaperone-mediated autophagy (CMA), cytoplasm to vacuole targeting (Cvt), pexophagy and mitophagy. In this review, we summarize what is currently known about selective autophagy, and discuss its role in cell death and survival. We also discuss possible mechanisms underlying the selectivity of macroautophagy. C1 [Yu, Li; Strandberg, Lindsey; Lenardo, Michael J.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Lenardo, MJ (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. EM lenardo@nih.gov FU Intramural NIH HHS NR 59 TC 84 Z9 85 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD JUL 1 PY 2008 VL 4 IS 5 BP 567 EP 573 PG 7 WC Cell Biology SC Cell Biology GA 325NW UT WOS:000257596600005 PM 18362514 ER PT J AU Berman, CM Ogawa, H Ionica, C Yin, HB Li, JH AF Berman, Carol M. Ogawa, Hideshi Ionica, Consuel Yin, Huabao Li, Jinhua TI Variation in kin bias over time in a group of Tibetan macaques at Huangshan, China: contest competition, time constraints or risk response? SO BEHAVIOUR LA English DT Article DE kin preferences; grooming networks; time constraints; within-group competition; Macaca thibetana ID MACACA-THIBETANA; SOCIAL-BEHAVIOR; MT. HUANGSHAN; FEMALE PRIMATES; RHESUS-MONKEYS; SQUIRREL-MONKEYS; BABOONS; MODEL; SIZE; EVOLUTION AB We examine variation in grooming kin bias intensity (KBI) among wild female Tibetan macaques (Macaca thibetana hitangshanensis) in one group over time. We test three hypotheses based on socioecological theory, time constraints and risk-related responses. Only the time constraints hypothesis was supported. Grooming KBI was higher when the group was larger, but was unrelated to other indicators of within-group competition. Allies were not necessarily frequent grooming partners; thus, support did not depend on maintaining strong grooming relationships. Females groomed similar amounts, regardless of group size, but groomed smaller percentages of available partners when the group was larger, suggesting that they were unable to maintain grooming relationships with all females as the group expanded. Females with several close kin groomed each of them less than females with few. The lowest ranking females tended to groom close kin almost exclusively, as expected if they had less grooming time to spare than other females. Although grooming KBI was higher when stressful external risks (many humans) were present, the correlation was unsustained when group size was controlled. We suggest that kin-focused grooming networks are shaped at least in part by time constraints and may not be linked directly or indirectly to within-group competition. C1 [Berman, Carol M.; Ionica, Consuel] SUNY Buffalo, Dept Anthropol, Buffalo, NY 14261 USA. [Ogawa, Hideshi] Chukyo Univ, Sch Int Liberal Arts, Aichi 4700393, Japan. [Ionica, Consuel] NICHHD, Comparat Ethol Lab, Poolesville, MD USA. [Yin, Huabao; Li, Jinhua] Anhui Univ, Sch Life Sci, Hefei 230039, Anhui Province, Peoples R China. RP Berman, CM (reprint author), SUNY Buffalo, Dept Anthropol, Buffalo, NY 14261 USA. EM cberman@buffalo.edu RI Ionica, Consuel/A-5186-2009 NR 69 TC 17 Z9 18 U1 2 U2 6 PU BRILL ACADEMIC PUBLISHERS PI LEIDEN PA PLANTIJNSTRAAT 2, P O BOX 9000, 2300 PA LEIDEN, NETHERLANDS SN 0005-7959 J9 BEHAVIOUR JI Behaviour PD JUL PY 2008 VL 145 BP 863 EP 896 DI 10.1163/156853908784089252 PN 7 PG 34 WC Behavioral Sciences; Zoology SC Behavioral Sciences; Zoology GA 305CA UT WOS:000256154200001 ER PT J AU Goldschmidt, AB Tanofsky-Kraff, M Goossens, L Eddy, KT Ringham, R Yanovski, SZ Braet, C Marcus, MD Wilfley, DE Yanovski, JA AF Goldschmidt, Andrea B. Tanofsky-Kraff, Marian Goossens, Lien Eddy, Kamryn T. Ringham, Rebecca Yanovski, Susan Z. Braet, Caroline Marcus, Marsha D. Wilfley, Denise E. Yanovski, Jack A. TI Subtyping children and adolescents with loss of control eating by negative affect and dietary restraint SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE loss of control eating; negative affect; dietary restraint; children; adolescents ID AGE-OF-ONSET; RISK-FACTORS; BULIMIA-NERVOSA; DISORDER EXAMINATION; OBESE CHILDREN; BODY-IMAGE; DEPRESSIVE SYMPTOMS; OVERWEIGHT CHILDREN; AFFECT DIMENSIONS; CLUSTER-ANALYSIS AB Objective: Research suggests that subtyping adults with binge eating disorders by dietary restraint and negative affect predicts comorbid psychopathology, binge eating severity, and treatment outcome. Little research has explored the validity and clinical utility of subtyping youth along these dimensions. Method: Children (aged 8-18 years) reporting loss of control eating (n = 159) were characterized based upon measures of dietary restraint and negative affect using cluster analysis, and then compared regarding disordered eating attitudes and behaviors, and parent-reported behavior problems. Results: Robust subtypes characterized by dietary restraint (n = 114; 71.7%) and dietary restraint/high negative affect (n = 45; 28.3%) emerged. Compared to the former group, the dietary restraint/high negative affect subtype evidenced increased shape and weight concerns, more frequent binge eating episodes, and higher rates of parent-reported problems (all ps < 0.05). Conclusion: Similar to findings from the adult literature, the presence of negative affect may mark a more severe variant of loss of control eating in youth. Future research should explore the impact of dietary restraint/negative affect subtypes on psychiatric functioning, body weight, and treatment outcome. (c) 2008 Elsevier Ltd. All rights reserved. C1 [Goldschmidt, Andrea B.] Washington Univ, Dept Psychol, St Louis, MO 63110 USA. [Tanofsky-Kraff, Marian; Yanovski, Susan Z.; Yanovski, Jack A.] NICHHD, Unit Growth & Obes, PDEGEN, NIH,Hatfield Clin Res Ctr, Bethesda, MD 20892 USA. [Goossens, Lien; Braet, Caroline] Univ Ghent, Dept Dev Personal & Social Psychol, B-9000 Ghent, Belgium. [Eddy, Kamryn T.] Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. [Eddy, Kamryn T.] Childrens Hosp, Boston, MA 02115 USA. [Ringham, Rebecca; Marcus, Marsha D.] Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. [Yanovski, Susan Z.] NIDDK, Bethesda, MD 20892 USA. [Wilfley, Denise E.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. RP Tanofsky-Kraff, M (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM goldscha@psychiatry.wustl.edu; mtanofsky@usuhs.mil; lien.goossens@ugent.be; kamryn@gmail.com; ringhamrm@upmc.edu; yanovskis@extra.niddk.nih.gov; caroline.braet@ugent.be; marcusmd@upmc.edu; wilfleyd@psychiatry.wustl.edu; yanovskj@mail.nih.gov OI Yanovski, Jack/0000-0001-8542-1637 FU Intramural NIH HHS [Z01 HD000641-12, Z99 HD999999]; NHLBI NIH HHS [R24 HL076858, HL076852/076858, R24 HL076852, R24 HL076852-04, R24 HL076858-04, T32 HL007456]; NICHD NIH HHS [T32 HD007456-05, Z01 HD000641, Z01 HD00641]; NIMH NIH HHS [F31 MH071019, F31 MH071019-01A1, K24 MH070446, K24 MH070446-01] NR 66 TC 22 Z9 22 U1 6 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD JUL PY 2008 VL 46 IS 7 BP 777 EP 787 DI 10.1016/j.brat.2008.03.004 PG 11 WC Psychology, Clinical SC Psychology GA 321ZD UT WOS:000257344100001 PM 18460404 ER PT J AU Sengupta, A Carlson, BA Weaver, JA Novoselov, SV Fomenko, DE Gladyshev, VN Hatfield, DL AF Sengupta, Aniruddha Carlson, Bradley A. Weaver, James A. Novoselov, Sergey V. Fomenko, Dmitri E. Gladyshev, Vadim N. Hatfield, Dolph L. TI A functional link between housekeeping selenoproteins and phase II enzymes SO BIOCHEMICAL JOURNAL LA English DT Article DE gene expression; liver; microarray; selenocysteine (Sec) tRNA; Trsp knockout; xenobiotic ID SELENOCYSTEINE TRANSFER-RNA; GLUTATHIONE-PEROXIDASE ACTIVITY; CYTOCHROME-P450 2A5; HEME OXYGENASE-1; GENE TRSP; SELENIUM; EXPRESSION; INDUCTION; LIVER; CHEMOPROTECTION AB See (selenocysteine) is biosynthesized on its tRNA and incorporated into selenium-containing proteins (selenoproteins) as the 21st amino acid residue. Selenoprotein synthesis is dependent on See tRNA and the expression of this class of proteins can be modulated by altering See tRNA expression. The gene encoding Sec tRNA (Trsp) is a single-copy gene and its targeted removal in liver demonstrated that selenoproteins are essential for proper function wherein their absence leads to necrosis and hepatocellular degeneration. In the present study, we found that the complete loss of selenoproteins in liver was compensated for by an enhanced expression of several phase II response genes and their corresponding gene products. The replacement of selenoprotein synthesis in mice carrying mutant Trsp transgenes, wherein housekeeping, but not stress-related selenoproteins are expressed, led to normal expression of phase II response genes. Thus the present study provides evidence for a functional link between housekeeping selenoproteins and phase II enzymes. C1 [Sengupta, Aniruddha; Carlson, Bradley A.; Weaver, James A.; Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, CCR,NIH, Bethesda, MD 20892 USA. [Novoselov, Sergey V.; Fomenko, Dmitri E.; Gladyshev, Vadim N.] Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. RP Hatfield, DL (reprint author), NCI, Mol Biol Selenium Sect, Lab Canc Prevent, CCR,NIH, Bethesda, MD 20892 USA. EM hatfield@mail.nih.gov RI Gladyshev, Vadim/A-9894-2013; OI Novoselov, Sergey/0000-0003-0104-6492 FU Intramural NIH HHS [Z01 BC005317-24]; NIGMS NIH HHS [R01 GM061603, R01 GM061603-06] NR 37 TC 22 Z9 22 U1 0 U2 2 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUL 1 PY 2008 VL 413 BP 151 EP 161 DI 10.1042/BJ20080277 PN 1 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 323YF UT WOS:000257483700015 PM 18373496 ER PT J AU Nakajima, T Tanaka, N Sugiyama, E Kamijo, Y Hara, A Hu, R Li, G Li, YF Nakamura, K Gonzalez, FJ Aoyama, T AF Nakajima, Takero Tanaka, Naoki Sugiyama, Eiko Kamijo, Yuji Hara, Atsushi Hu, Rui Li, Gang Li, Yufeng Nakamura, Kozo Gonzalez, Frank J. Aoyama, Toshifumi TI Cholesterol-lowering effect of bezafibrate is independent of peroxisome proliferator-activated receptor activation in mice SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE bezafibrate; peroxisome proliferator-activated receptor (PPAR); Ppara-null mice; cholesterol metabolism; sterol regulatory element-binding protein (SREBP) 2 ID PRIMARY BILIARY-CIRRHOSIS; ACID-BINDING PROTEIN; ALPHA PPAR-ALPHA; BILE-ACID; HDL CHOLESTEROL; RAT-LIVER; LIPOPROTEIN METABOLISM; GLUCOSE-METABOLISM; LIPID-SYNTHESIS; HEPATIC ABCA1 AB The hypocholesterolemic potential of peroxisome proliferator-activated receptor (PPAR) pan-activator bezafibrate has been documented. However, in addition to uncertainty about the contribution of PPAR alpha to its effect, there is a marked discrepancy in bezafibrate dosages used in previous rodent experiments (>= 50 mg/kg/day) and those in clinical use (<= 10 mg/kg/ day). To investigate the association between bezafibrate-induced cholesterol reduction and PPARa activation, wild-type and Ppara-null mice were treated with bezafibrate at high (100 mg/kg/day) or low (10 mg/kg/day) doses and analyzed. High-dose treatment decreased hepatic cholesterol content in wild-type mice, but increased serum cholesterol concentration. In liver samples, simultaneous increases in the expression of numerous proteins involved in cholesterol biosynthesis and catabolism, as well as cholesterol influx and efflux, were observed, which made interpretation of phenotype changes subtle. These complicated responses were believed to be associated with intensive PPAR activation and accompanying up-regulation of liver X receptor a, farnesoid X receptor, and sterol regulatory element-binding protein 2 (SREBP2). In contrast, low-dose bezafibrate treatment decreased serum and hepatic cholesterol concentrations in a PPAR alpha-independent manner, probably from suppression of SREBP2-regulated cholesterogenesis and enhancement of cholesterol catabolism due to elevated 7 alpha-hydroxylase levels. Interestingly, the low-dose treatment did not affect the expression of PPAR target genes or number of peroxisomes, suggesting the absence of PPAR activation. These results demonstrate that the action of bezafibrate on cholesterol metabolism may vary with dosage, and that the cholesterol-reducing effect found in mice at dosages similar to those administered to humans is independent of significant PPAR activation. (c) 2008 Elsevier Inc. All rights reserved. C1 [Nakajima, Takero; Tanaka, Naoki; Sugiyama, Eiko; Kamijo, Yuji; Hara, Atsushi; Hu, Rui; Li, Gang; Li, Yufeng; Aoyama, Toshifumi] Shinshu Univ, Inst Aging & Adaptat, Dept Metab Regulat, Grad Sch Med, Matsumoto, Nagano 3908621, Japan. [Tanaka, Naoki; Kamijo, Yuji] Shinshu Univ, Sch Med, Dept Internal Med, Matsumoto, Nagano 3908621, Japan. [Sugiyama, Eiko] Nagano Prefectural Coll, Dept Nutr Sci, Nagano, Japan. [Hu, Rui] Hebei Med Univ, Hosp 2, Shijiazhuang, Hebei, Peoples R China. [Li, Gang] Hebei Prov Peoples Hosp, Cardiac Ctr, Shijiazhuang, Hebei, Peoples R China. [Nakamura, Kozo] Shinshu Univ, Fac Agr, Dept Biosci & Biotechnol, Nagano, Japan. [Gonzalez, Frank J.] Natl Canc Inst, Lab Metab, Bethesda, MD USA. RP Tanaka, N (reprint author), Shinshu Univ, Inst Aging & Adaptat, Dept Metab Regulat, Grad Sch Med, 3-1-1 Asahi, Matsumoto, Nagano 3908621, Japan. EM naopi@hsp.md.shinshu-u.ac.jp RI Hara, Atsushi/B-1127-2008 NR 57 TC 15 Z9 16 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JUL 1 PY 2008 VL 76 IS 1 BP 108 EP 119 DI 10.1016/j.bcp.2008.04.001 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 329DN UT WOS:000257847200012 PM 18486101 ER PT J AU Kaila, VRI Verkhovsky, M Hummer, G Wikstrom, M AF Kaila, Ville R. I. Verkhovsky, Michael Hummer, Gerhard Wikstroem, Marten TI Prevention of leak in the proton pump of cytochrome c oxidase SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS LA English DT Article; Proceedings Paper CT 15th European Bioenergetic Conference CY JUL 19-24, 2008 CL Trinity Coll, Dublin, IRELAND HO Trinity Coll DE proton transfer; oxygen reduction; glutamic acid ID HEME-COPPER OXIDASES; LOW-SPIN HEME; PARACOCCUS-DENITRIFICANS; RHODOBACTER-SPHAEROIDES; ELECTRON-TRANSFER; GLUTAMIC ACID-286; SUBUNIT I; DYNAMICS; WATER; TRANSLOCATION AB The cytochrome c oxidases (CcO), which are responsible for Most 02 consumption in biology, are also redoxlinked proton pumps that effectively convert the free energy of 02 reduction to an electrochemical proton gradient across mitochondrial and bacterial membranes. Recently, time-resolved measurements have elucidated the sequence of events in proton translocation, and shed light on the underlying molecular mechanisms. One crucial property of the proton pump mechanism has received less attention, viz. how proton leaks are avoided. Here, we will analyse this topic and demonstrate how the key proton-carrying residue Glu-242 (numbering according to the sequence of subunit I of bovine heart CcO) functions as a valve that has the effect of minimising back-leakage of the pumped proton. (c) 2008 Elsevier B.V. All rights reserved. C1 [Kaila, Ville R. I.; Verkhovsky, Michael; Wikstroem, Marten] Univ Helsinki, Inst Biotechnol, Helsinki Bioenerget Grp, Struct Biol & Biophys Programme, FIN-00014 Helsinki, Finland. [Hummer, Gerhard] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Wikstrom, M (reprint author), Univ Helsinki, Inst Biotechnol, Helsinki Bioenerget Grp, Struct Biol & Biophys Programme, PB65 Viikinkaari 1, FIN-00014 Helsinki, Finland. EM marten.wikstrom@helsinki.fi RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X FU Intramural NIH HHS NR 33 TC 22 Z9 22 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2728 J9 BBA-BIOENERGETICS JI Biochim. Biophys. Acta-Bioenerg. PD JUL-AUG PY 2008 VL 1777 IS 7-8 BP 890 EP 892 DI 10.1016/j.bbabio.2008.03.016 PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 326YU UT WOS:000257696400046 PM 18423393 ER PT J AU Mulkidjanian, AY Dibrov, P Galperin, MY AF Mulkidjanian, Armen Y. Dibrov, Pavel Galperin, Michael Y. TI The past and present of sodium energetics: May the sodium-motive force be with you SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS LA English DT Article; Proceedings Paper CT 15th European Bioenergetic Conference CY JUL 19-24, 2008 CL Trinity Coll, Dublin, IRELAND HO Trinity Coll DE sodium energetics; sodium-motive force; ATP synthase; nanomotors; proton transfer; sodium-dependent transporters; biological membranes; Vibrio cholerae; Chlamydia sp.; anaerobic pathogenic bacteria ID F1F0 ATP SYNTHASES; COMPLETE GENOME SEQUENCE; NA+-TRANSLOCATING NADH; ALKALIPHILIC BACILLUS; ESCHERICHIA-COLI; VIBRIO-CHOLERAE; LIPID-BILAYERS; V-TYPE; OXIDATIVE-PHOSPHORYLATION; ENERGY TRANSDUCTION AB All living cells routinely expel Na+ ions, maintaining lower concentration of Na+ in the cytoplasm than in the surrounding milieu. In the vast majority of bacteria, as well as in mitochondria and chloroplasts, export of Na+ occurs at the expense of the proton-motive force. Some bacteria, however, possess primary generators of the transmembrane electrochemical gradient of Na+ (sodium-motive force). These primary Na+ pumps have been traditionally seen as adaptations to high external pH or to high temperature. Subsequent studies revealed, however, the mechanisms for primary sodium pumping in a variety of non-extremophiles, such as marine bacteria and certain bacterial pathogens. Further, many alkaliphiles and hyperthermophiles were shown to rely on H+, not Na+, as the coupling ion. We review here the recent progress in understanding the role of sodium-motive force, including (i) the conclusion on evolutionary primacy of the sodium-motive force as energy intermediate, (ii) the mechanisms, evolutionary advantages and limitations of switching from Na+ to H+ as the coupling ion, and (iii) the possible reasons why certain pathogenic bacteria Still rely on the sodium-motive force. (C) 2008 Elsevier B.V. All Fights reserved. C1 [Mulkidjanian, Armen Y.] Univ Osnabruck, Sch Phys, D-49069 Osnabruck, Germany. [Mulkidjanian, Armen Y.] Moscow MV Lomonosov State Univ, AN Belozersky Inst Physicochem Biol, Moscow 119991, Russia. [Dibrov, Pavel] Univ Manitoba, Fac Sci, Dept Microbiol, Winnipeg, MB R3T 2N2, Canada. [Galperin, Michael Y.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Mulkidjanian, AY (reprint author), Univ Osnabruck, Sch Phys, D-49069 Osnabruck, Germany. EM amulkid@uos.de; galperin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013; Mulkidjanian, Armen/J-8086-2013 OI Galperin, Michael/0000-0002-2265-5572; Mulkidjanian, Armen/0000-0001-5844-3064 FU Intramural NIH HHS [Z99 LM999999] NR 123 TC 67 Z9 70 U1 3 U2 27 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2728 J9 BBA-BIOENERGETICS JI Biochim. Biophys. Acta-Bioenerg. PD JUL-AUG PY 2008 VL 1777 IS 7-8 BP 985 EP 992 DI 10.1016/j.bbabio.2008.04.028 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 326YU UT WOS:000257696400061 PM 18485887 ER PT J AU Yu, CA Cen, XW Ma, HW Yin, Y Yu, L Esser, L Xia, D AF Yu, Chang-An Cen, Xiaowei Ma, He-Wen Yin, Ying Yu, Linda Esser, Lothar Xia, Di TI Domain conformational switch of the iron-sulfur protein in cytochrome bc(1) complex is induced by the electron transfer from cytochrome b(L) to b(H) SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS LA English DT Article; Proceedings Paper CT 15th European Bioenergetic Conference CY JUL 19-24, 2008 CL Trinity Coll, Dublin, IRELAND HO Trinity Coll DE cytochrome; electron transfer; iron-sulfur protein; inhibitor ID QUINOL OXIDATION SITE; BC1 COMPLEX; Q(O) SITE; HEART-MITOCHONDRIA; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; BOVINE HEART; Q-CYCLE; MOVEMENT; REGION AB Intensive biochemical, biophysical and structural studies of the cytochrome (cyt) bc(1) complex in the past have led to the formulation of the "protonmotive Q-cycle" mechanism for electron and proton transfer in this vitally important complex. The key step of this mechanism is the separation of electrons during the oxidation of a substrate quinol at the Q(P) site with both electrons transferred simultaneously to ISP and cyt b(L) when the extrinsic domain of ISP (ISP-ED) is located at the b-position. Pre-steady state fast kinetic analysis of bc(1) demonstrates that the reduced ISP-ED moves to the c(1)-position to reduce cyt c(1) only after the reduced cyt b(L) is oxidized by cyt b(H). However, the question of how the conformational switch of ISP-ED is initiated remains unanswered. The results obtained from analysis of inhibitory efficacy and binding affinity of two types of Q(P) site inhibitors, Pm and Pf, under various redox states of the bc(1) complex, suggest that the electron transfer from heme b(L) to b(H) is the driving force for the releasing of the reduced ISP-ED from the b-position to c(1)-position to reduce cyt c(1). Published by Elsevier B.V. C1 [Yu, Chang-An] Oklahoma State Univ, Dept Biochem & Mol Biol, Noble Res Ctr 255, Stillwater, OK 74078 USA. [Xia, Di] Natl Canc Inst, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Yu, CA (reprint author), Oklahoma State Univ, Dept Biochem & Mol Biol, Noble Res Ctr 255, Stillwater, OK 74078 USA. EM cayuq@okstate.edu FU Intramural NIH HHS; NIGMS NIH HHS [GM30721] NR 33 TC 16 Z9 17 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2728 J9 BBA-BIOENERGETICS JI Biochim. Biophys. Acta-Bioenerg. PD JUL-AUG PY 2008 VL 1777 IS 7-8 BP 1038 EP 1043 DI 10.1016/j.bbabio.2008.03.033 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 326YU UT WOS:000257696400067 PM 18452702 ER PT J AU Chong, HS Song, HA Ma, X Milenic, DE Brady, ED Lim, S Lee, H Baidoo, K Cheng, D Brechbiel, MW AF Chong, Hyun-Soon Song, Hyun A. Ma, Xiang Milenic, Diane E. Brady, Erik D. Lim, Sooyoun Lee, Haisung Baidoo, Kwamena Cheng, Dengfeng Brechbiel, Martin W. TI Novel bimodal bifunctional ligands for radioimmunotherapy and targeted MRI SO BIOCONJUGATE CHEMISTRY LA English DT Article ID RADIATION CANCER-THERAPY; MONOCLONAL-ANTIBODY; AGENTS; GENERATION; CHELATORS AB The structurally novel bifunctional ligands C-NETA and C-NE3TA, each possessing both acyclic and macrocyclic moieties, were prepared and evaluated as potential chelates for radioimmunotherapy (RIT) and targeted magnetic resonance imaging (MRI). Heptadentate C-NE3TA was fortuitously discovered during the preparation of C-NETA. An optimized synthetic method to C-NETA and C-NE3TA including purification of the polar and tailing reaction intermediates, tert-butyl C-NETA (2) and tert-butyl C-NE3TA (3) using semiprep HPLC was developed. The new Gd(III) complexes of C-NETA and C-NE3TA were prepared as contrast enhancement agents for use in targeted MRI. The T-1 relaxivity data indicate that Gd(C-NETA) and Gd(C-NE3TA) possess higher relaxivity than Gd(C-DOTA), a bifunctional version of a commercially available MRI contrast agent; Gd(DOTA). C-NETA and C-NE3TA were radiolabeled with Lu-177, Y-90, Pb-203, Bi-205/6, and Gd-153; and in vitro stability of the radiolabeled corresponding complexes was assessed in human serum. The in vitro studies indicate that the evaluated radiolabeled complexes were stable in serum for I I days with the exception being the Ph-203 complexes of C-NETA and C-NE3TA, which dissociated in serum. C-NETA and C-NE3TA radiolabeled Lu-177, Y-90, or Gd-153 complexes were further evaluated for in vivo stability in athymic mice and possess excellent or acceptable in vivo biodistribution profile. Bi-205/6-C-NE3TA exhibited extremely rapid blood clearance and low radioactivity level at the normal organs, while Bi-205/6-C-NETA displayed low radioactivity level in the blood and all of the organs except for the kidney where relatively high renal uptake of radioactivity is observed. C-NETA and C-NE3TA were further modified for conjugation to the monoclonal antibody Trastuzumab. C1 [Chong, Hyun-Soon; Song, Hyun A.; Ma, Xiang; Lim, Sooyoun; Lee, Haisung; Cheng, Dengfeng] Illinois Inst Technol, Div Chem, Biol Chem & Phys Sci Dept, Chicago, IL 60616 USA. [Milenic, Diane E.; Brady, Erik D.; Baidoo, Kwamena; Brechbiel, Martin W.] Natl Canc Inst, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD USA. RP Chong, HS (reprint author), Illinois Inst Technol, Div Chem, Biol Chem & Phys Sci Dept, 3101 S Dearborn St,LS 182, Chicago, IL 60616 USA. EM Chong@iit.edu FU Intramural NIH HHS [Z01 SC010051-12, Z01 SC006353-25]; NCI NIH HHS [R01CA112503-01A2, K22CA102637, K22 CA102637, R01 CA112503] NR 26 TC 26 Z9 27 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JUL PY 2008 VL 19 IS 7 BP 1439 EP 1447 DI 10.1021/bc800050x PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 327HT UT WOS:000257720900016 PM 18564868 ER PT J AU Boswell, CA Regino, CAS Baidoo, KE Wong, KJ Bumb, A Xu, H Milenic, DE Kelley, JA Lai, CC Brechbiel, MW AF Boswell, C. Andrew Regino, Celeste A. S. Baidoo, Kwamena E. Wong, Karen J. Bumb, Ambika Xu, Heng Milenic, Diane E. Kelley, James A. Lai, Christopher C. Brechbiel, Martin W. TI Synthesis of a cross-bridged cyclam derivative for peptide conjugation and Cu-64 radiolabeling SO BIOCONJUGATE CHEMISTRY LA English DT Article ID IN-VIVO BEHAVIOR; COPPER(II) COMPLEXES; CRYSTAL-STRUCTURE; AZA-CAGE; PROTON SPONGE; AGENTS; 1,4,7,10-TETRAAZABICYCLO<5.5.3>PENTADECANE; PHARMACOKINETICS; RADIOTHERAPY; PERCHLORATE AB The increased use of copper radioisotopes in radiopharmaceutical applications has created a need for bifunctional chelators (BFCs) that form stable radiocopper complexes and allow covalent attachment to biological molecules. Previous studies have established that 4,11-bis-(carbo-tert-butoxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (H2CB-TE2A), a member of the ethylene "cross-bridged" cyclam (CB-cyclam) class of bicyclic tetraaza macrocycles, forms highly kinetically stable complexes with Cu(II) and is less susceptible to in vivo transchelation than its nonbridged analogue, 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid (TETA). Herein, we report a convenient synthesis of a novel cross-bridged BFC that is structurally analogous to CB-TE2A in that it possesses two coordinating acetate arms, but in addition possesses a third orthogonally protected arm for conjugation to peptides and other targeting agents. Application of this strategy to cross-bridged chelators may also enable the development of even further improved agents for Cu-64-mediated diagnostic positron emission tomography (PET) imaging as well as for targeted radiotherapeutic applications. C1 [Boswell, C. Andrew; Baidoo, Kwamena E.; Bumb, Ambika; Xu, Heng; Milenic, Diane E.; Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Regino, Celeste A. S.; Wong, Karen J.] NCI, Ctr Canc Res, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. [Kelley, James A.; Lai, Christopher C.] NCI, Med Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. RP Brechbiel, MW (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bldg 10,Room B40,10 Ctr Dr, Bethesda, MD 20892 USA. EM maninwb@mail.nih.gov OI Boswell, Charles/0000-0002-0426-9846 FU Intramural NIH HHS [Z01 SC010051-12, Z01 SC006353-25] NR 39 TC 50 Z9 50 U1 1 U2 19 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JUL PY 2008 VL 19 IS 7 BP 1476 EP 1484 DI 10.1021/bc800039e PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 327HT UT WOS:000257720900021 PM 18597510 ER PT J AU Gildersleeve, JC Oyelaran, O Simpson, JT Allred, B AF Gildersleeve, Jeffrey C. Oyelaran, Oyindasola Simpson, John T. Allred, Benjamin TI Improved procedure for direct coupling of carbohydrates to proteins via reductive amination SO BIOCONJUGATE CHEMISTRY LA English DT Article ID MEDICAL APPLICATIONS; VACCINE DEVELOPMENT; MICROARRAYS; OLIGOSACCHARIDES; CANCER; SPECIFICITY; TECHNOLOGY; ANTIBODIES; GLYCOMICS; LECTINS AB Carbohydrate-protein conjugates are utilized extensively in basic research and as immunogens in a variety of bacterial vaccines and cancer vaccines. As a result, there have been significant efforts to develop simple and reliable methods for the construction of these conjugates. While direct coupling via reductive amination is an appealing approach, the reaction is typically very inefficient. In this paper, we report improved reaction conditions providing an approximately 500% increase in yield. In addition to optimizing a series of standard reaction parameters, we found that addition of 500 mM sodium sulfate improves the coupling efficiency. To illustrate the utility of these conditions, a series of high mannose BSA conjugates were produced and incorporated into a carbohydrate microarray. Ligand binding to ConA could be observed and apparent affinity constants (K(d)s) measured using the array were in good agreement with values reported by surface plasmon resonance. The results show that the conditions are suitable for microgram-scale reactions, are compatible with complex carbohydrates, and produce biologically active conjugates. C1 [Gildersleeve, Jeffrey C.; Oyelaran, Oyindasola; Allred, Benjamin] NCI, Ctr Canc Res, Med Chem Lab, NIH, Frederick, MD 21702 USA. [Simpson, John T.] NCI, Prot Chem Lab, Adv Technol Program, SAIC Frederick,Inc, Frederick, MD 21702 USA. RP Gildersleeve, JC (reprint author), NCI, Ctr Canc Res, Med Chem Lab, NIH, 376 Boyles St,Bldg 376,Room 109, Frederick, MD 21702 USA. EM gildersleevej@ncifcrf.gov RI Gildersleeve, Jeffrey/N-3392-2014 FU Intramural NIH HHS [Z01 BC010675-03]; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 29 TC 37 Z9 38 U1 0 U2 25 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JUL PY 2008 VL 19 IS 7 BP 1485 EP 1490 DI 10.1021/bc800153t PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 327HT UT WOS:000257720900022 PM 18597509 ER PT J AU Stojmirovic, A Gertz, EM Altschul, SF Yu, YK AF Stojmirovic, Aleksandar Gertz, E. Michael Altschul, Stephen F. Yu, Yi-Kuo TI The effectiveness of position- and composition-specific gap costs for protein similarity searches SO BIOINFORMATICS LA English DT Article; Proceedings Paper CT 16th ISMB Conference on Intelligent Systems for Molecular Biology CY JUL 19-23, 2008 CL Toronto, CANADA SP ISMB ID HIDDEN MARKOV-MODELS; ACID SUBSTITUTION MATRICES; STATISTICAL SIGNIFICANCE; SEQUENCE ALIGNMENT; DATABASE SEARCHES; ROC ANALYSIS; INSERTIONS; DELETIONS; PERFORMANCE; ALGORITHM AB Motivation: The flexibility in gap cost enjoyed by hidden Markov models (HMMs) is expected to afford them better retrieval accuracy than position-specific scoring matrices (PSSMs). We attempt to quantify the effect of more general gap parameters by separately examining the influence of position- and composition-specific gap scores, as well as by comparing the retrieval accuracy of the PSSMs constructed using an iterative procedure to that of the HMMs provided by Pfam and SUPERFAMILY, curated ensembles of multiple alignments. Results: We found that position-specific gap penalties have an advantage over uniform gap costs. We did not explore optimizing distinct uniform gap costs for each query. For Pfam, PSSMs iteratively constructed from seeds based on HMM consensus sequences perform equivalently to HMMs that were adjusted to have constant gap transition probabilities, albeit with much greater variance. We observed no effect of composition-specific gap costs on retrieval performance. These results suggest possible improvements to the PSI-BLAST protein database search program. C1 [Stojmirovic, Aleksandar; Gertz, E. Michael; Altschul, Stephen F.; Yu, Yi-Kuo] Natl Inst Hlth, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Yu, YK (reprint author), Natl Inst Hlth, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. OI Stojmirovic, Aleksandar/0000-0003-0957-6893; Gertz, E. Michael/0000-0001-8390-4387 FU Intramural NIH HHS [Z99 LM999999] NR 39 TC 2 Z9 3 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD JUL 1 PY 2008 VL 24 IS 13 BP I15 EP I23 DI 10.1093/bioinformatics/btn171 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 319NE UT WOS:000257169700024 PM 18586708 ER PT J AU Wang, Y Zhou, XB Wang, HH Li, K Yao, LX Wong, STC AF Wang, Yuan Zhou, Xiaobo Wang, Honghui Li, King Yao, Lixiu Wong, Stephen T. C. TI Reversible jump MCMC approach for peak identification for stroke SELDI mass spectrometry using mixture model SO BIOINFORMATICS LA English DT Article; Proceedings Paper CT 16th ISMB Conference on Intelligent Systems for Molecular Biology CY JUL 19-23, 2008 CL Toronto, CANADA SP ISMB ID ENHANCED LASER-DESORPTION; TIME-OF-FLIGHT; FEATURE-EXTRACTION; WAVELET TRANSFORM; SPECTRA; SERUM; QUANTIFICATION; IONIZATION; PROTEOMICS; DESORPTION/IONIZATION AB Mass spectrometry (MS) has shown great potential in detecting disease-related biomarkers for early diagnosis of stroke. To discover potential biomarkers from large volume of noisy MS data, peak detection must be performed first. This article proposes a novel automatic peak detection method for the stroke MS data. In this method, a mixture model is proposed to model the spectrum. Bayesian approach is used to estimate parameters of the mixture model, and Markov chain Monte Carlo method is employed to perform Bayesian inference. By introducing a reversible jump method, we can automatically estimate the number of peaks in the model. Instead of separating peak detection into substeps, the proposed peak detection method can do baseline correction, denoising and peak identification simultaneously. Therefore, it minimizes the risk of introducing irrecoverable bias and errors from each substep. In addition, this peak detection method does not require a manually selected denoising threshold. Experimental results on both simulated dataset and stroke MS dataset show that the proposed peak detection method not only has the ability to detect small signal-to-noise ratio peaks, but also greatly reduces false detection rate while maintaining the same sensitivity. C1 [Wang, Yuan; Zhou, Xiaobo; Li, King; Wong, Stephen T. C.] Methodist Hosp, Res Inst, CBI, Houston, TX 77030 USA. [Wang, Yuan; Zhou, Xiaobo; Li, King; Wong, Stephen T. C.] Methodist Hosp, Weill Cornell Med Coll, Dept Radiol, Houston, TX 77030 USA. [Wang, Yuan; Yao, Lixiu] Shanghai Jiao Tong Univ, Sch Elect Informt & Elect Engn, Shanghai 200030, Peoples R China. [Wang, Honghui] NIH, Crit Care Med Dept, Ctr Clin, Bethesda, MD 20892 USA. RP Zhou, XB (reprint author), Methodist Hosp, Res Inst, CBI, 6535 Fannin, Houston, TX 77030 USA. EM XZhou@tmhs.org NR 24 TC 12 Z9 12 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 EI 1460-2059 J9 BIOINFORMATICS JI Bioinformatics PD JUL 1 PY 2008 VL 24 IS 13 BP I407 EP I413 DI 10.1093/bioinformatics/btn143 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 319NE UT WOS:000257169700069 PM 18586741 ER PT J AU Ingvarsen, S Madsen, DH Hillig, T Lund, LR Holmbeck, K Behrendt, N Engelholm, LH AF Ingvarsen, Signe Madsen, Daniel H. Hillig, Thore Lund, Leif R. Holmbeck, Kenn Behrendt, Niels Engelholm, Lars H. TI Dimerization of endogenous MT1-MMP is a regulatory step in the activation of the 72-kDa gelatinase MMP-2 on fibroblasts and fibrosarcoma cells SO BIOLOGICAL CHEMISTRY LA English DT Article DE collagenase; gelatinase A; immunofluorescence; MMP-14; pro-enzyme activation; TIMP-2 ID TYPE-1 MATRIX-METALLOPROTEINASE; HUMAN ENDOTHELIAL-CELLS; IV COLLAGENASE; 1-MATRIX METALLOPROTEINASE; INTERSTITIAL COLLAGENASE; MONOCLONAL-ANTIBODIES; EXTRACELLULAR-MATRIX; EFFICIENT ACTIVATION; DEFICIENT MICE; IN-VIVO AB The secreted gelatinase matrix metalloprotease-2 (MMP-2) and the membrane-anchored matrix metalloprotease MT1-MMP (MMP-14), are central players in pericellular proteolysis in extracellular matrix degradation. In addition to possessing a direct collagenolytic and gelatinolytic activity, these enzymes take part in a cascade pathway in which MT1-MMP activates the MMP-2 proenzyme. This reaction occurs in an interplay with the matrix metalloprotease inhibitor, TIMP-2, and the proposed mechanism involves two molecules of MT1-MMP in complex with one TIMP-2 molecule. We provide positive evidence that proMMP-2 activation is governed by dimerization of MT1-MMP on the surface of fibroblasts and fibrosarcoma cells. Even in the absence of transfection and overexpression, dimerization of MT1-MMP markedly stimulated the formation of active MMP-2 products. The effect demonstrated here was brought about by a monoclonal antibody that binds specifically to MT1-MMP as shown by immunofluorescence experiments. The antibody has no effect on the catalytic activity. The effect on proMMP-2 activation involves MT1-MMP dimerization because it requires the divalent monoclonal antibody, with no effect obtained with monovalent Fab fragments. Since only a negligible level of proMMP-2 activation was obtained with MT1-MMP-expressing cells in the absence of dimerization, our results identify the dimerization event as a critical level of proteolytic cascade regulation. C1 [Ingvarsen, Signe; Madsen, Daniel H.; Hillig, Thore; Lund, Leif R.; Behrendt, Niels; Engelholm, Lars H.] Rigshosp, Finsen Lab Dept 3735, DK-2200 Copenhagen N, Denmark. [Holmbeck, Kenn] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. [Engelholm, Lars H.] Rigshosp, Bartholin Inst Dept 3731, DK-2200 Copenhagen N, Denmark. RP Engelholm, LH (reprint author), Rigshosp, Finsen Lab Dept 3735, Ole Maaloes Vej 5, DK-2200 Copenhagen N, Denmark. EM lhe@finsenlab.dk OI Madsen, Daniel Hargboel/0000-0002-3183-6201; Engelholm, Lars/0000-0002-6616-1232 FU Intramural NIH HHS NR 39 TC 23 Z9 23 U1 0 U2 1 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1431-6730 J9 BIOL CHEM JI Biol. Chem. PD JUL PY 2008 VL 389 IS 7 BP 943 EP 953 DI 10.1515/BC.2008.097 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 320NU UT WOS:000257242600018 PM 18627313 ER PT J AU Wen, SH Ulloa, A Husain, F Horwitz, B Contreras-Vidal, JL AF Wen, Shihua Ulloa, Antonio Husain, Fatima Horwitz, Barry Contreras-Vidal, Jose L. TI Simulated neural dynamics of decision-making in an auditory delayed match-to-sample task SO BIOLOGICAL CYBERNETICS LA English DT Article DE neural network; competitive dynamics; action selection; perceptual decision ID DORSOLATERAL PREFRONTAL CORTEX; SHORT-TERM MEMORY; WORKING-MEMORY; PERCEPTUAL DECISION; PREMOTOR CORTEX; PARIETAL CORTEX; MODEL; NETWORKS; NEURONS; FMRI AB An important goal of research on the cognitive neuroscience of decision-making is to produce a comprehensive model of behavior that flows from perception to action with all of the intermediate steps defined. To understand the mechanisms of perceptual decision-making for an auditory discrimination experiment, we connected a large-scale, neurobiologically realistic auditory pattern recognition model to a three-layer decision-making model and simulated an auditory delayed match-to-sample (DMS) task. In each trial of our simulated DMS task, pairs of stimuli were compared each stimulus being a sequence of three frequency-modulated tonal-contour segments, and a "match" or "nonmatch" button was pressed. The model's simulated response times and the different patterns of neural responses (transient, sustained, increasing) are consistent with experimental data and the simulated neurophysiological activity provides insights into the neural interactions from perception to action in the auditory DMS task. C1 [Contreras-Vidal, Jose L.] Univ Maryland, Sch Publ Hlth, Dept Kinesiol, College Pk, MD 20742 USA. [Contreras-Vidal, Jose L.] Univ Maryland, Sch Publ Hlth, Dept Bioengn, College Pk, MD 20742 USA. [Contreras-Vidal, Jose L.] Univ Maryland, Sch Publ Hlth, Grad Program Neurosci & Cognit Sci, College Pk, MD 20742 USA. [Wen, Shihua] Univ Maryland, Dept Math, College Pk, MD 20742 USA. [Ulloa, Antonio; Husain, Fatima; Horwitz, Barry] NIDCD, Brain Imaging & Modeling Sect, NIH, Bethesda, MD USA. RP Contreras-Vidal, JL (reprint author), Univ Maryland, Sch Publ Hlth, Dept Kinesiol, 2363 HHP Bldg, College Pk, MD 20742 USA. EM pepeum@umd.edu RI Contreras-Vidal, Jose/E-7888-2011; OI Ulloa, Antonio/0000-0002-7554-4542 FU Intramural NIH HHS; NIMHD NIH HHS [MD 217475] NR 46 TC 1 Z9 2 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-1200 J9 BIOL CYBERN JI Biol. Cybern. PD JUL PY 2008 VL 99 IS 1 BP 15 EP 27 DI 10.1007/s00422-008-0234-0 PG 13 WC Computer Science, Cybernetics; Neurosciences SC Computer Science; Neurosciences & Neurology GA 322SH UT WOS:000257395100002 PM 18496711 ER PT J AU Cohen, JD Insel, TR AF Cohen, Jonathan D. Insel, Thomas R. TI Cognitive neuroscience and schizophrenia: Translational research in need of a translator SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID MATRICS C1 [Cohen, Jonathan D.] Princeton Univ, Ctr Study Brain, Dept Psychol, Princeton, NJ 08544 USA. [Cohen, Jonathan D.] Princeton Univ, Inst Neurosci, Princeton, NJ 08544 USA. [Insel, Thomas R.] NIMH, Bethesda, MD 20892 USA. RP Cohen, JD (reprint author), Princeton Univ, Ctr Study Brain, Dept Psychol, Green Hall 3-N-8, Princeton, NJ 08544 USA. EM jdc@princeton.edu NR 4 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUL 1 PY 2008 VL 64 IS 1 BP 2 EP 3 DI 10.1016/j.biopsych.2008.04.031 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 314CE UT WOS:000256785500001 PM 18549873 ER PT J AU Carter, CS Barch, DM Buchanan, RW Bullmore, ET Krystal, JH Cohen, J Geyer, M Green, M Nuechterlein, KH Robbins, T Silverstein, S Smith, EE Strauss, M Wykes, T Heinssen, R AF Carter, Cameron S. Barch, Deanna M. Buchanan, Robert W. Bullmore, Edward T. Krystal, John H. Cohen, Jonathan Geyer, Mark Green, Michael Nuechterlein, Keith H. Robbins, Trevor Silverstein, Steven Smith, Edward E. Strauss, Milton Wykes, Til Heinssen, Robert TI Identifying cognitive mechanisms targeted for treatment development in schizophrenia: An overview of the first meeting of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia initiative SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material DE cognitive neuroscience; schizophrenia; translational research; treatment development ID BATTERY AB This overview describes the generation and development of the ideas that led to the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative. It also describes the organization, process, and products of the first meeting. The CNTRICS initiative involves a series of three conferences that will systematically address barriers to translating paradigms developed in the basic animal and human cognitive neuroscience fields for use in translational research aimed at developing novel treatments for cognitive impairments in schizophrenia. The articles in this special section report on the results of the first conference, which used a criterion-based consensus-building process to develop a set of cognitive constructs to be targeted for translation efforts. C1 [Carter, Cameron S.] Univ Calif Davis, UC Davis Imaging Res Ctr, Dept Psychiat, Sacramento, CA 95817 USA. [Barch, Deanna M.] Washington Univ, Dept Psychiat, St Louis, MO USA. [Buchanan, Robert W.] Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. [Bullmore, Edward T.] Univ Cambridge, Dept Psychiat, Cambridge, England. [Krystal, John H.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Cohen, Jonathan] Princeton Univ, Dept Psychol, Princeton, NJ 08544 USA. [Geyer, Mark] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Green, Michael] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA 90024 USA. [Robbins, Trevor] Univ Cambridge, Dept Psychol, Cambridge, England. [Silverstein, Steven] Univ Med & Dent New Jersey, New Brunswick, NJ USA. [Smith, Edward E.] Columbia Univ, Dept Psychol, New York, NY 10027 USA. [Strauss, Milton] Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. [Wykes, Til] Inst Psychiat, Dept Psychiat, London SE5 8AF, England. [Heinssen, Robert] NIMH, Bethesda, MD 20892 USA. RP Carter, CS (reprint author), Univ Calif Davis, UC Davis Imaging Res Ctr, Dept Psychiat, 4701 X St, Sacramento, CA 95817 USA. EM cameron.carter@ucdmc.ucdavis.edu RI Wykes, Til/B-7894-2008; Wykes, Til/B-3812-2011; Barch, Deanna/G-8638-2013; Bullmore, Edward/C-1706-2012 OI Wykes, Til/0000-0002-5881-8003; Bullmore, Edward/0000-0002-8955-8283 FU Medical Research Council [G0001354]; NIMH NIH HHS [R13 MH078710-01, R13 MH078710] NR 6 TC 106 Z9 111 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUL 1 PY 2008 VL 64 IS 1 BP 4 EP 10 DI 10.1016/j.biopsych.2008.03.020 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 314CE UT WOS:000256785500002 PM 18466880 ER PT J AU Hou, SB Makarova, KS Saw, JHW Senin, P Ly, BV Zhou, ZM Ren, Y Wang, JM Galperin, MY Omelchenko, MV Wolf, YI Yutin, N Koonin, EV Stott, MB Mountain, BW Crowe, MA Smirnova, AV Dunfield, PF Feng, L Wang, L Alam, M AF Hou, Shaobin Makarova, Kira S. Saw, Jimmy H. W. Senin, Pavel Ly, Benjamin V. Zhou, Zhemin Ren, Yan Wang, Jianmei Galperin, Michael Y. Omelchenko, Marina V. Wolf, Yuri I. Yutin, Natalya Koonin, Eugene V. Stott, Matthew B. Mountain, Bruce W. Crowe, Michelle A. Smirnova, Angela V. Dunfield, Peter F. Feng, Lu Wang, Lei Alam, Maqsudul TI Complete genome sequence of the extremely acidophilic methanotroph isolate V4, Methylacidiphilum infernorum, a representative of the bacterial phylum Verrucomicrobia SO BIOLOGY DIRECT LA English DT Article ID METHYLOBACTERIUM-EXTORQUENS AM1; HORIZONTAL GENE-TRANSFER; NUCLEAR-PORE-COMPLEX; ESCHERICHIA-COLI; HELICOBACTER-PYLORI; METHANE OXIDATION; SURROGATE METHODS; RNA GENES; SP NOV.; EVOLUTION AB Background: The phylum Verrucomicrobia is a widespread but poorly characterized bacterial clade. Although cultivation-independent approaches detect representatives of this phylum in a wide range of environments, including soils, seawater, hot springs and human gastrointestinal tract, only few have been isolated in pure culture. We have recently reported cultivation and initial characterization of an extremely acidophilic methanotrophic member of the Verrucomicrobia, strain V4, isolated from the Hell's Gate geothermal area in New Zealand. Similar organisms were independently isolated from geothermal systems in Italy and Russia. Results: We report the complete genome sequence of strain V4, the first one from a representative of the Verrucomicrobia. Isolate V4, initially named "Methylokorus infernorum" ( and recently renamed Methylacidiphilum infernorum) is an autotrophic bacterium with a streamlined genome of similar to 2.3 Mbp that encodes simple signal transduction pathways and has a limited potential for regulation of gene expression. Central metabolism of M. infernorum was reconstructed almost completely and revealed highly interconnected pathways of autotrophic central metabolism and modifications of C(l)-utilization pathways compared to other known methylotrophs. The M. infernorum genome does not encode tubulin, which was previously discovered in bacteria of the genus Prosthecobacter, or close homologs of any other signature eukaryotic proteins. Phylogenetic analysis of ribosomal proteins and RNA polymerase subunits unequivocally supports grouping Planctomycetes, Verrucomicrobia and Chlamydiae into a single clade, the PVC superphylum, despite dramatically different gene content in members of these three groups. Comparative-genomic analysis suggests that evolution of the M. infernorum lineage involved extensive horizontal gene exchange with a variety of bacteria. The genome of M. infernorum shows apparent adaptations for existence under extremely acidic conditions including a major upward shift in the isoelectric points of proteins. Conclusion: The results of genome analysis of M. infernorum support the monophyly of the PVC superphylum. M. infernorum possesses a streamlined genome but seems to have acquired numerous genes including those for enzymes of methylotrophic pathways via horizontal gene transfer, in particular, from Proteobacteria. C1 [Zhou, Zhemin; Ren, Yan; Wang, Jianmei; Feng, Lu; Wang, Lei] Nankai Univ, TEDA Sch Biol Sci & Biotechnol, Tianjin 300457, Peoples R China. [Hou, Shaobin; Saw, Jimmy H. W.; Senin, Pavel; Ly, Benjamin V.; Alam, Maqsudul] Univ Hawaii, Coll Nat Sci, Adv Studies Genom Prote & Bioinformat, Honolulu, HI 96822 USA. [Makarova, Kira S.; Galperin, Michael Y.; Omelchenko, Marina V.; Wolf, Yuri I.; Yutin, Natalya; Koonin, Eugene V.] Natl Inst Hlth, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Mountain, Bruce W.; Crowe, Michelle A.; Smirnova, Angela V.; Dunfield, Peter F.] Wairakei Res Ctr, Inst Geol & Nucl Sci, Taupo, New Zealand. [Dunfield, Peter F.] Univ Calgary, Dept Biol Sci, Calgary, AB T2N 1N4, Canada. [Wang, Lei] Nankai Univ, Coll Life Sci, Minist Educ, Key Lab Mol Microbiol & Technol, Tianjin 300071, Peoples R China. [Saw, Jimmy H. W.; Alam, Maqsudul] Univ Hawaii, Dept Microbiol, Honolulu, HI 96822 USA. [Saw, Jimmy H. W.; Senin, Pavel] Los Alamos Natl Lab, Biosci Div, Los Alamos, NM 87545 USA. RP Wang, L (reprint author), Nankai Univ, TEDA Sch Biol Sci & Biotechnol, Tianjin 300457, Peoples R China. EM shaobin@hawaii.edu; makarova@ncbi.nlm.nih.gov; jsaw@lanl.gov; seninp@gmail.com; binhl@hawaii.edu; jemmings@gmail.com; renyan198211@hotmail.com; jianmei_0311@hotmail.com; galperin@ncbi.nlm.nih.gov; omelchen@ncbi.nlm.nih.gov; m.stott@gns.cri.nz; b.mountain@gns.cri.nz; koonin@ncbi.nlm.nih.gov; m.stott@gns.cri.nz; b.mountain@gns.cri.nz; m.crowe@gns.cri.nz; angelasmirnova@hotmail.com; pfdunfie@ucalgary.ca; fenglu63@nankai.edu.cn; wanglei@nankai.edu.cn; alam@hawaii.edu RI Wang, Lei/C-5176-2009; Saw, Jimmy/A-9972-2009; feng, lu/M-5113-2015; Dunfield, Peter/C-3105-2009; Galperin, Michael/B-5859-2013; OI Saw, Jimmy/0000-0001-8353-3854; Galperin, Michael/0000-0002-2265-5572; Senin, Pavel/0000-0001-5517-7768; Hou, Shaobin/0000-0003-3467-8242 FU Intramural NIH HHS [Z99 LM999999] NR 100 TC 83 Z9 198 U1 2 U2 43 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD JUL 1 PY 2008 VL 3 AR 26 DI 10.1186/1745-6150-3-26 PG 25 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 328NH UT WOS:000257804600001 PM 18593465 ER PT J AU Odet, F Duan, CW Willis, WD Goulding, EH Kung, A Eddy, EM Goldberg, E AF Odet, Fanny Duan, Chongwen Willis, William D. Goulding, Eugenia H. Kung, Aisha Eddy, Edward M. Goldberg, Erwin TI Expression of the gene for mouse lactate dehydrogenase C (Ldhc) is required for male fertility SO BIOLOGY OF REPRODUCTION LA English DT Article DE capacitation; fertilization; gamete biology sperm; gene targeting; glycolysis; mouse; sperm capacitation; sperm motility and transport; testis ID PROTEIN-TYROSINE PHOSPHORYLATION; SPERM IN-VITRO; CAPACITATION; SPERMATOZOA; MOTILITY; GLUCOSE; TESTIS; CELLS; FERTILIZATION; BICARBONATE AB The lactate dehydrogenase (LDH) protein family members characteristically are distributed in tissue- and cell type-specific patterns and serve as the terminal enzyme of glycolysis, catalyzing reversible oxidation reduction between pyruvate and lactate. They are present as tetramers, and one family member, LDHC, is abundant in spermatocytes, spermatids, and sperm, but also is found in modest amounts in oocytes. We disrupted the Ldhc gene to determine whether LDHC is required for spermatogenesis, oogenesis, and/or sperm and egg function. The targeted disruption of Ldhc severely impaired fertility in male Ldhc(-/-) mice but not in female Ldhc(-/-) mice. Testis and sperm morphology and sperm production appeared to be normal. However, total LDH enzymatic activity was considerably lower in Ldhc(-/-) sperm than in wild type sperm, indicating that the LDHC homotetramer (LDH-C(4)) is responsible for most of the LDH activity in sperm. Although initially motile when isolated, there was a more rapid reduction in the level of ATP and in motility in Ldhc(-/-) sperm than in wild-type sperm. Moreover, Ldhc(-/-) sperm did not acquire hyperactivated motility, were unable to penetrate the zona pellucida in vitro, and failed to undergo the phosphorylation events characteristic of capacitation. These studies showed that LDHC plays an essential role in maintenance of the processes of glycolysis and ATP production in the flagellum that are required for male fertility and sperm function. C1 [Duan, Chongwen; Kung, Aisha; Goldberg, Erwin] Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60208 USA. [Odet, Fanny; Willis, William D.; Goulding, Eugenia H.] NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Goldberg, E (reprint author), Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60208 USA. EM erv@northwestern.edu FU Intramural NIH HHS; NICHD NIH HHS [R01 HD005863-35, HD05863, R01 HD005863] NR 39 TC 88 Z9 96 U1 0 U2 7 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JUL PY 2008 VL 79 IS 1 BP 26 EP 34 DI 10.1095/biolreprod.108.068353 PG 9 WC Reproductive Biology SC Reproductive Biology GA 316LK UT WOS:000256950900004 PM 18367675 ER PT J AU Rodriguez-Miranda, E Buffone, MG Edwards, SE Ord, TS Lin, K Sammel, MD Gerton, GL Moss, SB Williams, CJ AF Rodriguez-Miranda, Esmeralda Buffone, Mariano G. Edwards, Scott E. Ord, Teri S. Lin, Kathleen Sammel, Mary D. Gerton, George L. Moss, Stuart B. Williams, Carmen J. TI Extracellular adenosine 5 '-triphosphate alters motility and improves the fertilizing capability of mouse sperm SO BIOLOGY OF REPRODUCTION LA English DT Article DE acrosomal exocytosis; acrosome reaction; assisted reproductive technology; extracellular ATP; fertilization; hyperactivation; intracellular calcium; purinergic receptor; sperm motility and transport ID PROTEIN-TYROSINE PHOSPHORYLATION; CILIATED CELLS; CA2+; SPERMATOZOA; RECEPTORS; ACTIVATION; CAMP; ATP; PURINOCEPTOR; INFERTILITY AB Extracellular adenosine 5'-triphosphate (ATPe) treatment of human sperm has been implicated in improving in vitro fertilization (IVF) results. We used the mouse model to investigate mechanisms of action of ATPe on sperm. ATPe treatment significantly enhanced IVF success as indicated by both rate of pronuclear formation and percentage cleavage to the 2-cell stage. However, ATPe did not increase the percentage of sperm undergoing spontaneous acrosomal exocytosis nor change the pattern of protein tyrosine phosphorylation normally observed in capacitated sperm. ATPe altered sperm motility parameters; in particular, both noncapacitated and capacitated sperm swam faster and straighter. The percentage of hyper-activated sperm did not increase in capacitated ATPe-treated sperm compared to control sperm. ATPe induced a rapid increase in the level of intracellular calcium that was inhibited by two distinct P2 purinergic receptor inhibitors, confirming that these receptors have an ionotropic role in sperm function. The observed motility changes likely explain, in part, the improved fertilizing capability when ATPe-treated sperm were used in IVF procedures and suggest a mechanism by which ATPe treatment may be beneficial for artificial reproductive techniques. C1 [Rodriguez-Miranda, Esmeralda; Buffone, Mariano G.; Edwards, Scott E.; Ord, Teri S.; Lin, Kathleen; Sammel, Mary D.; Gerton, George L.; Moss, Stuart B.; Williams, Carmen J.] Univ Penn, Dept Obstet & Gynecol, Ctr Res Reprod & Womens Hlth, Philadelphia, PA 19104 USA. [Sammel, Mary D.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Williams, CJ (reprint author), NIEHS, POB 12233,MD E4-05, Res Triangle Pk, NC 27709 USA. EM williamsc5@niehs.nih.gov RI Gerton, George/A-1039-2007; Williams, Carmen/E-2170-2013 OI Gerton, George/0000-0001-9894-5640; Williams, Carmen/0000-0001-6440-7086 FU FIC NIH HHS [D43-TW00671]; NICHD NIH HHS [HD41552] NR 35 TC 26 Z9 28 U1 0 U2 6 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JUL PY 2008 VL 79 IS 1 BP 164 EP 171 DI 10.1095/biolreprod.107.065565 PG 8 WC Reproductive Biology SC Reproductive Biology GA 316LK UT WOS:000256950900019 PM 18401012 ER PT J AU Chruszcz, M Wlodawer, A Minor, W AF Chruszcz, Maksymilian Wlodawer, Alexander Minor, Wladek TI Determination of protein structures - A series of fortunate events SO BIOPHYSICAL JOURNAL LA English DT Review ID RESOLUTION CRYSTAL-STRUCTURE; NERVE GROWTH-FACTOR; LON PROTEASES; MACROMOLECULAR STRUCTURES; AFFINITY-CHROMATOGRAPHY; RECOMBINANT PROTEINS; CRYSTALLIZATION; CRYSTALLOGRAPHY; REFINEMENT; GENOMICS AB Determination of a macromolecular structure using x-ray diffraction is a multistep process that involves a plethora of techniques involving molecular biology, bioinformatics, and physical sciences. Counterintuitively, the success of any or all individual steps does not guarantee the success of the overall process. This review examines the difficulties presented by each step on the path from a gene to the final publication, together with certain lucky (or unlucky) circumstances that can affect the velocity along that path. C1 [Chruszcz, Maksymilian; Minor, Wladek] Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22903 USA. [Wlodawer, Alexander] NCI, Macromol Crystallog Lab, Prot Struct Sect, Frederick, MD 21701 USA. RP Minor, W (reprint author), Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22903 USA. EM wladek@iwonka.med.virginia.edu RI Chruszcz, Maksymilian/E-6407-2011; Minor, Wladek/F-3096-2014; OI Chruszcz, Maksymilian/0000-0001-7521-5485; Minor, Wladek/0000-0001-7075-7090 FU Intramural NIH HHS; NIGMS NIH HHS [GM53163, GM74942, R01 GM053163, U54 GM074942] NR 72 TC 20 Z9 22 U1 0 U2 17 PU BIOPHYSICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL 1 PY 2008 VL 95 IS 1 BP 1 EP 9 DI 10.1529/biophysj.108.131789 PG 9 WC Biophysics SC Biophysics GA 312JR UT WOS:000256668200005 PM 18441029 ER PT J AU Milescu, LS Yamanishi, T Ptak, K Mogri, MZ Smith, JC AF Milescu, Lorin S. Yamanishi, Tadashi Ptak, Krzysztof Mogri, Murtaza Z. Smith, Jeffrey C. TI Real-time kinetic modeling of voltage-gated ion channels using dynamic clamp SO BIOPHYSICAL JOURNAL LA English DT Article ID CEREBELLAR PURKINJE NEURONS; AGGREGATED MARKOV-MODELS; AXON INITIAL SEGMENT; SINGLE-CHANNEL; WHOLE-CELL; STOCHASTIC SIMULATION; MACROSCOPIC CURRENTS; PYRAMIDAL NEURONS; SODIUM CURRENTS; NA+ CHANNELS AB We propose what to our knowledge is a new technique for modeling the kinetics of voltage-gated ion channels in a functional context, in neurons or other excitable cells. The principle is to pharmacologically block the studied channel type, and to functionally replace it with dynamic clamp, on the basis of a computational model. Then, the parameters of the model are modified in real time (manually or automatically), with the objective of matching the dynamical behavior of the cell (e.g., action potential shape and spiking frequency), but also the transient and steady-state properties of the model (e.g., those derived from voltage-clamp recordings). Through this approach, one may find a model and parameter values that explain both the observed cellular dynamics and the biophysical properties of the channel. We extensively tested the method, focusing on Na-v models. Complex Markov models (10-12 states or more) could be accurately integrated in real time at >50 kHz using the transition probability matrix, but not the explicit Euler method. The practicality of the technique was tested with experiments in raphe pacemaker neurons. Through automated real-time fitting, a Hodgkin-Huxley model could be found that reproduced well the action potential shape and the spiking frequency. Adding a virtual axonal compartment with a high density of Na-v channels further improved the action potential shape. The computational procedure was implemented in the free QuB software, running under Microsoft Windows and featuring a friendly graphical user interface. C1 [Milescu, Lorin S.; Yamanishi, Tadashi; Ptak, Krzysztof; Mogri, Murtaza Z.; Smith, Jeffrey C.] Natl Inst Hlth, NINDS, Cellular & Syst Neurobiol Sect, Bethesda, MD 20892 USA. RP Milescu, LS (reprint author), Natl Inst Hlth, NINDS, Cellular & Syst Neurobiol Sect, Bethesda, MD 20892 USA. EM milescul@ninds.nih.gov FU Intramural NIH HHS; NINDS NIH HHS [R01 NS057815-03, R01 NS057815] NR 50 TC 33 Z9 36 U1 0 U2 8 PU BIOPHYSICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL 1 PY 2008 VL 95 IS 1 BP 66 EP 87 DI 10.1529/biophysj.107.118190 PG 22 WC Biophysics SC Biophysics GA 312JR UT WOS:000256668200011 PM 18375511 ER PT J AU Bennett, KM Shapiro, EM Sotak, CH Koretsky, AP AF Bennett, Kevin M. Shapiro, Erik M. Sotak, Christopher H. Koretsky, Alan P. TI Controlled aggregation of ferritin to modulate MRI relaxivity SO BIOPHYSICAL JOURNAL LA English DT Article ID CONTRAST AGENTS; TRANSVERSE RELAXATION; SPLEEN FERRITIN; GENE-EXPRESSION; ACTIN; REPORTER; LIVER; WATER; MAGNETOFERRITIN; SUSCEPTIBILITY AB Ferritin is an iron storage protein expressed in varying concentrations in mammalian cells. The deposition of ferric iron in the core of ferritin makes it a magnetic resonance imaging contrast agent, and ferritin has recently been proposed as a gene expression reporter protein for magnetic resonance imaging. To date, ferritin has been overexpressed in vivo and has been coexpressed with transferrin receptor to increase iron loading in cells. However, ferritin has a relatively low T-2 relaxivity (R-2 approximate to 1 mM(-1) s(-1)) at typical magnetic field strengths and so requires high levels of expression to be detected. One way to modulate the transverse relaxivity of a superparamagnetic agent is to cause it to aggregate, thereby manipulating the magnetic field gradients through which water diffuses. In this work, it is demonstrated by computer simulation and in vitro that aggregation of ferritin can alter relaxivity. The effects of aggregate size and intraaggregate perturber spacing on R-2 are studied. Computer modeling indicates that the optimal spacing of the ferritin molecules in aggregate for increasing R-2 is 100-200 nm for a typical range of water diffusion rates. Chemical cross-linking of ferritin at 12 angstrom spacing led to a 70% increase in R-2 compared to uncross-linked ferritin controls. To modulate ferritin aggregation in a potentially biologically relevant manner, ferritin was attached to actin and polymerized in vitro. The polymerization of ferritin-F-actin caused a 20% increase in R-2 compared to unpolymerized ferritin-G-actin. The R-2-value was increased by another 10% by spacing the ferritin farther apart on the actin. laments. The modulation of ferritin aggregation by binding to cytoskeletal elements may be a useful strategy to make a functional reporter gene for magnetic resonance imaging. C1 [Bennett, Kevin M.; Koretsky, Alan P.] NINDS, Lab Funct & Mol Imaging, Natl Inst Hlth, Bethesda, MD 20892 USA. [Shapiro, Erik M.] Yale Univ, Dept Radiol, New Haven, CT USA. [Sotak, Christopher H.] Worcester Polytech Univ, Dept Biomed Engn, Worcester, MA USA. [Sotak, Christopher H.] Worcester Polytech Univ, Dept Chem & Biochem, Worcester, MA USA. [Sotak, Christopher H.] Univ Massachusetts, Sch Med, Dept Radiol, Worcester, MA USA. RP Koretsky, AP (reprint author), NINDS, Lab Funct & Mol Imaging, Natl Inst Hlth, Bldg 10,Room B1D728,10 Ctr Dr,MSC 1065, Bethesda, MD 20892 USA. RI Koretsky, Alan/C-7940-2015 OI Koretsky, Alan/0000-0002-8085-4756 FU Intramural NIH HHS [Z01 NS003047-01] NR 38 TC 31 Z9 31 U1 0 U2 11 PU BIOPHYSICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL 1 PY 2008 VL 95 IS 1 BP 342 EP 351 DI 10.1529/biophysj.107.116145 PG 10 WC Biophysics SC Biophysics GA 312JR UT WOS:000256668200034 PM 18326661 ER PT J AU Best, RB Buchete, NV Hummer, G AF Best, Robert B. Buchete, Nicolae-Viorel Hummer, Gerhard TI Are current molecular dynamics force fields too helical? SO BIOPHYSICAL JOURNAL LA English DT Article ID PROTEIN BACKBONE; EXPLICIT SOLVENT; SIMULATIONS; PEPTIDES; PARAMETERS; CONFORMATION; STATES AB Accurate force fields are essential for the success of molecular dynamics simulations. In apparent contrast to the conformational preferences of most force fields, recent NMR experiments suggest that short polyalanine peptides in water populate the polyproline II structure almost exclusively. To investigate this apparent contradiction, with its rami. cations for the assessment of molecular force fields and the structure of unfolded proteins, we performed extensive simulations of Ala(5) in water (similar to 5 mu s total time), using twelve different force fields and three different peptide terminal groups. Using either empirical or density-functional-based Karplus relations for the J-couplings, we find that most current force fields do overpopulate the alpha-region, with quantitative results depending on the choice of Karplus relation and on the peptide termini. Even after reweighting to match experiment, we find that Ala(5) retains significant alpha- and beta-populations. In fact, several force fields match the experimental data well before reweighting and have a significant helical population. We conclude that radical changes to the best current force fields are not necessary, based on the NMR data. Nevertheless, experiments on short peptides open the way toward the systematic improvement of current simulation models. C1 [Best, Robert B.; Buchete, Nicolae-Viorel; Hummer, Gerhard] NIH, NIDDK, Chem Phys Lab, Bethesda, MD 20892 USA. RP Hummer, G (reprint author), NIH, NIDDK, Chem Phys Lab, Bldg 5,Rm 132, Bethesda, MD 20892 USA. EM hummer@helix.nih.gov RI Hummer, Gerhard/A-2546-2013; Buchete, Nicolae-Viorel/C-6200-2015; Best, Robert/H-7588-2016 OI Hummer, Gerhard/0000-0001-7768-746X; Buchete, Nicolae-Viorel/0000-0001-9861-1157; Best, Robert/0000-0002-7893-3543 FU Intramural NIH HHS NR 24 TC 233 Z9 233 U1 6 U2 54 PU BIOPHYSICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL 1 PY 2008 VL 95 IS 1 BP L7 EP L9 DI 10.1529/biophysj.108.132696 PG 3 WC Biophysics SC Biophysics GA 312JR UT WOS:000256668200003 PM 18456823 ER PT J AU Zheng, G Ng, HKT AF Zheng, Gang Ng, Hon Keung Tony TI Genetic model selection in two-phase analysis for case-control association studies SO BIOSTATISTICS LA English DT Article DE Cochran-Armitage trend test; disease risk; efficiency robustness; Hardy-Weinberg disequilibrium; SNP ID HARDY-WEINBERG DISEQUILIBRIUM; EFFICIENCY ROBUST-TESTS; SAMPLE-SIZE; POPULATION STRATIFICATION; CONTINGENCY-TABLES; GENOMIC CONTROL; LINKAGE TESTS; AFFECTED SIBS; TREND TESTS; SURVIVAL AB The Cochran-Armitage trend test (CATT) is well suited for testing association between a marker and a disease in case-control studies. When the underlying genetic model for the disease is known, the CATT optimal for the genetic model is used. For complex diseases, however, the genetic models of the true disease loci are unknown. In this situation, robust tests are preferable. We propose a two-phase analysis with model selection for the case-control design. In the first phase, we use the difference of Hardy-Weinberg disequilibrium coefficients between the cases and the controls for model selection. Then, an optimal CATT corresponding to the selected model is used for testing association. The correlation of the statistics used for selection and the test for association is derived to adjust the two-phase analysis with control of the Type-I error rate. The simulation studies show that this new approach has greater efficiency robustness than the existing methods. C1 [Ng, Hon Keung Tony] So Methodist Univ, Dept Stat Sci, Dallas, TX 75275 USA. [Zheng, Gang] NHLBI, Off Biostatist Res, Bethesda, MD 20892 USA. RP Ng, HKT (reprint author), So Methodist Univ, Dept Stat Sci, 3225 Daniel Ave,POB 750332, Dallas, TX 75275 USA. EM ngh@mail.smu.edu NR 31 TC 49 Z9 51 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD JUL PY 2008 VL 9 IS 3 BP 391 EP 399 DI 10.1093/biostatistics/kxm039 PG 9 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 316VE UT WOS:000256977000001 PM 18003629 ER PT J AU Spurrier, B Honkanen, P Holway, A Kumamoto, K Terashima, M Takenoshita, S Wakabayashi, G Austin, J Nishizuka, S AF Spurrier, Brett Honkanen, Peter Holway, Antonia Kumamoto, Kensuke Terashima, Masanori Takenoshita, Seiichi Wakabayashi, Go Austin, John Nishizuka, Satoshi TI Protein and lysate array technologies in cancer research SO BIOTECHNOLOGY ADVANCES LA English DT Review DE protein microarray; theoretical models; cancer research; protein quantitation ID IMMUNOSORBENT-ASSAY ELISA; MULTIANALYTE MICROSPOT IMMUNOASSAY; MICROANALYTICAL COMPACT-DISK; GENE-EXPRESSION PATTERNS; P53-MDM2 FEEDBACK LOOP; SYSTEMS-BIOLOGY; REVERSE-PHASE; DRUG DISCOVERY; ANTIBODY MICROARRAY; INTERACTION NETWORK AB Capturing quantitative proteomic information provides new insights for enhancing the understanding of cancer biology. There have been several protein microarray formats, and each has an advantage depending on what is being detected. However, in contrast to nucleoticle printing, the production of protein arrays generally requires the capability of handling viscous solutions, and the mishandling of various factors, such as temperature and humidity, adversely affect protein status. The requirement for such specifications is critical when increasing the throughput for monitoring a large number of samples for rigorous quantitation. In particular, a new solid pin arrayer has been extremely powerful when highly viscous cell lysates printed for high-density, "reverse-phase" protein arrays, and acquired data allows for theoretical models of protein signaling networks to be constructed. In this review, applications of currently available protein microarray technology to cancer research are discussed including the advantages of the new solid pin architecture for opening up powerful proteomic applications. (c) 2008 Elsevier Inc. All rights reserved. C1 [Spurrier, Brett; Nishizuka, Satoshi] NCI, Mol Therapeut Program, Bethesda, MD 20892 USA. [Kumamoto, Kensuke] NCI, Mol Carcinogenesis Lab, Bethesda, MD 20892 USA. [Spurrier, Brett; Honkanen, Peter; Holway, Antonia; Austin, John] Aushon BioSyst, Billerica, MA 01821 USA. [Kumamoto, Kensuke; Takenoshita, Seiichi] Fukushima Med Univ, Dept Surg 2, Sch Med, Fukushima 9601295, Japan. [Terashima, Masanori] Fukushima Med Univ, Sch Med, Dept Surg 1, Fukushima 9601295, Japan. [Terashima, Masanori] Fukushima Med Univ, Sch Med, Tumor Ctr, Fukushima 9601295, Japan. [Nishizuka, Satoshi] NCI, SAIC Frederick Inc, Lab Prote & Analyt Technol, Frederick, MD 21702 USA. [Wakabayashi, Go; Nishizuka, Satoshi] Iwate Med Univ, Dept Surg, Iwate 0208505, Japan. RP Nishizuka, S (reprint author), NCI, Mol Therapeut Program, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM snishizu@iwate-med.ac.jp NR 87 TC 34 Z9 34 U1 1 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0734-9750 EI 1873-1899 J9 BIOTECHNOL ADV JI Biotechnol. Adv. PD JUL-AUG PY 2008 VL 26 IS 4 BP 361 EP 369 DI 10.1016/j.biotechadv.2008.04.002 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 323YG UT WOS:000257483800007 PM 18514460 ER PT J AU Grewal, J Carmichael, SL Ma, C Lammer, EJ Shaw, GM AF Grewal, Jagteshwar Carmichael, Suzan L. Ma, Chen Lammer, Edward J. Shaw, Gary M. TI Maternal periconceptional smoking and alcohol consumption and risk for select congenital anomalies SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article; Proceedings Paper CT 20th Annual Meeting of the Society-for-Pediatric-and-Perinatal-Epidemiologic-Research CY JUN 18-19, 2007 CL Boston, MA SP Soc Pediat & Perinatal Epidemiol Res DE smoking; alcohol; drinking; conotruncal heart defect; NTDs; clefts; congenital anomalies; pregnancy ID PARENTAL CIGARETTE-SMOKING; NEURAL-TUBE DEFECTS; BIRTH-DEFECTS; OROFACIAL CLEFTS; ORAL CLEFTS; SPONTANEOUS-ABORTION; COFFEE CONSUMPTION; PREGNANCY; MALFORMATIONS; HEART AB BACKGROUND: This study examined the association between maternal smoking and alcohol use (including binge drinking) during the periconceptional period (i.e., 2 months before through 2 months after conception) and the risk of orofacial clefts, NTDs, and conotruncal heart defects in offspring. METHODS: Data were drawn from a population-based case-control study of fetuses and live-born infants among a cohort of California births between July 1999 and June 2003. The 1,355 cases comprised of 701 orofacial clefts, 337 NTDs, and 323 conotruncal heart defects. Information on smoking and alcohol consumption was obtained via telephone interviews with mothers of 1,355 (80% of eligibles) cases and 700 (77% of eligibles) nonmalformed, live-born controls. RESULTS: Maternal smoking of five cigarettes or less per day was associated with reduced risks of NTDs (OR 0.7; 95% CI: 0.3, 1.4), whereas the risk associated with higher cigarette consumption was lower for conotruncal heart defects (OR 0.5; 95% CI: 0.2, 1.2). Maternal intake of alcohol less than 1 day per week was associated with a 1.6- to 2.1-fold higher risk of NTDs (95% CI: 0.9, 2.6), d-transposition of the great arteries (95% CI: 1.1, 3.2), and multiple cleft lip with or without cleft palate (CLP) (95% CI: 0.8, 4.5). Risks associated with more frequent alcohol intake were 2.1 for NTDs (95% CI: 1.1, 4.0) and 2.6 for multiple CLP (95% CI: 1.1, 6.1). CONCLUSIONS: This study observed that maternal alcohol intake increased the risk for d-transposition of the great arteries, NTDs, and multiple CLP in infants. By contrast, smoking was associated with a lower risk of NTDs and conotruncal heart defects. C1 [Lammer, Edward J.] Childrens Hosp Oakland, Res Inst, March Dimes Calif Res Div, Oakland, CA 94609 USA. [Grewal, Jagteshwar] NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. [Carmichael, Suzan L.; Ma, Chen; Shaw, Gary M.] March Dimes Calif Res Div, Oakland, CA USA. RP Carmichael, SL (reprint author), Childrens Hosp Oakland, Res Inst, March Dimes Calif Res Div, 5700 Martin Luther King Jr Way, Oakland, CA 94609 USA. EM SCarmichael@marchofdimes.com OI Grewal, Jagteshwar/0000-0002-0141-4876 FU NICHD NIH HHS [R01 HD042538, R01 HD042538-03, R01 HD 42538-03]; PHS HHS [U50/CCU913241] NR 39 TC 82 Z9 84 U1 2 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD JUL PY 2008 VL 82 IS 7 BP 519 EP 526 DI 10.1002/bdra.20461 PG 8 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 329YP UT WOS:000257906800004 PM 18481814 ER PT J AU Rollison, DE Howlader, N Smith, MT Strom, SS Merritt, WD Ries, LA Edwards, BK List, AF AF Rollison, Dana E. Howlader, Nadia Smith, Marlyn T. Strom, Sara S. Merritt, William D. Ries, Lynn A. Edwards, Brenda K. List, Alan F. TI Epidemiology of myelodysplastic syndromes and chronic myeloproliferative disorders in the United States, 2001-2004, using data from the NAACCR and SEER programs SO BLOOD LA English DT Article ID WORLD-HEALTH-ORGANIZATION; FEATURING CANCER; POPULATION; CLASSIFICATION; SURVIVAL; LEUKEMIA; NATION AB Reporting of myelodysplastic syndromes (MDSs) and chronic myeloproliferative disorders (CMDs) to population-based cancer registries in the United States was initiated in 2001. In this first analysis of data from the North American Association of Central Cancer Registries (NAACCR), encompassing 82% of the US population, we evaluated trends in MDS and CMD incidence, estimated case numbers for the entire United States, and assessed trends in diagnostic recognition and reporting. Based on more than 40 000 observations, average annual age-adjusted incidence rates of MDS and CMD for 2001 through 2003 were 3.3 and 2.1 per 100 000, respectively. Incidence rates increased with age for both MDS and CMD (P < .05) and were highest among whites and non-Hispanics. Based on follow-up data through 2004 from the Surveillance, Epidemiology, and End Results (SEER) Program, overall relative 3-year survival rates for MDS and CMD were 45% and 80%, respectively, with males experiencing poorer survival than females. Applying the observed age-specific incidence rates to US Census population estimates, approximately 9700 patients with MDS and 6300 patients with CMD were estimated for the entire United States in 2004. MDS incidence rates significantly increased with calendar year in 2001 through 2004, and only 4% of patients were reported to registries by physicians' offices. Thus, MDS disease burden in the United States may be underestimated. C1 [Rollison, Dana E.] H Lee Moffitt Canc Ctr & Res Inst, Div Canc Prevent & Control, Tampa, FL USA. [Smith, Marlyn T.] Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA. [Strom, Sara S.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Merritt, William D.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Ries, Lynn A.; Edwards, Brenda K.] NCI, Surveillance Res Program, Bethesda, MD 20892 USA. [List, Alan F.] H Lee Moffitt Canc Ctr & Res Inst, Hematol Malignancy Div, Tampa, FL USA. RP Rollison, DE (reprint author), H Lee Moffitt Canc Ctr & Res Inst, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM dana.rollison@moffitt.org NR 20 TC 281 Z9 294 U1 3 U2 8 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 2008 VL 112 IS 1 BP 45 EP 52 DI 10.1182/blood-2008-01-134858 PG 8 WC Hematology SC Hematology GA 319XW UT WOS:000257199300015 PM 18443215 ER PT J AU Nagababu, E Fabry, ME Nagel, RL Rifkind, JM AF Nagababu, Enika Fabry, Mary E. Nagel, Ronald L. Rifkind, Joseph M. TI Heme degradation and oxidative stress in murine models for hemoglobinopathies: Thalassemia, sickle cell disease and hemoglobin C disease SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article DE heme degradation; fluorescence; transgenic mice; sickle cell; thalassemia; hemoglobin ID RED-BLOOD-CELLS; OCCURRING ANTI-BAND-3 ANTIBODIES; HUMAN BETA-S; HYDROGEN-PEROXIDE; MOLECULAR-MECHANISM; LIPID-PEROXIDATION; TRANSGENIC MICE; MOUSE MODEL; AUTOXIDATION; ERYTHROCYTE AB Red blood cells with abnormal hemoglobins (Hb) are frequently associated with increased hemoglobin autoxidation, accumulation of iron in membranes, increased membrane damage and a shorter red cell life span. The mechanisms for many of these changes have not been elucidated. We have shown in our previous studies that hydrogen peroxide formed in association with hemoglobin autoxidation reacts with hemoglobin and initiates a cascade of reactions that results in heme degradation with the formation of two fluorescent emission bands and the release of iron. Heme degradation was assessed by measuring the fluorescent band at ex 321 nm. A 5.6 fold increase in fluorescence was found in red cells from sickle transgenic mice that expressed exclusively human globins when compared to red cells from control mice. When sickle transgenic mice co-express the gamma M transgene, that expresses ME and inhibits polymerization, heme degradation is decreased. Mice expressing exclusively hemoglobin C had a 6.9 fold increase in fluorescence compared to control. Heme degradation was also increased 3.5 fold in beta-thalassemic mice generated by deletion of murine beta(major). Membrane bound IgG and red cell metHb were highly correlated with the intensity of the fluorescent heme degradation band. These results suggest that degradation of the heme moiety in intact hemoglobin and/or degradation of free heme by peroxides are higher in pathological RBCs. Concomitant release of iron appears to be responsible for the membrane damage that leads to IgG binding and the removal of red cells from circulation. Published by Elsevier Inc. C1 [Nagababu, Enika; Rifkind, Joseph M.] NIA, Mol Dynam Sect, NIH, Baltimore, MD 21224 USA. [Fabry, Mary E.; Nagel, Ronald L.] Albert Einstein Coll Med, Dept Med Hematol, Bronx, NY 10461 USA. RP Rifkind, JM (reprint author), NIA, Mol Dynam Sect, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM rifkindj@mail.nih.gov FU Intramural NIH HHS [Z01 AG000047-37, Z99 AG999999] NR 36 TC 28 Z9 29 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD JUL-AUG PY 2008 VL 41 IS 1 BP 60 EP 66 DI 10.1016/j.bcmd.2007.12.003 PG 7 WC Hematology SC Hematology GA 314CF UT WOS:000256785600010 PM 18262448 ER PT J AU Hotchkiss, CE Weis, C Blaydes, B Newbold, R Delclos, KB AF Hotchkiss, Charlotte E. Weis, Connie Blaydes, Betty Newbold, Retha Delclos, K. Barry TI Multigenerational exposure to ethinyl estradiol affects bone geometry, but not bone mineral density in rats SO BONE LA English DT Article DE estrogen; bone development; bone mineral density; endocrine disruptors; rat ID ORAL-CONTRACEPTIVE USE; YOUNG-ADULT WOMEN; EPIGENETIC TRANSGENERATIONAL ACTIONS; DEPOT-MEDROXYPROGESTERONE ACETATE; BIRTH-CONTROL PILLS; 30 MU-G; FEMALE RATS; POSTMENOPAUSAL WOMEN; PHYSICAL-ACTIVITY; GROWING-RATS AB Estrogenic compounds are known to prevent bone loss in ovariectomized adult rats; however, their effects on bone in developing and reproductively-intact rats are less well-understood. In a large multigenerational experiment 0, 2, 10, or 50 ppb ethinyl estradiol (EE) in the diet was fed to intact male and female rats from conception until either weaning, postnatal day 140, or continuously for 2 years. Vertebrae (lumbar and caudal) and femurs were collected from subsets of these animals at necropsy at 48 days, 70 days, 140 days, or 2 years of age and subjected to dual-energy X-ray absorptiometry (DXA) scanning to measure bone mineral density (BMD), bone mineral content (BMC), and bone area. In addition, the length, cross-sectional area, marrow area, and cortical bone area of the femurs were measured directly in all animals at PND 140 and 2 years. Continuous dietary intake of 50 ppb EE decreased body weight by 8-27%. BMD adjusted for body weight was not affected by EE, with the exception of an increase in the caudal vertebrae in males treated with 50 ppb EE. In female rats, continuous treatment with 50 ppb EE decreased length and cross-sectional area of the femur. The length of the femur was decreased in the first two generations following institution of a phytoestrogen-free diet at the initiation of the study in all animals, including controls, but returned to the original length by the third or fourth generation. The cross-sectional area of the femur also varied by generation. In conclusion, a high dose of EE throughout the lifespan resulted in decreased bone size in females, which could reduce the force required to break the bone. Furthermore, dietary changes may have epigenetic effects which persist for multiple generations. (C) 2008 Elsevier Inc. All rights reserved. C1 [Hotchkiss, Charlotte E.; Weis, Connie; Blaydes, Betty; Delclos, K. Barry] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Newbold, Retha] Natl Inst Environm Hlth Sci, Mol Toxicol Lab, Res Triangle Pk, NC USA. RP Hotchkiss, CE (reprint author), Univ Washington, Washington Natl Primate Res Ctr, Box 357330, Seattle, WA 98195 USA. EM chotchki@wanprc.org NR 89 TC 5 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 EI 1873-2763 J9 BONE JI Bone PD JUL PY 2008 VL 43 IS 1 BP 110 EP 118 DI 10.1016/j.bone.2008.03.016 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 319GC UT WOS:000257151100014 PM 18467201 ER PT J AU Dubois-Dalcq, M Williams, A Stadelmann, C Stankoff, B Zalc, B Lubetzki, C AF Dubois-Dalcq, Monique Williams, Anna Stadelmann, Christine Stankoff, Bruno Zalc, Bernard Lubetzki, Catherine TI From fish to man: understanding endogenous remyelination in central nervous system demyelinating diseases SO BRAIN LA English DT Review DE multiple sclerosis; nodes of Ranvier; enhancing repair; animal models; transparent fish ID MULTIPLE-SCLEROSIS PATIENTS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; OLIGODENDROCYTE PRECURSOR CELLS; LEUKEMIA INHIBITORY FACTOR; MYELIN BASIC-PROTEIN; NEURAL STEM-CELLS; SPINAL-CORD AXONS; WHITE-MATTER; SCHWANN-CELLS; MAGNETIZATION-TRANSFER AB In the central nervous system (CNS) of man, evolutionary pressure has preserved some capability for remyelination while axonal regeneration is very limited. In contrast, two efficient programmes of regeneration exist in the adult fish CNS, neurite regrowth and remyelination. The rapidity of CNS remyelination is critical since it not only restores fast conduction of nerve impulses but also maintains axon integrity. If myelin repair fails, axons degenerate, leading to increased disability. In the human CNS demyelinating disease multiple sclerosis (MS), remyelination often takes place in the midst of inflammation. Here, we discuss recent studies that address the innate repair capabilities of the axon-glia unit from fish to man. We propose that expansion of this research field will help find ways to maintain or enhance spontaneous remyelination in man. C1 [Dubois-Dalcq, Monique] NINDS, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. [Williams, Anna] Western Gen Hosp, Dept Clin Neurosci, Edinburgh EH4 2XU, Midlothian, Scotland. [Stadelmann, Christine] Univ Gottingen, Med Ctr, Inst Neuropathol, D-37075 Gottingen, Germany. [Stankoff, Bruno; Zalc, Bernard; Lubetzki, Catherine] Univ Paris 06, INSERM, U711, F-75013 Paris, France. [Stankoff, Bruno; Zalc, Bernard; Lubetzki, Catherine] Univ Paris 06, Fac Med, IFR 70, F-75252 Paris 05, France. [Stankoff, Bruno; Zalc, Bernard; Lubetzki, Catherine] Hop La Pitie Salpetriere, AP HP, F-75013 Paris, France. RP Dubois-Dalcq, M (reprint author), NINDS, Porter Neurosci Res Ctr, NIH, Bdg 35,Pod 2A106,35 Convent Dr MSC3706, Bethesda, MD 20892 USA. EM mdalcq@pasteur.fr FU Intramural NIH HHS [Z99 NS999999] NR 161 TC 46 Z9 47 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JUL PY 2008 VL 131 BP 1686 EP 1700 DI 10.1093/brain/awn076 PN 7 PG 15 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 322TB UT WOS:000257397100004 PM 18474520 ER PT J AU Mittelbronn, M Sullivan, T Stewart, CL Bornemann, A AF Mittelbronn, Michel Sullivan, Teresa Stewart, Colin L. Bornemann, Antje TI Myonuclear degeneration in LMNA null mice SO BRAIN PATHOLOGY LA English DT Article DE Electron microscopy; myotendinous junction; nucleo-cytoskeletal integrity ID DREIFUSS MUSCULAR-DYSTROPHY; LAMINOPATHIES; NUCLEI; EXPRESSION; INTEGRITY; EDMD AB Lamins A/C, the major constituent of the nuclear lamina, confer mechanical stability to nuclei. We examined the myonuclei of LMNA null mice at the myotendinous junctions (MTJ), the site of longitudinal force transmission from contractile proteins to extracellular proteins. The right soleus and rectus femoris muscles of five null mutants aged 5-7 weeks and two wild-type animals aged 5 weeks and 6 months were examined by electron microscopy. The myofibers merging into the tendons were assessed for nuclear disintegration and cytoplasmic degeneration. The myofibers of the wild-type rectus femoris and soleus muscles revealed 19-27 nuclei/50 myofibers and 5-8/20, respectively, with no signs of degeneration. The rectus femoris muscle fibers of the null mice contained 75-117 myonuclei/50 myofibers, the soleus muscle, 13-36 nuclei/20 myofibers. Eleven to twenty-one per 50 myonuclei of the rectus femoris myonuclei showed chromatin clumping, nuclear fragmentation, nuclear inclusions and invaginations, and intranuclear filaments. The values were 12-19/50 for the soleus myonuclei. Moreover, 5-12/50 rectus femoris myofibers and 5-14/20, of the soleus myofibers showed cytoplasmic degeneration. None of these changes was found distal to the MTJ. These results favor the notion that myonuclei lacking a functional lamina are susceptible to mechanical stress in vivo. These alterations may contribute to the development of early joint contractures, a feature of ADEDMD. C1 [Mittelbronn, Michel; Bornemann, Antje] Univ Tubingen, Inst Brain Res, D-72076 Tubingen, Germany. [Mittelbronn, Michel] Univ Zurich Hosp, Inst Neuropathol, Zurich, Switzerland. [Sullivan, Teresa; Stewart, Colin L.] NCI, Canc & Dev Biol Lab, Frederick Canc Res & Dev Ctr, Bethesda, MD 20892 USA. RP Bornemann, A (reprint author), Univ Tubingen, Inst Brain Res, Calwerstr 3, D-72076 Tubingen, Germany. EM antje.bornemann@med.uni-tuebingen.de NR 13 TC 10 Z9 10 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD JUL PY 2008 VL 18 IS 3 BP 338 EP 343 DI 10.1111/j.1750-3639.2008.00123.x PG 6 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 308MU UT WOS:000256395500004 PM 18371185 ER PT J AU Paulus, W Classen, J Cohen, LG Large, CH Di Lazzaro, V Nitsche, M Pascual-Leone, A Rosenow, F Rothwell, JC Ziemann, U AF Paulus, Walter Classen, Joseph Cohen, Leonardo G. Large, Charles H. Di Lazzaro, Vincenzo Nitsche, Michael Pascual-Leone, Alvaro Rosenow, F. Rothwell, John C. Ziemann, Ulf TI State of the art: Pharmacologic effects on cortical excitability measures tested by transcranial magnetic stimulation SO BRAIN STIMULATION LA English DT Review DE transcranial magnetic stimulation; TMS; pharmacology; ICI; ICF; silent period; SAI ID HUMAN MOTOR CORTEX; I-WAVE INTERACTION; NOREPINEPHRINE-REUPTAKE INHIBITOR; HUMAN CORTICOSPINAL EXCITABILITY; LATENCY AFFERENT INHIBITION; SILENT PERIOD; INTRACORTICAL INHIBITION; CONSCIOUS HUMANS; BRAIN-STIMULATION; GABA(B) RECEPTOR AB The combination of brain stimulation techniques like transcranial magnetic stimulation (TMS) with CNS active drugs in humans now offers a unique opportunity to explore the physiologic effects of these substances in vivo in the human brain. Motor threshold, motor evoked potential size, motor evoked potential intensity curves, cortical silent period, short-interval intracortical inhibition, intracortical facilitation, short-interval intracortical facilitation, long-interval intracortical inhibition and short latency afferent inhibition represent the repertoire for investigating drug effects on motor cortical excitability by TMS. Here we present an updated overview on the pharmacophysiologic mechanisms with special emphasis on methodologic pitfalls and possible future developments or requirements. (c) 2008 Elsevier Inc. All rights reserved. C1 [Paulus, Walter; Nitsche, Michael] Univ Gottingen, Dept Clin Neurophysiol, Gottingen, Germany. [Classen, Joseph] Univ Wurzburg, Dept Neurol, Wurzburg, Germany. [Cohen, Leonardo G.] NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. [Cohen, Leonardo G.] NINDS, Stroke Neurorehabil Clin, NIH, Bethesda, MD 20892 USA. [Large, Charles H.] Glaxo Smith Kline SpA, Med Res Ctr, Verona, Italy. [Di Lazzaro, Vincenzo] Univ Cattolica Sacro Cuore, Inst Neurol, Rome, Italy. [Pascual-Leone, Alvaro] Harvard Univ, Sch Med, Berenson Allen Ctr Noninvas Brain Stimulat, Boston, MA USA. [Pascual-Leone, Alvaro] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Rosenow, F.] Univ Marburg, Dept Neurol, Marburg, Germany. [Rothwell, John C.] Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, London WC1N 3BG, England. [Ziemann, Ulf] Univ Frankfurt, Dept Neurol, Frankfurt, Germany. RP Paulus, W (reprint author), Univ Gottingen, Dept Clin Neurophysiol, Gottingen, Germany. RI Nitsche, Michael/B-6755-2012; Paulus, Walter/A-3544-2009; OI Paulus, Walter/0000-0001-5549-8377; Rothwell, John/0000-0003-1367-6467; Di Lazzaro, Vincenzo/0000-0002-9113-5925 NR 126 TC 164 Z9 164 U1 2 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1935-861X J9 BRAIN STIMUL JI Brain Stimul. PD JUL PY 2008 VL 1 IS 3 BP 151 EP 163 DI 10.1016/j.brs.2008.06.002 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 398FA UT WOS:000262716800004 PM 20633382 ER PT J AU Ziemann, U Paulus, W Nitsche, MA Pascual-Leone, A Byblow, WD Berardelli, A Siebner, HR Classen, J Cohen, LG Rothwell, JC AF Ziemann, Ulf Paulus, Walter Nitsche, Michael A. Pascual-Leone, Alvaro Byblow, Winston D. Berardelli, Alfredo Siebner, Hartwig R. Classen, Joseph Cohen, Leonardo G. Rothwell, John C. TI Consensus: Motor cortex plasticity protocols SO BRAIN STIMULATION LA English DT Review DE transcranial magnetic stimulation; transcranial direct current stimulation; paired associative stimulation; theta burst stimulation; human motor cortex ID TRANSCRANIAL MAGNETIC STIMULATION; PAIRED-ASSOCIATIVE STIMULATION; THETA-BURST-STIMULATION; LOW-FREQUENCY RTMS; NONINVASIVE BRAIN-STIMULATION; LONG-TERM POTENTIATION; HZ REPETITIVE TMS; SOMATOSENSORY-EVOKED POTENTIALS; LEVODOPA-INDUCED DYSKINESIAS; TIMING-DEPENDENT PLASTICITY AB Noninvasive transcranial stimulation is being increasingly used by clinicians and neuroscientists to alter deliberately the status of the human brain. Important applications are the induction of virtual lesions (for example, transient dysfunction) to identify the importance of the stimulated brain network for a certain sensorimotor or cognitive task, and the induction of changes in neuronal excitability, synaptic plasticity or behavioral function Outlasting the Stimulation. for example, for therapeutic purposes. The aim of this article is to review critically the properties of the different currently used stimulation protocols. including a focus On their particular strengths and weaknesses, to facilitate their appropriate and conscientious application. (c) 2008 Elsevier Inc. All rights reserved. C1 [Ziemann, Ulf] Goethe Univ Frankfurt, Dept Neurol, D-60528 Frankfurt, Germany. [Paulus, Walter; Nitsche, Michael A.] Univ Gottingen, Dept Clin Neurophysiol, D-3400 Gottingen, Germany. [Pascual-Leone, Alvaro] Beth Israel Deaconess Med Ctr, Berebson Allen Ctr Noninvas Brain Stimulat, Boston, MA 02215 USA. [Pascual-Leone, Alvaro] Harvard Univ, Sch Med, Boston, MA USA. [Byblow, Winston D.] Univ Auckland, Movement Neurosci Lab, Auckland 1, New Zealand. [Berardelli, Alfredo] Univ Roma La Sapienza, Neuromed Inst, Dept Neurol Sci, Rome, Italy. [Siebner, Hartwig R.] Univ Kiel, Dept Neurol, D-2300 Kiel, Germany. [Classen, Joseph] Univ Wurzburg, Dept Neurol, D-8700 Wurzburg, Germany. [Cohen, Leonardo G.] NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. [Rothwell, John C.] Inst Neurol, Sobell Dept, London WC1N 3BG, England. RP Ziemann, U (reprint author), Goethe Univ Frankfurt, Dept Neurol, Schleusenweg 2-16, D-60528 Frankfurt, Germany. EM u.ziemann@em.uni-frankfurt.de RI Byblow, Winston/D-3579-2009; Nitsche, Michael/B-6755-2012; Siebner, Hartwig/G-4052-2016; Paulus, Walter/A-3544-2009; OI Paulus, Walter/0000-0001-5549-8377; Rothwell, John/0000-0003-1367-6467 NR 197 TC 231 Z9 235 U1 1 U2 24 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1935-861X EI 1876-4754 J9 BRAIN STIMUL JI Brain Stimul. PD JUL PY 2008 VL 1 IS 3 SI SI BP 164 EP 182 DI 10.1016/j.brs.2008.06.006 PG 19 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 398FA UT WOS:000262716800005 PM 20633383 ER PT J AU Nitsche, MA Cohen, LG Wassermann, EM Priori, A Lang, N Antal, A Paulus, W Hummel, F Boggio, PS Fregni, F Pascual-Leone, A AF Nitsche, Michael A. Cohen, Leonardo G. Wassermann, Eric M. Priori, Alberto Lang, Nicolas Antal, Andrea Paulus, Walter Hummel, Friedhelm Boggio, Paulo S. Fregni, Felipe Pascual-Leone, Alvaro TI Transcranial direct current stimulation: State of the art 2008 SO BRAIN STIMULATION LA English DT Review DE tDCS; brain; human; neuroplasticity ID HUMAN MOTOR CORTEX; NONINVASIVE CORTICAL STIMULATION; DORSOLATERAL PREFRONTAL CORTEX; DC BRAIN POLARIZATION; PRIMARY VISUAL-CORTEX; WORKING-MEMORY; MAGNETIC STIMULATION; EXCITABILITY CHANGES; EVOKED-POTENTIALS; MAJOR DEPRESSION AB Effects of weak electrical currents oil brain and neuronal function were first described decades ago. Recently. DC polarization of the brain was reintroduced as a noninvasive technique to alter cortical activity in humans. Beyond this, transcranial direct current stimulation (tDCS) of different cortical areas has been shown, ill various Studies. to result in modifications of perceptual. cognitive, and behavioral functions. Moreover, preliminary data suggest that it can induce beneficial effects in brain disorders. Brain stimulation with weak direct Currents is a promising tool in human neuroscience and neurobehavioral research. To facilitate and standardize future tDCS Studies, we offer this overview of the state of the art for tDCS. (c) 2008 Elsevier Inc. All rights reserved. C1 [Nitsche, Michael A.; Antal, Andrea; Paulus, Walter] Univ Gottingen, Dept Clin Neurophysiol, D-37075 Gottingen, Germany. [Cohen, Leonardo G.] NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. [Cohen, Leonardo G.] NINDS, Stroke Neurorehabil Clin, NIH, Bethesda, MD 20892 USA. [Wassermann, Eric M.] NINDS, Brain Stimulat Unit, NIH, Bethesda, MD 20892 USA. [Priori, Alberto] Univ Milan, Osped Maggiore Policlin, Fdn IRCCS, Dipartimento Sci Neurol, Milan, Italy. [Lang, Nicolas] Univ Kiel, Dept Neurol, D-2300 Kiel, Germany. [Hummel, Friedhelm] Univ Hamburg, Dept Neurol, Hamburg, Germany. [Boggio, Paulo S.] Univ Prebiteriana Mackenzie, Dept Neurosci & Behavior, Sao Paulo, Brazil. [Boggio, Paulo S.] Univ Prebiteriana Mackenzie, Pervas Dev Disorder Program, Sao Paulo, Brazil. [Fregni, Felipe; Pascual-Leone, Alvaro] Harvard Univ, Sch Med, Berenson Allen Ctr Noninvas Brain Stimulat, Boston, MA USA. [Fregni, Felipe; Pascual-Leone, Alvaro] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Nitsche, MA (reprint author), Univ Gottingen, Dept Clin Neurophysiol, Robert Koch St 40, D-37075 Gottingen, Germany. EM mnitsch1@gwdg.de RI Nitsche, Michael/B-6755-2012; Boggio, Paulo/K-6272-2012; Lang, Nicolas/A-5034-2009; Paulus, Walter/A-3544-2009 OI Boggio, Paulo/0000-0002-6109-0447; Lang, Nicolas/0000-0002-0950-7727; Paulus, Walter/0000-0001-5549-8377 NR 121 TC 845 Z9 871 U1 16 U2 201 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1935-861X J9 BRAIN STIMUL JI Brain Stimul. PD JUL PY 2008 VL 1 IS 3 BP 206 EP 223 DI 10.1016/j.brs.2008.06.004 PG 18 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 398FA UT WOS:000262716800008 PM 20633386 ER PT J AU Lavigne, JA Takahashi, Y Chandramouli, GVR Liu, HT Perkins, SN Hursting, SD Wang, TTY AF Lavigne, Jackie A. Takahashi, Yoko Chandramouli, Gadisetti V. R. Liu, Huaitian Perkins, Susan N. Hursting, Stephen D. Wang, Thomas T. Y. TI Concentration-dependent effects of genistein on global gene expression in MCF-7 breast cancer cells: an oligo microarray study SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE genistein; isoflavone; microarray; phytochemical; breast cancer ID TUMOR-NECROSIS-FACTOR; SOY ISOFLAVONE GENISTEIN; MOLECULAR-CLONING; INTERLEUKIN-1 FAMILY; DNA MICROARRAY; BCL-2 FAMILY; KAPPA-B; RECEPTOR; ESTROGEN; PROTEIN AB Breast cancer is the most commonly diagnosed cancer among US women; there is therefore great interest in developing preventive and treatment strategies for this disease. Because breast cancer incidence is much lower in countries where women consume high levels of soy, bioactive compounds in this food source have been studied for their effects on breast cancer. Genistein, found at high levels in soybeans and soy foods, is a controversial candidate breast cancer preventive phytochemical whose effects on breast cells are complex. To understand more clearly the molecular mechanisms underlying the effects of genistein on breast cancer cells, we used a DNA oligo microarray approach to examine the global gene expression patterns in MCF-7 breast cancer cells at both physiologic (1 or 5 mu M) and pharmacologic (25 mu M) genistein concentrations. Microarray analyses were performed on MCF-7 cells after 48 h of either vehicle or 1, 5, or 25 mu M genistein treatment. We found that genistein altered the expression of genes belonging to a wide range of pathways, including estrogen- and p53-mediated pathways. At 1 and 5 mu M, genistein elicited an expression pattern suggestive of increased mitogenic activity, confirming the proliferative response to genistein observed in cultured MCF-7 cells, while at 25 mu M genistein effected a pattern that likely contributes to increased apoptosis, decreased proliferation and decreased total cell number, also consistent with cell culture results. These findings provide evidence for a molecular signature of genistein's effects in MCF-7 cells and lay the foundation for elucidating the mechanisms of genistein's biological impact in breast cancer cells. C1 [Lavigne, Jackie A.] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Takahashi, Yoko] Phytonutr Lab, Beltsville, MD USA. [Takahashi, Yoko] ARS, Beltsville Human Nutr Res Ctr, USDA, Natl Food Res Inst, Tsukuba, Ibaraki, Japan. [Liu, Huaitian] NCI, Ctr Bioinformat SAIC, NIH, Bethesda, MD USA. [Perkins, Susan N.; Hursting, Stephen D.] Univ Texas Austin, Div Nutr Sci, Austin, TX 78712 USA. [Wang, Thomas T. Y.] Agr Res Serv, Phytonutr Lab, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD 20705 USA. RP Wang, TTY (reprint author), Agr Res Serv, Phytonutr Lab, Beltsville Human Nutr Res Ctr, USDA, Bldg 307C,Room 132, Beltsville, MD 20705 USA. EM tom.wang@ars.usda.gov NR 85 TC 26 Z9 29 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUL PY 2008 VL 110 IS 1 BP 85 EP 98 DI 10.1007/s10549-007-9705-6 PG 14 WC Oncology SC Oncology GA 309OV UT WOS:000256471000008 PM 17687646 ER PT J AU Han, SH Lee, KM Choi, JY Park, SK Lee, JY Lee, JE Noh, DY Ahn, SH Han, WS Kim, DH Hong, YC Ha, E Yoo, KY Kang, DH AF Han, Sohee Lee, Kyoung-Mu Choi, Ji-Yeob Park, Sue Kyung Lee, Ji-Young Lee, Jong Eun Noh, Dong-Young Ahn, Sei-Hyun Han, Wonshik Kim, Dong-Hyun Hong, Yun-Chul Ha, Eunhee Yoo, Keun-Young Kang, Daehee TI CASP8 polymorphisms, estrogen and progesterone receptor status, and breast cancer risk SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast cancer; CASP8; estrogen receptor; polymorphism; progesterone receptor ID APOPTOSIS; VARIANT; GENE; ASSOCIATION AB Objectives This study was conducted to evaluate the potential role of CASP8 genetic polymorphisms in the etiology of breast cancer in a case-control study, Korea. Methods Incident breast cancer cases confirmed histologically (n = 1,599) were recruited from two hospitals in Seoul during 2001-2005. Control subjects (n = 1,536) were selected from the Health Examinee Cohort from Seoul and Gyeonggi Province surrounding Seoul, Korea. Three SNPs (D302H D > H, 5'-UTR C > T, and K337K G > A) were genotyped by the primer extension assay. The CASP8 D302H, which was not polymorphic in 48 samples, was excluded in further genotyping. Odds ratios and 95% confidential intervals (95% CIs) were estimated by unconditional logistic regression model adjusted for age at enrollment, education, age at first full-term pregnancy, cigarette smoking, and family history of breast cancer. Results The 5'-UTR T allele containing genotypes (CT/TT) were associated with an increased risk of breast cancer, compared with those with the CC genotype (OR = 1.13, 95% CI = 0.95-1.34; and OR = 1.48, 95% CI = 1.04-2.10, respectively; P-trend = 0.02). When stratified by the estrogen and progesterone receptor status, the association between the 5'-UTR T allele and breast cancer risk was prominent in ER(+) and PR(+) cases among pre-menopausal women (OR = 1.31, 95% CI = 1.00-1.72 and OR = 1.40, 95% CI = 1.06-1.85, respectively), whereas the association was found prominent in ER(-) or PR(-) cases (OR = 1.32, 95% CI = 0.93-1.87 and OR = 1.42, 95% CI = 1.04-1.94, respectively) among post-menopausal women. Conclusion Our results thus suggest that the CASP8 5'-UTR C > T are associated with breast cancer risks and the effect may be modified by estrogen and progesterone receptor status. C1 [Han, Sohee; Park, Sue Kyung; Lee, Ji-Young; Hong, Yun-Chul; Yoo, Keun-Young; Kang, Daehee] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea. [Lee, Kyoung-Mu] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Choi, Ji-Yeob] Roswell Pk Canc Inst, Dept Epidemiol, Buffalo, NY 14263 USA. [Lee, Jong Eun] DNA Link Inc, Seoul, South Korea. [Noh, Dong-Young; Han, Wonshik] Seoul Natl Univ, Coll Med, Dept Surg, Seoul, South Korea. [Ahn, Sei-Hyun] Univ Ulsan, Coll Med, Dept Surg, Seoul, South Korea. [Kim, Dong-Hyun] Hallym Univ, Coll Med, Dept Social & Prevent Med, Chunchon, Kangwon Do, South Korea. [Ha, Eunhee] Ewha Womans Univ, Dept Prevent Med, Seoul, South Korea. [Yoo, Keun-Young] Korea Natl Canc Ctr, Goyang, Gyeonggi Do, South Korea. [Kang, Daehee] Seoul Natl Univ, Canc Res Inst, Seoul, South Korea. RP Kang, DH (reprint author), Seoul Natl Univ, Coll Med, Dept Prevent Med, 28 Yongon Dong, Seoul, South Korea. EM dhkang@snu.ac.kr RI Noh, Dong-Young/G-5531-2011; Choi, Ji-Yeob/J-2796-2012; Hong, Yun-Chul/J-5725-2012; Kang, Dae Hee/E-8631-2012; Yoo, Keun-Young/J-5548-2012; Park, Sue Kyung/J-2757-2012; Han, Wonshik/B-3699-2008 NR 19 TC 15 Z9 15 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUL PY 2008 VL 110 IS 2 BP 387 EP 393 DI 10.1007/s10549-007-9730-5 PG 7 WC Oncology SC Oncology GA 309OW UT WOS:000256471100021 PM 17940865 ER PT J AU Dores, GM Matsuno, RK Weisenburger, DD Rosenberg, PS Anderson, WF AF Dores, Graca M. Matsuno, Rayna K. Weisenburger, Dennis D. Rosenberg, Philip S. Anderson, William F. TI Hairy cell leukaemia: a heterogeneous disease? SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE hairy cell leukaemia; chronic leukaemia; epidemiology; lymphoid malignancy; malignant haematology ID HODGKINS-DISEASE; BREAST-CANCER; UNITED-STATES; RISK-FACTORS; DESCRIPTIVE EPIDEMIOLOGY; INCIDENCE-PATTERNS; AGE INTERACTIONS; VARIANT FORM; LYMPHOMA; RATES AB The US National Cancer Institute's Surveillance, Epidemiology and End Results program was used to develop aetiological clues for hairy cell leukaemia (HCL). Descriptive techniques (age-adjusted incidence trends, age-specific incidence rates (IR), and age distributions-at-diagnosis) were supplemented with mathematical models (two-component mixture, generalized linear regression, and age-period-cohort). There were 2856 cases of HCL diagnosed during 1978-2004 (IR 0.32/100 000 person-years). IRs were nearly 4-fold greater among men than women and more than 3-fold higher for Whites than Blacks. Temporal trends were stable over time. Age-specific IRs increased rapidly until approximately 40 years then rose at a slower pace. The age-specific IR curves reflected bimodal early- and late-onset age distributions-at-diagnosis (or density plots), with some variation by gender. Among both men and women, a two-component mixture model fitted the data better than a single density or cancer population. Age-period-cohort models confirmed statistically significant age-related effects after full adjustment for temporal trends (calendar-period and birth-cohort effects). In summary, age incidence patterns (rates and bimodal densities) suggested that HCL is a heterogeneous disease, consisting of at least two underlying subgroups and/or cancer populations by age-at-onset. Distinct early- and late-onset HCL populations may reflect different age-related causal pathways, risk factor profiles, and/or stem cells of origin. C1 [Dores, Graca M.] Dept Vet Affairs Med Ctr, Med Serv 111, Oklahoma City, OK 73104 USA. [Dores, Graca M.; Matsuno, Rayna K.; Rosenberg, Philip S.; Anderson, William F.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Weisenburger, Dennis D.] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA. RP Dores, GM (reprint author), Dept Vet Affairs Med Ctr, Med Serv 111, 921 N E 13th St, Oklahoma City, OK 73104 USA. EM doresg@mail.nih.gov FU Intramural NIH HHS [ZIA CP010170-13] NR 46 TC 12 Z9 13 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 2008 VL 142 IS 1 BP 45 EP 51 DI 10.1111/j.1365-2141.2008.07156.x PG 7 WC Hematology SC Hematology GA 309EA UT WOS:000256442300005 PM 18477040 ER PT J AU Schubert, J Hillmen, P Roth, A Young, NS Elebute, MO Szer, J Gianfaldoni, G Socie, G Browne, P Geller, R Rother, RP Muus, P AF Schubert, Joerg Hillmen, Peter Roeth, Alexander Young, Neal S. Elebute, Modupe O. Szer, Jeffery Gianfaldoni, Giacomo Socie, Gerard Browne, Paul Geller, Robert Rother, Russel P. Muus, Petra TI Eculizumab, a terminal complement inhibitor, improves anaemia in patients with paroxysmal nocturnal haemoglobinuria SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE paroxysmal nocturnal haemoglobinuria; haemoglobin; haemolysis; transfusion ID PIG-A GENE; FLOW-CYTOMETRY; MONOCLONAL-ANTIBODIES; DIAGNOSIS; PNH; DEFICIENCY; FATIGUE AB In paroxysmal nocturnal haemoglobinuria (PNH), chronic destruction of PNH red blood cells (RBCs) by complement leads to anaemia and other serious morbidities. Eculizumab inhibits terminal complement-mediated PNH RBC destruction by targeting C5. In the phase III, double-blind, placebo-controlled, TRIUMPH study, eculizumab reduced haemolysis, stabilized haemoglobin levels, reduced transfusion requirements and improved fatigue in patients with PNH. Herein, we explored the effects of eculizumab on measures of anaemia in patients from the TRIUMPH study and the open-label SHEPHERD study, a more heterogeneous population. Eculizumab reduced haemolysis regardless of pretreatment transfusion requirements and regardless of whether or not patients became transfusion-dependent during treatment (P < 0.001). Reduction in haemolysis was associated with increased PNH RBC counts (P < 0.001) while reticulocyte counts remained elevated. Eculizumab-treated patients demonstrated significantly higher levels of haemoglobin as compared with placebo in TRIUMPH and relative to baseline levels in SHEPHERD (P < 0.001 for each study). Eculizumab lowered transfusion requirement across multiple pretreatment transfusion strata and eliminated transfusion support in a majority of both TRIUMPH and SHEPHERD patients (P < 0.001). Patients who required some transfusion support during treatment with eculizumab showed a reduction in haemolysis and transfusion requirements and an improvement in fatigue. Eculizumab reduces haemolysis and improves anaemia and fatigue, regardless of transfusion requirements. C1 [Schubert, Joerg] Univ Saarland, Sch Med, D-66421 Homburg, Germany. [Hillmen, Peter] St Jamess Inst Oncol, Dept Haematol, Leeds, W Yorkshire, England. [Roeth, Alexander] Univ Hosp Essen, Dept Haematol, Essen, Germany. [Young, Neal S.] NHLBI, Cell Biol Sect, Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. [Elebute, Modupe O.] Univ London St Georges Hosp, Dept Cellular & Mol Med, London, England. [Szer, Jeffery] Royal Melbourne Hosp, Dept Clin Haematol, Melbourne, Australia. [Gianfaldoni, Giacomo] Univ Careggi, Azienda Osped, Dept Haematol, Florence, Italy. [Socie, Gerard] Hosp St Louis, Serv Hematol, Paris, France. [Socie, Gerard] INSERM, Paris, France. [Browne, Paul] St James Hosp, Dept Haematol, Dublin 8, Ireland. [Geller, Robert; Rother, Russel P.] Alezion Pharmaceut Inc, Cheshire, CT USA. [Muus, Petra] Radboud Univ Nijmegen, Dept Haematol, NL-6525 ED Nijmegen, Netherlands. RP Schubert, J (reprint author), Univ Saarland, Sch Med, D-66421 Homburg, Germany. EM injsch@uks.eu RI Wahlin, Anders/F-6043-2013; Muus, P./L-4539-2015; OI Wahlin, Anders/0000-0001-6402-0463; Browne, Paul/0000-0001-5310-1487; Szer, Jeff/0000-0001-6783-2301 NR 24 TC 22 Z9 24 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 2008 VL 142 IS 2 BP 263 EP 272 DI 10.1111/j.1365-2141.2008.07183.x PG 10 WC Hematology SC Hematology GA 324WO UT WOS:000257550300012 PM 18503589 ER PT J AU Zhao, R Zhang, XY Yang, J Weng, CC Jiang, LL Zhang, JW Shu, XQ Ji, YH AF Zhao, R. Zhang, X-Y Yang, J. Weng, C-C Jiang, L-L Zhang, J-W Shu, X-Q Ji, Y-H TI Anticonvulsant effect of BmK IT2, a sodium channel-specific neurotoxin, in rat models of epilepsy SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE BmK IT2; intrahippocampal injection; status epilepticus; epileptic seizures; sodium channels ID BUTHUS-MARTENSI KARSCH; TEMPORAL-LOBE EPILEPSY; C-FOS EXPRESSION; STATUS EPILEPTICUS; SCORPION NEUROTOXIN; ANTIEPILEPTIC DRUGS; INDUCED SEIZURES; NERVOUS-SYSTEM; ANIMAL-MODELS; IN-VITRO AB Background and purpose: The sodium channel is a primary target for treating central nervous system disorders such as epilepsy. In this study the anticonvulsant effect of BmK IT2, a sodium channel-specific neurotoxin, was evaluated in different animal models of epilepsy. Experimental approach: Experiments were performed on freely moving rats made epileptic by administration of either pentylenetetrazole (PTZ) or pilocarpine. BmK IT2 (0.05-0.5 mu g in 2 mu l) was microinjected into the CA1 area and its effects on PTZ-induced widespread, seizure-like behaviour and cortex epileptiform EEG, as well as on pilocarpine-induced seizure-like behaviour and c-Fos expression were studied. Key results: Intrahippocampal application of BmK IT2 dose-dependently inhibited PTZ-induced seizure-like behaviour, and reduced the numbers and duration of the high amplitude and frequency discharges (HAFDs) of the epileptiform EEG component induced by PTZ. Similarly, in the pilocarpine-induced status epilepticus (SE) model, BmK IT2 significantly prolonged the latency to onset of the SE, reduced the severity of SE and suppressed hippocampal c-Fos expression during SE. Conclusions and implications: BmK IT2 showed anticonvulsant activity as it inhibited the widespread seizures induced by PTZ and pilocarpine-induced SE in rats. This activity might be due to the modulation of sodium channels in the hippocampus. Hence, BmK IT2 could be used as a novel tool to explore the molecular and pathological mechanisms of epilepsy with regard to the involvement of sodium channels. C1 [Yang, J.; Weng, C-C; Jiang, L-L; Zhang, J-W; Shu, X-Q; Ji, Y-H] Shanghai Univ, Sch Life Sci, Shanghai 200444, Peoples R China. [Zhao, R.] Chinese Acad Sci, Grad Sch, Inst Phys, Shanghai Inst Biol Sci, Shanghai, Peoples R China. [Zhang, X-Y] Natl Inst Environm Hlth Sci, Membrane Signaling Grp, Neurobiol Lab, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. RP Ji, YH (reprint author), Shanghai Univ, Sch Life Sci, Shang Da Rd 99, Shanghai 200444, Peoples R China. EM yhji@staff.shu.edu.cn RI Zhao, Rong/O-1829-2013; Ji, Yonghua/B-7769-2014 NR 53 TC 12 Z9 14 U1 0 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD JUL PY 2008 VL 154 IS 5 BP 1116 EP 1124 DI 10.1038/bjp.2008.156 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 320XV UT WOS:000257269400021 PM 18587450 ER PT J AU Conde-Agudelo, A Lindheimer, M AF Conde-Agudelo, Agustin Lindheimer, Marshall TI Use of Doppler ultrasonography to predict pre-eclampsia SO CANADIAN MEDICAL ASSOCIATION JOURNAL LA English DT Letter ID SYSTEMATIC REVIEWS; TESTS C1 [Conde-Agudelo, Agustin] NICHHD, Perinatol Res Branch, Intramural Div, NIH, Bethesda, MD 20892 USA. [Lindheimer, Marshall] Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. [Lindheimer, Marshall] Univ Chicago, Dept Med, Chicago, IL 60637 USA. RP Conde-Agudelo, A (reprint author), NICHHD, Perinatol Res Branch, Intramural Div, NIH, Bethesda, MD 20892 USA. NR 6 TC 5 Z9 5 U1 0 U2 1 PU CMA-CANADIAN MEDICAL ASSOC PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 3Y6, CANADA SN 0820-3946 J9 CAN MED ASSOC J JI Can. Med. Assoc. J. PD JUL 1 PY 2008 VL 179 IS 1 BP 53 EP 53 DI 10.1503/cmaj.1080039 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 315RU UT WOS:000256897900020 PM 18591529 ER PT J AU Wang, WX Figg, WD AF Wang, Weixin Figg, William D. TI Secondary BRCA1 and BRCA2 alterations and acquired chemoresistance SO CANCER BIOLOGY & THERAPY LA English DT Article DE BRCA1; BRCA2; resistance; mutation; PARP; cisplatin; inhibitor ID NUCLEOTIDE EXCISION-REPAIR; MISMATCH REPAIR; RESISTANCE; CISPLATIN; MUTATIONS; CANCER; CELLS; CARCINOMAS; POLYMERASE; INHIBITORS AB Tumor suppressor BRCA1 and BRCA2 are frequently mutated in familial breast and ovarian cancer. More than ten percent of women with breast or ovarian cancer carry BRCA1 or BRCA2 (BRCA1/2) mutations. Cancers that arise in mutation carriers have often lost the wild-type allele through somatic alterations during tumor progression. BRCA1/2 play important roles in homologous recombination repair of DNA double-strand breaks. Because of this, BRCA1/2-deficient cancers often have a better response to DNA cross-linking agents such as platinum analogues and to poly(ADPribose) polymerase (PARP) inhibitors. However, over time, the majority of these BRCA1/2-deficient cancers become resistant and patients die from refractory diseases. Three recent studies demonstrated that acquired resistance to platinum analogues or PARP inhibitors in tumors carrying frame-shift BRCA1/2 mutations came from restored BRCA1/2 expression and HR function due to secondary intragenic mutations that corrected the open reading frames of mutated BRCA1/2. C1 [Wang, Weixin; Figg, William D.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Med Oncol Branch, Bldg 10,Room 5A01, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 FU Intramural NIH HHS [Z01 BC010627-04] NR 16 TC 22 Z9 25 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JUL PY 2008 VL 7 IS 7 BP 1004 EP 1005 DI 10.4161/cbt.7.7.6409 PG 2 WC Oncology SC Oncology GA 338RA UT WOS:000258524300004 PM 18720553 ER PT J AU Maher, SG Sheikh, F Scarzello, AJ Romero-Weaver, AL Baker, DP Donnelly, RP Gamero, AM AF Maher, Stephen G. Sheikh, Faruk Scarzello, Anthony J. Romero-Weaver, Ana L. Baker, Darren P. Donnelly, Raymond P. Gamero, Ana M. TI IFN alpha and IFN lambda differ in their antiproliferative effects and duration of JAK/STAT signaling activity SO CANCER BIOLOGY & THERAPY LA English DT Article DE interferon-alpha; interferon-lambda; STAT; antiproliferation; apoptosis ID POTENT ANTIVIRAL ACTIVITY; C VIRUS-REPLICATION; TRANSCRIPTIONAL ACTIVATION; CELL CARCINOMA; IN-VIVO; INTERFERON; EXPRESSION; INFECTION; INDUCE; STAT3 AB Interferon (IFN)lambda, also known as IL-28A, IL-28B or IL-29, is a new type III IFN, which like type I IFN(alpha/beta), activates common elements of the JAK/STAT signaling pathway and exhibits anti-proliferative activity. Currently, IFN alpha is used in the treatment of certain forms of cancer, but its antitumor effects are limited and associated with high toxicity. In this study, we determined whether IFN lambda induced the same level of cell growth inhibition relative to IFN alpha. To this effect HaCaT cells, which are typically growth inhibited by IFN alpha, underwent apoptosis in response to IFN lambda. Next, in contrast to IFN alpha stimulation, IFN lambda prolonged the duration of activated STAT1 and STAT2. Furthermore, the kinetics of IFN-stimulated genes was different as IFN lambda induced a delayed but stronger induction of IFN-responsive genes. Components of the JAK/STAT pathway remained essential for the antiproliferative effects of IFN alpha and IFN lambda. IFN lambda-induced persistence of STAT activation required de novo protein synthesis and was in part due to a delay in STAT2 inactivation. Thus our data demonstrate that the duration of IFN lambda signaling is different from that of IFN alpha, and that IFN lambda could be a suitable cytokine to evaluate for cancer therapy. C1 [Scarzello, Anthony J.; Gamero, Ana M.] NCI, Canc & Inflammat Program, Expt Immunol Lab, NIH, Frederick, MD USA. [Maher, Stephen G.] Univ Dublin Trinity Coll, Dept Surg, Dublin 2, Ireland. [Romero-Weaver, Ana L.] Thomas Jefferson Univ, Dept Canc Biol, Philadelphia, PA 19107 USA. [Baker, Darren P.] Biogen Idec Inc, Cambridge, MA USA. [Donnelly, Raymond P.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD USA. RP Gamero, AM (reprint author), Temple Univ, Sch Med, Dept Biochem, 3440 N Broad St, Philadelphia, PA 19140 USA. EM gameroa@mail.nih.gov OI Maher, Stephen/0000-0003-0126-7906 FU National Cancer Institute, National Institutes of Health [N01-CO-12400]; NIH FX We thank Dr. Howard Young for helpful discussions, Dr. Giorgio Trinchieri for critical reading of this manuscript and Dr. Veronica Hall for technical assistance with the quantitative RT-PCR system. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health under Contract No. N01-CO-12400. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 26 TC 101 Z9 115 U1 2 U2 10 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JUL PY 2008 VL 7 IS 7 BP 1109 EP 1115 DI 10.4161/cbt.7.7.6192 PG 7 WC Oncology SC Oncology GA 338RA UT WOS:000258524300024 PM 18698163 ER PT J AU Bernardi, RJ Bomgaars, L Fox, E Balis, FM Egorin, MJ Lagattuta, TF Aikin, A Whitcomb, P Renbarger, J Lieberman, FS Berg, SL Blaney, SM AF Bernardi, Ronald J. Bomgaars, Lisa Fox, Elizabeth Balis, Frank M. Egorin, Merrill J. Lagattuta, Theodore F. Aikin, Alberta Whitcomb, Patricia Renbarger, Jamie Lieberman, Frank S. Berg, Stacey L. Blaney, Susan M. TI Phase I clinical trial of intrathecal gemcitabine in patients with neoplastic meningitis SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE intrathecal; gemcitabine; phase I; pharmacokinetic ID CELL LUNG-CANCER; CEREBROSPINAL-FLUID; NONHUMAN-PRIMATES; CYTOSINE-ARABINOSIDE; CONTINUOUS INFUSION; PHARMACOKINETICS; CHEMOTHERAPY; CARCINOMA; 2',3'-DIDEOXYCYTIDINE; METABOLISM AB Purpose A phase I study of intrathecal (IT) gemcitabine was performed to define a safe dose and characterize the toxicity profile and CSF pharmacokinetics of gemcitabine and its major metabolite 2',2'-difluoro-deoxyuridine (dFdU) in patients 3 years of age and older with neoplastic meningitis. Experimental design Gemcitabine was administered via Ommaya reservoir or lumbar puncture at three dose levels: 5 mg weekly, 5 mg twice-weekly, and 10 mg twice-weekly using a standard phase I dose escalation design. Serial CSF samples were obtained for pharmacokinetic studies in seven patients with Ommaya reservoirs. Serial blood samples for pharmacokinetic studies were also obtained from three patients. Results Ten patients were enrolled in this study. Significant neurological toxicities occurred in two patients including myelitis in a patient at the 5 mg twice-weekly dose level and somnolence in a patient at the 10 mg twice-weekly dose level. No complete responses were seen; however, three patients had stable disease. Gemcitabine was rapidly eliminated from the CSF with a terminal half-life of 61 +/- 50 min. No gemcitabine or dFdU was detected in plasma. Conclusions IT gemcitabine was associated with significant neurotoxicity; therefore, its further development for IT use is not recommended. C1 [Blaney, Susan M.] Texas Childrens Canc Ctr, Houston, TX 77030 USA. [Bernardi, Ronald J.; Bomgaars, Lisa; Renbarger, Jamie; Berg, Stacey L.; Blaney, Susan M.] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. [Fox, Elizabeth; Balis, Frank M.; Aikin, Alberta; Whitcomb, Patricia] NCI, Pediat Oncol Branch, NIH Bethesda, Bethesda, MD 20892 USA. [Egorin, Merrill J.; Lagattuta, Theodore F.] Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, Pittsburgh, PA 15213 USA. [Egorin, Merrill J.; Lieberman, Frank S.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Egorin, Merrill J.; Lieberman, Frank S.] Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15213 USA. RP Blaney, SM (reprint author), Texas Childrens Canc Ctr, 6621 Fannin,MC 1410-00, Houston, TX 77030 USA. EM sblaney@txccc.org FU NCATS NIH HHS [UL1 TR000005] NR 29 TC 14 Z9 15 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JUL PY 2008 VL 62 IS 2 BP 355 EP 361 DI 10.1007/s00280-007-0601-x PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 300WH UT WOS:000255855500023 PM 17909804 ER PT J AU Beumer, JH Parise, RA Newman, EM Doroshow, JH Synold, TW Lenz, HJ Egorin, MJ AF Beumer, Jan H. Parise, Robert A. Newman, Edward M. Doroshow, James H. Synold, Timothy W. Lenz, Heinz-Josef Egorin, Merrill J. TI Concentrations of the DNA methyltransferase inhibitor 5-fluoro-2 '-deoxycytidine (FdCyd) and its cytotoxic metabolites in plasma of patients treated with FdCyd and tetrahydrouridine (THU) SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE metabolism; pyrimidine; DNA methylation inhibitor; phase I; tetrahydrouridine ID CYTOSINE-ARABINOSIDE; CYTIDINE DEAMINASE; PHARMACOKINETICS; CARCINOMA; MICE; 5-FLUORODEOXYCYTIDINE; 5-FLUOROURACIL; LEUKEMIA; THERAPY AB Purpose Although the DNA methyltransferase inhibitor 5-fluoro-2'-deoxycytidine (FdCyd), is being evaluated clinically, it must be combined with the cytidine deaminase inhibitor tetrahydrouridine (THU) to prevent rapid metabolism of FdCyd to the pharmacologically active, yet unwanted, metabolites 5-fluoro-2'-deoxyuridine (FdUrd), 5-fluorouracil (FU), and 5-fluorouridine (FUrd). We assessed plasma concentrations of FdCyd and metabolites in patients receiving FdCyd and THU. Methods We validated an LC-MS/MS assay, developed for a preclinical study, to quantitate FdCyd and metabolites in human plasma. Patients were treated with five daily, 3-h infusions of FdCyd at doses of 5-80 mg/m(2) with 350 mg/m(2) THU. Plasma was obtained during, and before the end of infusions on days 1 and 5. Results The lower limits of quantitation for FU, FdUrd, FUrd, FC and FdCyd were 1, 1.5, 10, 3, and 10 ng/ml, respectively. Plasma FdCyd increased with dose, from 19-96 ng/ml at 5 mg/m(2) to 1,600-1,728 ng/ml at 80 mg/m(2). FdUrd was undetectable in patients treated with FdCyd doses < 20 mg/m(2), and increased from 2.3 ng/ml at 20 mg/m(2) to 3.5-5.7 ng/ml at 80 mg/m(2). FU increased from 1.2-5.5 ng/ml at 5 mg/m(2) to 6.0-12 ng/ml at 80 mg/m(2). Conclusions By co-administering FdCyd with THU, FdCyd plasma concentrations were achieved that are known to inhibit DNA methylation in vitro. The accompanying plasma FU and FdUrd concentrations are < 10% those observed after therapeutic infusions of FU or FdUrd, while FdCyd levels are well above those required to inhibit methylation in vitro. Therefore, inhibition of DNA methylation with FdCyd and THU appears feasible. C1 [Beumer, Jan H.; Parise, Robert A.; Egorin, Merrill J.] Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, Pittsburgh, PA 15213 USA. [Beumer, Jan H.] Univ Pittsburgh, Dept Pharmaceut Sci, Sch Pharm, Pittsburgh, PA 15213 USA. [Newman, Edward M.] Beckman Res Inst City Hope, Div Mol Med, Duarte, CA 91010 USA. [Newman, Edward M.; Synold, Timothy W.] City Hope Natl Med Ctr, Div Med Oncol & Therapeut Res, Duarte, CA 91010 USA. [Doroshow, James H.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Lenz, Heinz-Josef] Univ So Calif, Norris Canc Ctr, Los Angeles, CA 90033 USA. [Egorin, Merrill J.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15261 USA. [Egorin, Merrill J.] Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15261 USA. RP Beumer, JH (reprint author), Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, Room G-27D,Hillman Res Pavilion,5117 Ctr Ave, Pittsburgh, PA 15213 USA. EM beumerjh@upmc.edu OI Beumer, Jan/0000-0002-8978-9401 FU NCI NIH HHS [N01-CM-52202, P30CA33572, U01 CA62505, U01 CA062505, P30CA47904] NR 19 TC 44 Z9 48 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JUL PY 2008 VL 62 IS 2 BP 363 EP 368 DI 10.1007/s00280-007-0603-8 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 300WH UT WOS:000255855500024 PM 17899082 ER PT J AU Singletary, K Milner, J AF Singletary, Keith Milner, John TI Diet, autophagy, and cancer: A review SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID PROGRAMMED CELL-DEATH; ENDOPLASMIC-RETICULUM STRESS; MALIGNANT GLIOMA-CELLS; ACTIVATED PROTEIN-KINASE; RESVERATROL-INDUCED APOPTOSIS; ORIDONIN-INDUCED AUTOPHAGY; BREAST-TUMOR CELLS; OXIDATIVE STRESS; UP-REGULATION; IN-VITRO AB A host of dietary factors can influence various cellular processes and thereby potentially influence overall cancer risk and tumor behavior. In many cases, these factors suppress cancer by stimulating programmed cell death. However, death not only can follow the well-characterized type I apoptotic pathway but also can proceed by nonapoptotic modes such as type II (macro-autophagy-related) and type III (necrosis) or combinations thereof. In contrast to apoptosis, the induction of macroautophagy may contribute to either the survival or death of cells in response to a stressor. This review highlights current knowledge and gaps in our understanding of the interactions among bioactive food constituents, autophagy, and cancer. Whereas a variety of food components including vitamin D, selenium, curcumin, resveratrol, and genistein have been shown to stimulate autophagy vacuolization, it is often difficult to determine if this is a protumorigenic or antitumorigenic response. Additional studies are needed to examine dose and duration of exposures and tissue specificity in response to bioactive food components in transgenic and knockout models to resolve the physiologic implications of early changes in the autophagy process. C1 [Singletary, Keith] Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA. [Milner, John] NCI, Nutr Sci Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. RP Singletary, K (reprint author), Univ Illinois, Dept Food Sci & Human Nutr, 905 S Goodwin Ave, Urbana, IL 61801 USA. EM kws@illinois.edu NR 214 TC 78 Z9 81 U1 3 U2 21 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 2008 VL 17 IS 7 BP 1596 EP 1610 DI 10.1158/1055-9965.EPI-07-2917 PG 15 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 327NJ UT WOS:000257735500005 PM 18628411 ER PT J AU Shapiro, JA Seeff, LC Thompson, TD Nadel, MR Klabunde, CN Vernon, SW AF Shapiro, Jean A. Seeff, Laura C. Thompson, Trevor D. Nadel, Marion R. Klabunde, Carrie N. Vernon, Sally W. TI Colorectal cancer test use from the 2005 National Health Interview Survey SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FECAL-OCCULT-BLOOD; PRIMARY-CARE PHYSICIANS; MEDICAL-RECORD AUDIT; UNITED-STATES; SCREENING SIGMOIDOSCOPY; SELF-REPORT; MORTALITY; PATTERNS; WOMEN; SURVEILLANCE AB Background: Screening is effective in reducing colorectal cancer mortality. Recommended colorectal cancer screening options include a home fecal occult blood test (FOBT) or colorectal endoscopy (sigmoidoscopy or colonoscopy). Past surveys have indicated that colorectal cancer screening prevalence in the United States is low. The purpose of this analysis was to determine the prevalence of colorectal cancer test use in the United States by various factors and to examine reasons for not having a colorectal cancer test. Methods: Data on respondents ages >= 50 years from the 2005 National Health Interview Survey (n = 13,269) were analyzed. The proportion of the U.S. population that had home FOBT within the past year or endoscopy within the past 10 years was examined by sociodemographic, health-care access, and other health-related factors. Reported reasons for not having FOBT or endoscopy were also analyzed. Results: The age-standardized proportion of respondents who reported FOBT within the past year and/or endoscopy within the past 10 years was 50.0% [95% confidence interval (95% CI), 48.8-51.2]. Colorectal cancer testing rates were particularly low among people without health-care coverage (24.1%; 95% CI, 19.2-29.7) or without a usual source of health care (24.7%; 95% Cl, 20.8-29.0). The most commonly reported reason for not having a colorectal cancer test was "never thought about it." Conclusions: In 2005, about half of Americans ages >= 50 years did not have appropriate colorectal cancer testing. Increased efforts to expand health-care coverage or to provide colorectal cancer tests to people without health-care coverage are needed to increase colorectal cancer screening. C1 [Shapiro, Jean A.; Seeff, Laura C.; Thompson, Trevor D.; Nadel, Marion R.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA 30341 USA. [Klabunde, Carrie N.] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Vernon, Sally W.] Univ Texas Houston, Sch Publ Hlth, Div Hlth Promot & Behav Sci, Houston, TX USA. RP Shapiro, JA (reprint author), Ctr Dis Control & Prevent, Div Canc Prevent & Control, 4770 Buford Highway NE,Mailstop K-55, Atlanta, GA 30341 USA. EM zga9@cdc.gov NR 42 TC 159 Z9 161 U1 2 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 2008 VL 17 IS 7 BP 1623 EP 1630 DI 10.1158/1055-9965.EPI-07-2838 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 327NJ UT WOS:000257735500007 PM 18628413 ER PT J AU Eng-Wong, J Orzano-Birgani, J Chow, CK Venzon, D Yao, JH Galbo, CE Zujewski, JA Prindiville, S AF Eng-Wong, Jennifer Orzano-Birgani, Jennifer Chow, Catherine K. Venzon, David Yao, Jianhua Galbo, Claudia E. Zujewski, Jo Anne Prindiville, Sheila TI Effect of raloxifene on mammographic density and breast magnetic resonance imaging in premenopausal women at increased risk for breast cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HORMONE REPLACEMENT THERAPY; POSTMENOPAUSAL WOMEN; BINDING PROTEIN-3; TAMOXIFEN; MRI; ASSOCIATION; FEATURES; TRIAL AB Background: Mammographic density is a risk factor for breast cancer. Mammographic density and breast magnetic resonance imaging (MRI) volume (MRIV) assess the amount of fibroglandular tissue in the breast. Mammographic density and MRIV can be modulated with hormonal interventions, suggesting that these imaging modalities may be useful as surrogate end-point biomarkers for breast cancer chemoprevention trials. We evaluated the effect of raloxifene on mammographic density and MRIV in premenopausal women at increased risk for breast cancer. Methods: Mammograms and MRI were obtained at baseline and after 1 and 2 years of 60 mg raloxifene by mouth daily for 27 premenopausal women. Mammographic percent dense area was calculated using a semiquantitative thresholding technique. T-1-weighted spoiled gradient-echo MRI with fat suppression was used to determine breast MRIV using a semiautomatic method. Mean change in mammographic density and median change in MRIV were assessed by the Wilcoxon signed-rank test. Results: No significant change in mammographic density was seen after treatment with raloxifene. Mean change after 1 year was 1% [95% confidence interval (95% CI), -3 to +5] and after 2 years was 1% (95% CI, -2 to +5). MRIV decreased on raloxifene. Median relative change in MRIV after 1 year was -17% (95% Cl, -28 to -9; P 0.0017) and after 2 years was -16% (95% CI, -31 to -4; P 0.0004). Conclusions: In high-risk premenopausal women, mammographic density did not change on raloxifene, whereas MRIV significantly declined. Our findings suggest that MRIV is a promising surrogate biomarker in premenopausal women at increased risk for breast cancer and should be investigated further in breast cancer prevention trials. C1 [Eng-Wong, Jennifer; Orzano-Birgani, Jennifer; Zujewski, Jo Anne; Prindiville, Sheila] NCI, Ctr Canc Res, Med Oncol Branch, Bethesda, MD 20892 USA. [Venzon, David] NCI, Ctr Canc Res, Biostat & Data Management Sect, Bethesda, MD 20892 USA. [Chow, Catherine K.; Yao, Jianhua] NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. [Galbo, Claudia E.] Uniformed Serv Univ Hlth Sci, Dept Radiol Sci, Bethesda, MD 20814 USA. RP Eng-Wong, J (reprint author), Georgetown Univ, Vincent T Lombardi Canc Res Ctr, 2nd Floor,3800 Reservoir Rd NW, Washington, DC 20007 USA. EM je95@georgetown.edu FU Intramural NIH HHS [NIH0010039646]; PHS HHS [NIH0010039646] NR 34 TC 42 Z9 43 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 2008 VL 17 IS 7 BP 1696 EP 1701 DI 10.1158/1055-9965.EPI-07-2752 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 327NJ UT WOS:000257735500017 PM 18583470 ER PT J AU Lord, SJ Bernstein, L Johnson, KA Malone, KE McDonald, JA Marchbanks, PA Simon, MS Strom, BL Press, MF Folger, SG Burkman, RT Deapen, D Spirtas, R Ursin, G AF Lord, Sarah J. Bernstein, Leslie Johnson, Karen A. Malone, Kathleen E. McDonald, Jill A. Marchbanks, Polly A. Simon, Michael S. Strom, Brian L. Press, Michael F. Folger, Suzanne G. Burkman, Ronald T. Deapen, Dennis Spirtas, Robert Ursin, Giske TI Breast cancer risk and hormone receptor status in older women by parity, age of first birth, and breastfeeding: A case-control study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID REPRODUCTIVE FACTORS; TRANSIENT INCREASE; PREGNANCY; COUNTRIES; ESTROGEN AB Background: Early age at first birth and multiparity reduce the risk of estrogen receptor-progesterone receptor (ERPR)-positive breast cancer, whereas breastfeeding reduces the risk of both ERPR-positive and ERPR-negative cancers. Methods: We used multivariable logistic regression analysis to investigate whether age at first birth (<25 or >= 25 years) and breastfeeding (ever/never) modify the long-term effect of parity on risk of ERPR-positive and ERPR-negative cancer using 1,457 incident breast cancer cases and 1,455 controls ages >= 55 years who participated in the Women's Contraceptive and Reproductive Experiences Study. Results: Women who gave birth before age 25 years had a 36% reduced risk of breast cancer compared with nulligravida that was not observed for women who started their families at an older age (P(heterogeneity)= 0.0007). This protective effect was restricted to ERPR-positive breast cancer (P(heterogeneity)= 0.004). Late age at first birth increased the risk of ERPR-negative cancers. Additional births reduced the risk of ERPR-positive cancers among women with an early first birth (P(trend) = 0.0001) and among women who breastfed (P(trend) = 0.004) but not among older mothers or those who never breastfed. In women with a late first birth who never breastfed, multiparity was associated with increased risk of breast cancer. Conclusions: These findings suggest that the effect of parity on a woman's long-term risk of breast cancer is modified by age at first full-term pregnancy and possibly by breastfeeding. C1 [Bernstein, Leslie; Press, Michael F.; Deapen, Dennis; Ursin, Giske] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90089 USA. [Lord, Sarah J.] Univ Sydney, Natl Hlth & Med Res Council, Clin Trials Ctr, Sydney, NSW 2006, Australia. [Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA. [Johnson, Karen A.] NCI, Breast & Gynecol Canc Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. [Spirtas, Robert] Natl Inst Child Hlth & Dev, Contracept & Reprod Hlth Branch, Populat Res Ctr, Bethesda, MD USA. [Malone, Kathleen E.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Malone, Kathleen E.] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. [McDonald, Jill A.; Marchbanks, Polly A.; Folger, Suzanne G.] Ctr Dis Control & Prevent, Div Reprod Hlth, Atlanta, GA USA. [Simon, Michael S.] Wayne State Univ, Karmanos Canc Inst, Div Hematol & Oncol, Detroit, MI USA. [Strom, Brian L.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Strom, Brian L.] Univ Penn, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Burkman, Ronald T.] Tufts Univ, Sch Med, Baystate Med Ctr, Dept Obstet & Gynecol, Springfield, MA 01199 USA. [Ursin, Giske] Univ Oslo, Inst Basic Med Sci, Dept Nutr, Oslo, Norway. RP Ursin, G (reprint author), Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Room 4407,1441 Eastlake Ave, Los Angeles, CA 90089 USA. EM gursin@usc.edu OI Lord, Sarah J/0000-0003-2763-5949 FU NCI NIH HHS [N01 CN 0532, N01 CN 65064, N01 CN065064, N01 PC 67006, N01 PC 67010, N01 PC067006, N01 PC067006-009, N01 PC067010, R01 CA077398, R01 CA098858, R01 CA098858-01A2, R01 CA098858-02, R01 CA098858-03, R01 CA098858-04, R01 CA098858-05]; NICHD NIH HHS [N01 HD 23166, N01 HD 33168, N01 HD 33174, N01 HD 33175, N01 HD 33276, N01 HD023166, N01 HD033168, N01 HD033174, N01 HD033175, Y01 HD007022] NR 22 TC 46 Z9 49 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 2008 VL 17 IS 7 BP 1723 EP 1730 DI 10.1158/1055-9965.EPI-07-2824 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 327NJ UT WOS:000257735500022 PM 18628424 ER PT J AU Guo, XC O'Brien, SJ Zeng, Y Nelson, GW Winkler, CA AF Guo, Xiuchan O'Brien, Stephen J. Zeng, Yi Nelson, George W. Winkler, Cheryl A. TI GSTM1 and GSTT1 gene deletions and the risk for nasopharyngeal carcinoma in Han Chinese SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID S-TRANSFERASE M1; BREAST-CANCER RISK; NECK-CANCER; GLUTATHIONE; GENOTYPES; POLYMORPHISMS; T1; SUSCEPTIBILITY; ASSOCIATION; GSTP1 AB Southern China is a major nasopharyngeal carcinoma-endemic region. Environmental factors and genetic susceptibility contribute to nasopharyngeal carcinoma development in this area. Polymorphic deletions of GSTM1 and GSTT1 genes involved in the detoxification of potentially carcinogenic agents may be a risk factor for nasopharyngeal carcinoma. To investigate the roles of genetic variations of GSTM1 and GSTT1 in nasopharyngeal carcinoma susceptibility in the Chinese population, we conducted a case-control study of 350 nasopharyngeal carcinoma cases and 622 controls. GSTM1 and GSTT1 deletion variants were genotyped by multiplex PCR assays. Logistic regression analysis was used to estimate odds ratios and 95% confidence intervals (95% Cl). No significant association was observed for either GSTM1- or GSTT1-null genotype independently in the contribution to nasopharyngeal carcinoma risk. To explore possible joint effects of the GSTM1- and GSTT1-null polymorphisms with each other and with other risk factors for nasopharyngeal carcinoma, we examined the association between each combined genotype and the risk for nasopharyngeal carcinoma stratified by gender and EBV replication status. We found that individuals who carried GSTM1/GSTT1-double null genotype had a higher risk for nasopharyngeal carcinoma in the male population (odds ratio, 1.76; 95% confidence interval, 1.04-2.97; P = 0.03); however, this was not significant after correction for multiple comparisons. No statistical difference was found between cases and controls in females and the subpopulation positive for immunoglobulin A antibodies to EBV capsid antigen for combined genotypes. Our results suggest that the GSTM1/GSTT1-double null genotype may be a risk factor for nasopharyngeal carcinoma among males in southern China, but this result warrants confirmation in other studies. C1 [Guo, Xiuchan; Nelson, George W.; Winkler, Cheryl A.] NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Guo, Xiuchan; Zeng, Yi] Chinese CDC, Inst Viral Dis Control & Prevent, State Key Lab Infect Dis Prevent & Control, Beijing, Peoples R China. [O'Brien, Stephen J.] NCI, Lab Genom Divers, Ctr Canc Res, NIH, Frederick, MD 21702 USA. RP Winkler, CA (reprint author), NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. EM winkler@ncifcrf.gov FU NCI NIH HHS [N01 CO 12400] NR 25 TC 26 Z9 26 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 2008 VL 17 IS 7 BP 1760 EP 1763 DI 10.1158/1055-9965.EPI-08-0149 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 327NJ UT WOS:000257735500027 PM 18628429 ER PT J AU Max, JB Limburg, PJ Ogunseitan, A Stolzenberg-Solomon, RZ Vierkant, RA Pollak, MJ Sellers, TA Virtamo, J Cerhan, JR Albanes, D AF Max, Joshua B. Limburg, Paul J. Ogunseitan, Adeboye Stolzenberg-Solomon, Rachael Z. Vierkant, Robert A. Pollak, Michael J. Sellers, Thomas A. Virtamo, Jarmo Cerhan, James R. Albanes, Demetrius TI IGF-I, IGFBP-3, and IGF-I/IGFBP-3 ratio: No association with incident colorectal cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CASE-COHORT DESIGN; GROWTH-FACTOR-I; C-PEPTIDE; FOLLOW-UP; INSULIN; RISK; REGRESSION C1 [Limburg, Paul J.] Mayo Clin, Div Gastroenterol & Hepatol, Coll Med, Rochester, MN 55905 USA. [Stolzenberg-Solomon, Rachael Z.; Albanes, Demetrius] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Pollak, Michael J.] McGill Univ, Jewish Gen Hosp, Canc Prevent Program, Montreal, PQ H3T 1E2, Canada. [Sellers, Thomas A.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Virtamo, Jarmo] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland. RP Limburg, PJ (reprint author), Mayo Clin, Div Gastroenterol & Hepatol, Coll Med, 200 1st St SW, Rochester, MN 55905 USA. EM limburg.paul@mayo.edu RI Pollak, Michael/G-9094-2011; Albanes, Demetrius/B-9749-2015; OI Pollak, Michael/0000-0003-3047-0604; Cerhan, James/0000-0002-7482-178X; Vierkant, Robert/0000-0001-6242-5221 FU NCI NIH HHS [N01 CN045165, K07 CA 92216, K07 CA092216, N01 CN 45035, N01 CN 45165, N01 CN045035] NR 12 TC 7 Z9 7 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 2008 VL 17 IS 7 BP 1832 EP 1834 DI 10.1158/1055-9965.EPI-08-0345 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 327NJ UT WOS:000257735500036 PM 18628438 ER PT J AU Kerstann, KF Bradford, PT Steighner, R Calista, D Fargnoli, MC Peris, K Scaini, MC Menin, C Ghiorzo, P Bianchi-Scarra, G Goldstein, AM Landi, MT AF Kerstann, Kimberly F. Bradford, Porcia T. Steighner, Robert Calista, Donato Fargnoli, Maria Concetta Peris, Ketty Scaini, Maria Chiara Menin, Chiara Ghiorzo, Paola Bianchi-Scarra, Giovanna Goldstein, Alisa M. Landi, Maria Teresa TI No evidence for linkage with melanoma in Italian melanoma-prone families SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID MALIGNANT-MELANOMA; GENETIC-HETEROGENEITY; DYSPLASTIC NEVUS; CANCER REGISTRY; SUSCEPTIBILITY; P16(INK4A); MUTATIONS; TUMORS; LOCUS; CDK4 C1 [Landi, Maria Teresa] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. [Calista, Donato] Maurizio Bufalini Hosp, Dept Dermatol, Cesena, Italy. [Fargnoli, Maria Concetta; Peris, Ketty] Univ Aquila, Dept Dermatol, I-67100 Laquila, Italy. [Scaini, Maria Chiara] Univ Padua, Dept Oncol & Surg Sci, Padua, Italy. [Menin, Chiara] IRCCS, Ist Oncol Veneto, Padua, Italy. [Ghiorzo, Paola; Bianchi-Scarra, Giovanna] Univ Genoa, Dept Oncol Biol & Genet, Genoa, Italy. RP Landi, MT (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, 6120 Execut Blvd,EPS 7114, Bethesda, MD 20892 USA. EM landim@mail.nih.gov RI Bianchi Scarra, Giovanna/G-8933-2014; SCAINI, MARIA CHIARA/J-5270-2016; Menin, Chiara/L-5770-2016; OI Bianchi Scarra, Giovanna/0000-0002-6127-1192; SCAINI, MARIA CHIARA/0000-0002-9583-3034; Menin, Chiara/0000-0002-8907-772X; Peris, Ketty/0000-0002-5237-0463; Fargnoli, Maria Concetta/0000-0002-7249-2556 FU Intramural NIH HHS NR 20 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 2008 VL 17 IS 7 BP 1838 EP 1840 DI 10.1158/1055-9965.EPI-08-0264 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 327NJ UT WOS:000257735500038 PM 18628440 ER PT J AU Sithanandam, G Anderson, LM AF Sithanandam, G. Anderson, L. M. TI The ERBB3 receptor in cancer and cancer gene therapy SO CANCER GENE THERAPY LA English DT Review DE ERBB3; cancer biology; cancer therapy ID EPIDERMAL-GROWTH-FACTOR; CELL LUNG-CANCER; HUMAN BREAST-CANCER; TYROSINE KINASE INHIBITOR; MAMMARY EPITHELIAL-CELLS; PHASE-II TRIAL; C-ERBB-3 PROTEIN EXPRESSION; NEU DIFFERENTIATION FACTOR; MESSENGER-RNA EXPRESSION; PROSTATIC INTRAEPITHELIAL NEOPLASIA AB ERBB3, a member of the epidermal growth factor receptor ( EGFR) family, is unique in that its tyrosine kinase domain is functionally defective. It is activated by neuregulins, by other ERBB and nonERBB receptors as well as by other kinases, and by novel mechanisms. Downstream it interacts prominently with the phosphoinositol 3-kinase/AKT survival/mitogenic pathway, but also with GRB, SHC, SRC, ABL, rasGAP, SYK and the transcription regulator EBP1. There are likely important but poorly understood roles for nuclear localization and for secreted isoforms. Studies of ERBB3 expression in primary cancers and of its mechanistic contributions in cultured cells have implicated it, with varying degrees of certainty, with causation or sustenance of cancers of the breast, ovary, prostate, certain brain cells, retina, melanocytes, colon, pancreas, stomach, oral cavity and lung. Recent results link high ERBB3 activity with escape from therapy targeting other ERBBs in lung and breast cancers. Thus a wide and centrally important role for ERBB3 in cancer is becoming increasingly apparent. Several approaches for targeting ERBB3 in cancers have been tested or proposed. Small inhibitory RNA (siRNA) to ERBB3 or AKT is showing promise as a therapeutic approach to treatment of lung adenocarcinoma. C1 [Sithanandam, G.] NCI, Comparat Carcinogenesis Lab, SAIC Frederick, Frederick, MD 21702 USA. RP Sithanandam, G (reprint author), NCI, Comparat Carcinogenesis Lab, SAIC Frederick, Bldg 538, Frederick, MD 21702 USA. EM sithanan@ncifcrf.gov FU Intramural NIH HHS [Z01 BC005399-24]; NCI NIH HHS [N01 CO012400, N01-CO-12400, N01CO12400] NR 439 TC 108 Z9 111 U1 0 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 EI 1476-5500 J9 CANCER GENE THER JI Cancer Gene Ther. PD JUL PY 2008 VL 15 IS 7 BP 413 EP 448 DI 10.1038/cgt.2008.15 PG 36 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 312HJ UT WOS:000256659500001 PM 18404164 ER PT J AU Castro, DJ Baird, WM Pereira, CB Giovanini, J Lohr, CV Fischer, KA Yu, Z Gonzalez, FJ Krueger, SK Williams, DE AF Castro, David J. Baird, William M. Pereira, Clifford B. Giovanini, Jack Loehr, Christiane V. Fischer, Kay A. Yu, Zhen Gonzalez, Frank J. Krueger, Sharon K. Williams, David E. TI Fetal Mouse Cyp1b1 and Transplacental Carcinogenesis from Maternal Exposure to Dibenzo(a,l)pyrene SO CANCER PREVENTION RESEARCH LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; CYTOCHROME P4501B1 VARIANTS; NON-HODGKINS-LYMPHOMA; IN-UTERO EXPOSURE; METABOLIC-ACTIVATION; CHILDHOOD LEUKEMIA; PERINATAL CARCINOGENESIS; ADULT TISSUES; RISK; MICE AB Dibenzo(a,l)pyrene (DBP) is among the most potent carcinogenic polycyclic aromatic hydrocarbons. Previously, we showed that DBP administration to pregnant mice resulted in high mortality of offspring from an aggressive T-cell lymphoma. All mice that survive to 10 months of age exhibit lung tumors with high multiplicity. Recombinant cytochrome P450 (cyp) 1b1 from mice and the homologue 1B1 in humans exhibit high activity toward the metabolic activation of DBP. Targeted disruption of the cyp1b1 gene protects against most DBP-dependent cancers. Mice heterozygous for the disrupted cyp1b1 allele were used to examine the effect of cyp1b1 gene dosage on DBP transplacental carcinogenesis. Dams were treated with 1 or 15 mg/kg of DBP or 50 mg/kg of benzo(a) pyrene. Cyp1b1-null offspring did not develop lymphoma, whereas wild-type and heterozygous siblings, born to dams given the high dose of DBP, exhibited significant mortalities between 10 and 30 weeks of age. At 10 months, all groups had lung adenomas or carcinomas [9.5%, 40.3%, 25.6%, and 100% incidences for controls, benzo(a) pyrene, 1 and 15 mg/kg DBP, respectively]. Cyp1b1 status did not alter benzo(a) pyrene-dependent carcinogenesis. At 1 mg/kg DBP, cyp1b1 status altered the incidence of lung tumors (19.0, 27.8, and 28.6% for nulls, heterozygous, and wild-type, respectively). At 15 mg/kg, tumor multiplicities in cyp1b1 wild-type (9.3) and heterozygous (9.5) offspring were nearly twice that of cyp1b1-null siblings (5.0). These data confirm that cyp1b1 bioactivation of DBP occurs in fetal target tissues, following transplacental exposure, with the thymus and lung as primary and secondary targets, respectively. C1 [Castro, David J.; Baird, William M.; Williams, David E.] Oregon State Univ, Dept Environm & Mol Toxicol, Corvallis, OR 97331 USA. [Castro, David J.; Yu, Zhen; Krueger, Sharon K.; Williams, David E.] Oregon State Univ, Linus Pauling Inst, Corvallis, OR 97331 USA. [Baird, William M.; Pereira, Clifford B.; Loehr, Christiane V.; Fischer, Kay A.; Williams, David E.] Oregon State Univ, Environm Hlth Sci Ctr, Corvallis, OR 97331 USA. [Pereira, Clifford B.; Giovanini, Jack] Oregon State Univ, Dept Stat, Corvallis, OR 97331 USA. [Loehr, Christiane V.; Fischer, Kay A.] Oregon State Univ, Coll Vet Med, Corvallis, OR 97331 USA. [Gonzalez, Frank J.] NCI, Bethesda, MD 20892 USA. RP Williams, DE (reprint author), Oregon State Univ, Dept Environm & Mol Toxicol, ALS 1007, Corvallis, OR 97331 USA. EM david.williams@oregonstate.edu FU USPHS [CA90890, ES07060, ES00210]; NIH; The Linus Pauling Institute at Oregon State University FX Grant support: USPHS grants CA90890, ES07060, and ES00210 from the NIH and The Linus Pauling Institute at Oregon State University. NR 50 TC 26 Z9 26 U1 1 U2 15 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD JUL PY 2008 VL 1 IS 2 BP 128 EP 134 DI 10.1158/1940-6207.CAPR-07-0004 PG 7 WC Oncology SC Oncology GA 420MD UT WOS:000264293000009 PM 19138945 ER PT J AU Hucl, T Rago, C Gallmeier, E Brody, JR Gorospe, M Kern, SE AF Hucl, Tomas Rago, Carlo Gallmeier, Eike Brody, Jonathan R. Gorospe, Myriam Kern, Scott E. TI A syngeneic variance library for functional annotation of human variation: Application to BRCA2 SO CANCER RESEARCH LA English DT Article ID DNA-REPAIR DEFECT; HUMAN CANCER; IONIZING-RADIATION; TOPOISOMERASE-II; HUMAN BREAST; CELLS; MUTATIONS; MUTANT; RAD51; MODEL AB The enormous scope of natural human genetic variation is now becoming defined. To accurately annotate these variants, and to identify those with clinical importance, is often difficult to assess through functional assays. We explored systematic annotation by using homologous recombination to modify a native gene in hemizygous (wt/Delta exon) human cancer cells, generating a novel syngeneic variance library (SyVaL). We created a SyVaL of BRCA2 variants: nondeleterious, proposed deleterious, deleterious, and of uncertain significance. We found that the null states BRCA2(Delta ex11/Delta ex11) and BRCA2(Delta ex11/Y3308X) were deleterious as assessed by a loss of RAD51 focus formation on genotoxic damage and by acquisition of toxic hypersensitivity to mitomycin C and etoposide, whereas BRCA2(Delta ex11/Y3308Y), BRCA2(Delta ex11/P3292L) ,and BRCA2(Delta ex11/P3280H) had wild-type function. A proposed phosphorylation site at codon 3291 affecting function was confirmed by substitution of an acidic residue (glutamate, BRCA2(Delta ex11/S3291E)) for the native serine, but in contrast to a prior report, phosphorylation was dispensable (alanine, BRCA2(Delta ex11/S3291A)) for BRCA2-governed cellular phenotypes. These results show that SyVaLs offer a means to comprehensively annotate gene function, facilitating numerical and unambiguous readouts. SyVaLs may be especially useful for genes in which functional assays using exogenous expression are toxic or otherwise unreliable. They also offer a stable, distributable cellular resource for further research. C1 [Hucl, Tomas; Gallmeier, Eike; Brody, Jonathan R.; Kern, Scott E.] Johns Hopkins Univ, Dept Oncol, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. [Rago, Carlo] Johns Hopkins Univ, Howard Hughes Med Inst, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. [Rago, Carlo] Johns Hopkins Univ, Ludwig Ctr Canc Genet & Therapeut, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. [Gorospe, Myriam] NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Kern, SE (reprint author), Johns Hopkins Univ, Dept Oncol, Sidney Kimmel Comprehens Canc Ctr, 1650 Orleans St, Baltimore, MD 21231 USA. EM sk@jhmi.edu FU Intramural NIH HHS [Z01 AG000511-10]; NCI NIH HHS [P50 CA062924, CA88843, P50 CA088843, CA62924] NR 38 TC 30 Z9 30 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2008 VL 68 IS 13 BP 5023 EP 5030 DI 10.1158/0008-5472.CAN-07-6189 PG 8 WC Oncology SC Oncology GA 323AB UT WOS:000257415300012 PM 18593900 ER PT J AU King, KE Ponnamperuma, RM Allen, C Lu, H Duggal, P Chen, Z Van Waes, C Weinberg, WC AF King, Kathryn E. Ponnamperuma, Roshini M. Allen, Clint Lu, Hai Duggal, Praveen Chen, Zhong Van Waes, Carter Weinberg, Wendy C. TI The p53 homologue Delta Np63 alpha interacts with the nuclear factor-kappa B pathway to modulate epithelial cell growth SO CANCER RESEARCH LA English DT Article ID TRANSCRIPTION FACTOR REL; CHICKEN SPLEEN-CELLS; C-REL; EPIDERMAL DEVELOPMENT; P63 ISOFORMS; ACTIVATION; EXPRESSION; CARCINOMA; DISTINCT; ALPHA AB The p53 homologue Delta Np63 alpha is overexpressed and inhibits apoptosis in a subset of human squamous cell carcinomas (SCC). Here, we report that in normal keratinocytes over-expressing Delta Np63 alpha and in human squamous carcinoma cells, Delta Np63 alpha physically associates with phosphorylated, transcriptionally active nuclear c-Rel, a nuclear factor-kappa B family member, resulting in increased c-Rel nuclear accumulation. This accumulation and the associated enhanced proliferation driven by elevated Delta Np63 alpha are attenuated by c-Rel small interfering RNA or overexpression of mutant I kappa B alpha M, indicating that c-Rel-containing complex formation is critical to the ability of elevated Delta Np63 alpha to maintain proliferation in the presence of growth arresting signals. Consistent with a role in growth regulation, Delta Np63 alpha-c-Rel complexes bind a promoter motif and repress the cyclin-dependent kinase inhibitor p21WAF1 in both human squamous carcinoma cells and normal keratinocytes overexpressing Delta Np63 alpha. The relationship between Delta Np63 alpha and activated c-Rel is reflected in their strong nuclear staining in the proliferating compartment of primary head and neck SCC. This is the first report indicating that high levels of Delta Np63 alpha interact with activated c-Rel in keratinocytes and SCC, thereby promoting uncontrolled proliferation, a key alteration in the pathogenesis of cancers. C1 [Weinberg, Wendy C.] US FDA, Immunobiol Lab, Div Monoclonal Antibodies, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Allen, Clint; Lu, Hai; Duggal, Praveen; Chen, Zhong; Van Waes, Carter] Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, NIH, Bethesda, MD USA. RP Weinberg, WC (reprint author), US FDA, Immunobiol Lab, Div Monoclonal Antibodies, Off Biotechnol Prod,Ctr Drug Evaluat & Res, 29B Lincoln Dr,NIH Bldg 29B,Room 3NN04,HFD-123, Bethesda, MD 20892 USA. EM wendy.weinberg@fda.hhs.gov RI Weinberg, Wendy/A-8920-2009 FU Intramural NIH HHS [Z01 DC000016-14]; NIDCD NIH HHS [Z01 DC000016] NR 50 TC 25 Z9 25 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2008 VL 68 IS 13 BP 5122 EP 5131 DI 10.1158/0008-5472.CAN-07-6123 PG 10 WC Oncology SC Oncology GA 323AB UT WOS:000257415300023 PM 18593911 ER PT J AU Liang, XJ Choi, Y Sackett, DL Park, JK AF Liang, Xing-Jie Choi, Yong Sackett, Dan L. Park, John K. TI Nitrosoureas inhibit the stathmin-mediated migration and invasion of malignant glioma cells SO CANCER RESEARCH LA English DT Article ID GLIOBLASTOMA; RADIOTHERAPY; TEMOZOLOMIDE; SURGERY; TRIAL AB Malignant gliomas are the most common primary intrinsic brain tumors and are highly lethal. The widespread migration and invasion of neoplastic cells from the initial site of tumor formation into the surrounding brain render these lesions refractory to definitive surgical treatment. Stathmin, a microtubule-destabilizing protein that mediates cell cycle progression, can also regulate directed cell movement. Nitrosoureas, traditionally viewed as DNA alkylating agents, can also covalently modify proteins such as stathmin. We therefore sought to establish a role for stathmin in malignant glioma cell motility, migration, and invasion and determine the effects of nitrosoureas on these cell movement-related processes. Scratch wound-healing recovery, Boyden chamber migration, Matrigel invasion, and organotypic slice invasion assays were performed before and after the down-regulation of cellular stathmin levels and in the absence and presence of sublethal nitrosourea ([1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea]; CCNU) concentrations. We show that decreases in stathmin expression lead to significant decreases in malignant glioma cell motility, migration, and invasion. CCNU, at a concentration of 10 mu mol/L, causes similar significant decreases, even in the absence of any effects on cell viability. The direct inhibition of stathmin by CCNU is likely a contributing factor. These findings suggest that the inhibition of stathmin expression and function may be useful in limiting the spread of malignant gliomas within the brain, and that nitrosoureas may have therapeutic benefits in addition to their antiproliferative effects. C1 [Liang, Xing-Jie; Choi, Yong; Park, John K.] Natl Inst Neurol Disorders & Stroke, Surg & Mol Neurooncol Unit, Bethesda, MD USA. [Sackett, Dan L.] NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. [Liang, Xing-Jie] Natl Ctr Nanosci & Technol China, Beijing, Peoples R China. RP Park, JK (reprint author), 35 Convent Dr, Bethesda, MD 20892 USA. EM parkjk@ninds.nih.gov FU Intramural NIH HHS [Z01 NS003100-04, Z99 NS999999] NR 14 TC 25 Z9 25 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2008 VL 68 IS 13 BP 5267 EP 5272 DI 10.1158/0008-5472.CAN-07-6482 PG 6 WC Oncology SC Oncology GA 323AB UT WOS:000257415300039 PM 18593927 ER PT J AU Bonome, T Levine, DA Shih, J Randonovich, M Pise-Masison, CA Bogomolniy, F Ozbun, L Brady, J Barrett, JC Boyd, J Birrer, MJ AF Bonome, Tomas Levine, Douglas A. Shih, Joanna Randonovich, Mike Pise-Masison, Cindy A. Bogomolniy, Faina Ozbun, Laurent Brady, John Barrett, J. Carl Boyd, Jeff Birrer, Michael J. TI A gene signature predicting for survival in suboptimally debulked patients with ovarian cancer SO CANCER RESEARCH LA English DT Article ID EXPRESSION PATTERNS; STATISTICS; MICROARRAY; GROWTH; DNA; METHYLATION; RESISTANCE; CISPLATIN; TUMORS; SIRT1 AB Despite the existence of morphologically indistinguishable disease, patients with advanced ovarian tumors display a broad range of survival end points. We hypothesize that gene expression profiling can identify a prognostic signature accounting for these distinct clinical outcomes. To resolve survival-associated loci, gene expression profiling was completed for an extensive set of 185 (90 optimal/95 suboptimal) primary ovarian tumors using the Affymetrix human U133A microarray. Cox regression analysis identified probe sets associated with survival in optimally and suboptimally debulked tumor sets at a P value of <0.01. Leave-one-out cross-validation was applied to each tumor cohort and confirmed by a permutation test. External validation was conducted by applying the gene signature to a publicly available array database of expression profiles of advanced stage suboptimally debulked tumors. The prognostic signature successfully classified the tumors according to survival for suboptimally (P = 0.0179) but not optimally debulked (P = 0.144) patients. The suboptimal gene signature was validated using the independent set of tumors (odds ratio, 8.75; P = 0.0146). To elucidate signaling events amenable to therapeutic intervention in suboptimally debulked patients, pathway analysis was completed for the top 57 survival-associated probe sets. For suboptimally debulked patients, confirmation of the predictive gene signature supports the existence of a clinically relevant predictor, as well as the possibility of novel therapeutic opportunities. Ultimately, the prognostic classifier defined for suboptimally debulked tumors may aid in the classification and enhancement of patient outcome for this high-risk population. C1 [Bonome, Tomas; Ozbun, Laurent; Barrett, J. Carl; Birrer, Michael J.] NCI, Cell & Canc Biol Branch, NIH, Rockville, MD USA. [Shih, Joanna] NCI, Biometr Res Branch, NIH, Rockville, MD USA. [Randonovich, Mike; Pise-Masison, Cindy A.; Brady, John] NCI, Cellular Oncol Lab, NIH, Rockville, MD USA. [Levine, Douglas A.; Bogomolniy, Faina; Boyd, Jeff] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Birrer, MJ (reprint author), NCI, Bldg 37,Room 1130,9000 Rockville Pike, Bethesda, MD 20892 USA. EM birrerm@mail.nih.gov OI Levine, Douglas/0000-0003-1038-8232 FU NCI NIH HHS [U01 CA088175] NR 34 TC 145 Z9 147 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2008 VL 68 IS 13 BP 5478 EP 5486 DI 10.1158/0008-5472.CAN-07-6595 PG 9 WC Oncology SC Oncology GA 323AB UT WOS:000257415300063 PM 18593951 ER PT J AU Yuan, JM Chan, KK Coetzee, GA Castelao, JE Watson, MA Bell, DA Wang, RW Yu, MC AF Yuan, Jian-Min Chan, Kenneth K. Coetzee, Gerhard A. Castelao, J. Esteban Watson, Mary A. Bell, Douglas A. Wang, Renwei Yu, Mimi C. TI Genetic determinants in the metabolism of bladder carcinogens in relation to risk of bladder cancer SO CARCINOGENESIS LA English DT Article ID S-TRANSFERASE M1; CAFFEINE URINARY METABOLITES; CYTOCHROME-P450 1A2 ACTIVITY; HEMOGLOBIN ADDUCT LEVELS; PERMANENT HAIR-DYES; N-ACETYLTRANSFERASE; CYP1A2 GENE; COLORECTAL-CANCER; P4501A2 ACTIVITY; AROMATIC-AMINES AB Genetically determined factors that alter the metabolism of tobacco carcinogens can influence an individual's susceptibility to bladder cancer. The associations between the genotypes of glutathione S-transferase (GST) M1, GSTP1, GSTT1 and N-acetyltransferase (NAT) 1 and the phenotypes of NAT2 and cytochrome P450 (CYP) 1A2 and bladder cancer risk were examined in a case-control study involving 731 bladder cancer patients and 740 control subjects in Los Angeles County, California. Individual null/low-activity genotypes of GSTM1, GSTT1 and GSTP1 were associated with a 19-48% increase in odds ratio (OR) of bladder cancer. The strongest association was noted for GSTM1 [OR for the null genotype = 1.48, 95% confidence interval (CI) = 1.19-1.83]. When the three GST genes were examined together, there was a monotonic, statistically significant association between increasing number of null/low-activity genotypes and risk (P for trend = 0.002). OR (95% CI) for one and two or more null/low-activity GST genotypes was 1.42 (1.12-1.81) and 1.71 (1.2=-2.34), respectively, relative to the absence of null/low-activity GST genotype. NAT2 slow acetylation was associated with doubled risk of bladder cancer among individuals with known high exposures to carcinogenic arylamines (OR = 2.03, 95% CI = 1.12-3.69, P = 0.02). The effect of NAT2 slow acetylation was even stronger in the presence of two or more null/low-activity GST genotypes. There were no associations between bladder cancer risk and NAT1 genotype or CYP1A2 phenotype. C1 [Yuan, Jian-Min] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Mason Canc Ctr, Minneapolis, MN 55454 USA. [Chan, Kenneth K.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Coetzee, Gerhard A.; Castelao, J. Esteban] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Los Angeles, CA 90033 USA. [Watson, Mary A.; Bell, Douglas A.] NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Yuan, JM (reprint author), Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Mason Canc Ctr, 1300 S 2nd St,Suite 300, Minneapolis, MN 55454 USA. EM jyuan@umn.edu OI Yuan, Jian-Min/0000-0002-4620-3108 FU Intramural NIH HHS [Z01 ES046008-17]; NCI NIH HHS [R01 CA65726, P01 CA17054, R01 CA114665]; NIEHS NIH HHS [P01 ES05622, P30 ES07048] NR 72 TC 30 Z9 32 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUL PY 2008 VL 29 IS 7 BP 1386 EP 1393 DI 10.1093/carcin/bgn136 PG 8 WC Oncology SC Oncology GA 335XX UT WOS:000258330000013 PM 18544563 ER PT J AU Hashizume, T Fukuda, T Nagaoka, T Tada, H Yamada, H Watanabe, K Salomon, DS Seno, M AF Hashizume, Toshihiro Fukuda, Takayuki Nagaoka, Tadahiro Tada, Hiroko Yamada, Hidenori Watanabe, Kazuhide Salomon, David S. Seno, Masaharu TI Cell type dependent endocytic internalization of ErbB2 with an artificial peptide ligand that binds to ErbB2 SO CELL BIOLOGY INTERNATIONAL LA English DT Article DE ErbB2; EC-1; Internalization; Endocytosis; SKBr3; SKOv3 ID EPIDERMAL-GROWTH-FACTOR; TUMOR NECROSIS FACTOR; DOWN-REGULATION; OVARIAN-CANCER; HUMAN-BREAST; MONOCLONAL-ANTIBODY; SIGNALING NETWORK; TYROSINE KINASES; FACTOR RECEPTOR; HER-2/NEU AB ErbB2, which is a member of the epidermal growth factor (erbB) receptor family, is frequently overexpressed in breast and ovarian cancers. Antibody and small molecule anti-tyrosine kinase inhibitors have been developed for targeted therapies for cancers overexpressing erbB2. Internalization and downregulation of erbB2, which is induced by a ligand, may be important for efficacious therapeutic effects. However, ligand-dependent erbB2 internalization has not been well characterized. Here we investigated the internalization of erbB2 in SKBr3 and SKOv3 cells, both overexpressing erbB2, using an EC-1 peptide fused to eGFP (EC-eGFP), which specifically binds to erbB2. ErbB2 was internalized in SKOv3 cells when the cells were treated with EC-eGFP. The accumulation of endosomal erbB2 was EC-eGFP dependent, which colocalized with transferrin implying endocytosis via clathrin-coated pits. In contrast, internalization of erbB2 was not observed in SKBr3 cells. As a result, two different mechanisms, which are cell type dependent for the internalization of erbB2, are proposed. (C) 2008 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved. C1 [Hashizume, Toshihiro; Fukuda, Takayuki; Nagaoka, Tadahiro; Tada, Hiroko; Yamada, Hidenori; Seno, Masaharu] Okayama Univ, Grad Sch Nat Sci & Technol, Dept Med Bioengn, Okayama 7008530, Japan. [Nagaoka, Tadahiro; Watanabe, Kazuhide; Salomon, David S.] NCI, Tumor Growth Factor Sect, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Seno, M (reprint author), Okayama Univ, Grad Sch Nat Sci & Technol, Dept Med Bioengn, 3-1-1 Tsushima Naka, Okayama 7008530, Japan. EM mseno@cc.okayama-u.ac.jp RI YAMADA, Hidenori/B-2639-2011; SENO, Masaharu /B-2092-2011; OI SENO, Masaharu /0000-0001-8547-6259; Nagaoka, Tadahiro/0000-0002-9391-0243 FU Ministry of Education, Culture, Sports, Science and Technology FX We thank Ms. N. Hironaka for the construction of the sErbB2 expression plasmid. We thank Ms. H. Sato for real-time quantitative PCR work. This research was supported by the Ministry of Education, Culture, Sports, Science and Technology Grant-in-Aid for Scientific Research. NR 45 TC 15 Z9 16 U1 1 U2 4 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1065-6995 J9 CELL BIOL INT JI Cell Biol. Int. PD JUL PY 2008 VL 32 IS 7 BP 814 EP 826 DI 10.1016/j.cellbi.2008.03.012 PG 13 WC Cell Biology SC Cell Biology GA 369CP UT WOS:000260671400014 PM 18442934 ER PT J AU Strizzi, L Abbott, DE Salomon, DS Hendrix, MJC AF Strizzi, Luigi Abbott, Daniel E. Salomon, David S. Hendrix, Mary J. C. TI Potential for cripto-1 in defining stem cell-like characteristics in human malignant melanoma SO CELL CYCLE LA English DT Article DE melanoma; nodal; cripto-1; lefty; tomoregulin; cerberus; oct4; nanog; cancer stem cells ID AMERICAN JOINT COMMITTEE; VERTEBRATE DEVELOPMENT; METASTATIC MELANOMA; TUMOR-CELLS; CANCER; PLURIPOTENCY; MICROENVIRONMENT; EXPRESSION; PLASTICITY; PHENOTYPE AB The diagnosis of melanoma is becoming ever more frequent. Although surgical excision of early lesions is associated with relatively significant high cure rates, treatment modalities are largely unsuccessful for advanced disease. Characteristics such as cellular heterogeneity and plasticity, expression of certain molecules such as the multidrug resistance protein-1 (MDR1) or the aberrant expression of embryonic signaling molecules and morphogens like Nodal, important for self renewal and pluripotency, suggest that a stem cell-like population may reside in aggressive melanomas. This perspective focuses on preliminary findings obtained in our laboratory which indicate that the expression of the Nodal coreceptor, Cripto-1, in a subset of malignant melanoma cells may be exploited to identify possible melanoma stem cells (MSC). In fact, the use of anti-Cripto-1 antibodies to cell sort Cripto-1-positive cells in the metastatic melanoma cell line C8161 has identified a slow growing, sphere forming subpopulation that expresses increased levels of Oct4, Nanog and MDR1. If current in vivo studies confirm the self renewal and tumorigenic characteristics of these cells, the expression of Cripto-1 may represent a useful marker to identify cancer stem cells in melanoma, and possibly other aggressive tumors as well. C1 [Strizzi, Luigi; Abbott, Daniel E.; Hendrix, Mary J. C.] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Childrens Mem Res Ctr, Chicago, IL 60614 USA. [Salomon, David S.] NCI, Mammary Biol & Tumorigenesis Lab, Bethesda, MD 20892 USA. RP Strizzi, L (reprint author), Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Childrens Mem Res Ctr, 2300 Childrens Plaza,Box 222, Chicago, IL 60614 USA. EM LStrizzi@childrensmemorial.org; MJCHendrix@childrensmemorial.org FU Intramural NIH HHS; NCI NIH HHS [R01 CA121205-02, R01 CA075681, CA75681, R37 CA059702-16, R37 CA059702, CA121205, CA59702, R01 CA059702, R01 CA075681-10, R01 CA121205] NR 42 TC 40 Z9 43 U1 0 U2 5 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JUL 1 PY 2008 VL 7 IS 13 BP 1931 EP 1935 DI 10.4161/cc.7.13.6236 PG 5 WC Cell Biology SC Cell Biology GA 323OX UT WOS:000257457200008 PM 18604175 ER PT J AU Ha, LN Merlino, G Sviderskaya, EV AF Ha, Linan Merlino, Glenn Sviderskaya, Elena V. TI Melanomagenesis - Overcoming the barrier of melanocyte senescence SO CELL CYCLE LA English DT Review DE senecence; melanoma; Ink4-Arf; p53; E2F1 ID TUMOR-SUPPRESSOR LOCUS; CELLULAR SENESCENCE; HUMAN CANCER; INK4A LOCUS; HUMAN-CELLS; P53; P16(INK4A); MICE; ARF; IMMORTALIZATION AB Although melanoma ultimately progresses to a highly aggressive and metastatic disease that is typically resistant to currently available therapy, it often begins as a benign nevus consisting of a clonal population of hyperplastic melanocytes that cannot progress because they are locked in a state of cellular senescence. Once senescence is overcome, the nevus can exhibit dysplastic features and readily progress to more lethal stages. Recent advances have convincingly demonstrated that senescence represents a true barrier to the progression of many types of cancer, including melanoma. Thus, understanding the mechanism(s) by which melanoma evades senescence has become a priority in the melanoma research community. Senescence in most cells is regulated through some combination of activities within the RB and p53 pathways. However, differences discovered among various tumor types, some subtle and others quite profound, have revealed that senescence frequently operates in a context-dependent manner. Here we review what is known about melanocyte senescence, and how such knowledge may provide a much-needed edge in our struggles to contain or perhaps vanquish this often-fatal malignancy. C1 [Sviderskaya, Elena V.] St Georges Univ London, Ctr Mol & Metab Signalling, Div Basic Med Sci, London SW17 0RE, England. [Ha, Linan] US FDA, Div Monoclonal Antibody, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. [Merlino, Glenn] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. RP Sviderskaya, EV (reprint author), St Georges Univ London, Ctr Mol & Metab Signalling, Div Basic Med Sci, Cranmer Terrace, London SW17 0RE, England. EM esviders@sgul.ac.uk RI Sviderskaya, Elena/D-2419-2009 FU Intramural NIH HHS [Z01 BC008756-20]; Wellcome Trust [078327] NR 65 TC 33 Z9 34 U1 1 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PD JUL 1 PY 2008 VL 7 IS 13 BP 1944 EP 1948 DI 10.4161/cc.7.13.6230 PG 5 WC Cell Biology SC Cell Biology GA 323OX UT WOS:000257457200010 PM 18604170 ER PT J AU Hollenberg, AN Forrest, D AF Hollenberg, Anthony N. Forrest, Douglas TI The thyroid and metabolism: The action continues SO CELL METABOLISM LA English DT Review ID HORMONE; RECEPTOR; CHOLESTEROL; TRANSPORTER; ACTIVATION; MUTATIONS; MICE AB On March 27, 2008, the American Thyroid Association sponsored a research summit on the Thyroid and Metabolism. The goals of the summit were to explore emerging new concepts and potential therapies arising from recent insights into the action of thyroid hormone signaling. New advances have identified functions previously thought to be distinct from thyroid hormone signaling pathways and suggest new avenues of therapy for metabolic disease. C1 [Forrest, Douglas] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. [Hollenberg, Anthony N.] Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA. [Hollenberg, Anthony N.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Forrest, D (reprint author), NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. EM thollenb@bidmc.harvard.edu FU Intramural NIH HHS; NIDDK NIH HHS [DK-56123, DK-078090] NR 12 TC 16 Z9 16 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD JUL PY 2008 VL 8 IS 1 BP 10 EP 12 DI 10.1016/j.cmet.2008.06.008 PG 3 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 321XK UT WOS:000257339600005 PM 18590688 ER PT J AU Sakaguchi, H Tokita, J Naoz, M Bowen-Pope, D Gov, NS Kachar, B AF Sakaguchi, Hirofumi Tokita, Joshua Naoz, Moshe Bowen-Pope, Daniel Gov, Nir S. Kachar, Bechara TI Dynamic compartmentalization of protein tyrosine phosphatase receptor Q at the proximal end of stereocilia: Implication of myosin VI-based transport SO CELL MOTILITY AND THE CYTOSKELETON LA English DT Article DE membrane protein; cargo transport; hair cells; cell surface coat; tapered base; myosin motors ID AUDITORY HAIR BUNDLES; ANKLE-LINK COMPLEX; INNER-EAR; PHOSPHATIDYLINOSITOL PHOSPHATASE; MEMBRANE PROTRUSIONS; MOLECULAR TREADMILL; CELL-SURFACE; PROTOCADHERIN-15; TRANSLOCATION; TRANSDUCTION AB Hair cell stereocilia are apical membrane protrusions filled with uniformly polarized actin filament bundles. Protein tyrosine phosphatase receptor Q (PTPRQ), a membrane protein with extracellular fibronectin repeats has been shown to localize at the stereocilia base and the apical hair cell surface, and to be essential for stereocilia integrity. We analyzed the distribution of PTPRQ and a possible mechanism for its compartmentalization. Using immunofluorescence we demonstrate that PTPRQ is compartmentalized at the stereocilia base with a decaying gradient from base to apex. This distribution can be explained by a model of transport directed toward the stereocilia base, which counteracts diffusion of the molecules. By mathematical analysis, we show that this counter transport is consistent with the minus end-directed movement of myosin VI along the stereocilia actin filaments. Myosin VI is localized at the stereocilia base, and exogenously expressed myosin VI and PTPRQ colocalize in the perinuclear endosomes in COS-7 cells. In myosin VI-deficient mice, PTPRQ is distributed along the entire stereocilia. PTPRQ-deficient mice show a pattern of stereocilia disruption that is similar to that reported in myosin VI-deficient mice, where the predominant features are loss of tapered base, and fusion of adjacent stereocilia. Thin section and freeze-etching electron microscopy showed that localization of PTPRQ coincides with the presence of a dense cell surface coat. Our results suggest that PTPRQ and myosin VI form a complex that dynamically maintains the organization of the cell surface coat at the stereocilia base and helps maintain the structure of the overall stereocilia bundle. C1 [Sakaguchi, Hirofumi; Tokita, Joshua; Kachar, Bechara] NIDCD, Sect Struct Cell Biol, Natl Inst Hlth, Bethesda, MD 20892 USA. [Sakaguchi, Hirofumi] Kyoto Prefectural Univ Med, Dept Otolaryngol Head & Neck Surg, Kyoto, Japan. [Naoz, Moshe; Gov, Nir S.] Weizmann Inst Sci, Dept Chem Phys, IL-76100 Rehovot, Israel. [Bowen-Pope, Daniel] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. RP Sakaguchi, H (reprint author), NIDCD, Sect Struct Cell Biol, Natl Inst Hlth, 50 S Dr,Rm 4249, Bethesda, MD 20892 USA. EM hiro-s@koto.kpu-m.ac.jp FU Intramural NIH HHS NR 32 TC 34 Z9 34 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0886-1544 J9 CELL MOTIL CYTOSKEL JI Cell Motil. Cytoskeleton PD JUL PY 2008 VL 65 IS 7 BP 528 EP 538 DI 10.1002/cm.20275 PG 11 WC Cell Biology SC Cell Biology GA 323YU UT WOS:000257485300002 PM 18412156 ER PT J AU Xie, H Gu, XX AF Xie, Hang Gu, Xin-Xing TI Moraxella catarrhalis lipooligosaccharide selectively upregulates ICAM-1 expression on human monocytes and stimulates adjacent naive monocytes to produce TNF-alpha through cellular cross-talk SO CELLULAR MICROBIOLOGY LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; NECROSIS-FACTOR-ALPHA; RESPIRATORY EPITHELIAL-CELLS; NONTYPABLE HAEMOPHILUS-INFLUENZAE; NF-KAPPA-B; OTITIS-MEDIA; SYNCYTIAL VIRUS; AIRWAY INFLAMMATION; SIGNAL-TRANSDUCTION; GENE POLYMORPHISMS AB To elucidate the role of Moraxella catarrhalis lipooligosaccharide (LOS) in otitis media with effusion (OME), the effects of LOS on adhesion antigens of human monocytes were investigated. M. catarrhalis LOS selectively enhanced intercellular adhesion molecule 1 (ICAM-1 or CD54) expression on human monocytes by significantly increasing both the surface expression intensity and the percentage of ICAM-1(+) cells. ICAM-1 upregulation on human monocytes by the LOS required surface CD14, TLR4, NF-kappa B p65 and c-Jun N-terminal kinase (JNK) activity. Our study also revealed that the LOS-induced surface ICAM-1 expression was partially mediated through a TNF-alpha dependent autocrine mechanism and could be further augmented by lipopolysaccharide-binding protein in serum. In addition, M. catarrhalis LOS also stimulated human monocytes to produce pro-inflammatory cytokines in both TLR4- and CD14-dependent pathways. Our results also indicated that enhanced surface ICAM-1 expression on monocytes may hinder their adherence to the lung epithelial monolayer. Furthermore, the LOS-activated human monocytes secreted a significantly high level of IL-8, and could stimulate adjacent naive monocytes to produce TNF-alpha which was partially mediated via membrane ICAM-1 and IL-8/IL-8RA. These results suggest that M. catarrhalis LOS could induce excessive middle ear inflammation through a cellular cross-talk mechanism during OME. C1 [Xie, Hang; Gu, Xin-Xing] Natl Inst Deafness & Other Commun Disorders, Vaccine Res Sect, Natl Inst Hlth, Rockville, MD 20850 USA. RP Gu, XX (reprint author), Natl Inst Deafness & Other Commun Disorders, Vaccine Res Sect, Natl Inst Hlth, Rockville, MD 20850 USA. EM guxx@nidcd.nih.gov FU Intramural NIH HHS NR 53 TC 15 Z9 15 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD JUL PY 2008 VL 10 IS 7 BP 1453 EP 1467 DI 10.1111/j.1462-5822.2008.01138.x PG 15 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 312QL UT WOS:000256685800006 PM 18363879 ER PT J AU Wang, YZ Schnetz-Boutaud, NC Kroth, H Yagi, H Sayer, JM Kurnar, S Jerina, DM Stone, MP AF Wang, Yazhen Schnetz-Boutaud, Nathalie C. Kroth, Heiko Yagi, Haruhiko Sayer, Jane M. Kurnar, Subodh Jerina, Donald M. Stone, Michael P. TI 3 '-intercalation of a N-2-dG 1R-trans-anti-Benzo[c]phenanthrene DNA adduct in an iterated (CG)(3) repeat SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID SALMONELLA-TYPHIMURIUM HISD3052; RESTRAINED MOLECULAR-DYNAMICS; (CPG)(3) FRAMESHIFT HOTSPOT; REGION DIOL-EPOXIDES; BENZOPHENANTHRENE 3,4-DIOL 1,2-EPOXIDES; RECONSTITUTED CYTOCHROME-P-450 SYSTEM; MALONDIALDEHYDE DEOXYGUANOSINE ADDUCT; POLYCYCLIC AROMATIC-HYDROCARBONS; TUMOR-INITIATING ACTIVITY; TEMPLATE-PRIMER JUNCTION AB The conformation of the 1R,2S,3R,4S-benzo[c]phenanthrene-N-2-dG adduct, arising from trans opening of the (+)-1S,2R,3R,4S-anti-benzo[c]phenanthrene diol epoxide, was examined in 5'-d(ATCGCXCG-GCATG)-3'-5'-d(CATGCCGCGCGAT)-3', where X = 1R,2S,3R,4S-B[c]P-N-2-dG. This duplex, derived from the hisD3052 frameshift tester strain of Salmonella typhimurium, contains a (CG)(3) iterated repeat, a hotspot for frameshift mutagenesis. NMR experiments showed a disconnection in sequential NOE connectivity between X-4 and C-5, and in the complementary strand, they showed another disconnection between G(18) and C-19. In the imino region of the H-1 NMR spectrum, a resonance was observed at the adducted base pair X-4 center dot C-19. The X-4 N1H and G(18) N1H resonances shifted upfield as compared to the other guanine imino proton resonances. NOEs were observed between X-4 N1H and C-19 (NH)-H-4 and between C-5 (NH)-H-4 and G(18) N1H, indicating that base pairs X-4 center dot C-19 and C-5 center dot G(18) maintained Watson-Crick hydrogen bonding. No NOE connectivity was observed between X4 and G18 in the imino region of the spectrum. Chemical shift perturbations of greater than 0.1 ppm were localized at nucleotides X-4 and C-5 in the modified strand and G 18 and C19 in the complementary strand. A total of 13 NOEs between the protons of the 1R-B[c]Ph moiety and the DNA were observed between B[c]Ph and major groove aromatic or amine protons at base pairs X-4 center dot C-19 and 3'-neighbor C-5 center dot G(18). Structural refinement was achieved using molecular dynamics calculations restrained by interproton distances and torsion angle restraints obtained from NMR data. The B[c]Ph moiety intercalated on the 3'-face of the X-4 center dot C-19 base pair such that the terminal ring of 1R-B[c]Ph threaded the duplex and faced into the major groove. The torsion angle alpha' [X-4] -N3-C2-N2-B[c]Ph]-C1 was calculated to be -177 degrees, maintaining an orientation in which the X-4 exocyclic amine remained in plane with the purine. The torsion angle beta'[X-4] -C2-N2[B[c]Ph]-C1-C2 was calculated to be 75 degrees. This value governed the 3'-orientation of the B[c]Ph moiety with respect to X-4. The helical rise between base pairs X-4 center dot C-19 and C-5 center dot G(18) increased and resulted in unwinding of the right-handed helix. The aromatic rings of the B[c]Ph moiety were below the Watson-Crick hydrogen-bonding face of the modified base pair X-4 center dot C-19. The B[c]Ph moiety was stacked above nucleotide G(18), in the complementary strand. C1 [Stone, Michael P.] Vanderbilt Univ, Dept Chem, Ctr Mol Toxicol, Nashville, TN 37235 USA. Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN 37235 USA. [Kroth, Heiko; Yagi, Haruhiko; Sayer, Jane M.; Jerina, Donald M.] NIDDK, Bioorgan Chem Lab, Natl Inst Hlth, DHHS, Bethesda, MD 20892 USA. [Kurnar, Subodh] SUNY Coll Buffalo, Environm Toxicol & Chem Lab, Great Lakes Ctr, Buffalo, NY 14222 USA. RP Stone, MP (reprint author), Vanderbilt Univ, Dept Chem, Ctr Mol Toxicol, Box 1583, Nashville, TN 37235 USA. EM michael.p.stone@vanderbilt.edu FU Intramural NIH HHS; NCI NIH HHS [CA-55678, CA-68485, P30 CA068485, R01 CA055678, R01 CA055678-16]; NCRR NIH HHS [RR-05805]; NIEHS NIH HHS [P01 ES005355, ES-00267, ES-05355, P01 ES005355-100003, P30 ES000267] NR 89 TC 5 Z9 5 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JUL PY 2008 VL 21 IS 7 BP 1348 EP 1358 DI 10.1021/tx7004103 PG 11 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 329IG UT WOS:000257860700009 PM 18549249 ER PT J AU Comin, MJ Vu, BC Boyer, PL Liao, C Hughes, SH Marquez, VE AF Comin, Maria J. Vu, B. Christie Boyer, Paul L. Liao, Chenzhong Hughes, Stephen H. Marquez, Victor E. TI D-(+)-iso-methanocarbathymidine: A high-affinity substrate for herpes simplex virus 1 thymidine kinase SO CHEMMEDCHEM LA English DT Article DE antiviral agents; asymmetric synthesis; carbocyclic nucleosides; enantiomers; HSV thymidine kinase ID CARBOCYCLIC NUCLEOSIDES; ANALOGS AB The stereoselective syntheses of the (+)-D and (-)-L enantiomers of iso-methanocarbathymidine (iso-MCT) was achieved through two independent linear approaches that converged on two antipodal enantiomers, common to a key precursor used in the synthesis of racemic iso-MCT In the study reported herein we identified (+)-3 [D-(+)-iso-MCT] as the active enantiomer that was exclusively recognized by the herpes simplex virus 1 thymidine kinase (HSV1-tk), as was predicted by molecular modeling. For this purpose, a human osteosarcoma (HOS) cell line modified to contain and express HSV1-tk from herpes simplex virus 1 (HSV1) was used to determine the cytotoxicity of the compounds by an assay that measures the level of ATP in the cells. The work demonstrates that changes in the substitution pattern of rigid bicyclo[3.1.0]hexane nucleosides, which, relative to normal nucleosides, appear unconventional, can lead to the spatial optimization of pharmacophores and vastly improved substrate recognition. C1 [Comin, Maria J.; Liao, Chenzhong; Marquez, Victor E.] Natl Canc Inst, Ctr Canc Res, Med Chem Lab, Frederick, MD 21702 USA. [Vu, B. Christie; Boyer, Paul L.; Hughes, Stephen H.] Natl Canc Inst, Ctr Canc Res, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Marquez, VE (reprint author), Natl Canc Inst, Ctr Canc Res, Med Chem Lab, POB B,Bldg 376, Frederick, MD 21702 USA. EM marquezv@mail.nih.gov FU Intramural NIH HHS [Z01 BC006174-22] NR 10 TC 7 Z9 7 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1860-7179 J9 CHEMMEDCHEM JI ChemMedChem PD JUL PY 2008 VL 3 IS 7 BP 1129 EP 1134 DI 10.1002/cmdc.200800027 PG 6 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 328TS UT WOS:000257821300016 PM 18399509 ER PT J AU Steffen-Smith, EA Wolters, PL Albert, PS Baker, EH Shimoda, KC Barnett, AS Warren, KE AF Steffen-Smith, Emilie A. Wolters, Pamela L. Albert, Paul S. Baker, Eva H. Shimoda, Kim C. Barnett, Alan S. Warren, Katherine E. TI Detection and characterization of neurotoxicity in cancer patients using proton MR spectroscopy SO CHILDS NERVOUS SYSTEM LA English DT Article DE MRI; MRS; primary brain tumor; pediatric; neuropsychological assessment ID MAGNETIC-RESONANCE-SPECTROSCOPY; ACUTE LYMPHOBLASTIC-LEUKEMIA; SJOGREN-LARSSON-SYNDROME; LONG-TERM SURVIVORS; WHITE-MATTER; CRANIAL IRRADIATION; COGNITIVE FUNCTION; CHILDHOOD-CANCER; BRAIN-TUMORS; CHILDREN AB Objective The study objective was to detect abnormalities and identify relationships between brain metabolic ratios determined by proton magnetic resonance spectroscopic imaging ((1)H-MRSI) and neuropsychological (NP) function in cancer patients at risk for neurotoxicity. Methods Thirty-two patients received (1)H-MRSI using a multi-slice, multi-voxel technique on a 1.5T magnet. Cho/NAA, NAA/Cr, and Cho/Cr ratios were identified in seven pre-determined sites without tumor involvement. A battery of age-appropriate NP tests was administered within 7 days of imaging. Relationships were examined between test scores and metabolite ratios. Conclusions This study identifies relationships between brain metabolite ratios and cognitive functioning in cancer patients. (1)H-MRSI may be useful in early detection of neurotoxic effects, but prospective longitudinal studies in a homogeneous population are recommended to determine the prognostic value. C1 [Warren, Katherine E.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Steffen-Smith, Emilie A.; Wolters, Pamela L.; Warren, Katherine E.] NCI, NIH, Canc Res Ctr, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Wolters, Pamela L.] Med Illness Counseling Ctr, Chevy Chase, MD USA. [Albert, Paul S.] NCI, NIH, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Baker, Eva H.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Shimoda, Kim C.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Barnett, Alan S.] NIMH, NIH, CBDB, Bethesda, MD 20892 USA. RP Warren, KE (reprint author), NCI, Pediat Oncol Branch, Bldg 10-Room 1-3940,9000 Rockville Pike, Bethesda, MD 20892 USA. EM warrenk@mail.nih.gov OI Steffen-Smith, Emilie/0000-0002-4966-3046 FU Intramural NIH HHS [Z01 BC010581-03]; NCI NIH HHS [N01-SC-71102, N01-SC-07006]; PHS HHS [HHSN261200477004C] NR 44 TC 8 Z9 8 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0256-7040 J9 CHILD NERV SYST JI Childs Nerv. Syst. PD JUL PY 2008 VL 24 IS 7 BP 807 EP 813 DI 10.1007/s00381-007-0576-2 PG 7 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA 306RA UT WOS:000256264300004 PM 18293002 ER PT J AU Butler, J Kalogeropoulos, A Georgiopoulou, V Belue, R Rodondi, N Garcia, M Bauer, DC Satterfield, S Smith, AL Vaccarino, V Newman, AB Harris, TB Wilson, PWF Kritchevsky, SB AF Butler, Javed Kalogeropoulos, Andreas Georgiopoulou, Vasiliki Belue, Rhonda Rodondi, Nicolas Garcia, Melissa Bauer, Douglas C. Satterfield, Suzanne Smith, Andrew L. Vaccarino, Viola Newman, Anne B. Harris, Tamara B. Wilson, Peter W. F. Kritchevsky, Stephen B. CA Health ABC Study TI Incident Heart Failure Prediction in the Elderly The Health ABC Heart Failure Score SO CIRCULATION-HEART FAILURE LA English DT Article DE heart failure; elderly; risk factors; statistical models; epidemiology ID RISK-FACTORS; GENERAL-POPULATION; COMMUNITY; SURVIVAL; DISEASE; MODELS; MEN; HOSPITALIZATION; HYPERTENSION; ASSOCIATION AB Background-Despite the rising heart failure (HF) incidence and aging United States population, there are no validated prediction models for incident HF in the elderly. We sought to develop a new prediction model for 5-year risk of incident HF among older persons. Methods and Results-Proportional hazards models were used to assess independent predictors of incident HF, defined as hospitalization for new-onset HF, in 2935 elderly participants without baseline HF enrolled in the Health ABC study (age, 73.6 +/- 2.9 years, 47.9% males, 58.6% whites). A prediction equation was developed and internally validated by bootstrapping, allowing the development of a 5-year risk score. Incident HF developed in 258 (8.8%) participants during 6.5 +/- 1.8 years of follow-up. Independent predictors of incident HF included age, history of coronary disease and smoking, baseline systolic blood pressure and heart rate, serum glucose, creatinine. and albumin levels, and left ventricular hypertrophy. The Health ABC HF model had a c-statistic of 0.73 in the derivation dataset, 0.72 by internal validation (optimism-corrected), and good calibration (goodness-of-fit chi(2) 6.24, P=0.621). A simple point score was created to predict incident HF risk into 4 risk groups corresponding to <5%, 5% to 10%, 10% to 20%, and >20% 5-year risk. The actual 5-year incident HF rates in these groups were 2.9%. 5.7%. 13.3%, and 36.8%, respectively. Conclusion-The Health ABC HF prediction model uses common clinical variables to predict incident HF risk in the elderly, an approach that may be used to target and treat high-risk individuals. (Circ Heart Fail. 2008;1:125-133.) C1 [Butler, Javed; Kalogeropoulos, Andreas; Georgiopoulou, Vasiliki; Smith, Andrew L.; Vaccarino, Viola; Wilson, Peter W. F.] Emory Univ, Atlanta, GA 30322 USA. [Belue, Rhonda] Penn State Univ, Hershey, PA USA. [Rodondi, Nicolas] Univ Lausanne, Lausanne, Switzerland. [Garcia, Melissa] NIA, NIH, Bethesda, MD 20892 USA. [Bauer, Douglas C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Satterfield, Suzanne] Univ Memphis, Memphis, TN 38152 USA. [Newman, Anne B.] Univ Pittsburgh, Pittsburgh, PA USA. [Kritchevsky, Stephen B.] Wake Forest Univ, Winston Salem, NC 27109 USA. RP Butler, J (reprint author), Emory Univ Hosp, Div Cardiol, 1365 Clifton Rd NE,Suite AT430, Atlanta, GA 30322 USA. EM javed.butler@emory.edu RI Kalogeropoulos, Andreas/A-9494-2009; Newman, Anne/C-6408-2013; OI Kalogeropoulos, Andreas/0000-0002-1284-429X; Newman, Anne/0000-0002-0106-1150; Kritchevsky, Stephen/0000-0003-3336-6781 FU Intramural Research Program; National Institute of Aging; National Institutes of Health, Bethesda [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106.] FX This research was supported in part by the Intramural Research Program of the National Institute of Aging, National Institutes of Health, Bethesda, Md, and by grants N01-AG-6-2101, N01-AG-6-2103. and N01-AG-6-2106. NR 42 TC 100 Z9 100 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD JUL PY 2008 VL 1 IS 2 BP 125 EP 133 DI 10.1161/CIRCHEARTFAILURE.108.768457 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 446NF UT WOS:000266127600007 PM 19777072 ER PT J AU Reveille, JD Sims, AM Maksymowych, WP Ward, MM Stone, MA Rahman, P Weisman, MH Inman, RD Gladman, DD Davis, JC Learch, TJ Savage, L Diekman, L Danoy, P Pointon, JJ Zhou, X Evans, D Wordsworth, BP Brown, MA AF Reveille, J. D. Sims, A. M. Maksymowych, W. P. Ward, M. M. Stone, M. A. Rahman, P. Weisman, M. H. Inman, R. D. Gladman, D. D. Davis, J. C. Learch, T. J. Savage, L. Diekman, L. Danoy, P. Pointon, J. J. Zhou, X. Evans, D. Wordsworth, B. P. Brown, M. A. TI Genomewide association study in ankylosing spondylitis identifies major non-MHC genetic determinants of disease susceptibility SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Meeting Abstract C1 [Reveille, J. D.; Diekman, L.; Zhou, X.] Univ Texas Houston, Houston, TX USA. [Sims, A. M.; Danoy, P.; Brown, M. A.] Univ Queensland, Brisbane, Qld, Australia. [Maksymowych, W. P.] Univ Alberta, Edmonton, AB, Canada. [Ward, M. M.] NIAMS, Intramural Res Program, Bethesda, MD USA. [Stone, M. A.] RNHRD, Bath, Avon, England. [Rahman, P.] Mem Univ Newfoundland, St John, NF, Canada. [Weisman, M. H.; Learch, T. J.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Inman, R. D.; Gladman, D. D.] Toronto Western Hosp, Toronto, ON M5T 2S8, Canada. [Davis, J. C.] UCSF, San Francisco, CA USA. [Savage, L.] Spondylitis Assn Amer, Sherman Oaks, CA USA. [Pointon, J. J.; Wordsworth, B. P.] Univ Oxford, Oxford OX1 2JD, England. [Evans, D.] Univ Bristol, Bristol, Avon, England. NR 0 TC 1 Z9 1 U1 0 U2 0 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD JUL-AUG PY 2008 VL 26 IS 4 BP 723 EP 723 PG 1 WC Rheumatology SC Rheumatology GA 349IX UT WOS:000259275600075 ER PT J AU Higgins, J Metcalf, JA Stevens, RA Baseler, M Proschan, M Lane, HC Sereti, I AF Higgins, Jeanette Metcalf, Julia A. Stevens, Randy A. Baseler, Michael Proschan, Michael Lane, H. Clifford Sereti, Irini TI Effects of delays in peripheral blood processing, including cryopreservation, on detection of CD31 expression on naive CD4 T cells SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID FLOW-CYTOMETRY; MONONUCLEAR-CELLS; WHOLE-BLOOD; SUBSETS; PECAM-1; ADULTS AB Delayed processing of peripheral blood or peripheral blood mononuclear cell isolation and cryopreservation can lead to the detection of somewhat higher levels of CD31 expression on naive CD4 T cells by flow cytometry. These observations should be considered in the planning of multicenter clinical trials and in the interpretation of the results of functional studies. C1 [Metcalf, Julia A.; Proschan, Michael; Lane, H. Clifford; Sereti, Irini] NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Higgins, Jeanette; Stevens, Randy A.; Baseler, Michael] NCI, AIDS Monitoring Lab, Clin Serv Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Sereti, I (reprint author), NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, NIH, Bldg 10,Room 11B-04,10 Ctr Dr,MSC 1876, Bethesda, MD 20892 USA. EM isereti@niaid.nih.gov FU National Cancer Institute, National Institutes of Health [NO1-CO-12400] 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 NO1-CO-12400. NR 13 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD JUL PY 2008 VL 15 IS 7 BP 1141 EP 1143 DI 10.1128/CVI.00430-07 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 340TE UT WOS:000258667100017 PM 18448620 ER PT J AU Allen, C Saigal, K Nottingham, L Arun, P Chen, Z Van Waes, C AF Allen, Clint Saigal, Kunal Nottingham, Liesl Arun, Pattatheyil Chen, Zhong Van Waes, Carter TI Bortezomib-induced apoptosis with limited clinical response is accompanied by inhibition of canonical but not alternative nuclear factor-kappa B subunits in head and neck cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; PROINFLAMMATORY CYTOKINE EXPRESSION; GROWTH-FACTOR RECEPTOR; TUMOR-GROWTH; CONSTITUTIVE ACTIVATION; THERAPEUTIC TARGET; KINASE; TRANSCRIPTION; PROGRESSION; PATHWAY AB Purpose: Nuclear factor-kappa B (NF-kappa B)/REL transcription factors promote cancer cell survival and progression. The canonical (NF-kappa B1/RELA or cREL) and alternate (NF-kappa B2/RELB) pathways require the proteasome for cytoplasmic-nuclear translocation, prompting the investigation of bortezomib for cancer therapy. However, limited clinical activity of bortezomib has been observed in many epithelial malignancies, suggesting this could result from incomplete inhibition of NF-kappa B/RELs or other prosurvival signal pathways. Experimental Design: To examine these possibilities, matched biopsies from 24 h posttreatment were obtained from accessible tumors of patients who received low-dose bortezomib (0.6 mg/m(2)) before reirradiation in a phase 1 trial for recurrent head and neck squamous cell carcinoma (HNSCC). Effects of bortezomib on apoptosis and proliferation by TUNEL and Ki67 staining were compared with nuclear staining for all five NF-kappa B subunits, phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2), and phosphorylated signal transducers and activators of transcription 3 (STAT3) in tumor biopsies, and by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTP) and DNA binding assay for the five NF-kappa B subunits in HNSCC cell lines. Results: HNSCC showed increased nuclear staining for all five NF-kappa B subunits, phosphorylated ERK1/2, and phosphorylated STAT3. Bortezomib treatment significantly enhanced apoptosis with inhibition of nuclear RELA in three of four tumors, but other NF-kappa B subunits, ERK1/2, and STAT3 were variably or not affected, and tumor progression was observed within 3 months. In HNSCC cell lines, 10-8 mol/L bortezomib inhibited cell density while inhibiting tumor necrosis factor-alpha-induced and partially inhibiting basal activation of NF-kappa B1/RELA, but not NF-kappa B2/RELB. Conclusions: Although low-dose bortezomib inhibits activation of subunits of the canonical pathway, it does not block nuclear activation of the noncanonical NF-kappa B or other prosurvival signal pathways, which may contribute to the heterogeneous responses observed in HNSCC. C1 [Allen, Clint; Saigal, Kunal; Nottingham, Liesl; Arun, Pattatheyil; Chen, Zhong; Van Waes, Carter] Natl Inst Deafness & Other Commun Disorders, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD USA. RP Van Waes, C (reprint author), 10 Ctr Dr CRC,Room 4-2732M, Bethesda, MD 20892 USA. EM vanwaesc@nidcd.nih.gov FU Intramural NIH HHS NR 42 TC 53 Z9 56 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL 1 PY 2008 VL 14 IS 13 BP 4175 EP 4185 DI 10.1158/1078-0432.CCR-07-4470 PG 11 WC Oncology SC Oncology GA 322LT UT WOS:000257377300021 PM 18593997 ER PT J AU Gardner, ER Dahut, WL Scripture, CD Jones, J Aragon-Ching, JB Desai, N Hawkins, MJ Sparreboom, A Figg, WD AF Gardner, Erin R. Dahut, William L. Scripture, Charity D. Jones, Jacquin Aragon-Ching, Jeanny B. Desai, Neil Hawkins, Michael J. Sparreboom, Alex Figg, William D. TI Randomized crossover pharmacokinetic study of solvent-based paclitaxel and nab-paclitaxel SO CLINICAL CANCER RESEARCH LA English DT Article ID ALBUMIN-BOUND PACLITAXEL; UNBOUND PACLITAXEL; CREMOPHOR-FREE; BREAST-CANCER; HUMAN PLASMA; ABI-007; FORMULATION; EL; CHEMOTHERAPY; FRACTION AB Purpose: Abraxane (ABI-007) is a 130-nm albumin-bound (nab) particle formulation of paclitaxel, devoid of any additional excipients. We hypothesized that this change in formulation alters the systemic disposition of paclitaxel compared with conventional solvent-based formulations (sb-paclitaxel; Taxol), and leads to improved tolerability of the drug. Patients and Methods: Patients with malignant solid tumors were randomized to receive the recommended single-agent dose of nab-paclitaxel (260 mg/m(2) as a 30-minute infusion) or sb-paclitaxel (175 mg/m(2) as a 3-hour infusion). After cycle 1, patients crossed over to the alternate treatment. Pharmacokinetic studies were carried out for the first cycle of sb-paclitaxel and the first two cycles of nab-paclitaxel. Results: Seventeen patients were treated, with 14 receiving at least one cycle each of nab-paclitaxel and sb-paclitaxel. No change in nab-paclitaxel pharmacokinetics was found between the first and second cycles (P = 0.95), suggesting limited intrasubject variability. Total drug exposure was comparable between the two formulations (P =. 0.55) despite the dose difference. However, exposure to unbound paclitaxel was significantly higher after nab-paclitaxel administration, due to the increased free fraction (0.063 +/- 0.021 versus 0.024 +/- 0.009; P < 0.001). Conclusion: This study shows that paclitaxel disposition is subject to considerable variability depending on the formulation used. Because systemic exposure to unbound paclitaxel is likely a driving force behind tumoral uptake, these findings explain, at least in part, previous observations that the administration of nab-paclitaxel is associated with augmented antitumor efficacy compared with solvent-based paclitaxel. C1 [Dahut, William L.; Scripture, Charity D.; Jones, Jacquin; Aragon-Ching, Jeanny B.; Sparreboom, Alex; Figg, William D.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Gardner, Erin R.] NCI, Clin Pharmacol Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21701 USA. [Desai, Neil; Hawkins, Michael J.] Abraxis BioSci Inc, Los Angeles, CA USA. RP Figg, WD (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016; OI Aragon-Ching, Jeanny/0000-0002-6714-141X FU Intramural NIH HHS [NIH0011335962, Z01 BC010548-02, Z01 SC006537-14, Z01 SC010098-08]; NCI NIH HHS [N01CO12400] NR 18 TC 89 Z9 93 U1 3 U2 16 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL 1 PY 2008 VL 14 IS 13 BP 4200 EP 4205 DI 10.1158/1078-0432.CCR-07-4592 PG 6 WC Oncology SC Oncology GA 322LT UT WOS:000257377300024 PM 18594000 ER PT J AU Chakraborty, M Wansley, EK Carrasquillo, JA Yu, S Paik, CH Camphausen, K Becker, MD Goeckeler, WF Schlom, J Hodge, JW AF Chakraborty, Mala Wansley, Elizabeth K. Carrasquillo, Jorge A. Yu, Sarah Paik, Chang H. Camphausen, Kevin Becker, Michael D. Goeckeler, William F. Schlom, Jeffrey Hodge, James W. TI The use of chelated radionuclide (samarium-153-ethylenediaminetetramethylenephosphonate) to modulate phenotype of tumor cells and enhance T cell-mediated killing SO CLINICAL CANCER RESEARCH LA English DT Article ID PROSTATE-SPECIFIC ANTIGEN; HUMAN CARCINOEMBRYONIC ANTIGEN; BONE METASTASES; ANTITUMOR IMMUNOTHERAPY; SKELETAL METASTASES; IONIZING-RADIATION; LYMPHOCYTE EPITOPE; IMMUNE ESCAPE; CANCER CELLS; EXPRESSION AB Purpose: Exposing human tumor cells to sublethal doses of external beam radiation up-regulates expression of tumor antigen and accessory molecules, rendering tumor cells more susceptible to killing by antigen-specific CTLs. This study explored the possibility that exposure to palliative doses of a radiopharmaceutical agent could alter the phenotype of tumor cells to render them more susceptible to T cell - mediated killing. Experimental Design: Here, 10 human tumor cell lines (4 prostate, 2 breast, and 4 lung) were exposed to increasing doses of the radiopharmaceutical samarium-153-ethylenediaminetetramethylenephosphonate (153 Sm-EDTMP) used in cancer patients to treat pain due to bone metastasis. Flu orescence-activated cell sorting analysis and quantitative real-time PCR analysis for expression of five surface molecules and several tumor-associated antigens involved in prostate cancer were done. LNCaP human prostate cancer cells were exposed to 1 53 Sm-EDTMP and incubated with tumor-associated antigen-specific CTL in a CTL killing assay to determine whether exposure to 153 Sm-EDTMP rendered LNCaP cells more susceptible to T cell - mediated killing. Results: Tumor cells up-regulated the surface molecules Fas (100% of cell lines up-regulated Fas), carcinoembryonic antigen (90%), mucin-1 (60%), MHC class 1 (50%), and intercellular adhesion molecule-1 (40%) in response to 153 Sm-EDTMP. Quantitative real-time PCR analysis revealed additional up-regulated tumor antigens. Exposure to 153 Sm-EDTMP rendered LNCaP cells more susceptible to killing by CTLs specific for prostate-specific antigen, carcinoembryonic antigen, and mucin-1. Conclusions: Doses of 153 Sm-EDTMP equivalent to palliative doses delivered to bone alter the phenotype of tumor cells, suggesting that 1 53 Sm-EDTMP may work synergistically with immunotherapy to increase the susceptibility of tumor cells to CTL killing. C1 [Chakraborty, Mala; Wansley, Elizabeth K.; Schlom, Jeffrey; Hodge, James W.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Yu, Sarah; Paik, Chang H.] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Camphausen, Kevin] NIH, Dept Nucl Med, Bethesda, MD 20892 USA. [Carrasquillo, Jorge A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B09, Bethesda, MD 20892 USA. EM js141c@nih.gov RI Carrasquillo, Jorge/E-7120-2010; Hodge, James/D-5518-2015; OI Hodge, James/0000-0001-5282-3154; Wansley, Elizabeth/0000-0002-0110-7550; Carrasquillo, Jorge/0000-0002-8513-5734 FU Intramural NIH HHS [Z01 SC010373-08] NR 53 TC 34 Z9 34 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL 1 PY 2008 VL 14 IS 13 BP 4241 EP 4249 DI 10.1158/1078-0432.CCR-08-0335 PG 9 WC Oncology SC Oncology GA 322LT UT WOS:000257377300030 PM 18594006 ER PT J AU Wansley, EK Chakraborty, M Hance, KW Bernstein, MB Boehm, AL Guo, ZM Quick, D Franzusoff, A Greiner, JW Schlom, J Hodge, JW AF Wansley, Elizabeth K. Chakraborty, Mala Hance, Kenneth W. Bernstein, Michael B. Boehm, Amanda L. Guo, Zhimin Quick, Deborah Franzusoff, Alex Greiner, John W. Schlom, Jeffrey Hodge, James W. TI Vaccination with a recombinant Saccharomyces cerevisiae expressing a tumor antigen breaks immune tolerance and elicits therapeutic antitumor responses SO CLINICAL CANCER RESEARCH LA English DT Article ID HUMAN CARCINOEMBRYONIC ANTIGEN; YEAST-BASED IMMUNOTHERAPY; T-LYMPHOCYTE RESPONSES; CEA TRANSGENIC MICE; DENDRITIC CELLS; INDUCTION; GENE AB Purpose: Saccharomyces cerevisiae, a nonpathogenic yeast, has been used previously as a vehicle to elicit immune responses to foreign antigens, and tumor-associated antigens, and has been shown to reduce tumor burden in mice. Studies were designed to determine if vaccination of human carcinoembryonic antigen (CEA)-transgenic (CEA-Tg) mice (where CEA is a self-antigen) with a recombinant S. cerevisiae construct expressing human CEA (yeast-CEA) elicits CEA-specific T-cell responses and antitumor activity. Experimental Design: CEA-Tg mice were vaccinated with yeast-CEA, and CD4(+) and CD8(+) T-cell responses were assessed after one and multiple administrations or vaccinations at multiple sites per administration. Antitumor activity was determined by tumor growth and overall survival in both pulmonary metastasis and s.c. pancreatic tumor models. Results: These studies demonstrate that recombinant yeast can break tolerance and that (a) yeast-CEA constructs elicit both CEA-specific CD4+ and CD8(+) T-cell responses; (b) repeated yeast-CEA administration causes increased antigen -specific T-cell responses after each vaccination; (c) vaccination with yeast-CEA at multiple sites induces a greater T-cell response than the same dose given at a single site; and (d) tumor-bearing mice vaccinated with yeast-CEA show a reduction in tumor burden and increased overall survival compared to mock-treated or control yeast-vaccinated mice in both pulmonary metastasis and s.c. pancreatic tumor models. Conclusions: Vaccination with a heat-killed recombinant yeast expressing the tumor-associated antigen CEA induces CEA-specific immune responses, reduces tumor burden, and extends overall survival in CEA-Tg mice. These studies thus form the rationale for the incorporation of recombinant yeast-CEA and other recombinant yeast constructs in cancer immunotherapy protocols. C1 [Wansley, Elizabeth K.; Chakraborty, Mala; Hance, Kenneth W.; Bernstein, Michael B.; Boehm, Amanda L.; Greiner, John W.; Schlom, Jeffrey; Hodge, James W.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Guo, Zhimin; Quick, Deborah; Franzusoff, Alex] Globelmmune Inc, Louisville, CO USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B09, Bethesda, MD 20892 USA. EM js141c@nih.gov RI Hodge, James/D-5518-2015; OI Hodge, James/0000-0001-5282-3154; Wansley, Elizabeth/0000-0002-0110-7550 FU Intramural NIH HHS [, Z01 BC010974-01]; NCI NIH HHS [Z01 BC010974-01] NR 30 TC 47 Z9 49 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL 1 PY 2008 VL 14 IS 13 BP 4316 EP 4325 DI 10.1158/1078-0432.CCR-08-0393 PG 10 WC Oncology SC Oncology GA 322LT UT WOS:000257377300039 PM 18594015 ER PT J AU Zonios, DI Gea-Banacloche, J Childs, R Bennett, JE AF Zonios, Dimitrios I. Gea-Banacloche, Juan Childs, Richard Bennett, John E. TI Hallucinations during voriconazole therapy SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID INVASIVE ASPERGILLOSIS; AMPHOTERICIN-B; MULTICENTER; FLUCONAZOLE; TRIAL AB As part of a prospective natural history cohort study of voriconazole toxicity, we describe the characteristics of 12 of 72 voriconazole-treated patients who experienced hallucinations from March 2006 through November 2007. Hallucinations associated with voriconazole use are not uncommon. Doctors should be aware of this complication, and the recipients of the drug should be reassured that the hallucinations are an effect of the drug. C1 [Zonios, Dimitrios I.; Bennett, John E.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Gea-Banacloche, Juan] NCI, NIH, Bethesda, MD 20892 USA. [Childs, Richard] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Bennett, JE (reprint author), 9000 Rockville Pike,Bldg 10,Rm 12C106, Bethesda, MD 20892 USA. EM jbennett@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000654-16] NR 12 TC 52 Z9 54 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL 1 PY 2008 VL 47 IS 1 BP E7 EP E10 DI 10.1086/588844 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 309BF UT WOS:000256434100034 PM 18491963 ER PT J AU Wang, XM Hamza, M Gordon, SM Wahl, SM Dionne, RA AF Wang, X-M Hamza, M. Gordon, S. M. Wahl, S. M. Dionne, R. A. TI COX inhibitors downregulate PDE4D expression in a clinical model of inflammatory pain SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID TUMOR-NECROSIS-FACTOR; TNF-ALPHA; GENE-EXPRESSION; PHOSPHODIESTERASE ACTIVITY; CAMP; INDOMETHACIN; HYPERALGESIA; ARTHRITIS; ROLIPRAM; PATHWAY AB Tumor necrosis factor-alpha (TNF-alpha) has a central role in inflammation and is modulated by prostaglandin E-2 (PGE(2)) and cyclic adenosine monophosphate (cAMP). Using microarray, quantitative real-time polymerase chain reaction (qRT-PCR), and protein detection techniques, we showed that ketorolac and rofecoxib had no significant effect on TNF-alpha gene expression in oral mucosal biopsies 3 h after surgery. They both, however, downregulated the gene and protein expression of phosphodiesterase type 4 (PDE4D), which might represent a novel mechanism contributing to their analgesic and anti-inflammatory effects. C1 [Wang, X-M; Hamza, M.; Dionne, R. A.] NINR, Pain Res Sect, NIH, Bethesda, MD 20892 USA. [Hamza, M.] Ain Shams Univ, Fac Med, Dept Pharmacol, Cairo, Egypt. [Gordon, S. M.] Univ Maryland, Sch Dent, Dept Biomed Sci, Baltimore, MD 21201 USA. [Wahl, S. M.] Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. RP Dionne, RA (reprint author), NINR, Pain Res Sect, NIH, Bethesda, MD 20892 USA. EM dionner@mail.nih.gov RI Hamza, May/A-5053-2010 OI Hamza, May/0000-0002-7637-3060 FU Intramural NIH HHS NR 29 TC 6 Z9 6 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JUL PY 2008 VL 84 IS 1 BP 39 EP 42 DI 10.1038/sj.clpt.6100501 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 314VN UT WOS:000256837400008 PM 18288087 ER PT J AU Knerr, I Gibson, KM Jakobs, C Pearl, PL AF Knerr, Ina Gibson, K. Michael Jakobs, Cornelis Pearl, Phillip L. TI Neuropsychiatric morbidity in adolescent and adult succinic semialdehyde dehydrogenase deficiency patients SO CNS SPECTRUMS LA English DT Article ID GAMMA-HYDROXYBUTYRIC ACIDURIA; CULTURED HUMAN-LYMPHOBLASTS; 4-HYDROXYBUTYRIC ACIDURIA; SSADH DEFICIENCY; MICE DEFICIENT; GABA-METABOLISM; KETOGENIC DIET; CLINICAL PHENOTYPE; VIGABATRIN THERAPY; MYELIN ALTERATIONS AB Introduction: Succinic semialdehyde dehydrogenase (SSADH) deficiency (gamma-hydroxybutyric aciduria) is a rare neurometabolic disorder of gamma-aminobutyric acid degradation. While neurological manifestations, such as developmental delay, are typical during infancy, limited data are available on adolescent and adult symptomatology. Methods: We overview the phenotype of 33 adolescents and adults (10.1-39.5 years of age, mean:17.1 years, 48% females) with SSADH deficiency. For this purpose, we applied a database with systematic questionnaire-based follow-up data. Results: Sixty-six percent of patients (n=21) presented by 6 months of age, 14% from 6-12 months of age, 5% from 1-2 years of age, and 14% from 2-4 years of age, mean age at first symptoms was 11 +/- 12 months. However, mean age at diagnosis was 6.6 +/- 6.4 years of age. Presenting symptoms encompassed motor delay, hypotonia, speech delay, autistic features, seizures, and ataxia. Eighty-two percent demonstrated behavioral problems, such as attention deficit, hyperactivity, anxiety, or aggression, and 33% had >= 3 behavior problems. Electroencephalograms showed background slowing or epileptiform discharges in 40% of patients. Treatment approaches are then summarized. Conclusion: The variable phenotype in SSADH deficiency suggests the likelihood that this disease may be under-diagnosed. Families of patients with SSADH deficiency should be counseled and supported regarding the anticipated persistence of various neuropsychiatric symptoms into adulthood. C1 [Gibson, K. Michael] Univ Pittsburgh, Div Med Genet, Med Ctr, Childrens Hosp Pittsburgh,Biochem Genet Lab, Pittsburgh, PA 15213 USA. [Knerr, Ina] Univ Erlangen Nurnberg, Childrens & Adolescents Hosp, Erlangen, Germany. [Gibson, K. Michael] Univ Pittsburgh, Sch Med, Dept Pediat, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. [Gibson, K. Michael] Univ Pittsburgh, Sch Med, Dept Pathol, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. [Gibson, K. Michael] Univ Pittsburgh, Sch Med, Dept Human Genet, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. [Jakobs, Cornelis] Vrije Univ Amsterdam Med Ctr, Dept Clin Chem, Metab Unit, Amsterdam, Netherlands. [Pearl, Phillip L.] George Washington Univ, Sch Med, Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20052 USA. [Pearl, Phillip L.] Natl Inst Neurol Disorders & Stroke, Clin Epilepsy Branch, Bethesda, MD USA. RP Gibson, KM (reprint author), Univ Pittsburgh, Div Med Genet, Med Ctr, Childrens Hosp Pittsburgh,Biochem Genet Lab, Rangos Res Bldg,Room 2111,3460 5th Ave, Pittsburgh, PA 15213 USA. EM Michael.Gibson@chp.edu FU National Institutes of Health [NS40270]; Pediatric Neurotransmitter Disease Association; SHS International; University of Erlangen-Nuremberg FX This study was supported in part by National Institutes of Health grant NS40270 awarded to Dr. Gibson, the Pediatric Neurotransmitter Disease Association (Drs. Pearl and Gibson), SHS International (Dr. Knerr), and the University of Erlangen-Nuremberg. NR 60 TC 24 Z9 25 U1 0 U2 0 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD JUL PY 2008 VL 13 IS 7 BP 598 EP 605 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 339OL UT WOS:000258586800012 PM 18622364 ER PT J AU Houston, D Costanzi, S Jacobson, KA Harden, TK AF Houston, Dayle Costanzi, Stefano Jacobson, Kenneth A. Harden, T. Kendall TI Development of selective high affinity antagonists, agonists, and radioligands for the P2Y(1) receptor SO COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING LA English DT Article DE adenosine-3 ',5 '-bisphosphate; MRS2179; MRS2279; MRS2500; P2Y receptors; P2Y(1) receptor; platelet aggregation; radioligand ID ADENINE-NUCLEOTIDE ANALOGS; BIOLOGICAL-ACTIVITY; ECTO-ATPASE; PLATELET-AGGREGATION; INTERNATIONAL UNION; POTENT ANTAGONISTS; ACYCLIC ANALOGS; P2Y1 RECEPTOR; IDENTIFICATION; DERIVATIVES AB The P2Y(1) receptor is a member of the P2Y family of nucleotide-activated G protein-coupled receptors, and it is an important therapeutic target based on its broad tissue distribution and essential role in platelet aggregation. We have designed a set of highly selective and diverse pharmacological tools for studying the P2Y(1) receptor using a rational approach to ligand design. Based on the discovery that bisphosphate analogues of the P2Y(1) receptor agonist, ADP, are partial agonists/competitive antagonists of this receptor, an iterative approach was used to develop competitive antagonists with enhanced affinity and selectivity. Halogen substitutions of the 2-position of the adenine ring provided increased affinity while an N-6 methyl substitution eliminated partial agonist activity. Furthermore, various replacements of the ribose ring with symmetrically branched, phosphorylated acyclic structures revealed that the ribose is not necessary for recognition at the P2Y(1) receptor. Finally, replacement of the ribose ring with a five member methanocarba ring constrained in the Northern conformation conferred dramatic increases in affinity to both P2Y(1) receptor antagonists as well as agonists. These combined structural modifications have resulted in a series of selective high affinity antagonists of the P2Y(1) receptor, two broadly applicable radioligands, and a high affinity agonist capable of selectively activating the P2Y(1) receptor in human platelets. Complementary receptor modeling and computational ligand docking have provided a putative structural framework for the drug-receptor interactions. A similar rational approach is being applied to develop selective ligands for other subtypes of P2Y receptors. C1 [Houston, Dayle; Harden, T. Kendall] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. [Costanzi, Stefano; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Harden, TK (reprint author), Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. EM tkh@med.unc.edu RI Jacobson, Kenneth/A-1530-2009; Costanzi, Stefano/G-8990-2013; OI Jacobson, Kenneth/0000-0001-8104-1493; Costanzi, Stefano/0000-0003-3183-7332 FU Howard Hughes Medical Institute; Intramural NIH HHS [Z01 DK031116-20]; NIGMS NIH HHS [GM38213, R01 GM038213] NR 55 TC 22 Z9 22 U1 0 U2 7 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1386-2073 J9 COMB CHEM HIGH T SCR JI Comb. Chem. High Throughput Screen PD JUL PY 2008 VL 11 IS 6 BP 410 EP 419 DI 10.2174/138620708784911474 PG 10 WC Biochemical Research Methods; Chemistry, Applied; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy GA 323OH UT WOS:000257455400001 PM 18673269 ER PT J AU Singh, SR Liu, W Hou, S AF Singh, S. Ram Liu, W. Hou, S. TI The adult Drosophila Malpighian tubules are maintained by multipotent stem cells SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Experimental-Biology CY JUL 06-10, 2008 CL Marseille, FRANCE SP Soc Expt Biol C1 [Singh, S. Ram; Liu, W.; Hou, S.] Natl Canc Inst Frederick, NIH, Frederick, MD USA. RI Singh, Shree Ram/B-7614-2008 OI Singh, Shree Ram/0000-0001-6545-583X NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1095-6433 J9 COMP BIOCHEM PHYS A JI Comp. Biochem. Physiol. A-Mol. Integr. Physiol. PD JUL PY 2008 VL 150 IS 3 SU S BP S133 EP S133 DI 10.1016/j.cbpa.2008.04.317 PG 1 WC Biochemistry & Molecular Biology; Physiology; Zoology SC Biochemistry & Molecular Biology; Physiology; Zoology GA 326AY UT WOS:000257631500299 ER PT J AU Tota, B Pellegrino, D Shiva, S Angelone, T Cerra, M Gladwin, M AF Tota, B. Pellegrino, D. Shiva, S. Angelone, T. Cerra, M. Gladwin, M. TI Nitrite modulation of cardiac contractility in vertebrate hearts SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Experimental-Biology CY JUL 06-10, 2008 CL Marseille, FRANCE SP Soc Expt Biol C1 [Tota, B.; Pellegrino, D.; Angelone, T.; Cerra, M.; Gladwin, M.] Univ Calabria, I-87030 Commenda Di Rende, Italy. [Shiva, S.] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1095-6433 J9 COMP BIOCHEM PHYS A JI Comp. Biochem. Physiol. A-Mol. Integr. Physiol. PD JUL PY 2008 VL 150 IS 3 SU S BP S125 EP S125 DI 10.1016/j.cbpa.2008.04.292 PG 1 WC Biochemistry & Molecular Biology; Physiology; Zoology SC Biochemistry & Molecular Biology; Physiology; Zoology GA 326AY UT WOS:000257631500276 ER PT J AU Wink, D AF Wink, D. TI Biochemistry of NO and RNOS in ischemia and reperfusion injury SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Experimental-Biology CY JUL 06-10, 2008 CL Marseille, FRANCE SP Soc Expt Biol C1 [Wink, D.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1095-6433 J9 COMP BIOCHEM PHYS A JI Comp. Biochem. Physiol. A-Mol. Integr. Physiol. PD JUL PY 2008 VL 150 IS 3 SU S BP S124 EP S124 DI 10.1016/j.cbpa.2008.04.288 PG 1 WC Biochemistry & Molecular Biology; Physiology; Zoology SC Biochemistry & Molecular Biology; Physiology; Zoology GA 326AY UT WOS:000257631500273 ER PT J AU Atkinson, NL Saperstein, SL Massett, HA Leonard, CR Grama, L Manrow, R AF Atkinson, Nancy L. Saperstein, Sandra L. Massett, Holly A. Leonard, Colleen Ryan Grama, Lakshmi Manrow, Rick TI Using the Internet to search for cancer clinical trials: A comparative audit of clinical trial search tools SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE online cancer services; cancer information; clinical trials; Internet; website ID PARTICIPATION; BARRIERS AB Advancing the clinical trial research process to improve cancer treatment necessitates helping people with cancer identify and enroll in. studies, and researchers are using the power of the Internet to facilitate this process. This study used a content analysis of online cancer clinical trial search tools to understand what people with cancer might encounter. The content analysis revealed that clinical trial search tools were easy to identify using a popular search engine, but their functionality and content varied greatly. Most required that users be fairly knowledgeable about their medical condition and sophisticated in their web navigation skills. The ability to search by a specific health condition or type of cancer was the most common search strategy. The more complex tools required that users input detailed information about their personal medical history and have knowledge of specific clinical trial terminology. Search tools, however, only occasionally advised users to consult their doctors regarding clinical trial decision-making. This, along with the complexity of the tools suggests that online search tools may not adequately facilitate the clinical trial recruitment process. Findings from this analysis can be used as a framework from which to systematically examine actual consumer experience with online clinical trial search tools. (c) 2008 Elsevier Inc. All rights reserved. C1 [Atkinson, Nancy L.; Saperstein, Sandra L.] Univ Maryland, Dept Publ & Community Hlth, College Pk, MD 20742 USA. [Grama, Lakshmi] NCI, Off Commun & Educ, Rockville, MD USA. [Manrow, Rick] NCI, Off Canc Informat Prod & Syst, Off Commun, Rockville, MD USA. RP Atkinson, NL (reprint author), Univ Maryland, Dept Publ & Community Hlth, Suite 2387,Valley Dr, College Pk, MD 20742 USA. EM atkinson@umd.edu FU None [Y1500007] NR 32 TC 14 Z9 14 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JUL PY 2008 VL 29 IS 4 BP 555 EP 564 DI 10.1016/j.cct.2008.01.007 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 317IY UT WOS:000257014600013 PM 18346942 ER PT J AU Smith, J Nichols, KK Baldwin, EK AF Smith, Janine Nichols, Kelly K. Baldwin, Edward K. TI Current patterns in the use of diagnostic tests in dry eye evaluation SO CORNEA LA English DT Article DE dry eye; dysfunctional tear syndrome; correlation; tests; symptoms ID PATIENT-REPORTED SYMPTOMS; OCULAR IRRITATION; DISEASE; SIGNS; RELIABILITY; ASSOCIATION; SEVERITY; VALIDITY; INDEX AB Purpose: To clarify the roles of objective signs and subjective symptoms in the diagnosis and management of dry eye by describing their use by a group of expert practitioners. Dry eye signs and symptoms do not always correlate well, and there is currently some controversy over the ideal roles of signs and symptoms and their actual use in clinical practice. Methods: A balanced panel of 16 participants in a scientific roundtable on dry eye reviewed 4 patient case studies and completed surveys ranking common diagnostic procedures assessing symptoms and signs by the order in which they would be used. Results: Symptom assessment was the predominant diagnostic method. The objective tests most commonly used during the initial examination were tear breakup time (93%), corneal staining (85%), tear film assessment (76%), conjunctival staining (74%), and the Schirmer test (54%). Most panelists used multiple tests, with a median of 6 tests used in the initial examination. Conclusions: Subjective symptoms and objective signs are both important in the diagnosis and management of dry eye, with the patient's symptoms and history playing a critical role. Most clinicians use objective signs in dry eye management. However, currently available diagnostic tests do not correlate reliably with symptom severity. Research aimed at developing accurate, objective, responsive measures of dry eye severity is needed. C1 [Nichols, Kelly K.] Ohio State Univ, Coll Optometry, Columbus, OH 43210 USA. [Baldwin, Edward K.] SynerMed Commun, Westborough, MA USA. [Smith, Janine] NEI, NIH, DHHS, Bethesda, MD 20892 USA. RP Smith, J (reprint author), NEI, NIH, DHHS, Bethesda, MD 20892 USA. NR 23 TC 42 Z9 47 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD JUL PY 2008 VL 27 IS 6 BP 656 EP 662 PG 7 WC Ophthalmology SC Ophthalmology GA 320HA UT WOS:000257223100008 PM 18580256 ER PT J AU Perkins, JG Cap, AP Weiss, BM Reid, TJ Bolan, CE AF Perkins, Jeremy G. Cap, Andrew P. Weiss, Brendan M. Reid, Thomas J. Bolan, Charles E. TI Massive transfusion and nonsurgical hemostatic agents SO CRITICAL CARE MEDICINE LA English DT Review DE massive transfusion; trauma; coagulopathy; hemostasis; blood components ID RECOMBINANT-FACTOR-VIIA; ACTIVATED FACTOR-VII; DISSEMINATED INTRAVASCULAR COAGULATION; FRESH-FROZEN PLASMA; RED-BLOOD-CELLS; V LIVER-INJURIES; ADJUNCTIVE HEMORRHAGE CONTROL; LIFE-THREATENING HEMORRHAGE; MULTIPLE ORGAN FAILURE; VITRO THROMBELASTOGRAPHY MEASUREMENTS AB Background. Hemorrhage in trauma is a significant challenge, accounting for 30% to 40% of all fatalities, second only to central nervous system injury as a cause of death. However, hemorrhagic death is the leading preventable cause of mortality in combat casualties and typically occurs within 6 to 24 hrs of injury. In cases of severe hemorrhage, massive transfusion may be required to replace more than the entire blood volume. Early prediction of massive transfusion requirements, using clinical and laboratory parameters, combined with aggressive management of hemorrhage by surgical and nonsurgical means, has significant potential to reduce early mortality. Discussion. Although the classification of massive transfusion varies, the most frequently used definition is ten or more units of blood in 24 hrs. Transfusion of red blood cells is intended to restore blood volume, tissue perfusion, and oxygen-carrying capacity; platelets, plasma, and cryoprecipitate are intended to facilitate hemostasis through prevention or treatment of coagulopathy. Massive transfusion is uncommon in civilian trauma, occurring in only 1% to 3% of trauma admissions. As a result of a higher proportion of penetrating injury in combat casualties, it has occurred in approximately 8% of Operation Iraqi Freedom admissions and in as many as 16% during the Vietnam conflict. Despite its potential to reduce early mortality, massive transfusion is not without risk. It requires extensive blood-banking resources and is associated with high mortality. Summary. This review describes the clinical problems associated with massive transfusion and surveys the nonsurgical management of hemorrhage, including transfusion of blood products, use of hemostatic bandages/agents, and treatment with hemostatic medications. C1 [Perkins, Jeremy G.; Cap, Andrew P.; Weiss, Brendan M.; Reid, Thomas J.] Walter Reed Army Med Ctr, Hematol Oncol Serv, Washington, DC 20307 USA. [Bolan, Charles E.] NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA. RP Perkins, JG (reprint author), Walter Reed Army Med Ctr, Hematol Oncol Serv, Washington, DC 20307 USA. EM jeremy.perkins1@us.army.mil NR 389 TC 50 Z9 55 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUL PY 2008 VL 36 IS 7 SU S BP S325 EP S339 DI 10.1097/CCM.0b013e31817e2ec5 PG 15 WC Critical Care Medicine SC General & Internal Medicine GA 324AU UT WOS:000257490700012 PM 18594260 ER PT J AU Glaser, RL Goldbach-Mansky, R AF Glaser, Rachel L. Goldbach-Mansky, Raphaela TI The spectrum of monogenic autoinflammatory syndromes: Understanding disease mechanisms and use of targeted therapies SO CURRENT ALLERGY AND ASTHMA REPORTS LA English DT Review ID FAMILIAL MEDITERRANEAN FEVER; RECURRENT MULTIFOCAL OSTEOMYELITIS; PEDIATRIC GRANULOMATOUS ARTHRITIS; MUCKLE-WELLS-SYNDROME; HYPER-IGD SYNDROME; NF-KAPPA-B; HYPERIMMUNOGLOBULINEMIA-D; CIAS1 MUTATIONS; PAPA SYNDROME; INFLAMMATORY ATTACKS AB Monogenic autoinflammatory diseases encompass a distinct and growing clinical entity of multisystem inflammatory diseases with known genetic defects in the innate immune system. The diseases present clinically with episodes of seemingly unprovoked inflammation (fever, rashes, and elevation of acute phase reactants). Understanding the genetics has led to discovery of new molecules involved in recognizing exogenous and endogenous danger signals, and the inflammatory response to these stimuli. These advances have furthered understanding of innate inflammatory pathways and spurred collaborative research in rheumatology and infectious diseases. The pivotal roles of interleukin (IL)1 beta in cryopyrin-associated periodic syndromes, tumor necrosis factor (TNF) in TNF receptor-associated periodic syndrome, and links to inflammatory cytokine dysregulation in other monogenic autoinflammatory diseases have resulted in effective therapies targeting proinflammatory cytokines IL-1 beta and TNF and uncovered other new potential targets for anti-inflammatory therapies. C1 [Glaser, Rachel L.; Goldbach-Mansky, Raphaela] NIAMSD, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Goldbach-Mansky, R (reprint author), NIAMSD, Natl Inst Hlth, Bldg 10,Room 6N-216A,10 Ctr Dr, Bethesda, MD 20892 USA. EM goldbacr@mail.nih.gov FU Intramural NIH HHS [NIH0013432915]; PHS HHS [NIH0013432915] NR 70 TC 31 Z9 31 U1 0 U2 1 PU CURRENT SCIENCE INC PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1529-7322 J9 CURR ALLERGY ASTHM R JI Curr. Allergy Asthma Rep. PD JUL PY 2008 VL 8 IS 4 BP 288 EP 298 DI 10.1007/s11882-008-0047-1 PG 11 WC Allergy; Immunology SC Allergy; Immunology GA 317WM UT WOS:000257051100003 PM 18606080 ER PT J AU Bedoya, VI Jaimes, FA Delgado, JC Rugeles, C Usuga, X Zapata, W Castano, ME Boasso, A Shearer, G Rugeles, MT AF Bedoya, Victoria Ines Jaimes, Fabian Alberto Delgado, Julio C. Rugeles, Claudia Usuga, Xiomara Zapata, Wildeman Castano, Maria Eugenia Boasso, Adriano Shearer, Gene Rugeles, Maria Teresa TI Fetal-maternal HLA-A and -B discordance is associated with placental RNase expression and anti-HIV-1 activity SO CURRENT HIV RESEARCH LA English DT Article DE anti-HIV-1 activity; RNases; HLA class-I discordance ID EOSINOPHIL-DERIVED NEUROTOXIN; IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN PANCREATIC RIBONUCLEASE; RESPIRATORY SYNCYTIAL VIRUS; TO-INFANT TRANSMISSION; DOUBLE-STRANDED-RNA; CATIONIC PROTEIN; HIV TYPE-1; ALLOANTIGEN RECOGNITION; ANTIVIRAL ACTIVITY AB The incidence of maternal-to-fetal human immunodeficiency virus type 1 (HIV-1) transmission is 25-30% in absence of antiretroviral therapy, and is inversely associated with Human leukocyte antigens (HLA) class-I discordance. Based on our earlier report that mixed lymphocyte reactions (MLR) induce a ribonuclease (RNase) that inhibits HIV-1 replication, we proposed that maternal-fetal alloantigen stimulation activates factors that protect the fetus against vertically-transmitted infections. We investigate here whether the degree of mother-infant HLA discordance associates with the ability to produce anti-HIV-1 alloantigen-stimulated factor (ASF), and affects placental RNases. We also determine whether such HLA association is influenced by the mother's HIV-1 status. Paired maternal and cord blood leukocytes were tested for the induction of ASF by MLR, and typed for HLA-A and -B. The placentas were tested for mRNA expression of three RNases. Neonate anti-mother, but not mother anti-neonate MLR generated supernatants with anti-HIV-1 activity, that was associated with HLA class I discordance. This HLA association was not seen in the HIV-infected cohort. HLA class I discordance was also associated with expression of placental RNase 1. Our findings are consistent with the hypothesis that HLA class I discordance induces expression of RNases in the placenta that contribute to innate host resistance to HIV-1 and other viral infections. C1 [Bedoya, Victoria Ines] Hosp Univ San Vicente de Paul, Tissue Bank, Medellin, Colombia. [Jaimes, Fabian Alberto] Univ Antioquia, Dept Internal Med, Acad Grp Clin Epidemiol, Medellin, Colombia. [Delgado, Julio C.] Univ Utah, Dept Pathol, Salt Lake City, UT USA. [Boasso, Adriano] Univ London Imperial Coll Sci Technol & Med, Chelsea & Westminster Hosp, Fac Med, Dept Immunol, London, England. [Shearer, Gene] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Bedoya, VI (reprint author), Hosp San Vicente de Paul, Calle 64,51 D 154, Medellin, Colombia. EM vibe@elhospital.org.co; mtrugel@udea.edu.co RI Jaimes, Fabian/R-4258-2016; OI Jaimes, Fabian/0000-0002-7315-5367; Boasso, Adriano/0000-0001-9673-6319 FU COLCIENCIAS, Bogota, Colombia [1115-04-12948]; ARUP Institute for Clinical and Experimental Pathology FX This research was supported by Grant 1115-04-12948 from COLCIENCIAS, Bogota, Colombia and ARUP Institute for Clinical and Experimental Pathology (to J.C.D.). The authors thank: Dr. Alvaro Hoyos and Dr. Lazaro Velez for patient recruitment; the physicians and nurses from Hospital Universitario San Vicente de Paul, Hospital General, Clinica el Prado and Hospital Marco Fidel Suarez for their participation and assistance in patient recruitment. NR 62 TC 4 Z9 4 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-162X J9 CURR HIV RES JI Curr. HIV Res. PD JUL PY 2008 VL 6 IS 4 BP 380 EP 387 DI 10.2174/157016208785132536 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 341WI UT WOS:000258745800012 PM 18691036 ER PT J AU Khanna, C AF Khanna, Chand TI Novel Targets With Potential Therapeutic Applications in Osteosarcoma SO CURRENT ONCOLOGY REPORTS LA English DT Article AB For patients with osteosarcoma, the development of metastases, often to the lungs, is the most common cause of death. Long-term outcomes for patients who present with localized or disseminated disease have largely remained unchanged over the past 20 years. Further improvements in outcome are not likely to come from intensification of cytotoxic chemotherapy; as such, new targets for treatment are needed. A view toward such targets in osteosarcoma may be constructed based on three common clinical features of the disease. These include the origin of osteosarcoma in the bone or primitive mesenchymal cells, the predictable process of metastatic progression characterized by this disease, and the development of metastatic lesions almost exclusively in the lung. It is likely and potentially favorable for some targets to be relevant for more than one process. This review summarizes novel targets under evaluation for the treatment of osteosarcoma based on these three features of the disease. C1 NCI, NIH, Pediat Oncol Branch, Tumor Metastasis Biol Sect, Bethesda, MD 20892 USA. RP Khanna, C (reprint author), NCI, NIH, Pediat Oncol Branch, Tumor Metastasis Biol Sect, 37 Convent Dr, Bethesda, MD 20892 USA. EM khannac@mail.nih.gov NR 70 TC 20 Z9 20 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3790 J9 CURR ONCOL REP JI Curr. Oncol. Rep. PD JUL PY 2008 VL 10 IS 4 BP 350 EP 358 DI 10.1007/s11912-008-0054-3 PG 9 WC Oncology SC Oncology GA V16AM UT WOS:000207842500013 PM 18778562 ER PT J AU Grotto, I Huerta, M Sharabi, Y AF Grotto, Itamar Huerta, Michael Sharabi, Yehonatan TI Hypertension and socioeconomic status SO CURRENT OPINION IN CARDIOLOGY LA English DT Review DE epidemiology; hypertension; prevention and control; socioeconomic status ID CARDIOVASCULAR RISK-FACTORS; AMBULATORY BLOOD-PRESSURE; JOB STRAIN; MULTILEVEL ANALYSIS; ADULTS; MEN; PREVALENCE; MORTALITY; IMPACT; WOMEN AB Purpose of review The impact of socioeconomic status on hypertension is complicated and unclear. In this article, we review the findings of recently published studies pertaining to the association between socioeconomic status and hypertension. Specifically, we focus on several potentially modifiable modes of pathogenesis involved in this association, including education, occupation, and social environment. We also review several mechanisms through which the effects of socioeconomic status on hypertension may be mediated. Recent findings Several modifiable socioeconomic determinants, such as education and occupation, are associated with hypertension, Additional socioeconomic status markers such as urban or rural dwelling and individual, local or national economic conditions are also associated with hypertension, although these associations are complicated and at times somewhat contradictory. Possible explanations for this impact include awareness of hypertension prevention and control and better accessibility and adherence to medical treatment among higher socioeconomic status groups, as well as low birth weight and higher job strain among lower socioeconomic status groups. Summary Low socioeconomic status is associated with higher blood pressure. There is a need to develop and test culturally appropriate interventions to reduce the prevalence of hypertension among these populations to minimize the resultant cardiovascular morbidity and mortality. C1 [Grotto, Itamar; Huerta, Michael] Ben Gurion Univ Negev, Fac Hlth Sci, Dept Epidemiol, IL-84105 Beer Sheva, Israel. [Grotto, Itamar] Israeli Minist Hlth, Publ Hlth Serv, Jerusalem, Israel. [Huerta, Michael] Chaim Sheba Med Ctr, Israel Def Forces Med Corps, IL-52621 Tel Hashomer, Israel. [Sharabi, Yehonatan] Tel Aviv Univ, Sackler Fac Med, Sheba Med Ctr, Hypertens Unit C, IL-69978 Tel Aviv, Israel. [Sharabi, Yehonatan] NINDS, Dept Clin Neurocardiol, NIH, Bethesda, MD 20892 USA. RP Grotto, I (reprint author), Ben Gurion Univ Negev, Fac Hlth Sci, Dept Epidemiol, POB 653, IL-84105 Beer Sheva, Israel. EM grotto@bgu.ac.il RI Grotto, Itamar/F-2028-2012 NR 22 TC 88 Z9 91 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-4705 J9 CURR OPIN CARDIOL JI Curr. Opin. Cardiol. PD JUL PY 2008 VL 23 IS 4 BP 335 EP 339 DI 10.1097/HCO.0b013e3283021c70 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 315HD UT WOS:000256868200008 PM 18520717 ER PT J AU Sokolic, R Kesserwan, C Candotti, F AF Sokolic, Robert Kesserwan, Chimene Candotti, Fabio TI Recent advances in gene therapy for severe congenital immunodeficiency diseases SO CURRENT OPINION IN HEMATOLOGY LA English DT Article DE clinical trials; gene therapy; insertion site analysis; insertional oncogenesis; primary immunodeficiency ID CHRONIC GRANULOMATOUS-DISEASE; ADENOSINE-DEAMINASE DEFICIENCY; LEUKOCYTE ADHESION DEFICIENCY; ZINC-FINGER NUCLEASES; T-CELL DEVELOPMENT; LENTIVIRAL VECTORS; HEMATOPOIETIC-CELLS; BONE-MARROW; INSERTIONAL MUTAGENESIS; METABOLIC DEFECTS AB Purpose of review To discuss new data on the safety and efficacy of the ongoing gene therapy trials for primary immune deficiencies, the first reports of new trials and the preclinical developments that are likely to be translated to the clinic in the near future. Recent findings Both clinical successes and severe adverse events continue to be reported in trials of gammaretroviral gene therapy for severe combined immune deficiency-X1, adenosine deaminase-deficient forms of severe combined immune deficiency and chronic granulomatous disease. Insertion site analyses of recently reported trials on all of these diseases have discovered preferential insertion in the 5' ends of genes, including potentially dangerous ones such as proto-oncogenes and signal transduction and proliferation genes. Preclinical work on rodent and canine models has tested novel vectors, including lentiviruses and foamy viruses. Summary Gene therapy for the most common forms of severe combined immune deficiency can lead to immune reconstitution in most patients, although a minority of patients has derived minimal clinical benefit and some have suffered severe adverse events including death. Ongoing preclinical work attempts to address the latter shortcoming. Meanwhile, in the presence of a careful risk-benefit assessment, gene therapy remains an appropriate subject of clinical investigation. C1 [Sokolic, Robert; Kesserwan, Chimene; Candotti, Fabio] NHGRI, Disorders Immun Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Sokolic, R (reprint author), NHGRI, Disorders Immun Sect, Genet & Mol Biol Branch, NIH, 49 Convent Dr,MSC 1611,Bldg 49,Room 3A04, Bethesda, MD 20892 USA. EM fabio@nhgri.nih.gov RI Sokolic, Robert/I-6072-2012 FU Intramural NIH HHS [Z01 HG000121-10, Z01 HG000122-10, Z99 HG999999] NR 67 TC 16 Z9 18 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1065-6251 EI 1531-7048 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD JUL PY 2008 VL 15 IS 4 BP 375 EP 380 DI 10.1097/MOH.0b013e328302c807 PG 6 WC Hematology SC Hematology GA 322MO UT WOS:000257379600015 PM 18536577 ER PT J AU Madsen-Bouterse, SA Xu, Y Petty, HR Romero, R AF Madsen-Bouterse, Sally A. Xu, Yi Petty, Howard R. Romero, Roberto TI Quantification of O-GlcNAc protein modification in neutrophils by flow cytometry SO CYTOMETRY PART A LA English DT Article DE neutrophil; O-GlcNAc; fMLF; PMA; intracellular protein; flow cytometry; immunofluorescence microscopy ID N-ACETYLGLUCOSAMINE; ACTIVATION AB Observations of intracellular O-linked beta-N-acetylglucosamine (O-GlcNAc) protein modification are primarily performed by Western blot or immunofluorescence microscopy. The goal of this study was to develop a flow cytometric-based assay for O-GlcNAc signaling and thus provide a more quantitative and rapid method to facilitate clinical analyses. Isolated peripheral blood neutrophils were stimulated with fMLF after adherence to glass cover slips. Cells in suspension were treated with either fMLF or PMA. Unstimulated cells served as controls. Neutrophils were fixed with formaldehyde and permeabilized with cold methanol before intracellular O-GlcNAc staining. Cells on cover slips were analyzed by fluorescence microscopy, and suspension cell data were acquired by flow cytometry. O-GlcNAc protein modification was increased following neutrophil stimulation with either 100 nM fMLF or 10 nM PMA. Increases were detected following either treatment using both flow cytometry and fluorescence microscopy. The time necessary for the completion of staining, data acquisition, and analysis was considerably less using flow cytometry. In addition, flow cytometry allows for the analysis of a substantially greater number of cells. Neutrophil protein modifications by O-GlcNAc are rapidly detected using flow cytometry and provide information similar to that observed using fluorescence microscopy. Published 2008 Wiley-Liss, Inc. C1 [Madsen-Bouterse, Sally A.; Xu, Yi; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD 20892 USA. [Petty, Howard R.] Univ Michigan, Sch Med, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA. [Romero, Roberto] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA. RP Romero, R (reprint author), NICHD, Perinatol Res Branch, NIH, DHHS, 3990 John R,4th Floor, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu FU Intramural NIH HHS [ZIA HD002401-17] NR 11 TC 1 Z9 1 U1 2 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD JUL PY 2008 VL 73A IS 7 BP 667 EP 672 DI 10.1002/cyto.a.20569 PG 6 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 319PL UT WOS:000257176000010 PM 18524014 ER PT J AU Ahmad, E Steinberg, SM Goldin, L Hess, CJ Caporaso, N Kreitman, RJ Wiestner, A Wilson, W White, T Marti, G Stetler-Stevenson, M AF Ahmad, Ejaz Steinberg, Seth M. Goldin, Lynn Hess, Christopher J. Caporaso, Neil Kreitman, Robert J. Wiestner, Adrian Wilson, Wyndham White, Therese Marti, Gerald Stetler-Stevenson, Maryalice TI Immunophenotypic features distinguishing familial chronic lymphocytic leukemia from sporadic chronic lymphocytic leukemia SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE familial chronic lymphocytic leukemia; sporadic chronic lymphocytic leukemia; immunophenotype; flow cytometry; survival; CD38 ID CD38 EXPRESSION; B-CLL; CLINICAL-COURSE; MUTATION STATUS; ANTICIPATION; PROFILES; NEOPLASMS; DIAGNOSIS; CELLS AB Background: Familial chronic lymphocytic leukemia (CLL) has the most frequent familial aggregation among hematological malignancies. Familial C LL families have been studied to identify susceptibility genes and other factors that contribute in the etiology of CLL. To date no study has been conducted to evaluate and compare patterns of cell surface antigen expression in familial CLL and sporadic CLL. Methods: The pattern of cell surface antigen expression was studied in familial and sporadic CLL to determine if unique identifiers of familial CLL could be detected. Survival in familial CLL verses sporadic CLL was compared and the association between prognosis and CD38 expression studied. Results: Familial and sporadic CLL demonstrated the same characteristic immunophenotype (positive for surface immunoglobulin, CD5, CD19, and CD23 with dim CD20, and CD22). CD2 and CD13 expression, however, were more frequent (30% of cases) in familial CLL (P = 0.0003 for CD2, P = 0.006 for CD13) than in sporadic CLL (2-6%). There was no significant difference in survival in the two groups studied. Although the incidence of CD38 expression was similar in familial and sporadic CLL (47% and 44% respectively) the association with prognosis differed. There was a trend to decreased survival in CD38 positive sporadic (P = 0.06) but not familial CLL patients. Conclusions: We conclude that detection of CD2 or CD13 expression in CLL suggests familial CLL and examination of family history for additional affected members is warranted. Furthermore, CD38 expression does not carry the negative prognosis observed in sporadic CLL. Published 2008 Wiley-Liss, Inc. C1 [Hess, Christopher J.; Stetler-Stevenson, Maryalice] NCI, Chief Flow Cytometry Unit, LP, CCR,NIH, Bethesda, MD 20892 USA. [Ahmad, Ejaz] Good Samaritan Hosp, Dayton, OH USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, CCR, NIH, Bethesda, MD 20892 USA. [Goldin, Lynn; Caporaso, Neil] NCI, Genet Epidemiol Branch, NIH, Bethesda, MD 20892 USA. [Kreitman, Robert J.] NCI, Mol Biol Lab, CCR, NIH, Bethesda, MD 20892 USA. [Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Wilson, Wyndham; White, Therese] NCI, Metab Branch, CCR, NIH, Bethesda, MD 20892 USA. [Marti, Gerald] US FDA, Ctr Biol & Res Evaluat, Off Cellular Tissues & Gene Therapies, Div Cell & Gene Therapies,Cellular & Tissue Branc, Bethesda, MD 20014 USA. RP Stetler-Stevenson, M (reprint author), NCI, Chief Flow Cytometry Unit, LP, CCR,NIH, Bldg 10,Room 2A33,Mail Stop 1500, Bethesda, MD 20892 USA. EM stetler@mail.nih.gov NR 29 TC 7 Z9 7 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD JUL PY 2008 VL 74B IS 4 BP 221 EP 226 DI 10.1002/cyto.b.20423 PG 6 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 315HX UT WOS:000256870500003 PM 18431797 ER PT J AU Ohtola, J Myers, J Akhtar-Zaidi, B Zuzindlak, D Sandesara, P Yeh, K Mackem, S Atit, R AF Ohtola, Jennifer Myers, John Akhtar-Zaidi, Batool Zuzindlak, Diana Sandesara, Pooja Yeh, Karen Mackem, Susan Atit, Radhika TI beta-Catenin has sequential roles in the survival and specification of ventral dermis SO DEVELOPMENT LA English DT Article DE dermis; cell fate; cell survival; skin; sternum ID HAIR FOLLICLE; CHICK-EMBRYOS; MOUSE; EXPRESSION; FATE; MESODERM; MICE; SKIN; DIFFERENTIATION; DERMOMYOTOME AB The dermis promotes the development and maintains the functional components of skin, such as hair follicles, sweat glands, nerves and blood vessels. The dermis is also crucial for wound healing and homeostasis of the skin. The dermis originates from the somites, the lateral plate mesoderm and the cranial neural crest. Despite the importance of the dermis in the structural and functional integrity of the skin, genetic analysis of dermal development in different parts of the embryo is incomplete. The signaling requirements for ventral dermal cell development have not been established in either the chick or the mammalian embryo. We have shown previously that Wnt signaling specifies the dorsal dermis from the somites. In this study, we demonstrate that Wnt/beta-catenin signaling is necessary for the survival of early ventral dermal progenitors. In addition, we show that, at later stages, Wnt/beta-catenin signaling is sufficient for ventral dermal cell specification. Consistent with the different origins of dorsal and ventral dermal cells, our results demonstrate both conserved and divergent roles of beta-catenin/Wnt signaling in dermal development. C1 [Ohtola, Jennifer; Myers, John; Akhtar-Zaidi, Batool; Zuzindlak, Diana; Sandesara, Pooja; Yeh, Karen; Atit, Radhika] Case Western Reserve Univ, Dept Biol, Cleveland, OH 44106 USA. [Mackem, Susan] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Atit, Radhika] Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. [Atit, Radhika] Case Western Reserve Univ, Dept Dermatol, Cleveland, OH 44106 USA. RP Atit, R (reprint author), Case Western Reserve Univ, Dept Biol, Cleveland, OH 44106 USA. EM rpa5@case.edu FU Intramural NIH HHS [Z01 SC009170-20]; NIDCR NIH HHS [R01 DE018470-02, R01 DE018470] NR 37 TC 32 Z9 32 U1 1 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JUL 1 PY 2008 VL 135 IS 13 BP 2321 EP 2329 DI 10.1242/dev.021170 PG 9 WC Developmental Biology SC Developmental Biology GA 310GD UT WOS:000256516000013 PM 18539925 ER PT J AU Kelley, MW AF Kelley, Matthew W. TI Leading Wnt down a PCP path: Cthrc1 acts as a coreceptor in the Wnt-PCP pathway SO DEVELOPMENTAL CELL LA English DT Editorial Material ID PLANAR CELL POLARITY AB Wnt signaling regulates many aspects of development through canonical and PCP signaling pathways. A paper by Yamamoto et al. in this issue of Developmental Cell identifies collagen triple helix repeat containing 1 as a Wnt-binding cofactor that specifically activates the Wnt-PCP pathway. C1 Natl Tech Inst Deafness & Other Commun Disorders, Sect Dev Neurosci, NIH, Bethesda, MD USA. RP Kelley, MW (reprint author), Natl Tech Inst Deafness & Other Commun Disorders, Sect Dev Neurosci, NIH, Bethesda, MD USA. EM kelleymt@nidcd.nih.gov NR 10 TC 5 Z9 6 U1 1 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD JUL PY 2008 VL 15 IS 1 BP 7 EP 8 DI 10.1016/j.devcel.2008.06.008 PG 2 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 325CU UT WOS:000257566600004 PM 18606135 ER PT J AU Belsky, J Booth-LaForce, C Bradley, R Brownell, CA Burchinal, M Campbell, SB Clarke-Stewart, KA Cox, M Friedman, SL Houts, R Kelly, JF Knoke, B Marshall, N McCartney, K Morgan-Lopez, A Morrison, F O'Brien, M Owen, MT Parke, R Payne, C Pianta, R Spieker, S Vandell, DL Weinraub, M AF Belsky, Jay Booth-LaForce, Cathryn Bradley, Robert Brownell, Celia A. Burchinal, Margaret Campbell, Susan B. Clarke-Stewart, K. Alison Cox, Martha Friedman, Sarah L. Houts, Renate Kelly, Jean F. Knoke, Bonnie Marshall, Nancy McCartney, Kathleen Morgan-Lopez, Antonio Morrison, Frederick O'Brien, Marion Owen, Margaret Tresch Parke, Ross Payne, Chris Pianta, Robert Spieker, Susan Vandell, Deborah Lowe Weinraub, Marsha CA Natl Inst Child Hlth TI Mothers' and fathers' support for child autonomy and early school achievement SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article DE mother-child relationships; father-child relationships; early academic achievement; child social adjustment; transition to school ID EFFORTFUL CONTROL; BEHAVIOR PROBLEMS; FAMILIES; KINDERGARTEN; CONSEQUENCES; PERFORMANCE; COMPETENCE; TRANSITION; ADJUSTMENT; MEDIATION AB Data were analyzed from 641 children and their families in the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development to test the hypotheses that in the early school years, mothers' and fathers' sensitive support for autonomy in observed parent-child interactions would each make unique predictions to children's reading and math achievement at Grade 3 (controlling for demographic variables), children's reading and math abilities at 54 months, and children's level of effortful control at 54 months and that these associations would be mediated by the level of and changes over time in children's observed self-reliance in the classroom from Grades I through 3. The authors found that mothers' and fathers' support for autonomy were significantly and uniquely associated with children's Grade 3 reading and math achievement with the above controls, but only for boys. For boys, the effect of mothers' support for child autonomy was mediated by higher self-reliance at Grade I and of fathers' support for child autonomy by greater increases in self-reliance from Grades 1 through 3. C1 [Belsky, Jay] Univ London, London WC1E 7HU, England. [Bradley, Robert; Kelly, Jean F.; Spieker, Susan] Univ Washington, Seattle, WA 98195 USA. [Bradley, Robert] Univ Arkansas, Little Rock, AR 72204 USA. [Brownell, Celia A.; Campbell, Susan B.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Burchinal, Margaret] Univ N Carolina, Chapel Hill, NC 27515 USA. [Clarke-Stewart, K. Alison] Univ Calif Irvine, Irvine, CA USA. [Houts, Renate; Knoke, Bonnie; Morgan-Lopez, Antonio] Res Triangle Inst, Res Triangle Pk, NC 27709 USA. [Marshall, Nancy] Wellesley Coll, Wellesley, MA 02181 USA. [Morgan-Lopez, Antonio] Harvard Univ, Cambridge, MA 02138 USA. [Morrison, Frederick] Univ Michigan, Ann Arbor, MI 48109 USA. [O'Brien, Marion; Payne, Chris] Univ N Carolina, Greensboro, NC USA. [Owen, Margaret Tresch] Univ Texas Dallas, Dallas, TX 75230 USA. [Parke, Ross] Univ Calif Riverside, Riverside, CA 92521 USA. [Pianta, Robert] Univ Virginia, Charlottesville, VA 22903 USA. [Vandell, Deborah Lowe] Univ Wisconsin, Madison, WI 53706 USA. [Weinraub, Marsha] Temple Univ, Philadelphia, PA 19122 USA. RP Cox, M (reprint author), Care of Martha J Cox, Univ N Carolina, NICHD, Early Child Care Res Network, 100 E Franklin St,CB 8115, Chapel Hill, NC 27599 USA. RI Marshall, Nancy/C-3428-2012 NR 84 TC 34 Z9 34 U1 6 U2 24 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD JUL PY 2008 VL 44 IS 4 BP 895 EP 907 DI 10.1037/0012-1649.44.4.895 PG 13 WC Psychology, Developmental SC Psychology GA 327NR UT WOS:000257736300001 ER PT J AU Berglund, ED Li, CY Poffenberger, G Ayala, JE Fueger, PT Willis, SE Jewell, MM Powers, AC Wasserman, DH AF Berglund, Eric D. Li, Candice Y. Poffenberger, Greg Ayala, Julio E. Fueger, Patrick T. Willis, Shannon E. Jewell, Marybeth M. Powers, Alvin C. Wasserman, David H. TI Glucose metabolism in vivo in four commonly used inbred mouse strains SO DIABETES LA English DT Article ID INSULIN SECRETORY FUNCTION; HIGH-FAT DIET; CONSCIOUS MOUSE; MICE; HOMEOSTASIS; RESISTANCE; DBA/2; SEVERITY; C57BL/6J; 129T2 AB OBJECTIVE-To characterize differences in whole-body glucose metabolism between commonly used inbred mouse strains. RESEARCH DESIGN AND METHODS-Hyperinsulinemic-euglycemic (similar to 8.5 mmol/l) and -hypoglycemic (similar to 3.0 mmol/l) clamps were done in catheterized, 5-h-fasted mice to assess insulin action and hypoglycemic counter-regulatory responsiveness. Hyperglycemic clamps (similar to 15 mmol/l) were done to assess insulin secretion and compared with results in perifused islets. RESULTS-Insulin action and hypoglycemic counter-regulatory and insulin secretory phenotypes varied considerably in four inbred mouse strains. In vivo insulin secretion was greatest in 129X1/Sv mice, but the counter-regulatory response to hypoglycemia was blunted. FVB/N mice in vivo showed no increase in glucose-stimulated insulin secretion, relative hepatic insulin resistance, and the highest counter-regulatory response to hypoglycemia. In DBA/2 mice, insulin action was lowest among the strains, and islets isolated had the greatest glucose-stimulated insulin secretion in vitro. In C57BL/6 mice, in vivo physiological responses to hyperinsulinemia at euglycemia, and hypoglycemia. were intermediate relative to other strains. Insulin secretion by C57BL/6 mice was similar to that in other strains in contrast to the blunted glucose-stimulated insulin secretion from isolated islets. CONCLUSIONS-Strain-dependent differences exist in four inbred mouse strains frequently used for genetic manipulation and study of glucose metabolism. These results are important for selecting inbred mice to study glucose metabolism and for interpreting and designing experiments. C1 [Berglund, Eric D.; Li, Candice Y.; Ayala, Julio E.; Powers, Alvin C.; Wasserman, David H.] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37212 USA. [Li, Candice Y.; Ayala, Julio E.; Wasserman, David H.] Vanderbilt Univ, NIH, Mouse Metab Phenotyping Ctr, Sch Med, Nashville, TN USA. [Poffenberger, Greg; Willis, Shannon E.; Jewell, Marybeth M.; Powers, Alvin C.] Vanderbilt Univ, Sch Med, Dept Med, Div Endocrinol Diabet & Metab, Nashville, TN 37212 USA. [Fueger, Patrick T.] Duke Univ, Med Ctr, Dept Pharmacol, Durham, NC 27710 USA. [Fueger, Patrick T.] Duke Univ, Med Ctr, Dept Canc Biol, Durham, NC USA. [Powers, Alvin C.] VA Tennessee Valley Healthcare Syst, Nashville, TN USA. RP Berglund, ED (reprint author), Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37212 USA. EM eric.d.berglund@vanderbilt.edu RI Fueger, Patrick/G-8956-2013 FU BLRD VA [I01 BX000666]; NIDDK NIH HHS [R56 DK054902, DK-20593, DK-50277, DK-54902, DK-59637, DK-63439, DK-66636, DK-68764, DK-69603, P30 DK020593, P60 DK020593, R01 DK050277, R01 DK054902, R01 DK068764, R01 DK069603, R21 DK063439, R21 DK066636, R33 DK066636, R37 DK050277, U01 DK089572, U24 DK059637] NR 30 TC 104 Z9 106 U1 0 U2 12 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2008 VL 57 IS 7 BP 1790 EP 1799 DI 10.2337/db07-1615 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 323BW UT WOS:000257420000007 PM 18398139 ER PT J AU Stolerman, ES Manning, AK McAteer, JB Dupuis, J Fox, CS Cupples, LA Meigs, JB Florez, JC AF Stolerman, Elliot S. Manning, Alisa K. McAteer, Jarred B. Dupuis, Josee Fox, Caroline S. Cupples, L. Adrienne Meigs, James B. Florez, Jose C. TI Haplotype structure of the ENPP1 gene and nominal association of the K121Q missense single nucleotide polymorphism with glycemic traits in the Framingham Heart Study SO DIABETES LA English DT Article ID GENOME-WIDE ASSOCIATION; MEMBRANE GLYCOPROTEIN PC-1; INSULIN-RESISTANCE; RISK LOCI; OBESITY; VARIANTS; RECEPTOR; GLUCOSE; SUSCEPTIBILITY; SENSITIVITY AB OBJECTTVE-A recent meta-analysis demonstrated a nominal association of the ectonucleotide pyrophosphatase phosphodiesterase I (ENPPI) K -> Q missense single nucleotide polymorphism (SNP) at position 121 with type 2 diabetes. We set out to confirm the association of ENPP1 K121Q with hyperglycemia, expand this association to insulin resistance traits, and determine whether the association stems from K121Q or another variant in linkage disequilibrium. with it. RESEARCH DESIGN AND METHODS-We characterized the haplotype structure of ENPPI and selected 39 tag SNPs that captured 96% of common variation in the region (minor allele frequency >= 50%) with an r2 value 0.80. We genotyped the SNPs in 2,511 Framingham Heart Study participants and used age- and sex-adjusted linear mixed effects (LME) models to test for association with quantitative metabolic traits. We also examined whether interaction between K121Q and BMI affected glycemic trait levels. RESULTS-The Q allele of K121Q (rs1044498) was associated with increased fasting plasma glucose (FPG), A1C, fasting insulin, and insulin resistance by homeostasis model assessment (HOMA-IR; all P = 0.01-0.006). Two noncoding SNPs (rs7775386 and rs7773477) demonstrated similar associations, but LME models indicated that their effects were not independent from K121Q. We found no association of K121Q with obesity, but interaction models suggested that the effect of the Q allele on FPG and HOMA-IR was stronger in those with a higher BMI (P = 0.008 and 0.01 for interaction, respectively). CONCLUSIONS-The Q allele of ENPP1 K121Q is associated with hyperglycemia and insulin resistance in whites. We found an adiposity-SNP interaction, with a stronger association of K121Q with diabetes-related quantitative traits in people with a higher BMI. C1 [Stolerman, Elliot S.; McAteer, Jarred B.; Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA. [Stolerman, Elliot S.; McAteer, Jarred B.; Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Diabet Unit, Boston, MA 02114 USA. [Stolerman, Elliot S.; McAteer, Jarred B.; Florez, Jose C.] Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02138 USA. [Stolerman, Elliot S.; McAteer, Jarred B.; Florez, Jose C.] MIT, Cambridge, MA 02139 USA. [Stolerman, Elliot S.; Meigs, James B.; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Manning, Alisa K.; Dupuis, Josee; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Florez, JC (reprint author), Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA. EM jcflorez@partners.org OI Cupples, L. Adrienne/0000-0003-0273-7965; Dupuis, Josee/0000-0003-2871-3603 FU NCRR NIH HHS [1S10-RR-163736-01A1]; NHLBI NIH HHS [N01-HC-25195, N01HC25195]; NIDDK NIH HHS [K23 DK065978, K23-DK-65978-04, K24 DK080140, K24 DK080140-01, K24-DK-080140]; NIGMS NIH HHS [T32 GM007748] NR 33 TC 31 Z9 31 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2008 VL 57 IS 7 BP 1971 EP 1977 DI 10.2337/db08-0266 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 323BW UT WOS:000257420000027 PM 18426862 ER PT J AU Mehta, SN Volkening, LK Anderson, BJ Nansel, T Weissberg-Benchell, J Wysocki, T Laffel, LMB AF Mehta, Sanjeev N. Volkening, Lisa K. Anderson, Barbara J. Nansel, Tonja Weissberg-Benchell, Jill Wysocki, Tim Laffel, Lori M. B. CA Family Management Childhood Diabet TI Dietary behaviors predict glycemic control in youth with type 1 diabetes SO DIABETES CARE LA English DT Article ID BLOOD-GLUCOSE CONTROL; ADOLESCENTS; CHILDREN AB OBJECTIVE - To investigate the association between dietary adherence and glycemic control among youth with type 1 diabetes. RESEARCH DESIGN AND METHODS - We conducted a cross-sectional analysis of 119 youth aged 9 -14 years (mean +/- SD 12.1 +/- 1.6 years) with diabetes duration >= 1 year (5.4 +/- 3.1 years). Dietary adherence was assessed using the Diabetes Self-Management Profile diet domain. Higher score defined greater dietary adherence. Glycemic control was determined by A1C. RESULTS - Dietary adherence score was inversely correlated with A1C (r = - 0.36, P < 0.0001). In a multivariate model (R-2 = 0.34, P < 0.0001), dietary adherence (P = 0.004), pump use (P = 0.03), and caregiver education (P = 0.01) were associated with A1C. A1C of youth in the lowest (9.0%) tertile of diet score was higher than A1C of youth in the middle (8.1%, P = 0.004) and upper (8.4%, P = 0.06) tertiles. Dietary adherence uniquely explained 8% of the variance in A1C in the model. CONCLUSIONS - Greater dietary adherence was associated with lower A1C among youth with type 1 diabetes. C1 [Mehta, Sanjeev N.; Volkening, Lisa K.; Laffel, Lori M. B.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Anderson, Barbara J.] Texas Childrens Hosp, Sect Endocrinol & Metab, Houston, TX 77030 USA. [Nansel, Tonja] NICHHD, Prevent Res Branch, Bethesda, MD 20892 USA. [Weissberg-Benchell, Jill] Childrens Mem Hosp, Dept Child & Adolescent Psychiat, Chicago, IL 60614 USA. [Wysocki, Tim] Nemours Childrens Clin, Div Psychol & Psychiat, Jacksonville, FL USA. RP Laffel, LMB (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. EM lori.laffel@joslin.harvard.edu OI Nansel, Tonja/0000-0002-8298-7595 FU NICHD NIH HHS [N01 HD003364] NR 9 TC 19 Z9 20 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 2008 VL 31 IS 7 BP 1318 EP 1320 DI 10.2337/dc07-2435 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 323CG UT WOS:000257421000008 PM 18390798 ER PT J AU Fox, CS Muntner, P AF Fox, Caroline S. Muntner, Paul TI Trends in diabetes, high cholesterol, and hypertension in chronic kidney disease among US adults: 1988-1994 to 1999-2004 SO DIABETES CARE LA English DT Article ID GLOMERULAR-FILTRATION-RATE; STAGE RENAL-DISEASE; RISK-FACTORS; UNITED-STATES; SERUM CREATININE; PREVALENCE; MELLITUS; MEN; MICROALBUMINURIA; DYSFUNCTION AB OBJECTIVE - The prevalence of chronic kidney disease (CKD) increased among U.S. adults from 1988-1994 to 1999-2004. We sought to explore the importance of trends in risk factors for CKD over time. RESEARCH DESIGN AND METHODS - The prevalence of cigarette smoking, obesity, hypertension, high cholesterol, and diabetes among U.S. adults with stage 3 CKD (estimated glomerular filtration rate <60 ml/min per 1.73 m(2)) and albuminuria (urinary albumin-to-creatinine ratio >= 30 mg/g), separately, were determined for 1988-1994 and 1999-2004 using data from serial National Health and Nutrition Examination Surveys. The prevalence ratios (PRs) for stage 3 CKD and albuminuria by the presence of these risk factors were compared across survey periods. RESULTS - The PR for CKD declined between 1988-1994 and 1999-2004 for obesity (PR 1.51 and 1.14 for 1988-1994 and 1999-2004, respectively; P for change = 0.010), hypertension (PR 2.60 and 1.70; P for change = 0.005), and high cholesterol (PR 1.58 and 1.20; P for change = 0.028). However, for diagnosed diabetes, the PR remained unchanged (1.64 and 1.62 P for change = 0.898). Similar results were observed for undiagnosed diabetes (PR of CKD 1.38 and 1.50; P for change = 0.373). The association of cigarette smoking was similar in each time period. Besides obesity, for which the association remained stable over time, similar patterns were observed for the PR of albuminuria. CONCLUSIONS - in terms of CKD, improvements in hypertension and high cholesterol management have been offset by both diagnosed and Undiagnosed diabetes. Further increases in CKD may occur if diabetes continues to increase. C1 [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Dept Med, Div Endocrinol Metab & Diabet, Boston, MA 02115 USA. [Muntner, Paul] Mt Sinai Sch Med, New York, NY USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA. EM foxca@nhlbi.nih.gov NR 31 TC 22 Z9 24 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 2008 VL 31 IS 7 BP 1337 EP 1342 DI 10.2337/dc07-2348 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 323CG UT WOS:000257421000013 PM 18436617 ER PT J AU Molenaar, EA Hwang, SJ Vasan, RS Grobbee, DE Meigs, JB D'Agostino, RB Levy, D Fox, CS AF Molenaar, Esther A. Hwang, Shih-Jen Vasan, Ramachandran S. Grobbee, Diederick E. Meigs, James B. D'Agostino, Ralph B. Levy, Daniel Fox, Caroline S. TI Burden and rates of treatment and control of cardiovascular disease risk factors in obesity - The Framingham Heart Study SO DIABETES CARE LA English DT Article ID BLOOD-PRESSURE; UNITED-STATES; PREVALENCE; TRIAL; HYPERTENSION; POPULATION; PREVENTION; OUTCOMES; GLUCOSE; TRENDS AB OBJECTIVE - Obesity is associated with an increased risk for cardiovascular disease (CVD). We sought to determine rates of treatment and control of CVD risk factors among normal weight, over-weight, and obese individuals in a community-based cohort. RESEARCH DESIGN AND METHODS - Participants free of CVD (n = 6,801; mean age 49 years; 54% women) from the Framingham Offspring and Third Generation cohorts who attended the seventh Offspring examination (1998-2001) or first Third Generation (2002-2005) examination were studied. RESULTS - Obese participants with hypertension were more likely to receive antihypertensive treatment (62.3%) than normal weight (58.7%) or overweight (59.0%) individuals (P = 0.002), but no differences in hypertension control across BMI subgroups among participants with hypertension were observed (36.7% [normal weight], 37.3% [overweight], and 39.4% [obese]; P = 0.48). Rates of lipid-lowering treatment were higher among obese participants with elevated LDL cholesterol (39.5%) compared with normal weight (34.2%) or overweight (36.4%) participants (P = 0.02), but control rates among those with elevated LDL cholesterol did not differ across BMI categories (26.7% [normal weight], 26.0% [overweight], and 29.2% [obese]; P = 0.11). There were no differences in diabetes treatment among participants with diabetes across BMI groups (69.2% [normal weight], 50.0% [overweight], 55.0% [obese]; P = 0.54), but obese participants with diabetes were less likely to have fasting blood glucose <126 mg/dl (15.7%) compared with normal weight (30.4%) or overweight (20.7%) participants (P = 0.02). CONCLUSIONS - These findings emphasize the suboptimal rates of treatment and control of CVD risk factors among overweight and obese individuals. C1 [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Molenaar, Esther A.; Grobbee, Diederick E.] Univ Utrecht, Med Ctr, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [Molenaar, Esther A.] Municipal Hlth Serv Utrecht, Utrecht, Netherlands. [Hwang, Shih-Jen; Levy, Daniel] NHLBI, Framingham Heart Study, Framingham, MA USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Cardiol & Prevent Med, Boston, MA 02118 USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Meigs, James B.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [D'Agostino, Ralph B.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. RP Fox, CS (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. EM foxca@nhlbi.nih.gov RI Grobbee, Diederick/C-7651-2014; OI Grobbee, Diederick/0000-0003-4472-4468; Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [2K24 HL 04334, K24 HL004334, N01-HC-25195, N01HC25195]; NIDDK NIH HHS [K24 DK080140, K24 DK080140-01] NR 22 TC 33 Z9 36 U1 0 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 2008 VL 31 IS 7 BP 1367 EP 1372 DI 10.2337/dc07-2413 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 323CG UT WOS:000257421000018 PM 18375414 ER PT J AU Brown, RJ Sinah, N Rother, KI AF Brown, Rebecca J. Sinah, Ninet Rother, Kristina I. TI Too much glucagon, too little insulin - Time course of pancreatic islet dysfunction in new-onset type 1 diabetes SO DIABETES CARE LA English DT Article ID POSTPRANDIAL HYPERGLYCEMIA; SECRETION; GLUCOSE; MELLITUS; CHILDREN AB OBJECTIVE - To determine the time course of changes in glucagon and insulin secretion in children with recently diagnosed type 1 diabetes. RESEARCH DESIGN AND METHODS - Glucagon and C-peptide concentrations were determined in response to standard mixed meals in 23 patients with type 1 diabetes aged 9.4 +/- 4.6 years, beginning within 6 weeks of diagnosis, and every 3 months thereafter for I year. RESULTS - Glucagon secretion in response to a physiologic stimulus (mixed meal) increased by 37% over 12 months, while C-peptide secretion declined by 45%. Fasting glucagon concentrations remained within the normal (nondiabetic) reference range. CONCLUSIONS - Postprandial hyperglucagonemia worsens significantly during the first year after diagnosis of type 1 diabetes and may represent a distinct therapeutic target. Fasting glucagon values may underestimate the severity of hyperglucagonemia. The opposing directions of abnormal glucagon and C-peptide secretion over time support the link between dysregulated glucagon secretion and declining P-cell function. C1 [Brown, Rebecca J.; Rother, Kristina I.] NIDDK, Bethesda, MD 20892 USA. [Sinah, Ninet] NIH, Ctr Clin, Bethesda, MD USA. RP Brown, RJ (reprint author), NIDDK, Bethesda, MD 20892 USA. EM brownrebecca@mail.nih.gov FU Intramural NIH HHS NR 8 TC 37 Z9 38 U1 1 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 2008 VL 31 IS 7 BP 1403 EP 1404 DI 10.2337/dc08-0575 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 323CG UT WOS:000257421000026 PM 18594062 ER PT J AU Tesauro, M Schinzari, F Rovella, V Melina, D Mores, N Barini, A Mettimano, M Lauro, D Iantorno, M Quon, MJ Cardillo, C AF Tesauro, Manfredi Schinzari, Francesca Rovella, Valentina Melina, Domenico Mores, Nadia Barini, Angela Mettimano, Marco Lauro, Davide Iantorno, Micaela Quon, Michael J. Cardillo, Carmine TI Tumor necrosis factor-alpha antagonism improves vasodilation during hyperinsulinemia in metabolic syndrome SO DIABETES CARE LA English DT Article ID VASCULAR SMOOTH-MUSCLE; INSULIN-RESISTANCE; TNF-ALPHA; EXPRESSION; CELLS AB OBJECTIVE - Obesity is associated with chronic inflammation due to overproduction of proinflammatory cytokines, including tumor necrosis factor (TNF)-alpha. We assessed the effects of TNF-alpha neutralization by infliximab on vascular reactivity during hyperinsulinemia in obesity-related metabolic syndrome. RESEARCH DESIGN AND METHODS - Vascular responses to intra-arterial infusion of acetylcholine (ACh) and sodium nitroprusside (SNP) were assessed in patients with metabolic syndrome, before and after administration of infliximab. RESULTS - Patients had blunted vasodilator responses to ACh and SNP during hyperinsulinemia compared with control subjects; a potentiation of the responsiveness to both ACh and SNP, however, was observed in patients following infliximab. The antioxidant vitamin C improved the vasodilator response to ACh in patients with metabolic syndrome, but its effect was not further enhanced by concurrent administration of infliximab. CONCLUSIONS - TNF-a neutralization ameliorates vascular reactivity in metabolic syndrome during hyperinsulinemia, likely in relation to decreased oxidative stress, thereby suggesting an involvement of inflammatory cytokines in vascular dysfunction of these patients. C1 [Tesauro, Manfredi; Rovella, Valentina; Lauro, Davide] Univ Roma Tor Vergata, Rome, Italy. [Schinzari, Francesca; Melina, Domenico; Mores, Nadia; Barini, Angela; Mettimano, Marco; Cardillo, Carmine] Univ Cattolica Sacro Cuore, Rome, Italy. [Iantorno, Micaela; Quon, Michael J.] Natl Ctr Complementary & Alternat Med, NIH, Bethesda, MD USA. RP Cardillo, C (reprint author), Univ Roma Tor Vergata, Rome, Italy. EM carmine.cardillo@rm.unicatt.it OI Quon, Michael/0000-0002-9601-9915; MORES, Nadia/0000-0002-4197-0914; Lauro, Davide/0000-0002-8597-4415 NR 10 TC 17 Z9 19 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 2008 VL 31 IS 7 BP 1439 EP 1441 DI 10.2337/dc08-0219 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 323CG UT WOS:000257421000033 PM 18390795 ER PT J AU de Souza-Pinto, NC Wilson, DM Stevsner, TV Bohr, VA AF de Souza-Pinto, Nadja C. Wilson, Dauid M., III Stevsner, Tinna V. Bohr, Vilhelm A. TI Mitochondrial DNA, base excision repair and neurodegeneration SO DNA REPAIR LA English DT Review DE BER; oxidative damage; mitochondrial DNA; 8-oxoG; DNA glycosylase ID SUBSTANTIA-NIGRA NEURONS; OXIDATIVELY DAMAGED DNA; DIFFERENTIAL INTRACELLULAR-LOCALIZATION; MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE BRAIN; MUTY HOMOLOG HMYH; SYNDROME GROUP-B; PARKINSONS-DISEASE; POLYMERASE-GAMMA; POINT MUTATIONS AB Neurodegeneration is a growing public health concern because of the rapid increase in median and maximum life expectancy in the developed world. Mitochondrial dysfunction seems to play a critical role in neurodegeneration, likely owing to the high energy demand of the central nervous system and its sole reliance on oxidative metabolism for energy production. Loss of mitochondrial function has been clearly demonstrated in several neuropathologies, most notably those associated with age, like Alzheimer's, Parkinson's and Huntington's diseases. Among the common features observed in such conditions is the accumulation of oxidative DNA damage, in particular in the mitochondrial DNA, suggesting that mitochondrial DNA instability may play a causative role in the development of these diseases. In this review we examine the evidence for the accumulation of oxidative DNA damage in mitochondria, and its relationship with loss of mitochondrial function and cell death in neural tissues. Oxidative DNA damage is repaired mainly by the base excision repair pathway. Thus, we review the molecular events and enzymes involved in base excision repair in mitochondria, and explore the possible role of alterations in mitochondrial base excision repair activities in premature aging and age-associated neurodegenerative diseases. Published by Elsevier B.V. C1 [de Souza-Pinto, Nadja C.; Wilson, Dauid M., III; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. [Stevsner, Tinna V.] Aarhus Univ, Danish Ctr Mol Gerontol, Dept Mol Biol, DK-8000 Aarhus C, Denmark. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM vbohr@mail.nih.gov RI Souza-Pinto, Nadja/C-3462-2013 OI Souza-Pinto, Nadja/0000-0003-4206-964X FU Intramural NIH HHS [Z01 AG000733-12] NR 144 TC 48 Z9 48 U1 1 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD JUL 1 PY 2008 VL 7 IS 7 BP 1098 EP 1109 DI 10.1016/j.dnarep.2008.03.011 PG 12 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 326KC UT WOS:000257656500009 PM 18485834 ER PT J AU Yang, JL Weissman, L Bohr, VA Mattson, MP AF Yang, Jenq-Lin Weissman, Lior Bohr, Vilhelm A. Mattson, Mark P. TI Mitochondrial DNA damage and repair in neurodegenerative disorders SO DNA REPAIR LA English DT Review DE Alzheimer's disease; apoptosis; base excision repair; Parkinson's disease; superoxide anion radical; uracil DNA glycosylase ID AMYOTROPHIC-LATERAL-SCLEROSIS; INCREASED OXIDATIVE DAMAGE; TRANSGENIC MOUSE MODEL; MILD COGNITIVE IMPAIRMENT; SUBSTANTIA-NIGRA NEURONS; BASE-EXCISION-REPAIR; AMYLOID-BETA-PEPTIDE; SPINAL MOTOR-NEURONS; ADULT-RAT BRAIN; ALZHEIMERS-DISEASE AB By producing ATP and regulating intracellular calcium levels, mitochondria are vital for the function and survival of neurons. Oxidative stress and damage to mitochondrial DNA during the aging process can impair mitochondrial energy metabolism and ion homeostasis in neurons, thereby rendering them vulnerable to degeneration. Mitochondrial abnormalities have been documented in all of the major neurodegenerative disorders-Alzheimer's, Parkinson's and Huntington's diseases, and amyotrophic lateral sclerosis. Mitochondrial DNA damage and dysfunction may be downstream of primary disease processes such as accumulation of pathogenic proteins. However, recent experimental evidence demonstrates that mitochondrial DNA damage responses play important roles in aging and in the pathogenesis of neurodegenerative diseases. Therapeutic interventions that target mitochondrial regulatory systems have been shown effective in cell culture and animal models, but their efficacy in humans remains to be established. Published by Elsevier B.V. C1 [Yang, Jenq-Lin; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Yang, Jenq-Lin; Weissman, Lior; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, Intramural Res Program, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012; OI Yang, Jenq-Lin/0000-0002-9897-8087 FU Intramural NIH HHS [Z01 AG000313-07] NR 139 TC 85 Z9 88 U1 2 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD JUL 1 PY 2008 VL 7 IS 7 BP 1110 EP 1120 DI 10.1016/j.dnarep.2008.03.012 PG 11 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 326KC UT WOS:000257656500010 PM 18463003 ER PT J AU Brooks, PJ AF Brooks, P. J. TI The 8,5 '-cyclopurine-2 '-deoxynucleosides: Candidate neurodegenerative DNA lesions in xeroderma pigmentosum, and unique probes of transcription and nucleotide excision repair SO DNA REPAIR LA English DT Review DE xeroderma pigmentosum; neurodegeneration; oxidative stress; reactive oxygen species; oxidative DNA damage; RNA polymerase ID CROSS-LINK LESIONS; RADICAL-INDUCED FORMATION; II I-COMPOUNDS; COCKAYNE-SYNDROME; HUMAN-CELLS; NEUROLOGICAL DISEASE; BASE DAMAGE; DIFFERENTIATED CELLS; SELECTIVE GENERATION; STRUCTURAL ORIGINS AB it is a commonly held view that oxidatively induced DNA lesions are repaired by the base excision repair (BER) pathway, whereas DNA lesions induced by UV light and other "bulky" chemical adducts are repaired by the nucleotide excision repair (NER) pathway. While this distinction is generally accurate, the 8,5'-cyclopurine deoxynucleosides represent an important exception, in that they are formed in DNA by the hydroxyl radical, but are specifically repaired by NER, not by BER. They are also strong blocks to nucleases and polymerases, including RNA polymerase II in human cells. In this review, I will discuss the evidence that these lesions are in part responsible for the neurodegeneration that occurs in some XP patients, and what additional evidence would be necessary to prove such a role. I will also consider other DNA lesions that might be involved in XP neurologic disease. Finally, I will also discuss how our recent studies of these lesions have generated novel insights into the process of transcriptional mutagenesis in human cells, as well as the value of studying these lesions not only for a better understanding of NER but also for other aspects of human health and disease. Published by Elsevier B.V. C1 NIAAA, Mol Neurobiol Sect, Neurogenet Lab, Bethesda, MD 20892 USA. RP Brooks, PJ (reprint author), NIAAA, Mol Neurobiol Sect, Neurogenet Lab, 5625 Fishers Lane,Room 3S-32, Bethesda, MD 20892 USA. EM pjbrooks@mail.nih.gov FU Intramural NIH HHS [Z01 AA000083-14, Z99 AA999999] NR 112 TC 68 Z9 70 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD JUL 1 PY 2008 VL 7 IS 7 BP 1168 EP 1179 DI 10.1016/j.dnarep.2008.03.016 PG 12 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 326KC UT WOS:000257656500014 PM 18495558 ER PT J AU Kakko, J Heilig, M Sarman, I AF Kakko, Johan Heilig, Markus Sarman, Ihsan TI Buprenorphine and methadone treatment of opiate dependence during pregnancy: Comparison of fetal growth and neonatal outcomes in two consecutive case series SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE pregnancy; heroin; maintenance treatment; methadone; buprenorphine; neonatal abstinence; fetal development ID HUMAN-IMMUNODEFICIENCY-VIRUS; ABSTINENCE SYNDROME; OPIOID DEPENDENCE; DOUBLE-BLIND; MANAGEMENT; WOMEN; INFANTS; DISORDERS; EXPOSURE; MOTHERS AB Aim: To compare the effects of fetal buprenorphine and methadone exposure during maintenance treatment of pregnant heroin dependent subjects. Design and setting: A population based comparison of consecutive, prospectively followed buprenorphine-exposed pregnancies in Stockholm County, Sweden, to retrospectively analyzed consecutive methadone-exposed pregnancies. Participants: All 47 pregnancies in 39 women with opiate dependence and buprenorphine maintenance treatment 2001-2006, and all 35 methadone-exposed pregnancies (26 women) 1982-2006 in Stockholm County. Measurements: Intrauterine growth, birth outcome, malformations, neonatal adaptation, withdrawal syndrome and infant mortality. Findings: Buprenorphine-exposed pregnancies resulted in 47 uneventful live births (2 twin pairs), 1 stillbirth (for which no explanation was found) and 1 miscarriage. The birth weight of the infants was normal. Neonatal abstinence syndrome (NAS) occurred in 19 cases (40.4%), the majority mild in nature and only 7 (14.9%) needing withdrawal treatment. Compared to 35 infants born after intrauterine methadone exposure at the same hospital since 1982 (77.8% of them exhibiting NAS and 52.8% needing withdrawal treatment), there were significant advantages with buprenorphine treatment: birth weight was higher, due to longer gestation. Incidence of NAS of any intensity, as well as incidence of NAS that required pharmacological treatment was lower, while length of hospital stay was shorter. When buprenorphine treatment started pre-conception, NAS at any level was significantly less frequent than in subjects with post-conception initiated treatment (7/27, 26%; 12/20, 60%, respectively). Conclusions: Data from this non-randomized comparison suggest that buprenorphine may offer advantages for treatment of opiate dependence during pregnancy. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Kakko, Johan; Heilig, Markus] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. [Heilig, Markus] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. [Sarman, Ihsan] So Hosp Stockholm, Dept Clin Sci, Stockholm, Sweden. RP Sarman, I (reprint author), Sachsska Childrens Hosp, Dept Paediat, Stockholm So Hosp, S-11883 Stockholm, Sweden. EM ihsan.sarman@sodersjukhuset.se OI Heilig, Markus/0000-0003-2706-2482 NR 31 TC 88 Z9 89 U1 0 U2 12 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JUL 1 PY 2008 VL 96 IS 1-2 BP 69 EP 78 DI 10.1016/j.drugalcdep.2008.01.025 PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 317JY UT WOS:000257017300008 PM 18355989 ER PT J AU Blanco, C Ogburn, E de los Cobos, JP Lujan, J Nunes, EV Grant, B Liu, SM Hasin, DS AF Blanco, Carlos Ogburn, Elizabeth de los Cobos, Jose Perez Lujan, Juan Nunes, Edward V. Grant, Bridget Liu, Shang-Min Hasin, Deborah S. TI DSM-IV criteria-based clinical subtypes of cannabis use disorders: Results from the National Epidemiological Survey on Alcohol and Related Conditions (NESARC) SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE cannabis use disorder; subtypes; epidemiological survey; DSM-IV criteria ID INTERVIEW SCHEDULE AUDADIS; GENERAL-POPULATION SAMPLE; YOUTH TREATMENT CYT; UNITED-STATES; MARIJUANA USE; DRUG-DEPENDENCE; ABUSE; RELIABILITY; DISABILITIES; COOCCURRENCE AB Prior research documented high homogeneity of alcohol use disorders (AUDs) as clinical entities. However, it is unknown whether this finding extends to other substance use disorders. We investigated this by examining the prevalence of all possible DSM-IV criteria-based clinical subtypes of current and lifetime cannabis use disorders in the general population. The number of possible (i.e., theoretical) clinical subtypes of cannabis abuse and dependence based on different combinations of the DSM-IV criteria was calculated using the combinatorial function. This number was compared with the subtypes actually observed in the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a large U.S. national sample (N = 43,093). Clinical and demographic correlates of the subtypes were examined with chi(2) tests whose target population was the United States civilian non-institutionalized population. All DSM-IV cannabis abuse and dependence criteria were assessed with the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version (AUDADIS-IV). Of all possible cannabis dependence subtypes, 29 (69%) were observed in the 12-month timeframe, and 41 (98%) in the lifetime timeframe. The corresponding numbers of subtypes for cannabis abuse were 12 (75%), current and 15 (100%), lifetime. These findings suggest that, in contrast to alcohol disorders, cannabis use disorders were highly heterogeneous. Future research should investigate whether there are differences in the course and treatment response of these clinical subtypes of cannabis use disorders, and the heterogeneity of other substance use disorders. (C) 2008 Published by Elsevier Ireland Ltd. C1 [Grant, Bridget] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA. [Blanco, Carlos; Ogburn, Elizabeth; Lujan, Juan; Nunes, Edward V.; Liu, Shang-Min; Hasin, Deborah S.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Blanco, Carlos; Ogburn, Elizabeth; Lujan, Juan; Nunes, Edward V.; Liu, Shang-Min; Hasin, Deborah S.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY 10032 USA. [Blanco, Carlos; Ogburn, Elizabeth; Lujan, Juan; Nunes, Edward V.; Liu, Shang-Min; Hasin, Deborah S.] Columbia Univ, Dept Psychiat, Coll Phys & Surg, New York, NY 10032 USA. [de los Cobos, Jose Perez] Hosp Santa Creu & Sant Pau, Addict Behav Unit, Dept Psychiat, Barcelona 08025, Spain. RP Grant, B (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Room 3077,MS 9304,5635 Fishers Lane, Bethesda, MD 20892 USA. EM bgrant@willco.niaaa.nih.gov RI Blanco, Carlos/I-4906-2013; Perez de los Cobos, Jose/Q-2734-2016 OI Blanco, Carlos/0000-0001-6187-3057; Perez de los Cobos, Jose/0000-0002-9796-5823 FU NIAAA NIH HHS [K05 AA014223, K05 AA 014223]; NIDA NIH HHS [K23 DA000482, K23 DA00482, R01 DA019606, R01 DA020783] NR 40 TC 9 Z9 9 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JUL 1 PY 2008 VL 96 IS 1-2 BP 136 EP 144 DI 10.1016/j.drugalcdep.2008.02.008 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 317JY UT WOS:000257017300015 PM 18420357 ER PT J AU Memoli, MJ Morens, DM Taubenberger, JK AF Memoli, Matthew J. Morens, David M. Taubenberger, Jeffery K. TI Pandemic and seasonal influenza: therapeutic challenges SO DRUG DISCOVERY TODAY LA English DT Review ID VIRUSES ISOLATED WORLDWIDE; A H5N1 VIRUS; STAPHYLOCOCCUS-AUREUS; ADAMANTANE RESISTANCE; IN-VITRO; INFECTION; MORTALITY; TRANSMISSION; OSELTAMIVIR; MANAGEMENT AB Influenza A viruses cause significant morbidity and mortality annually, and the threat of a pandemic underscores the need for new therapeutic strategies. Here, we briefly discuss novel antiviral agents under investigation, the limitations of current antiviral therapy and stress the importance of secondary bacterial infections in seasonal and pandemic influenza. Additionally, the lack of new antibiotics available to treat increasingly drug resistant organisms such as methicillin-resistant Staphylococcus aureus, pneumococci, Acinetobacter, extended spectrum beta-lactamase producing gram negative bacteria and Clostridium difficile is highlighted as an important component of influenza treatment and pandemic preparedness. Addressing these problems will require a multidisciplinary approach, which includes the development of novel antivirals and new antibiotics, as well as a better understanding of the role secondary infections play on the morbidity and mortality of influenza infection. C1 [Memoli, Matthew J.; Taubenberger, Jeffery K.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Memoli, MJ (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. EM memolim@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000995-01, Z99 AI999999] NR 71 TC 28 Z9 29 U1 2 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 EI 1878-5832 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD JUL PY 2008 VL 13 IS 13-14 BP 590 EP 595 DI 10.1016/j.drudis.2008.03.024 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 330YD UT WOS:000257977800006 PM 18598914 ER PT J AU Yamamoto, Y Negishi, M AF Yamamoto, Yukio Negishi, Masahiko TI The antiapoptotic factor growth arrest and DNA-damage-inducible 45 beta regulates the nuclear receptor constitutive active/androstane receptor-mediated transcription SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID RESPONSIVE ENHANCER MODULE; ANDROSTANE RECEPTOR; X-RECEPTOR; CYP2B GENE; CAR; MOUSE; ACTIVATION; EXPRESSION; INDUCTION; LIVER AB The nuclear receptor constitutive active/androstane receptor (CAR) up-regulated expression of the apoptotic growth arrest and DNA-damage-inducible 45 beta (GADD45B) gene in HepG2 cells. Overexpression of GADD45B augmented CAR-mediated induction of the human CYP2B gene by the CAR activator 1,4-bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP) and coactivated CAR-dependent transcription of the NR1-luciferase reporter gene. Small interfering RNA knockdown of GADD45B resulted in repression of both the induction and the coactivation. Induction of the mouse Cyp2b10 gene by TCPOBOP was profoundly attenuated in the primary hepatocytes prepared from GADD45B-knockout mice compared with those from wild-type mice. Because CAR is a key transcription factor that activates the genes that encode for xenobiotic metabolizing enzymes and transporters, GADD45B, acting as a CAR coactivator and coregulating CAR target genes, may be involved in hepatic drug metabolism and excretion of xenobiotics. C1 [Yamamoto, Yukio; Negishi, Masahiko] NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Negishi, M (reprint author), NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. EM negishi@niehs.nih.gov FU Intramural NIH HHS [Z01 ES080040-22] NR 30 TC 22 Z9 22 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD JUL PY 2008 VL 36 IS 7 BP 1189 EP 1193 DI 10.1124/dmd.108.020628 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 315UG UT WOS:000256905100001 PM 18362160 ER PT J AU Ciribilli, Y Andreotti, V Menendez, D Schoenfelder, G Resnick, MA Inga, A AF Ciribilli, Y. Andreotti, V. Menendez, D. Schoenfelder, G. Resnick, M. A. Inga, A. TI Understanding the complex crosstalk between p53 and the estrogen receptors at a polymorphic variant of the VEGF receptor FIt-1 promoter SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 20th Meeting of the European-Association-for-Cancer-Research CY JUL 05-08, 2008 CL Lyon, FRANCE SP European Assoc Canc Res C1 [Ciribilli, Y.; Andreotti, V.; Inga, A.] Ist Nazl Ric Canc, Mol Mutagenesis Unit, I-16132 Genoa, Italy. [Menendez, D.; Resnick, M. A.] NIEHS, Mol Genet Lab, Res Triangle Pk, NC USA. [Schoenfelder, G.] Univ Wurzburg, Inst Pharmacol & Toxicol, Wurzburg, Germany. NR 0 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 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD JUL PY 2008 VL 6 IS 9 BP 23 EP 23 DI 10.1016/S1359-6349(08)71265-5 PG 1 WC Oncology SC Oncology GA 330DF UT WOS:000257919000091 ER PT J AU Biong, M Brill, I Johansen, F Bremnes, Y Burdette, L Yaeger, M Ursin, G Gram, IT Kristensen, V AF Biong, M. Brill, I. Johansen, F. Bremnes, Y. Burdette, L. Yaeger, M. Ursin, G. Gram, I. T. Kristensen, V. TI Genotypes and haplotypes in the insulin-like growth factors their receptors and binding proteins in relation to plasma metabolic levels and mammographic density SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 20th Meeting of the European-Association-for-Cancer-Research CY JUL 05-08, 2008 CL Lyon, FRANCE SP European Assoc Canc Res C1 [Biong, M.; Johansen, F.; Kristensen, V.] Norwegian Radium Hosp, Dept Genet, Oslo, Norway. [Brill, I.] Univ Alabama, Dept Epidemiol, Birmingham, AL USA. [Bremnes, Y.; Gram, I. T.] Univ Tromso, Inst Community Med, Tromso, Norway. [Burdette, L.; Yaeger, M.] Natl Canc Inst, Core Genotyping Facil, Bathesda, MD USA. [Ursin, G.] Univ Oslo, Inst Nutr Res, Oslo, Norway. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD JUL PY 2008 VL 6 IS 9 BP 47 EP 47 DI 10.1016/S1359-6349(08)71354-5 PG 1 WC Oncology SC Oncology GA 330DF UT WOS:000257919000180 ER PT J AU Gonzalez-Moreno, O Lecanda, J Segura, V Serrano, D Catena, R Green, JE Calvo, A AF Gonzalez-Moreno, O. Lecanda, J. Segura, V. Serrano, D. Catena, R. Green, J. E. Calvo, A. TI Increased expression of VEGF in a prostate intraepithelial neoplasia (PIN)-like cell line leads to Epithelia1-to-Mesenchymal transition (EMT) SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 20th Meeting of the European-Association-for-Cancer-Research CY JUL 05-08, 2008 CL Lyon, FRANCE SP European Assoc Canc Res C1 [Gonzalez-Moreno, O.; Serrano, D.; Catena, R.; Calvo, A.] Ctr Appl Med Res, Div Oncol, Pamplona, Spain. [Lecanda, J.] Ctr Appl Med Res, Div Hepatol & Gene Therapy, Pamplona, Spain. [Segura, V.] Univ Navarra, CEIT & TECNUM, E-31080 Pamplona, Spain. [Green, J. E.] NIH, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. RI Segura, Victor/E-4531-2010 OI Segura, Victor/0000-0002-7740-6290 NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD JUL PY 2008 VL 6 IS 9 BP 50 EP 50 DI 10.1016/S1359-6349(08)71364-8 PG 1 WC Oncology SC Oncology GA 330DF UT WOS:000257919000190 ER PT J AU Thomas, G Hoover, R Hunter, D Chanock, S AF Thomas, G. Hoover, R. Hunter, D. Chanock, S. TI Genome wide association studies for breast and prostate cancer susceptibility loci in the CGEMS initiative SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 20th Meeting of the European-Association-for-Cancer-Research CY JUL 05-08, 2008 CL Lyon, FRANCE SP European Assoc Canc Res C1 [Thomas, G.; Hoover, R.; Chanock, S.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Hunter, D.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD JUL PY 2008 VL 6 IS 9 BP 64 EP 64 DI 10.1016/S1359-6349(08)71419-8 PG 1 WC Oncology SC Oncology GA 330DF UT WOS:000257919000244 ER PT J AU Weinberg, CR AF Weinberg, C. R. TI Issues and opportunities in family-based designs for young-onset cancers SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 20th Meeting of the European-Association-for-Cancer-Research CY JUL 05-08, 2008 CL Lyon, FRANCE SP European Assoc Canc Res C1 [Weinberg, C. R.] Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD JUL PY 2008 VL 6 IS 9 BP 64 EP 64 DI 10.1016/S1359-6349(08)71420-4 PG 1 WC Oncology SC Oncology GA 330DF UT WOS:000257919000245 ER PT J AU Nummela, P Yin, M Kielosto, M Leaner, V Birrer, MJ Holtta, E AF Nummela, P. Yin, M. Kielosto, M. Leaner, V. Birrer, M. J. Holtta, E. TI Up-regulation of thymosin beta A is a determinant of the transformed phenotype and invasiveness of mouse fibrosarcoma cells SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 20th Meeting of the European-Association-for-Cancer-Research CY JUL 05-08, 2008 CL Lyon, FRANCE SP European Assoc Canc Res C1 [Nummela, P.; Yin, M.; Kielosto, M.; Holtta, E.] Haartman Inst, Helsinki, Finland. [Nummela, P.; Yin, M.; Kielosto, M.; Holtta, E.] Univ Helsinki, Cent Hosp, Dept Pathol, Helsinki, Finland. [Leaner, V.; Birrer, M. J.] Ctr Canc Res Natl Canc Inst, Cell Canc Biol Dept, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD JUL PY 2008 VL 6 IS 9 BP 77 EP 78 DI 10.1016/S1359-6349(08)71473-3 PG 2 WC Oncology SC Oncology GA 330DF UT WOS:000257919000295 ER PT J AU Brock, K Gridley, G Chiu, BC Ershow, AG Lynch, CF Cantor, KP AF Brock, K. Gridley, G. Chiu, B. C. Ershow, A. G. Lynch, C. F. Cantor, K. P. TI Increased intake of fruits and vegetables high in vitamin C and fibre is associated with decreased risk of renal cell carcinoma in the US SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 20th Meeting of the European-Association-for-Cancer-Research CY JUL 05-08, 2008 CL Lyon, FRANCE SP European Assoc Canc Res C1 [Brock, K.] Univ Sydney, Fac Hlth Sci, Sydney, NSW 2006, Australia. [Gridley, G.; Cantor, K. P.] DCEG Natl Canc Inst, NIH DHHS, Bethesda, MD USA. [Chiu, B. C.] N Western Univ, Evanston, IL USA. [Ershow, A. G.] NHLBI, NIH DHHS, Bethesda, MD 20892 USA. [Lynch, C. F.] Univ Iowa, Dept Epidemiol, Coll Publ Hlth, Iowa City, IA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD JUL PY 2008 VL 6 IS 9 BP 103 EP 103 DI 10.1016/S1359-6349(08)71571-4 PG 1 WC Oncology SC Oncology GA 330DF UT WOS:000257919000393 ER PT J AU Heck, JE Berthiller, J Vaccarellal, S Winn, DM Smith, EM Shangina, O Schwartz, SM Purdue, M Eluf-Netol, J Menezes, A McClean, MD Matos, E Koifman, S Kelsey, KT Herrero, R Hayes, RB Franceschi, S Wunsch, V Fernandez, L Daudt, AW Curado, MP Chen, C Castelisague, X Ferro, G Brennan, P Boffetta, P Hashibe, M AF Heck, J. E. Berthiller, J. Vaccarellal, S. Winn, D. M. Smith, E. M. Shangina, O. Schwartz, S. M. Purdue, M. Eluf-Netol, J. Menezes, A. McClean, M. D. Matos, E. Koifman, S. Kelsey, K. T. Herrero, R. Hayes, R. B. Franceschi, S. Wuensch-Filho, V. Fernandez, L. Daudt, A. W. Curado, M. P. Chen, C. Castelisague, X. Ferro, G. Brennan, P. Boffetta, P. Hashibe, M. TI Sexual behaviors and the risk of head and neck cancers SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT International Conference on Integrative Molecular Cancer Epidemiology CY JUL 03-05, 2008 CL Lyon, FRANCE SP Int Acgy Res Canc, European Assoc Canc Res, Amer Assoc Canc Res, Network Excellence Canc, Nutr & Individual Susceptibil C1 [Winn, D. M.; Hayes, R. B.] NCI, Bethesda, MD 20892 USA. [Heck, J. E.; Berthiller, J.; Vaccarellal, S.; Franceschi, S.; Curado, M. P.; Ferro, G.; Brennan, P.; Boffetta, P.; Hashibe, M.] Int Agcy Res Canc, F-69372 Lyon, France. [Smith, E. M.] Univ Iowa, Coll Publ Hlth, Iowa City, IA USA. [Shangina, O.] Russian Acad Med Sci, Canc Res Ctr, Moscow, Russia. [Schwartz, S. M.; Chen, C.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Eluf-Netol, J.; Wuensch-Filho, V.] Univ Sao Paulo, Sao Paulo, Brazil. [Menezes, A.] Univ Fed Pelotas, Pelotas, Brazil. [McClean, M. D.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Matos, E.] Univ Buenos Aires, Inst Oncol Angel H Roffo, RA-1053 Buenos Aires, DF, Argentina. [Koifman, S.] Escola Nacl Suade Publ, Rio de Janeiro, Brazil. [Kelsey, K. T.] Brown Univ, Providence, RI 02912 USA. [Herrero, R.] Inst Invest Epidemiol, San Jose, Costa Rica. [Fernandez, L.; Castelisague, X.] Inst Oncol & Radiobiol, Havana, Cuba. [Daudt, A. W.] Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil. RI Wunsch Filho, Victor/C-4475-2012; Epidemiologicas, Centro de pesquisas /D-4561-2013; Menezes, Ana/G-7266-2012; Kelsey, Karl/I-1252-2014; McClean, Michael/J-2934-2015 NR 0 TC 0 Z9 0 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD JUL PY 2008 VL 6 IS 9 BP 193 EP 194 DI 10.1016/S1359-6349(08)71863-9 PG 2 WC Oncology SC Oncology GA 330DF UT WOS:000257919000683 ER PT J AU Etemadi, A Godschalk, R Islami, F van Schooten, FJ Pourshams, A Fazeltabar, A Boffeta, P Kamangar, F Beckers, L Malekzadeh, R AF Etemadi, A. Godschalk, R. Islami, F. van Schooten, F. J. Pourshams, A. Fazeltabar, A. Boffeta, P. Kamangar, F. Beckers, L. Malekzadeh, R. TI Polymorphisms in genes related to xenobiotic metabolism in a high-risk area for esophageal cancer in Northeast Iran SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 20th Meeting of the European-Association-for-Cancer-Research CY JUL 05-08, 2008 CL Lyon, FRANCE SP European Assoc Canc Res C1 [Etemadi, A.; Pourshams, A.; Fazeltabar, A.; Malekzadeh, R.] Univ Tehran Med Sci, Digest Dis Res Ctr, Tehran, Iran. [Etemadi, A.; Godschalk, R.; van Schooten, F. J.; Beckers, L.] Maastricht Univ, Dept Hlth Risk Anal & Toxicol, Maastricht, Netherlands. [Islami, F.; Boffeta, P.] Int Agcy Res Canc, F-69372 Lyon, France. [Kamangar, F.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD USA. RI Etemadi, Arash/C-1386-2016 OI Etemadi, Arash/0000-0002-3458-1072 NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD JUL PY 2008 VL 6 IS 9 BP 202 EP 202 DI 10.1016/S1359-6349(08)71894-9 PG 1 WC Oncology SC Oncology GA 330DF UT WOS:000257919000714 ER PT J AU Lee, HJ Caldwell, HK Macbeth, AH Tolu, SG Young, WS AF Lee, Heon-Jin Caldwell, Heather K. Macbeth, Abbe H. Tolu, Selen G. Young, W. Scott TI A conditional knockout mouse line of the oxytocin receptor SO ENDOCRINOLOGY LA English DT Article ID MATERNAL-BEHAVIOR; SOCIAL COGNITION; VASOPRESSIN 1A; MICE; GENE; HUMANS; RECOMBINATION; PARTURITION; EXPRESSION; DEFICITS AB Oxytocin plays important roles in reproductive physiology and various behaviors, including maternal behavior and social memory. Its receptor (Oxtr) is present in peripheral tissues and brain, so a conditional knockout (KO, -/-) would be useful to allow elimination of the receptor in specific sites at defined times. We created a line of mice in which loxP sites flank Oxtr coding sequence (floxed) enable Cre recombinase-mediated inactivation of the receptor. We expressed Cre recombinase in these mice either in all tissues (Oxtr(-/-)) or the forebrain (Oxtr(FB/FB)) using the Ca2+/calmodulin-dependent protein kinase II alpha promoter. The latter KO has reduced Oxtr binding beginning 21-28 d postnatally, leading to prominent reductions in the lateral septum, hippocampus, and ventral pallidum. The medial amygdala is spared, and there is significant retention of binding within the olfactory bulb and nucleus and neocortex. We did not observe any deficits in the general health, sensorimotor functions, anxiety-like behaviors, or sucrose intake in either Oxtr(-/-) or Oxtr(FB/FB) mice. Females of both KO types deliver pups, but only the Oxtr(FB/FB) mice are able to eject milk. Oxtr(-/-) males show impaired social memory for familiar females, whereas the Oxtr(FB/FB) males appear to recognize their species but not individuals. Our results confirm the importance of oxytocin in social recognition and demonstrate that spatial and temporal inactivation of the Oxtr will enable finer understanding of the physiological, behavioral, and developmental roles of the receptor. C1 [Lee, Heon-Jin; Caldwell, Heather K.; Macbeth, Abbe H.; Tolu, Selen G.; Young, W. Scott] NIMH, Dept Hlth & Human Services, Sect Neural Gene Express 3, NIH, Bethesda, MD 20892 USA. RP Young, WS (reprint author), 3rd Bldg 49,Room 5A51,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wsy@mail.nih.gov RI Young, W Scott/A-9333-2009; OI Young, W Scott/0000-0001-6614-5112; , Heon-Jin/0000-0002-1911-5014 FU Intramural NIH HHS; NIMH NIH HHS [Z01 MH002498, Z01 MH 002498-17] NR 41 TC 94 Z9 96 U1 2 U2 10 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 JUL PY 2008 VL 149 IS 7 BP 3256 EP 3263 DI 10.1210/en.2007-1710 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 319LS UT WOS:000257165700004 PM 18356275 ER PT J AU Lu, CX Willingham, MC Furuya, F Cheng, SY AF Lu, Changxue Willingham, Mark C. Furuya, Fumihiko Cheng, Sheue-Yann TI Activation of phosphatidylinositol 3-kinase signaling promotes aberrant pituitary growth in a mouse model of thyroid-stimulating hormone-secreting pituitary tumors SO ENDOCRINOLOGY LA English DT Article ID AKT ACTIVATION; BETA-RECEPTOR; ADENOMAS; PATHWAY; GENE; BAD; CARCINOMA; CANCER; DEATH; PHOSPHORYLATION AB TSH-secreting pituitarytumors(TSHomas) are pituitarytumors that constitutively secrete TSH. Molecular mechanisms underlying this abnormality are largely undefined. We recently created a knock-in mutant mouse harboring a mutation (denoted as PV) in the thyroid hormone receptor-beta gene (TR beta(PV/PV) mouse). As these mice age, they spontaneously develop TSHomas. Using this mouse model, we investigated the role of the phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway in the pathogenesis of TSHomas. Concurrent with aberrant growth of pituitaries, AKT and its downstream effectors, mammalian target rapamycin and p70(S6K), were activated to contribute to increased cell proliferation and pituitary growth. In addition, activation of AKT led to decreased apoptosis by inhibiting proapoptotic activity of Bcl-2-associated death promoter, further contributing to the aberrant cell proliferation. These results suggest an activated PI3K-AKT pathway could underscore tumorigenesis, raising the possibility that this pathway could be a potential therapeutic target in TSHomas. Indeed, TR beta(PV/ PV) mice treated with a PI3K-specific inhibitor, LY294002, showed a significant decrease in pituitary growth. The progrowth signaling via AKT-mammalian target rapamycinp-70(S6K) and cyclin D1/cyclin-dependent kinase were inhibited, and proapoptotic activity of Bcl-2-associated death promoter was increased by LY294002 treatment. Thus, activation of the PI3K-AKT pathway mediates, at least in part, the aberrant pituitary growth, and the intervention of this signaling pathway presents a novel therapeutic opportunity for TSHomas. C1 [Lu, Changxue; Furuya, Fumihiko; Cheng, Sheue-Yann] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Willingham, Mark C.] Wake Forest Univ, Dept Pathol, Winston Salem, NC 27157 USA. RP Cheng, SY (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37,Room 5128,37 Convent Dr MSC 4264, Bethesda, MD 20892 USA. EM chengs@mail.nih.gov FU Intramural NIH HHS NR 34 TC 25 Z9 28 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 JUL PY 2008 VL 149 IS 7 BP 3339 EP 3345 DI 10.1210/en.2007-1696 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 319LS UT WOS:000257165700015 PM 18356276 ER PT J AU Constantin, S Wray, S AF Constantin, Stephanie Wray, Susan TI Gonadotropin-releasing hormone-1 neuronal activity is independent of hyperpolarization-activated cyclic nucleotide-modulated channels but is sensitive to protein kinase A-dependent phosphorylation SO ENDOCRINOLOGY LA English DT Article ID EMBRYONIC OLFACTORY PLACODE; GREEN FLUORESCENT PROTEIN; SINOATRIAL NODE CELLS; GNRH NEURONS; TRANSGENIC MICE; MEMBRANE-PROPERTIES; SIGNALING PATHWAY; COUPLED RECEPTORS; CA2+ OSCILLATIONS; EXPLANT CULTURES AB Pulsatile release of GnRH-1 stimulates the anterior pituitary and induces secretion of gonadotropin hormones. GnRH-1 release is modulated by many neurotransmitters that act via G protein-coupled membrane receptors. cAMP is the most ubiquitous effector for these receptors. GnRH-1 neurons express hyperpolarization-activated cyclic nucleotide-modulated (HCN) channel protein in vivo. HCN channels are involved in neuronal pacemaking and can integrate cAMP signals. cAMP-dependent protein kinase (PKA) is also activated by cAMP signals, and PKA-dependent phosphorylation modulates voltage-activated channels. In this report, these two pathways were examined in GnRH-1 neurons as integrators of forskolin (FSK)-induced stimulation. The HCN3 isoform was detected in GnRH-1 neurons obtained from mouse nasal explants. ZD7288, a HCN channel blocker, significantly reduced the efficiency of FSK to stimulate GnRH-1 neurons, whereas blockade of PKA with Rp-adenosine-3',5'-cyclic monophosphorothioate triethylammonium did not attenuate the FSK-induced stimulation. To ensure that disruption of HCN channels on GnRH-1 neurons was responsible for reduction of FSK stimulation, experiments were performed removing gamma-aminobutyric acid (GABA), the major excitatory input to GnRH-1 neurons in nasal explants. Under these conditions, Rp-adenosine-3',5'-cyclic monophosphorothioate triethylammonium, but not ZD7288, altered the FSK-induced response of GnRH-1 neurons. These studies indicate that PKA-dependent phosphorylation is involved in the FSK-induced stimulation of GnRH-1 neurons rather than HCN channels, and HCN channels integrate the FSK-induced stimulation on GABAergic neurons. In addition, blockade of HCN channels did not modify basal GnRH-1 neuronal activity when GABAergic input was intact or removed, negating a role for these channels in basal GABAergic or GnRH-1 neuronal activity. C1 NIH, Natl Inst Neurol Disorders & Stroke, Cellular & Dev Neurobiol Sect, Bethesda, MD 20892 USA. RP Wray, S (reprint author), NIH, Natl Inst Neurol Disorders & Stroke, Cellular & Dev Neurobiol Sect, Bethesda, MD 20892 USA. EM wrays@ninds.nih.gov RI Constantin, Stephanie/C-5264-2009; OI Constantin, Stephanie/0000-0003-0596-9737; wray, susan/0000-0001-7670-3915 FU Intramural NIH HHS NR 73 TC 13 Z9 13 U1 0 U2 2 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 2008 VL 149 IS 7 BP 3500 EP 3511 DI 10.1210/en.2007-1508 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 319LS UT WOS:000257165700032 PM 18372334 ER PT J AU Liu, Y Kamitakahara, A Kim, AJ Aguilera, G AF Liu, Ying Kamitakahara, Anna Kim, Alice Joohee Aguilera, Greti TI Cyclic adenosine 3 ',5 '-monophosphate responsive element binding protein phosphorylation is required but not sufficient for activation of corticotropin releasing hormone transcription SO ENDOCRINOLOGY LA English DT Article ID HYPOTHALAMIC CELL-LINE; GENE-EXPRESSION; PARAVENTRICULAR NUCLEUS; ADRENOCORTICOTROPIN SECRETION; MESSENGER-RNA; ATT-20 CELLS; STRESS; GLUCOCORTICOIDS; VASOPRESSIN; MECHANISMS AB cAMP is a major regulator of CRH transcription. However, receptors activating CRH neurons (alpha-adrenergic and glutamatergic) do not signal through cAMP, suggesting that calcium phospholipid-dependent signaling synergizes with small elevations of intracellular cAMP. To test this hypothesis, we examined the relationship between activation of CRH transcription, cAMP production, and cAMP response element binding protein (CREB) phosphorylation in neuronal cultures treated with the adenylyl cyclase stimulator, forskolin, the phorbol ester, phorbol-12-myristate-13-acetate (PMA), or their combination. Forskolin, at threshold concentrations for cAMP production and CREB phosphorylation, induced CRH promoter-driven luciferase activity in 4B cells (EC(50) = 0.7 mu M) and CRH primary transcript in hypothalamic neurons (EC50 = 0.6 mu M). PMA alone failed to activate CRH transcription despite being as effective as forskolin in phosphorylating CREB (Ser133 and Ser121). Although PMA potentiated the effect of low forskolin concentrations on CRH transcription and CREB phosphorylation, there was no correlation between phosphorylated CREB levels and activation of CRH transcription. Similarly, the calcium/calmodulin-dependent kinase inhibitor, KN-93, enhanced PMA plus forskolin-stimulated CREB phosphorylation and inhibited CRH transcription. Suppression of CREB phosphorylation by the protein kinase A inhibitor, H89, or the CREB dominant negative, A-CREB, did not affect basal but blocked forskolin-stimulated transcription. This study shows that calcium phospholipid-dependent pathways potentiate the ability of small elevations of intracellular cAMP to activate CRH transcription, providing a mechanism by which non-cAMP-dependent regulators induce CRH gene expression. In addition, the data indicate that phosphorylated CREB is essential but not sufficient for activation of CRH transcription, suggesting that full promoter stimulation requires the interaction of phosphorylated CREB with a coactivator. C1 NICHHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Aguilera, G (reprint author), NICHHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH, Bldg 10,Room 11E-3330,10 Ctr Dr, Bethesda, MD 20892 USA. EM greti_aguilera@nih.gov FU Intramural NIH HHS NR 36 TC 36 Z9 36 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 JUL PY 2008 VL 149 IS 7 BP 3512 EP 3520 DI 10.1210/en.2008-0052 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 319LS UT WOS:000257165700033 PM 18372325 ER PT J AU Shen, M Zhang, LP Bonner, MR Liu, CS Li, GL Vermeulen, R Dosemeci, M Yin, SN Lan, Q AF Shen, Min Zhang, Luoping Bonner, Matthew R. Liu, Chin-San Li, Guilan Vermeulen, Roel Dosemeci, Mustafa Yin, Songnian Lan, Qing TI Association between mitochondrial DNA copy number, blood cell counts, and occupational benzene exposure SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE benzene; mitochondrial DNA; oxidative stress ID OXIDATIVE STRESS; INDUCED APOPTOSIS; PROGENITOR CELLS; SKELETAL-MUSCLE; METABOLITES; TOXICITY; INCREASE; DAMAGE; HEART; HL-60 AB Benzene is a recognized hematotoxicant and carcinogen that produces genotoxic damage. Benzene metabolites can produce reactive oxidative species. Mitochondrial DNA (mtDNA) copy number may be increased in response to oxidative stress to compensate for damaged mitochondria. We carried out a cross-sectional study of 40 benzene-exposed workers and 40 controls to evaluate the association between benzene exposure and mtDNA copy number. Copy number of mtDNA in leukocyte DNA was determined by real-time PCR. Compared with controls, the copy number of mtDNA increased by 4% and by 15% in workers exposed to <= 10 ppm (n = 20) and >10 ppm (n = 20) benzene, respectively. After adjusting for recent infection, the factor that was significantly correlated with mtDNA, the increase of mtDNA was statistically significant in the high exposed group (P = 0.016) with a significant linear trend (P = 0.024). To our best knowledge, this is the first report that benzene exposure was associated with increased mitochondria DNA copy number. Benzene exposure may induce mtDNA amplification, possibly in response to oxidative stress caused by benzene. The finding needs to be replicated by other studies. C1 [Shen, Min; Dosemeci, Mustafa; Lan, Qing] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH DHHS, Bethesda, MD 20892 USA. [Zhang, Luoping] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Bonner, Matthew R.] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. [Liu, Chin-San] Changhua Christian Hosp, Dept Neurol, Changhua, Taiwan. [Liu, Chin-San] Changhua Christian Hosp, Vasc & Genom Ctr, Changhua, Taiwan. [Li, Guilan; Yin, Songnian] Chinese Ctr Dis Control & Prevent, Inst Occupat Hlth & Poison Control, Beijing, Peoples R China. [Vermeulen, Roel] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands. RP Shen, M (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH DHHS, MSC 7240,6120 Execut Blvd, Bethesda, MD 20892 USA. EM shenmi@mail.nih.gov RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 FU Intramural NIH HHS [NIH0011547510, ZIA CP010120-14]; NIEHS NIH HHS [P42 ES004705, P30 ES001896, P30 ES010126, P30ES01896, P30ES10126, P42 ES005948, P42ES04705, P42ES05948, R01 ES006721, R01ES06721] NR 21 TC 25 Z9 25 U1 0 U2 3 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 JUL PY 2008 VL 49 IS 6 BP 453 EP 457 DI 10.1002/em.20402 PG 5 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 330ZA UT WOS:000257980200005 PM 18481315 ER PT J AU Cowin, PA Foster, P Pedersen, J Hedwards, S McPherson, SJ Risbridger, GA AF Cowin, Prue A. Foster, Paul Pedersen, John Hedwards, Shelley McPherson, Stephen J. Risbridger, Gail A. TI Early-onset endocrine disruptor-induced prostatitis in the rat SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE antiandrogen; endocrine disruptors; inflammation; prostate; prostatitis; vinclozolin ID QUALITY-OF-LIFE; BRANCHING MORPHOGENESIS; PUBERTAL DEVELOPMENT; NEONATAL EXPOSURE; VINCLOZOLIN; ESTROGENS; ANDROGENS; CANCER; GLAND; DIFFERENTIATION AB BACKGROUND: Androgens are critical for specifying prostate development, with the fetal prostate sensitive to altered hormone levels and endocrine-disrupting chemicals (EDCs) that exhibit estrogenic or antiandrogenic properties. Prostatic inflammation (prostatitis) affects 9% of men of all ages, and > 90% of cases are of unknown etiology. OBJECTIVE: In this study we aimed to evaluate effects of in utero exposure to the antiandrogenic EDC vinclozolin, during the period of male reproductive tract: development, on neonatal, prepubertal, and postpubertal prostate gland function of male offspring. METHODS: Fetal rats were exposed to vinclozolin (100 mg/kg body weight) or vehicle control (2.5 mL/kg body weight) in utero from gestational day 14 (GD14) to GD19 via oral administration to pregnant dams. Tissue analysis was carried out when male offspring were 0, 4, or 8 weeks of age. RESULTS: In utero exposure to vinclozolin was insufficient to perturb prostatic development and branching, although expression of androgen receptor and mesenchymal fibroblast growth factor-10 was down-regulated. Prostate histology remained normal until puberty, but 100% of animals displayed prostatitis postpubertally (56 days of age). Prostatic inflammation was associated with phosphorylation and nuclear translocation of nuclear factor-kappa B (NF kappa B) and postpubertal activation of proinflammatory NF kappa B-dependent genes, including the chemokine interleukin-8 an the cytokine transforming growth factor-beta 1. Significantly, inflammation arising from vinclozolin exposure was not associated with the emergence of premalignant lesions, such as prostatic intraepithelial neoplasia or proliferative inflammatory atrophy, and hence mimics nonbacterial early-onset prostatitis that commonly occurs in young men. CONCLUSIONS: These data are the first to unequivocally implicate EDCs as a causative factor and fill an important knowledge gap on the etiology of prostatitis. C1 [Cowin, Prue A.; Hedwards, Shelley; McPherson, Stephen J.; Risbridger, Gail A.] Monash Univ, Monash Inst Med Res, Ctr Urol Res, Clayton, Vic 3168, Australia. [Foster, Paul] Natl Inst Environm Hlth, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. [Pedersen, John] Tissupath Labs, Hawthorn, Vic, Australia. RP Risbridger, GA (reprint author), Monash Med Ctr, Monash Inst Med Res, 246 Clayton Rd, Clayton, Vic 3168, Australia. EM Gail.Risbridger@med.monash.edu.au RI McPherson, Stephen/A-9490-2009; Risbridger, Gail/B-8655-2008 OI Risbridger, Gail/0000-0003-3089-4028 FU Intramural NIH HHS NR 41 TC 25 Z9 28 U1 0 U2 4 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 JUL PY 2008 VL 116 IS 7 BP 923 EP 929 DI 10.1289/ehp.11239 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 319ST UT WOS:000257185000036 PM 18629315 ER PT J AU Kamel, F Umbach, DM Stallone, L Richards, M Hu, H Sandler, DP AF Kamel, Freya Umbach, David M. Stallone, Lillian Richards, Marie Hu, Howard Sandler, Dale P. TI Association of lead exposure with survival in amyotrophic lateral sclerosis SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE amyotrophic lateral sclerosis; lead; prognosis; survival ID MOTOR-NEURON DISEASE; POPULATION; MORTALITY; PROGRESSION; DIAGNOSIS; ACCURACY; UTILITY; GENES; BONE AB BACKGROUND: Reasons for the variability in survival among ALS cases are unknown but may include exposure to environmental neurotoxicants. OBJECTIVES: We aimed to determine whether lead exposure, assessed by measuring blood and bone lead levels, is associated with survival in amyotrophic lateral sclerosis (ALS). METHODS: We evaluated the relationship of lead exposure to ALS survival in 110 cases from a case-control study conducted in New England in 1993-1996 that included measurements of blood and bone lead. We retrieved information on date and cause of death through 31 December 2003 from the National Death Index Plus and the Social Security Administration Death Index. We evaluated the relationship of survival to lead exposure using Cox proportional hazard analysis, with adjustment for age, sex, and smoking. RESULTS: We found mortality data for 100 of 110 cases; 93 of 100 death certificates mentioned ALS. Median survival from diagnosis to death was 28 months. Shorter survival was associated with older age at diagnosis, female sex, bulbar onset, shorter interval between symptom onset and diagnosis, and reduced lung function. Shorter survival from diagnosis to death had a weak inverse association with blood lead (hazard ratio = 0.9; 95% confidence interval, 0.8-1.0) and a stronger inverse association with patella lead (0.5; 0.2-1.0) and tibia lead (0.3; 0.1-0.7); similar results were found for survival from symptom onset to death. CONCLUSIONS: These results suggest that lead exposure is associated with longer survival in ALS cases and, if confirmed, may shed light on mechanisms involved in disease progression. C1 [Kamel, Freya; Sandler, Dale P.] NIEHS, NIH, Dept Hlth & Human Serv, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Umbach, David M.] NIEHS, NIH, Dept Hlth & Human Serv, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Stallone, Lillian] Social & Sci Syst Inc, Durham, NC USA. [Richards, Marie] Westat Corp, Durham, NC USA. [Hu, Howard] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. RP Kamel, F (reprint author), NIEHS, NIH, Dept Hlth & Human Serv, Epidemiol Branch, POB 12233, Res Triangle Pk, NC 27709 USA. EM kamel@niehs.nih.gov OI Kamel, Freya/0000-0001-5052-6615; Sandler, Dale/0000-0002-6776-0018 FU Intramural NIH HHS NR 32 TC 23 Z9 24 U1 1 U2 1 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUL PY 2008 VL 116 IS 7 BP 943 EP 947 DI 10.1289/ehp.11193 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 319ST UT WOS:000257185000039 PM 18629318 ER PT J AU Arbuckle, TE Hauser, R Swan, SH Mao, CS Longnecker, MP Main, KM Whyatt, RM Mendola, P Legrand, M Rovet, J Till, C Wade, M Jarrell, J Matthews, S Van Vliet, G Bornehag, CG Mieusset, R AF Arbuckle, Tye E. Hauser, Russ Swan, Shanna H. Mao, Catherine S. Longnecker, Matthew P. Main, Katharina M. Whyatt, Robin M. Mendola, Pauline Legrand, Melissa Rovet, Joanne Till, Christine Wade, Mike Jarrell, John Matthews, Stephen Van Vliet, Guy Bornehag, Carl-Gustaf Mieusset, Roger TI Meeting report: Measuring endocrine-sensitive endpoints within the first years of life SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE anogenital distance; anthropometry; endocrine disruptors; genital exam; hormones; infants; measurement; neurodevelopment; reproductive tract development; sexual dimorphism ID ANOGENITAL DISTANCE; MALE NEWBORNS; INFANTS; DIFFERENCE; ESTRADIOL; DECREASE; EXPOSURE; HORMONE; CHIAPAS; MEXICO AB An international workshop tided "Assessing Endocrine-Related Endpoints within the First Years of Life" was held 30 April-1 May 2007, in Ottawa, Ontario, Canada. Representatives from a number of pregnancy cohort studies in North America and Europe presented options for measuring various endocrine-sensitive endpoints in early life and discussed issues related to performing and using those measures. The workshop focused on measuring reproductive tract developmental endpoints [e.g., anogenital distance (AGD)], endocrine status, and infant anthropometry. To the extent possible, workshop participants strove to develop or recommend standardized measurements that would allow comparisons and pooling of data across studies. The recommended outcomes include thigh fat fold, breast size, vaginal cytology, AGD, location of the testis, testicular size, and growth of the penis, with most of the discussion focusing on the genital exam. Although a number of outcome measures recommended during the genital exam have been associated with exposure to endocrine-disrupting chemicals, little is known about how predictive these effects are of later reproductive health or other chronic health conditions. C1 [Arbuckle, Tye E.] Healthy Environm & Consumer Safety Branch, Biostatist & Epidemiol Div, Ottawa, ON K1A 0K9, Canada. [Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Swan, Shanna H.] Univ Rochester, Med Ctr, Sch Med & Dent, Rochester, NY 14642 USA. [Mao, Catherine S.] Harbor UCLA Med Ctr, Torrance, CA 90509 USA. [Longnecker, Matthew P.] Natl Inst Environm Hlth Sci, NIH, Epidemiol Branch, Res Triangle Pk, NC USA. [Longnecker, Matthew P.] Univ Copenhagen, Rigshosp, Dept Growth & Reprod, DK-2100 Copenhagen, Denmark. [Whyatt, Robin M.] Columbia Univ, Childrens Ctr Environm Hlth, New York, NY USA. [Mendola, Pauline] US EPA, Natl Hlth & Environm Effects Res Lab, Chapel Hill, NC USA. [Legrand, Melissa] Hlth Canada, Environm Hlth Surveillance Div, Ottawa, ON K1A 0L2, Canada. [Rovet, Joanne] Hosp Sick Children, Neurosci & Mental Hlth Program, Toronto, ON M5G 1X8, Canada. [Till, Christine] Hosp Sick Children, Dept Psychol, Toronto, ON M5G 1X8, Canada. [Wade, Mike] Hlth Canada, Environm Hlth Sci & Res Bur, Ottawa, ON K1A 0L2, Canada. [Jarrell, John] Univ Calgary, Dept Obstet & Gynecol, Calgary, AB, Canada. [Matthews, Stephen] Univ Toronto, Dept Physiol, Toronto, ON, Canada. [Bornehag, Carl-Gustaf] Univ Montreal, Dept Pediat, Montreal, PQ H3C 3J7, Canada. [Bornehag, Carl-Gustaf] Tech Univ Denmark, Dept Mech Engn, DK-2800 Lyngby, Denmark. [Mieusset, Roger] Univ Male Steril Ctr, Toulouse, France. RP Arbuckle, TE (reprint author), Healthy Environm & Consumer Safety Branch, Biostatist & Epidemiol Div, Ottawa, ON K1A 0K9, Canada. EM arbuckle@hc-sc.gc.ca OI Wade, Michael/0000-0002-7331-3839; Longnecker, Matthew/0000-0001-6073-5322; Mendola, Pauline/0000-0001-5330-2844 FU Intramural NIH HHS NR 20 TC 17 Z9 20 U1 1 U2 6 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUL PY 2008 VL 116 IS 7 BP 948 EP 951 DI 10.1289/ehp.11226 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 319ST UT WOS:000257185000040 PM 18629319 ER PT J AU Linet, MS AF Linet, Martha S. TI The search for environmental effects on children's health SO EPIDEMIOLOGY LA English DT Editorial Material ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; NERVOUS-SYSTEM; MARIJUANA; LEUKEMIA; EXPOSURE; SAMPLE; RISK AB The report by Divan et al linking early exposures to cell phones with behavioral problems in young children, published in this issue of EPIDEMIOLOGY, provides an opportunity to consider pursuit of high-risk hypotheses that could open new areas of understanding in contrast with the more common assessment of lower-risk leads. Other key considerations for epidemiologists are the requirements for selecting plausible risk factors while remaining alert to serendipitous discovery, for validating proxy measures of complex disease outcomes and exposures, and for pursuing replication of unexpected results in independent settings. In the face of unexpected findings, research consortia provide opportunities for pursuing exploratory and follow-up studies of high-risk hypotheses. C1 NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. RP Linet, MS (reprint author), NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, 6120 Execut Blvd,EPS Room 7048, Bethesda, MD 20892 USA. EM linetm@mail.nih.gov FU Intramural NIH HHS NR 15 TC 1 Z9 1 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2008 VL 19 IS 4 BP 530 EP 531 DI 10.1097/EDE.0b013e31817ae59d PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 315GB UT WOS:000256865100002 PM 18497700 ER PT J AU Mujahid, MS Roux, AVD Morenoff, JD Raghunathan, TE Cooper, RS Ni, HY Shea, S AF Mujahid, Mahasin S. Roux, Ana V. Diez Morenoff, Jeffrey D. Raghunathan, Trivellore E. Cooper, Richard S. Ni, Hanyu Shea, Steven TI Neighborhood characteristics and hypertension SO EPIDEMIOLOGY LA English DT Article ID MULTILEVEL LOGISTIC-REGRESSION; CORONARY-HEART-DISEASE; BLOOD-PRESSURE; ENVIRONMENTAL-FACTORS; ATHEROSCLEROSIS RISK; SOCIAL EPIDEMIOLOGY; PHYSICAL-ACTIVITY; HEALTH; ASSOCIATIONS; COMMUNITIES AB Background: The goal of this study was to investigate cross-sectional associations between features of neighborhoods and hypertension and to examine the sensitivity of results to various methods of estimating neighborhood conditions. Methods: We used data from the Multi-Ethnic Study of Atherosclerosis on 2612 individuals 45-85 years of age. Hypertension was defined as systolic blood pressure above 140 mm Hg, diastolic pressure above 90 mm Hg, or use of antihypertensive medications. Neighborhood (census tract) conditions potentially related to hypertension (walking environment, availability of healthy foods, safety, social cohesion) were measured using information from a separate phone survey conducted in the study neighborhoods. For each neighborhood we estimated scale scores by aggregating residents' responses using simple aggregation (crude means) and empirical Bayes estimation (unconditional, conditional, and spatial). These estimates of neighborhood conditions were linked to each study participant based on the census tract of residence. Two-level binomial regression methods were used to estimate adjusted associations between neighborhood conditions and hypertension. Results: Residents of neighborhoods with better walkability, availability of healthy foods, greater safety, and more social cohesion were less likely to be hypertensive (relative prevalence [95% confidence interval] for 90th vs. 10th percentile of conditional empirical Bayes estimate = 0.75 [0.64-0.88], 0.72 [0.61-0.85], 0.74 [0.63-0.86], and 0.69 [0.57-0.83]), respectively, after adjusting for site, age, sex, income, and education. Associations were attenuated and often disappeared after additional adjustments for race/ethnicity. Conclusion: Neighborhood walkability, food availability, safety, and social cohesion may be mechanisms that link neighborhoods to hypertension. C1 [Mujahid, Mahasin S.; Roux, Ana V. Diez] Univ Michigan, Sch Publ Hlth, Ctr Social Epidemiol & Populat Hlth, Ann Arbor, MI 48104 USA. [Morenoff, Jeffrey D.] Univ Michigan, Coll Literature Sci & Arts, Dept Sociol, Ann Arbor, MI 48109 USA. [Raghunathan, Trivellore E.] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. [Cooper, Richard S.] Loyola Univ, Dept Prevent Med, Chicago, IL 60611 USA. [Ni, Hanyu] NHLBI, NIH, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. [Shea, Steven] Columbia Univ, Dept Med, New York, NY USA. [Shea, Steven] Columbia Univ, Dept Epidemiol, New York, NY USA. RP Roux, AVD (reprint author), Univ Michigan, Sch Publ Hlth, Ctr Social Epidemiol & Populat Hlth, 109 Observ St Rm 3671, Ann Arbor, MI 48104 USA. EM adiezrou@umich.edu RI Morenoff, Jeffrey/E-9800-2015 OI Morenoff, Jeffrey/0000-0002-8146-8590 FU NHLBI NIH HHS [N01-HC-951565, N01-HC-951561, N01-HC-951562, N01-HC-951560, N01-HC-951563, N01-HC-951564, N01-HC-95159, N01-HC-95169, R01 HL071759] NR 40 TC 111 Z9 113 U1 3 U2 20 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2008 VL 19 IS 4 BP 590 EP 598 DI 10.1097/EDE.0b013e3181772cd2 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 315GB UT WOS:000256865100015 PM 18480733 ER PT J AU Lie, RT Wilcox, AJ Taylor, J Gjessing, HK Saugstad, OD Aabyholm, F Vindenes, H AF Lie, Rolv T. Wilcox, Allen J. Taylor, Jack Gjessing, Hakon K. Saugstad, Ola Didrik Aabyholm, Frank Vindenes, Halvard TI Maternal smoking and oral clefts - The role of detoxification pathway genes SO EPIDEMIOLOGY LA English DT Article ID SINGLE NUCLEOTIDE POLYMORPHISMS; CASE-PARENT TRIADS; OROFACIAL CLEFTS; CIGARETTE-SMOKING; HUMAN N-ACETYLTRANSFERASE-2; POPULATION STRATIFICATION; RISK; VARIANTS; ENZYMES; CANCER AB Background: There is evidence for an effect of cigarette smoking on risk of oral clefts. There are also hypothetical pathways for a biologic effect involving toxic chemicals in cigarette smoke. Methods: We performed a combined case-control and family-triad study of babies born with oral clefts in Nor-way in the period 1996 to 2001, with 88% participation among cases (n = 573) and 76% participation among controls (n = 763). Mothers completed a questionnaire 4 months after birth of the baby. DNA was collected from parents and children, and assayed for genes related to detoxification of compounds of cigarette smoke (NAT1, NAT2, CYP1A1, GSTP1, GSTT1, and GSTM1). Results: For isolated cleft lip (with or without cleft palate) there was a dose-response effect of smoking in the first trimester. The odds ratio rose from 1.6 (95% confidence interval = 1.0-2.5) for passive smoking to 1.9 (0.9-4.0) for mothers who smoked more than 10 cigarettes per day. There was little evidence of an association with cleft palate. Genetic analyses used both case-control and family-triad data. In case-triads we found an association between a NAT2 haplotype and isolated cleft lip (relative risk of 1.6 with 1 copy of the allele and 2.5 with 2 copies), but with little evidence of interaction with smoking. Other genes did not show associations, and previously described interactions with smoking were not confirmed. Conclusion: First-trimester smoking was clearly associated with risk of cleft lip. This effect was not modified by variants of genes related to detoxification of compounds of cigarette smoke. C1 [Lie, Rolv T.; Gjessing, Hakon K.] Univ Bergen, Dept Publ Hlth & Primary Hlth Care, N-5018 Bergen, Norway. [Lie, Rolv T.] Norwegian Inst Publ Hlth, Med Birth Registry Norway, Bergen, Norway. [Wilcox, Allen J.; Taylor, Jack] NIEHS, Epidemiol Branch, Durham, NC USA. [Gjessing, Hakon K.] Norwegian Inst Publ Hlth, Oslo, Norway. [Saugstad, Ola Didrik] Univ Oslo, Natl Hosp, Dept Pediat, Oslo, Norway. [Aabyholm, Frank] Univ Oslo, Natl Hosp, Dept Plast Surg, Oslo, Norway. [Vindenes, Halvard] Haukeland Hosp, Dept Plast Surg, N-5021 Bergen, Norway. RP Lie, RT (reprint author), Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Kalfarveien 31, N-5018 Bergen, Norway. EM rolv.lie@smis.uib.no RI Gjessing, Hakon/A-5871-2012; OI Wilcox, Allen/0000-0002-3376-1311; taylor, jack/0000-0001-5303-6398 FU Intramural NIH HHS; NIDCR NIH HHS [2R01 DE-11948-04] NR 36 TC 40 Z9 46 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2008 VL 19 IS 4 BP 606 EP 615 DI 10.1097/EDE.0b013e3181690731 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 315GB UT WOS:000256865100017 PM 18449058 ER PT J AU Harel, O Schisterman, EF Vexler, A Ruopp, MD AF Harel, Ofer Schisterman, Enrique F. Vexler, Albert Ruopp, Marcus D. TI Monitoring quality control - Can we get better data? SO EPIDEMIOLOGY LA English DT Article AB Quality control is important in many fields, especially industrial production. Major research has been developed with regard to industrial quality control to ensure reliable and consistent products. We adapt and develop methodology in quality control to monitor data collection in epidemiologic studies. There are no procedures currently used-by epidemiologists to evaluate quality control during the actual process of data collection; methods are implemented only after the data have been collected. We focus on procedures that can be used during data collection: instrument calibration and population sampling. For the first, we propose methods utilizing Shewhart control charts and Westgard stopping rules. For evaluating population sampling, we present methods utilizing regression analysis. We provide a motivating example to highlight the utility of these methods. The proposed methodology may help investigators to identify data quality problems that can be corrected while data are still being collected, and also to identify biases in data collection that might be adjusted later. C1 [Schisterman, Enrique F.; Vexler, Albert; Ruopp, Marcus D.] NICHD NIH DHHS, Rockville, MD USA. [Harel, Ofer] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. RP Schisterman, EF (reprint author), NICHD NIH DHHS, Rockville, MD USA. EM schistee@mail.nih.gov OI Schisterman, Enrique/0000-0003-3757-641X FU Intramural NIH HHS [Z01 HD008795-01]; NIMH NIH HHS [K01 MH087219] NR 12 TC 6 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2008 VL 19 IS 4 BP 621 EP 627 DI 10.1097/EDE.0b013e318176bfb2 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 315GB UT WOS:000256865100019 PM 18496467 ER PT J AU Howards, PP Schisterman, EF AF Howards, Penelope P. Schisterman, Enrique F. TI Confounding by exposure history and prior outcome - The authors respond SO EPIDEMIOLOGY LA English DT Letter C1 [Howards, Penelope P.] Emory Univ, Dept Epidemiol, Atlanta, GA 30322 USA. [Schisterman, Enrique F.] NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. RP Howards, PP (reprint author), Emory Univ, Dept Epidemiol, Atlanta, GA 30322 USA. EM penelope.howards@emory.edu NR 2 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2008 VL 19 IS 4 BP 636 EP 636 DI 10.1097/EDE.0b013e31817734a6 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 315GB UT WOS:000256865100024 ER PT J AU White, HS Franklin, MR Kupferberg, HJ Schmutz, M Stables, JP Wolf, HH AF White, H. Steve Franklin, Michael R. Kupferberg, Harvey J. Schmutz, Markus Stables, James P. Wolf, Harold H. TI The anticonvulsant profile of rufinamide (CGP 33101) in rodent seizure models SO EPILEPSIA LA English DT Article DE antiepileptic drug; maximal electroshock test; pentylenetetrazol test; rufinamide ID ANTIEPILEPTIC DRUGS; MICE AB Purpose: To evaluate the anticonvulsant profile and behavioral toxicity of rufinamide in animal seizure models compared to the established antiepileptic drugs (AEDs): phenytoin, phenobarbital, valproate, and ethosuximide, or vehicle. Methods: In acute studies of anticonvulsant efficacy, the AEDs were administered via oral (CF1 mice and Sprague-Dawley rats) and intraperitoneal (CF1 mice) routes. The AEDs were assessed for their ability to inhibit seizures induced by maximal electroshock (MES) or subcutaneous pentylenetetrazol, and ability to block seizures induced by subcutaneous strychnine, bicuculline, or picrotoxin. Tolerance of oral rufinamide was assessed in rats following 5-day (versus single-dose) treatment with oral rufinamide using the dose equivalent necessary to achieve a 50% decrease in seizure frequency (ED(50)). Metabolic tolerance was also evaluated using an in vitro liver microsomal assay. Results: Oral rufinamide suppressed pentylenetetrazol-induced seizures in mice (ED(50) 45.8 mg/kg) but not rats, and was active against MES-induced tonic seizures in mice (ED(50) 23.9 mg/kg) and rats (ED(50) 6.1 mg/kg). Intraperitoneal rufinamide suppressed pentylenetetrazol-, bicuculline-, and picrotoxin-induced clonus in mice (ED(50) 54.0, 50.5, and 76.3 mg/kg, respectively). Rufinamide was partially effective in the mouse strychnine test. The behavioral toxicity of rufinamide was similar to or better than established AEDs tested in this study. In general, the protective index of rufinamide was greater than that of the other AEDs. Conclusions: The efficacy and behavioral toxicity profiles in these animal models suggest that rufinamide may be effective in the treatment of generalized and partial seizures. C1 [White, H. Steve] Univ Utah, Dept Pharmacol & Toxicol, Anticonvulsant Drug Dev Program, Salt Lake City, UT 84108 USA. [Kupferberg, Harvey J.; Stables, James P.] Natl Inst Hlth, Bethesda, MD USA. [Schmutz, Markus] Novartis Pharma AG, Basel, Switzerland. RP White, HS (reprint author), Univ Utah, Dept Pharmacol & Toxicol, Anticonvulsant Drug Dev Program, 417 Wakara Way,Suite 3211, Salt Lake City, UT 84108 USA. EM swhite@hsc.utah.edu NR 18 TC 34 Z9 35 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JUL PY 2008 VL 49 IS 7 BP 1213 EP 1220 DI 10.1111/j.1528-1167.2008.01552.x PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 326KV UT WOS:000257658600012 PM 18325020 ER PT J AU Cui, L Miao, J Furuya, T Fan, Q Li, XY Rathod, PK Su, XZ Cui, LW AF Cui, Long Miao, Jun Furuya, Tetsuya Fan, Qi Li, Xinyi Rathod, Pradipsinh K. Su, Xin-zhuan Cui, Liwang TI Histone acetyltransferase inhibitor anacardic acid causes changes in global gene expression during in vitro Plasmodium falciparum development SO EUKARYOTIC CELL LA English DT Article ID SACCHAROMYCES-CEREVISIAE; CHROMATIN TRANSCRIPTION; MALARIA PARASITES; ANTIFUNGAL AGENTS; CANDIDA-ALBICANS; VIRULENCE GENES; ACETYLATION; CURCUMIN; P300; REPRESSES AB To better understand the role of histone lysine acetylation in transcription in Plasmodium falciparum, we sought to attenuate histone acetyltransferase (HAT) activity using anacardic acid (AA). We showed that AA reversibly and noncompetitively inhibited the HAT activity of recombinant PfGCN5. To a lesser extent, AA inhibited the PfGCN5 activity in parasite nuclear extracts but did not affect histone deacetylase activity. AA blocked the growth of both chloroquine-sensitive and -resistant strains, with a 50% inhibitory concentration of similar to 30 mu M. Treatment of the parasites with 20 mu M of AA for 12 h had no obvious effect on parasite growth or gross morphology but induced hypoacetylation of histone H3 at K9 and K14, but not H4 at K5, K8, K12, and K16, suggesting inhibition of the PfGCN5 HAT. Microarray analysis showed that this AA treatment resulted in twofold or greater change in the expression of 271 (similar to 5%) parasite genes in late trophozoites, among which 207 genes were downregulated. Cluster analysis of gene expression indicated that AA mostly downregulated active genes, and this gene pool significantly overlapped with that enriched for H3K9 acetylation. We further demonstrated by chromatin immunoprecipitation and real-time PCR that AA treatment reduced acetylation near the putative promoters of a set of downregulated genes. This study suggests that the parasiticidal effect of AA is at least partially associated with its inhibition of PfGCN5 HAT, resulting in the disturbance of the transcription program in the parasites. C1 [Cui, Long; Miao, Jun; Fan, Qi; Li, Xinyi; Cui, Liwang] Penn State Univ, Dept Entomol, University Pk, PA 16802 USA. [Furuya, Tetsuya; Su, Xin-zhuan] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Rathod, Pradipsinh K.] Univ Washington, Dept Chem, Seattle, WA 98195 USA. RP Cui, LW (reprint author), Penn State Univ, Dept Entomol, 501 ASI Bldg, University Pk, PA 16802 USA. EM luc2@psu.edu RI Miao, Jun/F-5340-2010; li, xinyi/D-5403-2009; Furuya, Tetsuya/J-5916-2013; Furuya, Tetsuya/H-2412-2013; OI li, xinyi/0000-0001-8791-2931; Furuya, Tetsuya/0000-0003-3979-7072; Su, Xinzhuan/0000-0003-3246-3248 FU NIH [AI064553]; Division of Intramural Research; NIAID FX We are grateful to Bill Sullivan at Indiana University for critically reading the manuscript.; We thank the NIH for grant support (AI064553) to L.C. and the Division of Intramural Research, NIAID, NIH, for support to X.S. NR 57 TC 57 Z9 59 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 J9 EUKARYOT CELL JI Eukaryot. Cell PD JUL PY 2008 VL 7 IS 7 BP 1200 EP 1210 DI 10.1128/EC.00063-08 PG 11 WC Microbiology; Mycology SC Microbiology; Mycology GA 340SX UT WOS:000258666400013 PM 18487348 ER PT J AU de Silva, R Raval, AN Hadi, M Gildea, KM Bonifacino, AC Yu, ZX Yau, YY Leitman, SF Bacharach, SL Donahue, RE Read, EJ Lederman, RJ AF de Silva, Ranil Raval, Amish N. Hadi, Mohiuddin Gildea, Karena M. Bonifacino, Aylin C. Yu, Zu-Xi Yau, Yu Ying Leitman, Susan F. Bacharach, Stephen L. Donahue, Robert E. Read, Elizabeth J. Lederman, Robert J. TI Intracoronary infusion of autologous mononuclear cells from bone marrow or granulocyte colony-stimulating factor-mobilized apheresis product may not improve remodelling, contractile function, perfusion, or infarct size in a swine model of large myocardial infarction SO EUROPEAN HEART JOURNAL LA English DT Article DE angiogenesis; imaging; myocardial infarction; myogenesis; stem cell ID RANDOMIZED CONTROLLED-TRIAL; PRIMARY ANGIOPLASTY; PROGENITOR CELLS; DOUBLE-BLIND; STEM-CELLS; REGENERATION; TRANSPLANTATION; INJECTION; ENHANCEMENT; VALIDATION AB Aims In a blinded, placebo-controlled study, we investigated whether intracoronary infusion of autologous mononuclear cells from granulocyte colony-stimulating factor (G-CSF)-mobilized apheresis product or bone marrow (BM) improved sensitive outcome measures in a swine model of large myocardial infarction (MI). Methods and results Four days after left anterior descending (LAD) occlusion and reperfusion, cells from BM or apheresis product of saline- (placebo) or G-CSF-injected animals were infused into the LAD. Large infarcts were created: baseline ejection fraction (EF) by magnetic resonance imaging (MRI) of 35.3 +/- 8.5%, no difference between the placebo, G-CSF, and BM groups (P = 0.16 by ANOVA). At 6 weeks, EF fell to a similar degree in the placebo, G-CSF, and BM groups (-7.9 +/- 6.0, -8.5 +/- 8.8, and -10.9 +/- 7.6%, P = 0.78 by ANOVA). Left ventricular volumes and infarct size by MRI deteriorated similarly in all three groups. Quantitative positron emission tomography (PET) demonstrated significant decline in fluorodeoxyglucose uptake rate in the LAD territory at follow-up, with no histological, angiographic, or PET perfusion evidence of functional neovascularization. Immunofluorescence failed to demonstrate transdifferentiation of infused cells. Conclusions Intracoronary infusion of mononuclear cells from either BM or G-CSF-mobilized apheresis product may not improve or limit deterioration in systolic function, adverse ventricular remodelling, infarct size, or perfusion in a swine model of large MI. C1 [Hadi, Mohiuddin; Bacharach, Stephen L.] NIH, Dept Nucl Med, Bethesda, MD 20892 USA. [de Silva, Ranil; Raval, Amish N.; Gildea, Karena M.; Lederman, Robert J.] NHLBI, Cardiol Branch, Div Intramural Res, Bethesda, MD 20892 USA. [Bonifacino, Aylin C.; Donahue, Robert E.] NHLBI, Div Intramural Res, Haematol Branch, Bethesda, MD 20892 USA. [Yau, Yu Ying; Leitman, Susan F.; Read, Elizabeth J.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA. RP de Silva, R (reprint author), Royal Brompton & Harefield NHS Trust, Imperial Coll London, NHLI, Sydney St, London SW3 6NP, England. EM r.desilva@imperial.ac.uk RI Hadi, Mohiuddin/H-5682-2012 FU Intramural NIH HHS [Z01 HL005062-05]; NHLBI NIH HHS [Z01 HL005062, Z01-HL005062-04] NR 30 TC 21 Z9 21 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD JUL PY 2008 VL 29 IS 14 BP 1772 EP 1782 DI 10.1093/eurheartj/ehn216 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 328HB UT WOS:000257787900015 PM 18502738 ER PT J AU Staal, FJT Sen, JM AF Staal, Frank J. T. Sen, Jyoti M. TI The canonical Wnt signaling pathway plays an important role in lymphopoiesis and hematopoiesis SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Review DE development; stem cell; thymus; Wnt signaling ID BETA-CATENIN EXPRESSION; TRANSCRIPTION FACTOR LEF-1; STEM-CELL REPOPULATION; THYMOCYTE SURVIVAL; IN-VIVO; LYMPHOCYTE DEVELOPMENT; THYMIC DEVELOPMENT; GENE-EXPRESSION; GAMMA-CATENIN; DIFFERENTIATION AB The evolutionarily conserved canonical Wnt-p-catenin-T cell factor (TCF)/Iymphocyte enhancer binding factor (LEF) signaling pathway regulates key checkpoints in the development of various tissues. Therefore, it is not surprising that a large body of gain-of-function and loss-of-function studies implicate Wnt-beta-catenin signaling in lymphopoiesis and hematopoiesis. In contrast, recent papers have reported that Mx-Cre-mediated conditional deletion of beta-catenin and/or its homolog gamma-catenin (plakoglobin) did not impair hernatopoiesis or lymphopoiesis. However, these studies also report that TCF reporter activity remains active in beta-catenin- and gamma-catenin-deficient hernatopoietic stem cells and all cells derived from these precursors, indicating that the canonical Wnt signaling pathway was not abrogated. Therefore, these studies in fact show that the canonical Wnt signaling pathway is important in hernatopoiesis and lymphopoiesis, even though the molecular basis for the induction of the reporter activity is currently unknown. In this perspective, we provide a broad background to the field with a discussion of the available data and create a framework within which the available and future studies may be evaluated. C1 [Staal, Frank J. T.] Erasmus Univ, Med Ctr, Dept Immunol, Rotterdam, Netherlands. [Sen, Jyoti M.] NIA, Lymphocyte Dev Unit, Immunol Lab, NIH, Baltimore, MD 21224 USA. RP Staal, FJT (reprint author), Erasmus Univ, Med Ctr, Dept Immunol, Rotterdam, Netherlands. EM f.staal@erasmusmc.nl FU Intramural NIH HHS [Z01 AG000768-04] NR 62 TC 65 Z9 68 U1 1 U2 6 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 JUL PY 2008 VL 38 IS 7 BP 1788 EP 1794 DI 10.1002/eji.200738118 PG 7 WC Immunology SC Immunology GA 328VM UT WOS:000257826300001 PM 18581335 ER PT J AU Huter, EN Punkosdy, GA Glass, DD Cheng, LI Ward, JM Shevach, EM AF Huter, Eva N. Punkosdy, George A. Glass, Deborah D. Cheng, Lily I. Ward, Jerrold M. Shevach, Ethan M. TI TGF-p-induced Foxp3(+) regulatory T cells rescue scurfy mice SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE autoimmune disease; regulatory T cells; scurfy mice; TGF-beta ID BETA; AUTOIMMUNITY; ENTEROPATHY; MOUSE AB Scurfy mice have a deletion in the forkhead domain of the forkhead transcription factor p3 (Foxp3), fail to develop thymic-derived, naturally occurring Foxp3(+) regulatory T cells (nTreg), and develop a fatal lymphoproliferative syndrome with multi-organ inflammation. Transfer of thymic-derived Foxp3(+) nTreg into neonatal Scurfy mice prevents the development of disease. Stimulation of conventional CD4(+)Foxp3(-) via the TCR in the presence of TGF-beta and IL-2 induces the expression of Foxp3 and an anergic/suppressive phenotype. To determine whether the TGF-beta-induced Treg (iTreg) were capable of suppressing disease in the Scurfy mouse, we reconstituted newborn Scurfy mice with polyclonal iTreg. Scurfy mice treated with iTreg do not show any signs of disease and have drastically reduced cell numbers in peripheral lymph nodes and spleen in comparison to untreated Scurfy controls. The iTreg retained their expression of Foxp3 in vivo for 21 days, migrated into the skin, and prevented the development of inflammation in skin, liver and lung. Thus, TGF-beta-differentiated Foxp3(+) Treg appear to possess all of the functional properties of thymic-derived nTreg and represent a potent population for the cellular immunotherapy of autoimmune and inflammatory diseases. C1 [Huter, Eva N.; Punkosdy, George A.; Glass, Deborah D.; Shevach, Ethan M.] NIAID, Immunol Lab, Cellular Immunol Sect, NIH, Bethesda, MD 20892 USA. [Cheng, Lily I.; Ward, Jerrold M.] NIAID, Infect Dis Pathogenesis Sect, Comparat Med Branch, NIH, Bethesda, MD 20892 USA. RP Huter, EN (reprint author), NIAID, Immunol Lab, Cellular Immunol Sect, NIH, Bldg 10,Room 11N315, Bethesda, MD 20892 USA. EM eshevach@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000224-26, Z01 AI000959-02] NR 19 TC 78 Z9 84 U1 1 U2 5 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 JUL PY 2008 VL 38 IS 7 BP 1814 EP 1821 DI 10.1002/eji.200838346 PG 8 WC Immunology SC Immunology GA 328VM UT WOS:000257826300006 PM 18546144 ER PT J AU Jin, YZ Thompson, BA Zhou, ZY Fu, Y Birnbaumer, L Wu, MX AF Jin, Yong Zhu Thompson, Brian A. Zhou, Zho Yan Fu, Yineng Birnbaumer, Lutz Wu, Mei X. TI Reciprocal function of G alpha i2 and G alpha i3 in graft-versus-host disease SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE G alpha i proteins; graft-versus-host disease; T cell trafficking ID HETEROTRIMERIC G-PROTEINS; T-CELLS; SPHINGOSINE 1-PHOSPHATE; MULTIGENE FAMILY; PERTUSSIS TOXIN; ALPHA-SUBUNIT; MICE; EXPRESSION; TRANSPLANTATION; LYMPHOCYTES AB This study delineates specific functions of G alpha i2 and G alpha i3 in T cell mobilization during the development of graft- versus-host disease (GVHD) and reveals reciprocal effects of these two G proteins on the onset and morbidity of the disease. A deletion of G alpha i2 hampered trafficking of pathogenic T cells from secondary lymphoid tissues to inflammatory sites and sufficiently prevented GVHD. In contrast, a severer disease was induced in mice adoptively transferred with G alpha i3-deficient T cells than those mice transferred with wild-type T cells. in agreement with this, pathogenic G alpha i2(-/-) T cells displayed a defect in response to CXCL10, CXCL11, and CCL5, whereas lack of G alpha i3 augmented T effector cell chemotaxis induced by CXCL10 and CXCL11 and resulted in their preference of homing to the liver and colon. Absence of either Gai also abrogated sphingosince-i-phosphate (SlP)-mediated inhibition of T cell chemokinesis and facilitated T cell homing and expansion in the spleen and mesenteric lymph nodes at the early phase of GVHD development, which is another key determinant in the severity and early onset of the disease in the mice infused with G alpha i3-T cells. These observations underscore interplay between G alpha i2 and G alpha i3 and potentially provide a novel strategy to prevent GVHD by blocking T cell homing at early stages and T effector cell trafficking at later time points. C1 [Jin, Yong Zhu; Thompson, Brian A.; Zhou, Zho Yan; Wu, Mei X.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Fu, Yineng] Harvard Univ, Sch Med, Dept Pathol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Birnbaumer, Lutz] Natl Inst Environm Hlth Sci, Transmembrane Signaling Grp, Lab Signal Transduct, Res Triangle Pk, NC USA. [Wu, Mei X.] Harvard MIT Div Hlth Sci & Technol, Boston, MA USA. RP Wu, MX (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Edwards 222,50 Blossom St, Boston, MA 02114 USA. EM mwu2@partners.org FU NIAID NIH HHS [R01 AI050822-05, K02 AI070785, R01 AI050822, AI 050822, K02 AI070785-02, AI 070785]; NIAMS NIH HHS [T32 AR007098, T32 AR 07098-31] NR 37 TC 6 Z9 6 U1 0 U2 1 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 JUL PY 2008 VL 38 IS 7 BP 1988 EP 1998 DI 10.1002/eji.200737738 PG 11 WC Immunology SC Immunology GA 328VM UT WOS:000257826300023 PM 18521956 ER PT J AU Pchelina, SN Yakimovskii, AF Emelyanov, AK Ivanova, ON Schwarzman, AL Singleton, AB AF Pchelina, S. N. Yakimovskii, A. F. Emelyanov, A. K. Ivanova, O. N. Schwarzman, A. L. Singleton, A. B. TI Screening for LRRK2 mutations in patients with Parkinson's disease in Russia: identification of a novel LRRK2 variant SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Article DE LRRK2; mutation; Parkinson's disease ID G2019S; GENE AB Background and purpose: Mutations in LRRK2, encoding leucine-rich repeat kinase 2 (or Dardarin), cause autosomal dominant Parkinson's disease (AdPD) and are also found in sporadic PD (sPD). To investigate the frequency of LRRK2 mutations in a sample of Russian PD patients. Methods: We sequenced the complete coding region of LRRK2 in 65 patients with AdPD and in 30 patients with sPD. Furthermore, in 20 patients with AdPD and in 159 patients with sPD we screened several common LRRK2 mutations (G2019S, R1441C/G/H, I2012T and I2020T). Results: Five AdPD patients had the LRRK2 G2019S mutation (5.9%, 5/85). In addition, we discovered a novel LRRK2 variant V1613A in a family with a tremor dominant form of AdPD; this variant was not present in controls. We identified two patients with LRRK2 mutations in sPD: one with the G2019S mutation (0.5; 1/189) and another with the previously described R1441C mutation (0,5; 1/189). Conclusions: LRRK2 mutations are common amongst patients with PD in Russia. The results also show that the G2019S mutation is the most frequent. We identified one novel mutation in a functional region of LRRK2. C1 [Pchelina, S. N.; Yakimovskii, A. F.; Ivanova, O. N.] Pavlov State Med Univ St Petersburg, Dept Mol & Gene Technol, St Petersburg 197089, Russia. [Emelyanov, A. K.; Schwarzman, A. L.] RAS, Petersburg Nucl Phys Inst, St Petersburg, Russia. [Singleton, A. B.] NIA, NIH, Mol Genet Unit, Bethesda, MD 20892 USA. RP Pchelina, SN (reprint author), Pavlov State Med Univ St Petersburg, Dept Mol & Gene Technol, L Tolstogo Str 6-8, St Petersburg 197089, Russia. EM sopchelina@hotmail.com RI Singleton, Andrew/C-3010-2009 FU Intramural NIH HHS NR 16 TC 17 Z9 18 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD JUL PY 2008 VL 15 IS 7 BP 692 EP 696 DI 10.1111/j.1468-1331.2008.02149.x PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 311XV UT WOS:000256634600011 PM 18435766 ER PT J AU Hutchinson, MR Zhang, YN Brown, K Coats, BD Shridhar, M Sholar, PW Patel, SJ Crysdale, NY Harrison, JA Maier, SF Rice, KC Watkins, LR AF Hutchinson, Mark R. Zhang, Yingning Brown, Kimberley Coats, Benjamen D. Shridhar, Mitesh Sholar, Paige W. Patel, Sonica J. Crysdale, Nicole Y. Harrison, Jacqueline A. Maier, Steven F. Rice, Kenner C. Watkins, Linda R. TI Non-stereoselective reversal of neuropathic pain by naloxone and naltrexone: involvement of toll-like receptor 4 (TLR4) SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE (+)-naloxone; (+)-naltrexone; microglia; stereoselectivity ID HIV-1 ENVELOPE GLYCOPROTEIN; MECHANICAL ALLODYNIA; SPINAL-CORD; PROINFLAMMATORY CYTOKINES; PERIPHERAL NEUROPATHY; OPIOIDERGIC SYSTEMS; TACTILE ALLODYNIA; RAT MODEL; ACTIVATION; GLIA AB Although activated spinal cord glia contribute importantly to neuropathic pain, how nerve injury activates glia remains controversial. It has recently been proposed, on the basis of genetic approaches, that toll-like receptor 4 (TLR4) may be a key receptor for initiating microglial activation following L5 spinal nerve injury. The present studies extend this idea pharmacologically by showing that TLR4 is key for maintaining neuropathic pain following sciatic nerve chronic constriction injury (CCI). Established neuropathic pain was reversed by intrathecally delivered TLR4 receptor antagonists derived from lipopolysaccharide. Additionally, (+)-naltrexone, (+)-naloxone, and (-)-naloxone, which we show here to be TLR4 antagonists in vitro on both stably transfected HEK293-TLR4 and microglial cell lines, suppressed neuropathic pain with complete reversal upon chronic infusion. Immunohistochemical analyses of spinal cords following chronic infusion revealed suppression of CCI-induced microglial activation by (+)-naloxone and (-)-naloxone, paralleling reversal of neuropathic pain. Together, these CCI data support the conclusion that neuron-to-glia signaling through TLR4 is important not only for initiating neuropathic pain, as suggested previously, but also for maintaining established neuropathic pain. Furthermore, these studies suggest that the novel TLR4 antagonists (+)-naloxone and (-)-naloxone can each fully reverse established neuropathic pain upon multi-day administration. This finding with (+)-naloxone is of potential clinical relevance. This is because (+)-naloxone is an antagonist that is inactive at the (-)-opioid selective receptors on neurons that produce analgesia. Thus, these data suggest that (+)-opioid antagonists such as (+)-naloxone may be useful clinically to suppress glial activation, yet (-)-opioid agonists suppress pain. C1 [Hutchinson, Mark R.; Zhang, Yingning; Brown, Kimberley; Coats, Benjamen D.; Shridhar, Mitesh; Sholar, Paige W.; Patel, Sonica J.; Crysdale, Nicole Y.; Harrison, Jacqueline A.; Watkins, Linda R.] Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. [Hutchinson, Mark R.; Zhang, Yingning; Brown, Kimberley; Coats, Benjamen D.; Shridhar, Mitesh; Sholar, Paige W.; Patel, Sonica J.; Crysdale, Nicole Y.; Harrison, Jacqueline A.; Maier, Steven F.; Watkins, Linda R.] Univ Colorado, Ctr Neurosci, Boulder, CO 80309 USA. [Hutchinson, Mark R.] Univ Adelaide, Discipline Pharmacol, Sch Med Sci, Adelaide, SA, Australia. [Rice, Kenner C.] Natl Inst Drug Abuse, Chem Biol Res Branch, Rockville, MD USA. [Rice, Kenner C.] Natl Inst Alcohol Abuse & Alcoholism, Natl Inst Hlth, Rockville, MD USA. RP Watkins, LR (reprint author), Univ Colorado, Dept Psychol, Campus Box 345, Boulder, CO 80309 USA. EM Linda.watkins@colorado.edu RI Hutchinson, Mark/A-9672-2008; Hutchinson, Mark/G-4147-2014 OI Hutchinson, Mark/0000-0003-2154-5950 FU Intramural NIH HHS; NIDA NIH HHS [R01 DA017670, DA015642, DA017670, K02 DA015642, K02 DA015642-05, K05 DA024044, K05 DA024044-01A1, R01 DA017670-03S1, R01 DA017670-03S2, R01 DA017670-04, R01 DA023132, R01 DA023132-01A1, R01 DA023132-01A1S1]; NIDCR NIH HHS [DE017782, R01 DE017782, R01 DE017782-03] NR 36 TC 174 Z9 179 U1 1 U2 15 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 JUL PY 2008 VL 28 IS 1 BP 20 EP 29 DI 10.1111/j.1460-9568.2008.06321.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA 327FT UT WOS:000257715700003 PM 18662331 ER PT J AU Merali, Z Anisman, H James, JS Kent, P Schulkin, J AF Merali, Zul Anisman, Hymie James, Jonathan S. Kent, Pam Schulkin, Jay TI Effects of corticosterone on corticotrophin-releasing hormone and gastrin-releasing peptide release in response to an aversive stimulus in two regions of the forebrain (central nucleus of the amygdala and prefrontal cortex) SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE bombesin; glucocorticoids; microdialysis; rat ID MESSENGER-RNA EXPRESSION; BOMBESIN-LIKE PEPTIDES; C-FOS EXPRESSION; CONDITIONED FEAR; PARAVENTRICULAR NUCLEUS; RAT-BRAIN; GLUCOCORTICOID-RECEPTOR; ADRENAL RESPONSES; PYRAMIDAL NEURONS; STRESS RESPONSES AB Previous research has shown that chronic corticosterone treatment increases the expression of corticotrophin-releasing hormone (CRH) mRNA at the central nucleus of the amygdala (CeA). Like CRH, gastrin-releasing peptide (GRP) appears to be involved in mediation of the stress response and is released at the CeA during exposure to an acute stressor. Using in-vivo microdialysis, this study examined the effects of corticosterone treatment on the release of CRH and GRP in response to an airpuff challenge at two forebrain regions, the CeA and medial prefrontal cortex. Adrenally intact rats were treated with corticosterone by systemic implants over a 14-day period prior to microdialysis probe insertion. We found that, at both regions, the airpuff-induced CRH and GRP release were enhanced in the corticosterone pellet-implanted rats as compared with the release observed in the vehicle-implanted control rats. These findings suggest that chronic corticosterone exposure potentiates the stressor-elicited release of CRH and GRP. As cortisol dysregulation has frequently been reported in people with psychiatric conditions, such as anxiety disorders or depression, a better understanding of the glucocorticoid-mediating regulation of CRH and GRP may provide insight into the underlying neurochemical mechanisms involved in both adaptive fear-type responses and maladaptive responses leading to pathology. C1 [Merali, Zul; Anisman, Hymie] Univ Ottawa, Mental Hlth Res Inst, Ottawa, ON K1Z 7K4, Canada. [Merali, Zul; James, Jonathan S.; Kent, Pam] Univ Ottawa, Dept Psychol, Ottawa, ON K1Z 7K4, Canada. [Merali, Zul; James, Jonathan S.; Kent, Pam] Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON K1Z 7K4, Canada. [Anisman, Hymie] Carleton Univ, Inst Neurosci, Ottawa, ON K1S 5B6, Canada. [Schulkin, Jay] Georgetown Univ, Sch Med, Mol Neuroimaging Sect, Natl Inst Mental Hlth,Dept Physiol, Bethesda, MD USA. [Schulkin, Jay] Georgetown Univ, Sch Med, Mol Neuroimaging Sect, Natl Inst Mental Hlth,Dept Biophys & Neurosci, Bethesda, MD USA. RP Merali, Z (reprint author), Univ Ottawa, Mental Hlth Res Inst, 1145 Carling Ave,Room 5432,Res Tower, Ottawa, ON K1Z 7K4, Canada. EM merali@uottawa.ca NR 81 TC 20 Z9 20 U1 0 U2 3 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 JUL PY 2008 VL 28 IS 1 BP 165 EP 172 DI 10.1111/j.1460-9568.2008.06281.x PG 8 WC Neurosciences SC Neurosciences & Neurology GA 327FT UT WOS:000257715700016 PM 18662341 ER PT J AU Siber, A Dragar, M Parsegian, VA Podgornik, R AF Siber, A. Dragar, M. Parsegian, V. A. Podgornik, R. TI Packing nanomechanics of viral genomes SO EUROPEAN PHYSICAL JOURNAL E LA English DT Article ID DNA DOUBLE HELICES; HYDRATION FORCES; INTERMOLECULAR FORCES; EJECTION FORCES; CONDENSED DNA; BACTERIOPHAGE; ORGANIZATION; CAPSIDS; POLYELECTROLYTES; FLEXIBILITY AB We investigate the osmotic equilibrium between a bulk polyethylene glycol (PEG) solution and DNA tightly packed in a spherical capsid. We base our analysis on the equations of thermodynamic equilibrium in terms of osmotic pressure. The equality between external osmotic pressure of PEG and osmotic pressure of tightly packed DNA gives us the DNA encapsidation curves. In this way we directly connect the wealth of existing osmotic pressure data for DNA in the bulk with the DNA encapsidation curves within small viral capsids. Specific calculations are made for a monovalent salt, Na+ -DNA and a divalent salt, Mn2+ -DNA that have quite different DNA encapsidation behaviors. The main conclusion of our work is that bending energy of DNA is of minor importance regarding the encapsidated DNA length, but has a non-negligible influence on the density distribution of DNA within the capsid. C1 [Siber, A.] Inst Phys, Zagreb 10001, Croatia. [Dragar, M.; Podgornik, R.] Univ Ljubljana, Fac Math & Phys, Dept Phys, SI-1000 Ljubljana, Slovenia. [Siber, A.; Podgornik, R.] Jozef Stefan Inst, Dept Theoret Phys, SI-1000 Ljubljana, Slovenia. [Parsegian, V. A.; Podgornik, R.] NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RP Siber, A (reprint author), Inst Phys, POB 304, Zagreb 10001, Croatia. EM rudolf.podgornik@fmf.uni-lj.si RI Siber, Antonio/B-8881-2008; Podgornik, Rudolf/C-6209-2008 OI Siber, Antonio/0000-0003-1665-6541; Podgornik, Rudolf/0000-0002-3855-4637 FU Intramural NIH HHS [Z01 HD000241-10] NR 41 TC 15 Z9 15 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1292-8941 J9 EUR PHYS J E JI Eur. Phys. J. E PD JUL PY 2008 VL 26 IS 3 BP 317 EP 325 DI 10.1140/epje/i2008-10330-7 PG 9 WC Chemistry, Physical; Materials Science, Multidisciplinary; Physics, Applied; Polymer Science SC Chemistry; Materials Science; Physics; Polymer Science GA 314RI UT WOS:000256826100010 PM 18528632 ER PT J AU Vanselow, J Selimyan, R Furbass, R AF Vanselow, J. Selimyan, R. Fuerbass, R. TI DNA methylation of placenta-specific Cyp19 promoters of cattle and sheep SO EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES LA English DT Article DE DNA methylation; bisulfite; gene expression; cotyledon; caruncle; corpus luteum ID CYTOCHROME-P450 ENCODING GENE; PROSTAGLANDIN PRODUCTION; EPIGENETIC REGULATION; OVINE PARTURITION; ESTRONE SULFATE; EXPRESSION; AROMATASE; 5-AZACYTIDINE; PROGESTERONE; ESTRADIOL AB Locally produced estrogens are important paracrine regulators of placental growth and differentiation in cattle and sheep. The key enzyme of estrogen biosynthesis, aromatase cytochrome P450, is encoded by Cyp19. Transcription of this gene in fetal cotyledons is the first regulatory step of placental estrogen production. The aim of the present study was to comparatively investigate if epigenetic mechanisms as tissue- and differentiation-specific DNA methylation might be involved in the regulation of placental Cyp19 expression. Earlier investigations demonstrated that cattle and sheep use different promoters, P1.1 and P1.5 for placental Cyp19 expression, respectively. During the present investigation, methylation of individual CpG dinucleotides within these promoter regions was analyzed with bisulfite direct sequencing in placental and luteal tissue. Transcript abundance in sheep was determined with qPCR. Both promoters contain only few CpGs and can therefore be classified as "low CpG density regions". The average methylation levels of both promoter regions were significantly reduced in cotyledons compared to caruncles and corpus luteum of both species, which inversely coincides with high and low expression levels, respectively. It was evident however that even neighbouring CpGs can show very different, individual methylation levels. From the data we conclude that (1) Cyp19 promoters are differentially methylated in ovine and bovine placental tissues of foetal and maternal origin; (2) DNA methylation is suggestively involved in the regulation of Cyp19 expression; (3) the DNA methylation status on its own is not Sufficient for the selection of tissue-and species-specific Cyp19 promoters. C1 [Vanselow, J.; Fuerbass, R.] FBN, D-18196 Dummerstorf, Germany. [Selimyan, R.] NIA, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. RP Vanselow, J (reprint author), FBN, Wilhelm Stahl Allee 2, D-18196 Dummerstorf, Germany. EM vanselow@fbn-dummerstorf.de NR 36 TC 16 Z9 18 U1 0 U2 5 PU JOHANN AMBROSIUS BARTH VERLAG MEDIZINVERLAGE HEIDELBERG GMBH PI STUTTGART PA RUEDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0947-7349 J9 EXP CLIN ENDOCR DIAB JI Exp. Clin. Endocrinol. Diabet. PD JUL PY 2008 VL 116 IS 7 BP 437 EP 442 DI 10.1055/s-2008-1058083 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 342FK UT WOS:000258769800009 PM 18523913 ER PT J AU Liu, J Shi, JZ Yu, LM Goyer, RA Waalkes, MP AF Liu, Jie Shi, Jing-Zheng Yu, Li-Mei Goyer, Robert A. Waalkes, Michael P. TI Mercury in traditional medicines: Is cinnabar toxicologically similar to common mercurials? SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Review DE cinnabar; traditional medicines; elementary mercury; mercuric chloride; methylmercury; bioavailability; disposition; toxicology ID PUBLIC-HEALTH; HEAVY-METALS; MICE; SULFIDE; EXPOSURE; AUTOIMMUNITY; GLUTATHIONE; ABSORPTION; CHILDREN; RATS AB Mercury is a major toxic metal ranked top in the Toxic Substances List. Cinnabar, which contains mercury sulfide, has been used in Chinese traditional medicines for thousands of years as an ingredient in various remedies, and 40 cinnabar-containing traditional medicines are still used today. Little is known about toxicology profiles or toxicokinetics of cinnabar and cinnabar-containing traditional medicines, and the high mercury content in these Chinese medicines raises justifiably escalations of public concern. This minireview, by searching the available database of cinnabar and by comparing cinnabar with common mercurials, discusses differences in their bioavailability, disposition, and toxicity. The analysis showed that cinnabar is insoluble and poorly absorbed from the gastrointestinal tract. Absorbed mercury from cinnabar is mainly accumulated in the kidneys, resembling the disposition pattern of inorganic mercury. Heating cinnabar results in release of mercury vapor, which in turn can produce toxicity similar to inhalation of these vapors. The doses of cinnabar required to produce neurotoxicity are 1000 times higher than methyl mercury. Following long-term use of cinnabar, renal dysfunction may occur. Dimercaprol and succimer are effective chelation therapies for general mercury intoxication including cinnabar. Pharmacological studies of cinnabar suggest sedative and hypnotic effects, but the therapeutic basis of cinnabar is still not clear. In summary, cinnabar is chemically inert with a relatively low toxic potential when taken orally. In risk assessment, cinnabar is less toxic than many other forms of mercury, but the rationale for its inclusion in traditional Chinese medicines remains to be fully justified. C1 [Liu, Jie; Goyer, Robert A.; Waalkes, Michael P.] NIEHS, NCI, Inorgan Carcinogenesis Sect, Res Triangle Pk, NC 27709 USA. [Shi, Jing-Zheng] Guiyang Tradit Med Coll, Dept Pharmacol, Guiyang, Peoples R China. RP Liu, J (reprint author), NIEHS, NCI, Inorgan Carcinogenesis Sect, Mail Drop F0-09, Res Triangle Pk, NC 27709 USA. EM Liu6@niehs.nih.gov FU Intramural NIH HHS [Z01 BC005488-22] NR 47 TC 59 Z9 76 U1 4 U2 37 PU SOC EXPERIMENTAL BIOLOGY MEDICINE PI MAYWOOD PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA SN 1535-3702 J9 EXP BIOL MED JI Exp. Biol. Med. PD JUL PY 2008 VL 233 IS 7 BP 810 EP 817 DI 10.3181/0712-MR-336 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 319HK UT WOS:000257154500004 PM 18445765 ER PT J AU Reyes-Reyes, EM Akiyama, SK AF Reyes-Reyes, E. Merit Akiyama, Steven K. TI Cell-surface nucleolin is a signal transducing P-selectin binding protein for human colon carcinoma cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE P-selectin; cell-surface nucleolin; cell adhesion; signal transduction ID TUMOR-METASTASIS; GLYCOPROTEIN LIGANDS; ENDOTHELIAL-CELLS; MEDIATES ADHESION; GROWTH-FACTOR; CANCER-CELLS; LUNG-CANCER; FLUID-FLOW; IDENTIFICATION; PLATELETS AB We have previously shown that P-selectin binding to Colo-320 human colon carcinoma cells induces specific activation of the alpha(5)beta(1) integrin with a concomitant increase of cell adhesion and spreading on fibronectin substrates in a phosphatidylinositol 3-kinase (PI3-K) and p38 MAPK-dependent manner. Here, we identified by affinity chromatography and characterized nucleolin as a P-selectin receptor on Colo-320 cells. Nucleolin mAb D3 significantly decreases the Colo-320 cell adhesion to immobilized P-selectin-IgG-Fc. Moreover, nucleolin becomes clustered at the external side of the plasma membrane of living, intact cells when bound to cross-linked P-selectin-IgG-Fc chimeric protein. We have also found P-selectin binding to Colo-320 cells induces tyrosine phosphorylation specifically of cell-surface nucleolin and formation of a signaling complex containing cell-surface nucleolin, PI3-K and p38 MAPK. Using siRNA approaches, we have found that both P-selectin binding to Colo-320 cells and formation of the P-selectin-mediated p38 MAPK/PI3-K signaling complex require nucleolin expression. These results show that nucleolin (or a nucleolin-like protein) is a signaling receptor for P-selectin on Colo-320 cells and suggest a mechanism for linkage of nucleolin to P-selectin-induced signal transduction pathways that regulate the adhesion and the spreading of Colo-320 on fibronectin substrates. Published by Elsevier Inc. C1 [Reyes-Reyes, E. Merit; Akiyama, Steven K.] NIEHS, Mol Carcinogenesis Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP Akiyama, SK (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. EM akiyama@niehs.nih.gov FU Intramural NIH HHS [Z01 ES023025-10, Z99 ES999999] NR 59 TC 49 Z9 53 U1 0 U2 1 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUL 1 PY 2008 VL 314 IS 11-12 BP 2212 EP 2223 DI 10.1016/j.yexcr.2008.03.016 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 319XY UT WOS:000257199500005 PM 18504038 ER PT J AU Gonczi, M Telek, A Czifra, G Balogh, A Blumberg, PM Biro, T Csernoch, L AF Goenczi, Monika Telek, Andrea Czifra, Gabriella Balogh, Attila Blumberg, Peter M. Biro, Tamas Csernoch, Laszlo TI Altered calcium handling following the recombinant overexpression of protein kinase C isoforms in HaCaT cells SO EXPERIMENTAL DERMATOLOGY LA English DT Article DE intracellular calcium; keratinocytes; protein kinase C ID HUMAN EPIDERMAL-KERATINOCYTES; INTRACELLULAR FREE CALCIUM; HUMAN SKIN; DIFFERENTIATION; PROLIFERATION; RECEPTORS; EXPRESSION; ISOZYMES; ACTIVATION; APOPTOSIS AB Both changes in intracellular calcium concentration ([Ca(2+)](i)) and activation of certain protein kinase C (PKC) isoforms play a crucial role in keratinocyte functions. To better understand the interaction between these two signalling pathways we investigated the resting [Ca(2+)](i) and the extracellular ATP-induced changes in [Ca(2+)](i) on HaCaT cell clones overexpressing either the classical alpha or the beta PKC isoform. These PKC isoenzymes were previously shown to decrease (alpha) or increase (beta) cell proliferation and augment (alpha) or suppress (beta) cell differentiation. Keratinocyte clones with decreased proliferation rate were found to have unaltered resting [Ca(2+)](i), but responded with greater calcium transients to the application of 180 mu M of ATP. In contrast, clones with increased proliferation rate had elevated resting [Ca(2+)](i) and suppressed calcium responses to ATP. Calcium transients on PKC beta clones displayed a faster falling phase. Each clone had a distinct purinergic receptor expression pattern, some of which paralleled the altered proliferation rate and calcium handling. Keratinocytes overexpressing PKC beta revealed decreased P2X1 and increased P2Y1 receptor expression as compared with the control or PKC alpha clones. The expression level of P2X7 was significantly increased in keratinocytes overexpressing PKC alpha. On the other hand neither the P2X2 nor the P2Y2 expression was altered significantly in the cell types investigated. These data indicate that a modified proliferation and differentiation pattern is associated with altered calcium handling in keratinocytes. The observations also suggest that different PKC isoenzymes have different effects on the phosphatidyl-inositol signalling pathway. C1 [Goenczi, Monika; Czifra, Gabriella; Biro, Tamas; Csernoch, Laszlo] Univ Debrecen, Dept Physiol, H-4012 Debrecen, Hungary. [Telek, Andrea; Csernoch, Laszlo] Univ Debrecen, Hungarian Acad Sci, Cell Physiol Res Grp, Debrecen, Hungary. [Balogh, Attila] Univ Debrecen, Dept Dermatol, Debrecen, Hungary. [Blumberg, Peter M.] NCI, Bethesda, MD 20892 USA. RP Csernoch, L (reprint author), Univ Debrecen, Dept Physiol, POB 22, H-4012 Debrecen, Hungary. EM csl@phys.dote.hu OI Csernoch, Laszlo/0000-0002-2446-1456 NR 37 TC 8 Z9 8 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD JUL PY 2008 VL 17 IS 7 BP 584 EP 591 DI 10.1111/j.1600-0625.2007.00678.x PG 8 WC Dermatology SC Dermatology GA 308MZ UT WOS:000256396000004 PM 18177346 ER PT J AU Chen, JC Young, NS AF Chen, Jichun Young, Neal S. TI Enrichment of hematopoietic stem cells with slam and LSK markers for the detection of hematopoietic stem cell function in normal and Trp53 null mice SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT ISEH 37th Annual Scientific Meeting/6th International Neonatal Hematology and Immunology Meeting CY JUL 09-12, 2008 CL Boston, MA C1 [Chen, Jichun; Young, Neal S.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2008 VL 36 IS 7 SU 1 BP S79 EP S80 PG 2 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 322BF UT WOS:000257349500190 ER PT J AU Ertl, RP Chen, J Astle, CM Duffy, TM Harrison, DE AF Ertl, Robin P. Chen, Jichun Astle, Clinton M. Duffy, Theodore M. Harrison, David E. TI Strain differences in hematopoietic stem cell aging between balb/cbyj and C57BL/6J mice: Function, number and response to diet restriction SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT ISEH 37th Annual Scientific Meeting/6th International Neonatal Hematology and Immunology Meeting CY JUL 09-12, 2008 CL Boston, MA C1 [Ertl, Robin P.; Astle, Clinton M.; Duffy, Theodore M.; Harrison, David E.] Jackson Lab, Bar Harbor, ME 04609 USA. [Chen, Jichun] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2008 VL 36 IS 7 SU 1 BP S72 EP S73 PG 2 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 322BF UT WOS:000257349500173 ER PT J AU Heaton, TE Peranteau, WH Bauer, TR Zoltick, PW Hickstein, DD Flake, AW AF Heaton, Todd E. Peranteau, William H. Bauer, Thomas R. Zoltick, Philip W. Hickstein, Dennis D. Flake, Alan W. TI The use of postnatal minimal conditioning bone marrow transplantation to achieve high-level chimerism and donor specific tolerance after in utero hematopoietic cell transplantation in the canine model SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT ISEH 37th Annual Scientific Meeting/6th International Neonatal Hematology and Immunology Meeting CY JUL 09-12, 2008 CL Boston, MA C1 [Heaton, Todd E.; Peranteau, William H.; Zoltick, Philip W.; Flake, Alan W.] Childrens Hosp Philadelphia, Ctr Fetal Res, Philadelphia, PA 19104 USA. [Bauer, Thomas R.; Hickstein, Dennis D.] NCI, Bethesda, MD 20892 USA. RI Heaton, Todd/E-5197-2016 OI Heaton, Todd/0000-0003-3515-0028 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2008 VL 36 IS 7 SU 1 BP S65 EP S65 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 322BF UT WOS:000257349500154 ER PT J AU Yaari, R Kumar, S Tariot, PN AF Yaari, Roy Kumar, Shubha Tariot, Pierre N. TI Non-cholinergic drug development for Alzheimer's disease SO EXPERT OPINION ON DRUG DISCOVERY LA English DT Review DE Alzheimer's; Alzheimer's disease; amyloid; AMPA; antiamyloid therapy; antidementia therapy; beta-secretase; beta-secretase inhibitor; dementia; dimebon; drug development; gamma-secretase; gamma-secretase inhibitor; glutamate; immunization; immunotherapy; NMDA; SALA; secretase inhibitor; selective A beta-lowering agent; tangle; tau ID AMYLOID-BETA-PEPTIDE; CENTRAL-NERVOUS-SYSTEM; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; MILD COGNITIVE IMPAIRMENT; GAMMA-SECRETASE INHIBITOR; REVERSIBLE MEMORY LOSS; GINKGO-BILOBA EXTRACT; PRECURSOR PROTEIN APP; N-3 FATTY-ACIDS; TRANSGENIC MICE AB Background: Recent advances in the understanding of the pathobiology of Alzheimer's disease have led to a large number of non-cholinergic targets for the development of therapeutic agents. These include, for example, neurotransmitter-based, anti-amyloid, antitangle, antioxidant, anti-excitotoxic, and growth factor strategies. There are several hundred agents in, or approaching, clinical trials. Some hold promise for treatment of those affected, some may have potential for prevention, some for both. Objectives: Key examples of each of these development approaches will be summarized. Conclusions: it is too soon to predict which, if any, of these approaches will bear fruit. At the moment, it appears that the amyloid-based therapies are the farthest along in development, and have shown in some cases that the amyloid dysregulation cascade can be interrupted. it is unknown, however, whether altering this aspect of the pathobiology of Alzheimer's will actually yield clinical benefit. Efforts to affect tangle development would appear to be a fruitful approach, although these efforts lag behind the anti-amyloid efforts. The same is essentially true for the other approaches reviewed as well. Given the fact that many new interventions target specific pathways that can be measured biologically in go-no go proof of concept studies, the opportunity exists to capitalize on biomarkers in earlier stages of development. The same can be said for evolving imaging techniques. Given the number of agents in development, we offer the provocative suggestion that the biggest threat to identifying effective therapies may prove to be the implementation of enough treatment trials, and applying out-of-the-box prevention methodologies, rather than the discovery of promising candidates. This prediction may or may not hold true. C1 [Yaari, Roy; Kumar, Shubha; Tariot, Pierre N.] Banner Alzheimers Inst, Phoenix, AZ 85006 USA. [Tariot, Pierre N.] Univ Arizona, Coll Med, Dept Psychiat, Phoenix, AZ USA. [Tariot, Pierre N.] Natl Inst Ageing U01 AG10483, Phoenix, AZ USA. [Tariot, Pierre N.] Mental Hlth Res Inst, Phoenix, AZ USA. RP Yaari, R (reprint author), Banner Alzheimers Inst, 901 E Willetta St, Phoenix, AZ 85006 USA. EM Roy.yaari@bannerhealth.com FU Abbott Laboratories; GlaxoSmithKJine; Medivation; Merck and Company; Merz; Pfizer Inc.; Takeda Pharmaceuticals North America Inc.; Wyeth Laboratories; Elan; NIA; NIMH; Alzheimer's Association; Arizona Department of Health Services; Institute for Mental Health Research FX In the past 2 years, PN Tariot has received consulting fees from AC Immune, AstraZeneca, Avid, Baxter Heakhcare Corp., Eisai Inc., Epix Pharmaceuticals, Forest Laboratories, Memory Pharmaceuticals Inc., Myriad Pharmaceuticals, Sanofi-Aventis and Toyama; he received consulting fees and research support from Abbott Laboratories, GlaxoSmithKJine, Medivation, Merck and Company, Merz, Pfizer Inc., Takeda Pharmaceuticals North America Inc., and Wyeth Laboratories; he also received educational fees from Lundbeck, research support from Elan, as well as other research support from NIA, NIMH, Alzheimer's Association, Arizona Department of Health Services, and the Institute for Mental Health Research. In addition he is listed as a contributor to a patent 'Biomarkers for Alzheimer's Disease'. R Yaari has received consulting fees from Merck and Company. NR 126 TC 4 Z9 4 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1746-0441 J9 EXPERT OPIN DRUG DIS JI Expert. Opin. Drug Discov. PD JUL PY 2008 VL 3 IS 7 BP 745 EP 760 DI 10.1517/17460440802190476 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 362CP UT WOS:000260176100005 PM 23496218 ER PT J AU Ma, XC Idle, JR Gonzalez, FJ AF Ma, Xiaochao Idle, Jeffrey R. Gonzalez, Frank J. TI The pregnane X receptor: from bench to bedside SO EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY LA English DT Review DE clinical implications; nuclear receptor; pregnane X receptor; PXR-humanized mouse; Pxr-null mouse ID INFLAMMATORY-BOWEL-DISEASE; CONSTITUTIVE-ANDROSTANE RECEPTOR; PRIMARY BILIARY-CIRRHOSIS; DRUG-DRUG INTERACTIONS; HUMAN CYTOCHROME-P450 3A4; CYP3A4 GENE-EXPRESSION; VITAMIN-D METABOLISM; SERUM BILE-ACIDS; NUCLEAR RECEPTOR; XENOBIOTIC RECEPTOR AB Background: The pregnane X receptor (PXR; NR1I2), a member of the nuclear receptor superfamily, regulates the expression of metabolic enzymes and transporters involved in the response of mammals to their chemical environment. Objective: To summarize the functions and clinical implications of PXR. Methods: In the current review, the clinical implications of PXR are discussed, and the use of genetically engineered PXR mouse models is highlighted. Results/conclusion: Recent advances in mouse models, including Pxr-null and PXR-humanized mice, provide in vivo tools for evaluating the physiological functions of PXR and its role in controlling xenobiotic metabolism and transport. By using the PXR knockout and humanized mouse models, PXR was found to influence drug-drug interactions, hepatic steatosis, and the homeostasis of vitamin D, bile acids, and steroid hormones. PXR was also shown to influence inflammatory bowel diseases. C1 [Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA. [Idle, Jeffrey R.] Charles Univ Prague, Inst Pharmacol, Fac Med 1, Prague 12800 2, Czech Republic. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, Bldg 37,Room 3106, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov OI Idle, Jeff/0000-0002-6143-1520 FU Intramural NIH HHS [Z01 BC005562-20] NR 111 TC 63 Z9 65 U1 0 U2 8 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1742-5255 J9 EXPERT OPIN DRUG MET JI Expert Opin. Drug Metab. Toxicol. PD JUL PY 2008 VL 4 IS 7 BP 895 EP 908 DI 10.1517/17425250802176134 PG 14 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 334VO UT WOS:000258249600005 PM 18624678 ER PT J AU Huang, MC Liao, JJ Bonasera, S Longo, DL Goetzl, EJ AF Huang, Mei-Chuan Liao, Jia-Jun Bonasera, Stephen Longo, Dan L. Goetzl, Edward J. TI Nuclear factor-kappa B-dependent reversal of aging-induced alterations in T cell cytokines SO FASEB JOURNAL LA English DT Article DE immunosenescence; inflammation; autoimmunity; phytochemicals ID IMMUNE RISK PHENOTYPE; SPHINGOSINE 1-PHOSPHATE; CUTTING EDGE; AGED MICE; LATE-LIFE; LYMPHOCYTES; ACTIVATION; INTERLEUKIN-18; INFLAMMATION; INHIBITION AB Immunosenescence is characterized by decreases in protective immune responses and increases in inflammation and autoimmunity. The T helper (Th) 17 subset of cluster-of-differentiation (CD) 4 T cells, which is identified by its generation of interleukin (IL)-17, is implicated in autoimmune pathogenesis. To elucidate immunosenescent changes in Th17 cell cytokines, splenic CD4 T cells from 22-to 24-month-old (old) mice and 6-to 10-wk-old (young) mice were incubated on anti-CD3 plus anti-CD28 (anti-T cell antigen receptor) antibodies. After 96 h, T cells of old C57BL/6 and CBA mice generated up to 20-fold more IL-17 and up to 3-fold more IL-6 than those of young mice; T cells of young mice generated up to 5-fold more IL-21 than those of old mice; and no difference was found for IFN-gamma. At 24 h, cytokine mRNA levels paralleled 96 h cytokine concentrations. Naive CD4 T cells from old mice incubated on anti-T cell antigen receptor antibodies with transforming growth factor-beta, IL-1, IL-6, and IL-23 to induce de novo differentiation of Th17 cells had more IL-17 mRNA and produced more IL-17 than those of young mice. BAY11-7082 and the phytochemicals triptolide and butein suppressed nuclear concentrations of nuclear factor-kappa B and secreted levels of IL-17, IL-21, and IFN-gamma in parallel, with greater potency in Th17 cells from young than old mice. Pharmacological correction of altered generation of Th17 cell cytokines in immunosenescence represents a novel therapeutic approach to aging-induced inflammatory diseases. C1 [Huang, Mei-Chuan; Liao, Jia-Jun; Bonasera, Stephen; Goetzl, Edward J.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Longo, Dan L.] NIA, NIH, Baltimore, MD 21224 USA. RP Goetzl, EJ (reprint author), Univ Calif San Francisco, Dept Med, Room UB8B,533 Parnassus 4th Ave, San Francisco, CA 94143 USA. EM edward.goetzl@ucsf.edu FU Intramural NIH HHS; NHLBI NIH HHS [R0-1 HL31809]; NIA NIH HHS [R21 AG026043] NR 38 TC 37 Z9 41 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL PY 2008 VL 22 IS 7 BP 2142 EP 2150 DI 10.1096/fj.07-103721 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 321GK UT WOS:000257292500006 PM 18267981 ER PT J AU Chen, SY Pan, CJ Nandigama, K Mansfield, BC Ambudkar, SV Chou, JY AF Chen, Shih-Yin Pan, Chi-Jiunn Nandigama, Krishnamachary Mansfield, Brian C. Ambudkar, Suresh V. Chou, Janice Y. TI The glucose-6-phosphate transporter is a phosphate-linked antiporter deficient in glycogen storage disease type Ib and Ic SO FASEB JOURNAL LA English DT Article DE proteoliposomes; glucose-6-phosphatase-alpha; endoplasmic reticulum; chorogenic acid; vanadate ID ESCHERICHIA-COLI; MICROSOMAL GLUCOSE-6-PHOSPHATASE; GLUCOSE 6-PHOSPHATASE; TRANSMEMBRANE TOPOLOGY; ENZYME-DEFICIENT; CHROMOSOME 11Q23; ANION-EXCHANGE; NON-A; GENE; MUTATIONS AB Glycogen storage disease type Ib (GSD-Ib) is caused by deficiencies in the glucose-6-phosphate (G6P) transporter (G6PT) that have been well characterized. Interestingly, deleterious mutations in the G6PT gene were identified in clinical cases of GSD type Ic (GSD-Ic) proposed to be deficient in an inorganic phosphate (P-i) transporter. We hypothesized that G6PT is both the G6P and Pi transporter. Using reconstituted proteoliposomes we show that both G6P and P-i are efficiently taken up into P-i-loaded G6PT-proteoliposomes. The G6P uptake activity decreases as the internal: external P-i ratio decreases and the P-i uptake activity decreases in the presence of external G6P. Moreover, G6P or P-i uptake activity is not detectable in P-i-loaded proteoliposomes containing the p.R28H G6PT null mutant. The G6PT-proteoliposome-mediated G6P or P-i uptake is inhibited by cholorgenic acid and vanadate, both specific G6PT inhibitors. Glucose-6-phosphatase-alpha (G6Pase-alpha), which facilitates microsomal G6P uptake by G6PT, fails to stimulate G6P uptake in P-i-loaded G6PT-proteoliposomes, suggesting that the G6Pase-alpha-mediated stimulation is caused by decreasing G6P and increasing P-i concentrations in microsomes. Taken together, our results suggest that G6PT has a dual role as a G6P and a P-i transporter and that GSD-Ib and GSD-Ic are deficient in the same G6PT gene. C1 [Chen, Shih-Yin; Pan, Chi-Jiunn; Mansfield, Brian C.; Chou, Janice Y.] NICHHD, Sect Cellular Differentiat, Heritable Disorders Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. [Nandigama, Krishnamachary; Ambudkar, Suresh V.] Natl Canc Inst, Cell Biol Lab, Ctr Canc Res, Natl Inst Hlth, Bethesda, MD USA. RP Chou, JY (reprint author), NICHHD, Sect Cellular Differentiat, Heritable Disorders Branch, Natl Inst Hlth, Bldg 10,Rm 9D42,10 Ctr Dr, Bethesda, MD 20892 USA. EM chouja@mail.nih.gov OI Mansfield, Brian/0000-0002-8533-2789 FU Intramural NIH HHS NR 46 TC 27 Z9 28 U1 2 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL PY 2008 VL 22 IS 7 BP 2206 EP 2213 DI 10.1096/fj.07-104851 PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 321GK UT WOS:000257292500013 PM 18337460 ER PT J AU Bjork, K Rimondini, R Hansson, AC Terasmaa, A Hyytia, P Heilig, M Sommer, WH AF Bjork, K. Rimondini, R. Hansson, A. C. Terasmaa, A. Hyytia, P. Heilig, M. Sommer, W. H. TI Modulation of voluntary ethanol consumption by beta-arrestin 2 SO FASEB JOURNAL LA English DT Article DE alcoholism; animal model; brain; gene expression; ethanol preference ID RECEPTOR KNOCKOUT MICE; C-FOS EXPRESSION; NUCLEUS-ACCUMBENS; ALCOHOL-DRINKING; ANTISENSE OLIGONUCLEOTIDE; MORPHINE ANALGESIA; NERVOUS-SYSTEM; DRUG-ADDICTION; ANIMAL-MODELS; RAT AB Beta-arrestin 2 is a multifunctional key component of the G protein-coupled receptor complex and is involved in mu-opiate and dopamine D2 receptor signaling, both of which are thought to mediate the rewarding effects of ethanol consumption. We identified elevated expression of the beta-arrestin 2 gene (Arrb2) in the striatum and the hippocampus of ethanol-preferring AA rats compared to their nonpreferring counterpart ANA line. Differential mRNA expression was accompanied by different levels of Arrb2 protein. The elevated expression was associated with a 7-marker haplotype in complete linkage disequilibrium, which segregated fully between the lines, and was unique to the preferring line. Furthermore, a single, distinct, and highly significant quantitative trait locus for Arrb2 expression in hippocampus and striatum was identified at the locus of this gene, providing evidence that genetic variation may affect a cis-regulatory mechanism for expression and regional control of Arrb2. These findings were functionally validated using mice lacking Arrb2, which displayed both reduced voluntary ethanol consumption and ethanol-induced psychomotor stimulation. Our results demonstrate that beta-arrestin 2 modulates acute responses to ethanol and is an important mediator of ethanol reward. C1 [Bjork, K.; Hansson, A. C.; Terasmaa, A.; Heilig, M.; Sommer, W. H.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. [Bjork, K.; Rimondini, R.] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. [Hyytia, P.] Natl Publ Hlth Inst, Dept Mental Hlth & Alcohol Res, Helsinki, Finland. RP Sommer, WH (reprint author), NIAAA, Lab Clin & Translat Studies, NIH, 10 Ctr Dr,B 10,R 15330, Bethesda, MD 20892 USA. EM wolfgang.sommer@mail.nih.gov RI Rimondini, Roberto/B-2500-2010; Terasmaa, Anton/I-3312-2015; OI Rimondini, Roberto/0000-0003-4099-513X; Terasmaa, Anton/0000-0002-5139-1764; Hyytia, Petri/0000-0002-0284-1298 FU Intramural NIH HHS NR 54 TC 19 Z9 19 U1 0 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL PY 2008 VL 22 IS 7 BP 2552 EP 2560 DI 10.1096/fj.07-102442 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 321GK UT WOS:000257292500046 PM 18367649 ER PT J AU Vazquez-Padron, RI Pham, SM Mateu, D Khan, S Aitouche, A AF Vazquez-Padron, Roberto I. Pham, Si M. Mateu, Dania Khan, Sheik Aitouche, Abdelouahab TI An internal ribosome entry site mediates the initiation of soluble guanylyl cyclase beta 2 mRNA translation SO FEBS JOURNAL LA English DT Article DE IRES; nitric oxide; soluble guanylyl cyclase; translation; untranslated region ID NITRIC-OXIDE; 5'-UNTRANSLATED REGION; PROTEIN-SYNTHESIS; BETA(2) SUBUNIT; 2ND SUBUNIT; RAT-KIDNEY; EXPRESSION; IRES; PURIFICATION; CONTAINS AB The soluble guanylyl cyclases (sGC), the receptor for nitric oxide, are heterodimers consisting of an alpha- and beta-subunit. This study aimed to investigate the translational mechanism of the sGC beta 2-subunit. Two mRNA species for sGC beta 2 were isolated from human kidney. These transcripts had dissimilar 5'-untranslated regions (5'-UTRs). The most abundant sGC beta 2 mRNA showed numerous upstream open reading frames (ORFs) and stable secondary structures that inhibited in vivo and in vitro translation. To evaluate whether these 5'-UTRs harbored an internal ribosome entry site (IRES) that allows translation by an alternative mechanism, we inserted these regions between the two luciferase genes of a bicistronic vector. Transfection of those genetic constructs into HeLa cells demonstrated that both sGC beta 2 leaders had IRES activity in a cell-type dependent manner. Finally, the secondary structural model of the sGC beta 2 5'-UTR predicts a Y-type pseudoknot that characterizes the IRES of cellular mRNAs. In conclusion, our findings suggest that sGC beta 2 5'-UTRs have IRES activity that may permit sGC beta 2 expression under conditions that are not optimal for scanning-dependent translation. C1 [Vazquez-Padron, Roberto I.] Univ Miami, Miller Sch Med, Cardiothorac Surg & Vasc Biol Inst, Miami, FL 33136 USA. [Aitouche, Abdelouahab] NIH, Bethesda, MD 20892 USA. RP Vazquez-Padron, RI (reprint author), Univ Miami, Miller Sch Med, Cardiothorac Surg & Vasc Biol Inst, 1600 NW 10th Ave,RMSB 1063, Miami, FL 33136 USA. EM rvazquez@med.miami.edu FU NHLBI NIH HHS [R01 HL 63426] NR 35 TC 4 Z9 4 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 JUL PY 2008 VL 275 IS 14 BP 3598 EP 3607 DI 10.1111/j.1742-4658.2008.06505.x PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 327FV UT WOS:000257715900010 PM 18565106 ER PT J AU Ruopp, MD Collins, TC Whitcomb, BW Schisterman, EE AF Ruopp, Marcus D. Collins, Tara C. Whitcomb, Brian W. Schisterman, Enrique E. TI Evidence of absence or absence of evidence? A reanalysis of the effects of low-dose aspirin in in vitro fertilization SO FERTILITY AND STERILITY LA English DT Article DE aspirin; in vitro fertilization; pregnancy; implantation; fixed-effects ID INTRACYTOPLASMIC SPERM INJECTION; DOUBLE-BLIND; OVARIAN RESPONSIVENESS; STANDARD TREATMENT; PREGNANCY RATES; METAANALYSIS; IMPLANTATION; CONSUMPTION; PREVENTION; THERAPY AB Objective: To assess the conflicting evidence whether low-dose aspirin is beneficial in IVF and to evaluate the meta-analysis performed by Gelbaya et al. and reported in March 2007 in Human Reproduction Update, in which they found no effects of low-dose aspirin and recommended discontinuing its use in IVF. We present a reanalysis of the effects of low-dose aspirin in IVF and raise methodological questions regarding the analysis by Gelbaya et al. Design: A meta-analysis of prospective randomized trials evaluating the effects of low-dose aspirin in IVF. Patient(s): Women undergoing IVF/intracytoplasmic sperm injection. Intervention(S): Low-dose acetylsalicylic acid (aspirin). Main Outcome Measure(s): Pregnancy rates, implantation rates, miscarriage rates. Result(s): Ten randomized clinical trials were included in the analysis. Clinical pregnancy rate per ET was significant when low-dose aspirin was compared with no treatment (risk ratio 1.15, 95% confidence interval 1.03-1.27). Nonsignificant estimates comparing low-dose aspirin with no treatment were found for implantation and miscarriage rates. Conclusion(s): Our results suggest that aspirin may increase clinical pregnancy rates and that more data are needed to resolve the issue. At this point, there is no reason to change clinical management and discontinue the use of aspirin. C1 [Ruopp, Marcus D.; Collins, Tara C.; Whitcomb, Brian W.; Schisterman, Enrique E.] NICHHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, NIH, Bethesda, MD 20852 USA. RP Schisterman, EE (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, NIH, 6100 Execut Blvd, Bethesda, MD 20852 USA. EM schistee@mail.nih.gov OI Schisterman, Enrique/0000-0003-3757-641X FU Intramural NIH HHS [Z01 HD008795-01] NR 29 TC 25 Z9 26 U1 0 U2 2 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 JUL PY 2008 VL 90 IS 1 BP 71 EP 76 DI 10.1016/j.fertnstert.2007.06.033 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 326YM UT WOS:000257695600011 PM 17889863 ER PT J AU Feinberg, EC Levens, ED DeCherney, AH AF Feinberg, Eve C. Levens, Eric D. DeCherney, Alan H. TI Tubal reanastomosis or IVF? Reply of the authors SO FERTILITY AND STERILITY LA English DT Letter ID AGE C1 [Feinberg, Eve C.; Levens, Eric D.; DeCherney, Alan H.] NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. RP Feinberg, EC (reprint author), NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. NR 5 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 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JUL PY 2008 VL 90 IS 1 BP 243 EP 243 DI 10.1016/j.fertnstert.2008.05.008 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 326YM UT WOS:000257695600047 ER PT J AU Janssen-Heininger, YMW Mossman, BT Heintz, NH Forman, HJ Kalyanaraman, B Finkel, T Stamler, JS Rhee, SG van der Vliet, A AF Janssen-Heininger, Yvonne M. W. Mossman, Brooke T. Heintz, Nicholas H. Forman, Henry J. Kalyanaraman, Balaraman Finkel, Toren Stamler, Jonathan S. Rhee, Sue Goo van der Vliet, Albert TI Redox-based regulation of signal transduction: Principles, pitfalls, and promises SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Review DE oxidant; signal transduction; cysteine; S-glutathionylation; sulfenic acid; S-nitrosylation; peroxiredoxin; glutaredoxin; thioredoxin; biotin switch; free radicals ID PROTEIN-DISULFIDE-ISOMERASE; NF-KAPPA-B; NITRIC-OXIDE SYNTHASE; S-GLUTATHIONYLATED PROTEINS; TYROSINE-PHOSPHATASE 1B; CYSTEINE-SULFINIC ACID; ACTIVE-SITE CYSTEINE; SOLUBLE GUANYLYL CYCLASE; AIRWAY EPITHELIAL-CELLS; EPIDERMAL-GROWTH-FACTOR AB Oxidants are produced as a by-product of aerobic metabolism, and organisms ranging from prokaryotes to mammals have evolved with an elaborate and redundant complement of antioxidant defenses to confer protection against oxidative insults. Compelling data now exist demonstrating that oxidants are used in physiological settings as signaling molecules with important regulatory functions controlling cell division, migration, contraction, and mediator production. These physiological functions are carried out in an exquisitely regulated and compartmentalized manner by mild oxidants, through subtle oxidative events that involve targeted amino acids in proteins. The precise understanding of the physiological relevance of redox signal transduction has been hampered by the lack of specificity of reagents and the need for chemical derivatization to visualize reversible oxidations. In addition, it is difficult to measure these subtle oxidation events in vivo. This article reviews some of the recent findings that illuminate the significance of redox signaling and exciting future perspectives. We also attempt to highlight some of the current pitfalls and the approaches needed to advance this important area of biochemical and biomedical research. (C) 2008 Elsevier Inc. All rights reserved. C1 [Janssen-Heininger, Yvonne M. W.; Mossman, Brooke T.; Heintz, Nicholas H.; van der Vliet, Albert] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. [Forman, Henry J.] Univ Calif Merced, Sch Nat Sci, Merced, CA 95344 USA. [Kalyanaraman, Balaraman] Med Coll Wisconsin, Dept Biophys, Milwaukee, WI 53226 USA. [Finkel, Toren] NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. [Stamler, Jonathan S.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Rhee, Sue Goo] Ewha Womans Univ, Inst Mol Life Sci & Technol, Seoul, South Korea. RP Janssen-Heininger, YMW (reprint author), Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. EM yvonne.janssen@uvm.edu OI Forman, Henry Jay/0000-0001-5838-2791 FU NHLBI NIH HHS [R01 HL068865, P01 HL067004, P01HL67004, R01 HL060014, R01 HL060014-10, R01 HL074295, R01 HL079331, R01 HL079331-04, R01 HL085646, R01HL068865, R01HL074295, R01HL079331, R01HL60014]; NIEHS NIH HHS [R01 ES005511, R01ES05511] NR 243 TC 376 Z9 386 U1 8 U2 48 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 JUL 1 PY 2008 VL 45 IS 1 BP 1 EP 17 DI 10.1016/j.freeradbiomed.2008.03.011 PG 17 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 313CP UT WOS:000256719000001 PM 18423411 ER PT J AU Thomas, DD Ridnour, LA Isenberg, JS Flores-Santana, W Switzer, CH Donzelli, S Hussain, P Vecoli, C Paolocci, N Ambs, S Colton, CA Harris, CC Roberts, DD Wink, DA AF Thomas, Douglas D. Ridnour, Lisa A. Isenberg, Jeffrey S. Flores-Santana, Wilmarie Switzer, Christopher H. Donzelli, Sonia Hussain, Perwez Vecoli, Cecilia Paolocci, Nazareno Ambs, Stefan Colton, Carol A. Harris, Curtis C. Roberts, David D. Wink, David A. TI The chemical biology of nitric oxide: Implications in cellular signaling SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Review DE nitric oxide; oxidative; nitrosative; stress; free radicals ID CYTOCHROME-C-OXIDASE; MATRIX-METALLOPROTEINASE ACTIVITY; PROTEIN-TYROSINE NITRATION; HUMAN BREAST-CANCER; IN-VIVO; SUPEROXIDE GENERATION; ARGININE METABOLISM; NITROSATIVE STRESS; NMDA RECEPTOR; HEPATIC CYTOCHROME-P450 AB Nitric oxide (NO) has earned the reputation of being a signaling mediator with many diverse and often opposing biological activities. The diversity in response to this simple diatomic molecule comes from the enormous variety of chemical reactions and biological properties associated with it. In the past few years, the importance of steady-state NO concentrations has emerged as a key determinant of its biological function. Precise cellular responses are differentially regulated by specific NO concentration. We propose five basic distinct concentration levels of NO activity: cGMP-mediated processes ([NO] < 1-30 nM), Akt phosphorylation ([NO] = 30-100 nM), stabilization of HIF-1 alpha ([NO] = 100-300 nM), phosphorylation of p53 ([NO] > 400 nM), and nitrosative stress (1 mu M). In general, lower NO concentrations promote cell survival and proliferation, whereas higher levels favor cell cycle arrest, apoptosis, and senescence. Free radical interactions will also influence NO signaling. One of the consequences of reactive oxygen species generation is to reduce NO concentrations. This antagonizes the signaling of nitric oxide and in some cases results in converting a cell-cycle arrest profile to a cell survival profile. The resulting reactive nitrogen species that are generated from these reactions can also have biological effects and increase oxidative and nitrosative stress responses. A number of factors determine the formation of NO and its concentration, such as diffusion, consumption, and substrate availability, which are referred to as kinetic determinants for molecular target interactions. These are the chemical and biochemical parameters that shape cellular responses to NO. Herein we discuss signal transduction and the chemical biology of NO in terms of the direct and indirect reactions. Published by Elsevier Inc. C1 [Ridnour, Lisa A.; Flores-Santana, Wilmarie; Switzer, Christopher H.; Donzelli, Sonia; Wink, David A.] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. [Thomas, Douglas D.] Univ Illinois, Sch Pharm, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA. [Isenberg, Jeffrey S.; Roberts, David D.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Hussain, Perwez; Ambs, Stefan; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. [Vecoli, Cecilia; Paolocci, Nazareno] Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. [Colton, Carol A.] Duke Univ, Med Ctr, Div Neurol, Durham, NC 27710 USA. RP Wink, DA (reprint author), NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. EM wink@mail.nih.gov RI Roberts, David/A-9699-2008; Switzer, Christopher/D-9203-2013; ta, Inct/J-8374-2013; Vecoli, Cecilia/K-8613-2016; OI Roberts, David/0000-0002-2481-2981; Vecoli, Cecilia/0000-0002-5921-3604; Paolocci, Nazareno/0000-0001-7011-997X FU Intramural NIH HHS [Z01 BC010033-12]; NCI NIH HHS [K22 CA113315, K22 CA113315-01A2] NR 155 TC 352 Z9 369 U1 2 U2 48 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JUL 1 PY 2008 VL 45 IS 1 BP 18 EP 31 DI 10.1016/j.freeradbiomed.2008.03.020 PG 14 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 313CP UT WOS:000256719000002 PM 18439435 ER PT J AU Zhao, AP Urban, JF Anthony, RM Sun, R Stiltz, J Van Rooijen, N Wynn, TA Gause, WC Shea-Donohue, T AF Zhao, Aiping Urban, Joseph F., Jr. Anthony, Robert M. Sun, Rex Stiltz, Jennifer Van Rooijen, Nico Wynn, Thomas A. Gause, William C. Shea-Donohue, Terez TI Th2 cytokine-induced alterations in lntestinal smooth muscle function depend on alternatively activated macrophages SO GASTROENTEROLOGY LA English DT Article ID IMMUNE-RESPONSES; NIPPOSTRONGYLUS-BRASILIENSIS; INTESTINAL INFLAMMATION; HELMINTH INFECTION; CELLS; EXPRESSION; STAT6; IL-13; HYPERCONTRACTILITY; INTERLEUKIN-13 AB Background&Aim: Enteric nematode infection induces a strong type 2 T helper cell (Th2) cytokine response characterized by increased infiltration of various immune cells, including macrophages. The role of these immune cells in host defense against nematode infection remains poorly defined. The present study investigated the role of macrophages and the arginase pathway in nematode-induced changes in intestinal smooth muscle function and worm expulsion. Methods: Mice were infected with Nippostrongylus brasiliensis and treated with clodronate-containing liposome to deplete macrophages or given S-(2-boronoethyl)-I-cysteine in drinking water to inhibit arginase activity. Segments of intestinal smooth muscle were suspended in organ baths to determine responses to acetylcholine, 5-hydroxytryptamine, or nerve stimulation. The phenotype of macrophages was monitored by measuring mRNA expression of the specific molecular markers by real-time polymerase chain reaction or viewed by immunofluorescence staining. Resuits: Infection increased the infiltration of macrophages and up-regulation alternatively activated macrophage markers by a mechanism dependent on interleukin-4 (IL-4) or interleukin-13 (IL-13) activation of signal transducer and activator of transcription 6. Elimination of alternatively activated macrophages blocked smooth muscle hypercontractility and the increased smooth muscle thickness, and impaired worm expulsion. in addition, specific inhibition of arginase activity interfered with smooth muscle contractility, but only partially affected the protective immunity of the host. Conclusions: These data show that the phenotype of macrophages is determined by the local immune environment and that alternatively activated macrophages play a major role in the effects of Th2 cytokines, IL-4 and IL-13, on intestinal smooth muscle function. C1 [Zhao, Aiping; Sun, Rex; Stiltz, Jennifer; Shea-Donohue, Terez] Univ Maryland, Sch Med, Mucosal Biol Res Ctr, Baltimore, MD 21201 USA. [Zhao, Aiping; Sun, Rex; Stiltz, Jennifer; Shea-Donohue, Terez] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Urban, Joseph F., Jr.] Agr Res Serv, Diet Genom & Immunol Lab, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD USA. [Anthony, Robert M.; Gause, William C.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Med, Newark, NJ 07103 USA. [Van Rooijen, Nico] Vrije Univ Amsterdam, VUMC, Dept Mol & Cell Biol, Amsterdam, Netherlands. [Wynn, Thomas A.] NIAID, Div Parasitol, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Shea-Donohue, T (reprint author), Univ Maryland, Sch Med, Mucosal Biol Res Ctr, 20 Penn St, Baltimore, MD 21201 USA. EM tdonohue@mbrc.umaryland.edu RI Wynn, Thomas/C-2797-2011 FU NIAID NIH HHS [R01 AI031678-12, R01 AI031678, R01 AI031678-13, R01 AI031678-14, R01 AI049316, R01 AI049316-07, R01 AI049316-08, R01-AI/DK49316, R01-AI031678]; NIDDK NIH HHS [R01 DK049316, R01 DK083418, T32 DK067872] NR 30 TC 93 Z9 95 U1 3 U2 13 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 JUL PY 2008 VL 135 IS 1 BP 217 EP 225 DI 10.1053/j.gastro.2008.03.077 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 324XE UT WOS:000257551900029 PM 18471439 ER PT J AU Lucey, MM Wang, Y Bustin, M Duncan, MK AF Lucey, Michelle M. Wang, Yan Bustin, Michael Duncan, Melinda K. TI Differential expression of the HMGN family of chromatin proteins during ocular development SO GENE EXPRESSION PATTERNS LA English DT Article DE eye; lens; retina; cornea; chromatin ID NUCLEOSOMAL BINDING-PROTEIN; HIGH-MOBILITY; CELL FATE; CHROMOSOMAL-PROTEINS; GENE-EXPRESSION; DNA METHYLATION; XENOPUS-LAEVIS; MOUSE; LENS; ACTIVATION AB The HMGN proteins are a group of non-histone nuclear proteins that associate with the core nucleosome and alter the structure of the chromatin fiber. We investigated the distribution of the three best characterized HMGN family members, HMGN1, HMGN2 and HMGN3 during mouse eye development. HMGN1 protein is evenly distributed in all ocular structures of 10.5 days post-coitum (dpc) mouse embryos however, by 13.5 dpc, relatively less HMGN1 is detected in the newly formed lens fiber cells compared to other cell types. In the adult, HMGN1 is detected throughout the retina and lens, although in the cornea, HMGN1 protein is predominately located in the epithelium. HMGN2 is also abundant in all ocular structures of mouse embryos, however, unlike HMGN1, intense immunolabeling is maintained in the lens fiber cells at 13.5 dpc. in the adult eye, HMGN2 protein is still found in all lens nuclei while in the cornea, HMGN2 protein is mostly restricted to the epithelium. In contrast, the first detection of HMGN3 in the eye is in the presumptive corneal epithelium and lens fiber cells at 13.5 dpc. In the lens, HMGN3 remained lens fiber cell preferred into adulthood. In the cornea, HMGN3 is transiently upregulated in the stroma and endothelium at birth while its expression is restricted to the corneal epithelium in adulthood. In the retina, HMGN3 upregulates around 2 weeks of age and is found at relatively high levels in the inner nuclear and ganglion cell layers of the adult retina. RT-PCR analysis determined that the predominant HMGN3 splice form found in ocular tissues is HMGN3b which lacks the chromatin unfolding domain although HMGN3a mRNA is also detected. These results demonstrate that the HMGN class of chromatin proteins has a dynamic expression pattern in the developing eye. (C) 2008 Elsevier B.V. All rights reserved. C1 [Lucey, Michelle M.; Wang, Yan; Duncan, Melinda K.] Univ Delaware, Dept Biol Sci, Newark, DE 19716 USA. [Bustin, Michael] NCI, Prot Sect, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Duncan, MK (reprint author), Univ Delaware, Dept Biol Sci, 327 Wolf Hall, Newark, DE 19716 USA. EM duncanm@udel.edu RI Bustin, Michael/G-6155-2015; OI Duncan, Melinda/0000-0003-1570-322X FU Intramural NIH HHS [Z01 BC004496-30]; NCRR NIH HHS [P20 RR016472, P20 RR16472]; NEI NIH HHS [R01 EY012221-10, EY012221, R01 EY012221] NR 29 TC 7 Z9 8 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-133X J9 GENE EXPR PATTERNS JI Gene Expr. Patterns PD JUL PY 2008 VL 8 IS 6 BP 433 EP 437 DI 10.1016/j.gep.2008.04.002 PG 5 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 335TL UT WOS:000258313600010 PM 18502697 ER PT J AU Hai, M Adler, R Bauer, TR Tuschong, LM Gu, YC Wu, X Hickstein, DD AF Hai, M. Adler, R. L. Bauer, T. R., Jr. Tuschong, L. M. Gu, Y-C Wu, X. Hickstein, D. D. TI Potential genotoxicity from integration sites in CLAD dogs treated successfully with gammaretroviral vector-mediated gene therapy SO GENE THERAPY LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol DE hematopoietic stem cells; transplantation; retrovirus; LAM-PCR; integration site ID SCID-X1; LEUKEMIA; CELLS; VIVO; ADA AB Integration site analysis was performed on six dogs with canine leukocyte adhesion deficiency ( CLAD) that survived greater than 1 year after infusion of autologous CD34+ bone marrow cells transduced with a gammaretroviral vector expressing canine CD18. A total of 387 retroviral insertion sites (RIS) were identified in the peripheral blood leukocytes from the six dogs at 1 year postinfusion. A total of 129 RIS were identified in CD3+ T-lymphocytes and 102 RIS in neutrophils from two dogs at 3 years postinfusion. RIS occurred preferentially within 30 kb of transcription start sites, including 40 near oncogenes and 52 near genes active in hematopoietic stem cells. Integrations clustered around common insertion sites more frequently than random. Despite potential genotoxicity from RIS, to date there has been no progression to oligoclonal hematopoiesis and no evidence that vector integration sites influenced cell survival or proliferation. Continued follow-up in disease-specific animal models such as CLAD will be required to provide an accurate estimate of the genotoxicity using gammaretroviral vectors for hematopoietic stem cell gene therapy. C1 [Hai, M.; Adler, R. L.; Bauer, T. R., Jr.; Tuschong, L. M.; Gu, Y-C; Hickstein, D. D.] NCI, Expt Transplantat & Immunol Res, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Wu, X.] Natl Canc Inst Frederick, Lab Mol Technol, Sci Applicat Int Corp Frederick, Frederick, MD USA. RP Hickstein, DD (reprint author), NCI, Expt Transplantat & Immunol Res, Ctr Canc Res, NIH, 10 Ctr Dr,MSC1203,Bldg 10 CRC,Rm 3-3142, Bethesda, MD 20892 USA. EM hicksted@mail.nih.gov FU Intramural NIH HHS NR 15 TC 6 Z9 6 U1 0 U2 2 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 JUL PY 2008 VL 15 IS 14 BP 1067 EP 1071 DI 10.1038/gt.2008.52 PG 5 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 320YD UT WOS:000257270200006 PM 18369320 ER PT J AU Mosher, MJ Lange, LA Howard, BV Lee, ET Best, LG Fabsitz, RR MacCluer, JW North, KE AF Mosher, M. J. Lange, L. A. Howard, B. V. Lee, E. T. Best, L. G. Fabsitz, R. R. MacCluer, J. W. North, K. E. TI Sex-specific interaction between APOE genotype and carbohydrate intake affects plasma HDL-C levels: the strong heart family study SO GENES AND NUTRITION LA English DT Article DE APOE; carbohydrate; HDL-C; lipids; interaction ID APOLIPOPROTEIN-E POLYMORPHISM; HIGH-DENSITY-LIPOPROTEIN; REVERSE CHOLESTEROL TRANSPORT; BODY-MASS INDEX; CARDIOVASCULAR-DISEASE; AMERICAN-INDIANS; LIPID-METABOLISM; US ADULTS; RISK-FACTORS; NHANES-III AB Low plasma levels of high-density lipoprotein cholesterol (HDL-C) are identified as a risk factor for cardiovascular disease (CVD). Sexual dimorphism, however, is widely reported in both HDL-C and CVD, with the underlying explanations of these sexual differences not fully understood. HDL-C is a complex trait influenced by both genes and dietary factors. Here we examine evidence for a sex-specific effect of APOE and the macronutrient carbohydrate on HDL-C, triglycerides (TG) and apoprotein A-1 (ApoA-1) in a sample of 326 male and 423 female participants of the Strong Heart Family Study (SHFS). Using general estimating equations in SAS to account for kinship correlations, stratifying by sex, and adjusting for age, body mass index (BMI) and SHS center, we examine the relationship between APOE genotype and carbohydrate intake on circulating levels of HDL-C, TG, and ApoA-1 through a series of carbohydrate-by-sex interactions and stratified analyses. APOE-by-carbohydrate intake shows significant sex-specific effects. All males had similar decreases in HDL-C levels associated with increased carbohydrate intake. However, only those females with APOE-4 alleles showed significantly lower HDL-C levels as their percent of carbohydrate intake increased, while no association was noted between carbohydrate intake and HDL-C in those females without an APOE-4 allele. These findings demonstrate the importance of understanding sex differences in gene-by-nutrient interaction when examining the complex architecture of HDL-C variation. C1 [Mosher, M. J.] Univ Kansas, Lab Biol Anthropol, Lawrence, KS 66045 USA. [Mosher, M. J.] Western Washington Univ, Dept Anthropol, Bellingham, WA 98225 USA. [Best, L. G.] Missouri Breaks Ind Res Inc, Timber Lake, SD USA. [Fabsitz, R. R.] NHLBI, Epidemiol & Biometry Program, Bethesda, MD 20892 USA. [Lange, L. A.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Howard, B. V.] MedStar Res Inst, Washington, DC USA. [MacCluer, J. W.] SW Fdn Biomed Res, Dept Genet, San Antonio, TX USA. [Lee, E. T.] Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Ctr Amer Indian Hlth Res, Oklahoma City, OK USA. [North, K. E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [North, K. E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA. RP Mosher, MJ (reprint author), Univ Kansas, Lab Biol Anthropol, Lawrence, KS 66045 USA. EM mjmosher@email.unc.edu FU NHLBI [HL65520, HL 41642, HL41654, HL65521, T32-HL007055] FX We thank the Strong Heart Family Study participants. Without their participation, this project would not have been possible. In addition, the cooperation of the Indian Health Service hospitals and clinics and the directors of the SHS clinics, and the many collaborators and staff of the Strong Heart Study have made this project possible. Supported by NHLBI cooperative agreement that includes U01 grants HL65520, HL 41642, HL41654, and HL65521 and the Cardiovascular Training Grant, NHLBI, T32-HL007055. The views expressed in this paper are those of the authors and do not necessarily reflect those of the Indian Health Service. NR 81 TC 7 Z9 8 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1555-8932 J9 GENES NUTR JI Genes Nutr. PD JUL PY 2008 VL 3 IS 2 BP 87 EP 97 DI 10.1007/s12263-008-0075-4 PG 11 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA 353YF UT WOS:000259604600005 PM 18850190 ER PT J AU Gabrea, A Martelli, ML Qi, Y Roschke, A Barlogie, B Shaughnessy, JD Sawyer, JR Kuehl, WM AF Gabrea, Ana Martelli, Maria Luisa Qi, Ying Roschke, Anna Barlogie, Bart Shaughnessy, John D., Jr. Sawyer, Jeffrey R. Kuehl, W. Michael TI Secondary genomic rearrangements involving immunoglobulin or MYC loci show similar prevalences in hyperdiploid and nonhyperdiploid myeloma tumors SO GENES CHROMOSOMES & CANCER LA English DT Article ID MULTIPLE-MYELOMA; GENETIC ABNORMALITIES; TRANSLOCATIONS; DYSREGULATION; PATHWAY; 14Q32; EVENT; CELL AB The pathogenesis of multiple myeloma (MM) is thought to involve at least two pathways, which generate hyperdiploid (HRD) or nonhyperdiploid (NHRD) tumors, respectively. Apart from chromosome content, the two pathways are distinguished by five primary immunoglobulin heavy chain (IGH) rearrangements (4p16, FGFR3, and MMSET; 6p21, CCND3; 11q13, CCND1; 16q23, MAF; 20q12, MAFB) that are present mainly in NHRD tumors. To determine the prevalence and structures of IGH, immunoglobulin (IG) light chain, and MYC genomic rearrangements in MM, we have done comprehensive metaphase fluorescent in situ hybridization analyses on 48 advanced MM tumors and 47 MM cell lines. As expected, the prevalence of the five primary IGH rearrangements was nearly 70% in NHRD tumors, but only 12% in HRD tumors. However, IGH rearrangements not involving one of the five primary partners, and IG light chain rearrangements, have a similar prevalence in HRD and NHRD tumors. In addition, MYC rearrangements, which are thought to be late progression events that sometimes do not involve an IG heavy or light chain locus, also have a similar prevalence in HRD and NHRD tumors. In contrast to the primary IGH rearrangements, which usually are simple balanced translocations, these other IG rearrangements usually have complex structures, as previously described for MYC rearrangements in MM. We conclude that IG light chain and MYC rearrangements, as well as secondary IGH rearrangements, make similar contributions to the progression of both HRD and NHRD MM tumors. Published 2008 Wiley-Liss, Inc. C1 [Gabrea, Ana; Qi, Ying; Roschke, Anna; Kuehl, W. Michael] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Martelli, Maria Luisa] Univ Turin, Inst Canc Res & Treatment, Oncogenom Ctr, Turin, Italy. [Barlogie, Bart; Shaughnessy, John D., Jr.; Sawyer, Jeffrey R.] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Donna D & Donald M Lambert Lab Myeloma Genet, Little Rock, AR USA. RP Gabrea, A (reprint author), Bethesda Naval Hosp, Ctr Canc Res, NCI, NIH, 8901 Wisconsin Ave,Bldg 8,Room 5101, Bethesda, MD 20889 USA. EM anagabrea@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [CA97513, CA55819, R33 CA097513, P01 CA055819] NR 27 TC 44 Z9 44 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD JUL PY 2008 VL 47 IS 7 BP 573 EP 590 DI 10.1002/gcc.20563 PG 18 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 305JQ UT WOS:000256174800004 PM 18381641 ER PT J AU Kim, HH Abdelmohsen, K Lal, A Pullmann, R Yang, XL Galban, S Srikantan, S Martindale, JL Blethrow, J Shokat, KM Gorospe, M AF Kim, Hyeon Ho Abdelmohsen, Kotb Lal, Ashish Pullmann, Rudolf, Jr. Yang, Xiaoling Galban, Stefanie Srikantan, Subramanya Martindale, Jennifer L. Blethrow, Justin Shokat, Kevan M. Gorospe, Myriam TI Nuclear HuR accumulation through phosphorylation by Cdk1 SO GENES & DEVELOPMENT LA English DT Article DE RNA-binding protein; nucleocytoplasmic shuttling; 14-3-3 proteins; post-transcriptional gene regulation; cell division cycle; elav ID RNA-BINDING PROTEIN; MESSENGER-RNA; CYCLIN B1; STABILITY; AUF1; TRISTETRAPROLIN; TRANSLATION; INHIBITION; EXPRESSION; CLONING AB A predominantly nuclear RNA-binding protein, HuR translocates to the cytoplasm in response to stress and proliferative signals, where it stabilizes or modulates the translation of target mRNAs. Here, we present evidence that HuR phosphorylation at S202 by the G2-phase kinase Cdk1 influences its subcellular distribution. HuR was specifically phosphorylated in synchronous G2-phase cultures; its cytoplasmic levels increased by Cdk1-inhibitory interventions and declined in response to Cdk1-activating interventions. In keeping with the prominently cytoplasmic location of the nonphosphorylatable point mutant HuR(S202A), phospho-HuR(S202) was shown to be predominantly nuclear using a novel anti-phospho-HuR(S202) antibody. The enhanced cytoplasmic presence of unphosphorylated HuR was linked to its decreased association with 14-3-3 and to its heightened binding to target mRNAs. Our findings suggest that Cdk1 phosphorylates HuR during G2, thereby helping to retain it in the nucleus in association with 14-3-3 and hindering its post-transcriptional function and anti-apoptotic influence. C1 [Kim, Hyeon Ho; Abdelmohsen, Kotb; Lal, Ashish; Pullmann, Rudolf, Jr.; Yang, Xiaoling; Galban, Stefanie; Srikantan, Subramanya; Martindale, Jennifer L.; Gorospe, Myriam] NIA, Intramural Res Program, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. [Blethrow, Justin; Shokat, Kevan M.] Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA. RP Gorospe, M (reprint author), NIA, Intramural Res Program, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. EM myriam-gorospe@nih.gov OI srikantan, subramanya/0000-0003-1810-6519; abdelmohsen, Kotb/0000-0001-6240-5810 FU Intramural NIH HHS; NIBIB NIH HHS [EB001987, R01 EB001987] NR 52 TC 112 Z9 116 U1 0 U2 5 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 JUL 1 PY 2008 VL 22 IS 13 BP 1804 EP 1815 DI 10.1101/gad.1645808 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 320QD UT WOS:000257249200012 PM 18593881 ER PT J AU Jugessur, A Rahimov, F Lie, RT Wilcox, AJ Gjessing, HK Nilsen, RM Nguyen, TT Murray, JC AF Jugessur, Astanand Rahimov, Fedik Lie, Rolv T. Wilcox, Allen J. Gjessing, Hakon K. Nilsen, Roy M. Nguyen, Truc Trung Murray, Jeffrey C. TI Genetic variants in IRF6 and the risk of facial clefts: Single-marker and haplotype-based analyses in a population-based case-control study of facial clefts in Norway SO GENETIC EPIDEMIOLOGY LA English DT Article DE birth defects; facial clefts; genetic epidemiology; IRF6; case-control; case-parent triad; log-linear model; association analysis; haplotype analysis; haplotype relative risk; HAPLIN; HapMap ID POPLITEAL PTERYGIUM SYNDROMES; EXPRESSION ANALYSIS; PALATE; LIP; WOUDE; VAN; DISEQUILIBRIUM; ASSOCIATION; CONTRIBUTES AB Mutations in the gene encoding interferon regulatory factor 6 (IRF6) underlie a common form of syndromic clefting known as Van der Woude syndrome. Lip pits and missing teeth are the only additional features distinguishing the syndrome from isolated clefts. Van der Woude syndrome, therefore, provides an excellent model for studying the isolated forms of clefting. From a population-based case-control study of facial clefts in Norway (1996-2001), we selected 377 cleft lip with or without cleft palate (CL/P), 196 cleft palate only (CPO), and 763 control infant-parent triads for analysis. We genotyped six single nucleotide polymorphisms within the IRF6 locus and estimated the relative risks (RR) conferred on the child by alleles and haplotypes of the child and of the mother. On the whole, there were strong statistical associations with CL/P but not CPO in our data. In single-marker analyses, mothers with a double-dose of the W-allele at rs4844880 had an increased risk of having a child with CL/P (RR = 1.85, 95% confidence interval: 1.04-3.25; P = 0.036). An RR of 0.38 (95% confidence interval: 0.16-0.92; P = 0.031) was obtained when the child carried a single-dose of the W-allele at rs2235371 (the p.V274I polymorphism). The P-value for the overall test was <0.001. In haplotype analyses, several of the fetal and maternal haplotype relative risks were statistically significant individually but were not strong enough to show up on the overall test (P = 0.113). Taken together, these findings further support a role for IRF6 variants in clefting of the lip and provide specific risk estimates in a Norwegian population. C1 [Jugessur, Astanand; Lie, Rolv T.; Gjessing, Hakon K.; Nilsen, Roy M.] Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Sect Epidemiol & Med Stat, Bergen, Norway. [Rahimov, Fedik; Murray, Jeffrey C.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. [Lie, Rolv T.; Nguyen, Truc Trung] Norwegian Inst Publ Hlth, Med Birth Registry Norway, Bergen, Norway. [Wilcox, Allen J.] Natl Inst Environm Hlth Sci, Durham, NC USA. [Wilcox, Allen J.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Gjessing, Hakon K.] Norwegian Inst Publ Hlth, Oslo, Norway. RP Jugessur, A (reprint author), Royal Childrens Hosp, Murdoch Childrens Res Inst, Flemington Rd, Parkville, Vic 3052, Australia. EM anil.jugessur@mcri.edu.au RI Gjessing, Hakon/A-5871-2012; Rahimov, Fedik/H-2685-2013; OI Wilcox, Allen/0000-0002-3376-1311 FU Intramural NIH HHS; NIDCR NIH HHS [DE01960, DE08559, R01 DE008559, R01 DE008559-10, R37 DE008559, R37 DE008559-18, R37 DE008559-19] NR 24 TC 52 Z9 56 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JUL PY 2008 VL 32 IS 5 BP 413 EP 424 DI 10.1002/gepi.20314 PG 12 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 324VR UT WOS:000257548000003 PM 18278815 ER PT J AU Ciner, E Wojciechowski, R Ibay, G Bailey-Wilson, JE Stambolian, D AF Ciner, Elise Wojciechowski, Robert Ibay, Grace Bailey-Wilson, Joan E. Stambolian, Dwight TI Genomewide scan of ocular refraction in African-American families shows significant linkage to chromosome 7p15 SO GENETIC EPIDEMIOLOGY LA English DT Article DE ocular refraction; myopia; linkage; genetics; African-American ID HIGH MYOPIA MAPS; MULTILOCUS GENOTYPE DATA; WIDE SCAN; SUSCEPTIBILITY LOCUS; GENETIC-LOCI; SIB-PAIR; POPULATION; ERROR; AGGREGATION; INFERENCE AB Refractive development is influenced by environmental and genetic factors. Genetic studies have identified several regions of linkage to ocular refraction, but none have been carried out in African-derived populations. We performed quantitative trait locus linkage analyses in African-American (AA) families to identify genomic regions responsible for refraction. We recruited 493 AA individuals in 96 families to participate in the Myopia Family Study. Genotyping of 387 microsatellite markers was performed on 398 participants. The mean refraction among genotyped individuals was -2.87 D (SD = 3.58) and myopia of at least 1 D was present in 267 (68%) participants. Multipoint, regression-based, linkage analyses were carried out on a logarithmic transformation of ocular refraction using the statistical package MERLIN-REGRESS. Empirical significance levels were determined via 4,898 whole-genome gene-dropping simulations. Linkage analyses were repeated after clustering families into two subgroups based on admixture proportions as determined by the software package STRUCTURE. Genomewide significant linkage was seen at 47 cM on chromosome 7 (logarithm of the odds ratio (LOD) = 5.87, P = 0.00005). In addition, three regions on chromosomes 2p, 3p and 10p showed suggestive evidence of linkage (LOD > 2, P < 0.005) for ocular refraction. We mapped the first quantitative trait locus for ocular refraction in an AA population to chr.7p15. Two previous studies in European-derived families reported some evidence of linkage to a nearby region, suggesting that this region may contain polymorphisms that mediate refraction across populations. The genomic region under our linkage peak spans similar to 17 Mb and contains similar to 170 genes. Further refinement of this region will be pursued in future studies. C1 [Wojciechowski, Robert; Ibay, Grace; Bailey-Wilson, Joan E.] NHGRI, IDRB, NIH, Baltimore, MD 21231 USA. [Ciner, Elise] Penn Coll Optometry, Inst Eye, Philadelphia, PA 19141 USA. [Wojciechowski, Robert] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Stambolian, Dwight] Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA. [Stambolian, Dwight] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. RP Wojciechowski, R (reprint author), NHGRI, IDRB, NIH, 333 Cassell Dr,Suite 1200, Baltimore, MD 21231 USA. EM rwojciec@jhsph.edu OI Wojciechowski, Robert/0000-0002-9593-4652; Bailey-Wilson, Joan/0000-0002-9153-2920 FU NEI NIH HHS [R01 EY012226, R01 EY012226-05, EY12226, U10 EY012226]; NHGRI NIH HHS [N01HG65403] NR 42 TC 33 Z9 35 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JUL PY 2008 VL 32 IS 5 BP 454 EP 463 DI 10.1002/gepi.20318 PG 10 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 324VR UT WOS:000257548000007 PM 18293391 ER PT J AU Schaid, DJ McDonnell, SK Carlson, EE Thibodeau, SN Stanford, JL Ostrander, EA AF Schaid, Daniel J. McDonnell, Shannon K. Carlson, Erin E. Thibodeau, Stephen N. Stanford, Janet L. Ostrander, Elaine A. TI Searching for epistasis and linkage heterogeneity by correlations of pedigree-specific linkage scores SO GENETIC EPIDEMIOLOGY LA English DT Article DE epistasis; extreme values; gene-gene interaction; locus heterogeneity ID AFFECTED RELATIVE PAIRS; CANCER-SUSCEPTIBILITY LOCI; GENE-GENE INTERACTIONS; HIGH-RESOLUTION MAPS; AFFECTED SIB-PAIRS; PROSTATE-CANCER; FUNCTIONAL CONNECTIVITY; BOOTSTRAP APPROACH; MULTIPLE GENES; COMPLEX TRAITS AB Recognizing that multiple genes are likely responsible for common complex traits, statistical methods are needed to rapidly screen for either interacting genes or locus heterogeneity in genetic linkage data. To achieve this, some investigators have proposed examining the correlation of pedigree linkage scores between pairs of chromosomal regions, because large positive correlations suggest interacting loci and large negative correlations suggest locus heterogeneity (Cox et al. [1999]; Maclean et al. [1993]). However, the statistical significance of these extreme correlations has been difficult to determine due to the autocorrelation of linkage scores along chromosomes. In this study, we provide novel solutions to this problem by using results from random field theory, combined with simulations to determine the null correlation for syntenic loci. Simulations illustrate that our new methods control the Type-I error rates, so that one can avoid the extremely conservative Bonferroni correction, as well as the extremely time-consuming permutational method to compute P-values for nonsyntenic loci. Application of these methods to prostate cancer linkage studies illustrates interpretation of results and provides insights into the impact of marker information content on the resulting statistical correlations, and ultimately the asymptotic P-values. C1 [Schaid, Daniel J.; McDonnell, Shannon K.; Carlson, Erin E.] Mayo Clin, Biostat Sect, Coll Med, Div Biostat, Rochester, MN 55905 USA. [Thibodeau, Stephen N.] Mayo Clin, Coll Med, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Stanford, Janet L.] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. [Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Schaid, DJ (reprint author), Mayo Clin, Biostat Sect, Coll Med, Div Biostat, Harwick 775,200 1st St,SW, Rochester, MN 55905 USA. EM schaid@mayo.edu OI Ostrander, Elaine/0000-0001-6075-9738 FU Intramural NIH HHS; NCI NIH HHS [CA90754, CA78836, K05 CA090754, N01 CA015083, R01 CA072818, R01 CA078836, R01 CA080122, R01CA15083, R01CA72818, R01CA80122]; NIGMS NIH HHS [R01 GM067768, R01 GM067768-04, R01GM67768] NR 49 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JUL PY 2008 VL 32 IS 5 BP 464 EP 475 DI 10.1002/gepi.20319 PG 12 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 324VR UT WOS:000257548000008 PM 18330905 ER PT J AU Sharma, D Masison, DC AF Sharma, Deepak Masison, Daniel C. TI Functionally redundant isoforms of a yeast Hsp70 chaperone subfamily have different antiprion effects SO GENETICS LA English DT Article ID BETA-SHEET STRUCTURE; URE3 PRION PROPAGATION; SACCHAROMYCES-CEREVISIAE; PSI+ PRION; PROTEIN DISAGGREGATION; CYTOSOLIC HSP70; HSP104; PSI(+); HSP40; GENERATION AB Why eukaryotes encode multiple Hsp70 isoforms is unclear. Saccharomyces cerevisiae Ssa1p and Ssa2p are constitutive 98% identical Hsp70's. Stress-inducible Sssa3p and Ssa4p are 80% identical to Ssal/2p. We show Ssa1p-4p have distinct functions affecting [PSI+] and [URE3] prions. When expressed as the only SSa, Ssa1p antagonized [URE3] and Ssa2p antagonized [PSI+]. Ssa3p and Ssa1p influenced [URE3] and [PSI+] Somewhat differently but overall their effects paralleled those of Ssa1p and Ssa2p, respectively. Additionally, Ssa3p suppressed a prion-inhibitory effect of elevated temperature. Our previously described Ssa1-21p mutant weakens [PSI+] in SSA1-21 SSA2 cells and abolishes it in SSA1-21 ssa2 Delta cells. To test if the same mutation affected other prions or altered Ssa2p similarly, we compared effects of a constructed Ssa2-21p mutant and Ssa1-21p on both prions. Surprisingly, [URE3] was unaffected in SSA1-21 SSA2 cells and could propagate in SSA1-21 ssa2 Delta cells. Ssa2-21p impaired [URE3] considerably and weakened [PSI+] strongly but in a manner distinct from Ssa1-21p, highlighting functional differences between these nearly identical Hsp70's. our data uncover exquisite functional differences among isoforms of a highly homologous cytosolic Hsp70 subfamily and point to a possibility that variations in Hsp70 function that might improve fitness under optimal conditions are also important during stress. C1 [Sharma, Deepak; Masison, Daniel C.] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Masison, DC (reprint author), NIDDK, Lab Biochem & Genet, NIH, 8 Ctr Dr,Bldg 8,Room 407, Bethesda, MD 20892 USA. EM masisond@helix.nih.gov FU Intramural NIH HHS NR 48 TC 35 Z9 36 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD JUL PY 2008 VL 179 IS 3 BP 1301 EP 1311 DI 10.1534/genetics.108.089458 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 335TJ UT WOS:000258313400014 PM 18562668 ER PT J AU Usdin, K AF Usdin, Karen TI The biological effects of simple tandem repeats: Lessons from the repeat expansion diseases SO GENOME RESEARCH LA English DT Review ID FRAGILE-X-SYNDROME; CYSTATIN B GENE; FACIOSCAPULOHUMERAL MUSCULAR-DYSTROPHY; CEREBELLAR-TREMOR/ATAXIA-SYNDROME; PROGRESSIVE MYOCLONUS EPILEPSY; PREMATURE OVARIAN FAILURE; REPLICATION IN-VIVO; FMR1 MESSENGER-RNA; CGG-REPEAT; TRINUCLEOTIDE REPEAT AB Tandem repeats are common features of both prokaryote and eukaryote genomes, where they can be found not only in intergenic regions but also in both the noncoding and coding regions of a variety of different genes. The repeat expansion diseases are a group of human genetic disorders caused by long and highly polymorphic tandem repeats. These disorders provide many examples of the effects that such repeats can have on many biological processes. While repeats in the coding sequence can result in the generation of toxic or malfunctioning proteins, noncoding repeats can also have significant effects including the generation of chromosome fragility, the silencing of the genes in which they are located, the modulation of transcription and translation, and the sequestering of proteins involved in processes such as splicing and cell architecture. C1 NIDDKD, Sect Gene Struct & Dis, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. RP Usdin, K (reprint author), NIDDKD, Sect Gene Struct & Dis, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. EM ku@helix.nih.gov FU Intramural NIH HHS NR 138 TC 86 Z9 89 U1 5 U2 17 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JUL PY 2008 VL 18 IS 7 BP 1011 EP 1019 DI 10.1101/gr.070409.107 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 320QC UT WOS:000257249100001 PM 18593815 ER PT J AU Grice, EA Kong, HH Renaud, G Young, AC Bouffard, GG Blakesley, RW Wolfsberg, TG Turner, ML Segre, JA AF Grice, Elizabeth A. Kong, Heidi H. Renaud, Gabriel Young, Alice C. Bouffard, Gerard G. Blakesley, Robert W. Wolfsberg, Tyra G. Turner, Maria L. Segre, Julia A. CA Nisc Comparative Sequencing TI A diversity profile of the human skin microbiota SO GENOME RESEARCH LA English DT Article ID MOLECULAR ANALYSIS; SEQUENCE; ACNE; COMMUNITIES; ENVIRONMENT; VULGARIS; BACTERIA; PROGRAM; ECOLOGY; UNIFRAC AB The many layers and structures of the skin serve as elaborate hosts to microbes, including a diversity of commensal and pathogenic bacteria that contribute to both human health and disease. To determine the complexity and identity of the microbes inhabiting the skin, we sequenced bacterial 16S small-subunit ribosomal RNA genes isolated from the inner elbow of five healthy human subjects. This analysis revealed 113 operational taxonomic units (OTUs;"phylotypes") at the level of 97% similarity that belong to six bacterial divisions. To survey all depths of the skin, we sampled using three methods: swab, scrape, and punch biopsy. Proteobacteria dominated the skin microbiota at all depths of sampling. Interpersonal variation is approximately equal to intrapersonal variation when considering bacterial community membership and structure. Finally, we report strong similarities in the complexity and identity of mouse and human skin microbiota. This study of healthy human skin microbiota will serve to direct future research addressing the role of skin microbiota in health and disease, and metagenomic projects addressing the complex physiological interactions between the skin and the microbes that inhabit this environment. C1 [Grice, Elizabeth A.; Segre, Julia A.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Kong, Heidi H.; Turner, Maria L.] NCI, Dermatol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. [Renaud, Gabriel; Bouffard, Gerard G.; Blakesley, Robert W.; Wolfsberg, Tyra G.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Young, Alice C.; Bouffard, Gerard G.; Blakesley, Robert W.; Nisc Comparative Sequencing] NHGRI, Intramural Sequencing Ctr NISC, NIH, Bethesda, MD 20892 USA. RP Segre, JA (reprint author), NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. EM jsegre@nhgri.nih.gov RI Ducey, Thomas/A-6493-2011; OI Kong, Heidi/0000-0003-4424-064X; Grice, Elizabeth/0000-0003-3939-2200 NR 34 TC 277 Z9 292 U1 8 U2 56 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JUL PY 2008 VL 18 IS 7 BP 1043 EP 1050 DI 10.1101/gr.075549.107 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 320QC UT WOS:000257249100004 PM 18502944 ER PT J AU Hughes, AL Welch, R Puri, V Matthews, C Haque, K Chanock, SJ Yeager, M AF Hughes, Austin L. Welch, Robert Puri, Vinita Matthews, Casey Haque, Kashif Chanock, Stephen J. Yeager, Meredith TI Genorne-wide SNP typing reveals signatures of population history SO GENOMICS LA English DT Article DE single-nucleotide polymorphism; human populations; complex disease ID PROTEIN-CODING LOCI; NATURAL-SELECTION; AFRICAN POPULATIONS; RACIAL-DIFFERENCES; MOLECULAR-CLONING; POLYMORPHIC SITES; CANDIDATE GENES; HUMAN GENOME; HEALTH; AMERICANS AB Single-nucleotide polymorphism (SNP) arrays have become a popular technology for disease-association studies, but they also have potential for studying the genetic differentiation of human populations. Application of the Affymetrix GeneChip Human Mapping 500K Array Set to a population of 102 individuals representing the major ethnic groups in the United States (African, Asian, European, and Hispanic) revealed patterns of gene diversity and genetic distance that reflected population history. We analyzed allelic frequencies at 388,654 autosomal SNP sites that showed some variation in our study population and 10% or fewer missing values. Despite the small size (23-31 individuals) of each subpopulation, there were no fixed differences at any site between any two subpopulations. As expected from the African origin of modern humans, greater gene diversity was seen in Africans than in either Asians or Europeans, and the genetic distance between the Asian and the European populations was significantly lower than that between either of these two populations and Africans. Principal components analysis applied to a correlation matrix among individuals was able to separate completely the major continental groups of humans (Africans, Asians, and Europeans), while Hispanics overlapped all three of these groups. Genes containing two or more markers with extraordinarily high genetic distance between subpopulations were identified as candidate genes for health differences between subpopulations. The results show that, even with modest sample sizes, genome-wide SNP genotyping technologies have great promise for capturing signatures of gene frequency difference between human subpopulations, with applications in areas as diverse as forensics and the study of ethnic health disparities. (C) 2008 Elsevier Inc. All rights reserved. C1 [Hughes, Austin L.] Univ S Carolina, Dept Biol Sci, Columbia, SC 29208 USA. [Welch, Robert; Puri, Vinita; Matthews, Casey; Haque, Kashif; Yeager, Meredith] Natl Canc Inst FCRDC, Intramural Res Support Program, SAIC Frederick, Frederick, MD 21702 USA. [Welch, Robert; Puri, Vinita; Matthews, Casey; Haque, Kashif; Chanock, Stephen J.; Yeager, Meredith] NCI, Core Genotyping Facil, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Chanock, Stephen J.] NCI, Sect Genom Variat, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Hughes, AL (reprint author), Univ S Carolina, Dept Biol Sci, Columbia, SC 29208 USA. EM austin@biol.sc.edu FU NCI NIH HHS [N01-CO-12400, N01CO12400]; NIGMS NIH HHS [GM43940, R01 GM043940, R01 GM043940-19] NR 52 TC 14 Z9 14 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JUL PY 2008 VL 92 IS 1 BP 1 EP 8 DI 10.1016/j.ygeno.2008.03.005 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 323TK UT WOS:000257471100001 PM 18485661 ER PT J AU Banks, PM Chan, JKC Chan, WC Chott, A Favera, RD De Wolf-Peeters, C Delsol, GG Dyer, M Campo, E Falini, B Gascoyne, R Gatter, K Gaulard, P Grogan, T Harris, NL Isaacson, PG Jaffe, ES Kluin, PM Knowles, DM Mori, S Mueller-Hermelink, HK Nakamura, S Pileri, S Piris, M Ralfkiaer, E Siebert, R Stein, H Su, IJ Swerdlow, SH Warnke, R Weiss, L AF Banks, Peter M. Chan, John K. C. Chan, Wing C. (John) Chott, Andreas Favera, Riccardo Dalla De Wolf-Peeters, Christiane Delsol, G. Georges Dyer, Martin Campo, Elias Falini, Brunangelo Gascoyne, Randy Gatter, Kevin Gaulard, Philippe Grogan, Thomas Harris, Nancy Lee Isaacson, Peter G. Jaffe, Elaine S. Kluin, Philip M. Knowles, Daniel M. Mori, Shigeo Mueller-Hermelink, H. Konrad Nakamura, Shigeo Pileri, Stefano Piris, Miguel Ralfkiaer, Elisabeth Siebert, Reiner Stein, Harald Su, Ih-Jen Swerdlow, Steven H. Warnke, Roger Weiss, Lawrence TI David York Mason (1941-2008). Antibody wizard and a founder of modern hemopathology SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Biographical-Item C1 [Banks, Peter M.] Carolinas Med Ctr, Charlotte, NC 28203 USA. [Chan, John K. C.] Queen Elizabeth Hosp, Hong Kong, Hong Kong, Peoples R China. [Chan, Wing C. (John)] Univ Nebraska Med Ctr, Omaha, NE 68198 USA. [Chott, Andreas] Univ Vienna, A-1010 Vienna, Austria. [Favera, Riccardo Dalla] Columbia Univ, New York, NY 10027 USA. [De Wolf-Peeters, Christiane] Leuven Univ, Louvain, Belgium. [Delsol, G. Georges] Univ Toulouse, Toulouse, France. [Dyer, Martin] Univ Leicester, Leicester LE1 7RH, Leics, England. [Campo, Elias] Univ Barcelona, E-08007 Barcelona, Spain. [Falini, Brunangelo] Univ Perugia, I-06100 Perugia, Italy. [Gascoyne, Randy] BC Canc Agcy, Vancouver, BC, Canada. [Gatter, Kevin] Univ Oxford, Oxford OX1 2JD, England. [Gaulard, Philippe] Henri Mondor Hosp, Paris, France. [Grogan, Thomas] Univ Arizona, Tucson, AZ USA. [Harris, Nancy Lee] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Isaacson, Peter G.] Univ Coll, London, England. [Jaffe, Elaine S.] Natl Canc Inst, Bethesda, MD USA. [Kluin, Philip M.] Univ Groningen, NL-9700 AB Groningen, Netherlands. [Knowles, Daniel M.] Weill Cornell Med Coll, New York, NY USA. [Mori, Shigeo] Univ Tokyo, Tokyo 1138654, Japan. [Mueller-Hermelink, H. Konrad] Univ Wurzburg, D-97070 Wurzburg, Germany. [Nakamura, Shigeo] Nagoya Univ, Nagoya, Aichi 4648601, Japan. [Pileri, Stefano] Univ Bologna, I-40126 Bologna, Italy. [Piris, Miguel] CNIO, Madrid, Spain. [Ralfkiaer, Elisabeth] Univ Copenhagen, DK-1168 Copenhagen, Denmark. [Siebert, Reiner] Univ Kiel, D-24098 Kiel, Germany. [Stein, Harald] Univ Berlin, Berlin, Germany. [Swerdlow, Steven H.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Warnke, Roger] Stanford Univ, Stanford, CA 94305 USA. [Weiss, Lawrence] City Hope Natl Med Ctr, Duarte, CA 91010 USA. RP Banks, PM (reprint author), Carolinas Med Ctr, Charlotte, NC 28203 USA. EM bankspds@aol.com; jkcchan@ha.org.hk; jchan@unmc.edu; andreas.chott@meduniwien.ac.at; rd10@columbia.edu; christiane.peeters@uz.kuleuven.ac.be; delsol.g@chu-toulouse.fr; mjsd1@le.ac.uk; ecampo@clinic.ub.es; faliniem@unipg.it; rgascoyn@bccancer.bc.ca; kevin.gatter@ndcls.ox.ac.uk; philippe.gaulard@hmn.ap-hop-paris.fr; tmgrogan@u.arizona.edu; nlharris@partners.org; p.isaacson@ucl.ac.uk; elainejaffe@nih.gov; p.m.kluin@path.azg.nl; dknowles@med.cornell.edu; mori@ims.u-tokyo.ac.jp; path062@mail.uni-wuerzburg.de; snaka-mur@med.nagoia-u.ac.jp; pileri@orsola-malpighi.med.unibo.it; mapiris@cnio.es; eral@herlevhosp.kbhamt.dk; rsiebert@medgen.uni-kiel.de; harald.stein@charite.de; suihjen@ha.mc.ntu.edu.tw; swerdlowsh@upmc.edu; rwarnke@stan-ford.edu; lweiss@coh.org RI Siebert, Reiner/A-8049-2010 NR 1 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 JUL PY 2008 VL 93 IS 7 BP A EP B PG 2 WC Hematology SC Hematology GA 323CI UT WOS:000257421200037 ER PT J AU Alter, HJ AF Alter, H. J. TI Management of hepatitis virus infections SO HAEMOPHILIA LA English DT Article ID B-VIRUS; ADEFOVIR DIPIVOXIL; HEPATOCELLULAR-CARCINOMA; TREATMENT RESPONSE; UNITED-STATES; UPDATE; RISK; RECOMMENDATIONS; INTERFERON; PREVALENCE C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. RP Alter, HJ (reprint author), NIH, Dept Transfus Med, Bethesda, MD 20892 USA. EM halter@dtm.cc.nih.gov NR 28 TC 0 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD JUL PY 2008 VL 14 SU 3 BP 26 EP 32 DI 10.1111/j.1365-2516.2008.01739.x PG 7 WC Hematology SC Hematology GA 305NO UT WOS:000256185300004 PM 18510518 ER PT J AU Alter, HJ AF Alter, H. J. TI The natural and unnatural history of hepatitis C virus infection SO HAEMOPHILIA LA English DT Meeting Abstract C1 [Alter, H. J.] NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD JUL PY 2008 VL 14 SU 2 BP 38 EP 38 PG 1 WC Hematology SC Hematology GA 295VK UT WOS:000255501800202 ER PT J AU Chatterji, S Kowal, P Mathers, C Naidoo, N Verdes, E Smith, JP Suzman, R AF Chatterji, Somnath Kowal, Paul Mathers, Colin Naidoo, Nlrmala Verdes, Emese Smith, James P. Suzman, Richard TI The health of aging Populations in China and India SO HEALTH AFFAIRS LA English DT Article ID CHRONIC DISEASES AB China and India are home to two of the world's largest populations, and both populations are aging rapidly. Our data compare health status, risk factors, and chronic diseases among people age forty-five and older in China and India. By 2030, 65.6 percent of the Chinese and 45.4 percent of the Indian health burden are projected to be borne by older adults, a population with high levels of noncommunicable diseases. Smoking (26 percent in both China and India) and inadequate physical activity (10 percent and 17.7 percent, respectively) are highly prevalent. Health policy and interventions informed by appropriate data will be needed to avert this burden. C1 [Chatterji, Somnath; Kowal, Paul; Mathers, Colin; Naidoo, Nlrmala; Verdes, Emese] WHO, Measurement & Hlth Informat Syst, CH-1211 Geneva, Switzerland. [Smith, James P.] RAND, Santa Monica, CA USA. [Suzman, Richard] NIA, Behav & Social Res Program, Bethesda, MD 20892 USA. RP Chatterji, S (reprint author), WHO, Measurement & Hlth Informat Syst, CH-1211 Geneva, Switzerland. EM chatterjis@who.int OI Kowal, Paul/0000-0002-6314-8753 FU NIA NIH HHS [P01 AG022481, R01 AG040165] NR 19 TC 53 Z9 54 U1 1 U2 8 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD JUL-AUG PY 2008 VL 27 IS 4 BP 1052 EP 1063 DI 10.1377/hlthaff.27.4.1052 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 326CQ UT WOS:000257635900020 PM 18607041 ER PT J AU Kocher, DC Apostoaei, AI Henshaw, RW Hoffman, FO Schubauer-Berigan, MK Stancescu, DO Thomas, BA Trabalka, JR Gilbert, ES Land, CE AF Kocher, David C. Apostoaei, A. Iulian Henshaw, Russell W. Hoffman, F. Owen Schubauer-Berigan, Mary K. Stancescu, Daniel O. Thomas, Brian A. Trabalka, John R. Gilbert, Ethel S. Land, Charles E. TI Interactive RadioEpidemiological Program (IREP): A web-based tool for estimating probability of causation/assigned share of radiogenic cancers SO HEALTH PHYSICS LA English DT Article DE dose reconstruction; risk analysis; radiation risk; cancer ID ATOMIC-BOMB SURVIVORS; MORTALITY RISK; RADIATION; FRACTIONS; WORKERS AB The Interactive RadioEpidemiological Program (IREP) is a Web-based, interactive computer code that is used to estimate the probability that a given cancer in an individual was induced by given exposures to ionizing radiation. IREP was developed by a Working Group of the National Cancer Institute and Centers for Disease Control and Prevention, and was adopted and modified by the National Institute for Occupational Safety and Health (NIOSH) for use in adjudicating claims for compensation for cancer under the Energy Employees Occupational Illness Compensation Program Act of 2000. In this paper, the quantity calculated in IREP is referred to as "probability of causation/assigned share" (PC/AS). PC/AS for a given cancer in an individual is calculated on the basis of an estimate of the excess relative risk (ERR) associated with given radiation exposures and the relationship PC/AS = ERR/ERR+1. IREP accounts for uncertainties in calculating probability distributions of ERR and PC/AS. An accounting of uncertainty is necessary when decisions about granting claims for compensation for cancer are made on the basis of an estimate of the upper 99% credibility limit of PC/AS to give claimants the "benefit of the doubt." This paper discusses models and methods incorporated in IREP to estimate ERR and PC/AS. Approaches to accounting for uncertainty are emphasized, and limitations of IREP are discussed. Although IREP is intended to provide unbiased estimates of ERR and PC/AS and their uncertainties to represent the current state of knowledge, there are situations described in this paper in which NIOSH, as a matter of policy, makes assumptions that give a higher estimate of the upper 99% credibility limit of PC/AS than other plausible alternatives and, thus, are more favorable to claimants. C1 [Kocher, David C.; Apostoaei, A. Iulian; Hoffman, F. Owen; Thomas, Brian A.; Trabalka, John R.] SENES Oak Ridge Inc, Oak Ridge, TN 37830 USA. [Henshaw, Russell W.; Schubauer-Berigan, Mary K.] NIOSH, Cincinnati, OH 45226 USA. [Stancescu, Daniel O.] SRA Int Inc, Durham, NC 27713 USA. [Gilbert, Ethel S.; Land, Charles E.] NCI, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. RP Kocher, DC (reprint author), SENES Oak Ridge Inc, 102 Donner Dr, Oak Ridge, TN 37830 USA. EM dck@senes.com RI Schubauer-Berigan, Mary/B-3149-2009 OI Schubauer-Berigan, Mary/0000-0002-5175-924X FU Intramural NIH HHS [ZIA CP010131-18] NR 51 TC 33 Z9 34 U1 1 U2 3 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 JUL PY 2008 VL 95 IS 1 BP 119 EP 147 DI 10.1097/01.HP.0000291191.49583.f7 PG 29 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 313FJ UT WOS:000256726200014 PM 18545036 ER PT J AU Sullivan, HW Rothman, AJ AF Sullivan, Helen W. Rothman, Alexander J. TI When planning is needed: Implementation intentions and attainment of approach versus avoidance health goals SO HEALTH PSYCHOLOGY LA English DT Article DE avoidance goals; implementation intentions; plans; nutrition ID PERSONAL GOALS; ACHIEVEMENT; BEHAVIOR; MOTIVATION; PLANS AB Objective: This study tested whether forming implementation intentions is an effective strategy for attaining health goals focused on trying to avoid a negative state. Design: Participants chose to either eat more healthy snacks (i.e., an approach goal) or eat fewer unhealthy snacks (i.e., an avoidance goal) over two weeks and were randomly assigned to create an implementation intention to do this or not. Main outcome measures: The authors measured fat and calorie intake after one week and after two weeks. Results: After two weeks, the participants who ate most unhealthily were those who pursued an avoidance goal and did not form an implementation intention. Conclusion: These results suggest that forming implementation intentions for avoidance goal pursuit can help people attain important health goals. C1 NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, Bethesda, MD 20892 USA. NCI, Hlth Commun & Informat Res Branch, Behav Res Program, Div Canc Control & Populat Sci,NIH, Bethesda, MD 20892 USA. Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA. RP Sullivan, HW (reprint author), NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, 6130 Executive Blvd, Bethesda, MD 20892 USA. EM sullivhe@mail.nih.gov NR 24 TC 32 Z9 32 U1 2 U2 13 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD JUL PY 2008 VL 27 IS 4 BP 438 EP 444 DI 10.1037/0278-6133.27.4.438 PG 7 WC Psychology, Clinical; Psychology SC Psychology GA 329EH UT WOS:000257849200005 PM 18643001 ER PT J AU Berry, C Schenke, W Aletras, AH Hsu, L Wright, V Faranesh, A Lederman, RJ Arai, AE AF Berry, C. Schenke, W. Aletras, A. H. Hsu, L. Wright, V. Faranesh, A. Lederman, R. J. Arai, A. E. TI Recruitable coronary collateral supply and left ventricular stiffness are linked in acute myocardial infarction in swine SO HEART LA English DT Meeting Abstract CT Annual Scientific Conference of the British-Cardiovascular-Society/British-Society-for-Cardiovascular-Resear ch CY JUN 02-04, 2008 CL Manchester, ENGLAND SP British Cardiovasc Soc, British Soc Cardiovasc Res C1 [Berry, C.; Schenke, W.; Aletras, A. H.; Hsu, L.; Wright, V.; Faranesh, A.; Lederman, R. J.; 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 JUL PY 2008 VL 94 SU 2 BP A118 EP A119 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 306ZI UT WOS:000256286700228 ER PT J AU Berry, C Kellman, P Aletras, AH Mancini, C Chen, M Hsu, L Lederman, RJ Arai, AE AF Berry, C. Kellman, P. Aletras, A. H. Mancini, C. Chen, M. Hsu, L. Lederman, R. J. Arai, A. E. TI Characterisation and initial validation of area-at-risk derived by T2-magnetic resonance imaging in acute myocardial infarction SO HEART LA English DT Meeting Abstract CT Annual Scientific Conference of the British-Cardiovascular-Society/British-Society-for-Cardiovascular-Resear ch CY JUN 02-04, 2008 CL Manchester, ENGLAND SP British Cardiovasc Soc, British Soc Cardiovasc Res C1 [Berry, C.; Kellman, P.; Aletras, A. H.; Mancini, C.; Chen, M.; Hsu, L.; Lederman, R. J.; Arai, A. E.] NIH, Bethesda, MD 20892 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 JUL PY 2008 VL 94 SU 2 BP A74 EP A75 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 306ZI UT WOS:000256286700146 ER PT J AU Berry, C Kellman, P Aletras, AE Schenke, W Hsu, L Wright, V Faranesh, A Lederman, RJ Arai, AE AF Berry, C. Kellman, P. Aletras, A. E. Schenke, W. Hsu, L. Wright, V. Faranesh, A. Lederman, R. J. Arai, A. E. TI Preconditioning does not influence the occurrence of microvascular obstruction or haemorrhage revealed by magnetic resonance imaging in a pre-clinical model of acute reperfused myocardial infarction SO HEART LA English DT Meeting Abstract CT Annual Scientific Conference of the British-Cardiovascular-Society/British-Society-for-Cardiovascular-Resear ch CY JUN 02-04, 2008 CL Manchester, ENGLAND SP British Cardiovasc Soc, British Soc Cardiovasc Res C1 [Berry, C.; Kellman, P.; Aletras, A. E.; Schenke, W.; Hsu, L.; Wright, V.; Faranesh, A.; Lederman, R. J.; Arai, A. E.] NIH, Bethesda, MD 20892 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 JUL PY 2008 VL 94 SU 2 BP A75 EP A76 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 306ZI UT WOS:000256286700147 ER PT J AU Bei, T Tilkeridis, C Garantziotis, S Boikos, SA Kazakos, K Simopoulos, C Stratakis, CA AF Bei, Thalia Tilkeridis, Constantinos Garantziotis, Stavros Boikos, Sosipatros A. Kazakos, Konstantinos Simopoulos, Constantinos Stratakis, Constantine A. TI A novel, non-functional, COL1A1 polymorphism is not associated with lumbar disk disease in young male Greek subjects unlike that of the Sp1 site SO HORMONES-INTERNATIONAL JOURNAL OF ENDOCRINOLOGY AND METABOLISM LA English DT Article DE Collagen; COL1A1 polymorphism; Lumbar Disk Disease ID INTERVERTEBRAL DISC; I COLLAGEN; DEGENERATION; MATRIX; ALLELE AB OBJECTIVE: We recently reported the association of the Sp1 site polymorphism of the COL1A1 gene with lumbar disk disease (LDD). In the present study we searched for a different polymorphism of the COL1A1 gene (which is usually not in linkage disequilibrium with the Sp1 site) in subjects with LDD. DESIGN: Blood was collected from 24 Greek army recruits, aged 29 +/- 7.6 years, with LDD, and 66 healthy men, aged 26 +/- 4.38 years, matched for body mass index (BMI) and age, with normal BMD and with no history of trauma or fractures, who served as controls. DNA was extracted and the COL1A1 gene was sequenced. Of the control subjects, 12 were army recruits and 54 were selected from the general population. RESULTS: The four base-pair insertion polymorphism in the COL1A1 gene analyzed by polymerase chain reaction amplification of DNA produces two different fragments (alleles A1 and A2):14 patients (58.3%) were homozygous for A2A2, versus 35 controls (53%), while 3 patients (12.5%) were A1A1, and 8 of the control subjects (12%) had this genotype. There were no statistically significant differences in the presence of the two alleles of this polymorphism between patients with LDD and control subjects. CONCLUSIONS: A four base-pair insertion polymorphism of the COL1A1 gene is not associated with the presence of LDD in young males, unlike the Sp1 site polymorphism of the same gene. These data reinforce the association between LDD and the functional polymorphisms of the Sp1 site by showing that other polymorphic sites of the of the COL1A1 gene in the same population of patients are not linked to the disease. C1 [Stratakis, Constantine A.] NICHD, Sect Endocrinol & Genet, SEGEN, Program Dev Endocrinol & Genet,NIH, Bethesda, MD 20892 USA. [Tilkeridis, Constantinos; Kazakos, Konstantinos; Simopoulos, Constantinos] Democritus Univ Thrace, Alexandroupolis, Greece. [Garantziotis, Stavros] Hellen Armed Forces, Ctr Recruitment Mil Personnel Hlth Serv KEYG, Arta, Greece. RP Stratakis, CA (reprint author), NICHD, Sect Endocrinol & Genet, SEGEN, Program Dev Endocrinol & Genet,NIH, Bldg 10,CRC,Room 1-3330,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov RI Garantziotis, Stavros/A-6903-2009 OI Garantziotis, Stavros/0000-0003-4007-375X FU Intramural NIH HHS [ZIA HD000642-13] NR 12 TC 3 Z9 3 U1 0 U2 0 PU HELLENIC ENDOCRINE SOC PI ATHENS PA 14 ALEXANDRAS AVE, ATHENS, 106 82, GREECE SN 1109-3099 J9 HORM-INT J ENDOCRINO JI Horm.-Int. J. Endocrinol. Metab. PD JUL-SEP PY 2008 VL 7 IS 3 BP 251 EP 254 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 393HF UT WOS:000262363700007 PM 18694864 ER PT J AU Bandettini, PA Bullmore, ET AF Bandettini, Peter A. Bullmore, Edward T. TI Endogenous oscillations and networks in functional magnetic resonance imaging SO HUMAN BRAIN MAPPING LA English DT Editorial Material C1 Univ Cambridge, Behav & Clin Neurosci Inst, Cambridge CB2 2QQ, England. Univ Cambridge, Brain Mapping Unit, Cambridge CB2 2QQ, England. [Bandettini, Peter A.] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Bullmore, ET (reprint author), Univ Cambridge, Addenbrookes Hosp, Brain Mapping Unit, Dept Psychiat, Cambridge CB2 2QQ, England. EM etb23@cam.ac.uk RI Bullmore, Edward/C-1706-2012 OI Bullmore, Edward/0000-0002-8955-8283 FU Intramural NIH HHS [Z01 MH002783-06]; Medical Research Council [G0001354] NR 18 TC 24 Z9 24 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 EI 1097-0193 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD JUL PY 2008 VL 29 IS 7 BP 737 EP 739 DI 10.1002/hbm.20607 PG 3 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 312MB UT WOS:000256674400001 PM 18465798 ER PT J AU Birn, RM Murphy, K Bandettini, PA AF Birn, Rasmus M. Murphy, Kevin Bandettini, Peter A. TI The effect of respiration variations on independent component analysis results of resting state functional connectivity SO HUMAN BRAIN MAPPING LA English DT Article DE default-mode network; respiration; independent component analysis; functional connectivity; rest ID DEFAULT-MODE; HUMAN BRAIN; FMRI DATA; ACTIVITY FLUCTUATIONS; PHYSIOLOGICAL NOISE; HEALTHY-SUBJECTS; BOLD SIGNAL; MRI; AUTISM; HYPOTHESIS AB The analysis of functional connectivity in fMRI can be severely affected by cardiac and respiratory fluctuations. While some of these artifactual signal changes can be reduced by physiological noise correction routines, signal fluctuations induced by slower breath-to-breath changes in the depth and rate of breathing are typically not removed. These slower respiration-induced signal changes occur at low frequencies and spatial locations similar to the fluctuations used to infer functional connectivity, and have been shown to significantly affect seed-ROI or seed-voxel based functional connectivity analysis, particularly in the default mode network. In this study, we investigate the effect of respiration variations on functional connectivity maps derived from independent component analysis (ICA) of resting-state data. Regions of the default mode network were identified by deactivations during a lexical decision task. Variations in respiration were measured independently and correlated with the MRI time series data. ICA appears to separate the default mode network and the respiration-related changes in most cases. In some cases, however, the component automatically identified as the default mode network was the same as the component identified as respiration-related. Furthermore, in most cases the time series associated with the default mode network component was still significantly correlated with changes in respiration volume per time, suggesting that current methods of ICA may not completely separate respiration from the default mode network. An independent measure of the respiration provides valuable information to help distinguish the default mode network from respiration-related signal changes, and to assess the degree of residual respiration related effects. C1 [Birn, Rasmus M.; Murphy, Kevin; Bandettini, Peter A.] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Birn, RM (reprint author), NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, 10 Ctr Dr,Bldg 10,Rm 1D80, Bethesda, MD 20892 USA. EM rbirn@mail.nih.gov RI Murphy, Kevin/A-1581-2010 OI Murphy, Kevin/0000-0002-6516-313X FU Intramural NIH HHS [Z01 MH002783-06] NR 53 TC 155 Z9 157 U1 0 U2 8 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 JUL PY 2008 VL 29 IS 7 BP 740 EP 750 DI 10.1002/hbm.20577 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 312MB UT WOS:000256674400002 PM 18438886 ER PT J AU Li, QH Yu, K Li, ZH Zheng, G AF Li, Qizhai Yu, Kai Li, Zhaohai Zheng, Gang TI MAX-rank: a simple and robust genome-wide scan for case-control association studies SO HUMAN GENETICS LA English DT Article ID NUISANCE PARAMETER; CORRELATED TESTS; TREND TESTS; SAMPLE-SIZE; RISK; STATISTICS; MAXIMUM; CANCER; FAMILY AB In genome-wide association studies (GWAS), single-marker analysis is usually employed to identify the most significant single nucleotide polymorphisms (SNPs). The trend test has been proposed for analysis of case-control association. Three trend tests, optimal for the recessive, additive and dominant models respectively, are available. When the underlying genetic model is unknown, the maximum of the three trend test results (MAX) has been shown to be robust against genetic model misspecification. Since the asymptotic distribution of MAX depends on the allele frequency of the SNP, using the P-value of MAX for ranking may be different from using the MAX statistic. Calculating the P-value of MAX for 300,000 (300 K) or more SNPs is computationally intensive and the software and program to obtain the P-value of MAX are not widely available. On the other hand, the MAX statistic is very easy to calculate without complex computer programs. Thus, we study whether or not one could use the MAX statistic instead of its P-value to rank SNPs in GWAS. The approaches using the MAX and its P-value to rank SNPs are referred to as MAX-rank and P-rank. By applying MAX-rank and P-rank to simulated and four real datasets from GWAS, we found the ranks of SNPs with true association are very similar using both approaches. Thus, we recommend to use MAX-rank for genome-wide scans. After the top-ranked SNPs are identified, their P-values based on MAX can be calculated and compared with the significance level. C1 [Zheng, Gang] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. [Li, Qizhai; Yu, Kai] NCI, Biostat Branch, Bethesda, MD 20892 USA. [Li, Qizhai] Chinese Acad Sci, Acad Math & Syst Sci, Beijing 100080, Peoples R China. [Li, Zhaohai] George Washington Univ, Dept Stat, Washington, DC 20052 USA. [Li, Zhaohai] NICHHD, Biometry & Math Stat Branch, Rockville, MD 20852 USA. RP Zheng, G (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr,MSC 7913, Bethesda, MD 20892 USA. EM zhengg@nhlbi.nih.gov NR 25 TC 26 Z9 27 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JUL PY 2008 VL 123 IS 6 BP 617 EP 623 DI 10.1007/s00439-008-0514-8 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 312HF UT WOS:000256659100004 PM 18491142 ER PT J AU Simon-Sanchez, J Singleton, AB AF Simon-Sanchez, Javier Singleton, Andrew B. TI Sequencing analysis of OMI/HTRA2 shows previously reported pathogenic mutations in neurologically normal controls SO HUMAN MOLECULAR GENETICS LA English DT Article ID AUTOSOMAL-DOMINANT PARKINSONISM; PROTEASE HTRA2/OMI; ALZHEIMERS-DISEASE; CHROMOSOME 2P13; GENE; ONSET; ANTICIPATION; LOCUS; CLONING; FAMILY AB A novel heterozygous non-synonymous mutation and a novel polymorphism in OMI/HTRA2 locus have been associated with Parkinson's disease (PD) in a German population. In an attempt to replicate these results in an independent population, we analyzed the entire coding region of OMI/HTRA2 in a series of 644 North American PD cases with both young- and late-onset disease and in 828 North American neurologically normal controls. Our results show that neither of the variants previously related to PD were associated with PD in our cohort and that the risk variants were present in neurologically normal controls. C1 [Simon-Sanchez, Javier; Singleton, Andrew B.] NIA, Mol Genet Unit, Neurogenet Lab, IRP,NIH, Bethesda, MD 20892 USA. [Simon-Sanchez, Javier] CSIC, Inst Biomed Valencia, Dept Genom & Prote, Unidad Genet Mol, Valencia 46010, Spain. [Singleton, Andrew B.] Univ Virginia, Ctr Publ Hlth Genom, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA. RP Singleton, AB (reprint author), NIA, Mol Genet Unit, Neurogenet Lab, IRP,NIH, Room 1A1014,Bldg 35,35 Lincoln Dr, Bethesda, MD 20892 USA. EM singleta@mail.nih.gov RI Singleton, Andrew/C-3010-2009 FU Intramural NIH HHS [Z01 AG000957-05] NR 26 TC 69 Z9 70 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 JUL 1 PY 2008 VL 17 IS 13 BP 1988 EP 1993 DI 10.1093/hmg/ddn096 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 316VQ UT WOS:000256978200011 PM 18364387 ER PT J AU Chou, JY Mansfield, BC AF Chou, Janice Y. Mansfield, Brian C. TI Mutations in the glucose-6-phosphatase-alpha (G6PC) gene that cause type Ia glycogen storage disease SO HUMAN MUTATION LA English DT Review DE glucose-6-phosphatase-alpha; G6PC; glycogen storage disease type Ia; GSD-Ia; phenotype-genotype ID PHOSPHOHISTIDINE-ENZYME INTERMEDIATE; CHINESE PATIENTS; JAPANESE PATIENTS; NEUTROPHIL DYSFUNCTION; MOLECULAR DIAGNOSIS; CHROMOSOME 11Q23; TRANSLOCASE GENE; TURKISH PATIENTS; CLINICAL COURSE; POINT MUTATION AB Glucose-6-phosphatase-alpha (G6PC) is a key enzyme in glucose homeostasis that catalyzes the hydrolysis of glucose-6-phosphate to glucose and phosphate in the terminal step of gluconeogenesis and glycogenolysis. Mutations in the G6PC gene, located on chromosome 17q21, result in glycogen storage disease type Ia (GSD-Ia), an autosomal recessive metabolic disorder. GSD-Ia patients manifest a disturbed glucose homeostasis, characterized by fasting hypoglycemia, hepatomegaly, nephromegaly, hyperlipidemia, hyperuricemia, lactic acidemia, and growth retardation. G6PC is a highly hydrophobic glycoprotein, anchored in the membrane of the endoplasmic reticulum with the active center facing into the lumen. To date, 54 missense, 10 nonsense, 17 insertion/deletion, and three splicing mutations in the G6PC gene have been identified in more than 550 patients. Of these, 50 missense, two nonsense, and two insertion/deletion mutations have been functionally characterized for their effects on enzymatic activity and stability. While GSD-Ia is not more prevalent in any ethnic group, mutations unique to Caucasian, Oriental, and Jewish populations have been described. Despite this, GSD-Ia patients exhibit phenotypic heterogeneity and a stringent genotype-phenotype relationship does not exist. C1 [Chou, Janice Y.] Natl Inst Child Hlth & Human Dev, Natl Inst Hlth, Sect Cellular Differentiat, Heritable Disorders Branch, Bethesda, MD USA. [Mansfield, Brian C.] Correlog Syst Inc, Rockville, MD USA. RP Chou, JY (reprint author), Bldg 10,Room 9D42,10 Ctr Dr, Bethesda, MD 20892 USA. EM chouja@mail.nih.gov OI Mansfield, Brian/0000-0002-8533-2789 FU Intramural NIH HHS [Z01 HD000912-28] NR 104 TC 42 Z9 45 U1 0 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD JUL PY 2008 VL 29 IS 7 BP 921 EP 930 DI 10.1002/humu.20772 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 323WR UT WOS:000257479600004 PM 18449899 ER PT J AU Kovacic, MB Katki, HA Kreimer, AR Sherman, ME AF Kovacic, Melinda Butsch Katki, Hormuzd A. Kreimer, Aimee R. Sherman, Mark E. TI Epidemiologic analysis of histologic cervical inflammation: relationship to human papillomavirus infections SO HUMAN PATHOLOGY LA English DT Article DE histology; cervical intraepithelial neoplasia; human papillomavirus; immune infiltrates; inflammation; stroma; epithelium; smoking; oral contraceptives; STDs ID INTRAEPITHELIAL NEOPLASIA; UTERINE CERVIX; LANGERHANS CELLS; HPV INFECTION; SMOKING; WOMEN; ASSOCIATION; LYMPHOCYTES; SECRETIONS; REGRESSION AB Infections with carcinogenic human papillomaviruses, the causal agents of cervical intraepithelial neoplasia and cancer, as well as infections with noncarcinogenic human papillomaviruses, are common but typically resolve spontaneously. Effective cell-mediated immune responses are critical for human papillomavirus clearance; however, data relating cervical inflammation to the outcome of human papillomavirus infection are lacking. To investigate this topic, we performed a masked parallel review of inflammation in the stroma and epithelium of cervical biopsies (n = 564) collected from a retrospectively defined subcohort of women systematically followed up in the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study. Women in our analysis had undergone colposcopically directed enrollment biopsies diagnosed as negative or cervical intraepithelial neoplasia I and had corresponding human papillomavirus polymerase chain reaction test results of negative (n = 250), positive for a single carcinogenic (n = 237), or noncarcinogenic (n = 81) type. Inflammation in cervical stroma varied with cofactors for human papillomavirus progression: current smokers showed less inflammation (odds ratio, 0.55: 95% confidence interval, 0.31-0.97), whereas current oral contraceptive users had increased inflammation (odds ratio, 1.7; 95% confidence interval, 0.92-3.0) as did those with a self-reported 2-year history of a sexually transmitted disease (odds ratio, 1.9; 95% confidence interval, 1.0-3.5). Biopsies of women with carcinogenic human papillomaviruses had greater inflammation within the epithelium (odds ratio, 1.6; 95% confidence interval, 1.1-2.3) compared with human papillomavirus-negative women. Associations with human papillomavirus type-specific persistence or progression to histologic cervical intraepithelial neoplasia 3 were diminished among women with moderate or marked inflammation in stroma (odds ratio, 0.49; 95% confidence interval, 0.25-0.99) or within epithelium (odds ratio, 0.51; 95% confidence interval, 0.26-0.97). These data suggest that cervical inflammation varies with human papillomavirus cofactors, type of human papillomavirus infection, and risk of persistence and progression. Additional studies are needed to confirm and extend these findings. (c) 2008 Published by Elsevier Inc. C1 [Kovacic, Melinda Butsch] Cincinnati Childrens Hosp Med Ctr, Inst Personalized & Predict Med, Cincinnati, OH 45229 USA. [Katki, Hormuzd A.; Sherman, Mark E.] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Rockville, MD 20852 USA. [Kreimer, Aimee R.] NCI, Canc Prevent Div, NIH, US Dept HHS, Rockville, MD 20852 USA. RP Kovacic, MB (reprint author), Cincinnati Childrens Hosp Med Ctr, Inst Personalized & Predict Med, Cincinnati, OH 45229 USA. EM melinda.butsch.kovacic@cchmc.org RI Katki, Hormuzd/B-4003-2015; Kreimer, Aimee/H-1687-2015 NR 30 TC 11 Z9 11 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD JUL PY 2008 VL 39 IS 7 BP 1088 EP 1095 DI 10.1016/j.humpath.2007.12.002 PG 8 WC Pathology SC Pathology GA 320VX UT WOS:000257264300015 PM 18495212 ER PT J AU Carter, BL Einhorn, PT Brands, M He, J Cutler, JA Whelton, PK Bakris, GL Brancati, FL Cushman, WC Oparil, S Wright, JT AF Carter, Barry L. Einhorn, Paula T. Brands, Michael He, Jiang Cutler, Jeffrey A. Whelton, Paul K. Bakris, George L. Brancati, Frederick L. Cushman, William C. Oparil, Suzanne Wright, Jackson T., Jr. TI Thiazide-Induced Dysglycemia Call for Research From a Working Group From the National Heart, Lung, and Blood Institute SO HYPERTENSION LA English DT Review ID LIPID-LOWERING TREATMENT; ATTACK TRIAL ALLHAT; ISOLATED SYSTOLIC HYPERTENSION; CONVERTING-ENZYME-INHIBITOR; DIABETES-MELLITUS; GLUCOSE-INTOLERANCE; LONG-TERM; ANTIHYPERTENSIVE TREATMENT; BETA-BLOCKERS; POTASSIUM HOMEOSTASIS C1 [Carter, Barry L.] Univ Iowa, Coll Pharm, Div Clin & Adm Pharm, Iowa City, IA 52242 USA. [Carter, Barry L.] Roy J & Lucille A Carver Coll Med, Dept Family Med, Iowa City, IA USA. [Einhorn, Paula T.; Cutler, Jeffrey A.] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA. [Brands, Michael] Med Coll Georgia, Dept Physiol, Augusta, GA 30912 USA. [He, Jiang] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA 70118 USA. [Whelton, Paul K.] Loyola Univ, Med Ctr, Chicago, IL 60611 USA. [Bakris, George L.] Univ Chicago, Hypertens Dis Unit, Chicago, IL 60637 USA. [Brancati, Frederick L.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Brancati, Frederick L.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Cushman, William C.] Univ Tennessee, Coll Med, Memphis Vet Affairs Med Ctr, Memphis, TN USA. [Cushman, William C.] Univ Tennessee, Coll Med, Dept Prevent Med & Med, Memphis, TN USA. [Oparil, Suzanne] Univ Alabama Birmingham, Dept Physiol & Med Biophys, Div Cardiovasc Dis, Birmingham, AL USA. [Wright, Jackson T., Jr.] Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Carter, BL (reprint author), Univ Iowa, Coll Pharm, Div Clin & Adm Pharm, Rm 527, Iowa City, IA 52242 USA. EM barry.carter@uiowa.edu FU NIDDK NIH HHS [P30 DK079637] NR 70 TC 51 Z9 60 U1 1 U2 1 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 JUL PY 2008 VL 52 IS 1 BP 30 EP 36 DI 10.1161/HYPERTENSIONAHA.108.114389 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 315KX UT WOS:000256880000003 PM 18504319 ER PT J AU Murphy, AJ Remaley, AT Sviridov, D Chin-Dusting, J AF Murphy, A. J. Remaley, A. T. Sviridov, D. Chin-Dusting, J. TI APOLIPOPROTEIN A-1 MIMETIC PEPTIDES INHIBIT MONOCYTE ADHESION TO FIBRINOGEN BY MODULATING CD11b EXPRESSION SO HYPERTENSION LA English DT Meeting Abstract CT 29th Annual Scientific Meeting of the High-Blood-Pressure-Research-Council-of-Australia CY DEC 05-08, 2007 CL Adelaide, AUSTRALIA SP High Blood Pressure Res Council Australia C1 [Murphy, A. J.; Sviridov, D.; Chin-Dusting, J.] Baker Heart Res Inst, Melbourne, Vic, Australia. [Remaley, A. T.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUL PY 2008 VL 52 IS 1 MA 044 BP 173 EP 173 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 315KX UT WOS:000256880000069 ER PT J AU Parker, DS Hsiao, RL Xing, Y Resch, AM Lee, CJ AF Parker, Douglass Stott Hsiao, Ruey-Lung Xing, Yi Resch, Alissa M. Lee, Christopher J. TI Solving the problem of trans-genomic query with alignment tables SO IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS LA English DT Article ID HUMAN EXPRESSED SEQUENCES; WIDE DETECTION; SPLICE FORMS; HUMAN GENES; MOUSE; DATABASE; CONSERVATION; PROTEOME; ISOFORMS; EVENTS AB The trans-genomic query (TGQ) problem-enabling the free query of biological information, even across genomes-is a central challenge facing bioinformatics. Solutions to this problem can alter the nature of the field, moving it beyond the jungle of data integration and expanding the number and scope of questions that can be answered. An alignment table is a binary relationship on locations (sequence segments). An important special case of alignment tables are hit tables-tables of pairs of highly similar segments produced by alignment tools like BLAST. However, alignment tables also include general binary relationships and can represent any useful connection between sequence locations. They can be curated and provide a high-quality queryable backbone of connections between biological information. Alignment tables thus can be a natural foundation for TGQ, as they permit a central part of the TGQ problem to be reduced to purely technical problems involving tables of locations. Key challenges in implementing alignment tables include efficient representation and indexing of sequence locations. We define a location data type that can be incorporated naturally into common off-the-shelf database systems. We also describe an implementation of alignment tables in BLASTGRES, an extension of the open-source POSTGRESQL database system that provides indexing and operators on locations required for querying alignment tables. This paper also reviews several successful large-scale applications of alignment tables for TGQ. Tables with millions of alignments have been used in queries about alternative splicing, an area of genomic analysis concerning the way in which a single gene can yield multiple transcripts. Comparative genomics is a large potential application area for TGQ and alignment tables. C1 [Xing, Yi] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. [Resch, Alissa M.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Lee, Christopher J.] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA. [Parker, Douglass Stott; Hsiao, Ruey-Lung] Univ Calif Los Angeles, Dept Comp Sci, Los Angeles, CA 90095 USA. RP Parker, DS (reprint author), Univ Calif Los Angeles, Ctr Comp Biol, Los Angeles, CA 90024 USA. EM stott@cs.ucla.edu; rlhsiao@cs.ucla.edu; yi-xing@uiowa.edu; resch@ncbi.nlm.nih.gov; leec@chem.ucla.edu RI Xing, yi/E-2884-2010 NR 49 TC 1 Z9 1 U1 0 U2 1 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA SN 1545-5963 J9 IEEE ACM T COMPUT BI JI IEEE-ACM Trans. Comput. Biol. Bioinform. PD JUL-SEP PY 2008 VL 5 IS 3 BP 432 EP 447 DI 10.1109/TCBB.2007.1073 PG 16 WC Biochemical Research Methods; Computer Science, Interdisciplinary Applications; Mathematics, Interdisciplinary Applications; Statistics & Probability SC Biochemistry & Molecular Biology; Computer Science; Mathematics GA 330ZP UT WOS:000257981800011 PM 18670046 ER PT J AU Brass, DM Yang, IV Kennedy, MP Whitehead, GS Rutledge, H Burch, LH Schwartz, DA AF Brass, David M. Yang, Ivana V. Kennedy, Marcus P. Whitehead, Gregory S. Rutledge, Holly Burch, Lauranell H. Schwartz, David A. TI Fibroproliferation in LPS-induced airway remodeling and bleomycin-induced fibrosis share common patterns of gene expression SO IMMUNOGENETICS LA English DT Article DE extracellular matrix; lipopolysaccharide; transforming growth factor beta 1 (TGF-beta 1); asthma; microarray; fibrosis; airway disease ID OSTEOCLAST DIFFERENTIATION; PULMONARY-FIBROSIS; INTERFERON-GAMMA; RANK LIGAND; IN-VIVO; DISEASE; CHEMOKINE; LIPOPOLYSACCHARIDE; LUNG; ASTHMA AB Chronic LPS inhalation causes submucosal thickening and airway narrowing. To address the hypothesis that environmental airway disease is, in part, a fibroproliferative lung disease, we exposed C57BL/6 mice daily to LPS by inhalation for up to 2 months followed by 1 month of recovery. C57BL/6 mice exposed to daily inhaled LPS had significantly enhanced mRNA expression of TGF-beta 1, TIMP-1, fibronectin-1, and pro-collagen types I, III, and IV and show prominent submucosal expression of the myofibroblast markers desmin and alpha-smooth muscle actin. To further characterize global gene expression in airway fibroproliferation, we performed microarray analysis on total lung RNA from mice exposed to LPS both acutely and chronically. This analysis revealed a subset of genes typically associated with lung injury and repair, and ECM homeostasis. To further identify candidate genes specifically involved in generic fibroproliferation, we interrogated this analysis with genes induced in C57BL/6 mouse lung by bleomycin. This analysis yielded a list of 212 genes in common suggesting that there is a common subset of genes that regulate fibroproliferation in the lung independent of etiologic agent and site of injury. C1 [Brass, David M.] Duke Univ, Med Ctr, Dept Pediat Neonatol, Durham, NC 27710 USA. [Yang, Ivana V.; Rutledge, Holly; Schwartz, David A.] NHLBI, Lab Environm Lung Dis, Natl Heart Lung & Blood Inst, Res Triangle Pk, NC 27709 USA. [Kennedy, Marcus P.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Whitehead, Gregory S.; Burch, Lauranell H.] NIEHS, Lab Resp Biol, Res Triangle Pk, NC 27709 USA. RP Brass, DM (reprint author), Duke Univ, Med Ctr, Dept Pediat Neonatol, 403 Alex R Sands Lab Bldg,DUMC 3373, Durham, NC 27710 USA. EM david.brass@duke.edu FU Intramural NIH HHS; NIEHS NIH HHS [ES07498, ES09607, ES11375] NR 39 TC 9 Z9 10 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD JUL PY 2008 VL 60 IS 7 BP 353 EP 369 DI 10.1007/s00251-008-0293-3 PG 17 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 322KA UT WOS:000257372600002 PM 18553078 ER PT J AU Park, DU Jin, KW Koh, DH Kim, BK Kim, KS Park, DY AF Park, Dong-Uk Jin, Ku-Won Koh, Dong-Hee Kim, Byung-Kyu Kim, Kyu-Sang Park, Doo-Yong TI A survey for rhinitis in an automotive ring manufacturing plant SO INDUSTRIAL HEALTH LA English DT Article DE rhinitis; metalworking fluids (MWF); MWF aerosol; grinding operation ID METAL-WORKING FLUIDS; ALLERGIC RHINITIS; RESPIRATORY SYMPTOMS; METALWORKING FLUIDS; EXPOSURE ASSESSMENT; WORKERS; ASTHMA; RISK; AIRWAY; ONSET AB We report findings regarding otolaryngologist-confirmed rhinitis, current exposure to MWF aerosols, fungi, and endotoxins for workers in a plant manufacturing automobile piston rings. Questionnaire data showed that 61.5% of 187 workers exhibited rhinitis-related symptoms. Rhinitis was confirmed in 99 of 115 workers whom were medically examined. Otolaryngologist-confirmed rhinitis was present in 10 of 19 grinding workers (52.6%), 67 of 142 production workers (47.2%), and 22 of 26 quality control (QC) workers (84.6%). These rates are much higher than the rates of rhinitis-related symptoms in automobile plants and other occupational settings and quite high even allowing for the common occurrence of rhinitis in the general population. We found that rhinitis could develop even in workers exposed to less than 0.5 mg/m(3) MWF aerosol. The average exposure to fungi exceeded 10 x 10(3) CFU/m(3), a level higher than that reported for other automobile plants. Although we were unable to identify significant risk factors for rhinitis using only the physician-confirmed rhinitis cases, this study concludes that exposure to MWF aerosol, which would include microbes and metals, could contribute to a high occurrence of rhinitis in grinding and production workers. Forty-nine workers (63.6%) of 77 rhinitis patients in grinding and production operations were determined to handle synthetic MWF directly. For QC workers, for whom the prevalence of physician-confirmed rhinitis was highest, exposure to a low level of MWF aerosol, including specific microbe species we couldn't identify, bright light, dry air, and certain work characteristics during inspection are possible risk factors for development of rhinitis. Further studies including identification of fungi species should be conducted so a firm conclusion can be made regarding the development of rhinitis in QC manufacturing plant workers. C1 [Park, Dong-Uk; Jin, Ku-Won] Korea Natl Open Univ, Dept Environm Hlth, Seoul 110791, South Korea. [Koh, Dong-Hee; Kim, Byung-Kyu; Kim, Kyu-Sang; Park, Doo-Yong] Occupat Safety & Hlth Res Inst, Ctr Occupat Dis Res, Kosha, South Korea. [Park, Dong-Uk] NCI, Occupat & Environm Epidemiol Branch Div Canc Epid, NIH, DHHS, Bethesda, MD 20892 USA. [Park, Doo-Yong] Hansung Univ, Seoul, South Korea. RP Park, DU (reprint author), Korea Natl Open Univ, Dept Environm Hlth, Seoul 110791, South Korea. RI Go, Donghee/I-7774-2012 NR 40 TC 5 Z9 5 U1 0 U2 1 PU NATL INST OCCUPATIONAL SAFETY & HEALTH, JAPAN PI KAWASAKI KANAGAWA PA 21-1 NAGAO 6-CHOME TAMA-KU, KAWASAKI KANAGAWA, 214, JAPAN SN 0019-8366 J9 IND HEALTH JI Ind. Health PD JUL PY 2008 VL 46 IS 4 BP 397 EP 403 DI 10.2486/indhealth.46.397 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 332PU UT WOS:000258096400013 PM 18716389 ER PT J AU Cote, LR Bornstein, MH Haynes, OM Bakeman, R AF Cote, Linda R. Bornstein, Marc H. Haynes, O. Maurice Bakeman, Roger TI Mother-infant person- and object-directed interactions in Latino immigrant families: A comparative approach SO INFANCY LA English DT Review ID COGNITIVE COMPETENCE; YOUNG-CHILDREN; RESPONSIVENESS; COMMUNICATION; SPECIFICITY; STABILITY; BEHAVIOR; CULTURES; PARENTS; ORIGIN AB Cultural variation in durations, relations, and contingencies of mother-infant person- and object-directed behaviors were examined for 121 nonmigrant Latino mother-infant dyads in South America, Latina immigrants from South America and their infants living in the United States, and European American mother-infant dyads. Nonmigrant Latina mothers and infants engaged in person-directed behaviors longer than Latino immigrant or European American mothers and infants. Mother and infant person-directed behaviors were positively related; mother and infant object-related behaviors were related for some cultural groups but not others. Nearly all mother and infant behaviors were mutually contingent. Mothers were more responsive to infants' behaviors than infants were to mothers. Some cultural differences in responsiveness emerged. Immigrant status has a differentiated role in mother-infant interactions. C1 [Cote, Linda R.; Bornstein, Marc H.; Haynes, O. Maurice] Eunice Kennedy Shriver Natl Inst Child & Human De, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Bakeman, Roger] Georgia State Univ, Dept Psychol, Atlanta, GA 30303 USA. RP Bornstein, MH (reprint author), Eunice Kennedy Shriver Natl Inst Child & Human De, NIH, US Dept HHS, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. EM Marc-H-Bornstein@nih.gov FU Intramural NIH HHS [ZIA HD001119-24] NR 117 TC 6 Z9 6 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1525-0008 J9 INFANCY JI Infancy PD JUL-AUG PY 2008 VL 13 IS 4 BP 338 EP 365 DI 10.1080/15250000802189386 PG 28 WC Psychology, Developmental SC Psychology GA 335YA UT WOS:000258330300003 PM 23275761 ER PT J AU Burtnick, MN Brett, PJ Nair, V Warawa, JM Woods, DE Gherardini, FC AF Burtnick, Mary N. Brett, Paul J. Nair, Vinod Warawa, Jonathan M. Woods, Donald E. Gherardini, Frank C. TI Burkholderia pseudomallei type III secretion system mutants exhibit delayed vacuolar escape phenotypes in RAW 264.7 murine macrophages SO INFECTION AND IMMUNITY LA English DT Article ID ACTIN-BASED MOTILITY; INTRACELLULAR SURVIVAL; PSEUDOMONAS-PSEUDOMALLEI; VIRULENCE DETERMINANT; POSSIBLE MECHANISM; CELL-FORMATION; MELIOIDOSIS; MALLEI; IDENTIFICATION; BACTERIA AB Burkholderia pseudomallei is a facultative intracellular pathogen capable of surviving and replicating within eukaryotic cells. Recent studies have shown that B. pseudomallei Bsa type III secretion system 3 (T3SS-3) mutants exhibit vacuolar escape and replication defects in J774.2 murine macrophages. In the present study, we characterized the interactions of a B. pseudomallei bsaZ mutant with RAW 264.7 marine macrophages. Following uptake, the mutant was found to survive and replicate within infected RAW 264.7 cells over an 18-h period. In addition, high levels of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), and RANTES, but not IL-1 alpha and IL-1 beta, were detected in culture supernatants harvested from infected monolayers. The subcellular location of B. pseudomallei within infected RAW 264.7 cells was determined, and as expected, the bsaZ mutant demonstrated early-vacuolar-escape defects. Interestingly, however, experiments also indicated that this mutant was capable of delayed vacuolar escape. Consistent with this finding, evidence of actin-based motility and multinucleated giant cell formation were observed between 12 and 18 h postinfection. Further studies demonstrated that a triple mutant defective in all three B. pseudomallei T3SSs exhibited the same phenotype as the bsaZ mutant, indicating that functional T3SS-1 and T3SS-2 did not appear to be responsible for the delayed escape phenotype in RAW 264.7 cells. Based upon these findings, it appears that B. pseudomallei may not require T3SS-1, -2, and -3 to facilitate survival, delayed vacuolar escape, and actin-based motility in activated RAW 264.7 macrophages. C1 [Burtnick, Mary N.; Brett, Paul J.; Warawa, Jonathan M.; Gherardini, Frank C.] NIAID, NIH, Rocky Mt Labs, Lab Zoonot Pathogens, Hamilton, MT 59840 USA. [Nair, Vinod] NIAID, NIH, Rocky Mt Labs, RTB,Res Technol Sect, Hamilton, MT 59840 USA. [Woods, Donald E.] Univ Calgary, Hlth Sci Ctr, Dept Microbiol & Infect Dis, Calgary, AB T2N 4N1, Canada. RP Gherardini, FC (reprint author), NIAID, NIH, Rocky Mt Labs, Lab Zoonot Pathogens, 903 S 4th, Hamilton, MT 59840 USA. EM fgherardini@niaid.nih.gov FU Intramural NIH HHS NR 46 TC 45 Z9 46 U1 1 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2008 VL 76 IS 7 BP 2991 EP 3000 DI 10.1128/IAI.00263-08 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 319OC UT WOS:000257172300019 PM 18443088 ER PT J AU Edwards, RA Wang, KH Davis, JS Birnbaumer, L AF Edwards, Robert A. Wang, Kehui Davis, Jennifer S. Birnbaumer, Lutz TI Role for epithelial dysregulation in early-onset colitis-associated colon cancer in Gi2-alpha-/- mice SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE colitis associated colon cancer; inflammatory bowel disease; animal models of colon cancer; heterotrimeric G-protein signaling ID INFLAMMATORY-BOWEL-DISEASE; COLORECTAL-CANCER; ULCERATIVE-COLITIS; MICROSATELLITE INSTABILITY; PHOSPHOLIPASE A(2); ARACHIDONIC-ACID; MUTANT; DYSPLASIA; THERAPY; SUBUNIT AB Background: Inflammatory bowel disease (IBD) is a risk factor for developing colorectal cancer but the mechanisms are poorly characterized. Mice lacking the G-protein alpha subunit Gi2-alpha spontaneously develop colitis and colon cancer with high penetrance. Compared to canonical Wnt/APC signaling-based animal models of colon cancer, the tumors in Gi2-alpha-/- mice more closely recapitulate the features of IBD-associated cancers seen in humans. They are predominantly right-sided, multifocal, mucinous, and arise from areas of flat dysplasia. Methods: In evaluating the potential contribution of epithelial Gi2-alpha signaling to this phenotype, we found that Gi2-alpha-/- colonic epithelium is hyperproliferative even before the onset of colitis, and resistant to the induction of apoptosis. We generated colon cancer cell lines overexpressing dominant-negative Gi2-alpha. Results: Like other cells lacking Gi2-alpha, these cells release less arachidonic acid, an important antiinflammatory and epithelial growth regulator. They are also hyperproliferative and resistant to camptothecin-induced apoptosis and caspase-3 activation. Conclusions: The colitis-associated cancers in Gi2-alpha-/- mice appear very similar to those seen in human IBD patients, and Gi2-alpha is a direct negative regulator of colonic epithelial cell growth. C1 [Edwards, Robert A.; Wang, Kehui; Davis, Jennifer S.] Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA 92697 USA. [Birnbaumer, Lutz] Natl Inst Environm Hlth Sci, Lab Signal Transduct, Res Triangle Pk, NC USA. RP Edwards, RA (reprint author), Univ Calif Irvine, Dept Pathol & Lab Med, Irvine, CA 92697 USA. EM redwards@uci.edu OI Davis, Jennifer/0000-0001-9456-1682 FU Intramural NIH HHS [Z01 ES101643-05]; NCI NIH HHS [P30 CA062203]; NIDDK NIH HHS [K08 DK059816, R21 DK071591, K08 DK59816] NR 34 TC 4 Z9 5 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD JUL PY 2008 VL 14 IS 7 BP 898 EP 907 DI 10.1002/ibd.20414 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 322UW UT WOS:000257401800004 PM 18340649 ER PT J AU Ahn, SH Shah, YM Inoue, J Morimura, K Kim, I Yim, S Lambert, G Kurotani, R Nagashima, K Gonzalez, FJ Inoue, Y AF Ahn, Sung-Hoon Shah, Yatrik M. Inoue, Junko Morimura, Keiichirou Kim, Insook Yim, SunHee Lambert, Gilles Kurotani, Reiko Nagashima, Kunio Gonzalez, Frank J. Inoue, Yusuke TI Hepatocyte nuclear factor 4 alpha in the intestinal epithelial cells protects against inflammatory bowel disease SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE HNF4 alpha; hepatocyte nuclear factor 4 alpha; intestinal epithelial cell; colitis; nuclear receptors ID ACTIVATED-RECEPTOR-GAMMA; CARCINOMA-ASSOCIATED ANTIGEN; AQUAPORIN WATER CHANNELS; HUMAN MEPRIN-ALPHA; FACTOR-KAPPA-B; ULCERATIVE-COLITIS; GENE-EXPRESSION; FACTOR 4-ALPHA; CROHNS-DISEASE; PPAR-GAMMA AB Background: Hepatocyte nuclear factor 4 alpha (HNF4 alpha; NR2Al) is an orphan member of the nuclear receptor superfamily expressed in liver and intestine. While HNF4 alpha expression is critical for liver function, its role in the gut and in the pathogenesis of inflammatory bowel disease (IBD) is unknown. Methods: Human intestinal biopsies from control and IBD patients were examined for expression of mRNAs encoding HNF4 alpha and other nuclear receptors. An intestine-specific HNF4a null mouse line (Hnf4 alpha(Delta IEpC)) was generated using an Hnf4 alpha-floxed allele and villin-Cre transgene. These mice and their control floxed counter-parts (Hnf4 alpha(F/F)), were subjected to a dextran sulfate sodium (DSS)-induced IBD colitis protocol and their clinical symptoms and gene expression patterns determined. Results: In human intestinal biopsies, HNF4 alpha was significantly decreased in intestinal tissues from Crohn's disease and ulcerative colitis patients. HNF4 alpha expression was also suppressed in the intestine of DSS-treated mice. In Hnf4 alpha(Delta IEpC) mice, disruption of HNF4 alpha expression was observed in the epithelial cells throughout the intestine. In the DSS-induced colitis model Hnf4 alpha(Delta IEpC) mice showed markedly more severe changes in clinical symptoms and pathologies associated with IBD including loss of body weight, colon length, and histological morphology as compared with Hnf4 alpha(F/F) mice. Furthermore, the Hnf4 alpha(Delta IEpC) mice demonstrate a significant alteration of mucin-associated genes and increased intestinal permeability, which may play an important role in the increased susceptibility to acute colitis following an inflammatory insult. Conclusions: While HNF4 alpha does not have a major role in normal function of the intestine, it protects the gut against DSS-induced colitis. C1 [Ahn, Sung-Hoon; Shah, Yatrik M.; Inoue, Junko; Kim, Insook; Yim, SunHee; Kurotani, Reiko; Gonzalez, Frank J.; Inoue, Yusuke] NCI, Lab Metab, Ctr Canc Res, Natl Inst Hlth, Bethesda, MD 20892 USA. [Morimura, Keiichirou] Osaka City Univ, Sch Med, Dept Pathol, Osaka 545, Japan. [Lambert, Gilles] Univ Nantes, INSERM, U539, CHU Hotel Dieu, Nantes, France. [Lambert, Gilles] Heart Res Inst, Camperdown, NSW, Australia. [Kurotani, Reiko] Yokohama City Univ, Cardiovasc Res Inst, Yokohama, Kanagawa, Japan. [Nagashima, Kunio] NCI, Image Anal Lab, Natl Inst Hlth, Frederick, MD 21701 USA. [Inoue, Yusuke] Gunma Univ, Dept Chem & Chem Biol, Grad Sch Engn, Gunma, Japan. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, Natl Inst Hlth, Bldg 37,Room 3106,9000 Rockville Pike, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov FU Intramural NIH HHS [Z01 BC005708-15]; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 75 TC 58 Z9 60 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD JUL PY 2008 VL 14 IS 7 BP 908 EP 920 DI 10.1002/ibd.20413 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 322UW UT WOS:000257401800005 PM 18338782 ER PT J AU Sommers, CL Gurson, JM Surana, R Barda-Saad, M Lee, J Kishor, A Li, W Gasser, AJ Barr, VA Miyaji, M Love, PE Samelson, LE AF Sommers, Connie L. Gurson, Jordan M. Surana, Rishi Barda-Saad, Mira Lee, Jan Kishor, Aparna Li, WenMei Gasser, Adam J. Barr, Valarie A. Miyaji, Michihiko Love, Paul E. Samelson, Lawrence E. TI Bam32: a novel mediator of Erk activation in T cells SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE Erk; IL-4; proliferation; TCR; T lymphocyte ID ANTIGEN RECEPTOR; ADAPTER PROTEIN; PHOSPHATIDYLINOSITOL 3-KINASE; THYMOCYTE SELECTION; TYROSINE RESIDUES; LAT; IDENTIFICATION; DOWNSTREAM; MUTATION; TARGETS AB Bam32 (B lymphocyte adapter molecule of 32 kDa) is an adapter protein expressed in some hematopoietic cells including B and T lymphocytes. It was previously shown that Bam32-deficient mice have defects in various aspects of B cell activation including B cell receptor (BCR)-induced Erk activation, BCR-induced proliferation and T-independent antibody responses. In this study, we have examined the role of Bam32 in T cell activation using Bam32-deficient mice. By comparing CD4(+) T cells from lymph nodes of wild-type and Bam32-deficient mice, we found that Bam32 was required for optimal TCR-induced Erk activation, cytokine production, proliferation and actin-mediated spreading of CD4(+) T cells. These results indicate a novel pathway to Erk activation in T cells involving the adapter protein Bam32. C1 [Sommers, Connie L.; Gurson, Jordan M.; Surana, Rishi; Barda-Saad, Mira; Kishor, Aparna; Li, WenMei; Gasser, Adam J.; Barr, Valarie A.; Miyaji, Michihiko; Samelson, Lawrence E.] Natl Canc Inst, Natl Inst Hlth, Lab Cellular & Mol Biol, Bethesda, MD 20892 USA. [Lee, Jan] US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. [Love, Paul E.] NICHHD, Lab Mammalian Genes & Dev, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Sommers, CL (reprint author), Natl Canc Inst, Natl Inst Hlth, Lab Cellular & Mol Biol, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 CA999999] NR 21 TC 11 Z9 11 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JUL PY 2008 VL 20 IS 7 BP 811 EP 818 DI 10.1093/intimm/dxn039 PG 8 WC Immunology SC Immunology GA 316VT UT WOS:000256978500002 PM 18448454 ER PT J AU Hossain, MZ Yu, Q Xu, M Sen, JM AF Hossain, M. Zulfiquer Yu, Qing Xu, Mai Sen, Jyoti Misra TI ICAT expression disrupts beta-catenin-TCF interactions and impairs survival of thymocytes and activated mature T cells SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE apoptosis; beta-catenin; TCF; ICAT; thymus ID TRANSCRIPTION FACTORS; LINEAGE COMMITMENT; CD28 COSTIMULATION; CADHERIN FUNCTIONS; SELECTION; DIFFERENTIATION; PATHWAY; ANTIGEN; CD8; BCL-X(L) AB T cell factor (TCF) family of transcription factors and beta-catenin critically regulate T cell development as demonstrated by the deletion of the tcf gene, which results in a block early in development that becomes complete in mice bearing tcf/lef double deletion. However, the role of beta-catenin, a major TCF cofactor, remains controversial. To directly address this, we have generated transgenic mice expressing Inhibitor of beta-catenin and TCF (ICAT), a naturally occurring inhibitor that specifically disrupts TCF and beta-catenin interactions. In this report, we demonstrate that disrupting the interaction of beta-catenin with TCF renders adult thymocytes and activated T cells highly susceptible to apoptosis. In contrast to previously reported observations during fetal thymocyte development, these data show that in adult mice, survival and not differentiation of thymocytes, depends on transcription by TCF and beta-catenin. Indeed, we demonstrate that expression of ICAT impedes thymocyte survival by reducing the expression of Bcl(xL) in thymocytes below a critical threshold. Survival of activated mature T cells was also impaired due to diminished expression of activation-induced Bcl(xL). Accordingly, expression of transgenic Bcl-2 rescued activated ICAT-Tg CD4 T cells from apoptosis. Thus, disruption of TCF-beta-catenin interactions specifically impairs the survival of thymocytes and activated T cells. C1 [Hossain, M. Zulfiquer; Yu, Qing; Xu, Mai; Sen, Jyoti Misra] NIA, Lymphocyte Dev Unit, Immunol Lab, Natl Inst Hlth, Baltimore, MD 21224 USA. RP Sen, JM (reprint author), NIA, Lymphocyte Dev Unit, Immunol Lab, Natl Inst Hlth, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM Jyoti-Sen@NIH.GOV FU Intramural NIH HHS [Z01 AG000768-04] NR 36 TC 15 Z9 15 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JUL PY 2008 VL 20 IS 7 BP 925 EP 935 DI 10.1093/intimm/dxn051 PG 11 WC Immunology SC Immunology GA 316VT UT WOS:000256978500013 PM 18511409 ER PT J AU Engels, EA Biggar, RJ Hall, HI Cross, H Crutchfield, A Finch, JL Griggs, R Hylton, T Pawlish, KS McNeel, TS Goedert, JJ AF Engels, Eric A. Biggar, Robert J. Hall, H. Irene Cross, Helene Crutchfield, Allison Finch, Jack L. Griggs, Rebecca Hylton, Tara Pawlish, Karen S. McNeel, Timothy S. Goedert, James J. TI Cancer risk in people infected with human immunodeficiency virus in the United States SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE HIV/AIDS; epidemiology; Kaposi sarcoma; non-Hodgkin lymphoma; Hodgkin lymphoma; liver cancer; lung cancer ID ACTIVE ANTIRETROVIRAL THERAPY; SQUAMOUS INTRAEPITHELIAL LESIONS; AIDS-DEFINING CANCERS; HUMAN-PAPILLOMAVIRUS; HEPATOCELLULAR-CARCINOMA; HODGKIN-LYMPHOMA; HIV-INFECTION; LUNG-CANCER; PREVALENCE; COHORT AB Data are limited regarding cancer risk in human immunodeficiency virus (HIV)-infected persons with modest immunosuppres. sion, before the onset of acquired immunodeficiency syndrome (AIDS). For some cancers, risk may be affected by highly active antiretroviral therapy (HAART) widely available since 1996. We linked HIV/AIDS and cancer registries in Colorado, Florida and New Jersey. Standardized incidence ratios (SIRs) compared cancer risk in HIV-infected persons (initially AIDS-free) during the 5-year period after registration with the general population. Poisson regression was used to compare incidence across subgroups, adjusting for demographic factors. Among 57,350 HIV-infected persons registered during 1991-2002 (median CD4 count 491 cells/mm(3)), 871 cancers occurred during follow-up. Risk was elevated for Kaposi sarcoma (KS, SIR 1,300 [n = 173 cases]), non-Hodgkin lymphoma (NHL, 7.3 [n = 203]), cervical cancer (2.9 [n = 28]) and several non-AIDS-defining malignancies, including Hodgkin lymphoma (5.6 [n = 36]) and cancers of the lung (2.6 [n = 109]) and liver (2.7 [n = 14]). KS and NHL incidence declined over time but nonetheless remained elevated in 1996-2002. Incidence increased in 1996-2002 compared to 1991-1995 for Hodgkin lymphoma (relative risk 2.7, 95%CI 1.0-7.1) and liver cancer (relative risk infinite, one-sided 95%CI 1.1-infinity). Non-AIDS-defining cancers comprised 31.4% of cancers in 1991-1995, versus 58.0% in 1996-2002. For KS and NHL, risk was inversely related to CD4 count, but these associations attenuated after 1996. We conclude that KS and NHL incidence declined markedly in recent years, likely reflecting HAART-related improvements in immunity, while incidence of some non-AIDS-defining cancers increased. These trends have led to a shift in the spectrum of cancer among HIV-infected persons. (C) 2008 Wiley-Liss, Inc. C1 [Engels, Eric A.; Biggar, Robert J.; Goedert, James J.] NCI, Div Canc Epidemiol & Genet, Infect Immunoepidemiol Branch, Rockville, MD 20852 USA. [Hall, H. Irene] Ctr Dis Control & Prevent, Atlanta, GA USA. [Cross, Helene] New Jersey Dept Hlth & Senior Serv, Trenton, NJ USA. [Crutchfield, Allison; Finch, Jack L.] Colorado Dept Publ Hlth, Denver, CO USA. [Griggs, Rebecca; Hylton, Tara] Florida Dept Hlth, Tallahassee, FL USA. [McNeel, Timothy S.] Informat Management Serv Incorp, Silver Spring, MD USA. RP Engels, EA (reprint author), NCI, Div Canc Epidemiol & Genet, Infect Immunoepidemiol Branch, 6120 Execut Blvd,EPS 7076, Rockville, MD 20852 USA. EM engelse@exchange.nih.gov FU Intramural NIH HHS NR 40 TC 344 Z9 347 U1 1 U2 11 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 1 PY 2008 VL 123 IS 1 BP 187 EP 194 DI 10.1002/ijc.23487 PG 8 WC Oncology SC Oncology GA 302MU UT WOS:000255973200025 PM 18435450 ER PT J AU Sherman, ME Ronnett, BM Ioffe, OB Richesson, DA Rush, BB Glass, AG Chatterjee, N Duggan, MA Lacey, JV AF Sherman, Mark E. Ronnett, Brigitte M. Ioffe, Olga B. Richesson, Douglas A. Rush, Brenda B. Glass, Andrew G. Chatterjee, Nilanjan Duggan, Maire A. Lacey, James V., Jr. TI Reproducibility of biopsy diagnoses of endometrial hyperplasia: Evidence supporting a simplified classification SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE Endometrium; reproducibility; diagnosis; hyperplasia; WHO ID GYNECOLOGIC-ONCOLOGY-GROUP; CARCINOMA; NEOPLASIA; WOMEN AB Background: Identifying which categories in the World Health Organization classification of endometrial hyperplasia contribute to suboptimal reproducibility is clinically important. Methods: A 2-member panel reviewed 209 endometrial biopsy/curettage specimens originally diagnosed as incident endometrial hyperplasia as part of a progression study. Original diagnoses included the following: disordered proliferative endometrium, simple hyperplasia, complex hyperplasia, and atypical hyperplasia; panel diagnoses also included negative and carcinoma. We assessed percentage agreement and kappa statistics +/- standard errors (K +/- SE). Results: Original and panel diagnoses (combining negative with disordered proliferative endometrium; atypical hyperplasia with carcinoma) agreed for 34.9% of biopsies (K-unweighted +/- SE=0.18 +/- 0.03; K-weighted +/- SE=0.27+0.04). Panelists' diagnoses agreed (using 6 categories) for 51.7% of biopsies, corresponding to K-unweighted +/- SE=0.37 +/- 0.03, improving with weighting to K-weighted +/- SE = 0.63 +/- 0.05. Reproducibility based on a 2-tier classification ([negative, disordered proliferative endometrium, simple hyperplasia, or complex hyperplasia] versus [atypical hyperplasia or carcinoma]) increased agreement between original and panel diagnoses to 82.8%, K-unweighted +/- SE=0.37 +/- 0.06, and between panelists to 87.0%, K-unweighted +/- SE=0.63 +/- 0.07. Agreement between panelists at a cutpoint of complex hyperplasia and more severe versus simple hyperplasia or less severe was 88.0%, K-unweighted +/- SE=0.72 +/- 0.07. Conclusions: Developing and prospectively testing a binary system of classifying endometrial hyperplasia on endometrial biopsy may aid efforts to improve interobserver reproducibility. C1 [Sherman, Mark E.; Richesson, Douglas A.; Chatterjee, Nilanjan] Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. [Ronnett, Brigitte M.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Ioffe, Olga B.] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD USA. [Rush, Brenda B.; Glass, Andrew G.] Kaiser Permanente Ctr Hlth Res, Portland, OR USA. [Duggan, Maire A.] Univ Calgary, Dept Pathol, Calgary, AB, Canada. [Duggan, Maire A.] Univ Calgary, Lab Med, Calgary, AB, Canada. RP Sherman, ME (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 5028, Rockville, MD 20892 USA. EM shermanm@mail.nih.gov FU Intramural NIH HHS NR 15 TC 21 Z9 26 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JUL PY 2008 VL 27 IS 3 BP 318 EP 325 DI 10.1097/PGP.0b013e3181659167 PG 8 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 321BA UT WOS:000257277900002 PM 18580308 ER PT J AU Shen, M Vermeulen, R Chapman, RS Berndt, SI He, XZ Chanock, S Caporaso, N Lan, Q AF Shen, Min Vermeulen, Roel Chapman, Robert S. Berndt, Sonja I. He, Xingzhou Chanock, Stephen Caporaso, Neil Lan, Qing TI A report of cytokine polymorphisms and COPD risk in Xuan Wei, China SO INTERNATIONAL JOURNAL OF HYGIENE AND ENVIRONMENTAL HEALTH LA English DT Article DE COPD; cytokine; CSF2; IL8; single nucleotide polymorphism; indoor air pollution ID OBSTRUCTIVE PULMONARY-DISEASE; SYNCYTIAL VIRUS BRONCHIOLITIS; GM-CSF; AIR-POLLUTION; LUNG-CANCER; ASTHMA; ASSOCIATION; IMPROVEMENT; GENE; IL8 AB Indoor air pollution has been documented as an important risk factor for chronic obstructive pulmonary disease (COPD), and inflammation is central to the development and progression of COPD. Single nucleotide polymorphisms (SNP) in some cytokine genes have been reported to be associated with COPD. We examined the association between 18 SNPs in 10 cytokine genes and COPD risk in a case-control study conducted in a population with high exposure to indoor smoky coal emissions. The study included 53 COPD cases and 122 healthy community controls. Carriers of the CSF2 117Ile allele had a 2.4-fold higher risk of COPD than the wild type (Thr/Thr) carriers (OR: 2.44; 95% CI: 1.10-5.41), and the AA genotype at IL8-351 was associated with an increased risk of COPD (OR: 2.71; 95% CI: 1.04-7.04). When the combined effects of CSF2 117Ile and IL8-351A were examined, individuals carrying at least one variant in both genes had a five-fold increased risk of COPD (OR: 5.14, 95% CI: 1.32-29.86). This study suggests that polymorphisms in both CSF2 and IL8 may play a role in the pathogenesis of COPD, at least in highly exposed populations. However, in view of our relatively small sample size, this study should be replicated in other populations with substantial exposure to indoor air pollutants such as polycyclic aromatic hydrocarbons (PAH) and particulate matter. (C) 2007 Elsevier GmbH. All rights reserved. C1 [Shen, Min; Vermeulen, Roel; Berndt, Sonja I.; Lan, Qing] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. [Vermeulen, Roel] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands. [Vermeulen, Roel] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [Chapman, Robert S.] Chulalongkorn Univ, Coll Publ Hlth, Bangkok, Thailand. [He, Xingzhou] Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China. [Chanock, Stephen] NCI, Core Genotyping Facil, NIH, DHHS, Bethesda, MD 20892 USA. [Caporaso, Neil] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. RP Shen, M (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, MSC 7240,6120 Execut Blvd, Bethesda, MD 20892 USA. EM shenmi@mail.nih.gov RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 FU Intramural NIH HHS [NIH0011547510]; PHS HHS [NIH0011547510] NR 16 TC 11 Z9 13 U1 1 U2 3 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 1438-4639 J9 INT J HYG ENVIR HEAL JI Int. J. Hyg. Environ. Health. PD JUL PY 2008 VL 211 IS 3-4 BP 352 EP 356 DI 10.1016/j.ijheh.2007.05.002 PG 5 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 333VJ UT WOS:000258180600016 PM 17681858 ER PT J AU Detera-Wadleigh, S AF Detera-Wadleigh, S. TI Making sense of candidate susceptibility genes for mood disorders front whole genome association studies SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 26th Collegium Internationale Neuro-Psychopharmacologicum Congress (CINP) CY JUL 13-17, 2008 CL Munich, GERMANY C1 [Detera-Wadleigh, S.] NIMH, Lab Mol Psychiat, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 JUL PY 2008 VL 11 SU 1 BP 8 EP 8 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 343LO UT WOS:000258855500032 ER PT J AU Manji, HK Chen, G Salvadore, G Duncan, W Du, J Zarate, C AF Manji, H. K. Chen, G. Salvadore, G. Duncan, W. Du, J. Zarate, C. TI Targeting remission: Strategies to enhance the therapeutic efficacy of antidepressants SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 26th Collegium Internationale Neuro-Psychopharmacologicum Congress (CINP) CY JUL 13-17, 2008 CL Munich, GERMANY C1 [Manji, H. K.; Chen, G.; Salvadore, G.; Duncan, W.; Du, J.; Zarate, C.] NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. RI Chen, Guang/A-2570-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 2008 VL 11 SU 1 BP 9 EP 9 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 343LO UT WOS:000258855500038 ER PT J AU Drevets, W AF Drevets, W. TI Neuroplasticity, neuroimaging and depression SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 26th Collegium Internationale Neuro-Psychopharmacologicum Congress (CINP) CY JUL 13-17, 2008 CL Munich, GERMANY C1 [Drevets, W.] NIMH, Mood & Anxiety Disorder, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 JUL PY 2008 VL 11 SU 1 BP 41 EP 41 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 343LO UT WOS:000258855500174 ER PT J AU Gould, T Kovacsics, C O'Donnell, K Dow, E Du, J Chen, G Manji, HK AF Gould, T. Kovacsics, C. O'Donnell, K. Dow, E. Du, J. Chen, G. Manji, H. K. TI Behavioral effects of Lithium in rodent models: Important leads for the development of novel therapeutics SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 26th Collegium Internationale Neuro-Psychopharmacologicum Congress (CINP) CY JUL 13-17, 2008 CL Munich, GERMANY C1 [Gould, T.] Univ Maryland, Sch Med Psychiat, Elkridge, MD USA. [Kovacsics, C.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [O'Donnell, K.; Dow, E.; Du, J.; Chen, G.; Manji, H. K.] NIMH, NIH, Bethesda, MD 20892 USA. RI Chen, Guang/A-2570-2017 NR 0 TC 0 Z9 0 U1 0 U2 2 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 JUL PY 2008 VL 11 SU 1 BP 49 EP 49 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 343LO UT WOS:000258855500210 ER PT J AU Holmes, A AF Holmes, A. TI Genetic modulation of fronto-amygdala morphology and function in mice SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 26th Collegium Internationale Neuro-Psychopharmacologicum Congress (CINP) CY JUL 13-17, 2008 CL Munich, GERMANY C1 [Holmes, A.] NIAAA, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 2008 VL 11 SU 1 BP 57 EP 57 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 343LO UT WOS:000258855500242 ER PT J AU Volkow, N AF Volkow, N. TI Dopaminergic activity in caudate of ADHD patients SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 26th Collegium Internationale Neuro-Psychopharmacologicum Congress (CINP) CY JUL 13-17, 2008 CL Munich, GERMANY C1 [Volkow, N.] Natl Inst Drug Abuse, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 JUL PY 2008 VL 11 SU 1 BP 57 EP 57 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 343LO UT WOS:000258855500243 ER PT J AU Zarate, C AF Zarate, C. TI Glutamatergic system based treatments in mood disorders SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 26th Collegium Internationale Neuro-Psychopharmacologicum Congress (CINP) CY JUL 13-17, 2008 CL Munich, GERMANY C1 [Zarate, C.] NIMH, Dept Psychiat, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 2008 VL 11 SU 1 BP 62 EP 62 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 343LO UT WOS:000258855500266 ER PT J AU Manji, HK Du, J Wei, Y Machado-Vieira, R Malkesman, O Chen, G Wang, Y AF Manji, H. K. Du, J. Wei, Y. Machado-Vieira, R. Malkesman, O. Chen, G. Wang, Y. TI GSK-3b kinase modulates AMPA mediated synaptic and behavioral plasticity: A new approach for GSK-3b specific drugs SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 26th Collegium Internationale Neuro-Psychopharmacologicum Congress (CINP) CY JUL 13-17, 2008 CL Munich, GERMANY C1 [Manji, H. K.; Du, J.; Wei, Y.; Machado-Vieira, R.; Malkesman, O.; Chen, G.; Wang, Y.] NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. RI MACHADO-VIEIRA, RODRIGO/D-8293-2012; Chen, Guang/A-2570-2017 OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190; NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 2008 VL 11 SU 1 BP 75 EP 75 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 343LO UT WOS:000258855500326 ER PT J AU Heilig, M Ciccocioppo, R Cippitelli, A Thorsell, A Sommer, W Hansson, A Rimondini, R AF Heilig, M. Ciccocioppo, R. Cippitelli, A. Thorsell, A. Sommer, W. Hansson, A. Rimondini, R. TI Convergence of genetic and environmental models of high alcohol preference identifies a key role for the CRH system SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 26th Collegium Internationale Neuro-Psychopharmacologicum Congress (CINP) CY JUL 13-17, 2008 CL Munich, GERMANY C1 [Heilig, M.] NIAAA, NIH, Lab Clin & Translat Studies, Bethesda, MD USA. RI Rimondini, Roberto/B-2500-2010 OI Rimondini, Roberto/0000-0003-4099-513X NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 2008 VL 11 SU 1 BP 80 EP 80 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 343LO UT WOS:000258855500347 ER PT J AU Hasler, G Fromm, S Carlson, PJ Luckenbaugh, DA Waldeck, T Geraci, M Roiser, J Neumeister, A Meyers, N Charrney, DS Drevets, W AF Hasler, G. Fromm, S. Carlson, P. J. Luckenbaugh, D. A. Waldeck, T. Geraci, M. Roiser, J. Neumeister, A. Meyers, N. Charrney, D. S. Drevets, W. TI Dysfunction of the catecholaminergic system as a trait abnormality in major depression SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 26th Collegium Internationale Neuro-Psychopharmacologicum Congress (CINP) CY JUL 13-17, 2008 CL Munich, GERMANY C1 [Hasler, G.] Univ Zurich Hosp, Dept Psychiat, CH-8091 Zurich, Switzerland. [Fromm, S.; Carlson, P. J.; Luckenbaugh, D. A.; Waldeck, T.; Geraci, M.; Roiser, J.] Inst Cognit Neurosci, London, England. [Neumeister, A.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Meyers, N.; Charrney, D. S.; Drevets, W.] NIMH, Bethesda, MD 20892 USA. RI Hasler, Gregor/E-4845-2012 OI Hasler, Gregor/0000-0002-8311-0138 NR 0 TC 0 Z9 0 U1 0 U2 1 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 JUL PY 2008 VL 11 SU 1 BP 96 EP 96 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 343LO UT WOS:000258855500402 ER PT J AU Hayashi, T Su, TP AF Hayashi, T. Su, T. -P. TI A novel molecular chaperone sigma-1 receptor: Potential therapeutic target for neuropsychiatric disorders SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 26th Collegium Internationale Neuro-Psychopharmacologicum Congress (CINP) CY JUL 13-17, 2008 CL Munich, GERMANY C1 [Hayashi, T.; Su, T. -P.] NIDA, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 1 U1 0 U2 1 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 JUL PY 2008 VL 11 SU 1 BP 116 EP 117 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 343LO UT WOS:000258855500482 ER PT J AU Schloesser, R Lednak, JB Chen, G Manji, HK AF Schloesser, R. Lednak, J. -B. Chen, G. Manji, H. K. TI Adult neurogenesis in heterozygous bcl-2 KO mice SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 26th Collegium Internationale Neuro-Psychopharmacologicum Congress (CINP) CY JUL 13-17, 2008 CL Munich, GERMANY C1 [Schloesser, R.; Lednak, J. -B.; Chen, G.; Manji, H. K.] NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. RI Chen, Guang/A-2570-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 2008 VL 11 SU 1 BP 132 EP 132 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 343LO UT WOS:000258855500545 ER PT J AU Mueller, S Maheu, E Dozier, M Peloso, E Mandell, D Leibenluft, E Pine, D Ernst, M AF Mueller, S. Maheu, E. Dozier, M. Peloso, E. Mandell, D. Leibenluft, E. Pine, D. Ernst, M. TI Early life stress due to maltreatment in childhood alters inhibitory motor control: an fMRI study SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 26th Collegium Internationale Neuro-Psychopharmacologicum Congress (CINP) CY JUL 13-17, 2008 CL Munich, GERMANY C1 [Mueller, S.; Maheu, E.; Mandell, D.; Leibenluft, E.; Pine, D.; Ernst, M.] NIMH, NIH, EDAN, MAP, Bethesda, MD 20892 USA. [Dozier, M.; Peloso, E.] Univ Delaware, Newark, DE USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 JUL PY 2008 VL 11 SU 1 BP 223 EP 224 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 343LO UT WOS:000258855501209 ER PT J AU Grunblatt, E Hall, SF Kreutzfeldt, M Perona, MT Nietzer, S Sora, I Uhl, GR Riederer, R Lesch, KP Gerlach, M Schmitt, AG AF Gruenblatt, E. Hall, S. F. Kreutzfeldt, M. Perona, M. T. Nietzer, S. Sora, I. Uhl, G. R. Riederer, R. Lesch, K. -P. Gerlach, M. Schmitt, A. G. TI Methylphenidate and stress exert influences on synaptic protein expression in a mouse model for attention-deficit/hyperactivity disorder SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 26th Collegium Internationale Neuro-Psychopharmacologicum Congress (CINP) CY JUL 13-17, 2008 CL Munich, GERMANY C1 [Gruenblatt, E.; Kreutzfeldt, M.; Nietzer, S.; Riederer, R.; Lesch, K. -P.; Schmitt, A. G.] Univ Wurzburg, Psychiat Clin, D-97070 Wurzburg, Germany. [Hall, S. F.; Perona, M. T.; Uhl, G. R.] NIDA, Mol Neurobiol Branch, Baltimore, MD USA. [Sora, I.] Tohoku Univ, Dept Neurosci, Sendai, Miyagi 980, Japan. RI Grunblatt, Edna/A-6762-2016 OI Grunblatt, Edna/0000-0001-8505-7265 NR 0 TC 0 Z9 0 U1 0 U2 1 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 JUL PY 2008 VL 11 SU 1 BP 232 EP 232 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 343LO UT WOS:000258855501244 ER PT J AU Wultsch, T Popp, S Lesch, KP Wess, J Reif, A AF Wultsch, T. Popp, S. Lesch, K. -P Wess, J. Reif, A. TI Behavioral phenotyping of M1 muscarinic acetylcholine receptor-knockout mice SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 26th Collegium Internationale Neuro-Psychopharmacologicum Congress (CINP) CY JUL 13-17, 2008 CL Munich, GERMANY C1 [Wultsch, T.; Popp, S.; Lesch, K. -P] Univ Wurzburg, Dept Psychiat, Wurzburg, Germany. [Wess, J.] Natl Inst Hlth, Mol Signaling Sect, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 JUL PY 2008 VL 11 SU 1 BP 232 EP 232 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 343LO UT WOS:000258855501247 ER PT J AU Yamamoto, T Hiranita, T Nawata, Y Kagamiishi, Y AF Yamamoto, T. Hiranita, T. Nawata, Y. Kagamiishi, Y. TI The role of corticotropin-releasing factor in cue- and methamphetamine-induced reinstatement of methamphetamine-seeking in rats SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 26th Collegium Internationale Neuro-Psychopharmacologicum Congress (CINP) CY JUL 13-17, 2008 CL Munich, GERMANY C1 [Yamamoto, T.; Nawata, Y.] Nagasaki Int Univ, Sasebo, Japan. [Hiranita, T.] NIDA, NIH, Baltimore, MD USA. [Kagamiishi, Y.] ONO Pharmaceut Co Ltd, Osaka, Japan. RI Hiranita, Takato/G-6567-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 2008 VL 11 SU 1 BP 235 EP 235 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 343LO UT WOS:000258855501256 ER PT J AU Su, TP Tsai, SY Hayashi, T AF Su, T. -P. Tsai, S. -Y. Hayashi, T. TI Sigma-1 receptor chaperones at the ER regulate dendritic arborization and NMDA/AMPA receptor anchorings in primary hippocampal neurons SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 26th Collegium Internationale Neuro-Psychopharmacologicum Congress (CINP) CY JUL 13-17, 2008 CL Munich, GERMANY C1 [Su, T. -P.; Tsai, S. -Y.; Hayashi, T.] NIDA, NIH, Cellular Pathobiol Sect, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 3 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 JUL PY 2008 VL 11 SU 1 BP 237 EP 238 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 343LO UT WOS:000258855501266 ER PT J AU Mueller, S Temple, V Pinc, D Ernst, M AF Mueller, S. Temple, V. Pinc, D. Ernst, M. TI Perturbed spatial processing in pediatric anxiety in a virtual water maze task SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 26th Collegium Internationale Neuro-Psychopharmacologicum Congress (CINP) CY JUL 13-17, 2008 CL Munich, GERMANY C1 [Mueller, S.; Temple, V.; Pinc, D.; Ernst, M.] NIMH, NIH, MAP, EDAN, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 2008 VL 11 SU 1 BP 274 EP 274 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 343LO UT WOS:000258855501413 ER PT J AU Zhang, X Shu, XO Chow, WH Yang, G Li, H Gao, J Gao, YT Zheng, W AF Zhang, X. Shu, X-O Chow, W-H Yang, G. Li, H. Gao, J. Gao, Y-T Zheng, W. TI Body mass index at various ages and mortality in Chinese women: impact of potential methodological biases SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE body mass index; epidemiology; mortality; methodological bias ID LONGITUDINAL FOLLOW-UP; PROSPECTIVE COHORT; PHYSICAL-ACTIVITY; EXCESS DEATHS; OBESITY; WEIGHT; OVERWEIGHT; HEALTH; MEN; ADIPOSITY AB Background: Inadequate control for potential methodological biases has been suggested as an explanation for the conflicting findings concerning the relationship between body mass index (BMI) and mortality. Methods: Using data from the Shanghai Women's Health Study, a prospective cohort study conducted in a relatively lean population, we examined the associations of BMI at various ages and average adult BMI with mortality and evaluated the impact of potential biases related to preexisting illness and cigarette smoking on the associations. Included in the analysis were 74 896 women aged 40-70 years with anthropometrics taken by trained interviewers at baseline (1996-2000). Recalled body sizes at ages 20 and 50 years were also obtained for older women. Participants were followed through April 2007 by biennial home visits and linkage with the vital statistics registry. Results: During a mean follow-up of 7.4 years, 2389 deaths occurred. In initial analyses, both low and high levels of baseline BMI were associated with an increase in mortality, whereas mortality increased monotonically with increasing levels of average adult BMI, BMI at the age of 50 years and, to a lesser extent, BMI at the age of 20 years. A direct monotonic relationship between baseline BMI and mortality emerged after accounting for potential biases. Controlling for potential biases also strengthened the positive associations of average adult BMI and BMI at ages 20 and 50 years with mortality, with a hazard ratio comparing the highest vs the lowest quartiles of average adult BMI reaching 2.19 (95% CI, 1.67-2.88). Conclusion: High BMI during adulthood consistently predicts mortality risk after accounting for potential biases. C1 [Zhang, X.; Shu, X-O; Yang, G.; Zheng, W.] Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Inst Med & Publ Hlth,Dept Med, Med Ctr,Sch Med, Nashville, TN 37203 USA. [Chow, W-H] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Li, H.; Gao, J.; Gao, Y-T] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. RP Zhang, X (reprint author), Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Inst Med & Publ Hlth,Dept Med, Med Ctr,Sch Med, 6th Floor,Suite 600,2525 W End Ave, Nashville, TN 37203 USA. EM xianglan.zhang@vanderbilt.edu FU NCI NIH HHS [R01 CA070867-11, R01 CA070867, R01CA70867]; NHLBI NIH HHS [R01HL079123, R01 HL079123, R01 HL079123-03]; NICHD NIH HHS [K12 HD043483, 2K12HD043483-06, K12 HD043483-06] NR 29 TC 7 Z9 7 U1 1 U2 3 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 JUL PY 2008 VL 32 IS 7 BP 1130 EP 1136 DI 10.1038/ijo.2008.63 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 325SA UT WOS:000257607400013 PM 18461072 ER PT J AU Thanos, PK Michaelides, M Gispert, JD Pascau, J Soto-Montenegro, ML Desco, M Wang, R Wang, GJ Volkow, ND AF Thanos, P. K. Michaelides, M. Gispert, J-D Pascau, J. Soto-Montenegro, M. L. Desco, M. Wang, R. Wang, G-J Volkow, N. D. TI Differences in response to food stimuli in a rat model of obesity: in-vivo assessment of brain glucose metabolism SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE (18)FDG-craving-Zucker-food restriction; ingestive behavior; positron emission tomography-hippocampus ID LONG-TERM POTENTIATION; SPATIAL MEMORY; LEPTIN; HIPPOCAMPUS; INSULIN; CORTEX; IMPAIRMENT; CIRCUITRY; BEHAVIOR; IMPACT AB Objective: Food intake is regulated by factors that modulate caloric requirements as well as food's reinforcing properties. In this study, we measured brain glucose utilization to an olfactory stimulus (bacon scent), and we examined the role of food restriction and genetic predisposition to obesity on such brain metabolic activity. Methods: Zucker obese (Ob) and lean (Le) rats were divided into four groups: (1) Ob ad-libitum fed, (2) Ob food restricted (70% of ad libitum), (3) Le ad-libitum fed and (4) Le food restricted. Rats were scanned using m-positron emission tomography and 2-[(18)F]-fluoro- 2-deoxy-D-glucose under two conditions: (1) baseline scan (no stimulation) and (2) challenge scan (food stimulation, FS). Results: FS resulted in deactivation of the right and left hippocampus. Ob rats showed greater changes with FS than Le rats (deactivation of hippocampus and activation of the medial thalamus) and Ob but not Le animals deactivated the frontal cortex and activated the superior colliculus. Access to food resulted in an opposite pattern of metabolic changes to the food stimuli in olfactory nucleus (deactivated in unrestricted and activated in restricted) and in right insular/parietal cortex (activated in unrestricted and deactivated in restricted). In addition, restricted but not unrestricted animals activated the medial thalamus. Conclusions: The greater changes in the Ob rats suggest that leptin modulates the regional brain responses to a familiar food stimulus. Similarly, the differences in the pattern of responses with food restriction suggest that FS is influenced by access to food conditions. The main changes with FS occurred in the hippocampus, a region involved in memory, the insular cortex, a region involved with interoception (perception of internal sensations), the medial thalamus (region involved in alertness) and in regions involved with sensory perception (olfactory bulb, olfactory nucleus, occipital cortex, superior colliculus and parietal cortex), which corroborates their relevance in the perception of food. C1 [Thanos, P. K.; Michaelides, M.; Wang, R.; Wang, G-J] Brookhaven Natl Lab, Dept Med, Behav Neuropharmacol & Neuroimaging Lab, Upton, NY 11973 USA. [Thanos, P. K.; Michaelides, M.; Volkow, N. D.] NIAAA, Lab Neuroimaging, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD USA. [Thanos, P. K.; Michaelides, M.] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. [Gispert, J-D] Inst Alta Tecnol Parc Rec Biomed Barcelona, Barcelona, Spain. [Pascau, J.; Soto-Montenegro, M. L.; Desco, M.] Univ Gregorio Maranon, Unidad Med & Cirugia Expt, Gen Hosp, Madrid, Spain. RP Thanos, PK (reprint author), Brookhaven Natl Lab, Dept Med, Behav Neuropharmacol & Neuroimaging Lab, 30 Bell Ave, Upton, NY 11973 USA. EM thanos@bnl.gov RI Pascau, Javier/B-5734-2013; Desco, Manuel/D-2822-2009; OI Pascau, Javier/0000-0003-1484-731X; Desco, Manuel/0000-0003-0989-3231; Gispert, Juan Domingo/0000-0002-6155-0642 FU Intramural NIH HHS [Z01 AA000551-04]; NIAAA NIH HHS [P50 AA007611, R01 AA011034, T32 AA007574] NR 40 TC 23 Z9 23 U1 1 U2 3 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 JUL PY 2008 VL 32 IS 7 BP 1171 EP 1179 DI 10.1038/ijo.2008.50 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 325SA UT WOS:000257607400018 PM 18475275 ER PT J AU Ward, MH Heineman, EF Markin, RS Weisenburger, DD AF Ward, Mary H. Heineman, Ellen F. Markin, Rodney S. Weisenburger, Dennis D. TI Adenocarcinoma of the stomach and esophagus and drinking water and dietary sources of nitrate and nitrite SO INTERNATIONAL JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH LA English DT Article DE nitrate; nitrite; stomach cancer; esophagus cancer; diet; drinking water ID N-NITROSO COMPOUNDS; GASTRIC-CANCER; NUTRIENT INTAKE; RISK; EXPOSURE; MEAT AB We conducted a population-based case-control study of adenocarcinoma of the stomach and esophagus in Nebraska, U.S.A. Nitrate concentrations in public drinking water supplies were linked to residential water source histories. Among those using private wells at the time of the interview, we measured nitrate levels in water samples from wells. Dietary nitrate and nitrite were estimated from a food-frequency questionnaire. Among those who primarily used public water supplies (79 distal stomach, 84 esophagus, 321 controls), average nitrate levels were not associated with risk (highest versus lowest quartile: stomach OR=1.2, 95% CI [0.5-2.7]; esophagus OR=1.3, 95% CI [0.6-3.1]). We observed the highest ORs for distal stomach cancer among those with higher water nitrate ingestion and higher intake of processed meat compared with low intakes of both; however, the test for positive interaction was not significant (p=0.213). We did not observe this pattern for esophagus cancer. Increasing intake of nitrate and nitrite from animal sources was associated with elevated ORs for stomach cancer and with a significant positive trend in risk of esophagus cancer (P-trend =0.325 and 0.015, respectively). Larger studies with higher exposures to drinking water sources of nitrate are warranted to further evaluate N-nitroso compound precursors as risk factors for these cancers. C1 [Ward, Mary H.; Heineman, Ellen F.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Markin, Rodney S.; Weisenburger, Dennis D.] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA. RP Ward, MH (reprint author), NCI, Occupat & Environ Epidemiol Branch, 6120 Executive Blvd EPS-8006, Bethesda, MD 20892 USA. EM wardm@mail.nih.gov FU Intramural NIH HHS [Z01 CP010125-12] NR 24 TC 23 Z9 24 U1 0 U2 4 PU ABEL PUBLICATION SERVICES PI BURLINGTON PA 1611 AQUINAS COURT, BURLINGTON, NC 27215 USA SN 1077-3525 J9 INT J OCCUP ENV HEAL JI Int. J. Occup. Environ. Health PD JUL-SEP PY 2008 VL 14 IS 3 BP 193 EP 197 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 330XE UT WOS:000257975300005 PM 18686719 ER PT J AU Goldin, E Caruso, RC Benko, W Kaneski, CR Stahl, S Schiffmann, R AF Goldin, Ehud Caruso, Rafael C. Benko, William Kaneski, Christine R. Stahl, Stephanie Schiffmann, Raphael TI Isolated ocular disease is associated with decreased mucolipin-1 channel conductance SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID CATION CHANNEL; IV; IDENTIFICATION; MUTATIONS; PROTEIN; VARIANT; PH AB PURPOSE. To evaluate a 15-year-old boy with MLIV (mucolipidosis type IV) and clinical abnormalities restricted to the eye who also had achlorhydria with elevated blood gastrin levels. METHODS. In addition to a detailed neuro-ophthalmic and electrophysiological assessment, his mutant mucolipin-1 was experimentally expressed in liposomes and its channel properties studied in vitro. RESULTS. The patient was a compound heterzygote for c. 920delT and c. 1615delG. Detailed neuro-ophthalmic examination including electroretinography showed him to have a typical retinal dystrophy predominantly affecting rod and bipolar cell function. In vitro expression of MCOLN1 in liposomes showed that the c. 1615delG mutated channel had significantly reduced conductance compared with wild-type mucolipin-1, whereas the inhibitory effect of low pH and amiloride remained intact. CONCLUSIONS. These findings suggest that reduced channel conductance is relatively well tolerated by the brain during development, whereas retinal cells and stomach parietal cells require normal protein function. MLIV should be considered in patients with retinal dystrophy of unknown cause and screened for using blood gastrin levels. C1 [Goldin, Ehud] NHGRI, Med Genet Branch, Mol Neurogenet Sect, Bethesda, MD 20892 USA. [Caruso, Rafael C.] NEI, Ophthalm Genet & Visual Funct Branch, Bethesda, MD 20892 USA. [Benko, William; Kaneski, Christine R.; Stahl, Stephanie; Schiffmann, Raphael] Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branch, NIH, Bethesda, MD USA. RP Schiffmann, R (reprint author), Baylor Res Inst, Inst Metab Dis, 3812 Elm St, Dallas, TX 75226 USA. EM raphael.schiffmann@baylorhealth.edu OI Kaneski, Christine/0000-0003-1453-2502 FU Intramural NIH HHS [Z99 HG999999, , Z01 NS002984-09] NR 19 TC 6 Z9 6 U1 0 U2 0 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 JUL PY 2008 VL 49 IS 7 BP 3134 EP 3142 DI 10.1167/iovs.07-1649 PG 9 WC Ophthalmology SC Ophthalmology GA 318WR UT WOS:000257124000046 PM 18326692 ER PT J AU Young, A Powelson, EB Whitney, IE Raven, MA Nusinowitz, S Jiang, MS Birnbaumer, L Reese, BE Farber, DB AF Young, Alejandra Powelson, Elisabeth B. Whitney, Irene E. Raven, Mary A. Nusinowitz, Steven Jiang, Meisheng Birnbaumer, Lutz Reese, Benjamin E. Farber, Debora B. TI Involvement of OA1, an intracellular GPCR, and G alpha i3, its binding protein, in melanosomal biogenesis and optic pathway formation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID LINKED OCULAR ALBINISM; RETINAL-PIGMENT; GAP-JUNCTIONS; INBRED MICE; GENE; PROJECTIONS; LATERALITY; EPITHELIUM; TYPE-1; FAMILY AB PURPOSE. Ocular albinism type 1 ( OA1) is characterized by abnormalities in retinal pigment epithelium ( RPE) melanosomes and misrouting of optic axons. The OA1 gene encodes a G-protein-coupled receptor ( GPCR) that coimmunoprecipitates with the G alpha i- subunit of heterotrimeric G-proteins from human melanocyte extracts. This study was undertaken to test whether one of the G alpha i proteins, G alpha i3, signals in the same pathway as OA1 to regulate melanosome biogenesis and axonal growth through the optic chiasm. METHODS. Adult G alpha i3 (-/-) and Oa1 (-/-) mice were compared with their respective control mice ( 129Sv and B6/ NCrl) to study the effects of the loss of G alpha i3 or Oa1 function. Light and electron microscopy were used to analyze the morphology of the retina and the size and density of RPE melanosomes, electroretinograms to study retinal function, and retrograde labeling to investigate the size of the uncrossed optic pathway. RESULTS. Although G alpha i3 (-/-) and Oa1 (-/-) photoreceptors were comparable to those of the corresponding control retinas, the density of their RPE melanosomes was significantly lower than in control RPEs. In addition, the RPE cells of G alpha i3 (-/-) and Oa1 -/- mice showed abnormal melanosomes that were far larger than the largest 129Sv and B6/ NCrl melanosomes, respectively. Although G alpha i3 (-/-) and Oa1 (-/-) mice had normal results on electroretinography, retrograde labeling showed a significant reduction from control in the size of their ipsilateral retinofugal projections. CONCLUSIONS. These results indicate that G alpha i3, like Oa1, plays an important role in melanosome biogenesis. Furthermore, they suggest a common Oa1-G alpha i3 signaling pathway that ultimately affects axonal growth through the optic chiasm. C1 [Young, Alejandra; Nusinowitz, Steven; Farber, Debora B.] Univ Calif Los Angeles, Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. [Jiang, Meisheng] Univ Calif Los Angeles, Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [Young, Alejandra; Farber, Debora B.] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90024 USA. [Powelson, Elisabeth B.; Whitney, Irene E.; Raven, Mary A.; Reese, Benjamin E.] Univ Calif Santa Barbara, Neurosci Res Inst, Santa Barbara, CA 93106 USA. [Powelson, Elisabeth B.; Whitney, Irene E.; Raven, Mary A.; Reese, Benjamin E.] Univ Calif Santa Barbara, Dept Psychol, Santa Barbara, CA 93106 USA. [Birnbaumer, Lutz] NIEHS, Transmembrane Signaling Grp, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. RP Farber, DB (reprint author), Univ Calif Los Angeles, Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. EM farber@jsei.ucla.edu FU Intramural NIH HHS; NEI NIH HHS [R01 EY015141, R01 EY015141-04, EY015141] NR 31 TC 16 Z9 16 U1 0 U2 1 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 JUL PY 2008 VL 49 IS 7 BP 3245 EP 3252 DI 10.1167/iovs.08-1806 PG 8 WC Ophthalmology SC Ophthalmology GA 318WR UT WOS:000257124000061 PM 18378571 ER PT J AU Mofenson, LM AF Mofenson, Lynne M. TI Antiretroviral prophylaxis to reduce breast milk transmission of HIV type 1: New data but still questions SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Editorial Material ID TO-CHILD TRANSMISSION; INFANT; PREVENTION; INFECTION; BOTSWANA; WOMEN C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH, Rockville, MD 20852 USA. RP Mofenson, LM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH, 6100 Executive Blvd,Room 4B11, Rockville, MD 20852 USA. EM LM65D@nih.gov OI Mofenson, Lynne/0000-0002-2818-9808 NR 36 TC 16 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JUL 1 PY 2008 VL 48 IS 3 BP 237 EP 240 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 319MT UT WOS:000257168500001 PM 18545160 ER PT J AU Hendrickson, SL Jacobson, LP Nelson, GW Phair, JP Lautenberger, J Johnson, RC Kingsley, L Margolick, JB Detels, R Goedert, JJ O'Brien, SJ AF Hendrickson, Sher L. Jacobson, Lisa P. Nelson, George W. Phair, John P. Lautenberger, James Johnson, Randall C. Kingsley, Lawrence Margolick, Joseph B. Detels, Roger Goedert, James J. O'Brien, Stephen J. TI Host genetic influences on highly active antiretroviral therapy efficacy and AIDS-free survival SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE AIDS; AIDS restriction gene; highly active antiretroviral therapy; single-nucleotide polymorphism ID IMMUNODEFICIENCY-VIRUS TYPE-1; HIV-1 DISEASE PROGRESSION; CCR5 DELTA-32 DELETION; HIV-1-INFECTED PATIENTS; VIROLOGICAL RESPONSE; CCR5-DELTA-32 MUTATION; PROMOTER POLYMORPHISM; COMBINATION THERAPY; TREATMENT FAILURE; T-CELLS AB We studied the influence of AIDS restriction genes (ARGs) CCR5-Delta 32, CCR2-64I, SDF1-5'A, IL10-5'A, CX3CRI-V249I, CX3CRI-T280M, and MDR1-C3435T and haplotypes of the CCR5 P1 promoter and RANTES variants -403A, In1.1C, 3'222C, and -28G among HIV-1 infected patients on highly active antiretroviral therapy (HAART) in the Multicenter AIDS Cohort Study (MACS) and the Multicenter Hemophilia Cohort Study (MHCS). Our results indicate that several ARGs also influence therapy efficacy (ie, the success in viral suppression) and subsequent progression to AIDS while on HAART. CCR5-Delta 32 decreased time to viral suppression (<200 HIV RNA copies/mL, relative hazard [RH] = 1.40; P = 0.008) and was protective against AIDS (RH = 0.11; P = <0.0001), whereas the CCR5 PI haplotype was associated with delayed viral suppression (RNA <50 copies/mL, odds ratio [OR] = 0.65; P = 0.03) and accelerated time to AIDS (RH 2.68; P = 0.02). SDF1-3'A reduced viral suppression (OR = 0.61; P = 0.02) and accelerated AIDS (RH = 3.18; P = 0.009). Accelerated AIDS progression was also observed with the RANTES haplotype carrying RANTES-IN1.1C and RANTES-3'222C (P = 0.005 to 0.007). In contrast, the RANTES haplotype HI, which lacks suspected deleterious single-nucleotide polymorphisms, was protective against AIDS. CX(3)CR1-V249I seemed to accelerate viral suppression (RNA <50 copies/mL, OR 1.27; P = 0.01). ARG influence after HAART suggests residual HIV-1 replication, and spread continues even in patients successfully suppressing detectable viral RNA. C1 [Hendrickson, Sher L.; Lautenberger, James; O'Brien, Stephen J.] NCI, Lab Genom Divers, Frederick, MD 21702 USA. [Jacobson, Lisa P.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Nelson, George W.; Johnson, Randall C.] Sci Applicat Int Corp Frederick Inc, Natl Canc Inst Frederick, Lab Genom Divers, Frederick, MD USA. [Phair, John P.] Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60611 USA. [Kingsley, Lawrence] Univ Pittsburgh, Dept Infect Dis & Microbiol, Pittsburgh, PA USA. [Margolick, Joseph B.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA. [Detels, Roger] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Detels, Roger] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Goedert, James J.] NCI, Viral Epidemiol Branch, Rockville, MD USA. RP Hendrickson, SL (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA. EM hendricksons@mail.nih.gov; obrien@ncifcrf.gov RI Johnson, Randall/B-1517-2014 OI Johnson, Randall/0000-0001-7754-0847 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400]; NCRR NIH HHS [5-M01-RR-00722, M01 RR000722]; NIAID NIH HHS [U01 AI037613, U01 AI035043, U01 AI037984, U01-AI-35039, U01-AI-35040, U01-AI-35041, U01-AI-35042, U01-AI-35043, U01-AI-37613, U01-AI-37984] NR 59 TC 31 Z9 33 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JUL 1 PY 2008 VL 48 IS 3 BP 263 EP 271 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 319MT UT WOS:000257168500005 PM 18391751 ER PT J AU Lutwama, F Serwadda, R Mayanja-Kizza, H Shihab, HM Ronald, A Kamya, MR Thomas, D Johnson, E Quinn, TC Moore, RD Spacek, LA AF Lutwama, Fred Serwadda, Ronnie Mayanja-Kizza, Harriet Shihab, Hasan M. Ronald, Allan Kamya, Moses R. Thomas, David Johnson, Elizabeth Quinn, Thomas C. Moore, Richard D. Spacek, Lisa A. TI Evaluation of dynabeads and cytospheres compared with flow cytometry to enumerate CD4+ T cells in HIV-infected Ugandans on antiretroviral therapy SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE CD4 lymphocyte counts; HIV-1 viral load; monitoring and evaluation; antiretroviral therapy; resource-limited setting; Uganda ID RESOURCE-LIMITED SETTINGS; DEVELOPING-COUNTRIES; ALTERNATIVE METHODS; LYMPHOCYTE COUNTS; ABSOLUTE CD4(+); MANUAL METHOD; IMPLEMENTATION; QUANTITATION; INDIVIDUALS; MARKERS AB Background: Laboratory-based monitoring of antiretroviral therapy is essential but adds a significant cost to HIV care. The World Health Organization 2006 guidelines support the use of CD4 lymphocyte count (CD4) to define treatment failure in resource-limited settings. Methods: We compared CD4 obtained on replicate samples from 497 HIV-positive Ugandans (before and during ART) followed for 18 months by 2 manual bead-based assays, Dynabeads (Dynal Biotech), and Cytospheres (Beckman Coulter) with those generated by flow cytometry at the Infectious Diseases Institute in Kampala, Uganda. Results: We tested 1671 samples (123 before ART) with Dynabeads and 1444 samples (91 before ART) with Cytospheres. Mean CD4 was 231 cells/mm(3) (SD, 139) and 239 celIS/MM3 (SD, 140) by Dynabeads and flow cytometry, respectively. Mean CD4 was 186 cells/mm(3) (SD, 10 1) and 242 cells/mm(3) (SD, 13 6) by Cytospheres and flow cytometry, respectively. The mean difference in CD4 count by flow cytometry versus Dynabeads were 8.8 cells/mm(3) (SD, 76.0) and versus Cytospheres were 56.8 cells/mm(3) (SD, 85.8). The limits of agreement were -140.9 to 158.4 cells/mm(3) for Dynabeads and -112.2 to 225.8 cells/mm(3) for Cytospheres. Linear regression analysis showed higher correlation between flow cytometry and Dynabeads (r = 0.85, r(2) = 0.73, slope = 0.85, intercept = 28) compared with the correlation between flow cytometry and Cytospheres (r = 0.78, r(2) = 0.60, slope = 0.58, intercept = 45). Area under the receiver operating characteristics curve to predict CD4 <200 cells/mm(3) was 0.928 for Dynabeads and 0.886 for Cylospheres. Conclusion: Although Dynabeads and Cytospheres both underestimated CD4 lymphocyte count compared with flow cytometry, in resource-limited settings with low daily throughput, manual bead-based assays may provide a less expensive alternative to flow cytometry. C1 [Shihab, Hasan M.; Thomas, David; Johnson, Elizabeth; Quinn, Thomas C.; Moore, Richard D.; Spacek, Lisa A.] Johns Hopkins Med Inst, Div Infect Dis, Baltimore, MD 21287 USA. [Lutwama, Fred; Serwadda, Ronnie; Ronald, Allan; Kamya, Moses R.] Acad Alliance AIDS Care & Prevent & Infect Dis In, Kampala, Uganda. [Ronald, Allan] Univ Manitoba, Winnipeg, MB, Canada. [Quinn, Thomas C.] NIAID, NIH, Bethesda, MD 20892 USA. [Mayanja-Kizza, Harriet; Kamya, Moses R.] Makerere Univ, Kampala, Uganda. RP Spacek, LA (reprint author), Johns Hopkins Med Inst, Div Infect Dis, 1830 E Monument St,Room 421, Baltimore, MD 21287 USA. EM lspacek@jhmi.edu OI Ronald, Allan/0000-0002-5746-3490 FU Intramural NIH HHS [Z01 AI000361-25]; NIAID NIH HHS [K-23 AI060384, K23 AI060384] NR 28 TC 9 Z9 10 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JUL 1 PY 2008 VL 48 IS 3 BP 297 EP 303 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 319MT UT WOS:000257168500009 PM 18545154 ER PT J AU Layman, AB Engels, EA AF Layman, Annah B. Engels, Eric A. TI Kidney and bladder cancers among people with AIDS in the United States SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Letter C1 [Layman, Annah B.; Engels, Eric A.] NCI, Infect & Immunoepiderniol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Layman, Annah B.] Brigham Young Univ, Dept Hlth Sci, Provo, UT 84602 USA. RP Layman, AB (reprint author), NCI, Infect & Immunoepiderniol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. FU Intramural NIH HHS NR 5 TC 8 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JUL 1 PY 2008 VL 48 IS 3 BP 365 EP 367 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 319MT UT WOS:000257168500023 PM 18580342 ER PT J AU Rowland, AS Skipper, B Rabiner, DL Umbach, DM Stallone, L Campbell, RA Hough, RL Naftel, AJ Sandler, DP AF Rowland, Andrew S. Skipper, Betty Rabiner, David L. Umbach, David M. Stallone, Lil Campbell, Richard A. Hough, Richard L. Naftel, A. J. Sandler, Dale P. TI The shifting subtypes of ADHD: Classification depends on how symptom reports are combined SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article DE attention-deficit hyperactivity disorder; ADHD; classification; subtypes; epidemiology ID ATTENTION-DEFICIT/HYPERACTIVITY-DISORDER; DEFICIT HYPERACTIVITY DISORDER; DSM-IV ADHD; CHILDHOOD PSYCHIATRIC-DISORDER; PREDOMINANTLY INATTENTIVE TYPE; TEACHER REPORTS; PREADOLESCENT GIRLS; GENDER-DIFFERENCES; BEHAVIOR PROBLEMS; REFERRED SAMPLE AB Research on the correlates of ADHD subtypes has yielded inconsistent findings, perhaps because the procedures used to define subtypes vary across studies. We examined this possibility by investigating whether the ADHD subtype distribution in a community sample was sensitive to different methods for combining informant data. We conducted a study to screen all children in grades 1-5 (N = 7847) in a North Carolina County for ADHD. Teachers completed a DSM-IV behavior rating scale and parents completed a structured telephone interview. We found substantial differences in the distribution of ADHD subtypes depending on whether one or both sources were used to define the subtypes. When parent and teacher data were combined, the procedures used substantially influenced subtype distribution. We conclude the ADHD subtype distribution is sensitive to how symptom information is combined and that standardization of the subtyping process is required to advance our understanding of the correlates of different ADHD subtypes. C1 [Rowland, Andrew S.] Univ New Mexico, Hlth Sci Ctr, MPH Program, Dept Family & Community Med, Albuquerque, NM 87131 USA. [Rabiner, David L.] Duke Univ, Ctr Child & Family Policy, Durham, NC 27707 USA. [Umbach, David M.] NIEHS, Biostat Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Stallone, Lil] CODA Inc, SES Div, Social & Sci Syst, Durham, NC 27703 USA. [Campbell, Richard A.; Hough, Richard L.] Univ New Mexico, Hlth Sci Ctr, Dept Psychiat, Albuquerque, NM 87131 USA. [Naftel, A. J.] Univ N Carolina, Sch Med, Dept Psychiat, Div Child & Adolescent Psychiat, Chapel Hill, NC 27514 USA. [Sandler, Dale P.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Rowland, AS (reprint author), Univ New Mexico, Hlth Sci Ctr, MPH Program, Dept Family & Community Med, Mailstop 09 5060,1 Univ New Mexico, Albuquerque, NM 87131 USA. EM arowland@salud.unm.edu OI Sandler, Dale/0000-0002-6776-0018 FU Intramural NIH HHS [Z01 ES049034-11]; NIEHS NIH HHS [P30 ES-012072, P30 ES012072]; NIMH NIH HHS [R01 MH071563, 5 R01 MH071563-01] NR 60 TC 20 Z9 22 U1 2 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0091-0627 J9 J ABNORM CHILD PSYCH JI J. Abnorm. Child Psychol. PD JUL PY 2008 VL 36 IS 5 BP 731 EP 743 DI 10.1007/s10802-007-9203-7 PG 13 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA 307LV UT WOS:000256321300009 PM 18347973 ER PT J AU Carney, RM Freedland, KE Steinmeyer, B Blumenthal, JA Berkman, LF Watkins, LL Czajkowski, SM Burg, MM Jaffe, AS AF Carney, Robert M. Freedland, Kenneth E. Steinmeyer, Brian Blumenthal, James A. Berkman, Lisa F. Watkins, Lana L. Czajkowski, Susan M. Burg, Matthew M. Jaffe, Allan S. TI Depression and five year survival following acute myocardial infarction: A prospective study SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE depressive disorder; acute myocardial infarction; mortality ID CORONARY-HEART-DISEASE; RISK-FACTOR; TREATING DEPRESSION; ENHANCING RECOVERY; MEDICAL MORBIDITY; PATIENTS ENRICHD; MORTALITY; SYMPTOMS; EVENTS; METAANALYSIS AB Depression has been shown to be a risk factor for mortality during the 12 months following an acute myocardial infarction (MI), but few studies have examined whether it is associated with increased risk over longer periods. Most of the existing studies utilized depression questionnaires rather than diagnostic interviews, the gold standard for clinical depression diagnosis. The purpose of this study was to determine whether interview-diagnosed clinical depression affects survival for at least 5 years after an acute MI. Vital status was determined for 163 patients with major depression, 195 with minor depression or dysthymia, and 408 nondepressed patients, during a median follow-up period of 60 months after an acute MI. Survival analysis was used to model time from the index NIT to death. There were 106 deaths during the follow-up. After adjusting for other risk factors for mortality, patients with either major or minor depression (HR = 1.76; 95% CI: 1.19 to 2.60), major depression alone (HR = 1.87; 95% CI: 1.17 to 2.98), or minor depression alone (HR= 1.67; 95% CI: 1.06 to 2.64) were at higher risk for all-cause mortality compared to the nondepressed patients. Depression is an independent risk factor for death 5 years after an acute MI. Even minor depression is associated with an increased risk. Although it is not known whether treating depression can improve survival, patients with depression should be recognized as being at increased risk long after their acute MI. (C) 2007 Elsevier B.V. All rights reserved. C1 [Carney, Robert M.; Freedland, Kenneth E.; Steinmeyer, Brian; Blumenthal, James A.; Watkins, Lana L.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Burg, Matthew M.; Jaffe, Allan S.] Dept Med, St Louis, MO USA. [Berkman, Lisa F.] Dept Epidemiol, St Louis, MO USA. [Blumenthal, James A.; Watkins, Lana L.] Duke Univ, Med Ctr, Durham, NC USA. [Berkman, Lisa F.] Harvard Univ, Boston, MA 02115 USA. [Czajkowski, Susan M.] NHLBI, Bethesda, MD 20892 USA. [Burg, Matthew M.] Yale Univ, Sch Med, New Haven, CT USA. [Jaffe, Allan S.] Mayo Clin, Rochester, MN USA. RP Carney, RM (reprint author), Behav Med Ctr, 4625 Lindell Blvd Suite 420, St Louis, MO 63108 USA. EM carneyr@bmc.wustl.edu FU NHLBI NIH HHS [2 R0-1HL58946, R01 HL058946-07, R01 HL058946] NR 27 TC 50 Z9 52 U1 1 U2 3 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 JUL PY 2008 VL 109 IS 1-2 BP 133 EP 138 DI 10.1016/j.jad.2007.12.005 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 316YY UT WOS:000256987300014 PM 18191208 ER PT J AU Laskibar, I Ortega-Alonso, A Pajala, S Urdaneta, E Yanguas, J Kaprio, J Rantanen, T AF Laskibar, Iker Ortega-Alonso, Alfredo Pajala, Satu Urdaneta, Elena Yanguas, Javier Kaprio, Jaalcko Rantanen, Taina TI Effect of consistent physical activity since midlife and educational history on dual task performance in older women SO JOURNAL OF AGING AND PHYSICAL ACTIVITY LA English DT Meeting Abstract C1 [Pajala, Satu] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Ortega-Alonso, Alfredo] Univ Helsinki, Dept Publ Hlth, FIN-00014 Helsinki, Finland. [Ortega-Alonso, Alfredo; Rantanen, Taina] Univ Jyvaskyla, Dept Hlth Sci, SF-40351 Jyvaskyla, Finland. RI Kaprio, Jaakko/A-1820-2008 NR 0 TC 0 Z9 0 U1 0 U2 1 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1063-8652 J9 J AGING PHYS ACTIV JI J. Aging Phys. Act. PD JUL PY 2008 VL 16 SU S BP S199 EP S200 PG 2 WC Geriatrics & Gerontology; Gerontology; Sport Sciences SC Geriatrics & Gerontology; Sport Sciences GA 333EL UT WOS:000258135400262 ER PT J AU Moir, S Fauci, AS AF Moir, Susan Fauci, Anthony S. TI Pathogenic mechanisms of B-lymphocyte dysfunction in HIV disease SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE HIV; B cells; immunopathogenesis; immune activation; lymphopenia; apoptosis ID ACTIVE ANTIRETROVIRAL THERAPY; T-CELL HOMEOSTASIS; IMMUNODEFICIENCY-VIRUS-INFECTION; NEUTRALIZING ANTIBODIES; HIV-1-INFECTED CHILDREN; PNEUMOCOCCAL DISEASE; RHESUS MACAQUES; NK CELLS; MEMORY; CD4(+) AB HIV disease is associated with abnormalities in all major lymphocyte populations, including B cells. Aberrancies in the B-cell compartment can be divided into 3 broad categories: changes that arise as a result of HIV-induced immune activation, changes that arise as a result of HIV-induced lymphopenia, and changes that arise independently of these 2 parameters. We review recent developments in all 3 categories of abnormalities and highlight how observations made in the early years of the HIV epidemic are better understood today in large part because of the advent of effective antiretroviral therapy. Insight into the mechanisms of B-cell dysfunction in HIV disease has also been achieved as a result of increased knowledge of the B-cell subpopulations as they exist in healthy individuals, compared with their abnormalities in HIV-infected individuals. A better understanding of the pathogenic mechanisms of B-cell abnormalities in HIV disease can potentially lead to new strategies for improving antibody responses against opportunistic pathogens that afflict HIV-infected individuals and against HIV itself, in the context of both HIV infection and an antibody-based HIV vaccine. C1 [Moir, Susan; Fauci, Anthony S.] Natl Inst Allergy & Infect Dis, Immunoregulat Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Moir, S (reprint author), Natl Inst Allergy & Infect Dis, Immunoregulat Lab, Natl Inst Hlth, 9000 Rockville Pike,Bldg 10,Room 6A02, Bethesda, MD 20892 USA. EM smoir@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000825-10] NR 80 TC 87 Z9 90 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 JUL PY 2008 VL 122 IS 1 BP 12 EP 19 DI 10.1016/j.jaci.2008.04.034 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 325RD UT WOS:000257605100002 PM 18547629 ER PT J AU Elliott, L Henderson, J Northstone, K Chiu, GY Dunson, D London, SJ AF Elliott, Leslie Henderson, John Northstone, Kate Chiu, Grace Y. Dunson, David London, Stephanie J. TI Prospective study of breast-feeding in relation to wheeze, atopy, and bronchial hyperresponsiveness in the Avon Longitudinal Study of Parents and Children (ALSPAC) SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE asthma; atopy; breast-feeding; bronchial hyperresponsiveness; allergy ID BIRTH COHORT; RISK-FACTORS; EARLY-CHILDHOOD; ASTHMA; DERMATITIS; DISEASE; LIFE; EPIDEMIOLOGY; METHODOLOGY; HISTORY AB Background: Breast-feeding clearly protects against early wheezing, but recent data suggest that it might increase later risk of atopic disease and asthma. Objective: We sought to examine the relationship between breast-feeding and later asthma and allergy outcomes by using data from the Avon Longitudinal Study of Parents and Children, a large birth cohort in the United Kingdom. Methods: We used adjusted logistic regression models to evaluate the association between breast-feeding and atopy at age 7 years, bronchial responsiveness to methacholine at age 8 years, and wheeze at ages 3 and 7 1/2 years. Bayesian methods were used to assess the possibility of bias caused by an influence of early wheezing: on the duration of breast-feeding, as well as selection bias. Results: Breast-feeding was protective for wheeze in the first 3 years of life (odds ratio [OR] of 0.80 [95% CI, 0.70-0.90] for >= 6 months relative to never) but not wheeze (OR, 0.98; 95% CI, 0.79-1.22), atopy (OR, 1.12; 95% Cl, 0.92-1.35), or bronchial hyperresponsiveness (OR, 1.07; 95% CI, 0.82-1.40) at ages 7 to 8 years. Bayesian models adjusting for the longer duration of breast-feeding among children with wheezing in early infancy produced virtually identical results. Conclusions: We did not find consistent evidence for either a deleterious effect or a protective effect of breast-feeding on later risk of allergic disease in a large prospective birth cohort of children with objective outcome measures and extensive data on potential confounders and effect modifiers. Neither reverse causation nor loss to follow-up appears to have materially biased our results. C1 [Elliott, Leslie; London, Stephanie J.] NIEHS, Epidemiol Branch, Div Intramural Res, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Dunson, David] NIEHS, Biostat Branch, Div Intramural Res, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Henderson, John; Northstone, Kate] Univ Bristol, Dept Social Med, Bristol BS8 1TH, Avon, England. [Henderson, John] Bristol Royal Hosp Children, Dept Resp Med, Bristol, Avon, England. [Chiu, Grace Y.] Westat Corp, Res Triangle Pk, NC USA. RP London, SJ (reprint author), NIEHS, Epidemiol Branch, Div Intramural Res, NIH,Dept Hlth & Human Serv, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. EM london2@niehs.nih.gov RI Northstone, Kate/A-8165-2011; OI Northstone, Kate/0000-0002-0602-1983; London, Stephanie/0000-0003-4911-5290 FU Intramural NIH HHS [Z99 ES999999, Z01 ES049019-12]; Medical Research Council [, G0401540, G9815508]; Wellcome Trust NR 33 TC 51 Z9 58 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 JUL PY 2008 VL 122 IS 1 BP 49 EP 54 DI 10.1016/j.jaci.2008.04.001 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 325RD UT WOS:000257605100008 PM 18468669 ER PT J AU Foster, SB McIntosh, K Thompson, B Lu, M Yin, W Rich, KC Mendez, H Serchuck, LK Diaz, C Paul, ME Shearer, WT AF Foster, Samuel B. McIntosh, Kenneth Thompson, Bruce Lu, Ming Yin, Wanrong Rich, Kenneth C. Mendez, Hermann Serchuck, Leslie K. Diaz, Clemente Paul, Mary E. Shearer, William T. TI Increased incidence of asthma in HIV-infected children treated with highly active antiretroviral therapy in the National Institutes of Health Women and Infants Transmission Study SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE pediatric HIV infection; CD4(+) T cell-mediated induction of asthma; highly active antiretroviral therapy--produced immunoreconstitution ID AIRWAY INFLAMMATION; VIRAL-INFECTIONS; HYPERRESPONSIVENESS; HYPERREACTIVITY; INDIVIDUALS; PREVALENCE; PATHOLOGY; DISEASES; MODELS; AIDS AB Background: Immunoreconstitution of HIV+ patients after treatment with highly active antiretroviral therapy (HAART) appears to provoke inflammatory diseases. Objective: We sought to determine whether HIV+ children receiving HAART(HIV+ HAART(+)) have a higher incidence of asthma than HIV+ children not receiving HAART (HIV+ HAART(-)). Methods: Two thousand six hundred sixty-four children (193 HIV+ and 2471 HIV- children) born to HIV+ women were evaluated for the incidence and prevalence of asthma (ie, asthma medication use) and change of CD4(+) T-cell percentage with time. Results: The HIV+ HAART(+) children had higher CD4(+) T-cell percentages, lower CD8(+) T-cell percentages, and lower viral burdens than the HIV+ HAART(-) children (P <= .05 to P <= .01). The cumulative incidence of asthma medication use in HIV+ HAART(+) children at 13.5 years increased to 33.5% versus 11.5% in HIV+ HAART(-) children (hazard ratio, 3.34; P = .01) and was equal to that in the HIV- children. In children born before the HAART era, the prevalence of asthma medication use for HIV+ HAART(+) children at 11 years of age was 10.4% versus 3.8% for HIV+ HAART(-) children (odds ratio, 3.38; P = .02) and was equal to that of the HIV- children. The rate of change of CD4(+) IF cells around the time of first asthma medication for HIV+ HAART(+) versus HIV+ HAART(--) children was 0.81 %/y versus -1.43 %/y (P = .01). Conclusion: The increased incidence of asthma in HIV+ HAART(+) children might be driven by immunoreconstitution of CD4(+) T cells. C1 [Foster, Samuel B.; Paul, Mary E.; Shearer, William T.] Texas Childrens Hosp, Houston, TX 77030 USA. [Foster, Samuel B.; Paul, Mary E.; Shearer, William T.] Baylor Coll Med, Dept Pediat, Allergy & Immunol Sect, Houston, TX 77030 USA. [McIntosh, Kenneth] Harvard Univ, Childrens Hosp, Sch Med, Div Infect Dis, Boston, MA 02115 USA. [Thompson, Bruce; Lu, Ming; Yin, Wanrong] Clin Trials & Surveys Corp, Baltimore, MD USA. [Rich, Kenneth C.] Univ Illinois, Dept Pediat, Chicago, IL USA. [Mendez, Hermann] SUNY, Dept Pediat, Brooklyn, NY USA. [Serchuck, Leslie K.] NICHHD, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD 20892 USA. [Diaz, Clemente] Puerto Rico Sch Med, Dept Pediat, San Juan, PR USA. RP Shearer, WT (reprint author), Texas Childrens Hosp, 6621 Fannin St MC FC330-01, Houston, TX 77030 USA. EM wtsheare@TexasChildrensHospital.org FU NCRR NIH HHS [RR0188, K01 RR000188, M01 RR000188]; NHLBI NIH HHS [HL079533, HL72705, HL96040, R01 HL072705, R01 HL079533]; NIAID NIH HHS [AI36211, U01 AI034840, P30 AI036211, AI27551, U01 AI027551, U01 AI034840-08, U01 AI041089, AI41089]; NICHD NIH HHS [HD41983, U01 HD041983] NR 39 TC 26 Z9 28 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUL PY 2008 VL 122 IS 1 BP 159 EP 165 DI 10.1016/j.jaci.2008.04.043 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 325RD UT WOS:000257605100026 PM 18547627 ER PT J AU Sannes, TS Mansky, PJ Chesney, MA AF Sannes, Timothy S. Mansky, Patrick J. Chesney, Margaret A. TI The need for attention to dose in mind-body interventions: Lessons from T'ai chi clinical trials SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; VARICELLA-ZOSTER-VIRUS; QUALITY-OF-LIFE; OLDER-ADULTS; CANCER SURVIVORS; REDUCING FRAILTY; AEROBIC EXERCISE; BALANCE; CHUAN; HEALTH AB Objective: The rise in popularity of complementary and alternative medicine (CAM) in the United States has stimulated increasing interest in researching CAM. One challenge to this research is determining the optimal dose of a CAM intervention. T'ai Chi Chuan (TCC) has received considerable attention as a mind-body practice; however, it remains unclear exactly how much TCC practice is necessary to elicit a discernable effect. Design: In this review, we selected 19 studies and examined the variation in the number and length of training sessions. Secondary and tertiary aims include examining attendance rates for each intervention and the instructions given to participants regarding home-based practice. The degree to which investigators monitored participants' home-based practice was also examined. Results: In the intent-to-treat analyses, the median time of TCC practice was 2877 minutes intended for participants across the selected interventions. Fourteen (14) of the publications provided information about participant attendance in the original publication, 2 provided additional information through further author inquiry, and 3 commented on TCC practice outside of the structured class environment through author inquiry. Conclusions: The data reported are inconsistent in reported attendance and home-based practice rates, making it difficult to speculate on the relationship between the amount of TCC and intervention effects. Further research could contribute to this area by determining the optimal dose of TCC instruction. C1 [Sannes, Timothy S.] Univ Florida, Dept Clin & Hlth Psychol, Gainesville, FL 32611 USA. [Sannes, Timothy S.; Mansky, Patrick J.] NCCAM, Bethesda, MD USA. [Chesney, Margaret A.] Univ Maryland, Baltimore, MD 21201 USA. RP Sannes, TS (reprint author), Univ Florida, Dept Clin & Hlth Psychol, 101 S Newell Dr, Gainesville, FL 32611 USA. EM tsannes@phhp.ufl.edu NR 33 TC 7 Z9 7 U1 3 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD JUL PY 2008 VL 14 IS 6 BP 645 EP 653 DI 10.1089/acm.2007.0680 PG 9 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 344WG UT WOS:000258957400009 PM 18684072 ER PT J AU Onufrieva, KS Brewster, CC Thorpe, KW Sharov, AA Leonard, DS Reardon, RC Mastro, VC Sellers, P Roberts, EA AF Onufrieva(Tcheslavskaia), K. S. Brewster, C. C. Thorpe, K. W. Sharov, A. A. Leonard, D. S. Reardon, R. C. Mastro, V. C. Sellers, P. Roberts, E. A. TI Effects of the 3M (TM) MEC Sprayable Pheromone (R) formulation on gypsy moth mating success SO JOURNAL OF APPLIED ENTOMOLOGY LA English DT Article ID SEX ATTRACTANT; PHEROMONE; LYMANTRIIDAE; LEPIDOPTERA; DISRUPTION; DISPARLURE AB The study was conducted during 2000, 2001, 2003 and 2004 in forested areas in Virginia, USA to evaluate the 3M (TM) MEC-GM Sprayable Pheromone (R) formulation of the gypsy moth sex pheromone, disparlure, for its ability to disrupt mating in gypsy moth, Lymantria dispar (Lep.: Lymantriidae). Both mating success of gypsy moth females and male moth catches in pheromone-baited traps were significantly reduced in plots treated with the 3M (TM) MEC-GM formulation at dosages ranging from 15 to 75 g of active ingredient/ha. However, the 3M (TM) MEC-GM formulation reduced trap catch to a lesser extent than did the currently registered Hercon Disrupt (R) II plastic flakes used as a positive control and applied at similar or lower dosages. Furthermore, the effectiveness of the 3M (TM) sprayable formulation declined through time, so that by the end of the male flight season, male moth catches in traps were significantly higher than in plots treated with Hercon plastic flakes. Based on the reported results, 3M (TM) MEC-GM Sprayable Pheromone (R) formulation was never integrated into the operational treatment projects of USDA Forest Service Cooperative Slow-the-Spread of the Gypsy Moth management programme. C1 [Onufrieva(Tcheslavskaia), K. S.; Brewster, C. C.; Roberts, E. A.] Virginia Tech, Dept Entomol, Blacksburg, VA 24061 USA. [Thorpe, K. W.] ARS, USDA, Beltsville, MD USA. [Sharov, A. A.] NIA, NIH, Pasadena, MD USA. [Leonard, D. S.] US Forest Serv, USDA, Asheville, NC USA. [Reardon, R. C.] US Forest Serv, USDA, Morgantown, WV USA. [Sellers, P.] US Forest Serv, USDA, Harrisonburg, VA USA. RP Onufrieva, KS (reprint author), Virginia Tech, Dept Entomol, 202 Price Hall, Blacksburg, VA 24061 USA. EM ktchesla@vt.edu RI Onufrieva, Ksenia/A-4609-2008 OI Onufrieva, Ksenia/0000-0002-8424-850X NR 25 TC 3 Z9 3 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0931-2048 J9 J APPL ENTOMOL JI J. Appl. Entomol. PD JUL PY 2008 VL 132 IS 6 BP 461 EP 468 DI 10.1111/j.1439-0418.2007.01262.x PG 8 WC Entomology SC Entomology GA 311RU UT WOS:000256618100005 ER PT J AU Swanson, J Arnold, LE Kraemer, H Hechtman, L Molina, B Hinshaw, S Vitiello, B Jensen, P Steinhoff, K Lerner, M Greenhill, L Abikoff, H Wells, K Epstein, J Elliott, G Newcorn, J Hoza, B Wigal, T AF Swanson, James Arnold, L. Eugene Kraemer, Helena Hechtman, Lily Molina, Brooke Hinshaw, Stephen Vitiello, Benedetto Jensen, Peter Steinhoff, Ken Lerner, Marc Greenhill, Laurence Abikoff, Howard Wells, Karen Epstein, Jeffery Elliott, Glen Newcorn, Jeffrey Hoza, Betsy Wigal, Timothy CA MTA Cooperative Grp TI Evidence, Interpretation, and Qualification From Multiple Reports of Long-Term Outcomes in the Multimodal Treatment Study of Children With ADHD (MTA) Part I: Executive Summary SO JOURNAL OF ATTENTION DISORDERS LA English DT Article DE attention deficit/hyperactivity disorder; multimodal treatment; randomized clinical trial; stimulant medication; behavior modification AB Objective: To review the primary and secondary findings from the Multimodal Treatment study of ADHD (MTA) published over the past decade as three sets of articles. Method: In a two-part article-Part I: Executive Summary (without distracting details) and Part II: Supporting Details (with additional background and detail required by the complexity of the MTA)-we address confusion and controversy about the findings. Results: We discuss the basic features of the gold standard used to produce scientific evidence, the randomized clinical trial, for which was used to contrast four treatment conditions: medication management alone (MedMgt), behavior therapy alone (Beh), the combination of these two (Comb), and a community comparison of treatment "as usual" (CC). For each of the three assessment points we review three areas that we believe are important for appreciation of the findings: definition of evidence from the MTA, interpretation of the serial presentations of findings at each assessment point with a different definition of long-term, and qualification of the interim conclusions about long-term effects of treatments for ADHD. Conclusion: We discuss the possible clinical relevance of the MTA and present some practical suggestions based on current knowledge and uncertainties facing families, clinicians, and investigators regarding the long-term use of stimulant medication and behavioral therapy in the treatment of children with ADHD. (J. of Att. Dis. 2008; 12(1) 4-14) C1 [Swanson, James] UCI Child Dev Ctr, Irvine, CA 92612 USA. [Swanson, James] Univ Calif Irvine, Irvine, CA USA. [Arnold, L. Eugene] Ohio State Univ, Nisonger Ctr, Columbus, OH 43210 USA. [Kraemer, Helena] Stanford Univ, Stanford, CA 94305 USA. [Hechtman, Lily] McGill Univ, Montreal, PQ H3A 2T5, Canada. [Molina, Brooke] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Hinshaw, Stephen] Univ Calif Berkeley, Berkeley, CA USA. [Vitiello, Benedetto] NIMH, Child & Adolescent Treatment & Prevent Intervent, Bethesda, MD USA. [Greenhill, Laurence] Columbia Univ, New York, NY USA. [Abikoff, Howard] NYU, New York, NY 10003 USA. [Wells, Karen] Duke Univ, Durham, NC 27706 USA. [Epstein, Jeffery] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Elliott, Glen] Stanford Sch Med, Stanford, CA USA. [Newcorn, Jeffrey] Mt Sinai Sch Med, New York, NY USA. [Hoza, Betsy] Univ Vermont, Burlington, VT 05405 USA. [Wigal, Timothy] Univ Calif Irvine, Irvine, CA USA. RP Swanson, J (reprint author), UCI Child Dev Ctr, 19722 MacArthur Blvd, Irvine, CA 92612 USA. EM jmswanso@uci.edu OI Jensen, Peter/0000-0003-2387-0650; Newcorn, Jeffrey /0000-0001-8993-9337 FU National Institute of Mental Health [U01 MH50461, N01MH12009, U01 MH50477, N01MH12012, U01 MH50440, N01MH 12011, U01 MH50467, N01 MH12007, U01 MH50453, N01MH 12004, N01 MH 12010, N01MH12008]; U.S. Department of Education; Office of Juvenile Justice and Delinquency Prevention of the Justice Department; National Institute on Drug Abuse FX The work reported was supported by cooperative agreement grants and contracts from the National Institute of Mental Health to the following: University of California, Berkeley: U01 MH50461 and N01MH12009; Duke University: U01 MH50477 and N01MH12012; University of California, Irvine: U01 MH50440 and N01MH 12011; Research Foundation for Mental Hygiene (New York State Psychiatric Institute/Columbia University): U01 MH50467and N01 MH12007; Long Island-Jewish Medical Center U01 MH50453; New York University: N01MH 12004; University of Pittsburgh: U01 MH50467 and N01 MH 12010; McGill University N01MH12008. The Office of Special Education Programs of the U.S. Department of Education, the Office of Juvenile Justice and Delinquency Prevention of the Justice Department, and the National Institute on Drug Abuse also participated in funding. NR 8 TC 48 Z9 48 U1 2 U2 17 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0547 J9 J ATTEN DISORD JI J. Atten. Disord. PD JUL PY 2008 VL 12 IS 1 BP 4 EP 14 DI 10.1177/1087054708319345 PG 11 WC Psychology, Developmental; Psychiatry SC Psychology; Psychiatry GA V11GS UT WOS:000207520700002 PM 18573923 ER PT J AU Swanson, J Arnold, LE Kraemer, H Hechtman, L Molina, B Hinshaw, S Vitiello, B Jensen, P Steinhoff, K Lerner, M Greenhill, L Abikoff, H Wells, K Epstein, J Elliott, G Newcorn, J Hoza, B Wigal, T AF Swanson, James Arnold, L. Eugene Kraemer, Helena Hechtman, Lily Molina, Brooke Hinshaw, Stephen Vitiello, Benedetto Jensen, Peter Steinhoff, Ken Lerner, Marc Greenhill, Laurence Abikoff, Howard Wells, Karen Epstein, Jeffery Elliott, Glen Newcorn, Jeffrey Hoza, Betsy Wigal, Timothy CA MTA Cooperative Grp TI Evidence, Interpretation, and Qualification From Multiple Reports of Long-Term Outcomes in the Multimodal Treatment Study of Children With ADHD (MTA) Part II: Supporting Details SO JOURNAL OF ATTENTION DISORDERS LA English DT Article DE attention-deficit/hyperactivity disorder; multimodal treatment; randomized clinical trial; stimulant medication; behavior modification AB Objective: To review and provide details about the primary and secondary findings from the Multimodal Treatment study of ADHD (MTA) published during the past decade as three sets of articles. Method: In the second of a two part article, we provide additional background and detail required by the complexity of the MTA to address confusion and controversy about the findings outlined in part I (the Executive Summary). Results: We present details about the gold standard used to produce scientific evidence, the randomized clinical trial (RCT), which we applied to evaluate the long-term effects of two well-established unimodal treatments, Medication Management (MedMGT) and behavior therapy (Beh), the multimodal combination (Comb), and treatment "as usual" in the community (CC). For each of the first three assessment points defined by RCT methods and included in intent-to-treat analyses, we discuss our definition of evidence from the MTA, interpretation of the serial presentations of findings at each assessment point with a different definition of long-term varying from weeks to years, and qualification of the interim conclusions about long-term effects of treatments for ADHD based on many exploratory analyses described in additional published articles. Conclusions: Using a question and answer format, we discuss the possible clinical relevance of the MTA and present some practical suggestions based on current knowledge and uncertainties facing families, clinicians, and investigators regarding the long-term use of stimulant medication and behavioral therapy in the treatment of children with ADHD. (J. of Att. Dis. 2008; 12(1) 15-43) C1 [Swanson, James] Univ Calif Irvine, Irvine, CA 92717 USA. [Arnold, L. Eugene] Ohio State Univ, Nisonger Ctr, Columbus, OH 43210 USA. [Kraemer, Helena] Stanford Univ, Stanford, CA 94305 USA. [Hechtman, Lily] McGill Univ, Montreal, PQ H3A 2T5, Canada. [Molina, Brooke] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Hinshaw, Stephen] Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA. [Vitiello, Benedetto] NIMH, Child & Adolescent Treatment & Prevent Intervent, Bethesda, MD USA. [Greenhill, Laurence] Columbia Univ, New York, NY 10027 USA. [Abikoff, Howard] NYU, New York, NY 10003 USA. [Wells, Karen] Duke Univ, Durham, NC 27706 USA. [Epstein, Jeffery] Cincinnati Childrens Hosp, Med Ctr, Div Behav Med & Clin Psychol, Cincinnati, OH USA. [Elliott, Glen] Stanford Sch Med, Stanford, CA USA. [Newcorn, Jeffrey] Mt Sinai Sch Med, New York, NY USA. [Hoza, Betsy] Univ Vermont, Burlington, VT 05405 USA. [Wigal, Timothy] Univ Calif Irvine, Irvine, CA USA. RP Swanson, J (reprint author), Univ Calif Irvine, Irvine, CA 92717 USA. OI Jensen, Peter/0000-0003-2387-0650; Newcorn, Jeffrey /0000-0001-8993-9337 FU National Institute of Mental Health [U01 MH50461, N01MH12009, U01 MH50477, N01MH12012, U01 MH50440, N01MH 12011, U01 MH50467, N01 MH12007, U01 MH50453, N01MH 12004, N01 MH 12010, N01MH12008]; U.S. Department of Education; Office of Juvenile Justice and Delinquency Prevention of the Justice Department; National Institute on Drug Abuse FX The work reported was supported by cooperative agreement grants and contracts from the National Institute of Mental Health to the following: University of California, Berkeley: U01 MH50461 and N01MH12009; Duke University: U01 MH50477 and N01MH12012; University of California, Irvine: U01 MH50440 and N01MH 12011; Research Foundation for Mental Hygiene (New York State Psychiatric Institute/Columbia University): U01 MH50467and N01 MH12007; Long Island-Jewish Medical Center U01 MH50453; New York University: N01MH 12004; University of Pittsburgh: U01 MH50467 and N01 MH 12010; McGill University N01MH12008. The Office of Special Education Programs of the U.S. Department of Education, the Office of Juvenile Justice and Delinquency Prevention of the Justice Department, and the National Institute on Drug Abuse also participated in funding. NR 63 TC 45 Z9 46 U1 3 U2 14 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0547 J9 J ATTEN DISORD JI J. Atten. Disord. PD JUL PY 2008 VL 12 IS 1 BP 15 EP 43 DI 10.1177/1087054708319525 PG 29 WC Psychology, Developmental; Psychiatry SC Psychology; Psychiatry GA V11GS UT WOS:000207520700003 PM 18573924 ER PT J AU Miech, R Azur, M Dusablon, T Jowers, K Goldstein, AB Stuart, EA Walrath, C Leaf, PJ AF Miech, Richard Azur, Melissa Dusablon, Tracy Jowers, Keri Goldstein, Amy B. Stuart, Elizabeth A. Walrath, Christine Leaf, Philip J. TI The potential to reduce mental health disparities through the Comprehensive Community Mental Health Services for Children and Their Families Program SO JOURNAL OF BEHAVIORAL HEALTH SERVICES & RESEARCH LA English DT Article ID PSYCHIATRIC-DISORDER; ADOLESCENTS; POVERTY; YOUTHS; RISK AB Few service systems are currently in place with the explicit purpose to reduce youth mental health disparities across socioeconomic status and race-ethnicity, despite substantial interest by the federal government and other institutions to redress health disparities. This study examines the potential for the Comprehensive Community Mental Health Services for Children and Their Families Program to address health disparities, even though this program was not explicitly designed for disparity reduction. Specifically, this study examines whether program sites disproportionately provide services within their catchment areas for youth who come from poor families, who are Black, and who are Hispanic. Data for this study come from 45 sites and 19,189 youth who were enrolled in program sites from 1997 to 2005. Meta-analysis was used to generate Forest plots and to obtain single, pooled estimates of risk ratios and their standard errors across all Children's Mental Health Initiative communities. The results indicate that in comparison to the targeted catchment area (a) the percentage poor youth in the programs was almost three times higher, (b) the percentage Black in the programs was about twice as high, and (c) the percentage Hispanic in the programs was about the same. These results indicate that the program successfully reaches disadvantaged youth and can bring substantial infrastructure to address youth mental health disparities. In fact, to the extent that the program successfully improves mental health among enrollees it may be serving as one of the largest initiatives to redress health disparities, although its role in disparity reduction is not widely recognized. C1 [Miech, Richard] Univ Colorado, Dept Hlth & Behav Sci, Denver, CO 80217 USA. [Azur, Melissa; Dusablon, Tracy; Jowers, Keri; Stuart, Elizabeth A.; Leaf, Philip J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD 21205 USA. [Goldstein, Amy B.] NIMH, Child & Adolescent Prevent Intervent Program, Bethesda, MD 20892 USA. [Stuart, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. [Walrath, Christine] Macro Int Inc, New York, NY 10038 USA. [Leaf, Philip J.] Johns Hopkins Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. RP Miech, R (reprint author), Univ Colorado, Dept Hlth & Behav Sci, Campus Box 188,POB 173364, Denver, CO 80217 USA. EM rmiech@gmail.com; mazur@jhsph.edu; trpatter@jhsph.edu; kjowers@jhsph.edu; goldsteinam@mail.nih.gov; estuart@jhsph.edu; cwalrath@macrointernational.com; pleaf@jhsph.edu RI Miech, Richard/B-3170-2016; OI Miech, Richard/0000-0002-2722-3277; Stuart, Elizabeth/0000-0002-9042-8611 FU NIMH NIH HHS [1R01MH075828, R01 MH075828, R01 MH075828-02] NR 23 TC 12 Z9 12 U1 8 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1094-3412 J9 J BEHAV HEALTH SER R JI J. Behav. Health Serv. Res. PD JUL PY 2008 VL 35 IS 3 BP 253 EP 264 DI 10.1007/s11414-008-9123-5 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 324CX UT WOS:000257496400003 PM 18543110 ER PT J AU Pastrana, DV Yun, CH McKee, ML FitzGerald, DJ AF Pastrana, Diana V. Yun, Cheol H. McKee, Marian L. FitzGerald, David J. TI Mammalian cell expression of an active site mutant of Pseudomonas exotoxin disrupts LRP1 maturation SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Article DE toxin; secretion; ERAD; receptor; LRP1 ID RECEPTOR-RELATED PROTEIN; RETROGRADE TRANSPORT; ENDOPLASMIC-RETICULUM; ALZHEIMERS-DISEASE; ESCHERICHIA-COLI; DIPHTHERIA-TOXIN; AERUGINOSA; FURIN; DELETION; TRANSLOCATION AB Low density lipoprotein receptor-related protein 1, (LRP1) is a large multifunctional receptor that binds more than 25 physiologic ligands. In addition, it functions as the surface receptor for several Rhinoviruses, HIV-tat and Pseudomonas exotoxin (PE). We report that the expression of PE within mammalian cells can serve as a probe of LRP1 maturation and functionality. To avoid cell killing, an enzymatically inactive form of the toxin (PE Delta 553) was expressed. A permanent cell line (termed CY301) was established whereby PE Delta 553 was expressed continually into the ER of CHO cells. CY301 cells were 100-fold resistant to exogenously added active PE but exhibited no cross-resistance to other toxins. Our studies indicate that PE Delta 553 bound to immature LRP1 in the ER, prevented its maturation to the cell surface and thereby produced a toxin resistant phenotype. By confocal microscopy, cell-associated PE Delta 553 was localized to the ER and co-localized with LRP1. Further characterization of CY301 cells indicated that RAP, the chaperone that aids in LRP1 folding, was released to the growth media. Thus the intracellular expression of PE Delta 553 appears to be a valuable probe of LRP1 maturation and trafficking. C1 [FitzGerald, David J.] LMB, Biotherapy Sect, Bethesda, MD 20892 USA. [Pastrana, Diana V.; Yun, Cheol H.; McKee, Marian L.; FitzGerald, David J.] NCI, Mol Biol Lab, CCR, US Dept HHS,NIH, Bethesda, MD USA. RP FitzGerald, DJ (reprint author), LMB, Biotherapy Sect, 37-5124,37 Convent Dr MSC 4264, Bethesda, MD 20892 USA. EM djpf@helix.nih.gov OI YUN, Cheol-Heui/0000-0002-0041-2887 NR 40 TC 4 Z9 4 U1 2 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PD JUL PY 2008 VL 15 IS 4 BP 427 EP 439 DI 10.1007/s11373-008-9245-z PG 13 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 309PE UT WOS:000256471900002 PM 18351442 ER PT J AU Rose, JJ Foley, JF Yi, L Herren, G Venkatesan, S AF Rose, Jeremy J. Foley, John F. Yi, Ling Herren, Gina Venkatesan, Sundararajan TI Cholesterol is obligatory for polarization and chemotaxis but not for endocytosis and associated signaling from chemoattractant receptors in human neutrophils SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Article DE neutrophils; chemotaxis; cholesterol; lipid rafts; chemoattractants; G-proteins; endocytosis; arrestin; degranulation; protein kinases; F-actin ID MET-LEU-PHE; LIPID RAFTS; CHEMOKINE RECEPTORS; BETA-ARRESTIN; LEADING-EDGE; ASYMMETRIC LOCALIZATION; LYMPHOCYTE CHEMOTAXIS; DOMAIN SEGREGATION; PEPTIDE RECEPTORS; ERK1/2 ACTIVATION AB Plasma membrane cholesterol is critical for neutrophil chemotaxis, although how cholesterol affects chemotactic signaling pathway has not been clearly delineated. Here we demonstrate that cholesterol was absolutely required for polarized redistribution of key chemotactic mediators in human neutrophils in response to all chemoattractants tested (fMet-Leu-Phe, and the chemokines CXCL1, CXCL8 and CXCL12). In particular, PI3K and phosphatidylinositol-3,4,5 triphosphate (PIP(3)) failed to accumulate at the front and phosphatase and tensin homolog (PTEN) at the back of chemoattractant-stimulated neutrophils after cholesterol depletion. Cholesterol depletion did not affect early chemoattractant signaling events such as G-protein activation, intracellular calcium flux or G-protein-independent endocytosis-linked signaling, including the activation of mitogen-activated protein kinase (MAPK), Hck and Fgr transduced by beta-arrestin. During cell polarization, F-actin assemblies redistributed the cholesterol-rich microdomains and cytoskeleton-anchored proteins, including CD16 and CD44 from the leading edge. These data suggest that spatial polarization of chemotactic mediators is orchestrated by protein:protein interactions that organize cholesterol-rich domains of the plasma membrane. C1 [Rose, Jeremy J.; Foley, John F.; Yi, Ling; Herren, Gina; Venkatesan, Sundararajan] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Venkatesan, S (reprint author), NIAID, Lab Mol Immunol, NIH, Bldg 10,Room 6A05, Bethesda, MD 20892 USA. EM aradhana@helix.nih.gov; sv1s@nih.gov FU Intramural NIH HHS NR 75 TC 7 Z9 7 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PD JUL PY 2008 VL 15 IS 4 BP 441 EP 461 DI 10.1007/s11373-008-9239-x PG 21 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 309PE UT WOS:000256471900003 PM 18311596 ER PT J AU Russo, AM Poole, JE Mark, DB Anderson, J Hellkamp, AS Lee, KL Johnson, GW Domanski, M Bardy, GH AF Russo, Andrea M. Poole, Jeanne E. Mark, Daniel B. Anderson, Jill Hellkamp, Anne S. Lee, Kerry L. Johnson, George W. Domanski, Michael Bardy, Gust H. CA SCD-HeFT Investigators TI Primary prevention with defibrillator therapy in women: Results from the Sudden Cardiac Death in Heart Failure Trial SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE arrhythmia; sudden death; tachycardia; gender; primary prevention ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS; SUSTAINED VENTRICULAR TACHYARRHYTHMIAS; CORONARY-ARTERY-DISEASE; GENDER-DIFFERENCES; SEX-DIFFERENCES; DE-POINTES; ARREST; SURVIVORS; RISK; PROARRHYTHMIA AB Introduction: The Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) demonstrated that implantable cardioverter defibrillator (ICD) therapy reduced overall mortality in patients with class II or III heart failure and left ventricular ejection fraction (LVEF) <= 35%, while amiodarone had no effect on survival. There are limited data regarding the influence of gender on outcome of patients receiving ICDs for primary prevention. Methods: We examined gender differences in response to treatment and outcome in this cohort. Results: Women comprised 23% of the SCD-HeFT cohort, with similar percentages in the amiodarone, ICD, and placebo groups. Compared with men, women were more likely to be non-Caucasian, to have class III heart failure, and nonischemic heart disease. After adjustment for baseline differences, overall mortality risk was lower in women than in men. The gender difference in overall mortality was seen in the placebo group, while no gender difference in overall mortality was seen in the ICD group. There was a significantly lower absolute risk of death in the placebo arm women, compared with the placebo arm men (annual mortality rate approximately 4 % vs. 6 %). Conclusions: The impact of ICD therapy appears to differ between men and women in this trial, with a smaller ICD benefit among women. However, the test for an interaction between gender and therapy was not significant. The lower overall mortality risk in women in the placebo group and the smaller number of women enrolled may help to explain why treatment differences in women were much smaller and difficult to detect. C1 [Russo, Andrea M.] Univ Penn, Univ Penn Hlth Syst, Penn Presbyterian Med Ctr, Philadelphia, PA 19104 USA. [Poole, Jeanne E.] Univ Washington, Seattle, WA 98195 USA. [Mark, Daniel B.; Hellkamp, Anne S.; Lee, Kerry L.] Duke Univ, Durham, NC USA. [Anderson, Jill; Johnson, George W.; Bardy, Gust H.] Seattle Inst Cardiac Res, Seattle, WA USA. [Domanski, Michael] NHLBI, Bethesda, MD 20892 USA. RP Russo, AM (reprint author), Univ Penn, Univ Penn Hlth Syst, Penn Presbyterian Med Ctr, 4th Floor PHI,38th & Market St, Philadelphia, PA 19104 USA. EM andrea.russo@uphs.upenn.edu OI Mark, Daniel/0000-0001-6340-8087 NR 30 TC 34 Z9 34 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD JUL PY 2008 VL 19 IS 7 BP 720 EP 724 DI 10.1111/j.1540-8167.2008.01129.x PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 327EA UT WOS:000257711200013 PM 18373605 ER PT J AU Franco, R Panayiotidis, MI De la Paz, LDO AF Franco, Rodrigo Panayiotidis, Mihalis I. De la Paz, Lenin D. Ochoa TI Autocrine signaling involved in cell volume regulation: The role of released transmitters and plasma membrane receptors SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Review ID INDUCED ATP RELEASE; ASCITES TUMOR-CELLS; HUMAN EPITHELIAL-CELLS; PROTEIN-KINASE-C; SMOOTH-MUSCLE-CELLS; SENSITIVE CHLORIDE CHANNELS; SH-SY5Y NEUROBLASTOMA-CELLS; CEREBELLAR GRANULE NEURONS; CULTURED RAT ASTROCYTES; AMINO-ACID RELEASE AB Cell volume regulation is a basic homeostatic mechanism transcendental for the normal physiology and function of cells. It is mediated principally by the activation of osmolyte transport pathways that result in net changes in solute concentration that counteract cell volume challenges in its constancy. This process has been described to be regulated by a complex assortment of intracellular signal transduction cascades. Recently, several studies have demonstrated that alterations in cell volume induce the release of a wide variety of transmitters including hormones, ATP and neurotransmitters, which have been proposed to act as extracellular signals that regulate the activation of cell volume regulatory mechanisms. In addition, changes in cell volume have also been reported to activate plasma membrane receptors (including tyrosine kinase receptors, G-protein coupled receptors and integrins) that have been demonstrated to participate in the regulatory process of cell volume. In this review, we summarize recent studies about the role of changes in cell volume in the regulation of transmitter release as well as in the activation of plasma membrane receptors and their further implications in the regulation of the signaling machinery that regulates the activation of osmolyte flux pathways. We propose that the autocrine regulation of Ca(2+)-dependent and tyrosine phosphorylation-dependent signaling pathways by the activation of plasma membrane receptors and swelling-induced transmitter release is necessary for the activation/regulation of osmolyte efflux pathways and cell volume recovery. Furthermore, we emphasize the importance of studying these extrinsic signals because of their significance in the understanding of the physiology of cell volume regulation and its role in cell biology in vivo, where the constraint of the extracellular space might enhance the autocrine or even paracrine signaling induced by these released transmitters. C1 [Franco, Rodrigo] Univ Nacl Autonoma Mexico, FES Iztacala, Biomed Res Unit, Lab Cell Biol & Signal Transduct, Tlalnepantla 54090, Edo Mexico, Mexico. [Franco, Rodrigo] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. [Panayiotidis, Mihalis I.] Univ Nevada, Sch Publ Hlth, Reno, NV 89557 USA. [De la Paz, Lenin D. Ochoa] Univ Calif Irvine, Sch Biol Sci, Dept Neurobiol & Behav, Irvine, CA 92717 USA. RP Franco, R (reprint author), Univ Nacl Autonoma Mexico, FES Iztacala, Biomed Res Unit, Lab Cell Biol & Signal Transduct, Av Barrios 1, Tlalnepantla 54090, Edo Mexico, Mexico. EM rfranco@campus.iztacala.unam.mx RI Franco, Rodrigo/D-9470-2013; OI Franco, Rodrigo/0000-0003-3241-8615; Panagiotidis, Mihalis/0000-0002-1130-5972 FU Intramural NIH HHS NR 305 TC 24 Z9 24 U1 2 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JUL PY 2008 VL 216 IS 1 BP 14 EP 28 DI 10.1002/jcp.21406 PG 15 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 311LD UT WOS:000256600800003 PM 18300263 ER PT J AU Fukunaga, M Horovitz, SG de Zwart, JA van Gelderen, P Balkin, TJ Braun, AR Duyn, JH AF Fukunaga, Masaki Horovitz, Silvina G. de Zwart, Jacco A. van Gelderen, Peter Balkin, Thomas J. Braun, Allen R. Duyn, Jeff H. TI Metabolic origin of BOLD signal fluctuations in the absence of stimuli SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE BOLD; CMRO2; connectivity; fMRI; resting state; sleep ID CEREBRAL-BLOOD-FLOW; INDEPENDENT COMPONENT ANALYSIS; FUNCTIONAL CONNECTIVITY; OXIDATIVE-METABOLISM; OXYGEN-CONSUMPTION; VISUAL-CORTEX; BASAL GANGLIA; BRAIN; FMRI; OSCILLATIONS AB Blood oxygen level-dependent (BOLD) functional magnetic resonance imaging studies have shown the existence of ongoing blood flow fluctuations in the absence of stimuli. Although this so-called 'resting-state activity' appears to be correlated across brain regions with apparent functional relationship, its origin might be predominantly vascular and not directly representing neuronal signaling. To investigate this, we simultaneously measured BOLD and perfusion signals on healthy human subjects (n = 11) and used their ratio (BOLD/perfusion ratio or BPR) as an indicator of metabolic demand. BPR during rest and sleep was compared with that during a visual task (VT) and a breath-holding task (BH), which are challenges with substantial and little metabolic involvement, respectively. Within the visual cortex, BPR was 3.76 +/- 1.23 during BH, which was significantly higher than during the VT (1.76 +/- 0.27) and rest (1.56 +/- 0.41). Meanwhile, BPR values during VT and rest were not significantly different, suggesting a similar metabolic involvement. Eight subjects showed stage 1 and 2 sleep, during which temporally correlated BOLD and perfusion activity continued. In these subjects, there was no significant difference in BPR between the sleep and waking conditions (1.79 +/- 0.54 and 1.66 +/- 0.67, respectively), but both were lower than the BPR during BH. These data suggest that resting-state activity, at least in part, represents a metabolic process. C1 [Fukunaga, Masaki; Horovitz, Silvina G.; de Zwart, Jacco A.; van Gelderen, Peter; Duyn, Jeff H.] NINDS, Adv MRI, LFMI, Natl Inst Hlth, Bethesda, MD 20892 USA. [Balkin, Thomas J.] Walter Reed Army Inst Res, Dept Behav Biol, Silver Spring, MD USA. [Braun, Allen R.] NIDCD, Language Sect, Voice Speech & Language Branch, Natl Inst Hlth, Bethesda, MD USA. RP Fukunaga, M (reprint author), NINDS, Adv MRI, LFMI, Natl Inst Hlth, 9000 Rockville Pike,MSC 1065,Bldg 10,Room B1D-72, Bethesda, MD 20892 USA. EM fukunagm@mail.nih.gov RI Duyn, Jozef/F-2483-2010 FU Intramural NIH HHS NR 39 TC 52 Z9 52 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUL PY 2008 VL 28 IS 7 BP 1377 EP 1387 DI 10.1038/jcbfm.2008.25 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 318DZ UT WOS:000257073100011 PM 18382468 ER PT J AU Smith, CB Schmidt, KC Bishu, S Channing, MA Bacon, J Burlin, TV Qin, M Liu, ZH Xia, ZY Huang, TJ Vuong, BK Herscovitch, P AF Smith, Carolyn B. Schmidt, Kathleen C. Bishu, Shrinivas Channing, Michael A. Bacon, Jeff Burlin, Thomas V. Qin, Mei Liu, Zhong-hua Xia, Zengyan Huang, Tianjiang Vuong, Bee-Kee Herscovitch, Peter TI Use of acute hyperphenylalaninemia in rhesus monkeys to examine sensitivity and stability of the L-[1-C-11] leucine method for measurement of regional rates of cerebral protein synthesis with PET SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article; Proceedings Paper CT 54th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 02-06, 2007 CL Washington, DC SP Soc Nucl Med DE hyperphenylalaninemia; protein synthesis; leucine; brain; positron emission tomography ID BLOOD-BRAIN-BARRIER; AMINO-ACID-TRANSPORT; SYNTHESIS INVIVO; PHENYLALANINE; TISSUE; PHENYLKETONURIA; DISAGGREGATION; INHIBITION; MECHANISM; MOUSE AB We have previously shown by direct comparison with autoradiographic and biochemical measurements that the L-[1-C-11] leucine positron emission tomography method provides accurate determinations of regional rates of cerebral protein synthesis (rCPS) and the fraction (k) of unlabeled leucine in the precursor pool for protein synthesis derived from arterial plasma. In this study, we examine sensitivity of the method to detect changes in k and stability of the method to measure rCPS in the face of these changes. We studied four isoflurane-anesthetized monkeys dynamically scanned with the high resolution research tomograph under control and mild hyperphenylalaninemic conditions. Hyperphenylalaninemia was produced by an infusion of phenylalanine that increased plasma phenylalanine concentrations three- to five-fold. In phenylalanine-infused monkeys, plasma leucine concentrations remained relatively constant, but values of k were statistically significantly decreased by 11% to 15%; rCPS was unaffected. Effects on k are consistent with competitive inhibition of leucine transport by increased plasma phenylalanine. The effect on k shows that competition for the transporter results in a reduction in the fraction of leucine in the precursor pool for protein synthesis coming from plasma. Even under these hyperphenylalaninemic conditions, rCPS remains unchanged due to the compensating increased contribution of leucine from protein degradation to the precursor pool. C1 [Smith, Carolyn B.; Schmidt, Kathleen C.; Bishu, Shrinivas; Burlin, Thomas V.; Qin, Mei; Liu, Zhong-hua; Xia, Zengyan; Huang, Tianjiang] Natl Inst Mental Hlth, Sect Neuroadaptat & Prot Metab, Bethesda, MD 20892 USA. [Channing, Michael A.; Bacon, Jeff; Vuong, Bee-Kee] NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA. RP Smith, CB (reprint author), Natl Inst Mental Hlth, Sect Neuroadaptat & Prot Metab, Bldg 10,Rm 2D54,10 Ctr Dr, Bethesda, MD 20892 USA. EM beebec@intra.nimh.nih.gov FU Intramural NIH HHS [Z01 MH000889-28] NR 25 TC 2 Z9 2 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUL PY 2008 VL 28 IS 7 BP 1388 EP 1398 DI 10.1038/jcbfm.2008.27 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 318DZ UT WOS:000257073100012 PM 18431402 ER PT J AU Kim, HS Wainer, IW AF Kim, Hee Seung Wainer, Irving W. TI Rapid analysis of the interactions between drugs and human serum albumin (HSA) using high-performance affinity chromatography (HPAC) SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE frontal chromatography; zonal elution; human serum albumin; association constants; drug-protein interaction; affinity chromatography ID PLASMA-PROTEIN BINDING; LIQUID-CHROMATOGRAPHY; LIGAND-BINDING; SITES; DISPLACEMENT; COLUMNS AB This study used a combination of zonal elution and frontal affinity chromatography on immobilized human serum albumin (HSA) high-performance affinity chromatography (HPAC) column to examine the association constants of various compounds that have been studied by equilibrium dialysis or ultra filtration. A standard plot was generated from retention factors of reference compounds using zonal elution chromatography against association constants of reference compounds using frontal affinity chromatography. The linear relationship was established (r(2) = 0.9993) between retention factors and association constants of reference compounds. This standard plot was later used for rapid determination of association constants of various drugs which show low to medium binding affinity to HSA. Association constants of those drugs from this study were compared to that of more generally used methods (i.e., equilibrium dialysis or ultra filtration) from literature and resulted in a relatively high correlation (r(2) = 0.945) value. This combination of zonal elution and frontal affinity chromatography method for determining association constants showed several advantages against traditional methods. Depending on drugs of interest, an association constant of drug to HSA can be measured as fast as 1.5 min. Other notable advantages include an ease of automation and its ability to distinguish association constants of chiral compounds at the same time. The same approach could be used for studying interaction of other drugs and proteins and should further improve overall drug screening process. Published by Elsevier B.V. C1 [Kim, Hee Seung] NIA, Bioanalyt & Drug Discovery Unit, NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Kim, HS (reprint author), NIA, Bioanalyt & Drug Discovery Unit, NIH, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM kimhee@mail.nih.gov FU Intramural NIH HHS [Z01 AG000297-06] NR 27 TC 46 Z9 49 U1 3 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD JUL 1 PY 2008 VL 870 IS 1 BP 22 EP 26 DI 10.1016/j.jchromb.2008.05.029 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 328YV UT WOS:000257835000004 PM 18554995 ER PT J AU Biller, BMK Grossman, AB Stewart, PM Melmed, S Bertagna, X Bertherat, J Buchfelder, M Colao, A Hermus, AR Hofland, LJ Klibanski, A Lacroix, A Lindsay, JR Newell-Price, J Nieman, LK Petersenn, S Sonino, N Stalla, GK Swearingen, B Vance, ML Wass, JAH Boscaro, M AF Biller, B. M. K. Grossman, A. B. Stewart, P. M. Melmed, S. Bertagna, X. Bertherat, J. Buchfelder, M. Colao, A. Hermus, A. R. Hofland, L. J. Klibanski, A. Lacroix, A. Lindsay, J. R. Newell-Price, J. Nieman, L. K. Petersenn, S. Sonino, N. Stalla, G. K. Swearingen, B. Vance, M. L. Wass, J. A. H. Boscaro, M. TI Treatment of adrenocorticotropin-dependent Cushing's syndrome: A consensus statement SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID PPAR-GAMMA RECEPTOR; TERM-FOLLOW-UP; BILATERAL LAPAROSCOPIC ADRENALECTOMY; SOMATOSTATIN ANALOG SMS-201-995; GROWTH-HORMONE-SECRETION; TRANS-SPHENOIDAL SURGERY; TRANSSPHENOIDAL SURGERY; NELSONS-SYNDROME; PITUITARY IRRADIATION; MEDICAL THERAPY AB Objective: Our objective was to evaluate the published literature and reach a consensus on the treatment of patients with ACTH-dependent Cushing's syndrome, because there is no recent consensus on the management of this rare disorder. Participants: Thirty-two leading endocrinologists, clinicians, and neurosurgeons with specific expertise in the management of ACTH-dependent Cushing's syndrome representing nine countries were chosen to address 1) criteria for cure and remission of this disorder, 2) surgical treatment of Cushing's disease, 3) therapeutic options in the event of persistent disease after transsphenoidal surgery, 4) medical therapy of Cushing's disease, and 5) management of ectopic ACTH syndrome, Nelson's syndrome, and special patient populations. Evidence: Participants presented published scientific data, which formed the basis of the recommendations. Opinion shared by a majority of experts was used where strong evidence was lacking. Consensus Process: Participants met for 2 d, during which there were four chaired sessions of presentations, followed by general discussion where a consensus was reached. The consensus statement was prepared by a steering committee and was then reviewed by all authors, with suggestions incorporated if agreed upon by the majority. Conclusions: ACTH-dependent Cushing's syndrome is a heterogeneous disorder requiring a multidisciplinary and individualized approach to patient management. Generally, the treatment of choice for ACTH-dependent Cushing's syndrome is curative surgery with selective pituitary or ectopic corticotroph tumor resection. Second-line treatments include more radical surgery, radiation therapy (for Cushing's disease), medical therapy, and bilateral adrenalectomy. Because of the significant morbidity of Cushing's syndrome, early diagnosis and prompt therapy are warranted. C1 [Biller, B. M. K.; Klibanski, A.; Swearingen, B.] Massachusetts Gen Hosp, Neuroendocrine Clin Ctr, Boston, MA 02114 USA. [Grossman, A. B.] St Bartholomews Hosp, Dept Endocrinol, London EC1A 7BE, England. [Stewart, P. M.] Univ Birmingham, Queen Elizabeth Hosp, Div Med Sci, Birmingham B29 6JD, W Midlands, England. [Melmed, S.] Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA. [Bertagna, X.; Bertherat, J.] Hop Cochin, Dept Endocrinol, Fac Med Paris Descartes, AP HP, F-75014 Paris, France. [Buchfelder, M.] Univ Erlangen Nurnberg, Neurochirurg Klin, D-91054 Erlangen, Germany. [Colao, A.] Univ Naples Federico II, Dipartimento Endocrinol & Oncol Mol & Clin, I-80131 Naples, Italy. [Hermus, A. R.] Univ Med Ctr Nijmegen, Dept Endocrinol, NL-6000500 Nijmegen, Netherlands. [Hofland, L. J.] Erasmus MC, Div Endocrinol, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands. [Lacroix, A.] Univ Montreal, Ctr Hosp, Dept Med, Div Endocrinol, Montreal, PQ H2W 1T8, Canada. [Newell-Price, J.] Univ Sheffield, Sch Med, Sheffield S10 2TN, S Yorkshire, England. [Nieman, L. K.] NIH, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. [Petersenn, S.] Univ Essen Gesamthsch, Div Endocrinol, D-45122 Essen, Germany. [Sonino, N.] Univ Padua, Dept Stat Sci, I-35122 Padua, Italy. [Stalla, G. K.] Max Planck Inst Psychiat, Dept Endocrinol, D-80804 Munich, Germany. [Vance, M. L.] Univ Virginia Hlth Syst, Charlottesville, VA 22903 USA. [Wass, J. A. H.] Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Dept Endocrinol, Oxford OX3 7LJ, England. [Boscaro, M.] Polytech Univ Marche, Div Endocrinol, Inst Internal Med, I-60126 Ancona, Italy. RP Boscaro, M (reprint author), Polytech Univ Marche, Sch Med, Div Endocrinol, Inst Internal Med, I-60020 Ancona, Italy. EM m.boscaro@univpm.it RI Hermus, A.R.M.M./H-8043-2014; OI BOSCARO, MARCO/0000-0003-2596-1652 FU Intramural NIH HHS [Z01 HD008833-02] NR 107 TC 377 Z9 397 U1 1 U2 16 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL 1 PY 2008 VL 93 IS 7 BP 2454 EP 2462 DI 10.1210/jc.2007-2734 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 324JA UT WOS:000257513700006 PM 18413427 ER PT J AU Peter, I Kelley-Hedgepeth, A Fox, CS Cupples, LA Huggins, GS Housman, DE Karas, RH Mendelsohn, ME Levy, D Murabito, JM AF Peter, Inga Kelley-Hedgepeth, Alyson Fox, Caroline S. Cupples, L. Adrienne Huggins, Gordon S. Housman, David E. Karas, Richard H. Mendelsohn, Michael E. Levy, Daniel Murabito, Joanne M. TI Variation in estrogen-related genes associated with cardiovascular phenotypes and circulating estradiol, testosterone, and dehydroepiandrosterone sulfate levels SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID RECEPTOR-ALPHA GENE; CORONARY-ARTERY-DISEASE; LOW SERUM TESTOSTERONE; LEFT-VENTRICULAR MASS; MIDDLE-AGED MEN; MYOCARDIAL-INFARCTION; POSTMENOPAUSAL WOMEN; ANGIOGRAPHIC EXTENT; HEART-DISEASE; SEX-HORMONES AB Background: Younger age at the onset of menopause and lower circulating levels of estrogen are risk factors for cardiovascular disease. Several studies have detected associations between variations in genes encoding estrogen receptors alpha (ESR1) and beta (ESR2), and enzyme aromatase (CYP19A1), which regulates the estrogen to testosterone ratio, and cardiovascular phenotypes in the Framingham Heart Study. To explore potential mechanisms by which these gene variants may contribute to cardiovascular disease, we tested the hypothesis that the polymorphisms were associated with endogenous steroid hormone levels. Methods: Multiple regression analysis was used to assess the relation between reported polymorphisms and total serum estradiol, testosterone, and dehydroepiandrosterone sulfate levels in 834 men and 687 women who attended the third and fourth Framingham Heart Study examination cycles. Results: In men, significant associations were detected between CYP19A1 polymorphisms and estradiol and testosterone levels, and the estradiol to testosterone ratio (P ranges 0.0005-0.01). Specifically, carriers of common haplotype rs700518[G]-(TTTA)(n) [L]-rs726547[ C] had higher estradiol levels (5% per copy; P = 0.0004), lower testosterone levels (17% per copy; P = 0.036), and a higher estradiol to testosterone ratio (24% per copy; P < 0.0001) compared with the rs700518[ A]( TTTA) n [ S]-rs726547[C] carriers. In addition, postmenopausal carriers of the ESR2 ( CA) n long allele and rs1256031[C] allele had moderately higher estradiol levels ( P <= 0.03). No significant associations with the ESR1 variants were detected. Conclusions: Our findings suggest that variations in CYP19A1 correlate with steroid hormone levels in men. Knowledge that a specific carrier status may predispose to altered steroid hormone levels may lead to targeted intervention strategies to reduce health risks in genetically susceptible individuals. C1 [Peter, Inga] Tufts Med Ctr, Ctr Genet Epidemiol & Modeling, Inst Clin Res & Hlth Policy Studies, Boston, MA 02111 USA. [Kelley-Hedgepeth, Alyson; Huggins, Gordon S.; Karas, Richard H.; Mendelsohn, Michael E.] Tufts Med Ctr, Mol Cardiol Res Inst, Boston, MA 02111 USA. [Housman, David E.] MIT, Ctr Canc Res, Cambridge, MA 02139 USA. [Fox, Caroline S.; Levy, Daniel; Murabito, Joanne M.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Levy, Daniel; Murabito, Joanne M.] Boston Univ, Sch Med, Dept Prevent Med & Cardiol, Gen Internal Med Sect, Boston, MA 02118 USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. RP Peter, I (reprint author), Tufts Med Ctr, Ctr Genet Epidemiol & Modeling, Inst Clin Res & Hlth Policy Studies, 800 Washington St,Box 63, Boston, MA 02111 USA. EM ipeter@tuftsmedicalcenter.org OI Cupples, L. Adrienne/0000-0003-0273-7965; Murabito, Joanne/0000-0002-0192-7516 FU NHLBI NIH HHS [HL 069770, P01 HL077378, T32 HL069770, HL 077378] NR 40 TC 24 Z9 24 U1 0 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 JUL 1 PY 2008 VL 93 IS 7 BP 2779 EP 2785 DI 10.1210/jc.2008-0106 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 324JA UT WOS:000257513700055 PM 18445666 ER PT J AU Chen, WM Erdos, MR Jackson, AU Saxena, R Sanna, S Silver, KD Timpson, NJ Hansen, T Orru, M Piras, MG Bonnycastle, LL Willer, CJ Lyssenko, V Shen, HQ Kuusisto, J Ebrahim, S Sestu, N Duren, WL Spada, MC Stringham, HM Scott, LJ Olla, N Swift, AJ Najjar, S Mitchell, BD Lawlor, DA Smith, GD Ben-Shlomo, Y Andersen, G Borch-Johnsen, K Jorgensen, T Saramies, J Valle, TT Buchanan, TA Shuldiner, AR Lakatta, E Bergman, RN Uda, M Tuomilehto, J Pedersen, O Cao, A Groop, L Mohlke, KL Laakso, M Schlessinger, D Collins, FS Altshuler, D Abecasis, GR Boehnke, M Scuteri, A Watanabe, RM AF Chen, Wei-Min Erdos, Michael R. Jackson, Anne U. Saxena, Richa Sanna, Serena Silver, Kristi D. Timpson, Nicholas J. Hansen, Torben Orru, Marco Piras, Maria Grazia Bonnycastle, Lori L. Willer, Cristen J. Lyssenko, Valeriya Shen, Haiqing Kuusisto, Johanna Ebrahim, Shah Sestu, Natascia Duren, William L. Spada, Maria Cristina Stringham, Heather M. Scott, Laura J. Olla, Nazario Swift, Amy J. Najjar, Samer Mitchell, Braxton D. Lawlor, Debbie A. Smith, George Davey Ben-Shlomo, Yoav Andersen, Gitte Borch-Johnsen, Knut Jorgensen, Torben Saramies, Jouko Valle, Timo T. Buchanan, Thomas A. Shuldiner, Alan R. Lakatta, Edward Bergman, Richard N. Uda, Manuela Tuomilehto, Jaakko Pedersen, Oluf Cao, Antonio Groop, Leif Mohlke, Karen L. Laakso, Markku Schlessinger, David Collins, Francis S. Altshuler, David Abecasis, Goncalo R. Boehnke, Michael Scuteri, Angelo Watanabe, Richard M. TI Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID SUBUNIT-RELATED PROTEIN; OLD ORDER AMISH; DEPENDENT DIABETES-MELLITUS; BETA-CELL FUNCTION; SALT EXPORT PUMP; WIDE ASSOCIATION; GLUCOKINASE GENE; GLUCOSE-6-PHOSPHATASE-RELATED PROTEIN; INSULIN-RESISTANCE; PANCREATIC-ISLETS AB Identifying the genetic variants that regulate fasting glucose concentrations may further our understanding of the pathogenesis of diabetes. We therefore investigated the association of fasting glucose levels with SNPs in 2 genomewide scans including a total of 5,088 nondiabetic individuals from Finland and Sardinia. We found a significant association between the SNP rs563694 and fasting glucose concentrations (P = 3.5 x 10(-7)). This association was further investigated in an additional 18,436 nondiabetic individuals of mixed European descent from 7 different studies. The combined P value for association in these follow-up samples was 6.9 x 10(-26), and combining results from all studies resulted in an overall P value for association of 6.4 x 10(-33). Across these studies, fasting glucose concentrations increased 0.01-0.16 mM with each copy of the major allele, accounting for approximately 1% of the total variation in fasting glucose. The rs563694 SNP is located between the genes glucose-6-phosphatase catalytic subunit 2 (G6PC2) and ATP-binding cassette, subfamily B (MDR/TAP), member 11 (ABCB11). Our results in combination with data reported in the literature suggest that G6PC2, a glucose-6-phosphatase almost exclusively expressed in pancreatic islet cells, may underlie variation in fasting glucose, though it is possible that ABCB11, which is expressed primarily in liver, may also contribute to such variation. C1 [Scuteri, Angelo] Ist Nazl Ricovero E Cura Anziari, Unita Operat Geriatria, Rome, Italy. [Chen, Wei-Min] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA. [Chen, Wei-Min] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Erdos, Michael R.; Bonnycastle, Lori L.; Swift, Amy J.; Collins, Francis S.] NHGRI, Genome Technol Branch, Bethesda, MD USA. [Jackson, Anne U.; Sanna, Serena; Willer, Cristen J.; Duren, William L.; Stringham, Heather M.; Scott, Laura J.; Abecasis, Goncalo R.; Boehnke, Michael] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Jackson, Anne U.; Sanna, Serena; Willer, Cristen J.; Duren, William L.; Stringham, Heather M.; Scott, Laura J.; Abecasis, Goncalo R.; Boehnke, Michael] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Saxena, Richa; Altshuler, David] MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02139 USA. [Saxena, Richa; Altshuler, David] Harvard Univ, Cambridge, MA 02138 USA. [Sanna, Serena; Piras, Maria Grazia; Spada, Maria Cristina; Olla, Nazario; Uda, Manuela; Cao, Antonio] CNR, Ist Neurogenet & Neurofarmacol, Cagliari, Italy. [Silver, Kristi D.; Shen, Haiqing; Mitchell, Braxton D.; Shuldiner, Alan R.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [Timpson, Nicholas J.; Lawlor, Debbie A.; Smith, George Davey] Univ Bristol, Dept Social Med, MRC, Ctr Causal Analy Translat Epidemiol, Bristol, Avon, England. [Hansen, Torben; Andersen, Gitte; Borch-Johnsen, Knut; Pedersen, Oluf] Steno Diabet Ctr, DK-2820 Gentofte, Denmark. [Lyssenko, Valeriya; Groop, Leif] Lund Univ, Malmo Univ Hosp, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden. [Kuusisto, Johanna; Laakso, Markku] Univ Kuopio, Dept Med, SF-70210 Kuopio, Finland. [Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Ebrahim, Shah] Univ London, London Sch Hyg & Trop Med, Noncommunicable Dis Epidemiol Unit, Dept Epidemiol & Populat Hlth, London, England. [Sestu, Natascia; Najjar, Samer; Lakatta, Edward; Schlessinger, David] NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. [Borch-Johnsen, Knut; Jorgensen, Torben] Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark. [Borch-Johnsen, Knut; Pedersen, Oluf] Univ Aarhus, Fac Hlth Sci, Aarhus, Denmark. [Saramies, Jouko] Savitaipale Hlth Ctr, Savitaipale, Finland. [Valle, Timo T.; Tuomilehto, Jaakko] Univ Helsinki, Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Diabet Unit, Helsinki, Finland. [Valle, Timo T.; Tuomilehto, Jaakko] Univ Helsinki, Dept Publ Hlth, Helsinki, Finland. [Buchanan, Thomas A.] Univ So Calif, Dept Med, Div Endocrinol, Los Angeles, CA USA. [Buchanan, Thomas A.; Bergman, Richard N.; Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA. [Tuomilehto, Jaakko] S Ostrobothnia Cent Hosp, Senajoki, Finland. [Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Scuteri, Angelo] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. RP Scuteri, A (reprint author), Ist Nazl Ricovero E Cura Anziari, Unita Operat Geriatria, Rome, Italy. EM angeloelefante@interfree.it; rwatanab@usc.edu RI Chen, Wei-Min/A-8469-2009; Abecasis, Goncalo/B-7840-2010; Altshuler, David/A-4476-2009; Fox, Laura /C-6249-2016; Davey Smith, George/A-7407-2013; OI Mitchell, Braxton/0000-0003-4920-4744; Timpson, Nicholas/0000-0002-7141-9189; Altshuler, David/0000-0002-7250-4107; Davey Smith, George/0000-0002-1407-8314; sanna, serena/0000-0002-3768-1749; Monsalve, Beatriz Elena/0000-0002-5994-866X; Abecasis, Goncalo/0000-0003-1509-1825; piras, maria grazia/0000-0001-9004-0900; Jorgensen, Torben/0000-0001-9453-2830; Lawlor, Debbie A/0000-0002-6793-2262 FU British Heart Foundation; Department of Health; Intramural NIH HHS; Medical Research Council [G0600705, G9824960]; NCRR NIH HHS [M01 RR 16500, M01 RR000052, M01 RR016500]; NHGRI NIH HHS [Z01 HG000024]; NHLBI NIH HHS [R01 HL069313, R01 HL69313, U01 HL072515, U01 HL72515]; NIA NIH HHS [N01-AG-1-2109, R01 AG018728, R01 AG18728]; NIDA NIH HHS [U54 DA021519]; NIDDK NIH HHS [P30 DK072488, DK062370, DK062418, DK069922, DK072193, P30 DK079637, R01 DK029867, R01 DK062370, R01 DK068495, R01 DK069922, R01 DK072193, R01 DK54361, R56 DK062370, U01 DK062370, U01 DK062418] NR 68 TC 103 Z9 105 U1 0 U2 4 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 JUL PY 2008 VL 118 IS 7 BP 2620 EP 2628 DI 10.1172/JCI34566 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 326KL UT WOS:000257657400029 PM 18521185 ER PT J AU Burbelo, PD Ramanathan, R Klion, AD Iadarola, MJ Nutman, TB AF Burbelo, Peter D. Ramanathan, Roshan Klion, Amy D. Iadarola, Michael J. Nutman, Thomas B. TI Rapid, novel, specific, high-throughput assay for diagnosis of Loa loa infection SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE-CHAIN-REACTION; HUMAN OCCULT LOIASIS; WUCHERERIA-BANCROFTI; ONCHOCERCIASIS; ANTIGEN; FILARIASIS; RECOGNITION; IVERMECTIN; IMMUNITY; SAMPLES AB The ability to diagnose Loa loa infection readily and accurately remains a demanding task. Among the available diagnostic methods, many are impractical for point-of-care field testing. To investigate whether luciferase immunoprecipitation systems (LIPS) can be used for rapid and specific diagnosis of L. loa infection, a LIPS assay was developed based on immunoglobulin G (IgG) and IgG4 subclass antibodies to a recombinant L. loa SXP-1 (designated LlSXP-1) antigen and tested with sera from healthy controls or patients with proven infection with L. loa, Mansonella perstans, Onchocerca volvulus, Strongyloides stercoralis, or Wuchereria bancrofti. A LIPS test measuring IgG antibody against LlSXP-1 readily differentiated L. loa-infected from uninfected patients and demonstrated markedly improved sensitivity and specificity compared with an LlSXP-1 IgG4-based enzyme-linked immunosorbent assay (67% sensitivity and 99% specificity). No significant immunoreactivity was observed with S. stercoralis-infected sera, but a small number of patients infected with O. volvulus, M. perstans, or W. bancrofti showed positive immunoreactivity. Measuring anti-IgG4-specific antibodies to LlSXP-1 showed a significant correlation (r similar to 0.85; P < 0.00001) with the anti-IgG results but showed no advantage over measuring the total IgG response alone. In contrast, a rapid LIPS format (called QLIPS) in which the tests are performed in less than 15 minutes under nonequilibrium conditions significantly improved the specificity for cross-reactive O. volvulus patient sera (100% sensitivity and 100% specificity). These results suggest that LIPS (and the even more rapid test QLIPS) represents a major advance in the ability to diagnose L. loa infection and may have future applications for point-of-care diagnostics. C1 [Ramanathan, Roshan; Klion, Amy D.; Nutman, Thomas B.] NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. [Burbelo, Peter D.; Iadarola, Michael J.] Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, Bethesda, MD 20892 USA. RP Nutman, TB (reprint author), NIH, Parasit Dis Lab, Bldg 4,Room B1-03,4 Ctr Dr, Bethesda, MD 20892 USA. EM tnutman@niaid.nih.gov OI Klion, Amy/0000-0002-4986-5326 FU Division of Intramural Research; National Institutes of Allergy and Infectious Diseases; National Institute of Dental and Craniofacial Research FX This work was supported in part by the Division of Intramural Research, National Institutes of Allergy and Infectious Diseases, and National Institute of Dental and Craniofacial Research. We thank Nancy Shulman for editorial assistance. Informed consent was obtained from all patients in accordance with the human experimentation guidelines of the Department of Health and Human Services under several NIAID IRB-approved protocols. NR 22 TC 37 Z9 38 U1 0 U2 5 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 JUL PY 2008 VL 46 IS 7 BP 2298 EP 2304 DI 10.1128/JCM.00490-08 PG 7 WC Microbiology SC Microbiology GA 344DS UT WOS:000258906800023 PM 18508942 ER PT J AU Witebsky, FG Conville, PS Wallace, RJ Brown-Elliott, BA AF Witebsky, Frank G. Conville, Patricia S. Wallace, Richard J., Jr. Brown-Elliott, Barbara A. TI Nocardia cyriacigeorgica - an established rather than an emerging pathogen SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Letter ID ASTEROIDES C1 [Wallace, Richard J., Jr.; Brown-Elliott, Barbara A.] Univ Texas Hlth Ctr Tyler, Dept Microbiol, Tyler, TX 75710 USA. [Witebsky, Frank G.; Conville, Patricia S.] NIH, Microbiol Serv, Dept Lab Med, Warren G Magnuson Clin Ctr,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Witebsky, FG (reprint author), NIH, Microbiol Serv, Dept Lab Med, Warren G Magnuson Clin Ctr,Dept Hlth & Human Serv, Bldg 10, Bethesda, MD 20892 USA. EM pconville@nih.gov NR 4 TC 3 Z9 3 U1 0 U2 2 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 JUL PY 2008 VL 46 IS 7 BP 2469 EP 2469 DI 10.1128/JCM.00510-08 PG 1 WC Microbiology SC Microbiology GA 344DS UT WOS:000258906800062 PM 18614666 ER PT J AU Warren, JL Mariotto, AB Meekins, A Topor, M Brown, ML AF Warren, Joan L. Mariotto, Angela B. Meekins, Angela Topor, Marie Brown, Martin L. TI Current and future utilization of services from medical oncologists SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ADJUVANT CHEMOTHERAPY; BREAST-CANCER; OLDER WOMEN; CARE; POPULATION; GENERALIZABILITY; OUTCOMES; THERAPY AB Purpose There is limited information on the current use of oncologists and projections of future need. This analysis assesses current utilization patterns and projects the number of people with cancer and their use of oncologists' services through 2020. Methods Data from the Surveillance, Epidemiology, and End Results cancer registries and Medicare physician claims were used to estimate oncologists' services from 1998 to 2003. We estimated the portion of patients with cancer who saw an oncologist, the mean number of visits, and the clinical setting where care was provided. Care was divided into initial, continuing, and last-year-of-life phases. Projections for future number of patients with cancer and visits were calculated by applying incidence and prevalence rates derived from Surveillance, Epidemiology, and End Results data to census population projections through 2020. Results The percentage of patients who saw an oncologist was 47% during the initial-care phase, 36% during the continuing-care phase, and 70% in the last year of life. The number of visits varied by age, sex, cancer site, and phase. The total number of cancer patients in the United States is projected to increase 55%, from 11.8 million in 2005 to 18.2 million in 2020. Total oncology visits are projected to increase from 38 million in 2005 to 57 million in 2020. Conclusion Utilization of oncologists' services will increase appreciably between 2005 and 2020; this will be driven predominantly by an increase in survivors of cancer and by the aging of the population. The United States may face an acute shortage of medical oncologists if efforts are not taken to meet this growing need. C1 NCI, Hlth Serv & Econ Branch Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Surveillance Res Program, Bethesda, MD 20892 USA. Informat Management Serv Inc, Silver Spring, MD USA. RP Warren, JL (reprint author), NCI, Hlth Serv & Econ Branch Appl Res Program, Div Canc Control & Populat Sci, Executive Pl N,Rm 4005,6130 Executive Blvd,MSC 73, Bethesda, MD 20892 USA. EM joan_warren@nih.gov NR 19 TC 50 Z9 51 U1 3 U2 4 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 JUL 1 PY 2008 VL 26 IS 19 BP 3242 EP 3247 DI 10.1200/JCO.2007.14.6357 PG 6 WC Oncology SC Oncology GA 323AM UT WOS:000257416400022 PM 18591559 ER PT J AU Bernstein, WB Kemp, JD Kim, GS Johnson, VV AF Bernstein, Wendy B. Kemp, Jean D. Kim, Geoffrey S. Johnson, Viviana V. TI Diagnosing leptomeningeal carcinomatosis with negative CSF cytology in advanced prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID INTRACRANIAL METASTASES; NEOPLASTIC MENINGITIS; BRAIN METASTASIS; SOLID TUMORS; EXPERIENCE; FEATURES C1 [Bernstein, Wendy B.] Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA. [Johnson, Viviana V.] Natl Naval Med Ctr, Dept Pathol, Bethesda, MD USA. NCI, Med Oncol Branch, Bethesda, MD 20892 USA. RP Bernstein, WB (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med, Room A3060, Bethesda, MD 20814 USA. NR 20 TC 8 Z9 8 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 JUL 1 PY 2008 VL 26 IS 19 BP 3281 EP 3284 DI 10.1200/JCO.2008.16.4533 PG 5 WC Oncology SC Oncology GA 323AM UT WOS:000257416400028 PM 18591564 ER PT J AU Stinson, FS Dawson, DA Goldstein, RB Chou, SP Huang, B Smith, SM Ruan, WJ Pulay, AJ Saha, TD Pickering, RP Grant, BF AF Stinson, Frederick S. Dawson, Deborah A. Goldstein, Rise B. Chou, S. Patricia Huang, Boji Smith, Sharon M. Ruan, W. June Pulay, Attila J. Saha, Tulshi D. Pickering, Roger P. Grant, Bridget F. TI Prevalence, correlates, disability, and comorbidity of DSM-IV narcissistic personality disorder: Results from the Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID AXIS-II COMORBIDITY; INTERVIEW SCHEDULE AUDADIS; GENERAL-POPULATION SAMPLE; PSYCHIATRIC DIAGNOSTIC MODULES; MAJOR DEPRESSIVE DISORDER; SUBSTANCE USE DISORDERS; UNITED-STATES; ANXIETY DISORDER; PANIC DISORDER; DRUG MODULES AB Objectives: To present nationally representative findings on prevalence, sociodemographic correlates, disability, and comorbidity of narcissistic personality disorder (NPD) among men and women. Method: Face-to-face interviews with 34,653 adults participating in the Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions conducted between 2004 and 2005 in the United States. Results: Prevalence of lifetime NPD was 6.2%, with rates greater for men (7.7%) than for women (4.8%). NPD was significantly more prevalent among black men and women and Hispanic women, younger adults, and separated/divorced/widowed and never married adults. NPD was associated with mental disability among men but not women. High co-occurrence rates of substance use, mood, and anxiety disorders and other personality disorders were observed. With additional comorbidity controlled for, associations with bipolar I disorder, post-traumatic stress disorder, and schizotypal and borderline personality disorders remained significant, but weakened, among men and women. Similar associations were observed between NPD and specific phobia, generalized anxiety disorder, and bipolar II disorder among women and between NPD and alcohol abuse, alcohol dependence, drug dependence, and histrionic and obsessive-compulsive personality disorders among men. Dysthymic disorder was significantly and negatively associated with NPD. Conclusions: NPD is a prevalent personality disorder in the general U.S. population and is associated with considerable disability among men, whose rates exceed those of women. NPD may not be as stable as previously recognized or described in the DSM-IV. The results highlight the need for further research from numerous perspectives to identify the unique and common genetic and environmental factors underlying the disorder-specific associations with NPD observed in this study. C1 [Stinson, Frederick S.; Dawson, Deborah A.; Goldstein, Rise B.; Chou, S. Patricia; Huang, Boji; Smith, Sharon M.; Ruan, W. June; Pulay, Attila J.; Saha, Tulshi D.; Pickering, Roger P.; Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA. RP Grant, BF (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, MS 9304,5635 Fishers Lane, Bethesda, MD 20892 USA. EM bgrant@willco.niaaa.nih.gov RI Pulay, Attila/B-6155-2011; OI Goldstein, Rise/0000-0002-9603-9473 FU Intramural NIH HHS [Z01 AA000449-04, Z99 AA999999] NR 84 TC 130 Z9 130 U1 5 U2 20 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUL PY 2008 VL 69 IS 7 BP 1033 EP 1045 PG 15 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 331JE UT WOS:000258007700001 PM 18557663 ER PT J AU Bonne, O Vythilingam, M Inagaki, M Wood, S Neumeister, A Nugent, AC Snow, J Luckenbaugh, DA Bain, EE Drevets, WC Charney, DS AF Bonne, Omer Vythilingam, Meena Inagaki, Masatoshi Wood, Suzanne Neumeister, Alexander Nugent, Allison C. Snow, Joseph Luckenbaugh, David A. Bain, Earle E. Drevets, Wayne C. Charney, Dennis S. TI Reduced posterior hippocampal volume in posttraumatic stress disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID BDNF MESSENGER-RNA; DORSAL HIPPOCAMPUS; PSYCHOMETRIC PROPERTIES; BRAIN; MEMORY; DEPRESSION; ISCHEMIA; PTSD; VULNERABILITY; METAANALYSIS AB Objective: Hippocampal volume is reduced in posttraumatic stress disorder (PTSD). In the we sought to determine whether present study, volume loss is homogenously distributed or confined to a certain part of the structure. Method: Twenty-two adult outpatients with PTSD (11 after prolonged prepubertal trauma single adult trauma) and 22 matched and 11 after. healthy subjects were scanned at the National Institute of Mental Health using high-resolution 3T magnetic resonance imaging between September 2003 and August 2004. PTSD diagnosis was conferred using the Structured Clinical Interview for DSM-IV. Volumes of whole, anterior, and posterior hippocampus and subiculum were compared between groups. Results: Total hippocampal volume was lower in patients with PTSD (p = .02), with a significant diagnosis by hippocampal-subregion interaction (p = .02). Post hoc analysis revealed significantly smaller posterior hippocampi in PTSD (p = .006) with no difference in the volumes of anterior hippocampus or subiculum. No volume differences were found between PTSD participants with prolonged childhood abuse compared to single adult trauma exposure. Conclusions: The posterior hippocampus has been associated with storage, processing, and retrieval of spatiotemporal memories, central to the protective function of fear conditioning. Volume deficit in the posterior hippocampus may indicate malfunction in this faculty, leading to the exaggerated conditioned fear response observed in PTSD. C1 [Bonne, Omer] Hadassah Hebrew Univ, Med Ctr, Dept Psychiat, IL-91120 Jerusalem, Israel. [Vythilingam, Meena; Snow, Joseph; Luckenbaugh, David A.] NIMH, Sect Expt Therapeut & Pathophysiol, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. [Inagaki, Masatoshi; Wood, Suzanne; Nugent, Allison C.; Bain, Earle E.; Drevets, Wayne C.] NIMH, Sect Neuroimaging Mood & Anxiety Disorders, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. [Neumeister, Alexander] Yale Univ, Sch Med, Clin Neurosci Div, New Haven, CT USA. [Charney, Dennis S.] Mt Sinai Sch Med, Dept Psychiat Neurosci, New York, NY USA. [Charney, Dennis S.] Mt Sinai Sch Med, Dept Pharmacol & Biol Chem, New York, NY USA. RP Bonne, O (reprint author), Hadassah Hebrew Univ, Med Ctr, Dept Psychiat, POB 12000, IL-91120 Jerusalem, Israel. EM bonne@hadassah.org.il OI Nugent, Allison/0000-0003-2569-2480 FU Intramural NIH HHS [Z01 MH002789-05] NR 44 TC 60 Z9 69 U1 0 U2 9 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUL PY 2008 VL 69 IS 7 BP 1087 EP 1091 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 331JE UT WOS:000258007700007 PM 18572983 ER PT J AU Hatzenbuehler, ML Keyes, KM Narrow, WE Grant, BE Hasin, DS AF Hatzenbuehler, Mark L. Keyes, Katherine M. Narrow, William E. Grant, Bridget E. Hasin, Deborah S. TI Racial/ethnic disparities in service utilization for individuals with co-occurring mental health and substance use disorders in the general population: Results from the National Epidemiologic Survey on Alcohol and Related Conditions SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID DSM-IV ALCOHOL; INTERVIEW SCHEDULE AUDADIS; COMORBIDITY SURVEY REPLICATION; UNITED-STATES; III-R; PSYCHIATRIC-DISORDERS; MAJOR DEPRESSION; DRUG MODULES; NOSOLOGICAL COMPARISONS; DIAGNOSTIC INTERVIEW AB Objective: This study sought to determine whether black/white disparities in service utilization for mental health and substance use disorders persist or are diminished among individuals with psychiatric comorbidity in the general population. Method: The 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions was used to identify individuals with lifetime co-occurring substance use disorders and mood/anxiety disorders (N = 4250; whites, N = 3597; blacks, N = 653). Lifetime service utilization for problems with mood, anxiety, alcohol, and drugs was assessed. Results: Compared to whites, blacks with co-occurring mood or anxiety and substance use disorders were significantly less likely to receive services for mood or anxiety disorders, equally likely to receive services for alcohol use disorders, and more likely to receive some types of services for drug use disorders. Regardless of race/ethnicity, individuals with these co-occurring disorders were almost twice as likely to use services for mood/anxiety disorders than for substance use disorders. Conclusion: Despite the fact that comorbidity generally increases the likelihood of service use, black/white disparities in service utilization among an all-comorbid sample were found, although these disparities differed by type of disorder. Further research is warranted to understand the factors underlying these differences. Prevention and intervention strategies are needed to address the specific mental health needs of blacks with co-occurring disorders, as well as the overall lack of service use for substance use disorders among individuals with co-occurring psychiatric conditions. C1 [Hasin, Deborah S.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. [Hatzenbuehler, Mark L.] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [Hatzenbuehler, Mark L.; Keyes, Katherine M.; Hasin, Deborah S.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Keyes, Katherine M.; Hasin, Deborah S.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. [Narrow, William E.] Amer Psychiat Inst Res & Educ, Arlington, VA USA. [Grant, Bridget E.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD USA. RP Hasin, DS (reprint author), Columbia Univ, NYSPI, 1051 Riverside Dr,Box 123, New York, NY 10032 USA. EM dsh2@columbia.edu FU Intramural NIH HHS [Z01 AA000449-04]; NIAAA NIH HHS [K05 AA014223]; NIDA NIH HHS [R01 DA018652] NR 84 TC 48 Z9 48 U1 5 U2 8 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUL PY 2008 VL 69 IS 7 BP 1112 EP 1121 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 331JE UT WOS:000258007700011 PM 18517286 ER PT J AU Furey, ML Ricciardi, E Schapiro, MB Rapoport, SI Pietrini, P AF Furey, Maura L. Ricciardi, Emiliano Schapiro, Mark B. Rapoport, Stanley I. Pietrini, Pietro TI Cholinergic enhancement eliminates modulation of neural activity by task difficulty in the prefrontal cortex during working memory SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID CEREBRAL-BLOOD-FLOW; EVENT-RELATED FMRI; AGE-RELATED-CHANGES; CAT VISUAL-CORTEX; BRAIN ACTIVATION; PERFORMANCE; STIMULATION; EFFICIENCY; ATTENTION; SYSTEMS AB Previously, we demonstrated that enhancing cholinergic activity during a working memory (WM) task improves performance and reduces blood flow in the right anterior middle/superior frontal cortex, an area known to be important for WM. The purpose of this study was to evaluate the interaction between WM task demands and cholinergic enhancement on neural responses in the prefrontal cortex. Regional cerebral blood flow (rCBF) was measured using H-2 O-15 and positron emission tomography, as 10 young healthy volunteers performed a parametrically varied match-to-sample WM for faces task. For each item, a picture of a face was presented, followed by a delay (1, 6, 11, or 16 sec), then by the presentation of two faces. Subjects were instructed to identify which face they previously had seen. For control items, nonsense pictures were presented in the same spatial and temporal manner. All conditions were performed during an intravenous infusion of saline and physostigmine (1 mg/hr). Subjects were blind to the substance being infused. Reaction time increased significantly with WM delay, and physostigmine decreased reaction time across delay conditions. Significant task-related rCBF increases during saline infusion were seen in superior frontal, middle frontal, and inferior frontal regions, and the response magnitudes in the regions increased systematically with task difficulty. In all of these prefrontal regions, physostigmine administration significantly reduced rCBF during task, particularly at longer task delays, so that no correlation between task delay and rCBF was observed. In the ventral visual cortex, physostigmine increased rCBF at longer task delays in medial regions, and decreased rCBF over delay conditions in lateral cortical areas. These results indicate that, during cholinergic potentiation, brain activity in prefrontal regions is not modulated by increases in WM task demands, and lends further support to the hypothesis that cholinergic modulation enhances visual processing, making the task easier to perform, and thus, compensate for the need to recruit prefrontal cortical regions as task demands increase. C1 [Furey, Maura L.; Rapoport, Stanley I.] NIH, Bethesda, MD 20892 USA. [Ricciardi, Emiliano; Pietrini, Pietro] Univ Pisa, I-56100 Pisa, Italy. [Schapiro, Mark B.] Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. [Ricciardi, Emiliano] Univ Studies & Doctoral Res, St Anna Sch, Pisa, Italy. RP Furey, ML (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. RI Furey, Maura/H-5273-2013; Ricciardi, Emiliano/E-6929-2011 OI Ricciardi, Emiliano/0000-0002-7178-9534 FU Intramural NIH HHS [Z01 AG000148-07] NR 41 TC 21 Z9 22 U1 1 U2 2 PU M I T PRESS PI CAMBRIDGE PA 238 MAIN STREET, STE 500, CAMBRIDGE, MA 02142-1046 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD JUL PY 2008 VL 20 IS 7 BP 1342 EP 1353 DI 10.1162/jocn.2008.20092 PG 12 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 323PX UT WOS:000257460700015 PM 18284346 ER PT J AU Bassim, CW Redman, RS DeNucci, DJ Becker, KL Nylen, ES AF Bassim, C. W. Redman, R. S. DeNucci, D. J. Becker, K. L. Nylen, E. S. TI Salivary procalcitonin and periodontitis in diabetes SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE saliva; procalcitonin; periodontitis; diabetes ID SYSTEMIC INFLAMMATION; CALCITONIN PRECURSORS; INSULIN-RESISTANCE; EXPRESSION; MELLITUS; DISEASE; SEPSIS; ADRENOMEDULLIN; RISK; MORTALITY AB Periodontitis and type 2 diabetes are co-morbid conditions, both characterized by infectious susceptibility. We investigated procalcitonin (ProCT) levels in the serum and saliva of persons with periodontitis and type 2 diabetes (n = 20), to determine if these levels are altered by periodontitis activity or by hyperglycemia. Persons with severe periodontitis showed higher levels of salivary-ProCT than did those with moderate periodontitis (241 +/- 71 vs. 77 +/- 516 pg/mL, p = 0.02) and higher levels than did healthy control individuals (118 +/- 26 pg/mL, p = 0.05). Salivary-ProCT levels were correlated with bleeding-on-probing (r = 0.45, p = 0.05), as well as with HgbA(1c) (r = 0.49, p = 0.03). Salivary levels of ProCT were higher than serum levels for the periodontitis/diabetes group ( 152 +/- 37 vs. 78 +/- 17 pg/mL, p = 0.02) and the control group (118 +/- 146 vs. 48 +/- 17 pg/mL, p = 0.01). Persons with periodontitis and type 2 diabetes have salivary-ProCT levels that reflect their degree of periodontitis activity and hyperglycemia. This study demonstrates, for the first time, the presence of procalcitonin (ProCT), an established serum marker of infection, in saliva. C1 [Bassim, C. W.; Redman, R. S.; DeNucci, D. J.; Becker, K. L.; Nylen, E. S.] Vet Affairs Med Ctr, Washington, DC 20422 USA. [Bassim, C. W.; DeNucci, D. J.] NIDCR, CRC, NIH, Bethesda, MD 20892 USA. [Becker, K. L.; Nylen, E. S.] George Washington Univ, Washington, DC USA. RP Bassim, CW (reprint author), Vet Affairs Med Ctr, 50 Irving St NW, Washington, DC 20422 USA. EM bassimc@mail.nih.gov NR 37 TC 14 Z9 17 U1 0 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 EI 1544-0591 J9 J DENT RES JI J. Dent. Res. PD JUL PY 2008 VL 87 IS 7 BP 630 EP 634 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 317KT UT WOS:000257019800005 PM 18573981 ER PT J AU Maggio, M Lauretani, F Basaria, S Ceda, GP Bandinelli, S Metter, EJ Bos, AJ Ruggiero, C Ceresini, G Paolisso, G Artoni, A Valenti, G Guralnik, JM Ferrucci, L AF Maggio, M. Lauretani, F. Basaria, S. Ceda, G. P. Bandinelli, S. Metter, E. J. Bos, A. J. Ruggiero, C. Ceresini, G. Paolisso, G. Artoni, A. Valenti, G. Guralnik, J. M. Ferrucci, L. TI Sex hormone binding globulin levels across the adult lifespan in women - The role of body mass index and fasting insulin SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION LA English DT Article DE Aging; BMI; insulin; SHBG; women ID CARDIOVASCULAR RISK-FACTORS; GROWTH-FACTOR-I; POSTMENOPAUSAL WOMEN; IGF-I; SHBG; TESTOSTERONE; AGE; PREMENOPAUSAL; TRANSITION; MENOPAUSE AB SHBG is a major carrier of androgens. In men, SHBG levels increase with age, while in women data are scant. There is evidence that body mass index (BMI) and fasting insulin influence SHBG concentration. Since low SHBG levels are predictors of insulin resistance and diabetes, understanding the relationship of SHBG with age, insulin, and BMI is important to gain insight into the role of SHBG as a cardiovascular risk factor in women. Differences in SHBG across adult life span and their relationship with insulin and BMI were evaluated in a representative cohort of 616 Italian women free of diabetes and not on hormone replacement therapy enrolled in the InCHIANTI Study. The relationship of SHBG with age, BMI, and fasting insulin levels was analyzed using linear regression and by loess smoother. Serum SHBG levels showed a U-shaped trajectory with age, declining from the 2(nd) to the 6(th) decade of life and increasing after the 6(th) decade (p<0.0001). Age-related trends for BMI and fasting insulin mirrored the trend observed for SHBG. After adjusting for fasting insulin, the relationship between log (SHBG) and age square was attenuated (beta coefficient from 0.00044 to 0.00039) and was further reduced after adjustment for BMI (from 0.00039 to 0.00028). SHBG levels show an age-related U-shaped trajectory. These changes mirror the age-related changes in BMI and fasting insulin, suggesting that BMI and insulin negatively influence SHBG concentration. (J. Endocrinol. Invest. 31: 597-601, 2008) (C) 2008, Editrice Kurtis C1 [Ferrucci, L.] Harbor Hosp, Clin Res Branch, NIA, NIH,NIA AS TRA Unit, Baltimore, MD 21225 USA. [Maggio, M.; Ceda, G. P.; Ceresini, G.; Artoni, A.; Valenti, G.] Univ Parma, Sect Geriatr, Dept Internal Med & Biomed Sci, Sch Endocrinol, I-43100 Parma, Italy. [Lauretani, F.] Tuscany Reg Hlth Agcy, Florence, Italy. [Basaria, S.] Johns Hopkins Univ, Sch Med, Dept Med, Div Endocrinol,Bayview Med Ctr, Baltimore, MD 21205 USA. [Bandinelli, S.] ASF, Geriatr Rehabil Unit, Florence, Italy. [Paolisso, G.] Univ Naples Federico 2, Dept Geriatr Med & Metab Dis 2, Naples, Italy. [Guralnik, J. M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Ferrucci, L (reprint author), Harbor Hosp, Clin Res Branch, NIA, NIH,NIA AS TRA Unit, 3001 S Hanover St, Baltimore, MD 21225 USA. EM ferruccilu@grc.nia.nih.gov RI Perez , Claudio Alejandro/F-8310-2010; Lauretani, Fulvio/K-5115-2016 OI Perez , Claudio Alejandro/0000-0001-9688-184X; Lauretani, Fulvio/0000-0002-5287-9972 FU National Institutes of Health (NIH); National Institute on Aging; Italian Ministry of Health [ICS110.1/RS97.71] FX The InCHIANTI study is supported in part by the Intramural Research Program of the National Institutes of Health (NIH), National Institute on Aging and as a "targeted project" (ICS110.1/RS97.71) by the Italian Ministry of Health. NR 24 TC 20 Z9 21 U1 0 U2 3 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 0391-4097 J9 J ENDOCRINOL INVEST JI J. Endocrinol. Invest. PD JUL PY 2008 VL 31 IS 7 BP 597 EP 601 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 358GQ UT WOS:000259905500004 PM 18787375 ER PT J AU Rogers, CG Blatt, AM Miles, GE Linehan, WM Pinto, PA AF Rogers, Craig G. Blatt, Adam M. Miles, George E. Linehan, W. Marston Pinto, Peter A. TI Concurrent robotic partial adrenalectomy and extra-adrenal pheochromocytoma resection in a pediatric patient with von Hippel-Lindau disease SO JOURNAL OF ENDOUROLOGY LA English DT Article ID EXPERIENCE AB Laparoscopic partial adrenalectomy is a surgical option for select patients with hereditary pheochromocytoma. We present a case of a pediatric patient with von Hippel-Lindau disease (VHL) and both an adrenal pheochromocytoma and an extra-adrenal pheochromocytoma, who underwent concurrent partial adrenalectomy and extra-adrenal pheochromocytoma resection utilizing robotic assistance. To the best of our knowledge, this is the first report of partial adrenalectomy with concurrent extra-adrenal pheochromocytoma resection. C1 [Rogers, Craig G.; Blatt, Adam M.; Linehan, W. Marston; Pinto, Peter A.] NCI, Urol Oncol Branch, Natl Inst Hlth, Ctr Canc Res, Bethesda, MD 20892 USA. [Miles, George E.] NCI, Pathol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Pinto, PA (reprint author), NCI, Urol Oncol Branch, Natl Inst Hlth, Ctr Canc Res, Bldg 10,Rm 1W-5940, Bethesda, MD 20892 USA. EM pintop@mail.nih.gov FU Intramural NIH HHS [Z01 SC006659-25] NR 7 TC 17 Z9 17 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD JUL PY 2008 VL 22 IS 7 BP 1501 EP 1503 DI 10.1089/end.2007.0314 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 336SN UT WOS:000258385000018 PM 18690816 ER PT J AU Mattson, MP AF Mattson, Mark P. TI Secretases, oxidative stress, and perturbed calcium homeostasis in AD and stroke SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-of-General-Physiologists CY SEP 03-07, 2008 CL Marine Biol Lab, Woods Hole, MA SP Soc Gen Physiol HO Marine Biol Lab C1 [Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 0 TC 1 Z9 1 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 2008 VL 132 IS 1 MA 30 BP 14A EP 14A PG 1 WC Physiology SC Physiology GA 354JC UT WOS:000259634900034 ER PT J AU Barth, H Robinet, E Liang, TJ Baumert, TF AF Barth, Heidi Robinet, Eric Liang, T. Jake Baumert, Thomas F. TI Mouse models for the study of HCV infection and virus-host interactions SO JOURNAL OF HEPATOLOGY LA English DT Review DE viral infection; transgenic mice; antivirals ID HEPATITIS-C-VIRUS; ACTIVATED-RECEPTOR-ALPHA; TRANSGENIC MICE; CORE PROTEIN; HEPATOCELLULAR-CARCINOMA; OXIDATIVE STRESS; CELL-CULTURE; STRUCTURAL PROTEINS; CRE/LOXP SYSTEM; HEPARAN-SULFATE AB Hepatitis C virus (HCV) is a major cause of chronic liver disease including steatosis, cirrhosis and hepatocellular carcinoma. The development of transgenic mice expressing HCV proteins and the successful repopulation of SCID/Alb-uPA mice with human hepatocytes provides an important tool for unraveling virus-host interactions in vivo. Several of these mouse models exhibit aspects of HCV-related liver disease. Thus, these in vivo models play an important role to further understand the pathogenesis of HCV infection and to evaluate the pre-clinical safety and efficacy of new antiviral compounds against HCV. This review summarizes the most important mouse models currently used to study HCV pathogenesis and infection. Finally, the perspective of these models for future HCV research as well as the design of novel small animal models is discussed. Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver. C1 [Barth, Heidi; Liang, T. Jake] NIDDK, NIH, Liver Dis Branch, Bethesda, MD 20892 USA. [Robinet, Eric; Baumert, Thomas F.] INSERM, U748, F-67000 Strasbourg, France. [Robinet, Eric; Baumert, Thomas F.] Univ Strasbourg 1, F-67000 Strasbourg, France. [Baumert, Thomas F.] CHU Strasbourg, Nouvel Hop Civil, Serv Hepatogastroenterol, F-67000 Strasbourg, France. RP Barth, H (reprint author), NIDDK, NIH, Liver Dis Branch, 10 Ctr Dr, Bethesda, MD 20892 USA. EM barthh@niddk.nih.gov; Thomas.Bau-mert@viro-ulp.u-strasbg.fr OI Eric, ROBINET/0000-0001-9765-805X FU Intramural NIH HHS [, NIH0013330684]; PHS HHS [NIH0013330684] NR 93 TC 40 Z9 40 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD JUL PY 2008 VL 49 IS 1 BP 134 EP 142 DI 10.1016/j.jhep.2008.03.012 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 323YK UT WOS:000257484300017 PM 18457898 ER PT J AU Kelley-Hedgepeth, A Peter, I Kip, KE Montefusco, MC Kogan, S Cox, D Ordovas, JM Levy, D Reis, SE Mendelsohn, ME Housman, D Huggins, GS AF Kelley-Hedgepeth, A. Peter, I. Kip, K. E. Montefusco, M. C. Kogan, S. Cox, D. Ordovas, J. M. Levy, D. Reis, S. E. Mendelsohn, M. E. Housman, D. Huggins, G. S. TI The protective effect of KCNMB1 E65K against hypertension is restricted to blood pressure treatment with beta-blockade SO JOURNAL OF HUMAN HYPERTENSION LA English DT Article ID DIASTOLIC HYPERTENSION; POTASSIUM CHANNEL; ASSOCIATION; SUBUNIT AB Genetic polymorphisms that influence smooth muscle cell contraction and relaxation may affect the response to anti-hypertensive therapy. Our finding of lower blood pressure in the setting of treatment for hypertension, particularly with beta-blockade, in Caucasian KCNMB1-E65K carriers in two community cohorts has implications for personalization of therapy in hypertension. C1 [Kelley-Hedgepeth, A.; Montefusco, M. C.; Kogan, S.; Cox, D.; Mendelsohn, M. E.; Huggins, G. S.] Tufts Med Ctr, Mol Cardiol Res Inst, MCRI Ctr Translat Genom, Boston, MA 02111 USA. [Peter, I.] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA USA. [Kip, K. E.] Univ S Florida, Tampa, FL USA. [Ordovas, J. M.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr, Boston, MA 02111 USA. [Levy, D.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Levy, D.] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Reis, S. E.] Univ Pittsburgh, Pittsburgh, PA USA. [Housman, D.] MIT, Cambridge, MA 02139 USA. RP Kelley-Hedgepeth, A (reprint author), Tufts Med Ctr, Mol Cardiol Res Inst, MCRI Ctr Translat Genom, Boston, MA 02111 USA. EM ghuggins@tufts-nemc.org RI Reis, Steven/J-3957-2014 FU NHLBI NIH HHS [HL069770, HL077378, N01-HC-25195, N01HC25195, P01 HL077378, P01 HL077378-05, T32 HL069770, T32 HL069770-05] NR 12 TC 18 Z9 19 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9240 J9 J HUM HYPERTENS JI J. Hum. Hypertens. PD JUL PY 2008 VL 22 IS 7 BP 512 EP 515 DI 10.1038/jhh.2008.23 PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 315LQ UT WOS:000256881900012 PM 18418400 ER PT J AU Pipeling, MR West, EE Osborne, CM Whitlock, AB Dropulic, LK Willett, MH Forman, M Valsamakis, A Orens, JB Moller, DR Lechtzin, N Migueles, SA Connors, M McDyer, JF AF Pipeling, Matthew R. West, Erin E. Osborne, Christine M. Whitlock, Amanda B. Dropulic, Lesia K. Willett, Matthew H. Forman, Michael Valsamakis, Alexandra Orens, Jonathan B. Moller, David R. Lechtzin, Noah Migueles, Stephen A. Connors, Mark McDyer, John F. TI Differential CMV-Specific CD8+ effector T cell responses in the lung allograft predominate over the blood during human primary infection the blood during human SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BRONCHIOLITIS-OBLITERANS-SYNDROME; TRANSPLANT RECIPIENTS; HUMAN CYTOMEGALOVIRUS; MURINE CYTOMEGALOVIRUS; BRONCHOALVEOLAR LAVAGE; ORGAN-TRANSPLANTATION; LYMPHOCYTE RESPONSE; IMMUNE-RESPONSES; VIRUS-INFECTIONS; CUTTING EDGE AB Acquisition of T cell responses during primary CMV infection in lung transplant recipients (LTRs) appear critical for host defense and allograft durability, with increased mortality in donor(+)/recipient(-) (D+R-) individuals. In 15 D+R- LTRs studied, acute primary CMV infection was characterized by viremia in the presence or absence of pneumonitis, with viral loads higher in the lung airways/allograft compared with the blood. A striking influx of CD8+ T cells into the lung airways/allograft was observed, with inversion of the CD4+:CD8+ T cell ratio. De novo CMV(-)specific CD8+ effector frequencies in response to pooled peptides of pp65 were strikingly higher in lung mononuclear cells compared with the PBMC and predominated over IE1-specific responses and CD4+ effector responses in both compartments. The frequencies of pp65-specific cytokine responses were significantly higher in lung mononuclear cells compared with PBMC and demonstrated marked contraction with long-term persistence of effector memory CD8+ T cells in the lung airways following primary infection. CMV-tetramer(+)CD(8+) T cells from PBMC were CD45RA(-) during viremia and transitioned to CD45RA(+) following resolution. In contrast, CMV-specific CD8+ effectors in the lung airways/allograft maintained a CD45RA(-) phenotype during transition from acute into chronic infection. Together, these data reveal differential CMV-specific CD8+ effector frequencies, immunodominance, and polyfunctional cytokine responses predominating in the lung airways/allograft compared with the blood during acute primary infection. Moreover, we show intercompartmental phenotypic differences in CMV-specific memory responses during the transition to chronic infection. C1 [Pipeling, Matthew R.; West, Erin E.; Whitlock, Amanda B.; Willett, Matthew H.; Orens, Jonathan B.; Moller, David R.; Lechtzin, Noah; McDyer, John F.] Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, Baltimore, MD 21224 USA. [Dropulic, Lesia K.] Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21224 USA. [Forman, Michael; Valsamakis, Alexandra] Johns Hopkins Univ, Sch Med, Dept Pathol & Med Microbiol, Baltimore, MD 21224 USA. [Osborne, Christine M.; Migueles, Stephen A.; Connors, Mark] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP McDyer, JF (reprint author), Johns Hopkins Univ, Dept Med, 5501 Bayview Circle,Room 4B51, Baltimore, MD 21224 USA. EM jmcdyer@jhmi.edu FU NHLBI NIH HHS [HL-068682, K08 HL068682-05, K08 HL068682]; NIAID NIH HHS [AI-072537, R21 AI072537-02, R21 AI072537] NR 56 TC 24 Z9 24 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 JUL 1 PY 2008 VL 181 IS 1 BP 546 EP 556 PG 11 WC Immunology SC Immunology GA 322WB UT WOS:000257404900061 PM 18566421 ER PT J AU Ueyama, T Kusakabe, T Karasawa, S Kawasaki, T Shimizu, A Son, J Leto, TL Miyawaki, A Saito, N AF Ueyama, Takehiko Kusakabe, Tomoko Karasawa, Satoshi Kawasaki, Takumi Shimizu, Aya Son, Jeonghyun Leto, Thomas L. Miyawaki, Atsushi Saito, Naoaki TI Sequential binding of cytosolic phox complex to phagosomes through regulated adaptor proteins: Evaluation using the novel monomeric kusabira-green system and live imaging of phagocytosis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; NEUTROPHIL NADPH OXIDASE; R-MEDIATED PHAGOCYTOSIS; SRC HOMOLOGY-3 DOMAINS; PX DOMAIN; SUPEROXIDE-PRODUCTION; LIVING CELLS; SH3 DOMAIN; FLUORESCENCE COMPLEMENTATION; MEMBRANE-BINDING AB We engineered a method for detecting intramolecular and intermolecular phox protein interactions in cells by fluorescence microscopy using fusion proteins of complementary fragments of a coral fluorescent reporter protein (monomeric Kusabira-Green). We confirmed the efficacy of the monomeric Kusabira-Green system by showing that the PX and PB1 domains of p40(phox) interact in intact cells, which we suggested maintains this protein in an inactive closed conformation. Using this system, we also explored intramolecular interactions within p47(phox) and showed that the PX domain interacts with the autoinhibited tandem Src homology 3 domains maintained in contact with the autoinhibitory region, along with residues 341-360. Furthermore, we demonstrated sequential interactions of p67(phox) , With phagosomes involving adaptor proteins, p47(phox) and p40(phox), during Fc gamma R-mediated phagocytosis. Although p67(phox) is not targeted to phagosomes by itself, p47(phox) functions as an adaptor for the ternary complex (p47(phox), -p67(phox)-p40(phox)) in early stages of phagocytosis before phagosome closure, while p40(phox) functions in later stages after phagosomal closure. Interestingly, a mutated "open" form of p40(phox), linked p47(phox), to closed phagosomes and prolonged p47(phox) and p67(phox) retention on phagosomes. These results indicate that binding of the ternary complex to phagosomes can be temporally regulated by switching between adaptor proteins that have PX domains with distinct lipid-binding specificities. C1 [Saito, Naoaki] Kobe Univ, Mol Pharmacol Lab, Biosignal Res Ctr, Nada Ku, Kobe, Hyogo 6578501, Japan. [Karasawa, Satoshi; Miyawaki, Atsushi] RIKEN, Brain Sci Inst, Lab Cell Funct & Dynam, Saitama, Japan. [Karasawa, Satoshi] Amalgaam, Tokyo, Japan. [Karasawa, Satoshi] Med & Biol Labs, Nagoya, Aichi, Japan. [Leto, Thomas L.] NIAID, Mol Def Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Saito, N (reprint author), Kobe Univ, Mol Pharmacol Lab, Biosignal Res Ctr, Nada Ku, 1-1 Rokkodai Cho, Kobe, Hyogo 6578501, Japan. EM naosaito@kobe-u.ac.jp RI Miyawaki, Atsushi/K-3569-2014 OI Miyawaki, Atsushi/0000-0002-2329-3235 NR 68 TC 35 Z9 36 U1 1 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 2008 VL 181 IS 1 BP 629 EP 640 PG 12 WC Immunology SC Immunology GA 322WB UT WOS:000257404900070 PM 18566430 ER PT J AU Haeryfar, SMM Hickman, HA Irvine, KR Tscharke, DC Bennink, JR Yewdell, JW AF Haeryfar, S. M. Mansour Hickman, Heather A. Irvine, Kari R. Tscharke, David C. Bennink, Jack R. Yewdell, Jonathan W. TI Terminal deoxynucleotidyl transferase establishes and broadens antiviral CD8(+) T cell immunodominance hierarchies SO JOURNAL OF IMMUNOLOGY LA English DT Article ID N-REGION DIVERSITY; REPERTOIRE DIVERSITY; INFLUENZA-VIRUS; RECEPTOR REPERTOIRE; MICE; RESPONSES; RECOGNITION; DETERMINANTS; DEFICIENCY; INFECTION AB The action of TdT on mouse TCR genes accounts for similar to 90% of T cell repertoire diversity. We report that in TdT(-/-) mice, total TCD8+ responses to influenza and vaccinia viruses are reduced by similar to 30% relative to wild-type mice. We find that TCD8+ responses to three subdominant influenza virus determinants are reduced to background values in TdT(-/-) mice while responses to three immunodominant determinants undergo a major reshuffling. A similar reshuffling occurs in TCD8+ responses to immunodominant vaccinia virus determinants, and is clearly based on broad differences in TCR family usage and CDR3 length between wild-type and TdT(-/-) mice. These findings demonstrate that TdT plays a critical role in the magnitude and breadth of anti-viral TCD8+ responses toward individual determinants and suggests that germline TCR repertoire bias toward the most dominant determinants is a major factor in establishing immunodominance hierarchies. C1 [Haeryfar, S. M. Mansour] Univ Western Ontario, Dept Microbiol & Immunol, London, ON N6A 5C1, Canada. [Haeryfar, S. M. Mansour; Hickman, Heather A.; Irvine, Kari R.; Tscharke, David C.; Bennink, Jack R.; Yewdell, Jonathan W.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. [Tscharke, David C.] Australian Natl Univ, Sch Biochem & Mol Biol, Canberra, ACT, Australia. RP Haeryfar, SMM (reprint author), Univ Western Ontario, Dept Microbiol & Immunol, London, ON N6A 5C1, Canada. EM mansour.haeryfar@schulich.uwo.ca; jyewdell@nih.gov RI yewdell, jyewdell@nih.gov/A-1702-2012; Tscharke, David/C-9133-2009 OI Tscharke, David/0000-0001-6825-9172 FU Intramural NIH HHS [Z01 AI000542-20, Z01 AI000814-11, Z01 AI001014-01] NR 38 TC 14 Z9 14 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 JUL 1 PY 2008 VL 181 IS 1 BP 649 EP 659 PG 11 WC Immunology SC Immunology GA 322WB UT WOS:000257404900072 PM 18566432 ER PT J AU Qian, L Wei, SJ Zhang, D Hu, XM Xu, ZL Wilson, B El-Benna, J Hong, JS Flood, PM AF Qian, Li Wei, Sung-Jen Zhang, Dan Hu, Xiaoming Xu, Zongli Wilson, Belinda El-Benna, Jamel Hong, Jau-Shyong Flood, Patrick M. TI Potent anti-inflammatory and neuroprotective effects of TGF-beta 1 are mediated through the inhibition of ERK and p47(phox)-Ser(345) phosphorylation and translocation in microglial SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LIPOPOLYSACCHARIDE-INDUCED NEUROTOXICITY; GROWTH-FACTOR BETA-1; NADPH OXIDASE; PARKINSONS-DISEASE; TGF-BETA; DOPAMINERGIC-NEURONS; CELL-DEATH; HIPPOCAMPAL-NEURONS; TETRAZOLIUM SALT; OXIDATIVE STRESS AB TGF-beta 1 is one of the most potent endogenous immune modulators of inflammation. The molecular mechanism of its anti-inflammatory effect on the activation of the transcription factor NF-kappa B has been well-studied; however, the potential effects of TGF-beta 1 on other proinflammatory signaling pathways is less clear. In this study, using the well-established LPS and the 1-methyl-4-phenylpyridinium-mediated models of Parkinson's disease, we demonstrate that TGF-beta 1 exerts significant neuroprotection in both models via its anti-inflammatory properties. The neuroprotective effects of TGF-beta 1 are mainly attributed to its ability to inhibit the production of reactive oxygen species from microglia during their activation or reactivation. Moreover, we demonstrate that TGF-beta 1 inhibited LPS-induced NADPH oxidase (PHOX) subunit p47(phox) translocation from the cytosol to the membrane in microglia within 10 min. Mechanistic studies show that TGF-beta 1 fails to protect dopaminergic neurons in cultures from PHOX knockout mice, and significantly reduced LPS-induced translocation of the PHOX cytosolic subunit p47(phox) to the cell membrane. In addition, LPS-induced ERK phosphorylation and subsequent Ser(345) phosphorylation on p47(phox) were significantly inhibited by TGF-beta 1 pretreatment. Taken together, our results show that TGF-beta 1 exerted potent anti-inflammatory and neuroprotective properties, either through the prevention of the direct activation of microglia by LPS, or indirectly through the inhibition of reactive microgliosis elicited by 1-methyl-4-phenylpyridinium. The molecular mechanisms of TGF-beta 1-mediated anti-inflammatory properties is through the inhibition of PHOX activity by preventing the ERK-dependent phosphorylation of Ser(345) on p47(phox) in microglia to reduce oxidase activities induced by LPS. C1 [Qian, Li; Flood, Patrick M.] Univ N Carolina, Comprehens Ctr Inflammatory Disorders, Chapel Hill, NC 27599 USA. [Qian, Li; Zhang, Dan; Hu, Xiaoming; Wilson, Belinda; Hong, Jau-Shyong] NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. [Xu, Zongli] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. [Wei, Sung-Jen] NIEHS, Natl Ctr Toxicogenom, Res Triangle Pk, NC 27709 USA. [El-Benna, Jamel] Univ Paris 07, Ctr Rech Biomed Bichat Beaujon, U773, INSERM, Paris, France. RP Flood, PM (reprint author), Univ N Carolina, Comprehens Ctr Inflammatory Disorders, Chapel Hill, NC 27599 USA. EM pat_flood@dentistry.unc.edu FU Intramural NIH HHS [Z99 ES999999, Z01 ES090082-11]; NIDCR NIH HHS [DE-13079, P60 DE013079, P60 DE013079-01] NR 46 TC 70 Z9 74 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 2008 VL 181 IS 1 BP 660 EP 668 PG 9 WC Immunology SC Immunology GA 322WB UT WOS:000257404900073 PM 18566433 ER PT J AU Breunis, WB Tarazona-Santos, E Chen, R Kiley, M Rosenberg, SA Chanock, SJ AF Breunis, Willemijn B. Tarazona-Santos, Eduardo Chen, Renee Kiley, Maureen Rosenberg, Steven A. Chanock, Stephen J. TI Influence of cytotoxic T lymphocyte-associated antigen 4 (CTLA4) common polymorphisms on outcome in treatment of melanoma patients with CTLA-4 blockade SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE CTLA4; single nucleotide polymorphism; CTLA-4 blockade; melanoma ID T-LYMPHOCYTE ANTIGEN-4; METASTATIC MELANOMA; GENE POLYMORPHISM; LINKAGE PHASE; AUTOIMMUNITY; ASSOCIATION; REGRESSION; ANTIBODY; CANCER; ALLELE AB Blockade of the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), a down-regulator of T-cell activation, can cause cancer regression in patients with metastatic melanoma. However, not all patients respond well to the therapy and some develop severe autoimmune reactions. We hypothesized that common genetic variation in the CTLA4 gene could contribute to response to CTLA-4 blockade and the occurrence of autoimmune reactions. We investigated 7 common single nucleotide polymorphisms, SNPs, (rs733618, rs4553808, rs11571317, rs5742909, rs231775, rs3087243, and rs7565213) in 152 white melanoma patients who received CTLA-4 blockade. Three SNPs were associated with response to therapy: proximal promoter SNPs, rs4553808 [P = 0.002; odds ratio (OR) 3.39; 95% confidence interval (CI), 1.62-7.10] and rs11571327 (P=0.02; OR 2.89; 95% CI, 1.23-6.83) and the nonsynonymous SNP rs231775 (Thr17Ala, P = 0.009; OR 0.39; 95% CI, 0.18-0.82). A haplotype analysis including the 7 SNPs suggested that the common haplotype, TACCGGG could be associated with no response (P = 0.02) whereas the haplotype TGCCAGG (P = 0.06; OR 4.13; 95% CI, 1.17-14.5) could be associated with response to the treatment. No significant association was observed for occurrence of severe autoimmune reactions (grade III/IV) either by single SNP or haplotype analyses. Our results suggest that genetic variation in CTLA4 could influence response to CTLA-4 blockade therapy in metastatic melanoma patients, but further studies are necessary to confirm the observed associations. C1 [Breunis, Willemijn B.; Tarazona-Santos, Eduardo; Chen, Renee; Kiley, Maureen; Chanock, Stephen J.] NCI, Sect Genom Variat, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Chen, Renee; Chanock, Stephen J.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. [Breunis, Willemijn B.] Univ Amsterdam, Acad Med Ctr, Emma Childrens Hosp, NL-1012 WX Amsterdam, Netherlands. [Tarazona-Santos, Eduardo] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Biol Geral, Minas Gerais, Brazil. RP Chanock, SJ (reprint author), NCI, Lab Translat Genom, Adv Technol Ctr, 8717 Grovemont Circle, Gaithersburg, MD 20892 USA. EM sc83a@nih.gov RI Chen, Robert/B-3899-2009 OI Chen, Robert/0000-0002-8371-8629 FU Intramural NIH HHS [Z99 CA999999] NR 17 TC 54 Z9 54 U1 0 U2 0 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 JUL-AUG PY 2008 VL 31 IS 6 BP 586 EP 590 PG 5 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 318HH UT WOS:000257081700008 PM 18528295 ER PT J AU Reif, DM McKinney, BA Motsinger, AA Chanock, SJ Edwards, KM Rock, MT Moore, JH Crowe, JE AF Reif, David M. McKinney, Brett A. Motsinger, Alison A. Chanock, Stephen J. Edwards, Kathryn M. Rock, Michael T. Moore, Jason H. Crowe, James E., Jr. TI Genetic basis for adverse events after smallpox vaccination SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID VACCINIA VIRUS; CARDIOVASCULAR-DISEASE; RHEUMATOID-ARTHRITIS; ASSOCIATION; EXPRESSION; RESPONSES; RECEPTOR; IFN; POLYMORPHISMS; IMMUNIZATION AB Identifying genetic factors associated with the development of adverse events might allow screening before vaccinia virus administration. Two independent clinical trials of the smallpox vaccine (Aventis Pasteur) were conducted in healthy, vaccinia virus-naive adult volunteers. Volunteers were assessed repeatedly for local and systemic adverse events (AEs) associated with the receipt of vaccine and underwent genotyping for 1442 single-nucleotide polymorphisms (SNPs). In the first study, 36 SNPs in 26 genes were associated with systemic AEs (P <= .05); these 26 genes were tested in the second study. In the final analysis, 3 SNPs were consistently associated with AEs in both studies. The presence of a nonsynonymous SNP in the methylenetetrahydrofolate reductase (MTHFR) gene was associated with the risk of AE in both trials (odds ratio [OR], 2.3 [95% confidence interval {CI}, 1.1-5.2] [P = .04] and OR, 4.1 [95% CI, 1.4-11.4] [P<. 01]). Two SNPs in the interferon regulatory factor-1 (IRF1) gene were associated with the risk of AE in both sample sets (OR, 3.2 [95% CI, 1.1-9.8] [P = .03] and OR, 3.0 [95% CI, 1.1-8.3] [P = .03]). Genetic polymorphisms in genes expressing an enzyme previously associated with adverse reactions to a variety of pharmacologic agents (MTHFR) and an immunological transcription factor (IRF1) were associated with AEs after smallpox vaccination in 2 independent study samples. C1 [Crowe, James E., Jr.] Vanderbilt Univ, Med Ctr, Program Vaccine Sci, Nashville, TN USA. [Edwards, Kathryn M.; Rock, Michael T.; Crowe, James E., Jr.] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN USA. [Crowe, James E., Jr.] Vanderbilt Univ, Med Ctr, Dept Microbiol & Immunol, Nashville, TN USA. [Reif, David M.] Dartmouth Med Sch, Comp Genet Lab, Lebanon, NH USA. [Moore, Jason H.] Dartmouth Med Sch, Dept Genet, Lebanon, NH USA. [Reif, David M.; Motsinger, Alison A.] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN USA. [McKinney, Brett A.] Univ Alabama Birmingham, Sch Med, Dept Genet, Birmingham, AL USA. [Chanock, Stephen J.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Crowe, JE (reprint author), T2220 Med Ctr N, 1161 21st Ave S, Nashville, TN 37232 USA. EM james.crowe@vanderbilt.edu RI Crowe, James/B-5549-2009; OI Crowe, James/0000-0002-0049-1079; Reif, David/0000-0001-7815-6767 FU NCRR NIH HHS [M01 RR-00095]; NIAID NIH HHS [K25 AI064625, K25-AI-64625, N01-AI-25462, N01AI25462, R01 AI059694, R01 AI059694-05, R01-AI-59694, R21 AI059365, R21-AI-59365]; NIGMS NIH HHS [R01 GM-62758, T32 GM062758] NR 39 TC 39 Z9 42 U1 1 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD JUL 1 PY 2008 VL 198 IS 1 BP 16 EP 22 DI 10.1086/588670 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 311XD UT WOS:000256632800006 PM 18454680 ER PT J AU Healey, LM Hahn, BK Rehm, CA Adelsberger, J Qin, J Follmann, DA Tavel, J Kovacs, JA Sereti, I Davey, RT AF Healey, Letha M. Hahn, Barbara K. Rehm, Catherine A. Adelsberger, Joseph Qin, Jing Follmann, Dean A. Tavel, Jorge Kovacs, Joseph A. Sereti, Irini Davey, Richard T., Jr. TI The effect of continuous versus pericycle antiretroviral therapy on IL-2 responsiveness SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID HIV-INFECTED PATIENTS; CONTROLLED-TRIAL; INTERLEUKIN-2; INTERRUPTION; EXPANSION; INDUCTION AB Background: Intermittent administration of interleukin-2 (IL-2) to human immunodeficiency virus (HIV)-infected patients on antiretroviral therapy (ART) is capable of inducing significant increases in CD4 T cell counts as a result of increased T cell survival and decreased cell turnover. However, its role in the setting of ART interruptions (STI) is less well characterized. We sought to compare the effect of continuous (C) versus intermittent (P) ART on CD4 responses in patients undergoing IL-2 therapy. Methods: CD4 cell responses were compared in 25 patients who underwent IL-2 therapy during periods of continuous ART (n = 90 cycles) as well as during STI (n = 45 cycles). During STI, patients resumed ART for only 10 days surrounding each IL-2 cycle. Results: C cycles resulted in a significantly greater CD4 gain than P cycles (Delta 156 cells/mu L, 95% CI = 68-243). In multivariate analyses, baseline CD4/CD25 expression and treatment arm remained strong predictors of CD4 gain while CD8/CD38(+), CD8/DR+, and CD4 Ki67(+) phenotype were not predictive. Conclusions: Continuous ART was associated with a statistically significantly greater CD4 cell response to IL-2 therapy than was intermittent ART. These observations may have important implications for the appropriate integration of IL-2 therapy into STI strategies. C1 [Davey, Richard T., Jr.] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA. [Healey, Letha M.; Hahn, Barbara K.; Kovacs, Joseph A.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD USA. [Adelsberger, Joseph] SAIC Inc, Frederick, MD USA. RP Davey, RT (reprint author), NIAID, Div Clin Res, NIH, 10 Ctr Dr,Room 4-1479, Bethesda, MD 20892 USA. EM rdavey@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000865-08] NR 16 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD JUL PY 2008 VL 28 IS 7 BP 455 EP 461 DI 10.1089/jir.2007.0120 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 341DN UT WOS:000258694500005 PM 18597618 ER PT J AU Zhu, BM Ishida, Y Robinson, GW Pacher-Zavisin, M Yoshimura, A Murphy, PM Hennighausen, L AF Zhu, Bing-Mei Ishida, Yuko Robinson, Gertraud W. Pacher-Zavisin, Margit Yoshimura, Akihiko Murphy, Philip M. Hennighausen, Lothar TI SOCS3 negatively regulates the gp130-STAT3 pathway in mouse skin wound healing SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID GROWTH-FACTOR-ALPHA; KERATINOCYTE MIGRATION; TRANSCRIPTION FACTORS; ESSENTIAL INVOLVEMENT; FACTOR RECEPTOR; MAMMARY-GLAND; MICE; STAT3; GENE; EXPRESSION AB Proliferation and differentiation of keratinocytes during wound healing are regulated by cytokines and chemokines, which are secreted by resident and inflammatory cells and activate the transcription factor signal transducer and activator of transcription (STAT)3. However, it is not clear to what extent STAT3 in keratinocytes is activated by gp130-containing receptors. We addressed this question genetically by deleting the suppressor of cytokine signaling (SOCS) 3, a negative regulator of gp130-mediated STAT3 activation. Socs3 alleles flanked by loxP sites were deleted in mice with either an MMTV-Cre or K5-Cre transgene. While both transgenes are active in keratinocytes, the MMTV-Cre deletes floxed genes also in immune cells. Deletion of Socs3 using the MMTV-Cre transgene resulted in aberrant STAT3 activation, impaired wound healing, prolonged secretion of chemokines, a hyperproliferative epidermis, and neutrophil infiltration into wounds. Simultaneous deletion of the Socs3 and gp130 genes restored normal wound healing. Moreover, deletion of Socs3 only in keratinocytes caused impaired wound healing. These results demonstrate that wound healing is controlled in keratinocytes by the gp130-SOCS3-STAT3 pathway and an imbalance of this pathway results in delayed wound healing. C1 [Zhu, Bing-Mei; Robinson, Gertraud W.; Pacher-Zavisin, Margit; Hennighausen, Lothar] NIDDK, Lab Genet & Physiol, Natl Inst Hlth, Bethesda, MD 20892 USA. [Ishida, Yuko; Murphy, Philip M.] NIAID, Lab Mol Immunol, Mol Signalling Sect, Natl Inst Hlth, Bethesda, MD 20892 USA. [Yoshimura, Akihiko] Kyushu Univ, Med Inst Bioregulat, Fukuoka 812, Japan. RP Hennighausen, L (reprint author), NIDDK, Lab Genet & Physiol, Natl Inst Hlth, Bldg 8,Room 101,8 Ctr Dr, Bethesda, MD 20892 USA. EM lotharh@mail.nih.gov RI Robinson, Gertraud/I-2136-2012; Yoshimura, Akihiko/K-5515-2013 FU Intramural NIH HHS NR 32 TC 25 Z9 25 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2008 VL 128 IS 7 BP 1821 EP 1829 DI 10.1038/sj.jid.5701224 PG 9 WC Dermatology SC Dermatology GA 312HM UT WOS:000256659900030 PM 18185532 ER PT J AU Carregaro, V Valenzuela, JG Cunha, TM Verri, WA Grespan, R Matsumura, G Ribeiro, JMC Elnaiem, DE Silva, JS Cunha, FQ AF Carregaro, Vanessa Valenzuela, Jesus G. Cunha, Thiago M. Verri, Waldiceu A., Jr. Grespan, Renata Matsumura, Graziela Ribeiro, Jose M. C. Elnaiem, Dia-Eldin Silva, Joao S. Cunha, Fernando Q. TI Phlebotomine salivas inhibit immune inflammation-induced neutrophil migration via an autocrine DC-derived PGE(2)/IL-10 sequential pathway SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE antigen presentation; anti-inflammatory mediators; inflammatory diseases; cytokines; insect saliva; sand fly ID NECROSIS-FACTOR-ALPHA; FLY LUTZOMYIA-LONGIPALPIS; COLONY-STIMULATING FACTOR; DENDRITIC CELL-FUNCTION; NITRIC-OXIDE PRODUCTION; NAIVE T-CELLS; LEISHMANIA-MAJOR; CUTANEOUS LEISHMANIASIS; ARTHROPOD SALIVA; GLAND LYSATE AB In the present study, we investigated whether saliva from Phlebotomus papatasi and Phlebotomus duboscqi inhibited antigen-induced neutrophil migration and the mechanisms involved in these effects. The pretreatment of immunized mice with salivary gland extracts (SGE) of both phlebotomines inhibited OVA challenge-induced neutrophil migration and release of the neutrophil chemotactic mediators, MIP-1 alpha, TNF-alpha, and leukotriene B-4 (LTB4). Furthermore, SGE treatment enhanced the production of anti-inflammatory mediators, IL-10 and PGE(2). SGE treatments failed to inhibit neutrophil migration and MIP-1 alpha and LTB4 production in IL-10(-/-) mice, also failing in mice treated with nonselective (indomethacin) or selective (rofecoxibe) cyclooxygenase (COX) inhibitors. COX inhibition resulted in diminished SGE-induced IL-10 production, and PGE(2) release triggered by SGE remained increased in IL-10(-/-) mice, suggesting that prostanoids are acting through an IL-10-dependent mechanism. SGE treatments in vivo reduced the OVA-induced lymphoproliferation of spleen-derived cells. Further, the in vitro incubation of bone marrow-derived dendritic cells (DC) with SGE inhibited the proliferation of CD4(+) T cells from OVA-immunized mice, which was reversed by indomethacin and anti-IL-10 antibody treatments. Supporting these results, SGE induced the production of PGE(2) and IL-10 by DC, which were blocked by COX inhibition. These effects were associated with the reduction of DC-membrane expression of MHC-II and CD86 by SGE treatment. Altogether, the results showed that Phlebotomine saliva inhibits immune inflammation-induced neutrophil migration by an autocrine DC sequential production of PGE(2)/IL-10, suggesting that the saliva constituents might be promising therapeutic molecules to target immune inflammatory diseases. C1 [Cunha, Thiago M.; Verri, Waldiceu A., Jr.; Grespan, Renata; Matsumura, Graziela; Cunha, Fernando Q.] Univ Sao Paulo, Dept Pharmacol, Sch Med Ribeiro Preto, BR-14049900 Ribeirao Preto, SP, Brazil. [Carregaro, Vanessa; Silva, Joao S.] Univ Sao Paulo, Dept Biochem & Immunol, Sch Med Ribeiro Preto, BR-14049900 Ribeirao Preto, SP, Brazil. [Valenzuela, Jesus G.; Elnaiem, Dia-Eldin] Vector Mol Biol Unit, Bethesda, MD USA. [Ribeiro, Jose M. C.] NIAID, Vector Biol Sect, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RP Cunha, FQ (reprint author), Univ Sao Paulo, Dept Pharmacol, Sch Med Ribeiro Preto, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP, Brazil. EM fdqcunha@fmrp.usp.br RI Cunha, Thiago/B-7729-2012; Carregaro, Vanessa/D-2913-2012; Verri, Waldiceu/I-1330-2013; Silva, Joao/A-4484-2008; Cunha, Fernando/M-3090-2014; OI Cunha, Thiago/0000-0003-1084-0065; Ribeiro, Jose/0000-0002-9107-0818; Verri, Waldiceu/0000-0003-2756-9283; Cunha, Fernando Queiroz/0000-0003-4755-1670 FU Intramural NIH HHS NR 79 TC 21 Z9 22 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JUL 1 PY 2008 VL 84 IS 1 BP 104 EP 114 DI 10.1189/jlb.1107797 PG 11 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 331NZ UT WOS:000258020200009 PM 18390928 ER PT J AU Boesze-Battaglia, K Damek-Poprawa, M Mitchell, DC Greeley, L Brush, RS Anderson, RE Richards, MJ Fliesler, SJ AF Boesze-Battaglia, Kathleen Damek-Poprawa, Monika Mitchell, Drake C. Greeley, Laura Brush, Richard S. Anderson, Robert E. Richards, Michael J. Fliesler, Steven J. TI Alteration of retinal rod outer segment membrane fluidity in a rat model of Smith-Lemli-Opitz syndrome SO JOURNAL OF LIPID RESEARCH LA English DT Article ID FLUORESCENT-PROBES; CHOLESTEROL-SYNTHESIS; STEROL-METABOLISM; VERTEBRATE RETINA; MOLECULAR ORDER; INBORN-ERRORS; PHOSPHOLIPIDS; BILAYERS; ACID; DEPOLARIZATION AB Smith-Lemli-Opitz syndrome (SLOS) is caused by an inherited defect in the last step in cholesterol (Chol) biosynthesis, leading to abnormal accumulation of 7-dehydrocholesterol and decreased Chol levels. Progressive retinal degeneration occurs in an animal model of SLOS, induced by treating rats with AY9944, a selective inhibitor of the enzyme affected in SLOS. Here we evaluated alterations in the biochemical and physical properties of retinal rod outer segment (ROS) membranes in this animal model. At 1 month of AY9944 treatment, there were modest alterations in fatty acid composition, but no significant differences in cis-parinaric acid (cPA) spectroscopic parameters in ROS membranes from treated versus control rats. However, at 3 months, ROS docosahexaenoic acid (DHA) content was dramatically reduced, and cPA fluorescence anisotropy values were decreased, relative to controls. Also, 1,6-diphenyl-1,3,5-hexatriene exhibited decreased rotational motion and increased orientational order in ROS membranes from 3 month-old AY9944-treated rats, relative to controls. No significant changes in protein: lipid ratios were observed; however, rhodopsin regenerability was compromised by 3 months of treatment. These findings are consistent with reduced ROS membrane fluidity in the SLOS rat model, relative to controls, primarily due to the dramatic reduction in membrane DHA levels, rather than altered sterol composition. C1 [Richards, Michael J.; Fliesler, Steven J.] St Louis Univ, Sch Med, Dept Ophthalmol, Inst Eye, St Louis, MO 63104 USA. [Fliesler, Steven J.] St Louis Univ, Sch Med, Dept Pharmacol & Physiol Sci, St Louis, MO 63104 USA. [Boesze-Battaglia, Kathleen; Damek-Poprawa, Monika] Univ Penn, Sch Dent Med, Dept Biochem, Philadelphia, PA 19104 USA. [Mitchell, Drake C.; Greeley, Laura] NIAAA, Lab Membrane Biochem & Biophys, Natl Inst Hlth, Bethesda, MD 20892 USA. [Brush, Richard S.; Anderson, Robert E.] Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK 73104 USA. [Anderson, Robert E.] Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, Oklahoma City, OK 73104 USA. [Brush, Richard S.; Anderson, Robert E.] Dean McGee Eye Inst, Oklahoma City, OK 73104 USA. RP Fliesler, SJ (reprint author), St Louis Univ, Sch Med, Dept Ophthalmol, Inst Eye, St Louis, MO 63104 USA. EM fliesler@slu.edu FU NCRR NIH HHS [P20 RR017703, S10 RR026365, S10 RR026365-01, RR-17703]; NEI NIH HHS [R29 EY010420, R01 EY010420-10A2, R01 EY010420-11, R01 EY010420-13A2, R21 EY018705-01A1, R01 EY010420-14, R01 EY010420-08, R29 EY010420-03, EY-00871, EY-10420, EY-12190, P30 EY012190, R01 EY000871, R01 EY007361-16, R01 EY010420, R01 EY010420-07, R01 EY010420-16, EY-007361, R01 EY007361, EY-04149, R01 EY004149, R01 EY010420-06, R01 EY010420-09, R01 EY010420-12, R01 EY010420-15, R21 EY018705, R21 EY018705-02]; NIDCR NIH HHS [R01 DE022465] NR 42 TC 17 Z9 17 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD JUL PY 2008 VL 49 IS 7 BP 1488 EP 1499 DI 10.1194/jlr.M800031-JLR200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 313DC UT WOS:000256720300013 PM 18344409 ER PT J AU Massad, LS Evans, CT D'Souza, G Darragh, T Minkoff, H Henry, D Goparaju, L Muderspach, LI Watts, DH AF Massad, L. Stewart Evans, Charlesnika T. D'Souza, Gypsyamber Darragh, Teresa Minkoff, Howard Henry, Donna Goparaju, Lakshm Muderspach, Laila I. Watts, D. Heather TI High-Grade Cervical Disease in Adolescents With HIV SO JOURNAL OF LOWER GENITAL TRACT DISEASE LA English DT Article DE HPV; adolescents; cervical cancer prevention; Pap test; HIV in women ID WOMENS INTERAGENCY HIV; SQUAMOUS INTRAEPITHELIAL LESION; PAPILLOMAVIRUS INFECTION; YOUNG-WOMEN; CANCER; ABNORMALITIES; PREVALENCE; REGRESSION AB Objective. To estimate the risk of high-grade squamous intraepithelial lesions (HSIL) in adolescents with HIV. Materials and Methods. Review of cervical cytology and biopsy results from women aged 20 years and younger obtained within 3 years of enrollment in a prospective multicenter study. Results. At enrollment, none of 132 adolescent participants (45 HIV seropositive and 87 seronegative) had HSIL or cervical intraepithelial neoplasia grade 2 or 3 (CIN 2,3). Eight (7%) of 123 women with follow-up developed highgrade disease after a median of 2.6 years of observation. The incidence of HSIL/CIN 2,3 was 2.7/100 person-years (4.8/100 person-years in HIV seropositive and 1.6/100 person-years in HIV seronegative women; relative risk = 3.1; 95% CI = 0.76-12.74; p = .13). No cancers were found in adolescents during the study. Conclusions. The low incidence of HSIL or CIN 23 in adolescents suggests that optimal management is careful observation rather than preventive treatment of low-grade abnormalities. C1 [Massad, L. Stewart] Washington Univ, Sch Med, Div Gynecol & Oncol, St Louis, MO 63110 USA. [Evans, Charlesnika T.] Univ Illinois, Sch Publ Hlth, Chicago, IL USA. [D'Souza, Gypsyamber] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Darragh, Teresa] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Minkoff, Howard] Malmonides Med Ctr, Brooklyn, NY USA. [Henry, Donna] Montefiore Med Ctr, Bronx, NY 10467 USA. [Goparaju, Lakshm] Georgetown Univ, Washington, DC USA. [Muderspach, Laila I.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Watts, D. Heather] NICHHD, Bethesda, MD 20892 USA. RP Massad, LS (reprint author), Washington Univ, Sch Med, Div Gynecol & Oncol, 4911 Barnes Jewish Hosp Plaza, St Louis, MO 63110 USA. EM massadl@wudosis.wustl.edu FU NCI NIH HHS [P30 CA006973] NR 16 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1089-2591 J9 J LOW GENIT TRACT DI JI J. Low. Genit. Tract. Dis. PD JUL PY 2008 VL 12 IS 3 BP 199 EP 203 DI 10.1097/LGT.0b013e318160b9a5 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 382XA UT WOS:000261637500004 PM 18596461 ER PT J AU Dao, A Adamou, A Yaro, AS Maiga, HM Kassogue, Y Traore, SF Lehmann, T AF Dao, Adama Adamou, Abdoulaye Yaro, Alpha Seydou Maiga, Hamidou Moussa Kassogue, Yaya Traore, Sekou Fantamady Lehmann, Tovi TI Assessment of alternative mating strategies in Anopheles gambiae: Does mating occur indoors? SO JOURNAL OF MEDICAL ENTOMOLOGY LA English DT Article DE Anopheles gambiae; alternative mating strategies; molecular forms ID MOLECULAR M-FORM; SWARMING BEHAVIOR; GENETIC DIFFERENTIATION; INCIPIENT SPECIATION; FREEBORNI DIPTERA; DNA ANALYSIS; WEST-AFRICA; SAO-TOME; CULICIDAE; S.S. AB Mating in Anopheles gambiae has been observed only in outdoor swarms. Here we evaluate whether mating also occurs indoors. Mark-release-recapture of virgin males and females in natural houses showed that mating occurred over a single day even when mosquitoes can leave the house through exit traps and without adaptation to laboratory conditions. In these experiments, insemination rate in the M molecular form of An. gambiae (and An. arabiensis) was higher than that of the S form (15 versus 6%). Under these conditions, smaller females of the M form mated more frequently than larger females of that form. Sampling mosquitoes throughout the day showed that both sexes enter houses around sunrise and leave around sunset, staying indoors together from dawn to dusk. In an area dominated by the M form, the daily rate of insemination in samples from exit traps was approximate to 5% higher than in those from entry traps, implying that mating occurred indoors. Importantly, frequency of cross mating between the molecular forms was as high as that between members of the same form, indicating that, indoors, assortative mating breaks down. Altogether, these results suggest that indoor mating is an alternative mating strategy of the M molecular form of An. gambiae. Because naturally occurring mating couples have not yet been observed indoors, this conclusion awaits validation. C1 [Dao, Adama; Adamou, Abdoulaye; Yaro, Alpha Seydou; Kassogue, Yaya; Traore, Sekou Fantamady] Malaria Res & Training Ctr, Bamako, Mali. [Maiga, Hamidou Moussa] Univ Bamako, Fac Sci & Tech, Bamako, Mali. RP Lehmann, T (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM tlehmann@niaid.nih.gov FU Intramural NIH HHS [Z99 AI999999, ZIA AI001196-01, ZIA AI001196-02] NR 40 TC 24 Z9 24 U1 3 U2 4 PU ENTOMOLOGICAL SOC AMER PI LANHAM PA 10001 DEREKWOOD LANE, STE 100, LANHAM, MD 20706-4876 USA SN 0022-2585 J9 J MED ENTOMOL JI J. Med. Entomol. PD JUL PY 2008 VL 45 IS 4 BP 643 EP 652 DI 10.1603/0022-2585(2008)45[643:AOAMSI]2.0.CO;2 PG 10 WC Entomology; Veterinary Sciences SC Entomology; Veterinary Sciences GA 328AB UT WOS:000257768500008 PM 18714863 ER PT J AU Elnaiem, DEA Kelley, K Wright, S Laffey, R Yoshimura, G Reed, M Goodman, G Thiemann, T Reimer, L Reisen, WK Brown, D AF Elnaiem, Dia-Eldin A. Kelley, Kara Wright, Stan Laffey, Rhonda Yoshimura, Glenn Reed, Marcia Goodman, Gary Thiemann, Tara Reimer, Lisa Reisen, William K. Brown, David TI Impact of aerial spraying of pyrethrin insecticide on Culex pipiens and Culex tarsalis (Diptera : Culicidae) abundance and West Nile virus infection rates in an urban/suburban area of Sacramento County, California SO JOURNAL OF MEDICAL ENTOMOLOGY LA English DT Article DE West Nile virus; vector-borne disease; mosquitoes; California; control ID MOSQUITO-CONTROL; TRANSMISSION AB In response to an epidemic amplification of West Nile virus (family Flavivftldae, genus Flavivirm, WNV), the Sacramento and Yolo Mosquito and Vector Control District (SYMVCD) sprayed ultralow-volume (LTLV) formulations of pyrethrin insecticide (Evergreen EC 60-6: 6% pyrethrin insecticide, 60% piperonyl butoxide; MGK, Minneapolis, MN, applied as 0.003 kg/ ha [0.0025 lb /acre]) over 218 km(2) in north Sacramento and 243.5 km(2) in south Sacramento on three consecutive evenings in August 2005. We evaluated the impact of this intervention in north Sacramento on the abundance and WNV infection rates of Culex pipiens L. and Culex tarsalis Coquillett. Mortality rates of caged Cx. tarsalis sentinels ranged from 0% under dense canopy to 100% in open fields. A comparison of weekly geometric mean mosquito abundance in CO(2)-baited traps in sprayed and unsprayed areas before and after treatment indicated a 75.0 and 48.7% reduction in the abundance of Cx. pipiens and Cx. tarsalis, respectively. This reduction was statistically significant for Cx. pipiens, the primary vector of WNV, with highest abundance in this urban area, but not for Cx. tarsalis, which is more associated with rural areas. The infection rates of WNV in Cx. pipiens and Cx. tarsalis collected from the spray zone were 8.2 and 4.3 per 1,000 female mosquitoes in the 2 wk before and the 2 wk after applications of insecticide, respectively. In comparison, WNV infection rates in Cx. pipiens and Cx. tarsalis collected at same time interval in the unsprayed zone were 2.0 and 8.7 per 1,000, respectively. Based on the reduction in vector abundance and its effects on number of infective bites received by human population, we concluded that the aerial application of pyrethrin insecticide reduced the transmission intensity of WNV and decreased the risk of human infection. C1 [Elnaiem, Dia-Eldin A.; Kelley, Kara; Wright, Stan; Laffey, Rhonda; Yoshimura, Glenn; Reed, Marcia; Goodman, Gary; Brown, David] Sacramento Yolo Cty Mosquito & Vector Control Dis, Elk Grove, CA 95624 USA. [Thiemann, Tara; Reisen, William K.] Univ Calif Davis, Sch Vet Med, Ctr Vectorborne Dis, Davis, CA 95616 USA. [Reimer, Lisa] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. RP Elnaiem, DEA (reprint author), NIAID, LMVR, NIH, Twinbrook 3,Room 2E32,12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM elnaiemd@niaid.nih.gov FU FIC NIH HHS [K01 TW008778] NR 27 TC 23 Z9 23 U1 1 U2 7 PU ENTOMOLOGICAL SOC AMER PI LANHAM PA 10001 DEREKWOOD LANE, STE 100, LANHAM, MD 20706-4876 USA SN 0022-2585 J9 J MED ENTOMOL JI J. Med. Entomol. PD JUL PY 2008 VL 45 IS 4 BP 751 EP 757 DI 10.1603/0022-2585(2008)45[751:IOASOP]2.0.CO;2 PG 7 WC Entomology; Veterinary Sciences SC Entomology; Veterinary Sciences GA 328AB UT WOS:000257768500024 PM 18714879 ER PT J AU Hurst, SA Reiter-Theil, S Slowther, AM Pegoraro, R Forde, R Danis, M AF Hurst, S. A. Reiter-Theil, S. Slowther, A-M Pegoraro, R. Forde, R. Danis, M. TI Should ethics consultants help clinicians face scarcity in their practice? SO JOURNAL OF MEDICAL ETHICS LA English DT Article ID HEALTH-CARE COSTS; PHYSICIANS; BEDSIDE; EXPERIENCES; SERVICE; DOCTORS AB In an international survey of rationing we have found that European physicians encounter scarcity-related ethical difficulties, and are dissatified with the resolution of many of these cases. Here we further examine survey results to explore whether ethics support services would be potentially useful in addressing scarcity related ethical dilemmas. Results indicate that while the type of help offered by ethics support services was considered helpful by physicians, they rarely referred difficulties regarding scarcity to ethics consultation. We propose that ethics consultants could assist physicians by making the process less difficult, and by contributing to decisions being more ethically justifiable. Expertise in bringing considerations of justice to bear on real cases could also be useful in recognising an unjust limit, as opposed to a merely frustrating limit. Though these situations are unlikely to be among the most frequently referred to ethics support services, ethics consultants should be prepared to address them. C1 [Danis, M.] NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. [Hurst, S. A.] Univ Geneva, Sch Med, Inst Biomed Eth, CH-1211 Geneva, Switzerland. [Reiter-Theil, S.] Univ Basel, Inst Appl Eth, Basel, Switzerland. [Slowther, A-M] Univ Oxford, Ethox Ctr, Headington, England. [Pegoraro, R.] Fdn Lanza, Padua, Italy. [Forde, R.] Norwegian Med Associat, Inst Res, Oslo, Norway. [Forde, R.] Univ Oslo, Oslo, Norway. RP Danis, M (reprint author), NIH, Dept Clin Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM mdanis@cc.nih.gov RI Hurst, Samia/A-9661-2008 OI Hurst, Samia/0000-0002-1980-5226 NR 50 TC 14 Z9 14 U1 1 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 J9 J MED ETHICS JI J. Med. Ethics PD JUL 1 PY 2008 VL 34 IS 4 BP 241 EP 246 DI 10.1136/jme.2006.019828 PG 6 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 280YD UT WOS:000254461800005 PM 18375673 ER PT J AU Palmer, RJ AF Palmer, Robert J., Jr. TI Pictures of microbiology - The Biofilm Imaging Facility under Dr. David C. White SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE confocal microscopy; biofilms; luciferase; green fluorescent protein ID TRANSFORM INFRARED-SPECTROSCOPY; MICROSCOPY; EXPRESSION; FLOWCELL; CELLS AB This contribution honoring David C. White (DC) summarizes the five years I interacted with him on a daily basis in his laboratory. Over this time we worked on many different projects all tied together by the unifying principle now recognized as central to bacterial life in nature: biofilms. My goal is to convey some of the excitement and joy of working with DC and, from my perspective, that means telling how the Biofilm Imaging Facility at the Center for Environmental Biotechnology (CEB) came into existence and describing some of the projects on which DC and I worked. Published by Elsevier B.V. C1 Natl Inst Dent & Craniofacial Res, Oral Biofilm Commun Unit, Oral Infect & Immun Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Palmer, RJ (reprint author), Natl Inst Dent & Craniofacial Res, Oral Biofilm Commun Unit, Oral Infect & Immun Branch, Natl Inst Hlth, Bldg 30,Room 310 30 Convent Dr, Bethesda, MD 20892 USA. EM jpalmer@mail.nih.gov FU Intramural NIH HHS NR 15 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7012 J9 J MICROBIOL METH JI J. Microbiol. Methods PD JUL PY 2008 VL 74 IS 1 BP 5 EP 9 DI 10.1016/j.mimet.2007.07.003 PG 5 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 317RM UT WOS:000257037300002 PM 17698230 ER PT J AU Jeitner, TM Matson, WR Folk, JE Blass, JP Cooper, AJL AF Jeitner, Thomas M. Matson, Wayne R. Folk, John E. Blass, John P. Cooper, Arthur J. L. TI Increased levels of gamma-glutamylamines in Huntington disease CSF SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE gamma-glutamylputrescine; gamma-lutamylspermidine; gamma-glutamyle-epsilon-lysine; bis-gamma-glutamylputrescine; CSF; Huntington disease ID TRANSGLUTAMINASE INHIBITOR CYSTAMINE; TISSUE TRANSGLUTAMINASE; CROSS-LINKING; NEURODEGENERATIVE DISEASES; MOUSE MODEL; CEREBROSPINAL-FLUID; ALZHEIMERS-DISEASE; CELIAC-DISEASE; HUMAN BRAIN; POLYAMINES AB Transglutaminases (TGases) catalyze several reactions with protein substrates, including formation of gamma-glutamyl-epsilon-lysine cross-links and gamma-glutamylpolyamine residues. The resulting gamma-glutamylamines are excised intact during proteolysis. TGase activity is altered in several diseases, highlighting the importance of in situ enzymatic determinations. Previous work showed that TGase activity (as measured by an in vitro assay) and free gamma-glutamyl-epsilon-lysine levels are elevated in Huntington disease (HD) and that gamma-glutamyl-epsilon-lysine is increased in HD CSF. Although free gamma-glutamyl-epsilon-lysine was used in these studies as an index of in situ TGase activity, gamma-glutamylpolyamines may also be diagnostic. We have devised methods for the simultaneous determination of four gamma-glutamylamines in CSF: gamma-glutamyl-epsilon-lysine, gamma-glutamylspermidine, gamma-glutamylputrescine, and bis-gamma-glutamylputrescine and showed that all are present in normal human CSF at concentrations of similar to 150, 670, 40, and 240 nM, respectively. The high gamma-glutamylspermidine/gamma-glutamylputrescine and gamma-glutamylspermidine/bis-gamma-glutamylputrescine ratios presumably reflect in part the large spermidine to putrescine mole ratio in human brain. We also showed that all four gamma-glutamylamines are elevated in HD CSF. Our findings support the hypotheses that (i) gamma-glutamylpolyamines are reflective of TGase activity in human brain, (ii) polyamination is an important post-translational modification of brain proteins, and (iii) TGase-catalyzed modification of proteins is increased in HD brain. C1 [Jeitner, Thomas M.] Red Anvil LLC, Milwaukee, WI USA. [Matson, Wayne R.] Bedford Vet Adm Med Ctr, Dept Syst Biochem, Bedford, MA USA. [Folk, John E.] Natl Inst Drug Abuse, Chem Biol Res Branch, Bethesda, MD USA. [Blass, John P.; Cooper, Arthur J. L.] Burke Med Res Inst, White Plains, NY USA. [Blass, John P.; Cooper, Arthur J. L.] Cornell Univ, Weill Med Coll, Dept Neurol, New York, NY 10021 USA. [Blass, John P.] Cornell Univ, Weill Med Coll, Dept Med, New York, NY 10021 USA. [Cooper, Arthur J. L.] Cornell Univ, Weill Med Coll, Dept Biochem, New York, NY 10021 USA. RP Cooper, AJL (reprint author), New York Med Coll, Dept Biochem & Mol Biol, Valhalla, NY 10595 USA. EM arthur_cooper@nymc.edu RI Cooper, Arthur/H-5171-2016 FU NIA NIH HHS [P01 AG014930, P01 AG014930-04, P01 AG014930-08, P01 AG14930] NR 43 TC 31 Z9 32 U1 0 U2 0 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 JUL PY 2008 VL 106 IS 1 BP 37 EP 44 DI 10.1111/j.1471-4159.2008.05350.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 313CL UT WOS:000256718600003 PM 18422943 ER PT J AU Lin, Q Yang, J Chen, M Weinstein, LS Sun, Q Li, H AF Lin, Q. Yang, J. Chen, M. Weinstein, L. S. Sun, Q. Li, H. TI Gs alpha signaling regulates asymmetric cell division of cortical progenitors by controlling polarity cues SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 8th Biennial Meeting of the Asia-Pacific-Society-of-Neurochemistry CY JUN 23-26, 2008 CL Shanghai, PEOPLES R CHINA SP Asia Pacific Soc Neurochem C1 [Lin, Q.; Li, H.] Sichuan Univ, Womens & Childrens Hosp, W China Univ Hosp 2, W China Inst Dev & Stem Cell Biol, Chengdu 610064, Sichuan, Peoples R China. [Lin, Q.; Li, H.] Med Coll Georgia, Dept Neurol, Inst Mol Med & Genet, Dev Neurobiol Program, Augusta, GA 30912 USA. [Yang, J.; Sun, Q.] Beijing Proteome Res Ctr, Dept Antibody Engn, Beijing, Peoples R China. [Chen, M.; Weinstein, L. S.] NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 2008 VL 106 SU 1 BP 60 EP 60 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 307WY UT WOS:000256351500140 ER PT J AU Kim, OJ Ariano, MA Namkung, Y Marinec, P Kim, E Han, J Sibley, DR AF Kim, Ok-Jin Ariano, Marjorie A. Namkung, Yoon Marinec, Paul Kim, Eunmi Han, Jian Sibley, David R. TI D(2) dopamine receptor expression and trafficking is regulated through direct interactions with ZIP SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE D(2) dopamine receptor; interacting protein; lysosomes; protein kinase C-zeta interacting protein; trafficking ID PHOSPHOTYROSINE-INDEPENDENT LIGAND; BINDING-PROTEIN; BETA(2)-ADRENERGIC RECEPTORS; PARKINSONS-DISEASE; OXIDATIVE STRESS; DOWN-REGULATION; SH2 DOMAIN; D2; P62; DESENSITIZATION AB We have used the yeast two-hybrid system to identify protein kinase C-zeta interacting protein (ZIP) as a novel interacting protein for the D(2) dopamine receptor (DAR). This interaction was identified by screening a rat brain cDNA library using the third intracellular loop of the D(2) DAR as bait. A partial-length cDNA encoding ZIP was isolated and characterized as specifically interacting with the third intracellular loop of the D(2) DAR, but not with the third intracellular loops of other DAR subtypes. Biochemical confirmation of the ZIP-D(2) DAR interaction was obtained by expressing the full-length ZIP and D(2) DAR proteins in mammalian cells and demonstrating that they could be co-immunoprecipitated. We further showed that ZIP and the D(2) DAR could be co-immunoprecipitated from endogenous brain tissues. Immunohistochemical analyses further revealed that ZIP and the D(2) DAR were extensively co-localized within numerous neurons in various brain regions. ZIP exists as three protein isoforms of varying length, which are derived from alternative RNA splicing. All three isoforms were found to interact with the D(2) DAR, which allowed for the delineation of the receptor interacting domain to within 38 residues of ZIP. Functionally, over-expression of ZIP was found to result in decreased expression of the D(2) DAR with a corresponding decrease in receptor modulation of cAMP accumulation. Confocal microscopy revealed that ZIP over-expression also lead to an intracellular accumulation of D(2) DAR protein in lysosome compartments. These results suggest that ZIP can physically interact with the D(2) DAR leading to increased intracellular trafficking to lysosomes with subsequent down-regulation of receptor expression and function. C1 [Kim, Ok-Jin] Univ Kansas, Dept Pharmacol & Toxicol, Sch Pharm, Lawrence, KS 66045 USA. [Ariano, Marjorie A.] Rosalind Franklin Univ Med Sci, Chicago Med Sch, Dept Neurosci, N Chicago, IL USA. [Namkung, Yoon; Marinec, Paul; Kim, Eunmi; Han, Jian; Sibley, David R.] NINDS, Mol Neuropharmacol Sect, Natl Inst Hlth, Bethesda, MD USA. RP Kim, OJ (reprint author), Univ Kansas, Dept Pharmacol & Toxicol, Sch Pharm, 5060 Malott Hall,1251 Wescoe Hall Dr Lawrence, Lawrence, KS 66045 USA. EM jokim@ku.edu FU Intramural NIH HHS [Z01 NS003028-01] NR 41 TC 20 Z9 20 U1 0 U2 0 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 JUL PY 2008 VL 106 IS 1 BP 83 EP 95 DI 10.1111/j.1471-4159.2008.05348.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 313CL UT WOS:000256718600007 PM 18346199 ER PT J AU Tanda, G Kopajtic, TA Katz, JL AF Tanda, Gianluigi Kopajtic, Theresa A. Katz, Jonathan L. TI Cocaine-like neurochemical effects of antihistaminic medications SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE chlorpheniramine; cocaine; diphenhydramine; dopamine; histamine H1 antagonists; nucleus accumbens shell ID HISTAMINE H-1 ANTAGONISTS; MESOLIMBIC DOPAMINE TRANSMISSION; NUCLEUS-ACCUMBENS; LOCAL-ANESTHETICS; RHESUS-MONKEYS; EXTRACELLULAR DOPAMINE; RECEPTOR BLOCKADE; PLACE PREFERENCE; DIPHENHYDRAMINE; RATS AB The pattern of activation of dopamine (DA) neurotransmission in the nucleus accumbens (NAc) of rats produced by H(1) histamine antagonists which have behavioral effects like those of psychostimulant drugs was examined. Diphenhydramine and (+)-chlorpheniramine were compared with triprolidine, a potent and selective H(1) antagonist and (-)-chlorpheniramine which is less active than its enantiomer at H(1) receptors. Affinities of the drugs to DA, serotonin, and norepinephrine transporters at H(1) receptors and potencies for DA uptake inhibition in striatal synaptosomes were determined to assess mechanisms by which the compounds increased DA levels. Intravenous diphenhydramine (1.0-3.0 mg/kg) (+)- and (-)-chlorpheniramine (1.0-5.6 mg/kg) but not triprolidine (1.0-3.0 mg/kg) elicited a cocaine-like pattern of stimulation of DA transmission with larger effects in the NAc shell than core. The absence of stereospecific effects with chlorpheniramine enantiomers along with the lack of an effect with triprolidine suggest that the effects on DA transmission were not related to H(1) receptor antagonism. Although in vivo potencies were not directly related to DA transporter affinities, it is hypothesized that actions at that site modulated by other actions, possibly those at the serotonin transporter, are primarily responsible for the neurochemical actions of the drugs on DA neurotransmission and might underlie the occasional misuse of these medications. C1 [Tanda, Gianluigi; Kopajtic, Theresa A.; Katz, Jonathan L.] NIDA, Psychobiol Sect, Medicat Discovery Res Branch, Dept Hlth & Human Serv,NIH, Baltimore, MD 21224 USA. RP Tanda, G (reprint author), NIDA, Psychobiol Sect, Medicat Discovery Res Branch, Dept Hlth & Human Serv,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM gtanda@intra.nida.nih.gov RI Tanda, Gianluigi/B-3318-2009; OI Tanda, Gianluigi/0000-0001-9526-9878; Katz, Jonathan/0000-0002-1068-1159 FU Intramural NIH HHS NR 54 TC 29 Z9 29 U1 1 U2 2 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 JUL PY 2008 VL 106 IS 1 BP 147 EP 157 DI 10.1111/j.1471-4159.2008.05361.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 313CL UT WOS:000256718600012 PM 18363822 ER PT J AU Harry, GJ d'Hellencourt, CL McPherson, CA Funk, JA Aoyama, M Wine, RN AF Harry, G. Jean d'Hellencourt, Christian Lefebvre McPherson, Christopher A. Funk, Jason A. Aoyama, Mineyoshi Wine, Robert N. TI Tumor necrosis factor p55 and p75 receptors are involved in chemical-induced apoptosis of dentate granule neurons SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE apoptosis; hippocampus; microglia; neuroinflammation; trimethyltin; tumor necrosis factor ID KAPPA-B ACTIVATION; SIGNAL-TRANSDUCTION PATHWAYS; CEREBRAL-ARTERY OCCLUSION; TNF RECEPTORS; FACTOR-ALPHA; BRAIN-INJURY; CELL-DEATH; MICE LACKING; MICROGLIAL ACTIVATION; DIVERGENT ROLES AB Localized tumor necrosis factor-alpha (TNF alpha) elevation has diverse effects in brain injury often attributed to signaling via TNFp55 or TNFp75 receptors. Both dentate granule cells and CA pyramidal cells express TNF receptors (TNFR) at low levels in a punctate pattern. Using a model to induce selective death of dentate granule cells (trimethyltin; 2 mg/kg, i.p.), neuronal apoptosis [terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ end labeling, active caspase 3 (AC3)] was accompanied by amoeboid microglia and elevated TNF alpha mRNA levels. TNFp55R (55 kDa type-1 TNFR) and TNFp75R (75 kDa type-2 TNFR) immunoreactivity in AC3(+) neurons displayed a pattern suggestive of receptor internalization and a temporal sequence of expression of TNFp55R followed by TNFp75R associated with the progression of apoptosis. A distinct ramified microglia response occurred around CA1 neurons and healthy dentate neurons that displayed an increase in the normal punctate pattern of TNFRs. Neuronal damage was decreased with i.c.v. injection of TNF alpha antibody and in TNFp55R-/-p75R-/- mice that showed higher constitutive mRNA levels for interleukin (IL-1 alpha), macrophage inflammatory protein 1-alpha (MIP-1 alpha), TNF alpha, transforming growth factor beta 1, Fas, and TNFRSF6-assoicated via death domain (FADD). TNFp75R-/- mice showed exacerbated injury and elevated mRNA levels for IL-1 alpha, MIP-1 alpha, and TNF alpha. In TNFp55R-/- mice, constitutive mRNA levels for TNF alpha, IL-6, caspase 8, FADD, and Fas-associated phosphatase were higher; IL-1 alpha, MIP-1 alpha, and transforming growth factor beta 1 lower. The mice displayed exacerbated neuronal death, delayed microglia response, increased FADD and TNFp75R mRNA levels, and co-expression of TNFp75R in AC3(+) neurons. The data demonstrate TNFR-mediated apoptotic death of dentate granule neurons utilizing both TNFRs and suggest a TNFp75R-mediated apoptosis in the absence of normal TNFp55R activity. C1 [Harry, G. Jean; d'Hellencourt, Christian Lefebvre; McPherson, Christopher A.; Funk, Jason A.; Aoyama, Mineyoshi; Wine, Robert N.] NIEHS, Dept Hlth & Human Serv, Neurotoxicol Grp, Neurobiol Lab,NIH, Res Triangle Pk, NC 27709 USA. RP Harry, GJ (reprint author), NIEHS, Dept Hlth & Human Serv, Neurotoxicol Grp, Neurobiol Lab,NIH, POB 12233,MD C1-04, Res Triangle Pk, NC 27709 USA. EM harry@niehs.nih.gov FU Intramural NIH HHS; NIEHS NIH HHS [N01-ES-65554] NR 66 TC 39 Z9 40 U1 0 U2 3 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 JUL PY 2008 VL 106 IS 1 BP 281 EP 298 DI 10.1111/j.1471-4159.2008.05382.x PG 18 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 313CL UT WOS:000256718600024 PM 18373618 ER PT J AU Shin, YK Martin, B Golden, E Dotson, CD Maudsley, S Kim, W Jang, HJ Mattson, MP Drucker, DJ Egan, JM Munger, SD AF Shin, Y. -K. Martin, B. Golden, E. Dotson, C. D. Maudsley, S. Kim, W. Jang, H. -J. Mattson, M. P. Drucker, D. J. Egan, J. M. Munger, S. D. TI Modulation of taste sensitivity by GLP-1 signaling SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE glucagon-like peptide-1; gustducin; paracrine signaling; serotonin; sweet; taste ID GLUCAGON-LIKE PEPTIDE-1; RAT CIRCUMVALLATE PAPILLAE; MAMMALIAN TASTE; RECEPTOR-CELLS; SWEET TASTE; GASTROINTESTINAL-TRACT; BITTER TASTE; COEXPRESSION PATTERNS; TRANSIENT RECEPTOR; ALPHA-GUSTDUCIN AB In many sensory systems, stimulus sensitivity is dynamically modulated through mechanisms of peripheral adaptation, efferent input, or hormonal action. In this way, responses to sensory stimuli can be optimized in the context of both the environment and the physiological state of the animal. Although the gustatory system critically influences food preference, food intake and metabolic homeostasis, the mechanisms for modulating taste sensitivity are poorly understood. In this study, we report that glucagon-like peptide-1 (GLP-1) signaling in taste buds modulates taste sensitivity in behaving mice. We find that GLP-1 is produced in two distinct subsets of mammalian taste cells, while the GLP-1 receptor is expressed on adjacent intragemmal afferent nerve fibers. GLP-1 receptor knockout mice show dramatically reduced taste responses to sweeteners in behavioral assays, indicating that GLP-1 signaling normally acts to maintain or enhance sweet taste sensitivity. A modest increase in citric acid taste sensitivity in these knockout mice suggests GLP-1 signaling may modulate sour taste, as well. Together, these findings suggest a novel paracrine mechanism for the regulation of taste function. C1 [Shin, Y. -K.; Martin, B.; Golden, E.; Maudsley, S.; Kim, W.; Jang, H. -J.; Mattson, M. P.; Egan, J. M.] Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA. [Dotson, C. D.; Munger, S. D.] NIA, NIH, Baltimore, MD 21224 USA. [Drucker, D. J.] Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Dept Med, Toronto, ON M5G 1X5, Canada. Univ Toronto, Banting & Best Diabet Ctr, Toronto, ON M5G 1L5, Canada. RP Munger, SD (reprint author), Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA. EM eganj@grc.nia.nih.gov; smung001@umaryland.edu RI Mattson, Mark/F-6038-2012; Drucker, Daniel/A-4092-2010; jang, hyeung jin/C-8022-2013; Marion-Poll, Frederic/D-8882-2011 OI Marion-Poll, Frederic/0000-0001-6824-0180 FU Intramural NIH HHS [Z01 AG000318-01]; NIDCD NIH HHS [DC000054, DC005786, DC008301, R01 DC005786, R01 DC008301, T32 DC000054]; NIDCR NIH HHS [DE007309, T32 DE007309] NR 53 TC 129 Z9 135 U1 1 U2 9 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 JUL PY 2008 VL 106 IS 1 BP 455 EP 463 DI 10.1111/j.1471-4159.2008.05397.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 313CL UT WOS:000256718600038 PM 18397368 ER PT J AU Samuel, W Kutty, RK Sekhar, S Vijayasarathy, C Wiggert, B Redmond, TM AF Samuel, William Kutty, R. Krishnan Sekhar, Sonia Vijayasarathy, Camasamudram Wiggert, Barbara Redmond, T. Michael TI Mitogen-activated protein kinase pathway mediates N-(4-hydroxyphenyl)retinamide-induced neuronal differentiation in the ARPE-19 human retinal pigment epithelial cell line SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE activator protein-1; calretinin; c-fos; c-jun; c-jun N-terminal kinase; extracellular signal-regulated kinase; retinal pigment epithelium; stress-activated protein kinase ID A DESATURASE EXPRESSION; NERVE GROWTH-FACTOR; NEURITE OUTGROWTH; DEVELOPMENTAL EXPRESSION; JNK PATHWAY; PC12 CELLS; STEM-CELLS; C-JUN; ACID; APOPTOSIS AB We have shown previously that N-(4-hydroxyphenyl)retinamide (4HPR, fenretinide), a retinoic acid derivative, induces neuronal differentiation in cultured human retinal pigment epithelial (RPE) cells [Chen et al., J. Neurochem., 84 (2003), 972]. We asked the question whether the mitogen-activated protein kinase (MAPK) pathway is involved in the regulation of the 4HPR-induced neuronal differentiation of RPE (ARPE-19) cells. When we treated ARPE-19 cells with 4HPR, c-Raf and MEK1/2 kinase were activated resulting in activation of the downstream effector ERK1/2 and of SAPK/JNK. By blocking the upstream kinase MEK1/2 with specific inhibitor U0126 we abrogated the 4HPR-induced phosphorylation of ERK1/2 and SAPK/JNK, indicating that the neuronal differentiation occurs through a positive cross-talk between the ERK and the SAPK/JNK pathways. Both U0126 and the suppression of ERK1/2 expression with small interfering RNA effectively blocked the 4HPR-induced neuronal differentiation of RPE cells and the expression of calretinin. The activated ERK1/2 then induced a sequential activation of p90RSK, and increase in phosphorylation of transcription factors c-fos and c-jun leading to transcriptional activation of AP-1. Taken together, our results clearly demonstrate that c-Raf/MEK1/2 signaling cascade involving ERK1/2 plays a central role in mediating the 4HPR-induced neuronal differentiation and calretinin expression in the human ARPE-19 retinal pigment epithelial cell line. C1 [Samuel, William] NEI, NIH, LRCMB, Bethesda, MD 20892 USA. [Vijayasarathy, Camasamudram] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. RP Samuel, W (reprint author), NEI, NIH, LRCMB, Bldg 7 Room 329,7 Mem Dr, Bethesda, MD 20892 USA. EM samuelw@nei.nih.gov FU Intramural NIH HHS [Z99 EY999999] NR 50 TC 7 Z9 8 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 2008 VL 106 IS 2 BP 591 EP 602 DI 10.1111/j.1471-4159.2008.05409.x PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 327CU UT WOS:000257708000009 PM 18410500 ER PT J AU Holmes, FE Arnott, N Vanderplank, P Kerr, NCH Longbrake, EE Popovich, PG Imai, T Combadiere, C Murphy, PM Wynick, D AF Holmes, Fiona E. Arnott, Nighat Vanderplank, Penny Kerr, Niall C. H. Longbrake, Erin E. Popovich, Philip G. Imai, Toshio Combadiere, Christophe Murphy, Philip M. Wynick, David TI Intra-neural administration of fractalkine attenuates neuropathic pain-related behaviour SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE CX3CL1; CX3CR1; dorsal root ganglia; fractalkine; nerve injury; neuropathic pain ID NECROSIS-FACTOR-ALPHA; DORSAL-ROOT GANGLIA; PRIMARY NOCICEPTIVE NEURONS; SPARED NERVE INJURY; RAT SCIATIC-NERVE; SPINAL-CORD; CHEMOKINE RECEPTORS; CHEMOTACTIC RECEPTOR; EXPRESSION; MOUSE AB There is increasing evidence that a number of cytokines and their receptors are involved in the processes that lead to the development and maintenance of neuropathic pain states. Here we demonstrate that levels of CX3CR1 (the receptor for the chemokine fractalkine) mRNA in lumbar dorsal root ganglia (DRG) increase 5.8-fold 7 days after sciatic nerve axotomy, and 1.7- and 2.9-fold, 3 and 7 days respectively, after the spared nerve injury (SNI) model of neuropathic pain. In contrast, no significant change in the levels of fractalkine mRNA is apparent in the DRG after axotomy or SNI. The increase in CX3CR1 mRNA is paralleled by a 3.9- and 2.1-fold increase in the number of CX3CR1-positive macrophages in the DRG 7 days after axotomy and SNI, respectively. Expression of CX3CR1 in macrophages is also markedly increased in the sciatic nerve proximal to site of injury, by 25.7-fold after axotomy and 16.2-fold after SNI, 7 days after injury. Intra-neural injection into the sciatic nerve of 400 ng or 100 ng of fractalkine in adult 129OlaHsd mice significantly delayed the development of allodynia for 3 days following SNI. Further, CX3CR1 knockout (KO) mice display an increase in allodynia for three weeks after SNI compared to strain-matched Balb/c controls. Taken together, these results suggest an anti-allodynic role for fractalkine and its receptor in the mouse. C1 [Holmes, Fiona E.] Univ Bristol, Sch Med Sci, Dept Physiol & Pharmacol, Bristol BS8 1TD, Avon, England. [Holmes, Fiona E.; Arnott, Nighat; Vanderplank, Penny; Kerr, Niall C. H.; Wynick, David] Univ Bristol, Dept Clin Sci S Bristol, Bristol BS8 1TD, Avon, England. [Longbrake, Erin E.; Popovich, Philip G.] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Ctr Brain & Spinal Cord Repair, Columbus, OH 43210 USA. [Imai, Toshio] KAN Res Inst, Kyoto, Japan. [Combadiere, Christophe] Univ Paris 06, INSERM, Lab Immunol Cellulaire, Assistance Publ Hop Paris,U543, Paris, France. [Combadiere, Christophe] Univ Paris 06, Fac Med, Paris, France. [Murphy, Philip M.] NIAID, NIH, Bethesda, MD 20892 USA. RP Holmes, FE (reprint author), Univ Bristol, Sch Med Sci, Dept Physiol & Pharmacol, Univ Walk, Bristol BS8 1TD, Avon, England. EM F.E.Holmes@bristol.ac.uk RI Popovich, Phillip/C-9187-2009; Combadiere, Christophe/I-5639-2013; OI Popovich, Phillip/0000-0003-1329-7395; Combadiere, Christophe/0000-0002-1755-4531; Longbrake, Erin/0000-0002-1179-3937 FU Medical Research Council [, G0300028, G0300028(65120)] NR 64 TC 27 Z9 28 U1 0 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 2008 VL 106 IS 2 BP 640 EP 649 DI 10.1111/j.1471-4159.2008.05419.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 327CU UT WOS:000257708000013 PM 18410510 ER PT J AU Montague, D Weickert, CS Tomaskovic-Crook, E Rothmond, DA Kleinman, JE Rubinow, DR AF Montague, D. Weickert, C. S. Tomaskovic-Crook, E. Rothmond, D. A. Kleinman, J. E. Rubinow, D. R. TI Oestrogen receptor alpha localisation in the prefrontal cortex of three mammalian species SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE oestrogen receptor; brain; human post-mortem; monkey; rat ID RANDOMIZED CONTROLLED-TRIAL; HEALTH INITIATIVE MEMORY; CENTRAL-NERVOUS-SYSTEM; FEMALE RHESUS-MONKEYS; MESSENGER-RNA; CEREBRAL-CORTEX; ER-BETA; POSTMENOPAUSAL WOMEN; GENE-EXPRESSION; FRONTAL-CORTEX AB Oestrogen modulates cognitive function and affective behaviours subserved by the prefrontal cortex (PFC). Identifying and localising oestrogen receptor (ER)alpha, in human PFC will contribute to our understanding of the molecular mechanism of oestrogen action in this region. Inferences about the site of action of oestrogen in human brain are derived largely from studies performed in nonhuman mammalian species; however, the congruence of findings across species has not been demonstrated. Furthermore, the laminar, cellular, and subcellular localisation of ER alpha in the cortex is debated. Therefore, we compared the distribution of ER alpha in human dorsolateral prefrontal cortex (DLPFC) with that of monkey DLPFC and rat medial PFC. Immunohistochemistry performed on frontal cortex from the three species demonstrated ER alpha positive cells throughout all layers of the PFC, in pyramidal and nonpyramidal neurones, with both nuclear and cytoplasmic immunoreactivity. Western blot analyses and preabsorption studies confirmed that the antibody used recognised ER alpha and not ER beta. A strong ER alpha immunoreactive band corresponding to the full-length ER alpha protein (65-67 kDa) in the frontal cortex of all three species matched the size of the predominant immunoreactive band detected in breast cancer cell lines known to express ER alpha. Additionally, other ER alpha immunoreactive proteins of varying molecular weight in breast cancer cells, rat ovary and mammalian brain were detected, suggesting that ER alpha may exist in more than one form in the mammalian frontal cortex. The present study provides evidence that ER alpha protein exists in neurones in mammalian PFC and that ER alpha is anatomically well-positioned to directly mediate oestrogen action in these neurones. C1 [Montague, D.; Rubinow, D. R.] NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. [Montague, D.; Weickert, C. S.; Tomaskovic-Crook, E.; Rothmond, D. A.; Kleinman, J. E.] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. [Weickert, C. S.] Prince Wales Med Res Inst, MacQuaric Grp Chair, Schizophrenia Res Inst, Randwick, NSW 2031, Australia. [Tomaskovic-Crook, E.] Univ Melbourne, Ludwig Inst Canc Res, Melbourne, Vic, Australia. [Rubinow, D. R.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. RP Weickert, CS (reprint author), Prince Wales Med Res Inst, MacQuaric Grp Chair, Schizophrenia Res Inst, Barker & Easy St, Randwick, NSW 2031, Australia. EM c.weickert@powmri.edu.au RI Shannon Weickert, Cynthia/G-3171-2011; Tomaskovic-Crook, Eva/C-9339-2016 OI Tomaskovic-Crook, Eva/0000-0002-7818-9013 FU Intramural NIH HHS [Z01 MH002864-03, Z01 MH002399-18] NR 46 TC 49 Z9 49 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD JUL PY 2008 VL 20 IS 7 BP 893 EP 903 DI 10.1111/j.1365-2826.2008.01743.x PG 11 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 315CV UT WOS:000256856400001 PM 18445128 ER PT J AU Sander, T Sprenger, A Machner, B Rambold, H Helmchen, C AF Sander, T. Sprenger, A. Machner, B. Rambold, H. Helmchen, C. TI Disjunctive saccades during smooth pursuit eye movements in ocular myasthenia gravis SO JOURNAL OF NEUROLOGY LA English DT Letter C1 [Sander, T.; Sprenger, A.; Machner, B.; Helmchen, C.] Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. [Rambold, H.] NEI, Bethesda, MD 20892 USA. RP Sander, T (reprint author), Med Univ Lubeck, Dept Neurol, Ratzeburger Allee 160, D-23538 Lubeck, Germany. EM thurid.sander@neuro.uni-luebeck.de RI Sprenger, Andreas/C-7612-2009; OI Sprenger, Andreas/0000-0001-9255-7911; Rambold, Holger/0000-0002-8056-9429 NR 7 TC 0 Z9 0 U1 0 U2 0 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD JUL PY 2008 VL 255 IS 7 BP 1094 EP 1096 DI 10.1007/s00415-008-0843-5 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 331PQ UT WOS:000258025000027 PM 18500494 ER PT J AU Wu, T Hallett, M AF Wu, T. Hallett, M. TI Neural correlates of dual task performance in patients with Parkinson's disease SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID FUNCTIONAL NEUROANATOMY; AUTOMATIC MOVEMENTS; ANTERIOR CINGULATE; WORKING-MEMORY; FRONTAL-CORTEX; MOTOR; INTERFERENCE; RESOURCES; ATTENTION; BRAIN AB Background: Patients with Parkinson's disease (PD) have great difficulty in performing two tasks simultaneously, but the neural contribution to this problem has not been identified. In the current study, we investigated the pathophysiology of dual task performance in PD. Methods: We studied 15 patients with PD and 14 healthy controls. Functional MRIs were obtained before and after practicing dual tasks with different complexities. Results: After practice, 12 normal subjects performed all dual tasks correctly. Twelve patients performed the simpler dual tasks correctly. However, only 3 patients could perform the more complex dual task correctly. Dual tasks activated similar brain regions in both groups. The bilateral precuneus was additionally activated during performance of dual tasks compared with the component tasks in both groups. Patients had greater activity in the cerebellum, premotor area, parietal cortex, precuneus and prefrontal cortex compared with normal subjects. Conclusions: Difficulty in performing two tasks simultaneously in patients with PD is probably due to limited attentional resources, defective central executive function and less automaticity in performing the tasks. Practice can diminish dual task interference and improve performance in patients with PD. C1 [Wu, T.] Capital Med Univ, Xuanwu Hosp, Beijing Inst Geriatr,Dept Neurol, State Key Lab Cognit Neurosci & Learning, Beijing, Peoples R China. [Wu, T.; Hallett, M.] Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, Med Neurol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), Bldg 10,Rm 5N226,10 Ctr Dr MSC 1428, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov FU Intramural NIH HHS NR 40 TC 77 Z9 82 U1 2 U2 13 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD JUL PY 2008 VL 79 IS 7 BP 760 EP 766 DI 10.1136/jnnp.2007.126599 PG 7 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 314LI UT WOS:000256810500007 PM 18006652 ER PT J AU Kerr, PB Oldfield, EH AF Kerr, P. Benjamin Oldfield, Edward H. TI Sublabial-endonasal approach to the sella turcica SO JOURNAL OF NEUROSURGERY LA English DT Article DE endonasal route; exposure; sella turcica; sublabial route; transsphenoidal route ID PARASELLAR REGION; SURGERY; TUMORS AB In this paper the authors describe the sublabial-endonasal-transsphenoidal approach to the sella turcica, a modification that combines elements of the sublabial-submucosal-transseptal approach and the endonasal approach. It provides a midline, or near midline, trajectory, wide exposure of the sella, and secure speculum placement on the osseous edge of the pyriform apenure, while avoiding dissection of the nasal mucosa, and it can be used for microscopic and endoscopic surgery. C1 [Kerr, P. Benjamin; Oldfield, Edward H.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Kerr, P. Benjamin] George Washington Univ, Dept Neurol Surg, Washington, DC USA. RP Oldfield, EH (reprint author), Univ Virginia Hlth Syst, Dept Neurol Surg, POB 800212, Charlottesville, VA 22908 USA. EM eho4u@virginia.edu NR 8 TC 10 Z9 10 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JUL PY 2008 VL 109 IS 1 BP 153 EP 155 DI 10.3171/JNS/2008/109/7/0153 PG 3 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 319YS UT WOS:000257201500026 PM 18590448 ER PT J AU Haselkorn, ML Shellington, D Jackson, E Vagni, V Feldman, K Dubey, R Gillespie, D Bell, M Clark, R Jenkins, L Schnermann, J Homanics, G Kochanek, P AF Haselkorn, M. Lee Shellington, David Jackson, Edwin Vagni, Vincent Feldman, Keri Dubey, Raghvendra Gillespie, Delbert Bell, Michael Clark, Robert Jenkins, Larry Schnermann, Jurgen Homanics, Gregg Kochanek, Patrick TI Adenosine A1 receptor activation as a brake on neuroinflammation after experimental traumatic brain injury in mice SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 26th Annual National-Neurotrauma-Society Symposium CY JUL 27-30, 2008 CL Orlando, FL SP Natl Neurotrauma Soc C1 [Haselkorn, M. Lee; Shellington, David; Jackson, Edwin; Vagni, Vincent; Feldman, Keri; Dubey, Raghvendra; Gillespie, Delbert; Bell, Michael; Clark, Robert; Jenkins, Larry; Homanics, Gregg; Kochanek, Patrick] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Schnermann, Jurgen] NIDDK, NIH, Bethesda, MD USA. RI Kochanek, Patrick/D-2371-2015 OI Kochanek, Patrick/0000-0002-2627-913X NR 0 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD JUL PY 2008 VL 25 IS 7 MA P192 BP 901 EP 901 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 326BX UT WOS:000257634000201 ER PT J AU Walls, ZF Puttaraju, M Temple, GF Gambhir, SS AF Walls, Zachary F. Puttaraju, M. Temple, Gary F. Gambhir, Sanjiv S. TI A generalizable strategy for imaging pre-mRNA levels in living subjects using spliceosome-mediated RNA trans-splicing SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE molecular biology; molecular imaging; animal imaging; RNA; trans-splicing ID POSITRON-EMISSION-TOMOGRAPHY; GENE-EXPRESSION; ADENOASSOCIATED VIRUS; PROTEIN FUNCTION; REPORTER GENE; IN-VIVO; DNA; OLIGONUCLEOTIDES; SMART(TM); DELIVERY AB Molecular imaging of gene expression is currently hindered by the lack of a generalizable platform for probe design. For any gene of interest, a probe that targets protein levels must often be generated empirically. Targeting gene expression at the level of mRNA, however, would allow probes to be built on the basis of sequence information alone. Presented here is a class of generalizable probes that can image pre-mRNA in a sequence-specific manner, using signal amplification and a facile method of delivery. Methods: Pre-trans-splicing molecules (PTMs) were engineered to capitalize on the phenomenon of spliceosome-mediated RNA trans-splicing. Using a modular binding domain that confers specificity by base-pair complementarity to the target pre-mRNA, PTMs were designed to target a chimeric target mini gene and trans-splice the Renilla luciferase gene onto the end of the target. PTMs and target genes were transfected in cell culture and assessed by luciferase assay, reverse-transcriptase polymerase chain reaction, Western blot, and rapid analysis of 5' cDNA ends. PTMs and target genes were also assessed in vivo by hydrodynamic delivery in mice. Results: Efficiency and specificity of the trans-splicing reaction were found to vary depending on the binding domain length and structure. Specific trans-splicing was observed in living animals (P = 0.0862, Kruskal-Wallis test). Conclusion: Described here is a model system used to demonstrate the feasibility of spliceosome-mediated RNA trans-splicing for imaging gene expression at the level of pre-mRNA using optical imaging techniques in living animals. The experiments reported here show proof of principle for a generalizable imaging probe against RNA that can amplify signal on detection and be delivered using existing gene delivery methodology. C1 [Gambhir, Sanjiv S.] Stanford Univ, Sch Med, Biox Program, Dept Radiol, Stanford, CA 94305 USA. [Temple, Gary F.] NHGRI, MGC, Natl Inst Hlth, Bethesda, MD 20892 USA. [Puttaraju, M.] VIRxSYS Corp, Gaithersburg, MD USA. [Walls, Zachary F.] Univ Calif Los Angeles, Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA USA. RP Gambhir, SS (reprint author), Stanford Univ, Sch Med, Biox Program, Dept Radiol, 318 Campus Dr,Clark E150, Stanford, CA 94305 USA. EM sgambhir@stanford.edu RI Walls, Zachary/F-1942-2011 OI Walls, Zachary/0000-0001-8642-846X NR 30 TC 4 Z9 4 U1 1 U2 1 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 JUL PY 2008 VL 49 IS 7 BP 1146 EP 1154 DI 10.2967/jnumed.107.047662 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 325PB UT WOS:000257599700021 PM 18552150 ER PT J AU Rantz, MJ Aud, MA Alexander, G Wakefield, BJ Skubic, M Luke, RH Anderson, D Keller, MM AF Rantz, Marilyn J. Aud, Myra A. Alexander, Greg Wakefield, Bonnie J. Skubic, Marjorie Luke, Robert H. Anderson, Derek Keller, Msjames M. TI Falls, technology, and stunt actors - New approaches to fall detection and fall risk assessment SO JOURNAL OF NURSING CARE QUALITY LA English DT Editorial Material C1 [Rantz, Marilyn J.; Aud, Myra A.; Alexander, Greg; Wakefield, Bonnie J.] Univ Missouri, Sinclair Sch Nursing, Columbia, MO 65211 USA. [Rantz, Marilyn J.] Univ Missouri, Family & Community Med, Sch Med, Columbia, MO 65211 USA. [Skubic, Marjorie; Luke, Robert H.; Anderson, Derek; Keller, Msjames M.] Univ Missouri, Dept Elect & Comp Engn, Columbia, MO 65211 USA. [Skubic, Marjorie; Keller, Msjames M.] Univ Missouri, Coll Engn, Columbia, MO 65211 USA. [Luke, Robert H.; Anderson, Derek] Univ Missouri, Natl Lib Med, Columbia, MO 65211 USA. RP Rantz, MJ (reprint author), Univ Missouri, Sinclair Sch Nursing, Columbia, MO 65211 USA. EM rantzm@missouri.edu OI Alexander, Gregory L/0000-0003-4500-8797 NR 8 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1057-3631 J9 J NURS CARE QUAL JI J. Nurs. Care Qual. PD JUL-SEP PY 2008 VL 23 IS 3 BP 195 EP 201 PG 7 WC Nursing SC Nursing GA 317QM UT WOS:000257034700003 PM 18562859 ER PT J AU Hilton, MF Whiteford, HA Sheridan, JS Cleary, CM Chant, DC Wang, PS Kessler, RC AF Hilton, Michael F. Whiteford, Harvey A. Sheridan, Judith S. Cleary, Catherine M. Chant, David C. Wang, Philip S. Kessler, Ronald C. TI The prevalence of psychological distress in employees and associated occupational risk factors SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID NATIONAL-COMORBIDITY-SURVEY; MENTAL-HEALTH-SURVEY; PERFORMANCE QUESTIONNAIRE HPQ; DSM-IV DISORDERS; PSYCHIATRIC-DISORDER; GENERAL-POPULATION; SURVEY REPLICATION; EMPLOYMENT STATUS; WORK CHARACTERISTICS; ORGANIZATION HEALTH AB Objective: There is limited occupational health industry data pertaining to 1) the prevalence of psychological distress in various employee subtypes and 2) risk factors for employee psychological distress. Method: The employees of 58 large public and private sector employers were invited to complete the Kessler 6 (K6) as part of the Health and Performance at Work Questionnaire. A K6 score of >= 13 was chosen to indicate high psychological distress. Results: Data on 60,556 full-time employees indicate that 4.5% of employees have high psychological distress of which only 22% were in current treatment. Occupational risk factors identified include long working hours, sales staff and non-traditional gender roles. Conclusion: High psychological distress is pervasive across all employee subtypes and remains largely untreated. Risk factors identified will guide the targeting of mental health promotion, prevention and screening programs. C1 [Hilton, Michael F.; Whiteford, Harvey A.; Sheridan, Judith S.; Cleary, Catherine M.; Chant, David C.] Queensland Ctr Mental Hlth Res, Richards, Qld 4077, Australia. [Hilton, Michael F.; Whiteford, Harvey A.] Univ Queensland, Sch Populat Hlth, Herston, Qld, Australia. [Chant, David C.] Univ Queensland, Sch Med, Herston, Qld, Australia. [Wang, Philip S.; Kessler, Ronald C.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Wang, Philip S.] NIMH, Div Serv & Intervent Res, Rockville, MD USA. RP Hilton, MF (reprint author), Queensland Ctr Mental Hlth Res, Locked Bag 500, Richards, Qld 4077, Australia. EM michael_hilton@qcmhr.uq.edu.au RI Whiteford, Harvey/A-4840-2009 OI Whiteford, Harvey/0000-0003-4667-6623 NR 74 TC 49 Z9 49 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD JUL PY 2008 VL 50 IS 7 BP 746 EP 757 DI 10.1097/JOM.0b013e31817e9171 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 327IV UT WOS:000257723700004 PM 18617830 ER PT J AU Mac Crawford, J Hoppin, JA Alavanja, MCR Blair, A Sandler, DP Kamel, F AF Mac Crawford, John Hoppin, Jane A. Alavanja, Michael C. R. Blair, Aaron Sandler, Dale P. Kamel, Freya TI Hearing loss among licensed pesticide applicators in the Agricultural Health Study SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID NEW-YORK FARMERS; OCCUPATIONAL-EXPOSURE; CIGARETTE-SMOKING; ORGANIC-SOLVENTS; RISK-FACTOR; NOISE; EPIDEMIOLOGY; WORKERS; RECEPTORS; COHORT AB Objective: We evaluated self-reported hearing loss and pesticide exposure in licensed private pesticide applicators enrolled in the Agricultural Health Study in 1993 to 1997 in Iowa and North Carolina. Methods: Among 14,229 white male applicators in 1999 to 2003, 4926 reported hearing loss (35%). Logistic regression was performed with adjustment for state, age, and noise, solvents, and metals. We classified pesticides by lifetime days of use. Results: Compared with no exposure, the odds ratio (95% confidence interval) for the highest quartile of exposure was 1.19 (1.04 to 1.35) for insecticides and 1.17 (1.03 to 1.31) for organophosphate insecticides. Odds of hearing loss were elevated for high pesticide exposure events (1.38, 1.25 to 1.54), pesticide related doctor visits (1.38, 1.17 to 1.62) or hospitalization (1.81, 1.25 to 2.62), and diagnosed pesticide poisoning (1.75, 1.36 to 2.26). Conclusions: Although control for exposure to noise or other neurotoxicants was limited, this study extends previous reports suggesting that organophosphate exposure increases risk of hearing loss. C1 [Mac Crawford, John] Ohio State Univ, Coll Publ Hlth, Columbus, OH 43210 USA. [Hoppin, Jane A.; Sandler, Dale P.; Kamel, Freya] Natl Inst Environm Hlth Sci, NIH, Washington, DC USA. [Alavanja, Michael C. R.; Blair, Aaron] Natl Canc Inst, NIH, Washington, DC USA. RP Mac Crawford, J (reprint author), A332A Starling Loving Hall,320 W 10th Ave, Columbus, OH 43210 USA. EM mcrawford@cph.osu.edu OI Kamel, Freya/0000-0001-5052-6615; Sandler, Dale/0000-0002-6776-0018 FU Intramural NIH HHS [Z99 ES999999] NR 36 TC 7 Z9 8 U1 3 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1076-2752 EI 1536-5948 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD JUL PY 2008 VL 50 IS 7 BP 817 EP 826 DI 10.1097/JOM.0b013e31816a8caf PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 327IV UT WOS:000257723700012 PM 18617838 ER PT J AU Madigan, WP Raymond, WR Wroblewski, KJ Thebpatiphat, N Birdsong, RH Jaafar, MS AF Madigan, William P. Raymond, William R. Wroblewski, Keith J. Thebpatiphat, Nuthida Birdsong, Richard H. Jaafar, Mohamad S. TI A review of pediatric uveltis: Part II. Autoimmune diseases and treatment modalities SO JOURNAL OF PEDIATRIC OPHTHALMOLOGY & STRABISMUS LA English DT Review ID INFLAMMATORY-BOWEL-DISEASE; NECROSIS-FACTOR-ALPHA; JUVENILE IDIOPATHIC ARTHRITIS; POSNER-SCHLOSSMAN-SYNDROME; KOYANAGI-HARADA SYNDROME; ACUTE ANTERIOR UVEITIS; ISCHEMIC OPTIC NEUROPATHY; SYMPATHETIC OPHTHALMIA; TUBULOINTERSTITIAL NEPHRITIS; RHEUMATOID-ARTHRITIS AB Uveitis is a manifestation of complex processes that can represent an infectious process or a dysfunction of the immune system that may have grave effects on the eye. Although infectious causes, once properly identified, may be successfully treated by addressing the inciting organism with recognized interventions, the immune-modulated chronic forms of uveitis often provide more complex challenges in management. Recent strides in understanding the inflammatory pathway and better bioengineering capabilities have resulted in some new modalities of treatment. C1 [Madigan, William P.; Thebpatiphat, Nuthida; Jaafar, Mohamad S.] Childrens Natl Med Ctr, Washington, DC 20011 USA. [Raymond, William R.] Madigan Army Med Ctr, Tacoma, WA 98431 USA. [Wroblewski, Keith J.] NEI, NIH, Bethesda, MD 20892 USA. [Birdsong, Richard H.] Walter Reed Army Med Ctr, Washington, DC 20307 USA. RP Madigan, WP (reprint author), Childrens Natl Med Ctr, 111 Michigan Ave NW, Washington, DC 20011 USA. NR 153 TC 6 Z9 6 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0191-3913 J9 J PEDIAT OPHTH STRAB JI J. Pediatr. Ophthalmol. Strabismus. PD JUL-AUG PY 2008 VL 45 IS 4 BP 202 EP 219 PG 18 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA 326VI UT WOS:000257686700003 PM 18705618 ER PT J AU Kahana, S Drotar, D Frazier, T AF Kahana, Shoshana Drotar, Dennis Frazier, Tom TI Meta-analysis of psychological interventions to promote adherence to treatment in pediatric chronic health conditions SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Review DE adherence; chronic health conditions; meta-analysis; pediatric; psychological intervention ID RANDOMIZED CLINICAL-TRIAL; EMPIRICALLY SUPPORTED TREATMENTS; INCREASING CALORIE CONSUMPTION; JUVENILE RHEUMATOID-ARTHRITIS; PEER-GROUP INTERVENTION; 2-YEAR FOLLOW-UP; CYSTIC-FIBROSIS; SELF-MANAGEMENT; METABOLIC-CONTROL; BEHAVIORAL INTERVENTION AB Objective To estimate the effectiveness of adherence-promoting psychological interventions for pediatric populations with chronic health conditions. Methods A meta-analysis was conducted on 70 adherence-promoting psychological intervention studies among chronically ill youth using a weighted least squares approach and random effect model. Results Medium effects sizes were found for the behavioral (mean d=.54, 95% confidence interval [CI] = 0.34-0.73, n = 10) and multi-component interventions (mean d=.51, 95% CI = 0.45-0.57, n = 46), while educational interventions displayed a small effect size with adherence (mean d=.16, 95% CI = 0.10-0.22, n = 23). Study designs incorporating prepost comparisons yielded effect sizes approaching the medium range (mean d=.42, 95% CI = 0.36-0.48, n = 30). Conclusions Behavioral and multi-component interventions appear to be relatively potent in promoting adherence among chronically ill youth. Recommendations for future research and methodological issues are presented. C1 [Kahana, Shoshana; Drotar, Dennis] Cincinnati Childrens Hosp Med Ctr, Ctr Promot Adherence & Self Management, Div Behav Med & Clin Psychol, Cincinnati, OH USA. [Frazier, Tom] Cleveland Clin Fdn, Cleveland, OH 44195 USA. RP Kahana, S (reprint author), NIMH, Div Dev Translat Res, 6001 Execut Blvd,MSC 9617,Room 6190, Bethesda, MD 20892 USA. EM sykahana@gmail.com NR 105 TC 125 Z9 126 U1 7 U2 18 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0146-8693 J9 J PEDIATR PSYCHOL JI J. Pediatr. Psychol. PD JUL PY 2008 VL 33 IS 6 BP 590 EP 611 DI 10.1093/jpepsy/jsm128 PG 22 WC Psychology, Developmental SC Psychology GA 306XT UT WOS:000256282400003 PM 18192300 ER PT J AU Silverstein, FS Jensen, FE Inder, T Hellstrom-Westas, L Hirtz, D Ferriero, DM AF Silverstein, Faye S. Jensen, Frances E. Inder, Terrie Hellstrom-Westas, Lena Hirtz, Deborah Ferriero, Donna M. TI Improving the treatment of neonatal seizures: National Institute of Neurological Disorders and Stroke workshop report SO JOURNAL OF PEDIATRICS LA English DT Article ID AMPLITUDE-INTEGRATED ELECTROENCEPHALOGRAPHY; CEREBRAL FUNCTION MONITOR; ELECTROGRAPHIC SEIZURES; SILENT SEIZURES; NEWBORN-INFANTS; TERM NEWBORNS; BRAIN; INJURY C1 [Silverstein, Faye S.] Univ Michigan, Dept Pediat & Neurol, Ann Arbor, MI 48109 USA. [Jensen, Frances E.] Harvard Univ, Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Inder, Terrie] Washington Univ, Dept Pediat, St Louis, MO 63130 USA. [Hellstrom-Westas, Lena] Uppsala Univ, Dept Pediat, Uppsala, Sweden. [Hirtz, Deborah] NINDS, NIH, Bethesda, MD USA. [Ferriero, Donna M.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. RP Silverstein, FS (reprint author), Univ Michigan, Dept Pediat & Neurol, 1150 W Med Ctr Dr,Room 8301, Ann Arbor, MI 48109 USA. EM fsilvers@med.umich.edu NR 20 TC 30 Z9 32 U1 0 U2 2 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 JUL PY 2008 VL 153 IS 1 BP 12 EP 15 DI 10.1016/j.jpeds.2008.01.041 PG 4 WC Pediatrics SC Pediatrics GA 319HN UT WOS:000257154800006 PM 18571526 ER PT J AU Goker-Alpan, O Wiggs, EA Eblan, MJ Benko, W Ziegler, SG Sidransky, E Schiffmann, R AF Goker-Alpan, Ozlem Wiggs, Edythe A. Eblan, Michael J. Benko, William Ziegler, Shira G. Sidransky, Ellen Schiffmann, Raphael TI Cognitive outcome in treated patients with chronic neuronopathic Gaucher disease SO JOURNAL OF PEDIATRICS LA English DT Article ID ENZYME REPLACEMENT THERAPY; EPILEPSY; TYPE-3; GLUCOCEREBROSIDASE; PHENOTYPE; GENOTYPE; MARKER AB Objective To investigate the spectrum and prevalence of cognitive deficits among children with type 3 (chronic neuronopathic) Gaucher disease (GD). Study design A case review study identified 32 children (male/female; 17:15) with type 3 GD who had received enzyme replacement therapy (ERT) or a bone marrow transplant. The diagnosis of GD was established by enzymatic assay and DNA testing. Subjects were assessed with standard neuropsychological testing, and data from the most recent evaluation were included. Results Neuropsychometric assessments demonstrated a wide spectrum of full-scale IQ scores ranging from 39 to 124 (mean 75). About 60% of subjects had intellectual skills below average. There were significant discrepancies between verbal and performance IQ, with a range between -6 and 38 points (P =.02). This gap was more prominent in older subjects, with better performance in the verbal areas. No correlation was observed between intelligence measures and genotype or the extent of systemic involvement. The dosage, age at initiation, and the length of ERT had no significant effect on IQ scores. Conclusions in type 3 GD, cognitive deficits, characterized by visual-spatial dysfunction, are common but underappreciated and appear resistant to ERT. C1 [Goker-Alpan, Ozlem; Eblan, Michael J.; Ziegler, Shira G.; Sidransky, Ellen] NHGRI, Sect Neurogenet, Med Genet Branch, Bethesda, MD 20892 USA. [Wiggs, Edythe A.; Benko, William; Schiffmann, Raphael] NINDS, Dev & Metab Neurol Branch, Bethesda, MD 20892 USA. RP Sidransky, E (reprint author), NHGRI, Sect Neurogenet, Med Genet Branch, Bldg 35,Room IA213,35 Covenent Dr,MSC 3708, Bethesda, MD 20892 USA. EM sidranse@mail.nih.gov FU Intramural NIH HHS NR 28 TC 10 Z9 10 U1 0 U2 0 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 JUL PY 2008 VL 153 IS 1 BP 89 EP 94 DI 10.1016/j.jpeds.2007.12.023 PG 6 WC Pediatrics SC Pediatrics GA 319HN UT WOS:000257154800023 PM 18571543 ER PT J AU Lateef, TM Tsuchida, TN Chang, T Johnson, J Gaillard, WD Nelson, KB AF Lateef, Tarannum M. Tsuchida, Tammy N. Chang, Taeun Johnson, Jami Gaillard, William D. Nelson, Karin B. TI Diagnostic value of lumbar puncture in afebrile infants with suspected new-onset seizures SO JOURNAL OF PEDIATRICS LA English DT Article ID CEREBROSPINAL-FLUID PLEOCYTOSIS; CHILDREN AB No established guidelines address the need for lumbar puncture in fever-free infants younger than 6 months of age with a first seizure. We analyzed cerebrospinal fluid results in infants and found that lumbar puncture adds little diagnostic value to the evaluation of young, well-appearing infants presenting with possible new-onset seizures. C1 [Lateef, Tarannum M.; Tsuchida, Tammy N.; Chang, Taeun; Johnson, Jami; Gaillard, William D.; Nelson, Karin B.] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. [Lateef, Tarannum M.; Tsuchida, Tammy N.; Chang, Taeun; Johnson, Jami; Gaillard, William D.; Nelson, Karin B.] George Washington Univ, Sch Med, Washington, DC USA. [Gaillard, William D.; Nelson, Karin B.] NINDS, NIH, Bethesda, MD 20892 USA. RP Lateef, TM (reprint author), Childrens Natl Med Ctr, Dept Neurol, 111 Michigan Ave, Washington, DC 20010 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JUL PY 2008 VL 153 IS 1 BP 140 EP 142 DI 10.1016/j.jpeds.2008.02.030 PG 3 WC Pediatrics SC Pediatrics GA 319HN UT WOS:000257154800033 PM 18571553 ER PT J AU Branch-Mays, GL Dawson, DR Gunsolley, JC Reynolds, MA Ebersole, JL Novak, KF Mattison, JA Ingram, DK Novak, MJ AF Branch-Mays, Grishondra L. Dawson, Dolphus R. Gunsolley, John C. Reynolds, Mark A. Ebersole, Jeffrey L. Novak, Karen F. Mattison, Julie A. Ingram, Donald K. Novak, M. John TI The effects of a calorie-reduced diet on periodontal inflammation and disease in a non-human primate model SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE caloric restriction; inflammation; ligature; periodontitis; primate studies ID MONKEYS MACACA-MULATTA; RHESUS-MONKEYS; LIFE-SPAN; FOOD RESTRICTION; ENERGY-BALANCE; MORBIDITY; LONGEVITY; RELEVANCE; HUMANS; MECHANISMS AB Background: Low-calorie diets are commonplace for reducing body weight. However, no information is available on the effects of a reduced-calorie diet on periodontal inflammation and disease. The purpose of this study was to evaluate the clinical effects of a long-term calorie-restriction (CR) diet on periodontitis in an animal model of periodontitis. Methods: Periodontitis was induced in 55 young, healthy, adult rhesus monkeys (Macaca mulatta) by tying 2.0 silk ligatures at the gingival margins of maxillary premolar/molar teeth. Animals on a CR diet (30% CR; N = 23) were compared to ad libitum diet controls (N = 32). Clinical measures, including the plaque index (PI), probing depth (PD), clinical attachment level (CAL), modified gingival index (GI), and bleeding on probing (BOP) were recorded at baseline and 1, 2, and 3 months after ligature placement. Results: Significant effects of CR were observed on the development of inflammation and the progression of periodontal destruction in this model. Compared to controls, CR resulted in a significant reduction in ligature-induced GI (P<0.0001), BOP(P<0.0015), PD (P<0.0016), and CAL (P<0.0038). Periodontal destruction, as measured by CAL, progressed significantly more slowly in the CR animals than in the controls (P<0.001). Conclusions: These clinical findings are consistent with available evidence that CR has anti-inflammatory effects. Moreover, these experimental findings are the first observations, to the best of our knowledge, that CR dampens the inflammatory response and reduces active periodontal breakdown associated with an acute microbial challenge. C1 [Dawson, Dolphus R.; Ebersole, Jeffrey L.; Novak, Karen F.; Novak, M. John] Univ Kentucky, Ctr Oral Hlth Res, Coll Dent, Lexington, KY 40536 USA. [Branch-Mays, Grishondra L.; Reynolds, Mark A.] Univ Maryland, Sch Dent, Dept Periodont, Baltimore, MD 21201 USA. [Gunsolley, John C.] Virginia Commonwealth Univ, Sch Dent, Dept Periodont, Richmond, VA USA. [Mattison, Julie A.] NIA, Lab Expt Gerontol, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Ingram, Donald K.] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Nutr Neurosci & Aging Lab, Baton Rouge, LA USA. RP Novak, MJ (reprint author), Univ Kentucky, Ctr Oral Hlth Res, Coll Dent, 414 Hlth Sci Res Bldg, Lexington, KY 40536 USA. EM mjnova2@uky.edu FU Intramural NIH HHS [Z01 AG000371-02]; NIA NIH HHS [U01 AG 021406, U01 AG021406] NR 38 TC 15 Z9 15 U1 2 U2 5 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD JUL PY 2008 VL 79 IS 7 BP 1184 EP 1191 DI 10.1902/jop.2008.070629 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 326FJ UT WOS:000257643600010 PM 18597600 ER PT J AU Pariser, JJ Partilla, JS Dersch, CM Ananthan, S Rothman, RB AF Pariser, Joseph J. Partilla, John S. Dersch, Christina M. Ananthan, Subramaniam Rothman, Richard B. TI Studies of the biogenic amine transporters. 12. Identification of novel partial inhibitors of amphetamine-induced dopamine release SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID GUINEA-PIG BRAIN; SEROTONIN TRANSPORTER; BINDING-SITE; MODULATION; NOREPINEPHRINE; PAROXETINE; RECEPTOR AB Previous studies identified partial inhibitors and allosteric modulators of 5-hydroxytryptamine ([5-amino-3-(3,4-dichlorophenyl)1,2- dihydropyrido[3,4-b] pyrazin-7-yl] carbamic acid ethyl ester [SoRI-6238], 4-(2-[bis(4-fluorophenyl) methoxy] ethyl)-1-(2-trifluoromethyl- benzyl)-piperidine [TB-1-099]) and dopamine transporters N-(diphenylmethyl)-2-phenyl-4-quinazolinamine, [SoRI-9804]). We report here the identification of three novel allosteric modulators of the dopamine transporter [N-(2,2-diphenylethyl)- 2-phenyl-4-quinazolinamine [SoRI-20040], N-(3,3-diphenylpropyl)- 2-phenyl-4-quinazolinamine [SoRI-20041], and [4-amino-6-[(diphenylmethyl) amino]-5-nitro-2-pyridinyl] carbamic acid ethyl ester [SoRI-2827]]. Membranes were prepared from human embryonic kidney cells expressing the cloned human dopamine transporter (hDAT). [I-125]3 beta-(4'-Iodophenyl)tropan-2 beta-carboxylic acid methyl ester ([I-125]RTI-55) binding and other assays followed published procedures. SoRI-20040, SoRI-20041, and SoRI-2827 partially inhibited [I-125]RTI-55 binding, with EC50 values ranging from similar to 1.4 to 3 mu M and E-max values decreasing as the [I-125]RTI-55 concentrations increased. All three compounds decreased the [I-125]RTI-55 B-max value and increased the apparent K-d value in a manner well described by a sigmoid dose-response curve. In dissociation rate experiments, SoRI-20040 (10 mu M) and SoRI-20041 (10 mu M), but not SoRI-2827 (10 mu M), slowed the dissociation of [I-125] RTI-55 from hDAT by similar to 30%. Using rat brain synaptosomes, all three agents partially inhibited [H-3] dopamine uptake, with EC50 values ranging from 1.8 to 3.1 mu M and decreased the V-max value in a dose-dependent manner. SoRI-9804 and SoRI-20040 partially inhibited amphetamine-induced dopamine transporter-mediated release of [H-3]1-methyl-4-phenylpyridinium ion from rat caudate synaptosomes in a dose-dependent manner. Viewed collectively, we report several compounds that allosterically modulate hDAT binding and function, and we identify novel partial inhibitors of amphetamine-induced dopamine release. C1 [Pariser, Joseph J.; Partilla, John S.; Dersch, Christina M.; Rothman, Richard B.] NIDA, NIH, Clin Psychopharmacol Sect, Dept Hlth & Human Serv,Intramural Res Program, Baltimore, MD 21224 USA. [Ananthan, Subramaniam] So Res Inst, Dept Organ Chem, Birmingham, AL 35255 USA. RP Rothman, RB (reprint author), NIDA, NIH, Clin Psychopharmacol Sect, Dept Hlth & Human Serv,Intramural Res Program, Suite 4500,Triad Bldg,333 Cassell Dr, Baltimore, MD 21224 USA. EM rrothman@mail.nih.gov FU Intramural NIH HHS [Z01 DA000119-16] NR 22 TC 10 Z9 11 U1 1 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 JUL PY 2008 VL 326 IS 1 BP 286 EP 295 DI 10.1124/jpet.108.139675 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 315OM UT WOS:000256889300032 PM 18441249 ER PT J AU Segall-Correa, AM Marin-Leon, L Helito, H Perez-Escamilla, R Santos, LMP Paes-Sousa, R AF Segall-Correa, Ana Maria Marin-Leon, Leticia Helito, Hugo Perez-Escamilla, Rafael Pacheco Santos, Leonor Maria Paes-Sousa, Romulo TI Cash transference and food insecurity in Brazil: analysis of national data SO JOURNAL OF PHYSICAL THERAPY SCIENCE LA Portuguese DT Article DE household survey; proverty; public policy; food security AB Objective The 2004 National Household Survey Data was analyzed to test the hypothesis that cash transference from government social programs is associated with household food security. Methods Secondary data were used from the National Household Sample Survey which interviewed residents of 112,716 households. The present analysis included permanent and temporary private households, where food security items were informed by a resident of the household, restricting the collection of data to households with per capita monthly income of up to I minimum wage, representing 51.2% of the sample. Three models for estimating the amount of cash transference were developed, model 3 was chosen because it was less likely to overestimate effects. To analyze how cash transference affected the prevalence of food security only households that received cash transference were included in the analysis, representing 14.2% of the interviewed households. The association between food security and cash transference, controlled for other independent variables, was estimated using a logistic regression model with stepwise method for each of the three income strata. Results The mean per capita cash transference was of R$81.68 per family. Multiple logistic regression showed an increased chance of food security of 8% per each R$ 10.00 contributed by social programs. Rural residence, male head of household, and Caucasian head of household were factors that also presented a higher chance of food security. Conclusion The hypothesis was confirmed, showing a Positive association between cash transfer and household food security, regardless of the effects of other explanatory factors. C1 [Segall-Correa, Ana Maria; Helito, Hugo] Univ Estadual Campinas, Fac Ciencias Med, Dept Prevent & Social Med, Grp Pesquisa Seguranca Alimentar, BR-13084970 Campinas, SP, Brazil. [Perez-Escamilla, Rafael] Univ Connecticut, NIH Export Ctr Excellence Eliminating Hlth Dispar, Storrs, CT USA. [Pacheco Santos, Leonor Maria] Secretaria Avaliacao & Gestao Informacao, Minist Desenvolvimento Social & Combate Fome, Brasilia, DF, Brazil. [Paes-Sousa, Romulo] Pontificia Univ Catolica Minas Gerais, Programa Posgraduacao Ciencias Sociais, Belo Horizonte, MG, Brazil. Inst Brasileiro Geog & Estat, Artigo Elaborado Partir Anal Secundaria Dados Pes, Rio De Janeiro, Brazil. RP Segall-Correa, AM (reprint author), Univ Estadual Campinas, Fac Ciencias Med, Dept Prevent & Social Med, Grp Pesquisa Seguranca Alimentar, Caixa Postal 6111, BR-13084970 Campinas, SP, Brazil. EM segall@fcm.unicamp.br RI Bhuvanendra, Dharini/I-1207-2012; Segall-Correa, Ana Maria/K-6689-2012 OI Segall-Correa, Ana Maria/0000-0003-0140-064X NR 16 TC 5 Z9 5 U1 1 U2 3 PU SOC PHYSICAL THERAPY SCIENCE PI TOKYO PA C/O PUBLICATION CENTER, 1-24-12 SUGAMO, TOSHIMA-KU, TOKYO, 170-0002, JAPAN SN 0915-5287 J9 J PHYS THER SCI JI J. Phys. Ther. Sci. PD JUL-AUG PY 2008 VL 21 SU S BP 39 EP 51 PG 13 WC Rehabilitation SC Rehabilitation GA 348AE UT WOS:000259182400005 ER PT J AU Putney, JW Bird, GS AF Putney, James W. Bird, Gary S. TI Cytoplasmic calcium oscillations and store-operated calcium influx SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article; Proceedings Paper CT Symposium on Store-Operated Calcium Channels - Mechanism and Function CY FEB 01, 2008 CL Long Beach, CA ID CA2+-SELECTIVE ARC CHANNELS; EMBRYONIC KIDNEY-CELLS; TRPC CATION CHANNELS; SMOOTH-MUSCLE-CELLS; CA2+ RELEASE; CRAC CHANNEL; INOSITOL TRISPHOSPHATE; LOADING DEPENDENCE; PLASMA-MEMBRANE; CYTOSOLIC CA2+ AB Intracellular calcium oscillations have fascinated scientists for decades. They provide an important cellular signal which, unlike most signalling mechanisms, is digitally encoded. While it is generally agreed that oscillations most frequently arise from cyclical release and re-uptake of intracellularly stored calcium, it is becoming increasingly clear that influx of calcium across the plasma membrane also plays a critical role in their maintenance and even in delivering their signal to the correct cellular locus. In this review we will discuss the role played by Ca(2+) entry mechanisms in Ca(2+) oscillations, and approaches to understanding the molecular nature of this Ca(2+) entry pathway. C1 NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Putney, JW (reprint author), NIEHS, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. EM putney@niehs.nih.gov FU Intramural NIH HHS NR 49 TC 55 Z9 59 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JUL 1 PY 2008 VL 586 IS 13 BP 3055 EP 3059 DI 10.1113/jphysiol.2008.153221 PG 5 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 326RB UT WOS:000257675500009 PM 18388136 ER PT J AU Zemkova, HW Bjelobaba, I Tomic, M Zemkova, H Stojilkovic, SS AF Zemkova, Hana W. Bjelobaba, Ivana Tomic, Melanija Zemkova, Hana Stojilkovic, Stanko S. TI Molecular, pharmacological and functional properties of GABA(A) receptors in anterior pituitary cells SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID GAMMA-AMINOBUTYRIC-ACID; THYROTROPIN-RELEASING-HORMONE; PROLACTIN SECRETION; RAT LACTOTROPHS; BOVINE LACTOTROPHS; GROWTH-HORMONE; LUTEINIZING-HORMONE; MEDIATED INHIBITION; COTRANSPORTER KCC2; FROG MELANOTROPHS AB Anterior pituitary cells express gamma-aminobutyric acid (GABA)-A receptor-channels, but their structure, distribution within the secretory cell types, and nature of action have not been clarified. Here we addressed these questions using cultured anterior pituitary cells from postpubertal female rats and immortalized alpha T3-1 and GH(3) cells. Our results show that mRNAs for all GABA(A) receptor subunits are expressed in pituitary cells and that alpha 1/beta 1 subunit proteins are present in all secretory cells. In voltage-clamped gramicidin-perforated cells, GABA induced dose-dependent increases in current amplitude that were inhibited by bicuculline and picrotoxin and facilitated by diazepam and zolpidem in a concentration-dependent manner. In intact cells, GABA and the GABA(A) receptor agonist muscimol caused a rapid and transient increase in intracellular calcium, whereas the GABA(B) receptor agonist baclofen was ineffective, suggesting that chloride-mediated depolarization activates voltage-gated calcium channels. Consistent with this finding, RT-PCR analysis indicated high expression of NKCC1, but not KCC2 cation/chloride transporter mRNAs in pituitary cells. Furthermore, the GABA(A) channel reversal potential for chloride ions was positive to the baseline membrane potential in most cells and the activation of ion channels by GABA resulted in depolarization of cells and modulation of spontaneous electrical activity. These results indicate that secretory pituitary cells express functional GABA(A) receptor-channels that are depolarizing. C1 [Zemkova, Hana W.; Bjelobaba, Ivana; Tomic, Melanija; Zemkova, Hana; Stojilkovic, Stanko S.] NICHD, Sect Cellular Signalling, Program Dev Neurosci, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Stojilkovic, SS (reprint author), NICHD, Sect Cellular Signalling, Program Dev Neurosci, Natl Inst Hlth, Bldg 49,Room 6A-36,49 Convent Dr, Bethesda, MD 20892 USA. EM stankos@helix.nih.gov RI Zemkova, Hana/C-1844-2012; Tomic, Melanija/C-3371-2016 FU Intramural NIH HHS NR 64 TC 13 Z9 14 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JUL 1 PY 2008 VL 586 IS 13 BP 3097 EP 3111 DI 10.1113/jphysiol.2008.153148 PG 15 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 326RB UT WOS:000257675500013 PM 18450776 ER PT J AU Hao, JJ Wang, GH Pisitkun, T Patino-Lopez, G Nagashima, K Knepjper, MA Shen, RF Shaw, S AF Hao, Jian-Jiang Wang, Guanghui Pisitkun, Trairak Patino-Lopez, Genaro Nagashima, Kunio Knepjper, Mark A. Shen, Rong-Fong Shaw, Stephen TI Enrichment of distinct microfilament-associated and GTP-binding-proteins in membrane/microvilli fractions from lymphoid cells SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE lymphocyte; microvillus; proteome; LC-MS/MS; label-free quatitation; cytoskeleton; small-GTP-binding protein; Myo1G; NHERF1; cofilin ID ERM FAMILY-MEMBERS; MASS-SPECTROMETRY; BRUSH-BORDER; PLACENTAL MICROVILLI; L-SELECTIN; PLASMA-MEMBRANE; T-LYMPHOCYTES; INNER-EAR; IN-VIVO; ACTIN AB Lymphocyte microvilli mediate initial adhesion to endothelium during lymphocyte transition from blood into tissue but their molecular organization is incompletely understood. We modified a shear-based procedure to prepare biochemical fractions enriched for membrane/microvilli (MMV) from both human peripheral blood T-lymphocytes (PBT) and a mouse pre-B lymphocyte line (300.19). Enrichment of proteins in MMV relative to post nuclear lysate was determined by LC/MS/MS analysis and label-free quantitation. Subsequent analysis emphasized the 291 proteins shared by PBT and 300.19 and estimated by MS peak area to be highest abundance. Validity of the label-free quantitation was confirmed by many internal consistencies and by comparison with Western blot analyses. The MMV fraction was enriched primarily for subsets of cytoskeletal proteins, transmembrane proteins and G-proteins, with similar patterns in both lymphoid cell types. The most enriched cytoskeletal proteins were microfilament-related proteins NHERF1, Ezrin/Radixin/Moesin (ERMs), ADF/cofilin and Myosin1G. Other microfilament proteins such as talin, gelsolin, myosin II and profilin were markedly reduced in MMV, as were intermediate filament- and microtubule-related proteins. Heterotrimeric G-proteins and some small G-proteins (especially Ras and Rap1) were enriched in the MMV preparation. Two notable general observations also emerged. There was less overlap between the two cells in their transmembrane proteins than in other classes of proteins, consistent with a special role of plasma membrane proteins in differentiation. Second, unstimulated primary T-lymphocytes have an unusually high concentration of actin and other microfilament related proteins, consistent with the singular role of actin-mediated motility in the immunological surveillance performed by these primary cells. C1 [Hao, Jian-Jiang; Patino-Lopez, Genaro; Shaw, Stephen] NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. [Wang, Guanghui; Shen, Rong-Fong] NIH, Bethesda, MD 20892 USA. [Pisitkun, Trairak; Knepjper, Mark A.] NHLBI, Lab Kidney & Elect Metab, NIH, Bethesda, MD 20892 USA. [Nagashima, Kunio] SAIC Frederick, Image Anal Lab, Frederick, MD 21702 USA. RP Shaw, S (reprint author), NCI, Expt Immunol Branch, Bldg 10, Bethesda, MD 20892 USA. EM ssliaw@nih.gov OI Pisitkun, Trairak/0000-0001-6677-2271; Patino-Lopez, Genaro/0000-0002-8716-722X FU Intramural NIH HHS [Z01 BC009257-31, Z01 HL001285-21, Z99 CA999999, Z99 HL999999]; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 80 TC 17 Z9 19 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD JUL PY 2008 VL 7 IS 7 BP 2911 EP 2927 DI 10.1021/pr800016a PG 17 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 323MF UT WOS:000257449500032 PM 18505283 ER PT J AU Ruttenberg, BE Pisitkun, T Knepper, MA Hoffert, JD AF Ruttenberg, Brian E. Pisitkun, Trairak Knepper, Mark A. Hoffert, Jason D. TI PhosphoScore: An open-source phosphorylation site assignment tool for MSn data SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE mass spectrometry; neutral loss; cost function ID QUANTITATIVE PHOSPHOPROTEOMICS; SIGNALING NETWORKS; MASS-SPECTROMETRY; PATHWAY AB Correct phosphorylation site assignment is a critical aspect of phosphoproteomic analysis. Large-scale phosphopeptide data sets that are generated through liquid chromatography-coupled tandem mass spectrometry (LC-MS/MS) analysis often contain hundreds or thousands of phosphorylation sites that require validation. To this end, we have created PhosphoScore, an open-source assignment program that is compatible with phosphopeptide data from multiple MS levels (MSn). The algorithm takes into account both the match quality and normalized intensity of observed spectral peaks compared to a theoretical spectrum. PhosphoScore produced >95% correct MS2 assignments from known synthetic data, > 98% agreement with an established MS2 assignment algorithm (Ascore), and >92% agreement with visual inspection of MS3 and MS4 spectra. C1 [Ruttenberg, Brian E.; Pisitkun, Trairak; Knepper, Mark A.; Hoffert, Jason D.] NHLBI, Lab Kidney & Elect Metab, Bethesda, MD 20892 USA. RP Hoffert, JD (reprint author), NIH Bldg 10,Room 6N260,10 Ctr Dr MSC 1603, Bethesda, MD 20892 USA. EM hoffertj@nhlbi.nih.gov OI Pisitkun, Trairak/0000-0001-6677-2271 FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NHLBI NIH HHS [Z01 HL001285, Z01-HL001285] NR 15 TC 60 Z9 64 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD JUL PY 2008 VL 7 IS 7 BP 3054 EP 3059 DI 10.1021/pr800169k PG 6 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 323MF UT WOS:000257449500046 PM 18543960 ER PT J AU Andreeva, VA Reynolds, KD Buller, DB Chou, CP Yaroch, AL AF Andreeva, Valentina A. Reynolds, Kim D. Buller, David B. Chou, Chih-Ping Yaroch, Amy L. TI Concurrent psychosocial predictors of sun safety among middle school youth SO JOURNAL OF SCHOOL HEALTH LA English DT Article DE adolescents; sun safety; psychosocial factors; structural equation models ID SKIN-CANCER PREVENTION; MEASUREMENT INVARIANCE; PROTECTION BEHAVIORS; MALIGNANT-MELANOMA; ADOLESCENTS; CHILDREN; ATTITUDES; EXPOSURE; RADIATION; KNOWLEDGE AB BACKGROUND: Sun-induced skin damage, which increases skin cancer risk, is initiated in early life and promoted through later sun exposure patterns. If sun safety determinants are well understood and addressed during the school years, skin cancer incidence might be reduced. This study tested psychosocial influences on youth's sun safety and assessed their strength within and across gender and ethnicity in a sample of 1782 middle school students. METHODS: Predictors included sunburn and skin cancer knowledge, tanning attitudes, peer norms, and barriers regarding sun exposure and were assessed with a self-administered, validated questionnaire. The hypothesized relationships were tested with structural equation models and confirmed with multilevel regression. RESULTS: Across gender and ethnicity, knowledge emerged as an important sun safety predictor with both direct and indirect effects mediated through tanning attitudes. The relationship with barriers did not reach statistical significance within any of the subgroups, possibly due to measurement limitations. An indirect effect of peer norms on sun safety, mediated through tanning attitudes, was confirmed only among girls. Also, an indication that peer norms operate differently within the ethnic groups was found, since this predictor had a statistically significantly stronger relationship with sun safety among non-Hispanics. CONCLUSIONS: Youth's sun safety is a multifactorial practice, partially determined by ethnicity- and gender-based standards. In order to ensure health-promoting school environments, needed are multicomponent programs where peer norms and knowledge are salient and where sun safety is addressed individually and together with other health risk behaviors. C1 [Andreeva, Valentina A.; Reynolds, Kim D.; Chou, Chih-Ping] Univ So Calif, Inst Hlth Promot & Dis Prevent Res, Keck Sch Med, Dept Prevent Med, Alhambra, CA 91803 USA. [Buller, David B.] Klein Buendel Inc, Golden, CO 80401 USA. [Yaroch, Amy L.] Natl Canc Inst, Hlth Promot Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Andreeva, VA (reprint author), Univ So Calif, Inst Hlth Promot & Dis Prevent Res, Keck Sch Med, Dept Prevent Med, 1000 S Fremont Ave, Alhambra, CA 91803 USA. EM andreeva@usc.edu; kdreynol@usc.edu; dbuller@kleinbuendel.com; cchou@usc.edu; yarocha@mail.nih.gov RI David, Maribel/E-2812-2012 FU NCI NIH HHS [R01 CA081864-05, CA81864, R01 CA081864, R01 CA081864-01A1, R01 CA081864-02, R01 CA081864-03, R01 CA081864-04, R01 CA081864-04S1, R01 CA081864-05S1] NR 37 TC 7 Z9 8 U1 2 U2 10 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-4391 J9 J SCHOOL HEALTH JI J. Sch. Health PD JUL PY 2008 VL 78 IS 7 BP 374 EP 381 DI 10.1111/j.1746-1561.2008.00317.x PG 8 WC Education & Educational Research; Education, Scientific Disciplines; Health Care Sciences & Services; Public, Environmental & Occupational Health SC Education & Educational Research; Health Care Sciences & Services; Public, Environmental & Occupational Health GA 316SX UT WOS:000256971100003 PM 18611212 ER PT J AU Willner-Reid, J Belendiuk, KA Epstein, DH Schmittner, J Preston, KL AF Willner-Reid, Jessica Belendiuk, Katherine A. Epstein, David H. Schmittner, John Preston, Kenzie L. TI Hepatitis C and human immunodeficiency virus risk behaviors in polydrug users on methadone maintenance SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE hepatitis C; risk behaviors; methadone maintenance; injection drug use; substance abuse ID INJECTING DRUG-USERS; NEW-YORK-CITY; HIV RISK; TAKING BEHAVIOR; INFECTION; PREVALENCE; PREVENTION; SEROCONVERSION; ASSOCIATION; REDUCTION AB We examined the impact of methadone maintenance treatment (MMT) on risk behaviors for transmission of blood-borne diseases in polydrug users who had tested positive or negative for hepatitis C virus (HCV). At intake, HCV-positive participants (n = 362) engaged in more human immunodeficiency virus (HIV) risk behaviors (as measured by the HIV Risk-Taking Behavior Scale) than HCV-negative participants (n = 297; p <.001). This difference was specific to injection-related behaviors and decreased significantly within the first few weeks of MMT (p <.0001). Where needles continued to be used, HCV-positive participants became more likely over time to engage in safer injecting practices. Furthermore, HCV-positive participants became more likely to use condoms than HCV-negative participants. These findings demonstrate that both drug- and sex-related risk behaviors decrease during MMT and emphasize the benefits of methadone programs for public health and HIV/HCV prevention. Published by Elsevier Inc. C1 [Preston, Kenzie L.] Natl Inst Drug Abuse, Intramural Res Program, Clin Pharmacol & Therapeut Res Branch, Baltimore, MD 21224 USA. [Belendiuk, Katherine A.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. RP Preston, KL (reprint author), Natl Inst Drug Abuse, Intramural Res Program, Clin Pharmacol & Therapeut Res Branch, Baltimore, MD 21224 USA. EM kpreston@intra.nida.nih.gov RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 FU Intramural NIH HHS [Z01 DA000175-13, Z01 DA000231-14] NR 47 TC 15 Z9 17 U1 1 U2 1 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 JUL PY 2008 VL 35 IS 1 BP 78 EP 86 DI 10.1016/j.jsat.2007.08.01 PG 9 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 313JV UT WOS:000256737800010 PM 17931826 ER PT J AU Stewart, SE Rosario, MC Baer, L Carter, AS Brown, TA Scharf, JM Illmann, C Leckman, JF Sukhodolsky, D Katsovich, L Rasmussen, S Goodman, W Delorme, R Leboyer, M Chabane, N Jenike, MA Geller, DA Pauls, DL AF Stewart, S. Evelyn Rosario, Maria C. Baer, Lee Carter, Alice S. Brown, Timothy A. Scharf, Jeremiah M. Illmann, Cornelia Leckman, James F. Sukhodolsky, Denis Katsovich, Lilya Rasmussen, Steven Goodman, Wayne Delorme, Richard Leboyer, Marion Chabane, Nadia Jenike, Michael A. Geller, Daniel A. Pauls, David L. TI Four-factor structure of obsessive-compulsive disorder symptoms in children, adolescents, and adults SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE obsessive-compulsive disorder; age; factor analysis; symptom dimension; quantitative trait ID MISCELLANEOUS SYMPTOMS; PERSONALITY-DISORDERS; YOUNG-CHILDREN; DIMENSIONS; FAMILIALITY; PHENOTYPES; SCALE; OCD; STABILITY; GENETICS AB Objective: To determine whether the four-factor category-based obsessive-compulsive disorder (OCD) symptom structure from a previous confirmatory factor analysis (CFA) may be appropriately used in child, adolescent, and adult groups. Symptom dimensions are increasingly used as quantitative traits in genetic, neuroimaging, and treatment studies of OCD across all ages. Identification of a category-based OCD symptom dimension structure that is validated for use across child, adolescent, and adult age groups is necessary to guide ongoing translational research. Method: Four OCD samples comprising 356 individuals were divided into child, adolescent, and adult groups. The fit of the only CFA-defined four-factor model was compared across these independent age group samples. Multiple-group CFA using maximum likelihood estimation assessed adequacy of fit comparing unconstrained and measurement weight-constrained models. The fit of previous exploratory factor analysis-defined three- and five-factor models on adults was also examined using CFA. Results: A four-factor solution provided adequate but imperfect fit across age groups, with comparable indices to the only previous OCD CFA: factor 1 (aggressive/sexual/religious/somatic/checking); factor 2 (symmetry/ordering/counting/ repeating); factor 3 (contamination/cleaning), and factor 4 (hoarding). Models in which factor loadings were constrained and unconstrained across the three age groups yielded comparable model fit. Factors were highly correlated and were not mutually exclusive. The four-factor solution provided an improved fit to both three- and five-factor solutions using CFA across the three age groups. Conclusions: A four-factor, CFA-defined, category-based model of OCD symptom dimensions is adequate for use in children, adolescents, and adult age groups. The factor structure of this multiple age group sample has limitations and is imperfect, but current findings support the comparability of the defined latent OCD dimensions across age groups. Further work is needed to optimize a comprehensive symptom dimension model reflecting clinical heterogeneity for use in emergent translational studies. C1 [Stewart, S. Evelyn; Baer, Lee; Scharf, Jeremiah M.; Illmann, Cornelia; Geller, Daniel A.; Pauls, David L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rosario, Maria C.] Univ Fed Sao Paulo, Sao Paulo, Brazil. [Brown, Timothy A.] Boston Univ, Boston, MA 02215 USA. [Leckman, James F.; Sukhodolsky, Denis; Katsovich, Lilya] Yale Univ, New Haven, CT 06520 USA. [Carter, Alice S.] Univ Massachusetts, Amherst, MA 01003 USA. [Rasmussen, Steven] Brown Univ, Providence, RI 02912 USA. [Goodman, Wayne] Natl Inst Hlth, Bethesda, MD 20892 USA. [Delorme, Richard; Chabane, Nadia] Hop Robert Debre, F-75019 Paris, France. [Leboyer, Marion] Mondor Chenevier Hosp, Creteil, France. RP Pauls, DL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 185 Cambridge St, Boston, MA 02114 USA. EM pauls@pngu.mgh.harvard.edu RI Stewart, Evelyn/K-6961-2014; do Rosario, Maria Conceicao/E-5213-2012; OI do Rosario, Maria Conceicao/0000-0002-9687-0072; Sukhodolsky, Denis/0000-0002-5401-792X; Stewart, S. Evelyn/0000-0002-0994-6383 FU NIMH NIH HHS [K08-MH01481, MH49351]; NINDS NIH HHS [R01-NS16648] NR 48 TC 48 Z9 49 U1 2 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUL PY 2008 VL 47 IS 7 BP 763 EP 772 DI 10.1097/CHI.0b013e318172ef1e PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 319HC UT WOS:000257153700007 PM 18520961 ER PT J AU Acosta, MT Castellanos, FX Bolton, KL Balog, JZ Eagen, P Nee, L Jones, J Palacio, L Sarampote, C Russell, HF Berg, K Arcos-Burgos, M Muenke, M AF Acosta, Maria T. Castellanos, F. Xavier Bolton, Kelly L. Balog, Joan Z. Eagen, Patricia Nee, Linda Jones, Janet Palacio, Luis Sarampote, Christopher Russell, Heather F. Berg, Kate Arcos-Burgos, Mauricio Muenke, Maximilian TI Latent class subtyping of attention-deficit/hyperactivity disorder and comorbid conditions SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit/hyperactivity disorder; latent class analysis; comorbidity; genetics ID DEFICIT HYPERACTIVITY DISORDER; OPPOSITIONAL DEFIANT DISORDER; DSM-IV ADHD; DIAGNOSTIC INTERVIEW; DYSTHYMIC DISORDER; POPULATION-SAMPLE; FAMILIAL SUBTYPE; RATING-SCALE; CHILDREN; ADOLESCENTS AB Objective: Genetic studies of attention-deficit/hyperactivity disorder (ADHD) generally use discrete DSM-IV subtypes to define diagnostic status. To improve correspondence between phenotypic variance and putative susceptibility genes, multivariate classification methods such as latent class analysis (LCA) have been proposed. The aim of this study was to perform LCA in a sample of 1,010 individuals from a nationwide recruitment of unilineal nuclear families with at least one child with ADHD and another child either affected or clearly unaffected. Method: LCA models containing one through 10 classes were fitted to data derived from all DSM-IV symptoms for ADHD, oppositional defiant disorder, and conduct disorder (CD), as well as seven items that screen for anxiety and depression from the National Initiative for Children's Healthcare Quality Vanderbilt Assessment Scale for Parents. Results: We replicated six to eight statistically significantly distinct clusters, similar to those described in other cross-cultural studies, mostly stable when comorbidities are included. For all age groups, anxiety and depression are strongly related to Inattentive and Combined types. Externalizing symptoms, especially CD, are strongly associated with the Combined type of ADHD. Oppositional defiant disorder symptoms in young children are associated with either conduct disorder or anxiety-related symptoms. Conclusions: Methods such as LCA allow inclusion of information about comorbidities to be quantitatively incorporated into genetic studies. LCA also permits incorporation of milder but still impairing phenotypes than are allowed using the DSM-IV. Such methods may be essential for analyses of large multicenter datasets and relevant for future clinical classifications. This population-based ADHD classification may help resolve the contradictory results presented in molecular genetic studies. C1 [Acosta, Maria T.; Bolton, Kelly L.; Balog, Joan Z.; Eagen, Patricia; Nee, Linda; Jones, Janet; Palacio, Luis; Sarampote, Christopher; Russell, Heather F.; Berg, Kate; Arcos-Burgos, Mauricio; Muenke, Maximilian] NHGRI, NIH, Med Genet Branch, Bethesda, MD 20892 USA. [Castellanos, F. Xavier] NYU, Ctr Child Study, New York, NY 10003 USA. RP Muenke, M (reprint author), NHGRI, NIH, Med Genet Branch, 35 Convent Dr,MSC 3717,Bldg 35,Room 1B-203, Bethesda, MD 20892 USA. EM mmuenke@nhgri.nih.gov OI Castellanos, Francisco/0000-0001-9192-9437 FU Intramural NIH HHS [Z99 HG999999] NR 55 TC 43 Z9 43 U1 8 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUL PY 2008 VL 47 IS 7 BP 797 EP 807 DI 10.1097/CHI.0b013e318173f70b PG 11 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 319HC UT WOS:000257153700011 PM 18520958 ER PT J AU Gozalo, AS Maximova, OA StClaire, MC Montali, RJ Ward, JM Cheng, LI Elkins, WR Kazacos, KR AF Gozalo, Alfonso S. Maximova, Olga A. StClaire, Marisa C. Montali, Richard J. Ward, Jerrold M. Cheng, Lily I. Elkins, William R. Kazacos, Kevin R. TI Visceral and neural larva migrans in rhesus macaques SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Article ID BAYLISASCARIS-PROCYONIS; CEREBROSPINAL NEMATODIASIS; TOXASCARIS; COLONY AB Large ascarid larvae within granulomas were noted histologically in the mesenteric and pancreatic lymph nodes of 13 of 21 rhesus macaques (Macaca mulatta) euthanized as part of an experimental viral pathogenesis study. In addition, 7 of the 13 monkeys had cerebral granulomas, which in 4 animals contained nematode larvae similar to those within the lymph nodes. Despite the lesions, the animals did not show clinical signs associated with the parasitic infections. Characteristics of the larvae included, on cross-section, a midbody diameter of approximately 60 to 80 pm, a centrally located and slightly compressed intestine flanked on either side by large triangular excretory columns, and prominent single lateral cuticular alae. The morphology of the larvae was compatible with Baylisascaris spp. Baylisascariasis is a well-described infection of animals and humans that is caused by migrating larvae of the raccoon roundworm, Baylisascaris procyonis. A similar species, B. columnaris, is found in skunks and can cause cerebrospinal nematodiasis, but most reported cases of baylisascariasis have been due to B. procyonis. Our macaques were born free-ranging on an island in the southeastern United States where raccoons, but not skunks, were found to be common inhabitants, indicating that B. procyonis m as the most likely parasite involved. These cases are similar to the low-level or covert cases of Baylisascaris infection described to occur in humans and provide further evidence of the existence of this parasite in the southeastern United States. C1 [Gozalo, Alfonso S.; Montali, Richard J.; Ward, Jerrold M.; Cheng, Lily I.; Elkins, William R.] NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA. [Gozalo, Alfonso S.; Montali, Richard J.; Ward, Jerrold M.; Cheng, Lily I.] Sobran Incorp, Bethesda, MD USA. [Maximova, Olga A.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [StClaire, Marisa C.] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA. [Kazacos, Kevin R.] Purdue Univ, Dept Comparat Pathobiol, W Lafayette, IN 47907 USA. RP Gozalo, AS (reprint author), NIAID, Comparat Med Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM gozaloa@niaid.nih.gov FU Intramural NIH HHS NR 18 TC 5 Z9 7 U1 0 U2 3 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD JUL PY 2008 VL 47 IS 4 BP 64 EP 67 PG 4 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 334CH UT WOS:000258199400009 PM 18702454 ER PT J AU Gozalo, AS Montoya, EJ Weller, RE AF Gozalo, Alfonso S. Montoya, Enrique J. Weller, Richard E. TI Dyscoria associated with herpesvirus infection in owl monkeys (Aotus nancymae) SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Article ID SIMPLEX-VIRUS; TRIVIRGATUS; ENCEPHALITIS; CAPTIVITY; TYPE-1 AB Dyscoria was noted in a female owl monkey and 2 of her offspring. The third offspring was found dead with necrohemorrhagic encephalitis. Two male monkeys paired with the female died, 1 of which showed oral ulcers at necropsy. Histologic examination of the oral ulcers revealed syncytia and eosinophilic intranuclear inclusion bodies in epithelial cells. Ocular examination revealed posterior synechia associated with the dyscoria in all 3 animals. Serum samples from the female and her offspring were positive for Herpesvirus simplex antibodies by ELISA. The clinical history, gross and microscopic lesions, and serology results suggests a herpesviral etiology, possibly H. simplex or H. saimiri 1. This report underscores the risks associated with introducing into breeding or research colonies animals that previously were kept as pets or those from unknown origin that could carry asymptomatic pathogenic Herpesvirus infections. In addition, herpesviral infection should be considered among the differential diagnoses if dyscoria is noted in nonhuman primates. C1 [Gozalo, Alfonso S.] Sobran Incorp, Bethesda, MD USA. [Gozalo, Alfonso S.; Montoya, Enrique J.] Univ Nacl Mayor San Marcos, Fac Med Vet, Inst Vet Invest Trop & Altura, Iquitos, Peru. RP Gozalo, AS (reprint author), NIAID, Comparat Med Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM gozaloa@niaid.nih.gov FU Peruvian Government; the Pan American Health Organization [ICF/ZNS/010]; the Intramural Research Program of the National Institutes of Health; National Institute of Allergy and Infectious Diseases (NIAID); Comparative Medicine Branch; the Office of Research Support; NIAID contract to SoBran Inc FX This study was conducted as part of the activities of the Peruvian Primatological Project, supported by the Peruvian Government and the Pan American Health Organization (ICF/ZNS/010), and by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIAID), Comparative Medicine Branch, the Office of Research Support, and a NIAID contract to SoBran Inc. We want to thank Dr Hugo Samame, Dr Gerald Dagle, Mr Arnulfo Romaina, and Mr Jarvel Lopez for laboratory and diagnostic support and Dr Jerrold Ward, Dr Lily Cheng, and Dr Carmen Michaud for photographic assistance. This study was presented at the 30th annual workshop of the Association of Primate Veterinarians in Boerne, Texas, 2002. NR 16 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD JUL PY 2008 VL 47 IS 4 BP 68 EP 71 PG 4 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 334CH UT WOS:000258199400010 PM 18702455 ER PT J AU Keselman, A Logan, R Smith, CA Leroy, G Zeng-Treitler, Q AF Keselman, Alla Logan, Robert Smith, Catherine Arnott Leroy, Gondy Zeng-Treitler, Qing TI Developing Informatics tools and strategies for consumer-centered health communication SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID WORLD-WIDE-WEB; CANCER INFORMATION; MANAGING FEVER; BREAST-CANCER; LITERACY; INTERNET; QUALITY; CARE; RETRIEVAL; USABILITY AB As the emphasis on individuals' active partnership in health care grows, so does the public's need for effective, comprehensible consumer health resources. Consumer health informatics has the potential to provide frameworks and strategies for designing effective health communication tools that empower users and improve their health decisions. This article presents an overview of the consumer health informatics field, discusses promising approaches to supporting health communication, and identifies challenges plus direction for future research and development. The authors' recommendations emphasize the need for drawing upon communication and social science theories of information behavior, reaching out to consumers via a range of traditional and novel formats, gaining better understanding of the public's health information needs, and developing informatics solutions for tailoring resources to users' needs and competencies. This article was written as a scholarly outreach and leadership project by members of the American Medical Informatics Association's Consumer Health Informatics Working Group. C1 [Keselman, Alla] NIH, Div Specialized Informat Serv, Natl Lib Med, Bethesda, MD 20892 USA. [Logan, Robert] NIH, Off Commun & Publ Liaison, Natl Lib Med, Bethesda, MD 20892 USA. [Keselman, Alla] Aquilent Inc, Laurel, MD USA. [Smith, Catherine Arnott] Univ Wisconsin, Sch Lib & Informat Studies, Madison, WI 53706 USA. [Leroy, Gondy] Claremont Grad Univ, Sch Informat Syst & Technol, Claremont, CA USA. [Zeng-Treitler, Qing] Harvard Univ, Sch Med, Decis Syst Grp, Boston, MA USA. RP Keselman, A (reprint author), 2 Democracy Plaza,Suite 510,6707 Democracy Blvd, Bethesda, MD 20892 USA. EM keselmana@mail.nih.gov FU Intramural NIH HHS; NIDDK NIH HHS [R01 DK75837, R01 DK075837]; NLM NIH HHS [R01 LM007222, R01 LM07222, R21 LM008860] NR 77 TC 41 Z9 42 U1 3 U2 24 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JUL-AUG PY 2008 VL 15 IS 4 BP 473 EP 483 DI 10.1197/jamia.M2744 PG 11 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 328JM UT WOS:000257794700011 PM 18436895 ER PT J AU Keselman, A Browne, AC Kaufman, DR AF Keselman, Alla Browne, Allen C. Kaufman, David R. TI Consumer health information seeking as hypothesis testing SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID INTERNET; RETRIEVAL; USABILITY; KNOWLEDGE; FRAMEWORK; PATIENT; SEARCH; BIASES; WORLD; WEB AB Objective: Despite the proliferation of consumer health sites, lay individuals often experience difficulty finding health information online. The present study attempts to understand users' information seeking difficulties by drawing on a hypothesis testing explanatory framework. It also addresses the role of user competencies and their interaction with internet resources. Design: Twenty participants were interviewed about their understanding of a hypothetical scenario about a family member suffering from stable angina and then searched MedlinePlus (R) consumer health information portal for information on the problem presented in the scenario. Participants' understanding of heart disease was analyzed via semantic analysis. Thematic coding was used to describe information seeking trajectories in terms of three key strategies: verification of the primary hypothesis, narrowing search within the general hypothesis area and bottom-up search. Results: Compared to an expert model, participants' understanding of heart disease involved different key concepts, which were also differently grouped and defined. This understanding provided the framework for search-guiding hypotheses and results interpretation. Incorrect or imprecise domain knowledge led individuals to search for information on irrelevant sites, often seeking out data to confirm their incorrect initial hypotheses. Online search skills enhanced search efficiency, but did not eliminate these difficulties. Conclusions: Regardless of their web experience and general search skills, lay individuals may experience difficulty with health information searches. These difficulties may be related to formulating and evaluating hypotheses that are rooted in their domain knowledge. Informatics can provide support at the levels of health information portals, individual websites, and consumer education tools. C1 [Keselman, Alla; Browne, Allen C.] NIH, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20892 USA. [Keselman, Alla] Aquilent Inc, Laurel, MD USA. [Kaufman, David R.] Columbia Univ, Dept Biomed Informat, New York, NY USA. RP Keselman, A (reprint author), NLM NIH, Specialized Informat Serv, 2 Democracy Plaza,Suite 510,6707 Democracy Blvd,M, Bethesda, MD 20892 USA. EM keselmana@mail.nih.gov RI Norfadzila, Syarifah/G-9607-2012 FU Intramural NIH HHS; NLM NIH HHS [1R01LM008799-01A1, R01 LM008799] NR 40 TC 45 Z9 45 U1 3 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JUL-AUG PY 2008 VL 15 IS 4 BP 484 EP 495 DI 10.1197/jamia.M2449 PG 12 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 328JM UT WOS:000257794700012 PM 18436912 ER PT J AU Keselman, A Smith, CA Divita, G Kim, H Browne, AC Leroy, G Zeng-Treitler, Q AF Keselman, Alla Smith, Catherine Arnott Divita, Guy Kim, Hyeoneui Browne, Allen C. Leroy, Gondy Zeng-Treitler, Qing TI Consumer health concepts that do not map to the UMLS: Where do they fit? SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID VOCABULARIES; PATIENT; DOCTOR; WORDS AB Objective: This study has two objectives: first, to identify and characterize consumer health terms not found in the Unified Medical Language System (UMLS) Metathesaurus (2007 AB); second, to describe the procedure for creating new concepts in the process of building a consumer health vocabulary. How do the unmapped consumer health concepts relate to the existing UMLS concepts? What is the place of these new concepts in professional medical discourse? Design: The consumer health terms were extracted from two large corpora derived in the process of Open Access Collaboratory Consumer Health Vocabulary (OAC CHV) building. Terms that could not be mapped to existing UMLS concepts via machine and manual methods prompted creation of new concepts, which were then ascribed semantic types, related to existing UMLS concepts, and coded according to specified criteria. Results: This approach identified 64 unmapped concepts, 17 of which were labeled as uniquely "lay" and not feasible for inclusion in professional health terminologies. The remaining terms constituted potential candidates for inclusion in professional vocabularies, or could be constructed by post-coordinating existing UMLS terms. The relationship between new and existing concepts differed depending on the corpora from which they were extracted. Conclusion: Non-mapping concepts constitute a small proportion of consumer health terms, but a proportion that is likely to affect the process of consumer health vocabulary building. We have identified a novel approach for identifying such concepts. C1 [Keselman, Alla; Divita, Guy; Browne, Allen C.] NIH, LHNCBC, Natl Lib Med, Bethesda, MD 20892 USA. [Keselman, Alla] Aquilent Inc, Laurel, MD USA. [Smith, Catherine Arnott] Univ Wisconsin, Sch Lib & Informat Studies, Madison, WI USA. [Divita, Guy] Lockheed Martin Inc, Bethesda, MD USA. [Kim, Hyeoneui; Zeng-Treitler, Qing] Harvard Univ, Sch Med, Brigham & Womens Hosp, Decis Syst Grp, Boston, MA USA. Claremont Grad Sch, Sch Informat Syst & Technol, Claremont, CA 91711 USA. RP Keselman, A (reprint author), NIH, LHNCBC, Natl Lib Med, 7S713E,8600 Rockville Pike, Bethesda, MD 20892 USA. EM keselmana@mail.nih.gov FU Intramural NIH HHS; NLM NIH HHS [R01 LM007222, R01 LM07222] NR 22 TC 19 Z9 19 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JUL-AUG PY 2008 VL 15 IS 4 BP 496 EP 505 DI 10.1197/jamia.M2599 PG 10 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 328JM UT WOS:000257794700013 PM 18436906 ER EF